Skin external composition

Abstract

There has been a demand for development of a product that acts on both sagging pores and enlarged pores. As a result of development of cosmetics having a combination of multiple active ingredients, the present invention provides a skin external composition comprising retinol, glycylglycine, and tranexamic acid. Such a skin external composition can exhibit an effect of improving both enlarged pores and sagging pores.

Description

Topical composition for skin 【0001】 The present invention relates to a composition for applying to the skin. More specifically, it relates to a topical composition for the purpose of improving the visibility of pores on the skin. 【0002】 Although the number of pores on the skin is innate and does not change, clogged comedones, deposition of darkening, and opening of the pores make the pores prominent and greatly affect the aesthetic appearance. The opening of pores is roughly classified into open pores that open in a mortar shape due to abnormal keratinization and sagging pores that are prominent due to skin sagging. Open pores are caused by disruption of the turnover of the stratum corneum due to the influence of unsaturated fatty acids present in the secreted sebum. On the other hand, sagging pores are caused by a decrease in collagen in the dermis layer, resulting in skin sagging. There is a demand to suppress the visibility of pores through skin care, and various methods such as cosmetics such as peeling packs, AHA / BHA pads, oil cleansing, enzyme cleansing, and beauty treatments such as hydrafacial are provided as pore improvement solutions. However, research aiming at a highly satisfactory pore improvement effect for both sagging pores and open pores has been slow to progress. So far, as agents that exhibit a peeling action on the cutin, acids such as glycolic acid, salicylic acid, and lactic acid are known, and peeling agents containing any one or a combination of these are commercially available for the purpose of improving open pores. In addition, it has been reported that by combining glycylglycine with β-alanine and phenaceturic acid, an open pore improvement effect is exhibited, and it has been reported as an abnormal keratinization inhibitor and a pore shrinking agent (Patent Document 1: Japanese Patent No. 5241058). In addition, as a beauty method for pore care, a method characterized by applying glycylglycine to the skin and then performing iontophoresis has also been reported (Patent Document 2: Japanese Patent Application Laid-Open No. 2010-260796). Furthermore, it has been reported that combining retinol and glycylglycine improves sagging pores (Patent Document 3: International Publication No. 2023 / 068090). In the combination in this document, no significant difference was found in open pores and pore area. 【0003】 Japanese Patent No. 5241058 Japanese Patent Application Laid-Open No. 2010-260796 International Publication No. 2023 / 068090 【0004】 Cosmetics containing glycylglycine are known to have an effect on improving enlarged pores, and a combination of retinol and glycylglycine has been shown to improve sagging pores. However, there has been a need for the development of products that act on both sagging and enlarged pores. 【0005】 We have been developing cosmetics that combine multiple active ingredients, and have found that by combining retinol, glycylglycine, and tranexamic acid, it is possible to improve both enlarged pores and sagging pores, which led to the present invention. Therefore, the present invention relates to the following: [1] A topical skin composition comprising retinol or a retinol derivative, glycylglycine and / or a salt thereof, and tranexamic acid and / or a salt thereof. [2] 1.0 IU / g to 5.0 × 10 5[1] A topical skin composition according to item 1, comprising IU / g retinol or a retinol derivative, 0.05% to 3% by mass glycylglycine and / or a salt thereof, and 0.1% to 2% by mass tranexamic acid and / or a salt thereof. [3] A topical skin composition according to item 1 or 2, wherein the retinol derivative is selected from the group consisting of retinoic acid or a salt thereof, retinal, retinoid, and retinyl palmitate. [4] A topical skin composition according to any one of items 1 to 3, for use in improving the appearance of pores. [5] A topical skin composition according to item 4, wherein the appearance of pores is due to enlarged pores caused by epidermal inflammation or parakeratinization. [6] A topical skin composition according to item 5, for reducing enlarged pores. [7] Use of a topical skin composition according to any one of items 1 to 3 for the manufacture of a cosmetic or pharmaceutical for improving the appearance of pores. [8] The use described in item 7, wherein the enlarged pores are caused by epidermal inflammation or incomplete keratinization. [9] The topical skin composition described in item 7 for reducing enlarged pores.

[10] A cosmetic method for improving enlarged pores, comprising applying the topical skin composition described in any one of items 1 to 3 to the skin of a person concerned with enlarged pores.

[11] The cosmetic method described in item 10, wherein the enlarged pores are caused by epidermal inflammation or incomplete keratinization.

[12] The cosmetic method described in item 10 for reducing enlarged pores.

[13] A cosmetic method for improving enlarged pores, comprising applying retinol or a retinol derivative, glycylglycine and / or a salt thereof, and tranexamic acid and / or a salt thereof to the skin of a person concerned with enlarged pores.

[14] A cosmetic method for improving the appearance of pores, comprising applying retinol or a retinol derivative, glycylglycine and / or a salt thereof, and tranexamic acid and / or a salt thereof simultaneously or separately. 【0006】 It has an improving effect on both sagging pores and enlarged pores. In particular, it can show improvement in a relatively short period of time, as short as 8 weeks after continuous use. 【0007】Figure 1 shows the changes in (A) pore area and (B) pore aspect ratio in replica analysis when a formulation containing retinol, glycylglycine, and tranexamic acid (active) or a control formulation (placebo) was applied to the skin for 4 weeks and 8 weeks. Figure 2(A) shows the changes in pore area in image analysis when a formulation containing retinol, glycylglycine, and tranexamic acid (active) was applied to the skin for 4 weeks and 8 weeks. The results with a placebo are shown side by side as a control. Figure 2(B) shows the changes in pore aspect ratio in image analysis when a formulation containing retinol, glycylglycine, and tranexamic acid (active) was applied to the skin for 4 weeks and 8 weeks. The results with a placebo are shown side by side as a control. Figure 3 shows the changes in skin moisture content when a formulation containing retinol, glycylglycine, and tranexamic acid (active) and a placebo were applied to the skin for 4 weeks and 8 weeks, respectively. The ratio of active formulation to placebo is shown. Figure 4 shows the changes in skin sebum content when a formulation containing retinol, glycylglycine, and tranexamic acid (active) and a placebo were applied to the skin for 4 weeks and 8 weeks, respectively. Figure 5 shows the results of analyzing HSS images using an HSS pore analysis application when (A) a formulation containing retinol, glycylglycine, and tranexamic acid (active) and (B) a placebo were applied to the skin for 4 weeks and 8 weeks, respectively. Figure 6 shows the results of self-assessments and physician evaluations of pore size after continuous application of a formulation (active) containing retinol, glycylglycine, and tranexamic acid to the skin for 4 weeks and 8 weeks. 【0008】 The present invention relates to a topical skin composition comprising retinol or a retinol derivative, glycylglycine and / or a salt thereof, and tranexamic acid and / or a salt thereof. 【0009】Retinol is a compound classified as vitamin A, and its CAS number is 68-26-8. Retinol derivatives can be any compound that possesses the vitamin A activity of retinol, and are not particularly limited as long as they can be used in the fields of cosmetics, pharmaceuticals, quasi-drugs, etc. Examples of retinol derivatives include retinyl palmitate, retinyl acetate, retinal, tretinoin, isotretinoin, retinoic acid, and all-trans retinoic acid. The amount of retinol and / or its derivatives included is not particularly limited as long as the effects of the present invention are achieved, but from the viewpoint of exhibiting a pore-improving effect, the amount of retinol and / or its derivatives included is preferably 1.0 IU / g or more, and 0.3 × 10⁻⁶ 2 A concentration of IU / g or higher is even more preferable. From the viewpoint of reducing skin irritation, the amount of retinol and / or its derivatives should be 5 × 10 5 Preferably IU / g or less, 1.0 × 10 5 A value of IU / g or less is even more preferable. Here, IU stands for International Unit. 【0010】 Glycylglycine is an amphoteric compound having both a carboxyl group and an amino group, and is a compound with CAS number 556-50-3. Glycylglycine exhibits different dissociation states depending on pH, with an isoelectric point of approximately 5.65, a pKa1 of 3.12, and a pKa2 of 8.17. When the pH is lower than the isoelectric point, glycylglycine becomes positively charged, while when the pH is higher than the isoelectric point, it becomes negatively charged. The amount of glycylglycine included is not particularly limited as long as the effects of the present invention are achieved, but from the viewpoint of exhibiting a pore-improving effect, the amount of glycylglycine is preferably 0.05% by mass or more, and more preferably 0.5% by mass or more. From the viewpoint of exhibiting an effect commensurate with an increase in the amount included, the amount of glycylglycine is preferably 3.0% by mass or less, and more preferably 2.0% by mass or less. 【0011】Tranexamic acid is a synthetic amino acid having a carboxyl group and an amino group, and is a compound with CAS number 1197-18-8. Tranexamic acid is known to exhibit anti-inflammatory, anti-plasmin, and skin-whitening effects, and has been developed as a hemostatic agent, anti-inflammatory agent, and skin-whitening agent. The amount of tranexamic acid and / or its salt is not particularly limited as long as the effects of the present invention are achieved, but from the viewpoint of exhibiting a pore-improving effect, the amount of tranexamic acid is preferably 0.1% by mass or more, and more preferably 1% by mass or more. From the viewpoint of exhibiting an effect commensurate with the increase in the amount, the amount of tranexamic acid is preferably 2% by mass or less. 【0012】 The active ingredient salts incorporated into the topical skin composition according to the present invention are not particularly limited as long as they are used for topical skin application, but examples of inorganic salts include hydrochloride, sulfate, phosphate, hydrobromide, sodium salt, potassium salt, magnesium salt, calcium salt, and ammonium salt. Examples of organic salts include acetate, lactate, maleate, fumarate, tartrate, citrate, methanesulfonate, p-toluenesulfonate, triethanolamine salt, diethanolamine salt, and amino acid salt. The salt compounds used in the present invention can be prepared by known methods. 【0013】 A topical skin composition refers to a composition that can be applied to the skin. It contains the active ingredients glycylglycine and / or its salts, tranexamic acid and / or its salts, and retinol and / or its derivatives, but may also contain other active ingredients and any other ingredients. The topical skin composition of the present invention is used for pore care. More specifically, it has an improving effect on both sagging pores and enlarged pores. Therefore, the topical skin composition of the present invention can be described as a composition for pore care, pore reduction, treatment, prevention or reduction of incomplete keratinization, and can exert an improving effect on pores, i.e., an improving effect on enlarged, noticeable, clogged, and / or blackhead pores, and a pore contracting effect. In particular, the topical skin composition of the present invention relates to a composition for improving both symptoms of sagging pores and enlarged pores. The pH of the topical skin composition of the present invention is not particularly limited as long as it is a pH at which the pore improving effect of the present invention can be exerted. 【0014】 While the number of pores does not change with age, pores become more noticeable with age. Pores become enlarged and more noticeable due to increased sebum production, which leads to clogged pores. Additionally, unsaturated fatty acids in the sebum act on keratinocytes around the pores, causing incomplete keratinization, which makes the pores appear funnel-shaped and more noticeable. The entire area around the pore that is indented in a funnel shape is recognized as a pore, and when this area widens, the pore is perceived as open. Such pores can be specifically called enlarged pores. When enlarged pores are noticeable, the stratum corneum in the funnel-shaped area around the pore is often in a state of incomplete keratinization and is accompanied by inflammation. Enlarged pores can be identified by their shape, which is generally circular. Incomplete keratinization refers to a state where stratum corneum differentiation has not occurred properly, and nuclei that should normally disappear during stratum corneum differentiation remain. Therefore, enlarged pores can also be identified by the presence or absence of nuclei in the epidermal layer. Skin exhibiting incomplete keratinization has poor skin barrier function and moisturizing ability, resulting in dry and rough skin, as well as enlarged pores. One of the causes of incomplete keratinization is increased production of unsaturated fatty acids in sebum. While not intended to be purely theoretical, it is thought that unsaturated fatty acids accumulated in the pores act on epidermal cells, disrupting the turnover of the stratum corneum, leading to incomplete keratinization and enlarged pores. This condition is mainly seen on the tip of the nose, cheeks, and T-zone. 【0015】 On the other hand, in addition to enlarged pores, there is also a type of pore that is called sagging pores. Sagging pores are thought to be caused by a decrease in the elasticity of the dermis layer, resulting in skin sagging. As the skin sags, the epidermis is pulled, and the round pores become deformed, making them more noticeable. They are mainly seen on the cheeks and around the nasolabial folds. Sagging pores and enlarged pores can be classified by their shape. Enlarged pores and sagging pores can be represented by their aspect ratio, by selecting the longest side and the shortest side perpendicular to that long side. The longest side is set to be the longest in the pore, and the shortest side is set to be the longest of the shortest sides perpendicular to that long side. By setting the initial aspect ratio to 1, the change over time can be determined. 【0016】 Enlarged pores and sagging pores have different causes and require different treatments. For enlarged pores, treating, improving, or reducing incomplete keratinization can make them less noticeable. On the other hand, for sagging pores, care of the dermis layer is considered necessary, and to restore elasticity, activation of dermal fibroblasts is required, such as increasing the expression of collagen, elastin, and proteoglycans. Cosmetics effective for both enlarged and sagging pores, which have different mechanisms of onset, have not been provided until now. The present invention's topical skin composition is the first to improve both enlarged and sagging pores. Consumers may not distinguish between sagging and enlarged pores, so cosmetics effective for both can provide a highly satisfying experience for those troubled by pores. 【0017】 The composition containing the active ingredients according to the present invention may be a cosmetic or a pharmaceutical. The concentration of the active ingredients according to the present invention can be appropriately determined according to their type and intended efficacy. The upper limit of the total concentration of the active ingredients according to the present invention can be selected from the viewpoint of the stability of the cosmetic, and may be 10% by mass, 7% by mass, 5% by mass, or 2% by mass. The lower limit of the total concentration of the active ingredients according to the present invention can be selected from the viewpoint of the effect of suppressing the appearance of pores, and may be 0.01% by mass, 0.1% by mass, or 0.5% by mass. 【0018】 The topical skin composition of the present invention is not particularly limited as long as it is applicable to the skin, and any dosage form can be applied, such as solution, emulsion, solid, semi-solid, powder, powder dispersion, water-oil two-layer separation, water-oil-powder three-layer separation, ointment, gel, aerosol, mousse, stick, etc. In addition to the active ingredient according to the present invention, the composition of the present invention may also contain penetration enhancers, moisturizers, thickeners, pH adjusters, bases, stabilizers, other active ingredients, excipients, emulsifiers, fragrances, etc., which are commonly used in topical skin preparations. 【0019】Such compositions may be cosmetics, pharmaceuticals, or quasi-drugs. When the composition is used as a cosmetic, it can be incorporated into facial or body cosmetics such as lotions, emulsions, serums, creams, packs, essences, and gels, as well as makeup cosmetics such as foundations, makeup bases, and concealers, and even bath additives. When incorporated into pharmaceuticals or quasi-drugs, it can be used as a topical skin preparation. Topical skin compositions can be administered over a long period of time. From the viewpoint of exhibiting an effect of improving the appearance of enlarged pores and / or blackheads, it may be administered for several days or more, one week or more, two weeks or more, one month or more, three months or more, or six months or more. There is no particular upper limit, but it may be several years or less, for example, one year or less. 【0020】 The skin to which the topical skin composition according to the present invention is applied may be any part of the skin, but from the viewpoint of exhibiting the effect of improving the appearance of pores, areas where pores are noticeable, such as the face, limbs, and abdomen, are preferred. It is desirable to apply it to the skin of subjects who are concerned about the appearance of pores, especially subjects who have sagging pores and / or enlarged pores. Among the face, areas such as the nose, cheeks, and forehead are particularly preferred. Since it can act on both sagging pores and enlarged pores, it can act on the entire face, but it is particularly preferable to apply it to areas such as the cheeks, forehead, nose, and around the nasolabial folds. 【0021】Another aspect of the present invention may relate to a cosmetic method comprising applying a topical skin composition containing retinol or a retinol derivative, glycylglycine, and tranexamic acid and / or a salt thereof to the skin, particularly the skin of the face. After application, a treatment to promote penetration, such as iontophoresis, may be applied. The cosmetic method is intended to treat, prevent, or improve incomplete keratinization, particularly pore care, and can exhibit a pore-improving effect, i.e., an effect of improving enlarged, noticeable, clogged, and / or blackheads of pores, and a pore-tightening effect. In yet another aspect, retinol or a retinol derivative, glycylglycine, and tranexamic acid and / or a salt thereof may be applied simultaneously or separately. The cosmetic method of the present invention may be performed by an individual or by a person other than a medical professional, such as an employee at a cosmetics store and a beauty provider such as a beauty salon. Therefore, the cosmetic method of the present invention is a non-therapeutic or non-medical method that can be distinguished from therapeutic or preventive methods performed by doctors or medical professionals, and is provided by a practitioner who is not a doctor or other medical professional. 【0022】 All references made herein are incorporated herein by reference in their entirety. The numerical ranges in this invention can be formed by any combination of upper and lower limits. 【0023】 The embodiments of the present invention described below are for illustrative purposes only and do not limit the technical scope of the invention. The technical scope of the invention is limited solely by the claims. Modifications to the invention, such as additions, deletions, and substitutions of constituent elements of the invention, can be made without departing from the spirit of the invention. 【0024】 Example 1: Preparation of the formulation A test cream containing retinol, glycylglycine, and tranexamic acid was prepared. Specifically, it was prepared based on the following formulation example. As a control, a placebo formulation without the active ingredients retinol, glycylglycine, and tranexamic acid was prepared and used for testing. 【0025】Example 2: Human Continuous Use Study 31 women aged 40-59 years were divided into two groups and each group received either 0.1 g of the test cream or a placebo on half of their face twice a day, morning and evening, for 8 weeks. Evaluations were conducted at 4 and 8 weeks from the start of application. Evaluations included replica solution, moisture content, sebum content, HSS analysis, self-assessment, and physician assessment. 【0026】 A skin replica was created according to the standard method of replica analysis. Specifically, a silicone agent was applied to create a replica that reproduced the unevenness of the skin surface, and photographs were taken of the replica using a confocal microscope. A predetermined area (3.3 mm) of the acquired image was examined. 2 The total pore area was measured (Figure 1A). Confocal micrographs of the same area from the same subject are shown (Figure 2A). After 4 weeks of continuous use of the test cream, the total pore area showed a decreasing trend, and after 8 weeks of continuous use of the test cream, the total pore area was significantly reduced compared to before use (paired t-test, p < 0.05). In addition, no change in total pore area was observed in the placebo group, and there was a significant difference in total pore area between the group that received placebo for 8 weeks and the group that used the test cream for 8 weeks (paired t-test, p < 0.05). 【0027】 Next, for the confocal microscope image of the replica, a predetermined area (3.3 mm) 2 The aspect ratio of the pores was measured for all pores (Figure 1B). Confocal micrographs of the same area from the same subject are shown (Figure 2B). With continuous use of the test cream for 4 weeks, the aspect ratio of the pores increased, and with continuous use of the test cream for 8 weeks, the aspect ratio of the pores increased further and became closer to circular. In addition, no change in the aspect ratio of the pores was observed in the placebo group. Significant differences in the aspect ratio of the pores were observed between the group that received placebo for 4 weeks and the group that received the test cream for 4 weeks, and between the group that received placebo for 8 weeks and the group that received the test cream for 8 weeks (4 weeks: paired t-test, p < 0.1, 8 weeks: paired t-test, p < 0.05). 【0028】The conductance of skin with measured moisture content was measured using a corneometer (multi-measurement instrument MPA580). The conductance ratio between the group treated with the test cream and the placebo group was calculated, and changes were examined at 4 and 8 weeks (Figure 3). The conductance ratio changed significantly between the pre-treatment group and the group that used the cream for 8 weeks (Bonferroni multiple comparison, p < 0.05). 【0029】 Sebum levels were measured using a Sebumeter (Courage + Khazaka electronic GmbH). The ratio of sebum levels after 4 weeks and 8 weeks of continuous use compared to pre-treatment levels was calculated for both the test cream group and the placebo group (Figure 4). Compared to the placebo group, the test cream group showed a significant decrease in sebum levels after 4 weeks (Wilcoxon's Signed rank test, p < 0.05). However, at 8 weeks, no significant difference in sebum levels was observed between the placebo group and the test cream group. 【0030】 Skin texture was measured using a handy skin sensor (HSS). In both the test cream group and the placebo group, the average skin texture score (lower scores indicate better texture) was calculated compared to before application, after 4 weeks of continuous use, and after 8 weeks of continuous use (Figure 5). The test cream group showed significantly greater improvement in skin texture at 4 and 8 weeks compared to the placebo group (Tukey-Kramer test, p < 0.05). 【0031】 Regarding pore size, self-assessment (by subjects) and physician assessment were performed using a common pore size grading table. In the group treated with the test cream, pore size was significantly smaller after 4 weeks and 8 weeks of continuous use (Figure 6A). In self-assessment, pore size was also smaller after 4 weeks and 8 weeks of continuous use in the same group treated with the test cream, but it was assessed as being even smaller than that assessed by physicians (Figure 6B) (Wilcoxon's Signed rank test, p < 0.05).

Claims

1. A topical skin composition comprising retinol or a retinol derivative, glycylglycine and / or a salt thereof, and tranexamic acid and / or a salt thereof.

2. 1.0IU / g ~ 5.0×10 5 The topical skin composition according to claim 1, comprising IU / g retinol or a retinol derivative, 0.05% to 3% by mass of glycylglycine and / or a salt thereof, and 0.1% to 2% by mass of tranexamic acid and / or a salt thereof.

3. The topical skin composition according to claim 1, wherein the retinol derivative is selected from the group consisting of retinoic acid or its salt, retinal, retinoid, and retinyl palmitate.

4. The topical skin composition according to claim 1, for use in improving the appearance of pores.

5. The topical skin composition according to claim 4, wherein the enlarged pores are caused by epidermal inflammation or incomplete keratinization.

6. The topical skin composition according to claim 5 for reducing the size of enlarged pores.

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