JP2024055826A - Loxoprofen or salt thereof and pharmaceutical composition containing salicylic acid - Google Patents
Loxoprofen or salt thereof and pharmaceutical composition containing salicylic acid Download PDFInfo
- Publication number
- JP2024055826A JP2024055826A JP2023173304A JP2023173304A JP2024055826A JP 2024055826 A JP2024055826 A JP 2024055826A JP 2023173304 A JP2023173304 A JP 2023173304A JP 2023173304 A JP2023173304 A JP 2023173304A JP 2024055826 A JP2024055826 A JP 2024055826A
- Authority
- JP
- Japan
- Prior art keywords
- pharmaceutical composition
- mass
- loxoprofen
- oil
- acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 93
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 title claims abstract description 78
- 229960002373 loxoprofen Drugs 0.000 title claims abstract description 77
- 150000003839 salts Chemical class 0.000 title claims abstract description 65
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 title claims abstract description 46
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 229960004889 salicylic acid Drugs 0.000 title claims abstract description 23
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 26
- 150000003870 salicylic acids Chemical class 0.000 claims description 21
- 239000007788 liquid Substances 0.000 claims description 18
- 239000002552 dosage form Substances 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000002674 ointment Substances 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000007921 spray Substances 0.000 claims description 5
- 239000006071 cream Substances 0.000 claims description 3
- 150000003873 salicylate salts Chemical class 0.000 claims description 3
- -1 alkali metal salts Chemical class 0.000 description 83
- 235000002639 sodium chloride Nutrition 0.000 description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 235000019441 ethanol Nutrition 0.000 description 38
- LVYLCBNXHHHPSB-UHFFFAOYSA-N 2-hydroxyethyl salicylate Chemical compound OCCOC(=O)C1=CC=CC=C1O LVYLCBNXHHHPSB-UHFFFAOYSA-N 0.000 description 28
- 235000014113 dietary fatty acids Nutrition 0.000 description 23
- 239000000194 fatty acid Substances 0.000 description 23
- 229930195729 fatty acid Natural products 0.000 description 23
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 17
- 235000008534 Capsicum annuum var annuum Nutrition 0.000 description 16
- 239000000126 substance Substances 0.000 description 16
- 150000005846 sugar alcohols Polymers 0.000 description 16
- 235000007586 terpenes Nutrition 0.000 description 16
- 235000002568 Capsicum frutescens Nutrition 0.000 description 15
- 241001247145 Sebastes goodei Species 0.000 description 15
- 229960002389 glycol salicylate Drugs 0.000 description 14
- 241000411851 herbal medicine Species 0.000 description 14
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 13
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 206010030113 Oedema Diseases 0.000 description 11
- 239000002202 Polyethylene glycol Substances 0.000 description 11
- 229920001223 polyethylene glycol Polymers 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 150000003505 terpenes Chemical class 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
- 150000001298 alcohols Chemical class 0.000 description 10
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 10
- 235000019410 glycyrrhizin Nutrition 0.000 description 10
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000000499 gel Substances 0.000 description 9
- 235000001968 nicotinic acid Nutrition 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229920006322 acrylamide copolymer Polymers 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 8
- OMNKZBIFPJNNIO-UHFFFAOYSA-N n-(2-methyl-4-oxopentan-2-yl)prop-2-enamide Chemical compound CC(=O)CC(C)(C)NC(=O)C=C OMNKZBIFPJNNIO-UHFFFAOYSA-N 0.000 description 8
- RGOVYLWUIBMPGK-UHFFFAOYSA-N nonivamide Chemical compound CCCCCCCCC(=O)NCC1=CC=C(O)C(OC)=C1 RGOVYLWUIBMPGK-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 7
- 239000004359 castor oil Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 229920001577 copolymer Polymers 0.000 description 7
- 239000011732 tocopherol Substances 0.000 description 7
- 229930003799 tocopherol Natural products 0.000 description 7
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 7
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 7
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 6
- 244000303040 Glycyrrhiza glabra Species 0.000 description 6
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 6
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000005215 alkyl ethers Chemical class 0.000 description 6
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 description 6
- 239000000679 carrageenan Substances 0.000 description 6
- 229920001525 carrageenan Polymers 0.000 description 6
- 229940113118 carrageenan Drugs 0.000 description 6
- 235000019438 castor oil Nutrition 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 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 6
- 150000004040 pyrrolidinones Chemical class 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 6
- GOXQRTZXKQZDDN-UHFFFAOYSA-N 2-Ethylhexyl acrylate Chemical compound CCCCC(CC)COC(=O)C=C GOXQRTZXKQZDDN-UHFFFAOYSA-N 0.000 description 5
- 235000002566 Capsicum Nutrition 0.000 description 5
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 5
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 235000010418 carrageenan Nutrition 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 235000014655 lactic acid Nutrition 0.000 description 5
- 239000004310 lactic acid Substances 0.000 description 5
- 229940010454 licorice Drugs 0.000 description 5
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 150000002814 niacins Chemical class 0.000 description 5
- 235000019477 peppermint oil Nutrition 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 5
- 229920005989 resin Polymers 0.000 description 5
- 239000011347 resin Substances 0.000 description 5
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 5
- 229940098465 tincture Drugs 0.000 description 5
- 229960000401 tranexamic acid Drugs 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- 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 5
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 4
- 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 4
- 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 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 240000008574 Capsicum frutescens Species 0.000 description 4
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 4
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 4
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000000853 adhesive Substances 0.000 description 4
- 230000001070 adhesive effect Effects 0.000 description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 4
- 150000003863 ammonium salts Chemical class 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 239000000730 antalgic agent Substances 0.000 description 4
- 230000001754 anti-pyretic effect Effects 0.000 description 4
- 239000002221 antipyretic Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 235000017663 capsaicin Nutrition 0.000 description 4
- 229960002504 capsaicin Drugs 0.000 description 4
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 4
- 229940043276 diisopropanolamine Drugs 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000010642 eucalyptus oil Substances 0.000 description 4
- 229940044949 eucalyptus oil Drugs 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 210000001156 gastric mucosa Anatomy 0.000 description 4
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 4
- 239000001685 glycyrrhizic acid Substances 0.000 description 4
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 4
- 229960004949 glycyrrhizic acid Drugs 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 229910017053 inorganic salt Inorganic materials 0.000 description 4
- 239000002563 ionic surfactant Substances 0.000 description 4
- 239000001630 malic acid Substances 0.000 description 4
- 235000011090 malic acid Nutrition 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 229960001047 methyl salicylate Drugs 0.000 description 4
- 239000011664 nicotinic acid Substances 0.000 description 4
- 239000002736 nonionic surfactant Substances 0.000 description 4
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 4
- 229960004063 propylene glycol Drugs 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000008247 solid mixture Substances 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- 239000002562 thickening agent Substances 0.000 description 4
- 235000019149 tocopherols Nutrition 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 3
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 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 3
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 3
- 239000004166 Lanolin Substances 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- 239000005844 Thymol Substances 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 229940087168 alpha tocopherol Drugs 0.000 description 3
- RZFHLOLGZPDCHJ-DLQZEEBKSA-N alpha-Tocotrienol Natural products Oc1c(C)c(C)c2O[C@@](CC/C=C(/CC/C=C(\CC/C=C(\C)/C)/C)\C)(C)CCc2c1C RZFHLOLGZPDCHJ-DLQZEEBKSA-N 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 229950004580 benzyl nicotinate Drugs 0.000 description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 229960000520 diphenhydramine Drugs 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 229920001971 elastomer Polymers 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 3
- 210000000548 hind-foot Anatomy 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 229920003049 isoprene rubber Polymers 0.000 description 3
- 235000019388 lanolin Nutrition 0.000 description 3
- 229940039717 lanolin Drugs 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 229960003511 macrogol Drugs 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229960003512 nicotinic acid Drugs 0.000 description 3
- 229940116257 pepper extract Drugs 0.000 description 3
- 229920001195 polyisoprene Polymers 0.000 description 3
- 159000000001 potassium salts Chemical class 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 239000010734 process oil Substances 0.000 description 3
- 239000005060 rubber Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229940083542 sodium Drugs 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 229960002920 sorbitol Drugs 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 229960000790 thymol Drugs 0.000 description 3
- 229960000984 tocofersolan Drugs 0.000 description 3
- 235000010384 tocopherol Nutrition 0.000 description 3
- 229960001295 tocopherol Drugs 0.000 description 3
- 229940042585 tocopherol acetate Drugs 0.000 description 3
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 3
- 239000000341 volatile oil Substances 0.000 description 3
- 239000002076 α-tocopherol Substances 0.000 description 3
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 2
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 2
- MOQGCGNUWBPGTQ-UHFFFAOYSA-N 2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde Chemical compound CC1=C(C=O)C(C)(C)CCC1 MOQGCGNUWBPGTQ-UHFFFAOYSA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- WDQMWEYDKDCEHT-UHFFFAOYSA-N 2-ethylhexyl 2-methylprop-2-enoate Chemical compound CCCCC(CC)COC(=O)C(C)=C WDQMWEYDKDCEHT-UHFFFAOYSA-N 0.000 description 2
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 2
- GJJVAFUKOBZPCB-UHFFFAOYSA-N 2-methyl-2-(4,8,12-trimethyltrideca-3,7,11-trienyl)-3,4-dihydrochromen-6-ol Chemical compound OC1=CC=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 GJJVAFUKOBZPCB-UHFFFAOYSA-N 0.000 description 2
- OTXNTMVVOOBZCV-UHFFFAOYSA-N 2R-gamma-tocotrienol Natural products OC1=C(C)C(C)=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 OTXNTMVVOOBZCV-UHFFFAOYSA-N 0.000 description 2
- XCNCWOPROFTLGU-RBKKPWLPSA-N 3-(L-Menthoxy)-2-methylpropane-1,2-diol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OCC(C)(O)CO XCNCWOPROFTLGU-RBKKPWLPSA-N 0.000 description 2
- MDVYIGJINBYKOM-IBSWDFHHSA-N 3-[(1r,2s,5r)-5-methyl-2-propan-2-ylcyclohexyl]oxypropane-1,2-diol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OCC(O)CO MDVYIGJINBYKOM-IBSWDFHHSA-N 0.000 description 2
- MDVYIGJINBYKOM-UHFFFAOYSA-N 3-[[5-Methyl-2-(1-methylethyl)cyclohexyl]oxy]-1,2-propanediol Chemical compound CC(C)C1CCC(C)CC1OCC(O)CO MDVYIGJINBYKOM-UHFFFAOYSA-N 0.000 description 2
- GNSFRPWPOGYVLO-UHFFFAOYSA-N 3-hydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCO GNSFRPWPOGYVLO-UHFFFAOYSA-N 0.000 description 2
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 2
- ODHCTXKNWHHXJC-UHFFFAOYSA-N 5-oxoproline Chemical compound OC(=O)C1CCC(=O)N1 ODHCTXKNWHHXJC-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- 102000005751 Alcohol Oxidoreductases Human genes 0.000 description 2
- 108010031132 Alcohol Oxidoreductases Proteins 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 241000208983 Arnica Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-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
- 240000004160 Capsicum annuum Species 0.000 description 2
- BAVONGHXFVOKBV-UHFFFAOYSA-N Carveol Chemical compound CC(=C)C1CC=C(C)C(O)C1 BAVONGHXFVOKBV-UHFFFAOYSA-N 0.000 description 2
- 240000003538 Chamaemelum nobile Species 0.000 description 2
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 2
- 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 2
- 241000723346 Cinnamomum camphora Species 0.000 description 2
- 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 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 2
- GYCKQBWUSACYIF-UHFFFAOYSA-N Ethyl salicylate Chemical compound CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 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 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 244000241838 Lycium barbarum Species 0.000 description 2
- 235000015459 Lycium barbarum Nutrition 0.000 description 2
- 235000015468 Lycium chinense Nutrition 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 244000170916 Paeonia officinalis Species 0.000 description 2
- 235000006484 Paeonia officinalis Nutrition 0.000 description 2
- 244000124853 Perilla frutescens Species 0.000 description 2
- AEVLWICMAHGAMS-UHFFFAOYSA-N Phellandral Chemical compound CC(C)C1CCC(C=O)=CC1 AEVLWICMAHGAMS-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002367 Polyisobutene Polymers 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 244000184734 Pyrus japonica Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- MOYAFQVGZZPNRA-UHFFFAOYSA-N Terpinolene Chemical compound CC(C)=C1CCC(C)=CC1 MOYAFQVGZZPNRA-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- CGQCWMIAEPEHNQ-UHFFFAOYSA-N Vanillylmandelic acid Chemical compound COC1=CC(C(O)C(O)=O)=CC=C1O CGQCWMIAEPEHNQ-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 229940048053 acrylate Drugs 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229940064063 alpha tocotrienol Drugs 0.000 description 2
- XCPQUQHBVVXMRQ-UHFFFAOYSA-N alpha-Fenchene Natural products C1CC2C(=C)CC1C2(C)C XCPQUQHBVVXMRQ-UHFFFAOYSA-N 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- 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 2
- 229960001950 benzethonium chloride Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- UAHWPYUMFXYFJY-UHFFFAOYSA-N beta-myrcene Chemical compound CC(C)=CCCC(=C)C=C UAHWPYUMFXYFJY-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 2
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical compound OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- CRPUJAZIXJMDBK-UHFFFAOYSA-N camphene Chemical compound C1CC2C(=C)C(C)(C)C1C2 CRPUJAZIXJMDBK-UHFFFAOYSA-N 0.000 description 2
- 229930008380 camphor Natural products 0.000 description 2
- 229960000846 camphor Drugs 0.000 description 2
- ULDHMXUKGWMISQ-UHFFFAOYSA-N carvone Chemical compound CC(=C)C1CC=C(C)C(=O)C1 ULDHMXUKGWMISQ-UHFFFAOYSA-N 0.000 description 2
- 239000010628 chamomile oil Substances 0.000 description 2
- 229940046978 chlorpheniramine maleate Drugs 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- NEHNMFOYXAPHSD-UHFFFAOYSA-N citronellal Chemical compound O=CCC(C)CCC=C(C)C NEHNMFOYXAPHSD-UHFFFAOYSA-N 0.000 description 2
- GJWSUKYXUMVMGX-UHFFFAOYSA-N citronellic acid Chemical compound OC(=O)CC(C)CCC=C(C)C GJWSUKYXUMVMGX-UHFFFAOYSA-N 0.000 description 2
- QMVPMAAFGQKVCJ-UHFFFAOYSA-N citronellol Chemical compound OCCC(C)CCC=C(C)C QMVPMAAFGQKVCJ-UHFFFAOYSA-N 0.000 description 2
- 229920006026 co-polymeric resin Polymers 0.000 description 2
- 239000002826 coolant Substances 0.000 description 2
- 239000003431 cross linking reagent Substances 0.000 description 2
- DNTGGZPQPQTDQF-XBXARRHUSA-N crotamiton Chemical compound C/C=C/C(=O)N(CC)C1=CC=CC=C1C DNTGGZPQPQTDQF-XBXARRHUSA-N 0.000 description 2
- 229960003338 crotamiton Drugs 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- 229940031578 diisopropyl adipate Drugs 0.000 description 2
- 229940031569 diisopropyl sebacate Drugs 0.000 description 2
- XFKBBSZEQRFVSL-UHFFFAOYSA-N dipropan-2-yl decanedioate Chemical compound CC(C)OC(=O)CCCCCCCCC(=O)OC(C)C XFKBBSZEQRFVSL-UHFFFAOYSA-N 0.000 description 2
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 2
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229960003720 enoxolone Drugs 0.000 description 2
- 229940005667 ethyl salicylate Drugs 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 229940014259 gelatin Drugs 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- ZYTMANIQRDEHIO-KXUCPTDWSA-N isopulegol Chemical compound C[C@@H]1CC[C@@H](C(C)=C)[C@H](O)C1 ZYTMANIQRDEHIO-KXUCPTDWSA-N 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- CDOSHBSSFJOMGT-UHFFFAOYSA-N linalool Chemical compound CC(C)=CCCC(C)(O)C=C CDOSHBSSFJOMGT-UHFFFAOYSA-N 0.000 description 2
- HOVAGTYPODGVJG-UHFFFAOYSA-N methyl beta-galactoside Natural products COC1OC(CO)C(O)C(O)C1O HOVAGTYPODGVJG-UHFFFAOYSA-N 0.000 description 2
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 2
- 230000003020 moisturizing effect Effects 0.000 description 2
- JXTPJDDICSTXJX-UHFFFAOYSA-N n-Triacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCC JXTPJDDICSTXJX-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
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 229940056211 paraffin Drugs 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- NDTYTMIUWGWIMO-UHFFFAOYSA-N perillyl alcohol Chemical compound CC(=C)C1CCC(CO)=CC1 NDTYTMIUWGWIMO-UHFFFAOYSA-N 0.000 description 2
- RUMOYJJNUMEFDD-UHFFFAOYSA-N perillyl aldehyde Chemical compound CC(=C)C1CCC(C=O)=CC1 RUMOYJJNUMEFDD-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- HKZQJZIFODOLFR-UHFFFAOYSA-N piperitenone Chemical compound CC(C)=C1CCC(C)=CC1=O HKZQJZIFODOLFR-UHFFFAOYSA-N 0.000 description 2
- 239000004584 polyacrylic acid Substances 0.000 description 2
- 229920001083 polybutene Polymers 0.000 description 2
- 229920000346 polystyrene-polyisoprene block-polystyrene Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- 229940068984 polyvinyl alcohol Drugs 0.000 description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- NDVASEGYNIMXJL-UHFFFAOYSA-N sabinene Chemical compound C=C1CCC2(C(C)C)C1C2 NDVASEGYNIMXJL-UHFFFAOYSA-N 0.000 description 2
- SGAWOGXMMPSZPB-UHFFFAOYSA-N safranal Chemical compound CC1=C(C=O)C(C)(C)CC=C1 SGAWOGXMMPSZPB-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229920002545 silicone oil Polymers 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 229940080236 sodium cetyl sulfate Drugs 0.000 description 2
- 229940037001 sodium edetate Drugs 0.000 description 2
- CRPCXAMJWCDHFM-UHFFFAOYSA-M sodium;5-oxopyrrolidine-2-carboxylate Chemical compound [Na+].[O-]C(=O)C1CCC(=O)N1 CRPCXAMJWCDHFM-UHFFFAOYSA-M 0.000 description 2
- GGHPAKFFUZUEKL-UHFFFAOYSA-M sodium;hexadecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCCCOS([O-])(=O)=O GGHPAKFFUZUEKL-UHFFFAOYSA-M 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 230000007480 spreading Effects 0.000 description 2
- 238000003892 spreading Methods 0.000 description 2
- 229940032094 squalane Drugs 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 229920003048 styrene butadiene rubber Polymers 0.000 description 2
- 229920000468 styrene butadiene styrene block copolymer Polymers 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
- 229920003051 synthetic elastomer Polymers 0.000 description 2
- 239000005061 synthetic rubber Substances 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- DZVXRFMREAADPP-UHFFFAOYSA-N thujyl alcohol Chemical compound CC1C(O)CC2(C(C)C)C1C2 DZVXRFMREAADPP-UHFFFAOYSA-N 0.000 description 2
- 229930003802 tocotrienol Natural products 0.000 description 2
- 239000011731 tocotrienol Substances 0.000 description 2
- 235000019148 tocotrienols Nutrition 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- SKBXVAOMEVOTGJ-UHFFFAOYSA-N xi-Pinol Chemical compound CC1=CCC2C(C)(C)OC1C2 SKBXVAOMEVOTGJ-UHFFFAOYSA-N 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- RZFHLOLGZPDCHJ-XZXLULOTSA-N α-Tocotrienol Chemical compound OC1=C(C)C(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1C RZFHLOLGZPDCHJ-XZXLULOTSA-N 0.000 description 2
- 235000004835 α-tocopherol Nutrition 0.000 description 2
- 235000019145 α-tocotrienol Nutrition 0.000 description 2
- 239000011730 α-tocotrienol Substances 0.000 description 2
- WGVKWNUPNGFDFJ-DQCZWYHMSA-N β-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C WGVKWNUPNGFDFJ-DQCZWYHMSA-N 0.000 description 2
- GZIFEOYASATJEH-VHFRWLAGSA-N δ-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-VHFRWLAGSA-N 0.000 description 2
- NFLGAXVYCFJBMK-RKDXNWHRSA-N (+)-isomenthone Natural products CC(C)[C@H]1CC[C@@H](C)CC1=O NFLGAXVYCFJBMK-RKDXNWHRSA-N 0.000 description 1
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- NDVASEGYNIMXJL-NXEZZACHSA-N (+)-sabinene Natural products C=C1CC[C@@]2(C(C)C)[C@@H]1C2 NDVASEGYNIMXJL-NXEZZACHSA-N 0.000 description 1
- 229930006727 (-)-endo-fenchol Natural products 0.000 description 1
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 1
- 229930007631 (-)-perillyl alcohol Natural products 0.000 description 1
- BAVONGHXFVOKBV-ZJUUUORDSA-N (-)-trans-carveol Natural products CC(=C)[C@@H]1CC=C(C)[C@@H](O)C1 BAVONGHXFVOKBV-ZJUUUORDSA-N 0.000 description 1
- 239000001871 (1R,2R,5S)-5-methyl-2-prop-1-en-2-ylcyclohexan-1-ol Substances 0.000 description 1
- 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
- 239000001490 (3R)-3,7-dimethylocta-1,6-dien-3-ol Substances 0.000 description 1
- REPVLJRCJUVQFA-MDVIFZSFSA-N (3r,4r)-4,6,6-trimethylbicyclo[3.1.1]heptan-3-ol Chemical compound C1[C@@H](O)[C@H](C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-MDVIFZSFSA-N 0.000 description 1
- JWQKMEKSFPNAIB-SNVBAGLBSA-N (5r)-1-methyl-5-prop-1-en-2-ylcyclohexene Chemical compound CC(=C)[C@@H]1CCC=C(C)C1 JWQKMEKSFPNAIB-SNVBAGLBSA-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
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- QMVPMAAFGQKVCJ-SNVBAGLBSA-N (R)-(+)-citronellol Natural products OCC[C@H](C)CCC=C(C)C QMVPMAAFGQKVCJ-SNVBAGLBSA-N 0.000 description 1
- FGYKUFVNYVMTAM-UHFFFAOYSA-N (R)-2,5,8-trimethyl-2-(4,8,12-trimethyl-trideca-3t,7t,11-trienyl)-chroman-6-ol Natural products OC1=CC(C)=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1C FGYKUFVNYVMTAM-UHFFFAOYSA-N 0.000 description 1
- CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 description 1
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- YHMYGUUIMTVXNW-UHFFFAOYSA-N 1,3-dihydrobenzimidazole-2-thione Chemical compound C1=CC=C2NC(S)=NC2=C1 YHMYGUUIMTVXNW-UHFFFAOYSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- 229940035437 1,3-propanediol Drugs 0.000 description 1
- VDPRSOCKHVPZRS-UHFFFAOYSA-N 1-(2-decylsulfanylethyl)pyrrolidin-2-one Chemical compound CCCCCCCCCCSCCN1CCCC1=O VDPRSOCKHVPZRS-UHFFFAOYSA-N 0.000 description 1
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- 239000001169 1-methyl-4-propan-2-ylcyclohexa-1,4-diene Substances 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
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- MUHFRORXWCGZGE-KTKRTIGZSA-N 2-hydroxyethyl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCCO MUHFRORXWCGZGE-KTKRTIGZSA-N 0.000 description 1
- ROGIWVXWXZRRMZ-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1 ROGIWVXWXZRRMZ-UHFFFAOYSA-N 0.000 description 1
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
- BGRXBNZMPMGLQI-UHFFFAOYSA-N 2-octyldodecyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCC(CCCCCCCC)CCCCCCCCCC BGRXBNZMPMGLQI-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ODADKLYLWWCHNB-UHFFFAOYSA-N 2R-delta-tocotrienol Natural products OC1=CC(C)=C2OC(CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1 ODADKLYLWWCHNB-UHFFFAOYSA-N 0.000 description 1
- CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 0.000 description 1
- USMNOWBWPHYOEA-UHFFFAOYSA-N 3‐isothujone Chemical compound CC1C(=O)CC2(C(C)C)C1C2 USMNOWBWPHYOEA-UHFFFAOYSA-N 0.000 description 1
- VLDFMKOUUQYFGF-UHFFFAOYSA-N 4-(butoxymethyl)-2-methoxyphenol Chemical compound CCCCOCC1=CC=C(O)C(OC)=C1 VLDFMKOUUQYFGF-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
- CUXGDKOCSSIRKK-UHFFFAOYSA-N 7-methyloctyl prop-2-enoate Chemical compound CC(C)CCCCCCOC(=O)C=C CUXGDKOCSSIRKK-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 241000332371 Abutilon x hybridum Species 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 241000157280 Aesculus hippocastanum Species 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241000218157 Aquilegia vulgaris Species 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000132012 Atractylodes Species 0.000 description 1
- 241000759834 Aucuba japonica Species 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- MOZDKDIOPSPTBH-UHFFFAOYSA-N Benzyl parahydroxybenzoate Chemical compound C1=CC(O)=CC=C1C(=O)OCC1=CC=CC=C1 MOZDKDIOPSPTBH-UHFFFAOYSA-N 0.000 description 1
- 206010004542 Bezoar Diseases 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 235000010893 Bischofia javanica Nutrition 0.000 description 1
- 240000005220 Bischofia javanica Species 0.000 description 1
- 235000011960 Brassica ruvo Nutrition 0.000 description 1
- 240000007436 Cananga odorata Species 0.000 description 1
- 235000008499 Canella winterana Nutrition 0.000 description 1
- 244000080208 Canella winterana Species 0.000 description 1
- 235000002567 Capsicum annuum Nutrition 0.000 description 1
- 244000284152 Carapichea ipecacuanha Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 235000005747 Carum carvi Nutrition 0.000 description 1
- 240000000467 Carum carvi Species 0.000 description 1
- 239000005973 Carvone Substances 0.000 description 1
- 244000037364 Cinnamomum aromaticum Species 0.000 description 1
- 235000014489 Cinnamomum aromaticum Nutrition 0.000 description 1
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229930008398 Citronellate Natural products 0.000 description 1
- 241000212948 Cnidium Species 0.000 description 1
- 244000077995 Coix lacryma jobi Species 0.000 description 1
- 241000037740 Coptis chinensis Species 0.000 description 1
- 241000218176 Corydalis Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 235000015655 Crocus sativus Nutrition 0.000 description 1
- 244000124209 Crocus sativus Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- 244000008991 Curcuma longa Species 0.000 description 1
- 235000003405 Curcuma zedoaria Nutrition 0.000 description 1
- 240000009138 Curcuma zedoaria Species 0.000 description 1
- 241001327300 Cymbopogon schoenanthus Species 0.000 description 1
- GZIFEOYASATJEH-UHFFFAOYSA-N D-delta tocopherol Natural products OC1=CC(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 GZIFEOYASATJEH-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- MQIUGAXCHLFZKX-UHFFFAOYSA-N Di-n-octyl phthalate Natural products CCCCCCCCOC(=O)C1=CC=CC=C1C(=O)OCCCCCCCC MQIUGAXCHLFZKX-UHFFFAOYSA-N 0.000 description 1
- VIZORQUEIQEFRT-UHFFFAOYSA-N Diethyl adipate Chemical compound CCOC(=O)CCCCC(=O)OCC VIZORQUEIQEFRT-UHFFFAOYSA-N 0.000 description 1
- RDOFJDLLWVCMRU-UHFFFAOYSA-N Diisobutyl adipate Chemical compound CC(C)COC(=O)CCCCC(=O)OCC(C)C RDOFJDLLWVCMRU-UHFFFAOYSA-N 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 1
- 240000002943 Elettaria cardamomum Species 0.000 description 1
- 241000402754 Erythranthe moschata Species 0.000 description 1
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 description 1
- IAIHUHQCLTYTSF-MRTMQBJTSA-N Fenchyl alcohol Chemical compound C1C[C@]2(C)[C@H](O)C(C)(C)[C@H]1C2 IAIHUHQCLTYTSF-MRTMQBJTSA-N 0.000 description 1
- 108010022355 Fibroins Proteins 0.000 description 1
- 240000006927 Foeniculum vulgare Species 0.000 description 1
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 1
- 241000605372 Fritillaria Species 0.000 description 1
- 241001071795 Gentiana Species 0.000 description 1
- 239000005792 Geraniol Substances 0.000 description 1
- GLZPCOQZEFWAFX-YFHOEESVSA-N Geraniol Natural products CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 description 1
- 241000208152 Geranium Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- GUIBJJJLGSYNKE-UHFFFAOYSA-N Hepronicate Chemical compound C=1C=CN=CC=1C(=O)OCC(COC(=O)C=1C=NC=CC=1)(CCCCCC)COC(=O)C1=CC=CN=C1 GUIBJJJLGSYNKE-UHFFFAOYSA-N 0.000 description 1
- CMBYOWLFQAFZCP-UHFFFAOYSA-N Hexyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCCCCC CMBYOWLFQAFZCP-UHFFFAOYSA-N 0.000 description 1
- 239000013032 Hydrocarbon resin Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 235000002710 Ilex cornuta Nutrition 0.000 description 1
- 241001310146 Ilex cornuta Species 0.000 description 1
- 239000009471 Ipecac Substances 0.000 description 1
- DTGKSKDOIYIVQL-MRTMQBJTSA-N Isoborneol Natural products C1C[C@@]2(C)[C@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-MRTMQBJTSA-N 0.000 description 1
- XPJVKCRENWUEJH-UHFFFAOYSA-N Isobutylparaben Chemical compound CC(C)COC(=O)C1=CC=C(O)C=C1 XPJVKCRENWUEJH-UHFFFAOYSA-N 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- CMHMMKSPYOOVGI-UHFFFAOYSA-N Isopropylparaben Chemical compound CC(C)OC(=O)C1=CC=C(O)C=C1 CMHMMKSPYOOVGI-UHFFFAOYSA-N 0.000 description 1
- 229940124091 Keratolytic Drugs 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 235000000072 L-ascorbyl-6-palmitate Nutrition 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 235000019501 Lemon oil Nutrition 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 241001071917 Lithospermum Species 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000218378 Magnolia Species 0.000 description 1
- 241001149162 Mallotus japonicus Species 0.000 description 1
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 1
- LMXFTMYMHGYJEI-UHFFFAOYSA-N Menthoglycol Natural products CC1CCC(C(C)(C)O)C(O)C1 LMXFTMYMHGYJEI-UHFFFAOYSA-N 0.000 description 1
- NFLGAXVYCFJBMK-UHFFFAOYSA-N Menthone Chemical compound CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 1
- XJLXINKUBYWONI-NNYOXOHSSA-N NADP zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-N 0.000 description 1
- GLZPCOQZEFWAFX-JXMROGBWSA-N Nerol Natural products CC(C)=CCC\C(C)=C\CO GLZPCOQZEFWAFX-JXMROGBWSA-N 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 235000010326 Osmanthus heterophyllus Nutrition 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000006002 Pepper Substances 0.000 description 1
- 235000004347 Perilla Nutrition 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 241000972673 Phellodendron amurense Species 0.000 description 1
- 241001522129 Pinellia Species 0.000 description 1
- 235000016761 Piper aduncum Nutrition 0.000 description 1
- 240000003889 Piper guineense Species 0.000 description 1
- 235000017804 Piper guineense Nutrition 0.000 description 1
- 235000008184 Piper nigrum Nutrition 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001219 Polysorbate 40 Polymers 0.000 description 1
- 229920002642 Polysorbate 65 Polymers 0.000 description 1
- 241001619461 Poria <basidiomycete fungus> Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- PXRCIOIWVGAZEP-UHFFFAOYSA-N Primaeres Camphenhydrat Natural products C1CC2C(O)(C)C(C)(C)C1C2 PXRCIOIWVGAZEP-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 description 1
- 235000009827 Prunus armeniaca Nutrition 0.000 description 1
- 244000018633 Prunus armeniaca Species 0.000 description 1
- 235000019484 Rapeseed oil Nutrition 0.000 description 1
- 235000017304 Ruaghas Nutrition 0.000 description 1
- 235000017089 Scutellaria baicalensis Nutrition 0.000 description 1
- 240000004534 Scutellaria baicalensis Species 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 241000208292 Solanaceae Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 239000002174 Styrene-butadiene Substances 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241001530209 Swertia Species 0.000 description 1
- UXZIDIYMFIBDKT-UHFFFAOYSA-N Sylvestrene Natural products CC(=C)C1CCCC(C)=C1 UXZIDIYMFIBDKT-UHFFFAOYSA-N 0.000 description 1
- 229920002253 Tannate Polymers 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
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-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
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 235000008853 Zanthoxylum piperitum Nutrition 0.000 description 1
- 244000131415 Zanthoxylum piperitum Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 229920006271 aliphatic hydrocarbon resin Polymers 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- HZVVJJIYJKGMFL-UHFFFAOYSA-N almasilate Chemical compound O.[Mg+2].[Al+3].[Al+3].O[Si](O)=O.O[Si](O)=O HZVVJJIYJKGMFL-UHFFFAOYSA-N 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- JZQOJFLIJNRDHK-CMDGGOBGSA-N alpha-irone Chemical compound CC1CC=C(C)C(\C=C\C(C)=O)C1(C)C JZQOJFLIJNRDHK-CMDGGOBGSA-N 0.000 description 1
- VYBREYKSZAROCT-UHFFFAOYSA-N alpha-myrcene Natural products CC(=C)CCCC(=C)C=C VYBREYKSZAROCT-UHFFFAOYSA-N 0.000 description 1
- WUOACPNHFRMFPN-UHFFFAOYSA-N alpha-terpineol Chemical compound CC1=CCC(C(C)(C)O)CC1 WUOACPNHFRMFPN-UHFFFAOYSA-N 0.000 description 1
- KQAZVFVOEIRWHN-UHFFFAOYSA-N alpha-thujene Natural products CC1=CCC2(C(C)C)C1C2 KQAZVFVOEIRWHN-UHFFFAOYSA-N 0.000 description 1
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- RJZNFXWQRHAVBP-UHFFFAOYSA-I aluminum;magnesium;pentahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Al+3] RJZNFXWQRHAVBP-UHFFFAOYSA-I 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229960004543 anhydrous citric acid Drugs 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 239000010617 anise oil Substances 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000010619 basil oil Substances 0.000 description 1
- 229940018006 basil oil Drugs 0.000 description 1
- 239000010620 bay oil Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229940092738 beeswax Drugs 0.000 description 1
- 229940116226 behenic acid Drugs 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
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- 235000021028 berry Nutrition 0.000 description 1
- 229940066595 beta tocopherol Drugs 0.000 description 1
- FGYKUFVNYVMTAM-YMCDKREISA-N beta-Tocotrienol Natural products Oc1c(C)c2c(c(C)c1)O[C@@](CC/C=C(\CC/C=C(\CC/C=C(\C)/C)/C)/C)(C)CC2 FGYKUFVNYVMTAM-YMCDKREISA-N 0.000 description 1
- JGQFVRIQXUFPAH-UHFFFAOYSA-N beta-citronellol Natural products OCCC(C)CCCC(C)=C JGQFVRIQXUFPAH-UHFFFAOYSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- BJQHLKABXJIVAM-UHFFFAOYSA-N bis(2-ethylhexyl) phthalate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1C(=O)OCC(CC)CCCC BJQHLKABXJIVAM-UHFFFAOYSA-N 0.000 description 1
- ATAJZVDXFMMOFG-UHFFFAOYSA-N bis(2-heptylundecyl) hexanedioate Chemical compound CCCCCCCCCC(CCCCCCC)COC(=O)CCCCC(=O)OCC(CCCCCCC)CCCCCCCCC ATAJZVDXFMMOFG-UHFFFAOYSA-N 0.000 description 1
- ZFMQKOWCDKKBIF-UHFFFAOYSA-N bis(3,5-difluorophenyl)phosphane Chemical compound FC1=CC(F)=CC(PC=2C=C(F)C=C(F)C=2)=C1 ZFMQKOWCDKKBIF-UHFFFAOYSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940116229 borneol Drugs 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- SWUIQEBPZIHZQS-UHFFFAOYSA-N calone Chemical compound O1CC(=O)COC2=CC(C)=CC=C21 SWUIQEBPZIHZQS-UHFFFAOYSA-N 0.000 description 1
- 239000010495 camellia oil Substances 0.000 description 1
- 229930006739 camphene Natural products 0.000 description 1
- ZYPYEBYNXWUCEA-UHFFFAOYSA-N camphenilone Natural products C1CC2C(=O)C(C)(C)C1C2 ZYPYEBYNXWUCEA-UHFFFAOYSA-N 0.000 description 1
- 239000010624 camphor oil Substances 0.000 description 1
- 229960000411 camphor oil Drugs 0.000 description 1
- 239000001772 cananga odorata hook. f. and thomas. oil Substances 0.000 description 1
- 239000001511 capsicum annuum Substances 0.000 description 1
- 229940007061 capsicum extract Drugs 0.000 description 1
- 239000001943 capsicum frutescens fruit extract Substances 0.000 description 1
- 239000001390 capsicum minimum Substances 0.000 description 1
- 229930006737 car-3-ene Natural products 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000005300 cardamomo Nutrition 0.000 description 1
- BQOFWKZOCNGFEC-UHFFFAOYSA-N carene Chemical compound C1C(C)=CCC2C(C)(C)C12 BQOFWKZOCNGFEC-UHFFFAOYSA-N 0.000 description 1
- 229930007796 carene Natural products 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 229940082483 carnauba wax Drugs 0.000 description 1
- 229930007646 carveol Natural products 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000007765 cera alba Substances 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- NFCRBQADEGXVDL-UHFFFAOYSA-M cetylpyridinium chloride monohydrate Chemical compound O.[Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 NFCRBQADEGXVDL-UHFFFAOYSA-M 0.000 description 1
- 235000019480 chamomile oil Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical class C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 1
- RFFOTVCVTJUTAD-UHFFFAOYSA-N cineole Natural products C1CC2(C)CCC1(C(C)C)O2 RFFOTVCVTJUTAD-UHFFFAOYSA-N 0.000 description 1
- 229960005233 cineole Drugs 0.000 description 1
- 229940017545 cinnamon bark Drugs 0.000 description 1
- 239000010630 cinnamon oil Substances 0.000 description 1
- 229940043350 citral Drugs 0.000 description 1
- 239000010632 citronella oil Substances 0.000 description 1
- 229930003633 citronellal Natural products 0.000 description 1
- 235000000983 citronellal Nutrition 0.000 description 1
- 235000000484 citronellol Nutrition 0.000 description 1
- 239000001279 citrus aurantifolia swingle expressed oil Substances 0.000 description 1
- 239000001111 citrus aurantium l. leaf oil Substances 0.000 description 1
- 239000001926 citrus aurantium l. subsp. bergamia wright et arn. oil Substances 0.000 description 1
- 239000001524 citrus aurantium oil Substances 0.000 description 1
- 239000001071 citrus reticulata blanco var. mandarin Substances 0.000 description 1
- 239000010634 clove oil Substances 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000010636 coriander oil Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 239000001812 curcuma zedoaria berg. rosc. Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000001941 cymbopogon citratus dc and cymbopogon flexuosus oil Substances 0.000 description 1
- 239000001939 cymbopogon martini roxb. stapf. oil Substances 0.000 description 1
- 229930007927 cymene Natural products 0.000 description 1
- SQIFACVGCPWBQZ-UHFFFAOYSA-N delta-terpineol Natural products CC(C)(O)C1CCC(=C)CC1 SQIFACVGCPWBQZ-UHFFFAOYSA-N 0.000 description 1
- 235000010389 delta-tocopherol Nutrition 0.000 description 1
- BTNBMQIHCRIGOU-UHFFFAOYSA-N delta-tocotrienol Natural products CC(=CCCC(=CCCC(=CCCOC1(C)CCc2cc(O)cc(C)c2O1)C)C)C BTNBMQIHCRIGOU-UHFFFAOYSA-N 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- JAUGGEIKQIHSMF-UHFFFAOYSA-N dialuminum;dimagnesium;dioxido(oxo)silane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O JAUGGEIKQIHSMF-UHFFFAOYSA-N 0.000 description 1
- NZZIMKJIVMHWJC-UHFFFAOYSA-N dibenzoylmethane Chemical class C=1C=CC=CC=1C(=O)CC(=O)C1=CC=CC=C1 NZZIMKJIVMHWJC-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940015826 dihydroxyaluminum aminoacetate Drugs 0.000 description 1
- 229940031769 diisobutyl adipate Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 description 1
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229960000735 docosanol Drugs 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
- 229940043264 dodecyl sulfate Drugs 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- FGYKUFVNYVMTAM-MUUNZHRXSA-N epsilon-Tocopherol Natural products OC1=CC(C)=C2O[C@@](CCC=C(C)CCC=C(C)CCC=C(C)C)(C)CCC2=C1C FGYKUFVNYVMTAM-MUUNZHRXSA-N 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- IAIHUHQCLTYTSF-UHFFFAOYSA-N fenchyl alcohol Natural products C1CC2(C)C(O)C(C)(C)C1C2 IAIHUHQCLTYTSF-UHFFFAOYSA-N 0.000 description 1
- 239000010643 fennel seed oil Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- OTXNTMVVOOBZCV-YMCDKREISA-N gamma-Tocotrienol Natural products Oc1c(C)c(C)c2O[C@@](CC/C=C(\CC/C=C(\CC/C=C(\C)/C)/C)/C)(C)CCc2c1 OTXNTMVVOOBZCV-YMCDKREISA-N 0.000 description 1
- 235000010382 gamma-tocopherol Nutrition 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
- 239000007789 gas Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 1
- 229940113087 geraniol Drugs 0.000 description 1
- 239000010648 geranium oil Substances 0.000 description 1
- 235000019717 geranium oil Nutrition 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 239000010649 ginger oil Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 235000010985 glycerol esters of wood rosin Nutrition 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 239000010651 grapefruit oil Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229950000262 hepronicate Drugs 0.000 description 1
- 229940100463 hexyl laurate Drugs 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 239000003906 humectant Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229920006270 hydrocarbon resin Polymers 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229960005436 inositol nicotinate Drugs 0.000 description 1
- 229930002839 ionone Natural products 0.000 description 1
- 150000002499 ionone derivatives Chemical class 0.000 description 1
- 229940029408 ipecac Drugs 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- SEZLYIWMVRUIKT-UHFFFAOYSA-N isopiperitenone Natural products CC(=C)C1CCC(C)=CC1=O SEZLYIWMVRUIKT-UHFFFAOYSA-N 0.000 description 1
- NFIDBGJMFKNGGQ-UHFFFAOYSA-N isopropylmethylphenol Natural products CC(C)CC1=CC=CC=C1O NFIDBGJMFKNGGQ-UHFFFAOYSA-N 0.000 description 1
- 229940095045 isopulegol Drugs 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 230000001530 keratinolytic effect Effects 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 239000000171 lavandula angustifolia l. flower oil Substances 0.000 description 1
- 239000010501 lemon oil Substances 0.000 description 1
- 235000001510 limonene Nutrition 0.000 description 1
- 229940087305 limonene Drugs 0.000 description 1
- 229930007744 linalool Natural products 0.000 description 1
- 235000011477 liquorice Nutrition 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 229960004211 loxoprofen sodium dihydrate Drugs 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001098 melissa officinalis l. leaf oil Substances 0.000 description 1
- 239000000457 mentha pulegium l. herb oil Substances 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229930007503 menthone Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 229930003658 monoterpene Natural products 0.000 description 1
- 150000002773 monoterpene derivatives Chemical class 0.000 description 1
- 235000002577 monoterpenes Nutrition 0.000 description 1
- 239000012170 montan wax Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- MFZCIDXOLLEMOO-GYSGTQPESA-N myo-inositol hexanicotinate Chemical compound O([C@H]1[C@@H]([C@H]([C@@H](OC(=O)C=2C=NC=CC=2)[C@@H](OC(=O)C=2C=NC=CC=2)[C@@H]1OC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)OC(=O)C=1C=NC=CC=1)C(=O)C1=CC=CN=C1 MFZCIDXOLLEMOO-GYSGTQPESA-N 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229950006238 nadide Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229920006173 natural rubber latex Polymers 0.000 description 1
- ZYTMANIQRDEHIO-UHFFFAOYSA-N neo-Isopulegol Natural products CC1CCC(C(C)=C)C(O)C1 ZYTMANIQRDEHIO-UHFFFAOYSA-N 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- VWBWQOUWDOULQN-UHFFFAOYSA-N nmp n-methylpyrrolidone Chemical compound CN1CCCC1=O.CN1CCCC1=O VWBWQOUWDOULQN-UHFFFAOYSA-N 0.000 description 1
- 150000007823 ocimene derivatives Chemical class 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
- 229940065472 octyl acrylate Drugs 0.000 description 1
- 229940073665 octyldodecyl myristate Drugs 0.000 description 1
- 235000014593 oils and fats Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 1
- 229960001173 oxybenzone Drugs 0.000 description 1
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 235000005693 perillyl alcohol Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 150000007875 phellandrene derivatives Chemical class 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 229940068065 phytosterols Drugs 0.000 description 1
- 239000001161 piper cubeba l. fruit oil Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001084 poly(chloroprene) Polymers 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920001921 poly-methyl-phenyl-siloxane Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001748 polybutylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005672 polyolefin resin Polymers 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010483 polyoxyethylene sorbitan monopalmitate Nutrition 0.000 description 1
- 239000000249 polyoxyethylene sorbitan monopalmitate Substances 0.000 description 1
- 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
- 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
- 235000010988 polyoxyethylene sorbitan tristearate Nutrition 0.000 description 1
- 239000001816 polyoxyethylene sorbitan tristearate Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 150000007519 polyprotic acids Polymers 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940101027 polysorbate 40 Drugs 0.000 description 1
- 229940113124 polysorbate 60 Drugs 0.000 description 1
- 229940099511 polysorbate 65 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 229940114930 potassium stearate Drugs 0.000 description 1
- IFIDXBCRSWOUSB-UHFFFAOYSA-M potassium;1,5-dichloro-4,6-dioxo-1,3,5-triazin-2-olate Chemical compound [K+].ClN1C(=O)[N-]C(=O)N(Cl)C1=O IFIDXBCRSWOUSB-UHFFFAOYSA-M 0.000 description 1
- ANBFRLKBEIFNQU-UHFFFAOYSA-M potassium;octadecanoate Chemical compound [K+].CCCCCCCCCCCCCCCCCC([O-])=O ANBFRLKBEIFNQU-UHFFFAOYSA-M 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 1
- 239000000770 propane-1,2-diol alginate Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000010666 rose oil Substances 0.000 description 1
- 235000019719 rose oil Nutrition 0.000 description 1
- 239000010668 rosemary oil Substances 0.000 description 1
- 229940058206 rosemary oil Drugs 0.000 description 1
- 229930006696 sabinene Natural products 0.000 description 1
- 239000004248 saffron Substances 0.000 description 1
- 235000013974 saffron Nutrition 0.000 description 1
- 235000017509 safranal Nutrition 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 229940048730 senega Drugs 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- 150000004354 sesquiterpene derivatives Chemical class 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000013464 silicone adhesive Substances 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 229940045920 sodium pyrrolidone carboxylate Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 229940080350 sodium stearate Drugs 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 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
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 239000012177 spermaceti Substances 0.000 description 1
- 229940084106 spermaceti Drugs 0.000 description 1
- 239000010675 spruce oil Substances 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
- 239000010676 star anise oil Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000003784 tall oil Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 210000004341 tarsal joint Anatomy 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 1
- 229930006978 terpinene Natural products 0.000 description 1
- 150000003507 terpinene derivatives Chemical class 0.000 description 1
- 229940116411 terpineol Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- 229930007110 thujone Natural products 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- XJPBRODHZKDRCB-UHFFFAOYSA-N trans-alpha-ocimene Natural products CC(=C)CCC=C(C)C=C XJPBRODHZKDRCB-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- RRBYUSWBLVXTQN-UHFFFAOYSA-N tricyclene Chemical compound C12CC3CC2C1(C)C3(C)C RRBYUSWBLVXTQN-UHFFFAOYSA-N 0.000 description 1
- RRBYUSWBLVXTQN-VZCHMASFSA-N tricyclene Natural products C([C@@H]12)C3C[C@H]1C2(C)C3(C)C RRBYUSWBLVXTQN-VZCHMASFSA-N 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 229940078465 vanillyl butyl ether Drugs 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 235000019509 white turmeric Nutrition 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 239000001841 zingiber officinale Substances 0.000 description 1
- 235000007680 β-tocopherol Nutrition 0.000 description 1
- 239000011590 β-tocopherol Substances 0.000 description 1
- 235000019151 β-tocotrienol Nutrition 0.000 description 1
- 239000011723 β-tocotrienol Substances 0.000 description 1
- FGYKUFVNYVMTAM-WAZJVIJMSA-N β-tocotrienol Chemical compound OC1=CC(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1C FGYKUFVNYVMTAM-WAZJVIJMSA-N 0.000 description 1
- 239000002478 γ-tocopherol Substances 0.000 description 1
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 1
- 235000019150 γ-tocotrienol Nutrition 0.000 description 1
- 239000011722 γ-tocotrienol Substances 0.000 description 1
- OTXNTMVVOOBZCV-WAZJVIJMSA-N γ-tocotrienol Chemical compound OC1=C(C)C(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 OTXNTMVVOOBZCV-WAZJVIJMSA-N 0.000 description 1
- 239000002446 δ-tocopherol Substances 0.000 description 1
- 235000019144 δ-tocotrienol Nutrition 0.000 description 1
- 239000011729 δ-tocotrienol Substances 0.000 description 1
- ODADKLYLWWCHNB-LDYBVBFYSA-N δ-tocotrienol Chemical compound OC1=CC(C)=C2O[C@@](CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)(C)CCC2=C1 ODADKLYLWWCHNB-LDYBVBFYSA-N 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、ロキソプロフェン又はその塩、およびサリチル酸類を含有する医薬組成物に関する。より詳しくは、本発明は、サリチル酸類を含有させることによってロキソプロフェン又はその塩を単独で含む場合よりも抗炎症作用を向上させた、医薬組成物に関する。 The present invention relates to a pharmaceutical composition containing loxoprofen or a salt thereof, and a salicylic acid. More specifically, the present invention relates to a pharmaceutical composition that contains a salicylic acid and thereby has an improved anti-inflammatory effect compared to a pharmaceutical composition containing loxoprofen or a salt thereof alone.
プロピオン酸系非ステロイド性解熱鎮痛消炎剤(NSAIDs)であるロキソプロフェンは、他のNSAIDsと同様にプロスタグランジン生合成の抑制作用に基づく解熱・鎮痛・消炎作用を有する。なお、ロキソプロフェンは経口投与後に胃粘膜刺激作用の弱い未変化体のまま消化管から吸収され、体内で活性体となるプロドラッグであるため、活性体よりも胃粘膜障害は少ないという特徴を有することでも知られている(例えば、非特許文献1参照)。近年、ロキソプロフェンは外用消炎鎮痛剤としてもパップ剤、テープ剤、ゲル剤及び液剤が市販され、臨床に提供されている(例えば、非特許文献2参照)。また、ロキソプロフェンは、皮膚においてもケトン還元酵素によってトランス-OH体(活性体)に変換されることが知られている(例えば、特許文献1参照)。 Loxoprofen, a propionic acid-based nonsteroidal antipyretic, analgesic, and anti-inflammatory drug (NSAID), has antipyretic, analgesic, and anti-inflammatory effects based on the inhibition of prostaglandin biosynthesis, similar to other NSAIDs. Loxoprofen is a prodrug that is absorbed from the digestive tract as an unchanged form with weak gastric mucosa irritation after oral administration and becomes an active form in the body, and is known to have the characteristic of causing less gastric mucosa damage than the active form (see, for example, Non-Patent Document 1). In recent years, loxoprofen has been commercially available as a topical anti-inflammatory and analgesic agent in the form of a poultice, tape, gel, and liquid, and is provided clinically (see, for example, Non-Patent Document 2). It is also known that loxoprofen is converted to the trans-OH form (active form) by ketone reductase in the skin (see, for example, Patent Document 1).
「サリチル酸類」とは、サリチル酸及びその誘導体(例えば、サリチル酸のエステル(具体的には例えば、サリチル酸メチル、サリチル酸エチル、サリチル酸グリコールなど))並びにそれらの塩(例えば、カリウム塩、ナトリウム塩等のアルカリ金属塩;アンモニウム塩など)から選ばれる1種以上を意味する。サリチル酸類は、角質溶解成分、抗菌・殺菌成分や消炎鎮痛成分として知られている(例えば、特許文献2、非特許文献3参照)。 "Salicylic acids" refers to one or more selected from salicylic acid and its derivatives (e.g., esters of salicylic acid (specifically, for example, methyl salicylate, ethyl salicylate, glycol salicylate, etc.)) and their salts (e.g., alkali metal salts such as potassium salts and sodium salts; ammonium salts, etc.). Salicylic acids are known as keratolytic, antibacterial and germicidal, and anti-inflammatory and analgesic ingredients (see, for example, Patent Document 2 and Non-Patent Document 3).
しかしながら、ロキソプロフェンとサリチル酸類とを組み合わせた製剤については十分に知られていない。 However, little is known about preparations that combine loxoprofen with salicylates.
すなわち、本発明は、ロキソプロフェン単独の投与の場合よりも抗炎症効果を向上した医薬組成物を提供することを目的とする。 That is, the present invention aims to provide a pharmaceutical composition that has an improved anti-inflammatory effect compared to administration of loxoprofen alone.
そこで、本発明者らは、上記問題点を解決する為に鋭意検討を重ねた結果、ロキソプロフェンナトリウム水和物とサリチル酸類とを併用することにより、ロキソプロフェン単独の投与の場合より抗炎症効果をさらに向上できることを見出し、本発明を完成するに至った。 As a result of extensive research conducted by the inventors to solve the above problems, they discovered that the anti-inflammatory effect can be improved by combining loxoprofen sodium hydrate with a salicylic acid, as compared to the administration of loxoprofen alone, and thus completed the present invention.
すなわち、本発明によれば以下の発明が提供される。
<1> ロキソプロフェン又はその塩、およびサリチル酸類を含有する医薬組成物。
<2> 抗炎症組成物である、<1> に記載の医薬組成物。
<3> 医薬組成物における前記サリチル酸類の含有量が、0.001~50質量%である、<1>または<2>に記載の医薬組成物。
<4> 医薬組成物における前記ロキソプロフェン又はその塩の含有量が、0.1~15質量%である、<1>または<2>に記載の医薬組成物。
<5> ロキソプロフェン又はその塩の含有量に対するサリチル酸類の含有量の質量比(サリチル酸類/ロキソプロフェン又はその塩)が1.0×10-5~1000である、<1>または<2>に記載の医薬組成物。
<6> 剤形が外用液剤、軟膏剤、クリーム剤、スプレー剤、ゲル剤、貼付剤、又は外用固形剤である、<1>または<2>に記載の医薬組成物。
<7> サリチル酸類を含有する、ロキソプロフェン又はその塩の抗炎症作用の増強剤。
<8> サリチル酸類を含有する、ロキソプロフェン又はその塩の抗炎症作用の持続剤。
That is, according to the present invention, the following inventions are provided.
<1> A pharmaceutical composition comprising loxoprofen or a salt thereof and a salicylic acid.
<2> The pharmaceutical composition according to <1>, which is an anti-inflammatory composition.
<3> The pharmaceutical composition according to <1> or <2>, wherein the content of the salicylic acid in the pharmaceutical composition is 0.001 to 50 mass%.
<4> The pharmaceutical composition according to <1> or <2>, wherein the content of the loxoprofen or a salt thereof in the pharmaceutical composition is 0.1 to 15 mass%.
<5> The pharmaceutical composition according to <1> or <2>, wherein the mass ratio of the content of the salicylic acids to the content of the loxoprofen or a salt thereof (salicylic acids/loxoprofen or a salt thereof) is 1.0×10 −5 to 1,000.
<6> The pharmaceutical composition according to <1> or <2>, wherein the dosage form is a liquid for external use, an ointment, a cream, a spray, a gel, a patch, or a solid for external use.
<7> An agent for enhancing the anti-inflammatory effect of loxoprofen or a salt thereof, which contains a salicylic acid.
<8> An agent for sustaining the anti-inflammatory effect of loxoprofen or a salt thereof, which contains a salicylic acid.
本発明の医薬組成物は、優れた抗炎症効果を発揮することができる。ロキソプロフェンナトリウム水和物とサリチル酸類の一つであるサリチル酸グリコールを併用することにより、ロキソプロフェン単独の投与の場合より抗炎症効果をさらに向上できることは予想外な効果である。 The pharmaceutical composition of the present invention can exert an excellent anti-inflammatory effect. It is an unexpected effect that the combined use of loxoprofen sodium hydrate and glycol salicylate, which is a salicylic acid, can further improve the anti-inflammatory effect compared to the administration of loxoprofen alone.
本発明の医薬組成物は、ロキソプロフェン又はその塩、およびサリチル酸類を含有する。本発明の医薬組成物は、抗炎症組成物として有用である。 The pharmaceutical composition of the present invention contains loxoprofen or a salt thereof, and a salicylic acid. The pharmaceutical composition of the present invention is useful as an anti-inflammatory composition.
プロピオン酸系非ステロイド性解熱鎮痛消炎剤(NSAIDs)であるロキソプロフェンは、他のNSAIDsと同様にプロスタグランジン生合成の抑制作用に基づく解熱・鎮痛・消炎作用を有する。ロキソプロフェンは経口投与後に胃粘膜刺激作用の弱い未変化体のまま消化管から吸収され、体内で活性体となるプロドラッグであるため、活性体よりも胃粘膜障害は少ないという特徴を有することでも知られている。また、ロキソプロフェンは、皮膚においてもケトン還元酵素によってトランス-OH体(活性体)に変換されることが知られており、近年、ロキソプロフェンは外用消炎鎮痛剤としてもパップ剤、テープ剤、ゲル剤及び液剤が市販され、臨床に提供されている。 Loxoprofen, a propionic acid-based nonsteroidal antipyretic, analgesic, and anti-inflammatory drug (NSAID), has antipyretic, analgesic, and anti-inflammatory effects based on the inhibition of prostaglandin biosynthesis, similar to other NSAIDs. Loxoprofen is a prodrug that is absorbed from the digestive tract as an unchanged form with weak gastric mucosa irritation after oral administration and becomes an active form in the body, so it is known to cause less gastric mucosa damage than the active form. Loxoprofen is also known to be converted to the trans-OH form (active form) by ketone reductase in the skin, and in recent years, loxoprofen has been commercially available as a topical anti-inflammatory and analgesic agent in the form of poultices, tapes, gels, and liquids, and is provided clinically.
本発明において、「ロキソプロフェン又はその塩」とは、ロキソプロフェン又はその塩、並びにそれらの水和物を含むものである。ロキソプロフェンの塩としては、薬理学的に許容できる塩が好ましく、より好ましくは、ロキソプロフェンナトリウム又はロキソプロフェンナトリウム水和物(ロキソプロフェンナトリウム・2水和物と示すこともある)であり、さらに好ましくは、ロキソプロフェンナトリウム水和物である。なお、本明細書においてロキソプロフェンと言う場合には、ロキソプロフェン又はその塩、並びにそれらの水和物を包含するものとする。 In the present invention, "loxoprofen or a salt thereof" includes loxoprofen or a salt thereof, as well as hydrates thereof. As a salt of loxoprofen, a pharmacologically acceptable salt is preferred, more preferably loxoprofen sodium or loxoprofen sodium hydrate (sometimes referred to as loxoprofen sodium dihydrate), and even more preferably loxoprofen sodium hydrate. In this specification, the term loxoprofen includes loxoprofen or a salt thereof, as well as hydrates thereof.
本発明におけるロキソプロフェンは、ロキソプロフェンナトリウム水和物として第18改正日本薬局方に収載されている。 The loxoprofen used in the present invention is listed in the 18th revised edition of the Japanese Pharmacopoeia as loxoprofen sodium hydrate.
本発明におけるサリチル酸類とは、サリチル酸及びその誘導体(例えば、サリチル酸のエステル(具体的には例えば、サリチル酸メチル、サリチル酸エチル、サリチル酸グリコールなど))並びにそれらの塩(例えば、カリウム塩、ナトリウム塩等のアルカリ金属塩;アンモニウム塩など)から選ばれる1種以上を意味する。
本発明においてサリチル酸類としては、抗炎症効果作用の増強の観点から、サリチル酸、サリチル酸グリコール、サリチル酸ナトリウム及びサリチル酸メチルよりなる群から選ばれる1種以上が好ましく、サリチル酸グリコール及びサリチル酸メチルよりなる群から選ばれる1種以上がより好ましく、サリチル酸グリコールが特に好ましい。
なお、これらはいずれも公知の化合物であり、公知の方法により製造できるほか、市販のものを用いることができる。
The salicylic acids in the present invention refer to one or more selected from salicylic acid and its derivatives (e.g., esters of salicylic acid (specifically, for example, methyl salicylate, ethyl salicylate, glycol salicylate, etc.)) and salts thereof (e.g., alkali metal salts such as potassium salts and sodium salts; ammonium salts, etc.).
In the present invention, as the salicylic acids, from the viewpoint of enhancing the anti-inflammatory effect, one or more types selected from the group consisting of salicylic acid, glycol salicylate, sodium salicylate, and methyl salicylate are preferred, one or more types selected from the group consisting of glycol salicylate and methyl salicylate are more preferred, and glycol salicylate is particularly preferred.
These are all known compounds and can be produced by known methods, or commercially available products can be used.
本発明の医薬組成物は、さらにアルコール類を含有してもよい。
本発明におけるアルコール類とは低級アルコールおよび多価アルコールのことを指す。本発明における低級アルコールとは、可溶化剤、基剤、保存剤、溶剤、溶解補助剤等の用途で外用剤に用いられる炭素数1~4個の脂肪族アルコール類であり、例えば、メタノール、エタノール(エチルアルコールとも言う)、プロパノール、イソプロパノール(イソプロピルアルコールとも言う)、およびブチルアルコール等からなる群より選ばれる1種または2種以上であり、好ましくはエタノールである。エタノール含量が99.5体積%以上のものは無水エタノールとも呼ばれる。
The pharmaceutical composition of the present invention may further contain an alcohol.
The alcohols in the present invention refer to lower alcohols and polyhydric alcohols. The lower alcohols in the present invention refer to aliphatic alcohols having 1 to 4 carbon atoms that are used in external preparations for the purposes of solubilizing agents, bases, preservatives, solvents, dissolving aids, etc., and are, for example, one or more selected from the group consisting of methanol, ethanol (also called ethyl alcohol), propanol, isopropanol (also called isopropyl alcohol), and butyl alcohol, etc., and are preferably ethanol. Ethanol with an ethanol content of 99.5% by volume or more is also called absolute ethanol.
本発明における多価アルコールとは、可溶化剤、基剤、湿潤剤、粘稠剤、溶剤、溶解補助剤等の用途で外用剤に用いられる、分子内に水酸基が2個以上あるアルコールであり、例えば、プロピレングリコール、1,3‐ブチレングリコール、マクロゴール(ポリエチレングリコールともいう)、グリセリン、D‐ソルビトール、ジプロピレングリコールであり、医薬品添加物事典2021に収載されている。なお、マクロゴールの分子量は特に限定されないが、例えば、数平均分子量で200~20000であってもよい。
また、本発明におけるアルコール類の分子量は、特に限定されないが、例えば、400以下であってもよく、400未満であることが好ましく、300以下であることがより好ましく、250以下であることがさらに好ましく、200以下であることが特に好ましく、100以下であってもよい。
The polyhydric alcohol in the present invention is an alcohol having two or more hydroxyl groups in the molecule, which is used in external preparations for purposes such as solubilizers, bases, humectants, thickeners, solvents, and dissolution aids, and examples of such alcohols include propylene glycol, 1,3-butylene glycol, macrogol (also called polyethylene glycol), glycerin, D-sorbitol, and dipropylene glycol, which are listed in the Pharmaceutical Additives Encyclopedia 2021. The molecular weight of macrogol is not particularly limited, and may be, for example, 200 to 20,000 in number average molecular weight.
In addition, the molecular weight of the alcohols in the present invention is not particularly limited, but may be, for example, 400 or less, preferably less than 400, more preferably 300 or less, even more preferably 250 or less, particularly preferably 200 or less, and may be 100 or less.
また、本発明の医薬組成物における、サリチル酸類の含有量は、特に限定されないが、好ましくは、医薬組成物全量に対して、0.001~50質量%であり、より好ましくは、0.01~20質量%であり、さらに好ましくは0.1~20質量%であり、特に好ましくは0.1~10質量%である。なお、医薬組成物の剤形が貼付剤(パップ剤、テープ剤)の場合においても、サリチル酸類の含有量は、特に限定されないが、好ましくは、貼付剤の膏体全量に対して、0.001~50質量%であり、より好ましくは、0.01~20質量%であり、特に好ましくは0.1~10質量%である。 The content of salicylic acids in the pharmaceutical composition of the present invention is not particularly limited, but is preferably 0.001 to 50% by mass, more preferably 0.01 to 20% by mass, even more preferably 0.1 to 20% by mass, and particularly preferably 0.1 to 10% by mass, based on the total amount of the pharmaceutical composition. When the pharmaceutical composition is in the form of a patch (poultice or tape), the content of salicylic acids is not particularly limited, but is preferably 0.001 to 50% by mass, more preferably 0.01 to 20% by mass, and particularly preferably 0.1 to 10% by mass, based on the total amount of the paste in the patch.
本発明の医薬組成物が、アルコールを含有する場合、アルコールの質量に対する、サリチル酸類の含有量の比(サリチル酸類/アルコール質量比)は、特に限定されないが、好ましくは1.0×10-3~100であり、より好ましくは、1.4×10-3~10であり、さらに好ましくは2.0×10-3~5.0である。
本発明の医薬組成物が、低級アルコールを含有する場合、低級アルコールの質量に対する、サリチル酸類の含有量の比(サリチル酸類/低級アルコール質量比)は、特に限定されないが、好ましくは1.0×10-3~100であり、より好ましくは、1.4×10-3~10であり、さらに好ましくは2.0×10-3~5.0である。
本発明の医薬組成物が、多価アルコールを含有する場合、多価アルコールの質量に対する、サリチル酸類の含有量の比(サリチル酸類/多価アルコール質量比)は、特に限定されないが、好ましくは1.0×10-3~100であり、より好ましくは、1.4×10-3~10であり、さらに好ましくは2.0×10-3~5.0である。
When the pharmaceutical composition of the present invention contains alcohol, the ratio of the content of salicylic acids to the mass of alcohol (salicylic acids/alcohol mass ratio) is not particularly limited, but is preferably 1.0×10 -3 to 100, more preferably 1.4×10 -3 to 10, and even more preferably 2.0×10 -3 to 5.0.
When the pharmaceutical composition of the present invention contains a lower alcohol, the ratio of the content of salicylic acids to the mass of the lower alcohol (salicylic acids/lower alcohol mass ratio) is not particularly limited, but is preferably 1.0×10 -3 to 100, more preferably 1.4×10 -3 to 10, and even more preferably 2.0×10 -3 to 5.0.
When the pharmaceutical composition of the present invention contains a polyhydric alcohol, the ratio of the content of salicylic acids to the mass of the polyhydric alcohol (salicylic acids/polyhydric alcohol mass ratio) is not particularly limited, but is preferably 1.0×10 -3 to 100, more preferably 1.4×10 -3 to 10, and even more preferably 2.0×10 -3 to 5.0.
また、本発明の医薬組成物における、ロキソプロフェン又はその塩(例えば、ロキソプロフェンナトリウム水和物)の含有量は、特に限定されないが、好ましくは、医薬組成物全量に対して、0.1~15質量%であり、より好ましくは、0.5~10質量%である。なお、医薬組成物の剤形が貼付剤(パップ剤、テープ剤)の場合においても、ロキソプロフェン又はその塩(例えば、ロキソプロフェンナトリウム水和物)の含有量は、特に限定されないが、好ましくは、貼付剤の膏体全量に対して、0.1~15質量%であり、より好ましくは、0.5~10質量%である。 The content of loxoprofen or a salt thereof (e.g., loxoprofen sodium hydrate) in the pharmaceutical composition of the present invention is not particularly limited, but is preferably 0.1 to 15% by mass, more preferably 0.5 to 10% by mass, based on the total amount of the pharmaceutical composition. Even when the pharmaceutical composition is in the form of a patch (poultice or tape), the content of loxoprofen or a salt thereof (e.g., loxoprofen sodium hydrate) is not particularly limited, but is preferably 0.1 to 15% by mass, more preferably 0.5 to 10% by mass, based on the total amount of the paste in the patch.
本発明の医薬組成物が、アルコールを含有する場合、アルコールの質量に対する、ロキソプロフェン又はその塩の含有量の比(ロキソプロフェン又はその塩/アルコール質量比)は、特に限定されないが、好ましくは1.0×10-3~150であり、より好ましくは、1.4×10-3~100であり、さらに好ましくは、2.0×10-3~35である。
本発明の医薬組成物が、低級アルコールを含有する場合、低級アルコールの質量に対する、ロキソプロフェン又はその塩の含有量の比(ロキソプロフェン又はその塩/低級アルコール質量比)は、特に限定されないが、好ましくは1.0×10-3~150であり、より好ましくは、1.4×10-3~100であり、さらに好ましくは、2.0×10-3~20である。
本発明の医薬組成物が、多価アルコールを含有する場合、多価アルコールの質量に対する、ロキソプロフェン又はその塩の含有量の比(ロキソプロフェン又はその塩/多価アルコール質量比)は、特に限定されないが、好ましくは1.0×10-3~150であり、より好ましくは、1.4×10-3~100であり、さらに好ましくは、2.0×10-3~35である。
When the pharmaceutical composition of the present invention contains alcohol, the ratio of the content of loxoprofen or a salt thereof to the mass of alcohol (loxoprofen or a salt thereof/alcohol mass ratio) is not particularly limited, but is preferably 1.0×10 -3 to 150, more preferably 1.4×10 -3 to 100, and even more preferably 2.0×10 -3 to 35.
When the pharmaceutical composition of the present invention contains a lower alcohol, the ratio of the content of loxoprofen or a salt thereof to the mass of the lower alcohol (loxoprofen or a salt thereof/lower alcohol mass ratio) is not particularly limited, but is preferably 1.0×10 -3 to 150, more preferably 1.4×10 -3 to 100, and even more preferably 2.0×10 -3 to 20.
When the pharmaceutical composition of the present invention contains a polyhydric alcohol, the ratio of the content of loxoprofen or a salt thereof to the mass of the polyhydric alcohol (loxoprofen or a salt thereof/polyhydric alcohol mass ratio) is not particularly limited, but is preferably 1.0×10 -3 to 150, more preferably 1.4×10 -3 to 100, and even more preferably 2.0×10 -3 to 35.
本発明の医薬組成物におけるサリチル酸類とロキソプロフェン又はその塩との質量比は、特に限定されないが、サリチル酸類/ロキソプロフェン又はその塩(サリチル酸類/Lox質量比)が1.0×10-5~1000であってよく、5.0×10-5~750であることが好ましく、6.6×10-5~500であることがより好ましく、0.1~20であることが特に好ましい。 The mass ratio of salicylates to loxoprofen or a salt thereof in the pharmaceutical composition of the present invention is not particularly limited, but the salicylic acids/loxoprofen or a salt thereof (salicylic acids/Lox mass ratio) may be 1.0× 10-5 to 1,000, preferably 5.0× 10-5 to 750, more preferably 6.6× 10-5 to 500, and particularly preferably 0.1 to 20.
また、本発明の医薬組成物におけるアルコールの含有量の範囲は、特に限定されないが、 剤形に応じて選択してよく、 好ましくは、医薬組成物全量に対して、0.1~70.0質量%であってもよい。なお、医薬組成物の剤形が貼付剤(パップ剤、テープ剤)の場合においても、アルコールの含有量は、特に限定されないが、好ましくは、貼付剤の膏体全量に対して、0.1~70.0質量%である。
また、本発明の医薬組成物における低級アルコールの含有量の範囲は、特に限定されないが、剤形に応じて選択してよく、好ましくは、医薬組成物全量に対して、0.1~70.0質量%であり、より好ましくは、0.1~50.0質量%である。
The range of the alcohol content in the pharmaceutical composition of the present invention is not particularly limited, but may be selected depending on the dosage form, and may be preferably 0.1 to 70.0% by mass based on the total amount of the pharmaceutical composition. Even when the dosage form of the pharmaceutical composition is a patch (poultice, tape), the alcohol content is not particularly limited, but is preferably 0.1 to 70.0% by mass based on the total amount of the paste of the patch.
Furthermore, the range of the content of the lower alcohol in the pharmaceutical composition of the present invention is not particularly limited, and may be selected depending on the dosage form, and is preferably 0.1 to 70.0% by mass, more preferably 0.1 to 50.0% by mass, based on the total amount of the pharmaceutical composition.
例えば、本発明の医薬組成物が外用液剤・ゲル剤の場合には、低級アルコールの添加量含有量の範囲は、例えば、外用液剤・ゲル剤の全量に対して、特に限定されないが、好ましくは10.0~70.0質量%であり、より好ましくは、10.0~60.0質量%である。
例えば、本発明の医薬組成物がパップ剤の場合には、低級アルコールの添加量含有量の範囲は、例えば、パップ剤の膏体全量に対して、好ましくは0.1~50質量%であり、より好ましくは0.1%~30質量%である。
例えば、本発明の医薬組成物がテープ剤の場合には、低級アルコールを含有する場合と含有しない場合とがあり、低級アルコールを含有する場合の含有量の範囲は、例えば、テープ剤の膏体全量に対して、好ましくは0.1~10質量%であり、より好ましくは0.1%~5質量%である。
For example, when the pharmaceutical composition of the present invention is a liquid or gel for external use, the range of the content of the lower alcohol added is not particularly limited, but is preferably 10.0 to 70.0 mass%, and more preferably 10.0 to 60.0 mass%, based on the total amount of the liquid or gel for external use.
For example, when the pharmaceutical composition of the present invention is a cataplasm, the range of the content of the lower alcohol added is, for example, preferably 0.1 to 50% by mass, and more preferably 0.1% to 30% by mass, based on the total amount of the cataplasm.
For example, when the pharmaceutical composition of the present invention is in the form of a tape preparation, it may or may not contain a lower alcohol. When a lower alcohol is contained, the content range is, for example, preferably 0.1 to 10% by mass, and more preferably 0.1% to 5% by mass, relative to the total amount of the paste in the tape preparation.
さらに、本発明の医薬組成物における多価アルコールの含有量の範囲は、特に限定されないが、剤形に応じて選択してよく、好ましくは医薬組成物全量に対して、0.1~70質量%であり、より好ましくは0.1~20質量%であり、より好ましくは0.5~20質量%であり、さらに好ましくは、1.0~15質量%である。
例えば、本発明の医薬組成物が外用液剤・ゲル剤の場合には、多価アルコールの添加量含有量の範囲は、特に限定されないが、例えば、外用液剤・ゲル剤の全量に対して、好ましくは0.5~20質量%であり、より好ましくは、1.0~15質量%である。
Furthermore, the range of the content of the polyhydric alcohol in the pharmaceutical composition of the present invention is not particularly limited, and may be selected depending on the dosage form, and is preferably 0.1 to 70 mass %, more preferably 0.1 to 20 mass %, more preferably 0.5 to 20 mass %, and even more preferably 1.0 to 15 mass %, based on the total amount of the pharmaceutical composition.
For example, when the pharmaceutical composition of the present invention is a liquid or gel for external use, the range of the content of the added amount of the polyhydric alcohol is not particularly limited, but is, for example, preferably 0.5 to 20 mass %, more preferably 1.0 to 15 mass %, based on the total amount of the liquid or gel for external use.
例えば、本発明の医薬組成物がパップ剤の場合には、多価アルコールの添加量含有量の範囲は、特に限定されないが、例えば、パップ剤の膏体全量に対して、好ましくは0.1~70質量%であり、より好ましくは3~60質量%である。
例えば、本発明の医薬組成物がテープ剤の場合には、多価アルコールを含有する場合と含有しない場合とがあり、多価アルコールを含有する場合の含有量の範囲は、例えば、テープ剤の膏体全量に対して、好ましくは0.1~15質量%であり、より好ましくは0.1%~10質量%である。
For example, when the pharmaceutical composition of the present invention is a cataplasm, the range of the content of the polyhydric alcohol added is not particularly limited, but is, for example, preferably 0.1 to 70% by mass, and more preferably 3 to 60% by mass, based on the total amount of the cataplasm.
For example, when the pharmaceutical composition of the present invention is in the form of a tape preparation, it may or may not contain a polyhydric alcohol. When a polyhydric alcohol is contained, the content range is, for example, preferably 0.1 to 15% by mass, and more preferably 0.1% to 10% by mass, relative to the total amount of the paste in the tape preparation.
また、医薬組成物のpHの範囲は、特に限定されないが、好ましくは5.0~7.5であり、より好ましくは6.0~7.5である。 The pH range of the pharmaceutical composition is not particularly limited, but is preferably 5.0 to 7.5, and more preferably 6.0 to 7.5.
本発明の医薬組成物において、上記成分以外の医薬組成物に通常使用される、薬物や医薬品添加物を添加することができる。 The pharmaceutical composition of the present invention may contain drugs and pharmaceutical additives that are typically used in pharmaceutical compositions other than the above ingredients.
本発明の医薬組成物においては、さらに成分(A)を含んでいてもよく、前記成分(A)が下記成分(A―1)~(A―11)よりなる群から選ばれる1種以上を含有してよい。
(A-1)トコフェロール類 ;
(A-2)テルペン類;
(A-3)グリチルリチン酸類 ;
(A-4)生薬類;
(A-5)トラネキサム酸類;
(A-6)バニロイド類;
(A-7)ニコチン酸類;
(A-8)クロルフェニラミン類 ;
(A-9)ジフェンヒドラミン類 ;
(A-10)ピロリドン類;
(A-11)無機塩 ;
The pharmaceutical composition of the present invention may further contain component (A), and the component (A) may contain one or more types selected from the group consisting of the following components (A-1) to (A-11).
(A-1) Tocopherols;
(A-2) terpenes;
(A-3) Glycyrrhizic acids;
(A-4) Herbal medicines;
(A-5) Tranexamic acids;
(A-6) Vanilloids;
(A-7) nicotinic acids;
(A-8) Chlorpheniramines;
(A-9) Diphenhydramines;
(A-10) Pyrrolidones;
(A-11) inorganic salt;
(A-1)トコフェロール類としては、トコフェロール、トコトリエノール及びそれらの誘導体(例えば、酢酸エステル、コハク酸エステル、ニコチン酸エステル等のエステル化誘導体など)並びにそれらの塩(例えば、カルシウム塩、マグネシウム塩等のアルカリ土類金属塩など)を挙げることができる。トコフェロールとしては、α-トコフェロール、β-トコフェロール、γ-トコフェロール、δ-トコフェロールのいずれであってもよいが、α-トコフェロールが好ましい。また、トコトリエノールとしては、α-トコトリエノール、β-トコトリエノール、γ-トコトリエノール、δ-トコトリエノールのいずれであってもよいが、α-トコトリエノールが好ましい。トコフェロール類としては、トコフェロール酢酸エステルが特に好ましい。 (A-1) Examples of tocopherols include tocopherol, tocotrienol, and derivatives thereof (e.g., esterified derivatives such as acetate, succinate, and nicotinate) and salts thereof (e.g., alkaline earth metal salts such as calcium salt and magnesium salt). The tocopherol may be any of α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol, with α-tocopherol being preferred. The tocotrienol may be any of α-tocotrienol, β-tocotrienol, γ-tocotrienol, and δ-tocotrienol, with α-tocotrienol being preferred. The tocopherol is particularly preferably tocopherol acetate.
トコフェロール類を使用する場合における医薬組成物におけるトコフェロール類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.03~4質量%がより好ましく、0.05~2質量%が特に好ましい。 When tocopherols are used, the content of tocopherols in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.03 to 4% by mass, and particularly preferably 0.05 to 2% by mass, based on the total mass of the pharmaceutical composition.
(A-2)テルペン類とは、テルペン炭化水素のほか、テルペンアルコール、テルペンアルデヒド、テルペンケトン、テルペンオキシド、テルペンラクトンなどを包含する総称(テルペノイド)を意味し、その構造は特に限定されるものではなく、モノテルペン、セスキテルペン又はそれらの誘導体等が挙げられる。また、環式でも鎖式でもよい。テルペン類としては、例えば、イソボルネオール、イロン、オシメン、カルベオール、カルボタナセトン、カルボメントン、カルボン、カレン、カロン、カンフェン、カンフル、ゲラニオール、サビネン、サフラナール、シクロシトラール、シトラール、シトロネラール、シトロネル酸、シトロネロール、シネオール、シメン、シルベストレン、チモール、イソツジョール、ツジョン、テルピネオール、テルピネン、テルピノレン、トリシクレン、ネロール、ピネン、ピノカンフェオール、ピノール、ピペリテノン、フェランドラール、フェランドレン、フェンチェン、フェンチルアルコール、ペリリルアルコール、ペリルアルデヒド、ボルネオール、ミルセン、メントール、メントン、ヨノール、ヨノン、リナロール、リモネン等が挙げられる。 (A-2) Terpenes are a general term (terpenoids) that includes terpene hydrocarbons, terpene alcohols, terpene aldehydes, terpene ketones, terpene oxides, terpene lactones, etc., and their structure is not particularly limited, and examples include monoterpenes, sesquiterpenes, and derivatives thereof. They may be cyclic or chain. Examples of terpenes include isoborneol, irone, ocimene, carveol, carbotanacetone, carbomenthone, carvone, carene, calone, camphene, camphor, geraniol, sabinene, safranal, cyclocitral, citral, citronellal, citronellic acid, citronellol, cineole, cymene, sylvestrene, thymol, isothujol, thujone, terpineol, terpinene, terpinolene, tricyclene, nerol, pinene, pinocampheol, pinol, piperitenone, phellandral, phellandrene, fenchene, fenchyl alcohol, perillyl alcohol, perillaldehyde, borneol, myrcene, menthol, menthone, ionol, ionone, linalool, and limonene.
テルペン類としては、テルペン類を含む精油を用いてもよい。精油としては、例えば、アニス油、イランイラン油、イリス油、ウイキョウ油、オレンジ油、カナンガ油、カミツレ油、カヤプト油、カラウェー油、クベブ油、グレープフルーツ油、ケイヒ油、コリアンダー油、サフラン油、サンショウ油、シソ油、シトリオドラ油、シトロネラ油、ショウキョウ油、ショウズク油、樟脳油、ジンジャーグラス油、スペアミント油、セイヨウハッカ油、ゼラニウム油、ダイウイキョウ油、チョウジ油、テレビン油、トウヒ油、ネロリ油、バジル油、ハッカ油、パルマローザ油、ピメント油、プチグレン油、ベイ油、ペニローヤル油、ヘノポジ油、ベルガモット油、ボアドローズ油、ホウショウ油、マジョラン油、マンダリン油、メリッサ油、ユーカリ油、ライム油、ラベンダー油、リナロエ油、レモン油、レモングラス油、ローズ油、ローズマリー油、ローマカミツレ油等が挙げられ、これらを単独で又は2種以上組み合わせて用いてもよい。 Terpenes may be used as essential oils containing terpenes. Examples of essential oils include anise oil, ylang-ylang oil, iris oil, fennel oil, orange oil, cananga oil, chamomile oil, kayaputo oil, caraway oil, cubeb oil, grapefruit oil, cinnamon oil, coriander oil, saffron oil, pepper oil, perilla oil, citriodora oil, citronella oil, ginger oil, cardamom oil, camphor oil, ginger grass oil, spearmint oil, peppermint oil, geranium oil, star anise oil, clove oil, and terephthalic acid oil. Examples of such oils include bottle oil, spruce oil, neroli oil, basil oil, peppermint oil, palmarosa oil, pimento oil, petitgrain oil, bay oil, pennyroyal oil, henopodium oil, bergamot oil, borealis oil, hosho oil, marjolan oil, mandarin oil, melissa oil, eucalyptus oil, lime oil, lavender oil, linaloe oil, lemon oil, lemongrass oil, rose oil, rosemary oil, and Roman chamomile oil. These may be used alone or in combination of two or more.
テルペン類としては、好ましくは、l-メントール、dl―カンフル、メントキシプロパンジオール(3-(メントキシ)-1,2-プロパンジオール)、3-(l-メントキシ)-2-メチルプロパン-1,2-ジオール、p-メンタン-3,8-ジオール、イソプレゴール、チモール、ハッカ油、ユーカリ油などを使用することができる。 Preferably, terpenes that can be used include l-menthol, dl-camphor, menthoxypropanediol (3-(menthoxy)-1,2-propanediol), 3-(l-menthoxy)-2-methylpropane-1,2-diol, p-menthane-3,8-diol, isopulegol, thymol, peppermint oil, and eucalyptus oil.
テルペン類を使用する場合における医薬組成物におけるテルペン類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.05~6質量%がより好ましく、0.1~4質量%が特に好ましい。 When terpenes are used, the content of the terpenes in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.05 to 6% by mass, and particularly preferably 0.1 to 4% by mass, based on the total mass of the pharmaceutical composition.
(A-3)グリチルリチン酸類としては、例えば、グリチルリチン酸またはその塩、グリチルレチン酸またはその塩を挙げることができる。塩としては、例えば、カリウム塩、ナトリウム塩等のアルカリ金属塩;アンモニウム塩などを挙げることができる。また、グリチルリチン酸類としては、グリチルリチン酸類を含有するカンゾウ(甘草)やその抽出物を用いてもよい。 (A-3) Examples of glycyrrhizic acids include glycyrrhizic acid or its salts, and glycyrrhetinic acid or its salts. Examples of salts include alkali metal salts such as potassium salts and sodium salts; and ammonium salts. In addition, licorice (liquorice) or an extract thereof, which contains glycyrrhizic acids, may be used as glycyrrhizic acids.
グリチルリチン酸類を使用する場合における医薬組成物におけるグリチルリチン酸類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.05~4質量%がより好ましく、0.1~3質量%が特に好ましい。 When glycyrrhizic acids are used, the content of glycyrrhizic acids in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.05 to 4% by mass, and particularly preferably 0.1 to 3% by mass, based on the total mass of the pharmaceutical composition.
(A-4)生薬類としては、例えば、カンゾウ、アルニカチンキ、アカメガシワ、アセンヤク、インヨウカク、ウイキョウ、ウコン、エンゴサク、オウゴン、オウセイ、オウバク、オウヒ、オウレン、オンジ、ガジュツ、カノコソウ、カミツレ、カロニン、キキョウ、キョウニン、クコシ、クコヨウ、ケイガイ、ケイヒ、ケツメイシ、ゲンチアナ、ゲンノショウコ、コウカ、コウブシ、ゴオウ、ゴミシ、サイシン、サンシシ、サンショウ、シオン、ジコッピ、シコン、シャクヤク、ジャコウ、シャジン、シャゼンシ、シャゼンソウ、獣胆(ユウタン(熊胆)を含む)、ショウキョウ、ジリュウ、シンイ、セイヨウトチノキ、セキサン、セネガ、センキュウ、ゼンコ、センブリ、ソウジュツ、ソウハクヒ、ソヨウ、タイサン、チクセツニンジン、チンピ、トウキ、トコン、ナンテンジツ、ニンジン、バイモ、バクモンドウ、ハンゲ、バンコウカ、ハンピ、ビャクシ、ビャクジュツ、ブクリョウ、ボタンピ、ヨウバイヒ、ロクジョウ等の生薬及びこれらの抽出物(エキス、チンキ、乾燥エキス等)等が挙げられる。なお、カンゾウは、グリチルリチン酸類として用いてもよく、生薬類としても用いてもよく、グリチルリチン酸類及び生薬類の両方の役割を兼ねて用いてもよい。 (A-4) Examples of herbal medicines include licorice, tincture of arnica, Mallotus japonicus, Acacia japonica, Coix seed, fennel, turmeric, Corydalis chinensis, Scutellaria baicalensis, Chinese holly, Phellodendron bark, Coptis chinensis, Onji, Zedoary, valerian, chamomile, calonin, bellflower, apricot kernel, wolfberry, wolfberry, cinnamon bark, Cassia japonica, gentian, geranium herb, koka ka, magnolia berry, bezoar, gomoku, saishin, shiso, Japanese pepper, ash, japonicus, Lithospermum officinalis, peony root, musk, sappanha, Examples of herbal medicines include Shazenshi, Shazensou, animal gall (including Yutan (bear gall)), Zingiber officinale, Jiryu, Xin-i, European horse chestnut, Sekisan, Senega, Cnidium rhizome, Zenko, Swertia britannica, Atractylodes rhizome, Sohakuhi, Soybean, Taisan, Chikusetsuninjin, Tianpi, Dongqi, Ipecac, Nandinafrica, Carrot, Fritillaria, Bakumondou, Pinellia gracilis, Bankouka, Hanpi, Byakushi, Byakushu, Poria columbine, Peony peel, Japanese laurel, Rokujo, and their extracts (extracts, tinctures, dried extracts, etc.). Licorice may be used as a glycyrrhizic acid compound, as a herbal medicine, or it may be used as both a glycyrrhizic acid compound and a herbal medicine.
生薬類を使用する場合における医薬組成物における生薬類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.05~4質量%がより好ましく、0.1~3質量%が特に好ましい。 When herbal medicines are used, the content of the herbal medicines in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.05 to 4% by mass, and particularly preferably 0.1 to 3% by mass, based on the total mass of the pharmaceutical composition.
(A-5)トラネキサム酸類は、例えば、トラネキサム酸またはその塩、トラネキサム酸誘導体またはその塩を含んでいてもよい。
トラネキサム酸の塩としては、特に制限はないが、具体的には、ナトリウム、カリウム等のアルカリ金属塩;カルシウム、マグネシウム等のアルカリ土類金属塩;アルミニウム、鉄、亜鉛等の金属塩;リジン、アルギニン、ヒスチジン、オルニチン等の塩基性アミノ酸塩;アンモニウム、モノエタノールアミン、ジエタノールアミン、トリエタノールアミン、ステアリルアミン等の有機アミン塩等が挙げられる。また、トラネキサム酸誘導体またはその塩であってもよく、具体的には、トラネキサム酸セチルエステル等のエステル誘導体;トラネキサム酸メチルアミド等のアミド誘導体が例示できる。
(A-5) Tranexamic acids may include, for example, tranexamic acid or a salt thereof, or a tranexamic acid derivative or a salt thereof.
The salt of tranexamic acid is not particularly limited, and specific examples thereof include alkali metal salts such as sodium and potassium, alkaline earth metal salts such as calcium and magnesium, metal salts such as aluminum, iron and zinc, basic amino acid salts such as lysine, arginine, histidine and ornithine, organic amine salts such as ammonium, monoethanolamine, diethanolamine, triethanolamine and stearylamine, etc. Also usable are tranexamic acid derivatives or salts thereof, and specific examples thereof include ester derivatives such as tranexamic acid cetyl ester, and amide derivatives such as tranexamic acid methylamide.
トラネキサム酸類を使用する場合における医薬組成物におけるトラネキサム酸類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.05~4質量%がより好ましく、0.1~2質量%が特に好ましい。 When tranexamic acids are used, the content of tranexamic acids in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.05 to 4% by mass, and particularly preferably 0.1 to 2% by mass, based on the total mass of the pharmaceutical composition.
(A-6)バニロイド類は、バニリル基を含む化合物の総称である、本発明におけるバニロイド類としては、バニリル基を含む化合物であれば特に限定されず、例えば、バニリン、バニリン酸、カプサイシン、バニリルマンデル酸(VMA)、バニリルブチルエーテル(4-ブトキシメチル-2-メトキシフェノール)などが挙げられる。
また、本発明におけるバニロイド類は、バニリル基を含む化合物を含む天然物を含んでいてもよく、バニリル基を有する化合物の誘導体やさらにバニリル基に官能基を付与した合成化合物などを含んでいてもよい。
また、本発明におけるバニロイド類としては、バニリル基を含む化合物を含有するトウガラシ類を用いてもよく、バニロイド類の一部として含んでいてもよい。
トウガラシ類としては、例えば、第18改正日本薬局方に収載のトウガラシ(Capsicum annuum Linne(Solanaceae)の果実)などを好適に用いることができる。トウガラシは必要に応じてその形態を調節することができ、小片、小塊に切断若しくは破砕、又は粉末に粉砕することができ、例えば、トウガラシを粉末とした「トウガラシ末」も本発明の「トウガラシ」として用いることができる。また、トウガラシに何らかの抽出処理を施したもの(トウガラシエキス、トウガラシチンキなど)を用いてもよい。なお、トウガラシの抽出物は、抽出処理に加えて、加熱、乾燥、粉砕等の加工処理を施したものでもよい。さらに、トウガラシ類としては、トウガラシの主成分であるカプサイシノイドを用いてもよい。カプサイシノイドとしては、カプサイシン、ノナン酸バニリルアミドが好ましい。トウガラシ類としては、好ましくは、トウガラシエキス、トウガラシチンキ、ノニル酸バニリルアミド、又はカプサイシンを使用することができる。
(A-6) Vanilloids is a general term for compounds containing a vanillyl group. The vanilloids in the present invention are not particularly limited as long as they are compounds containing a vanillyl group, and examples thereof include vanillin, vanillic acid, capsaicin, vanillylmandelic acid (VMA), vanillyl butyl ether (4-butoxymethyl-2-methoxyphenol), etc.
Furthermore, the vanilloids in the present invention may include natural products containing compounds containing a vanillyl group, and may also include derivatives of compounds having a vanillyl group and synthetic compounds in which a functional group has been added to the vanillyl group.
In addition, as the vanilloids in the present invention, capsicums containing a compound containing a vanillyl group may be used, and may be included as part of the vanilloids.
As the chili peppers, for example, chili peppers (fruits of Capsicum annuum Linne (Solanaceae)) listed in the 18th revised Japanese Pharmacopoeia can be suitably used. The form of chili peppers can be adjusted as necessary, and they can be cut or crushed into small pieces or small chunks, or crushed into powder. For example, "chili pepper powder" made by powdering chili peppers can also be used as the "chili pepper" of the present invention. In addition, chili peppers that have been subjected to some kind of extraction treatment (chili pepper extract, chili pepper tincture, etc.) may be used. In addition to the extraction treatment, the chili pepper extract may be processed by heating, drying, crushing, etc. Furthermore, capsaicinoids, which are the main components of chili peppers, may be used as the chili peppers. As the capsaicinoids, capsaicin and nonanoic acid vanillylamide are preferred. As the chili peppers, chili pepper extract, chili pepper tincture, nonanoic acid vanillylamide, or capsaicin can be preferably used.
バニロイド類を使用する場合における医薬組成物におけるバニロイド類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.05~4質量%がより好ましく、0.1~2質量%が特に好ましい。
また、トウガラシ類を使用する場合における医薬組成物におけるトウガラシ類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.05~4質量%がより好ましく、0.1~2質量%が特に好ましい。
When vanilloids are used, the content of the vanilloids in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.05 to 4% by mass, and particularly preferably 0.1 to 2% by mass, based on the mass of the total amount of the pharmaceutical composition.
In addition, when capsicums are used, the content of capsicums in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10 mass%, more preferably 0.05 to 4 mass%, and particularly preferably 0.1 to 2 mass%, relative to the mass of the total amount of the pharmaceutical composition.
(A-7)ニコチン酸類としては、ニコチン酸及びその誘導体並びにそれらの塩を挙げることができる。ニコチン酸の誘導体としては、例えば、ニコチン酸エステル(具体的にはニコチン酸メチルエステル、ニコチン酸β-ブトキシエチルエステル、ニコチン酸ベンジルエステル、イノシトールヘキサニコチネート、ヘプロニカートなど)、ニコチン酸アミド、ニコチン酸アミドアデニンジヌクレオチド、ニコチン酸アミドアデニンジヌクレオチドリン酸など)などが挙げられる。ニコチン酸エステルとしては、ニコチン酸のモノエステルが好ましい。ニコチン酸類としては、ニコチン酸ベンジルエステルが好ましい。 (A-7) Examples of nicotinic acids include nicotinic acid and its derivatives and salts thereof. Examples of nicotinic acid derivatives include nicotinic acid esters (specifically, nicotinic acid methyl ester, nicotinic acid β-butoxyethyl ester, nicotinic acid benzyl ester, inositol hexanicotinate, hepronicate, etc.), nicotinamide, nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, etc.). As the nicotinic acid esters, monoesters of nicotinic acid are preferred. As the nicotinic acids, nicotinic acid benzyl ester is preferred.
ニコチン酸類を使用する場合における医薬組成物におけるニコチン酸類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.015~4質量%がより好ましく、0.02~2質量%が特に好ましい。 When nicotinic acids are used, the content of nicotinic acids in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.015 to 4% by mass, and particularly preferably 0.02 to 2% by mass, based on the total mass of the pharmaceutical composition.
(A-8)クロルフェニラミン類としては、クロルフェニラミン類およびその塩が挙げられる。クロルフェニラミンの塩としては、具体的には、マレイン酸塩、フマル酸塩等の有機酸塩;塩酸塩、硫酸塩等の無機酸塩;金属塩等の各種塩が挙げられる。クロルフェニラミン類としては、クロルフェニラミンマレイン酸塩が好ましい。 (A-8) Examples of chlorpheniramines include chlorpheniramines and their salts. Specific examples of chlorpheniramine salts include organic acid salts such as maleate and fumarate; inorganic acid salts such as hydrochloride and sulfate; and various salts such as metal salts. As the chlorpheniramines, chlorpheniramine maleate is preferred.
クロルフェニラミン類を使用する場合における医薬組成物におけるクロルフェニラミン類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.05~4質量%がより好ましく、0.1~2質量%が特に好ましい。 When chlorpheniramines are used, the content of chlorpheniramines in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.05 to 4% by mass, and particularly preferably 0.1 to 2% by mass, based on the total mass of the pharmaceutical composition.
(A-9)ジフェンヒドラミン類としては、例えば、ジフェンヒドラミンまたはその塩を挙げることができる。ジフェンヒドラミンの塩としては、塩酸塩、クエン酸塩、コハク酸塩、酒石酸塩、フマル酸塩、マレイン酸塩、ジフェニルジスルホン酸塩、タンニン酸塩、ラウリル硫酸塩、硫酸塩等の酸付加塩が挙げられる。ジフェンヒドラミン類としては、ジフェンヒドラミンまたはジフェンヒドラミン塩酸塩が好ましい。 (A-9) Examples of diphenhydramines include diphenhydramine or its salts. Examples of diphenhydramine salts include acid addition salts such as hydrochloride, citrate, succinate, tartrate, fumarate, maleate, diphenyl disulfonate, tannate, lauryl sulfate, and sulfate. As diphenhydramines, diphenhydramine or diphenhydramine hydrochloride is preferred.
ジフェンヒドラミン類を使用する場合における医薬組成物におけるジフェンヒドラミン類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.05~4質量%がより好ましく、0.1~2質量%が特に好ましい。 When diphenhydramines are used, the content of diphenhydramines in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.05 to 4% by mass, and particularly preferably 0.1 to 2% by mass, based on the total mass of the pharmaceutical composition.
(A-10)ピロリドン類としては、dl-ピロリドンカルボン酸またはその塩が挙げられ、例えば、ピロリドンカルボン酸ナトリウムが好ましい。
ピロリドン類を使用する場合における医薬組成物におけるピロリドン類の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.1~10質量%がより好ましく、1~10質量%が特に好ましい。
(A-10) Pyrrolidones include dl-pyrrolidone carboxylic acid or a salt thereof, and for example, sodium pyrrolidone carboxylate is preferred.
When pyrrolidones are used, the content of the pyrrolidones in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10 mass %, more preferably 0.1 to 10 mass %, and particularly preferably 1 to 10 mass %, based on the mass of the total amount of the pharmaceutical composition.
(A-11)無機塩は、マグネシウム又はカルシウム等のアルカリ土類金属の塩、ナトリウム又は等のアルカリ金属の塩、またはアンモニウム塩など挙げられ、例えば、塩化ナトリウム、塩化カリウム、塩化アンモニウムは好ましい。 (A-11) Examples of inorganic salts include salts of alkaline earth metals such as magnesium or calcium, salts of alkali metals such as sodium or ammonium salts, and the like. For example, sodium chloride, potassium chloride, and ammonium chloride are preferred.
無機塩を使用する場合における医薬組成物における無機塩の含有量は特に限定されないが、医薬組成物全量の質量に対して一般的には0.01~10質量%であり、0.1~10質量%がより好ましく、1~10質量%が特に好ましい。 When an inorganic salt is used, the content of the inorganic salt in the pharmaceutical composition is not particularly limited, but is generally 0.01 to 10% by mass, more preferably 0.1 to 10% by mass, and particularly preferably 1 to 10% by mass, based on the total mass of the pharmaceutical composition.
成分(A)にかかる薬物としては、好ましくは、例えば、グリチルリチン酸、グリチルレチン酸等の抗炎症剤、ジフェンヒドラミン又はその塩、クロルフェニラミンマレイン酸塩等の抗ヒスタミン剤、トコフェロール酢酸エステル、ニコチン酸ベンジルエステル等の血行改善成分、l-メントール、dl-カンフル、d-カンフル、ノナン酸バニリルアミド(ノニル酸ワニリルアミド)、トウガラシエキス、トウガラシチンキ、カプサイシン、ハッカ油、ユーカリ油、メントキシプロパンジオール (3-(メントキシ)-1,2-プロパンジオール)、3-(l-メントキシ)-2-メチルプロパン-1,2-ジオール等の局所刺激成分、アルニカチンキ等の生薬成分、イソプロピルメチルフェノール等の殺菌成分、dl-ピロリドンカルボン酸またはその塩等の湿潤剤、塩化ナトリウムなどの無機塩等を挙げることができ、これらの成分(A)は、本発明の効果を損なわない範囲で配合することができる。 Preferably, the drug for component (A) may be, for example, an anti-inflammatory agent such as glycyrrhizic acid or glycyrrhetinic acid, an antihistamine such as diphenhydramine or its salt, or chlorpheniramine maleate, a blood circulation improving component such as tocopherol acetate or nicotinic acid benzyl ester, a local irritant component such as l-menthol, dl-camphor, d-camphor, nonanoic acid vanillylamide (nonylic acid vanillylamide), capsicum extract, capsicum tincture, capsaicin, peppermint oil, eucalyptus oil, menthoxypropanediol (3-(menthoxy)-1,2-propanediol), or 3-(l-menthoxy)-2-methylpropane-1,2-diol, a herbal medicine component such as arnica tincture, a bactericidal component such as isopropylmethylphenol, a moisturizer such as dl-pyrrolidonecarboxylic acid or its salt, or an inorganic salt such as sodium chloride, and these components (A) may be blended within a range that does not impair the effects of the present invention.
上記成分以外の医薬品添加物は、例えば、経時的な含量安定性や使用感の更なる向上等を目的として必要に応じて添加するものであり、例えば、湿潤剤、保湿剤、粘稠剤、粘着剤、粘着付与樹脂、架橋剤、充填剤、油脂類、軟化剤、防腐剤、経皮吸収促進剤、安定化剤、溶解補助剤、pH調節剤、抗酸化剤、清涼化剤、界面活性剤、乳化剤、等を挙げることができる。また、本発明の医薬組成物は、その他、任意の成分を含んでいてもよい。なお、本発明の医薬組成物は、好ましくは、N-メチルピロリドン(N-メチル-2-ピロリドン)を含まない。 Pharmaceutical additives other than the above-mentioned components are added as necessary, for example, for the purpose of further improving the stability of the content over time and the feeling of use, and examples thereof include wetting agents, moisturizing agents, thickening agents, adhesives, tackifying resins, crosslinking agents, fillers, oils and fats, softeners, preservatives, transdermal absorption promoters, stabilizers, solubilizing agents, pH regulators, antioxidants, cooling agents, surfactants, emulsifiers, etc. The pharmaceutical composition of the present invention may also contain other optional components. The pharmaceutical composition of the present invention preferably does not contain N-methylpyrrolidone (N-methyl-2-pyrrolidone).
湿潤剤としては、例えば、ヒアルロン酸、dl-ピロリドンカルボン酸ナトリウムまたはその塩(例えば、dl-ピロリドンカルボン酸ナトリウム)等を用いることができる。
保湿剤としては、例えば、ソルビトール、エチレングリコール、プロピレングリコール、ポリエチレングリコール、流動パラフィン、グリセリン、マクロゴール、1,3-プロパンジオール、1,4-ブタンジオール等の多価アルコールを用いることができる。
増粘剤(粘稠剤・ゲル化剤)としては、例えば、ヒプロメロース、ヒドロキシプロピルセルロース、キサンタンガム、ゼラチン、ポリビニルアルコール、ポリビニルピロリドン、アルギン酸ナトリウム、カルボキシビニルポリマー、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム(カルメロースナトリウム)、メチルセルロース、カラギーナン、ローカストビーンガム、アルギン酸プロピレングリコール等を用いることができる。
As the wetting agent, for example, hyaluronic acid, sodium dl-pyrrolidone carboxylate or a salt thereof (eg, sodium dl-pyrrolidone carboxylate), etc. can be used.
As the moisturizing agent, for example, polyhydric alcohols such as sorbitol, ethylene glycol, propylene glycol, polyethylene glycol, liquid paraffin, glycerin, macrogol, 1,3-propanediol, and 1,4-butanediol can be used.
Examples of thickening agents (thickening agents/gelling agents) that can be used include hypromellose, hydroxypropyl cellulose, xanthan gum, gelatin, polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, carboxyvinyl polymer, carboxymethyl cellulose, sodium carboxymethyl cellulose (carmellose sodium), methyl cellulose, carrageenan, locust bean gum, and propylene glycol alginate.
粘着剤としては、例えば、アクリル酸・アクリル酸オクチルエステル共重合体、アクリル酸エステル・酢酸ビニル共重合体、アクリル酸2-エチルヘキシル・ビニルピロリドン共重合体溶液、アクリル酸2-エチルヘキシル・メタクリル酸2-エチルヘキシル・メタクリル酸ドデシル共重合体溶液、アクリル酸エチル・メタクリル酸メチルコポリマー分散液、アクリル酸メチル・アクリル酸2-エチルヘキシル共重合体樹脂エマルジョン、アクリル樹脂アルカノールアミン溶液、メタクリル酸・アクリル酸n-ブチルコポリマー、アクリル酸シルクフィブロイン共重合樹脂、アクリル酸デンプン300、アクリル酸デンプン1000、アクリル酸ブチル・メタクリル酸2-エチルヘキシル・ジアセトンアクリルアミド共重合体、アクリル酸ブチル・メタクリル酸2-ヒドロキシエチル・ジアセトンアクリルアミド共重合体、アクリル酸ブチル・アクリル酸エチル・メタクリル酸2-ヒドロキシエチル・ジアセトンアクリルアミド共重合体、アクリル酸ブチル・アクリル酸2-エチルヘキシル・メタクリル酸2-ヒドロキシエチル・ジアセトンアクリルアミド共重合体、アクリル酸イソノニル・メタクリル酸2-ヒドロキシエチル・ジアセトンアクリルアミド共重合体、アクリル酸2-エチルヘキシル・メタクリル酸2-ヒドロキシエチル・ジアセトンアクリルアミド共重合体、アクリル酸ブチル・アクリル酸エチル・メタクリル酸3-ヒドロキシプロピル・メタクリル酸2-ヒドロキシエチル・ジアセトンアクリルアミド共重合体、アクリル酸ブチル・アクリル酸エチル・メタクリル酸3-ヒドロキシプロピル・ジアセトンアクリルアミド共重合体等のアクリル系粘着剤;シスイソプレンゴム、スチレンイソプレンゴム、シスポリイソプレンゴム、ハイシスポリイソプレンゴム、スチレンブタジエンゴム(SBR)、スチレン・イソプレン・スチレンブロック共重合体(SIS)、スチレン・ブタジエン・スチレンブロック共重合体(SBS)、ポリイソプレン、ポリイソブチレン(PIB)、クロロプレンゴム、ポリブテン、天然ゴムラテックス、SBR合成ラテックス等の合成ゴム系粘着剤;ポリジメチルシロキサン、ポリメチルビニルシロキサン、ポリメチルフェニルシロキサン等のシリコーン系粘着剤の他、ポリアクリル酸、ポリアクリル酸ナトリウム、ポリアクリル酸部分中和物、N-ビニルアセトアミド・アクリル酸ナトリウム共重合体、ポリビニルアルコール、ポリビニルピロリドン、ヒドロキシメチルセルロース、カルボキシメチルセルロースナトリウム、アルギン酸、アルギン酸ナトリウム、ゼラチン、グァーガム、トラガントガム、アラビアゴム等に加えて、これらをアルミニウム、亜鉛、マグネシウム、カルシウム等の金属塩で架橋したもの等を用いることができる。 Examples of adhesives include acrylic acid/octyl acrylate copolymer, acrylic ester/vinyl acetate copolymer, 2-ethylhexyl acrylate/vinylpyrrolidone copolymer solution, 2-ethylhexyl acrylate/2-ethylhexyl methacrylate/dodecyl methacrylate copolymer solution, ethyl acrylate/methyl methacrylate copolymer dispersion, methyl acrylate/2-ethylhexyl acrylate copolymer resin emulsion, acrylic resin alkanolamine solution, methacrylic acid/n-butyl acrylate copolymer, acrylic acid silk fibroin copolymer resin, starch acrylate 300, starch acrylate 1000, butyl acrylate, butyl acrylate, 2-ethylhexyl methacrylate, diacetone acrylamide copolymer, butyl acrylate, 2-hydroxyethyl methacrylate, diacetone acrylamide copolymer, butyl acrylate, ethyl acrylate, 2-hydroxyethyl methacrylate, diacetone acrylamide copolymer, butyl acrylate, 2-ethylhexyl acrylate, 2-hydroxyethyl methacrylate, diacetone acrylamide copolymer, isononyl acrylate, 2-hydroxyethyl methacrylate, diacetone acrylamide copolymer, 2-ethylhexyl acrylate, 2-hydroxyethyl methacrylate, diacetone acrylamide copolymer, butyl acrylate, Acrylic adhesives such as ethyl acrylate, 3-hydroxypropyl methacrylate, 2-hydroxyethyl methacrylate, and diacetone acrylamide copolymers, and butyl acrylate, ethyl acrylate, 3-hydroxypropyl methacrylate, and diacetone acrylamide copolymers; cis-isoprene rubber, styrene-isoprene rubber, cis-polyisoprene rubber, high-cis-polyisoprene rubber, styrene-butadiene rubber (SBR), styrene-isoprene-styrene block copolymers (SIS), styrene-butadiene-styrene block copolymers (SBS), polyisoprene, polyisobutylene (PIB), chloroprene rubber, polybutene, and natural rubber latex Synthetic rubber adhesives such as synthetic rubber cellulose and synthetic SBR latex; silicone adhesives such as polydimethylsiloxane, polymethylvinylsiloxane, and polymethylphenylsiloxane; polyacrylic acid, sodium polyacrylate, partially neutralized polyacrylic acid, N-vinylacetamide-sodium acrylate copolymer, polyvinyl alcohol, polyvinylpyrrolidone, hydroxymethylcellulose, sodium carboxymethylcellulose, alginic acid, sodium alginate, gelatin, guar gum, tragacanth gum, gum arabic, and the like, as well as those crosslinked with metal salts such as aluminum, zinc, magnesium, and calcium can also be used.
粘着付与樹脂としては、例えば、ロジン、水素添加ロジングリセリンエステル、エステルガム、マレイン酸レジン、マレイン化ロジングリセリンエステル、テルペン樹脂、石油樹脂、脂環族飽和炭化水素樹脂、脂肪族炭化水素樹脂等を用いることができる。
架橋剤としては、例えば、乾燥水酸化アルミニウムゲル、水酸化アルミニウムマグネシウム、ケイ酸アルミン酸マグネシウム、メタケイ酸アルミン酸マグネシウム、合成ヒドロサルタイト、ジヒドロキシアルミニウムアミノアセテート等を用いることができる。
充填剤としては、例えば、アルミナ、カオリン、ベントナイト、酸化亜鉛、酸化アルミニウム、酸化チタン、合成ケイ酸アルミニウム、酸化マグネシウム、酸化鉄、ステアリン酸亜鉛、亜鉛酸カルシウム、タルク、炭酸カルシウム、シリカ(二酸化ケイ素)等を用いることができる。
油脂類としては、例えば、スクワラン、パラフィン、流動パラフィン、軽質流動パラフィン、ワセリン、ゲル化炭化水素等の炭化水素類;ミリスチン酸イソプロピル、ミリスチン酸オクチルドデシル等の脂肪酸エステル類;べへニルアルコール、ラウリルアルコール、ミリスチルアルコール、セチルアルコール、ステアリルアルコール、イソステアリルアルコール、オレイルアルコール等の高級アルコール類;ベヘニン酸、ラウリン酸、ミリスチン酸、ステアリン酸、イソステアリン酸、オレイン酸等の高級脂肪酸;カルナウバロウ、鯨ロウ、セラック、ホホバ油、ミツロウ、サラシミツロウ、モンタンロウ、ラノリン、精製ラノリン、還元ラノリン等のロウ類;シリコーン油等を用いることができる。
Examples of tackifying resins that can be used include rosin, hydrogenated rosin glycerin ester, ester gum, maleic acid resin, maleated rosin glycerin ester, terpene resin, petroleum resin, alicyclic saturated hydrocarbon resin, and aliphatic hydrocarbon resin.
As the crosslinking agent, for example, dried aluminum hydroxide gel, aluminum magnesium hydroxide, magnesium aluminosilicate, magnesium aluminometasilicate, synthetic hydrosaltite, dihydroxyaluminum aminoacetate, etc. can be used.
Examples of the filler that can be used include alumina, kaolin, bentonite, zinc oxide, aluminum oxide, titanium oxide, synthetic aluminum silicate, magnesium oxide, iron oxide, zinc stearate, calcium zincate, talc, calcium carbonate, and silica (silicon dioxide).
Examples of fats and oils that can be used include hydrocarbons such as squalane, paraffin, liquid paraffin, light liquid paraffin, petrolatum, and gelled hydrocarbons; fatty acid esters such as isopropyl myristate and octyldodecyl myristate; higher alcohols such as behenyl alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, and oleyl alcohol; higher fatty acids such as behenic acid, lauric acid, myristic acid, stearic acid, isostearic acid, and oleic acid; waxes such as carnauba wax, spermaceti, shellac, jojoba oil, beeswax, white beeswax, montan wax, lanolin, refined lanolin, and reduced lanolin; and silicone oils.
軟化剤としては、例えば、パラフィン系プロセスオイル、ナフテン系プロセスオイル及び芳香族系プロセスオイル等の石油系オイル;スクワラン;スクワレン;綿実油、パーム油、ヤシ油、アーモンド油、ナタネ油、オリーブ油、ツバキ油、ヒマシ油、トール油及びラッカセイ油等の植物系オイル;シリコンオイル;ジブチルフタレート及びジオクチルフタレートなどの二塩基酸エステル;ポリブテン及び液状イソプレンゴム等の液状ゴム;ミリスチン酸イソプロピル、ラウリン酸ヘキシル、セバシン酸ジエチル及びセバシン酸ジイソプロピル等の液状脂肪酸エステル類;ジエチレングリコール;ポリエチレングリコール;プロピレングリコール;ジプロピレングリコール;トリアセチン;クエン酸トリエチル;クロタミトン;グリセリン等を用いることができる。 As softeners, for example, petroleum-based oils such as paraffin-based process oil, naphthenic process oil, and aromatic process oil; squalane; squalene; vegetable oils such as cottonseed oil, palm oil, coconut oil, almond oil, rapeseed oil, olive oil, camellia oil, castor oil, tall oil, and peanut oil; silicone oil; dibasic acid esters such as dibutyl phthalate and dioctyl phthalate; liquid rubbers such as polybutene and liquid isoprene rubber; liquid fatty acid esters such as isopropyl myristate, hexyl laurate, diethyl sebacate, and diisopropyl sebacate; diethylene glycol; polyethylene glycol; propylene glycol; dipropylene glycol; triacetin; triethyl citrate; crotamiton; glycerin, etc. can be used.
防腐剤としては、例えば、パラオキシ安息香酸メチル、パラオキシ安息香酸エチル、パラオキシ安息香酸プロピル、パラオキシ安息香酸イソプロピル、パラオキシ安息香酸ブチル、パラオキシ安息香酸イソブチル、パラオキシ安息香酸ベンジル、安息香酸ナトリウム、安息香酸、安息香酸ベンジル、塩化ベンザルコニウム、塩化セチルピリジニウム、塩化ベンゼトニウム、アミノエチルスルホン酸等を用いることができる。
経皮吸収促進剤としては、例えば、アルコール、脂肪酸、アジピン酸ジイソプロピル等の脂肪酸エステル、脂肪酸エーテル、乳酸エステル、酢酸エステル、テルペン系化合物、ピロリドン誘導体、有機酸、有機酸エステル、精油、炭化水素、炭化プロピレン、エイゾン又はその誘導体等を用いることができる。
安定化剤としては、例えば、オキシベンゾン、ジブチルヒドロキシトルエン(BHT)、エデト酸ナトリウム、UV吸収剤(例えば、ジベンゾイルメタン誘導体)等を用いることができる。
Examples of preservatives that can be used include methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, isopropyl parahydroxybenzoate, butyl parahydroxybenzoate, isobutyl parahydroxybenzoate, benzyl parahydroxybenzoate, sodium benzoate, benzoic acid, benzyl benzoate, benzalkonium chloride, cetylpyridinium chloride, benzethonium chloride, and aminoethylsulfonic acid.
Examples of the percutaneous absorption enhancer that can be used include alcohols, fatty acids, fatty acid esters such as diisopropyl adipate, fatty acid ethers, lactate esters, acetate esters, terpene compounds, pyrrolidone derivatives, organic acids, organic acid esters, essential oils, hydrocarbons, propylene carbonate, azone or derivatives thereof, and the like.
As the stabilizer, for example, oxybenzone, dibutylhydroxytoluene (BHT), sodium edetate, UV absorbers (for example, dibenzoylmethane derivatives), etc. can be used.
溶解補助剤としては、例えば、ベンジルアルコール;ピロチオデカン;ミリスチン酸イソプロピル;クロタミトン;N-メチル-2-ピロリドン等のピロリドン類;高級アルコール類;アジピン酸ジエチル、アジピン酸イソプロピル、アジピン酸ジイソプロピル、アジピン酸ジイソブチル、アジピン酸ジオクチル、アジピン酸ジ(2-ヘプチルウンデシル)、セバシン酸ジイソプロピル、セバシン酸ジエチル等の多塩基酸類;ポリエチレングリコール(PEG)、ポリブチレングリコール等のポリアルキレングリコール;モノステアリン酸ポリエチレングリコール等のオキシアルキレン脂肪酸エステル等を用いることができる。
pH調節剤としては、例えば、塩酸、水酸化ナトリウム、水酸化カリウム、クエン酸、リンゴ酸、酒石酸、グルコン酸、乳酸、有機酸、有機アミン(例えば、トリエタノールアミン、ジイソプロパノールアミンなど)、リン酸等を用いることができる。
抗酸化剤としては、例えば、アスコルビン酸、パルミチン酸アスコルビン酸、亜硫酸水素ナトリウム、乾燥亜硫酸ナトリウム、ピロ亜硫酸ナトリウム、エデト酸ナトリウム、クエン酸水和物、無水クエン酸、クエン酸、クエン酸ナトリウム、酢酸トコフェロール、dI-αートコフェロール、ジクロルイソシアヌル酸カリウム、ジブチルヒドロキシトルエン、ブチルヒドロキシアニソール、プチルヒドロキシアニソール、大豆レシチン、ペンタエリスリルーテトラキス[3一(3,5-ジーt-ブチルー4-ヒドロキシフエニル)プロピオネート]、2-メルカプトベンズイミダゾール、ベンゾトリアゾール、没食子酸プロピル等を用いることができる。
清涼化剤としては、例えば、l-メントール、カンフル、dl-カンフル、ハッカ油、ユーカリ油、チモール等を挙げることができる。
Examples of the solubilizing agent that can be used include benzyl alcohol; pyrrothiodecane; isopropyl myristate; crotamiton; pyrrolidones such as N-methyl-2-pyrrolidone; higher alcohols; polybasic acids such as diethyl adipate, isopropyl adipate, diisopropyl adipate, diisobutyl adipate, dioctyl adipate, di(2-heptylundecyl) adipate, diisopropyl sebacate, and diethyl sebacate; polyalkylene glycols such as polyethylene glycol (PEG) and polybutylene glycol; and oxyalkylene fatty acid esters such as polyethylene glycol monostearate.
Examples of pH adjusters that can be used include hydrochloric acid, sodium hydroxide, potassium hydroxide, citric acid, malic acid, tartaric acid, gluconic acid, lactic acid, organic acids, organic amines (e.g., triethanolamine, diisopropanolamine, etc.), phosphoric acid, and the like.
Examples of antioxidants that can be used include ascorbic acid, ascorbic acid palmitate, sodium hydrogen sulfite, dried sodium sulfite, sodium pyrosulfite, sodium edetate, citric acid hydrate, anhydrous citric acid, citric acid, sodium citrate, tocopherol acetate, dI-α-tocopherol, potassium dichloroisocyanurate, dibutylhydroxytoluene, butylhydroxyanisole, butylhydroxyanisole, soybean lecithin, pentaerythryl-tetrakis[3-(3,5-di-t-butyl-4-hydroxyphenyl)propionate], 2-mercaptobenzimidazole, benzotriazole, and propyl gallate.
Examples of the cooling agent include l-menthol, camphor, dl-camphor, peppermint oil, eucalyptus oil, and thymol.
界面活性剤としては、非イオン性界面活性剤を用いてもよく、イオン性界面活性剤を用いてもよい。 As the surfactant, a nonionic surfactant or an ionic surfactant may be used.
非イオン性界面活性剤としては、例えば、プロピレングリコールモノ脂肪酸エステル、エチレングリコールモノ脂肪酸エステル、グリセリンモノ脂肪酸エステル、ポリグリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、ショ糖脂肪酸エステル、メチルグルコシド脂肪酸エステル、アルキルポリグルコシド、ポリエチレングリコール脂肪酸エステル等の多価アルコール脂肪酸エステル又は多価アルコールアルキルエーテル;ポリオキシエチレンアルキルエーテル、ポリオキシエチレンアルキルフェニルエーテル、ポリオキシエチレンフィトステロール、ポリオキシエチレンフィトスタノール、ポリオキシエチレンポリオキシプロピレンアルキルエーテル等のポリオキシエチレンエーテル;ポリオキシエチレンモノ脂肪酸エステル、ポリエチレングリコールジ脂肪酸エステル、ポリオキシエチレングリセリン脂肪酸エステル、ポリソルベート20、ポリソルベート40、ポリソルベート60、ポリソルベート65、ポリソルベート80等のポリオキシエチレンソルビタン脂肪酸エステル、ポリオキシエチレンソルビトール脂肪酸エステル、ポリオキシエチレンメチルグルコシド脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油20、ポリオキシエチレン硬化ヒマシ油40、ポリオキシエチレン硬化ヒマシ油50、ポリオキシエチレン硬化ヒマシ油60等のポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンヒマシ油、ポリオキシエチレン植物油、ポリオキシエチレンアルキルエーテル脂肪酸エステル、ポリオキシエチレンポリオキシプロピレングリコール等のエーテルエステル等の非イオン性界面活性剤;ラウリル硫酸ナトリウム、セチル硫酸ナトリウムなどのイオン性界面活性剤;オクチルドデカノール等の高級アルコールなどが挙げられる。本発明におけるポリオキシエチレンアルキルエーテルは、例えば、ポリオキシエチレンラウリルエーテル、ポリオキシエチレンセチルエーテル、ポリオキシエチレンステアリルエーテル、ポリオキシエチレンオレイルエーテル、ポリオキシエチレンベヘニルエーテル等を挙げることができる。 Examples of nonionic surfactants include polyhydric alcohol fatty acid esters or polyhydric alcohol alkyl ethers such as propylene glycol mono fatty acid esters, ethylene glycol mono fatty acid esters, glycerin mono fatty acid esters, polyglycerin fatty acid esters, sorbitan fatty acid esters, sucrose fatty acid esters, methyl glucoside fatty acid esters, alkyl polyglucosides, and polyethylene glycol fatty acid esters; polyoxyethylene ethers such as polyoxyethylene alkyl ethers, polyoxyethylene alkylphenyl ethers, polyoxyethylene phytosterols, polyoxyethylene phytostanols, and polyoxyethylene polyoxypropylene alkyl ethers; polyoxyethylene mono fatty acid esters, polyethylene glycol di fatty acid esters, and polyoxyethylene glycerin fatty acid esters; Examples of the polyoxyethylene sorbitan fatty acid esters include polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 65, and polysorbate 80; polyoxyethylene sorbitol fatty acid esters; polyoxyethylene methyl glucoside fatty acid esters; polyoxyethylene hydrogenated castor oils such as polyoxyethylene hydrogenated castor oil 20, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 50, and polyoxyethylene hydrogenated castor oil 60; polyoxyethylene castor oil; polyoxyethylene vegetable oils; polyoxyethylene alkyl ether fatty acid esters; and nonionic surfactants such as ether esters such as polyoxyethylene polyoxypropylene glycol; ionic surfactants such as sodium lauryl sulfate and sodium cetyl sulfate; and higher alcohols such as octyldodecanol. Examples of the polyoxyethylene alkyl ethers in the present invention include polyoxyethylene lauryl ether, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene oleyl ether, and polyoxyethylene behenyl ether.
本発明におけるポリオキシエチレンポリオキシプロピレンアルキルエーテルは、例えば、ポリオキシエチレンポリオキシプロピレンセチルエーテル等を挙げることができる。
本発明におけるポリオキシエチレンポリオキシプロピレンアルキルエーテルは、例えば、モノラウリン酸ポリエチレングリコール、モノステアリン酸ポリエチレングリコール、モノオレイン酸ポリエチレングリコール等を挙げることができる。
The polyoxyethylene polyoxypropylene alkyl ether in the present invention may, for example, be polyoxyethylene polyoxypropylene cetyl ether.
Examples of the polyoxyethylene polyoxypropylene alkyl ether in the present invention include polyethylene glycol monolaurate, polyethylene glycol monostearate, and polyethylene glycol monooleate.
本発明における非イオン性界面活性剤は、医薬品添加物事典2021に収載されている。 The nonionic surfactants used in the present invention are listed in the Pharmaceutical Additives Encyclopedia 2021.
イオン性界面活性剤としては、例えば、ステアリン酸ナトリウム、ステアリン酸カリウム、セチル硫酸ナトリウム、ポリオキシエチレンラウリルエーテルリン酸ナトリウム、ジオクチルソジウムスルホサクシネート等のアニオン界面活性剤、塩化ベンザルコニウム、塩化ベンゼトニウム等のカチオン界面活性剤が挙げられる。 Examples of ionic surfactants include anionic surfactants such as sodium stearate, potassium stearate, sodium cetyl sulfate, sodium polyoxyethylene lauryl ether phosphate, and dioctyl sodium sulfosuccinate, and cationic surfactants such as benzalkonium chloride and benzethonium chloride.
本発明におけるイオン性界面活性剤は、医薬品添加物事典2021、第18改正日本薬局方に収載されている。
本発明における乳化剤は、例えば、上記各種界面活性剤、上記高級アルコールなどで挙げたものを任意に用いてもよい。
本発明におけるその他の任意の成分としては、例えば、トラネキサム酸、カンゾウなどの生薬等が挙げられる。
具体的に、本発明のロキソプロフェン又はその塩およびサリチル酸類を含有する医薬組成物においては、さらにトラネキサム酸およびカンゾウのうち少なくとも1つを含んでいてもよい。
The ionic surfactant of the present invention is listed in the Pharmaceutical Additives Encyclopedia 2021 and the 18th Revised Edition of the Japanese Pharmacopoeia.
As the emulsifier in the present invention, for example, any of the above-mentioned various surfactants and higher alcohols may be used.
Other optional ingredients in the present invention include, for example, herbal medicines such as tranexamic acid and licorice.
Specifically, the pharmaceutical composition of the present invention containing loxoprofen or a salt thereof and a salicylic acid may further contain at least one of tranexamic acid and licorice.
本発明の医薬組成物の具体的な剤形としては、例えば、外用液剤、軟膏剤、クリーム剤、スプレー剤(外用エアゾール剤、ポンプスプレー剤)、ゲル剤、貼付剤(テープ剤、パップ剤)、又は外用固形剤等を挙げることができ、各剤形に適した添加剤や基剤を適宜使用し、第18改正日本薬局方などに記載される通常の方法に従い、製造することができる。本発明における医薬組成物の剤形としては、外用液剤が特に好ましい。本発明において、パップ剤やテープ剤のような貼付剤を作成する場合には、膏体量によってロキソプロフェン又はその塩(例えば、ロキソプロフェンナトリウム)の濃度が変動することがあるが、適切なロキソプロフェン又はその塩(例えば、ロキソプロフェンナトリウム)の濃度となるように適宜膏体量等を調整すればよい。 Specific dosage forms of the pharmaceutical composition of the present invention include, for example, liquid for external use, ointment, cream, spray (aerosol for external use, pump spray), gel, patch (tape, cataplasm), or solid for external use. Each dosage form can be produced by using appropriate additives and bases suitable for the dosage form, according to the usual method described in the 18th edition of the Japanese Pharmacopoeia, etc. As the dosage form of the pharmaceutical composition of the present invention, liquid for external use is particularly preferred. In the present invention, when preparing a patch such as a cataplasm or tape, the concentration of loxoprofen or a salt thereof (e.g., loxoprofen sodium) may vary depending on the amount of ointment, but the amount of ointment, etc. may be appropriately adjusted to obtain an appropriate concentration of loxoprofen or a salt thereof (e.g., loxoprofen sodium).
また、本発明の医薬組成物の製剤は、例えば、ガラス製の容器・包装、又は、アルミニウム等の金属製の容器・包装、又は、ポリエチレン、ポリプロピレン等のオレフィン系樹脂製の容器・包装に収容し、密封することができる。また、容器・包装には、再生プラスチックやバイオマス原料など環境に配慮された原料・材料を含む容器・包装を用いてもよく、必要に応じ、ラミネート構造の材料やガスバリア材料、高温環境などの際の熱や光など、医薬品の容器・包装の外部からの因子・要素・環境変化による医薬組成物の劣化を防ぎ、適切に医薬組成物の品質が保持されるような任意の材料などを用いてもよい本発明の一実施形態においては、適切な容器・包装に皮膚外用剤の製剤・組成物が収容された医薬品としてもよい。ガスバリア材料としては、特に限定されないが、例えば、凸版印刷株式会社製「GL FILM」などが挙げられる。
本発明の医薬組成物によれば、サリチル酸類とロキソプロフェン又はその塩を配合することによって、抗炎症作用を向上させることができる。また、本発明の医薬組成物によれば、サリチル酸類とロキソプロフェン又はその塩を配合することによって、抗炎症作用を持続させることができる。
In addition, the pharmaceutical composition formulation of the present invention can be housed and sealed in, for example, a glass container/package, or a metal container/package such as aluminum, or an olefin resin container/package such as polyethylene or polypropylene. In addition, the container/package may be made of environmentally friendly raw materials such as recycled plastics or biomass raw materials, and if necessary, any material that prevents deterioration of the pharmaceutical composition due to factors, elements, or environmental changes from outside the pharmaceutical container/package, such as heat or light in a high-temperature environment, and appropriately maintains the quality of the pharmaceutical composition, may be used. In one embodiment of the present invention, the pharmaceutical may be a pharmaceutical in which a formulation/composition of a skin topical agent is housed in an appropriate container/package. The gas barrier material is not particularly limited, but examples thereof include "GL FILM" manufactured by Toppan Printing Co., Ltd.
According to the pharmaceutical composition of the present invention, the anti-inflammatory effect can be improved by blending salicylic acids with loxoprofen or a salt thereof. Also, according to the pharmaceutical composition of the present invention, the anti-inflammatory effect can be sustained by blending salicylic acids with loxoprofen or a salt thereof.
本発明は、一実施形態として、サリチル酸類を、ロキソプロフェン又はその塩の抗炎症作用の増強剤として使用してもよい。
本発明は、一実施形態として、サリチル酸類を、ロキソプロフェン又はその塩の抗炎症作用の持続剤として使用してもよい 。
In one embodiment of the present invention, a salicylic acid may be used as an enhancer for the anti-inflammatory effect of loxoprofen or a salt thereof.
In one embodiment of the present invention, a salicylic acid may be used as an agent for sustaining the anti-inflammatory action of loxoprofen or a salt thereof.
以下に、実施例をあげて本発明を更に具体的に説明するが、本発明はこれら実施例に何ら限定されるものではない。 The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these examples.
<試験材料>
(1)被験物質
無水エタノールと水とジイソプロパノールアミンとリンゴ酸とを混合し、pH調節剤(乳酸)を加えてpHを6.5程度に調節した溶液を基剤とした(以下のA:基剤「無水エタノール38質量%+ジイソプロパノールアミン3質量%+リンゴ酸1質量%+水、乳酸適量」)。
また、B~Dの各群でも、同様の基剤を用い、乳酸を用いてpHを6.5程度に調整し、B~Dのそれぞれに示す組成にて各溶液を調製した。
A:基剤(無水エタノール38質量%+ジイソプロパノールアミン3質量%+リンゴ酸1質量%+水、乳酸適量)
B:ロキソプロフェンナトリウム水和物(LOX,無水物として0.5質量%とした溶液)
C:ロキソプロフェンナトリウム水和物(LOX,無水物として1.0質量%とした溶液)
D:LOX(0.5質量%)+サリチル酸グリコール(GS,5.0質量%)(Lox 0 .5質量%、サリチル酸グリコール5.0質量%とした溶液)
<Test materials>
(1) Test substance: A solution prepared by mixing absolute ethanol, water, diisopropanolamine, and malic acid and adding a pH adjuster (lactic acid) to adjust the pH to about 6.5 was used as a base (A below: base "38% by weight absolute ethanol + 3% by weight diisopropanolamine + 1% by weight malic acid + water, appropriate amount of lactic acid").
In each of groups B to D, the same base was used, and the pH was adjusted to about 6.5 using lactic acid to prepare solutions with the compositions shown for each group B to D.
A: Base (38% by weight of absolute ethanol + 3% by weight of diisopropanolamine + 1% by weight of malic acid + water, appropriate amount of lactic acid)
B: Loxoprofen sodium hydrate (LOX, 0.5% by mass solution as anhydrous)
C: Loxoprofen sodium hydrate (LOX, 1.0% by mass solution as anhydrous)
D: LOX (0.5% by mass) + glycol salicylate (GS, 5.0% by mass) (a solution containing 0.5% by mass of Lox and 5.0% by mass of glycol salicylate)
(2)試薬
λ-Carrageenan(以下カラゲニンと記載):東京化成工業(株)
日本薬局方生理食塩液(大塚生食注) 株式会社大塚製薬工場
イソフルラン マイラン製薬(株)
(2) Reagent λ-Carrageenan (hereinafter referred to as carrageenan): Tokyo Chemical Industry Co., Ltd.
Japanese Pharmacopoeia Physiological Saline Solution (Otsuka Normal Saline Injection) Otsuka Pharmaceutical Factory, Inc. Isoflurane Mylan Pharmaceuticals Co., Ltd.
(3)使用動物
(一財)動物繁殖研究所より,ラット,Iar:Wistar-Imamichi(SPF),4週齢の雄を入手した。動物は入荷日に耳パンチ法により個体を識別した。ただし、動物は入荷から群分け日までを馴化期間とし、入荷日を0日として7日まで検疫期間とした。一般状態観察は毎日行った。
(3) Animals used
Four-week-old male rats (Iar:Wistar-Imamichi (SPF)) were obtained from the Animal Reproduction Institute (Incorporated Foundation). On the day of arrival, the animals were individually identified by ear punching. However, the acclimatization period for the animals was from arrival to the day of grouping, and the quarantine period was from the day of arrival to the 7th day, with the day of arrival being considered as day 0. General observations were conducted daily.
(4)飼育方法
動物は温度22±3℃(実測値:21.2~23.6℃)、湿度50±20%(実測値:42.6~53.0%)、換気回数13~17回/時間(HEPAフィルターで濾過したオールフレッシュ方式)、照明時間8:00~20:00(明12時間,暗12時間)の設定環境下の飼育室内で、ステンレス製可動ラック(1790W×470D×1650H mm)に装着したステンレス製金網2連ケージの1区画(255W×185D×200H mm)に個別に収容した。飼料は,ステンレス製固型飼料給餌器により固型飼料ラボMRストック(日本農産工業(株))を舐め防止フードの装着時を除き自由に与えた。飲料水は、ポリサルフォン製給水器(先管ステンレス製)により舐め防止フードの装着時を除き自由に与えた。
(4) Rearing method The animals were individually housed in a section (255W×185D×200H mm) of a stainless steel mesh double cage attached to a stainless steel movable rack (1790W×470D×1650H mm) in a rearing room with a temperature of 22±3°C (actual value: 21.2-23.6°C), humidity of 50±20% (actual value: 42.6-53.0%), ventilation rate of 13-17 times/hour (all-fresh method filtered with a HEPA filter), and lighting time of 8:00-20:00 (12 hours light, 12 hours dark). The animals were fed solid feed Lab MR Stock (Nosan Corporation) from a stainless steel solid feeder ad libitum, except when the lick-prevention hood was worn. Drinking water was provided ad libitum from a polysulfone waterer (stainless steel tip) except when the lick-prevention hood was worn.
<試験方法>
(1)体重測定、足蹠容積測定及び群分け
検疫・馴化期間の終了した5週齢のラットの体重を測定した後,右後肢足蹠容積をラット用足蹠容積測定装置を用いて測定し、足蹠容積を指標として、層別連続無作為化法により次の群構成表に基づき群分けを行った。
<Test Method>
(1) Body weight measurement, footpad volume measurement, and group allocation After the quarantine and acclimation period, the body weight of 5-week-old rats was measured, and the right hind footpad volume was measured using a rat footpad volume measuring device. Using the footpad volume as an index, the rats were assigned to groups according to the following group composition table by a stratified sequential randomization method.
a)液剤について,100 mg相当の容量(μL)を事前に確認した.
b)有効成分(LOXは無水物として)の量を示す.
c)単回投与とし,投与1時間後に投与部位を清拭し,投与終了とした.
a) For liquid preparations, the volume (μL) equivalent to 100 mg was confirmed in advance.
b) The amount of active ingredient (LOX as anhydrous substance) is indicated.
c) A single dose was administered, and the administration site was wiped one hour after administration, at which point administration was completed.
(2)被験物質及び起炎物質の調製
被験物質を必要量分取し、そのまま投与に使用した。
起炎物質として、0.5%カラゲニン生理食塩溶液を調製した。分析用電子天びんを用いてカラゲニンを0.1g秤量後スターラー及び回転子を用いて撹拌させた生理食塩液に加えてそのまま一夜撹拌を継続し、生理食塩液を加え全量を20 mLとした。投与前日より調製し、残余起炎物質は大量の水道水で希釈し廃棄した。
(2) Preparation of test substance and inflammatory substance A required amount of the test substance was dispensed and used as it was for administration.
A 0.5% carrageenan solution in saline was prepared as an inflammatory substance. 0.1 g of carrageenan was weighed out using an analytical electronic balance, added to saline solution stirred with a stirrer and a rotor, and stirred overnight. Saline was added to make the total volume 20 mL. The remaining inflammatory substance was diluted with a large amount of tap water and discarded the remaining solution the day before administration.
(3)被験物質の投与方法
ピペットマンを用いて、被験物質を右後肢足首より先端側の足根骨関節部位に足の甲側から足底側に均一になるように、右後肢足蹠全体に塗布した。次に,2.5×2.8 cmのガーゼで塗布部位を覆い、伸縮性ネット包帯で固定後、サージカルテープで留めた。更に、被験物質の塗布中は、被験物質の経口摂取を防ぐため舐め防止フードを被せた。
(3) Method of administering the test substance Using a pipette, the test substance was applied to the entire right hind paw at the tarsal joint on the distal side of the ankle, evenly from the instep to the plantar side. The application site was then covered with 2.5 x 2.8 cm gauze, fixed with an elastic net bandage, and secured with surgical tape. Furthermore, a lick-prevention hood was placed over the area during application of the test substance to prevent oral ingestion of the test substance.
(4)被験物質の投与回数及び投与時間
単回投与とし,投与時間は1時間とした.投与時間が経過した直後に,微温湯に浸した脱脂綿で投与部位を清拭し投与終了とした。
(4) Number of doses and duration of administration of the test substance A single dose was administered, and the administration duration was 1 hour. Immediately after the administration time had elapsed, the administration site was wiped with absorbent cotton soaked in lukewarm water, and administration was completed.
(5)起炎物質の投与
26Gの注射針を装着した注射筒に充填した0.5%カラゲニン生理食塩溶液0.1 mLを右後肢足蹠皮下に投与した。
(5) Administration of inflammatory substances
0.1 mL of 0.5% carrageenan in physiological saline solution filled in a syringe equipped with a 26G needle was administered subcutaneously into the right hind footpad.
(6)右後肢足蹠容積の測定
被験物質投与前、起炎物質投与後3,4及び5時間に、ラット用足蹠容積測定装置を用いて右後肢足蹠容積を測定した。
(6) Measurement of right hind paw volume Before administration of the test substance, and 3, 4, and 5 hours after administration of the inflammatory substance, the right hind paw volume was measured using a rat paw volume measuring device.
(7)浮腫率及び浮腫率総和の算出
得られた足蹠容積より,次式により浮腫率及び浮腫率総和を算出した.
(7) Calculation of edema rate and sum of edema rates The edema rate and sum of edema rates were calculated from the obtained paw volume using the following formula.
<結果>
浮腫率および浮腫率総和を表2に示し、浮腫率総和を図1に示す。
その結果、LOX(0.5質量%)+サリチル酸グリコール(5.0質量%)の浮腫率総和においてLOX(1.0質量%)と同程度の値を示し、サリチル酸グリコールはロキソプロフェンの抗炎症作用を増強する作用を有することが示された。
また、各時間ごとの浮腫率(%)において、LOX(0.5質量%)+サリチル酸グリコール(5.0質量%)(D群:LOX+サリチル酸グリコール)は、LOX(1.0質量%)(C群:LOX高)と比較すると、5時間後の浮腫抑制率が特に優れていた。このように、LOX(0.5質量%)+サリチル酸グリコール(5.0質量%)(D群:LOX+サリチル酸グリコール)は、抗炎症作用を持続させる(LOXの作用を維持する)効果があることが示された。
<Results>
The edema rate and the sum of the edema rates are shown in Table 2, and the sum of the edema rates is shown in FIG.
As a result, the sum of the edema rates for LOX (0.5% by mass) and glycol salicylate (5.0% by mass) was similar to that for LOX (1.0% by mass), demonstrating that glycol salicylate has the effect of enhancing the anti-inflammatory effect of loxoprofen.
In addition, in terms of the edema rate (%) at each time point, LOX (0.5% by mass) + glycol salicylate (5.0% by mass) (Group D: LOX + glycol salicylate) showed a particularly superior edema inhibition rate after 5 hours compared to LOX (1.0% by mass) (Group C: high LOX). Thus, it was shown that LOX (0.5% by mass) + glycol salicylate (5.0% by mass) (Group D: LOX + glycol salicylate) has the effect of sustaining the anti-inflammatory action (maintaining the action of LOX).
(製剤例)
以下の表3~表14に記載した成分を攪拌・混合して溶解後、各製剤例の医薬組成物を得ることができる。
製造方法としては、上記成分及び分量を取り、日本薬局方製剤総則「外用液剤」、「ゲル剤」、「パップ剤」、「テープ剤」の項に準じて製造することができる。
なお、例えば、液状又は半固形状の組成物を具体的な剤形として製剤化する場合においては、剤形に応じて適宜、液状又は半固形状の組成物を容器(例えば、ボトル状容器、チューブ状容器、シート状容器、スプレー剤用容器等)に収容する、液状又は半固形状の組成物を支持体に展延して成形する、噴射剤と混合したうえでエアゾール缶に収容する等、各剤形について公知の手段を適用すればよい。
また、パップとテープの製造を行う場合にも、液状又は半固形状の組成物を支持体に展延して成形する等、公知の手段を適用すればよい。
(Formulation example)
After the ingredients shown in Tables 3 to 14 below are dissolved by stirring and mixing, the pharmaceutical compositions of each formulation example can be obtained.
The preparation can be produced by taking the above-mentioned ingredients and amounts and following the procedures prescribed in the General Provisions for Preparations in the Japanese Pharmacopoeia, sections on "external solutions,""gels,""poultices," and "tapes."
For example, when a liquid or semi-solid composition is formulated as a specific dosage form, a known means may be applied to each dosage form, such as placing the liquid or semi-solid composition in a container (e.g., a bottle-shaped container, a tube-shaped container, a sheet-shaped container, a spray container, etc.) as appropriate for the dosage form, spreading the liquid or semi-solid composition on a support to form a shape, or mixing with a propellant and then placing it in an aerosol can.
In addition, when producing a poultice or tape, a known method may be applied, such as spreading a liquid or semi-solid composition on a support and molding it.
表2~表5において、
※1 ロキソプロフェンナトリウム1g(無水物換算)に相当する
※2 ロキソプロフェンナトリウム2g(無水物換算)に相当する
※3 原生薬として0.1g相当
※4 原生薬として0.44g相当
※5 任意で1種類以上選択し、適量添加する
In Tables 2 to 5,
*1 Equivalent to 1g of loxoprofen sodium (anhydrous equivalent) *2 Equivalent to 2g of loxoprofen sodium (anhydrous equivalent) *3 Equivalent to 0.1g of raw herbal medicine *4 Equivalent to 0.44g of raw herbal medicine *5 One or more types may be selected and added in appropriate amounts
表6~表8において、
※1 ロキソプロフェンナトリウム1g(無水物換算)に相当する
※2 ロキソプロフェンナトリウム2g(無水物換算)に相当する
※3 原生薬として0.1g相当
※4 原生薬として0.44g相当
※5 任意で1種類以上選択し、適量添加する
In Tables 6 to 8,
*1 Equivalent to 1g of loxoprofen sodium (anhydrous equivalent) *2 Equivalent to 2g of loxoprofen sodium (anhydrous equivalent) *3 Equivalent to 0.1g of raw herbal medicine *4 Equivalent to 0.44g of raw herbal medicine *5 One or more types may be selected and added in appropriate amounts
表9~表11において
※1 ロキソプロフェンナトリウム1g(無水物換算)に相当する
※2 ロキソプロフェンナトリウム2g(無水物換算)に相当する
※3 ロキソプロフェンナトリウム0.5g(無水物換算)に相当する
※4 原生薬として0.2g相当
In Tables 9 to 11, *1 is equivalent to 1g of loxoprofen sodium (anhydrous equivalent) *2 is equivalent to 2g of loxoprofen sodium (anhydrous equivalent) *3 is equivalent to 0.5g of loxoprofen sodium (anhydrous equivalent) *4 is equivalent to 0.2g of raw herbal medicine
表12~表14において
※1 ロキソプロフェンナトリウム5g(無水物換算)に相当する
※2 ロキソプロフェンナトリウム7.14g(無水物換算)に相当する
※3 ロキソプロフェンナトリウム8.33g(無水物換算)に相当する
In Tables 12 to 14, *1 is equivalent to 5g of loxoprofen sodium (anhydrous equivalent) *2 is equivalent to 7.14g of loxoprofen sodium (anhydrous equivalent) *3 is equivalent to 8.33g of loxoprofen sodium (anhydrous equivalent)
以上、本発明の好ましい実施形態および実施例を説明したが、本発明はこれらに限定されることはない。本発明の趣旨を逸脱しない範囲で、構成の付加、省略、置換、およびその他の変更が可能である。 The above describes preferred embodiments and examples of the present invention, but the present invention is not limited to these. Additions, omissions, substitutions, and other modifications of the configuration are possible without departing from the spirit of the present invention.
本発明の、ロキソプロフェン又はその塩、およびサリチル酸類を含有する医薬組成物は、抗炎症作用に優れており、極めて有用である。 The pharmaceutical composition of the present invention containing loxoprofen or a salt thereof and a salicylic acid has excellent anti-inflammatory effects and is extremely useful.
Claims (8)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2022161331 | 2022-10-06 | ||
JP2022161331 | 2022-10-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2024055826A true JP2024055826A (en) | 2024-04-18 |
Family
ID=90716491
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023173304A Pending JP2024055826A (en) | 2022-10-06 | 2023-10-05 | Loxoprofen or salt thereof and pharmaceutical composition containing salicylic acid |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP2024055826A (en) |
-
2023
- 2023-10-05 JP JP2023173304A patent/JP2024055826A/en active Pending
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5989095B2 (en) | Transdermal composition of ibuprofen and method of use thereof | |
US20060211688A1 (en) | Vehicle for topical delivery of anti-inflammatory compounds | |
US20060241175A1 (en) | Vehicle for topical delivery of anti-inflammatory compounds | |
WO2017111167A1 (en) | Pharmaceutical preparation containing loxoprofen | |
JP4549006B2 (en) | Gel ointment | |
JP5052558B2 (en) | Gel ointment | |
WO2010103845A1 (en) | External preparation containing analgesic/anti-inflammatory agent | |
WO2010103844A1 (en) | External preparation containing analgesic/anti-inflammatory agent | |
JP6189668B2 (en) | Loxoprofen-containing external coating | |
JP2009013171A (en) | Memantine-containing transdermally absorbable preparation | |
JPWO2010103843A1 (en) | Topical analgesic / anti-inflammatory agent | |
JP6344947B2 (en) | Loxoprofen-containing solid preparation for external use | |
JP2017226705A (en) | Loxoprofen-containing external solid agent | |
JP2019081755A (en) | Composition | |
JP2019142856A (en) | Loxoprofen-containing skin external preparation | |
WO2023277075A1 (en) | Topical skin agent containing heparinoid and loxoprofen or salt thereof | |
JP2024055826A (en) | Loxoprofen or salt thereof and pharmaceutical composition containing salicylic acid | |
WO2018124281A1 (en) | Topical composition | |
JP5091472B2 (en) | Adhesives and patches | |
JP6503627B2 (en) | Pharmaceutical liquid composition | |
JP2024091588A (en) | A skin preparation containing a heparinoid and at least one member selected from the group consisting of loxoprofen, its salts and their hydrates. | |
JP2024035209A (en) | pharmaceutical composition | |
JP2024091587A (en) | Skin preparations containing heparinoids | |
WO2024135819A1 (en) | Skin external preparation containing heparinoid and at least one selected from group consisting of loxoprofen, salt thereof and hydrates of same | |
JP2010006761A (en) | Percutaneous absorption patch containing fentanyl or its salt and method for producing the same |