JPH04235112A - Tyrosinase-inhibitor - Google Patents

Abstract

PURPOSE:To obtain a tyrosinase-inhibitor usable as a skin-beautifying agent for cosmetic and an agent for preventing blackening and browning of food, etc., by using 1,3,5-trihydroxybenzene derivative as an active component. CONSTITUTION:The active component of the objective tyrosinase-inhibitor is the compound of formula I (R1 is H or glucose residue; R2 is H or group of formula II ; at least one of R1 groups is H but all of R1 and R2 groups are not H at the same time), e.g. phlorin of formula III, phloridzin of formula IV or phloretin of formula V. These compounds have remarkable tyrosinase- inhibiting activity comparable or superior to that of known agent such as kojic acid and arbutin. The amount of the compound is preferably about 0.5-1g per 100g of cosmetic in the case of using as a skin-beautifying cosmetic or 1-2g per 100l of solution in the case of using as a blackening preventing agent for food preferably in the form of an aqueous solution or an organic solvent solution.

Description

[Detailed description of the invention]

0001

FIELD OF THE INVENTION This invention relates to tyrosinase inhibitors. More specifically, the present invention relates to a tyrosinase inhibitor that contains a 1,3,5-trihydroxybenzene derivative as an active ingredient and can be used as a skin whitening agent, a blackening/browning inhibitor for foods, etc.

0002

Problems to be Solved by the Invention The stains, freckles, etc. that occur on human skin are mainly caused by the formation of melanin in tissues caused by sunburn, etc. The formation of melanin is also responsible for the blackening and browning of fresh foods such as seafood and fruits and vegetables.

[0003] Melanin is known to be formed by first enzymatically oxidizing tyrosine by tyrosinase, and then through several reaction steps.

[0004] Therefore, substances that effectively inhibit tyrosinase activity are extremely useful for use in skin whitening cosmetics, anti-blackening agents for foods, and the like.

[0005]

[Means for solving the problem] In view of the above background, the present inventors have searched for tyrosinase activity inhibitors and found that
General formula I below:

[0006]

[C6]

[In the formula, R1 each represents a hydrogen atom or a glucose residue, and R2 represents a hydrogen atom or a group]

000
8]

[C7]

[0009] However, at least one of R1 always represents a hydrogen atom, but all R1 and R2 do not represent hydrogen at the same time] We have discovered that a compound has remarkable tyrosinase inhibitory activity, and we have developed this invention. The invention was completed.

Therefore, the present invention provides the following general formula I

0011
]

[Chemical formula 8]

[In the formula, R1 each represents a hydrogen atom or a glucose residue, and R2 represents a hydrogen atom or a group]

001
3]

[Chemical formula 9]

[0014] A tyrosinase inhibitor containing a compound having the following formula as an active ingredient, provided that at least one of R1 always represents a hydrogen atom, but all of R1 and R2 do not represent hydrogen at the same time.

Examples of compounds having the above general formula are:
Examples include the following compounds.

[0016]

[Chemical formula 10]

The compounds exemplified above are all known compounds, but they were not known to have tyrosinase inhibitory activity.

[0018]

EXAMPLES The tyrosinase inhibitory activity of each compound was measured using various compounds of the above general formula I, ie, phlorin, phlorizin, and phloretin. Phlorizin and phloretin were sold as reagents by Wako Chemical Co., Ltd., and phlorin was produced from phlorizin in the following manner.

Preparation of Phlorin 1 g of Phlorin was mixed with 10% barium hydroxide aqueous solution 10
It was heated to about 100° C. for 30 minutes in 0 ml and hydrolyzed to produce florin. Under this condition, glycoside bonds are not hydrolyzed.

After neutralizing the reaction solution with dilute H2 HO4, the filtrate was dried and then purified by column chromatography on silica gel (Wako 200 mesh) (benzene:ethanol = 9:1). Florin is a pure white crystal with a melting point of 231-233° and a specific optical rotation [α]D 2
It was 2-74.58°.

Tyrosinase inhibition test A 0.05% aqueous solution of each compound was used as a sample, and the following test procedure was conducted.

20mg of tyrosine (0.3mg/ml)
, 20 ml of McIlvaine buffer (pH 6.8) and 0.6 g of agar were placed in an Erlenmeyer flask, stirred, heated to boiling, and then cooled to 45°C. When the temperature reached 45°C, tyrosinase solution (1 mg/ml) was added to Add 2 ml, stir, and transfer to a Petri dish to make an agar plate.
A paper disk (mm) was placed, and the diameter of the inhibition circle centered on the disk was measured to determine the tyrosinase inhibitory effect. At the same time, kojic acid and arbutin, which are known to have a large tyrosinase inhibitory effect, were also measured as controls. The results are shown in Table 1 below.

[0023]

[Table 1]

*After 24 hours, the water, arbutin, and kojic acid paper discs had turned blackish brown, but the florin, phlorizin, and phloretin paper discs remained white.

[0025] Using the same sample as above, 1 ml of the sample was added to 10 ml of tyrosine solution (30 mg/200 ml), 10 ml of McIlvaine buffer (pH 6.8), and 20 ml of distilled water, and after incubation at 37°C for 10 minutes, Add 0.1 ml of tyrosinase solution (15 mg/15 ml, Sigma), stir with a stirrer,
Absorbance was measured every 30 minutes at 0 nm to measure melanin production. Ascorbic acid and arbutin were used as controls. The results are shown in Table 2 below.

[0026]

[Table 2]

A graph in which the absorbance obtained for each sample is plotted against time is shown in FIG.

As can be seen from the above results, the compound of formula I of the present invention has a tyrosinase inhibitory activity equivalent to or higher than that of kojic acid, arbutin, etc., which have been known to have tyrosinase inhibitory activity. Therefore, it is extremely useful for use in whitening cosmetics, anti-blackening agents for foods, etc.

The whitening cosmetic containing the tyrosinase inhibitor of the present invention can be produced in an appropriate form such as a cream, milky lotion, lotion, etc. by a conventional method using conventionally used cosmetic base materials. In addition, the whitening cosmetics include ultraviolet absorbers, ultraviolet scattering agents, other medicinal ingredients, thickeners, plasticizers,
Any known additives such as colorants and fragrances can be contained.

When the tyrosinase inhibitor of the present invention is used in whitening cosmetics, it is preferably used in an amount such that about 0.5 to 1 g of the compound of general formula I is contained per 100 g of the cosmetic.

When the tyrosinase inhibitor of the present invention is used as a blackening inhibitor for foods, it is preferably used as an aqueous solution of the compound of the above general formula I or as a solution in a suitable organic solvent. It may contain additives. When used as an anti-blackening agent for foods, solution 100
It is preferable to use an amount such that 1 to 2 g of the compound of the above general formula 1 is contained per 1 liter of the compound.

A mixed solution of [0032] is added while stirring to obtain a homogeneous solution, thereby obtaining a lotion having a skin whitening effect.

[0033]

[Example] Example 1 Lotion (oil-based) Sorbitol (70%)
3.0g glycerin
5.0g Phlorin (phloroglucinol-0.
2g β-glucoside) water
Mix and dissolve 70.0g of these ingredients. In this, allantoin
0.1g polyoxyethylene hydrogenated castor oil derivative 0.5g ethanol
20.0g fragrance
Add an appropriate amount of the mixed solution while stirring to obtain a homogeneous solution to obtain a lotion having a skin whitening effect.

Example 2 Lotion (drying) Ethylene glycol
2.5g propylene glycol
5.0g silicone
0.
0001g phlolin (phloroglucinol)
0.1g β-glucoside) water
Mix and dissolve 70.0g of these ingredients. In addition, urea
1.0
g Polyoxyethylene sorbitan
1.2g monolaurate ethanol
20gε-aminocaproic acid
0.1g fragrance
Appropriate amount Example 3 Facial cleansing cream glycerin
2.0g stearic acid
20.0g
myristic acid
10.0g lauric acid
5.0g
Polyoxyethylene lauryl ether 1.0
g florin (phloroglucinol)
0.5g β-glucoside) Flavoring and preservatives
Mix appropriate amounts of these ingredients, heat and dissolve at about 75°C, and add potassium hydroxide heated to about 75°C.
5.5g water
56
．． After adding 0 g of the solution with stirring, it is cooled to obtain a facial cleansing cream with skin whitening effect.

Example 4 Packed polyvinyl alcohol
15.0g preservative
0.1g water

75.0g phlolin (phloroglucinol - 0.3g β-glucoside) Mix these ingredients, heat and dissolve at about 80°C, cool to room temperature, and prepare glycerin.
4.0g ethanol
5.0
g fragrance
Mix appropriate amounts and dissolve uniformly to obtain a pack.

Example 5 Oil-based cream beeswax
10.0g paraffin wax
6.0g lanolin
3.0g isopropyl myristate
6.0g squalane

8.0g liquid paraffin
25.0g Florin (phloroglucinol - 0.5g β-glucoside) Polyoxyethylene sorbitan
1.8g Monostearate Sorbitan Monostearate
4.2g preservative
Mix appropriate amounts of these ingredients, heat and melt at about 75°C, and add propylene glycol heated to about 75°C.
2.0g Borax Sand
0.7g urine
Basic
5.0g water

Add 28.0 g of the mixture with stirring, and after cooling, add an appropriate amount of fragrance at 55°C, cool to 45°C while stirring, and leave to obtain an oily cream.

Example 6 Florin (phloroglucinol-β-
Glucoside) 0.5g was dissolved and a peeled apple was brought into contact with the solution for 2 minutes. The control group (no contact) changed color after 5 minutes, but the apples that were brought into contact with the agent for preventing browning of fruits and vegetables consisting of the tyrosinase inhibitor of the present invention changed color after 5 minutes.
No discoloration was observed even after 5 minutes.

Example 7 Seafood browning inhibitor L-ascorbic acid
3.0g lactose
65.0g
Phlolin (phloroglucinol-0)
．． 5g β-glucoside) Sorbitol
6.0gL-sodium ascorbate 20.0g alum

Dissolve 5.5 g of the mixture in 500-1000 ml of water or seawater and soak the seafood for 5-10 minutes to suppress browning of the seafood.

[Brief explanation of the drawing]

FIG. 1 is a graph showing the tyrosinase inhibitory effect of the tyrosinase inhibitor of the present invention.

Claims (4)

[Claims] Claim 1: The following general formula I [Formula 1] [wherein R1 individually represents a hydrogen atom or a glucose residue, R2 represents a hydrogen atom or a group [Formula 2], provided that at least one of R1 is A tyrosinase inhibitor containing as an active ingredient a compound which always represents a hydrogen atom, but all of R1 and R2 do not represent hydrogen at the same time. 2. The tyrosinase inhibitor according to claim 1, which contains a compound of the formula [Image Omitted] as an active ingredient. 3. The tyrosinase inhibitor according to claim 1, which contains a compound of the formula [Image Omitted] as an active ingredient. 4. The tyrosinase inhibitor according to claim 1, which comprises a compound of the formula [Image Omitted] as an active ingredient.