US20230390187A1 - Needle assisted jet injection administration of testosterone compositions - Google Patents
Needle assisted jet injection administration of testosterone compositions Download PDFInfo
- Publication number
- US20230390187A1 US20230390187A1 US18/452,743 US202318452743A US2023390187A1 US 20230390187 A1 US20230390187 A1 US 20230390187A1 US 202318452743 A US202318452743 A US 202318452743A US 2023390187 A1 US2023390187 A1 US 2023390187A1
- Authority
- US
- United States
- Prior art keywords
- needle
- medicament
- testosterone
- injection
- injection device
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 title claims abstract description 479
- 229960003604 testosterone Drugs 0.000 title claims abstract description 233
- 238000002347 injection Methods 0.000 title claims abstract description 218
- 239000007924 injection Substances 0.000 title claims abstract description 218
- 239000000203 mixture Substances 0.000 title abstract description 89
- 239000003814 drug Substances 0.000 claims description 194
- 229940090047 auto-injector Drugs 0.000 claims description 42
- 238000007920 subcutaneous administration Methods 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 10
- 230000004913 activation Effects 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 230000001681 protective effect Effects 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 56
- 238000011282 treatment Methods 0.000 abstract description 7
- 230000036470 plasma concentration Effects 0.000 description 68
- 238000009472 formulation Methods 0.000 description 33
- 241001465754 Metazoa Species 0.000 description 22
- 229940090046 jet injector Drugs 0.000 description 22
- 229940071643 prefilled syringe Drugs 0.000 description 20
- 230000007246 mechanism Effects 0.000 description 19
- 238000012360 testing method Methods 0.000 description 19
- VOCBWIIFXDYGNZ-IXKNJLPQSA-N testosterone enanthate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCC)[C@@]1(C)CC2 VOCBWIIFXDYGNZ-IXKNJLPQSA-N 0.000 description 18
- 229960003484 testosterone enanthate Drugs 0.000 description 18
- 210000002966 serum Anatomy 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 17
- 239000012530 fluid Substances 0.000 description 14
- 239000000463 material Substances 0.000 description 14
- 238000010438 heat treatment Methods 0.000 description 13
- 230000033001 locomotion Effects 0.000 description 13
- 239000003755 preservative agent Substances 0.000 description 13
- 241000124008 Mammalia Species 0.000 description 12
- 230000007423 decrease Effects 0.000 description 11
- 210000002381 plasma Anatomy 0.000 description 11
- 238000007918 intramuscular administration Methods 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 235000019198 oils Nutrition 0.000 description 10
- 230000002335 preservative effect Effects 0.000 description 10
- 239000008159 sesame oil Substances 0.000 description 10
- 235000011803 sesame oil Nutrition 0.000 description 10
- 244000309715 mini pig Species 0.000 description 9
- 230000004936 stimulating effect Effects 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 239000003937 drug carrier Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 238000010304 firing Methods 0.000 description 8
- 210000002414 leg Anatomy 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000000499 gel Substances 0.000 description 7
- 238000010255 intramuscular injection Methods 0.000 description 7
- 239000007927 intramuscular injection Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000007906 compression Methods 0.000 description 6
- 230000006835 compression Effects 0.000 description 6
- 238000010276 construction Methods 0.000 description 6
- 230000035515 penetration Effects 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 5
- 229920001971 elastomer Polymers 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 238000010254 subcutaneous injection Methods 0.000 description 5
- 239000007929 subcutaneous injection Substances 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 229940051104 testim Drugs 0.000 description 5
- -1 testosterone Chemical class 0.000 description 5
- 244000105624 Arachis hypogaea Species 0.000 description 4
- 206010058359 Hypogonadism Diseases 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- 235000003911 Arachis Nutrition 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 229940001610 axiron Drugs 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 210000003141 lower extremity Anatomy 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000002028 premature Effects 0.000 description 3
- 239000005060 rubber Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 239000011345 viscous material Substances 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 238000012800 visualization Methods 0.000 description 3
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- 208000010228 Erectile Dysfunction Diseases 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 101600111816 Homo sapiens Sex hormone-binding globulin (isoform 1) Proteins 0.000 description 2
- 206010024870 Loss of libido Diseases 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102000007562 Serum Albumin Human genes 0.000 description 2
- 108010071390 Serum Albumin Proteins 0.000 description 2
- 102300044179 Sex hormone-binding globulin isoform 1 Human genes 0.000 description 2
- 241000282898 Sus scrofa Species 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- 238000005299 abrasion Methods 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 230000037058 blood plasma level Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 239000000806 elastomer Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 201000001881 impotence Diseases 0.000 description 2
- 208000000509 infertility Diseases 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 231100000535 infertility Toxicity 0.000 description 2
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 230000013011 mating Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000009964 serging Methods 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 229960000921 testosterone cypionate Drugs 0.000 description 2
- HPFVBGJFAYZEBE-ZLQWOROUSA-N testosterone cypionate Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(CCC(=O)C=C4CC3)C)CC[C@@]21C)C(=O)CCC1CCCC1 HPFVBGJFAYZEBE-ZLQWOROUSA-N 0.000 description 2
- 231100000607 toxicokinetics Toxicity 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 208000008601 Polycythemia Diseases 0.000 description 1
- 229920002700 Polyoxyl 60 hydrogenated castor oil Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 229940062331 androgel Drugs 0.000 description 1
- 102000001307 androgen receptors Human genes 0.000 description 1
- 108010080146 androgen receptors Proteins 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940067596 butylparaben Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 231100001030 dermal change Toxicity 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 231100000321 erythema Toxicity 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000012633 leachable Substances 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 239000002583 male contraceptive agent Substances 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 230000037368 penetrate the skin Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- VUXSPDNLYQTOSY-UHFFFAOYSA-N phenylmercuric borate Chemical compound OB(O)O[Hg]C1=CC=CC=C1 VUXSPDNLYQTOSY-UHFFFAOYSA-N 0.000 description 1
- 229960000247 phenylmercuric borate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 230000007943 positive regulation of appetite Effects 0.000 description 1
- 231100001271 preclinical toxicology Toxicity 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 238000007639 printing Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012858 resilient material Substances 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 125000006850 spacer group Chemical group 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 150000003515 testosterones Chemical class 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M37/00—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/002—Packages specially adapted therefor, e.g. for syringes or needles, kits for diabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
- A61M5/2033—Spring-loaded one-shot injectors with or without automatic needle insertion
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/30—Syringes for injection by jet action, without needle, e.g. for use with replaceable ampoules or carpules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/315—Pistons; Piston-rods; Guiding, blocking or restricting the movement of the rod or piston; Appliances on the rod for facilitating dosing ; Dosing mechanisms
- A61M5/31525—Dosing
- A61M5/3153—Dosing by single stroke limiting means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
- A61M5/3202—Devices for protection of the needle before use, e.g. caps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/32—Needles; Details of needles pertaining to their connection with syringe or hub; Accessories for bringing the needle into, or holding the needle on, the body; Devices for protection of needles
- A61M5/3205—Apparatus for removing or disposing of used needles or syringes, e.g. containers; Means for protection against accidental injuries from used needles
- A61M5/321—Means for protection against accidental injuries by used needles
- A61M5/3243—Means for protection against accidental injuries by used needles being axially-extensible, e.g. protective sleeves coaxially slidable on the syringe barrel
- A61M5/326—Fully automatic sleeve extension, i.e. in which triggering of the sleeve does not require a deliberate action by the user
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/42—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for desensitising skin, for protruding skin to facilitate piercing, or for locating point where body is to be pierced
- A61M5/425—Protruding skin to facilitate piercing, e.g. vacuum cylinders, vein immobilising means
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/44—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for cooling or heating the devices or media
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
- A61M2005/2006—Having specific accessories
- A61M2005/2013—Having specific accessories triggering of discharging means by contact of injector with patient body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
- A61M2005/206—With automatic needle insertion
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/20—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically
- A61M2005/2073—Automatic syringes, e.g. with automatically actuated piston rod, with automatic needle injection, filling automatically preventing premature release, e.g. by making use of a safety lock
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/36—General characteristics of the apparatus related to heating or cooling
- A61M2205/3613—General characteristics of the apparatus related to heating or cooling by body heat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/36—General characteristics of the apparatus related to heating or cooling
- A61M2205/364—General characteristics of the apparatus related to heating or cooling by chemical reaction
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M2205/00—General characteristics of the apparatus
- A61M2205/36—General characteristics of the apparatus related to heating or cooling
- A61M2205/3673—General characteristics of the apparatus related to heating or cooling thermo-electric, e.g. Peltier effect, thermocouples, semi-conductors
Definitions
- Testosterone is a steroid hormone from the androgen group. In general, androgens promote protein synthesis and growth of those tissues with androgen receptors. Testosterone is anabolic, meaning it builds up bone and muscle mass. Testosterone has the following structural formula:
- testosterone has also been given for many other conditions, e.g., reducing infertility, correcting lack of libido or erectile dysfunction, correcting osteoporosis, encouraging penile enlargement, encouraging height growth, encouraging bone marrow stimulation, reversing the effects of anemia and appetite stimulation.
- testosterone There are several application methods for testosterone, including hypodermic injections and transdermal creams, gels and patches.
- hypodermic injections tend to be painful, inconvenient, and increase the risk of polycythemia.
- Transdermal creams, gels and patches are often expensive, cause acne and skin irritation at the site of administration, have poor compliance with daily administration, and fail to provide some patients with adequate testosterone levels.
- the present invention includes an injection device, comprising a housing member having a distal end and a proximal end, a chamber disposed within the housing member configured to hold an amount of a preservative-free medicament comprising testosterone, a needle operatively associated with the chamber and having a length sufficient to deliver the medicament to an injection site at a depth below a patient's skin sufficient to minimize leak-back, a plunger movable within the chamber, and a force generating source capable of providing sufficient force on the plunger to eject at least a portion of the medicament from the chamber through the needle in less than about 20 seconds.
- the present invention includes a composition comprising testosterone enanthate and sesame oil, the testosterone enanthate being present at a concentration selected from the group consisting of about 50 mg/ml, about 75 mg/ml, about 100 mg/ml, about 125 mg/ml, about 150 mg/ml, about 175 mg/ml, about 200 mg/ml, about 225 mg/ml, and about 250 mg/ml.
- the present invention includes a composition comprising testosterone enanthate and sesame oil, the testosterone enanthate being present at a concentration selected from the group consisting of about 50 mg/ml, about 75 mg/ml, about 100 mg/ml, about 125 mg/ml, about 150 mg/ml, about 175 mg/ml, about 200 mg/ml, about 225 mg/ml, and about 250 mg/ml, wherein the composition is substantially free of testosterone enanthate precipitate.
- the present invention includes a method of administering testosterone comprising administering preservative-free composition comprising a unit dose of a testosterone or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration, the plasma level of testosterone is maintained between about 200 ng/dl and about 1800 ng/dl for a Z1 time period.
- the present invention includes method of administering testosterone comprising administering a preservative-free composition comprising a unit dose of testosterone or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained at a therapeutically effective level for a Z2 time period, (e.g., an extended period of time during treatment).
- FIG. 1 is a side view of an injection device according to an embodiment of the present disclosure
- FIG. 2 is a cross-sectional view of the injection device of FIG. 1 in a safety state taken along line A-A;
- FIG. 3 is an enlarged view of a portion of the cross-section shown in FIG. 2 ;
- FIGS. 4 A and 4 B are perspective views of a safety member used in connection with the injection device of FIG. 1 ;
- FIG. 5 is an additional cross-sectional view of the device of FIG. 1 in the safety state
- FIG. 6 A is a cross-sectional view of the injection device of FIG. 1 in a ready state
- FIG. 6 B is a cross-sectional view of the injection device of FIG. 1 at the start of an injection state
- FIG. 6 C is a cross-sectional view of the injection device of FIG. 1 at the end of an injection state
- FIG. 6 D is a cross-sectional view of the injection device of FIG. 1 in a locked state
- FIG. 7 is an exploded view of an assembly of the needle guard, sleeve and locking ring associated with the injection device of FIG. 1 ;
- FIG. 8 is a perspective view of a needle guard according to an embodiment of the injector of FIG. 1 ;
- FIG. 9 is a cross-sectional view of the cap shown in FIG. 1 ;
- FIG. 10 is a graph showing the pressure within the liquid chamber of an embodiment of an injection device according to the present disclosure, as a function of time;
- FIG. 11 is a cross-sectional view of a needle-free jet injection nozzle
- FIG. 12 is a graph illustrating an embodiment of the present disclosure in which serum testosterone demonstrates a peak upon injection and subsequently decreases to a therapeutically effective level
- FIG. 13 is a table illustrating the mean concentrations of testosterone in mini-pig serum
- FIG. 14 is graph illustrating the serum concentration of testosterone in the group 1 mini-pigs of FIG. 13 ;
- FIG. 15 is graph illustrating the serum concentration of testosterone in the group 2 mini-pigs of FIG. 13 ;
- FIG. 16 is graph illustrating the serum concentration of testosterone for a 0.5 ml auto-injector injection of 200 mg/ml testosterone enanthate in sesame oil;
- FIG. 17 is graph illustrating the serum concentration of testosterone for a 0.5 ml needle and syringe injection of 200 mg/ml testosterone enanthate in sesame oil;
- FIG. 18 is graph illustrating the serum concentration of testosterone for a 0.5 ml auto-injector injection of 100 mg/ml testosterone enanthate in sesame oil.
- FIG. 19 is graph illustrating the serum concentration of testosterone for a 0.5 ml needle and syringe injection of 100 mg/ml testosterone enanthate in sesame oil.
- Leak back refers to the leakage of medicament out of an injection site during and/or after injection of a medicament.
- substantially no leak back refers an amount of leak back from an injection, the amount being less than about 0.05 ml or less than about 6% of the total volume or less than about 6% of the weight of the medicament. In an embodiment, “substantially no leak back” is an amount of leak back at or below an amount that cannot be readily detected by swiping a finger across the site of injection immediately after the injection has been completed. In an embodiment, “substantially no leak back” is an amount of leak back such that the therapeutic effect of testosterone administered by the injection is not materially altered.
- the amount of leak back can be referenced in a liquid volume of a fluid composition having a specific concentration of testosterone, or the amount of leak back can be referred to in terms of amount of testosterone (e.g., mg testosterone) present in the total leak back volume or the number of injecting patients out of a population that experience leak back.
- amount of testosterone e.g., mg testosterone
- AUC is the area under a curve representing the concentration of a compound, such as testosterone, or metabolite thereof in the blood or plasma or serum of a patient as a function of time following administration of the compound to the patient.
- the AUC of the testosterone may be determined by measuring the concentration of it or its metabolite in blood using methods such as liquid chromatography-tandem mass spectrometry (LC-MS/MS), at various time intervals, and calculating the area under the blood, plasma or serum concentration-versus-time curve.
- the concentration versus time curve is sometime referred to as the pharmacokinetic profile. Suitable methods for calculating the AUC from a drug concentration-versus-time curve are well known in the art. Therefore, an AUC for testosterone may be determined by measuring the concentration of testosterone in the blood of a patient following administration of the testosterone to a patient.
- Bioavailability refers to the amount of a compound, such as testosterone, that reaches the systemic circulation of a patient following administration of the compound to the patient and can be determined by evaluating, for example, the blood or plasma concentration for the compound.
- Bioequivalent refers to one or more of confidence intervals of (a) the maximum concentration of a medicament (e.g., testosterone) in blood plasma of a patient following administration of a dose of the medicament to a patient (“Cmax”) with an injector, (b) the time to reach the maximum concentration of the medicament in blood plasma of a patient following administration of a dose of the medicament to the patient with an injector (“Tmax”), and (c) area under the curve of the concentration of the medicament in blood plasma of a patient following administration of a dose of the medicament to the patient with the injector injected medicament (“AUC”) falls between about 80% and about 125% of the measured confidence interval of the same medicament delivered by an alternative route.
- a medicament e.g., testosterone
- “About” is understood to mean the range of + and ⁇ 10% of the value referenced. However, use of “about” in reference to a value does not exclude the possibility of the referenced value alone. For example, “about 400” is understood to fully support both “400” as well as “360 to 440.”
- the present disclosure encompasses injector embodiments and compositions and methods suitable for use alone or in combination with the injector embodiments.
- Typical hypodermic syringes utilize the force of one or more of a user's fingers pushing to deliver an injection.
- powered injectors of the present disclosure are configured to help a subject repeatably and accurately and quickly administer a testosterone formulation to a preset depth at each injection without the need to utilize such pushing force.
- the powered injector includes an autoinjector, a needle-free jet injector, or a needle-assisted jet injector (collectively referred to as “injectors”).
- Powered injector embodiments of powered injectors use an energy source that produces moderate to low pressure in the medicament chamber so that a medicament contained in the medicament chamber is fired at a slow speed, similar to the pressure and speed from a finger-driven syringe.
- autoinjector embodiments of the powered injectors of the present disclosure use an energy source that produces moderate to high pressure in the medicament chamber so that a medicament contained in the medicament chamber is fired at a fast speed and is completely injected into a subject in less than about 10 seconds.
- Other embodiments of the powered injectors are jet injectors, which can be needle-assisted or needle-free jet injectors.
- Jet injector embodiments can be configured to have an energy source selected to produce a high pressure in the medicament chamber to eject the medicament with sufficient pressure, force, and speed to exit the injector as a fluid jet.
- an energy source selected to produce a high pressure in the medicament chamber to eject the medicament with sufficient pressure, force, and speed to exit the injector as a fluid jet.
- the medicament delivered from a jet injector is sprayed rapidly into the tissue, typically remotely from the needle tip, and typically does not deposit the medicament in a bolus local to a needle tip such that leak back is minimized
- Needle-free jet injectors use sufficient pressure and injection speed so that the fluid jet breaks through the outer layer of the skin, depositing the medicament thereunder. Needle-assisted jet injectors can use lower pressures than needle free jet injectors because they employ a needle to break through the outer part of the skin, but have pressures and speeds that are sufficiently high so that the medicament exits the needle tip as a fluid jet.
- the injectors disclosed herein are single-use or -dose injectors, configured to deliver in a single shot the entire volume of the agent(s) contained within a chamber of the injector or within a cartridge contained within the injector.
- the injectors are configured to inject only a portion of the contents of the injector or a cartridge within the injector and can use dosage-setting mechanisms to enable the selection of the volume of injection to be delivered in one shot, or other mechanisms to provide an adjustable dosage.
- the injector can be pre-filled, or configured to receive a cartridge that has the dosage of medicament.
- Alternative embodiments are configured to be fillable as known in the art.
- Injectors provided by the present disclosure may be utilized by patients to self-inject testosterone formulations.
- Various aspects of the present disclosure relate to self-injection of testosterone formulations by a subject without the aid of a health care provider.
- the injectors use a needle to inject testosterone formulations into a target tissue of a subject, such as autoinjector or needle-assisted jet injector embodiments, while other embodiments are needle-free injectors and thus do not require a needle to inject testosterone formulations into a target tissue of a subject.
- the injectors may utilize pressure sufficient to deliver testosterone formulations completely and quickly.
- the injectors may utilize sufficiently high pressure to deliver one or more testosterone formulations completely and quickly in a fluid jet.
- powered injectors provided by the present disclosure do not require any priming or preparatory step in order to place them in condition to deliver an injection, thereby reducing or eliminating exposure of the testosterone formulation to the air and/or premature expulsion of the testosterone formulation from a needle of the injector prior to the delivery shot. Therefore, the risk of contact with the testosterone formulation contained in the injector, by the subject or by a non-user of the injectors, is reduced or eliminated.
- a suitable injector for use with the present invention includes the injector shown in co-pending application Ser. No. 61/763,395 entitled “Needle Assisted Jet Injector Device Having Reduced Trigger Force” and Ser. No. 61/776,283 entitled “Needle Assisted Jet Injector Device Having Reduced Trigger Force”, the contents of each which are hereby incorporated by reference in their entirety.
- an embodiment of an injector according to an embodiment of the present disclosure is presented.
- the embodiment shown in these figures is a needle injector, and depending on the spring used and delivery conduit, including the needle and injection outlet, can be configured as an autoinjector or a needle-assisted jet injector.
- the depicted injector 12 has an outer housing member 14 configured for allowing a user to handle the injector 12 and that substantially houses most of the components shown in FIG. 2 .
- outer housing 14 is formed from two mating portions 14 a , 14 b that can be configured to attach to one another by a snap or press fit or by using adhesives, welding or the like.
- Housing 14 includes a medicament chamber 22 therein that is configured for storing and dispensing one or more liquid medicaments, such as, for example, a testosterone formulation.
- medicament chamber 22 is formed in a prefilled syringe 18 that fits within housing 14 , but other types of fluid chambers can be used, including known types of cartridges that can be prefilled, refillable, or the like with the medicament(s). Additionally, medicament chamber 22 can be integrally formed within housing 14 .
- a stopper portion of a prefilled syringe, or other portion of the prefilled syringe designed to assist in containing the medicament contained within the prefilled syringe is made of a material that is chemically resistant to one or more constituents contained in the prefilled syringe.
- a suitable stopper has minimized or reduced leachable or extractable material and/or is resistant to one or more of acids, bases, hydrocarbons, oils, lipids, carbohydrates, or oxygen.
- suitable stoppers include physically-modified rubber, chemically-modified rubber, teflon, and teflon-coated materials.
- a stopper is comprised of any material that enhances the stability of the stopper and/or its function for the containment of an oil-based composition, and in particular, when compared to the function of a standard rubber stopper used to contain the same oil-based composition.
- a safety member 80 is located on the proximal end of outer housing 14 and is removably affixed thereto by a plurality of tabs that extend through matching openings formed in outer housing 14 to form a press-fit between safety member 80 and outer housing 14 .
- Safety member 80 is configured to prevent or reduce the likelihood of unintended firing of the injection device during, for example, shipping or handling of injector 12 .
- Safety member 80 can be removed by a user of injector 12 to allow for unrestricted use of injector 12 .
- Alternative embodiments of the injectors can be constructed without safety member 80 .
- a sleeve 16 is housed within and mounted to the housing 14 and acts as a syringe support member.
- the sleeve 16 is configured to hold and position a prefilled syringe 18 , carpule or other container of the type known in the art, such as, for example, a BD HypakTM prefilled syringe (Becton, Dickinson and Company).
- a suitable prefilled syringe for use in the depicted embodiments is one which is available in various sizes and volumes, such as the Becton Dickinson HypakTM.
- the glass of the syringe body can be adhered to the needle.
- sleeve 16 is substantially fixed to the housing 12 , such as by snaps, an adhesive, a weld, or another known attachment.
- the prefilled syringe 18 can have a container portion 20 that defines in its interior a medicament chamber 22 , which is prefilled with an injectable medicament such as, for example, a testosterone formulation.
- the medicament container and chamber are provided by other structures, such as a chamber that can be integral with or held in the housing, needle hub 32 , or other injection outlet portion of the injector, for example.
- the length of needle 24 is less than 5 mm. In one embodiment, the length of needle 24 is greater than 5 mm. In one embodiment, the length of needle 24 is less than mm. In one embodiment, the length of needle 24 is greater than 10 mm. In one embodiment, the length of needle 24 is less than 20 mm. In one embodiment, the length of needle 24 is greater than 20 mm.
- the length of needle 24 is about 1 mm, about 2 mm, about 3 mm, about 4, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, or any range determinable from the preceding lengths (for example, about 4 mm to about 6 mm, or about 8 mm to about 10 mm).
- Needle 24 has an injecting tip 26 configured as known in the art to penetrate the tissue of a patient which, in some embodiments, is the skin.
- a needle bore extends through the needle 24 , as known in the art. The bore is in fluid communication with the medicament in the medicament chamber 22 and is open at the needle tip 26 to inject the medicament.
- a plunger 28 that seals the medicament in the medicament chamber 22 .
- a syringe wall comprises a tubular portion which, in some embodiments, is closed at a distal end and open at a proximal end, to define the medicament chamber 22 .
- Plunger 28 is slideably received in the tubular portion.
- the prefilled syringe 18 is configured such that when the plunger 28 is displaced in a distal direction, the volume of the medicament chamber 22 is decreased, forcing the medicament out of the chamber 22 and through the bore of needle 24 .
- a needle hub portion 32 At the distal end of the medicament chamber 22 is a needle hub portion 32 to which the needle is mounted.
- a syringe flange 35 extends radially from the proximal end of the syringe wall.
- the needle can be fluidly connected with the chamber in a different manner, such as by connecting directly to the cartridge, carpule, or other container, or by connecting to another portion of the injector, such as a housing thereof, by a separate needle hub.
- the prefilled syringe 18 has a syringe body 36 wherein the flange 35 , syringe wall, and hub portion 32 is of unitary construction.
- the material comprising the syringe body 36 is glass, but other materials such as, for example, plastic or metal, can be used in other embodiments.
- sleeve 16 has a narrowed bore portion 51 that can be configured to abut the outside of the syringe wall.
- the narrowed bore portion 51 can be made of a resilient material, such as an elastomer, or it can be made unitarily with the rest of sleeve 16 , such as by a series of radially-aligned, resiliently-flexible fingers. Additionally, the proximal portion of the syringe 18 can be held in place by a shock-absorbing device 33 , which, in some embodiments, locates the proximal side of the syringe body 36 axially, and absorbs shocks from the impact of a sudden firing of the ram 60 , such as in jet-injector embodiments, which produce elevated pressures in the medicament chamber 22 or container 20 .
- a shock-absorbing device 33 which, in some embodiments, locates the proximal side of the syringe body 36 axially, and absorbs shocks from the impact of a sudden firing of the ram 60 , such as in jet-injector embodiments, which produce elevated pressures in the medicament chamber 22 or container 20
- a trigger mechanism can also be housed within housing 14 .
- the trigger mechanism includes an inner housing 54 that can be attached to the outer housing 14 , such as by snaps, an adhesive, a weld, or other known attachment.
- Trigger protrusions 56 extend inwardly from the proximal end of the inner housing 54 and are resiliently biased outwardly. Trigger protrusions 56 are received in a recess 58 of ram 60 in blocking association therewith to prevent distal movement of the ram 60 prior to the firing of the device.
- the ram 60 is moved toward the distal end of the injector 10 by an energy source, which in some embodiments is a compression spring 52 , although in other embodiments other suitable energy sources can be used such as elastomer or compressed-gas springs, or a gas generator.
- An example of a compression spring 52 suitable for use with injectors of the present disclosure is a coil spring. Alternative embodiments can also use other suitable trigger mechanisms as known in the art.
- the invention includes a cammed ram assembly as described in U.S. Pat. No. 13,184,229, which is hereby incorporated by reference in its entirety.
- a latch housing 64 can be provided exterior to the inner housing 54 to retain the trigger protrusions 56 in the blocking association in the recess 58 to hold ram 60 in the proximal position until firing is actuated.
- Latch 64 is slideable inside outer housing 14 with respect to the inner housing 54 , in some embodiments in an axial direction, and in some embodiments latch 64 surrounds the inner housing 54 .
- latch 64 is free to move relative to outer housing 14 and is only secured in place, after the removal of safety member 80 , by the pressure exerted thereon by trigger protrusions 56 . In several aspects, nothing is present that biases latch housing 54 away from the proximal end of outer housing 14 , including springs or the like.
- Alternative embodiments can use a medicament container that is shuttled forward when the device is activated to pierce the skin with the needle, and some embodiments use trigger mechanisms that are activated by a button on another part of the injector, such as at the proximal end or on a side of the housing as known in the art.
- the housing 14 can have a needle guard 66 that is moveable with respect to the outer housing 14 .
- the needle guard 66 In the embodiment of the needle guard 66 shown in FIG. 2 , the needle guard 66 is in a protecting position, in which the needle 24 is disposed within the guard 66 .
- a ridge 65 FIG. 8 ) abuts an interior surface of outer housing 14 so as to maintain needle guard 66 within housing 14 when needle guard 66 is fully extended into the protecting position.
- the needle guard 66 can be retractable, in some embodiments into the outer housing 14 , in a proximal direction to an injecting position, in which the needle tip 26 and an end portion of the needle 24 are exposed as shown in FIGS. 6 B and 6 C for insertion into a patient. In some embodiments, the proximal movement of the guard 66 is prevented at the injecting position.
- the needle guard 66 can be associated with the latch 64 such that when the guard 66 is displaced proximally it slides the latch 64 in a proximal direction to release the trigger protrusions 56 from the recess 58 :
- the latch 64 has a latching portion 68 that abuts the inner housing 54 in an association to bias and maintain the trigger protrusions 58 positioned in the blocking association with the ram 60 prior to the firing of the injector 12 .
- the latching portion 68 slides beyond the portion of inner housing 54 that it contacts and the trigger protrusions 56 flex away from the recess 58 of the ram 60 , allowing the trigger protrusions 56 to move radially outwardly from the recess 58 and therefore from the blocking association.
- spring 52 biases the ram 60 against plunger 28 to move distally in the injector 12 .
- a cap 110 can be affixable on the distal end of the injector 12 so as to cover needle guard 66 and prevent accidental displacement thereof during shipping or during handling prior to injection.
- Cap 110 can affix to the distal end of outer housing 14 by press-fit, screw fit or the like.
- cap 110 can include a pair of projections 112 extending inwardly ( FIG. 9 ), that form a distally-facing ridge 114 .
- needle guard 66 can be formed with a pair of radially-extending flanges 67 ( FIG. 8 ) that are configured to abut the distal ridge 114 of projection 112 to secure cap 110 to injector 12 .
- the upper edge 116 FIG.
- cap 110 can abut the distal end of outer housing 14 such that distal ridges 114 of projection 112 are held against flanges 67 .
- This arrangement of the cap 110 prevents compression of the needle guard 66 proximally into the housing, as the cap 110 is juxtaposed between the guard 66 and housing, securing needle guard 66 in the protecting position to help prevent accidental firing of the injection mechanism.
- cap 110 can be removed from injector 12 by twisting cap 110 relative to housing 14 such that projections 112 are moved out of alignment with flanges 67 , which allows the cap 110 to be moved distally away from needle guard 66 .
- the cap 110 engages the housing 14 and/or the needle guard 66 to require an initially elevated force, such as requiring the cap 110 to snap away from its closed position before completing the rotation to remove the cap 110 .
- upper edge 116 of cap 110 can be inclined, as shown in FIG.
- the incline can include a curve, as shown, but generally the edge 116 can have one edge 118 that is higher than the other edge 120 .
- the distal end of outer housing 14 can have a profile that matches that of upper edge 118 of cap 110 . This arrangement requires deflection of cap 110 to allow for twisting thereof and increases the force necessary to cause cap 110 to twist relative to needle guard 66 .
- the cap 110 can have a threaded or cammed association with the flanges 67 , or can have another arrangement therewith so that the cap 110 is removed by rotating.
- Cap 110 can be attached to injector 12 during assembly thereof. This can be done by properly aligning cap 110 and twisting it relative to needle guard 66 while applying a proximally-directed force thereto such that projections 112 move behind flanges 67 .
- flanges 67 can be structured to be deflectable inwardly by disposing them on a corresponding tab 69 formed on needle guard 66 .
- cap 110 can be assembled onto needle guard 66 prior to assembly of spring 72 thereinto, as spring 72 can interfere with the inward deflection of flanges 67 .
- cap 110 can be resiliently deformable to allow cap 110 to be pressed onto needle guard 66 such that projections 112 pass over flanges 67 .
- needle guard 66 can be resiliently biased distally towards the protecting position by compression coil spring 72 .
- the needle guard 66 can have an axial opening 74 to allow the needle 24 pass therethrough, and which may be sized according to the type of injector desired.
- the construction of the injector 12 allows a user to push the distal end of the injector 12 against the patient's skin, pushing the needle 24 into the skin at an insertion location, substantially at the same speed as the injector 12 is pushed into the skin. Once the needle 24 is fully inserted to an insertion point at a desired penetration depth, the trigger mechanism fires causing the injector 12 to inject the medicament into an injection site.
- the needle guard 66 can be configured to allow insertion of the needle 24 to a penetration depth in the skin that is up to about 5 mm below the skin surface.
- the penetration depth is about 0.5 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3.0 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, about 5.5 mm, about 6 mm, about 6.5 mm or any range determinable from the preceding depths (for example, about 0.5 mm to about 2.0 mm or about 3.5 mm to about 5.5 mm).
- the distance by which the needle tip 26 extends past the needle guard 66 or the distal surface of the needle guard 66 that contacts the skin is up to about 5 mm. In some embodiments, the distance by which the needle tip 26 extends past the needle guard 66 or the distal surface of the needle guard 66 that contacts the skin is about 0.5 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3.0 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, about 5.5 mm, about 6 mm or any range determinable from the preceding depths (for example, about 0.5 mm to about 2.0 mm or about 3.5 mm to about 5.5 mm).
- the injector 12 can be configured to allow the needle 24 to be inserted into the patient to a penetration depth in the skin, or alternatively beyond the distal surface of the needle guard 66 , by a distance of up to about 20 mm.
- the injector 12 can be configured to allow the needle 24 to be inserted into the patient to a penetration depth in the skin, or alternatively beyond the distal surface of the needle guard 66 , by a distance of about 0.5 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3.0 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, about 5.5 mm, about 6 mm, about 6.5 mm, about 7.0 mm, about 7.5 mm, about 8.0 mm, about 8.5 mm, about 9.0 mm, about 9.5 mm, about 10.0 mm, about mm, about 11.0 mm, about 11.5 mm, about 12.0 mm, about 12.5 mm, about 13.0 mm, about 13.5 mm, about 14.0 mm, about 14.5 mm, about 15.0 mm, about 15.5 mm, about 16.0 mm, about 16.5 mm, about 17.0 mm, about 17.5
- Other exposed needle 24 lengths can be selected for jet injection to different depths below the skin, with an overall penetration length of between about 0.5 mm and about 20 mm.
- the needle guard 66 can be configured for retracting from a protecting position, in some embodiments covering the entire needle, to an injecting position, in which the desired length of the tip 26 of the needle 24 is exposed.
- the injection device may comprise a collar surrounding the needle and defining a collar cavity, the collar having a peripheral and forward skin-contacting surface that surrounds, is discontinuous, and is radially spaced from the needle and injection site by an area that is sufficiently large to allow a patient's skin to move into the collar cavity to properly position the needle to penetrate the patient for intradermal delivery of the substance to the injection site to allow spread of the injected substance under the skin while inhibiting or preventing backpressure within the skin from forcing the substance out through the injection site.
- An example of such an embodiment can be found in U.S. Pat. No. 8,162,886, hereby incorporated by reference in its entirety.
- Safety member 80 can be removably affixed to the distal end of outer housing 14 and can include a body portion 84 and a pair of resiliently-flexible legs 82 extending therefrom ( FIGS. 4 A and 4 B ).
- Legs 82 are configured to extend into corresponding holes or slots 15 formed in the proximal surface of outer housing 14 and can be shaped to provide a pressure fit within slots 15 to retain safety member 80 on housing 14 .
- the legs 82 can be biased outwardly and can further include tabs 86 disposed on the outside surfaces thereof to engage the inside of outer housing 14 at the location of slots 15 to further the retention of safety member 80 onto outer housing 14 .
- legs 82 are shaped to allow a user to remove safety member from outer housing 14 , when injection is desired. In some embodiments, however, legs 82 prevent safety member 80 from becoming accidentally or unintentionally dislodged from its attachment to outer housing 14 .
- Legs 82 abut ( FIG. 3 ) the proximal-most surface of latching portion 64 when properly attached to outer housing 14 to hinder or prevent jostling or other motion of latching portion 64 in the proximal direction, which would cause the injection mechanism to fire.
- legs 82 are configured in relationship to the housing 14 and the trigger mechanism of the injector 12 such that the force necessary for latching portion 64 to move legs 82 out of slots 15 is sufficient to prevent latching portion 64 from being jostled out of position due to vibration during shipping or from acute shock during shipping or handling caused by dropping of injector 12 .
- Alternative safety members can be used to prevent inadvertent firing of the injector 12 .
- the spring 72 and the prefilled syringe 18 can be configured to jet inject a medicament such as a testosterone formulation.
- the spring 72 applies a force on the plunger 28 that can be sufficient to elevate the pressure within the medicament chamber 22 to a level high enough to eject the medicament from the needle 24 as a fluid jet.
- jet injection is an injection of medicament from the needle tip 26 of the injector 12 with sufficient velocity and force to drive the medicament to locations remote from the needle tip 26 .
- jet injector embodiments whether needle-assisted or needle-free, have an energy source selected to produce a high pressure in the medicament chamber 22 to eject the medicament therefrom with sufficient force and speed to exit the injector 12 as a fluid jet. It is believed that jet injectors deliver medicaments rapidly over a wider surface area under the subject's skin, by essentially “spraying” the medicaments into a subject subcutaneously, thereby rapidly exposing a greater surface area of the subject's target tissue to the medicaments.
- a medicament When delivered by an autoinjector, a medicament typically leaves the autoinjector and is deposited locally, since it is not shot remotely from an injection outlet, and is thus delivered in a bolus typically near the needle tip of the autoinjector.
- an autoinjector requires additional injection time to deliver an injection into resistive media, such as tissue, as opposed to delivery into air.
- embodiments of a powered injector disclosed herein, and in particular embodiments of a disclosed jet injector display approximately no difference in injection time when injecting into resistive media versus air. Because the medicament delivered by a jet injector is essentially sprayed rapidly into the subject's tissue, typically remotely from the needle tip, the medicament does not leave the jet injector as a single drop or bolus and is thus typically not delivered to a subject as a bolus local to a needle tip. Therefore, by using the jet injectors disclosed herein, a medicament can be dispersed into a subject's tissue more efficiently.
- jet injectors deliver medicaments via high pressure and speed
- the delivered medicaments have a far lower tendency to leak back out of the injection site around the needle or injection track. Therefore, leak-back from the depth the medicament is delivered back toward the injection site, and/or back to the surface of the subject's skin, can be significantly reduced by use of a jet injector. Therefore, when used to deliver one or more medicaments according to the present disclosure, such as, for example, a testosterone formulation, jet injectors significantly reduce the risk of exposure to the medicaments outside of the injection site, thereby reducing the risk of exposure to the medicaments to non-users and to the subject himself, in addition to reliably delivering the entire dose to the desired depth.
- Preventing or reducing leak-back is beneficial in improving compliance by ensuring that the medicament remains at the injection site at the desired depth. Preventing or reducing leak-back can also be beneficial to keeping medicaments contained to a single area, thereby preventing inadvertent exposure to the subject and/or to other individuals in his vicinity from leak-back to the surface of the skin. Such exposure can include, for example, direct contact with the medicament on the subject's skin or from atomized medicament that may reach the subject or nearby individuals through the air, or through another medium.
- patients who use the slow injection of a hand-powered hypodermic syringe or autoinjector risk removing the hand-powered injector from the injection site prematurely, before the shot is completed, leading to exposure of the medicament outside the patient's tissue.
- the amount of leak back is less than about 15% of the total injected volume of medicament, and in other embodiments, when used, the amount of leak back is no more than about 0.05% to about 15% of the total injected volume of medicament, about to about 12.5% of the total injected volume of medicament, about 0.2% to about 10% of the total injected volume of medicament, about 0.3% to about 7.5% of the total injected volume of medicament, about 0.4% to about 5% of the total injected volume of medicament, about 0.5% to about 3% of the total injected volume of medicament, about 0.6% to about 2% of the total injected volume of medicament, or about 0.7% to about 1% of the total injected volume of medicament.
- the amount of leak back is less than about 15% of the total weight of the injected medicament. In certain other embodiments, the amount of leak back is no more than about 0.1% to about 15% of the total weight of the injected medicament, about 0.5% to about 12.5% of the total weight of the injected medicament, about 1% to about 10% of the total weight of the injected medicament, about 2% to about 7.5% of the total weight of the injected medicament, or about 3% to about 5% of the total weight of the injected medicament.
- the injector 12 is configured, and the injection conducted, to deliver a medicament in a manner to prevent or significantly reduce leak-back and the risk and incidence of undue exposure of the medicament to the air or to the outside surface of the patient's skin.
- short needles can be used to inject medicaments to different parts of the skin, in some embodiments subcutaneously, without any leak-back.
- a needle 24 that extends about 2.5 mm beyond the distal surface of the needle guard 66 , a 27 gauge needle 24 , and a pressure in the medicament chamber 22 peaking at about 300 p.s.i. and ending at around 100 p.s.i., resulting in a flow rate of about 0.5 mL/sec
- 1 mL of medicament can be successfully be injected without significant leak-back in about 100% of the tested injections as shown, for example, in Table 3 where only slight or measurable, but still slight, wetness at an injection site was observed.
- needle-assisted jet injectors of the present disclosure permit jet injection of one or more medicaments using a very short needle reliably, regardless of the thickness of the patient's skin, age, weight or other factors.
- selection of the type of spring as a power source, adjustment of the force delivered by the spring, and/or the manner in which the spring is packaged within the assembled injector can lead to a significant reduction in the amount of time required to deliver a complete injection into a subject, a significant reduction m the spring force required to deliver the injection, and a longer shelf-life.
- the spring present in many known auto injectors is configured so that a typical injection, in the volume range of about 0.8-1.5 ml, is completely delivered into a subject in 10-15 seconds.
- Embodiments of the injectors of the present disclosure can have their spring configured so as to deliver a complete injection of about about 1.0 ml in volume in about 1 to about 5 seconds, in some embodiments in about 2 to about 4 seconds, and in some embodiments in about 3 seconds. It is believed that this decrease in time will increase patient compliance when embodiments of the autoinjectors of the present disclosure are used, as less time is required to deliver a complete injection and, thus, the patient will experience less pain.
- spring material can be selected so as to only allow a decrease in spring force over the stroke length of the injection as shown.
- Many known autoinjectors show a decrease in spring force over the course of a single injection of less than approximately 20%.
- embodiments of the injectors of the present disclosure can be configured so that their spring force decreases by at least about 25% over the course of a single injection, in some embodiments from about 25% to about 50% over the course of a single injection, in some embodiments from about 30% to about 50% over the course of a single injection, and in some embodiments by about 50% over the course of a single injection
- Spring material can also be selected, and/or the spring can be set in the injector, so as to not have the spring in an overly compressed state during packaging and shipment of the spring to an end user or patient.
- This is advantageous because springs that are overly compressed for expended periods of time become over-stressed and show a loss of force over time
- many known autoinjectors are packaged such that they spend most of their shelf-life with their springs compressed. When packaged in this manner, such known autoinjectors experience a decrease in spring force over time as the autoinjector sits on a shelf awaiting use.
- embodiments of the injectors of the present disclosure can have springs that are made of a material that is sufficiently resilient so as to lose less force over time as it is compressed, and/or can have a spring configured in a fully assembled injector such that it is not in a fully compressed state until the time of injection. In this manner, embodiments of the injectors of the present disclosure lose from about 0% to about 15% of their spring force over a typical shelf life. In some embodiments, the injectors of the present disclosure lose from about 10% to about 12% of their spring force over a three year shelf life.
- injector 12 includes a disabling mechanism, such as a locking element, which can be provided as a locking ring 70 associated with the injection mechanism.
- a disabling mechanism such as a locking element
- locking ring 70 can be disposed between sleeve 16 and needle guard 66 , and can interact with sleeve 16 and needle guard 66 such that the locking ring 70 only permits needle guard 66 to move relative to outer housing 14 through a single injection cycle. This includes movement from the protecting position ( FIG. 6 A ) into the injecting position ( FIGS. 6 B, 6 C ) and then to return to the protecting position ( FIG. 6 D ) under the force of compression spring 72 .
- locking ring 70 moves relative to sleeve 16 from an injecting position to a locking position.
- locking ring 70 is disposed such that the upper arms 71 of locking ring 70 engage a portion of the device that is associated with the medicament chamber 22 , such as, for example, proximal notches 92 formed in the outer surface of sleeve 16 .
- the engagement of upper arms 71 within proximal notches 92 releasably maintains locking ring 70 in the injecting position.
- locking ring 70 can be generally annular in shape so as to surround the medicament chamber 22 , either directly or indirectly, such as by surrounding sleeve 16 .
- Locking ring 70 further includes a pair of lower arms 73 , each having a tab 74 formed on the end thereof.
- tabs 74 are received in slot formed in needle guard 66 such that needle guard 66 is slideable through a predetermined distance over locking ring 70 .
- needle guard 66 slides over locking ring 70 such that tabs 74 reach the end of slot 95 and are depressed inwardly, allowing needle guard 66 to continue to move into the injecting position.
- tabs 74 align with holes 96 of needle guard 66 , allowing lower arms 73 to return to their natural position, wherein the upper surfaces of tabs 74 engage an edge of the holes 96 , thereby coupling locking ring 70 to needle guard 66 .
- upper arms 71 and proximal notches 92 are formed with mating inclined surfaces such that the inclined surfaces of upper arms 71 engage another portion of the injector 12 that is associated with the medicament chamber 22 , such as by extending into proximal notches 92 , but are forced outwardly by distally-directed movement relative thereto.
- This configuration allows the needle guard 66 to cause locking ring 70 to move therewith and out of the injecting position as needle guard 66 moves distally toward the protecting position over sleeve 16 , which remains stationary.
- injector 12 This prevents needle 24 from being accidentally exposed after use of injector 12 .
- Alternative embodiments can use other mechanisms to prevent re-use of the injector or portion thereof. Some embodiments do not employ such a mechanism so that the injector can be reused.
- subsequent injection can be prevented automatically and exposure to or contact with remnants of the medicament that may remain on portions of the injector after the injection, such as on a needle tip or jet injection nozzle, can also be prevented or avoided by the construction of the injector 12 .
- a distal end of an embodiment of a needle-free jet injector is shown.
- the depicted injector can use the systems disclosed herein to fire the injection as described above for the needle injector embodiments, but instead of a needle, a jet nozzle 202 is used to inject the medicament into the subject.
- Nozzle 202 defines a jet outlet 204 having a diameter selected for causing the medicament 200 to exit the nozzle 202 as a fluid jet that is sufficiently strong to pierce the outer skin layers and to continue to the desired depth of injection.
- an injector may have one or more indicators that that injection of medicament has been completed. In an embodiment, an injector may have one or more indicators that injection of medicament is ongoing. In an embodiment, one or more indicators which independently and distinctively indicate that an injection is ongoing and that an injection has been completed. In an embodiment, a first indicator is different than a second indicator.
- Indicators can include, but are not limited to, audible indicators, tactile indicators (e.g., a click or a vibration), visual indicators, physical indicators, electronic indicators, or chemical indicators.
- Table 1 shows the results of a trial comparing medicament leak-back that reached the surface of the skin of a subject after injection; data for needle-assisted jet injectors as compared to hand-driven hypodermic syringes is presented. The total number of injections for each group in the trial was 126, and all were administered by a trained health care professional.
- jet injectors deliver medicaments rapidly, in some embodiments in less than about 2 seconds, the amount of time patients must hold the injector in their tissue is dramatically decreased as compared to an injection delivered by a typical syringe or autoinjector. It is therefore believed that utilizing jet injectors according to the present disclosure will result in increased patient compliance and adherence to instructions and will therefore result in an increase in correctly administered injected doses. Additionally, the speed at which jet injectors deliver medicaments can further enhance patient compliance with regular injections as the amount of pain experienced by a patient self injecting a medicament will be minimized and, in many cases, may not exist.
- a device and method for administering a viscous pharmaceutical formulation to a subject comprises formulating a pharmaceutical formulation in the form of a solution or suspension having a viscosity of between about 25 and 2500 cps, providing the formulation in a injection device that includes a needle having an insertion length of less than about 10 mm or is needle-free; and administering the formulation from the injection device through an orifice having a diameter of at least about 0.2 mm by jet injection into a subject.
- the viscosity referenced herein can be a dynamic viscosity which can be measured by a Brookfied viscometer.
- the viscosity referenced herein can be a kinematic viscosity which is determined by using a capillary viscometer in which a fixed volume of fluid is passed through a small orifice at a controlled temperature under the influence of gravity. In certain embodiments, the viscosity is measured at degrees C. In other embodiments, the viscosity is measured at 25 degrees C.
- an injectable carrier including an amount of testosterone suspended or dissolved therein has a viscosity between 25 and 300 cps at room temperature (e.g., degrees C.). In certain embodiments, the viscosity is between 90 to 120 cps, in other embodiments the viscosity is about 110 cps. In other embodiments the viscosity is greater than or equal to about 70 cps.
- the carrier is coconut oil, soybean oil, sesame oil, castor oil.
- Other oils include: arachis (peanut) oil, castor oil, cottonseed oil, ethyl oleate, polyoxyethylated castor oil (HCO-60, polyoxyl 60 hydrogenated castor oil, Cremophor® EL), safflower oil, and soybean oil
- the formulation includes a pharmaceutically suitable oil and is administered from the injection device at a pressure of greater than about 50 psi.
- the oil is sesame oil.
- the injection device has an injection needle with a bore of about mm or about 0.5 mm.
- Other gauges can also have suitable bores, e.g., 22 gauge, 25 gauge or 27 gauge.
- numeral 132 represents the point in time when an embodiment of injector 12 is fired
- numeral 134 represents the point of completion of injection.
- injection is completed when the plunger 28 hits the distal wall of the medicament container 20 .
- Numeral 136 represents the initial and peak pressure during the injection
- numeral 130 represents the final pressure during the injection.
- the spring 72 has a linear spring constant and an injection-assisting needle 24 is used to puncture the skin before commencing the injection.
- the pressure of injection therefore drops substantially linearly from the start of the injection 132 until the injection is completed 134
- the final pressure 130 at the end 134 of the injection is sufficiently elevated so that even at the end of the firing stroke of ram 60 , the medicament is still jet injected, and a very small amount or none of the medicament is deposited in a bolus around the needle tip 26
- the peak pressure 136 during the injection is less than about 1,000 p.s.i., in some embodiments less than 950 p.s.i., in some embodiments less than 900 p.s.i., in some embodiments less than 850 p.s.i., in some embodiments less than 800 p.s.i., in some embodiments less than 750 p.s.i., in some embodiments less than 700 p.s.i., in some embodiments less than 650 p.s.i., in some embodiments less than 600 p.s.i., in some embodiments less than 550 p.s.i., in some embodiments less than 500 p.s.i., in some embodiments less than 450 p.s.i., in some embodiments less than 400 p.s.i., and in some embodiments less than about 350 p.s.i.
- the pressure 130 applied to the medicament in the medicament chamber 22 can be at least about 80 p.s.i., in some embodiments at least about 90 p.s.i., in some embodiments at least about 100 p.s.i., in some embodiments at least about 150 p.s.i., in some embodiments at least about 200 p.s.i., in some embodiments at least about 250 p.s.i., in some embodiments at least about 300 p.s.i., in some embodiments at least about 350 p.s.i., in some embodiments at least about 400 p.s.i., in some embodiments at least about 450 p.s.i., and in some embodiments at least about 500 p.s.i.
- the initial pressure 136 can be about 330 p.s.i., and the final pressure 130 is about 180 p.s.i. In some embodiments, the initial pressure 136 is about 300 p.s.i., dropping to around 60 p.s.i. at the end 134 of the injection.
- Other injection rates are used for other embodiments discussed herein.
- needle-free jet injectors can exert an injection pressure in the range of about 4,000 p.s.i. or greater.
- Other embodiments of jet injectors utilize lower injection pressures, such as at least about 80 p.s.i. or at least about 60 p.s.i.
- known autoinjectors typically use pressures lower than 60 p.s.i.
- the needles used in some embodiments of both autoinjectors and needle-assisted jet injectors are between 26 and 28 gauge, and in some embodiments are around 27 gauge.
- Other needle gages can also be used where the other components are cooperatively configured to produce the desired injection including, for example, mini-needles.
- the components of the injector 12 can be configured to jet inject one or more medicaments to a subcutaneous injection site.
- injection rates are below about 0.75 mL/sec, in some embodiments below about 0.6 mL/sec, in some embodiments at least about 0.2 mL/sec, in some embodiments at least about 0.3 mL/sec, and in some embodiments at least about 0.4 mL/sec.
- the injection rate is selected from below about 0.75 mL/sec, below about 0.7 mL/sec, below about 0.65 mL/sec, below about 0.6 mL/sec, below about 0.55 mL/sec, below about 0.5 mL/sec, below about 0.45 mL/sec, below about 0.4 mL/sec, below about 0.35 mL/sec, below about 0.3 mL/sec, and below about 0.25 mL/sec.
- the injection rate is about 0.05 mL/sec, 0.1 mL/sec, about 0.15 mL/sec, about 0.20 mL/sec, about 0.25 mL/sec, about 0.30 mL/sec, about 0.35 mL/sec, about 0.40 mL/sec, about mL/sec, about 0.50 mL/sec, about 0.55 mL/sec, about 0.60 mL/sec, about 0.65 mL/sec, about 0.70 mL/sec, about 0.75 mL/sec, about 0.80 mL/sec, about 0.85 mL/sec, about 0.90 mL/sec, or any range determinable from the preceding injection rates (for example, about 0.05 mL/sec to about 1.5 mL/sec or about 0.70 mL/sec to about 0.75 mL/sec).
- injection rates are selected from at least about 0.2 ml/sec, at least about 0.25 ml/sec, at least about 0.3 ml/sec, at least about 0.35 ml/sec, at least about 0.4 ml/sec, at least about 0.45 ml/sec, at least about 0.5 ml/sec, at least about 0.55 ml/sec, at least about 0.6 ml/sec, at least about 0.65 ml/sec, and at least about 0.7 ml/sec.
- the injection of the entire amount of medicament is completed in less than about 15 seconds, in some embodiments in less than about 12 seconds, in some embodiments in less than about 11.5 seconds, in some embodiments in less than about 11.0 seconds, in some embodiments in less than about 10.5 seconds, in some embodiments in less than about 10.0 seconds, in some embodiments in less than about 9.5 seconds, in some embodiments in less than about 9.0 seconds, in some embodiments in less than about 8.5 seconds, in some embodiments in less than about 8.0 seconds, in some embodiments in less than about 7.5 seconds, in some embodiments in less than about 7.0 seconds, in some embodiments in less than about 6.5 seconds, in some embodiments in less than about 6.0 seconds, in some embodiments in less than about 5.5 seconds, in some embodiments in less than about 5.0 seconds, in some embodiments in less than about 4.5 seconds, in some embodiments in less than about 4 seconds, in some embodiments in less than about 3.5 seconds, in some embodiments in less than about 3 seconds, in some embodiments in less than about 3 seconds, in
- the medicament injection takes at least about 1.0 second, about 1.5 seconds, about 2.0 seconds, about 2.5 seconds, about 3.0 seconds, about 3.5 seconds, about 4.0 seconds, about 4.5 seconds, about 5.0 seconds, about 5.5 seconds, about 6.0 seconds, about 6.5 seconds, about 7.0 seconds, about 7.5 seconds, about 8.0 seconds, about 8.5 seconds, about 9.0 seconds, about 9.5 seconds, about 10.0 seconds, about 10.5 seconds, about 11.0 seconds, about 11.5 seconds, about 12.0 seconds, or any range determinable from the preceding times (for example, about 3.0 seconds to about 8 seconds or about 10 seconds to about 12 seconds).
- injection of the medicament occurs at about 0.1 mL/sec, completing an injection of 1 mL in about 10 seconds.
- injector 12 can be configured to deliver a typical flow rate for needle-free jet injection, which can be about 1.5 mL/second, and in some embodiments injector 12 can be configured to deliver a typical flow rate for an autoinjector, which can be about 0.5 mL in 0.3 seconds.
- Injection rates can be affected by a number of factors such as, for example, the gauge of the needle used to inject the medicament, the viscosity of the medicament itself, the glide force of the plunger 28 in the syringe barrel, the temperature of the medicament to be injected, and the temperature of the room in which the injection is administered, as temperature can have a direct effect on viscosity.
- tissue resistance does not impact the rate of injection embodiments of the injectors of the present disclosure are capable of achieving.
- these parameters can be selected and optimized in order to deliver a volume of injection in a desired manner. Such selection and optimization can be readily performed by a person having ordinary skill in the art without undue experimentation.
- an injector may have the capability to heat the testosterone composition contained therein to thereby reduce viscosity and thereby decrease injection time of the composition contained therein.
- a heating device is an integral part of the injector.
- a heating device is external to the injector.
- a heating device has an optional temperature sensing controller.
- an injector has one heating device.
- an injector has more than one heating device.
- Non-limiting examples of heating methods and/or devices include electrical, chemical, and exothermic sources.
- a heating mechanism heats the medicament contained within the injector to a temperature above room temperature.
- a heating device heats the medicament contained within the injector to a temperature about 5 degrees C. above room temperature, or about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, or about 50 degrees C. above room temperature (e.g., 20 to 25 degree C.).
- the heating mechanism is an electronic, chemical or mechanical heating mechanism.
- the mechanism or method of use includes placing a device proximal to a heat source (e.g., under a human arm).
- a heating device or mechanism further comprises at least one indicia that the heating device is operational, non-operational, and/or at the desired temperature.
- a heating device has one or more indicia to indicate to the user that the device has reached a temperature suitable for dispensation of the medicament from the device.
- an indicator is a visual indicator.
- an indicator is an audible or a tactile indicator
- a viscous medicament that would otherwise require a longer injection time can still be injected into a subject in the rates set forth above by varying the gauge of the needle.
- a 26 gauge needle can be utilized with the needle-assisted injectors of the present disclosure to inject a viscous material
- a 27 gauge needle can be utilized with the needle-assisted injectors of the present disclosure to inject a viscous material
- a 28 gauge needle can be utilized with the needle-assisted injectors of the present disclosure to inject a viscous material.
- the rates of injection are the same as those rates disclosed above.
- a 27 gauge needle can be utilized with one or more embodiments of the injectors of the present disclosure to deliver 1.0 ml of an aqueous solution into air in a duration of time from between about 1.0 to about 2.0 seconds, in some embodiments between about 1.5 and about 2.0 seconds, and in some embodiments in about 1.7 seconds.
- a 27 gauge needle can be utilized with one or more embodiments of the injectors of the present disclosure to deliver 1.0 ml of an aqueous solution into tissue in a duration of time from between about 1.0 to about 2.0 seconds, in some embodiments between about 1.3 and about 2.0 seconds, in some embodiments in about 1.5 seconds, and in some embodiments in about 1.3 seconds.
- a 27 gauge needle can be utilized with one or more embodiments of the injectors of the present disclosure to deliver 1.0 ml of a viscous solution, having a viscosity equivalent to 10% w/w polyethylene glycol 20,000 in water, into air in a duration of time from between about 1.0 to about 5.0 seconds, in some embodiments between about 2.5 and about 5.0 seconds, in some embodiments in about 4.3 seconds, and in some embodiments in about 4.0 seconds.
- a 27 gauge needle can be utilized with one or more embodiments of the injectors of the present disclosure to deliver 1.0 ml of a viscous solution, having a viscosity equivalent to 20% w/w polyethylene glycol 20,000 in water, into air in a duration of time from between about to about 15 seconds, in some embodiments between about 12 and about 15 seconds, and in some embodiments in about 14 seconds.
- injectors of the present disclosure can be configured to produce a flow rate, or a rate of injection, of 0.5 ml/second for aqueous solutions having a cP of, or close to, 1.0, through a 27 gauge needle.
- injectors of the present disclosure can be configured to produce a flow rate, or a rate of injection, into skin of 0.5 ml/second for aqueous solutions having a cP of, or close to, 1.0, through a 27 gauge needle.
- U.S. Pat. No. 6,391,003 discloses the experimental results of pressures that can be successfully applied to a medicament in a glass cartridge, using 26 and 27 gauge needles.
- Table 2 illustrates exemplary injections with different peak pressures that can be used with a needle-assisted jet injector, especially when using a glass, prefilled syringe:
- needle-free injectors may use higher pressures to penetrate the skin without a needle, and autoinjectors will typically use lower pressures to simulate a hand-powered syringe injection.
- the present disclosure relates to an auto-injector for dispensing a predetermined dosage of a medicament comprising testosterone (e.g., preservative-free), the auto-injector including a housing that is preferably oval or elliptical in shape such that it is more ergonomic.
- a housing that is preferably oval or elliptical in shape such that it is more ergonomic.
- U.S. Pat. Nos. 7,449,012 and 7,794,432 are hereby incorporated by reference in their entirety.
- the oval shape prevents the auto-injector from rolling off a table or flat surface, while providing a larger surface area for printing user instructions.
- a cartridge container is disposed within the housing.
- a cartridge is received within the cartridge container.
- the cartridge has at least one opening therein and contains a medicament.
- the medicament is rearwardly confined by a plunger.
- the cartridge includes a needle assembly to dispense the medicament therethrough.
- the cartridge is advanced within the cartridge container from a stored position to an operation position where the needle extends from the cartridge container such that the dose of medicament can be administered.
- An actuation assembly or power pack provides a stored energy source that is capable of being released to drive the plunger within the cartridge to dispense the medicament through the needle assembly into the user and allowing the needle to be accessible on activation.
- Another aspect of the auto-injector of an alternative embodiment is the provision of a needle cover received within the housing.
- the needle cover shields the user from inadvertent exposure to the needle after use of the auto-injector providing sharps protection.
- the operation of the needle cover is fail safe because the cover will not deploy until after the needle penetrates the user.
- the needle of the cartridge extends through an opening in the needle cover to permit the dispensing of a dose of medicament.
- the needle cover is held in a locked position to prevent the cover from being retracted to expose the needle.
- the needle cover has a locked retracted position prior to activation of the auto-injector, thus maintaining a compact configuration of the device prior to use.
- the actuation forces associated with the auto-injector are not imparted on the needle cover.
- the auto-injector has a first locking assembly that holds the needle cover in the first locked position.
- the first locking assembly may be located on the cartridge container.
- the first locking assembly may include at least one locking tooth pivotally connected to the cartridge container or the needle cover.
- Each locking tooth releasably engages the needle cover and includes a locking surface constructed and arranged to contact a surface on the needle cover or the cartridge container.
- Each locking tooth may be formed as a separate component that is connected to the container or cover. It is contemplated that the locking teeth may be formed as integral parts of the needle cover or cartridge.
- a spring force of the locking tooth biases the locking surface into contact with the needle cover. The spring force may be provided by a spring portion of the locking tooth.
- the spring force may also be provided by a separate spring assembly biasing the locking surface into contact with the needle cover.
- Each locking tooth is preferably pivotally connected to the cartridge container. Each locking tooth pivots in response to movement of the cartridge within the cartridge container. It is also contemplated that the locking teeth can pivot in response to movement of the collet or the power pack. Typically, the locking surface pivots out of contact with the needle cover when the locking tooth pivots in response to the movement of the cartridge.
- the spring force and the force exerted by the locking teeth on the cartridge are controlled such that they negligibly or minimally impede the motion of the cartridge during the injection operation to avoid any premature rupturing of the diaphragm within the cartridge and premature administering of the medicament.
- the needle cover is spring biased so that the cover is biased outwardly from the housing to cover the exposed needle after the first locking assembly is released.
- the auto-injector has a second locking assembly that holds the needle cover in the second locked position.
- the second locking assembly may be located on the cartridge container, the outer body or the cover member.
- the second locking assembly may include at least one locking arm or wing preferably connected to the cartridge container. Each locking arm is spaced from the cartridge container such that the locking arm can be temporarily compressed against the cartridge container as the needle cover moves from the first locked position to the second locked position.
- Each locking arm has a locking surface to engage the needle cover when the needle cover is in the locked extended position.
- Each locking arm has a thick strut portion and a thin strut portion, wherein the thick strut portion is outwardly curved and the thin strut portion is inwardly curved.
- This construction maintains the locking arm in a normal uncompressed state to reduce stress on the cartridge container. This also penults a smooth deployment of the cover member. Furthermore, this arrangement ensures that the thick strut portion will buckle into a stable condition. This creates a stronger lock to prevent the cover member from being moved rearwardly to a retracted position.
- the inwardly curved nature of the thin strut portion allows the thick portion to buckle in a controlled manner to a stable condition.
- the outwardly curved shape of the thick strut portion provides for fail safe locking of the cover member in the extended position. In the event that the thin strut breaks, the thick strut portion will still engage the cover member to maintain it in an extended locked position.
- the cartridge container of an alternative embodiment may further include at least one ledge extending outwardly therefrom.
- Each ledge is constructed and arranged to engage an edge of an opening in the needle cover to limit the travel of the needle cover with the respect to the cartridge container when the needle cover is in the extended position.
- the second locking assembly limits the inward travel of the needle cover.
- the needle cover and the cartridge container contain openings formed therein. When the openings are aligned prior to activation of the auto-injector, user can view the contents of the cartridge through the housing and the openings.
- the housing may be transparent or opaque.
- the housing When opaque, the housing may contain an opening that can be aligned with the openings in the needle cover and cartridge container so that the color of the medicament may be checked to determine whether or not the medicament is suitable for injection. If the medicament is discolored, the user will know not to administer the medicament.
- the openings are not aligned after operation of the auto-injector, the user is no longer able to view the contents of the cartridge through the openings providing a visual indication to the user that the auto-injector has been used.
- Another aspect of an alternative embodiment is the construction and arrangement of the actuation assembly or power pack, which is mounted within the housing adjacent to an open end.
- a release pin or safe pin is removably attached to the actuation assembly to prevent inadvertent actuation of the auto-injector when the release pin is in place.
- a pin or stem on the release pin is received within an opening in the actuation assembly to prevent actuation of the auto-injector.
- This opening in the power pack is spaced from the open end of the housing such that the opening is less visible to a user prior to administering the drug. This arrangement is provided so that user will not orient the incorrect end of the auto-injector against the injection surface of the user.
- the power pack is recessed or spaced from the end of the housing, which provides an indication to the user that pressing the power pack will not operate the auto-injector.
- the recessed nature of the power pack serves to hide the release pin hole in the power pack when the user is viewing the instructions on the outer body such that the user does not confuse the release pin hole with the opening through which the needle passes for administering the medicament.
- the release pin includes at least one tab extending therefrom. The tab is compression fit into a complimentary recess formed in the actuation assembly to prevent the inadvertent removal of the release pin. The tabs also prevent rotation of the release pin such that the user easily recognizes that the release pin must be pulled in order to be removed.
- the actuation assembly of an alternative embodiment includes an outer body, which is configured to engage the release pin.
- the outer body is constructed to be connected to the housing.
- An inner body is operatively coupled to the outer body.
- At least one retention tab on the inner body secures the inner body to the outer body.
- the inner body is capable of limited movement with respect to the outer body.
- a collet is operatively coupled to the inner body.
- An energy source is operatively connected to the inner body and the collet.
- the collet in the present invention is molded as a single piece. No spacers or other components are provided between the collet and the plunger in the cartridge. This arrangement simplifies construction of an alternative embodiment. Different sized collets can be produced and installed into the actuation assembly, such that only the collet needs to altered when different sized cartridges are used or a different sized dosage of medicament is to be administered.
- a medicament of the present invention can be any drug, including testosterone, which can be useful alone or in combination with other embodiments and/or devices encompassed herein.
- the drug is testosterone.
- a testosterone formulation encompassed herein comprises at least one preservative, and in particular, a pharmaceutically-acceptable preservative, and more particularly, a preservative suitable for one or more of intramuscular, subdermal, and subcutaneous administration.
- Suitable preservatives include, but are not limited to, antimicrobial agents, halogenated alcohols, parabens, and phenylmercuric salts.
- Non-limiting examples of preservatives include phenol, meta-cresol, benzyl alcohol, methyl paraben, propyl paraben, butyl paraben, benzalkonium chloride, chlorobutanol, thimerosal, phenylmercuric acetate, phenylmercuric borate, and phenylmercuric nitrate.
- a testosterone formulation encompassed herein does not comprise a preservative or is free of a preservative and in particular, free of a preservative described above.
- a preservative-free testosterone formulation encompassed herein comprises testosterone enanthate.
- a preservative free testosterone formulation is a unit dose of testosterone or a pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier.
- a preservative free testosterone formulation is a multiple of at least two unit doses of testosterone or a pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier.
- the composition is free or substantially free of precipitate (e.g., testosterone enanthate or testosterone cypionate precipitate).
- a testosterone formulation (e.g., preservative-free) comprises at least one viscous carrier.
- a testosterone formulation (e.g., preservative-free) includes testosterone in oil.
- a testosterone formulation (e.g., preservative-free) includes testosterone in sesame oil.
- testosterone in a composition encompassed herein is present in an amount selected from: about 5 mg, about 10 mg, about 15, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about 210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, about 245 mg, about 250 mg, about 255 mg, about 260 mg, about 265 mg
- the amounts of testosterone encompassed herein may be contained within a suitable volume of fluid (e.g., a suitable carrier or oil), based on the method of administration and/or the device used for administration, desired testosterone concentration, etc., among other things.
- a suitable volume of fluid e.g., a suitable carrier or oil
- the amount of medicament contained in and injected from medicament chamber 22 can be between about 0.02 mL and about 4 mL, in some embodiments less than about 3 mL.
- the amount of medicament contained in and injected from medicament chamber 22 can be about 0.02 mL, about 0.04 mL, about 0.06 mL, about 0.08 mL, about 1.00 mL, about 1.02 mL, about 1.04 mL, about 1.06 mL, about 1.08 mL, about 2.00 mL, about 2.02 mL, about 2.04 mL, about 2.06 mL, about 2.08 mL, about 3.00 mL, about 3.02 mL, about 3.04 mL, about 3.06 mL, about 3.08 mL, about 4.00 mL, about 4.02 mL, about 4.04 mL, about 4.06 mL, about 4.08 mL, about 5.00 mL, or any range determinable from the preceding volumes (for example, about 0.04 mL to about 5.00 mL or about 1.04 mL to about 3.02 mL).
- a pre-filled syringe 18 containing the desired amount of medicament is assembled into the remaining parts of an injector 12 .
- the pre-filled syringe 18 contains from about 0.02 mL to about 4.00 mL of medicament-containing fluid.
- the pre-filled syringe 18 contains about 0.02 mL, about 0.04 mL, about 0.06 mL, about 0.08 mL, about 1.00 mL, about 1.02 mL, about 1.04 mL, about 1.06 mL, about 1.08 mL, about 2.00 mL, about 2.02 mL, about 2.04 mL, about 2.06 mL, about 2.08 mL, about 3.00 mL, about 3.02 mL, about 3.04 mL, about 3.06 mL, about 3.08 mL, about 4.00 mL, about 4.02 mL, about 4.04 mL, about 4.06 mL, about 4.08 mL, about 5.00 mL, or any range determinable from the preceding volumes (for example, about 0.04 mL to about 5.00 mL or about 1.04 mL to about 3.02 mL) of one or more medicaments.
- an ester form of testosterone is used.
- a testosterone formulation encompassed herein comprises testosterone enanthate and/or testosterone cypionate, collectively referred to herein as “testosterone”. It is understood that alternative compounds that include the testosterone moiety are within the scope of the term “testosterone”, including active metabolites of testosterone.
- a testosterone formulation encompassed herein is such that it can be administered through a fine-gauge needle, the methods of administration and the devices for administration encompassed and/or described in detail elsewhere herein.
- a non-limiting example of a fine gauge needle is a 27 gauge needle.
- other examples of fine gauge needles are described in detail elsewhere herein.
- a testosterone formulation encompassed herein, when administered in combination with device encompassed herein, a dose can be administered using a force sufficient to smoothly overcome resistance to flow through the syringe body or needle. Methods of determining and optimizing flow rate for injection of a medicament are also described in detail elsewhere herein.
- the present disclosure provides, in part, a method, device, and composition for treating hypogonadism, reduced infertility, lack of libido or erectile dysfunction, osteoporosis and anemia, a method for encouraging penile enlargement and height growth, and method of stimulating bone marrow and appetite.
- the concentration of testosterone in the blood stream of a subject will depend on the amount of testosterone in the composition administered to the subject as well as the route of administration and the specific formulation used.
- a subject is treated with a single dose of a composition as encompassed herein. In an embodiment, a subject is treated with two or more doses of a composition as encompassed herein. In an embodiment, a subject is treated with multiple doses of a composition as encompassed herein. In an embodiment, a subject treated with multiple doses is treated for at least one day. In an embodiment, a subject treated with multiple doses is treated for at least one week. In an embodiment, a subject treated with multiple doses is treated for at least one month. In some embodiments, a patient is injected weekly or bi-weekly with one or more testosterone doses. The patient is preferably, but not limited to, being injected in the abdomen or thigh.
- a composition comprising testosterone e.g., a preservative-free testosterone composition administered to a subject as encompassed herein provides pharmacokinetics, including systemic bioavailability, that has substantially the same (or similar) pharmacokinetics, including systemic bioavailability, of testosterone when the same dose of testosterone is administered to said subject using needle and syringe, intramuscularly or subcutaneously.
- the method of treating hypogonadism as encompassed herein comprises introducing into the subcutaneous, intradermal, or intramuscular tissue of a subject, from a needle assisted jet injection device, a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein the pharmacokinetic profile of said testosterone delivered by said needle assisted jet injection device is substantially the same as the pharmacokinetic profile of the same dose of said testosterone when administered to said subject via needle and syringe, intramuscularly or subcutaneously.
- a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg
- the values obtained or calculated for measured testosterone can be in reference to total testosterone, free testosterone, bio-available testosterone or serum testosterone.
- testosterone administered in accordance with the disclosure encompassed herein achieves comparable, e.g., bioequivalence, pharmacokinetic profile by generating C max and T max for the same period of time as compared to when the same dose of testosterone is delivered via a needle and syringe, intramuscularly, intradermally, or subcutaneously.
- testosterone administered in accordance with the disclosure encompassed herein achieves a pharmacokinetic profile that is superior to that obtained by generating C max and T max for the same period of time as compared to when the same dose of testosterone is delivered via a needle and syringe, intramuscularly, intradermally, or subcutaneously.
- a composition comprising testosterone (e.g., a preservative-free composition) administered to a subject in accordance with the methods disclosed herein provides enhanced pharmacokinetics, including systemic bioavailability, of testosterone when the same dose of testosterone is administered to said subject using one of a transdermal cream, gel or patch or needle and syringe, intramuscularly, intradermally, or subcutaneously.
- testosterone e.g., a preservative-free composition
- a composition comprising testosterone (e.g., a preservative-free composition) administered to a subject in accordance with the methods disclosed herein provides enhanced pharmacokinetics, including systemic bioavailability, of testosterone when the same dose of testosterone is administered to said subject using one of a transdermal cream, gel or patch or needle and syringe, intramuscularly, intradermally, or subcutaneously.
- a method of administering testosterone in accordance with the disclosure encompassed herein comprises introducing into the subcutaneous, intradermal, or intramuscular tissue of a subject, from an injector device as encompassed herein and described elsewhere herein, a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein the pharmacokinetic profile of testosterone delivered by the injector device is enhanced relative to the pharmacokinetic profile of the same dose of said testosterone when administered to said subject via one of a transdermal cream, gel or patch or needle and syringe, intramuscularly, intradermally, or subcutaneously.
- a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein the pharmacokinetic profile of testosterone delivered by the injector device is enhanced relative to the pharmacokinetic profile of the same dose of said testosterone when administered to said subject via one of a transdermal cream, gel or patch or needle and
- a method of administering testosterone in accordance with the disclosure encompassed herein comprises introducing into the subcutaneous, intradermal, or intramuscular tissue of a subject, from a needle assisted jet injection device as encompassed herein and described elsewhere herein, a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein the pharmacokinetic profile of testosterone delivered by the needle assisted jet injection device is bioequivalent to the reference-listed drug when administered via needle and syringe, intramuscularly, intradermally, or subcutaneously.
- bioequivalent pharmacokinetic profile of testosterone delivered by the needle assisted jet injection device is enhanced as compared to the reference-listed drug when administered via needle and syringe, intramuscularly, intradermally, or subcutaneously.
- the pharmacokinetic profile provides a linear increase in testosterone exposure with increases in dose of testosterone administered.
- the pharmacokinetic profile provides dose proportional increases in testosterone exposure (AUC and/or C max )
- the pharmacokinetic profile provides a linear or nonlinear relationship between AUC (ng*h/ml) of testosterone and dose of testosterone when the AUC (ng*h/ml) values are plotted against the corresponding dose values in a Cartesian Plane.
- the pharmacokinetic profile provides a linear or nonlinear relationship between C max of testosterone and dose of testosterone when the C max values are plotted against the corresponding dose values in a Cartesian Plane.
- Pharmacokinetic information concerning testosterone and a needle assisted jet injector can also be found in co-pending provisional application Ser. No. 61/621,298, the content of which is hereby incorporated by reference in its entirety.
- one embodiment of the present invention provides a method of treating hypogonadism in a subject in need of treatment, said method comprising introducing into the subcutaneous or intramuscular tissue of a patient in need of testosterone, from a needle assisted jet injection device, a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein said method provides a pharmacokinetic profile whereby testosterone exposure increases linearly in proportion to increases in the dose strength (or level) of testosterone.
- the pharmacokinetic profile provides an AUC that increases linearly in proportion to increases in the dose strength (or level) of testosterone administered.
- the pharmacokinetic profile provides a C max that increases linearly in proportion to increases in testosterone dose level administered.
- a method of administering testosterone comprises administering a composition comprising a unit dose of testosterone (e.g., preservative-free) or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained at a therapeutically effective level for a period of time.
- a Z1 time period is the time period for which the plasma level of testosterone is maintained at a therapeutically effective level.
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at a therapeutically effective level starting at about 1 minute after administration and ending at about 1 month after administration.
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at a therapeutically effective level starting at about 2 minutes after administration, or at about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours about 7 hours about 8 hours about 9 hours, about 10 hours, about 11 hours, or about 12 hours after administration, up to about 1 month after administration.
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at a therapeutically effective level starting at about 1 minute after administration and ending at about 25 days after administration, about 20 days after administration, about 15 days after administration, about 14 days after administration, about 13 days after administration, about 12 days after administration, about 11 days after administration, about 10 days after administration, about 9 days after administration, about 8 days after administration, about 7 days after administration, about 6 days after administration, about 5 days after administration, about 4 days after administration, about 3 days after administration, about 2 days after administration, about 1 day after administration, or about 0.5 days after administration.
- a first dose has a first profile and subsequent doses (which may be the same as or different from the first dose) impart different profiles.
- the pharmacokinetic profile of a patient can be customized to meet a particular patient's needs through the use of the present invention.
- the present invention can be used to maintain therapeutic levels of testosterone during and/or across a prescribed dosing cycle (e.g., once weekly dosing for: 2 weeks, 3 weeks, 4 weeks, 5 weeks, two months, five months, a year, or more).
- a method of administering testosterone comprises administering a composition comprising a unit dose of a testosterone (e.g., preservative-free) or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration, the plasma level of testosterone is maintained between about 300 ng/dl and about 1100 ng/dl for a time period, “Z1”
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone between, e.g., about 300 ng/dl and about 1100 ng/dl starting at about 1 minute after administration and ending at about 1 month after administration.
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone between, e.g., about 300 ng/dl and about 1100 ng/dl starting at about 2 minutes after administration, or at about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours about 7 hours about 8 hours about 9 hours, about 10 hours, about 11 hours, or starting at about 12 hours after administration, up to about 1 month after administration.
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone between, e.g., about 300 ng/dl and about 1100 ng/dl starting at about 1 minute after administration and ending at about 25 days after administration, about 20 days after administration, about 15 days after administration, about 14 days after administration, about 13 days after administration, about 12 days after administration, about 11 days after administration, about 10 days after administration, about 9 days after administration, about 8 days after administration, about 7 days after administration, about 6 days after administration, about 5 days after administration, about 4 days after administration, about 3 days after administration, about 2 days after administration, about 1 day after administration, or ending about 0.5 days after administration.
- about 300 ng/dl and about 1100 ng/dl starting at about 1 minute after administration and ending at about 25 days after administration, about 20 days after administration, about 15 days after administration, about 14 days after administration, about 13 days after administration, about 12 days after administration, about 11 days after administration, about 10 days after administration, about 9 days
- the plasma level of testosterone is maintained at a value selected from the group consisting of about 300 ng/dl to about 1100 ng/dl, about 350 ng/dl to about 1050 ng/dl, about 400 ng/dl to about 1000 ng/dl, about 450 ng/dl to about 950 ng/dl, about 500 ng/dl to about 900 ng/dl, about 550 ng/dl to about 850 ng/dl, about 600 ng/dl to about 800 ng/dl, about 650 ng/dl to about 750 ng/dl, and about 675 ng/dl to about 725 ng/dl.
- the plasma level of testosterone is maintained at a value selected from the group consisting of about 300 ng/dl, about 350 ng/dl, about 400 ng/dl, about 450 ng/dl, about 500 ng/dl, about 550 ng/dl, about 600 ng/dl, about 650 ng/dl, about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, and about 1100 ng/dl.
- the plasma level of testosterone is maintained at a value selected from the group consisting of at least about 300 ng/dl, at least about 350 ng/dl, at least about 400 ng/dl, at least about 450 ng/dl, at least about 500 ng/dl, at least about 550 ng/dl, at least about 600 ng/dl, at least about 650 ng/dl, at least about 700 ng/dl, at least about 750 ng/dl, at least about 800 ng/dl, at least about 850 ng/dl, at least about 900 ng/dl, at least about 950 ng/dl, at least about 1000 ng/dl, at least about 1050 ng/dl, and at least about 1100 ng/dl.
- the plasma level of testosterone is maintained at a value selected from the group consisting of about 300 ng/dl or less, about 350 ng/dl or less, about 400 ng/dl or less, about 450 ng/dl or less, about 500 ng/dl or less, about 550 ng/dl or less, about 600 ng/dl or less, about 650 ng/dl or less, about 700 ng/dl or less, about 750 ng/dl or less, about 800 ng/dl or less, about 850 ng/dl or less, about 900 ng/dl or less, about 950 ng/dl or less, about 1000 ng/dl or less, about 1050 ng/dl or less, and about 1100 ng/dl or less.
- the level of testosterone is maintained as illustrated in FIG. 12 .
- the level of testosterone maintained as illustrated in FIG. 12 is in a mammal.
- the level of testosterone maintained as illustrated in FIG. 12 is in the serum of a mammal.
- the mammal is a human.
- a method for maintaining elevated plasma levels of testosterone in a mammal in need thereof.
- this entails maintaining plasma levels from a subcutaneous dose at or above therapeutic levels (e.g., about 400 ng/dl, about 500 ng/dl, about 600 ng/dl, about 700 ng/dl, about 800 ng./ml, about 900 ng/dl) for an extended period of time.
- the level is maintained for a period of time that is longer than an intramuscular dose of the same volume and concentration.
- the method comprises administering a composition comprising a unit dose of testosterone (e.g., preservative-free) or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained at an elevated level of up to about 1800 ng/dl for a period of time.
- a composition comprising a unit dose of testosterone (e.g., preservative-free) or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained at an elevated level of up to about 1800 ng/dl for a period of time.
- the time period for which plasma levels of testosterone are maintained at an elevated level is referred to as a “Z2 time period”.
- the plasma level of testosterone is maintained at an elevated value selected from the group consisting of about 300 ng/dl to about 1800 ng/dl, about 400 ng/dl to about 1800 ng/dl, about 500 ng/dl to about 1800 ng/dl, about 600 ng/dl to about 1800 ng/dl, about 700 ng/dl to about 1800 ng/dl, about 800 ng/dl to about 1800 ng/dl, about 900 ng/dl to about 1800 ng/dl, about 1000 ng/dl to about 1800 ng/dl, about 300 ng/dl to about 1100 ng/dl, about 400 ng/dl to about 1100 ng/dl, about 500 ng/dl to about 1100 ng/dl, about 600 ng/dl to about 1100 ng/dl, about 700 ng/dl to about 1100 ng/dl, about 800 ng/dl to about 1100 ng/dl, about
- the blood plasma levels of testosterone are maintained primarily between 400 and 1100 ng/dl, more typically between 400 and 900 ng/dl, during the course of a treatment regimen.
- blood plasma levels at a value between about 400 and about 1000 ng/dl is considered “therapeutically effective,” particularly for steady state maintenance of testosterone levels during a treatment regimen.
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at an elevated level starting at about 1 minute after administration and ending at about 1 month after administration.
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at an elevated level starting at about 2 minutes after administration, or at about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 2 hours, about 3 hours, about 4 hours, about hours, about 6 hours about 7 hours about 8 hours about 9 hours, about 10 hours, about 11 hours, or about 12 hours after administration, up to about 1 month after administration.
- a composition encompassed herein when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at an elevated level starting at about 1 minute after administration and ending at about 25 days after administration, about 20 days after administration, about 15 days after administration, about 14 days after administration, about 13 days after administration, about 12 days after administration, about 11 days after administration, about 10 days after administration, about 9 days after administration, about 8 days after administration, about 7 days after administration, about 6 days after administration, about 5 days after administration, about 4 days after administration, about 3 days after administration, about 2 days after administration, about 1 day after administration, or about 0.5 days after administration.
- a method for obtaining a peak plasma levels of testosterone in a mammal in need thereof.
- a method is provided herein, using the compositions and devices encompassed herein, to obtain a peak plasma concentration of testosterone, after which the plasma concentration of testosterone decreases to a therapeutically effective level for a period of time.
- a method is provided herein, using the compositions and devices encompassed herein, to obtain a peak plasma concentration of testosterone, after which the plasma concentration of testosterone decreases to an elevated level for a period of time.
- a peak level of testosterone is in the range of about 400 ng/dl to 2400 ng/dl, 500 ng/dl to 2400 ng/dl, 600 ng/dl to 2400 ng/dl, 700 ng/dl to 2400 ng/dl, 800 ng/dl to 2400 ng/dl, 900 ng/dl to 2400 ng/dl, 1000 ng/dl to 2400 ng/dl, 1100 ng/dl to 2400 ng/dl, 1200 ng/dl to 2400 ng/dl, 1300 ng/dl to 2400 ng/dl, 1400 ng/dl to 2400 ng/dl, 1500 ng/dl to 2400 ng/dl, 1600 ng/dl to 2400 ng/dl, 1700 ng/dl to 2400 ng/dl, 1800 ng/dl to 2400 ng/dl, 1900 ng/dl to
- a method is provided herein, using the compositions and devices encompassed herein, to obtain a peak plasma concentration of testosterone, after which the plasma concentration of testosterone decreases to lower-than-peak level for a period of time, the lower-than-peak level selected from about 300 ng/dl to about 1800 ng/dl, about 400 ng/dl to about 1800 ng/dl, about 500 ng/dl to about 1800 ng/dl, about 600 ng/dl to about 1800 ng/dl, about 700 ng/dl to about 1800 ng/dl, about 800 ng/dl to about 1800 ng/dl, about 900 ng/dl to about 1800 ng/dl, about 1000 ng/dl to about 1800 ng/dl, about 300 ng/dl to about 1100 ng/dl, about 400 ng/dl to about 1100 ng/dl, about 500 ng/dl to about 1100 ng/dl, about 600 ng/dl to about
- a method is provided herein, using the compositions and devices encompassed herein, to obtain a peak plasma concentration of testosterone, in which the peak plasma concentration of testosterone is achieved in about 48 hours, about 36 hours, about 24 hours, about 18 hours, about 12 hours, about 11 hours, about 10 hours, about 9 hours, about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours about 2 hours, about 1 hours, or about 0.5 hours.
- the peak plasma concentration of testosterone is achieved in less than 48 hours, less than 36 hours, less than 24 hours, less than 18 hours, less than 12 hours, less than 11 hours, less than 10 hours, less than 9 hours, less than 8 hours, less than 7 hours, less than 6 hours, less than 5 hours, less than 4 hours, less than 3 hours less than 2 hours, less than 1 hours, or less than 0.5 hours.
- a testosterone composition as encompassed herein provides a plasma level of testosterone that is maintained at a therapeutically-effective level for a longer period of time than an equivalent dose of testosterone when administered to the same subject via one of a transdermal cream, gel or patch or needle and syringe, intramuscularly, intradermally, or subcutaneously.
- a testosterone composition as encompassed herein e.g., preservative-free maintains a higher plasma concentration of testosterone than would a equivalent testosterone administered to the same subject via one of a transdermal cream, gel or patch or intramuscular injection by needle and syringe over the same time period.
- a method of administering testosterone comprises administering a composition comprising a unit dose of testosterone in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained between about 700 ng/dl and about 1800 ng/dl for a time period, “Z2”, wherein the plasma level of testosterone is also maintained between about 300 ng/dl and about 1100 ng/dl for a time period, “Z3”, which is the time after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration.
- the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at about 1 day post-administration, at about 2 days post-administration, at about 3 days post-administration, at about 4 days post-administration, at about 5 days post-administration, at about 6 days post-administration, at about 7 days post-administration, at about 8 days post-administration, at about 9 days post-administration, at about 10 days post-administration, at about 11 days post-administration, at about 12 days post-administration, at about 13 days post-administration, or at about 14 days post-administration.
- the plasma level of testosterone is maintained, for a Z2 time period, at or between a level selected from: about 700 ng/dl and about 1800 ng/dl, about 750 ng/dl and about 1750 ng/dl, about 800 ng/dl and about 1700 ng/dl, about 850 ng/dl and about 1650 ng/dl, about 900 ng/dl and about 1600 ng/dl, about 950 ng/dl and about 1550 ng/dl, about 1000 ng/dl and about 1500 ng/dl, about 1050 ng/dl and about 1450 ng/dl, about 1100 ng/dl and about 1400 ng/dl, about 1150 ng/dl and about 1350 ng/dl, and about 1200 ng/dl and about 1300 ng/dl.
- the plasma level of testosterone is maintained, for a Z2 time period, at a level selected from the group consisting of about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, about 1100 ng/dl, about 1150 ng/dl, about 1200 ng/dl, about 1250 ng/dl, about 1300 ng/dl, about 1350 ng/dl, about 1400 ng/dl, about 1450 ng/dl, about 1500 ng/dl, about 1550 ng/dl, about 1600 ng/dl, about 1650 ng/dl, about 1700 mg/ml, about 1750 mg/ml, and about 1800 ng/dl.
- a Z2 time period is at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 12 hours, at least 18 hours, at least 24 hours, at least 36 hours, at least 48 hours, or at least 72 hours.
- the plasma level of testosterone is maintained above the plasma level for testosterone administered via an equivalent intramuscularly administered dose at the same point in time, for a Z3 time period. In another embodiment, the plasma level of testosterone is maintained above therapeutic levels of testosterone for a Z3 time period.
- the plasma level of testosterone is maintained for a Z3 time period after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration, at a value selected from the group consisting of about 300 ng/dl to about 1100 ng/dl, about 350 ng/dl to about 1050 ng/dl, about 400 ng/dl to about 1000 ng/dl, about 450 ng/dl to about 950 ng/dl, about 500 ng/dl to about 900 ng/dl, about 550 ng/dl to about 850 ng/dl, about 600 ng/dl to about 800 ng/dl, about 650 ng/dl to about 750 ng/dl, about 675 ng/dl to about 725 ng/dl and above about 300 ng/dl.
- the plasma level of testosterone is maintained, for a Z3 time period after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration, at a value selected from the group consisting of about 300 ng/dl, about 350 ng/dl, about 400 ng/dl, about 450 ng/dl, about 500 ng/dl, about 550 ng/dl, about 600 ng/dl, about 650 ng/dl, about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, and about 1100 ng/dl.
- a Z3 time period is at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 12 hours, at least 18 hours, at least 24 hours, at least 36 hours, at least 48 hours, or at least 72 hours.
- Multiple treatments may include administration of two or more doses of testosterone (e.g., preservative-free) according to a combination of compositions, devices, and methods encompassed herein.
- the plasma level of testosterone in the Z3 time period is maintained at therapeutically effective levels (e.g, a steady state at or above 300 ng/dl or at or above about 400 ng/dl or other potential values as described hereinabove).
- the plasma level of testosterone in the Z3 time period is maintained at or above a therapeutically effective level while a second dose is administered.
- the plasma level of testosterone in the Z3 time period is maintained above a therapeutically effective level until a second dose is administered.
- the plasma level of testosterone in the Z3 time period is maintained at an elevated level. In an embodiment, the plasma level of testosterone in the Z3 time period is maintained at a level between 300 ng/dl and 700 ng/dl, between 300 ng/dl and 1100 ng/dl, between 300 ng/dl and 1800 ng/dl, between 700 ng/dl and 1100 ng/dl, between 700 ng/dl and 1800 ng/dl, or between 1100 ng/dl and 1800 ng/dl, and/or above about 300 ng/dl, until a second dose is administered, when after the blood levels of testosterone will likely increase again in accordance with well understood pharmacokinetics.
- administration of a testosterone composition as encompassed herein provides a stimulatory effect immediately after injection, such that the plasma level of testosterone is above a plasma therapeutic level of testosterone for a period of time, but not so high as to be toxic to the subject.
- stimulatory levels of plasma testosterone can be detected by measuring the plasma levels of testosterone.
- stimulatory levels of testosterone can be detected by measuring a surrogate for plasma testosterone levels, such as, but not limited to, one or more endocrinology profiles of the subject to which the testosterone was administered.
- endocrinology markers include, but are not limited to, red blood cell proliferation and/or other markers indicative of hormonal function.
- administration of a testosterone composition as encompassed herein provides a stimulatory effect immediately after injection, such that the plasma level of testosterone is above a plasma therapeutic level of testosterone for a period of time, but not so high as to be toxic to the subject. After the plasma levels of testosterone fall from the stimulatory levels, the plasma levels of testosterone are within the therapeutically effective levels as discussed herein.
- administration of a testosterone composition as encompassed herein provides a minimal stimulatory effect immediately after injection, such that the plasma level of testosterone is above a plasma therapeutic level of testosterone for a period of time, but not so high as to be toxic to the subject, after which the plasma levels of testosterone are within the therapeutically effective levels as discussed herein.
- administration of a testosterone composition as encompassed herein provides no stimulatory effect immediately after injection, and the plasma level of testosterone is maintained at a therapeutically effective level as discussed herein.
- testosterone administered to a subject in accordance with the methods of the invention provides pharmacokinetics, including systemic bioavailability, that has diminished pharmacokinetics, including systemic bioavailability, of testosterone when the same dose of testosterone is administered to said subject using needle and syringe, intramuscularly or subcutaneously.
- a formulation was prepared including arachis oil and 10% benzyl alcohol and an active pharmaceutical ingredient based on testosterone. This formulation had a viscosity of 1000 cps.
- An MJ-7 needlefree injection device made by Antares Pharma was used to administer ml of the formulation. The study used the following device power and needle-free syringe orifice settings to achieve needle-free injection of and arachis oil-10% benzyl alcohol solution.
- the injection device was powered with a spring having a spring force of 100 lbs and was equipped with a needle-free syringe having an orifice of 0.36 mm (0.014′′) diameter.
- the injection device was powered with a spring having a spring force of 85 lbs and was equipped with a needle-free syringe having an orifice of 0.28 mm (0.011′′) diameter.
- Intramuscular injections Complete Incomplete, or wet, injections Needle free 40 83% 8 17% Needle and syringe with IM 47 98% 1 2% needle
- the needle bores would be on the same order as the orifices of the needle-free devices.
- Example 2 Comparison of Cavg and Cmax for Various Testosterone Formulations and Methods of Delivery
- the objective of this study was to evaluate the pharmacokinetics of testosterone (Antares QS Autoinjector Device with 10 mm injection depth) when administered via injection to castrated minipigs on Days 1 and 15.
- the test system included minipigs of the Yucatan strain. Castrated male minipigs were obtained from Sinclair Research Center, Inc., Windham, ME. Minipigs were 15 to 20 weeks old, and the target Weight at the initiation of dosing was 20 to 25 kg.
- the Yucatan minipig was chosen as the animal model for this study as it is a preferred non-rodent species for preclinical toxicity testing by regulatory agencies. Housing and care was as specified in the USDA Animal Welfare Act (9 CFR, Parts 1 , 2 , and 3 ) and as described in the Guide for the Care and Use of Laboratory Animals from the National Research Council. The animals were individually housed in swine pens/cages.
- Test material Dose volume 1 3 testosterone, 0.5 ml 100 mg 2 3 testosterone, 0.5 ml 200 mg
- Test articles used for injection of animals included: test article 1, testosterone enanthate at 100 mg/ml in pre-filled syringes; test article 2, testosterone enanthate at 200 mg/ml in pre-filled syringes; test article 3, testosterone enanthate at 100 mg/ml in vials; and test article 4, testosterone enanthate at 200 mg/ml in vials.
- dose material was delivered by a pre-loaded Antares QS Autoinjector Device (see. e.g., co-pending application Ser. No. 61/763,395, which is incorporated by reference).
- dose material was delivered by needle and syringe.
- Test Articles 1 and 2 were administered to the appropriate animals via injection using a mini-needle auto-injector into the scapular region on Day 1 to Test Site 1.
- the animal's dorsal surface area was clipped free of hair with a small animal clipper before the first dose and as often as necessary thereafter to allow for clear visualization of the test site. Care was taken during the clipping procedure to avoid abrasion of the skin.
- Test Articles 3 and 4 were administered to the appropriate animals via intramuscular injection using a 1 mL syringe with a 27 gauge ⁇ 1 inch needle into the proximal portion of the hindlimb to an approximate depth of 3 ⁇ 4 inch on Day to Test Site 2.
- the animal's proximal hindlimb was clipped free of hair with a small animal clipper before the first dose and as often as necessary thereafter to allow for clear visualization of the test site. Care was taken during the clipping procedure to avoid abrasion of the skin.
- the injection site (approximately 2 cm ⁇ 2 cm) was delineated with an indelible marker and remarked as necessary thereafter. Following all Day 22 study observations and bioanalytical sample collection, the animals (including the alternate male pig) were assigned to the exploratory trial phase of this study. The animal's dorsal surface area was clipped free of hair with a small animal clipper before the first dose and as often as necessary thereafter to allow for clear visualization of the test site.
- the QS Autoinjector Device was used to deliver a 0.5 mL dose of dye via injection, into na ⁇ ve scapular area.
- the na ⁇ ve proximal portion of the hindlimb was injected with a 0.5 mL dose of dye via intramuscular injection using a 27 gauge ⁇ 1 inch needle and syringe.
- the injection sites (approximately 2 cm ⁇ 2 cm) were delineated with an indelible marker.
- the animals (including the alternate animal) were subjected to euthanasia and examination. The first day of dosing was designated as Study Day 1.
- An injectable route of exposure was selected because this is the intended route of human exposure.
- An injection depth of 10 mm was investigated as part of this study.
- Dose levels of 100 mg and 200 mg were determined to provide comparison of the intramuscular route of administration via autoinjector and needle and syringe, for toxicokinetic purposes.
- the intramuscular route was selected for further investigation, as this route resulted in less material loss post injection than subcutaneous administration based on macroscopic observations. Doses lower than 100 mg may not have provided necessary circulating concentrations, while doses over 200 mg were not required.
- Dose levels and weekly dose regimen were based on the following supplied reference document “Daily Testosterone and Gonadotropin Levels Are Similar in Azoospermic and Nonazoospermic Normal Men Administered Weekly Testosterone: Implications for Male contraceptive Development” Journal of Andrology Vol. 22, No. 6 November/December 2001.
- the injection sites of each animal were observed on the day of randomization and daily from Days 1 to 22 (at approximately 1 and 4 hours postdose on the days of dosing and once daily on non-dosing days). Particular attention was paid to the injection sites regarding erythema, edema, and any other additional adverse findings.
- the samples were centrifuged at ambient temperature at 1800 ⁇ g. The resulting serum was separated into 3 aliquots of approximately 0.5 mL each for analysis. One aliquot was designated for testosterone and DHT analysis, 1 aliquot for analysis of Sex Hormone Binding Globulin (SHBG), and 1 aliquot for determination of total serum albumin.
- SHBG Sex Hormone Binding Globulin
- the serum samples were transferred into uniquely labeled polypropylene tubes and stored frozen in a freezer set to maintain ⁇ 70° C. Samples to be analyzed were shipped overnight on dry ice to the bioanalytical laboratory for analysis.
- Toxicokinetic parameters were estimated using Watson Laboratory Information Management System (LIMS) and Microsoft Excel. A non-compartmental approach consistent with the subcutaneous and intramuscular route of administration was used for parameter estimation. Individual and mean PK parameters were reported and included Cmax, Tmax, and AUC0-last. When data permitted, the slope of the terminal elimination phase of each concentration versus time curve was determined by log-linear regression, and the following additional parameters were also estimated: AUC0-inf, terminal elimination half-life. All parameters were generated from testosterone (total) concentrations in serum from Days 1 and 15 unless otherwise stated. Parameters were estimated using sampling times relative to the start of each dose administration.
- FIGS. 13 - 19 illustrate, in part, the results of the studies described in Example 3, for various testosterone enanthate concentrations delivered by either auto-injector or traditional needle and syringe methods.
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Anesthesiology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Environmental & Geological Engineering (AREA)
- Medical Informatics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Endocrinology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides compositions and methods for treating a subject in need of treatment with testosterone, including introducing testosterone into the subject subcutaneously, intradermally, or intramuscularly, from a needle assisted jet injection device.
Description
- This application claims priority to U.S. Provisional Patent Application No. 61/621,298, filed Apr. 6, 2012, U.S. Provisional Patent Application No. 61/783,444, filed Mar. 14, 2013, U.S. Provisional Patent Application No. 61/763,395, filed Feb. 11, 2013, and U.S. Provisional Patent Application No. 61/776,283, filed Mar. 11, 2013, all of which are herein incorporated by reference.
- Testosterone is a steroid hormone from the androgen group. In general, androgens promote protein synthesis and growth of those tissues with androgen receptors. Testosterone is anabolic, meaning it builds up bone and muscle mass. Testosterone has the following structural formula:
- The original and primary use of testosterone is for the treatment of males who have too little or no natural endogenous testosterone production—males with hypogonadism. However, over the years, testosterone has also been given for many other conditions, e.g., reducing infertility, correcting lack of libido or erectile dysfunction, correcting osteoporosis, encouraging penile enlargement, encouraging height growth, encouraging bone marrow stimulation, reversing the effects of anemia and appetite stimulation.
- There are several application methods for testosterone, including hypodermic injections and transdermal creams, gels and patches. However, hypodermic injections tend to be painful, inconvenient, and increase the risk of polycythemia. Transdermal creams, gels and patches are often expensive, cause acne and skin irritation at the site of administration, have poor compliance with daily administration, and fail to provide some patients with adequate testosterone levels.
- Accordingly, an urgent need exists for methods of administering testosterone to provide benefits and improvements over conventional methods, e.g., hypodermic injections and transdermal creams, gels and patches, of administering testosterone to patients.
- In one embodiment, the present invention includes an injection device, comprising a housing member having a distal end and a proximal end, a chamber disposed within the housing member configured to hold an amount of a preservative-free medicament comprising testosterone, a needle operatively associated with the chamber and having a length sufficient to deliver the medicament to an injection site at a depth below a patient's skin sufficient to minimize leak-back, a plunger movable within the chamber, and a force generating source capable of providing sufficient force on the plunger to eject at least a portion of the medicament from the chamber through the needle in less than about 20 seconds.
- In another embodiment, the present invention includes a composition comprising testosterone enanthate and sesame oil, the testosterone enanthate being present at a concentration selected from the group consisting of about 50 mg/ml, about 75 mg/ml, about 100 mg/ml, about 125 mg/ml, about 150 mg/ml, about 175 mg/ml, about 200 mg/ml, about 225 mg/ml, and about 250 mg/ml.
- In another embodiment, the present invention includes a composition comprising testosterone enanthate and sesame oil, the testosterone enanthate being present at a concentration selected from the group consisting of about 50 mg/ml, about 75 mg/ml, about 100 mg/ml, about 125 mg/ml, about 150 mg/ml, about 175 mg/ml, about 200 mg/ml, about 225 mg/ml, and about 250 mg/ml, wherein the composition is substantially free of testosterone enanthate precipitate.
- In another embodiment, the present invention includes a method of administering testosterone comprising administering preservative-free composition comprising a unit dose of a testosterone or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration, the plasma level of testosterone is maintained between about 200 ng/dl and about 1800 ng/dl for a Z1 time period.
- In another embodiment, the present invention includes method of administering testosterone comprising administering a preservative-free composition comprising a unit dose of testosterone or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained at a therapeutically effective level for a Z2 time period, (e.g., an extended period of time during treatment).
- These and other objects, features and advantages of the disclosure will be apparent from a consideration of the following non-limiting detailed description considered in conjunction with the drawing figures, in which:
-
FIG. 1 is a side view of an injection device according to an embodiment of the present disclosure; -
FIG. 2 is a cross-sectional view of the injection device ofFIG. 1 in a safety state taken along line A-A; -
FIG. 3 is an enlarged view of a portion of the cross-section shown inFIG. 2 ; -
FIGS. 4A and 4B are perspective views of a safety member used in connection with the injection device ofFIG. 1 ; -
FIG. 5 is an additional cross-sectional view of the device ofFIG. 1 in the safety state; -
FIG. 6A is a cross-sectional view of the injection device ofFIG. 1 in a ready state; -
FIG. 6B is a cross-sectional view of the injection device ofFIG. 1 at the start of an injection state; -
FIG. 6C is a cross-sectional view of the injection device ofFIG. 1 at the end of an injection state; -
FIG. 6D is a cross-sectional view of the injection device ofFIG. 1 in a locked state; -
FIG. 7 is an exploded view of an assembly of the needle guard, sleeve and locking ring associated with the injection device ofFIG. 1 ; -
FIG. 8 is a perspective view of a needle guard according to an embodiment of the injector ofFIG. 1 ; -
FIG. 9 is a cross-sectional view of the cap shown inFIG. 1 ; -
FIG. 10 is a graph showing the pressure within the liquid chamber of an embodiment of an injection device according to the present disclosure, as a function of time; -
FIG. 11 is a cross-sectional view of a needle-free jet injection nozzle; -
FIG. 12 is a graph illustrating an embodiment of the present disclosure in which serum testosterone demonstrates a peak upon injection and subsequently decreases to a therapeutically effective level; -
FIG. 13 is a table illustrating the mean concentrations of testosterone in mini-pig serum; -
FIG. 14 is graph illustrating the serum concentration of testosterone in thegroup 1 mini-pigs ofFIG. 13 ; -
FIG. 15 is graph illustrating the serum concentration of testosterone in thegroup 2 mini-pigs ofFIG. 13 ; -
FIG. 16 is graph illustrating the serum concentration of testosterone for a 0.5 ml auto-injector injection of 200 mg/ml testosterone enanthate in sesame oil; -
FIG. 17 is graph illustrating the serum concentration of testosterone for a 0.5 ml needle and syringe injection of 200 mg/ml testosterone enanthate in sesame oil; -
FIG. 18 is graph illustrating the serum concentration of testosterone for a 0.5 ml auto-injector injection of 100 mg/ml testosterone enanthate in sesame oil; and -
FIG. 19 is graph illustrating the serum concentration of testosterone for a 0.5 ml needle and syringe injection of 100 mg/ml testosterone enanthate in sesame oil. - Throughout the drawings, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components, or portions of the illustrated embodiments. Moreover, while the present disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments and is not limited by the particular embodiments illustrated in the figures.
- With reference to the accompanying drawings, various embodiments of the present invention are described more fully below. Some but not all embodiments of the present invention are explicitly shown. Indeed, various embodiments of the invention may be embodied in many different forms and should not be construed as limited to the embodiments expressly described. Like numbers refer to like elements throughout. The singular forms “a,” “an,” and “the” include the singular and plural unless the context clearly dictates otherwise.
- “Leak back”, as the term is used herein, refers to the leakage of medicament out of an injection site during and/or after injection of a medicament.
- “Substantially no leak back”, as used herein refers an amount of leak back from an injection, the amount being less than about 0.05 ml or less than about 6% of the total volume or less than about 6% of the weight of the medicament. In an embodiment, “substantially no leak back” is an amount of leak back at or below an amount that cannot be readily detected by swiping a finger across the site of injection immediately after the injection has been completed. In an embodiment, “substantially no leak back” is an amount of leak back such that the therapeutic effect of testosterone administered by the injection is not materially altered. By way of non-limiting examples, the amount of leak back can be referenced in a liquid volume of a fluid composition having a specific concentration of testosterone, or the amount of leak back can be referred to in terms of amount of testosterone (e.g., mg testosterone) present in the total leak back volume or the number of injecting patients out of a population that experience leak back.
- To “minimize leak back”, as the term is used herein, is to inhibit or prevent the leak back associated with an injection of medicament, including but not limited to reducing the number of patients experiencing leak back associated with an injection
- A “preservative”, as the term is used herein, refers to compounds known in the art to be used for the purpose of preserving a pharmaceutical composition, such as a medicament. As used herein, the preservative is purposefully used to aid in antimicrobial stability and thus possess antimicrobial activity. Substances not typically considered to be preservatives, or not typically used for preserving other compositions, are not encompassed by this definition.
- “AUC” is the area under a curve representing the concentration of a compound, such as testosterone, or metabolite thereof in the blood or plasma or serum of a patient as a function of time following administration of the compound to the patient. For example, following administration of a testosterone as described herein, the AUC of the testosterone may be determined by measuring the concentration of it or its metabolite in blood using methods such as liquid chromatography-tandem mass spectrometry (LC-MS/MS), at various time intervals, and calculating the area under the blood, plasma or serum concentration-versus-time curve. The concentration versus time curve is sometime referred to as the pharmacokinetic profile. Suitable methods for calculating the AUC from a drug concentration-versus-time curve are well known in the art. Therefore, an AUC for testosterone may be determined by measuring the concentration of testosterone in the blood of a patient following administration of the testosterone to a patient.
- “Bioavailability” refers to the amount of a compound, such as testosterone, that reaches the systemic circulation of a patient following administration of the compound to the patient and can be determined by evaluating, for example, the blood or plasma concentration for the compound.
- “Bioequivalent,” as the term is used herein, refers to one or more of confidence intervals of (a) the maximum concentration of a medicament (e.g., testosterone) in blood plasma of a patient following administration of a dose of the medicament to a patient (“Cmax”) with an injector, (b) the time to reach the maximum concentration of the medicament in blood plasma of a patient following administration of a dose of the medicament to the patient with an injector (“Tmax”), and (c) area under the curve of the concentration of the medicament in blood plasma of a patient following administration of a dose of the medicament to the patient with the injector injected medicament (“AUC”) falls between about 80% and about 125% of the measured confidence interval of the same medicament delivered by an alternative route.
- “Patient” and “Subject” both independently include mammals, such as for example, humans.
- “About” is understood to mean the range of + and −10% of the value referenced. However, use of “about” in reference to a value does not exclude the possibility of the referenced value alone. For example, “about 400” is understood to fully support both “400” as well as “360 to 440.”
- The present disclosure encompasses injector embodiments and compositions and methods suitable for use alone or in combination with the injector embodiments.
- I. Injectors
- Typical hypodermic syringes utilize the force of one or more of a user's fingers pushing to deliver an injection. In some embodiments, powered injectors of the present disclosure are configured to help a subject repeatably and accurately and quickly administer a testosterone formulation to a preset depth at each injection without the need to utilize such pushing force.
- In some embodiments, the powered injector includes an autoinjector, a needle-free jet injector, or a needle-assisted jet injector (collectively referred to as “injectors”).
- Known autoinjector embodiments of powered injectors use an energy source that produces moderate to low pressure in the medicament chamber so that a medicament contained in the medicament chamber is fired at a slow speed, similar to the pressure and speed from a finger-driven syringe. In contrast, autoinjector embodiments of the powered injectors of the present disclosure use an energy source that produces moderate to high pressure in the medicament chamber so that a medicament contained in the medicament chamber is fired at a fast speed and is completely injected into a subject in less than about 10 seconds. Other embodiments of the powered injectors are jet injectors, which can be needle-assisted or needle-free jet injectors. Jet injector embodiments can be configured to have an energy source selected to produce a high pressure in the medicament chamber to eject the medicament with sufficient pressure, force, and speed to exit the injector as a fluid jet. As described in greater detail below, whereas a medicament injected into a subject via an autoinjector or hypodermic syringe is delivered in a bolus typically near the needle tip such that leak back can occur, the medicament delivered from a jet injector is sprayed rapidly into the tissue, typically remotely from the needle tip, and typically does not deposit the medicament in a bolus local to a needle tip such that leak back is minimized Needle-free jet injectors use sufficient pressure and injection speed so that the fluid jet breaks through the outer layer of the skin, depositing the medicament thereunder. Needle-assisted jet injectors can use lower pressures than needle free jet injectors because they employ a needle to break through the outer part of the skin, but have pressures and speeds that are sufficiently high so that the medicament exits the needle tip as a fluid jet.
- Some embodiments of the injectors disclosed herein are single-use or -dose injectors, configured to deliver in a single shot the entire volume of the agent(s) contained within a chamber of the injector or within a cartridge contained within the injector. In other embodiments, the injectors are configured to inject only a portion of the contents of the injector or a cartridge within the injector and can use dosage-setting mechanisms to enable the selection of the volume of injection to be delivered in one shot, or other mechanisms to provide an adjustable dosage. In each of the foregoing embodiments, the injector can be pre-filled, or configured to receive a cartridge that has the dosage of medicament. Alternative embodiments are configured to be fillable as known in the art.
- Injectors provided by the present disclosure may be utilized by patients to self-inject testosterone formulations. Various aspects of the present disclosure relate to self-injection of testosterone formulations by a subject without the aid of a health care provider. In certain embodiments, the injectors use a needle to inject testosterone formulations into a target tissue of a subject, such as autoinjector or needle-assisted jet injector embodiments, while other embodiments are needle-free injectors and thus do not require a needle to inject testosterone formulations into a target tissue of a subject. In certain embodiments, the injectors may utilize pressure sufficient to deliver testosterone formulations completely and quickly. In certain embodiments, the injectors may utilize sufficiently high pressure to deliver one or more testosterone formulations completely and quickly in a fluid jet.
- In some embodiments, powered injectors provided by the present disclosure do not require any priming or preparatory step in order to place them in condition to deliver an injection, thereby reducing or eliminating exposure of the testosterone formulation to the air and/or premature expulsion of the testosterone formulation from a needle of the injector prior to the delivery shot. Therefore, the risk of contact with the testosterone formulation contained in the injector, by the subject or by a non-user of the injectors, is reduced or eliminated.
- A suitable injector for use with the present invention includes the injector shown in co-pending application Ser. No. 61/763,395 entitled “Needle Assisted Jet Injector Device Having Reduced Trigger Force” and Ser. No. 61/776,283 entitled “Needle Assisted Jet Injector Device Having Reduced Trigger Force”, the contents of each which are hereby incorporated by reference in their entirety.
- Referring to
FIGS. 1-5 , an embodiment of an injector according to an embodiment of the present disclosure is presented. The embodiment shown in these figures is a needle injector, and depending on the spring used and delivery conduit, including the needle and injection outlet, can be configured as an autoinjector or a needle-assisted jet injector. The depictedinjector 12 has anouter housing member 14 configured for allowing a user to handle theinjector 12 and that substantially houses most of the components shown inFIG. 2 . In some embodiments,outer housing 14 is formed from twomating portions Housing 14 includes amedicament chamber 22 therein that is configured for storing and dispensing one or more liquid medicaments, such as, for example, a testosterone formulation. In the embodiment shown in FIG. 2,medicament chamber 22 is formed in aprefilled syringe 18 that fits withinhousing 14, but other types of fluid chambers can be used, including known types of cartridges that can be prefilled, refillable, or the like with the medicament(s). Additionally,medicament chamber 22 can be integrally formed withinhousing 14. - In an embodiment, a stopper portion of a prefilled syringe, or other portion of the prefilled syringe designed to assist in containing the medicament contained within the prefilled syringe, is made of a material that is chemically resistant to one or more constituents contained in the prefilled syringe. In an embodiment, a suitable stopper has minimized or reduced leachable or extractable material and/or is resistant to one or more of acids, bases, hydrocarbons, oils, lipids, carbohydrates, or oxygen. Non-limiting examples of suitable stoppers include physically-modified rubber, chemically-modified rubber, teflon, and teflon-coated materials. In an embodiment, a stopper is comprised of any material that enhances the stability of the stopper and/or its function for the containment of an oil-based composition, and in particular, when compared to the function of a standard rubber stopper used to contain the same oil-based composition.
- In the embodiment shown, a
safety member 80 is located on the proximal end ofouter housing 14 and is removably affixed thereto by a plurality of tabs that extend through matching openings formed inouter housing 14 to form a press-fit betweensafety member 80 andouter housing 14.Safety member 80 is configured to prevent or reduce the likelihood of unintended firing of the injection device during, for example, shipping or handling ofinjector 12.Safety member 80 can be removed by a user ofinjector 12 to allow for unrestricted use ofinjector 12. Alternative embodiments of the injectors can be constructed withoutsafety member 80. - In a further embodiment, a
sleeve 16 is housed within and mounted to thehousing 14 and acts as a syringe support member. In some embodiments, thesleeve 16 is configured to hold and position aprefilled syringe 18, carpule or other container of the type known in the art, such as, for example, a BD Hypak™ prefilled syringe (Becton, Dickinson and Company). One example of a suitable prefilled syringe for use in the depicted embodiments is one which is available in various sizes and volumes, such as the Becton Dickinson Hypak™. In some embodiments, the glass of the syringe body can be adhered to the needle. Using a prefilled syringe facilitates handling of the medicament when the injector is assembled, and there is an extensive body of knowledge of how the medicaments keep and behave in a prefilled syringe. In some embodiments,sleeve 16 is substantially fixed to thehousing 12, such as by snaps, an adhesive, a weld, or another known attachment. Theprefilled syringe 18 can have a container portion 20 that defines in its interior amedicament chamber 22, which is prefilled with an injectable medicament such as, for example, a testosterone formulation. In other embodiments, the medicament container and chamber are provided by other structures, such as a chamber that can be integral with or held in the housing,needle hub 32, or other injection outlet portion of the injector, for example. At the distal end of theprefilled syringe 18 is an injection-assistingneedle 24. In certain embodiments, the length ofneedle 24 is less than 5 mm. In one embodiment, the length ofneedle 24 is greater than 5 mm. In one embodiment, the length ofneedle 24 is less than mm. In one embodiment, the length ofneedle 24 is greater than 10 mm. In one embodiment, the length ofneedle 24 is less than 20 mm. In one embodiment, the length ofneedle 24 is greater than 20 mm. In other embodiments, the length ofneedle 24 is about 1 mm, about 2 mm, about 3 mm, about 4, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, about 10 mm, or any range determinable from the preceding lengths (for example, about 4 mm to about 6 mm, or about 8 mm to about 10 mm).Needle 24 has an injectingtip 26 configured as known in the art to penetrate the tissue of a patient which, in some embodiments, is the skin. A needle bore extends through theneedle 24, as known in the art. The bore is in fluid communication with the medicament in themedicament chamber 22 and is open at theneedle tip 26 to inject the medicament. - At a proximal end of the
medicament chamber 22, opposite from theneedle 24, is aplunger 28 that seals the medicament in themedicament chamber 22. In some embodiments, a syringe wall comprises a tubular portion which, in some embodiments, is closed at a distal end and open at a proximal end, to define themedicament chamber 22.Plunger 28 is slideably received in the tubular portion. Theprefilled syringe 18 is configured such that when theplunger 28 is displaced in a distal direction, the volume of themedicament chamber 22 is decreased, forcing the medicament out of thechamber 22 and through the bore ofneedle 24. At the distal end of themedicament chamber 22 is aneedle hub portion 32 to which the needle is mounted. Asyringe flange 35 extends radially from the proximal end of the syringe wall. In injector embodiments that use cartridges, carpules or other containers that define a chamber to contain the medicament, the needle can be fluidly connected with the chamber in a different manner, such as by connecting directly to the cartridge, carpule, or other container, or by connecting to another portion of the injector, such as a housing thereof, by a separate needle hub. - In the embodiment depicted in
FIG. 2 , theprefilled syringe 18 has asyringe body 36 wherein theflange 35, syringe wall, andhub portion 32 is of unitary construction. In some embodiments, the material comprising thesyringe body 36 is glass, but other materials such as, for example, plastic or metal, can be used in other embodiments. To radially position the distal end of theprefilled syringe 18, in someembodiments sleeve 16 has a narrowedbore portion 51 that can be configured to abut the outside of the syringe wall. The narrowed boreportion 51 can be made of a resilient material, such as an elastomer, or it can be made unitarily with the rest ofsleeve 16, such as by a series of radially-aligned, resiliently-flexible fingers. Additionally, the proximal portion of thesyringe 18 can be held in place by a shock-absorbingdevice 33, which, in some embodiments, locates the proximal side of thesyringe body 36 axially, and absorbs shocks from the impact of a sudden firing of theram 60, such as in jet-injector embodiments, which produce elevated pressures in themedicament chamber 22 or container 20. - A trigger mechanism can also be housed within
housing 14. In some embodiments, the trigger mechanism includes aninner housing 54 that can be attached to theouter housing 14, such as by snaps, an adhesive, a weld, or other known attachment.Trigger protrusions 56 extend inwardly from the proximal end of theinner housing 54 and are resiliently biased outwardly.Trigger protrusions 56 are received in arecess 58 ofram 60 in blocking association therewith to prevent distal movement of theram 60 prior to the firing of the device. Theram 60 is moved toward the distal end of the injector 10 by an energy source, which in some embodiments is acompression spring 52, although in other embodiments other suitable energy sources can be used such as elastomer or compressed-gas springs, or a gas generator. An example of acompression spring 52 suitable for use with injectors of the present disclosure is a coil spring. Alternative embodiments can also use other suitable trigger mechanisms as known in the art. - In one embodiment, the invention includes a cammed ram assembly as described in U.S. Pat. No. 13,184,229, which is hereby incorporated by reference in its entirety.
- A
latch housing 64 can be provided exterior to theinner housing 54 to retain thetrigger protrusions 56 in the blocking association in therecess 58 to holdram 60 in the proximal position until firing is actuated.Latch 64 is slideable insideouter housing 14 with respect to theinner housing 54, in some embodiments in an axial direction, and in some embodiments latch 64 surrounds theinner housing 54. In some embodiments latch 64 is free to move relative toouter housing 14 and is only secured in place, after the removal ofsafety member 80, by the pressure exerted thereon bytrigger protrusions 56. In several aspects, nothing is present that biases latchhousing 54 away from the proximal end ofouter housing 14, including springs or the like. Alternative embodiments can use a medicament container that is shuttled forward when the device is activated to pierce the skin with the needle, and some embodiments use trigger mechanisms that are activated by a button on another part of the injector, such as at the proximal end or on a side of the housing as known in the art. - The
housing 14 can have aneedle guard 66 that is moveable with respect to theouter housing 14. In the embodiment of theneedle guard 66 shown inFIG. 2 , theneedle guard 66 is in a protecting position, in which theneedle 24 is disposed within theguard 66. A ridge 65 (FIG. 8 ) abuts an interior surface ofouter housing 14 so as to maintainneedle guard 66 withinhousing 14 whenneedle guard 66 is fully extended into the protecting position. Theneedle guard 66 can be retractable, in some embodiments into theouter housing 14, in a proximal direction to an injecting position, in which theneedle tip 26 and an end portion of theneedle 24 are exposed as shown inFIGS. 6B and 6C for insertion into a patient. In some embodiments, the proximal movement of theguard 66 is prevented at the injecting position. - The
needle guard 66 can be associated with thelatch 64 such that when theguard 66 is displaced proximally it slides thelatch 64 in a proximal direction to release thetrigger protrusions 56 from the recess 58: In some embodiments, thelatch 64 has a latchingportion 68 that abuts theinner housing 54 in an association to bias and maintain thetrigger protrusions 58 positioned in the blocking association with theram 60 prior to the firing of theinjector 12. In some embodiments, when thelatch 64 is slid proximately by the retracting of theguard 66 to the injecting position, the latchingportion 68 slides beyond the portion ofinner housing 54 that it contacts and thetrigger protrusions 56 flex away from therecess 58 of theram 60, allowing thetrigger protrusions 56 to move radially outwardly from therecess 58 and therefore from the blocking association. When this happens,spring 52 biases theram 60 againstplunger 28 to move distally in theinjector 12. - In some embodiments, a
cap 110 can be affixable on the distal end of theinjector 12 so as to coverneedle guard 66 and prevent accidental displacement thereof during shipping or during handling prior to injection.Cap 110 can affix to the distal end ofouter housing 14 by press-fit, screw fit or the like. In certain embodiments,cap 110 can include a pair ofprojections 112 extending inwardly (FIG. 9 ), that form a distally-facingridge 114. In such embodiments,needle guard 66 can be formed with a pair of radially-extending flanges 67 (FIG. 8 ) that are configured to abut thedistal ridge 114 ofprojection 112 to securecap 110 toinjector 12. In some embodiments, the upper edge 116 (FIG. 9 ) ofcap 110 can abut the distal end ofouter housing 14 such thatdistal ridges 114 ofprojection 112 are held againstflanges 67. This arrangement of thecap 110 prevents compression of theneedle guard 66 proximally into the housing, as thecap 110 is juxtaposed between theguard 66 and housing, securingneedle guard 66 in the protecting position to help prevent accidental firing of the injection mechanism. - In some embodiments,
cap 110 can be removed frominjector 12 by twistingcap 110 relative tohousing 14 such thatprojections 112 are moved out of alignment withflanges 67, which allows thecap 110 to be moved distally away fromneedle guard 66. To prevent accidental removal ofcap 110 frominjector 12 due to inadvertent twisting ofcap 110, in some embodiments thecap 110 engages thehousing 14 and/or theneedle guard 66 to require an initially elevated force, such as requiring thecap 110 to snap away from its closed position before completing the rotation to remove thecap 110. For example,upper edge 116 ofcap 110 can be inclined, as shown inFIG. 9 The incline can include a curve, as shown, but generally theedge 116 can have oneedge 118 that is higher than theother edge 120. In some embodiments, the distal end ofouter housing 14 can have a profile that matches that ofupper edge 118 ofcap 110. This arrangement requires deflection ofcap 110 to allow for twisting thereof and increases the force necessary to causecap 110 to twist relative toneedle guard 66. In an alternative embodiment, thecap 110 can have a threaded or cammed association with theflanges 67, or can have another arrangement therewith so that thecap 110 is removed by rotating. -
Cap 110 can be attached toinjector 12 during assembly thereof. This can be done by properly aligningcap 110 and twisting it relative toneedle guard 66 while applying a proximally-directed force thereto such thatprojections 112 move behindflanges 67. Alternatively,flanges 67 can be structured to be deflectable inwardly by disposing them on a correspondingtab 69 formed onneedle guard 66. In such an embodiment,cap 110 can be assembled ontoneedle guard 66 prior to assembly ofspring 72 thereinto, asspring 72 can interfere with the inward deflection offlanges 67. Alternatively,cap 110 can be resiliently deformable to allowcap 110 to be pressed ontoneedle guard 66 such thatprojections 112 pass overflanges 67. - In some embodiments,
needle guard 66 can be resiliently biased distally towards the protecting position bycompression coil spring 72. Also, theneedle guard 66 can have anaxial opening 74 to allow theneedle 24 pass therethrough, and which may be sized according to the type of injector desired. In some embodiments, the construction of theinjector 12 allows a user to push the distal end of theinjector 12 against the patient's skin, pushing theneedle 24 into the skin at an insertion location, substantially at the same speed as theinjector 12 is pushed into the skin. Once theneedle 24 is fully inserted to an insertion point at a desired penetration depth, the trigger mechanism fires causing theinjector 12 to inject the medicament into an injection site. - In some embodiments, such as for subcutaneous injection using a needle-assisted jet injector, the
needle guard 66 can be configured to allow insertion of theneedle 24 to a penetration depth in the skin that is up to about 5 mm below the skin surface. In some embodiments, the penetration depth is about 0.5 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3.0 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, about 5.5 mm, about 6 mm, about 6.5 mm or any range determinable from the preceding depths (for example, about 0.5 mm to about 2.0 mm or about 3.5 mm to about 5.5 mm). In another embodiment, the distance by which theneedle tip 26 extends past theneedle guard 66 or the distal surface of theneedle guard 66 that contacts the skin is up to about 5 mm. In some embodiments, the distance by which theneedle tip 26 extends past theneedle guard 66 or the distal surface of theneedle guard 66 that contacts the skin is about 0.5 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3.0 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, about 5.5 mm, about 6 mm or any range determinable from the preceding depths (for example, about 0.5 mm to about 2.0 mm or about 3.5 mm to about 5.5 mm). - In another embodiment, such as for intramuscular injection using a needle-assisted jet injector, the
injector 12 can be configured to allow theneedle 24 to be inserted into the patient to a penetration depth in the skin, or alternatively beyond the distal surface of theneedle guard 66, by a distance of up to about 20 mm. In some embodiments, theinjector 12 can be configured to allow theneedle 24 to be inserted into the patient to a penetration depth in the skin, or alternatively beyond the distal surface of theneedle guard 66, by a distance of about 0.5 mm, about 1.0 mm, about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3.0 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, about 5.5 mm, about 6 mm, about 6.5 mm, about 7.0 mm, about 7.5 mm, about 8.0 mm, about 8.5 mm, about 9.0 mm, about 9.5 mm, about 10.0 mm, about mm, about 11.0 mm, about 11.5 mm, about 12.0 mm, about 12.5 mm, about 13.0 mm, about 13.5 mm, about 14.0 mm, about 14.5 mm, about 15.0 mm, about 15.5 mm, about 16.0 mm, about 16.5 mm, about 17.0 mm, about 17.5 mm, about 18.0 mm, about 18.5 mm, about 19.0 mm, about 19.5 mm, about 20.0 mm, or any range determinable from the preceding depths (for example, about 0.5 mm to about 20.0 mm or about 3.5 mm to about 15.5 mm). Other exposedneedle 24 lengths can be selected for jet injection to different depths below the skin, with an overall penetration length of between about 0.5 mm and about 20 mm. In these embodiments, theneedle guard 66 can be configured for retracting from a protecting position, in some embodiments covering the entire needle, to an injecting position, in which the desired length of thetip 26 of theneedle 24 is exposed. - In an embodiment, the injection device may comprise a collar surrounding the needle and defining a collar cavity, the collar having a peripheral and forward skin-contacting surface that surrounds, is discontinuous, and is radially spaced from the needle and injection site by an area that is sufficiently large to allow a patient's skin to move into the collar cavity to properly position the needle to penetrate the patient for intradermal delivery of the substance to the injection site to allow spread of the injected substance under the skin while inhibiting or preventing backpressure within the skin from forcing the substance out through the injection site. An example of such an embodiment can be found in U.S. Pat. No. 8,162,886, hereby incorporated by reference in its entirety.
-
Safety member 80 can be removably affixed to the distal end ofouter housing 14 and can include abody portion 84 and a pair of resiliently-flexible legs 82 extending therefrom (FIGS. 4A and 4B ).Legs 82 are configured to extend into corresponding holes orslots 15 formed in the proximal surface ofouter housing 14 and can be shaped to provide a pressure fit withinslots 15 to retainsafety member 80 onhousing 14. Thelegs 82 can be biased outwardly and can further includetabs 86 disposed on the outside surfaces thereof to engage the inside ofouter housing 14 at the location ofslots 15 to further the retention ofsafety member 80 ontoouter housing 14. In some embodiments,legs 82 are shaped to allow a user to remove safety member fromouter housing 14, when injection is desired. In some embodiments, however,legs 82 preventsafety member 80 from becoming accidentally or unintentionally dislodged from its attachment toouter housing 14. -
Legs 82 abut (FIG. 3 ) the proximal-most surface of latchingportion 64 when properly attached toouter housing 14 to hinder or prevent jostling or other motion of latchingportion 64 in the proximal direction, which would cause the injection mechanism to fire. In some embodiments,legs 82 are configured in relationship to thehousing 14 and the trigger mechanism of theinjector 12 such that the force necessary for latchingportion 64 to movelegs 82 out ofslots 15 is sufficient to prevent latchingportion 64 from being jostled out of position due to vibration during shipping or from acute shock during shipping or handling caused by dropping ofinjector 12. Alternative safety members can be used to prevent inadvertent firing of theinjector 12. - In an embodiment in which the
injector 12 is configured as a needle-assisted jet injector, thespring 72 and theprefilled syringe 18 can be configured to jet inject a medicament such as a testosterone formulation. Thus, thespring 72 applies a force on theplunger 28 that can be sufficient to elevate the pressure within themedicament chamber 22 to a level high enough to eject the medicament from theneedle 24 as a fluid jet. In several embodiments, jet injection is an injection of medicament from theneedle tip 26 of theinjector 12 with sufficient velocity and force to drive the medicament to locations remote from theneedle tip 26. - Several jet injector embodiments, whether needle-assisted or needle-free, have an energy source selected to produce a high pressure in the
medicament chamber 22 to eject the medicament therefrom with sufficient force and speed to exit theinjector 12 as a fluid jet. It is believed that jet injectors deliver medicaments rapidly over a wider surface area under the subject's skin, by essentially “spraying” the medicaments into a subject subcutaneously, thereby rapidly exposing a greater surface area of the subject's target tissue to the medicaments. When delivered by an autoinjector, a medicament typically leaves the autoinjector and is deposited locally, since it is not shot remotely from an injection outlet, and is thus delivered in a bolus typically near the needle tip of the autoinjector. This is because an autoinjector requires additional injection time to deliver an injection into resistive media, such as tissue, as opposed to delivery into air. In contrast, embodiments of a powered injector disclosed herein, and in particular embodiments of a disclosed jet injector, display approximately no difference in injection time when injecting into resistive media versus air. Because the medicament delivered by a jet injector is essentially sprayed rapidly into the subject's tissue, typically remotely from the needle tip, the medicament does not leave the jet injector as a single drop or bolus and is thus typically not delivered to a subject as a bolus local to a needle tip. Therefore, by using the jet injectors disclosed herein, a medicament can be dispersed into a subject's tissue more efficiently. Additionally, because jet injectors deliver medicaments via high pressure and speed, the delivered medicaments have a far lower tendency to leak back out of the injection site around the needle or injection track. Therefore, leak-back from the depth the medicament is delivered back toward the injection site, and/or back to the surface of the subject's skin, can be significantly reduced by use of a jet injector. Therefore, when used to deliver one or more medicaments according to the present disclosure, such as, for example, a testosterone formulation, jet injectors significantly reduce the risk of exposure to the medicaments outside of the injection site, thereby reducing the risk of exposure to the medicaments to non-users and to the subject himself, in addition to reliably delivering the entire dose to the desired depth. Preventing or reducing leak-back is beneficial in improving compliance by ensuring that the medicament remains at the injection site at the desired depth. Preventing or reducing leak-back can also be beneficial to keeping medicaments contained to a single area, thereby preventing inadvertent exposure to the subject and/or to other individuals in his vicinity from leak-back to the surface of the skin. Such exposure can include, for example, direct contact with the medicament on the subject's skin or from atomized medicament that may reach the subject or nearby individuals through the air, or through another medium. Additionally, in many cases, patients who use the slow injection of a hand-powered hypodermic syringe or autoinjector risk removing the hand-powered injector from the injection site prematurely, before the shot is completed, leading to exposure of the medicament outside the patient's tissue. In some embodiments, there is substantially no leak-back or no leak-back. In other embodiments, there is no leak-back in about 95% of the injections. In certain embodiments, the amount of leak back is less than about 15% of the total injected volume of medicament, and in other embodiments, when used, the amount of leak back is no more than about 0.05% to about 15% of the total injected volume of medicament, about to about 12.5% of the total injected volume of medicament, about 0.2% to about 10% of the total injected volume of medicament, about 0.3% to about 7.5% of the total injected volume of medicament, about 0.4% to about 5% of the total injected volume of medicament, about 0.5% to about 3% of the total injected volume of medicament, about 0.6% to about 2% of the total injected volume of medicament, or about 0.7% to about 1% of the total injected volume of medicament. In certain embodiments, the amount of leak back is less than about 15% of the total weight of the injected medicament. In certain other embodiments, the amount of leak back is no more than about 0.1% to about 15% of the total weight of the injected medicament, about 0.5% to about 12.5% of the total weight of the injected medicament, about 1% to about 10% of the total weight of the injected medicament, about 2% to about 7.5% of the total weight of the injected medicament, or about 3% to about 5% of the total weight of the injected medicament. - In some embodiments, the
injector 12 is configured, and the injection conducted, to deliver a medicament in a manner to prevent or significantly reduce leak-back and the risk and incidence of undue exposure of the medicament to the air or to the outside surface of the patient's skin. - In some embodiments of needle-assisted jet injectors, short needles can be used to inject medicaments to different parts of the skin, in some embodiments subcutaneously, without any leak-back. Using a
needle 24 that extends about 2.5 mm beyond the distal surface of theneedle guard 66, a 27gauge needle 24, and a pressure in themedicament chamber 22 peaking at about 300 p.s.i. and ending at around 100 p.s.i., resulting in a flow rate of about 0.5 mL/sec, 1 mL of medicament can be successfully be injected without significant leak-back in about 100% of the tested injections as shown, for example, in Table 3 where only slight or measurable, but still slight, wetness at an injection site was observed. Thus, needle-assisted jet injectors of the present disclosure permit jet injection of one or more medicaments using a very short needle reliably, regardless of the thickness of the patient's skin, age, weight or other factors. - In some embodiments, selection of the type of spring as a power source, adjustment of the force delivered by the spring, and/or the manner in which the spring is packaged within the assembled injector can lead to a significant reduction in the amount of time required to deliver a complete injection into a subject, a significant reduction m the spring force required to deliver the injection, and a longer shelf-life. For example, the spring present in many known auto injectors is configured so that a typical injection, in the volume range of about 0.8-1.5 ml, is completely delivered into a subject in 10-15 seconds. Embodiments of the injectors of the present disclosure can have their spring configured so as to deliver a complete injection of about about 1.0 ml in volume in about 1 to about 5 seconds, in some embodiments in about 2 to about 4 seconds, and in some embodiments in about 3 seconds. It is believed that this decrease in time will increase patient compliance when embodiments of the autoinjectors of the present disclosure are used, as less time is required to deliver a complete injection and, thus, the patient will experience less pain.
- Additionally, in some embodiments spring material can be selected so as to only allow a decrease in spring force over the stroke length of the injection as shown. Many known autoinjectors show a decrease in spring force over the course of a single injection of less than approximately 20%. In contrast, embodiments of the injectors of the present disclosure can be configured so that their spring force decreases by at least about 25% over the course of a single injection, in some embodiments from about 25% to about 50% over the course of a single injection, in some embodiments from about 30% to about 50% over the course of a single injection, and in some embodiments by about 50% over the course of a single injection
- Spring material can also be selected, and/or the spring can be set in the injector, so as to not have the spring in an overly compressed state during packaging and shipment of the spring to an end user or patient. This is advantageous because springs that are overly compressed for expended periods of time become over-stressed and show a loss of force over time For example, many known autoinjectors are packaged such that they spend most of their shelf-life with their springs compressed. When packaged in this manner, such known autoinjectors experience a decrease in spring force over time as the autoinjector sits on a shelf awaiting use. In contrast, embodiments of the injectors of the present disclosure can have springs that are made of a material that is sufficiently resilient so as to lose less force over time as it is compressed, and/or can have a spring configured in a fully assembled injector such that it is not in a fully compressed state until the time of injection. In this manner, embodiments of the injectors of the present disclosure lose from about 0% to about 15% of their spring force over a typical shelf life. In some embodiments, the injectors of the present disclosure lose from about 10% to about 12% of their spring force over a three year shelf life.
- In some embodiments of single-shot injectors,
injector 12 includes a disabling mechanism, such as a locking element, which can be provided as a lockingring 70 associated with the injection mechanism. As shown inFIGS. 6A-6D , lockingring 70 can be disposed betweensleeve 16 andneedle guard 66, and can interact withsleeve 16 andneedle guard 66 such that the lockingring 70 only permitsneedle guard 66 to move relative toouter housing 14 through a single injection cycle. This includes movement from the protecting position (FIG. 6A ) into the injecting position (FIGS. 6B, 6C ) and then to return to the protecting position (FIG. 6D ) under the force ofcompression spring 72. Whenneedle guard 16 returns to the protecting position at the end of the injection cycle, locking ring is positioned relative tosleeve 16 andneedle guard 66 such that further movement therebetween is restricted, thus disabling the injector from further making injections and retaining theneedle 24 safely within thehousing 14 of theinjector 12. - As shown in
FIGS. 6A-6D , movement ofneedle guard 66 through one locking cyclecauses locking ring 70 to move relative tosleeve 16 from an injecting position to a locking position. In the injecting position, lockingring 70 is disposed such that theupper arms 71 of lockingring 70 engage a portion of the device that is associated with themedicament chamber 22, such as, for example,proximal notches 92 formed in the outer surface ofsleeve 16. The engagement ofupper arms 71 withinproximal notches 92 releasably maintains lockingring 70 in the injecting position. As shown inFIG. 7 , lockingring 70 can be generally annular in shape so as to surround themedicament chamber 22, either directly or indirectly, such as by surroundingsleeve 16. Lockingring 70 further includes a pair oflower arms 73, each having atab 74 formed on the end thereof. When lockingring 70 is in the injecting position,tabs 74 are received in slot formed inneedle guard 66 such thatneedle guard 66 is slideable through a predetermined distance over lockingring 70. Asneedle guard 66 is moved into the injecting position with respect toouter housing 14,needle guard 66 slides over lockingring 70 such thattabs 74 reach the end ofslot 95 and are depressed inwardly, allowingneedle guard 66 to continue to move into the injecting position. When the injecting position is reached,tabs 74 align withholes 96 ofneedle guard 66, allowinglower arms 73 to return to their natural position, wherein the upper surfaces oftabs 74 engage an edge of theholes 96, thereby coupling lockingring 70 toneedle guard 66. - As
needle guard 66 returns to the protecting position,needle guard 66 pulls distally on lockingring 70, causingupper arms 71 to release fromproximal notches 92. In some embodiments,upper arms 71 andproximal notches 92 are formed with mating inclined surfaces such that the inclined surfaces ofupper arms 71 engage another portion of theinjector 12 that is associated with themedicament chamber 22, such as by extending intoproximal notches 92, but are forced outwardly by distally-directed movement relative thereto. This configuration allows theneedle guard 66 to cause lockingring 70 to move therewith and out of the injecting position asneedle guard 66 moves distally toward the protecting position oversleeve 16, which remains stationary. - When
needle guard 66 reaches the protecting position,upper arms 71 move overdistal notches 93 formed insleeve 16 such that the upper surfaces ofupper arms 71 engage theupper surface 94 ofdistal notches 93. Further, in such a position,flange 77 of lockingring 70 abuts surface 67 of needle guard to blockneedle guard 66 from distal motion relative to lockingring 70. This engagement prevents lockingring 70 from moving proximally with respect tosleeve 16. Because lockingring 70 is coupled toneedle guard 66 in this configuration, and becausesleeve 16 is attached toouter housing 14,needle guard 66 is locked relative toouter housing 14, and is prevented from being moved back into the injecting position. This preventsneedle 24 from being accidentally exposed after use ofinjector 12. Alternative embodiments can use other mechanisms to prevent re-use of the injector or portion thereof. Some embodiments do not employ such a mechanism so that the injector can be reused. In some embodiments, after injection of the medicament, subsequent injection can be prevented automatically and exposure to or contact with remnants of the medicament that may remain on portions of the injector after the injection, such as on a needle tip or jet injection nozzle, can also be prevented or avoided by the construction of theinjector 12. - Referring to
FIG. 11 , a distal end of an embodiment of a needle-free jet injector is shown. The depicted injector can use the systems disclosed herein to fire the injection as described above for the needle injector embodiments, but instead of a needle, ajet nozzle 202 is used to inject the medicament into the subject.Nozzle 202 defines ajet outlet 204 having a diameter selected for causing themedicament 200 to exit thenozzle 202 as a fluid jet that is sufficiently strong to pierce the outer skin layers and to continue to the desired depth of injection. - In an embodiment, an injector may have one or more indicators that that injection of medicament has been completed. In an embodiment, an injector may have one or more indicators that injection of medicament is ongoing. In an embodiment, one or more indicators which independently and distinctively indicate that an injection is ongoing and that an injection has been completed. In an embodiment, a first indicator is different than a second indicator. Indicators can include, but are not limited to, audible indicators, tactile indicators (e.g., a click or a vibration), visual indicators, physical indicators, electronic indicators, or chemical indicators.
- Table 1 shows the results of a trial comparing medicament leak-back that reached the surface of the skin of a subject after injection; data for needle-assisted jet injectors as compared to hand-driven hypodermic syringes is presented. The total number of injections for each group in the trial was 126, and all were administered by a trained health care professional.
-
TABLE 1 Medicament leak-back to the surface of the skin of a subject post injection. % = percent of the total 126 injections administered. Injection site assessment post- Needle-assisted injection jet injector Syringe and needle Site completely dry 89 (71%) 76 (60%) Slight wetness on site 36 (29%) 50 (40%) Measurable wetness, but slight 1 (0%) 0 (0%) (a drop) Considerable wetness at 0 (0%) 0 (0%) injection site - Because jet injectors deliver medicaments rapidly, in some embodiments in less than about 2 seconds, the amount of time patients must hold the injector in their tissue is dramatically decreased as compared to an injection delivered by a typical syringe or autoinjector. It is therefore believed that utilizing jet injectors according to the present disclosure will result in increased patient compliance and adherence to instructions and will therefore result in an increase in correctly administered injected doses. Additionally, the speed at which jet injectors deliver medicaments can further enhance patient compliance with regular injections as the amount of pain experienced by a patient self injecting a medicament will be minimized and, in many cases, may not exist.
- In an embodiment, encompassed herein are a device and method for administering a viscous pharmaceutical formulation to a subject. In an embodiment, a method for administering a viscous pharmaceutical formulation to a subject comprises formulating a pharmaceutical formulation in the form of a solution or suspension having a viscosity of between about 25 and 2500 cps, providing the formulation in a injection device that includes a needle having an insertion length of less than about 10 mm or is needle-free; and administering the formulation from the injection device through an orifice having a diameter of at least about 0.2 mm by jet injection into a subject. In certain embodiments, the viscosity referenced herein can be a dynamic viscosity which can be measured by a Brookfied viscometer. In other embodiments, the viscosity referenced herein can be a kinematic viscosity which is determined by using a capillary viscometer in which a fixed volume of fluid is passed through a small orifice at a controlled temperature under the influence of gravity. In certain embodiments, the viscosity is measured at degrees C. In other embodiments, the viscosity is measured at 25 degrees C.
- In other embodiments, an injectable carrier including an amount of testosterone suspended or dissolved therein has a viscosity between 25 and 300 cps at room temperature (e.g., degrees C.). In certain embodiments, the viscosity is between 90 to 120 cps, in other embodiments the viscosity is about 110 cps. In other embodiments the viscosity is greater than or equal to about 70 cps.
- In certain embodiments, the carrier is coconut oil, soybean oil, sesame oil, castor oil. Other oils include: arachis (peanut) oil, castor oil, cottonseed oil, ethyl oleate, polyoxyethylated castor oil (HCO-60,
polyoxyl 60 hydrogenated castor oil, Cremophor® EL), safflower oil, and soybean oil - In an embodiment, the formulation includes a pharmaceutically suitable oil and is administered from the injection device at a pressure of greater than about 50 psi. In an embodiment, the oil is sesame oil.
- In an embodiment, the injection device has an injection needle with a bore of about mm or about 0.5 mm. Other gauges can also have suitable bores, e.g., 22 gauge, 25 gauge or 27 gauge.
- Referring to the graph shown in
FIG. 10 , numeral 132 represents the point in time when an embodiment ofinjector 12 is fired, and numeral 134 represents the point of completion of injection. In some embodiments, injection is completed when theplunger 28 hits the distal wall of the medicament container 20.Numeral 136 represents the initial and peak pressure during the injection, and numeral 130 represents the final pressure during the injection. In some embodiments, thespring 72 has a linear spring constant and an injection-assistingneedle 24 is used to puncture the skin before commencing the injection. The pressure of injection therefore drops substantially linearly from the start of theinjection 132 until the injection is completed 134 Thefinal pressure 130 at theend 134 of the injection is sufficiently elevated so that even at the end of the firing stroke ofram 60, the medicament is still jet injected, and a very small amount or none of the medicament is deposited in a bolus around theneedle tip 26 - In some embodiments of needle-assisted jet injectors, the
peak pressure 136 during the injection is less than about 1,000 p.s.i., in some embodiments less than 950 p.s.i., in some embodiments less than 900 p.s.i., in some embodiments less than 850 p.s.i., in some embodiments less than 800 p.s.i., in some embodiments less than 750 p.s.i., in some embodiments less than 700 p.s.i., in some embodiments less than 650 p.s.i., in some embodiments less than 600 p.s.i., in some embodiments less than 550 p.s.i., in some embodiments less than 500 p.s.i., in some embodiments less than 450 p.s.i., in some embodiments less than 400 p.s.i., and in some embodiments less than about 350 p.s.i. In some embodiments, at the end of the injection, thepressure 130 applied to the medicament in themedicament chamber 22 can be at least about 80 p.s.i., in some embodiments at least about 90 p.s.i., in some embodiments at least about 100 p.s.i., in some embodiments at least about 150 p.s.i., in some embodiments at least about 200 p.s.i., in some embodiments at least about 250 p.s.i., in some embodiments at least about 300 p.s.i., in some embodiments at least about 350 p.s.i., in some embodiments at least about 400 p.s.i., in some embodiments at least about 450 p.s.i., and in some embodiments at least about 500 p.s.i. In some embodiments, theinitial pressure 136 can be about 330 p.s.i., and thefinal pressure 130 is about 180 p.s.i. In some embodiments, theinitial pressure 136 is about 300 p.s.i., dropping to around 60 p.s.i. at theend 134 of the injection. Other injection rates are used for other embodiments discussed herein. For example, needle-free jet injectors can exert an injection pressure in the range of about 4,000 p.s.i. or greater. Other embodiments of jet injectors utilize lower injection pressures, such as at least about 80 p.s.i. or at least about 60 p.s.i. In contrast, known autoinjectors typically use pressures lower than 60 p.s.i. - The needles used in some embodiments of both autoinjectors and needle-assisted jet injectors are between 26 and 28 gauge, and in some embodiments are around 27 gauge. Other needle gages can also be used where the other components are cooperatively configured to produce the desired injection including, for example, mini-needles. In some embodiments, the components of the
injector 12 can be configured to jet inject one or more medicaments to a subcutaneous injection site. - At about room temperature, in a device having a gauge needle as described herein, in embodiments of needle-assisted jet injectors, injection rates are below about 0.75 mL/sec, in some embodiments below about 0.6 mL/sec, in some embodiments at least about 0.2 mL/sec, in some embodiments at least about 0.3 mL/sec, and in some embodiments at least about 0.4 mL/sec. In some embodiments, the injection rate is selected from below about 0.75 mL/sec, below about 0.7 mL/sec, below about 0.65 mL/sec, below about 0.6 mL/sec, below about 0.55 mL/sec, below about 0.5 mL/sec, below about 0.45 mL/sec, below about 0.4 mL/sec, below about 0.35 mL/sec, below about 0.3 mL/sec, and below about 0.25 mL/sec. In some embodiments, the injection rate is about 0.05 mL/sec, 0.1 mL/sec, about 0.15 mL/sec, about 0.20 mL/sec, about 0.25 mL/sec, about 0.30 mL/sec, about 0.35 mL/sec, about 0.40 mL/sec, about mL/sec, about 0.50 mL/sec, about 0.55 mL/sec, about 0.60 mL/sec, about 0.65 mL/sec, about 0.70 mL/sec, about 0.75 mL/sec, about 0.80 mL/sec, about 0.85 mL/sec, about 0.90 mL/sec, or any range determinable from the preceding injection rates (for example, about 0.05 mL/sec to about 1.5 mL/sec or about 0.70 mL/sec to about 0.75 mL/sec). In embodiments of needle-assisted jet injectors, injection rates are selected from at least about 0.2 ml/sec, at least about 0.25 ml/sec, at least about 0.3 ml/sec, at least about 0.35 ml/sec, at least about 0.4 ml/sec, at least about 0.45 ml/sec, at least about 0.5 ml/sec, at least about 0.55 ml/sec, at least about 0.6 ml/sec, at least about 0.65 ml/sec, and at least about 0.7 ml/sec.
- In some embodiments, the injection of the entire amount of medicament is completed in less than about 15 seconds, in some embodiments in less than about 12 seconds, in some embodiments in less than about 11.5 seconds, in some embodiments in less than about 11.0 seconds, in some embodiments in less than about 10.5 seconds, in some embodiments in less than about 10.0 seconds, in some embodiments in less than about 9.5 seconds, in some embodiments in less than about 9.0 seconds, in some embodiments in less than about 8.5 seconds, in some embodiments in less than about 8.0 seconds, in some embodiments in less than about 7.5 seconds, in some embodiments in less than about 7.0 seconds, in some embodiments in less than about 6.5 seconds, in some embodiments in less than about 6.0 seconds, in some embodiments in less than about 5.5 seconds, in some embodiments in less than about 5.0 seconds, in some embodiments in less than about 4.5 seconds, in some embodiments in less than about 4 seconds, in some embodiments in less than about 3.5 seconds, in some embodiments in less than about 3 seconds, in some embodiments in less than about 2.5 seconds, in some embodiments in less than about 2 seconds, and in some embodiments in less than about 1.5 seconds. In some embodiments, the medicament injection takes at least about 1.0 second, about 1.5 seconds, about 2.0 seconds, about 2.5 seconds, about 3.0 seconds, about 3.5 seconds, about 4.0 seconds, about 4.5 seconds, about 5.0 seconds, about 5.5 seconds, about 6.0 seconds, about 6.5 seconds, about 7.0 seconds, about 7.5 seconds, about 8.0 seconds, about 8.5 seconds, about 9.0 seconds, about 9.5 seconds, about 10.0 seconds, about 10.5 seconds, about 11.0 seconds, about 11.5 seconds, about 12.0 seconds, or any range determinable from the preceding times (for example, about 3.0 seconds to about 8 seconds or about 10 seconds to about 12 seconds).
- In some embodiments, injection of the medicament occurs at about 0.1 mL/sec, completing an injection of 1 mL in about 10 seconds. Other injection rates however, are possible for the alternative embodiments of the
injectors 12 disclosed herein. For example, in some embodiments injector 12 can be configured to deliver a typical flow rate for needle-free jet injection, which can be about 1.5 mL/second, and in some embodiments injector 12 can be configured to deliver a typical flow rate for an autoinjector, which can be about 0.5 mL in 0.3 seconds. - Injection rates can be affected by a number of factors such as, for example, the gauge of the needle used to inject the medicament, the viscosity of the medicament itself, the glide force of the
plunger 28 in the syringe barrel, the temperature of the medicament to be injected, and the temperature of the room in which the injection is administered, as temperature can have a direct effect on viscosity. In various embodiments, tissue resistance does not impact the rate of injection embodiments of the injectors of the present disclosure are capable of achieving. In various aspects, these parameters can be selected and optimized in order to deliver a volume of injection in a desired manner. Such selection and optimization can be readily performed by a person having ordinary skill in the art without undue experimentation. - In an embodiment, an injector may have the capability to heat the testosterone composition contained therein to thereby reduce viscosity and thereby decrease injection time of the composition contained therein. In an embodiment, a heating device is an integral part of the injector. In an embodiment, a heating device is external to the injector. In an embodiment, a heating device has an optional temperature sensing controller. In an embodiment, an injector has one heating device. In an embodiment, an injector has more than one heating device. Non-limiting examples of heating methods and/or devices include electrical, chemical, and exothermic sources.
- In an embodiment, a heating mechanism heats the medicament contained within the injector to a temperature above room temperature. In an embodiment, a heating device heats the medicament contained within the injector to a temperature about 5 degrees C. above room temperature, or about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, or about 50 degrees C. above room temperature (e.g., 20 to 25 degree C.). In one embodiment, the heating mechanism is an electronic, chemical or mechanical heating mechanism. In another embodiment, the mechanism or method of use includes placing a device proximal to a heat source (e.g., under a human arm).
- In an embodiment, a heating device or mechanism further comprises at least one indicia that the heating device is operational, non-operational, and/or at the desired temperature. In an embodiment, a heating device has one or more indicia to indicate to the user that the device has reached a temperature suitable for dispensation of the medicament from the device. In an embodiment, an indicator is a visual indicator. In an embodiment, an indicator is an audible or a tactile indicator
- In some embodiments, a viscous medicament that would otherwise require a longer injection time can still be injected into a subject in the rates set forth above by varying the gauge of the needle. For example, in some embodiments a 26 gauge needle can be utilized with the needle-assisted injectors of the present disclosure to inject a viscous material, in some embodiments a 27 gauge needle can be utilized with the needle-assisted injectors of the present disclosure to inject a viscous material, and in some embodiments a 28 gauge needle can be utilized with the needle-assisted injectors of the present disclosure to inject a viscous material. In each of the foregoing embodiments, the rates of injection are the same as those rates disclosed above. Therefore, by varying the gauge of the needle according to the viscosity of the medicament to be injected, the rates of injection can be maintained. In some embodiments, a 27 gauge needle can be utilized with one or more embodiments of the injectors of the present disclosure to deliver 1.0 ml of an aqueous solution into air in a duration of time from between about 1.0 to about 2.0 seconds, in some embodiments between about 1.5 and about 2.0 seconds, and in some embodiments in about 1.7 seconds. In some embodiments, a 27 gauge needle can be utilized with one or more embodiments of the injectors of the present disclosure to deliver 1.0 ml of an aqueous solution into tissue in a duration of time from between about 1.0 to about 2.0 seconds, in some embodiments between about 1.3 and about 2.0 seconds, in some embodiments in about 1.5 seconds, and in some embodiments in about 1.3 seconds. In some embodiments, a 27 gauge needle can be utilized with one or more embodiments of the injectors of the present disclosure to deliver 1.0 ml of a viscous solution, having a viscosity equivalent to 10% w/w polyethylene glycol 20,000 in water, into air in a duration of time from between about 1.0 to about 5.0 seconds, in some embodiments between about 2.5 and about 5.0 seconds, in some embodiments in about 4.3 seconds, and in some embodiments in about 4.0 seconds. In some embodiments, a 27 gauge needle can be utilized with one or more embodiments of the injectors of the present disclosure to deliver 1.0 ml of a viscous solution, having a viscosity equivalent to 20% w/w polyethylene glycol 20,000 in water, into air in a duration of time from between about to about 15 seconds, in some embodiments between about 12 and about 15 seconds, and in some embodiments in about 14 seconds.
- The cgs physical unit for dynamic viscosity is the poise (P), which is more commonly expressed in ASTM standards as centipoise (cP). Typically, aqueous solutions at 20° C. have a viscosity of approximately 1 cP In several embodiments, injectors of the present disclosure can be configured to produce a flow rate, or a rate of injection, of 0.5 ml/second for aqueous solutions having a cP of, or close to, 1.0, through a 27 gauge needle. In several embodiments, injectors of the present disclosure can be configured to produce a flow rate, or a rate of injection, into skin of 0.5 ml/second for aqueous solutions having a cP of, or close to, 1.0, through a 27 gauge needle.
- U.S. Pat. No. 6,391,003, discloses the experimental results of pressures that can be successfully applied to a medicament in a glass cartridge, using 26 and 27 gauge needles. Table 2 illustrates exemplary injections with different peak pressures that can be used with a needle-assisted jet injector, especially when using a glass, prefilled syringe:
-
TABLE 2 exemplary injections that may be delivered by a needle-assisted jet injector. Pressure and Time (sec.) to Inject 1 cc Pressure 26 Gauge needle 27 Gauge needle 150 p.s.i. 2.1 4.2 200 p.s.i. 1.9 3.9 240 p.s.i. 1.7 3.3 375 p.s.i. 1.4 3.1 - Alternative embodiments can use higher or lower injection pressures. For instance, needle-free injectors may use higher pressures to penetrate the skin without a needle, and autoinjectors will typically use lower pressures to simulate a hand-powered syringe injection.
- II. Other Injectors
- In one or more alternative embodiments, the present disclosure relates to an auto-injector for dispensing a predetermined dosage of a medicament comprising testosterone (e.g., preservative-free), the auto-injector including a housing that is preferably oval or elliptical in shape such that it is more ergonomic. In these alternative embodiments, U.S. Pat. Nos. 7,449,012 and 7,794,432 are hereby incorporated by reference in their entirety. The oval shape prevents the auto-injector from rolling off a table or flat surface, while providing a larger surface area for printing user instructions. A cartridge container is disposed within the housing. A cartridge is received within the cartridge container. The cartridge has at least one opening therein and contains a medicament. The medicament is rearwardly confined by a plunger. The cartridge includes a needle assembly to dispense the medicament therethrough. The cartridge is advanced within the cartridge container from a stored position to an operation position where the needle extends from the cartridge container such that the dose of medicament can be administered. An actuation assembly or power pack provides a stored energy source that is capable of being released to drive the plunger within the cartridge to dispense the medicament through the needle assembly into the user and allowing the needle to be accessible on activation.
- Another aspect of the auto-injector of an alternative embodiment is the provision of a needle cover received within the housing. The needle cover shields the user from inadvertent exposure to the needle after use of the auto-injector providing sharps protection. Theoretically, the operation of the needle cover is fail safe because the cover will not deploy until after the needle penetrates the user. During operation, the needle of the cartridge extends through an opening in the needle cover to permit the dispensing of a dose of medicament. After use of the auto-injector, the needle cover is held in a locked position to prevent the cover from being retracted to expose the needle. According to another aspect of an alternative embodiment, the needle cover has a locked retracted position prior to activation of the auto-injector, thus maintaining a compact configuration of the device prior to use. According to another aspect of an alternative embodiment, the actuation forces associated with the auto-injector are not imparted on the needle cover.
- In accordance with another aspect of an alternative embodiment, the auto-injector has a first locking assembly that holds the needle cover in the first locked position. The first locking assembly may be located on the cartridge container. The first locking assembly may include at least one locking tooth pivotally connected to the cartridge container or the needle cover. Each locking tooth releasably engages the needle cover and includes a locking surface constructed and arranged to contact a surface on the needle cover or the cartridge container. Each locking tooth may be formed as a separate component that is connected to the container or cover. It is contemplated that the locking teeth may be formed as integral parts of the needle cover or cartridge. A spring force of the locking tooth biases the locking surface into contact with the needle cover. The spring force may be provided by a spring portion of the locking tooth. The spring force may also be provided by a separate spring assembly biasing the locking surface into contact with the needle cover. Each locking tooth is preferably pivotally connected to the cartridge container. Each locking tooth pivots in response to movement of the cartridge within the cartridge container. It is also contemplated that the locking teeth can pivot in response to movement of the collet or the power pack. Typically, the locking surface pivots out of contact with the needle cover when the locking tooth pivots in response to the movement of the cartridge. The spring force and the force exerted by the locking teeth on the cartridge are controlled such that they negligibly or minimally impede the motion of the cartridge during the injection operation to avoid any premature rupturing of the diaphragm within the cartridge and premature administering of the medicament.
- In an aspect of an alternative embodiment, the needle cover is spring biased so that the cover is biased outwardly from the housing to cover the exposed needle after the first locking assembly is released. In accordance with another aspect of an alternative embodiment, the auto-injector has a second locking assembly that holds the needle cover in the second locked position. The second locking assembly may be located on the cartridge container, the outer body or the cover member. The second locking assembly may include at least one locking arm or wing preferably connected to the cartridge container. Each locking arm is spaced from the cartridge container such that the locking arm can be temporarily compressed against the cartridge container as the needle cover moves from the first locked position to the second locked position. Each locking arm has a locking surface to engage the needle cover when the needle cover is in the locked extended position. Each locking arm has a thick strut portion and a thin strut portion, wherein the thick strut portion is outwardly curved and the thin strut portion is inwardly curved. This construction maintains the locking arm in a normal uncompressed state to reduce stress on the cartridge container. This also penults a smooth deployment of the cover member. Furthermore, this arrangement ensures that the thick strut portion will buckle into a stable condition. This creates a stronger lock to prevent the cover member from being moved rearwardly to a retracted position. The inwardly curved nature of the thin strut portion allows the thick portion to buckle in a controlled manner to a stable condition. Additionally, the outwardly curved shape of the thick strut portion provides for fail safe locking of the cover member in the extended position. In the event that the thin strut breaks, the thick strut portion will still engage the cover member to maintain it in an extended locked position.
- The cartridge container of an alternative embodiment may further include at least one ledge extending outwardly therefrom. Each ledge is constructed and arranged to engage an edge of an opening in the needle cover to limit the travel of the needle cover with the respect to the cartridge container when the needle cover is in the extended position. When the ledge on the cartridge container engages the edge of the opening, the outward travel of the needle cover is limited. The second locking assembly limits the inward travel of the needle cover. The needle cover and the cartridge container contain openings formed therein. When the openings are aligned prior to activation of the auto-injector, user can view the contents of the cartridge through the housing and the openings. The housing may be transparent or opaque. When opaque, the housing may contain an opening that can be aligned with the openings in the needle cover and cartridge container so that the color of the medicament may be checked to determine whether or not the medicament is suitable for injection. If the medicament is discolored, the user will know not to administer the medicament. When the openings are not aligned after operation of the auto-injector, the user is no longer able to view the contents of the cartridge through the openings providing a visual indication to the user that the auto-injector has been used.
- Another aspect of an alternative embodiment is the construction and arrangement of the actuation assembly or power pack, which is mounted within the housing adjacent to an open end. A release pin or safe pin is removably attached to the actuation assembly to prevent inadvertent actuation of the auto-injector when the release pin is in place. A pin or stem on the release pin is received within an opening in the actuation assembly to prevent actuation of the auto-injector. This opening in the power pack is spaced from the open end of the housing such that the opening is less visible to a user prior to administering the drug. This arrangement is provided so that user will not orient the incorrect end of the auto-injector against the injection surface of the user. The power pack is recessed or spaced from the end of the housing, which provides an indication to the user that pressing the power pack will not operate the auto-injector. The recessed nature of the power pack serves to hide the release pin hole in the power pack when the user is viewing the instructions on the outer body such that the user does not confuse the release pin hole with the opening through which the needle passes for administering the medicament. The release pin includes at least one tab extending therefrom. The tab is compression fit into a complimentary recess formed in the actuation assembly to prevent the inadvertent removal of the release pin. The tabs also prevent rotation of the release pin such that the user easily recognizes that the release pin must be pulled in order to be removed.
- The actuation assembly of an alternative embodiment includes an outer body, which is configured to engage the release pin. The outer body is constructed to be connected to the housing. An inner body is operatively coupled to the outer body. At least one retention tab on the inner body secures the inner body to the outer body. The inner body is capable of limited movement with respect to the outer body. A collet is operatively coupled to the inner body. An energy source is operatively connected to the inner body and the collet. Unlike conventional collets, the collet in the present invention is molded as a single piece. No spacers or other components are provided between the collet and the plunger in the cartridge. This arrangement simplifies construction of an alternative embodiment. Different sized collets can be produced and installed into the actuation assembly, such that only the collet needs to altered when different sized cartridges are used or a different sized dosage of medicament is to be administered.
- III. Medicament Compositions
- In certain embodiments, a medicament of the present invention can be any drug, including testosterone, which can be useful alone or in combination with other embodiments and/or devices encompassed herein. In one embodiment, the drug is testosterone.
- In one embodiment, a testosterone formulation encompassed herein comprises at least one preservative, and in particular, a pharmaceutically-acceptable preservative, and more particularly, a preservative suitable for one or more of intramuscular, subdermal, and subcutaneous administration. Suitable preservatives include, but are not limited to, antimicrobial agents, halogenated alcohols, parabens, and phenylmercuric salts. Non-limiting examples of preservatives include phenol, meta-cresol, benzyl alcohol, methyl paraben, propyl paraben, butyl paraben, benzalkonium chloride, chlorobutanol, thimerosal, phenylmercuric acetate, phenylmercuric borate, and phenylmercuric nitrate.
- In one embodiment, a testosterone formulation encompassed herein does not comprise a preservative or is free of a preservative and in particular, free of a preservative described above. In one embodiment, a preservative-free testosterone formulation encompassed herein comprises testosterone enanthate. In an embodiment, a preservative free testosterone formulation is a unit dose of testosterone or a pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier. In an embodiment, a preservative free testosterone formulation is a multiple of at least two unit doses of testosterone or a pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier. In yet another embodiment, the composition is free or substantially free of precipitate (e.g., testosterone enanthate or testosterone cypionate precipitate).
- In an embodiment, a testosterone formulation (e.g., preservative-free) comprises at least one viscous carrier. In yet another embodiment, a testosterone formulation (e.g., preservative-free) includes testosterone in oil. In an embodiment, a testosterone formulation (e.g., preservative-free) includes testosterone in sesame oil.
- In an embodiment, testosterone in a composition encompassed herein is present in an amount selected from: about 5 mg, about 10 mg, about 15, about 20 mg, about 25 mg, about 30 mg, about 35 mg, about 40 mg, about 45 mg, about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, about 100 mg, about 105 mg, about 110 mg, about 115 mg, about 120 mg, about 125 mg, about 130 mg, about 135 mg, about 140 mg, about 145 mg, about 150 mg, about 155 mg, about 160 mg, about 165 mg, about 170 mg, about 175 mg, about 180 mg, about 185 mg, about 190 mg, about 195 mg, about 200 mg, about 205 mg, about 210 mg, about 215 mg, about 220 mg, about 225 mg, about 230 mg, about 235 mg, about 240 mg, about 245 mg, about 250 mg, about 255 mg, about 260 mg, about 265 mg, about 270 mg, about 275 mg, about 280 mg, about 285 mg, about 290 mg, about 295 mg, about 300 mg, about 305 mg, about 310 mg, about 315 mg, about 320 mg, about 325 mg, about 330 mg, about 335 mg, about 340 mg, about 345 mg, about 350 mg, about 355 mg, about 360 mg, about 365 mg, about 370 mg, about 375 mg, about 380 mg, about 385 mg, about 390 mg, about 395 mg, about 400 mg of medicament or any range determinable from the preceding dosage amounts (for example, about 75 mg to about 150 mg or about 100 mg to about 200 mg). In another embodiment, testosterone is present in an amount greater than about 5 mg.
- As will be understood by the skilled artisan, the amounts of testosterone encompassed herein may be contained within a suitable volume of fluid (e.g., a suitable carrier or oil), based on the method of administration and/or the device used for administration, desired testosterone concentration, etc., among other things. In an embodiment, the amount of medicament contained in and injected from
medicament chamber 22 can be between about 0.02 mL and about 4 mL, in some embodiments less than about 3 mL. In other embodiments, the amount of medicament contained in and injected frommedicament chamber 22 can be about 0.02 mL, about 0.04 mL, about 0.06 mL, about 0.08 mL, about 1.00 mL, about 1.02 mL, about 1.04 mL, about 1.06 mL, about 1.08 mL, about 2.00 mL, about 2.02 mL, about 2.04 mL, about 2.06 mL, about 2.08 mL, about 3.00 mL, about 3.02 mL, about 3.04 mL, about 3.06 mL, about 3.08 mL, about 4.00 mL, about 4.02 mL, about 4.04 mL, about 4.06 mL, about 4.08 mL, about 5.00 mL, or any range determinable from the preceding volumes (for example, about 0.04 mL to about 5.00 mL or about 1.04 mL to about 3.02 mL). Larger volumes may also be selected depending on the particular medicament(s) utilized and dosage required. In some embodiments, e.g., in referenceFIG. 6A , apre-filled syringe 18 containing the desired amount of medicament is assembled into the remaining parts of aninjector 12. In some embodiments, thepre-filled syringe 18 contains from about 0.02 mL to about 4.00 mL of medicament-containing fluid. In some embodiments, thepre-filled syringe 18 contains about 0.02 mL, about 0.04 mL, about 0.06 mL, about 0.08 mL, about 1.00 mL, about 1.02 mL, about 1.04 mL, about 1.06 mL, about 1.08 mL, about 2.00 mL, about 2.02 mL, about 2.04 mL, about 2.06 mL, about 2.08 mL, about 3.00 mL, about 3.02 mL, about 3.04 mL, about 3.06 mL, about 3.08 mL, about 4.00 mL, about 4.02 mL, about 4.04 mL, about 4.06 mL, about 4.08 mL, about 5.00 mL, or any range determinable from the preceding volumes (for example, about 0.04 mL to about 5.00 mL or about 1.04 mL to about 3.02 mL) of one or more medicaments. - In one embodiment, an ester form of testosterone is used. In one embodiment, a testosterone formulation encompassed herein comprises testosterone enanthate and/or testosterone cypionate, collectively referred to herein as “testosterone”. It is understood that alternative compounds that include the testosterone moiety are within the scope of the term “testosterone”, including active metabolites of testosterone.
- In an embodiment, a testosterone formulation encompassed herein is such that it can be administered through a fine-gauge needle, the methods of administration and the devices for administration encompassed and/or described in detail elsewhere herein. A non-limiting example of a fine gauge needle is a 27 gauge needle. However, other examples of fine gauge needles are described in detail elsewhere herein. In an embodiment, a testosterone formulation encompassed herein, when administered in combination with device encompassed herein, a dose can be administered using a force sufficient to smoothly overcome resistance to flow through the syringe body or needle. Methods of determining and optimizing flow rate for injection of a medicament are also described in detail elsewhere herein.
- IV. Methods of Treatment
- The present disclosure provides, in part, a method, device, and composition for treating hypogonadism, reduced infertility, lack of libido or erectile dysfunction, osteoporosis and anemia, a method for encouraging penile enlargement and height growth, and method of stimulating bone marrow and appetite.
- The concentration of testosterone in the blood stream of a subject will depend on the amount of testosterone in the composition administered to the subject as well as the route of administration and the specific formulation used.
- In an embodiment, a subject is treated with a single dose of a composition as encompassed herein. In an embodiment, a subject is treated with two or more doses of a composition as encompassed herein. In an embodiment, a subject is treated with multiple doses of a composition as encompassed herein. In an embodiment, a subject treated with multiple doses is treated for at least one day. In an embodiment, a subject treated with multiple doses is treated for at least one week. In an embodiment, a subject treated with multiple doses is treated for at least one month. In some embodiments, a patient is injected weekly or bi-weekly with one or more testosterone doses. The patient is preferably, but not limited to, being injected in the abdomen or thigh.
- V. Pharmacokinetics
- In an embodiment, a composition comprising testosterone (e.g., a preservative-free testosterone composition) administered to a subject as encompassed herein provides pharmacokinetics, including systemic bioavailability, that has substantially the same (or similar) pharmacokinetics, including systemic bioavailability, of testosterone when the same dose of testosterone is administered to said subject using needle and syringe, intramuscularly or subcutaneously. In another embodiment, the method of treating hypogonadism as encompassed herein comprises introducing into the subcutaneous, intradermal, or intramuscular tissue of a subject, from a needle assisted jet injection device, a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein the pharmacokinetic profile of said testosterone delivered by said needle assisted jet injection device is substantially the same as the pharmacokinetic profile of the same dose of said testosterone when administered to said subject via needle and syringe, intramuscularly or subcutaneously.
- As used herein, the values obtained or calculated for measured testosterone can be in reference to total testosterone, free testosterone, bio-available testosterone or serum testosterone.
- In an embodiment, testosterone administered in accordance with the disclosure encompassed herein achieves comparable, e.g., bioequivalence, pharmacokinetic profile by generating Cmax and Tmax for the same period of time as compared to when the same dose of testosterone is delivered via a needle and syringe, intramuscularly, intradermally, or subcutaneously. In an embodiment, testosterone administered in accordance with the disclosure encompassed herein achieves a pharmacokinetic profile that is superior to that obtained by generating Cmax and Tmax for the same period of time as compared to when the same dose of testosterone is delivered via a needle and syringe, intramuscularly, intradermally, or subcutaneously.
- In an embodiment, a composition comprising testosterone (e.g., a preservative-free composition) administered to a subject in accordance with the methods disclosed herein provides enhanced pharmacokinetics, including systemic bioavailability, of testosterone when the same dose of testosterone is administered to said subject using one of a transdermal cream, gel or patch or needle and syringe, intramuscularly, intradermally, or subcutaneously. In an embodiment, a method of administering testosterone in accordance with the disclosure encompassed herein comprises introducing into the subcutaneous, intradermal, or intramuscular tissue of a subject, from an injector device as encompassed herein and described elsewhere herein, a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein the pharmacokinetic profile of testosterone delivered by the injector device is enhanced relative to the pharmacokinetic profile of the same dose of said testosterone when administered to said subject via one of a transdermal cream, gel or patch or needle and syringe, intramuscularly, intradermally, or subcutaneously. In an embodiment, a method of administering testosterone in accordance with the disclosure encompassed herein comprises introducing into the subcutaneous, intradermal, or intramuscular tissue of a subject, from a needle assisted jet injection device as encompassed herein and described elsewhere herein, a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein the pharmacokinetic profile of testosterone delivered by the needle assisted jet injection device is bioequivalent to the reference-listed drug when administered via needle and syringe, intramuscularly, intradermally, or subcutaneously. In another embodiment, bioequivalent pharmacokinetic profile of testosterone delivered by the needle assisted jet injection device is enhanced as compared to the reference-listed drug when administered via needle and syringe, intramuscularly, intradermally, or subcutaneously.
- In an embodiment of a 5 mg to 400 mg dose of the present disclosure, the pharmacokinetic profile provides a linear increase in testosterone exposure with increases in dose of testosterone administered. In an embodiment, the pharmacokinetic profile provides dose proportional increases in testosterone exposure (AUC and/or Cmax) In another embodiment, the pharmacokinetic profile provides a linear or nonlinear relationship between AUC (ng*h/ml) of testosterone and dose of testosterone when the AUC (ng*h/ml) values are plotted against the corresponding dose values in a Cartesian Plane. In another embodiment, the pharmacokinetic profile provides a linear or nonlinear relationship between Cmax of testosterone and dose of testosterone when the Cmax values are plotted against the corresponding dose values in a Cartesian Plane. Pharmacokinetic information concerning testosterone and a needle assisted jet injector can also be found in co-pending provisional application Ser. No. 61/621,298, the content of which is hereby incorporated by reference in its entirety.
- Accordingly, one embodiment of the present invention provides a method of treating hypogonadism in a subject in need of treatment, said method comprising introducing into the subcutaneous or intramuscular tissue of a patient in need of testosterone, from a needle assisted jet injection device, a composition comprising testosterone (e.g., preservative-free) in a dose ranging from about 5 mg to about 400 mg, wherein said method provides a pharmacokinetic profile whereby testosterone exposure increases linearly in proportion to increases in the dose strength (or level) of testosterone. In an embodiment, the pharmacokinetic profile provides an AUC that increases linearly in proportion to increases in the dose strength (or level) of testosterone administered. In another embodiment, the pharmacokinetic profile provides a Cmax that increases linearly in proportion to increases in testosterone dose level administered.
- For comparison purposes, commercially available testosterone and the associated medication guides and package insert labels of
Androgel 1% (NDA No. 021015), Androgel 1.62% (NDA No. 022309), Testim (NDA No. 021454) and Axiron (NDA No. 022504) can be used, and the package insert labels of each of the foregoing are hereby incorporated by reference in their entirety. - In one embodiment, a method of administering testosterone comprises administering a composition comprising a unit dose of testosterone (e.g., preservative-free) or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained at a therapeutically effective level for a period of time. In one embodiment, a Z1 time period is the time period for which the plasma level of testosterone is maintained at a therapeutically effective level.
- In another embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at a therapeutically effective level starting at about 1 minute after administration and ending at about 1 month after administration. In such an embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at a therapeutically effective level starting at about 2 minutes after administration, or at about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours about 7 hours about 8 hours about 9 hours, about 10 hours, about 11 hours, or about 12 hours after administration, up to about 1 month after administration. In an embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at a therapeutically effective level starting at about 1 minute after administration and ending at about 25 days after administration, about 20 days after administration, about 15 days after administration, about 14 days after administration, about 13 days after administration, about 12 days after administration, about 11 days after administration, about 10 days after administration, about 9 days after administration, about 8 days after administration, about 7 days after administration, about 6 days after administration, about 5 days after administration, about 4 days after administration, about 3 days after administration, about 2 days after administration, about 1 day after administration, or about 0.5 days after administration.
- In one embodiment, a first dose has a first profile and subsequent doses (which may be the same as or different from the first dose) impart different profiles. Depending upon patient response, dose, dose volume and timing of subsequent dosings, the pharmacokinetic profile of a patient can be customized to meet a particular patient's needs through the use of the present invention. In some embodiments, the present invention can be used to maintain therapeutic levels of testosterone during and/or across a prescribed dosing cycle (e.g., once weekly dosing for: 2 weeks, 3 weeks, 4 weeks, 5 weeks, two months, five months, a year, or more).
- In an embodiment, a method of administering testosterone comprises administering a composition comprising a unit dose of a testosterone (e.g., preservative-free) or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration, the plasma level of testosterone is maintained between about 300 ng/dl and about 1100 ng/dl for a time period, “Z1”
- In one embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone between, e.g., about 300 ng/dl and about 1100 ng/dl starting at about 1 minute after administration and ending at about 1 month after administration. In yet another embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone between, e.g., about 300 ng/dl and about 1100 ng/dl starting at about 2 minutes after administration, or at about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours about 7 hours about 8 hours about 9 hours, about 10 hours, about 11 hours, or starting at about 12 hours after administration, up to about 1 month after administration. In an embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone between, e.g., about 300 ng/dl and about 1100 ng/dl starting at about 1 minute after administration and ending at about 25 days after administration, about 20 days after administration, about 15 days after administration, about 14 days after administration, about 13 days after administration, about 12 days after administration, about 11 days after administration, about 10 days after administration, about 9 days after administration, about 8 days after administration, about 7 days after administration, about 6 days after administration, about 5 days after administration, about 4 days after administration, about 3 days after administration, about 2 days after administration, about 1 day after administration, or ending about 0.5 days after administration.
- In an embodiment, the plasma level of testosterone is maintained at a value selected from the group consisting of about 300 ng/dl to about 1100 ng/dl, about 350 ng/dl to about 1050 ng/dl, about 400 ng/dl to about 1000 ng/dl, about 450 ng/dl to about 950 ng/dl, about 500 ng/dl to about 900 ng/dl, about 550 ng/dl to about 850 ng/dl, about 600 ng/dl to about 800 ng/dl, about 650 ng/dl to about 750 ng/dl, and about 675 ng/dl to about 725 ng/dl. In an embodiment, the plasma level of testosterone is maintained at a value selected from the group consisting of about 300 ng/dl, about 350 ng/dl, about 400 ng/dl, about 450 ng/dl, about 500 ng/dl, about 550 ng/dl, about 600 ng/dl, about 650 ng/dl, about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, and about 1100 ng/dl. In an embodiment, the plasma level of testosterone is maintained at a value selected from the group consisting of at least about 300 ng/dl, at least about 350 ng/dl, at least about 400 ng/dl, at least about 450 ng/dl, at least about 500 ng/dl, at least about 550 ng/dl, at least about 600 ng/dl, at least about 650 ng/dl, at least about 700 ng/dl, at least about 750 ng/dl, at least about 800 ng/dl, at least about 850 ng/dl, at least about 900 ng/dl, at least about 950 ng/dl, at least about 1000 ng/dl, at least about 1050 ng/dl, and at least about 1100 ng/dl. In an embodiment, the plasma level of testosterone is maintained at a value selected from the group consisting of about 300 ng/dl or less, about 350 ng/dl or less, about 400 ng/dl or less, about 450 ng/dl or less, about 500 ng/dl or less, about 550 ng/dl or less, about 600 ng/dl or less, about 650 ng/dl or less, about 700 ng/dl or less, about 750 ng/dl or less, about 800 ng/dl or less, about 850 ng/dl or less, about 900 ng/dl or less, about 950 ng/dl or less, about 1000 ng/dl or less, about 1050 ng/dl or less, and about 1100 ng/dl or less.
- In some embodiments, the level of testosterone is maintained as illustrated in
FIG. 12 . In an embodiment, the level of testosterone maintained as illustrated inFIG. 12 is in a mammal. In an embodiment, the level of testosterone maintained as illustrated inFIG. 12 is in the serum of a mammal. In an embodiment, the mammal is a human. - In another embodiment, a method is provided herein for maintaining elevated plasma levels of testosterone in a mammal in need thereof. In certain embodiments, this entails maintaining plasma levels from a subcutaneous dose at or above therapeutic levels (e.g., about 400 ng/dl, about 500 ng/dl, about 600 ng/dl, about 700 ng/dl, about 800 ng./ml, about 900 ng/dl) for an extended period of time. In some embodiments the level is maintained for a period of time that is longer than an intramuscular dose of the same volume and concentration. In an embodiment, the method comprises administering a composition comprising a unit dose of testosterone (e.g., preservative-free) or pharmaceutically acceptable ester or salt thereof in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained at an elevated level of up to about 1800 ng/dl for a period of time. In an embodiment, the time period for which plasma levels of testosterone are maintained at an elevated level is referred to as a “Z2 time period”.
- In some embodiments, the plasma level of testosterone is maintained at an elevated value selected from the group consisting of about 300 ng/dl to about 1800 ng/dl, about 400 ng/dl to about 1800 ng/dl, about 500 ng/dl to about 1800 ng/dl, about 600 ng/dl to about 1800 ng/dl, about 700 ng/dl to about 1800 ng/dl, about 800 ng/dl to about 1800 ng/dl, about 900 ng/dl to about 1800 ng/dl, about 1000 ng/dl to about 1800 ng/dl, about 300 ng/dl to about 1100 ng/dl, about 400 ng/dl to about 1100 ng/dl, about 500 ng/dl to about 1100 ng/dl, about 600 ng/dl to about 1100 ng/dl, about 700 ng/dl to about 1100 ng/dl, about 800 ng/dl to about 1100 ng/dl, about 300 ng/dl to about 1800 ng/dl, about 300 ng/dl to about 1700 ng/dl, about 300 ng/dl to about 1600 ng/dl, about 300 ng/dl to about 1500 ng/dl, about 300 ng/dl to about 1400 ng/dl, about 300 ng/dl to about 1300 ng/dl, about 300 ng/dl to about 1200 ng/dl, about 300 ng/dl to about 1100 ng/dl, about 300 ng/dl to about 1000 ng/dl, about 300 ng/dl to about 900 ng/dl, about 300 ng/dl to about 800 ng/dl, about 300 ng/dl to about 700 ng/dl, about 300 ng/dl to about 600 ng/dl, about 300 ng/dl to about 500 ng/dl, or about 300 ng/dl to about 400 ng/dl.
- In certain embodiments, the blood plasma levels of testosterone are maintained primarily between 400 and 1100 ng/dl, more typically between 400 and 900 ng/dl, during the course of a treatment regimen. In certain embodiments, blood plasma levels at a value between about 400 and about 1000 ng/dl is considered “therapeutically effective,” particularly for steady state maintenance of testosterone levels during a treatment regimen.
- In an embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at an elevated level starting at about 1 minute after administration and ending at about 1 month after administration. In an embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at an elevated level starting at about 2 minutes after administration, or at about 3 minutes, about 4 minutes, about 5 minutes, about 10 minutes, about 20 minutes, about 30 minutes, about 45 minutes, about 60 minutes, about 2 hours, about 3 hours, about 4 hours, about hours, about 6 hours about 7 hours about 8 hours about 9 hours, about 10 hours, about 11 hours, or about 12 hours after administration, up to about 1 month after administration. In an embodiment, a composition encompassed herein, when administered according to the methods and the devices encompassed herein, maintains the plasma level of testosterone at an elevated level starting at about 1 minute after administration and ending at about 25 days after administration, about 20 days after administration, about 15 days after administration, about 14 days after administration, about 13 days after administration, about 12 days after administration, about 11 days after administration, about 10 days after administration, about 9 days after administration, about 8 days after administration, about 7 days after administration, about 6 days after administration, about 5 days after administration, about 4 days after administration, about 3 days after administration, about 2 days after administration, about 1 day after administration, or about 0.5 days after administration.
- In another embodiment, a method is provided herein for obtaining a peak plasma levels of testosterone in a mammal in need thereof. In an embodiment, a method is provided herein, using the compositions and devices encompassed herein, to obtain a peak plasma concentration of testosterone, after which the plasma concentration of testosterone decreases to a therapeutically effective level for a period of time. In another embodiment, a method is provided herein, using the compositions and devices encompassed herein, to obtain a peak plasma concentration of testosterone, after which the plasma concentration of testosterone decreases to an elevated level for a period of time.
- In some embodiments, a peak level of testosterone is in the range of about 400 ng/dl to 2400 ng/dl, 500 ng/dl to 2400 ng/dl, 600 ng/dl to 2400 ng/dl, 700 ng/dl to 2400 ng/dl, 800 ng/dl to 2400 ng/dl, 900 ng/dl to 2400 ng/dl, 1000 ng/dl to 2400 ng/dl, 1100 ng/dl to 2400 ng/dl, 1200 ng/dl to 2400 ng/dl, 1300 ng/dl to 2400 ng/dl, 1400 ng/dl to 2400 ng/dl, 1500 ng/dl to 2400 ng/dl, 1600 ng/dl to 2400 ng/dl, 1700 ng/dl to 2400 ng/dl, 1800 ng/dl to 2400 ng/dl, 1900 ng/dl to 2400 ng/dl, 2000 ng/dl to 2400 ng/dl, 2100 ng/dl to 2400 ng/dl, 2200 ng/dl to 2400 ng/dl, or about 2300 ng/dl to 2400 ng/dl.
- In another embodiment, a method is provided herein, using the compositions and devices encompassed herein, to obtain a peak plasma concentration of testosterone, after which the plasma concentration of testosterone decreases to lower-than-peak level for a period of time, the lower-than-peak level selected from about 300 ng/dl to about 1800 ng/dl, about 400 ng/dl to about 1800 ng/dl, about 500 ng/dl to about 1800 ng/dl, about 600 ng/dl to about 1800 ng/dl, about 700 ng/dl to about 1800 ng/dl, about 800 ng/dl to about 1800 ng/dl, about 900 ng/dl to about 1800 ng/dl, about 1000 ng/dl to about 1800 ng/dl, about 300 ng/dl to about 1100 ng/dl, about 400 ng/dl to about 1100 ng/dl, about 500 ng/dl to about 1100 ng/dl, about 600 ng/dl to about 1100 ng/dl, about 700 ng/dl to about 1100 ng/dl, about 800 ng/dl to about 1100 ng/dl, about 300 ng/dl to about 1800 ng/dl, about 300 ng/dl to about 1700 ng/dl, about 300 ng/dl to about 1600 ng/dl, about 300 ng/dl to about 1500 ng/dl, about 300 ng/dl to about 1400 ng/dl, about 300 ng/dl to about 1300 ng/dl, about 300 ng/dl to about 1200 ng/dl, about 300 ng/dl to about 1100 ng/dl, about 300 ng/dl to about 1000 ng/dl, about 300 ng/dl to about 900 ng/dl, about 300 ng/dl to about 800 ng/dl, about 300 ng/dl to about 700 ng/dl, about 300 ng/dl to about 600 ng/dl, about 300 ng/dl to about 500 ng/dl, or about 300 ng/dl to about 400 ng/dl.
- In an embodiment, a method is provided herein, using the compositions and devices encompassed herein, to obtain a peak plasma concentration of testosterone, in which the peak plasma concentration of testosterone is achieved in about 48 hours, about 36 hours, about 24 hours, about 18 hours, about 12 hours, about 11 hours, about 10 hours, about 9 hours, about 8 hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours about 2 hours, about 1 hours, or about 0.5 hours. In an embodiment, the peak plasma concentration of testosterone is achieved in less than 48 hours, less than 36 hours, less than 24 hours, less than 18 hours, less than 12 hours, less than 11 hours, less than 10 hours, less than 9 hours, less than 8 hours, less than 7 hours, less than 6 hours, less than 5 hours, less than 4 hours, less than 3 hours less than 2 hours, less than 1 hours, or less than 0.5 hours.
- In an embodiment, it was surprisingly found that administration of a testosterone composition as encompassed herein provides a plasma level of testosterone that is maintained at a therapeutically-effective level for a longer period of time than an equivalent dose of testosterone when administered to the same subject via one of a transdermal cream, gel or patch or needle and syringe, intramuscularly, intradermally, or subcutaneously. In an embodiment, at a time post-injection, a testosterone composition as encompassed herein (e.g., preservative-free) maintains a higher plasma concentration of testosterone than would a equivalent testosterone administered to the same subject via one of a transdermal cream, gel or patch or intramuscular injection by needle and syringe over the same time period.
- With reference to the figures and in particular
FIG. 12 , in one embodiment, a method of administering testosterone comprises administering a composition comprising a unit dose of testosterone in a pharmaceutically acceptable carrier subcutaneously to a mammal, wherein after administration the plasma level of testosterone is maintained between about 700 ng/dl and about 1800 ng/dl for a time period, “Z2”, wherein the plasma level of testosterone is also maintained between about 300 ng/dl and about 1100 ng/dl for a time period, “Z3”, which is the time after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration. - In an embodiment, the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at about 1 day post-administration, at about 2 days post-administration, at about 3 days post-administration, at about 4 days post-administration, at about 5 days post-administration, at about 6 days post-administration, at about 7 days post-administration, at about 8 days post-administration, at about 9 days post-administration, at about 10 days post-administration, at about 11 days post-administration, at about 12 days post-administration, at about 13 days post-administration, or at about 14 days post-administration.
- In an embodiment, and with reference to
FIG. 12 , post administration, the plasma level of testosterone is maintained, for a Z2 time period, at or between a level selected from: about 700 ng/dl and about 1800 ng/dl, about 750 ng/dl and about 1750 ng/dl, about 800 ng/dl and about 1700 ng/dl, about 850 ng/dl and about 1650 ng/dl, about 900 ng/dl and about 1600 ng/dl, about 950 ng/dl and about 1550 ng/dl, about 1000 ng/dl and about 1500 ng/dl, about 1050 ng/dl and about 1450 ng/dl, about 1100 ng/dl and about 1400 ng/dl, about 1150 ng/dl and about 1350 ng/dl, and about 1200 ng/dl and about 1300 ng/dl. - In an embodiment, after administration, the plasma level of testosterone is maintained, for a Z2 time period, at a level selected from the group consisting of about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, about 1100 ng/dl, about 1150 ng/dl, about 1200 ng/dl, about 1250 ng/dl, about 1300 ng/dl, about 1350 ng/dl, about 1400 ng/dl, about 1450 ng/dl, about 1500 ng/dl, about 1550 ng/dl, about 1600 ng/dl, about 1650 ng/dl, about 1700 mg/ml, about 1750 mg/ml, and about 1800 ng/dl.
- In an embodiment, a Z2 time period is at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 12 hours, at least 18 hours, at least 24 hours, at least 36 hours, at least 48 hours, or at least 72 hours.
- In an embodiment, the plasma level of testosterone is maintained above the plasma level for testosterone administered via an equivalent intramuscularly administered dose at the same point in time, for a Z3 time period. In another embodiment, the plasma level of testosterone is maintained above therapeutic levels of testosterone for a Z3 time period.
- In yet another embodiment, and with reference to
FIG. 12 , after administration, the plasma level of testosterone is maintained for a Z3 time period after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration, at a value selected from the group consisting of about 300 ng/dl to about 1100 ng/dl, about 350 ng/dl to about 1050 ng/dl, about 400 ng/dl to about 1000 ng/dl, about 450 ng/dl to about 950 ng/dl, about 500 ng/dl to about 900 ng/dl, about 550 ng/dl to about 850 ng/dl, about 600 ng/dl to about 800 ng/dl, about 650 ng/dl to about 750 ng/dl, about 675 ng/dl to about 725 ng/dl and above about 300 ng/dl. - In an embodiment, after administration, the plasma level of testosterone is maintained, for a Z3 time period after the plasma level of an equivalent intramuscularly administered dose drops below the plasma level of the subcutaneously administered dose at the same time point post-administration, at a value selected from the group consisting of about 300 ng/dl, about 350 ng/dl, about 400 ng/dl, about 450 ng/dl, about 500 ng/dl, about 550 ng/dl, about 600 ng/dl, about 650 ng/dl, about 700 ng/dl, about 750 ng/dl, about 800 ng/dl, about 850 ng/dl, about 900 ng/dl, about 950 ng/dl, about 1000 ng/dl, about 1050 ng/dl, and about 1100 ng/dl.
- In an embodiment, a Z3 time period is at least 1 hour, at least 2 hours, at least 3 hours, at least 4 hours, at least 5 hours, at least 6 hours, at least 12 hours, at least 18 hours, at least 24 hours, at least 36 hours, at least 48 hours, or at least 72 hours.
- Multiple treatments may include administration of two or more doses of testosterone (e.g., preservative-free) according to a combination of compositions, devices, and methods encompassed herein. In an embodiment, the plasma level of testosterone in the Z3 time period is maintained at therapeutically effective levels (e.g, a steady state at or above 300 ng/dl or at or above about 400 ng/dl or other potential values as described hereinabove). In an embodiment, the plasma level of testosterone in the Z3 time period is maintained at or above a therapeutically effective level while a second dose is administered. In an embodiment, the plasma level of testosterone in the Z3 time period is maintained above a therapeutically effective level until a second dose is administered. In an embodiment, the plasma level of testosterone in the Z3 time period is maintained at an elevated level. In an embodiment, the plasma level of testosterone in the Z3 time period is maintained at a level between 300 ng/dl and 700 ng/dl, between 300 ng/dl and 1100 ng/dl, between 300 ng/dl and 1800 ng/dl, between 700 ng/dl and 1100 ng/dl, between 700 ng/dl and 1800 ng/dl, or between 1100 ng/dl and 1800 ng/dl, and/or above about 300 ng/dl, until a second dose is administered, when after the blood levels of testosterone will likely increase again in accordance with well understood pharmacokinetics.
- In an embodiment, administration of a testosterone composition as encompassed herein provides a stimulatory effect immediately after injection, such that the plasma level of testosterone is above a plasma therapeutic level of testosterone for a period of time, but not so high as to be toxic to the subject. In an embodiment, stimulatory levels of plasma testosterone can be detected by measuring the plasma levels of testosterone. In another embodiment, stimulatory levels of testosterone can be detected by measuring a surrogate for plasma testosterone levels, such as, but not limited to, one or more endocrinology profiles of the subject to which the testosterone was administered. In an embodiment, endocrinology markers include, but are not limited to, red blood cell proliferation and/or other markers indicative of hormonal function.
- In another embodiment, administration of a testosterone composition as encompassed herein provides a stimulatory effect immediately after injection, such that the plasma level of testosterone is above a plasma therapeutic level of testosterone for a period of time, but not so high as to be toxic to the subject. After the plasma levels of testosterone fall from the stimulatory levels, the plasma levels of testosterone are within the therapeutically effective levels as discussed herein. In an embodiment, administration of a testosterone composition as encompassed herein provides a minimal stimulatory effect immediately after injection, such that the plasma level of testosterone is above a plasma therapeutic level of testosterone for a period of time, but not so high as to be toxic to the subject, after which the plasma levels of testosterone are within the therapeutically effective levels as discussed herein. In an embodiment, administration of a testosterone composition as encompassed herein provides no stimulatory effect immediately after injection, and the plasma level of testosterone is maintained at a therapeutically effective level as discussed herein.
- In an embodiment, testosterone administered to a subject in accordance with the methods of the invention provides pharmacokinetics, including systemic bioavailability, that has diminished pharmacokinetics, including systemic bioavailability, of testosterone when the same dose of testosterone is administered to said subject using needle and syringe, intramuscularly or subcutaneously.
- A formulation was prepared including arachis oil and 10% benzyl alcohol and an active pharmaceutical ingredient based on testosterone. This formulation had a viscosity of 1000 cps. An MJ-7 needlefree injection device made by Antares Pharma was used to administer ml of the formulation. The study used the following device power and needle-free syringe orifice settings to achieve needle-free injection of and arachis oil-10% benzyl alcohol solution.
- For achieving intramuscular injections, the injection device was powered with a spring having a spring force of 100 lbs and was equipped with a needle-free syringe having an orifice of 0.36 mm (0.014″) diameter.
- For achieving subcutaneous injections, the injection device was powered with a spring having a spring force of 85 lbs and was equipped with a needle-free syringe having an orifice of 0.28 mm (0.011″) diameter.
- Results are as follows:
-
TABLE 3 Intramuscular injections. Intramuscular injections Complete Incomplete, or wet, injections Needle free 40 83% 8 17% Needle and syringe with IM 47 98% 1 2% needle -
TABLE 4 Subcutaneous injections Subcutaneous injections Complete Incomplete, or wet, injections Needle free 23 48% 25 52% Needle and syringe with SC 22 46% 26 54% needle - In an embodiment, it will be understood that when mini-needle devices are used instead of needless injection devices, the needle bores would be on the same order as the orifices of the needle-free devices.
- Experimental protocols and references for available data on the Cavg-Cmax can be found in package insert labels of
Androgel 1% (NDA No. 021015), Androgel 1.62% (NDA No. 022309), Testim (NDA No. 021454) and Axiron (NDA No. 022504). -
TABLE 5 Comparison of Cavg and Cmax calculated for Androgel and Testim at various concentrations. Agel Agel Agel Agel Testim Testim 20.25 40.5 60.75 81 50 100 Cav 386 474 513 432 365 612 Cmax 562 715 839 649 538 897 Cmax/Cav 1.455959 1.508439 1.635478 1.502315 1.473973 1.465686 -
TABLE 6 Comparison of Cavg and Cmax calculated for Axiron and testosterone enanthate at various concentrations. AX 60AX 90 AX 120TE 100TE 200Cav 506 415 390 1021 924 Cmax 839 664 658 1299 1315 Cmax/Ca 1.65810 1.6 1.68717 1.27228 1.4231 v 3 9 2 6 - The objective of this study was to evaluate the pharmacokinetics of testosterone (Antares QS Autoinjector Device with 10 mm injection depth) when administered via injection to castrated minipigs on
Days - The test system included minipigs of the Yucatan strain. Castrated male minipigs were obtained from Sinclair Research Center, Inc., Windham, ME. Minipigs were 15 to 20 weeks old, and the target Weight at the initiation of dosing was 20 to 25 kg. The Yucatan minipig was chosen as the animal model for this study as it is a preferred non-rodent species for preclinical toxicity testing by regulatory agencies. Housing and care was as specified in the USDA Animal Welfare Act (9 CFR,
Parts - The experiment was designed as follows:
-
No. of male Group No. animals Test material Dose volume 1 3 testosterone, 0.5 ml 100 mg 2 3 testosterone, 0.5 ml 200 mg - Test articles used for injection of animals included:
test article 1, testosterone enanthate at 100 mg/ml in pre-filled syringes;test article 2, testosterone enanthate at 200 mg/ml in pre-filled syringes; test article 3, testosterone enanthate at 100 mg/ml in vials; and test article 4, testosterone enanthate at 200 mg/ml in vials. - On
Day 1, dose material was delivered by a pre-loaded Antares QS Autoinjector Device (see. e.g., co-pending application Ser. No. 61/763,395, which is incorporated by reference). OnDay 15, dose material was delivered by needle and syringe.Test Articles Day 1 to TestSite 1. The animal's dorsal surface area was clipped free of hair with a small animal clipper before the first dose and as often as necessary thereafter to allow for clear visualization of the test site. Care was taken during the clipping procedure to avoid abrasion of the skin. The injection site (approximately 2 cm×2 cm) was delineated with an indelible marker and remarked as necessary thereafter. Test Articles 3 and 4 were administered to the appropriate animals via intramuscular injection using a 1 mL syringe with a 27 gauge×1 inch needle into the proximal portion of the hindlimb to an approximate depth of ¾ inch on Day toTest Site 2. The animal's proximal hindlimb was clipped free of hair with a small animal clipper before the first dose and as often as necessary thereafter to allow for clear visualization of the test site. Care was taken during the clipping procedure to avoid abrasion of the skin. The injection site (approximately 2 cm×2 cm) was delineated with an indelible marker and remarked as necessary thereafter. Following allDay 22 study observations and bioanalytical sample collection, the animals (including the alternate male pig) were assigned to the exploratory trial phase of this study. The animal's dorsal surface area was clipped free of hair with a small animal clipper before the first dose and as often as necessary thereafter to allow for clear visualization of the test site. The QS Autoinjector Device was used to deliver a 0.5 mL dose of dye via injection, into naïve scapular area. The naïve proximal portion of the hindlimb was injected with a 0.5 mL dose of dye via intramuscular injection using a 27 gauge×1 inch needle and syringe. The injection sites (approximately 2 cm×2 cm) were delineated with an indelible marker. Following dose administration, the animals (including the alternate animal) were subjected to euthanasia and examination. The first day of dosing was designated asStudy Day 1. - An injectable route of exposure was selected because this is the intended route of human exposure. An injection depth of 10 mm was investigated as part of this study. Dose levels of 100 mg and 200 mg were determined to provide comparison of the intramuscular route of administration via autoinjector and needle and syringe, for toxicokinetic purposes. The intramuscular route was selected for further investigation, as this route resulted in less material loss post injection than subcutaneous administration based on macroscopic observations. Doses lower than 100 mg may not have provided necessary circulating concentrations, while doses over 200 mg were not required. Dose levels and weekly dose regimen were based on the following supplied reference document “Daily Testosterone and Gonadotropin Levels Are Similar in Azoospermic and Nonazoospermic Normal Men Administered Weekly Testosterone: Implications for Male contraceptive Development” Journal of Andrology Vol. 22, No. 6 November/December 2001.
- The injection sites of each animal were observed on the day of randomization and daily from
Days 1 to 22 (at approximately 1 and 4 hours postdose on the days of dosing and once daily on non-dosing days). Particular attention was paid to the injection sites regarding erythema, edema, and any other additional adverse findings. - Blood was collected by venipuncture of the vena cava. Samples were collected according to the following table:
-
TK Sample Collection Sample Collection Time Points Schedule Group No. (Time Post Dose) on Days 0 hr 3 hr 6 hr 12 hr 24 hr 48 hr 72 hr 96 hr 168 hr 1 X X X X X X X X 2 X X X X X X X X X = sample to be collected; — = not applicable. (zero hour sample collected before dosing) Target Volume: 3.0 mL Anticoagulant: None Processing: To serum - Blood was collected by venipuncture of the vena cava. Samples were collected according to the following table: Samples were allowed to clot at room temperature for at least minutes before centrifugation.
- The samples were centrifuged at ambient temperature at 1800×g. The resulting serum was separated into 3 aliquots of approximately 0.5 mL each for analysis. One aliquot was designated for testosterone and DHT analysis, 1 aliquot for analysis of Sex Hormone Binding Globulin (SHBG), and 1 aliquot for determination of total serum albumin. The serum samples were transferred into uniquely labeled polypropylene tubes and stored frozen in a freezer set to maintain −70° C. Samples to be analyzed were shipped overnight on dry ice to the bioanalytical laboratory for analysis.
- One set of serum samples was analyzed for concentration of total testosterone using a validated analytical procedure. The samples collected for sex hormone binding globulin (SHBG) and serum albumin will not be analyzed at this time. DHT was not analyzed for this study. Testosterone analysis was performed by LCMS using a method validated under Charles River Study 20027106. Data collection was performed using Analyst from MDS Sciex. Statistical analyses including regression analysis and descriptive statistics including arithmetic means and standard deviations, accuracy and precision were performed using Watson Laboratory Information Management System (LIMS) and Microsoft Excel.
- Toxicokinetic parameters were estimated using Watson Laboratory Information Management System (LIMS) and Microsoft Excel. A non-compartmental approach consistent with the subcutaneous and intramuscular route of administration was used for parameter estimation. Individual and mean PK parameters were reported and included Cmax, Tmax, and AUC0-last. When data permitted, the slope of the terminal elimination phase of each concentration versus time curve was determined by log-linear regression, and the following additional parameters were also estimated: AUC0-inf, terminal elimination half-life. All parameters were generated from testosterone (total) concentrations in serum from
Days -
FIGS. 13-19 illustrate, in part, the results of the studies described in Example 3, for various testosterone enanthate concentrations delivered by either auto-injector or traditional needle and syringe methods. - No animals died during the course of the study. There were no test article-related clinical signs during the study. Sporadic occurrences of scabs, reddened areas, or mechanical injury were noted during the study. These were considered background findings associated with the animal rubbing against the cage or areas that were irritated during dosing procedures while the animals were in the sling. One animal was noted as struggling during dosing on
Day 15; however, this did not appear to affect dose administration. - A small amount of material injected at each test site leaked from the injection site once the device or needle was removed. The amount of leakage was comparable across the sites and animals. Additionally, redness was noted at the injection site after injection across the test sites. There were no additional dermal changes noted during the study interval.
- No test article-related effects on body weight occurred during the study. All animals showed an increase in weight from their starting weight during the study. The results of the trial with the injection of dye in sesame oil resulted in verification of subcutaneous delivery in all animals that received a dose from the QS Autoinjector Device. Conventional administration via needle and syringe administration resulted in intramuscular delivery of the dye, except in 1 animal that had subcutaneous delivery with a dark area in the muscle.
- Each and every reference herein is incorporated by reference in its entirety. The entire disclosure of U.S. Pat. Nos. 8,021,335, 7,776,015, and 6,391,003 and PCT application publication WO 2010/108116 are also hereby incorporated herein by reference thereto as if fully set forth herein.
- It will be appreciated by those skilled in the art that changes could be made to the exemplary embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the exemplary embodiments described, but it is intended to cover modifications within the spirit and scope of the present invention as defined by the claims. For example, specific features of the exemplary embodiments may or may not be part of the claimed invention and features of the disclosed embodiments may be combined.
- It is to be understood that at least some of the figures and descriptions of the invention have been simplified to focus on elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that those of ordinary skill in the art will appreciate may also comprise a portion of the invention. However, because such elements are well known in the art, and because they do not necessarily facilitate a better understanding of the invention, a description of such elements is not provided herein.
- Further, to the extent that the method does not rely on the particular order of steps set forth herein, the particular order of the steps should not be construed as limitation on the claims. The claims directed to the method of the present invention should not be limited to the performance of their steps in the order written, and one skilled in the art can readily appreciate that the steps may be varied and still remain within the spirit and scope of the present invention.
Claims (21)
1. An injection device, comprising:
a housing member having a distal end and a proximal end;
a chamber disposed within the housing member configured to hold an amount of a preservative-free medicament comprising testosterone;
a needle operatively associated with the chamber and having a length sufficient to deliver the medicament to an injection site at a depth below a patient's skin sufficient to minimize leak-back;
a plunger movable within the chamber; and
a force generating source capable of providing sufficient force on the plunger to eject at least a portion of the medicament from the chamber through the needle in less than about 20 seconds.
2. The injection device of claim 1 , wherein the injection site is subcutaneous.
3. The injection device of claim 1 , wherein the force on the plunger is configured to eject at least a portion of the medicament from the chamber through the needle in less than about 15 seconds.
4. The injection device of claim 1 , wherein the force on the plunger is configured to eject all of the medicament from the chamber through the needle in less than about 15 seconds.
5. The injection device of claim 1 , wherein the force on the plunger is configured to eject all of the medicament from the chamber through the needle in less than about 10 seconds.
6. The injection device of claim 1 , wherein the needle length is greater than about mm.
7. The injection device of claim 1 , wherein the needle length is less than about 20 mm.
8. The injection device of claim 1 , wherein the needle length is between about 5 and 12 mm.
9. The injection device of claim 1 , wherein the needle gauge is 27 gauge.
10. The injection device of claim 1 , wherein the needle gauge is 25 gauge to 30 gauge.
11. The injection device of claim 1 , wherein the needle is a thin-walled needle.
12. The injection device of claim 1 , wherein when used, there is substantially no leak-back.
13. The injection device of claim 1 , wherein when used, there is no leak-back.
14. The injection device of claim 1 , wherein when used, there is no leak-back in about 95% of the injections.
15. The injection device of claim 1 , wherein when used, the amount of leak back is less than about 15% of the total injected volume of medicament.
16. The injection device of claim 1 , wherein when used, the amount of leak back is no more than the amount of leak back selected from the group consisting of about 0.05% to about 15% of the total injected volume of medicament, about 0.1% to about 12.5% of the total injected volume of medicament, about 0.2% to about 10% of the total injected volume of medicament, about 0.3% to about 7.5% of the total injected volume of medicament, about 0.4% to about 5% of the total injected volume of medicament, about 0.5% to about 3% of the total injected volume of medicament, about 0.6% to about 2% of the total injected volume of medicament, about 0.7% to about 1% of the total injected volume of medicament.
17. The injection device of claim 1 , wherein when used, the amount of leak back is less than about 15% of the total weight of the injected medicament.
18. The injection device of claim 1 , wherein when used, the amount of leak back is no more than the amount of leak back selected from the group consisting of about 0.1% to about 15% of the total weight of the injected medicament, about 0.5% to about 12.5% of the total weight of the injected medicament, about 1% to about 10% of the total weight of the injected medicament, about 2% to about 7.5% of the total weight of the injected medicament, and about 3% to about 5% of the total weight of the injected medicament.
19. The injection device of claim 1 , further comprising a collar surrounding the needle and defining a collar cavity, the collar having a peripheral and forward skin-contacting surface that surrounds, is discontinuous, and is radially spaced from the needle and injection site by an area that is sufficiently large to allow a patient's skin to move into the collar cavity to properly position the needle to penetrate the patient for intradermal delivery of the substance to the injection site to allow spread of the injected substance under the skin while inhibiting or preventing backpressure within the skin from forcing the substance out through the injection site.
20. An injection device comprising:
a housing;
a cartridge container disposed within the housing;
a cartridge received within the cartridge container, the cartridge having at least one opening therein and containing a medicament comprising testosterone, the medicament rearwardly confined by a plunger, wherein the cartridge includes a needle assembly to dispense the medicament there through, the needle assembly comprising a needle and a non-removable protective needle sheath, the needle having a length sufficient to deliver the medicament to an injection site at a depth below a patient's skin sufficient to minimize leak-back;
an actuation assembly providing a stored energy source capable of being released to drive the needle through the protective needle sheath and to drive the plunger within the cartridge to dispense the medicament through the needle assembly, the stored energy source providing a force sufficient to eject at least a portion of the medicament from the chamber through the needle in less than about 20 seconds;
a needle cover received within the housing, the needle cover having an opening formed therein to permit the passage of the needle assembly there through during a medicament dispensing operation, the needle cover having a first locked position whereby the needle cover is in a locked retracted position prior to activation of the auto-injector, the needle cover having a second locked position whereby the needle cover is in a locked extended position after operation of the auto-injector;
a first locking assembly that holds the needle cover in the first locked position; and
a second locking assembly that holds the needle cover in the second locked position.
21.-48. (canceled)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US18/452,743 US20230390187A1 (en) | 2012-04-06 | 2023-08-21 | Needle assisted jet injection administration of testosterone compositions |
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261621298P | 2012-04-06 | 2012-04-06 | |
US201361763395P | 2013-02-11 | 2013-02-11 | |
US201361776283P | 2013-03-11 | 2013-03-11 | |
US201361783444P | 2013-03-14 | 2013-03-14 | |
US13/857,859 US9950125B2 (en) | 2012-04-06 | 2013-04-05 | Needle assisted jet injection administration of testosterone compositions |
US15/238,901 US20170043103A1 (en) | 2012-04-06 | 2016-08-17 | Needle assisted jet injection administration of testosterone compositions |
US16/149,032 US10821072B2 (en) | 2012-04-06 | 2018-10-01 | Needle assisted jet injection administration of testosterone compositions |
US17/062,196 US11771646B2 (en) | 2012-04-06 | 2020-10-02 | Needle assisted jet injection administration of testosterone compositions |
US18/452,743 US20230390187A1 (en) | 2012-04-06 | 2023-08-21 | Needle assisted jet injection administration of testosterone compositions |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US17/062,196 Continuation US11771646B2 (en) | 2012-04-06 | 2020-10-02 | Needle assisted jet injection administration of testosterone compositions |
Publications (1)
Publication Number | Publication Date |
---|---|
US20230390187A1 true US20230390187A1 (en) | 2023-12-07 |
Family
ID=49301100
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/857,859 Active 2036-09-04 US9950125B2 (en) | 2012-04-06 | 2013-04-05 | Needle assisted jet injection administration of testosterone compositions |
US15/238,901 Abandoned US20170043103A1 (en) | 2012-04-06 | 2016-08-17 | Needle assisted jet injection administration of testosterone compositions |
US16/149,032 Active 2033-06-04 US10821072B2 (en) | 2012-04-06 | 2018-10-01 | Needle assisted jet injection administration of testosterone compositions |
US17/062,196 Active 2034-04-10 US11771646B2 (en) | 2012-04-06 | 2020-10-02 | Needle assisted jet injection administration of testosterone compositions |
US18/452,743 Pending US20230390187A1 (en) | 2012-04-06 | 2023-08-21 | Needle assisted jet injection administration of testosterone compositions |
Family Applications Before (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US13/857,859 Active 2036-09-04 US9950125B2 (en) | 2012-04-06 | 2013-04-05 | Needle assisted jet injection administration of testosterone compositions |
US15/238,901 Abandoned US20170043103A1 (en) | 2012-04-06 | 2016-08-17 | Needle assisted jet injection administration of testosterone compositions |
US16/149,032 Active 2033-06-04 US10821072B2 (en) | 2012-04-06 | 2018-10-01 | Needle assisted jet injection administration of testosterone compositions |
US17/062,196 Active 2034-04-10 US11771646B2 (en) | 2012-04-06 | 2020-10-02 | Needle assisted jet injection administration of testosterone compositions |
Country Status (8)
Country | Link |
---|---|
US (5) | US9950125B2 (en) |
EP (2) | EP4186545A1 (en) |
JP (2) | JP6457383B2 (en) |
KR (1) | KR20150011346A (en) |
CN (1) | CN104487114A (en) |
AU (1) | AU2013203784A1 (en) |
CA (1) | CA2868500C (en) |
WO (1) | WO2013152323A1 (en) |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8496619B2 (en) * | 2011-07-15 | 2013-07-30 | Antares Pharma, Inc. | Injection device with cammed ram assembly |
HUE066268T2 (en) | 2013-02-11 | 2024-07-28 | Antares Pharma Inc | Needle assisted jet injection device having reduced trigger force |
DE102013007389A1 (en) * | 2013-04-30 | 2014-10-30 | Britannia Pharmaceuticals Ltd. | Drug delivery device |
ES2749588T3 (en) * | 2013-10-07 | 2020-03-23 | Antares Pharma Inc | Hematocrit modulation by needle-assisted injection of testosterone |
GB2520008A (en) * | 2013-11-05 | 2015-05-13 | Cambridge Consultants | Injector Device and Base Station |
GB2521212B (en) | 2013-12-13 | 2016-07-27 | Owen Mumford Ltd | Selectable dose injection device |
WO2015108939A1 (en) * | 2014-01-14 | 2015-07-23 | Parenteral Technologies, Llc | Syringe with dosage indicator for the visually impaired |
CA2939791C (en) * | 2014-02-19 | 2021-06-15 | Hermanus L. Jooste | Needle assisted jet injection administration of testosterone compositions |
JP6262031B2 (en) * | 2014-03-11 | 2018-01-17 | テルモ株式会社 | Liquid dosing device |
WO2016025327A1 (en) | 2014-08-10 | 2016-02-18 | Antares Pharma, Inc. | A syringe shock absorber for use in an injection device |
WO2016041872A1 (en) * | 2014-09-15 | 2016-03-24 | Sanofi | Skin-patch type large volume bolus drug injector with medicament pre-heating |
EP3193976A1 (en) | 2014-09-15 | 2017-07-26 | Sanofi | Providing temperature-based feedback regarding delivery of a medicament |
CN107206166B (en) * | 2014-11-12 | 2020-12-04 | 诺和诺德股份有限公司 | Method of manufacturing one of a series of auto-injectors |
CA3009221A1 (en) | 2014-12-23 | 2016-06-30 | Automed Pty Ltd | Delivery apparatus, system and associated methods |
WO2016172182A1 (en) * | 2015-04-24 | 2016-10-27 | Becton, Dickinson And Company | Button safety cap for catheter insertion device |
US20170038184A1 (en) * | 2015-08-06 | 2017-02-09 | Charles E. Ankner | Formulation delivery system |
WO2017035575A1 (en) * | 2015-08-31 | 2017-03-09 | 4C Design Limited | An injector |
US11413399B2 (en) | 2015-11-27 | 2022-08-16 | Sanofi-Aventis Deutschland Gmbh | Injection device with mounting aid for a supplementary device |
WO2019046582A1 (en) * | 2017-08-30 | 2019-03-07 | Antares Pharma, Inc. | Testosterone ester triglyceride formulations |
TWI678221B (en) * | 2017-09-28 | 2019-12-01 | 瑞士商瑞健醫療股份有限公司 | Drive unit |
US20210196890A1 (en) * | 2018-05-24 | 2021-07-01 | Novartis Ag | Automatic Drug Delivery Device |
US11850401B2 (en) | 2018-06-08 | 2023-12-26 | Antares Pharma, Inc. | Auto-insert injector |
KR102051808B1 (en) | 2018-07-23 | 2019-12-04 | 주식회사 종근당 | Stable pharmaceutical composition comprising testosterone undecanoate |
US20210205544A1 (en) * | 2018-09-05 | 2021-07-08 | Shl Medical Ag | Needle guard |
JP7465260B2 (en) * | 2018-09-20 | 2024-04-10 | テバ・ファーマシューティカルズ・インターナショナル・ゲーエムベーハー | Prefilled Syringes and Auto-Injectors |
KR102708503B1 (en) | 2019-02-26 | 2024-09-24 | 벡톤 디킨슨 프랑스 | Rigid needle shield remover with drop test feature for autoinjector |
EP3938013B1 (en) | 2019-03-15 | 2023-09-27 | Eli Lilly and Company | Automatic injection system |
US11957542B2 (en) | 2020-04-30 | 2024-04-16 | Automed Patent Holdco, Llc | Sensing complete injection for animal injection device |
TW202216231A (en) * | 2020-06-11 | 2022-05-01 | 美商亞斯庫拉科技公司 | Device for controlled injection across a variety of material properties |
US11877848B2 (en) | 2021-11-08 | 2024-01-23 | Satio, Inc. | Dermal patch for collecting a physiological sample |
US11964121B2 (en) | 2021-10-13 | 2024-04-23 | Satio, Inc. | Mono dose dermal patch for pharmaceutical delivery |
US12053284B2 (en) | 2021-11-08 | 2024-08-06 | Satio, Inc. | Dermal patch for collecting a physiological sample |
US11452474B1 (en) | 2021-04-14 | 2022-09-27 | Satio, Inc. | Dual lever dermal patch system |
US12048543B2 (en) | 2021-11-08 | 2024-07-30 | Satio, Inc. | Dermal patch for collecting a physiological sample with removable vial |
US12023156B2 (en) | 2021-10-13 | 2024-07-02 | Satio, Inc. | Dermal patch for collecting a physiological sample |
US11510602B1 (en) | 2021-11-08 | 2022-11-29 | Satio, Inc. | Dermal patch for collecting a physiological sample |
WO2023110446A1 (en) * | 2021-12-16 | 2023-06-22 | Shl Medical Ag | Sub-assembly of a medicament delivery device |
Family Cites Families (820)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US547370A (en) | 1895-10-01 | Detachable spout and can-opener | ||
US1465793A (en) | 1923-08-21 | Detachable spout fob containkbs | ||
US1687323A (en) | 1921-07-01 | 1928-10-09 | Cook Lab Inc | Medicament cartridge and hypodermic syringe embodying the same |
US1455793A (en) | 1922-04-07 | 1923-05-22 | Ernest T Kindt | Dowel pin |
US1512294A (en) | 1922-05-02 | 1924-10-21 | Ernest H Marcy | Hypodermic syringe |
US2354649A (en) | 1942-03-04 | 1944-08-01 | Kimble Glass Co | Dental syringe |
GB677523A (en) | 1948-04-13 | 1952-08-20 | Becton Dickinson Co | Discharge structure for hypodermic injection device |
US2699166A (en) | 1949-07-29 | 1955-01-11 | Becton Dickinson Co | Hypodermic injection unit |
US2717601A (en) | 1949-08-10 | 1955-09-13 | Frederick M Turnbull | Syringe ampule |
US2737946A (en) | 1949-09-01 | 1956-03-13 | Jr George N Hein | Hypodermic injection apparatus |
US2648334A (en) | 1949-10-28 | 1953-08-11 | Turnbull | Hypodermic injection assembly |
US2645223A (en) | 1951-02-17 | 1953-07-14 | Becton Dickinson Co | Injection device |
US2607344A (en) | 1951-08-01 | 1952-08-19 | Frederick M Turnbull | Syringe assembly |
US2728341A (en) | 1951-11-05 | 1955-12-27 | Zbislaw M Roehr | Hypodermic syringe |
US2687730A (en) | 1951-12-04 | 1954-08-31 | Jr George N Hein | Ampoule |
US2688967A (en) | 1953-06-02 | 1954-09-14 | Huber Jennie | Metal aspirating syringe |
US2893390A (en) | 1954-04-28 | 1959-07-07 | Edgar H Wilburn | Hypodermic syringes |
DK97473C (en) | 1954-10-27 | 1963-12-02 | Astra Apotekarnes Kem Fab | Operating mechanism for automatic syringes. |
US2813528A (en) | 1956-02-13 | 1957-11-19 | Omega Prec Medical Instr Co In | Hypodermic syringe |
US2866458A (en) | 1956-05-09 | 1958-12-30 | Becton Dickinson Co | Hypodermic assembly |
US2888924A (en) | 1958-02-25 | 1959-06-02 | Russell P Dunmire | Hypodermic syringes |
US3130724A (en) | 1962-05-07 | 1964-04-28 | Roehr Products Company Inc | Syringe structure |
US3375825A (en) | 1965-09-02 | 1968-04-02 | Becton Dickinson Co | Prefilled syringe |
US3382865A (en) | 1965-10-18 | 1968-05-14 | Ashton L. Worrall Jr. | Device for taking multiple blood samples or the like |
US3526225A (en) | 1967-03-31 | 1970-09-01 | Tokyo Sokuhan Kk | Jet-type hypodermic injection device |
GB1181037A (en) | 1968-05-31 | 1970-02-11 | Glover Lab Proprietary Ltd J | Disposable Hypodermic Syringe |
US3563098A (en) | 1968-06-28 | 1971-02-16 | Rex Chainbelt Inc | Automatic quick release mechanism |
DE1957833A1 (en) | 1968-11-21 | 1970-07-02 | Maurice Steiner | Injection syringe, especially injection syringe handled by the patient himself |
US3557784A (en) | 1968-12-24 | 1971-01-26 | Walter A Shields | Syringe |
GB1216813A (en) | 1969-02-21 | 1970-12-23 | Shozo Narusawa | Transcutaneous injection device |
US3605744A (en) | 1969-04-22 | 1971-09-20 | Edward M Dwyer | Injection apparatus and method of injecting |
US3831814A (en) | 1969-07-25 | 1974-08-27 | Cutter Lab | Trocar-cannula |
BE755224A (en) | 1969-08-25 | 1971-02-24 | Philips Nv | INJECTION SYRINGE |
US3688765A (en) | 1969-10-03 | 1972-09-05 | Jack S Gasaway | Hypodermic injection device |
JPS501001B1 (en) | 1969-10-14 | 1975-01-14 | ||
JPS5016490B1 (en) | 1970-02-19 | 1975-06-13 | ||
US3702509A (en) | 1970-09-08 | 1972-11-14 | Joseph G Zowaski | Trenching machine with tapered buckets |
US3848593A (en) | 1970-10-09 | 1974-11-19 | Affiliated Hospital Prod | Side loading disposable carpule syringe |
JPS5033792B1 (en) | 1970-12-16 | 1975-11-04 | ||
JPS5026411B1 (en) | 1970-12-24 | 1975-09-01 | ||
US3712301A (en) | 1971-01-11 | 1973-01-23 | Survival Technology | Gun type hypodermic injector with rapid cartridge displacement within holder |
JPS5044625Y2 (en) | 1971-01-26 | 1975-12-18 | ||
US3797491A (en) | 1971-02-11 | 1974-03-19 | Ampoules Inc | Method of performing an intramuscular injection |
US3770026A (en) | 1971-09-17 | 1973-11-06 | J Isenberg | Apparatus and method for accurately loading syringes |
BE795162A (en) | 1972-02-10 | 1973-08-08 | Philips Nv | INJEKTIE-INRICHTING |
US3811441A (en) | 1972-02-10 | 1974-05-21 | Survival Technology | Cartridge syringe |
JPS5112330B2 (en) | 1972-07-24 | 1976-04-19 | ||
US3790048A (en) | 1972-07-28 | 1974-02-05 | Ortho Pharma Corp | Incremental dose dispenser |
JPS4970282U (en) | 1972-10-06 | 1974-06-19 | ||
JPS4970286U (en) | 1972-10-09 | 1974-06-19 | ||
JPS5333322Y2 (en) | 1972-11-09 | 1978-08-17 | ||
JPS5039135B2 (en) | 1972-11-11 | 1975-12-15 | ||
JPS4990151U (en) | 1972-11-22 | 1974-08-05 | ||
JPS5637323Y2 (en) | 1972-11-30 | 1981-09-01 | ||
FR2237643B1 (en) | 1973-07-17 | 1978-03-17 | Steiner Maurice | |
US3882863A (en) | 1973-08-01 | 1975-05-13 | Survival Technology | Hypodermic injection device having cannula covered with resilient sheath |
JPS5039135U (en) | 1973-08-07 | 1975-04-22 | ||
US3946732A (en) | 1973-08-08 | 1976-03-30 | Ampoules, Inc. | Two-chamber mixing syringe |
JPS5044625U (en) | 1973-08-24 | 1975-05-06 | ||
US3895633A (en) | 1973-09-27 | 1975-07-22 | Survival Technology | Large capacity syringe |
JPS547329Y2 (en) | 1973-10-17 | 1979-04-06 | ||
JPS5327592Y2 (en) | 1973-11-05 | 1978-07-12 | ||
JPS5522293Y2 (en) | 1973-12-06 | 1980-05-28 | ||
JPS5425131Y2 (en) | 1974-07-15 | 1979-08-23 | ||
JPS545103Y2 (en) | 1974-07-16 | 1979-03-05 | ||
SE7502318L (en) | 1975-03-03 | 1976-09-06 | Af Ekenstam Thuresson Bo | PACKAGING FOR LIQUID FOR SEMI-SOLID MATERIAL, SUITABLE FOR SMALLER QUANTITIES |
AT341649B (en) | 1975-08-07 | 1978-02-27 | Immuno Ag | INJECTION SYRINGE |
US4181721A (en) * | 1975-10-27 | 1980-01-01 | Schering Aktiengesellschaft | Depot preparations in an oily, unsaturated solution for intramuscular injection |
US4031893A (en) | 1976-05-14 | 1977-06-28 | Survival Technology, Inc. | Hypodermic injection device having means for varying the medicament capacity thereof |
US4127118B1 (en) | 1977-03-16 | 1995-12-19 | Alvaro Latorre | Method of effecting and enhancing an erection |
US4171698A (en) | 1977-08-15 | 1979-10-23 | Abbott Laboratories | Prefilled two-compartment syringe |
US4222392A (en) | 1979-05-23 | 1980-09-16 | Alier-Screen, Inc. | Allergy testing device with vented base |
US4227528A (en) | 1978-12-26 | 1980-10-14 | Wardlaw Stephen C | Automatic disposable hypodermic syringe |
DE2929425A1 (en) | 1979-07-20 | 1981-02-12 | Lothar Kling | DEVICE FOR INJECTION SYRINGES FOR INTRAMUSCULAR AND SUBENTANE INJECTION |
US4258713A (en) | 1979-07-23 | 1981-03-31 | Wardlaw Stephen C | Automatic disposable hypodermic syringe |
US4338980A (en) | 1980-01-14 | 1982-07-13 | Schwebel Paul R | Device for filling medicament injectors |
US4316643A (en) | 1980-03-25 | 1982-02-23 | The General Tire & Rubber Co. | Vehicle suspension bushing |
US4328802A (en) | 1980-05-14 | 1982-05-11 | Survival Technology, Inc. | Wet dry syringe package |
US4411661A (en) | 1980-10-22 | 1983-10-25 | Travenol European Research And Development Centre | Spike connector |
US4316463A (en) | 1981-01-26 | 1982-02-23 | Vac-O-Cast, Inc. | Corrosive protected hypodermic module |
US4333456A (en) | 1981-02-09 | 1982-06-08 | Sterling Drug Inc. | Self-aspirating hypodermic syringe and self-aspirating assembly therefor |
US4333458A (en) | 1981-02-09 | 1982-06-08 | Sterling Drug Inc. | Self-aspirating syringe with positively engaged locking collet |
FR2506161A1 (en) | 1981-05-20 | 1982-11-26 | Alsetex Armement | Self:injection syringe with compartments for specific liquids - is spring:loaded first to penetrate patient then inject liq.(s), is automatic |
ATE32432T1 (en) | 1981-08-10 | 1988-02-15 | Duphar Int Res | AUTOMATIC INJECTION SYRINGE. |
US4378015A (en) | 1981-12-21 | 1983-03-29 | Wardlaw Stephen C | Automatic injecting syringe |
US4558690A (en) | 1982-01-26 | 1985-12-17 | University Of Scranton | Method of administration of chemotherapy to tumors |
EP0103664B1 (en) | 1982-08-25 | 1986-12-30 | Wagner, Wolfgang, Dr.med. | Device for injection by the effect of vacuum on the skin |
ATE23802T1 (en) | 1982-10-27 | 1986-12-15 | Duphar Int Res | AUTOMATIC INJECTION DEVICE. |
FR2539302B1 (en) | 1983-01-17 | 1986-03-14 | Brunet Jean Louis | SYRINGE FOR MEDICAL USE |
US4484910A (en) | 1983-12-21 | 1984-11-27 | Survival Technology, Inc. | Dual mode automatic injector |
US4592745A (en) | 1984-02-29 | 1986-06-03 | Novo Industri A/S | Dispenser |
US5078680A (en) | 1984-08-08 | 1992-01-07 | Survival Technology, Inc. | Automatic injector for emergency treatment |
US4678461A (en) | 1984-11-01 | 1987-07-07 | Survival Technology, Inc. | Automatic injector with improved glass container protector |
EP0186916B1 (en) | 1984-11-02 | 1988-12-21 | Duphar International Research B.V | Automatic injection device |
FR2635009B2 (en) | 1984-11-20 | 1990-11-09 | Poutrait Morin | DEVICE FOR RETAINING A HYPODERMIC SYRINGE BULB IN THE CASE |
US4634027A (en) | 1985-01-04 | 1987-01-06 | Mvm Valve Co., Inc. | Liquid dispensing apparatus and an anti-drip valve cartridge therefor |
DE3673317D1 (en) | 1985-10-11 | 1990-09-13 | Duphar Int Res | AUTOMATIC SYRINGE. |
JPH0613052B2 (en) | 1985-11-08 | 1994-02-23 | デイゼトロニツク アクチエンゲゼルシヤフト | Injection device |
US4662878A (en) | 1985-11-13 | 1987-05-05 | Patents Unlimited Ltd. | Medicine vial adaptor for needleless injector |
IE59361B1 (en) | 1986-01-24 | 1994-02-09 | Akzo Nv | Pharmaceutical preparation for obtaining a highly viscous hydrogel or suspension |
US4664653A (en) | 1986-02-24 | 1987-05-12 | Sagstetter William E | Manually operated reusable injection apparatus |
US4664655A (en) | 1986-03-20 | 1987-05-12 | Norman Orentreich | High viscosity fluid delivery system |
US4719825A (en) | 1986-03-24 | 1988-01-19 | Lahaye Peter G | Metering needle assembly |
DE3613489A1 (en) | 1986-04-22 | 1987-11-05 | Helmut Vetter | DEVICE FOR HANDLING PRE-FILLED SYRINGES |
DE3773048D1 (en) | 1986-05-15 | 1991-10-24 | Duphar Int Res | AUTOMATIC INJECTION SYRINGE. |
DE3644984A1 (en) | 1986-07-01 | 1988-07-07 | Eberhardt Schlueter | Cartridge or ampoule for an injection device and automatic injection device |
JP2619365B2 (en) | 1986-07-25 | 1997-06-11 | 株式会社日立製作所 | Bloch line memory writing method |
DE3715337C2 (en) | 1986-11-14 | 1994-04-14 | Haselmeier Wilhelm Fa | Injection device |
DE3645245C2 (en) | 1986-11-14 | 1994-01-27 | Haselmeier Wilhelm Fa | Injection appliance |
US4722728A (en) | 1987-01-23 | 1988-02-02 | Patents Unlimited, Ltd. | Needleless hypodermic injector |
DE3715340C2 (en) | 1987-05-08 | 1995-10-19 | Haselmeier Wilhelm Fa | Injection device |
DE3715258C2 (en) | 1987-05-08 | 1996-10-31 | Haselmeier Wilhelm Fa | Injection device |
US6056716A (en) | 1987-06-08 | 2000-05-02 | D'antonio Consultants International Inc. | Hypodermic fluid dispenser |
US5080648A (en) | 1987-06-08 | 1992-01-14 | Antonio Nicholas F D | Hypodermic fluid dispenser |
US5569190A (en) | 1987-06-08 | 1996-10-29 | D'antonio; Nicholas F. | Hypodermic fluid dispenser |
GB8713810D0 (en) | 1987-06-12 | 1987-07-15 | Hypoguard Uk Ltd | Measured dose dispensing device |
US4940460A (en) | 1987-06-19 | 1990-07-10 | Bioject, Inc. | Patient-fillable and non-invasive hypodermic injection device assembly |
US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
US4976701A (en) | 1987-09-25 | 1990-12-11 | Nordisk Gentofte A/S | Injection apparatus |
WO1989006989A1 (en) | 1988-01-29 | 1989-08-10 | The Regents Of The University Of California | Iontophoretic non-invasive sampling or delivery device |
US4973318A (en) | 1988-02-10 | 1990-11-27 | D.C.P. Af 1988 A/S | Disposable syringe |
EP0328699B1 (en) | 1988-02-16 | 1991-09-18 | Arzneimittel GmbH Apotheker Vetter & Co. Ravensburg | Syringe for medical use |
US4830217A (en) | 1988-02-19 | 1989-05-16 | Becton, Dickinson And Company | Body fluid sample collection tube assembly |
US4913699A (en) | 1988-03-14 | 1990-04-03 | Parsons James S | Disposable needleless injection system |
GB8809115D0 (en) | 1988-04-18 | 1988-05-18 | Turner R C | Syringes |
BR8801952A (en) | 1988-04-22 | 1989-11-14 | Sergio Landau | DISPOSABLE CAPSULE, NOT RE-USABLE, CONTAINING INDIVIDUAL DOSE OF VACCINE TO BE HYPODERMICALLY INJECTED, WITHOUT NEEDLE, WITH PRESSURE INJECTOR |
GB8819977D0 (en) | 1988-08-23 | 1988-09-21 | Medimech Ltd | Automatic injectors |
US4929238A (en) | 1988-11-23 | 1990-05-29 | Coeur Laboratories, Inc. | Multi-pressure injector device |
IT1227658B (en) | 1988-12-01 | 1991-04-23 | Vittorio Boschetti B | DISPOSABLE SYRINGE WITH RETURN AND NEEDLE LOCK AT THE END OF INJECTION FOR THE PURPOSE OF AVOID RE-USE |
GB8900763D0 (en) | 1989-01-13 | 1989-03-08 | Kabi Vitrum Peptide Hormones A | Multi-dose syringe |
US4986816A (en) | 1989-01-18 | 1991-01-22 | On-Gard Systems, Inc. | Needle unsheathing, resheathing and handling apparatus |
US4915701A (en) | 1989-02-21 | 1990-04-10 | Halkyard Douglas R | Protective device and syringe |
DE3916101A1 (en) | 1989-05-17 | 1990-11-22 | Vetter & Co Apotheker | SYRINGE FOR MEDICAL PURPOSES |
US5226895A (en) | 1989-06-05 | 1993-07-13 | Eli Lilly And Company | Multiple dose injection pen |
US5569236A (en) | 1989-06-16 | 1996-10-29 | Science Incorporated | Fluid delivery apparatus |
US5102393A (en) | 1989-07-17 | 1992-04-07 | Survival Technology, Inc. | Autoinjector converted from intramuscular to subcutaneous mode of injection |
US5085641A (en) | 1989-07-17 | 1992-02-04 | Survival Technology, Inc. | Conveniently carried frequent use auto-injector with improved cap structure |
US5085642A (en) | 1989-07-17 | 1992-02-04 | Survival Technology, Inc. | Conveniently carried frequent use autoinjector |
DE3924830A1 (en) | 1989-07-27 | 1991-02-07 | Vetter & Co Apotheker | SYRINGE CYLINDER FOR MEDICAL PURPOSES |
US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
GB8926825D0 (en) | 1989-11-28 | 1990-01-17 | Glaxo Group Ltd | Device |
DE59001705D1 (en) | 1990-02-07 | 1993-07-15 | Vetter & Co Apotheker | DOUBLE CHAMBER SYRINGE AND METHOD OF USE. |
US4982769A (en) | 1990-02-21 | 1991-01-08 | Survival Technology, Inc. | Package |
US5050400A (en) | 1990-02-26 | 1991-09-24 | Bohn, Inc. | Simplified hot gas defrost refrigeration system |
KR100192854B1 (en) | 1990-02-28 | 1999-06-15 | 도널드 엘. 앤드루소 | Method for spectral estimation to improve noise robustness for speech recognition |
GB9007113D0 (en) | 1990-03-29 | 1990-05-30 | Sams Bernard | Dispensing device |
US5062830A (en) | 1990-04-04 | 1991-11-05 | Derata Corporation | Dry disposable nozzle assembly for medical jet injector |
DE4021836C1 (en) | 1990-07-09 | 1991-05-02 | Arzneimittel Gmbh Apotheker Vetter & Co Ravensburg, 7980 Ravensburg, De | |
US5505694A (en) | 1990-08-22 | 1996-04-09 | Tcnl Technologies, Inc. | Apparatus and method for raising a skin wheal |
DK228290D0 (en) | 1990-09-21 | 1990-09-21 | Novo Nordisk As | AND INJECTION UNIT |
US5350367A (en) | 1990-11-06 | 1994-09-27 | Sterling Winthrop Inc. | Snap together hypodermic syringe holder |
WO1992008504A1 (en) | 1990-11-17 | 1992-05-29 | Santen Seiyaku Kabushiki Kaisha | Double-chamber type syringe barrel |
US5137528A (en) | 1990-11-26 | 1992-08-11 | Crose Virginia W | Ampoule for administering a liquid local anaesthetic |
GB9100819D0 (en) | 1991-01-15 | 1991-02-27 | Medimech Int Ltd | Subcutaneous injector |
JPH0566177A (en) | 1991-04-22 | 1993-03-19 | Nippon Semiconductor Kk | Air flow visualizer |
US5451210A (en) | 1991-04-29 | 1995-09-19 | Lifequest Medical, Inc. | System and method for rapid vascular drug delivery |
US5405362A (en) | 1991-04-29 | 1995-04-11 | The Board Of Regents For The University Of Texas System | Interactive external defibrillation and drug injection system |
US5271744A (en) | 1991-04-29 | 1993-12-21 | George C. Kramer | System and method for rapid vascular drug delivery |
US5176643A (en) | 1991-04-29 | 1993-01-05 | George C. Kramer | System and method for rapid vascular drug delivery |
US5868711A (en) | 1991-04-29 | 1999-02-09 | Board Of Regents, The University Of Texas System | Implantable intraosseous device for rapid vascular access |
GB9111049D0 (en) | 1991-05-22 | 1991-07-17 | Parkin Adrian | Hypodermic needle |
GB9111600D0 (en) | 1991-05-30 | 1991-07-24 | Owen Mumford Ltd | Improvements relating to injection devices |
EP0518416A1 (en) | 1991-06-13 | 1992-12-16 | Duphar International Research B.V | Injection device |
US5163907A (en) | 1991-06-24 | 1992-11-17 | Szuszkiewicz Christine M | Single use retractable needle syringe |
JPH0516490A (en) | 1991-07-12 | 1993-01-26 | Canon Inc | Information processing equipment |
US5102388A (en) | 1991-07-15 | 1992-04-07 | Richmond John E | Sequential delivery syringe |
JPH0526411A (en) | 1991-07-15 | 1993-02-02 | Gastar Corp | Combustion device |
EP0525525B1 (en) | 1991-07-24 | 1995-05-03 | Medico Development Investment Company | Injector |
JPH0533792A (en) | 1991-07-26 | 1993-02-09 | Matsushita Electric Ind Co Ltd | Self-suction type pump |
JPH0539135A (en) | 1991-07-31 | 1993-02-19 | Fuso Tekko Kk | Sheet material take-up device |
IT1252832B (en) | 1991-08-06 | 1995-06-28 | Sicim Spa | DISPOSABLE HEAD FOR INJECTORS FOR SUBCUTANEOUS INJECTIONS WITHOUT NEEDLE |
JPH0544625A (en) | 1991-08-07 | 1993-02-23 | Mitsubishi Electric Corp | Variable pumping-up storage electric power generating device |
DE4127650C1 (en) | 1991-08-21 | 1993-02-25 | Arzneimittel Gmbh Apotheker Vetter & Co Ravensburg, 7980 Ravensburg, De | |
US5195983A (en) | 1991-08-27 | 1993-03-23 | Penta Associates | Syringe guard and disposal system |
US5544234A (en) | 1991-09-04 | 1996-08-06 | Canon Kabushiki Kaisha | Facsimile apparatus with automatic answering telephone function, and communication method in said apparatus |
JPH0574397A (en) | 1991-09-12 | 1993-03-26 | Hitachi Ltd | Sample fine adjustment device for electron microscope |
US5232540A (en) | 1991-09-30 | 1993-08-03 | Ithaca Industries, Inc. | Automatic labeling machine and method |
US5221348A (en) | 1991-11-26 | 1993-06-22 | Masano Thomas C | High pressure glue injector |
US5263934A (en) | 1991-11-28 | 1993-11-23 | Haak Abraham Van Den | Stroke limiting syringe with retractable needle |
US5332399A (en) | 1991-12-20 | 1994-07-26 | Abbott Laboratories | Safety packaging improvements |
GB9200219D0 (en) | 1992-01-07 | 1992-02-26 | Medimech Int Ltd | Automatic injectors |
US5279586A (en) | 1992-02-04 | 1994-01-18 | Becton, Dickinson And Company | Reusable medication delivery pen |
ATE138582T1 (en) | 1992-03-27 | 1996-06-15 | Duphar Int Res | AUTOMATIC SYRINGE |
US5873857A (en) | 1992-04-17 | 1999-02-23 | Science Incorporated | Fluid dispenser with fill adapter |
SE9201246D0 (en) | 1992-04-21 | 1992-04-21 | Kabi Pharmacia Ab | INJECTION CARTRIDGE ARRANGEMENT |
AU665067B2 (en) | 1992-04-30 | 1995-12-14 | Takeda Pharmaceutical Company Limited | Prefilled syringe |
US5281198A (en) | 1992-05-04 | 1994-01-25 | Habley Medical Technology Corporation | Pharmaceutical component-mixing delivery assembly |
US5180370A (en) | 1992-05-18 | 1993-01-19 | Gillespie Elgene R | Safety hypodermic syringe with retractable needle |
US5279576A (en) | 1992-05-26 | 1994-01-18 | George Loo | Medication vial adapter |
US5304128A (en) | 1992-09-22 | 1994-04-19 | Habley Medical Technology Corporation | Gas powered self contained syringe |
US5569189A (en) | 1992-09-28 | 1996-10-29 | Equidyne Systems, Inc. | hypodermic jet injector |
US5334144A (en) | 1992-10-30 | 1994-08-02 | Becton, Dickinson And Company | Single use disposable needleless injector |
GB9223183D0 (en) | 1992-11-05 | 1992-12-16 | Medimech Int Ltd | Improvements related to auto injectors |
JPH08505543A (en) | 1992-11-19 | 1996-06-18 | テブロ ソシエテ アノニム | Disposable automatic injection device for prefilled syringe |
JP3172005B2 (en) | 1992-11-27 | 2001-06-04 | 株式会社大協精工 | Syringe and container |
GB9226423D0 (en) | 1992-12-18 | 1993-02-10 | Sams Bernard | Incrementing mechanisms |
AU685086B2 (en) | 1993-02-02 | 1998-01-15 | Vidamed, Inc. | Transurethral needle ablation device |
AU682670B2 (en) | 1993-02-05 | 1997-10-16 | Becton Dickinson & Company | Syringe needle isolation device |
US5330431A (en) | 1993-03-12 | 1994-07-19 | Glenn Herskowitz | Infusion pump |
DE69427226T2 (en) | 1993-03-24 | 2001-08-30 | Owen Mumford Ltd., Woodstock | DEVICE FOR INJECTION |
US5358489A (en) | 1993-05-27 | 1994-10-25 | Washington Biotech Corporation | Reloadable automatic or manual emergency injection system |
US5695472A (en) | 1993-05-27 | 1997-12-09 | Washington Biotech Corporation | Modular automatic or manual emergency medicine injection system |
US5540664A (en) | 1993-05-27 | 1996-07-30 | Washington Biotech Corporation | Reloadable automatic or manual emergency injection system |
US5415648A (en) | 1993-07-08 | 1995-05-16 | Malay; Manuel R. | Multiple purpose syringe |
DE69426390T2 (en) | 1993-07-31 | 2001-04-12 | Weston Medical Ltd., Stradbroke Eye | NEEDLE-FREE INJECTOR |
US5425715A (en) | 1993-08-05 | 1995-06-20 | Survival Technology, Inc. | Reloadable injector |
US5308341A (en) | 1993-09-28 | 1994-05-03 | Becton, Dickinson And Company | Method of testing the dose accuracy of a medication delivery device |
US5593388A (en) | 1993-11-11 | 1997-01-14 | N.J. Phillips Pty. Limited | Injector with retractable shroud |
US5354286A (en) | 1993-12-07 | 1994-10-11 | Survival Technology, Inc. | Injection device having polyparaxylylene coated container |
US5478316A (en) | 1994-02-02 | 1995-12-26 | Becton, Dickinson And Company | Automatic self-injection device |
US5514107A (en) | 1994-02-10 | 1996-05-07 | Habley Medical Technology Corporation | Safety syringe adapter for cartridge-needle unit |
US5514097A (en) | 1994-02-14 | 1996-05-07 | Genentech, Inc. | Self administered injection pen apparatus and method |
WO1995024176A1 (en) | 1994-03-07 | 1995-09-14 | Bioject, Inc. | Ampule filling device |
FR2718357B1 (en) | 1994-04-06 | 1997-10-03 | Defarges Alain Moreau | Improvements made to a needleless jet injection device. |
GB9408500D0 (en) | 1994-04-28 | 1994-06-22 | Pa Consulting Services | Improvements in or relating to injection devices |
FR2719224B1 (en) | 1994-04-29 | 1996-08-02 | Nycomed Lab Sa | Rapid exchange dilation catheter. |
DE59510817D1 (en) | 1994-05-30 | 2003-12-04 | B D Medico S A R L | injection device |
GB9412301D0 (en) | 1994-06-17 | 1994-08-10 | Safe T Ltd | Hollow-needle drugs etc applicators |
US5827232A (en) | 1994-06-22 | 1998-10-27 | Becton Dickinson And Company | Quick connect medication delivery pen |
US5725508A (en) | 1994-06-22 | 1998-03-10 | Becton Dickinson And Company | Quick connect medication delivery pen |
IE72524B1 (en) | 1994-11-04 | 1997-04-23 | Elan Med Tech | Analyte-controlled liquid delivery device and analyte monitor |
US5637094A (en) | 1994-11-04 | 1997-06-10 | Pos-T-Vac, Inc. | Multiple dosage syringe |
DE4445969C1 (en) | 1994-12-22 | 1996-03-14 | Schott Glaswerke | Syringe cylinder with two compartments for two constituents |
US5599302A (en) | 1995-01-09 | 1997-02-04 | Medi-Ject Corporation | Medical injection system and method, gas spring thereof and launching device using gas spring |
CA2213682C (en) | 1995-03-07 | 2009-10-06 | Eli Lilly And Company | Recyclable medication dispensing device |
GB9506087D0 (en) | 1995-03-24 | 1995-05-10 | Owen Mumford Ltd | Improvements relating to medical injection devices |
US5562625A (en) | 1995-05-02 | 1996-10-08 | Stefancin, Jr.; Ronald J. | Reusasble syringe with a disposable needle sheath |
IT1275428B (en) | 1995-05-16 | 1997-08-07 | Bracco Spa | PROCESS FOR THE PRODUCTION OF PRE-FILLED SYRINGES WITHOUT RESIDUAL GAS BUBBLES |
US5730723A (en) | 1995-10-10 | 1998-03-24 | Visionary Medical Products Corporation, Inc. | Gas pressured needle-less injection device and method |
US6245347B1 (en) | 1995-07-28 | 2001-06-12 | Zars, Inc. | Methods and apparatus for improved administration of pharmaceutically active compounds |
US6756053B2 (en) * | 1995-07-28 | 2004-06-29 | Zars, Inc. | Controlled heat induced rapid delivery of pharmaceuticals from skin depot |
AU1860697A (en) | 1995-09-08 | 1997-07-28 | Visionary Medical Products Corporation | Pen-type injector drive mechanism |
US5688251A (en) | 1995-09-19 | 1997-11-18 | Becton Dickinson And Company | Cartridge loading and priming mechanism for a pen injector |
US5542760A (en) | 1995-09-26 | 1996-08-06 | Becton Dickinson And Company | Syringe filler for mixing insulins |
DE19537163C1 (en) | 1995-10-06 | 1997-01-30 | Vetter & Co Apotheker | Syringe for medical purposes |
US6080130A (en) | 1998-11-14 | 2000-06-27 | Castellano; Thomas P. | Gas power source for a needle-less injector |
US5776103A (en) | 1995-10-11 | 1998-07-07 | Science Incorporated | Fluid delivery device with bolus injection site |
US5658259A (en) | 1995-10-19 | 1997-08-19 | Meridian Medical Technologies, Inc. | Dental cartridge assembly auto-injector with protective needle cover |
US5567160A (en) | 1995-10-26 | 1996-10-22 | Survival Technology, Inc. | Autoinjector training device |
US5858001A (en) | 1995-12-11 | 1999-01-12 | Elan Medical Technologies Limited | Cartridge-based drug delivery device |
US5836911A (en) | 1996-02-01 | 1998-11-17 | Medi-Ject Corporation | Injection device having positioning means |
US5865795A (en) | 1996-02-29 | 1999-02-02 | Medi-Ject Corporation | Safety mechanism for injection devices |
US5860456A (en) | 1996-03-22 | 1999-01-19 | Eli Lilly And Company | Syringe alignment device |
US5801057A (en) | 1996-03-22 | 1998-09-01 | Smart; Wilson H. | Microsampling device and method of construction |
US5769138A (en) | 1996-04-01 | 1998-06-23 | Medi-Ject Corporation | Nozzle and adapter for loading medicament into an injector |
IT1284642B1 (en) | 1996-05-02 | 1998-05-21 | Ermanno Greco | REFINEMENTS FOR AUTOMATIC SYRINGES FOR INJECTION |
GB9612724D0 (en) | 1996-06-18 | 1996-08-21 | Owen Mumford Ltd | Improvements relating to injection devices |
US5843036A (en) | 1996-08-23 | 1998-12-01 | Becton Dickinson And Company | Non-dosing cartridge for an injection device |
US5875976A (en) | 1996-12-24 | 1999-03-02 | Medi-Ject Corporation | Locking mechanism for nozzle assembly |
WO1998031369A1 (en) | 1997-01-16 | 1998-07-23 | Sekisui Chemical Co., Ltd. | External preparations for percutaneous absorption |
GB9701413D0 (en) | 1997-01-24 | 1997-03-12 | Smithkline Beecham Biolog | Novel device |
EP0994717A4 (en) | 1997-01-24 | 2000-07-26 | Autoimmune Inc | Treatment of autoimmune disease using tolerization in combination with methotrexate |
US5851197A (en) | 1997-02-05 | 1998-12-22 | Minimed Inc. | Injector for a subcutaneous infusion set |
US6607509B2 (en) | 1997-12-31 | 2003-08-19 | Medtronic Minimed, Inc. | Insertion device for an insertion set and method of using the same |
BR9700930A (en) | 1997-02-07 | 1998-12-08 | Rhone Poulenc Rorer Gmbh | Unit for sale intended for parenteral application a device for the execution of parenteral application as well as a refill unit for the above mentioned unit for sale |
US5931151A (en) | 1997-06-07 | 1999-08-03 | Atwood Industries, Inc. | Range for a recreational vehicle with notched control panel |
EP0996477B1 (en) | 1997-07-14 | 2004-01-14 | Novo Nordisk A/S | Injection member |
GB9714948D0 (en) | 1997-07-16 | 1997-09-17 | Owen Mumford Ltd | Improvements relating to injection devices |
US6171276B1 (en) | 1997-08-06 | 2001-01-09 | Pharmacia & Upjohn Ab | Automated delivery device and method for its operation |
US5921966A (en) | 1997-08-11 | 1999-07-13 | Becton Dickinson And Company | Medication delivery pen having an improved clutch assembly |
ES2210799T3 (en) | 1997-08-21 | 2004-07-01 | Ares Trading S.A. | INJECTION DEVICE. |
IE970782A1 (en) | 1997-10-22 | 1999-05-05 | Elan Corp | An improved automatic syringe |
US6045534A (en) | 1997-10-27 | 2000-04-04 | Sarcos, Inc. | Disposable fluid injection module |
FR2770404B1 (en) | 1997-11-05 | 2000-01-28 | Sedat | AUTOMATIC INJECTOR WITH NEEDLE RETRACTION AT THE END OF INJECTION |
DE19751219A1 (en) | 1997-11-19 | 1999-05-27 | Vetter & Co Apotheker | Syringe, especially prefilled syringe, or carpule |
US6203529B1 (en) | 1997-11-19 | 2001-03-20 | B D Medico | Needle arrangement |
US6706000B2 (en) | 1997-11-21 | 2004-03-16 | Amira Medical | Methods and apparatus for expressing body fluid from an incision |
EP1039942B1 (en) | 1997-12-16 | 2004-10-13 | Meridian Medical Technologies, Inc. | Automatic injector for administrating a medicament |
DE29801168U1 (en) | 1998-01-24 | 1999-08-12 | Medico Dev Investment Co | Injection device |
IL135255A0 (en) | 1998-01-30 | 2001-05-20 | Novo Nordisk As | An injection syringe |
GB9803084D0 (en) | 1998-02-14 | 1998-04-08 | Owen Mumford Ltd | Improvements relating to medical injection devices |
US6221053B1 (en) | 1998-02-20 | 2001-04-24 | Becton, Dickinson And Company | Multi-featured medication delivery pen |
US5935949A (en) | 1998-03-20 | 1999-08-10 | Trustees Of Dartmouth College | Use of androgen therapy in fibromyalgia and chronic fatigue syndrome |
GB9808408D0 (en) | 1998-04-18 | 1998-06-17 | Owen Mumford Ltd | Improvements relating to injection devices |
DE19822031C2 (en) | 1998-05-15 | 2000-03-23 | Disetronic Licensing Ag | Auto injection device |
AU768307B2 (en) | 1998-06-05 | 2003-12-04 | Supergen, Inc. | Compositions comprising methotrexate and pentostatin for treating rheumatoid arthritis |
JP2002518514A (en) * | 1998-06-19 | 2002-06-25 | アクゾ・ノベル・エヌ・ベー | Testosterone derivative |
KR100622160B1 (en) | 1998-07-27 | 2006-09-07 | 안타레스 팔마, 인코퍼레이티드 | Injection-assisting probe for medical injector assembly |
JP2002521147A (en) | 1998-07-27 | 2002-07-16 | メディ−ジェクト コーポレイション | Loading mechanism for use in medical syringe assemblies |
US6428528B2 (en) | 1998-08-11 | 2002-08-06 | Antares Pharma, Inc. | Needle assisted jet injector |
SE9803662D0 (en) | 1998-10-26 | 1998-10-26 | Pharmacia & Upjohn Ab | autoinjector |
US6264629B1 (en) | 1998-11-18 | 2001-07-24 | Bioject, Inc. | Single-use needle-less hypodermic jet injection apparatus and method |
US6132395A (en) | 1998-12-08 | 2000-10-17 | Bioject, Inc. | Needleless syringe with prefilled cartridge |
US6383168B1 (en) | 1998-12-08 | 2002-05-07 | Bioject Medical Technologies Inc. | Needleless syringe with prefilled cartridge |
US6083201A (en) | 1999-01-07 | 2000-07-04 | Mckinley Medical, Llp | Multi-dose infusion pump |
DE29900482U1 (en) | 1999-01-14 | 2000-08-31 | Medico Development Investment Co., Ascona | Injection device |
US6695830B2 (en) | 1999-01-15 | 2004-02-24 | Scimed Life Systems, Inc. | Method for delivering medication into an arterial wall for prevention of restenosis |
GB9903475D0 (en) | 1999-02-17 | 1999-04-07 | Owen Mumford Ltd | Improvements relating to injection devices |
EP1033143B1 (en) | 1999-02-26 | 2007-01-10 | F. Hoffmann-La Roche Ag | Device for administering a medication |
SE9901366D0 (en) | 1999-04-16 | 1999-04-16 | Pharmacia & Upjohn Ab | Injector device and method for its operation |
KR100335050B1 (en) | 1999-07-06 | 2002-05-02 | 구자홍 | multiple micro wave oven |
DE19935681A1 (en) | 1999-07-29 | 2001-02-15 | Vetter & Co Apotheker | Device for filling a syringe barrel and / or for placing a stopper in the syringe barrel |
ES2258469T3 (en) | 1999-08-05 | 2006-09-01 | Becton Dickinson And Company | MEDICATION ADMINISTRATION PENCIL. |
US6319224B1 (en) * | 1999-08-20 | 2001-11-20 | Bioject Medical Technologies Inc. | Intradermal injection system for injecting DNA-based injectables into humans |
US6569123B2 (en) | 1999-10-14 | 2003-05-27 | Becton, Dickinson And Company | Prefillable intradermal injector |
US6569143B2 (en) | 1999-10-14 | 2003-05-27 | Becton, Dickinson And Company | Method of intradermally injecting substances |
US6494865B1 (en) | 1999-10-14 | 2002-12-17 | Becton Dickinson And Company | Intradermal delivery device including a needle assembly |
US8465468B1 (en) | 2000-06-29 | 2013-06-18 | Becton, Dickinson And Company | Intradermal delivery of substances |
US6673035B1 (en) | 1999-10-22 | 2004-01-06 | Antares Pharma, Inc. | Medical injector and medicament loading system for use therewith |
CN1236826C (en) * | 1999-10-22 | 2006-01-18 | 安塔雷斯制药公司 | Medical injector and medicament loading system for use therewith |
US6391003B1 (en) | 1999-10-25 | 2002-05-21 | Antares Pharma, Inc. | Locking mechanism for a jet injector |
DE60015805T2 (en) | 2000-01-27 | 2005-11-17 | Biomd Ltd., Perth | DISPOSABLE SYRINGE |
EP1263387B1 (en) | 2000-02-16 | 2004-09-15 | Haselmeier Sàrl | Method for reconstituting an injection liquid and an injection appliance for carrying out such a method |
GB0003790D0 (en) | 2000-02-18 | 2000-04-05 | Astrazeneca Uk Ltd | Medical device |
US6689092B2 (en) | 2000-03-03 | 2004-02-10 | Boehringer International Gmbh | Needle-less injector of miniature type |
WO2001070309A1 (en) | 2000-03-23 | 2001-09-27 | Antares Pharma, Inc. | Single use disposable jet injector |
GB0007071D0 (en) | 2000-03-24 | 2000-05-17 | Sams Bernard | One-way clutch mechanisms and injector devices |
US6607508B2 (en) | 2000-04-27 | 2003-08-19 | Invivotech, Inc. | Vial injector device |
US6613025B1 (en) | 2000-05-25 | 2003-09-02 | Scimed Life Systems, Inc. | Method and apparatus for diagnostic and therapeutic agent delivery |
US6547764B2 (en) | 2000-05-31 | 2003-04-15 | Novo Nordisk A/S | Double pointed injection needle |
US6406456B1 (en) | 2000-06-08 | 2002-06-18 | Avant Drug Delivery Systems, Inc. | Jet injector |
US6517517B1 (en) | 2000-06-08 | 2003-02-11 | Mayo Foundation For Medical Education And Research | Automated injection device for administration of liquid medicament |
WO2001095960A1 (en) | 2000-06-15 | 2001-12-20 | Hambley Limited | Hypodermic syringe with passive aspiration feature |
US6663602B2 (en) | 2000-06-16 | 2003-12-16 | Novo Nordisk A/S | Injection device |
US6530904B1 (en) | 2000-08-15 | 2003-03-11 | Evan T. Edwards | Medical injector |
AU9258101A (en) | 2000-10-09 | 2002-04-22 | Lilly Co Eli | Pen device for administration of parathyroid hormone |
US6656150B2 (en) | 2000-10-10 | 2003-12-02 | Meridian Medical Technologies, Inc. | Wet/dry automatic injector assembly |
US7621887B2 (en) | 2000-10-10 | 2009-11-24 | Meridian Medical Technologies, Inc. | Wet/dry automatic injector assembly |
US6641561B1 (en) | 2000-10-10 | 2003-11-04 | Meridian Medical Technologies, Inc. | Drug delivery device |
FR2815543B1 (en) | 2000-10-19 | 2003-10-24 | Sedat | SELF-INJECTION SYRINGE OF AN EXTEMPORANEOUS MIXTURE |
SE518981C2 (en) | 2000-12-14 | 2002-12-17 | Shl Medical Ab | autoinjector |
US6387078B1 (en) | 2000-12-21 | 2002-05-14 | Gillespie, Iii Richard D. | Automatic mixing and injecting apparatus |
IL156245A0 (en) | 2000-12-22 | 2004-01-04 | Dca Design Int Ltd | Drive mechanism for an injection device |
DE10106367B4 (en) | 2001-02-12 | 2009-11-19 | Tecpharma Licensing Ag | A reading aid for a device for administering an adjustable dose of an injectable product |
US6645170B2 (en) | 2001-03-05 | 2003-11-11 | Bioject Medical Technologies, Inc. | Simplified disposable needle-free injection apparatus and method |
US6471669B2 (en) | 2001-03-05 | 2002-10-29 | Bioject Medical Technologies Inc. | Disposable needle-free injection apparatus and method |
JP2002264621A (en) | 2001-03-12 | 2002-09-18 | Pacific Ind Co Ltd | Transmitter of tire condition monitoring device |
GB0107604D0 (en) | 2001-03-27 | 2001-05-16 | Dca Design Int Ltd | Improvements in and relating to injection device |
GB0107608D0 (en) | 2001-03-27 | 2001-05-16 | Dca Design Int Ltd | Improvements in and relating to an injection device |
CN1520320A (en) | 2001-04-13 | 2004-08-11 | 贝克顿迪肯森公司 | Method of intradermally injecting substances |
GB0110053D0 (en) | 2001-04-24 | 2001-06-13 | Axis Shield Asa | Assay |
WO2002089805A2 (en) | 2001-05-03 | 2002-11-14 | Midamerica Neuroscience Research Foundation | Use of regularly scheduled high dose intravenous methotrexate therapy |
EP2258424B1 (en) | 2001-05-16 | 2013-01-30 | Eli Lilly and Company | Medication injector apparatus |
US6585685B2 (en) | 2001-06-08 | 2003-07-01 | Bioject Inc. | Jet injector apparatus and method |
US7041068B2 (en) | 2001-06-12 | 2006-05-09 | Pelikan Technologies, Inc. | Sampling module device and method |
DE10129585A1 (en) | 2001-06-20 | 2003-01-09 | Disetronic Licensing Ag | Device for the dosed administration of an injectable product |
EP1495777A3 (en) | 2001-07-16 | 2007-01-03 | Eli Lilly And Company | Medication dispensing apparatus configured for rotate to prime and pull/push to inject functionality |
US7544188B2 (en) | 2001-07-19 | 2009-06-09 | Intelliject, Inc. | Medical injector |
GB0118419D0 (en) | 2001-07-28 | 2001-09-19 | Owen Mumford Ltd | Improvements relating to injection devices |
CN1543365A (en) | 2001-08-17 | 2004-11-03 | ������˹ҩƷ��˾ | Administration of insulin by jet injection |
EP1423079B1 (en) | 2001-08-27 | 2006-07-19 | Novo Nordisk A/S | A cartridge and a medical delivery system accommodating such a cartridge |
US6872193B2 (en) | 2001-10-26 | 2005-03-29 | Retractable Technologies, Inc. | IV catheter introducer with retractable needle |
EP1307012A3 (en) | 2001-10-26 | 2009-12-30 | Tenovis GmbH & Co. KG | Telecommunication system and method of control of circuit and packet switching |
US7708719B2 (en) | 2001-11-02 | 2010-05-04 | Meridian Medical Technologies, Inc. | Medicament container, a medicament dispensing kit for administering medication and a method for packaging the same |
US7569035B1 (en) | 2001-11-02 | 2009-08-04 | Meridian Medical Technologies, Inc. | Automatic injector with anti-coring needle |
ATE350086T1 (en) | 2001-11-09 | 2007-01-15 | Alza Corp | COLLAPSIBLE SYRINGE CONTAINER |
PT2221076E (en) | 2001-11-09 | 2013-07-15 | Alza Corp | Pneumatic powered autoinjector |
US7488313B2 (en) | 2001-11-29 | 2009-02-10 | Boston Scientific Scimed, Inc. | Mechanical apparatus and method for dilating and delivering a therapeutic agent to a site of treatment |
US20030105430A1 (en) | 2001-11-30 | 2003-06-05 | Elan Pharma International Limited Wil House | Automatic injector |
GB0129171D0 (en) | 2001-12-06 | 2002-01-23 | Dca Design Int Ltd | Improvements in and relating to a medicament cartridge |
GB0130139D0 (en) | 2001-12-18 | 2002-02-06 | Dca Design Int Ltd | Improvements in and relating to a medicament injection apparatus |
US7247149B2 (en) | 2001-12-20 | 2007-07-24 | Advanced Cardiovascular Systems, Inc. | Contact and penetration depth sensor for a needle assembly |
GB0200637D0 (en) | 2002-01-12 | 2002-02-27 | Dca Design Int Ltd | Improvements in and relating to medicament injection apparatus |
EA013399B1 (en) | 2002-02-07 | 2010-04-30 | Юниверсити Оф Теннесси Рисерч Фаундейшн | Treating benign prostate hyperplasia with a selective androgen receptor modulator (sarm) |
CA2475573C (en) | 2002-02-11 | 2013-03-26 | Antares Pharma, Inc. | Intradermal injector |
GB0203276D0 (en) | 2002-02-12 | 2002-03-27 | Novartis Ag | Organic compounds |
EP1476211B1 (en) | 2002-02-15 | 2015-06-24 | Antares Pharma, Inc. | Injector with bypass channel |
GB0205066D0 (en) | 2002-03-05 | 2002-04-17 | Owen Mumford Ltd | Improvements relating to injection devices |
GB0205485D0 (en) | 2002-03-08 | 2002-04-24 | Dca Design Int Ltd | Improvements in and relating to a medicament delivery service |
JP4350525B2 (en) | 2002-03-18 | 2009-10-21 | イーライ リリー アンド カンパニー | Drug dispensing device with gear set giving mechanical advantages |
US7218962B2 (en) | 2002-03-29 | 2007-05-15 | Boston Scientific Scimed, Inc. | Magnetically enhanced injection catheter |
US6584910B1 (en) | 2002-04-19 | 2003-07-01 | David J. Plass | Animal syringe system |
MY139721A (en) * | 2002-04-19 | 2009-10-30 | Cpex Pharmaceuticals Inc | Pharmaceutical composition |
US7519418B2 (en) | 2002-04-30 | 2009-04-14 | Boston Scientific Scimed, Inc. | Mechanical apparatus and method for dilating and delivering a therapeutic agent to a site of treatment |
BR0311443A (en) | 2002-05-06 | 2005-03-22 | Becton Dickinson Co | Method and device for controlling drug pharmacokinetics |
GB0210631D0 (en) | 2002-05-09 | 2002-06-19 | Glaxo Group Ltd | Novel device |
AU2003241481B2 (en) | 2002-05-16 | 2008-09-04 | Scott Laboratories, Inc. | Drug container entry mechanisms and method |
GB0211294D0 (en) | 2002-05-17 | 2002-06-26 | Owen Mumford Ltd | Improvements relating to injection devices |
US6979316B1 (en) | 2002-05-23 | 2005-12-27 | Seedlings Life Science Ventures Llc | Apparatus and method for rapid auto-injection of medication |
TW200404552A (en) * | 2002-05-30 | 2004-04-01 | Akzo Nobel Nv | Self administered contraception |
EP2286857A1 (en) | 2002-07-02 | 2011-02-23 | Panasonic Corporation | Automatic administration instrument for medical use |
GB2421689B (en) | 2002-08-05 | 2007-03-07 | Caretek Medical Ltd | Drug delivery system |
US20040191225A1 (en) * | 2002-08-06 | 2004-09-30 | Dinsmore Jonathan H. | Injection system |
US20040039337A1 (en) | 2002-08-21 | 2004-02-26 | Letzing Michael Alexander | Portable safety auto-injector |
AU2003278798A1 (en) | 2002-09-12 | 2004-04-30 | Children's Hospital Medical Center | Method and device for painless injection of medication |
DK1542744T3 (en) | 2002-09-24 | 2009-09-28 | Shl Group Ab | injection device |
JP4741234B2 (en) | 2002-10-01 | 2011-08-03 | ベクトン・ディキンソン・アンド・カンパニー | Drug administration pen |
US20040087564A1 (en) * | 2002-10-31 | 2004-05-06 | Wright D. Craig | Delivery composition and method |
JP2006504482A (en) | 2002-11-01 | 2006-02-09 | アンタレス・ファーマ・インコーポレーテッド | Insulin medication by injection injection |
US20040143213A1 (en) | 2002-11-12 | 2004-07-22 | Collegium Pharmaceutical, Inc. | Inertial drug delivery system |
AU2002952691A0 (en) | 2002-11-15 | 2002-11-28 | Sunshine Heart Company Pty Ltd | Heart assist device utilising aortic deformation |
JP4339260B2 (en) | 2002-11-25 | 2009-10-07 | テクファーマ・ライセンシング・アクチェンゲゼルシャフト | Injection device with needle protection device |
AU2003275895B2 (en) | 2002-11-25 | 2009-02-05 | Tecpharma Licensing Ag | Auto-injector comprising a resettable releasing safety device |
EP2526996B1 (en) | 2002-12-20 | 2019-09-11 | Xeris Pharmaceuticals, Inc. | Formulation for intracutaneous injection |
US7252651B2 (en) | 2003-01-07 | 2007-08-07 | Becton, Dickinson And Company | Disposable injection device |
US6969372B1 (en) | 2003-01-07 | 2005-11-29 | Halseth Thor R | Automatic retraction Huber needle safety enclosure |
US6767336B1 (en) | 2003-01-09 | 2004-07-27 | Sheldon Kaplan | Automatic injector |
GB0304823D0 (en) | 2003-03-03 | 2003-04-09 | Dca Internat Ltd | Improvements in and relating to a pen-type injector |
EP2210634A1 (en) | 2009-01-22 | 2010-07-28 | Sanofi-Aventis Deutschland GmbH | Drug delivery device dose setting mechanism |
US7390314B2 (en) | 2003-03-05 | 2008-06-24 | Medtronic Minimed, Inc. | Lead screw driven reservoir with integral plunger nut and method of using the same |
JO2505B1 (en) * | 2003-03-14 | 2009-10-05 | باير شيرنغ فارما اكتنجيسيلشافت | method and pharmaceutical compositions for reliable achievements of acceptable serum testosterone levels |
GB0306642D0 (en) | 2003-03-22 | 2003-04-30 | Dca Design Int Ltd | Improvements in and relating to an injector for a medical product |
US6932794B2 (en) | 2003-04-03 | 2005-08-23 | Becton, Dickinson And Company | Medication delivery pen |
GB0308267D0 (en) | 2003-04-10 | 2003-05-14 | Dca Design Int Ltd | Improvements in and relating to a pen-type injector |
US7517342B2 (en) | 2003-04-29 | 2009-04-14 | Boston Scientific Scimed, Inc. | Polymer coated device for electrically medicated drug delivery |
US6805686B1 (en) | 2003-05-06 | 2004-10-19 | Abbott Laboratories | Autoinjector with extendable needle protector shroud |
GB0312852D0 (en) | 2003-06-05 | 2003-07-09 | Owen Mumford Ltd | Improvements relating to syringe firing mechanisms |
US20070100288A1 (en) | 2003-06-05 | 2007-05-03 | University Of Florida Research Foundation, Inc. | Auto-injection devices and methods for intramuscular administration of medications |
US8308232B2 (en) | 2003-06-10 | 2012-11-13 | Antonio Zamperla S.P.A. | Seat for amusement apparatus |
GB0315600D0 (en) | 2003-07-04 | 2003-08-13 | Owen Mumford Ltd | Improvements relating to automatic injection devices |
DE10330986B4 (en) | 2003-07-09 | 2010-01-07 | Tecpharma Licensing Ag | Non-contact scanning with magnetoresistive sensor |
US7500963B2 (en) | 2003-07-22 | 2009-03-10 | Safety Syringes, Inc. | Systems and methods for automatic medical injection with safeguard |
WO2005011705A1 (en) * | 2003-07-25 | 2005-02-10 | Adams Kenneth W | Enhancement of erectile function |
US20050027255A1 (en) | 2003-07-31 | 2005-02-03 | Sid Technologies, Llc | Automatic injector |
DE20311996U1 (en) | 2003-08-01 | 2003-10-16 | Hoelzle Dieter Tech Projekte | injection device |
CN100531813C (en) | 2003-08-12 | 2009-08-26 | 伊莱利利公司 | Medication dispensing apparatus with triple screw threads for mechanical advantage |
AT7347U1 (en) | 2003-08-29 | 2005-02-25 | Pharma Consult Ges M B H & Co | DEVICE FOR THE AUTOMATIC INJECTION OF INJECTION LIQUIDS |
DE10342059B4 (en) | 2003-09-11 | 2007-03-01 | Tecpharma Licensing Ag | Delivery device with piercing and Ausschutinrichtung |
DE10342058B4 (en) | 2003-09-11 | 2007-10-25 | Tecpharma Licensing Ag | Administration device for an injectable product with a trigger safety device |
IL157981A (en) | 2003-09-17 | 2014-01-30 | Elcam Medical Agricultural Cooperative Ass Ltd | Auto-injector |
US7615030B2 (en) | 2003-10-06 | 2009-11-10 | Active O, Llc | Apparatus and method for administering a therapeutic agent into tissue |
US8066659B2 (en) | 2004-06-15 | 2011-11-29 | Ceramatec, Inc. | Apparatus and method for treating and dispensing a material into tissue |
US8777889B2 (en) | 2004-06-15 | 2014-07-15 | Ceramatec, Inc. | Apparatus and method for administering a therapeutic agent into tissue |
MXPA06004155A (en) | 2003-10-16 | 2006-06-28 | Lilly Co Eli | Fixed dose medication dispensing device. |
US8360114B2 (en) | 2003-10-23 | 2013-01-29 | Niles Clark | Apparatus and method for filing a syringe |
DE20317377U1 (en) | 2003-11-03 | 2005-03-17 | B D Medico S A R L | injection device |
US7635348B2 (en) | 2003-11-04 | 2009-12-22 | Meridian Medical Technologies, Inc. | Container for medicament automatic injector and automatic injector adapted therefor |
US20050101919A1 (en) | 2003-11-07 | 2005-05-12 | Lennart Brunnberg | Device for an injector |
EP1541185A1 (en) | 2003-12-08 | 2005-06-15 | Novo Nordisk A/S | Automatic syringe with priming mechanism |
DE502004010278D1 (en) | 2003-12-18 | 2009-12-03 | Tecpharma Licensing Ag | RELEASE INJECTION DEVICE |
CH696421A5 (en) | 2003-12-18 | 2007-06-15 | Tecpharma Licensing Ag | Autoinjector with arresting the drug container. |
EP1698329A4 (en) | 2003-12-24 | 2009-10-28 | Ltt Bio Pharma Co Ltd | Drug-containing nanoparticle, process for producing the same and parenterally administered preparation from the nanoparticle |
WO2005063331A1 (en) | 2003-12-26 | 2005-07-14 | Hisamitsu Pharmaceutical Co., Inc. | Activation-in-use ion tophoresis device |
WO2005069831A2 (en) | 2004-01-12 | 2005-08-04 | Iscience Surgical Corporation | Injector for viscous materials |
GB2410188B (en) | 2004-01-23 | 2006-01-25 | Medical House Plc | Injection device |
US7138389B2 (en) * | 2004-02-09 | 2006-11-21 | University Of Washington | Oral androgen therapy using modulators of testosterone bioavailability |
US7896841B2 (en) | 2004-02-17 | 2011-03-01 | Children's Hospital Medical Center | Injection device for administering a vaccine |
WO2005091922A2 (en) | 2004-03-03 | 2005-10-06 | Becton, Dickinson And Company | Methods and devices for improving delivery of a substance to skin |
PL1732629T3 (en) | 2004-03-30 | 2019-10-31 | Lilly Co Eli | Medication dispensing apparatus with spring-driven locking feature enabled by administration of final dose |
ES2369671T3 (en) | 2004-03-30 | 2011-12-02 | Eli Lilly & Company | MEDICATION DISPENSING DEVICE WITH A GEAR SET THAT HAS AN OPENING HOUSING OF THE DRIVE ELEMENT. |
DE202004006611U1 (en) | 2004-04-23 | 2005-08-25 | Tecpharma Licensing Ag | Injection device for administering an injectable product with secured dosing device |
GB2414404B (en) | 2004-05-28 | 2009-06-03 | Cilag Ag Int | Injection device |
US20050273054A1 (en) | 2004-06-03 | 2005-12-08 | Florida Atlantic University | Epinephrine auto-injector |
GB0414054D0 (en) | 2004-06-23 | 2004-07-28 | Owen Mumford Ltd | Improvements relating to automatic injection devices |
US7572613B2 (en) | 2004-06-25 | 2009-08-11 | Klein Jeffrey A | Drug delivery system for accelerated subcutaneous absorption |
US7615041B2 (en) | 2004-07-29 | 2009-11-10 | Boston Scientific Scimed, Inc. | Vial adaptor |
US7449012B2 (en) | 2004-08-06 | 2008-11-11 | Meridian Medical Technologies, Inc. | Automatic injector |
US8048035B2 (en) | 2004-08-06 | 2011-11-01 | Meridian Medical Technologies, Inc. | Automatic injector with needle cover |
CN100571627C (en) | 2004-08-16 | 2009-12-23 | 贝克顿·迪金森公司 | Flashback blood collection needle |
EP1796613A4 (en) | 2004-09-08 | 2008-10-01 | Dermatrends Inc | Transdermal delivery of hydrophobic bioactive agents |
AU2005287590B2 (en) | 2004-09-24 | 2011-06-09 | Sanofi-Aventis Deutschland Gmbh | Cap for drug delivery devices |
EP1642607A1 (en) | 2004-10-04 | 2006-04-05 | Sanofi-Aventis Deutschland GmbH | Dose display mechanism for a drug delivery device |
US8313763B2 (en) | 2004-10-04 | 2012-11-20 | Tolmar Therapeutics, Inc. | Sustained delivery formulations of rapamycin compounds |
EP1799287B1 (en) | 2004-10-04 | 2013-06-19 | Sanofi-Aventis Deutschland GmbH | Drive mechanism for a drug delivery device |
CA2584106C (en) | 2004-10-14 | 2011-09-06 | Safety Medical International, Incorporated | Safety medical syringe with retractable needle |
WO2006045529A1 (en) | 2004-10-21 | 2006-05-04 | Novo Nordisk A/S | Injection device with internal dose indicator |
PL1819382T3 (en) | 2004-10-21 | 2010-03-31 | Novo Nordisk As | Injection device with torsion spring and rotatable display |
WO2006055954A2 (en) * | 2004-11-17 | 2006-05-26 | Government Of The U.S.A., As Represented By The Secretary, Department Of Health & Human Services | Steroid formulation and methods of treatment using same |
US7648482B2 (en) | 2004-11-22 | 2010-01-19 | Intelliject, Inc. | Devices, systems, and methods for medicament delivery |
US7947017B2 (en) | 2004-11-22 | 2011-05-24 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
US7648483B2 (en) | 2004-11-22 | 2010-01-19 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
CA2891057C (en) | 2004-11-22 | 2018-11-13 | Kaleo, Inc. | Medicament delivery apparatus and movable indicator |
EP3308813A1 (en) | 2004-11-24 | 2018-04-18 | SHL Group AB | Injection device |
US7297136B2 (en) | 2004-12-06 | 2007-11-20 | Wyrick Ronald E | Medicine injection devices and methods |
US20060129122A1 (en) | 2004-12-06 | 2006-06-15 | Wyrick Ronald E | Method and apparatus for delivering epinephrine |
US7905352B2 (en) | 2004-12-06 | 2011-03-15 | Washington Biotech Corporation | Kits containing medicine injection devices and containers |
US7621891B2 (en) | 2004-12-06 | 2009-11-24 | Washington Biotech Corporation | Method and apparatus for delivering epinephrine |
US7403261B2 (en) | 2004-12-15 | 2008-07-22 | Asml Netherlands B.V. | Lithographic apparatus and device manufacturing method |
DE102004063644A1 (en) | 2004-12-31 | 2006-07-20 | Tecpharma Licensing Ag | Device for the dosed administration of a fluid product with torsion spring drive |
RU2401133C2 (en) | 2005-01-21 | 2010-10-10 | Ново Нордиск А/С | Automatic injection device with upper unlock mechanism |
PT1850892T (en) | 2005-01-24 | 2019-02-08 | Antares Pharma Inc | Prefilled needle assisted syringe jet injector |
US8206360B2 (en) | 2005-02-01 | 2012-06-26 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
US9022980B2 (en) | 2005-02-01 | 2015-05-05 | Kaleo, Inc. | Medical injector simulation device |
MX2007009152A (en) | 2005-02-01 | 2008-03-06 | Intelliject Llc | Devices, systems, and methods for medicament delivery. |
US7731686B2 (en) | 2005-02-01 | 2010-06-08 | Intelliject, Inc. | Devices, systems and methods for medicament delivery |
US8257318B2 (en) | 2005-02-11 | 2012-09-04 | Novo Nordisk A/S | Injection device having a rotatable scale drum |
DE102005017477A1 (en) | 2005-02-18 | 2006-08-31 | Tecpharma Licensing Ag | Spring in or for an injection device |
DE102005063311A1 (en) | 2005-02-23 | 2006-08-24 | Tecpharma Licensing Ag | Dispensing device for medical, diagnosic/cosmetic product, comprises indicator cylinder, housing, promoters for promoting the product relative to the housing, dosing equipment for adjusting product dose, and coupling elements |
AU2006222060B2 (en) | 2005-03-08 | 2011-09-01 | Takeda Gmbh | Roflumilast for the treatment of diabetes mellitus |
JP4353113B2 (en) | 2005-03-14 | 2009-10-28 | ヤマハ株式会社 | Audio mixer parameter setting device |
US20090123571A1 (en) * | 2005-03-25 | 2009-05-14 | Alan Meehan | Method of treating men with testosterone supplement and 5alpha-reductase inhibitor |
AU2006235453A1 (en) | 2005-04-12 | 2006-10-19 | Laboratories Besins International | Method of treating or preventing bone deterioration or osteoporosis |
US7390319B2 (en) | 2005-04-13 | 2008-06-24 | Steven Friedman | Automatic needle injector having safety triggering mechanism |
CN101163514B (en) | 2005-04-24 | 2012-01-25 | 诺和诺德公司 | Injection device |
CH699723B1 (en) | 2005-04-25 | 2010-04-30 | Tecpharma Licensing Ag | A device for administering a fluid product. |
DE602006019712D1 (en) | 2005-05-10 | 2011-03-03 | Novo Nordisk As | |
DE102005023823B4 (en) | 2005-05-24 | 2022-11-17 | Tecpharma Licensing Ag | Dosing device for an injection device and injection device with such a dosing device |
DE102005023824A1 (en) | 2005-05-24 | 2006-12-07 | Tecpharma Licensing Ag | Dosing device for an injection device |
JP5033792B2 (en) | 2005-05-31 | 2012-09-26 | ノボ・ノルデイスク・エー/エス | Injection device with visual content end indication |
JP5026411B2 (en) | 2005-06-01 | 2012-09-12 | エスエイチエル グループ エービー | Drug delivery device |
EP2364742B1 (en) | 2005-06-01 | 2018-11-14 | SHL Group AB | Device for delivering medicament |
EP1904145A2 (en) | 2005-07-06 | 2008-04-02 | Washington Biotech Corp. | Method and apparatus for delivering epinephrine |
EP1904126B1 (en) | 2005-07-08 | 2011-08-10 | Novo Nordisk A/S | Injection device |
US7955304B2 (en) | 2005-07-15 | 2011-06-07 | Shl Group Ab | Injector |
JP5058998B2 (en) | 2005-07-18 | 2012-10-24 | ウェスト ファーマシューティカル サービシズ インコーポレイテッド | Automatic injection syringe with venting means |
US20070055199A1 (en) | 2005-08-10 | 2007-03-08 | Gilbert Scott J | Drug delivery device for buccal and aural applications and other areas of the body difficult to access |
GB0517699D0 (en) | 2005-09-01 | 2005-10-05 | Owen Mumford Ltd | Needle shroud assembly |
US20070185432A1 (en) | 2005-09-19 | 2007-08-09 | Transport Pharmaceuticals, Inc. | Electrokinetic system and method for delivering methotrexate |
US20110098656A1 (en) | 2005-09-27 | 2011-04-28 | Burnell Rosie L | Auto-injection device with needle protecting cap having outer and inner sleeves |
CN101282752A (en) | 2005-10-11 | 2008-10-08 | 伊莱利利公司 | Apparatus for injecting a pharmaceutical |
US7611502B2 (en) | 2005-10-20 | 2009-11-03 | Covidien Ag | Connector for enteral fluid delivery set |
DE102005052502A1 (en) | 2005-11-03 | 2007-05-16 | Tecpharma Licensing Ag | Auto-injector activation trigger element |
JP5177949B2 (en) | 2005-11-11 | 2013-04-10 | アングルトライ株式会社 | Spectral waveform pattern peak position correction method and program |
GB0524604D0 (en) | 2005-12-02 | 2006-01-11 | Owen Mumford Ltd | Injection method and apparatus |
GB0524962D0 (en) | 2005-12-07 | 2006-01-18 | Pharmakodex Ltd | Topical pharmaceutical compositions |
GB2433032A (en) | 2005-12-08 | 2007-06-13 | Owen Mumford Ltd | Syringe with dose adjustment means |
US7988675B2 (en) | 2005-12-08 | 2011-08-02 | West Pharmaceutical Services Of Delaware, Inc. | Automatic injection and retraction devices for use with pre-filled syringe cartridges |
US7988660B2 (en) | 2005-12-20 | 2011-08-02 | Eli Lilly And Company | Needle-free injection device |
TW200744697A (en) | 2006-02-28 | 2007-12-16 | Verus Pharmaceuticals Inc | Shock absorber for an automatic injector |
EP1996259B1 (en) | 2006-03-10 | 2012-08-15 | Novo Nordisk A/S | An injection device and a method of changing a cartridge in the device |
JP5183499B2 (en) | 2006-03-10 | 2013-04-17 | ノボ・ノルデイスク・エー/エス | Injection device |
US20090069756A1 (en) | 2006-03-20 | 2009-03-12 | Novo Nordisk A/S | Determination of Cartridge Content by Capacitive Means |
EP1999666A1 (en) | 2006-03-20 | 2008-12-10 | Novo Nordisk A/S | Electronic module for mechanical medication delivery devices |
FR2899482A1 (en) | 2006-04-11 | 2007-10-12 | Becton Dickinson France Soc Pa | Automatic medicament/product injection device for patient, has safety shield coupled to housing, and provided in active state at end of needle insertion step before which product/medicament injection step is not started |
DE102006017209A1 (en) | 2006-04-12 | 2007-10-18 | Tecpharma Licensing Ag | Injection device with tension spring and tensioning element |
WO2007118907A1 (en) | 2006-04-19 | 2007-10-25 | Novo Nordisk A/S | A fluid infusion system, a method of assembling such system and drug reservoir for use in the system |
WO2007131025A1 (en) | 2006-05-03 | 2007-11-15 | Antares Pharma, Inc. | Injector with adjustable dosing |
WO2007131013A1 (en) | 2006-05-03 | 2007-11-15 | Antares Pharma, Inc. | Two-stage reconstituting injector |
GB2465919B (en) | 2006-05-10 | 2010-12-08 | Owen Mumford Ltd | Injection device with cap that can be re-fitted post injection |
GB2437924B (en) | 2006-05-11 | 2010-12-22 | Owen Mumford Ltd | Injection device |
US8226618B2 (en) | 2006-05-16 | 2012-07-24 | Novo Nordisk A/S | Gearing mechanism for an injection device |
US9192727B2 (en) | 2006-05-18 | 2015-11-24 | Novo Nordisk A/S | Injection device with mode locking means |
WO2007137930A1 (en) | 2006-05-29 | 2007-12-06 | Novo Nordisk A/S | Mechanism for injection device |
ATE471732T1 (en) | 2006-05-30 | 2010-07-15 | Lilly Co Eli | MODULE FOR A DEVICE FOR INJECTING MEDICINAL PRODUCTS |
US20070293582A1 (en) | 2006-06-05 | 2007-12-20 | Malcolm Hill | Epinephrine dosing regimens comprising buccal, lingual or sublingual and injectable dosage forms |
US8323237B2 (en) | 2006-06-21 | 2012-12-04 | Novo Nordisk Healthcare Ag | One-hand operated drug mixing and expelling device |
CN103316403B (en) | 2006-06-30 | 2017-05-24 | 艾伯维生物技术有限公司 | Automatic injection device |
JP5039135B2 (en) | 2006-07-03 | 2012-10-03 | ノボ・ノルデイスク・エー/エス | Connection for injection device |
ITMO20060222A1 (en) | 2006-07-10 | 2008-01-11 | Alfio Bertolini | ANTIEMORRAGIC MEDICATION PACKAGE |
DE102006033837A1 (en) | 2006-07-21 | 2008-01-31 | Medac Gesellschaft für klinische Spezialpräparate m.b.H | Concentrated methotrexate solutions |
DE102006038101A1 (en) | 2006-08-14 | 2008-02-21 | Tecpharma Licensing Ag | Injection device with jaw safety |
DE102007001432A1 (en) | 2006-08-14 | 2008-02-21 | Tecpharma Licensing Ag | Blocking unit for dosing mechanism of injection device, has retaining unit acting together with dosing mechanism or dosing unit such that adjusting movement of mechanism or dosing unit in starting position of blocking unit is prevented |
CN101511410B (en) | 2006-08-28 | 2013-02-06 | 诺沃-诺迪斯克有限公司 | A medical delivery system adapted to be locked axially and unlocked rotationally |
DE102006042236A1 (en) | 2006-09-06 | 2008-03-27 | Tecpharma Licensing Ag | Needle guard with blocked guard position |
DE102006041809B4 (en) | 2006-09-06 | 2012-11-15 | Tecpharma Licensing Ag | Needle protection device with blocking device |
DE102006042233B3 (en) | 2006-09-06 | 2008-03-06 | Tecpharma Licensing Ag | Needle guard with distal and proximal needle guard |
FR2905273B1 (en) | 2006-09-06 | 2009-04-03 | Becton Dickinson France Soc Pa | AUTOMATIC INJECTION DEVICE WITH TIMING MEANS. |
WO2008031236A1 (en) | 2006-09-15 | 2008-03-20 | Tecpharma Licensing Ag | Splash-resistant injection device |
ES2411732T3 (en) | 2006-09-29 | 2013-07-08 | Novo Nordisk A/S | Injection device with electronic detection means |
US7547293B2 (en) | 2006-10-06 | 2009-06-16 | Bioject, Inc. | Triggering mechanism for needle-free injector |
US7811254B2 (en) | 2006-10-18 | 2010-10-12 | Meridian Medical Technologies, Inc. | Autoinjector with needle depth adapter |
WO2008047372A2 (en) | 2006-10-19 | 2008-04-24 | Elcam Medical Agricultural Cooperative Association Ltd. | Automatic injection device |
EP1923084A1 (en) | 2006-11-17 | 2008-05-21 | Sanofi-Aventis Deutschland GmbH | Dosing and drive mechanism for drug delivery device |
EP1923083A1 (en) | 2006-11-17 | 2008-05-21 | Sanofi-Aventis Deutschland GmbH | Drive mechanisms for use in drug delivery devices |
EP2099384B1 (en) | 2006-11-28 | 2018-09-05 | Roche Diabetes Care GmbH | An insertion device and method for inserting a subcutaneously insertable element into a body |
JP2010512817A (en) | 2006-12-15 | 2010-04-30 | ノボ・ノルデイスク・エー/エス | Medical delivery system comprising a container and a dosing assembly having a radially moving fastening means |
EP2091600B1 (en) | 2006-12-21 | 2019-02-20 | Novo Nordisk A/S | A syringe device |
ZA200904568B (en) * | 2007-01-11 | 2010-09-29 | Acrux Dds Pty Ltd | Spreading implement |
DE602008001779D1 (en) | 2007-01-17 | 2010-08-26 | Shl Group Ab | DEVICE FOR DISPOSING MEDICAMENTS |
DE102007004211A1 (en) | 2007-01-27 | 2008-07-31 | Lts Lohmann Therapie-Systeme Ag | Disposable injector with at least one towing hook |
CA2676810C (en) | 2007-02-05 | 2016-06-21 | Novo Nordisk A/S | Injection button |
WO2008106806A1 (en) | 2007-03-02 | 2008-09-12 | Tecpharma Licensing Ag | Modular administration system |
JP2010519993A (en) | 2007-03-07 | 2010-06-10 | ノボ・ノルデイスク・エー/エス | Drug delivery device with multiple reservoirs |
EP2134393B1 (en) | 2007-03-07 | 2017-09-20 | Novo Nordisk A/S | Back needle |
ES2657483T3 (en) | 2007-03-09 | 2018-03-05 | Eli Lilly And Company | Delay mechanism for an automatic injection device |
KR100820523B1 (en) | 2007-03-14 | 2008-04-08 | 홍관호 | Blood lancet device |
CN101951980A (en) | 2007-03-21 | 2011-01-19 | 米德兰医疗设备控股有限公司 | Safety medical syringe with retractable needle and including a plunger that is received within a barrel |
CN101678167B (en) | 2007-03-22 | 2013-09-18 | 特克法马许可公司 | Spring assembly in an injection device |
EP2125081B1 (en) | 2007-03-23 | 2017-12-20 | Novo Nordisk A/S | An injection device comprising a locking nut |
WO2008116688A1 (en) | 2007-03-23 | 2008-10-02 | Shl Medical Ab | Auto injector |
GB0705782D0 (en) | 2007-03-26 | 2007-05-02 | Novartis Ag | Vial assemblies |
DE102007016811A1 (en) | 2007-04-05 | 2008-10-09 | Tecpharma Licensing Ag | Device for administering a fluid substance from a multi-chamber ampoule |
PL2144649T3 (en) | 2007-04-05 | 2012-01-31 | Tecpharma Licensing Ag | Administering apparatus with functional drive element |
DE102007018868A1 (en) | 2007-04-19 | 2008-10-23 | Lts Lohmann Therapie-Systeme Ag | Disposable injector with at least one towing hook and a sliding wedge gear for unlocking releasing a locking element |
US8057427B2 (en) | 2007-05-09 | 2011-11-15 | Meridian Medical Technologies, Inc. | Drug delivery system with a small amount of a therapeutic agent |
US9878103B2 (en) | 2007-05-14 | 2018-01-30 | Shl Group Ab | Delivery device |
DE102007026083A1 (en) | 2007-05-25 | 2008-11-27 | Haselmeier S.A.R.L. | injection device |
US8273798B2 (en) | 2007-06-04 | 2012-09-25 | Shear Kershman Laboratories | Tamper resistant lipid-based oral dosage form for opioid agonists |
US9179867B2 (en) | 2007-06-19 | 2015-11-10 | Stat Medical Devices, Inc. | Lancet device with depth adjustment and lancet removal system and method |
ATE501752T1 (en) | 2007-06-19 | 2011-04-15 | Shl Group Ab | DEVICE FOR MEDICATION ADMINISTRATION |
DE102007030327A1 (en) | 2007-06-29 | 2009-01-02 | Tecpharma Licensing Ag | Injection device with a spring for a needle protection sleeve |
US9242044B2 (en) | 2007-07-06 | 2016-01-26 | Novo Nordisk A/S | Automatic injection device |
CN101687078B (en) | 2007-07-06 | 2012-07-25 | Shl集团有限责任公司 | One shot injector with dual springs |
GB2452030A (en) | 2007-08-10 | 2009-02-25 | Owen Mumford Ltd | Injection devices |
WO2009040602A1 (en) | 2007-09-25 | 2009-04-02 | Becton Dickinson France | Autoinject0r with deactivating means moveable by a safety shield |
US8491530B2 (en) | 2007-09-25 | 2013-07-23 | Becton Dickinson France | Autoinjector with trigger positionable in active position by movement of a safety shield and indication of the active position |
ES2651624T3 (en) | 2007-09-25 | 2018-01-29 | Becton Dickinson France | Autoinjector received in an external receptacle |
ES2710175T3 (en) | 2007-09-25 | 2019-04-23 | Becton Dickinson France | Auto-injector with deactivation means that can be moved by a safety guard |
DK2211943T3 (en) | 2007-10-10 | 2017-03-06 | Shl Group Ab | GAS SPRING OPERATED MEDICINE ADMINISTRATION DEVICE |
DE202008014334U1 (en) | 2007-10-17 | 2009-02-26 | Haselmeier S.A.R.L. | injection device |
EP2201259B1 (en) | 2007-10-22 | 2013-12-11 | Gkn Sinter Metals, Llc | Reduced stress pawl and ratchet tooth for a one-way clutch |
DE102007053743A1 (en) | 2007-11-12 | 2009-06-10 | Tecpharma Licensing Ag | Rotatable guide sleeve with over-tensioned spring |
US8876779B2 (en) | 2007-11-12 | 2014-11-04 | Bang & Olufsen Medicom A/S | Auto injector with changing anchor locations for a mechanical driver |
CN101983079B (en) | 2007-11-14 | 2014-07-02 | Shl集团有限责任公司 | Automatic injection device with actively triggered syringe withdrawal |
AU2008342558B2 (en) | 2007-12-31 | 2013-11-28 | Novo Nordisk A/S | Electronically monitored injection device |
GB0800103D0 (en) | 2008-01-04 | 2008-02-13 | Owen Mumford Ltd | Sheath removver device |
JP5475689B2 (en) | 2008-01-23 | 2014-04-16 | ノボ・ノルデイスク・エー/エス | Device for injecting a liquid dose of an allotted dose |
CN101998869B (en) | 2008-02-11 | 2013-04-17 | 特克法马许可公司 | Administering apparatus comprising a blockable actuation element |
US8632507B2 (en) | 2008-02-12 | 2014-01-21 | Shl Group Ab | Auto-injector |
DE102008011881A1 (en) | 2008-02-29 | 2009-09-10 | Tecpharma Licensing Ag | Empty shooting speed limit brake |
US8814834B2 (en) | 2008-03-10 | 2014-08-26 | Antares Pharma, Inc. | Injector safety device |
US8177758B2 (en) | 2008-04-08 | 2012-05-15 | Rochester Area Consulting Engineers (RACE) | Pneumatic injector |
GB0806814D0 (en) * | 2008-04-15 | 2008-05-14 | Medical House Plc The | Improved autoinjector |
US8647309B2 (en) | 2008-05-02 | 2014-02-11 | Sanofi-Aventis Deutschland Gmbh | Medication delivery device |
US8267900B2 (en) | 2008-05-02 | 2012-09-18 | Sanofi-Aventis Deutschland Gmbh | Medication delivery device |
GB2460398A (en) | 2008-05-20 | 2009-12-02 | Owen Mumford Ltd | Auto-injector having a magnetic injection indicator and a needle sheath retainer |
WO2009141005A1 (en) | 2008-05-20 | 2009-11-26 | Tecpharma Licensing Ag | Device for administering an injectable product comprising a residual amount display |
US8372031B2 (en) | 2008-06-02 | 2013-02-12 | Shl Group Ab | Medicament delivery device |
AT506690B1 (en) | 2008-06-16 | 2009-11-15 | Pharma Consult Ges M B H & Co | INJECTION DEVICE |
GB2461088B (en) | 2008-06-19 | 2012-09-26 | Cilag Gmbh Int | Injection device |
BRPI0910000B8 (en) | 2008-06-20 | 2021-06-22 | West Pharmaceutical Services Inc | automatic injection mechanism with front support cross reference to related requests |
US9155842B2 (en) | 2008-07-09 | 2015-10-13 | Sanofi-Aventis Deutschland Gmbh | Medication delivery device and method of assembling a medication delivery device |
PL2307079T3 (en) | 2008-07-15 | 2015-12-31 | Shl Group Ab | Medicament delivery device |
EP2313135B1 (en) | 2008-07-17 | 2019-11-06 | Medigard Limited | A retractable syringe |
ES2738539T3 (en) | 2008-08-05 | 2020-01-23 | Antares Pharma Inc | Multi dose injector |
GB2462811B (en) | 2008-08-18 | 2012-08-15 | Medical House Ltd | Improved autoinjector |
DE202008011175U1 (en) | 2008-08-18 | 2010-01-07 | Haselmeier Gmbh | injection device |
GB2463034B (en) | 2008-08-28 | 2012-11-07 | Owen Mumford Ltd | Autoinjection devices |
JP5603335B2 (en) | 2008-08-29 | 2014-10-08 | ノボ・ノルデイスク・エー/エス | Medical syringe with time delay indicator |
WO2010037759A1 (en) | 2008-10-01 | 2010-04-08 | Shl Group Ab | Medicament delivery device powered by volute spring |
SI2346552T2 (en) | 2008-10-13 | 2020-06-30 | Sanofi-Aventis Deutschland Gmbh | Drug delivery device and method of manufacturing a drug delivery device |
US8568434B2 (en) | 2008-10-14 | 2013-10-29 | Bionime Corporation | Lancing device |
JP5558477B2 (en) | 2008-10-24 | 2014-07-23 | ノボ・ノルデイスク・エー/エス | Dial-down mechanism for roll-up pen |
CN102271732B (en) | 2008-11-14 | 2014-12-31 | 得克萨斯大学体系董事会 | Nanochanneled device and related methods |
AU2009326321B2 (en) | 2008-12-12 | 2013-01-17 | Shl Group Ab | Medicament delivery device |
US8366680B2 (en) | 2008-12-12 | 2013-02-05 | Sanofi-Aventis Deutschland Gmbh | Resettable drive mechanism for a medication delivery device and medication delivery device |
DK2355870T3 (en) | 2008-12-12 | 2016-06-06 | Shl Group Ab | Drug delivery devices |
DK2355867T3 (en) | 2008-12-12 | 2014-09-08 | Shl Group Ab | DEVICE FOR MEDICINE DELIVERY |
JP5331895B2 (en) | 2008-12-12 | 2013-10-30 | エス・ホー・エル・グループ・アクチボラゲット | Delivery member mounting device |
DK2376149T3 (en) | 2008-12-12 | 2014-11-24 | Shl Group Ab | Drug delivery device |
DK2355872T3 (en) | 2008-12-12 | 2016-02-22 | Shl Group Ab | Drug delivery device |
GB0823693D0 (en) | 2008-12-31 | 2009-02-04 | Owen Mumford Ltd | Autoinjector |
US7940537B2 (en) | 2008-12-31 | 2011-05-10 | Teco-Westinghouse Motor Company | Partial regeneration in a multi-level power inverter |
EP2208503A1 (en) | 2009-01-20 | 2010-07-21 | Sanofi-Aventis Deutschland GmbH | Drive assembly and medication delivery device |
WO2010084084A1 (en) | 2009-01-23 | 2010-07-29 | Sanofi-Aventis Deutschland Gmbh | Medicament identification system for multi-dose injection devices |
CN102301392B (en) | 2009-01-29 | 2014-08-13 | 日本电气株式会社 | Color image processing method, color image processing device, and recording medium |
WO2010086273A1 (en) | 2009-01-30 | 2010-08-05 | Sanofi-Aventis Deutschland Gmbh | Cartridge and medication delivery device |
AU2010210160B2 (en) | 2009-02-05 | 2014-09-04 | Sanofi-Aventis Deutschland Gmbh | Medicament delivery devices |
RU2524122C2 (en) | 2009-02-05 | 2014-07-27 | Санофи-Авентис Дойчланд Гмбх | Devices for medication introduction |
GB0901801D0 (en) | 2009-02-05 | 2009-03-11 | Medical House Plc The | Improved autoinjector |
WO2010093834A2 (en) | 2009-02-12 | 2010-08-19 | Incube Labs, Llc | Skin penetrating device and method for subcutaneous solid drug delivery |
DK2401010T3 (en) | 2009-02-26 | 2018-07-23 | Shl Group Ab | DOSE ADJUSTMENT MECHANISM |
EP2401009B1 (en) | 2009-02-26 | 2012-11-28 | Tecpharma Licensing AG | Product container holder for an injection device and for receiving a product container |
US8366682B2 (en) | 2009-03-04 | 2013-02-05 | Washington Biotech Corporation | Medicine injection apparatuses |
JP5608686B2 (en) | 2009-03-05 | 2014-10-15 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Drug delivery device with retractable needle |
CA2753982A1 (en) | 2009-03-05 | 2010-09-10 | Sanofi-Aventis Deutschland Gmbh | Needle unit |
US9216255B2 (en) | 2009-03-05 | 2015-12-22 | Sanofi-Aventis Deutschland Gmbh | Needle assembly |
EP2403561B1 (en) | 2009-03-06 | 2017-10-18 | Sanofi-Aventis Deutschland GmbH | Syringe, auto-injector device and set of auto-injector devices and syringes |
EP2405961A4 (en) | 2009-03-09 | 2012-08-08 | Purdue Research Foundation | Compact device for rapidly mixing and delivering substances to a patient |
EP2405962B1 (en) | 2009-03-13 | 2017-12-06 | Eli Lilly and Company | Apparatus for injecting a pharmaceutical with automatic syringe retraction following injection |
WO2010108116A1 (en) | 2009-03-20 | 2010-09-23 | Antares Pharma, Inc. | Hazardous agent injection system |
NZ595343A (en) | 2009-03-30 | 2013-05-31 | Sanofi Aventis Deutschland | A piston rod and a drug delivery device incorporating the piston rod, wherein the piston rod comprises at least two axially aligned guideposts configured to engage a drive member of the drug delivery device |
JP5787874B2 (en) | 2009-03-31 | 2015-09-30 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Medical devices having mechanisms with springs and the use of wave springs or wave washers in medical devices |
DK2414003T3 (en) | 2009-03-31 | 2015-08-24 | Sanofi Aventis Deutschland | Device for pharmaceutical feed |
BRPI1012730A2 (en) | 2009-03-31 | 2016-05-03 | Sanofi Aventis Deutschland | drug delivery device |
CA2756141A1 (en) | 2009-03-31 | 2010-10-07 | Sanofi-Aventis Deutschland Gmbh | Drug delivery device body |
CA2756939A1 (en) | 2009-03-31 | 2010-10-14 | Sanofi-Aventis Deutschland Gmbh | Method for manufacturing a drug delivery device body using an adhesive and drug delivery device body |
US9364613B2 (en) | 2009-03-31 | 2016-06-14 | Sanofi-Aventis Deutschland Gmbh | Mounting arrangement and coupling assembly for a drug-delivery device |
CA2756972A1 (en) | 2009-03-31 | 2010-10-07 | Sanofi-Aventis Deutschland Gmbh | Medical device having a mechanism and use of a low-friction synthetic material within a medical device |
BRPI1010237A2 (en) | 2009-03-31 | 2016-10-18 | Sanofi Aventis Deustschland Gmbh | drug delivery device |
AU2010233924B2 (en) | 2009-04-01 | 2012-09-27 | Shl Group Ab | Medicament delivery device |
WO2010115670A1 (en) | 2009-04-03 | 2010-10-14 | Shl Group Ab | Medicament delivery device |
US8424768B2 (en) | 2009-04-09 | 2013-04-23 | Metrologic Instruments, Inc. | Trigger mechanism for hand held devices |
GB0906640D0 (en) | 2009-04-17 | 2009-06-03 | Owen Mumford Ltd | A needle cap assembly |
GB2469672B (en) | 2009-04-23 | 2013-09-25 | Medical House Ltd | Improved autoinjector |
EP2421587B1 (en) | 2009-04-24 | 2019-05-22 | SHL Medical AG | Medicament delivery device |
CN102458537B (en) | 2009-04-27 | 2014-07-16 | Shl集团有限责任公司 | Safety pen needle device |
TWI583418B (en) | 2009-04-29 | 2017-05-21 | 艾伯維生物技術有限責任公司 | Syringe plunger and automatic injection device |
SG175102A1 (en) | 2009-04-30 | 2011-12-29 | Sanofi Aventis Deutschland | Axially adjustable connection of piston rod to piston for drive mechanism of a drug delivery device |
US9227009B2 (en) | 2009-04-30 | 2016-01-05 | Sanofi-Aventis Deutschland Gmbh | Pen-type injector with ergonomic button arrangement |
GB0907534D0 (en) | 2009-05-01 | 2009-06-10 | Owen Mumford Ltd | Injection devices |
PT2300078E (en) | 2009-05-07 | 2016-06-23 | Medical Injection Devices Inc | Medicament dispensing device |
DK2954914T3 (en) | 2009-05-29 | 2019-03-11 | Tecpharma Licensing Ag | Injection device, especially auto-injector with plug protection and / or overload protection for a product container |
US20110015576A1 (en) | 2009-06-01 | 2011-01-20 | Sanofi-Aventis Deutschland Gmbh | Medicament identification system for multi-dose injection devices |
US8672896B2 (en) | 2009-06-01 | 2014-03-18 | Sanofi-Aventis Deutschland Gmbh | Inner housing for a drug delivery device |
US9108007B2 (en) | 2009-06-01 | 2015-08-18 | Sanofi-Aventis Deutschland Gmbh | Spindle and bearing combination and drug delivery device |
US9463283B2 (en) | 2009-06-01 | 2016-10-11 | Sanofi-Aventis Deutschland Gmbh | Dosing mechanism for a drug deliver device |
US9238106B2 (en) | 2009-06-01 | 2016-01-19 | Sanofi-Aventis Deutschland Gmbh | Dose setting mechanism for priming a drug delivery device |
US10034982B2 (en) | 2009-06-01 | 2018-07-31 | Sanofi-Aventis Deutschland Gmbh | Spindle for a drug delivery device |
US9623187B2 (en) | 2009-06-01 | 2017-04-18 | Sanofi-Aventis Deutschland Gmbh | Resettable drug delivery device |
US8974423B2 (en) | 2009-06-01 | 2015-03-10 | Sanofi-Aventis Deutschland Gmbh | Resettable drug delivery device |
US9125994B2 (en) | 2009-06-01 | 2015-09-08 | Sanofi—Aventis Deutschland GmbH | Drug delivery device with dose dial sleeve rotational stop |
US9345840B2 (en) | 2009-06-01 | 2016-05-24 | Sanofi-Aventis Deutschland Gmbh | Drug delivery dose setting mechanism with variable maximum dose |
US9199040B2 (en) | 2009-06-01 | 2015-12-01 | Sanofi-Aventis Deutschland Gmbh | Drug delivery device last dose lock-out mechanism |
US9950116B2 (en) | 2009-06-01 | 2018-04-24 | Sanofi-Aventis Deutschland Gmbh | Dose setting mechanism for priming a drug delivery device |
US9457150B2 (en) | 2009-06-01 | 2016-10-04 | Sanofi-Aventis Deutschland Gmbh | Biasing mechanism for a drug delivery device |
US8585656B2 (en) | 2009-06-01 | 2013-11-19 | Sanofi-Aventis Deutschland Gmbh | Dose setting mechanism for priming a drug delivery device |
US8728043B2 (en) | 2009-06-01 | 2014-05-20 | Sanofi-Aventis Deutschland Gmbh | Drive mechanism for a drug delivery device |
US8257319B2 (en) | 2009-06-01 | 2012-09-04 | Sanofi-Aventis Deutschland Gmbh | Drug delivery device inner housing having helical spline |
TW201103592A (en) | 2009-06-02 | 2011-02-01 | Sanofi Aventis Deutschland | Medicated module for a drug delivery device |
AR076718A1 (en) | 2009-06-02 | 2011-06-29 | Sanofi Aventis Deutschland | MEDICINAL MODULE WITH USER SELECTION |
TW201109060A (en) | 2009-06-02 | 2011-03-16 | Sanofi Aventis Deutschland | Delivery of two or more medicaments through a single dose selection and dispense interface |
TW201109058A (en) | 2009-06-02 | 2011-03-16 | Sanofi Aventis Deutschland | Medicated module with needle guard |
TW201103594A (en) | 2009-06-02 | 2011-02-01 | Sanofi Aventis Deutschland | Medicated module with premix medicament |
TW201109056A (en) | 2009-06-02 | 2011-03-16 | Sanofi Aventis Deutschland | Delivery of two or more medicaments through a single dose selection and single dispense interface |
WO2010140974A1 (en) | 2009-06-05 | 2010-12-09 | Shl Group Ab | Medicament delivery device |
US20100324480A1 (en) | 2009-06-17 | 2010-12-23 | Thomas Chun | Automatic injection syringe assembly |
WO2010147552A1 (en) | 2009-06-18 | 2010-12-23 | Shl Group Ab | Safety pen needle device |
EP2445551B1 (en) | 2009-06-23 | 2019-09-18 | Tecpharma Licensing AG | Injection device having a dosing mechanism for limiting a dose setting |
GB2471304B (en) | 2009-06-24 | 2013-12-11 | Oval Medical Technologies Ltd | A pre-filled syringe or autoinjector |
DK2445552T3 (en) | 2009-06-24 | 2016-01-25 | Tecpharma Licensing Ag | Administering the init function |
EP2266647A1 (en) | 2009-06-25 | 2010-12-29 | Sanofi-Aventis Deutschland GmbH | Drive mechanism for drug delivery device |
GB2471473A (en) | 2009-06-30 | 2011-01-05 | Owen Mumford Ltd | Syringe sheath remover |
US8263581B2 (en) | 2009-07-03 | 2012-09-11 | Jdp Therapeutics, Inc. | Non-sedating antihistamine injection formulations and methods of use thereof |
TWI393578B (en) | 2009-07-07 | 2013-04-21 | Shl Group Ab | Injection device |
ES2443951T3 (en) | 2009-07-08 | 2014-02-21 | Novo Nordisk A/S | Injection device with freeze protection |
EP2451511B1 (en) | 2009-07-08 | 2019-01-23 | Novo Nordisk A/S | Auto-priming injection device |
GB2471726B (en) | 2009-07-10 | 2013-09-11 | Oval Medical Technologies Ltd | A pre-filled syringe including an oxygen absorber |
US8882709B2 (en) | 2009-07-14 | 2014-11-11 | Sanofi-Aventis Deutschland Gmbh | Injection arrangement |
CA2765631A1 (en) | 2009-07-15 | 2011-01-20 | Sanofi-Aventis Deutschland Gmbh | Drive assembly for a pen-type injector and pen-type injector with a drive assembly |
CN102470208A (en) | 2009-07-15 | 2012-05-23 | 赛诺菲-安万特德国有限公司 | Thrust bearing assembly, drive train, and medicament delivery device |
EP2453955B1 (en) | 2009-07-15 | 2015-08-19 | Sanofi-Aventis Deutschland GmbH | Drive mechanism for an injection device and an injection device with such a drive mechanism |
GB0913385D0 (en) | 2009-07-31 | 2009-09-16 | Medical House The Plc | Improved autoinjector |
JP5563075B2 (en) | 2009-07-31 | 2014-07-30 | エス・ホー・エル・グループ・アクチボラゲット | Drug container holder configuration |
GB2472578A (en) | 2009-08-10 | 2011-02-16 | Owen Mumford Ltd | Sheath removal device and needle protector |
FR2949284B1 (en) | 2009-08-24 | 2011-09-09 | Alcatel Lucent | REPRESENTATION OF PHYSICAL DEGRADATION IN AN OPTICAL COMMUNICATION NETWORK |
EP2470245B1 (en) | 2009-08-24 | 2018-05-16 | SHL Group AB | Dose reset mechanism |
EP2470150A2 (en) | 2009-08-27 | 2012-07-04 | Sanofi-Aventis Deutschland GmbH | Reminder device for drug delivery devices |
DK2470241T4 (en) | 2009-08-27 | 2023-11-20 | Sanofi Aventis Deutschland | HOUSING COMPONENT FOR A DRUG DELIVERY DEVICE |
JP5703299B2 (en) | 2009-09-07 | 2015-04-15 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Drive mechanism for drug delivery device |
DK2475408T3 (en) | 2009-09-10 | 2015-05-26 | Sanofi Aventis Deutschland | Drug container |
JP5726194B2 (en) | 2009-09-18 | 2015-05-27 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Latching and control device for integration in medical devices |
JP5878124B2 (en) | 2009-09-23 | 2016-03-08 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Assembly for drug delivery device and drug delivery device |
PL2480268T3 (en) | 2009-09-23 | 2017-03-31 | Sanofi-Aventis Deutschland Gmbh | Assembly and indicator for a drug delivery device |
DE102009048497A1 (en) | 2009-09-26 | 2011-03-31 | Haselmeier Gmbh | injection device |
TW201121600A (en) | 2009-09-29 | 2011-07-01 | Sanofi Aventis Deutschland | Assembly for a drug delivery device |
CA2774580A1 (en) | 2009-09-30 | 2011-04-07 | Sanofi-Aventis Deutschland Gmbh | Method and assembly for a drug delivery device |
CA2773928A1 (en) | 2009-09-30 | 2011-04-07 | Sanofi-Aventis Deutschland Gmbh | Injection device |
BR112012007608A2 (en) | 2009-09-30 | 2016-08-23 | Sanofi Aventis Deutschland | drive mechanism for a drug delivery device and use of an elastic element for a drive mechanism |
AR078458A1 (en) | 2009-09-30 | 2011-11-09 | Sanofi Aventis Deutschland | DRIVE ASSEMBLY, PISTON VASTAGO, DRUG DELIVERY DEVICE, AND USE OF A SPRING |
US8911402B2 (en) | 2009-09-30 | 2014-12-16 | Sanofi-Aventis Deutschland Gmbh | Drug delivery device |
EP2482874A4 (en) | 2009-09-30 | 2014-11-26 | Shl Group Ab | Medicament delivery device |
BR112012007310A2 (en) | 2009-09-30 | 2016-04-19 | Sanofi Aventis Deutschland | drive mechanism for a drug delivery device and use of a reset member for a drive mechanism |
WO2011039209A1 (en) | 2009-09-30 | 2011-04-07 | Sanofi-Aventis Deutschland Gmbh | Assembly and piston rod for a drug delivery device |
EP2482891B1 (en) | 2009-09-30 | 2016-10-26 | Sanofi-Aventis Deutschland GmbH | Resettable drive assembly and drug delivery device |
CN102548602B (en) | 2009-09-30 | 2014-07-16 | 赛诺菲-安万特德国有限公司 | Drive mechanism for a drug delivery device |
US20120283654A1 (en) | 2009-09-30 | 2012-11-08 | Sanofi-Aventis Deutschland Gmbh | Button Member for Operating a Drive Assembly |
TW201127435A (en) | 2009-09-30 | 2011-08-16 | Sanofi Aventis Deutschland | Drive mechanism for a drug delivery device |
US9555192B2 (en) | 2009-09-30 | 2017-01-31 | Sanofi-Aventis Deutschland Gmbh | Drug delivery device, assembly for a drug delivery device and method for setting up a drug delivery device |
TW201121602A (en) | 2009-09-30 | 2011-07-01 | Sanofi Aventis Deutschland | Drive assembly, piston rod, drug delivery device, and use of a spring |
JP5756468B2 (en) | 2009-09-30 | 2015-07-29 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Assembly for use in a drug delivery device |
DK2482887T3 (en) | 2009-09-30 | 2014-10-27 | Sanofi Aventis Deutschland | DRIVING MECHANISM FOR A PHARMACEUTICAL SUPPLY DEVICE |
US8882748B2 (en) | 2009-10-08 | 2014-11-11 | Palo Alto Research Center Incorporated | Transmucosal drug delivery device and method including chemical permeation enhancers |
WO2011042540A1 (en) | 2009-10-08 | 2011-04-14 | Sanofi-Aventis Deutschland Gmbh | Medicament injection device with lockout feature |
EP2485786B1 (en) | 2009-10-08 | 2020-08-19 | SHL Medical AG | Medicament delivery device |
CN102573955A (en) | 2009-10-08 | 2012-07-11 | 赛诺菲-安万特德国有限公司 | Drug delivery device with biodegradable plastic components |
US8948863B2 (en) | 2009-10-09 | 2015-02-03 | Board Of Regents, The University Of Texas System | Photokinetic ocular drug delivery methods and apparatus |
US9012590B2 (en) | 2009-10-15 | 2015-04-21 | Lubrizol Advanced Materials, Inc. | Electrostatic dissipative TPU and compositions thereof |
CA2777118A1 (en) | 2009-10-16 | 2011-04-21 | Sanofi-Aventis Deutschland Gmbh | Drug delivery device |
GB0918145D0 (en) | 2009-10-16 | 2009-12-02 | Owen Mumford Ltd | Injector apparatus |
WO2011045386A2 (en) | 2009-10-16 | 2011-04-21 | Sanofi-Aventis Deutschland Gmbh | Arrangement for use in a drug delivery device |
EP2311513A1 (en) | 2009-10-16 | 2011-04-20 | Sanofi-Aventis Deutschland GmbH | Cartridge holder assembly for a drug delivery device |
EP2490735B1 (en) | 2009-10-21 | 2015-09-16 | Owen Mumford Limited | Autoinjector |
EA023812B1 (en) | 2009-10-23 | 2016-07-29 | Массачусетс Инститьют Оф Текнолоджи | Catalytic material |
US8864718B2 (en) | 2009-10-23 | 2014-10-21 | Bang & Olufsen Medicom A/S | Auto injector with automatic needle shielding |
EP2493529B1 (en) | 2009-10-26 | 2016-03-30 | SHL Group AB | Medicament delivery device |
DK2493532T3 (en) | 2009-10-30 | 2019-10-07 | Sanofi Aventis Deutschland | Drug delivery device |
WO2011053787A2 (en) * | 2009-10-30 | 2011-05-05 | Seventh Sense Biosystems, Inc. | Systems and methods for application to skin and control of actuation, delivery and/or perception thereof |
US9737666B2 (en) | 2009-11-03 | 2017-08-22 | Sanofi-Aventis Deutschland Gmbh | Assembly for a drug delivery device and drug delivery device |
DK2496292T3 (en) | 2009-11-06 | 2014-10-06 | Shl Group Ab | DEVICE FOR MEDICINE DELIVERY |
JP2013510668A (en) | 2009-11-11 | 2013-03-28 | アルファテック スパイン, インコーポレイテッド | Method and device for securing a portal to a spine |
EP2335755A1 (en) | 2009-12-17 | 2011-06-22 | Sanofi-Aventis Deutschland GmbH | Device and method for delivery of two or more drug agents |
JP5755238B2 (en) | 2009-12-02 | 2015-07-29 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Drug delivery device and related packaging |
EP2329857A1 (en) | 2009-12-03 | 2011-06-08 | Sanofi-Aventis Deutschland GmbH | A drug delivery device |
GB0921295D0 (en) | 2009-12-04 | 2010-01-20 | Owen Mumford Ltd | Injection appaeratus |
JP5684982B2 (en) | 2009-12-04 | 2015-03-18 | 東レ・ダウコーニング株式会社 | Silicone oil emulsion, method for producing the same, and silicone oil composition |
AU2010330033B2 (en) | 2009-12-07 | 2014-10-23 | Sanofi-Aventis Deutschland Gmbh | Drive assembly for a drug delivery device and drug delivery device |
US8856501B2 (en) | 2009-12-14 | 2014-10-07 | Sandisk Technologies Inc. | Method and system for controlling operation of interconnected devices by circulating host capability without a centralized manager |
DK2512561T3 (en) | 2009-12-15 | 2016-05-09 | Shl Group Ab | DRUG DELIVERY DEVICES |
CN102770170B (en) | 2009-12-17 | 2017-05-03 | 赛诺菲-安万特德国有限公司 | Medical device and method of assembly |
CN102781499B (en) | 2009-12-18 | 2015-05-13 | 赛诺菲-安万特德国有限公司 | Piston for a cartridge and piston rod for a drug delivery device |
SG181710A1 (en) | 2009-12-18 | 2012-07-30 | Sanofi Aventis Deutschland | Dose setting mechanism with maximum dose limiting element |
EP2515973B1 (en) | 2009-12-23 | 2018-02-21 | Tecpharma Licensing AG | Injection device comprising a needle protection sleeve |
CA2783722A1 (en) | 2010-01-22 | 2011-07-28 | Sanofi-Aventis Deutschland Gmbh | Coded cartridge holder and fastener enabled by cartridge size |
US10130558B2 (en) | 2010-01-22 | 2018-11-20 | Sanofi-Aventis Deutschland Gmbh | Coded collapsible drug reservoir |
EP2351591A1 (en) | 2010-02-02 | 2011-08-03 | Sanofi-Aventis Deutschland GmbH | Assembly for a drug delivery device and drug delivery device |
EP2531235A1 (en) | 2010-02-05 | 2012-12-12 | Sanofi-Aventis Deutschland GmbH | Flexible reservoir for a medicated module |
JP5805107B2 (en) | 2010-02-05 | 2015-11-04 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Medicinal module with double needle guard |
AU2011212567B2 (en) | 2010-02-05 | 2015-01-22 | Sanofi-Aventis Deutschland Gmbh | Push rod activated medicated module |
WO2011095483A1 (en) | 2010-02-05 | 2011-08-11 | Sanofi-Aventis Deutschland Gmbh | Medicated module with time lock |
US9402963B2 (en) | 2010-02-05 | 2016-08-02 | Sanofi-Aventis Deutschland Gmbh | Medicated module with dual safety guards |
AU2011212564B2 (en) | 2010-02-05 | 2015-02-05 | Sanofi-Aventis Deutschland Gmbh | Medicated module with lockable needle guard |
DK2533834T3 (en) | 2010-02-09 | 2018-01-15 | Shl Group Ab | DRUG DELIVERY DEVICES |
CA2790190A1 (en) | 2010-02-17 | 2011-08-25 | Sanofi-Aventis Deutschland Gmbh | Automatic injection device with torsional spring |
US9227015B2 (en) | 2010-02-17 | 2016-01-05 | Sanofi-Aventis Deutschland Gmbh | Spring driven injection device with twin cartridges |
JP5797209B2 (en) | 2010-02-18 | 2015-10-21 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Automatic syringe |
CA2790193A1 (en) | 2010-02-18 | 2011-08-25 | Sanofi-Aventis Deutschland Gmbh | Auto-injector |
WO2011101375A1 (en) | 2010-02-18 | 2011-08-25 | Sanofi-Aventis Deutschland Gmbh | Auto-injector with a torsion spring |
JP5807022B2 (en) | 2010-02-18 | 2015-11-10 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Automatic syringe |
JP5872490B2 (en) | 2010-02-18 | 2016-03-01 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Clutch mechanism |
CA2789561A1 (en) | 2010-02-18 | 2011-08-25 | Sanofi-Aventis Deutschland Gmbh | Finger guard for an injection device |
JP5855022B2 (en) | 2010-02-22 | 2016-02-09 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Power transmission arrangement for automatic syringes |
EP2538996B1 (en) | 2010-02-22 | 2020-05-20 | Sanofi-Aventis Deutschland GmbH | Auto-injector with needle shroud and needle protection cap |
US9358351B2 (en) | 2010-02-22 | 2016-06-07 | Sanofi-Aventis Deutschland Gmbh | Gearbox |
AU2011221472B2 (en) | 2010-03-01 | 2013-08-29 | Eli Lilly And Company | Automatic injection device with delay mechanism including dual functioning biasing member |
GB2478349A (en) | 2010-03-05 | 2011-09-07 | Owen Mumford Ltd | Injection device having projections reducing the diameter of the syringe passage |
EP2364740A1 (en) | 2010-03-09 | 2011-09-14 | Sanofi-Aventis Deutschland GmbH | Arrangement for transferring a translation of a drive means to a plunger |
EP2364739A1 (en) | 2010-03-09 | 2011-09-14 | Sanofi-Aventis Deutschland GmbH | Re-usable autoinjector |
EP2364741A1 (en) | 2010-03-09 | 2011-09-14 | Sanofi-Aventis Deutschland GmbH | Interlock mechanism for defining an operation sequence of an auto-injector |
US9061104B2 (en) | 2010-03-09 | 2015-06-23 | Shl Group Ab | Medicament injection device |
IT1398501B1 (en) | 2010-03-10 | 2013-03-01 | Menarini Int Operations Lu Sa | AUTOINECTOR DEVICE FOR TWO DRUG DOSES |
JP5482889B2 (en) | 2010-03-15 | 2014-05-07 | 富士通株式会社 | Wireless base station |
EP2547382B1 (en) | 2010-03-16 | 2021-08-04 | Sanofi-Aventis Deutschland GmbH | Controlling a motor of an injection device |
TW201808357A (en) | 2010-03-22 | 2018-03-16 | 賽諾菲阿凡提斯德意志有限公司 | Device, method, system and computer program for drtermining information related to a medical device |
AU2011231691B2 (en) | 2010-03-25 | 2015-01-22 | Sanofi-Aventis Deutschland Gmbh | Medicated module with automatic reservoir engagement |
JP5815015B2 (en) | 2010-03-25 | 2015-11-17 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Medicinal module with user choice |
TW201200190A (en) | 2010-03-26 | 2012-01-01 | Sanofi Aventis Deutschland | Electro-mechanical drug delivery device |
CA2794816A1 (en) | 2010-03-31 | 2011-10-06 | Sanofi-Aventis Deutschland Gmbh | Set of drug delivery devices with tactile or visual enhancements |
KR101724784B1 (en) | 2010-03-31 | 2017-04-07 | 에스에이치엘 그룹 에이비 | Medicament delivery device |
US8986259B2 (en) | 2010-03-31 | 2015-03-24 | Sanofi-Aventis Deutschland Gmbh | Piston rod assembly for a drug delivery device |
WO2011126439A1 (en) | 2010-04-07 | 2011-10-13 | Shl Group Ab | Medicament delivery device |
US20130150802A1 (en) | 2010-04-09 | 2013-06-13 | Sanofi-Aventis Deutschland Gmbh | Coded cap for use with a drug delivery device |
SG184501A1 (en) | 2010-04-23 | 2012-11-29 | Sanofi Aventis Deutschland | Coded fastener assembly |
CN102958550B (en) | 2010-04-23 | 2016-05-18 | 赛诺菲-安万特德国有限公司 | Cartridge case retainer and alignment interface |
MY163102A (en) | 2010-04-23 | 2017-08-15 | Sanofi Aventis Deutschland | Coded cartridge assembly |
CA2801147C (en) | 2010-06-03 | 2015-02-24 | Shl Group Ab | Medicament delivery device |
WO2011154480A2 (en) | 2010-06-11 | 2011-12-15 | Sanofi-Aventis Deutschland Gmbh | A drive assembly for a medication delivery device and medication delivery device |
WO2011163347A2 (en) | 2010-06-23 | 2011-12-29 | Seventh Sense Biosystems, Inc. | Sampling devices and methods involving relatively little pain |
US8728040B2 (en) | 2010-06-23 | 2014-05-20 | Tcb Medical Devices, Llc | Injector for auto-injection of medication and associated method of use |
US8790379B2 (en) | 2010-06-23 | 2014-07-29 | Zimmer, Inc. | Flexible plate fixation of bone fractures |
EP3639775B1 (en) | 2010-06-23 | 2024-07-17 | Zimmer, Inc. | Flexible plate fixation of bone fractures |
EP2588173B1 (en) | 2010-07-02 | 2015-10-07 | Sanofi-Aventis Deutschland GmbH | Safety device for a pre-filled syringe and injection device |
PL2588168T3 (en) | 2010-07-02 | 2015-08-31 | Sanofi Aventis Deutschland | Safety device for a pre-filled syringe and injection device |
RU2572738C2 (en) | 2010-07-02 | 2016-01-20 | Санофи-Авентис Дойчланд Гмбх | Safety device for prefilled syringe and injection device |
JP5901627B2 (en) | 2010-07-02 | 2016-04-13 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Safety devices for drug-filled syringes and injection devices |
EP2588165B1 (en) | 2010-07-02 | 2020-06-17 | Sanofi-Aventis Deutschland GmbH | Safety device for a pre-filled syringe, injection device and injection kit |
NZ604014A (en) | 2010-07-02 | 2014-04-30 | Sanofi Aventis Deutschland | Injection device with needle shield |
NZ604075A (en) | 2010-07-02 | 2014-03-28 | Sanofi Aventis Deutschland | Safety device for a pre-filled syringe and injection device |
EP2588170A2 (en) | 2010-07-02 | 2013-05-08 | Sanofi-Aventis Deutschland GmbH | Needle shield for a safety device, safety device and injection device |
WO2012006694A1 (en) | 2010-07-16 | 2012-01-19 | Marc Keersmaekers | Lift system for use in a scaffold |
JP2013533074A (en) | 2010-08-13 | 2013-08-22 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Connector for drug delivery device reservoir |
US9152829B2 (en) | 2010-08-19 | 2015-10-06 | Sanofi-Aventis Deutschland Gmbh | Method and system for determining information related to a drug reservoir using an electronic sensor |
US20120101475A1 (en) | 2010-10-21 | 2012-04-26 | Meridian Medical Technologies, Inc. | High Efficiency Auto-Injector |
WO2012090186A1 (en) | 2010-12-30 | 2012-07-05 | Meridian Medical Technologies, Inc. | Slip-resistant autoinjectors |
US9283020B2 (en) | 2011-01-03 | 2016-03-15 | Warsaw Orthopedic, Inc. | Surgical tack delivery system, method and kit |
WO2012122643A1 (en) | 2011-03-11 | 2012-09-20 | University Of Saskatchewan | Injection assist device and method |
US20120253314A1 (en) | 2011-03-30 | 2012-10-04 | Ziv Harish | Palm-controlled injectors |
KR20120119280A (en) | 2011-04-21 | 2012-10-31 | 한국전자통신연구원 | Capacitor |
US8496619B2 (en) | 2011-07-15 | 2013-07-30 | Antares Pharma, Inc. | Injection device with cammed ram assembly |
JP6141846B2 (en) | 2011-08-24 | 2017-06-14 | ユニトラクト シリンジ プロプライエタリイ リミテッドUnitract Syringe Pty Ltd | Auto-injector for retractable prefilled syringes |
-
2013
- 2013-04-05 US US13/857,859 patent/US9950125B2/en active Active
- 2013-04-05 AU AU2013203784A patent/AU2013203784A1/en not_active Abandoned
- 2013-04-05 EP EP23152375.4A patent/EP4186545A1/en active Pending
- 2013-04-05 WO PCT/US2013/035509 patent/WO2013152323A1/en active Application Filing
- 2013-04-05 CA CA2868500A patent/CA2868500C/en active Active
- 2013-04-05 CN CN201380028911.9A patent/CN104487114A/en active Pending
- 2013-04-05 KR KR1020147030766A patent/KR20150011346A/en not_active Application Discontinuation
- 2013-04-05 EP EP13772839.0A patent/EP2833944A4/en not_active Ceased
- 2013-04-05 JP JP2015504755A patent/JP6457383B2/en active Active
-
2016
- 2016-08-17 US US15/238,901 patent/US20170043103A1/en not_active Abandoned
-
2018
- 2018-10-01 US US16/149,032 patent/US10821072B2/en active Active
- 2018-12-20 JP JP2018237910A patent/JP2019058744A/en active Pending
-
2020
- 2020-10-02 US US17/062,196 patent/US11771646B2/en active Active
-
2023
- 2023-08-21 US US18/452,743 patent/US20230390187A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
JP6457383B2 (en) | 2019-01-23 |
EP4186545A1 (en) | 2023-05-31 |
CA2868500A1 (en) | 2013-10-10 |
US10821072B2 (en) | 2020-11-03 |
KR20150011346A (en) | 2015-01-30 |
US20190030260A1 (en) | 2019-01-31 |
CA2868500C (en) | 2020-04-21 |
AU2013203784A1 (en) | 2013-10-24 |
EP2833944A4 (en) | 2016-05-25 |
US11771646B2 (en) | 2023-10-03 |
US9950125B2 (en) | 2018-04-24 |
CN104487114A (en) | 2015-04-01 |
JP2019058744A (en) | 2019-04-18 |
WO2013152323A1 (en) | 2013-10-10 |
EP2833944A1 (en) | 2015-02-11 |
US20130303985A1 (en) | 2013-11-14 |
JP2015516845A (en) | 2015-06-18 |
US20170043103A1 (en) | 2017-02-16 |
US20210015741A1 (en) | 2021-01-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11771646B2 (en) | Needle assisted jet injection administration of testosterone compositions | |
US11844804B2 (en) | Administration of testosterone compositions | |
US20220125713A1 (en) | Hematocrit Modulation Through Needle Assisted Jet Injection of Testosterone | |
US20050096598A1 (en) | Safety shield system for a syringe | |
MXPA06010227A (en) | Intradermal syringe and needle assembly. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
STPP | Information on status: patent application and granting procedure in general |
Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION |
|
STPP | Information on status: patent application and granting procedure in general |
Free format text: NON FINAL ACTION MAILED |