JP5925569B2 - Gastrointestinal hormone secretion regulator - Google Patents
Gastrointestinal hormone secretion regulator Download PDFInfo
- Publication number
- JP5925569B2 JP5925569B2 JP2012091175A JP2012091175A JP5925569B2 JP 5925569 B2 JP5925569 B2 JP 5925569B2 JP 2012091175 A JP2012091175 A JP 2012091175A JP 2012091175 A JP2012091175 A JP 2012091175A JP 5925569 B2 JP5925569 B2 JP 5925569B2
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- JP
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- Prior art keywords
- alginic acid
- molecular weight
- average molecular
- secretion
- salt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Description
本発明は、消化管ホルモン分泌調節剤に関する。 The present invention relates to a gastrointestinal hormone secretion regulator.
消化管ホルモンは、消化管粘膜内に散在する特定の内分泌細胞から産生され、消化管、肝、胆、膵等へ作用してその分泌と運動を調節することが知られているホルモンである。 Gastrointestinal hormones are hormones that are produced from specific endocrine cells scattered within the gastrointestinal mucosa and are known to act on the gastrointestinal tract, liver, bile, pancreas, etc. to regulate their secretion and movement.
Ｇｌｕｃａｇｏｎ−ｌｉｋｅ ｐｅｐｔｉｄｅ−１（ＧＬＰ−１）は、インクレチン（ｉｎｃｒｅｔｉｎ： Ｉｎｔｅｓｔｉｎｅ Ｓｅｃｒｅｔｉｏｎ Ｉｎｓｕｌｉｎ）作用を備えたホルモンであり、膵β細胞からのインスリン分泌を促進させ、あるいは膵臓からのグルカゴン分泌を抑制することにより、血糖値を低下させる。ＧＬＰ−１による血糖値低下作用は、低血糖によるグルカゴン分泌と拮抗せず、またインスリン濃度に依存しないことが報告されていることから、糖尿病患者の血糖値制御に有用である。ＧＬＰ−１投与により１型糖尿病患者及び２型糖尿病患者で共にインスリン量が減少したことが報告されている（非特許文献１）。
他のＧＬＰ−１の作用としては、膵β細胞の増殖促進、胃排泄や胃酸分泌の抑制、食欲と摂食の抑制等が知られている（非特許文献２）。また、中枢神経系を介した記憶学習能力向上作用や、神経突起伸長促進作用、神経傷害によるアポトーシスからの保護作用があることが知られており（非特許文献３〜４）、認知症等の神経変性疾患や糖尿病に伴う神経障害の改善に有用であると考えられている。
従って、ＧＬＰ−１の効果を高めることは、肥満、糖尿病等の生活習慣病の改善に有用である。近年では、ＧＬＰ−１補充療法やＧＬＰ−１受容体（ＧＬＰ−１Ｒ）アゴニストを利用した糖尿病治療法の開発も進められている。しかし、通常ＧＬＰ−１は非常に分解され易く、生体内での半減期は非常に短いため、体外からＧＬＰ−１を投与しても、その血中濃度を一定に保つのは非常に難しい。従って、生体内でのＧＬＰ−１濃度を長時間にわたって高めるためには、外からの投与よりも内因性ＧＬＰ−１の分泌を促進することが望ましい。
Glucagon-like peptide-1 (GLP-1) is a hormone having an incretin (Incretin Secretion Insulin) action, and promotes insulin secretion from pancreatic β cells or suppresses glucagon secretion from the pancreas. As a result, the blood sugar level is lowered. It has been reported that the blood glucose level-lowering effect by GLP-1 does not antagonize glucagon secretion due to hypoglycemia and does not depend on the insulin concentration, and thus is useful for blood glucose level control in diabetic patients. It has been reported that the amount of insulin decreased in both type 1 diabetic patients and type 2 diabetic patients by GLP-1 administration (Non-patent Document 1).
Other actions of GLP-1 are known to promote proliferation of pancreatic β cells, suppress gastric excretion and gastric acid secretion, suppress appetite and food intake, etc. (Non-patent Document 2). In addition, it is known that there is an action to improve memory learning ability through the central nervous system, an action to promote neurite outgrowth, and a protective action from apoptosis due to nerve injury (Non-Patent Documents 3 to 4). It is considered useful for improving neuropathy associated with neurodegenerative diseases and diabetes.
Therefore, enhancing the effect of GLP-1 is useful for improving lifestyle-related diseases such as obesity and diabetes. In recent years, development of diabetes treatment methods using GLP-1 replacement therapy and GLP-1 receptor (GLP-1R) agonists has also been promoted. However, since GLP-1 is usually very easily degraded and has a very short half-life in vivo, it is very difficult to keep the blood concentration constant even if GLP-1 is administered from outside the body. Therefore, in order to increase the in vivo GLP-1 concentration over a long period of time, it is desirable to promote the secretion of endogenous GLP-1 rather than external administration.
Ｇａｓｔｒｉｃ ｉｎｈｉｂｉｔｏｒｙ ｐｏｌｙｐｅｐｔｉｄｅ（ＧＩＰ）は、胃酸分泌抑制作用や胃運動抑制作用を有することが知られている。また、ＧＩＰは、膵β細胞からのインスリン分泌を促進し、インスリン存在下でのグルコースの脂肪細胞への取り込みを亢進することが知られている。そのため、ＧＩＰの作用が肥満の一要因になっているとも考えられ、事実、ＧＩＰの機能を阻害すると、肥満が抑制されるとの報告がある（非特許文献５）。そのため、ＧＩＰの上昇抑制は、食後の消化促進や胃もたれの改善、又は肥満の予防・改善等に有効であると考えられる。 Gastroinhibitory polypeptide (GIP) is known to have a gastric acid secretion inhibitory action and a gastric movement inhibitory action. In addition, GIP is known to promote insulin secretion from pancreatic β cells and enhance glucose uptake into adipocytes in the presence of insulin. For this reason, it is considered that the action of GIP is a factor in obesity. In fact, there is a report that obesity is suppressed when the function of GIP is inhibited (Non-patent Document 5). Therefore, it is considered that the suppression of the increase in GIP is effective for promoting digestion after meals, improving stomach sag, or preventing or improving obesity.
ペプチドＹＹ（ＰＹＹ）は１９６８年にブタの小腸より単離されたペプチドで、ニューロペプチドＹ（ＮＰＹ）、膵ポリペプチド（ＰＰ）とともに一つのペプチドファミリーを形成している。ＰＹＹは、主に下部消化管（回腸および結腸）の粘膜層内細胞から食後分泌される。ＰＹＹの末梢投与は膵外分泌および腸運動を抑制させることが知られている。 Peptide YY (PYY) is a peptide isolated from the small intestine of pigs in 1968, and forms one peptide family together with neuropeptide Y (NPY) and pancreatic polypeptide (PP). PYY is secreted postprandially from cells in the mucosal layer of the lower gastrointestinal tract (ileum and colon). Peripheral administration of PYY is known to suppress exocrine pancreas and intestinal motility.
これまでの研究では、ＧＬＰ−１の分泌を促進する物質として、パルミチン酸、オレイン酸、肉加水分解物（ＭＨ）、ガストリン放出ペプチド（ＧＲＰ）、カルバコール、フォルスコリン、イオノマイシン、酢酸ミリスチン酸ホルボール（ＰＭＡ）、必須アミノ酸（ＥＡＡ）、ロイシン、イソロイシン、スキムミルク、カゼイン、レプチン、ムスカリン性受容体Ｍ１、Ｍ２が報告されている。
また、ＧＩＰの機能を阻害する物質として、３−ブロモ−５−メチル−２−フェニルピラゾロ［１，５−ａ］ピリミジンー７−オール（ＢＭＰＰ）が知られ、食後ＧＩＰの分泌を抑制するものとして、グアガム等が知られている。
また、ＰＹＹの分泌を促進するものとして、レジスタントスターチ、ラクチトール及びβ−グルカンが知られている。
In previous studies, as substances that promote the secretion of GLP-1, palmitic acid, oleic acid, meat hydrolyzate (MH), gastrin releasing peptide (GRP), carbachol, forskolin, ionomycin, phorbol myristate acetate ( PMA), essential amino acids (EAA), leucine, isoleucine, skim milk, casein, leptin, and muscarinic receptors M1 and M2 have been reported.
Further, as a substance that inhibits the function of GIP, 3-bromo-5-methyl-2-phenylpyrazolo [1,5-a] pyrimidin-7-ol (BMPP) is known, which suppresses postprandial GIP secretion As such, guar gum and the like are known.
Moreover, resistant starch, lactitol, and β-glucan are known as those that promote the secretion of PYY.
また特許出願人は、これまでに、平均分子量２０万以下、好ましくは１０万以下のアルギン酸やその塩にＧＩＰ分泌抑制作用があることを見出し、特許出願している（特許文献１）。さらに特許出願人は、平均分子量１〜６万のアルギン酸カリウムにＧＩＰ分泌抑制作用（特許文献２）及び肥満予防改善作用（特許文献３）があること、ならびに平均分子量１〜１０万のアルギン酸又はその塩にペプチドＹＹ分泌促進作用があること（特許文献４）を見出し、特許出願している。
しかし、これらのアルギン酸又はその塩は、いずれも平均分子量２０万以下、特に１０万以下という比較的低分子量のものであった。さらに、特許出願２〜４では、平均分子量が２０万超アルギン酸又はその塩は、粘度が高いため、喉ごし、嚥下のしやすさ等の観点から好ましくないものとされていた。
In addition, the patent applicant has found that alginic acid having an average molecular weight of 200,000 or less, preferably 100,000 or less and a salt thereof have a GIP secretion inhibitory action, and has applied for a patent (Patent Document 1). Furthermore, the patent applicants stated that potassium alginate having an average molecular weight of 1 to 60,000 has a GIP secretion inhibitory action (Patent Document 2) and an obesity prevention improving action (Patent Document 3), and that an alginic acid having an average molecular weight of 1 to 100,000 or its It has been found that a salt has a peptide YY secretion promoting action (Patent Document 4), and has applied for a patent.
However, all of these alginic acids or salts thereof have a relatively low molecular weight of an average molecular weight of 200,000 or less, particularly 100,000 or less. Further, in patent applications 2 to 4, alginic acid having an average molecular weight of more than 200,000 or a salt thereof is considered to be unfavorable from the viewpoints of throat swallowing and ease of swallowing because of its high viscosity.
他方、平均分子量が２０万超のアルギン酸又はその塩は、食品の増粘剤や歯科印象剤のゲル化剤として広く使用されている。例えば、特許文献５及び６には、タンパク質とｐＨ２から４の間で変性または加水分解しないバイオポリマー増粘剤とを配合し、胃内でゲルを形成して胃の膨張を導くことで促進された満腹効果を有する食品組成物が開示され、バイオポリマー増粘剤として好ましい分子量範囲が２０万〜４０万のアルギン酸塩が例示されている。しかし、これらの平均分子量が２０万超のアルギン酸又はその塩については、消化管ホルモン分泌調節を有することは知られていなかった。 On the other hand, alginic acid having an average molecular weight exceeding 200,000 or a salt thereof is widely used as a thickener for foods or a gelling agent for dental impression agents. For example, Patent Documents 5 and 6 are promoted by blending a protein and a biopolymer thickener that is not denatured or hydrolyzed between pH 2 and 4, and forming a gel in the stomach to induce gastric swelling. A food composition having a satiety effect is disclosed, and alginate having a molecular weight range of 200,000 to 400,000 as a biopolymer thickener is exemplified. However, it has not been known that alginic acid or a salt thereof having an average molecular weight exceeding 200,000 has gastrointestinal hormone secretion regulation.
本発明は、医薬又は食品として有用な消化管ホルモン分泌調節剤を提供することに関する。 The present invention relates to providing a gastrointestinal hormone secretion regulator useful as a medicine or food.
本発明者らは、アルギン酸又はその塩の消化管ホルモン分泌に対する作用について詳細に検討し、平均分子量２０万超〜９０万のアルギン酸又はその塩が、ＧＩＰ分泌抑制及びＰＹＹ分泌促進作用を有するとともに、ＧＬＰ−１分泌促進作用を更に有しており、消化管ホルモン分泌調節に優れた作用を発揮し得ることを見出した。 The present inventors examined in detail the action of alginic acid or a salt thereof on gastrointestinal hormone secretion, and alginic acid or a salt thereof having an average molecular weight of more than 200,000 to 900,000 has GIP secretion suppression and PYY secretion promoting action, It has been found that it further has a GLP-1 secretion promoting action and can exhibit an excellent action in regulating gastrointestinal hormone secretion.
すなわち、本発明は以下を提供する。
（１）重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩を有効成分とする消化管ホルモン分泌調節剤。
（２）消化管ホルモン分泌調節が食後ＧＬＰ−１分泌促進である、（１）の調節剤。
（３）消化管ホルモン分泌調節が食後ＧＩＰ分泌抑制である、（１）の調節剤。
（４）消化管ホルモン分泌調節が食後ペプチドＹＹ分泌促進である、（１）の調節剤。
（５）重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩を有効成分とする肥満予防及び／又は改善剤。
（６）重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩を有効成分とする内臓脂肪蓄積抑制剤。
（７）重量平均分子量が２５万以上５０万以下である（１）〜（６）のいずれか１に記載の剤。
（８）アルギン酸の塩がアルギン酸カリウムである（１）〜（７）のいずれか１項に記載の剤。
That is, the present invention provides the following.
(1) A gastrointestinal hormone secretion regulator comprising alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof as an active ingredient.
(2) The regulator of (1), wherein the regulation of gastrointestinal hormone secretion is promotion of postprandial GLP-1 secretion.
(3) The regulator of (1), wherein the regulation of gastrointestinal hormone secretion is suppression of postprandial GIP secretion.
(4) The regulator of (1), wherein the regulation of gastrointestinal hormone secretion is promotion of postprandial peptide YY secretion.
(5) An obesity preventive and / or ameliorating agent comprising alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof as an active ingredient.
(6) A visceral fat accumulation inhibitor containing alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof as an active ingredient.
(7) The agent according to any one of (1) to (6), wherein the weight average molecular weight is from 250,000 to 500,000.
(8) The agent according to any one of (1) to (7), wherein the salt of alginic acid is potassium alginate.
本発明の消化管ホルモン分泌調節剤は、食後におけるＧＬＰ−１、ＧＩＰ、及びペプチドＹＹの分泌を調節することができ、また内臓脂肪蓄積抑制や肥満予防及び／又は改善に有用である。 The gastrointestinal hormone secretion regulator of the present invention can regulate secretion of GLP-1, GIP, and peptide YY after meals, and is useful for suppressing visceral fat accumulation and preventing and / or improving obesity.
本明細書において、「ＧＬＰ−１分泌促進」とは食事を摂取することで引き起こされる生体内でのＧＬＰ−１分泌を促進することを意味する。あるいは、「ＧＬＰ−１分泌促進」とは、主として食後に生じる生体内でのＧＬＰ−１分泌に伴う血中ＧＬＰ−１濃度上昇を増強するか、上昇した血中ＧＬＰ−１濃度を維持するか、又は上昇した血中ＧＬＰ−１濃度の低下を抑制することをいう。 In the present specification, “GLP-1 secretion promotion” means promoting GLP-1 secretion in vivo caused by ingestion of a meal. Alternatively, “GLP-1 secretion promotion” mainly refers to whether the increase in blood GLP-1 concentration associated with GLP-1 secretion in vivo, which occurs mainly after meals, is maintained or the increased blood GLP-1 concentration is maintained. Or to suppress a decrease in the elevated blood GLP-1 concentration.
本明細書において、「ＧＩＰ分泌抑制」とは、食事を摂取することで引き起こされる生体内でのＧＩＰ分泌を抑制することを意味する。あるいは、「ＧＩＰ分泌抑制」とは、主として食後に生じる生体内でのＧＩＰ分泌に伴う血中ＧＩＰ濃度の上昇を抑制するか、又は上昇した血中ＧＩＰ濃度の低下を促進することをいう。 In this specification, “GIP secretion suppression” means suppression of GIP secretion in a living body caused by ingestion of a meal. Alternatively, “GIP secretion suppression” refers to suppressing an increase in blood GIP concentration accompanying GIP secretion in vivo, which occurs mainly after meals, or promoting a decrease in the increased blood GIP concentration.
本明細書において、「ペプチドＹＹ（ＰＹＹ）分泌促進」とは、主として食後に生じる生体内でのペプチドＹＹ分泌を促進することを意味する。あるいは、「ペプチドＹＹ（ＰＹＹ）分泌促進」とは、生体内でのペプチドＹＹ分泌に伴う血中ペプチドＹＹ濃度上昇を増強するか、上昇した血中ペプチドＹＹ濃度を維持するか、又は上昇した血中ペプチドＹＹ濃度の低下を抑制することをいう。 In the present specification, the “promotion of secretion of peptide YY (PYY)” means to promote secretion of peptide YY in vivo mainly occurring after meal. Alternatively, “peptide YY (PYY) secretion promotion” means that the increase in blood peptide YY concentration accompanying the secretion of peptide YY in vivo is increased, the increased blood peptide YY concentration is maintained, or the increased blood This refers to inhibiting the decrease in the concentration of medium peptide YY.
本発明における「食後」とは摂取した食事中の炭水化物がおおむね吸収されるまでの時間を指し、食事の摂取後の直後（０分）から６時間後まで、好ましくは５時間後まで、より好ましくは４時間後まで、さらに好ましくは３時間後までの時間を指す（Ｄｉａｂｅｔｅ Ｃａｒｅ，２００１，２４（４）：７７５−７７８）。 The term “after meal” in the present invention refers to the time until carbohydrates in the ingested meal are generally absorbed, from immediately after taking the meal (0 minutes) to 6 hours later, preferably after 5 hours, more preferably Means after 4 hours, more preferably after 3 hours (Diabete Care, 2001, 24 (4): 775-778).
本明細書において、「非治療的」とは、医療行為、すなわち治療による人体への処置行為を含まない概念である。 In the present specification, “non-therapeutic” is a concept that does not include a medical act, that is, a treatment act on the human body by therapy.
本明細書において、「改善」とは、疾患、症状又は状態の好転、疾患、症状又は状態の悪化の防止又は遅延、あるいは疾患又は症状の進行の逆転、防止又は遅延をいう。 As used herein, “improvement” refers to improvement of a disease, symptom or condition, prevention or delay of worsening of the disease, symptom or condition, or reversal, prevention or delay of progression of a disease or symptom.
本明細書において、「予防」とは、個体における疾患若しくは症状の発症の防止又は遅延、あるいは個体の疾患若しくは症状の発症の危険性を低下させることをいう。 As used herein, “prevention” refers to preventing or delaying the onset of a disease or symptom in an individual, or reducing the risk of developing an individual's disease or symptom.
アルギン酸は、全ての褐藻類に細胞壁間物質として分布するウロン酸（β−Ｄ−マンヌロン酸とα−Ｌ−グルロン酸）を主要構成糖とする高分子酸性多糖であり、１構成単位に１つのカルボキシル基を持つ。本発明に用いるアルギン酸又はその塩において、β−Ｄ−マンヌロン酸とα−Ｌ−グルロン酸の割合や配列順序は特に制限されない。したがって、本発明においては、β−Ｄ−マンヌロン酸のみからなるブロック、α−Ｌ−グルロン酸のみからなるブロック、両者が混合しているブロックの全てを有するアルギン酸又はその塩を使用してもよいし、そのいずれか１種又は２種からなるアルギン酸又はその塩を使用してもよいが、このうち、アルギン酸の塩を使用することが好ましい。 Alginic acid is a high-molecular acidic polysaccharide composed mainly of uronic acid (β-D-mannuronic acid and α-L-guluronic acid) distributed as a cell wall substance in all brown algae, and is one in each structural unit. Has a carboxyl group. In the alginic acid or a salt thereof used in the present invention, the ratio and sequence order of β-D-mannuronic acid and α-L-guluronic acid are not particularly limited. Therefore, in the present invention, alginic acid having a block consisting of only β-D-mannuronic acid, a block consisting of only α-L-guluronic acid, or a block in which both are mixed, or a salt thereof may be used. However, alginic acid or a salt thereof composed of any one or two of them may be used, and among these, it is preferable to use a salt of alginic acid.
本発明に用いるアルギン酸の塩としては、アルギン酸の金属塩が好ましく、アルギン酸の一価の金属イオンの塩がより好ましく、アルギン酸ナトリウム、アルギン酸カリウムがさらに好ましく、アルギン酸カリウムがなお好ましい。本発明に用いるアルギン酸塩は、一価の金属イオンの塩を１０質量％以上含み、好ましくはカリウム塩を１４質量％以上含み得る。また、本発明に用いるアルギン酸塩を構成する金属イオンは、異なる種類の金属イオンを含んでいてもよいが、好ましくは、該金属イオン中の８０％以上は一価の金属イオンであり、より好ましくはカリウムイオンである。 As the salt of alginic acid used in the present invention, a metal salt of alginic acid is preferable, a salt of a monovalent metal ion of alginic acid is more preferable, sodium alginate and potassium alginate are further preferable, and potassium alginate is still more preferable. The alginate used in the present invention contains 10% by mass or more of a monovalent metal ion salt, preferably 14% by mass or more of a potassium salt. In addition, the metal ions constituting the alginate used in the present invention may contain different types of metal ions. Preferably, 80% or more of the metal ions are monovalent metal ions, and more preferably. Is potassium ion.
本発明において用いられるアルギン酸又はその塩は、高速液体クロマトグラフィー（ＨＰＬＣ）法で測定した重量平均分子量は、肥満予防及び／又は改善効果の点から、２０万超が好ましく、２１万以上がより好ましく、２５万以上がさらに好ましく、２７万以上がなお好ましい。また、配合時の取り扱いなどの点から重量平均分子量は９０万以下が好ましく、６０万以下がより好ましく、５０万以下がさらに好ましく、４５万以下がなお好ましく、４１万以下がさらになお好ましい。 Alginic acid or a salt thereof used in the present invention has a weight average molecular weight measured by a high performance liquid chromatography (HPLC) method, preferably more than 200,000, more preferably 210,000 or more, from the viewpoint of obesity prevention and / or improvement effect. 250,000 or more is more preferable, and 270,000 or more is more preferable. In view of handling at the time of blending, the weight average molecular weight is preferably 900,000 or less, more preferably 600,000 or less, further preferably 500,000 or less, still more preferably 450,000 or less, and still more preferably 410,000 or less.
よって、本発明において用いられるアルギン又はその塩の分子量は、２０万超〜９０万以下であればよいが、好ましい実施形態においては、２０万超〜６０万以下、より好ましくは２０万超〜５０万以下、さらに好ましくは２０万超〜４５万以下、なお好ましくは２０万超〜４１万以下、さらになお好ましくは２０万超〜３５万以下である。より好ましい実施形態においては、２１万以上９０万以下、好ましくは２１万以上６０万以下、より好ましくは２１万以上５０万以下、さらに好ましくは２１万以上４５万以下、なお好ましくは２１万以上４１万以下、さらになお好ましくは２１万超〜３５万以下である。さらに好ましい実施形態においては、２５万以上６０万以下、好ましくは２５万以上５０万以下、より好ましくは２５万以上４５万以下、さらに好ましくは２５万以上４１万以下である。なお好ましい実施形態においては、２７万以上６０万以下、好ましくは２７万以上５０万以下、より好ましくは２７万以上４５万以下、さらに好ましくは２７万以上４１万以下である。また、これら好ましい重量平均分子量範囲を有するアルギン酸カリウムを使用することがことさら好ましい。 Therefore, the molecular weight of algin or a salt thereof used in the present invention may be more than 200,000 to 900,000, but in a preferred embodiment, more than 200,000 to 600,000, more preferably more than 200,000 to 50. 10,000 or less, more preferably more than 200,000 to 450,000 or less, still more preferably more than 200,000 to 410,000 or less, still more preferably more than 200,000 to 350,000. In a more preferred embodiment, 210,000 or more and 900,000 or less, preferably 210,000 or more and 600,000 or less, more preferably 210,000 or more and 500,000 or less, further preferably 210,000 or more and 450,000 or less, and still more preferably 210,000 or more and 41 or more. 10,000 or less, more preferably more than 210,000 to 350,000 or less. In a more preferred embodiment, it is from 250,000 to 600,000, preferably from 250,000 to 500,000, more preferably from 250,000 to 450,000, and even more preferably from 250,000 to 410,000. In a preferred embodiment, it is from 270,000 to 600,000, preferably from 270,000 to 500,000, more preferably from 270,000 to 450,000, and even more preferably from 270,000 to 410,000. It is further preferable to use potassium alginate having these preferable weight average molecular weight ranges.
本発明のアルギン酸又はその塩は、加圧加熱分解（特開平６−７０９３号公報）、または酵素分解（特開平２−３０３４６８号公報、特開平３−９４６７５号公報、特開平４−１６９１８９号公報、特開平６−２４５７６７号公報、特開平６−２１７７７４号公報）等の方法により製造することができる。すなわち、例えば、原料となる高分子量アルギン酸塩や高分子量アルギン酸を、加圧加熱分解、常圧加熱分解、酵素分解等によって所望の分子量に低分子化し、必要に応じて中和、脱水、凍結乾燥することにより得ることができる。分子量の調整は、例えば、加熱分解では、反応ｐＨ、反応温度、反応時間等を制御することにより行うことができる。 The alginic acid or a salt thereof of the present invention is decomposed under pressure (JP-A-6-7093) or enzymatic decomposition (JP-A-2-303468, JP-A-3-94675, JP-A-4-169189). , JP-A-6-245767, JP-A-6-217774) and the like. That is, for example, high molecular weight alginate or high molecular weight alginic acid as a raw material is reduced to a desired molecular weight by pressure thermal decomposition, atmospheric pressure thermal decomposition, enzymatic decomposition, etc., and neutralization, dehydration, lyophilization as necessary Can be obtained. The molecular weight can be adjusted, for example, by controlling the reaction pH, reaction temperature, reaction time and the like in the thermal decomposition.
後記実施例に示すように、平均分子量が２０万超のアルギン酸又はその塩は、糖質、脂質、蛋白質を同時摂取した後に、血中ＧＬＰ−１及びＰＹＹを上昇させ、他方血中ＧＩＰ上昇を低下させる作用を有する。しかもそれらの作用は、従来知られていた低分子量アルギン酸又はその塩の作用と比べてはるかに優れている。 As shown in the examples below, alginic acid having an average molecular weight of more than 200,000 or a salt thereof increases blood GLP-1 and PYY after simultaneously ingesting carbohydrates, lipids, and proteins, while increasing blood GIP. Has the effect of reducing. Moreover, their action is far superior to that of conventionally known low molecular weight alginic acid or a salt thereof.
したがって、重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩（以下、本発明のアルギン酸又はその塩とも称する）は、食後におけるＧＬＰ−１分泌促進、ＧＩＰ分泌抑制、ＰＹＹ分泌促進等の、消化管ホルモン分泌調節のために使用することができ、且つこれらの作用を介して、内臓脂肪蓄積抑制、肥満予防及び／又は改善等のために使用することができる。上記使用は、ヒト若しくは非ヒト動物、又はそれらに由来する検体における使用であり得、また治療的使用であっても非治療的使用であってもよい。
また本発明のアルギン酸又はその塩は、食後におけるＧＬＰ−１分泌促進剤、ＧＩＰ分泌抑制剤、ＰＹＹ分泌促進剤等の消化管ホルモン分泌調節剤を製造するため、ならびに内臓脂肪蓄積抑制剤や肥満予防及び／又は改善剤を製造するために使用することができる。
Therefore, alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof (hereinafter also referred to as alginic acid or a salt thereof of the present invention), such as GLP-1 secretion promotion, GIP secretion inhibition and PYY secretion promotion after meal, It can be used for the regulation of gastrointestinal hormone secretion, and through these actions, it can be used for suppressing visceral fat accumulation, preventing obesity and / or improving. The use may be in humans or non-human animals, or specimens derived therefrom, and may be therapeutic or non-therapeutic.
The alginic acid or a salt thereof of the present invention is used to produce gastrointestinal hormone secretion regulators such as GLP-1 secretion promoters, GIP secretion inhibitors, PYY secretion promoters after meals, visceral fat accumulation inhibitors and obesity prevention. And / or can be used to produce improvers.
すなわち、一態様において、本発明は、重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩を有効成分とする消化管ホルモン分泌調節剤を提供し得る。一実施形態において、該消化管ホルモン分泌調節は、食後ＧＬＰ−１分泌促進、食後ＧＩＰ分泌抑制、又は食後ペプチドＹＹ分泌促進であり得る。別の態様において、本発明は、重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩を有効成分とする内臓脂肪蓄積抑制剤、ならびに肥満予防及び／又は改善剤を提供し得る。
上記本発明の剤は、本質的に重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩から構成されていてもよい。
That is, in one aspect, the present invention can provide a gastrointestinal hormone secretion regulator containing alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof as an active ingredient. In one embodiment, the gastrointestinal hormone secretion regulation may be postprandial GLP-1 secretion promotion, postprandial GIP secretion inhibition, or postprandial peptide YY secretion promotion. In another aspect, the present invention can provide a visceral fat accumulation inhibitor and an agent for preventing and / or improving obesity comprising alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof as an active ingredient.
The agent of the present invention may be essentially composed of alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof.
また、本発明のアルギン酸又はその塩は、食後におけるＧＬＰ−１分泌促進、ＧＩＰ分泌抑制、ＰＹＹ分泌促進等の消化管ホルモン分泌調節のため、あるいは内臓脂肪蓄積抑制や肥満予防及び／又は改善のための組成物、医薬、医薬部外品、飲食品若しくはその原料、又は飼料若しくはその原料に素材として配合することができ、あるいはその製造のために使用することができる。 Also, the alginic acid or a salt thereof of the present invention is for gastrointestinal hormone secretion regulation such as GLP-1 secretion promotion, GIP secretion suppression, PYY secretion promotion after meal, visceral fat accumulation suppression, obesity prevention and / or improvement. It can be blended as a raw material in a composition, a medicine, a quasi-drug, a food or drink or a raw material thereof, or a feed or a raw material thereof, or can be used for the production thereof.
上記組成物、医薬、医薬部外品、飲食品、飼料、又は飲食品若しくは飼料の原料は、ヒト又は非ヒト動物用として製造され、又は使用され得る。本発明のアルギン酸又はその塩は、当該組成物、医薬、医薬部外品、飲食品、飼料、又は飲食品若しくは飼料の原料に素材として配合され、食後におけるＧＬＰ−１分泌促進、ＧＩＰ分泌抑制、ＰＹＹ分泌促進等の消化管ホルモン分泌調節のため、あるいは内臓脂肪蓄積抑制や肥満予防及び／又は改善のための有効成分であり得る。 The composition, medicine, quasi-drug, food / beverage product, feed, or food / beverage product or feed material may be produced or used for human or non-human animals. Alginic acid or a salt thereof of the present invention is blended as a raw material of the composition, medicine, quasi-drug, food / beverage product, feed, or food / beverage product or feed, and promotes GLP-1 secretion after meals, GIP secretion inhibition, It may be an active ingredient for regulating gastrointestinal hormone secretion such as promotion of PYY secretion, or for inhibiting visceral fat accumulation and preventing and / or improving obesity.
上記医薬又は医薬部外品は、本発明のアルギン酸又はその塩を有効成分として含有する。当該医薬又は医薬部外品は、経口投与及び非経口投与を含む任意の投与形態で投与され得るが、好ましくは経口投与され得る。上記医薬や医薬部外品は、本発明のアルギン酸又はその塩を単独で含有していてもよく、又は薬学的に許容される担体と組み合わせて含有していてもよい。また、当該医薬や医薬部外品は、本発明のアルギン酸又はその塩の消化管ホルモン分泌調節作用が失われない限り、他の有効成分や薬理成分を含有していてもよい。 The said pharmaceutical or quasi-drug contains the alginic acid of this invention or its salt as an active ingredient. The pharmaceutical or quasi-drug can be administered in any dosage form including oral administration and parenteral administration, but can preferably be administered orally. The said pharmaceutical and quasi-drug may contain the alginic acid or its salt of this invention independently, or may contain it in combination with a pharmaceutically acceptable carrier. Moreover, the said pharmaceutical and quasi-drug may contain another active ingredient and a pharmacological component, as long as the alimentic acid or its salt of this invention does not lose the gastrointestinal hormone secretion regulation effect.
上記医薬又は医薬部外品は、本発明のアルギン酸又はその塩から、あるいは必要に応じて担体、他の有効成分や薬理成分を組みあわせて、常法により製造することができる。例えば、経口用固形製剤を調製する場合には、本発明のアルギン酸又はその塩に、賦形剤、必要に応じて結合剤、崩壊剤、滑沢剤、着色剤、矯味剤、矯臭剤等を加えた後、常法により錠剤、被覆錠剤、顆粒剤、散剤、カプセル剤等を製造することができる。また、経口用液体製剤を調製する場合は、矯味剤、緩衝剤、安定化剤、矯味剤等を加えて常法により内服液剤、シロップ剤、エリキシル剤等を製造することができる。 The above medicament or quasi-drug can be produced from the alginic acid of the present invention or a salt thereof, or in combination with a carrier, other active ingredients or pharmacological ingredients as required, according to a conventional method. For example, when preparing an oral solid preparation, the alginic acid of the present invention or a salt thereof is mixed with an excipient, and if necessary, a binder, a disintegrant, a lubricant, a coloring agent, a corrigent, a corrigent and the like. After the addition, tablets, coated tablets, granules, powders, capsules and the like can be produced by conventional methods. Moreover, when preparing a liquid preparation for oral use, a liquid preparation, a syrup, an elixir, etc. can be manufactured by a conventional method by adding a corrigent, a buffer, a stabilizer, a corrigent and the like.
上記医薬又は医薬部外品における本発明のアルギン酸又はその塩の含有量は、０．０１〜１００質量％であればよいが、好ましくは０．１〜８０質量％であり得る。より好ましくは、固形製剤とする場合には１〜５０質量％であり得、液体製剤とする場合には０．１〜２０質量％であり得る。 The content of alginic acid or a salt thereof of the present invention in the pharmaceutical or quasi-drug may be 0.01 to 100% by mass, preferably 0.1 to 80% by mass. More preferably, it may be 1 to 50% by mass in the case of a solid preparation, and 0.1 to 20% by mass in the case of a liquid preparation.
上記飲食品や飼料は、食後におけるＧＬＰ−１分泌促進、ＧＩＰ分泌抑制、ＰＹＹ分泌促進等の消化管ホルモン分泌調節機能、あるいは内臓脂肪蓄積抑制機能や、肥満予防及び／又は改善機能を有し、且つ当該機能を必要に応じて表示した飲食品、機能性飲食品、病者用飲食品、特定保健用飲食品、ペットフード等であり得る。飲食品や機能性飲食品、病者用飲食品、特定保健用飲食品としては固形の食品、ゼリーの様な常温で半固形の食品、アイスクリームや氷菓のように低温で固形又は半固形の食品、飲料の形態が含まれる。 The foods and drinks and feeds have functions of regulating gastrointestinal hormone secretion such as GLP-1 secretion promotion, GIP secretion suppression, PYY secretion promotion after meals, visceral fat accumulation suppression function, obesity prevention and / or improvement function, And it can be food / beverage products which displayed the said function as needed, functional food / beverage products, food / beverage products for sick people, food / beverage products for specific health, pet food, etc. Foods and drinks, functional foods and drinks, foods and drinks for the sick, foods and drinks for specified health use, solid foods, foods that are semisolid at room temperature such as jelly, solids or semisolids at low temperatures such as ice cream and ice confections Includes food and beverage forms.
また、上記飲食品は、内臓脂肪蓄積抑制機能や、肥満予防及び／又は改善機能を有する飲食品として、肥満を改善したい者に摂取され得る。より好ましくは、肥満を改善したい者の中でも、胃もたれや消化不良等の症状を有する者に摂取され得る。 Moreover, the said food / beverage products can be ingested by the person who wants to improve obesity as a food / beverage product which has a visceral fat accumulation inhibitory function and an obesity prevention and / or improvement function. More preferably, among those who want to improve obesity, they can be taken by those who have symptoms such as stomach upset and indigestion.
二価の金属イオンは、アルギン酸又はその塩の粘度やゲル強度に影響を与え得るため、上記飲食品中の二価の金属イオンの含有量は、当該飲食品に含まれるアルギン酸又はその塩が極端に増粘されない程度に少ない量であることが好ましい。例えば、上記飲食品中の二価の金属イオンの含有量は、該飲食品中のアルギン酸又はその塩の総量に対して、好ましくは２質量％未満であり、より好ましくは１．５質量％以下であり、さらに好ましくは１質量％以下であり、さらにより好ましくは０．５質量％以下であり、なお好ましくは０．２質量％以下であり、さらになお好ましくは０．１質量％以下であり、さらになお好ましくは０．０５質量％以下であり、さらになお好ましくは０．０１質量％以下であり得る。二価の金属イオンとしては、リン酸カルシウム及び炭酸カルシウムのような水に不溶性で胃内にて可溶性になる二価の金属イオン、乳酸カルシウムのような水溶性の二価の金属イオン、ならびに塩化カルシウム、水酸化カルシウム、クエン酸カルシウム、乳酸発酵カルシウム、貝殻焼成カルシウム、グルタミン酸カルシウムなどが挙げられる。 Since the divalent metal ion can affect the viscosity and gel strength of alginic acid or a salt thereof, the content of the divalent metal ion in the food or drink is extremely high in alginic acid or a salt thereof contained in the food or drink. The amount is preferably so small that it is not thickened. For example, the content of the divalent metal ion in the food or drink is preferably less than 2% by weight, more preferably 1.5% by weight or less, based on the total amount of alginic acid or a salt thereof in the food or drink. More preferably 1% by mass or less, still more preferably 0.5% by mass or less, still more preferably 0.2% by mass or less, and still more preferably 0.1% by mass or less. Still more preferably, it is 0.05 mass% or less, More preferably, it may be 0.01 mass% or less. Examples of divalent metal ions include divalent metal ions that are insoluble in water and soluble in the stomach, such as calcium phosphate and calcium carbonate, water-soluble divalent metal ions such as calcium lactate, and calcium chloride. Examples include calcium hydroxide, calcium citrate, lactic acid fermented calcium, shell-fired calcium, and calcium glutamate.
上記飲食品若しくは飼料、又はそれらの原料は、本発明のアルギン酸又はその塩を単独で含有していてもよく、又は他の食材や、溶剤、軟化剤、油、乳化剤、防腐剤、香科、安定剤、着色剤、酸化防止剤、保湿剤、増粘剤等の添加剤を組み合わせて含有していてもよい。当該飲食品若しくは飼料中の本発明のアルギン酸又はその塩の含有量は、０．０１〜３０質量％とするのが好ましく、０．１〜１０質量％とするのがより好ましく、１〜５質量％とするのがさらに好ましい。 The food or drink or feed, or the raw materials thereof may contain the alginic acid or a salt thereof of the present invention alone, or other foods, solvents, softeners, oils, emulsifiers, preservatives, fragrances, You may contain combining additives, such as a stabilizer, a coloring agent, antioxidant, a moisturizer, and a thickener. The content of the alginic acid or salt thereof of the present invention in the food or drink or feed is preferably 0.01 to 30% by mass, more preferably 0.1 to 10% by mass, and 1 to 5% by mass. More preferably, it is made into%.
あるいは、本発明のアルギン酸又はその塩は、食後におけるＧＬＰ−１分泌促進、ＧＩＰ分泌抑制、ＰＹＹ分泌促進等の消化管ホルモン分泌調節のため、あるいは内臓脂肪蓄積抑制や、肥満予防及び／又は改善のため、それらを必要とする対象に有効量で投与されるか又は摂取され得る。 Alternatively, the alginic acid or a salt thereof of the present invention can be used for the regulation of gastrointestinal hormone secretion such as GLP-1 secretion promotion, GIP secretion inhibition, PYY secretion promotion after meals, visceral fat accumulation inhibition, obesity prevention and / or improvement. Thus, it can be administered or ingested in an effective amount to a subject in need thereof.
本発明のアルギン酸又はその塩を投与又は摂取する対象としては、食後におけるＧＬＰ−１分泌促進、ＧＩＰ分泌抑制、ＰＹＹ分泌促進等の消化管ホルモン分泌調節を必要とする動物、あるいは内臓脂肪蓄積抑制や、肥満予防及び／又は改善を必要とする動物であり得る。動物は、好ましくはヒト又は非ヒト哺乳動物であり、より好ましくはヒトである。対象動物がヒトの場合、肥満や生活習慣病を予防又は改善したい者も対象者に含まれる。生活習慣病を予防又は改善したい者としては、糖尿病を予防又は改善したい者、糖尿病に伴う神経障害を予防又は改善したい者が含まれる。上記肥満を改善したい者の中でも、胃もたれや消化不良等の症状を有する者を対象者とすることがより好ましい。また、肥満や糖尿病等の生活習慣病に罹患していない者で胃もたれや消化不良等の症状を有する者も対象者とすることができる。一態様において、上記投与又は摂取は、美容目的で、又は健康改善等を意図して非治療的に行われ得る。 Examples of subjects to be administered or ingested alginic acid or a salt thereof of the present invention include animals that require gastrointestinal hormone secretion regulation such as GLP-1 secretion promotion, GIP secretion suppression, and PYY secretion promotion after meals, visceral fat accumulation suppression, It may be an animal in need of obesity prevention and / or improvement. The animal is preferably a human or non-human mammal, more preferably a human. When the target animal is a human, the subject also includes those who want to prevent or improve obesity and lifestyle-related diseases. Those who want to prevent or improve lifestyle-related diseases include those who want to prevent or improve diabetes and those who want to prevent or improve neuropathy associated with diabetes. Among those who want to improve the above obesity, it is more preferable to target those who have symptoms such as stomach upset and indigestion. In addition, those who are not suffering from lifestyle-related diseases such as obesity and diabetes and who have symptoms such as stomach upset and indigestion can also be targeted. In one aspect, the administration or ingestion may be performed non-therapeutically for cosmetic purposes or for the purpose of improving health or the like.
本発明のアルギン酸又はその塩の好ましい投与又は摂取量は、対象の種、体重、性別、年齢、状態又はその他の要因に従って変動し得る。投与の用量、経路、間隔、及び摂取の量や間隔は、当業者によって適宜決定され得る。例えば、ヒトに経口投与又は摂取させる場合、投与又は摂取量は、アルギン酸として、一日当り、０．００１ｇ／ｋｇ体重以上が好ましく、０．０１〜１．０ｇ／ｋｇ体重とするのがより好ましい。 The preferred administration or intake of the alginic acid or salt thereof of the present invention may vary according to the subject's species, weight, sex, age, condition or other factors. The dose, route, interval, and amount and interval of intake can be determined appropriately by those skilled in the art. For example, in the case of oral administration or ingestion to humans, the administration or intake amount is preferably 0.001 g / kg body weight or more per day as alginic acid, and more preferably 0.01 to 1.0 g / kg body weight.
本発明のアルギン酸又はその塩を内臓脂肪蓄積抑制や、肥満予防及び／又は改善のためヒトに投与又は摂取する場合の期間は、内臓脂肪蓄積抑制のためには、７日以上が好ましく、１０日以上がより好ましく、２週間以上がさらに好ましく、８週間以上がさらにより好ましい。肥満予防及び／又は改善のためには２週間以上が好ましく、４週間以上がより好ましく、８週以上がさらに好ましい。好ましい投与又は摂取の形態は、上記投与または摂取の期間に食事と同時又は食事の前後に摂取することが好ましく、食事の前後としては食事の前後１時間以内が好ましく、前後３０分以内がより好ましく、前後１０分以内がさらに好ましい。 The period when the alginic acid of the present invention or a salt thereof is administered or ingested to humans for visceral fat accumulation suppression or obesity prevention and / or improvement is preferably 7 days or more for visceral fat accumulation suppression, 10 days The above is more preferable, 2 weeks or more is further preferable, and 8 weeks or more is further more preferable. For prevention and / or improvement of obesity, 2 weeks or more is preferable, 4 weeks or more is more preferable, and 8 weeks or more is more preferable. The preferred form of administration or ingestion is preferably taken at the same time as or before or after the meal during the above administration or ingestion period. The pre- and post-meal is preferably within 1 hour before and after the meal, more preferably within 30 minutes before and after the meal. More preferably, it is within 10 minutes before and after.
本発明のアルギン酸又はその塩を食後におけるＧＬＰ−１分泌促進、ＧＩＰ分泌抑制、ＰＹＹ分泌促進等の消化管ホルモン分泌調節のためにヒトに投与または摂取する場合は、単回の投与又は摂取でも継続して投与又は摂取してもよい。継続して投与又は摂取する場合の期間は前述の内臓脂肪蓄積抑制の為の期間でも肥満予防及び／又は改善のための期間でも良い。好ましい投与又は摂取の形態は、上記単回投与又は摂取のとき、または上記継続投与又は摂取の期間に、食事と同時又は食事の前後に摂取することが好ましく、食事の前後としては食事の前後１時間以内が好ましく、前後３０分以内がより好ましく、前後１０分以内がさらに好ましい。 When the alginic acid or a salt thereof of the present invention is administered or ingested to humans for the regulation of gastrointestinal hormone secretion such as GLP-1 secretion promotion, GIP secretion inhibition, PYY secretion promotion after meals, it is continued even after single administration or ingestion It may be administered or ingested. The period of continuous administration or ingestion may be the above-mentioned period for suppressing visceral fat accumulation or the period for preventing and / or improving obesity. The preferred form of administration or ingestion is preferably taken at the same time as the meal or before or after the meal during the single administration or ingestion or during the continuous administration or ingestion period. Within 30 minutes is preferable, within 30 minutes before and after, more preferably within 10 minutes before and after.
上述した本発明の別の実施形態として、さらに以下の組成物、製造方法、あるいは用途を本明細書に開示する。 As another embodiment of the present invention described above, the following compositions, production methods, or uses are further disclosed herein.
＜１＞消化管ホルモン分泌調節のために使用される重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩。 <1> Alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof used for regulating gastrointestinal hormone secretion.
＜２＞消化管ホルモン分泌調節が食後ＧＬＰ−１分泌促進である＜１＞のアルギン酸又はその塩。 <2> Alginic acid or a salt thereof according to <1>, wherein regulation of gastrointestinal hormone secretion is promotion of postprandial GLP-1 secretion.
＜３＞消化管ホルモン分泌調節が食後ＧＩＰ分泌抑制である＜１＞のアルギン酸又はその塩。 <3> Alginic acid or a salt thereof according to <1>, wherein regulation of gastrointestinal hormone secretion is suppression of postprandial GIP secretion.
＜４＞消化管ホルモン分泌調節が食後ペプチドＹＹ分泌促進である＜１＞のアルギン酸又はその塩。 <4> Alginic acid or a salt thereof according to <1>, wherein the regulation of gastrointestinal hormone secretion is the promotion of postprandial peptide YY secretion.
＜５＞肥満予防及び／又は改善のために使用される重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩。 <5> Alginic acid or a salt thereof having a weight average molecular weight of more than 200,000 to 900,000 or less used for obesity prevention and / or improvement.
＜６＞内臓脂肪蓄積抑制のために使用される重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩。 <6> Alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof used for suppressing visceral fat accumulation.
＜７＞重量平均分子量が、２０万超〜６０万以下、好ましくは２０万超〜５０万以下、より好ましくは２０万超〜４５万以下、さらに好ましくは２０万超〜４１万以下、なお好ましくは２０万超〜３５万以下である＜１＞〜＜６＞のいずれか１に記載のアルギン酸又はその塩。 <7> The weight average molecular weight is more than 200,000 to 600,000, preferably more than 200,000 to 500,000, more preferably more than 200,000 to 450,000, more preferably more than 200,000 to 410,000, still more preferably Is alginic acid or a salt thereof according to any one of <1> to <6>, which is more than 200,000 to 350,000 or less.
＜８＞重量平均分子量が、２１万以上６０万以下、好ましくは２１万以上５０万以下、より好ましくは２１万以上４５万以下、さらに好ましくは２１万以上４１万以下、なお好ましくは２１万超〜３５万以下である＜１＞〜＜６＞のいずれか１に記載のアルギン酸又はその塩。 <8> The weight average molecular weight is 210,000 or more and 600,000 or less, preferably 210,000 or more and 500,000 or less, more preferably 210,000 or more and 450,000 or less, further preferably 210,000 or more and 410,000 or less, and more preferably more than 210,000 Alginic acid or a salt thereof according to any one of <1> to <6>, which is ˜350,000 or less.
＜９＞重量平均分子量が２５万以上６０万以下、好ましくは２５万以上５０万以下、より好ましくは２５万以上４５万以下、さらに好ましくは２５万以上４１万以下である＜１＞〜＜６＞のいずれか１に記載のアルギン酸又はその塩。 <9> The weight average molecular weight is from 250,000 to 600,000, preferably from 250,000 to 500,000, more preferably from 250,000 to 450,000, and even more preferably from 250,000 to 410,000. <1> to <6 > Alginic acid or a salt thereof according to any one of the above.
＜１０＞重量平均分子量が２７万以上６０万以下、好ましくは２７万以上５０万以下、より好ましくは２７万以上４５万以下、さらに好ましくは２７万以上４１万以下である＜１＞〜＜６＞のいずれか１に記載のアルギン酸又はその塩。 <10> The weight average molecular weight is from 270,000 to 600,000, preferably from 270,000 to 500,000, more preferably from 270,000 to 450,000, and even more preferably from 270,000 to 410,000. <1> to <6 > Alginic acid or a salt thereof according to any one of the above.
＜１１＞アルギン酸の塩がアルギン酸カリウムである＜１＞〜＜１０＞のいずれか１に記載のアルギン酸又はその塩。 <11> Alginic acid or a salt thereof according to any one of <1> to <10>, wherein the salt of alginic acid is potassium alginate.
＜１２＞アルギン酸又はその塩が飲料又は半固形形態の食品に配合され、当該飲料又は半固形形態の食品中の二価の金属イオンの濃度が、アルギン酸又はその塩の総量に対して、好ましくは２％質量未満、より好ましくは１．５％質量以下、さらに好ましくは１％質量以下、さらにより好ましくは０．５質量％以下、なお好ましくは０．２質量％以下、さらになお好ましくは０．１質量％以下、さらになお好ましくは０．０５質量％以下、さらになお好ましくは０．０１質量％以下である、＜１＞〜＜１１＞のいずれか１に記載のアルギン酸又はその塩。 <12> Alginic acid or a salt thereof is blended in a beverage or a food in a semisolid form, and the concentration of divalent metal ions in the beverage or a food in a semisolid form is preferably based on the total amount of alginic acid or a salt thereof. Less than 2% by mass, more preferably 1.5% by mass or less, further preferably 1% by mass or less, still more preferably 0.5% by mass or less, still more preferably 0.2% by mass or less, still more preferably 0.00. Alginic acid or a salt thereof according to any one of <1> to <11>, which is 1% by mass or less, more preferably 0.05% by mass or less, and still more preferably 0.01% by mass or less.
＜１３＞二価の金属イオンが乳酸カルシウム、リン酸カルシウム、炭酸カルシウム、塩化カルシウム、水酸化カルシウム、クエン酸カルシウム、乳酸発酵カルシウム、貝殻焼成カルシウム及びグルタミン酸カルシウムからなる群より選択される＜１２＞に記載のアルギン酸又はその塩。 <13> The divalent metal ion is selected from the group consisting of calcium lactate, calcium phosphate, calcium carbonate, calcium chloride, calcium hydroxide, calcium citrate, lactic acid fermented calcium, shell calcined calcium, and calcium glutamate <12> Alginic acid or a salt thereof.
＜１４＞重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩の消化管ホルモン分泌調整剤の製造のための使用。 <14> Use of alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof for producing a gastrointestinal hormone secretion regulator.
＜１５＞消化管ホルモン分泌調節剤が食後ＧＬＰ−１分泌促進剤である＜１４＞のアルギン酸又はその塩の消化管ホルモン分泌調整剤の製造のための使用。 <15> Use of alginic acid or a salt thereof according to <14>, wherein the gastrointestinal hormone secretion regulator is a postprandial GLP-1 secretion promoter, for the production of a gastrointestinal hormone secretion regulator.
＜１６＞消化管ホルモン分泌調節剤が食後ＧＩＰ分泌抑制剤である＜１４＞のアルギン酸又はその塩の消化管ホルモン分泌調整剤の製造のための使用。 <16> Use of alginic acid or a salt thereof according to <14>, wherein the gastrointestinal hormone secretion regulator is a postprandial GIP secretion inhibitor, for the production of a gastrointestinal hormone secretion regulator.
＜１７＞消化管ホルモン分泌調節剤が食後ペプチドＹＹ分泌促進である＜１４＞のアルギン酸又はその塩の消化管ホルモン分泌調整剤の製造のための使用。 <17> Use of alginic acid or a salt thereof according to <14> for the production of a gastrointestinal hormone secretion regulator, wherein the gastrointestinal hormone secretion regulator is a postprandial peptide YY secretion promoter.
＜１８＞重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩の肥満予防及び/又は改善剤の製造のための使用。 <18> Use of alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof for the prevention of obesity and / or the preparation of an improving agent.
＜１９＞重量平均分子量２０万超〜９０万以下のアルギン酸又はその塩の内臓脂肪蓄積抑制剤の製造のための使用。 <19> Use of alginic acid having a weight average molecular weight of more than 200,000 to 900,000 or less or a salt thereof for producing a visceral fat accumulation inhibitor.
＜２０＞重量平均分子量が、２０万超〜６０万以下、好ましくは２０万超〜５０万以下、より好ましくは２０万超〜４５万以下、さらに好ましくは２０万超〜４１万以下、なお好ましくは２０万超〜３５万以下である＜１４＞〜＜１９＞のいずれか１に記載のアルギン酸又はその塩の消化管ホルモン分泌調節剤、肥満予防及び／又は改善剤、または内臓脂肪蓄積抑制剤の製造のための使用。 <20> The weight average molecular weight is more than 200,000 to 600,000, preferably more than 200,000 to 500,000, more preferably more than 200,000 to 450,000, more preferably more than 200,000 to 410,000, still more preferably <14>-<19>, wherein alginic acid or a salt thereof is a gastrointestinal hormone secretion regulator, obesity prevention and / or amelioration agent, or visceral fat accumulation inhibitor Use for manufacturing.
＜２１＞重量平均分子量が、２１万以上６０万以下、好ましくは２１万以上５０万以下、より好ましくは２１万以上４５万以下、さらに好ましくは２１万以上４１万以下、なお好ましくは２１万以上〜３５万以下である＜１４＞〜＜１９＞のいずれか１に記載のアルギン酸又はその塩の消化管ホルモン分泌調節剤、肥満予防及び／又は改善剤、または内臓脂肪蓄積抑制剤の製造のための使用。 <21> The weight average molecular weight is 210,000 or more and 600,000 or less, preferably 210,000 or more and 500,000 or less, more preferably 210,000 or more and 450,000 or less, further preferably 210,000 or more and 410,000 or less, and more preferably 210,000 or more For production of a gastrointestinal hormone secretion regulator, obesity prevention and / or amelioration agent, or visceral fat accumulation inhibitor of alginic acid or a salt thereof according to any one of <14> to <19>, which is ˜350,000 or less Use of.
＜２２＞重量平均分子量が２５万以上６０万以下、好ましくは２５万以上５０万以下、より好ましくは２５万以上４５万以下、さらに好ましくは２５万以上４１万以下である＜１４＞〜＜１９＞のいずれか１に記載のアルギン酸又はその塩の消化管ホルモン分泌調節剤、肥満予防及び／又は改善剤、または内臓脂肪蓄積抑制剤の製造のための使用。 <22> The weight average molecular weight is from 250,000 to 600,000, preferably from 250,000 to 500,000, more preferably from 250,000 to 450,000, and even more preferably from 250,000 to 410,000. <14> to <19 > Use of alginic acid or a salt thereof according to any one of the above for production of a gastrointestinal hormone secretion regulator, obesity prevention and / or amelioration agent, or visceral fat accumulation inhibitor.
＜２３＞重量平均分子量が２７万以上６０万以下、好ましくは２７万以上５０万以下、より好ましくは２７万以上４５万以下、さらに好ましくは２７万以上４１万以下である＜１４＞〜＜１９＞のいずれか１に記載のアルギン酸又はその塩の消化管ホルモン分泌調節剤、肥満予防及び／又は改善剤、または内臓脂肪蓄積抑制剤の製造のための使用。 <23> The weight average molecular weight is 270,000 to 600,000, preferably 270,000 to 500,000, more preferably 270,000 to 450,000, and even more preferably 270,000 to 410,000, <14> to <19 > Use of alginic acid or a salt thereof according to any one of the above for production of a gastrointestinal hormone secretion regulator, obesity prevention and / or amelioration agent, or visceral fat accumulation inhibitor.
＜２４＞アルギン酸の塩がアルギン酸カリウムである＜１４＞〜＜２３＞のいずれか１に記載のアルギン酸又はその塩の消化管ホルモン分泌調節剤、肥満予防及び／又は改善剤、または内臓脂肪蓄積抑制剤の製造のための使用。 <24> The alginic acid salt is potassium alginate, <14> to <23>, wherein alginic acid or a salt thereof is a gastrointestinal hormone secretion regulator, obesity prevention and / or improvement agent, or visceral fat accumulation suppression Use for the manufacture of agents.
＜２５＞消化管ホルモン分泌調節剤、肥満予防及び／又は改善剤、または内臓脂肪蓄積抑制剤が飲料又は半固形形態の食品の形態であり、当該飲料又は半固形形態の食品中の二価の金属イオンの濃度が、アルギン酸又はその塩の総量に対して、好ましくは２％質量未満、より好ましくは１．５％質量以下、さらに好ましくは１％質量以下、さらにより好ましくは０．５質量％以下、なお好ましくは０．２質量％以下、さらになお好ましくは０．１質量％以下、さらになお好ましくは０．０５質量％以下、さらになお好ましくは０．０１質量％以下である、＜１４＞〜＜２４＞のいずれか１に記載のアルギン酸又はその塩の消化管ホルモン分泌調節剤、肥満予防及び／又は改善剤、または内臓脂肪蓄積抑制剤の製造のための使用。 <25> Gastrointestinal hormone secretion regulator, obesity prevention and / or amelioration agent, or visceral fat accumulation inhibitor is in the form of a beverage or a food product in a semi-solid form. The concentration of metal ions is preferably less than 2% by mass, more preferably 1.5% by mass or less, still more preferably 1% by mass or less, and even more preferably 0.5% by mass with respect to the total amount of alginic acid or a salt thereof. Or less, preferably 0.2% by mass or less, more preferably 0.1% by mass or less, still more preferably 0.05% by mass or less, and still more preferably 0.01% by mass or less. <14> Use of alginic acid or a salt thereof according to any one of to <24> for the production of a gastrointestinal hormone secretion regulator, obesity prevention and / or amelioration agent, or visceral fat accumulation inhibitor.
＜２６＞二価の金属イオンが乳酸カルシウム、リン酸カルシウム、炭酸カルシウム、塩化カルシウム、水酸化カルシウム、クエン酸カルシウム、乳酸発酵カルシウム、貝殻焼成カルシウム及びグルタミン酸カルシウムからなる群より選択される＜２５＞に記載のアルギン酸又はその塩の消化管ホルモン分泌調節剤、肥満予防及び／又は改善剤、または内臓脂肪蓄積抑制剤の製造のための使用。 <26> The <25> described in <25>, wherein the divalent metal ion is selected from the group consisting of calcium lactate, calcium phosphate, calcium carbonate, calcium chloride, calcium hydroxide, calcium citrate, lactic acid fermented calcium, shell calcined calcium, and calcium glutamate Of alginic acid or a salt thereof for the production of a gastrointestinal hormone secretion regulator, an obesity prevention and / or amelioration agent, or a visceral fat accumulation inhibitor.
製造例１ アルギン酸カリウム（重量平均分子量約２１万）の調製
アルギン酸（ダックアシッドＡ Ｌｏｔ．Ｘ−２７０２）：株式会社フードケミファ）を２％溶液に調整し、水酸化カリウムを加えてｐＨ７になるように中和した。次いで、８０％エタノール溶液になるようにエタノールを加えて、アルギン酸塩を沈殿させた。その後、遠心分離（３０００ｒｐｍ，１０ｍｉｎ）により沈殿物を回収後、乾燥して、アルギン酸カリウムを調製した。得られたアルギン酸カリウムの重量平均分子量を後述の方法にて計測をしたところ、約２１万（２０７，６０５）であった。
Production Example 1 Preparation of potassium alginate (weight average molecular weight of about 210,000) Alginic acid (Duck Acid A Lot. X-2702): Food Chemifa Co., Ltd. was adjusted to a 2% solution, and potassium hydroxide was added to reach pH 7. Neutralized. Subsequently, ethanol was added so that it might become an 80% ethanol solution, and the alginate was precipitated. Thereafter, the precipitate was collected by centrifugation (3000 rpm, 10 min) and then dried to prepare potassium alginate. When the weight average molecular weight of the obtained potassium alginate was measured by the method described later, it was about 210,000 (207,605).
製造例２ アルギン酸カリウム（重量平均分子量約２．５万）の調製
アルギン酸（ダックアシッドＡ、Ｌｏｔ．Ｘ−２７０２：株式会社紀文フードケミファ）を５％溶液に調整し、１００℃、１２０分間加熱分解した。次いで、水酸化カリウムを加えてｐＨ７になるように中和し、その後、８０％エタノール溶液になるようにエタノールを加えて、アルギン酸塩を沈殿させた。その後、遠心分離（３０００ｒｐｍ，１０ｍｉｎ）により沈殿物を回収後、乾燥して、アルギン酸カリウムを調製した。得られたアルギン酸カリウムの重量平均分子量を後述の方法にて計測をしたところ、約２．５万（２５，８０１）であった。
Production Example 2 Preparation of potassium alginate (weight average molecular weight of about 25,000) Alginic acid (Duck Acid A, Lot. X-2702: Kibun Food Chemifa Co., Ltd.) was adjusted to a 5% solution and thermally decomposed at 100 ° C. for 120 minutes. did. Next, potassium hydroxide was added to neutralize to pH 7, and then ethanol was added to obtain an 80% ethanol solution to precipitate alginate. Thereafter, the precipitate was collected by centrifugation (3000 rpm, 10 min) and then dried to prepare potassium alginate. When the weight average molecular weight of the obtained potassium alginate was measured by the method described later, it was about 25,000 (25,801).
製造例３ アルギン酸カリウム（重量平均分子量約５．２万）の調製
アルギン酸（ダックアシッドＡ、Ｌｏｔ．Ｘ−２７０２：株式会社紀文フードケミファ）を５％溶液に調整し、１００℃、４５分間加熱分解した。次いで、水酸化カリウムを加えてｐＨ７になるように中和し、その後、８０％エタノール溶液になるようにエタノールを加えて、アルギン酸塩を沈殿させた。その後、遠心分離（３０００ｒｐｍ，１０ｍｉｎ）により沈殿物を回収後、乾燥して、アルギン酸カリウムを調製した。得られたアルギン酸カリウムの重量平均分子量を後述の方法にて計測をしたところ、約５．２万（５２，１６３）であった。
Production Example 3 Preparation of potassium alginate (weight average molecular weight of about 52,000) Alginic acid (Duck Acid A, Lot. X-2702: Kibun Food Chemifa Co., Ltd.) was adjusted to a 5% solution and thermally decomposed at 100 ° C. for 45 minutes. did. Next, potassium hydroxide was added to neutralize to pH 7, and then ethanol was added to obtain an 80% ethanol solution to precipitate alginate. Thereafter, the precipitate was collected by centrifugation (3000 rpm, 10 min) and then dried to prepare potassium alginate. When the weight average molecular weight of the obtained potassium alginate was measured by the method described later, it was about 52,000 (52,163).
アルギン酸の平均分子量の測定（重量平均分子量測定法）
アルギン酸の重量平均分子量は高速液体クロマトグラフィー（ＨＰＬＣ）にて測定した。アルギン酸（塩）を０．１ｇ取り、蒸留水で０．１％溶液になるように定容して得られたものをＨＰＬＣ用分析試料とした。
ＨＰＬＣ操作条件は以下の通りであった。分子量算出用の検量線には、標準プルラン（昭和電工（株）製 Ｓｈｏｄｅｘ ＳＴＡＮＤＡＲＤ Ｐ−８２）を用いた。ＨＰＬＣ用分析試料をＨＰＬＣに１００μＬ注入し、得られたクロマトチャートより、試料中のアルギン酸の重量平均分子量を算出した。
＜ＨＰＬＣ操作条件＞
カラム：
（１）Super AW-L（ガードカラム）：東ソー（株）製
（２）TSK-GEL Super AW4000（GPC用カラム）：排除限界分子量4×105 PEO/DMF、
長さ15cm，内径6mm、東ソー（株）製
（３）TSK-GEL Super AW2500（GPC用カラム）：排除限界分子量2×103 PEO/DMF、
長さ15cm，内径6mm、東ソー（株）製
上記カラムはAW-L，AW4000，AW2500の順で連結する。
カラム温度：40℃
検出器：示差屈折計
移動相：0.2 mol/L硝酸ナトリウム水溶液
流速：0.6 mL/min
注入量：100 μL
Measurement of average molecular weight of alginic acid (weight average molecular weight measurement method)
The weight average molecular weight of alginic acid was measured by high performance liquid chromatography (HPLC). An analytical sample for HPLC was obtained by taking 0.1 g of alginic acid (salt) and making a fixed volume of 0.1% solution with distilled water.
The HPLC operating conditions were as follows. A standard pullulan (Shodex STANDARD P-82 manufactured by Showa Denko KK) was used for the calibration curve for molecular weight calculation. 100 μL of the analytical sample for HPLC was injected into the HPLC, and the weight average molecular weight of alginic acid in the sample was calculated from the obtained chromatographic chart.
<HPLC operating conditions>
column:
(1) Super AW-L (guard column): manufactured by Tosoh Corporation (2) TSK-GEL Super AW4000 (column for GPC): exclusion molecular weight 4 × 10 5 PEO / DMF,
Length 15cm, inner diameter 6mm, manufactured by Tosoh Corporation (3) TSK-GEL Super AW2500 (GPC column): exclusion limit molecular weight 2 × 10 3 PEO / DMF,
Length 15 cm, inner diameter 6 mm, manufactured by Tosoh Corporation The above columns are connected in the order of AW-L, AW4000, and AW2500.
Column temperature: 40 ° C
Detector: Differential refractometer Mobile phase: 0.2 mol / L sodium nitrate aqueous solution Flow rate: 0.6 mL / min
Injection volume: 100 μL
実施例１ アルギン酸カリウム（重量平均分子量約２１万）の食後ＧＩＰ分泌抑制効果
（１−１ 試験試料）
試験試料として、重量平均分子量約２１万のアルギン酸カリウム（製造例１）（以下、「アルギン酸Ｋ（平均分子量２１万）」と記載する）、又は重量平均分子量約２．５万のアルギン酸カリウム（製造例２）（以下、「アルギン酸Ｋ（平均分子量２．５万）」と記載する）を用いた。
（１−２ 試験動物）
１０〜１１週齢の雄性マウスＣ５７ＢＬ／６Ｊ Ｊｃｌ（日本クレア）を用いた。各群Ｎ＝６とした。
（１−３ 経口投与サンプルの調製と投与量）
トリオレイン（Ｇｌｙｃｅｒｙｌ ｔｒｉｏｌｅａｔｅ：Ｓｉｇｍａ−Ａｌｄｒｉｃｈ製）をレシチン（卵製）（和光純薬）とアルブミン（ウシ血清由来）（Ｓｉｇｍａ−Ａｌｄｒｉｃｈ製）を用いて乳化し、乳液を調製した。この乳液に、上述の試験試料を添加し、最終濃度が試験試料５（ｗ／ｗ）％、トリオレイン５（ｗ／ｗ）％、乳化剤（レシチン０．２（ｗ／ｗ）％、アルブミン１．０（ｗ／ｗ）％）となるよう、経口投与試験サンプルを調製した。なお、コントロールは、試験試料を添加しない乳液のみとした。動物に対する経口投与量は下表１のとおりである。
Example 1 Postprandial GIP secretion inhibitory effect of potassium alginate (weight average molecular weight of about 210,000) (1-1 test sample)
As a test sample, potassium alginate having a weight average molecular weight of about 210,000 (Production Example 1) (hereinafter referred to as “alginate K (average molecular weight 210,000)”) or potassium alginate having a weight average molecular weight of about 25,000 (manufacturing) Example 2) (hereinafter referred to as “alginic acid K (average molecular weight 25,000)”) was used.
(1-2 test animals)
10-11 week old male mice C57BL / 6J Jcl (CLEA Japan) were used. Each group was N = 6.
(1-3 Preparation and dosage of oral administration sample)
Triolein (Glyceryl trioleate: manufactured by Sigma-Aldrich) was emulsified with lecithin (manufactured by egg) (Wako Pure Chemical Industries) and albumin (derived from bovine serum) (manufactured by Sigma-Aldrich) to prepare an emulsion. The above test sample was added to this emulsion, and the final concentrations were 5% (w / w) test sample, 5% (w / w) triolein, 0.2% emulsifier (lecithin 0.2 (w / w), albumin 1 0.0 (w / w)%), an oral administration test sample was prepared. In addition, the control was only an emulsion with no test sample added. The oral dosage for animals is shown in Table 1 below.
（１−４ 経口投与試験）
一晩絶食させたマウスをジエチルエーテル麻酔下、眼窩静脈よりヘパリン処理ヘマトクリット毛細管（ＶＩＴＲＥＸ製）を用い、初期採血を行った。その後、経口投与サンプルを経口ゾンデ針にて胃内投与し、１０分、３０分、１、２時間後にジエチルエーテル麻酔下、眼窩静脈より採血を行った。
ヘパリン処理ヘマトクリット毛細管で採取した血液は血漿分離まで氷冷下で保存後、１１０００ｒｐｍにて５分間遠心し、血漿を得た。得られた血漿からＲａｔ／Ｍｏｕｓｅ ＧＩＰ（ｔｏｔａｌ）ＥＬＩＳＡ Ｋｉｔ（Ｍｉｌｌｉｐｏｒｅ ｃｏ．製）を用いて血中ＧＩＰ濃度を測定した。
（１−５ データ解析および統計学的検定法）
サンプル投与後２時間後までの血中ＧＩＰについて、個体ごとの最大値（個体によって１０分または３０分）を求め、平均±標準誤差（Ｓ．Ｅ．）を算出した。群間の統計学的有意差については、分散分析によって有意性（Ｐ＜０．０５）が認められた場合、多重比較検定（Ｆｉｓｈｅｒ’ｓ ＰＬＳＤ法）を実施した。
(1-4 Oral administration test)
Mice fasted overnight were subjected to initial blood sampling using heparinized hematocrit capillary tubes (manufactured by VITREX) from the orbital vein under anesthesia with diethyl ether. Thereafter, the sample for oral administration was intragastrically administered with an oral sonde needle, and blood was collected from the orbital vein under diethyl ether anesthesia 10 minutes, 30 minutes, 1 and 2 hours later.
Blood collected with a heparinized hematocrit capillary was stored under ice cooling until plasma separation, and then centrifuged at 11000 rpm for 5 minutes to obtain plasma. From the obtained plasma, blood GIP concentration was measured using Rat / Mouse GIP (total) ELISA Kit (manufactured by Millipore co.).
(1-5 Data analysis and statistical testing)
For blood GIP up to 2 hours after sample administration, the maximum value for each individual (10 minutes or 30 minutes depending on the individual) was determined, and the mean ± standard error (SE) was calculated. For statistically significant differences between groups, a multiple comparison test (Fisher's PLSD method) was performed when significance (P <0.05) was found by analysis of variance.
（１−６ 結果）
サンプル投与後の最大血中ＧＩＰ値を図１に示す。アルギン酸Ｋ（平均分子量２．５万）及びアルギン酸Ｋ（平均分子量２１万）は、いずれもコントロール群に比べて食後の最大血中ＧＩＰ値が有意に低く、血中ＧＩＰ分泌抑制効果が認められた。さらにアルギン酸Ｋ（平均分子量２１万）とアルギン酸Ｋ（平均分子量２．５万）とを比較すると、アルギン酸Ｋ（平均分子量２１万）の方が最大血中ＧＩＰ値が低かった。この結果から、アルギン酸Ｋ（平均分子量２１万）はアルギン酸Ｋ（平均分子量２．５万）に比べ、食後血中ＧＩＰ分泌抑制効果に優れることが明らかとなった。
(1-6 result)
The maximum blood GIP value after sample administration is shown in FIG. Both alginic acid K (average molecular weight 25,000) and alginic acid K (average molecular weight 210,000) had significantly lower postprandial blood GIP values compared to the control group, and a blood GIP secretion inhibitory effect was observed. . Further, comparing alginic acid K (average molecular weight 210,000) and alginic acid K (average molecular weight 25,000), alginic acid K (average molecular weight 210,000) had a lower maximum blood GIP value. From this result, it was revealed that alginic acid K (average molecular weight 210,000) is more effective in suppressing postprandial blood GIP secretion than alginic acid K (average molecular weight 25,000).
実施例２ アルギン酸カリウム（重量平均分子量約４１万）のヒトに対する食後消化管ホルモン分泌調節効果
（２−１ 試験試料）
試験試料として、重量平均分子量約４１万（４１０，０００）のアルギン酸カリウム（キミカアルギンＫＬ−１（（株）キミカ製、Ｌｏｔ．０Ｌ０８００２）（以下、「アルギン酸Ｋ（平均分子量４１万）」と記載する））、又は重量平均分子量約５万のアルギン酸カリウム（キミカアルギンＫ試作品（（株）キミカ製、Ｌｏｔ．７Ｅ２８０４１）（本実施例において、以下「アルギン酸Ｋ（平均分子量５万）」と記載する））を用いた。
（２−２ 対象）
健常成人男性１０名（平均年齢３６．８歳）
（２−３ 試験飲料）
（１）対照飲料（試験試料未含有の市販麦茶１００ｇ）
（２）アルギン酸Ｋ（平均分子量４１万）含有飲料（市販麦茶９７ｇ中に試験試料３ｇ含有）
（３）アルギン酸Ｋ（平均分子量５万）含有飲料（市販麦茶９７ｇ中に試験試料３ｇ含有）
（２−４ 方法）
１人の試験参加者に対し、対照飲料、アルギン酸Ｋ（平均分子量４１万）含有飲料、およびアルギン酸Ｋ（平均分子量５万）含有飲料の単回摂取試験を実施する３群のクロスオーバー試験を行った。試験参加者の試験順序はランダムに割り付け、それぞれの単回摂取試験は５日間以上の間隔をあけて実施した。
試験参加者は、試験前日、夕食として指定した食事（約９００ｋｃａｌ／食、脂質約２５ｇ）を試験１３時間前に摂取した。試験当日、試験参加者は試験飲料を飲んだ直後にカレーライスおよびサラダ（８００ｋｃａｌ／食、エネルギー比率Ｐ：Ｆ：Ｃ＝１４：２６：６０％）を摂取し、経時的に６時間後まで採血を行った。血液採取用採血管にはＢＤ安定化剤入り採血管Ｐ７００（ＤＰＰ−ＩＶ阻害剤、ＥＤＴＡ２Ｋ入り、日本ベクトン・ディッキンソン（株）製）を用い、採血後すみやかにプロテアーゼ阻害剤（Ｓｉｇｍａ−Ａｌｄｒｉｃｈ製）、セリンプロテアーゼ阻害剤（ロシュ・ダイアグノスティックス（株）製）を添加した。定法により得られた血漿についてＧＩＰ（ｔｏｔａｌ）、ＰＹＹ（ｔｏｔａｌ）、ＧＬＰ−１（ａｃｔｉｖｅ）をそれぞれＨｕｍａｎ ＧＩＰ（ｔｏｔａｌ）ＥＬＩＳＡ Ｋｉｔ（Ｍｉｌｌｉｐｏｒｅ製）、ＭＩＬＬＩＰＬＥＸ ＭＡＰ Ｈｕｍａｎ Ｍｅｔａｂｏｌｉｃ Ｈｏｒｍｏｎｅ Ｐａｎｅ（Ｍｉｌｌｉｐｏｒｅ製、測定機器：ＢｉｏＰｌｅｘ２００システム（Ｂｉｏ Ｒａｄ製））、Ｇｌｕｃａｇｏｎ−Ｌｉｋｅ Ｐｅｐｔｉｄｅ−１（ａｃｔｉｖｅ）ＥＬＩＳＡ Ｋｉｔ（Ｍｉｌｌｉｐｏｒｅ製）を用いて測定した。
（２−５ データ解析および統計学的検定法）
各測定について、平均±標準誤差（Ｓ．Ｅ．）を算出した。群間の統計学的有意差については、対応のあるｔ検定を行い、有意水準５％未満の場合にはＰ値を表記した。
Example 2 Postprandial gastrointestinal hormone secretion regulating effect on humans of potassium alginate (weight average molecular weight of about 410,000) (2-1 test sample)
As a test sample, potassium alginate (Kimika Argin KL-1 (manufactured by Kimika Co., Ltd., Lot. 0L08002)) having a weight average molecular weight of about 410,000 (410,000) (hereinafter referred to as “alginate K (average molecular weight 410,000)” is described. )), Or potassium alginate having a weight average molecular weight of about 50,000 (Kimika Algin K prototype (manufactured by Kimika Co., Ltd., Lot. 7E28041) (hereinafter referred to as “alginic acid K (average molecular weight 50,000)”). ) Was used.
(2-2 Target)
10 healthy adult men (average age 36.8 years)
(2-3 test beverage)
(1) Control beverage (100 g of commercial barley tea containing no test sample)
(2) Alginic acid K (average molecular weight 410,000) -containing beverage (containing 3 g of test sample in 97 g of commercially available barley tea)
(3) Alginic acid K (average molecular weight 50,000) -containing beverage (containing 3 g of test sample in 97 g of commercially available barley tea)
(2-4 method)
Three groups of crossover tests were conducted on a single test participant for a control beverage, a beverage containing alginate K (average molecular weight 410,000), and a beverage containing alginate K (average molecular weight 50,000). It was. The test order of the test participants was randomly assigned, and each single intake test was conducted at intervals of 5 days or more.
The test participants took the meal designated as dinner the day before the test (about 900 kcal / meal, about 25 g lipid) 13 hours before the test. On the day of the test, the test participants took curry rice and salad (800 kcal / meal, energy ratio P: F: C = 14: 26: 60%) immediately after drinking the test beverage, and blood was collected until 6 hours over time. Went. As a blood collection tube for blood collection, a blood collection tube P700 containing a BD stabilizer (containing a DPP-IV inhibitor, EDTA2K, manufactured by Nippon Becton Dickinson Co., Ltd.) is used. Protease inhibitor (manufactured by Sigma-Aldrich) immediately after blood collection Serine protease inhibitor (Roche Diagnostics Co., Ltd.) was added. GIP (total), PYY (total), and GLP-1 (active) for plasma obtained by a conventional method were respectively Human GIP (total) ELISA Kit (manufactured by Millipore), MILLIPLEX MAP Human Metabolic Pane (manufactured by Millipore). BioPlex 200 system (manufactured by Bio Rad)) and Glucagon-Like Peptide-1 (active) ELISA Kit (manufactured by Millipore).
(2-5 Data analysis and statistical testing)
For each measurement, the mean ± standard error (SE) was calculated. For statistically significant differences between groups, a paired t-test was performed, and when the significance level was less than 5%, the P value was expressed.
（２−６ 結果）
血中ＧＩＰ、ＧＬＰ−１、ＰＹＹの経時変化を図２〜４に示した。
アルギン酸Ｋ（平均分子量５万）を食事（８００ｋｃａｌ）の直前に摂取した場合、対照飲料に比べ、食後３０分後の血中ＧＩＰが有意に低く、食後血中ＧＩＰ分泌の抑制が確認された。一方、アルギン酸Ｋ（平均分子量４１万）を食事（８００ｋｃａｌ）の直前に摂取した場合、対照飲料に比べ、食後１時間および２時間後の血中ＧＩＰが有意に低く、食後血中ＧＩＰ分泌の抑制が確認された。さらに、アルギン酸Ｋ（平均分子量５万）とアルギン酸Ｋ（平均分子量４１万）を比較すると、アルギン酸Ｋ（平均分子量４１万）の方が食後１時間後の食後血中ＧＩＰが有意に低く、食後ＧＩＰ上昇抑制に優れることが確認された（図２）。
さらに、摂取後の血中ＧＬＰ−１は、摂取６時間までの経時変化および最大血中濃度（以下、Ｃｍａｘ）のいずれもアルギン酸Ｋ（平均分子量５万）は対照飲料と差がないのに対し、アルギン酸Ｋ（平均分子量４１万）を摂取した場合、食後３０分後およびＣｍａｘが有意高く、食後のＧＬＰ−１分泌亢進が認められた（図３）。
また、摂取後の血中ＰＹＹは、摂取６時間までの経時変化は食後３０分後でアルギン酸Ｋ（平均分子量４１万）のみ対照飲料より有意に高かった。血中ＰＹＹのＣｍａｘのいずは対照飲料に比べアルギン酸Ｋ（平均分子量５万）が高かったが、さらにアルギン酸Ｋ（平均分子量４１万）の方が有意に高かった（図４）。
(2-6 results)
Changes in blood GIP, GLP-1, and PYY over time are shown in FIGS.
When alginic acid K (average molecular weight 50,000) was ingested immediately before a meal (800 kcal), blood GIP 30 minutes after meal was significantly lower than that of the control drink, and suppression of postprandial blood GIP secretion was confirmed. On the other hand, when alginic acid K (average molecular weight 410,000) was taken immediately before a meal (800 kcal), blood GIP after 1 hour and 2 hours after meal was significantly lower than that of the control drink, and suppression of blood GIP secretion after meal was suppressed. Was confirmed. Furthermore, when alginic acid K (average molecular weight 50,000) is compared with alginic acid K (average molecular weight 410,000), alginic acid K (average molecular weight 410,000) has significantly lower postprandial blood GIP after 1 hour, and postprandial GIP It was confirmed that it was excellent in suppressing elevation (FIG. 2).
In addition, the blood GLP-1 after ingestion is not different from the control drink in terms of alginic acid K (average molecular weight 50,000), both of the time course up to 6 hours and the maximum blood concentration (hereinafter referred to as Cmax). When alginic acid K (average molecular weight of 410,000) was ingested, Cmax was significantly high 30 minutes after meal and GLP-1 secretion was increased after meal (FIG. 3).
In addition, blood PYY after ingestion was significantly higher than that of the control beverage only in alginic acid K (average molecular weight 410,000) 30 minutes after meal after 30 minutes of ingestion. The Cmax of blood PYY was higher in alginic acid K (average molecular weight 50,000) than in the control beverage, but was also significantly higher in alginic acid K (average molecular weight 410,000) (FIG. 4).
実施例３ アルギン酸カリウム（重量平均分子量約２１万）の抗肥満効果
（３−１ 試験試料）
試験試料として、製造例１のアルギン酸Ｋ（平均分子量２１万）、又は重量平均分子量約５．２万のアルギン酸カリウム（製造例３）（本実施例において、以下「アルギン酸Ｋ（平均分子量５．２万）」と記載する）を用いた。
（３−２ 試験群）
試験群１〜４（各群Ｎ＝１２）は、以下の表２に記載の４つの試験食で実施した。試験食中のコーン油、ラード、カゼイン、セルロース、ＡＩＮ７６ミネラル混合、ＡＩＮ７６ビタミン混合、α化ポテト澱粉は、オリエンタル酵母工業（株）製、蔗糖は和光純薬（株）製スクロース細粒（特級）を使用した。
Example 3 Anti-obesity effect of potassium alginate (weight average molecular weight of about 210,000) (3-1 test sample)
As a test sample, alginic acid K of Production Example 1 (average molecular weight 210,000), or potassium alginate having a weight average molecular weight of about 52,000 (Production Example 3) (hereinafter referred to as “alginic acid K (average molecular weight 5.2)”. ) ”) Was used.
(3-2 study group)
Test groups 1 to 4 (each group N = 12) were conducted with four test meals described in Table 2 below. Corn oil, lard, casein, cellulose, AIN76 mineral mixture, AIN76 vitamin mixture and pregelatinized potato starch in the test meal are manufactured by Oriental Yeast Co., Ltd., and sucrose is sucrose fine granules (special grade) manufactured by Wako Pure Chemical Industries, Ltd. It was used.
（３−３ 試験動物および飼育条件）
７週齢雄性マウスＣ５７ＢＬ／６Ｊ Ｊｃｌ（日本クレア）を１週間通常食（ＣＥ−２：ｍｏｉｓｔｕｒｅ ９．３％、ｃｒｕｄｅ ｐｒｏｔｅｉｎ ２５．１％、ｃｒｕｄｅ ｆａｔ ４．８％、ｃｒｕｄｅ ｆｉｂｅｒ ４．２％、ｃｒｕｄｅ ａｓｈ ６．７％、ＮＦＥ ５０．０％：日本クレア製）で飼育後、８週齢時に初期体重がほぼ一定になるように４つの試験群に群分けした。群分け後、表２に示した試験食を用いて試験を開始し、８週後まで試験を実施した。給餌はローデンカフェを用いた自由摂食、給水は自由飲水とした。
（３−４ 体重および内臓脂肪重量の測定）
体重測定は試験開始後、週１回測定した。試験最終日は解剖直前まで自由摂食、自由飲水とした。マウスをイソフルラン吸入麻酔下で開腹し、腹部大静脈より採血を行い安楽死させた。その後、内臓脂肪（副睾丸周囲脂肪、腎周囲脂肪、後腹膜脂肪、腸間膜脂肪）を採取し、重量を測定し、その合計値を内臓脂肪量とした。
（３−５ データ解析および統計学的検定法）
各測定について、平均±標準誤差（Ｓ．Ｅ．）を算出した。群間の統計学的有意差については、分散分析によって有意性（Ｐ＜０．０５）が認められた場合、多重比較検定（Ｆｉｓｈｅｒ’ｓ ＰＬＳＤ法）を実施した。
(3-3 Test animals and rearing conditions)
7-week-old male mouse C57BL / 6J Jcl (CLEA Japan) was fed for a week (CE-2: moisture 9.3%, crude protein 25.1%, crude fat 4.8%, crude fiber 4.2%, bred in crude ash 6.7%, NFE 50.0%: manufactured by CLEA Japan), and then grouped into 4 test groups so that the initial body weight was almost constant at 8 weeks of age. After grouping, the test was started using the test meal shown in Table 2, and the test was conducted until 8 weeks later. Feeding was free food using Roden Cafe, and water supply was free drinking.
(3-4 Measurement of body weight and visceral fat weight)
Body weight was measured once a week after the start of the test. On the last day of the test, free food and free water were used until just before dissection. Mice were laparotomized under isoflurane inhalation anesthesia, blood was collected from the abdominal vena cava and euthanized. Thereafter, visceral fat (peri-testicular periphery, perirenal fat, retroperitoneal fat, mesenteric fat) was collected and weighed, and the total value was taken as the visceral fat mass.
(3-5 Data analysis and statistical testing)
For each measurement, the mean ± standard error (SE) was calculated. For statistically significant differences between groups, a multiple comparison test (Fisher's PLSD method) was performed when significance (P <0.05) was found by analysis of variance.
（３−６ 結果）
（１）体重
試験前、試験開始４週後及び８週後の体重を下表３に示した。試験開始４週後と８週後の体重は、いずれも分散分析のＰ値が５％未満であった（いずれもＰ＜０．００１）。Ｆｉｓｈｅｒ’ｓ ＰＬＳＤ検定は、高脂肪食群（試験群２）と比較し、有意水準５％未満の場合にはＰ値、５％以上の場合にはＮ．Ｓ．（not significant）を表記した。高脂肪食群（試験群２）は、低脂肪食群（試験群１）に比べて試験開始４週及び８週後の体重が有意に高く、高脂肪食摂取による肥満が認められた。アルギン酸Ｋ（平均分子量５．２万）摂取群（試験群３）では、４週及び８週後の体重はいずれも高脂肪食群（試験群２）と有意な差がなく、８週後までに明確な肥満抑制効果は認められなかった。一方、アルギン酸Ｋ（平均分子量２１万）摂取群（試験群４）では、８週後の体重が高脂肪食群（試験群２）に比べて有意に低く、肥満抑制効果が認められた。
(3-6 results)
(1) Body weight Table 3 shows the body weight before the test, 4 weeks after the start of the test, and 8 weeks after the test. The body weights at 4 weeks and 8 weeks after the start of the test were both less than 5% in P value of analysis of variance (both P <0.001). The Fisher's PLSD test is compared with the high fat diet group (Test Group 2), and the P value is 5% or more when the significance level is less than 5%. S. (Not significant) is shown. The high fat diet group (Test Group 2) was significantly higher in body weight at 4 weeks and 8 weeks after the start of the test than the low fat diet group (Test Group 1), and obesity due to high fat diet intake was observed. In the alginic acid K (average molecular weight 52,000) intake group (Study Group 3), the body weight after 4 weeks and 8 weeks was not significantly different from the high fat diet group (Study Group 2), and until 8 weeks later There was no clear obesity-inhibiting effect. On the other hand, in the alginic acid K (average molecular weight 210,000) intake group (test group 4), the body weight after 8 weeks was significantly lower than that in the high fat diet group (test group 2), and an obesity suppressing effect was observed.
（２）内臓脂肪量
各群の試験開始８週後の内臓脂肪量を下表４に示した。内臓脂肪量の分散分析のＰ値は５％未満（Ｐ＜０．０１）であった。Ｆｉｓｈｅｒ’ｓ ＰＬＳＤ検定は、高脂肪食群（試験群２）と比較し有意水準５％未満の場合にはＰ値、５％以上の場合にはＮ．Ｓ．（not significant）を表記した。
高脂肪食群（試験群２）は、低脂肪食群（試験群１）に比べて内臓脂肪量が有意に多く、高脂肪食摂取による内臓脂肪蓄積が確認された。アルギン酸Ｋ（平均分子量５．２万）摂取群（試験群３）では、内臓脂肪量は高脂肪食群（試験群２）と差がなく、８週後の時点ではアルギン酸Ｋ摂取による内臓脂肪蓄積抑制作用は明確には認められなかった。一方、アルギン酸Ｋ（平均分子量２１万）摂取群（試験群４）では、内臓脂肪重は高脂肪食群（試験群２）に比べて有意に低く、８週間摂取での内臓脂肪蓄積抑制効果が認められた。
(2) Visceral fat mass The visceral fat mass 8 weeks after the start of the test in each group is shown in Table 4 below. The P value of analysis of variance of visceral fat mass was less than 5% (P <0.01). The Fisher's PLSD test is a P value when the significance level is less than 5% as compared with the high fat diet group (Study Group 2), and N.sub. S. (Not significant) is shown.
The high-fat diet group (Test Group 2) had a significantly higher amount of visceral fat than the low-fat diet group (Test Group 1), and the visceral fat accumulation due to the intake of the high-fat diet was confirmed. In the alginic acid K (average molecular weight 52,000) intake group (Study Group 3), the visceral fat mass was not different from that in the high fat diet group (Study Group 2). The inhibitory effect was not clearly observed. On the other hand, in the alginic acid K (average molecular weight 210,000) ingestion group (test group 4), the visceral fat weight was significantly lower than in the high fat diet group (test group 2), and the visceral fat accumulation-inhibiting effect when ingested for 8 weeks. Admitted.
以上の結果から、アルギン酸Ｋ（平均分子量２１万）は、アルギン酸Ｋ（平均分子量５．２万）に比べて高脂肪食による体重増加や内臓脂肪蓄積を抑制する作用に優れ、より短期間で体重増加抑制効果や内臓脂肪蓄積抑制効果を発揮することが明らかとなった。 From the above results, alginic acid K (average molecular weight 210,000) is superior to alginic acid K (average molecular weight 52,000) in suppressing weight gain and visceral fat accumulation due to a high-fat diet, and body weight can be reduced in a shorter period of time. It has been clarified that it exhibits an increase suppressing effect and a visceral fat accumulation suppressing effect.
実施例４ アルギン酸カリウム（重量平均分子量約４１万）の抗肥満効果
（４−１ 試験試料）
試験試料として、実施例２で用いたものと同じアルギン酸Ｋ（平均分子量４１万）又はアルギン酸Ｋ（平均分子量５万）を用いた。
（４−２ 試験群）
試験群１〜４（各群Ｎ＝１２）は、以下の表５に記載の４つの試験食で実施した。試験食中のコーン油、ラード、カゼイン、セルロース、ＡＩＮ７６ミネラル混合、ＡＩＮ７６ビタミン混合、α化ポテト澱粉は、オリエンタル酵母工業（株）製、蔗糖は和光純薬（株）製スクロース細粒（特級）を使用した。
Example 4 Anti-obesity effect of potassium alginate (weight average molecular weight of about 410,000) (4-1 test sample)
As the test sample, the same alginic acid K (average molecular weight 410,000) or alginic acid K (average molecular weight 50,000) used in Example 2 was used.
(4-2 study group)
Test groups 1 to 4 (each group N = 12) were conducted with four test meals described in Table 5 below. Corn oil, lard, casein, cellulose, AIN76 mineral mixture, AIN76 vitamin mixture and pregelatinized potato starch in the test meal are manufactured by Oriental Yeast Co., Ltd., and sucrose is sucrose fine granules (special grade) manufactured by Wako Pure Chemical Industries, Ltd. It was used.
（４−３ 試験動物および飼育条件）
７週齢雄性マウスＣ５７ＢＬ／６Ｊ Ｊｃｌ（日本クレア）を１週間通常食（ＣＥ−２：ｍｏｉｓｔｕｒｅ ９．３％、ｃｒｕｄｅ ｐｒｏｔｅｉｎ ２５．１％、ｃｒｕｄｅ ｆａｔ ４．８％、ｃｒｕｄｅ ｆｉｂｅｒ ４．２％、ｃｒｕｄｅ ａｓｈ ６．７％、ＮＦＥ ５０．０％：日本クレア製）で飼育後、８週齢時に初期体重がほぼ一定になるように４つの試験群に群分けした。群分け後、表５に示した試験食を用いて試験を開始し、２週後まで試験を実施した。給餌はローデンカフェを用いた自由摂食、給水は自由飲水とした。
（４−４ 体重および内臓脂肪重量の測定）
体重測定は試験開始後、週１回測定した。試験最終日は解剖直前まで自由摂食、自由飲水とした。マウスをイソフルラン吸入麻酔下で開腹し、腹部大静脈より採血を行い安楽死させた。その後、内臓脂肪（副睾丸周囲脂肪、腎周囲脂肪、後腹膜脂肪、腸間膜脂肪）を採取し、重量を測定し、その合計値を内臓脂肪量とした。
（４−５ データ解析および統計学的検定法）
各測定について、平均±標準誤差（Ｓ．Ｅ．）を算出した。群間の統計学的有意差については、分散分析によって有意性（Ｐ＜０．０５）が認められた場合、多重比較検定（Ｆｉｓｈｅｒ’ｓ ＰＬＳＤ法）を実施した。
(4-3 Test animals and rearing conditions)
7-week-old male mouse C57BL / 6J Jcl (CLEA Japan) was fed for a week (CE-2: moisture 9.3%, crude protein 25.1%, crude fat 4.8%, crude fiber 4.2%, bred in crude ash 6.7%, NFE 50.0%: manufactured by CLEA Japan), and then grouped into 4 test groups so that the initial body weight was almost constant at 8 weeks of age. After grouping, the test was started using the test meal shown in Table 5, and the test was conducted until 2 weeks later. Feeding was free food using Roden Cafe, and water supply was free drinking.
(4-4 Measurement of body weight and visceral fat weight)
Body weight was measured once a week after the start of the test. On the last day of the test, the animals were allowed to eat and drink freely until immediately before dissection. Mice were laparotomized under isoflurane inhalation anesthesia, blood was collected from the abdominal vena cava and euthanized. Thereafter, visceral fat (peri-testicular periphery, perirenal fat, retroperitoneal fat, mesenteric fat) was collected and weighed, and the total value was taken as the visceral fat mass.
(4-5 Data analysis and statistical testing)
For each measurement, the mean ± standard error (SE) was calculated. For statistically significant differences between groups, a multiple comparison test (Fisher's PLSD method) was performed when significance (P <0.05) was found by analysis of variance.
（４−６ 結果）
（１）体重
試験前、試験開始２週後の体重を下表６に示した。試験開始２週後の体重の分散分析のＰ値は５％未満であった（Ｐ＜０．０５）。Ｆｉｓｈｅｒ’ｓ ＰＬＳＤ検定は、高脂肪食群（試験群２）と比較し、有意水準５％未満の場合にはＰ値、５％以上の場合にはＮ．Ｓ．（not significant）を表記した。
高脂肪食群（試験群２）は、低脂肪食群（試験群１）に比べて試験開始２週後の体重が有意に高く、高脂肪食摂取による肥満が認められた。アルギン酸Ｋ（平均分子量５万）摂取群（試験群３）の２週後の体重は高脂肪食群（試験群２）と有意な差がなく明確な肥満抑制効果は認められなかった。一方、アルギン酸Ｋ（平均分子量４１万）摂取群（試験群４）では、２週後の体重が高脂肪食群（試験群２）に比べて有意に低く、肥満抑制効果が認められた。
(4-6 results)
(1) Body weight Table 6 shows the body weight before the test and 2 weeks after the start of the test. The P value of body weight analysis of variance 2 weeks after the start of the study was less than 5% (P <0.05). The Fisher's PLSD test is compared with the high fat diet group (Test Group 2), and the P value is 5% or more when the significance level is less than 5%. S. (Not significant) is shown.
The high fat diet group (Test Group 2) had significantly higher body weight 2 weeks after the start of the test than the low fat diet group (Test Group 1), and obesity due to the intake of a high fat diet was observed. The body weight after 2 weeks of the alginic acid K (average molecular weight 50,000) ingestion group (test group 3) was not significantly different from the high fat diet group (test group 2), and no clear obesity suppressing effect was observed. On the other hand, in the alginic acid K (average molecular weight 410,000) ingestion group (test group 4), the body weight after 2 weeks was significantly lower than in the high fat diet group (test group 2), and an obesity suppressing effect was observed.
（２）内臓脂肪量
各群の試験開始２週後の内臓脂肪量を上表７に示した。内臓脂肪量の分散分析のＰ値は５％未満（Ｐ＜０．０００１）であった。Ｆｉｓｈｅｒ’ｓ ＰＬＳＤ検定は、高脂肪食群（試験群２）またはアルギン酸Ｋ（平均分子量５万）（試験群３）と比較し有意水準５％未満の場合にはＰ値、５％以上の場合にはＮ．Ｓ．（not significant）を表記した。
高脂肪食群（試験群２）は、低脂肪食群（試験群１）に比べて内臓脂肪量が有意に多く、高脂肪食摂取による内臓脂肪蓄積が確認された。アルギン酸Ｋ（平均分子量５万）摂取群（試験群３）の内臓脂肪量は高脂肪食群（試験群２）より少なく、内臓脂肪蓄積抑制作用が認められた。一方、アルギン酸Ｋ（平均分子量４１万）摂取群（試験群４）の内臓脂肪重は高脂肪食群（試験群２）に比べて有意に少なく、さらに、アルギン酸Ｋ（平均分子量５万）に比べ有意に少なかった。
(2) Visceral fat mass The visceral fat mass of each group 2 weeks after the start of the test is shown in Table 7 above. The P value of the analysis of variance for visceral fat mass was less than 5% (P <0.0001). The Fisher's PLSD test is used when the P value is 5% or more when the significance level is less than 5% compared to the high fat diet group (test group 2) or alginic acid K (average molecular weight 50,000) (test group 3). N. S. (Not significant) is shown.
The high-fat diet group (Test Group 2) had a significantly higher amount of visceral fat than the low-fat diet group (Test Group 1), and the visceral fat accumulation due to the intake of the high-fat diet was confirmed. The visceral fat amount of the alginic acid K (average molecular weight 50,000) intake group (test group 3) was smaller than that of the high fat diet group (test group 2), and the visceral fat accumulation inhibitory action was observed. On the other hand, the visceral fat weight of the alginic acid K (average molecular weight 410,000) intake group (test group 4) is significantly smaller than that of the high-fat diet group (test group 2), and further compared to alginic acid K (average molecular weight 50,000). Significantly less.
以上の結果から、アルギン酸Ｋ（平均分子量４１万）は、アルギン酸Ｋ（平均分子量５万）に比べて高脂肪食による体重増加や内臓脂肪蓄積を抑制する作用に優れ、より短期間で体重増加抑制効果や内臓脂肪蓄積抑制効果を発揮することが明らかとなった。 From the above results, alginic acid K (average molecular weight 410,000) is superior to alginic acid K (average molecular weight 50,000) in suppressing weight gain and visceral fat accumulation due to a high-fat diet and suppressing weight gain in a shorter period of time. It became clear that the effect and the visceral fat accumulation suppression effect were exhibited.
以上、本発明の実施形態を説明したが、これが、本発明を、説明した特定の実施形態に限定することを意図するものではないことを理解すべきである。本発明の範囲内にある様々な他の変更及び修正は当業者には明白である。
本明細書に引用されている文献及び特許出願は、あたかもそれが本明細書に完全に記載されているかのように参考として援用される。
While embodiments of the present invention have been described above, it should be understood that this is not intended to limit the invention to the particular embodiments described. Various other changes and modifications within the scope of the invention will be apparent to those skilled in the art.
Documents and patent applications cited herein are incorporated by reference as if they were fully described herein.
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