JP2021105056A - External composition - Google Patents
External composition Download PDFInfo
- Publication number
- JP2021105056A JP2021105056A JP2021069617A JP2021069617A JP2021105056A JP 2021105056 A JP2021105056 A JP 2021105056A JP 2021069617 A JP2021069617 A JP 2021069617A JP 2021069617 A JP2021069617 A JP 2021069617A JP 2021105056 A JP2021105056 A JP 2021105056A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- external composition
- minoxidil
- salt
- composition according
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 103
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 31
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000011975 tartaric acid Substances 0.000 claims abstract description 28
- 235000002906 tartaric acid Nutrition 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 239000002253 acid Substances 0.000 claims abstract description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 62
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 claims description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 27
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 24
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 22
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 21
- 229940058015 1,3-butylene glycol Drugs 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
- 235000019437 butane-1,3-diol Nutrition 0.000 claims description 17
- 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 claims description 16
- 150000005846 sugar alcohols Polymers 0.000 claims description 12
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 10
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 8
- 239000000174 gluconic acid Substances 0.000 claims description 8
- 235000012208 gluconic acid Nutrition 0.000 claims description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 6
- 239000011976 maleic acid Substances 0.000 claims description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 5
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 5
- 239000004327 boric acid Substances 0.000 claims description 5
- 229910017604 nitric acid Inorganic materials 0.000 claims description 5
- 235000011187 glycerol Nutrition 0.000 claims description 4
- 230000000699 topical effect Effects 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 2
- 235000013772 propylene glycol Nutrition 0.000 claims description 2
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 abstract description 59
- 229960003632 minoxidil Drugs 0.000 abstract description 59
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract description 34
- 238000001556 precipitation Methods 0.000 abstract description 25
- 239000013078 crystal Substances 0.000 abstract description 11
- 238000009472 formulation Methods 0.000 abstract description 4
- 239000002244 precipitate Substances 0.000 abstract 2
- 239000008213 purified water Substances 0.000 description 16
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 12
- 230000000052 comparative effect Effects 0.000 description 10
- 229940095064 tartrate Drugs 0.000 description 9
- 239000004310 lactic acid Substances 0.000 description 7
- 235000014655 lactic acid Nutrition 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- -1 diacetone alcohols Chemical class 0.000 description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 5
- 239000004094 surface-active agent Substances 0.000 description 5
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 4
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-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
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 0.000 description 4
- GOQYKNQRPGWPLP-UHFFFAOYSA-N heptadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 150000004665 fatty acids Chemical class 0.000 description 3
- 210000004209 hair Anatomy 0.000 description 3
- 230000003779 hair growth Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- MRAMPOPITCOOIN-VIFPVBQESA-N (2r)-n-(3-ethoxypropyl)-2,4-dihydroxy-3,3-dimethylbutanamide Chemical compound CCOCCCNC(=O)[C@H](O)C(C)(C)CO MRAMPOPITCOOIN-VIFPVBQESA-N 0.000 description 2
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CAYHVMBQBLYQMT-UHFFFAOYSA-N 2-decyltetradecan-1-ol Chemical compound CCCCCCCCCCCCC(CO)CCCCCCCCCC CAYHVMBQBLYQMT-UHFFFAOYSA-N 0.000 description 2
- LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 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 2
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- MBMBGCFOFBJSGT-KUBAVDMBSA-N all-cis-docosa-4,7,10,13,16,19-hexaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- BTFJIXJJCSYFAL-UHFFFAOYSA-N arachidyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCO BTFJIXJJCSYFAL-UHFFFAOYSA-N 0.000 description 2
- KVYGGMBOZFWZBQ-UHFFFAOYSA-N benzyl nicotinate Chemical compound C=1C=CN=CC=1C(=O)OCC1=CC=CC=C1 KVYGGMBOZFWZBQ-UHFFFAOYSA-N 0.000 description 2
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- RZMKWKZIJJNSLQ-UHFFFAOYSA-M carpronium chloride Chemical compound [Cl-].COC(=O)CCC[N+](C)(C)C RZMKWKZIJJNSLQ-UHFFFAOYSA-M 0.000 description 2
- 229950003631 carpronium chloride Drugs 0.000 description 2
- 229940082500 cetostearyl alcohol Drugs 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- SWXVUIWOUIDPGS-UHFFFAOYSA-N diacetone alcohol Chemical compound CC(=O)CC(C)(C)O SWXVUIWOUIDPGS-UHFFFAOYSA-N 0.000 description 2
- 229960000525 diphenhydramine hydrochloride Drugs 0.000 description 2
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 2
- 229960000735 docosanol Drugs 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229960003720 enoxolone Drugs 0.000 description 2
- FIPPFBHCBUDBRR-UHFFFAOYSA-N henicosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCO FIPPFBHCBUDBRR-UHFFFAOYSA-N 0.000 description 2
- SFFVATKALSIZGN-UHFFFAOYSA-N hexadecan-7-ol Chemical class CCCCCCCCCC(O)CCCCCC SFFVATKALSIZGN-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
- 229940055577 oleyl alcohol Drugs 0.000 description 2
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 2
- 229940101267 panthenol Drugs 0.000 description 2
- 235000020957 pantothenol Nutrition 0.000 description 2
- 239000011619 pantothenol Substances 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- ZUFQODAHGAHPFQ-UHFFFAOYSA-N pyridoxine hydrochloride Chemical compound Cl.CC1=NC=C(CO)C(CO)=C1O ZUFQODAHGAHPFQ-UHFFFAOYSA-N 0.000 description 2
- 235000019171 pyridoxine hydrochloride Nutrition 0.000 description 2
- 239000011764 pyridoxine hydrochloride Substances 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 2
- 229940098465 tincture Drugs 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 229940042585 tocopherol acetate Drugs 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- OYHQOLUKZRVURQ-NTGFUMLPSA-N (9Z,12Z)-9,10,12,13-tetratritiooctadeca-9,12-dienoic acid Chemical compound C(CCCCCCC\C(=C(/C\C(=C(/CCCCC)\[3H])\[3H])\[3H])\[3H])(=O)O OYHQOLUKZRVURQ-NTGFUMLPSA-N 0.000 description 1
- 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 1
- 150000000211 1-dodecanols Chemical class 0.000 description 1
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- 150000000218 1-tetradecanols Chemical class 0.000 description 1
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- JYZLSYFPFQTNNO-UHFFFAOYSA-N 2-octyldecan-1-ol Chemical compound CCCCCCCCC(CO)CCCCCCCC JYZLSYFPFQTNNO-UHFFFAOYSA-N 0.000 description 1
- ZIMGGGWCDYVHOY-UHFFFAOYSA-N 3-hydroxy-2-imino-6-(1-piperidinyl)-4-pyrimidinamine Chemical compound N=C1N(O)C(N)=CC(N2CCCCC2)=N1 ZIMGGGWCDYVHOY-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
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 235000021357 Behenic acid Nutrition 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 235000015655 Crocus sativus Nutrition 0.000 description 1
- 244000124209 Crocus sativus Species 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 235000008694 Humulus lupulus Nutrition 0.000 description 1
- 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 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 241000408747 Lepomis gibbosus Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- NWBJYWHLCVSVIJ-UHFFFAOYSA-N N-benzyladenine Chemical compound N=1C=NC=2NC=NC=2C=1NCC1=CC=CC=C1 NWBJYWHLCVSVIJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 244000178231 Rosmarinus officinalis Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
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Abstract
Description
本発明は、ミノキシジルを有効成分とする外用組成物に関する。更に詳細には、結晶析出を抑制した、ミノキシジルの溶解性に優れたミノキシジル含有外用組成物に関する。 The present invention relates to an external composition containing minoxidil as an active ingredient. More specifically, the present invention relates to a minoxidil-containing external composition having excellent solubility of minoxidil, which suppresses crystal precipitation.
ミノキシジルは化学名を6−(1−ピペリジニル)−2,4−ピリミジンジアミン−3−オキサイドと称し、育毛剤としての適応が知られており(特許文献1)、優れた育毛・発毛効果を発揮する薬剤として多数の報告がある。 Minoxidil has a chemical name of 6- (1-piperidinyl) -2,4-pyrimidinediamine-3-oxide and is known to be applied as a hair restorer (Patent Document 1), and has excellent hair growth and hair growth effects. There are many reports as a drug to exert.
ミノキシジルを配合した育毛剤に求められる基本的な性能は、頭皮からのミノキシジルの吸収性に優れることである(特許文献2)。頭皮からのミノキシジルの吸収性を確保するためには、製剤中のミノキシジルが溶解状態で存在することが好ましく、製剤中で結晶析出等が生じないことが求められる。ミノキシジルは水やほとんどの油に対して溶解性が悪く、ミノキシジルの溶解性を確保するため、多価アルコールの配合や酸による溶解性確保が広く知られている(特許文献3〜5)。 The basic performance required for a hair restorer containing minoxidil is that it has excellent absorption of minoxidil from the scalp (Patent Document 2). In order to ensure the absorption of minoxidil from the scalp, it is preferable that minoxidil in the preparation exists in a dissolved state, and it is required that crystal precipitation or the like does not occur in the preparation. Minoxidil has poor solubility in water and most oils, and in order to secure the solubility of minoxidil, it is widely known to blend a polyhydric alcohol and to secure the solubility with an acid (Patent Documents 3 to 5).
多価アルコールは、種類によっては過剰に配合するとべたつき等使用感の悪化へのつながりが懸念されるため、過剰に配合しないことが望ましい。特許文献6には、プロピレングリコールは粘性と粘着性が高いので、組成物中に30〜50%の大量のプロピレングリコールや類似の成分が含まれることは医薬品としてまたは化粧品として好ましくないことが示されている。 Depending on the type of polyhydric alcohol, it is desirable not to add it excessively because there is a concern that excessive addition may lead to deterioration of usability such as stickiness. Patent Document 6 shows that propylene glycol is highly viscous and sticky, and therefore, it is not preferable as a pharmaceutical product or a cosmetic product to contain a large amount of propylene glycol or a similar component of 30 to 50% in the composition. ing.
また、酸に関しては、特許文献6において、好ましい酸としてカルボン酸の一種である酢酸や乳酸が記載されている。カルボン酸の一種である酒石酸は、水にも低級アルコールにも溶けやすく、製剤調製に有用な酸である。 Regarding the acid, Patent Document 6 describes acetic acid and lactic acid, which are a kind of carboxylic acid, as preferable acids. Tartaric acid, which is a kind of carboxylic acid, is easily dissolved in water and lower alcohols, and is a useful acid for preparation of pharmaceutical products.
本発明者らは、酸として有用な酒石酸を選択し、ミノキシジルの溶解性を確保するべく外用組成物の製造を試みたところ、意外にも、結晶析出が生じ、ミノキシジルの溶解性確保にも至らないことが判明した。 The present inventors selected tartrate acid, which is useful as an acid, and attempted to produce a composition for external use in order to secure the solubility of minoxidil. Surprisingly, crystal precipitation occurred, and the solubility of minoxidil was also ensured. It turned out not.
したがって、本発明は、酒石酸を含有したミノキシジル含有外用組成物において、ミノキシジルの溶解性を確保し、かつ結晶析出を抑制したミノキシジル含有外用組成物を提供することを課題とする。 Therefore, it is an object of the present invention to provide a minoxidil-containing topical composition containing tartaric acid, which ensures the solubility of minoxidil and suppresses crystal precipitation.
本発明者らは、上記課題を解決すべく鋭意検討を重ねた結果、酒石酸及び/又はその塩、水を含むミノキシジル含有外用組成物を製造する場合は、さらに特定の酸及び/又はその塩を配合し、かつ、水に対する酒石酸及び/又はその塩の配合比率を特定範囲とすることにより、ミノキシジルの溶解性を確保し、かつ結晶析出を抑制したミノキシジル含有外用組成物と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 diligent studies to solve the above problems, the present inventors have further added a specific acid and / or a salt thereof when producing a minoxidil-containing external composition containing tartrate acid and / or a salt thereof and water. We have found that by blending and setting the blending ratio of tartrate acid and / or a salt thereof to water within a specific range, it is possible to obtain a minoxidil-containing external composition that secures the solubility of minoxidil and suppresses crystal precipitation. Has been completed.
すなわち本発明は、
(1)(a)ミノキシジル、(b)酒石酸及び/又はその塩、(c)リン酸、クエン酸、乳酸、塩酸、グルコン酸、酢酸、硫酸、ホウ酸、硝酸、及びマレイン酸からなる群から選ばれる少なくとも1種の酸及び/又はこれらの塩、及び(d)水を含有し、かつ(b)の含有量が(d)1質量部に対し0.025質量部未満であることを特徴とする外用組成物、
(2)(c)成分が、リン酸、クエン酸、乳酸、塩酸、グルコン酸、及び酢酸からなる群から選ばれる少なくとも1種の酸及び/又はこれらの塩である、(1)に記載の外用組成物、
(3)(a)の含有量が5w/v%以上である、(1)に記載の外用組成物、
(4)更に、多価アルコールを含有する(1)〜(3)に記載の外用組成物、
(5)多価アルコールが、1,3−ブチレングリコール、プロピレングリコール、及びグリセリンからなる群から選ばれる少なくとも1つである、(4)に記載の外用組成物、
(6)多価アルコールの含有量が2〜50w/v%である、(4)または(5)に記載の外用組成物、
(7)更に、低級アルコールを含有する(1)〜(6)のいずれかに記載の外用組成物、
(8)低級アルコールの含有量が50w/v%以上である(7)に記載の外用組成物、
(9)(d)の含有量が5〜30w/v%である、(1)に記載の外用組成物、
(10)pHが5.0〜7.0である、(1)〜(9)のいずれかに記載の外用組成物、
である。
That is, the present invention
From the group consisting of (1) (a) minoxidyl, (b) tartaric acid and / or a salt thereof, (c) phosphoric acid, citric acid, lactic acid, hydrochloric acid, gluconic acid, acetic acid, sulfuric acid, boric acid, nitric acid, and maleic acid. It is characterized by containing at least one selected acid and / or a salt thereof, and (d) water, and the content of (b) is less than 0.025 parts by mass with respect to (d) 1 part by mass. External composition,
(2) The component (c) is at least one acid and / or a salt thereof selected from the group consisting of phosphoric acid, citric acid, lactic acid, hydrochloric acid, gluconic acid, and acetic acid, according to (1). External composition,
(3) The external composition according to (1), wherein the content of (a) is 5 w / v% or more.
(4) The external composition according to (1) to (3), which further contains a polyhydric alcohol.
(5) The external composition according to (4), wherein the polyhydric alcohol is at least one selected from the group consisting of 1,3-butylene glycol, propylene glycol, and glycerin.
(6) The external composition according to (4) or (5), wherein the content of the polyhydric alcohol is 2 to 50 w / v%.
(7) The external composition according to any one of (1) to (6), which further contains a lower alcohol.
(8) The external composition according to (7), wherein the content of the lower alcohol is 50 w / v% or more.
(9) The external composition according to (1), wherein the content of (d) is 5 to 30 w / v%.
(10) The external composition according to any one of (1) to (9), which has a pH of 5.0 to 7.0.
Is.
本発明により、酒石酸及び/又はその塩と水を含有したミノキシジル含有外用組成物において、ミノキシジルの溶解性を確保し、かつ結晶析出を抑制したミノキシジル含有外用組成物を提供することが可能になった。 INDUSTRIAL APPLICABILITY According to the present invention, it has become possible to provide a minoxidil-containing topical composition containing tartrate acid and / or a salt thereof and water, which ensures the solubility of minoxidil and suppresses crystal precipitation. ..
本発明によれば、ミノキシジルと酒石酸及び/又はその塩と水を含有し、さらにリン酸、クエン酸、乳酸、塩酸、グルコン酸、酢酸、硫酸、ホウ酸、硝酸、及びマレイン酸から選ばれる少なくとも1種の酸及び/又はこれらの塩を含有し、水に対する酒石酸及び/又はその塩の含有量を特定範囲とした外用組成物は、ミノキシジルの溶解性を確保でき、かつ結晶析出を抑制したミノキシジル含有外用組成物となる。
本発明の外用組成物において用いるミノキシジルは、通常医薬品に用いられる品質のものを適宜使用することができる。また、本発明における外用組成物において、ミノキシジルの含有量が多くなるにつれ溶解性の課題が大きくなるため、外用組成物中におけるミノキシルの濃度が高いほど、本発明を実施する意義が大きい。具体的には、本発明の外用組成物中1w/v%以上が好ましく、より好ましくは3w/v%以上であり、更に好ましくは5w/v%以上である。
According to the present invention, at least selected from phosphoric acid, citric acid, lactic acid, hydrochloric acid, gluconic acid, acetic acid, sulfuric acid, boric acid, nitric acid, and maleic acid, which contains minoxidyl and tartrate acid and / or a salt thereof and water. An external composition containing one kind of acid and / or a salt thereof and having a specific range of tartrate acid and / or a salt thereof in water can secure the solubility of minoxidil and suppress crystal precipitation. It is a composition for external use.
As the minoxidil used in the external composition of the present invention, those of the quality usually used for pharmaceutical products can be appropriately used. Further, in the external composition of the present invention, the problem of solubility increases as the content of minoxidil increases. Therefore, the higher the concentration of minoxidil in the external composition, the greater the significance of carrying out the present invention. Specifically, it is preferably 1 w / v% or more, more preferably 3 w / v% or more, and further preferably 5 w / v% or more in the external composition of the present invention.
本発明の外用組成物では、酒石酸及び/又はその塩の含有量は、0.01〜0.25w/v%未満が好ましく、より好ましくは0.01〜0.2w/v%未満である。また、本発明の外用組成物においては、酒石酸及び/又はその塩の含有量は、水1質量部に対し0.001質量部以上が好ましく、上限は0.025質量部未満である。0.025質量部以上配合すると外用組成物中に結晶析出が生じるからである。 In the external composition of the present invention, the content of tartaric acid and / or a salt thereof is preferably less than 0.01 to 0.25 w / v%, more preferably less than 0.01 to 0.2 w / v%. Further, in the external composition of the present invention, the content of tartaric acid and / or a salt thereof is preferably 0.001 part by mass or more with respect to 1 part by mass of water, and the upper limit is less than 0.025 part by mass. This is because when 0.025 parts by mass or more is blended, crystal precipitation occurs in the external composition.
本発明の外用組成物において酒石酸及び/又はその塩と組み合わせる酸及び/又はその塩としては、リン酸、クエン酸、乳酸、塩酸、グルコン酸、酢酸、硫酸、ホウ酸、硝酸、マレイン酸、及び/又はこれらの塩が挙げられる。このうち、析出が生じない澄明な製剤が得られる点から、より好ましいのはリン酸、クエン酸、乳酸、塩酸、グルコン酸、酢酸、及び/又はこれらの塩である。これら酒石酸及び/又はその塩と組み合わせる酸及び/又はその塩は、1種又は2種以上更に組み合わせてもよい。
また、本発明の外用組成物は、主薬成分のミノキシジルの安定性、使用時の肌への刺激感、薬物の浸透性、使用感等の点から、そのpHを4.0〜8.0の範囲に調整することが好ましく、5.0〜7.0の範囲が更に好ましい。
The acid and / or salt thereof to be combined with tartrate acid and / or a salt thereof in the external composition of the present invention includes phosphoric acid, citric acid, lactic acid, hydrochloric acid, gluconic acid, acetic acid, sulfuric acid, boric acid, nitric acid, maleic acid, and maleic acid. / Or these salts. Of these, phosphoric acid, citric acid, lactic acid, hydrochloric acid, gluconic acid, acetic acid, and / or salts thereof are more preferable from the viewpoint of obtaining a clear preparation that does not cause precipitation. The acid and / or a salt thereof to be combined with these tartaric acid and / or a salt thereof may be further combined in one kind or two or more kinds.
In addition, the external composition of the present invention has a pH of 4.0 to 8.0 in terms of the stability of minoxidil, which is the main ingredient, irritation to the skin during use, the permeability of the drug, and the feeling of use. It is preferable to adjust to a range, and a range of 5.0 to 7.0 is more preferable.
また、本発明の外用組成物中に配合できる水の含有量としては、2〜75w/v%が好ましく、より好ましくは5〜50w/v%であり、更に好ましくは5〜30w/v%である。 The content of water that can be blended in the external composition of the present invention is preferably 2 to 75 w / v%, more preferably 5 to 50 w / v%, still more preferably 5 to 30 w / v%. be.
本発明の外用組成物は、更に必要により多価アルコールを配合することができる。多価アルコールの例としては、1,3−ブチレングリコール、ジプロピレングリコール、プロピレングリコール、グリセリン等が挙げられ、これらを1種又は2種以上組み合わせてもよい。多価アルコールの含有量は、全組成物中好ましくは2〜50w/v%であり、より好ましくは5〜30w/v%未満であり、更に好ましくは5〜20w/v%である。本発明において多価アルコールを30w/v%以上配合しなくても、ミノキシジルの溶解性を確保できる。 The external composition of the present invention may further contain a polyhydric alcohol, if necessary. Examples of the polyhydric alcohol include 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin and the like, and these may be used alone or in combination of two or more. The content of the polyhydric alcohol is preferably 2 to 50 w / v%, more preferably less than 5 to 30 w / v%, and even more preferably 5 to 20 w / v% in the total composition. In the present invention, the solubility of minoxidil can be ensured without blending 30 w / v% or more of the polyhydric alcohol.
本発明の外用組成物において用いる低級アルコールとしては、炭素数1〜5のものが好ましく、例えばエタノールやイソプロパノールなどが好ましく、これらを組み合わせて使用しても良い。本発明の外用組成物中の低級アルコールの含有量は、全組成物中20w/v%以上が好ましく、より好ましくは35w/v%以上であり、更に好ましくは50w/v%以上である。上限は80w/v%が好ましい。 As the lower alcohol used in the external composition of the present invention, those having 1 to 5 carbon atoms are preferable, for example, ethanol and isopropanol are preferable, and these may be used in combination. The content of the lower alcohol in the external composition of the present invention is preferably 20 w / v% or more, more preferably 35 w / v% or more, still more preferably 50 w / v% or more in the total composition. The upper limit is preferably 80 w / v%.
本発明の外用組成物は、更に必要により高級アルコールを配合することができる。高級アルコールの例としては、炭素数が6〜24のジアセトンアルコール、カプロイルアルコール、カプリリルアルコール、カプリルアルコール、ラウリルアルコール、トリデカノール、ミリスチルアルコール、ペンタデカノール、セチルアルコール、ヘキシルデカノール、イソセチルアルコール、セトステアリルアルコール、ヘプタデカノール、ステアリルアルコール、オレイルアルコール、イソステアリルアルコール、オクチルデカノール、ノナデカノール、アラキルアルコール、オクチルドデカノール、ヘンイコサノール、ベヘニルアルコール、デシルテトラデカノールがより好ましく、そのうち、ジアセトンアルコール、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、ヘキシルデカノール、セトステアリルアルコール、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、アラキルアルコール、オクチルドデカノール、ベヘニルアルコール、デシルテトラデカノールがさらに好ましい。本発明の高級アルコールは、1種又は2種以上組み合わせて使用しても良い。高級アルコールの含有量は、本発明の効果の点から外用組成物中0.05〜2w/v%が好ましく、0.1〜1.5w/v%がより好ましく、更に好ましくは0.25〜1.5w/v%である。 The external composition of the present invention may further contain a higher alcohol, if necessary. Examples of higher alcohols include diacetone alcohols with 6 to 24 carbon atoms, caproyl alcohols, caprylyl alcohols, capryl alcohols, lauryl alcohols, tridecanols, myristyl alcohols, pentadecanols, cetyl alcohols, hexyldecanols, isocetyl alcohols, More preferred are cetostearyl alcohol, heptadecanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, octyldecanol, nonadecanol, araquil alcohol, octyldodecanol, henicosanol, behenyl alcohol, decyltetradecanol, of which diacetone alcohol, Lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyldecanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, araquil alcohol, octyldodecanol, behenyl alcohol and decyltetradecanol are more preferable. The higher alcohol of the present invention may be used alone or in combination of two or more. The content of the higher alcohol is preferably 0.05 to 2 w / v%, more preferably 0.1 to 1.5 w / v%, still more preferably 0.25 to 0.25% in the external composition from the viewpoint of the effect of the present invention. It is 1.5 w / v%.
本発明の外用組成物は、更に必要により高級脂肪酸を配合することができる。高級脂肪酸の例としては、炭素数10〜22のものが好ましく、例えばイソステアリン酸、オレイン酸、ステアリン酸、カプリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、パルミトレイン酸、リノール酸、リノレン酸、エライジン酸、アラキジン酸、アラキドン酸、ベヘン酸、エイコサペンタエン酸、ドコサヘキサエン酸等が挙げられ、これらを1種又は2種以上組み合わせてもよい。このうち、炭素数18のものが好ましく、特にイソステアリン酸又はオレイン酸が好ましい。高級脂肪酸の含有量は、全組成物中好ましくは0.1〜10w/v%であり、より好ましくは1〜6w/v%である。 The external composition of the present invention may further contain a higher fatty acid, if necessary. Examples of higher fatty acids are preferably those having 10 to 22 carbon atoms, for example, isostearic acid, oleic acid, stearic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitreic acid, linoleic acid, linolenic acid, and elaidic acid. , Arachidic acid, arachidonic acid, behenic acid, elaidic acid, docosahexaenoic acid and the like, and these may be used alone or in combination of two or more. Of these, those having 18 carbon atoms are preferable, and isostearic acid or oleic acid is particularly preferable. The content of the higher fatty acid is preferably 0.1 to 10 w / v%, more preferably 1 to 6 w / v% in the total composition.
本発明の外用組成物は、更に必要により界面活性剤を配合することができる。しかしながら、界面活性剤の添加は、使用感やミノキシジルの皮膚吸収に影響を与える可能性があり、本発明の外用組成物では、界面活性剤を配合しなくてもミノキシジルの溶解性を確保できるため、実質的に界面活性剤を含まないものとすることが好ましい。 The external composition of the present invention may further contain a surfactant, if necessary. However, the addition of a surfactant may affect the feeling of use and the skin absorption of minoxidil, and the external composition of the present invention can ensure the solubility of minoxidil without adding a surfactant. , It is preferable that the surfactant is substantially free of the surfactant.
本発明の外用組成物は、上記した各成分の他に、本発明の効果を損なわない範囲で、必要な活性成分や補助成分を加えることができる。本発明の外用組成物に添加、配合することが好ましい薬効成分としては、メントール、ビタミンEアセテート、パントテニルエチルエーテル、ヒノキチオール、塩酸ピリドキシン、グリチルレチン酸、塩酸ジフェンヒドラミン、パンテノールから成る群より選ばれた成分が挙げられる。 In the external composition of the present invention, in addition to the above-mentioned components, necessary active ingredients and auxiliary ingredients can be added as long as the effects of the present invention are not impaired. Preferable medicinal ingredients to be added to and blended with the external composition of the present invention were selected from the group consisting of menthol, vitamin E acetate, pantothenyl ethyl ether, hinokitiol, pyridoxine hydrochloride, glycyrrhetinic acid, diphenhydramine hydrochloride and panthenol. Ingredients are mentioned.
これら選択成分の添加量は、特に制約はなく、使用感やミノキシジルの安定性あるいは溶剤系組成等を考慮しながら実験的に定めることができる。 The amount of these selected components added is not particularly limited, and can be experimentally determined in consideration of usability, stability of minoxidil, solvent-based composition, and the like.
本発明の外用組成物においては、上記した成分の他、本発明の効果を損なわない範囲で、一般の外用剤に用いられる種々の活性成分や補助成分を配合することができる。例えば、賦形剤、育毛成分(6−ベンジルアミノプリン、アデノシン、ペンタデカン酸グリセリド、何首鳥等)、血管拡張剤(塩化カルプロニウム、ニコチン酸ベンジル、センブリ抽出液、オタネニンジンエキス、チクセツニンジンチンキ、トウガラシチンキ等)、抗ヒスタミン剤(塩酸イソチペンジル等)、抗炎症剤(グアイアズレン等)、角質溶解剤(尿素、サリチル酸等)、殺菌剤(グルコン酸クロルヘキシジン、イソプロピルメチルフェノール、第4級アンモニウム塩、ピロクトンオラミン等)、保湿剤(ヒアルロン酸又はその塩、コンドロイチン硫酸等)、各種動植物(イチイ、ボタンピ、カンゾウ、オトギリソウ、附子、ビワ、カワラヨモギ、コンフリー、アシタバ、サフラン、サンシシ、ローズマリー、セージ、モッコウ、セイモッコウ、ホップ、プラセンタ、ノコギリヤシ、パンプキンシード等)の抽出物、ビタミン類(酢酸レチノール、アスコルビン酸、硝酸チアミン、シアノコバラミン、ビオチン等)、抗酸化剤(ジブチルヒドロキシトルエン、ピロ亜硫酸ナトリウム、トコフェロール、エデト酸ナトリウム、アスコルビン酸、イソプロピルガレート等)、溶解補助剤(アジピン酸ジイソプロピル、ミリスチン酸イソプロピル、各種植物油、各種動物油、アルキルグリセリルエーテル、炭化水素類等)、代謝賦活剤、ゲル化剤(水溶性高分子等)、粘着剤、香料、清涼化剤(ハッカ油、カンフル等)、染料等の通常使用される成分を配合することができる。 In the external composition of the present invention, in addition to the above-mentioned components, various active ingredients and auxiliary components used in general external preparations can be blended as long as the effects of the present invention are not impaired. For example, excipients, hair growth ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, tocopherols, etc.), vasodilators (carpronium chloride, benzyl nicotinate, assembly extract, otane carrot extract, chixetsu carrot tincture, etc. Togarashi tincture, etc.), antihistamine (isotipendyl hydrochloride, etc.), anti-inflammatory agent (guaizulene, etc.), keratolytic agent (urea, salicylic acid, etc.), bactericide (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salt, pyroctonora Min, etc.), moisturizer (hyaluronic acid or its salt, chondroitin sulfate, etc.), various animals and plants (ichii, buttonpi, kanzo, otogirisou, tsuko, biwa, kawarayomogi, comfrey, ascorbic acid, saffron, sanshishi, rosemary, sage, mokko , Seimokko, hops, placenta, sawtooth palm, pumpkin seed, etc.), vitamins (retinol acetate, ascorbic acid, thiamine nitrate, cyanocobalamine, biotin, etc.), antioxidants (dibutylhydroxytoluene, sodium pyrosulfate, tocopherol, edet) Sodium acid, ascorbic acid, isopropyl gallate, etc.), solubilizers (diisopropyl adipate, isopropyl myristate, various vegetable oils, various animal oils, alkylglyceryl ethers, hydrocarbons, etc.), metabolic activators, gelling agents (highly water-soluble) It can contain commonly used ingredients such as molecules), adhesives, fragrances, cooling agents (such as peppermint oil and camphor), and dyes.
本発明の外用組成物は、ローション剤、エアゾール剤、トニック剤、クリーム剤、軟膏剤、ゲル剤等の適当な外用組成物とすることができるが、このうち好ましいのはローション剤である。 The external composition of the present invention can be an appropriate external composition such as a lotion, an aerosol, a tonic, a cream, an ointment, a gel, etc. Among them, a lotion is preferable.
本発明の外用組成物の調製は、常法に従い、上記各成分を含有することにより調製される。 The external composition of the present invention is prepared by containing each of the above components according to a conventional method.
かくして得られる本発明の外用組成物は、頭髪用剤、睫毛用剤、眉毛用剤等の皮膚適用製剤等として使用することができる。 The external composition of the present invention thus obtained can be used as a skin-applied preparation such as a hair agent, an eyelash agent, and an eyebrow agent.
以下に、実施例、比較例及び試験例を記載し、本発明をさらに具体的に説明するが、本発明はこれら実施例等により何ら制約されるものではない。 Hereinafter, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples, but the present invention is not limited to these Examples and the like.
(実施例1)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、リン酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 1)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, an appropriate amount of phosphoric acid, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例2)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、クエン酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 2)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, citric acid appropriate amount, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例3)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、乳酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 3)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, an appropriate amount of lactic acid, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例4)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、塩酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 4)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, hydrochloric acid appropriate amount, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例5)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、グルコン酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 5)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, an appropriate amount of gluconic acid, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例6)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、酢酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 6)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, acetic acid appropriate amount, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例7)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、硫酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 7)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, sulfuric acid appropriate amount, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例8)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、ホウ酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 8)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, boric acid appropriate amount, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例9)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、硝酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 9)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, an appropriate amount of nitric acid, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例10)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、マレイン酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 10)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, maleic acid appropriate amount, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例11)
ミノキシジル5g、プロピレングリコール10g、精製水10g、酒石酸0.2g、リン酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 11)
Minoxidil 5 g, propylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, an appropriate amount of phosphoric acid, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(実施例12)
ミノキシジル5g、グリセリン10g、精製水10g、酒石酸0.2g、リン酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Example 12)
Minoxidil 5 g, glycerin 10 g, purified water 10 g, tartaric acid 0.2 g, an appropriate amount of phosphoric acid, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(比較例1)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、エタノールで全量を100mLとし、撹拌して外用組成物を得た。
(Comparative Example 1)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, and ethanol were added to make a total volume of 100 mL, and the mixture was stirred to obtain an external composition.
(比較例2)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.25g、エタノールで全量を100mLとし、撹拌して外用組成物を得た。
(Comparative Example 2)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.25 g, and ethanol were added to make a total volume of 100 mL, and the mixture was stirred to obtain an external composition.
(比較例3)
ミノキシジル5g、1,3−ブチレングリコール10g、精製水10g、酒石酸0.2g、dl-リンゴ酸適量、エタノールで全量を100mLとし、撹拌してpH6.3の外用組成物を得た。
(Comparative Example 3)
Minoxidil 5 g, 1,3-butylene glycol 10 g, purified water 10 g, tartaric acid 0.2 g, dl-malic acid appropriate amount, and ethanol were added to make the total volume 100 mL, and the mixture was stirred to obtain an external composition having a pH of 6.3.
(処方例)
ミノキシジル5g、1,3−ブチレングリコール5g、プロピレングリコール5g、セチルアルコール0.1g、精製水10g、酒石酸0.2g、l-メントール0.3g、塩酸ピリドキシン0.05g、ビタミンEアセテート0.08g、パントテニルエチルエーテル1g、パンテノール1g、塩化カルプロニウム2g、グリチルレチン酸0.1g、塩酸ジフェンヒドラミン0.1g、ヒノキチオール0.05g、サリチル酸0.2g、抗酸化剤適量、リン酸適量、エタノールで全量を100mLとし、撹拌溶解してpH5.9の外用組成物を得た。
(Prescription example)
Minoxidil 5g, 1,3-butylene glycol 5g, propylene glycol 5g, cetyl alcohol 0.1g, purified water 10g, tartrate acid 0.2g, l-menthol 0.3g, pyridoxin hydrochloride 0.05g, vitamin E acetate 0.08g, Pantothenyl ethyl ether 1 g, panthenol 1 g, carpronium chloride 2 g, glycyrrhetinic acid 0.1 g, diphenhydramine hydrochloride 0.1 g, hinokithiol 0.05 g, salicylic acid 0.2 g, antioxidant appropriate amount, phosphoric acid appropriate amount, ethanol total 100 mL The mixture was stirred and dissolved to obtain an external composition having a pH of 5.9.
比較例1、2の処方を表1、実施例1〜10及び比較例3を表2、実施例11、12を表3に示す。なお、表中の単位はgである。 The formulations of Comparative Examples 1 and 2 are shown in Table 1, Examples 1 to 10 and Comparative Example 3 are shown in Table 2, and Examples 11 and 12 are shown in Table 3. The unit in the table is g.
<試験例1:析出の有無>
比較例1、2に関し、調製段階で生じたミノキシジル以外の析出が、調製直後に認められなかったものを○、析出が認められたものを×とした。結果を表4に示す。
<Test Example 1: Presence or absence of precipitation>
Regarding Comparative Examples 1 and 2, those in which precipitation other than minoxidil generated in the preparation stage was not observed immediately after preparation were evaluated as ◯, and those in which precipitation was observed were evaluated as x. The results are shown in Table 4.
<試験例2:ミノキシジルの溶解>
比較例1〜3、実施例1〜12に関し、調製直後にミノキシジルが完全に溶解したものを○、溶解しなかったものを×とした。結果を表4〜6に示す。
<Test Example 2: Dissolution of minoxidil>
Regarding Comparative Examples 1 to 3 and Examples 1 to 12, those in which minoxidil was completely dissolved immediately after preparation were marked with ◯, and those in which minoxidil was not dissolved were marked with x. The results are shown in Tables 4-6.
<試験例3:析出の有無>
実施例1〜12及び比較例3の外用組成物に関し、調製段階で生じたミノキシジル以外の析出を調製直後に目視で確認し、析出が認められなかったものを◎、極わずかに析出が認められたが問題ないものを○、析出が全体的に認められて白濁し問題であるものを×とした。結果を表5、6に示す。
<Test Example 3: Presence or absence of precipitation>
Regarding the external compositions of Examples 1 to 12 and Comparative Example 3, precipitation other than minoxidil generated in the preparation stage was visually confirmed immediately after preparation, and those in which no precipitation was observed were ⊚, and very slight precipitation was observed. However, those with no problem were marked with ◯, and those with a problem of white turbidity with precipitation observed as a whole were marked with x. The results are shown in Tables 5 and 6.
表4、5から明らかなように、酒石酸の量が、水1質量部に対して0.02質量部ではミノキシジル5w/v%を完全に溶解することができず、酒石酸0.025質量部以上では析出が生じた。析出の生じない水1質量部に対して酒石酸量0.02質量部において、dl-リンゴ酸を組み合わせた比較例3は、析出が製剤全体に生じ白濁した。一方、表5、6から明らかなように、実施例1〜6及び11、12の外用組成物は、ミノキシジルが完全に溶解し、析出のない澄明な外用組成物が得られた。また、実施例7〜10に関しては、ミノキシジルが完全に溶解し、製剤中に極わずかに析出が生じたが、問題ない程度であった。 As is clear from Tables 4 and 5, when the amount of tartaric acid is 0.02 parts by mass with respect to 1 part by mass of water, minoxidil 5 w / v% cannot be completely dissolved, and 0.025 parts by mass or more of tartaric acid or more. Then precipitation occurred. In Comparative Example 3 in which dl-malic acid was combined at 0.02 parts by mass of tartaric acid with respect to 1 part by mass of water in which precipitation did not occur, precipitation occurred in the entire preparation and it became cloudy. On the other hand, as is clear from Tables 5 and 6, in the external compositions of Examples 1 to 6 and 11 and 12, minoxidil was completely dissolved, and a clear external composition without precipitation was obtained. Further, in Examples 7 to 10, minoxidil was completely dissolved and a very slight precipitation occurred in the formulation, but this was not a problem.
本発明により、酒石酸及び/又はその塩を含有したミノキシジル含有外用組成物において、ミノキシジルの溶解性を確保し、かつ結晶析出を抑制したミノキシジル含有外用組成物を提供することが可能になった。 INDUSTRIAL APPLICABILITY According to the present invention, it has become possible to provide a minoxidil-containing topical composition containing tartrate acid and / or a salt thereof, which ensures the solubility of minoxidil and suppresses crystal precipitation.
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