JP2664699B2 - External preparation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a hydrophilic external preparation having enhanced percutaneous absorption promotion properties, and more specifically, kojic acid, placental extract, vitamin C, The present invention relates to a hydrophilic external preparation containing a saponin extracted and purified from a specific plant as a percutaneous absorption enhancer in a hydrophilic external preparation containing a melanin production-inhibiting active ingredient composed of hydroquinone or a derivative thereof.

[Conventional technology and problems] All external preparations such as pharmaceuticals, quasi-drugs, and cosmetics
An effective ingredient having a pharmacological activity is effective only when it penetrates the skin and is absorbed into a body tissue, and its effect largely depends on the skin permeability of the active ingredient. However, the skin tissue has an action of excreting mainly from the body, and is resistant to absorption from outside the body. Therefore, how to efficiently absorb the active ingredient through the skin is a major issue for external preparations.

To address such issues, various studies have been conducted to enhance the transdermal absorption of the active ingredient. One of them is the development of a transdermal absorption enhancer that assists and promotes the transdermal absorption of the active ingredient. is there.

Currently known dermal absorption enhancers include dimethyl sulfoxide (DMSO), urea, alcohols, oleic acid, pyrrolidone derivatives, and Azone (Azone). There is a problem in safety such as not being played or skin irritation, and it is not yet sufficient. Further, these percutaneous absorption enhancers can only be found empirically by numerous screenings, and their development requires a great deal of effort.

[Means for Solving the Problems] The present invention relates to a transdermal absorbability of a melanin production-inhibiting active ingredient in which saponin extracted and purified from a specific plant is composed of kojic acid, placental extract, vitamin C, arbutin or a derivative thereof. Based on the surprising finding that it significantly promotes

That is, according to the present invention, kojic acid, placenta extract, vitamin C, hydroquinone or a derivative thereof, one or more melanin production-inhibiting active ingredients selected from the group consisting of medicinal carrot, loofah, soybean, The present invention provides a hydrophilic external preparation containing saponin obtained by purifying a water or water-ethanol extract of a plant selected from the group consisting of Kiraya, liquorice and fennel.

[Action] Saponin used as a transdermal absorption enhancer in the present invention is obtained by purifying a water or ethanol extract of a plant selected from the group consisting of medicinal carrot, loofah, soybean, quilla, liquorice and fennel. In particular, a purified water or water-ethanol extract of medicinal carrot is preferably used. These extracts have been used in Chinese medicine since ancient times as nutrient tonics, anti-inflammatory agents, blood circulation promoters, granulation formation inhibitors, cell activators, fatigue, inotropic / strong semen and analgesics.

In addition, the melanin production-inhibiting active ingredient used in the present invention is kojic acid, placenta extract, vitamin C, hydroquinone or a derivative thereof, and in Examples described later, it is a typical melanin production-inhibiting active ingredient. It discloses the transdermal absorption properties of arbutin, which is known as a derivative of kojic acid and hydroquinone.

The dosage form of the external preparation of the present invention is not particularly limited. Examples of the dosage form include cosmetics such as lotion, emulsion, cream, pack, emulsion, liniment, ointment, cataplasm, lotion, hair growth, Examples include various external preparations such as a medicament such as a hair restorer and a quasi-drug. The blending ratio of the transdermal absorption enhancer of the present invention varies depending on the type and amount of the melanin production-inhibiting active ingredient, the dosage form, the pH, the method of use, etc., but is usually 0.01 to 10 g, preferably 0.1 to 1 g of the active ingredient. ~ 3.
It is 0g. The external preparation itself is usually formulated.

Saponin is safe for the skin and there is no problem in blending it with the hydrophilic external preparation of the present invention.

EXAMPLES Next, the hydrophilic external preparation of the present invention will be described with reference to Production Examples, Test Examples, and Formulation Examples, but the present invention is not limited thereto.

Production Example [Carrot saponin] 10 kg of carrot (pharmacopoeia) was finely chopped, 30% by volume of ethanol 30 was added thereto, left at room temperature for 2 days, and then clothed. To the residue, 30% by volume of ethanol 30 was added, and the same operation was performed. This was repeated three times in total, and the combined solutions were concentrated and concentrated under reduced pressure to obtain about 4 kg of a brown extract.

After water-saturated n-butanol 12 was added and dissolved therein, water 10 was further added, and the mixture was shaken well. After standing, the n-butanol layer was separated. n-Butanol was distilled off under reduced pressure,
About 300 g of crude saponin (crude saponin content 85.0-95.0
%).

In addition, saponin could be similarly extracted from loofah (whole plant), soybean (germ), quilla (bark), liquorice (root), kikyo (whole plant) and the like.

Test Example 1 The concentration of carrot saponin (manufactured by Tokiwa Kampo Pharmaceutical Co., Ltd.) in a 1% aqueous solution of kojic acid (containing 5% ethanol) was 0.02.
%, 0.2% and 1.0% to prepare samples, and the following in vitro permeation test was performed. The results are shown in Table 1.

(Test method) The back skin collected from a male hairless mouse of 7 to 8 weeks of age (weight about 30 g) was set in a Franz cell (FDC-400 manufactured by Crown Glass), and the sample (100 ml) was placed on the donor side. Put, pH 7.4 phosphate buffer and a mixture of physiological saline in equal amounts, kanamycin sulfate as a preservative 20μg / ml
The added solution is used as a receptor solution, and the amount of kojic acid permeating into the receptor solution is quantified over time by the HPLC method. Test three times for each concentration. The average value was used as data.

As is clear from Table 1, the permeation amount of kojic acid increases as the concentration of saponin increases. A promoting effect was already observed at a saponin concentration of 0.02% (sample 3),
At 2% (sample 2), after about 24 hours, about 60% of kojic acid
% Transmitted. At 1.0% (sample 1), the permeation amount was about 13 times that of the control (sample 4) after 10 hours. The lag time of kojic acid permeation through the skin was 8 hours in the control (sample 4), 4 hours in 0.2% (sample 2) and 3 hours in 1.0% (sample 1).
It can also be seen that the immediate effect is improved.

Test Example 2 In addition to using a sample prepared by adding carrot saponin (manufactured by Tokiwa Kampo Pharmaceutical Co., Ltd.) to a 1% aqueous solution of arbutin, which is a derivative of hydroquinone, so that the concentrations would be 0.1%, 1.0%, and 3.0%. In the same manner as in Test Example 1, the effect of promoting percutaneous absorption was examined.

 The results are shown in Table 2.

Formulation Example 1 (Ointment) A Sorbitan monostearate 1.5% Self-emulsifying glyceryl monostearate 3.5% Cetanol 2.0% Salami beeswax 3.0% Lanolin 5.0% Liquid paraffin 30.0% Preservatives proper amount B Propylene glycol 5.0% Purified water -100% C Placental extract 3.0% D Kirayasaponin 0.5% (Preparation method) Heat and dissolve the components belonging to A (oil phase). Separately, the components belonging to B are dissolved by heating (aqueous phase). The aqueous phase is added to the oil phase, and the mixture is emulsified with stirring and then cooled. On the way, C and D were added to obtain an ointment.

Formulation Example 2 (Cream) A Sorbitan monostearate 2.0% Lipophilic glyceryl monostearate 3.0% Stearic acid 5.0% Behenyl alcohol 5.0% Squalane 5.0% Jojoba oil 1.0% Liquid paraffin 12.0% B 1,3 butylene glycol 5.0% Purified water -100% C Kojic acid 1.0% Carrot saponin 0.2% Purified water 8.0% (Production method) Heat and dissolve components belonging to A (oil phase). The components belonging to B are dissolved by heating (aqueous phase). The aqueous phase is added to the oil phase and emulsified. After cooling with stirring, C was added to obtain a cream.

Formulation Example 3 (pack) (cream pack) A POE (20) behenyl ether 1.0% POE (40) sorbitol tetraoleate 2.0% lipophilic glyceryl monostearate 2.0% behenyl alcohol 3.0% squalane 25.0% glycerin octoate 10.0 % Preservatives Appropriate amount B 1.3-butylene glycol 5.0% Purified water -100% C Ascorbic acid 1.0% Hetimasaponin 1.0% Purified water 8.0% (Production method) Heat and dissolve components belonging to A (oil phase). Separately, the components belonging to B are dissolved by heating (aqueous phase). After the aqueous phase was added to the oil phase and stirred and emulsified, C was added during cooling to obtain a creamy pack.

Formulation Example 4 (emulsion) A POE (20) sorbitan monostearate 2.0% Lipophilic glyceryl monostearate 1.5% Stearic acid 5.0% Squalane 15.0% Avocado oil 3.0% Liquid paraffin 5.0% B 1,3-butylene glycol 5.0% Glycerin 5.0% Purified water -100% C Arbutin 1.0% Licorice saponin 0.5% Ethanol 5.0% (Production method) Heat and dissolve components belonging to A (oil phase). The components belonging to B are dissolved by heating (aqueous phase). Add oil phase and emulsify.
After cooling with stirring, C was added to obtain an emulsion.

[Effects of the Invention] The hydrophilic external preparation of the present invention greatly enhances the percutaneous absorption of a pharmacologically active ingredient, increases the pharmacological action of a melanin production-inhibiting active ingredient, and further improves the immediate effect.

Claims (1)

(57) [Claims] (1) one or more melanin production-inhibiting active ingredients selected from the group consisting of kojic acid, placental extract, vitamin C, hydroquinone or a derivative thereof;
A hydrophilic external preparation containing saponin obtained by purifying a water or water-ethanol extract of a plant selected from the group consisting of medicinal carrot, loofah, soybean, quilla, liquorice and fennel.