JP2022086491A - Type iii collagen production promoter and antiaging cosmetic - Google Patents

Type iii collagen production promoter and antiaging cosmetic Download PDF

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JP2022086491A
JP2022086491A JP2020198530A JP2020198530A JP2022086491A JP 2022086491 A JP2022086491 A JP 2022086491A JP 2020198530 A JP2020198530 A JP 2020198530A JP 2020198530 A JP2020198530 A JP 2020198530A JP 2022086491 A JP2022086491 A JP 2022086491A
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type iii
iii collagen
collagen production
production promoter
aging
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JP7276887B2 (en
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將義 久間
Masayoshi Hisama
素勉 池田
Motoyasu IKEDA
紗苗 久間
Sanae HISAMA
公男 吉尾
Kimio Yoshio
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Toyo Beauty Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • A61K31/683Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55Phosphorus compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64Proteins; Peptides; Derivatives or degradation products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin
    • A61Q19/08Anti-ageing preparations

Abstract

To provide a type III collagen production promoter that cause no skin irritation and is safe and can effectively promote the production of type III collagen, a component of collagen fibers, and to provide an anti-aging cosmetic that contains the type III collagen production promoter and shows a significant effect of improving wrinkles and sagging, the phenomena of skin aging.SOLUTION: A type III collagen production promoter comprises a composition containing isostearyl ascorbyl phosphate, represented by the formula shown below, or a metal salt thereof and a hydrolyzed eggshell membrane component as water-soluble components.SELECTED DRAWING: None

Description

この発明は、所定のアスコルビン酸誘導体及び卵殻膜成分を用いたIII型コラーゲン産生促進剤及びこれを含有する抗老化化粧料に関する。 The present invention relates to a type III collagen production promoter using a predetermined ascorbic acid derivative and eggshell membrane component, and an anti-aging cosmetic containing the same.

皮膚は、常に外界に曝されており、加齢と共にシワ、タルミ、くすみ、色素沈着などの老化現象が生じる。なかでも、シワやタルミといった皮膚形態の変化は、真皮マトリックスの90%以上を占めるコラーゲンによる影響が大きいと考えられている。 The skin is constantly exposed to the outside world, and aging phenomena such as wrinkles, tarmi, dullness, and pigmentation occur with aging. In particular, changes in skin morphology such as wrinkles and tarmi are thought to be largely affected by collagen, which accounts for 90% or more of the dermis matrix.

真皮コラーゲンの量は、加齢と共に減少し、コラーゲンの減少で真皮構造の形成が不完全になるため、皮膚は衰える。また、いわゆる「光老化皮膚」のコラーゲン量も通常の皮膚に比べて、著しくコラーゲン量が減少し、シワ、タルミの大きな要因の一つとして考えられている。 The amount of dermal collagen decreases with age, and the decrease in collagen results in incomplete formation of the dermal structure, resulting in skin deterioration. In addition, the amount of collagen in so-called "photoaging skin" is also significantly reduced as compared with normal skin, and is considered to be one of the major causes of wrinkles and tarmi.

コラーゲンの中でも特に、III型コラーゲンは、柔軟性を付与する働きがあると言われており、乳児の真皮組織中で成人の者と比べIII型コラーゲンの存在量は極めて高く、加齢に伴って急速に減少をする傾向のあることが知られている。 Among collagens, type III collagen is said to have a function of imparting flexibility, and the abundance of type III collagen in the dermis tissue of infants is extremely higher than that of adults, and with aging. It is known that it tends to decrease rapidly.

また、加齢を原因とする場合も含めて、III型コラーゲンの合成不全が原因であるコラーゲン線維形成機構異常を原因とするエーラス・ダンロス症候群の臨床症状IV型では、皮膚にシワが目立つ症状が確認されることも知られている。 In addition, in the clinical symptom type IV of Ehlers-Danlos syndrome caused by the abnormal collagen fibrosis mechanism caused by the deficiency of collagen synthesis of type III, including the case caused by aging, wrinkles are conspicuous on the skin. It is also known to be confirmed.

ところで、皮膚の加齢による形態変化を予防する薬剤またはシワ防止化粧品の有効成分として、レチノ-ルやレチノイン酸誘導体が用いられており、これはコラーゲン産生を促進する作用が知られている。 By the way, retinolu and retinoic acid derivatives are used as active ingredients of agents for preventing morphological changes due to aging of the skin or cosmetics for preventing wrinkles, and they are known to have an action of promoting collagen production.

しかし、このような有効成分を含有する従来のシワ防止化粧品は、皮膚刺激性が強く、また有効成分が非常に不安定な物質であるという欠点がある。 However, conventional anti-wrinkle cosmetics containing such an active ingredient have the disadvantages that they are highly irritating to the skin and that the active ingredient is a very unstable substance.

また、上記有効成分以外にコラーゲン産生促進効果のある有効成分としてアスコルビン酸が知られているが、このものは、皮膚浸透性が充分でなく、また熱や酸化に対して非常に不安定であり、使用前や使用中に不活性化されたり分解されたりしやすいため、必ずしも十分な生理作用が得られない場合がある。 In addition to the above active ingredients, ascorbic acid is known as an active ingredient having a collagen production promoting effect, but this has insufficient skin permeability and is extremely unstable to heat and oxidation. Since it is easily inactivated or decomposed before or during use, sufficient physiological action may not always be obtained.

アスコルビン酸の皮膚に対する浸透性を高めるために、リン酸エステル部が分岐したアルキル基を有するL-アスコルビン酸-2-リン酸エステルまたはその塩からなるアスコルビン酸誘導体からなるコラーゲン産生促進剤が知られている(特許文献1)。 In order to enhance the permeability of ascorbic acid to the skin, a collagen production promoter comprising an ascorbic acid derivative composed of L-ascorbic acid-2-phosphate ester having an alkyl group having a branched phosphate ester portion or a salt thereof is known. (Patent Document 1).

また、アスコルビン酸の不安定性を改善するために、グルコシド化した誘導体(特許文献2)も知られている。 In addition, a glucosided derivative (Patent Document 2) is also known for improving the instability of ascorbic acid.

一方、コラーゲンの産生またはシワ改善用に有効な素材として卵殻膜が知られている。
卵殻膜は、鶏卵などの鳥類の卵殻の内側の膜であり、内外2層から構成され、外卵殻膜は卵殻内面に密着し、内卵殻膜は卵白を包んでおり、発生中の胚を抗菌性により感染から保護している。
On the other hand, eggshell membranes are known as an effective material for collagen production or wrinkle improvement.
The eggshell membrane is the inner membrane of the eggshell of birds such as chicken eggs, and is composed of two inner and outer layers. Protects against infection by sex.

卵殻膜は、コラーゲン、グルコサミン、デスモシンおよびヒアルロン酸を主成分とした強靭な線維性タンパク質などから構成される網目構造を有し、これらのタンパク質は酸、アルカリ、プロテアーゼに対して比較的安定で、水に不溶性である。 The eggshell membrane has a network structure composed of tough fibrous proteins mainly composed of collagen, glucosamine, desmosine and hyaluronic acid, and these proteins are relatively stable to acids, alkalis and proteases. Insoluble in water.

また、卵角膜とコラーゲンを含有するコラーゲン産生促進剤(特許文献3)や加水分解卵角膜成分を含有するIII型コラーゲン産生を促進することを特徴とするシワ改善用組成物(特許文献4)や美容液(特許文献5)が知られてる。 In addition, a collagen production promoter containing egg cornea and collagen (Patent Document 3), a wrinkle improving composition (Patent Document 4) characterized by promoting the production of type III collagen containing a hydrolyzed egg cornea component, and the like. A beauty essence (Patent Document 5) is known.

特開2008-94750号公報Japanese Unexamined Patent Publication No. 2008-94750 特開平03-139288号公報Japanese Unexamined Patent Publication No. 03-139288 特開2012-153614号公報Japanese Unexamined Patent Publication No. 2012-153614 特開2018-188405号公報Japanese Unexamined Patent Publication No. 2018-188405 特開2019-137634号公報Japanese Unexamined Patent Publication No. 2019-137634

しかし、上記した特許文献1、2に記載されるアスコルビン酸誘導体と、特許文献3-5に記載される卵殻膜は、それぞれ単独で用いられているに留まり、せいぜい汎用のビタミンCとの偶発的な併用があったに過ぎない。 However, the ascorbic acid derivative described in Patent Documents 1 and 2 and the eggshell membrane described in Patent Document 3-5 are used alone, and at best, accidentally with general-purpose vitamin C. There was only a combination.

そのため、加齢による皮膚組織の老化現象に対して十分な効果のあるIII型コラーゲン産生促進剤および抗老化化粧料については知られていない。 Therefore, there is no known type III collagen production promoter and anti-aging cosmetics that are sufficiently effective against the aging phenomenon of skin tissue due to aging.

そこで、この発明の課題は、皮膚に対する刺激性がなく安全であり、かつコラーゲン線維の構成成分であるIII型コラーゲン量の産生を効果的に促進することができる優れたIII型コラーゲン産生促進剤を創製し、このIII型コラーゲン産生促進剤が配合され、加齢による皮膚老化現象であるシワ・たるみに対する顕著な改善効果を奏する抗老化化粧料を創製することである。 Therefore, the subject of the present invention is an excellent type III collagen production promoter that is not irritating to the skin, is safe, and can effectively promote the production of the amount of type III collagen, which is a component of collagen fibers. The purpose is to create an anti-aging cosmetic that is formulated with this type III collagen production promoter and has a remarkable improving effect on wrinkles and sagging, which are skin aging phenomena due to aging.

本願の発明者らは、III型コラーゲン産生促進効果が知られている成分の相乗効果を検証し、その結果、イソステアリルアスコルビルリン酸エステルまたはその金属塩および加水分解卵殻膜成分を含有する混合組成物において、III型コラーゲン産生を促進する優れた相乗作用を発揮することを見出し、さらにその混合組成物をカプセル殻構成成分とし、油溶性成分を内包させたカプセル化製剤が前記混合組成物よりも優れた作用を発揮することも見出した。さらに、本発明の混合組成物もしくはカプセル化製剤を含有した抗老化化粧料において優れたシワ・たるみを始めとした加齢による老化現象に対する改善効果を見出し、本発明を完成するに至った。 The inventors of the present application have verified the synergistic effect of a component known to have a type III collagen production promoting effect, and as a result, a mixed composition containing isostearyl ascorvir phosphate or a metal salt thereof and a hydrolyzed eggshell membrane component. It was found that the product exerts an excellent synergistic effect of promoting the production of type III collagen, and the encapsulated preparation containing the mixed composition as a capsule shell constituent component and containing an oil-soluble component is more than the above-mentioned mixed composition. It was also found that it exerts an excellent effect. Furthermore, the present invention has been completed by finding an improvement effect on the aging phenomenon due to aging such as excellent wrinkles and sagging in the anti-aging cosmetic containing the mixed composition or the encapsulated preparation of the present invention.

すなわちこの発明は、上記課題を解決するために、下記の化1の式で表わされるイソステアリルアスコルビルリン酸エステルまたはその金属塩(イソステアリルアスコルビルリン酸金属塩)、および加水分解卵殻膜成分を水溶性成分として含有する組成物からなるIII型コラーゲン産生促進剤としたのである。 That is, in order to solve the above-mentioned problems, the present invention comprises water-soluble isostearyl ascorvir phosphate or a metal salt thereof (isostearyl ascorvir phosphate metal salt) represented by the following formula (1) and a hydrolyzed eggshell membrane component. It was a type III collagen production promoter consisting of a composition contained as a sex component.

Figure 2022086491000001
Figure 2022086491000001

上記の組成物からなるIII型コラーゲン産生促進剤は、水溶性成分として、化1の式で表わされるイソステアリルアスコルビルリン酸エステルまたはその金属塩(イソステアリルアスコルビルリン酸エステル金属塩)および加水分解卵殻膜成分を併用して配合することにより、それぞれの成分を単独で配合した場合に比べて合算した以上の相乗的な作用があり、加齢による皮膚老化現象であるシワ・たるみの格別顕著な改善効果を奏する。 The type III collagen production promoter comprising the above composition has, as a water-soluble component, an isostearyl ascorvir phosphate ester represented by the formula of Chemical formula 1 or a metal salt thereof (isostearyl ascorvir phosphate ester metal salt) and a hydrolyzed eggshell. By blending the membrane components together, there is a synergistic effect that is more than the total when each component is blended alone, and there is a remarkable improvement in wrinkles and sagging, which is a skin aging phenomenon due to aging. It works.

このような所期した相乗効果が奏されるように、上記組成物における(イソステアリルアスコルビルリン酸エステルまたはその金属塩)/加水分解卵殻膜成分の割合が、質量比で1/1~1/8であることが好ましい。 The ratio of (isostearyl ascorbyl phosphate ester or a metal salt thereof) / hydrolyzed eggshell membrane component in the above composition is 1/1 to 1/1 by mass ratio so that such an expected synergistic effect is exhibited. It is preferably 8.

また、上記III型コラーゲン産生促進剤は、ナノメーターサイズの微粒子カプセル化製剤の剤型を採用することによって、その効果がより優れることが判明しているため、上記組成物を微粒子カプセルの構成成分とし、前記微粒子カプセルに油溶性成分を内包させた微粒子カプセル化製剤からなるIII型コラーゲン産生促進剤であることが好ましい。 Further, since it has been found that the effect of the type III collagen production promoter is more excellent by adopting the dosage form of the nanometer-sized fine particle capsule formulation, the above composition is used as a constituent component of the fine particle capsule. A type III collagen production-promoting agent comprising a fine particle-encapsulated preparation in which an oil-soluble component is encapsulated in the fine particle capsule is preferable.

また、このようにして得られるIII型コラーゲン産生促進剤を有効成分として含有する抗老化化粧料とすることにより、抗老化性の実用性が高められ、シワ・たるみの改善効果が充分に得られる。 Further, by using the anti-aging cosmetic containing the type III collagen production promoter thus obtained as an active ingredient, the practicality of anti-aging property is enhanced, and the effect of improving wrinkles and sagging can be sufficiently obtained. ..

この発明のIII型コラーゲン産生促進剤は、前記した化1の式で表わされるイソステアリルアスコルビルリン酸エステルまたはその金属塩および加水分解卵殻膜成分を水溶性成分として含有する組成物からなるので、皮膚に対する刺激性がなく安全であり、かつコラーゲン線維の構成成分であるIII型コラーゲン量の産生を効果的に促進することができる優れたIII型コラーゲン産生促進剤となる。そして、このIII型コラーゲン産生促進剤が配合された抗老化化粧料は、加齢による皮膚老化現象であるシワ・たるみに対する顕著な改善効果を奏するという利点がある。 Since the type III collagen production promoter of the present invention comprises a composition containing isostearyl ascorbyl phosphate ester represented by the above formula 1 or a metal salt thereof and a hydrolyzed eggshell membrane component as a water-soluble component, the skin. It is an excellent type III collagen production promoter that is not irritating to collagen, is safe, and can effectively promote the production of the amount of type III collagen, which is a component of collagen fibers. The anti-aging cosmetic containing this type III collagen production promoter has an advantage that it exerts a remarkable improving effect on wrinkles and sagging, which is a skin aging phenomenon due to aging.

実施例1及び比較例1、2のIII型コラーゲン産生促進効果のコントロールに対する相対比率を示す図表Chart showing the relative ratio of Example 1 and Comparative Examples 1 and 2 to the control of the type III collagen production promoting effect. 実施例2-5のIII型コラーゲン産生促進効果のコントロールに対する相対比率を示す図表Chart showing the relative ratio of Example 2-5 to the control of type III collagen production promoting effect

この発明のIII型コラーゲン産生促進剤の実施形態は、前記した化1の式で示されるイソステアリルアスコルビルリン酸エステルまたはその金属塩および加水分解された卵殻膜成分を水溶性成分として混合された組成物からなる。 The embodiment of the type III collagen production promoter of the present invention has a composition in which an isostearyl ascorbyl phosphate ester represented by the above formula 1 or a metal salt thereof and a hydrolyzed eggshell membrane component are mixed as a water-soluble component. It consists of things.

また、この混合組成物をカプセル殻構成成分とし、油溶性成分を内包させた微粒子カプセル化製剤は、他の実施形態であり、さらに、これらのIII型コラーゲン産生促進剤を有効成分として含有する抗老化化粧料も他の実施形態として後述する。 Further, a fine particle encapsulation preparation containing this mixed composition as a capsule shell constituent component and containing an oil-soluble component is another embodiment, and an anti-anti-aging agent containing these type III collagen production promoters as an active ingredient. Aging cosmetics will also be described later as another embodiment.

この発明に用いるイソステアリルアスコルビルリン酸エステルまたはその金属塩(イソステアリルアスコルビルリン酸2金属塩)は、リン酸エステル部が分岐したアルキル基を有するL-アスコルビン酸―2-リン酸エステルであり、適度な脂溶性があって細胞内に取り込まれやすく、その際に生体内に広く分布するフォスファターゼによって速やかにL-アスコルビン酸およびリン脂質などに分解され、皮膚の線維芽細胞において優れたIII型コラーゲン産生促進効果がある。 The isostearyl ascorvir phosphate or a metal salt thereof (isostearyl ascorvir phosphate dimetal salt) used in the present invention is an L-ascorbic acid-2-phosphate ester having an alkyl group having a branched phosphoric acid ester moiety. It has moderate lipophilicity and is easily taken up into cells. At that time, it is rapidly decomposed into L-ascorbic acid and phospholipids by phosphatase, which is widely distributed in the body, and is excellent type III collagen in skin fibroblasts. Has a production promoting effect.

イソステアリルアスコルビルリン酸エステル金属塩の具体例としては、以下の化2の式で示されるイソステアリルアスコルビルリン酸2ナトリウム塩が挙げられ、その他のアルカリ金属塩としてはカリウム塩等であってもよい。 Specific examples of the isostearyl ascorbyl phosphate metal salt include isostearyl ascorvir phosphate disodium salt represented by the following formula (2), and other alkali metal salts may be potassium salts and the like. ..

Figure 2022086491000002
Figure 2022086491000002

この発明に用いる加水分解卵殻膜成分は、卵殻膜もしくは卵殻膜含有粉末を、酸、アルカリ、アルカリ性有機溶媒、ならびにタンパク質分解酵素を含有する溶液によりタンパク質をペプチド、オリゴペプチド、必要に応じてアミノ酸に加水分解する既知の加水分解方法によって調製することができるものであり、水相及び油相への可溶性のため皮膚への親和性は高く、皮膚細胞への接着性も良好であり、単独でもある程度のIII型コラーゲン産生促進効果を示すものである。 The hydrolyzed eggshell membrane component used in the present invention is a hydrolyzed eggshell membrane or eggshell membrane-containing powder, which is converted into a peptide, oligopeptide, and optionally an amino acid by a solution containing an acid, an alkali, an alkaline organic solvent, and a proteolytic enzyme. It can be prepared by a known hydrolysis method that hydrolyzes, and because it is soluble in the aqueous and oil phases, it has a high affinity for the skin, has good adhesion to skin cells, and can be used alone to some extent. It shows the effect of promoting the production of type III collagen.

この発明で使用される加水分解卵殻膜成分は、上記いずれの方法によって製造された加水分解卵殻膜成分であっても用いることができる。また加水分解卵殻膜からアルコールや水性溶媒等で抽出されたエキスは、使用性や安定性のため、凍結乾燥などの乾燥手段により得られる粉末形態として使用されることが多くあるが、この発明に用いるために、例えば水やブチレングリコールなどの溶媒などに溶解した液状物として使用することもできる。また、特許文献4、5に記載されているような市販の加水分解卵殻膜成分が周知である。 The hydrolyzed eggshell membrane component used in the present invention can be any hydrolyzed eggshell membrane component produced by any of the above methods. Further, the extract extracted from the hydrolyzed eggshell membrane with alcohol, an aqueous solvent or the like is often used as a powder form obtained by a drying means such as freeze-drying because of its usability and stability. For use, it can also be used as a liquid substance dissolved in a solvent such as water or butylene glycol. Further, commercially available hydrolyzed eggshell membrane components as described in Patent Documents 4 and 5 are well known.

この発明のIII型コラーゲン産生促進剤の組成例としては、イソステアリルアスコルビルリン酸エステルまたはその金属塩(イソステアリルアスコルビルリン酸2ナトリウム塩)1~10質量%と、加水分解卵殻膜成分1~10質量%とを、グリセリン水溶液等の水性溶媒と混合撹拌し、そこに必要に応じて1~30重量%の油性成分を加えてホモジナイザーによる分散・乳化することによって混合組成物を調製することができる。 Examples of the composition of the type III collagen production promoter of the present invention include 1 to 10% by mass of isostearyl ascorvir phosphate or a metal salt thereof (isostearyl ascorvir phosphate disodium salt) and hydrolyzed eggshell membrane components 1 to 10. A mixed composition can be prepared by mixing and stirring the mass% with an aqueous solvent such as an aqueous solution of glycerin, adding an oily component of 1 to 30% by weight as necessary, and dispersing and emulsifying with a homogenizer. ..

さらに、得られた混合組成物を薄膜旋回型高速ミキサーや高圧乳化機などの一般的な微粒子化装置を使用し、微粒子化することにより皮膚浸透性に優れたナノサイズの微粒子カプセル化製剤を製造することができる。 Furthermore, the obtained mixed composition is atomized using a general atomizing device such as a thin film swirling high-speed mixer or a high-pressure emulsifier to produce a nano-sized fine particle-encapsulated formulation having excellent skin permeability. can do.

また、この発明のIII型コラーゲン産生促進剤は、後述する実施例の評価試験で実証されるように、III型コラーゲン産生促進機能を有し、III型コラーゲン産生促進剤として有用である。 In addition, the type III collagen production promoter of the present invention has a type III collagen production promoting function and is useful as a type III collagen production promoting agent, as demonstrated in the evaluation test of Examples described later.

この発明に係るIII型コラーゲン産生促進剤は、化粧料に有効成分として含有されて利用される他、化粧料やその他の皮膚外用剤に配合して皮膚の線維芽細胞においてIII型コラーゲン産生促進作用を発揮させることができ、III型コラーゲン産生促進作用に起因した加齢による皮膚老化現象であるシワ・たるみの改善効果などの抗老化作用などの機能を持たせ、抗老化用の皮膚外用剤などに調製できる。 The type III collagen production promoter according to the present invention is contained and used as an active ingredient in cosmetics, and is also used in cosmetics and other external preparations for skin to promote type III collagen production in skin fibroblasts. It has functions such as anti-aging effects such as the effect of improving wrinkles and sagging, which is a skin aging phenomenon due to aging caused by the type III collagen production promoting effect. Can be prepared.

この発明に係るIII型コラーゲン産生促進剤を所要の割合に配合して抗老化化粧料とする場合、III型コラーゲン産生促進剤の1種又は2種以上を配合してもよく、その配合量は、抗老化化粧料全量中に0.05質量%以上、例えば0.05~80質量%、好ましくは0.5~50質量%にすることが有効であり、かつ配合の効率もよい。 When the type III collagen production promoter according to the present invention is blended in a required ratio to make an anti-aging cosmetic, one or more of the type III collagen production promoter may be blended, and the blending amount thereof is It is effective to make 0.05% by mass or more, for example, 0.05 to 80% by mass, preferably 0.5 to 50% by mass in the total amount of the anti-aging cosmetics, and the compounding efficiency is also good.

因みに、安全性が周知である構成成分は、過剰に配合しても安全性に問題はなく、化粧料として皮膚刺激性で実用性を失しない濃度で配合可能である。 Incidentally, the constituents whose safety is well known have no problem in safety even if they are excessively blended, and can be blended as a cosmetic in a concentration that is irritating to the skin and does not lose its practicality.

この発明の抗老化化粧料には、上記の必須成分の他、通常の化粧料、医薬部外品、医薬品等に用いられる各種成分、例えば油性成分、乳化剤、保湿剤、増粘剤、薬効成分、防腐剤、顔料、粉体、pH調整剤、紫外線吸収剤、抗酸化剤、香料等を適宜配合することができる。 In addition to the above essential ingredients, the anti-aging cosmetics of the present invention include various ingredients used in ordinary cosmetics, non-pharmaceutical products, pharmaceuticals, etc., such as oily ingredients, emulsifiers, moisturizers, thickeners, and medicinal ingredients. , Preservatives, pigments, powders, pH adjusters, ultraviolet absorbers, antioxidants, fragrances and the like can be appropriately blended.

上記した油性成分の具体例としては、流動パラフィン、ワセリン、マイクロクリスタリンワックス、スクワラン、ホホバ油、ミツロウ、カルナウバロウ、ラノリン、オリーブ油、ヤシ油、高級アルコール、脂肪酸、イソステアリルアルコールなどの高級アルコールと脂肪酸のエステル、シリコーン油等が挙げられる。 Specific examples of the above-mentioned oily components include higher alcohols such as liquid paraffin, vaseline, microcrystalline wax, squalane, jojoba oil, beeswax, carnauba wax, lanolin, olive oil, palm oil, higher alcohols, fatty acids, and isostearyl alcohols. Examples thereof include esters and silicone oils.

上記の乳化剤としては、例えばポリオキシエチレンアルキルエーテル、ポリオキシエチレン脂肪酸エステル、ポリオキシエチレンソルビタン脂肪酸エステル、ソルビタン脂肪酸エステル、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油等の非イオン界面活性剤、ステアロイル乳酸ナトリウム等のアニオン界面活性剤、大豆リン脂質等の両性界面活性剤、塩化アルキルトリメチルアンモニウム等のカチオン界面活性剤が挙げられる。 Examples of the above emulsifier include nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, and polyoxyethylene hydrogenated castor oil. Examples thereof include an activator, an anionic surfactant such as stearoyl sodium lactate, an amphoteric surfactant such as soybean phospholipid, and a cationic surfactant such as alkyltrimethylammonium chloride.

上記の保湿剤としては、例えばグリセリン、ソルビトール、キシリトール、マルチトール、プロピレングリコール、ポリエチレングリコール、1,3-ブチレングリコール、1,2-ペンタンジオールなどが挙げられる。 Examples of the moisturizer include glycerin, sorbitol, xylitol, maltitol, propylene glycol, polyethylene glycol, 1,3-butylene glycol, 1,2-pentanediol and the like.

上記の増粘剤としては、例えばカルボキシビニルポリマー、(アクリレーツ/アクリル酸アルキル)クロスポリマー、キサンタンガム、メチルセルロース、ポリビニルピロリドン、ゼラチン、ベントナイト等の粘土鉱物等が挙げられる。 Examples of the thickener include carboxyvinyl polymers, (acrylitz / alkyl acrylate) crosspolymers, xanthan gum, methylcellulose, polyvinylpyrrolidone, gelatin, bentonite and other clay minerals.

その他の薬効成分としては、例えば各種ビタミンおよびその誘導体、アラントイン、グリチルリチン酸およびその誘導体、各種動植物抽出物等の老化防止剤、保湿剤、育毛剤、発毛剤、経皮吸収促進剤、紫外線吸収剤、細胞賦活剤、抗炎症剤、美白剤、防腐防カビ剤が挙げられる。 Other medicinal ingredients include, for example, various vitamins and their derivatives, allantin, glycyrrhizic acid and its derivatives, antiseptic agents such as various animal and plant extracts, moisturizers, hair growth agents, hair growth agents, transdermal absorption promoters, and ultraviolet absorption. Examples thereof include agents, cell activators, anti-inflammatory agents, whitening agents, and antiseptic and antifungal agents.

この発明のIII型コラーゲン産生促進剤を含む抗老化化粧料は、前記した混合組成物もしくはカプセル化製剤をIIIコラーゲン産生促進性の有効成分として配合することの他には、特に製造の条件を限定されるものではなく、周知の化粧料製造法により調製できる。 The anti-aging cosmetic containing the type III collagen production-promoting agent of the present invention is particularly limited in terms of production, in addition to blending the above-mentioned mixed composition or encapsulated preparation as an active ingredient for promoting III collagen production. It can be prepared by a well-known cosmetic manufacturing method.

またこの発明のIII型コラーゲン産生促進剤の用途は、国内外の法律や社会的事情などにより限定されず、医薬部外品、外用医薬品等にも適用でき、化粧料の剤型は目的に応じて選択でき、例えばクリーム状、乳液状、液状、ゲル状、軟膏状、パック状、スティック状、パウダー状等の形態を採用することができる。 Further, the use of the type III collagen production promoter of the present invention is not limited by domestic and foreign laws and social circumstances, and can be applied to non-pharmaceutical products, external medicines, etc., and the dosage form of cosmetics depends on the purpose. For example, cream-like, milky-liquid, liquid, gel-like, ointment-like, pack-like, stick-like, powder-like and the like can be adopted.

[実施例1]
イソステアリルアスコルビルリン酸2ナトリウム塩(前記化2の式で示されるもの、以下同じ)0.25質量%、市販の加水分解卵殻膜成分(卵殻膜のタンパク質をアルカリで加水分解したもの)0.1質量%、グリセリン/水が20/1(質量比)の混合液99.65質量%を混合撹拌した組成物からなる実施例1のIII型コラーゲン産生促進剤を得た。
[Example 1]
Isostearyl ascorbyl phosphate disodium salt (expressed by the formula of Chemical formula 2 above, the same applies hereinafter) 0.25% by mass, commercially available hydrolyzed eggshell membrane component (hydrolyzed eggshell membrane protein with alkali) 0. A type III collagen production promoter of Example 1 was obtained, which consisted of a composition obtained by mixing and stirring 1% by mass and 99.65% by mass of a mixed solution containing 20/1 (mass ratio) of glycerin / water.

[比較例1、2]
イソステアリルアスコルビルリン酸2ナトリウム塩0.25質量%と、グリセリン/水が20/1(質量比)の混合液99.75質量%とを混合撹拌した組成物からなる比較例1を得た。
[Comparative Examples 1 and 2]
Comparative Example 1 was obtained by mixing and stirring 0.25% by mass of isostearyl ascorbyl phosphate disodium salt and 99.75% by mass of a mixed solution of 20/1 (mass ratio) of glycerin / water.

また、市販の加水分解卵殻膜成分(卵殻膜のタンパク質をアルカリで加水分解したもの)0.1質量%、グリセリン/水が20/1(質量比)の混合液99.9質量%を混合撹拌した組成物からなる比較例2を得た。 In addition, 0.1% by mass of a commercially available hydrolyzed eggshell membrane component (protein of eggshell membrane hydrolyzed with alkali) and 99.9% by mass of a mixed solution containing 20/1 (mass ratio) of glycerin / water are mixed and stirred. Comparative Example 2 consisting of the above composition was obtained.

上記のようにして得られた実施例1、比較例1-2について、III型コラーゲン産生能を調べるために、以下のように試験を行ない、その結果を図1に示した。 The following tests were conducted on Example 1 and Comparative Example 1-2 obtained as described above in order to examine the type III collagen-producing ability, and the results are shown in FIG.

<実施例1、比較例1-2の線維芽細胞によるIII型コラーゲン産生能相乗効果の評価試験>
線維芽細胞は、5%子牛血清(FBS)含有DMEMを用いて96穴マイクロプレート
により0.5%FBS含有DMEMと交換した。72時間、試料含有培地で培養したのち、24時間培養後、Nucleospin RNA Plus (Machery-Nagel GmbH & Co.KG)を用いて、総RNAを抽出した。
<Evaluation test of synergistic effect of type III collagen production ability by fibroblasts of Example 1 and Comparative Example 1-2>
Fibroblasts were replaced with 0.5% FBS-containing DMEM by 96-well microplates using 5% fetal bovine serum (FBS) -containing DMEM. After culturing in a sample-containing medium for 72 hours, after culturing for 24 hours, total RNA was extracted using Nucleospin RNA Plus (Machery-Nagel GmbH & Co. KG).

この総RNAに対してPrime Script RT RCR Kit (タカラバイオ社製)を用いて逆転写を行い、cDNAを合成した。得られたcDNAを鋳型として、トロポエラスチン、GAPDHの発現量を以下のプライマー及び酵素を用いて、リアルタイムPCR(7500リアルタイムPCRシステム、アプライドバイオシステムズ社製)にて測定した。 Reverse transcription was performed on this total RNA using the Prime Script RT RCR Kit (manufactured by Takara Bio Inc.), and cDNA was synthesized. Using the obtained cDNA as a template, the expression levels of tropoelastin and GAPDH were measured by real-time PCR (7500 real-time PCR system, manufactured by Applied Biosystems) using the following primers and enzymes.

プライマーは、Col3a1(フォーワードプライマー:TCCCCTGAGAATCTGTGTGAATC、リバースプライマー:TGAGTCGAATTGGGGQATGT)を用いた。PCRの反応にはSYBR Select Master Mix(アプライドバイオシステムズ社製)を使用し、遺伝子発現の解析は比較Ct法にて行なった。 As a primer, Col3a1 (forward primer: TCCCCTGAGAATCTGTGTGAATC, reverse primer: TGAGTCGAATTTGGGQATGT) was used. SYBR Select Master Mix (manufactured by Applied Biosystems) was used for the PCR reaction, and the gene expression was analyzed by the comparative Ct method.

<試験結果>
図1に示される結果からも明らかなように、イソステアリルアスコルビルリン酸2ナトリウム塩および加水分解卵殻膜成分の混合物が未添加(コントロール)の場合に比べて、実施例1、比較例1、2は、明らかに高いIII型コラーゲン産生促進効果を示した。
<Test results>
As is clear from the results shown in FIG. 1, Example 1, Comparative Examples 1 and 2 are compared with the case where the mixture of isostearyl ascorbyl phosphate disodium salt and the hydrolyzed eggshell membrane component is not added (control). Showed a clearly high type III collagen production promoting effect.

さらに、実施例1のIII型コラーゲン産生促進効果は、イソステアリルアスコルビルリン酸2ナトリウム塩のみを配合した比較例1、および加水分解卵殻膜成分のみを配合した比較例2の同促進効果の総和よりも高い効果を示した。 Further, the type III collagen production promoting effect of Example 1 is based on the sum of the promoting effects of Comparative Example 1 containing only isostearyl ascorbyl phosphate disodium salt and Comparative Example 2 containing only the hydrolyzed eggshell membrane component. Also showed a high effect.

以上のことから、イソステアリルアスコルビルリン酸2ナトリウム塩および加水分解卵殻膜成分を併せて配合した実施例1は、III型コラーゲン産生促進効果において相乗効果を有していることは明らかであった。 From the above, it was clear that Example 1 in which the disodium isostearyl ascorbyl phosphate and the hydrolyzed eggshell membrane component were combined had a synergistic effect in the effect of promoting the production of type III collagen.

[実施例2、3]
イソステアリルアスコルビルリン酸2ナトリウム塩1.0質量%と、市販の加水分解卵殻膜成分(卵殻膜のタンパク質をアルカリで加水分解したもの)4.0質量%と、グリセリン/水が20/1(質量比)の混合液70.0質量%とを混合し、そこに25.0質量%のイソステアリルアルコールを加えてホモジナイザーによる分散・乳化することによって混合組成物Aからなる実施例2のIII型コラーゲン産生促進剤を得た。
[Examples 2 and 3]
Isostearyl ascorbyl phosphate disodium salt 1.0% by mass, commercially available hydrolyzed eggshell membrane component (hydrolyzed eggshell membrane protein with alkali) 4.0% by mass, and glycerin / water 20/1 ( Mixing with 70.0% by mass of the mixed solution of (mass ratio), 25.0% by mass of isostearyl alcohol is added thereto, and the mixture is dispersed and emulsified by a homogenizer to form Type III of Example 2 consisting of the mixed composition A. A collagen production promoter was obtained.

また、実施例2を薄膜旋回型高速ミキサーにより、微粒子化することにより微粒子カプセル化製剤Aからなる実施例3のIII型コラーゲン産生促進剤を得た。 Further, by atomizing Example 2 into fine particles with a thin film swirl type high-speed mixer, a type III collagen production promoter of Example 3 composed of the fine particle encapsulated preparation A was obtained.

得られた実施例2、3について、レーザ回折/散乱式粒子径分布測定装置(HORIBA製:LA-950)を用いて粒子径を測定した結果、実施例2の平均粒子径は14.87μmであり、微粒子カプセル化製剤Aである実施例3の平均粒子径は、228nmであった。 As a result of measuring the particle size of the obtained Examples 2 and 3 using a laser diffraction / scattering type particle size distribution measuring device (manufactured by HORIBA: LA-950), the average particle size of Example 2 was 14.87 μm. The average particle size of Example 3 of the fine particle encapsulating preparation A was 228 nm.

[実施例4、5]
イソステアリルアスコルビルリン酸2ナトリウム塩1.0質量%と、市販の加水分解卵殻膜成分(卵殻膜のタンパク質をアルカリで加水分解したもの)8.0質量%と、グリセリン/水が10/1(質量比)の混合液70.0質量%とを混合し、そこに22.0質量%のイソステアリルアルコールを加えてホモジナイザーによる分散・乳化することによって混合組成物Bからなる実施例4のIII型コラーゲン産生促進剤を得た。
[Examples 4 and 5]
Isostearyl ascorbyl phosphate disodium salt 1.0% by mass, commercially available hydrolyzed eggshell membrane component (hydrolyzed eggshell membrane protein with alkali) 8.0% by mass, and glycerin / water 10/1 ( A mixed solution of (mass ratio) (70.0% by mass) is mixed with 70.0% by mass, 22.0% by mass of isostearyl alcohol is added thereto, and the mixture is dispersed and emulsified by a homogenizer to form a mixed composition B, type III of Example 4. A collagen production promoter was obtained.

また、実施例4を高圧乳化機により微粒子化して微粒子カプセル化製剤Bからなる実施例5のIII型コラーゲン産生促進剤を得た。 Further, Example 4 was atomized by a high-pressure emulsifier to obtain a type III collagen production promoter of Example 5 composed of the fine particle-encapsulated preparation B.

得られた実施例4、5について、レーザ回折/散乱式粒子径分布測定装置(HORIBA製:LA-950)を用いて粒子径を測定した結果、実施例4の平均粒子径は8.77μmであり、微粒子カプセル化製剤Bである実施例5の平均粒子径は、128nmであった。 As a result of measuring the particle size of the obtained Examples 4 and 5 using a laser diffraction / scattering type particle size distribution measuring device (manufactured by HORIBA: LA-950), the average particle size of Example 4 was 8.77 μm. The average particle size of Example 5, which is the fine particle encapsulating preparation B, was 128 nm.

上記のようにして得られた実施例2-5について、III型コラーゲン産生能を調べるために、以下のように試験を行ない、その結果を図2に示した。 Examples 2-5 obtained as described above were tested as follows in order to examine the type III collagen-producing ability, and the results are shown in FIG.

<III型コラーゲン産生促進剤(実施例2-5)の線維芽細胞によるIII型コラーゲン産生能評価>
実施例1、比較例1-2に対するIII型コラーゲン産生能相乗効果評価試験と同様に試験を行ない、実施例2-5についてIII型コラーゲン産生促進効果を測定した。
<Evaluation of type III collagen production ability by fibroblasts of type III collagen production promoter (Example 2-5)>
The same test as in the type III collagen production ability synergistic effect evaluation test with respect to Example 1 and Comparative Example 1-2 was carried out, and the type III collagen production promoting effect was measured for Example 2-5.

<試験結果>
図2に示される結果からも明らかなように、実施例2(混合組成物A)、実施例3(微粒子カプセル化製剤A)、実施例4(混合組成物B)、ならびに実施例5(微粒子カプセル化製剤B)の混合物が未添加(コントロール)の場合に比べて、実施例2-5は明らかに高いIII型コラーゲン産生促進効果を示した。
<Test results>
As is clear from the results shown in FIG. 2, Example 2 (mixture composition A), Example 3 (fine particle encapsulated formulation A), Example 4 (mixture composition B), and Example 5 (fine particles). Example 2-5 showed a clearly higher type III collagen production promoting effect as compared with the case where the mixture of the encapsulated preparation B) was not added (control).

さらに、III型コラーゲン産生促進効果は、実施例2(混合組成物A)よりも実施例3(微粒子カプセル化製剤A)の方が、混合組成物Bよりも微粒子カプセル化製剤Bの方が、高いことから、微粒子カプセル化することにより皮膚浸透性が向上し、IIIコラーゲン産生促進効果が向上することが明らかになった。 Further, the effect of promoting the production of type III collagen is higher in Example 3 (fine particle encapsulated preparation A) than in Example 2 (mixed composition A), and in the fine particle encapsulated preparation B than in the mixed composition B. From the high value, it was clarified that the encapsulation of fine particles improved the skin permeability and the effect of promoting the production of III collagen.

[実施例6-17、比較例3-5]
以下の表1に示す配合割合(合計100重量%)でIII型コラーゲン産生促進剤を含有する化粧料組成物(化粧水)(実施例6~17)及びIII型コラーゲン産生促進成分としてイソステアリルアスコルビルリン酸2ナトリウム塩のみを配合した比較例3、もしくは加水分解卵殻膜成分のみを配合した比較例4、またはそれらのいずれも配合しなかった比較例5を調製した。
[Example 6-17, Comparative Example 3-5]
Cosmetic compositions (toners) (Examples 6 to 17) containing a type III collagen production promoter in the blending ratios (total 100% by weight) shown in Table 1 below, and isostearyl ascorbyl as a type III collagen production promoting component. Comparative Example 3 in which only the sodium phosphate 2 was blended, Comparative Example 4 in which only the hydrolyzed eggshell membrane component was blended, or Comparative Example 5 in which none of them was blended was prepared.

これらの実施例6-17、比較例3-5に対し、以下の試験を行なって、ヒトによる抗老化効果を評価した。
<ヒトによる抗老化効果の評価試験>
加齢による皮膚老化の悩みを持つ被験者を一群20名とし、実施例6-17、比較例3-5の化粧料を毎日、朝と夜、3ヶ月間塗布使用させ、3ヶ月後に累積塗布効果を以下の判定基準により自己判定させ、さらに判定結果を以下の基準で評価し、その結果を表1中に併記した。
The following tests were performed on these Examples 6-17 and Comparative Example 3-5 to evaluate the anti-aging effect by humans.
<Evaluation test of anti-aging effect by humans>
A group of 20 subjects suffering from skin aging due to aging, and the cosmetics of Example 6-17 and Comparative Example 3-5 were applied daily for 3 months in the morning and at night, and the cumulative application effect was applied after 3 months. Was self-judged according to the following criteria, and the determination results were evaluated according to the following criteria, and the results are also shown in Table 1.

[評価]
◎:被験者のうち著効、有効の示す割合(有効率)が80%以上。
○:被験者のうち著効、有効の示す割合(有効率)が60%以上80%未満。
△:被験者のうち著効、有効の示す割合(有効率)が40%以上60%未満。
×:被験者のうち著効、有効の示す割合(有効率)が40%未満。
ただし、有効性の判定基準は以下の通りとした。
著効:シワ、タルミがほとんど目立たなくなった。
有効:シワ、タルミが少し目立たなくなった。
やや有効:シワ、タルミがやや目立たなくなった。
無効:変化なし。
[evaluation]
⊚: Among the subjects, the ratio (effective rate) showing significant effect and effectiveness is 80% or more.
◯: The percentage (effective rate) of the subjects that showed significant efficacy and efficacy was 60% or more and less than 80%.
Δ: The percentage of subjects showing significant efficacy and efficacy (effective rate) is 40% or more and less than 60%.
×: The percentage of subjects showing significant efficacy and efficacy (effective rate) is less than 40%.
However, the criteria for determining effectiveness are as follows.
Significant effect: Wrinkles and tarmi have become almost inconspicuous.
Effective: Wrinkles and tarmi have become a little less noticeable.
Slightly effective: Wrinkles and tarmi have become slightly less noticeable.
Invalid: No change.

Figure 2022086491000003
Figure 2022086491000003

表1に示された結果からも明らかなように、実施例6-17のIII型コラーゲン産生促進剤を有効成分とする化粧料(皮膚外用剤)は有用であり、皮膚の線維芽細胞にIII型コラーゲン産生促進作用を奏し、III型コラーゲン量の富化によるシワ、タルミの改善効果等によって抗老化作用の機能を持し、抗老化化粧料として有用であることが判る。 As is clear from the results shown in Table 1, the cosmetic (external skin preparation) containing the type III collagen production promoter of Example 6-17 as an active ingredient is useful, and is useful for skin fibroblasts III. It has an anti-aging effect due to the effect of promoting the production of type collagen and the effect of improving wrinkles and tarmi by enriching the amount of type III collagen, and it can be seen that it is useful as an anti-aging cosmetic.

以下に、所定のIII型コラーゲン産生促進剤を有効成分とする実施例として、化粧料の代表的な処方例を示す。各行右端の数値は配合割合(重量%)である。なお、得られた処方例による化粧料は、有効成分量のIII型コラーゲン産生促進剤を含有し、シワ、タルミの改善効果等を奏する抗老化化粧料である。 Below, a typical prescription example of a cosmetic is shown as an example containing a predetermined type III collagen production promoter as an active ingredient. The numerical value at the right end of each line is the blending ratio (% by weight). The cosmetic according to the obtained prescription example is an anti-aging cosmetic that contains an active ingredient amount of a type III collagen production promoter and has an effect of improving wrinkles and tarmi.

[処方例1](ゲル状クリーム)
混合組成物A 5.0
グリセリン 5.0
エタノール 5.0
水酸化ナトリウム 0.5
カルボキシビニルポリマー 0.8
香料 適量
防腐剤 適量
精製水 残余
[Prescription Example 1] (Gel cream)
Mixed Composition A 5.0
Glycerin 5.0
Ethanol 5.0
Sodium hydroxide 0.5
Carboxyvinyl polymer 0.8
Fragrance Appropriate amount Preservative Appropriate amount Purified water Residual

[処方例2](乳液)
微粒子カプセル化製剤A 10.0
1,3-ブチレングリコール 10.0
カルボキシビニルポリマー 0.3
スクワラン 5.0
セタノール 0.6
L-アルギニン 0.3
香料 適量
防腐剤 適量
精製水 残余
[Prescription example 2] (milky lotion)
Fine particle encapsulation formulation A 10.0
1,3-butylene glycol 10.0
Carboxyvinyl polymer 0.3
Squalene 5.0
Cetanol 0.6
L-Arginine 0.3
Fragrance Appropriate amount Preservative Appropriate amount Purified water Residual

[処方例3](クリーム)
微粒子カプセル化製剤B 20.0
1,3-ブチレングリコール 10.0
カルボキシビニルポリマー 0.4
スクワラン 5.0
セタノール 3.0
ミツロウ 3.0
L-アルギニン 0.3
香料 適量
防腐剤 適量
精製水 残余
[Prescription Example 3] (Cream)
Fine particle encapsulation product B 20.0
1,3-butylene glycol 10.0
Carboxyvinyl polymer 0.4
Squalene 5.0
Cetanol 3.0
Beeswax 3.0
L-Arginine 0.3
Fragrance Appropriate amount Preservative Appropriate amount Purified water Residual

参考例1]
イソステアリルアスコルビルリン酸2ナトリウム塩(前記化2の式で示されるもの、以下同じ)0.25質量%、市販の加水分解卵殻膜成分(卵殻膜のタンパク質をアルカリで加水分解したもの)0.1質量%、グリセリン/水が20/1(質量比)の混合液99.65質量%を混合撹拌した組成物からなる参考例1のIII型コラーゲン産生促進剤を得た。
[ Reference Example 1]
Isostearyl ascorbyl phosphate disodium salt (expressed by the formula of Chemical formula 2 above, the same applies hereinafter) 0.25% by mass, commercially available hydrolyzed eggshell membrane component (hydrolyzed eggshell membrane protein with alkali) 0. A type III collagen production promoter of Reference Example 1 was obtained, which consisted of a composition obtained by mixing and stirring 1% by mass and 99.65% by mass of a mixed solution containing 20/1 (mass ratio) of glycerin / water.

上記のようにして得られた参考例1、比較例1-2について、III型コラーゲン産生能
を調べるために、以下のように試験を行ない、その結果を図1に示した。
In order to investigate the type III collagen-producing ability of Reference Example 1 and Comparative Example 1-2 obtained as described above, the following tests were conducted, and the results are shown in FIG.

参考例1、比較例1-2の線維芽細胞によるIII型コラーゲン産生能相乗効果の評価試験>
線維芽細胞は、5%子牛血清(FBS)含有DMEMを用いて96穴マイクロプレート
により0.5%FBS含有DMEMと交換した。72時間、試料含有培地で培養したのち、24時間培養後、Nucleospin RNA Plus (Machery-Nagel GmbH & Co.KG)を用いて、総RNAを抽出した。
<Evaluation test of synergistic effect of type III collagen production ability by fibroblasts of Reference Example 1 and Comparative Example 1-2>
Fibroblasts were replaced with 0.5% FBS-containing DMEM by 96-well microplates using 5% fetal bovine serum (FBS) -containing DMEM. After culturing in a sample-containing medium for 72 hours, after culturing for 24 hours, total RNA was extracted using Nucleospin RNA Plus (Machery-Nagel GmbH & Co. KG).

<試験結果>
図1に示される結果からも明らかなように、イソステアリルアスコルビルリン酸2ナトリウム塩および加水分解卵殻膜成分の混合物が未添加(コントロール)の場合に比べて、参考例1、比較例1、2は、明らかに高いIII型コラーゲン産生促進効果を示した。
<Test results>
As is clear from the results shown in FIG. 1, Reference Example 1, Comparative Examples 1 and 2 are compared with the case where the mixture of isostearyl ascorbyl phosphate disodium salt and the hydrolyzed eggshell membrane component is not added (control). Showed a clearly high type III collagen production promoting effect.

さらに、参考例1のIII型コラーゲン産生促進効果は、イソステアリルアスコルビルリン酸2ナトリウム塩のみを配合した比較例1、および加水分解卵殻膜成分のみを配合した比較例2の同促進効果の総和よりも高い効果を示した。 Further, the type III collagen production promoting effect of Reference Example 1 is based on the sum of the promoting effects of Comparative Example 1 containing only isostearyl ascorbyl phosphate disodium salt and Comparative Example 2 containing only the hydrolyzed eggshell membrane component. Also showed a high effect.

<III型コラーゲン産生促進剤(実施例2-5)の線維芽細胞によるIII型コラーゲン産生能評価>
参考例1、比較例1-2に対するIII型コラーゲン産生能相乗効果評価試験と同様に試験を行ない、実施例2-5についてIII型コラーゲン産生促進効果を測定した。
<Evaluation of type III collagen production ability by fibroblasts of type III collagen production promoter (Example 2-5)>
The same test as in the type III collagen production ability synergistic effect evaluation test with respect to Reference Example 1 and Comparative Example 1-2 was carried out, and the type III collagen production promoting effect was measured for Example 2-5.

Claims (4)

下記の化1の式で表わされるイソステアリルアスコルビルリン酸エステルまたはその金属塩および加水分解卵殻膜成分を水溶性成分として含有する組成物からなるIII型コラーゲン産生促進剤。
Figure 2022086491000004
A type III collagen production promoter comprising a composition containing isostearyl ascorbyl phosphate ester represented by the following formula (1) or a metal salt thereof and a hydrolyzed eggshell membrane component as a water-soluble component.
Figure 2022086491000004
上記組成物における(イソステアリルアスコルビルリン酸エステルまたはその金属塩)/加水分解卵殻膜成分の割合が、質量比で1/1~1/8である請求項1に記載のIII型コラーゲン産生促進剤。 The type III collagen production promoter according to claim 1, wherein the ratio of (isostearyl ascorbyl phosphate ester or a metal salt thereof) / hydrolyzed eggshell membrane component in the above composition is 1/1 to 1/8 by mass ratio. .. 上記組成物を微粒子カプセルの構成成分とし、前記微粒子カプセルに油溶性成分を内包させた微粒子カプセル化製剤からなる請求項1または2に記載のIII型コラーゲン産生促進剤。 The type III collagen production-promoting agent according to claim 1 or 2, wherein the composition is a constituent component of a fine particle capsule, and the fine particle capsule contains an oil-soluble component. 請求項1~3のいずれかに記載のIII型コラーゲン産生促進剤を有効成分として含有する抗老化化粧料。 An anti-aging cosmetic containing the type III collagen production promoter according to any one of claims 1 to 3 as an active ingredient.
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KR100557196B1 (en) * 2004-09-21 2006-03-03 엔프라니 주식회사 Composition with high moisturing effects, method for nano-capsulating the same and cosmetic composition containing the nano-capsulated composition

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