JP2024065261A - Skin condition improver - Google Patents
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- JP2024065261A JP2024065261A JP2022174017A JP2022174017A JP2024065261A JP 2024065261 A JP2024065261 A JP 2024065261A JP 2022174017 A JP2022174017 A JP 2022174017A JP 2022174017 A JP2022174017 A JP 2022174017A JP 2024065261 A JP2024065261 A JP 2024065261A
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
【課題】アレルギー疾患の一つであるアトピー性皮膚炎は、遺伝的感受性、免疫および表皮バリアの機能障害、ならびに環境因子が複雑に関与して発症する皮膚の慢性炎症性疾患であり、これらの症状に対して改善効果を有し、サプリメント等として長期間継続摂取可能な乳酸菌が求められている。【解決手段】本発明者等は、乳酸菌であるラクトコッカス・ラクティスT21株を含有する食品の連続経口摂取時の皮膚計測値におよぼす影響を検討した結果、乳酸菌含有食品の連続経口摂取により、アトピー素因を有する健常成人に対する皮膚のバリア機能および明るさに関して改善効果を見出し、本発明を完成するに至った。【選択図】図１[Problem] Atopic dermatitis, an allergic disease, is a chronic inflammatory disease of the skin that develops as a result of a complex interaction of genetic susceptibility, impaired immune and epidermal barrier function, and environmental factors, and there is a demand for lactic acid bacteria that can be taken continuously over a long period of time as a supplement or the like and that have an ameliorative effect on these symptoms. [Solution] The present inventors have investigated the effect on skin measurements when continuously taking a food containing the lactic acid bacteria Lactococcus lactis T21 strain orally, and have found that continuous oral intake of a food containing lactic acid bacteria has an improving effect on the barrier function and brightness of the skin in healthy adults with a predisposition to atopy, thus completing the present invention. [Selected Figure] Figure 1
Description
本発明は、皮膚のバリア機能または明るさの改善機能を有するクランベリー由来の乳酸菌の菌株及びその菌体を含有する飲料、食品に関するものである。特に、ラクトコッカス・ラクティスに関するものである。 The present invention relates to a strain of lactic acid bacteria derived from cranberries that has the function of improving the barrier function or brightness of the skin, and to beverages and foods containing the bacteria. In particular, the present invention relates to Lactococcus lactis.
近年、アレルギー性疾患発症の増加と発症の若年化傾向が社会問題となっている。アレルギー疾患に対する根治療法として免疫療法が有望視されているが、治療法の確立までには至っていない。一方、食生活の改善から、アレルギー疾患の発症を予防し、発症者の症状を緩和できれば、強力な予防・改善手段の一つとなる。 In recent years, the increase in the incidence of allergic diseases and the trend towards younger ages of onset have become a social issue. Immunotherapy is seen as a promising method of treating allergic diseases, but no treatment has yet been established. On the other hand, if it were possible to prevent the onset of allergic diseases and alleviate the symptoms of those who develop the disease by improving their diet, this would be a powerful means of prevention and treatment.
アレルギーの発症には腸内細菌叢が深く関わっていることは知られているが、最近、その腸内細菌叢を介することなく直接、免疫賦活などの生体調節、生体防御、疾病予防、回復、老化制御に働きかけるバイオジェニックスの有効性が報告されている。 It is known that the intestinal flora is deeply involved in the onset of allergies, but recently, the effectiveness of biogenics, which acts directly on the intestinal flora without going through the intestinal flora, such as immune activation, bioregulation, biodefense, disease prevention, recovery, and aging control, has been reported.
その中で乳酸菌は、ヨーグルトなどの発酵乳製品、各種漬物類など、多くの加工飲食品において、味や風味の付与、栄養の強化、食品の保存性改善など様々な目的で用いられてきたが、さらに、乳酸菌のアレルギー抑制といった有効な生理活性について近年注目が集まっており、精力的に研究が進められている。 Among these, lactic acid bacteria have been used in many processed foods and beverages, such as fermented dairy products like yogurt and various pickles, for a variety of purposes, such as imparting flavor and aroma, enhancing nutrition, and improving food shelf life. In recent years, attention has been focused on the effective physiological activities of lactic acid bacteria, such as suppressing allergies, and research into these activities is being actively conducted.
特許文献１には「IL-12産生促進」によるアレルギー抑制作用を有する乳酸菌として、クランベリー由来の乳酸菌（ラクトコッカス・ラクティスT21株）が開示されている。 Patent Document 1 discloses cranberry-derived lactic acid bacteria (Lactococcus lactis T21 strain) as a lactic acid bacterium that has an allergy-suppressing effect by "promoting IL-12 production."
アレルギー疾患の一つであるアトピー性皮膚炎は、遺伝的感受性、免疫および表皮バリアの機能障害、ならびに環境因子が複雑に関与して発症する皮膚の慢性炎症性疾患であり、これらの症状に対して改善効果を有し、サプリメント等として長期間継続摂取可能な乳酸菌が求められている。 Atopic dermatitis, an allergic disease, is a chronic inflammatory skin disease that develops due to a complex interaction of genetic susceptibility, immune and epidermal barrier dysfunction, and environmental factors. There is a demand for lactic acid bacteria that can improve these symptoms and can be taken continuously over a long period of time as a supplement, etc.
本発明者等は、ラクトコッカス・ラクティスT21株の乳酸菌含有食品の連続経口摂取時の皮膚状態改善効果の検討を行った結果、乳酸菌含有食品の連続経口摂取により、アトピー素因を有する健常成人に対して皮膚のバリア機能および明るさに関して改善効果を見出し、本発明を完成するに至った。 The present inventors investigated the effect of continuous oral intake of a food containing Lactococcus lactis T21 strain lactic acid bacteria on improving skin conditions, and found that continuous oral intake of a food containing lactic acid bacteria improved the skin barrier function and brightness in healthy adults with a predisposition to atopy, leading to the completion of the present invention.
すなわち、本願第一の発明は、ラクトコッカス・ラクティスT21株の乳酸菌及び当該乳酸菌の発酵物を有効成分とする、経口摂取可能な皮膚状態改善剤であり、本願第二の発明は、皮膚状態の改善、すなわち皮膚のバリア機能または明るさの改善効果を含む本願第一の発明に記載の皮膚状態改善剤である。さらに、本出願人は、当該ラクトコッカス・ラクティスT21株の乳酸菌を含む皮膚状態を改善するための皮膚状態改善用医薬品・医薬部外品、または皮膚状態改善用化粧品、または皮膚状態改善用飲食品も意図している。 That is, the first invention of the present application is an orally ingestible skin condition improving agent containing Lactococcus lactis T21 strain lactic acid bacteria and a fermentation product of the lactic acid bacteria as active ingredients, and the second invention of the present application is a skin condition improving agent according to the first invention of the present application that includes an effect of improving the skin condition, i.e., improving the barrier function or brightness of the skin. Furthermore, the applicant also intends to provide a pharmaceutical product or quasi-drug for improving the skin condition, or a cosmetic product for improving the skin condition, or a food or drink for improving the skin condition, which contains the Lactococcus lactis T21 strain lactic acid bacteria.
本発明において皮膚状態の改善とは、乾燥による皮膚の経表皮水分量の減少および明るさ色差（L＊）が客観的に増したことをいう。 In the present invention, improvement of skin condition refers to an objective increase in transepidermal water content and lightness color difference (L * ) of the skin due to dryness.
本発明の乳酸菌は、乳酸菌及び乳酸菌含有食品の連続経口摂取により、アトピー素因を有する健常成人に対して皮膚のバリア機能または明るさに関して改善することが可能な皮膚改善剤、医薬品、医薬部外品、化粧品または飲食品が提供される。 The lactic acid bacteria of the present invention can be used to provide a skin improvement agent, medicine, quasi-drug, cosmetic, or food or drink that can improve the barrier function or brightness of the skin in healthy adults with a predisposition to atopy through continuous oral intake of the lactic acid bacteria and food containing the lactic acid bacteria.
以下、本発明を詳細に説明する。
１ ．ラクトコッカス・ラクティスT21株（NITE BP-02164）
本発明の乳酸菌は、ラクトコッカス・ラクティス（Lactococcus lactis） である。特にラクトコッカス・ラクティスに属する乳酸菌のうち、ラクトコッカス・ラクティスT21株である。本発明にいうT21の記号は日清食品ホールディングス株式会社で独自に菌株に付与した番号である。
The present invention will be described in detail below.
1. Lactococcus lactis T21 strain (NITE BP-02164)
The lactic acid bacteria of the present invention is Lactococcus lactis. In particular, the lactic acid bacteria of the genus Lactococcus lactis is the Lactococcus lactis T21 strain. The symbol T21 in the present invention is a number uniquely assigned to the strain by Nissin Foods Holdings Co., Ltd.
本発明のラクトコッカス・ラクティスT21株は、下記の条件で寄託されている。
（ １ ）寄託機関名：独立行政法人製品技術基盤機構 特許微生物寄託センター
（ ２ ）連絡先：〒２９２－０８１８ 千葉県木更津市かずさ鎌足２－５－８ １２２号室
（ ３ ）受託番号： ＮＩＴＥ ＢＰ－０２１６４
（ ４ ）識別のための表示：Ｔ２１
（ ５ ）原寄託日：２０１５年１１月２０日
（ ６ ）ブダペスト条約に基づく寄託への移管日：２０１６年１０月１２日
本発明のラクトコッカス・ラクティスT21株の菌学的性質は、以下の表１及び２に示す通りである。本菌学的性質は、Bergey's manual of systematic bacteriology Vol.2(1986)に記載の方法による。
The Lactococcus lactis T21 strain of the present invention has been deposited under the following conditions:
(1) Name of depository institution: National Institute of Technology and Innovation, Patent Microorganism Depositary Center (2) Contact: Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, 292-0818 (3) Accession number: NITE BP-02164
(4) Identification mark: T21
(5) Date of original deposit: November 20, 2015 (6) Date of transfer to deposit under the Budapest Treaty: October 12, 2016 The bacteriological properties of the Lactococcus lactis T21 strain of the present invention are as shown in the following Tables 1 and 2. The bacteriological properties are determined according to the method described in Bergey's manual of systematic bacteriology Vol. 2 (1986).
２．皮膚状態改善剤
本発明においては、前記ラクトコッカス属菌の乳酸菌を有効成分とする皮膚状態改善剤とすることができる。ここで、本発明にいう皮膚状態改善とは、乾燥による皮膚の経表皮水分量の減少または明るさの改善効果を奏するものをいう。
当該皮膚状態改善剤は、前記乳酸菌を発酵後の乳酸菌の菌体そのものであってもよいし、当該乳酸菌を発酵後に濃縮や分離等でエキス化及び粉末化したものであってもよい。
さらに、前記乳酸菌菌体に他の成分（例えば、糖類、タンパク質、アミノ酸、脂質、水分、ビタミン、ミネラル等）を含んでいてもよい。さらに、当該皮膚状態改善剤は、含水形態であっても乾燥形態であっても良いことは勿論である。
2. Skin condition improving agent In the present invention, the lactic acid bacteria of the genus Lactococcus may be used as an active ingredient in a skin condition improving agent. Here, the improvement of skin condition in the present invention refers to an effect of reducing transepidermal water content or improving brightness of the skin due to dryness.
The skin condition improving agent may be the lactic acid bacteria cells themselves after fermentation of the lactic acid bacteria, or may be an extract or powder of the lactic acid bacteria that has been concentrated or separated after fermentation.
Furthermore, the lactic acid bacteria cells may contain other components (e.g., sugars, proteins, amino acids, lipids, water, vitamins, minerals, etc.) Furthermore, the skin condition improving agent may, of course, be in a wet or dry form.
３．皮膚状態改善剤含有品
本発明では皮膚状態改善剤を有効成分として含む医薬品、化粧品、医薬部外品、飲食品（健康食品を含む）があげられる。
3. Products Containing a Skin Condition Improving Agent The present invention includes medicines, cosmetics, quasi-drugs, and foods and beverages (including health foods) that contain a skin condition improving agent as an active ingredient.
４．飲食品
本発明の乳酸菌は飲食品に含有せしめて使用することができる。本発明の乳酸菌は特に飲料に好適に用いることができるが、例えば、はっ酵乳及び乳酸菌飲料が考えられる。現行の乳及び乳製品の成分規格等に関する省令では、成分規格としてはっ酵乳（無脂乳固形分8.0％以上のもの）や乳製品乳酸菌飲料（無脂乳固形分3.0％以上のもの）であれば1.0×107cfu/ml以上、乳酸菌飲料（無脂乳固形分3.0％未満のもの）であれば1.0×106cfu/ml以上必要とされるが、乳などの発酵液中で増殖させたり、最終製品の形態で増殖させたりすることによって上記の菌数を実現することができる。また、はっ酵乳及び乳酸菌飲料以外にも、バター等の乳製品、マヨネーズ等の卵加工品、バターケーキ等の菓子パン類等にも利用することができる。また、即席麺やクッキー等の加工食品にも好適に利用することができる。上記の他、本発明の食品は、前記乳酸菌と共に、必要に応じて適当な担体及び添加剤を添加して製剤化された形態（例えば、粉末、顆粒、カプセル、錠剤等）であってもよい。
4. Food and drink The lactic acid bacteria of the present invention can be used by being contained in food and drink. The lactic acid bacteria of the present invention can be particularly suitably used in drinks, such as fermented milk and lactic acid bacteria drinks. The current ministerial ordinance on the compositional standards of milk and dairy products requires that the compositional standards be 1.0×10 7 cfu/ml or more for fermented milk (non-fat milk solids of 8.0% or more) and dairy lactic acid bacteria drinks (non-fat milk solids of 3.0% or more), and 1.0×10 6 cfu/ml or more for lactic acid bacteria drinks (non-fat milk solids of less than 3.0%), but the above bacterial counts can be achieved by growing them in a fermentation liquid such as milk or in the form of a final product. In addition to fermented milk and lactic acid bacteria drinks, the lactic acid bacteria can also be used in dairy products such as butter, egg products such as mayonnaise, and sweet breads such as butter cake. The lactic acid bacteria can also be suitably used in processed foods such as instant noodles and cookies. In addition to the above, the food of the present invention may be in the form of a formulation (for example, powder, granules, capsules, tablets, etc.) prepared by adding appropriate carriers and additives, if necessary, together with the lactic acid bacteria.
本発明の乳酸菌は、一般の飲料や食品以外にも特定保健用食品、機能性表示食品、栄養補助食品等に含有させることも有用である。 The lactic acid bacteria of the present invention are also useful for inclusion in general beverages and foods, as well as in foods for specified health uses, foods with functional claims, nutritional supplements, etc.
また本発明の乳酸菌は、食品以外にも化粧品分野、医薬品分野、医薬部外品、サイレージ、動物用餌、植物液体肥料等の動物飼料・植物肥料分野においても応用可能である。 In addition to food, the lactic acid bacteria of the present invention can also be used in the fields of cosmetics, pharmaceuticals, quasi-drugs, silage, animal feed, and liquid fertilizer for plants, among other animal feed and plant fertilizers.
５．医薬品
本発明の乳酸菌は、発酵後に濃縮や乾燥等でエキス化及び粉末化した上で医薬品として使用することができる。例えば、エキス化したものを瓶等に詰めたものや、発酵液乾燥粉末を賦形剤なども用いて顆粒やカプセル化、打錠し錠剤の形態として提供が可能である。
5. Pharmaceuticals The lactic acid bacteria of the present invention can be used as pharmaceuticals after being extracted and powdered by concentrating or drying after fermentation. For example, the extract can be bottled, or the dried powder of the fermentation liquid can be granulated or encapsulated using an excipient, or compressed into tablets.
本発明のクランベリー由来の乳酸菌（ラクトコッカス・ラクティスT21株）は、経口摂取した場合に皮膚のバリア機能および明るさに関して改善機能を有する。 The cranberry-derived lactic acid bacteria (Lactococcus lactis T21 strain) of the present invention has the function of improving the barrier function and brightness of the skin when taken orally.
以下、本発明の実施例を示すが、本発明は以下の実施例に限定されるものではない。 The following are examples of the present invention, but the present invention is not limited to these examples.
＜試験＞ヒト被験者に対する効果試験
乳酸菌含有食品の連続摂取による皮膚状態改善効果を検討することを目的として、皮膚の乾燥に伴うかゆみを自覚し、かつアトピー素因を有する20歳～64歳の健常男女を対象に、乳酸菌（25 mg/粒）含有食品またはプラセボ食品を1日に2粒を8週間連続摂取させる無作為化二重盲検プラセボ対照並行群間比較試験を実施した。
<Test> Efficacy test on human subjects For the purpose of investigating the effect of continuous intake of a food containing lactic acid bacteria on improving skin conditions, a randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted on healthy men and women aged 20 to 64 who were aware of itching associated with dry skin and had a predisposition to atopy. In this study, subjects were asked to take two tablets of a food containing lactic acid bacteria (25 mg/tablet) or a placebo food per day for eight consecutive weeks.
試験食品摂取群としてプラセボ食品群20名と被験食品群20名の計40名を有効性解析対象者とした。 A total of 40 people were included in the efficacy analysis, consisting of 20 people in the placebo food group and 20 people in the test food group.
＜試験食品の作製＞
試験食品として、表３に示すラクトコッカス・ラクティスT21株を含有した被験食品及びプラセボ食品を作製した。また被験食品が含有する本菌株は死菌体である。
<Preparation of test foods>
Test foods containing the Lactococcus lactis T21 strain shown in Table 3 and placebo foods were prepared as test foods. The strain contained in the test foods was killed.
＜試験方法＞
各被験者40名をプラセボ食品群20名、被験食品群20名に振り分け、各試験食品を8週間摂取させた。
<Test Method>
Forty subjects were divided into a placebo group (20 subjects) and a test food group (20 subjects), and were asked to consume each test food for eight weeks.
観察時期摂取前、摂取8週後に各被験者の皮膚計測（経表皮水分蒸散量、色差（L＊））を実施した。 Observation period: Before intake and 8 weeks after intake, each subject's skin was measured (transepidermal water loss, color difference (L * )).
皮膚計測では、経表皮水分蒸散量においてTewameter(R) TM300（Courage+Khazaka electronic GmbH）を使用し、仰臥位および側臥位にて首元を測定した。また色差（L＊）はCM-2600d（コニカミノルタジャパン株式会社）を使用し、仰臥位および側臥位にて首元を測定した。 For skin measurements, transepidermal water loss was measured at the neck in the supine and lateral positions using a Tewameter(R) TM300 (Courage+Khazaka electronic GmbH). Color difference (L * ) was measured at the neck in the supine and lateral positions using a CM-2600d (Konica Minolta Japan, Inc.).
＜結果＞
被験者の首元の経表皮水分蒸散量を摂取前と摂取後8週目に測定したところ、図１に示すように経表皮水分量の変化量が被験食品群において有意に減少し、皮膚のバリア機能の改善を示した。
<Results>
The transepidermal water loss around the subjects' necks was measured before and eight weeks after intake. As shown in Figure 1, the change in transepidermal water loss was significantly reduced in the test food group, indicating an improvement in the skin's barrier function.
被験者の首元の色差（L＊）を摂取前と摂取後8週目に測定したところ、図２に示すようにL＊値の変化量が被験食品群において有意に増加し、皮膚の明るさの改善を示した。 The color difference (L * ) around the subjects' necks was measured before and eight weeks after intake. As shown in Figure 2, the change in L * value significantly increased in the test food group, indicating an improvement in skin brightness.
このように皮膚の乾燥に伴うかゆみを自覚し、かつアトピー素因を有する20歳～64歳の健常男女を対象としたプラセボ対照二重盲検試験の結果、ラクトコッカス・ラクティスT21株の乳酸菌を主成分とする皮膚状態改善剤には、皮膚のバリア機能または明るさの改善に効果があることが確認された。 As a result of this placebo-controlled double-blind study in healthy men and women aged 20 to 64 who were aware of itching associated with dry skin and had a predisposition to atopy, it was confirmed that a skin condition improvement agent containing Lactococcus lactis T21 strain lactic acid bacteria as its main ingredient was effective in improving the skin's barrier function and brightness.
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