Composition for improving skin wrinkles, skin texture or whitening, comprising a retinoid and a retinoid booster

Abstract

The present invention relates to a composition containing a retinoid and a material for enhancing the efficacy of the retinoid, i.e., a retinoid booster, and having an increased efficacy of the retinoid. The composition for improving skin wrinkles of the present invention can significantly improve the skin wrinkle-improving effect of the retinoid by suppressing the mechanism by which CYP enzymes oxidatively decompose retinoic acid by a specific retinoid booster compound.

Description

Technical Field

[0001] The present invention relates to a composition containing a retinoid and a material for enhancing the efficacy of the retinoid, i.e., a retinoid booster, and having an increased efficacy of the retinoid.

[0002] This application claims priority based on Korean Patent Application No. 10-2022-0076126 filed on June 22, 2022, and all of the content disclosed in the specification and drawings of the said application is incorporated into this application.

Background Art

[0003] With the increase in the elderly population and the rise in life expectancy, the interest in preventing skin aging, which emphasizes improving skin wrinkles, is increasing more and more. Skin is an organ that occupies about 16% of the human body volume, exists on the outermost part of the body, and protects the body from the external environment and stimuli. Such skin is always exposed compared to internal organs in the body, so it is easily attacked by external stimuli. In particular, in the case of facial skin, since it is directly exposed to ultraviolet rays and pollutants, it is more likely to age compared to the skin of other parts.

[0004] Skin aging is divided into endogenous aging that occurs naturally and exogenous aging caused by external factors. The main factors of endogenous aging include genetic factors, which determine the structure and changes of skin cells and tissues. On the other hand, the factors of exogenous aging are those derived from the outside, such as nutritional deficiency, ultraviolet rays, and the influence of environmental pollution. Different from genetic factors, these are factors that can be prevented and avoided as much as possible.

[0005] Due to such factors, the progression of skin aging leads to skin dryness, roughness, wrinkle formation, loss of elasticity, pigmentation, and other symptoms. In particular, in the case of wrinkles and loss of elasticity, which are typical skin aging symptoms, it is known that the decrease and deformation of collagen and elastin, the main proteins in the dermis, are directly involved. That is, the onset of skin wrinkles starts from the aging of the dermis. As the structure of elastin, an elastic fiber, changes, the skin sags and wrinkles can form. Research has been reported that wrinkles increase due to the inhibition of collagen synthesis by the increased activity of MMP (matrix metalloproteinase), which decomposes connective tissue components including collagen in the dermis.

[0006] Retinoids (including retinol, retinal, retinoic acid, retinoid derivatives, etc.) have been proven to improve skin wrinkles by increasing the thickness of the epidermis, strengthening the ECM layer of the dermis, and increasing collagen by reducing collagen-degrading enzyme (MMP-1). The retinoic acid is a prescription drug, and the retinol or retinoid derivatives are widely used for wrinkle improvement in cosmetics and the like.

[0007] Regarding the mechanism of action of the retinoids in the skin, first, retinol and retinal can be mutually converted by retinol dehydrogenase. The retinal is oxidized by retinol dehydrogenase to be converted into retinoic acid. The retinoic acid can move into the nucleus, bind to the retinoic acid receptor, activate it, and express downstream genes, thereby exerting the effect of improving skin wrinkles.

[0008] However, it is known that CYP enzymes (cytochrome P450) such as CYP26 expressed in keratinocytes oxidize and decompose retinoic acid. That is, by suppressing the oxidation reaction of retinoic acid by the CYP enzymes, it is possible to increase the efficacy of improving skin wrinkles by retinoic acid.

[0009] Research is underway due to the need for ingredients and technologies that can maximize the effects when mixed with retinoids. In Patent Document 1, a "stable skin care composition containing a retinoid and a retinoid booster system" is disclosed. However, in order to increase the anti-wrinkle effect of retinoic acid on the skin, almost nothing is known in the technical field to which the present invention belongs about new compounds that can suppress the action of the CYP enzyme system. Therefore, it is necessary to discover such new compounds.

Prior Art Documents

Patent Documents

[0010]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0011] An object of the present invention is to provide a composition capable of increasing the anti-wrinkle improvement effect of retinoids by preventing retinoic acid from being oxidized and decomposed by CYP enzyme system in skin cells when retinoids are applied to the skin.

[0012] Another object of the present invention is to provide a composition capable of improving the texture of the skin by promoting desquamation of keratin and improving epidermal tissue of retinoids, or increasing the whitening effect by promoting the skin turnover of retinoids.

Means for Solving the Problems

[0013] As a result of intensive research to discover novel compounds capable of enhancing the skin wrinkle-improving effect of retinoids, the present inventors surprisingly found that a specific retinoid booster compound of the present invention suppresses CYP enzymes that oxidatively decompose retinoic acid, thereby increasing the bioavailability of retinoic acid and enhancing the skin wrinkle-improving effect. Accordingly, the present inventors confirmed that when a specific retinoid booster compound is combined with a retinoid and applied to crow's feet, under-eye wrinkles, or nasolabial folds, a remarkable synergistic effect occurs in improving skin wrinkles as compared to treatment with the retinoid alone, leading to the present invention.

[0014] The present invention provides a cosmetic composition for improving skin wrinkles, comprising a retinoid and at least one retinoid booster selected from the group consisting of prolinamidoethyl imidazole, apigenin, luteolin, and the like.

[0015] The present inventors confirmed by analysis of cell metabolites that prolinamidoethyl imidazole, apigenin, or luteolin suppresses the decomposition of retinoic acid, and confirmed that these can function as retinoid boosters (Experimental Examples 1 and 2). Further, the present invention has found that the retinoid booster compound significantly suppresses the gene expression of CYP enzymes, thereby confirming suppression of the decomposition of retinoic acid by CYP enzymes (Experimental Example 3). In addition, the present inventors have confirmed that the combination of retinoic acid and a retinoid booster strengthens the thickness of the epidermis (Experimental Example 4) and also increases the expression level of collagen mRNA (Experimental Example 5). Further, when the combination of retinoic acid and a retinoid booster was actually applied to the skin, it was confirmed that a remarkable wrinkle-improving effect appeared (Experimental Example 6). As described above, prolinamidoethyl imidazole, apigenin, or luteolin can significantly increase the skin wrinkle-improving effect of retinoic acid by suppressing the oxidative decomposition of retinoic acid converted from a retinoid by suppressing CYP enzymes.

[0016] In one aspect of the present invention, the retinoid means a compound having the skeleton of vitamin A (retinol), and may include retinol, retinal, retinoic acid, or retinoid derivatives. The retinoic acid may include tretinoin (all-trans-retinoic acid), isotretinoin (13-cis-retinoic acid), or alitretinoin (9-cis-retinoic acid). The retinoid derivatives may include retinyl palmitate, retinyl acetate, etretinate, acitretin, adapalene, bexarotene, tazarotene, or polyethoxylated retinamide.

[0017] In one aspect of the present invention, the retinoid may be contained in an amount of 0.001 to 1% by weight, preferably 0.005 to 0.8% by weight, more preferably 0.01 to 0.5% by weight, and most preferably 0.02 to 0.3% by weight based on the total weight of the composition. Since the retinoid may cause skin irritation when applied to the skin, there is a limit to its appropriate dosage. However, in the present invention, by combining a retinoid booster with the retinoid so that the retinoid is not contained in excess, the effect of improving skin wrinkles can be significantly increased without skin irritation. When the retinoid is contained in an amount exceeding 1% by weight based on the total weight of the composition, there is a risk of causing skin irritation, and when it is less than 0.001% by weight, the effect of improving skin wrinkles may not be fully exerted.

[0018] In one aspect of the present invention, the retinoid booster may be contained in an amount of 0.00001 to 2% by weight, preferably 0.001 to 1.5% by weight, more preferably 0.05 to 1% by weight, based on the total weight of the composition. When the retinoid booster is contained in an amount of less than 0.00001% by weight based on the total weight of the composition, the boosting effect of the retinoid efficacy may not be fully exerted, and when it is contained in an amount exceeding 2% by weight, skin irritation may be induced.

[0019] In one aspect of the present invention, the weight ratio of the retinoid to the retinoid booster may be 1:3 to 1,000, preferably 1:4 to 950, more preferably 1:5 to 900 (retinoid:retinoid booster). When the weight ratio of the two components is within the above range, the inhibitory effect of the retinoid booster on retinoic acid decomposition increases, and the skin wrinkle improvement effect can be significantly enhanced.

[0020] In one aspect of the present invention, when the retinoid booster is apigenin, the weight ratio of the retinoid to the retinoid booster may be 1:3 to 50, preferably 1:4 to 35, more preferably 1:5 to 20. When the retinoid booster is luteolin, the weight ratio of the retinoid to the retinoid booster may be 1:3 to 60, preferably 1:4 to 50, more preferably 1:5 to 40. When the retinoid booster is proline amide ethyl imidazole, the weight ratio of the retinoid to the retinoid booster may be 1:40 to 1,000, preferably 1:50 to 950, more preferably 1:55 to 900. Apigenin and luteolin suppress the gene expression of CYP family enzymes, and proline amide ethyl imidazole directly acts on CYP family enzymes to suppress the decomposition of retinoic acid. Due to the action mechanism of each such retinoid booster, when it is within the above weight ratio range, the effect of increasing the retinoid efficacy is excellently exerted.

[0021] In one aspect of the present invention, the cosmetic composition for improving skin wrinkles can be manufactured into a dosage form selected from the group including, but not limited to, solutions, topical ointments, creams, foams, nutritive lotions, emollient lotions, packs, softeners, emulsions, makeup bases, essences, liquid detergents, bath salts, sunscreen creams, sun oils, suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansings, oils, powder foundations, emulsion foundations, wax foundations, patches, and sprays.

[0022] In one aspect of the present invention, the cosmetic composition for improving skin wrinkles may further contain one or more substances selected from the group consisting of oil, water, surfactants, humectants, alcohols, thickeners, chelating agents, pigments, preservatives, and fragrances, but is not limited thereto. Further, the cosmetic composition of the present invention may contain a cosmetically acceptable carrier.

[0023] In one aspect of the present invention, when the dosage form of the cosmetic composition for improving skin wrinkles is an ointment, paste, cream or gel, animal oils, vegetable oils, waxes, paraffin, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silica, talc, zinc oxide, or mixtures thereof may be used as the carrier component.

[0024] In one aspect of the present invention, when the dosage form of the cosmetic composition for improving skin wrinkles is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate, polyamide powder, or mixtures thereof may be used as the carrier component. In particular, in the case of a spray, it may further contain a propellant such as chlorofluorohydrocarbon, propane / butane, or dimethyl ether.

[0025] In one aspect of the present invention, when the dosage form of the cosmetic composition for improving skin wrinkles is a solution or an emulsion, as the carrier component, a solvent, a solubilizer, an emulsifier, or the like can be used. For example, water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, or 1,3-butyl glycol oil, or the like can be used. Further, as the carrier component, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil, sesame oil, glycerol fatty acid ester, polyethylene glycol, or fatty acid ester of sorbitan, or the like can be used.

[0026] In one aspect of the present invention, when the dosage form of the cosmetic composition for improving skin wrinkles is a suspension, as the carrier component, a liquid diluent such as water, ethanol, or propylene glycol, a suspension such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum hydroxide, bentonite, agar, or tragacanth, or the like can be used.

[0027] In one aspect of the present invention, when the dosage form of the cosmetic composition for improving skin wrinkles is a capsule, it can be formulated into forms such as alginate capsules, agar capsules, gelatin capsules, wax capsules, or double capsules, but is not limited thereto.

[0028] In one aspect of the present invention, the cosmetic composition for improving skin wrinkles, in addition to retinoids and retinoid boosters, may contain commonly used adjuvants, for example, hydrophilic or lipophilic gelling agents, hydrophilic or oleophilic active agents, preservatives, antioxidants, solvents, fragrances, fillers, blockers, pigments, deodorants, or dyes, or the like.

[0029] In addition, the present invention provides a cosmetic composition for skin whitening or improving skin texture, comprising a retinoid and at least one retinoid booster selected from the group including proline amide ethyl imidazole, apigenin, luteolin, and the like.

[0030] In addition, the present invention provides a pharmaceutical composition for improving skin wrinkles, comprising a retinoid and at least one retinoid booster selected from the group including proline amide ethyl imidazole, apigenin, luteolin, and the like. In the pharmaceutical composition, the effective amounts of the retinoid and the retinoid booster may vary depending on the form in which the pharmaceutical composition is commercialized, the method of applying the retinoid and the retinoid booster to the skin, and the time staying on the skin. The pharmaceutical composition may be in various dosage forms for oral or parenteral administration. In formulating, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, and the like that are commonly used may be used. Solid preparations for oral administration include purified products, pills, powders, granules, capsules, and the like. Such solid preparations are prepared by mixing at least one excipient, for example, starch, calcium carbonate, sucrose, lactose, or gelatin, with one or more compounds. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral administration include suspensions, oral solutions, emulsions, syrups, and the like. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, preservatives, and the like may be included. Preparations for parenteral administration may include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions. As non-aqueous solvents and suspensions, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used.

[0031] The present invention also provides a food composition for improving skin wrinkles, which comprises a retinoid and at least one retinoid booster selected from the group including proline amide ethyl imidazole, apigenin, luteolin and the like. The food composition may contain, in addition to the retinoid and the retinoid booster, a food additive acceptable in food science. The food additive means a component that can be added to food supplementarily and can be appropriately selected and used by those skilled in the art. Examples of food additives include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohol or carbonating agents used in carbonated beverages and the like.

[0032] The present invention also provides a quasi-drug composition for improving skin wrinkles, which comprises a retinoid and at least one retinoid booster selected from the group including proline amide ethyl imidazole, apigenin, luteolin and the like. The quasi-drug composition may further contain a pharmaceutically acceptable carrier, excipient or diluent as necessary in addition to the above components. The pharmaceutically acceptable carrier, excipient or diluent is not limited as long as it does not inhibit the effects of the present invention. For example, it may include fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, fragrances, preservatives and the like. Examples of the quasi-drug composition include, but are not limited to, disinfectants, shower foams, ointments, wet tissues, coating agents and the like. The formulation method, volume, usage method, components and the like of the quasi-drug can be appropriately selected from the known ordinary techniques in the technical field.

[0033] The present invention also provides a method for improving skin wrinkles, which includes administering to an individual a composition for improving skin wrinkles, the composition comprising a retinoid and at least one retinoid booster selected from the group consisting of proline amide ethyl imidazole, apigenin, luteolin, and the like. The term "administration" means introducing the composition of the present invention to a patient by any appropriate method, and the administration route of the composition can be a normal route as long as it can reach the target tissue. Due to the property that the composition of the present invention is effective in improving skin wrinkles, the administration route of the composition can be topical application to the skin.

[0034] In one aspect of the present invention, the composition for improving skin wrinkles may be administered daily or intermittently, and the number of administrations per day can be 1 time or divided into 2 to 3 times. Also, the composition of the present invention can be used alone or in combination with other drug treatments for improving skin wrinkles. Considering all the above factors, it is important to administer the minimum amount with maximum effect without side effects, and the dosage can be easily determined by those skilled in the art. The term "individual" means all animals such as mice, rats, livestock, etc., including humans who have or may develop wrinkles or skin wrinkles, and specifically can be mammals including humans.

[0035] The present invention also provides the use of a retinoid and at least one retinoid booster selected from the group consisting of proline amide ethyl imidazole, apigenin, luteolin, and the like for improving skin wrinkles.

[0036] All components disclosed in the present invention preferably do not exceed the maximum usage amounts specified by relevant laws and regulations in countries such as South Korea, China, the United States, Europe, Japan, etc. (for example, regulations regarding cosmetic safety standards (South Korea), Technical Specifications for Cosmetic Safety (China)). That is, preferably, the cosmetic composition or quasi-drug composition according to the present invention contains the components according to the present invention within the limits of the content allowed by the relevant laws and regulations of each country.

Advantages of the Invention

[0037] The cosmetic composition for improving skin wrinkles of the present invention can significantly enhance the effect of retinoids on improving skin wrinkles by suppressing the mechanism by which CYP enzymes oxidatively decompose retinoic acid with a specific retinoid booster compound.

[0038] In addition, the cosmetic composition for improving skin texture or whitening of the present invention can improve skin texture by promoting keratinocyte exfoliation and improving epidermal tissue with retinoids, or can significantly enhance the whitening effect by promoting skin turnover of retinoids.

Brief Description of the Drawings

[0039]

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Mode for Carrying Out the Invention

[0040] Hereinafter, examples and the like will be given in detail to facilitate understanding of the present invention. However, the examples according to the present invention can be changed into other various forms, and the scope of the present invention should not be construed as being limited to the examples described below. The examples of the present invention are provided to more fully explain the present invention to those having average knowledge in the field to which the present invention belongs.

Examples

[0041] Experimental Example 1: Analysis of Retinoid Metabolites by HPLC

[0042] 1 mM of retinoic acid was added to keratinocytes (keratinocyte, HaCat) or the medium (media) and cultured for 48 hours. In this experiment, the medium used was DMEM (Dulbeco’s Modified Eagle’s Medium) with low calcium (Ca 2+ = 0.01 mM) supplemented with FBS (Fetal bovine serum).

[0043] In addition, apigenin or luteolin at 12.5 - 100 mM as a retinoid booster compound and proline amide ethyl imidazole at 125 - 500 mM were added to keratinocytes or the medium together with 1 mM retinoic acid, and they were co-cultured. After culturing each, the culture solution and cell extract were freeze-dried and concentrated. The concentrated sample was resuspended in methanol and then subjected to HPLC analysis. The HPLC analysis conditions were analyzed under 2-step-gradient HPLC conditions of a co-solvent of methanol and 60 mM ammonium acetate (pH 5.75) with reference to the literature of Ingrid C. Gaemers et al. (1998).

[0044] The relative amounts of retinoic acid (RA) oxidation metabolites were analyzed by HPLC, and the results are shown in Figure 1. From the HPLC experimental results shown in Figure 1, since retinoic acid oxidation metabolites were detected from keratinocytes, it can be confirmed that retinoic acid was decomposed. However, when a retinoid booster compound was co-treated with retinoic acid, no retinoic acid oxidation metabolites were detected, and from this, it was confirmed that the retinoid booster compound suppresses the decomposition of retinoic acid.

[0045] Experimental Example 2: Analysis of the retinoic acid decomposition rate by type of retinoid booster compound

[0046] In the same manner as in Experimental Example 1, the decomposition rate of retinoic acid was measured by combining proline amide ethyl imidazole, apigenin, or luteolin as a retinoid booster compound respectively. Decomposition rate = [oxidation metabolite] / [oxidation metabolite + RA]

[0047] A control group of the combination of keratinocytes and retinoic acid was set as a reference of 100%, and liarozole was used as a positive control group.

[0048] From the experimental results shown in Figure 2, it was confirmed that when luteolin or apigenin was treated, the decomposition rate of retinoic acid decreased significantly.

[0049] Experimental Example 3: Measurement of Gene Expression Levels of Retinoic Acid Oxidation / Decomposition Enzymes

[0050] After treating keratinocytes (Hacat) with retinoic acid and a retinoid booster material for 48 hours, RNA was extracted and the gene expression of CYP enzymes (CYP26A1, CYP26B1) was confirmed by RT-qPCR. The untreated group was not treated with retinoic acid, and such an untreated group was set as one standard.

[0051] From the experimental results shown in Figure 3, when keratinocytes were treated with retinoic acid (comparison group), the expression level of the CYP26A1 gene increased by about 8-fold and the expression level of the CYP26B1 gene increased by about 34-fold compared to the untreated group, and was overexpressed. On the other hand, when apigenin or luteolin was treated together with retinoic acid, the expression levels of the CYP26A1 gene and the CYP26B1 gene decreased significantly. It was confirmed from this experiment that the retinoid booster compound significantly reduced the gene expression of CYP enzymes.

[0052] Experimental Example 4: Analysis of Epidermal Thickness Enhancement Effect

[0053] The ex-vivo evaluation of the epidermal thickness enhancement effect was carried out when a retinoid booster compound was used together with retinoic acid. Experiments were conducted by constructing a 3D artificial skin model using fibroblasts and keratinocytes.

[0054] From the experimental results shown in Figure 4, it was confirmed that when prolinamide ethyl imidazole, apigenin or luteolin was used, the enhancement rate of epidermal thickness increased significantly by about 15% - 22% compared to the case of treating with retinoic acid alone on 3D skin.

[0055] Also, from the experimental results shown in Figure 5, it was confirmed that when apigenin 12.5 mM and prolinamide ethyl imidazole 250 mM were treated together, the enhancement rate of epidermal thickness increased significantly compared to the case of treating with retinoic acid alone.

[0056] Experimental Example 5: Measurement of Collagen mRNA Gene Expression Level

[0057] To evaluate the in-vivo efficacy of the retinoid booster, the expression level of the collagen mRNA gene was measured. Since most of the enzymes that degrade retinoids are expressed in keratinocytes, after inducing the expression of these enzymes, co-culture was performed with fibroblasts induced with photoaging. The process of the co-culture is shown schematically in Fig. 6.

[0058] From the results shown in Fig. 7, it was confirmed that the collagen synthesis ability of retinoic acid was significantly increased by the retinoid booster. This is interpreted as a result of the suppression of retinoid degradation and the maintenance of a high effective concentration by the retinoid booster.

[0059] Experimental Example 6: Evaluation of the Effect of Improving Wrinkles on Human Skin

[0060] The effect of improving skin wrinkles was evaluated when formulating a composition containing a retinoid booster together with retinol or retinoic acid. The subjects were 10 women in their 40s to 50s. Among the subjects, those who were 1. pregnant, breastfeeding, or planning to become pregnant within 6 months, 2. had used a topical steroid-containing skin preparation for more than 1 month for the treatment of skin diseases, 3. less than 6 months had passed after participating in the same test, 4. had skin abnormalities such as moles, acne, red bumps, capillary dilation, etc. at the test site, 5. had used the same or similar cosmetics or pharmaceuticals at the test site within 3 months after the start of the test, 6. had received a procedure (skin peeling, Botox, other skin management) at the test site or had it planned within 6 months, 7. had a chronic wasting disease (such as asthma, diabetes, hypertension, etc.), 8. had atopic dermatitis, 9. were excluded from the subjects if it was judged by the principal investigator that the test was difficult for other reasons.

[0061] The composition was applied to the face by dividing it into left and right halves (in the half&half form), and applied to the forehead, nasolabial folds, crow's feet and the entire face (Figure 8). The composition with the formulation described in Table 1 below was used once a day before going to bed (after washing the face at night) for 6 weeks, and the area under the eyes, outer corners of the eyes, and nasolabial folds were measured using Antela 3D.

[0062]

Table 1

[0063] Looking at the results shown in Figure 9, when using the retinoid booster together compared to using retinol alone, the improvement rate of the length of crow's feet was 76%, the improvement rate of the length of the wrinkles under the eyes was 82%, and the improvement rate of the length of nasolabial folds was 118% higher. Also, looking at the results shown in Figure 10, when using the retinoid booster together compared to using retinoic acid alone, the improvement rate of the length of the outer corners of the eyes was 65%, the improvement rate of the length of the wrinkles under the eyes was 138%, and the improvement rate of the length of nasolabial folds was 77% higher.

[0064] From the above experimental results, it was confirmed that the retinoid booster formulation of the present invention can significantly improve the efficacy of not only retinoic acid but also other retinoids.

[0065] Experimental Example 7: Evaluation of Skin Whitening Effect

[0066] The skin wrinkle improvement effects were comparatively evaluated when formulating a composition containing retinol or both retinol and a retinoid booster. The subjects were three women in their 40s to 50s with freckles or pigmentation. The usage formulation was the same as the retinoid booster formulation described in Table 1 above. The face was divided into left and right halves (in a half&half form), and each composition was applied. The evaluation of the skin whitening effect was analyzed using the Unla 3D equipment of Miravex Co., Ltd. Using the analysis tool for pigmentation in this equipment, the variation, uniformity, and overall pigmentation degree of pigments were measured. From the results of the skin pigment improvement degree shown in FIG. 11, it was confirmed that the formulation of the retinoid booster of the present invention significantly increased the skin whitening effect of retinol.

[0067] Experimental Example 8: Evaluation of the effect of improving skin texture

[0068] The improvement effects of skin texture were comparatively evaluated when formulating a composition containing retinol or both retinol and a retinoid booster. For three women in their 40s to 50s, 0.15% retinol and the retinoid booster formulation described in Table 1 were applied to each composition by dividing the face into left and right halves (in a half&half form) for 12 weeks. After 12 weeks, a microscopic skin texture was observed on the forehead area using a fine microscope for measuring skin texture. Using Image J software, the area of the groove of the fine wrinkles was quantified.

[0069] From the results shown in FIG. 12, it was confirmed that the retinoid booster formulation of the present invention significantly increased the improvement effect of retinol on skin texture.

Claims

1. A cosmetic composition for improving skin wrinkles, comprising a retinoid and at least one retinoid booster selected from the group consisting of prolinamide ethylimidazole, apigenin, and luteolin.

2. The cosmetic composition for improving skin wrinkles according to claim 1, wherein the retinoid is contained in an amount of 0.001 to 1% by weight based on the total weight of the composition.

3. The cosmetic composition for improving skin wrinkles according to claim 1, wherein the retinoid booster is contained in an amount of 0.00001 to 2% by weight based on the total weight of the composition.

4. The cosmetic composition for improving skin wrinkles according to claim 1, wherein the weight ratio of the retinoid to the retinoid booster is 1:3 to 1,000 (retinoid:retinoid booster).

5. The cosmetic composition for improving skin wrinkles according to claim 1, wherein the retinoid booster acts on CYP enzymes to suppress the decomposition of retinoic acid.

6. The cosmetic composition for improving skin wrinkles according to claim 1, wherein the retinoid booster suppresses the gene expression of CYP enzymes.

7. A cosmetic composition for improving skin texture, comprising a retinoid and at least one retinoid booster selected from the group consisting of prolinamide ethylimidazole, apigenin, and luteolin.

8. A cosmetic composition for skin whitening, comprising a retinoid and at least one retinoid booster selected from the group consisting of prolinamide ethylimidazole, apigenin, and luteolin.

9. An external pharmaceutical composition for improving skin wrinkles, comprising a retinoid and at least one retinoid booster selected from the group consisting of prolinamide ethylimidazole, apigenin, and luteolin.

10. An external pharmaceutical composition for improving skin texture, comprising a retinoid and at least one retinoid booster selected from the group consisting of prolinamide ethylimidazole, apigenin, and luteolin.

11. An external pharmaceutical composition for skin whitening, comprising a retinoid and at least one retinoid booster selected from the group consisting of prolinamide ethylimidazole, apigenin, and luteolin.

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