JP5856766B2 - External preparation for skin and method for producing the same - Google Patents
External preparation for skin and method for producing the same Download PDFInfo
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- JP5856766B2 JP5856766B2 JP2011140502A JP2011140502A JP5856766B2 JP 5856766 B2 JP5856766 B2 JP 5856766B2 JP 2011140502 A JP2011140502 A JP 2011140502A JP 2011140502 A JP2011140502 A JP 2011140502A JP 5856766 B2 JP5856766 B2 JP 5856766B2
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- JP
- Japan
- Prior art keywords
- skin
- external preparation
- phosphate
- palmitate
- ascorbic acid
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims description 44
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- -1 biphenyl compound Chemical class 0.000 claims description 44
- 239000004305 biphenyl Substances 0.000 claims description 36
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 32
- 235000010290 biphenyl Nutrition 0.000 claims description 31
- 239000002537 cosmetic Substances 0.000 claims description 19
- 150000002430 hydrocarbons Chemical group 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 239000011734 sodium Substances 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims description 6
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 210000003491 skin Anatomy 0.000 description 41
- 206010040880 Skin irritation Diseases 0.000 description 23
- 231100000475 skin irritation Toxicity 0.000 description 23
- 230000036556 skin irritation Effects 0.000 description 23
- 230000002087 whitening effect Effects 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 14
- 150000003839 salts Chemical class 0.000 description 10
- 239000006210 lotion Substances 0.000 description 9
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 239000000194 fatty acid Substances 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 150000004665 fatty acids Chemical class 0.000 description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 230000007794 irritation Effects 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- OYAQUBKYAKSHOA-UHFFFAOYSA-N 2-(2-hydroxy-5-propylphenyl)-4-propylphenol Chemical group CCCC1=CC=C(O)C(C=2C(=CC=C(CCC)C=2)O)=C1 OYAQUBKYAKSHOA-UHFFFAOYSA-N 0.000 description 5
- 150000000996 L-ascorbic acids Chemical class 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 230000001052 transient effect Effects 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 206010015150 Erythema Diseases 0.000 description 2
- FSYKKLYZXJSNPZ-UHFFFAOYSA-N N-methylaminoacetic acid Natural products C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 108010077895 Sarcosine Proteins 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004945 emulsification Methods 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 229940043230 sarcosine Drugs 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 0 *c(cc1)cc(-c2cc(*)ccc2O)c1O Chemical compound *c(cc1)cc(-c2cc(*)ccc2O)c1O 0.000 description 1
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- MLSJBGYKDYSOAE-DCWMUDTNSA-N L-Ascorbic acid-2-glucoside Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=C1O MLSJBGYKDYSOAE-DCWMUDTNSA-N 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 206010070835 Skin sensitisation Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 229940064004 antiseptic throat preparations Drugs 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000003093 cationic surfactant Substances 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008406 cosmetic ingredient Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N n-hexadecanoic acid Natural products CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000037307 sensitive skin Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 231100000370 skin sensitisation Toxicity 0.000 description 1
- 229940045870 sodium palmitate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000000341 volatile oil Substances 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
- 235000010493 xanthan gum Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/005—Preparations for sensitive skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
Description
本発明は、皮膚外用剤およびその製造方法に関する。 The present invention relates to an external preparation for skin and a method for producing the same.
従来、化粧料等の皮膚外用剤に美白剤を配合することが行われている。しかし、美白剤を含有する皮膚外用剤は、敏感肌の人に刺激を発現する場合がある。この刺激とは、通常、皮膚表面に接触した物質が、皮膚バリアを通過し角化細胞に至り、角化細胞を刺激し、皮膚局所に炎症反応を引き起こす一過性の刺激を言う。
そのため、美白剤を含有する皮膚外用剤の皮膚刺激性を低減するために様々な検討が行われている。たとえば特許文献１では、刺激を緩和するために、美白剤に対して特定の非イオン性界面活性剤を組み合わせた皮膚外用剤が開示されている。特許文献２では、一過性の刺激発現を抑制するために、美白剤に対して抗菌性リン脂質を組み合わせた化粧料が開示されている。
美白剤として、２，２’−ジヒドロキシ−５，５’−ジアルキル−ビフェニル等のビフェニル化合物を用いることも提案されている。該ビフェニル化合物は、メラニンの生成に関与する酵素であるチロシナーゼの活性を阻害することによりメラニンの生成を抑制し、美白効果を発揮する。そのため、同じく美白剤の１種であるハイドロキノン類に比べて安全性が高いとされており（たとえば特許文献３）、化粧料等への配合も検討されている。たとえば特許文献４では、ビフェニル化合物の溶解性を高め、使用感を向上させるために、Ｎ−アシルサルコシンアルキルを組み合わせた美白化粧料が開示されている。
Conventionally, a whitening agent has been blended into an external preparation for skin such as cosmetics. However, an external preparation for skin containing a whitening agent may develop irritation in people with sensitive skin. This irritation usually refers to a transient irritation that causes a substance in contact with the skin surface to pass through the skin barrier to reach the keratinocytes, stimulate the keratinocytes, and cause an inflammatory reaction in the skin region.
For this reason, various studies have been conducted to reduce the skin irritation of a topical skin preparation containing a whitening agent. For example, Patent Document 1 discloses a skin external preparation in which a specific nonionic surfactant is combined with a whitening agent in order to reduce irritation. Patent Document 2 discloses a cosmetic in which an antibacterial phospholipid is combined with a whitening agent in order to suppress transient expression of stimuli.
It has also been proposed to use a biphenyl compound such as 2,2′-dihydroxy-5,5′-dialkyl-biphenyl as a whitening agent. The biphenyl compound suppresses the production of melanin by inhibiting the activity of tyrosinase, an enzyme involved in the production of melanin, and exhibits a whitening effect. Therefore, it is considered to be safer than hydroquinones, which are also a kind of whitening agent (for example, Patent Document 3), and blending into cosmetics and the like is also being studied. For example, Patent Document 4 discloses a whitening cosmetic combined with N-acyl sarcosine alkyl in order to increase the solubility of the biphenyl compound and improve the feeling of use.
しかし、本発明者の検討によれば、美白剤としてビフェニル化合物を用いた場合でも、それを含有する皮膚外用剤によっては一過性の刺激が生じることがある。
なお、特許文献４では、２，２’−ジヒドロキシ−５，５’−ジアルキル−ビフェニルとＮ−アシルサルコシンアルキルとを組み合わせた美白化粧料について、皮膚刺激反応又は皮膚感作反応を示した被試験者は生じなかったとされているが、試験方法や結果は明確に示されていない。
本発明は、上記事情に鑑みてなされたものであり、美白剤である２，２’−ジヒドロキシ−５，５’−ジアルキル−ビフェニル等のビフェニル化合物を含有し、かつ皮膚刺激性の少ない皮膚外用剤およびその製造方法を提供することを目的とする。
However, according to the study of the present inventor, even when a biphenyl compound is used as a whitening agent, transient irritation may occur depending on the external preparation for skin containing the biphenyl compound.
In addition, in Patent Document 4, a test subject showing a skin irritation reaction or a skin sensitization reaction for a whitening cosmetic that is a combination of 2,2′-dihydroxy-5,5′-dialkyl-biphenyl and N-acyl sarcosine alkyl. However, the test methods and results are not clearly shown.
The present invention has been made in view of the above circumstances, and contains a biphenyl compound such as 2,2′-dihydroxy-5,5′-dialkyl-biphenyl, which is a whitening agent, and has a low skin irritation. An object is to provide an agent and a method for producing the same.
本発明者らは、上記課題を解決すべく鋭意研究した結果、美白剤である２，２’−ジヒドロキシ−５，５’−ジアルキル−ビフェニル等のビフェニル化合物とアスコルビン酸−２−リン酸−６−パルミチン酸塩を組み合わせることによって、該ビフェニル化合物により誘発される皮膚刺激性が緩和されることを見出し、本発明を完成するに至った。
本発明は、以下の態様を有する。
［１］下記一般式（１）で表されるビフェニル化合物０．１〜５質量％と、アスコルビン酸−２−リン酸−６−パルミチン酸塩０．０１〜５質量％とを含有することを特徴とする皮膚外用剤。
As a result of diligent research to solve the above-mentioned problems, the present inventors have found that a whitening agent such as a biphenyl compound such as 2,2′-dihydroxy-5,5′-dialkyl-biphenyl and ascorbic acid-2-phosphate-6. -It discovered that the skin irritation induced | guided | derived by this biphenyl compound was relieve | moderated by combining palmitate, and came to complete this invention.
The present invention has the following aspects.
[1] It contains 0.1 to 5% by mass of a biphenyl compound represented by the following general formula (1) and 0.01 to 5% by mass of ascorbyl 2-phosphate-6-palmitate. A topical skin preparation.
［２］前記ビフェニル化合物に対する前記アスコルビン酸−２−リン酸−６−パルミチン酸塩の質量比が０．００５〜１である、 [１]に記載の皮膚外用剤。
［３］前記アスコルビン酸−２−リン酸−６−パルミチン酸塩が、アスコルビン酸−２−リン酸−６−パルミチン酸ナトリウムである、［１］または［２］に記載の皮膚外用剤。
［４］化粧料である、［１］〜［３］のいずれか一項に記載の皮膚外用剤。
［５］下記一般式（１）で表されるビフェニル化合物とアスコルビン酸−２−リン酸−６−パルミチン酸塩とを、当該皮膚外用剤全量中の前記ビフェニル化合物の含有量が０．１〜５質量％、前記アスコルビン酸−２−リン酸−６−パルミチン酸塩の含有量が０．０１〜５質量％となるように配合することを特徴とする皮膚外用剤の製造方法。
[2] The skin external preparation according to [1], wherein a mass ratio of the ascorbic acid-2-phosphate-6-palmitate to the biphenyl compound is 0.005 to 1.
[3] The external preparation for skin according to [1] or [2], wherein the ascorbic acid-2-phosphate-6-palmitate is sodium ascorbate-2-phosphate-6-palmitate.
[4] The external preparation for skin according to any one of [1] to [3], which is a cosmetic.
[5] A biphenyl compound represented by the following general formula (1) and ascorbic acid-2-phosphate-6-palmitate are used in an amount of 0.1 to 0.1% in the total amount of the external preparation for skin. A method for producing a skin external preparation, comprising 5% by mass and an ascorbic acid-2-phosphate-6-palmitate content of 0.01 to 5% by mass.
［６］前記ビフェニル化合物に対する前記アスコルビン酸−２−リン酸−６−パルミチン酸塩の質量比が０．００５〜１となるように配合する、［５］に記載の皮膚外用剤の製造方法。 [6] The method for producing an external preparation for skin according to [5], which is blended so that a mass ratio of the ascorbic acid-2-phosphate-6-palmitate to the biphenyl compound is 0.005 to 1.
なお、アスコルビン酸−２−リン酸−６−パルミチン酸塩は、アスコルビン酸誘導体であり、美白作用、抗酸化作用、コラーゲン合成促進作用等の効能効果を呈する化合物として知られている。しかし、前記一般式（１）で表されるビフェニル化合物を含む皮膚外用剤による一過性の刺激の発現を、アスコルビン酸−２−リン酸−６−パルミチン酸塩を配合することにより抑制できることの開示や示唆は特許文献１〜４のいずれの文献にもない。 In addition, ascorbic acid-2-phosphate-6-palmitate is an ascorbic acid derivative and is known as a compound that exhibits efficacy effects such as whitening action, antioxidant action, and collagen synthesis promoting action. However, the expression of transient irritation caused by the external preparation for skin containing the biphenyl compound represented by the general formula (1) can be suppressed by blending ascorbic acid-2-phosphate-6-palmitate. There is no disclosure or suggestion in any of Patent Documents 1 to 4.
本発明によれば、美白剤である２，２’−ジヒドロキシ−５，５’−ジアルキル−ビフェニル等のビフェニル化合物を含有し、かつ皮膚刺激性の少ない皮膚外用剤およびその製造方法を提供できる。 ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation which contains biphenyl compounds, such as 2,2'-dihydroxy-5,5'-dialkyl-biphenyl which is a whitening agent, and has little skin irritation, and its manufacturing method can be provided.
本発明の皮膚外用剤は、下記一般式（１）で表されるビフェニル化合物（以下、ビフェニル化合物（１）という。）、アスコルビン酸−２−リン酸−６−パルミチン酸塩と、を含有する。 The skin external preparation of this invention contains the biphenyl compound (henceforth biphenyl compound (1)) represented by the following general formula (1), and ascorbic acid-2-phosphate-6-palmitate. .
＜ビフェニル化合物（１）＞
前記一般式（１）中、Ｒは水素原子であっても炭化水素基であってもよい。
Ｒの炭化水素基は、直鎖状でも分岐鎖状でもよい。該炭化水素基は、飽和炭化水素基（アルキル基）でも不飽和炭化水素基でもよいが、安定性の面からアルキル基が好ましい。該炭化水素基の炭素数は１〜５が好ましい。該炭化水素基のうち、直鎖状の炭化水素基の具体例としては、メチル基、エチル基、ｎ−プロピル基、ｎ−ブチル基、アリル基等が挙げられ、分岐鎖状の炭化水素基の具体例としては、イソプロピル基、ｔ−ブチル基、イソペンチル基等が挙げられるが、これに限定されない。
Ｒとしては、水素原子またはアルキル基が好ましく、直鎖状のアルキル基がより好ましく、ｎ−プロピル基が特に好ましい。すなわちビフェニル化合物（１）としては２，２’−ジヒドロキシ−５，５’−ジ−ｎ−プロピル−ビフェニルが特に好ましい。
<Biphenyl compound (1)>
In the general formula (1), R may be a hydrogen atom or a hydrocarbon group.
The hydrocarbon group for R may be linear or branched. The hydrocarbon group may be a saturated hydrocarbon group (alkyl group) or an unsaturated hydrocarbon group, but an alkyl group is preferable from the viewpoint of stability. As for carbon number of this hydrocarbon group, 1-5 are preferred. Among the hydrocarbon groups, specific examples of the linear hydrocarbon group include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an allyl group, and the like, and a branched hydrocarbon group. Specific examples of these include, but are not limited to, an isopropyl group, a t-butyl group, and an isopentyl group.
R is preferably a hydrogen atom or an alkyl group, more preferably a linear alkyl group, and particularly preferably an n-propyl group. That is, 2,2′-dihydroxy-5,5′-di-n-propyl-biphenyl is particularly preferable as the biphenyl compound (1).
ビフェニル化合物（１）としては、１種を単独で用いても２種以上を併用してもよい。
本発明の皮膚外用剤中、ビフェニル化合物（１）の含有量は、皮膚外用剤全量に対して０．１〜５質量％であり、０．３〜３質量％が好ましい。ビフェニル化合物（１）の含有量が０．１質量％未満であると、ビフェニル化合物（１）による美白効果が充分に得られず、５質量％を超えて配合してもそれに見合った美白効果がないことが多い。
As a biphenyl compound (1), 1 type may be used independently or 2 or more types may be used together.
In the external preparation for skin of the present invention, the content of the biphenyl compound (1) is 0.1 to 5 mass%, preferably 0.3 to 3 mass%, based on the total amount of external preparation for skin. When the content of the biphenyl compound (1) is less than 0.1% by mass, the whitening effect by the biphenyl compound (1) is not sufficiently obtained, and even if it exceeds 5% by mass, the whitening effect commensurate with it is obtained. Often not.
＜アスコルビン酸−２−リン酸−６−パルミチン酸塩＞
アスコルビン酸−２−リン酸−６−パルミチン酸塩は、アスコルビン酸の２位の炭素原子に結合した水酸基にリン酸がエステル結合し、６位の炭素原子に結合した水酸基にパルミチン酸がエステル結合し、前記リン酸基中のリン原子に結合した水酸基２つとアスコルビン酸の３位の炭素原子に結合した水酸基とのいずれか少なくとも１つから水素原子が解離して塩を形成した化合物であり、塩としては、ナトリウム塩、カリウム塩等が挙げられる。たとえばアスコルビン酸−２−リン酸−６−パルミチン酸ナトリウムは、下記化学式で表される。
アスコルビン酸−２−リン酸−６−パルミチン酸塩としては、特に皮膚外用剤が化粧料である場合、アスコルビン酸−２−リン酸−６−パルミチン酸ナトリウムが扱いやすく好ましい。
<Ascorbic acid-2-phosphate-6-palmitate>
Ascorbic acid-2-phosphate-6-palmitate has phosphoric acid ester-bonded to the hydroxyl group bonded to the 2nd carbon atom of ascorbic acid, and palmitic acid ester bonded to the hydroxyl group bonded to the 6th carbon atom And a compound in which a hydrogen atom is dissociated from at least one of two hydroxyl groups bonded to a phosphorus atom in the phosphate group and a hydroxyl group bonded to the 3-position carbon atom of ascorbic acid to form a salt, Examples of the salt include sodium salt and potassium salt. For example, sodium ascorbyl-2-phosphate-6-palmitate is represented by the following chemical formula.
As the ascorbic acid-2-phosphate-6-palmitate, ascorbic acid-2-phosphate-6-palmitate is preferable because it is a cosmetic preparation, particularly when the skin external preparation is a cosmetic.
アスコルビン酸−２−リン酸−６−パルミチン酸塩としては、１種を単独で用いても２種以上を併用してもよい。
本発明の皮膚外用剤中、アスコルビン酸−２−リン酸−６−パルミチン酸塩の含有量は、皮膚外用剤全量に対して０．０１〜５質量％であり、０．５〜３質量％が好ましい。アスコルビン酸−２−リン酸−６−パルミチン酸塩をこのような量で皮膚外用剤に配合することで、皮膚刺激性の少ない皮膚外用剤とすることができる。一方、該含有量が０．０１質量％未満であると、ビフェニル化合物（１）による皮膚刺激の誘発を充分に抑制できないおそれがある。また５質量％を超えて配合しても見合った抑制効果が増加せず、経済的ではない。
さらに、前述の含有量の範囲内において、ビフェニル化合物（１）に対するアスコルビン酸−２−リン酸−６−パルミチン酸塩の質量比を、好ましくは０．００５〜１、より好ましくは０．１〜０．５の範囲にすると、少ないアスコルビン酸−２−リン酸−６−パルミチン酸塩の添加量にもかかわらず、より皮膚刺激性の少ない皮膚外用剤とすることができる。
As ascorbic acid-2-phosphate-6-palmitate may be used alone or in combination of two or more.
In the external preparation for skin of the present invention, the content of ascorbyl 2-phosphate-6-palmitate is 0.01 to 5% by mass, and 0.5 to 3% by mass with respect to the total amount of external preparation for skin. Is preferred. By blending ascorbic acid-2-phosphate-6-palmitate into the skin external preparation in such an amount, it can be made into a skin external preparation with little skin irritation. On the other hand, when the content is less than 0.01% by mass, induction of skin irritation by the biphenyl compound (1) may not be sufficiently suppressed. Moreover, even if it mixes exceeding 5 mass%, the suitable inhibitory effect does not increase and it is not economical.
Furthermore, within the above-described content range, the mass ratio of ascorbic acid-2-phosphate-6-palmitate to biphenyl compound (1) is preferably 0.005 to 1, more preferably 0.1 to 0.1. When it is in the range of 0.5, it is possible to obtain a skin external preparation with less skin irritation, despite the small amount of ascorbic acid-2-phosphate-6-palmitate added.
＜その他の任意成分＞
本発明の皮膚外用剤は、本発明の効果を損なわない範囲で、アスコルビン酸およびその塩、ならびにアスコルビン酸−２−リン酸−パルミチン酸塩以外のアスコルビン酸誘導体から選ばれる少なくとも１種を配合してもよい。
アスコルビン酸の塩としては、ナトリウム塩、カリウム塩等が挙げられる。
アスコルビン酸−２−リン酸−パルミチン酸塩以外のアスコルビン酸誘導体としては、アスコルビン酸−３−リン酸−６−高級脂肪酸およびその塩、アスコルビン酸−６−高級脂肪酸およびその塩、アスコルビン酸−２，６−ジ高級脂肪酸およびその塩、アスコルビン酸−２，３，５，６−テトラ高級脂肪酸およびその塩、アスコルビン酸−２−硫酸およびその塩、アスコルビル−２−グルコシド等が挙げられる。塩としては、ナトリウム塩、カリウム塩等が挙げられる。高級脂肪酸としては、炭素数８〜２２の脂肪酸が挙げられる。
これらのアスコルビン酸誘導体の具体例として、アスコルビン酸−３−リン酸−６−パルミチン酸ナトリウム、６−パルミチン酸アスコルビル、２，６−ジパルミチン酸アスコルビル、２，３，５，６−テトライソパルミチン酸アスコルビル、アスコルビン酸−２−硫酸二ナトリウム、アスコルビン酸−２−グルコシド等が挙げられる。
<Other optional components>
The skin external preparation of the present invention contains at least one selected from ascorbic acid and its salts, and ascorbic acid derivatives other than ascorbic acid-2-phosphate-palmitate, as long as the effects of the present invention are not impaired. May be.
Examples of ascorbic acid salts include sodium salts and potassium salts.
Ascorbic acid derivatives other than ascorbic acid-2-phosphate-palmitate include ascorbic acid-3-phosphate-6-higher fatty acid and its salt, ascorbic acid-6-higher fatty acid and its salt, ascorbic acid-2 , 6-di higher fatty acid and its salt, ascorbic acid-2,3,5,6-tetra higher fatty acid and its salt, ascorbic acid-2-sulfuric acid and its salt, ascorbyl-2-glucoside and the like. Examples of the salt include sodium salt and potassium salt. Examples of higher fatty acids include fatty acids having 8 to 22 carbon atoms.
Specific examples of these ascorbic acid derivatives include sodium ascorbyl-3-phosphate-6-palmitate, ascorbyl 6-palmitate, ascorbyl 2,6-dipalmitate, 2,3,5,6-tetraisopalmitin Examples include acid ascorbyl, ascorbic acid-2-sodium sulfate, ascorbic acid-2-glucoside and the like.
本発明の皮膚外用剤は、上記のほか、必要に応じて、本発明の効果を損なわない範囲で、皮膚外用剤に通常用いられる成分、たとえば皮膚外用剤として薬学的に許容され得る担体、添加剤等を含有してもよい。
このような成分としては、たとえば、炭化水素類、天然油脂類、脂肪酸類、高級アルコール類、アルキルグリセリルエーテル類、エステル類、シリコーン油類、多価アルコール類、一価の低級アルコール類、糖類、高分子類、陰イオン界面活性剤、陽イオン界面活性剤、両性界面活性剤、非イオン界面活性剤、天然系界面活性剤、紫外線吸収剤、粉体類、色材類、アミノ酸類、ペプチド類、ビタミン類、ビタミン様作用因子類、防腐剤、酸化防止剤、金属イオン封鎖剤、保湿剤、抗炎症剤、ｐＨ調整剤、塩類、有機酸類、精油類、テルペン類、香料、水等が挙げられる。
In addition to the above, the external preparation for skin of the present invention contains components usually used for external preparation for skin, for example, a pharmaceutically acceptable carrier as an external preparation for skin, as long as the effects of the present invention are not impaired. An agent or the like may be contained.
Examples of such components include hydrocarbons, natural fats and oils, fatty acids, higher alcohols, alkyl glyceryl ethers, esters, silicone oils, polyhydric alcohols, monovalent lower alcohols, saccharides, Polymers, anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, natural surfactants, UV absorbers, powders, color materials, amino acids, peptides Vitamins, vitamin-like agents, antiseptics, antioxidants, sequestering agents, moisturizers, anti-inflammatory agents, pH adjusters, salts, organic acids, essential oils, terpenes, fragrances, water, etc. It is done.
本発明の皮膚外用剤としては、化粧料および医薬品が挙げられる。
本発明の皮膚外用剤が化粧料である場合、さらに、既存の化粧品原料を一般的な濃度で添加することもできる。たとえば、化粧品原料基準第二版注解、日本公定書教会編、１９８４（薬事日報社）、化粧品原料基準外成分規格、厚生省薬務局審査課監修、１９９３（薬事日報社）、化粧品原料基準外成分規格追補、厚生省薬務局審査課監修、１９９３（薬事日報社）、化粧品種別許可基準、厚生省薬務局審査課監修、１９９３（薬事日報社）、化粧品種別配合成分規格、厚生省薬務局審査課監修、１９９７（薬事日報社）、および化粧品原料辞典、平成３年（日光ケミカルズ）等に記載されている全ての化粧品原料を使用することができる。
Examples of the external preparation for skin of the present invention include cosmetics and pharmaceuticals.
When the skin external preparation of the present invention is a cosmetic, an existing cosmetic raw material can be added at a general concentration. For example, Cosmetic Material Standards Second Edition Commentary, Japan Official Church Church, 1984 (Pharmaceutical Daily Report), Cosmetic Raw Material Standards Independent Component Standard, Ministry of Health and Welfare Pharmaceutical Affairs Bureau Supervision Division, 1993 (Pharmaceutical Daily Report) Standard supplement, supervised by Ministry of Health and Welfare Pharmacy Examination Division, 1993 (Pharmaceutical Daily), permission standards by cosmetics type, supervised by Ministry of Health and Welfare Pharmacy Examination Division, 1993 (Pharmaceutical Daily), Standards for Cosmetic Ingredients, Examination Division by Ministry of Health and Welfare All cosmetic raw materials described in the supervision, 1997 (Pharmaceutical Daily), cosmetic raw material dictionary, 1991 (Nikko Chemicals), etc. can be used.
本発明の皮膚外用剤の剤型としては、使用時に皮膚に接触させて用いられるものであれば特に制限はなく、用途に応じて適宜設定される。たとえばローション、乳液、クリーム、パック等に適用することが出来る。 The dosage form of the external preparation for skin of the present invention is not particularly limited as long as it is used in contact with the skin at the time of use, and is appropriately set according to the use. For example, it can be applied to lotions, emulsions, creams, packs and the like.
本発明の皮膚外用剤は、前記ビフェニル化合物（１）、前記アスコルビン酸−２−リン酸−６−パルミチン酸塩およびその他の任意成分を配合して製剤化することにより製造される。製剤化は、剤型に応じて、常法に従って実施できる。 The skin external preparation of this invention is manufactured by mix | blending and formulating the said biphenyl compound (1), the said ascorbic acid-2-phosphate-6-palmitate, and another arbitrary component. Formulation can be performed according to a conventional method according to the dosage form.
上記のようにビフェニル化合物（１）とアスコルビン酸−２−リン酸−６−パルミチン酸塩を配合することにより、ビフェニル化合物（１）による一過性の皮膚刺激の発現が抑制された皮膚刺激性の少ない皮膚外用剤が得られる。
このため、本発明は、化粧料や医薬品を含む皮膚外用剤全般に有用であり、中でも化粧料に好適である。特に乳化剤形のものは調製しやすく好ましい。
Skin irritation in which expression of transient skin irritation by biphenyl compound (1) is suppressed by blending biphenyl compound (1) and ascorbyl 2-phosphate-6-palmitate as described above An external preparation for skin with a low content can be obtained.
Therefore, the present invention is useful for all external preparations for skin including cosmetics and pharmaceuticals, and is particularly suitable for cosmetics. The emulsifier type is particularly easy to prepare and is preferred.
以下、実施例に基づいて本発明をより具体的に説明するが、本発明はこれらの実施例に限定されるものではない。
後述する各実施例、比較例および対照例で得られた皮膚外用剤（ローション）についての皮膚刺激性の評価は以下の手順で実施した。
＜皮膚刺激性の評価方法＞
得られたローションについて、モルモット損傷皮膚モデル（ハートレー白色種、雌、３００〜４００ｇ、剃毛後テープストリッピング３回）１群５匹を用いて、２４時間クローズドパッチによる皮膚刺激性を調べた。皮膚刺激性の評価基準は、ドレーズの基準を用いた。即ち、以下の基準により皮膚刺激性を評価した。
スコア２：浮腫を伴う反応。
スコア１：明らかな紅斑を伴う反応。
スコア０．５：疑わしい紅斑を伴う反応。
スコア０：無反応。
EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example, this invention is not limited to these Examples.
Evaluation of skin irritation of the topical skin preparation (lotion) obtained in each Example, Comparative Example and Control Example described below was carried out according to the following procedure.
<Method for evaluating skin irritation>
The obtained lotion was examined for skin irritation caused by a closed patch for 24 hours using 5 guinea pig damaged skin models (Hartley white species, female, 300-400 g, 3 times tape stripping after shaving) 1 group. The evaluation criteria for skin irritation was the Draise standard. That is, skin irritation was evaluated according to the following criteria.
Score 2: reaction with edema.
Score 1: reaction with obvious erythema.
Score 0.5: reaction with suspicious erythema.
Score 0: no response.
〔実施例１、比較例１、対照例１〕
表１に示す組成（単位：質量％）のローションを以下の手順で調製した。
まず、以下の手順でＡ相、Ｂ相、Ｃ相を調製した。
Ａ相：表１に示すＡ相の成分のうち、２，２’−ジヒドロキシ−５，５’−ジ−ｎ−プロピル−ビフェニル、アスコルビン酸−２−リン酸−６−パルミチン酸ナトリウムをその他の成分（油性成分）と混合し、加熱融解して８０℃に保った。
Ｂ相：表１に示すＢ相の各成分を混合し、加熱融解して８０℃に保った。
Ｃ相：精製水にアルギニンを溶解した。
次に、Ｂ相（水相）にＡ相（油相）を加え、予備乳化を行い、ホモミキサーで均一乳化し、乳化後、よくかきまぜながら、３０℃まで冷却し、さらにＣ相を加えてローションを得た。
得られたローションを用いて皮膚刺激性の評価を行った。その結果（当該スコアに該当すると判定されたモルモット損傷皮膚モデルの数）を表１に併記した。
[Example 1, Comparative Example 1, Control Example 1]
A lotion having the composition (unit: mass%) shown in Table 1 was prepared by the following procedure.
First, A phase, B phase, and C phase were prepared in the following procedures.
Phase A: Among the components of Phase A shown in Table 1, 2,2′-dihydroxy-5,5′-di-n-propyl-biphenyl, ascorbic acid-2-phosphate-6-sodium palmitate It mixed with the component (oil-based component), heated and melted, and kept at 80 ° C.
Phase B: The components of Phase B shown in Table 1 were mixed, heated and melted, and kept at 80 ° C.
Phase C: Arginine was dissolved in purified water.
Next, add A phase (oil phase) to B phase (water phase), pre-emulsify, homogenize uniformly with homomixer, and after emulsification, cool to 30 ° C while stirring well and add C phase. Got lotion.
Skin irritation was evaluated using the obtained lotion. The results (number of guinea pig injured skin models determined to correspond to the score) are also shown in Table 1.
上記結果に示すとおり、皮膚刺激性を示さない対照例１の組成に２，２’−ジヒドロキシ−５，５’−ジ−ｎ−プロピル−ビフェニルを配合した比較例１は皮膚刺激性を示していたが、さらにアスコルビン酸−２−リン酸−６−パルミチン酸ナトリウムを配合した実施例１は、対照例１と同様、皮膚刺激性を示さなかった。 As shown in the above results, Comparative Example 1 in which 2,2′-dihydroxy-5,5′-di-n-propyl-biphenyl was blended with the composition of Control Example 1 that did not show skin irritation showed skin irritation. However, Example 1 in which sodium ascorbyl 2-phosphate-6-palmitate was further blended did not show skin irritation as in Control Example 1.
〔実施例２〜４、比較例４、対照例２〕
表２に示す組成（単位：質量％）のローションを以下の手順で調製した。
まず、以下の手順でＡ相、Ｂ相、Ｃ相を調製した。
Ａ相：２，２’−ジヒドロキシ−５，５’−ジ−ｎ−プロピル−ビフェニル、アスコルビン酸−２−リン酸−６−パルミチン酸ナトリウムをその他の成分（油性成分）と混合し、加熱融解して８０℃に保った。
Ｂ相：各成分を混合し、加熱融解して８０℃に保った。
Ｃ相：精製水に水酸化カリウムを溶解した。
次に、Ｂ相（水相）にＡ相（油相）を加え、予備乳化を行い、ホモミキサーで均一乳化し、乳化後、よくかきまぜながら、３０℃まで冷却し、さらにＣ相を加えてローションを得た。
得られたローションを用いて皮膚刺激性の評価を行った。その結果（当該スコアに該当すると判定されたモルモット損傷皮膚モデルの数）を表２に併記した。
[Examples 2 to 4, Comparative Example 4, Control Example 2]
A lotion having the composition (unit: mass%) shown in Table 2 was prepared by the following procedure.
First, A phase, B phase, and C phase were prepared in the following procedures.
Phase A: 2,2′-dihydroxy-5,5′-di-n-propyl-biphenyl, sodium ascorbyl-2-phosphate-6-palmitate is mixed with other components (oil component), and heated to melt And kept at 80 ° C.
Phase B: Each component was mixed, heated and melted and kept at 80 ° C.
Phase C: Potassium hydroxide was dissolved in purified water.
Next, add A phase (oil phase) to B phase (water phase), pre-emulsify, homogenize uniformly with homomixer, and after emulsification, cool to 30 ° C while stirring well and add C phase. Got lotion.
Skin irritation was evaluated using the obtained lotion. The results (number of guinea pig injured skin models determined to correspond to the score) are also shown in Table 2.
上記結果に示すとおり、皮膚刺激性を示さない対照例２の組成に２，２’−ジヒドロキシ−５，５’−ジ−ｎ−プロピル−ビフェニルを配合した比較例２は皮膚刺激性を示していたが、さらにアスコルビン酸−２−リン酸−６−パルミチン酸ナトリウムを配合した実施例２は、対照例２と同様、皮膚刺激性を示さなかった。 As shown in the above results, Comparative Example 2 in which 2,2′-dihydroxy-5,5′-di-n-propyl-biphenyl was blended with the composition of Control Example 2 that did not show skin irritation showed skin irritation. However, Example 2 further blended with sodium ascorbyl-2-phosphate-6-palmitate did not show skin irritation as in Control Example 2.
なお、上記各実施例、比較例および対照例で用いた原料において、括弧内のＥ．Ｏ．はポリオキシエチレンの略であり、Ｅ．Ｏ．の前の数値は、ポリオキシエチレンユニットにおけるオキシエチレン基の平均重合度を示す。
カルボキシビニルポリマーとしては、ＣＡＢＯＰＯＬ９８０（商品名、ｎｏｖｅｏｎ製を用いた。
キサンタンガムとしては、ＫＥＬＴＲＯＬ ＣＧ-ＳＦＴ（三晶）を用いた。
In the raw materials used in the above Examples, Comparative Examples and Control Examples, E. O. Is an abbreviation for polyoxyethylene. O. The numerical value before indicates the average degree of polymerization of oxyethylene groups in the polyoxyethylene unit.
As the carboxyvinyl polymer, CABOPOL980 (trade name, manufactured by Noveon) was used.
As xanthan gum, KELTROL CG-SFT (Tricrystal) was used.
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