WO2023068090A1 - Agent for improving sagging pores - Google Patents

Agent for improving sagging pores Download PDF

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Publication number
WO2023068090A1
WO2023068090A1 PCT/JP2022/037698 JP2022037698W WO2023068090A1 WO 2023068090 A1 WO2023068090 A1 WO 2023068090A1 JP 2022037698 W JP2022037698 W JP 2022037698W WO 2023068090 A1 WO2023068090 A1 WO 2023068090A1
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WIPO (PCT)
Prior art keywords
sagging
pore
pores
skin
retinol
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PCT/JP2022/037698
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French (fr)
Japanese (ja)
Inventor
年以 飯田
豊 白杉
優希子 宮原
真帆 長谷川
美保 矢島
里香 中島
正廣 後明
徹 佐倉
孝一 吉野
正弘 大田
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株式会社 資生堂
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Priority to CN202280064253.8A priority Critical patent/CN117999062A/en
Priority to KR1020247009682A priority patent/KR20240087727A/en
Priority to JP2023554506A priority patent/JPWO2023068090A1/ja
Publication of WO2023068090A1 publication Critical patent/WO2023068090A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/67—Vitamins
    • A61K8/671—Vitamin A; Derivatives thereof, e.g. ester of vitamin A acid, ester of retinol, retinol, retinal
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/007—Preparations for dry skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/08—Anti-ageing preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/592—Mixtures of compounds complementing their respective functions

Definitions

  • the present disclosure relates to a sagging pore improving agent, more specifically, a sagging pore improving agent containing glycylglycine and retinol, and a cosmetic method using the same.
  • astringent lotions are intended to tighten the skin, and alcohol temporarily lowers the skin surface temperature, and organic acids and the like act to coagulate proteins. Therefore, since it temporarily tightens the skin, the load on the skin is large, and it is not a fundamental solution to conspicuous pores, and the effect is not sufficient.
  • Patent Document 1 discloses glycine derivatives, aminodicarboxylic acid derivatives, acylaminodicarboxylic acid derivatives, pyrrolidinecarboxylic acid derivatives, piperidinecarboxylic acid derivatives, and hexamethyleneiminecarboxylic acid.
  • Parakeratosis inhibitors and pore shrinking agents comprising one or more compounds selected from the group consisting of derivatives, ⁇ -alanine derivatives and salts of the above derivatives are disclosed.
  • One object of the present disclosure is to provide a sagging pore improving agent, more specifically, a sagging pore improving agent containing glycylglycine and retinol, and to provide a cosmetic method using the same. .
  • the present inventors conducted extensive research to identify ingredients that improve sagging pores, and found for the first time that a combination of glycylglycine and retinol is particularly effective in improving sagging pores. Then, a sagging pore improving agent and a cosmetic or non-therapeutic method for improving sagging pores, characterized by containing glycylglycine and retinol, were developed.
  • a sagging pore improving agent containing glycylglycine and retinol A sagging pore improving agent containing glycylglycine and retinol.
  • Aspect 2 The agent for improving sagging pores according to Aspect 1, containing 0.5% or more and 2.0% or less of glycylglycine.
  • Aspect 3 The sagging pore improving agent according to Aspect 1 or 2, which contains 0.3 ⁇ 10 2 IU/g or more and 1.0 ⁇ 10 5 IU/g or less of retinol.
  • Aspect 4 The sagging pore improving agent according to any one of aspects 1 to 3, which improves the aspect ratio of the pore shape.
  • a cosmetic method comprising the step of applying the agent for improving sagging pores according to any one of aspects 1 to 8 or the external preparation for skin according to aspect 9 to the skin of a subject.
  • a wrinkle reducing agent comprising glycylglycine and retinol.
  • a skin elasticity improving agent containing glycylglycine and retinol.
  • a skin moisturizing agent containing glycylglycine and retinol.
  • sagging pores and the like can be improved by applying a composition containing a combination of glycylglycine and retinol as active ingredients to the skin.
  • FIG. 1 is a graph showing changes in pore aspect ratio caused by application of the test formulations over a period of 12 weeks.
  • FIG. 2 is a graph showing the change in pore area (total pore area) caused by application of the test formulation over 12 weeks.
  • FIG. 3 is a graph showing the change in pore score caused by application of the test formulation over 12 weeks.
  • FIG. 4 is a graph showing changes in water content (corneometer readings) caused by application of the test formulations over a period of 12 weeks.
  • FIG. 5 is a graph showing the change in softness (R0: Uf (maximum suction height)) produced by application of the test formulation over a period of 12 weeks.
  • R0 Uf (maximum suction height
  • FIG. 6 is a graph showing changes in elasticity (R5: Ur/Ue (instantaneous return after release of negative pressure/instantaneous deformation upon suction)) produced by application of the test formulation over a 12-week period.
  • FIG. 7 is a graph showing changes in questionnaire results caused by application of the test formulation over 12 weeks.
  • the sagging pore improving agent contains glycylglycine and retinol as active ingredients.
  • one embodiment of the present disclosure relates to a composition for improving sagging pores, which contains glycylglycine and retinol as active ingredients.
  • one aspect of the present disclosure relates to the use of a combination of glycylglycine and retinol in the manufacture of a pharmaceutical or cosmetic product for use in improving sagging pores.
  • sagging pores refers to pores that are oval in shape. Sagging pores are tears-shaped (elliptical) pores due to sagging (decreased elasticity) of the cheeks and face line, which mainly occurs after the age of 40. In sagging pores, minor/major axis values of less than 1, especially less than 0.6, appear sagging. In addition, sagging pores are conspicuously seen on both cheeks in human facial skin.
  • Glycylglycine is a glycine dipeptide represented by the chemical formula NH 2 CH 2 CONHCH 2 COOH, and is one of peptides with a simple structure. Glycylglycine is commercially available in high purity and readily available.
  • the agent for improving sagging pores preferably contains 0.05% or more and 3.0% or less, more preferably 0.5% or more and 2.0% or less, of glycylglycine.
  • the percentage (%) in this specification refers to % by mass unless otherwise specified.
  • Retinol is one of the fat-soluble vitamins represented by the chemical formula C20H30O , and is also known as vitamin A1. High-purity products are commercially available and readily available.
  • the sagging pore improvement agent preferably contains retinol in an amount of 1.0 IU/g or more and 5 ⁇ 10 5 IU/g or less, and 0.3 ⁇ 10 2 IU/g or more and 1.0 ⁇ 10 5 IU/g.
  • IU stands for international unit.
  • the sagging pore improver according to the present disclosure is used as a composition to improve the aspect ratio of pore shape.
  • the aspect ratio is defined as "minor axis/major axis", and when the value increases and approaches 1 (e.g., when the aspect ratio value changes from 0.6 to 0.7 ), and the aspect ratio is evaluated as improved.
  • improvement of sagging pores means that the shape of the pores becomes closer to a perfect circle.
  • the shape and size of pores can be evaluated, for example, by a three-dimensional measurement method for pores as described in Japanese Patent No. 4286724.
  • the sagging pore improver according to the present disclosure is used as a composition for reducing pore size.
  • a composition for reducing pore size For example, when the length of the slack pore in the longitudinal direction is reduced, the size of the pore is reduced and the aspect ratio of the pore is improved.
  • the pore size can also be evaluated, for example, by image analysis using a skin image diagnostic device (eg, Visia Evolution manufactured by Canfield Scientific).
  • Pores can be evaluated, as described above, by a three-dimensional measurement method for pores that enables precise measurement of the three-dimensional shape of pores, for example, as described in Japanese Patent No. 4286724. Briefly, first, a replica of the skin surface condition is collected and measured using a confocal microscope to obtain three-dimensional shape measurement data of the replica. Next, correction processing such as noise removal is performed, and then processing for extracting pores from the noise-removed data is performed. Next, processing may be performed to remove information about the texture of the skin in the pore portion from the extracted pore data. Then, pore evaluation can be performed based on the pore 3D analysis data obtained as described above.
  • Pores can also be evaluated by image analysis using a skin image diagnostic device (eg, Visia Evolution manufactured by Canfield Scientific, etc.), as described above.
  • a skin image diagnostic device eg, Visia Evolution manufactured by Canfield Scientific, etc.
  • the sagging pore improver according to the present disclosure is used as a composition for improving wrinkles.
  • a composition for use in improving wrinkles comprising glycylglycine and retinol as active ingredients.
  • one aspect of the present disclosure also relates to anti-wrinkle agents comprising glycylglycine and retinol.
  • one aspect of the present disclosure relates to the use of a combination of glycylglycine and retinol in the manufacture of a medicament or cosmetic for use in improving wrinkles.
  • the evaluation of wrinkles can be performed, for example, by image analysis using a skin image diagnostic device (eg, Visia Evolution manufactured by Canfield Scientific), observation by a skilled person, and visual judgment.
  • the sagging pore improver according to the present disclosure is used as a composition for improving skin elasticity.
  • a composition for use in improving firmness comprising glycylglycine and retinol as active ingredients. That is, one aspect of the present disclosure also relates to a skin elasticity improving agent containing glycylglycine and retinol. From another aspect, one aspect of the present disclosure relates to the use of a combination of glycylglycine and retinol in the manufacture of a pharmaceutical or cosmetic product for use in improving firmness.
  • the elasticity of the skin can be evaluated, for example, by measuring the viscoelasticity of the skin using a commercially available device (for example, Cutometer manufactured by Courage+Khazaka).
  • the sagging pore improver according to the present disclosure is used as a composition for improving skin moisturization.
  • a composition for use in improving skin moisturization comprising glycylglycine and retinol as active ingredients. That is, one aspect of the present disclosure also relates to a skin moisturizing agent containing glycylglycine and retinol. From another aspect, one aspect of the present disclosure relates to the use of a combination of glycylglycine and retinol in the manufacture of a medicament or cosmetic for use in improving skin moisturization.
  • the moisturizing property of the skin can be evaluated, for example, by measuring the moisture content of the stratum corneum using a commercially available device (eg, Corneometer manufactured by Courage+Khazaka).
  • the present invention relates to an external skin preparation comprising a sagging pore improving agent according to the present disclosure.
  • the topical skin preparation can be prepared as a cosmetic, quasi-drug, or pharmaceutical.
  • Cosmetics can be sunscreens, lotions, serums, beauty creams, aftercare lotions, sun oils, etc., but can be any cosmetics as long as they are applied to the skin.
  • external skin preparations include external solids, external powders, external liquids, liniments, sprays, external aerosols, pump sprays, ointments, creams, gels, patches, tapes, poultices, etc. It can be prepared in any form.
  • the sagging pore improving agent or skin preparation for external use according to the present disclosure can be appropriately blended with arbitrary compounding ingredients used in cosmetics, pharmaceuticals, etc., as necessary, as long as the effects are not impaired.
  • the optional ingredients include oils, surfactants, powders, colorants, water, alcohols, thickeners, chelating agents, silicones, antioxidants, UV absorbers, moisturizers, fragrances, and various medicinal effects.
  • Other ingredients may include, for example, other anti-inflammatory ingredients, whitening ingredients, and the like.
  • creams contain, in addition to glycylglycine and retinol, water, alcohol, humectants, thickeners, film-forming agents, activators, oils, stabilizers, percutaneous absorption inhibitors, coloring agents, chelating agents, Buffers, preservatives, flavoring agents and the like may be included.
  • the present invention relates to a cosmetic or non-therapeutic method comprising applying a sagging pore improving agent according to the present disclosure, a topical skin preparation according to the present disclosure to the skin of a subject.
  • the subject can be a mammal, but is preferably human.
  • the sagging pore improving agent or skin external preparation disclosed herein improves sagging pores, improves the aspect ratio of the pore shape, reduces the pore size, improves wrinkles, It can be used in cosmetic or non-therapeutic methods to improve skin elasticity or to improve skin moisturization.
  • the external preparation for skin is applied to the site where the desired effect is desired, such as the face, neck, hands, arms, legs, and the like.
  • Application can be in any manner, including application by hand, applicator, and the like.
  • the number, frequency, amount, etc., of application are appropriately set according to the desired effect and the like.
  • the cosmetic or non-therapeutic method according to the present disclosure does not include so-called medical practice.
  • one aspect of the present disclosure is to improve sagging pores, improve aspect ratio of pore shape, reduce pore size, improve wrinkles, improve skin elasticity. , or the use of a combination of glycylglycine and retinol to improve skin moisturization.
  • the data disclosed herein demonstrate that application of a composition comprising a combination of glycylglycine and retinol to the skin improves sagging pores leading to improved skin elasticity, moisture retention and wrinkles. showing.
  • compositions containing a combination of glycylglycine and retinol can be used to prepare topical skin preparations and other compositions for use in improving sagging pores and the like.
  • one aspect of the present disclosure is to improve sagging pores, to improve the aspect ratio of the shape of pores, to reduce the size of pores, to improve wrinkles, to improve skin elasticity. , or the use of a combination of glycylglycine and retinol in the preparation of a topical skin preparation for improving skin moisturization.
  • Example 1 Outline of continuous use effect test of cream containing glycylglycine + retinol (purpose) For the purpose of "improving sagging pores", for which no active ingredients existed so far, we conducted a continuous use effect test of a cream containing glycylglycine and retinol. (Method) A glycylglycine + retinol combination cream expected to be effective for sagging pores was applied to 19 subjects for 12 weeks, and pore shape and skin parameters were evaluated. The cream used contained 1.6% glycylglycine and 0.2 ⁇ 10 4 IU/g retinol.
  • the amount to be used at one time was 0.2 g (0.1 g for each of the left and right cheeks), and was used once in the morning and once at night. (result)
  • VISIA cheek replicas and skin imaging diagnostic equipment
  • the application of the test formulation significantly improved the degree of sagging of pores (aspect ratio) and significantly reduced the area of some pores.
  • the moisture content of the stratum corneum increased, the elasticity increased, and the skin condition improved.
  • Example 2 Test Protocol (Subjects) A test was conducted on 19 males and females (14 females, 5 males, 51.1 ⁇ 5.7 years old) (mean ⁇ SD) suffering from sagging pores in their 40s and above. (Continuous use period) A cream formulation containing 1.6% glycylglycine and 0.2 ⁇ 10 4 IU/g retinol was continuously applied to both cheeks for 12 weeks (measurements were taken after 0, 4, 8 and 12 weeks). (Measurement item) Measurement items included the degree and size of pore sagging (replica), stratum corneum water content, viscoelasticity (elasticity, softness), appearance image, and the like. In the evaluation of pores using a replica, as described in Japanese Patent No.
  • a replica of the skin surface condition is collected and measured using a confocal microscope to obtain three-dimensional shape measurement data of the replica.
  • SILFLO Amic Group
  • the moisture content and viscoelasticity (elasticity, softness) of the stratum corneum can be measured by commercially available instruments such as Corneometer (CM825) and Cutometer (MPA580). ,It was measured).
  • Commercially available equipment such as VISIA Evolution can be used to analyze appearance images.
  • the significance test of the measured values was performed using the paired t-test when the measured values followed the normal distribution, and using the Wilcoxon signed rank test when the measured values did not follow the normal distribution. 05.
  • Example 4 Results of Analysis from VISIA Images As a result of analysis of appearance images obtained with VISIA, as shown in Table 1 and FIG. . These results demonstrate that a composition comprising glycylglycine and retinol can be used for pore size reduction and wrinkle improvement.
  • Example 5 Results of Analysis of Measuring Instrument Data
  • Table 2 results of analysis of stratum corneum moisture content, softness, and elasticity obtained with the measuring instrument are shown in Table 2 below and FIGS. , there was a significant improvement or trend towards improvement in resilience ( * represents p ⁇ 0.05, ** p ⁇ 0.01, *** represents p ⁇ 0.001 significance level).
  • Example 6 Results of Questionnaire to Subjects As shown in FIG. 7, the results of a questionnaire to the subjects also showed that the pores tended to improve.
  • the stacked graph on the left side of FIG. 7 shows that the total of the responses to the questionnaire item “Pores are less noticeable” exceeds 80% after 12 weeks, with the total of “I think so” and “I think so”. there is
  • the graph on the right shows the results of quantifying the responses and analyzing the averages. From this graph as well, it can be seen that the feeling that pores have become less noticeable has increased significantly.

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Abstract

The present disclosure pertains to: an agent for improving sagging pores and the like; and a beautification method, a non-therapeutic method, or the like that uses said agent. More specifically, it is possible to prepare an agent for improving sagging pores and the like by adopting a combination of glycylglycine and retinol, and to use the agent in a beautification method or a non-therapeutic method for improving sagging pores.

Description

たるみ毛穴改善剤Sagging pore improver
　本開示は、たるみ毛穴の改善剤、より詳細には、グリシルグリシンとレチノールを含む、たるみ毛穴の改善剤、ならびにそれを用いた美容方法に関する。 The present disclosure relates to a sagging pore improving agent, more specifically, a sagging pore improving agent containing glycylglycine and retinol, and a cosmetic method using the same.
　近年、毛穴の目立ちに対する悩みは大きくなっており、これを改善する皮膚外用組成物が必要とされてきた。しかし毛穴が目立つメカニズムは明らかではなく、収斂化粧水や角栓の除去による対応が一般的である。あるいはファンデーションで見た目の改善を図ることも多い。 In recent years, concerns about conspicuous pores have increased, and there has been a need for external skin compositions that improve this. However, the mechanism by which pores are conspicuous is not clear, and the common treatment is to use an astringent lotion or remove keratotic plugs. Or they often use foundation to improve their appearance.
　しかし、例えば収斂化粧水は、肌を引き締めることを目的にしており、アルコールにより一時的に皮膚表面温度を下げたり、有機酸等により、蛋白質を凝固させたりする作用による。従って一時的に肌を引き締めるものであるため、皮膚への負荷が大きく、また毛穴の目立ちの根本的な解決となっておらず、その効果も充分ではなかった。 However, for example, astringent lotions are intended to tighten the skin, and alcohol temporarily lowers the skin surface temperature, and organic acids and the like act to coagulate proteins. Therefore, since it temporarily tightens the skin, the load on the skin is large, and it is not a fundamental solution to conspicuous pores, and the effect is not sufficient.
　毛穴の目立ちを改善する皮膚外用組成物の一つとして、特許文献１には、グリシン誘導体、アミノジカルボン酸誘導体、アシルアミノジカルボン酸誘導体、ピロリジンカルボン酸誘導体、ピペリジンカルボン酸誘導体、ヘキサメチレンイミンカルボン酸誘導体およびβ－アラニン誘導体並びに前記各誘導体の塩からなる群から選ばれる化合物の１種または２種以上からなる不全角化抑制剤、毛穴縮小剤が開示されている。 As one of external skin compositions for improving the conspicuity of pores, Patent Document 1 discloses glycine derivatives, aminodicarboxylic acid derivatives, acylaminodicarboxylic acid derivatives, pyrrolidinecarboxylic acid derivatives, piperidinecarboxylic acid derivatives, and hexamethyleneiminecarboxylic acid. Parakeratosis inhibitors and pore shrinking agents comprising one or more compounds selected from the group consisting of derivatives, β-alanine derivatives and salts of the above derivatives are disclosed.
　一方で、加齢とともに生じる「たるみ毛穴」については、これまでケア成分の開発には至っていなかった。 On the other hand, no care ingredients have been developed for "sagging pores" that occur with aging.
特許第５２４１０５８号Patent No. 5241058
　本開示は、たるみ毛穴の改善剤、より詳細には、グリシルグリシンとレチノールを含む、たるみ毛穴の改善剤を提供すること、ならびにそれを用いた美容方法を提供することを目的の一つとする。 One object of the present disclosure is to provide a sagging pore improving agent, more specifically, a sagging pore improving agent containing glycylglycine and retinol, and to provide a cosmetic method using the same. .
　本発明者らは、たるみ毛穴を改善する成分を同定すべく鋭意研究を行ったところ、グリシルグリシンとレチノールの組み合わせが、たるみ毛穴の改善に特に有効であることをはじめて見出した。そして、グリシルグリシンとレチノールを含有することを特徴とする、たるみ毛穴改善剤、およびたるみ毛穴を改善するための美容または非治療的方法を開発した。 The present inventors conducted extensive research to identify ingredients that improve sagging pores, and found for the first time that a combination of glycylglycine and retinol is particularly effective in improving sagging pores. Then, a sagging pore improving agent and a cosmetic or non-therapeutic method for improving sagging pores, characterized by containing glycylglycine and retinol, were developed.
　そこで、本開示は以下の態様に関する：
［態様１］グリシルグリシンとレチノールを含む、たるみ毛穴改善剤。
［態様２］グリシルグリシンを０．５％以上２．０％以下含む、態様１記載のたるみ毛穴改善剤。
［態様３］レチノールを０．３×１０２ＩＵ／g以上１．０×１０５ＩＵ／ｇ以下含む、態様１または２記載のたるみ毛穴改善剤。
［態様４］毛穴の形状の縦横比を改善する、態様１～３のいずれか一項記載のたるみ毛穴改善剤。
［態様５］毛穴の大きさを縮小させる、態様１～４のいずれか一項記載のたるみ毛穴改善剤。
［態様６］シワを改善する、態様１～５のいずれか一項記載のたるみ毛穴改善剤。
［態様７］肌の弾力を改善する、態様１～６のいずれか一項記載のたるみ毛穴改善剤。
［態様８］肌の保湿性を改善する、態様１～７のいずれか一項記載のたるみ毛穴改善剤。
［態様９］態様１～８のいずれか一項記載のたるみ毛穴改善剤を含む皮膚外用剤。
［態様１０］態様１～８のいずれか一項記載のたるみ毛穴改善剤または態様９記載の皮膚外用剤を対象の皮膚に適用する工程を含む、美容方法。
［態様１１］
　グリシルグリシンとレチノールを含む、シワ改善剤。
［態様１２］
　グリシルグリシンとレチノールを含む、肌弾力改善剤。
［態様１３］
　グリシルグリシンとレチノールを含む、肌保湿性改善剤。 Accordingly, the present disclosure is directed to the following aspects:
[Aspect 1] A sagging pore improving agent containing glycylglycine and retinol.
[Aspect 2] The agent for improving sagging pores according to Aspect 1, containing 0.5% or more and 2.0% or less of glycylglycine.
[Aspect 3] The sagging pore improving agent according to Aspect 1 or 2, which contains 0.3×10 2 IU/g or more and 1.0×10 5 IU/g or less of retinol.
[Aspect 4] The sagging pore improving agent according to any one of aspects 1 to 3, which improves the aspect ratio of the pore shape.
[Aspect 5] The sagging pore improving agent according to any one of aspects 1 to 4, which reduces the size of pores.
[Aspect 6] The sagging pore improving agent according to any one of aspects 1 to 5, which improves wrinkles.
[Aspect 7] The sagging pore improving agent according to any one of aspects 1 to 6, which improves skin elasticity.
[Aspect 8] The agent for improving sagging pores according to any one of Aspects 1 to 7, which improves moisturizing properties of the skin.
[Aspect 9] An external skin preparation comprising the agent for improving sagging pores according to any one of Aspects 1 to 8.
[Aspect 10] A cosmetic method comprising the step of applying the agent for improving sagging pores according to any one of aspects 1 to 8 or the external preparation for skin according to aspect 9 to the skin of a subject.
[Aspect 11]
A wrinkle reducing agent comprising glycylglycine and retinol.
[Aspect 12]
A skin elasticity improving agent containing glycylglycine and retinol.
[Aspect 13]
A skin moisturizing agent containing glycylglycine and retinol.
　本開示によれば、グリシルグリシンとレチノールの組み合わせを有効成分する組成物を皮膚に適用することで、たるみ毛穴等を改善することができる。 According to the present disclosure, sagging pores and the like can be improved by applying a composition containing a combination of glycylglycine and retinol as active ingredients to the skin.
図１は、１２週間にわたる試験製剤の適用により生じた毛穴縦横比の変化を示すグラフである。FIG. 1 is a graph showing changes in pore aspect ratio caused by application of the test formulations over a period of 12 weeks. 図２は、１２週間にわたる試験製剤の適用により生じた毛穴面積（毛穴総面積）の変化を示すグラフである。FIG. 2 is a graph showing the change in pore area (total pore area) caused by application of the test formulation over 12 weeks. 図３は、１２週間にわたる試験製剤の適用により生じた毛穴スコアの変化を示すグラフである。FIG. 3 is a graph showing the change in pore score caused by application of the test formulation over 12 weeks. 図４は、１２週間にわたる試験製剤の適用により生じた水分量（コルネオメーター値）の変化を示すグラフである。FIG. 4 is a graph showing changes in water content (corneometer readings) caused by application of the test formulations over a period of 12 weeks. 図５は、１２週間にわたる試験製剤の適用により生じた柔らかさ（Ｒ０：Ｕｆ（最大吸引高））の変化を示すグラフである。FIG. 5 is a graph showing the change in softness (R0: Uf (maximum suction height)) produced by application of the test formulation over a period of 12 weeks. 図６は、１２週間にわたる試験製剤の適用により生じた弾性（Ｒ５：Ｕｒ／Ｕｅ（陰圧解除後の瞬時の戻り／吸引時の瞬時の変形））の変化を示すグラフである。FIG. 6 is a graph showing changes in elasticity (R5: Ur/Ue (instantaneous return after release of negative pressure/instantaneous deformation upon suction)) produced by application of the test formulation over a 12-week period. 図７は、１２週間にわたる試験製剤の適用により生じたアンケート結果の変化を示すグラフである。FIG. 7 is a graph showing changes in questionnaire results caused by application of the test formulation over 12 weeks.
（たるみ毛穴改善剤）
　本開示の一つの態様において、本開示に従うたるみ毛穴改善剤は、グリシルグリシンとレチノールを有効成分として含む。別の観点からは、本開示の一つの態様は、グリシルグリシンとレチノールを有効成分として含む、たるみ毛穴の改善に用いるための組成物に関する。さらに別の観点からは、本開示の一つの態様は、たるみ毛穴の改善に用いるための薬剤または化粧品の製造における、グリシルグリシンとレチノールの組み合わせの使用に関する。 (Sagging pore improvement agent)
In one aspect of the present disclosure, the sagging pore improving agent according to the present disclosure contains glycylglycine and retinol as active ingredients. From another point of view, one embodiment of the present disclosure relates to a composition for improving sagging pores, which contains glycylglycine and retinol as active ingredients. From yet another aspect, one aspect of the present disclosure relates to the use of a combination of glycylglycine and retinol in the manufacture of a pharmaceutical or cosmetic product for use in improving sagging pores.
　本明細書において用いる場合、「たるみ毛穴」という用語は、形状が楕円形となっている毛穴を指す。たるみ毛穴は、主に４０代以降に生じる、頬やフェイスラインのたるみ（弾力低下）によって、形状が涙形（楕円形）となった毛穴である。たるみ毛穴において、短軸／長軸の値は１未満であり、特に０．６未満だとたるんで見える。またたるみ毛穴は、人の顔の肌では両頬に顕著に見られる。 As used herein, the term "sagging pores" refers to pores that are oval in shape. Sagging pores are tears-shaped (elliptical) pores due to sagging (decreased elasticity) of the cheeks and face line, which mainly occurs after the age of 40. In sagging pores, minor/major axis values of less than 1, especially less than 0.6, appear sagging. In addition, sagging pores are conspicuously seen on both cheeks in human facial skin.
（グリシルグリシン）
　グリシルグリシン（Glycylglycine）は、化学式ＮＨ２ＣＨ２ＣＯＮＨＣＨ２ＣＯＯＨで表されるグリシンのジペプチドであり、単純な構造のペプチドの一つである。グリシルグリシンは、高純度のものが市販されており、容易に入手可能である。 (glycylglycine)
Glycylglycine is a glycine dipeptide represented by the chemical formula NH 2 CH 2 CONHCH 2 COOH, and is one of peptides with a simple structure. Glycylglycine is commercially available in high purity and readily available.
　一部の態様において、たるみ毛穴改善剤は、グリシルグリシンを０．０５%以上３．０%以下含むことが好ましく、０．５％以上２．０％以下がより好ましい。なお、本明細書において百分率（％）は特に明記しない限り、質量％を指す。 In some aspects, the agent for improving sagging pores preferably contains 0.05% or more and 3.0% or less, more preferably 0.5% or more and 2.0% or less, of glycylglycine. In addition, the percentage (%) in this specification refers to % by mass unless otherwise specified.
（レチノール）
　レチノールは、化学式 Ｃ２０Ｈ３０Ｏで表される脂溶性ビタミンの一つで、ビタミンＡ１としても知られる。高純度のものが市販されており、容易に入手可能である。 (retinol)
Retinol is one of the fat-soluble vitamins represented by the chemical formula C20H30O , and is also known as vitamin A1. High-purity products are commercially available and readily available.
　一部の態様において、たるみ毛穴改善剤は、レチノールを１．０ＩＵ／ｇ以上、５ｘ１０５ＩＵ／ｇ以下含むことが好ましく、０．３×１０２ＩＵ／ｇ以上、１．０ｘ１０５ＩＵ／ｇ以下がより好ましい。なお、ここでＩＵは国際単位（international unit）を表す。 In some aspects, the sagging pore improvement agent preferably contains retinol in an amount of 1.0 IU/g or more and 5×10 5 IU/g or less, and 0.3×10 2 IU/g or more and 1.0×10 5 IU/g. The following are more preferred. Here, IU stands for international unit.
（毛穴の形状および大きさ）
　一つの態様において、本開示に従うたるみ毛穴改善剤は、毛穴の形状の縦横比を改善するための組成物として使用される。本開示の文脈において、縦横比は「短軸／長軸」として定義され、値が増加して１に近づく場合（例えば、縦横比の値が０．６から０．７に変化したような場合）、縦横比が改善したと評価される。つまり、たるみ毛穴が改善されるとは、毛穴の形状が、より正円に近づくことを言う。なお、毛穴の形状や大きさは、例えば、特許第４２８６７２４号に記載されるような、毛穴の三次元測定方法により評価することができる。 (Pore shape and size)
In one embodiment, the sagging pore improver according to the present disclosure is used as a composition to improve the aspect ratio of pore shape. In the context of this disclosure, the aspect ratio is defined as "minor axis/major axis", and when the value increases and approaches 1 (e.g., when the aspect ratio value changes from 0.6 to 0.7 ), and the aspect ratio is evaluated as improved. In other words, improvement of sagging pores means that the shape of the pores becomes closer to a perfect circle. The shape and size of pores can be evaluated, for example, by a three-dimensional measurement method for pores as described in Japanese Patent No. 4286724.
　一つの態様において、本開示に従うたるみ毛穴改善剤は、毛穴の大きさを縮小させるための組成物として使用される。例えば、たるみ毛穴の長軸方向の長さが小さくなった場合には、毛穴の大きさが縮小するとともに、毛穴の縦横比が改善される。なお、毛穴の大きさは、例えば、肌画像診断装置（例えば、Canfield Scientific社製Visia Evolutionなど）を用いた画像解析によっても評価することができる。 In one embodiment, the sagging pore improver according to the present disclosure is used as a composition for reducing pore size. For example, when the length of the slack pore in the longitudinal direction is reduced, the size of the pore is reduced and the aspect ratio of the pore is improved. The pore size can also be evaluated, for example, by image analysis using a skin image diagnostic device (eg, Visia Evolution manufactured by Canfield Scientific).
　毛穴の評価は、上述のように、例えば、特許第４２８６７２４号に記載されるような、毛穴の立体的形状を精密に計測することを可能とする毛穴の三次元測定方法により行うことができる。簡単に説明すると、まず、皮膚表面状態を採取したレプリカを採取し、共焦点顕微鏡を用いてこれを計測することによりレプリカの三次元形状計測データを求める。次に、ノイズ除去等の補正処理を実施し、その上でこのノイズ除去データから毛穴を抽出する処理を行なう。次に、毛穴を抽出されたデータから、毛穴部分における肌のキメに関する情報を除去する処理を行なってもよい。そして、上記のようにして得られた毛穴３Ｄ解析データに基づき、毛穴評価を行なうことができる。 Pores can be evaluated, as described above, by a three-dimensional measurement method for pores that enables precise measurement of the three-dimensional shape of pores, for example, as described in Japanese Patent No. 4286724. Briefly, first, a replica of the skin surface condition is collected and measured using a confocal microscope to obtain three-dimensional shape measurement data of the replica. Next, correction processing such as noise removal is performed, and then processing for extracting pores from the noise-removed data is performed. Next, processing may be performed to remove information about the texture of the skin in the pore portion from the extracted pore data. Then, pore evaluation can be performed based on the pore 3D analysis data obtained as described above.
　毛穴の評価は、上述のように、肌画像診断装置（例えば、Canfield Scientific社製Visia Evolutionなど）を用いた画像解析により行うこともできる。 Pores can also be evaluated by image analysis using a skin image diagnostic device (eg, Visia Evolution manufactured by Canfield Scientific, etc.), as described above.
（シワの改善）
　一つの態様において、本開示に従うたるみ毛穴改善剤は、シワを改善するための組成物として使用される。よって、本開示の一つの態様は、グリシルグリシンとレチノールを有効成分として含む、シワの改善に用いるための組成物に関する。すなわち、本開示の一つの態様は、グリシルグリシンとレチノールを含む、シワ改善剤にも関する。また、別の観点からは、本開示の一つの態様は、シワの改善に用いるための薬剤または化粧品の製造における、グリシルグリシンとレチノールの組み合わせの使用に関する。なお、シワの評価は、例えば、肌画像診断装置（例えば、Canfield Scientific社製Visia Evolutionなど）を用いた画像解析や、熟練者による観察、視覚判定により行うことができる。 (improvement of wrinkles)
In one embodiment, the sagging pore improver according to the present disclosure is used as a composition for improving wrinkles. Accordingly, one aspect of the present disclosure relates to a composition for use in improving wrinkles, comprising glycylglycine and retinol as active ingredients. Thus, one aspect of the present disclosure also relates to anti-wrinkle agents comprising glycylglycine and retinol. From another aspect, one aspect of the present disclosure relates to the use of a combination of glycylglycine and retinol in the manufacture of a medicament or cosmetic for use in improving wrinkles. The evaluation of wrinkles can be performed, for example, by image analysis using a skin image diagnostic device (eg, Visia Evolution manufactured by Canfield Scientific), observation by a skilled person, and visual judgment.
（弾力またはハリの改善）
　一つの態様において、本開示に従うたるみ毛穴改善剤は、肌の弾力（ハリ）を改善するための組成物として使用される。よって、本開示の一つの態様は、グリシルグリシンとレチノールを有効成分として含む、弾力（ハリ）の改善に用いるための組成物に関する。すなわち、本開示の一つの態様は、グリシルグリシンとレチノールを含む、肌弾力改善剤にも関する。また、別の観点からは、本開示の一つの態様は、弾力（ハリ）の改善に用いるための薬剤または化粧品の製造における、グリシルグリシンとレチノールの組み合わせの使用に関する。なお、肌の弾力は、例えば、市販の機器（例えば、Courage+Khazaka社製　Cutometerなど）を用いて皮膚の粘弾性測定を測定することにより評価することができる。 (improved elasticity or firmness)
In one embodiment, the sagging pore improver according to the present disclosure is used as a composition for improving skin elasticity. Accordingly, one aspect of the present disclosure relates to a composition for use in improving firmness comprising glycylglycine and retinol as active ingredients. That is, one aspect of the present disclosure also relates to a skin elasticity improving agent containing glycylglycine and retinol. From another aspect, one aspect of the present disclosure relates to the use of a combination of glycylglycine and retinol in the manufacture of a pharmaceutical or cosmetic product for use in improving firmness. The elasticity of the skin can be evaluated, for example, by measuring the viscoelasticity of the skin using a commercially available device (for example, Cutometer manufactured by Courage+Khazaka).
（保湿性の改善）
　一つの態様において、本開示に従うたるみ毛穴改善剤は、肌の保湿性を改善するための組成物として使用される。よって、本開示の一つの態様は、グリシルグリシンとレチノールを有効成分として含む、肌の保湿性の改善に用いるための組成物に関する。すなわち、本開示の一つの態様は、グリシルグリシンとレチノールを含む、肌保湿性改善剤にも関する。また、別の観点からは、本開示の一つの態様は、肌の保湿性の改善に用いるための薬剤または化粧品の製造における、グリシルグリシンとレチノールの組み合わせの使用に関する。なお、肌の保湿性は、例えば、市販の機器（例えば、Courage+Khazaka社製Corneometerなど）を用いて角層水分量を測定することにより評価することができる。 (Improved moisturizing properties)
In one embodiment, the sagging pore improver according to the present disclosure is used as a composition for improving skin moisturization. Accordingly, one aspect of the present disclosure relates to a composition for use in improving skin moisturization, comprising glycylglycine and retinol as active ingredients. That is, one aspect of the present disclosure also relates to a skin moisturizing agent containing glycylglycine and retinol. From another aspect, one aspect of the present disclosure relates to the use of a combination of glycylglycine and retinol in the manufacture of a medicament or cosmetic for use in improving skin moisturization. The moisturizing property of the skin can be evaluated, for example, by measuring the moisture content of the stratum corneum using a commercially available device (eg, Corneometer manufactured by Courage+Khazaka).
（皮膚外用剤）
　一つの態様において、本発明は、本開示に従うたるみ毛穴改善剤を含む皮膚外用剤に関する。一部の態様において、皮膚外用剤は、化粧品、医薬部外品、または医薬品として調製されうる。化粧品は、日焼け止め、化粧水、美容液、美容クリーム、アフターケアローション、サンオイルなどでありうるが、皮膚に適用されるものであれば任意の化粧品でありうる。 (External preparation for skin)
In one aspect, the present invention relates to an external skin preparation comprising a sagging pore improving agent according to the present disclosure. In some aspects, the topical skin preparation can be prepared as a cosmetic, quasi-drug, or pharmaceutical. Cosmetics can be sunscreens, lotions, serums, beauty creams, aftercare lotions, sun oils, etc., but can be any cosmetics as long as they are applied to the skin.
　かかる皮膚外用剤には、グリシルグリシンとレチノールに加えて、化粧品や医薬品等に用いられる任意配合成分を、必要に応じて適宜配合することができる。また、皮膚外用剤は、外用固形剤、外用散剤、外用液剤、リニメント剤、スプレー剤、外用エアゾール剤、ポンプスプレー剤、軟膏剤、クリーム剤、ゲル剤、貼付剤、テープ剤、パップ剤等、任意の形態で調製されうる。 In addition to glycylglycine and retinol, optional compounding ingredients used in cosmetics, pharmaceuticals, etc. can be appropriately blended in such external skin preparations as necessary. In addition, external skin preparations include external solids, external powders, external liquids, liniments, sprays, external aerosols, pump sprays, ointments, creams, gels, patches, tapes, poultices, etc. It can be prepared in any form.
　本開示にかかるたるみ毛穴改善剤または皮膚外用剤は、その効果を損なわない範囲で、化粧品や医薬品等に用いられる任意配合成分を、必要に応じて適宜配合することができる。前記任意配合成分としては、例えば、油分、界面活性剤、粉末、色材、水、アルコール類、増粘剤、キレート剤、シリコーン類、酸化防止剤、紫外線吸収剤、保湿剤、香料、各種薬効成分、防腐剤、ｐＨ調整剤、中和剤などが挙げられる。他の成分として、例えば他の抗炎症成分、美白成分などが含まれていてもよい。 The sagging pore improving agent or skin preparation for external use according to the present disclosure can be appropriately blended with arbitrary compounding ingredients used in cosmetics, pharmaceuticals, etc., as necessary, as long as the effects are not impaired. Examples of the optional ingredients include oils, surfactants, powders, colorants, water, alcohols, thickeners, chelating agents, silicones, antioxidants, UV absorbers, moisturizers, fragrances, and various medicinal effects. Ingredients, preservatives, pH adjusters, neutralizers, and the like. Other ingredients may include, for example, other anti-inflammatory ingredients, whitening ingredients, and the like.
　例えば、クリーム剤は、グリシルグリシンとレチノールに加えて、水、アルコール、保湿剤、増粘剤、被膜剤、活性剤、油分、安定化剤、経皮吸収抑制剤、色剤、キレート剤、緩衝剤、防腐剤、香料などを含むことができる。 For example, creams contain, in addition to glycylglycine and retinol, water, alcohol, humectants, thickeners, film-forming agents, activators, oils, stabilizers, percutaneous absorption inhibitors, coloring agents, chelating agents, Buffers, preservatives, flavoring agents and the like may be included.
（美容方法および非治療的方法）
　一つの態様において、本発明は、本開示に従うたるみ毛穴改善剤、本開示に従う皮膚外用剤を対象の皮膚に適用する工程を含む、美容方法または非治療的方法に関する。対象は、哺乳動物でありうるが、好適にはヒトである。 (Cosmetic and non-therapeutic methods)
In one aspect, the present invention relates to a cosmetic or non-therapeutic method comprising applying a sagging pore improving agent according to the present disclosure, a topical skin preparation according to the present disclosure to the skin of a subject. The subject can be a mammal, but is preferably human.
　本明細書に開示のたるみ毛穴改善剤、または皮膚外用剤は、たるみ毛穴を改善するため、毛穴の形状の縦横比を改善するため、毛穴の大きさを縮小させるため、シワを改善するため、肌の弾力を改善するため、または肌の保湿性を改善するための美容または非治療的方法において用いることができる。本開示にかかる美容または非治療的方法においては、上記皮膚外用剤を所望の効果を得たい部位、例えば顔、首、手、腕、脚等に適用する。適用は、手や塗布具等によってする塗布など、任意の様式で行うことができる。適用の回数、頻度、量等は、所望の効果等に応じて適宜設定される。なお、本開示にかかる美容または非治療的方法は、いわゆる医療行為を含まない。 The sagging pore improving agent or skin external preparation disclosed herein improves sagging pores, improves the aspect ratio of the pore shape, reduces the pore size, improves wrinkles, It can be used in cosmetic or non-therapeutic methods to improve skin elasticity or to improve skin moisturization. In the cosmetic or non-therapeutic method according to the present disclosure, the external preparation for skin is applied to the site where the desired effect is desired, such as the face, neck, hands, arms, legs, and the like. Application can be in any manner, including application by hand, applicator, and the like. The number, frequency, amount, etc., of application are appropriately set according to the desired effect and the like. Note that the cosmetic or non-therapeutic method according to the present disclosure does not include so-called medical practice.
（使用）
　さらに、本開示の一つの態様は、たるみ毛穴を改善するため、毛穴の形状の縦横比を改善するため、毛穴の大きさを縮小させるため、シワを改善するため、肌の弾力を改善するため、または肌の保湿性を改善するための、グリシルグリシンとレチノールの組み合わせの使用に関する。本明細書に開示のデータは、グリシルグリシンとレチノールの組み合わせを含む組成物を肌に適用することによって、たるみ毛穴が改善され、肌の弾力性、保湿性、シワの改善が導かれることを示している。よって、グリシルグリシンとレチノールの組み合わせを含む組成物を用いて、たるみ毛穴改善等に使用するための皮膚外用剤や他の組成物を調製することができる。すなわち、本開示の一つの態様は、たるみ毛穴を改善するため、毛穴の形状の縦横比を改善するため、毛穴の大きさを縮小させるため、シワを改善するため、肌の弾力を改善するため、または肌の保湿性を改善するための皮膚外用剤の製造におけるグリシルグリシンとレチノールの組み合わせの使用にも関する。 (use)
Further, one aspect of the present disclosure is to improve sagging pores, improve aspect ratio of pore shape, reduce pore size, improve wrinkles, improve skin elasticity. , or the use of a combination of glycylglycine and retinol to improve skin moisturization. The data disclosed herein demonstrate that application of a composition comprising a combination of glycylglycine and retinol to the skin improves sagging pores leading to improved skin elasticity, moisture retention and wrinkles. showing. Thus, compositions containing a combination of glycylglycine and retinol can be used to prepare topical skin preparations and other compositions for use in improving sagging pores and the like. That is, one aspect of the present disclosure is to improve sagging pores, to improve the aspect ratio of the shape of pores, to reduce the size of pores, to improve wrinkles, to improve skin elasticity. , or the use of a combination of glycylglycine and retinol in the preparation of a topical skin preparation for improving skin moisturization.
　本明細書において言及される全ての文献はその全体が引用により本明細書に取り込まれる。 All documents referred to in this specification are hereby incorporated by reference in their entirety.
　以下に説明する本開示の実施例は例示のみを目的とし、本開示の技術的範囲を限定するものではない。本開示の技術的範囲は特許請求の範囲の記載によってのみ限定される。本開示の趣旨を逸脱しないことを条件として、本開示の変更、例えば、本開示の構成要件の追加、削除および置換を行うことができる。 The embodiments of the present disclosure described below are for illustrative purposes only and do not limit the technical scope of the present disclosure. The technical scope of the present disclosure is limited only by the description of the claims. Modifications of the disclosure, such as additions, deletions and substitutions of elements of the disclosure, may be made without departing from the spirit of the disclosure.
実施例１：グリシルグリシン＋レチノール配合クリームによる連用効果試験の概要
（目的）
　これまで有効成分が存在しない「たるみ毛穴の改善」を目的として、グリシルグリシン＋レチノール配合クリームによる連用効果試験を行った。
（方法）
　１９名の被験者を対象に、たるみ毛穴への効果が期待されるグリシルグリシン＋レチノール配合クリームを１２週間塗布し、毛穴形状ならびに肌パラメータを評価した。使用したクリームには、１．６％グリシルグリシンと０．２×１０４ＩＵ／gレチノールが含まれていた。１回の使用量は０．２ｇ（左右の頬に０．１ｇずつ）とし、朝晩１回ずつの使用とした。
（結果）
　頬部レプリカや肌画像診断装置（VISIA）を用いた解析の結果、試験製剤の適用により、毛穴のたるみ度（縦横比）は有意に改善し、毛穴面積も一部有意に縮小した。また、角層水分量は上昇、弾力も上昇し肌状態も良好になった。 Example 1: Outline of continuous use effect test of cream containing glycylglycine + retinol (purpose)
For the purpose of "improving sagging pores", for which no active ingredients existed so far, we conducted a continuous use effect test of a cream containing glycylglycine and retinol.
(Method)
A glycylglycine + retinol combination cream expected to be effective for sagging pores was applied to 19 subjects for 12 weeks, and pore shape and skin parameters were evaluated. The cream used contained 1.6% glycylglycine and 0.2×10 4 IU/g retinol. The amount to be used at one time was 0.2 g (0.1 g for each of the left and right cheeks), and was used once in the morning and once at night.
(result)
As a result of analysis using cheek replicas and skin imaging diagnostic equipment (VISIA), the application of the test formulation significantly improved the degree of sagging of pores (aspect ratio) and significantly reduced the area of some pores. In addition, the moisture content of the stratum corneum increased, the elasticity increased, and the skin condition improved.
実施例２：試験プロトコール
（被験者）
　４０代以降のたるみ毛穴に悩んでいる男女１９名（女性１４名、男性５名、５１．１±５．７歳）（平均±ＳＤ）を対象に試験を行った。
（連用期間）
　１．６％グリシルグリシンと０．２×１０４ＩＵ／gレチノールを配合したクリーム製剤を両頬部に１２週間連用した（０、４、８、１２週間後に測定を実施）。
（測定項目）
　毛穴のたるみ度と大きさ（レプリカ）、角層水分量、粘弾性（弾力、柔らかさ）、外観画像等を測定項目とした。なお、レプリカを用いた毛穴の評価は、特許第４２８６７２４号に記載のように、皮膚表面状態を採取したレプリカを採取し、共焦点顕微鏡を用いて計測することによりレプリカの三次元形状計測データを求めることができる。レプリカの基材にはSILFLO（アミックグループ）を使用することができる。角層水分量と粘弾性（弾力、柔らかさ）はCorneometer（CM825）、Cutometer（MPA580）などの市販の機器により測定することができる（Cutometerはプローブ径が２ｍｍのものを用い、４００ｍｂａｒで吸引し、測定した）。外観画像の解析にはVISIA Evolutionなどの市販の機器を使用することができる。なお、測定値の有意差検定は、測定値が正規分布に従う場合は対応あるt検定を、従わない場合はウィルコクソン順位和符号付検定（Wilcoxon signed rank test）を用いて行い、有意水準は０．０５とした。 Example 2: Test Protocol (Subjects)
A test was conducted on 19 males and females (14 females, 5 males, 51.1±5.7 years old) (mean±SD) suffering from sagging pores in their 40s and above.
(Continuous use period)
A cream formulation containing 1.6% glycylglycine and 0.2×10 4 IU/g retinol was continuously applied to both cheeks for 12 weeks (measurements were taken after 0, 4, 8 and 12 weeks).
(Measurement item)
Measurement items included the degree and size of pore sagging (replica), stratum corneum water content, viscoelasticity (elasticity, softness), appearance image, and the like. In the evaluation of pores using a replica, as described in Japanese Patent No. 4286724, a replica of the skin surface condition is collected and measured using a confocal microscope to obtain three-dimensional shape measurement data of the replica. can ask. SILFLO (Amic Group) can be used for the base material of the replica. The moisture content and viscoelasticity (elasticity, softness) of the stratum corneum can be measured by commercially available instruments such as Corneometer (CM825) and Cutometer (MPA580). ,It was measured). Commercially available equipment such as VISIA Evolution can be used to analyze appearance images. The significance test of the measured values was performed using the paired t-test when the measured values followed the normal distribution, and using the Wilcoxon signed rank test when the measured values did not follow the normal distribution. 05.
実施例３：頬部レプリカの毛穴解析結果
　試験製剤適用開始から０、４、８、１２週間後に取得した毛穴レプリカの３Ｄ解析を行い、統計的に解析した結果、毛穴縦横比（平均値）に有意な改善（８週間後ではｐ＜０．００１）が見られることが判明した（図１）。また、毛穴面積（平均値）も、有意ではないものの（ｐ＝０．１１）、毛穴の面積に縮小の傾向が見られた（図２）。これらの結果は、たるみ毛穴の改善、毛穴の形状の縦横比の改善、および毛穴の大きさの縮小のために、グリシルグリシンとレチノールとを含む組成物を使用できることを実証している。 Example 3: Pore Analysis Results of Cheek Replica Test Pore replicas obtained 0, 4, 8, and 12 weeks after the start of application of the formulation were subjected to 3D analysis, and statistically analyzed. As a result, the pore aspect ratio (average value) A significant improvement (p<0.001 after 8 weeks) was found (Figure 1). In addition, although the pore area (average value) was not significant (p=0.11), there was a tendency for the pore area to shrink (Fig. 2). These results demonstrate that a composition comprising glycylglycine and retinol can be used to improve sagging pores, improve aspect ratio of pore shape, and reduce pore size.
実施例４：VISIA画像からの解析結果
　VISIAで取得した外観画像の解析の結果、以下の表１および図３に示すように、毛穴スコアとしわスコアに有意な減少または減少の傾向が見られた。これらの結果は、毛穴の大きさの縮小とシワの改善のために、グリシルグリシンとレチノールとを含む組成物を使用できることを実証している。 Example 4: Results of Analysis from VISIA Images As a result of analysis of appearance images obtained with VISIA, as shown in Table 1 and FIG. . These results demonstrate that a composition comprising glycylglycine and retinol can be used for pore size reduction and wrinkle improvement.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
実施例５：測定機器データの解析結果
　測定機器で取得した角層水分量および柔らかさ、弾力の解析の結果、以下の表２および図４～６に示すように、角層水分量および柔らかさ、弾力に有意な改善または改善の傾向が見られた（＊はｐ＜０．０５、＊＊はｐ＜０．０１、＊＊＊はｐ＜０．００１の有意水準を表す）。これらの結果は、肌の保湿性および弾力（ハリ）の改善のために、グリシルグリシンとレチノールとを含む組成物を使用できることを実証している。 Example 5: Results of Analysis of Measuring Instrument Data The results of analysis of stratum corneum moisture content, softness, and elasticity obtained with the measuring instrument are shown in Table 2 below and FIGS. , there was a significant improvement or trend towards improvement in resilience ( * represents p<0.05, ** p<0.01, *** represents p<0.001 significance level). These results demonstrate that a composition comprising glycylglycine and retinol can be used to improve skin hydration and firmness.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
実施例６：被験者へのアンケート結果
　図７に示されるように、被験者に対してアンケートを行った結果でも、毛穴の改善傾向の実感が認められた。図７の左の積み上げグラフは、「毛穴が目立たなくなった」というアンケート項目の回答が１２週間後では「やや思う」と「そう思う」の合計で８０％を超える結果となったことを示している。右側のグラフは回答を数値化して平均を分析した結果であり、このグラフからも、毛穴が目立たなくなったとの実感が有意に増していることが見て取れる。
 

  Example 6 Results of Questionnaire to Subjects As shown in FIG. 7, the results of a questionnaire to the subjects also showed that the pores tended to improve. The stacked graph on the left side of FIG. 7 shows that the total of the responses to the questionnaire item “Pores are less noticeable” exceeds 80% after 12 weeks, with the total of “I think so” and “I think so”. there is The graph on the right shows the results of quantifying the responses and analyzing the averages. From this graph as well, it can be seen that the feeling that pores have become less noticeable has increased significantly.

Claims (13)

  1. 　グリシルグリシンとレチノールを含む、たるみ毛穴改善剤。 Sagging pore improvement agent containing glycylglycine and retinol.
  2. 　グリシルグリシンを０．５％以上２．０％以下含む、請求項１記載のたるみ毛穴改善剤。 The sagging pore improving agent according to claim 1, containing 0.5% or more and 2.0% or less of glycylglycine.
  3. 　レチノールを０．３×１０２ＩＵ／g以上１．０×１０５ＩＵ／ｇ以下含む、請求項１または２記載のたるみ毛穴改善剤。 The sagging pore improving agent according to claim 1 or 2, comprising 0.3 x 102 IU/g or more and 1.0 x 105 IU/g or less of retinol.
  4. 　毛穴の形状の縦横比を改善する、請求項１～３のいずれか一項記載のたるみ毛穴改善剤。 The sagging pore improving agent according to any one of claims 1 to 3, which improves the aspect ratio of the pore shape.
  5. 　毛穴の大きさを縮小させる、請求項１～４のいずれか一項記載のたるみ毛穴改善剤。 The sagging pore improving agent according to any one of claims 1 to 4, which reduces the size of pores.
  6. 　シワを改善する、請求項１～５のいずれか一項記載のたるみ毛穴改善剤。 The sagging pore improving agent according to any one of claims 1 to 5, which improves wrinkles.
  7. 　肌の弾力を改善する、請求項１～６のいずれか一項記載のたるみ毛穴改善剤。 The sagging pore improving agent according to any one of claims 1 to 6, which improves skin elasticity.
  8. 　肌の保湿性を改善する、請求項１～７のいずれか一項記載のたるみ毛穴改善剤。 The sagging pore improving agent according to any one of claims 1 to 7, which improves the moisturizing properties of the skin.
  9. 　請求項１～８のいずれか一項記載のたるみ毛穴改善剤を含む皮膚外用剤。 A skin external preparation containing the sagging pore improving agent according to any one of claims 1 to 8.
  10. 　請求項１～８のいずれか一項記載のたるみ毛穴改善剤または請求項９記載の皮膚外用剤を対象の皮膚に適用する工程を含む、美容方法。 A cosmetic method comprising the step of applying the agent for improving sagging pores according to any one of claims 1 to 8 or the external preparation for skin according to claim 9 to the skin of a subject.
  11. 　グリシルグリシンとレチノールを含む、シワ改善剤。 A wrinkle-improving agent containing glycylglycine and retinol.
  12. 　グリシルグリシンとレチノールを含む、肌弾力改善剤。 A skin elasticity improving agent containing glycylglycine and retinol.
  13. 　グリシルグリシンとレチノールを含む、肌保湿性改善剤。
     
     

          A skin moisturizing agent containing glycylglycine and retinol.
PCT/JP2022/037698 2021-10-22 2022-10-07 Agent for improving sagging pores WO2023068090A1 (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007013662A1 (en) * 2005-07-26 2007-02-01 Shiseido Company, Ltd. Wrinkle-preventive/ameliorating agent

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007013662A1 (en) * 2005-07-26 2007-02-01 Shiseido Company, Ltd. Wrinkle-preventive/ameliorating agent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE GNPD MINTEL; "Wrinkle Correcting Concentrate", XP093057820, Database accession no. 1854352 *

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