NZ715742B2 - Reconstitution methods - Google Patents
Reconstitution methods Download PDFInfo
- Publication number
- NZ715742B2 NZ715742B2 NZ715742A NZ71574212A NZ715742B2 NZ 715742 B2 NZ715742 B2 NZ 715742B2 NZ 715742 A NZ715742 A NZ 715742A NZ 71574212 A NZ71574212 A NZ 71574212A NZ 715742 B2 NZ715742 B2 NZ 715742B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- plunger
- composition
- compositions
- compartment
- mixing
- Prior art date
Links
- 239000000203 mixture Substances 0.000 claims abstract description 153
- 238000002156 mixing Methods 0.000 claims abstract description 57
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 50
- 238000010008 shearing Methods 0.000 claims abstract description 38
- 229960000711 alprostadil Drugs 0.000 claims description 22
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical group CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 claims description 22
- 239000002550 vasoactive agent Substances 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 3
- 238000007906 compression Methods 0.000 claims description 2
- 201000001880 sexual dysfunction Diseases 0.000 abstract description 8
- 231100000872 sexual dysfunction Toxicity 0.000 abstract description 8
- 208000010195 Onychomycosis Diseases 0.000 abstract description 5
- 230000000994 depressed Effects 0.000 abstract 2
- 239000004615 ingredient Substances 0.000 description 17
- 150000001875 compounds Chemical class 0.000 description 15
- 201000010099 disease Diseases 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 239000000463 material Substances 0.000 description 11
- 206010057672 Male sexual dysfunction Diseases 0.000 description 10
- 239000007788 liquid Substances 0.000 description 9
- 210000003708 Urethra Anatomy 0.000 description 8
- 229940079593 drugs Drugs 0.000 description 8
- 239000000825 pharmaceutical preparation Substances 0.000 description 8
- 239000003085 diluting agent Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000000699 topical Effects 0.000 description 6
- 206010057671 Female sexual dysfunction Diseases 0.000 description 5
- 210000003128 Head Anatomy 0.000 description 5
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N Terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- 229920003023 plastic Polymers 0.000 description 5
- 238000002203 pretreatment Methods 0.000 description 5
- 229960002722 terbinafine Drugs 0.000 description 5
- 210000001519 tissues Anatomy 0.000 description 5
- 210000003491 Skin Anatomy 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 230000004059 degradation Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 235000014113 dietary fatty acids Nutrition 0.000 description 4
- 239000000194 fatty acid Substances 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000006072 paste Substances 0.000 description 4
- 230000035515 penetration Effects 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- -1 vaccines Substances 0.000 description 4
- 229960005486 vaccines Drugs 0.000 description 4
- 210000004247 Hand Anatomy 0.000 description 3
- 210000001215 Vagina Anatomy 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 230000000977 initiatory Effects 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 230000002335 preservative Effects 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 241001340526 Chrysoclista linneella Species 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 210000003811 Fingers Anatomy 0.000 description 2
- 229960004873 LEVOMENTHOL Drugs 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N Lauric acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- OYHQOLUKZRVURQ-IXWMQOLASA-N Linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229940041616 Menthol Drugs 0.000 description 2
- TUNFSRHWOTWDNC-UHFFFAOYSA-N Myristic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N Oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N Palmitic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- SECPZKHBENQXJG-FPLPWBNLSA-N Palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N Stearic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 231100000494 adverse effect Toxicity 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000000202 analgesic Effects 0.000 description 2
- 230000000903 blocking Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 230000003247 decreasing Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000001965 increased Effects 0.000 description 2
- 239000002085 irritant Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000006011 modification reaction Methods 0.000 description 2
- 230000003000 nontoxic Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000003961 penetration enhancing agent Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000005057 refrigeration Methods 0.000 description 2
- 230000000717 retained Effects 0.000 description 2
- 230000001568 sexual Effects 0.000 description 2
- 231100000486 side effect Toxicity 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- DTOSIQBPPRVQHS-PDBXOOCHSA-N α-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 2
- BGRXBNZMPMGLQI-UHFFFAOYSA-N 2-octyldodecyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(CCCCCCCC)CCCCCCCCCC BGRXBNZMPMGLQI-UHFFFAOYSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 229940114079 Arachidonic Acid Drugs 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N Arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 1
- 210000004369 Blood Anatomy 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- 210000003169 Central Nervous System Anatomy 0.000 description 1
- 210000003756 Cervix Mucus Anatomy 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N Cetyl alcohol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 210000003029 Clitoris Anatomy 0.000 description 1
- JYGXADMDTFJGBT-VWUMJDOOSA-N Cortisol Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 1
- HSMMSDWNEJLVRY-UHFFFAOYSA-N DDAIP Chemical compound CCCCCCCCCCCCOC(=O)C(C)N(C)C HSMMSDWNEJLVRY-UHFFFAOYSA-N 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N Dodecanol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N Ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 210000000887 Face Anatomy 0.000 description 1
- 206010062641 Female sexual arousal disease Diseases 0.000 description 1
- 229940096919 Glycogen Drugs 0.000 description 1
- BYSGBSNPRWKUQH-UJDJLXLFSA-N Glycogen Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](O)[C@@H](O[C@@H]2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)O1 BYSGBSNPRWKUQH-UJDJLXLFSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- AXISYYRBXTVTFY-UHFFFAOYSA-N Isopropyl myristate Chemical compound CCCCCCCCCCCCCC(=O)OC(C)C AXISYYRBXTVTFY-UHFFFAOYSA-N 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N Isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 241001313288 Labia Species 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 229960004488 Linolenic Acid Drugs 0.000 description 1
- 235000021360 Myristic acid Nutrition 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N Oleyl alcohol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000021319 Palmitoleic acid Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000004698 Polyethylene (PE) Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N Stearyl alcohol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 240000000280 Theobroma cacao Species 0.000 description 1
- 210000003813 Thumb Anatomy 0.000 description 1
- 229940029983 VITAMINS Drugs 0.000 description 1
- 229940046009 Vitamin E Drugs 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 229940021016 Vitamin IV solution additives Drugs 0.000 description 1
- UGHVFDVVZRNMHY-NXVVXOECSA-N [(Z)-octadec-9-enyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCCCCCCC\C=C/CCCCCCCC UGHVFDVVZRNMHY-NXVVXOECSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive Effects 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000037007 arousal Effects 0.000 description 1
- 230000001580 bacterial Effects 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 235000005764 cacao Nutrition 0.000 description 1
- 235000005767 cacao Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229940074979 cetyl palmitate Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000002254 contraceptive Effects 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 230000002939 deleterious Effects 0.000 description 1
- IPWWTXFQEUNUNX-UHFFFAOYSA-N dodecyl 2-(dimethylamino)propanoate;hydrochloride Chemical compound Cl.CCCCCCCCCCCCOC(=O)C(C)N(C)C IPWWTXFQEUNUNX-UHFFFAOYSA-N 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000002314 glycerols Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000001861 immunosuppresant Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 239000005414 inactive ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 230000000670 limiting Effects 0.000 description 1
- 235000020778 linoleic acid Nutrition 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- PXDJXZJSCPSGGI-UHFFFAOYSA-N palmityl palmitate Chemical compound CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 1
- 230000036961 partial Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000000149 penetrating Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutic aid Substances 0.000 description 1
- 238000005020 pharmaceutical industry Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical class CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 230000001681 protective Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 230000001954 sterilising Effects 0.000 description 1
- 235000020238 sunflower seed Nutrition 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000001702 transmitter Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 150000003712 vitamin E derivatives Chemical class 0.000 description 1
- 229930003231 vitamins Natural products 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
Abstract
reconstitution device, particularly a reconstitution device for combining two separated components of a pharmaceutical composition. The reconstitution device comprising a first (12, see figure 10) and second (14) housings, a conduit, a first (50), second (52) and third (54) plunger, a plunger rod, a moveable member and a shearing channel (32). The first and second housings are immovably engageable together. The conduit comprises an internal passageway, formed in the first housing, the internal passageway having a dispensing end and an inlet end. The first plunger is mounted within the passageway, proximate the dispensing end. The second plunger is mounted within the passageway, proximate the inlet end. The third plunger is mounted within the passageway intermediate the first and second plungers, the three plungers defining a first compartment (74) and a second compartment (76). The plunger rod extends at least partially within the internal passageway and may comprise a shaft (60) and an enlarged head (62). The moveable member is located within the second housing and engages the first plunger. The shearing channel is formed in the side wall of the conduit and permits the mixing of the contents located in the first and second compartments. Preferably, when the plunger rod is depressed the plungers translate along the channel until a first component (72) may travel via the shearing channel and mix with a second component (70), within the first compartment. The plunger is then allowed to return upwards, the moveable member acting on the first plunger to transfer the composition comprising both components into the second compartment. The first and second housings may be decoupled allowing the composition to be applied from the dispensing end of the internal passageway. Also disclosed is a method of filling the reconstitution device comprising placing, within the internal passageway, the first plunger, the first component, the third plunger, the second component, the second plunger and then the plunger rod. The device and/or pharmaceutical composition therein may be used to treat nail fungus, or sexual dysfunction. a moveable member and a shearing channel (32). The first and second housings are immovably engageable together. The conduit comprises an internal passageway, formed in the first housing, the internal passageway having a dispensing end and an inlet end. The first plunger is mounted within the passageway, proximate the dispensing end. The second plunger is mounted within the passageway, proximate the inlet end. The third plunger is mounted within the passageway intermediate the first and second plungers, the three plungers defining a first compartment (74) and a second compartment (76). The plunger rod extends at least partially within the internal passageway and may comprise a shaft (60) and an enlarged head (62). The moveable member is located within the second housing and engages the first plunger. The shearing channel is formed in the side wall of the conduit and permits the mixing of the contents located in the first and second compartments. Preferably, when the plunger rod is depressed the plungers translate along the channel until a first component (72) may travel via the shearing channel and mix with a second component (70), within the first compartment. The plunger is then allowed to return upwards, the moveable member acting on the first plunger to transfer the composition comprising both components into the second compartment. The first and second housings may be decoupled allowing the composition to be applied from the dispensing end of the internal passageway. Also disclosed is a method of filling the reconstitution device comprising placing, within the internal passageway, the first plunger, the first component, the third plunger, the second component, the second plunger and then the plunger rod. The device and/or pharmaceutical composition therein may be used to treat nail fungus, or sexual dysfunction.
Description
FJELD OF THE INVENTION
The present invention relates to methods for reconstituting and
relates to reconstitution devices suitable for reconstituting many different materials.
Furthermore, the present invention includes methods of treatment and methods of use
related to a reconstitution device or apparatus.
BACKGROUND OF THE DISCLOSURE
In the pharmaceutical industry, the step of reconstituting a drug or
other material is well known. Many pharmaceutical compositions are not capable of
being stored for extended periods of time since their potency may change. In order to
overcome this problem of a short shelf life, such pharmaceutical products are stored as
a solid component and a liquid component. Prior to use, the two components must be
mixed together.
Furthermore, while preservatives are effective in preserving some
ingredients included in a pharmaceutical composition, such preservatives may cause
adverse reactions with other ingredients of the pharmaceutical composition, namely
the active ingredient, and result in degradation and/or spoilage. In some situations,
refrigeration may be used to combat degradation or spoilage of a pharmaceutical
composition. However, refrigeration is not always accessible and administration of a
cooled pharmaceutical composition may reduce the effectiveness, namely solubility
and penetration, of the pharmaceutical composition.
Although many reconstitution systems are directed for use with a
powdered solid component and a diluent component, there are also occasions when
other forms of material may be utilized. Thus, the reconstitution system may employ
two liquids, or a semi liquid component such a paste along with a second component
which is typically a liquid.
Several problems must be addressed in any reconstitution device
such as the problem of obtaining a proper mixture. For highly soluble products such
as a powder and a diluent therefore, a simple mixing of the two components is
sufficient. Typically in such an arrangement, the diluent and dry components are
stored in separate compartments of a device. The device will include a by-pass such
to go through the by-pass to mix with
that pressure on a plunger will cause the liquid
the dry ingredient. Usually a simple shaking of the mixture is sufficient to assure that
the mixture is properly constituted.
However, certain pharmaceutical products require a more thorough
mixing and the conventional devices cannot be used. One other problem which is
frequently encountered is that the components to be mixed are utilized in a small
quantity and conventional mixing devices are not suitable. This is particularly the
case when one of the components is in the form of a paste into which a liquid like
constituent must be mixed.
Furthermore, poor application of a pharmaceutical composition can
hinder the effectiveness of the pharmaceutical composition. Some advances in the
ergonomics and delivery of pharmaceutical compositions have been made, see for
example U.S. Patent No. 6,224,573 (Yeager et al.). However, previous applicators
that combined more than one composition together prior to administration do not have
sufficient mixing mechanisms to achieve optimal composition storage, mixing, and
application. Thus, there remain needs for methods of treating and devices to
overcome all the issues that remain with the storage, mixing, and administration of
pharmaceutical compositions.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a reconstitution
system or device which is suitable for reconstituting small amounts of pharmaceutical
compounds.
It is a further object of the present invention to provide methods for
the reconstitution of pharmaceutical compounds and methods of treatment. Some
embodiments are suitable for reconstituting small amounts of a pharmaceutical
compositions and using the pharmaceutical composition for the treatment of sexual
dysfunction.
[0009a] In an aspect of the invention there is provided amethod of mixing
comprising:
filling a device with at least two compositions;
storing said at least two compositions; and
mixing said at least two compositions with said device
wherein said device comprises:
at least one housing element capable of containing at least two compositions; and
at least one dispensing element for applying said at least two compositions
comprising a spring member.
[0010] According to one aspect of the present invention, there is provided a
reconstitution device comprising a device suitable for mixing a first component with a
second component, the device comprising first and second housings, the first and second
housings being engageable together, a conduit having an internal passageway formed in
the first housing, the internal passageway having a dispensing end and an inlet end, a first
plunger mounted in the internal passageway proximate the dispensing end, a second
plunger mounted in the internal passageway proximate the inlet end, a third plunger
mounted in the internal passageway intermediate the first and second plungers, the first
and third plungers defining a first compartment therebetween, the second and third
plungers defining a second compartment therebeween, a plunger rod at least partially
within the internal passageway at the inlet end, a moveable member located in the second
housing, the moveable member engaging the first plunger, and a shearing channel formed
in a side wall of the conduit to permit mixing of contents located in the first and second
compartments.
According to a further aspect of the present invention, there is also
provided a device for mixing a first component with a second component, the device
comprising first and second housings, the first and second housing each having a partial
screw thread formed on an exterior surface thereof, the first and second housings being
engageable together by means of the screw threads, a conduit having an internal
passageway formed in the first housing, the internal passageway having a dispensing end
and an inlet end, a first plunger mounted in the internal passageway proximate the
dispensing end, a second plunger mounted in the internal passageway proximate the inlet
(11641272_1):KZA
end, a third plunger mounted in the internal passageway intermediate the first and second
plungers, the first and third plungers defining a first compartment therebetween, the
second and third plungers defining a second compartment therebetween, a plunger rod at
least partially within the internal passageway at the inlet end, a moveable member located
in the second housing, the moveable member engaging the first plunger, the moveable
member having at least one leg extending upwardly therefrom, the upwardly extending
leg engaging the first housing such that the first and second housing cannot be disengaged
from an initial first position, the arrangement being such that when the plunger rod is
moved to
(11641272_1):KZA
commence transfer from the second compartment to the first compartment, the leg on
the moveable member disengages from the first housing to permit rotatable movement
of the first and second housings.
According to a still further aspect of the present invention, there is
also provided a method of filling a reconstitution device comprising the steps of
supplying first and second housings, the first and second housings being engageable
together, a conduit having an internal passageway formed in the first housing, the
internal passageway having a dispensing end and an inlet end, a moveable member
mounted in the second housing, placing a first plunger on the moveable member, the
plunger sealing the dispensing end of the internal passageway, inserting a first
material in the internal passageway on the first plunger, inserting a second plunger in
the internal passageway from the inlet end to seal the first material in a first
compartment formed between the first and second plungers, placing a second material
on top of the second plunger, inserting a third plunger to seal the second material
between the second and third plungers, and placing a plunger rod adjacent the third
plunger.
In one embodiment, the device, as above mentioned, includes first
and second housings. The first and second housings are engageable together such that
they may be retained in the assembled position for a period of time as will be
discussed hereinbelow. The first and second housings are releasable.
Within one of the housings, there is provided a conduit having a
hollow passageway therein. The passageway has three plungers mounted therein for
containing the ingredients to be reconstituted. In one embodiment, there is provided a
first plunger which is located proximate the outlet or dispensing end of the conduit as
will be discussed in greater detail hereinbelow. A second plunger is mounted in the
internal passageway closer to the inlet end of the conduit. However, this second
plunger is not located at the very end, but rather is usually proximate the middle of the
conduit.
A third plunger mounted in the passageway is intermediate of the
first and second plungers. The first and third plungers define a first compartment for
receiving a first ingredient while the second and third plungers define a second
compartment therebetween for containing a second ingredient. Typically, the second
compartment will contain the less viscous of the ingredients. A shearing channel is
formed in the side wall of the conduit, again for reasons which will be discussed
hereinbelow. The shearing channel is initially at least partially covered by the third
plunger so as to maintain the ingredients apart.
A plunger rod is utilized to exert pressure or push on the second
plunger. This results in movement of the third plunger such that access to the shearing
channel is obtained. Subsequently, the ingredient in the second compartment will pass
through the shearing channel to mix with the component in the first compartment.
In one embodiment, a spring member is provided which is arranged
to exert pressure or bias the first plunger. Thus, after transferring the ingredient from
the second compartment to the first compartment, a mixture or admixture is achieved.
Subsequently, with release of the pressure on the plunger rod, the spring will cause the
first plunger to move rearwardly such that the mixture or admixture is again forced to
pass through the shearing channel. This can be repeated several times to ensure that
the composition formed by the at least two ingredients is properly mixed. Naturally,
one could use the finger of the user instead of the spring.
To assist in proper mixing, the shearing channel is sized to provide a
relatively small cross-sectional area such that significant shearing is obtained.
Typically, the shearing channel will have a diameter of less than 1 mm. In alternative
embodiments, the diameter of the shearing channel is greater than 1 mm, less than 1
mm, 0.5 mm, or 0.3 mm. In other embodiments, the shearing channel does not have a
fixed diameter; rather, the shearing channel is tapered.
As previously mentioned, the device is particularly suited for mixing
of small amounts. In some instances, the total volume of the constituents would range
between 0.1 and 0.2 of a cc. In alternative embodiments, the total volume is greater
than 10 cc, less than 10 cc, 5 cc, 1 cc, or 0.5 cc.
The moveable member mounted m the second housing in one
embodiment is connected to the first plunger. In order to do so, the moveable member
has a small rod like element with an enlarged end in some embodiments. The
enlarged end would enter the plunger such that the plunger will move back and forth
with the moveable member.
The plunger rod is positioned to initially contact the second plunger.
Thus, a portion of the plunger fits within the passageway while a further portion
extends to the end of the housing which is open and thus forms a head for applying
pressure to the plunger rod by the thumb or a finger of the user.
To prevent accidental movement of the plunger rod, the head is
retained in position by a projection on the interior wall of the housing. The projection
is sufficient to maintain the plunger rod in position until sufficient pressure is applied
to the head.
Once the initial pressure is applied to the plunger rod, it will start
moving the second plunger downwardly and apply pressure to the ingredient in the
second compartment. This in turn will cause sufficient movement of the third plunger
such that access is had to the shearing channel. The liquid will then mix with the
ingredient in the first compartment. Upon releasing the plunger rod, the spring will
apply sufficient pressure to the moveable member which in turn will move the first
plunger rearwardly and force the mixture to again pass through the shearing channel.
In some embodiments, these steps are repeated. Instead of using the spring to move
the moveable member, a manual arrangement wherein a digit of the user may be
employed.
In one embodiment, the initial movement of the third plunger will
cause the disengagement of the first and second housings to thereby permit the
housings to be disengaged when so desired. This arrangement provides the advantage
that the user cannot access the ingredients without at least having gone through one
mixing operation.
The present invention also includes methods of reconstitution and
methods of treatment with reconstituted compositions, namely pharmaceutical
compositions. Although the some embodiments have compositions for reconstitution
and use for treatment are pharmaceutical compositions suitable for the treatment of
sexual dysfunction, the methods disclosed herein are suitable for other compositions,
such as cosmetics, foods, and vaccines.
BRIEF DESCRIPTION OF THE DRAWINGS
Having thus generally described the invention, reference will be
made to the accompanying drawings illustrating embodiments thereof in which.
Figure 1 is a perspective view of a reconstitution device according to
an embodiment of the present invention;
Figure 2 is a side elevational view thereof;
Figure 3 is a top plan view thereof;
Figure 4 is an exploded view of the reconstitution device;
Figure 5 is a cross sectional view of a lower portion of the
reconstitution device;
Figure 6 is a cross sectional view similar to Figure 4 but rotated
through 90 degrees;
Figure 7 Is a cross sectional view of the upper portion of the
reconstitution device;
Figure 8 is a cross sectional and exploded view of both housings
forming the reconstitution device;
Figure 9 is cross sectional view illustrating the assembled
reconstitution device;
Figure 10 is a cross sectional view similar to Figure 8 illustrating
commencement of the reconstitution constituting step;
Figures 11 to 14 are cross sectional views illustrating the functioning
of the reconstitution device;
Figures 15 and 16 are cross sectional views illustrating the separating
of the two housings for application of the contents; and
Figure 17 is a cross sectional view of one of the housings showing an
alternative embodiment.
DETAILED DESCRIPTION OF THE EMBODIMENTS
DEFINITIONS.
Unless otherwise stated, the following terms used in this application,
including the specification and claims, have the definitions given below. As used in
"a", "an", and "the"
the specification and the appended claims, the singular forms
include plural referents unless the context clearly dictates otherwise.
The term "administer" or "administration" means the act of giving a
pharmaceutical composition to a subject.
The term "compound", "composition", "ingredient", and
"component" may sometimes be used interchangeably to refer one or more chemical
components.
"Disease" means any disease, condition, symptom, or indication.
The term "drug" or "pharmaceutically active agent" as used herein is
intended to mean a compound or composition of matter which, when administered to
an organism/subject, which is human or animal, induces a desired pharmacologic
and/or physiologic effect by local and/or systemic action.
An "effective amount" means an amount of a compound that, when
administered to a subject for treating a disease, is sufficient to effect such treatment
for the disease or condition. The "effective amount" will vary depending on the
compound, the disease state being treated, the severity or the disease being treated, the
age and relative health of the subject, the route and form of administration, the
judgment of the attending medical or veterinary practitioner and other factors.
As used herein "excipient" means a component or an ingredient that
1s acceptable in the sense of being compatible with the other components of the
formulation and not deleterious to a subject to which the formulation is to be
administered.
The term "immediately before" or "immediately prior" generally
means less than two hours before application of a composition or before the desired
next step; however, this term is not limited to this timeframe because the chemical
properties or desired state of a pharmaceutical composition may require a timeframe
more than two hours before proceeding with the next step.
The term "immediately after" or "immediately following" generally
means less than two hours after application of a composition before the desired next
step; however, this term is not limited to this timeframe because the chemical
properties or desired state of a pharmaceutical composition may require a timeframe
more than two hours before proceeding with the next step.
"Optional" or "optionally" means that the subsequent described
event or circumstance may but need not occur, and that the description includes
instances where the event or circumstances occurs and instances in which it does not
occur.
The term "penetration enhancer" means a chemical compound that
increases the permeability of the skin to a drug.
"Pharmaceutical compositions" means a composition that is
generally safe, non-toxic, and neither biologically nor otherwise undesirable and
includes that which is actable for veterinary as well as human pharmaceutical use.
"Pharmaceutically acceptable" means that which is useful m
preparing a pharmaceutical composition that is generally safe, non-toxic, and neither
biologically nor otherwise undesirable and includes that which is actable for
veterinary as well as human pharmaceutical use. This language may also include
pharmaceutically acceptable salts of a pharmaceutically acceptable composition.
"Subject" means mammals and non-mammals and the term does not
denote a particular age or sex.
The term "pharmacological effect" as used herein encompasses
effects produced in the subject that achieve the intended purpose of a therapy.
"Transdermal" application or drug delivery means delivery of a drug
by passage into and though the skin and/or the underlying tissues and into the blood
stream.
"Treating" or "treatment" of a disease includes preventing the
disease, inhibiting the disease, and/or relieving the effects of a disease.
The methods and apparatuses disclosed herein can be used in the
mixing and/or application of numerous different compositions, including vaccines,
medicaments, pharmaceutical compositions, cosmetics, and food products. Although
the some embodiments include applications and methods for pharmaceutical
compositions, one skilled in the art will appreciate applicability of this disclosure in
other areas.
Referring to the drawings in greater detail and by reference
characters thereto, there is illustrated a reconstitution device which is generally
designated by reference numeral 10.
Referring to Figure 1, an embodiment of a reconstitution device 10
includes a first housing generally designated by reference numeral 12 and a second
housing generally designated by reference numeral 14. First housing 12 includes a
wall 16, wall 16 having first projections 18 located at a first distance from the top
thereof and second projections 20 at a second distance from the top thereof. In the
illustrated embodiment, there are provided two such projections 18 and 20; it will be
understood that in alternative embodiments, one or more is utilized.
At a narrower end 22 of first housing 12, there is provided a pair of
screw threads 24, 26 for reasons which will become apparent hereinbelow. Narrower
end 22 also defines first and second recesses 53, 55 intermediate screw threads 24, 26.
A conduit 28 is located interiorly of first housing 12 and includes an
internal passageway 30 extending therethrough. A shearing recess 32 is provided
within the interior wall of conduit 28.
A ring member generally designated by reference numeral34 mounts
over narrower end 22 of first housing 12.
On a wall 35 of second housing 14, there are provided a set of lugs
36 which act as threads for engaging with screw threads 24, 26. An end cover 38
covers the larger end of second housing 14 and is secured thereto by adhesives or
welding or the like. End cover 38 includes a centering structure 40.
Mounted interiorly of second housing 14 is a moveable member 42.
As may be seen in the drawings, moveable member 42 is provided with a center post
44 having an enlarged portion 45. Moveable member 42 has a spring recess 46
formed therein to receive a spring 48. At the other end, spring 48 is mounted around
centering structure 40. Moveable member 42 also has a guide rib 47. Guide rib 47 is
designed to fit within a channel 51 formed in an inner wall 57 of second housing 14.
Moveable member 42 also has first and second legs 43, 49 extending upwardly
therefrom. In an initial position, legs 43, 49 fit within recesses 53 and 55 which will
then block relative rotation of housings 12, 14 with respect to each other. Thus, the
housings cannot be easily unscrewed until moveable member 42 is moved out of
position.
Reconstitution device 10 includes a first plunger 50 which is situated
near the dispensing end of conduit 28. A second plunger 52 is located rearwardly
towards the inlet end of conduit 28 while a third plunger 54 is situated therebetween.
It will be noted that first plunger 50 has a recess 56 to receive center post 44 of
moveable member 42.
Third plunger 54 has a side wall 80 with a concave structure. A first
end wall 82 is relatively flat or planar while end wall 84 has a somewhat conical
configuration. First plunger 50 has a side wall 86 with a plurality of concave recesses
therein and end wall 88 (which faces third plunger 54) has a conical configuration.
Similarly, second plunger 52 also has a pair of concave recesses formed therein and an
end wall 92 which is somewhat conical in configuration.
A plunger rod generally designated by reference numeral 58 is
situated within conduit 28. Plunger rod 58 includes a stem portion 60 which abuts
second plunger 52 and a head 62 which fills the open end of first housing 12. Head 62
has at least one aperture 64 which are designed to receive or engage first projections
18. In some embodiments, the device contains two recesses or more than two
recesses. Stem 60 also has a rib 66 which functions as a guide for the movement of
plunger rod 58 and which engages in a slot formed in conduit 28.
The first and third plungers define therebetween a first compartment
74 while second and third plungers define therebetween a second compartment 76.
Within first compartment 74, there is provided a first component 70.
In one embodiment, the first component 70 is in the form of a powder, paste or other
fluid. Second compartment 76 contains a second component 72 which typically will
be a less viscous material such a liquid. Both compartments 74 and 76 are thus sealed
from any contamination.
As shown m Figure 9, pressure on plunger rod 58 will cause
movement of second plunger 52 and third plunger 54. Third plunger 54 will advance
to a point such that shearing recess 32 is aligned with both first compartment 74 and
second compartment 7 6 permitting a mixture 78 to be formed. The initial movement
of plunger rod 58 will cause moveable member 42 to move out of its position blocking
rotation of housings 12, 14. After removal of the pressure, as shown in Figure 11,
spring 48 will exert pressure on moveable member 42 which in turn will drive second
plunger 52 rearwardly or upwardly as shown in the drawing. The mixture 78 will then
flow back into second compartment 76. A continuing back and forth movement is
exerted such that continued passage through shearing recess 32 will ensure adequate
mixing of the composition 78. The spring 48 will not cause moveable member 42 to
return to its original position due to projection 20.
After repeating the steps for the desired number of times, first
housing 12 and second housing 14 are separated and mixture 78 is exposed for use.
In the embodiment of Figure 16, there is provided a different type of
shearing channel 122. As will be noted, shearing channel 122 is formed within the
wall defining conduit 28. Thus, third plunger 54 will abut the wall and is sized such
that there is provided an inlet 125 and an outlet 127 from shearing channel122. When
the mixing flow is reversed, the mixture enters outlet 127 and exits inlet 125.
In addition to the embodiment described above, alternate
embodiments are contemplated. For example, a plunger need not be used as a means
for forcing flow or mixing of compositions held within. Therefore, as one skilled in
the art would appreciate, other embodiment use other types of mechanisms to cause a
composition to flow out of or into a compartment. For example, in an alternative
embodiment, the walls of the conduit are compressed, causing the available volume in
a compartment to decrease, and thus causing a composition contained within to flow
out of the compartment. Accordingly, if the walls of the conduit are expanded
outward, causing the internal volume to increase and creating a relative lower
pressure, composition contained elsewhere in the device is forced to flow into the
compartment. In such case, the conduct is made of a flexible and durable plastic.
Alternatively, the compartment has walls that are separate from the
conduit, and in such case, the compartment is a distinct chamber. For the purposes of
this disclosure, compartment and chamber may be used interchangeably to describe
various embodiments.
In one embodiment, the conduit and or the chambers that form the
areas for mixing is at least one removable and disposable component of the device.
These components, which include chambers, plungers, shearing channels, or other
components described herein, are be pre-filled with the desired compositions for
mixing and administration. Therefore, in one embodiment, the device is reusable and
chambers with compositions are in the form of disposable cartridges. Active
ingredients and other compositions to the final pharmaceutical composition are stored
in one or more pre-packaged cartridges. As noted above, such cartridges serve as
chambers themselves or be inserted into chambers in certain embodiments. In such an
embodiment, plungers, conduits, and other components for mixing are part of the one
or more disposable cartridges.
When a composition is a chamber in subject to settling or separation,
pre-mixing in a single chamber prior to combining the composition with the other
chambers is desired. In such a case, as one skilled in the art would appreciate,
alternative embodiments use different means of mixing, such as one of the means
described herein.
Although the embodiment illustrated in the figures includes
compartments shown as being separated by a plunger, alternative embodiments use
different means of separation, such as a door, wall, or permeable membrane. In the
case of a wall, one embodiment includes a separation device in the shearing channel,
which opens for mixing. In some embodiments, more than one conduit is used. One
such embodiment uses two conduits to mix two compositions separately, which are
then combined prior to or at the time of dispensing. In an alternative embodiment, the
two conduits are dispensed through separate openings in the device or through the
same opening but in separate steps, in which case the administration is sequential.
The coil spring, illustrated and described herein, is not the only
contemplated embodiment. Other mechanical (including electronically powered)
components are used to facilitate mixing in alternative embodiments. For example,
one embodiment has a mechanical crank or motor. In an embodiment containing a
motor, a battery is used; it should be noted, however, that a motor need not be present
in the device for a battery to be included. A battery is desired for some embodiments
because it allows for additional components to be included in the device.
Contemplated components include: sensors to measure the
temperature, pH, viscosity, and/or other physical and chemical properties; external
electronic displays; heating and/or cooling component(s); microprocessors,
transmitters, and other electrical components; and/or values.
A heating or cooling component provides for two additional utilities.
First, in one embodiment, the heating and/or cooling component aids in the storage of
a composition in at least one chamber by providing temperature modification,
notification, and/or control. Second, in another embodiment or combined with the
previous embodiment, the heating and/or cooling component is used as a
thermodynamic catalyst for reactions in one or more chambers. In one embodiment,
the heating and/or cooling component is electrically powered or chemically facilitated.
In one embodiment, one or more valves is desired or necessary to achieve a desired
result because of changes in pressure before, during, or after the mixing of one or
more compositions. In one embodiment, such a valve is a one way valve, capable of
releasing gases resulting from mixing.
In some embodiments, compositions are stored at a pressure above
or below atmospheric pressure. In one embodiment, one or more chambers fill with
air. In other embodiments, one or more chambers contain a gas at above atmospheric
pressure or below atmospheric pressure.
The second plunger need not be the only means of blocking passage
through the shearing channel prior to activation by a user. In an alternative
embodiment, , the wall of the conduit has a door that is connected to the compression
systems, the plungers and springs for example, that simultaneously opens the shearing
channel upon initiation by a device user. In addition, in some embodiments, a third
composition is stored in the shearing channel. As one skilled in the art would
appreciate, one embodiment contains a shearing channel where the mixing means is
one or a combination means of mixing, depending on the desired result. For example,
the shearing channel may create vortex flow or utilize baffles and other protruding
m1xmg members. In another example, the shearing channel is replaced by other
mixing means. In one embodiment for example, the third plunger, which separated
as to open a passage
the two compartments in the illustrated embodiment, operates
way for exchange of compositions stored in the two compartments; for instance, the
third plunger pivots open upon activation of mixing by a user. In one embodiment,
the disclosed device allows for high shear flow for efficient emulsification of
components with a minimum or exact number of mixing cycles. Although high shear
flow is desired in some instances, low shear flow may be desired. In such situations,
another embodiment includes at least one shearing channel that is enlarged or a less
shearing mixing means is used.
Depending on the compositions being mixed, the number of cycles
varies in alternate embodiments. In order to ensure a proper number of cycles, in
some embodiments, the device includes a cycle counter and/or a component to limit
the number of cycles possible for a given administration of a dosage. In an
embodiment, a cycle counter includes a mechanical wheel or crank and the counter is
internal with a stopping mechanism and/or contains an external readable display for
the user. A component to count and/or limit the number of cycles is mechanical in
one embodiment and electrical in another.
In an alternative embodiment, the upper housing is a disposable
component and the lower housing is component made for repeated use. Therefore, in
one embodiment, the lower housing component is the location for features such as the
cycle counter, temperature monitor, battery, and other features discussed in and
foreseeable from this disclosure.
In some embodiments, after a pre-determined number of cycles, a
composition in a third chamber is released into the chamber(s) where mixing is
occurring. More than three chambers is used in this manner in other embodiments.
Therefore, where sequential reactions of multiple components are require or desired
for a final composition, the device and method can achieve the desired result. In one
embodiment for example, a first composition is stored in a first chamber, a second
composition is stored in a second chamber, and a third composition is then stored in a
third chamber. Upon initiation of mixing the first and second compositions are
combined for a desired number of mixing cycles. Next, the third composition in the
third chamber is combined with the already mixed first composition and second
composition. This example is useful for a reaction where initial compound in the first
and second compositions cause adverse reactions with the compounds in the third
composition. However, upon mixing the first and second compositions, the undesired
components are chemically altered via chemical reaction and therefore, no adverse
reaction occurs when the third composition is mixed with the first two. In alternative
embodiments, it is desired to have the product of the reaction of the first and second
compositions at equilibrium prior to mixing and reacting the product with the third
composition.
Because of the area of application in some instances, one
embodiment includes a throttle or regulator for limiting the rate at which the
composition can be dispensed from the device. For example, one embodiment is for
the treatment of male sexual dysfunction calls for application of the pharmaceutical
composition in the urethra. Therefore, dispensing the pharmaceutical composition at a
high rate may result in a less then desired amount of pharmaceutical composition
entering and penetrating the urethra due to splatter and/or off-target application.
In an alternative embodiment, the amount in one or more chambers
that is mixed and/or dispensed can be set and/or calibrated. For example, one
embodiment includes 300 meg of alprostadil in 100 mg of cream. However, in some
cases, it is desirable to titrate the dosage down to 200 meg of alprostadil. In addition,
a patient sometimes finds that the most effective and/or most tolerated dosage is
somewhere between 300 meg and 200 meg of alprostadil. In this embodiment, the
composition containing the active ingredient, alprostadil, is stored in the first chamber,
a third chamber, and a fourth chamber. A different composition containing inactive
ingredients is stored in the second chamber. In such an embodiment, the combined
volume of all chambers is between 1 mL and 2 mL. Therefore, the first chamber
contains 200 meg of alprostadil and the third and fourth chambers each contain 50
meg of alprostadil. In an alternative embodiment, there are only three chambers,
whereby the third chamber contains 100 meg of alprostadil. The sum of all chambers
results in total of 300 meg of alprostadil. In the device, the contents are mixed in the
first chamber and second chamber. The contents of the third chamber and fourth
chamber are added to the first chamber or second chamber if selected to be included in
the final pharmaceutical product to be dispensed, which depends on the desired
dosage.
For example, prior to mixing, the subject determines whether a dose
of 200 meg, 250 meg, or 300 meg is desired. If the subject desires to administer a
dose of 250 meg, the contents of either the third chamber or the fourth chamber are
mixed with the first chamber and the second chamber. This mixing selection is
controlled by the either mechanical or electrical components on the device; for
example, the user presses an external button on the device that sets the third chamber
to be mixed with the first and second chambers. Then upon mixing initiation by the
user, contents of the three chambers are mixed and dispensed as a dosage of 250 meg
in one of the manners described in this disclosure.
In some embodiments, the device contains one or more components
for more exact mixing. For example, hand actuated plungers, such as those disclosed
in U.S. Patent No. 4,250,755 (Kenney), are used to allow for more exact dosages.
Other actuating components, electronic for example, are also contemplated and
desired for other embodiments. Furthermore, more precise actuating plungers are
used in the dispensing of the composition other embodiments.
In one embodiment, the device is built as one assembly; therefore,
the upper and lower housing element is not separated for dispensing because there is
no second housing to be separated. Instead, there is an opening that can be opened at
the time for dispensing. The body and components of the device are made utilizing
molding or other fabrication techniques. In one embodiment, materials for such
components 1s rigid plastic, such as polyolefin, including polyethylene,
polypropylene, and the like, suitable for injection molding, and in some embodiments
the plastics are clear, translucent or opaque. In the case of clear or translucent
material, compositions that are subject to color change or physical property change
due to spoilage is viewable by a user.
In addition to flexibility m the dimensions of the device, some
embodiments of the device are designed for better application, and included additional
components such as nozzles or adapters. Such nozzles or adapter are be suitable for
delivery of the pharmaceutical composition onto or into the body, including the
urethra, the vagina, the ear and the eye, the mouth, but delivery is not limited to those
parts expressly listed here. In one such embodiment, the device includes a suitable
conical nozzle for administration of a pharmaceutical composition for the treatment of
male sexual dysfunction into the urethra of a subject. In another embodiment, the
device includes a suitable conical nozzle for administration of a pharmaceutical
composition for the treatment of female sexual dysfunction into the vagina of a
subject.
In one embodiment, the device and composition are provided in a
kit. In another embodiment, the kit includes additional components. For example, for
the use of treating male sexual dysfunction, the kit comprises a pharmaceutical
composition for treatment of erectile dysfunction, an applicator, and a contraceptive
device (such as a condom). A condom is a desired kit accessory because in the case
where alprostadil is used for the treatment of male sexual dysfunction, it is advisable
for the male subject to use a condom when sexual intercourse is planned or takes place
with a pregnant or lactating woman because the effects of alprostadil on women is not
well studied.
As one skilled in the art would appreciate, the present device and
components thereof can be made with nearly any dimensions, constructions, and
materials suitable to practice the details of this disclosure and achieve the desired
results.
METHODS OF TREATMENT.
In one embodiment, methods are used to administer a pharmaceutical
composition. Where embodiments are used for the administration of a pharmaceutical
application, such application includes, but is not limited to, delivery of medicament to
the urethra and urethral meatus for male sexual dysfunction; direct vaginal and/or
clitoral application for female sexual dysfunction; intraoral application of a vaccine or
oral care product; intranasal application of a vaccine or medicament; intra-aural
application; or ophthalmic application of a medicament.
In another embodiment, the methods are used to prepare and
administer a pharmaceutical composition. In some embodiments, pharmaceutical
compositions include an effective amount of an active ingredient and at least one other
compound. However, as previously noted, the applications and methods of this
disclosure not limit to pharmaceutical products. Hence, the methods herein can be
used for vitamins, beauty products, foods, and the like.
Suitable formulations for mixing and administration include for
example, creams, ointments, lotions, gels, semi-solids, spray-aerosols, oils, aqueous
solutions, oil-in-water or water-in-oil emulsions, ointments, pastes, and solutions or
suspensiOns. The specific compounds of a composition to be used, as will be
appreciated by those skilled in the art, is one that provides for optimum drug delivery
and effectiveness of the active ingredient or ingredients. For some methods,
formulations for topical administration further comprise one or more of the additional
ingredients as described herein. The compounds may be acid or base. Thickeners,
preservatives, lubricants, penetration enhancers, excipients, suspending agents, and
other non-active ingredients are included in alternative embodiments, as one skilled in
the art would appreciate. In some embodiments, it is required that the compositions,
components, and/or the device be sterilize.
In one embodiment, the pharmaceutical composition is stored in the
device in more than one chamber. However, in some embodiments, only one chamber
is used for storage. In one embodiment, one compartment contains a vasoactive agent,
and an at least second compartment contains a diluent composition. When combined
in the device, these at least two composition are mixed to form a pharmaceutical
composition. The storing of the compositions in separate compartments prior to
mixing increases the shelf-life of the compositions and prevents time-caused
degradation of the pharmaceutical composition. Pharmaceutical compositions for
alternative embodiments are disclosed in U.S. Pat. No. 7,560,489 (Frank et al.). One
such composition comprises a pharmaceutically acceptable excipient and a
prostaglandin, such as prostaglandin El (alprostadil), in the amount of 200 meg or 300
meg in 100 mg of cream. Other pharmaceutical compositions include, but are not
limited to those compositions disclosed in U.S. Pat. No 6,486,207 (Yeager et al.), U.S.
2002/0045665 Al (Yeager et al.), and U.S. 2004/0241245 Al (Lu et al.).
Routes of administration include, but are not limited to transdermal,
intranasal, buccal, or rectal. In one embodiments, the route of administration is
topical and transdermal. However, in some embodiment, the device is used to deliver
compositions orally, as an aerosol, or liquid for example. Another example includes
administration to a subject's eye, where the pharmaceutical composition is mixed
immediately prior and then administered on the eye of the subject. In one
embodiment, the disease for treatment is sexual dysfunction, which includes male
sexual dysfunction and female sexual dysfunction.
In the treatment of female sexual dysfunction, namely female sexual
arousal disorder, alprostadil acts directly on local tissues to produce increases in
vaginal secretion, increases in vaginal engorgement, and acts indirectly on the central
nervous system to increase sexual responsiveness and arousal.
In one embodiment for the treatment of female sexual dysfunction, at
least 0.5 mg to lOmg of the active ingredient, such as alprostadil, is topically
administered. In some embodiments, compositions contain between 0.05% a 0.4%
alprostadil. In such case, the pharmaceutical product is applied to the labia, clitoris
and/or the vulvar region of the vagina. Optionally, the reconstitution device includes
a modified applicator tip for administration in such region.
For the treatment of male sexual dysfunction, a method of treatment
includes application of the pharmaceutical composition in the proximal fossa
navicularis and the distal portion of the penile urethra proper. The high glycogen
content and bacterial flora within the fossa navicularis provides a naturally lower pH
within the space, so that lower pH compositions that provide for high solubility of
alprostadil can be more easily tolerated without excess irritation of the tissues.
In the treatment of a disease, such as those mentioned above, it is
sometimes necessary to pre-treat and/or post-treat an area of application, namely in
transdermal administration. As mentioned above, alprostadil has a higher solubility at
a lower pH. Therefore, lowering the pH of an application area with a pre-treatment
and bringing the pH to a more natural level with a post-treatment is advantageous and
desirable.
In one embodiment, a pre-treatment step is included, in which the
area of application for the pharmaceutical composition is first contacted with a
composition for pre-treating or preparation the area of application. By adding a pre
treatment step immediately before administering the pharmaceutical composition,
absorption can be increased or decreased, which can allow for more control of the
drug interaction and produce a more desired result. Possible pre-treatment methods
include increasing or decreasing the temperature at the application area, sterilizing the
application site, lowering or raising the pH, soaking the application site, which in
some embodiments is a subject's tissue (Grasso & Lansdown, Methods ofmeasuring,
and factors affecting, percutaneous absorbtion, J. Soc. COSMET. CHEM. 23, 484-509).
In another embodiment, a post-treatment step is included.
Furthermore, embodiments include one or more pre-treatment steps and one or more
post-treatment steps. The post-treatment is an important step in reducing side effects,
namely skin irritation in the case of topical application. Therefore, application of a
post-treatment immediately after administration of a pharmaceutical composition
typically decreases undesired effects.
For example, to combat side-effects of burning sensations or skin
irritation, any of the following steps are taken: applying a topical vitamin E
formulation (Nachbar & Korting, The role ofvitamin E in normal and damaged skin,
J. MOL. MED. 73:7-17 (1995)); rinsing the affected area with a basic soap and room
temperature or cooler water to neutralize the pH, restore the area to ambient
temperatures and dilute remaining drug compound (Grasso & Lansdown, Methods of
measuring, and factors affecting, percutaneous absorbtion, J. Soc. COSMET. CHEM.
23, 484-509); application of topical immunosuppressant, such as hydrocortisone, to
affected area; application of a topical analgesic, such as menthol, to the affected area
(Galeotti et al, Menthol: a natural analgesic compound, Neuroscience Letters 322,
3:145-148 (April2002)).
In some embodiments, the post-treatment is for sites or locations
other than the pharmaceutical drug composition application site. For example, a
common effect of alprostadil is irritation to skin, including hands. A subject who
applies alprostadil for the treatment of sexual dysfunction must wash his or her hands
after application to prevent irritation to his or her hands. Therefore, combining the
pharmaceutical composition for treatment of sexual dysfunction and a post-application
cleansing composition or object is desirable. In some embodiments, the post
application may be in the form of a moist tissue, which includes one or more
compositions for treating irritation.
In one embodiment, the device includes a separate chamber and a
separate dispenser for dispensing an anti-irritant cream. Examples of anti-irritants
include but are not limited to: glycerin esters of fatty acids such as mono- or tri
glycerides of fatty acids, including their polyethylene glycol complex, polyethylene
glycol or propylene glycol esters of fatty acids or vegetable oils; vegetable oils,
including their hydrogenated form, such as sesame oil, soybean oil, castor oil, corn oil,
palm oil, peanut oil, cacao oil, cotton seed oil, sunflower seed oil, safflower oil,
almond oil or olive oil; fatty acids and fatty alcohols, and their esters, such as oleic
acid, linolenic acid, linoleic acid, palmitic acid, palmitoleic acid, arachidonic acid,
myristic acid, capric acid, caprylic acid, lauric acid, stearic acid, lauryl alcohol, oleyl
alcohol, cetyl alcohol, stearyl alcohol, ethyl oleate, oleyl laurate, isopropyl myristate,
isopropyl palmitate, 2-octyldodecyl myristate or cetyl palmitate; and a mixture
thereof.
In another embodiment, for the treatment of nail fungus, the
compositions to be applied include two part formulation that is sequentially applied,
as described in U.S. Pat. No. 7,462,362 (Kepda et al.). In such an embodiment, the
first part is a composition for quick penetration comprising an active ingredient, such
as terbinafine and pharmaceutically acceptable carrier. The second part is a
composition to act as a protective barrier, comprising additional active ingredient for
gradual penetration, an effective amount of film-forming polymer, and a
pharmaceutically acceptable carrier.
In some embodiments, it is necessary for time passage between
administration of a first product and administration of a second product.
As one skilled in the art would appreciate, the present device and
components thereof can be made with nearly any dimensions, constructions, and
materials suitable to practice the details of this disclosure and achieve the desired
results.
EXAMPLE 1: DEVICE AND METHOD OF TREATMENT OF MALE SEXUAL
DYSFUNCTION
In one embodiment for the treatment of male sexual dysfunction, two
separate components of a pharmaceutically acceptable compound for the treatment of
male sexual dysfunction are stored separately and mixed immediately prior to
administration. In this embodiment, a reconstitution device stores, mixes, and applies
the final composition. The device is constructed out of plastic and comprises an upper
housing and lower housing. The conduit inside the upper housing forms two
compartments. The first chamber and second chamber are designed according to the
embodiment illustrated in FIG 3-FIG 9.
The first compartment includes an effective amount of the active
ingredient, alprostadil in this example, and a diluent. The second compartment
includes a pharmaceutically acceptable penetration enhancer, DDAIP.HCl (dodecyl
N,N-dimethylaminopropionate hydrochloride) in this example. The total volume of
the combined compositions is approximately 1 cc.
The device is made for one time use; therefore, the compositions
contained in the device are put into the respective compartments prior to a subject
being giving the device.
This example contains a method of storing and mixing, whereby the
two separate compositions are stored separately until mixing immediately prior to
administration. Since the compositions are stable at room temperature when stored in
separate compartments, there is generally no need to refrigerate the device and
compositions. The compositions are then mixed immediately prior to application,
which results in minimal degradation of the final pharmaceutical composition. In this
example, the compositions of the two chambers are mixed thirty seconds prior to
administration of the mixed composition, comprises is an effective amount of
alprostadil for the treatment of sexual dysfunction. This example contains a method
of treatment, where the male subject mixes the compositions immediately prior to
administration and administered the composition to the urethra of the subject.
When a subject, who is typically the device user, desires to apply the
on the top of the device, where the
pharmaceutical treatment, the subject presses down
surface of the plunger head is exposed to the external environment. Upon the user
pushing down on the plunger head, the plunger is released from a locked position
between two projections.
After being released from the locked position, the subject agam
applies downward pressure on the plunger head, which in turn engages the mixing
components of the device. This pressure on the plunger rod causes movement of the
second plunger and third plunger, thereby creating flow though the shearing channel
and between the two chambers.
After the desired number of mixing cycles, four in this example, the
upper housing and lower housing are separated and the mixture is exposed for use.
The subject then dispenses the composition onto the subject's urethra.
EXAMPLE 2: DEVICE AND METHOD FOR TREATMENT OF NAIL FUNGUS
In one embodiment for the treatment of nail fungus, two separate
pharmaceutical products are used and are administered sequentially. Furthermore, the
pharmaceutical products are to be administered multiple times throughout the course
of treatment.
In this embodiment, a reconstitution device stores, mixes, and
applies the pharmaceutical products. The device is constructed out of plastic, has a
upper housing and lower housing, two conduits, and one dispensing end.
The conduit inside the upper housing forms two compartments. The
first chamber and second chamber are designed according to the embodiment
illustrated in FIG 3-FIG 9.
The two compartments part of a cartridge. A first compartment
includes a first composition comprising terbinafine and a pharmaceutically acceptable
earner. A second compartment includes a second composition comprising terbinafine,
a film-forming polymer, and a pharmaceutically acceptable carrier.
The two compartments each contain two sub-compartments. In the
first compartment, the first sub-compartment contains terbinafine in a diluent, and the
second sub-compartment contains the pharmaceutically acceptable carrier. In the
second compartment, the first sub-compartment contains terbinafine in a diluent, and
the second sub-compartment contains the pharmaceutically acceptable carrier and a
film-forming polymer.
The device and methods described herein may be combined with any
suitable compositions and/or instructions for operation. It will be understood that the
above described embodiment is for purposes of illustration only and that changes and
modifications may be made thereto without departing from the spirit and scope of the
invention.
I/WE
Claims (14)
1. A method of mixing comprising: filling a device with at least two compositions, wherein a first composition of said at least two compositions is a vasoactive agent; storing said at least two compositions; and mixing said at least two compositions with said device wherein said device comprises: at least one housing element capable of containing at least two compositions; and at least one dispensing assembly for mixing said at least two compositions, the at least one dispensing assembly comprising a spring member.
2. The method of claim 1, wherein the device further comprises a nozzle, a temperature changing element or at least one valve.
3. The method of claim 1, wherein said at least one housing element comprises at least one compressible compartment, and wherein a compression of the at least one compressible compartment results in flow of said at least one composition and wherein at least one compartment contains a gas.
4. The method of claim 1, wherein said device is for use of a single dispensing of a mixed composition or wherein said device is for more than one use for dispensing of a mixed composition contained in an at least one chamber.
5. The method of claim 1, wherein said at least one dispensing assembly comprises a first chamber and a second chamber; said first chamber being associated with a first mixing element and said second chamber being associated with a second mixing element; and a first composition in said first chamber is mixed by said first mixing element prior to said first composition being mixed with a second composition contained within said second chamber; or wherein the at least one dispensing assembly comprises a membrane and said membrane separate a first compartment and a second compartment, and wherein a first sensor measures temperature, pH or viscosity of at least one composition. AH26(12548509_1):KEH
6. The method of claim 1, wherein said device comprises: a first dispensing assembly further comprising at least one first dispensing assembly compartment; and a second dispensing assembly further comprising at least one second dispensing assembly compartment.
7. The method of any one of claims 1 to 6, wherein said at least two compositions are mixed immediately prior to dispensing said at least two compositions and wherein said at least two compositions are mixed with a shearing channel.
8. The method of any one of claims 1 to 7, wherein the temperature of said at least two compositions is changed immediately prior to administration.
9. The method of any one of claims 1 to 6, wherein said at least two compositions form a pharmaceutical composition and wherein said at least two compositions are mixed in a predetermined amount and wherein an actuator is used to select the amount of a least one composition of said at least two compositions.
10. The method of claim 9, wherein the pharmaceutical composition is a pharmaceutically acceptable composition.
11. The method of claim 1, wherein the vasoactive agent is alprostadil.
12. The method of any one of claims 1 to 11, wherein the first composition of said at least two compositions is a vasoactive agent, such as alprostadil, for example in an amount between approximately 100 mcg and 400 mcg.
13. The method of any one of claims 1 to 6, wherein a first composition of said at least two compositions is stored in a first compartment and a second composition of said at least two compositions is stored in a second compartment prior to mixing, or wherein the said at least two compositions are stored in at least three compartments and an effective dosage of a pharmaceutical composition is selected by a device user who selects which said at least two compositions are mixed. AH26(12548509_1):KEH
14. The method of any one of claims 1 to 6, wherein said at least two compositions comprise at least three compositions, whereby a first composition and second composition are mixed within said device, and subsequently, a third composition is mixed with said first composition and said second composition. Nexmed Holdings, Inc. By the Attorneys for the Applicant SPRUSON & FERGUSON Per: AH26(12548509_1):KEH
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
NZ715742A NZ715742B2 (en) | 2012-07-06 | Reconstitution methods |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA2745320A CA2745320A1 (en) | 2011-07-06 | 2011-07-06 | Reconstitution device |
NZ618749A NZ618749B2 (en) | 2012-07-06 | Reconstitution method | |
NZ715742A NZ715742B2 (en) | 2012-07-06 | Reconstitution methods |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ715742A NZ715742A (en) | 2017-07-28 |
NZ715742B2 true NZ715742B2 (en) | 2017-10-31 |
Family
ID=
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2016277575A1 (en) | Reconstitution device | |
AU2007343579B2 (en) | Spreading implement | |
AU782251B2 (en) | Tissue sensitizing compounds for females with methods and apparatus for the delivery of these compounds | |
US20150164736A1 (en) | Lubrication applicator for body lumen | |
CN114585410A (en) | Intraurethral drug dosage form and device | |
NZ715742B2 (en) | Reconstitution methods | |
US20230055051A1 (en) | An earplug for administering a fluid agent into an ear canal | |
TW201402125A (en) | Reconstitution device | |
CA3013821C (en) | Nasal treatment delivery device with carbon dioxide and saline, and methods, including low flow rates | |
CN105878017A (en) | Redissolution method and redissolution device | |
Damodharan | Dosage Forms Unit I | |
NZ619048B2 (en) | Reconstitution device |