JPS59157009A - External skin drug for suppressing formation of melanin - Google Patents

Abstract

PURPOSE:To provide an agent effective to prevent the chloasma and to beautify the skin, by compounding a tyrosinase-inhibitor such as beta-thujaplicin, hydroquinone, pyrone compound, etc. with an adsorbent of melanin pigment, preferably a hydrated aluminosilicate adsorbent supported on a reducing substance. CONSTITUTION:The titled agent prepared in the form of ointment or cream, is obtained by compounding (A) a tyrosinase-inhibitor such as beta-thujaplicin, hydroquinone, pyrone compound, etc. (preferably hydroquinone-beta-thujaplicin or hydroquinone-pyrone compound) with (B) a melanin-adsorbent (preferably a hydrated aluminum silicate adsorbent supported on a reducing substance). The above preparation may contain other additives such as non-enzymatic inhibitor for oxidation and polymerization of dopa, inhibitor for the sun-tan effect of ultraviolet radiation (e.g. vitamin C), inhibitor for generation of active oxygen, agent for removing active oxygen, a keratolytic agent (e.g. urea), etc. The obtained drug suppresses the formation of melanin responsible for chloasma and freckles.

Description

[Detailed description of the invention]

The present invention is an ointment that suppresses the increase in melanin formation that is within 1 of liver spots and sparrow spots, prevents the linkage effect of ultraviolet rays, and reduces the formed melanin pigment to fl12 (Q) to create fair and beautiful skin. Or related to creams.Melanogenesis has not been completely investigated.

[) I don't know, but is there almost a summary of the process and the existence of the three processes in the Book of Books? There is a consensus among TLL researchers. 1) Dirosin → Dopa・・・Excellent Dopa o −l
The process leading to the formation of x (catalyzed by tyrosinase)
2) Dopachrome...A polymerization process that involves oxidation reactions that do not involve enzymes that lead to melanin. 3) The melanin production process involves active oxygen (5uperoxi+Ia).
s) It is said that the process of oxidation into Pl is involved. Therefore, to suppress melanin formation, (a)
U inhibition, (1"1) Inhibition of active oxygen generation, removal of active oxygen, (c) Ultraviolet blocking, (d) Inhibition of oxidation reaction, (e) Inhibition of polymerization process, (f) Decomposition of produced melanin, (1-
) Possible causes include melanin adsorption. As is well known, melanin pigment is present in the basal layer of the skin.
7γ1g melanin 1~U is formed, migrates to corneocytes, and is lost to the outside of the body without exfoliation of keratinized cells. is defined by the creation-disappearance equilibrium. Tree inventor number, 1
Note on this point: I invented a strong adsorbent for melanin pigment. The features of the present invention (b)--, which can be called the fundamental features, are:
Melanin production involves many processes, each of which undergoes many attacks. Therefore, it is a feature of the present invention that a variety of drugs are used and their synergistic effects can be clearly avoided. Currently, C is also suppressing melanin production (Ni, J, A), anti-II+', 11, whitening effect A, "I'm not sure if it's 4F or 1], 1 father ~ 1
? J, Su, Strong Kai 1
As a result of using drugs or high-temperature drugs, fatal side effects can be avoided. The fundamental features of the present invention can be summarized as above. (1) There are various attack points for suppressing the melanin production process, and various attack methods produce synergistic effects, which attenuate the side effects caused by focusing on each attack. (2) ) The equilibrium between production and disappearance of melanin pigment is avoided by shifting towards disappearance by using an adsorbent. The above principle will be explained in detail below. Among them, hydroquinone and its derivatives are famous as those that have been used clinically. In conclusion, high ff+f[(4-6%
) Long-term use of hydroquinone has a clear skin-lightening effect, but it is accompanied by side effects such as vitiligo, making it impossible to use. It is said that there are no side effects when using 2% C of Hyde[+-tnon, but the effects are not clear either. . Different from the reducing agent hydroquinone, the harmful effect of β-tupridine on dirosypyl L'111 and the inhibitory effect of pyrone compounds are completely different from the reducing effect. The idea of the present invention is that 1 of hydroquinone β-A7 bricine
11, hydroquinone and the vinyl compound U(U) showed a synergistic effect with the harmful effects of B[1Sino-L'1M+!, 2. There is a synergistic effect between pyrone compounds such as pridine, which are not effective or have only mild effects when used alone. There is no effect,
Only an additive effect is seen. Example 1 (each of β-tuvridine and hydroquinone,
and combination tyrosinase inhibitors) Pine Shroom Chi [''Cina-I! (manufactured by Sigma) to measure dopachrome produced using tyrosine as a substrate (Pomerantz 1963)
According to the method. As the pyrone compound, pyrocomenic acid (PVrOCOIIlliC (LCid) was used. Pyrone compounds such as maltol, edylmaltol, human f]ximaltol, and tudic acid are all found to have some degree of tyrosinase inhibitory effect, and similar synergistic effects are observed. The experiments and results are summarized in Table 1. 5or)) is 20.2-t21]1→l
-12021-02 is an enzyme that catalyzes the reaction, and glulimine salt inhibits the generation of 02 through photochemical reactions. The combination of these substances with different mechanisms of action is meaningful. Glu-1 limine is unstable and cannot be used, and glucosamine hydrochloride cannot be expected to have long-term stability.
It would be better to use Il-Gulni 14nomin etc.'). Glucosamine is also known to inhibit melanosome formation. I-(+3) Active acid-based remover The active oxygen removal effect was determined by the pyrogallol autoxidation method (S, Ma
rklund a+ol G, Marklund
d, [or. J, Biocl+em, (1974) AJ-, 4
69) Do-5-hydroxydopamine autoxidation method (R,F
. II cikki Ia and F, Ca
old] a[, Δnalyt. Biocl+em, (1976) 75, 356), American: 1 lupic acid and cysteine (cys+c
i++e: C3f17N O2S) derivative was the strongest. Example 2 (Active oxygen removal effect) Pi[! Gallol autoxidation method and 5-human oxide. The active oxygen scavenging effects of Pamine autoxidation method, Cysteine derivatives, )l-lupic acid, etc. were measured. The experimental results are summarized in Table IV. (2) Dopa oxidation and polymerization inhibitor Many reducing substances can inhibit the melanin formation reaction using dopa as a starting material, but I-cysteine derivatives and ascorbic acid had the strongest effect on eight of them. Example 3 (Suppression effect of reducing agent) Dopa 0.5% glue/v IIQ buffer solution (pl
-17,0) Blow air for 31-1 hours/v (Measure the resident melanin (measure 470ml Il'c absorbance 1 good), set the target of 11 harmful substances to 100% - ,6
(See Table V to calculate the 11 harm in % for each harmful substance.) When carried out under ultraviolet irradiation, melanin formation can be observed in 3 hours. using a high-pressure mercury lamp with a strong line spectrum between 365 and 579.1 h;
Melanin formation in 0.5% DOPA phosphate buffer solution was measured at an absorbance of /170ml (see Table v1). Although the inhibitory effect of cysdin derivatives was eliminated,
The vinyl compound, asnirudic acid also showed a clear inhibitory effect. (2) Melanin decomposing agent example 5 (Melanin decomposition ability) It was discovered that substances that decompose melanin include oxidizing agents such as hydrogen peroxide and soda percarbonate, and reducing agents such as cysteine and geltade A>. However, the oxidizing agent is used in the polymerization process G,
li! It is not preferable because it has a progressive effect. The melanin-adsorbing effect of reducing agents is strongest in cydes and innes (Table ■
reference). A cysdine derivative was added to a 0.01% melanin solution ('llN6.2), and the decomposition of melanin was investigated at an absorbance of 470 mμ. The experimental results are summarized in Table V■. V+, Melanin Adsorbent Through the research of the present inventor, it was proven that various natural silica-alumino compounds have a melanin-adsorbing effect. Various melanin adsorbents have been synthesized. Among them, the adsorption capacity of hydrated silica/alumina supporting reducing substances was the highest. These adsorbents are insoluble in water and consist of particles of several microns, so they cannot be expected to penetrate deeply into the skin. Lilithylic acid was used. ■4 Ultraviolet absorber It is well known that sunlight causes thickening of the skin's keratin and promotes the production of melanin pigment. Therefore, it is extremely meaningful to use this method to eliminate the effects of sunlight. For this purpose, it is necessary to incorporate a UV absorber. Ultraviolet absorbers include para-aminobenzoic acid, zarydylic acid, cinnamic acid, pensiphenone, and azo.
system-compounds are known. Any of these C's may be used, but examples include canic acid, which is present in the epidermis of humans. Based on the above experimental results and theory, it is necessary to pay attention to melanin production 4.Hereinafter, we will show the knee 1) of the treatment 7j example J0 Example 1 (treatment/j example) Melanin production inhibition 11i11 Tato 11
1φ large? Tobi ingredient
Weight% urea 5-15] Noritylic acid 0-0.5 or sodium polylycylate 0-2.0 β-T\7 bricine 0.03-0.05 Hydroginone O, 2,0 pyronated content
0-2.5 cysteine hydrochloride
O~2.0 Ascorbic acid stearate 1-0・~
0.1 hypo () ~ 2.03
od, meLasulp former LeO ~ 0,053o
d, 5ull+hite anby+Irous
O~0.02 acylglu] limine
0~2.0soo o~appropriate E D T80~(1,0
5α-1~Coferol 0.05~0.1
Ingredient weight
Amount% urocanic acid 0-1.0 or more of the components that are water-soluble are dissolved in water, and the power - Bowax 4
Add 00-4-000 in an appropriate ratio, add fat-soluble ingredients, and finally add 5% melanin adsorbent and mix well. All operations are performed under a nitrogen stream, and the container is sealed from light and filled in an airtight container. Example 2 (formulation example) Melanin formation inhibiting topical cream Ingredients Heavy
Amount (%) Urea 5-10 Hyde 1-1 Quinone 1.0-. 20 Marutol 1.0 Cisphine hydrochloride 1.0 - 2.0 Purified water (appropriately exposed to dissolved air and replaced with nitrogen C) Nriribulic acid 0.2 β-Tsuoni 7
Bricine 0.03 Hyde 1] 1 Quinone
1.0 ingredient
Weight% 13 1] 1-8
0.0
3α-1-nee + Fe[1-le 0.1 Ascorbic acid Sudea 1 note 0.05 Glyrelin
The mixture is mixed with an appropriate amount of ream prepared under a nitrogen stream, and immediately filled in an airtight, light-shielding container. Below, the composition of the soft varnish and cream of the present invention is described below.
The effects and usage effects are shown in Table 1-Vll.

Claims (5)

[Claims] (1) Synase inhibitor, β-fluoride, melanin pigment adsorbent, ) 47+ reducing substance-supported hydrated aluminum silicate, cum adsorbent (patent application number 5)
6-90651) for the purpose of anti-hepatitis and whitening. (2) A non-enzymatic dopa oxidative polymerization N4 harmful agent and one or more of "C vitamin C, cysdine hydrochloride, cysdine derivatives, geltadeone" as a UV phosphorus 11JI harmful agent are roughly blended. Ointment and cream according to item 1. (3) The ointment and cream according to claim 1, which further contain one suitable substance among various substances having antiphosphorus burn and antiphosphorus effects. (4) The soft steamer and cream according to claim 1, which contain an active oxygen generating inhibitor and an active oxygen removing agent. (5) The ointment and cream 1\ according to claim 111'i, which further contain urea, lillibulic acid, or a salt thereof as a keratolytic agent.