JP6289896B2 - Topical skin preparation - Google Patents
Topical skin preparation Download PDFInfo
- Publication number
- JP6289896B2 JP6289896B2 JP2013269637A JP2013269637A JP6289896B2 JP 6289896 B2 JP6289896 B2 JP 6289896B2 JP 2013269637 A JP2013269637 A JP 2013269637A JP 2013269637 A JP2013269637 A JP 2013269637A JP 6289896 B2 JP6289896 B2 JP 6289896B2
- Authority
- JP
- Japan
- Prior art keywords
- skin
- external preparation
- acid
- heat shock
- shock protein
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229960005078 sorbitan sesquioleate Drugs 0.000 description 1
- 229940032094 squalane Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- DXNCZXXFRKPEPY-UHFFFAOYSA-N tridecanedioic acid Chemical compound OC(=O)CCCCCCCCCCCC(O)=O DXNCZXXFRKPEPY-UHFFFAOYSA-N 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
- 239000001993 wax Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000012138 yeast extract Substances 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
Landscapes
- Cosmetics (AREA)
Description
本発明はヒートショックプロテイン産生成分の皮膚への浸透を促し、肌状態を改善する効果を有する皮膚外用剤に関する。 The present invention relates to an external preparation for skin that has an effect of improving the skin condition by promoting the penetration of heat shock protein-producing components into the skin.
ヒートショックプロテインは、細胞が熱や紫外線等のストレスにさらされた時に発現し、細胞を保護するタンパク質の一群であり、その分子量によりそれぞれの分子に名前がつけられており、例えばHSP60、70、90はそれぞれ分子量60、70、90kDaのタンパク質を指す。ヒートショックプロテインに関しては、ヒートショックプロテインおよびヒートショックプロテイン因子を産生させる酵母抽出液を含む皮膚外用剤により、紫外線、熱などの外的刺激から皮膚を保護し、損傷を受けた皮膚を修復し、改善することが報告されている(例えば、特許文献1参照)。
また、紫外線や乾燥、熱、低温などの外的環境ストレスに対して、皮膚細胞の修復や保護効果を有することにより、皮膚のバリヤー機能を向上させ、肌老化や肌あれを改善、予防する効果を有する抗皮膚ストレス用化粧料としては、海洋プランクトン、アルテミア(Artemia Salina 和名:ホウネンエビ)の孵化直前の耐久卵から水抽出した活性エキス成分を配合した化粧料(例えば、特許文献2参照)、紅藻の含水アルコール抽出物により、ストレス蛋白質の合成を誘発できる技術が知られている(例えば、特許文献3参照)。
Heat shock proteins are a group of proteins that are expressed when cells are exposed to stress such as heat and ultraviolet rays and protect the cells. Each molecule is named according to its molecular weight. For example, HSP60, 70, 90 refers to proteins with molecular weights of 60, 70, and 90 kDa, respectively. With regard to heat shock protein, skin external preparations containing yeast extract that produces heat shock protein and heat shock protein factor protect the skin from external stimuli such as ultraviolet rays and heat, repair damaged skin, Improvement has been reported (for example, see Patent Document 1).
In addition, it has the effect of improving and preventing skin aging and rough skin by improving skin barrier function by repairing and protecting skin cells against external environmental stresses such as ultraviolet rays, drying, heat, and low temperature. As an anti-skin stress cosmetic material having a composition containing an active extract component extracted from a durable egg immediately before the hatching of marine plankton and artemia (Artemia S alina Japanese name: Hoonen shrimp) (see, for example, Patent Document 2) ), And a technique capable of inducing the synthesis of stress protein by a hydroalcoholic extract of red algae (see, for example, Patent Document 3).
しかしながら、外的環境ストレスに対応するためのヒートショックプロテイン又はヒートショックプロテイン因子を産生する成分を含有した皮膚外用剤が開発されているが、これらの成分が皮膚に十分浸透せず、十分な効果を発揮しない場合が存し、ヒートショックプロテイン又はヒートショックプロテイン因子を産生する成分の効果が発揮できるよう十分浸透させる技術が求められていた。 However, skin external preparations containing ingredients that produce heat shock proteins or heat shock protein factors to cope with external environmental stresses have been developed, but these ingredients do not penetrate the skin sufficiently and have sufficient effects However, there has been a demand for a technique that allows sufficient penetration so that the effects of heat shock protein or a component that produces heat shock protein factor can be exerted.
本発明は、このような状況下なされたものであり、ヒートショックプロテイン産生促進成分を皮膚に十分浸透させ、物理的皮膚の損傷を改善し、肌状態を改善する皮膚外用剤を提供することを課題とする。 The present invention has been made under such circumstances, and provides a skin external preparation that sufficiently penetrates the skin with a heat shock protein production promoting component, improves physical skin damage, and improves the skin condition. Let it be an issue.
本発明者らは、肌状態を改善可能な皮膚外用剤を提供すべく研究を進め、意外にも、ヒートショックプロテイン産生促進成分と、二価カルボン酸1種又は2種以上と水酸基価から算出した平均重合度が2〜15のポリグリセリンとのオリゴマーエステル、及びグリセリン、平均重合度2〜4のポリグリセリンからなる群から選択される一種又2種以上とを含む皮膚外用剤がヒートショックプロテイン産生促進成分の皮膚への浸透を促進し、肌状態を改善することを見出し、本発明を完成させた。すなわち、本発明は以下に示すとおりである。
<1> 下記成分A、B及びCを含有する皮膚外用剤。
A)ヒートショックプロテイン産生促進成分
B)二価カルボン酸1種又は2種以上と水酸基価から算出した平均重合度が2〜15のポリグリセリンとのオリゴマーエステル
C)グリセリン、平均重合度2〜4のポリグリセリンからなる群から選択される一種又は2種以上
<2>二価カルボン酸が炭素数6〜22の直鎖、分岐鎖、若しくは環状構造を含む二価カルボン酸であることを特徴とする<1>記載の皮膚外用剤
<3>二価カルボン酸1種又は2種以上と水酸基価から算出した平均重合度が2〜15のポリグリセリンとのオリゴマーエステルの含有量が皮膚外用剤全量に対して0.01〜4.0質量%であることを特徴とする<1>または<2>記載の皮膚外用剤
<4>実質的に油剤を含有しないことを特徴とする<1>〜<3>記載の皮膚外用剤
<5>化粧料であることを特徴とする<1>〜<4>のいずれか1項に記載の皮膚外用剤
The present inventors have advanced research to provide a skin external preparation capable of improving the skin condition, and surprisingly calculated from a heat shock protein production promoting component, one or more divalent carboxylic acids and a hydroxyl value. A skin external preparation containing an oligomeric ester with a polyglycerol having an average polymerization degree of 2 to 15 and one or more selected from the group consisting of glycerol and a polyglycerol having an average polymerization degree of 2 to 4 is a heat shock protein. It has been found that the production promoting component promotes the penetration of the skin into the skin and improves the skin condition, and the present invention has been completed. That is, the present invention is as follows.
<1> A skin external preparation containing the following components A, B and C.
A) Heat shock protein production promoting component B) Oligomer ester of polyglycerin having an average degree of polymerization of 2 to 15 calculated from one or more divalent carboxylic acids and a hydroxyl value C) Glycerin, average degree of polymerization 2 to 4 1 or 2 or more types selected from the group consisting of polyglycerin <2> The divalent carboxylic acid is a divalent carboxylic acid containing a linear, branched or cyclic structure having 6 to 22 carbon atoms. <1> The external preparation for skin <3> The content of oligomer ester of polyglycerol having an average degree of polymerization of 2 to 15 calculated from one or more divalent carboxylic acids and a hydroxyl value is the total amount of external preparation for skin <1> or <2> according to <1> or <2>, characterized in that the content is 0.01 to 4.0% by mass with respect to <1> to <1> to <3> described Hadagaiyo agent <5> characterized in that it is a cosmetic <1> to the skin external preparation according to any one of <4>
以下、本発明の皮膚外用剤について説明する。 Hereinafter, the skin external preparation of the present invention will be described.
(1)本発明の皮膚外用剤の必須成分であるヒートショックプロテイン産生促進成分
本発明の皮膚外用剤は、その必須成分としてヒートショックプロテイン産生促進成分を含有する。このようなヒートショックプロテイン産生促進成分としては、ヒートショックプロテイン産生促進成分として皮膚外用剤に使用できるものであれば特段限定されないが、具体的にはウコン、芍薬、セイヨウシロヤナギ、甘草、モモの抽出物等の植物抽出物が例示でき、これらの抽出物として用いる植物の根、茎、枝、葉、種、全草の単独の部位を用いてもよいし、2部位以上を用いてもよい。そのまま粉砕、又は乾燥したものを用いてもよい。抽出溶媒としては、極性溶媒を用いた抽出物が好ましく例示できる。前記抽出溶媒としては、水、エタノ−ル、イソプロピルアルコ−ル、ブタノ−ルなどのアルコ−ル類、1,3−ブタンジオ−ル、ポリプロピレングリコ−ルなどの多価アルコ−ル類、アセトン、メチルエチルケトンなどのケトン類、ジエチルエ−テル、テトラヒドロフランなどのエ−テル類から選択される1種乃至は2種以上の極性溶媒で抽出した抽出液、抽出液を乾燥し粉末にしたものを用いることができる。これらの粉砕物、抽出物、乾燥物等をカラムや溶液間の分配により精製し、有効成分を高めたもの等を用いることもできる。
(1) Heat shock protein production promoting component as an essential component of the external preparation for skin of the present invention The external preparation for skin of the present invention contains a heat shock protein production promoting component as its essential component. Such a heat shock protein production promoting component is not particularly limited as long as it can be used as a heat shock protein production promoting component in an external preparation for skin, but specifically, extraction of turmeric, glaze, white willow, licorice, peach Plant extracts such as products can be exemplified, and a single part of the root, stem, branch, leaf, seed, whole plant of the plant used as these extracts may be used, or two or more parts may be used. You may use what was grind | pulverized or dried as it is. As the extraction solvent, an extract using a polar solvent can be preferably exemplified. Examples of the extraction solvent include water, ethanol, isopropyl alcohol, butanol, and other polyhydric alcohols such as 1,3-butanediol and polypropylene glycol, acetone, Extracts extracted with one or two or more polar solvents selected from ketones such as methyl ethyl ketone, ethers such as diethyl ether and tetrahydrofuran, and those obtained by drying the extract into powder it can. These pulverized product, extract, dried product and the like can be purified by partitioning between columns and solutions to increase the active ingredients.
ウコンとしては、ショウガ科のCurcuma domestica Val.の根茎部の抽出物、芍薬としては、ボタン科のPaeoniaの根部の抽出物、セイヨウシロヤナギとしては、ヤナギ科ヤナギ属のSalix Albaの葉の抽出物、甘草としては、マメ科カンゾウ属のGlycyrrhizaの根の抽出物、モモとしては、バラ科モモ属のPrunus Persica Batschの葉の抽出物が特に好ましく例示できる。このうち、芍薬、セイヨウシロヤナギは、有効成分を指標に濃縮し効果を高めることが出来るため特に好ましい。 As the turmeric, the extract of the rhizome of Curcuma domestica Val. Of the ginger family, as the glaze, the extract of the root of Paeonia of the department of the button family, As the licorice, an extract of the root of Glycyrrhiza of the leguminous licorice genus is particularly preferable, and as the peach, an extract of the leaves of Prunus Persica Batsch of the genus Rosaceae is preferable. Of these, glaze and white willow are particularly preferred because they can be concentrated using the active ingredient as an index to enhance the effect.
本発明の皮膚外用剤全量に対し、ヒートショックプロテイン産生促進成分は、0.0001質量%〜10質量%、より好ましくは、0.001質量%〜5質量%、さらに好ましくは、0.015質量%〜3質量%含有することが好ましい。これは、下限未満では本発明の皮膚外用剤が有する肌状態の改善効果が発揮されず、上限を超えると効果が頭打ちになり、色や臭い等の問題が生じ、皮膚外用剤として使用する場合、自由度を損なう場合が存するためである。 The heat shock protein production promoting component is 0.0001% by mass to 10% by mass, more preferably 0.001% by mass to 5% by mass, and still more preferably 0.015% by mass with respect to the total amount of the external preparation for skin of the present invention. % To 3% by mass is preferable. If this is less than the lower limit, the skin condition improvement effect of the external preparation for skin of the present invention is not exhibited, and if the upper limit is exceeded, the effect reaches its peak, causing problems such as color and odor, and when used as an external preparation for skin This is because the degree of freedom may be lost.
(2)本発明の皮膚外用剤の必須成分であるオリゴマーエステル
本発明の皮膚外用剤はその必須成分として、二価カルボン酸1種又は2種以上と水酸基価から算出した平均重合度が2〜15のポリグリセリンとのオリゴマーエステル(以下、オリゴマーエステル)を含有する。二価のカルボン酸としては、特に限定されないが、オリゴマーエステルを含有する皮膚外用剤が使用感に優れることから、炭素数6〜22の直鎖、分岐鎖、若しくは環状構造を含む二価カルボン酸であることが好ましい。これらの二価カルボン酸としては、アジピン酸、ピメリン酸、スベリン酸、アゼライン酸、セバシン酸、2,4−ジエチルペンタン二酸、ウンデカン二酸、ドデカン二酸、トリデカン二酸、テトラデカン二酸、ペンタデカン二酸、ヘキサデカン二酸、オクタデカン二酸、8−エチルオクタデカン二酸、エイコサン二酸、ジメチルエイコサン二酸、シクロヘキサンジカルボン酸等を例示することができる。本発明のオリゴマーエステルは単独の二価カルボン酸でも2種以上の混合された二価カルボン酸から形成されていても良い。
(2) Oligomer ester which is an essential component of the skin external preparation of the present invention The skin external preparation of the present invention has, as its essential component, an average polymerization degree calculated from one or more divalent carboxylic acids and two or more hydroxyl values. 15 oligomer ester with polyglycerin (hereinafter referred to as oligomer ester). Although it does not specifically limit as bivalent carboxylic acid, Since the skin external preparation containing oligomer ester is excellent in a usability | use_condition, C6-C22 linear, branched, or cyclic structure containing divalent carboxylic acid It is preferable that These dicarboxylic acids include adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, 2,4-diethylpentanedioic acid, undecanedioic acid, dodecanedioic acid, tridecanedioic acid, tetradecanedioic acid, pentadecane. Examples include diacid, hexadecanedioic acid, octadecanedioic acid, 8-ethyloctadecanedioic acid, eicosane diacid, dimethyleicosane diacid, cyclohexanedicarboxylic acid, and the like. The oligomer ester of the present invention may be a single divalent carboxylic acid or may be formed from two or more mixed divalent carboxylic acids.
本発明の皮膚外用剤の必須成分であるオリゴマーエステルは、例えば、特開2007−137847号公報記載の方法により調製することが可能であるが、市販品も存在するので、かかる市販品を入手して使用することもできる。このような市販品としては、具体的には、「Neosolue-AquaS」(日本精化株式会社製)が好適に例示される。 The oligomer ester, which is an essential component of the external preparation for skin of the present invention, can be prepared, for example, by the method described in JP-A-2007-137847, but there are also commercially available products. Can also be used. As such a commercial item, specifically, “Neosolue-AquaS” (manufactured by Nippon Seika Co., Ltd.) is preferably exemplified.
本発明の皮膚外用剤におけるオリゴマーエステルの含有量は、皮膚外用剤全量に対して、0.01〜4.0質量%であることが好ましく、0.05〜3.0質量%であることがより好ましい。下限値以下では、ヒートショックプロテイン産生促進成分が十分皮膚に浸透せず効果を発揮しない場合があり、上限値以上では皮膚外用剤の使用感が低下したり、長期保存によりオリゴマーエステルが析出する等の場合があり好ましくない。 The content of the oligomer ester in the external preparation for skin of the present invention is preferably 0.01 to 4.0% by mass, and preferably 0.05 to 3.0% by mass with respect to the total amount of the external preparation for skin. More preferred. Below the lower limit, heat shock protein production-promoting components may not sufficiently penetrate the skin and may not be effective. Above the upper limit, the feeling of use of the external preparation for the skin may decrease, or oligomer esters may precipitate due to long-term storage, etc. This is not preferable.
(3)本発明の皮膚外用剤の必須成分であるグリセリン及びポリグリセリン
本発明の皮膚外用剤はその必須成分として、グリセリン、平均重合度2〜4のポリグリセリンからなる群から選択される一種又二種以上を含有する。それらの内でも、オリゴマーエステルの水への溶解性を向上させる点から、グリセリン、ジグリセリンが好ましい。
(3) Glycerin and polyglycerin as essential components of the external preparation for skin of the present invention The external skin preparation of the present invention is a kind selected from the group consisting of glycerin and polyglycerin having an average polymerization degree of 2 to 4 as its essential components. Contains two or more. Among these, glycerin and diglycerin are preferable from the viewpoint of improving the solubility of the oligomer ester in water.
本発明の皮膚外用剤におけるグリセリン、平均重合度2〜4のポリグリセリンからなる群から選択される一種又二種以上の含有量は0.01〜50.0質量%であり、0.1〜40.0質量%であることが好ましい。下限値以下では、ヒートショックプロテイン産生促進成分が十分浸透せず効果が減弱したり、長期の保存でオリゴマーエステルの溶解性が低下する等の場合があり好ましくない。一方、上限値以上では、塗布時の使用感が低下する場合があり好ましくない。 The content of one or more selected from the group consisting of glycerin and polyglycerin having an average degree of polymerization of 2 to 4 in the external preparation for skin of the present invention is 0.01 to 50.0% by mass, It is preferable that it is 40.0 mass%. Below the lower limit, the heat shock protein production-promoting component does not sufficiently permeate and the effect is diminished, and the solubility of the oligomer ester may be reduced by long-term storage. On the other hand, if it is more than the upper limit value, the feeling of use at the time of application may be lowered, which is not preferable.
(4)本発明の皮膚外用剤
本発明の皮膚外用剤は、その必須成分として、ヒートショックプロテイン産生促進成分、二価カルボン酸1種又は2種以上と水酸基価から算出した平均重合度が2〜15のポリグリセリンとのオリゴマーエステル、及びグリセリン、平均重合度2〜4のポリグリセリンからなる群から選択される一種又二種以上を含有することを特徴とする。
(4) External preparation for skin of the present invention The external preparation for skin of the present invention has, as its essential components, an average polymerization degree of 2 calculated from a heat shock protein production promoting component, one or more divalent carboxylic acids and a hydroxyl value. It contains one or two or more kinds selected from the group consisting of oligomer esters with -15 polyglycerol, glycerol and polyglycerol having an average polymerization degree of 2-4.
本発明の皮膚外用剤は、通常、皮膚外用剤に用いられる油剤を実質的に含有しないことを特徴とするが、本発明においては、実質的に含有しないとは、油剤を含有していても、その含有量が、皮膚外用剤全量に対して0.5質量%以下であることを意味する。 The external preparation for skin of the present invention is characterized in that it usually contains substantially no oil used for external preparations for skin. However, in the present invention, it means that it does not contain substantially any oil. This means that the content is 0.5% by mass or less based on the total amount of the external preparation for skin.
また、本発明における油剤とは、具体的には、マカデミアナッツ油、アボガド油、トウモロコシ油、オリーブ油、ナタネ油、ゴマ油、ヒマシ油、サフラワー油、綿実油、ホホバ油、ヤシ油、パーム油、液状ラノリン、硬化ヤシ油、硬化油、モクロウ、硬化ヒマシ油、ミツロウ、キャンデリラロウ、カルナウバロウ、イボタロウ、ラノリン、還元ラノリン、硬質ラノリン、ホホバロウ等のオイル、ワックス類、流動パラフィン、スクワラン、プリスタン、オゾケライト、パラフィン、セレシン、ワセリン、マイクロクリスタリンワックス等の炭化水素類、セチルアルコール、ステアリルアルコール、イソステアリルアルコール、ベヘニルアルコール、オクチルドデカノール、ミリスチルアルコール、セトステアリルアルコール等の高級アルコール、ラウリン酸、ミリスチン酸、ステアリン酸、ベヘニン酸等の高級脂肪酸、イソオクタン酸セチル、ミリスチン酸イソプロピル、イソステアリン酸ヘキシルデシル、アジピン酸ジイソプロピル、セバチン酸ジ−2−エチルヘキシル、乳酸セチル、リンゴ酸ジイソステアリル、ジ−2−エチルヘキサン酸エチレングリコール、ジカプリン酸ネオペンチルグリコール、ジ−2−ヘプチルウンデカン酸グリセリン、トリ−2−エチルヘキサン酸グリセリン、トリ−2−エチルヘキサン酸トリメチロールプロパン、トリイソステアリン酸トリメチロールプロパン、テトラ−2−エチルヘキサン酸ペンタンエリトリット等の合成エステル油類、脂肪酸セッケン(ラウリン酸ナトリウム、パルミチン酸ナトリウム等)、ラウリル硫酸カリウム、アルキル硫酸トリエタノールアミンエーテル等のアニオン界面活性剤類、塩化ステアリルトリメチルアンモニウム、塩化ベンザルコニウム、ラウリルアミンオキサイド等のカチオン界面活性剤類、イミダゾリン系両性界面活性剤(2−ココイル−2−イミダゾリニウムヒドロキサイド−1−カルボキシエチロキシ2ナトリウム塩等)、ベタイン系界面活性剤(アルキルベタイン、アミドベタイン、スルホベタイン等)、アシルメチルタウリン等の両性界面活性剤類、ソルビタン脂肪酸エステル類(ソルビタンモノステアレート、セスキオレイン酸ソルビタン等)、グリセリン脂肪酸類(モノステアリン酸グリセリン等)、プロピレングリコール脂肪酸エステル類(モノステアリン酸プロピレングリコール等)、硬化ヒマシ油誘導体、グリセリンアルキルエーテル、POEソルビタン脂肪酸エステル類(POEソルビタンモノオレエート、モノステアリン酸ポリオキエチレンソルビタン等)、POEソルビット脂肪酸エステル類(POE−ソルビットモノラウレート等)、POEグリセリン脂肪酸エステル類(POE−グリセリンモノイソステアレート等)、POE脂肪酸エステル類(ポリエチレングリコールモノオレート、POEジステアレート等)、POEアルキルエーテル類(POE2−オクチルドデシルエーテル等)、POEアルキルフェニルエーテル類(POEノニルフェニルエーテル等)、プルロニック型類、POE・POPアルキルエーテル類(POE・POP2−デシルテトラデシルエーテル等)、テトロニック類、POEヒマシ油・硬化ヒマシ油誘導体(POEヒマシ油、POE硬化ヒマシ油等)、ショ糖脂肪酸エステル、アルキルグルコシド等の非イオン界面活性剤類、ジメチコン、フェニルジメチコン、ポリエーテル変性シリコーン、ポリグリセリン変性シリコーン、アミノ変性シリコーン等のシリコーン類、ジエチルアミノヒドロキシベンゾイル安息香酸ヘキシル、t−ブチルメトキシベンゾイルメタン、パラメトキシ桂皮酸2−エチルヘキシル、ジメチコジエチルベンザルマロネート、サリチル酸ホモメンチル、等のUV吸収剤、油溶性ビタミン等が例示される。 Further, the oil agent in the present invention specifically includes macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin. Oils such as hardened coconut oil, hardened oil, mole, hardened castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, waxes, liquid paraffin, squalane, pristane, ozokerite, paraffin , Hydrocarbons such as ceresin, petrolatum and microcrystalline wax, higher alcohols such as cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol Higher fatty acids such as lauric acid, myristic acid, stearic acid, behenic acid, cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, diisostearyl malate , Ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, triisostearic acid tri Synthetic ester oils such as methylolpropane, penta-2-ethylhexanoic acid pentane erythritol, fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, alkyl Anionic surfactants such as acid triethanolamine ether, cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide, imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium) Hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactants (alkyl betaines, amide betaines, sulfobetaines, etc.), amphoteric surfactants such as acylmethyl taurine, sorbitan fatty acid esters (sorbitan monostears) Rate, sorbitan sesquioleate, etc.), glycerin fatty acids (such as glyceryl monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hardened castor oil derivatives, glycerin alkyl Ether, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbite fatty acid esters (POE-sorbite monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerin monoiso) Stearates, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkyl phenyl ethers (POE nonylphenyl ether, etc.), pluronic types, POE / POP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, P E-cured castor oil, etc.), nonionic surfactants such as sucrose fatty acid ester, alkyl glucoside, dimethicone, phenyl dimethicone, polyether-modified silicone, polyglycerin-modified silicone, amino-modified silicone and other silicones, diethylaminohydroxybenzoylbenzoate Examples thereof include UV absorbers such as hexyl acid, t-butylmethoxybenzoylmethane, 2-ethylhexyl paramethoxycinnamate, dimethicodiethylbenzalmalonate, homomenthyl salicylate, and oil-soluble vitamins.
さらに、本発明の皮膚外用剤にはその効果を損なわない範囲において、通常皮膚外用剤で用いられる、油剤以外の任意成分を含有することができる。かかる任意成分としては、例えば、平均分子量2000未満のポリエチレングリコール、平均分子量5000を超えるポリエチレングリコールの多価アルコール類、ピロリドンカルボン酸ナトリウム、乳酸、乳酸ナトリウム等の保湿成分類、グアガム、クインスシード、カラギーナン、ガラクタン、アラビアガム、ペクチン、マンナン、デンプン、キサンタンガム、カードラン、メチルセルロース、ヒドロキシエチルセルロース、カルボキシメチルセルロース、メチルヒドロキシプロピルセルロース、コンドロイチン硫酸、デルマタン硫酸、グリコーゲン、ヘパラン硫酸、ヒアルロン酸、ヒアルロン酸ナトリウム、トラガントガム、ケラタン硫酸、コンドロイチン、ムコイチン硫酸、ヒドロキシエチルグアガム、カルボキシメチルグアガム、デキストラン、ケラト硫酸,ローカストビーンガム,サクシノグルカン,カロニン酸,キチン,キトサン、カルボキシメチルキチン、寒天、ポリビニルアルコール、ポリビニルピロリドン、カルボキシビニルポリマー、ポリアクリル酸ナトリウム、ポリエチレングリコール、ベントナイト等の増粘剤、表面処理されていても良い、マイカ、タルク、カオリン、合成雲母、炭酸カルシウム、炭酸マグネシウム、無水ケイ酸(シリカ)、酸化アルミニウム、硫酸バリウム等の粉体類、表面処理されていても良い、酸化コバルト、群青、紺青、酸化亜鉛の無機顔料類、表面処理されていても良い、酸化鉄二酸化チタン焼結体等の複合顔料、表面処理されていても良い、平均一次粒径が100μm以下の微粒子二酸化チタン、微粒子酸化亜鉛、表面処理されていても良い、雲母チタン、魚燐箔、オキシ塩化ビスマス等のパール剤類、レーキ化されていても良い赤色202号、赤色228号、赤色226号、黄色4号、青色404号、黄色5号、赤色505号、赤色230号、赤色223号、橙色201号、赤色213号、黄色204号、黄色203号、青色1号、緑色201号、紫色201号、赤色204号等の有機色素類、ポリエチレン末、ポリメタクリル酸メチル、ナイロン粉末、オルガノポリシロキサンエラストマー等の有機粉体類、エタノール、イソプロパノール等の低級アルコール類、多価アルコール及び/水で抽出された植物エキス等が例示される。 Furthermore, the external preparation for skin of the present invention can contain optional components other than oils, which are usually used in external preparations for skin, as long as the effects are not impaired. Examples of such optional components include polyethylene glycol having an average molecular weight of less than 2000, polyhydric alcohols of polyethylene glycol having an average molecular weight of more than 5000, moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, guar gum, quince seed, and carrageenan. , Galactan, gum arabic, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, heparan sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, Keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, Thickeners such as kisstran, keratosulfuric acid, locust bean gum, succinoglucan, caronic acid, chitin, chitosan, carboxymethylchitin, agar, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium polyacrylate, polyethylene glycol, bentonite , May be surface-treated, mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, barium sulfate, etc., may be surface-treated, Cobalt oxide, ultramarine, bitumen, zinc oxide inorganic pigments, surface treated, composite pigments such as iron oxide titanium dioxide sintered body, surface treated, average primary particle size of 100 μm or less Fine particle titanium dioxide, fine particle zinc oxide, surface treatment Pearl agents such as titanium mica, fish phosphorous foil, bismuth oxychloride, which may be added, red 202, red 228, red 226, yellow 4, blue 404, yellow, which may be raked Organic dyes such as No. 5, Red No. 505, Red No. 230, Red No. 223, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, Blue No. 1, Green No. 201, Purple No. 201, Red No. 204 Organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer, lower alcohols such as ethanol and isopropanol, polyhydric alcohols and / or plant extracts extracted with water .
本発明の皮膚外用剤は、上記必須成分と任意成分を定法により処理することにより調製することができる。
以下に実施例を挙げて本発明について詳細に説明を加えるが、本発明はかかる実施例にのみ限定されないことは言うまでもない。
The external preparation for skin of the present invention can be prepared by treating the above essential components and optional components by a conventional method.
Hereinafter, the present invention will be described in detail with reference to examples, but it goes without saying that the present invention is not limited to such examples.
表1に示す処方にしたがって本発明の皮膚外用剤を調製した。
表1の成分(イ)を攪拌しながら60℃に加熱した。これに成分(ロ)を常温にて攪拌混合したものを添加し、次に(ハ)を加え攪拌し続け均一溶液とした。次に、成分(ホ)を加え攪拌混合し、均一となるまで攪拌を続け皮膚外用剤を得た。なお表中成分(イ)〜(ホ)における数字は質量%を表す。
According to the formulation shown in Table 1, the external preparation for skin of the present invention was prepared.
Ingredient (a) in Table 1 was heated to 60 ° C. with stirring. To this was added the component (b) stirred and mixed at room temperature, and then (c) was added and stirred continuously to obtain a homogeneous solution. Next, the ingredient (e) was added and stirred and mixed, and stirring was continued until it became uniform to obtain a skin external preparation. In addition, the number in component (I)-(E) in a table | surface represents mass%.
表2に示す処方にしたがって、実施例と同様に比較例の皮膚外用剤を調製した。なお表中成分(イ)〜(ホ)における数字は質量%を表す。 According to the formulation shown in Table 2, the skin external preparation of the comparative example was prepared similarly to the Example. In addition, the number in component (I)-(E) in a table | surface represents the mass%.
<試験例1>
(経皮吸収試験)
フランツ型セルを用いて、ヒートショックプロテイン産生促進成分である芍薬エキスの経皮吸収性を調べた。即ち、隔壁として豚皮を用い、レシーバーにリン酸緩衝生理食塩水(pH7)を充填し、豚皮上に実施例、比較例0.1gを乗せ、37℃で6時間保持し、レシーバー液を採取し、芍薬エキスに含まれるペオニフロリン量を調べた。ペオニフロリン量は日本薬局方のペオニフロリン定量法に従い、232nmにおけるペオニフロリンのピークをODSカラムを用いたHPLC法により測定した。実施例、比較例中のペオニフロリン量、及び経皮吸収試験によりレシーバー液中に移行したペオニフロリン濃度測定し、実施例、比較例中の初期のペオニフロリンの量を各々100とした時のレシーバー中のペオニフロリン量を相対比(%)として算出し表3に示した。
<Test Example 1>
(Transdermal absorption test)
Using a Franz-type cell, the percutaneous absorbability of the glaze extract, which is a heat shock protein production promoting component, was examined. That is, using pig skin as a partition wall, the receiver was filled with phosphate buffered saline (pH 7), and 0.1 g of Examples and Comparative Examples were placed on the pig skin and held at 37 ° C. for 6 hours. The amount of paeoniflorin contained in the glaze extract was examined. The amount of paeoniflorin was measured by the HPLC method using an ODS column at the peak of paeoniflorin at 232 nm according to the Japanese Pharmacopoeia paeoniflorin assay. The amount of paeoniflorin in the examples and comparative examples and the concentration of paeoniflorin transferred into the receiver liquid by the percutaneous absorption test were measured. The amount was calculated as a relative ratio (%) and shown in Table 3.
表3の結果より、実施例ではヒートショックプロテイン産生促進成分である芍薬エキスの吸収量が比較例に比べ高く、ヒートショックプロテイン産生促進成分の透過量が増加していることが明らかとなった。
同様にセイヨウシロヤナギエキスでも同様の結果が確認された。
From the results of Table 3, it was revealed that in the examples, the amount of the glaze extract, which is a heat shock protein production promoting component, was higher than that of the comparative example, and the amount of permeation of the heat shock protein production promoting component was increased.
Similarly, similar results were confirmed with the white willow extract.
<試験例2>
(皮膚損傷予防作用試験)
ヒートショックプロテインの皮膚に対する有用性の一つとして、紫外線照射による障害を低減する作用が知られている。そこで紫外線により損傷を生じた皮膚で観察される日焼け細胞(サンバーンセル:sunburn cell)の出現数を指標として、皮膚損傷予防作用を調べた。
ヒト新鮮皮膚組織(BIOPREDIC International社製)を用意し、皮膚表面に実施例1〜4及び比較例1〜2をそれぞれ皮膚組織表面に1cm²あたり10μlを塗布した。その後、皮膚表面に紫外線(UVB)を100mJ/cm²となるように照射した。組織を10%ホルマリンで固定後、組織切片標本を作製し、ヘマトキシリン・エオジン染色した。組織切片標本の1mm長当りのサンバーンセル数を数え、無塗布部位でのサンバーンセル数を100として実施例及び比較例塗布部位のサンバーンセル出現率(%)を算出し表4に示した。
<Test Example 2>
(Skin injury prevention test)
As one of the usefulness of heat shock protein to the skin, the effect of reducing damage caused by ultraviolet irradiation is known. Therefore sunburn cells observed in the skin caused damage by UV: as (San burn cell sunbur n c ell) index number of occurrences were examined skin damage prevention effect.
Fresh human skin tissue (manufactured by BIOPREDIC International) was prepared, and Examples 1 to 4 and Comparative Examples 1 to 2 were applied to the skin surface at a rate of 10 μl per 1 cm 2 on the skin tissue surface. Thereafter, the skin surface was irradiated with ultraviolet rays (UVB) so as to be 100 mJ / cm <sup2>. After fixing the tissue with 10% formalin, a tissue section specimen was prepared and stained with hematoxylin and eosin. The number of sunburn cells per 1 mm length of the tissue section sample was counted, and the number of sunburn cells at the non-application site was defined as 100. The appearance rate (%) of the sunburn cell at the application site of Examples and Comparative Examples was calculated and shown in Table 4.
表4の結果より、実施例ではサンバーンセルの出現量が比較例に比べて顕著に低く、ヒートショックプロテイン産生促進成分である芍薬エキスにより紫外線照射による皮膚へのダメージを低減する作用が確認された。従って、実施例ではヒートショックプロテイン産生促進成分が皮膚組織中に浸透し、皮膚中のヒートショックプロテインを増やし、サンバーンセルの出現量を低減したことが明らかとなった。同様にセイヨウシロヤナギエキスでも同様のサンバーンセル出現率の低下が確認され、本願実施例が皮膚損傷予防作用を高めることが確認された。 From the results of Table 4, the amount of sunburn cell appeared significantly lower in the examples than in the comparative examples, and the action of reducing damage to the skin caused by ultraviolet irradiation was confirmed by the glaze extract, which is a heat shock protein production promoting component. . Therefore, it was clarified in the Examples that the heat shock protein production promoting component penetrated into the skin tissue, increased the heat shock protein in the skin, and reduced the appearance amount of sunburn cells. Similarly, a similar decrease in the appearance rate of sunburn cells was also confirmed in the white willow extract, and it was confirmed that the examples of the present application enhance the skin damage preventing action.
本発明によれば、肌状態を改善する皮膚外用剤を提供することができる。
ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation which improves a skin state can be provided.
Claims (5)
A)ヒートショックプロテイン産生促進成分として、芍薬及び/又はセイヨウシロヤナギの抽出物
B)二価カルボン酸1種又は2種以上と水酸基価から算出した平均重合度が2〜15のポリグリセリンとのオリゴマーエステル
C)グリセリン、平均重合度2〜4のポリグリセリンからなる群から選択される一種又は2種以上 A skin external preparation containing the following components A, B and C.
A) As a heat shock protein production-promoting component , an extract of glaze and / or white willow B) an oligomer of polyglycerin having an average degree of polymerization of 2 to 15 calculated from one or more divalent carboxylic acids and a hydroxyl value Ester C) Glycerin, one or two or more selected from the group consisting of polyglycerol having an average degree of polymerization of 2 to 4
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