JPH06305932A - Skin external agent - Google Patents

Abstract

PURPOSE:To provide a skin external agent containing glycyrrhetinic acid monoglucuronide or its salt as an active ingredient, and effective for preventing skin roughness, skin inflammation, skin UV ray erythema, etc., and for mitigating skin irritation caused by irritative substances. CONSTITUTION:A skin external agent containing as an active ingredient glycyrrhetinic acid monoglucuronide obtained by enzymatically partially hydrolyzing glycyrrhizin to remove a glucuronic acid molecule in its saccharide part, or its salt. The active ingredient exhibits an almost twice potency that of the glycyrrhizin, gives solutions having excellent stability, and is weak in foamability. The skin external agent is a new safe and easily usable skin external agent. The external agent can be used for medicines, qusidrugs, various cosmetics, shampoos, rinses, packs, soaps, bath agents, hair-raising agents, etc. When the external agent is added to the cosmetic, the external agent is used in an amount of approximately 0.001-5wt.% as the glycyrretinic acid monoglucuronide.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to rough skin, skin inflammation,
The present invention relates to a skin external preparation effective for preventing erythema of ultraviolet rays and alleviating skin irritation caused by irritating substances.

[0002]

2. Description of the Related Art Glycyrrhizic acid and its salts (hereinafter referred to as glycyrrhizin) obtained from rhizomes and runners of legumes, licorice, have an anti-inflammatory action, and therefore are components for preventing rough skin, skin inflammation, ultraviolet erythema, etc. It is widely added to cosmetics such as lotions, creams and emulsions, quasi-drugs or external medicines.

However, since glycyrrhizin has a sugar chain consisting of two molecules of glucuronic acid, it has a strong hydrophilic property, and therefore, depending on the intended use, it may not be possible to obtain a sufficient use effect. Also, when added to liquid products such as lotions,
In the acidic region of pH 5.5 or less, there is a drawback that viscosity is increased and gelation occurs, and further, foaming is strong, and bubbles generated thereby do not disappear for a long time.

Glycyrrhizin, which is a genin of glycyrrhizin, is superior to glycyrrhizin in anti-inflammatory action, but it is difficult to determine the formulation because it is difficult to dissolve in a solvent used for general cosmetics and quasi drugs. There is a point. Rough skin, skin inflammation, as substances effective in preventing UV erythema, azulene, allantoin, indomethacin, various plant extracts, proteins, polysaccharides, animal extracts, etc. are known in addition to glycyrrhizin and glycyrrhetin. , Those having excellent use effects have problems in safety and stability, and those having good safety and stability do not have sufficient effects.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in view of the above-mentioned problems in the case of using glycyrrhizin and other substances as an external preparation for skin which is expected to have an anti-inflammatory effect.
It is intended to provide a new external preparation for skin which is surely effective in use, safe, and easy to use.

[0006]

The external preparation for skin of the present invention, which has succeeded in achieving the above objects, comprises monoglucuronide glycyrrhetinic acid or a salt thereof. Suitable salts of glycyrrhetinic acid monoglucuronide for the external preparation for skin of the present invention are dipotassium salt, monopotassium salt, diammonium salt, monoammonium salt, disodium salt, monoammonium salt and the like.

Glycyrrhetinic acid monoglucuronide and its salt are glycyrrhizin analog compounds obtained by partially hydrolyzing glycyrrhizin enzymatically to remove one molecule of glucuronic acid in the sugar moiety. It has about twice the potency, excellent solution stability, and weak foaming power. The anti-inflammatory effect of glycyrrhetinic acid monoglucuronide was confirmed by the following carrageenin edema test.

[Test by Carrageenin Edema Method] Weight 1
68-199g male Wistar rats (6 per group)
The right hind foot volume V ₀ of the foot volume measuring device TK-
105 (Muromachi Kikai Co., Ltd.). To the test group, 0.1 ml of one of the following sample solutions is applied to the hind foot pads, and 1 hour after that, 0.1 ml of a 1% carrageenin physiological saline solution is injected into the sample solution application site. Sample solution a: monoglucuronide dipotassium glycyrrhetinate 1.0% solution solvent ethanol: 1,3-butylene glycol: water = 7:
2: 1 sample solution b: dipotassium glycyrrhizinate 1.0% solution (for control) solvent ethanol: 1,3-butylene glycol: water = 5:
2: 3 sample solution c: indomethacin 1.0% solution (for control) solvent ethanol: 1,3-butylene glycol: water = 7:
2: 1

After injecting carrageenin, the paw volume V ₁ is measured after a lapse of a predetermined time, and the edema rate A is calculated by the following equation. A (%) = (V ₁ −V ₀ ) × 100 / V _{0 For the} control group, 0.1 ml of the solvent of the sample solution was used instead of the sample solution.
Is applied and treated with carrageenin in the same manner as in the case of the test group to cause inflammation, and the edema rate A ′ is determined. The carrageenin edema inhibitory rate was calculated from the edema rates A and A ′ using the following formula, and used as an index of the anti-inflammatory activity of the test substance. Carrageenin edema inhibition rate (%) = (A′−A) × 100
The results of the / A 'test are shown in Table 1, and the salt of glycyrrhetinic acid monoglucuronide showed an edema inhibitory rate about twice that of glycyrrhizin, and was also excellent in the duration of the effect.

[0010]

[Table 1] Carrageenin edema inhibitory rate (%) Sample 1 hour 2 hours 3 hours 4 hours later Glycyrrhetinic acid monoglucuronide / K ₂ 21.2 22.9 25.0 12.0 Dipotassium glycyrrhizinate 17.6 13.2 12.4 9.4 Indomethacin 38.9 26.3 26.8 16.8

In order to facilitate application to the skin, the external preparation for skin according to the present invention is used in combination with various medicinal and physiologically active ingredients which are usually added to drugs for dermatological diseases or quasi drugs, cosmetics, etc. Oils, waxes, higher fatty acids, and other oils; ethanol, glycerin, 1,3-butylene glycol, and other alcohols; surfactants, thickeners, antioxidants, preservatives, fragrances, coloring agents, etc. It can be applied to the skin (including the scalp) in the form of medicines, quasi drugs, various cosmetics, shampoos, rinses, packs, soaps, bath salts, hair nourishing agents and the like. When blending in cosmetics,
A preferable blending ratio is about 0.001 to 5% by weight as glycyrrhetinic acid monoglucuronide.

Examples of physiologically active ingredients which can be used in combination with the external preparation for skin of the present invention include hormones such as progesterone, corticosterone, hydrocortisone, 17β-estradiol, ethinylestradiol and estrone;
Hyaluronic acid, dermatan sulfate, keratan sulfate, chondroitin, heparin, chondroitin sulfates, chitin,
Mucopolysaccharides such as chitosan; complex lipids such as glycerophospholipids, sphingophospholipids, glyceroglycolipids, glycosphingolipids; superoxide dismutase, catalase, β-carotene, oil-soluble licorice extract, glabridin,
Ricochalcone A, baicalin, yellow jelly extract, baicalein, ginkgo extract, sowaku extract, kujin extract, hamamelis extract and other substances having active oxygen scavenging activity; allantoin, guaia azulene, kamaazulene, stearyl epsilon aminocaproic acid, Indomethacin, Zinc oxide; Arnica extract, Inchinko extract, Scutellaria extract, Oat extract, Chamomile extract, Licorice extract (water extract), Sanshishi extract, Sikon extract, Peony extract, Botanpi extract, Deer squirrel extract, birch extract, horse chestnut seed extract, quince extract, sorghum extract, rosemary extract, sawdust grass extract, mugwort extract, yokuinin extract, aloe extract, dio extract,
Botanical extracts having anti-inflammatory and anti-allergic effects such as senkyu extract, psycho extract, boifu extract, yokuinin extract, loofah extract; collagen, hydrolyzed collagen, elastin, vitronectin, fibronectin, placenta extract, royal jelly , Animal extracts such as conchiolin hydrolysates; vitamins such as retinol, retinal, retinoic acid, pantothenic acid, panthenol, riboflavin, pyridoxine, tocopherol, ascorbic acid, folic acid, nicotinic acid; nucleic acids and their bases; Amino acids; Cholesterols; Plant sterols; Lipoproteins; Bifidobacterium fermentation products, lactic acid bacteria fermentation products, yeast extracts, litchi extracts, litchi mycelium extracts, and other microorganism-derived substances;

[0013]

【Example】

Example 1 A lotion containing dipotassium glycyrrhizinate as an anti-inflammatory agent (following formulation 1) and a lotion containing the external preparation for skin (monoglucuronide dipotassium glycyrrhetinate) of the present invention (formulation 2 below), respectively. It was produced by a conventional method (numerical values are% by weight). Formulation 1 Formulation 2 Surfactant 0.5 0.5 Ethanol 4 4 1,3-butylene glycol 3 3 Paraoxybenzoic acid ester 0.12 0.12 Urea 22 Dipotassium glycyrrhizinate 0.2-Glycyrrhetinic acid monoglucuronide・ K ₂ -0.2 Purified water Remaining amount Remaining amount (surfactant: polyoxysorbitan monolaurate, 20EO)

50 ml of the lotion was placed in a 100 ml graduated cylinder equipped with a stopper, shaken 100 times, and allowed to stand still. Immediately after that, and after 5 minutes and 10 minutes, the height of foam was measured. The results are as follows. It was found that the lotion of the formulation 2 to which glycyrrhetinic acid monoglucuronide was added was less likely to foam than the lotion to which glycyrrhizin was added, and the generated foam disappeared remarkably quickly.

Example 2 A cream having the following formulation to which the external preparation for skin (monoglucuronide diammonium glycyrrhetinate salt) according to the present invention was added was produced by a conventional method (numerical values are% by weight). Surfactant A 3.5 Surfactant B 1.5 Liquid paraffin 25.0 Whale wax 5.0 Lanolin 5.0 Cetanol 2.0 Paraoxybenzoic acid ester 0.2 Glycerin 3.0 Carboxyvinyl polymer (1% aqueous solution) ) 5.0 Glycyrrhetinic acid monoglucuronide ・ (NH ₄ ) ₂ 0.2 Purified water Residual amount (Note) Surfactant A: Self-emulsifying glyceryl monostearate Surfactant B: Sorbitan monostearate

A comparative example having the same composition was prepared except that glycyrrhetinic acid monoglucuronide diammonium salt was not added. Woman with rough skin (28-45 years old) 11
A test was conducted in which the above-mentioned cream was applied to one half of the affected area and the comparative example was applied to the other half of the affected area twice a day for two months in succession. Two months later, when the skin condition was compared, it was confirmed that the area where the glycyrrhetinic acid monoglucuronide salt-added cream was applied recovered to normal skin in all 11 subjects, but the area where the comparative example was applied was confirmed. In one case, only one of them recovered to normal skin, and in the other ten cases, some improvement was observed.

Example 3 A tonic having the following formulation was prepared by adding the external preparation for skin of the present invention (monoglucuronide dipotassium glycyrrhetinate). Ethanol 60 1.3-Butylene glycol 1 l-Menthol 0.1 Salicylic acid 0.1 dl-Sodium pyrrolidonecarboxylate 0.5 Assemblage extract liquid 0.3 Hinokitiol 0.02 Glycyrrhetinic acid monoglucuronide K ₂ 0.05 Perfume 0 .2 Purified water remaining

A comparative example having the same composition was prepared, except that glycyrrhizin dipotassium was added instead of glycyrrhetinic acid monoglucuronide dipotassium salt. The tonic to which glycyrrhetinic acid monoglucuronide salt was added was clear and remained clear even after being stored at two temperature conditions of 40 ° C. and 2 ° C. for 3 months. On the other hand, the comparative example was in a slightly cloudy state immediately after production, and the one stored at 2 ° C. formed a precipitate after 3 days. When the precipitate was analyzed by high performance liquid chromatography, it was identified as glycyrrhizic acid, and it was found that the added glycyrrhizic acid deteriorated the solution properties and stability.

[0019]

Industrial Applicability As described above, the external preparation for skin of the present invention comprising monoglucuronide glycyrrhetinic acid or a salt thereof is more effective in use than glycyrrhizin, has no foaming property, and is stable in solution. Is also excellent.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location A61K 31/70 ADA

Claims (1)

[Claims] 1. An external preparation for skin comprising glycyrrhetinic acid monoglucuronide or a salt thereof.