JPH0436134B2 - - Google Patents
Info
- Publication number
- JPH0436134B2 JPH0436134B2 JP59132473A JP13247384A JPH0436134B2 JP H0436134 B2 JPH0436134 B2 JP H0436134B2 JP 59132473 A JP59132473 A JP 59132473A JP 13247384 A JP13247384 A JP 13247384A JP H0436134 B2 JPH0436134 B2 JP H0436134B2
- Authority
- JP
- Japan
- Prior art keywords
- indomethacin
- base material
- menthol
- camphor
- solid solution
- 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.)
- Expired - Lifetime
Links
- 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 claims description 106
- 229960000905 indomethacin Drugs 0.000 claims description 53
- LVYLCBNXHHHPSB-UHFFFAOYSA-N 2-hydroxyethyl salicylate Chemical compound OCCOC(=O)C1=CC=CC=C1O LVYLCBNXHHHPSB-UHFFFAOYSA-N 0.000 claims description 52
- 239000002585 base Substances 0.000 claims description 40
- 239000000463 material Substances 0.000 claims description 39
- 229960002389 glycol salicylate Drugs 0.000 claims description 26
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 24
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 claims description 24
- 241000723346 Cinnamomum camphora Species 0.000 claims description 24
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 24
- 229960000846 camphor Drugs 0.000 claims description 24
- 229930008380 camphor Natural products 0.000 claims description 24
- 229940041616 menthol Drugs 0.000 claims description 24
- 239000006104 solid solution Substances 0.000 claims description 22
- 229920002125 Sokalan® Polymers 0.000 claims description 15
- 239000000017 hydrogel Substances 0.000 claims description 15
- 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 description 14
- 229920000058 polyacrylate Polymers 0.000 claims description 14
- -1 alginate alkali metal salt Chemical class 0.000 claims description 13
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 13
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 13
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 12
- 239000004584 polyacrylic acid Substances 0.000 claims description 12
- 229910021645 metal ion Inorganic materials 0.000 claims description 11
- 229940072056 alginate Drugs 0.000 claims description 10
- 229920000615 alginic acid Polymers 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 9
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 230000000052 comparative effect Effects 0.000 description 18
- 206010030113 Oedema Diseases 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 11
- 230000003110 anti-inflammatory effect Effects 0.000 description 10
- 230000001760 anti-analgesic effect Effects 0.000 description 9
- 230000001629 suppression Effects 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 108010010803 Gelatin Proteins 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 239000008273 gelatin Substances 0.000 description 8
- 229920000159 gelatin Polymers 0.000 description 8
- 235000019322 gelatine Nutrition 0.000 description 8
- 235000011852 gelatine desserts Nutrition 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 235000010443 alginic acid Nutrition 0.000 description 6
- 235000010418 carrageenan Nutrition 0.000 description 6
- 229920001525 carrageenan Polymers 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
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 210000002683 foot Anatomy 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 235000002568 Capsicum frutescens Nutrition 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 239000000679 carrageenan Substances 0.000 description 3
- 229940113118 carrageenan Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 210000003141 lower extremity Anatomy 0.000 description 3
- 239000011505 plaster Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-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
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 2
- 208000018522 Gastrointestinal disease Diseases 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 241001247145 Sebastes goodei Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000004132 cross linking Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 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 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 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 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- CRBBOOXGHMTWOC-NPDDRXJXSA-N 1,4-Anhydro-6-O-dodecanoyl-2,3-bis-O-(2-hydroxyethyl)-D-glucitol Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](OCCO)[C@H]1OCCO CRBBOOXGHMTWOC-NPDDRXJXSA-N 0.000 description 1
- SPCKHVPPRJWQRZ-UHFFFAOYSA-N 2-benzhydryloxy-n,n-dimethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 SPCKHVPPRJWQRZ-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- WZUKKIPWIPZMAS-UHFFFAOYSA-K Ammonium alum Chemical compound [NH4+].O.O.O.O.O.O.O.O.O.O.O.O.[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O WZUKKIPWIPZMAS-UHFFFAOYSA-K 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 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 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 229920002085 Dialdehyde starch Polymers 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical group CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 206010030124 Oedema peripheral Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
- 208000010040 Sprains and Strains Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 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 1
- 239000005844 Thymol Substances 0.000 description 1
- UKNGDQSYPNBJAO-UHFFFAOYSA-N Tiaramide hydrochloride Chemical compound Cl.C1CN(CCO)CCN1C(=O)CN1C(=O)SC2=CC=C(Cl)C=C21 UKNGDQSYPNBJAO-UHFFFAOYSA-N 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- HDYRYUINDGQKMC-UHFFFAOYSA-M acetyloxyaluminum;dihydrate Chemical compound O.O.CC(=O)O[Al] HDYRYUINDGQKMC-UHFFFAOYSA-M 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 235000011124 aluminium ammonium sulphate Nutrition 0.000 description 1
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 1
- 235000011126 aluminium potassium sulphate Nutrition 0.000 description 1
- DIZPMCHEQGEION-UHFFFAOYSA-H aluminium sulfate (anhydrous) Chemical compound [Al+3].[Al+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O DIZPMCHEQGEION-UHFFFAOYSA-H 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940009827 aluminum acetate Drugs 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- LCPUDZUWZDSKMX-UHFFFAOYSA-K azane;hydrogen sulfate;iron(3+);sulfate;dodecahydrate Chemical compound [NH4+].O.O.O.O.O.O.O.O.O.O.O.O.[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O LCPUDZUWZDSKMX-UHFFFAOYSA-K 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 235000015278 beef Nutrition 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
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- 239000003431 cross linking reagent Substances 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 239000010642 eucalyptus oil Substances 0.000 description 1
- 229940044949 eucalyptus oil Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229960002089 ferrous chloride Drugs 0.000 description 1
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000003349 gelling agent Substances 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
- 210000000548 hind-foot Anatomy 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- NMCUIPGRVMDVDB-UHFFFAOYSA-L iron dichloride Chemical compound Cl[Fe]Cl NMCUIPGRVMDVDB-UHFFFAOYSA-L 0.000 description 1
- RUTXIHLAWFEWGM-UHFFFAOYSA-H iron(3+) sulfate Chemical compound [Fe+3].[Fe+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O RUTXIHLAWFEWGM-UHFFFAOYSA-H 0.000 description 1
- 229910000360 iron(III) sulfate Inorganic materials 0.000 description 1
- NCNCGGDMXMBVIA-UHFFFAOYSA-L iron(ii) hydroxide Chemical compound [OH-].[OH-].[Fe+2] NCNCGGDMXMBVIA-UHFFFAOYSA-L 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004898 kneading Methods 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 229910052901 montmorillonite Inorganic materials 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000000123 paper Substances 0.000 description 1
- 229940116257 pepper extract Drugs 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 229920001083 polybutene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229940050271 potassium alum Drugs 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 229940045920 sodium pyrrolidone carboxylate Drugs 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- HYRLWUFWDYFEES-UHFFFAOYSA-M sodium;2-oxopyrrolidine-1-carboxylate Chemical compound [Na+].[O-]C(=O)N1CCCC1=O HYRLWUFWDYFEES-UHFFFAOYSA-M 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 229940098465 tincture Drugs 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000002759 woven fabric Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、多価金属イオン架橋型含水ゲル基材
にインドメタシンを配合した水性パツプ剤に関
し、更に詳述すると、インドメタシンの経皮吸収
率が高く、優れた消炎鎮痛作用を有すると共に、
皮膚に対する安全性が高い水性パツプ剤に関す
る。
従来より、インドメタシンは整形外科領域で慢
性関節リウマチ、変形性関節炎症等の治療に使用
され、優れた効果が認められている。しかし、一
方では内服投与した場合に消化器障害等の副作用
が生じるという点が問題視されていた。
この点を解決する手段として、近年インドメタ
シンを配合した液剤、軟膏剤、パツプ剤等の各種
外用剤が開発され、インドメタシンを直接皮膚に
適用することが可能になつた。
しかしながら、インドメタシンは水不溶性であ
るため、単にその粉末を外用基材に配合したのみ
では充分に経皮吸収させることができず、従つて
インドメタシンを少なくとも一部溶解した状態で
基材に配合する必要があるが、溶媒として従来イ
ンドメタシンの良溶媒として知られている低級ア
ルコール類を用いた場合、低級アルコール類は水
と容易に混和するため、基材中におけるインドメ
タシンの溶解度が極端に低下するという問題があ
る。しかも、低級アルコール類を溶媒として薬理
効果が期待できる量のインドメタシンを基材に配
合しようとすると、低級アルコール類を高濃度で
基材に配合しなければならず、皮膚への安全性の
点で好ましくない。
本発明者らは、上記事情に鑑み、外用剤にイン
ドメタシンを溶解状態で安定に配合し、インドメ
タシンの経皮吸収率を高めることにつき種々研究
を行なつた結果、ポリアクリル酸及びポリアクリ
ル酸塩を含有し、更にカルボキシメチルセルロー
スナトリウム及び／又はアルギン酸アルカリ金属
塩を含有する多価金属イオン架橋型含水ゲル基材
にインドメタシンと共にメントールとカンフルと
の固溶体及び／又はサリチル酸グリコールを配合
することにより、上記目的が効果的に達成される
ことを知見した。
即ち、本発明者らは、インドメタシンを配合す
る基材としてポリアクリル酸及びポリアクリル酸
塩を含有し、更にカルボキシメチルセルロースナ
トリウム及び／又はアルギン酸アルカリ金属塩を
含有する多価金属イオン架橋型含水ゲル基材を選
択し、インドメタシン含有外用剤を上記基材の水
性パツプ剤とし、インドメタシンと共にメントー
ルとカンフルとの固溶体及び／又はサリチル酸グ
ルコールを外用基材に配合した場合、これがイン
ドメタシンの良溶媒となり、しかもメントールと
カンフルとの固溶体やサリチル酸グリコールは容
易に水と混和しないため、インドメタシンが溶解
した状態で配合され、インドメタシンの経皮吸収
性が高められると共に、上記基材と、インドメタ
シン並びにメントールとカンフルとの固溶体及
び／又はサリチル酸グリコールが相乗的に作用し
て高い消炎鎮痛作用を有する外用剤が得られ、し
かもメントールとカンフルとの固溶体やサリチル
酸グリコールを用いることにより皮膚に対する安
全性に問題がない外用剤が得られることを知見し
た。
更に詳述すると、後述する第４表の結果から明
らかなように、カルボンキシビニルポリマーをア
ミンでゲル化したゲルやゼラチンとカルボキシメ
チルセルロースナトリウムを含むゼラチン基材か
らなるパツプ剤、更にクリームの剤型に調製した
ものと比較し、ポリアクリル酸及びポリアクリル
酸塩を含有し、かつカルボキシメチルセルロース
ナトリウム及び／又はアルギン酸アルカリ金属塩
を含有する多価金属イオン架橋型含水ゲル基材を
使用すると、同量のインドメタシン及びメントー
ルとカンフルとの固溶体又はサリチル酸グリコー
ルを配合した場合において、より優れた浮腫抑制
率を与えることを見い出したものである。
本発明によれば、ポリアクリル酸及びポリアク
リル酸塩を含有し、更にカルボキシメチルセルロ
ースナトリウム及び／又はアルギン酸アルカリ金
属塩を含有する多価金属イオン架橋型含水ゲル基
材の水性パツプ剤に対しインドメタシンがメント
ールとカンフルとの固溶体及び／又はサリチル酸
グリコールと共に配合されていることにより、イ
ンドメタシンの経皮吸収率が高く、その薬理作用
を最大限に引き出すことができるものである。し
かも、本発明によれば、内服投与した場合には消
化器障害等の副作用が生じるインドメタシンを直
接患部に効率的に経皮投与することができ、この
点でも治療の安全性に寄与するものである。
以下、本発明につき更に詳しく説明する。
本発明に係る水性パツプ剤は、ポリアクリル酸
及びポリアクリル酸塩を含有し、更にカルボキシ
メチルセルロースナトリウム及び／又はアルギン
酸アルカリ金属塩を含有する多価金属イオン架橋
型含水ゲル基材にインドメタシンを配合すると共
に、メントールとカンフルとの固溶体及び／又は
サリチル酸グリコールを配合してなるもので、こ
れによりインドメタシンが溶解状態で安定に配合
されると共に、優れた消炎鎮痛作用を与えるもの
である。
この場合、本発明は、上述したように、ポリア
クリル酸及びポリアクリル酸塩を含有し、更にカ
ルボキシメチルセルロースナトリウム及び／又は
アルギン酸アルカリ金属塩を含有する多価金属イ
オン架橋型含水ゲル基材（非ゼラチン系基材）を
使用するもので、上記組成の含水ゲル基材は粘着
力が強く、含水率が高く、保型性に優れているた
め、この含水ゲル基材を用いることにより、これ
に有効成分を配合した場合この有効成分が皮膚に
効率的に吸収される。
なお、上記組成の含水ゲル基材は、ポリアクリ
ル酸とポリアクリル酸塩との配合比率を変えるこ
とにより、任意のPHを有する基材を得ることがで
きるものであるが、この場合ポリアクリル酸とポ
リアクリル酸塩の配合比（重量比）は１：９〜
８：２とすることが好ましく、ポリアクリル酸重
量がポリアクリル酸−ポリアクリル酸塩重量の1/
１０より少ないと肌への十分な粘着力が得られない
場合があり、またポリアクリル酸−ポリアクリル
酸塩重量の8/10より多いと十分な増粘が行われ
ず、膏体がダレる場合が生じる。
更に、上記成分からなる含水ゲル基材を多価金
属塩により金属架橋する場合、多価金属塩として
は塩化カルシウム、塩化マグネシウム、塩化アル
ミニウム、カリ明バン、アンモニウム明バン、鉄
明バン、硫酸アルミニウム、硫酸第２鉄、硫酸マ
グネシウム、EDAT−カルシウム、EDAT−ア
ルミニウム、EDAT−マグネシウム、塩化第１
錫等の可溶性塩、水酸化カルシウム、水酸化第２
鉄、水酸化アルミニウム、炭酸カルシウム、炭酸
マグネシウム、リン酸カルシウム、ステアリン酸
マグネシウム、ステアリン酸アルミニウム、クエ
ン酸カルシウム、硫酸バリウム、水酸化バリウ
ム、アルミニウムアラントイネート、酢酸アルミ
ニウム、アルミニウムグリシナール、水酸化第１
錫、α−錫酸等の微溶性又は難溶性塩などから選
ばれる１種又は２種以上、更に架橋反応の速度調
整剤としてEDAT−２ナトリウム、クエン酸、
酒石酸、尿素、アンモニア等の金属イオンに対し
てキレートもしくは配位能を持つ有機酸、有機酸
塩、有機塩基などを配合し得る。
なお、上記水溶性高分子物質の配合量は総計で
通常基材全体の１〜15％（重量％、以下同じ）と
することが好ましく、１％より少ないと膏体ペー
ストとして十分な粘度が得られない場合があり、
15％より多いと粘度が高くなり作業性が低下する
ことがある。また、基材には、カオリン、ベント
ナイト、モンモリロナイト、酸化チタン、酸化亜
鉛、水酸化アルミニウム、無水ケイ酸（例えばア
エロジル）等の１種又は２種以上の無機粉体
（配合量通常０〜10％。上限に特に制限はなく、
含水率とのバランスによつて決定される。）、プロ
ピレングリコール、グリセリン、ソルビトール、
ポリエチレングリコール、ピロリドンカルボン酸
ソーダ、乳酸ナトリウム等の１種又は２種以上の
保湿剤（配合量通常０〜20％。上限に特に制限は
なく、含水率とのバランスによつて決定される。）
及び水を適宜割合で混合したものなどを配合する
ことができる。
なお、本発明においては、インドメタシンの
pKaが4.5であることから、基材としてPHが４〜
6.5の弱酸性のものを用いることが好ましく、こ
れにより非解離型のインドメタシン分子の割合が
増大するため、インドメタシンの経皮吸収率が高
まると共に、保存安定性が向上する。
本発明においては、上述した基材にインドメタ
シンと共にメントールとカンフルとの固溶体及
び／又はサリチル酸グリコールを配合するもので
ある。
ここで、メントールとカンフルとの固溶体とし
ては、メントールとカンフルとの配合比が10：１
〜１：10、特に２：１〜１：２（重量比）である
ものを好適に使用し得る。
また、インドメタシンの配合量は基材全体の
0.1〜５％、特に0.3〜２％とすることが好まし
く、メントールとカンフルとの固溶体及び／又は
サリチル酸グリコールの配合量はインドメタシン
の１重量倍以上、特に５重量倍以上とすることが
好ましく、通常0.5〜30％の範囲における適宜量
とすることが好適である。
なお、インドメタシンの基材への配合方法は限
定されないが、予じめメントールとカンフルとの
固溶体やサリチル酸グリコールに溶解させ、これ
を基材に配合する方法が好適に採用し得る。
本発明水性パイプ剤には、上記インドメタシ
ン、メントール、カンフル、サリチル酸グリコー
ルのほか、所望によりサリチル酸メチル、フルフ
エナム酸とその誘導体、メフエナム酸とその誘導
体、ジクロフエナツクナトリウム、アスピリン、
イブプロフエン、スリンダク、ナプロキセン、ピ
ロキシカム、塩酸チアラミド、フエンブフエン、
ハツカ油、ユーカリ油、ビタミンＥ、ジフェンヒ
ドラミン、マレイン酸クロルフエニラミン、チモ
ール、唐辛子エキス、唐辛子末、唐辛子チンキ、
カプサイシン、ノニル酸ワニルアミド等の有効成
分の１種又は２種以上を配合し得る（配合量通常
０〜20％）。
更に、本発明においては、上記成分に加えて必
要に応じ膏体物性（柔軟性、粘着性、保型性等）
の調整剤としてポリブテン、ラテツクス、酢酸ビ
ニルエマルシヨン、アクリル樹脂エマルシヨン等
の高分子物質、架橋ゲル化剤として種々の多価金
属塩、ジアルデヒドデンプン等の有機架橋化剤、
有効成分の安定配合剤としてラノリン、流動パラ
フイン、植物油、豚脂、牛脂、高級アルコール、
高級脂肪酸、活性剤等の適宜成分を配合すること
ができる。
本発明の外用剤は常法に従つて製造し得、例え
ば水性パツプ剤は、上記各成分をよく練合してペ
ースト状に調製し、これを紙、織布、不織布、プ
ラスチツクフイルム等の支持体（バツキング）に
塗布し、必要によりポリエチレンフイルム等のフ
エイシングを被覆することにより得られるもので
ある。
而して、本発明に係る水性パツプ剤は、ポリア
クリル酸及びポリアクリル酸塩を含有し、更にカ
ルボキシメチルセルロースナトリウム及び／又は
アルギン酸アルカリ金属塩を含有する多価金属イ
オン架橋型含水ゲル基材にインドメタシンを配合
すると共に、メントールとカンフルとの固溶体及
び／又はサリチル酸グリコールを配合したことに
より、インドメタシンが溶解状態で安定に配合さ
れ、インドメタシンの経皮吸収率が高いと共に、
上記基材におけるインドメタシン並びにメントー
ルとカンフルとの固溶体及び／又はサリチル酸グ
リコールの相乗作用により優れた消炎鎮痛作用を
示し、しかも皮膚に対する安全性が高いものであ
り、打撲、捻挫、腰痛、肩こり、筋肉痛、関節
炎、リウマチ等の治療用に好適に使用されるもの
である。
次に実施例及び比較例を示し、本発明を具体的
に説明する。
〔実施例１〜９、比較例１〜13〕
第１〜３表に示す組成の水性パツプ基材を常法
に従つて調製し、これをリント布上に均一厚さに
展延、塗布し、更にその表面をポリエチレンフイ
ルムでフエイシングして実施例１〜９、比較例１
〜13のパツプ剤をそれぞれ得た。この場合、メン
トール及びカンフルはこれらの固溶体として配合
した。また、インドメタシンはサリチル酸グリコ
ール又はメントールとカンフルとの固溶体に予じ
め溶解しておいた。なお、水性パツプ基材のPHは
いずれも4.6〜4.8の範囲内であつた。
The present invention relates to an aqueous poultice containing indomethacin in a polyvalent metal ion crosslinked hydrogel base material, and more specifically, indomethacin has a high percutaneous absorption rate and has excellent anti-inflammatory and analgesic effects.
This invention relates to an aqueous poultice that is highly safe for the skin. Indomethacin has traditionally been used in the field of orthopedics to treat rheumatoid arthritis, osteoarthritis, etc., and its excellent effects have been recognized. However, on the other hand, it has been viewed as a problem that side effects such as gastrointestinal disorders occur when administered internally. As a means to solve this problem, various external preparations such as liquid preparations, ointments, and poultices containing indomethacin have been developed in recent years, and it has become possible to apply indomethacin directly to the skin. However, since indomethacin is water-insoluble, it is not possible to achieve sufficient transdermal absorption by simply blending its powder into a topical base material.Therefore, it is necessary to blend indomethacin into the base material in a state in which at least a portion of it is dissolved. However, when lower alcohols, which are conventionally known as good solvents for indomethacin, are used as a solvent, there is a problem that the solubility of indomethacin in the base material is extremely reduced because lower alcohols are easily miscible with water. There is. Moreover, if we try to blend indomethacin into a base material in an amount that can be expected to have a pharmacological effect using lower alcohols as a solvent, the lower alcohols must be blended into the base material at a high concentration, which poses safety concerns for the skin. Undesirable. In view of the above circumstances, the present inventors have conducted various studies on stably blending indomethacin in a dissolved state into external preparations and increasing the transdermal absorption rate of indomethacin. The above purpose can be achieved by blending indomethacin with a solid solution of menthol and camphor and/or glycol salicylate into a polyvalent metal ion crosslinked hydrogel base material containing sodium carboxymethyl cellulose and/or alkali metal alginate. It was found that this can be effectively achieved. That is, the present inventors have developed a polyvalent metal ion-crosslinked hydrogel group containing polyacrylic acid and polyacrylate as a base material in which indomethacin is blended, and further containing sodium carboxymethyl cellulose and/or alkali metal alginate. If a topical preparation containing indomethacin is selected as a water-based poultice with the above-mentioned base material, and a solid solution of menthol and camphor and/or glycol salicylate is blended with indomethacin in the topical base material, this will become a good solvent for indomethacin, and it will also act as a good solvent for indomethacin. Since a solid solution of menthol and camphor and glycol salicylate are not easily miscible with water, indomethacin is blended in a dissolved state, and the transdermal absorption of indomethacin is enhanced. And/or glycol salicylate acts synergistically to obtain a topical preparation that has high anti-inflammatory and analgesic effects, and by using a solid solution of menthol and camphor or glycol salicylate, a topical preparation that has no safety problems on the skin can be obtained. I found out that it can be done. More specifically, as is clear from the results in Table 4 below, the formulations include gels made of carboxyvinyl polymer gelled with amines, poultices made of gelatin base material containing gelatin and sodium carboxymethylcellulose, and cream formulations. Compared to the one prepared in It has been found that when indomethacin and a solid solution of menthol and camphor or glycol salicylate are combined, a superior edema suppression rate can be obtained. According to the present invention, indomethacin is applied to an aqueous poultice of a polyvalent metal ion crosslinked hydrogel base material containing polyacrylic acid and polyacrylate, and further containing sodium carboxymethyl cellulose and/or alginate alkali metal salt. By being formulated with a solid solution of menthol and camphor and/or glycol salicylate, indomethacin has a high transdermal absorption rate and can maximize its pharmacological action. Moreover, according to the present invention, indomethacin, which causes side effects such as gastrointestinal disorders when administered internally, can be efficiently administered transdermally directly to the affected area, which also contributes to the safety of the treatment. be. The present invention will be explained in more detail below. The aqueous poultice of the present invention contains indomethacin in a polyvalent metal ion crosslinked hydrogel base material containing polyacrylic acid and polyacrylate, and further containing sodium carboxymethyl cellulose and/or alkali metal alginate. In addition, it contains a solid solution of menthol and camphor and/or glycol salicylate, which allows indomethacin to be stably blended in a dissolved state and provides excellent anti-inflammatory and analgesic effects. In this case, as described above, the present invention provides a polyvalent metal ion crosslinked hydrogel base material (non-containing polyvalent metal ion-crosslinked hydrogel base material) containing polyacrylic acid and polyacrylate salt, and further containing sodium carboxymethyl cellulose and/or alginate alkali metal salt. The hydrogel base material with the above composition has strong adhesive strength, high water content, and excellent shape retention. When an active ingredient is blended, the active ingredient is efficiently absorbed into the skin. Note that the hydrogel base material with the above composition can have a desired pH by changing the blending ratio of polyacrylic acid and polyacrylate; however, in this case, polyacrylic acid The blending ratio (weight ratio) of and polyacrylate is 1:9 ~
The ratio is preferably 8:2, with the weight of polyacrylic acid being 1/1/2 of the weight of polyacrylic acid-polyacrylate.
If it is less than 10, sufficient adhesion to the skin may not be obtained, and if it is more than 8/10 of the weight of polyacrylic acid-polyacrylate, sufficient thickening may not occur and the paste may sag. occurs. Furthermore, when a hydrogel base material consisting of the above components is metal-crosslinked with a polyvalent metal salt, examples of the polyvalent metal salt include calcium chloride, magnesium chloride, aluminum chloride, potassium alum, ammonium alum, iron alum, and aluminum sulfate. , ferric sulfate, magnesium sulfate, EDAT-calcium, EDAT-aluminum, EDAT-magnesium, ferrous chloride
Soluble salts such as tin, calcium hydroxide, dihydroxide
Iron, aluminum hydroxide, calcium carbonate, magnesium carbonate, calcium phosphate, magnesium stearate, aluminum stearate, calcium citrate, barium sulfate, barium hydroxide, aluminum allantoinate, aluminum acetate, aluminum glycinal, primary hydroxide
One or more salts selected from slightly soluble or poorly soluble salts such as tin and α-stannic acid, as well as EDAT-disodium, citric acid, and crosslinking reaction rate regulators.
Organic acids, organic acid salts, organic bases, etc. that have the ability to chelate or coordinate metal ions such as tartaric acid, urea, and ammonia may be blended. The total amount of the above-mentioned water-soluble polymeric substances is usually preferably 1 to 15% (by weight, the same hereinafter) of the entire base material, and if it is less than 1%, sufficient viscosity as a paste may not be obtained. may not be possible,
If it exceeds 15%, the viscosity may increase and workability may decrease. The base material also contains one or more inorganic powders (compounding amount usually 0 to 10%) such as kaolin, bentonite, montmorillonite, titanium oxide, zinc oxide, aluminum hydroxide, and silicic anhydride (e.g. Aerosil). .There is no particular limit on the upper limit.
Determined by the balance with moisture content. ), propylene glycol, glycerin, sorbitol,
One or more types of humectants such as polyethylene glycol, sodium pyrrolidone carboxylate, and sodium lactate (compounding amount is usually 0 to 20%. There is no particular upper limit, and it is determined by the balance with the water content.)
and water in appropriate proportions may be blended. In addition, in the present invention, indomethacin
Since the pKa is 4.5, the pH is 4 to 4 as a base material.
It is preferable to use a weakly acidic acid of 6.5, which increases the proportion of non-dissociated indomethacin molecules, thereby increasing the transdermal absorption rate of indomethacin and improving its storage stability. In the present invention, a solid solution of menthol and camphor and/or glycol salicylate is blended with indomethacin in the above-mentioned base material. Here, as a solid solution of menthol and camphor, the blending ratio of menthol and camphor is 10:1.
-1:10, especially 2:1 - 1:2 (weight ratio) can be suitably used. In addition, the amount of indomethacin added is
It is preferably 0.1 to 5%, particularly 0.3 to 2%, and the amount of the solid solution of menthol and camphor and/or glycol salicylate is preferably 1 times or more, especially 5 times or more by weight of indomethacin, and usually An appropriate amount in the range of 0.5 to 30% is suitable. Note that the method for blending indomethacin into the base material is not limited, but a method of dissolving indomethacin in advance in a solid solution of menthol and camphor or glycol salicylate and blending this into the base material can be suitably employed. In addition to the above-mentioned indomethacin, menthol, camphor, and glycol salicylate, the aqueous pipe preparation of the present invention includes, if desired, methyl salicylate, flufenamic acid and its derivatives, mefenamic acid and its derivatives, diclofenac sodium, aspirin,
ibuprofen, sulindac, naproxen, piroxicam, thiaramide hydrochloride, fenbufuene,
Peppermint oil, eucalyptus oil, vitamin E, diphenhydramine, chlorpheniramine maleate, thymol, chili pepper extract, chili powder, chili pepper tincture,
One or more active ingredients such as capsaicin and nonylic acid vanylamide may be blended (the blending amount is usually 0 to 20%). Furthermore, in the present invention, in addition to the above components, physical properties of the paste (flexibility, adhesiveness, shape retention, etc.) may be added as necessary.
Polymer substances such as polybutene, latex, vinyl acetate emulsion, acrylic resin emulsion, etc. as regulators, various polyvalent metal salts as crosslinking gelling agents, organic crosslinking agents such as dialdehyde starch,
Stabilizing agents for active ingredients include lanolin, liquid paraffin, vegetable oil, lard, beef tallow, higher alcohol,
Appropriate components such as higher fatty acids and activators can be blended. The external preparation of the present invention can be manufactured according to a conventional method. For example, an aqueous poultice is prepared by thoroughly kneading the above-mentioned components to form a paste, and then applying the paste to a support such as paper, woven fabric, non-woven fabric, plastic film, etc. It is obtained by applying it to the body (backing) and, if necessary, covering it with a facing such as polyethylene film. Therefore, the aqueous poultice according to the present invention contains a polyvalent metal ion crosslinked hydrogel base material containing polyacrylic acid and polyacrylate, and further containing sodium carboxymethyl cellulose and/or alkali metal alginate. By blending indomethacin with a solid solution of menthol and camphor and/or glycol salicylate, indomethacin is stably blended in a dissolved state, and the transdermal absorption rate of indomethacin is high.
It exhibits excellent anti-inflammatory and analgesic effects due to the synergistic effect of indomethacin, a solid solution of menthol and camphor, and/or glycol salicylate in the above-mentioned base material, and is highly safe for the skin, preventing bruises, sprains, lower back pain, stiff shoulders, and muscle pain. , arthritis, rheumatism and the like. Next, examples and comparative examples will be shown to specifically explain the present invention. [Examples 1 to 9, Comparative Examples 1 to 13] Aqueous pad base materials having the compositions shown in Tables 1 to 3 were prepared according to a conventional method, and spread and applied to a uniform thickness on a lint cloth. Further, the surface was faced with a polyethylene film to prepare Examples 1 to 9 and Comparative Example 1.
~13 poultices were obtained each. In this case, menthol and camphor were blended as a solid solution thereof. Moreover, indomethacin was previously dissolved in glycol salicylate or a solid solution of menthol and camphor. In addition, the pH of all aqueous pad base materials was within the range of 4.6 to 4.8.
【表】【table】
【表】【table】
【表】【table】
【表】【table】
【表】
更に、比較のため、下記処方のゲル、クリー
ム、パツプ剤を調製した。
〔比較例 14〕ゲル
カルボキシビニルポリマー 1.5％
プロピレングリコール 10.0％
トリエタノールアミン 1.0％
インドメタシン 0.5％
サリチル酸グリコール 2.5％
エタノール 35.0％水 残量
計 100.0％
〔比較例 15〕クリーム
セタノール 7.0％
ステアリン酸 3.0
アジピン酸ジイソプロピル 5.0
流動パラフイン 5.0
グリセリン 10.0
POE（20）ソルビタンモノステアレート 4.0
ソルビタンモノステアレート 1.2
パラオキシ安息香酸プロピル 0.05
パラオキシ安息香酸メチル 0.05
インドメタシン 0.5
サリチル酸グリコール 2.5水 残量
計 100.0％
〔比較例16〕パツプ剤
ゼラチン 5.0％
カルボキシメチルセルロースナトリウム 6.0
グリセリン 35.0
ヒマシ油 1.0
POE（20）ソルビタンモノオレエート 1.0
カオリン 10.0
硫酸アルミニウムカリウム 0.02
クエン酸 0.01
インドメタシン 0.5
サリチル酸グリコール 2.5水 残量
計 100.0％
次に、上記実施例１〜９、比較例１〜16の外用
剤を用いて下記実験１，２を行なつた。
実験 １
下記カラゲニン足浮腫抑制試験により実施例１
〜９、比較例１〜16の外用剤が有する抗炎症作用
を調べた。
カラゲニン足浮腫抑制試験
体重140〜160ｇのウイスター系雄性ラツトを一
群10匹として用い、各ラツトの右後肢の足容積を
ボリユームデイフアレンシヤルメーター（Vgo
Basile社製）で測定した後、１％カラゲニン懸濁
液（起炎剤）0.1mlを同足蹠皮下にそれぞれ注射
する。パツプ剤は起炎剤注射４時間前に右後肢に
貼付しておき、注射後の右後肢の足容積を上記メ
ータで測定し、注射前後の足容積の差から下記式
により浮腫率と各パツプ剤の浮腫抑制率を求めた
（比較例14のゲル、比較例15のクリームはそれぞ
れその500mgを右後肢に塗布した）。なお、試験中
に貼付したパツプ剤をラツトが咬んだり舐めたり
しないようにラツトの頭部から前肢にかけて黒布
袋で覆つた。また、比較のため注射４時間前にパ
ツプ剤を貼付しない対照群についても同様の試験
を行なつた。結果を第４〜６表に示す。
浮腫率（％）＝Vt−Vn／Vn×100
Vn：カラゲニン注射前の足容積
Vt：カラゲニン注射４時間後の足容積
浮腫抑制率（％）＝Ec−Et／Ec×100
Ec：対照群の平均浮腫率
Et：パツプ剤貼付群の平均浮腫率[Table] Furthermore, for comparison, gels, creams, and poultices with the following formulations were prepared. [Comparative example 14] Gel carboxyvinyl polymer 1.5% Propylene glycol 10.0% Triethanolamine 1.0% Indomethacin 0.5% Glycol salicylate 2.5% Ethanol 35.0% Water Remaining meter 100.0% [Comparative example 15] Creamcetanol 7.0% Stearic acid 3.0 Adipic acid Diisopropyl 5.0 Liquid paraffin 5.0 Glycerin 10.0 POE (20) Sorbitan monostearate 4.0 Sorbitan monostearate 1.2 Propyl paraoxybenzoate 0.05 Methyl paraoxybenzoate 0.05 Indomethacin 0.5 Glycol salicylate 2.5 Water Fuel gauge 100.0% [Comparative Example 16] thickener gelatin 5.0% Sodium carboxymethyl cellulose 6.0 Glycerin 35.0 Castor oil 1.0 POE (20) Sorbitan monooleate 1.0 Kaolin 10.0 Potassium aluminum sulfate 0.02 Citric acid 0.01 Indomethacin 0.5 Glycol salicylate 2.5 Water Remaining meter 100.0% Next, the above Examples 1 to 9, Experiments 1 and 2 below were conducted using the external preparations of Comparative Examples 1 to 16. Experiment 1 The following carrageenan foot edema suppression test was carried out in Example 1.
The anti-inflammatory effects of the external preparations of Comparative Examples 1 to 9 and Comparative Examples 1 to 16 were investigated. Carrageenin paw edema suppression test Using a group of 10 male Wistar rats weighing 140 to 160 g, the paw volume of the right hind paw of each rat was measured using a volume differential meter (Vgo).
After measuring with a 1% carrageenan suspension (inflammatory agent) (manufactured by Basile), 0.1 ml of a 1% carrageenan suspension (inflammatory agent) was subcutaneously injected into each footpad. The patch was pasted on the right hind leg 4 hours before the injection of the inflammatory agent, and the volume of the right hind leg after the injection was measured using the meter mentioned above.The edema rate and each patch were calculated using the following formula from the difference in the paw volume before and after the injection. The edema suppression rate of the agent was determined (500 mg of each of the gel of Comparative Example 14 and the cream of Comparative Example 15 was applied to the right hind leg). In order to prevent the rats from biting or licking the plaster applied during the test, the rat's head and forelimbs were covered with a black cloth bag. For comparison, a similar test was also conducted on a control group in which no poultice was applied 4 hours before injection. The results are shown in Tables 4-6. Edema rate (%) = Vt - Vn / Vn × 100 Vn: Paw volume before carrageenin injection Vt: Paw volume 4 hours after carrageenin injection Edema suppression rate (%) = Ec - Et / Ec × 100 Ec: of control group Average edema rate Et: Average edema rate in the plaster group
【表】【table】
【表】【table】
【表】
第４〜６表の結果より、水性パツプ基材にイン
ドメタシンと共にメントールとカンフルとの固溶
体及び／又はサリチル酸グリコールを配合した実
施例１〜13のパツプ剤（本発明パツプ剤）は、優
れた消炎鎮痛作用を示すことが認められた。ま
た、メントールとカンフルとの固溶体及び／又は
サリチル酸グリコールをインドメタシンの１重量
倍以上、特に５重量倍以上配合したものは特に消
炎鎮痛作用が高いことが認められた。これに対
し、インドメタシンのみを配合した比較例２，７
のパツプ剤は消炎鎮痛作用が低く、本発明パツプ
剤においてはインドメタシンが溶解状態で安定に
配合され、その経皮吸収率が高いことが認められ
た。また、第４表の結果から明らかなように、ポ
リアクリル酸及びポリアクリル酸塩を含有し、更
にカルボキシメチルセルロースナトリウム及び／
又はアルギン酸アルカリ金属塩を含有する多価金
属イオン架橋型含水ゲル基材に対し、インドメタ
シン及びメントールとカンフルとの固溶体又はサ
リチル酸グリコールを配合した本発明の水性パツ
プ剤（実施例１〜３）は優れた浮腫抑制率を与
え、消炎鎮痛作用に優れていることが認められ
る。これに対し、実施例２とインドメタシン及び
サリチル酸グリコール量が同量である比較例14〜
16の外用剤は、実施例２の浮腫抑制率の半分以下
で、本発明のパツプ剤と比較して消炎鎮痛作用が
かなり劣るものであることが認められた。即ち、
比較例14のゲルはカルボキシビニルポリマーをア
ミンでゲル化したものであり、また比較例16のパ
ツプ剤はゼラチンとカルボキシメチルセルロース
ナトリウムを含むゼラチン基材であるが、これら
は本発明に係るポリアクリル酸及びポリアクリル
酸塩を含有し、更にカルボキシメチルセルロース
ナトリウム及び／又はアルギン酸塩を含有する多
価金属イオン架橋型含水ゲル基材（非ゼラチン基
材）を用いた場合に比べて浮腫抑制率がかなり低
いものである。更に、比較例15のクリームも同様
に浮腫抑制率が低く、従つて本発明に係るポリア
クリル酸及びポリアクリル酸塩を含有し、更にカ
ルボキシメチルセルロースナトリウム及び／又は
アルギン酸アルカリ金属塩を含有する多価金属イ
オン架橋型含水ゲル基材とインドメタシン及びメ
ントールとカンフルとの固溶体、サリチル酸グリ
コールとの組合わせが優れた効果を与えることが
認められた。
実験 ２
健常男子20名の上腕部に実施例１〜９、比較例
１〜13のパツプ剤をそれぞれ貼付し、48時間クロ
ーズドパツチテストによりその皮膚刺激性を調べ
た。
結果は被験者20名全員が全てのパツプ剤につい
て無反応であり、実施例１〜９、比較例１〜13の
水性パツプ基材は皮膚に対する刺激性が低く、安
全性が高いことが認められた。
なお、上記パツプ剤はいずれも傾斜角30度にお
けるボールタツク測定による粘着力の値が20程度
であり、粘着力が強く、皮膚に対して安定に貼着
するものであつた。[Table] From the results in Tables 4 to 6, the plasters of Examples 1 to 13 (the plasters of the present invention) in which indomethacin, a solid solution of menthol and camphor, and/or glycol salicylate were blended in the aqueous plaster base material were superior. It was observed that it exhibited anti-inflammatory and analgesic effects. It was also found that products containing a solid solution of menthol and camphor and/or glycol salicylate of 1 times or more, particularly 5 times or more by weight of indomethacin had particularly high anti-inflammatory and analgesic effects. In contrast, Comparative Examples 2 and 7 containing only indomethacin
It was found that the poultices of the present invention have a low anti-inflammatory and analgesic effect, and the poultices of the present invention contain indomethacin stably in a dissolved state and have a high percutaneous absorption rate. Furthermore, as is clear from the results in Table 4, it contains polyacrylic acid and polyacrylate, and further contains sodium carboxymethyl cellulose and/or
Or, the aqueous poultices of the present invention (Examples 1 to 3) in which indomethacin and a solid solution of menthol and camphor or glycol salicylate are blended with a polyvalent metal ion crosslinked hydrogel base containing an alginate alkali metal salt are excellent. It is recognized that it has a high edema suppression rate and has excellent anti-inflammatory and analgesic effects. On the other hand, Comparative Examples 14 to 14 have the same amounts of indomethacin and glycol salicylate as Example 2
The external preparation No. 16 had less than half the edema suppression rate of Example 2, and was found to have considerably inferior anti-inflammatory and analgesic effects compared to the poultice of the present invention. That is,
The gel of Comparative Example 14 is a gelatinized carboxyvinyl polymer with amine, and the poultice of Comparative Example 16 is a gelatin base material containing gelatin and sodium carboxymethylcellulose, but these are gelatin base materials containing gelatin and carboxymethyl cellulose sodium. The edema suppression rate is considerably lower than when using a polyvalent metal ion crosslinked hydrogel base material (non-gelatin base material) containing polyacrylate and sodium carboxymethyl cellulose and/or alginate. It is something. Furthermore, the cream of Comparative Example 15 also has a low edema suppression rate, and therefore contains polyacrylic acid and polyacrylate according to the present invention, and further contains sodium carboxymethyl cellulose and/or alkali metal alginate. It has been found that the combination of a metal ion crosslinked hydrogel base material, indomethacin, a solid solution of menthol and camphor, and glycol salicylate provides an excellent effect. Experiment 2 The poultices of Examples 1 to 9 and Comparative Examples 1 to 13 were applied to the upper arms of 20 healthy men, and their skin irritation was examined by a 48-hour closed patch test. The results showed that all 20 subjects had no reaction to all poultices, and the aqueous poultice base materials of Examples 1 to 9 and Comparative Examples 1 to 13 were recognized to have low irritation to the skin and to be highly safe. . All of the above poultices had adhesive strength values of about 20 as determined by ball tack measurement at an inclination angle of 30 degrees, indicating strong adhesive strength and stable adhesion to the skin.
Claims (1)
し、更にカルボキシメチルセルロースナトリウム
及び／又はアルギン酸アルカリ金属塩を含有する
多価金属イオン架橋型含水ゲル基材に、インドメ
タシンを配合すると共に、メントールとカンフル
との固溶体及び／又はサリチル酸グリコールを配
合してなることを特徴とする水性パツプ剤。 ２ ポリアクリル酸とポリアクリル酸塩との配合
比が重量比で８：２〜１：９である特許請求の範
囲第１項記載の水性パツプ剤。 ３ 基材のPHが４〜6.5である特許請求の範囲第
１項又は第２項記載の水性パツプ剤。 ４ メントールとカンフルとの固溶体及び／又は
サリチル酸グリコールをインドメタシンの１重量
倍以上配合した特許請求の範囲第１項乃至第３項
いずれか記載の水性パツプ剤。 ５ インドメタシンの配合量が基材全体の0.1〜
５重量％である特許請求の範囲第１項乃至第４項
いずれか記載の水性パツプ剤。 ６ メントールとカンフルとの固溶体及び／又は
サリチル酸グリコールの配合量が基材全体の0.5
〜30重量％である特許請求の範囲第１項乃至第５
項いずれか記載の水性パツプ剤。[Claims] 1. Indomethacin is blended into a polyvalent metal ion crosslinked hydrogel base material containing polyacrylic acid and polyacrylate, and further containing sodium carboxymethyl cellulose and/or alginate alkali metal salt. , a solid solution of menthol and camphor, and/or glycol salicylate. 2. The aqueous poultice according to claim 1, wherein the blending ratio of polyacrylic acid and polyacrylate is 8:2 to 1:9 by weight. 3. The aqueous poultice according to claim 1 or 2, wherein the base material has a pH of 4 to 6.5. 4. The aqueous poultice according to any one of claims 1 to 3, which contains a solid solution of menthol and camphor and/or glycol salicylate in an amount of at least 1 times the weight of indomethacin. 5 The blending amount of indomethacin is 0.1 to 0.1 of the entire base material.
The aqueous poultice according to any one of claims 1 to 4, which contains 5% by weight. 6 The amount of solid solution of menthol and camphor and/or glycol salicylate is 0.5 of the total base material.
~30% by weight Claims 1 to 5
An aqueous poultice as described in any of the above.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13247384A JPS6112614A (en) | 1984-06-27 | 1984-06-27 | Drug for external use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP13247384A JPS6112614A (en) | 1984-06-27 | 1984-06-27 | Drug for external use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6112614A JPS6112614A (en) | 1986-01-21 |
| JPH0436134B2 true JPH0436134B2 (en) | 1992-06-15 |
Family
ID=15082195
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP13247384A Granted JPS6112614A (en) | 1984-06-27 | 1984-06-27 | Drug for external use |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6112614A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011074033A (en) * | 2009-09-30 | 2011-04-14 | Kobayashi Pharmaceutical Co Ltd | Pharmaceutical composition for external use |
| JPWO2016104226A1 (en) * | 2014-12-22 | 2017-09-28 | 久光製薬株式会社 | Poultice |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH064530B2 (en) * | 1985-02-23 | 1994-01-19 | 日本化薬株式会社 | Hydrophilic base |
| JPH07106979B2 (en) * | 1988-05-27 | 1995-11-15 | 久光製薬株式会社 | Transdermal formulation |
| ATE143603T1 (en) * | 1990-03-30 | 1996-10-15 | Yasunori Morimoto | TRANSDERMAL ABSORBABLE AGENT WITH MORPHINE HYDROCHLORIDE |
| JPH04193826A (en) * | 1990-11-27 | 1992-07-13 | Shirogane Seiyaku Kk | Sodium dichlofenac-containing percutaneous absorption type antiinflammatory-analgesic patch |
| US7138394B2 (en) * | 2002-09-27 | 2006-11-21 | Alpharx Inc. | Vehicle for topical delivery of anti-inflammatory compounds |
| JP2004123633A (en) * | 2002-10-03 | 2004-04-22 | Medorekkusu:Kk | Preparation for external use |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5829706A (en) * | 1981-08-14 | 1983-02-22 | Toko Yakuhin Kogyo Kk | Antiphlogistic and analgesic agent for external use |
-
1984
- 1984-06-27 JP JP13247384A patent/JPS6112614A/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5829706A (en) * | 1981-08-14 | 1983-02-22 | Toko Yakuhin Kogyo Kk | Antiphlogistic and analgesic agent for external use |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011074033A (en) * | 2009-09-30 | 2011-04-14 | Kobayashi Pharmaceutical Co Ltd | Pharmaceutical composition for external use |
| JPWO2016104226A1 (en) * | 2014-12-22 | 2017-09-28 | 久光製薬株式会社 | Poultice |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6112614A (en) | 1986-01-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS646173B2 (en) | ||
| JPH0530807B2 (en) | ||
| WO1997028793A1 (en) | External preparation containing tranilast and process for producing the same | |
| JPH0338250B2 (en) | ||
| WO1996004902A1 (en) | Composition of external preparation | |
| JP4596751B2 (en) | Anti-inflammatory analgesic patch | |
| JP2001513093A (en) | Topical Nimusulide gel system | |
| JPH0436134B2 (en) | ||
| WO1994002119A1 (en) | Percutaneously administrable base composition and drug composition prepared therefrom | |
| JPS6310716A (en) | Beta-stimulation agent for external use | |
| JPS61275212A (en) | Ketoprofen-containing poultice | |
| JPH0794378B2 (en) | Aerosol | |
| JPH08243377A (en) | Alcohol-containing gel body | |
| JP3193161B2 (en) | Transdermal absorption preparation | |
| JPS60260513A (en) | Poultice | |
| JP2023551417A (en) | Brusingel plaster, its manufacturing method and use | |
| JP3382032B2 (en) | Indomethacin patch | |
| JPH11199519A (en) | Preparation for external use for skin | |
| JP3002733B2 (en) | Indomethacin-containing patch | |
| JP2005060386A (en) | External preparation for skin | |
| JPH0555485B2 (en) | ||
| JPH0338245B2 (en) | ||
| JP2003113077A (en) | Plaster | |
| JPH11199482A (en) | Preparation composition for external use | |
| JP3612731B2 (en) | Anti-inflammatory analgesic topical |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| LAPS | Cancellation because of no payment of annual fees |