KR20150014022A - Cosmetic composition for wrinkle improvement comprising atractylenolide Ⅲ as effective component - Google Patents

Abstract

The present invention relates to a cosmetic composition for alleviating wrinkle comprising atractylenolide III as an effective component, and more specifically, to a cosmetic composition for alleviating wrinkle comprising atractylenolide II or salt thereof as an effective component. The atractylenolide III of the present invention has excellent inhibition ability of expression of MMP-1, no cytotoxicity, and excellent wrinkle improvement effect, thereby being used as a functional material for alleviating and preventing wrinkle.

Description

TECHNICAL FIELD The present invention relates to a cosmetic composition for wrinkle improvement comprising atractylenolide III as an effective ingredient,

The present invention relates to a cosmetic composition for improving skin wrinkles containing atactylenolide III as an active ingredient, and more particularly to a cosmetic composition for improving skin wrinkles containing atractylenolide (III) compound or a salt thereof as an active ingredient And more particularly to a cosmetic composition for cosmetics.

Collagen is a major substrate protein produced in the fibroblasts of the skin. It is an important protein in the epilepsy of the cell and accounts for 30% of the total weight of the bioprotein. It has a solid triple helix structure. The main functions of collagen are known as mechanical firmness of skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, induction of cell division and differentiation. It is known that wrinkles are caused by decreased collagen synthesis ability in the dermis of the skin or decreased amount of collagen due to promotion of collagen degradation. Accordingly, a method for promoting collagen synthesis or suppressing collagen degradation has been attempted as a method for improving wrinkles.

The secretion of cytokines such as TNF-α from keratinocytes is greatly increased by external stimuli such as ultraviolet light and the collagenase of fibroblast (TNF-α) Matrix Metallo Proteinase (MMP-1) expression is increased, leading to wrinkles as collagen decomposition increases in the dermis. Collagenase is a zinc-dependent endopeptidase secreted from cells, such as polymorphonuclear neutrophils, macrophages and fibroblasts. It acts at neutral pH and acts as a substrate It is divided into collagenases, gelatinases, stromelysins, matrilysins and membrane-type MMP by their selectivity and structural similarity. In skin, MMP-1, MMP-2 and MMP-9 are involved in various enzymes. MMP-1 is the most essential enzyme involved in collagen degradation. Therefore, there is a desperate need to develop a new skin external preparation which can suppress wrinkle formation fundamentally by inhibiting the decomposition of collagen produced by inhibiting the expression of MMP-1 or inhibiting its activity, and being safe to living body.

Korean Patent Laid-Open Publication No. 2013-0066874 discloses a compound useful in the prevention or treatment of irritable bowel syndrome comprising atractylenolide III as an active ingredient and a composition comprising the same, There has been no known cosmetic composition for improving skin wrinkles containing atactylenolide III as an effective ingredient.

The present invention has been made in view of the above-mentioned needs, and it is an object of the present invention to provide atractylenolide (III) to a human-derived fibroblast that induces the production of collagenase MMP-1 by adding TNF- As a result, it has been found that Artactylenolide III is safe and can be used as a cosmetic composition for improving the wrinkles of skin which is excellent in the effect of improving the wrinkles of the skin, as it not only shows excellent inhibitory effect on MMP-1 expression, but also does not show cytotoxicity. Respectively.

In order to achieve the above object, the present invention provides a cosmetic composition for improving skin wrinkles containing an atractylenolide (III) compound or a salt thereof as an active ingredient.

The artactylenolide III of the present invention is excellent in the inhibitory effect on expression of MMP-1, has no cytotoxicity, and is excellent in the effect of improving skin wrinkles. Therefore, it can be usefully used as a functional material for improving and preventing wrinkles on the skin.

In order to achieve the object of the present invention, the present invention provides a cosmetic composition for improving skin wrinkles containing an atractylenolide (III) compound represented by the following formula (1) or a salt thereof as an active ingredient.

The atractylenolide (III) compound of the present invention can be extracted and purified using suitable processes known to those skilled in the art, and preferably selected from the group consisting of Curcuma aromatica , Curcuma longa , atractylodes spp.) plant, and more preferably purified from extracts from Atractylodes macrocephala, but is not limited thereto.

On the other hand, the collagen of the dermal layer is decomposed by increasing the expression amount of Matrix Metallo Proteinase (MMP-1) of fibroblast by the action of cytokine TNF-a in fibroblast. The atractylenolide III compound or its salt inhibits the expression of collagenase (Matrix Metallo Proteinase, MMP-1), which is increased by cytokine TNF-α. As described above, the atractylenolide (III) compound or its salt is effective for inhibiting the collagen degradation mediated by the action of TNF-α and the generation of skin wrinkles. Therefore, the cosmetic composition containing the same, Can be effectively used.

In the cosmetic composition for improving skin wrinkles according to an embodiment of the present invention, the atractylenolide III compound or a salt thereof may be 0.000001 to 10% by weight, preferably 0.0001 to 10% by weight, 1.0% by weight.

In addition, an acceptable salt of atractylenolide III may be formed. The acceptable salt generally means a non-toxic salt capable of forming an alkali metal salt and an acid addition salt or base addition salt. Such salts include organic or inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, sulfamic acid, acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, hexanoic acid, cyclopentylpropionic acid, glycolic acid, (4-hydroxybenzoyl) benzoic acid, cinnamic acid, cinnamic acid, mandelic acid, phthalic acid, maleic acid, maleic acid, fumaric acid, tartaric acid, But are not limited to, acetic acid, lauric acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4- chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butyl acetic acid, lauryl sulfuric acid, gluconic acid , Benzoic acid, glutamic acid, hydroxynaphthoic acid, Acid addition salts formed with salicylic acid, stearic acid, cyclohexylsulfamic acid, quinic acid or muconic acid, and the like; (For example, an alkali metal ion, an alkaline earth metal ion or an aluminum ion), an alkali metal or an alkaline earth metal hydroxide (for example, sodium, potassium, calcium, magnesium, And barium hydroxide), substituted with ammonia, or substituted with organic bases such as aliphatic, alicyclic or aromatic organic amines such as ammonia, methylamine, dimethylamine, diethylamine, picoline, ethanolamine, diethanolamine, triethanol Or a pharmaceutically acceptable salt thereof is selected from the group consisting of amine, ethylenediamine, lysine, arginine, ornithine, choline, N, N'-dibenzylethylenediamine, chloroprocaine, diethanolamine, procaine, N-benzylphenethylamine, , Tris (hydroxymethyl) -aminomethane or salts formed when coordinating with tetramethylammonium hydroxide, and the like.

Examples of the salt include sodium, potassium, calcium, magnesium, ammonium or tetraalkylammonium salts. When the compound contains basic functional groups, salts with non-toxic organic acids or inorganic acids such as hydrohalides (for example, Chloride or hydrobromide), sulfate, phosphate, sulfamate, nitrate, acetate, trifluoroacetate, trichloroacetate, propionate, hexanoate, cyclopentylpropionate, glycolate, glutarate, (4-hydroxybenzoyl) fumarate, tartarate, tartrate, malate, succinate, ascorbate, malate, maleate, fumarate, tartrate, citrate, benzoate, Citrate, benzoate, 3- (4-hydroxybenzoyl) benzoate, picrate, cinnamate, Mandel Methanesulfonate mesylate), ethanesulfonate, 1,2-ethane-disulfonate, 2-hydroxyethanesulfonate, benzenesulfonate (besylate), 4-chlorobenzenesulfonate , 2-naphthalenesulfonate, 4-toluenesulfonate, camphorate, camphorsulfonate, 4-methylbicyclo [2.2.2] -oct-2-ene-1-carboxylate, glucoheptonate, 3- Phenyl propionate, trimethyl acetate, tert-butyl acetate, lauryl sulfate, gluconate, benzoate, glutamate, hydroxynaphthoate, salicylate, stearate, cyclohexyl sulfamate, quinate or muconate Salts, and the like.

In the cosmetic composition according to one embodiment of the present invention, the cosmetic composition for improving skin wrinkles may be used as an external ointment for skin, a cream, a softening longevity, a nutritional lotion, a pack, an essence, a hair tonic, a shampoo, a rinse, a hair conditioner, Gel, skin lotion, skin softener, skin toner, astringent, milky lotion, milk lotion, moisturizing lotion, nutrition lotion, massage cream, nutritional cream, eye cream, moisturizing cream, hand cream, makeup base, foundation, nutrition essence, line But are not limited to, a formulation selected from the group consisting of a screen, a line oil, a soap, a cleansing foam, a cleansing lotion, a cleansing cream, a liquid cleanser, a bathing agent, a body lotion and a body cleanser. The composition of each of these formulations may contain various kinds of bases and additives necessary for formulation of the formulation, and the kinds and amounts of these ingredients can be easily selected by those skilled in the art.

When the formulation of the present invention is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.

In the case of the solution or emulsion of the present invention, a solvent, a solvent or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component is selected from aliphatic alcohol sulfates, aliphatic alcohol ether sulfates, sulfosuccinic acid monoesters, isethionates, imidazolinium derivatives, methyltaurate, sarcosinates, fatty acid amides Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolenic derivatives or ethoxylated glycerol fatty acid esters.

The formulation of the present invention may further contain an excipient including a fluorescent substance, a fungicide, a hygroscopic substance, a humidifier, a fragrance, a fragrance carrier, a protein, a solubilizing agent, a sugar derivative, a sunscreen, a vitamin, .

As described above, when the cosmetic composition for improving skin wrinkles is formulated into pharmaceuticals or cosmetics, it may contain known excipients applicable to the skin acting as a carrier for the active ingredient. When formulating into pharmaceuticals, reference is made to the disclosure of [Remington ' s Pharmaceutical Science, Mack Publishing Company, Easton PA], and in formulation into cosmetics, International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association, Inc., Washington, 1995). Which are incorporated herein by reference.

In the cosmetic composition according to one embodiment of the present invention, the cosmetic composition for improving skin wrinkles contains an additive selected from the group consisting of water, a surfactant, a moisturizer, a lower alcohol, a chelating agent, a bactericide, an antioxidant, an antiseptic, And these additives may introduce, but are not limited to, those commonly used in the cosmetic or dermatological fields.

Hereinafter, the present invention will be described in detail by way of examples. However, the following examples and formulations are illustrative of the present invention, and the content of the present invention is not limited to the following examples and prescription examples.

Example  One: Atactylenolide  In fibroblasts of the < RTI ID = 0.0 & MMP -1 expression inhibition

In order to examine the inhibitory effect of the artactylenolide III of the present invention on the expression of the collagenolytic enzyme, a commercially available artactylenolide III (Sequoia Research Products Limited, UK, Cat. No. SRP01375d) was added to a culture solution of human- Compounds were added to test the effect of inhibiting MMP-1 expression at the cellular level.

Human-derived fibroblasts were inoculated into a 48-well microplate to a concentration of 1 × 10 ⁶ cells per well. After the addition of atactylenolide III to the medium in DMEM medium, the cells were pretreated at 37 ° C. for 24 hours, α (10 ng / ml) and the medium containing the test substance, followed by further incubation for 24 hours. At this time, resveratrol was used as a positive control group.

After which the human MMP-1 is the reaction of a 96-well plate and the culture medium is coated at 4 ℃ - using after the culture collection of the supernatant of each well MMP-1 diagnostic kit (RayBio ^® human MMP-1 ELISA kit) wherein The reaction mixture was reacted with MMP-1 antibody and HRP-streptavidin in the presence of tetramethylbenzidine, and the absorbance at 450 nm was measured to determine the amount of newly synthesized MMP-1 The relative inhibition of MMP-1 production in the control group was calculated to analyze the ability to inhibit the expression of collagenase (Table 1).

Effect of the present invention on the inhibition of MMP-1 expression of atactylenolide III sample The amount of MMP-1 (Abs 450 nm) Expression inhibition rate (%) Control group (no addition) 0.302 + 0.045 - TNF-α 10 ng / ml 0.350 + 0.038 TNF-α 10 ng / ml +
Atactylenolide III 0.0005% 0.321 + 0.033 8.28% TNF-α 10 ng / ml +
Atactylenolide III 0.001% 0.281 + 0.042 19.71% TNF-α 10 ng / ml +
Atactylenolide III 0.005% 0.237 + 0.038 32.29% TNF-α 10 ng / ml +
Atactylenolide III 0.01% 0.201 + 0.050 42.57%

As a result of analysis of inhibitory effect of artactylenolide III of the present invention on the expression of collagenolytic enzyme, it was found that the expression of highly potent MMP-1 in human-derived threonine cells at a concentration of 0.01 wt% Inhibitory effect.

Prescription example  1: ointment

Table 2 shows prescription examples of the external ointment formulation for skin wrinkle improvement and treatment containing artactylenolide III of the present invention.

A composition for external skin ointment containing Artactylenolide III of the present invention as an active ingredient Composition Production Example 1 (% by weight) Comparative Example 1 - Atactylenolide III
- diethyl sebacate
- Writers
- polyoxyethylene oleyl ether phosphate
- Sodium benzoate
-vaseline 3.0
8
5
6
Suitable amount
to 100 -
8
5
6
Suitable amount
to 100

Prescription example  2: Cream

Table 3 shows prescription examples of cream formulations in cosmetic compositions for improving skin wrinkles containing artactylenolide III of the present invention.

The composition of the cream formulation containing the artactylenolide III of the present invention as an active ingredient Composition Production Example 2 (% by weight) Comparative Example 2 - Atactylenolide III
- Stearic acid
- Cetanol
- potassium hydroxide
-glycerin
- propylene glycol
-antiseptic
-incense
-Purified water 0.5
15.0
1.0
0.7
5.0
3.0
Suitable amount
Suitable amount
to 100 -
15.0
1.0
0.7
5.0
3.0
Suitable amount
Suitable amount
to 100

Prescription example  3: Softening longevity

Table 4 shows prescription examples of the formulation for softening longevity in cosmetic compositions for improving skin wrinkles containing atactylenolide III of the present invention.

The formulation of the softening longevity formulation containing the atactylenolide III of the present invention as an active ingredient Composition Production Example 3 (% by weight) Comparative Example 3 - Atactylenolide III
- ethanol
- polyoxyethylene sorbitan polylauric acid
- Paraoxybenzoic acid methyl
-glycerin
-1,3-butylene glycol
-incense
- Pigment
-Purified water 0.05
10.0
1.0
0.2
5.0
6.0
Suitable amount
Suitable amount
to 100 -
10.0
1.0
0.2
5.0
6.0
Suitable amount
Suitable amount
to 100

Prescription example  4: Nourishing lotion

Table 5 shows prescription examples of the nutritional lotion formulation among the cosmetic compositions for improving skin wrinkles containing atactylenolide III of the present invention.

The composition of the nutritional lotion formulation containing the atactylenolide III of the present invention as an active ingredient Composition Production Example 4 (% by weight) Comparative Example 4 - Atactylenolide III
- Vaseline
- sesquioleic acid sorbitan
- polyoxyethylene oleyl ethyl
- Paraoxybenzoic acid methyl
- propylene glycol
-ethanol
-Carboxyvinyl polymer
- potassium hydroxide potassium
- Pigment
-incense
-Purified water 0.1
2.0
0.8
1.2
Suitable amount
5.0
3.2
18.0
0.1
Suitable amount
Suitable amount
to 100 -
2.0
0.8
1.2
Suitable amount
5.0
3.2
18.0
0.1
Suitable amount
Suitable amount
to 100

Prescription example  5: Pack

Table 6 shows prescription examples of pack formulations among cosmetic compositions for improving skin wrinkles containing atactylenolide III of the present invention.

A pack formulation containing the atactilylenolide III of the present invention as an active ingredient Composition Production Example 5 (% by weight) Comparative Example 5 - Atactylenolide III
- glycerin
- propylene glycol
- Polyvinyl alcohol
-ethanol
- polyoxyethylene oleyl ether
- Paraoxybenzoic acid methyl
-incense
- Pigment
-Purified water 0.01
0.5
5.0
4.0
15.0
8.0
0.2
Suitable amount
Suitable amount
to 100 -
5.0
4.0
15.0
0
1.0
0.2
Suitable amount
Suitable amount
to 100

Prescription example  6: Nutritional essence

Table 7 shows prescription examples of nutritional essence formulations among cosmetic compositions for improving skin wrinkles containing artactylenolide III of the present invention.

The composition of the nutritional essence formulation containing the atactylenolide III of the present invention as an active ingredient Composition Production Example 6 (% by weight) Comparative Example 6 - Atactylenolide III
- propylene glycol
-glycerin
- aqueous solution of sodium hyaluronate (1%)
-ethanol
- Polyoxyethylene hardened castor oil
- Paraoxybenzoic acid methyl
-incense
-Purified water 1.0
10.0
10.0
5.0
5.0
1.0
0.1
Suitable amount
to 100 -
10.0
10.0
5.0
5.0
1.0
0.1
Suitable amount
to 100

Example  2: Atactylenolide  Through panel test of Ⅲ Cosmetics  Wrinkle improvement test of cream

 In order to analyze the wrinkle-reducing effect of the art lactylenolide III of the present invention, it was confirmed that the cosmetic cream prepared in Preparative Example 2 and Comparative Example 2 containing atactylenolide III as an active ingredient, Panel tests were conducted.

30 healthy women from 35 to 50 years old were divided into two groups of 15 persons, the cream of Comparative Example 2 was applied to Group 1 and the cream of Preparation Example 2 was applied to the face portion twice a day for three months , And the degree of improvement of the wrinkles of the skin after 3 months was evaluated by the questionnaire of the subject. The questionnaire of the subject was judged to be three stages of no improvement, little improvement, and considerable improvement in comparison with before use in regard to improvement of skin wrinkles and elasticity, and the results were examined as shown in Table 8.

The effect of the cosmetic cream containing the atactylenolide III of the present invention as an active ingredient on the skin wrinkle-improving effect sample No improvement Slight improvement A significant improvement Comparative Example 2 8 6 One Production Example 2 2 7 6

As a result of investigating the wrinkle-reducing effect of the artactylenolide III of the present invention, it was found that the effect of improving the skin wrinkles was remarkably excellent when the cream of Preparation Example 2 was used as compared with Comparative Example. In addition, since skin irritation or side effects of the cosmetic cream of the present invention were not found in the skin wrinkle improving test procedure of Example 2, artactylenolide III of the present invention is safe for human body and excellent in wrinkle of skin , Which can be useful as a functional material for improving and preventing skin wrinkles.

Claims (4)

A cosmetic composition for improving skin wrinkles containing an atractylenolide (III) compound represented by the following formula (1) or a salt thereof as an active ingredient.
[Chemical Formula 1]

The cosmetic composition for improving skin wrinkles according to claim 1, wherein the atractylenolide (III) compound or salt thereof is contained in an amount of 0.000001 to 10% by weight based on the total weight of the composition. The cosmetic composition according to claim 1 or 2, wherein the cosmetic composition is at least one selected from the group consisting of an ointment for external use, a cream, a softening agent, a nutritional lotion, a pack, an essence, a hair tonic, a shampoo, a rinse, a hair conditioner, a hair treatment, Soap, Skin Toner, Astringent, Milk, Lotion, Milk Lotion, Moisture Lotion, Nutrition Lotion, Massage Cream, Nourishing Cream, Eye Cream, Moisture Cream, Hand Cream, Makeup Base, Foundation, Nutrition Essence, Sunscreen, Sun Oil, Soap , A cleansing foam, a cleansing lotion, a cleansing cream, a liquid cleansing agent, a bathing agent, a body lotion and a body cleanser. The cosmetic composition according to any one of claims 1 to 3, wherein the cosmetic composition is at least one selected from the group consisting of water, a surfactant, a moisturizer, a lower alcohol, a chelating agent, a bactericide, an antioxidant, an antiseptic, The cosmetic composition for improving skin wrinkles, further comprising an additive.