JP7467037B2 - External Composition - Google Patents
External Composition Download PDFInfo
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- JP7467037B2 JP7467037B2 JP2019117409A JP2019117409A JP7467037B2 JP 7467037 B2 JP7467037 B2 JP 7467037B2 JP 2019117409 A JP2019117409 A JP 2019117409A JP 2019117409 A JP2019117409 A JP 2019117409A JP 7467037 B2 JP7467037 B2 JP 7467037B2
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- allantoin
- topical composition
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- 239000000203 mixture Substances 0.000 title claims description 85
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 claims description 116
- 230000000699 topical effect Effects 0.000 claims description 61
- 229960000458 allantoin Drugs 0.000 claims description 57
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 claims description 56
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 49
- 239000004202 carbamide Substances 0.000 claims description 25
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- -1 aluminum chlorhydrate Chemical compound 0.000 claims description 7
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 4
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 229910052782 aluminium Inorganic materials 0.000 claims 3
- 229940009840 aluminum chlorhydrate Drugs 0.000 claims 2
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 claims 1
- 235000004866 D-panthenol Nutrition 0.000 claims 1
- 239000011703 D-panthenol Substances 0.000 claims 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims 1
- 229960004311 betamethasone valerate Drugs 0.000 claims 1
- SNHRLVCMMWUAJD-SUYDQAKGSA-N betamethasone valerate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O SNHRLVCMMWUAJD-SUYDQAKGSA-N 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 150000007942 carboxylates Chemical group 0.000 claims 1
- BMCQMVFGOVHVNG-TUFAYURCSA-N cortisol 17-butyrate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CO)(OC(=O)CCC)[C@@]1(C)C[C@@H]2O BMCQMVFGOVHVNG-TUFAYURCSA-N 0.000 claims 1
- 229960001524 hydrocortisone butyrate Drugs 0.000 claims 1
- DGYSDXLCLKPUBR-SLPNHVECSA-N prednisolone valerate acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(C)=O)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O DGYSDXLCLKPUBR-SLPNHVECSA-N 0.000 claims 1
- 229950008480 prednisolone valerate acetate Drugs 0.000 claims 1
- 238000003860 storage Methods 0.000 description 18
- 239000004615 ingredient Substances 0.000 description 13
- 238000009472 formulation Methods 0.000 description 11
- 239000004471 Glycine Substances 0.000 description 10
- 238000000354 decomposition reaction Methods 0.000 description 8
- 210000003491 skin Anatomy 0.000 description 8
- 239000002738 chelating agent Substances 0.000 description 7
- 150000005846 sugar alcohols Polymers 0.000 description 7
- 239000002562 thickening agent Substances 0.000 description 7
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 235000004279 alanine Nutrition 0.000 description 6
- 230000001139 anti-pruritic effect Effects 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000000654 additive Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000003020 moisturizing effect Effects 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 230000000087 stabilizing effect Effects 0.000 description 3
- 230000017423 tissue regeneration Effects 0.000 description 3
- 229940058015 1,3-butylene glycol Drugs 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 235000019437 butane-1,3-diol Nutrition 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229960001484 edetic acid Drugs 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 230000007721 medicinal effect Effects 0.000 description 2
- 239000007764 o/w emulsion Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 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 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- XPFCZYUVICHKDS-UHFFFAOYSA-N 3-methylbutane-1,3-diol Chemical compound CC(C)(O)CCO XPFCZYUVICHKDS-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- HDVDLQFPDLTOSI-UHFFFAOYSA-L O[AlH]O Chemical compound O[AlH]O HDVDLQFPDLTOSI-UHFFFAOYSA-L 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 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
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- RKFMOTBTFHXWCM-UHFFFAOYSA-M [AlH2]O Chemical compound [AlH2]O RKFMOTBTFHXWCM-UHFFFAOYSA-M 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 239000003899 bactericide agent Substances 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
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000037336 dry skin Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000003205 fragrance Substances 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
- 238000004128 high performance liquid chromatography Methods 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
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920002432 poly(vinyl methyl ether) polymer Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000001737 promoting effect Effects 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
- 231100000241 scar Toxicity 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- 239000013535 sea water Substances 0.000 description 1
- 239000003009 skin protective agent Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000007762 w/o emulsion Substances 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
- 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 1
Description
本発明は、アラントイン及び／又はその誘導体、並びに尿素を含み、アラントイン及び／又はその誘導体の分解が抑制され、優れた保存安定性を有する外用組成物に関する。 The present invention relates to a composition for external use that contains allantoin and/or its derivatives, and urea, in which the decomposition of allantoin and/or its derivatives is inhibited and that has excellent storage stability.
アラントインには、組織修復賦活作用、抗炎症作用、鎮痒作用等があり、外用組成物に使用されている。また、尿素には、角質中での水分保持、細胞賦活作用、抗菌作用、鎮痒作用等があり、皮膚外用医薬品や化粧料等の外用組成物に使用されている。 Allantoin has tissue repair activation, anti-inflammatory, and antipruritic effects, and is used in external compositions. Urea retains moisture in the stratum corneum, activates cells, has antibacterial and antipruritic effects, and is used in external compositions such as skin medicines and cosmetics.
近年、外用組成物に対する機能性の向上が強く求められるようになっており、アラントイン及び／又はその誘導体、並びに尿素の機能性に着目し、これらの成分を併用することにより機能性を向上させた外用組成物についても提案されている。例えば、特許文献１には、所定量のアラントイン、尿素、１，３－ブチレングリコール、ポリグリセリン、及び海洋深層水を含む外用組成物が、アトピー性皮膚炎の予防や治療などに有効であることが開示されている。 In recent years, there has been a strong demand for improving the functionality of topical compositions, and topical compositions have been proposed that focus on the functionality of allantoin and/or its derivatives, and urea, and that use these ingredients in combination to improve their functionality. For example, Patent Document 1 discloses that a topical composition containing specified amounts of allantoin, urea, 1,3-butylene glycol, polyglycerin, and deep sea water is effective in preventing and treating atopic dermatitis.
一方、アラントインはｐＨ６以上になると分解され易いという欠点がある。また、尿素は、僅かでも分解するとアルカリ性を呈し、アラントインを分解させ易くするという特性がある。そのため、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物では、アラントインの分解を抑制し、保存安定性を高める製剤技術が要求されるが、従来、このような製剤技術については十分な検討がなされていない。 On the other hand, allantoin has the disadvantage that it is easily decomposed at a pH of 6 or higher. In addition, urea has the property that it becomes alkaline even when decomposed even slightly, making allantoin more easily decomposed. Therefore, for topical compositions containing allantoin and/or its derivatives, and urea, formulation technology is required that suppresses the decomposition of allantoin and enhances storage stability, but such formulation technology has not been sufficiently studied to date.
本発明者は、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物を開発すべく種々検討を行ったところ、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物では、保存によりｐＨが上昇してアラントインが分解されるため、保存安定性が著しく悪いという知見を得た。 The present inventors conducted various studies to develop a topical composition containing allantoin and/or its derivatives, and urea, and discovered that the storage stability of a topical composition containing allantoin and/or its derivatives, and urea is extremely poor because the pH increases during storage and allantoin is decomposed.
そこで、本発明の目的は、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物において、アラントイン及び／又はその誘導体の分解を抑制でき、保存安定性を向上させる製剤技術を提供することである。 The object of the present invention is to provide a formulation technology that can suppress the decomposition of allantoin and/or its derivatives and improve storage stability in a topical composition containing allantoin and/or its derivatives, and urea.
本発明者は、前記課題を解決すべく鋭意検討を行ったところ、アラントイン及び／又はその誘導体、並びに尿素と共に、グリシン及びアラニンを含有させた外用組成物は、アラントイン及び／又はその誘導体の分解を抑制でき、アラントイン及び／又はその誘導体の保存安定性が格段に向上することを見出した。本発明は、かかる知見に基づいて更に検討を重ねることにより完成したものである。 The present inventors conducted extensive research to solve the above problems and discovered that a topical composition containing allantoin and/or its derivatives, urea, glycine and alanine can inhibit the decomposition of allantoin and/or its derivatives, and significantly improve the storage stability of allantoin and/or its derivatives. The present invention was completed through further research based on this knowledge.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項１． (A)アラントイン及び／又はその誘導体、(B)尿素、(C)グリシン、並びに(D)アラニンを含有する、外用組成物。
項２． 前記(A)成分がアラントインである、項１に記載の外用組成物。
項３． 更に、水を含む、項１又は２に記載の外用組成物。
That is, the present invention provides the following aspects.
Item 1. A composition for external use comprising (A) allantoin and/or a derivative thereof, (B) urea, (C) glycine, and (D) alanine.
Item 2. The composition for external use according to Item 1, wherein the component (A) is allantoin.
Item 3. The composition for external use according to Item 1 or 2, further comprising water.
本発明の外用組成物によれば、アラントイン及び／又はその誘導体、並びに尿素を含んでいながらも、アラントイン及び／又はその誘導体の分解を抑制でき、格段に優れた保存安定性を備えることができる。 The topical composition of the present invention contains allantoin and/or its derivatives, as well as urea, and yet is capable of inhibiting the decomposition of allantoin and/or its derivatives, and thus exhibits significantly superior storage stability.
１．外用組成物
本発明の外用組成物は、アラントイン及び／又はその誘導体（(A)成分と表記することもある）、尿素（(B)成分と表記することもある）、グリシン（(C)成分と表記することもある）、並びにアラニン（(D)成分と表記することもある）を含有することを特徴とする。以下、本発明の外用組成物について詳述する。
1. Topical Composition The topical composition of the present invention is characterized by containing allantoin and/or its derivatives (sometimes referred to as component (A)), urea (sometimes referred to as component (B)), glycine (sometimes referred to as component (C)), and alanine (sometimes referred to as component (D)). The topical composition of the present invention will be described in detail below.
(A)アラントイン及び／又はその誘導体
本発明の外用組成物は、アラントイン及び／又はその誘導体を含有する。アラントインは、５－ウレイドヒダントインとも称される化合物であり、組織修復賦活作用、抗炎症作用、鎮痒作用等を有することが知られている公知の成分である。
(A) Allantoin and/or its derivatives The topical composition of the present invention contains allantoin and/or its derivatives. Allantoin is a compound also known as 5-ureidohydantoin, and is a known ingredient known to have tissue repair activating effects, anti-inflammatory effects, antipruritic effects, etc.
アラントインの誘導体としては、薬学的又は香粧学的に許容できることを限度として特に制限されないが、具体的には、アラントインクロルヒドロキシアルミニウム、アラントインヒドロキシアルミニウム、アラントインジヒドロキシアルミニウム、アラントインクロルヒドロキシアルミニウム等が挙げられる。これらのアラントインの誘導体は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The allantoin derivatives are not particularly limited as long as they are pharma- ceutically or cosmetically acceptable, but specific examples include allantoin chlorhydroxyaluminum, allantoin hydroxyaluminum, allantoin dihydroxyaluminum, allantoin chlorhydroxyaluminum, etc. These allantoin derivatives may be used alone or in combination of two or more.
本発明の外用組成物では、(A)成分として、アラントイン又はその誘導体のいずれか一方のみを使用してもよく、またこれらを組み合わせて使用してもよい。(A)成分の中でも、その安定化効果をより一層向上させるという観点から、好ましくはアラントインが挙げられる。 In the topical composition of the present invention, either allantoin or its derivatives may be used alone as component (A), or these may be used in combination. Of the components (A), allantoin is preferred from the viewpoint of further improving the stabilizing effect.
本発明の外用組成物における(A)成分の含有量については、特に制限されず、付与すべき薬効、外用組成物の形態等に応じて適宜設定されるが、例えば０．０５～２重量％、好ましくは０．１～２重量％、更に好ましくは０．２～１．５重量％が挙げられる。 The content of component (A) in the topical composition of the present invention is not particularly limited and is appropriately set depending on the medicinal effect to be imparted, the form of the topical composition, etc., but may be, for example, 0.05 to 2% by weight, preferably 0.1 to 2% by weight, and more preferably 0.2 to 1.5% by weight.
［（B)尿素］
本発明の外用組成物は、尿素を含有する。尿素は、保湿作用、細胞賦活作用、抗菌作用、鎮痒作用等を有することが知られている公知の成分である。
[(B) Urea]
The topical composition of the present invention contains urea. Urea is a known ingredient known to have moisturizing, cell activating, antibacterial, and antipruritic effects.
本発明の外用組成物における(B)成分の含有量については、付与すべき薬効、外用組成物の形態等に応じて適宜設定されるが、１～３０重量％、好ましくは２．５～２５重量％、更に好ましくは５～２０重量％が挙げられる。 The content of component (B) in the topical composition of the present invention is appropriately set depending on the medicinal effect to be imparted, the form of the topical composition, etc., but may be 1 to 30% by weight, preferably 2.5 to 25% by weight, and more preferably 5 to 20% by weight.
本発明の外用組成物において、(A)成分に対する(B)成分の比率については、これらの成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(B)成分が０．５～６００重量部、好ましくは１．５～２５０重量部、更に好ましくは５～２００重量部が挙げられる。 In the topical composition of the present invention, the ratio of component (B) to component (A) is determined according to the content of each of these components, but for example, the ratio of component (B) is 0.5 to 600 parts by weight, preferably 1.5 to 250 parts by weight, and more preferably 5 to 200 parts by weight per part by weight of component (A).
［(C)グリシン及び(D)アラニン］
本発明の外用組成物は、グリシン及びアラニンを含有する。アラントイン又はその誘導体、並びに尿素を含む外用組成物では、保存によりアラントイン及び／又はその誘導体の分解が生じ、保存安定性が悪くなるが、本発明の外用組成物では、これらの成分に加えてグリシン及びアラニンを含むことにより、アラントイン及び／又はその誘導体の分解を抑制でき、保存安定性を格段に向上させることが可能なる。グリシン及びアラニンは、アミノ酸として公知の成分である。
[(C) glycine and (D) alanine]
The topical composition of the present invention contains glycine and alanine.In the topical composition containing allantoin or its derivative and urea, allantoin and/or its derivative decompose during storage, and storage stability is deteriorated.However, in the topical composition of the present invention, by containing glycine and alanine in addition to these components, the decomposition of allantoin and/or its derivative can be suppressed, and storage stability can be significantly improved.Glycine and alanine are known components as amino acids.
本発明の外用組成物において、(C)成分と(D)成分の比率については、特に制限されないが、例えば、(C)成分１重量部当たり、(D)成分が０．０５～２０重量部、好ましくは０．１～２０重量部、更に好ましくは０．５～１０重量部が挙げられる。 In the topical composition of the present invention, the ratio of component (C) to component (D) is not particularly limited, but for example, the ratio of component (D) is 0.05 to 20 parts by weight, preferably 0.1 to 20 parts by weight, and more preferably 0.5 to 10 parts by weight per 1 part by weight of component (C).
本発明の外用組成物における(C)成分の含有量については、外用組成物の形態等に応じて適宜設定されるが、例えば０．５～１０重量％、好ましくは１～１０重量％、更に好ましくは１～５重量％が挙げられる。また、本発明の外用組成物において、(A)成分に対する(C)成分の比率については、これらの成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(C)成分が０．２５～２００重量部、好ましくは０．６～１００重量部、更に好ましくは０．６～５０重量部が挙げられる。 The content of component (C) in the topical composition of the present invention is appropriately set depending on the form of the topical composition, and may be, for example, 0.5 to 10% by weight, preferably 1 to 10% by weight, and more preferably 1 to 5% by weight. In addition, the ratio of component (C) to component (A) in the topical composition of the present invention is determined depending on the content of each of these components, and may be, for example, 0.25 to 200 parts by weight, preferably 0.6 to 100 parts by weight, and more preferably 0.6 to 50 parts by weight of component (C) per part by weight of component (A).
本発明の外用組成物における(D)成分の含有量については、外用組成物の形態等に応じて適宜設定されるが、例えば０．５～１０重量％、好ましくは１～１０重量％、更に好ましくは１～５重量％が挙げられる。また、本発明の外用組成物において、(A)成分に対する(D)成分の比率については、これらの成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(D)成分が０．２５～２００重量部、好ましくは０．６～１００重量部、更に好ましくは０．６～５０重量部が挙げられる。 The content of component (D) in the topical composition of the present invention is appropriately set depending on the form of the topical composition, and may be, for example, 0.5 to 10% by weight, preferably 1 to 10% by weight, and more preferably 1 to 5% by weight. In addition, the ratio of component (D) to component (A) in the topical composition of the present invention is determined depending on the content of each of these components, and may be, for example, 0.25 to 200 parts by weight, preferably 0.6 to 100 parts by weight, and more preferably 0.6 to 50 parts by weight of component (D) per part by weight of component (A).
［水］
本発明の外用組成物は、基剤等として水が含まれていてもよい。アラントイン又はその誘導体、並びに尿素と共に、水を含む外用組成物では、保存によりアラントイン及び／又はその誘導体の分解が顕著になる傾向があるが、本発明の外用組成物では、基剤等として水が含まれていても、アラントイン及び／又はその誘導体の分解を効果的に抑制することができる。
[water]
The topical composition of the present invention may contain water as a base, etc. In a topical composition containing allantoin or a derivative thereof, urea, and water, the decomposition of allantoin and/or its derivatives tends to become significant during storage, but the topical composition of the present invention can effectively suppress the decomposition of allantoin and/or its derivatives even if it contains water as a base, etc.
本発明の外用組成物において、水を含有させる場合、その含有量については、外用組成物の形態等に応じて適宜設定されるが、例えば２５～９７．９５重量％、好ましくは３０～９０重量％、更に好ましくは３５～８５重量％が挙げられる。 When the topical composition of the present invention contains water, the content of water is appropriately set depending on the form of the topical composition, and may be, for example, 25 to 97.95% by weight, preferably 30 to 90% by weight, and more preferably 35 to 85% by weight.
［多価アルコール］
本発明の外用組成物は、保湿作用の増強等を目的として、必要に応じて、多価アルコールが含まれていてもよい。
[Polyhydric alcohol]
The topical composition of the present invention may contain a polyhydric alcohol, if necessary, for the purpose of enhancing the moisturizing effect.
多価アルコールとしては、薬学的又は香粧学的に許容されることを限度として特に制限されないが、例えば、１，３－ブチレングリコール、エチレングリコール、プロピレングリコール、イソプレングリコール、ジエチレングリコール、ジプロピレングリコール、グリセリン等が挙げられる。これらの多価アルコールの中でも、好ましくはプロピレングリコール、グリセリンが挙げられる。これらの多価アルコールは、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The polyhydric alcohol is not particularly limited as long as it is pharma- ceutically or cosmetically acceptable, but examples include 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, glycerin, and the like. Among these polyhydric alcohols, propylene glycol and glycerin are preferred. These polyhydric alcohols may be used alone or in combination of two or more.
本発明の外用組成物において、多価アルコールを含有させる場合、その含有量については、使用する多価アルコールの種類、外用組成物の形態等に応じて適宜設定すればよいが、例えば１～２０重量％、好ましくは１．５～１５重量％、更に好ましくは２～１０重量％が挙げられる。 When the topical composition of the present invention contains a polyhydric alcohol, its content may be appropriately set depending on the type of polyhydric alcohol used, the form of the topical composition, etc., but may be, for example, 1 to 20% by weight, preferably 1.5 to 15% by weight, and more preferably 2 to 10% by weight.
［増粘剤］
本発明の外用組成物は、前述する成分の他に、粘性の調節等のために、必要に応じて、増粘剤が含まれていてもよい。
[Thickener]
In addition to the components described above, the topical composition of the present invention may contain a thickener, if necessary, for adjusting the viscosity, etc.
増粘剤としては、薬学的又は香粧学的に許容されることを限度として特に制限されないが、例えば、キサンタンガム、グアーガム、ローカストビーンガム、カラギーナン、デキストラン、メチルセルロース、エチルセルロース、カルボキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、アルギン酸ナトリウム、アルギン酸プロピレングリコールエステル、ポリビニルアルコール、ポリビニルピロリドン、ポリビニルメチルエーテル、カルボキシビニルポリマー、アクリル酸メタクリル酸アルキル共重合体、ポリアクリル酸ナトリウムベントナイト、デキストリン脂肪酸エステル、ペクチン等が挙げられる。これらの増粘剤の中でも、好ましくはカルボキシビニルポリマーが挙げられる。これらの増粘剤は１種又は２種以上を組み合わせて使用できる。 Thickeners are not particularly limited as long as they are pharma- ceutically or cosmetically acceptable, but examples include xanthan gum, guar gum, locust bean gum, carrageenan, dextran, methylcellulose, ethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, sodium alginate, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether, carboxyvinyl polymer, acrylic acid alkyl methacrylate copolymer, sodium polyacrylate bentonite, dextrin fatty acid ester, pectin, and the like. Among these thickeners, carboxyvinyl polymer is preferred. These thickeners can be used alone or in combination of two or more.
本発明の外用組成物において、増粘剤を含有させる場合、その含有量については、使用する増粘剤の種類、付与すべき粘性、外用組成物の形態等に応じて適宜設定すればよいが、例えば０．０１～１．５重量％、好ましくは０．０５～１重量％、更に好ましくは０．１～１．０重量％が挙げられる。 When a thickener is contained in the topical composition of the present invention, the content may be appropriately set depending on the type of thickener used, the viscosity to be imparted, the form of the topical composition, etc., and may be, for example, 0.01 to 1.5% by weight, preferably 0.05 to 1% by weight, and more preferably 0.1 to 1.0% by weight.
［キレート剤］
本発明の外用組成物には、前述する成分の他に、必要に応じて、キレート剤を含んでいてもよい。
[Chelating Agent]
The topical composition of the present invention may contain a chelating agent, if necessary, in addition to the components described above.
キレート剤としては、薬学的又は香粧学的に許容されることを限度として特に制限されないが、例えば、エデト酸、クエン酸、コハク酸、及びこれら塩等が挙げられる。塩の形態としては、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩等が挙げられる。これらのキレート剤の中でも、好ましくはエデト酸及びその塩、より好ましくはエデト酸ナトリウムが挙げられる。これらのキレート剤は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The chelating agent is not particularly limited as long as it is pharma- ceutically or cosmetically acceptable, but examples thereof include edetic acid, citric acid, succinic acid, and salts thereof. Examples of salt forms include alkali metal salts such as sodium salts and potassium salts. Among these chelating agents, edetic acid and its salts are preferred, and sodium edetate is more preferred. These chelating agents may be used alone or in combination of two or more.
本発明の外用組成物にキレート剤を含有させる場合、その含有量については、使用するキレート剤の種類、外用組成物の形態等に応じて適宜設定すればよいが、例えば０．０１～２重量％、好ましくは０．０１～１重量％、更に好ましくは０．０２～０．５重量％が挙げられる。 When a chelating agent is contained in the topical composition of the present invention, the content may be appropriately set depending on the type of chelating agent used, the form of the topical composition, etc., but may be, for example, 0.01 to 2% by weight, preferably 0.01 to 1% by weight, and more preferably 0.02 to 0.5% by weight.
［その他の成分］
本発明の外用組成物は、前述する成分の他に、必要に応じて、通常使用される他の添加剤が含まれていてもよい。このような添加剤としては、例えば、界面活性剤、１価低級アルコール、植物油、動物油、鉱物油、脂肪酸アルキルエステル、脂肪酸、高級アルコール、ｐＨ調節剤、緩衝剤、可溶化剤、防腐剤、保存剤、酸化防止剤、安定化剤、香料、着色料等が挙げられる。本発明の外用組成物において、これらの添加剤を含有させる場合、その含有量については、使用する添加剤の種類等に応じて適宜設定すればよい。
[Other ingredients]
In addition to the above-mentioned components, the composition for external use of the present invention may contain other additives that are commonly used as necessary.Such additives include, for example, surfactants, monohydric lower alcohols, vegetable oils, animal oils, mineral oils, fatty acid alkyl esters, fatty acids, higher alcohols, pH regulators, buffers, solubilizers, preservatives, preservatives, antioxidants, stabilizers, fragrances, colorants, etc.When these additives are contained in the composition for external use of the present invention, the content of these additives may be appropriately set according to the type of additives used, etc.
本発明の外用組成物は、前述する成分の他に、薬理成分が含まれていてもよい。このような薬理成分としては、例えば、ステロイド剤、抗ヒスタミン剤、局所麻酔剤、アラントイン及びその誘導体以外の抗炎症剤、尿素以外の保湿剤、殺菌剤、抗菌剤、鎮痒剤、皮膚保護剤、血行促進成分、ビタミン類、ムコ多糖類等が挙げられる。これらの薬理成分は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、本発明の外用組成物において、これらの薬理成分を含有させる場合、その濃度については、使用する薬理成分の種類、期待する効果等に応じて適宜設定すればよい。 The topical composition of the present invention may contain pharmacological ingredients in addition to the ingredients described above. Examples of such pharmacological ingredients include steroids, antihistamines, local anesthetics, anti-inflammatory agents other than allantoin and its derivatives, moisturizers other than urea, bactericides, antibacterial agents, antipruritic agents, skin protective agents, blood circulation promoting ingredients, vitamins, mucopolysaccharides, and the like. These pharmacological ingredients may be used alone or in combination of two or more. When these pharmacological ingredients are contained in the topical composition of the present invention, the concentration of the pharmacological ingredients may be appropriately set depending on the type of pharmacological ingredient used, the expected effect, and the like.
［ｐＨ］
本発明の外用組成物のｐＨとしては、アラントイン及び／又はその誘導体が安定に保持される範囲であればよいが、例えば２～９、好ましくは３～８、更に好ましくは４～７．５、調整直後であれば２～５．５が挙げられる。
[pH]
The pH of the topical composition of the present invention may be within a range in which allantoin and/or its derivatives are stably maintained, for example, 2 to 9, preferably 3 to 8, more preferably 4 to 7.5, and immediately after adjustment, 2 to 5.5.
［剤型・製剤形態］
本発明の外用組成物の剤型については、経皮適用可能であることを限度として特に制限されず、液状、半固形状（クリーム状、ゲル状、軟膏状、ペースト状）、固形状等のいずれであってもよいが、好ましくは液状又は半固形状が挙げられる。また、本発明の外用組成物は、水中油型乳化製剤、油中水型乳化製剤等の乳化製剤であってもよく、また可溶化型製剤、水性軟膏等の非乳化製剤であってもよい。
[Dosage form/formulation]
The dosage form of the topical composition of the present invention is not particularly limited as long as it is applicable transdermally, and may be any of liquid, semi-solid (cream, gel, ointment, paste), solid, etc., but is preferably liquid or semi-solid. The topical composition of the present invention may be an emulsion preparation such as an oil-in-water emulsion preparation or a water-in-oil emulsion preparation, or may be a non-emulsion preparation such as a solubilized preparation or an aqueous ointment.
また、本発明の外用組成物は、皮膚に適用されるものである限り、皮膚外用医薬品（医薬部外品を含む）、化粧料、皮膚洗浄料等のいずれの製剤形態であってもよい。 In addition, the topical composition of the present invention may be in any formulation, such as a topical drug for skin (including quasi-drugs), a cosmetic, or a skin cleanser, so long as it is applied to the skin.
本発明の外用組成物の製剤形態として、具体的には、クリーム剤、ローション剤、ジェル剤、乳液剤、液剤、パップ剤、貼付剤、リニメント剤、エアゾール剤、水性軟膏剤、パック剤等の皮膚外用医薬品；水性軟膏、クリーム、乳液、化粧水、ローション、パック、ゲル等の化粧料；ボディーシャンプー、ヘアシャンプー、リンス等の皮膚洗浄料等が挙げられる。これらの中でも、好ましくは皮膚外用医薬品が挙げられる。 Specific examples of the formulation of the topical composition of the present invention include topical skin medicines such as creams, lotions, gels, emulsions, liquids, poultices, patches, liniments, aerosols, aqueous ointments, and packs; cosmetics such as aqueous ointments, creams, emulsions, lotions, packs, and gels; and skin cleansers such as body shampoos, hair shampoos, and rinses. Of these, topical skin medicines are preferred.
本発明の外用組成物は、(A)成分に基づいて、組織修復賦活作用、抗炎症作用、鎮痒作用等を発揮でき、更に含有する(B)成分に基づいて、保湿作用、細胞賦活作用、抗菌作用、鎮痒作用等を発揮できるので、保湿、肌荒れ改善、乾燥性皮膚疾患、炎症性皮膚疾患、肥厚性瘢痕、ケロイド等の予防又は治療等の目的で好適に使用される。 The topical composition of the present invention can exert tissue repair activation, anti-inflammatory, and antipruritic effects based on the component (A), and can also exert moisturizing, cell activation, antibacterial, and antipruritic effects based on the component (B), making it suitable for use in moisturizing, improving rough skin, and preventing or treating dry skin diseases, inflammatory skin diseases, hypertrophic scars, keloids, and the like.
２．アラントイン及び／又はその誘導体の安定化方法
本発明は、更に、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物におけるアラントイン及び／又はその誘導体の安定化方法であって、外用組成物中に、(A)アラントイン及び／又はその誘導体、並びに(B)尿素と共に、(C)グリシン、及び(D)アラニンを配合することを特徴とする、安定化方法を提供する。
2. Method for stabilizing allantoin and/or its derivatives The present invention further provides a method for stabilizing allantoin and/or its derivatives in a composition for external use containing allantoin and/or its derivatives, and urea, which is characterized by blending (A) allantoin and/or its derivatives, and (B) urea, together with (C) glycine, and (D) alanine, in the composition for external use.
本発明の安定化方法において、使用する(A)～(D)の種類や配合量、配合される他の成分の種類や含有量、外用組成物の製剤形態等については、前記「１．外用組成物」の場合と同様である。 In the stabilization method of the present invention, the types and amounts of (A) to (D) used, the types and contents of other ingredients to be added, the formulation form of the topical composition, etc. are the same as those in "1. Topical composition" above.
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 The present invention will be explained in more detail below with reference to examples, but the present invention is not limited to these.
試験例１
表１に示す成分を配合して外用組成物（液剤）を調製した。得られた外用組成物を、遮光条件下で、５０℃で２週間、又は５０℃で１カ月間保存した。製造直後と保存後の外用組成物について、ｐＨ及びアラントイン含量を測定した。ｐＨの測定はｐＨメーター（「ＨＯＲＩＢＡ」、株式会社堀場製作所）を用いて行った。アラントイン含量は高速液体クロマトグラフィーにて測定した。測定されたアラントイン含量の値から、アラントイン含有率（仕込み量を１００％とした場合の相対値）（％）を算出した。
Test Example 1
The components shown in Table 1 were mixed to prepare a topical composition (liquid). The obtained topical composition was stored under light-shielded conditions at 50°C for 2 weeks or at 50°C for 1 month. The pH and allantoin content of the topical composition immediately after production and after storage were measured. The pH was measured using a pH meter ("HORIBA", Horiba Ltd.). The allantoin content was measured by high performance liquid chromatography. The allantoin content (relative value when the amount charged is taken as 100%) (%) was calculated from the measured allantoin content.
得られた結果を表１に示す。アラントイン及び尿素を含む場合（比較例１及び２）には、保存によりｐＨの向上とアラントイン残存率の低下が著しかった。また、アラントイン及び尿素に加えてグリシンを含む場合（比較例３及び４）には、比較例１及び２に比べて、保存後のｐＨの上昇が抑えられ、アラントイン残存率の向上が認められた。これに対して、アラントイン及び尿素に加えてグリシン及びアラニンを含む場合（実施例１）には、保存後のｐＨは比較例４と同程度であったものの、比較例４に比べてアラントイン残存率は格段に高くなっていた。 The results are shown in Table 1. When allantoin and urea were included (Comparative Examples 1 and 2), the pH increased significantly and the allantoin residual rate decreased significantly upon storage. When glycine was included in addition to allantoin and urea (Comparative Examples 3 and 4), the increase in pH after storage was suppressed and the allantoin residual rate was improved compared to Comparative Examples 1 and 2. In contrast, when glycine and alanine were included in addition to allantoin and urea (Example 1), the pH after storage was similar to that of Comparative Example 4, but the allantoin residual rate was significantly higher than that of Comparative Example 4.
処方例
表２及び３に示す組成の外用組成物（処方例１～６はゲル剤、処方例７は液剤、処方例８は水中油型乳化製剤）を調製した。得られた外用組成物を前記試験例１と同様の方法で保存安定性を評価したところ、いずれも保存後のアラントイン残存率が高く、優れた保存安定性を有していた。
External compositions having the compositions shown in Formulation Examples 2 and 3 (Formulation Examples 1 to 6 are gels, Formulation Example 7 is a liquid, and Formulation Example 8 is an oil-in-water emulsion preparation) were prepared. The storage stability of the obtained external compositions was evaluated in the same manner as in Test Example 1, and all of them had a high residual rate of allantoin after storage and excellent storage stability.
Claims (3)
（但し、下記(i)～(iii)に示すいずれかの成分を含む場合を除く：
(i)下記一般式（１）に表される化合物、その立体異性体及び／又はそれらの薬理学的に許容される塩
(ii)Ｄ－パントテニルアルコール
(iii)プレドニゾロン吉草酸エステル酢酸エステル、ヒドロコルチゾン酪酸エステル、又はベタメタゾン吉草酸エステル）。 A composition for external use comprising: (A) at least one selected from the group consisting of allantoin, aluminum chlorhydrate, aluminum hydroxyl, aluminum hydroxyl, aluminum dihydroxyl, and aluminum chlorhydrate; (B) 5 to 20% by weight of urea; (C) glycine; and (D) alanine (excluding the case where any of the following components (i) to (iii) is contained:
(i) A compound represented by the following general formula (1), its stereoisomer , and/or a pharmacologically acceptable salt thereof:
(ii) D-Pantothenyl alcohol
(iii) prednisolone valerate acetate, hydrocortisone butyrate, or betamethasone valerate).
The composition for external use according to claim 1 or 2, further comprising water.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001114688A (en) | 1999-10-15 | 2001-04-24 | Tamuto Keshohin Kk | Skin lotion |
| JP2014111563A (en) | 2012-10-31 | 2014-06-19 | Rohto Pharmaceut Co Ltd | External composition for skin |
| JP2019014709A (en) | 2017-07-07 | 2019-01-31 | ポーラ化成工業株式会社 | Skin care composition |
| JP2019019077A (en) | 2017-07-18 | 2019-02-07 | ポーラ化成工業株式会社 | Skin external composition |
| WO2020251017A1 (en) | 2019-06-14 | 2020-12-17 | ゼリア新薬工業株式会社 | Composition for external application |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6030646B2 (en) * | 1974-10-22 | 1985-07-17 | 興和株式会社 | Method for stabilizing skin treatment compositions |
| JPS52109487A (en) * | 1976-03-10 | 1977-09-13 | Sunstar Inc | Hydrated composites stably compounded with urea |
| JPS56156211A (en) * | 1980-05-07 | 1981-12-02 | Teika Seiyaku Kk | Preparation of stable allantoin pharmaceutical |
| JPS63159317A (en) * | 1986-12-24 | 1988-07-02 | Terumo Corp | Allantoin-containing aqueous preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001114688A (en) | 1999-10-15 | 2001-04-24 | Tamuto Keshohin Kk | Skin lotion |
| JP2014111563A (en) | 2012-10-31 | 2014-06-19 | Rohto Pharmaceut Co Ltd | External composition for skin |
| JP2014133733A (en) | 2012-10-31 | 2014-07-24 | Rohto Pharmaceut Co Ltd | External composition for skin |
| JP2019014709A (en) | 2017-07-07 | 2019-01-31 | ポーラ化成工業株式会社 | Skin care composition |
| JP2019019077A (en) | 2017-07-18 | 2019-02-07 | ポーラ化成工業株式会社 | Skin external composition |
| WO2020251017A1 (en) | 2019-06-14 | 2020-12-17 | ゼリア新薬工業株式会社 | Composition for external application |
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