CN1387847A - Lefunomide plaster and its prepn - Google Patents
Lefunomide plaster and its prepn Download PDFInfo
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- CN1387847A CN1387847A CN 02112476 CN02112476A CN1387847A CN 1387847 A CN1387847 A CN 1387847A CN 02112476 CN02112476 CN 02112476 CN 02112476 A CN02112476 A CN 02112476A CN 1387847 A CN1387847 A CN 1387847A
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- leflunomide
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- cataplasm
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- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 239000011505 plaster Substances 0.000 title 1
- 229960000681 leflunomide Drugs 0.000 claims abstract description 31
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 11
- 108010010803 Gelatin Proteins 0.000 claims abstract description 10
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000008273 gelatin Substances 0.000 claims abstract description 10
- 229920000159 gelatin Polymers 0.000 claims abstract description 10
- 235000019322 gelatine Nutrition 0.000 claims abstract description 10
- 235000011852 gelatine desserts Nutrition 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 239000005995 Aluminium silicate Substances 0.000 claims abstract description 7
- 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 claims abstract description 7
- 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 claims abstract description 7
- 235000012211 aluminium silicate Nutrition 0.000 claims abstract description 7
- 239000001768 carboxy methyl cellulose Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 7
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 claims abstract description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims abstract description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims abstract description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims abstract description 7
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims abstract description 7
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims abstract description 7
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 claims abstract description 7
- 239000000600 sorbitol Substances 0.000 claims abstract description 7
- 239000002313 adhesive film Substances 0.000 claims abstract description 5
- 230000000181 anti-adherent effect Effects 0.000 claims abstract description 5
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 5
- 239000011159 matrix material Substances 0.000 claims abstract description 5
- 239000004745 nonwoven fabric Substances 0.000 claims abstract description 5
- 235000010356 sorbitol Nutrition 0.000 claims abstract description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims abstract 2
- 238000003756 stirring Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 229920002521 macromolecule Polymers 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 7
- 229920003169 water-soluble polymer Polymers 0.000 abstract description 4
- 206010067484 Adverse reaction Diseases 0.000 abstract description 3
- 230000006838 adverse reaction Effects 0.000 abstract description 3
- 239000002552 dosage form Substances 0.000 abstract description 2
- 229960003444 immunosuppressant agent Drugs 0.000 abstract description 2
- 230000001861 immunosuppressant effect Effects 0.000 abstract description 2
- 239000003018 immunosuppressive agent Substances 0.000 abstract description 2
- 230000035699 permeability Effects 0.000 abstract description 2
- 206010061218 Inflammation Diseases 0.000 abstract 1
- 229920006037 cross link polymer Polymers 0.000 abstract 1
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 abstract 1
- 239000007935 oral tablet Substances 0.000 abstract 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000005577 Gastroenteritis Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000000947 anti-immunosuppressive effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 150000002545 isoxazoles Chemical class 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
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- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
本发明涉及医药技术领域,是免疫抑制剂来氟米特的一种新剂型——巴布剂及其制备方法。本发明巴布剂的基质成分包括水溶性高分子化合物明胶、羧甲基纤维素钠、聚乙烯吡咯烷酮、山梨醇、聚丙烯酸钠、高岭土、丙二醇和交联剂戊二醛溶液。先将水溶性高分子化合物分两组分别制成I相溶液和II相溶液,药物来氟米特的加入与制备II相溶液同时进行,再将I、II相溶液混合均匀后加交联剂戊二醛溶液,使高分子化合物相互交联形成凝胶骨架型基质,然后铺于无纺布上,盖上防粘膜,烘干后即得来氟米特巴布剂。本巴布剂载药量大,透气性好,皮肤粘着性适宜,不仅避免了来氟米特口服片剂对胃肠道带来的各种不良反应,而且由于提高了炎症部位的药物浓度而增强了疗效。The invention relates to the technical field of medicine, and relates to a new dosage form of the immunosuppressant leflunomide, a cataplasm and a preparation method thereof. The matrix components of the cataplasm of the present invention include water-soluble polymer compound gelatin, sodium carboxymethylcellulose, polyvinylpyrrolidone, sorbitol, sodium polyacrylate, kaolin, propylene glycol and crosslinking agent glutaraldehyde solution. First divide the water-soluble polymer compound into two groups to make phase I solution and phase II solution respectively, add the drug leflunomide and prepare the phase II solution at the same time, then mix the phase I and II solutions evenly, and then add the cross-linking agent glutaraldehyde solution to cross-link polymer compounds to form a gel-skeleton matrix, and then spread it on a non-woven fabric, cover it with an anti-adhesive film, and dry it to obtain the leflunomide poultice. This cataplasm has a large drug loading capacity, good air permeability, and suitable skin adhesion, which not only avoids various adverse reactions caused by leflunomide oral tablets on the gastrointestinal tract, but also increases the concentration of the drug in the inflammation site. Enhanced efficacy.
Description
技术领域：本发明涉及医药技术领域，是免疫抑制剂来氟米特的一种新剂型一巴布剂及其制备方法。Technical field: the present invention relates to the technical field of medicine, and is a new dosage form of the immunosuppressant leflunomide, a cataplasm and a preparation method thereof.
背景技术：来氟米特(Leflunomide)是一种具有抗炎及免疫抑制作用的异噁唑类衍生物，对治疗类风湿性关节炎效果显著，目前仅有片剂，不良反应以厌食、腹痛、腹泻、恶心、呕吐、胃炎及胃肠炎等胃肠道症状和肝功能损害为最常见，为提高来氟米特在炎性关节局部的药物浓度、增强抗炎作用、减少全身给药引起的不良反应，研究局部使用的来氟米特经皮给药制剂是很有意义的。Background technology: Leflunomide (Leflunomide) is an isoxazole derivative with anti-inflammatory and immunosuppressive effects. It has a significant effect on the treatment of rheumatoid arthritis. At present, there are only tablets. The adverse reactions include anorexia and abdominal pain. Gastrointestinal symptoms such as diarrhea, nausea, vomiting, gastritis and gastroenteritis, and liver function damage are the most common. In order to increase the local drug concentration of leflunomide in inflammatory joints, enhance anti-inflammatory effects, and reduce systemic administration It is of great significance to study the topical leflunomide transdermal formulation.
发明内容：本发明将来氟米特制成巴布剂，巴布剂载药量大，透气性好，对皮肤粘着性好。通常来氟米特治疗剂量较大，制备来氟米特巴布剂不仅提高了来氟米特在炎性关节局部的药物浓度、增强抗炎作用，而且降低了来氟米特血药浓度的波动，从而减少了药物引起的不良反应。本发明巴布剂的配方及配比为：水溶性高分子化合物明胶0.5g、羧甲基纤维素钠1g、聚乙烯吡咯烷酮1.75g、山梨醇10g、聚丙烯酸钠0.125-0.5g、高岭土1-2g、丙二醇5-10ml和交联剂25％戊二醛溶液3.5ml。先将水溶性高分子化合物分两组分别制成I相溶液和II相溶液，药物来氟米特的加入与制备II相溶液同时进行，再将I、II相溶液混合均匀后加交联剂戊二醛溶液，使高分子化合物相互交联形成凝胶骨架型基质。具体制备方法为：Summary of the invention: In the present invention, leflunomide is made into a cataplasm, which has a large drug-loading capacity, good air permeability, and good adhesion to the skin. Usually the treatment dose of leflunomide is relatively large, and the preparation of leflunomide cataplasm not only improves the local drug concentration of leflunomide in inflammatory joints, enhances the anti-inflammatory effect, but also reduces the blood concentration of leflunomide. Fluctuations, thereby reducing adverse reactions caused by drugs. The formula and proportioning of the cataplasm of the present invention are: 0.5 g of water-soluble polymer compound gelatin, 1 g of sodium carboxymethyl cellulose, 1.75 g of polyvinylpyrrolidone, 10 g of sorbitol, 0.125-0.5 g of sodium polyacrylate, and 1-g of kaolin. 2g, 5-10ml of propylene glycol and 3.5ml of 25% glutaraldehyde solution of crosslinking agent. First divide the water-soluble polymer compound into two groups to make phase I solution and phase II solution respectively, add the drug leflunomide and prepare the phase II solution at the same time, then mix the phase I and II solutions evenly before adding the crosslinking agent Glutaraldehyde solution cross-links polymer compounds to form a gel-skeleton matrix. The specific preparation method is:
1.制备I相溶液：在50℃水浴下将明胶充分溶解于水中，再将羧甲基纤维素钠、聚乙烯吡咯烷酮、山梨醇混合均匀后加入明胶溶液中，加水充分溶胀即得I相溶液。1. Prepare phase I solution: fully dissolve gelatin in water in a water bath at 50°C, then mix sodium carboxymethylcellulose, polyvinylpyrrolidone, and sorbitol evenly, add to the gelatin solution, add water to fully swell to obtain phase I solution .
2.制备II相溶液：将来氟米特与聚丙烯酸钠、高岭土一起分散于丙二醇中，搅拌均匀即得II相溶液。2. Preparation of phase II solution: disperse leflunomide, sodium polyacrylate and kaolin in propylene glycol, and stir evenly to obtain phase II solution.
3.制备来氟米特巴布剂：将II相溶液加入I相溶液中，搅拌混匀后得到均匀粘稠膏体；将戊二醛溶液加入该膏体中，搅拌，充分交联后铺于无纺布上，盖上防粘膜，烘干后即得来氟米特巴布剂。3. Preparation of leflunomide poultice: add phase II solution to phase I solution, stir and mix to obtain a uniform viscous paste; add glutaraldehyde solution to the paste, stir, fully cross-link and spread Cover the non-woven fabric with an anti-adhesive film, and dry it to obtain the leflunomide poultice.
具体实施方式：Detailed ways:
实施例1：制备来氟米特巴布剂Embodiment 1: preparation leflunomide cataplasm
配方及其配比：
1.制备I相溶液：在50℃水浴下将明胶充分溶解于水中，再将羧甲基纤维素钠、聚乙烯吡咯烷酮、山梨醇混合均匀后加入明胶溶液中，加水充分溶胀即得I相溶液；1. Prepare phase I solution: fully dissolve gelatin in water in a water bath at 50°C, then mix sodium carboxymethylcellulose, polyvinylpyrrolidone, and sorbitol evenly, add to the gelatin solution, add water to fully swell to obtain phase I solution ;
2.制备II相溶液：将来氟米特和聚丙烯酸钠、高岭土一起分散于丙二醇中，搅拌均匀即得II相溶液；2. Preparation of phase II solution: disperse leflunomide, sodium polyacrylate and kaolin in propylene glycol, and stir evenly to obtain phase II solution;
3.制备来氟米特巴布剂：将II相溶液加入I相溶液中，搅拌混匀后得到均匀粘稠膏体；将戊二醛溶液加入该膏体中，搅拌，充分交联后铺于无纺布上约400cm2，盖上防粘膜。置烘箱中60℃干燥12小时，即得来氟米特巴布剂。将其裁成5片，每片含来氟米特100mg。3. Preparation of leflunomide poultice: add phase II solution to phase I solution, stir and mix to obtain a uniform viscous paste; add glutaraldehyde solution to the paste, stir, fully cross-link and spread About 400cm2 on the non-woven fabric, covered with anti-adhesive film. Dry it in an oven at 60°C for 12 hours to obtain Leflunomide cataplasm. Cut it into 5 pieces, each containing 100mg of leflunomide.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021124760A CN1161119C (en) | 2002-07-11 | 2002-07-11 | Leflunomide cataplasm and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021124760A CN1161119C (en) | 2002-07-11 | 2002-07-11 | Leflunomide cataplasm and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1387847A true CN1387847A (en) | 2003-01-01 |
| CN1161119C CN1161119C (en) | 2004-08-11 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB021124760A Expired - Fee Related CN1161119C (en) | 2002-07-11 | 2002-07-11 | Leflunomide cataplasm and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1161119C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008040149A1 (en) * | 2006-09-05 | 2008-04-10 | Dexian Dou | Composition and method for treating immune-mediated skin disorders |
| CN100502852C (en) * | 2003-04-17 | 2009-06-24 | 中国人民解放军第二军医大学 | Flurbiprofen cataplasm and preparation method thereof |
| US9278155B2 (en) | 2003-06-05 | 2016-03-08 | 3M Innovative Properties Company | Adhesive compositions, articles incorporating same and methods of manufacture |
-
2002
- 2002-07-11 CN CNB021124760A patent/CN1161119C/en not_active Expired - Fee Related
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100502852C (en) * | 2003-04-17 | 2009-06-24 | 中国人民解放军第二军医大学 | Flurbiprofen cataplasm and preparation method thereof |
| US9278155B2 (en) | 2003-06-05 | 2016-03-08 | 3M Innovative Properties Company | Adhesive compositions, articles incorporating same and methods of manufacture |
| WO2008040149A1 (en) * | 2006-09-05 | 2008-04-10 | Dexian Dou | Composition and method for treating immune-mediated skin disorders |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1161119C (en) | 2004-08-11 |
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Granted publication date: 20040811 Termination date: 20100711 |