JP2012077017A - Skin collagen production-promoting agent - Google Patents
Skin collagen production-promoting agent Download PDFInfo
- Publication number
- JP2012077017A JP2012077017A JP2010222098A JP2010222098A JP2012077017A JP 2012077017 A JP2012077017 A JP 2012077017A JP 2010222098 A JP2010222098 A JP 2010222098A JP 2010222098 A JP2010222098 A JP 2010222098A JP 2012077017 A JP2012077017 A JP 2012077017A
- Authority
- JP
- Japan
- Prior art keywords
- milk protein
- protein fraction
- skin collagen
- collagen production
- milk
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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Classifications
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- A—HUMAN NECESSITIES
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- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
- A23L2/66—Proteins
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/19—Dairy proteins
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/20—Milk; Whey; Colostrum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
- A61K38/018—Hydrolysed proteins; Derivatives thereof from animals from milk
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- 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
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- 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
- A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
- A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
- A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
- A61K8/986—Milk; Derivatives thereof, e.g. butter
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- 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
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- 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
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/83—Electrophoresis; Electrodes; Electrolytic phenomena
Abstract
Description
本発明は、皮膚の荒れ、シワ、弾性低下等を防止するのに有用な皮膚コラーゲン産生促進剤、皮膚コラーゲン産生促進用飲食品及び皮膚コラーゲン産生促進用化粧料に関する。さらに詳しくは、本発明は、乳タンパク質画分及び／または、その乳タンパク質画分の分解物を有効成分とする皮膚コラーゲン産生促進剤に関する。 The present invention relates to a skin collagen production promoter, a food and drink for promoting skin collagen production, and a cosmetic for promoting skin collagen production, which are useful for preventing rough skin, wrinkles, a decrease in elasticity, and the like. More specifically, the present invention relates to a skin collagen production promoter containing a milk protein fraction and / or a degradation product of the milk protein fraction as an active ingredient.
近年、皮膚のメカニズムに関する研究が進められ、皮膚の乾燥感や肌荒れの原因としてマクロ的には、加齢による新陳代謝の減衰によるもののほかに、太陽光（紫外線）、乾燥、酸化等の作用が複雑に関与していることが確認されてきた。これらの因子による作用によって、真皮の最も主要なマトリックス成分であるコラーゲン繊維が顕著に減少していることが明らかとなってきた。コラーゲン繊維によって保たれていた皮膚のハリや弾力性といった張力保持機構が紫外線等の作用によって破壊されると、皮膚はシワやたるみを増した状態になる。また、コラーゲンはその分子中に水分を保持することができ、それにより、皮膚をしっとりとした状態に保つことにも役立っているから、外的因子により、コラーゲンが破壊されると肌は、乾燥し、荒れた状態になる。以上のことから、真皮層の主要な成分の一つであるコラーゲンの生合成を促進させることにより、皮膚のシワやたるみを防止でき、しかも安全性の点でも問題のない皮膚コラーゲン産生促進剤が望まれていた。 In recent years, research on the mechanism of the skin has progressed, and macroscopically, the effects of sunlight (ultraviolet rays), drying, oxidation, etc. are complicated in addition to the deterioration of metabolism due to aging as a cause of skin dryness and rough skin. Has been confirmed to be involved. It has been clarified that collagen fibers, which are the main matrix components of the dermis, are significantly reduced by the action of these factors. When the tension retention mechanism such as skin elasticity and elasticity held by the collagen fibers is broken by the action of ultraviolet rays, the skin becomes wrinkled and sagging. Collagen can also retain moisture in its molecules, thereby helping to keep the skin moist, and when the collagen is destroyed by external factors, the skin becomes dry. And it becomes rough. From the above, it is possible to prevent skin wrinkles and sagging by promoting the biosynthesis of collagen, which is one of the main components of the dermis layer, and there is no problem in terms of safety. It was desired.
皮膚コラーゲン促進作用を有する物質としては、乳中に存在する塩基性タンパク質画分あるいはその塩基性タンパク質画分をタンパク質分解酵素で分解して得られる塩基性ペプチド画分（特許文献１）や、ラクトフェリンあるいはラクトフェリンをタンパク質分解酵素で分解して得られるラクトフェリン分解物（特許文献２）、ラクトパーオキシダーゼあるいはラクトパーオキシダーゼをタンパク質分解酵素で分解して得られるラクトパーオキシダーゼ分解物（特許文献３）、アンジオジェニンあるいはアンジオジェニンをタンパク質分解酵素で分解して得られるアンジオジェニン分解物（特許文献４）が既に知られている。 Examples of substances having a skin collagen promoting action include a basic protein fraction present in milk or a basic peptide fraction obtained by degrading the basic protein fraction with a proteolytic enzyme (Patent Document 1), lactoferrin Alternatively, a lactoferrin degradation product obtained by degrading lactoferrin with a proteolytic enzyme (Patent Document 2), lactoperoxidase or a lactoperoxidase degradation product obtained by degrading lactoperoxidase with a proteolytic enzyme (Patent Document 3), angio An angiogenin degradation product obtained by degrading genin or angiogenin with a proteolytic enzyme (Patent Document 4) is already known.
本発明は、皮膚の乾燥感や肌荒れ、シワやタルミを防止でき、しかも安全性の点でも問題のない食品素材としても使用可能な皮膚コラーゲンの生合成を促進する新たな皮膚コラーゲン産生促進剤を提供することを課題とする。また、本発明は、皮膚コラーゲン産生促進剤を配合した飲食品又は化粧料を提供することを課題とする。 The present invention provides a new skin collagen production promoter that promotes the biosynthesis of skin collagen that can be used as a food material that can prevent dryness, rough skin, wrinkles, and talmi, and that is safe in terms of safety. The issue is to provide. Moreover, this invention makes it a subject to provide the food / beverage products or cosmetics which mix | blended the skin collagen production promoter.
本発明者らは、これらの課題を解決するために、広く食品素材に含まれている皮膚コラーゲン産生促進作用を示す物質について鋭意、探索を進めていたところ、皮膚コラーゲン産生促進作用を示す乳タンパク質画分及び／または、その乳タンパク質画分の分解物を見出し、本発明を完成させるに至った。 In order to solve these problems, the inventors of the present invention have been diligently searching for substances that have a skin collagen production promoting action widely contained in food materials. A fraction and / or a degradation product of the milk protein fraction was found and the present invention was completed.
すなわち本発明は、以下の態様を含むものである。
（１）次の（ａ）から（ｃ）の特性を有する乳タンパク質画分を有効成分とする皮膚コラーゲン産生促進剤。
（ａ）乳由来であること。
（ｂ）ソディウムドデシルサルフェート−ポリアクリルアミドゲル（SDS-PAGE）電気泳動で、分子量７５，０００から８０，０００ダルトンの範囲のタンパク質を含有する画分であること。
（ｃ）構成アミノ酸組成中に塩基性アミノ酸を１３から１５重量％含有し、かつ、塩基性アミノ酸／酸性アミノ酸比が０．５から０．７の範囲であること。
（２）前記（ａ）から（ｃ）の特性を有する乳タンパク質画分の分解物を有効成分とする皮膚コラーゲン産生促進剤。
（３）（１）又は（２）に記載の乳タンパク質画分又は乳タンパク質画分の分解物を配合した皮膚コラーゲン産生促進用飲食品。
（４）（１）又は（２）に記載の乳タンパク質画分又は乳タンパク質画分の分解物を配合した皮膚コラーゲン産生促進用化粧料。
（５）次の（ａ）から（ｃ）の特性を有する乳タンパク質画分を、一日当たり１０μｇ以上経口摂取するか、又は０．００１〜２重量％になるよう塗布することによる皮膚コラーゲンの産生促進方法。
（ａ）乳由来であること。
（ｂ）ソディウムドデシルサルフェート−ポリアクリルアミドゲル（SDS-PAGE）電気泳動で、分子量７５，０００から８０，０００ダルトンの範囲のタンパク質を含有する画分であること。
（ｃ）構成アミノ酸組成中に塩基性アミノ酸を１３から１５重量％含有し、かつ、塩基性アミノ酸／酸性アミノ酸比が０．５から０．７の範囲であること。
（６）前記（ａ）から（ｃ）の特性を有する乳タンパク質画分の分解物を、一日当たり１０μｇ以上経口摂取するか、又は０．００１〜２重量％になるよう塗布することによる皮膚コラーゲンの産生促進方法。
That is, the present invention includes the following aspects.
(1) A skin collagen production promoter comprising a milk protein fraction having the following characteristics (a) to (c) as an active ingredient.
(A) It is derived from milk.
(B) A fraction containing a protein having a molecular weight in the range of 75,000 to 80,000 daltons by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE).
(C) The basic amino acid is contained in the constituent amino acid composition in an amount of 13 to 15% by weight, and the basic amino acid / acidic amino acid ratio is in the range of 0.5 to 0.7.
(2) A skin collagen production promoter comprising a degradation product of a milk protein fraction having the characteristics (a) to (c) as an active ingredient.
(3) A food / drink product for promoting skin collagen production, comprising the milk protein fraction according to (1) or (2) or a degradation product of the milk protein fraction.
(4) A skin collagen production promoting cosmetic comprising the milk protein fraction according to (1) or (2) or a degradation product of the milk protein fraction.
(5) Production of skin collagen by orally ingesting a milk protein fraction having the following characteristics (a) to (c) by 10 μg or more per day, or by applying to 0.001 to 2% by weight Promotion method.
(A) It is derived from milk.
(B) A fraction containing a protein having a molecular weight in the range of 75,000 to 80,000 daltons by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE).
(C) The basic amino acid is contained in the constituent amino acid composition in an amount of 13 to 15% by weight, and the basic amino acid / acidic amino acid ratio is in the range of 0.5 to 0.7.
(6) Skin collagen obtained by orally ingesting the degradation product of the milk protein fraction having the characteristics (a) to (c) above by 10 μg or more per day or by applying to 0.001 to 2% by weight. Production promotion method.
本発明の皮膚コラーゲン産生促進剤は、経口投与あるいは塗布により皮膚におけるコラーゲンの生合成を促進することから、皮膚の乾燥感や肌荒れ、シワや弾性低下等の防止に有用である。 Since the skin collagen production promoter of the present invention promotes collagen biosynthesis in the skin by oral administration or application, it is useful for preventing dryness of the skin, rough skin, wrinkles, reduced elasticity, and the like.
本発明の皮膚コラーゲン産生促進剤は、（ａ）乳由来であること、（ｂ）ソディウムドデシルサルフェート−ポリアクリルアミドゲル（SDS-PAGE）電気泳動で、分子量７５，０００から８０，０００ダルトンの範囲のタンパク質を含有する画分であること、（ｃ）構成アミノ酸組成中に塩基性アミノ酸を１３から１５重量％含有し、かつ、塩基性アミノ酸／酸性アミノ酸比が０．５から０．７の範囲であること、の３つの条件を全て満たす乳タンパク質画分か、あるいは当該乳タンパク質画分の分解物を有効成分とする。このような乳タンパク質画分は、例えば、脱脂乳や乳清等の乳原料を陽イオン交換樹脂と接触させて、０.２Ｍの食塩溶液で洗浄後、この樹脂に吸着した乳タンパク質を０．３５Ｍの食塩溶出液で溶出して得ることができる。なお、塩類としては、食塩の他カリウム塩、アンモニア塩、リン酸塩、酢酸塩、炭酸塩等を使用することができ、洗浄液のイオン強度を０．１５〜０.２５、溶出溶液のイオン強度を０.３〜０.４に適宜調整して、本発明の乳タンパク質画分を得ることができる。また、この溶出画分を回収し、逆浸透(ＲＯ)膜や電気透析(ＥＤ)法等により脱塩及び濃縮し、必要に応じて乾燥することにより得ることができる。逆浸透(ＲＯ)膜としては、Desal-3(Desalination社製)、HR-95(Dow Danmark社製)、NTR-729HF（日東電工社製）等を例示することができる。また、電気透析(ＥＤ)装置は、ユアサアイオニクス社や日本錬水社製の電気透析装置を例示できる。 The skin collagen production promoter of the present invention is (a) derived from milk, and (b) sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE) electrophoresis. A fraction containing protein, (c) 13 to 15% by weight of basic amino acids in the constituent amino acid composition, and a basic amino acid / acidic amino acid ratio in the range of 0.5 to 0.7 The active ingredient is a milk protein fraction that satisfies all three conditions, or a degradation product of the milk protein fraction. Such a milk protein fraction is prepared by, for example, bringing milk material such as skim milk or whey into contact with a cation exchange resin, washing it with a 0.2 M salt solution, and then adding 0. It can be obtained by elution with a 35M salt eluate. As salts, potassium salt, ammonia salt, phosphate, acetate, carbonate, etc. can be used in addition to sodium chloride, the ionic strength of the washing solution is 0.15 to 0.25, and the ionic strength of the elution solution Can be appropriately adjusted to 0.3 to 0.4 to obtain the milk protein fraction of the present invention. Further, this elution fraction can be collected, desalted and concentrated by reverse osmosis (RO) membrane, electrodialysis (ED) method or the like, and dried if necessary. Examples of the reverse osmosis (RO) membrane include Desal-3 (manufactured by Desalination), HR-95 (manufactured by Dow Danmark), NTR-729HF (manufactured by Nitto Denko), and the like. Examples of the electrodialysis (ED) device include electrodialysis devices manufactured by Yuasa Ionics and Nippon Ruisui.
また、乳由来のタンパク質画分を得る方法としては、乳又は乳由来の原料を陽イオン交換体に接触させた後、この陽イオン交換体に吸着した塩基性タンパク質画分を、pH５を超え、イオン強度 0.5を超える溶出液で溶出して得る方法（特開平5-202098号公報）、アルギン酸ゲルを用いて得る方法（特開昭 61-246198号公報）、無機の多孔性粒子を用いて乳清から得る方法（特開平 1-86839号公報）、硫酸化エステル化合物を用いて乳から得る方法（特開昭63-255300号公報）等が知られており、本発明の皮膚コラーゲン産生促進剤は、このような方法で得られる乳タンパク質画分を用いることができる。また、このようにして回収された乳タンパク質画分は、凍結乾燥等により粉末化して使用することも可能である。 Moreover, as a method for obtaining a protein fraction derived from milk, after bringing milk or a milk-derived raw material into contact with a cation exchanger, the basic protein fraction adsorbed on the cation exchanger exceeds pH 5, A method of elution with an eluent with an ionic strength exceeding 0.5 (Japanese Patent Laid-Open No. 5-202098), a method of using an alginate gel (Japanese Patent Laid-Open No. 61-246198), and milk using inorganic porous particles A method for obtaining from milk (Japanese Patent Laid-Open No. 1-86839), a method for obtaining from milk using a sulfated ester compound (Japanese Patent Laid-Open No. 63-255300), etc. are known. Can use the milk protein fraction obtained by such a method. In addition, the milk protein fraction collected in this way can be used after being pulverized by freeze-drying or the like.
本発明で用いる皮膚コラーゲン産生促進作用を有する乳タンパク質画分は、その構成アミノ酸組成中に塩基性アミノ酸を１３〜１５重量％含有し、かつ塩基性アミノ酸／酸性アミノ酸比が０．５〜０．７の範囲である。この範囲を外れると本願発明の効果を発揮することができない。また、本発明品は、分子量７５，０００〜８０，０００ダルトン、等電点が７.５〜８.５を示すタンパク質が主成分のタンパク質の混合物である。 The milk protein fraction having a skin collagen production promoting action used in the present invention contains 13 to 15% by weight of basic amino acids in its constituent amino acid composition, and the basic amino acid / acidic amino acid ratio is 0.5 to 0.00. The range is 7. Outside this range, the effects of the present invention cannot be exhibited. The product of the present invention is a protein-based protein mixture having a molecular weight of 75,000 to 80,000 daltons and an isoelectric point of 7.5 to 8.5.
乳タンパク質画分の分解物は、乳タンパク質画分と同様のアミノ酸組成を有しており、例えば、上記の方法で得られた乳タンパク質画分にペプシン、トリプシン、キモトリプシン等のタンパク質分解酵素を作用させ、さらに必要に応じ、パンクレアチン等のタンパク質分解酵素を作用させることにより、平均分子量４，０００以下の分解物として得ることができる。なお、乳タンパク質画分の分解物は、凍結乾燥等により粉末化して使用することも可能である。 The degradation product of the milk protein fraction has the same amino acid composition as that of the milk protein fraction. For example, a protease such as pepsin, trypsin or chymotrypsin acts on the milk protein fraction obtained by the above method. Furthermore, if necessary, a degradation product having an average molecular weight of 4,000 or less can be obtained by acting a proteolytic enzyme such as pancreatin. The degradation product of the milk protein fraction can also be used after being pulverized by freeze drying or the like.
本発明の皮膚コラーゲン産生促進剤の有効成分である乳タンパク質画分の給原となる乳又は乳由来原料としては、牛乳、人乳、山羊乳、羊乳等の乳を用いることができ、これらの乳をそのまま、あるいは、これらの乳の還元乳、脱脂乳、ホエー等を用いることができる。 As milk or a milk-derived raw material that serves as a source of the milk protein fraction that is the active ingredient of the skin collagen production promoter of the present invention, milk such as cow's milk, human milk, goat milk, and sheep milk can be used. These milks can be used as they are, or reduced milk, skim milk, whey and the like of these milks can be used.
本発明の皮膚コラーゲン産生促進剤は、経口投与あるいは塗布することにより、皮膚コラーゲン産生促進効果を発揮する。本発明の皮膚コラーゲン産生促進剤を経口投与するに際しては、有効成分である乳タンパク質画分又は乳タンパク質画分の分解物をそのままの状態で用いることもできるが、常法に従い、粉末剤、顆粒剤、錠剤、カプセル剤、ドリンク剤等に製剤化して用いることもできる。本発明において、粉末剤、顆粒剤、錠剤、カプセル剤等の経口剤は、例えば、澱粉、乳糖、白糖、マンニット、カルボキシメチルセルロース、コーンスターチ、無機塩類等の賦形剤を用いて常法によって製剤化される。この種の製剤には、前記賦形剤の他に、結合剤、崩壊剤、界面活性剤、滑沢剤、流動性促進剤、着色料、香料等を適宜使用することが出来る。より具体的には、結合剤としては、例えば、澱粉、デキストリン、アラビアガム末、ゼラチン、ヒドロキシプロピルスターチ、カルボキシメチルセルロースナトリウム、メチルセルロース、結晶性セルロース、エチルセルロース、ポリビニルピロリドンが挙げられる。また、崩壊剤としては、例えば、澱粉、ヒドロキシプロピルスターチ、カルボキシメチルセルロース、カルボキシメチルセルロースナトリウム、架橋カルボキシメチルセルロースナトリウム、結晶性セルロース等が挙げられる。界面活性剤としては、大豆レシチン、蔗糖脂肪酸エステル等が、滑沢剤としては、タルク、ロウ、蔗糖脂肪酸エステル、水素添加植物油等が、流動性促進剤としては無水ケイ酸、乾燥水酸化アルミニウム、ケイ酸マグネシウム等が挙げられる。 The skin collagen production promoter of the present invention exhibits an effect of promoting skin collagen production by oral administration or application. When orally administering the skin collagen production promoter of the present invention, the active ingredient milk protein fraction or the degradation product of the milk protein fraction can be used as it is. It can also be formulated into a medicine, tablet, capsule, drink or the like. In the present invention, oral preparations such as powders, granules, tablets and capsules are formulated by conventional methods using excipients such as starch, lactose, sucrose, mannitol, carboxymethylcellulose, corn starch, and inorganic salts. It becomes. In this type of preparation, in addition to the above-mentioned excipients, binders, disintegrants, surfactants, lubricants, fluidity promoters, colorants, fragrances and the like can be appropriately used. More specifically, examples of the binder include starch, dextrin, gum arabic powder, gelatin, hydroxypropyl starch, sodium carboxymethylcellulose, methylcellulose, crystalline cellulose, ethylcellulose, and polyvinylpyrrolidone. Examples of the disintegrant include starch, hydroxypropyl starch, carboxymethylcellulose, sodium carboxymethylcellulose, crosslinked sodium carboxymethylcellulose, and crystalline cellulose. As surfactant, soybean lecithin, sucrose fatty acid ester, etc., as lubricant, talc, wax, sucrose fatty acid ester, hydrogenated vegetable oil, etc., as fluidity promoter, anhydrous silicic acid, dry aluminum hydroxide, Examples include magnesium silicate.
さらには、これらの乳タンパク質画分又は乳タンパク質画分の分解物をそのままあるいは製剤化した後、これを栄養剤や飲食品等に配合することも可能である。また、ビタミンＣ等の従来からコラーゲン産生に有効な作用を持つと考えられている成分とともに乳タンパク質画分又は乳タンパク質画分の分解物を配合すれば、一層の皮膚コラーゲン産生促進作用が期待できる。なお、乳タンパク質画分又は乳タンパク質画分の分解物は、比較的熱に対して安定であるので、通常行われるような条件で加熱殺菌することも可能である。 Furthermore, it is also possible to mix these milk protein fractions or degradation products of the milk protein fractions as they are or into preparations, and then add them to nutrients, foods and drinks, and the like. Moreover, if a milk protein fraction or a degradation product of a milk protein fraction is blended together with components that are conventionally considered to have an effective action for collagen production such as vitamin C, further skin collagen production promoting action can be expected. . In addition, since the milk protein fraction or the degradation product of the milk protein fraction is relatively stable to heat, it can be sterilized by heating under the conditions usually used.
本発明の皮膚コラーゲン産生促進剤を塗布するに際しては、その使用目的に応じて、通常用いられる公知の成分に配合することによって、液剤、固形剤、半固形剤等の各種剤形に調製することが可能で、好ましい組成物として軟膏、ゲル、クリーム、スプレー剤、貼付剤、ローション、粉末等が挙げられる。例えば、本発明の皮膚コラーゲン産生促進剤をワセリン等の炭化水素、ステアリルアルコール、ミリスチン酸イソプロピル等の高級脂肪酸低級アルキルエステル、ラノリン等の動物性油脂、グリセリン等の多価アルコール、グリセリン脂肪酸エステル、モノステアリン酸、ポリエチレングリコール等の界面活性剤、無機塩、ロウ、樹脂、水及び、要すればパラオキシ安息香酸メチル、パラオキシ安息香酸ブチル等の保存料に混合することによって、皮膚コラーゲン産生促進用化粧料や医薬品を製造することができる。 When applying the skin collagen production promoter of the present invention, it is prepared into various dosage forms such as a liquid agent, a solid agent, a semi-solid agent, etc., by blending with commonly used known components according to the purpose of use. Preferred compositions include ointments, gels, creams, sprays, patches, lotions, powders and the like. For example, the skin collagen production promoter of the present invention is a hydrocarbon such as petrolatum, a higher fatty acid lower alkyl ester such as stearyl alcohol, isopropyl myristate, an animal fat such as lanolin, a polyhydric alcohol such as glycerin, a glycerin fatty acid ester, a monoester Cosmetics for promoting skin collagen production by mixing with surfactants such as stearic acid and polyethylene glycol, inorganic salts, waxes, resins, water and, if necessary, preservatives such as methyl paraoxybenzoate and butyl paraoxybenzoate And can produce medicines.
本発明の皮膚コラーゲン産生促進剤の経口投与による有効量は、その製剤形態、投与方法、使用目的、及びこれを適用される患者の年齢、体重、病状により適宜規定され一定でないが、ラットを用いた動物実験の結果によると、皮膚コラーゲン産生促進作用を示すためには、乳タンパク質画分又は乳タンパク質画分の分解物をラット体重１ｋｇ当たり１０μｇ以上摂取する必要があることが判った。したがって、外挿法によると、通常、成人一人当たり一日１０μｇ以上の乳タンパク質画分又は乳タンパク質画分の分解物を摂取すれば効果が期待できるので、この必要量を確保できるよう飲食品に配合するか、あるいは、医薬として投与すれば良い。なお、投与は必要に応じて一日数回に分けて行うことも可能である。 The effective amount of the skin collagen production promoter of the present invention by oral administration is appropriately defined by the formulation form, administration method, purpose of use, and age, weight, and medical condition of the patient to which it is applied, but is not constant. According to the results of animal experiments, it was found that it was necessary to ingest 10 μg or more of the milk protein fraction or the degradation product of the milk protein fraction per kg body weight of the rat in order to show the skin collagen production promoting action. Therefore, according to the extrapolation method, the effect can be expected by ingesting a milk protein fraction or a degradation product of milk protein fraction of 10 μg or more per adult per day. What is necessary is just to mix | blend or administer as a pharmaceutical. The administration can be divided into several times a day as necessary.
本発明の皮膚コラーゲン産生促進剤の塗布による有効量は、剤形により異なるが、適用する組成物全量を基準として、好ましくは、０．００１〜２重量％となるように、乳タンパク質画分又は乳タンパク質画分の分解物を配合すれば良い。ただし、入浴剤のように使用時に希釈されるものは、さらに配合量を増やすことができる。 The effective amount by application of the skin collagen production promoter of the present invention varies depending on the dosage form, but is preferably from 0.001 to 2% by weight based on the total amount of the composition to be applied. What is necessary is just to mix | blend the decomposition product of a milk protein fraction. However, what is diluted at the time of use like a bath agent can increase a compounding quantity further.
以下に、参考例、実施例及び試験例を示して本発明を詳細に説明するが、これらは単に本発明の実施態様を例示するものであり、本発明はこれらによって何ら限定されるものではない。 Hereinafter, the present invention will be described in detail with reference to reference examples, examples and test examples. However, these are merely examples of the present invention, and the present invention is not limited thereto. .
［参考例１］
下記の方法（特開2003−144095参照）により、皮膚コラーゲン産生促進作用が認められるの乳タンパク質画分を調製した。陽イオン交換樹脂のスルホン化キトパール(富士紡績製) ０．５リットルを充填した直径１０ｃｍのカラムを脱イオン水で充分洗浄した。このカラムに未殺菌脱脂乳 ５０リットルを流速１００ｍｌ／ｍｉｎで通液した後、このカラムを脱イオン水で充分洗浄し、０．９５Ｍ塩化ナトリウムを含む０．０５Ｍリン酸緩衝液(ｐＨ７．０)２．５リットルを通液して樹脂に吸着したタンパク質を溶出した。そして、この溶出液を逆浸透（ＲＯ）膜処理により、脱塩し、濃縮した後、凍結乾燥して粉末状の乳タンパク質画分を得た。この操作を２回繰り返して１０４ｇのタンパク質画分を得た。このタンパク質画分の等電点は７．０〜８．５であって、このタンパク質画分に含まれる塩基性アミノ酸は１７．８％であった。
[Reference Example 1]
By the following method (see Japanese Patent Application Laid-Open No. 2003-144095), a milk protein fraction that is recognized to promote skin collagen production was prepared. A 10 cm diameter column packed with 0.5 liter of a cation exchange resin sulfonated chitopearl (Fujibo) was thoroughly washed with deionized water. After 50 liters of non-sterilized skim milk was passed through the column at a flow rate of 100 ml / min, the column was thoroughly washed with deionized water, and 0.05 M phosphate buffer (pH 7.0) containing 0.95 M sodium chloride. The protein adsorbed on the resin was eluted by passing 2.5 liters. The eluate was desalted and concentrated by reverse osmosis (RO) membrane treatment, and then freeze-dried to obtain a powdered milk protein fraction. This operation was repeated twice to obtain 104 g of protein fraction. The isoelectric point of this protein fraction was 7.0 to 8.5, and the basic amino acid contained in this protein fraction was 17.8%.
陽イオン交換樹脂のスルホン化キトパール(富士紡績製) ０．５リットルを充填した直径１０ｃｍのカラムを脱イオン水で充分洗浄した。このカラムに未殺菌脱脂乳 ５０リットルを流速１００ｍｌ／ｍｉｎで通液した後、０.１５Ｍ塩化ナトリウムを含む０．０５Ｍリン酸緩衝液(ｐＨ７．０)で充分洗浄し、次いで、０.３Ｍ塩化ナトリウムを含む０.０５Ｍリン酸緩衝液（ｐＨ７.０）２.５リットルを通液して樹脂に吸着したタンパク質を溶出した。そして、この溶出液を逆浸透（ＲＯ）膜処理により、脱塩し、濃縮した後、凍結乾燥して粉末状の乳タンパク質画分を得た。この操作を３回繰り返して乳タンパク質画分５５.４ｇを得た。この画分は分子量７５，０００〜８０，０００ダルトンのタンパク質を含有し、等電点は７．５〜８．５であって、このタンパク質画分に含まれる構成アミノ酸のうち、塩基性アミノ酸は１３〜１５％であった。また、塩基性アミノ酸／酸性アミノ酸比は０．５〜０．７であった。得られた乳タンパク質画分はそのまま本願発明の皮膚コラーゲン産生促進剤として使用可能である。 A 10 cm diameter column packed with 0.5 liter of a cation exchange resin sulfonated chitopearl (Fujibo) was thoroughly washed with deionized water. After passing 50 liters of non-sterilized skim milk at a flow rate of 100 ml / min through this column, the column was thoroughly washed with 0.05 M phosphate buffer (pH 7.0) containing 0.15 M sodium chloride, and then 0.3 M chloride. The protein adsorbed on the resin was eluted by passing 2.5 liters of 0.05M phosphate buffer (pH 7.0) containing sodium. The eluate was desalted and concentrated by reverse osmosis (RO) membrane treatment, and then freeze-dried to obtain a powdered milk protein fraction. This operation was repeated three times to obtain 55.4 g of a milk protein fraction. This fraction contains a protein having a molecular weight of 75,000 to 80,000 daltons and has an isoelectric point of 7.5 to 8.5. Among the constituent amino acids contained in this protein fraction, basic amino acids are 13-15%. The basic amino acid / acidic amino acid ratio was 0.5 to 0.7. The obtained milk protein fraction can be used as it is as the skin collagen production promoter of the present invention.
陽イオン交換樹脂のスルホン化キトパール(富士紡績製) ０．５リットルを充填した直径１０ｃｍのカラムを脱イオン水で充分洗浄した。このカラムに未殺菌脱脂乳 ５０リットルを流速１００ｍｌ／ｍｉｎで通液した後、このカラムを０．２５Ｍ塩化ナトリウムを含む０．０５Ｍリン酸緩衝液(ｐＨ７．０)で充分洗浄し、０．４Ｍ塩化ナトリウムを含む０．０５Ｍリン酸緩衝液(ｐＨ７．０)２．５リットルを通液して樹脂に吸着したタンパク質を溶出した。そして、この溶出液を逆浸透（ＲＯ）膜処理により、脱塩し、濃縮した後、凍結乾燥して粉末状の乳タンパク質画分を得た。この操作を２回行い、乳タンパク質画分３７．３ｇを得た。この画分は分子量７５，０００〜８０，０００ダルトンのタンパク質を含有し、等電点は７．５〜８．５であって、この乳タンパク質画分に含まれる構成アミノ酸のうち，塩基性アミノ酸は１３〜１５％であった。また、塩基性アミノ酸／酸性アミノ酸比は０．５〜０．７であった。得られた乳タンパク質画分はそのまま本願発明の皮膚コラーゲン産生促進剤として使用可能である。 A 10 cm diameter column packed with 0.5 liter of a cation exchange resin sulfonated chitopearl (Fujibo) was thoroughly washed with deionized water. After 50 liters of non-sterilized skim milk was passed through the column at a flow rate of 100 ml / min, the column was sufficiently washed with 0.05 M phosphate buffer (pH 7.0) containing 0.25 M sodium chloride, and 0.4 M The protein adsorbed on the resin was eluted by passing 2.5 liters of 0.05 M phosphate buffer (pH 7.0) containing sodium chloride. The eluate was desalted and concentrated by reverse osmosis (RO) membrane treatment, and then freeze-dried to obtain a powdered milk protein fraction. This operation was performed twice to obtain 37.3 g of a milk protein fraction. This fraction contains a protein having a molecular weight of 75,000 to 80,000 daltons and has an isoelectric point of 7.5 to 8.5. Among the constituent amino acids contained in this milk protein fraction, basic amino acids Was 13-15%. The basic amino acid / acidic amino acid ratio was 0.5 to 0.7. The obtained milk protein fraction can be used as it is as the skin collagen production promoter of the present invention.
実施例１で得られた乳タンパク質画分５５．４ｇを蒸留水１０リットルに溶解した後、ペプシン（関東化学製）を２％濃度となるよう添加し、３７℃で１時間撹拌しながら加水分解した。次いで、水酸化ナトリウム溶液でｐＨ６．８に中和後、１％パンクレアチン（シグマ社製）を添加し、３７℃で２時間反応させた。反応後、８０℃で１０分間加熱処理して酵素を失活させた後、乳タンパク質画分の分解物５４．２ｇを得た。得られた乳タンパク質画分の分解物はそのまま本願発明の皮膚コラーゲン産生促進剤として使用可能である。 After 55.4 g of the milk protein fraction obtained in Example 1 was dissolved in 10 liters of distilled water, pepsin (manufactured by Kanto Chemical) was added to a concentration of 2%, and hydrolysis was performed while stirring at 37 ° C. for 1 hour. did. Subsequently, after neutralizing to pH 6.8 with a sodium hydroxide solution, 1% pancreatin (manufactured by Sigma) was added and reacted at 37 ° C. for 2 hours. After the reaction, the enzyme was inactivated by heat treatment at 80 ° C. for 10 minutes to obtain 54.2 g of a degradation product of the milk protein fraction. The degradation product of the obtained milk protein fraction can be used as it is as the skin collagen production promoter of the present invention.
実施例２で得られた乳タンパク質画分３７．３ｇを蒸留水８リットルに溶解した後、トリプシン（関東化学製）を２％濃度となるよう添加し、３７℃で１時間撹拌しながら加水分解した。次いで、水酸化ナトリウム溶液でｐＨ６．６に中和後、１％パンクレアチン（シグマ社製）を添加し、3７℃で２時間反応させた。反応後、８０℃で１０分間加熱処理して酵素を失活させた後、乳タンパク質画分の分解物３６．７ｇを得た。得られた乳タンパク質画分の分解物はそのまま本願発明の皮膚コラーゲン産生促進剤として使用可能である。 After 37.3 g of the milk protein fraction obtained in Example 2 was dissolved in 8 liters of distilled water, trypsin (manufactured by Kanto Chemical) was added to a concentration of 2%, and hydrolysis was carried out at 37 ° C. for 1 hour with stirring. did. Subsequently, after neutralizing to pH 6.6 with a sodium hydroxide solution, 1% pancreatin (manufactured by Sigma) was added and reacted at 37 ° C. for 2 hours. After the reaction, the enzyme was inactivated by heat treatment at 80 ° C. for 10 minutes to obtain 36.7 g of a degradation product of the milk protein fraction. The degradation product of the obtained milk protein fraction can be used as it is as the skin collagen production promoter of the present invention.
［試験例１］
参考例１で得られた乳タンパク質画分及び、実施例１で得られた乳タンパク質画分、実施例３で得られた乳タンパク質画分の分解物について、ラットを用いた動物実験によりコラーゲン産生促進作用を調べた。７週齢のＷｉｓｔａｒ系雄ラットを、生理食塩水投与群（Ａ群）、参考例１で得られた乳タンパク質画分をラット体重１ｋｇ当たり１０μｇ投与する群（Ｂ群）、参考例１で得られた乳タンパク質画分をラット体重１ｋｇ当たり１００μｇ投与する群（Ｃ群）、実施例１で得られた乳タンパク質画分をラット体重１ｋｇ当たり１０μｇ投与する群（Ｄ群）、実施例１で得られた乳タンパク質画分をラット体重１ｋｇ当たり１００μｇ投与する群（Ｅ群）、実施例３で得られた乳タンパク質画分の分解物をラット体重１ｋｇ当たり１０μｇ投与する群（Ｆ群）、実施例３で得られた乳タンパク質画分の分解物をラット体重１ｋｇ当たり１００μｇ投与する群（Ｇ群）の７試験群（ｎ＝６）に分け、それぞれを毎日１回ゾンデで投与して１０週間飼育した。皮膚のコラーゲン量については、ラットの真皮をＮｉｍｎｉらの方法（Ａｒｃｈ． Ｂｉｏｃｈｅｍ． Ｂｉｏｐｈｙｓ．， ２９２頁， １９６７年 参照）に準じて処理した後、可溶性画分に含まれるヒドロキシプロリン量を測定した。ヒドロキシプロリンはコラーゲンのみに含まれる特殊なアミノ酸で、コラーゲンを構成する全アミノ酸の約１０％を占めることからコラーゲン量の推定ができる（浅野隆司ら，Ｂｉｏ Ｉｎｄｕｓｔｏｒｙ，１２頁， ２００１年 参照）。その結果を表１に示す。
[Test Example 1]
Collagen production of the milk protein fraction obtained in Reference Example 1, the milk protein fraction obtained in Example 1, and the degradation product of the milk protein fraction obtained in Example 3 by animal experiments using rats The promoting effect was examined. Seven-week-old Wistar male rats were obtained in the physiological saline administration group (Group A), the group (Group B) in which the milk protein fraction obtained in Reference Example 1 was administered at 10 μg / kg of the rat body weight, and Reference Example 1. The group (group C) in which 100 μg of the obtained milk protein fraction was administered per kg of rat body weight, the group (group D) in which the milk protein fraction obtained in Example 1 was administered at 10 μg per kg of rat body weight were obtained in Example 1. Group (group E) in which 100 μg of the obtained milk protein fraction was administered per kg body weight of the rat (group E), group (F group) in which the degradation product of the milk protein fraction obtained in Example 3 was administered at 10 μg per kg of body weight of the rat, Example The degradation product of the milk protein fraction obtained in 3 was divided into 7 test groups (n = 6) in a group (group G) administered with 100 μg / kg of rat body weight, and each was administered once daily with a sonde for 10 weeks. It was. Regarding the amount of collagen in the skin, the rat dermis was treated according to the method of Nimni et al. (See Arch. Biochem. Biophys., Page 292, 1967), and then the amount of hydroxyproline contained in the soluble fraction was measured. Hydroxyproline is a special amino acid contained only in collagen and accounts for about 10% of all amino acids constituting collagen, so that the amount of collagen can be estimated (see Takashi Asano et al., Bio Industry, p. 12, 2001). The results are shown in Table 1.
これによると、１０週間後の可溶性画分中ヒドロキシプロリン量は、Ａ群に比べ、Ｂ群、Ｃ群、Ｄ群、Ｅ群、Ｆ群及びＧ群で有意に高い値を示した。また、実施例１で得られた乳タンパク質画分及び実施例３で得られた乳タンパク質画分の分解物は、参考例１で得られた乳タンパク質画分に比べ、約２倍の効果があることがわかった。このことから、本発明の乳タンパク質画分または乳タンパク質画分の分解物には皮膚コラーゲン産生促進作用があることが明らかとなり、皮膚コラーゲン産生促進剤として有用であることが示された。また、この皮膚コラーゲン産生促進作用は乳タンパク質画分または乳タンパク質画分の分解物をラット体重１ｋｇ当たり最低１０μｇ投与した場合に認められることが明らかとなった。 According to this, the amount of hydroxyproline in the soluble fraction after 10 weeks was significantly higher in the B group, the C group, the D group, the E group, the F group and the G group than in the A group. In addition, the milk protein fraction obtained in Example 1 and the degradation product of the milk protein fraction obtained in Example 3 were about twice as effective as the milk protein fraction obtained in Reference Example 1. I found out. This revealed that the milk protein fraction of the present invention or a degradation product of the milk protein fraction has a skin collagen production promoting action, and was shown to be useful as a skin collagen production promoter. It was also revealed that this skin collagen production promoting action was observed when a milk protein fraction or a degradation product of the milk protein fraction was administered at least 10 μg per kg body weight of the rat.
表２に示す配合で、皮膚コラーゲン産生促進剤を配合した飲料を常法により製造した。製造した飲料の風味は良好で、常温１年間保存によっても風味が劣化することはなく、沈殿等の問題もなかった。 The drink which mix | blended the skin collagen production promoter with the mixing | blending shown in Table 2 was manufactured by the conventional method. The flavor of the manufactured beverage was good, and the flavor did not deteriorate even after storage at room temperature for 1 year, and there was no problem such as precipitation.
表３に示す配合のドウを常法により作製し、成形した後、焙焼して皮膚コラーゲン産生促進剤を配合したビスケットを製造した。 A dough having the composition shown in Table 3 was prepared and molded by a conventional method, and then baked to produce a biscuit containing a skin collagen production promoter.
表４に示す配合で、皮膚コラーゲン産生促進剤を常法により製造した。 With the formulation shown in Table 4, a skin collagen production promoter was produced by a conventional method.
表５に示した組成で各成分を混合し、乳化温度85℃で乳化して、皮膚コラーゲン産生促進剤を配合したプロセスチーズを調製した。 Each component was mixed with the composition shown in Table 5, emulsified at an emulsification temperature of 85 ° C., and processed cheese containing a skin collagen production promoter was prepared.
［試験例２］
実施例２で得られた乳タンパク質画分（実施例品２）及び実施例４で得られた乳タンパク質画分の分解物（実施例品４）について、正常ヒト線維芽細胞株〔白人女性の皮膚より採取されたＣＣＤ４５ＳＫ（ＡＴＣＣＲＬ １５０６）〕を用いた実験により皮膚コラーゲン産生促進作用を調べた。１０容量％ウシ胎児血清（以下ＦＢＳと略記）含有変法イーグル培地（ＭＥＭ、１０‐１０１、大日本製薬社製）を用いて、正常ヒト線維芽細胞株を４×１０４個／ウエル／０．４ｍｌとなるように２４ウエルプレートに播種して、５％炭酸ガス、飽和水蒸気下、３７℃で２４時間培養した後、０．６容量％ＦＢＳ含有ＭＥＭ培地に置換した。そして、実施例２で得られた乳タンパク質画分（実施例品２）及び実施例４で得られた乳タンパク質画分の分解物（実施例品４）を、各ウエルに０．１容量％となるように添加（ｎ＝６）して、２４時間培養した後、β−アミノプロピオニトリルを５０μｇ／ｍｌ、トリチウム−Ｌ−プロリンを１μＣｉ／ｍｌとなるように添加して、さらに２４時間培養して培養液を得た。このようにして得られた培養液より、Ｗｅｂｓｔｅｒらの方法（Ａｎａｌｙｔｉｃａｌ Ｂｉｏｃｈｅｍｉｓｔｒｙ，２２０頁，１９７９年 参照）に従いコラーゲン画分を分画し、コラーゲン画分に取り込まれた放射能を測定した。なお、対照として、乳タンパク質画分及び乳タンパク質画分の分解物を添加しないで同様の試験を行った。その結果を表６に示す。
[Test Example 2]
For the milk protein fraction obtained in Example 2 (Example Product 2) and the degradation product of the milk protein fraction obtained in Example 4 (Example Product 4), normal human fibroblast cell line [white female Skin collagen production promoting action was examined by an experiment using CCD45SK (ATCCRL 1506)] collected from the skin. Using a modified Eagle's medium (MEM, 10-101, manufactured by Dainippon Pharmaceutical Co., Ltd.) containing 10% by volume fetal bovine serum (hereinafter abbreviated as FBS), 4 × 10 4 normal human fibroblast cell lines / well / 0 After seeding in a 24-well plate so as to be 4 ml and culturing at 37 ° C. under 5% carbon dioxide gas and saturated steam for 24 hours, the medium was replaced with a 0.6 volume% FBS-containing MEM medium. Then, the milk protein fraction obtained in Example 2 (Example Product 2) and the degradation product of the milk protein fraction obtained in Example 4 (Example Product 4) were added to each well in an amount of 0.1% by volume. (N = 6) and culturing for 24 hours, then adding β-aminopropionitrile to 50 μg / ml and tritium-L-proline to 1 μCi / ml, and further for 24 hours Culture was obtained by culturing. The collagen fraction was fractionated from the culture solution thus obtained according to the method of Webster et al. (See Analytical Biochemistry, page 220, 1979), and the radioactivity incorporated into the collagen fraction was measured. As a control, the same test was performed without adding the milk protein fraction and the degradation product of the milk protein fraction. The results are shown in Table 6.
これによると、乳タンパク質画分及び乳タンパク質画分の分解物を添加した群は、乳タンパク質画分及び乳タンパク質画分の分解物を添加していない群（対照）に比べていずれも２倍以上のコラーゲン産生促進能を示した。このことから、本発明の乳タンパク質画分及び乳タンパク質画分の分解物には、皮膚線維芽細胞に働きかけ、コラーゲン産生を促進する作用があることが明らかとなり、皮膚コラーゲン産生促進剤として有用であることが示された。 According to this, the milk protein fraction and the group to which the degradation product of the milk protein fraction was added were twice as much as the group to which the milk protein fraction and the degradation product of the milk protein fraction were not added (control). The above collagen production promoting ability was demonstrated. This reveals that the milk protein fraction and the degradation product of the milk protein fraction of the present invention have an action of acting on dermal fibroblasts and promoting collagen production, and are useful as a skin collagen production promoter. It was shown that there is.
表７に示す配合の化粧水を常法により製造した。 A lotion having the composition shown in Table 7 was produced by a conventional method.
表８に示す配合のクリームを常法により製造した。 A cream having the composition shown in Table 8 was produced by a conventional method.
［試験例３］
実施例９で得られた化粧水及び実施例１０で得られたクリームを用いて、実使用テストを行った。比較品としては、乳タンパク質画分及び乳タンパク質画分の分解物を除いた以外は実施例９及び１０と同じ配合のものを用いた。顔面のたるみや小ジワが認められる乾燥肌を有する成人女子２０人を、それぞれ１０人ずつ無作為に２群（Ａ、Ｂ群）に、また、手に肌荒れが認められる女子２０人を、それぞれ１０人ずつ無作為に２群（Ｃ、Ｄ群）に分け、Ａ群の顔面には本発明品の化粧水２ｇを、Ｂ群の顔面には比較品の化粧水２ｇを、Ｃ群の手指には本発明品のクリーム２ｇを、Ｄ群の手指には比較品のクリーム２ｇを、それぞれ１日２回通常の使用状態と同様に１０日間塗布してもらった。
[Test Example 3]
Using the lotion obtained in Example 9 and the cream obtained in Example 10, an actual use test was conducted. As a comparative product, the same formulation as in Examples 9 and 10 was used except that the milk protein fraction and the degradation product of the milk protein fraction were excluded. Twenty adult girls with dry skin with sagging and fine wrinkles on the face, each with 10 people randomly divided into 2 groups (Groups A and B), and 20 girls with rough skin on the hands, 10 people randomly divided into 2 groups (Group C, D), 2g of the product of the present invention was applied to the face of Group A, 2g of the comparison product was applied to the face of Group B, and fingers of Group C 2 g of the product of the present invention and 2 g of the comparative product were applied to the fingers of group D twice a day for 10 days in the same manner as in normal use.
表９より、本発明品の化粧水は、比較品の化粧水に比べて、乾燥感の改善、肌荒れ等の改善が顕著であり、皮膚コラーゲン産生促進効果に優れていることが明らかとなった。また、本発明品のクリームについても、比較品のクリームに比べて、乾燥感の改善、肌荒れに顕著な改善がみられ、肌荒れ等の自然増悪抑制効果を有することが明らかとなった。 From Table 9, it was clarified that the skin lotion of the product of the present invention is significantly improved in dry feeling, rough skin, etc., and excellent in promoting skin collagen production, compared to the skin lotion of the comparative product. . In addition, the cream of the present invention also has an improvement in dry feeling and a marked improvement in rough skin, as compared with the comparative cream, and has been found to have an effect of suppressing natural deterioration such as rough skin.
Claims (6)
（ａ）乳由来であること。
（ｂ）ソディウムドデシルサルフェート−ポリアクリルアミドゲル（SDS-PAGE）電気泳動で、分子量７５，０００から８０，０００ダルトンの範囲のタンパク質を含有する画分であること。
（ｃ）構成アミノ酸組成中に塩基性アミノ酸を１３から１５重量％含有し、かつ、塩基性アミノ酸／酸性アミノ酸比が０．５から０．７の範囲であること。 A skin collagen production promoter comprising a milk protein fraction having the following characteristics (a) to (c) as an active ingredient.
(A) It is derived from milk.
(B) A fraction containing a protein having a molecular weight in the range of 75,000 to 80,000 daltons by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE).
(C) The basic amino acid is contained in the constituent amino acid composition in an amount of 13 to 15% by weight, and the basic amino acid / acidic amino acid ratio is in the range of 0.5 to 0.7.
（ａ）乳由来であること。
（ｂ）ソディウムドデシルサルフェート−ポリアクリルアミドゲル（SDS-PAGE）電気泳動で、分子量７５，０００から８０，０００ダルトンの範囲のタンパク質を含有する画分であること。
（ｃ）構成アミノ酸組成中に塩基性アミノ酸を１３から１５重量％含有し、かつ、塩基性アミノ酸／酸性アミノ酸比が０．５から０．７の範囲であること。 A method for promoting the production of skin collagen by orally ingesting a milk protein fraction having the following characteristics (a) to (c) or more at a dose of 10 μg or more per day or 0.001 to 2% by weight.
(A) It is derived from milk.
(B) A fraction containing a protein having a molecular weight in the range of 75,000 to 80,000 daltons by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE).
(C) The basic amino acid is contained in the constituent amino acid composition in an amount of 13 to 15% by weight, and the basic amino acid / acidic amino acid ratio is in the range of 0.5 to 0.7.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003144095A (en) * | 2001-11-08 | 2003-05-20 | Snow Brand Milk Prod Co Ltd | Skin care preparation |
| WO2004098632A1 (en) * | 2003-05-07 | 2004-11-18 | Snow Brand Milk Products Co., Ltd. | Skin collagen production promoter |
| JP2007246413A (en) * | 2006-03-14 | 2007-09-27 | Snow Brand Milk Prod Co Ltd | Composition containing milk-originated basic protein |
| WO2009057281A1 (en) * | 2007-11-01 | 2009-05-07 | Snow Brand Milk Products Co., Ltd. | Food material for promoting the differentiation of osteoblast and inhibiting the differentiation of osteoclast |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003144095A (en) * | 2001-11-08 | 2003-05-20 | Snow Brand Milk Prod Co Ltd | Skin care preparation |
| WO2004098632A1 (en) * | 2003-05-07 | 2004-11-18 | Snow Brand Milk Products Co., Ltd. | Skin collagen production promoter |
| JP2007246413A (en) * | 2006-03-14 | 2007-09-27 | Snow Brand Milk Prod Co Ltd | Composition containing milk-originated basic protein |
| WO2009057281A1 (en) * | 2007-11-01 | 2009-05-07 | Snow Brand Milk Products Co., Ltd. | Food material for promoting the differentiation of osteoblast and inhibiting the differentiation of osteoclast |
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