JP2022051529A - External preparation for skin - Google Patents

Abstract

To provide an external preparation for skin that uses the action of nicotinamide to inhibit a discomfort sulfur odor caused by the combination of tranexamic acid and a sulfur-containing compound.SOLUTION: An external preparation for skin contains following components (A), (B) and (C): (A) tranexamic acid, (B) a sulfur-containing compound and (C) nicotinamide. The sulfur content (b1) in the component (B) is 0.0001 mass% or more; the mass ratio of the content of the component (A) to the (b1), (A)/(b1), is 10-10000; the mass ratio of the content of the component (C) to the (b1), (C)/(b1), is 10-10000.SELECTED DRAWING: None

Description

The present invention relates to an external skin preparation.

Tranexamic acid is used as an active ingredient in pharmaceutical products because it has hemostatic and anti-inflammatory effects, and is also widely used in cosmetics and external skin preparations because it has rough skin improving and whitening effects (for example). Patent Documents 1 and 2). Further, the sulfur-containing compound is a component widely used in cosmetics and external skin preparations for the purposes of moisturizing, moisturizing, skin conditioning, whitening and the like (for example, Patent Documents 3, 4, 5 and 6).

Japanese Unexamined Patent Publication No. 1-93519 Japanese Unexamined Patent Publication No. 2008-100933 Japanese Unexamined Patent Publication No. 62-175415 Japanese Unexamined Patent Publication No. 63-8315 Japanese Unexamined Patent Publication No. 2-145507 Japanese Unexamined Patent Publication No. 5-222030

On the other hand, the sulfur-containing compounds disclosed in Patent Documents 3, 4, 5 and 6 have an unpleasant sulfur odor and may cause a change in odor from the initial stage to the aging period. Therefore, depending on the blending amount, problems such as difficulty in using it on the face may occur, and the range and site of use may be limited. In addition, we tried to use a sulfur-containing compound and tranexamic acid in combination for the purpose of further enhancing the useful effect on the skin, but there is a problem that the sulfur odor worsens, so both tranexamic acid and a flow-containing compound are mixed. It was difficult to develop a skin external preparation.

As a result of diligent studies in the above circumstances, the present inventors have found that the combined use of nicotinamide with tranexamic acid and a sulfur-containing compound suppresses the deterioration of the sulfur odor of the sulfur-containing compound due to tranexamic acid. , The present invention has been completed. Hereinafter, it will be described in detail.
That is, in the present invention, the components (A) to (C):
(A) Tranexamic acid (B) sulfur-containing compound (C) nicotinic acid amide is contained, and the sulfur content mass% (b1) in the component (B) in the external skin preparation is 0.0001% by mass or more. Skin in which the content mass ratio (A) / (b1) of the components (A) and (b1) is 10 to 10000, and the content mass ratio (C) / (b1) of the components (C) and (b1) is 10 to 10000. It provides an external preparation.

Further, the content mass ratios of the components (A), (C) and (b1) are 15 to 8000 for (A) / (b1), and the content mass ratios (C) / (b1) of the components (C) and (b1). ) Provides a skin external preparation having a value of 20 to 9000.

Further, the present invention provides an external skin preparation having a mass ratio (C) / (A) of 0.01 or more of the components (A) and (C).

Further, the sulfur-containing compound of the component (B) provides one or more kinds of external skin preparations selected from amino acids, surfactants, and extracted components of seaweeds.

Further, the sulfur-containing compound of the component (B) provides one or more kinds of external skin preparations selected from cysteine, glutathione and carrageenan.

Further, the present invention provides a deodorant inhibitor that suppresses the deterioration of the sulfur odor generated by containing tranexamic acid in a skin external preparation containing a sulfur-containing compound by containing nicotinamide.

The present invention relates to an external skin preparation having an excellent effect of suppressing an unpleasant sulfur odor exacerbated by the combined use of tranexamic acid and a sulfur-containing compound.

Hereinafter, the present invention will be described in detail. In addition, in this specification, "-" shall mean the range including the numerical values before and after it. Hereinafter, "mass%" is simply abbreviated as "%".
The component (A) tranexamic acid used in the present invention is also known as trans-4-aminomethylcyclohexane-1-carboxylic acid, and is a compound having both an amino group and a carboxyl group in the molecule. The tranexamic acid used in the present invention may be contained in its original form, or may be in the form of a salt, an ester of a carboxyl group of tranexamic acid and a fatty acid, or a derivative such as an amino group of tranexamic acid and an amide of a fatty acid. Specific examples thereof include ester derivatives such as tranexamic acid cetyl ester; amide derivatives such as tranexamic acid methylamide, and tranexamic acid cetyl hydrochloride.

The content of the component (A) of the present invention in the external skin preparation may be limited to the extent that the desired effect / effect of the component (A) can be exhibited, and is not particularly limited, but is usually 0.1. It can be contained in an amount of about 10%, preferably 0.5 to 8%, more preferably 1.0 to 5%.

The sulfur-containing compound of the component (B) used in the present invention is not particularly limited, but is contained for the purpose of keratin dissolving effect, bactericidal effect, antioxidant effect, whitening effect, hair nourishing effect, indulgence prevention effect and the like. A plant containing, for example, sulfur, cysteine, cystine, acetylcysteine, cysteine hydrochloride, methionine, glutathione, α-lipoic acid, and a sulfur-containing compound, as long as it is used as a raw material for a normal skin external preparation. , Seaweed, seaweed extract and the like. These sulfur-containing compounds may be used alone or in combination of two or more, if necessary.

The content of the component (B) of the present invention in the external skin preparation may be limited to the extent that the desired effect / effect of the component (B) can be exhibited, and the content is not particularly limited, but the component (B) When the sulfur content in mass% is represented by (b1), it is usually 0.0001 to 0.3%, preferably 0.0002 to 0.25%, and more preferably 0.001 to 0.2%. be able to. When an extract is used, the concentration of the extract is not limited as long as the amount of the solute is within the above range.

The above-mentioned (b1) is expressed in detail by the following formula.
<(B1) = (Mass content% of component (B) in the external skin preparation) × (Molecular weight of sulfur: 32.1) / (Molecular weight of component (B))>

Further, the content mass ratio of the component (A) and the component (b1) is not particularly limited, but from the viewpoint of the balance of deterioration of the odor of the component (B) due to the component (A), the upper limit of (A) / (b1). It is 10000, preferably 8000 or less, more preferably 4000 or less, and the lower limit of (A) / (b1) is 10, preferably 15 or more, and 20 or more. More preferred.

The nicotinamide of the component (C) in the present invention is an amide compound of nicotinic acid (vitamin B3, also called niacin), and is also called nicotinamide or niacinamide. Nicotinamide is a water-soluble vitamin, which is a known substance that is one of the B vitamins, and can be extracted from natural products (rice bran, etc.) or synthesized by a known method. Specifically, those listed in the 15th revised Japanese Pharmacopoeia 2008 can be used.

The content of the component (C) in the present invention is not particularly limited, and is preferably 0.1 to 10% from the viewpoint of suppressing deterioration of the sulfur odor generated by containing (B). It is more preferably 0.5 to 8.5%, and particularly preferably 1 to 7%.

Further, the content mass ratio of (b1) and the component (C) is (C) / (b1) = 10 to 10000 from the viewpoint of suppressing the sulfur odor derived from the component (C), and is 20 to 20. It is preferably 9000, more preferably 40 to 8000.

The content mass ratio of the component (A) and the component (C) is not particularly limited, but (C) / (A) = 0.01 or more from the viewpoint of the sulfur odor suppressing effect of the component (C) with respect to the component (A). It is preferably 0.05 or more, more preferably 0.1 or more, and particularly preferably 0.1 or more.

The skin external preparation of the present invention includes, as necessary, components used in the preparation of skin external preparations, fragrances, deodorants, etc., in addition to the above-mentioned components, as long as the effects of the present invention are not impaired. Water (purified water, hot spring water, deep water, etc.), oils, surfactants, metal keratins, gelling agents, powders, water-soluble polymers, film-forming agents, resins, UV protection agents, inclusion compounds, antibacterial agents , Fragrances, deodorants, salts, pH adjusters, refreshing agents, animal / microorganism-derived extracts, plant extracts, blood circulation promoters, astringents, anti-fat leak agents, whitening agents, anti-inflammatory agents, active oxygen scavengers , Cell activator, moisturizer, chelating agent, keratolytic agent, enzyme, hormones, vitamins other than the component (C) and the like can be added.

The method for producing the external skin preparation of the present invention is not particularly limited, and is prepared by a conventional method. For example, the above-mentioned components (A) to (C) may be prepared by adding the above-mentioned optional components as necessary and mixing them.

The external skin preparation of the present invention can be carried out in various forms such as liquid, gel, cream, solid, and mousse, and is contained in a container that can be sprayed into a mist and sprayed into a mist. May be used. The dosage form of the product of the present invention is not particularly limited, such as a solubilized type, an oil-in-water type, a water-in-oil type, an oil-based type, a water-in-oil-in-water type, an oil-in-oil-in-oil type, and a multilayer type.

The use of the external skin preparation of the present invention is not particularly limited, and can be used as a composition for various purposes such as cosmetics, external skin preparations, fragrances, and deodorants. The composition of the present invention is preferably used as a cosmetic or a skin external preparation from the viewpoint of being excellent in anti-aging effect and the like.

Examples of the external preparation for skin of the present invention are not particularly limited, and are, for example, skin care cosmetics such as milky lotion, cream, lotion, beauty liquid, and pack, foundation, cheek, lipstick, eye color, mascara, eyeliner, and manicure. Makeup cosmetics such as hair tonics, hair tonics, shampoos, rinses, hair waxes and other hair cosmetics, washing pigments and other cleaning agents, external gels, creams, ointments, liquids, liniments, paps, etc. It may be in any form such as an aerosol agent.

(Products 1-1 to 10-1, Comparative Examples 11-1 to 15-1, Reference Examples 1-2 to 15-2, 1-3 to 15-3 ,: Toner)
Toners having the compositions shown in Tables 1 to 5 below were prepared by the following production methods, and the odor suppressing effect was evaluated and judged by the methods shown below, and the results are also shown in Tables 1 to 5. The above reference example is an evaluation of the sulfur odor of the component (B) alone that does not contain the components (A) and (C), and the sulfur odor of the component (B) due to the component (C) that does not contain the component (A). This is an example of confirming the deterioration of.

(Production method)
A: The components (6) and (7) are uniformly dissolved.
B: The components (1) and (2) are uniformly dissolved in A.
Ingredients (3) to (5) are added to C: B and dissolved.

(Evaluation methods)
The above lotion was subjected to sensory evaluation of the odor immediately after production using five professional evaluators, and the effectiveness of the odor suppressing effect was evaluated according to the following (a) effectiveness rank, and the following (b) judgment criteria. Judgment by.

(B) Effectiveness rank 0 points: No sulfur odor is generated 1 point: Sulfur odor is hardly generated 2 points: Sulfur odor is slightly generated 3 points: Sulfur odor is generated 4 points: Sulfur odor is generated Is significant

(B) The average value of the effectiveness ranks of (Reference Example X-3) and (Product X-1 of the present invention) judged by the judgment criteria (a) was calculated, and from (Reference Example X-3) to (Product of the present invention). The rate of change minus the value of X-1) was determined according to the following criteria. In addition, X means the number at the beginning of the prescription number of each product of the present invention, the reference product, and the comparative example.
○: Change rate is 0.5 points or more △: Change rate is 0 points or more and less than 0.5 points ×: Change rate is less than 0 points (when the sulfur odor worsens due to the addition of component A)

As is clear from the results in Tables 1 to 5, in the lotion of the products 1-1 to 10-1 of the present invention, the odor of the component (B) was caused by the component (A). When compared with 10-3, all of them were excellent in the effect of suppressing odor by containing the component (C). On the other hand, in Comparative Example 11-1, when Reference Examples 11-2 and 11-3 were compared, the component (A) was small and no odor was generated. Regarding Comparative Examples 12-1 and 13-1, when compared with Reference Examples 12-2, 12-3, and 13-2, 13-3, respectively, the amount of the component (C) was compared with the amount of the component (A). Due to the small amount, the suppression of odor by the component (A) was not sufficient. In Comparative Example 14-1, since the amount of the component (B) was very small, the sulfur odor itself was not generated, and the suppression of the odor change by the component (C) could not be evaluated. In Comparative Example 15-1, the amount of the component (B) was excessive and the sulfur odor could not be suppressed.

[Prescription example 1: Toner]
(Manufacturing method)
A. The following components (8) to (13) are mixed and dissolved.
B. The following components (1) to (7) and (14) are mixed and dissolved.
C. A was added to the B and mixed to obtain a lotion.
(Ingredient) (%)
1. 1. Glycerin 5.0
2.1,3-butylene glycol 5.0
3. 3. Lactic acid 0.05
4. Sodium lactate 0.1
5. Tranexamic acid 5.0
6. Nicotinamide 1.0
7. Cysteine 0.01
8. Polyoxyethylene (60 mol) hardened castor oil 1.2
9. Polyoxyethylene (40 mol) hardened castor oil 0.5
10. Ethanol 8.0
11. Synthetic Vitamin E 0.001
12. Methyl paraoxybenzoate 0.1
13. Fragrance 0.1
14. Remaining amount of purified water

(B1): 0.01 × 32.1 / 121.2 = 0.0027
(A) / (b1): 5.0 / 0.0027 = 1886.30
(C) / (b1): 1.0 / 0.0027 = 377.26
The lotion of Formulation Example 1 had no odor and had good stability over time.

[Prescription example 2: Essence]
(Manufacturing method)
A. The following components (1) to (12) are mixed and dissolved.
B. The following components (13) to (18) are mixed and dissolved.
C. B was added to A and mixed to obtain a beauty essence.
(Ingredient) (%)
1. 1. Dipropylene glycol 5.0
2.1,3-butylene glycol 8.0
3. 3. Acrylic acid / alkyl methacrylate (C10-30)
Cross polymer 0.2
4. Xanthan gum 0.2
5. Remaining amount of purified water 6. Sodium hydroxide 2% aqueous solution 2.0
7. Cysteine 0.05
8. Sodium hyaluronate 0.01
9. Hydrolyzed elastin 0.01
10. Hydrolyzed collagen 0.1
11. Tranexamic acid 1.0
12. Nicotinamide 5.0
13. Polyoxyethylene (60 mol) hardened castor oil 0.5
14. Isostearic acid 0.2
15. Naturally-derived Vitamin E 0.01
16. Methyl paraoxybenzoate 0.1
17. Ethanol 2.0
18. Fragrance 0.02

(B1): 0.05 × 32.1 / 121.1 = 0.013
(A) / (b1): 1.0 / 0.013 = 75.45
(C) / (b1): 5.0 / 0.013 = 377.26
The beauty essence of Formulation Example 2 had no odor and had good stability over time.

[Prescription example 3: Oil-in-water emulsion]
(Manufacturing method)
A. The components (1) to (6) are uniformly dissolved and mixed at 70 ° C.
B. The components (7) to (15) are uniformly dissolved and mixed at 80 ° C.
C. B is added to A and emulsified at 70 ° C.
D. After the components (16) to (20) were added to and mixed with C, the mixture was cooled to 40 ° C. to obtain an oil-in-water emulsion.
(Ingredient) (%)
1.1,3-butylene glycol 5.0
2. 2. Dipropylene glycol 5.0
3. 3. Remaining amount of purified water 4. Tranexamic acid 1.0
5. Nicotinamide 5.0
6. Sodium hydroxide 2% aqueous solution 0.2
7. N-myristoyl-L-glutamic acid 0.2
8. Polyoxyethylene (10 mol) hardened castor oil 0.2
9. Macadamia nut oil fatty acid phytosteryl 1.0
10. Tri (caprylic acid / caprylic acid) glyceryl 0.2
11. Natural Vitamin E 1.0
12. N-stearoylphytosphingosine 0.1
13. Tocopherol acetate 0.01
14. Stearyl alcohol 0.5
15.1,2-Pentanediol 0.1
16. Carboxyvinyl polymer 0.15
17. (Na acrylate / Na acryloyldimethyltaurine)
Copolymer 2.0
18. Glutathione 0.01
19. Ethanol 5.0
20. Fragrance 0.1

(B1): 0.01 × 32.1 / 307.3 = 0.0010
(A) / (b1): 1.0 / 0.0010 = 957.32
(C) / (b1): 5.0 / 0.0010 = 4786.60
The oil-in-water emulsion of Formulation Example 3 had no odor change and had good stability over time.

[Prescription example 4: Oil-in-water cream]
(Manufacturing method)
A: The components (1) to (9) are heated and dissolved at 70 ° C.
B: After heating the components (10) to (17) at 70 ° C., the above A is added and emulsified.
C: The B was cooled to room temperature, and (18) to (20) were added and mixed to obtain an oil-in-water cream.

(Ingredient) (%)
1. 1. Synthetic Vitamin E 3.0
2. 2. Docosahexaenoic acid (DHA) 1.0
3. 3. Polyoxyethylene monooleate (20) Sorbitan 2.0
4. Polyoxyethylene alkyl ether phosphoric acid 0.3
5. Propylene Glycol Dicaprate 1.7
6. Squalene 3.5
7. Setostearyl alcohol 3.0
8. Vaseline 2.0
9. Jojoba oil 1.0
10. Tranexamic acid 2.0
11.1,3-butylene glycol 2.0
12. Glycerin 10.0
13. Carboxyvinyl polymer 0.3
14. Carrageenan 0.1
15. Appropriate amount of sodium hydroxide 16. Remaining amount of purified water 17. Nicotinamide 1.0
18. Methyl paraoxybenzoate 0.3
19. Ethanol 7.0
20. Fragrance 0.2

(B1): 0.1 × 32.1 / 200.6 = 0.016
(A) / (b1): 2.0 / 0.016 = 124.99
(C) / (b1): 1.0 / 0.016 = 62.50
The oil-in-water cream of Formulation Example 4 had little odor and good stability over time.

[Prescription Example 5: Oil-in-water liquid foundation]
(Manufacturing method)
A: The components (16) to (23) are dispersed by a three-roller.
B: Ingredients (1) to (8) are heated at 90 ° C. and uniformly mixed.
C: (9) heated to about 90 ° C. was added to the B, emulsified, cooled, and (10) to (15) were added.
D: A is mixed with C. E: The D is filled in a container to obtain an oil-in-water liquid foundation.
(Ingredient) (%)
1. 1. Polyoxyethylene (60) Hardened Castor Oil 0.5
2. 2. Polyoxyethylene (20) sorbitol with tetraoleate 1.0
3. 3. (Dimethicone / Vinyl Dimethicone)
Cross-polymer mixture (solid content 5%) 10.0
4. Methyltrimethicone 5.0
5. Octyl methoxycinnamate 3.0
6. Bisethylhexyloxyphenol methoxyphenyl triazine 5.0
7. Acrylic-Silicone Graft Copolymer Solution 5.0
8. Natural Vitamin E 0.00001
9. Remaining amount of purified water 10. Tranexamic acid 3.0
11. (Sodium Acrylate / Acryloyl Dimethyl Taurine Sodium) Copolymer 1.0
12. Phenoxyethanol 0.3
13.1,3-butylene glycol 10.0
14. Red algae extract 0.05
15. Nicotinamide 2.0
16. Alkyl Acrylic Polymer Emulsion 3.0
17. Triethanolamine 3.5
18. Black iron oxide 0.2
19. Bengala 1.3
20. Titanium oxide 8.0
21. Yellow iron oxide 0.5
22. Sericite 5.0
23. Red No. 202 0.2

(B1) 0.05 × 32.1 / 946.7 = 0.0017
(A) / (b1): 3.0 / 0.0017 = 1769.53
(C) / (b1): 2.0 / 0.0017 = 1179.69
The oil-in-water liquid foundation of Formulation Example 5 had no odor and had good stability over time.

[Prescription example 6: Impregnation mask]
(Manufacturing method)
A: The components (1) to (5) are heated and dissolved at 70 ° C.
B: Ingredients (6) to (11) are heated and dissolved at 70 ° C., then added to A and emulsified.
C: The B was cooled to room temperature, (12) to (15) were added and mixed to obtain an oil-in-water emulsion.
D: The C was impregnated into a non-woven fabric (material: cellulose) to obtain an impregnated mask.
(Ingredient) (%)
1. 1. Dipropylene glycol 10.0
2. 2. Polyoxyethylene (40) Hardened Castor Oil 0.5
3. 3. Methyl paraoxybenzoate 0.1
4. Squalene 0.5
5. Natural Vitamin E 0.01
6. Nicotinamide 1.0
7. Glycerin 10.0
8. Remaining amount of purified water 9. Hot spring water 1.0
10. Appropriate amount of sodium hydroxide 11. Tranexamic acid 1.0
12. Carboxyvinyl polymer 0.1
13. Xanthan gum 0.05
14. Cysteine 0.005
15. Fragrance 0.2

(B1): 0.005 × 32.1 / 121.2 = 0.0013
(A) / (b1): 1.0 / 0.0013 = 755.14
(C) / (b1): 1.0 / 0.0013 = 755.14
The impregnated mask of Formulation Example 6 had no odor and had good stability over time.

[Prescription example 7: Oil-in-water hand cream]
(Manufacturing method)
A: The components (1) to (12) and (26) are mixed and dissolved at 70 ° C.
B: The components (13) to (25) are mixed and dissolved at 70 ° C.
C: A is added to B while stirring to emulsify.
D: The C was cooled to room temperature to obtain an oil-in-water hand cream.
(Ingredient) (%)
1. 1. Polyethylene glycol monostearate 2.0
2. 2. Glycerin monostearate 3.0
3. 3. Setostearyl alcohol 2.0
4. Behenyl alcohol 3.0
5. Liquid paraffin 4.0
6. Vaseline 10.0
7. Di (octyldodecyl / phytosteryl / behenyl) lauroyl glutamate 2.0
8. Oleyl oleate 1.0
9. Coenzyme Q10 0.2
10. Linoleic acid 0.04
11. Natural Vitamin E 0.01
12. Retinyl palmitate 0.3
13. Methyl paraoxybenzoate 0.2
14. Concentrated glycerin 5.0
15.1,3-butylene glycol 10.0
16. Phosphoric acid 1 sodium hydrogen hydrogen 0.1
17. Sodium dihydrogen phosphate 0.1
18. Disodium edetate 0.1
19. Appropriate amount of sodium hydroxide 20. Remaining amount of purified water 21. Chondroitin sulfate Na 0.05
22. Royal jelly extract 0.1
23. Magnesium Ascorbic Acid Phosphate 0.5
24. Tranexamic acid 3.0
25. Nicotinamide 3.0
26. Fragrance 0.2

(B1): 0.05 × 32.1 × 3 / 1526.03 = 0.0032
(A) / (b1): 3 / 0.0032 = 950.80
(C) / (b1): 3 / 0.0032 = 950.80
The hand cream of Formulation Example 7 had no odor and had good stability over time.

Claims (6)

The following components (A), component (b) and component (C);
(A) Tranexamic acid (B) Sulfur-containing compound (C) Nicotinic acid amide is contained, and the content mass% of the component (B) is multiplied by the sulfur content obtained by converting the sulfur content in the component (B) by the molecular weight. In this case, the sulfur content mass% (b1) in the external preparation for skin is 0.0001 mass% or more, the content mass ratio (A) / (b1) of the components (A) and (b1) is 10 to 10,000, and the component (b1). A skin external preparation having a mass ratio (C) / (b1) of C) and (b1) of 10 to 10000. The content mass ratio of the components (A), (C), and (b1) is 15 to 8000 for (A) / (b1), and the content mass ratio (C) / (b1) of the component (C) and the component (b1). The external skin preparation according to claim 1, wherein the amount is 20 to 9000. The external skin preparation according to claim 1 or 2, wherein the content mass ratio (C) / (A) of the components (A) and (C) is 0.01 or more. The skin external preparation according to any one of claims 1 to 3, wherein the sulfur-containing compound of the component (B) is one or more selected from amino acids, surfactants, and extracted components of seaweed. The skin external preparation according to any one of claims 1 to 4, wherein the sulfur-containing compound of the component (B) is one or more selected from cysteine, glutathione, and carrageenan. A deodorant inhibitor that suppresses the deterioration of the sulfur odor generated by containing tranexamic acid in a skin external preparation containing a sulfur-containing compound by containing nicotinamide.