JPH0477419A - Formulation for patching - Google Patents
Formulation for patchingInfo
- Publication number
- JPH0477419A JPH0477419A JP18709390A JP18709390A JPH0477419A JP H0477419 A JPH0477419 A JP H0477419A JP 18709390 A JP18709390 A JP 18709390A JP 18709390 A JP18709390 A JP 18709390A JP H0477419 A JPH0477419 A JP H0477419A
- Authority
- JP
- Japan
- Prior art keywords
- layer
- drug
- preparation
- adhesive
- patch
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000009472 formulation Methods 0.000 title abstract description 23
- 239000000203 mixture Substances 0.000 title abstract description 23
- 239000010410 layer Substances 0.000 claims abstract description 94
- 239000003814 drug Substances 0.000 claims abstract description 60
- 229940079593 drug Drugs 0.000 claims abstract description 58
- 239000010408 film Substances 0.000 claims abstract description 32
- 239000010409 thin film Substances 0.000 claims abstract description 30
- 239000012790 adhesive layer Substances 0.000 claims abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229920006267 polyester film Polymers 0.000 claims abstract description 20
- 230000005068 transpiration Effects 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims description 60
- 239000000853 adhesive Substances 0.000 claims description 22
- 230000001070 adhesive effect Effects 0.000 claims description 22
- 239000002245 particle Substances 0.000 claims description 9
- 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 7
- 239000010419 fine particle Substances 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 5
- 239000003522 acrylic cement Substances 0.000 claims description 4
- 229960003387 progesterone Drugs 0.000 claims description 3
- 239000000186 progesterone Substances 0.000 claims description 3
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims 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 claims 1
- 239000004925 Acrylic resin Substances 0.000 claims 1
- 229920000178 Acrylic resin Polymers 0.000 claims 1
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 claims 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 claims 1
- 239000000006 Nitroglycerin Substances 0.000 claims 1
- DDNCQMVWWZOMLN-IRLDBZIGSA-N Vinpocetine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C=C(C(=O)OCC)N5C2=C1 DDNCQMVWWZOMLN-IRLDBZIGSA-N 0.000 claims 1
- YWXYYJSYQOXTPL-JGWLITMVSA-N [(3r,3ar,6s,6as)-3-hydroxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-6-yl] nitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-JGWLITMVSA-N 0.000 claims 1
- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims 1
- 229960001736 buprenorphine Drugs 0.000 claims 1
- 229960005309 estradiol Drugs 0.000 claims 1
- 229930182833 estradiol Natural products 0.000 claims 1
- 229960003711 glyceryl trinitrate Drugs 0.000 claims 1
- 229960004958 ketotifen Drugs 0.000 claims 1
- 229960002715 nicotine Drugs 0.000 claims 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims 1
- 229960000744 vinpocetine Drugs 0.000 claims 1
- 239000004744 fabric Substances 0.000 abstract description 16
- 239000012510 hollow fiber Substances 0.000 abstract description 14
- 238000010521 absorption reaction Methods 0.000 abstract description 9
- WSSSPWUEQFSQQG-UHFFFAOYSA-N 4-methyl-1-pentene Chemical compound CC(C)CC=C WSSSPWUEQFSQQG-UHFFFAOYSA-N 0.000 abstract description 2
- 238000010030 laminating Methods 0.000 abstract 1
- 230000002093 peripheral effect Effects 0.000 abstract 1
- 210000003491 skin Anatomy 0.000 description 20
- 239000000463 material Substances 0.000 description 17
- 206010040880 Skin irritation Diseases 0.000 description 16
- 231100000475 skin irritation Toxicity 0.000 description 16
- 230000036556 skin irritation Effects 0.000 description 16
- -1 polyethylene Polymers 0.000 description 11
- 239000000835 fiber Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 230000007794 irritation Effects 0.000 description 7
- 230000035699 permeability Effects 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- 150000002739 metals Chemical class 0.000 description 6
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 229920000728 polyester Polymers 0.000 description 5
- 229920000139 polyethylene terephthalate Polymers 0.000 description 5
- 239000005020 polyethylene terephthalate Substances 0.000 description 5
- 238000007789 sealing Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000004745 nonwoven fabric Substances 0.000 description 4
- 230000000149 penetrating effect Effects 0.000 description 4
- 239000013557 residual solvent Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000002759 woven fabric Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 208000010201 Exanthema Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229910052788 barium Inorganic materials 0.000 description 3
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 201000005884 exanthem Diseases 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 206010037844 rash Diseases 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 229920002292 Nylon 6 Polymers 0.000 description 2
- 229920002302 Nylon 6,6 Polymers 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000037374 absorbed through the skin Effects 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000001788 irregular Effects 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229940124636 opioid drug Drugs 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920003207 poly(ethylene-2,6-naphthalate) Polymers 0.000 description 2
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 239000011112 polyethylene naphthalate Substances 0.000 description 2
- 229920000098 polyolefin Polymers 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 210000000434 stratum corneum Anatomy 0.000 description 2
- 229920002994 synthetic fiber Polymers 0.000 description 2
- 239000012209 synthetic fiber Substances 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920006243 acrylic copolymer Polymers 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- UBAZGMLMVVQSCD-UHFFFAOYSA-N carbon dioxide;molecular oxygen Chemical compound O=O.O=C=O UBAZGMLMVVQSCD-UHFFFAOYSA-N 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
- 239000012141 concentrate Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical class O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 230000006355 external stress Effects 0.000 description 1
- 210000004709 eyebrow Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 229920002223 polystyrene 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
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000583 progesterone congener Substances 0.000 description 1
- 239000002964 rayon Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 231100001068 severe skin irritation Toxicity 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】
〈産業上の利用分野〉
本発明は各種疾患の治療に用いることのできる貼付用の
製剤に関する。DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a patch preparation that can be used for the treatment of various diseases.
〈従来の技術及び発明が解決しようとする課題〉医薬品
の投与経路として従来から経口、注射。<Prior art and problems to be solved by the invention> Oral administration and injection have traditionally been the administration routes for pharmaceuticals.
直腸投与の他、局所投与として軟膏等が多用されてきた
。さらに近年、全身に作用する薬物を経皮的に投与する
技術の開発が進み、数種の薬物については実際に臨床的
に利用されるようになった。In addition to rectal administration, ointments and the like have been frequently used for local administration. Furthermore, in recent years, the development of techniques for transdermally administering drugs that act on the whole body has progressed, and several types of drugs have actually come to be used clinically.
薬物を経皮投与することによって、例えば経口投与され
た場合に薬物がうける肝臓での初回通過効果を避けるこ
とができ、従って経口投与や注射投与に比較してはるか
に安定した薬物血中濃度を維持できること、またその持
続時間も長いこと、薬物による重大な副作用が発生した
ときに経皮投与製剤は除剤が容易であること等、多くの
利点が得られることが判っている。Transdermal administration of drugs avoids, for example, the first-pass effect that drugs undergo in the liver when administered orally, thus resulting in much more stable blood drug concentrations compared to oral or injection administration. It has been found that transdermal preparations have many advantages, such as being able to be maintained and lasting for a long time, and being easy to remove when serious drug-induced side effects occur.
かかる利点に注目し、多くの医薬品について、従来製剤
から経皮投与製剤への変更が検討されている。Taking note of these advantages, many pharmaceuticals are being considered to change from conventional formulations to transdermal formulations.
しかしながら、経皮投与製剤の医薬品の臨床での応用が
進むにつれて、経皮投与経路の困難性。However, as the clinical application of transdermal pharmaceutical preparations progresses, the difficulties of the transdermal administration route.
問題点も明らかになってきた。Problems have also become clear.
それらのいくつかは以下の通りである。Some of them are as follows.
（１）経皮投与製剤についての最大の問題点は局所刺激
性、皮膚カブレの発生である。ある統計によると密封型
の経皮投与製剤による皮膚カブレの発生率は２０〜５０
％にもなっている。(1) The biggest problem with transdermal preparations is local irritation and skin irritation. According to some statistics, the incidence of skin irritation due to sealed transdermal preparations is 20 to 50%.
%.
しかしながら患者は経皮投与製剤の持つ長所のため、た
とえ皮膚カブレが発生しても、かかる製剤を利用せざる
を得ないケースも多い。However, because of the advantages of transdermal preparations, patients are often forced to use such preparations even if skin irritation occurs.
（２）一般に、現在臨床に使用されている医薬品の薬物
は経皮吸収されにくいものが多く、経皮吸収されるもの
でも臨床有効量を吸収させるなめには貼付面積を大きく
しなり、吸収促進のための助剤を使用する等の必要があ
る。(2) In general, many of the drugs currently in clinical use are difficult to absorb through the skin, and even for drugs that can be absorbed through the skin, in order to absorb a clinically effective amount, the area of the patch must be large to promote absorption. It is necessary to use auxiliary agents for this purpose.
しかしながら、貼付面積を大きくしたり、吸収促進剤を
用いたりすることは皮膚カブレ面積の増大、皮膚カブレ
程度の悪化をもたらすことが多い。However, increasing the application area or using an absorption enhancer often results in an increase in the area of skin irritation and worsening of the degree of skin irritation.
そこで、皮膚カブレの発生を抑制しつつ臨床有効量の薬
物を吸収させることのできる経皮投与製剤が望まれてい
る。Therefore, there is a need for a transdermal preparation that can absorb a clinically effective amount of a drug while suppressing the occurrence of skin irritation.
（３）従来、経皮投与製剤を長時間貼付していると、当
然汚れてくるだけでなく、さらに自然に剥がれ、特にそ
の間に風呂にはいったりすると剥がれ易くなることが多
かった。(3) Conventionally, when a transdermal preparation is applied for a long period of time, it not only becomes dirty, but also tends to peel off naturally, especially if you take a bath during that time.
しかしながら、その都度貼り代えることは煩雑であるだ
けでなく、投与量を管理しにくくなったり、十分な薬効
が得られなかったり、また、外観上、衛生上の問題があ
った。However, changing the adhesive each time is not only troublesome, but also makes it difficult to control the dosage, does not provide sufficient medicinal efficacy, and poses problems in terms of appearance and hygiene.
そこで、長時間貼付していても汚染しにくく、かつ剥が
れにくい経皮投与製剤が望まれている。Therefore, there is a need for a transdermal preparation that is resistant to contamination and resistant to peeling off even when applied for a long period of time.
（４）経皮投与製剤は長時間持続型製剤であり、慢性の
疾患又は長期間の治療を要する疾患に特に有効である。(4) Transdermal preparations are long-lasting preparations and are particularly effective for chronic diseases or diseases requiring long-term treatment.
そしてかかる疾患の患者は高令の老人の比率が多い。A large proportion of patients with such diseases are elderly.
しかしながら、一般に老人は複雑な説明を要する取扱い
は不得意である。However, elderly people are generally not good at handling things that require complicated explanations.
そこで、単に吸収性等の点で製剤掌上満足される製剤で
あるだけでなく、患者にとって取扱い性に優れた経皮投
与製剤が望まれている。Therefore, there is a need for a transdermal preparation that is not only satisfactory in terms of absorbability and the like, but also has excellent handling properties for patients.
く課題を解決するための手段〉
本発明者らは従来からの経皮投与製剤の利点を活かしつ
つ、しかも皮膚カブレを減少させ、経皮吸収されにくい
薬物でも、できるだけ多く臨床有動量吸収させることが
でき、その上に取扱い性に優れた製剤のための方策につ
いて鋭意検討を重ねた結果、本発明に到達したものであ
る。Means for Solving the Problems> The present inventors have developed a drug that takes advantage of the advantages of conventional transdermal preparations, reduces skin irritation, and allows even drugs that are difficult to absorb transdermally to be absorbed in clinically active doses as much as possible. The present invention was arrived at as a result of extensive research into ways to create a formulation that is both easy to handle and easy to handle.
すなわち本発明は、
１、［Ｉ］１） フィルム状のバッキング層、２）
実質的に薬物不透過性で水蒸気透過性の薄膜層、および
３）薬物を含有する粘着剤層
とからなり該バッキング層、該薄膜層および該薬物を含
有する粘着剤層の順で、かつ該バッキング層と該薄膜層
が互いにそれらの一部または全面において粘着剤層を介
して積層せしめられてなる貼付用の製剤［Ｉ］、
［１］貼付用の製剤［１１において、さらに該バッキン
グ層と該薄膜層の間に通気性の面状体からなる層を設け
、該バッキング層と該通気性面状体からなる層、および
該通気性面状体からなる層と該薄膜層が互いにそれらの
一部または全部において粘着剤層を介して積層せしめら
れてなる貼付用の製剤［ＩＩ］、および
［ＩＩＩ］貼付用の製剤「工］または［コにおいて、該
バッキング層の自由となっている面の一部または全部に
面状支持体を該貼付用の製剤を貼付後に容易にとり除け
る程度の粘着力で積層せしめてなる貼付用の製剤［ＩＩ
Ｉ］
のいずれかの貼付用の製剤であって、該製剤の水分蒸散
性が１０ｍｇ／日・ｃｍ２以上である貼付用の製剤であ
る。That is, the present invention comprises: 1. [I] 1) a film-like backing layer; 2)
3) a thin film layer substantially impermeable to the drug and permeable to water vapor; and 3) an adhesive layer containing the drug, in the order of the backing layer, the thin film layer and the adhesive layer containing the drug; A patch preparation [I], [1] a patch preparation [11], in which a backing layer and the thin film layer are laminated with each other via an adhesive layer on a part or the entire surface thereof, further comprising the backing layer and the thin film layer. A layer consisting of an air-permeable planar body is provided between the thin film layers, and the backing layer and the layer consisting of the air-permeable planar body, and the layer consisting of the air-permeable planar body and the thin film layer are in contact with each other. In a patch preparation [II] which is partially or entirely laminated with an adhesive layer interposed therebetween, and [III] a patch preparation "technique" or "co", the free surface of the backing layer. A patch preparation [II
I] A preparation for patch application according to any one of the above, wherein the water transpiration property of the preparation is 10 mg/day/cm2 or more.
本発明の製剤は、その水分蒸散性が１０ｍｆ／′日・２
以上である。この値が１０ｍｇ／日・−に適しない場合
にあっては、皮膚に貼付したときのムレが著しく、その
結果カブレに影響する。カブレはこのようなムレ；製剤
の薬物や残留溶媒、粘着剤の種類等による化学的な刺激
；製剤構成成分による物理的刺激、例えば厚手剛直フィ
ルムを用いることによりエツジ部の刺激等が総合的に働
いて生ずる現象である。The formulation of the present invention has a water evaporation rate of 10mf/'day・2
That's all. If this value is not suitable for 10 mg/day.-, the skin will feel extremely stuffy when applied to the skin, resulting in rashes. Rash is caused by stuffiness; chemical irritation caused by the drug, residual solvent, type of adhesive, etc. in the formulation; physical irritation caused by the ingredients of the formulation; for example, by using a thick rigid film, irritation of the edges can be reduced comprehensively. It is a phenomenon that occurs during work.
本発明の水分蒸散性とは以下のようにして測定する。The moisture transpiration property of the present invention is measured as follows.
水分蒸散性の測定法
直径１２ｃｍの円形の原型ガラス板の中央部に、例えば
直径４（至）の円形、深さ０，６＞のくぼみを作り、そ
こに水を３ｍｌ入れる。十分な貼付しろを有する製剤を
その上に上記くぼみが製剤の中央部に来るように貼付し
、３７℃の通風条件に１日おいて、１日当たりの減量を
そのくぼみの上の部分の製剤の面積（上記の例では１２
．５６ｃＪ）で除し、水分蒸散性を測定する。Method for Measuring Moisture Evaporation In the center of a circular original glass plate with a diameter of 12 cm, a circular depression with a diameter of 4 (to) and a depth of 0.6> is made, and 3 ml of water is poured into it. A preparation with a sufficient adhesive area is pasted onto the preparation so that the depression is in the center of the preparation, and it is left in a ventilated condition at 37°C for one day, and the weight loss per day is determined by the weight loss of the preparation in the area above the depression. Area (12 in the example above)
．． 56cJ) to measure water transpiration.
本発明の貼付用の製剤は特定のフィルムをその一構成要
素とする。皮膚カブレを減少させるためには、まず第一
に製剤の物理的刺激を少なくすることが重要である。こ
のためには製剤のバッキングとして使用するフィルムの
厚みが小さい程刺激は減少するので、厚みは４．９μｍ
以下であるのが好ましく、特に４．０μｍ以下がこの傾
向が顕著となるので好ましい。しかし貼付用の製剤はヒ
トの皮膚に貼付して使用するので、ヒトの活動に伴うヒ
トの皮膚の伸縮運動にある程度追随できることが必要で
ある。あまりにｉ薄のフィルムは破断したり、あるいは
ほとんど追随しない場合は皮膚刺激が大きくなったりす
る。厚みを１．０μｍ以下に小さくしても、その物理的
刺激はあまり変わらなかったばかりか製造に不便になり
がちであるという不都合が増大する。。The adhesive preparation of the present invention has a specific film as one of its components. In order to reduce skin irritation, it is first important to reduce the physical irritation of the formulation. For this reason, the smaller the thickness of the film used as the backing for the formulation, the less irritation there will be, so the thickness is 4.9 μm.
It is preferable that the thickness is less than 4.0 μm, and it is particularly preferable that the thickness is 4.0 μm or less because this tendency becomes remarkable. However, since patch preparations are used by being applied to human skin, they need to be able to follow the expansion and contraction movements of human skin to some extent as a result of human activities. If the film is too thin, it may break, or if it hardly follows the surface, it may cause severe skin irritation. Even if the thickness is reduced to 1.0 .mu.m or less, the physical irritation does not change much, and the disadvantage that it tends to be difficult to manufacture increases. .
貼付剤にバッキングとしてフィルムを取付ける目的は貼
付部位の密封性を高めて経皮吸収を促進すること、粘着
層が露出されていると衣類や皮膚に粘着して管理に問題
があるため粘着面を被覆すること等のためである。しか
しながら、フィルムの厚み及びフィルムの材質はこの密
封性とも関わり、フィルムの厚みが小さくなる程密封性
も小さくなる。実際フィルムの厚みが５μｍ以上ではほ
とんど同じであり、５μｍ未満、なかでも４μｍ以下で
は厚みに相関して密封性が減少する傾向にある。The purpose of attaching a film as a backing to a patch is to improve the sealing of the application site and promote transdermal absorption. This is for covering etc. However, the thickness of the film and the material of the film are also related to this sealing performance, and the smaller the film thickness, the lower the sealing performance. In fact, when the thickness of the film is 5 μm or more, it is almost the same, and when it is less than 5 μm, especially 4 μm or less, the sealing performance tends to decrease in correlation with the thickness.
本発明においては、かかるフィルムは、さらに好ましく
は経時安定性が良好で、しかもヒト皮膚に貼付した場合
にアレルギー反応を起こしにくい等安全性の高いもので
あることが望ましい。かかるフィルムとしてはポリエチ
レン、ポリプロピレンのようなポリオレフィン；ポリエ
チレンテレフタレートやポリエチレンナフタレートのよ
うなポリエステル；ナイロン６やナイロン６６のような
ポリアミド；エチレン−酢酸ビニル共重合体等からなる
フィルムを用いることができる。これらのフィルムは単
体で用いてもよく、複合したりまた積層して用いてもよ
い。In the present invention, it is further desirable that such a film has good stability over time and is highly safe, such as being less likely to cause an allergic reaction when applied to human skin. As such a film, films made of polyolefins such as polyethylene and polypropylene; polyesters such as polyethylene terephthalate and polyethylene naphthalate; polyamides such as nylon 6 and nylon 66; ethylene-vinyl acetate copolymers, etc. can be used. These films may be used alone, or may be used in combination or in a laminated manner.
これらのフィルムのうち、ことにポリエステル、特にポ
リエチレンテレフタレートからなるフィルムが好ましい
。ポリエステルフィルムは、−船釣に熱や光に対する安
定性がよく、薬物の吸着や、薬物との相互作用が少なく
、またヒトに対する安全性が高い。さらに前記特定の厚
みなどのフィルムであっても適度の密封性を有するので
、即ち水分の透過性が適当で貼付剤を貼付した部位の皮
膚角質層の水分率が薬物の経皮吸収性を助けるのに十分
な量となるため、好ましい。Among these films, films of polyester, especially polyethylene terephthalate, are particularly preferred. Polyester film has good stability against heat and light for boat fishing, has little adsorption or interaction with drugs, and is highly safe for humans. Furthermore, even if the film has the above-mentioned specific thickness, it has appropriate sealing properties, that is, the moisture permeability is appropriate, and the moisture content of the stratum corneum of the skin at the site where the patch is applied helps the transdermal absorption of the drug. This is preferable because the amount is sufficient for
本発明の製剤は、薬物を含有する粘着剤層と前述のバッ
キング層の間に、実質的に薬物不透過性で水蒸気透過性
の薄膜層をその構成要素とする。The formulation of the present invention has a substantially drug-impermeable and water vapor-permeable thin film layer between the drug-containing adhesive layer and the above-mentioned backing layer.
該薄膜層は、皮膚側の粘着剤層中の薬物が実質的に透過
できない性質のため、製剤の貼付中に該皮膚側粘着剤層
中の薬物濃度を高く保ち、薬物の経皮性を高く維持でき
る効果がある。さらに皮膚側粘着剤層の全体量を低減で
きるので、製剤１枚当たりの薬物必要量を低く押さえる
ことができる。The thin film layer has a property that the drug in the adhesive layer on the skin side is substantially impermeable, so it maintains a high drug concentration in the adhesive layer on the skin side during application of the preparation and enhances the transdermal permeability of the drug. It has a sustainable effect. Furthermore, since the total amount of the skin-side adhesive layer can be reduced, the amount of drug required per preparation can be kept low.
そのため、本発明の製剤は高価な薬物やオピオイド系薬
物のような管理や取扱いに細心の配慮を要し、また規制
が厳しい薬物等の場合において顕著なる有用性を発揮で
きる。さらに前述の如く、薬物の透過拡散を実質的に阻
止するにもかかわらず水蒸気を透過させる性質は、貼付
用の製剤として実用に供するためにまず克服すべき大き
な課題である皮膚カブレの抑制に間して、それを解決す
る上で多大な効果を発揮する。Therefore, the preparation of the present invention can exhibit remarkable usefulness in the case of drugs that require careful management and handling, such as expensive drugs and opioid drugs, and drugs that are subject to strict regulations. Furthermore, as mentioned above, the property of allowing water vapor to pass through even though it substantially prevents the permeation and diffusion of drugs is effective in suppressing skin irritation, which is a major problem that must be overcome in order to be put to practical use as a patch preparation. It can be very effective in solving this problem.
該薄膜層は前述の性能を有し、かつ、厚みのできるだけ
薄いものが製剤全体の薄膜化のために有利であり、該薄
膜層を構成する材料の好適な例の一つとしては、厚み１
，０〜１．８μｍ程度のポリエステルフィルムが挙げら
れる。ポリエステル厚手フィルムの場合の透過性から理
論的に考えれば１６８μｍ程度の厚みでは充分な水蒸気
透過性が得られ難いと考えられるが、現実には目的に充
分な水蒸気透過性が得られたことは実に驚くべきことで
あった。これは、通常、ポリエステルフィルム中に添加
される滑り性向上剤等にきいんするボイド、ピンホール
等が有効に働いているとも推定される。It is advantageous for the thin film layer to have the above-mentioned performance and to be as thin as possible in order to make the entire formulation thin.One preferable example of the material constituting the thin film layer is a material with a thickness of 1.
, about 0 to 1.8 μm. Theoretically speaking, considering the permeability of thick polyester films, it would be difficult to obtain sufficient water vapor permeability with a thickness of approximately 168 μm, but in reality, sufficient water vapor permeability was obtained for the purpose. It was surprising. It is also presumed that this is due to the effective effect of voids, pinholes, etc. that occur in the slipperiness improver, etc., which are usually added to polyester films.
これに対して、厚み１２μｍや２５μｍといった厚手の
ポリエステルフィルムを用いた場合には、薬物の効果自
体は充分発揮されるが、一方貼付部分のムレのため、皮
膚が膨潤した感じになり、殊に貼付した製剤の縁部に沿
ってカブレを生ずることが多い。これは前述の水分だけ
でなく厚手フィルムのために物理的に皮膚が傷付けられ
たことにもよると推定される。On the other hand, when a thick polyester film with a thickness of 12 μm or 25 μm is used, the effect of the drug itself is sufficiently exhibited, but on the other hand, the skin feels swollen due to the stuffiness of the applied area, which is especially Rashes often occur along the edges of applied preparations. It is presumed that this is due not only to the above-mentioned moisture but also to the fact that the skin was physically damaged by the thick film.
かかる薄膜層の好適な他の例としては、極薄例えば０，
０５〜０．５μｍ程度のポリ−４−メチルペンテン−１
フイルムが挙げられる。Other suitable examples of such thin film layers include extremely thin films such as 0,
Poly-4-methylpentene-1 of about 0.05 to 0.5 μm
Film is an example.
かかる極薄フィルムはその構成部分の透過性の違いに応
じて、圧力差を利用して空気を透過させることにより空
気一部の成分、例えば酸素や炭酸ガス、あるいは水蒸気
を濃縮し得ることが知られている。この他にも好適な例
をあげれば、枚挙のいとまがないが、要するに薬物を実
質的に透過せずヒトの皮膚からの水分蒸散性を妨げてし
まわないものであれば良いのである。さらに言えば、フ
ィルムの厚みが余りに大きいと皮膚に貼付した際、種々
のこすれのためにひっかかりを生じ、剥がれやすい傾向
がある。これらとともに製造上の許容性等を配慮すべき
であるが、４．９μｍ以下が適当である。It is known that such an ultra-thin film can concentrate some components of the air, such as oxygen, carbon dioxide, or water vapor, by allowing air to pass through it using pressure differences, depending on the permeability of its constituent parts. It is being There are other suitable examples, too numerous to mention, but in short, any material is suitable as long as it does not substantially permeate the drug and does not impede water evaporation from human skin. Furthermore, if the film is too thick, when it is applied to the skin, it tends to get caught due to various types of rubbing and is likely to peel off. In addition to these considerations, manufacturing tolerances should be taken into consideration, but a thickness of 4.9 μm or less is appropriate.
該バッキング層、該薄膜層は粘着剤層によりその一部ま
たは全部にわたってつながれる。粘着剤層に関して特に
制限はないが安全上、人体に適用が許容されるものであ
るべきである。またその厚みは粘着力の面から支障のな
い範囲で薄い方が、製剤全体の厚みを減じ、ひっかかり
による剥がれを防ぐ上で好ましい。一般には２０μｍ以
下、殊に１０μｍ以下で充分なことが多い。また上述の
如き層状物のバッキング層と反対側には、医薬品として
の機能の本体である薬物を含有する粘着剤層を設ける。The backing layer and the thin film layer are connected over part or all of them by an adhesive layer. There are no particular restrictions on the adhesive layer, but for safety reasons it should be acceptable for application to the human body. In addition, it is preferable that the thickness be as thin as possible without causing any problems in terms of adhesive strength, in order to reduce the overall thickness of the preparation and prevent it from peeling off due to snagging. Generally, a thickness of 20 μm or less, particularly 10 μm or less is often sufficient. Further, on the side opposite to the backing layer of the above-mentioned layered product, an adhesive layer containing a drug, which is the main function of the drug, is provided.
該粘着剤層も粘着性の面から支障のない範囲で薄い程好
ましいが、一方薬用量が該粘着剤と薬物との相溶性も考
慮されるべきである。一般には５〜３０μｍ程度になる
ように貼付面積の面からの兼ね合いをも考慮して、設計
するのが好ましい。貼付面積に間して言えば薬物の種類
と粘着剤の種頴によってその溶解性や経皮吸収性等が変
動し、充分な経皮吸収性を確保するために貼付面積を大
きくする結果になる場合がある。しかし、人体において
許容される貼付面積には当然のことながら限界があり、
むやみに大きな面積をとれないし、面積を増大させるこ
とは薬剤量を増大させることとなり、必要最小限に留め
るべきでありことは論を待たない。通常５〜２０□−程
度の範囲にするのが取扱いやすく好ましいといえる。The adhesive layer is preferably as thin as possible from the viewpoint of adhesiveness, but the compatibility of the adhesive with the drug should also be taken into consideration when determining the dosage. Generally, it is preferable to design the thickness to be approximately 5 to 30 μm, taking into consideration the bonding area. Regarding the area of application, the solubility and transdermal absorbability vary depending on the type of drug and the type of adhesive, so the area of application must be increased to ensure sufficient transdermal absorption. There are cases. However, there are naturally limits to the permissible application area on the human body.
It goes without saying that an unnecessarily large area cannot be taken, and increasing the area will increase the amount of drug, so it should be kept to the minimum necessary. Generally, it is preferable to keep it in the range of about 5 to 20 square meters for ease of handling.
本発明にあっては、その水分蒸散性を適当な程度に設定
する目的で、該バッキング層と該薄膜層の間に通気性の
面状体からなる層を置くことも有用であり、好ましい態
様である。かかる通気性の面状体の層は、例えば繊維の
織・ｗｌ物、不織布。In the present invention, it is also useful to place a layer made of an air-permeable planar body between the backing layer and the thin film layer in order to set the water evaporation property to an appropriate level, and a preferred embodiment It is. The layer of such a breathable planar body is, for example, a woven or woven fabric of fibers or a non-woven fabric.
紙状物１通気性日多孔フィルムの一種またはそれ以上の
組合せが考えられる。繊維の材質としてはナイロン、ポ
リエステル、アクリル、ウレタン・等の合成繊維、綿等
の天然繊維、レーヨン、アセテート等の半合成繊維等を
単一でまたは複合して用いることができる。特に繊維面
状体が外周方向に貫通した孔を有する中空繊維からなる
編物であるとき、好ましい結果を与える。A combination of one or more of the paper-like materials 1, breathable and porous films is contemplated. As the material of the fibers, synthetic fibers such as nylon, polyester, acrylic, urethane, etc., natural fibers such as cotton, semi-synthetic fibers such as rayon, acetate, etc. can be used singly or in combination. Particularly favorable results are obtained when the fibrous sheet body is a knitted fabric made of hollow fibers having holes penetrating in the outer circumferential direction.
ここで外周方向に貫通した孔を有する中空繊維としては
、中空繊維断面全体に散在し、繊維軸方向に配列しかつ
その少なくとも一部は中空部まで連通している微細孔を
有する中空繊維が好ましい。Here, the hollow fibers having holes penetrating in the outer circumferential direction are preferably hollow fibers having fine holes scattered over the entire cross section of the hollow fibers, arranged in the fiber axis direction, and at least a part of which communicates with the hollow part. .
本発明の中空繊維の横断面における外形および中空部の
形状はいずれも任意でよい。例えば外形および中空部が
いずれもほぼ円形の場合、外形および中空部のいずれか
一方がほぼ円形で他方が異形の場合、外形および中空部
共の類似または非類似の異形の場合等であってもよい。Both the outer shape and the shape of the hollow portion in the cross section of the hollow fiber of the present invention may be arbitrary. For example, if both the outer shape and the hollow part are approximately circular, if one of the outer shape and the hollow part is approximately circular and the other is an irregular shape, or if the outer shape and the hollow part are both similar or dissimilar irregular shapes, etc. good.
また、外形の大きさについては特に制限する必要はない
。Further, there is no need to particularly limit the size of the external shape.
かかる中空繊維の太さは直径４〜４５μｍが望ましい。The thickness of such hollow fibers is preferably 4 to 45 μm in diameter.
太さが４５μｍ以上となると皮膚刺激が多すぎる。また
４μｍ以下のものは取扱い性が悪い。If the thickness is 45 μm or more, there will be too much skin irritation. Moreover, those with a diameter of 4 μm or less are difficult to handle.
本発明の中空繊維の中空率は任意でよいが、特に５％以
上であることが好ましく、また外周方向に貫通した孔の
繊維横断面積に占める割合は、中空部分を除いた繊維横
断面積の０．０１〜７０％が好ましく、特に０．０１〜
５０％、さらに１〜５０％が好ましい
本発明においては、かかる中空繊維は編物の形態である
ことを要する。かかる編物は、主として前述の中空繊維
から構成されていればよく、本発明の目的とする効果が
損なわれない限りにおいてそのような中空繊維以外の繊
維が一部混入されていてもよい。The hollowness ratio of the hollow fibers of the present invention may be arbitrary, but it is particularly preferably 5% or more, and the ratio of holes penetrating in the outer circumferential direction to the cross-sectional area of the fibers is 0% of the cross-sectional area of the fibers excluding the hollow portions. .01 to 70% is preferable, especially 0.01 to 70%.
In the present invention, where the content is preferably 50%, and more preferably 1 to 50%, such hollow fibers are required to be in the form of a knitted fabric. Such a knitted fabric may be mainly composed of the above-mentioned hollow fibers, and a portion of fibers other than such hollow fibers may be mixed as long as the desired effects of the present invention are not impaired.
ところで繊維の形態としては大きく分けて織物、編物、
不織布があり、従来衣料用に使用されているガーゼ、絆
創膏等の基材は織物である。これは織物の寸法安定性が
よく、取扱い易いことが主な理由と考えられる。しかし
織物は貼付剤にしなとき皮膚刺激が大きい。これに対し
て編物は皮膚刺激がより少なく、特に外周方向に貫通し
た孔を有する中空繊維からなる薄い編物は極めて柔軟で
ありほとんど皮膚刺激を生じない。驚くべきことにこの
編物に伸縮性の少ない薄い膜を積層しても柔軟性はほと
んど失われない。これは編物のもつ微妙な繊維組織内の
余裕が外部応力を吸収するためと考えられる。By the way, the forms of fiber can be broadly divided into woven fabrics, knitted fabrics,
There are nonwoven fabrics, and the base materials of gauze, bandages, etc. conventionally used for clothing are woven fabrics. The main reason for this is thought to be that the woven fabric has good dimensional stability and is easy to handle. However, textiles can cause serious skin irritation when used as a patch. On the other hand, knitted fabrics cause less skin irritation, and in particular, thin knitted fabrics made of hollow fibers having holes penetrating in the outer circumferential direction are extremely flexible and cause almost no skin irritation. Surprisingly, even if this knitted fabric is laminated with a thin film with little stretch, there is almost no loss of flexibility. This is thought to be because the delicate allowance within the fiber structure of the knitted fabric absorbs external stress.
中空繊維を構成する材質としては薬物との相互作用が実
質的に無く、安全性に優れ、安全性上も優れたポリエチ
レンテレフタレートが特に望ましい。As the material constituting the hollow fibers, polyethylene terephthalate is particularly desirable because it has virtually no interaction with drugs and is highly safe.
本発明で用いるポリエチレンテレフタレートの中空繊維
は、例えば、特開昭５６−２０６１２号公報、特開昭５
６−２０６１３号公報、特開昭５６−４３４２０号公報
等に記載された方法によって製造することができる。The hollow fibers of polyethylene terephthalate used in the present invention are disclosed in, for example, JP-A-56-20612, JP-A-5
It can be produced by the methods described in JP-A No. 6-20613, JP-A-56-43420, and the like.
驚くべきことに本発明においては繊維面状体を積層した
貼付剤にすることによって、かかる貼付剤を貼付した患
者の置かれる外的環境や運動状態により皮膚発汗の程度
が多少変化しても、貼付部位の皮膚角層の水分率をほと
んど充分、かつ同じ値に保つことができ、しかして皮膚
刺激を大幅に減少し得たのである。Surprisingly, in the present invention, by creating a patch in which fibrous planar bodies are laminated, even if the degree of skin sweating changes somewhat depending on the external environment or exercise condition of the patient to whom the patch is applied, The moisture content of the stratum corneum of the skin at the application site could be kept almost at a sufficient level and at the same value, thus significantly reducing skin irritation.
かかる通気性の面状体の層は、該バッキング材および該
薄膜層と、それぞれその一部または全面にわたって、同
一もしくは互いに異なる粘着剤層によってつながれる。The layer of the air-permeable planar body is connected to the backing material and the thin film layer, respectively, over a portion or the entire surface thereof, by the same or different adhesive layers.
この場合の粘着剤層も必要な粘着性を確保する範囲にお
いて薄いものである方が好ましいのはいうまでもない。Needless to say, it is preferable that the adhesive layer in this case be as thin as possible to ensure the necessary adhesiveness.
本発明において、かかる各層に用いちれる粘着剤層はヒ
トへの安全性や、経時的な安全性にすぐれ、かつ薬剤や
その他の各構成成分との不適当な副反応を生じないもの
であれば各々独立に従来公知のものを適当に選択すれば
よい。その好適な例は一般にアクリル系粘着剤と称され
ているものが挙げられるが、これに限定されるものでは
ない。In the present invention, the adhesive layer used for each layer must be one that has excellent safety to humans and safety over time, and that does not cause inappropriate side reactions with drugs or other constituent components. In this case, each may be independently and appropriately selected from conventionally known ones. Suitable examples include what is generally called an acrylic adhesive, but the adhesive is not limited thereto.
本発明の貼付用の製剤に適用できる薬物は基本的に経皮
吸収される薬物であることが前提とされるが、本発明の
目的からいえば殊に薬用量の比較的少ない薬物に好適で
ある。その例はオピオイド系薬物、エストロゲン系薬物
、プロゲスチン系薬物等を挙げることができる。勿論、
これらに限定されるものではないことは言うまでもない
。It is assumed that drugs applicable to the patch preparation of the present invention are basically drugs that are absorbed through the skin, but from the purpose of the present invention, it is particularly suitable for drugs with relatively small doses. be. Examples include opioid drugs, estrogen drugs, progestin drugs, and the like. Of course,
Needless to say, it is not limited to these.
本発明にあっては、該バ・・ｌキング層の自由となって
いる面に、その一部または全面にとりつけられており、
製剤を貼付後、容易にとり除き得るようにした面状の支
持体をとりつけである貼付用の製剤も特に好ましい態様
として含まれる。かかる支持体を用いることにより殊に
貼付しやすさが顕著に向上することが見出された。In the present invention, it is attached to a part or the entire surface of the free surface of the backing layer,
Particularly preferred embodiments also include preparations for patching, in which a planar support is attached so that the preparation can be easily removed after application. It has been found that the use of such a support significantly improves the ease of application.
かかる支持体は、原則としてまず本発明の製剤をヒトの
皮膚に貼付し、しかるのちにとり除いて、製剤［Ｉ］ま
たは［ＩＩ］のみを残すためのものである。In principle, such a support is used to first apply the preparation of the present invention to human skin and then remove it, leaving only the preparation [I] or [II].
このようにすることにより製剤を取扱うときは、この支
持体のかたさのなめに製剤かカールしなり、破れなりす
ることがなく、患者は容易に局部に貼付することができ
る。局部に貼付後はこの面状の支持体を取り除くので、
貼付中は本発明の各構成体層の特徴が十分に発揮され、
皮膚カブレを軽減する等の諸口的が達成されるのである
。By doing this, when handling the preparation, the preparation will not curl or tear due to the hardness of the support, and the patient can easily apply it to the local area. After applying to the local area, this planar support is removed.
During application, the characteristics of each constituent layer of the present invention are fully exhibited,
Many benefits such as reducing skin irritation can be achieved.
本発明においては極めて薄いフィルムを使用するため、
かかる支持体とバッキング層の付着力が重要である。Since an extremely thin film is used in the present invention,
The adhesion between the support and the backing layer is important.
支持体とバッキング層との付着力があまりに大きいと支
持体をバッキング層から外すに際してバッキング層が破
れたり、製剤が眉間剥離を起したり、製剤が皮膚から剥
がれなりする問題を生じやすい。本発明者の検討結果に
よれば、支持体とバッキング層との付着力が該バッキン
グ層と粘着剤層を介する製剤の各層との間の付着力より
小であることが重要である。If the adhesion between the support and the backing layer is too strong, problems such as the backing layer being torn when the support is removed from the backing layer, the formulation peeling off between the eyebrows, and the formulation peeling off from the skin are likely to occur. According to the study results of the present inventors, it is important that the adhesive force between the support and the backing layer is smaller than the adhesive force between the backing layer and each layer of the formulation via the adhesive layer.
更に具体的には、支持体とバッキング層の付着力が２０
ｇ／１２ｃ！ｌを超えると支持体をバッキング層から外
すときにバッキング層の方が破断し易くなる。理屈の上
からはフィルムの強度が８〜８５ｇ、／■であるとき、
付着力は３〜２０ｇ／１２ｃｍを超えて、例えば２４ｇ
／１２ｃｘ、即ち単位幅である１ａｍ当り８ｇであって
も、フィルムは破れないと考えられるが、実際の製剤で
は付着力が２０ｇ／１２優を超えると、フィルム破れが
発生しなり、製剤がヒトの皮膚から剥がれたりするので
ある。また３ｇ／１２ａｎ未満であると製造中、保管中
、又は取扱中に支持体とバッキング層の眉間が剥離して
しまい所望の目的を達成することができない。したがっ
て好ましい付着力は３ｇ／１２ｃｍ乃至２０ｇ％’１２
個である。More specifically, the adhesion between the support and the backing layer is 20
g/12c! If it exceeds l, the backing layer will be more likely to break when the support is removed from the backing layer. Theoretically, when the strength of the film is 8 to 85 g, /■,
The adhesion force is 3-20g/12cm or more, e.g. 24g
/12cx, that is, 8 g per 1 am of unit width, it is thought that the film will not tear, but in actual formulations, if the adhesion force exceeds 20 g/12 cx, film tearing will occur, and the formulation will not be suitable for humans. It may peel off from the skin. Moreover, if it is less than 3 g/12 an, the glabella of the support and the backing layer will peel off during production, storage, or handling, making it impossible to achieve the desired purpose. Therefore, the preferred adhesion force is 3g/12cm to 20g%'12
It is individual.
本発明で言う付着力とは、バッキング層と好ましくは適
当な糊剤を介してバッキング層にとりつけられた支持体
とを１２ａｎ幅のスリット状に裁断し、支持体又はバッ
キングを９０°の方向に３０ｃｍ／分の速度で引き剥が
す時の荷重（ｇｒ）をいう。バッキングと支持体がスリ
ット状や点状で部分的に付着させであるときは、付着し
た部分の引き剥がす時の荷重（ｇｒｌを測定し、その値
を幅１２ｃｓｎ相当に換算した値とする。Adhesion in the present invention refers to cutting the backing layer and the support attached to the backing layer preferably through a suitable adhesive into a slit shape with a width of 12an, and cutting the support or backing in a 90° direction. This refers to the load (gr) when peeling off at a speed of 30 cm/min. When the backing and the support are partially attached in the form of slits or dots, the load (grl) when peeling off the attached part is measured and the value is converted to a value equivalent to a width of 12csn.
本発明においては、面状の支持体の腰の強さを調節する
ことにより、さらに好ましい製剤とすることができる。In the present invention, a more preferable formulation can be obtained by adjusting the stiffness of the planar support.
面状支持体の腰の強さは、例えばＪＩＳ Ｐ−８１４３
のこわさ試験方法によりこわさ（■３、／１００ ）と
してあられすことかできるが、好ましくはこわさが０．
０８以上、さらに好ましくは０１２７以上である。The stiffness of the planar support is determined by, for example, JIS P-8143.
The stiffness can be measured as (■3, /100) according to the stiffness test method, but preferably the stiffness is 0.
08 or more, more preferably 0127 or more.
面状の支持体の基材としては、ポリエチレン。The base material for the planar support is polyethylene.
ポリプロピレンのようなポリオレフィン；ポリエチレン
テレフタレートやポリエチレンナフタレートのようなポ
リエステル；ナイロン６やナイロン６６のようなポリア
ミド；エチレン−酢酸ビニル共重合体；ポリビニルアル
コールなどからなるフィルム、不織布７紙状物、織編物
、微多孔フィルム等を用いることができる。また綿、ア
セテート等の天然又は再生の通常の衣料用織編物も用い
ることができる。Polyolefins such as polypropylene; polyesters such as polyethylene terephthalate and polyethylene naphthalate; polyamides such as nylon 6 and nylon 66; ethylene-vinyl acetate copolymers; films, non-woven fabrics, paper-like materials, woven and knitted fabrics such as polyvinyl alcohol. , microporous film, etc. can be used. Also, natural or recycled ordinary woven or knitted fabrics for clothing, such as cotton or acetate, can also be used.
かかるフィルム、不織布、１ｍ編物等からなる面状の支
持体の基材とバッキング層との付着は、かかる支持体の
基材とバッキング層のいずれか、又は両方を必要に応じ
加熱下に加圧する方法５面状の支持体とバッキング層を
粘着剤や糊剤のような接着性物質を用いておこなうこと
ができる。The backing layer is attached to the base material of the planar support made of such a film, nonwoven fabric, 1 m knitted fabric, etc., by applying pressure to either or both of the base material of the support body and the backing layer while heating as necessary. Method 5 The support and backing layer can be formed using an adhesive material such as an adhesive or a glue.
特に面状の支持体の基材として織！ｉ物を用い、接着性
物質としてポリビニルアルコール、酢酸ビニル ポリビ
ニルピロリドン、アクリル系共重合物、ソルビトール、
デンプン等の接着物質を用いるとき良好な結果が得られ
やすい。Woven especially as a base material for planar supports! Polyvinyl alcohol, vinyl acetate, polyvinylpyrrolidone, acrylic copolymer, sorbitol,
Good results tend to be obtained when using adhesive substances such as starch.
この面状の支持体は製剤の取扱い時にバ・ンキング層に
付着しており、ヒト皮膚に製剤を貼付した後は必要に応
じて取り除いて用いられる。しかしながら製剤は、保存
中はアルミ袋等に密封しておくために、若し面状の支持
体とバッキング層との付着に使用した接着物質の使用溶
媒であるメタノール、酢酸エチルや水等が残存すると、
これらの残存溶媒は製剤の保存中に、薬物を含有した粘
着層の中にも移動、拡散して含まれるようになりやすい
。そのため皮膚カブレの発生や薬物の経時安定性の低下
につながることがある。This planar support is attached to the banking layer during handling of the preparation, and is removed as necessary after the preparation is applied to human skin. However, since the formulation is sealed in an aluminum bag or the like during storage, methanol, ethyl acetate, water, etc., which are the solvents used for the adhesive substance used to attach the planar support to the backing layer, may remain. Then,
These residual solvents tend to migrate and diffuse into the drug-containing adhesive layer during storage of the preparation. This may lead to the occurrence of skin irritation and a decrease in the stability of the drug over time.
このような不都合を除くためには面状の支持体とバッキ
ング層の付着に使用した溶媒等が残留しないようにすべ
きであるが、面状の支持体がフィルムからなる場合は溶
媒等の完全な除去が難しく、生産方法に特別の工夫を要
する。この場合、本発明の製剤は特定のフィルムをバッ
キングとして用いているため、複雑な工程をとると、フ
ィルムが破断したり、しわがはいったりして生産効率が
低下しがちである。しかし、面状の支持体が例えば織編
物の如き貫通孔を有するものの場合、溶媒等の蒸気が簡
単にそこから逃げるため、極めて簡単に溶媒等を除去で
きるのである。In order to eliminate such inconveniences, it is necessary to ensure that the solvent used to attach the planar support and the backing layer does not remain, but if the planar support is made of a film, it is necessary to completely remove the solvent, etc. It is difficult to remove and requires special ingenuity in production methods. In this case, since the formulation of the present invention uses a specific film as a backing, if the process is complicated, the film tends to break or wrinkle, reducing production efficiency. However, if the planar support has through-holes, such as a woven or knitted material, the vapor of the solvent and the like can easily escape therethrough, so that the solvent and the like can be removed very easily.
特に織編物等からなる面状の支持体とバッキングを合せ
、織編物等の上から接着物質の溶液を加えて、しかるの
ち加熱することで面状の支持体とバッキングは残留溶媒
の心配もなく十分に付着することができる。また、あら
かじめ織編物等からなる面状の支持体に接着物質を付着
させておき乾燥後、又はそのままでバッキング層に付着
させ、必要に応じて残留溶媒を除くために加熱や風乾す
る方法等が採用できる。In particular, by combining a planar support made of a woven or knitted fabric with a backing, adding an adhesive solution over the woven or knitted fabric, and then heating, the planar support and backing can be bonded together without worrying about residual solvent. Can be adhered well. Alternatively, an adhesive substance may be attached in advance to a planar support made of woven or knitted fabric, etc., and then it may be attached to the backing layer after drying or as it is, and then heated or air-dried to remove residual solvent as necessary. Can be adopted.
本発明においては前述のバッキング層および／または薄
膜層としてポリエステルフィルムを用いるのが好ましい
。その場合、通常、公知のようにポリエステルフィルム
中にはその滑り性を改良する目的で少割合の固型微粒子
を存在させるが、本衣料品用途にどのような特性が必要
であるかについて、充分な知見はなかっな。In the present invention, it is preferable to use a polyester film as the above-mentioned backing layer and/or thin film layer. In that case, as is well known, a small proportion of solid fine particles are usually present in the polyester film for the purpose of improving its slipperiness, but it is necessary to fully understand what characteristics are required for this clothing application. I don't have any knowledge.
本発明者はかかる点について種々検討の結果、該ポリエ
ステルフィルム層に存在する固型微粒子量が０．０１〜
１重量％であり、その平均粒子径が０．０１〜１μｍで
あり、かつ該平均粒子径が実質的にポリエステルフィル
ムの厚みの１．５倍を超えないことが重要であることを
見出した。As a result of various studies regarding this point, the present inventor found that the amount of solid fine particles present in the polyester film layer is 0.01 to
It has been found that it is important that the average particle size is 1% by weight, that the average particle size is 0.01 to 1 μm, and that the average particle size does not substantially exceed 1.5 times the thickness of the polyester film.
該固型微粒子は、■二酸化硅素、■アルミナ、■二酸化
硅素分を３０重量％以上含有する硅酸塩。The solid fine particles are 1) silicon dioxide, 2) alumina, and 2) a silicate containing 30% by weight or more of silicon dioxide.
アルミノシリケート化合物、■マグネシウム、亜鉛、ジ
ルコニウム、チタンから選ばれる一種以上の金属の酸化
物、■カルシウム、バリウムから運ばれる一種以上の金
属の硫酸塩、■リチウム、ナトリウム、カルシウムから
選ばれる一種以上の金属の燐酸塩、■リチウム、ナトリ
ウム、カリウムから選ばれる一種以上の金属の安志香酸
、■カルシウム、バリウム、亜鉛、マンガンから選ばれ
る一種以上の金属のテレフタル酸塩、■マグネシウム、
カルシウム、バリウム、鉄、コバルト、マンガン、ニッ
ケル等から選ばれる一種以上の金属のチタン酸塩、■カ
ルシウム、マグネシウムから選ばれる一種、Ｏ炭素、Ｏ
ガラス、Ｏ架橋化ポリスチレンの如き無機あるいは有機
の固体微粒子を例示できる。勿論、これらの使用は一種
又は二種以上の混合であってもよい。Aluminosilicate compounds; ■Oxides of one or more metals selected from magnesium, zinc, zirconium, and titanium; ■Sulfates of one or more metals carried from calcium and barium; ■One or more metal oxides selected from lithium, sodium, and calcium. Phosphates of metals, ■Benzioic acids of one or more metals selected from lithium, sodium, and potassium; ■Terephthalates of one or more metals selected from calcium, barium, zinc, and manganese; ■Magnesium;
titanate of one or more metals selected from calcium, barium, iron, cobalt, manganese, nickel, etc., one selected from calcium, magnesium, O carbon, O
Examples include inorganic or organic solid fine particles such as glass and O-crosslinked polystyrene. Of course, these may be used alone or in combination of two or more.
かかる微粒子量が０．０１重量％に満たない範囲にあっ
ては、滑り性が悪いため好ましくなく、また１重量％を
超える範囲にあっては薬物の経皮吸収性が充分満足され
なくなる場合を生じたりして製剤として好ましくなくな
る。またその平均粒子径が０，０１μｍに満たない範囲
のものにあっては滑り性が不充分で取扱い性が充分満足
されず、また１μｍを超えたりフィルムの厚みの１．５
倍を超える範囲にあっては、前述と同様に薬物の経皮吸
収性が充分満足されない場合を生ずる。これはかかる場
合にあっては、該粒子とフィルム素材の間のボイド等に
起因して水分蒸散性や通気性が大きくなりすぎるなめで
はないかとも考えられる。If the amount of such fine particles is less than 0.01% by weight, it is undesirable because of poor slipperiness, and if it exceeds 1% by weight, the transdermal absorption of the drug may not be sufficiently satisfied. This makes it undesirable as a drug product. In addition, if the average particle diameter is less than 0.01 μm, the slipperiness will be insufficient and the handling property will not be fully satisfied;
If the range is more than twice that, the transdermal absorption of the drug may not be fully satisfied, as described above. In such a case, it is considered that the water evaporability and air permeability become too large due to voids between the particles and the film material.
本発明を構成する各層を積層する方法・順序に特に制限
はない。各層や薬物等の性質を考慮しつつ適宜実施すれ
ばよく、本発明の範囲に属するものである。There are no particular restrictions on the method or order in which the layers constituting the present invention are laminated. It may be carried out as appropriate while taking into consideration the properties of each layer, drug, etc., and is within the scope of the present invention.
以上に詳述した如く、本発明は経皮吸収に適した薬物を
投与する剤型として極めて優れた特長を有するものであ
る。As detailed above, the present invention has extremely excellent features as a dosage form for administering drugs suitable for transdermal absorption.
〈実施例〉
以下に実施例を掲げて本発明の効果を更に詳細に述べる
。<Example> The effects of the present invention will be described in more detail with reference to Examples below.
実施例１および比較例１
１） フィルム状バッキング層として厚み１．８μｍの
ポリエステルフィルム、
２）薄膜層として厚み１．３μｍのポリエステルフィル
ム、および
３） 薬物としてプロゲステロンを１．３ｇ、／’ｄの
割合で含む１０μｍの厚みのアクリル系粘着剤層とから
なり、１）〜３）の順でかつ該バッキング層と薄膜層を
それらの全面にわたってアクリル系の厚み１０ｕ ｍの
粘着剤層を介して積層せしめて貼付用の製剤［Ｉ］を作
成しな。Example 1 and Comparative Example 1 1) A polyester film with a thickness of 1.8 μm as a film-like backing layer, 2) A polyester film with a thickness of 1.3 μm as a thin film layer, and 3) Progesterone as a drug at 1.3 g/'d. The backing layer and the thin film layer are laminated in the order of 1) to 3) with an acrylic adhesive layer having a thickness of 10 μm interposed over the entire surface thereof. At least create a patch preparation [I].
この貼付用の製剤に使用したポリエステルフィルムには
、平均粒径０．７μｍの剛性シリカ０．０９重量％が含
まれている。このポリエステルフィルムを用いた製剤の
水分蒸散性を既述の方法で測定した結果、１７．２ｍｇ
／日・−であった。The polyester film used in this adhesive preparation contains 0.09% by weight of rigid silica with an average particle size of 0.7 μm. As a result of measuring the water evaporation property of the formulation using this polyester film using the method described above, it was found that 17.2 mg
It was /day・-.
なお、比較のために厚さ１２μｍのポリエステルフィル
ムに、実施例１に使用したと同じ厚さ１０μｍで、かつ
プロゲステロンを含有する粘着剤層と貼り合わせた製剤
を作成したく比較例１）。For comparison, we wanted to create a preparation in which a 12-μm-thick polyester film was laminated with an adhesive layer having the same thickness of 10 μm as used in Example 1 and containing progesterone (Comparative Example 1).
この製剤の水分蒸散性は７．３ｍｇ／日・−にすぎなか
った。The water transpiration rate of this preparation was only 7.3 mg/day.
実施例２
実施例１におけるバッキング層と薄膜層の間に通気性の
面状体からなる層としてポリエステル中空微多孔系編物
を用い、これら三層を各々１０μｍの厚みのアクリル系
粘着剤層で積層した。得られた層状物の薄膜層の上に、
実施例１に用いた薬物を含有する粘着剤層を積層して一
つの貼付用の製剤［ＩＩ］とした。Example 2 A hollow microporous polyester knitted fabric was used as a layer consisting of a breathable planar body between the backing layer and the thin film layer in Example 1, and these three layers were laminated with an acrylic adhesive layer each having a thickness of 10 μm. did. On top of the thin film layer of the resulting layered product,
The drug-containing adhesive layers used in Example 1 were laminated to form one adhesive preparation [II].
この製剤の水分蒸散性は１９．４■７／日・−であった
。The water evaporation rate of this preparation was 19.4 7/day.
試験例
本発明の効果を更に明確にするため、実施例１２および
比較例１の製剤を７．１α角の大きさにし、ヒトの右胸
部に各２人ずつ４８時間貼付し、除剤後１時間の状態を
観察した。その結果を表−１に示した。Test Example In order to further clarify the effects of the present invention, the preparations of Example 12 and Comparative Example 1 were made into a size of 7.1 α angle and applied to the right chest of two people for 48 hours. I observed the state of time. The results are shown in Table-1.
本発明の構造を有する製剤は貼付前後において皮膚状態
に実質的な変化を生じることがなく、優れた製剤である
ことが明らかとなった。It has been revealed that the preparation having the structure of the present invention causes no substantial change in the skin condition before and after application, and is an excellent preparation.
Claims (1)
的に薬物不透過性で水蒸気透過性の薄膜層、および３）
薬物を含有する粘着剤層とからなり該バッキング層、該
薄膜層および該薬物を含有する粘着剤層の順で、かつ該
バッキング層と該薄膜層が互いにそれらの一部または全
面において粘着剤層を介して積層せしめられてなる貼付
用の製剤［ I ］、 ［II］貼付用の製剤［ I ］において、さらに該バッキ
ング層と該薄膜層の間に通気性の面状体からなる層を設
け、該バッキング層と該通気性面状体からなる層、およ
び該通気性面状体からなる層と該薄膜層が互いにそれら
の一部または全部において粘着剤層を介して積層せしめ
られてなる貼付用の製剤［II］、および ［III］貼付用の製剤［ I ］または［II］において、該
バッキング層の自由となっている面の一部または全部に
面状支持体を該貼付用の製剤を貼付後に容易にとり除け
る程度の粘着力で積層せしめてなる貼付用の製剤［III
］ のいずれかの貼付用の製剤であって、該製剤の水分蒸散
性が１０ｍｇ／日・ｃｍ＾２以上である貼付用の製剤。 ２、該バッキング層がその厚さが０．５〜４．９μｍの
ポリエステルフィルムである請求項１記載の貼付用の製
剤。 ３、該薄膜層が、その厚さが２μｍ以下のポリエステル
フィルムである請求項１記載の貼付用の製剤。 ４、該薬物を含有する粘着剤層が、アクリル系粘着剤か
らなる請求項１記載の貼付用の製剤。 ５、請求項２又は請求項３に記載の該ポリエステルフィ
ルムが、そのフィルム層中の存在する固型微粒子量が０
．０１〜１重量％であり、その平均粒子径が０．０１〜
１μｍで、かつ該平均粒子径が実質的に該ポリエステル
フィルムの厚みの１．５倍を超えないポリエステルフィ
ルムである貼付剤。 ６、該粘着剤がアクリル系樹脂からなる粘着剤である請
求項１〜５いずれか１項記載の貼付剤。 ７、該薬物が硝酸イソソルビド、ニトログリセリン、ブ
プレノルフィン、エストラジオール、プロゲステロン、
ケトチフェン、ビンポセチン、ニコチン及びそれらの誘
導体から選ばれる１種又は２種以上の薬物である請求項
１〜６いずれか１項記載の貼付剤。[Claims] 1. [I] 1) a film-like backing layer, 2) a thin film layer substantially impermeable to drugs and permeable to water vapor, and 3)
an adhesive layer containing a drug; the backing layer, the thin film layer, and the drug-containing adhesive layer are arranged in this order, and the backing layer and the thin film layer each have an adhesive layer on a part or the entire surface thereof; [I], [II] In the patch preparation [I], the patch preparation [I] is further provided with a layer consisting of an air-permeable planar body between the backing layer and the thin film layer. , a layer consisting of the backing layer and the air-permeable planar body, and a layer consisting of the air-permeable planar body and the thin film layer, some or all of which are laminated to each other via an adhesive layer. [II], and [III] In the preparation [I] or [II], a planar support is provided on part or all of the free surface of the backing layer. Patch preparation [III
] The preparation for patch use according to any one of the following, wherein the water transpiration property of the preparation is 10 mg/day/cm^2 or more. 2. The preparation for patching according to claim 1, wherein the backing layer is a polyester film having a thickness of 0.5 to 4.9 μm. 3. The patch preparation according to claim 1, wherein the thin film layer is a polyester film having a thickness of 2 μm or less. 4. The preparation for patching according to claim 1, wherein the adhesive layer containing the drug comprises an acrylic adhesive. 5. The polyester film according to claim 2 or 3, wherein the amount of solid fine particles present in the film layer is 0.
．． 01 to 1% by weight, and the average particle size is 0.01 to 1% by weight.
A patch that is a polyester film having a particle diameter of 1 μm and an average particle diameter substantially not exceeding 1.5 times the thickness of the polyester film. 6. The adhesive patch according to any one of claims 1 to 5, wherein the adhesive is an adhesive made of an acrylic resin. 7. The drug is isosorbide nitrate, nitroglycerin, buprenorphine, estradiol, progesterone,
The patch according to any one of claims 1 to 6, which is one or more drugs selected from ketotifen, vinpocetine, nicotine, and derivatives thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18709390A JPH0477419A (en) | 1990-07-17 | 1990-07-17 | Formulation for patching |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP18709390A JPH0477419A (en) | 1990-07-17 | 1990-07-17 | Formulation for patching |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0477419A true JPH0477419A (en) | 1992-03-11 |
Family
ID=16199985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP18709390A Pending JPH0477419A (en) | 1990-07-17 | 1990-07-17 | Formulation for patching |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0477419A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5603947A (en) * | 1993-07-09 | 1997-02-18 | Cygnus Terapeutic Systems | Method and device for providing nicotine replacement therapy transdermally/transbuccally |
| KR20020035398A (en) * | 2000-11-06 | 2002-05-11 | 김윤 | Transdermal drug delivery system using diclofenac diethyl ammonium |
| US7232261B1 (en) | 1999-04-23 | 2007-06-19 | Fujikura Ltd. | Optical ferrule and molding method therefor, and optical connector using this optical ferrule |
| JP2008520733A (en) * | 2004-11-22 | 2008-06-19 | イズン ファーマシューティカルズ コーポレーション | Transmucosal delivery device |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6277314A (en) * | 1985-09-30 | 1987-04-09 | Nitto Electric Ind Co Ltd | Medicinal pharmaceutical |
| JPS63270621A (en) * | 1987-04-28 | 1988-11-08 | Nitto Electric Ind Co Ltd | Moisture-permeable variable type application pharmaceutical |
-
1990
- 1990-07-17 JP JP18709390A patent/JPH0477419A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6277314A (en) * | 1985-09-30 | 1987-04-09 | Nitto Electric Ind Co Ltd | Medicinal pharmaceutical |
| JPS63270621A (en) * | 1987-04-28 | 1988-11-08 | Nitto Electric Ind Co Ltd | Moisture-permeable variable type application pharmaceutical |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5603947A (en) * | 1993-07-09 | 1997-02-18 | Cygnus Terapeutic Systems | Method and device for providing nicotine replacement therapy transdermally/transbuccally |
| US7232261B1 (en) | 1999-04-23 | 2007-06-19 | Fujikura Ltd. | Optical ferrule and molding method therefor, and optical connector using this optical ferrule |
| KR20020035398A (en) * | 2000-11-06 | 2002-05-11 | 김윤 | Transdermal drug delivery system using diclofenac diethyl ammonium |
| JP2008520733A (en) * | 2004-11-22 | 2008-06-19 | イズン ファーマシューティカルズ コーポレーション | Transmucosal delivery device |
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