KR101640736B1 - Composition for improving skin wrinkle - Google Patents

Abstract

The present invention relates to a composition for improving wrinkles containing a mixture of Paeoniflorin, Ginsenoside Re and Ferulic acid as an active ingredient. The mixture of the present invention not only promotes collagen synthesis but also inhibits collagenase activity, promotes hyaluronic acid production, is excellent in solubility and stability, and is thus very suitable for use as an active ingredient of a composition for improving wrinkles. Therefore, the composition of the present invention comprising the above mixture provides an excellent wrinkle-reducing effect. In addition, even when the above-mentioned effective ingredient is contained in a small amount, excellent efficacy is maintained. Therefore, it can be utilized as various formulations when applied to cosmetics, for example, and thus has an advantage that the range of application is wide.

Description

[Composition for improving skin wrinkle]

The present invention relates to a composition for improving wrinkles exhibiting excellent collagen synthesis promoting activity and collagenase inhibiting activity.

Collagen is a major substrate protein produced in fibroblasts of the skin and exists in extracellular epilepsy. Its important functions are mechanical rigidity of skin, resistance of connective tissues and binding force of tissues, support of cell adhesion, division of cells and differentiation Growth or wound healing) are known [van der Rest et al., 1990]. Such collagen is reduced by age and ultraviolet light irradiation, and is known to be closely related to the wrinkling of the skin [Arthur K. Balin et al., "Aging and the skin", 1989]. Also, in recent years, extensive research on skin aging has developed, and important functions of collagen in skin have been revealed.

In the prior art, there have been products that incorporate collagen into cosmetics from the skin moisturizing effect of collagen, but these cosmetics apply collagen to the skin surface, and since the collagen, which is a polymer, can not be expected to be moisturized by transdermal absorption, Can not be said.

On the other hand, there are known effective substances that promote collagen synthesis and exhibit wrinkle-reducing effects. For example, retinoic acid, transforming growth factor (TGF) [Cardinale G. et al, Adv. Enzymol., 41, p. 425, 1974], animal-derived placenta-derived proteins [Japanese Patent Application No. 8-231370], betulinic acid [Japanese Patent Application No. 8-208424], chlorella extract [Japanese Patent Application No. 9-40523, 36283] is known as a collagen synthesis promoting substance. However, the above-mentioned effective ingredients are limited in the use amount due to safety problems such as irritation and redness when applied to the skin, or have insufficient effect, so that the effect of improving the skin function by promoting the collagen synthesis of the skin can not be expected. Therefore, there is a desperate need to develop a wrinkle-improving active ingredient that is safe for living body, stable in its effective component, and most effective than the existing collagen synthesis promoting substance.

In addition, hyaluronic acid is a type of glucose aminoglycan (nonsulfated glycosaminoglycan) synthesized in a fibroblast and other plasma membrane of skin cells. It is composed of 200 to 10,000 repeating di Is a linear polymeric polysaccharide substance having a size of 1 × 10 ⁵ to 5 × 10 ⁶ Da in which glucaconic acid and N-acetylglucosamine residues, which are disaccharide units, are repeatedly connected in a chain. In particular, skin is known to contain more than 50% of hyaluronic acid in the body, and hyaluronic acid is a major constituent of the extracellular matrix and is involved in the storage and diffusion of moisture retention, intercellular spacing, cell growth factors and nutrients But also to the division, differentiation and migration of cells.

It has been reported that the synthesis of hyaluronic acid in skin cell cultures is increased by various kinds of growth factors, transretinoin acid, N-methyl serine, etc. [ Biochem . J. 258, 919-922; Biochem. J. 283, 165-170; Biochem . J. 307, 817-821; J. Biol . Chem . 272, 4787-4794; J Invest Dermatol 92, 326-332; Biol Pharm Bull 17, 361-364; And Skin Pharmacol Appl Skin Physiol 12, 276-283] and estradiol and its analogues applied to the skin increase the synthesis of hyaluronic acid [ Steroids 16, 1-3; J Invest Dermatol 87, 668-673; And Skin Pharmacol Appl Skin Physiol 15, 175-183], but the detailed mechanism of hyaluronic acid metabolism has not yet been elucidated. It is known that the synthesis of hyaluronic acid proceeds by the hyaluronic acid synthase (HAS) on the inner surface of the cell membrane and accumulates in the extracellular matrix through the cell membrane during synthesis [ J. Biol . Chem . 272, 13997-14000).

Three types of hyaluronan synthase genes in mammals have been reported, HAS1, HAS2 and HAS3, which are highly similar in sequence. In this regard, it has been reported that the expression of HAS2 gene is increased when epidermal growth factor (EGF) is added to the epidermal cell culture fluid [ J. Biol . Chem . 276,20428-20435]. However, studies on the distribution of hyaluronic acid in cells and tissues, various factors related to hyaluronic acid, and enzymes such as hyaluronic acid synthase or factors regulating hyaluronic acid activity are very inadequate.

As described above, it has been reported that more than 50% of the hyaluronic acid present in the mammalian body is distributed in the skin, especially the epidermal intercellular space and the connective tissue of the dermis. Such hyaluronic acid is mainly synthesized by keratinocytes and fibroblasts . The amount of hyaluronic acid in human skin has been reported to decrease with aging, and the reduction of hyaluronic acid in the skin is considered to be one of the direct causes of decreased skin elasticity and moisture content due to aging [ Biochem Biophys Acta 279, 265-275; Carbohydr Res 159, 127-136; And Int J Dermatol 33, 119-122).

Therefore, attention has been paid to the possibility of skin application of hyaluronic acid as described above, and research on a method capable of effectively producing or injecting hyaluronic acid or increasing the production of hyaluronic acid in the human body has been actively carried out. However, Is not yet known.

SUMMARY OF THE INVENTION The present invention has been made in view of the problems of the prior art described above, and it is an object of the present invention to provide a pharmaceutical composition which exhibits excellent collagen synthesis promoting activity, collagenase inhibiting activity and hyaluronic acid producing effect, To provide a composition for promoting collagen formation that can be applied in various formulations, thereby providing a composition for improving wrinkles.

In order to achieve the above object, the present invention features a composition for improving wrinkles comprising a mixture of Paeoniflorin, Ginsenoside Re, and Ferulic acid as an active ingredient.

The present invention relates to a composition for improving wrinkles containing a mixture of corniflorin, ginsenoside Re and ferulic acid as an active ingredient. In particular, the present invention relates to a composition for improving wrinkles, which has no adverse effects on the skin, promotes collagen synthesis and hyaluronic acid production, Since it inhibits collagenase, it can be used effectively for improving wrinkles.

The composition of the present invention has an advantage of promoting excellent collagen formation promoting ability, collagenase inhibitory ability and hyaluronic acid production, especially when the effect is contained in a small amount. Accordingly, the composition of the present invention is excellent in the ability to suppress and improve wrinkles associated with reduction in collagen and lowering of elasticity, and has excellent healing efficacy against wounds generated in skin and the like. In addition, even when the above-mentioned effective ingredient is contained in a small amount, excellent efficacy is maintained. Therefore, it can be utilized as various formulations when applied to cosmetics, for example, and thus has an advantage that the range of application is wide.

Hereinafter, the composition for improving wrinkles of the present invention will be described in more detail as follows.

The composition for improving wrinkles of the present invention contains a mixture of lanoflourin, ginsenoside Re and ferulic acid as an active ingredient. These compounds are excellent for promoting collagen and collagenase inhibitory activity and hyaluronic acid synthesis (enhancing expression of HAS2 mRNA) of skin fibroblasts while being safe in vivo. Excellent wrinkle-improving effect.

These compounds can be chemically synthesized through various organic chemistry methods known in the art and can be easily obtained from plants and the like.

Paoniflorin is a peony ( Paeonia ) lactiflora (peony and Paeonlaceae), peony and plant roots, and ginsenoside Re is found in ginseng Panax ginseng CA Meyer (Acanthaceae and Araliaceae), and Peruvian mountains are found in the Cnidium (川芎) Cnidium Many species are present in plants and plants such as officinale (mountain and Umbellifere), and the method of extracting each component from this is not particularly limited, and various extraction methods known in the art can be applied without limitation.

The composition of the present invention includes a lanofluorine, wherein the lanofluorine is preferably a compound represented by the following formula (1). Prior art studies have confirmed that lanofluorin has an effective effect on skin wrinkles [Korean Patent Application No. 2005-0035482].

[Chemical Formula 1]

An example of the production of the onion flourine used in the present invention will be described in detail as follows. When the roots of the peony are said three times, the peony is extracted and mixed three times with 3 times each time with 5 times of 75% ethanol. Residual ethanol in the concentrate is volatilized and water is added in one part of the residue to dissolve by heating to make a suspension. This suspension is fractionated three times with the same amount of ethyl ether, and the suspension is separated and layered. The concentrated fraction is added to a 200-300 mesh silica gel column, and the fluidized phase is separated into chloroform: acetone (4: 1), concentrated and dried to prepare powder.

Meanwhile, the composition of the present invention includes ginsenoside Re, wherein the ginsenoside Re is preferably a compound represented by the following formula (2). The above-mentioned ginsenoside Re is also excellent in biostability and promoting collagen synthesis. In addition, since ginsenoside Re exhibits an effect of inhibiting collagenase activity, which is a collagenolytic enzyme, it is included in the present invention to improve the ability of the composition to promote collagen formation. For example, When used, the effect of improving the wrinkles of the skin is enhanced, thereby improving the elasticity of the skin.

(2)

Such ginsenoside Re can be chemically synthesized through various organic chemistry methods and the like known in the art, and can be easily obtained from plants such as flangenidine. The ginsenoside Re is particularly present in ginseng or red ginseng. The method of extracting the desired compound from the ginseng or red ginseng is not particularly limited, and various extraction methods known in the art can be applied without limitation. Examples of such methods include finely cutting ginseng and the like and adding it to water, a solvent containing anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms, ethyl acetate, acetone and / or chloroform, heating and extracting the solvent fraction, . ≪ / RTI >

The composition of the present invention may further comprise a ferric acid, wherein the ferulic acid is preferably a compound represented by the following formula (3). Ferulic acid is a precursor of lignin that forms plant cell walls. Ferulic acid has an antioxidant activity that neutralizes active oxygen such as superoxide anion, nitric oxide, and hydroxyl radical, The effect is known to be superoxide dismutase (SOD), which protects living organisms from the toxicity of active oxygen. In particular, the cell has an excellent inhibitory effect on lipid oxidation. Therefore, it is known to be effective for anti-aging due to such an effect, and antioxidant power is very strong, and it has a very good effect of removing melanin pigment and inhibiting spots and freckles, and thus has a good effect on blood sugar and lowering of cholesterol have. In particular, as shown in the following examples, the effect of improving skin wrinkles is excellent, so that when mixed with ferulic acid, the effect of the present invention is enhanced and the elasticity of the skin is enhanced.

(3)

In the present invention, "wrinkle improvement" refers to inhibiting or inhibiting the generation of wrinkles on the skin, or alleviating the wrinkles already generated.

The wrinkle-improving composition of the present invention preferably contains a mixture of Paeoniflorin, ginsenoside Re and ferulic acid in an amount of 1 × 10 ^-5 to 10 wt%, more preferably 1 × 10 ^-5 to 5 By weight, more preferably in an amount of 0.1% by weight. If the content is less than 1 x 10 < ^-5 > wt%, the effect of promoting collagen production and collagenase inhibition and hyaluronic acid synthesis (HAS2 mRNA expression enhancement) If the amount is more than 10% by weight, the overall processability of the composition such as solubility in a solvent will be lowered, and the use of the composition for various purposes such as cosmetic formulations to be described later may be restricted.

In addition, in the present invention, the synergy effect can be confirmed by mixing the above-mentioned lanofluorine, ginsenoside Re, and ferulic acid in a specific ratio. It is preferable that the optimum blending ratio is in the weight ratio of corniflorin: ginsenoside Re: ferulic acid 1: 3: 1 to 3: 8: 4. When the content of ferulic acid in the weight ratio is less than 40%, the function of ferulic acid which assists in absorption of valine florin and ginsenoside Re is weakened, and there is a possibility that the effect of wrinkle improvement when applied to skin is lowered. The effect is low.

In the composition for accelerating collagen formation of the present invention, the additives other than the above-mentioned effective ingredients are not particularly limited, and those commonly used in this field can be used without limitation. For example, when the composition is used for medical purposes, a pharmaceutically acceptable carrier may be included. When it is applied to cosmetics, conventional additives commonly used in cosmetics may be used without limitation.

The wrinkle-improving composition of the present invention may further include a known wrinkle-improving ingredient in addition to the above-mentioned effective ingredient. The wrinkle-improving effect of the composition of the present invention may be further enhanced by including an additional wrinkle-improving ingredient. When the wrinkle-improving ingredient is added, skin safety, easiness of formulation, and stability of effective ingredients can be taken into consideration in combination use. In one embodiment of the present invention, the wrinkle-improving composition is a wrinkle-improving ingredient known in the art and includes one or more selected from the group consisting of retinoic acid, TGF, protein from animal placenta, betulinic acid and chlorella extract, And may further include at least two kinds of wrinkle improving ingredients. The additional wrinkle improving ingredient may be contained in an amount of 0.0001% by weight to 10% by weight based on the total weight of the composition. The content of the wrinkle improving ingredient may be selected from the group consisting of collagen synthesis promoting or collagenase inhibiting activity, skin safety, Lt; / RTI >

In the present invention, the composition for improving wrinkles may be a pharmaceutical composition or a cosmetic composition. When formulating the composition for improving wrinkles into a medicament or a cosmetic composition, it may contain known pharmaceutically acceptable excipients which act as carriers for the active ingredient. When formulated as a medicament, the contents disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA can be referred to. When formulating into cosmetics, International cosmetic ingredient dictionary, 6th ed., The cosmetic, Toiletry and Fragrance Association , Inc., Washington, 1995, which is incorporated herein by reference in its entirety. Which are incorporated herein by reference.

When the composition for improving wrinkles of the present invention is a cosmetic composition, the composition may include, but is not limited to, emulsions such as lotion, facial lotion, body lotion, Makeup remover, cleansing foam, soap such as foundation, powder, cleansing lotion, cleansing oil such as cream, essence, cosmetic lotion, spray, gel, pack, sunscreen, makeup base, liquid type, solid type or spray type , A body wash, and the like. In this case, the cosmetic composition may contain at least one selected from the group consisting of a surfactant, an emulsifier, a soap acid, a solvent, a binder, a diluent, a lubricant, a stabilizer, an antioxidant, a water, a lower alcohol, a thickener, a chelating agent, Antioxidants, antifungal agents, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, flocculants, humectants, fragrances, fragrance carriers, preservatives, proteins, silicones, solubilizers, sugar derivatives, sunscreens, vitamins , Plant extracts, and waxes. The pharmaceutical composition of the present invention may contain one or more pharmacologically acceptable excipients.

Advantages and features of the present invention and methods of achieving them will become apparent with reference to the embodiments described in detail below. However, it is to be understood that the present invention is not limited to the disclosed embodiments, but may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, To fully disclose the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims.

Example  One: Collagenase  Identification of the activity inhibition effect

Paoniflorin, Ginsenoside Re, Perucic acid (Fluka, Japan, Cat. No. 46280, 98% or more], and each of these mixtures, the inhibitory effect on collagenase activity was confirmed as follows.

In order to observe the collagen-decomposing enzyme activity inhibitory effect, which is a commercially available substrate, Dabcyl-r-Abu-Pro- GLu-Gly-Leu-Glu (EDANS) -Ala-Lys-NH collagenase I decompose the Gly-Leu bond ₂ , The N-terminus of the Dabcyl group and the C-terminus of the EDNAS are experiments using a quencher-acting mechanism.

Each of the lysophospholipid, ginsenoside Re, ferulic acid, and the mixture was added to a 96-well plate in a 96-well plate, and the mixture was reacted at 37 ° C for 1 hour with a reaction buffer and a commercially available substrate. The reaction was terminated by adding 5 ul of EDTA. At this time, the degree of color development was measured by measuring the absorbance at 340 nm / 520 nm using a flurometer [Bob Beekman et al., FEBS, 390, 221-225, 1996]. As a negative control group, a group without the compound was used, and a positive control group containing 1% of retinoic acid was used.

The inhibition rate of collagenase activity was calculated by the following formula (1), and the results are shown in Table 1 below.

[Equation 1]

[Table 1]

As can be seen from the above Table 1, inhibition of collagenase activity of a mixture of a mixture of lanofluopine, ginsenoside Re and ferulic acid at a specific ratio (weight ratio of 1: 3: 1 to 3: 8: 4) And the effect was remarkably excellent.

Example  2: Confirmation of promoting collagen synthesis

The effect of promoting collagen synthesis at the cellular level was examined by adding each of corniflorin, gonenoside Re, ferulic acid, and the mixture thereof to a culture solution of human-derived fibroblasts.

The synthesized collagen was quantitated using a PICP EIA kit (Procollagen Type I C-Peptide Enzyme Immunoassay Kit).

In the experiment, the final concentration of each sample was 1 / / ml and 10 / / ml, and the mixing ratios of the respective samples are shown in Table 1 below. Each sample was added to the culture medium of human fibroblasts and cultured for 1 day. Then, the culture solution was taken and the degree of collagen synthesis at each concentration was measured at 450 nm using a spectrophotometer with a PICP EIA kit. For the comparison of the effects, the degree of collagen synthesis was measured by the same method for the culture medium of fibroblasts (control group) to which nothing had been added and the sample added with vitamin C to a final concentration of 52.8 / / ml. The amount of collagen production was measured as the UV absorbance, and the increase rate of collagen production was calculated as a ratio of collagen production relative to the control. The results are summarized in Table 2 below.

[Table 2]

As can be seen from the results in Table 2 above, when the combination of lioniflurin, ginsenoside Re, and ferulic acid is used, the effect of collagen synthesis, which is lower than that of vitamin C, . It was also confirmed that a remarkable synergistic effect was exhibited when the above-mentioned addition was simultaneously performed, as compared with the case where each of lanofluorin, ginsenoside Re and ferulic acid was added singly.

Example  3: Mouse Derived fibroblast NIH  3 T3 In HAS2  Assessment of increased expression

Mouse fibroblast NIH 3T3 was cultured in DMEM medium containing 10% fetal bovine serum for 24 hours. The cultured cells were washed twice with DMEM medium containing no bovine serum, and then treated with the same medium for 12 hours to remove the effect of bovine serum. The culture medium of the thus cultured cells was again added to each DMEM medium containing lanophospholines, ginsenoside Re, ferulic acid and a mixture thereof at a concentration of 1 μg / ml or 10 μg / ml, Replaced and treated for 12 hours. After 12 hours, the cells were collected, washed with cold phosphate buffer (PBS), and 1 ml of RNA isolation kit (Tri-reagent, Gibco BRL) was added to extract total RNA. Quantitative reverse transcription PCR was performed by the following method Respectively. The sense primer for the PCR of hyaluronic acid synthetase 2 (HAS2) and GAPDH was 5'-CTGTGAAAAGGCTGACCTAC-3 '(SEQ ID NO: 1) and the anti-sense primer was 5'-TCAGTAAGGCACTTGGACCG-3' (SEQ ID NO: 2) .

One gram of total RNA was reverse-transcribed using reverse transcription system (Promega, USA) to obtain cDNA. 2 μl of the reverse transcription reaction solution was mixed with 50 μl of PCR reaction buffer of 50 mM KCl, 10 mM tris-HCl (pH 8.3), 5 mM MgCl ₂ and 0.16 mM dNTP, and 20 pmol of primer and 1.25 U of Taq DNA polymerase 30 cycles of 94 ° C for 60 seconds, 60 ° C for 120 seconds, and 72 ° C for 120 seconds were performed. PCR products were electrophoresed on agarose gel and analyzed with Fluoro-S MultiImager (BioRad).

The results of the analysis are summarized in Table 3 below. Table 3 shows the expression level (HAS2 mRNA level) of the HAS2 gene according to the concentration when the respective extract samples were treated at a concentration of 1 μg / ml or 10 μg / ml as a relative value (%) to the control group . GAPDH is a gene that is used as an internal control gene to confirm gene expression changes by quantitative reverse transcription PCR, and can be standardized by indicating the relative amount of a specific gene, here HAS2, to the change of GAPDH . As shown in the following Table 3, the results showed that the expression of hyaluronic acid synthase 2 was increased at a concentration of 1 μg / ml and 10 μg / ml, respectively, with lanoflorin, ginsenoside Re, ferulic acid and mixtures thereof And at the dose of 1 μg / ml, periulic acid and ginsenoside Re and lonifurin were effective in the order of 10 μg / ml, and 1 μg / ml and 10 μg / ml Mixed samples were most effective at both concentrations.

[Table 3]

Example  4: Wrinkle improvement effect evaluation

A 6-week-old hairless mouse was used to test the wrinkle-reducing effect of each of the wrinkles induced by light in the case of the corniflorin, ginsenoside Re, ferulic acid and the mixture thereof.

Each of corniflorin, ginsenoside Re, ferulic acid and a mixture thereof was dissolved in 1,3-butylene glycol at 0.5%, and the test method was as follows.

Was dissolved in 1,3-butylene glycol at a concentration of 5 mg / ml and adjusted so that the concentrations of lanofinoline, ginsenoside Re, ferulic acid and their mixture were 0.5 mg / ml and 4.5 mg / ml, respectively Respectively. Specifically, mouse wrinkles were formed by irradiating the mice with 2 MED for 3 weeks each week for 10 weeks using a solar simulator, and a control group treated with 1,3-butylene glycol to which no sample was added And 5 mg / ml of sample solution were treated with 0.5 ml / ㎠ (2.5 mg / ㎠) twice a day for 6 weeks. The degree of wrinkle improvement was judged by visual inspection through visual observation and photographing, and the evaluation criteria were three stages of no improvement, little improvement, and considerable improvement compared with those before the sample treatment in the sample treatment group and the control group Are shown in Table 4 below.

[Table 4]

Manufacturing example  1 and Comparative Example  1: Manufacture of external ointment for skin

Skin external ointment containing a mixture (3: 2: 5) of corniflorin, ginsenoside Re and ferulic acid as an active ingredient was prepared according to a conventional method, as shown in the following Table 5. In addition, the ointment for external use for skin prepared from the other ingredients except for the active ingredient was prepared in Comparative Example 1.

[Table 5]

Manufacturing example  2 and Comparative Example  2: Preparation of essence

A skin aging-preventing and wrinkle-improving cosmetic essence formulation containing a mixture (3: 2: 5) of corniflorin, gonenoside Re and ferulic acid as an active ingredient was formulated in Preparation Example 2, except that it contained no active ingredient And the cosmetic essence was prepared in the same manner as in Preparation Example 2, The detailed composition is shown in Table 6 below.

[Table 6]

Example  5: Confirm skin wrinkle improvement effect through panel test

For the essences of Preparation Example 2 and Comparative Example 2, the skin wrinkle-reducing effect was tested as follows for healthy 35- to 50-year-old women.

30 women aged 35 to 50 years were divided into two groups by 15 persons, Group 1 was the essence of Preparation Example 2 containing 0.3% of laurylphosphine, ginsenoside Re and ferulic acid, 2 was applied to the facial area once a day for 3 months. After 3 months, improvement of skin wrinkles was evaluated by image analysis of questionnaires and skin wrinkles. The subjects' questionnaires were judged to have no improvement, little improvement, and considerable improvement as compared with before use in terms of improvement in skin wrinkles and elasticity, and the results are shown in Table 7 below.

[Table 7]

As shown in Table 6, when the essence of Preparation Example 2 containing 0.3% of a mixture of corniflorin, ginsenoside Re and ferulic acid was used, the effect of improving skin wrinkles .

<110> LG HOUSEHOLD & HEALTH CARE LTD. <120> Composition for improving skin wrinkle <160> 2 <170> Kopatentin 1.71 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer <400> 1 ctgtgaaaag gctgacctac 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer <400> 2 tcagtaaggc acttggaccg 20

Claims (8)

A composition for improving wrinkles, comprising a mixture of corniflorin, gonenoside Re and ferulic acid as an active ingredient.
The wrinkle-improving composition according to claim 1, wherein the mixture is a mixture of lauinflorin, ginsenoside Re and ferulic acid at a weight ratio of 1: 3: 1 to 3: 8: 4.
The wrinkle-improving composition according to claim 1, wherein the active ingredient is contained in an amount of 1 × 10 ^-5 to 10% by weight based on the total weight of the composition.
The method of claim 1, further comprising adding one or more kinds of wrinkle improving ingredients selected from the group consisting of retinoic acid, transforming growth factor (TGF), animal placenta-derived protein, betulinic acid and chlorella extract By weight.
The wrinkle-improving composition according to claim 4, wherein the wrinkle-improving component comprises 0.0001 to 10% by weight based on the total weight of the composition.
The composition according to claim 1, wherein the composition is at least one selected from the group consisting of lotion, milky lotion, cream, essence, cosmetic lotion, spray, gel, pack, sunscreen, makeup base, foundation, powder, Wherein the wrinkle-improving composition comprises:
The composition according to claim 1, wherein a pharmacologically acceptable excipient is added in addition to the active ingredient.
8. The composition of claim 7, wherein the pharmacologically acceptable excipient is selected from the group consisting of a surfactant, an emulsifier, a soap acid, a solvent, a binder, a diluent, a lubricant, a stabilizer, an antioxidant, water, a lower alcohol, a thickener, Preservatives, antibiotics, antioxidants, antifoaming agents, antimicrobial agents, antifungal agents, enzymes, plant or mineral oils, fats, fluorescent substances, fungicides, flocculants, humectants, fragrances, fragrance carriers, preservatives, , Sugar derivatives, sunscreen agents, vitamins, plant extracts, and waxes.