JPH06321747A - Dermal medicine for external use - Google Patents

Abstract

PURPOSE:To obtain a stable skin care cosmetic excellent in improvement of spots, freckles and pigmentation of the skin after sunburn, etc., and exhibiting a high safety. CONSTITUTION:This dermal medicine for external use contains a p- hydroxyphenylpropanol derivative of the formula (R<1> is H or a lower acyl; R<2> and R<3> are each H, OH or a lower acyloxy; R<4> is H or a lower acyl ; Bond with dotted line shows single or double bond), e.g. 3-(p-hydroxyphenyl)-2-propen-1- ol as the active component. The mixture ratio of the compound of the formula is preferably 0.01 to 50wt.%, especially 0.1 to 20wt.% based on the whole composition. This dermal medicine for external use is used generally as a cosmetic preferably in the form of lotion, milky lotion, cream, ointment, stick, organic solvent solution, pack, gel, etc.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a skin external preparation having an excellent pigmentation-improving effect, more specifically, it strongly suppresses the activity of tyrosinase, and can improve the deposition of melanin pigment due to sunburn, etc., and The present invention relates to a skin external preparation with few side effects.

[0002]

2. Description of the Related Art Stain, freckles, and pigmentation on the skin after sunburn are less likely to occur, increase, or disappear with age, which is a problem for middle-aged and older people. Although the pathogenic mechanism of these pigmentation diseases has not been clarified yet,
It is considered that the melanin-synthesizing function in epidermal melanocytes is enhanced by the action of sunlight, especially ultraviolet rays, and melanocyte-stimulating hormone.

Further, it is considered that the delay of keratinization of epidermal keratinocytes (keratinocytes) with aging causes an increase in the density of melanin granules in the epidermis, that is, a clinically symptomatic increase in pigmentation. These pigmented areas are localized and may cause a clear difference with the surrounding normal skin color.

There is a strong demand for the development of a drug capable of restoring such an acquired pigment (ie, melanin) deposit to a normal skin color, and many drugs have been commercialized so far.

For example, in recent years, cosmetics containing a vitamin C (L-ascorbic acid) derivative having an excellent reducing ability have also been used. However, the vitamin C derivative has a problem in stability and almost no effect is observed when used externally.

[0006] On the other hand, in Europe and America, hydroquinone is used as a medicine for treating spots and whitening black skin, but this also has a problem in the safety (irritation and allergenicity) of the substance itself, and vitiligo. There is a problem in that it is mixed as a drug from the viewpoint that it sometimes causes Other various melanin inhibitors have been reported, for example, isoflavone derivatives (JP-A-58-2250).
No. 04), p-hydroxycinnamic acid (JP-A-59-1)
96813), p-hydroxycinnamic acid amide derivative (JP-A-62-56459), and the like.

However, at present, there is no known substance which is excellent in both the pigmentation improving effect and the compoundability in the base for external preparations.

[0008]

DISCLOSURE OF THE INVENTION The present invention provides a skin external preparation containing a compound having an excellent pigmentation-improving effect and having excellent performance in terms of mixability with an external preparation base. The purpose is to

[0009]

In view of the above situation, the present inventors have earnestly studied to obtain a substance that reduces or eliminates pigmentation through research on the mechanism of melanin production, and as a result, a specific p-hydroxyphenylpropanol was obtained. The inventors have found that the derivative has a melanin production inhibitory action and also has a good blending property with various bases, and completed the present invention.

That is, the present invention provides the following general formula (1)

[0011]

[Chemical 2]

(Wherein R ¹ is a hydrogen atom or a lower acyl group, R ² and R ³ are a hydrogen atom, a hydroxyl group or a lower acyloxy group, R ⁴ is a hydrogen atom or a lower acyl group, and the broken line is It also indicates that it may be a double bond.) The present invention relates to a skin external preparation containing a p-hydroxyphenylpropanol derivative represented by the formula (4) as an active ingredient.

In the general formula (1), the lower acyl group of R ¹ and R ^{4 and} the lower acyl group of the lower acyloxy groups of R ² and R ³ include an acyl group having 1 to 5 carbon atoms, for example, an acetyl group, Examples thereof include a propionyl group and a butyryl group.

Preferred specific examples of the p-hydroxyphenylpropanol derivative used in the present invention include 3-
(P-Hydroxyphenyl) -2-propen-1-ol, 1- (p-hydroxyphenyl) glycerol, 3
-(P-hydroxyphenyl) -1-propanol, 1
-(P-Hydroxyphenyl) -1,3-propanediol triacetate, 1- (p-hydroxyphenyl)
Examples include -1,3-propanediol and the like.

Some of the p-hydroxyphenylpropanol derivatives (1) are known as decomposed products of lignin, which is a polymer substance in timber (Mokuzai Gakkaishi, No. 1).
Volume 4, Issue 6, p. 328-355, 1968). However, their effect as a whitening agent has not been known.

The p-hydroxyphenylpropanol derivative (1) can be synthesized according to a conventionally known method, for example, Journal of the Wood Science Society, Volume 15, No. 6, p. 256
To 261 or a method similar thereto.

The external preparation for skin of the present invention may contain the above-mentioned p-hydroxyphenylpropanol derivative (1) alone or in combination of two or more kinds, and the compounding amount thereof is 0. 01-50% by weight, in particular 0.1-
20% by weight is preferred.

The external preparation for skin of the present invention can be made into various forms, but in general, it is generally in the form of lotion, emulsion, cream, ointment, stick, solution with organic solvent, pack, gel. It is preferable to use cosmetics such as

The external preparation for skin of the present invention may contain any component other than the p-hydroxyphenylpropanol derivative (1) within a range that does not impair the effects of the present invention. Ingredients usually added to external preparations, such as purified water, ethanol, oily substances, humectants, thickeners,
Preservative, emulsifier, medicinal ingredient, powder, fragrance, emulsion stabilizer,
A pH adjuster or the like can be added.

Specific examples of the oily component include liquid paraffin, petrolatum, paraffin wax, squalane, beeswax, carnauba wax, olive oil, lanolin, higher alcohols, fatty acids, synthetic ester oils of higher alcohols and fatty acids, silicone oils and the like. As the moisturizer, sorbitol, xylitol, glycerin, maltitol, propylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, polyoxypropylene fatty acid ester, polyethylene glycol, etc. Examples of the thickener include carboxyvinyl polymer, carboxymethyl cellulose, polyvinyl alcohol, carrageenan, water-soluble polymers such as gelatin, sodium chloride, potassium chloride. Electrolytes and the like, preservatives include urea, methylparaben, ethylparaben, propylparaben, butylparaben, sodium benzoate and the like, and emulsifiers such as polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene. Nonionic surfactants such as sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitol fatty acid ester, and the like, powder as talc, Sericite, mica, kaolin, silica, bentonite, vermiculite, zinc white, mica, titanium mica, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, benga , Iron oxide, include ultramarine blue, as a pH adjusting agent lactate - sodium lactate, citric acid - include buffering agents such as sodium citrate. Also, as various active ingredients, allantoin, vitamin E derivative, glycyrrhizin, ascorbic acid derivative, kojic acid, arbutin, pantethenic acid derivative, placenta extract, anti-inflammatory agent, yoquinin, various plant extracts, etc. are added to suppress melanin. The effect can be improved. Furthermore, by adding various ultraviolet absorbing substances, a skin external preparation having both a sunburn preventive effect and a therapeutic effect can be obtained.

The external preparation for skin of the present invention is applied to the affected area such as inflammation of the skin due to ultraviolet rays, stains, freckles, and pigmented area after sunburn to treat / improve the area and normal skin. Can be returned to color. Generally, the dose is, for example, in the case of a cream or ointment type preparation,
It is preferably 1 to 20 mg per cm ^{2 of the} skin surface, and 1 to 10 mg in the case of a liquid preparation, but it is not limited to this.

[0022]

EXAMPLES The present invention will be described in more detail below with reference to examples, but the present invention is not limited thereto.

Test Example 1 Evaluation of guinea pig dorsal skin hair follicle organ culture system by tyrosinase activity Test method: Meanin synthesis is actively carried out 8-1 after birth
One day brown guinea pig dorsal follicles were cultured for 3-4 days. The evaluation sample was added to the culture medium during culturing so that the final concentration was 5 mM, and the activity of tyrosinase, which is an enzyme responsible for melanin synthesis, was measured by the amount of tritium released from 3,5- ³ H-tyrosine ( ³ HOH). The results were evaluated by comparing with the control according to the following criteria. The results are shown in Table 1. No suppressive effect 0 0 to 5% ± 5 to 35% + 35% to ++ Result:

[0024]

[Table 1]

Test Example 2 Evaluation of the brown guinea pig dorsal skin hair follicle organ culture system by melanin synthesis activity Test method: 8 to 1 after birth, in which melanin synthesis is actively carried out
One day brown guinea pig dorsal follicles were cultured for 3-4 days. The evaluation sample was added to the culture medium during the culture so that the final concentration was 5 mM, and the melanin synthesis activity was measured by the amount of ¹⁴ C-thiouracil incorporated, and evaluated by comparing with the control according to the following criteria. The results are shown in Table 2. No suppressive effect 0 0 to 5% ± 5 to 35% + 35% to ++ Result:

[0026]

[Table 2]

Example 1 Pigmentation improving cream

[Table 3] (Components) (% by weight) (1) Decaglyceryl stearate 1.8 (2) Polyoxyethylene cetyl ether 1.2 (3) Squalane 12.0 (4) Cetanol 6.0 (5) Palmitin Cetyl acid 3.0 (6) 1,3-butylene glycol 6.0 (7) Glycerin 3.0 (8) 3- (p-hydroxyphenyl) -1-propanol 1.0 (9) Purified water residual amount ( 10) Fragrance A slight amount (manufacturing method) The oil phase components (1) to (6) are heated and mixed at 80 ° C., and the aqueous phase components (7) to (1) are heated to 80 ° C. under stirring.
0) is added and emulsified, and then cooled to room temperature with stirring.

Example 2 Emulsion for improving pigmentation

[Table 4] (Components) (% by weight) (1) Polyoxyethylene sorbitan stearate 1.0 (2) Glycerol oleate 1.0 (3) Glyceryl monostearate 0.5 (4) Squalane 6.0 ( 5) Glyceryl trioctanoate 2.0 (6) Cetyl octanoate 2.0 (7) Stearyl alcohol 2.0 (8) 1,3-Butylene glycol 5.0 (9) Glycerin 3.0 (10) 1- ( p-Hydroxyphenyl) -1,3-propanediol 0.5 (11) Purified water Remaining amount (12) Fragrance (manufacturing method) Oil phase components (1) to (7) are heated and mixed at 80 ° C. with stirring. Water phase components (8) to (1
After 2) is added and emulsified, the mixture is cooled to room temperature with stirring.

Example 3 Lotion for improving pigmentation

Table 5 (Components) (wt%) (1) 1,3-butylene glycol 8.0 (2) glycerin 4.0 (3) sodium hyaluronate 0.1 (4) ethanol 3.0 (5) poly Oxyethylene polyoxypropylene decyl tetradecyl ether 0.3 (6) 1- (p-hydroxyphenyl) glycerol 0.1 (7) Purified water residual amount (8) Fragrance (manufacturing method) (1) to (3) and After dispersing the component (6), 60% of the component (7) is added thereto to obtain A. On the other hand, after stirring and dissolving the components (4), (5) and (8), the remaining amount of the component (7) is added to this and designated as B. While stirring A, add B and mix.

Example 4 Serum for improving pigmentation

(Table 6) (Components) (wt%) (1) 1,3-butylene glycol 8.0 (2) glycerin 4.0 (3) xanthan gum 0.3 (4) sodium chondroitin sulfate 0.1 (5) hyalurone Sodium acid salt 0.05 (6) Ethanol 3.0 (7) Polyoxyethylene polyoxypropylene decyl tetradecyl ether 0.3 (8) 3- (p-hydroxyphenyl) -2-propen-1-ol 2.0 (9) Purified water Remaining amount (10) Perfume A trace amount (Production method) After stirring and dispersing the components (1) to (5) and (8),
To this, 65% of the component (9) is added to obtain A. On the other hand, after stirring and dissolving the components (6), (7) and (10),
The component (9) of the remaining amount is added to this and it is designated as B. While stirring A, add B and mix.

[0031]

The external preparation for skin of the present invention strongly suppresses the activity of tyrosinase, which is an enzyme required for melanin synthesis, and also suppresses the formation of melanin in artificially formed pigment spots. Moreover, it exhibits an excellent melanin deposition improving effect with almost no side effects.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Mitsutoshi Kimura 2606-6 Akabane, Kai-cho, Haga-gun, Tochigi 3-405 Kaisha's house, Kao-shi (72) Inventor Yukihiro Yada 1-chome, Kumeda-nishi, Ninomiya-cho, Haga-gun, Tochigi 115 − 1 (72) Inventor Genji Imokawa 1022-89 Himurocho, Utsunomiya City, Tochigi Prefecture

Claims (1)

[Claims] 1. The following general formula (1): (In the formula, R ¹ is a hydrogen atom or a lower acyl group, R ² and R ³ are a hydrogen atom, a hydroxyl group or a lower acyloxy group, R ⁴ is a hydrogen atom or a lower acyl group, and a broken line indicates a double bond. The external preparation for skin containing the p-hydroxyphenylpropanol derivative represented by the formula (1) as an active ingredient.