JP6285178B2 - Topical skin preparation - Google Patents

Description

  The present invention relates to an external preparation for skin that has an effect of promoting the penetration of heat shock protein into the skin and improving the skin condition.

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).

However, in order to cope with external environmental stress, skin external preparations containing ingredients that produce heat shock protein or heat shock protein factor have been developed, but these ingredients do not penetrate into the skin sufficiently, and sufficient effects are achieved. However, there has been a demand for a technique that sufficiently permeates the heat shock protein or the component that produces the heat shock protein factor so that the effect can be exhibited.

JP 2004-331602 A JP 2004-238297 A JP 2005-508999 A

  This invention is made | formed in such a condition, and makes it a subject to provide the skin external preparation which fully infiltrates heat shock protein to skin and improves a skin state.

The present inventors have advanced research to provide a skin external preparation capable of improving the skin condition, and surprisingly, average polymerization calculated from heat shock protein, one or more divalent carboxylic acids and a hydroxyl value. A skin external preparation containing an oligomeric ester with polyglycerol having a degree of 2 to 15 and one or more selected from the group consisting of glycerin and polyglycerol having an average degree of polymerization of 2 to 4 is applied to the skin of heat shock protein. Has been found to improve the skin condition by accelerating the penetration of the skin. 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 B) One or two or more divalent carboxylic acids and an oligomeric ester of polyglycerin having an average degree of polymerization calculated from 2 to 15 calculated from the hydroxyl value C) Glycerin, polyglycerin having an average degree of polymerization of 2 to 4 <1> the divalent carboxylic acid selected from the group consisting of <2> 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 the 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 is based on the total amount of the external preparation for skin <1> to <3, characterized in that the skin external preparation <4> is substantially free of oil. > External preparation for skin <> Characterized in that it is a cosmetic <1> to the skin external preparation according to any one of <4>

  Hereinafter, the skin external preparation of the present invention will be described.

(1) Heat shock protein which is an essential component of the external preparation for skin of the present invention The external preparation for skin of the present invention contains heat shock protein as an essential component. Such a heat shock protein is not particularly limited as long as it can be used as a skin external preparation, and specifically, lactic acid bacteria and yeast cultured by a conventional method are treated at 42 to 44 ° C. for 10 to 40 minutes, After increasing the heat shock protein, the culture solution is centrifuged, the precipitate is pulverized, and then the extract extracted with a polar solvent can be used. Moreover, the extract obtained by centrifuging, pulverizing and extracting a culture solution obtained by incorporating a heat shock protein gene into Escherichia coli and culturing it by a conventional method can be used as the heat shock protein. Examples of the polar solvent include water, 1,3-butylene glycol, glycerin, and polypropylene glycol.
A product obtained by drying an extract into a powder, and a product obtained by purifying an extract, a dried product, etc. by partitioning between columns or solutions, and increasing the active ingredient can also be used as a heat shock protein.
Moreover, as a commercial item, Hsp70 (made by Stressgen) and Hsp70 Protein (made by Stress Marq Biosciences Inc.) can be used.

  The heat shock protein 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 to 3%, based on the total amount of the external preparation for skin of the present invention. It is preferable to contain by mass. 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) 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.

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.

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 may not penetrate the skin sufficiently and may not be effective. Above the upper limit, the feeling of use of the external preparation for the skin may decrease, and oligomer esters may precipitate due to long-term storage. It is not preferable.

(3) Glycerin and polyglycerin which are essential components of the skin external preparation of the present invention The skin external preparation of the present invention includes, as its essential components, one kind selected from the group consisting of glycerin and polyglycerin having an average degree of polymerization of 2 to 4. Contains two or more. Among these, glycerin and diglycerin are preferable from the viewpoint of improving the solubility of the oligomer ester in water.

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, 0.1 It is preferable that it is -40.0 mass%. Below the lower limit, the effect of heat shock protein may be 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) External preparation for skin of the present invention The external preparation for skin of the present invention has an average polymerization degree of 2 to 15 calculated from heat shock protein, one or more divalent carboxylic acids and a hydroxyl value as essential components. 1 type or 2 types or more selected from the group which consists of an oligomer ester with polyglycerol, glycerol, and a polyglycerol with an average degree of polymerization 2-4 are characterized by the above-mentioned.

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.

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.

  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 .

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.

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%.

*１）特開２００７−１３７８４７号公報記載の方法により調製

* 1) Prepared by the method described in JP-A-2007-137847

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%.

*１）特開２００７−１３７８４７号公報記載の方法により調製

* 1) Prepared by the method described in JP-A-2007-137847

<Test Example 1>
(Transdermal absorption test)
Using a Franz-type cell, the transdermal absorbability of Examples was examined as a skin external preparation containing Hsp70 as a heat shock protein. Moreover, the percutaneous absorbability was confirmed similarly about the comparative example.
That is, pig skin was used as the partition wall, the receiver was filled with phosphate buffered saline (pH 7), 10 μl of Examples and Comparative Examples were applied on 1 cm ² on the pig skin, and held at 37 ° C. for 6 hours. The liquid was collected and examined for the amount of Hsp70. The amount of Hsp70 was quantified by Western blotting according to a conventional method. Each measured value when the value of Comparative Example 1 was set to 100 was calculated and shown in Table 3.

From the results of Table 3, it was revealed that in the examples, the amount of Hsp70 permeated was larger than that of the comparative example, and the amount of heat shock protein permeated was increased.

<Test Example 2>
(Skin condition confirmation 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 and 2 were each applied to the skin surface at 10 μl per 1 cm ² . 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.

From the results of Table 4, it can be seen that in the examples, the amount of sunburn cell appeared was significantly lower than that in the comparative examples, and the effect of reducing the damage caused by ultraviolet irradiation by the heat shock protein was improved. Therefore, in the examples, it was revealed that heat shock protein penetrated into the skin tissue and reduced the appearance amount of sunburn cells.

ADVANTAGE OF THE INVENTION According to this invention, the skin external preparation which improves a skin state can be provided.

Claims (5)

A skin external preparation containing the following components A, B and C.
A) Hsp70
B) Oligomer ester with polyglycerol having an average polymerization degree of 2 to 15 calculated from one or more divalent carboxylic acids and a hydroxyl value C) Selected from the group consisting of glycerol and polyglycerol having an average polymerization degree of 2 to 4 1 type or 2 types or more The skin external preparation according to claim 1, wherein the divalent carboxylic acid is a divalent carboxylic acid containing a linear, branched or cyclic structure having 6 to 22 carbon atoms. Content of oligomer ester of polyglycerin having an average degree of polymerization of 2 to 15 calculated from one or more divalent carboxylic acids and hydroxyl value is 0.01 to 4.0% by mass with respect to the total amount of skin external preparation. The external preparation for skin according to claim 1 or 2, wherein:   Content of oil agent is 0.5 mass% or less with respect to the said skin external preparation whole quantity, The skin external preparation in any one of Claims 1-3 characterized by the above-mentioned.   It is a cosmetic, The skin external preparation in any one of Claims 1-4 characterized by the above-mentioned.