JP2016196450A - Agent for inhibiting rise in blood glucose, comprising indigestible glucan, and use therefor - Google Patents
Agent for inhibiting rise in blood glucose, comprising indigestible glucan, and use therefor Download PDFInfo
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- JP2016196450A JP2016196450A JP2016052506A JP2016052506A JP2016196450A JP 2016196450 A JP2016196450 A JP 2016196450A JP 2016052506 A JP2016052506 A JP 2016052506A JP 2016052506 A JP2016052506 A JP 2016052506A JP 2016196450 A JP2016196450 A JP 2016196450A
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Abstract
Description
本発明は、難消化性グルカンを有効成分とする血糖上昇抑制剤およびその用途に関する。 The present invention relates to a blood sugar elevation inhibitor comprising an indigestible glucan as an active ingredient and use thereof.
糖尿病、特に食べ過ぎ、飲み過ぎ、運動不足等の生活習慣が原因となる2型糖尿病の増加が近年大きな社会問題となっている。厚生労働省による平成19年の国民栄養・健康調査の結果では、日本国内には、「糖尿病が強く疑われる人」が890万人、「糖尿病の可能性を否定できない人」が1320万人と計2000万人以上の糖尿病が疑われる人がいると推定されている。糖尿病は、放置すると糖尿病神経障害、糖尿病網膜症、糖尿病腎症等の重篤な合併症を併発する非常に危険な病気である。
In recent years, an increase in
これまで、糖尿病の治療・予防を目的とした種々の血糖上昇抑制作用を有する化合物あるいは組成物が提案されており、例えば、茶ポリフェノール(特許文献1)、金耳から分離される酸性ヘテロ多糖(特許文献2)、加熱処理したアラビアガム(特許文献3)、焙焼デキストリンの酸加水分解物(特許文献4)、特殊な多分岐構造を有するα-グルカン(特許文献5)、発芽玄米糠由来のステロール配糖体(特許文献6)、キサンタンガムおよび水溶性カルシウム塩・クエン酸塩(特許文献7)、マツ科モミ属植物の樹葉の抽出物(特許文献8)などが血糖上昇抑制剤としての機能を有することが報告されている(特許文献1〜8 )。しかしながら、いずれの素材も特定の原料から抽出精製作業が必要であったり加工処理が必要であったり、製造に特殊な酵素が必要であったりと、供給安定性や製造コストの点で問題があった。さらに、血糖上昇抑制剤の選択肢を広げる意味でも、新たな素材の開発が望まれていた。 So far, various compounds or compositions having an inhibitory effect on the increase in blood glucose for the purpose of treatment / prevention of diabetes have been proposed. For example, tea polyphenol (Patent Document 1), acidic heteropolysaccharide isolated from gold ears ( Patent document 2), heat-treated gum arabic (patent document 3), acid hydrolyzate of roasted dextrin (patent document 4), α-glucan having a special multi-branched structure (patent document 5), derived from germinated brown rice bran Sterol glycosides (Patent Document 6), xanthan gum and water-soluble calcium salt / citrate (Patent Document 7), extracts of Pinus fir plants (Patent Document 8), etc. It has been reported that it has a function (patent documents 1 to 8). However, each material has problems in terms of supply stability and manufacturing cost, such as extraction and purification from specific raw materials, processing, and the need for special enzymes for production. It was. Furthermore, the development of a new material has been desired also in the sense of expanding the options for blood sugar elevation inhibitors.
一方、特許文献9には、活性炭を触媒として原料糖質を加熱することを特徴とする糖縮合物(水溶性食物繊維)の製造方法が開示されている。当該製法により、DE70〜100の澱粉分解物を加熱縮合することで簡便・安価な製法で新たな水溶性食物繊維素材が製造されている。しかしながら、特許文献9には、この水溶性食物繊維素材の血糖上昇抑制作用については一切開示されていない。
On the other hand,
本発明は、新たな血糖上昇抑制剤を提供することを目的とする。 An object of the present invention is to provide a new blood sugar elevation inhibitor.
本願発明者らは、DE70〜100の澱粉分解物を加熱縮合させて得られた糖縮合物からなる難消化性グルカンが生体内で血糖上昇抑制作用を有することを見出した。本発明はこの知見に基づくものである。
すなわち、本発明は以下の通りである。
(1) DE70〜100の澱粉分解物を加熱縮合させて得られた糖縮合物からなる難消化性グルカンまたは該難消化性グルカン処理物を含んでなる、血糖上昇抑制剤。
(2) 難消化性グルカンが、活性炭の存在下で加熱縮合させて得られた糖縮合物からなる、(1)に記載の血糖上昇抑制剤。
(3) 難消化性グルカンが、100〜300℃で加熱縮合させて得られた糖縮合物からなる、(1)または(2)に記載の血糖上昇抑制剤。
(4) (1)〜(3)のいずれか一項記載の血糖上昇抑制剤を含有する医薬品、医薬部外品、飲食品、または飼料。
The inventors of the present application have found that an indigestible glucan composed of a sugar condensate obtained by heat condensation of a starch degradation product of
That is, the present invention is as follows.
(1) A hyperglycemic inhibitor comprising an indigestible glucan comprising a sugar condensate obtained by heat condensation of a starch degradation product of
(2) The antihyperglycemic agent according to (1), wherein the indigestible glucan comprises a sugar condensate obtained by heat condensation in the presence of activated carbon.
(3) The antihyperglycemic agent according to (1) or (2), wherein the indigestible glucan comprises a sugar condensate obtained by heat condensation at 100 to 300 ° C.
(4) A pharmaceutical, a quasi-drug, a food or drink, or a feed containing the blood sugar elevation inhibitor according to any one of (1) to (3).
本発明によれば、難消化性グルカンを使用することで、安価で安定的に供給可能な新規の血糖上昇抑制剤を提供できる点で有利である。 According to the present invention, the use of an indigestible glucan is advantageous in that it can provide a novel antihyperglycemic agent that can be stably supplied at low cost.
本発明による血糖上昇抑制剤は、DE70〜100の澱粉分解物を加熱縮合させて得られた糖縮合物からなる難消化性グルカンまたは該難消化性グルカン処理物を含んでなる血糖上昇抑制剤である。
The antihyperglycemic agent according to the present invention is an antihyperglycemic agent comprising an indigestible glucan comprising a sugar condensate obtained by heat condensation of a starch degradation product of
本発明において「難消化性グルカン」は、難消化性のグルカン(グルコースポリマー)を意味し、DE70〜100の澱粉分解物を、加熱処理により縮合反応させることで得られる糖縮合物として得ることができる。すなわち、本発明における難消化性グルカンは、DE70〜100の澱粉分解物の加熱縮合物である。難消化性グルカンは、水溶性食物繊維画分を豊富に有している。
In the present invention, “indigestible glucan” means an indigestible glucan (glucose polymer), and can be obtained as a sugar condensate obtained by subjecting a starch degradation product of
難消化性グルカンの原料となる澱粉分解物としては、DEが70〜100である澱粉分解物を使用することができる。澱粉分解物のDEが70を下回ると、分解が不十分であるために得られる難消化性グルカンに澱粉由来の構造が多く残存してしまい、体内酵素により分解され易く容易に吸収されてしまう傾向があり、血糖上昇抑制作用の点で好ましくない。ここで、「DE(Dextrose Equivalent)」とは、澱粉分解物の分解度合いの指標であり、試料中の還元糖をブドウ糖として固形分に対する百分率で示した値である。澱粉分解物は、DEが75〜100であることが好ましく、80〜100であることがより好ましい。本発明に用いられる「DE70〜100の澱粉分解物」は、DEが所定の範囲を満たす澱粉分解物であればよく、例えば、マルトオリゴ糖、水飴、粉飴、グルコース等が挙げられる。その性状も特に制限はなく、結晶品(無水ぶどう糖結晶、含水ぶどう糖結晶等)、液状品(液状ぶどう糖、水飴等)、非結晶粉末品(粉飴等)のいずれでも良いが、ハンドリングや製造コストを考慮すると液状品を用いることが好ましい。特に、グルコースの精製工程で生じる副産物である「ハイドロール」と呼ばれるグルコースシラップの使用は、リサイクルや原料コスト削減の観点から極めて有利である。
As a starch degradation product that is a raw material for the indigestible glucan, a starch degradation product having a DE of 70 to 100 can be used. When the DE of the starch degradation product is less than 70, the decomposition is insufficient, and thus the structure derived from starch remains in the indigestible glucan obtained and tends to be easily decomposed by the enzyme in the body and easily absorbed. This is not preferable from the viewpoint of an inhibitory effect on blood sugar elevation. Here, “DE (Dextrose Equivalent)” is an index of the degree of degradation of the starch degradation product, and is a value expressed as a percentage of the solid content with the reducing sugar in the sample as glucose. The starch degradation product preferably has a DE of 75 to 100, more preferably 80 to 100. The “degraded starch of
本発明において「加熱縮合」は、澱粉分解物を加熱条件下において縮合させることをいい、加熱縮合方法は当業者に周知である。加熱縮合における加熱条件は、縮合反応により水溶性食物繊維が豊富な難消化性グルカン(糖縮合物)が得られれば特に制限はなく、当業者であれば加熱条件を適宜決定することができるが、得られる難消化性グルカン(糖縮合物)の食物繊維含量が70%以上となるように加熱することが好ましく、例えば、100℃〜300℃で1〜180分間、より好ましくは、150℃〜250℃で1〜180分間加熱処理することで製造できる。 In the present invention, “heat condensation” refers to condensation of a starch decomposition product under heating conditions, and the heat condensation method is well known to those skilled in the art. The heating conditions in the heat condensation are not particularly limited as long as an indigestible glucan (sugar condensate) rich in water-soluble dietary fiber is obtained by the condensation reaction, and those skilled in the art can appropriately determine the heating conditions. It is preferable to heat the resulting indigestible glucan (sugar condensate) so that the dietary fiber content is 70% or more, for example, 100 ° C. to 300 ° C. for 1 to 180 minutes, more preferably 150 ° C. to It can manufacture by heat-processing at 250 degreeC for 1-180 minutes.
本発明において「加熱縮合」は、無触媒条件下で行ってもよいが、縮合反応の反応効率の点から触媒存在下で行うことが好ましい。前記触媒としては糖縮合反応を触媒するものであれば特に制限はないが、無機酸(塩酸、リン酸、硫酸、硝酸等)、有機酸(クエン酸、フマル酸、酒石酸、コハク酸、酢酸等)、鉱物性物質(珪藻土、活性白土、酸性白土、ベントナイト、カオリナイト、タルク等)および活性炭(水蒸気炭、塩化亜鉛炭、スルホン化活性炭、酸化活性炭等)を用いることができる。得られる水溶性食物繊維素材の着色や安全性、更には味・臭いを考慮すると、触媒として活性炭を用いることが好ましい。また、前記各触媒は2種以上を組み合わせて使用することもできる。 In the present invention, “heat condensation” may be performed under non-catalytic conditions, but is preferably performed in the presence of a catalyst from the viewpoint of the reaction efficiency of the condensation reaction. The catalyst is not particularly limited as long as it catalyzes a sugar condensation reaction, but inorganic acids (hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, etc.), organic acids (citric acid, fumaric acid, tartaric acid, succinic acid, acetic acid, etc.) ), Mineral substances (diatomaceous earth, activated clay, acid clay, bentonite, kaolinite, talc, etc.) and activated carbon (steam coal, zinc chloride charcoal, sulfonated activated carbon, oxidized activated carbon, etc.) can be used. In consideration of coloring and safety of the resulting water-soluble dietary fiber material, as well as taste and odor, it is preferable to use activated carbon as a catalyst. Moreover, each said catalyst can also be used in combination of 2 or more type.
本発明に用いる難消化性グルカンは、上記手法で得られた糖縮合物をそのまま用いても良く、あるいは、難消化性グルカンの各種処理物を用いても良い。難消化性グルカン処理物としては、例えば、難消化性グルカン酵素処理物、難消化性グルカン分画処理物、難消化性グルカン還元処理物が挙げられる。難消化性グルカン処理物は、複数の処理を組合わせたものでも良い。 As the indigestible glucan used in the present invention, the sugar condensate obtained by the above method may be used as it is, or various processed products of indigestible glucan may be used. Examples of the indigestible glucan-treated product include an indigestible glucan enzyme-treated product, an indigestible glucan fraction-treated product, and an indigestible glucan reduction-treated product. The indigestible glucan-treated product may be a combination of a plurality of treatments.
本発明において「難消化性グルカン酵素処理物」は、糖縮合物を糖質分解酵素で酵素処理して得ることができる。当該処理により難消化性グルカン中の消化性部位を分解することができる。 In the present invention, the “indigestible glucan enzyme-treated product” can be obtained by enzymatic treatment of a sugar condensate with a saccharide-degrading enzyme. The digestible site in the indigestible glucan can be decomposed by the treatment.
本発明に用いられる「糖質分解酵素」は、糖質に作用し加水分解反応を触媒する酵素であり、特に制限はないが、例えば、α−アミラーゼ、β−アミラーゼ、グルコアミラーゼ(アミログルコシダーゼ)、イソアミラーゼ、プルラナーゼ、α−グルコシダーゼ、シクロデキストリングルカノトランスフェラーゼ、β−グルコシダーゼ、β−ガラクトシダーゼ、β−マンノシダーゼ、β−フルクトシダーゼ、セロビアーゼ、ゲンチオビアーゼ等を挙げることができ、前記酵素を単独で用いてもよく、複数の酵素を組み合わせて用いてもよい。難消化性グルカンへの分解作用からα−アミラーゼ、グルコアミラーゼが好ましく、両酵素のいずれかを単独で作用させてもよいが、α−アミラーゼおよびグルコアミラーゼを共に作用させるのが特に好ましい。 The “carbohydrase” used in the present invention is an enzyme that acts on a carbohydrate and catalyzes a hydrolysis reaction, and is not particularly limited. For example, α-amylase, β-amylase, glucoamylase (amyloglucosidase) is used. , Isoamylase, pullulanase, α-glucosidase, cyclodextrin glucanotransferase, β-glucosidase, β-galactosidase, β-mannosidase, β-fructosidase, cellobiase, gentiobiase, etc. Alternatively, a plurality of enzymes may be used in combination. Α-Amylase and glucoamylase are preferred from the action of degrading into indigestible glucan, and either of these enzymes may be allowed to act alone, but it is particularly preferred that α-amylase and glucoamylase are allowed to act together.
本発明において「酵素処理」の処理条件は、酵素処理により糖縮合物の易消化性部分が消化される条件であれば特に制限はなく、当業者であれば酵素処理条件を適宜決定することができるが、酵素処理によりグルコース含量が1%以上、より好ましくは2%以上増加するように処理するのが好ましく、例えば、20〜120℃で30分間〜48時間、より好ましくは、50〜100℃で30分間〜48時間酵素処理することができる。 In the present invention, the treatment conditions for the “enzyme treatment” are not particularly limited as long as the digestible portion of the sugar condensate is digested by the enzyme treatment, and those skilled in the art can appropriately determine the enzyme treatment conditions. However, it is preferable that the glucose content is increased by 1% or more, more preferably 2% or more by enzyme treatment, for example, 20 to 120 ° C. for 30 minutes to 48 hours, more preferably 50 to 100 ° C. For 30 minutes to 48 hours.
本発明において「難消化性グルカン分画処理物」は、難消化性グルカン酵素処理物を二糖以下の画分が15%以下となるように分画処理して得ることができる。言い換えれば「難消化性グルカン分画処理物」は三糖以上の糖類を85%を超えて有するものである。ここで「%」は、固形分に対する質量%を意味する。 In the present invention, the “indigestible glucan fraction-treated product” can be obtained by fractionating the indigestible glucan enzyme-treated product so that the fraction of disaccharide or less is 15% or less. In other words, the “digestible glucan fraction-treated product” has more than 85% of saccharides of three or more sugars. Here, “%” means mass% with respect to the solid content.
本発明において「分画処理」は、二糖以下の画分を15%以下にすることができるものであれば特に制限はなく、その分離方法は当業者に周知の手段を利用することができる。
前記分画処理は、例えば、膜分離、ゲルろ過クロマトグラフィー、カーボン−セライトカラムクロマトグラフィー、強酸性陽イオン交換カラムクロマトグラフィー、エタノール沈殿、溶媒沈殿など当業者に周知の糖質の精製方法を使用することができる。前記分画処理は、二糖以下の画分が10%以下となるよう行うのが好ましく、5%以下となることが特に好ましい。
In the present invention, the “fractionation treatment” is not particularly limited as long as the fraction less than or equal to the disaccharide can be reduced to 15% or less, and the separation method can use means well known to those skilled in the art. .
The fractionation treatment uses, for example, carbohydrate purification methods well known to those skilled in the art, such as membrane separation, gel filtration chromatography, carbon-celite column chromatography, strong acid cation exchange column chromatography, ethanol precipitation, and solvent precipitation. can do. The fractionation treatment is preferably performed so that the fraction of disaccharides or less is 10% or less, and particularly preferably 5% or less.
本発明において「難消化性グルカン還元処理物」は、難消化性グルカンを還元処理して得ることができる。本発明において「還元処理」は、糖の還元末端のグルコシル基のアルデヒド基を水酸基に還元する処理をいう。還元処理方法は当業者に周知であり、例えば、ヒドリド還元剤を用いる方法、プロトン性溶媒中の金属を用いる方法、電解還元方法、接触水素化反応方法等が挙げられる。本発明においては、少量の糖アルコールを調製する場合にはヒドリド還元剤を用いる方法が簡便且つ特殊な装置を必要とせず便利であり、一方で、工業的に大規模に実施する場合には、経済性に優れ、副生成物も少ないという点から、接触水素化反応を用いる方法が好ましい。「接触水素化反応」とは、触媒の存在下、不飽和有機化合物の二重結合部に水素を添加する反応であり、一般に水添反応とも言われている。 In the present invention, the “reduced product of indigestible glucan” can be obtained by reducing the indigestible glucan. In the present invention, “reduction treatment” refers to treatment for reducing the aldehyde group of the glucosyl group at the reducing end of a sugar to a hydroxyl group. The reduction treatment method is well known to those skilled in the art, and examples thereof include a method using a hydride reducing agent, a method using a metal in a protic solvent, an electrolytic reduction method, and a catalytic hydrogenation reaction method. In the present invention, when preparing a small amount of sugar alcohol, the method using a hydride reducing agent is convenient and convenient without requiring a special device, while on the other hand, when carried out industrially on a large scale, A method using a catalytic hydrogenation reaction is preferable because it is economical and has few by-products. The “catalytic hydrogenation reaction” is a reaction in which hydrogen is added to a double bond portion of an unsaturated organic compound in the presence of a catalyst, and is generally also referred to as a hydrogenation reaction.
本発明における「還元処理」を具体的に説明すると、難消化性グルカンを水に溶解し、そこにラネーニッケル触媒を適量加え、水素ガスを添加し、高温条件下で還元する。次に、脱色・脱イオン処理して、難消化性グルカン還元処理物を得ることができる。 The “reduction treatment” in the present invention will be specifically described. Indigestible glucan is dissolved in water, an appropriate amount of Raney nickel catalyst is added thereto, hydrogen gas is added, and reduction is performed under high temperature conditions. Next, decolorization and deionization treatment can be performed to obtain an indigestible glucan reduction treatment product.
本発明による血糖上昇抑制剤は、上記手法等を用いて、DE70〜100の澱粉分解物を、加熱処理により縮合反応させる製造方法で得ることができる。本発明において「血糖上昇抑制剤」とは、糖質を含有する食品の摂取時・摂取後における、糖質の消化吸収に伴う血糖値の上昇を抑制する製剤を意味する。本発明の血糖上昇抑制剤は、糖尿病、特に2型糖尿病の予防や治療用に用いることができる。更に、糖尿病合併症、生活習慣病、メタボリックシンドローム(内臓脂肪症候群)、動脈硬化等の疾病の予防や治療用に用いることができる。
The blood sugar elevation inhibitor according to the present invention can be obtained by a production method in which the starch degradation product of
本発明による血糖上昇抑制剤は、難消化性グルカンを含有していればよく、難消化性グルカン単独でも、その他の成分と混合したものであっても良い。例えば、茶ポリフェノール、加熱処理アラビアガム、焙焼デキストリン酸加水分解物等の公知の血糖上昇抑制剤や他の薬理作用を有する物質と混合したものであっても良い。 The blood sugar elevation inhibitor according to the present invention only needs to contain indigestible glucan, and may be indigestible glucan alone or mixed with other components. For example, it may be a mixture with a known blood sugar elevation inhibitor such as tea polyphenol, heat-treated gum arabic, or roasted dextrin acid hydrolyzate or other substances having pharmacological action.
本発明による血糖上昇抑制剤は、必要に応じて、有効成分である難消化性グルカンに対し薬学的に許容される基材や担体を添加して製剤化することができる。本発明による血糖上昇抑制剤は、例えば、経口投与される製剤であり、錠剤、顆粒剤、散剤、液剤、粉末、顆粒、カプセル剤等の形態で提供することができる。このような製剤化は、通常、医薬の製造に用いられる方法に従って、製造することができる。本発明によれば、本発明による血糖上昇抑制剤を医薬品または医薬部外品に含有させて使用することができる。 The blood sugar elevation inhibitor according to the present invention can be formulated by adding a pharmaceutically acceptable base material or carrier to an indigestible glucan that is an active ingredient, if necessary. The antihyperglycemic agent according to the present invention is, for example, a preparation to be administered orally, and can be provided in the form of tablets, granules, powders, solutions, powders, granules, capsules and the like. Such a formulation can be usually produced according to a method used for producing a medicine. According to the present invention, the antihyperglycemic agent according to the present invention can be used by being contained in a pharmaceutical or a quasi-drug.
本発明の血糖上昇抑制剤は、また、飲食品に含有させて提供することもできる。すわなち、難消化性グルカンまたはその処理物を含有する血糖上昇抑制用飲食品を提供することもできる。添加する飲食品の種類に特に制限はなく、例えば、日常的に食する飲食品、健康食品(特定保健用食品、栄養機能食品、栄養補助食品等)、機能性食品、病者用食品等として提供することができる。その形態としては、飲食物、錠剤、液剤、カプセル(軟カプセル、硬カプセル)、粉末、顆粒、スティック、ゼリーなどが挙げられる。このような飲食品は、通常、食品の製造に用いられる方法に従って、製造することができる。なお、「特定保健用食品」とは、機能等を表示して食品の製造または販売等を行う場合に、保健上の観点から法上の何らかの制限を受けることがある食品をいう。 The blood sugar elevation inhibitor of the present invention can also be provided by being contained in food or drink. That is, it is also possible to provide a food / beverage product for suppressing an increase in blood glucose containing an indigestible glucan or a processed product thereof. There are no particular restrictions on the types of foods and drinks to be added, such as foods and drinks to be eaten on a daily basis, health foods (food for specified health use, nutritional functional foods, nutritional supplements, etc.), functional foods, foods for the sick, etc. Can be provided. Examples of the form include foods and drinks, tablets, liquids, capsules (soft capsules, hard capsules), powders, granules, sticks, jelly, and the like. Such foods and drinks can usually be produced according to the methods used for producing foods. The “special health food” refers to a food that may be subject to some legal restrictions from the viewpoint of health when the function or the like is displayed to manufacture or sell the food.
更に、本発明の血糖上昇抑制剤は、飼育・養殖動物(家畜、家禽、魚類等)やペット・愛玩動物の飼料に含有させて使用することもできる。 Furthermore, the blood sugar elevation inhibitor of the present invention can be used by being contained in feeds for breeding / cultured animals (livestock, poultry, fish, etc.) and pets / competent animals.
本発明による血糖上昇抑制剤の使用量は、特に制限されず、適宜設定することができる。例えば、難消化性グルカンまたはその処理物が、食物繊維量として、1日あたり1〜30g、好ましくは、1〜10g摂取されるように設定することができる。 The usage-amount of the blood sugar elevation inhibitor by this invention is not restrict | limited in particular, It can set suitably. For example, the indigestible glucan or the processed product thereof can be set so that the amount of dietary fiber is ingested 1 to 30 g, preferably 1 to 10 g per day.
本発明によれば、DE70〜100の澱粉分解物を加熱縮合させて得られた糖縮合物からなる難消化性グルカンまたは該難消化性グルカン処理物を血糖上昇抑制剤として含有する医薬品、医薬部外品、飲食品および飼料が提供される。難消化性グルカンまたは該難消化性グルカン処理物の含有量も特に制限はなく製品形態によりその含有量も様々であるが、例えば医薬品に含有させる場合は1〜20質量%、医薬部外品に含有させる場合は1〜20質量%、飲食品に含有させる場合は0.5〜10質量%、飼料に含有させる場合は1〜20質量%とすることができる。 ADVANTAGE OF THE INVENTION According to this invention, the pharmaceutical which contains the indigestible glucan which consists of a sugar condensate obtained by heat-condensing the starch degradation product of DE70-100, or this indigestible glucan processed product as a blood glucose rise inhibitor as a blood sugar rise inhibitor Foreign goods, food and drink, and feed are provided. The content of the indigestible glucan or the processed material of the indigestible glucan is not particularly limited, and the content varies depending on the product form. For example, when it is contained in a pharmaceutical product, it is 1 to 20% by mass. When it is contained, it can be 1 to 20% by mass, when it is contained in food or drink, it can be 0.5 to 10% by mass, and when it is contained in feed, it can be 1 to 20% by mass.
以下の例に基づいて本発明を具体的に説明するが、本発明はこれらの例に限定されるものではない。
実施例:難消化性グルカンの血糖上昇抑制作用の確認試験
The present invention will be specifically described based on the following examples, but the present invention is not limited to these examples.
Example: Confirmation test of blood glucose elevation inhibitory effect of indigestible glucan
〔確認試験1〕[Confirmation test 1]
試験食品
試験食品の処方を表1に示した。
Table 1 shows the formulation of the test food test food.
試験食品の栄養成分を表2に示した。 Table 2 shows the nutritional components of the test food.
難消化性グルカンとしては、フィットファイバー#80(日本食品化工株式会社製)をα-アミラーゼ及びグルコアミラーゼによる酵素処理の後、脱色・精製・濃縮・樹脂分画・乾燥して得られた粉末を使用した。フィットファイバー#80は、DE87(レーンエイノン法で測定)の澱粉分解物を、特開2013−76044号に記載の方法に従って、活性炭を触媒として加熱縮合させることで得られる糖縮合物である。
As an indigestible glucan, a powder obtained by decolorizing, purifying, concentrating, fractionating resin, and drying Fit Fiber # 80 (manufactured by Nippon Shokuhin Kako Co., Ltd.) with α-amylase and glucoamylase, used.
マルトデキストリンとしては、パインデックス#2(松谷化学工業株式会社製)を使用した。なお、マルトデキストリンは、難消化性グルカンと同等の着色となるように着色料(カラメル)を用いて色調を調整した。 As the maltodextrin, Paindex # 2 (manufactured by Matsutani Chemical Industry Co., Ltd.) was used. In addition, the color tone of maltodextrin was adjusted using a coloring agent (caramel) so that it might become the same color as indigestible glucan.
被験者の選択基準
被験者は、下記の選択基準に該当する者を対象とした。
1) 20歳以上、65歳未満の男女
2) スクリーニング検査の結果、試験責任医師が糖尿病境界域者(1:空腹時血糖値110mg/dL以上125mg/dL以下、2:ブドウ糖負荷試験(トレーランG75g負荷)2時間値が140mg/dL以上199mg/dL以下、3:随時血糖値140mg/dL以上199mg/dL以下のいずれかに該当)と判断した者
3) アルコール多量常飲者でない者(スクリーニング検査、各負荷試験実施2日前からの禁酒が可能な者)
4) 試験の目的・内容について十分な説明を受け、同意能力があり、よく理解した上で自発的に参加を志願し、書面で試験参加に同意した者
Selection criteria for subjects The subjects were those who met the following selection criteria.
1) Males and
4) A person who has received sufficient explanation about the purpose and content of the exam, has the ability to consent, has voluntarily understood and volunteered to participate, and has agreed to participate in the exam in writing.
試験のデザイン
試験は、先ず被験者に対して2週間の前観察を行った。その後、負荷試験前夜の夕食の摂取から負荷試験開始まで12時間以上空け、負荷試験を行った。被験者数は非投与群23名、投与群23名で行った。
Study design In the study, subjects were first observed for 2 weeks prior. After that, the load test was performed after 12 hours or more from the ingestion of dinner the night before the load test to the start of the load test. The number of subjects was 23 in the non-administration group and 23 in the administration group.
なお、試験食品は、1包を100mlの水に溶かしたものを、負荷食(市販のおにぎり(米飯300g))と水200mlと同時に10分以内に残さず摂取し、試験食品摂取後に沈殿があったら再度水を注いですべて摂取した。 As for the test food, one package dissolved in 100 ml of water was consumed within 10 minutes simultaneously with the load meal (commercial rice ball (300 g of cooked rice)) and 200 ml of water, and precipitation occurred after ingestion of the test food. Then I poured water again and ingested everything.
検査及び調査
負荷試験に各項目を測定し、検査数値を比較して有効性を確認した。
1.血糖値の経時的変化
2.インスリン値の経時的変化
3.血糖値のAUC(血中濃度曲線下面積)
Inspection and investigation Each item was measured in the load test, and the effectiveness was confirmed by comparing the inspection values.
1. 1. Change in blood glucose level over
有効性に関する解析
血糖値の経時的変化、インスリン値の経時的変化に関し、下記手順で比較した。
1) 検査数値から負荷食摂取前の数値を減じて変化量(Δ血糖値およびΔインスリン値)を算出し、基本統計量(平均値、標準誤差)を解析する。
2) 負荷食摂取前、摂取後30、60、90、120分について非投与群と投与群の値をDunnett検定により比較する。
Analysis on effectiveness The changes in blood glucose level and insulin level with time were compared by the following procedure.
1) Subtract the numerical value before ingesting the loaded food from the test value to calculate the amount of change (Δ blood glucose level and Δ insulin value), and analyze the basic statistics (average value, standard error).
2) The values of the non-administered group and the administered group are compared by Dunnett test before and after loading, 30, 60, 90, and 120 minutes after ingestion.
血糖値のAUCに関し、下記手順で比較した。
1) 検査数値を基に上記手順で算出した血糖値変化量(Δ血糖値)からTrapezoidal method(台形法)により血糖値変化量のAUC(Δ血糖値AUC)を算出する。
2) 基本統計量(平均値、標準誤差)を算出する。
3) Δ血糖値AUCについて非投与群と投与群の値をDunnett検定により比較する。
The AUC of blood glucose level was compared by the following procedure.
1) From the blood glucose level change amount (Δ blood glucose level) calculated in the above procedure based on the test value, the AUC of the blood glucose level change amount (Δ blood glucose level AUC) is calculated by the trapezoidal method (trapezoidal method).
2) Calculate basic statistics (mean value, standard error).
3) With respect to the Δ blood glucose level AUC, the values of the non-administered group and the administered group are compared by the Dunnett test.
試験結果
血糖値変化量の経時的変化、インスリン値変化量の経時的変化について解析を行い、非投与群と投与群の変化量をそれぞれ図1および図2に示した。
Test Results Analysis was performed on changes in blood glucose level change over time and changes in insulin level change over time, and the change amounts in the non-administered group and the administration group are shown in FIGS. 1 and 2, respectively.
血糖値変化量(Δ血糖値)において、非投与群と比較して、摂取後60分に有意に低い値を示した(Dunnett検定: p = 0.003)。インスリン値変化量(Δインスリン値)において、有意差はなかったが、摂取後60、90、120分で低い値を示した。 The blood glucose level change amount (Δ blood glucose level) was significantly lower than that of the non-administered group at 60 minutes after ingestion (Dunnett test: p = 0.003). There was no significant difference in the amount of change in insulin value (Δ insulin value), but it showed a low value at 60, 90, and 120 minutes after ingestion.
血糖値変化量のAUC(Δ血糖値AUC)について解析を行い、非投与群と投与群のΔ血糖値AUCを図3に示した。 The AUC of the blood glucose level change amount (Δ blood glucose level AUC) was analyzed, and the Δ blood glucose level AUC of the non-administered group and the administered group are shown in FIG.
Δ血糖値AUCにおいて、非投与群と比較して、投与群は有意に低い値を示した(Dunnett検定: p = 0.040)。 In the Δ blood glucose level AUC, the administration group showed a significantly lower value compared to the non-administration group (Dunnett test: p = 0.040).
本試験により、本発明における難消化性グルカンはΔ血糖値、Δ血糖値AUCについて、非投与群と比較して投与群で有意に低い値を示した。Δインスリン値において、有意差はなかったが、摂取後60、90、120分で低い値が確認された。なお、その他の条件が有効性の判定に影響を与えていないことは被験者の記録から確認されている。 According to this test, the indigestible glucan in the present invention showed significantly lower values in the administration group compared to the non-administration group for the Δ blood glucose level and the Δ blood glucose level AUC. There was no significant difference in Δinsulin level, but low values were confirmed at 60, 90, and 120 minutes after ingestion. It is confirmed from the subject's records that other conditions do not affect the determination of effectiveness.
〔確認試験2〕[Confirmation test 2]
試験食品
試験食品の処方を表3に示した。
Table 3 shows the formulations of the test food test food.
試験食品の栄養成分を表4に示した。 Table 4 shows the nutritional components of the test food.
難消化性グルカンとしては、フィットファイバー#80(日本食品化工株式会社製)をα-アミラーゼ及びグルコアミラーゼによる酵素処理の後、脱色・精製・濃縮・樹脂分画・乾燥して得られた粉末を使用した。フィットファイバー#80は、DE87(レーンエイノン法で測定)の澱粉分解物を、特開2013−76044号に記載の方法に従って、活性炭を触媒として加熱縮合させることで得られる糖縮合物である。
As an indigestible glucan, a powder obtained by decolorizing, purifying, concentrating, fractionating resin, and drying Fit Fiber # 80 (manufactured by Nippon Shokuhin Kako Co., Ltd.) with α-amylase and glucoamylase, used.
マルトデキストリンとしては、パインデックス#2(松谷化学工業株式会社製)を使用した。なお、マルトデキストリンは、難消化性グルカンと同等の着色となるように着色料(カラメル)を用いて色調を調整した。 As the maltodextrin, Paindex # 2 (manufactured by Matsutani Chemical Industry Co., Ltd.) was used. In addition, the color tone of maltodextrin was adjusted using a coloring agent (caramel) so that it might become the same color as indigestible glucan.
被験者の選択基準
被験者は、下記の選択基準に該当する者を対象とした。
1) 20歳以上、64歳以下の男女
2) スクリーニング検査の結果、事前検査で空腹時血糖値が110 mg/dL以上125 mg/dL以下に該当する者、または、事前検査で負荷食品摂取後30分の血糖値が140 mg/dL以上199 mg/dL以下に該当する者。
3) 食物繊維素材(難消化性デキストリン、ポリデキストロース、難消化性グルカンなど)を多く含む食品(特定保健用食品を含む)を常用していない者
4) 血糖代謝に影響を及ぼす可能性のある医薬品を服薬あるいは特定保健用食品や機能性表示食品を常用していない者
4) 試験の目的・内容について十分な説明を受け、同意能力があり、よく理解した上で自発的に参加を志願し、書面で試験参加に同意した者
Selection criteria for subjects The subjects were those who met the following selection criteria.
1) Males and
3) Those who do not regularly use foods (including foods for specified health use) that contain a lot of dietary fiber materials (indigestible dextrin, polydextrose, indigestible glucan, etc.) 4) May affect blood glucose metabolism Those who do not take medicines or use special health foods or functionally labeled foods 4) Receive sufficient explanation about the purpose and content of the study, have the ability to consent, and volunteer to participate voluntarily with understanding Those who have agreed to participate in the examination in writing
試験のデザイン
試験は、非投与群試験食品と投与群試験食品をそれぞれ単回摂取する無作為化二重盲検クロスオーバー試験を実施した。先ず被験者に対して事前検査3日前より食事記録を実施し、事前検査として、生活習慣アンケート、体調確認、計測、空腹時臨床検査(血液、尿)、食事負荷検査(水と共に摂取)を実施した。事前検査から4週間以上空け、摂取I期検査試験を実施した。摂取I期検査試験は、10時間以上の絶食後、早朝空腹時に負荷食品を摂取させた。負荷食品摂取後、経時的に採血した。摂取I期検査試験から1週間以上空け、摂取II期検査試験を実施した。被験者数は53名で行った。詳細な試験デザインは図4に示した。
Study design The study was a randomized, double-blind, crossover study with a single dose of each of the non-dose group test food and the dose group test food. First, meals were recorded for subjects from 3 days before the pre-examination, and as a pre-examination, lifestyle questionnaire, physical condition confirmation, measurement, fasting clinical examination (blood, urine), dietary load examination (taken with water) were conducted. . Ingestion phase I test was conducted for more than 4 weeks after the pre-inspection. Ingestion stage I testing test was to ingest the loaded food on an empty stomach early in the morning after fasting for 10 hours or more. After ingesting the loaded food, blood was collected over time. The intake phase II test was conducted after a period of one week or more from the intake phase I test. The number of subjects was 53. The detailed test design is shown in FIG.
なお、試験食品は、1包を約280mlの水に溶かしたものを、負荷食(市販の米飯300gと親子丼のもと210g)と同時に10分以内に残さず摂取した。 In addition, the test food which melt | dissolved 1 sachet in about 280 ml of water was ingested without remaining within 10 minutes simultaneously with a load meal (300 g of commercially available cooked rice and 210 g of oyakodon).
検査及び調査
試験に各項目を測定し、検査数値を比較して有効性を確認した。
1)主要評価項目:負荷食品摂取後の血糖値濃度時間曲線下面積(血糖AUC)
2)副次評価項目:空腹時血糖値、負荷食品摂取後30分、60分、90分、120分の血糖値、空腹時インスリン値、負荷食品摂取後30分、60分、90分、120分のインスリン値
Inspection and investigation Each item was measured in the test, and the effectiveness was confirmed by comparing the inspection values.
1) Primary endpoint: Area under the blood glucose concentration time curve after ingestion of loaded food (blood glucose AUC)
2) Secondary evaluation items: fasting blood glucose level, 30 minutes, 60 minutes, 90 minutes, 120 minutes after intake of loaded food, fasting insulin level, 30 minutes after intake of loaded food, 60 minutes, 90 minutes, 120 Insulin value in minutes
有効性に関する解析
血糖AUCについて、順序効果、時期効果を解析し、クロスオーバーデザインが適切であったことを確認した上で、各評価項目について一般線形モデルによる反復測定分散分析を用いて食品効果を評価した。
Analysis on effectiveness For blood glucose AUC, after analyzing the order effect and the timing effect, and confirming that the crossover design was appropriate, repeated analysis of variance using a general linear model was used for each evaluation item. The food effect was evaluated.
血糖値の経時的変化、インスリン値の経時的変化に関し、下記手順で比較した。
1) 投与群と非投与群における空腹時、負荷食品摂取後30分、60分、90分、120分について検査数値から、基本統計量(平均値、標準誤差)を算出する。
2) 負荷食摂取前、摂取後30、60、90、120分について投与群と非投与群の値を一般線形モデルによる反復測定分散分析を用いて食品効果を評価する。
The changes in blood glucose level over time and insulin level over time were compared by the following procedure.
1) Basic statistics (average value, standard error) are calculated from test values for fasting, 30 minutes, 60 minutes, 90 minutes, and 120 minutes after ingestion of loaded food in the administration group and the non-administration group.
2) Evaluate the food effect using repeated measures analysis of variance with a general linear model of the values of the administration group and the non-administration group for 30, 60, 90 and 120 minutes after ingestion of the loaded food.
血糖値のAUCに関し、下記手順で比較した。
1) 投与群と非投与群における空腹時、負荷食品摂取後30分、60分、90分、120分について検査数値から、基本統計量(平均値、標準誤差)を算出する。
2) 検査数値を基に、上記手順で算出した血糖値からTrapezoidal method(台形法)により血糖AUCを算出する。
3) 血糖AUCについて投与群と非投与群の値を一般線形モデルによる反復測定分散分析を用いて食品効果を評価する。
The AUC of blood glucose level was compared by the following procedure.
1) Basic statistics (average value, standard error) are calculated from test values for fasting, 30 minutes, 60 minutes, 90 minutes, and 120 minutes after ingestion of loaded food in the administration group and the non-administration group.
2) Based on the test value, the blood glucose AUC is calculated by the trapezoidal method (trapezoidal method) from the blood glucose level calculated in the above procedure.
3) For blood glucose AUC, evaluate the food effect using repeated measures analysis of variance with a general linear model for the values of the administration group and the non-administration group.
試験結果
血糖AUCを用いた時期効果(p=0.038)は認められたが、順序効果(p=0.393)は認められなかった。したがって、本研究の結果はクロスオーバーデザインに基づき適正に評価できると判断された。
Test results A time effect (p = 0.039) using blood glucose AUC was observed, but no order effect (p = 0.393) was observed. Therefore, it was judged that the results of this study can be properly evaluated based on the crossover design.
投与群と非投与群について血糖値の経時的変化、インスリン値の経時的変化について解析を行い、それぞれ図4および図5に示した。 The time-dependent change in blood glucose level and the time-dependent change in insulin level were analyzed for the administration group and the non-administration group, and are shown in FIGS. 4 and 5, respectively.
負荷食品摂取後60分の血糖値において分散分析の結果、投与群と非投与群の間に有意な差(p=0.043)が認められた。負荷食品摂取後90分の血糖値において分散分析の結果、投与群と非投与群の間に有意な差(p=0.044)が認められた。
As a result of analysis of variance at the
投与群と非投与群の血糖値のAUCついて解析を行い、図6に示した。 The AUC of the blood glucose level in the administration group and the non-administration group was analyzed and is shown in FIG.
血糖AUCにおいて分散分析の結果、投与群と非投与群の間に有意な差(p=0.042)が認められた。 As a result of analysis of variance in blood glucose AUC, a significant difference (p = 0.042) was observed between the administration group and the non-administration group.
本試験により、本発明における難消化性グルカンの摂取により、主要評価項目である血糖AUCでは非投与群と比べて有意な上昇抑制効果が認められ、副次評価項目である負荷食品摂取後60分、90分の血糖値においても、非投与群と比べて有意な上昇抑制効果が認められた。なお、その他の条件が有効性の判定に影響を与えていないことは被験者の記録から確認されている。また、本試験条件下では被験食品の安全性に問題はなかった。 In this test, the ingestion of indigestible glucan in the present invention showed a significant increase inhibitory effect in the blood glucose AUC as the main evaluation item compared with the non-administration group, and 60 minutes after the ingestion of the load food as the secondary evaluation item. Even at a blood glucose level of 90 minutes, a significant increase inhibitory effect was observed compared to the non-administered group. It is confirmed from the subject's records that other conditions do not affect the determination of effectiveness. There was no problem with the safety of the test food under the test conditions.
以上のことから、本発明による難消化性グルカンは血糖の上昇抑制作用を有しており、血糖上昇抑制剤として有用であることが示された。 From the above, it was shown that the indigestible glucan according to the present invention has a blood glucose increase inhibitory effect and is useful as a blood glucose increase inhibitor.
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Citations (3)
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JPH067093A (en) * | 1990-12-28 | 1994-01-18 | Sumitomo Metal Ind Ltd | Algin-containing food |
WO2008136331A1 (en) * | 2007-04-26 | 2008-11-13 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | BRANCHED α-GLUCAN, α-GLUCOSYLTRANSFERASE PRODUCING THE SAME, METHOD FOR PRODUCING THE SAME AND USE THEREOF |
JP2013076044A (en) * | 2011-01-07 | 2013-04-25 | Nippon Shokuhin Kako Co Ltd | Sugar condensate, method for producing same, and application therefor |
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JPH067093A (en) * | 1990-12-28 | 1994-01-18 | Sumitomo Metal Ind Ltd | Algin-containing food |
WO2008136331A1 (en) * | 2007-04-26 | 2008-11-13 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | BRANCHED α-GLUCAN, α-GLUCOSYLTRANSFERASE PRODUCING THE SAME, METHOD FOR PRODUCING THE SAME AND USE THEREOF |
JP2013076044A (en) * | 2011-01-07 | 2013-04-25 | Nippon Shokuhin Kako Co Ltd | Sugar condensate, method for producing same, and application therefor |
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