KR102084559B1 - Cosmetic Composition for Improving Skin Wrinkle Containing Derivatives of Ginsenoside Rh2 - Google Patents

Abstract

The present invention relates to a composition for alleviating skin wrinkles containing a ginsenoside Rh2 derivative or a salt thereof. Since the ginsenoside Rh2 derivative has an effect of promoting collagen synthesis, the composition of the present invention alleviates skin wrinkles, improves skin elasticity, and regenerates skin.

Description

Cosmetic composition for improving skin wrinkles, including ginsenoside Rh2 derivatives {{Cosmetic Composition for Improving Skin Wrinkle Containing Derivatives of Ginsenoside Rh2}

The present invention relates to a cosmetic composition for improving skin wrinkles comprising a ginsenoside Rh2 derivative.

As the skin ages, aging worsens. Skin over long period of time Exposure causes changes in the epidermis and dermis tissue, leading to increased wrinkles, thickening of the skin, loss of elasticity, and roughness and spots. As such skin aging can be delayed by enhancing collagen synthesis, studies are being actively conducted to develop substances that are safe for the living body while enhancing collagen synthesis.

Collagen is a major constituent of the extracellular matrix and is the major substrate protein produced in the fibroblasts of the skin. It is also an important protein, accounting for about 30% of the total weight of biological proteins, and has a solid triple helix structure. Collagen forms most of the organic matter in the skin, tendons, bones and teeth, especially in bones and skin. Most other body structures exist as fibrous inclusions.

The main functions of collagen are known as mechanical firmness of skin, resistance of connective tissue and binding of tissue, support of cell adhesion, induction of cell division and differentiation (in organic growth or wound healing). In recent years, extensive research on skin aging has revealed an important function of collagen in the skin. For example, collagen is reduced by photoaging by age and ultraviolet irradiation, which is known to be closely related to wrinkle formation of the skin. Collagen also plays an important role in wound healing and promotes the synthesis of collagen in the damaged epithelium so that wounds can be recovered quickly and without scars. As described above, if collagen metabolism is promoted by promoting collagen synthesis, the components of the dermal matrix are increased, and thus the effects of wrinkle improvement, elasticity enhancement, skin strengthening and wound healing can be expected.

In order to obtain such effects, conventionally, products using collagen have been released in order to take advantage of the skin wrinkle improvement effect of collagen, but these cosmetics apply collagen to the skin surface, and it is difficult to absorb percutaneous polymer collagen, which is difficult to wrinkle. Because no improvement could be expected, it could not be said to be an essential skin function improvement.

Therefore, interest in substances that can promote collagen synthesis in the skin itself has increased, and conventionally, substances capable of promoting collagen synthesis include retinoic acid, transforming growth factor (TGF), and chlorella extract. Known. However, retinoic acid is unstable and there is a limit to the amount of use due to stability problems such as irritation, redness, etc. when applying the skin, chlorella extract, etc. are insignificant, and can not be expected to substantially improve the skin function by promoting collagen synthesis of the skin. Therefore, there is a need for the development of a new collagen synthesis promoter that is safe for the living body and is more effective than the existing collagen synthesis promoter.

In order to suppress such wrinkles or to slow the progression of the skin, cosmetics or skin protectants containing various skin protection ingredients such as retinol, retinoids, vitamin C, flavonoids and tocopherol have been developed. In the final formulation, the potency is low, the efficacy is slight, and the skin irritation has a serious problem. Therefore, there is a need for the development of a material that exhibits the effect of improving skin aging by reducing skin wrinkles.

Ginsenosides have been reported to have anticancer effects, immune enhancing effects, and anti-fatigue effects. Patent Document 1, as a means for solving the difficulty in quality control including reproducibility because ginsenoside composite material has a lot of components other than ginsenoside, containing various ginsenosides, including ginsenoside Rh2 in a predetermined amount A composition is disclosed, and the effect of treating the lung cancer of the composition is disclosed. As described above, although the anticancer effect of the mixture containing ginsenoside Rh2 is disclosed, a technique of introducing a substituent to ginsenoside Rh2 has not been confirmed in order to increase the skin wrinkle improving effect.

In addition, even if the compound having excellent physiological effects may be cytotoxic when used as a single component instead of a mixture, it is necessary to confirm whether the compound is safe when using the compound as a functional component.

Korean Registered Patent No.892764

An object of the present invention is to provide a high safety material with less cytotoxicity while improving wrinkle symptoms of the skin.

In order to solve the above problems, the present invention is a cosmetic composition for improving wrinkles of the skin comprising a ginsenoside Rh2 derivative, or a salt thereof; Cosmetic composition for enhancing elasticity of the skin, including ginsenoside Rh2 derivatives, or salts thereof; And it provides a cosmetic composition for skin regeneration comprising a ginsenoside Rh2 derivative, or a salt thereof.

The ginsenoside Rh2 derivative of the present invention promotes collagen synthesis and has low cytotoxicity, so that high content treatment can be performed for the purpose of promoting collagen synthesis. Therefore, ginsenoside Rh2 derivative can be used for skin wrinkle improvement, skin elasticity improvement, and skin regeneration.

1 is a cytotoxicity evaluation results of ginsenoside Rh2 derivatives; Untreated: untreated sample, 10% FBS +: untreated, 10% FBS added. 20, 10, 5, 2, 1: Ginsenoside Rh2, or ginsenoside Rh2 derivative treatment concentration (unit: µg / ml).
2 shows collagen synthesis evaluation results of ginsenoside Rh2 derivatives.

Hereinafter, the present invention will be described in detail.

The present invention relates to the use of ginsenoside Rh2 derivatives for skin improvement.

Ginsenoside Rh2 is represented by the following formula:

.

.

Ginsenoside Rh2 derivatives are made based on the chemical formula of the above ginsenoside Rh2. The ginsenoside Rh2 derivative may be a substituent introduced at a carbon position of the ginsenoside Rh2 formula, preferably a substituent may be introduced at a 20th to 27th carbon position, and more preferably a 24th carbon. The substituent may be introduced to the 27th carbon position, and most preferably, the substituent may be introduced at the 25th carbon position, but is not limited thereto.

Ginsenoside Rh2 derivative of the present invention may be one having the following formula.

In the above formula, R may be one selected from the group consisting of hydrogen, a hydroxyl group, and an alkyl group having 1 to 5 carbon atoms, and the alkyl group having 1 to 5 carbon atoms may be a hydroxyalkyl group. In the above formula, R may preferably be a hydroxyl group or a hydroxyalkyl group having 1 to 5 carbon atoms, more preferably a hydroxyl group.

In one embodiment of the present invention, when 25-hydroxy ginsenoside Rh2 (25-Hydroxy ginsenoside Rh2) is treated to dermal fibroblasts as a ginsenoside Rh2 derivative, cytotoxicity is lower than that of ginsenoside Rh2 and cytotoxic. In the high concentration treatment without the collagen synthesis effect was better than ginsenoside Rh2.

Ginsenoside Rh2 derivatives can also be used in the form of their salts. The salts are not particularly limited and include both acid and base addition salts. Exemplary salts include sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, isonicotinate, lactate, salicylate, tartrate, oleate, tannate , Pantothenate, bitartrate, ascorbate, succinate, maleate, fumarate, gluconate, glucuronate, saccharide, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzene Sulfonates, and p-toluenesulfonates, including but not limited to these.

Ginsenoside Rh2 derivatives may be synthesized and used according to methods known in the art, and may be commercially available. In addition, ginsenoside Rh2, which is a raw material for preparing a ginsenoside Rh2 derivative, may be obtained from ginseng extract. The type of ginseng used at this time is not particularly limited, and ginseng, red ginseng, white ginseng, taeguksam, misam and the like can be used. In addition, the ginseng extract is contained not only in the leachate obtained by leaching and transferring from ginseng, but also in the concentrate obtained by partially or fully concentrating the leachate, or in stagnation, premises, regular and flow extracts prepared by drying the concentrate again. Of course, the chemicals that exert include all of the plant itself, and extracts from all parts of ginseng such as stems, roots, leaves, flowers, fruits are usable and are not limited to extracts of any particular part. In addition, a method for extracting ginsenoside Rh2 from ginseng extract may use a known method.

The present invention is a cosmetic composition for improving wrinkles of the skin comprising a ginsenoside Rh2 derivative, or a salt thereof, a ginsenoside Rh2 derivative, or a cosmetic composition for enhancing the elasticity of the skin comprising a salt thereof, a ginsenoside Rh2 derivative, or It provides any one selected from the group consisting of a cosmetic composition for skin regeneration comprising a salt thereof. The use may be used independently or in combination with other uses, but is not limited thereto.

The main functions of skin fibroblasts include damaged skin tissue regeneration through extracellular matrix synthesis and proliferation. Exogenous aging factors such as photoaging, or endogenous aging factors due to accumulation of damage by free oxygen, aging of cells due to telomeres, and the like decrease the physiological activity of skin fibroblasts in the dermal layer. Collagen accounts for more than 95% of the extracellular matrix of the skin and plays a very important part in the physiological activity of fibroblasts through interactions and signal exchanges with cell adhesion molecules and cytoskeleton. When the synthesis of collagen is reduced, the amount of collagen in the skin tissue is reduced, thereby reducing the surface tension, thereby reducing skin elasticity and forming skin wrinkles, as well as physiologically active functions including cell proliferation and regeneration functions. It causes a decreasing vicious cycle.

Therefore, collagen of skin fibroblasts may be directly related to the repair or regeneration of tissue during skin regeneration, skin elasticity, skin wrinkle formation and skin damage. That is, if the synthesis of collagen or procollagen of skin fibroblasts is promoted, skin wrinkle improvement, skin elasticity improvement, repair and regeneration of damaged skin tissues; And skin aging prevention. Cosmetic compositions comprising the ginsenoside Rh2 derivative of the present invention promotes collagen synthesis, thereby improving skin wrinkles, enhancing skin elasticity, repairing and regenerating damaged skin tissue; And anti-aging of skin.

In an embodiment of the present invention, when the ginsenoside Rh2 derivative is treated to dermal fibroblasts, collagen synthesis effect is remarkably superior to that of ginsenoside Rh2, and cytotoxicity is low. Since the ginsenoside Rh2 derivative of the present invention does not affect the proliferation of skin fibroblasts and promotes collagen synthesis, the ginsenoside Rh2 derivative can be used for improving skin function.

The content of the ginsenoside Rh2 derivative of the present invention is 0.0001-20% by weight based on the total weight of the cosmetic composition, preferably 0.5-20%, more preferably 1.0-20% by weight. When the content of the ginsenoside Rh2 derivative is less than 0.0001% by weight, skin wrinkle improvement, skin elasticity improvement, repair and regeneration of damaged skin tissues by the ginsenoside Rh2 derivative are greatly reduced, and the content exceeds 20% by weight. May cause skin irritation and may result in formulation problems.

Cosmetic compositions of the present invention may be prepared in liquid or solid form using bases, adjuvants and additives commonly used in the cosmetic art. Cosmetics in liquid or solid form may include, for example, but not limited to forms such as lotion, cream, lotion, bath.

Bases, adjuvants and additives commonly used in the cosmetic field are not particularly limited and include, for example, water, alcohols, propylene glycol, stearic acid, glycerol, cetyl alcohol, liquid paraffin and the like.

The cosmetic composition of the present invention may include ginsenoside Rh2 derivatives, as well as components commonly used in cosmetic compositions, such as conventional auxiliaries such as antioxidants, stabilizers, solubilizers, vitamins, pigments and flavorings, and Carrier may be included.

Cosmetic compositions of the invention may be prepared in any formulations conventionally prepared in the art, including, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing , Oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like, but are not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

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

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, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethyleneglycol or sorbitan.

When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide ether sulfate, an alkyl Amidobetaines, fatty alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

The cosmetic composition of the present invention may be used alone or in duplicate, or may be used in combination with other cosmetic compositions other than the present invention. In addition, the cosmetic composition according to the present invention may be used according to a conventional method of use, and the number of times of use may vary depending on the skin condition or taste of the user.

When the cosmetic composition of the present invention is a soap, a surfactant-containing cleansing or a surfactant-free cleansing formulation, it may be wiped off, peeled off or washed with water after application to the skin. As a specific example, the soap is liquid soap, powdered soap, solid soap and oil soap, the surfactant-containing cleansing formulation is a cleansing foam, cleansing water, cleansing towels and cleansing pack, the surfactant-free cleansing formulation is a cleansing cream , Cleansing lotion, cleansing water and cleansing gel, but are not limited thereto.

Hereinafter, the present invention will be described in detail by production examples and examples.

However, the following Preparation Examples and Examples are only for illustrating the present invention, and the content of the present invention is not limited by the following Preparation Examples and Examples.

Experimental Example 1. Cytotoxicity evaluation of ginsenoside Rh2 derivative (25-Hydroxy ginsenoside Rh2, hereinafter referred to as 'ginsenoside Rh2 derivative')

In order to confirm cytotoxicity, MTT reduction method (3 (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide reduction method) was performed. Specifically, human fibroblasts (ATCC 2076) were dispensed into 24-well plates at a density of 1 × 10 ⁵ cells using DMEM medium (Gibco, USA) containing 10% bovine serum. After 1 day, ginsenoside Rh2 or ginsenoside Rh2 derivative (Ambo Research Institute) was added to the medium, and the medium was replaced with fresh medium (DMEM, 0% bovine serum 0%), respectively. Fibroblasts were treated at a concentration of 2 μg / ml and 1 μg / ml, and then cultured at 37 ° C. for 24 hours. At this time, a sample which was not treated with ginsenoside Rh2 or a ginsenoside Rh2 derivative was used as a negative control group. In addition, the sample which did not process ginsenoside Rh2 or a ginsenoside Rh2 derivative was made into the normal group. Thereafter, the cells were washed with PBS, and 1 ml of a diluted solution diluted 10-fold with MTT (2.5 mg / ml) was added to DMEM medium, followed by incubation at 37 ° C for 4 hours. After the incubation was completed, the medium was removed, and 0.5 ml of DMSO was completely dissolved for 10 minutes at room temperature, and then absorbance was measured at 570 nm. The absorbance measurement result is shown in FIG.

As can be seen in Figure 1, the treatment of ginsenoside Rh2 derivatives did not show cytotoxicity in the concentration range of 1 ~ 20㎍ / ㎖. On the other hand, the treatment with ginsenoside Rh2 was confirmed to exhibit cytotoxicity at concentrations of 2 μg / ml or more.

From the above results, it was found that confirming the cytotoxicity before using the physiological effect of the compound, and ginsenoside Rh2 derivatives do not show cytotoxicity even at high concentrations, so high content treatment is required to increase collagen synthesis ability. I could see what was possible.

Experimental Example 2 Evaluation of Collagen Synthesis of Ginsenoside Rh2 Derivatives

The anti-wrinkle effect of ginsenoside Rh2 derivatives was evaluated through collagen synthesis evaluation of human skin fibroblasts. Dermal fibroblasts (ATCC, USA) were dispensed 1 × 10 ⁵ in 24 well plates. DMEM: F12 mixed medium containing 10% bovine serum was treated and incubated in a 37 ° C., 5% CO ₂ incubator. After 24 hours, ginsenoside Rh2 was treated at concentrations of 1 μg / ml and 2 μg / ml, which were not cytotoxic. Ginsenoside Rh2 derivatives were 1 μg / ml, 5 μg / ml, 10 Treatment was at a concentration of μg / ml, 20 μg / ml. As a positive control, ascorbic acid (L-ascorbic acid) was treated at a concentration of 50 ㎍ / ml. After 24 hours of sample treatment, only the supernatant was separated and the procollagen (procollagen) was observed using a procollagen type (I) ELISA kit (Takara, Japan) in the supernatant. Collagen synthesis ability results are shown in FIG.

As a result of confirming collagen synthesis ability of the ginsenoside Rh2 derivative treatment group, collagen synthesis was promoted more than 20% compared to the sample untreated group at a concentration of 10 μg / ml or more. On the other hand, in the Ginsenoside Rh2 treatment group, collagen was synthesized at a concentration of 2 ㎍ / ml, which showed no cytotoxicity, but was very low, less than 10% compared to the sample untreated group, and thus the ginsenoside Rh2 was used for wrinkle improvement. It was found to be difficult to commercialize.

From the above results, it can be seen that the collagen synthesis ability is remarkably excellent by introducing a hydroxyl group at the 25th carbon position of ginsenoside Rh2.

Preparation Example 1 Preparation of Cosmetic Formulation

1-1. Preparation of essence

Essence was prepared according to the content (parts by weight) described in Table 1 below using a ginsenoside Rh2 derivative.

Furtherance Content (parts by weight) Triethanolamine 0.25 Carboxy Vinyl Polymer 0.22 glycerin 4 Butylene glycol 2 Ginsenoside Rh2 Derivatives 1.5 Beeswax 0.5 Cetostearyl alcohol One Glyceryl Monostearate One Squalene 4 Purified water Quantity

1-2. Preparation of Soft Cosmetics

Softening longevity containing the ginsenoside Rh2 derivative as an active ingredient was prepared as shown in Table 2.

Raw material Content (parts by weight) 1,3-butylene glycol 1.00 Disodium ID 0.05 Allantoin 0.10 Dipotassium glycylizate 0.05 Citrix Acid 0.01 Sodium citrate 0.02 Glyceres-26 1.00 Arbutin 2.00 PEG-40
Hydrogenated Castor Oil 1.00 ethanol 30.00 Ginsenoside Rh2 Derivatives 0.5 coloring agent a very small amount Flavor a very small amount Purified water Remaining amount

1-3. Manufacture of nutritional cream

Nourishing cream containing ginsenoside Rh2 derivative as an active ingredient was prepared as shown in Table 3 below.

Raw material Content (parts by weight) 1,3-butylene glycol 7.0 glycerin 1.0 D-panthenol 0.1 Magnesium Aluminum Silicate 0.3 PEG-40 Stearate 1.2 Stearic acid 2.0 Polysorbate 60 1.5 Lipophilic glyceryl stearate 2.0 Sorbitan sesquioleate 1.5 Cetearyl Alcohol 3.0 Mineral oil 4.0 Squalene 3.8 Ginsenoside Rh2 Derivatives 1.5 vegetable oil 1.8 Dimethicone 0.4 Dipotassium glycylizate a very small amount Allantoin a very small amount Sodium hyaluronate a very small amount Tocopheryl Acetate Quantity Triethanolamine Quantity Flavor Quantity Purified water Remaining amount

1-4. Lotion

Lotions containing ginsenoside Rh2 derivatives as active ingredients were prepared as shown in Table 4 below.

Raw material Content (parts by weight) Cetostearyl alcohol 1.6 Stearic acid 1.4 Lipophilic Monostearic Acid Glycerin 1.8 PEG-100 Stearate 2.6 Sesquioleate Sorbate 0.6 Squalene 4.8 Macadamia oil 2 Jojoba oil 2 Tocopherol Acetate 0.4 Methylpolysiloxane 0.2 Tocopherol Acetate 0.4 1,3-butylene glycol 4 Xanthan Gum 0.1 glycerin 4 d-pandenol 0.15 Ginsenoside Rh2 Derivatives 1.0 Allantoin 0.1 Carbomer (2% aq.Sol) 4 Triethanolamine 0.15 ethanol 3 Purified water Quantity

Claims (9)

Ginsenoside Rh2 derivative represented by the following formula, or a cosmetic composition for improving wrinkles of the skin comprising a salt thereof.

(In the above formula, R is one selected from the group consisting of a hydroxyl group and a hydroxyalkyl group having 1 to 5 carbon atoms.) The method according to claim 1,
The ginsenoside Rh2 derivative is 25-hydroxy ginsenoside Rh2 (25-Hydroxy ginsenoside Rh2). The method according to claim 1,
The wrinkle improvement of the skin is a composition that is carried out by promoting the synthesis of collagen. Ginsenoside Rh2 derivative represented by the following formula, or a cosmetic composition for enhancing elasticity of the skin comprising a salt thereof.

(In the above formula, R is one selected from the group consisting of a hydroxyl group and a hydroxyalkyl group having 1 to 5 carbon atoms.) The method according to claim 4,
The ginsenoside Rh2 derivative is 25-hydroxy ginsenoside Rh2 (25-Hydroxy ginsenoside Rh2). The method according to claim 4,
The elasticity enhancement of the skin is to be carried out by promoting the synthesis of collagen. Ginsenoside Rh2 derivative represented by the following formula, or a cosmetic composition for skin regeneration comprising a salt thereof.

(In the above formula, R is one selected from the group consisting of a hydroxyl group and a hydroxyalkyl group having 1 to 5 carbon atoms.) The method according to claim 7,
The ginsenoside Rh2 derivative is 25-hydroxy ginsenoside Rh2 (25-Hydroxy ginsenoside Rh2). The method according to claim 7,
The skin regeneration is performed by promoting the synthesis of collagen.

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