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

Abstract

The present disclosure relates to a composition for increasing the efficacy of a retinoid by comprising a retinoid and a material for increasing the efficacy of a retinoid, i.e., a retinoid enhancer. The composition for improving skin wrinkles according to the present disclosure can significantly improve the skin wrinkle improving effect of retinoid by inhibiting a mechanism of oxidative decomposition of retinoic acid by a CYP family enzyme through a specific retinoid enhancer compound.

Description

Technical Field

[0001] This application claims priority based on Korean Application No. 10-2022-0076126 filed on June 22, 2022, and all contents disclosed in the specification and drawings of that application are incorporated herein by reference.

[0002] The present disclosure relates to a composition for increasing the efficacy of a retinoid by including a retinoid and a material for increasing the efficacy of the retinoid, ie, a retinoid enhancer. Background Art

[0003] As the aging population increases and life expectancy increases, the prevention of skin aging, which emphasizes the improvement of skin wrinkles, has attracted increasing attention. The skin, an organ that occupies about 16% of the human body volume, exists on the outermost part of the body and protects our body from the external environment and stimulation. Compared with organs in the body, such skin is always exposed to external stimulation and is therefore vulnerable to attack. In particular, the facial skin is directly exposed to ultraviolet rays and pollutants, making it an organ that is more susceptible to aging than other body skin.

[0004] Skin aging is divided into naturally occurring intrinsic aging and extrinsic aging caused by external factors. As the main factor of intrinsic aging, genetic factors are mentioned, which determine the structure and changes of skin cells and tissues. On the other hand, the factors of extrinsic aging come from the outside, such as malnutrition, ultraviolet rays, environmental pollution, etc., which are different from genetic factors and can be completely prevented and avoided.

[0005] Skin aging due to these factors leads to symptoms such as dry and rough skin, wrinkle formation, decreased elasticity, and pigmentation. In particular, wrinkles and decreased elasticity, which are mentioned as representative symptoms of skin aging, are directly related to the reduction and deformation of collagen and elastin, the main proteins in the dermis. That is, many research reports have shown that skin wrinkles begin with aging of the dermis, and the structure of elastic fibers, namely elastin, changes, causing the skin to sag and wrinkle. Due to the increase in the activity of MMP (matrix metalloproteinase) that decomposes connective tissue components such as collagen in the dermis, collagen synthesis is blocked, resulting in an increase in wrinkles.

[0006] Retinoids (including retinol, retinal, retinoic acid, retinoid derivatives, etc.) are substances that have been certified to increase the thickness of the epidermis, strengthen the ECM layer of the dermis, and increase collagen with the decrease of collagenase (MMP-1), thereby improving skin wrinkles. The above-mentioned retinoic acid is a special medicine, and the above-mentioned retinol or retinoid derivatives are widely used for wrinkle improvement purposes as cosmetics.

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

[0008] However, it is known that CYP family enzymes (cytochrome P450) such as CYP26 expressed in keratinocytes oxidize and decompose retinoic acid. That is, by inhibiting the oxidation reaction of retinoic acid caused by the above CYP family enzymes, the skin wrinkle improvement effect caused by retinoic acid can be increased.

[0009] The necessity and research of ingredients and technologies that can be mixed with retinoids to maximize the effect are ongoing, and Korean registered patent No. 10-0865421 describes a "stable skin care composition comprising a retinoid and a retinoid booster system". However, in order to increase the skin wrinkle effect of retinoic acid, new compounds that can inhibit the action of the above-mentioned CYP family enzymes are actually little known in the technical field to which the present invention belongs, and therefore it is necessary to discover such new compounds. Summary of the invention

[0010] Technical issues

[0011] The problem to be solved by the present disclosure is to provide a composition that can enhance the skin wrinkle improving effect of retinoid by preventing retinoic acid in skin cells from being oxidatively decomposed by CYP family enzymes when retinoid is treated on the skin.

[0012] In addition, the present disclosure aims to provide a composition that can improve skin texture by promoting the exfoliation of retinoids and improving epidermal tissue, or enhance the whitening effect by promoting the skin renewal of retinoids.

[0013] Technical solutions

[0014] As a result of the inventors' unremitting efforts to discover new compounds that can enhance the skin wrinkle improvement effect of retinoids, surprisingly, they found that the specific retinoid enhancer compound disclosed herein can increase the bioavailability of retinoic acid by inhibiting the CYP family enzymes that oxidatively decompose retinoic acid, thereby enhancing the skin wrinkle improvement effect. Therefore, the inventors confirmed that when the specific retinoid enhancer compound is combined with a retinoid to treat wrinkles at the corners of the eyes, wrinkles at the eye bottom, or nasolabial folds, a significant synergistic effect is produced in improving skin wrinkles compared to the treatment of retinoid alone, thereby completing the present invention.

[0015] The present disclosure provides a cosmetic composition for improving skin wrinkles, comprising a retinoid and any one or more retinoid enhancers selected from the group consisting of prolinamidoethyl imidazole, apigenin, and luteolin.

[0016] The present inventors confirmed that proline amide ethyl imidazole, apigenin or luteolin inhibited the decomposition of retinoic acid by cell metabolite analysis, thereby confirming that they can function as retinoid enhancers (experimental examples 1, 2). In addition, the present inventors found that the above-mentioned retinoid enhancer compounds significantly inhibited the gene expression of CYP family enzymes, thereby confirming the inhibition of the decomposition of retinoic acid caused by CYP family enzymes (experimental example 3). In addition, the present inventors confirmed that the combination of retinoic acid and retinoid enhancers strengthened the thickness of the epidermis (experimental example 4), and confirmed that the expression of collagen mRNA was also increased (experimental example 5), and actually confirmed that when the combination of retinoic acid and retinoid enhancers was applied to the skin, a wrinkle improvement effect was significantly shown (experimental example 6). As described above, proline amide ethyl imidazole, apigenin or luteolin can inhibit the oxidative decomposition of retinoic acid converted by retinoids by inhibiting CYP family enzymes, thereby significantly increasing the skin wrinkle improvement effect caused by retinoic acid.

[0017] In one aspect of the present disclosure, the above-mentioned retinoid refers to a compound having a vitamin A (retinol) skeleton, and may include retinol, retinal, retinoic acid or a retinoid derivative, etc. The above-mentioned retinoic acid may include tretinoin (all-trans-retinoic acid), isotretinoin (13-cis-retinoic acid (13-cis retinoic acid)) or alitretinoin (9-cis-retinoic acid (9-cis retinoic acid)), etc. The above-mentioned retinoid derivative may include retinyl palmitate, retinyl acetate, etretinate, acitretin, adapalene, bexarotene, tazarotene or polyethoxylated retinamide, etc.

[0018] In one aspect of the present disclosure, the content of the above-mentioned retinoid can be 0.001 to 1 weight%, preferably 0.005 to 0.8 weight%, more preferably 0.01 to 0.5 weight, and most preferably 0.02 to 0.3 weight, relative to the total weight of the composition. Since the above-mentioned retinoid may cause skin irritation when applied to the skin, its application amount is limited. However, in the present disclosure, since the retinoid enhancer is combined with the retinoid so as not to contain an excessive amount of retinoid, the skin wrinkle improvement effect can be significantly increased without skin irritation. When the content of the above-mentioned retinoid exceeds 1 weight% relative to the total weight of the composition, it is worried that it may cause skin irritation, and when it is less than 0.001 weight%, the skin wrinkle improvement effect may not be fully exerted.

[0019] In one aspect of the present disclosure, the content of the retinoid enhancer may be 0.00001 to 2 weight %, preferably 0.001 to 1.5 weight %, and more preferably 0.05 to 1 weight %, relative to the total weight of the composition. When the content of the retinoid enhancer is less than 0.00001 weight %, relative to the total weight of the composition, the effect of the retinoid efficacy enhancer may not be fully exerted, and when the content exceeds 2 weight %, it may cause skin irritation.

[0020] In one aspect of the present disclosure, the weight ratio of the retinoid to the retinoid enhancer can be 1:3 to 1000, preferably 1:4 to 950, more preferably 1:5 to 900 (retinoid: retinoid enhancer). When the weight ratio of the two components is within the above range, the retinoic acid decomposition inhibitory effect caused by the retinoid enhancer is increased, thereby significantly improving the skin wrinkle improvement effect.

[0021] In one aspect of the present disclosure, when the retinoid enhancer is apigenin, the weight ratio of the retinoid to the retinoid enhancer may be 1:3 to 50, preferably 1:4 to 35, and more preferably 1:5 to 20. When the retinoid enhancer is luteolin, the weight ratio of the retinoid to the retinoid enhancer may be 1:3 to 60, preferably 1:4 to 50, and more preferably 1:5 to 40. When the retinoid enhancer is prolineamide ethyl imidazole, the weight ratio of the retinoid to the retinoid enhancer may be 1:40 to 1000, preferably 1:50 to 950, and more preferably 1:55 to 900. Apigenin and luteolin inhibit the gene expression of CYP family enzymes, and prolineamide ethyl imidazole directly acts on CYP family enzymes to inhibit the decomposition of retinoic acid. According to the mechanism of action of each of these retinoid enhancers, when the weight ratio is within the above-mentioned range, the effect of increasing the efficacy of retinoid is excellently exhibited.

[0022] In one aspect of the present disclosure, the above-mentioned cosmetic composition for improving skin wrinkles can be prepared into a dosage form selected from the group including solutions, external ointments, creams, foams, nourishing lotions, softening lotions, facial masks, skin softeners, emulsions, primers, essences, soaps, liquid cleansers, bath preparations, sunscreens, sunscreen oils, suspensions, emulsions, pastes, gels, lotions, powders, soaps, cleansers containing surfactants, oils, powder foundations, emulsion foundations, wax foundations, patches, and sprays, but is not limited thereto.

[0023] In one aspect of the present disclosure, the cosmetic composition for improving skin wrinkles may additionally include one or more substances selected from the group consisting of oil, water, surfactant, moisturizer, alcohol, thickener, chelating agent, pigment, preservative and fragrance, but is not limited thereto. In addition, the cosmetic composition of the present disclosure may include a cosmetically acceptable carrier.

[0024] In one aspect of the present disclosure, when the dosage form of the cosmetic composition for improving skin wrinkles is an ointment, a paste, a cream, or a gel, as a carrier component, animal oil, vegetable oil, wax, paraffin, starch, tragacanth gum, cellulose derivatives, polyethylene glycol, silicone, bentonite, silicon dioxide, talc, zinc oxide, or a mixture thereof can be used.

[0025] In one aspect of the present disclosure, when the dosage form of the cosmetic composition for improving skin wrinkles is powder or spray, as the carrier component, lactose, talc, silicon dioxide, aluminum hydroxide, calcium silicate, polyamide powder, or a mixture thereof can be used. In particular, in the case of a spray, a propellant such as chlorofluorocarbon, propane / butane or dimethyl ether can be further included.

[0026] In one aspect of the present disclosure, when the dosage form of the cosmetic composition for improving skin wrinkles is a solution or an emulsion, a solvent, a solubilizer, or an emulsifier is used as a carrier component, for example, water, ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, or 1,3-butylglycoloil, etc. In addition, cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol aliphatic esters, polyethylene glycol, or fatty acid esters of sorbitan, etc. can be used as the above-mentioned carrier component.

[0027] In one aspect of the present disclosure, 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 suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitan ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth gum can be used.

[0028] In one aspect of the present disclosure, when the dosage form of the cosmetic composition for improving skin wrinkles is a capsule, it can be formulated into the form of alginate capsules, agar capsules, gelatin capsules, wax capsules, or double capsules, but is not limited thereto.

[0029] In one aspect of the present disclosure, the above-mentioned cosmetic composition for improving skin wrinkles may contain, in addition to retinoids and retinoid enhancers, commonly used auxiliary agents, such as hydrophilic or lipophilic gelling agents, hydrophilic or lipophilic active agents, preservatives, antioxidants, solvents, fragrances, fillers, blocking agents, pigments, odor absorbers, or dyes.

[0030] In addition, the present disclosure provides a cosmetic composition for whitening skin or improving skin texture, comprising a retinoid and any one or more retinoid enhancers selected from the group consisting of prolineamide ethylimidazole, apigenin, and luteolin.

[0031] In addition, the present disclosure provides a pharmaceutical composition for improving skin wrinkles, which comprises a retinoid; and any one or more retinoid enhancers selected from the group including proline amide ethyl imidazole, apigenin and luteolin. The effective amount of the retinoid and the retinoid enhancer in the above pharmaceutical composition can vary according to the form of the pharmaceutical composition product, the method of applying the above retinoid and the retinoid enhancer to the skin, and the time of staying on the skin. The above pharmaceutical composition can be in various oral or non-oral dosage forms. When the dosage form is formed, a diluent or excipient such as a commonly used filler, extender, binder, wetting agent, disintegrant, surfactant, etc. can be used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. Such solid preparations are prepared by mixing one or more compounds with at least one or more excipients such as starch, calcium carbonate, sucrose, lactose, or gelatin. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid preparations for oral administration include suspensions, internal liquids, emulsions, syrups, etc. In addition to the commonly used simple diluents, i.e., water and liquid paraffin, various excipients may also be included, such as wetting agents, sweeteners, aromatics, preservatives, etc. Preparations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, and emulsions. As non-aqueous solvents and suspension solvents, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, etc. may be used.

[0032] In addition, the present disclosure provides a food composition for improving skin wrinkles, which comprises a retinoid; and any one or more retinoid enhancers selected from the group including proline amide ethyl imidazole, apigenin and luteolin. In addition to the above-mentioned retinoids and retinoid enhancers, the above-mentioned food composition may also contain food additives that are permitted in food science. The above-mentioned food additives refer to constituent elements that can be added to food for preservation, and those skilled in the art can appropriately select and use them. As examples of food additives, various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers, pectin acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, or carbonating agents used in carbonated beverages, etc. may be included.

[0033] In addition, the present disclosure provides a quasi-pharmaceutical composition for improving skin wrinkles, which contains a retinoid; and any one or more retinoid enhancers selected from the group including proline amide ethyl imidazole, apigenin and luteolin. In addition to the above-mentioned ingredients, the above-mentioned quasi-pharmaceutical composition may also contain a pharmaceutically acceptable carrier, excipient or diluent as needed. The above-mentioned pharmaceutically acceptable carrier, excipient or diluent is not limited as long as it does not impair the effect of the present invention, and may include, for example, fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, fragrances, preservatives, etc. The above-mentioned quasi-pharmaceutical composition can exemplify disinfectant cleaners, bath foams, ointment liquids, wet wipes, coatings, etc., but is not limited thereto, and the formulation method, dosage, utilization method, constituent components, etc. of the quasi-pharmaceutical can be appropriately selected from conventional techniques known in the technical field.

[0034] In addition, the present disclosure provides a method for improving skin wrinkles, comprising the step of administering to an individual a composition for improving skin wrinkles comprising a retinoid; and any one or more retinoid enhancers selected from the group including prolineamide ethyl imidazole, apigenin and luteolin. The above-mentioned "administration" refers to introducing the composition of the present disclosure into a patient by any appropriate method, and the administration route of the above-mentioned composition can be administered by any general route as long as it can reach the target tissue. Based on the characteristics of the composition of the present disclosure that is effective in improving skin wrinkles, the administration route of the above-mentioned composition can be administered by applying it on the skin.

[0035] In one aspect of the present disclosure, the above-mentioned composition for improving skin wrinkles can be administered daily or intermittently, and the number of administrations per day can be divided into 1 time or 2 to 3 times for administration. In addition, in order to improve skin wrinkles, the composition of the present disclosure can be used alone or in combination with other drug treatments. Taking all the above factors into consideration, it is important to administer the amount that can achieve the maximum effect with the minimum amount without side effects, and the dosage can be easily determined by those skilled in the art. The above-mentioned "individual" refers to all animals including humans, mice, rats, livestock, etc. that have or may develop wrinkles or skin wrinkles, and specifically, it can be mammals including humans.

[0036] In addition, the present disclosure provides a retinoid; and any one or more retinoid enhancers selected from the group consisting of prolineamide ethylimidazole, apigenin, and luteolin for use in improving skin wrinkles.

[0037] All ingredients described in the present disclosure preferably do not exceed the maximum usage values ​​specified in relevant laws or regulations of Korea, China, the United States, Europe, Japan, etc. (e.g., relevant regulations such as cosmetic safety standards (Korea), cosmetic safety technical regulations (China)). That is, preferably, the cosmetic composition or quasi-drug composition of the present disclosure includes the ingredients of the present disclosure within the content limits permitted by the relevant laws or regulations of each country.

[0038] Effects of the Invention

[0039] The cosmetic composition for improving skin wrinkles disclosed in the present invention can inhibit the mechanism of oxidative decomposition of retinoic acid by CYP family enzymes through a specific retinoid enhancer compound, thereby significantly improving the skin wrinkle improvement effect of retinol.

[0040] In addition, the cosmetic composition for improving skin texture or for whitening disclosed herein can improve skin texture by promoting the exfoliation of keratin and improving epidermal tissue caused by retinoids, or significantly improve the whitening effect by promoting the skin renewal of retinoids. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 This is the result of analyzing retinoid metabolites by HPLC in Experimental Example 1.

[0042] Figure 2 These are the results of analyzing the retinoic acid decomposition rate by type of retinoid enhancer compound in Experimental Example 2.

[0043] Figure 3 These are the results of measuring the gene expression levels of CYP family enzymes when retinoic acid and retinoid enhancers were treated in Experimental Example 3.

[0044] Figure 4 and Figure 5 This is the measurement result of the epidermal thickness enhancement rate when the retinoid enhancer and retinoic acid were treated together in Experimental Example 4.

[0045] Figure 6 This is a schematic diagram for explaining the co-culture process with photoaging-induced fibroblasts in Experimental Example 5.

[0046] Figure 7 This is the measurement result of the collagen mRNA gene expression level when the retinoid enhancer and retinoic acid were treated together in Experimental Example 5.

[0047] Figure 8 This is a schematic diagram for explaining that in Experimental Example 6, the prescription composition was applied to the face in a half & half form.

[0048] Fig. 9 These are the evaluation results of the improvement rate of skin wrinkles when the retinoid enhancer was used together with retinol in Experimental Example 6.

[0049] Fig.10 These are the evaluation results of the improvement rate of skin wrinkles when the retinoid enhancer and retinoic acid were treated together in Experimental Example 6.

[0050] Fig.11 These are the evaluation results of the skin whitening effect when the retinoid enhancer was treated together with retinol in Experimental Example 7.

[0051] Fig.12 These are the evaluation results of the skin texture improvement effect when the retinoid enhancer is treated together with retinol in Experimental Example 8. DETAILED DESCRIPTION

[0052] Hereinafter, in order to help the understanding of the present invention, embodiments and the like will be given for detailed description. However, the embodiments of the present invention may be deformed into various other forms, and the scope of the present invention should not be interpreted as being limited to the following embodiments. The embodiments of the present invention are provided to more completely describe the present invention to those of ordinary skill in the art to which the present invention belongs.

[0053] Experimental Example 1: Analysis of retinoid metabolites by HPLC

[0054] 1 mM retinoic acid was added to keratinocytes (Hacat) or culture medium and cultured for 48 hours. In this experiment, the culture medium used was low calcium (Ca) supplemented with FBS (Fetal bovine serum). 2+ =0.01 mM) DMEM (Dulbeco's Modified Eagle's Medium).

[0055] In addition, 12.5-100 mM apigenin or luteolin and 125-500 mM proline amide ethyl imidazole as retinoid enhancer compounds were added to keratinocytes or culture medium together with 1 mM retinoic acid and cultured. After culturing, the culture fluid and cell extract were concentrated by freeze drying. The concentrated sample was resuspended in methanol and then subjected to HPLC analysis. The HPLC analysis conditions were referred to the literature of Ingrid C. Gaemers et al. (1998), and the analysis was performed using a co-solvent 2-step gradient HPLC condition of methanol and ammonium acetate 60 mM (pH 5.75).

[0056] The relative amounts of retinoic acid (RA) oxidative metabolites were analyzed by HPLC, and the results are shown in Figure 1 In. From Figure 1 From the HPLC test results shown, retinoic acid oxidation metabolites were detected in keratinocytes, confirming that retinoic acid was decomposed. However, when the retinoid enhancer compound was treated with retinoic acid, retinoic acid oxidation metabolites were not detected, confirming that the retinoid enhancer compound inhibited the decomposition of retinoic acid.

[0057] Experimental Example 2: Analysis of retinoic acid decomposition rate by type of retinoid enhancer compound

[0058] In the same manner as in Experimental Example 1 above, prolinamide ethyl imidazole, apigenin or luteolin were combined as retinoid enhancer compounds, and the decomposition rate of retinoic acid was measured.

[0059] Decomposition rate = [oxidative metabolites] / [oxidative metabolites + RA]

[0060] The control group of keratinocytes and retinoic acid combination was set as a standard of 100%, and liarozole was used as a positive control group.

[0061] from Figure 2 From the experimental results shown, it was confirmed that the decomposition rate of retinoic acid was significantly reduced when luteolin or apigenin was treated.

[0062] Experimental Example 3: Measurement of gene expression of retinoic acid oxidase / degradation enzyme

[0063] Retinoic acid and retinoid enhancer materials were treated in keratinocytes (Hacat) for 48 hours, and then RNA was extracted and the gene expression of CYP family enzymes (CYP26A1, CYP26B1) was confirmed by RT-qPCR. The untreated group was treated without retinoic acid, and such untreated group was set as a standard of 1.

[0064] from Figure 3 From the experimental results shown, when retinoic acid was treated in keratinocytes (control group), the expression of CYP26A1 gene increased by about 8 times and the expression of CYP26B1 gene increased by about 34 times compared with the untreated group, thus overexpressing. At the same time, when apigenin or luteolin was treated with retinoic acid, the expression of CYP26A1 gene and CYP26B1 gene was significantly reduced. Through this experiment, it was confirmed that the above-mentioned retinoid enhancer compound significantly reduced the gene expression of CYP family enzymes.

[0065] Experimental Example 4: Analysis of the effect of strengthening the epidermis thickness

[0066] The effect of enhancing epidermal thickness when a retinoid enhancer compound is used together with retinoic acid was evaluated ex-vivo. The experiment was conducted by constructing a 3D artificial skin model using fibroblasts and keratinocytes.

[0067] from Figure 4 From the experimental results shown, it was confirmed that, in 3D skin, when prolineamide ethyl imidazole, apigenin or luteolin was used, the epidermal thickness enhancement rate was significantly increased by about 15% to 22% compared with retinoic acid alone.

[0068] In addition, from Figure 5 From the experimental results shown, it was confirmed that the epidermal thickness enhancement rate was significantly increased when 12.5 mM apigenin and 250 mM prolineamide ethyl imidazole were treated together, compared with the treatment of retinoic acid alone.

[0069] Experimental Example 5: Measurement of collagen mRNA gene expression

[0070] In order to evaluate the in vitro efficacy of retinoid enhancers, the expression of collagen mRNA gene was measured. Since the enzymes that decompose retinoids are mostly expressed in keratinocytes, the expression of these enzymes was induced and then co-cultured with photoaging-induced fibroblasts. The above co-culture process is schematically shown in Figure 6 middle.

[0071] from Figure 7 From the results shown, it was confirmed that the collagen synthesis ability of retinoic acid was significantly increased by the retinoid enhancer. This is interpreted as the result of the retinoid enhancer inhibiting the decomposition of retinoid and maintaining a high effective concentration.

[0072] Experimental Example 6: Evaluation of the wrinkle improvement effect on human skin

[0073] When a composition containing retinol or retinoic acid and a retinoid enhancer is prescribed, the skin wrinkle improvement effect is evaluated. The subjects were 10 women in their 40s and 50s. Among the subjects, ① those who were pregnant, breastfeeding, or planned to become pregnant within 6 months, ② those who used steroid-containing external skin preparations for more than 1 month to treat skin diseases, ③ those who had not passed 6 months since participating in the same test, ④ those who had skin abnormalities such as moles, acne, erythema, and telangiectasia at the test site, ⑤ those who used the same or similar cosmetics or pharmaceuticals at the test site within 3 months of the start of the test, ⑥ those who had undergone or planned to undergo surgery (skin peeling, botulinum toxin (Botox), other skin care) at the test site within 6 months, ⑦ those who suffered from chronic wasting diseases (asthma, diabetes, hypertension, etc.), ⑧ those who suffered from atopic dermatitis, and ⑨ In addition, those who were judged to be difficult to test based on the judgment of the main experimenter were excluded from the test.

[0074] The composition is applied to the forehead, septal lines, eye wrinkles, and the front of the face in a half & half form ( Figure 8 ). Use the composition of the prescription described in Table 1 below once a day before going to bed (after washing the face at night), and measure the fundus, canthus, and splayed wrinkles using Antera 3D for 6 weeks.

[0075] [Table 1]

[0076]

[0077] from Fig. 9 The results shown in the study showed that when the retinoid enhancer was used together with the retinol enhancer, the improvement rate of the length of the corner wrinkles increased by 76%, the improvement rate of the length of the fundus wrinkles increased by 82%, and the improvement rate of the length of the splayed wrinkles increased by 118% compared with retinol alone. Fig.10 From the results shown, when used together with a retinoid enhancer, the improvement rate of canthal wrinkle length increased by 65%, the improvement rate of fundus wrinkle length increased by 138%, and the improvement rate of splay wrinkle length increased by 77% compared to retinoic acid alone.

[0078] From the above experimental results, it can be confirmed that the retinoid enhancer prescription disclosed in the present invention can not only significantly improve the efficacy of retinoic acid, but also significantly improve the efficacy of other retinoids.

[0079] Experimental Example 7: Evaluation of skin whitening effect

[0080] When a composition containing retinol or retinol and a retinoid enhancer was prescribed, the skin wrinkle improvement effect was compared and evaluated. The subjects were 3 women in their 40s to 50s with melasma or pigmentation. The prescription used was the same as the retinoid enhancer prescription described in Table 1 above. Each composition was applied to the face in a half & half form for 12 weeks, and for the evaluation of the skin whitening effect, analysis was performed using the Miravex Antera 3D device. The pigmentation was measured using an analysis tool in the corresponding device to measure the variation, uniformity, and overall pigmentation of the pigment. From Fig.11 From the results of skin pigmentation improvement shown, it was confirmed that the retinoid enhancer formulation of the present disclosure significantly increased the skin whitening effect of retinol.

[0081] Experimental Example 8: Evaluation of skin texture improvement effect

[0082] When a composition containing retinol or retinol and a retinoid enhancer is prescribed, the skin texture improvement effect is compared and evaluated. Three women in their 40s and 50s were used as subjects, and each composition was applied in a half & half form on the face for 12 weeks using 0.15% retinol and the retinoid enhancer prescription described in Table 1. After 12 weeks, the skin texture at the microscopic level was observed on the forehead using a skin texture measurement microscope. The area of ​​fine wrinkle grooves was quantified using Image J software.

[0083] from Fig.12 From the results shown, it was confirmed that the retinoid enhancer formulation of the present disclosure significantly increased the skin texture improving effect of retinol.

Claims

1. A cosmetic composition for improving skin wrinkles, comprising a retinoid; and at least one retinoid enhancer selected from the group consisting of prolinamidoethyl imidazole, apigenin and luteolin.

2. The cosmetic composition for improving skin wrinkles according to claim 1, wherein: The content of the retinoid is 0.001 wt % to 1 wt % relative to the total weight of the composition.

3. The cosmetic composition for improving skin wrinkles according to claim 1, wherein: The content of the retinoid enhancer is 0.00001 to 2 weight % relative to 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 enhancer, ie, retinoid:retinoid enhancer, is 1:3 to 1000.

5. The cosmetic composition for improving skin wrinkles according to claim 1, wherein: The above-mentioned retinoid enhancers act on CYP family enzymes to inhibit the decomposition of retinoic acid.

6. The cosmetic composition for improving skin wrinkles according to claim 1, wherein: The above-mentioned retinoid enhancers inhibit the gene expression of CYP family enzymes.

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

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

9. A quasi-drug composition for improving skin wrinkles, comprising a retinoid; and at least one retinoid enhancer selected from the group consisting of prolineamide ethyl imidazole, apigenin and luteolin.

10. A quasi-drug composition for improving skin texture, comprising a retinoid; and at least one retinoid enhancer selected from the group consisting of prolineamide ethyl imidazole, apigenin and luteolin.

11. A quasi-drug composition for whitening skin, comprising a retinoid; and at least one retinoid enhancer selected from the group consisting of prolineamide ethyl imidazole, apigenin and luteolin.

Images