JPS638313A - Drug capable of inhibiting melanization for external use - Google Patents

Abstract

PURPOSE:The titled drug, containing an aqueous liver extract of a mammal or bird and used for external therapy of pigmentation, e.g. chloasma, etc. CONSTITUTION:The titled drug for external use containing an aqueous liver extract of a mammal or bird in an amount of 0.01-10wt% based on the total weight. The drug for external use, together with a base, adjuvant, etc., is formulated into the form of an emulsion, lotion, ointment, etc., and effect is produced normally by applying to affected parts 3 times a day after washing the face.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a melanin production inhibiting topical drug used for topical treatment of pigmentation disorders such as melasma.

[Conventional technology]

Continuous oral administration of vitamin C is used as a treatment for pigmentation disorders such as melasma, but once the degree of pigmentation has reached a moderate level, continuous oral administration of vitamin C often does not improve the condition. In addition, as a topical treatment, hyperpigmentation is thought to be caused by an increase in the amount of melanocytes in the epidermal cells caused by the enhancement of melanocyte function, and as a way to suppress this excessive production of melanin, the effect of ultraviolet rays, which enhances melanocyte function, is used. To prevent this, methods have been used to use substances that scatter light such as powders such as talc, zinc white, and titanium oxide, or ointments containing ultraviolet absorbers such as paraaminobenzoic acid.

It is also known to be used as an external preparation containing a depigmenting agent such as a substance that suppresses melanin production in the epidermis, hydroquinone, or a hydroquinone derivative.

[Problem that the invention seeks to solve]

In the prior art, light blocking agents used in external drugs for topical treatment of pigmentation disorders are used to prevent pigmentation from increasing due to sunlight;
It is used in conjunction with other therapies, and if used alone, it cannot be expected to be effective as a topical drug for pigmentation disorders.

External preparations of hydroquinone and hydroquinone derivatives (hydroquinone monoverzyl ether, etc.) used as depigmenting agents may cause patchy or reticular vitiligo as a side effect, and are not preferred as external treatments for pigmentation disorders and the like. An object of the present invention is to provide an external drug that sufficiently suppresses melanin production for use in external therapy for pigmentation disorders and the like.

[Means for Solving the Problems] In order to achieve the above object, the present inventors conducted intensive research and found that aqueous extracts of livers of mammals and birds have a melanin pigment production suppressing effect. After confirming this, the present invention was completed by discovering that by incorporating this component into the base of a topical drug, it has a preventive and therapeutic effect on hyperpigmentation caused by melasma and the like.

The present invention is a melanin production inhibiting topical drug characterized by containing an aqueous extract of mammalian or bird liver.

The active ingredient of the present invention is a water-soluble extract from mammalian or avian liver, which can be obtained by conventional extraction methods. For example, as the liver, any of the livers of mammals such as cows, pigs, sheep, and goats, and the livers of birds such as chickens can be used. For extraction, the liver was washed with water to remove blood, and then crushed to give a crab-like shape.Add 2 to 3 times the amount of water, stir for several hours, and then perform a whitening operation.8!
An extract can be obtained through a filtration process.

Next, an example of the production of liver extract, which is the active ingredient of the present invention, will be given.

Production Example 1 After grinding 1 kg of pig liver H, adding 2e of water and performing stirring extraction for 3 hours, lactic acid was added to adjust the pH to around 4.5, and the temperature was heated to 80 ° C. or higher. The protein was denatured and filtered together with the tissue layer, and the filtrate was further filtered using diatomaceous earth to obtain extract 2.51. The obtained extract has a specific gravity of 1.003-1.008 and a pH of 4.5-5.5.
, evaporation residue 2.0 g / 100ml or less, total nitrogen 90-150 / 100ml, nitroprusside reaction,
Both diazo reactions are positive.

Production Example 2 20a of purified water is added to 10kg of chicken liver, the Mi texture is crushed using a mixer, etc., and the mixture is stirred and extracted at 80 to 90°C for 3 hours. Next, adjust the pH to 4.5 with 10% sulfuric acid to remove the protein.

The tissue pieces are removed by passing through a cloth or the like. Furthermore, the microparticles are centrifuged or filtered through Celite or the like to obtain an extract.

Next, after adjusting the pH to 2.0 and heating it to around 50℃, gradually add 20 g of cuprous oxide and stir gently for 2 to 3 minutes. Centrifuge and collect. This copper salt is washed several times with cold purified water, hydrogen sulfide gas is blown into the suspension of 5β in purified water, and the copper is precipitated as copper sulfide. Excess hydrogen sulfide can be removed by reducing the pressure of the liquid filtered through a filter paper to 1M1ii until the volume reaches about 115. This extract usually ends up with 2
It is adjusted to 01 and used in cosmetics.

The water-oil extract of the liver of a mammal or bird, which is the active ingredient of the present invention, is added to the base, auxiliary agent, etc. usually used for each topical drug in an amount of 0.01 to 10% (by weight) to the total amount of the drug. shall be.

The topical drug of the present invention is mainly a base commonly used in topical preparations such as emulsions, lotions, and ointments.

It is an external preparation such as an auxiliary agent. Each of these preparations is prepared by combining the above-mentioned active ingredients with a base, an auxiliary agent, etc. commonly used in each preparation, and a method commonly used.

Next, a test example showing the inhibition of melanin production by the melanin production-inhibiting topical drug of the present invention will be given.

(1) Tyrosinase inhibition test (test method)? 7 Killvain buffer pH 6,8 (Mcllvain
Buffer) 0.9■, sample 1 to L-tyrosine 1-
- After incubating the solution for 3 minutes, matsuyu room tyrosinase was added and further incubated to detect dopachrome produced every minute (maximum absorption wavelength 475 mm).
) was measured.

As samples, the active ingredient of the present invention obtained in Production Example (2) was 2.5W/V%, 6.25W/V%, and 12.5W.
/V%, and water was used as a control.

The above results are shown in the attached figure.

As is clear from this figure, the active ingredient of the present invention exhibited excellent tyrosinase inhibitory activity.

(2) Human skin application test (test method) An application test of the ointment of the present invention was conducted on 30 melasma patients at three hospitals, A, B, and C.

The final judgment will be made by visual observation 3 months after the start of application. Invalid: White color is not allowed.

Slightly effective: Slight whitening was observed. Effective: Whitening was clearly observed.

Effective results: Complete recovery or something close to it.

It was judged as.

From the above results, out of a total of 100 patients at the three hospitals, 8 patients had a poor response, 16 had a moderate response, 61 had a good response, and 15 had an excellent response.

A total of 92 patients with an efficacy rate of 92 from moderately effective to excellent efficacy.
%Met.

〔Example〕

Next, examples of the present invention will be described.

Example 1 (Ointment) Polyethylene glycol monostearate (40E, O
) 2.00 g, self-emulsifying glyceryl monostearate 5. OOg, stearic acid 5.00g, behenyl alcohol 1.00g, liquid paraffin 10.00
g, 10.00 g of glyceryl trioctanoate, and 0.20 g of paraoxybenzoic acid methyl ester were dissolved by heating. Add 1.3-butylene glycol and 5. A heated solution of OOg and 53.80 g of purified water is added, stirred to emulsify, and cooled. 8.0 g of the liver aqueous extract obtained in Production Example (1) is added to the emulsion thus obtained, stirred, and after cooling, the emulsion is filled into a container and used as a tested product.

Example 2 (Emulsion) Polyoxyethylene sorbitan monostearate (20
E, O,) 1.00 g, polyoxyethylene sorbisoto tetraoleate (60E, 0) 0.50 g,
'FA oil type upper type glycerin monostearate 10g, stearic acid 0.50g, behenyl alcohol 0.50
g, avocado oil 4.00 g, ) glyceryl rioctanoate 4.00 g, and paraoxybenzoic acid methyl ester 0.20 g are heated and dissolved. and 5. 1,3-butylene gelcol. OOg.

A heated solution of 0.14 g of xanthan gum, 5 g of the liver aqueous extract obtained in Example 2, and 83.16 g of purified water is added, emulsified, stirred, and cooled. A small amount of fragrance is added to this liquid, stirred and mixed, and after cooling, it is filled into a container and used as a product after inspection.

Example 3 (Lotion) Add 110 g of the liver water extract obtained in Example 1, paraoxybenzoic acid methyl ester o, to g, hyaluronic acid 0.01 g, a trace amount of fragrance, and purified water to make a total volume of 100 g.
g, stir, mix, fill into a container, and use as a product after inspection.

The melanin production inhibiting topical drug of the present invention is used as appropriate depending on the symptoms, but it is generally effective by applying it to the affected area three times a day after washing the face.

〔Effect of the invention〕

The topical drug of the present invention is extremely effective in preventing and treating pigmentation disorders caused by melasma and the like by applying it to the affected area.

[Brief explanation of drawings]

The figure shows the dopachrome production of the active ingredient of the invention. Circular - - is a liquid containing 2.5 W/V% of the active ingredient, -x- is a liquid containing 6.25 W/V% of the same, - Sonoichi is a liquid containing 12.5 W/V of the same.
% dopachrome production of the liquid. -〇- indicates dopachrome production in water, which is a control.

Claims (1)

[Scope of Claims] 1. A melanin production-inhibiting topical drug characterized by containing a mammalian or avian liver water extract. 2. Liver water extracts of mammals and birds account for 0.0% of all external medicines.
2. The melanin production inhibiting topical drug according to claim 1, wherein the melanin production suppressing agent is 0.01 to 10% (by weight).