JP7398274B2 - External composition - Google Patents
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- JP7398274B2 JP7398274B2 JP2019236394A JP2019236394A JP7398274B2 JP 7398274 B2 JP7398274 B2 JP 7398274B2 JP 2019236394 A JP2019236394 A JP 2019236394A JP 2019236394 A JP2019236394 A JP 2019236394A JP 7398274 B2 JP7398274 B2 JP 7398274B2
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- Japan
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- 239000000203 mixture Substances 0.000 title claims description 88
- JDLSRXWHEBFHNC-UHFFFAOYSA-N Ufenamate Chemical compound CCCCOC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 JDLSRXWHEBFHNC-UHFFFAOYSA-N 0.000 claims description 30
- 229950010121 ufenamate Drugs 0.000 claims description 30
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 28
- 239000007788 liquid Substances 0.000 claims description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 239000004094 surface-active agent Substances 0.000 claims description 19
- 239000004215 Carbon black (E152) Substances 0.000 claims description 17
- 229930195733 hydrocarbon Natural products 0.000 claims description 17
- 150000002430 hydrocarbons Chemical class 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 10
- 238000002156 mixing Methods 0.000 claims description 4
- 239000003921 oil Substances 0.000 description 47
- 239000006185 dispersion Substances 0.000 description 40
- 239000012071 phase Substances 0.000 description 28
- 230000000694 effects Effects 0.000 description 26
- 239000008346 aqueous phase Substances 0.000 description 18
- 238000009472 formulation Methods 0.000 description 11
- 239000000839 emulsion Substances 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 238000000926 separation method Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 229940057995 liquid paraffin Drugs 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- -1 butyl flufenamic acid Chemical compound 0.000 description 3
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 2
- LVYLCBNXHHHPSB-UHFFFAOYSA-N 2-hydroxyethyl salicylate Chemical compound OCCOC(=O)C1=CC=CC=C1O LVYLCBNXHHHPSB-UHFFFAOYSA-N 0.000 description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 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
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229960004194 lidocaine Drugs 0.000 description 2
- 238000004519 manufacturing process 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
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- RGOVYLWUIBMPGK-UHFFFAOYSA-N nonivamide Chemical compound CCCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 RGOVYLWUIBMPGK-UHFFFAOYSA-N 0.000 description 2
- 239000007764 o/w emulsion Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 1
- OHILSKSRDDTCIR-WKSAPEMMSA-N (8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one;hydrochloride Chemical compound Cl.C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O OHILSKSRDDTCIR-WKSAPEMMSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 description 1
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-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
- IJALWSVNUBBQRA-UHFFFAOYSA-N 4-Isopropyl-3-methylphenol Chemical compound CC(C)C1=CC=C(O)C=C1C IJALWSVNUBBQRA-UHFFFAOYSA-N 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 235000002568 Capsicum frutescens Nutrition 0.000 description 1
- 240000008574 Capsicum frutescens Species 0.000 description 1
- WJLVQTJZDCGNJN-UHFFFAOYSA-N Chlorhexidine hydrochloride Chemical compound Cl.Cl.C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 WJLVQTJZDCGNJN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
- VNQABZCSYCTZMS-UHFFFAOYSA-N Orthoform Chemical compound COC(=O)C1=CC=C(O)C(N)=C1 VNQABZCSYCTZMS-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 description 1
- KCLANYCVBBTKTO-UHFFFAOYSA-N Proparacaine Chemical compound CCCOC1=CC=C(C(=O)OCCN(CC)CC)C=C1N KCLANYCVBBTKTO-UHFFFAOYSA-N 0.000 description 1
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 1
- FPVRUILUEYSIMD-RPRRAYFGSA-N [(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(OC(C)=O)[C@@]1(C)C[C@@H]2O FPVRUILUEYSIMD-RPRRAYFGSA-N 0.000 description 1
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 229960001716 benzalkonium Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- 229960005274 benzocaine Drugs 0.000 description 1
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 1
- CYDRXTMLKJDRQH-UHFFFAOYSA-N benzododecinium Chemical compound CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 CYDRXTMLKJDRQH-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229950004580 benzyl nicotinate Drugs 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- QRZAKQDHEVVFRX-UHFFFAOYSA-N biphenyl-4-ylacetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1C1=CC=CC=C1 QRZAKQDHEVVFRX-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960003150 bupivacaine Drugs 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
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- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229960003333 chlorhexidine gluconate Drugs 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
- 229960004504 chlorhexidine hydrochloride Drugs 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 1
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 1
- 229960001747 cinchocaine Drugs 0.000 description 1
- PUFQVTATUTYEAL-UHFFFAOYSA-N cinchocaine Chemical compound C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCCN(CC)CC)=C21 PUFQVTATUTYEAL-UHFFFAOYSA-N 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
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- 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
- 229960001378 dequalinium chloride Drugs 0.000 description 1
- LTNZEXKYNRNOGT-UHFFFAOYSA-N dequalinium chloride Chemical compound [Cl-].[Cl-].C1=CC=C2[N+](CCCCCCCCCC[N+]3=C4C=CC=CC4=C(N)C=C3C)=C(C)C=C(N)C2=C1 LTNZEXKYNRNOGT-UHFFFAOYSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
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- 230000003631 expected effect Effects 0.000 description 1
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- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 description 1
- AHXDSVSZEZHDLV-UHFFFAOYSA-N mesulfen Chemical compound CC1=CC=C2SC3=CC(C)=CC=C3SC2=C1 AHXDSVSZEZHDLV-UHFFFAOYSA-N 0.000 description 1
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- 239000002674 ointment Substances 0.000 description 1
- 229950006098 orthocaine Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
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- 230000035790 physiological processes and functions Effects 0.000 description 1
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- BOFKYYWJAOZDPB-FZNHGJLXSA-N prednival Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CO)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O BOFKYYWJAOZDPB-FZNHGJLXSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
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- 230000001737 promoting effect Effects 0.000 description 1
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- 239000008213 purified water Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000017520 skin disease Diseases 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
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- 229960004306 sulfadiazine Drugs 0.000 description 1
- 229960002372 tetracaine Drugs 0.000 description 1
- GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
本発明は、ウフェナマートを含有し、水相及び油相相互の混ざりやすさが向上した外用組成物に関する。 The present invention relates to a composition for external use containing ufenamate and having improved mutual miscibility between an aqueous phase and an oil phase.
ウフェナマートは、医薬品の非ステロイド系抗炎症剤として皮膚疾患の治療に用いられている。一方で、ウフェナマートは水難溶性の薬剤のため、水を含む外用医薬品等の製剤中に安定に配合することは困難であった。 Ufenamate is used as a pharmaceutical non-steroidal anti-inflammatory agent to treat skin diseases. On the other hand, since ufenamate is a poorly water-soluble drug, it has been difficult to stably incorporate it into formulations such as external medicines that contain water.
これに対して、ウフェナマートを外用組成物に安定に配合する技術が提案されている。例えば、特許文献１には、ウフェナマート及びＨＬＢが８～１５である乳化剤を含む油相中に水を加えて乳化させ、そのエマルジョン（乳化粒子）の平均粒子径が０．５μｍ以下の微細エマルジョンからなるＯ／Ｗ型乳化製剤により、ウフェナマートを含有する製剤の安定化を図ることが記載されている。また、特許文献２には、ウフェナマート、グリチルレチン酸又はそのエステル、リドカイン、油分、界面活性剤、水を配合することを特徴とするウフェナマート含有皮膚外用剤が優れた安定性を有することが記載されている。 In response to this, a technique has been proposed for stably incorporating ufenamate into a composition for external use. For example, in Patent Document 1, water is added to an oil phase containing ufenamate and an emulsifier having an HLB of 8 to 15 to emulsify it, and a fine emulsion with an average particle diameter of 0.5 μm or less is produced. It is described that a preparation containing ufenamate is stabilized by an O/W emulsion preparation. Further, Patent Document 2 describes that a topical skin preparation containing ufenamate, which is characterized by containing ufenamate, glycyrrhetinic acid or its ester, lidocaine, an oil, a surfactant, and water, has excellent stability. There is.
これまでのウフェナマート含有外用剤は、安定化効果が謳われていても、水相及び油相自体が本質的に混ざらないため、分散系を構築するには界面活性剤に頼らざるを得ない。事実、界面活性剤を用いない場合は、水相と油相とは非常に混ざりにくい。油性基剤には、乳化剤としての機能も知られているミリスチン酸イソプロピルが配合されることが多いが、ウフェナマート含有外用剤においては、油性基剤にミリスチン酸イソプロピルが配合されていても、水相と油相はやはり非常に混ざりにくい。特に、油性基剤に疎水性の高い炭化水素油が用いられている場合、水相と油相との混ざりにくさは格別顕著となる。 Even though conventional ufenamate-containing external preparations claim to have a stabilizing effect, the aqueous phase and oil phase are essentially immiscible, so they have to rely on surfactants to construct a dispersion system. In fact, in the absence of surfactants, the aqueous and oil phases are very immiscible. Isopropyl myristate, which is known to function as an emulsifier, is often blended into the oil base, but in topical preparations containing ufenamate, even if isopropyl myristate is blended into the oil base, the aqueous phase The oil phase is still very difficult to mix. In particular, when a highly hydrophobic hydrocarbon oil is used as the oily base, the difficulty in mixing the aqueous phase and the oil phase becomes particularly pronounced.
ここで、もし、互いに混ざりやすい水相及び油相の組み合わせが見いだされれば、界面活性剤を用いなくても優れた分散系を構築することができるだけでなく、更に界面活性剤を用いれば、より一層優れた乳化安定性が得られると考えられる。 Here, if a combination of aqueous and oil phases that are easily miscible with each other is found, not only can an excellent dispersion system be constructed without using a surfactant, but it is also possible to construct an excellent dispersion system by using a surfactant. It is thought that even better emulsion stability can be obtained.
そこで、本発明は、ウフェナマートを含有し、且つ液状炭化水素を油性基剤として含みながらも、互いに混ざりやすい水相及び油相の組み合わせを含む外用組成物を提供することを目的とする。 Therefore, an object of the present invention is to provide a composition for external use that contains ufenamate and a combination of an aqueous phase and an oil phase that are easily miscible with each other, while also containing a liquid hydrocarbon as an oily base.
本発明者は、ウフェナマートを含有し、且つ液状炭化水素を油性基剤として含む含水外用組成物について鋭意検討を行ったところ、Ｎ－メチル－２－ピロリドンを配合することで、界面活性剤を用いなくても優れた分散系を構築できることを予期せずして見出した。本発明は、この知見に基づいて更に検討を重ねることにより完成したものである。 The present inventor conducted intensive studies on a water-containing topical composition containing ufenamate and a liquid hydrocarbon as an oily base, and found that by incorporating N-methyl-2-pyrrolidone, a surfactant can be used. We unexpectedly discovered that it is possible to construct an excellent dispersion system even without the use of The present invention was completed through further studies based on this knowledge.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項１． （Ａ）ウフェナマート、（Ｂ）Ｎ－メチル－２－ピロリドン、（Ｃ）液状炭化水素、及び（Ｄ）水を含有する外用組成物。
項２． 前記（Ａ）成分１重量部当たり、前記（Ｃ）成分が０．１重量部以上含まれる、項１に記載の外用組成物。
項３． 前記（Ｃ）成分１重量部当たり、前記（Ｄ）成分が１０重量部以上含まれる、項１又は２に記載の外用組成物。
項４． 前記（Ｄ）成分の含有量が６０重量％以上である、項１～３のいずれかに記載の外用組成物。
項５． 界面活性剤の含有量が０．１重量％以下である、項１～４のいずれかに記載の外用組成物。
項６． （Ａ）ウフェナマート、（Ｃ）液状炭化水素、及び（Ｄ）水を有する外用組成物において、（Ｂ）Ｎ－メチル－２－ピロリドンを配合する、外用組成物の分散化方法。
That is, the present invention provides the following aspects of the invention.
Item 1. A composition for external use containing (A) ufenamate, (B) N-methyl-2-pyrrolidone, (C) liquid hydrocarbon, and (D) water.
Item 2. Item 2. The external composition according to Item 1, wherein the component (C) is contained in an amount of 0.1 part by weight or more per 1 part by weight of the component (A).
Item 3. Item 3. The external composition according to Item 1 or 2, wherein the component (D) is contained in an amount of 10 parts by weight or more per 1 part by weight of the component (C).
Item 4. Item 4. The external composition according to any one of Items 1 to 3, wherein the content of the component (D) is 60% by weight or more.
Item 5. Item 5. The external composition according to any one of Items 1 to 4, wherein the content of the surfactant is 0.1% by weight or less.
Item 6. A method for dispersing a composition for external use, which comprises blending (B) N-methyl-2-pyrrolidone in a composition for external use comprising (A) ufenamate, (C) a liquid hydrocarbon, and (D) water.
本発明によると、ウフェナマートを含有し、且つ液状炭化水素を油性基剤として含む外用組成物に用いる、互いに混ざりやすい水相及び油相の組み合わせを提供することができる。このため、本発明の外用組成物は、水相及び油相が混ざりやすく、優れた分散系を構築する（以下において、このような効果を、分散化効果とも記載する。）ことができる。 According to the present invention, it is possible to provide a combination of an aqueous phase and an oil phase that are easily miscible with each other and are used in an external composition containing ufenamate and a liquid hydrocarbon as an oily base. Therefore, in the external composition of the present invention, the aqueous phase and oil phase are easily mixed, and an excellent dispersion system can be constructed (hereinafter, such an effect will also be referred to as a dispersion effect).
１．外用組成物
本発明の外用組成物は、（Ａ）ウフェナマート（以下において、「（Ａ）成分」とも記載する）、（Ｂ）Ｎ－メチル－２－ピロリドン（以下において、「（Ｂ）成分」とも記載する）、（Ｃ）液状炭化水素（以下において、「（Ｃ）成分」とも記載する）、及び（Ｄ）水（以下において、「（Ｄ）成分」とも記載する）を含有することを特徴とする。以下、本発明の外用組成物について詳述する。
1. External composition The external composition of the present invention contains (A) ufenamate (hereinafter also referred to as "component (A)"), (B) N-methyl-2-pyrrolidone (hereinafter referred to as "component (B)"). (also hereinafter referred to as "(D) component"), (C) liquid hydrocarbon (hereinafter also referred to as "(C) component"), and (D) water (hereinafter also referred to as "(D) component"). Features. Hereinafter, the external composition of the present invention will be explained in detail.
（Ａ）ウフェナマート
本発明の外用組成物は、（Ａ）成分としてウフェナマートを含む。ウフェナマートは、フルフェナム酸ブチルとも称され、水難溶性の非ステロイド性抗炎症薬として公知の成分である。ウフェナマートを含む外用組成物に用いられる水相及び油相は非常に混ざりにくいが、本発明の外用組成物は、水相及び油相が混ざりやすく、優れた分散系を構築することができる。
(A) Ufenamate The external composition of the present invention contains ufenamate as the component (A). Ufenamate is also called butyl flufenamic acid, and is a component known as a poorly water-soluble non-steroidal anti-inflammatory drug. Although the aqueous phase and the oil phase used in the external composition containing ufenamate are very difficult to mix, in the external composition of the present invention, the aqueous phase and the oil phase are easily mixed, and an excellent dispersion system can be constructed.
本発明の外用組成物における（Ａ）成分の含有量については特に限定されず、付与すべき効能などに応じて適宜設定されるが、例えば１～２０重量％、好ましくは２～１０重量％、更に好ましくは３～７重量％が挙げられる。 The content of component (A) in the external composition of the present invention is not particularly limited, and is appropriately set depending on the efficacy to be imparted, but for example, 1 to 20% by weight, preferably 2 to 10% by weight, More preferably, the amount is 3 to 7% by weight.
（Ｂ）Ｎ－メチル－２－ピロリドン
本発明の外用組成物は、（Ｂ）成分としてＮ－メチル－２－ピロリドンを含む。ウフェナマートを含む外用組成物に用いられる水相及び油相は非常に混ざりにくいが、本発明の外用組成物は、Ｎ－メチル－２－ピロリドンを配合することで、水相及び油相が混ざりやすく、優れた分散系を構築することができる。
(B) N-Methyl-2-pyrrolidone The external composition of the present invention contains N-methyl-2-pyrrolidone as the component (B). The aqueous phase and oil phase used in external compositions containing ufenamate are very difficult to mix, but in the external composition of the present invention, by incorporating N-methyl-2-pyrrolidone, the aqueous phase and oil phase are easily mixed. , it is possible to construct an excellent dispersion system.
本発明の外用組成物における（Ｂ）成分の含有量としては特に限定されず、付与すべき分散化効果に応じて適宜設定されるが、例えば０．１重量％以上が挙げられる。より一層好ましい分散化効果を得る観点から、好ましくは０．５重量％以上、より好ましくは１重量％以上、さらに好ましくは５重量％以上が挙げられる。（Ｂ）成分の含有量の範囲の上限としては特に限定されないが、例えば１０重量％以下、好ましくは８重量％以下、より好ましくは６重量％以下が挙げられる。 The content of component (B) in the external composition of the present invention is not particularly limited, and is appropriately set depending on the dispersion effect to be imparted, and may be, for example, 0.1% by weight or more. From the viewpoint of obtaining a more preferable dispersion effect, the content is preferably 0.5% by weight or more, more preferably 1% by weight or more, and still more preferably 5% by weight or more. The upper limit of the content of component (B) is not particularly limited, but may be, for example, 10% by weight or less, preferably 8% by weight or less, and more preferably 6% by weight or less.
本発明の外用組成物において、（Ａ）成分の含有量に対する（Ｂ）成分の含有量の比率は、上記各成分の含有量によって定まるが、より一層好ましい分散化効果を得る観点から、（Ａ）成分１重量部に対する（Ｂ）成分の含有量として、０．１重量部以上、好ましくは０．２重量部以上、より好ましくは１重量部以上が挙げられる。（Ａ）成分１重量部に対する（Ｂ）成分の含有量の範囲の上限としては特に限定されないが、例えば２重量部以下、好ましくは１．６重量部以下、より好ましくは１．２重量部以下が挙げられる。 In the external composition of the present invention, the ratio of the content of the component (B) to the content of the component (A) is determined by the content of each of the above components. The content of component (B) per 1 part by weight of component () is 0.1 part by weight or more, preferably 0.2 part by weight or more, and more preferably 1 part by weight or more. The upper limit of the content of component (B) per 1 part by weight of component (A) is not particularly limited, but is, for example, 2 parts by weight or less, preferably 1.6 parts by weight or less, more preferably 1.2 parts by weight or less. can be mentioned.
（Ｃ）液状炭化水素
本発明の外用組成物は、（Ｃ）成分として液状炭化水素を含む。液状炭化水素とは、２５℃で液状を呈する炭化水素油をいう。ウフェナマートを含む外用組成物に用いられる油相に液状炭化水素が含まれていると、水相及び油相は極めて混ざりにくいが、本発明の外用組成物では、水相及び油相が混ざりやすく、優れた分散系を構築することができる。
(C) Liquid Hydrocarbon The external composition of the present invention contains a liquid hydrocarbon as the component (C). Liquid hydrocarbon refers to hydrocarbon oil that is liquid at 25°C. When the oil phase used in the external composition containing ufenamate contains a liquid hydrocarbon, the aqueous phase and the oil phase are extremely difficult to mix, but in the external composition of the present invention, the aqueous phase and the oil phase easily mix, An excellent dispersion system can be constructed.
液状炭化水素としては、流動パラフィン、スクワレン、スクワラン等が挙げられ、好ましくは流動パラフィンが挙げられる。 Examples of the liquid hydrocarbon include liquid paraffin, squalene, squalane, etc., and preferably liquid paraffin is used.
本発明の外用組成物における（Ｃ）成分の含有量としては特に限定されず、製剤形態等に応じて適宜設定されるが、例えば１重量％以上、好ましくは３重量％以上、より好ましくは４重量％以上、さらに好ましくは５重量％以上が挙げられる。（Ｃ）成分の含有量の範囲の上限としては特に限定されないが、例えば１０重量％以下、好ましくは８重量％以下、より好ましくは６重量％以下が挙げられる。 The content of component (C) in the external composition of the present invention is not particularly limited and is set appropriately depending on the formulation etc., but for example, 1% by weight or more, preferably 3% by weight or more, more preferably 4% by weight or more. The amount is preferably at least 5% by weight, more preferably at least 5% by weight. The upper limit of the content of component (C) is not particularly limited, but may be, for example, 10% by weight or less, preferably 8% by weight or less, and more preferably 6% by weight or less.
本発明の外用組成物において、油相の基剤成分の総量に対する（Ｃ）成分の含有量としては特に限定されないが、油相の基剤成分全体の総量１００重量部に対する（Ｃ）成分の含有量の比率として、例えば６０重量部以上が挙げられる。本発明の外用組成物は分散化効果に優れているため、油相の基剤成分において（Ｃ）成分が多く占めていても、効果的に分散化効果を得ることができる。このような観点から、油相の基剤成分全体の総量１００重量部に対する（Ｃ）成分の含有量の比率の好適な例として、好ましくは７０重量部以上、より好ましくは８０重量部以上、さらに好ましくは９０重量部以上、一層好ましくは９５重量部以上が挙げられる。 In the external composition of the present invention, the content of component (C) with respect to the total amount of base components in the oil phase is not particularly limited, but the content of component (C) with respect to 100 parts by weight of the total amount of base components in the oil phase. Examples of the amount ratio include 60 parts by weight or more. Since the external composition of the present invention has an excellent dispersing effect, it is possible to effectively obtain a dispersing effect even if component (C) occupies a large amount of the base component of the oil phase. From this point of view, a suitable example of the ratio of the content of component (C) to 100 parts by weight of the total base components of the oil phase is preferably 70 parts by weight or more, more preferably 80 parts by weight or more, and Preferably it is 90 parts by weight or more, more preferably 95 parts by weight or more.
（Ｄ）水
本発明の外用組成物は、（Ｄ）成分として水を含む。ウフェナマートを含む外用組成物に用いられる水相は油相と非常に混ざりにくいが、本発明の外用組成物は、水相が油相と混ざりやすく、優れた分散系を構築することができる。
(D) Water The external composition of the present invention contains water as the (D) component. The aqueous phase used in external compositions containing ufenamate is very difficult to mix with the oil phase, but in the external composition of the present invention, the aqueous phase easily mixes with the oil phase, making it possible to construct an excellent dispersion system.
本発明の外用組成物における（Ｄ）成分の含有量としては特に限定されず、製剤形態等に応じて適宜設定されるが、例えば６０重量％以上が挙げられる。本発明の外用組成物は分散化効果に優れているため、（Ｄ）成分の含有量が多くても、効果的に分散化効果を得ることができる。このような観点から、（Ｄ）成分の含有量の好適な例として、好ましくは６５重量％以上、より好ましくは７０重量％以上、さらに好ましくは７５重量％以上、一層好ましくは８０重量％以上が挙げられる。 The content of component (D) in the external composition of the present invention is not particularly limited, and is appropriately set depending on the formulation form, etc., and may be, for example, 60% by weight or more. Since the external composition of the present invention has an excellent dispersion effect, even if the content of component (D) is large, the dispersion effect can be effectively obtained. From this point of view, a suitable example of the content of component (D) is preferably 65% by weight or more, more preferably 70% by weight or more, even more preferably 75% by weight or more, and still more preferably 80% by weight or more. Can be mentioned.
（Ｄ）成分の含有量の範囲の上限としては特に限定されないが、より一層優れた分散化効果を得る観点から、９３重量％以下、好ましくは８９重量％以下、より好ましくは８５重量％以下が挙げられる。 The upper limit of the content range of component (D) is not particularly limited, but from the viewpoint of obtaining even better dispersion effects, it is 93% by weight or less, preferably 89% by weight or less, more preferably 85% by weight or less. Can be mentioned.
本発明の外用組成物において、（Ｃ）成分の含有量に対する（Ｄ）成分の含有量の比率は、上記各成分の含有量によって定まるが、例えば（Ｃ）成分１重量部に対する（Ｄ）成分の含有量として、例えば１０重量部以上が挙げられる。本発明の外用組成物は分散化効果に優れているため、（Ｄ）成分の含有比率が高くても、効果的に分散化効果を得ることができる。このような観点から、（Ｃ）成分１重量部に対する（Ｄ）成分の含有量の好適な例として、好ましくは１２重量部以上、より好ましくは１４重量部以上、一層好ましくは１６重量部以上が挙げられる。 In the external composition of the present invention, the ratio of the content of component (D) to the content of component (C) is determined by the content of each of the above components, for example, component (D) to 1 part by weight of component (C). Examples of the content include 10 parts by weight or more. Since the external composition of the present invention has an excellent dispersion effect, even if the content ratio of component (D) is high, the dispersion effect can be effectively obtained. From this point of view, a suitable example of the content of component (D) per 1 part by weight of component (C) is preferably 12 parts by weight or more, more preferably 14 parts by weight or more, even more preferably 16 parts by weight or more. Can be mentioned.
（Ｃ）成分１重量部に対する（Ｄ）成分の含有量の範囲の上限しては特に限定されないが、より一層優れた分散化効果を得る観点から、１８重量部以下、好ましくは１７．８重量部以下、より好ましくは１７.４重量部以下が挙げられる。 The upper limit of the content of component (D) per 1 part by weight of component (C) is not particularly limited, but from the viewpoint of obtaining even better dispersion effects, it is 18 parts by weight or less, preferably 17.8 parts by weight. parts by weight or less, more preferably 17.4 parts by weight or less.
本発明の外用組成物において、油性基剤の総量に対する（Ｄ）成分の含有量の比率は、上記各成分の含有量によって定まるが、例えば油性基剤の総量１重量部に対する（Ｄ）成分の含有量として、例えば１０重量部以上が挙げられる。本発明の外用組成物は分散化効果に優れているため、（Ｄ）成分の含有比率が高くても、効果的に分散化効果を得ることができる。このような観点から、油性基剤の総量１重量部に対する（Ｄ）成分の含有量の好適な例として、好ましくは１２重量部以上、より好ましくは１４重量部以上、一層好ましくは１６重量部以上が挙げられる。 In the external composition of the present invention, the ratio of the content of component (D) to the total amount of the oily base is determined by the content of each of the above components. The content may be, for example, 10 parts by weight or more. Since the external composition of the present invention has an excellent dispersion effect, even if the content ratio of component (D) is high, the dispersion effect can be effectively obtained. From this point of view, a suitable example of the content of component (D) per 1 part by weight of the total amount of the oily base is preferably 12 parts by weight or more, more preferably 14 parts by weight or more, even more preferably 16 parts by weight or more. can be mentioned.
油性基剤の総量１重量部に対する（Ｄ）成分の含有量の範囲の上限しては特に限定されないが、より一層優れた分散化効果を得る観点から、１８重量部以下、好ましくは１７．８重量部以下、より好ましくは１７重量部以下が挙げられる。 The upper limit of the content of component (D) per 1 part by weight of the total amount of the oily base is not particularly limited, but from the viewpoint of obtaining an even better dispersion effect, it is 18 parts by weight or less, preferably 17.8 parts by weight. The amount is preferably 17 parts by weight or less, more preferably 17 parts by weight or less.
その他の成分
本発明の外用組成物は、前述する成分の他に、必要に応じて、通常使用される他の添加剤が含まれていてもよい。このような添加剤としては、例えば、（Ｃ）成分以外の油性基剤（以下において、他の油性基剤とも記載する）、界面活性剤、多価アルコール、増粘剤、ｐＨ調節剤、緩衝剤、可溶化剤、キレート剤、防腐剤、保存剤、酸化防止剤、安定化剤、香料、着色料等が挙げられる。
Other Components In addition to the above-mentioned components, the external composition of the present invention may contain other commonly used additives, if necessary. Examples of such additives include oily bases other than component (C) (hereinafter also referred to as other oily bases), surfactants, polyhydric alcohols, thickeners, pH adjusters, and buffers. agents, solubilizers, chelating agents, preservatives, preservatives, antioxidants, stabilizers, fragrances, coloring agents, and the like.
他の油性基剤としては薬学的又は香粧学的に許容されることを限度として特に制限されないが、例えば、（Ｃ）成分以外の液状油（２５℃において液状を呈する油）、固形油（２５℃において液状を呈する油）、高級アルコール等が挙げられる。これらの油分は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 Other oil bases are not particularly limited as long as they are pharmaceutically or cosmetically acceptable, but examples include liquid oils other than component (C) (oils that are liquid at 25°C), solid oils ( Examples include oils that are liquid at 25°C, higher alcohols, and the like. These oils may be used alone or in combination of two or more.
本発明の外用組成物は、分散化効果に優れているため、界面活性剤を含まなくても、効果的に分散化効果を得ることができるため、好適な例においては、界面活性剤を含まない。しかしながら、本発明の外用組成物は、更に界面活性剤を含むことも許容する。界面活性剤を含むことで、分散状態をより一層安定化させることができる。 Since the external composition of the present invention has an excellent dispersion effect, it is possible to effectively obtain a dispersion effect even without containing a surfactant. do not have. However, the external composition of the present invention may also contain a surfactant. By including a surfactant, the dispersion state can be further stabilized.
界面活性剤としては、薬学的又は香粧学的に許容されることを限度として特に制限されないが、例えば、ノニオン性界面活性剤、アニオン性界面活性剤、カチオン性界面活性剤、両性界面活性剤等が挙げられる。これらの界面活性剤は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The surfactant is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, but examples include nonionic surfactants, anionic surfactants, cationic surfactants, and amphoteric surfactants. etc. These surfactants may be used alone or in combination of two or more.
本発明の外用組成物における界面活性剤の含有量としては特に限定されず、通常のウフェナマート外用組成物に含まれる程度の量で含むことができる。一方、本発明の外用組成物が分散化効果に優れているため、界面活性剤を含まなくても効果的に分散化効果を得ることができるため、界面活性剤の量を、通常のウフェナマート外用組成物に含まれる程度の量に比べて削減することができる。このような観点から、界面活性剤の含有量の好適な例としては、好ましくは０．１重量％以下、より好ましくは０．０１重量％以下、更に好ましくは０．００１重量％以下、一層好ましくは０．０００５重量％以下が挙げられる。 The content of the surfactant in the external composition of the present invention is not particularly limited, and can be contained in an amount that is included in a normal ufenamate external composition. On the other hand, since the topical composition of the present invention has an excellent dispersion effect, it is possible to effectively obtain the dispersion effect even without containing a surfactant. The amount can be reduced compared to the amount contained in the composition. From this point of view, preferred examples of the surfactant content include: preferably 0.1% by weight or less, more preferably 0.01% by weight or less, even more preferably 0.001% by weight or less, and even more preferably is 0.0005% by weight or less.
更に、本発明の外用組成物は、前述する成分の他に、薬学的又は香粧学的な生理機能を発揮できる薬効成分が、必要に応じて含まれていてもよい。このような薬効成分としては、例えば、ステロイド剤（デキサメタゾン、塩酸デキサメタゾン、酢酸デキサメタゾン、塩酸ヒドロコルチゾン、吉草酸プレドニゾロン、酢酸プレドニゾロン等）、抗ヒスタミン剤（ジフェンヒドラミン、塩酸ジフェンヒドラミン、マレイン酸クロルフェニラミン等）、局所麻酔剤（リドカイン、ジブカイン、プロカイン、テトラカイン、ブピバカイン、メピバカイン、クロロプロカイン、プロパラカイン、メプリルカイン又はこれらの塩）、安息香酸アルキルエステル（例えばアミノ安息香酸エチル、塩酸パラブチルアミノ安息香酸ジエチルアミノエチル）、オルソカイン、オキセサゼイン、オキシポリエントキシデカン、ロートエキス、ペルカミンパーゼ、テシットデシチン等）、抗炎症剤（アラントイン、サリチル酸、サリチル酸グリコール、サリチル酸メチル、インドメタシン、フェルビナク、ジクロフェナクナトリウム、ロキソプロフェンナトリウム等）、殺菌剤（イソプロピルメチルフェノール、塩化ベンザルコニウム、塩化デカリニウム、塩化ベンゼトニウム、塩化セチルピリジニウム、塩酸クロルヘキシジン、グルコン酸クロルヘキシジン、アンモニア水、スルファジアジン、乳酸、フェノール等）、鎮痒剤（クロタミトン、チアントール等）、皮膚保護剤（コロジオン、ヒマシ油等）、血行促進成分（ノニル酸ワニリルアミド、ニコチン酸ベンジルエステル、カプサイシン、トウガラシエキス等）、ビタミン類（ビタミンＡ，Ｂ，Ｃ，Ｄ，Ｅ等）、ムコ多糖類（コンドロイチン硫酸ナトリウム、グルコサミン、ヒアルロン酸等）等が挙げられる。これらの薬効成分は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、本発明の外用組成物において、これらの薬効成分を含有させる場合、その含有量については、使用する薬効成分の種類、期待する効果等に応じて適宜設定すればよい。 Furthermore, in addition to the above-mentioned components, the external composition of the present invention may optionally contain medicinal components capable of exerting pharmaceutical or cosmetic physiological functions. Such medicinal ingredients include, for example, steroids (dexamethasone, dexamethasone hydrochloride, dexamethasone acetate, hydrocortisone hydrochloride, prednisolone valerate, prednisolone acetate, etc.), antihistamines (diphenhydramine, diphenhydramine hydrochloride, chlorpheniramine maleate, etc.), and local anesthesia. agents (lidocaine, dibucaine, procaine, tetracaine, bupivacaine, mepivacaine, chloroprocaine, proparacaine, meprilcaine or salts thereof), benzoic acid alkyl esters (e.g. ethyl aminobenzoate, diethylaminoethyl parabutylaminobenzoate hydrochloride), orthocaine, oxesazein, oxypolyentoxydecane, rotoextract, percaminpase, tesitdesitin, etc.), anti-inflammatory agents (allantoin, salicylic acid, glycol salicylate, methyl salicylate, indomethacin, felbinac, diclofenac sodium, loxoprofen sodium, etc.), bactericidal agents (isopropylmethylphenol, chloride, etc.) benzalkonium, dequalinium chloride, benzethonium chloride, cetylpyridinium chloride, chlorhexidine hydrochloride, chlorhexidine gluconate, aqueous ammonia, sulfadiazine, lactic acid, phenol, etc.), antipruritics (crotamiton, thianthol, etc.), skin protectants (collodion, castor oil, etc.) ), blood circulation promoting ingredients (nonylic acid vanillylamide, nicotinic acid benzyl ester, capsaicin, hot pepper extract, etc.), vitamins (vitamins A, B, C, D, E, etc.), mucopolysaccharides (sodium chondroitin sulfate, glucosamine, hyaluronic acid) etc.) etc. These medicinal ingredients may be used alone or in combination of two or more. Furthermore, when the external composition of the present invention contains these medicinal ingredients, the content may be appropriately set depending on the type of medicinal ingredient used, the expected effect, etc.
製剤形態・用途
本発明の外用組成物がとりうる製剤形態としては、水相と油相とを含んでいれば特に限定されず、例えば、水中油滴分散型（乳化型ではない）、油中水滴分散型（乳化型ではない）、水中油乳化型、及び油中水乳化型が挙げられる。本発明の外用組成物は、分散化効果に優れているため、水を多く含む製剤形態であっても、効果的に分散化効果を得ることができる。このような観点から、本発明の外用組成物がとりうる製剤形態の好ましい例としては、水中油滴分散型（乳化型ではない）、及び水中油乳化型が挙げられる。更に、本発明の外用組成物は、分散化効果に優れているため、界面活性剤を含まなくても効果的に分散化効果を得ることができる。このような観点から、本発明の外用組成物がとりうる製剤形態の好ましい例としては、水中油滴分散型（乳化型ではない）が挙げられる。
Formulation/Application The external composition of the present invention may take any form as long as it contains an aqueous phase and an oil phase. Examples include water droplet dispersion type (not emulsion type), oil-in-water emulsion type, and water-in-oil emulsion type. Since the external composition of the present invention has an excellent dispersion effect, it is possible to effectively obtain a dispersion effect even in a formulation containing a large amount of water. From this point of view, preferred examples of the formulation form that the external composition of the present invention can take include an oil-in-water dispersion type (not an emulsion type) and an oil-in-water emulsion type. Furthermore, since the external composition of the present invention has an excellent dispersing effect, it is possible to effectively obtain the dispersing effect even without containing a surfactant. From this point of view, a preferred example of the formulation form that the external composition of the present invention can take is an oil-in-water dispersion type (not an emulsion type).
本発明の外用組成物は、化粧料、外用医薬部外品、外用医薬品等の外用剤として使用することができる。本発明の外用組成物の製品形態については、特に制限されないが、例えば、ローション剤、クリーム剤、軟膏剤、乳液剤、ゲル剤、油剤、リニメント剤、エアゾール剤等が挙げられる。 The external composition of the present invention can be used as external preparations such as cosmetics, external quasi-drugs, and external medicines. The product form of the external composition of the present invention is not particularly limited, but examples thereof include lotions, creams, ointments, emulsions, gels, oils, liniments, aerosols, and the like.
製造方法
本発明の外用組成物は、製剤形態に応じて、公知の外用組成物の製剤化手法に従って製造することができる。例えば、本発明の外用組成物の製造方法としては、含有させる成分を水溶性成分と油性成分に分けて、水溶性成分を含む水相と、油性成分を含む油相とを調製し、これらを公知の分散手法により製剤化する方法が挙げられる。
Manufacturing method The external composition of the present invention can be manufactured according to known formulation methods for external compositions, depending on the formulation form. For example, as a method for producing the external composition of the present invention, the components to be contained are divided into water-soluble components and oil-based components, and an aqueous phase containing the water-soluble components and an oil phase containing the oil-based components are prepared. Examples include methods of formulating formulations using known dispersion techniques.
２．分散化方法
上述するように、Ｎ－メチル－２－ピロリドンは、ウフェナマート、液状炭化水素、及び水を有する外用組成物を分散化する。従って、本発明は、更に、（Ａ）ウフェナマート、（Ｃ）液状炭化水素、及び（Ｄ）水を有する外用組成物において、（Ｂ）Ｎ－メチル－２－ピロリドンを配合する、外用組成物の分散化方法を提供する。
2. Dispersion Method As mentioned above, N-methyl-2-pyrrolidone disperses a topical composition having ufenamate, a liquid hydrocarbon, and water. Therefore, the present invention further provides an external composition comprising (A) ufenamate, (C) a liquid hydrocarbon, and (D) water, which contains (B) N-methyl-2-pyrrolidone. Provide a decentralization method.
本発明の分散化方法において、分散化とは、外用組成物に用いられる水相と油相とが、界面活性剤が配合されていない条件で撹拌し、放置後にも分散状態を維持することをいう。分散状態とは、少なくとも、ほとんど（わずかな分離を許容する意である）が分散状態であることをいい、好ましくは、分離が認められず目視可能な（直径０．１～１．０ｍｍ）液滴が分散している状態であることをいい、より好ましくは、分離が認められず目視できない微小な（直径０．１ｍｍ未満）液滴が分散している状態をいう。 In the dispersion method of the present invention, dispersion means that the aqueous phase and oil phase used in the external composition are stirred under conditions where no surfactant is mixed and maintain a dispersed state even after standing. say. A dispersed state refers to a state in which at least most of the liquid (with a slight separation is allowed) is dispersed, and preferably a liquid in which no separation is observed and is visible (0.1 to 1.0 mm in diameter). It refers to a state in which droplets are dispersed, and more preferably a state in which minute droplets (less than 0.1 mm in diameter) that are not separated and cannot be seen with the naked eye are dispersed.
本発明の分散化方法において、使用する各成分の種類や含有量、外用組成物に配合される成分の種類や含有量、及び製剤形態等については、前記「１．外用組成物」の場合と同様である。 In the dispersion method of the present invention, the types and contents of each ingredient used, the types and contents of ingredients added to the external composition, and the formulation form are the same as in the case of "1. External composition" above. The same is true.
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 EXAMPLES The present invention will be explained in more detail with reference to Examples below, but the present invention is not limited thereto.
試験例
表２に示す外用組成物（水中油滴分散液）を調製した。具体的には、ウフェナマートと流動パラフィンとを均一になるまで混和して油性液を得て、油性液に他の成分を添加して均一になるまで混和し、最後に合計が１００重量％となるように精製水を添加し、均一になるまで攪拌した。
Test Example An external composition (oil-in-water dispersion) shown in Table 2 was prepared. Specifically, ufenamate and liquid paraffin are mixed until homogeneous to obtain an oily liquid, and other components are added to the oily liquid and mixed until homogeneous, and finally the total becomes 100% by weight. Add purified water and stir until homogeneous.
調製した外用組成物を、室温条件下で１０分間静置した後の分散状態を、以下の基準に基づいて評価した。以下の基準において、分離とは、分散していた液滴（油滴）の少なくとも一部が分散できなくなり底に沈む現象をいい、その中でも、液滴（油滴）の全てが底に沈む現象を完全に分離した状態という。また、各評価基準の代表写真を表１に示し、評価結果を表２に示す。 The prepared composition for external use was allowed to stand for 10 minutes at room temperature, and then the dispersion state was evaluated based on the following criteria. In the following criteria, separation refers to the phenomenon in which at least part of the dispersed droplets (oil droplets) become unable to disperse and sink to the bottom, and among these, the phenomenon in which all of the droplets (oil droplets) sink to the bottom. is said to be completely separated. Further, representative photographs of each evaluation criterion are shown in Table 1, and evaluation results are shown in Table 2.
◎：分離が認められず、目視できない微小な液滴（油滴）が分散している。
○：分離が認められず、目視可能な液滴（油滴）が分散している。
△：わずかな分離のみで、液滴（油滴）の分散状態が維持されている。
×：分離の程度が大きく、液滴（油滴）の分散状態がほとんど維持されていない。
××：完全に分離した。
◎: No separation was observed, and minute droplets (oil droplets) that were invisible to the naked eye were dispersed.
○: No separation was observed, and visible droplets (oil droplets) were dispersed.
Δ: The dispersed state of the droplets (oil droplets) is maintained with only slight separation.
×: The degree of separation is large, and the dispersed state of the droplets (oil droplets) is hardly maintained.
XX: Completely separated.
比較例１に示すように、ウフェナマートを含む外用組成物は、流動パラフィンの油相と水相とが混ざらない。これに対し、実施例１～４に示されるように、Ｎ－メチル－２－ピロリドンを配合することで、優れた分散性が得られた。なお、比較例２～６に示すように、Ｎ－メチル－２－ピロリドンと同様に、水溶性で極性が高い点で共通する成分である、プロピレングリコール、ジプロピレングリコール、１，３－ブチレングリコール、又はグリセリンを配合した場合には、分散効果は得られなかった。つまり、実施例１～４で認められる分散効果は、Ｎ－メチル－２－ピロリドンに特有の効果であることがわかった。 As shown in Comparative Example 1, in the external composition containing ufenamate, the oil phase and water phase of liquid paraffin do not mix. On the other hand, as shown in Examples 1 to 4, excellent dispersibility was obtained by blending N-methyl-2-pyrrolidone. As shown in Comparative Examples 2 to 6, similar to N-methyl-2-pyrrolidone, propylene glycol, dipropylene glycol, and 1,3-butylene glycol are common components in that they are water-soluble and highly polar. , or when glycerin was blended, no dispersion effect was obtained. In other words, it was found that the dispersion effect observed in Examples 1 to 4 was an effect unique to N-methyl-2-pyrrolidone.
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