JP2021093995A - Composition for ameliorating obesity and composition for ameliorating type ii diabetes - Google Patents

Composition for ameliorating obesity and composition for ameliorating type ii diabetes Download PDF

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JP2021093995A
JP2021093995A JP2019229206A JP2019229206A JP2021093995A JP 2021093995 A JP2021093995 A JP 2021093995A JP 2019229206 A JP2019229206 A JP 2019229206A JP 2019229206 A JP2019229206 A JP 2019229206A JP 2021093995 A JP2021093995 A JP 2021093995A
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rice bran
thermolysin
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耕作 大日向
Kosaku Ohinata
耕作 大日向
尚久 正箱
Naohisa Masahako
尚久 正箱
雄太郎 小川
Yutaro Ogawa
雄太郎 小川
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Sunstar Inc
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Abstract

To provide a composition for ameliorating obesity with excellent obesity-ameliorating effect, and a composition for ameliorating type II diabetes with excellent type II diabetes-ameliorating effect.SOLUTION: A composition for ameliorating obesity and a composition for ameliorating type II diabetes of the present invention contains a thermolysin processed product of rice bran. The thermolysin processed product may contain at least one kind selected from the group selected from sequence number 1 and Leu-Arg-Ala. The thermolysin processed product is produced by processing squeezed/defatted rice bran by thermolysin, and may be water-soluble fraction.SELECTED DRAWING: None

Description

本発明は、米糠由来の成分を含有する肥満改善用組成物及びII型糖尿病改善用組成物に関する。 The present invention relates to a composition for improving obesity and a composition for improving type II diabetes, which contains a component derived from rice bran.

一般に、米糠は、玄米を精米する過程で得られる果皮、種皮、胚芽等が集合した組成物であり、古くから米糠油の原料、糠漬けの糠床等として用いられてきた。また、米糠には、抗腫瘍作用、抗酸化作用等を有するフィチン酸及びフェルラ酸、更年期障害改善作用、紫外線吸収作用等を有するγ−オリザノール等の有用な成分が含まれていることが知られている。したがって、従来より米糠は、栄養価の高い健康食品の他、医薬品、化粧料等の原料にも用いられてきた。 In general, rice bran is a composition obtained by gathering pericarp, seed coat, germ, etc. obtained in the process of milling brown rice, and has been used as a raw material for rice bran oil, a bran bed pickled in bran, and the like for a long time. It is also known that rice bran contains useful components such as phytic acid and ferulic acid having antitumor activity and antioxidant activity, and γ-oryzanol having climacteric disorder improving activity and ultraviolet absorbing activity. ing. Therefore, rice bran has traditionally been used as a raw material for pharmaceuticals, cosmetics, etc., in addition to highly nutritious health foods.

また、近年、例えば特許文献1,2に開示されるように、米糠に特定のプロテアーゼを作用させることにより、ACE阻害活性等の生体に有用な作用の向上効果が見出されるようになった。 Further, in recent years, as disclosed in Patent Documents 1 and 2, for example, by allowing a specific protease to act on rice bran, an effect of improving an action useful for a living body such as an ACE inhibitory activity has been found.

特許第6296722号公報Japanese Patent No. 6296722 特許第6462100号公報Japanese Patent No. 6462100

本発明の目的とするところは、肥満改善作用に優れる肥満改善用組成物を提供することにある。また、別の目的とするところは、II型糖尿病の改善作用に優れるII型糖尿病改善用組成物を提供することにある。 An object of the present invention is to provide an obesity-improving composition having an excellent obesity-improving effect. Another object of the present invention is to provide a composition for improving type II diabetes, which is excellent in improving type II diabetes.

本発明は、米糠のサーモリシン処理物が優れた肥満の改善作用及びII型糖尿病の改善作用を発揮することを見出したことに基づく発明である。
上記目的を達成するために、本発明の一態様の肥満改善用組成物は、米糠のサーモリシン処理物を含むことを特徴とする。
The present invention is based on the finding that a thermolysin-treated product of rice bran exerts an excellent effect of improving obesity and an effect of improving type II diabetes.
In order to achieve the above object, the composition for improving obesity according to one aspect of the present invention is characterized by containing a thermolysin-treated product of rice bran.

前記サーモリシン処理物は、配列番号1及びLeu−Arg−Alaから選ばれる少なくとも一種を含んでもよい。
前記サーモリシン処理物は、圧搾脱脂米糠をサーモリシン処理したものであって、水溶性画分であってもよい。
The thermolysin-treated product may contain at least one selected from SEQ ID NO: 1 and Leu-Arg-Ala.
The thermolysin-treated product is a thermolysin-treated product of pressed degreased rice bran and may be a water-soluble fraction.

前記肥満改善は、白色脂肪組織の減少であってもよい。
本発明の別の態様のII型糖尿病改善用組成物は、米糠のサーモリシン処理物を含むことを特徴とする。
The improvement in obesity may be a decrease in white adipose tissue.
The composition for improving type II diabetes of another aspect of the present invention is characterized by containing a thermolysin-treated product of rice bran.

前記II型糖尿病改善は、糖代謝の改善又はインスリン抵抗性の改善であってもよい。 The improvement in type II diabetes may be an improvement in glucose metabolism or an improvement in insulin resistance.

本発明によれば、優れた肥満改善作用を発揮できる。また、本発明によれば、優れたII型糖尿病の改善作用を発揮できる。 According to the present invention, an excellent obesity improving effect can be exhibited. Further, according to the present invention, it is possible to exert an excellent effect of improving type II diabetes.

各試験グループの個体群における7〜25週齢までの体重変化を示すグラフ。Graph showing body weight change from 7 to 25 weeks of age in the population of each test group. 各試験グループの個体群における試験食の摂取量を示すグラフ。The graph which shows the intake of the test meal in the population of each test group. 糖負荷試験における各試験グループの個体群の血糖値の変化を示すグラフ。The graph which shows the change of the blood glucose level of the population of each test group in a glucose tolerance test. インスリン負荷試験における各試験グループの個体群の血糖値レベルの変化を示すグラフ。The graph which shows the change of the blood glucose level of the population of each test group in an insulin tolerance test. 各試験グループの個体群における白色脂肪組織の質量を示すグラフ。The graph which shows the mass of white adipose tissue in the population of each test group. 各試験グループの個体群における褐色脂肪組織の質量を示すグラフ。The graph which shows the mass of brown adipose tissue in the population of each test group. 各試験グループの個体群における肝臓の質量を示すグラフ。The graph which shows the mass of the liver in the population of each test group.

(第1実施形態)
以下、本発明の肥満改善用組成物を具体化した第1実施形態を説明する。本実施形態の肥満改善用組成物に含まれる米糠のサーモリシン処理物の原料に用いられる米糠は、特に限定されないが、例えば米糠そのものであってもよく、脱脂米糠が適用されてもよい。脱脂米糠としては、例えば圧搾により脱脂された圧搾脱脂米糠、有機溶媒を用いて抽出処理された抽出脱脂米糠等が挙げられる。これらの原料の中で圧搾脱脂米糠が好ましい。圧搾脱脂米糠の製造方法としては、例えばまず搗精後に得られた米糠(生米糠)を加熱することでリパーゼを失活させ(リパーゼ失活処理)、さらに圧搾処理する方法が挙げられる。
(First Embodiment)
Hereinafter, the first embodiment in which the composition for improving obesity of the present invention is embodied will be described. The rice bran used as a raw material for the thermolysin-treated rice bran contained in the composition for improving obesity of the present embodiment is not particularly limited, but may be, for example, rice bran itself or defatted rice bran may be applied. Examples of the defatted rice bran include squeezed defatted rice bran degreased by pressing, extracted defatted rice bran extracted using an organic solvent, and the like. Among these raw materials, squeezed defatted rice bran is preferable. Examples of the method for producing squeezed degreased rice bran include a method in which lipase is inactivated by first heating rice bran (raw rice bran) obtained after polishing (lipase inactivation treatment), and then squeezing treatment is performed.

リパーゼ失活処理は、18〜20質量%程度の脂質を含有する米糠(生米糠)の酸化劣化を防ぐ目的で行われる。通常、生米糠を70〜130℃程度で加熱焙煎することにより行われる。圧搾処理は、公知の圧搾法、例えば加熱焙煎処理され100〜115℃程度になった米糠を低温連続圧搾機(例えばテクノシグマ社製の商品名:ミラクルチャンバー)により圧搾する方法を適用できる。圧搾は、圧搾後の脱脂米糠中の脂質が5〜20質量%程度となるまで行うことが好ましい。また、リパーゼ失活処理前の米糠や搾油後の脱脂米糠の水分含量を低減させる等の目的で乾燥処理を行ってもよい。更に、特に圧搾脱脂米糠は、公知の方法により粉砕、分級し、粉末状とすることが好ましい。この際、粉末の平均粒子径は、5〜200μmが好ましく、10〜150μmがより好ましく、40〜100μmが最も好ましい。平均粒子径は、篩法により測定できる。なお、脱脂米糠中の脂質含量は、特に限定されないが、5〜20質量%が好ましく、7〜15質量%がより好ましい。なお、脱脂米糠は、市販品を使用してもよい。市販品としては、例えば商品名ハイブレフ(サンブラン社製)等が挙げられる。 The lipase inactivation treatment is carried out for the purpose of preventing oxidative deterioration of rice bran (raw rice bran) containing about 18 to 20% by mass of lipid. Usually, it is carried out by heating and roasting raw rice bran at about 70 to 130 ° C. As the squeezing treatment, a known squeezing method, for example, a method of squeezing rice bran that has been heat roasted to about 100 to 115 ° C. with a low temperature continuous squeezing machine (for example, a trade name: Miracle Chamber manufactured by TechnoSigma) can be applied. The squeezing is preferably carried out until the lipid content in the defatted rice bran after squeezing is about 5 to 20% by mass. Further, the drying treatment may be carried out for the purpose of reducing the water content of the rice bran before the lipase deactivation treatment and the degreased rice bran after the oil extraction. Further, it is particularly preferable that the squeezed degreased rice bran is pulverized and classified by a known method to form a powder. At this time, the average particle size of the powder is preferably 5 to 200 μm, more preferably 10 to 150 μm, and most preferably 40 to 100 μm. The average particle size can be measured by the sieving method. The lipid content in the defatted rice bran is not particularly limited, but is preferably 5 to 20% by mass, more preferably 7 to 15% by mass. As the degreased rice bran, a commercially available product may be used. Examples of commercially available products include the trade name Hi-Bleff (manufactured by Saint-Blanc).

サーモリシンは、バチルス・サーモプロテオライティクス由来の中性金属プロテアーゼであり、EC番号は3.4.24.27である。サーモリシンは、上記微生物より抽出精製したものを使用してもよく、生化学的に合成したものを使用してもよく、また、市販品を使用してもよい。市販品としては、例えばペプチド研究所社製、和光純薬工業社製等が挙げられる。 Thermolysin is a neutral metalloproteinase derived from Bacillus thermoproteolitics and has an EC number of 3.4.24.27. As the thermolysin, one extracted and purified from the above-mentioned microorganism may be used, one biochemically synthesized may be used, or a commercially available product may be used. Examples of commercially available products include those manufactured by Peptide Institute, Ltd., Wako Pure Chemical Industries, Ltd., and the like.

サーモリシン処理物を得るための処理条件としては、サーモリシンの活性が得られる条件であれば、特に制限はされず、例えば温度、pH、時間等の諸条件を適宜設定できる。処理方法としては、例えば米糠原料に溶液として水を加え、必要によりpH調整を行った後、所定量のサーモリシンが添加される。サーモリシンの添加量は、処理条件、原料との比率、酵素の力価等を考慮し、適宜設定できる。サーモリシン処理時の米糠原料は、米糠原料としての米糠又は脱脂米糠をそのまま適用してもよく、米糠原料の水抽出物(水溶性画分)を適用してもよい。米糠原料の水抽出物は、米糠原料を水で抽出処理して得られた液体組成物(水及び抽出された米糠成分からなる)である。水抽出条件は、特に制限されないが、例えば10〜50℃程度の水に米糠原料を1〜24時間程度浸漬(又は撹拌)する方法が例示される。 The treatment conditions for obtaining the thermolysin-treated product are not particularly limited as long as the thermolysin activity can be obtained, and various conditions such as temperature, pH, and time can be appropriately set. As a treatment method, for example, water is added as a solution to the rice bran raw material, the pH is adjusted if necessary, and then a predetermined amount of thermolysin is added. The amount of thermolysin added can be appropriately set in consideration of the treatment conditions, the ratio with the raw material, the titer of the enzyme, and the like. As the rice bran raw material at the time of the thermolysin treatment, rice bran or defatted rice bran as the rice bran raw material may be applied as it is, or a water extract (water-soluble fraction) of the rice bran raw material may be applied. The water extract of the rice bran raw material is a liquid composition (composed of water and the extracted rice bran component) obtained by extracting the rice bran raw material with water. The water extraction conditions are not particularly limited, and examples thereof include a method of immersing (or stirring) the rice bran raw material in water at about 10 to 50 ° C. for about 1 to 24 hours.

サーモリシンの処理条件としては、例えば米糠原料及びサーモリシンを水に混合したうえ、37℃前後で穏やかに撹拌しながら10〜30時間程度反応させることで処理を行うことができる。当該処理後、サーモリシンを失活させてもよい。サーモリシンの失活処理は、例えば加熱(例えば100℃、10〜20分程度の処理)等により行うことができる。 As the treatment conditions for thermolysin, for example, rice bran raw material and thermolysin can be mixed with water and reacted at about 37 ° C. with gentle stirring for about 10 to 30 hours. After the treatment, the thermolysin may be inactivated. The deactivation treatment of thermolysin can be performed, for example, by heating (for example, treatment at 100 ° C. for about 10 to 20 minutes).

サーモリシン処理物は、上述したように米糠をサーモリシンにより処理して得られた組成物であり、サーモリシンにより低分子化した米糠由来のタンパク質の分解物(特にペプチド)を含む組成物である。かかるペプチドとしては、約10kDa以下のものが含まれることが好ましい。より具体的には、配列番号1(Val−Tyr−Thr−Pro−Gly)及びLeu−Arg−Alaから選ばれる少なくとも一種を含むことがより好ましい。 The thermolysin-treated product is a composition obtained by treating rice bran with thermolysin as described above, and is a composition containing a decomposition product (particularly a peptide) of a protein derived from rice bran whose molecular weight is reduced by thermolysin. Such peptides preferably include those of about 10 kDa or less. More specifically, it more preferably contains at least one selected from SEQ ID NO: 1 (Val-Tyr-Thr-Pro-Gly) and Leu-Arg-Ala.

なお、サーモリシン処理後の処理液について、油分が含まれる場合には、さらに米糠タンパク質分解物が含まれる水溶性画分を取り出すことが好ましい。かかる水溶性画分には肥満改善作用及び後述するII型糖尿病改善作用を発揮する成分が含まれている。水溶性画分は、サーモリシン処理後の処理液を例えば遠心分離することにより得られる。また、サーモリシン処理後の処理液は、濾過を行って不溶性画分を除いた濾液として回収することが好ましい。 When the treatment liquid after the thermolysin treatment contains oil, it is preferable to take out a water-soluble fraction further containing a rice bran proteolytic product. Such a water-soluble fraction contains a component that exerts an obesity-improving effect and a type II diabetes-improving effect, which will be described later. The water-soluble fraction can be obtained by, for example, centrifuging the treatment liquid after the thermolysin treatment. Further, it is preferable that the treatment liquid after the thermolysin treatment is collected as a filtrate from which the insoluble fraction has been removed by filtration.

米糠のサーモリシン処理物の使用形態としては、特に限定されず、上記のように得られた処理液を液状の形態で肥満改善用組成物としてそのまま適用してもよく、蒸留等により濃縮した濃縮液として適用してもよく、凍結乾燥等により乾燥させて固形物の形態で適用してもよい。 The form of use of the thermolysin-treated rice bran is not particularly limited, and the treated solution obtained as described above may be applied as it is as a composition for improving obesity in a liquid form, or a concentrated solution concentrated by distillation or the like. It may be applied as a solid substance after being dried by freeze-drying or the like.

米糠のサーモリシン処理物を含む肥満改善用組成物は、肥満改善のために適用され、特に経口摂取により優れた肥満改善作用を発揮する。肥満は、正常な状態と比べて体重が多い状態、体脂肪量が過剰に蓄積した状態を示す。また、本実施形態の肥満改善用組成物は、肥満改善のための適用のみならず、症状の悪化の防止又は遅延、健常者の肥満の予防を目的とした適用も含むものとする。 The obesity-improving composition containing a thermolysin-treated rice bran is applied for obesity-improving, and exhibits an excellent obesity-improving effect particularly when taken orally. Obesity refers to a state in which the body weight is heavier than in a normal state and a state in which the amount of body fat is excessively accumulated. In addition, the composition for improving obesity of the present embodiment includes not only application for improving obesity but also application for prevention or delay of exacerbation of symptoms and prevention of obesity in healthy subjects.

生体において脂肪組織を構成する成熟脂肪細胞は、褐色脂肪細胞と白色脂肪細胞の2つにも大別される。白色脂肪細胞は、脂肪を蓄積する機能を有する脂肪細胞であり、絶食などのエネルギー不足の状態に陥ったときに不足するエネルギーを補う目的で脂肪を分解することが知られている。一方、褐色脂肪細胞は平常状態においても脂肪を酸化分解することが知られている。成人における脂肪細胞の殆どは白色脂肪細胞であり、皮下脂肪や内臓脂肪等として広く分布し、体内の余分なエネルギーを脂肪として蓄積する。本実施形態の肥満改善用組成物は、特に白色脂肪細胞を減少させ、皮下脂肪、内臓脂肪等の過剰な体脂肪を減少させることにより、肥満状態を改善させる。 Mature adipocytes that make up adipose tissue in a living body are roughly classified into brown adipocytes and white adipocytes. White adipocytes are adipocytes having a function of accumulating fat, and are known to decompose fat for the purpose of supplementing the lack of energy when a state of energy shortage such as fasting occurs. On the other hand, brown adipocytes are known to oxidatively decompose fat even in a normal state. Most of the adipocytes in adults are white adipocytes, which are widely distributed as subcutaneous fat, visceral fat, etc., and accumulate excess energy in the body as fat. The composition for improving obesity of the present embodiment improves the obesity state by particularly reducing white adipocytes and reducing excess body fat such as subcutaneous fat and visceral fat.

本実施形態の肥満改善用組成物は、肥満が関連する各種疾患の改善、悪化の防止、予防のために用いられてもよい。肥満改善用組成物の適用により肥満が改善し、肥満が関連する各種疾患の改善効果が期待される。肥満が関連する各種疾患としては、例えば糖尿病、動脈硬化、耐糖能異常、メタボリックシンドローム、高血圧、高脂血症、高中性脂肪血症、高コレステロール血症、肝疾患、歯周病(歯肉炎、歯周炎)等が挙げられる。 The obesity-improving composition of the present embodiment may be used for improving, preventing or preventing various obesity-related diseases. The application of the composition for improving obesity improves obesity and is expected to have an effect of improving various diseases related to obesity. Various diseases related to obesity include, for example, diabetes, arteriosclerosis, abnormal glucose tolerance, metabolic syndrome, hypertension, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, liver disease, periodontal disease (gingeritis, Periodontitis) and the like.

肥満改善用組成物の適用形態としては、特に限定されず、例えば飲食品、医薬品、医薬部外品として適用される。米糠のサーモリシン処理物は、そのまま飲食品又は医薬品素材として用いてもよいし、薬学上又は食品衛生学上許容される担体、添加物等を適宜配合したうえで、製品としてもよい。 The application form of the composition for improving obesity is not particularly limited, and is applied, for example, as a food or drink, a pharmaceutical product, or a quasi-drug. The thermolysin-treated product of rice bran may be used as it is as a food or drink or a pharmaceutical material, or may be used as a product after appropriately blending a carrier, an additive or the like that is acceptable in terms of pharmacy or food hygiene.

本実施形態の肥満改善用組成物を、食品、飲料等の飲食品に適用する場合、例えば食品添加用組成物、各種菓子類、ガム類、錠剤、カプセル(ソフトカプセル、ハードカプセル)、各種加工食品、各種飲料等に適用できる。形態としては、適用する素材に応じて適宜設計することができ、例えば粉末状、顆粒状等の固体状、ペースト状、液状等として構成できる。 When the composition for improving obesity of the present embodiment is applied to foods and drinks such as foods and beverages, for example, food additive compositions, various confectioneries, gums, tablets, capsules (soft capsules, hard capsules), various processed foods, etc. It can be applied to various beverages. The form can be appropriately designed according to the material to be applied, and can be configured as, for example, a solid state such as powder or granule, a paste, or a liquid.

飲食品の用途としては、特に限定されず、いわゆる一般食品、健康食品、機能性食品、栄養補助食品、サプリメント、病者用食品、特定用途食品、保健機能食品、栄養機能食品、特定保健用食品、機能性表示食品等として適用できる。また、さらにはダイエット用食品、美容食品、運動療法時向けの食品及び肥満治療食として適用してもよい。飲食品において用途の表示を付す場合、各種法律、施行規則、ガイドライン等によって定められた表示が挙げられる。飲食品において用途の表示には、包装、容器等のパッケージへの表示の他、パンフレット等の広告媒体への表示も含まれる。本実施形態の肥満改善用組成物の用途の表示内容としては、肥満の改善、予防、悪化の防止、又は症状の遅延の表示の他、上述した肥満が関連する各種疾患の改善、予防、悪化の防止、又は症状の遅延の表示が挙げられる。また、これらの改善、予防、悪化の防止、又は症状の遅延を示唆する表示も含まれる。例えば体脂肪、体脂肪率、血中中性脂肪、皮下脂肪、おなか周りの脂肪、内臓脂肪等の脂肪の低減、減少又は増加の抑制、体重の低減、減少又は増加の抑制、体格指数(BMI)の低下、高めのBMI値の改善、体型の改善、ウエスト周囲径の減少を助ける等の表現が挙げられる。 The uses of foods and drinks are not particularly limited, and are so-called general foods, health foods, functional foods, dietary supplements, supplements, foods for the sick, special-purpose foods, health functional foods, nutritional functional foods, and foods for specified health use. , Applicable as functional foods. Further, it may be applied as a diet food, a beauty food, a food for exercise therapy, and an obesity treatment food. When a label of use is attached to food and drink, the label stipulated by various laws, enforcement regulations, guidelines, etc. can be mentioned. In the case of food and drink, the indication of use includes not only the indication on packages such as packaging and containers, but also the indication on advertising media such as pamphlets. In addition to displaying the improvement, prevention, prevention of exacerbation, or delay of symptoms of obesity, the display contents of the use of the composition for obesity improvement of the present embodiment include improvement, prevention, and exacerbation of various obesity-related diseases described above. Prevention of obesity, or indication of delayed symptoms. It also includes indications suggesting these improvements, preventions, prevention of exacerbations, or delays in symptoms. For example, reduction, suppression of decrease or increase of fat such as body fat, body fat percentage, blood neutral fat, subcutaneous fat, abdominal fat, visceral fat, weight loss, suppression of decrease or increase, body mass index (BMI) ) Decrease, improve BMI value higher, improve body shape, help reduce waist circumference, and so on.

本実施形態の肥満改善用組成物を、医薬品又は医薬部外品として使用する場合は、服用(経口摂取)により投与する場合の他、経腸投与等を採用することが可能である。剤形としては、特に限定されないが、例えば散剤、粉剤、顆粒剤、錠剤、カプセル剤、丸剤、坐剤、液剤等として構成してもよい。また、添加物として賦形剤、基剤、乳化剤、溶剤、安定剤等を配合してもよい。 When the composition for improving obesity of the present embodiment is used as a drug or a quasi-drug, it can be administered by intestinal administration or the like in addition to the case of administration by ingestion (oral ingestion). The dosage form is not particularly limited, but may be configured as, for example, a powder, a powder, a granule, a tablet, a capsule, a pill, a suppository, a liquid, or the like. Further, excipients, bases, emulsifiers, solvents, stabilizers and the like may be blended as additives.

本実施形態の肥満改善用組成物の作用及び効果について説明する。
(1)一般に、正常な状態に比べ体重が多い状況又は体脂肪が過剰に蓄積した状態を肥満という。最近では、肥満は、BMIを指標として定量的に把握することが可能となった。肥満となる原因は、様々であるが、例えば高カロリー食、飲酒・喫煙、運動不足、ストレス等の生活習慣が原因で生ずることが多い。肥満は、心筋梗塞、脳梗塞等の成人病の原因とされる動脈硬化症の危険因子として知られ、社会的に重大な問題となっている。肥満の症状は、食生活の改善、適度な運動以外に根本的な治療法が確立されていないのが現状である。肥満に該当する人は、健常者に比べ、心筋梗塞や脳梗塞を発症するリスクが高いため、現在、肥満の予防用組成物や改善用組成物の開発が急務となっている。
The action and effect of the obesity-improving composition of the present embodiment will be described.
(1) Generally, a state in which the body weight is heavier than in a normal state or a state in which body fat is excessively accumulated is called obesity. Recently, obesity can be quantitatively grasped using BMI as an index. There are various causes of obesity, but it is often caused by lifestyle-related habits such as high-calorie diet, drinking / smoking, lack of exercise, and stress. Obesity is known as a risk factor for arteriosclerosis, which is a cause of adult diseases such as myocardial infarction and cerebral infarction, and has become a serious social problem. At present, no fundamental treatment method has been established for the symptoms of obesity other than improvement of eating habits and moderate exercise. Since people with obesity have a higher risk of developing myocardial infarction and cerebral infarction than healthy people, there is an urgent need to develop a composition for preventing obesity and a composition for improving obesity.

本実施形態の肥満改善用組成物は、米糠のサーモリシン処理物を含むよう構成した。天然由来の成分であるため生体に対して安全に適用することができ、優れた肥満の改善作用を発揮できる。 The composition for improving obesity of the present embodiment was configured to contain a thermolysin-treated product of rice bran. Since it is a naturally derived component, it can be safely applied to the living body and can exert an excellent effect of improving obesity.

(第2実施形態)
以下、本発明のII型糖尿病改善用組成物を具体化した第2実施形態を説明する。以下、第1実施形態との相違点を中心に説明する。本実施形態のII型糖尿病改善用組成物に用いられる米糠のサーモリシン処理物は、第1実施形態と同様である。
(Second Embodiment)
Hereinafter, a second embodiment in which the composition for improving type II diabetes of the present invention is embodied will be described. Hereinafter, the differences from the first embodiment will be mainly described. The thermolysin-treated rice bran used in the composition for improving type II diabetes of the present embodiment is the same as that of the first embodiment.

本実施形態のII型糖尿病改善用組成物は、II型糖尿病改善のために適用され、特に経口摂取により優れたII型糖尿病改善作用を発揮する。特に糖代謝の改善又はインスリン抵抗性の改善により、II型糖尿病の症状を改善させる。II型糖尿病は、血糖値及びヘモグロビンA1c値が所定の基準を超えている状態を示す疾患であるが、本実施形態においては血糖値及びヘモグロビンA1c値が平常値よりも高い状態の者、例えばいわゆる糖尿病予備群も含まれるものとする。糖代謝の改善とは、例えば血糖値及びヘモグロビンA1c(HA1c)値の改善を示す。また、本実施形態のII型糖尿病改善用組成物は、II型糖尿病改善に関する症状の改善を目的とした患者への適用のみならず、症状の悪化の防止又は遅延、健常者のII型糖尿病の予防を目的とした適用も含むものとする。 The composition for improving type II diabetes of the present embodiment is applied for improving type II diabetes, and exhibits an excellent type II diabetes improving effect particularly when taken orally. In particular, it improves the symptoms of type II diabetes by improving glucose metabolism or insulin resistance. Type II diabetes is a disease in which the blood glucose level and the hemoglobin A1c level exceed a predetermined standard, but in the present embodiment, the blood glucose level and the hemoglobin A1c level are higher than the normal values, for example, so-called. The diabetic reserve group shall also be included. Improvement of glucose metabolism means, for example, improvement of blood glucose level and hemoglobin A1c (HA1c) level. In addition, the composition for improving type II diabetes of the present embodiment is not only applied to patients for the purpose of improving symptoms related to improvement of type II diabetes, but also prevents or delays exacerbation of symptoms, and causes type II diabetes in healthy subjects. It shall also include application for the purpose of prevention.

本実施形態のII型糖尿病改善用組成物は、II型糖尿病が関連する糖尿病の各種合併症の改善、悪化の防止、予防のために用いられてもよい。II型糖尿病改善用組成物の適用により糖尿病が改善し、合併症の改善効果が期待される。糖尿病の合併症としては、例えば糖尿病性神経障害、糖尿病性網膜症、糖尿病性腎症等が挙げられる。 The composition for improving type II diabetes of the present embodiment may be used for improving, preventing or preventing various complications of diabetes associated with type II diabetes. The application of the composition for improving type II diabetes improves diabetes and is expected to have an effect of improving complications. Examples of diabetic complications include diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy.

II型糖尿病改善用組成物の適用形態としては、第1実施形態と同様である。なお、飲食品に適用される場合、II型糖尿病改善用組成物の用途の表示内容としては、II型糖尿病の改善、予防、悪化の防止、又は症状の遅延の表示の他、上述した合併症の改善、予防、悪化の防止、又は症状の遅延の表示が挙げられる。また、これらの改善、予防、悪化の防止、又は症状の遅延を示唆する表示も含まれる。例えば血糖値又はHA1c値の改善、悪化の防止、食後の血糖値の上昇が緩やか、血糖値が気になる方等の表現が挙げられる。 The application form of the composition for improving type II diabetes is the same as that of the first embodiment. When applied to foods and drinks, the indications for the use of the composition for improving type II diabetes include the indication of improvement, prevention, prevention of exacerbation of type II diabetes, or delay of symptoms, as well as the above-mentioned complications. Improvement, prevention, prevention of exacerbation, or indication of delayed symptoms. It also includes indications suggesting these improvements, preventions, prevention of exacerbations, or delays in symptoms. For example, there are expressions such as improvement of blood glucose level or HA1c level, prevention of deterioration, gradual rise of blood glucose level after meal, and those who are concerned about blood glucose level.

本実施形態のII型糖尿病改善用組成物の作用及び効果について説明する。
(2)本実施形態のII型糖尿病改善用組成物は、米糠のサーモリシン処理物を含むよう構成した。天然由来の成分であるため生体に対して安全に適用することができ、優れたII型糖尿病の改善作用を発揮できる。
The action and effect of the type II diabetes improving composition of the present embodiment will be described.
(2) The composition for improving type II diabetes of the present embodiment was configured to contain a thermolysin-treated product of rice bran. Since it is a naturally derived component, it can be safely applied to a living body and can exert an excellent effect of improving type II diabetes.

尚、上記実施形態は、以下のように変更して実施できる。上記実施形態及び以下の変更例は、技術的に矛盾しない範囲で互いに組み合わせて実施できる。
・上記実施形態の肥満改善用組成物又はII型糖尿病改善用組成物は、ヒト以外の飼養動物に適用してもよい。
The above embodiment can be modified as follows. The above embodiment and the following modified examples can be implemented in combination with each other within a technically consistent range.
-The composition for improving obesity or the composition for improving type II diabetes of the above-described embodiment may be applied to domestic animals other than humans.

・上記実施形態の肥満改善用組成物又はII型糖尿病改善用組成物において、医薬品、医薬部外品、又は飲食品に含まれる米糠のサーモリシン処理物の量は、本発明の効果が得られる限り特に制限されず、固形分中において例えば0.1〜100質量%、好ましくは1〜90質量%含むよう構成できる。また、一日の摂取量、摂取期間も目的・容態等に応じて適宜設定できる。 -In the composition for improving obesity or the composition for improving type II diabetes of the above-described embodiment, the amount of the thermolysin-treated rice bran contained in the drug, quasi-drug, or food or drink is as long as the effect of the present invention can be obtained. It is not particularly limited, and can be configured to contain, for example, 0.1 to 100% by mass, preferably 1 to 90% by mass in the solid content. In addition, the daily intake and the intake period can be appropriately set according to the purpose, condition, and the like.

・上記実施形態の肥満改善用組成物又はII型糖尿病改善用組成物に配合した米糠のサーモリシン処理物中において、圧搾脱脂米糠を原料して調製した場合、米糠原料中の油性成分であるγ−オリザノールは、例えば50mg/100g(固形分)以下、好ましくは25mg/100g(固形分)以下に調製されてもよい。 -When prepared using pressed defatted rice bran as a raw material in the thermolysin-treated rice bran blended in the composition for improving obesity or the composition for improving type II diabetes of the above embodiment, γ-, which is an oily component in the rice bran raw material, is used. Oryzanol may be prepared, for example, in an amount of 50 mg / 100 g (solid content) or less, preferably 25 mg / 100 g (solid content) or less.

以下に試験例を挙げ、前記実施形態をさらに具体的に説明するが、本発明はこれらに限定されるものではない。
<試験例1:肥満改善及びII型糖尿病改善の各作用について>
(米糠のサーモリシン処理物の調製)
原料米糠としては、サンブラン社製の商品名ハイブレフを用いた。ハイブレフは、米糠を圧搾することより脱脂を行った圧搾脱脂米糠である。また、サーモリシンは、ペプチド研究所社製のもの(Code3504)を用いた。
Hereinafter, the above-described embodiment will be described in more detail with reference to test examples, but the present invention is not limited thereto.
<Test Example 1: Improvement of obesity and type II diabetes>
(Preparation of thermolysin-treated rice bran)
As the raw material rice bran, the trade name Hibref manufactured by Saint-Blanc was used. Hybref is a squeezed degreased rice bran that has been degreased by squeezing the rice bran. As the thermolysin, one manufactured by Peptide Institute (Code3504) was used.

まず、超純水に米糠原料を30g/Lとなるように混合し、これにサーモリシンを0.4g/Lとなるように加えた。そして、当該混合物を37℃インキュベータ内でスターラーを用いて250r.p.m.で攪拌しながら20時間インキュベートしながら酵素処理した。次に、沸騰水浴に浸漬して15分間処理し、酵素を失活させた。その後、15℃、7150r.p.m.(8000×g)で15分遠心分離処理を行い、固液分離を行った。得られた上清のpHをNaOHを用いて7.0に調整し、フィルターペーパーNo.2(アドバンテック社製)を用いて濾過して、得られた濾液を凍結乾燥した。当該凍結乾燥物を、米糠サーモリシン処理物として使用した。なお、米糠サーモリシン処理物中には、限外濾過により約10kDa以下のペプチドが含まれていることを確認している。また、アミノ酸配列分析により、配列番号1及びLeu−Arg−Alaのペプチドが含まれていることを確認している。 First, the rice bran raw material was mixed with ultrapure water so as to be 30 g / L, and thermolysin was added to this so as to be 0.4 g / L. Then, the mixture was enzymatically treated in a 37 ° C. incubator using a stirrer while stirring at 250 r.p.m. for 20 hours. Next, it was immersed in a boiling water bath and treated for 15 minutes to inactivate the enzyme. Then, the mixture was centrifuged at 7150 r.p.m. (8000 × g) for 15 minutes at 15 ° C. to perform solid-liquid separation. The pH of the obtained supernatant was adjusted to 7.0 using NaOH, and the filter paper No. Filtration was carried out using 2 (manufactured by Advantech), and the obtained filtrate was lyophilized. The freeze-dried product was used as a rice bran thermolysin-treated product. It has been confirmed by ultrafiltration that the rice bran thermolysin-treated product contains a peptide of about 10 kDa or less. In addition, it has been confirmed by amino acid sequence analysis that the peptides of SEQ ID NO: 1 and Leu-Arg-Ala are contained.

(マウス及び飼料)
マウスを用いてin vivo試験を行った。マウスはII型糖尿病自然発症マウスであるNSYマウス(星野試験動物飼育所社製)を用いた。NSYマウスは、軽度の肥満、内臓脂肪の蓄積、インスリン抵抗性を特徴としている。
(Mouse and feed)
An in vivo test was performed using mice. As the mouse, NSY mouse (manufactured by Hoshino Test Animal Breeding Co., Ltd.), which is a spontaneous type II diabetic mouse, was used. NSY mice are characterized by mild obesity, visceral fat accumulation, and insulin resistance.

試験食は、高脂肪食として下記表1に示される成分からなるHFD-60(オリエンタル酵母社製)を使用した。米糠サーモリシン処理物配合の高脂肪食は、表1に示されるようにHFD-60の組成をベースとして上記米糠サーモリシン処理物を0.04質量%配合した高脂肪食を調製した。 As a test diet, HFD-60 (manufactured by Oriental Yeast Co., Ltd.) consisting of the components shown in Table 1 below was used as a high-fat diet. As the high-fat diet containing the rice bran thermolysin-treated product, a high-fat diet containing 0.04% by mass of the above-mentioned rice bran thermolysin-treated product was prepared based on the composition of HFD-60 as shown in Table 1.

なお、高脂肪食に配合した米糠サーモリシン処理物、及び原料米糠として使用した圧搾脱脂米糠(ハイブレフ)のそれぞれについて、γ−オリザノールの含有量をHPLCを用いて測定した。結果を表2に示す。 The content of γ-oryzanol was measured by HPLC for each of the rice bran thermolysin-treated product blended in the high-fat diet and the pressed defatted rice bran (Hybref) used as the raw material rice bran. The results are shown in Table 2.

Figure 2021093995
Figure 2021093995

Figure 2021093995
(飼育条件及び飼料の投与)
まず、通常食(CE-2固形)にて予備飼育後、4週齢となったマウスに高脂肪食(HFD-60)のみを3週間与えた。7週齢となったマウスの体重を測定し、各群の体重の平均値の有意差がなくなるように、高脂肪食のみで飼育するコントロール群(n=8)と、米糠サーモリシン処理物配合の高脂肪食を与える実施例群(n=8)の2群に分けた。その後、コントロール群は、26週齢まで高脂肪食のみを与えた。一方、実施例群においては、7週齢から26週齢まで米糠サーモリシン処理物配合の高脂肪食を与えた。尚、飼育中は自由摂食・自由引飲水とし、飼育環境は12時間明期/12時間暗期であった。飼育期間中は1週間ごとに体重を測定し、餌補充時に適宜摂餌量も測定した。また、後述する糖負荷試験においては、別途個体群を用意し、糖負荷試験欄に記載される週齢のマウスを同様の方法にて飼育した。
Figure 2021093995
(Breeding conditions and feed administration)
First, after pre-rearing on a normal diet (CE-2 solid), mice aged 4 weeks were fed only a high-fat diet (HFD-60) for 3 weeks. Weigh the 7-week-old mice and mix them with a control group (n = 8) that is bred only on a high-fat diet and a rice bran thermolysin-treated product so that there is no significant difference in the average body weight of each group. It was divided into two groups, an example group (n = 8) on which a high-fat diet was given. The control group was then fed only a high-fat diet until 26 weeks of age. On the other hand, in the example group, a high-fat diet containing a rice bran thermolysin-treated product was fed from 7 to 26 weeks of age. During breeding, free feeding and free drinking were used, and the breeding environment was 12 hours light period / 12 hours dark period. During the breeding period, the body weight was measured weekly, and the amount of food intake was also measured as appropriate when supplementing food. Further, in the glucose tolerance test described later, a separate population was prepared, and the week-aged mice described in the glucose tolerance test column were bred by the same method.

各試験群において7〜25週齢まで体重変化を測定した。各試験グループの個体群において平均値±標準誤差を求めた。結果を図1に示す。なお、図中の*は、p<0.05、§はp<0.1(t検定)を示す。 Body weight changes were measured from 7 to 25 weeks of age in each test group. Mean ± standard error was calculated for the population of each test group. The results are shown in FIG. In the figure, * indicates p <0.05, and § indicates p <0.1 (t test).

また、各試験群において7〜25週齢まで試験食の摂取量(g/日)の平均値を求めた。各試験グループの個体群において平均値±標準誤差を求めた。結果を図2に示す。
(糖負荷試験)
糖負荷試験をipGTT法により行った。まず、8〜12週齢経過した各個体群のマウス(n=10−11)を1晩(15時間)絶食後、動物の尾を穿刺し、簡易血糖値測定装置を用いて血糖値を測定した(空腹時血糖値)。空腹時血糖値を測定した後、2g/kg B.Wのグルコースを腹腔内投与した。グルコース腹腔内投与後の所定時間毎に、空腹時血糖値測定と同様に尾を穿刺し、簡易血糖値測定装置を用いて血糖値を測定した。各試験グループの個体群において血糖値の平均値±標準誤差を求めた。結果を図3に示す。なお、図中の*は、p<0.05(t検定)を示す。
In addition, the average value of the intake (g / day) of the test meal was calculated from 7 to 25 weeks of age in each test group. Mean ± standard error was calculated for the population of each test group. The results are shown in FIG.
(Glucose tolerance test)
The glucose tolerance test was performed by the ipGTT method. First, after fasting overnight (15 hours) of mice (n = 10-11) of each population aged 8 to 12 weeks, the tail of the animal is punctured and the blood glucose level is measured using a simple blood glucose level measuring device. (Fasting blood glucose level). After measuring the fasting blood glucose level, 2 g / kg BW glucose was intraperitoneally administered. At predetermined time intervals after intraperitoneal administration of glucose, the tail was punctured in the same manner as in the fasting blood glucose level measurement, and the blood glucose level was measured using a simple blood glucose level measuring device. The mean ± standard error of blood glucose level was calculated in the population of each test group. The results are shown in FIG. Note that * in the figure indicates p <0.05 (t-test).

(インスリン負荷試験)
インスリン負荷試験をITT法により行った。まず、26週齢経過した各個体群(n=6−7)のマウスを1晩(15時間)絶食後、動物の尾を穿刺し、簡易血糖値測定装置を用いて血糖値を測定した(空腹時血糖値)。空腹時血糖値を測定した後、0.5 U/kgインスリンを腹腔内投与した。インスリン腹腔内投与後の所定時間毎に、空腹時血糖値測定と同様に尾を穿刺し、簡易血糖値測定装置を用いて血糖値を測定した。各試験グループの個体群において測定開始時の血糖値を100とした場合、血糖値レベルの平均値±標準誤差を求めた。結果を図4に示す。なお、図中の*は、p<0.05(t検定)を示す。
(Insulin tolerance test)
The insulin tolerance test was performed by the ITT method. First, mice of each population (n = 6-7) 26 weeks old were fasted overnight (15 hours), the tails of the animals were punctured, and the blood glucose level was measured using a simple blood glucose level measuring device (a simple blood glucose level measuring device). Fasting blood glucose level). After measuring the fasting blood glucose level, 0.5 U / kg insulin was intraperitoneally administered. At predetermined time intervals after intraperitoneal administration of insulin, the tail was punctured in the same manner as in the fasting blood glucose level measurement, and the blood glucose level was measured using a simple blood glucose level measuring device. Assuming that the blood glucose level at the start of measurement was 100 in the population of each test group, the average value ± standard error of the blood glucose level was calculated. The results are shown in FIG. Note that * in the figure indicates p <0.05 (t-test).

(脂肪組織等の質量測定)
上記試験終了後、セボフレンによる麻酔環境下で眼底採血後、肝臓、白色脂肪組織、及び褐色脂肪組織をそれぞれ摘出し、重さ(g)を測定した。各試験グループの個体群において平均値±標準誤差を求めた。コントロール群及び実施例群の肝臓、白色脂肪組織、及び褐色脂肪組織の重さを図5〜7にそれぞれ示す。図中の*は、p<0.05(t検定)を示す。
(Mass measurement of adipose tissue, etc.)
After completion of the above test, blood was collected from the fundus under anesthesia with sevofluene, and then the liver, white adipose tissue, and brown adipose tissue were excised and weighed (g). Mean ± standard error was calculated for the population of each test group. The weights of the liver, white adipose tissue, and brown adipose tissue of the control group and the example group are shown in FIGS. 5 to 7, respectively. * In the figure indicates p <0.05 (t-test).

(結果)
図1に示されるように、各週齢において体重上昇の割合がコントロール群に比べて米糠サーモリシン処理物を高脂肪食に添加した実施例群において有意に抑制されたことが認められた。
(result)
As shown in FIG. 1, it was found that the rate of body weight gain at each week was significantly suppressed in the example group in which the rice bran thermolysin-treated product was added to the high-fat diet as compared with the control group.

図5に示されるように、白色脂肪組織の質量がコントロール群に比べて米糠サーモリシン処理物を高脂肪食に添加した実施例群において有意に低下したことが認められた。
つまり、米糠サーモリシン処理物の摂取により、肥満改善作用が認められた。なお、図2に示されるようにコントロール群と実施例群では、試験食の摂取量に違いは見られなかった。
As shown in FIG. 5, it was found that the mass of white adipose tissue was significantly reduced in the example group in which the rice bran thermolysin-treated product was added to the high-fat diet as compared with the control group.
In other words, ingestion of the rice bran thermolysin-treated product was found to have an obesity-improving effect. As shown in FIG. 2, there was no difference in the intake of the test meal between the control group and the example group.

図3に示されるように、糖負荷試験において、コントロール群に比べて米糠サーモリシン処理物を高脂肪食に添加した実施例群において血糖値の上昇が有意に抑制されたことが認められた。 As shown in FIG. 3, in the glucose tolerance test, it was found that the increase in blood glucose level was significantly suppressed in the example group in which the rice bran thermolysin-treated product was added to the high-fat diet as compared with the control group.

図4に示されるように、インスリン負荷試験において、コントロール群のように0.5U/kgと強くインスリン負荷をしても血糖値の低下がみられないのに対し、米糠サーモリシン処理物を高脂肪食に添加した実施例群では血糖値が有意に低下した。米糠サーモリシン処理物には、肥満改善作用の他に、糖代謝の改善及びインスリン抵抗性の改善作用によるII型糖尿病改善作用も認められた。 As shown in FIG. 4, in the insulin tolerance test, the blood glucose level did not decrease even when the insulin load was as strong as 0.5 U / kg as in the control group, whereas the rice bran thermolysin-treated product was high in fat. The blood glucose level was significantly reduced in the example group added to the diet. In addition to the obesity-improving effect, the rice bran thermolysin-treated product was also found to have a type II diabetes-improving effect by improving glucose metabolism and insulin resistance.

なお、表2に示されるように、米糠サーモリシン処理物は、圧搾脱脂米糠と比べてγ−オリザノールの含有量が著しく少ないため、肥満改善作用及びII型糖尿病改善作用は、脂溶性以外の成分の関与が示唆された。 As shown in Table 2, the rice bran thermolysin-treated product has a significantly lower content of γ-oryzanol than the pressed defatted rice bran, so that the obesity-improving action and the type II diabetes-improving action are components other than fat-soluble components. Involvement was suggested.

<処方例>
以下に、米糠サーモリシン処理物を用いた処方例を示す。
(処方例1:錠剤)
米糠サーモリシン処理物:10質量%
賦形剤(結晶セルロース等):90質量%
(合計100質量%)
(処方例2:飲料)
米糠サーモリシン処理物:10質量%
果汁:30質量%
水:60質量%
(合計100質量%)
<Prescription example>
An example of prescription using a rice bran thermolysin-treated product is shown below.
(Prescription example 1: Tablet)
Rice bran thermolysin treated product: 10% by mass
Excipients (crystalline cellulose, etc.): 90% by mass
(100% by mass in total)
(Prescription example 2: Beverage)
Rice bran thermolysin treated product: 10% by mass
Juice: 30% by mass
Water: 60% by mass
(100% by mass in total)

Claims (6)

米糠のサーモリシン処理物を含む肥満改善用組成物。 A composition for improving obesity containing a thermolysin-treated product of rice bran. 前記サーモリシン処理物は、配列番号1及びLeu−Arg−Alaから選ばれる少なくとも一種を含む請求項1に記載の肥満改善用組成物。 The composition for improving obesity according to claim 1, wherein the thermolysin-treated product contains at least one selected from SEQ ID NO: 1 and Leu-Arg-Ala. 前記サーモリシン処理物は、圧搾脱脂米糠をサーモリシン処理したものであって、水溶性画分である請求項1又は2に記載の肥満改善用組成物。 The composition for improving obesity according to claim 1 or 2, wherein the thermolysin-treated product is a thermolysin-treated pressed degreased rice bran and is a water-soluble fraction. 前記肥満改善は、白色脂肪組織の減少である請求項1〜3のいずれか一項に記載の肥満改善用組成物。 The composition for improving obesity according to any one of claims 1 to 3, wherein the improvement in obesity is a reduction in white adipose tissue. 米糠のサーモリシン処理物を含むII型糖尿病改善用組成物。 A composition for improving type II diabetes, which comprises a thermolysin-treated product of rice bran. 前記II型糖尿病改善は、糖代謝の改善又はインスリン抵抗性の改善である請求項5に記載のII型糖尿病改善用組成物。 The composition for improving type II diabetes according to claim 5, wherein the improvement of type II diabetes is an improvement of glucose metabolism or an improvement of insulin resistance.
JP2019229206A 2019-12-19 2019-12-19 Composition for ameliorating obesity and composition for ameliorating type ii diabetes Pending JP2021093995A (en)

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