JPS6393714A - Plaster for transcutaneous absorption - Google Patents
Plaster for transcutaneous absorptionInfo
- Publication number
- JPS6393714A JPS6393714A JP24067986A JP24067986A JPS6393714A JP S6393714 A JPS6393714 A JP S6393714A JP 24067986 A JP24067986 A JP 24067986A JP 24067986 A JP24067986 A JP 24067986A JP S6393714 A JPS6393714 A JP S6393714A
- Authority
- JP
- Japan
- Prior art keywords
- drug
- adhesive layer
- patch
- adhesive
- weight
- 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
- 238000010521 absorption reaction Methods 0.000 title claims description 14
- 239000011505 plaster Substances 0.000 title abstract 3
- 229940079593 drug Drugs 0.000 claims abstract description 94
- 239000003814 drug Substances 0.000 claims abstract description 94
- 239000007787 solid Substances 0.000 claims abstract description 5
- 239000012790 adhesive layer Substances 0.000 claims description 45
- 239000000853 adhesive Substances 0.000 claims description 29
- 230000001070 adhesive effect Effects 0.000 claims description 29
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 239000008280 blood Substances 0.000 abstract description 23
- 210000004369 blood Anatomy 0.000 abstract description 23
- 239000013078 crystal Substances 0.000 abstract description 14
- 238000010438 heat treatment Methods 0.000 abstract description 8
- 239000010410 layer Substances 0.000 abstract description 5
- 239000004820 Pressure-sensitive adhesive Substances 0.000 abstract 4
- 239000000758 substrate Substances 0.000 abstract 2
- 230000007774 longterm Effects 0.000 abstract 1
- 230000035699 permeability Effects 0.000 abstract 1
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- -1 polyethylene Polymers 0.000 description 16
- 229960000905 indomethacin Drugs 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000003623 enhancer Substances 0.000 description 6
- 229920001577 copolymer Polymers 0.000 description 5
- 229960000201 isosorbide dinitrate Drugs 0.000 description 5
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229920001971 elastomer Polymers 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000005060 rubber Substances 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 244000043261 Hevea brasiliensis Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 239000010419 fine particle Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
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- 229920005989 resin Polymers 0.000 description 3
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- 150000003505 terpenes Chemical class 0.000 description 3
- 235000007586 terpenes Nutrition 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
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- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960004022 clotrimazole Drugs 0.000 description 2
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 229960004930 fludiazepam Drugs 0.000 description 2
- ROYOYTLGDLIGBX-UHFFFAOYSA-N fludiazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F ROYOYTLGDLIGBX-UHFFFAOYSA-N 0.000 description 2
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 2
- 230000007721 medicinal effect Effects 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- KJONHKAYOJNZEC-UHFFFAOYSA-N nitrazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1 KJONHKAYOJNZEC-UHFFFAOYSA-N 0.000 description 2
- 229960001454 nitrazepam Drugs 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920001195 polyisoprene Polymers 0.000 description 2
- 229920002635 polyurethane Polymers 0.000 description 2
- 239000004814 polyurethane Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- BFUXUGOZJVHVMR-UHFFFAOYSA-N 1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide Chemical compound N1CNS(=O)(=O)C2=CC(S(=O)(=O)N)=CC=C21 BFUXUGOZJVHVMR-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
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- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- ROGIWVXWXZRRMZ-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1 ROGIWVXWXZRRMZ-UHFFFAOYSA-N 0.000 description 1
- MEAPRSDUXBHXGD-UHFFFAOYSA-N 3-chloro-n-(4-propan-2-ylphenyl)propanamide Chemical compound CC(C)C1=CC=C(NC(=O)CCCl)C=C1 MEAPRSDUXBHXGD-UHFFFAOYSA-N 0.000 description 1
- CPHGOBGXZQKCKI-UHFFFAOYSA-N 4,5-diphenyl-1h-imidazole Chemical compound N1C=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 CPHGOBGXZQKCKI-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
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- 229920002799 BoPET Polymers 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- ZNIFSRGNXRYGHF-UHFFFAOYSA-N Clonidine hydrochloride Chemical compound Cl.ClC1=CC=CC(Cl)=C1NC1=NCCN1 ZNIFSRGNXRYGHF-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
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- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 1
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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、薬物の経皮吸収性に優れた経皮吸収貼付剤に
関する。DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a transdermal patch with excellent transdermal drug absorption.
（従来の技術）
全身もしくは局部での薬効を得るために、経皮吸収貼付
剤を用い、薬物（生理活性物質）を皮膚を介して吸収さ
せることが行われている。経皮吸収貼付剤は、柔軟な支
持体と、薬物を含有する粘着剤層とを有する。粘着剤層
は、天然ゴム、合成ゴム、アクリル系樹脂などの重合体
から構成されている。(Prior Art) In order to obtain systemic or local medicinal effects, drugs (physiologically active substances) are absorbed through the skin using transdermal patches. Transdermal patches have a flexible support and an adhesive layer containing a drug. The adhesive layer is made of a polymer such as natural rubber, synthetic rubber, or acrylic resin.
粘着剤層に含有される薬物量は９通常９重合体の飽和溶
解度以下とされている。しかし、飽和溶解度以下の薬物
量では５人体に吸収される薬物量が少ないため、充分な
薬効が得られない。薬物吸収量を増すために、粘着剤層
の層厚を厚くしたり貼付剤の寸法を大きくすれば、高価
となるうえに使用者に違和感を与える。The amount of drug contained in the adhesive layer is usually below the saturation solubility of the 9 polymer. However, if the amount of drug is below the saturation solubility, the amount of drug absorbed by the human body is small, and therefore sufficient medicinal efficacy cannot be obtained. Increasing the thickness of the adhesive layer or increasing the size of the patch in order to increase the amount of drug absorption increases the cost and gives the user a sense of discomfort.
このような欠点を解決するために１例えば、特開昭６０
−１８５７１３号公報には２重合体（粘着基剤）の飽和
溶解度以上の薬物を粘着剤層に含有させた経皮吸収貼付
剤が提案されている。この貼付剤においては、飽和溶解
度を越える薬物は、はぼ均一の再結晶微粒子状態で分散
されている。このような貼付剤を皮膚表面に貼付すると
、粘着剤中の薬物は経皮吸収され、それに伴って非溶解
状Ｂ（分散状態）の薬物が、順次粘着剤中に補充される
。In order to solve these drawbacks, for example,
Japanese Patent Publication No. 185713 proposes a transdermal patch in which the adhesive layer contains a drug at a level higher than the saturation solubility of the bipolymer (adhesive base). In this patch, the drug exceeding the saturation solubility is dispersed in the form of almost uniform recrystallized fine particles. When such a patch is applied to the skin surface, the drug in the adhesive is absorbed transdermally, and the drug in an undissolved state B (dispersed state) is sequentially replenished into the adhesive.
このように、貼付剤の貼付後の粘着剤中の薬物濃度は、
飽和溶解度に保たれるか、もしくは薬物放出速度と薬物
再溶解速度とのバランスで決まる所定のく飽和溶解度以
下の） ｔＭ度に保たれる。従って、この貼付剤は、薬
物の単位面積あたりの含有量を高くする効果があるが、
それは単に粘着剤層の厚みを増したのと同等の効果であ
り２例えば。In this way, the drug concentration in the adhesive after application of the patch is
The solubility is maintained at a saturation solubility, or at a predetermined tM (below the saturation solubility) determined by the balance between drug release rate and drug redissolution rate. Therefore, this patch has the effect of increasing the drug content per unit area, but
This is the same effect as simply increasing the thickness of the adhesive layer, for example.
薬物の血中濃度や薬物の初期吸収性の改善はほとんど認
められず、薬物の皮膚透過量の改善も顕著ではない。さ
らに、過剰の薬物が巨大な再結晶微粒子となって表面に
偏在し、そのため粘着性が低下することもある。Almost no improvement was observed in the blood concentration of the drug or the initial absorption of the drug, and there was also no significant improvement in the amount of drug permeated through the skin. Furthermore, excess drug becomes large recrystallized fine particles that are unevenly distributed on the surface, which may reduce adhesiveness.
特公昭６０−５９２０７号公報には、接触した薬物が移
行しうる重合物性フィルムを支持体として用いた複合製
剤（貼付剤）の製法が開示されている。この貼付剤は、
上記フィルム（もしくはシート）表面に、経皮吸収性薬
物（少なくとも０℃で固体である）を粘着基剤に該薬物
の飽和溶解度以上の割合で添加した粘着剤の層を形成し
てなる。このような貼付剤では、粘着剤層の飽和溶解度
を越える量の薬物は、支持体中に移行する。貼付剤を皮
膚表面に貼付すると、粘着剤中の薬物の経皮吸収に伴い
支持体中の薬物が順次粘着剤中に移行して補充されるた
め、Ｎ物吸収量が増す。このような貼付剤では、薬物が
結晶化して粘着剤の粘着性が低下したり、結晶化薬物の
再溶解速度が遅いことに起因する薬物放出速度の低下が
起こらない。しかし、支持体の薬物飽和溶解度を越える
過剰の薬物を粘着基剤中に含有させることはできないた
め。Japanese Patent Publication No. 60-59207 discloses a method for producing a composite preparation (patch) using a polymeric physical film as a support to which a drug on contact can migrate. This patch is
A layer of an adhesive is formed on the surface of the film (or sheet), in which a transdermally absorbable drug (which is solid at at least 0° C.) is added to an adhesive base in a proportion equal to or higher than the saturation solubility of the drug. In such patches, an amount of drug that exceeds the saturated solubility of the adhesive layer migrates into the support. When the patch is applied to the skin surface, the drug in the support is sequentially transferred into the adhesive and replenished as the drug in the adhesive is absorbed transdermally, increasing the amount of N-substance absorbed. In such a patch, the drug does not crystallize and the tackiness of the adhesive decreases, and the drug release rate does not decrease due to the slow redissolution rate of the crystallized drug. However, it is not possible to contain an excess of drug in the adhesive base that exceeds the saturation solubility of the drug in the support.
支持体の薬物溶解能や厚みにより薬物含有量が制限され
る。この貼付剤の支持体からは、放出された薬物を補う
量の薬物が分配に従って供給されるが、粘着剤層の薬物
濃度は飽和溶解度以下に保たれる。それゆえ、この貼付
剤も上記薬物微粒子を粘着剤層中に含有する貼付剤と同
様、薬物の血中濃度、薬物の初期吸収性の改善はほとん
ど認められず、薬物の皮膚透過量の改善も顕著ではない
。The drug content is limited by the drug dissolving ability and thickness of the support. An amount of drug that compensates for the released drug is supplied from the support of this patch according to the distribution, but the drug concentration in the adhesive layer is kept below the saturation solubility. Therefore, similar to the above-mentioned patch containing drug fine particles in the adhesive layer, this patch shows almost no improvement in the blood concentration of the drug or the initial absorption of the drug, and there is no improvement in the amount of drug permeated through the skin. Not noticeable.
（発明が解決しようとする問題点）
本発明は上記従来の問題点を解決するものであり、その
目的とするところは、単位面積あたりの薬物含量が高く
、かつその薬物量に比例して薬物の皮膚透過性の高い経
皮吸収貼付剤を提供することにある。本発明の他の目的
は、上記特徴に加えさらに薬物の初期放出性が高く、か
つ高レベルの血中濃度を維持しうる。経皮吸収貼付剤を
提供することにある。(Problems to be Solved by the Invention) The present invention is intended to solve the above-mentioned conventional problems, and its purpose is to achieve a high drug content per unit area, and to increase the drug content in proportion to the drug amount. The object of the present invention is to provide a transdermal patch with high skin permeability. Another object of the present invention is that, in addition to the above-mentioned characteristics, the initial release of the drug is high and a high level of blood concentration can be maintained. The purpose of the present invention is to provide a transdermal patch.
（問題点を解決するための手段および作用）本発明の経
皮吸収貼付剤は、薬物不透過性支持体表面に、少なくと
も３０℃で固体の薬物を含有する粘着剤層が形成された
経皮吸収貼付剤であって。(Means and effects for solving the problems) The transdermal patch of the present invention is a transdermal patch in which an adhesive layer containing a drug that is solid at at least 30° C. is formed on the surface of a drug-impermeable support. It is an absorbent patch.
該粘着剤が該薬物を飽和溶解度以上の割合で含有し、該
貼付剤があらかじめ加熱され、該薬物が該粘着剤層中に
過飽和溶解状態で存在し、そのことにより上記目的が達
成される。The adhesive contains the drug in a proportion equal to or higher than the saturation solubility, the patch is heated in advance, and the drug exists in the adhesive layer in a supersaturated dissolved state, thereby achieving the above object.
本発明の経皮吸収貼付剤の粘着剤層に用いられる粘着基
剤としては２通常の貼付剤の粘着剤層に用いられる重合
体が用いられる。それには例えば。As the adhesive base used in the adhesive layer of the transdermal patch of the present invention, there are used polymers that are commonly used in the adhesive layer of ordinary patches. For example.
ポリビニルアルキルエーテル、ポリ （メタ）アクリレ
ート、アクリル酸２エチルヘキシル−メタクリル酸２エ
チルヘキシル共重合体、アクリル酸２エチルへキシル−
ビニルピロリドン共重合体、ポリウレタン、スチレン−
イソプレン−スチレンブロック共重合体、ポリイソブチ
レンゴム、ポリイソプレンゴム、ブチルゴム、天然ゴム
、シリコーン樹脂、テルペン樹脂がある。これら重合体
には。Polyvinyl alkyl ether, poly(meth)acrylate, 2-ethylhexyl acrylate-2-ethylhexyl methacrylate copolymer, 2-ethylhexyl acrylate
Vinylpyrrolidone copolymer, polyurethane, styrene
Examples include isoprene-styrene block copolymer, polyisobutylene rubber, polyisoprene rubber, butyl rubber, natural rubber, silicone resin, and terpene resin. For these polymers.
怒圧接着性を付与するために、公知の粘着性付与剤、軟
化剤、充填剤、老化防止剤などが添加されてもよい。In order to impart anger pressure adhesion, known tackifiers, softeners, fillers, anti-aging agents, etc. may be added.
貼付剤の支持体は、経皮吸収貼付剤に自己支持性を付与
するとともに粘着剤層中の薬物の揮散や移行を防止する
ために設けられ、薬剤不透過性の素材が用いられる。そ
れには９例えば、ポリエチレン、ポリプロピレン、ポリ
アクリル酸エステル。The support for the patch is provided to provide self-supporting properties to the transdermal patch and to prevent volatilization or migration of the drug in the adhesive layer, and is made of a drug-impermeable material. For example, polyethylene, polypropylene, polyacrylic acid ester.
ポリウレタン、ポリエステル、ポリビニルアルコール、
ポリ塩化ビニル、ポリ塩化ビニリデン、ポリアミド、エ
チレン性共重合体ゴム、からなるフィルムまたはシート
；これらの積層体；上記素材を用いた多孔性フィルムま
たはシート；不織布。polyurethane, polyester, polyvinyl alcohol,
Films or sheets made of polyvinyl chloride, polyvinylidene chloride, polyamide, or ethylenic copolymer rubber; laminates thereof; porous films or sheets using the above materials; nonwoven fabrics.
織布２紙などの繊維性フィルムまたはシート；金属箔；
表面に金属蒸着を施した金属箔のフィルムまたはシート
がある。これらのうち、皮膚面に対して追従性を有する
支持体が好適に用いられる。Woven fabric 2 Fibrous film or sheet such as paper; Metal foil;
There is a film or sheet of metal foil that has a metal vapor deposited surface. Among these, a support that has conformability to the skin surface is preferably used.
支持体の厚みは、５００μｍ以下、好ましくは５〜１５
０μ鶴とされる。The thickness of the support is 500 μm or less, preferably 5 to 15 μm.
It is considered to be 0μ crane.
本発明の経皮吸収性製剤に含有される薬物は。The drug contained in the transdermal absorbable preparation of the present invention.
経皮的に吸収されて薬効を発揮する薬物であり。It is a drug that is absorbed transdermally and exerts its medicinal effects.
例えば、ハイドロコーチシン、プレドニゾロン。For example, hydrocortiscin, prednisolone.
ベクロメタゾンプ口ピオナート、フルメタシン。Beclomethasone oral pionate, flumethacin.
ベータメタシン、トリアムシノロン、トリアムシノロン
アセトニド、フルオシノロン、フルオシノロンアセトニ
ド、フルオシノロンアセトニドアセテート プロピオン
酸クロベタゾールなどのコルチコステロイド類；アセト
アミノフェン、メフェナム酸、フルフェナム酸、インド
メタシン、ジクロフェナック、ジクロフェナックナトリ
ウム、アルクロフェナック、オキシフェンブタシン、フ
ェニルブタシン、イブプロフェン、フルルブブロフェン
、サリチル酸、サリチル酸メチル、ｌ−メントール、カ
ンファー、スリンダック、トルメチンナトリウム、ナプ
ロキセン、フェンブフェンなどの鎮痛消炎剤；フエノバ
ルビタール、アモハルビタール、シクロバルビタール、
トルアゾラム、ニトラゼパム、ロラゼバム、ハロペリド
ールなどの催眠鎮静剤；フルフェナジン、チオラダジン
。ジアゼパム、フルジアゼパム、フルジアゼパム。Corticosteroids such as betamethacin, triamcinolone, triamcinolone acetonide, fluocinolone, fluocinolone acetonide, fluocinolone acetonide acetate, clobetasol propionate; acetaminophen, mefenamic acid, flufenamic acid, indomethacin, diclofenac, diclofenac sodium, Analgesic anti-inflammatory agents such as clofenac, oxyphenbutacin, phenylbutacin, ibuprofen, flurbubrofen, salicylic acid, methyl salicylate, l-menthol, camphor, sulindac, tolmetin sodium, naproxen, fenbufen; phenobarbital, amoharbital , cyclobarbital,
Hypnotic sedatives such as toluazolam, nitrazepam, lorazebam, haloperidol; fluphenazine, thioradazine. Diazepam, fludiazepam, fludiazepam.
クロルプロマジンなどの精神安定剤；クロニジン。Tranquilizers such as chlorpromazine; clonidine.
塩酸クロニジン、ピンドロール、プロプラノロール、塩
酸プロプラノロール、ブフラノール、インデノロール、
ニバジビン、ロフエジキシン、ニブラジロール、ブタモ
ロール、ニフェジピンなどの抗高血圧剤；ハイドロサイ
アザイド、ベンドロフルメサイアザイド、シクロベンチ
アザイドなどの降圧利尿剤；ペニシリン、テトラサイク
リン、オキシテトラサイクリン、硫酸フラジオマイシン
。Clonidine hydrochloride, pindolol, propranolol, propranolol hydrochloride, bufranol, indenolol,
Antihypertensive agents such as nivazibine, lofedixin, nibradirol, butamorrol, nifedipine; antihypertensive diuretics such as hydrothiazide, bendroflumeshiazide, cyclobenziazide; penicillin, tetracycline, oxytetracycline, fradiomycin sulfate.
エリスロマイシン、クロラムフェニコールなどの抗生物
質；リドカイン、ペンシカイン、アミノ安息香酸エチル
などの麻酔剤；塩化ベンザルコニウム、ニトロフラゾン
、ナイスクチン、アセトスルファミン、クロトリマゾー
ルなどの抗菌性物質；ペンタマイシン、アムホテリシン
Ｂ、ビロールニドリン、クロトリマゾールなどの抗真菌
物質；ビタミンＡ、エルゴカルシフェロール、コレカル
シフェロール、オクトチアミン、リボフラビン酪酸エス
テルなどのビタミン剤；ニトラゼパム、メプロパメート
、クロナゼパムなどの抗てんかん剤；イソソルビドジナ
イトレート、エリスリドーステトラナイトレイト、ペン
タエリドーステトラナイトレイト、プロパチルナイトレ
ートなどの冠血管拡張剤；塩酸ジフェンヒドラミン、ク
ロルフェニラミン、ジフェニルイミダゾールなどの抗ヒ
スタミン剤；デキストロメトルファン、テルブタリン。Antibiotics such as erythromycin, chloramphenicol; anesthetics such as lidocaine, pensicaine, ethyl aminobenzoate; antibacterial substances such as benzalkonium chloride, nitrofurazone, nyscutin, acetosulfamine, clotrimazole; pentamycin, amphotericin B , virolnidrine, clotrimazole; vitamins such as vitamin A, ergocalciferol, cholecalciferol, octothiamine, riboflavin butyrate; antiepileptic agents such as nitrazepam, mepropamate, clonazepam; isosorbide dinitrate, Coronary vasodilators such as erythridose-stetranitrate, pentaerydose-stetranitrate, propatyl nitrate; antihistamines such as diphenhydramine hydrochloride, chlorpheniramine, diphenylimidazole; dextromethorphan, terbutaline.
エフェドリン、塩酸エフェドリン、サルブタモール、イ
ソプロテノールなどの鎮咳剤；ボロゲステロン、エスト
ラジオールなどの性ホルモン；ドキセピンなどの抗ｒ剤
；５−フルオロウラシル、ジヒドロエルゴタミン、フェ
ンタニール、デスモジレシン。ジゴキシン、メトクロプ
ラミド、ドンベリド、スコポラミン、臭化水素酸スコポ
ラミン。Antitussives such as ephedrine, ephedrine hydrochloride, salbutamol, isoprotenol; sex hormones such as borogesterone, estradiol; anti-retroactive agents such as doxepin; 5-fluorouracil, dihydroergotamine, fentanyl, desmodilesin. digoxin, metoclopramide, donbelide, scopolamine, scopolamine hydrobromide.
プロスタグランディンなどの他の薬物がある。There are other drugs such as prostaglandins.
本発明の経皮吸収貼付剤の粘着剤層には、薬物の経皮吸
収を促進するために、必要に応じて吸収促進剤が添加さ
れる。吸収促進剤には１例えば。If necessary, an absorption enhancer is added to the adhesive layer of the transdermal patch of the present invention in order to promote transdermal absorption of the drug. Examples of absorption enhancers include:
ジエチレングリコール、プロピレングリコール。Diethylene glycol, propylene glycol.
ポリエチレングリコールなどのグリコール頚；オリーブ
油、スクアレン、ラノリンなどの油脂類；尿素、アラン
トインなどの尿素誘導体；ミリスチン酸イソプロピル、
バルミチン酸イソプロピル。Glycol necks such as polyethylene glycol; fats and oils such as olive oil, squalene, and lanolin; urea derivatives such as urea and allantoin; isopropyl myristate,
Isopropyl valmitate.
セバシン酸ジエチルなどの高級脂肪酸エステル。Higher fatty acid esters such as diethyl sebacate.
高級脂肪酸トリグリセリド；脂肪酸（モノ）ジェタノー
ルアミド；サリチル酸；サリチル酸エステルなどがある
。吸収促進剤は、一種または二種以上混合して用いられ
、粘着剤層中に３０重量％以下の範囲で含有される。These include higher fatty acid triglycerides; fatty acid (mono)jetanolamide; salicylic acid; and salicylic acid esters. The absorption enhancer may be used alone or in combination of two or more, and is contained in the adhesive layer in an amount of 30% by weight or less.
本発明の経皮吸収貼付剤は、上記粘着基剤、支持体、薬
物および必要に応じて吸収促進剤などを用いて通常の貼
付剤に準じて調製される。例えば。The transdermal patch of the present invention is prepared in the same manner as a conventional patch using the above-mentioned adhesive base, support, drug and, if necessary, an absorption enhancer. for example.
粘着基剤となるポリマーの有機溶剤溶液に薬物および必
要に応じて吸収促進剤などを加えて、これを支持体表面
の塗布し乾燥させる。剥離紙上に粘着剤層を形成し、こ
れを支持体と密着させてもよい。このような貼付剤調製
時には、薬物は、使用する粘着基剤（必要に応じて粘着
性付与剤や吸収促進剤を含む）の該薬物の飽和溶解度の
１．２倍以上、好ましくは１．５〜３．０倍の割合で粘
着剤中に配合する。粘着剤中に混合された薬物は過飽和
溶解状態で存在する。A drug and, if necessary, an absorption enhancer are added to an organic solvent solution of a polymer serving as an adhesive base, and this is applied to the surface of a support and dried. An adhesive layer may be formed on a release paper and brought into close contact with the support. When preparing such a patch, the drug has a saturated solubility of at least 1.2 times, preferably 1.5 times, the saturation solubility of the drug in the adhesive base used (including tackifiers and absorption enhancers as necessary). It is blended into the adhesive at a ratio of ~3.0 times. The drug mixed in the adhesive exists in a supersaturated dissolved state.
このような貼付剤を長期間保存すると、過飽和溶解状態
の薬物が微細な結晶となって粘着剤層中に徐々に析出す
るようになる。そのため９本発明においては、この貼付
剤は使用前に加熱される。When such a patch is stored for a long period of time, the supersaturated dissolved drug becomes fine crystals and gradually precipitates into the adhesive layer. Therefore, in the present invention, the patch is heated before use.
加熱により、析出した薬物も再び過飽和溶解状態となっ
て粘着剤層中に存在するようになる。加熱の温度は、含
有される薬物が粘着剤中に再溶解できる温度であればよ
い。ここで、加熱とは、直接熱を加えること以外に、電
磁波を照射して分子運動を活発化し熱を発生させる電子
レンジなどによる処理をも包含していう。By heating, the precipitated drug also returns to a supersaturated dissolved state and comes to exist in the adhesive layer. The heating temperature may be any temperature that allows the drug contained in the adhesive to be redissolved. Here, heating includes not only direct application of heat but also treatment using a microwave oven or the like that activates molecular motion by irradiating electromagnetic waves to generate heat.
このように薬物を過飽和溶解状態で含有する貼付剤は、
従来の薬物再結晶微粒子が粘着剤層に存在する貼付剤や
薬物が移行しうる支持体を備えた貼付剤に比べ、貼付剤
を皮膚表面に貼付したときの薬物濃度グラジェントが大
きい。従ってフィックの拡散方程式による薬物経皮透過
量が大きくなる。本発明の経皮吸収貼付剤は、それゆえ
高い血中濃度レベルを長時間にわたって維持でき、バイ
オアベイラビリティが高い。薬物の初期放出性も良好で
ある。このような貼付剤を用いると、より小面積であっ
ても従来と同一レベルの薬効が得られる。In this way, patches containing drugs in a supersaturated dissolved state are
Compared to conventional patches in which drug recrystallized microparticles are present in the adhesive layer or patches with a support to which the drug can migrate, the drug concentration gradient when applied to the skin surface is larger. Therefore, the amount of drug permeated through the skin increases according to Fick's diffusion equation. The transdermal patch of the present invention can therefore maintain high blood concentration levels for long periods of time and has high bioavailability. The initial drug release properties are also good. When such a patch is used, the same level of medicinal efficacy as before can be obtained even in a smaller area.
（実施例） 以下に本発明を実施例について述べる。(Example) The present invention will be described below with reference to examples.
実施例および比較例において、イソソルビドジナイトレ
ートの薬物血中濃度はガスクロマトグラフィー、そして
インドメタシンの薬物血中濃度は液体クロマトグラフィ
ーにて測定した。In the Examples and Comparative Examples, the drug blood concentration of isosorbide dinitrate was measured by gas chromatography, and the drug blood concentration of indomethacin was measured by liquid chromatography.
次２
アクリル酸２エチルへキシル−ビニルピロリドン共重合
体くアクリル酸２工チルヘキシル８７重量部に対しビニ
ルピロリドンを１３重量部の割合で含有する）の２０重
量％酢酸エチル溶液１００重量部に。Next 2 A 20% by weight solution of 2-ethylhexyl acrylate-vinylpyrrolidone copolymer (containing 13 parts by weight of vinylpyrrolidone to 87 parts by weight of 2-ethylhexyl acrylate) in ethyl acetate was added to 100 parts by weight.
イソソルビドジナイトレー） （ＩＳＤＮ） ５重量部
を添加し、ディシルバーにて均一に混合した。得られた
溶液を、厚さ４５μｍのポリエチレンテレフタレー）
（ＰＥＴ）製離型フィルム上に塗布し、乾燥して粘着剤
層を形成した。この粘着剤層にＰＥＴフィルム（厚さ１
０μＩＩ＋）支持体を積層して、経皮吸収貼付剤を得た
。粘着剤層の厚さは４０μｍであり、粘着剤層中の薬物
濃度は２０重量％であった。上記粘着基材のｌ５ＤＮ飽
和溶解度は１１．１重量％である。5 parts by weight of isosorbide dinitrate (ISDN) were added and mixed uniformly using a dissilver. The obtained solution was poured into polyethylene terephthalate (45 μm thick).
(PET) release film and dried to form an adhesive layer. This adhesive layer is covered with PET film (thickness 1
0μII+) supports were laminated to obtain a transdermal patch. The thickness of the adhesive layer was 40 μm, and the drug concentration in the adhesive layer was 20% by weight. The l5DN saturation solubility of the adhesive base material is 11.1% by weight.
このようにして得られた貼付剤を室温で３ケ月間放遺し
たところ、粘着剤層中にｌ５ＯＮの微細な結晶が析出し
た。この貼付剤をギヤーオーブン中。When the patch thus obtained was left at room temperature for 3 months, fine crystals of 15ON precipitated in the adhesive layer. Put this patch in a gear oven.
７０℃で１０分間加熱した。ｌ５ＤＮの結晶は完全に溶
解し、粘着剤中に過飽和溶解状態で存在するようになっ
た。このようにして得られた経皮吸収貼付剤１０ｃＩ１
１を、脱毛処理した日本内色種家兎の背部に貼付し、薬
物血中濃度の経時変化を測定した。これらの結果を表１
に示す。実施例２および比較例１〜３の結果もあわせて
表１に示す。Heated at 70°C for 10 minutes. The l5DN crystals were completely dissolved and existed in the adhesive in a supersaturated dissolved state. Transdermal absorption patch 10cI1 thus obtained
1 was applied to the back of a Japanese domestic rabbit that had undergone hair removal treatment, and the change in blood drug concentration over time was measured. These results are shown in Table 1.
Shown below. The results of Example 2 and Comparative Examples 1 to 3 are also shown in Table 1.
止較糎よ
ｌ５ＤＮ結晶の析出した貼付剤を加熱せずにそのまま家
兎背部に貼付して血中濃度を測定したこと以外は実施例
１と同様である。The procedure was the same as in Example 1, except that the patch containing the precipitated 15DN crystals was directly applied to the back of a rabbit without heating, and the blood concentration was measured.
北較斑主
ｌ５ＤＮ添加量を２．５重量部とすること以外は、実施
例１と同様の方法で経皮吸収貼付剤の調製を行なった。A transdermal patch was prepared in the same manner as in Example 1, except that 2.5 parts by weight of Hokkai Makushi 15DN was added.
但し、粘着剤層の厚さは８０μｍである。However, the thickness of the adhesive layer is 80 μm.
粘着剤層中のＩｓ ｎ Ｎ ？、Ｑ度は１１．１重量％
であり、３ケ月経過後もＩ ＳＤＮは粘着剤層中に均一
に溶解していた。Is n N in the adhesive layer? , Q degree is 11.1% by weight
Even after 3 months had passed, ISDN was uniformly dissolved in the adhesive layer.
ス１１１劃
粘着基剤溶液としてスチレン−イソプレン−スチレンブ
ロック共重合体２５重量部、ポリイソプレンゴム２５重
量部およびテルペン樹脂５０重量部の混合物の２０重景
％テトラヒドロフラン溶液を用い。As the adhesive base solution, a 20% tetrahydrofuran solution of a mixture of 25 parts by weight of styrene-isoprene-styrene block copolymer, 25 parts by weight of polyisoprene rubber and 50 parts by weight of terpene resin was used.
ｌ５ＤＮ １．０４重量部を添加したこと以外は、実施
例１と同様にして経皮吸収貼付剤を得た。但し、粘着剤
層の厚さは１００μ信である。粘着剤層中のｌ５ＤＮ濃
度は４．９４重量％であり、 ｌ５ＤＮは均一に溶解し
ていた。上記粘着基剤のｌ５ＯＮの飽和溶解度は２．８
重量％である。A transdermal patch was obtained in the same manner as in Example 1, except that 1.04 parts by weight of 15DN was added. However, the thickness of the adhesive layer is 100μ thick. The l5DN concentration in the adhesive layer was 4.94% by weight, and l5DN was uniformly dissolved. The saturation solubility of l5ON in the above adhesive base is 2.8
Weight%.
このようにして得られた貼付剤を室温で３ケ月間放置し
たところ、粘着剤層中にｌ５ＤＮの微細な結晶が析出し
た。この貼付剤をアルミ包材でシールし、沸騰水中で１
０分間加熱した。Ｉ ＳＤＨの結晶は完全に溶解し、粘
着剤中に過飽和溶解状態で存在するようになった。この
貼付剤を用い、実施例１と同様の方法でｌ５ＤＮの血中
濃度の測定を行なった。When the patch thus obtained was left at room temperature for 3 months, fine crystals of 15DN precipitated in the adhesive layer. Seal this patch with aluminum packaging material and immerse it in boiling water for 1 hour.
Heated for 0 minutes. ISDH crystals were completely dissolved and existed in the adhesive in a supersaturated dissolved state. Using this patch, the blood concentration of 15DN was measured in the same manner as in Example 1.
土較炭主
ｌ５ＤＮ結晶の析出した貼付剤を加熱せずにそのまま家
兎背部に貼付して血中濃度を測定したこと以外は実施例
２と同様である。The procedure was the same as in Example 2, except that the patch containing the precipitated 15DN crystals was directly applied to the back of a rabbit without heating, and the blood concentration was measured.
尖施貫主
アクリル酸２エチルへキシル−ビニルピロリドン共重合
体（アクリル酸２工チルヘキシル９７重量部に対し、ビ
ニルピロリドンを３重量部の割合で含有する）の２０重
量％酢酸エチル溶液に、薬物としてインドメタシン２重
量部を添加し、実施例１に準じて経皮吸収貼付剤を得た
。粘着剤層の厚さは５０μｍであり、粘着剤層中の薬物
濃度は９．０９重量％であった。上記粘着基剤のインド
メタシン飽和溶解度は４．８重量％である。A 20% by weight solution of 2-ethylhexyl acrylate-vinylpyrrolidone copolymer (containing 3 parts by weight of vinylpyrrolidone to 97 parts by weight of 2-ethylhexyl acrylate) in ethyl acetate was added as a drug. A transdermal patch was obtained according to Example 1 by adding 2 parts by weight of indomethacin. The thickness of the adhesive layer was 50 μm, and the drug concentration in the adhesive layer was 9.09% by weight. The saturation solubility of indomethacin in the adhesive base is 4.8% by weight.
このようにして得られた貼付剤を室温で３ケ月間放置し
たところ、粘着剤層中にインドメタシンの微細な結晶が
析出した。この貼付剤を電子レンジ（９４０Ｗ）で５分
間加熱した。インドメタシンの結晶は完全に溶解し、粘
着剤中に過飽和溶解状態で存在するようになった。この
貼付剤を用い、実施例１と同様の方法でインドメタシン
の血中濃度の測定を行なった。その結果を表２に示す。When the patch thus obtained was left at room temperature for 3 months, fine crystals of indomethacin precipitated in the adhesive layer. This patch was heated in a microwave oven (940W) for 5 minutes. The indomethacin crystals were completely dissolved and existed in the adhesive in a supersaturated dissolved state. Using this patch, the blood concentration of indomethacin was measured in the same manner as in Example 1. The results are shown in Table 2.
実施例４および比較例４〜６の結果もあわせて表２に示
す。The results of Example 4 and Comparative Examples 4 to 6 are also shown in Table 2.
此笠±エ
インドメタシン結晶の析出した貼付剤を加熱せずにその
まま家兎背部に貼付して血中濃度を測定したこと以外は
実施例３と同様である。The procedure was the same as in Example 3, except that the patch containing precipitated crystals of domethacin was directly applied to the back of a rabbit without heating, and the blood concentration was measured.
工較１
インドメタシン添加量を１重量部にすること以外は、実
施例３と同様の方法で経皮吸収貼付剤を調製し２血中濃
度の測定を行なった。但し、粘着剤層の厚さは９５μ情
であり、粘着剤層中の薬物濃度は、 ４．７６重重憬で
あり、３ケ月経過後も薬物は粘着剤層中に均一に溶解し
ていた。Technical Comparison 1 A transdermal patch was prepared in the same manner as in Example 3, except that the amount of indomethacin added was 1 part by weight, and the blood concentration was measured. However, the thickness of the adhesive layer was 95 μm, the drug concentration in the adhesive layer was 4.76 μm, and the drug was uniformly dissolved in the adhesive layer even after 3 months had passed.
実施■↓
粘着基剤溶液として天然ゴム５５重量部およびテルペン
樹脂４５重量部の混合物の１５重量％テトラヒドロフラ
ン溶液を用い、薬物としてインドメタシン０．７重量部
を添加したこと以外は、実施例１と同様にして経皮吸収
貼付剤を得、血中濃度の測定を行なった。但し、粘着剤
層の厚みは１００μｍである。粘着剤層中にインドメタ
シンは均一に溶解しており、その濃度は４．４６重量％
であった。本実施例の粘着基剤のインドメタシン飽和溶
解度は２．３重量％である。Implementation ■↓ Same as Example 1 except that a 15% by weight tetrahydrofuran solution of a mixture of 55 parts by weight of natural rubber and 45 parts by weight of terpene resin was used as the adhesive base solution, and 0.7 parts by weight of indomethacin was added as the drug. A transdermal patch was obtained, and the blood concentration was measured. However, the thickness of the adhesive layer is 100 μm. Indomethacin is uniformly dissolved in the adhesive layer, and its concentration is 4.46% by weight.
Met. The saturated solubility of indomethacin in the adhesive base of this example is 2.3% by weight.
このようにして得られた貼付剤を室温で３ケ月間放置し
たところ、粘着剤層中にインドメタシンの６ｈ ｌｔ［
Ｉな結晶が析出した。この貼付剤を電子レンジ（９４０
Ｗ）で５分間加熱した。インドメタシンの結晶は完全に
溶解し、粘着剤中に過飽和溶解状態で存在するようにな
った。この貼付剤を用い、実施例１と同様の方法でイン
ドメタシンの血中濃度の測定を行なった。When the patch thus obtained was left at room temperature for 3 months, 6h lt[ of indomethacin] was found in the adhesive layer.
I crystals precipitated. Microwave this patch (940
W) for 5 minutes. The indomethacin crystals were completely dissolved and existed in the adhesive in a supersaturated dissolved state. Using this patch, the blood concentration of indomethacin was measured in the same manner as in Example 1.
ル較桝亙
インドメタシン結晶の析出した貼付剤を加熱せずにその
まま家兎背部に貼付して血中濃度を測定したこと以外は
実施例４と同様である。The procedure was the same as in Example 4, except that the patch containing the precipitated indomethacin crystals was directly applied to the back of a rabbit without heating, and the blood concentration was measured.
（以下余白）
表１および表２から、薬物が粘着剤層中に過飽和溶解状
態で存在する本発明の貼付剤を用いると薬物の血中濃度
が長時間にわたり高レベルに維持されることが明らかで
ある。薬物の初期血中濃度も高レベルであることがわか
る。(Left below) From Tables 1 and 2, it is clear that when using the patch of the present invention in which the drug exists in the adhesive layer in a supersaturated dissolved state, the blood concentration of the drug can be maintained at a high level for a long time. It is. It can be seen that the initial blood concentration of the drug is also at a high level.
（発明の効果）
本発明によれば、このように、薬物が粘着剤層に過飽和
溶解状態で存在する経皮吸収貼付剤が得られる。この経
皮吸収貼付剤は、薬物放出性に優れている。薬物放出の
持続性も得られる。その結果、この経皮吸収貼付剤を皮
膚に貼付すれば、高レベルの薬物血中濃度が得られる。(Effects of the Invention) According to the present invention, a transdermal patch in which the drug exists in the adhesive layer in a supersaturated dissolved state can be obtained. This transdermal patch has excellent drug release properties. Sustained drug release is also obtained. As a result, when this transdermal patch is applied to the skin, a high level of drug concentration in the blood can be obtained.
薬物の初期血中濃度も高く、血中濃度の持続性にも優れ
る。The initial blood concentration of the drug is high, and the blood concentration is also excellent in sustainability.
以上that's all
Claims (1)
体の薬物を含有する粘着剤層が形成された経皮吸収貼付
剤であって、 該粘着剤が該薬物を飽和溶解度以上の割合で含有し、 該貼付剤があらかじめ加熱され、該薬物が該粘着剤層中
に過飽和溶解状態で存在する、 経皮吸収貼付剤。 ２、前記粘着剤が前記薬物を飽和溶解度の１．２倍以上
の割合で含有する特許請求の範囲第１項に記載の経皮吸
収貼付剤。[Scope of Claims] 1. A transdermal patch comprising an adhesive layer containing a solid drug at at least 30° C. formed on the surface of a drug-impermeable support, the adhesive layer containing a drug that is solid at at least 30°C; A transdermal absorption patch, wherein the drug is present in a supersaturated dissolved state in the adhesive layer when the patch is heated in advance. 2. The transdermal patch according to claim 1, wherein the adhesive contains the drug at a ratio of 1.2 times or more of the saturated solubility.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61240679A JPH066534B2 (en) | 1986-10-09 | 1986-10-09 | Transdermal patch |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61240679A JPH066534B2 (en) | 1986-10-09 | 1986-10-09 | Transdermal patch |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6393714A true JPS6393714A (en) | 1988-04-25 |
| JPH066534B2 JPH066534B2 (en) | 1994-01-26 |
Family
ID=17063094
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61240679A Expired - Lifetime JPH066534B2 (en) | 1986-10-09 | 1986-10-09 | Transdermal patch |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH066534B2 (en) |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03123727A (en) * | 1989-10-04 | 1991-05-27 | Nitto Denko Corp | Percutaneous absorption preparation |
| EP0572494A1 (en) * | 1991-02-18 | 1993-12-08 | Commonwealth Scientific And Industrial Research Organisation | Composition for use in transdermal administration |
| WO1998000118A3 (en) * | 1996-07-03 | 1998-03-05 | Alza Corp | Drug delivery devices and process of manufacture |
| US5906830A (en) * | 1995-09-08 | 1999-05-25 | Cygnus, Inc. | Supersaturated transdermal drug delivery systems, and methods for manufacturing the same |
| US6007837A (en) * | 1996-07-03 | 1999-12-28 | Alza Corporation | Drug delivery devices and process of manufacture |
| US6174545B1 (en) | 1997-07-01 | 2001-01-16 | Alza Corporation | Drug delivery devices and process of manufacture |
| WO2002043766A1 (en) * | 2000-11-29 | 2002-06-06 | Takeda Chemical Industries, Ltd. | Medicinal compositions and process for producing the same |
| JP2006045158A (en) * | 2004-08-06 | 2006-02-16 | Lintec Corp | Method for producing percutaneously absorbable type pharmaceutical preparation |
| JP2006513195A (en) * | 2002-12-30 | 2006-04-20 | シュバルツ ファルマ アクチェンゲゼルシャフト | Device for transdermal administration of rotigotine base |
| JP2010521525A (en) * | 2007-03-16 | 2010-06-24 | マイラン・テクノロジーズ，インコーポレイテッド | Transdermal system, production method, and stabilization of amorphous drug |
| US8441800B2 (en) | 2009-03-26 | 2013-05-14 | Panasonic Corporation | Vehicle-mounted electronic device |
| JP5270035B1 (en) * | 2012-12-06 | 2013-08-21 | 久光製薬株式会社 | Patch and method for producing the same |
| EP2749274A1 (en) | 2012-12-27 | 2014-07-02 | Hisamitsu Pharmaceutical Co., Inc. | Patch comprising oxybutynin hydrochloride and method for producing the same |
| EP2818161A1 (en) | 2013-06-28 | 2014-12-31 | Hisamitsu Pharmaceutical Co., Inc. | Method for producing supersaturated ropinirole patch |
| US9155710B2 (en) | 2011-05-31 | 2015-10-13 | Hisamitsu Pharmaceutical Co., Inc. | Ropinirole-containing patch and package thereof |
| EP2498762B1 (en) | 2009-11-12 | 2016-09-07 | LTS LOHMANN Therapie-Systeme AG | Method for preventing the crystallisation of pharmaceuticals in a polymer film |
| US9918945B2 (en) | 2011-05-31 | 2018-03-20 | Hisamitsu Pharmaceutical Co., Inc. | Ropinirole-containing patch and package thereof |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110294684A (en) | 2018-03-22 | 2019-10-01 | 日东电工株式会社 | The manufacturing method of composition containing Pregabalin and composition containing Pregabalin |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60185713A (en) * | 1984-03-05 | 1985-09-21 | Nitto Electric Ind Co Ltd | Percutaneous preparation and its production |
| JPS61148117A (en) * | 1984-12-21 | 1986-07-05 | Sekisui Chem Co Ltd | Application agent and production thereof |
-
1986
- 1986-10-09 JP JP61240679A patent/JPH066534B2/en not_active Expired - Lifetime
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60185713A (en) * | 1984-03-05 | 1985-09-21 | Nitto Electric Ind Co Ltd | Percutaneous preparation and its production |
| JPS61148117A (en) * | 1984-12-21 | 1986-07-05 | Sekisui Chem Co Ltd | Application agent and production thereof |
Cited By (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03123727A (en) * | 1989-10-04 | 1991-05-27 | Nitto Denko Corp | Percutaneous absorption preparation |
| EP0572494A1 (en) * | 1991-02-18 | 1993-12-08 | Commonwealth Scientific And Industrial Research Organisation | Composition for use in transdermal administration |
| EP0572494A4 (en) * | 1991-02-18 | 1996-05-29 | Commw Scient Ind Res Org | Composition for use in transdermal administration |
| EP0848608B1 (en) * | 1995-09-08 | 2000-12-13 | Ortho-McNeil Pharmaceutical, Inc. | Supersaturated transdermal drug delivery systems, and methods for manufacturing the same |
| US5906830A (en) * | 1995-09-08 | 1999-05-25 | Cygnus, Inc. | Supersaturated transdermal drug delivery systems, and methods for manufacturing the same |
| WO1998000118A3 (en) * | 1996-07-03 | 1998-03-05 | Alza Corp | Drug delivery devices and process of manufacture |
| US6007837A (en) * | 1996-07-03 | 1999-12-28 | Alza Corporation | Drug delivery devices and process of manufacture |
| US6174545B1 (en) | 1997-07-01 | 2001-01-16 | Alza Corporation | Drug delivery devices and process of manufacture |
| WO2002043766A1 (en) * | 2000-11-29 | 2002-06-06 | Takeda Chemical Industries, Ltd. | Medicinal compositions and process for producing the same |
| JP2006513195A (en) * | 2002-12-30 | 2006-04-20 | シュバルツ ファルマ アクチェンゲゼルシャフト | Device for transdermal administration of rotigotine base |
| JP2006045158A (en) * | 2004-08-06 | 2006-02-16 | Lintec Corp | Method for producing percutaneously absorbable type pharmaceutical preparation |
| JP2010521525A (en) * | 2007-03-16 | 2010-06-24 | マイラン・テクノロジーズ，インコーポレイテッド | Transdermal system, production method, and stabilization of amorphous drug |
| JP2014065727A (en) * | 2007-03-16 | 2014-04-17 | Mylan Technologies Inc | Amorphous drug transdermal systems, manufacturing methods, and stabilization |
| US8441800B2 (en) | 2009-03-26 | 2013-05-14 | Panasonic Corporation | Vehicle-mounted electronic device |
| EP2498762B1 (en) | 2009-11-12 | 2016-09-07 | LTS LOHMANN Therapie-Systeme AG | Method for preventing the crystallisation of pharmaceuticals in a polymer film |
| US9155710B2 (en) | 2011-05-31 | 2015-10-13 | Hisamitsu Pharmaceutical Co., Inc. | Ropinirole-containing patch and package thereof |
| US9918945B2 (en) | 2011-05-31 | 2018-03-20 | Hisamitsu Pharmaceutical Co., Inc. | Ropinirole-containing patch and package thereof |
| KR101369556B1 (en) * | 2012-12-06 | 2014-03-04 | 히사미쓰 세이야꾸 가부시키가이샤 | Patch and method for producing the same |
| JP5270035B1 (en) * | 2012-12-06 | 2013-08-21 | 久光製薬株式会社 | Patch and method for producing the same |
| EP2740472A1 (en) | 2012-12-06 | 2014-06-11 | Hisamitsu Pharmaceutical Co., Inc. | Patch and method for producing the same |
| US8802134B2 (en) | 2012-12-06 | 2014-08-12 | Hisamitsu Pharmaceutical Co., Inc. | Patch and method for producing the same |
| EP2749274A1 (en) | 2012-12-27 | 2014-07-02 | Hisamitsu Pharmaceutical Co., Inc. | Patch comprising oxybutynin hydrochloride and method for producing the same |
| US8877235B2 (en) | 2012-12-27 | 2014-11-04 | Hisamitsu Pharmaceutical Co., Inc. | Patch and method for producing the same |
| EP2818161A1 (en) | 2013-06-28 | 2014-12-31 | Hisamitsu Pharmaceutical Co., Inc. | Method for producing supersaturated ropinirole patch |
| US9320728B2 (en) | 2013-06-28 | 2016-04-26 | Hisamitsu Pharmaceutical Co., Inc. | Method for producing patch, patch and package |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH066534B2 (en) | 1994-01-26 |
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