JP5689242B2 - Emulsified composition and external preparation for skin containing the same - Google Patents
Emulsified composition and external preparation for skin containing the same Download PDFInfo
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- JP5689242B2 JP5689242B2 JP2010054010A JP2010054010A JP5689242B2 JP 5689242 B2 JP5689242 B2 JP 5689242B2 JP 2010054010 A JP2010054010 A JP 2010054010A JP 2010054010 A JP2010054010 A JP 2010054010A JP 5689242 B2 JP5689242 B2 JP 5689242B2
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- glycyrrhetinic acid
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- 239000000203 mixture Substances 0.000 title claims description 50
- 238000002360 preparation method Methods 0.000 title claims description 15
- 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 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000000839 emulsion Substances 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 10
- 238000013329 compounding Methods 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- SYELZBGXAIXKHU-UHFFFAOYSA-N dodecyldimethylamine N-oxide Chemical compound CCCCCCCCCCCC[N+](C)(C)[O-] SYELZBGXAIXKHU-UHFFFAOYSA-N 0.000 description 13
- 239000008213 purified water Substances 0.000 description 13
- 238000004945 emulsification Methods 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 8
- -1 alkyl dimethylamine oxide Chemical compound 0.000 description 7
- ONHFWHCMZAJCFB-UHFFFAOYSA-N myristamine oxide Chemical compound CCCCCCCCCCCCCC[N+](C)(C)[O-] ONHFWHCMZAJCFB-UHFFFAOYSA-N 0.000 description 7
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000002537 cosmetic Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 239000004359 castor oil Substances 0.000 description 4
- 235000019438 castor oil Nutrition 0.000 description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 3
- IBOBFGGLRNWLIL-UHFFFAOYSA-N n,n-dimethylhexadecan-1-amine oxide Chemical compound CCCCCCCCCCCCCCCC[N+](C)(C)[O-] IBOBFGGLRNWLIL-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 229940058015 1,3-butylene glycol Drugs 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
- 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 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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920002385 Sodium hyaluronate Polymers 0.000 description 2
- 235000019437 butane-1,3-diol Nutrition 0.000 description 2
- 239000006071 cream Substances 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
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000693 micelle Substances 0.000 description 2
- 239000002304 perfume Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229940010747 sodium hyaluronate Drugs 0.000 description 2
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical compound [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 2
- 229940042585 tocopherol acetate Drugs 0.000 description 2
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 240000004670 Glycyrrhiza echinata Species 0.000 description 1
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 description 1
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 description 1
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 1
- 241000282320 Panthera leo Species 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 239000013065 commercial product Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 239000001685 glycyrrhizic acid Substances 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940010454 licorice Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- ONLRKTIYOMZEJM-UHFFFAOYSA-N n-methylmethanamine oxide Chemical compound C[NH+](C)[O-] ONLRKTIYOMZEJM-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Landscapes
- Cosmetics (AREA)
Description
本発明は、水や石油エーテルなどに不溶なβ−グリチルレチン酸を安定に含有させた乳化組成物およびこれを含有する皮膚外用剤に関する。 The present invention relates to an emulsified composition stably containing β-glycyrrhetinic acid insoluble in water, petroleum ether and the like, and a skin external preparation containing the same.
アルキルジメチルアミンオキシドはカチオン性を有する界面活性剤であり、洗浄剤の増泡剤や皮膚刺激緩和剤など、洗浄を目的とした製剤に使われている（非特許文献１）。さらに、経皮吸収促進剤としての効果があることも知られている（特許文献１） Alkyldimethylamine oxide is a surfactant having a cationic property and is used in preparations intended for cleaning, such as a foaming agent for a cleaning agent and a skin irritation mitigating agent (Non-patent Document 1). Furthermore, it is also known to have an effect as a transdermal absorption enhancer (Patent Document 1).
アルキルジメチルアミンオキシド水溶液は、塩化ナトリウムを添加することによって系全体の粘性を上げ、ひも状ミセルを形成することが知られている（非特許文献２）。また、桂皮酸を添加することによってひも状ミセルやベシクルを形成することも知られている（非特許文献３）。アルキルジメチルアミンオキシドは、イオン性をもつ分子と相互作用することが古くから知られており、アニオン性界面活性剤と相互作用し、シャンプーなどの洗浄剤の増粘、増泡効果にも役立つ（非特許文献１）。しかしながら、β−グリチルレチン酸を溶解させるために、アルキルジメチルアミンオキシドを配合させて用いることは開示されていない。 It is known that an aqueous solution of alkyldimethylamine oxide increases the viscosity of the whole system by adding sodium chloride, and forms string micelles (Non-patent Document 2). It is also known to form string micelles and vesicles by adding cinnamic acid (Non-patent Document 3). Alkyldimethylamine oxide has long been known to interact with ionic molecules, interacts with anionic surfactants, and is useful for thickening and foaming effects in detergents such as shampoos ( Non-patent document 1). However, there is no disclosure that alkyldimethylamine oxide is used in combination to dissolve β-glycyrrhetinic acid.
一方、β−グリチルレチン酸は急性や慢性の皮膚炎に対し著しい効果があるといわれており、多用薬としての臨床報告も国内外で多くみられる。化学構造が類似しているコルチゾン（副腎皮質ホルモン）に比べて作用は緩和であるため、化粧品では古くから使われている（非特許文献４）。また、抗炎症、抗アレルギー、細菌発育阻止、５α−リダクターゼ活性阻害などの作用により、育毛効果があることも知られている（非特許文献５）。β−グリチルレチン酸は高級アルコールやエタノールには溶解することが知られている。しかし、水や石油エーテルなどには不溶のため、製剤上の制約があり配合には制限があった。β−グリチルレチン酸を高級アルコールやエタノールに溶解させて界面活性剤で乳化あるいは可溶化させる方法があるがいずれも経時的に析出する。 On the other hand, β-glycyrrhetinic acid is said to have a remarkable effect on acute and chronic dermatitis, and many clinical reports as multi-drugs are also seen in Japan and overseas. Compared to cortisone (adrenocortical hormone) that has a similar chemical structure, its action is milder, so it has been used in cosmetics for a long time (Non-patent Document 4). It is also known that there is a hair-growth effect due to anti-inflammation, anti-allergy, bacterial growth inhibition, 5α-reductase activity inhibition and the like (Non-patent Document 5). It is known that β-glycyrrhetinic acid is soluble in higher alcohols and ethanol. However, since it is insoluble in water, petroleum ether, etc., there are restrictions on the formulation and there are restrictions on the formulation. There are methods in which β-glycyrrhetinic acid is dissolved in a higher alcohol or ethanol and emulsified or solubilized with a surfactant.
従って、保存安定性に優れたβ−グリチルレチン酸を含有する乳化組成物が望まれている。 Therefore, an emulsion composition containing β-glycyrrhetinic acid having excellent storage stability is desired.
本発明者らは、これらの解決課題に対し検討した結果、アルキルジメチルアミンオキシドを配合することによりβ−グリチルレチン酸を可溶化あるいは乳化させた乳化組成物が保存安定性に優れることを見出した。すなわち、本発明は、化学式１で表されるアルキルジメチルアミンオキシド、β−グリチルレチン酸および水を配合した乳化組成物としている。 As a result of studying these problems, the present inventors have found that an emulsion composition in which β-glycyrrhetinic acid is solubilized or emulsified by blending alkyldimethylamine oxide is excellent in storage stability. That is, the present invention is an emulsified composition in which alkyldimethylamine oxide represented by Chemical Formula 1, β-glycyrrhetinic acid and water are blended.
本発明に用いられる化学式１（Ｒはアルキル基）で表されるアルキルジメチルアミンオキシドは、Ｒがラウリル基あるいはミリスチル基から選ばれる。本発明の乳化組成物を皮膚外用剤に使用する場合には、ラウリルジメチルアミンオキシドの市販品として、ソフタミン Ｌ（東邦化学（株）製、商品名）、アロモックスＤＭ１２Ｄ−Ｗ（Ｃ）（ライオン（株）製、商品名）、ユニセーフＡ−ＬＭＲ（日油（株）製、商品名）等、ミリスチルジメチルアミンオキシドの市販品として、アロモックスＤＭ１４Ｄ−Ｎ（ライオン（株）製、商品名）、ユニセーフＡ−ＭＭ（日油（株）製、商品名）等が挙げられる。また、混合品として、ＢＡＬＯＸ１２（ラウリルジメチルアミンオキシド６７％、ミリスチルジメチルアミンオキシド２５％、セチルジメチルアミンオキシド８％：ロンザジャパン（株）製、商品名）、ＢＡＬＯＸ１４（ラウリルジメチルアミンオキシド３８％、ミリスチルジメチルアミンオキシド５２％、セチルジメチルアミンオキシド１０％：ロンザジャパン（株）製、商品名）等がある。 In the alkyldimethylamine oxide represented by the chemical formula 1 (R is an alkyl group) used in the present invention, R is selected from a lauryl group or a myristyl group. When the emulsified composition of the present invention is used as a skin external preparation, commercially available products of lauryl dimethylamine oxide include Softam L (trade name, manufactured by Toho Chemical Co., Ltd.), Aromox DM12D-W (C) (Lion ( As a commercial product of myristyldimethylamine oxide, such as Unisafe A-LMR (trade name, manufactured by NOF Corporation), Unisafe A-LMR (trade name), Unisafe A-LMR (trade name), Unisafe A-MM (made by NOF Corporation, a brand name) etc. are mentioned. Also, as a mixed product, BALOX 12 (67% lauryl dimethylamine oxide, 25% myristyl dimethylamine oxide, 8% cetyl dimethylamine oxide: Lonza Japan Co., Ltd., trade name), BALOX 14 (38% lauryl dimethylamine oxide, myristyl) Dimethylamine oxide 52%, cetyldimethylamine oxide 10%: Lonza Japan Co., Ltd., trade name) and the like.
乳化組成物を構成するアルキルジメチルアミンオキシドの配合量は１〜１０重量％程度が望ましく、特に５〜１０重量％が望ましい。配合量が１重量％よりも低い場合は沈殿が生じることがある。１０重量％を超えると系全体の粘度が上昇し、撹拌効率が悪くなることがある。 The amount of alkyldimethylamine oxide constituting the emulsified composition is preferably about 1 to 10% by weight, particularly 5 to 10% by weight. If the amount is less than 1% by weight, precipitation may occur. If it exceeds 10% by weight, the viscosity of the whole system increases, and the stirring efficiency may deteriorate.
β−グリチルレチン酸は日本薬局方外医薬品規格や医薬部外品原料規格２００６に収載されている。本発明で用いるβ−グリチルレチン酸は、甘草から得られるグリチルリチン酸の加水分解によって得られるものが挙げられる。本発明の乳化組成物を皮膚外用剤に使用する場合には、市販品として、β−グリチルレチン酸（丸善製薬（株）製、商品名）、ＮＩＫＫＯＬ グリチルレチン酸（日光ケミカルズ（株）製、商品名）等が挙げられる。 β-glycyrrhetinic acid is listed in the Japanese Pharmacopoeia Pharmaceutical Standards and Quasi-drug Raw Material Standards 2006. Examples of the β-glycyrrhetinic acid used in the present invention include those obtained by hydrolysis of glycyrrhizic acid obtained from licorice. When the emulsion composition of the present invention is used as a skin external preparation, commercially available products include β-glycyrrhetinic acid (manufactured by Maruzen Pharmaceutical Co., Ltd., trade name), NIKKOL glycyrrhetinic acid (manufactured by Nikko Chemicals Co., Ltd., trade name). ) And the like.
また、β−グリチルレチン酸の配合量は、０．３〜３．５重量％程度が望ましく、特に１．０〜３．５重量％が望ましい。０．３重量％よりも低くなると皮膚外用剤に配合する際に製造効率が悪い場合もある。３．５重量％を超えると分離する場合がある。 Further, the amount of β-glycyrrhetinic acid is preferably about 0.3 to 3.5% by weight, and more preferably 1.0 to 3.5% by weight. If it is lower than 0.3% by weight, the production efficiency may be poor when blended into a skin external preparation. If it exceeds 3.5% by weight, it may be separated.
次に本発明の乳化組成物を製造するには、アルキルジメチルアミンオキシドを予め水に溶解させた後、β−グリチルレチン酸を添加し混合することにより得られる。 Next, the emulsion composition of the present invention can be obtained by previously dissolving alkyldimethylamine oxide in water and then adding and mixing β-glycyrrhetinic acid.
その一例を具体的に説明すると、アルキルジメチルアミンオキシドを水に溶解し、β−グリチルレチン酸を加えおよそ６０℃に加温しながら、ホモミキサーで乳化する。乳化後は３０℃まで冷却し、乳化組成物を得ることができる。なお、微生物等の汚染を考慮し、防腐剤やｐＨ調整剤等の溶質を添加してもよい。 An example of this is specifically described. Alkyldimethylamine oxide is dissolved in water, and β-glycyrrhetinic acid is added and emulsified with a homomixer while heating to about 60 ° C. After emulsification, it can be cooled to 30 ° C. to obtain an emulsified composition. In consideration of contamination by microorganisms, solutes such as preservatives and pH adjusters may be added.
また、本発明の乳化組成物は、使用時に水性の製剤（精製水、あるいは化粧水、美容液、ジェル、乳液、クリーム等の製剤）に配合して使用する皮膚外用剤とすることができる。使用時に水性の製剤（精製水、あるいは化粧水、美容液、ジェル、乳液、クリーム等の製剤）に配合する場合には、乳化組成物として必ずしも必要ではないが、β−グリチルレチン酸の経時的な析出を防ぐために非イオン性界面活性剤を配合してもよい。他に、化粧品に配合される油性基剤、脂肪酸、アルコール、水性基剤、酸化防止剤、防腐剤、金属イオン封鎖剤、ｐＨ調製剤、水溶性ポリマー、シリコーン油、紫外線吸収剤、ビタミン類、アミノ酸類、糖類などを配合してもよい。 Moreover, the emulsified composition of the present invention can be used as a skin external preparation to be used by blending with an aqueous preparation (preparation of purified water or lotion, cosmetic liquid, gel, milky lotion, cream, etc.) at the time of use. When blended into aqueous preparations (preparations of purified water or lotion, cosmetic liquid, gel, milky lotion, cream, etc.) at the time of use, it is not always necessary as an emulsified composition, but β-glycyrrhetinic acid over time In order to prevent precipitation, a nonionic surfactant may be added. Besides, oily base, fatty acid, alcohol, aqueous base, antioxidant, preservative, sequestering agent, pH adjuster, water-soluble polymer, silicone oil, UV absorber, vitamins, Amino acids, sugars and the like may be blended.
次に実施例、比較例及び試験例を挙げて本発明をさらに詳細に説明する。 Next, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples.
乳化組成物の調製
ラウリルジメチルアミンオキシド３０重量％水溶液（ソフタミン Ｌ）３．３ｇ（ラウリルジメチルアミンオキシド ０．９９ｇ）にβ−グリチルレチン酸０．３ｇ及び精製水９６．４ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。
Preparation of emulsion composition To 3.3 g of lauryl dimethylamine oxide 30% by weight aqueous solution (Softamin L) (0.99 g of lauryl dimethylamine oxide) was added 0.3 g of β-glycyrrhetinic acid and 96.4 g of purified water, and the mixture was heated to 60 ° C. After warming, the mixture was emulsified with a homomixer manufactured by Silverson at 8,000 rpm for 5 minutes. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
ラウリルジメチルアミンオキシド３０重量％水溶液（ソフタミン Ｌ）１６．７ｇ（ラウリルジメチルアミンオキシド ５．０１ｇ）にβ−グリチルレチン酸１．７５ｇ及び精製水８１．５５ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。 After adding 1.75 g of β-glycyrrhetinic acid and 81.55 g of purified water to 16.7 g of lauryl dimethylamine oxide 30% by weight aqueous solution (Softamin L) (5.01 g of lauryl dimethylamine oxide), the mixture was heated to 60 ° C. and then silver. The mixture was emulsified at 8,000 rpm for 5 minutes with a Son homomixer. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
ラウリルジメチルアミンオキシド３０重量％水溶液（ソフタミン Ｌ）３３．３ｇ（ラウリルジメチルアミンオキシド ９．９９ｇ）にβ−グリチルレチン酸３．５ｇ及び精製水６３．２ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。 After adding 3.5 g of β-glycyrrhetinic acid and 63.2 g of purified water to 33.3 g of lauryldimethylamine oxide 30% by weight aqueous solution (Softamin L) (9.99 g of lauryl dimethylamine oxide), the mixture was heated to 60 ° C., and then silver. The mixture was emulsified at 8,000 rpm for 5 minutes with a Son homomixer. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
ミリスチルジメチルアミンオキシド２５重量％水溶液（アロモックスＤＭ１４Ｄ−Ｎ）２０ｇ（ミリスチルジメチルアミンオキシド ５ｇ）にβ−グリチルレチン酸１．２５ｇ及び精製水７８．７５ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。 After adding 1.25 g of β-glycyrrhetinic acid and 78.75 g of purified water to 20 g of myristyldimethylamine oxide 25% by weight aqueous solution (Alomox DM14D-N) (5 g of myristyldimethylamine oxide), and heating to 60 ° C., Silverson The mixture was emulsified with a homomixer manufactured at 8,000 rpm for 5 minutes. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
ミリスチルジメチルアミンオキシド２５重量％水溶液（アロモックスＤＭ１４Ｄ−Ｎ）４０ｇ（ミリスチルジメチルアミンオキシド １０ｇ）にβ−グリチルレチン酸２．５ｇ及び精製水５７．５ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。 After adding 2.5 g of β-glycyrrhetinic acid and 57.5 g of purified water to 40 g of myristyl dimethylamine oxide 25% by weight aqueous solution (Aromox DM14D-N) (10 g of myristyl dimethylamine oxide) and heating to 60 ° C., Silverson The mixture was emulsified with a homomixer manufactured at 8,000 rpm for 5 minutes. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
混合アルキルジメチルアミンオキシド（ラウリルジメチルアミンオキシド３８％、ミリスチルジメチルアミンオキシド５２％、セチルジメチルアミンオキシド１０％）３０重量％水溶液（ＢＡＬＯＸ１４）３３．３ｇ（混合アルキルジメチルアミンオキシド ９．９９ｇ）にβ−グリチルレチン酸２．５ｇ及び精製水６４．２ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。 Mixed alkyldimethylamine oxide (lauryl dimethylamine oxide 38%, myristyl dimethylamine oxide 52%, cetyl dimethylamine oxide 10%) 30% by weight aqueous solution (BALOX 14) 33.3 g (mixed alkyl dimethylamine oxide 9.99 g) with β- After adding 2.5 g of glycyrrhetic acid and 64.2 g of purified water and heating to 60 ° C., the mixture was emulsified at 8,000 rpm for 5 minutes with a homomixer manufactured by Silverson. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
ラウリルジメチルアミンオキシド３０重量％水溶液（ソフタミン Ｌ）３３．３ｇ（ラウリルジメチルアミンオキシド ９．９９ｇ）にβ−グリチルレチン酸４．０ｇ及び精製水６２．７ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。 After adding 4.0 g of β-glycyrrhetinic acid and 62.7 g of purified water to 33.3 g of lauryl dimethylamine oxide 30% by weight aqueous solution (Softamin L) (9.99 g of lauryl dimethylamine oxide), the mixture was heated to 60 ° C. and then silver. The mixture was emulsified at 8,000 rpm for 5 minutes with a Son homomixer. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
（比較例１）
ポリオキシエチレン（９）ラウリルエーテル（平均付加モル数９：ＮＩＫＫＯＬ ＢＬ−９ＥＸ）５ｇにβ−グリチルレチン酸１．２５ｇ及び精製水９３．７５ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。
(Comparative Example 1)
After adding 1.25 g of β-glycyrrhetinic acid and 93.75 g of purified water to 5 g of polyoxyethylene (9) lauryl ether (average number of moles 9: NIKKOL BL-9EX), and heating to 60 ° C., manufactured by Silverson The mixture was emulsified with a homomixer at 8,000 rpm for 5 minutes. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
（比較例２）
ポリオキシエチレン（４０）硬化ヒマシ油（平均付加モル数４０：ＮＩＫＫＯＬ ＨＣＯ−４０）５ｇにβ−グリチルレチン酸１．２５ｇ及び精製水９３．７５ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。
(Comparative Example 2)
After adding 1.25 g of β-glycyrrhetinic acid and 93.75 g of purified water to 5 g of polyoxyethylene (40) hydrogenated castor oil (average number of moles 40: NIKKOL HCO-40), and heating to 60 ° C., Silverson The mixture was emulsified with a homomixer manufactured at 8,000 rpm for 5 minutes. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
（比較例３）
ポリオキシエチレン（６０）硬化ヒマシ油（平均付加モル数６０：ＮＩＫＫＯＬ ＨＣＯ−６０）５ｇにβ−グリチルレチン酸１．２５ｇ及び精製水９３．７５ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。
(Comparative Example 3)
After adding 1.25 g of β-glycyrrhetinic acid and 93.75 g of purified water to 5 g of polyoxyethylene (60) hydrogenated castor oil (average addition mole number 60: NIKKOL HCO-60), and heating to 60 ° C., Silverson The mixture was emulsified with a homomixer manufactured at 8,000 rpm for 5 minutes. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
（比較例４）
ポリオキシエチレン（３０）フィトステロール（平均付加モル数３０：ＮＩＫＫＯＬ ＢＰＳ−３０）５ｇにβ−グリチルレチン酸１．２５ｇ及び精製水９３．７５ｇを加え、６０℃まで加温した後、シルバーソン社製ホモミキサーにて８，０００ｒｐｍで５分間乳化した。乳化後、３０℃まで冷却し乳化組成物とした。
(Comparative Example 4)
After adding 1.25 g of β-glycyrrhetinic acid and 93.75 g of purified water to 5 g of polyoxyethylene (30) phytosterol (average addition mole number 30: NIKKOL BPS-30), and heating to 60 ° C. The mixture was emulsified for 5 minutes at 8,000 rpm. After emulsification, it was cooled to 30 ° C. to obtain an emulsified composition.
乳化組成物の保存安定性は、４０℃にて２週間静置後の状態を観察した。外観上、β−グリチルレチン酸が透明に溶解したものは◎、青白色に溶解したものは○、沈殿したものは×とした。 The storage stability of the emulsion composition was observed after standing at 40 ° C. for 2 weeks. In terms of appearance, β-glycyrrhetinic acid dissolved transparently was marked with “◎”, blue-white dissolved with “◯”, and precipitated with “x”.
乳化剤あるいは可溶化剤として使われる代表的な界面活性剤と比較すると、アルキルジメチルアミンオキシド（実施例１〜７）以外の界面活性剤（比較例１〜４）を使用したものすべて沈殿を生じた。また、実施例１〜７では沈殿はみられず保存安定性に優れていたが、実施例７でわずかな分離がみられた。ただし、４週間後でもその分離は変化がなく沈殿がみられなかったため製剤上問題ないと判断した。 Compared with representative surfactants used as emulsifiers or solubilizers, all of the surfactants other than alkyldimethylamine oxide (Examples 1 to 7) (Comparative Examples 1 to 4) were precipitated. . In Examples 1 to 7, precipitation was not observed and the storage stability was excellent, but in Example 7, slight separation was observed. However, even after 4 weeks, the separation did not change and precipitation was not observed, so it was judged that there was no problem in formulation.
次に、実施例３を配合した皮膚外用剤について示す。 Next, an external preparation for skin containing Example 3 will be described.
配合成分 配合量（重量％）
（１） ＥＤＴＡ−２Ｎａ ０．０５
（２） クエン酸 ０．０１
（３） １，３−ブチレングリコール ２．０
（４） グリセリン １．０
（５） ヒアルロン酸ナトリウム ０．０１
（６） ポリオキシエチレン（６０）硬化ヒマシ油 ０．１
（７） 香料 ０．０３
（８） 酢酸トコフェロール ０．００１
（９） エタノール ３．０
（１０）パラオキシ安息香酸メチル ０．１５
（１１）実施例３の乳化組成物 ５．０
（１２）水 残 量
合計 １００
Compounding ingredients Compounding amount (% by weight)
(1) EDTA-2Na 0.05
(2) Citric acid 0.01
(3) 1,3-butylene glycol 2.0
(4) Glycerin 1.0
(5) Sodium hyaluronate 0.01
(6) Polyoxyethylene (60) hydrogenated castor oil 0.1
(7) Perfume 0.03
(8) Tocopherol acetate 0.001
(9) Ethanol 3.0
(10) Methyl paraoxybenzoate 0.15
(11) Emulsion composition of Example 3 5.0
(12) Residual amount of water
Total 100
（比較例５）
配合成分 配合量（重量％）
（１） ＥＤＴＡ−２Ｎａ ０．０５
（２） クエン酸 ０．０１
（３） １，３−ブチレングリコール ２．０
（４） グリセリン １．０
（５） ヒアルロン酸ナトリウム ０．０１
（６） ポリオキシエチレン（６０）硬化ヒマシ油 ０．１
（７） 香料 ０．０３
（８） 酢酸トコフェロール ０．００１
（９） エタノール ３．０
（１０）β−グリチルレチン酸 ０．１７５
（１１）パラオキシ安息香酸メチル ０．１５
（１２）水 残 量
合計 １００
(Comparative Example 5)
Compounding ingredients Compounding amount (% by weight)
(1) EDTA-2Na 0.05
(2) Citric acid 0.01
(3) 1,3-butylene glycol 2.0
(4) Glycerin 1.0
(5) Sodium hyaluronate 0.01
(6) Polyoxyethylene (60) hydrogenated castor oil 0.1
(7) Perfume 0.03
(8) Tocopherol acetate 0.001
(9) Ethanol 3.0
(10) β-glycyrrhetinic acid 0.175
(11) Methyl paraoxybenzoate 0.15
(12) Residual amount of water
Total 100
上記実施例８の化粧水は透明な外観を有し、５℃、室温、４０℃における保存安定性はいずれも良好であった。比較例５は調製直後に白濁し、沈殿が生じた。 The lotion of Example 8 had a transparent appearance, and the storage stability at 5 ° C., room temperature, and 40 ° C. was all good. In Comparative Example 5, white turbidity occurred immediately after preparation, and precipitation occurred.
Claims (5)
化学式１（Ｒはアルキル基）で表されるアルキルジメチルアミンオキシドを予め水に溶解させた後、β−グリチルレチン酸を添加し混合することにより得られる乳化組成物であって、水の総量が８６．０〜９８．７重量％である乳化組成物。
An emulsion composition obtained by previously dissolving alkyldimethylamine oxide represented by Chemical Formula 1 (R is an alkyl group) in water and then adding and mixing β-glycyrrhetinic acid , wherein the total amount of water is 86 An emulsified composition of 0.0 to 98.7% by weight .
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2010054010A JP5689242B2 (en) | 2010-03-11 | 2010-03-11 | Emulsified composition and external preparation for skin containing the same |
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| JP2010054010A JP5689242B2 (en) | 2010-03-11 | 2010-03-11 | Emulsified composition and external preparation for skin containing the same |
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| JPS61112006A (en) * | 1984-11-07 | 1986-05-30 | Maruzen Seiyaku Kk | Aqueous solution of glycyrrhezic acid composition |
| JPH04264014A (en) * | 1991-02-18 | 1992-09-18 | Kao Corp | Inhibitor of sebum secretion |
| JP3566343B2 (en) * | 1994-07-06 | 2004-09-15 | 株式会社資生堂 | Percutaneous absorption enhancer and external preparation for skin |
| JPH10273423A (en) * | 1997-03-27 | 1998-10-13 | Shiseido Co Ltd | Cosmetic for hair |
| JPH11255621A (en) * | 1998-03-10 | 1999-09-21 | Shiseido Co Ltd | Cosmetic for scalp and hair |
| JP2000007584A (en) * | 1998-06-24 | 2000-01-11 | Lion Corp | Solubilization of sparingly soluble medicament and composition of skin lotion |
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