JP2501593B2 - Topical agent for suppressing melanin production - Google Patents

Description

TECHNICAL FIELD The present invention relates to an external preparation containing liquiritin as an active ingredient and having a melanin production inhibitory effect.

[Prior Art] Conventionally, a flavone compound has a tyrosinase activity inhibitory action, and many techniques are known for making use of this action to prepare a cosmetic or a skin application agent. For example, as a quercetin as an active ingredient, JP-A-55-92305, JP-A-57-14517, as a quercetin fatty acid ester as an active ingredient, JP-B-58-34477, As those containing myricetin, fisetin, guchiscetin, rhamnetin and the like as active ingredients, there are disclosed in JP-A-55-1114.
No. 11, JP-A-57-35506, and those containing 3-hydroxychromone compounds as active ingredients
55-111410 and JP-A-55-143908.

There is also known a technique in which an extract from licorice is blended with a cosmetic to prepare a spot-preventing cosmetic and a moisturizing cosmetic. For example, as a stain-proof cosmetic, JP-A-60-214721, JP-A-61-122209, as a moisturizing cosmetic,
They are disclosed in JP-A-60-258104. However, in these licorice extracts, although liquiritin is contained as a trace component, like the present invention,
There is no example in which liquiritin is incorporated into cosmetics, recognizing that it has a melanin production suppressing effect.

[Problems to be Solved by the Invention] An object of the present invention is to provide an external preparation having a safe and effective melanin production suppressing effect, which is different from known active ingredients.

[Means for Solving the Problem] As a result of intensive studies for achieving the above-mentioned object, the present inventors have found that liquiritin has an excellent melanin production inhibitory action, and completed the present invention.

The present invention is an external preparation containing liquiritin as an active ingredient.

Liquiritin of the present invention is a compound contained in licorice and having the following structural formula.

Licorice, which is a raw material of the extract of the present invention, is a medicinal plant of the legume family, and its powder has been used as an expectorant, antiphlogistic, and antispasmodic for a long time.

Licorice extract is also listed in the Japanese Pharmacopoeia as an orally administered drug for the treatment of antitussive, expectorant, gastritis, gastrointestinal function adjustment, eczema and the like.

As liquiritin, a licorice extract (listed in the Japanese Pharmacopoeia) obtained by immersing dry powder of licorice in water, filtering, and then evaporating the filtrate extracted with ethanol can be used, but this method has a low content of liquiritin. However, it is not preferable as a method for obtaining liquiritin for use as a melanin production inhibitor.

In the present invention, the licorice dry powder is preferably immersed in water, and the extract obtained by further extracting the extract extracted with a lower alcohol such as ethanol or methanol with n-butanol is filtered to obtain an insoluble matter. It is recommended to use an extract with a high content of liquiritin, which is obtained by separating and concentrating.

The external preparation of the present invention is meant to include cosmetics such as creams, lotions, and packs, as well as quasi-drugs such as ointments, emulsions, lotions, and liniments that are used externally.

To produce the external preparation of the present invention, the active ingredient liquiritin is dissolved in a solvent such as ethanol and mixed into the external preparation base, or the licorice extract containing liquid liquiritin at a high concentration as a concentrated solution, Alternatively, it is dried by an appropriate drying means such as spray drying and mixed as a powder with a base for an external preparation to be manufactured.

The content of these active ingredients in the external preparation is about 0.06 to 6% (weight) with respect to the total amount of various external preparations.

When the external preparation of the present invention, for example, in a lotion or lotion, glycerin, a moisturizing agent such as propylene glycol, a skin nutrient, etc. are dissolved in purified water,
A preservative, a fragrance, etc. are dissolved in alcohol, and both are mixed and solubilized at room temperature. At this time, an alcohol solution of liquiritin, which is an active ingredient, is added to the aqueous phase to prepare a lotion or lotion.

In a cream or ointment, purified water has a hydrophilic component,
For example, a humectant such as glycerin or sorbit is added to form an aqueous phase portion, and an oil phase portion is a solid oil content such as beeswax, paraffin, microcrystalline wax, ceresin, higher fatty acid, hardened oil, and semisolid such as petrolatum, lanolin, and glyceride. Oil components such as squalane, liquid paraffin, and various oils such as ester oils are mixed with oil components such as preservatives and surfactants for adjustment. The aqueous phase obtained in this manner is heated, and the oil phase heated to the same temperature while gently stirring is gradually emulsified to give a cream or ointment. An alcoholic solution of liquiritin, which is an active ingredient, is added to the phase portion to prepare a cream or ointment.

In emulsions, humectants such as glycerin in purified water,
Add an acid or alkali pH adjuster, mix with heating, and add ethanol to form the aqueous phase. Beeswax, paraffin, and other solid oils, petrolatum, lanolin, and other semisolid oils, squalane, liquid paraffin, and various ester oils. To the liquid oil component, an oil component such as a preservative or a surfactant is added and mixed and heated to form an oil phase part, and the oil phase part is added to the water phase part for preliminary emulsification. A protective colloid agent such as methylcellulose is added, and the mixture is uniformly emulsified with a homomixer to give an emulsion. At this time, an alcohol solution of liquiritin, which is an active ingredient, is added to the aqueous phase to obtain an emulsion.

In packs, moisturizers such as glycerin, polyvinyl alcohol, and filming agents such as bee gum are added to purified water to swell, and if necessary, powders such as kaolin, talc, and zinc oxide are added, and fragrances and preservatives are added. Ethanol in which a drug or the like is dissolved is added and kneaded until a paste is formed. At this time, an alcohol solution of liquiritin, which is an active ingredient, is added to form a pack.

The following methods are advantageous extraction methods for obtaining an extract containing a large amount of liquiritin from licorice.

Conventional licorice extract, for example, shredded licorice or its water-immersed product is extracted by adding a lower alcohol such as ethanol,
The filtered licorice extract was extracted by further adding n-butanol, washed with water, and subjected to butanol removal to obtain an extract. This extract contains liquiritin and 4'-O-
[Β-D-Abio-D-furanosyl- (1 → 2) -β-
The main component is D-glucopyranosyl] liquiritigenin, and the content ratio is 25:18.

[Examples] Next, production examples of liquiritin, which is the active ingredient of the present invention, and Examples of the present invention will be described.

<Production Example> 50 kg of licorice is crushed, ethanol 400 is added thereto, and the mixture is subjected to reflux heat extraction for 2 hours. This operation is repeated twice, and the extract is completely concentrated at 60 ° C or lower to obtain 15 kg of a concentrate. This is dissolved in 100 water. Saturated hydrous n-butanol 100 was added to this, well stirred at room temperature for 30 minutes and allowed to stand to separate the butanol layer.

The same amount of 6-butanol was added to the residual liquid, and the same operation was performed.
Repeat times. Combine the n-butanol layers three times and mix with water 100
It is washed twice with water to remove sugar, tannin and the like.

The butanol extracts washed with water are combined and the butanol is distilled off at 60 ° C or lower. 300 water is added to the residue to dissolve by heating, and the insoluble matter is filtered off. The filtrate is further concentrated to 50 and left overnight to separate the supernatant by decantation. This supernatant is 60 ℃
Concentrate below to obtain 1 kg of licorice flavonoid fraction. The yield is 2% of the raw material.

The melanin production inhibitory action of liquiritin, which is the active ingredient of the present invention, will be clarified by the following test.

* Liquiritin Extraction Conditions Table 1 shows the concentration of liquiritin and the dry matter and dry powder weight of the extract when extracted at 25 ° C. and 80 ° C. with 5 volumes of various solvents by the following steps. The evaluation results of B16 are shown in Table 2.

[Liquiritin extraction method] * ¹ Water ethanol 50% ethanol 99% ethanol * ² 25 ℃ 80 ℃ <Test example> a) Cells used Mouse melanoma B16 cells (hereinafter referred to as B16 cells) b) Culture medium Eagle's MEM medium containing 10% fetal calf serum c) Test method 50% ethanol aqueous solution was supplemented with liquiritin. 0.1% was dissolved and this was added to the culture solution of B16 cells. After 5 days of culture,
A cell pellet was prepared and the color tone of the cells was observed.

d) Test result As a result, when liquiritin was added at 5, 10 and 20 μg / ml, respectively, whitening of cells was observed depending on the concentration of addition. Cell proliferation was slightly suppressed by 20 μg / ml of liquiritin.

[Prescription example] The prescription example of the present invention is given below.

The "appropriate amount" in the formulation examples means the amount that makes the entire formulation 100% by weight.

<Formulation Example 1> (Ointment) (%) 1. Liquiritin 2.0 2. Polyoxyethylene stearyl ether 2.0 3. Polyoxyethylene cetyl ether 2.0 4. Beeswax 6.0 5. Cetanol 6.0 6. Isopropyl palmitate 10.0 7. Liquid paraffin 30.0 8. Polyethylene glycol monostearate 1.0 9. Methyl paraoxybenzoate 0.2 10. Purified water Appropriate amount Preparation Method A.1 to 8 are mixed, heated and dissolved.

Heat B.9 to 10 to dissolve.

Add B to C.A, emulsify, stir, and cool.

After cooling D.C, focus on the container and make the product after inspection.

<Prescription example 2> (Emulsion) (%) 1. Liquiritin 1.0 2. Self-emulsifying glycerol monostearate 0.5 3. Polyoxyethylene cetyl ether 2.0 4. MC stearic acid 2.0 5. Cetanol 1.5 6. Isopropyl myristate 10.0 7 .Methyl paraoxybenzoate 0.2 8. Fragrance trace amount 9. Purified water proper amount Manufacturing method A.1 to 6 are heated and dissolved.

Heat and dissolve B.7-9.

Add B to C.A, emulsify, stir, and cool.

After cooling D.C, fill it in a container and make it a product after inspection.

[Effects of the Invention] The present invention has found that Liquiritin, which is a component of licorice conventionally used as a herbal medicine, is selectively used as a melanin production inhibitor, and the melanin production inhibitor is safe. Is high, and also exhibits an excellent melanin production inhibitory action.

Claims (1)

(57) [Claims] 1. An external preparation for suppressing melanin production, which comprises liquiritin as an active ingredient.