JP2015189735A - expression inducer of heat shock protein - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel expression inducer more effective than a conventional HSP70 expression inducer.SOLUTION: The present invention relates to an expression inducer of a heat shock protein (HSP) containing ozone-dissolved glycerin. An external preparation containing the expression inducer of the invention can be used as medicines, cosmetics, or the like, particularly, it can be used as medicines or cosmetics for the prevention and treatment of a dermal damage by ultraviolet radiation, inhibition of wrinkle formation by ultraviolet, inhibition of melanogenesis, skin whitening effect, effects of preventing and/or ameliorating stains, and the like.

Description

  The present invention relates to a heat shock protein expression inducer, and more particularly to an expression inducer of the heat shock protein 70 family.

  In cells, tissues, or solids, expression (production) of specific proteins is induced as one of the defense systems of living bodies when exposed to a temperature of 3 ° C. or higher than a general physiological temperature. Are known. This protein exists as a group of proteins having a molecular weight range of 10 to 110 KDa as measured by SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis), and is referred to as heat shock proteins (hereinafter referred to as heat shock proteins). Called "HSP").

  HSP has several families due to the difference in molecular weight. For example, HSP90 family (molecular weight: 90 kDa to 110 kDa), HSP70 family (molecular weight: 70 kDa to less than 80 kDa), HSP60 family (molecular weight: 60 kDa to 70 kDa). Less), and the low molecular weight HSP family (molecular weight: less than 60 kDa).

The functions of HSP are diverse, and many researchers are conducting research from various viewpoints.
So far, the present inventors can obtain an anti-cell death action, an anti-inflammatory action, a cytoprotective action, a gastric mucosa protective action, and the like by inducing the expression of HSP (Patent Document 1), and further protect cells. It has been clarified that it effectively acts on brain diseases such as cerebral infarction and Alzheimer's disease caused by HSP damage and ulcerative colitis (Patent Document 2).

  Furthermore, regarding HSP70, expression of HSP70 prevents skin damage due to ultraviolet irradiation (Non-patent Document 1), suppresses wrinkle formation by ultraviolet light (Non-patent Document 2), and suppresses melanin production. (Patent Documents 1 and 2, Non-Patent Document 3) and the like have been clarified. Further, HSP70 expression inducers were examined (Patent Documents 1 to 4, Non-Patent Documents 4 and 5), and the expression whitening effect (Patent Document 1) and the effect of preventing and improving spots (Patent Document 1) It has been clarified that 3) can be obtained.

  On the other hand, ozone-dissolved glycerin produced by dissolving ozone in high-concentration glycerin has a bactericidal effect and wound healing effect (Patent Documents 5 and 6), moisturizing action (reducing effect of skin moisture transpiration), reducing spots, It has been clarified that it has actions such as improvement of sagging and enhancement of antioxidant function (Patent Documents 7 and 8).

JP 2011-190200 A JP2013-71902A JP 2013-71901 A JP 2008-127296 A JP 2005-232094 A JP 2011-42689 A JP 2007-332078 A JP 2009-1575 A

Matsuda, M. et al., “Prevention of UVB radiation-induced epidermal damage by expression of heat shock protein 70”, J. Biol. Chem. 285, 5848-5858 (2010). Matsuda, M. et al., “Suppression of UV-induced wrinkle formation by induction of HSP70 expression in mice”, J. Invest. Dermatol. 133, 919-928 (2013). Hoshino, T. et al., “Suppression of melanin production by expression of HSP70”, J. Biol. Chem. 285, 13254-13263 (2010). Yamashita, Y. et al., “HSP70 inducers from Chinese herbs and their effect on melanin production”, Experimental Dermatology, 19, e340-e342 (2010) Yamashita, Y. et al., “Purification and characterization of HSP-inducers from Eupatorium lindleyanum”, Biochemical Pharmacology 83, 909-922 (2012).

  Although researches on HSP70 expression inducers have been mainly focused on plants such as extracts derived from herbal medicines, the present inventors have found that the usefulness of HSP70 is expected based on original research and investigation. While thinking that attention should be paid to the expected demand, we came to realize that there is an urgent need to obtain a higher performance expression inducer. That is, an object of the present invention is to provide a new expression inducer that is more effective and economical than conventional HSP70 expression inducers.

  The inventors of the present invention have found that ozone-dissolved glycerin induces the expression of HSP70 very effectively in the course of intensive research to solve such problems, and have further advanced the research to complete the present invention. . That is, the present invention relates to the following.

[1] An expression inducer of heat shock protein (HSP) containing ozone-dissolved glycerin.
[2] The expression inducer according to [1], wherein HSP belongs to the HSP70 family.
[3] The expression inducer according to [1] or [2], wherein the ozone concentration of ozone-dissolved glycerin is 10 ppm to 10,000 ppm.
[4] An external preparation for skin or mucous membrane, containing the expression inducer according to any one of [1] to [3].
[5] The external preparation described in [4] above, which is a lotion, emulsion, gel, cream, ointment or patch.
[6] The external preparation according to the above [4] or [5], which is for pharmaceutical use or cosmetic use.
[7] The external preparation according to any one of [4] to [6], which is an anti-wrinkle agent.
[8] The external preparation according to any one of [4] to [6], which is a whitening agent.
[9] The external preparation according to any one of [4] to [6], which is an ultraviolet protective agent.

  The HSP expression inducer of the present invention can induce HSP expression very effectively. In particular, the expression ability of HSP70 is high, and the conventional expression inducer obtained by screening from 400 kinds of crude drugs has about twice the expression ability compared to the control, whereas the expression inducer of the present invention is a control. The expression ability was about 3 to 3.5 times higher than that of. Since it exhibits such high expression ability, it can be obtained by induction of HSP expression, and it has anti-cell death action, anti-inflammatory action, cytoprotective action, gastric mucosa protective action, and brain such as cerebral infarction and Alzheimer's disease. It can be used as a therapeutic agent for diseases and ulcerative colitis.

Furthermore, the HSP expression inducer of the present invention has a high expression ability of HSP70, which prevents and cures skin damage caused by ultraviolet irradiation, suppresses wrinkle formation by ultraviolet rays, suppresses melanin production, skin whitening effect, and prevents and improves spots. It can be used as a medicine or cosmetic that exhibits effects and the like.
Furthermore, the expression inducer of HSP of the present invention can be produced by a simple production method by using ozone-dissolved glycerin as an active ingredient, compared to an expression inducer containing an extract from a conventional herbal medicine as an active ingredient. It is excellent in mass productivity and economy, and can be stably provided to consumers.

FIG. 1 is a Western blot result (upper row) showing that the ozone cream of the present invention induced HSP expression and a graph (lower row) showing the expression intensity.

The expression inducer of heat shock protein (HSP) of the present invention contains ozone-dissolved glycerin.
The ozone-dissolved glycerin used in the present invention can be produced by gas-liquid contact between a high-concentration glycerin solution and a gas having a high ozone concentration.
As the high-concentration glycerin solution, a glycerin solution having a glycerin concentration of 75% or more can be used, but 84 to 87% by weight of glycerin of the Japanese pharmacopoeia product is preferable, and the glycerin concentration of the Japanese pharmacopoeia product is 98% or more. More preferably, glycerin is used. Further, it is more preferable to use purified glycerin having a concentration of 98.5% or more. When the glycerin concentration is high, ozone can be dissolved at a higher concentration.

A gas having a high ozone concentration can be produced by an ozone generator that generates ozone by silent discharge to oxygen gas, for example. When oxygen gas is used, a medical oxygen cylinder may be used, or oxygen gas produced by an oxygen generator may be used.
As a method for bringing a high-concentration glycerin solution into contact with a gas having a high ozone concentration, for example, a high-concentration (for example, 98% or more) glycerin solution is placed in a tank, and a high concentration of ozone is contained in the tank using an air diffuser. There is a method for releasing gas as fine bubbles. For example, an ozone-dissolved glycerin solution having an ozone concentration of about 3000 ppm can be produced by aeration of a gas having an ozone concentration of 80 g / kL (about 37000 ppm) in concentrated glycerin for about 7 days. By performing aeration for a longer time, an ozone-dissolved glycerin solution having a higher ozone concentration can be produced.

  The HSP that is induced by the expression inducer of the present invention typically belongs to the HSP70 family. The expression inducer of the present invention can also induce expression of HSP32 (HO-1; heme oxygenase-1).

  The ozone concentration of the ozone-soluble glycerin used in the present invention can be appropriately adjusted according to the purpose of inducing the expression of HSP70, and is not particularly limited. The ozone concentration of the ozone-dissolved glycerin is typically 10 ppm to 10000 ppm, and preferably 500 ppm to 10000 ppm.

The HSP expression inducer of the present invention can be in various dosage forms to which glycerin can be administered. For example, it can be an internal medicine, an orally administered drug, etc., but it can typically be an external preparation used for the skin or mucous membrane. Although the aspect of the external preparation of the present invention is not particularly limited, it can be a lotion, emulsion, gel, cream, ointment, pack, tape or patch.
The external preparation of the present invention can be used as a pharmaceutical, quasi-drug or cosmetic, preferably for pharmaceutical or cosmetic use. When used as a quasi drug or cosmetic, a skin external preparation is preferred.
Among the external preparations of the present invention, those used as medicines or quasi drugs may contain various pharmaceutical ingredients or ingredients used in quasi drugs in addition to the ozone-dissolved glycerin solution.

Further, among the external preparations of the present invention, those used as cosmetics, in addition to the ozone-dissolved glycerin solution, increase the cleanliness, beautification, attractiveness, change the appearance of the human body, or healthy the skin, mucous membrane or hair. Ingredients for keeping may be included.
When the HSP expression inducer of the present invention is used as a cosmetic, specifically, skin cosmetics such as lotion, milky lotion, cream, cosmetic liquid, pack, cleansing, facial cleanser, UV protection agent, makeup base lotion, Makeup base creams and other foundation cosmetics, emulsions, oils, solids, and other types of foundations, eye and teak color makeup cosmetics, hand creams, leg creams, neck creams, body lotions, etc. It may be a body cosmetic.

The medicine containing the expression inducer of the present invention is a medicine using an anti-cell death action, an anti-inflammatory action, a cytoprotective action, a gastric mucosa protective action, and a treatment for brain diseases such as cerebral infarction and Alzheimer's disease and ulcerative colitis It can be used for medicine.
The external preparation of the present invention is further used as a medicine or a cosmetic that exhibits prevention and healing of skin damage caused by ultraviolet irradiation, suppression of wrinkle formation by ultraviolet irradiation, suppression of melanin production, skin whitening effect, spot prevention / amelioration effect, etc. can do.
Therefore, the external preparation of the present invention can be used as an anti-wrinkle agent, a whitening agent (anti-stain agent), an ultraviolet protective agent for protecting the skin from ultraviolet rays, and the like.

  The concentration of glycerin in the external preparation of the present invention is usually preferably 20% or less. By making the concentration of glycerin 20% or less, it is possible to suppress irritation of glycerin to the skin or mucous membrane. Therefore, an appropriate diluent can be mixed and diluted with the ozone-dissolved glycerin solution. As the diluent, those which are not easily degraded by ozone are suitable, and water, polyethylene glycol and the like are suitable.

  On the other hand, by making the glycerin concentration 50% or more of the high concentration, a warming effect can be exerted, and the irritability of the high concentration of glycerin can be avoided by washing away after a certain time. . Furthermore, the oxidation reaction by ozone can be stopped by washing away. At this time, it is preferable to use an antioxidant or alkaline water because the oxidation reaction by ozone is more rapidly stopped. In particular, if an antioxidant is used, the antioxidant consumed in the skin can be replenished. When vitamin C or vitamin E is applied in advance, when the external preparation of the present invention is applied, ozone is decomposed, but conversely, after using the external preparation of the present invention, an antioxidant is administered. For example, in combination with the predetermined effect of the external preparation of the present invention, there is an effect that the reaction of ozone is stopped and the lost antioxidant substance can be replenished.

  When water is used as a diluent, it is preferable to use pure water or ultrapure water. By using pure water or ultrapure water, it is possible to suppress the generation of oxides (peroxides) that can be oxidized to ozone and cause irritation to the skin or mucous membrane by impurities or a reduction in the expression of effects. As water, it is more preferable to use water having an acidic pH, that is, acidic water having a pH of less than 7.

  Polyethylene glycol may be used as the diluent. Polyethylene glycol is liquid or solid depending on the molecular weight, and any of them can be used in the present invention. By changing the mixing ratio of two or more types of polyethylene glycol according to the texture at the time of use, it is possible to obtain a texture that is easier to use. Accordingly, the type of polyethylene glycol is not particularly limited, but polyethylene glycol 450 and polyethylene glycol 65M are preferable, and a combination of these is more preferable.

  As an additional component used suitably for the external preparation of this invention, water, at least 1 sort (s) of a moisturizer, a thickener, and antiseptic | preservative are mentioned. The external preparation of the present invention containing all these additional components is preferred.

(water)
In the external preparation of the present invention, water is used, for example, for moisturizing or diluting glycerin, and the type thereof is not particularly limited. It is preferable to use acidic water as water because ozone is more suitably stored. The use of acidic soft water prepared using an H-type cation exchange resin is particularly preferred because it can also exhibit an astringent effect and an effect of improving pore opening due to convergence.
As water, pure water or ultrapure water is also preferable as described above. Therefore, acidic pure water is particularly preferable. In addition, by using neutral or acidic water obtained by electrolyzing water, it is possible to further improve the penetration into the skin. Furthermore, acidic water is preferable in that decomposition of ozone is suppressed.

  The amount of water in the external preparation is not limited, and can be appropriately modified within the range of 0 to 99% of the total external preparation for the purpose of relaxing or moisturizing the viscosity of the external preparation of the present invention resulting from glycerin.

(Humectant)
In the external preparation of the present invention, the humectant is used for moisturizing the skin and mucous membrane, and the type thereof is not particularly limited. Any humectant can be used as long as it has a moisturizing action. These components include polyhydric alcohols, NMF (natural moisturizing factor) including PCA-Na (sodium pyrrolidonecarboxylate), hyaluronic acid, acetyl hyaluronic acid Na and derivatives thereof, or salts thereof (sodium salt, potassium salt). Etc.), polysaccharides, polymer agents (thickeners) and the like. The blending amount of the humectant in the external preparation is preferably 0.1 to 1% of the entire external preparation.

  As the humectant, polyhydric alcohols, NMF (natural moisturizing factor) such as PCA-Na, and hyaluronic acid derivatives such as sodium hyaluronate and salts thereof are preferable. Polyethylene glycol is preferable as the polyhydric alcohol, and one or more of them can be used in combination. Polyethylene glycol is preferably polyethylene glycol 450 and polyethylene glycol 65M, and a combination of these is more preferable.

(Thickener)
In the external preparation of the present invention, the thickener is used for adjusting the viscosity of the agent, and the type thereof is not particularly limited. As the thickener, a water-soluble or water-swellable polymer compound is preferable, xanthan gum, gelatin, pectin, agarose, alginate, dextrin, methylcellulose, ethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, Examples thereof include a natural polymer such as a maleic anhydride copolymer, polyacrylic acid and a salt thereof, or a crosslinked product thereof, or a modified product thereof, or a synthetic polymer or a crosslinked product thereof. These polymers may be used alone or in combination of a plurality of polymers. Xanthan gum is most preferred.
Although there is no restriction | limiting in particular as long as the content with respect to the whole external preparation of these thickeners can provide moderate viscosity to an external preparation, 0.1 to 1% of the whole external preparation is preferable.

(Preservative)
In the external preparation of the present invention, the preservative is used for keeping the external preparation clean, and the kind thereof is not particularly limited. Preservatives include phenoxyethanol, paraoxybenzoic acid esters (parabens), benzoic acid, salicylic acid and its salts, sorbic acid and its salts, dehydroacetic acid and its salts, chlorcresol, hexachlorophene, resorcin, paraoxyenoxacin, Profloxacin, nalidix, norfloxacin, fleroxacin, ofloxacin. Examples include isopropylmethylphenol, orthophenylphenol, chlorhexidine hydrochloride, chlorhexidine gluconate, alkylisoquinolium bromide, trichlorocarbanide, halocarban, photosensitizer 201, triclosan, grape seed extract, benzalkonium hydrochloride, phenol, thymol It is done. Phenoxyethanol is most preferred.
The content of these preservatives with respect to the entire external preparation is not particularly limited as long as the external preparation can be kept clean, but is preferably 0.01 to 1% of the entire external preparation.

  In the external preparation of the present invention, at least one surfactant, anti-inflammatory agent and ceramide or a precursor thereof can also be used. The external preparation of the present invention containing at least one surfactant, anti-inflammatory agent and ceramide or a precursor thereof is preferred.

(Surfactant)
The surfactant is used for dissolving substances that are not mixed with each other in the agent of various components, and the type thereof is not particularly limited.
Surfactants include nonionic surfactants such as sodium lauroyl sulfate and polyoxyethylene sorbitan monooleate, anionic surfactants such as alkyl sulfate salts and sodium normal dodecylbenzene sulfonate, polyoxyethylene dodecyl monomethyl ammonium chloride And a cationic surfactant. Most preferred is sodium lauroyl sulfate.
The content of these surfactants with respect to the entire external preparation is not particularly limited as long as sufficient solubility can be imparted to each component.

(Anti-inflammatory agent)
Anti-inflammatory agents are used to more effectively suppress inflammation of the skin or mucous membrane, and the type thereof is not particularly limited.
Examples of the anti-inflammatory agent include various steroidal anti-inflammatory agents and non-steroidal agents such as glycyrrhizic acid or a salt thereof, allantoin, or ougon extract. Of these, glycyrrhizic acid and glycyrrhizic acid 2K are preferred, and glycyrrhizic acid 2K is particularly preferred.
There is no restriction | limiting in particular as long as the content with respect to the whole external preparation of these anti-inflammatory agents can suppress inflammation effectively.

(Ceramide or its precursor)
Ceramide and its precursor are the main components that occupy about half of the lipids that fill the gaps between cells in the stratum corneum and connect them together, and they contain abundant moisture and work to prevent the moisture from evaporating. It has the effect of preventing external stimuli and bacteria from entering.
Examples of ceramide or a precursor thereof include ceramide 1, ceramide 2, ceramide 3, ceramide 6II and phytosphingosine, cholesterol and the like, and those containing all of ceramide 1, ceramide 3, ceramide 6II, phytosphingosine and cholesterol are preferable.
There is no restriction | limiting in particular as long as the content with respect to the whole external preparation of these ceramides or its precursor can have a moisturizing effect and / or an antimicrobial effect.

  The external preparation of the present invention is used in combination with an antioxidant and a neutralizing agent for the purpose of reducing or stopping the oxidative action of ozone on the skin by a prescription-free pharmaceutical, quasi-drug, and cosmetics. be able to. In this case, after using the external preparation described in the present method produced from ozone-dissolved glycerin, by administering an antioxidant, the reaction of ozone is stopped in combination with the predetermined effect, and the lost antioxidant It is preferable because the effect that it can be replenished can be obtained.

Antioxidants / neutralizing agents are not limited but include, for example:
・ Vitamin Cs, vitamin Es, vitamins such as selenium,
・ Plant-derived substances such as flavonoids,
・ Carotenoids (α-carotene, β-carotene, γ-carotene), plant-derived antioxidants (SOD-like substances) such as lycopene, xanthophyll, astaxanthin, etc. ・ Terpenes such as flavonoids, ubiquinone, saponin, inositol, catechin, tannin, anthocyanin , Isoflavones,
-Plant-derived polyphenols such as grape seeds, ginkgo biloba leaves, coastal pine bark (Pycnogenol),
-Glutathione, diisopropanolamine, diethanolamine (DEA), triisopropanolamine, triethanolamine (TEA), fullerene (C60).

Of the antioxidants and neutralizing agents, vitamin Cs, vitamin Es, polyphenols, glutathione and fullerene are preferable, and vitamins C, vitamin E, glutathione and fullerene are particularly preferable.
The content of the antioxidant / neutralizing agent with respect to the entire external preparation is not particularly limited as long as the pH of the external preparation can be suitably maintained.

In the external preparation of the present invention, ethanol or aroma oil can also be suitably used as a cooling agent. Aroma oils include lavender, orange, grapefruit, sandalwood, ylang ylang, peppermint, lemongrass, chamomile roman, rose, rosemary and the like, with lavender oil and rose oil being preferred.
The stability of these components in the external preparation of the present invention is significantly better than in air or water. Therefore, the external preparation of the present invention containing ethanol or aroma oil is preferable because it can provide a longer cooling effect due to these components.

The content of ethanol or aroma oil with respect to the entire external preparation is not particularly limited as long as the desired effect is exhibited.
The external preparation of the present invention can contain auxiliary components acceptable to the skin or mucous membrane. Such an auxiliary component is, for example, a stabilizer such as EDTA, paraoxybenzoic acid ester or the like, and the amount thereof is not limited as long as it does not impair the effect of the external preparation of the present invention.

  EXAMPLES Hereinafter, although this invention is demonstrated in detail using an Example, this invention is not limited to these Examples.

[Example 1] Preparation of ozone-dissolved glycerin (ozone gel) Concentrated glycerin and ozone were brought into gas-liquid contact to produce an ozone-dissolved glycerin solution (ozone gel). Here, the concentrated glycerin means glycerin having a concentration of 98% or more of Japanese Pharmacopoeia.
A Teflon (registered trademark) tank having a capacity of 50 L was used as the contact tank. A diffuser tube was installed on the bottom of the tank so that ozone could be supplied into the tank as fine bubbles. As the ozone generator, a silent discharge type ozone generator having an ozone generation capacity of 100 g / h using oxygen having a concentration of 90% or more as a raw material was used.
Put 22kg of concentrated glycerin into the tank, send 20L of oxygen per minute into the ozone generator, release the gas containing the generated ozone from the diffuser into the tank for 7 days, and the ozone dissolved glycerin solution with a final concentration of 3000ppm ozone concentration Got.
According to the purpose of use, an ozone gel having an ozone concentration adjusted was obtained by appropriately diluting with water or a diluent (eg, polyethylene glycol).

[Example 2] Preparation of ozone cream PEG450 and PEG65M were mixed in advance, ozone-dissolved glycerin (ozone concentration 2000 ppm) was added to the mixture, and the mixture was slowly stirred with a homogenizer to obtain an ozone cream.

[Example 3] Evaluation of ability to induce HSP70 with ozone cream On the back skin of 8-week-old female hairless mouse HOS: HR-1 (obtained from Hoshi Test Animal Breeding), 1 mg of ozone cream (ozone concentration 2000 ppm) ) And the back skin was collected 3 hours or 6 hours after application.
The expression of HSP70 was confirmed by Western blotting. As a loading control, actin expression was confirmed. Western blotting was performed according to the following procedure.

<Western blot method>
The collected dorsal skin was crushed and RIPA buffer solution supplemented with protease inhibitor mix (hereinafter referred to as PI Mix) [50 mM Tris-HCl (pH 7.2), 150 mM NaCl, 1% NP-40, 1% Sodium, deoxycolate, 0.05 % SDS], centrifuged (15000 rpm, 4 ° C., 10 minutes), and the supernatant was used as a sample in the experiment.
The amount of protein in each sample was determined using a Bio-Rad protein assay kit (Bradford method: Bio Rad), and the amount of protein was adjusted to the same amount before use in the experiment.
The sample was subjected to SDS-PAGE using polyacrylamide and transferred to a PVDF membrane. Then, immunoblotting was performed with primary antibody (against HSP70 (R & D system, catalog number MAB1663), Actin Antibody (I-19) (Santa Cruz Biotechnology, Inc.), 1: 1000 dilution), and secondary antibody, and SuperSignal The target band was detected by WestDura (chemiluminescence method: Pierce) using LAS-3000 mini.

  It was revealed that the ozone cream of the present invention induces the expression of HSP70 (FIG. 1). Specifically, compared to the control (no treatment), expression of HSP70 could be induced about 2 times or more after 3 hours and about 3.5 times or more after 6 hours. Although this result cannot be directly compared because the experimental system is different, Artemia extract, which is superior among conventional herbal medicine-derived HSP expression inducers, increased about 25% compared to the control 24 hours after application, In other words, taking into account that it is about 1.25 times, it can be said that strong expression induction was achieved in a very short time.

Therefore, the HSP expression inducer of the present invention can effectively induce the expression of HSP70 in a small amount of pharmaceutical, quasi-drug or cosmetic.
Furthermore, it was revealed that the ozone cream of the present invention also induces the expression of HO-1 (HSP32) (data not shown). Therefore, the HSP expression inducer of the present invention can induce the expression of HSP70 and HSP32.

  The HSP expression inducer of the present invention is useful in a wide range of fields such as pharmaceuticals, quasi drugs or cosmetics. In particular, in order to induce the expression of HSP70 very effectively, it is useful as a medicine, quasi-drug or cosmetic in terms of the effects related to HSP70.

Claims (9)

  An expression inducer of heat shock protein (HSP) containing ozone-dissolved glycerin.   The expression inducer according to claim 1, wherein the HSP belongs to the HSP70 family.   The expression inducer according to claim 1 or 2, wherein the ozone concentration of the ozone-dissolved glycerin is 10 ppm to 10,000 ppm.   The external preparation used for the skin or mucous membrane containing the expression inducer as described in any one of Claims 1-3.   The external preparation according to claim 4, which is a lotion, emulsion, gel, cream, ointment or patch.   The external preparation according to claim 4 or 5, which is for pharmaceutical use or cosmetic use.   The external preparation according to any one of claims 4 to 6, which is an anti-wrinkle agent.   The external preparation according to any one of claims 4 to 6, which is a whitening agent.   The external preparation according to any one of claims 4 to 6, which is an ultraviolet protective agent.