JP6096158B2 - Immunostimulatory or antiallergic agent - Google Patents
Immunostimulatory or antiallergic agent Download PDFInfo
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- JP6096158B2 JP6096158B2 JP2014188829A JP2014188829A JP6096158B2 JP 6096158 B2 JP6096158 B2 JP 6096158B2 JP 2014188829 A JP2014188829 A JP 2014188829A JP 2014188829 A JP2014188829 A JP 2014188829A JP 6096158 B2 JP6096158 B2 JP 6096158B2
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- salacia
- extract
- immunostimulant
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Description
本発明は、サラシア属植物の粉砕物または抽出物を含有する免疫賦活剤または抗アレルギー剤に関する。 The present invention relates to an immunostimulant or antiallergic agent containing a ground product or extract of a plant belonging to the genus Salacia.
近年、先進国おいて、花粉症や気管支喘息、アトピー性皮膚炎などに代表されるアレルギー症状は最も発症率の高い疾患の一つである。特に花粉症患者は日本だけでも約２０００万人に上るといわれており、大きな社会問題にもなっている。 In recent years, allergic symptoms such as hay fever, bronchial asthma, and atopic dermatitis are among the diseases with the highest incidence in developed countries. In particular, it is said that there are about 20 million hay fever patients in Japan alone, which is a big social problem.
花粉症にはＢ細胞から過剰産生されるアレルゲン特異的ＩｇＥ抗体、マスト細胞や好塩基球から放出されるヒスタミンやロイコトリエンと、Ｔｈ１／Ｔｈ２バランスのＴｈ２側への偏向が直接的に関与していることが知られている。体内に進入したアレルゲンは自然免疫系細胞に取り込まれて分解され、その一部の情報がＭＨＣクラスＩＩを介してＴ細胞へ提示される。抗原提示を受けたＴ細胞はＴｈ２細胞へと分化・活性化され、ＩＬ−４などのサイトカインをＢ細胞へ作用させる。Ｔｈ２細胞により刺激を受けたＢ細胞からはＩｇＥ抗体が産生され、マスト細胞や好塩基球表面に存在するＦｃレセプターに結合する。再度アレルゲンが体内に侵入してマスト細胞や好塩基球表面のＩｇＥ抗体に結合すると、細胞が脱顆粒してヒスタミンなどのケミカルメディエーターが大量に放出される上に細胞表面ではロイコトリエンなどが合成される。これら諸物質は、血管透過性を亢進させて鼻詰まりを引き起こしたり平滑筋を収縮させて気道収縮を起こす。このように近年の生活様式や食生活の変化等によりＴｈ１／Ｔｈ２バランスがＴｈ２側へ偏向することが、アレルギー疾患の増加傾向の一因となっていることが明らかになりつつある。 Pollen allergy is directly related to allergen-specific IgE antibodies overproduced from B cells, histamine and leukotrienes released from mast cells and basophils, and deviation of the Th1 / Th2 balance toward the Th2 side. It is known. Allergens that have entered the body are taken up and decomposed by innate immune system cells, and some information is presented to T cells via MHC class II. The T cell that has received the antigen is differentiated and activated into a Th2 cell, and a cytokine such as IL-4 acts on the B cell. IgE antibodies are produced from B cells stimulated by Th2 cells and bind to Fc receptors present on the surface of mast cells and basophils. When the allergen enters the body again and binds to IgE antibodies on the surface of mast cells or basophils, the cells degranulate and a large amount of chemical mediators such as histamine are released, and leukotriene is synthesized on the cell surface. . These substances enhance vascular permeability and cause nasal congestion, and contract smooth muscles to cause airway contraction. Thus, it is becoming clear that the Th1 / Th2 balance is biased toward the Th2 side due to changes in lifestyle and dietary habits in recent years contributes to the increasing tendency of allergic diseases.
現在、花粉症の症状を改善する方法としては、マスクやゴーグルや空気清浄機を使用して花粉との接触機会を少なくする方法、抗ヒスタミン薬や脱顆粒抑制能やロイコトリエン合成阻害能を有する食品、例えば甜茶やシソ葉など、を摂取する方法、アレルゲンそのものを定期的に注射することにより寛容を誘導する減感作療法などがあり、ある程度の改善効果が期待できる（非特許文献１、２、特許文献１、２参照）。
しかしながら、花粉との接触機会を少なくする方法には技術的な限界があり、抗ヒスタミン薬や減感作療法は副作用が問題視されており、既存の機能性食品には十分な効果があるとはいえず、いずれも決定的でない。
したがって、最低限、花粉に暴露しないよう日常的な清掃が推奨される一方で、Ｔｈ２偏向型の免疫系を正常な状態に戻すことでアレルギー体質を改善しつつ、ヒスタミン等の放出を抑制して花粉症等の症状を緩和できる複合的な効果を発揮する機能性食品が望まれていた。
Currently, methods for improving the symptoms of hay fever include reducing the chance of contact with pollen using a mask, goggles and air purifier, antihistamines, degranulation inhibitory and leukotriene synthesis inhibitory foods. There is a method of ingesting, for example, tea or perilla leaves, and a desensitization therapy that induces tolerance by regularly injecting allergen itself, and a certain improvement effect can be expected (Non-Patent Documents 1, 2, (See Patent Documents 1 and 2).
However, there are technical limitations in reducing the chances of contact with pollen, and antihistamines and desensitization therapy are regarded as side effects, and existing functional foods have sufficient effects. No, neither is definitive.
Therefore, daily cleaning is recommended to avoid exposure to pollen, but at the same time, the allergic constitution is improved by returning the Th2-biased immune system to a normal state, and the release of histamine and the like is suppressed. There has been a demand for a functional food that exhibits a combined effect that can relieve symptoms such as hay fever.
一方、インドやスリランカの伝統医学アーユルヴェーダにおいて天然薬物としてサラシア属植物の根や幹が利用されてきた。スリランカではサラシア・レティキュラータ（Ｓａｌａｃｉａｒｅｔｉｃｕｌａｔａ）の根皮がリュウマチ、淋病、皮膚病の治療に有効であるとともに、初期糖尿病の治療に用いられると伝承されている。インドではサラシア・オブロンガ（Ｓａｌａｃｉａｏｂｌｏｎｇａ）の根が同様の治療に用いられるほか、サラシア・キネンシス（Ｓａｌａｃｉａ ｃｈｉｎｅｎｓｉｓ）も糖尿病の治療に用いるとされており、その作用メカニズムはα−グルコシダーゼ活性阻害に基づく糖吸収抑制作用によるものであることが報告されている（非特許文献３）。 On the other hand, roots and trunks of Salacia plants have been used as natural drugs in traditional medicine Ayurveda in India and Sri Lanka. Root bark is rheumatism in Sri Lanka Salacia reticulata (Salaciareticulata), gonorrhea, together effective in the treatment of skin diseases, are handed down used in the treatment of early diabetes. In India other used for root similar treatment of Salacia oblonga (Salaciaoblonga), Salacia chinensis (Salacia chinensis) have also been used in the treatment of diabetes mellitus, its mechanism of action is sugar absorption based on α- glucosidase activity inhibition It has been reported that this is due to an inhibitory action (Non-patent Document 3).
本発明が解決しようとする課題は、長期服用しても安全な、天然物由来で副作用の少ない、免疫バランス調整や免疫賦活作用により花粉症やアトピーなどのアレルギー症状及び発がんを予防しうる食品または医薬品を提供することである。 The problem to be solved by the present invention is a food that can be safely taken for a long time, is a natural product and has few side effects, can prevent allergic symptoms such as hay fever and atopy and carcinogenesis by adjusting immune balance and immunostimulating action or carcinogenesis To provide medicinal products.
本発明者らはサラシアを摂取した際の血液への影響について鋭意検討し、その結果、サラシアは免疫賦活作用があり、更に免疫バランスを調節してアレルギーを緩和する効果があることを初めて見出した。
本発明は、具体的には下記構成よりなる。
The present inventors diligently examined the influence on blood when ingesting Salacia, and as a result, Salacia was found for the first time to have an immunostimulatory effect and to further alleviate allergies by regulating immune balance. .
Specifically, the present invention has the following configuration.
＜１＞
サラシア属植物の粉砕物または抽出物を含有することを特徴とする免疫賦活剤。
＜２＞
サラシア属植物が、サラシア・レティキュラータ（Ｓａｌａｃｉａｒｅｔｉｃｕｌａｔａ）、サラシア・オブロンガ（Ｓａｌａｃｉａ ｏｂｌｏｎｇａ）、サラシア・キネンシス（Ｓａｌａｃｉａｃｈｉｎｅｎｓｉｓ）から選ばれる少なくとも１種の植物であることを特徴とする＜１＞に記載の免疫賦活剤。
＜３＞
サラシア属植物の粉砕物または抽出物のスクラーゼの５０％阻害濃度（ＩＣ５０値）が１０μｇ／ｍｌ〜１０００μｇ／ｍｌの活性を示すことを特徴とする、＜１＞または＜２＞に記載の免疫賦活剤。
＜４＞
さらに、Ｔｏｌｌ様レセプターと結合しうる物質を含有することを特徴とする、＜１＞〜＜３＞のいずれかに記載の免疫賦活剤。
＜５＞
上記Ｔｏｌｌ様レセプターと結合しうる物質が、グルコポリサッカライド、リポポリサッカライド、およびヒアルロン酸から選ばれる少なくとも１種、またはその分解物であることを特徴とする、＜１＞〜＜４＞のいずれかに記載の免疫賦活剤。
＜６＞
＜１＞〜＜５＞のいずれかに記載の免疫賦活剤を含有する食品、または医薬品。
＜７＞
サラシア属植物の粉砕物または抽出物を含有することを特徴とする抗アレルギー剤。
<1>
An immunostimulant comprising a ground product or extract of a plant belonging to the genus Salacia.
<2>
Salacia plant, Salacia reticulata (Salaciareticulata), Salacia oblonga (Salacia oblonga), immunostimulant according to, characterized in that at least one plant selected from the Salacia chinensis (Salaciachinensis) <1> .
<3>
The immunostimulation according to <1> or <2>, wherein a 50% inhibitory concentration (IC50 value) of sucrase in a ground product or extract of a Salacia plant exhibits an activity of 10 μg / ml to 1000 μg / ml Agent.
<4>
The immunostimulator according to any one of <1> to <3>, further comprising a substance capable of binding to a Toll-like receptor.
<5>
Any of <1> to <4>, wherein the substance capable of binding to the Toll-like receptor is at least one selected from glucopolysaccharide, lipopolysaccharide, and hyaluronic acid, or a decomposition product thereof. The immunostimulant according to claim 1.
<6>
<1> -A food or a medicine containing the immunostimulator according to any one of <5>.
<7>
An antiallergic agent comprising a ground product or extract of a plant belonging to the genus Salacia.
本発明により、長期服用しても安全な、天然物由来で副作用の少ない、免疫賦活剤および抗アレルギー剤、および食品または医薬品が提供される。これを服用することで花粉症などのアレルギー症状が緩和し、免疫指標が向上しがんなどの予防効果が期待される。 INDUSTRIAL APPLICABILITY According to the present invention, an immunostimulant and an antiallergic agent, and a food or pharmaceutical product that are safe even after long-term use and are derived from natural products and have few side effects are provided. By taking this, allergic symptoms such as hay fever are alleviated, immune indices are improved, and preventive effects such as cancer are expected.
＜サラシア属植物の粉砕物または抽出物＞
本発明の免疫賦活剤または抗アレルギー剤は、サラシア属植物の粉砕物または抽出物を含有する。
サラシア属植物とは、主としてスリランカやインドや東南アジア地域に自生するニシキギ科の植物で、より具体的にはサラシア・レティキュラータ（Ｓａｌａｃｉａｒｅｔｉｃｕｌａｔａ）、サラシア・オブロンガ（Ｓａｌａｃｉａ ｏｂｌｏｎｇａ）、サラシア・プリノイデス（Ｓａｌａｃｉａｐｒｉｎｏｉｄｅｓ）、サラシア・キネンシス（Ｓａｌａｃｉａ ｃｈｉｎｅｎｓｉｓ）、サラシア・ラティフォリア（Ｓａｌａｃｉａｌａｔｉｆｏｌｉａ）、サラシア・ブルノニアーナ（Ｓａｌａｃｉａ ｂｕｒｕｎｏｎｉａｎａ）、サラシア・グランディフローラ（Ｓａｌａｃｉａｇｒａｎｄｉｆｌｏｒａ）、サラシア・マクロスペルマ（Ｓａｌａｃｉａ ｍａｃｒｏｓｐｅｒｍａ）から選ばれる１種類以上の植物が用いられ、サラシア・レティキュラータ（Ｓａｌａｃｉａｒｅｔｉｃｕｌａｔａ）、サラシア・オブロンガ（Ｓａｌａｃｉａ ｏｂｌｏｎｇａ）、サラシア・キネンシス（Ｓａｌａｃｉａｃｈｉｎｅｎｓｉｓ）から選ばれる少なくとも１種の植物であることが好ましい。
サラシア属植物の粉砕物または抽出物とは、根、幹、葉、花、果実など可食部の粉砕物、乾燥物、抽出物またはその乾燥粉末（エキス末）などを意味する。１種類以上の部位を混合して使用しても良い。より好ましくは根、幹から抽出したエキス末が用いられる。
<Crushed or extract of Salacia plants>
The immunostimulant or antiallergic agent of the present invention contains a ground product or extract of a plant of the genus Salacia.
The plant of the genus Salacia, mainly in the family Celastraceae of plants native to Sri Lanka and India and Southeast Asia, and more specifically Salacia reticulata (Salaciareticulata), Salacia oblonga (Salacia oblonga), Salacia Purinoidesu (Salaciaprinoides), Salacia chinensis (Salacia chinensis), Salacia latifolia (Salacialatifolia), Salacia Burunoniana (Salacia burunoniana), Salacia Grandiflora (Salaciagrandiflora), 1 or more plants are used selected from the Salacia macro Cum (Salacia macrosperma) , Sarashi Reticulata (Salaciareticulata), Salacia oblonga (Salacia oblonga), is preferably at least one plant selected from the Salacia chinensis (Salaciachinensis).
The pulverized product or extract of a plant belonging to the genus Salacia means a pulverized product, dried product, extract or dried powder (extract powder) of edible parts such as roots, trunks, leaves, flowers, and fruits. One or more kinds of sites may be mixed and used. More preferably, extract powder extracted from roots and trunks is used.
該エキス末は、前述の可食部等から溶媒抽出によって得られたものを乾燥させたものである。抽出溶媒としては、水、またはメタノール、エタノールを初めとするアルコール類、あるいは水とアルコール類またはアセトンなどのケトン類との混合溶媒から選択されてよい。好ましくは水、アルコール、含水アルコールを用いる。より好ましくは、抽出溶媒として熱水もしくはエタノールあるいは含水エタノールを用いる。前記含水アルコールのアルコール濃度は、３０〜９０質量％、好ましくは４０〜７０質量％の濃度のものを使用すればよい。
乾燥方法は噴霧乾燥、凍結乾燥などが挙げられるが、これに限られるものではない。
The extract powder is obtained by drying the edible portion or the like obtained by solvent extraction. The extraction solvent may be selected from water, alcohols such as methanol and ethanol, or a mixed solvent of water and alcohols or ketones such as acetone. Preferably, water, alcohol or hydrous alcohol is used. More preferably, hot water, ethanol or hydrous ethanol is used as the extraction solvent. The alcohol concentration of the hydrous alcohol may be 30 to 90% by mass, preferably 40 to 70% by mass.
Examples of the drying method include spray drying and freeze drying, but are not limited thereto.
本発明に用いるサラシア属植物の粉砕物または抽出物は、スクラーゼ５０％阻害濃度（ＩＣ５０値）が１０μｇ／ｍｌ〜１０００μｇ／ｍｌであることが好ましい。阻害活性がこの範囲にあることで、消化管からのブドウ糖吸収抑制作用が充分得られ、かつ、腹部膨満感やガスの発生を抑えられる。サラシア属植物抽出物のスクラーゼ５０％阻害濃度は１０μｇ／ｍｌ〜６００μｇ／ｍｌであることがより好ましく、１００μｇ／ｍｌ〜４５０μｇ／ｍｌであることが更に好ましい。 The ground product or extract of the plant belonging to the genus Salacia used in the present invention preferably has a sucrase 50% inhibitory concentration (IC50 value) of 10 μg / ml to 1000 μg / ml. When the inhibitory activity is in this range, a glucose absorption suppressing action from the digestive tract can be sufficiently obtained, and a feeling of fullness of the abdomen and generation of gas can be suppressed. The sucrase 50% inhibitory concentration of the Salacia plant extract is more preferably 10 μg / ml to 600 μg / ml, and even more preferably 100 μg / ml to 450 μg / ml.
スクラーゼ５０％阻害濃度（ＩＣ50値）は以下の方法で測定する。 The sucrase 50% inhibitory concentration (IC 50 value) is measured by the following method.
［実験法１］ スクラーゼＩＣ50値の測定
サンプル溶液の準備：チューブに２ｍｇのサンプル（サラシア属植物の粉砕物または抽出物）を量り取り、水２ｍＬを加えてよく懸濁し、１ｍｇ／ｍＬ濃度のサンプル溶液を作成する。これをそれぞれ０、５０、１００、２５０、５００μｇ／ｍＬとなるように水で希釈する。
基質液の準備：０．２Ｍマレイン酸バッファー（ｐＨ６．０）にスクロース濃度１００ｍＭとなるようにスクロースを溶解し、これを基質液とする。
粗酵素液の準備：１０ｍＬの生理食塩水に１ｇのｉｎｔｅｓｔｉｎａｌ ａｃｅｔｏｎｅ ｐｏｗｄｅｒ ｒａｔ（ＳＩＧＭＡ社製）を懸濁した後、遠心分離（３，０００ｒｐｍ，４℃，５ｍｉｎ）した。得られた上清を分離し、粗酵素液とする。
前述の各濃度のサンプル溶液５００μＬに対し、基質液４００μＬを添加し、水浴中３７℃にて５分間予備加温した。ここにそれぞれ、粗酵素液を１００μＬ添加し、３７℃にて６０分間反応させた。反応終了後、９５℃にて２分間加温することで酵素を失活させて反応を停止させた。生成したグルコース濃度を市販のキット・ムタロターゼ・グルコースオキシダーゼ法（グルコースＣＩＩテストワコー、和光純薬工業（株））を使用して定量を行う。
ブランクの準備：前述の各濃度のサンプル溶液２５０μＬに対し、基質液２００μＬ、粗酵素液５０μＬを添加し、直ちに９５℃にて２分間加温することで酵素を熱失活させ、ブランクデータとする。
得られた値より検量線を作成し、酵素活性を５０％阻害する濃度（ＩＣ50値）を求める。
[Experimental method 1] Preparation of sample solution for measurement of sucrase IC 50 value: Weigh 2 mg of sample (crushed or extract of Salacia plant) into a tube, add 2 mL of water and suspend well, and add 1 mg / mL concentration. Make a sample solution. This is diluted with water to 0, 50, 100, 250, and 500 μg / mL, respectively.
Preparation of substrate solution: Sucrose is dissolved in 0.2 M maleate buffer (pH 6.0) to a sucrose concentration of 100 mM, and this is used as a substrate solution.
Preparation of crude enzyme solution: 1 g of an intestinal acetone powder rat (manufactured by SIGMA) was suspended in 10 mL of physiological saline, followed by centrifugation (3,000 rpm, 4 ° C., 5 min). The obtained supernatant is separated to obtain a crude enzyme solution.
400 μL of the substrate solution was added to 500 μL of the sample solution having each concentration described above, and pre-warmed at 37 ° C. for 5 minutes in a water bath. 100 μL of the crude enzyme solution was added to each, and reacted at 37 ° C. for 60 minutes. After completion of the reaction, the enzyme was inactivated by heating at 95 ° C. for 2 minutes to stop the reaction. The produced glucose concentration is quantified using a commercially available kit, mutarotase / glucose oxidase method (glucose CII test Wako, Wako Pure Chemical Industries, Ltd.).
Blank preparation: 200 μL of substrate solution and 50 μL of crude enzyme solution are added to 250 μL of the sample solution of each concentration described above, and the enzyme is heat-inactivated by immediately heating at 95 ° C. for 2 minutes to obtain blank data. .
A calibration curve is prepared from the obtained values, and the concentration at which the enzyme activity is inhibited by 50% (IC 50 value) is determined.
免疫賦活剤または抗アレルギー剤の１日あたりの摂取量または目安摂取量を設定する場合は、免疫賦活剤または抗アレルギー剤１日摂取量中のサラシア属植物の粉砕物または抽出物の量として、例えばＩＣ50値が５０μｇ／ｍｌのサラシア属植物抽出物を用いる場合、１０〜６００ｍｇが好ましく、４０〜４５０ｍｇがより好ましく、５０〜３５０ｍｇが特に好ましい。 When setting the daily intake or guideline intake of the immunostimulant or antiallergic agent, as the amount of ground or extract of Salacia plant in the daily intake of the immunostimulant or antiallergic agent, For example, when a Salacia plant extract having an IC 50 value of 50 μg / ml is used, 10 to 600 mg is preferable, 40 to 450 mg is more preferable, and 50 to 350 mg is particularly preferable.
免疫賦活剤または抗アレルギー剤中の好ましいサラシア属植物の量は、上記の１日あたりの好ましい量より適宜計算できる。例えば、１日摂取量が３錠の錠剤を作製した場合、1錠あたり１日量の１／３を含有することが好ましい。すなわち、サラシア属植物の粉砕物または抽出物を好ましくは３〜２００ｍｇ、より好ましくは１３〜１５０ｍｇ、特に好ましくは１７〜１１７ｍｇ含有する。 The preferable amount of the plant belonging to the genus Salacia in the immunostimulant or the antiallergic agent can be appropriately calculated from the above preferable amount per day. For example, when a tablet with a daily intake of 3 tablets is prepared, it is preferable to contain 1/3 of the daily dose per tablet. That is, it contains preferably 3 to 200 mg, more preferably 13 to 150 mg, and particularly preferably 17 to 117 mg of a ground product or extract of a plant belonging to the genus Salacia.
また、下記の式１で求められる値が、０．５以上であることが好ましく、０．８以上であることがより好ましく、１．７以上であることが特に好ましい。
免疫賦活剤または抗アレルギー剤全体としてのＩＣ50値は、式２で求められる値として、０．１〜７．５が好ましく、０．１５〜４．５０がより好ましく、０．３〜３．７５が特に好ましい。
Moreover, it is preferable that the value calculated | required by following formula 1 is 0.5 or more, It is more preferable that it is 0.8 or more, It is especially preferable that it is 1.7 or more.
The IC 50 value of the immunostimulant or antiallergic agent as a whole is preferably 0.1 to 7.5, more preferably 0.15 to 4.50, and more preferably 0.3 to 3. 75 is particularly preferred.
［式１］
免疫賦活剤または抗アレルギー剤１日摂取量中のサラシア属植物抽出物（ｍｇ）／ＩＣ50値（μｇ／ｍｌ）
［式２］
免疫賦活剤または抗アレルギー剤質量（ｍｇ）／ＩＣ50値（μｇ／ｍｌ）
[Formula 1]
Immunostimulant or antiallergic agent Salacia plant extract in daily intake (mg) / IC 50 value (μg / ml)
[Formula 2]
Immunostimulant or antiallergic agent mass (mg) / IC 50 value (μg / ml)
前記サラシア属植物の粉砕物または抽出物が、抽出物中全量に対してマンジフェリンを０．８質量％以上含有することが好ましく、１〜３０質量％含有することがより好ましく、３．０〜１１質量％以上含有することが特に好ましい。また、本発明の免疫賦活剤または抗アレルギー剤のマンジフェリン含量は、１日摂取量中に、１ｍｇ以上が好ましく、１．８〜５４ｍｇより好ましく、５．５〜１９ｍｇが特に好ましい。 The pulverized product or extract of the plant belonging to the genus Salacia preferably contains 0.8% by mass or more, more preferably 1 to 30% by mass of mangiferin based on the total amount in the extract, 3.0 to It is particularly preferable to contain 11% by mass or more. Further, the mandiferin content of the immunostimulant or antiallergic agent of the present invention is preferably 1 mg or more, more preferably 1.8 to 54 mg, and particularly preferably 5.5 to 19 mg in the daily intake.
マンジフェリンは実験法２により測定できる。
［実験法２］ マンジフェリン含量の測定
マンジフェリンの含有量はＨＰＬＣを用いて、以下の方法で測定する。
＜ＨＰＬＣ条件＞
カラム： Ｃａｐｃｅｌｌｐａｃｋ Ｃ１８ ＵＧ１２０ φ４．６×２５０ｍｍ（資生堂）
カラム温度： ４０℃
検出： ＵＶ３６０
流速： １．０ｍＬ／ｍｉｎ
溶媒Ａ： １．０％ 酢酸 溶媒Ｂ： メタノール
リニアグラジエント（％Ｂ）： １５％（０ｍｉｎ）→２５％（２０ｍｉｎ）
サンプルは５０％メタノールに溶解させた後、シリンジフィルターで不溶物を除去して調製する。
検出されたマンジフェリンのピーク面積から、標品の検量線を用いて含有量を算出する。
Mangiferin can be measured by Experimental Method 2.
[Experiment Method 2] Measurement of Mangiferin Content The content of mangiferin is measured by the following method using HPLC.
<HPLC conditions>
Column: Capcellpack C18 UG120 φ4.6 × 250mm (Shiseido)
Column temperature: 40 ° C
Detection: UV360
Flow rate: 1.0 mL / min
Solvent A: 1.0% Acetic acid Solvent B: Methanol linear gradient (% B): 15% (0 min) → 25% (20 min)
The sample is prepared by dissolving in 50% methanol and then removing insolubles with a syringe filter.
The content is calculated from the detected peak area of mangiferin using a standard curve of the standard.
＜Ｔｏｌｌ様レセプターと結合しうる物質＞
本発明の免疫賦活剤または抗アレルギー剤は、さらに、生体内のマクロファージ表面に存在するＴｏｌｌ様レセプター（ＴＬＲ）と結合・反応しうる物質を含有することが好ましい。
そのような物質としては、ＴＬＲ２と結合・反応しうる物質、ＴＬＲ４と結合・反応する物質が好ましく、それら両方を含有していることが更に好ましい。
ＴＬＲ２と結合・反応しうる物質としては、βグルカンなどのグルコポリサッカライドまたはそれを含有する酵母類、乳酸菌類、リポペプチド類、リポタイコ酸、リポアラビノマンナンなどが挙げられ、βグルカン（β１，３−グルカン）がより好ましい。βグルカンは植物由来、菌類由来、細菌由来など特に限定されないが、キノコ類（たとえばアガリクス、霊芝、メシマコブ）や酵母類（たとえばパン酵母、ビール酵母）などの菌類由来のものがより好ましい。
ＴＬＲ４と結合・反応しうる物質としては、ヒアルロン酸またはその分解物、ヒアルロン酸オリゴマー、リポポリサッカライドまたはそれを含むグラム陰性菌、マンナン類などが挙げられる。
Ｔｏｌｌ様レセプターと結合しうる物質がＴＬＲに結合するとサイトカイン（インターフェロン、ＴＮＦ−α）の産生、ＣＤ４０、ＣＤ８０、ＣＤ８６、ＭＨＣクラスＩＩの表出増加などマクロファージが活性化することが知られている。
Ｔｏｌｌ様レセプターと結合しうる物質は、グルコポリサッカライド、リポポリサッカライド、およびヒアルロン酸から選ばれる少なくとも１種、またはその分解物であることが好ましい。
<Substance capable of binding to Toll-like receptor>
The immunostimulant or antiallergic agent of the present invention preferably further contains a substance capable of binding and reacting with a Toll-like receptor (TLR) present on the surface of macrophages in vivo.
As such a substance, a substance capable of binding and reacting with TLR2 and a substance capable of binding and reacting with TLR4 are preferable, and it is more preferable that both of them are contained.
Examples of substances capable of binding and reacting with TLR2 include glucopolysaccharides such as β-glucan or yeasts containing the same, lactic acid bacteria, lipopeptides, lipoteichoic acid, lipoarabinomannan and the like, and β-glucan (β1, 3-glucan) is more preferable. β-glucan is not particularly limited such as plant-derived, fungal-derived, or bacterial-derived, but those derived from fungi such as mushrooms (for example, agaricus, ganoderma, mesimacob) and yeasts (for example, baker's yeast, beer yeast) are more preferable.
Examples of substances that can bind to and react with TLR4 include hyaluronic acid or its degradation products, hyaluronic acid oligomers, lipopolysaccharides, gram-negative bacteria containing them, and mannans.
It is known that when a substance capable of binding to a Toll-like receptor binds to TLR, macrophages are activated such as production of cytokines (interferon, TNF-α), increased expression of CD40, CD80, CD86, and MHC class II.
The substance that can bind to the Toll-like receptor is preferably at least one selected from glucopolysaccharide, lipopolysaccharide, and hyaluronic acid, or a degradation product thereof.
Ｔｏｌｌ様レセプターと結合しうる物質は、ナノスケールオーダーまで分散していることが好ましい。具体的には、平均粒子径が１ｎｍ〜１０００ｎｍの乳化物（エマルション）または固体分散物（サスペンジョン）であることが好ましく、平均粒子径はより好ましくは５ｎｍ〜２００ｎｍである。
また、本発明において「高濃度エマルション」とはＴｏｌｌ様レセプターと結合しうる物質の含有量が０．１％質量以上のエマルジョン組成物を示す。本発明の高濃度エマルジョンの平均粒子径は２００ｎｍ以上であることが好ましく、より好ましくは３００〜１００００ｎｍ以上である。
乳化物の粒子径は、粒度分布計等で計測することができる。
The substance that can bind to the Toll-like receptor is preferably dispersed to the nanoscale order. Specifically, an emulsion (emulsion) or a solid dispersion (suspension) having an average particle size of 1 nm to 1000 nm is preferable, and an average particle size is more preferably 5 nm to 200 nm.
In the present invention, “high-concentration emulsion” refers to an emulsion composition having a content of a substance capable of binding to a Toll-like receptor of 0.1% by mass or more. The average particle size of the high-concentration emulsion of the present invention is preferably 200 nm or more, more preferably 300 to 10,000 nm or more.
The particle diameter of the emulsion can be measured with a particle size distribution meter or the like.
乳化物は、公知の乳化物調製方法にて調製することができ、例えば「乳化・可溶化の技術」（辻著、工業図書（株）発行）の６５−６６頁、９２−１０５頁に記載されており、凝集法・分散法のいずれも好ましく用いられる。また、「食品用乳化剤 第２版」（日高 著、幸書房発行）の８８−９０頁記載のように、（１）自己乳化法、（２）セッケン生成法、（３）単純乳化法、（４）転送乳化法、（５）界面活性剤法乳化法と分類されるいずれの方法も好ましいが、特に、高濃度エマルジョンの調製には、単純乳化法または界面活性剤法乳化法が好ましく、界面活性剤法乳化法が特に好ましい。Ｔｏｌｌ様レセプターと結合しうる物質の乳化物は、本発明の高濃度エマルジョンを経由して調製されることが好ましい。固体分散物についてはせん断や高圧粉砕などの破砕法や、酵素分解、熱分解、加水分解、乳化重合のような反応を介する方法にて調製されることが好ましい。
界面活性剤法乳化法により本発明の高濃度エマルションを経由して調製する場合は、エマルション組成物となる溶液に高濃度エマルションを攪拌しながら添加することにより調製することができる。この場合の希釈倍率は、５〜１０００倍が好ましく、１０〜２００倍がより好ましい。
Emulsions can be prepared by known emulsion preparation methods, and are described, for example, on pages 65-66 and 92-105 of “Emulsification / Solubilization Technology” (Issue, published by Kogyosho Co., Ltd.). Both of the aggregation method and the dispersion method are preferably used. In addition, as described on pages 88-90 of "Emulsifier for Foods 2nd Edition" (published by Hidaka, published by Sachishobo), (1) self-emulsification method, (2) soap production method, (3) simple emulsification method, Any method classified as (4) transfer emulsification method and (5) surfactant method emulsification method is preferable, but in particular, for the preparation of high-concentration emulsion, simple emulsification method or surfactant method emulsification method is preferable, The surfactant method emulsification method is particularly preferred. An emulsion of a substance that can bind to a Toll-like receptor is preferably prepared via the high-concentration emulsion of the present invention. The solid dispersion is preferably prepared by a crushing method such as shearing or high-pressure pulverization, or a method via a reaction such as enzymatic decomposition, thermal decomposition, hydrolysis, or emulsion polymerization.
In the case of preparing via the high-concentration emulsion of the present invention by the surfactant method emulsification method, it can be prepared by adding the high-concentration emulsion to the solution to be the emulsion composition while stirring. In this case, the dilution factor is preferably 5 to 1000 times, and more preferably 10 to 200 times.
Ｔｏｌｌ様レセプターと結合しうる物質の分子量は、１００〜８００万が好ましい。より好ましくは、１０００〜１００万であり、分子量３０００〜３０万であることが更に好ましい。
Ｔｏｌｌ様レセプターと結合しうる物質は通常、１日摂取量として１〜２０００ｍｇ摂取することが好ましく、５０ｍｇ〜１０００ｍｇが更に好ましい。
Ｔｏｌｌ様レセプターと結合しうる物質は、免疫賦活剤または抗アレルギー剤中、０．１質量％〜９５質量％含有されていることが好ましく、０．５質量％〜７０質量％含有されていることがより好ましく、１質量％〜５０質量％含有されていることがさらに好ましい。
Ｔｏｌｌ様レセプターと結合しうる物質は、各種市販品を用いてもよく、通常の方法で合成されたものを用いても良い。
The molecular weight of the substance that can bind to the Toll-like receptor is preferably from 1 to 8 million. More preferably, it is 1000-1 million, and it is still more preferable that it is molecular weight 3000-300,000.
In general, the substance capable of binding to a Toll-like receptor is preferably taken in an amount of 1 to 2000 mg, more preferably 50 to 1000 mg as a daily intake.
The substance capable of binding to the Toll-like receptor is preferably contained in the immunostimulant or antiallergic agent in an amount of 0.1% by mass to 95% by mass, and 0.5% by mass to 70% by mass. Is more preferable, and it is further more preferable that 1 mass%-50 mass% are contained.
As the substance capable of binding to the Toll-like receptor, various commercially available products may be used, or those synthesized by a usual method may be used.
＜その他成分＞
本発明の免疫賦活剤または抗アレルギー剤は、更に他の成分を含有していてもよく、例えば、乳酸菌、ミネラル酵母、フラボノイドやポリフェノール等を含有していてもよい。
<Other ingredients>
The immunostimulant or antiallergic agent of the present invention may further contain other components, for example, lactic acid bacteria, mineral yeast, flavonoids, polyphenols, and the like.
乳酸菌類は、ヒトを含む哺乳動物に経口的に投与することができ、生体消化管内で有用な作用を発揮する菌であることが好ましい。 Lactic acid bacteria can be administered orally to mammals including humans, and are preferably bacteria that exhibit useful effects in the living digestive tract.
より具体的には、宿主に対して無害で、胃酸や胆汁酸に比較的耐性があり、生体腸内に定着性を有して乳酸を産生し、腸内微生物叢を整える作用を有するものが望ましい。かかる有用乳酸菌類としては、例えばアシドフィルス乳酸桿菌（Ｌａｃｔｏｂａｃｉｌｌｕｓａｃｉｄｏｐｈｉｌｕｓ）、ビフィズス菌（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ ｌｏｎｇｕｍ等）、フェカリス菌（Ｓｔｒｅｐｔｏｃｏｃｃｕｓｆａｅｃａｌｉｓ）、レウテリ乳酸桿菌（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｒｅｕｔｅｒｉ）、カセイ乳酸桿菌（Ｌａｃｔｏｂａｃｉｌｌｕｓｃａｓｅｉ）、プランタラム菌（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｐｌａｎｔａｒｕｍ）、フェルメンタム乳酸桿菌（Ｌａｃｔｏｂａｃｉｌｌｕｓｆｅｒｍｅｎｔｕｍ）、ラムノサス乳酸桿菌（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｒｈａｍｎｏｓｕｓ）、アギルス乳酸桿菌（Ｌａｃｔｏｂａｃｉｌｌｕｓａｇｉｌｉｓ）、ガセリ菌（Ｌａｃｔｏｂａｃｉｌｌｕｓ ｇａｓｓｅｒｉ）、メセンテリカス菌（Ｂａｃｉｌｌｕｓｍｅｓｅｎｔｅｒｉｃｕｓ）、酪酸菌（Ｃｌｏｓｔｒｉｄｉｕｍ ｂｕｔｙｒｉｃｕｍ）又はそれらのサブスピーシーズ等を例示することができるが、好ましくはアシドフィルス菌（Ｌａｃｔｏｂａｃｉｌｌｕｓａｃｉｄｏｐｈｉｌｕｓ）、ビフィズス菌（Ｂｉｆｉｄｏｂａｃｔｅｒｉｕｍ ｌｏｎｇｕｍ等）、フェカリス菌（Ｓｔｒｅｐｔｏｃｏｃｃｕｓｆａｅｃａｌｉｓ）であり、これらの乳酸菌類は１種単独若しくは２種以上を適宜組み合わせて使用することができる。 More specifically, those that are harmless to the host, are relatively resistant to gastric acid and bile acids, have a fixability in the living intestine, produce lactic acid, and act to regulate the intestinal microflora. desirable. Such useful lactic acid bacteria, for example acidophilus Lactobacillus (Lactobacillusacidophilus), bifidobacterium (Bifidobacterium longum, etc.), faecalis (Streptococcusfaecalis) reuteri Lactobacillus (Lactobacillus reuteri), caustic lactobacilli (Lactobacilluscasei), Lactobacillus plantarum (Lactobacillus plantarum ), Fell lactofermentum lactobacilli (Lactobacillusfermentum) rhamnosus Lactobacillus (Lactobacillus rhamnosus), Agirusu lactobacilli (Lactobacillusagilis) gasseri bacteria (Lactobacillus Asseri), Mesenterikasu bacteria (Bacillusmesentericus), can be exemplified butyric acid bacteria (Clostridium butyricum) or their subsp like, preferably Lactobacillus acidophilus (Lactobacillusacidophilus), bifidobacterium (Bifidobacterium longum, etc.), faecalis (Streptococcusfaecalis) These lactic acid bacteria can be used singly or in appropriate combination of two or more.
これらの乳酸菌類は、生菌であれば取得の由来は特に制限されず、簡便には商業的に市販されているものを広く用いることができる。 As long as these lactic acid bacteria are live bacteria, the origin of acquisition is not particularly limited, and those commercially available can be used widely.
本発明に用いる乳酸菌類の量は、免疫賦活剤または抗アレルギー剤の１日あたりの摂取量または目安摂取量を設定する場合、免疫賦活剤または抗アレルギー剤１日量中の乳酸菌類の生菌数として、１０００万個〜１０００億個が好ましく、５０００万個〜５００億個がより好ましく、１〜１００個が特に好ましい。 The amount of lactic acid bacteria used in the present invention is a live bacterium of the lactic acid bacteria in the daily dose of the immunostimulant or antiallergic agent when the daily intake or guideline intake of the immunostimulant or antiallergic agent is set. The number is preferably 10 million to 100 billion, more preferably 50 million to 50 billion, and particularly preferably 1 to 100.
ミネラル酵母とは、ミネラルを含有する酵母を意味する。ミネラルとしては、ナトリウム（Ｎａ）、カリウム（Ｋ）、クロール（Ｃｌ）、カルシウム（Ｃａ）、マグネシウム（Ｍｇ）、リン（Ｐ）、硫黄（Ｓ）および、微量元素と呼ばれる鉄（Ｆｅ）、亜鉛（Ｚｎ）、銅（Ｃｕ）、マンガン（Ｍｎ）、コバルト（Ｃｏ）、クロム（Ｃｒ）、ヨウ素（Ｉ）、モリブデン（Ｍｏ）、セレン（Ｓｅ）の１６種の金属元素が挙げられる。本発明に用いるミネラル酵母としては、クロムを含有するクロム酵母が好ましい。酵母の種類に特に制限はないが、パン酵母またはビール酵母が好ましい。
クロム酵母のクロム含有量は、クロム酵母１００質量部に対し、０．０１〜５質量部が好ましく、０．０５〜１質量部がより好ましく、０．１〜０．３質量部が特に好ましい。
免疫賦活剤または抗アレルギー剤中のクロム酵母含有量は、免疫賦活剤または抗アレルギー剤１００質量部に対し、３〜５質量部が好ましく、１〜１０質量部がより好ましく、０．５〜５０質量部が特に好ましい。
１日の摂取量または目安摂取量を設定する場合、免疫賦活剤または抗アレルギー剤１日量中のクロム酵母量として、５〜５００ｍｇが好ましく、１０〜１００ｍｇがより好ましく、３０〜５０ｍｇが特に好ましい。免疫賦活剤または抗アレルギー剤１日量中のクロムの量としては、２０〜２００μｇが好ましく、４０〜１５０μｇがより好ましく、６０〜１００μｇが特に好ましい。
Mineral yeast means yeast containing mineral. As minerals, sodium (Na), potassium (K), chlor (Cl), calcium (Ca), magnesium (Mg), phosphorus (P), sulfur (S), and iron (Fe), zinc called trace elements There are 16 metal elements such as (Zn), copper (Cu), manganese (Mn), cobalt (Co), chromium (Cr), iodine (I), molybdenum (Mo), and selenium (Se). As the mineral yeast used in the present invention, chromium yeast containing chromium is preferable. Although there is no restriction | limiting in particular in the kind of yeast, Baker's yeast or beer yeast is preferable.
The chromium content of the chrome yeast is preferably 0.01 to 5 parts by mass, more preferably 0.05 to 1 part by mass, and particularly preferably 0.1 to 0.3 part by mass with respect to 100 parts by mass of the chrome yeast.
The chromium yeast content in the immunostimulant or antiallergic agent is preferably 3 to 5 parts by mass, more preferably 1 to 10 parts by mass, and more preferably 0.5 to 50 parts per 100 parts by mass of the immunostimulant or antiallergic agent. Part by mass is particularly preferred.
When setting the daily intake or the standard intake, the amount of chromium yeast in the daily dose of the immunostimulant or antiallergic agent is preferably 5 to 500 mg, more preferably 10 to 100 mg, and particularly preferably 30 to 50 mg. . The amount of chromium in the daily dose of the immunostimulant or antiallergic agent is preferably 20 to 200 μg, more preferably 40 to 150 μg, and particularly preferably 60 to 100 μg.
フラボノイドは、植物の全器官に存在する色素成分の総称であり、主に果実や野菜に含まれ、特に、緑葉や白色野菜、柑橘類の皮の中に配糖体の形で存在する。
本発明において、フラボノイドとは、植物に広く含まれる色素成分の総称で、特に、野菜や果実に多く含まれるフラバン誘導体を意味する。
Flavonoids are a general term for pigment components present in all organs of plants, and are mainly contained in fruits and vegetables, and are particularly present in the form of glycosides in the leaves of green leaves, white vegetables and citrus fruits.
In the present invention, the flavonoid is a general term for pigment components widely contained in plants, and particularly means a flavan derivative contained in a large amount in vegetables and fruits.
フラボノイドとしては、フラボノール類、イソフラボン類およびカテキン類が好ましい。フラボノール類は、ポリフェノール類として知られている。
フラボノイドは体内に摂取される物質であるが、一般に吸収しにくい。しかしながら、フラボノイドは少量でも有効であり、強力な抗酸化物質であるため、発ガン物質の活性を抑制したり、血行促進作用や抗血栓作用があることが知られている。
Flavonoids are preferably flavonols, isoflavones and catechins. Flavonols are known as polyphenols.
Flavonoids are substances ingested by the body, but are generally difficult to absorb. However, since flavonoids are effective even in a small amount and are strong antioxidants, it is known that they inhibit the activity of carcinogens, have blood circulation promoting action and antithrombotic action.
本発明において、フラボノイドは茶、ブドウ、タマネギなどの各由来物から得ることができる。ここで、由来物とは、生体の少なくとも一部から抽出されるものを意味する。抽出には、例えば、上記サラシア属植物の抽出物を調製する方法が適用され、抽出物の形態も上記と同様のものが可能であり、例えば、抽出後の濾液のままで、または濃縮もしくは希釈した状態またはその乾燥粉末の形態で、あるいはそれらの混合物のいずれの形態であってもよい。
カテキン類を含む茶抽出物は、ツバキ科の常緑樹である茶の木より作製する。茶の木は、インドやスリランカ、東南アジアで栽培されているアッサミカと中国や日本で栽培されているカメリア・シネンシスのどちらも用いられる。抽出には、通常、好ましくは水、アルコール、含水アルコールを用いる。より好ましくは、抽出溶媒として熱水もしくはエタノールあるいは含水エタノールを用いる。前記含水アルコールのアルコール濃度は、３０〜９０質量％、好ましくは４０〜７０質量％の濃度のものを使用すればよい。乾燥方法は噴霧乾燥、凍結乾燥などが挙げられるが、これに限られるものではない。
In the present invention, flavonoids can be obtained from various sources such as tea, grapes and onions. Here, the term “derived” means a substance extracted from at least a part of the living body. For the extraction, for example, a method for preparing an extract of the above-mentioned Salacia genus plant is applied, and the form of the extract can be the same as described above. For example, the filtrate after extraction or the concentrated or diluted form can be used. Or in the form of its dry powder, or any mixture thereof.
A tea extract containing catechins is prepared from a tea tree, which is an evergreen tree of the camelliaceae family. The tea tree used is either Assamika cultivated in India, Sri Lanka or Southeast Asia, or Camellia sinensis cultivated in China or Japan. In the extraction, usually, water, alcohol or hydrous alcohol is preferably used. More preferably, hot water, ethanol or hydrous ethanol is used as the extraction solvent. The alcohol concentration of the hydrous alcohol may be 30 to 90% by mass, preferably 40 to 70% by mass. Examples of the drying method include spray drying and freeze drying, but are not limited thereto.
茶抽出物中には、ポリフェノールやカテキン類などの抗酸化物質を含有する。カテキン、エピカテキン、ガロカテキン、エピガロカテキン、カテキンガレート、エピカテキンガレート、ガロカテキンガレートまたはエピガロカテキンガレートが含まれていることが好ましく、特に、エピガロカテキンガレートを含有することが好ましい。
本発明の免疫賦活剤または抗アレルギー剤は、該茶抽出物を、０．１〜４０質量％含有することが好ましく、０．５〜３５質量％含有することが更に好ましく、１．０〜３０質量％含有することが特に好ましい。
The tea extract contains antioxidants such as polyphenols and catechins. Catechin, epicatechin, gallocatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate or epigallocatechin gallate is preferably included, and epigallocatechin gallate is particularly preferable.
The immunostimulant or antiallergic agent of the present invention preferably contains 0.1 to 40% by mass of the tea extract, more preferably 0.5 to 35% by mass, and more preferably 1.0 to 30%. It is particularly preferable to contain it by mass%.
また、フラボノイドのひとつであるフラボノール類は、活性酸素を除去し、動脈硬化の抑制や血流改善等の抗酸化作用を示す。フラボノール類の中でも、ポリフェノールのひとつであるレスベラトロールが抗酸化物質として着目されている。レスベラトロールは、スチルベン骨格から構成されており、ブドウの果皮に多く含まれ、そのため、ブドウから作られる赤ワインにも含有されている。
本発明は、該フラボノール類を成分として含む、ブドウエキスまたはブドウ酒濃縮物を含有することが好ましい。
本発明の免疫賦活剤または抗アレルギー剤は、ブドウ抽出物を、０．１〜３０質量％含有することが好ましく、０．１〜１０質量％を含有することが更に好ましい。
Further, flavonols, which are one of flavonoids, remove active oxygen and exhibit an antioxidant action such as suppression of arteriosclerosis and improvement of blood flow. Among the flavonols, resveratrol, one of polyphenols, has attracted attention as an antioxidant. Resveratrol is composed of a stilbene skeleton, and is contained in grape skins, and is therefore also contained in red wine made from grapes.
The present invention preferably contains a grape extract or a wine concentrate containing the flavonols as a component.
The immunostimulant or antiallergic agent of the present invention preferably contains 0.1 to 30% by mass of grape extract, more preferably 0.1 to 10% by mass.
レスベラトロールは、脂肪を燃焼させる働きがあり、血管系の疾患である動脈硬化防止や、抗ガン作用、また、ＤＮＡの細胞***による短化を防ぎ、カロリー制限をしたのと同様の細胞延命効果があり、生活習慣病予防素材として優れた効果を持つことがわかっている。 Resveratrol has the function of burning fat, preventing arteriosclerosis, which is a disease of the vascular system, preventing cancer, shortening due to DNA cell division, and prolonging cell life similar to that of calorie restriction. It is effective and is known to have excellent effects as a lifestyle-related disease prevention material.
本発明の免疫賦活剤または抗アレルギー剤におけるレスベラトロールの含有量は、０．０００１〜５．００質量％が好ましく、更には、０．００１〜２．００質量％が好ましい。 The content of resveratrol in the immunostimulant or antiallergic agent of the present invention is preferably 0.0001 to 5.00% by mass, and more preferably 0.001 to 2.00% by mass.
また、フラボノール類の中でも、ポリフェノールであるケルセチンが抗酸化物質として着目されている。ケルセチンは、フラバン構造を有しており、タマネギの外皮に多く含まれる。 Among flavonols, quercetin, which is a polyphenol, has attracted attention as an antioxidant. Quercetin has a flavan structure and is abundant in the onion skin.
ケルセチンは、ビタミンＣの吸収サポート、抗酸化作用、免疫作用等の生理作用が報告されており、さらには、脂肪吸収抑制に有効であることがわかっており、生活習慣病予防素材として優れた効果を持つことがわかっている。 Quercetin has been reported to have physiological effects such as vitamin C absorption support, antioxidant action, immune action, etc., and it has been shown to be effective in suppressing fat absorption, and has excellent effects as a lifestyle-related disease prevention material. I know I have
本発明の免疫賦活剤または抗アレルギー剤におけるケルセチンの含有量は、０．００１〜１５質量％が好ましく、更には、０．０５〜１０質量％が好ましく、更には、０．１〜５．０質量％が好ましい。 The content of quercetin in the immunostimulant or antiallergic agent of the present invention is preferably 0.001 to 15% by mass, more preferably 0.05 to 10% by mass, and further 0.1 to 5.0%. Mass% is preferred.
本発明の免疫賦活剤または抗アレルギー剤は、特にカテキンを１〜５０質量％含有することが好ましい。カテキンとしては、緑茶由来のもの等が特に好ましい。
また、本発明の免疫賦活剤または抗アレルギー剤は、リパーゼ活性阻害効果を有するポリフェノール類を２〜８０質量％含有することが好ましい。リパーゼ活性阻害効果を有するポリフェノールとしては、烏龍茶由来のもの、ブドウ由来のもの、リンゴ由来のもの、ライチ由来のもの、松樹皮由来のもの、カンカ由来のもの等が特に好ましい。
In particular, the immunostimulant or antiallergic agent of the present invention preferably contains 1 to 50% by mass of catechin. As catechins, those derived from green tea are particularly preferred.
Moreover, it is preferable that the immunostimulant or antiallergic agent of this invention contains 2-80 mass% of polyphenols which have a lipase activity inhibitory effect. As polyphenols having a lipase activity inhibitory effect, those derived from oolong tea, grapes, apples, lychees, pine bark, kanka and the like are particularly preferred.
＜使用方法・製剤＞
本発明の免疫賦活剤または抗アレルギー剤はヒトを含む哺乳類を対象とし、該哺乳類に経口的に投与される。本発明の免疫賦活剤または抗アレルギー剤は、食品（飲料を含む）、食品材料、医薬部外品、医薬品、医薬品材料、医薬部外品材料であってもよい。他の成分としては、経口投与剤として薬学的若しくは食品衛生上許容される各種の担体、例えば賦形剤、滑沢剤、安定剤、分散剤、結合剤、希釈剤、香味料、甘味料、風味剤、着色剤などを例示することができる。
<Usage and formulation>
The immunostimulant or antiallergic agent of the present invention is intended for mammals including humans and is orally administered to the mammals. The immunostimulant or antiallergic agent of the present invention may be food (including beverages), food materials, quasi drugs, pharmaceuticals, pharmaceutical materials, and quasi drugs. Other components include various carriers that are pharmaceutically or food hygienically acceptable for oral administration, such as excipients, lubricants, stabilizers, dispersants, binders, diluents, flavoring agents, sweeteners, A flavoring agent, a coloring agent, etc. can be illustrated.
本発明の免疫賦活剤または抗アレルギー剤の形態は、本発明の効果を奏するものである限り特に制限されず、例えば、錠剤、丸剤、顆粒剤、細粒剤、咀嚼剤、カプセル剤（ハードカプセル、ソフトカプセルに充填されたもの）、液剤、チュアブル剤、飲料等が挙げられる。その他の食品の形態であってもよい。 The form of the immunostimulant or antiallergic agent of the present invention is not particularly limited as long as it exhibits the effects of the present invention. For example, tablets, pills, granules, fine granules, chewing agents, capsules (hard capsules) , Filled in soft capsules), liquids, chewables, beverages and the like. Other food forms may be used.
これらの投与形態は、当該分野で通常知られた慣用的な方法を用いて調製することができる。 These dosage forms can be prepared using conventional methods commonly known in the art.
なお、錠剤、丸剤及び顆粒剤の場合、必要に応じて慣用的な剤皮を施した剤形、例えば糖衣錠，ゼラチン被包剤、腸溶被包剤、フィルムコーティング剤等とすることもでき、また錠剤は二重錠等の多層錠とすることもできる。 In the case of tablets, pills and granules, a dosage form with a conventional coating can be used as necessary, for example, sugar-coated tablets, gelatin encapsulating agents, enteric encapsulating agents, film coating agents and the like. The tablet may be a multilayer tablet such as a double tablet.
本発明の免疫賦活剤または抗アレルギー剤には、上記の他にビタミン、ビタミン様物質、タンパク質、アミノ酸、油脂、有機酸、炭水化物、植物由来原料、動物由来原料、微生物、食品用添加物、医薬品用添加物等、経口摂取可能な成分を適宜含有させることができる。 In addition to the above, the immunostimulant or antiallergic agent of the present invention includes vitamins, vitamin-like substances, proteins, amino acids, fats and oils, organic acids, carbohydrates, plant-derived materials, animal-derived materials, microorganisms, food additives, pharmaceuticals Ingredients that can be taken orally, such as additives for use, can be contained as appropriate.
本発明の免疫賦活剤または抗アレルギー剤の摂取により、血清中のＩＦＮ−γが増大し、免疫バランスが改善される。また、腸管免疫器官を有する盲腸の質量が増大し盲腸上皮細胞中のリンパ球数が増加し、免疫が賦活される。これにより、花粉症やアトピーなどのアレルギー症状の緩和や、風邪の予防、発がんの予防が期待される。
本発明の免疫賦活剤または抗アレルギー剤は、飲食可能な天然物であるサラシア属植物由来のものであり、長期服用しても安全であり、副作用が少ない。
By ingesting the immunostimulant or antiallergic agent of the present invention, IFN-γ in serum increases and the immune balance is improved. In addition, the mass of the cecum having intestinal tract immune organs increases, the number of lymphocytes in the cecal epithelial cells increases, and immunity is activated. This is expected to alleviate allergic symptoms such as hay fever and atopy, prevent colds, and prevent carcinogenesis.
The immunostimulant or antiallergic agent of the present invention is derived from a plant of the genus Salacia, which is a natural product that can be eaten and consumed, and is safe even when taken for a long time and has few side effects.
以下に実施例を用いて本発明について説明するが、本発明は以下の実施例に限定されるものではない。 Hereinafter, the present invention will be described using examples, but the present invention is not limited to the following examples.
（実験例１）
サラシア・レチキュラータ（Ｓ． ｒｅｔｉｃｕｌａｔａ）とサラシア・オブロンガ（Ｓ．ｏｂｌｏｎｇａ）の根及び幹の部分を粉砕後等重量ずつ混合し、９８℃の熱水抽出工程を経て得られた液をスプレー乾燥し、サラシアエキス末１を得た。サラシアエキス末１のスクラーゼＩＣ５０値は４１であった。
Ｗｉｓｔａｒ系雄性ラット（６週齢、体重約２００ｇ）を７日間予備飼育後、５匹づつ表１に示す投与群に分け飼育した。投与は各水溶液（１００ｍｇ／ｍｌ液）を胃ゾンデを用いて行い、コントロールは同量の水を投与した。
(Experimental example 1)
The roots and stems of Salacia reticulata and Salacia oblonga ( S. oblonga ) were mixed by equal weight after pulverization, and the liquid obtained through the hot water extraction process at 98 ° C. was spray-dried, Salacia extract powder 1 was obtained. The sucrase IC 50 value of Salacia extract powder 1 was 41.
Wistar male rats (6 weeks old, body weight about 200 g) were reared for 7 days, and then 5 rats were divided into the administration groups shown in Table 1 and reared. Administration was carried out for each aqueous solution (100 mg / ml solution) using a stomach tube, and the same amount of water was administered as a control.
表１中、投与量はラット体重１ｋｇあたりに投与する１日量を示す。βグルカンはアルブロン社製「ピュアホワイト」、低分子ヒアルロン酸は株式会社中原製のもの（分子量１０万以下）を使用した。 In Table 1, the dosage represents the daily dosage administered per kg body weight of the rat. β-glucan “Pure White” manufactured by Albron Co., Ltd., and low molecular hyaluronic acid manufactured by Nakahara Co., Ltd. (molecular weight of 100,000 or less) were used.
飼育８週間後にエーテル麻酔下で開腹し、腹大動脈より血液を採取して免疫学的指標であるＩＦＮ−γを測定した（コスモ・バイオ株式会社製 ｒａｔ ＩＦＮ−γ ＥＬＩＳＡを使用）。
また、剖検を行い各器官の質量測定および病理組織学検査を行った。
各投与群の比較結果から、差の大きかったＩＦＮ−γ、盲腸質量、盲腸上皮細胞中のリンパ球数の結果を表１に示す。なお、値は各群５匹の平均値をコントロール群を１００とした時の相対値として示した。
After 8 weeks of breeding, the abdomen was opened under ether anesthesia, blood was collected from the abdominal aorta, and IFN-γ as an immunological index was measured (using rat IFN-γ ELISA manufactured by Cosmo Bio Inc.).
In addition, autopsy was performed, and mass measurement and histopathological examination of each organ were performed.
Table 1 shows the results of IFN-γ, cecal mass, and number of lymphocytes in the cecal epithelial cells, which showed large differences from the comparison results of each administration group. In addition, the value was shown as a relative value when an average value of 5 animals in each group was defined as 100 as a control group.
実験例１の結果、本発明の実施例は比較例と比較して血清中のＩＦＮ−γが顕著に増大しており、免疫バランスが改善されていることがわかった。また、腸管免疫器官を有する盲腸の質量が増大し盲腸上皮細胞中のリンパ球数が対象群に対し顕著に増えており、免疫賦活の効果があることがわかった。
なお、試験期間中各群間での体重は差が見られず、肝機能や腎機能などの異常についても見られなかった。
As a result of Experimental Example 1, it was found that in the examples of the present invention, IFN-γ in serum was remarkably increased as compared with Comparative Examples, and the immune balance was improved. In addition, the mass of the cecum having intestinal tract immune organs increased, and the number of lymphocytes in the cecal epithelial cells significantly increased with respect to the subject group, indicating that there was an effect of immunostimulation.
During the study period, there was no difference in body weight between the groups, and no abnormalities such as liver function or kidney function were observed.
（実験例２）
サラシア・キネンシス（Ｓａｌａｃｉａ ｃｈｉｎｅｎｓｉｓ）の根及び幹の部分を粉砕後、４０℃のエタノール水（エタノール３０体積％）による抽出工程を経て得られた液にデキストリンを加えてスプレー乾燥し、サラシアエキス末２（デキストリン含有率３０質量％）を得た。
このサラシアエキス末を用いて表１の試料１〜８の配合をした粉末を作成し、また試料１錠あたりのスクラーゼＩＣ５０値を［実験法１］記載の方法で測定した。
これらを用いて以下の表２に示す配合成分を打錠し、試料７〜１２を作成した。
被験者の服用量は表２の試料を３錠／日で設定した。βグルカンはアルブロン社製「ピュアホワイト」、低分子ヒアルロン酸は株式会社中原製のもの（分子量１０万以下）、結晶セルロースは旭化成ケミカルズ社製「セオラスＦＤ−１０１」を使用した。
(Experimental example 2)
After crushing the roots and trunks of Salacia chinensis , dextrin is added to the liquid obtained through the extraction step with ethanol water (ethanol 30% by volume) at 40 ° C. and spray dried, and Salacia extract powder 2 (Dextrin content 30% by mass) was obtained.
The Salacia extract powder was used to create a powder blending of the sample 1-8 in Table 1, was also measured sucrase an IC 50 value per sample 1 tablet by the method described [Experimental Method 1].
Using these, the ingredients shown in Table 2 below were tableted to prepare Samples 7-12.
The dose of the subject was set at 3 tablets / day for the sample in Table 2. β-glucan “Pure White” manufactured by Albron Co., Ltd., low molecular hyaluronic acid manufactured by Nakahara Co., Ltd. (molecular weight of 100,000 or less), and crystalline cellulose “Seolus FD-101” manufactured by Asahi Kasei Chemicals Co., Ltd. were used.
通年性のアレルギー鼻炎患者３０名に十分なインフォームドコンセントを行った後、５名ずつのグループに、試料７〜１２をそれぞれ毎日の食後３０分以内に１錠経口摂取してもらい、それを３０日間繰り返した。摂取期間の終了後、鼻炎症状に関し下記の基準により効果を評価してもらい各群で平均値を算出した。
点数 評価基準
０ ほとんど症状に変化なし
１ 症状が少し改善した
２ 症状が改善した
３ 症状がかなり改善した
結果を表２に示す。
After thorough informed consent was given to 30 patients with perennial allergic rhinitis, each group of 5 had to take 1 tablet of Samples 7 to 12 orally within 30 minutes after each meal. Repeated for days. After the ingestion period, the average value was calculated for each group by evaluating the effect of nasal inflammation according to the following criteria.
Score Evaluation criteria 0 Almost no change in symptom 1 Symptom improved slightly 2 Symptom improved 3 Table 2 shows the result of significant improvement in symptom.
実験例２の結果から、本発明の実施例は比較例と比較して顕著な鼻炎症状の改善が見られた。この効果はスクラーゼＩＣ５０値が１０００より小さい時に顕著であり、またβグルカンと併用することによって更に効果が増進されることがわかった。 From the results of Experimental Example 2, the Example of the present invention showed a marked improvement in nasal inflammation compared to the Comparative Example. This effect is remarkable when the sucrase IC 50 value is less than 1000, and it has been found that the effect is further enhanced by the combined use with β-glucan.
（実験例３） （サラシアエキス末を使用した錠剤）
表３に示す配合により、錠剤を作成しシェラックコーティングを施したサプリメントを作成した。サラシアエキス末１は上記実験例１のもの、その他の各成分は下記のものを使用した。
・緑茶抽出物：太陽化学製 サンフェノン１００ｓ（カテキン５５質量％含有）
・タマネギ外皮抽出物：太邦（株）製
・ヘマトコッカス藻色素：武田紙器（株）製ＡＳＴＯＴＳ−Ｓ（アスタキサンチン類含有率２０質量％）
・クロム酵母：ＬＡＬＬＥＭＡＮＤ ＢＩＯ−ＩＮＧＲＥＤＩＥＮＴＳ（クロム０．２質量％以上含有） ＬＡＬＬＥＭＡＮＤ社製）
・ショ糖ラウリン酸エステル：リョートーシュガーエステルＬ−１６９５：三菱化学フーズ（株）製
・カルニチン：伊藤ライフサイエンス（株）製
(Experimental example 3) (Tablet using Salacia extract powder)
Tablets were prepared according to the formulation shown in Table 3, and supplements with shellac coating were prepared. Salacia extract powder 1 was used in Experimental Example 1, and the other components were as follows.
Green tea extract: Taiyo Kagaku Sunphenon 100s (contains 55% catechin)
-Onion hull extract: manufactured by Taiko Co., Ltd.-Haematococcus alga pigment: ASTOTS-S manufactured by Takeda Shiki Co., Ltd. (astaxanthin content 20% by mass)
・ Chromium yeast: LALLEMAND BIO-INGREDIENTS (containing 0.2% by mass or more of chromium) manufactured by LALLEMAND)
・ Sucrose laurate: Ryoto sugar ester L-1695: Mitsubishi Chemical Foods Co., Ltd. Carnitine: Ito Life Science Co., Ltd.
杉花粉の飛散する直前の２月（場所：小田原市）に、杉花粉症の既往症がある成人１０名に十分なインフォームドコンセントを行った後、表３の錠剤をそれぞれ毎日の食後３０分以内に１錠経口摂取してもらいそれを６０日間繰り返して、杉花粉飛散後の影響について調べた。
その結果、この配合の錠剤摂取でも実施例２で示された効果が得られた。更に、摂取被験者より、便秘が解消した、身体が軽くなった、風邪をひきにくくなったなどの報告を得た。
In February (place: Odawara City) just before the cedar pollen was scattered, after giving sufficient informed consent to 10 adults with a history of cedar pollinosis, each tablet in Table 3 was within 30 minutes after each meal. 1 tablet was orally ingested and repeated for 60 days to examine the effects of cedar pollen scattering.
As a result, the effect shown in Example 2 was obtained even when the tablet of this composition was ingested. In addition, the subjects ingested reports that constipation was resolved, the body was lightened, and it was difficult to catch a cold.
（実験例４） （サラシアエキス末２を使用したドリンク）
表４の成分を混合、溶解し飲料液を調製した。これを５０ｃｃずつ瓶に充填し８５℃で１０分間加熱殺菌し、これを室温まで冷却し飲料とした。
杉花粉の飛散する直前の２月（場所：小田原市）に、杉花粉症の既往症がある成人１０名に十分なインフォームドコンセントを行った後、表４のドリンクをそれぞれ毎日の食後３０分以内に１本経口摂取してもらいそれを６０日間繰り返して、杉花粉飛散後の影響について調べた。
各成分は上記実験例１〜３と同様のものを使用した。
(Experimental example 4) (Drink using Salacia extract powder 2)
The ingredients in Table 4 were mixed and dissolved to prepare a beverage. 50 cc of this was filled into bottles and sterilized by heating at 85 ° C. for 10 minutes, and this was cooled to room temperature to obtain a beverage.
In February (place: Odawara City), just before the cedar pollen was scattered, after giving sufficient informed consent to 10 adults with a history of cedar pollinosis, the drinks in Table 4 were each within 30 minutes after each meal. Was taken orally and repeated for 60 days to examine the effects after cedar pollen scattering.
Each component used the same thing as the said Experimental Examples 1-3.
この配合の飲料摂取でも実施例２で示された効果が得られた。更に、摂取被験者より、腹囲が減少した、身体が軽くなった、二日酔いしにくくなったなどの報告を得た。 The effects shown in Example 2 were obtained even when this beverage was ingested. In addition, the subjects reported that the waist circumference decreased, the body became light, and it became difficult to get a hangover.
Claims (10)
Ｔｏｌｌ様レセプターと結合しうる物質が、βグルカンおよびヒアルロン酸から選ばれる少なくとも１種であり、
サラシア属植物が、サラシア・オブロンガ（Salacia obonga）、サラシア・レティキュラータ（Salacia reticulata）、サラシア・プリノイデス（Salacia prinoides）から選ばれた少なくとも一種であり、サラシア属植物の抽出物のスクラーゼ５０％阻害濃度（ＩＣ５０値）が１０μｇ／ｍｌ〜６００μｇ／ｍｌの活性を示し、リンパ球数を増加することによって免疫を賦活化する免疫賦活剤。 An immunostimulant comprising a ground or extract of a Salacia plant and a substance capable of binding to a Toll-like receptor,
The substance capable of binding to the Toll-like receptor is at least one selected from β-glucan and hyaluronic acid,
The plant of the genus Salacia is at least one selected from Salacia obonga, Salacia reticulata, Salacia prinoides, and 50% inhibitory concentration of sucrase in the extract of the genus Salacia ( immunostimulant which activating immunity by IC50 value) indicates the activity of 10μg / ml~600μg / ml, to increase the number of lymphocytes.
Ｔｏｌｌ様レセプターと結合しうる物質が、βグルカンおよびヒアルロン酸から選ばれる少なくとも１種であり、
サラシア属植物が、サラシア・オブロンガ（Salacia obonga）、サラシア・レティキュラータ（Salacia reticulata）、サラシア・プリノイデス（Salacia prinoides）から選ばれた少なくとも一種であり、サラシア属植物の抽出物のスクラーゼ５０％阻害濃度（ＩＣ５０値）が１０μｇ／ｍｌ〜６００μｇ／ｍｌの活性を示し、血清中のＩＦＮ−γの増大により免疫バランスを改善することでアレルギーを抑える抗アレルギー剤。 An antiallergic agent comprising a ground or extract of a Salacia plant and a substance capable of binding to a Toll-like receptor,
The substance capable of binding to the Toll-like receptor is at least one selected from β-glucan and hyaluronic acid,
The plant of the genus Salacia is at least one selected from Salacia obonga, Salacia reticulata, Salacia prinoides, and 50% inhibitory concentration of sucrase in the extract of the genus Salacia ( IC50 value) is an antiallergic agent that exhibits an activity of 10 μg / ml to 600 μg / ml and suppresses allergy by improving immune balance by increasing IFN-γ in serum.
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