Agent for reducing hypersensitivity

Abstract

To provide an agent for reducing hypersensitivity in the skin, the agent being capable of reducing or alleviating the level of hypersensitive-type sensitive skin that is apparently healthy skin.SOLUTION: The present invention relates to an agent for reducing hypersensitivity in the skin, the agent containing (A) γ-amino-β-hydroxybutyric acid as an active ingredient.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a hypersensitivity reducing agent.

Background Art

[0002] In recent years, the term "sensitive skin" has become commonly used and is often covered in women's magazines and the like. When asking people who perceive themselves to have sensitive skin about their symptoms, specific symptoms include "tingling when using cosmetics", "stinging and itching", "acne and eruptions are likely to occur", and "becoming red immediately with a weak stimulus". Analyzing people who perceive themselves to have sensitive skin, for example, they are classified into three types: I. a type with a collapsed epidermal barrier, II. an inflammatory type, and III. a hypersensitive type that appears to be healthy skin. Regarding these three types, in order to improve sensitive skin and restore healthy skin, appropriate care for each type was considered necessary. The reason is that the causes of sensitive skin are different for each type. Among the three types, it was found that for type I, using niacinamide having an epidermal lipid synthesis activation effect can improve the barrier function and also improve the resistance to stimuli. However, for types II and III, since the causes of sensitive skin are different from those of type I, no improvement was seen with that method. For types II and III, for example, in past preliminary experiments, it was found that treating with a plant-derived component having an NGF (nerve growth factor) inhibitory effect tends to relieve hypersensitivity, but there was still room for further study (Non-Patent Document 1).

[0003] On the other hand, γ-amino-β-hydroxybutyric acid is used by being formulated in cosmetics and the like, and is known to have an effect of preventing skin aging and a whitening effect (for example, Patent Documents 1 to 3).

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Summary of the Invention

Problems to be Solved by the Invention

[0006] Among sensitive skin types, in particular, for the hypersensitive type of sensitive skin that appears to be healthy, there has been a demand for an external preparation that reduces and alleviates its degree.

Means for Solving the Problems

[0007] The present inventor has found that γ-amino-β-hydroxybutyric acid has an effect of reducing and alleviating the degree of hypersensitivity in the hypersensitive type of sensitive skin that appears to be healthy, and that γ-amino-β-hydroxybutyric acid is useful as a skin hypersensitivity reducing agent, thereby completing the present invention.

[0008] The present invention relates to a skin hypersensitivity reducing agent containing (A) γ-amino-β-hydroxybutyric acid as an active ingredient.

Effects of the Invention

[0009] The hypersensitivity reducing agent of the present invention can reduce and alleviate the degree of hypersensitivity in the hypersensitive type of sensitive skin that appears to be healthy.

Brief Description of the Drawings

[0010]

Figure 1

Mode for Carrying Out the Invention

[0011] The terms used in this specification are used in the meanings commonly used in the art, unless otherwise specified.

[0012] In this specification, skin hypersensitivity refers to sensitive skin as described above, that is, skin that does not have obvious inflammation but causes sensations such as tingling, stinging, and prickling. The skin hypersensitivity reducing agent of the present invention is effective for all such sensitive skin in general, but is particularly effective for the hypersensitive type of sensitive skin that appears to be healthy skin (type III described above). In addition, a skin hypersensitivity reducing agent refers to reducing or alleviating the degree of hypersensitivity.

[0013] γ-Amino-β-hydroxybutyric acid of component (A) is a known substance and has the following chemical properties.

[0014] [Chemical Formula 1] · Chemical name: γ-Amino-β-hydroxybutyric acid (γ-amino-β-hydroxy butyric acid) · Molecular formula: C4H9NO3 · Molecular weight: 119.12 · Melting point: 205 - 210 °C · Structural formula: H2N-CH2-CH-CH2COOH | OH

[0015] The content of component (A) is preferably 0.005% by mass or more, more preferably 0.05% by mass or more, still more preferably 0.3% by mass or more, preferably 2% by mass or less, more preferably 1.5% by mass or less, and still more preferably 1% by mass or less in the total composition from the viewpoints of reducing and alleviating the degree for the hypersensitive type of sensitive skin that appears to be healthy skin and reducing the stickiness during application. Further, the content of component (A) is preferably 0.005% by mass or more and 2% by mass or less, more preferably 0.05% by mass or more and 1.5% by mass or less, and still more preferably 0.3% by mass or more and 1% by mass or less in the total composition.

[0016] The hypersensitivity reducing agent of the present invention can further contain (B) polyhydric alcohol, and can reduce and alleviate the degree for the hypersensitive type of sensitive skin that appears to be healthy skin and reduce the stickiness after application. It should be noted that component (B) does not include component (D) osmolyte described later. The polyhydric alcohol is a compound having two or more hydroxyl groups in the molecule, and any one can be used as long as it is used in a normal external preparation for skin. Examples of the dihydric alcohol include polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, 1,3-butylene glycol, propanediol and the like. Examples of the trihydric alcohol include glycerin, trimethylolpropane and the like. Examples of the tetrahydric alcohol include diglycerin, erythritol and the like. Examples of the polyhydric alcohol having a valence of 5 or more include polyglycerins such as triglycerin; saccharides and sugar alcohols such as glucose, maltose, maltitol, sucrose, xylitol, sorbitol, maltvitol, polyoxyethylene methyl glucoside, polyoxyethylene ethyl glucoside, polyoxyethylene propylene glucoside.

[0017] As the polyhydric alcohol, from the viewpoints of reducing and alleviating the degree and reducing the stickiness during application for sensitive skin of the hypersensitive type that appears to be healthy skin, it preferably contains one or more selected from dihydric alcohols, trihydric alcohols, tetrahydric alcohols, and sugar alcohols, more preferably contains one or more selected from dihydric alcohols, trihydric alcohols, and tetrahydric alcohols, still more preferably contains one or more selected from trihydric alcohols and tetrahydric alcohols, and even more preferably contains one or more selected from glycerin and diglycerin.

[0018] The polyhydric alcohol of component (B) can be used in combination of one or more, and the content is preferably 1% by mass or more in the whole composition, more preferably 3% by mass or more, still more preferably 5% by mass or more, preferably 20% by mass or less, more preferably 15% by mass or less, and still more preferably 12% by mass or less, from the viewpoints of reducing and alleviating the degree, reducing the stickiness during application, and improving the moisturizing feeling for sensitive skin of the hypersensitive type that appears to be healthy skin. Also, the content of component (B) is preferably 1% by mass or more and 20% by mass or less in the whole composition, more preferably 3% by mass or more and 15% by mass or less, and still more preferably 5% by mass or more and 12% by mass or less.

[0019] The hypersensitivity reducing agent of the present invention can further contain (C) a pH adjuster, which can reduce and alleviate the degree and improve the stability of the preparation for sensitive skin of the hypersensitive type that appears to be healthy skin. Note that component (C) does not include component (D) the osmolyte described later. As the pH adjuster, any can be used as long as it is used in ordinary external skin preparations, and inorganic acids and their salts, organic acids having 6 or less carbon atoms and their salts are preferable, and organic acids having 6 or less carbon atoms and their salts are more preferable. As the inorganic acid, for example, it preferably contains one or more selected from hydrochloric acid, nitric acid, nitrous acid, sulfuric acid, sulfurous acid, phosphoric acid, phosphonic acid, phosphinic acid, and their salts, and more preferably contains one or more selected from phosphoric acid and their salts. In addition, as the organic acids having 6 or less carbon atoms and their salts, water-soluble organic acids and their salts are preferred. For example, fatty acids, hydroxy acids, dicarboxylic acids having 1 to 6 carbon atoms, and their salts, etc. may be mentioned. Among these, it is preferable to contain one or more selected from malic acid, lactic acid, citric acid, succinic acid, acetic acid, tartaric acid, aspartic acid, adipic acid and their salts, more preferably to contain one or more selected from malic acid, lactic acid, citric acid, succinic acid and their salts, and even more preferably to contain one or more selected from citric acid and its salts.

[0020] The pH adjuster of component (C) can be used in combination of one or more kinds. The content is preferably 0.01% by mass or more in the total composition from the viewpoints of reducing and alleviating the degree for the hypersensitive type of sensitive skin that appears to be healthy skin, improving the stability of the preparation, and obtaining pH buffering ability, more preferably 0.03% by mass or more, even more preferably 0.05% by mass or more, preferably 1% by mass or less, more preferably 0.5% by mass or less, and even more preferably 0.3% by mass or less. In addition, the content of component (C) is preferably 0.01% by mass or more and 1% by mass or less in the total composition, more preferably 0.03% by mass or more and 0.5% by mass or less, and even more preferably 0.05% by mass or more and 0.3% by mass or less.

[0021] The hypersensitivity reducing agent of the present invention can further contain (D) an osmolyte, and can reduce and alleviate the degree for the hypersensitive type of sensitive skin that appears to be healthy skin, and can reduce the stickiness after application. Note that component (D) does not include component (B) polyhydric alcohol and component (C) pH adjuster. Examples of the osmolyte include ectoine, sodium pyrrolidonecarboxylate (PCA-Na), arginine, arginine hydrochloride, carnitine chloride, taurine, glutamic acid, glutamate, serine, N-methyl-L-serine, trimethylglycine, alanine, etc. As the osmolite, from the viewpoints of reducing and alleviating the degree of sensitivity and reducing stickiness during application for hypersensitive type sensitive skin that appears to be healthy skin, it preferably contains one or more selected from ectoin, sodium pyrrolidone carboxylate (PCA-Na), arginine, N-methyl-L-serine, and alanine, more preferably contains one or more selected from ectoin, sodium pyrrolidone carboxylate (PCA-Na), and N-methyl-L-serine, and even more preferably contains sodium pyrrolidone carboxylate (PCA-Na).

[0022] The osmolite of component (D) can be used in combination of one or more kinds. The content is preferably 0.015% by mass or more in the total composition, more preferably 0.02% by mass or more, even more preferably 0.5% by mass or more, preferably 3.5% by mass or less, more preferably 3% by mass or less, and even more preferably 2% by mass or less, from the viewpoints of reducing and alleviating the degree of sensitivity and reducing stickiness during application for hypersensitive type sensitive skin that appears to be healthy skin. Also, the content of component (D) is preferably 0.015% by mass or more and 3.5% by mass or less in the total composition, more preferably 0.02% by mass or more and 3% by mass or less, and even more preferably 0.5% by mass or more and 2% by mass or less.

[0023] In the present invention, the water content is preferably 20% by mass or more in the total composition, more preferably 40% by mass or more, even more preferably 60% by mass or more, preferably 98.975% by mass or less, more preferably 90% by mass or less, and even more preferably 85% by mass or less, from the viewpoint of uniformly dissolving components (A) and (D) and reducing stickiness during application. Also, the water content is preferably 20% by mass or more and 98.975% by mass or less in the total composition, more preferably 40% by mass or more and 90% by mass or less, and even more preferably 60% by mass or more and 85% by mass or less.

[0024] In addition to the above components, the topical skin preparation of the present invention can contain components used in ordinary topical skin preparations, such as oily components, surfactants, preservatives, antioxidants, pigments, fragrances, plant extracts, colorants, powders, ultraviolet absorbers, humectants other than component (B), blood circulation promoters, cooling agents, antiperspirants, bactericides, skin activators, and the like.

[0025] The hypersensitivity reducing agent of the present invention can be produced according to a conventional method. For example, it can be produced by mixing and stirring all the components including component (A).

[0026] From the viewpoint of enhancing percutaneous absorbability, the hypersensitivity reducing agent of the present invention preferably has a pH of 4 to 7, more preferably 4.5 to 6.5, and even more preferably 5 to 6. In the present invention, the pH is measured at 25°C using a desktop pH meter F-72 manufactured by HORIBA.

[0027] The hypersensitivity reducing agent of the present invention can be applied to topical skin preparations, cosmetics, quasi-drugs such as pharmaceutical cosmetics, pharmaceuticals, etc., is suitable as a cosmetic, and is more preferably a skin care cosmetic.

[0028] Regarding the above-described embodiments, the present invention further discloses the following compositions. <1> A hypersensitivity reducing agent for the skin, which contains γ-amino-β-hydroxybutyric acid as an active ingredient. <2> The hypersensitivity reducing agent according to <1>, wherein the content of component (A) is preferably 0.005% by mass or more and 2% by mass or less in the total composition, more preferably 0.05% by mass or more and 1.5% by mass or less, and even more preferably 0.3% by mass or more and 1% by mass or less. <3> The hypersensitivity reducing agent according to <1> or <2>, further containing (B) a polyhydric alcohol. <4>(B) The polyhydric alcohol preferably contains one or more selected from dihydric alcohols, trihydric alcohols, and tetrahydric alcohols, more preferably contains one or more selected from trihydric alcohols and tetrahydric alcohols, and even more preferably contains one or more selected from glycerin and diglycerin. The hypersensitivity reducing agent according to <3>. <5>(B) The content of the polyhydric alcohol is preferably 1% by mass or more and 20% by mass or less in the total composition, more preferably 3% by mass or more and 15% by mass or less, and even more preferably 5% by mass or more and 12% by mass or less. The hypersensitivity reducing agent according to any one of <3> or <4>. <6>Furthermore, the hypersensitivity reducing agent according to any one of <1> to <5> contains (C) a pH adjuster. <7>The hypersensitivity reducing agent according to any one of <1> to <6> has a pH of 4 to 7. <8>Furthermore, the hypersensitivity reducing agent according to any one of <1> to <7> contains (D) an osmolyte. <9>(D) The osmolyte preferably contains one or more selected from ectoine, sodium pyrrolidonecarboxylate (PCA-Na), arginine, N-methyl-L-serine, and alanine, more preferably contains one or more selected from ectoine, sodium pyrrolidonecarboxylate (PCA-Na), and N-methyl-L-serine, and even more preferably contains sodium pyrrolidonecarboxylate (PCA-Na). The hypersensitivity reducing agent according to <8>. <10>(D) The content of the osmolyte is preferably 0.015% by mass or more and 3.5% by mass or less in the total composition, more preferably 0.02% by mass or more and 3% by mass or less, and even more preferably 0.5% by mass or more and 2% by mass or less. The hypersensitivity reducing agent according to <8> or <9>. <11>Furthermore, it contains water, and the content of water is preferably 20% by mass or more and 98.975% by mass or less in the total composition, more preferably 40% by mass or more and 90% by mass or less, and even more preferably 60% by mass or more and 85% by mass or less. The hypersensitivity reducing agent according to any one of <1> to <10>.

Examples

[0029] Example 1 Nineteen volunteer women (aged 30 to 50) with a high awareness of sensitive skin, identified through a preliminary questionnaire, were divided into two groups. A lotion (P) containing γ-amino-β-hydroxybutyric acid with the composition shown in Table 1 and a placebo lotion (Q) were each used by the respective groups for 6 weeks. Before the start of the test and after the end of the test, the degree of the "tingling and stinging sensation" that the skin feels in daily life was evaluated on the following 5-point scale, and the average values of each group were compared. The test was conducted under double-blind conditions. The results (the scores of each subject and their average values) are shown in Table 2. In Table 1, "PCA-Na 50%aq." refers to an aqueous solution of 50% by mass of sodium pyrrolidonecarboxylate. (Evaluation Criteria) 1: Not felt at all. 2: Felt very slightly and can be ignored. 3: Felt to the extent of having a weak discomfort. 4: Felt strongly and is uncomfortable. 5: Felt very strongly and intolerable.

[0030] [Table 1]

[0031] [Table 2]

[0032] From the results in Table 2, in Group P containing γ-amino-β-hydroxybutyric acid, the average score decreased from 3.3 before the start to 1.8 after 6 weeks of continuous use, confirming that it improved the skin to be less likely to feel the tingling and stinging sensation. In contrast, in Group Q, which is a placebo, no tendency for improvement was observed.

[0033] Example 2 Nineteen volunteer women (aged 30 to 50) with a high awareness of sensitive skin identified through a pre-questionnaire were divided into two groups, and they used a γ-aminobutyric acid-containing lotion (P) with the composition shown in Table 1 above and a placebo lotion (Q) in each group for 6 weeks. The degree of hypersensitivity was evaluated by measuring the electrical stimulation threshold (CPT value) at 250 Hz using a neurometer (manufactured by Neutron Co., Ltd.). The measurements were taken before the start of continuous use of the lotion, and at 4 weeks and 6 weeks after continuous use. The test was conducted under double-blind conditions. The results are shown in Figure 1. Note that a higher electrical stimulation threshold (CPT value) indicates that it is more difficult to feel the stimulation. In healthy skin, the value is about 15 (μA).

[0034] From the results in Figure 1, it was confirmed that in Group P, the CPT value at 6 weeks after the start of continuous use was significantly increased compared to that at the start of the test, indicating that it has become more difficult to feel the stimulation.

[0035] Formulation Example 1 (Lotion) (Ingredients) 1. γ-Aminobutyric acid 1.0 (mass%) 2. Citric acid appropriate amount (0.01 - 0.2) 3. Succinic acid appropriate amount (0.01 - 0.2) 4. Trisodium citrate appropriate amount (0.01 - 0.2) 5. Glycerin 5.0 6. Diglycerin 2.0 7. Sodium hyaluronate 0.1 8. Carrageenan 0.15 9. Ectoin 0.5 10. N-Methyl-L-serine 0.1 11. Sodium benzoate 0.2 12. Water residue Total 100

[0036] (Manufacturing method) While stirring water, ingredients 1 to 11 are sequentially added and dissolved, and then filtered to produce the lotion. (pH 4 - 7)

[0037] Formulation Example 2 (Beauty Liquid) (Ingredients) 1. γ-Amino-β-hydroxybutyric acid 1.5 2. Citric acid Appropriate amount (0.01 - 0.2) 3. Trisodium citrate Appropriate amount (0.01 - 0.2) 4. Glycerin 3.0 5. Diglycerin 1.0 6. 1,3-Butylene glycol 5.0 7. Carbomer Appropriate amount (0.1 - 1.0) 8. Sodium hyaluronate 0.05 9. Alanine 0.5 10. Ectoin 0.05 11. Arginine Appropriate amount (0.1 - 1.0) 12. Phenoxyethanol 0.3 13. Polyoxyethylene hydrogenated castor oil (60 E.O.) 0.2 14. Fragrance Appropriate amount 15. Water residue Total 100

[0038] (Manufacturing Method) While stirring water, ingredients 1 to 12 are sequentially added and dissolved. After separately mixing ingredients 13 and 14, they are added to the previously prepared aqueous phase to produce the beauty liquid. (pH 5 - 7) The blending amount of ingredient 7 is adjusted so that the final viscosity measured with a B-type viscometer at 30°C is 1,000 - 20,000 mPa·s.

[0039] Formulation Example 3 (Emulsion) (Ingredients) 1. γ-Amino-β-hydroxybutyric acid 0.2 (mass%) 2. Citric acid Appropriate amount (0.01 - 0.2) 3. Trisodium citrate Appropriate amount (0.01 - 0.2) 4. Glycerin 5.0 5. Carrageenan 0.2 6. N-Methyl-L-serine 0.2 7. Water The balance 8. Hydrogenated soybean phospholipid 0.5 9. Cholesterol (phytosterol) 0.5 10. Sugar squalane 8.0 11. Polyglyceryl-10 diisostearate 1.0 12. Octyldodecyl myristate 3.0 13. Isostearic acid 0.5 14. Palmitic acid 0.1 15. Dipropylene glycol 5.0 16. 1,3-Butylene glycol 3.0 17. Perfume Appropriate amount (0 - 0.5) 18. Phenoxyethanol 0.5 19. Carboxyvinyl polymer Appropriate amount (0.1 - 1.0) 20. Appropriate amount of potassium hydroxide Total 100

[0040] (Manufacturing method) Stir and dissolve Components 1 - 7 at 80°C, gradually add to Components 8 - 17 previously dissolved at 80°C, disperse with a homomixer (HM) and emulsify, then cool. Sequentially add Components 18 - 20 near 50°C, disperse again with HM, and cool to 30°C to produce an emulsion. (pH 5 - 7) The blending amount of Component 19 is adjusted so that the final viscosity measured with a B-type viscometer at 30°C is 1,500 - 15,000 mPa·s.

[0041] Formulation Example 4 (Cream) (Components) 1. γ-Amino-β-hydroxybutyric acid 2.0 (mass%) 2. Citric acid Appropriate amount (0.01 - 0.2) 3. Trisodium citrate Appropriate amount (0.01 - 0.2) 4. Phytinic acid 0.1 5. Sodium benzoate 0.2 6. Dipotassium glycyrrhizinate 0.1 7. Glycerin 5.0 8. Maltitol solution 8.0 9. Sodium Hyaluronate 0.1 10. PCA-Na 1.0 11. Water Remainder 12. Hydrogenated Soybean Phospholipid 1.0 13. Cholesterol (Phytosterol) 0.5 14. Palmitic Acid 0.2 15. Behenyl Alcohol 1.0 16. Vegetable Squalane 10.0 17. Isostearic Acid 0.5 18. Cetyl Alcohol 0.5 19. Macadamia Nut Oil 3.0 20. Jojoba Oil 3.0 21. Dipropylene Glycol 5.0 22. 1,3-Butylene Glycol 3.0 23. Perfume Appropriate amount (0 - 0.5) 24. Carboxyvinyl Polymer Appropriate amount (0.1 - 1.0) 25. Appropriate amount of potassium hydroxide Total 100

[0042] (Manufacturing Method) Stir and dissolve Components 1 - 11 at 80°C, gradually add to Components 12 - 23 previously dissolved at 80°C, disperse with a homomixer (HM) and emulsify, then cool. Sequentially add Components 24 and 25 near 50°C, disperse again with HM, cool to 30°C to produce a cream. (pH 5 - 7) The blending amount of Component 24 is adjusted so that the final viscosity measured with a B-type viscometer at 30°C is 10,000 - 100,000 mPa·s.

[0043] All of the hypersensitivity reducing agents in Formulation Examples 1 - 4 can reduce and relieve the hypersensitivity of the hypersensitive type of sensitive skin that appears to be healthy skin to that extent.

Claims

Claim 1 A skin hypersensitivity reducing agent containing (A) γ-amino-β-hydroxybutyric acid as an active ingredient. Claim 2 The hypersensitivity reducing agent according to Claim 1, wherein the content of component (A) is 0.005 to 2% by mass. Claim 3 The hypersensitivity reducing agent according to Claim 1 or 2, further containing (B) a polyhydric alcohol.

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