JPS61225108A - Agent for skin application - Google Patents

Abstract

PURPOSE:To provide the titled agent for skin application, containing at least one of the products obtained by the reaction of retinoic acid and sulfur, retinol and sulfur, or retinoic acid, retinol and sulfur, and effective to the prevention, remedy or treatment of acne and the prevention of dandruff. CONSTITUTION:The objective agent for skin application contains one or more components selected from (A) a reaction product of retinoic acid [3,7- dimethyl-9-(2, 6, 6-trimethyl-1-cyclohexen-1-yl)-2, 4, 6, 8-nonatetraenoic acid of for-mula I] with sulfur, (B) a reaction product of retinol of formula II with sulfur and (C) a reaction product of retinoic acid, retinol and sulfur. The irrita tion of sulfur compound to the skin is remarkably mitigated and the excellent cuticle-peeling activity of retinoic acid or retinol can be effectively utilized. Even if the agent contains an oily component, it is resistant to the deterioration caused by the oxidative degradation of the oil.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a skin application containing a reaction product of retinoic acid or retinol with sulfur as an active ingredient.

This skin application is particularly effective in the prevention, treatment, and treatment of acne (so-called acne), and can also be used on the scalp to effectively prevent dandruff.

[Prior Art] Sulfur has heretofore been used in combination with skin ointments or skin cosmetics, but in this case the sulfur has been in the form of powder or dispersion.

[Problem to be solved by the invention 1] Therefore, when conventional products are applied to the skin, most of the sulfur merely serves to cover the skin surface, and only a small portion of the sulfur has medicinal or cosmetic effects. was not involved. Therefore, it is not possible to expect a satisfactory effect from conventional products, and in order to obtain a strong effect, it is necessary to increase the amount of use, and as a result, there is a risk of inflammation due to skin irritation. In addition, powdered sulfur is on the skin surface,
It also had the disadvantage that it produced so-called roughness and was not easy to use.

[Means for Solving the Problems] As a result of research conducted by the present inventors in order to eliminate such drawbacks, the present inventors found that using a reaction product of retinoic acid or retinol with sulfur as an active ingredient eliminates the above-mentioned drawbacks. It was discovered that an effective skin application material could be obtained, and the present invention was completed.

That is, the present invention is a skin application material containing at least one of the following as an active ingredient.

A, reaction product of retinoic acid and sulfur.

B, reaction product of retinol and sulfur.

C, reaction product of retinoic acid, retinol and sulfur.

The skin application material of the present invention is applied to the skin as an external skin preparation, such as an ointment, or as a skin cosmetic, such as a cream, or a scalp material. In particular, this product is extremely useful as a skin application material since it is effective in preventing, treating, and treating acne when applied to the skin, and it is extremely effective in preventing dandruff when applied to the scalp.

Furthermore, although retinoic acid or retinol has been known to have a keratin exfoliating effect, it has been rarely used because it is too irritating to the skin. However, the compound with sulfur according to the present invention has significantly improved skin irritation.

The present invention is also of great value in that it can effectively utilize the excellent exfoliating action of retinoic acid or retinol.

The chemical name of retinoic acid used in the present invention is 3,7-dimethyl-9-(2,6,6-1□limethyl-1=cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid, It has the following structure.

Moreover, retinol used in the present invention has the following structure.

Both have a keratin exfoliating effect, and retinoic acid is included in a small number of clinical acne drugs in the United States and other countries.

The skin application material of the present invention comprises one or more of the above-mentioned reaction product of retinoic acid or retinol and sulfur, or the reaction product of retinoic acid, retinol and sulfur.

The reaction is carried out between retinoic acid or retinol and sulfur, or a mixture of retinoic acid and retinol and sulfur, usually at 130 to 220°C, preferably at 15 to 150°C, in the presence or absence of a catalyst. Retinoic acid or retinol or a mixture of retinoic acid and retinol 10
Sulfur is usually used in an amount of 0.1 to 150 parts by weight, preferably 0.5 to 50 parts by weight.

The reactants are mainly those produced by a crosslinking reaction with sulfur at the unsaturated bond sites of retinoic acid or retinol, but may also contain other sulfurized reactants, such as mercapto compounds, and even unreacted products.

For example, the reaction product obtained by reacting 80 parts by weight of retinoic acid with 20 parts by weight of sulfur is a brown solid (at room temperature), and this product can be analyzed by GPC (gel filtration chromatography), NMR (nuclear magnetic resonance), mass spectrometry, infrared As a result of spectroscopy, we found that a cross-linked reaction product had two molecules of retinoic acid bound to each other by sulfur at the double bond site, a cross-linked reaction product had three molecules of retinoic acid bound to each other, and a cross-linked reaction product had four molecules of retinoic acid bound to each other at the double bond site. It was confirmed that it also contained unreacted substances.

The reactant in the present invention, unlike powdered sulfur, has the property of being dissolved in ethanol, solubilized or emulsified by various surfactants, and has antioxidant ability against oily components such as olive oil.

The skin application material of the present invention contains the above-mentioned reactant as an active ingredient, and contains other usual ingredients. Typical ingredients include oil, water, emulsifiers, humectants, powders, thickeners, antioxidants, preservatives, fragrances, and the like.

Regarding the amount relationship, the total amount of reactants of active ingredients is 10
0601 to 20, preferably 0.1 to 1 per 0 parts by weight
O parts by weight.

[Effects of the Invention] Unlike powdered sulfur, in the skin application material of the present invention, most of the sulfur is involved in the expression of medicinal or cosmetic effects, and therefore the amount of sulfur is small and there are no side effects such as skin irritation. It does not cause irritation or roughness on the skin, and has a good feeling of use. And surprisingly,
The skin preparation of the present invention can be used on the scalp to significantly prevent dandruff, acne, etc. When the skin application composition of the present invention contains an oily component, the quality does not deteriorate due to oxidative denaturation of the oil. Furthermore, the skin irritation of retinoic acid or retinol is significantly alleviated.

Next, we will discuss the dandruff prevention effect.

The preventive effect on dandruff was determined based on the results of use tests on rabbits and humans.

fl, l Use on rabbits Rabbits were used as test animals.
A 0% methanol 7'8 solution was applied. After applying oleic acid, a methanol solution of a retinoic acid-sulfur reactant at a predetermined concentration was applied to the outside of one ear wing.

This operation was performed once a day for a total of 4 days. Dandruff-like substances were formed in the ear wings to which only oleic acid was applied, whereas dandruff was formed in the ear wings to which oleic acid and the retinoic acid-sulfur reactant were applied, in proportion to the concentration of the retinoic acid-sulfur reactant. The formation of a similar substance was no longer observed.

The results are shown in Table (1).

(Margin below) Table fi+ [Formation of dandruff-like substance] (Note 1) +: Formation of nickel substance is observed.

±: Formation of nickel substance is hardly observed.

m: No formation of dandruff-like substance is observed.

(Note 2) No. 5 is a comparative example (2) Human use test As shown in the table (2) below, shampoos and hair tonics containing retinoic acid-sulfur reactants and retinol-sulfur reactants were prepared to prevent dandruff. We examined the effects.

Forty men with dandruff between the ages of 22 and 39 were selected as subjects, and tests were conducted on a total of 40 men, 10 for each sample.

The shampoo sample was used once when washing the hair, and the hair tonic sample was used only once after washing the hair.The amount of dandruff before the start of the test was compared with the amount of dandruff on the second day of hair washing at the end of the one-month test, and the amount of dandruff at the end of the test was compared. If the amount of dandruff is small, it is considered to be effective in preventing dandruff.
If the amount of dandruff did not change or if it increased, it was determined that there was no dandruff suppressing effect.

The head was suctioned using a vacuum cleaner, and the protein content of the collected dandruff was measured, and the results shown in Table (2) below were obtained.

Table (2) Furthermore, the therapeutic effects on acne will be described. Acne is
It is said that the secretory activity of the sebaceous glands increases and keratinization occurs in the pores, causing them to become clogged.

Furthermore, it is said that the cause of inflammation is the stimulation of free fatty acids produced when sebum is decomposed by P. acnes. Therefore, currently, in the treatment of acne, disinfectants that have a bactericidal effect against acne bacteria and exfoliation that opens pores are often used.

Therefore, in order to confirm the effectiveness of the product of the present invention against acne, the keratin exfoliating effect was investigated.

(1) Bactericidal test against acne bacteria Propionibacterium ac
nes, isolated from our laboratory, approximately 5 x 108 cells
/mQ) was mixed with the sample in phosphate buffer (pH 7,0). At this time, since the sample retinoic acid-sulfur reactant or retinol-sulfur reactant is insoluble in water,
% of Tween 80 was added and the test was conducted in a dispersed state.

After 60 minutes, 0.1- was sampled and diluted to 1/100 times. The L&CAM agar plate medium (Nissui Pharmaceutical Co., Ltd.) was inoculated with 0.1- of the bacteria, and incubated at 37°C for 4 hours.
The cells were cultured anaerobically for 1 day. The number of viable bacteria in the resulting colony was measured, the ratio to the number of viable bacteria when the sample concentration was θ% was calculated, and the killing rate was determined from that value to compare the bactericidal effects of each sample. The results were as shown in Table (3) below.

(Margins below) Table (3) (Note) Positive 1 and Positive 6 are Comparative Example (2) Keratin exfoliation test The test was conducted using dansyl chloride, which specifically binds to stratum corneum, as a marker.

5% Danzyl chloride (base, white petrolatum) 100
Apply a thin layer of μl onto a punch test bandage (1 cm in diameter) and apply this to a hairless mouse (♀ weight 10-20 g).
After occlusive application was applied to the backs of 25 animals for 24 hours, the stratum corneum was fluorescently stained. Next, 50 μl of each sample at various concentrations was applied to the fluorescent area once a day. The end point of the judgment was the day when the fluorescence of the existing stratum corneum disappeared under long wavelength ultraviolet rays in a dark room, and the exfoliation effect of the sample was measured by the number of days required for the fluorescence to disappear (average of 25 animals). The results were as shown in Table (4) below.

(Hereinafter in the margins) Table (4) (Hereinafter in the margins) From the results in Table (4), it can be seen that in the case of the invention example, the number of days required for the fluorescence to disappear is shorter than in the comparative example, and the exfoliation that opens the acne-affected area is effective. It can be seen that this treatment occurs quickly, and therefore has an excellent therapeutic effect on acne.

As is clear from the above, the skin application material of the present invention has excellent dandruff prevention effects and acne treatment effects.

[Example] Examples and synthesis examples of the present invention are shown below.

Example 1 (Manufacture of emulsion) Component (A) Amount (wt%) Setanol 1.5 Stearic acid
1.0 palmitic acid
0.5 Liquid Lanolin 1.
0 Squalane 2.0 Isopropyl myristate 1.0 Glyceryl monostearate 1,5 Tween 20 0.5 Retinoic acid - 10% sulfur reactant 0.5 Preservatives and fragrances Proper amount (B) ingredient Propylene glycol 3.0 Polyethylene Glycol 400 2.0 Triethanolamine 1.0 N Blue Ice Making
84.5 The components of (A) above were mixed to obtain a mixture.

Separately, a mixture (B) was obtained in the same manner. The mixture of (A) and the mixture of (B) were individually heated and dissolved at 70°C, and (
The mixture of A) was added to the mixture of (B) and emulsified using an emulsifier, followed by heat exchange and cooling to produce a milky lotion.

This emulsion was highly effective in treating acne and preventing dandruff.

Example 2 (Manufacture of cream) Ingredients (A) Amount (wt%) Cetano 4.0 Stearin M
'2.0 Vaseline
4.0 liquid paraffin
10.0 Isopropyl myristate 5.
0 Glyceryl monostearate 3.0 Retinoic acid - 20% sulfur reactant 1.0 Component (B) Glycerin 5.0 Propylene glycol 5.0 Potassium hydroxide
0.2 oval water
6o, 8A cream was produced in the same manner as in Example 1.

This product also showed remarkable efficacy in treating acne and preventing dandruff.

Example 3 (Manufacture of cream) (Ingredients A> Blending amount (wt%) Cetanol 4.0 Stearin r!1
) 2.0 Vaseline 4.0 Liquid paraffin 10.0 Isopropyl myrisudate 5.0 Glyceryl monostearate 3.0 Retinol - 20% sulfur reactant 1.5 Component of (B) Glycerin 5.0 Propylene glycol 5.0 potassium hydroxide
0.2 Purified water
60.3 A cream was prepared in the same manner as in Example 1. This product also showed remarkable efficacy in treating acne and preventing dandruff.

Example 4 (Cream detergent) Ingredients (A) Amount (wt%) Stearic acid 6.0 Palmitic acid
10.0 myristic acid
10. .

Lauric acid 8.0 Glyceryl monostearate 2.0 Glycerin 20.0 Propylene glycol 10.0 Retinoic acid - 20% sulfur reactant 0.5 Fragrance Appropriate amount (B) component Potassium hydroxide 7. OIi ice making
26.5 A creamy cleansing product (material for scalp application) was produced in the same manner as in Example 1. This product was highly effective in preventing dandruff.

Example 5 (Oint) Ingredients Amount (wt%) Solid paraffin 10.0 piece wax
l000 squalane
10.0 Retinoic acid - 10% sulfur reactant 1.0 Fragrance Appropriate amount Vaseline
69.0 The above bottoms were mixed, and the mixture was heated and dissolved at 80°C, and then cooled with stirring to obtain an ointment. This product was highly effective in treating acne.

Example 6 (Shampoo) Ingredients Amount (wt%) Sodium polyoxyethylene (2) Lauryl ether sulfate 25.0 Coconut oil fatty acid ethanolamide 5.0 Retinoic acid - 20% sulfur reactant 0.5 Preservative/Fragrance Appropriate amount of purified water
69.5 A shampoo was obtained in the same manner as in Example 6. This product was applied to the scalp and showed remarkable effectiveness in preventing dandruff.

Example 7 (Rinse) Ingredients (A) Amount (% by weight) Setanol 2.0 Glyceryl monostearate 3.0 Retinoic acid - 20% sulfur reactant 1.0 Preservative/Fragrance Appropriate amount Ingredient (B) Chloride Stearyltrimethylammonium 2.5 Propylene glycol 7.0 Purified water
84.5 A rinse was obtained in the same manner as in Example 1. This product also showed remarkable efficacy in preventing dandruff when applied to the scalp.

Example 8 (Hair Tonic) Appropriate amounts of Retinoin M-20% sulfur reactant 0.5 g, Nisocol HC0-60, 1.0 g, and perfume were dissolved in 55 g of ethyl alcohol at room temperature to obtain an alcohol phase. Separately, 1.0 g of glycerin and appropriate amounts of the pigment were dissolved in 42.5 g of purified water under heating and cooled. The alcohol phase was added to the obtained aqueous phase to solubilize it to obtain hair tonisoku.

This product was applied to the scalp and showed remarkable effectiveness in preventing dandruff.

Synthesis Example 1 (Synthesis of retinoic acid-20% sulfur reactant)
20 g of sulfur powder was added to 80 g of retinoic acid, and the reaction was carried out at 150 to 160° C. for about 2 hours under a nitrogen stream to obtain a brown solid.

Synthesis Example 2 (Synthesis of retinoic acid-10% sulfur reactant)
Synthesis Example 1 by adding log sulfur powder to 90 g of retinoic acid.
A brown solid was obtained in the same manner as above.

Synthesis Example 3 (Synthesis of retinol-5% sulfur reactant) 5 g of sulfur powder was added to 95 g of retinol, and a brown solid was obtained in the same manner as in Synthesis Example 1.

Synthesis Example 4 (Synthesis of retinol-20% sulfur reactant) 20 g of sulfur powder was added to 80 g of retinol, and a brown solid was obtained in the same manner as in Synthesis Example 1.

Claims (1)

[Claims] (1) A skin preparation containing at least one of the following as an active ingredient. A, reaction product of retinoic acid and sulfur. B, reaction product of retinol and sulfur. C, reaction product of retinoic acid, retinol, and sulfur.