JP2024026455A - Composition for external use - Google Patents
Composition for external use Download PDFInfo
- Publication number
- JP2024026455A JP2024026455A JP2023215705A JP2023215705A JP2024026455A JP 2024026455 A JP2024026455 A JP 2024026455A JP 2023215705 A JP2023215705 A JP 2023215705A JP 2023215705 A JP2023215705 A JP 2023215705A JP 2024026455 A JP2024026455 A JP 2024026455A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- minoxidil
- present
- composition
- alcohol
- 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
- 239000000203 mixture Substances 0.000 title abstract description 54
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 abstract description 43
- 229960003632 minoxidil Drugs 0.000 abstract description 43
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 abstract description 39
- 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 abstract description 34
- FUWUEFKEXZQKKA-UHFFFAOYSA-N beta-thujaplicin Chemical compound CC(C)C=1C=CC=C(O)C(=O)C=1 FUWUEFKEXZQKKA-UHFFFAOYSA-N 0.000 abstract description 32
- 150000003839 salts Chemical class 0.000 abstract description 29
- 238000002360 preparation method Methods 0.000 abstract description 23
- 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 abstract description 17
- 229960003720 enoxolone Drugs 0.000 abstract description 17
- 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 abstract description 16
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 abstract description 16
- TUFYVOCKVJOUIR-UHFFFAOYSA-N alpha-Thujaplicin Natural products CC(C)C=1C=CC=CC(=O)C=1O TUFYVOCKVJOUIR-UHFFFAOYSA-N 0.000 abstract description 16
- 229940101267 panthenol Drugs 0.000 abstract description 16
- 235000020957 pantothenol Nutrition 0.000 abstract description 16
- 239000011619 pantothenol Substances 0.000 abstract description 16
- 229930007845 β-thujaplicin Natural products 0.000 abstract description 16
- 239000004480 active ingredient Substances 0.000 abstract description 15
- 229960000520 diphenhydramine Drugs 0.000 abstract description 15
- 239000002253 acid Substances 0.000 abstract description 11
- 238000002845 discoloration Methods 0.000 abstract description 7
- 150000005846 sugar alcohols Polymers 0.000 abstract description 7
- 238000002156 mixing Methods 0.000 abstract description 6
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 238000004040 coloring Methods 0.000 description 15
- 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 13
- 230000000052 comparative effect Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 8
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 6
- -1 arachyl alcohol Chemical compound 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 230000003779 hair growth Effects 0.000 description 5
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 5
- 230000000699 topical effect Effects 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- SWXVUIWOUIDPGS-UHFFFAOYSA-N diacetone alcohol Chemical compound CC(=O)CC(C)(C)O SWXVUIWOUIDPGS-UHFFFAOYSA-N 0.000 description 4
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- GOQYKNQRPGWPLP-UHFFFAOYSA-N heptadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 4
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 3
- 240000004371 Panax ginseng Species 0.000 description 3
- 235000002789 Panax ginseng Nutrition 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- ZQPPMHVWECSIRJ-MDZDMXLPSA-N elaidic acid Chemical compound CCCCCCCC\C=C\CCCCCCCC(O)=O ZQPPMHVWECSIRJ-MDZDMXLPSA-N 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
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 239000012085 test solution Substances 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
- 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
- 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
- 235000003261 Artemisia vulgaris Nutrition 0.000 description 2
- 240000006891 Artemisia vulgaris Species 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- FWKQNCXZGNBPFD-UHFFFAOYSA-N Guaiazulene Chemical compound CC(C)C1=CC=C(C)C2=CC=C(C)C2=C1 FWKQNCXZGNBPFD-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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 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
- 150000001298 alcohols Chemical class 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000000844 anti-bacterial effect Effects 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
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 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
- 229940082500 cetostearyl alcohol Drugs 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 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
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 235000008434 ginseng Nutrition 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 compound 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
- 230000003993 interaction Effects 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
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- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229940043348 myristyl alcohol Drugs 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
- SECPZKHBENQXJG-FPLPWBNLSA-N palmitoleic acid Chemical compound CCCCCC\C=C/CCCCCCCC(O)=O SECPZKHBENQXJG-FPLPWBNLSA-N 0.000 description 2
- REIUXOLGHVXAEO-UHFFFAOYSA-N pentadecan-1-ol Chemical compound CCCCCCCCCCCCCCCO REIUXOLGHVXAEO-UHFFFAOYSA-N 0.000 description 2
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 2
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- 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
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- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
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- 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
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- 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
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
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Landscapes
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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、グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分を配合したミノキシジル含有外用組成物の経時的な着色を抑制する技術に関する。 The present invention relates to an external composition containing minoxidil as an active ingredient. More specifically, a minoxidil-containing topical composition containing at least one active ingredient selected from the group consisting of glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salts. Related to technology for suppressing coloration over time.
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。
また、グリチルレチン酸は抗炎症作用があること（特許文献２）、パントテニールエチルエーテルは細胞賦活作用があること（特許文献３）、パンテノールは創傷治癒促進作用があること（特許文献４）、ヒノキチオールは抗菌作用があること（特許文献５）、ジフェンヒドラミンはかゆみ抑制作用があること（特許文献６）が報告されており、多くの育毛剤に用いられている。
Minoxidil, whose chemical name is 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, is known to be used as a hair growth agent (Patent Document 1), and has excellent hair growth and growth effects. There are many reports of drugs that exhibit this effect.
In addition, glycyrrhetinic acid has an anti-inflammatory effect (Patent Document 2), pantothenyl ethyl ether has a cell activating effect (Patent Document 3), and panthenol has a wound healing promoting effect (Patent Document 4). It has been reported that hinokitiol has an antibacterial effect (Patent Document 5) and that diphenhydramine has an itch suppressing effect (Patent Document 6), and these are used in many hair growth agents.
本発明者らは、優れた育毛剤を開発するため、ミノキシジルと酸を含有する組成物に、特定の有効成分、すなわちグリチルレチン酸、パントテニールエチルエーテル、パンテノール、ヒノキチオール、又は塩酸ジフェンヒドラミンを配合したミノキシジル含有外用組成物を製造し、安定性を評価したところ、意外にも、特定の有効成分の配合によりミノキシジル単独製剤よりも着色が増悪することがわかった。本発明は、グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分を配合したミノキシジル含有外用組成物において、製剤の着色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。 In order to develop an excellent hair growth agent, the present inventors combined specific active ingredients, namely glycyrrhetinic acid, pantothenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine hydrochloride, into a composition containing minoxidil and an acid. When a minoxidil-containing topical composition was manufactured and its stability was evaluated, it was surprisingly found that the addition of a specific active ingredient worsened the discoloration compared to a minoxidil-only preparation. The present invention provides a minoxidil-containing topical composition containing at least one active ingredient selected from the group consisting of glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salts, An object of the present invention is to provide a minoxidil-containing external composition that suppresses coloring of the preparation.
今までに２ｗ／ｗ％以上のミノキシジルと、グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、又はジフェンヒドラミン及び／又はその塩との間に、製剤の着色増悪に影響を与えるような相互作用を生じるか否かについて、報告された例はない。 Up to now, there has been no interaction between 2 w/w % or more of minoxidil and glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine and/or its salts, which affect the discoloration of the preparation. There are no reports on whether such an interaction occurs.
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、グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、又はジフェンヒドラミン及び／又はその塩を配合したミノキシジル含有外用組成物を製造する場合は、特定の多価アルコールを選択することにより、経時的な製剤の着色を抑制したミノキシジル含有外用組成物が製造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 intensive studies to solve the above problems, the present inventors have found that a minoxidil-containing topical product containing glycyrrhetinic acid and/or its salt, pantothenyl ethyl ether, panthenol, hinokitiol, or diphenhydramine and/or its salt The present inventors have discovered that when producing a composition, by selecting a specific polyhydric alcohol, it is possible to produce a minoxidil-containing external composition that suppresses coloring of the preparation over time, and has completed the present invention.
すなわち本発明は、
（１）ａ）２ｗ／ｗ％以上のミノキシジル、
ｂ）グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分、
ｃ）プロピレングリコール、及び
ｄ）酸を含有することを特徴とする外用組成物、
（２）ミノキシジルの濃度が５ｗ／ｗ％以上である（１）に記載の外用組成物、
（３）ａ）２ｗ／ｗ％以上のミノキシジル、
ｂ）グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分、
ｃ）プロピレングリコール、及び
ｄ）酸を混合して混合物を調製する工程と、
前記混合物にｅ）水、ｆ）低級アルコールを加えて全量調製する工程を含むことを特徴とする外用組成物の製造方法、
である。
That is, the present invention
(1) a) 2 w/w% or more of minoxidil,
b) at least one active ingredient selected from the group consisting of glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salts;
A composition for external use, characterized in that it contains c) propylene glycol, and d) an acid;
(2) the external composition according to (1), wherein the concentration of minoxidil is 5 w/w% or more;
(3) a) 2 w/w% or more of minoxidil;
b) at least one active ingredient selected from the group consisting of glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salts;
c) propylene glycol, and d) acid to form a mixture;
A method for producing a composition for external use, comprising the step of adding e) water and f) lower alcohol to the mixture to prepare the total amount;
It is.
本発明により、グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分を配合した２ｗ／ｗ％以上のミノキシジル含有外用組成物において、製剤の経時的な着色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。 According to the present invention, minoxidil containing at least 2 w/w % of at least one active ingredient selected from the group consisting of glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salts It has now become possible to provide a minoxidil-containing external composition in which discoloration of the preparation over time is suppressed.
本発明によれば、２ｗ／ｗ％以上のミノキシジル、グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分、プロピレングリコール、及び酸を含有する外用組成物は、ミノキシジル製剤の着色を抑制したものとなる。 According to the present invention, 2 w/w % or more of at least one active ingredient selected from the group consisting of minoxidil, glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salts. An external composition containing minoxidil, propylene glycol, and an acid suppresses discoloration of a minoxidil preparation.
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、本発明によれば、ミノキシジルの含有量は２ｗ／ｗ％以上であり、さらに好ましくは３ｗ／ｗ％以上であり、さらにより好ましくは５ｗ／ｗ％以上である。５ｗ／ｗ％以上となると、より製剤の着色が進行するため、本発明ではこの範囲で実施する意義が大きい。 The minoxidil used in the external composition of the present invention can be of a quality commonly used in pharmaceuticals. Further, according to the present invention, the content of minoxidil is 2 w/w% or more, more preferably 3 w/w% or more, and even more preferably 5 w/w% or more. When the content is 5 w/w% or more, the coloring of the preparation progresses further, so in the present invention, it is significant to implement the content within this range.
本発明の外用組成物において用いる多価アルコールは、本発明の効果である、製剤の経時的な着色を抑制する点からプロピレングリコールである。プロピレングリコールの配合量は、全組成物中好ましくは２～５５ｗ／ｗ％であり、より好ましくは２～３５ｗ／ｗ％であり、さらに好ましくは２～１５ｗ／ｗ％である。本発明の外用組成物中には、本発明の効果を損なわない範囲でプロピレングリコール以外の多価アルコールを含んでもよいが、グリセリン、ポリエチレングリコール、ジプロピレングリコールは配合しない方が本発明の効果の点から好ましく、プロピレングリコールのみを配合することが本発明の効果の点から最も好ましい。 The polyhydric alcohol used in the external composition of the present invention is propylene glycol because it suppresses discoloration of the preparation over time, which is an effect of the present invention. The amount of propylene glycol in the entire composition is preferably 2 to 55 w/w%, more preferably 2 to 35 w/w%, even more preferably 2 to 15 w/w%. The external composition of the present invention may contain polyhydric alcohols other than propylene glycol as long as they do not impair the effects of the present invention, but the effects of the present invention will be better if glycerin, polyethylene glycol, and dipropylene glycol are not included. It is preferable from this point of view, and it is most preferable from the point of view of the effects of the present invention to blend only propylene glycol.
ミノキシジルを基剤中に溶解させるためには酸を用いることが知られている。本発明の外用組成物において用いる酸としては、本発明の外用組成物の液性を７以下に調節する成分が好ましく、無機酸もしくは炭素数が６以下の有機酸が挙げられる。具体的にはリン酸、クエン酸、乳酸、塩酸、酢酸、硫酸、硝酸、酒石酸、マレイン酸、リンゴ酸、グルコン酸であり、好ましくはリン酸、クエン酸、乳酸、酒石酸である。これら酸を１種又は２種以上組み合わせてもよい。 It is known to use an acid to dissolve minoxidil in a base. The acid used in the external composition of the present invention is preferably a component that adjusts the liquid properties of the external composition of the present invention to 7 or less, and examples thereof include inorganic acids and organic acids having 6 or less carbon atoms. Specifically, they are phosphoric acid, citric acid, lactic acid, hydrochloric acid, acetic acid, sulfuric acid, nitric acid, tartaric acid, maleic acid, malic acid, and gluconic acid, and preferably phosphoric acid, citric acid, lactic acid, and tartaric acid. These acids may be used alone or in combination.
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４．０～９．５の範囲に調整することが好ましく、５．０～７．０の範囲がさらに好ましい。さらに、ｐＨの上限としては、好ましくは６．５未満であり、より好ましくは６．３以下、さらに好ましくは６．１以下である。 In addition, the external composition of the present invention has a pH of 4.0 to 9.5 in view of the stability of minoxidil, the main drug ingredient, the irritation to the skin during use, the permeability of the drug, and the feeling of use. It is preferable to adjust it to a range of 5.0 to 7.0, and more preferably a range of 5.0 to 7.0. Furthermore, the upper limit of pH is preferably less than 6.5, more preferably 6.3 or less, and even more preferably 6.1 or less.
本発明の外用組成物において用いるグリチルレチン酸及び／又はその塩の配合量は、本発明の着色を抑制するとの課題の点から外用組成物中０．０１～１ｗ／ｗ％が好ましく、０．０２～０．５ｗ／ｗ％がより好ましく、０．０５～０．１ｗ／ｗ％が更に好ましく、また、ミノキシジル１質量部に対して０．０２質量部以上が好ましい。パントテニールエチルエーテルの配合量は、本発明の着色を抑制するとの課題の点から外用組成物中０．１～５ｗ／ｗ％が好ましく、０．２～２ｗ／ｗ％がより好ましく、０．２～１ｗ／ｗ％が更に好ましく、また、ミノキシジル１質量部に対して０．２質量部以上が好ましい。パンテノールの配合量は、本発明の着色を抑制するとの課題の点から外用組成物中０．１～５ｗ／ｗ％が好ましく、０．２～２ｗ／ｗ％がより好ましく、０．２～１ｗ／ｗ％が更に好ましく、また、ミノキシジル１質量部に対して０．２質量部以上が好ましい。ヒノキチオールの配合量は、本発明の着色を抑制するとの課題の点から外用組成物中０．０１～０．１ｗ／ｗ％が好ましく、０．０１～０．０５ｗ／ｗ％がより好ましく、０．０２～０．０５ｗ／ｗ％が更に好ましく、また、ミノキシジル１質量部に対して０．０１質量部以上が好ましい。ジフェンヒドラミン及び／又はその塩の配合量は、本発明の着色を抑制するとの課題の点から外用組成物中０．０１～１ｗ／ｗ％が好ましく、０．０２～０．５ｗ／ｗ％がより好ましく、０．０５～０．１ｗ／ｗ％が更に好ましく、また、ミノキシジル１質量部に対して０．０２質量部以上が好ましい。 The amount of glycyrrhetinic acid and/or its salt used in the external composition of the present invention is preferably 0.01 to 1 w/w%, and 0.02% in view of the problem of suppressing coloring of the present invention. ~0.5 w/w% is more preferred, 0.05~0.1 w/w% is even more preferred, and 0.02 parts by mass or more is preferred per 1 part by mass of minoxidil. The blending amount of pantothenyl ethyl ether is preferably 0.1 to 5 w/w%, more preferably 0.2 to 2 w/w%, and 0.1 to 5 w/w%, more preferably 0.2 to 2 w/w%, in view of the problem of suppressing coloring of the present invention. It is more preferably 2 to 1 w/w%, and more preferably 0.2 parts by mass or more per 1 part by mass of minoxidil. The blending amount of panthenol in the external composition is preferably 0.1 to 5 w/w%, more preferably 0.2 to 2 w/w%, and 0.2 to 2 w/w%, in view of the problem of suppressing coloring of the present invention. It is more preferably 1 w/w%, and more preferably 0.2 parts by mass or more per 1 part by mass of minoxidil. The amount of hinokitiol in the external composition is preferably 0.01 to 0.1 w/w%, more preferably 0.01 to 0.05 w/w%, and 0.01 to 0.1 w/w%, more preferably 0.01 to 0.05 w/w%, from the viewpoint of suppressing coloring of the present invention. It is more preferably 0.02 to 0.05 w/w%, and more preferably 0.01 part by mass or more per 1 part by mass of minoxidil. The blending amount of diphenhydramine and/or its salt is preferably 0.01 to 1 w/w% in the external composition, more preferably 0.02 to 0.5 w/w%, in view of the problem of suppressing coloring of the present invention. It is preferably 0.05 to 0.1 w/w%, more preferably 0.02 parts by mass or more per 1 part by mass of minoxidil.
本発明の外用組成物には、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、外用組成物中０．０５～１０ｗ／ｗ％が好ましく、０．１～５ｗ／ｗ％がより好ましく、０．２５～１．５ｗ／ｗ％が更に好ましい。 The external composition of the present invention may further contain a higher alcohol if necessary. Examples of higher alcohols include diacetone alcohol having 6 to 24 carbon atoms, caproyl alcohol, caprylyl alcohol, caprylic alcohol, lauryl alcohol, tridecanol, myristyl alcohol, pentadecanol, cetyl alcohol, hexyldecanol, isocetyl alcohol, More preferred are cetostearyl alcohol, heptadecanol, stearyl alcohol, oleyl alcohol, isostearyl alcohol, octyldecanol, nonadecanol, arachyl alcohol, octyldodecanol, henicosanol, behenyl alcohol, and decyltetradecanol, among which diacetone alcohol, More preferred are lauryl alcohol, myristyl alcohol, cetyl alcohol, hexyldecanol, cetostearyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, aracyl alcohol, octyldodecanol, behenyl alcohol, and decyltetradecanol. The higher alcohols of the present invention may be used alone or in combination of two or more. The content of higher alcohol in the external composition is preferably 0.05 to 10 w/w%, more preferably 0.1 to 5 w/w%, even more preferably 0.25 to 1.5 w/w%.
本発明の外用組成物には、更に必要により低級アルコールや水を配合することができる。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。低級アルコールの含有量は、全組成物中２０ｗ／ｗ％以上が好ましく、より好ましくは３０ｗ／ｗ％以上であり、より好ましくは３５ｗ／ｗ％以上であり、更に好ましくは５０ｗ／ｗ％以上である。水の配合量は、２～７５ｗ／ｗ％が好ましく、より好ましくは５～５０ｗ／ｗ％である。 The external composition of the present invention may further contain a lower alcohol or water if necessary. The lower alcohol preferably has 1 to 5 carbon atoms, such as ethanol and isopropanol, and a combination of these may be used. The content of the lower alcohol is preferably 20 w/w% or more in the entire composition, more preferably 30 w/w% or more, more preferably 35 w/w% or more, and still more preferably 50 w/w% or more. be. The amount of water added is preferably 2 to 75 w/w%, more preferably 5 to 50 w/w%.
本発明の外用組成物には、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。高級脂肪酸の配合量は、全組成物中好ましくは０．１～１０ｗ／ｗ％であり、より好ましくは１～６ｗ／ｗ％である。 The external composition of the present invention may further contain higher fatty acids if necessary. Examples of higher fatty acids preferably include those having 10 to 22 carbon atoms, such as isostearic acid, oleic acid, stearic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, linoleic acid, linolenic acid, and elaidic acid. , arachidic acid, arachidonic acid, behenic acid, eicosapentaenoic acid, docosahexaenoic acid, etc., and these may be used alone or in combination of two or more. Among these, those having 18 carbon atoms are preferred, and isostearic acid or oleic acid is particularly preferred. The content of higher fatty acids is preferably 0.1 to 10 w/w%, more preferably 1 to 6 w/w% in the total composition.
本発明の外用組成物には、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 topical composition of the present invention can ensure the solubility of minoxidil without adding a surfactant. , it is preferable that it substantially not contain a surfactant.
本発明の外用組成物においては、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, various active ingredients and auxiliary ingredients used in general external preparations can be blended within a range that does not impair the effects of the present invention. For example, excipients, hair-growth ingredients (6-benzylaminopurine, adenosine, pentadecanoic acid glyceride, Heshuu Tori, etc.), vasodilators (carpronium chloride, benzyl nicotinate, Oriental ginseng extract, Panax ginseng extract, Panax ginseng tincture, capsicum tincture, etc.), antihistamines (isothipenzyl hydrochloride, etc.), anti-inflammatory agents (guaiazulene, etc.), keratolytic agents (urea, salicylic acid, etc.), bactericides (chlorhexidine gluconate, isopropylmethylphenol, quaternary ammonium salts, piroctonola) moisturizers (hyaluronic acid or its salts, chondroitin sulfate, etc.), various plants and animals (yew, botanpi, licorice, hypericum, tsuji, loquat, mugwort, comfrey, reedica, saffron, sardine, rosemary, sage, mokko) , sagebrush, hops, placenta, saw palmetto, pumpkin seed, etc.), vitamins (retinyl acetate, ascorbic acid, thiamine nitrate, cyanocobalamin, biotin, etc.), antioxidants (dibutylhydroxytoluene, sodium pyrosulfite, tocopherol, edetol, etc.) acid sodium, ascorbic acid, isopropyl gallate, etc.), solubilizing agents (diisopropyl adipate, isopropyl myristate, various vegetable oils, various animal oils, alkyl glyceryl ethers, hydrocarbons, etc.), metabolic activators, gelling agents (highly water-soluble Commonly used ingredients such as molecules, adhesives, fragrances, cooling agents (mentha oil, camphor, etc.), dyes, etc. can be blended.
本発明の外用組成物の剤形の例としては、液剤、ローション剤等が挙げられる。
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。
Examples of dosage forms of the external composition of the present invention include solutions, lotions, and the like.
The external composition of the present invention is prepared by containing the above-mentioned 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 thus obtained external composition of the present invention can be used as a skin preparation such as a hair preparation, an eyelash preparation, an eyebrow preparation, and the like.
本発明の外用組成物の製造方法としては、例えばａ）２ｗ／ｗ％以上のミノキシジル、ｂ）グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分、ｃ）プロピレングリコール、及びｄ）酸を混合して混合物を調製し、その混合物にｅ）水及びｆ）低級アルコールを加えて全量調製する方法、ａ）２ｗ／ｗ％以上のミノキシジル、ｂ）グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分、ｃ）プロピレングリコール、ｄ）酸、ｅ）水を混合して混合物を調製し、その混合物にｆ）低級アルコールを加えて全量調製する方法などが挙げられる。 The method for producing the external composition of the present invention includes, for example, a) 2 w/w % or more of minoxidil, b) glycyrrhetinic acid and/or its salt, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salt. A method of preparing a mixture by mixing at least one active ingredient selected from the group consisting of c) propylene glycol, and d) acid, and adding e) water and f) lower alcohol to the mixture to prepare the total amount, a. ) 2 w/w % or more of minoxidil, b) at least one active ingredient selected from the group consisting of glycyrrhetinic acid and/or its salts, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salts, c) Examples include a method of preparing a mixture by mixing propylene glycol, d) acid, and e) water, and adding f) lower alcohol to the mixture to prepare the total amount.
以下に、実施例、比較例及び参考例を記載し、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。 EXAMPLES Below, the present invention will be described in more detail with reference to Examples, Comparative Examples, and Reference Examples, but the present invention is not limited to these Examples in any way.
（実施例１～１０、比較例１～１７及び参考例１）
実施例１～１０、比較例１～１７及び参考例１の処方を表１～２に示す。表１～２に記載の各成分を混合、撹拌して溶解し、エタノールを加えて全量１００ｇとして製剤を調製した。
(Examples 1 to 10, Comparative Examples 1 to 17 and Reference Example 1)
The formulations of Examples 1 to 10, Comparative Examples 1 to 17, and Reference Example 1 are shown in Tables 1 to 2. Each component listed in Tables 1 and 2 was mixed, stirred and dissolved, and ethanol was added to make a total amount of 100 g to prepare a preparation.
（試験方法１：熱安定性試験－１）
実施例１、比較例１～３及び参考例１の試験液を６５℃（相対湿度成り行き）で３日間保管後、製剤を目視で観察し、色調を確認した。
(Test method 1: Thermal stability test-1)
After storing the test solutions of Example 1, Comparative Examples 1 to 3, and Reference Example 1 at 65° C. (relative humidity varies) for 3 days, the preparations were visually observed to confirm the color tone.
（結果）
表３から明らかなように、多価アルコールにプロピレングリコールを配合したミノキシジル含有製剤（実施例１）の着色は経時的に進行しなかった（無色）が、多価アルコールにプロピレングリコール以外を配合したミノキシジル含有製剤（比較例１～３）の着色は経時的に進行した（微黄色）。
(result)
As is clear from Table 3, the coloring of the minoxidil-containing preparation (Example 1), which was a combination of polyhydric alcohol and propylene glycol, did not progress over time (colorless); The coloring of the minoxidil-containing preparations (Comparative Examples 1 to 3) progressed over time (slight yellow).
（試験方法２：熱安定性試験－２）
実施例２、及び比較例４～５の試験液を６５℃（相対湿度成り行き）で５日間保管後、製剤を目視で観察し、色調を確認した。
(Test method 2: Thermal stability test-2)
After storing the test solutions of Example 2 and Comparative Examples 4 and 5 at 65° C. (relative humidity varies) for 5 days, the preparations were visually observed to confirm the color tone.
（結果）
表４から明らかなように、多価アルコールにプロピレングリコールを配合したミノキシジル含有製剤（実施例２）の着色は経時的に進行しなかった（無色）が、多価アルコールにプロピレングリコール以外を配合したミノキシジル含有製剤（比較例４～５）の着色は経時的に進行した（微黄色）。
(result)
As is clear from Table 4, the coloring of the minoxidil-containing formulation (Example 2), which was a combination of polyhydric alcohol and propylene glycol, did not progress over time (colorless); The coloring of the minoxidil-containing preparations (Comparative Examples 4 to 5) progressed over time (slight yellow).
また，同じ微黄色でも、グリチルレチン酸の濃度が高い製剤の方が強い色調を示した。 Furthermore, even though the color was slightly yellow, the formulation with a higher concentration of glycyrrhetinic acid had a stronger color tone.
（試験方法３：熱安定性試験－３）
実施例３～１０、比較例６～１７及び参考例１の試験液を６５℃（相対湿度成り行き）で５日間保管後、製剤を目視で観察し、色調を確認した。
(Test method 3: Thermal stability test-3)
After storing the test solutions of Examples 3 to 10, Comparative Examples 6 to 17, and Reference Example 1 at 65°C (relative humidity varies) for 5 days, the formulations were visually observed to confirm the color tone.
（結果）
表５から明らかなように、多価アルコールにプロピレングリコールを配合したミノキシジル含有製剤（実施例３～１０）の着色は経時的に進行しなかった（無色）が、多価アルコールにプロピレングリコール以外を配合したミノキシジル含有製剤（比較例６～１７）の着色は経時的に進行した（微黄色又は黄色）。
(result)
As is clear from Table 5, the coloring of minoxidil-containing preparations (Examples 3 to 10) containing polyhydric alcohol and propylene glycol did not progress over time (colorless); The coloring of the blended minoxidil-containing preparations (Comparative Examples 6 to 17) progressed over time (slightly yellow or yellow).
本発明により、グリチルレチン酸及び／又はその塩、パントテニールエチルエーテル、パンテノール、ヒノキチオール、ジフェンヒドラミン及び／又はその塩からなる群から選ばれる少なくとも１種の有効成分を配合したミノキシジル含有外用組成物において、製剤の経時的な着色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。 According to the present invention, in a minoxidil-containing topical composition containing at least one active ingredient selected from the group consisting of glycyrrhetinic acid and/or its salt, pantothenyl ethyl ether, panthenol, hinokitiol, diphenhydramine and/or its salt, It has become possible to provide a minoxidil-containing external composition that suppresses coloring of the preparation over time.
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| JP2021113393A JP2021165305A (en) | 2016-09-15 | 2021-07-08 | Composition for external use |
| JP2022178186A JP2022190158A (en) | 2016-09-15 | 2022-11-07 | Composition for external use |
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| DE3778027D1 (en) * | 1986-09-05 | 1992-05-07 | Upjohn Co | SEBUM SOLVING, NOT AQUEOUS MINOXIDIL FORMULATION. |
| JP4467085B2 (en) * | 1996-01-05 | 2010-05-26 | 大正製薬株式会社 | Hinokitiol-containing composition |
| JPH11263727A (en) * | 1997-12-03 | 1999-09-28 | Taisho Pharmaceut Co Ltd | Minoxidil formulated liquid preparation composition |
| AUPP310798A0 (en) | 1998-04-22 | 1998-05-14 | Soltec Research Pty Ltd | Vehicle system for a composition comprising a piperidinopyrimidine derivative |
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