JP2000191498A - Collagen production facilitative agent and preparation for external use for skin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To find out a substance effective for really rejuvenating aged skins by facilitating the synthesis of collagen in dermal fibroblasts to obtain a collagen production facilitative agent useful as a constituent for skin lotion, e.g. cosmetics or the like. SOLUTION: This collagen production facilitative agent is obtained by extracting leaves of licorice with a solvent selected from the group consisting of water, methanol, ethanol, propanol, 1,3-butylene glycol, glycerin, propylene glycol or these mixtures and the collagen production facilitative effect of the resultant extract is utilized.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a collagen production promoter which has the effect of activating collagen production by human skin fibroblasts and which is useful for preventing skin roughness, wrinkles, decreased elasticity and the like. And an external preparation for skin having a function of preventing skin aging by blending the same.

[0002]

2. Description of the Related Art In recent years, studies on skin aging have progressed, and it has been confirmed that the effects of ultraviolet rays, drying, oxidation and the like are complicatedly involved in skin aging, in addition to attenuation of metabolism due to aging. Have been.

In the action of external factors such as ultraviolet rays, the action on collagen and elastin in the dermis layer accelerates skin aging most. In other words, in the dermis layer, fibrous collagen and coiled hard protein / elastin which are entangled with it maintain the skin firmness and elasticity, but this tension retention mechanism prevents ultraviolet rays and the like. When destroyed by action, the skin becomes wrinkled, sagged and aged. Collagen can also retain moisture in its molecules, which helps keep the skin moist, so when external factors destroy collagen, the skin dries and becomes rough State.

As a means for preventing aging of the skin by the above mechanism, a method of applying a physiologically active substance such as epidermal growth factor (EGF), placenta extract, α-hydroxy acid, retinoic acid to the skin is known. It is known that EGF and placenta extract may be sensitizing due to animal-derived protein, β-hydroxy acid is strongly acidic and has skin irritation properties, and retinoic acid is stable and safe. There was difficulty in sex.

[0005] Regarding the decrease in the moisturizing property of the skin due to degradation of collagen, etc., application of sugars, amino acids, organic acids, pyrrolidone carboxylate, etc. which are natural moisturizing factors (NMF), or moisturizing agents such as mucopolysaccharides, glycerin, etc. Suppression of water evaporation from the skin by application, application of oils and fats, and other hydrophobic compounds has a certain effect. However, these means effective only for moisturizing only improve the keratin condition of the epidermis, and cannot be expected to improve the tension holding mechanism in the dermis. Also, both humectants and fats and oils generally have a poor feeling of use, and may even cause skin disorders.

[0006]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to find a substance which is effective in promoting collagen synthesis in dermal fibroblasts to truly rejuvenate aging skin, and to use such a substance for external application such as cosmetics. An object of the present invention is to provide a collagen production promoter useful as a component of an agent.

Another object of the present invention is to provide an external preparation for skin having an effect of promoting collagen production in the dermis layer and rejuvenating aging skin.

[0008]

Means for Solving the Problems A collagen production promoter which has been successfully provided by the present invention comprises, as an active ingredient, a substance which is extracted from licorice leaves and has an action of promoting collagen production by fibroblasts. Things.

The present invention also provides an external preparation for skin having the effect of preventing skin aging by blending the collagen production promoter according to the present invention.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION Licorice is a useful plant that has been used as a medicinal or sweetener material since ancient times, in which case only the root part is used. Glycyrrhizin and other useful ingredients are not in the aerial part of licorice,
Therefore, the leaves and stems have not been used at all.

On the other hand, the collagen production-promoting substance identified for the first time by the present inventors is contained only in the leaves of licorice, but not in the root extract.

Since the collagen production promoting substance is contained in the leaves of most licorice even though the content is different, the species of licorice used as a raw material of the collagen production promoter of the present invention is not limited. Glycyrrhizaglabra L., Glycyrrhiza ur commonly used for collecting root extract
The leaves of alensis Fisher, Glycyrrhiza inflata L. and the like are easily available, and the use of these leaves is also effective for resource utilization, and is therefore suitable as a raw material.

As for the licorice leaves to be used as an extraction raw material, dried preserved leaves are preferable immediately after being collected because their quality is more stable, but fresh fresh leaves may be used.

Although it has not been confirmed yet which compound in the licorice leaf extract has a collagen production promoting effect, the active ingredient can be extracted from the licorice leaf using water or a lower aliphatic alcohol. It is not extracted with hydrophobic organic solvents. Specific examples of preferred alcohols as the extraction solvent include methanol, ethanol, propanol, 1,
3-butylene glycol, glycerin, propylene glycol and the like. Mixtures of these alcohols and water are particularly preferred.

The extraction can be carried out at room temperature or under reflux with any apparatus. Briefly, the pulverized extraction raw material is put into a treatment tank filled with an extraction solvent, and the soluble component is eluted with occasional stirring. Thereafter, the residue is filtered to remove the extraction residue to obtain an extract. The resulting extract is pale in color and does not have an undesired odor, and therefore can be used as it is as the collagen production promoter of the present invention. However, usually, the concentrate or its dried product, or those obtained by subjecting them to simple purification treatments Before using. If necessary, a carrier such as dextrin and cyclodextrin, a preservative, and any other auxiliaries are added to facilitate storage and handling to prepare a powder, granule, tablet, or any other formulation. be able to.

The collagen production promoter of the present invention is absorbed percutaneously to reach fibroblasts, activate collagen production, and replenish the dermis layer with sufficient collagen. The easiest way to utilize the above action is to mix this collagen production promoter with cosmetics or any other external preparation for skin. Suitable external preparations for the skin include ointments, creams, emulsions, lotions, packs, bath preparations and the like. The preferred compounding ratio is about 0.01 to 10% by weight in terms of a standard licorice leaf extract.

The external preparation for skin containing the collagen production promoter according to the present invention contains various main agents and auxiliaries usually used in the production of the external skin preparation as long as they do not hinder the promotion of collagen production. be able to. In addition, any auxiliaries effective for enhancing the efficacy of the licorice leaf extract can be contained.

Examples of those which can be used as a skin external preparation component together with the collagen production promoter of the present invention include avocado oil, palm oil, peanut oil, tallow, rice bran oil, rice germ oil, jojoba oil, carnauba wax, lanolin, Oily components such as liquid paraffin, squalane, oxystearic acid, isostearyl alcohol; glycerin, 1,3-butylene glycol, sorbitol, polyethylene glycol, collagen, hyaluronic acid and its salts, chondroitic acid and its salts, chitin, chitosan, etc. Moisturizer;
UV absorbers such as amyl paradimethylaminobenzoate, urocanic acid and ethyl diisopropylcinnamate; antioxidants such as sodium erythorbate and parahydroxyanisole; sodium stearyl sulfate, diethanolamine cetyl sulfate, cetyltrimethylammonium chloride, polyethylene isostearate Surfactants such as glycol and glyceryl stearate; ethyl paraben,
Preservatives such as butyl paraben; complex lipids such as glycerophospholipid, sphingolipid, glyceroglycolipid, glycosphingolipid; superoxide dismutase, catalase, β-carotene, oil-soluble licorice root extract, glabridine, lycochalcone A, baicalin, Baicalein, Ginkgo biloba extract, Kudmin extract, Hamamelis extract, Huang mulberry extract and other substances having an active oxygen-scavenging action; allantoin, guaia azulene, camazulene, bisabolol, glycyrrhizic acid and its salts, glycyrrhetinic acid and its derivatives , Stearylepsiloniminocaproic acid, indomethacin, zinc oxide, anti-inflammatory substances such as hinokitiol; retinol, retinal, retinoic acid, pantothenic acid, panthenol, riboflavin, pyridoxine, Tocopherol, ascorbic acid,
Vitamins such as folic acid and nicotinic acid and derivatives thereof; γ
-A blood circulation promoting agent such as oryzanol, dextran sodium sulfate, etc .; an antiseborrheic agent such as sulfur or thianthol; an arnica extract, a cinnamon extract, a gougon extract, a oak extract, a spinach extract, a chamomile extract, a liquorice root water extract Stuff, Sanshishi extract, radish extract, peonies extract, pomegranate extract, pteronymus extract, birch extract, western horse chestnut seed extract, calendula extract, pomegranate extract, sapling extract, linden extract, rose Marie extract, Sawtooth grass extract,
Mugwort extract, rock cabbage extract, yokuinin extract, aloe extract, loquat extract, peach extract, senkyu extract, sage extract, touki extract, loofah extract, sycamore extract, panax ginseng extract, Capsicum extract, bean tea extract, tea extract, hypericum extract, malonie extract, prune extract, collagen, hydrolyzed conchiolin, elastin, vitronectin, fibronectin, placenta extract, royal jelly, bifidobacterium culture, lactic acid bacteria culture , Yeast extract,
Ganoderma mycelium extract, bougainvillea extract, brown algae extract,
Plant extracts, animal extracts, microorganism-derived components or algal extracts, such as red algae extracts and green algae extracts, which are expected to show some favorable effects on the skin; amino acids; cholesterols; Lipoproteins; thickeners (eg, carboxyvinyl polymers); colorants (eg, titanium yellow, carsamine,
Safflower red) and the like.

The collagen production-promoting agent of the present invention absorbed from the skin enhances the productivity of collagen to maintain the skin tension holding structure composed of fibrous collagen in a favorable state,
This restores aging skin elasticity and elasticity, and keeps healthy skin in good condition. In addition, as a secondary effect, it enhances the moisturizing power of the skin and improves skin roughness.
Therefore, the cosmetic containing the collagen production promoter according to the present invention is extremely effective for maintaining youthful skin.

[0020]

The present invention will be described below in further detail with reference to examples.

Production Example 1 300 g of crushed dried leaves of licorice (Glycyrrhiza glabra)
Into 2000 ml of extraction solvent, and slowly stirring.
It was kept at 70 ° C. for hours. Thereafter, the mixture was filtered, and the filtrate was heated to 40 °
Under reduced pressure and dried with a vacuum drier to obtain a licorice leaf extract. When the above extraction was performed using four types of extraction solvents, the yield of the extract was as shown in Table 1.

[0022]

[Table 1] Sample No. Extraction solvent Extraction yield (% by weight) 1 Water 24.0 2 Methanol-water (1: 1 mixture) 21.7 3 Ethanol 12.7 4 Propanol-water (1: 1 mixture) Liquid) 14.3

Production Example 2 300 g of crushed licorice leaf same as that used in Production Example 1
2000 ml of 3-butylene glycol-water (1: 1 mixture)
And maintained at 80 ° C. for 3 hours while stirring, followed by filtration to obtain 1600 ml of an extract having a solid content of 3.84% by weight.
I got

Production Example 3 1750 ml of an extract having a solid content of 2.37% by weight was obtained in the same manner as in Production Example 2 except that the extraction solvent was changed to glycerin-water (1: 1 mixture).

Production Example 4 Extraction solvent was propylene glycol-water (1: 1 mixture)
1640 ml of an extract having a solid content of 3.62% by weight was obtained in the same manner as in Production Example 2 except that the above was changed.

Test Example 1: Test for Collagen Production Acceleration Test The following test method was used for the collagen production promoter comprising the licorice leaf extract according to Production Example 1 and the collagen production promoter comprising the licorice leaf extract according to Production Examples 2 to 4. Was used to test the effect of promoting collagen production.

Preparation of sample solution: Each sample was prepared at 0.05 M · Mcl
Dissolved in lvain buffer (pH 7.2) and changed concentration 2
Prepare different sample solutions. Test method: 48 2-month-old hairless mice (females) were divided into 8 groups of 6 mice each, and the back skin of each mouse was irradiated with 50 mJ / cm ² of ultraviolet (UV-B) light four times a week. For 6 weeks. Thereafter, 0.1 ml of a different sample solution for each group is applied to the UV-B irradiation site twice a day for 5 consecutive weeks (provided that the application date is 5 days per week). To the control group, the above buffer solution containing no sample is applied in the same manner.
Five weeks after the start of the application of the sample solution, a skin tissue of 1 cm × 1 cm was collected from the UV-B irradiation site, and 1 ml of 50 mM Tris-HCl buffer (pH 7.5, containing 1M-NaCl) was added thereto at 4 ° C.
And homogenize for 5 minutes and centrifuge. Collagen (salt-soluble collagen) in the obtained supernatant was subjected to Sircol C
Quantify using the ollagen Assay Kit (Biocolor). The percentage of the amount of collagen in the test group, based on the amount of collagen in the control group to which a buffer solution containing no sample was applied as a reference value, is defined as the collagen production promotion rate.

The test results are shown in Table 1. It was confirmed that the collagen production promoting agent of the present invention increased collagen production.

[0029]

TABLE 1 Collagen production promotion rate (%, Production Example 1) 0.1% solution 0.05% solution 0.025% solution 0.125% solution Sample 1 139.4 129.7--Sample 2 167.6 146.7- -Sample 3--163.4 148.9 Sample 4 158.1 137.2--

[0030]

Table 2 Collagen production promotion rate (%, Production Examples 2 to 4) 4% solution 2% solution Production Example 2 166.2 152.7 Production Example 3 158.9 146.7 Production Example 4 160.1 148.9

Test Example 2: Trial test An emulsion having the following composition and containing the sample 1 (ethanol extract of licorice leaves) according to Production Example 1 was prepared according to a conventional method. Licorice ethanol extract 1.0 g Cetyl alcohol 0.5 g Beeswax 2.0 g Polyoxyethylene sorbitan oleate (10E.O) 1.0 g Glyceryl monostearate 1.0 g Hyaluronic acid 0.1 g Propylene glycol 5.0 g Ethanol 3 0.0g Methyl parahydroxybenzoate 0.3g Fragrance 0.03 Purified water Remainder (total amount is 100ml)

A comparative example having the same composition as above except that the milky lotion of the present invention and the ethanol extract of licorice leaves were not prepared, was prepared by a conventional method of milky lotion production, and the following evaluation test was carried out.

Subjects: From a large number of women aged 21 to 41, 20 subjects who were judged as having rough skin corresponding to a score of 1 or 2 according to the evaluation criteria of the following judgment 1 were selected as subjects. Application test: To each subject, the emulsion of the present invention was applied to the right half of the face and the emulsion of the comparative example was applied to the left half once each morning and evening for 30 days.

[Judgment 1: Skin Roughness Improvement Effect] After the application test, a replica of the facial skin was taken using a replica method by Silflo (manufactured by FLEXICL DEVELOPMENTS LTD). Was observed, and the condition of the skin was determined according to the following evaluation criteria.

The score evaluation 1 Kawamizo-skin hill has turned up the consumption obtained, a wide range of the stratum corneum. (Rough skin condition) 2 Skin grooves / skins are unclear. The stratum corneum is partially turned up. (Rough skin condition) 3 Skin furrow / skin is observed but it is flat. (Normal skin) 4 Skin groove / skin is clear. (Relatively beautiful skin) 5 Skin grooves and hills are extremely clear and well-organized. (Beautiful skin)

The results are shown in Table 3. The area to which the emulsion of the present invention was applied was significantly improved in roughness as compared with the area to which the emulsion of the comparative example was applied.

[0037]

[Table 3] Example before the start of the evaluation test Comparative example of the emulsion application part Example 12 Emulsion application part 1 12 0 8 8 2 0 0 8 3 0 7 7 2 4 0 9 2 50 0 First name 0

[Judgment 2: Sensory evaluation] With respect to the feeling of use, all subjects were asked about the superiority and inferiority of the emulsion of the present invention and the comparative product. The total result of the answers is as shown in Table 5, and the sensory evaluation confirmed that the effect matched the evaluation result by the device and the excellent feeling of use.

[0039]

[Table 4] Evaluation items Examples Example products are good Comparative examples products are superior or inferior No skin familiarity 14 5 1 1 Moist 19 19 0 1 Skin growth 15 3 2 Satisfaction for improvement of rough skin 19 1 0 Satisfaction of skin color improvement 15 3 2 Improve the number and depth of wrinkles 19 1 0

Example 1 An emulsion having the following composition was produced by a conventional method. Jojoba oil 4 g Olive oil 2 g Squalane 2 g Cetanol 2 g Glyceryl monostearate 2 g Polyoxyethylene cetyl ether (20E.O) 2.5 g Polyoxyethylene sorbitan oleate (20E.O) 2 g 1,3-butylene glycol 3 g Paraoxybenzoic acid Methyl 0.15 g Fragrance 0.05 g Licorice leaf extract (Production Example 1 / Sample 2) 0.1 g Licorice leaf extract (Production Example 3) 1 g Purified water The remainder (total amount is 100 g)

Example 2 A lotion having the following composition was produced by a conventional method. Glycerin 3g 1,3-butylene glycol 3g Polyoxyethylene sorbitan oleate (20E.O) 0.5g Methyl parahydroxybenzoate 0.15g Citric acid 0.1g Sodium citrate 1g Flavor 0.05g Licorice leaf extract (Production example) 1. Sample 1) 0.2 g Licorice leaf extract (Production Example 3) 2 g Purified water Remainder (total amount is 100 g)

Example 3 A cream having the following composition was produced by a conventional method. Liquid paraffin 5 g Salamander beeswax 4 g Cetanol 3 g Squalane 10 g Lanolin 2 g Stearic acid 1 g Polyoxyethylene sorbitan oleate (20E.O) 1.5 g Glyceryl monostearate 3 g 1,3-butylene glycol 6 g Methyl paraoxybenzoate 1.5 g Flavoring agent 0.1 g Licorice leaf extract (Production example 1 / Sample 2) 0.1 g Licorice leaf extract (Production example 2) 1 g Purified water Remaining (total amount is 100 g)

Example 4 A pack having the following composition was produced by a conventional method. Polyvinyl alcohol 15 g Polyethylene glycol 3 g Propylene glycol 7 g Ethanol 10 g Ethyl parahydroxybenzoate 0.05 g Fragrance 0.05 g Licorice leaf extract (Production Example 4) 5 g Purified water The remainder (total amount is 100 g)

[0044]

As described above, the collagen production promoter of the present invention not only has an excellent collagen production promoting effect, but also has an excellent feeling in use and safety. It is suitable for blending into a general skin external preparation such as a cosmetic as a component for maintaining the condition.

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[Procedure amendment]

[Submission date] December 28, 1998 (1998.12.
28)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0038

[Correction method] Change

[Correction contents]

[Judgment 2: Sensory evaluation] With respect to the feeling of use, all subjects were asked about the superiority and inferiority of the emulsion of the present invention and the comparative product. The total result of the answers is as shown in Table 4 , and the sensory evaluation confirmed the effect and the excellent feeling of use that matched the evaluation result by the device.

Continuation of the front page (51) Int.Cl. ⁷ Identification code FI Theme coat II (reference) A61P 43/00 A61K 31/00 643D A61K 35/78 35/78 J F term (reference) 4C083 AA082 AA111 AA112 AA122 AC022 AC072 AC102 AC122 AC182 AC242 AC302 AC422 AC442 AC482 AD042 AD112 AD512 CC02 CC04 CC05 EE12 4C088 AB59 AC05 BA08 CA06 MA28 MA63 ZA89

Claims (3)

[Claims] 1. A collagen production promoter comprising a substance extracted from licorice leaves and having a function of promoting collagen production by skin fibroblasts. 2. An extract obtained by extracting licorice leaves using a solvent selected from the group consisting of water, methanol, ethanol, propanol, 1,3-butylene glycol, glycerin, propylene glycol or a mixture thereof. An agent for promoting collagen production, comprising a substance as an active ingredient. 3. An external preparation for skin comprising the collagen production promoter according to claim 1 or 2.