JPH05105621A - Beautifying cosmetic comprising cinnamic ester derivative as active ingredient - Google Patents

Abstract

PURPOSE:To obtain a beautifying cosmetic capable of treating and improving stain, freckle and pigmentation site of skin after suntan and returning the site to a normal color of skin by locally applying the cosmetic to the site, having excellently improving effects on skin pigmentation. CONSTITUTION:The objective cosmetic contains preferably 0.01-50wt.%, especially 0.1-20 trans-o or p-dihydroxycinnamic acid of the formula (R is lower alkyl, preferably methyl, ethyl, propyl, especially ethyl) as an active ingredient, having the above-mentioned effects different from those of conventional sun- screening agents for previously preventing suntan, not being observed to develop irritation and allergy to skin thus having high safety. A dose is 1-20mg in the case of cream or ointment preparation and preferably 1-10mg in the case of liquid preparation.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a whitening cosmetic composition containing a trans-o, p-dihydroxycinnamic acid ester derivative as an active ingredient, which is safe and has an excellent pigmentation improving effect.

[0002]

2. Description of the Related Art Stain, freckles and pigmentation after sunburn are less likely to occur, increase or disappear with ageing, which is a problem for the skin of middle-aged and older people. Although the mechanism of the onset of these pigmentation disorders has not been clarified yet, it is considered that the melanin synthesis function in epidermal melanocytes is enhanced by the action of sunlight, particularly ultraviolet rays, and melanocyte-stimulating hormone. In addition, delayed keratinization with aging of epidermal keratinocytes (keratinocytes) also delays the rate of excretion outside the epidermis, and together with the enhancement of melanin synthesis ability,
It is considered that an increase in melanin granule density in the epidermis, that is, a symptom of clinically increasing pigmentation is manifested. Furthermore, because these pigmented areas are locally present and are clearly different from the surrounding normal skin color, the result is that the mechanism that controls the local melanin synthesis enhancement of melanocytes or the melanin synthesis of melanocytes is modulated. You might also say that.

There is a strong demand for a drug that restores these acquired pigments, that is, the melanin deposits to a normal skin color, and many drugs have been developed and commercialized. For example, in recent years, cosmetics using a vitamin C (L-ascorbic acid) derivative having an excellent reducing ability have been used, but it is difficult to be stable and almost no effect is observed when used externally. Met.

On the other hand, in Europe and America, hydroquinone is used as a drug 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. In some cases, there is a problem in that it is compounded as a drug. Various other melanin inhibitors have been reported, but as a cinnamic acid derivative, p-hydroxycinnamic acid (Bru
n, J. Soc. Cosmet. Chem., 25, 61 (1974)) and p-hydroxycinnamic acid amide derivative (JP-A-62-56459). However, at present, no substance is known that sufficiently satisfies both the pigmentation improving effect and the safety to the skin.

[0005]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a whitening cosmetic which is safe and has an excellent pigmentation improving effect.

[0006]

[Means for Solving the Problems] As a result of intensive investigations by the present inventors to obtain a substance that reduces or eliminates pigmentation through research on the mechanism of melanin production, a specific cinnamic acid ester derivative has a melanin production inhibitory action. In addition, they have found that no irritation to the skin, no allergy is observed, etc., and have completed the present invention.

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

[0008]

[Chemical 2]

The present invention provides a whitening cosmetic composition containing a trans-o, p-dihydroxycinnamic acid ester derivative represented by the formula (wherein R represents a lower alkyl group) as an active ingredient.

Examples of the cinnamic acid ester derivative (1) used in the present invention include trans-o, p-dihydroxycinnamic acid methyl ester, trans-o, p-dihydroxycinnamic acid ethyl ester, trans-o, p- Preferred examples include dihydroxycinnamic acid propyl ester. A particularly suitable compound may include trans-o, p-dihydroxycinnamic acid ethyl ester.

The cinnamic acid ester derivative (1) can be synthesized according to the method described in the literature or in accordance with it, for example, by condensing o, p-dihydroxybenzaldehyde and (Wittig) reagent such as (carbetoxymethylene) triphenylphosphorane. Method, a method of condensing o, p-dihydroxybenzaldehyde and malonic acid in the presence of a base such as pyridine or piperidine to esterify the resulting compound (Berman, J. Am. Chem. Soc., 80, 4949 (1958 )) And the like.

In the whitening cosmetic composition of the present invention, the cinnamic acid ester derivative (1) can be blended alone or in combination of two or more, and the blending amount thereof is 0.
01 to 50% by weight, particularly 0.1 to 20% by weight are preferred.

The whitening cosmetic composition 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 such cosmetics.

The whitening cosmetic composition of the present invention may contain any component other than the cinnamic acid ester derivative (1) as long as the effect of the present invention is not impaired. Ingredients usually blended in, for example, purified water, ethanol, oily substances, moisturizers, thickeners, preservatives, emulsifiers, medicinal ingredients, powders, perfumes, emulsion stabilizers, pH adjusters, etc. .. Specifically, as the oil component, 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, and moisturizing agents include 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 and the like can be mentioned. Thickeners include carboxyvinyl polymer, carboxymethyl cellulose, polyvinyl alcohol, carrageenan, gelatin. Water-soluble polymer such as sodium chloride,
Examples include electrolytes such as potassium chloride, preservatives such as urea, methylparaben, ethylparaben, propylparaben, butylparaben, sodium benzoate, etc., and emulsifiers such as polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, Nonionic surfactants such as polyoxyethylene 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, and powders Is talc, sericite, mica, kaolin, silica, bentonite, vermiculite, zinc flower, mica,
Examples thereof include titanium mica, titanium oxide, magnesium oxide, zirconium oxide, barium sulfate, red iron oxide, iron oxide, ultramarine blue, and the like, and pH adjusting agents include buffers such as lactic acid-sodium lactate and citric acid-sodium citrate.
Also, as various active ingredients, allantoin, vitamin E
By adding acetate, glycyrrhizin, yoquinin, various plant extracts, etc., the effect of suppressing melanin can be improved. Further, by adding various ultraviolet absorbing substances, it is possible to obtain a cosmetic having both a sunburn preventing effect and a sunburn preventing effect.

The whitening cosmetic composition of the present invention is applied to the affected area such as inflammation of the skin due to ultraviolet rays, stains, freckles, and a pigmented area after sunburn to treat / improve the affected area to obtain normal skin. Can be returned to color. Generally, the dose is, for example, in the case of a cream or ointment type preparation,
1 to ²⁰ mg per cm ^{2 of} skin surface, the same for liquid formulations 1
It is preferably about 10 mg.

[0016]

EXAMPLES Next, the present invention will be described with reference to Reference Examples and Examples.

Reference Example 1 Synthesis of trans-o, p-dihydroxycinnamic acid ethyl ester:
5.0 g (36.2 mmol) of 2,4-dihydroxybenzaldehyde
Was dissolved in 230 ml of benzene, and at room temperature, 16.4 g (47.1 mmo) of (carbetoxymethylene) triphenylphosphorane
l) was added over 1 hour, and stirring was continued for 3 hours in that state. After distilling off benzene with an evaporator, the residue was purified by column chromatography (SiO ₂ , hexane / ethyl acetate = 1), recrystallized from water-ethanol, and white scaly crystals with a melting point of 166.0-167.5 ° C. As
5.0 g of trans-o, p-dihydroxycinnamic acid ethyl ester (2
4.0 mmol) was obtained (yield 66%). IR (KBr, cm ^-1 ) 3348 (s), 3048, 2996, 2908, 1676 (s), 1610 (s), 1524,
1464, 1376, 1300 (s), 1254 (s), 1186, 1100, 1042, 98
8, 976, 866, 838, 818, 808,752, 646, 632, 544, 464 ¹ H-NMR (DMSOd ₆ , TMS, δ) 10.11 (1H, brs), 9.92 (1H, brs), 7.79 (1H, d , J = 16.0Hz),
7.42 (1H, d, J = 8.5Hz), 6.38 (1H, d, J = 16.0Hz), 6.38 (1H,
d, J = 1.7Hz), 6.29 (1H, dd, J = 8.5Hz, J = 1.7Hz), 4.15 (2H, q,
J = 7.0Hz), 1.24 (3H, t, J = 7.0Hz)

Example 1 Cosmetic lotion: (composition) trans-o, p-dihydroxycinnamic acid ethyl ester 5.0 (wt%) glycerin 4.0 polyoxyethylene hydrogenated castor oil 1.5 ethanol 10.0 sodium pyrrolidonecarboxylate 2.0 fragrance micropurification Total water remaining 100.0

Example 2 Oil Essence Type Cosmetic: (Composition) trans-o, p-dihydroxycinnamic acid ethyl ester 5.0 (wt%) mink oil 55.0 wheat germ oil 40.0 total 100.0

Example 3 W / O type moisturizing cream type cosmetic composition: (Composition) trans-o, p-dihydroxycinnamic acid ethyl ester 5.0 (% by weight) Vaseline 6.0 Cholesterol 0.6 Cetanol 0.5 Sorbitan sesquioleate 2.0 Liquid lanolin 4.0 Isopropyl palmi Tate 8.0 Squalene 10.0 Solid paraffin 4.0 Butylparaben 0.1 Methylparaben 0.1 Glycerin 3.0 Perfume 0.2 Purified water Balance total 100.0

Example 4 O / W type moisturizing cream type cosmetic composition: (Composition) trans-o, p-dihydroxycinnamic acid ethyl ester 5.0 (% by weight) Stearic acid 2.0 Cetanol 4.0 Vaseline 5.0 Squalene 8.0 Hardened palm oil 4.0 Polyoxy Ethylene sorbitan monostearate (20E.O.) 1.4 Lipophilic glycerin monostearate 2.4 Butylparaben 0.1 Methylparaben 0.1 Glycerin 3.0 Dipropylene glycol 3.0 L-Arginine 10.0 (%) Potassium hydroxide 0.2 Perfume 0.2 Purified water Balance 100.0 Total

Example 5 Emulsion type cosmetic composition: (Composition) trans-o, p-dihydroxycinnamic acid ethyl ester 5.0 (% by weight) Stearic acid 1.0 Cetanol 2.0 Vaseline 2.5 Squalene 4.0 Hardened palm oil 2.0 Polyoxyethylene sorbitan monostearate (20E.O.) 1.4 Lipophilic glycerin monostearate 1.2 Butylparaben 0.1 Methylparaben 0.1 Glycerin 3.0 Dipropylene glycol 3.0 Potassium hydroxide 0.2 Carboxyvinyl polymer 0.2 Perfume 0.2 Purified water Balance 100.0

Example 6 Pack-type cosmetic (paste peel-off type): (Composition) trans-o, p-dihydroxycinnamic acid ethyl ester 10.0 (wt%) Polyvinyl alcohol 12.0 Sodium carboxymethyl cellulose 3.0 Dipropylene glycol 2.0 Glycerin 2.0 Ethanol 5.0 Olive oil 3.0 Polyoxyethylene hydrogenated castor oil (30E.O.) 0.5 Titanium oxide 8.0 Kaolin 6.0 Perfume 0.1 Methylparaben 0.1 Purified water Balance 100.0

Example 7 Ointment Cosmetic: (Composition) trans-o, p-dihydroxycinnamic acid ethyl ester 10.0 (wt%) white petrolatum 90.0 total 100.0

Example 8 Liquid Cosmetic: (Composition) trans-o, p-dihydroxycinnamic acid ethyl ester 5.0 (wt%) ethanol 95.0 total 100.0

Test Example 1 Evaluation by tyrosinase activity of mouse dorsal skin hair follicle organ culture system Test method: 8 to 11 after birth, in which melanin synthesis is actively carried out
The dorsal hair follicles of C57BL mice for 3 days were cultured for 3 to 4 days.
The evaluation sample was added to the culture solution during culturing so that the final concentration was 5 mM, and the enzyme responsible for melanin synthesis, tyrosinase activity, was released from 3,5- ³ H-tyrosine to release tritium ( ³ HOH).
Was evaluated by comparing with the control. The results are shown in Table 1. No suppression effect 0-5% ± 5-35% +35%-++ Result:

[0027]

[Table 1]

Test Example 2 A brown guinea pig having an acquired ability to form melanin pigment spots was used as an experimental animal, and after pigmentation was formed, the effect of improving fading on pigmentation was examined. Test method: Using a brown guinea pig (a guinea pig whose skin color is similar to that of a human race of yellow color, pigmented spots start to appear about 4 days after irradiation of ultraviolet rays like humans, and turn black most in about 8 days).
The back hair of the guinea pig was shaved with a hair clipper and then shaved with an electric razor. After 8-methoxypsoralen (PUVA) was intraperitoneally administered to this guinea pig, UVA (BLB lamp, 3.1 m
W / cm ² ) was irradiated for 5 minutes. PUV generated from 15 days after irradiation
A sample (trans-o, p-dihydroxycinnamic acid ethyl ester) 5% solution (ethanol 80
%, Water 20%) was applied twice a day continuously for a total of 30 days. The degree of blackening of the skin color was visually evaluated according to the following criteria, and the evaluation points were averaged to measure the effect. The results are shown in Table 2. Criteria 0: No pigmentation is observed. 1: A slight pigmentation with unclear boundaries is observed. 2: Medium pigmentation with clear boundaries is recognized. 3: Clearly marked strong pigmentation is observed. result:

[0029]

[Table 2]

[0030]

EFFECTS OF THE INVENTION The whitening cosmetic composition of the present invention has an excellent pigmentation improving effect and is different from the conventional sunscreen agents etc. which prevent sunburn in advance, and is locally applied to the spots on the skin, freckles, and the pigmented portion after sunburn. It is possible to treat and improve the area and restore the normal skin color by applying Further, the active ingredient trans-o, p-dihydroxycinnamic acid ester derivative (1), irritation to the skin, the development of allergies, etc. are not observed, the whitening cosmetic composition of the present invention is highly safe ..

Claims (1)

[Claims] 1. A general formula (1): (Wherein R represents a lower alkyl group)
A whitening cosmetic composition containing an so, p-dihydroxycinnamic acid ester derivative as an active ingredient.