JPH0138774B2 - - Google Patents

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]

As a treatment for pigmentation disorders such as melasma, methods such as continuous oral administration of vitamin C are used, but when the degree of pigmentation becomes severe, it is often not improved by continuous oral administration of vitamin C. In addition, hyperpigmentation is thought to be caused by an increase in the amount of melanosomes in epidermal cells caused by enhanced melanocyte function, and methods to suppress the excessive production of melanin include methods to prevent the effects of ultraviolet rays, which enhance melanocyte function, such as Methods used include substances that scatter light such as powders such as talc, zinc white, and titanium oxide, or ointments containing ultraviolet absorbers such as para-aminobenzoic acid.

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

Furthermore, cosmetics containing placenta extracts have also been disclosed (Japanese Patent Publication No. 15399/1983).

[Problem that the invention seeks to solve]

In the prior art, the light blocking line used in the topical drug in topical therapy for pigmentation disorders is used because pigmentation increases due to sunlight, so it is used in conjunction with other treatments, and this drug alone is used. Depending on its use, it cannot be expected to be effective as a topical drug for hyperpigmentation.

External preparations of hydroquinone and hydroquinone derivatives (hydroquinone monobenzyl 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. In addition, topical preparations containing melanin production inhibitors such as kojic acid and kojic acid derivatives are tyrosinase activity inhibitors, so they have a melanin production inhibiting effect without the side effects such as vitiligo seen with hydroquinone, etc. Although it is excellent as an external preparation for treating deposits, etc., it is still not sufficient.

[Means for solving problems]

The present invention is a melanin production-suppressing topical drug that contains a placenta extract and a liver extract and has a remarkable effect on skin diseases such as hyperpigmentation.

The placenta extract used in the present invention is obtained by washing the placenta of a human or an animal such as a cow, removing blood, crushing it, freezing it, etc., extracting the aqueous part with water, and then removing impurities by filtration or dialysis. It is an aqueous solution.

These placenta extracts are generally commercially available as placenta extracts and are mainly used as raw materials for cosmetics, and may be derived from humans or animals such as cows, but human-derived Placental extracts are preferred.

The animal liver extract used in the present invention is obtained by crushing and extracting the liver of an animal such as cow, pig, sheep, etc.
After washing the liver of a mammal such as a goat or a bird such as a chicken with water and removing blood, it is ground into a porridge-like form, and after adding 2 to 3 times the amount of an extraction solvent such as water and stirring for several hours, the liver is removed. Protein manipulation is performed and an extract is obtained through a filtration process. In this case, water is suitable as the extraction solvent.

Next, an example of producing a liver extract used in the present invention will be given.

Production example 1 Grind 1 kg of pig liver, add water from Step 2, stir and extract for 3 hours, then add lactic acid to adjust the pH to around 4.5, heat the temperature to 80℃ or higher, and extract the protein. It was denatured and filtered together with the tissue layer, and the filtrate was further filtered using diatomaceous earth to obtain extract 2.5.
The obtained extract has a specific gravity of 1.003 to 1.008, a pH of 4.5 to 5.5,
Evaporation residue 2.0g/100ml or less, total nitrogen 90-150
mg/100ml, nitroprusside reaction, and diazo reaction are both positive.

Production Example 2 Add 20 kg of purified water to 10 kg of chicken liver, crush the tissue with a mixer, etc., and stir and extract at 80 to 90°C for 3 hours.
Next, adjust the pH to 4.5 with 10% sulfuric acid, and remove protein tissue pieces by filtration with a cloth. Furthermore, the microparticles are centrifuged or filtered through Celite or the like to obtain an extract.

Next, adjust the pH to 2.0 and warm it to around 50℃, then gradually add 20g of cuprous oxide and stir gently for 2 to 3 hours. Copper salts such as amino acids will precipitate, so centrifuge it. Separate and collect. This copper salt is washed several times with cold purified water, and hydrogen sulfide gas is blown into the suspension in the purified water in step 5 to precipitate copper as copper sulfide. The volume of the liquid filtered through filter paper is 1/5
Excess hydrogen sulfide can be removed by concentrating under reduced pressure until the This extract is usually adjusted to a final concentration of 20% and used for external medicine.

The proportion of placenta extract and liver extract mentioned above is 10 parts placenta extract (by weight) to 5 parts liver extract.
0.01 (weight) is suitable. The proportion of these active ingredients in topical drugs is 0.1 to 10% (by weight) for placenta extract and 0.1 to 10% (by weight) for liver extract.
0.01 to 5% (by weight) can sufficiently exhibit the effect.

The external medicine of the present invention is mainly an emulsion, a lotion, an ointment, and the like. Each of these preparations contains the above-mentioned active ingredients as a base commonly used in each preparation,
It is formulated using auxiliary agents and other commonly used methods.

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

(1) Tyrosinase inhibition test (test method) 1 ml of L-doper solution (10mM) in a test tube,
Add 0.9 ml of Matsukulbane buffer (PH6.8) and 1 ml of sample, incubate for 10 minutes in a thermostatic water bath at 37°C, then add 0.1 ml of tyrosinase solution (11.000 G supernatant of B16 mouse melanoma) and stir well. Immediately set it on the spectrophotometer,
Absorbance at 475 nm was measured over time.

The samples were a placenta extract, a liver extract, a solution containing the placenta extract and 1/2 weight of the liver extract, and water as a control. The inhibition rate is the percentage of inhibition of dopachrome production after 8 minutes, with the control being 100.

The above measurement results are shown in the attached drawings. As is clear from the drawings, the combination of liver extract and placenta extract inhibits tyrosinase activity more synergistically than either alone.

In addition, liver extract, which is an active ingredient of the present invention,
It is known that placental extracts have the effect of inhibiting melanin production even when used alone, but the inventor's research revealed the mechanism of melanin production inhibition in the cell line using B16 cells used in this test. As a result of the analysis, liver extract suppresses tyrosinase activity and inhibits melanin production by chelation with copper ions that affect the activity of tyrosinase, which is involved in the early stage of melanin production, whereas placental extract suppresses the production of copper ions. No chelation was observed, demonstrating that the melanin production suppression mechanism of the placenta extract is different from that of the liver extract. As a result, a synergistic effect of the liver extract and placenta extract can be obtained due to their different melanin production inhibiting effects.

(2) Human skin application test (test method) At three hospitals, A, B, and C, stains,
An application test of the ointment of the present invention was conducted on 60 sunburn patients.

The final judgment was made by visual observation 3 months after the start of application: Ineffective: No whitening was observed.

Slightly effective: Slight whitening is observed.

Effective: Whitening is clearly observed.

Efficacy: Complete recovery or something close to it.

It was judged as.

Based on the above results, 5 out of 60 people were found to be ineffective, and 15 were somewhat effective.
There were 31 patients with effective results and 9 patients with excellent results. The efficacy rate was 91.66% in 55 patients, ranging from moderately effective to excellent efficacy.

〔Example〕

Next, examples of the present invention will be described.

Example 1 (Ointment) 2.00 g of polyethylene glycol monostearate (40E.O.), 5.00 g of self-emulsifying glyceryl monostearate, 5.00 g of stearic acid, 1.00 g of behenyl alcohol, 10.00 g of liquid paraffin,
10.00 g of glyceryl trioctanoate and 0.20 g of paraoxybenzoic acid methyl ester are dissolved by heating.
A heated solution of 5.00 g of 1,3-butylene glycol and 53.80 g of purified water was added to this and stirred to emulsify.
Cooling. 3.0 g of the liver extract and 5.0 g of the human placenta extract from Production Example 1 are added to the emulsion thus obtained, mixed and stirred, and after cooling, the product is filled into a container and used as a tested product.

Example 2 (Emulsion) 1.00 g of polyoxyethylene sorbitan monostearate (20E.O.), 0.50 g of polyoxyethylene sorbitan tetraoleate (60E.O.), 1.00 g of lipophilic glyceryl monostearate, stearic acid 0.50 g, behenyl alcohol 0.50 g, avocado oil 4.00 g, glyceryl trioctanoate 4.00 g, and paraoxybenzoic acid methyl ester 0.20 g are dissolved by heating. And 1,3-butylene glycol 5.00
A heated solution of 0.14 g of xanthan gum, 1.0 g of the liver extract of Production Example 2, 7.0 g of the human placenta extract, and 75.16 g of purified water is emulsified, stirred, and cooled. Add a small amount of fragrance to this liquid and stir to mix. After cooling the liquid obtained in this way, it is filled into a container and used as a product after inspection.

Example 3 (Lotion) 0.5g of liver extract from Production Example 2 and 5.0g of human placenta extract
g and paraoxybenzoic acid methyl ester 0.10 g,
Add 0.01g of hyaluronic acid, a small amount of fragrance, and purified water to make a total of 100g, stir and mix, fill in 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〕

When applied to the affected area, the melanin production inhibiting topical drug of the present invention is extremely effective in preventing and treating pigmentation disorders caused by melasma due to the synergistic action of placenta extract and liver extract.

[Brief explanation of drawings]

The figure shows the dopachrome production of the active ingredient of the invention.

Claims (1)

[Scope of Claims] 1. An external drug for suppressing melanin production, characterized by containing a placenta extract and a liver extract. 2. The melanin production inhibiting topical drug according to claim 1, wherein the placenta extract is a human placenta extract. 3. The melanin production inhibiting topical drug according to claim 1, wherein the liver extract is an aqueous liver extract of a mammal or bird.