Agent for alleviating hypersensitivity

Abstract

The present invention relates to an agent for alleviating hypersensitivity in the skin, the agent being capable of reducing / alleviating the level of hypersensitive-type sensitive skin that is apparently healthy skin. Specifically, the present invention relates to an agent for alleviating hypersensitivity in the skin, the agent containing (A) γ-amino-β-hydroxybutyric acid as an active ingredient.

Description

Tooth sensitivity reducer

[0001] The present invention relates to a tooth sensitivity alleviating agent.

[0002] In recent years, the term "sensitive skin" has become commonly used and is frequently featured in women's magazines. When people who self-identify as having sensitive skin are asked about their symptoms, specific examples include "itching when using cosmetics," "stinging," "prone to acne and pimples," and "easily reddening even with mild irritation." Analysis of people who self-identify as having sensitive skin reveals three distinct types: I. Type with a disrupted epidermal barrier; II. Type with inflammation; and III. Type with hypersensitivity that appears healthy. It is believed that each of these three types requires appropriate care to improve sensitive skin and restore healthy skin. This is because the causes of each type are different. It has been found that type I can improve barrier function and increase tolerance to irritation by using niacinamide, which activates epidermal lipid synthesis. However, type II and III did not show any improvement because the causes of sensitive skin are different from type I. Regarding II and III, for example, previous preliminary experiments showed that treatment with plant-derived ingredients that have an NGF (nerve growth factor) inhibitory effect tends to alleviate hypersensitivity, but there is still room for further investigation (Reference 1).

[0003] On the other hand, γ-amino-β-hydroxybutyric acid is used in cosmetics and is known to have anti-aging and whitening effects on the skin (see, for example, References 2 to 4).

[0004] (Reference 1) Tomohiro Yokota, "Classification of Sensitive Skin Types by Analysis of Skin Physiological Parameters," Journal of the Japanese Society of Cosmetic Chemistry, Vol. 29, No. 1, pp. 44-19 (2005) (Reference 2) Japanese Patent Application Laid-Open No. 62-255405 (Reference 3) Japanese Patent Application Laid-Open No. 63-10708 (Reference 4) Japanese Patent Application Laid-Open No. 2003-246709

[0005] The present invention relates to a skin hypersensitivity alleviator containing (A) γ-amino-β-hydroxybutyric acid as an active ingredient. The present invention also relates to the use of (A) γ-amino-β-hydroxybutyric acid as a skin hypersensitivity alleviator. The present invention also relates to a method of using (A) γ-amino-β-hydroxybutyric acid as a skin hypersensitivity alleviator.

[0006] FIG. 1 is a graph showing the electrical stimulation threshold (CPT value) before the start of continuous use of each lotion, and after 4 and 6 weeks of continuous use in Example 2. Detailed Description of the Invention

[0007] There has been a demand for an external preparation that can reduce or alleviate the severity of sensitive skin, particularly hypersensitive skin that appears healthy.

[0008] The present inventors have found that γ-amino-β-hydroxybutyric acid has the effect of reducing or alleviating the severity of hypersensitive skin that appears to be healthy, and that γ-amino-β-hydroxybutyric acid is useful as an agent for reducing skin hypersensitivity.

[0009] One aspect of the present invention is a skin hypersensitivity alleviator containing (A) γ-amino-β-hydroxybutyric acid as an active ingredient. Another aspect of the present invention is use of (A) γ-amino-β-hydroxybutyric acid as a skin hypersensitivity alleviator. Another aspect of the present invention is a method of using (A) γ-amino-β-hydroxybutyric acid as a skin hypersensitivity alleviator.

[0010] The hypersensitivity alleviating agent of the present invention can reduce or alleviate the severity of hypersensitivity-type sensitive skin that appears to be healthy skin.

[0011] Terms used in this specification are used in the sense commonly used in the art unless otherwise specified.

[0012] In this specification, hypersensitivity of skin refers to the above-mentioned sensitive skin, that is, the skin that does not have obvious inflammation but has a sensation of burning, tingling, or tingling.The hypersensitivity reducing agent of the present invention is effective for such sensitive skin in general, but is particularly effective for the hypersensitivity type of sensitive skin (the above-mentioned type III) that appears to be healthy.Furthermore, the hypersensitivity reducing agent of the skin refers to reducing or alleviating the degree of hypersensitivity.

[0013] Component (A), γ-amino-β-hydroxybutyric acid, is a known substance and has the following chemical properties:

[0014]

[0015] From the viewpoint of reducing or mitigating the severity of hypersensitive skin that appears to be healthy, and from the viewpoint of reducing stickiness during application, the content of component (A) is preferably 0.005% by mass or more in the total composition, more preferably 0.05% by mass or more, even more preferably 0.3% by mass or more, preferably 2% by mass or less, more preferably 1.5% by mass or less, and even more preferably 1% by mass or less. Also, 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 even more preferably 0.3% by mass or more and 1% by mass or less in the total composition.

[0016] The dentin hypersensitivity alleviator of the present invention may further contain (B) a polyhydric alcohol, which can reduce or alleviate the severity of dentin hypersensitivity and reduce stickiness after application in apparently healthy skin. Note that component (B) does not include component (D), an osmolyte, which will be described later. The polyhydric alcohol is a compound having two or more hydroxyl groups in the molecule, and any polyhydric alcohol commonly used in topical skin preparations may be used. Examples of dihydric alcohols include polyethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, polypropylene glycol, 1,3-butylene glycol, and propanediol. Examples of trihydric alcohols include glycerin and trimethylolpropane. Examples of tetrahydric alcohols include diglycerin and erythritol. Examples of polyhydric alcohols having a valence of five or more include polyglycerins such as triglycerin; sugars and sugar alcohols such as glucose, maltose, maltitol, sucrose, xylitol, sorbitol, malbitol, polyoxyethylene methyl glucoside, polyoxyethylene ethyl glucoside, and polyoxyethylene propylene glucoside.

[0017] The polyhydric alcohol preferably contains one or more selected from dihydric alcohols, trihydric alcohols, tetrahydric alcohols, and sugar alcohols, more preferably one or more selected from dihydric alcohols, trihydric alcohols, and tetrahydric alcohols, even more preferably one or more selected from trihydric alcohols and tetrahydric alcohols, and even more preferably one or more selected from glycerin and diglycerin, from the viewpoint of reducing or alleviating the severity of hypersensitive sensitive skin that is apparently healthy skin, and reducing stickiness during application.

[0018] The polyhydric alcohol of component (B) can be used alone or in combination of two or more, and from the viewpoint of reducing or alleviating the degree of sensitivity of hypersensitive skin that appears to be healthy skin, reducing stickiness during application, and improving moisturizing feeling, the content is preferably 1% by mass or more in the total composition, more preferably 3% by mass or more, even more preferably 5% by mass or more, preferably 20% by mass or less, more preferably 15% by mass or less, and even more preferably 12% by mass or less.Furthermore, the content of component (B) is preferably 1% by mass or more and 20% by mass or less, 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 in the total composition.

[0019] The dentin hypersensitivity alleviator of the present invention can further contain (C) a pH adjuster, which can reduce or alleviate the severity of dentin hypersensitivity-type sensitive skin that appears healthy, and improve the stability of the formulation. Note that component (C) does not include component (D), an osmolyte, which will be described later. The pH adjuster may be any pH adjuster commonly used in topical skin preparations, with inorganic acids and their salts, and organic acids having 6 or fewer carbon atoms and their salts being preferred, and organic acids having 6 or fewer carbon atoms and their salts being more preferred. The inorganic acid 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. Furthermore, the organic acid having 6 or fewer carbon atoms and its salts is preferably a water-soluble organic acid and its salt, such as a fatty acid, hydroxy acid, or dicarboxylic acid having 1 to 6 carbon atoms, and its salts. 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 salts thereof, more preferable to contain one or more selected from malic acid, lactic acid, citric acid, succinic acid, and salts thereof, and even more preferable to contain one or more selected from citric acid and salts thereof.

[0020] The pH adjuster of component (C) can be used alone or in combination of two or more, and from the viewpoint of reducing or alleviating the degree of the hypersensitive type sensitive skin that is apparently healthy skin, from the viewpoint of improving the stability of the preparation, and from the viewpoint of obtaining pH buffering ability, the content is preferably 0.01% by mass or more in the whole composition, 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 whole composition, more preferably 0.03% by mass or more and 0.5% by mass or less, even more preferably 0.05% by mass or more and 0.3% by mass or less.

[0021] The dentin hypersensitivity alleviator of the present invention can further contain (D) an osmolyte, which can reduce or alleviate the severity of dentin hypersensitivity and reduce stickiness after application in apparently healthy skin. Note that component (D) does not include component (B) a polyhydric alcohol or component (C) a pH adjuster. Examples of osmolytes include ectoine, sodium pyrrolidonecarboxylate (PCA-Na), arginine, arginine hydrochloride, carnitine chloride, taurine, glutamic acid, glutamate, serine, N-methyl-L-serine, trimethylglycine, and alanine. From the viewpoint of reducing or alleviating the severity of hypersensitive skin that is apparently healthy, and reducing stickiness during application, the osmolyte preferably contains one or more selected from ectoine, sodium pyrrolidone carboxylate (PCA-Na), arginine, N-methyl-L-serine, and alanine, more preferably one or more selected from ectoine, sodium pyrrolidone carboxylate (PCA-Na), and N-methyl-L-serine, and even more preferably sodium pyrrolidone carboxylate (PCA-Na).

[0022] The osmolyte of component (D) can be used alone or in combination of two or more, and from the viewpoint of reducing and mitigating the degree of the hypersensitive type sensitive skin that is apparently healthy skin, and from the viewpoint of reducing the stickiness during application, its 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.In addition, 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, even more preferably 0.5% by mass or more and 2% by mass or less.

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

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

[0025] The dentin hypersensitivity alleviating agent of the present invention can be produced by a conventional method, for example, by mixing and stirring all the components including component (A).

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

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

[0028] In relation to the above-described embodiment, the present invention further discloses the following composition. <1> A skin hypersensitivity reducer containing (A) γ-amino-β-hydroxybutyric acid as an active ingredient. <2> The hypersensitivity reducer according to <1>, wherein 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 even more preferably 0.3% by mass or more and 1% by mass or less, based on the total composition. <3> The hypersensitivity reducer according to <1> or <2>, further comprising (B) a polyhydric alcohol. <4> The hypersensitivity reducer according to <3>, wherein (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. <5> The dentin hypersensitivity reducer according to any one of <3> or <4>, wherein the content of (B) polyhydric alcohol is preferably 1% by mass or more and 20% by mass or less, 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, based on the total composition. <6> The dentin hypersensitivity reducer according to any one of <1> to <5>, further comprising (C) a pH adjuster. <7> The dentin hypersensitivity reducer according to any one of <1> to <6>, having a pH of 4 to 7. <8> The dentin hypersensitivity reducer according to any one of <1> to <7>, further comprising (D) an osmolyte. <9> The dentin hypersensitivity reducer according to <8>, wherein the (D) osmolyte preferably comprises one or more selected from ectoine, sodium pyrrolidone carboxylate (PCA-Na), arginine, N-methyl-L-serine, and alanine, more preferably one or more selected from ectoine, sodium pyrrolidone carboxylate (PCA-Na), and N-methyl-L-serine, and even more preferably sodium pyrrolidone carboxylate (PCA-Na). <10> The dentin hypersensitivity reducer according to <8> or <9>, wherein the content of the (D) osmolyte is preferably 0.015% by mass or more and 3.5% by mass or less, 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, of the total composition.<11> The dentin hypersensitivity reducer according to any one of <1> to <10>, further comprising water, wherein the water content of the total composition is preferably 20% by mass or more and 98.975% by mass or less, 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. <12> Use of (A) γ-amino-β-hydroxybutyric acid as a skin dentin hypersensitivity reducer. <13> A method of using (A) γ-amino-β-hydroxybutyric acid as a skin dentin hypersensitivity reducer.

[0029] Example 1 Nineteen female volunteers (aged 30 to 50) who were highly aware of sensitive skin, as determined by a preliminary questionnaire, were divided into two groups, and each group used a γ-amino-β-hydroxybutyric acid-containing lotion (P) with the composition shown in Table 1 and a placebo lotion (Q) for six weeks. Before and after the test, the subjects rated the level of "tingling / stinging" they felt on their skin in their daily lives using the following five-point scale, and the average scores for each group were compared. The test was conducted under double-blind conditions. The results (each subject's score and its average) are shown in Table 2. In Table 1, "PCA-Na 50% aq." refers to a 50% by mass aqueous solution of sodium pyrrolidonecarboxylate. (Evaluation Criteria) 1: No sensation at all. 2: Very slight sensation, but negligible. 3: Slight discomfort. 4: Strong and uncomfortable sensation. 5: Very strong sensation, unbearable.

[0030]

[0031]

[0032] From the results in Table 2, it was confirmed that in Group P containing γ-amino-β-hydroxybutyric acid, the average score before the start was 3.3, but after 6 weeks of continuous use the average score decreased to 1.8, and the skin became less sensitive to tingling and burning sensations. In contrast, no tendency for improvement was observed in Group Q, which was the placebo.

[0033] Example 2 Nineteen female volunteers (aged 30-50) with a high awareness of sensitive skin, as determined by a preliminary questionnaire, were divided into two groups, and each group used a γ-amino-β-hydroxybutyric acid-containing lotion (P) with the composition shown in Table 1 above and a placebo lotion (Q) for six weeks. The level of hypersensitivity was evaluated by measuring the electrical stimulation threshold (CPT value) at 250 Hz using a Neurometer (manufactured by Neutron Corporation). Measurements were taken before the start of continuous use of the lotion, and after four and six weeks of continuous use. The test was conducted under double-blind conditions. The results are shown in Figure 1. Note that a higher CPT value indicates less sensitivity to irritation. For healthy skin, the CPT value is approximately 15 (μA).

[0034] From the results shown in Figure 1, it was confirmed that the CPT value of Group P increased significantly after 6 weeks of continuous use compared to the value at the start of the test, and that irritation became less noticeable.

[0035] Formulation Example 1 (Lotion) (Ingredients) 1. γ-amino-β-hydroxybutyric acid 1.0 (mass %) 2. Citric acid appropriate amount (0.01 to 0.2) 3. Succinic acid appropriate amount (0.01 to 0.2) 4. Trisodium citrate appropriate amount (0.01 to 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 0.21 2. Water Remaining Total 100

[0036] (Production Method) Components 1 to 11 are added to water in order while stirring, dissolved, and filtered to produce a lotion (pH 4 to 7).

[0037] Formulation Example 2 (Serum) (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. Carboxyvinyl polymer Appropriate amount (0.1-1.0) 8. Sodium hyaluronate 0.05 9. Alanine 0.5 10. Ectoine 0.05 11. Arginine Appropriate amount (0.1-1.0) 12. Phenoxyethanol 0.3 13. Polyoxyethylene hydrogenated castor oil (60E.O.) 0.2 14. Fragrance Appropriate amount 15. Water Remaining Total 100

[0038] (Production Method) Components 1 to 12 are added sequentially to water while stirring and dissolved, and then components 13 and 14 are added separately to the pre-mixed aqueous phase to produce a cosmetic serum (pH 5 to 7). The amount of component 7 is adjusted so that the final viscosity is 1,000 to 20,000 mPa s as measured with a Brookfield viscometer at 30°C.

[0039] Formulation Example 3 (Emulsion) (Ingredients) 1. γ-amino-β-hydroxybutyric acid 0.2 (mass%) 2. Citric acid Appropriate amount (0.01 to 0.2) 3. Trisodium citrate Appropriate amount (0.01 to 0.2) 4. Glycerin 5.0 5. Carrageenan 0.2 6. N-methyl-L-serine 0.2 7. Water (remaining) 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. Fragrance appropriate amount (0-0.5) 18. Phenoxyethanol 0.5 19. Carboxyvinyl polymer appropriate amount (0.1-1.0) 20. Potassium hydroxide appropriate amount Total 100

[0040] (Production Method) Components 1 to 7 are dissolved with stirring at 80°C, gradually added to components 8 to 17 previously dissolved at 80°C, dispersed and emulsified using a homomixer (HM), and then cooled. Components 18 to 20 are added sequentially at around 50°C, dispersed again using a HM, and cooled to 30°C to produce an emulsion. (pH 5 to 7) The amount of component 19 is adjusted so that the final viscosity, measured with a Brookfield viscometer at 30°C, is 1,500 to 15,000 mPa s.

[0041] Formulation Example 4 (Cream) (Ingredients) 1. γ-amino-β-hydroxybutyric acid 2.0 (mass%) 2. Citric acid Appropriate amount (0.01 to 0.2) 3. Trisodium citrate Appropriate amount (0.01 to 0.2) 4. Phytic 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 (remaining) 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. 18. Isostearic acid 0.5 19. Cetyl alcohol 0.5 20. Macadamia nut oil 3.0 21. Dipropylene glycol 5.0 22. 1,3-butylene glycol 3.0 23. Fragrance (0-0.5) 24. Carboxyvinyl polymer (0.1-1.0) 25. Potassium hydroxide (0.1-1.0) Total 100

[0042] (Production Method) Components 1 to 11 are dissolved with stirring at 80°C, gradually added to components 12 to 23 previously dissolved at 80°C, dispersed and emulsified using a homomixer (HM), and then cooled. Components 24 and 25 are added sequentially at around 50°C, dispersed again using a HM, and cooled to 30°C to produce a cream. (pH 5 to 7) The amount of component 24 is adjusted so that the final viscosity, measured with a Brookfield viscometer at 30°C, is 10,000 to 100,000 mPa s.

[0043] The hypersensitivity alleviating agents of Formulation Examples 1 to 4 can alleviate or mitigate the severity of hypersensitive skin that appears healthy.

Claims

1. A skin hypersensitivity reducing agent containing (A) γ-amino-β-hydroxybutyric acid as an active ingredient.

2. The hypersensitivity reducing agent according to claim 1, wherein the content of the component (A) is 0.005 to 2% by mass.

3. The hypersensitivity reducing agent according to claim 1 or 2, further containing (B) a polyhydric alcohol.

4. Use of (A) γ-amino-β-hydroxybutyric acid as a skin hypersensitivity reducing agent.

5. A method of using (A) γ-amino-β-hydroxybutyric acid as a skin hypersensitivity reducing agent.

Images