CN113069437A - 一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂及其制备方法 - Google Patents
一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂及其制备方法 Download PDFInfo
- Publication number
- CN113069437A CN113069437A CN202011608898.2A CN202011608898A CN113069437A CN 113069437 A CN113069437 A CN 113069437A CN 202011608898 A CN202011608898 A CN 202011608898A CN 113069437 A CN113069437 A CN 113069437A
- Authority
- CN
- China
- Prior art keywords
- loxoprofen
- styrene
- copolymer
- graft
- gel 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
- 229960002373 loxoprofen Drugs 0.000 title claims abstract description 40
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 title claims abstract description 40
- 150000003839 salts Chemical class 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000011505 plaster Substances 0.000 claims abstract description 27
- 239000011347 resin Substances 0.000 claims abstract description 19
- 229920005989 resin Polymers 0.000 claims abstract description 19
- 239000000945 filler Substances 0.000 claims abstract description 16
- 239000012528 membrane Substances 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 229920002472 Starch Polymers 0.000 claims description 18
- 239000008107 starch Substances 0.000 claims description 18
- 235000019698 starch Nutrition 0.000 claims description 18
- 239000001913 cellulose Substances 0.000 claims description 15
- 229920002678 cellulose Polymers 0.000 claims description 15
- -1 acrylate compound Chemical class 0.000 claims description 12
- 229920002125 Sokalan® Polymers 0.000 claims description 11
- 229920000578 graft copolymer Polymers 0.000 claims description 11
- 229920001577 copolymer Polymers 0.000 claims description 10
- 238000010521 absorption reaction Methods 0.000 claims description 9
- 239000011248 coating agent Substances 0.000 claims description 9
- 238000000576 coating method Methods 0.000 claims description 9
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 9
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 8
- 239000004584 polyacrylic acid Substances 0.000 claims description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 6
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 6
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 230000003078 antioxidant effect Effects 0.000 claims description 6
- 238000004132 cross linking Methods 0.000 claims description 6
- 210000004379 membrane Anatomy 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 239000008213 purified water Substances 0.000 claims description 6
- VSKJLJHPAFKHBX-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1.C=CC1=CC=CC=C1 VSKJLJHPAFKHBX-UHFFFAOYSA-N 0.000 claims description 5
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 5
- 239000003431 cross linking reagent Substances 0.000 claims description 5
- 239000003623 enhancer Substances 0.000 claims description 5
- 239000003906 humectant Substances 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 4
- 238000005520 cutting process Methods 0.000 claims description 4
- 229940124274 edetate disodium Drugs 0.000 claims description 4
- ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical compound CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- 239000012991 xanthate Substances 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- FACXGONDLDSNOE-UHFFFAOYSA-N buta-1,3-diene;styrene Chemical compound C=CC=C.C=CC1=CC=CC=C1.C=CC1=CC=CC=C1 FACXGONDLDSNOE-UHFFFAOYSA-N 0.000 claims description 3
- MTAZNLWOLGHBHU-UHFFFAOYSA-N butadiene-styrene rubber Chemical class C=CC=C.C=CC1=CC=CC=C1 MTAZNLWOLGHBHU-UHFFFAOYSA-N 0.000 claims description 3
- 229920006132 styrene block copolymer Polymers 0.000 claims description 3
- 229920003048 styrene butadiene rubber Polymers 0.000 claims description 3
- 229920000468 styrene butadiene styrene block copolymer Polymers 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
- KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 claims description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 claims description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 2
- XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- CYKDLUMZOVATFT-UHFFFAOYSA-N ethenyl acetate;prop-2-enoic acid Chemical compound OC(=O)C=C.CC(=O)OC=C CYKDLUMZOVATFT-UHFFFAOYSA-N 0.000 claims description 2
- 239000000835 fiber Substances 0.000 claims description 2
- 210000004400 mucous membrane Anatomy 0.000 claims description 2
- 229920000098 polyolefin Polymers 0.000 claims description 2
- 238000007873 sieving Methods 0.000 claims description 2
- 229940042129 topical gel Drugs 0.000 claims 9
- 239000003607 modifier Substances 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 229920000642 polymer Polymers 0.000 claims 1
- 239000002674 ointment Substances 0.000 abstract description 12
- 239000003814 drug Substances 0.000 abstract description 9
- 239000011256 inorganic filler Substances 0.000 abstract description 7
- 239000000463 material Substances 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 abstract description 5
- 239000011707 mineral Substances 0.000 abstract description 5
- 239000012764 mineral filler Substances 0.000 abstract description 3
- 239000000499 gel Substances 0.000 description 36
- 239000000243 solution Substances 0.000 description 17
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 16
- 235000012211 aluminium silicate Nutrition 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 239000005995 Aluminium silicate Substances 0.000 description 7
- 230000000052 comparative effect Effects 0.000 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 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 229920002126 Acrylic acid copolymer Polymers 0.000 description 5
- 229910003475 inorganic filler Inorganic materials 0.000 description 5
- 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 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 0.000 description 4
- 229960005070 ascorbic acid Drugs 0.000 description 4
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 4
- 229940068984 polyvinyl alcohol Drugs 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 239000011975 tartaric acid Substances 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 3
- 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 description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 3
- VIZORQUEIQEFRT-UHFFFAOYSA-N Diethyl adipate Chemical compound CCOC(=O)CCCCC(=O)OCC VIZORQUEIQEFRT-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- DGVMNQYBHPSIJS-UHFFFAOYSA-N dimagnesium;2,2,6,6-tetraoxido-1,3,5,7-tetraoxa-2,4,6-trisilaspiro[3.3]heptane;hydrate Chemical compound O.[Mg+2].[Mg+2].O1[Si]([O-])([O-])O[Si]21O[Si]([O-])([O-])O2 DGVMNQYBHPSIJS-UHFFFAOYSA-N 0.000 description 3
- 229940041616 menthol Drugs 0.000 description 3
- 239000004745 nonwoven fabric Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-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
- 108010010803 Gelatin Proteins 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229940024545 aluminum hydroxide Drugs 0.000 description 2
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 2
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000001087 glyceryl triacetate Substances 0.000 description 2
- 235000013773 glyceryl triacetate Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 201000008482 osteoarthritis Diseases 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 229920001083 polybutene Polymers 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960001367 tartaric acid Drugs 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 230000037317 transdermal delivery Effects 0.000 description 2
- 229960002622 triacetin Drugs 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-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
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- ZUGAOYSWHHGDJY-UHFFFAOYSA-K 5-hydroxy-2,8,9-trioxa-1-aluminabicyclo[3.3.2]decane-3,7,10-trione Chemical compound [Al+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O ZUGAOYSWHHGDJY-UHFFFAOYSA-K 0.000 description 1
- ODHCTXKNWHHXJC-VKHMYHEASA-M 5-oxo-L-prolinate Chemical compound [O-]C(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-M 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 239000004971 Cross linker Substances 0.000 description 1
- 229920000832 Cutin Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 241001478425 Hippocampus japonicus Species 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- HDVDLQFPDLTOSI-UHFFFAOYSA-L O[AlH]O Chemical compound O[AlH]O HDVDLQFPDLTOSI-UHFFFAOYSA-L 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002367 Polyisobutene Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920000297 Rayon Polymers 0.000 description 1
- 240000007994 Rhodomyrtus tomentosa Species 0.000 description 1
- 235000007234 Rhodomyrtus tomentosa Nutrition 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 229920001938 Vegetable gum Polymers 0.000 description 1
- UJNOLBSYLSYIBM-WISYIIOYSA-N [(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl] (2r)-2-hydroxypropanoate Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)[C@@H](C)O UJNOLBSYLSYIBM-WISYIIOYSA-N 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- HZVVJJIYJKGMFL-UHFFFAOYSA-N almasilate Chemical compound O.[Mg+2].[Al+3].[Al+3].O[Si](O)=O.O[Si](O)=O HZVVJJIYJKGMFL-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940063656 aluminum chloride Drugs 0.000 description 1
- 229940103272 aluminum potassium sulfate Drugs 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229960001777 castor oil Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000022371 chronic pain syndrome Diseases 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- DNTGGZPQPQTDQF-XBXARRHUSA-N crotamiton Chemical compound C/C=C/C(=O)N(CC)C1=CC=CC=C1C DNTGGZPQPQTDQF-XBXARRHUSA-N 0.000 description 1
- 229960003338 crotamiton Drugs 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940031578 diisopropyl adipate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229960003639 laurocapram Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 1
- 229960001173 oxybenzone Drugs 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 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
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940071139 pyrrolidone carboxylate Drugs 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000002964 rayon Substances 0.000 description 1
- 239000005060 rubber Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂及其制备方法,属于洛索洛芬类外用凝胶贴膏剂领域。本发明要解决以无机类(或矿物类)作为填充剂导致了凝胶贴膏的膏体偏硬、黏性偏低、药物释放偏缓,以及不同产地的物料导致产品的不可重现性等技术问题;其由支持体、含药膏体层和防黏膜组成,采用有机类保水树脂作为含药膏体层的填充剂,其活性成分为洛索洛芬或其药学上可接受的盐。相对于以往采用无机类或矿物类填充剂的同类产品,本发明的产品具有更好的黏附性和透皮效果,从而实现更好的疗效。
Description
技术领域
本发明属于非甾体抗炎药的外用贴膏剂的技术领域;涉及一种含有非甾体抗炎药的外用凝胶贴膏剂及其制备方法,尤其涉及一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂,其由支持体、含药膏体层和防黏膜组成。
背景技术
凝胶贴膏剂曾被称作巴布膏剂或凝胶膏剂,系指原料药物与适宜的亲水性基质混匀后涂布于背衬材料上制成的贴膏剂。其特征在于,水分含有量高于传统中药膏药(橡胶贴膏剂),膏体具有适宜的厚度,与皮肤的亲和性优异,对皮肤的刺激性小于传统膏药。与口服给药方式比较,凝胶贴膏剂产品无须经过消化道,不受食物、胃液的影响和破坏,且可避免口服给药对胃肠黏膜和肝脏所造成的刺激和损害,适用于不宜接受口服给药的患者。凝胶贴膏剂于上世纪中后期,由日本制药公司研发成功并上市,近年来部分产品及相关技术引入我国。尤其是非甾体抗炎药的凝胶贴膏制剂已经在临床上被广泛用于治疗骨关节炎、肌肉痛等多种急慢性疼痛类疾病。洛索洛芬作为新型非甾体消炎药,是其中最新的药物成分。
与多数非甾体抗炎药直接发挥作用不同的是,洛索洛芬前体药物需从皮肤吸收后转换成活性代谢物反式-OH从而发挥消炎止痛作用,其在皮下组织、骨骼肌中浓度较高。洛索洛芬的这一特性决定了其可作为优良的外用凝胶贴膏制剂的成分。洛索洛芬凝胶贴膏最初由日本利德化学株式会社开发成功,并于2006年在日本获批上市。洛索洛芬凝胶贴膏在日本上市多年来,已成为临床上的常用药物,主要用于治疗骨关节炎、肌肉痛,以及外伤所致肿胀、疼痛。
在凝胶贴膏剂的发展历程中,长期以来都是以高岭土、硅藻土、膨润土、白陶土、碳酸钙、氧化锌、微粉硅胶、二氧化硅等为主要的填充介质。这些无机类(或矿物类)填充剂使得凝胶贴膏具有一定的成型性,同时也导致了产品的膏体偏硬、黏性偏低、药物释放偏缓,以及不同产地的物料导致产品的不可重现性等。
以矿物类填充剂高岭土为例,如下述专利文献1及专利文献2所述,以往制备凝胶贴膏剂时常用无机物(矿物质)作为填充剂。但如下述文献3及文献4所述,不同国家不同产地的高岭土间存在较大差异,甚至同一国家内部不同产地的高岭土间也存在一定差异。研究人员发现使用了日本广岛产的高岭土会使凝胶贴膏变硬,使用不便,而使用了日本福岛产的高岭土的凝胶贴膏则容易制备成功。因此,研究人员亟需寻找一种避免使用高岭土等无机类(或矿物类)填充剂,能稳定制备凝胶贴膏的方法。
另一方面,与传统膏药相比,凝胶贴膏剂产品通常含有大量水分,有的含水比例甚至超过50%(以膏体重量计)。而由于传统高岭土等无机物质类填充剂吸水性一般,在制作凝胶贴膏剂产品时,无机填充剂加入量过少则容易导致凝胶贴膏剂产品的膏体偏软,容易溢出防粘膜或支持体,贴付舒适性差;加入量过多则容易产生凝胶贴膏剂膏体变硬,膏体成形性差,透皮吸收率低等问题。与无机填充剂相比,保水树脂如淀粉接枝丙烯酸共聚物、纤维素接枝丙烯酸共聚物、苯乙烯-异戊二烯-苯乙烯等具有强吸水性,如淀粉接枝丙烯酸共聚物的吸水倍率可接近1000,远优于无机填充剂类。且,凝胶贴膏制剂中通常还配伍使用较多比例的甘油。一种或一种以上保水树脂的联合使用可有效减少凝胶贴膏制剂中水及甘油等液体中水分过多导致的问题。因此,研究人员正在寻找一种使用保水树脂为填充剂,进行凝胶贴膏制备的方法。
专利文献
专利文献1:含有环氧洛芬的水性贴剂。CN101896175B。申请人:帝国制药株式会社,申请日:2008年12月11日。
专利文献2:含水性贴剂。CN103501779B。申请人:尼普洛外用药品株式会社。申请日:2012年1月23日。
文献3:カオリンパップの塑性粘度変動について。棚田成紀,榎本三郎。材料,1972年第21巻第225号:598-601。
文献4:成型パップ剤の製剤設計に関する研究。黒田稔。1986年日本岐阜药科大学学位论文。
发明内容
本发明要解决以无机类(或矿物类)作为填充剂导致了凝胶贴膏的膏体偏硬、黏性偏低、药物释放偏缓,以及不同产地的物料导致产品的不可重现性等技术问题;提供一种采用有机类保水树脂作为填充剂的洛索洛芬及其药用盐的凝胶贴膏剂。
为解决上述技术问题,通过下述技术方案实现:
本发明所述的含有保水树脂的凝胶贴膏剂是由支持体、含药膏体层和防黏膜组成。其中膏体层除了活性成分外,还含有保水树脂填充剂、增黏剂、交联剂及交联调节剂、吸收促进剂、保湿剂、抗氧化剂、pH调节剂等多种成分。
本发明所述的凝胶贴膏剂,以含药膏体层重量%计,含活性成分0.1重量%-10重量%,纯化水25重量%-75重量%,填充剂1重量%-40重量%,增黏剂1重量%-40重量%,交联剂及交联调节剂0.1重量%-10重量%,吸收促进剂0.1重量%-10重量%,保湿剂1重量%-40重量%,抗氧化剂0.1重量%-10重量%,和pH调节剂0.1重量%-10重量%;其中,填充剂为有机类保水树脂。
本发明所述的有机类保水树脂填充剂可选自淀粉接枝共聚物、聚丙烯酸类聚合物、聚乙烯醇类聚合物纤维素接枝共聚物以及苯乙烯类共聚物中的一种或其中的几种任意比的组合;
其中,所述淀粉接枝共聚物为淀粉接枝丙烯酸酯、淀粉接枝丙烯酰胺、淀粉接枝丙烯酸、淀粉接枝丙烯腈、淀粉黄原酸盐接枝丙烯酸盐等淀粉接枝共聚物;
所述聚丙烯酸类聚合物为聚丙烯酸盐、聚丙烯酸盐加聚烯烃、丙烯腈纤维与丙烯酸盐复合物、醋酸乙烯丙烯酸酯中的一种或其中的几种任意比的组合;
所述聚乙烯醇类聚合物为醋酸乙烯不饱和酸共聚物、醋酸乙烯丙烯酸酯共聚物、聚乙烯酸丙烯酰胺接枝共聚物、聚乙烯醇醋酐交联共聚物中的一种或其中的几种任意比的组合;
所述纤维素接枝共聚物为纤维素接枝丙烯酸盐、纤维素接枝丙烯腈、纤维素黄原酸盐接枝丙烯酸盐、纤维素接枝丙烯酰胺中的一种或其中的几种任意比的组合;
所述苯乙烯类共聚物为苯乙烯-异戊二烯-苯乙烯、苯乙烯-丁二烯-苯乙烯、氢化苯乙烯-丁二烯嵌段共聚物、苯乙烯-乙烯-丙烯-苯乙烯嵌段共聚物中的一种或其中的几种任意比的组合;
其中,有机类保水树脂优选为淀粉接枝丙烯酸共聚物、苯乙烯-异戊二烯-苯乙烯和纤维素接枝丙烯酸共聚物中的两种任意比的组合;
以含药膏体层重量%计,有机类保水树脂用量为1重量%-40重量%,优选为1重量%-20重量%。
本发明所述的增黏剂可选自羟乙纤维素、羟丙甲纤维素、羧甲纤维素钠等纤维素类及其衍生物,聚乙烯醇、聚乙烯吡咯烷酮、部分中和聚丙烯酸盐、聚丙烯酸或其水溶液、聚丁烯、聚异丁烯、聚丁烯酸等高分子合成材料,明胶、阿拉伯胶、黄原胶、瓜尔胶、西黄蓍胶等动植物胶等其中的一种或者其中的几种任意比的组合,其中优选为聚乙烯醇、明胶、聚丙烯酸、羧甲纤维素钠。以含药膏体层重量%计,有机类保水树脂用量为1重量%-40重量%,优选1重量%-20重量%。
本发明的交联剂及交联调节剂可选自氯化铝、硫酸铝钾、氢氧化铝、甘羟铝、合成硅酸铝、柠檬酸铝、硅铝酸镁、水硅酸镁、依地酸及其盐等其中的一种或其中的几种任意比的组合,其中优选为甘羟铝、氢氧化铝、依地酸钠。以含药膏体层重量%计,其含量为0.1重量%-10重量%,优选为0.1重量%-5重量%。
本发明所述的吸收促进剂并无特殊限制具体种类,可选自肉豆蔻酸异丙酯、乳酸薄荷酯、月桂氮卓酮、N-甲基吡咯烷酮、己二酸二乙酯、己二酸二异丙酯、油酸山梨醇酯、倍半油酸山梨醇酯、单硬酯酸聚乙二醇酯、聚氧亚烷基山梨糖醇酐脂肪酸酯等脂肪酸酯,薄荷醇、丙二醇、聚乙二醇等多元醇,聚氧乙烯氢化蓖麻油、聚山梨酯等表面活性剂,以及克罗米通等其中的一种或其中的几种任意比的组合,其中优选为薄荷醇、肉豆蔻酸异丙酯、克罗米通。以含药膏体层重量%计,其用量为0.1重量%-10重量%,优选为0.1重量%-5重量%。
本发明所述的保湿剂能抑制从膏体层中的水分的蒸发、防止膏体干燥。可选自乙二醇、丙二醇、丁二醇、甘油、聚乙二醇、液体石蜡、山梨醇溶液、尿素、吡咯烷酮羧酸盐等中的一种或其中的几种任意比的组合,其中优选为甘油、尿素、山梨醇溶液。以含药膏体层重量%计,其用量为1重量%-40重量%,优选1为重量%-20重量%。
本发明所述抗氧化剂可选自生育酚、抗坏血酸、柠檬酸、羟苯甲酮、二丁羟基甲苯等其中的一种或其中的几种任意比的组合,其中优选为抗坏血酸、二丁羟基甲苯。以含药膏体层重量%计,其用量为0.1重量%-10重量%,优选为0.1重量%-5重量%。
本发明所述pH调节剂可选自酒石酸、柠檬酸、磷酸、苹果酸或其盐等其中的一种或其中的几种任意比的组合,其中优选为酒石酸、酒石酸钠。以含药膏体层重量%计,其用量为0.1重量%-10重量%,优选为0.1-5重量%。
以含药膏体层重量%计,本发明所述的凝胶贴膏剂含水为25重量%-75重量%,优选为35重量%-65重量%。当含水量超过75重量%时,膏体层黏性降低,不利于贴敷,且容易如泥状残留于皮肤上;当含水量不足25重量%时,膏体容易变硬导致无法均一涂布,且容易对皮肤形成刺激。
本发明所述活性成分为洛索洛芬及其药用盐或药用酯,包括但不限于洛索洛芬、洛索洛芬钠、洛索洛芬二乙胺、洛索洛芬三乙胺、洛索洛芬单乙醇胺、洛索洛芬二乙醇胺、洛索洛芬三乙醇胺、洛索洛芬N-羟乙基吡咯烷、洛索洛芬N-羟乙基哌啶等其中的一种。
本发明所述的含药膏体层厚度范围可在100-2000μm之间,优选为500-1000μm之间。其支持体宜选用能支撑起胶体层的材料,可选自织布、无纺布、塑料膜、纸、人造丝等其中的一种或多种。
本发明所述的防黏膜可选由聚酯、聚氨酯、聚乙烯、聚丙烯等材料制成。
本发明中一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂的制备方法是按下述步骤进行的:将处方量的非甾体抗炎药及处方量的表面活性剂、抗氧化剂、增黏剂、吸收促进剂混合均匀,得到A溶液;将处方量的有机类保水树脂填充剂粉碎过筛后用纯化水分散均匀,得到B溶液;将处方量的交联剂及交联调节剂、依地酸二钠、pH调节剂在保湿剂中分散均匀,得到C溶液;将A溶液、B溶液和C溶液在搅拌釜内反复搅拌,直至膏体物成均一白色,测定pH值后,移入事先准备好支持体及防黏膜的涂布机内进行涂布、裁切,得到凝胶贴膏产品。
相对于以往采用无机类或矿物类填充剂的同类产品,本发明的产品具有更好的黏附性和透皮效果,透皮释放度更大,从而实现更好的疗效。
附图说明
图1表示实施例及比较例的凝胶贴膏剂的透皮释放度。
具体实施方式
以下示出具体实施例,对本发明进行具体说明,但本发明不受这些具体实施例的限定。
实施例1-3
将处方量的主药成分洛索洛芬钠及处方量的薄荷醇、抗坏血酸、聚乙烯醇、聚丙烯酸、己二酸二乙酯、聚山梨酯80、三乙酸甘油酯混合均匀,记为A溶液;将处方量的保水树脂类填充剂(粉碎过筛后)用纯化水分散均匀,记为B溶液;将处方量的干燥氢氧化铝凝胶、依地酸二钠、酒石酸、水硅酸镁在甘油中分散均匀,记为C溶液;将A、B、C溶液在搅拌釜内反复搅拌,直至膏体物成均一白色。测定pH值后,移入事先准备好无纺布及防黏膜的涂布机内进行涂布、裁切,得到凝胶贴膏产品。
实施例的处方及用量(含药膏体层重量%)如表1所示:
表1
比较例1-3
将处方量的主药成分洛索洛芬钠及处方量的薄荷醇、聚山梨酯80、抗坏血酸、聚乙烯醇、聚丙烯酸、己二酸二乙酯、三乙酸甘油酯混合均匀,记为A溶液;将处方量的无机类填充剂(粉碎过筛后)用纯化水分散均匀,记为B溶液;将处方量的干燥氢氧化铝凝胶、依地酸二钠、酒石酸、水硅酸镁在甘油中分散均匀,记为C溶液;将A、B、C溶液在搅拌釜内反复搅拌,直至膏体物成均一白色。测定pH值后,移入事先准备好无纺布及防黏膜的涂布机内进行涂布、裁切,得到凝胶贴膏产品。
比较例的处方及用量(膏体层重量%)如表2所示:
表2
试验方法1
将上述实施例及比较例分别剥去防黏膜,置于倾斜板上,按贴膏剂黏附力测定法第一法(《中国药典2020年版》第四部通则0952)测定各实施例及比较例的黏附力。
试验结果示于表3所示,由该结果(重复测定3次的平均值)可知,实施例1-3的黏附力优良,均能黏住24号至25号小球。而比较例1-3能黏住的小球号明显较低。(注:黏住的球号越大表示黏附力越强。)
表3
试验方法2
健康成年猪耳皮,按照标准热分离方法取得角质层,按体外透皮试验测定实施例1-3及比较例1-3的透皮释放度。将切割成合适大小的猪耳皮装载于Franz垂直扩散池内,取各样品切成直径20mm的圆形贴片,将该贴片贴附于猪皮角质层面。以pH为7.4的PBS缓冲溶液作为透皮介质,接收池体积为8ml,设定温度32℃,搅拌速度为100转每分钟。每次取样3ml,然后补加等温的空白接收液。每组样品平行6份,同时平行一份空白作为对照。照高效液相色谱法测定接收液中的洛索洛芬的浓度,最后计算出各试验贴片中洛索洛芬的透皮释放度。
试验结果示于图1,由该结果可知,与比较例1-3相比,实施例1-3的透皮释放度更大,具有良好的透皮效果,产品的疗效更好。
Claims (10)
1.一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂,由支持体、含药膏体层和防黏膜组成,其特征在于,其采用有机类保水树脂作为含药膏体层的填充剂。
2.根据权利要求1所述的外用凝胶贴膏剂,其特征在于,所述有机类保水树脂为淀粉接枝共聚物、聚丙烯酸类聚合物、聚乙烯醇类聚合物、纤维素接枝共聚物以及苯乙烯类共聚物其中的一种或其中的几种。
3.根据权利要求2所述的外用凝胶贴膏剂,其特征在于,所述淀粉接枝共聚物为淀粉接枝丙烯酸酯、淀粉接枝丙烯酰胺、淀粉接枝丙烯酸、淀粉接枝丙烯腈、淀粉黄原酸盐接枝丙烯酸盐中的一种或其中的几种。
4.根据权利要求2所述的外用凝胶贴膏剂,其特征在于,所述聚丙烯酸类聚合物为聚丙烯酸盐、聚丙烯酸盐加聚烯烃、丙烯腈纤维与丙烯酸盐复合物、醋酸乙烯丙烯酸酯等聚丙烯酸类聚合物中的一种或其中的几种。
5.根据权利要求2所述的外用凝胶贴膏剂,其特征在于,所述聚乙烯醇类聚合物为醋酸乙烯不饱和酸共聚物、醋酸乙烯丙烯酸酯共聚物、聚乙烯酸丙烯酰胺接枝共聚物、聚乙烯醇醋酐交联共聚物中的一种或其中的几种。
6.根据权利要求2所述的外用凝胶贴膏剂,其特征在于,所述纤维素接枝共聚物为纤维素接枝丙烯酸盐、纤维素接枝丙烯腈、纤维素黄原酸盐接枝丙烯酸盐、纤维素接枝丙烯酰胺中的一种或其中的几种;所述苯乙烯类共聚物为苯乙烯-异戊二烯-苯乙烯、苯乙烯-丁二烯-苯乙烯、氢化苯乙烯-丁二烯嵌段共聚物、苯乙烯-乙烯-丙烯-苯乙烯嵌段共聚物中的一种或其中的几种。
7.根据权利要求1所述的外用凝胶贴膏剂,其特征在于,所述有机类保水树脂的用量为1重量%-40重量%。
8.根据权利要求1所述的外用凝胶贴膏剂,其特征在于,所述有机类保水树脂的用量为1重量%-20重量%。
9.根据权利要求1所述的外用凝胶贴膏剂,其特征在于,含药膏体层还包括活性成分0.1重量%-10重量%,增粘剂1-40重量%,交联剂及交联调节剂0.1重量%-10重量%,吸收促进剂0.1重量%-10重量%,保湿剂1重量%-40重量%,抗氧化剂0.1重量%-10重量%,pH调节剂0.1重量%-10重量%,纯化水25重量%-75重量%;其中,所述活性成分为非甾体抗炎药,所述非甾体抗炎药是指洛索洛芬及其药用盐或酯,包括洛索洛芬、洛索洛芬钠、洛索洛芬二乙胺、洛索洛芬三乙胺、洛索洛芬单乙醇胺、洛索洛芬二乙醇胺、洛索洛芬三乙醇胺、洛索洛芬N-羟乙基吡咯烷、洛索洛芬N-羟乙基哌啶中的任意一种。
10.如权利要求1所述的外用凝胶贴膏剂的制备方法,其特征在于,所述制备方法是按下述步骤进行的:将处方量的非甾体抗炎药及处方量的表面活性剂、抗氧化剂、增黏剂、吸收促进剂混合均匀,得到A溶液;将处方量的有机类保水树脂填充剂粉碎过筛后用纯化水分散均匀,得到B溶液;将处方量的交联剂及交联调节剂、依地酸二钠、pH调节剂在保湿剂中分散均匀,得到C溶液;将A溶液、B溶液和C溶液在搅拌釜内反复搅拌,直至膏体物成均一白色,测定pH值后,移入事先准备好支持体及防黏膜的涂布机内进行涂布、裁切,得到凝胶贴膏产品。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011608898.2A CN113069437A (zh) | 2020-12-29 | 2020-12-29 | 一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011608898.2A CN113069437A (zh) | 2020-12-29 | 2020-12-29 | 一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂及其制备方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113069437A true CN113069437A (zh) | 2021-07-06 |
Family
ID=76609228
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011608898.2A Pending CN113069437A (zh) | 2020-12-29 | 2020-12-29 | 一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113069437A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115444837A (zh) * | 2022-10-13 | 2022-12-09 | 湖南九典制药股份有限公司 | 一种洛索洛芬经皮给药系统及其制备方法 |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS63104913A (ja) * | 1986-10-21 | 1988-05-10 | Teikoku Seiyaku Kk | 外用貼付剤 |
CN1231700A (zh) * | 1996-08-26 | 1999-10-13 | 三共株式会社 | 含有洛索丙芬的外用制剂 |
CN101896175A (zh) * | 2007-12-12 | 2010-11-24 | 帝国制药株式会社 | 含有环氧洛芬的水性贴剂 |
TW201605496A (zh) * | 2013-08-09 | 2016-02-16 | 帝國製藥股份有限公司 | 含有貝前列素(Beraprost)之貼附劑 |
CN106692110A (zh) * | 2015-08-19 | 2017-05-24 | 天津市山佳医药科技有限公司 | 一种芳基丙酸类非甾体抗炎药贴剂及其制备方法 |
WO2018017813A1 (en) * | 2016-07-20 | 2018-01-25 | Polich Nancy Josephine | High potency homeopathic gel formulation |
CN107951866A (zh) * | 2017-12-06 | 2018-04-24 | 北京茗泽中和药物研究有限公司 | 洛索洛芬钠贴剂 |
CN109843282A (zh) * | 2016-10-12 | 2019-06-04 | 帝国制药株式会社 | 水性贴剂 |
CN110946846A (zh) * | 2018-09-27 | 2020-04-03 | 湖南九典制药股份有限公司 | 一种不含透皮促渗剂的洛索洛芬钠凝胶膏基质及其制备方法 |
-
2020
- 2020-12-29 CN CN202011608898.2A patent/CN113069437A/zh active Pending
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS63104913A (ja) * | 1986-10-21 | 1988-05-10 | Teikoku Seiyaku Kk | 外用貼付剤 |
CN1231700A (zh) * | 1996-08-26 | 1999-10-13 | 三共株式会社 | 含有洛索丙芬的外用制剂 |
CN101658486A (zh) * | 1996-08-26 | 2010-03-03 | 第一三共株式会社 | 含有洛索丙芬的外用制剂 |
CN101896175A (zh) * | 2007-12-12 | 2010-11-24 | 帝国制药株式会社 | 含有环氧洛芬的水性贴剂 |
TW201605496A (zh) * | 2013-08-09 | 2016-02-16 | 帝國製藥股份有限公司 | 含有貝前列素(Beraprost)之貼附劑 |
CN106692110A (zh) * | 2015-08-19 | 2017-05-24 | 天津市山佳医药科技有限公司 | 一种芳基丙酸类非甾体抗炎药贴剂及其制备方法 |
WO2018017813A1 (en) * | 2016-07-20 | 2018-01-25 | Polich Nancy Josephine | High potency homeopathic gel formulation |
CN109843282A (zh) * | 2016-10-12 | 2019-06-04 | 帝国制药株式会社 | 水性贴剂 |
CN107951866A (zh) * | 2017-12-06 | 2018-04-24 | 北京茗泽中和药物研究有限公司 | 洛索洛芬钠贴剂 |
CN110946846A (zh) * | 2018-09-27 | 2020-04-03 | 湖南九典制药股份有限公司 | 一种不含透皮促渗剂的洛索洛芬钠凝胶膏基质及其制备方法 |
Non-Patent Citations (1)
Title |
---|
KHALID, IKRIMA等: "Cross-linked Sodium Alginate-g-poly(Acrylic Acid) Structure: A Potential Hydrogel Network for Controlled Delivery of Loxoprofen Sodium", ADVANCED IN POLYMER TECHNOLOGY, vol. 37, no. 4, 30 June 2018 (2018-06-30), pages 21747 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115444837A (zh) * | 2022-10-13 | 2022-12-09 | 湖南九典制药股份有限公司 | 一种洛索洛芬经皮给药系统及其制备方法 |
CN115444837B (zh) * | 2022-10-13 | 2023-08-22 | 湖南九典制药股份有限公司 | 一种洛索洛芬经皮给药系统及其制备方法 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10596126B2 (en) | Transdermal therapeutic system comprising active ingredient particles and having increased active ingredient flux | |
FI110161B (fi) | Menetelmä joustavan, biologisesti tarttuvan koostumuksen valmistamiseksi paikallista antomuotoa varten | |
US4695465A (en) | Soft patch | |
US5332576A (en) | Compositions and methods for topical administration of pharmaceutically active agents | |
JP2001508037A (ja) | 粘膜表面への、薬学的化合物の送達に適する薬学的キャリアデバイス | |
JPH0684304B2 (ja) | チモロール用経皮的系 | |
WO2002032431A1 (fr) | Compositions pour preparations externes | |
JPH06104624B2 (ja) | 経皮吸収剤 | |
AU2003229563A1 (en) | Hybrid system for solubilizing pharmaceutically active substances in polymer matrices | |
KR101727347B1 (ko) | 디클로페낙 나트륨 함유 수성 패치 | |
JPH03275619A (ja) | 外用剤組成物 | |
CN110787150A (zh) | 一种含有氟比洛芬的皮肤外用制剂 | |
JPS58213709A (ja) | 歯肉粘膜用貼付剤 | |
US6685959B1 (en) | Pharmaceutical compositions comprising 2-isoxazoles-8-aminotetralin derivatives | |
JPWO2009051217A1 (ja) | フェンタニル含有経皮吸収製剤 | |
CN113069437A (zh) | 一种含有洛索洛芬及其药用盐的外用凝胶贴膏剂及其制备方法 | |
WO2000064435A1 (fr) | Preparations a base d'oxybutynine destinees a etre absorbees par voie percutanee | |
CN109771395B (zh) | 一种含有槲皮素的口腔黏膜剂及其制备方法 | |
CN1694699A (zh) | 含有3-甲基-1-苯基-2-吡唑啉-5-酮的透皮吸收制剂 | |
CN111067905A (zh) | 噻吗洛尔或其盐的组合物、其水凝胶贴膏剂以及治疗血管瘤的用途 | |
JPH1149670A (ja) | 局所麻酔用経皮吸収型製剤 | |
CN113018278A (zh) | 一种含有非甾体抗炎药的外用凝胶贴膏剂及其制备方法 | |
JPH09143061A (ja) | 鎮痛剤用経皮吸収製剤 | |
CN107028915B (zh) | 含有布比卡因或其药用盐的皮肤外用制剂 | |
CN108210929A (zh) | 一种含有依托考昔的药物组合物及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |