CN101068589B - 经皮给予活性物质的装置 - Google Patents
经皮给予活性物质的装置 Download PDFInfo
- Publication number
- CN101068589B CN101068589B CN2004800338811A CN200480033881A CN101068589B CN 101068589 B CN101068589 B CN 101068589B CN 2004800338811 A CN2004800338811 A CN 2004800338811A CN 200480033881 A CN200480033881 A CN 200480033881A CN 101068589 B CN101068589 B CN 101068589B
- Authority
- CN
- China
- Prior art keywords
- microprojection
- skin
- active substance
- storage storehouse
- oligonucleotide
- 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.)
- Expired - Fee Related
Links
- 239000004480 active ingredient Substances 0.000 title claims description 7
- 239000013543 active substance Substances 0.000 claims abstract description 54
- 230000000149 penetrating effect Effects 0.000 claims abstract description 3
- 229920000642 polymer Polymers 0.000 claims description 13
- 239000011159 matrix material Substances 0.000 claims description 8
- 108091034117 Oligonucleotide Proteins 0.000 claims description 7
- 239000000758 substrate Substances 0.000 claims description 7
- 239000012752 auxiliary agent Substances 0.000 claims description 6
- 108091033319 polynucleotide Proteins 0.000 claims description 6
- 102000040430 polynucleotide Human genes 0.000 claims description 6
- 239000002157 polynucleotide Substances 0.000 claims description 6
- 229960005486 vaccine Drugs 0.000 claims description 5
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 230000000844 anti-bacterial effect Effects 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 238000010353 genetic engineering Methods 0.000 claims 1
- 210000003491 skin Anatomy 0.000 description 47
- 239000010410 layer Substances 0.000 description 23
- -1 politef Polymers 0.000 description 12
- 230000004888 barrier function Effects 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 6
- 239000004820 Pressure-sensitive adhesive Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000010408 film Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 238000009792 diffusion process Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 229920003023 plastic Polymers 0.000 description 3
- 239000004033 plastic Substances 0.000 description 3
- 239000004800 polyvinyl chloride Substances 0.000 description 3
- 229920000915 polyvinyl chloride Polymers 0.000 description 3
- 229910000838 Al alloy Inorganic materials 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 239000002955 immunomodulating agent Substances 0.000 description 2
- 229940121354 immunomodulator Drugs 0.000 description 2
- 230000002584 immunomodulator Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000033001 locomotion Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 229950000845 politef Drugs 0.000 description 2
- 229920001707 polybutylene terephthalate Polymers 0.000 description 2
- 229920000346 polystyrene-polyisoprene block-polystyrene Polymers 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 230000002048 spasmolytic effect Effects 0.000 description 2
- 229920000468 styrene butadiene styrene block copolymer Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 102000015554 Dopamine receptor Human genes 0.000 description 1
- 108050004812 Dopamine receptor Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 239000004831 Hot glue Substances 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 101150064138 MAP1 gene Proteins 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 229940087098 Oxidase inhibitor Drugs 0.000 description 1
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 1
- 101800000989 Oxytocin Proteins 0.000 description 1
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002367 Polyisobutene Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 239000004902 Softening Agent Substances 0.000 description 1
- 102000013275 Somatomedins Human genes 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 229910001069 Ti alloy Inorganic materials 0.000 description 1
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 230000003555 analeptic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 230000002686 anti-diuretic effect Effects 0.000 description 1
- 229940046836 anti-estrogen Drugs 0.000 description 1
- 230000001833 anti-estrogenic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000002460 anti-migrenic effect Effects 0.000 description 1
- 230000000648 anti-parkinson Effects 0.000 description 1
- 230000003356 anti-rheumatic effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 229940125713 antianxiety drug Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940124538 antidiuretic agent Drugs 0.000 description 1
- 239000003160 antidiuretic agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000000939 antiparkinson agent Substances 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940127243 cholinergic drug Drugs 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 210000000736 corneocyte Anatomy 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 238000005530 etching Methods 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 229920002457 flexible plastic Polymers 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000007769 metal material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 1
- 229960001723 oxytocin Drugs 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920006267 polyester film Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000013047 polymeric layer Substances 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 150000003097 polyterpenes Chemical class 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- 229920003051 synthetic elastomer Polymers 0.000 description 1
- 239000005061 synthetic rubber Substances 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940125725 tranquilizer Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
Images
Classifications
-
- 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
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
-
- 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
- A61K9/0021—Intradermal administration, e.g. through microneedle arrays, needleless injectors
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- 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
- A61M37/0015—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles
- A61M2037/003—Other apparatus for introducing media into the body; Percutany, i.e. introducing medicines into the body by diffusion through the skin by using microneedles having a lumen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/20—Applying electric currents by contact electrodes continuous direct currents
- A61N1/30—Apparatus for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body, or cataphoresis
- A61N1/303—Constructional details
Landscapes
- Health & Medical Sciences (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Medical Informatics (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
一种用于经皮给予活性物质的装置，包括背衬层和与其连接的含有活性物质的贮库，其特征在于所述装置的面向皮肤的接触面具有多个微突出物，该微突出物适于穿入皮肤并有使该突出物难于从皮肤中拔出的结构。
Description
技术领域
本发明涉及能经皮给予活性物质的装置。本发明进一步涉及这种经皮给予活性物质或助剂的装置的用途。
背景技术
经皮治疗系统目前已被广泛用作治疗各种疾病的给药剂型。用这项技术，特别是活性物质尼古丁、硝酸甘油、东莨菪碱和雌二醇，而且许多更新的活性物质可以以控制的和暂时延长的方式发挥作用。当使用这种给药剂型时，对于大量活性物质，可以很大程度地抑制口服给药的情况下经常出现的生理首过效应，在这一点上该给药剂型具有特别的优势。这最终使更大量的活性物质能够到达其作用部位。
通常，经皮治疗系统(TTS)以以下方式构成，它们包括压敏粘合活性物质贮库或在任何情况下存在至少一种压敏胶层，以用于将该系统粘附到皮肤上。该系统和皮肤之间的粘合键是由所用的聚合物的自粘特性或由聚合物和助剂的适当的混合物产生的。
但是，只由表面张力现象造成的压敏胶在皮肤上的粘附不总是牢固的。由于这个原因，经常观察到关于TTS的粘附问题。不充分的粘附主要影响最长应用周期；通常，这种系统在皮肤上的可用性被限制到最长约7天。
用TTS释放活性物质通常通过活性物质经TTS的含聚合物层和软塑料层的扩散实现，在这种情况下，活性物质通过TTS的皮肤接触侧到达皮肤的表面。接下来，活性物质分子最初通过最外面的皮肤层(角质层)扩散，然后到达表皮较深的地方，在那里它们转移进入血液循环。
但是，只对于非常少量的活性物质，前述的活性物质的扩散转运才会以足以达到治疗目的速度发生。这主要是由角质层的天然屏障作用引起的。这种屏障作用使高分子活性物质(如肽、蛋白质、寡核苷酸和多核苷酸)或强极性活性物质的经皮给药显著地更加困难，或不可能。
所以，已有很多通过采用适当的方法克服角质层的屏障性质的尝试。例如，这可以通过采用化学渗透促进剂(如乙醇或其它醇)，电压差(如离子导入技术)，或甚至通过机械改性角质层而实现。为此，根据US 6334856，可以使用具有在一范围内布置的多个空心微针的装置。这些针确实具有非常尖的外形，但它们只穿入皮肤几百微米深。尽管这能够实现含有活性物质的液体的给药同时避免角质层的屏障性质，但是在很多情况下其不能提供液体形式的活性物质。其原因可能是，例如活性物质溶解度不够或活性物质溶液的稳定性不够。此外，由于可通过这些微针施用的液体体积很小，所以可施用的活性物质的量非常小(在几微克的范围内)。
US 6083196中描述了与US 6334856中所描述的装置非常相似的装置。该装置包括在其上排列有多个可以用于穿透皮肤的微突出物的载体膜。由于这种装置不能粘附到皮肤上，所以通过另外存在的固定装置(如以附加片的形式)的方式将该装置固定到皮肤上。
发明内容
所以，本发明的目的是提供一种经皮给予活性物质的装置，该装置特别适于给予高分子或强极性活性物质，并且其消除或减少了现有技术的上述缺点。更具体而言，本发明因此能够经皮给予不是以液体形式存在的活性物质，而且即使没有额外的自粘方式也能使该装置粘附到皮肤上。
通过根据本发明的装置令人惊奇地达到了这个目的，该装置具有经皮治疗系统的一般特征，具有背衬层和与其连接的含有活性物质的贮库，并且其中面向皮肤的接触表面具有多个适于穿入皮肤的钉形或针形微突出物。这些微突出物具有能使该突出物更难于从皮肤中拔出的结构。
因此根据本发明的装置的微突出物的特征在于，将该微突出物插入皮肤所需的力小于后来从皮肤拔出所需的力。
由于微突出物穿透皮肤，克服了角质层的屏障，并且贮库中所含的活性物质从贮库扩散到所述装置的皮肤接触侧后，通过避开所述屏障而能够达到表皮较深的地方。根据本发明的系统使活性物质能够应用到较深的皮肤层，即那些位于角质层的屏障层之下的皮肤层。
由于上述使微突出物更难于从皮肤中拔出的结构，可以在皮肤上的应用部位固定所述装置，而无需另外的手段来达到这种固定。尽管与粘合键相似，但这是一种基于机械固着的固定。
为了促进穿入皮肤，该微突出物优选指向其末端(即面向皮肤)。它们优选为针形结构且向其末端逐渐变细。如果微突出物的横截面或直径适当小，则即使微突出物不是尖的或逐渐变细的，穿透皮肤也是可能的。微突出物具有基本的圆形、椭圆形、三角形、四边形或多边形、或不规则的横截面。由于非常窄的横截面，用近似具有锯条或锯齿边缘形状的微突出物不可能实现在皮肤上充分的固定，所以应该避免。
微突出物的厚度优选在5～100μm的范围内，特别优选在10～50μm的范围内。对于针形突出物而言，在尖端处的厚度优选为1～10μm，且相对的一端厚度优选为5～100μm。
微突出物的适当长度取决于所述装置的整个厚度、特别是活性物质贮库的厚度，也取决于所需的穿透深度。微突出物的长度优选在50～500μm范围内，特别优选在100～300μm范围内。关于此点，另外优选微突出物从装置的面向皮肤的表面(例如，聚合物基层)突出不到300μm，特别是不到200μm。
上述能使得更难于从皮肤拔出并用于固定装置的结构被布置在突出物的外周线。在个别突出物上也可以存在多个(两个或多个)固定结构，并且它们可以沿着其整个长度分布。但是，至少从装置的皮肤接触侧的表面突出的突出物的区域具有这种结构。
可以通过给微突出物的纵向周线提供底切(undercuts)来实现所述固定结构。特别优选这些结构的外形为阻碍从皮肤拔出的倒钩形。各个微突出物可以具有一个，或优选具有多个这样的倒钩。
根据本发明进一步的实施方案，微突出物或至少其中一部分数量的微突出物以螺旋形状形成并且被旋转布置。通过采用旋转移动，从而可以促进穿入皮肤并且实现在皮肤上的固定。该旋转驱动可以例如以微机械手段、特别以微机械致动器(micromechanical actuator)提供。
通常，所述装置的所有微突出物基本具有相同的形状；然而，本发明也包括其中存在两组或多组不同形状的微突出物的该装置的实施方案。
微突出物的数量优选为1～103/mm2，特别优选10～100/mm2。微突出物与背衬层固定连接，或/和它们被插入和固定于所述装置的含有活性物质的贮库中，该贮库优选为聚合物基质的形式。作为可选择的办法，微突出物可以布置在活性物质渗透膜或层压到活性物质贮库面向皮肤的表面的薄膜上面或里面，从而最好使微突出物的尖端指向外侧，即面向皮肤。所述的膜或薄膜还可以具有压敏粘合特性。
特别地，如果微突出物固定在作为背衬层的半刚性支撑膜上，则具有如下另外的优点，在自发皮肤运动的情况下，由于皮肤的相对运动通过背衬层或支撑膜传递到微突出物，所以引起根据倒钩原理制成的微突出物更深地穿入皮肤。
根据进一步的实施方案，具有倒钩状结构的微突出物还可以具有在面向皮肤一端具有开口的空心针的形式的内部空腔或管道。该空腔或管道与填充液体的贮库相连，空心针被浸入该贮库中或被插入其中。
作为可选择的方法，微突出物还可以由能够使活性物质从贮库通过微突出物扩散到皮肤中的可扩散的材料制成，因此与在空心针的情况下相同，在这种情况下也可以使活性物质直接释放到皮肤中。
微突出物可以由对本领域的技术人员公知的生物相容性和皮肤友好的材料制成，特别是塑料和金属。合适的单独或结合的塑料材料的例子包括：丙烯腈-苯乙烯共聚物、聚甲基丙烯酸甲酯、PVC、聚四氟乙烯、聚酰胺、聚氨酯和聚苯乙烯。合适的金属材料的例子包括：不锈钢、钛和钛合金、铝和铝合金、钴、铬和钼的合金。微突出物可以以对本领域的技术人员公知的方式通过注模法、压模法、加热成型、深冲压、挤压、蚀刻技术等制成。
然而，本发明也包括其中活性物质释放不直接由微突出物实现，而由活性物质贮库面向皮肤的表面实现的实施方案。在这种情况下，微突出物的作用限于穿透皮肤屏障和将装置固定在皮肤上。
根据另一实施方案，所述装置在皮肤侧上具有粘性聚合物基质，其优选与微突出物的平面同延布置。这种方法使装置能够在皮肤上更牢固地固定。在这种情况下，微突出物优选从聚合物基质层的平面突出平均小于300μm，特别优选小于200μm。该粘性聚合物基质可以同时构成活性物质贮库并且包含一种或多种活性物质，任选与一种或多种助剂结合。作为可选择的方法，粘性聚合物基质可以不合有活性物质，活性物质存在于一个或多个另外的层中。
适合作为用于制备所述的聚合物基质、含有活性物质的贮库或压敏胶层的原料具体为以下单独或结合使用的聚合物：聚(甲基)丙烯酸酯、聚异丁烯、多萜、乙烯-乙酸乙烯酯共聚物、合成橡胶、苯乙烯-异戊二烯-苯乙烯嵌段共聚物、苯乙烯-丁二烯-苯乙烯嵌段共聚物、热融粘合剂、橡胶与树脂的混合物、硅氧烷压敏胶、聚乙酸乙烯酯、聚乙烯吡咯烷酮、聚乙烯醇、聚乙二醇、纤维素衍生物(如羟丙基甲基纤维素)。基于上述聚合物的压敏胶组成原则上对本领域的技术人员是公知的。聚合物基质，各个活性物质贮库，可以进一步包含一种或多种已知的助剂，特别选自软化剂、乳化剂、渗透促进剂、增稠剂、增溶剂、稳定剂、填充剂和载体物质的组。
所述的聚合物基质优选具有10～90wt％的聚合物含量，特别优选30～70wt％；助剂的含量优选在0.1～30wt％之间，特别优选在1～10wt％之间。活性物质含量优选在0.1～20wt％的范围内，特别优选在0.5～10wt％的范围内。微突出物的重量百分比在计算中没有考虑。
最为适合作为背衬层或支撑层的是具有特别高强度特征的聚酯膜，例如聚对苯二甲酸乙二醇酯和聚对苯二甲酸丁二醇酯；和另外其它皮肤友好的塑料材料，例如，聚氯乙稀、乙烯乙酸乙烯酯、乙酸乙烯酯、聚乙烯、聚丙烯和纤维素衍生物。
根据本发明的装置面向皮肤的表面优选覆盖有可剥离的保护膜，其可在使用前被剥下。与用于背衬层相同的材料可以用于可剥离保护膜，条件是该层经过适当的表面处理，例如硅化或氟硅化。但是同样也可以使用其它可剥离的保护层，例如聚四氟乙烯处理的纸、玻璃纸、聚氯乙稀等。
根据本发明的装置方便地适于经皮给予用于人或动物的治疗性或预防性处理，也包括用于免疫目的的药学活性物质或疫苗。它们特别适于有效口服剂量(人)小于10mg/天的较高分子或强极性活性物质的给药。
根据本发明的装置特征在于，一方面安全并长时间地粘附到皮肤上；另一方面它们能够经皮给予用别的办法不适于经皮给予的活性物质。
因此这些装置优选包含一种或多种选自肽(特别是肽类激素，例如胰岛素、缩宫素、加压素，生长因子，免疫调节剂、抗生素)、蛋白质(例如酶、干扰素、白细胞介素、抗体)、高活性遗传设计的活性物质、寡核苷酸(如反义寡核苷酸)和多核苷酸(质粒)的组的活性物质，或/和它们包含一种或多种活性疫苗，优选自包括活性细菌、灭活细菌、毒性减弱或遗传改性病毒、灭活病毒、细菌类毒素(bacterial toxoid)、蛋白质、糖蛋白、遗传设计的抗原、及寡核苷酸和多核苷酸的组。
此外，根据本发明的装置还可以用于给予其它药学活性物质。适于这种情况的活性物质特别为选自下面组的那些活性物质：降低或调节血压的物质、作用于心脏的物质(特别是β-阻滞剂和抗心率不齐药物)、止痛剂、类固醇激素、麻醉剂、食欲抑制剂、抗过敏药、抗组胺药、抗动脉硬化活性物质、抗关节炎药/抗风湿药、抗生素、抗胆碱能药、抗惊厥药、抗抑郁药、抗糖尿病剂、止泻药、抗利尿剂、抗雌激素药、抗真菌药/杀真菌活性药、抗真菌活性剂、降脂药、激素、非甾体抗炎药、抗偏头痛药、抗恶心药、抗肿瘤药、抗帕金森药、抗精神病药、解痉药/抗痉挛药、抗血栓药、抗病毒剂、抗焦虑剂、支气管扩张剂、钙通道阻滞剂、胆碱能药物、胆碱酯酶抑制剂、CNS兴奋剂、多巴胺受体激动剂、免疫调节剂、免疫抑制剂、离子交换树脂、单胺氧化酶抑制剂、镇静药/安眠药、溶血栓药、血管扩张药、维生素。
具体实施方式
现在将参照图1～3的示意说明解释本发明。这里说明的实施方案只是作为实施例。
图1和2各显示根据本发明的用于经皮给予活性物质的装置1的纵剖面，该装置处于用于皮肤7的状态。8指插入脂质基质的角状头(corneocytes)。
图1显示具有背衬层或支撑膜2和含有活性物质的聚合物基质3的装置1。在该基质中有多个微突出物4，显示了其中的两个。
微突出物4在它们基本为圆柱形针杆的末端具有穿入皮肤7的尖端6。微突出物4的另一端与背衬层2相连，以使微突出物4与背衬层2的平面近似垂直排列。
微突出物具有倒钩形固定结构5。微突出物的横截面为圆形，固定结构5的横截面也一样。
图2显示图1中描述的装置的修改，其中微突出物4的固定结构5具有螺旋形状。微突出物通过微机械驱动装置(未显示)被旋转式地引导并被旋转。其它的附图标记与图1具有相同的含义。
图3显示(剖面)可以作为驱动装置用于根据本发明的装置中，如根据图2的装置中的微机械致动器。
当微齿条10沿着箭头的一个方向移动时，微齿轮11被驱动。如图2中所示，齿轮的轮轴12可以在它的末端(面向皮肤)区域具有螺旋固定结构。
通过使用多个齿条10和齿轮11，可以实现多个螺旋微突出物4，5的单向驱动。在这种情况下，进一步可以通过相应的一个齿条10同时驱动两个或多个齿轮11。
Claims (15)
1.用于经皮给予活性物质的装置，具有背衬层和与其连接的含有活性物质的贮库，其中，该装置面向皮肤的接触面具有多个针形的微突出物，该微突出物适于穿入皮肤，并且其纵向周线具有一个或多个能够使突出物较难于从皮肤中拔出并使所述的装置固定到皮肤上的底切，其特征在于，所述微突出物被螺旋成形并可旋转地布置，从而在施加旋转时，便于穿入皮肤并实现在皮肤中的固定。
2.根据权利要求1所述的装置，其特征在于所述的微突出物各具有一个或多个倒钩。
3.根据权利要求1所述的装置，其特征在于旋转驱动通过微机械致动器实现。
4.根据权利要求1所述的装置，其特征在于微突出物，或至少几个微突出物，固定在含有活性物质的贮库中。
5.根据权利要求1所述的装置，其特征在于微突出物，或至少几个微突出物，与背衬层相连。
6.根据权利要求1所述的装置，其特征在于微突出物，或至少几个微突出物，形成为空心针。
7.根据权利要求1所述的装置，其特征在于该装置在皮肤侧上具有粘性聚合物基质。
8.根据权利要求7所述的装置，其特征在于所述粘性聚合物基质布置为与微突出物的平面范围相同。
9.根据权利要求7或8所述的装置，其特征在于微突出物从聚合物基质层的平面突出平均不到300μm。
10.根据权利要求7或8所述的装置，其特征在于所述的粘性聚合物基质同时构成活性物质贮库并包含一种或多种活性物质，任选与一种或多种助剂组合。
11.根据权利要求1所述的装置，其特征在于该装置包含选自肽、寡核苷酸和多核苷酸中的一种或多种活性物质。
12.根据权利要求1所述的装置，其特征在于该装置包含选自蛋白质、寡核苷酸和多核苷酸中的一种或多种活性物质。
13.根据权利要求1所述的装置，其特征在于该装置包含一种或多种疫苗。
14.根据权利要求13所述的装置，其特征在于所述疫苗选自细菌、病毒、细菌类毒素、寡核苷酸、多核苷酸中。
15.根据权利要求13或14所述的装置，其特征在于所述疫苗选自遗传工程抗原中。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10353629A DE10353629A1 (de) | 2003-11-17 | 2003-11-17 | Vorrichtung zur transdermalen Verabreichung von Wirkstoffen |
| DE10353629.9 | 2003-11-17 | ||
| PCT/EP2004/012458 WO2005049128A1 (de) | 2003-11-17 | 2004-11-04 | Vorrichtung zur transdermalen verabreichung von wirkstoffen |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101068589A CN101068589A (zh) | 2007-11-07 |
| CN101068589B true CN101068589B (zh) | 2010-05-12 |
Family
ID=34585179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2004800338811A Expired - Fee Related CN101068589B (zh) | 2003-11-17 | 2004-11-04 | 经皮给予活性物质的装置 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20070081977A1 (zh) |
| EP (1) | EP1684846B1 (zh) |
| JP (1) | JP4763612B2 (zh) |
| CN (1) | CN101068589B (zh) |
| AT (1) | ATE389432T1 (zh) |
| CA (1) | CA2546688C (zh) |
| DE (2) | DE10353629A1 (zh) |
| ES (1) | ES2304628T3 (zh) |
| PL (1) | PL1684846T3 (zh) |
| PT (1) | PT1684846E (zh) |
| WO (1) | WO2005049128A1 (zh) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006334991A (ja) * | 2005-06-03 | 2006-12-14 | Univ Kansai | 微細針の射出成形方法 |
| DE102006028987A1 (de) * | 2006-06-24 | 2007-12-27 | Lts Lohmann Therapie-Systeme Ag | Ultraschallverstärktes transdermales therapeutisches System |
| DE102009056746A1 (de) * | 2009-12-04 | 2011-06-09 | Lts Lohmann Therapie-Systeme Ag | Transdermales therapeutisches System für die Verabreichung von Peptiden |
| EP2589408A3 (en) * | 2010-01-29 | 2013-05-29 | Ubiomed Inc. | Micro needle and micro needle apparatus |
| PT2563453T (pt) | 2010-04-28 | 2017-03-15 | Kimberly Clark Co | Dispositivo medicinal possuindo uma nanoforma com melhor interacção celular e um método para a sua formação |
| JP5860032B2 (ja) * | 2010-04-28 | 2016-02-16 | キンバリー クラーク ワールドワイド インコーポレイテッド | 関節リウマチ薬の送達のためのデバイス |
| WO2012046149A1 (en) | 2010-04-28 | 2012-04-12 | Kimberly-Clark Worldwide, Inc. | Method for increasing permeability of an epithelial barrier |
| AU2015271878B2 (en) * | 2010-04-28 | 2017-05-11 | Sorrento Therapeutics, Inc. | Device for delivery of rheumatoid arthritis medication |
| WO2011135531A2 (en) | 2010-04-28 | 2011-11-03 | Kimberly-Clark Worldwide, Inc. | MEDICAL DEVICES FOR DELIVERY OF siRNA |
| HUE058275T2 (hu) | 2011-10-27 | 2022-07-28 | Sorrento Therapeutics Inc | Beültethetõ eszközök biológiailag hatásos szerek tobábbítására |
| KR102265775B1 (ko) | 2011-10-27 | 2021-06-16 | 소렌토 쎄라퓨틱스, 인코포레이티드 | 고점도 생체활성 제제의 경피 전달 방법 |
| US20170246439A9 (en) | 2011-10-27 | 2017-08-31 | Kimberly-Clark Worldwide, Inc. | Increased Bioavailability of Transdermally Delivered Agents |
| CN103203072B (zh) * | 2013-03-25 | 2015-05-20 | 清华大学 | 金属微针阵列柔性贴片、经皮给药器件及经皮给药贴片 |
| ITMI20130586A1 (it) * | 2013-04-11 | 2014-10-12 | Azienda Ospedaliero Universitaria P Isana | Microago e matrice di microaghi per uso medicale, e processo di produzione di detta matrice |
| CN105727438A (zh) * | 2016-04-18 | 2016-07-06 | 朱志飞 | 螺旋微针祛皱装置及祛皱方法 |
| DE102017117784A1 (de) | 2017-08-04 | 2019-02-07 | Lts Lohmann Therapie-Systeme Ag | Applikatorsystem enthaltend ein Mikronadelarray aufweisend einen Wirkstoff für die Wundheilung |
| DE102017118419A1 (de) | 2017-08-11 | 2019-02-14 | Lts Lohmann Therapie-Systeme Ag | Mikronadelarray aufweisend einen Farbumschlag-Indikator |
| BR112020004670A2 (pt) * | 2017-09-12 | 2020-09-15 | Lts Lohmann Therapie-Systeme Ag | dispositivo de microagulhas iontoforético |
| DE102017126501A1 (de) | 2017-11-10 | 2019-05-16 | Lts Lohmann Therapie-Systeme Ag | Mikronadelsystem zur Applikation eines Hepatitis-Impfstoffes |
| EP3723725B1 (de) | 2017-12-14 | 2022-02-02 | LTS LOHMANN Therapie-Systeme AG | Mikronadelarray aufweisend einen wirkstoff in form von salzen |
| EP3735290A2 (en) * | 2018-01-02 | 2020-11-11 | Evonik Corporation | Microneedle delivery system with anchor |
| KR102555433B1 (ko) | 2018-04-19 | 2023-07-13 | 에르테에스 로만 테라피-시스테메 아게 | 인터페론 적용을 위한 마이크로니들 시스템 |
| US11690799B2 (en) | 2018-04-19 | 2023-07-04 | Lts Lohmann Therapie-Systeme Ag | Microneedle system for applying interferon |
| DE102019105694A1 (de) | 2019-03-06 | 2020-09-10 | Lts Lohmann Therapie-Systeme Ag | Mikronadelarray aufweisend ein wärmeerzeugendes Element |
| WO2022115906A1 (en) * | 2020-12-04 | 2022-06-09 | Stefan Mazy | Minimally invasive skin sample collection apparatus |
| DE102021118997A1 (de) | 2021-07-22 | 2023-01-26 | Lts Lohmann Therapie-Systeme Ag. | Mikronadelarray mit Antiseptika |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1204257A (zh) * | 1995-12-09 | 1999-01-06 | 罗曼治疗系统有限责任公司 | 用于皮肤的表面稳定药物制剂 |
| US6334856B1 (en) * | 1998-06-10 | 2002-01-01 | Georgia Tech Research Corporation | Microneedle devices and methods of manufacture and use thereof |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL6614673A (zh) * | 1966-10-18 | 1968-04-19 | ||
| GB1315796A (en) * | 1972-01-29 | 1973-05-02 | Vinnitsky Med I Im Ni Pirogova | Device for intraosseous injection of liquid substrances |
| US4164943A (en) * | 1977-09-30 | 1979-08-21 | Thoratec Laboratories Corporation | Catheter anchor |
| US4890514A (en) * | 1986-06-27 | 1990-01-02 | The J. L. Wickham Co., Inc. | Rotary indexing mechanism |
| US4908213A (en) * | 1989-02-21 | 1990-03-13 | Schering Corporation | Transdermal delivery of nicotine |
| US6048337A (en) * | 1992-01-07 | 2000-04-11 | Principal Ab | Transdermal perfusion of fluids |
| US5562102A (en) * | 1994-11-21 | 1996-10-08 | Taylor; Thomas V. | Multiple biopsy device |
| US5657516A (en) * | 1995-10-12 | 1997-08-19 | Minnesota Mining And Manufacturing Company | Dual structured fastener elements |
| US5730829A (en) * | 1996-03-26 | 1998-03-24 | The Goodyear Tire & Rubber Company | Two drum turret for tire assembly |
| DE69719761T2 (de) * | 1996-06-18 | 2003-12-18 | Alza Corp., Palo Alto | Vorrichtung zur verbesserung der transdermalen verabreichung von medikamenten oder der abnahme von körperflüssigkeiten |
| US6050988A (en) * | 1997-12-11 | 2000-04-18 | Alza Corporation | Device for enhancing transdermal agent flux |
| DE69831268T2 (de) * | 1997-12-11 | 2006-03-09 | Alza Corp., Palo Alto | Vorrichtung zur erhöhung des transdermalen wirkstoffeflusses |
| US7749215B1 (en) * | 1998-02-05 | 2010-07-06 | Biosense, Inc. | Intracardiac cell delivery and cell transplantation |
| EP1086214B1 (en) * | 1998-06-10 | 2009-11-25 | Georgia Tech Research Corporation | Microneedle devices and methods of their manufacture |
| MXPA02004863A (es) * | 1999-11-15 | 2003-01-28 | Velcro Ind | Miembro de sujecion dermica. |
| EP1164404A1 (en) * | 2000-06-14 | 2001-12-19 | Corning Incorporated | An optical switch having an impact printer head actuator |
| US6656147B1 (en) * | 2000-07-17 | 2003-12-02 | Becton, Dickinson And Company | Method and delivery device for the transdermal administration of a substance |
| WO2002094368A1 (en) * | 2000-10-26 | 2002-11-28 | Alza Corporation | Transdermal drug delivery devices having coated microprotrusions |
| US20040106904A1 (en) * | 2002-10-07 | 2004-06-03 | Gonnelli Robert R. | Microneedle array patch |
| EP1633250A2 (en) * | 2003-06-04 | 2006-03-15 | Georgia Tech Research Corporation | Drilling microneedle device |
| US8353861B2 (en) * | 2003-09-18 | 2013-01-15 | Texmac, Inc. | Applicator for applying functional substances into human skin |
-
2003
- 2003-11-17 DE DE10353629A patent/DE10353629A1/de not_active Withdrawn
-
2004
- 2004-11-04 US US10/579,809 patent/US20070081977A1/en not_active Abandoned
- 2004-11-04 JP JP2006538740A patent/JP4763612B2/ja not_active Expired - Fee Related
- 2004-11-04 AT AT04797585T patent/ATE389432T1/de not_active IP Right Cessation
- 2004-11-04 WO PCT/EP2004/012458 patent/WO2005049128A1/de active IP Right Grant
- 2004-11-04 CN CN2004800338811A patent/CN101068589B/zh not_active Expired - Fee Related
- 2004-11-04 DE DE502004006613T patent/DE502004006613D1/de not_active Expired - Lifetime
- 2004-11-04 EP EP04797585A patent/EP1684846B1/de not_active Expired - Lifetime
- 2004-11-04 ES ES04797585T patent/ES2304628T3/es not_active Expired - Lifetime
- 2004-11-04 CA CA2546688A patent/CA2546688C/en not_active Expired - Fee Related
- 2004-11-04 PT PT04797585T patent/PT1684846E/pt unknown
- 2004-11-04 PL PL04797585T patent/PL1684846T3/pl unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1204257A (zh) * | 1995-12-09 | 1999-01-06 | 罗曼治疗系统有限责任公司 | 用于皮肤的表面稳定药物制剂 |
| US6334856B1 (en) * | 1998-06-10 | 2002-01-01 | Georgia Tech Research Corporation | Microneedle devices and methods of manufacture and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| DE10353629A1 (de) | 2005-06-16 |
| JP4763612B2 (ja) | 2011-08-31 |
| CA2546688A1 (en) | 2005-06-02 |
| WO2005049128A1 (de) | 2005-06-02 |
| CA2546688C (en) | 2012-03-13 |
| JP2007520258A (ja) | 2007-07-26 |
| CN101068589A (zh) | 2007-11-07 |
| DE502004006613D1 (de) | 2008-04-30 |
| ATE389432T1 (de) | 2008-04-15 |
| PT1684846E (pt) | 2008-06-25 |
| ES2304628T3 (es) | 2008-10-16 |
| EP1684846B1 (de) | 2008-03-19 |
| US20070081977A1 (en) | 2007-04-12 |
| EP1684846A1 (de) | 2006-08-02 |
| PL1684846T3 (pl) | 2008-08-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101068589B (zh) | 经皮给予活性物质的装置 | |
| US10695547B2 (en) | Microneedle injection apparatus comprising an inverted actuator | |
| US10391290B2 (en) | Microneedle injection apparatus comprising a dual cover | |
| EP2793869B1 (en) | Transdermal adhesive patch assembly with removable microneedle array and method of using same | |
| US9789299B2 (en) | Force-controlled applicator for applying a microneedle device to skin | |
| KR0149492B1 (ko) | 피부 또는 점막에 활성 제제를 투여하기 위한 장치 | |
| US11426571B2 (en) | Microneedle array with composite formulation, and method for manufacturing same | |
| JP2007510445A (ja) | 経皮薬剤送達促進用の前処置法及びシステム | |
| HU206992B (en) | Method for producing transdermal system advantageously plaster suitable for controlled feeding active ingredient | |
| JP2003515555A (ja) | 同一有効成分を含有する貯留部と基質部を備えた経皮投与部材 | |
| Sowmya et al. | Transdermal therapeutic systems—An overview | |
| Anusuya et al. | A Detailed Review on Preparative Methods and Applications of Transdermal Drug Delivery System | |
| Roy et al. | Transdermal Drug Delivery and Organic Polymers: Current Scenario and Future Prospects |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20100512 |