JPS60169414A - Endermic absorption agent - Google Patents
Endermic absorption agentInfo
- Publication number
- JPS60169414A JPS60169414A JP59024421A JP2442184A JPS60169414A JP S60169414 A JPS60169414 A JP S60169414A JP 59024421 A JP59024421 A JP 59024421A JP 2442184 A JP2442184 A JP 2442184A JP S60169414 A JPS60169414 A JP S60169414A
- Authority
- JP
- Japan
- Prior art keywords
- drug
- absorption agent
- water
- composite material
- polymer compound
- 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 abstract description 20
- 229940079593 drug Drugs 0.000 claims abstract description 28
- 239000003814 drug Substances 0.000 claims abstract description 28
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 229920002379 silicone rubber Polymers 0.000 claims abstract description 4
- 229920003169 water-soluble polymer Polymers 0.000 claims description 10
- 239000002131 composite material Substances 0.000 abstract description 8
- 239000000203 mixture Substances 0.000 abstract description 8
- 239000007788 liquid Substances 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 5
- 239000002904 solvent Substances 0.000 abstract description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 abstract description 3
- 229920005573 silicon-containing polymer Polymers 0.000 abstract description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 abstract description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 abstract description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 abstract description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 abstract description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 abstract description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 abstract description 2
- 239000000661 sodium alginate Substances 0.000 abstract description 2
- 235000010413 sodium alginate Nutrition 0.000 abstract description 2
- 229940005550 sodium alginate Drugs 0.000 abstract description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 abstract description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 abstract description 2
- 229920000642 polymer Polymers 0.000 abstract 2
- 210000004877 mucosa Anatomy 0.000 abstract 1
- XZZXKVYTWCYOQX-UHFFFAOYSA-J octanoate;tin(4+) Chemical compound [Sn+4].CCCCCCCC([O-])=O.CCCCCCCC([O-])=O.CCCCCCCC([O-])=O.CCCCCCCC([O-])=O XZZXKVYTWCYOQX-UHFFFAOYSA-J 0.000 abstract 1
- 125000000914 phenoxymethylpenicillanyl group Chemical group CC1(S[C@H]2N([C@H]1C(=O)*)C([C@H]2NC(COC2=CC=CC=C2)=O)=O)C 0.000 abstract 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 abstract 1
- 230000001186 cumulative effect Effects 0.000 description 8
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 229920000260 silastic Polymers 0.000 description 6
- 230000002745 absorbent Effects 0.000 description 5
- 239000002250 absorbent Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- -1 11-dodecyl Chemical group 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229920001971 elastomer Polymers 0.000 description 4
- 239000000806 elastomer Substances 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 239000004332 silver Substances 0.000 description 4
- 229910052709 silver Inorganic materials 0.000 description 4
- 229920001296 polysiloxane Polymers 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000000084 colloidal system Substances 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000004014 plasticizer Substances 0.000 description 2
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000772991 Aira Species 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 101100008046 Caenorhabditis elegans cut-2 gene Proteins 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 241001464430 Cyanobacterium Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 230000037374 absorbed through the skin Effects 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 229940096529 carboxypolymethylene Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 201000003152 motion sickness Diseases 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 229940105132 myristate Drugs 0.000 description 1
- 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 1
- 229960001454 nitrazepam Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 239000002952 polymeric resin Substances 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- TUNFSRHWOTWDNC-UHFFFAOYSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCCC(O)=O TUNFSRHWOTWDNC-UHFFFAOYSA-N 0.000 description 1
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
【発明の詳細な説明】 本発明は経皮吸収剤に関する。[Detailed description of the invention] The present invention relates to transdermal absorption agents.
必要な部位に必要な量の薬剤を必要な時間だけ作用させ
ることによって、最小量の薬剤に最大限の効果を発揮さ
せて副作用は最小限に抑えるというドラッグ・デリバリ
−・システム（ＤｒｕｇＤｅｌｉｖｅｒｙ Ｓｙｓｔｅ
ｍ）が近来導入されてきたが、中でも薬剤の投与の実施
と中断が簡単で薬物の給配が行ない易いものとして経皮
治療システムがある。しかしながら、皮膚は生体防禦の
機能を備えた器官であるから、従来の経皮吸収剤では薬
物は皮膚バリヤーに妨げられてその極微量が経皮吸収さ
れるにすぎず、その適用はスコポラミンなどの微量でも
作用の強い薬剤か、またはニトログリセリンのようにそ
れ自身の経皮吸収性 ・が非常に高い薬剤に限られてい
た。A drug delivery system that maximizes the effect of a minimum amount of drug and minimizes side effects by applying the required amount of drug to the required area for the required time.
m) have recently been introduced, and among them, transdermal treatment systems are one that facilitates the administration and discontinuation of drug administration and facilitates drug delivery. However, since the skin is an organ with a biological defense function, with conventional transdermal absorption agents, the drug is blocked by the skin barrier and only a very small amount of it is absorbed through the skin. This was limited to drugs that had strong effects even in minute amounts, or drugs that were themselves highly absorbable through the skin, such as nitroglycerin.
このだめ、ジメチルスルフォキサイド、イソプロピルミ
ソステート、エイシン〔商品名、ネルソン・リサーチ■
製、化学名１１−ドデシルアザシクロへブタン−２−オ
ン〕などの吸収促進剤を基剤に配合して薬物の経皮吸収
を高めたシ、また基剤に水溶性高分子樹脂を配合して薬
物の放出性を高める試みがなされたが、必ずしも満足す
べき成果は得られなかった。Konodame, dimethyl sulfoxide, isopropyl misostate, Eishin [Product name, Nelson Research ■
Transdermal absorption of the drug is increased by blending an absorption enhancer such as 11-dodecyl azacyclohebutan-2-one] (manufactured by Manufacturer, Inc., chemical name: 11-dodecyl azacyclohebutan-2-one) into the base, and a water-soluble polymer resin is blended into the base. Attempts have been made to improve drug release, but satisfactory results have not always been achieved.
本発明者らは、従来の経皮吸収剤の欠点を解消すべく鋭
意研究の結果、薬物と水溶性高分子化合物の複合体を分
散したシリコーンニジストマーは薬物の放出性が高いこ
とを見出だし、本発明を完成した。As a result of intensive research aimed at resolving the drawbacks of conventional transdermal absorption agents, the present inventors discovered that a silicone nidistomer in which a complex of a drug and a water-soluble polymer compound is dispersed has high drug release properties. , completed the invention.
本発明は薬物と水溶性高分子化合物の複合体をシリコー
ンニジストマーからなる基剤に分散した経皮吸収剤であ
る。The present invention is a transdermal absorption agent in which a complex of a drug and a water-soluble polymer compound is dispersed in a base made of a silicone distomer.
ここにおいて薬物とは、クロニジン、レセルビートなど
の狭心症治療薬；コルチゾン、フルオルスロマイシン、
テトラサイクリへペニシリンなどの抗生物質；スコポラ
ミンなどの抗乗物酔薬；ジアゼパム、ニトラゼパム々ど
のマイナートランキライザーなどであり、水溶性高分子
化合物とはポリビニルピロ〃トン、ポリアクリル酸ナト
リウム、ポリビニルアルコール、アルギン酸ナトリウム
、カルボキシメチルセルロースナトリウム、カルボキシ
ポリメチレンなどである。Here, drugs include antianginal drugs such as clonidine and reservito; cortisone, fluorothromycin,
Antibiotics such as penicillin to tetracyclides; anti-motion sickness drugs such as scopolamine; minor tranquilizers such as diazepam and nitrazepam; water-soluble polymer compounds include polyvinylpyroton, sodium polyacrylate, polyvinyl alcohol, and sodium alginate. , carboxymethylcellulose sodium, carboxypolymethylene, etc.
また、シリコーンエラストマーとはポリメチルシロキサ
ン、ジメチルメチルビニルシロキサンコポリマーなどの
シリコーンポリマーからなるエラストマーであって、た
とえばダウ コーニング■製のサイラスティック３８２
〔商品名、メディカルグレードエラストマー（二液硬化
性）〕、〕ダウコーニングＭＤＩ−４−４２１０（商品
名、メディカルグレードエラストマー（二液硬化性）〕
、〕ダウコーニングＭＤＩ−４−４５１４（商品名、メ
ディカルグレードエラストマー（二液硬化性）〕などが
好ましい。Silicone elastomers are elastomers made of silicone polymers such as polymethylsiloxane and dimethylmethylvinylsiloxane copolymers, such as Silastic 382 manufactured by Dow Corning ■.
[Product name, medical grade elastomer (two-component curable)],] Dow Corning MDI-4-4210 (trade name, medical grade elastomer (two-component curable)]
,] Dow Corning MDI-4-4514 (trade name, medical grade elastomer (two-component curable)) and the like are preferred.
複合体とは、薬物と水溶性高分子化合物が混溶状態を示
して、前者が元来アモルファス状の後者中に溶解したの
と同様にアモルファス状となって分散し、且つ各構成成
分の融点とは異なる特有の融点を示す混溶体または混合
体をいう。A complex is a state in which a drug and a water-soluble polymer compound are mixed, and the former is dispersed in an amorphous state in the same way as it was dissolved in the latter, which is originally amorphous, and the melting point of each component is It refers to a mixed solution or mixture that exhibits a unique melting point different from that of
本発明の経皮吸収剤は、たとえば以下の方法によって製
造することができる。The transdermal absorption agent of the present invention can be produced, for example, by the following method.
すなわち、薬物と水溶性高分子化合物を秤取し、（イ）
両者を共通の良溶媒に溶解した後、その溶媒を留去する
か：
（ロ）両者を一方の融点以上の温度に加熱し、一方の溶
融液中に他方を混溶させた後、冷却固化させるか；
（ハ）固体状の両者をコロイドミルのような粉挽機で粉
砕混合する
ことによシ複合体を調製する。That is, the drug and water-soluble polymer compound are weighed out, and (a)
Either dissolve both in a common good solvent and then distill off the solvent: (b) Heat both to a temperature higher than the melting point of one, mix the other in the molten liquid, and then cool and solidify. (c) A composite is prepared by grinding and mixing the two solids in a grinder such as a colloid mill.
この複合体を二液硬化性シリコーンポリマー（液状）と
均一に混合する。この際、必要に応じて可塑剤〔たとえ
ば、サイラスティック３６０（商品名、ダウ コーニン
グ社製の液状シリコーン）など〕、吸収促進剤（たとえ
ばイングロビルミリステート、エイシン、尿素、乳酸、
グリセリン。This composite is uniformly mixed with a two-part curable silicone polymer (liquid). At this time, if necessary, a plasticizer (for example, Silastic 360 (trade name, liquid silicone manufactured by Dow Corning), etc.), an absorption enhancer (for example, Inglobil myristate, Eisin, urea, lactic acid,
Glycerin.
モノグリセライド、ジイソプロピルアジペートなど）、
充填剤（たとえば、シリカ、炭酸カルシウム、タルク、
カオリンなど）を配合することができる。monoglyceride, diisopropyl adipate, etc.),
Fillers (e.g. silica, calcium carbonate, talc,
kaolin, etc.) can be blended.
この混合物に触媒（たとえば、オクタン酸錫など）を適
宜添加してすばやく十分に混合し、適宜の型にいれて室
温で、または加温して硬化させて本発明の経皮吸収剤を
得る。A catalyst (for example, tin octoate) is suitably added to this mixture, the mixture is quickly and thoroughly mixed, and the mixture is put into an appropriate mold and cured at room temperature or by heating to obtain the transdermal absorption agent of the present invention.
本発明の経皮吸収剤は、薬物０，０５〜１０部。The transdermal absorption agent of the present invention contains 0.05 to 10 parts of drug.
水溶性高分子化合物１〜３０部、シリコーンエラストマ
ー２０〜８０部、可塑剤１〜２０部、吸収イ足准右１１
〜５ 実状−を熾各１１０〜４０ 郁−触〃１ ４商当
量の範囲の組成で製造することが好ましい。1 to 30 parts of water-soluble polymer compound, 20 to 80 parts of silicone elastomer, 1 to 20 parts of plasticizer, 11 parts of absorbent
It is preferable to produce the composition in a range of 110 to 40 1 to 4 commercial equivalents.
本発明の経皮吸収剤においては、薬物は水溶性高分子化
合物と複合体を生成して、アモルファス状として存在す
ることによシ、その放出性を高めている。In the transdermal absorption agent of the present invention, the drug forms a complex with a water-soluble polymer compound and exists in an amorphous form, thereby improving its release properties.
このことは、後記試験例において、本発明の経皮吸収剤
と同一組成の経皮吸収剤であっても、薬物が水溶性高分
子化合物と複合体を生成しないものは、その薬物の放出
性が本発明の経皮吸収剤のそれよシ劣っていることから
明らかである。This means that in the test examples described later, even if the transdermal absorbent has the same composition as the transdermal absorbent of the present invention, if the drug does not form a complex with the water-soluble polymer compound, the release rate of the drug will be It is clear that this is inferior to that of the transdermal absorption agent of the present invention.
以上のように、本発明の経皮吸収剤は、薬物の放出性が
高く、皮膚または粘膜を経由して、必要十分量の薬物を
吸収させることができるので、適用が容易で、副作用の
発現を抑制すると 、とが可能である。As described above, the transdermal absorption agent of the present invention has high drug release properties and can absorb a necessary and sufficient amount of drug through the skin or mucous membranes, so it is easy to apply and does not cause side effects. By suppressing , it is possible to .
以下、実施例および試験例を挙げて本発明を具体的に説
明する。The present invention will be specifically described below with reference to Examples and Test Examples.
実施例 １
インドメタシン１．Ｏｆとポリビニルピロリドンに９０
５．Ｏｆとをメタノール５ｏ−に加えて溶解し、このメ
タノール溶液を減圧濃縮して液状の複合体を得た。これ
にサイラスティック３８２ ６０．０２、イソプロピル
ミリステート５．Ｏｆ、 サイラスティック５６０ ５
．０？、シリカ２３．５ Ｆを加えて攪拌混合機を用い
て均一に混合した後、これにオクタン酸銀０，５２を加
えてすばやく均一に混合し、型にいれて室温で１０分間
放置して硬化させ、本発明の経皮吸収剤を得た。Example 1 Indomethacin 1. 90 to Of and polyvinylpyrrolidone
5. Of was added to methanol 5o- to dissolve it, and the methanol solution was concentrated under reduced pressure to obtain a liquid complex. Add to this Silastic 382 60.02, Isopropyl Myristate 5. Of, Silastic 560 5
．． 0? , silica 23.5 F was added and mixed uniformly using a stirring mixer, then silver octoate 0.52 was added thereto and mixed quickly and uniformly, placed in a mold and left at room temperature for 10 minutes to harden. The transdermal absorption agent of the present invention was obtained.
実施例 ２
青草酸ベタメタシン０．０５ ｆとカルボキシメチルセ
ルロースナトリウム７、Ｏｆとを振動型コロイドミルを
用いて２時間混合粉砕して、粉末状の複合体を得た。Example 2 A powdery composite was obtained by mixing and pulverizing 0.05 f of betamethacin hydrochloride and 7, Of sodium carboxymethyl cellulose using a vibrating colloid mill for 2 hours.
この粉末状複合体は、示差熱量計を用いた融点測定では
青草酸ベタメタシンの融点の１９０℃のピークが消失し
ており、複合体を形成していることが判明した。When the melting point of this powdered composite was measured using a differential calorimeter, the peak at 190° C. of the melting point of betamethacin cyanobacterium disappeared, and it was found that a composite was formed.
この複合体混合物にサイラスティック３８２６５、Ｏｆ
、イソプロピルミリステート２、ｏグ、サイラスティッ
ク３６０ １５．Ｏｒ、シリカ１０．４５Ｓ’を加えて
攪拌混合機を用いて均一に混合した後、これにオクタン
酸銀ｏ、５１を加えて、すばやく均一に混合し、型にい
れて室温で１０分間放置して硬化させ、本発明の経皮吸
収剤を得た。Silastic 38265, Of
, Isopropyl Myristate 2, Og, Silastic 360 15. Or, silica 10.45S' was added and mixed uniformly using a stirring mixer, then silver octoate O, 51 was added thereto, mixed quickly and uniformly, and placed in a mold and left at room temperature for 10 minutes. The transdermal absorption agent of the present invention was obtained by curing.
試験例 １
試料１および２はオクタン酸銀以外の成分を攪拌混合機
を用いて均一に混合後、オクタン酸銀を加えてすばやく
均一に混合し、型にいれて室温で１０分間放置して硬化
させることによシ調製した。Test Example 1 Samples 1 and 2 were prepared by uniformly mixing the components other than silver octoate using a stirring mixer, then adding silver octoate and quickly and uniformly mixing, placing in a mold and leaving at room temperature for 10 minutes to harden. It was prepared by letting.
試料３は実施例１で調製した試料を用いた。各試料から
２ ｃｍ Ｘ ５ ｃｍ Ｘ Ｏ，５ｃｍのブロックを
切り取り、各ブロックをそれぞれ水２００−をいれた容
器にいれ、Ｋｙｅｌａ Ｂａｔｈ ５Ｂ−２４振盪機（
アイラ社製）を用いて振盪し、時間経過によるイ〉ドメ
タシンの累積放出量を紫外線吸収法により測定した。Sample 3 used the sample prepared in Example 1. Cut 2 cm x 5 cm x O, 5 cm blocks from each sample, place each block in a container containing 200ml of water, and place in a Kyela Bath 5B-24 shaker (
(manufactured by Aira) and the cumulative amount of idomethacin released over time was measured by ultraviolet absorption method.
その結果を第１図に示す。第１図においてＡ。The results are shown in FIG. A in FIG.
Ｂ、Ｏはそれぞれ資料１．２．５の経時的な累積放出量
を示す。第１図は試料６の薬物放出性が試料１および２
のそれに比較して非常に高く、まだ、その直線的な累積
放出量より試料３の薬物放出制御が損なわれていないこ
とを表わす。B and O indicate the cumulative release amount over time of Document 1.2.5, respectively. Figure 1 shows that the drug release properties of sample 6 are different from those of samples 1 and 2.
is very high compared to that of , indicating that the drug release control of sample 3 is still intact than its linear cumulative release amount.
試験例 ２
試料４および５は試験例１の試料１および２に準じて調
製し、試料６は実施例２で調製した試料を用いた。Test Example 2 Samples 4 and 5 were prepared according to Samples 1 and 2 of Test Example 1, and Sample 6 was the sample prepared in Example 2.
各試料を用いて試験例１と同様にして時間経過による吉
草酸ベタメタシンの累積放出量を測定した。Using each sample, the cumulative release amount of betamethacin valerate over time was measured in the same manner as in Test Example 1.
その結果を第２図に示す。第２図において、Ｄ。The results are shown in FIG. In FIG. 2, D.
Ｆｌｊ、Ｆはそれぞれ資料４．５．６の経時的な累積放
出量を示す。第２図は、試料乙の薬物放出性が試料４お
よび５のそれに比較すると非常に高く、また、その直線
的な累積放出量よシ試料乙の薬物放出制御が損なわれて
いないことを表わす。Flj and F each indicate the cumulative release amount over time of Document 4.5.6. FIG. 2 shows that the drug release property of Sample B is very high compared to that of Samples 4 and 5, and that the drug release control of Sample B is not impaired due to its linear cumulative release amount.
第１図は、本発明の一実施態様である経皮吸収剤（試験
例１の試料３）および対照経皮吸収剤（試験例１の試料
１および２）における、インドメタシンの経時的な累積
放出量を示し、第２図は、本発明の他の実施態様である
経皮吸収タメタゾンの経時的な累積放出量を示す。
図面において、Ａ、Ｂ、Ｃはそれぞれ試験例１の試料１
，２．’３を示し、Ｉ）、Ｅ、Ｆはそれぞれ試験例２の
試料４．５．６を示す。
特許出願人 大正製薬株式会社
代理人 弁理士 北 川 富 造Figure 1 shows the cumulative release of indomethacin over time in a transdermal absorbent that is an embodiment of the present invention (Sample 3 of Test Example 1) and a control transdermal absorbent (Samples 1 and 2 of Test Example 1). Figure 2 shows the cumulative release over time of transdermal tametasone, another embodiment of the invention. In the drawings, A, B, and C are Sample 1 of Test Example 1, respectively.
,2. '3, and I), E, and F each represent sample 4.5.6 of Test Example 2. Patent applicant Taisho Pharmaceutical Co., Ltd. Agent Patent attorney Tomizo Kitagawa
Claims (1)
ラストマーからなる基剤に分散した経皮吸収剤。1) A transdermal absorption agent in which a complex of a drug and a water-soluble polymer compound is dispersed in a base made of silicone elastomer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59024421A JPS60169414A (en) | 1984-02-14 | 1984-02-14 | Endermic absorption agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP59024421A JPS60169414A (en) | 1984-02-14 | 1984-02-14 | Endermic absorption agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS60169414A true JPS60169414A (en) | 1985-09-02 |
| JPH0339486B2 JPH0339486B2 (en) | 1991-06-14 |
Family
ID=12137688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP59024421A Granted JPS60169414A (en) | 1984-02-14 | 1984-02-14 | Endermic absorption agent |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS60169414A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0201828A2 (en) * | 1985-05-11 | 1986-11-20 | Bayer Ag | Components for therapeutical drug delivery devices |
| US5613958A (en) * | 1993-05-12 | 1997-03-25 | Pp Holdings Inc. | Transdermal delivery systems for the modulated administration of drugs |
| JP2011521974A (en) * | 2008-05-30 | 2011-07-28 | マイラン・インコーポレーテッド | Stabilized transdermal drug delivery system |
| US8173113B1 (en) | 1989-11-03 | 2012-05-08 | 3M Innovative Properties Company | Bioadhesive composition and patch |
-
1984
- 1984-02-14 JP JP59024421A patent/JPS60169414A/en active Granted
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0201828A2 (en) * | 1985-05-11 | 1986-11-20 | Bayer Ag | Components for therapeutical drug delivery devices |
| US8173113B1 (en) | 1989-11-03 | 2012-05-08 | 3M Innovative Properties Company | Bioadhesive composition and patch |
| US5613958A (en) * | 1993-05-12 | 1997-03-25 | Pp Holdings Inc. | Transdermal delivery systems for the modulated administration of drugs |
| JP2011521974A (en) * | 2008-05-30 | 2011-07-28 | マイラン・インコーポレーテッド | Stabilized transdermal drug delivery system |
| US9226902B2 (en) | 2008-05-30 | 2016-01-05 | Mylan Technologies Inc. | Stabilized transdermal drug delivery system |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0339486B2 (en) | 1991-06-14 |
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| EXPY | Cancellation because of completion of term |