JP5722282B2 - Skin improving agent and skin improving method - Google Patents

Skin improving agent and skin improving method Download PDF

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JP5722282B2
JP5722282B2 JP2012142862A JP2012142862A JP5722282B2 JP 5722282 B2 JP5722282 B2 JP 5722282B2 JP 2012142862 A JP2012142862 A JP 2012142862A JP 2012142862 A JP2012142862 A JP 2012142862A JP 5722282 B2 JP5722282 B2 JP 5722282B2
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ols3059
thermophilus ols3059
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宏 狩野
宏 狩野
晃幸 野間
晃幸 野間
秀二 池上
秀二 池上
伊藤　裕之
裕之 伊藤
佳久平 伊澤
佳久平 伊澤
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Meiji Co Ltd
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Description

本発明は、皮膚改善効果及び／又は治療効果が高い組成物と、これを用いた飲食物及び発酵乳に関し、特に、製造特性が良い乳酸菌を含有する組成物及び発酵乳に関する。  The present invention relates to a composition having a high skin improvement effect and / or therapeutic effect, food and drink and fermented milk using the same, and particularly to a composition containing lactic acid bacteria having good production characteristics and fermented milk.

皮膚の改善や治療等を目的とした組成物や飲食品に、乳酸菌やその培養物を含有したものがある。これら組成物や飲食品に関する先行技術として、特定の乳酸菌を用いたアトピー性皮膚炎の抑制剤及び食品（特許文献１）、特定の乳酸菌の培養物を用いた皮膚改善効果を有する保湿剤、及び肌荒れや乾燥肌の予防・治療に有効であり、肌（皮膚）に「つや」や「はり」を与える化粧料組成物（特許文献２）、特定の乳酸菌やその培養物を皮膚（肌）の免疫系のバランスを保つために使用すること及び乳酸菌やその培養物を含有した食品等（特許文献３）、コラーゲンペプチドやセラミドと乳酸菌を組み合わせて用いることにより、肌（皮膚）の改善に加え、便通改善、疲労回復、肩こりの軽減等も併せて期待できる美容食品（特許文献４）等がある。  Some compositions and foods and drinks for the purpose of improving and treating the skin contain lactic acid bacteria and their cultures. As a prior art related to these compositions and foods and drinks, an atopic dermatitis inhibitor using a specific lactic acid bacterium and food (Patent Document 1), a moisturizer having a skin improvement effect using a culture of a specific lactic acid bacterium, and A cosmetic composition (Patent Document 2) that is effective in preventing and treating rough skin and dry skin, and gives the skin (skin) “gloss” and “harness”, and specific lactic acid bacteria and cultures of the skin (skin) In addition to improving the skin (skin) by using in order to maintain the balance of the immune system and using a combination of lactic acid bacteria and foods containing the culture (Patent Document 3), collagen peptides or ceramide and lactic acid bacteria, There are beauty foods (Patent Document 4) that can be expected to improve bowel movements, recovery from fatigue, reduction of stiff shoulders, and the like.

前記した通り、乳酸菌やその培養物に、皮膚改善効果や治療効果があることを見いだし、それを産業上で応用することが従来から期待されていることは事実である。幾つかの具体的な研究が行われており、実際に製品化されたものも存在すると考えられる。  As described above, it is a fact that lactic acid bacteria and their cultures have been found to have a skin improvement effect and a therapeutic effect and are expected to be applied in industry. Several specific studies have been carried out, and it is thought that some products have actually been commercialized.

しかしながら、従来までの研究では、乳酸菌と皮膚（肌）との関係、あるいは乳酸菌にコラーゲンペプチドやセラミド等を添加した組成物と皮膚（肌）との関係について検討が不十分であった。そのため、乳酸菌や発酵乳による皮膚改善効果等について科学的な根拠が乏しい状態であった。  However, in previous studies, the relationship between lactic acid bacteria and skin (skin), or the relationship between a composition obtained by adding collagen peptide, ceramide, etc. to lactic acid bacteria and the skin (skin) was insufficient. For this reason, the scientific basis for the skin improvement effect by lactic acid bacteria and fermented milk has been poor.

また、皮膚改善効果等を持つ従来までの乳酸菌では、発酵乳を製造する際に、カードを形成しなかったり、カードを形成するまでの時間が大幅に長くなったりしていた。この場合には、皮膚改善効果等を持つが、発酵乳の製造特性が悪い乳酸菌と、カードを形成するための製造特性が良い乳酸菌とを別に管理したり、発酵時間が長くなることで、製造時間の全体が長くなったりしていた。このとき、皮膚改善効果等を持つ従来までの乳酸菌は生菌ではなく、死菌であったり、耐熱性の高い、限られた菌体であったりした。つまり、皮膚改善効果等を持つ従来までの乳酸菌は、発酵乳の工業的な大量生産（商業的な生産）等には適していなかった。  Further, in the conventional lactic acid bacteria having a skin improvement effect and the like, when producing fermented milk, the card is not formed or the time until the card is formed is significantly increased. In this case, lactic acid bacteria that have a skin improvement effect, etc. but have poor production characteristics of fermented milk, and lactic acid bacteria that have good production characteristics for forming a card, can be manufactured by prolonging fermentation time. The whole time was getting longer. At this time, conventional lactic acid bacteria having a skin improvement effect and the like were not viable bacteria, but dead bacteria or limited bacterial bodies with high heat resistance. That is, the conventional lactic acid bacteria having skin improvement effects and the like are not suitable for industrial mass production (commercial production) of fermented milk.

例えば、皮膚改善効果等を持つと言われている従来までの乳酸菌を用いて発酵乳を製造しようとすると、概略で次の様な製造工程を必要とする。すなわち、（１）皮膚改善効果等を持つ乳酸菌を単独で培養する。（２）状況に応じて遠心分離法や膜分離法により、その乳酸菌（培養菌体）を所定の濃度まで濃縮する、又は、乳酸菌の保存性を高めるために、培養液を加熱殺菌したり、乾燥したりする。（３）カードを形成する別の乳酸菌と、その濃縮された培養菌体、又は加熱殺菌や乾燥されたものとを発酵前の調合乳へ添加し、混合培養する。  For example, when it is going to manufacture fermented milk using the conventional lactic acid bacteria said to have the skin improvement effect etc., the following manufacturing processes are required roughly. That is, (1) lactic acid bacteria having skin improvement effects and the like are cultured alone. (2) Concentrate the lactic acid bacteria (cultured cells) to a predetermined concentration by centrifugation or membrane separation depending on the situation, or heat sterilize the culture solution in order to enhance the storage stability of the lactic acid bacteria, Or dry. (3) Another lactic acid bacterium forming a card and its concentrated cultured microbial cell, or heat-sterilized or dried product are added to the pre-fermented formula milk and mixed and cultured.

これらの製造工程は管理が複雑であり、製造費用も製造時間も増大し、雑菌が混入する可能性も高い。また、嗜好性に優れた風味の良い発酵乳を得ることも難しい。  These manufacturing processes are complicated to manage, increase manufacturing costs and manufacturing time, and have a high possibility of contamination. It is also difficult to obtain a savory fermented milk with excellent palatability.

特開２０００−０９５６９７号公報Japanese Patent Laid-Open No. 2000-095597 特開２００３−０８１８０８号公報JP 2003-081808 A 特表２００４−５１０７４０号公報Japanese translation of PCT publication No. 2004-510740 特開２００４−２５４６３２号公報JP 2004-254632 A

本発明は、上記従来技術の課題点を鑑みてなされたもので、天然物由来で安全性が高く、皮膚改善効果及び／又は治療効果が高い組成物、皮膚改善及び／又は治療の用途に適した組成物と、当該組成物を用いた、皮膚改善効果及び／又は治療効果が高い飲食品及び発酵乳、特に、製造特性が良い乳酸菌を含有する組成物及び発酵乳を提供することを目的とする。  The present invention has been made in view of the above-mentioned problems of the prior art, and is suitable for use in a composition, skin improvement and / or treatment that is derived from a natural product and has high safety and high skin improvement effect and / or treatment effect. It is an object of the present invention to provide a composition and a fermented milk and fermented milk having high skin improvement effect and / or therapeutic effect using the composition, in particular, a composition and fermented milk containing lactic acid bacteria having good production characteristics. To do.

本発明者らは、上記課題に鑑み、鋭意研究を重ねた結果、発酵乳の調製に用いる乳酸菌から皮膚改善効果や治療効果が高いものを選抜する目的で、in vitro 試験を行うことにより、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）に特別、皮膚改善効果及び／又は治療効果が高いとの知見を得て、本発明を完成するに至った。  As a result of intensive research in view of the above problems, the present inventors conducted an in vitro test for the purpose of selecting a lactic acid bacterium used for the preparation of fermented milk with a high skin improvement effect and a therapeutic effect. The present invention was completed by obtaining knowledge that Filus bacterium OLS3059 (Streptococcus thermophilus OLS3059) has a special skin improvement effect and / or high therapeutic effect.

すなわち、請求項１に係る発明は、
サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、
前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０７ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ以上、及びセラミドを３００μｇ以上含有し、
肌の弾性力を増加させて肌のはりを改善させると共に、肌のキメ密度を増加させて肌のキメを改善させることを特徴とする皮膚改善剤
である。 That is, the invention according to claim 1
A skin improver comprising Streptococcus thermophilus OLS3059 (Accession Number: FERM P-15487) and / or a culture thereof as an active ingredient,
The compounding concentration of the aforementioned Streptococcus thermophilus OLS3059 (Accession number: FERM P-15487) is 85 × 10 7 cfu / g or more , collagen peptide is 1000 mg or more, and ceramide is 300 μg or more,
A skin improver characterized by improving the skin elasticity by increasing the elasticity of the skin and improving the texture of the skin by increasing the density of the skin texture.

請求項２に係る発明は、
サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物、並びにブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）（受託番号：ＦＥＲＭ Ｐ−１７２２７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、
前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０７ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ以上、及びセラミドを３００μｇ以上含有し、
肌の弾性力を増加させて肌のはりを改善させると共に、肌のキメ密度を増加させて肌のキメを改善させることを特徴とする皮膚改善剤
である。 The invention according to claim 2
Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) and / or its culture, and Bulgarian bacteria OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) (Accession number: FERM P-17227) and / Or a skin improvement agent comprising a culture thereof as an active ingredient,
The compounding concentration of the above-mentioned Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) is 85 × 10 7 cfu / g or more , collagen peptide is 1000 mg or more, and ceramide is 300 μg or more,
A skin improver characterized by improving the skin elasticity by increasing the elasticity of the skin and improving the texture of the skin by increasing the density of the skin texture.

請求項３に係る発明は、
サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０ ７ ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、前記皮膚改善剤の摂取により整腸改善効果及び／又は治療効果が認められるヒトの皮膚の乾皮・痂皮形成、発赤・出血、組織脱落・擦り傷、浮腫、掻痒のうち、いずれか１項目以上の改善に用いられる皮膚改善剤
である。 The invention according to claim 3
A skin ameliorating agent comprising Streptococcus thermophilus OLS3059 (Accession number: FERM P-15487) and / or a culture thereof as an active ingredient, wherein the Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) ( (Contract number: FERM P-15487) is 85 × 10 7 cfu / g or more, collagen peptide is 1000 mg / 90 g or more, and ceramide is 300 μg / 90 g or more. A skin improvement agent that is used to improve at least one of dry skin / scab formation, redness / bleeding, tissue loss / abrasion, edema, pruritus in human skin where improvement and / or treatment effects are observed. is there.

請求項４に係る発明は、
サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物、並びにブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）（受託番号：ＦＥＲＭ Ｐ−１７２２７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０ ７ ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、前記皮膚改善剤の摂取により整腸改善効果及び／又は治療効果が認められるヒトの皮膚の乾皮・痂皮形成、発赤・出血、組織脱落・擦り傷、浮腫、掻痒のうち、いずれか１項目以上の改善に用いられる皮膚改善剤
である。 The invention according to claim 4
Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) and / or its culture, and Bulgarian bacteria OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) (Accession number: FERM P-17227) and / Or a skin improvement agent comprising a culture thereof as an active ingredient, wherein the compounding concentration of the above-mentioned Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession Number: FERM P-15487) is 85 × 10 7 cfu / g or more, collagen peptide 1000 mg / 90 g or more and ceramide 300 μg / 90 g or more At least one of the following: formation, redness / bleeding, tissue loss / abrasion, edema, pruritus A skin improving agent used in the good.

請求項５に係る発明は、
サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物、並びにブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）（受託番号：ＦＥＲＭ Ｐ−１７２２７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、
前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０ ７ ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、
肌の弾性力を増加させて肌のはりを改善させると共に、肌のキメ密度を増加させて肌のキメを改善させることを特徴とする皮膚改善剤（ただし、発酵乳の態様からなる皮膚改善剤を除く）。
である。 The invention according to claim 5
Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) and / or its culture, and Bulgarian bacteria OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) (Accession number: FERM P-17227) and / Or a skin improvement agent comprising a culture thereof as an active ingredient ,
The thermophilus bacteria OLS3059 (Streptococcus thermophilus OLS3059) (accession number: FERM P-15487) containing formulations concentration is at 85 × 10 7 cfu / g or more, the collagen peptide 1000 mg / 90 g or more, and ceramide 300 [mu] g / 90 g or more And
A skin improving agent (however, a skin improving agent consisting of a fermented milk form) that improves the skin elasticity by increasing the elasticity of the skin and improving the texture of the skin by increasing the density of the skin except for).
It is.

請求項６に係る発明は、
サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物、並びにブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）（受託番号：ＦＥＲＭ Ｐ−１７２２７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０ ７ ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、前記皮膚改善剤の摂取により整腸改善効果及び／又は治療効果が認められるヒトの皮膚の乾皮・痂皮形成、発赤・出血、組織脱落・擦り傷、浮腫、掻痒のうち、いずれか１項目以上の改善に用いられる皮膚改善剤（ただし、発酵乳の態様からなる皮膚改善剤を除く）
である。 The invention according to claim 6
Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) and / or its culture, and Bulgarian bacteria OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) (Accession number: FERM P-17227) and / Or a skin improvement agent comprising a culture thereof as an active ingredient , wherein the compounding concentration of the above-mentioned Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession Number: FERM P-15487) is 85 × 10 7 cfu / g or more, collagen peptide 1000 mg / 90 g or more and ceramide 300 μg / 90 g or more formation, redness, bleeding, tissue falling off, abrasions, swelling, of the itching, any one or more items of Good skin improvement agent used in (except for skin improvement agents consisting aspects of fermented milk)
It is.

請求項７に係る発明は、

食品に配合することを目的とした、請求項１乃至６のいずれか一項に記載の皮膚改善剤
である。 The invention according to claim 7 provides:

It is a skin improvement agent as described in any one of Claims 1 thru | or 6 aiming at mix | blending with foodstuffs .

請求項８に係る発明は、
食品に配合して発酵させることを目的とした、請求項１乃至６のいずれか一項に記載の皮膚改善剤
である。 The invention according to claim 8 provides:
It is a skin improvement agent as described in any one of Claims 1 thru | or 6 aiming at mix | blending with food and making it ferment .

なお、本発明において「皮膚改善効果及び／又は治療効果」とは、皮膚や肌のつや、はり、くすみ、しみ、たるみ、毛穴の目立ち、キメ、しわ、乾燥具合、べたつき、透明感、赤み、ファンデーションのノリ、むくみ、くまの目立ち、皮疹、保湿、色素沈着のうち、少なくとも１つ以上の状態について改善の効果があるものをいい、「皮膚改善及び／又は治療」とは、皮膚や肌のつや、はり、くすみ、しみ、たるみ、毛穴の目立ち、キメ、しわ、乾燥具合、べたつき、透明感、赤み、ファンデーションのノリ、むくみ、くまの目立ち、皮疹、保湿、色素沈着のうち、少なくとも１つ以上の状態について改善することをいう。また、「皮膚改善及び／治療」には、アトピー性皮膚炎を始め、各種アレルギー性皮膚炎による肌症状の改善や発症抑制も含む。また「皮膚改善用及び／又は治療用」とは、前記の皮膚改善効果及び／又は治療効果を発揮させることを目的として用いられることをいい、特に、前記の皮膚改善効果及び／又は治療効果を発揮させる用途に適していることをいう。  In the present invention, the “skin improving effect and / or therapeutic effect” refers to skin and skin gloss, beam, dullness, blotch, sagging, conspicuous pores, texture, wrinkles, dryness, stickiness, transparency, redness, It means that there is an improvement effect on at least one of the following conditions: “skin improvement and / or treatment” of skin, skin, skin, skin swelling, moisturization, and pigmentation. At least one of gloss, beam, dullness, blotch, sagging, pore conspicuousness, texture, wrinkle, dryness, stickiness, transparency, redness, foundation glue, swelling, bear noticeable, skin rash, moisturizing, pigmentation It means to improve the above situation. In addition, “skin improvement and / or treatment” includes improvement and suppression of onset of skin symptoms due to various allergic dermatitis, including atopic dermatitis. The term “for skin improvement and / or treatment” refers to being used for the purpose of exerting the above skin improvement effect and / or treatment effect, and in particular, the above skin improvement effect and / or treatment effect. It means that it is suitable for the application to be demonstrated.

本発明において「ブルガリア菌（Lactobacillus delbrueckii subspecies bulgaricus）」は、発酵乳の調製において、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）と組み合わせて、スターターに用いることで、カードを形成する能力を持つ乳酸菌を全て含むものであり、例えば、明治乳業株式会社製のプレーンヨーグルト、ハードヨーグルト、ソフトヨーグルトから単離して得られる乳酸菌がある。  In the present invention, “Lactobacillus delbrueckii subspecies bulgaricus” is a combination of Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) in the preparation of fermented milk. Examples include lactic acid bacteria obtained by isolation from plain yogurt, hard yogurt, and soft yogurt manufactured by Meiji Dairies.

本発明においてサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）は、独立行政法人 産業技術総合研究所 特許生物寄託センターに受領番号：FERM P-15487（識別のための表示： Streptococcus thermophilus OLS3059、寄託日（受領日）：平成
8年 2月 29日）で寄託されているものである。In the present invention, Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) is received by the National Institute of Advanced Industrial Science and Technology, Patent Biological Deposit Center. : Heisei
(February 29, 2008).

また、本発明においてブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）は、独立行政法人 産業技術総合研究所 特許生物寄託センターに受領番号：FERM P-17227（識別のための表示： Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1、寄託日（受領日）：平成 11年 2月 19日）で寄託されているものである。  In addition, in the present invention, the Bulgarian bacterium OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) is received at the Patent Organism Depositary, National Institute of Advanced Industrial Science and Technology. subspecies bulgaricus OLL1073R-1, Deposit date (date of receipt: February 19, 1999).

本発明は皮膚改善及び／又は治療に用いられるサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）の用途を提供することができる。  The present invention can provide a use of Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) used for skin improvement and / or treatment.

本発明によれば、天然物由来で安全性が高く、皮膚改善効果及び／又は治療効果が高い組成物、皮膚改善及び／又は治療の用途に適した組成物と、当該組成物を用いた、皮膚改善効果及び／又は治療効果が高い飲食品及び発酵乳、特に、製造特性が良い乳酸菌を含有する組成物及び発酵乳を提供することができる。  According to the present invention, a composition derived from a natural product and having high safety, a skin improvement effect and / or a high therapeutic effect, a composition suitable for use in skin improvement and / or treatment, and the composition are used. It is possible to provide a food and drink and fermented milk having a high skin improvement effect and / or therapeutic effect, in particular, a composition and fermented milk containing lactic acid bacteria having good production characteristics.

本発明によれば、整腸（便通）改善効果及び／又は治療効果の高かったヒトに対して、皮膚改善効果及び／又は治療効果が高い発酵乳とその製造方法を提供することができる。  ADVANTAGE OF THE INVENTION According to this invention, fermented milk with a high skin improvement effect and / or therapeutic effect and its manufacturing method can be provided with respect to the human whose intestinal regulation (fecal bowel) improvement effect and / or therapeutic effect were high.

蒸留水投与群、Lactobacillus rhamnosus ATCC 53103 投与群、Streptococcus thermophilus OLS3059 投与群及び皮膚炎非惹起群における試験期間中の皮膚炎発症スコアの推移（平均±標準偏差で表記した。**P < 0.01、*P < 0.05、Dunnett の多重比較）を示したグラフである。Transition of dermatitis development score during the test period in the distilled water administration group, Lactobacillus rhamnosus ATCC 53103 administration group, Streptococcus thermophilus OLS3059 administration group and non-dermatitis induction group (expressed as mean ± standard deviation. ** P <0.01, * P <0.05, Dunnett's multiple comparison). 蒸留水投与群、Lactobacillus rhamnosus ATCC 53103 投与群、Streptococcus thermophilus OLS3059 投与群及び皮膚炎非惹起群における15日後（day 15）の血清中の総IgE 濃度（平均±標準偏差で表記した。**P < 0.01、Dunnett の多重比較）を示したグラフである。Total IgE concentration in serum after 15 days (day 15) in the distilled water administration group, Lactobacillus rhamnosus ATCC 53103 administration group, Streptococcus thermophilus OLS3059 administration group and non-dermatitis induction group (expressed as mean ± standard deviation. ** P < It is a graph showing 0.01, Dunnett's multiple comparison). 蒸留水投与群、Lactobacillus bulgaricus OLL1073R-1 投与群及びStreptococcus thermophilus OLS3059 投与群における試験期間中の皮膚炎発症スコアの推移（平均±標準偏差で表記した。**P < 0.01、*P < 0.05、Dunnett の多重比較）を示したグラフである。Changes in dermatitis development score during the test period in the distilled water administration group, Lactobacillus bulgaricus OLL1073R-1 administration group and Streptococcus thermophilus OLS3059 administration group (expressed as mean ± standard deviation. ** P <0.01, * P <0.05, Dunnett Is a graph showing a multiple comparison). 蒸留水投与群、Lactobacillus bulgaricus OLL1073R-1 投与群及びStreptococcus thermophilus OLS3059 投与群における15日後（day 15）の血清中の総IgE 濃度（平均±標準偏差で表記した。**P < 0.01、Dunnett の多重比較）を示したグラフである。Total IgE concentration in serum after 15 days (day 15) in the distilled water administration group, Lactobacillus bulgaricus OLL1073R-1 administration group and Streptococcus thermophilus OLS3059 administration group (expressed as mean ± standard deviation. ** P <0.01, Dunnett's multiple It is the graph which showed (comparison). Lactobacillus bulgaricus OLL1073R-1とStreptococcus thermophilus OLS3059で調製した発酵物の投与群、Lactobacillus delbrueckii subspecies bulgaricus MEP1705601とStreptococcus thermophilus MEP1705601で調製した発酵物の投与群、未発酵物の投与群及び皮膚炎非惹起かつ未発酵物の投与群における試験期間中の皮膚炎発症スコアの推移（平均±標準偏差で表記した。**P < 0.01、*P < 0.05、Dunnett の多重比較）を示したグラフである。Lactobacillus bulgaricus OLL1073R-1 and Streptococcus thermophilus OLS3059 fermented product administration group, Lactobacillus delbrueckii subspecies bulgaricus MEP1705601 and Streptococcus thermophilus MEP1705601 fermented product administration group, unfermented product administration group and non-fermentative and non-fermentative 6 is a graph showing the transition of the dermatitis onset score during the test period (expressed as mean ± standard deviation. ** P <0.01, * P <0.05, Dunnett's multiple comparison) in the administration group. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、被験者の皮膚（肌）の弾力性を示したグラフである。It is the graph which showed the elasticity of the test subject's skin (skin) which made the test milk the fermented milk prepared with the thermophilus OLS3059 (Streptococcus thermophilus OLS3059). サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、被験者の皮膚（肌）のキメ密度を示したグラフである。It is the graph which showed the texture density of the test subject's skin (skin) which used fermented milk prepared by the thermophilus OLS3059 (Streptococcus thermophilus OLS3059) as a test food. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、被験者の総皮疹数の観察結果を示したグラフである。It is the graph which showed the observation result of the test subject's total skin eruption which made fermented milk prepared with thermophilus OLS3059 (Streptococcus thermophilus OLS3059) into a test meal. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、被験者及び医師による有用性の評価結果を示したグラフである。It is the graph which showed the evaluation result of the usefulness by a test subject and a doctor using the fermented milk prepared by Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) as a test meal. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、「整腸が「１以上」改善された」被験者の皮膚（肌）の弾力性を示したグラフである。It is the graph which showed the elasticity of the skin (skin) of the test subject who used fermented milk prepared by Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) as a test meal, and whose intestinal regulation was improved "1 or more". サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、「整腸が「２以上」改善された」被験者の皮膚（肌）の弾力性を示したグラフである。It is the graph which showed the elasticity of the skin (skin) of the test subject who used fermented milk prepared by Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) as a test meal, and whose intestinal regulation was improved "2 or more". サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、「整腸が「３以上」改善された」被験者の皮膚（肌）の弾力性を示したグラフである。It is the graph which showed the elasticity of the skin (skin) of the test subject who used fermented milk prepared with Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) as a test meal. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、「整腸が「１以上」改善された」被験者の皮膚（肌）のキメ密度を示したグラフである。It is the graph which showed the texture density of the skin (skin) of the test subject who used fermented milk prepared with Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) as a test meal. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、「整腸が「２以上」改善された」被験者の皮膚（肌）のキメ密度を示したグラフである。It is the graph which showed the texture density of the skin (skin) of the test subject who used fermented milk prepared by Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) as a test meal. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）で調製した発酵乳を試験食とした、「整腸が「３以上」改善された」被験者の皮膚（肌）のキメ密度を示したグラフである。It is the graph which showed the texture density of the skin (skin) of the test subject who made fermented milk prepared by Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) the test meal.

本願発明は、皮膚改善及び／又は治療に用いられるサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）の用途を提案するものである。すなわち、本発明者らが鋭意研究を重ねた結果、発酵乳の調製に用いる乳酸菌から皮膚改善効果や治療効果が高いものを選抜する目的で、in vitro 試験を行うことにより、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）に特別、皮膚改善効果及び／又は治療効果が高いとの知見を得て、本発明を完成したものである。  The present invention proposes the use of Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) used for skin improvement and / or treatment. That is, as a result of extensive research conducted by the present inventors, in order to select lactic acid bacteria used for the preparation of fermented milk that have a high skin improvement effect and therapeutic effect, an in vitro test was conducted, and Thermofilus OLS3059 ( Streptococcus thermophilus OLS3059) has specially obtained the knowledge that the skin improving effect and / or therapeutic effect is high, and the present invention has been completed.

次に、本発明の組成物は、皮膚改善用及び／又は治療用の組成物であって、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）及び／又はその培養物を含有するものである。この本発明の皮膚改善用及び／又は治療用の組成物は、天然物由来であるので安全性が高く、更に、皮膚改善効果及び／又は治療効果が高く、これらの用途に適したものである。  Next, the composition of the present invention is a composition for skin improvement and / or treatment, and contains Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) and / or a culture thereof. This composition for skin improvement and / or treatment of the present invention is derived from a natural product and thus has high safety, and further has a high skin improvement effect and / or treatment effect and is suitable for these uses. .

本発明者らが、発酵乳の調製に用いる、カードを形成する能を持った、製造特性の良い乳酸菌から皮膚改善効果及び／又は治療効果が高いものを選抜するため、in vitro 試験を行ったところ、前述したように、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）に特別、皮膚改善効果及び／又は治療効果が高いとの知見を得た。  The present inventors conducted an in vitro test to select a lactic acid bacterium having the ability to form a card and having good production characteristics to prepare a fermented milk and having a high skin improvement effect and / or a therapeutic effect. However, as described above, the present inventors have found that Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) has a special skin improvement effect and / or therapeutic effect.

前記本発明のサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）及び／又はその培養物を含有してなる皮膚改善用及び／又は治療用の組成物は、ブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）及び／又はその培養物を更に含有しているものとすることができる。  The composition for skin improvement and / or treatment comprising the aforementioned thermophilus OLS3059 (Streptococcus thermophilus OLS3059) and / or its culture according to the present invention is a Bulgarian bacterium OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1). ) And / or a culture thereof.

発明者等の実験によれば、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）及び／又はその培養物と、菌体外に粘性多糖類を生産するブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）とを組み合わせた場合にも、皮膚改善効果及び／又は治療効果が高く、これらの用途に適したものであることが認められた。  According to experiments by the inventors, Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) and / or its culture, and Bulgarian OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) producing viscous polysaccharides outside the cell Even when combined with the above, it was confirmed that the skin improvement effect and / or the therapeutic effect was high and suitable for these uses.

なお、サーモフィルス菌 OLS3059は、例えば、ブルガリアヨーグルトLB81（（登録商標）明治乳業株式会社製）に使用されている。  Thermophilus OLS3059 is used, for example, in Bulgarian yogurt LB81 ((registered trademark) Meiji Dairies Co., Ltd.).

前記のサーモフィルス菌 OLS3059及び／又はその培養物、ブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）及び／又はその培養物とは、いずれも、乳酸菌を単離・精製した菌体の他に、菌体を含む培養物、菌体の抽出物、培養物の上清、これらの濃縮液、濃縮物、乾燥物、さらに必要に応じて希釈液、希釈物等であり、培養液、培養物を処理して得られる全ての状態のものが含まれる。  The aforementioned thermophilus OLS3059 and / or its culture, Bulgarian OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) and / or its culture are all in addition to the cells from which lactic acid bacteria have been isolated and purified. In addition, a culture containing microbial cells, an extract of microbial cells, a supernatant of the culture, a concentrated solution, a concentrated product, a dried product, and a diluted solution, a diluted product, etc., if necessary. All the states obtained by processing the object are included.

前記のサーモフィルス菌 OLS3059は、生菌及び死菌の何れでも、皮膚改善効果及び／又は治療効果が高く、皮膚改善及び／又は治療に用いることができる。また、ブルガリア菌OLL1073R-1も、生菌及び死菌の何れでも用いることができる。さらに、サーモフィルス菌
OLS3059も、ブルガリア菌OLL1073R-1も、菌体の培養法、抽出法、分離法、濃縮法、乾燥法、希釈法等は特に限定されない。菌体を培養するための培地には通常、脱脂乳、ホエー、カゼイン等の牛乳蛋白質、糖類、酵母エキス等を含んでおり、培養方法には一般的な各種好気的あるいは嫌気的な方法を適宜、用いることができる。培養温度には例えば、35〜45℃を設定し、培養中には水酸化ナトリウム等のアルカリを用いて、培地のpHを中性から酸性、例えばpHが5〜6程度となるように維持する中和培養法を用いることもできる。このような中和培養法の他に、回分培養法等の任意の培養方法を用いることができ、培養した後には、必要に応じて培養物やその上清を、濃縮、乾燥、希釈等することもできる。さらに、遠心分離法や膜分離法を用いて、培養物の上清と菌体を分離し、菌体を濃縮した状態で、回収することもできる。そして、菌体に超音波処理や酵素処理等を行い、菌体内の成分を抽出したり、培養物やその上清、菌体やその抽出物等を乾燥することもできる。これらは本発明の前記組成物の有効成分として用いることができる。The thermophilus OLS3059 has a high skin improvement effect and / or therapeutic effect in both live and dead bacteria, and can be used for skin improvement and / or treatment. In addition, Bulgarian bacteria OLL1073R-1 can be used as either live or dead bacteria. In addition, thermophilus
Neither OLS3059 nor Bulgarian bacteria OLL1073R-1 is particularly limited in terms of cell culture, extraction, separation, concentration, drying, dilution, and the like. The medium for culturing the cells usually contains milk protein such as skim milk, whey and casein, saccharides, yeast extract, etc., and various general aerobic or anaerobic methods are used for the culture method. It can be used as appropriate. The culture temperature is set to 35 to 45 ° C., for example, and an alkali such as sodium hydroxide is used during the culture to maintain the pH of the medium from neutral to acidic, for example, the pH is about 5 to 6. A neutralization culture method can also be used. In addition to such a neutralization culture method, any culture method such as a batch culture method can be used. After culturing, the culture and its supernatant are concentrated, dried, diluted, etc. as necessary. You can also. Furthermore, the supernatant of the culture and the cells can be separated using a centrifugal separation method or a membrane separation method, and the cells can be collected in a concentrated state. The cells can be subjected to ultrasonic treatment, enzyme treatment, and the like to extract the components in the cells, and the culture, the supernatant thereof, the cells, the extract thereof, and the like can be dried. These can be used as active ingredients of the composition of the present invention.

本発明の組成物は、任意の成分を添加し、常法に従い、皮膚外用剤として用いることができる。例えば、通常の化粧料、医薬品部外、医薬品等に用いられる各種成分、油剤、増粘剤、防腐剤、乳化剤、顔料、pH調整剤、抗酸化剤、香料等を適宜、配合し、クリーム、乳液、化粧料、ファンデーション、ローション、シャンプー等、その目的に応じて任意に用いることができる。  The composition of the present invention can be used as an external preparation for skin according to a conventional method to which optional components are added. For example, various ingredients used in normal cosmetics, quasi-drugs, pharmaceuticals, oils, thickeners, preservatives, emulsifiers, pigments, pH adjusters, antioxidants, fragrances, etc. Emulsions, cosmetics, foundations, lotions, shampoos and the like can be used arbitrarily depending on the purpose.

本発明の飲食品は、前述した本発明の組成物を含有するものである。かかる本発明の飲食品は、皮膚改善効果及び／又は治療効果が高く、これらの用途に適したものである。  The food / beverage products of this invention contain the composition of this invention mentioned above. Such a food or drink of the present invention has a high skin improvement effect and / or therapeutic effect, and is suitable for these uses.

前述した本発明の組成物は、食用として実績のある乳酸菌を有効成分としているため、安全性については全く問題がなく、飲食品、医薬品として、経口的及び／又は非経口的に投与できる。  Since the composition of the present invention described above contains lactic acid bacteria that have been used for food as an active ingredient, there is no safety problem, and it can be administered orally and / or parenterally as a food or drink or a pharmaceutical product.

この場合に、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）の菌体を単独でも用いることができるし、あるいは通常の食餌成分に混合して用いることもできる。また、サーモフィルス菌 OLS3059とブルガリア菌OLL1073R-1の菌体とをそれぞれ単独でも用いることができるし、あるいはこれらを組み合わせたものを通常の食餌成分に混合して用いることもできる。更に、サーモフィルス菌 OLS3059、あるいはサーモフィルス菌 OLS3059とブルガリア菌OLL1073R-1とを組み合わせたものを経口投与剤及び／又は非経口投与剤の製造において用いられている、通常の各種補助剤等と混合して製剤化することもできる。  In this case, the cells of Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) can be used alone, or can be used by mixing with normal dietary ingredients. In addition, the cells of Thermophilus OLS3059 and Bulgarian OLL1073R-1 can be used alone, or a combination of these can be mixed with a normal diet component. Furthermore, Thermophilus OLS3059 or a combination of Thermophilus OLS3059 and Bulgarian OLL1073R-1 is mixed with usual adjuvants used in the production of oral and / or parenteral agents. And can also be formulated.

サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）、あるいはサーモフィルス菌 OLS3059とブルガリア菌OLL1073R-1とを組み合わせたものを通常の食餌成分や、経口投与剤及び／又は非経口投与剤の製造において用いられている通常の各種補助剤等に混合して用いる場合、サーモフィルス菌 OLS3059の添加量（配合量）は、本発明の飲食品を摂取する者の年齢、体重、投与方法等を考慮して適宜、定めることができるが、１０９（10の9乗） cfu／日以上、好ましくは１０１０（10の10乗） cfu／日以上である。Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) or a combination of Thermophilus OLS3059 and Bulgarian OLL1073R-1 is used in the production of normal dietary ingredients and oral and / or parenteral administration When used in combination with various normal adjuvants, the addition amount (formulation amount) of Thermophilus OLS3059 is appropriately determined in consideration of the age, weight, administration method, etc. of the person who takes the food or drink of the present invention. 10 9 (10 9) cfu / day or more, preferably 10 10 (10 10) cfu / day or more.

本発明の飲食品としては、前述した本発明の組成物を含有する飲料（ドリンク）、錠剤（タブレット）等の他に、ビスケット、パン、スポンジケーキ、発酵乳、ヨーグルト、チーズ、バター、マーガリン、クリーム、ゼリー等がある。本発明の飲食品の使用形態、使用方法としては、前述した飲食品に、直接、本発明の組成物を添加する形態、方法がある。また、これにより得られた本発明の飲食品であるヨーグルト、チーズ、バター等を、さらに飲食品に添加する形態、方法もある。  As the food and drink of the present invention, in addition to the beverage (drink), tablet (tablet) and the like containing the composition of the present invention described above, biscuits, bread, sponge cake, fermented milk, yogurt, cheese, butter, margarine, There are cream and jelly. As a usage form and usage method of the food / beverage products of this invention, there exists a form and a method of adding the composition of this invention directly to the food / beverage products mentioned above. There are also forms and methods in which yogurt, cheese, butter, etc., which are food and drink products of the present invention thus obtained, are further added to the food and drink products.

そして、本発明の飲食品は、皮膚改善効果及び／又は治療効果を発揮させることを目的として、通常の飲食品の他に、特定保健用食品、栄養機能食品、健康食品等に用いることができる。  And the food / beverage products of this invention can be used for foods for specific health, foods with functional nutrition, health foods, etc. in addition to normal food / beverage products for the purpose of exerting a skin improvement effect and / or a therapeutic effect. .

さらに、本発明の飲食品は、皮膚改善効果及び／又は治療効果を有するため、皮膚改善及び／又は治療のために用いられる旨の表示を付した飲食品とすることもできる。なお、表示方法としては、飲食品のパッケージへの表示の他に、パンフレットへの掲載や宣伝等も含まれる。  Furthermore, since the food / beverage products of this invention have a skin improvement effect and / or a therapeutic effect, it can also be set as the food / beverage products which attached | subjected the display to be used for skin improvement and / or treatment. In addition to the display on the package of food and drink, the display method includes publication in a pamphlet, advertisement, and the like.

本発明の組成物及び飲食品を医薬品として用いる場合には、錠剤、カプセル剤、顆粒剤、散剤、シロップ剤等の使用形態、使用方法を採用することができる。この場合、主剤の賦形剤、結合剤、崩壊剤、滑沢剤、矯味剤、矯臭剤、溶解補助剤、懸濁剤、コーティング剤等に、通常の補助剤を用いて常法に従い、製剤化することができる。  When using the composition and food / beverage products of this invention as a pharmaceutical, the usage form and usage method, such as a tablet, a capsule, a granule, a powder, a syrup, are employable. In this case, according to a conventional method using normal adjuvants, such as excipients, binders, disintegrating agents, lubricants, flavoring agents, flavoring agents, solubilizing agents, suspension agents, coating agents, etc. Can be

本発明の発酵乳は、皮膚改善用及び／又は治療用の発酵乳であって、ブルガリア菌（Lactobacillus delbrueckii subspecies bulgaricus）及びサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）を用いて調製したものである。  The fermented milk of the present invention is fermented milk for skin improvement and / or treatment, and is prepared using Bulgarian bacteria (Lactobacillus delbrueckii subspecies bulgaricus) and Thermofilus OLS3059 (Streptococcus thermophilus OLS3059).

かかる本発明の皮膚改善用及び／又は治療用の発酵乳は、発酵乳の調製に用いる、カードを形成する能を持った、製造特性の良い乳酸菌の中から選抜された皮膚改善効果及び／又は治療効果が高いサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）を用いて調整されているので、皮膚改善効果及び／又は治療効果が高い。すなわち、前記本発明の発酵乳は、皮膚改善効果及び／又は治療効果が高く、これらの用途に適している。  Such fermented milk for skin improvement and / or treatment of the present invention is a skin improvement effect selected from lactic acid bacteria having the ability to form a card and having good production characteristics, and / or used for preparing fermented milk. Since it is adjusted using Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) having a high therapeutic effect, the skin improvement effect and / or the therapeutic effect is high. That is, the fermented milk of the present invention has a high skin improvement effect and / or therapeutic effect and is suitable for these uses.

更に、前記のようなサーモフィルス菌 OLS3059を、ブルガリア菌と組み合わせて、乳酸菌を調整する、例えば、これらを組み合わせてスターターとして用いることで、比較的、短時間でカードを形成することができる。  Furthermore, the thermophilus OLS3059 as described above is combined with Bulgarian bacteria to adjust lactic acid bacteria. For example, these can be combined and used as a starter to form a card in a relatively short time.

前記本発明の皮膚改善用及び／又は治療用の発酵乳において、ブルガリア菌（Lactobacillus delbrueckii subspecies bulgaricus）には、例えば、明治乳業株式会社製のプレーンヨーグルト、ハードヨーグルト、ソフトヨーグルトから単離して得られる乳酸菌を用いることができる。これらブルガリア菌とサーモフィルス菌との組合せにより調製される本発明の発酵乳は、嗜好性に優れ、風味が良く、舌触りが滑らかであり、製品の輸送時にカードが崩れにくく、カードが丈夫であるといった特徴がある。  In the fermented milk for skin improvement and / or treatment of the present invention, Bulgarian bacteria (Lactobacillus delbrueckii subspecies bulgaricus) are obtained by isolation from, for example, plain yogurt, hard yogurt, and soft yogurt manufactured by Meiji Dairies Co., Ltd. Lactic acid bacteria can be used. The fermented milk of the present invention prepared by the combination of these Bulgarian bacteria and Thermophilus bacteria has excellent palatability, good taste, smooth touch, the card is not easily collapsed during product transportation, and the card is strong. There are features such as.

前述したブルガリア菌（Lactobacillus delbrueckii subspecies bulgaricus）及びサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）を用いて調製した本発明の皮膚改善用及び／又は治療用の発酵乳は、コラーゲンペプチド及び／又はセラミドを含有するものとすることができる。  The fermented milk for skin improvement and / or treatment of the present invention prepared using the aforementioned bacterium Bulgaria (Lactobacillus delbrueckii subspecies bulgaricus) and thermophilus OLS3059 (Streptococcus thermophilus OLS3059) contains a collagen peptide and / or ceramide. Can be.

実施例に後記する通り、コラーゲンペプチドやセラミドを含有する本発明の前述した発酵乳と、含有していない本発明の前述した発酵乳を比較したところ、コラーゲンペプチドやセラミドを含有する発酵乳において、皮膚改善効果及び／又は治療効果が高い傾向が得られた。すなわち、前述したようにブルガリア菌及びサーモフィルス菌 OLS3059を用いて調製しただけの本発明の発酵乳に比較し、コラーゲンペプチド及び／又はセラミドを混合して使用することで、皮膚改善効果及び／又は治療効果が高くなった。これは、皮膚改善効果及び／又は治療効果が高い乳酸菌（サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059））とコラーゲンペプチド及び／又はセラミドとを混合したことによる相乗効果と考えられる。  As will be described later in the Examples, when the fermented milk of the present invention containing collagen peptide or ceramide is compared with the fermented milk of the present invention not containing the collagen peptide or ceramide in fermented milk containing collagen peptide or ceramide, The tendency for the skin improvement effect and / or the treatment effect to be high was obtained. That is, as described above, compared to the fermented milk of the present invention only prepared using Bulgarian bacteria and Thermophilus OLS3059, by using a mixture of collagen peptide and / or ceramide, skin improvement effect and / or The therapeutic effect became high. This is considered to be a synergistic effect by mixing a lactic acid bacterium (Thermophyllus OLS3059 (Streptococcus thermophilus OLS3059)) with high skin improvement effect and / or therapeutic effect and collagen peptide and / or ceramide.

このような皮膚改善効果及び／又は治療効果の相乗効果という観点から、本発明の発酵乳には、コラーゲンペプチド及び／又はセラミドの他に、スフィンゴミエリン、イソフラボン、コンドロイチン、ヒアルロン酸等、飲食品、医薬品に用いる各種新陳代謝の改善効果を持つ有用成分を添加することも好ましい。  From the viewpoint of the synergistic effect of the skin improvement effect and / or the therapeutic effect, in addition to the collagen peptide and / or ceramide, the fermented milk of the present invention includes foods and drinks such as sphingomyelin, isoflavone, chondroitin, hyaluronic acid, It is also preferable to add useful components having an effect of improving various metabolisms used in pharmaceuticals.

以上の本発明の皮膚改善用及び／又は治療用の発酵乳について、皮膚改善効果及び／又は治療効果に影響する因子を見いだすため、ヒト試験により、さらに詳細な検討を進めたところ、以上の本発明の発酵乳は、発酵乳の代表的な作用とされる整腸改善効果の高かったヒトに対して皮膚改善効果及び／又は治療効果も高いとの知見を得た。  With regard to the fermented milk for skin improvement and / or treatment of the present invention described above, in order to find out the factors affecting the skin improvement effect and / or the therapeutic effect, further detailed studies were conducted by human tests. It was found that the fermented milk of the invention has a high skin improvement effect and / or therapeutic effect for humans who had a high effect of improving the intestinal regulation, which is a typical action of fermented milk.

具体的には、コラーゲンペプチドやセラミドを含有する本発明の前述した皮膚改善用及び／又は治療用の発酵乳と、含有していない本発明の前述した皮膚改善用及び／又は治療用の発酵乳とを用いて、整腸改善効果の程度と、皮膚改善効果の程度を比較することにより、前記した通りの知見を得た。  Specifically, the above-described fermented milk for skin improvement and / or treatment of the present invention containing collagen peptide or ceramide, and the above-described fermented milk for skin improvement and / or treatment of the present invention not containing The above findings were obtained by comparing the degree of the intestinal improvement effect and the degree of the skin improvement effect.

すなわち、本発明の前述した皮膚改善用及び／又は治療用の発酵乳は、整腸（便通）改善効果及び／又は治療効果の高かったヒトに対して、前記皮膚改善効果及び／又は治療効果が高いことを特徴としている。  That is, the above-described fermented milk for skin improvement and / or treatment of the present invention has the above skin improvement effect and / or treatment effect on a human who has a high effect of improving bowel regulation (feces) and / or treatment. It is characterized by high price.

以上の本発明の皮膚改善用及び／又は治療用の発酵乳を製造する本発明の発酵乳製造方法は、原料乳を調製した後、ブルガリア菌（Lactobacillus delbrueckii subspecies bulgaricus）及びサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）をスターターとして添加し、容器へ充填し、発酵させて、カードを形成させた後に冷蔵する、あるいは、原料乳を調製した後、ブルガリア菌（Lactobacillus delbrueckii subspecies
bulgaricus）及びサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）をスターターとして添加し、発酵させて、カードを形成させた後に、カードを破砕し、容器へ充填し、冷蔵する、原料乳を調製した後に、ブルガリア菌（Lactobacillus delbrueckii subspecies bulgaricus）及びサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）をスターターとして添加し、発酵させて、カードを形成させた後に、カードを破砕し、冷却し、容器へ充填し、冷蔵するものである。The fermented milk production method of the present invention for producing fermented milk for skin improvement and / or treatment of the present invention described above comprises the preparation of raw material milk, followed by Bulgarian bacteria (Lactobacillus delbrueckii subspecies bulgaricus) and Thermofilus OLS3059 (Streptococcus Thermophilus OLS3059) is added as a starter, filled into a container, fermented to form a curd and refrigerated, or after preparing raw milk, Bulgarian bacteria (Lactobacillus delbrueckii subspecies
bulgaricus) and Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) as a starter, fermented to form a curd, crushed curd, filled into a container, refrigerated, after preparing raw milk, Bulgaria A fungus (Lactobacillus delbrueckii subspecies bulgaricus) and Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) are added as a starter, fermented to form a curd, then the card is crushed, cooled, filled into a container, and refrigerated It is.

ここで、ブルガリア菌（Lactobacillus delbrueckii subspecies bulgaricus）及びサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）をスターターとして添加するまでに行う原料乳の調製は、従来一般の発酵乳製造工程と同じく、原料乳を調製し、均質化や殺菌・冷却などの処理を行って原料乳を調製するものである。  Here, the raw milk is prepared by adding Bulgarian bacteria (Lactobacillus delbrueckii subspecies bulgaricus) and Thermofilus OLS3059 (Streptococcus thermophilus OLS3059) as a starter. The raw material milk is prepared by performing processes such as homogenization, sterilization and cooling.

このように、前述した本発明の発酵乳を製造する本発明の製造方法においては、発酵乳の調製に用いる、カードを形成する能を持った、製造特性の良い乳酸菌の中から選抜された皮膚改善効果及び／又は治療効果が高いサーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）と、ブルガリア菌とを組み合わせて、スターターとしている。  Thus, in the production method of the present invention for producing the fermented milk of the present invention described above, the skin selected from lactic acid bacteria having the ability to form a card and having good production characteristics used for the preparation of fermented milk. Thermophilus OLS3059 (Streptococcus thermophilus OLS3059), which has a high improving effect and / or therapeutic effect, is combined with a Bulgarian bacterium to form a starter.

そのため、皮膚改善効果等を持つ従来までの乳酸菌での問題点（課題点）が解決されている。従来は、皮膚改善効果等を持つが、発酵乳の製造特性が悪い乳酸菌と、カードを形成するための製造特性が良い乳酸菌とを別に管理したり、発酵時間が長くなることで、製造時間の全体が長くなったりといった問題が起こっていた。つまり、皮膚改善効果等を持つ従来までの乳酸菌は、発酵乳の工業的な大量生産（商業的な生産）等には適していなかった。  Therefore, problems (problems) with conventional lactic acid bacteria having a skin improvement effect and the like have been solved. Conventionally, it has a skin improvement effect, etc., but lactic acid bacteria with poor production characteristics of fermented milk and lactic acid bacteria with good production characteristics for forming a card are managed separately, or the fermentation time is prolonged, There were problems such as the whole becoming longer. That is, the conventional lactic acid bacteria having skin improvement effects and the like are not suitable for industrial mass production (commercial production) of fermented milk.

しかし、本発明の発酵乳の製造方法は、前記した問題点を解決しているため、商業的な生産に適用できる。工程数が複雑でないことが商業的な生産には重要である。  However, the method for producing fermented milk of the present invention can be applied to commercial production because it solves the aforementioned problems. It is important for commercial production that the number of processes is not complex.

前述した本発明の発酵乳の製造方法で、原料乳を調製する工程における均質化は、殺菌前と殺菌後のいずれか、あるいは双方において行うことができる。  The homogenization in the step of preparing raw material milk in the method for producing fermented milk of the present invention described above can be performed either before or after sterilization, or both.

また、前述したように、発酵させてからの冷却は、カードを形成させた後、カードを破砕した後、容器へ充填した後の何れでも良い。  Further, as described above, the cooling after fermentation may be performed after the card is formed, after the card is crushed, and then filled into the container.

さらに、カードを破砕した後に、果肉、野菜、各種ソース、及び／又は各種添加剤を添加・混合することもできる。  Further, after the curd is crushed, pulp, vegetables, various sauces, and / or various additives can be added and mixed.

本発明の発酵乳の製造方法において発酵時間は、通常の発酵乳の製造に用いることができる程度である、8時間以内、好ましくは6あるいは5時間以内、より好ましくは4時間以内である。  In the method for producing fermented milk of the present invention, the fermentation time is within 8 hours, preferably within 6 or 5 hours, more preferably within 4 hours, which is a level that can be used for the production of ordinary fermented milk.

また、本発明の皮膚改善用及び／又は治療用の発酵乳は、風味が極めて優れているため、常用することができ、無理なく継続的に摂取ができる。これにより、皮膚改善効果や治療効果を、より高めることができる。  Moreover, since the fermented milk for skin improvement and / or treatment of the present invention has an extremely excellent flavor, it can be used regularly and can be taken continuously without difficulty. Thereby, a skin improvement effect and a therapeutic effect can be heightened more.

以下、本発明に関して好ましい実施例を挙げて説明するが、本発明は、これにより限定されるものではない。  Hereinafter, the present invention will be described with reference to preferred examples, but the present invention is not limited thereto.

（アトピー性皮膚炎抑制効果の in vivo 試験による検証）
マウス雌 NC/Ngaの4週齢（日本エスエルシー(株)製）を訓化飼育した後に、4群に分けた。すなわち、蒸留水投与群（n＝10）、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059））（以下、OLS3059とも称す。ブルガリアヨーグルトLB81（（登録商標）明治乳業株式会社製）より単離した。）投与群（n＝10）、皮膚炎非惹起群（n＝7）及び、OLS3059投与群との比較対照に、Lactobacillus rhamnosus ATCC 53103（以下、ATCC 53103とも称す。）投与群（n＝10）に群分けし、飼料（商品名：CRF-1、オリエンタル酵母工業(株)製）及び蒸留水を自由摂取させた。ここで、ATCC 53103はアトピー性皮膚炎に効果があることが知られている乳酸菌である。(Verification of atopic dermatitis inhibitory effect by in vivo test)
Mouse female NC / Nga 4 weeks old (manufactured by Nippon SLC Co., Ltd.) were bred and reared, and then divided into 4 groups. Namely, distilled water administration group (n = 10), thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (hereinafter also referred to as OLS3059, isolated from Bulgaria yogurt LB81 (registered trademark) manufactured by Meiji Dairies). The group (n = 10), the non-dermatitis induced group (n = 7) and the OLS3059 administration group were compared with the Lactobacillus rhamnosus ATCC 53103 (hereinafter also referred to as ATCC 53103) administration group (n = 10). Separately, feed (trade name: CRF-1, manufactured by Oriental Yeast Co., Ltd.) and distilled water were ingested freely. Here, ATCC 53103 is a lactic acid bacterium known to have an effect on atopic dermatitis.

皮膚炎非惹起群を除いた3群は試験期間中、蒸留水あるいは各種乳酸菌をゾンデにより経口投与した。そして、後記する方法に従い、皮膚炎の惹起を試験開始の7日後（day 0）から連日で行った。すなわち、蒸留水投与群は試験期間（1日目（day -7）〜21日後（day
14））に亘り、連日で蒸留水を胃内に経口投与（1 mg／日／マウス）し、各種乳酸菌の投与群も同様にして、連日で乳酸菌の水懸濁液を胃内に経口投与（1 mg／日／マウス）した。各種乳酸菌の懸濁液は、加熱処理（温度 75℃、60分間）した菌体の凍結乾燥物を蒸留水に懸濁して作成した。各種乳酸菌の懸濁液について菌体濃度は、ATCC 53103が7.13×１０８（10の8乗）cfu／g、OLS3059が8.56×１０７（10の7乗）cfu／gであった。Three groups excluding the non-induced dermatitis group were orally administered with distilled water or various lactic acid bacteria during the test period. Then, according to the method described later, dermatitis was induced every day from 7 days after the start of the test (day 0). That is, the group administered with distilled water has a test period (day -7) to 21 days later (day
14)), distilled water was orally administered into the stomach every day (1 mg / day / mouse), and various lactic acid bacteria administration groups were orally administered daily into the stomach. (1 mg / day / mouse). Suspensions of various lactic acid bacteria were prepared by suspending lyophilized cells of heat-treated cells (temperature 75 ° C., 60 minutes) in distilled water. Regarding the suspensions of various lactic acid bacteria, the cell concentrations of ATCC 53103 were 7.13 × 10 8 (10 8) cfu / g, and OLS3059 was 8.56 × 10 7 (10 7) cfu / g.

試験開始の7日後（day 0）より皮膚炎を惹起し、発症推移をスコア化した。また、皮膚炎惹起開始の15日後（day 15）に血清を採取し、IgE濃度をELISA法により測定した。IgE濃度はPharmingen社製の抗体を用いてPharmingen社が推奨するプロトコールの一部を改変して測定した。  Dermatitis was induced 7 days after the start of the test (day 0), and the onset transition was scored. Serum was collected 15 days after the onset of dermatitis initiation (day 15), and the IgE concentration was measured by ELISA. The IgE concentration was measured by modifying a part of the protocol recommended by Pharmingen using an antibody manufactured by Pharmingen.

ダニ破砕物液の調製は以下の方法で行った。すなわち、ヤケヒョウヒダニの全虫体（Mite-Dp、エル・エス・エル社製）を無水エーテルで脱脂した後に、蒸留水を添加して超音波破砕処理した。ついで、水溶性画分を遠心分離処理し、凍結乾燥した後に、タンパク質濃度で4.5 mg／ml（BSA 換算、BioRAD 社のDC protein assay で測定した。）に蒸留水で調製した。  The tick crushed liquid was prepared by the following method. That is, the whole body of a mushroom leopard mite (Mite-Dp, manufactured by LSL) was degreased with anhydrous ether, and then distilled water was added for ultrasonic crushing treatment. Subsequently, the water-soluble fraction was centrifuged, freeze-dried, and then prepared with distilled water at a protein concentration of 4.5 mg / ml (measured by BSA conversion, BioRAD DC protein assay).

皮膚炎惹起試験は海野らの方法（海野哲史 他、アレルギー 50：1152-1162、2001）を改変して行った。皮膚炎惹起部位（頭部、耳介部及び頸部）の毛をバリカンで刈った後に、SDS水溶液（4％）を全マウスの皮膚炎惹起部位に、刷毛で20 回、塗布した。塗布量は20回で約60μlに相当する。SDS 水溶液が乾燥した後に、皮膚炎惹起群には、ダニ破砕物液を、皮膚炎非惹起群には、蒸留水を同様にして各々20回、塗布した。前記した操作を1日に1セットで毎日繰り返すことにより、皮膚炎を惹起させ、試験開始の7日後（day 0）から試験終了日まで連日で繰り返した。  The dermatitis induction test was performed by modifying the method of Unno et al. (Tetsufumi Unno et al., Allergy 50: 1152-1162, 2001). After shaving the hair at the site of dermatitis (head, auricle and neck) with a clipper, an aqueous SDS solution (4%) was applied to the dermatitis site of all mice 20 times with a brush. The amount applied is 20 times, which corresponds to about 60 μl. After the SDS aqueous solution was dried, tick crushed liquid was applied to the dermatitis-induced group and distilled water was applied to the non-dermatitis-induced group 20 times in the same manner. Dermatitis was caused by repeating the above-mentioned operation every day in one set per day, and repeated every day from 7 days after the start of the test (day 0) to the end of the test.

IgEの測定は以下の方法で行った。すなわち、96 ウェルプレートに１次抗体用の抗IgE抗体（Pharmingen社製）を2μg／ml で添加し、温度 37℃で1時間、静置した。Tween 20／PBS（PBS−Tween、0.05％）で洗浄した後に、BSA／PBS（1％） を添加し、室温で30分間、静置した。PBS−Tweenで洗浄した後に、血清試料及び標準曲線作成用のIgE（Pharmingen社製）を添加し、室温で30分間、静置した。PBS−Tweenで洗浄した後に、２次抗体用のビオチン−抗IgE 抗体（Pharmingen社製）を0.5μg/mlで添加し、室温で1時間、静置した。PBS−Tweenで洗浄した後に、ストレプトアビジン−HRP（Pharmingen社製）を添加し、室温で30分間、静置した。PBS−Tweenで洗浄した後に、TMB＋Substrate Chromogen（DAKO社製）を添加し、発色反応を開始した。発色反応の後に、硫酸（1N）を添加し、吸光度（450 nm）をマイクロプレートリーダーで測定し、血清中のIgE濃度を算出した。  IgE was measured by the following method. That is, an anti-IgE antibody for primary antibody (Pharmingen) was added to a 96-well plate at 2 μg / ml and allowed to stand at a temperature of 37 ° C. for 1 hour. After washing with Tween 20 / PBS (PBS-Tween, 0.05%), BSA / PBS (1%) was added and allowed to stand at room temperature for 30 minutes. After washing with PBS-Tween, a serum sample and IgE (Pharmingen) for preparing a standard curve were added, and allowed to stand at room temperature for 30 minutes. After washing with PBS-Tween, biotin-anti-IgE antibody for secondary antibody (manufactured by Pharmingen) was added at 0.5 μg / ml and allowed to stand at room temperature for 1 hour. After washing with PBS-Tween, streptavidin-HRP (Pharmingen) was added and allowed to stand at room temperature for 30 minutes. After washing with PBS-Tween, TMB + Substrate Chromogen (DAKO) was added to start the color reaction. After the color reaction, sulfuric acid (1N) was added, and the absorbance (450 nm) was measured with a microplate reader to calculate the IgE concentration in the serum.

皮膚炎発症スコアの推移を図１に示した。スコア化は、[1] 乾皮・痂皮形成、[2] 発赤・出血、[3] 組織脱落・擦り傷、[4] 浮腫、[5] 掻痒行動の5 項目について、「０．無症状」、「１．軽度」、「２．中程度」、「３．重度」の4段階で行い、各マウスにおける各スコアの合計を算出し、評価した。皮膚炎惹起開始の13日後（day 13）の発症スコアについて、OLS3059投与群は蒸留水投与群と比較して有意に低かった。一方、ATCC 53103投与群は蒸留水投与群と比較して大差がなかった。  The transition of the dermatitis onset score is shown in FIG. Scoring was done for five items: [1] dry skin / scab formation, [2] redness / bleeding, [3] tissue loss / abrasion, [4] edema, [5] pruritus behavior, “0. Asymptomatic”. , “1. Mild”, “2. Moderate”, and “3. Severe”. The total score of each mouse was calculated and evaluated. Regarding the onset score 13 days after the onset of dermatitis initiation (day 13), the OLS3059 administration group was significantly lower than the distilled water administration group. On the other hand, the ATCC 53103 administration group was not significantly different from the distilled water administration group.

総IgE濃度を図２に示した。皮膚炎惹起開始の15日後（day 15）の血清中の総IgEについて、OLS3059投与群は蒸留水投与群と比較してIgE濃度が有意に低かった。一方、ATCC 53103投与群は蒸留水投与群と比較してIgE濃度が幾らか低かったが、有意差は認められなかった。ATCC 53103はアトピー性皮膚炎に効果があることが知られている乳酸菌であるが、OLS3059は、そのATCC 53103よりもアトピー性皮膚炎の発症に対して抑制効果が高かった。  The total IgE concentration is shown in FIG. Regarding total IgE in serum 15 days after the onset of dermatitis initiation (day 15), the OLS3059 administration group had significantly lower IgE concentration than the distilled water administration group. On the other hand, the IgE concentration in the ATCC 53103 administration group was somewhat lower than that in the distilled water administration group, but no significant difference was observed. ATCC 53103 is a lactic acid bacterium known to have an effect on atopic dermatitis, but OLS3059 has a higher inhibitory effect on the development of atopic dermatitis than ATCC 53103.

（アトピー性皮膚炎抑制効果の in vivo 試験による検証）
マウス雌 NC/Ngaの4週齢（日本エスエルシー(株)製）を訓化飼育した後に３群に分けた。すなわち、蒸留水投与群（n＝4）、ブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1、以下、OLL1073R-1とも称す。）投与群（n＝6）、及びサーモフィルス菌OLS3059（Streptococcus thermophilus OLS3059。ブルガリアヨーグルトLB81（明治乳業(株)製）より単離した。）投与群（n＝5）に群分けし、飼料（商品名：CRF-1、オリエンタル酵母工業(株)製）及び蒸留水を自由摂取させた。皮膚炎の惹起期間を３０日間とした他は、実施例１と同様の実験条件とした。(Verification of atopic dermatitis inhibitory effect by in vivo test)
Mouse female NC / Nga 4 weeks old (manufactured by Japan SLC Co., Ltd.) was bred and reared and divided into 3 groups. That is, a distilled water administration group (n = 4), a Bulgarian bacterium OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1, hereinafter also referred to as OLL1073R-1) administration group (n = 6), and a thermophilus OLS3059 (Streptococcus thermophilus OLS3059, isolated from Bulgarian yogurt LB81 (manufactured by Meiji Dairies Co., Ltd.) divided into administration groups (n = 5), feed (trade name: CRF-1, Oriental Yeast Co., Ltd.) and Distilled water was given ad libitum. The experimental conditions were the same as in Example 1, except that the period of induction of dermatitis was 30 days.

皮膚炎発症スコアの推移を図３に示した。皮膚炎惹起開始の１３日後（day 13）の発症スコアについて、OLL1073R-1投与群とOLS3059投与群は蒸留水投与群と比較して有意に低かった。  The transition of the dermatitis onset score is shown in FIG. Regarding the onset score 13 days after the onset of dermatitis initiation (day 13), the OLL1073R-1 administration group and the OLS3059 administration group were significantly lower than the distilled water administration group.

総IgE濃度を図４に示した。血清中の総IgEについて、OLL1073R-1投与群とOLS3059投与群は蒸留水投与群と比較してIgE濃度が有意に低かった。本発明のOLS3059はアトピー性皮膚炎の発症に対して抑制効果があることが認められた。また、OLL1073R-1についてもアトピー性皮膚炎の発症に対して抑制効果があることが認められたが、IgE濃度は本発明のOLS3059の方が低かった。  The total IgE concentration is shown in FIG. Regarding serum total IgE, the OLL1073R-1 administration group and the OLS3059 administration group had significantly lower IgE concentrations than the distilled water administration group. The OLS3059 of the present invention was found to have an inhibitory effect on the development of atopic dermatitis. OLL1073R-1 was also found to have an inhibitory effect on the onset of atopic dermatitis, but the IgE concentration was lower in OLS3059 of the present invention.

（アトピー性皮膚炎抑制効果の in vivo 試験による検証）
アトピー性皮膚炎の発症に対して本発明のOLS3059と遜色のない抑制効果を発揮することが実施例２で確認されたOLL1073R-1と、本発明のOLS3059とを組み合わせて使用した場合におけるアトピー性皮膚炎の発症に対する抑制効果を検討した。(Verification of atopic dermatitis inhibitory effect by in vivo test)
Atopic properties in the case of using OLL1073R-1 confirmed in Example 2 and OLS3059 of the present invention in combination with OLS3059 of the present invention to exhibit the same inhibitory effect as OLS3059 of the present invention against the onset of atopic dermatitis The inhibitory effect on the onset of dermatitis was examined.

本発明のOLS3059とOLL1073R-1との組み合わせと比較する対象として、両方ともブルガリアヨーグルト（明治乳業(株)製）から単離されるLactobacillus delbrueckii subspecies bulgaricus MEP1705601とStreptococcus thermophilus MEP1705601との組み合わせを採用した。  As a target to be compared with the combination of OLS3059 and OLL1073R-1 of the present invention, a combination of Lactobacillus delbrueckii subspecies bulgaricus MEP1705601 and Streptococcus thermophilus MEP1705601 both isolated from Bulgarian yogurt (manufactured by Meiji Dairies) was employed.

マウス雌 NC/Ngaの4週齢（日本エスエルシー(株)製）を訓化飼育した後に4群に分けた。Mouse female NC / Nga 4 weeks old (manufactured by Nippon SLC Co., Ltd.) were bred and reared, and then divided into 4 groups.

すなわち、Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1とStreptococcus thermophilus OLS3059で調製した発酵物の投与群（以下、OLL1073R-1 + OLS3059投与群とも称す。）（n＝8）、Lactobacillus delbrueckii subspecies bulgaricus MEP1705601とStreptococcus thermophilus MEP1705601で調製した発酵物の投与群（以下、LB MEP1705601 + ST MEP1705601投与群とも称す。）（n＝9）、未発酵物の投与群（n＝9）及び皮膚炎非惹起かつ未発酵物の投与群（以下、非惹起群とも称す。）（n＝4）に群分けした。発酵物、未発酵物の摂取量は、いずれも100 mg／mouse／dayとし、試験終了日まで連日で経口投与した。  That is, Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1 and Streptococcus thermophilus OLS3059 fermented product administration group (hereinafter also referred to as OLL1073R-1 + OLS3059 administration group) (n = 8), Lactobacillus delbrueckii subspecies bulgaricus MEP1705601phil Administration group of fermented product prepared in (hereinafter also referred to as LB MEP1705601 + ST MEP1705601 administration group) (n = 9), administration group of unfermented product (n = 9), administration of non-fermented and non-fermented product The groups were divided into groups (hereinafter also referred to as non-induced groups) (n = 4). The intake of fermented material and unfermented material was 100 mg / mouse / day, and were orally administered every day until the end of the test.

発酵物の菌数は、OLL1073R-1で1×109 cfu／g、OLS3059で3×109 cfu／g、LB MEP1705601で8.6×108 cfu／g、ST MEP1705601で2.1×109 cfu／gである。The number of bacteria in the fermented product is 1 × 10 9 cfu / g for OLL1073R-1, 3 × 10 9 cfu / g for OLS3059, 8.6 × 10 8 cfu / g for LB MEP1705601, 2.1 × 10 9 cfu / g for ST MEP1705601 It is.

発酵物と未発酵物は凍結乾燥した後に、投与する時に蒸留水で懸濁して調製した。皮膚炎の惹起期間を２９日間とした他は、実施例１と同様の実験条件とした。 The fermented product and the unfermented product were prepared by lyophilizing and then suspending in distilled water at the time of administration. The experimental conditions were the same as in Example 1, except that the period of induction of dermatitis was 29 days.

皮膚炎発症スコアの推移を図５に示した。皮膚炎惹起開始の１４日後（day 14）の発症スコアについて、OLL1073R-1 + OLS3059投与群は、LB MEP1705601 + ST MEP1705601投与群や未発酵物の投与群と比較して低かった。  The transition of the dermatitis onset score is shown in FIG. Regarding the onset score 14 days after the onset of dermatitis initiation (day 14), the OLL1073R-1 + OLS3059 administration group was lower than the LB MEP1705601 + ST MEP1705601 administration group and the unfermented product administration group.

また、皮膚炎惹起開始の１４日後（day 14）以降では、OLL1073R-1 + OLS3059投与群はLB MEP1705601 + ST MEP1705601投与群や未発酵物の投与群と比較して有意に低かった。  Further, after 14 days (day 14) after the onset of dermatitis induction, the OLL1073R-1 + OLS3059 administration group was significantly lower than the LB MEP1705601 + ST MEP1705601 administration group and the unfermented product administration group.

アトピー性皮膚炎の発症に対して本発明のOLS3059と遜色のない抑制効果を発揮することが実施例２で確認されたOLL1073R-1と、本発明のOLS3059とを組み合わせて使用するとアトピー性皮膚炎の発症に対して抑制効果があることが認められた。  When OLL1073R-1 confirmed in Example 2 and OLS3059 of the present invention are used in combination with OLS3059 of the present invention to exhibit the same inhibitory effect as OLS3059 of the present invention against the onset of atopic dermatitis, atopic dermatitis It was confirmed that there was an inhibitory effect on the onset of the disease.

（発酵乳の製造例１）
生乳 50.0 kg、脱脂粉乳 5.0 kg、砂糖 8.0 kg、コラーゲンペプチド（商品名：ニッピペプタイド、ニッピコラーゲン化粧品社製） 1.0 kg、セラミド含有こんにゃく芋エキス 0.1 kg（商品名：こんにゃくセラミド、ユニチカ(株)製）、香料 0.1 kg、水 33.8 kgを温度 65℃で混合溶解し、調合乳を作成した。この調合乳を温度 65℃で均質化処理（圧力
100 kg／cm2）した後に、温度 95℃で2分間、殺菌処理し、直ちに温度 43〜45℃に冷却した。この殺菌した調合乳に、乳酸菌スターター 2.0 kgを添加し、容器に充填した後に、温度 43℃で4時間、発酵させ、発酵乳（セットタイプのヨーグルト）を得た。ここで、乳酸菌スターターには、ブルガリア菌（Lactobacillus bulgaricus 2038、ブルガリアヨーグルトLB81（（登録商標）明治乳業(株)製）より単離した。）と、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059））（以下、OLS3059とも称す。ブルガリアヨーグルトLB81（（登録商標）明治乳業株式会社製）より単離した。）の等量培養液を用いた。(Production Example 1 of Fermented Milk)
Raw milk 50.0 kg, skim milk powder 5.0 kg, sugar 8.0 kg, collagen peptide (trade name: Nippi Peptide, manufactured by Nippi Collagen Cosmetics Co., Ltd.) 1.0 kg, ceramide-containing konjac extract 0.1 kg (trade name: Konjac ceramide, manufactured by Unitika Ltd.) ), 0.1 kg of fragrance and 33.8 kg of water were mixed and dissolved at a temperature of 65 ° C to prepare a formula. This formula is homogenized at a temperature of 65 ° C (pressure
100 kg / cm 2 ), sterilized at a temperature of 95 ° C. for 2 minutes, and immediately cooled to a temperature of 43 to 45 ° C. To this sterilized formula milk, 2.0 kg of lactic acid bacteria starter was added, filled into a container, and then fermented at a temperature of 43 ° C. for 4 hours to obtain fermented milk (set type yogurt). Here, lactic acid bacteria starters include Bulgarian bacteria (Lactobacillus bulgaricus 2038, Bulgarian yogurt LB81 (manufactured by Meiji Dairies Co., Ltd.)) and Thermophilus OLS3059 (Streptococcus thermophilus OLS3059)) , Also referred to as OLS3059, an equivalent culture solution of Bulgarian yogurt LB81 (isolated from (registered trademark) Meiji Dairies Co., Ltd.) was used.

（発酵乳飲料の製造例１）
生乳 23.0 kg、脱脂粉乳 12.1 kg、水 62.9 kgを温度 70℃で混合溶解し、調合乳を作成した。この調合乳を温度 65℃で均質化処理（圧力 150 kg／cm2）した後に、温度 95℃で10分間、殺菌処理し、直ちに温度 40〜45℃に冷却した。この殺菌した調合乳に、乳酸菌スターター 2.0 kgを添加し、温度 40〜45℃で5時間、発酵させ、発酵乳を得た。(Production Example 1 of Fermented Milk Beverage)
Mixed milk was prepared by mixing and dissolving 23.0 kg of raw milk, 12.1 kg of skim milk powder, and 62.9 kg of water at a temperature of 70 ° C. The formula was homogenized at a temperature of 65 ° C. (pressure 150 kg / cm 2 ), sterilized at a temperature of 95 ° C. for 10 minutes, and immediately cooled to a temperature of 40 to 45 ° C. To this sterilized formula, 2.0 kg of lactic acid bacteria starter was added and fermented at a temperature of 40 to 45 ° C. for 5 hours to obtain fermented milk.

ここで、乳酸菌スターターには、ブルガリア菌（Lactobacillus bulgaricus 2038、ブルガリアヨーグルトLB81（（登録商標）明治乳業(株)製）より単離した。）と、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059））（以下、OLS3059とも称す。ブルガリアヨーグルトLB81（（登録商標）明治乳業株式会社製）より単離した。）の等量培養液を用いた。  Here, lactic acid bacteria starters include Bulgarian bacteria (Lactobacillus bulgaricus 2038, Bulgarian yogurt LB81 (manufactured by Meiji Dairies Co., Ltd.)) and Thermophilus OLS3059 (Streptococcus thermophilus OLS3059)) , Also referred to as OLS3059, an equivalent culture solution of Bulgarian yogurt LB81 (isolated from (registered trademark) Meiji Dairies Co., Ltd.) was used.

この発酵乳のカードを機械的に破壊するため、均質化処理（圧力 150 kg／cm2）した後に、温度 5℃に冷却し、調合発酵乳を得た。一方、ペクチン 3.0 kg、砂糖 2.0 kg、甘味料 0.02 kg、香料 0.1 kg、水 34.0 kgを温度 65℃で混合溶解し、温度 130℃で2秒間、殺菌処理した後に、直ちに温度 5℃に冷却し、糖液を作成した。In order to mechanically break the curd of this fermented milk, it was homogenized (pressure 150 kg / cm 2 ) and then cooled to a temperature of 5 ° C. to obtain a fermented fermented milk. Meanwhile, 3.0 kg of pectin, 2.0 kg of sugar, 0.02 kg of sweetener, 0.1 kg of fragrance, and 34.0 kg of water are mixed and dissolved at a temperature of 65 ° C, sterilized at a temperature of 130 ° C for 2 seconds, and then immediately cooled to a temperature of 5 ° C. A sugar solution was created.

調合発酵乳と糖液を所定の濃度で混合して、発酵乳飲料（ドリンクタイプのヨーグルト）を得た。  The blended fermented milk and sugar solution were mixed at a predetermined concentration to obtain a fermented milk beverage (drink type yogurt).

（発酵乳飲料の製造例２）
生乳 23.0 kg、脱脂粉乳 12.1 kg、水 62.9 kgを温度 70℃で混合溶解し、調合乳を作成した。この調合乳を温度 65℃で均質化処理（圧力 150 kg／cm2）した後に、温度 95℃で10分間、殺菌処理し、直ちに温度 40〜45℃に冷却した。この殺菌した調合乳に、乳酸菌スターター 2.0 kgを添加し、温度 40〜45℃で5時間、発酵させ、発酵乳を得た。(Production Example 2 of Fermented Milk Beverage)
Mixed milk was prepared by mixing and dissolving 23.0 kg of raw milk, 12.1 kg of skim milk powder, and 62.9 kg of water at a temperature of 70 ° C. The formula was homogenized at a temperature of 65 ° C. (pressure 150 kg / cm 2 ), sterilized at a temperature of 95 ° C. for 10 minutes, and immediately cooled to a temperature of 40 to 45 ° C. To this sterilized formula, 2.0 kg of lactic acid bacteria starter was added and fermented at a temperature of 40 to 45 ° C. for 5 hours to obtain fermented milk.

ここで、乳酸菌スターターには、ブルガリア菌（Lactobacillus bulgaricus 2038、ブルガリアヨーグルトLB81（（登録商標）明治乳業(株)製）より単離した。）と、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059））（以下、OLS3059とも称す。ブルガリアヨーグルトLB81（（登録商標）明治乳業株式会社製）より単離した。）の等量培養液を用いた。  Here, lactic acid bacteria starters include Bulgarian bacteria (Lactobacillus bulgaricus 2038, Bulgarian yogurt LB81 (manufactured by Meiji Dairies Co., Ltd.)) and Thermophilus OLS3059 (Streptococcus thermophilus OLS3059)) , Also referred to as OLS3059, an equivalent culture solution of Bulgarian yogurt LB81 (isolated from (registered trademark) Meiji Dairies Co., Ltd.) was used.

この発酵乳のカードを機械的に破壊するため、均質化処理（圧力 150 kg／cm2）した後に、温度 5℃に冷却し、調合発酵乳を得た。一方、ペクチン 3.0 kg、砂糖 2.0 kg、甘味料 0.02 kg、コラーゲンペプチド（商品名：コラーゲンペプチド5200、新田ゼラチン社製） 1.0 kg、セラミド含有コーンエキス（商品名：コーンセラミドME1-R、辻製油(株)製）
0.03 kg、香料 0.1 kg、水 34.0 kgを温度 65℃で混合溶解し、温度 130℃で2秒間、殺菌処理した後に、直ちに温度 5℃に冷却し、糖液を作成した。In order to mechanically break the curd of this fermented milk, it was homogenized (pressure 150 kg / cm 2 ) and then cooled to a temperature of 5 ° C. to obtain a fermented fermented milk. On the other hand, pectin 3.0 kg, sugar 2.0 kg, sweetener 0.02 kg, collagen peptide (trade name: collagen peptide 5200, manufactured by Nitta Gelatin Co., Ltd.) 1.0 kg, ceramide-containing corn extract (trade name: corn ceramide ME1-R, coconut oil (Made by Co., Ltd.)
0.03 kg, fragrance 0.1 kg, and water 34.0 kg were mixed and dissolved at a temperature of 65 ° C., sterilized at a temperature of 130 ° C. for 2 seconds, and then immediately cooled to a temperature of 5 ° C. to prepare a sugar solution.

調合発酵乳と糖液を所定の濃度で混合して、発酵乳飲料（ドリンクタイプのヨーグルト）を得た。  The blended fermented milk and sugar solution were mixed at a predetermined concentration to obtain a fermented milk beverage (drink type yogurt).

（乳飲料の製造例）
生乳 1000 mLに、サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059））（以下、OLS3059とも称す。ブルガリアヨーグルトLB81（（登録商標）明治乳業株式会社製）より単離した。）の凍結乾燥粉末 1 gを添加し、調合乳を作成した。この調合乳を均質化処理した後に、温度 130℃で3秒間、殺菌処理し、直ちに温度 10℃以下に冷却した。この殺菌した調合乳を容器に充填し、乳飲料を得た。(Example of milk beverage production)
Add 1 g of freeze-dried powder of Thermofilus OLS3059 (Streptococcus thermophilus OLS3059) (hereinafter also referred to as OLS3059, isolated from Bulgarian yogurt LB81 (registered trademark) Meiji Dairies) to 1000 mL of raw milk And formula was made. This homogenized milk was homogenized, sterilized at a temperature of 130 ° C. for 3 seconds, and immediately cooled to a temperature of 10 ° C. or lower. The sterilized formula was filled in a container to obtain a milk beverage.

（皮膚（肌）改善効果のヒト試験による検証）
前記した実施例４の発酵乳（Streptococcus thermophilus OLS3059、菌体濃度 85×１０７（10の7乗）cfu／g、コラーゲンペプチド1000 mg／90 g、セラミド300 μg／90 g）を試験食とし、摂取量 90 g／回、摂取頻度 2回／日（朝と夜の1回ずつ）として28日間でヒト試験を行った。女性31名（平均年齢31.8歳）を被験者とした。(Verification by skin test of skin (skin) improvement effect)
The fermented milk of Example 4 described above (Streptococcus thermophilus OLS3059, bacterial cell concentration 85 × 10 7 (10 to the 7th power) cfu / g, collagen peptide 1000 mg / 90 g, ceramide 300 μg / 90 g) was used as a test food, The human test was conducted for 28 days with an intake of 90 g / dose and an intake frequency of 2 times / day (once in the morning and at night). The subjects were 31 women (average age 31.8 years).

開始日（試験食摂取前）と終了日（28日目）に、被験者の皮膚（肌）の弾力性とキメ密度の評価・観察を行い、加えて医師による皮疹の観察を行った。なお、肌の弾力性は頬の左右から一方を選択し、1箇所を2回、測定した（商品名：CUTOMETER SEM575、Courage+Khazaka製）。肌のキメ密度は肌荒れ部位を選択し、1箇所を測定した（商品名：Visual Imager VI-20 株式会社インフォワード製）。総皮疹数は皮疹を数えて評価した。  On the start date (before the test meal intake) and the end date (28th day), the elasticity and texture density of the subject's skin (skin) were evaluated and observed, and in addition, a doctor observed the rash. In addition, the elasticity of the skin was selected twice from the left and right sides of the cheek, and one place was measured twice (trade name: CUTOMETER SEM575, made by Courage + Khazaka). For the skin texture density, a rough skin area was selected and one spot was measured (trade name: Visual Imager VI-20, manufactured by Inforward Co., Ltd.). The total number of eruptions was evaluated by counting eruptions.

開始日（試験食摂取前）と終了日（28日目）に、被験者本人へのアンケート調査を実施した。アンケートの内容を表１に示した。表１に示した通り、[1] つや、[2] はり、[3] くすみ、[4] しみ、[5] たるみ、[6] 毛穴、[7] キメ、[8] しわ（額）、[9] しわ（口元）、[10] しわ（目元）、[11] 乾燥具合、[12] べたつき、[13] 透明感、[14] 赤み、[15] ファンデーションのノリ、[16] むくみ、[17] 便秘、[18] くまの18項目について、5段階で評価した。そして、終了日に、被験者本人と医師が試験食の有用性を評価した。
A questionnaire survey was conducted on the subject on the start date (before taking the test meal) and the end date (day 28). The contents of the questionnaire are shown in Table 1. As shown in Table 1, [1] gloss, [2] beam, [3] dullness, [4] blotch, [5] sagging, [6] pores, [7] texture, [8] wrinkle (forehead), [9] Wrinkle (mouth), [10] Wrinkle (eye), [11] Dryness, [12] Stickiness, [13] Transparency, [14] Redness, [15] Nori of foundation, [16] Swelling, [17] Constipation, [18] The 18 items of the bear were rated on a five-point scale. On the end date, the subject and the doctor evaluated the usefulness of the test meal.

実施例５の試験食を摂取した際の皮膚（肌）の弾力性を評価した結果を図６に示した。実施例５の試験食を摂取することにより、肌の弾力性は有意に増加し、肌のはりが改善された。実施例５の試験食を摂取した際の肌のキメ密度を評価した結果を図７に示した。実施例５の試験食を摂取することにより、肌のキメ密度は有意に増加し、肌のキメが改善された。実施例５の試験食を摂取した際の総皮疹数を評価した結果を図８に示した。実施例５の試験食を摂取することにより、総皮疹数は有意に減少し、肌荒れが改善された。  The result of evaluating the elasticity of the skin (skin) when the test meal of Example 5 was ingested is shown in FIG. By ingesting the test meal of Example 5, the elasticity of the skin was significantly increased and the skin elasticity was improved. The result of evaluating the texture density of the skin when the test meal of Example 5 was ingested is shown in FIG. By ingesting the test meal of Example 5, the texture density of the skin was significantly increased and the texture of the skin was improved. The results of evaluating the total number of eruptions when the test meal of Example 5 was ingested are shown in FIG. By ingesting the test meal of Example 5, the total number of eruptions was significantly reduced and rough skin was improved.

被験者本人へのアンケート調査の結果を表２に示した。試験食を摂取することにより、被験者の肌状態、便秘が改善されることが確認された。被験者本人と医師が試験食の有用性を評価した結果を図９に示した。試験食を摂取することが肌に有用であることが被験者本人あるいは医師により認められた。サーモフィルス菌OLS3059（Streptococcus thermophilus OLS3059）ののすぐれた皮膚改善効果及び／又は治療効果が実証され、サーモフィルス菌OLS3059（Streptococcus thermophilus OLS3059）が、皮膚改善効果及び／又は治療効果を発揮させる用途に適していることが確認された。
Table 2 shows the results of the questionnaire survey for the subject. It was confirmed that the test subject's skin condition and constipation were improved by ingesting the test meal. FIG. 9 shows the results of evaluating the usefulness of the test meal by the subject himself and the doctor. The subject himself or doctor confirmed that taking the test meal was useful for the skin. Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) has been demonstrated to have excellent skin improvement and / or therapeutic effects, and Thermofilus OLS3059 (Streptococcus thermophilus OLS3059) is suitable for applications that exert skin improvement and / or therapeutic effects It was confirmed that

（整腸改善効果と皮膚改善効果との関係のヒト試験による検証）
前記した実施例５の発酵乳（Streptococcus thermophilus OLS3059、菌体濃度 50×１０７（10の7乗）cfu／g）及び実施例６の発酵乳（Streptococcus thermophilus OLS3059、菌体濃度 50×１０７（10の7乗）cfu／g、コラーゲンペプチド1000 mg／120 ml、セラミド300 μg／120 ml）を試験食とし、摂取量 120 ml／回、摂取頻度 2回／日（朝と夜の1回ずつ）として28日間でヒト試験を行った。実施例５の発酵乳飲料では、女性28名（平均年齢31.1歳）を、実施例６の発酵乳飲料では、女性28名（平均年齢30.3歳）を被験者とした。(Verification by human test of the relationship between intestinal improvement effect and skin improvement effect)
Fermented milk of Example 5 (Streptococcus thermophilus OLS3059, bacterial cell concentration 50 × 10 7 (10 7) cfu / g) and fermented milk of Example 6 (Streptococcus thermophilus OLS3059, bacterial cell concentration 50 × 10 7 ( 10 7) cfu / g, collagen peptide 1000 mg / 120 ml, ceramide 300 μg / 120 ml) as a test meal, intake 120 ml / dose, intake frequency 2 times / day (once in the morning and at night) ) As a human test in 28 days. In the fermented milk drink of Example 5, 28 women (average age 31.1 years) were used as subjects, and in the fermented milk drink of Example 6, 28 women (average age 30.3 years) were used as subjects.

実施例８と同様にして、被験者本人へのアンケート調査を実施した。アンケートの内容は表１に示した通りである。被験者本人へのアンケート調査の結果を表３及び表４に示した。試験食を摂取することにより、被験者の肌状態、便秘が改善されることが確認された。表１の[1] つや、[2] はり、[7] キメ、[11] 乾燥具合、[15] ファンデーションのノリ、[17] 便秘の6項目について、実施例６の試験食（コラーゲンペプチドとセラミドを含む。）で、実施例５の試験食よりも特に優れた効果があった。
In the same manner as in Example 8, a questionnaire survey for the subject person was performed. The contents of the questionnaire are as shown in Table 1. Tables 3 and 4 show the results of the questionnaire survey for the subject himself. It was confirmed that the test subject's skin condition and constipation were improved by ingesting the test meal. For the six items of [1] gloss, [2] beam, [7] texture, [11] dryness, [15] foundation paste, [17] constipation in Table 1, the test meal of Example 6 (collagen peptide and Including ceramide), there was a particularly superior effect over the test meal of Example 5.

整腸（便通）スコアの推移を表４に示した。スコア化は、「１．便秘ではない」、「２．あまり便秘ではない」、「３．どいらともいえない」、「４．やや便秘である」、「５．便秘である」の5段階で行い、各被験者における試験食の摂取前と摂取後の差を算出し、評価した。例えば、試験食の摂取前に「５．便秘である」であった被験者が、摂取後に「３．どいらともいえない」となった場合には、「整腸が「２以上」改善された」と解析した。
Table 4 shows changes in the bowel regulation (fecal bowel) score. There are five scoring levels: "1. Not constipated", "2. Not very constipated", "3. I can't say anything", "4. Somewhat constipated", "5. Constipated" The difference between before and after ingestion of the test meal in each subject was calculated and evaluated. For example, if the subject who was “5. Constipation” before taking the test meal became “3. Was analyzed.

実施例５及び６の試験食を摂取した際の皮膚（肌）の弾力性を評価した結果を図１０〜１２に示した。図１０は「整腸が「１以上」改善された」被験者、図１１は「整腸が「２以上」改善された」被験者、図１２は「整腸が「３以上」改善された」被験者の肌の弾力性を評価した結果である。整腸（便通）改善効果の高かったヒトに対して、皮膚改善効果が高いことが実証された。この傾向は、実施例６の試験食（コラーゲンペプチドとセラミドを含む。）で、実施例５の試験食よりも特に優れた効果があった。実施例５及び６の試験食を摂取することにより、肌の弾力性は増加し、肌のはりが改善された。  The results of evaluating the elasticity of the skin (skin) when the test meals of Examples 5 and 6 were ingested are shown in FIGS. FIG. 10 shows a subject whose “intestinal regulation was improved by“ 1 or more ””, FIG. 11 shows a subject whose “intestinal regulation was improved by“ 2 or more ””, and FIG. It is the result of evaluating the elasticity of the skin. It was demonstrated that the skin improvement effect was high for humans who had a high effect on improving the bowel regulation (fecal bowel movement). This tendency was particularly superior to the test meal of Example 5 in the test meal of Example 6 (including collagen peptide and ceramide). By ingesting the test meals of Examples 5 and 6, the elasticity of the skin was increased and the skin elasticity was improved.

実施例５及び６の試験食を摂取した際の肌のキメ密度を評価した結果を図１３〜１５に示した。図１３は「整腸が「１以上」改善された」被験者、図１４は「整腸が「２以上」改善された」被験者、図１５は「整腸が「３以上」改善された」被験者の肌のキメ密度を評価した結果である。整腸（便通）改善効果の高かったヒトに対して、皮膚改善効果が高いことが実証された。この傾向は、実施例４の試験食（コラーゲンペプチドとセラミドを含む。）で、実施例５の試験食よりも特に優れた効果があった。実施例５及び６の試験食を摂取することにより、肌のキメ密度は増加し、肌のキメが改善された。  The result of having evaluated the skin texture density at the time of ingesting the test meal of Example 5 and 6 was shown to FIGS. FIG. 13 shows a subject whose “intestinal regulation was improved by“ 1 or more ””, FIG. 14 shows a subject whose “intestinal regulation was improved by“ 2 or more ””, and FIG. It is the result of evaluating the texture density of the skin. It was demonstrated that the skin improvement effect was high for humans who had a high effect on improving the bowel regulation (fecal bowel movement). This tendency was particularly superior to the test meal of Example 5 in the test meal of Example 4 (including collagen peptide and ceramide). By ingesting the test meals of Examples 5 and 6, the skin texture density was increased and the skin texture was improved.

本発明によれば、天然物由来で安全性が高く、さらに皮膚（肌）改善効果及び／又は治療効果が高く、製造特性が良い乳酸菌を含有する組成物及び発酵乳を提供することができる。さらに、整腸改善効果及び／又は治療効果の高かったヒトに対して、皮膚改善効果及び／又は治療効果が高いことを特徴とする発酵乳を提供することができる。
According to the present invention, it is possible to provide a composition and fermented milk containing lactic acid bacteria that are derived from natural products, have high safety, have high skin (skin) improving effects and / or therapeutic effects, and have good production characteristics. Furthermore, fermented milk characterized by a high skin improvement effect and / or therapeutic effect can be provided to humans who have a high effect on improving the intestinal tract and / or therapeutic effect.

Claims (8)

サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、
前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０７ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、
肌の弾性力を増加させて肌のはりを改善させると共に、肌のキメ密度を増加させて肌のキメを改善させることを特徴とする皮膚改善剤。 A skin improving agent comprising Streptococcus thermophilus OLS3059 (Accession number: FERM P-15487) and / or a culture thereof as an active ingredient,
The blending concentration of the above-mentioned Thermophilus OLS3059 (Accession number: FERM P-15487) is 85 × 10 7 cfu / g or more , collagen peptide is contained at 1000 mg / 90 g or more, and ceramide is contained at 300 μg / 90 g or more. And
A skin improving agent characterized by improving skin elasticity by increasing skin elasticity and increasing skin texture density to improve skin texture. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物、並びにブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）（受託番号：ＦＥＲＭ Ｐ−１７２２７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、
前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０７ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、
肌の弾性力を増加させて肌のはりを改善させると共に、肌のキメ密度を増加させて肌のキメを改善させることを特徴とする皮膚改善剤。 Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) and / or its culture, and Bulgarian bacteria OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) (Accession number: FERM P-17227) and / Or a skin improvement agent comprising a culture thereof as an active ingredient,
The blending concentration of the above-mentioned Thermophilus OLS3059 (Accession number: FERM P-15487) is 85 × 10 7 cfu / g or more , collagen peptide is contained at 1000 mg / 90 g or more, and ceramide is contained at 300 μg / 90 g or more. And
A skin improving agent characterized by improving skin elasticity by increasing skin elasticity and increasing skin texture density to improve skin texture. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０ ７ ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、前記皮膚改善剤の摂取により整腸改善効果及び／又は治療効果が認められるヒトの皮膚の乾皮・痂皮形成、発赤・出血、組織脱落・擦り傷、浮腫、掻痒のうち、いずれか１項目以上の改善に用いられる皮膚改善剤。 A skin ameliorating agent comprising Streptococcus thermophilus OLS3059 (Accession number: FERM P-15487) and / or a culture thereof as an active ingredient, wherein the Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) ( (Contract number: FERM P-15487) is 85 × 10 7 cfu / g or more, collagen peptide is 1000 mg / 90 g or more, and ceramide is 300 μg / 90 g or more. A skin improving agent used to improve at least one of dry skin / scab formation, redness / bleeding, tissue loss / abrasion, edema, and pruritus in human skin where improvement and / or treatment effects are observed . サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物、並びにブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）（受託番号：ＦＥＲＭ Ｐ−１７２２７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０ ７ ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、前記皮膚改善剤の摂取により整腸改善効果及び／又は治療効果が認められるヒトの皮膚の乾皮・痂皮形成、発赤・出血、組織脱落・擦り傷、浮腫、掻痒のうち、いずれか１項目以上の改善に用いられる皮膚改善剤。 Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) and / or its culture, and Bulgarian bacteria OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) (Accession number: FERM P-17227) and / Or a skin improvement agent comprising a culture thereof as an active ingredient, wherein the compounding concentration of the above-mentioned Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession Number: FERM P-15487) is 85 × 10 7 cfu / g or more, collagen peptide 1000 mg / 90 g or more and ceramide 300 μg / 90 g or more At least one of the following: formation, redness / bleeding, tissue loss / abrasion, edema, pruritus Skin improving agent to be used in the good. サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物、並びにブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）（受託番号：ＦＥＲＭ Ｐ−１７２２７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、
前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０ ７ ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、
肌の弾性力を増加させて肌のはりを改善させると共に、肌のキメ密度を増加させて肌のキメを改善させることを特徴とする皮膚改善剤（ただし、発酵乳の態様からなる皮膚改善剤を除く）。 Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) and / or its culture, and Bulgarian bacteria OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) (Accession number: FERM P-17227) and / Or a skin improvement agent comprising a culture thereof as an active ingredient ,
The thermophilus bacteria OLS3059 (Streptococcus thermophilus OLS3059) (accession number: FERM P-15487) containing formulations concentration is at 85 × 10 7 cfu / g or more, the collagen peptide 1000 mg / 90 g or more, and ceramide 300 [mu] g / 90 g or more And
A skin improving agent (however, a skin improving agent consisting of a fermented milk form) that improves the skin elasticity by increasing the elasticity of the skin and improving the texture of the skin by increasing the density of the skin except for). サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）及び／又はその培養物、並びにブルガリア菌OLL1073R-1（Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1）（受託番号：ＦＥＲＭ Ｐ−１７２２７）及び／又はその培養物を有効成分として含有してなる皮膚改善剤であって、前記サーモフィルス菌 OLS3059（Streptococcus thermophilus OLS3059）（受託番号：ＦＥＲＭ Ｐ−１５４８７）の配合濃度が、８５×１０ ７ ｃｆｕ／ｇ以上で、コラーゲンペプチドを１０００ｍｇ／９０ｇ以上、及びセラミドを３００μｇ／９０ｇ以上含有し、前記皮膚改善剤の摂取により整腸改善効果及び／又は治療効果が認められるヒトの皮膚の乾皮・痂皮形成、発赤・出血、組織脱落・擦り傷、浮腫、掻痒のうち、いずれか１項目以上の改善に用いられる皮膚改善剤（ただし、発酵乳の態様からなる皮膚改善剤を除く）。 Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession number: FERM P-15487) and / or its culture, and Bulgarian bacteria OLL1073R-1 (Lactobacillus delbrueckii subspecies bulgaricus OLL1073R-1) (Accession number: FERM P-17227) and / Or a skin improvement agent comprising a culture thereof as an active ingredient , wherein the compounding concentration of the above-mentioned Thermophilus OLS3059 (Streptococcus thermophilus OLS3059) (Accession Number: FERM P-15487) is 85 × 10 7 cfu / g or more, collagen peptide 1000 mg / 90 g or more and ceramide 300 μg / 90 g or more formation, redness, bleeding, tissue falling off, abrasions, swelling, of the itching, any one or more items of Good skin improvement agent used in (except for skin improvement agents consisting aspects of fermented milk). 食品に配合することを目的とした、請求項１乃至６のいずれか一項に記載の皮膚改善剤。 The skin improvement agent according to any one of claims 1 to 6, which is intended to be blended in food . 食品に配合して発酵させることを目的とした、請求項１乃至６のいずれか一項に記載の皮膚改善剤。 The skin improving agent according to any one of claims 1 to 6, which is intended to be fermented by mixing with food .
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