CN1633995A - Percutaneous contraceptive drugs delivery system and method - Google Patents
Percutaneous contraceptive drugs delivery system and method Download PDFInfo
- Publication number
- CN1633995A CN1633995A CN 200410088826 CN200410088826A CN1633995A CN 1633995 A CN1633995 A CN 1633995A CN 200410088826 CN200410088826 CN 200410088826 CN 200410088826 A CN200410088826 A CN 200410088826A CN 1633995 A CN1633995 A CN 1633995A
- Authority
- CN
- China
- Prior art keywords
- delivery system
- sticky polymers
- skin
- drugs delivery
- contraceptive drugs
- 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.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 80
- 229940079593 drug Drugs 0.000 title claims abstract description 70
- 239000003433 contraceptive agent Substances 0.000 title claims abstract description 34
- 230000002254 contraceptive effect Effects 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 14
- 229920000642 polymer Polymers 0.000 claims abstract description 91
- 239000010410 layer Substances 0.000 claims abstract description 66
- 239000000203 mixture Substances 0.000 claims abstract description 51
- -1 aliphatic alcohol ester Chemical class 0.000 claims abstract description 20
- 239000003270 steroid hormone Substances 0.000 claims abstract description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims abstract description 17
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims abstract description 10
- MTHSVFCYNBDYFN-UHFFFAOYSA-N anhydrous diethylene glycol Natural products OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000011241 protective layer Substances 0.000 claims abstract description 3
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 claims description 39
- 239000003961 penetration enhancing agent Substances 0.000 claims description 27
- 229940088597 hormone Drugs 0.000 claims description 25
- 239000005556 hormone Substances 0.000 claims description 25
- 239000000080 wetting agent Substances 0.000 claims description 22
- 239000000186 progesterone Substances 0.000 claims description 20
- 229960003387 progesterone Drugs 0.000 claims description 20
- WWYNJERNGUHSAO-XUDSTZEESA-N (+)-Norgestrel Chemical group O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 WWYNJERNGUHSAO-XUDSTZEESA-N 0.000 claims description 18
- 229960004400 levonorgestrel Drugs 0.000 claims description 18
- 230000005540 biological transmission Effects 0.000 claims description 17
- 229940011871 estrogen Drugs 0.000 claims description 17
- 239000000262 estrogen Substances 0.000 claims description 17
- 239000000758 substrate Substances 0.000 claims description 16
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 14
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 14
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 14
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 claims description 13
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 claims description 13
- 229920001577 copolymer Polymers 0.000 claims description 13
- 229960002568 ethinylestradiol Drugs 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 11
- 230000002500 effect on skin Effects 0.000 claims description 10
- QQQMUBLXDAFBRH-UHFFFAOYSA-N dodecyl 2-hydroxypropanoate Chemical group CCCCCCCCCCCCOC(=O)C(C)O QQQMUBLXDAFBRH-UHFFFAOYSA-N 0.000 claims description 9
- 230000003203 everyday effect Effects 0.000 claims description 9
- 230000035558 fertility Effects 0.000 claims description 8
- 230000027758 ovulation cycle Effects 0.000 claims description 8
- 229920000058 polyacrylate Polymers 0.000 claims description 8
- 150000005215 alkyl ethers Chemical group 0.000 claims description 6
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 5
- 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 claims description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 5
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000005642 Oleic acid Substances 0.000 claims description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 5
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 5
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 claims description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 5
- 235000014655 lactic acid Nutrition 0.000 claims description 5
- 239000004310 lactic acid Substances 0.000 claims description 5
- 229920002367 Polyisobutene Polymers 0.000 claims description 4
- 239000004743 Polypropylene Substances 0.000 claims description 4
- 229960005309 estradiol Drugs 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 229920001155 polypropylene Polymers 0.000 claims description 4
- 229920001296 polysiloxane Polymers 0.000 claims description 4
- IMONTRJLAWHYGT-ZCPXKWAGSA-N Norethindrone Acetate Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@](C#C)(OC(=O)C)[C@@]1(C)CC2 IMONTRJLAWHYGT-ZCPXKWAGSA-N 0.000 claims description 3
- 239000005030 aluminium foil Substances 0.000 claims description 3
- 229960004976 desogestrel Drugs 0.000 claims description 3
- RPLCPCMSCLEKRS-BPIQYHPVSA-N desogestrel Chemical compound C1CC[C@@H]2[C@H]3C(=C)C[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 RPLCPCMSCLEKRS-BPIQYHPVSA-N 0.000 claims description 3
- 229930182833 estradiol Natural products 0.000 claims description 3
- 229920001684 low density polyethylene Polymers 0.000 claims description 3
- 239000004702 low-density polyethylene Substances 0.000 claims description 3
- 229960002985 medroxyprogesterone acetate Drugs 0.000 claims description 3
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 claims description 3
- 229940053934 norethindrone Drugs 0.000 claims description 3
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 claims description 3
- 229920006267 polyester film Polymers 0.000 claims description 3
- 229920006264 polyurethane film Polymers 0.000 claims description 3
- 229920000915 polyvinyl chloride Polymers 0.000 claims description 3
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 claims description 2
- 241001597008 Nomeidae Species 0.000 claims description 2
- 229920001903 high density polyethylene Polymers 0.000 claims description 2
- 239000004700 high-density polyethylene Substances 0.000 claims description 2
- 238000003860 storage Methods 0.000 abstract description 6
- 229960001760 dimethyl sulfoxide Drugs 0.000 abstract 1
- 239000003906 humectant Substances 0.000 abstract 1
- 239000010408 film Substances 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 230000008595 infiltration Effects 0.000 description 7
- 238000001764 infiltration Methods 0.000 description 7
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 6
- 239000000853 adhesive Substances 0.000 description 5
- 230000001070 adhesive effect Effects 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- ORKBYCQJWQBPFG-WOMZHKBXSA-N (8r,9s,10r,13s,14s,17r)-13-ethyl-17-ethynyl-17-hydroxy-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one;(8r,9s,13s,14s,17r)-17-ethynyl-13-methyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthrene-3,17-diol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1.O=C1CC[C@@H]2[C@H]3CC[C@](CC)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 ORKBYCQJWQBPFG-WOMZHKBXSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229940127234 oral contraceptive Drugs 0.000 description 3
- 239000003539 oral contraceptive agent Substances 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 239000004584 polyacrylic acid Substances 0.000 description 3
- 229920000193 polymethacrylate Polymers 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 239000005977 Ethylene Substances 0.000 description 2
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 238000007872 degassing Methods 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 238000003475 lamination Methods 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000000307 17β-estradiols Chemical class 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 239000004709 Chlorinated polyethylene Substances 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001328 Polyvinylidene chloride Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- ZJCCRDAZUWHFQH-UHFFFAOYSA-N Trimethylolpropane Chemical compound CCC(CO)(CO)CO ZJCCRDAZUWHFQH-UHFFFAOYSA-N 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 229920002433 Vinyl chloride-vinyl acetate copolymer Polymers 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 208000028922 artery disease Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- ZPOLOEWJWXZUSP-WAYWQWQTSA-N bis(prop-2-enyl) (z)-but-2-enedioate Chemical compound C=CCOC(=O)\C=C/C(=O)OCC=C ZPOLOEWJWXZUSP-WAYWQWQTSA-N 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 229920005549 butyl rubber Polymers 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 125000004386 diacrylate group Chemical group 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 229920005558 epichlorohydrin rubber Polymers 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000007970 homogeneous dispersion Substances 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 238000000643 oven drying Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229950000845 politef Drugs 0.000 description 1
- 229920001084 poly(chloroprene) Polymers 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 239000005033 polyvinylidene chloride Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- FBCQUCJYYPMKRO-UHFFFAOYSA-N prop-2-enyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC=C FBCQUCJYYPMKRO-UHFFFAOYSA-N 0.000 description 1
- QTECDUFMBMSHKR-UHFFFAOYSA-N prop-2-enyl prop-2-enoate Chemical compound C=CCOC(=O)C=C QTECDUFMBMSHKR-UHFFFAOYSA-N 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 230000037384 skin absorption Effects 0.000 description 1
- 231100000274 skin absorption Toxicity 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 208000012991 uterine carcinoma Diseases 0.000 description 1
- 206010046885 vaginal cancer Diseases 0.000 description 1
- 208000013139 vaginal neoplasm Diseases 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000004017 vitrification Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a percutaneous contraceptive drugs delivery system and method, wherein the delivery system (TCDS) comprises a back lining layer, a viscous polymeric medicine storage layer adhered on the back lining layer, a strippable protective layer adhered on the viscous polymeric medicine storage layer, the viscous polymeric medicine storage layer comprises skin permeable accelerant composition, humectant, viscous polymer, active dosage of one or more steroid hormones, wherein the skin permeable accelerant composition is a mixture of dimethyl sulphoxide, 2-hydroxypropanoic aliphatic alcohol ester, diethylene glycol alkyl ether and oleinic acid by the initial weight ratio of 2 : 1 : 1 : 0.8 to 5 : 1 : 1 : 0.8. The invention can substantially improve steroid hormone transdermal speed and increase TCDS effectiveness and convenience.
Description
Technical field
The present invention relates to a kind of percutaneous contraceptive drugs delivery system and method.
Background technology
The compositions of the estrogen of natural or synthetic and the progesterone of synthetic is often used to reach the purpose of contraception with the form of doses in the past; if use native female hormone (17-β estradiol) and progesterone (Progesterone) compositions with oral form; these two kinds of hormones can need to use very big dosage owing to carry out a large amount of first metabolism in liver, and this causes undesirable side effect through regular meeting.Although the compositions of main now artificial synthetic progesterone of use and estrogen overcomes these defectives as oral contraceptive.But use the oral contraceptive of this type still can produce certain side effect.
In the women who uses this type of oral contraceptive, thrombosis is higher with the sickness rate of the related artery disease that comprises apoplexy, myocardial infarction; Use the complication of this type of contraceptive also to comprise breast carcinoma, uterus carcinoma, cervical cancer and cancer of vagina.In addition, if mother continues to take, may cause fetal abnormality after pregnancy.
In the last few years, medical circle was paid special attention to the sustained-release administration system of developing implantable intrauterine, cervix uteri or intravaginal fertility restraining, with can be to human body long-term and controllably provide steroid hormone and reach the purpose of contraception.But these devices use and inconvenience.Up to now, this type of transmission system does not have yet and a kind ofly is considered to desirable and has no side effect.
Medicine is by skin absorbs, and promptly transdermal transmits and can reduce many undesirable side effect.The transdermal administration method can be avoided intravenous risk and inconvenience and absorption and the metabolic polytropy relevant with oral medication; Successive administration also can use the short medicine of biological half-life; Because reduced the degraded in digestive system, can reduce dosage every day, simple drug treatment is provided; In addition, if desired, can stop drug treatment apace by removing drug delivery system from skin surface.
Developed multiple contraceptive delivery system recent years and be used for female contraception by the skin effect.U.S. Pat 5,296,230 have described by reaching the sticky polymers doser of contraception purpose, this device comprises backing layer and polymer sheet layer, polymer sheet layer adheres on the backing layer and contains the estrogen and the progesterone hormone of doses, and the area of polymer sheet layer is about 20 square centimeters.
U.S. Pat 5,567,922 disclose estrogen 17 beta estradiols, ethinylestradiol or its compositions and natural progesterone, the transmission of progesterone in a doser, and this doser comprises the polyacrylate sticky polymers layer of backing layer and adjacent releasing hormone.
U.S. Pat 5,788, the transdermal delivery device of 983 reports is made up of backing layer and polymer drug storage layer.The drug storage layer have a plurality of in use with the zone of contact skin, and optionally contain the different Drug therapy reagent of the infiltration rate that provides variable.
U.S. Pat 5,762,956 have described the percutaneous contraceptive drugs transporter, and use this device to carry out method of contraception.This system comprises backing layer and sticky polymers substrate, has disperseed the composite hormone and the skin permeation enhancer compositions of control fertility effectively in the polymeric matrix.Sticky polymers substrate provides hormone and the dispersive place of skin penetration enhancer, and transmission system and the patient's who treats tight the contact with permission of skin is absorbed by skin.Usually the levonorgestrel of about 300-400pg/ml is released in the blood flow in the suitably long time.But found determining in the time that the levonorgestrel that discharges into this content of blood flow by skin is not enough to effectively and birth control safely.
World patent WO01/37770 has described the percutaneous contraceptive drugs transporter for 956 and has improved U.S. Pat 5,762, and purpose is further to improve the percutaneous rate of institute's transdermal thing.The percutaneous rate of levonorgestrel particularly.According to the description of patent WO01/37770, the content that is sent to levonorgestrel in the blood by this transdermal contraception device surpasses the required 200-600pg/ml content of contraception, surpasses the 400pg/ml content that the lucky described system in patent ' 956 reaches.In fact, when using 10 square centimeters paster, this system is sent to the content that levonorgestrel content in the blood can reach 2000 (Cmax Cmax) pg/ml, and simultaneously, this device also can the content of ethinylestradiol be controlled between about 35-75pg/ml in the blood with being sent to simultaneously.
But, particularly the percutaneous rate of levonorgestrel is still unsatisfactory to the rate of release of contraceptive for existing transdermal technology, be necessary to further develop new technique and device, improve institute's transdermal thing particularly levonorgestrel be sent to the percutaneous rate of blood so that safer, more effective realization contraception purpose.
Summary of the invention
The present invention is by a kind of novel transdermal administration technology, and a kind of safer, the transmission system and the method for practising contraception effectively are provided.
The present invention is achieved by the following technical solution:
A kind of percutaneous contraceptive drugs delivery system (TCDS) comprises backing layer (1), is attached to sticky polymers drug storing layer (2) on the backing layer (1), is attached to strippable backing layer (3) on sticky polymers drug storing layer (2) opposite side;
One or more steroid hormones that contain skin permeation enhancer compositions, wetting agent, sticky polymers, effective dose in the sticky polymers drug storing layer (2); Skin permeation enhancer compositions, wetting agent, one or more steroid hormones are dispersed or suspended in the sticky polymers;
Skin permeation enhancer compositions is 2: 1: 1 for the initial weight ratio: 0.8 to 5: 1: 1: 0.8 dimethyl sulfoxide, lactic acid aliphatic alcohol ester, diglycol monotertiary alkyl ether and oleic compositions;
The skin permeation enhancer compositions initial weight accounts for 10-50% in the initial gross weight of sticky polymers drug storing layer (2);
The wetting agent initial weight accounts for 0-10% in the initial gross weight of sticky polymers drug storing layer (2);
Preferred version of the present invention is that the lactic acid aliphatic alcohol ester in the skin permeation enhancer compositions is Lauryl lactate or the compositions that contains Lauryl lactate.
Another preferred version of the present invention is that the diglycol monotertiary alkyl ether in the skin permeation enhancer compositions is diethylene glycol monomethyl ether or diethylene glycol monoethyl ether.
Another preferred version of the present invention is that skin permeation enhancer compositions is a dimethyl sulfoxide, Lauryl lactate, and diethylene glycol monoethyl ether and oleic acid and initial weight ratio are 4: 1: 1: 0.8.
Another preferred version of the present invention is that skin penetration enhancer enhancer compositions initial weight accounts for 45% in the initial gross weight of sticky polymers drug storing layer (2).
Another preferred version of the present invention is that sticky polymers comprises polyacrylate sticky polymers, polyisobutylene sticky polymers or silicone sticky polymers, cellulosic polymer.Most preferably sticky polymers is the polyacrylate sticky polymers
Another preferred version of the present invention is that the thickness of sticky polymers drug storing layer (2) is between the 10-300 micron.
Another preferred version of the present invention is that wherein wetting agent is polyvinylpyrrolidone//vinyl acetate copolymers or polyvinylpyrrolidone.Most preferred wetting agent is a polyvinylpyrrolidone//vinyl acetate copolymers
The material of backing layer of the present invention (1) comprises the laminated product of high and low density polyethylene films, polypropylene screen, polyurethane film, polychloroethylene film or poly-phthalic acid ethyl polyester film and metal forming, and what contact with sticky polymers drug storing layer (2) is polymeric film in the laminate; The laminated product of preferably above-mentioned polymeric film and aluminium foil.
Backing layer (1) thickness is preferably between the 10-300 micron.
A preferred version more of the present invention is that steroid hormone is estrogen, progesterone hormone; Estrogen can be the estradiol or derivatives thereof; The progesterone hormone can be levonorgestrel, norethindrone, SH 420, Medroxyprogesterone Acetate, desogestrel or Alfasone material; Most preferably estrogen is that ethinylestradiol, progesterone hormone are levonorgestrels.
Preferred version of the present invention can transmit at least 10 μ g ethinylestradiols by skin in during 1 week more than 1 day at least every day; At least can every day in during about 1 week more than 1 day by skin transmission at least 30 μ g levonorgestrels.
The present invention is used for the size 7.5cm preferably of the paster of skin
2, 10cm
2Or 12.5cm
2
The invention provides a kind of percutaneous contraceptive drugs delivery system and percutaneous drug delivery is controlled the method for fertility, comprise the estrogen that minimum effective dose is provided in first three week and the progesterone hormone that make each menstrual cycle in continuous several menstrual cycle of this transmission system in can be during one section control fertility is desired; Preferably comprise each menstrual cycle of making in continuous several menstrual cycle of this transmission system in can be during one section control fertility is desired provide in first three week at least more than 1 day during about 1 week in, every day is by skin transmission at least 10 μ g ethinylestradiols; At least more than 1 day during about 1 week in every day by skin transmission at least 30 μ g levonorgestrels.
Percutaneous contraceptive drugs delivery system provided by the invention and method compare with other percutaneous contraceptive drugs delivery system, obviously improved the percutaneous rate of institute's with medicament, thereby reduced dermal osmosis time of institute's transdermal agent, make in the blood that hormone-content is high and play sufficient contraceptive efficacy, and make the side effect minimum.Owing to improved the transfer rate of transdermal, so this system can be made into the transdermal patches of reduced size, for user offers convenience.Be that the present invention has increased the effectiveness of TCDS and the convenience of user.
Below the present invention will be described in more detail:
One, backing layer (1)
The material that is preferably used as backing layer is the laminated product of metal forming and polymeric film, can select height and low density polyethylene films for use, polypropylene screen, polyurethane film, polychloroethylene film, the laminated product of poly-phthalic acid ethyl polyester film etc. and metal forming such as aluminium foil.In this type of laminated product, with the polymeric film in the normally laminate that sticky polymers substrate contacts.
The thickness of backing layer will be enough to provide protection and support function.Suitable thickness is between the 10-300 micron; Preferred thickness is between the 20-150 micron, and more preferably thickness is between the 30-100 micron.
Two, sticky polymers drug storing layer (2)
Comprise the dermal osmosis accelerator group compositions, wetting agent, the steroid hormone mixture that are dispersed in the sticky polymers substrate in the sticky polymers drug storing layer 2.
Sticky polymers drug storing layer 2 can use any acceptable method formation in the prior art, as spraying, solvent cast or lamination.
Be lower than expected value if find the adhesive force of sticky polymers drug storing layer 2, can reduce the concentration of the skin permeation enhancer compositions in sticky polymers drug storing layer 2 subregions, as the surface portion of independent use sticky polymers substrate, or make sticky polymers drug storing layer 2 surface portions have lower dermal osmosis accelerator concentration as drug storing layer.
Sticky polymers drug storing layer 2 thickness are between the 10-300 micron, and preferred thickness is between the 20-180 micron, and most preferred thickness is between the 30-150 micron.
(1) skin penetration enhancer
Because skin outermost layer horny layer is to the resistance maximum of molecule infiltration, so for improving the infiltration rate of drug molecule, transdermal drug transmits system must improve cuticular permeability especially.
Employed dermal osmosis accelerator comprises dimethyl sulfoxide among the present invention, lactic acid aliphatic alcohol ester, diglycol monotertiary alkyl ether and oleic compositions.Preferred dimethyl sulfoxide, Lauryl lactate, diglycol monotertiary alkyl ether and oleic compositions.Oleic acid is a kind of straight chain unsaturated fatty acid, and chemical formula is C
18H
34O
2, molecular weight is 282.The inventor find when the skin permeation enhancer compositions of the uniqueness that will especially comprise oleic acid be 2: 1: 1 with initial weight ratio respectively: 0.8 to 5: 1: 1: 0.8, preferred 4: 1: 1: when 0.8 special ratios is evenly dispersed on the sticky polymers substrate, employed sticky polymers and wetting agent can make dispersive estrogen and progesterone solubilising jointly among said composition and the present invention, thereby greatly improved the meltage of hormone in TCDS, obtain better percutaneous permeability, simultaneously, the cohesiveness of TCDS and adhesive force are also satisfactory.
The skin permeation enhancer compositions initial weight preferably accounts for the 10-50% of sticky polymers drug storing layer 2 initial gross weights; Preferred 40-50%; The best is 45%.
(2) steroid hormone
The medicament that is dispersed in the sticky polymers substrate can be can practise contraception also to pass through one or more hormones arbitrarily of dermal administration.Estrogen that preferred employed hormone is a steroid hormone and progesterone hormone; Estrogen can be estradiol and derivant thereof; The progesterone hormone can be levonorgestrel, norethindrone, SH 420, Medroxyprogesterone Acetate, desogestrel or Alfasone material.
The present invention most preferably estrogen is that ethinylestradiol, progesterone hormone are levonorgestrels.
Usually contain in the sticky polymers substrate process of hormone in manufacturing, progesterone chemical compound and estrogen steroidal can disperse or dissolve simultaneously, also can disperse or dissolve respectively.
(3) wetting agent
Wetting agent is dispersed among the sticky polymers substrate, the water content of the humidity of may command polymeric matrix, adjusting preparation; In sticky polymers substrate, add wetting agent and make TCDS can absorb the moisture of skin surface, help reducing scytitis, and TCDS comes off when preventing that long-term (as 7 days) use TCDS.
Wetting agent can be the conventional wetting agent that uses in the medical industry, as polyvinyl pyrrolidone.Can select for use molecular weight to be about 50, polyvinyl pyrrolidone/vinyl acetate of 000, preferred wetting agent is by being positioned at U.S. Wayne, the ISP Intermational Special Products of New Jersey, Inc. the PVP/VA S-630 that is provided, wherein the content of polyvinylpyrrolidone (PVP) is about 60% of mixture total weight amount, and the content of vinyl acetate (VA) is about 40% of mixture total weight amount.
The consumption of employed wetting agent preferably accounts for the 0-10% of sticky polymers drug storing layer 2 gross weights; The preferred 1-3% of institute; The best is 1.0%.
(4) sticky polymers
Sticky polymers is made by the acceptable macromolecular material of biology, because the dissolving of substrate or erosion can influence the rate of release and the adhesive ability of hormone, so will avoid using soluble polymer.Suitable polymers has biological and the medical compatibility, and no anaphylactogen is with the tissue compatible that contacts but can not dissolve.
Usually, those polymer that are used to form the sticky polymers layer of biocompatibility be can allow hormone with the speed of control by wherein thin film or the polymer of coating.For example polyacrylic acid sticky polymers, silicone sticky polymers or polyisobutylene polymer.
The examples of materials of sticky polymers substrate comprises polyethylene, polypropylene, ethylene/propene copolymer, ethene/acrylic ester copolymer, ethylene, the polydimethylsiloxane of silicone elastomer, especially pharmaceutical grade, neoprene, polyisobutylene, polyacrylate, chlorinated polyethylene, polrvinyl chloride, vinyl chloride vinyl acetate copolymer, crosslinked polymethacrylates (hydrogel), polyvinylidene chloride, polyethylene terephthalate, butyl rubber, epichlorohydrin rubber, ethylene/vinyl alcohol copolymer, ethylene-alkene ethoxy-ethanol copolymer; Silicone copolymer, as polysiloxanes-polymethacrylate copolymer, polysiloxanes-alkylene copolymer (as, polysiloxanes-vinyl silanes copolymer) etc.; Fiber table polymer, as methyl or ethyl cellulose, the mutual ester of hydroxypropyl cellulose and fiber, Merlon; Politef etc.
The sticky polymers substrate of preferred biocompatibility is selected from the subambient polymer of vitrification point.Polymer can have certain degree of crystallinity in room temperature, but and unnecessary.Can in these polymer, add crosslinkable monomeric unit or position.As in polyacrylate, adding crosslinkable monomer, it provides crosslinked position to polyacrylate polymers, the polymethacrylates that comprises polyhydric alcohol is as diacrylate Aden ester and dimethacrylate Aden ester, the trimethyl acrylic ester of trimethylolpropane etc.Other can provide the monomer of such position to comprise allyl acrylate, allyl methacrylate, diallyl maleate etc.
The preferred sticky polymers of the present invention is commodity Duro-Tak87-4098 polyacrylic acid sticky polymers by name, and by being positioned at U.S. Bridgewater, the national starch chemical company of New Jersey provides.
Description of drawings
Fig. 1 is the schematic cross-section of TCDS paster, wherein: 1, backing layer 2, sticky polymers drug storing layer 3, protective layer
Fig. 2 uses the ethinylestradiol of Comparative Examples TCDS patch formulation transmission and the vitro skin osmotic figure of levonorgestrel for when testing on people's isolated skin.
Fig. 3 uses the ethinylestradiol of embodiment of the invention TCDS patch formulation transmission and the vitro skin osmotic figure of levonorgestrel for when testing on people's isolated skin.
The specific embodiment
The making of TCDS paster
When the TCDS paster is made, earlier wetting agent is mixed with skin permeation enhancer compositions solution, add also stirring of hormone again, make the steroid hormone medicine dissolution or be scattered in the solution that contains wetting agent and skin permeation enhancer compositions.
The consumption of skin permeation enhancer compositions depends on the transfer rate of steroid hormone.Preferred skin permeation enhancer compositions accounts for the 30-50% of sticky polymers drug storing layer initial weight; More preferably skin permeation enhancer compositions accounts for the 40-50% of sticky polymers drug storing layer initial weight.
Determine the consumption of the steroid hormone that adds desired treatment time according to the dosage of steroid hormone and each administration unit.Preferably in sticky polymers substrate the content of dispersive steroid hormone greater than the dosage of desired transmission.Preferably doubly than the excessive about 5-50 of Transdermal absorption required dosage; More preferably excessive about 10-25 doubly.
Sticky polymers preferably uses the polyacrylic acid sticky polymers.The viscous polymer solution adding has been disperseed in dermal osmosis accelerator/wetting agent (PVP/VA) solution of hormonal medicaments.
Use the mixture of agitator abundant polypropylene acid esters adhesive copolymer and PVP/VA/ promoter steroid hormone solution, form homogeneous dispersion or the solution of steroid hormone in the polyacrylate adhesive copolymer.Compositions leaves standstill to 3 hours-12 hours, until the degassing fully.
After the degassing finishes, sticky polymers is coated on the backing layer material, as 3M Co., the Scotch Pak 1109 that St.Paul Minn. produces is subsequently 60 ℃ of dryings 15 minutes.Dried sticky polymers and a slice, the release liner of same size (as 3M Co., the Scotch Pak 1012 that St.Paul Minn. produces)-neat lamination is split into the thin slice of percutaneous contraceptive drugs delivery system.Use steel ruler mould and hydraulic press cutting gained sticky polymers substrate thin slice to form disk with required form and size.Usually the disk area is no more than 100 square centimeters.Preferred disk is about the 5-100 square centimeter, is more preferably about 80 square centimeters of 8-.More preferably the disk size is about about 60 square centimeters of 10-.Preferred 10 square centimeters disk because although size is less, but still can disperse high-load hormone.The shape of disk can be different, and they can be square, circle, rectangle or other desirable shape.The appropriate packaging that is used for storing can be put in the unit administration unit of gained percutaneous contraceptive drugs delivery system, as paper bag and/or metallic foil bag, when being saved in skin-penetrating therapeutic.
Further describe the present invention with reference to following detailed embodiment.But following examples are used to further specify the present invention, rather than limit its scope.
Embodiment:
As following table 1 is each contained composition weight of starting soln:
| Component | Embodiment | Comparative Examples |
| Ethinylestradiol | 0.65g | 0.65g |
| Levonorgestrel | 1.16g | 1.16g |
| PVP/VA copolymer (S-630) | 0.50g | 0.50g |
| Enhancer compositions | Dimethyl sulfoxide: 26.50g lactic acid lauryl ester: 6.60g diethylene glycol monoethyl ether: 6.60g oleic acid: 5.30g | Dimethyl sulfoxide: 26.50g lactic acid lauryl ester: 6.60g ethyl lactate: 6.60g capric acid: 5.30g |
| Sticky polymers (Dura-Tak 87-4098) | 52.69g | 52.69g |
Other embodiment adjusts the consumption of above-mentioned each component in scope of the present invention, products obtained therefrom is still effective.
Manufacturing process:
TCDS paster with above prescription is made according to the following steps: take by weighing steroid hormone, wetting agent successively, put into vial.The skin permeation enhancer compositions that adding table 1 is given also shakes vial until hormone and the dissolving of PVP/VA copolymer.After adding poly-propionic ester viscous polymer solution vial is sealed.With magnetic stirring bar room temperature with about 200rpm blender jar in material formed uniform solution in 6 hours.The vial standing over night is until all bubble collapses.
With the gained solution coat at a slice backing layer＜Scotch Pak 1109,3M Co., St Paul, Minn. on, gained thickness is 600 microns, subsequently 65 ℃ of oven dryings 15 minutes.After the drying, about 100 microns of the thickness of sticky polymers drug storage layer.
Vitro permeation studies
For confirming that TCDS patch formulation described above can realize the ethinylestradiol that needs and the dermal osmosis speed of levonorgestrel, end user's isolated skin carries out the external drug osmotic research of gained paster in the system of the dermal osmosis chamber of the parallel type of vaila-Chien.With the resulting sample concentration in efficient liquid phase chromatographic analysis continuous filter.Concrete grammar is that people's isolated skin sample is placed in the valia-Chien continuous filter (Chinese Academy of Sciences's chemistry institute glass room system), make skin horny layer by the continuous filter side outwardly, on skin, fix the preparation capable of permeating skin that comprises medicine then.In the continuous filter, add the normal saline solution that 3.4ml comprises 40% PEG400, and stir and control the circulator bath temperature at 37 ° of C at whole experimental session.After this, take out the normal saline solution sample that 100 μ l comprise 40% PEG400 termly, carry out efficient liquid phase chromatographic analysis, with transdermal accumulation medication amount (the μ g/cm of analytical unit area
2).Analyze drug accumulation amount (μ g/cm
2Hr) over time.The sample of preparing by embodiment and Comparative Examples prescription uses different skin to test respectively 3 times, and results averaged is calculated medicine thus and seen through the average infiltration rate of skin.
The vitro skin infiltration result that research obtains ethinylestradiol and levonorgestrel as table 2,3 and Fig. 2,3 shown in.
Table 2: ethinylestradiol and levonorgestrel see through the cumulant of human body skin
| Time (hour) | Embodiment | Comparative Examples | Embodiment | Comparative Examples |
| Ethinylestradiol (mcg/cm2) | Ethinylestradiol (mcg/cm2) | Levonorgestrel (mcg/cm2) | Levonorgestrel (mcg/cm2) | |
| ?4 | ??-- | ?-- | ?-- | ?-- |
| ?8 | ??-- | ?-- | ?3.72±0.28 | ?0.75±0.21 |
| ?24 | ?10.67±5.67 | ?5.73±2.06 | ?8.75±0.80 | ?1.37±0.49 |
| ?32 | ?15.20±5.51 | ?7.90±3.79 | ?10.60±1.11 | ?1.57±0.56 |
| ?48 | ?27.00±6.94 | ?12.79±5.53 | ?16.69±2.76 | ?2.16±0.67 |
| ?56 | ?32.77±7.75 | ?13.99±5.44 | ?18.51±3.27 | ?2.34±0.71 |
| ????72 | ????39.44±7.59 | ????19.64±6.35 | ????21.11±2.93 | ????2.99±0.66 |
| ????80 | ????41.04±8.88 | ????21.86±7.79 | ????21.69±2.97 | ????3.14±0.60 |
| ????96 | ????51.22± ????????11.53 | ????27.72±9.32 | ????24.36±2.69 | ????3.61±0.68 |
Table 3: the infiltration rate that ethinylestradiol and levonorgestrel see through human body skin over time
| Time (hour) | Embodiment | Comparative Examples | Embodiment | Comparative Examples |
| Ethinylestradiol (mcg/cm2.h) | Ethinylestradiol (mcg/cm2.h) | Levonorgestrel (mcg/cm2.h) | Levonorgestrel (mcg/cm2.h) | |
| ?4 | ?-- | ??-- | ??-- | ??-- |
| ?8 | ?-- | ??-- | ??-- | ??-- |
| ?24 | ?0.45±0.23 | ?0.24±0.09 | ?0.38±0.05 | ?0.25±0.03 |
| ?32 | ?0.48±0.17 | ?0.27±0.08 | ?0.33±1.03 | ?0.22±0.20 |
| ?48 | ?0.56±0.15 | ?0.27±0.12 | ?0.35±0.06 | ?0.20±0.06 |
| ?56 | ?0.58±0.14 | ?0.25±0.10 | ?0.33±0.06 | ?0.18±0.06 |
| ?72 | ?0.56±0.09 | ?0.27±0.09 | ?0.30±0.04 | ?0.18±0.04 |
| ?80 | ?0.51±0.11 | ?0.27±0.10 | ?0.27±0.04 | ?0.17±0.03 |
| ?96 | ?0.54±0.12 | ?0.29±0.10 | ?0.25±0.03 | ?0.16±0.03 |
The result of contrast table 2, table 3 and Fig. 2, Fig. 3, skin absorption promoter compositions of the present invention has higher infiltration rate as the absorption enhancer of ethinylestradiol and levonorgestrel.
Claims (18)
1, a kind of percutaneous contraceptive drugs delivery system comprises backing layer (1), is attached to sticky polymers drug storing layer (2) on the backing layer (1), is attached to strippable protective layer (3) on sticky polymers drug storing layer (2) opposite side;
Contain skin permeation enhancer compositions, wetting agent, sticky polymers in the sticky polymers drug storing layer (2), can see through skin and reach one or more steroid hormones of contraception purpose, effective dose; Skin permeation enhancer compositions, wetting agent, steroid hormone are dispersed in the sticky polymers substrate;
Skin permeation enhancer compositions is 2: 1: 1 for the initial weight ratio: 0.8 to 5: 1: 1: 0.8 dimethyl sulfoxide, lactic acid aliphatic alcohol ester, diglycol monotertiary alkyl ether and oleic mixture;
The skin permeation enhancer compositions initial weight accounts for 10-50% in the initial gross weight of sticky polymers drug storing layer (2);
The wetting agent initial weight accounts for 0-10% in the initial gross weight of sticky polymers drug storing layer (2).
2, a kind of percutaneous contraceptive drugs delivery system according to claim 1, wherein, the lactic acid aliphatic alcohol ester in the dermal osmosis accelerator is Lauryl lactate or the mixture that contains Lauryl lactate.
3, a kind of percutaneous contraceptive drugs delivery system according to claim 1, the diglycol monotertiary alkyl ether in the skin permeation enhancer compositions wherein is diethylene glycol monomethyl ether or diethylene glycol monoethyl ether.
4, a kind of percutaneous contraceptive drugs delivery system according to claim 1, skin permeation enhancer compositions wherein is a dimethyl sulfoxide, Lauryl lactate, diethylene glycol monoethyl ether and oleic acid and initial weight ratio are 4: 1: 1: 0.8.
5, a kind of percutaneous contraceptive drugs delivery system according to claim 4, skin permeation enhancer compositions initial weight wherein accounts for 45% in the initial gross weight of sticky polymers drug storing layer (2).
6, according to claim 1,2,3,4 or 5 described a kind of percutaneous contraceptive drugs delivery systems, sticky polymers wherein comprises polyacrylate sticky polymers, polyisobutylene sticky polymers or silicone sticky polymers, cellulosic polymer.
7, a kind of percutaneous contraceptive drugs delivery system according to claim 6, wherein the thickness of sticky polymers drug storing layer (2) is between the 10-300 micron.
8, according to claim 1,2,3,4 or 5 described a kind of percutaneous contraceptive drugs delivery systems, wetting agent wherein is polyvinylpyrrolidone//vinyl acetate copolymers or polyvinylpyrrolidone.
9, according to claim 1,2,3,4 or 5 described a kind of percutaneous contraceptive drugs delivery systems, the material of backing layer wherein (1) comprises the laminated product of high and low density polyethylene films, polypropylene screen, polyurethane film, polychloroethylene film or poly-phthalic acid ethyl polyester film and metal forming, and what contact with sticky polymers drug storing layer (2) is polymeric film in the laminate.
10, a kind of percutaneous contraceptive drugs delivery system according to claim 9, the material of backing layer wherein (1) is the laminated product of above-mentioned polymeric film and aluminium foil.
11, a kind of percutaneous contraceptive drugs delivery system according to claim 10, backing layer wherein (1) thickness is between the 10-300 micron.
12, according to claim 1,2,3,4 or 5 described a kind of percutaneous contraceptive drugs delivery systems, steroid hormone wherein is estrogen and progesterone hormone.
13, a kind of percutaneous contraceptive drugs delivery system according to claim 12, estrogen wherein is estradiol and derivant thereof; The progesterone hormone is levonorgestrel, norethindrone, SH 420, Medroxyprogesterone Acetate, desogestrel, Alfasone material.
14, a kind of percutaneous contraceptive drugs delivery system according to claim 13, estrogen wherein are that ethinylestradiol, progesterone hormone are levonorgestrels.
15, a kind of percutaneous contraceptive drugs delivery system according to claim 14 wherein can transmit at least 10 μ g ethinylestradiols by skin in during 1 week more than 1 day at least every day; At least can every day in during about 1 week more than 1 day by skin transmission at least 30 μ g levonorgestrels.
16, a kind of percutaneous contraceptive drugs delivery system according to claim 15, the size that wherein is used for the paster of skin is 7.5cm
2, 10cm
2Or 12.5cm
2
17, the described a kind of percutaneous contraceptive drugs delivery system of above-mentioned arbitrary claim uses skin and the method for control fertility, comprises the estrogen that minimum effective dose is provided in first three week and the progesterone hormone that make each menstrual cycle in continuous several menstrual cycle of this transmission system in can be during one section control fertility is desired.
18, a kind of percutaneous contraceptive drugs delivery system according to claim 17 uses and method of contraception skin, comprise each menstrual cycle of making in continuous several menstrual cycle of this transmission system in can be during one section control fertility is desired provide in first three week at least more than 1 day during about 1 week in, every day is by skin transmission at least 10 μ g ethinylestradiols; At least more than 1 day during about 1 week in every day by skin transmission at least 30 μ g levonorgestrels.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100888264A CN1313084C (en) | 2004-11-05 | 2004-11-05 | Percutaneous contraceptive drugs delivery system and method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100888264A CN1313084C (en) | 2004-11-05 | 2004-11-05 | Percutaneous contraceptive drugs delivery system and method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1633995A true CN1633995A (en) | 2005-07-06 |
| CN1313084C CN1313084C (en) | 2007-05-02 |
Family
ID=34847524
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100888264A Active CN1313084C (en) | 2004-11-05 | 2004-11-05 | Percutaneous contraceptive drugs delivery system and method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1313084C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526069A (en) * | 2011-12-31 | 2012-07-04 | 刘布鸣 | External norgesterone acetate contraception preparation and preparation method thereof |
| WO2015128280A1 (en) * | 2014-02-25 | 2015-09-03 | Lvs-Capital Gmbh | Topical cosmetic or pharmaceutical composition |
| CN105997951A (en) * | 2016-06-12 | 2016-10-12 | 润和生物医药科技(汕头)有限公司 | Cutaneous penetration system containing rivastigmine and preparation method |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5296230A (en) * | 1985-02-25 | 1994-03-22 | Rutgers, The State University Of New Jersey | Transdermal fertility control system and process |
| KR100215027B1 (en) * | 1997-01-27 | 1999-08-16 | 성재갑 | Composition for transdermal administration of steroid drugs and formulation containing same |
| ES2338860T3 (en) * | 1999-11-24 | 2010-05-13 | Agile Therapeutics, Inc. | SYSTEM AND PROCEDURE FOR ADMINISTRATION OF IMPROVED TRANSDERMIC CONTRACEPTIVE. |
-
2004
- 2004-11-05 CN CNB2004100888264A patent/CN1313084C/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102526069A (en) * | 2011-12-31 | 2012-07-04 | 刘布鸣 | External norgesterone acetate contraception preparation and preparation method thereof |
| CN102526069B (en) * | 2011-12-31 | 2015-09-23 | 刘布鸣 | External norgesterone acetate contraception and preparation method thereof |
| WO2015128280A1 (en) * | 2014-02-25 | 2015-09-03 | Lvs-Capital Gmbh | Topical cosmetic or pharmaceutical composition |
| CN105997951A (en) * | 2016-06-12 | 2016-10-12 | 润和生物医药科技(汕头)有限公司 | Cutaneous penetration system containing rivastigmine and preparation method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1313084C (en) | 2007-05-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR950008164B1 (en) | Transdermal fertility control system and process | |
| CN1188189C (en) | Transdermal patch and method for administering 17-deacetyl norgestimate alone or in combination with estrogen | |
| US5762956A (en) | Transdermal contraceptive delivery system and process | |
| EP0275716B1 (en) | Transdermal estrogen/progestin dosage unit, and fertility control kit comprising said dosage unit. | |
| CN101897683B (en) | Transdermal hormone delivery system: compositions and methods | |
| KR960000553B1 (en) | Transdermal absorption dosage unit for estradiol and other estrogenic steroids and process for adminstration | |
| JP4841781B2 (en) | Improved transdermal contraceptive delivery system and method | |
| TWI511733B (en) | Transdermal estrogen device and use | |
| JPH04504109A (en) | Estrogen/progestin transdermal administration unit, its system and process | |
| CN101940790A (en) | Novel penetration-promoting agent composition and application thereof to transdermal administration system | |
| CZ187796A3 (en) | Pharmaceutical preparation | |
| CN1313084C (en) | Percutaneous contraceptive drugs delivery system and method | |
| CN1400897A (en) | Transdermal delivery LASOFOXIFENE | |
| RU2204417C2 (en) | Device for carrying out transcutaneous trimegestron administration | |
| CN108606963B (en) | Compound contraceptive patch containing drospirenone and estrogen, preparation method and application | |
| KR100498199B1 (en) | Novel Devices for Transdermal Administering of Trimegestone | |
| WO2003101461A1 (en) | Norethindrone sustained release formulations and methods associated therewith | |
| CN1742708A (en) | Transdermal administration pressure-sensitive gel composite substrate | |
| NO880356L (en) | DOSAGE UNIT FOR ABSORPTION OF OESTRADIOL AND OTHER OESTROGEN STEREOIDS THROUGH THE SKIN, AND PROCEDURE FOR ADMINISTRATING THE STEREOIDS. | |
| CN1762366A (en) | Levonogestrel transdermal control-releasing transfer system and its multifunctional patch | |
| WO2014159778A1 (en) | Transdermal drug delivery system containing fentanyl |
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 | ||
| ASS | Succession or assignment of patent right |
Free format text: FORMER OWNER: YANG MINGJING Effective date: 20150813 Owner name: RUNHE BIOLOGICAL MEDICINE SCIENCE-TECHNOLOGY CO., Free format text: FORMER OWNER: ZHENG HUIYI Effective date: 20150813 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20150813 Address after: 515000 Lu Rongsheng Science Park, University of Guangdong, Shantou Patentee after: RUNBIO BIOTECH Co.,Ltd. Address before: 515041 Guangdong city of Shenzhen Province Overseas Chinese Town Lake Garden Yan Tsui court 26A Patentee before: Zheng Huiyi Patentee before: Yang Mingjing |
|
| CP01 | Change in the name or title of a patent holder |
Address after: Room 116, Floor 1, Transportation Bureau Building, No. 95, Yingbin Avenue, Huacheng Street, Huadu District, Guangzhou, Guangdong, 510000 Patentee after: Guangdong Iconas Biomedical Technology Co.,Ltd. Address before: Room 116, Floor 1, Transportation Bureau Building, No. 95, Yingbin Avenue, Huacheng Street, Huadu District, Guangzhou, Guangdong, 510000 Patentee before: Guangdong Iconas Biomedical Technology Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP03 | Change of name, title or address | ||
| CP03 | Change of name, title or address |
Address after: Room 116, Floor 1, Transportation Bureau Building, No. 95, Yingbin Avenue, Huacheng Street, Huadu District, Guangzhou, Guangdong, 510000 Patentee after: Guangdong Iconas Biomedical Technology Co.,Ltd. Address before: 515000 in Rongsheng science and Technology Park, University Road, Shantou City, Guangdong Province Patentee before: RUNBIO BIOTECH Co.,Ltd. |