JP2008001668A - Agent for preventing or ameliorating lifestyle-related disease - Google Patents
Agent for preventing or ameliorating lifestyle-related disease Download PDFInfo
- Publication number
- JP2008001668A JP2008001668A JP2006175066A JP2006175066A JP2008001668A JP 2008001668 A JP2008001668 A JP 2008001668A JP 2006175066 A JP2006175066 A JP 2006175066A JP 2006175066 A JP2006175066 A JP 2006175066A JP 2008001668 A JP2008001668 A JP 2008001668A
- Authority
- JP
- Japan
- Prior art keywords
- cellooligosaccharide
- mass
- lifestyle
- concentration
- agent
- 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.)
- Granted
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Abstract
Description
本発明は、食品、医薬品分野の内用剤において、糖組成が制御され、血中アディポネクチン濃度の低下が抑制された、セロオリゴ糖を含有することで、肝臓内の中性脂肪、総コレステロール濃度を低下させる生活習慣病の予防または改善剤に関するものである。 The present invention contains a cellooligosaccharide having a controlled sugar composition and a suppressed decrease in blood adiponectin concentration in an internal preparation in the food and pharmaceutical fields, thereby reducing neutral fat and total cholesterol concentration in the liver. The present invention relates to an agent for preventing or improving lifestyle-related diseases.
セロオリゴ糖は、セロビオース、セロトリオース、セロテトラオース、セロペンタオース、セロヘキサオースの総称であり、1分子内に、グルコピラノース単位1〜6個が、β−1,4結合した少糖類である。
セロオリゴ糖は、ヒトには消化吸収され難く、低カロリー甘味料として有用であるのに加え、一般食品、機能性食品、化粧品、医薬品およびその添加剤、その他化学変換原料、発酵原料としても有用である(非特許文献1)。
Cellooligosaccharide is a generic name for cellobiose, cellotriose, cellotetraose, cellopentaose and cellohexaose, and is a oligosaccharide in which 1 to 6 glucopyranose units are β-1,4 linked in one molecule.
Cellooligosaccharides are difficult to digest and absorb by humans and are useful as low-calorie sweeteners, as well as general foods, functional foods, cosmetics, pharmaceuticals and their additives, other chemical conversion materials, and fermentation materials. Yes (Non-Patent Document 1).
本発明は、糖尿病、動脈硬化、肝硬変等の成人病態の要因となりうる肝臓内脂質に着目し、特定の糖組成を有し、血中アディポネクチン濃度の低下が抑制される、特定の糖組成を有するセロオリゴ糖を含有する生活習慣病予防または改善剤を服用することで、肝臓内脂質の低減効果を有するものである。 The present invention focuses on intrahepatic lipids that can cause adult pathological conditions such as diabetes, arteriosclerosis, and cirrhosis, and has a specific sugar composition that suppresses a decrease in blood adiponectin concentration. By taking a preventive or ameliorating agent for lifestyle-related diseases containing cellooligosaccharide, it has the effect of reducing lipids in the liver.
これまでのセロオリゴ糖による脂質代謝への試みについては、以下の報告がある。
非特許文献1〜3には、糖組成として、セロビオースが85.7質量%、セロトリオース質量3.7%、グルコース含量9.3質量%であるセロオリゴ糖を用い、高ショ糖食(ショ糖64.7質量部、カゼイン25質量部、コーン油5質量部、ミネラル4質量部、ビタミン1質量部、塩酸コリン0.2質量部およびビタミンE0.05質量部)の1または2.5質量%を、該セロオリゴ糖で置換し、SD系雄性ラットを4週間飼育した結果が記載されている。該文献によると、上記糖組成のセロオリゴ糖の摂取で、無添加系に対し、血清総コレステロール、HDL−コレステロール、トリグリセライド、体脂肪率が低下している。しかしながら、該文献のセロオリゴ糖は、血清脂質の低減効果を有するものの、肝臓等の内臓重量には変化がなく、内臓脂質ついても低減効果が認められていない。それに対し、本発明は、特定の糖組成を有し、血中アディポネクチン濃度の低下が抑制され、セロオリゴ糖を含有し、肝臓内の脂質低減効果に優れる生活習慣病の予防または改善剤である。従って、該文献の血清脂質低下性のセロオリゴ糖とは全く異なる。
The following reports have been made on attempts to lipid metabolism by cellooligosaccharides so far.
Non-Patent Documents 1 to 3 use a cellooligosaccharide having a cellobiose of 85.7% by mass, a cellotriose mass of 3.7%, and a glucose content of 9.3% by mass as a sugar composition. 7 parts by weight, 25 parts by weight casein, 5 parts by weight corn oil, 4 parts by weight mineral, 1 part by weight vitamin, 0.2 part by weight choline hydrochloride and 0.05 part by weight vitamin E) , The results of replacement with the cellooligosaccharide and breeding SD male rats for 4 weeks are described. According to this document, ingestion of cellooligosaccharide having the above-mentioned saccharide composition reduces serum total cholesterol, HDL-cholesterol, triglyceride, and body fat percentage relative to the additive-free system. However, although the cellooligosaccharides of this document have an effect of reducing serum lipids, there is no change in the visceral weight of the liver and the like, and no reduction effect has been observed for visceral lipids. On the other hand, the present invention is a preventive or ameliorating agent for lifestyle-related diseases that has a specific sugar composition, suppresses a decrease in blood adiponectin concentration, contains cellooligosaccharides, and is excellent in lipid reduction effect in the liver. Therefore, it is completely different from the serum lipid-lowering cellooligosaccharide of this document.
また、特許文献1には、乳酸菌(Lactbacillus rahamnosus)菌体とセロビオースを配合比で、1:2.5〜8含有せしめたことを特徴とする整腸及び脂質代謝促進用食・飼料添加物が記載されている。かかる文献では、基本食(カゼイン20.0部、DL−メオチニン0.3質量部、ミネラル3.5質量部、ビタミン1.0質量部、大豆油7.0質量部)の10質量%をセロビオースに置換し、Wister系雄性ラットを14日間飼育した結果が記載されている。該文献では、セロビオース単独添加系は、無添加に対し、血清、内臓の脂質代謝への効果はなく、セロビオースと上記乳酸菌を併用すると初めて、上記の脂質量が低減している。従って、本発明の如く、糖組成を高度に制御されたセロオリゴ糖を含有し、セロオリゴ糖単独で、肝臓内の脂肪量を低減する生活習慣病予防または改善剤とは本質的に異なる。また、該文献の脂質代謝促進食は、セロビオースと生菌を同時摂取する必要があるため、製剤とした場合の生菌の安定が悪く、服用するまでに、少なからず効果が低下する問題があった。
従って、特定の糖組成を有し、血中アディポネクチン濃度の低下が抑制された、インスリン非上昇性のセロオリゴ糖を有効成分とし、これを服用することで、肝臓内脂質を低減する生活習慣病予防または改善剤は知られていなかった。
Patent Document 1 discloses a food and feed additive for promoting intestinal regulation and lipid metabolism characterized by containing lactic acid bacteria (Lactobacillus rahamnosus) and cellobiose in a mixing ratio of 1: 2.5-8. Are listed. In this document, 10% by mass of the basic food (casein 20.0 parts, DL-meotiin 0.3 parts by mass, minerals 3.5 parts by mass, vitamins 1.0 parts by mass, soybean oil 7.0 parts by mass) is obtained. And the results of breeding Wister male rats for 14 days are described. In this document, the cellobiose-only addition system has no effect on serum and visceral lipid metabolism compared to the addition of cellobiose, and the amount of lipid is reduced only when cellobiose and the lactic acid bacterium are used in combination. Therefore, as in the present invention, it contains a cellooligosaccharide whose sugar composition is highly controlled, and the cellooligosaccharide alone is essentially different from a lifestyle-related disease prevention or amelioration agent that reduces the amount of fat in the liver. In addition, the lipid metabolism-promoting food of this document requires the simultaneous intake of cellobiose and viable bacteria, so that the stability of viable bacteria when prepared as a preparation is poor, and there is a problem that the effect is reduced to some extent by taking. It was.
Therefore, non-insulin-elevating cellooligosaccharides with a specific sugar composition and reduced blood adiponectin concentration are used as active ingredients, and by taking these, lifestyle-related disease prevention that reduces lipids in the liver Or the improving agent was not known.
本発明は、肝臓内の脂質低減性を有する生活習慣病予防または改善剤を提供することを目的とする。 An object of this invention is to provide the lifestyle-related disease prevention or improvement agent which has the lipid reduction property in a liver.
本発明者らは、糖組成を特定範囲に制御され、血中アディポネクチン濃度の低下が抑制された、セロオリゴ糖が、肝臓内の脂質低下性を有することを見出し、本発明をなすに至った。
すなわち、本発明は、下記の通りである。
(1)セロビオース含量が70質量%以上であり、セロトリオース、セロテトラオース、セロペンタオース、セロヘキサオースから選ばれる1種以上を0.1〜30質量%含み、グルコース含量が9質量%以下であるセロオリゴ糖を有効成分として含有することを特徴とする生活習慣病予防または改善剤。
(2)上記オリゴ糖が、肝臓内の中性脂肪濃度の低下率が15%以上のオリゴ糖であることを特徴とする上記(1)の生活習慣病予防または改善剤。
(3)上記オリゴ糖が、経口摂取による血中アディポネクチン濃度の低下率が30%以下のオリゴ糖であることを特徴とする上記(1)の生活習慣病予防または改善剤。
(4)上記(1)〜(3)の生活習慣病予防または改善剤を含有する医薬品。
(5)上記(1)〜(3)の生活習慣病予防または改善剤を含有する食品。
The present inventors have found that cellooligosaccharides whose sugar composition is controlled within a specific range and in which the decrease in blood adiponectin concentration is suppressed have lipid lowering properties in the liver, have led to the present invention.
That is, the present invention is as follows.
(1) Cellobiose content is 70% by mass or more, 0.1 to 30% by mass of one or more selected from cellotriose, cellotetraose, cellopentaose and cellohexaose, and glucose content of 9% by mass or less A preventive or ameliorating agent for lifestyle-related diseases characterized by containing a certain cellooligosaccharide as an active ingredient.
(2) The preventive or ameliorating agent for lifestyle-related diseases according to (1), wherein the oligosaccharide is an oligosaccharide having a reduction rate of neutral fat concentration in the liver of 15% or more.
(3) The preventive or ameliorating agent for lifestyle-related diseases according to (1), wherein the oligosaccharide is an oligosaccharide having a reduction rate of blood adiponectin concentration by oral intake of 30% or less.
(4) A pharmaceutical comprising the lifestyle-related disease prevention or ameliorating agent according to (1) to (3) above.
(5) A food containing the lifestyle-related disease prevention or ameliorating agent according to (1) to (3) above.
本発明の生活習慣病予防または改善剤を服用することで、肝臓内の脂質を低減できる。 By taking the lifestyle-related disease prevention or ameliorating agent of the present invention, lipids in the liver can be reduced.
本発明について、特にその好ましい態様を中心に、以下具体的に説明する。
本発明におけるセロオリゴ糖は、セロビオースを70質量%以上含有する必要がある。セロビオース含量が高いほど、セロオリゴ糖の水溶解度が向上し、服用時の生体利用率が高まるため好ましい。このセロビオース含量は、86質量%以上が好ましく、90質量%以上がより好ましく、95質量%以上が特に好ましい。
The present invention will be specifically described below, particularly focusing on preferred embodiments thereof.
The cellooligosaccharide in this invention needs to contain 70 mass% or more of cellobiose. A higher cellobiose content is preferable because the water solubility of the cellooligosaccharide is improved and the bioavailability at the time of taking is increased. The cellobiose content is preferably 86% by mass or more, more preferably 90% by mass or more, and particularly preferably 95% by mass or more.
本発明におけるセロオリゴ糖におけるセロトリオース、セロテトラオース、セロペンタオース、セロヘキサオースから選ばれる1種以上の含量は、0.1〜30質量%である。これらを含有することで、肝臓脂質の低下効果が高められる。但し、含量が高すぎると、溶解度が低くなり、上述の生体利用率が低減する。従って、この含量は上述の範囲を満たす必要がある。好ましい範囲は、0.1〜14質量%であり、0.1〜5質量%がより好ましい。
本発明におけるセロオリゴ糖のグルコース含量は、9質量%以下である。グルコース含量が低いことで、血中インスリン濃度の上昇を抑え、特に肝臓内の脂質代謝を高めることができる。グルコース含量は、3.5質量%以下が好ましく、2質量%以下がより好ましい。グルコース含量は、低いほど、上述の効果が大きくなるため、その下限値は特に制限されるものではない。
In the cellooligosaccharide according to the present invention, the content of one or more selected from cellotriose, cellotetraose, cellopentaose and cellohexaose is 0.1 to 30% by mass. By containing these, the effect of reducing liver lipids is enhanced. However, if the content is too high, the solubility is lowered and the above-mentioned bioavailability is reduced. Therefore, this content needs to satisfy the above-mentioned range. A preferable range is 0.1 to 14% by mass, and more preferably 0.1 to 5% by mass.
The glucose content of the cellooligosaccharide in the present invention is 9% by mass or less. A low glucose content can suppress an increase in blood insulin concentration, and particularly increase lipid metabolism in the liver. The glucose content is preferably 3.5% by mass or less, and more preferably 2% by mass or less. The lower the glucose content, the greater the above-mentioned effect, so the lower limit is not particularly limited.
以下に、本発明の生活習慣病予防または改善剤におけるセロオリゴ糖、グルコース含量の分析法を記す。本発明のセロオリゴ糖は、純水に1質量%濃度で溶解させた後、高速液体クロマトグラフィー(クロマトグラフィーシステム:島津製作所(株)製 商品名 SCL−10A、カラム:島津製作所製 商品名 Asahipak NH2P−50、移動相:アセトニトリルまたは水=75/25(容積比))で分析できる。セロオリゴ糖の糖組成は、上述の方法で得られたクロマトグラムにおけるセロビオース、セロトリオース、セロテトラオース、セロペンタオース、セロヘキサオースのピーク面積を質量換算し、総質量に占める、それぞれの質量百分率で表される。グルコースの含有率も、同様の方法で求められ、セロビオースとグルコースのピーク面積から算出される総質量に対するグルコースの質量の百分率で表される。 Below, the analysis method of the cellooligosaccharide and glucose content in the lifestyle-related disease prevention or improvement agent of this invention is described. The cellooligosaccharide of the present invention is dissolved in pure water at a concentration of 1% by mass and then subjected to high performance liquid chromatography (chromatography system: manufactured by Shimadzu Corporation, trade name: SCL-10A, column: manufactured by Shimadzu Corporation, trade name: Asahipak NH 2 P-50, mobile phase: acetonitrile or water = 75/25 (volume ratio)). The sugar composition of cellooligosaccharides is the mass percentage of the cell biose, cellotriose, cellotetraose, cellopentaose, cellohexaose peak area in the chromatogram obtained by the above method, and occupies the total mass. expressed. The content rate of glucose is also obtained by the same method, and is expressed as a percentage of the mass of glucose with respect to the total mass calculated from the peak areas of cellobiose and glucose.
本発明のセロオリゴ糖は、インスリン非上昇性であることが好ましい。このインスリン非上昇性とは、セロオリゴ糖を経口摂取した後の血中インスリン濃度が、経口摂取前のインスリン濃度に対し、上昇しないことを意味し、以下の方法で測定される。生後7週齢のSDラットを1週間AIN−93G(オリエンタル酵母工業製)の自由摂取で、1週間予備飼育後、16時間絶食させ、表1の各セロオリゴ糖水溶液を、ゾンデを用いて1500mg/kgを投与した。投与前および投与後、30分後に無麻酔下で、骸外静脈より採血し、インスリン濃度(ng/mL シバヤギ製 レビインスリンキット使用)を測定した。ここでいうインスリン非上昇性とは、上記のインスリン濃度の上昇率が、30%以下となることである。より好ましくは、インスリン濃度の上昇率が25%以下であり、特に好ましくは、20%以下である。 The cellooligosaccharide of the present invention is preferably non-insulin-elevating. This non-insulin-elevating property means that the blood insulin concentration after oral intake of cellooligosaccharide does not increase with respect to the insulin concentration before oral intake, and is measured by the following method. Seven-week-old SD rats were allowed free intake of AIN-93G (manufactured by Oriental Yeast Co., Ltd.) for 1 week, fasted for 1 week, fasted for 16 hours, and each cellooligosaccharide aqueous solution in Table 1 was 1500 mg / day using a sonde. kg was administered. Blood samples were collected from the extracorporeal vein under anesthesia before and 30 minutes after the administration, and the insulin concentration (ng / mL Shibayagi Levi insulin kit was used) was measured. The term “insulin non-rising property” as used herein means that the rate of increase in the insulin concentration is 30% or less. More preferably, the rate of increase in insulin concentration is 25% or less, and particularly preferably 20% or less.
本発明のセロオリゴ糖は、経口摂取時の血中アディポネクチン濃度の低下率が30%以下であることが好ましい。血中アディポネクチン濃度は、脂質代謝異常の指標であり、この低下率が小さいと、糖尿病、動脈硬化等の生活習慣病を生じないため好ましい。ここでいう、血中アディポネクチン濃度とは、血液を用いてELISA法(大塚製薬製 血中アディポネクチンELISAキット)で測定したアディポネクチン濃度(μg/mL−血液)のことである。その低下率とは、セロオリゴ糖の摂取と非摂取の血液を用い測定したアディポネクチン濃度から、以下の式で求められる。低下率(%)=((セロオリゴ糖非摂取時の濃度)−(セロオリゴ糖摂取時の濃度))/(セロオリゴ糖非摂取時の濃度)(%)。アディポネクチン低下率は小さいほど、上述の効果が大きくなるため、25%以下がより好ましい。 The cellooligosaccharide of the present invention preferably has a reduction rate of blood adiponectin concentration of 30% or less when taken orally. The blood adiponectin concentration is an index of abnormal lipid metabolism, and a low decrease rate is preferable because lifestyle-related diseases such as diabetes and arteriosclerosis do not occur. The blood adiponectin concentration referred to here is the adiponectin concentration (μg / mL-blood) measured by ELISA using blood (adiponectin ELISA kit manufactured by Otsuka Pharmaceutical Co., Ltd.). The rate of decrease can be determined by the following formula from the concentration of adiponectin measured using ingested and non-ingested cellooligosaccharides. Decrease rate (%) = ((concentration when cellooligosaccharide is not taken) − (concentration when cellooligosaccharide is taken)) / (concentration when cellooligosaccharide is not taken) (%). The smaller the adiponectin reduction rate, the greater the above-mentioned effect, so 25% or less is more preferable.
本発明のセロオリゴ糖は、肝臓内の中性脂肪濃度の低下率が15%以上であることが好ましい。この肝臓内の中性脂肪濃度の低下率が高いほど、糖尿病、動脈硬化、肝不全、肝硬変等の生活習慣病の予防/改善効果が高い。ここでいう、中性脂肪濃度とは、肝臓の単位量当たりに存在する中性脂肪量(mg/g−Wetliver)のことである。その低下率とは、セロオリゴ糖の摂取と非摂取の肝臓内の中性脂肪濃度から、以下の式で求められる。低下率(%)=((セロオリゴ糖非摂取時の濃度)−(セロオリゴ糖摂取時の濃度))/(セロオリゴ糖非摂取時の濃度)(%)。中性脂肪濃度の低下率は大きいほど、上述の効果が大きくなる。従って、20%以上であることがより好ましい。 The cellooligosaccharide of the present invention preferably has a reduction rate of neutral fat concentration in the liver of 15% or more. The higher the reduction rate of the neutral fat concentration in the liver, the higher the effect of preventing / ameliorating lifestyle-related diseases such as diabetes, arteriosclerosis, liver failure, and cirrhosis. The neutral fat concentration referred to here is the amount of neutral fat (mg / g-Wetliver) present per unit amount of the liver. The rate of decrease can be determined by the following formula from the intake of cellooligosaccharide and the neutral fat concentration in the non-ingested liver. Decrease rate (%) = ((concentration when cellooligosaccharide is not taken) − (concentration when cellooligosaccharide is taken)) / (concentration when cellooligosaccharide is not taken) (%). The above-mentioned effect becomes large, so that the fall rate of neutral fat concentration is large. Therefore, it is more preferably 20% or more.
本発明のセロオリゴ糖は、肝臓内の総コレステロール濃度の低下率が10%以上であることが好ましい。この肝臓内の総コレステロールの低下率が高いほど、糖尿病、動脈硬化、肝不全、肝硬変等の生活習慣病の予防/改善効果が高い。ここでいう、総コレステロール濃度も、上述の中性脂肪濃度と同様に、肝臓の単位量当たりに存在する総コレステロール量(mg/g−Wetliver)のことである。その低下率とは、セロオリゴ糖の摂取と非摂取の肝臓内の総コレステロール濃度から、以下の式で求められる。低下率(%)=((セロオリゴ糖非摂取時の濃度)−(セロオリゴ糖摂取時の濃度))/(セロオリゴ糖非摂取時の濃度)(%)。総コレステロール濃度の低下率は大きいほど、上述の効果が大きくなる。従って、15%以上であることがより好ましい。 The cellooligosaccharide of the present invention preferably has a reduction rate of the total cholesterol concentration in the liver of 10% or more. The higher the reduction rate of total cholesterol in the liver, the higher the prevention / improvement effect of lifestyle-related diseases such as diabetes, arteriosclerosis, liver failure, and cirrhosis. The total cholesterol concentration here is also the total cholesterol amount (mg / g-Wetliver) present per unit amount of the liver, like the neutral fat concentration described above. The rate of decrease is determined by the following formula from the intake of cellooligosaccharide and the total cholesterol concentration in the non-intake liver. Decrease rate (%) = ((concentration when cellooligosaccharide is not taken) − (concentration when cellooligosaccharide is taken)) / (concentration when cellooligosaccharide is not taken) (%). The above-mentioned effect becomes large, so that the fall rate of total cholesterol concentration is large. Therefore, it is more preferably 15% or more.
本発明の生活習慣病予防とは、本発明のセロオリゴ糖を有効成分とする予防剤を経口摂取することで、高糖質、高脂質、高カロリー等の食事を摂取した場合も、血中および内臓脂質の上昇を抑制し、糖尿病、動脈硬化、肥満、肝不全、肝硬変等の生活習慣病を予防できることである。
一方、本発明の生活習慣病改善とは、上述の生活習慣病を発病した状態から、本発明のセロオリゴ糖を摂取することで、血中および内臓脂質を低減し、上述の生活習慣病を改善することである。本発明のセロオリゴ糖を有効成分とする生活習慣病予防/改善剤を経口摂取すると、上述の予防と改善の効果が得られる。
The prevention of lifestyle-related diseases of the present invention means that the preventive agent comprising the cellooligosaccharide of the present invention as an active ingredient is taken orally, even when a high sugar, high fat, high calorie or other meal is ingested in the blood and It is possible to suppress the increase in visceral lipids and prevent lifestyle-related diseases such as diabetes, arteriosclerosis, obesity, liver failure, and cirrhosis.
On the other hand, the lifestyle-related disease improvement of the present invention is to reduce the blood and visceral lipids and improve the above-mentioned lifestyle-related diseases by ingesting the cellooligosaccharide of the present invention from the state in which the above-mentioned lifestyle-related diseases have occurred. It is to be. If the lifestyle-related disease prevention / amelioration agent comprising the cellooligosaccharide of the present invention as an active ingredient is taken orally, the above-mentioned prevention and improvement effects can be obtained.
本発明の生活習慣病予防/改善剤は、肝臓内の中性脂肪濃度および総コレステロール濃度の低下作用を有するものであるが、経口摂取により、血中脂質、肝臓以外の内臓脂質についても低下効果を有するものである。
本発明でいう血中脂質とは、血中の中性脂肪、HDL、LDL−コレステロール、リン脂質のことであり、血清または血漿を用い公知の測定方法で求められるものである。血中脂質の低下とは、上記の血中脂質の濃度を測定し、セロオリゴ糖の投与前の値、もしくはセロオリゴ糖非投与状態から低下していることである。
The lifestyle-related disease preventive / ameliorating agent of the present invention has an action of lowering the neutral fat concentration and total cholesterol concentration in the liver. However, when taken orally, it also lowers blood lipids and visceral lipids other than the liver. It is what has.
The blood lipid as used in the present invention means blood neutral fat, HDL, LDL-cholesterol, and phospholipid, and is determined by a known measurement method using serum or plasma. The decrease in blood lipid means that the concentration of the above-mentioned blood lipid is measured, and is decreased from the value before administration of cellooligosaccharide or from the cellooligosaccharide non-administration state.
また、本発明の内臓脂質とは、上述の肝臓内の中性脂肪、総コレステロール濃度に加え、肝臓内のHDL、LDL−コレステロール、リン脂質濃度、精巣上体の副睾丸脂質、腎臓周囲の腹腔内に存在する上述の脂質のことである。これらついても、血中脂質と同様に脂質濃度、または質量で表され、内臓脂質濃度の低下とは、セロオリゴ糖の投与前、もしくはセロオリゴ糖非投与状態から脂質濃度、または質量が低下していることを意味する。 Further, the visceral lipids of the present invention include the above-mentioned neutral fat and total cholesterol concentration in the liver, HDL, LDL-cholesterol, phospholipid concentration, epididymal lipids in the epididymis, and the peritoneal cavity around the kidney. It is the above-mentioned lipid existing in the inside. These are also expressed in lipid concentration or mass in the same way as blood lipids. The decrease in visceral lipid concentration means that the lipid concentration or mass has decreased before or after administration of cellooligosaccharide. Means that.
次に、本発明のセロオリゴ糖の製造方法について説明する。
本発明のセロオリゴ糖の起源には、特に制限はなく、セルロース系物質の加水分解で製造されたもの、グルコース等の単糖類またはその誘導体を縮合または糖転移させ製造されたものでもよいが、酵素分解法で得られたものが、安全性の点で好ましい。
酵素分解に使用するセルロース系物質としては、植物性でも、動物性でもよく、例えば、木材、竹、コットン、ラミー、ホヤ、バガス、ケナフ、麦、稲、バクテリアセルロース等の含有する天然物由来の繊維質物質、またそれらを一旦溶剤に溶解させ再生させた再生セルロースでも、それらの化学処理を施しセルロース誘導体としたものでもよく、上記のうち、1種または2種以上を併用してもよい。これらの中でも、溶解または化学処理を経ない、天然セルロース系物質を用いると、得られたセロオリゴ糖に人体に有害な溶剤または化学物質が含まれないため好ましい。また、セルロース系物質は精製パルプの状態で使用することが好ましく、パルプの精製方法には特に制限はなく、サルファイトパルプ、クラフトパルプ、NBKPパルプ等のいずれのパルプを使用してもよい。
Next, the manufacturing method of the cellooligosaccharide of this invention is demonstrated.
The origin of the cellooligosaccharide of the present invention is not particularly limited, and may be one produced by hydrolysis of a cellulosic material, one produced by condensation or sugar transfer of a monosaccharide such as glucose or a derivative thereof, What was obtained by the decomposition method is preferable in terms of safety.
Cellulosic substances used for enzymatic degradation may be plant or animal, and may be derived from natural products such as wood, bamboo, cotton, ramie, squirts, bagasse, kenaf, wheat, rice, and bacterial cellulose. Fibrous substances, or regenerated cellulose that has been regenerated by dissolving them in a solvent, may be those obtained by subjecting them to chemical treatment to give cellulose derivatives, and one or more of the above may be used in combination. Among these, natural cellulosic substances that do not undergo dissolution or chemical treatment are preferable because the obtained cellooligosaccharides do not contain solvents or chemical substances harmful to the human body. Moreover, it is preferable to use a cellulosic substance in the state of a refined pulp, and there is no restriction | limiting in particular in the refinement | purification method of a pulp, You may use any pulp, such as a sulfite pulp, a kraft pulp, and NBKP pulp.
また、セルロース系物質を酵素分解する場合には、使用するセルロース系物質としては、一旦加水分解し、平均重合度を700以下に部分加水分解したセルロース系物質を用いると、セロオリゴ糖の収率を向上させる上で好ましい。さらに、該特定の重合度を有するセルロース系物質は、平均粒子径を100μm以下、コロイド状セルロース成分含有量を10質量%以上に制御したものを用いることが、酵素分解速度の向上、セロオリゴ糖選択率が向上するため好ましい。 In the case of enzymatically decomposing a cellulosic material, the cellulosic material used is a cellulosic material that is once hydrolyzed and partially hydrolyzed to an average polymerization degree of 700 or less. It is preferable in terms of improvement. Furthermore, it is possible to use a cellulosic material having a specific degree of polymerization with an average particle size of 100 μm or less and a colloidal cellulose component content of 10% by mass or more to improve the enzymatic degradation rate and select cellooligosaccharides. This is preferable because the rate is improved.
本発明では、セルロース系物質の加水分解に用いる酵素をセルラーゼといい、本発明で使用するセルラーゼとは、セルロースを分解する酵素の総称であり、セルロースへの分解活性を有していれば、本発明でいうセルラーゼに含まれる。セルラーゼ酵素源としては、例えば、セルラーゼ産生生菌体そのもの、セルラーゼ産生菌が分泌する酵素を精製したもの、精製酵素を賦形剤、安定化剤等の添加剤ともに製剤化したもの等が挙げられる。セルラーゼ製剤品の場合、それに添加される添加剤にも特に制限はなく、その剤形は、粉末、顆粒、液体等いずれでもよい。 In the present invention, an enzyme used for hydrolysis of a cellulosic substance is referred to as cellulase, and the cellulase used in the present invention is a general term for enzymes that decompose cellulose. It is included in the cellulase referred to in the invention. Cellulase enzyme sources include, for example, cellulase-producing living cells themselves, purified enzyme secreted by cellulase-producing bacteria, and formulated purified enzyme together with excipients, stabilizers and other additives. . In the case of a cellulase preparation, the additive added thereto is not particularly limited, and the dosage form may be any of powder, granule, liquid and the like.
セルラーゼの起源についても、特に制限はないが、例えば、公知のセルラーゼを生産する微生物としては、トリコデルマ(Tricoderma)属、アクレモニウム(Acremonium)属、アスペルギルス(Aspergillus)属、バチルス(Bacillus)属、シュードモナス(Pseudomonas)属、ペニシリウム(Penicillium)属、アエロモナス(Aeromonus)属、イルペックス(Irpex)属、スポロトリクム(Sporotrichum)属、フミコーラ(Humicola)属、セロビブリオ(Cellovibrio)属等の「セルラーゼ」(講談社サイエンティフィック発行(1987))、「セルロースの事典」(朝倉書店発行(2000))に記載される菌が生産するセルラーゼを挙げることができるが、セルロースを分解する酵素であれば、上記公知の菌由来の酵素に限らず、新規の菌由来の酵素も、本発明のセルラーゼに含まれる。
酵素分解方法は、公知の方法を使用すればよく、特に制限されるものではないが、一例としては、セルロース系物質を水性媒体中に懸濁させ、セルラーゼを添加し、攪拌または振とうしながら、加温して糖化反応を行う方法が挙げられる。
The origin of cellulase is not particularly limited. For example, microorganisms that produce known cellulases include the genus Tricodederma, the genus Acremonium, the genus Aspergillus, the genus Bacillus, and the pseudomonas. (Pseudomonas genus), Penicillium genus, Aeromonus genus, Irpex genus, Sporotrichum genus, Humicola genus, Cellobibrio celioc Issued (1987)), and the fungus described in "Encyclopedia of Cellulose" (published by Asakura Shoten (2000)) is produced. It can be exemplified cellulase, if enzymes that degrade cellulose, not only the enzyme derived from the known bacteria, enzymes from novel microorganisms are also included in cellulase of the present invention.
The enzymatic decomposition method may be any known method, and is not particularly limited. For example, the cellulosic material is suspended in an aqueous medium, cellulase is added, and stirring or shaking is performed. And a method of performing a saccharification reaction by heating.
上記方法において、懸濁方法、攪拌方法、セルラーゼ・基質の添加方法・添加順序、それらの濃度等の反応条件は、セロオリゴ糖がより高収率で得られるよう適宜調整されるものである。その際の、反応液のpH及び温度は、酵素が失活しない範囲内であればよく、一般的には、常圧で反応を行う場合、温度は5〜95℃、pHは1〜11の範囲でよい。また、この圧力、温度、pHについても、上記同様、セロオリゴ糖がより高収率で得られるよう適宜調整されるものである。 In the above method, the suspension method, the stirring method, the addition method / order of addition of cellulase / substrate, the concentration thereof, and other reaction conditions are appropriately adjusted so that the cellooligosaccharide can be obtained in a higher yield. In this case, the pH and temperature of the reaction solution may be within the range in which the enzyme is not inactivated. Range may be sufficient. Further, the pressure, temperature, and pH are appropriately adjusted so that the cellooligosaccharide can be obtained in a higher yield, as described above.
上述の酵素分解により得られたセロオリゴ糖水溶液は、必要に応じて、脱色、脱塩、酵素除去等の精製処理を施すことができる。精製方法は、公知の方法であれば特に制限されないが、例えば、活性炭処理、イオン交換樹脂処理、クロマトグラフィー処理、精密ろ過、限外ろ過、逆浸透ろ過等の濾過処理、晶析処理等を使用してもよく、これらを単独で使用しても、2種以上を組み合わせてもよい。
セロオリゴ糖の精製方法の中でも、晶析処理は、セロオリゴ糖の組成を制御しやすいため好ましい。
The cellooligosaccharide aqueous solution obtained by the above enzymatic decomposition can be subjected to purification treatment such as decolorization, desalting, enzyme removal, etc., if necessary. The purification method is not particularly limited as long as it is a known method. For example, activated carbon treatment, ion exchange resin treatment, chromatography treatment, microfiltration, ultrafiltration, reverse osmosis filtration and other filtration treatments, crystallization treatment, etc. are used. These may be used alone or in combination of two or more.
Among the cellooligosaccharide purification methods, the crystallization treatment is preferable because the composition of the cellooligosaccharide is easy to control.
酵素分解法の一例としては、例えば、特願2004−218902、特願2004−323579、特願2005−125966、特願2005−125975、特願2006−041149(いずれも出願人:旭化成ケミカルズ株式会社)に開示される方法で製造されたセロオリゴ糖を使用することが好ましい。 As an example of the enzymatic decomposition method, for example, Japanese Patent Application No. 2004-218902, Japanese Patent Application No. 2004-323579, Japanese Patent Application No. 2005-125966, Japanese Patent Application No. 2005-125975, and Japanese Patent Application No. 2006-041149 (all applicants: Asahi Kasei Chemicals Corporation). It is preferable to use cellooligosaccharides produced by the method disclosed in.
次に本発明のセロオリゴ糖を有効成分とする生活習慣病予防/改善剤について説明する。
本発明のセロオリゴ糖を有効成分とする生活習慣病予防/改善剤は、本発明のセロオリゴ糖を粉末状で、単独で使用しても、水溶液または分散液として使用しても、本発明のセロオリゴ糖に加え、食品素材、化粧品素材、医薬品薬効成分、またはそれらで使用される添加物の中から選択される1種以上の構成成分に含有され、顆粒、成型体、水溶液、水分散体、ペースト、ゲル状の食品/医薬品として使用してもよい。
Next, the lifestyle-related disease prevention / amelioration agent which uses the cellooligosaccharide of this invention as an active ingredient is demonstrated.
The preventive / ameliorating agent for lifestyle-related diseases comprising the cellooligosaccharide of the present invention as an active ingredient, whether the cellooligosaccharide of the present invention is used in powder form, alone or as an aqueous solution or dispersion, In addition to sugar, it is contained in one or more components selected from food materials, cosmetic materials, medicinal medicinal ingredients, or additives used in them, granules, molded products, aqueous solutions, aqueous dispersions, pastes It may be used as a gel food / medicine.
本発明の生活習慣病予防または改善剤におけるセロオリゴ糖の配合量は、0.01〜100質量%が好ましい。ここでいうセロオリゴ糖の配合量とは、本発明の生活習慣病予防/改善剤に含有されるセロビオース、セロトリオース、セロテトラオース、セロペンタオース、セロヘキサオースの総量であり、このセロオリゴ糖の配合量が、0.01質量%未満では、血中及び又は内臓の脂質代謝において充分な効果が得られないため好ましくない。セロオリゴ糖配合量は高いほど、上述の脂質代謝効果が促進されるため、より好ましい範囲としては0.6質量%以上であり、特に好ましくは、0.75質量%以上である。
本発明の生活習慣病予防/改善剤は、本発明のセロオリゴ糖に加え、グルコース以外の少糖類または高甘味度甘味料を含んでもよい。セロオリゴ糖と少糖類、または高甘味度甘味料の配合比は、本発明の効果が得られれば制限されるものではないが、例えばセロオリゴ糖または少糖類の質量比で、0.1/99.9〜99.9/0.1である。
特に、難消化性の少糖類を添加することで、セロオリゴ糖の脂質代謝に加え、腸内有用細菌の賦活等の整腸作用も得られるため好ましい。さらに、本発明のセロオリゴ糖に、高甘味度甘味料を添加すると、セロオリゴ糖のカロリーを増加させずに、味質を調整できるため好ましい。
As for the compounding quantity of the cellooligosaccharide in the lifestyle-related disease prevention or improvement agent of this invention, 0.01-100 mass% is preferable. The amount of cellooligosaccharide here is the total amount of cellobiose, cellotriose, cellotetraose, cellopentaose and cellohexaose contained in the lifestyle-related disease prevention / amelioration agent of the present invention. If the amount is less than 0.01% by mass, a sufficient effect cannot be obtained in lipid metabolism in blood and / or viscera, which is not preferable. The higher the amount of cellooligosaccharide is, the more the above-described lipid metabolism effect is promoted. Therefore, the more preferable range is 0.6% by mass or more, and particularly preferably 0.75% by mass or more.
The lifestyle-related disease preventing / ameliorating agent of the present invention may contain a oligosaccharide other than glucose or a high-intensity sweetener in addition to the cellooligosaccharide of the present invention. The mixing ratio of the cellooligosaccharide and oligosaccharide or the high-intensity sweetener is not limited as long as the effects of the present invention are obtained. For example, the mass ratio of cellooligosaccharide or oligosaccharide is 0.1 / 99. 9-99.9 / 0.1.
In particular, the addition of indigestible oligosaccharides is preferable because in addition to lipid metabolism of cellooligosaccharides, intestinal regulation such as activation of useful intestinal bacteria can be obtained. Furthermore, it is preferable to add a high-intensity sweetener to the cellooligosaccharide of the present invention because the taste can be adjusted without increasing the calorie of the cellooligosaccharide.
この少糖類としては、例えば、ガラクトース、フラクトース、マンノース、アラビノース、ラムノース、リボース、キシロース、ソルボース等の単糖類およびそれらの還元物、スクロース、メリビオース、トレハロース、ラクトース、マルトース、ゲンチオビオース、ラミナリビオース、ラクチュロース、キシロビオース等の2糖類およびそれらの還元物、ラクトスクロース、ラフィノース、マルトトトリオース、イソマルトース、パラチノース、ケストース、ゲンチオシルセロビオース等の3糖類およびそれらの還元物、マルトテトラオース、ゲンチオシルセロトリオース、ニストース等の4糖類およびそれらの還元物、マルトペンタオース、マルトヘキサオース等の5または6糖類およびそれらの還元物、β−シクロデキストリン、γ−シクロデキストリン、デキストラン等の環状少糖類、難消化性デキストリン、ポリデキストロース、アラビアガム、カルボキシメチルセルロース、グアーガム、カードラン等の水溶性多糖類およびそれらの還元物、ソルビトール、キシリトール、マルチロール、マンニトール、ラクチトール等の糖アルコール等の「食品添加物公定書」(廣川書店発行)に甘味料として分類されるものが含まれる。これらの少糖類は、少糖類そのままであっても、溶解性等を改善する目的で、その化学構造の一部を、カルボキシル化、エチル化、メチル化、硫酸エステル化等の化学処理を施し、誘導体としたものを使用してもよい。 Examples of the oligosaccharide include saccharides such as galactose, fructose, mannose, arabinose, rhamnose, ribose, xylose, sorbose and their reduced products, sucrose, melibiose, trehalose, lactose, maltose, gentiobiose, laminaribiose, lactulose. Disaccharides such as xylobiose and their reduced products, lactosucrose, raffinose, maltototriose, isomaltose, palatinose, kestose, trisaccharides such as gentiosil cellobiose and their reduced products, maltotetraose, gentiosyl cellotri Tetrasaccharides such as ose and nystose and their reduced products, 5 or 6 saccharides such as maltopentaose and maltohexaose and their reduced products, β-cyclodextrin, γ-si Cyclodextrins, cyclic oligosaccharides such as dextran, indigestible dextrin, polydextrose, gum arabic, carboxymethylcellulose, guar gum, curdlan and other water-soluble polysaccharides and their reduced products, sorbitol, xylitol, multirole, mannitol, lactitol Such as sugar alcohols, etc. are classified as sweeteners in the “Food Additives Official Document” (published by Yodogawa Shoten). These oligosaccharides are subjected to chemical treatments such as carboxylation, ethylation, methylation, sulfate esterification, etc., for the purpose of improving solubility and the like even if the oligosaccharides are intact. A derivative may be used.
高甘味度甘味料としては、サッカリン、甘草(グリチルリチン)、ステビア、アスパルテーム、スクラロース、アセスルファムカリウム等の「食品添加物公定書」(廣川書店発行)に高甘味度甘味料として分類されるものが含まれる。これらの高甘味度甘味料も、甘味料そのままであっても、その化学構造の一部を他の置換機に置き換え、誘導体としたものを使用してもよい。 High-intensity sweeteners include those classified as high-intensity sweeteners in the “Food Additive Official Document” (published by Yodogawa Shoten) such as saccharin, licorice (glycyrrhizin), stevia, aspartame, sucralose, and acesulfame potassium. It is. These high-intensity sweeteners may be used as they are, or derivatives obtained by substituting a part of the chemical structure with other substitution machines.
本発明でいう構成成分とは、セロオリゴ糖以外の少糖類、高甘味度甘味料、食品素材、化粧品素材、医薬品薬効成分、色素、香料、金属、セラミックス又は賦形剤、崩壊剤、結合剤、流動化剤、滑沢剤、矯味剤、着色剤、甘味剤、溶剤、油脂、界面活性剤、増粘剤、ゲル化剤等の添加剤のことであり、粉体状、結晶状、油状、液状、半固形状などいずれの形態でもよく、例えば「食品添加物公定書」(廣川書店発行)、「化粧品原料基準」、「化粧品種別配合成分規格」(いずれも薬事日報社発行)、「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社発行)に記載のものを用いることが可能である。
また、それらは種々の目的でコーティング、リポソーム化等の加工を施したものであってもよい。これらの構成成分は単独で使用しても、複数を併用してもよい。本発明の生活習慣病予防または改善剤は、溶解、混合、分散、造粒、溶融・固化、圧縮、乾燥等の公知の方法で加工できる。
Constituents referred to in the present invention include oligosaccharides other than cellooligosaccharides, high-intensity sweeteners, food materials, cosmetic materials, pharmaceutical medicinal ingredients, pigments, fragrances, metals, ceramics or excipients, disintegrants, binders, It is an additive such as fluidizer, lubricant, flavoring agent, colorant, sweetener, solvent, fats and oils, surfactant, thickener, gelling agent, powder, crystal, oil, It can be in any form, such as liquid or semi-solid, for example, “Food Additives Official Document” (published by Yodogawa Shoten), “Cosmetic Raw Material Standards”, “Composition Standards by Cosmetic Variety” (both published by Yakuji Nippo), “Japan Those described in “Pharmacopeia” (published by Yodogawa Shoten) and “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo) can be used.
Further, they may be subjected to processing such as coating and liposome formation for various purposes. These constituent components may be used alone or in combination. The agent for preventing or improving lifestyle-related diseases of the present invention can be processed by known methods such as dissolution, mixing, dispersion, granulation, melting / solidification, compression, and drying.
以下に、本発明のセロオリゴ糖を有効成分とする生活習慣病予防または改善剤と、食品素材、化粧品素材、医薬品薬効成分、またはそれらで使用される添加物の中から選択される1種以上の構成成分を含む食品または医薬品の製造方法について記述するが、本発明生活習慣病予防/改善剤の製造方法は、以下の方法に制限されるものではない。 The lifestyle-related disease prevention or improvement agent which uses the cellooligosaccharide of this invention as an active ingredient below, and 1 or more types selected from a food material, a cosmetic material, a pharmaceutical active ingredient, or an additive used therewith Although the manufacturing method of the foodstuff or pharmaceutical containing a structural component is described, the manufacturing method of the lifestyle-related disease prevention / amelioration agent of this invention is not restrict | limited to the following method.
各成分の添加方法は、通常行われている方法であれば特に制限はないが、1)セロオリゴ糖と構成成分を同時に添加し、混合または分散しても、2)セロオリゴ糖と特定の構成成分を予め混合または分散した後に、別の構成成分を添加し、混合または分散しても、3)2種以上の構成成分を予め混合または分散した後、セロオリゴ糖を添加し、混合または分散しても、これらの添加方法を組み合わせた方法でもよい。 The method for adding each component is not particularly limited as long as it is a commonly used method, but 1) Cello-oligosaccharide and component may be added simultaneously and mixed or dispersed. 2) Cellooligosaccharide and specific component 3) After mixing or dispersing in advance, another component is added and mixed or dispersed. 3) After mixing or dispersing two or more components in advance, cellooligosaccharide is added and mixed or dispersed. Or a combination of these addition methods.
ここで用いる装置としては、小型吸引輸送装置、空気輸送装置、バケットコンベヤ、圧送式輸送装置、バキュームコンベヤ、振動式定量フィーダー、スプレー、漏斗等を用いて連続的に添加しても、一括投入してもよい。また、各成分の混合方法は、通常行われている方法であれば特に制限はないが、V型、W型、ダブルコーン型、コンテナタック型混合機などの容器回転式混合機、あるいは高速撹拌型、万能撹拌型、リボン型、パグ型、ナウター型混合機などの撹拌式混合機、高速流動式混合機、ドラム式混合機、流動層式混合機を使用してもよい。またシェーカー等の容器振とう式混合機を使用することもできる。 The devices used here are small suction transport devices, pneumatic transport devices, bucket conveyors, pressure-feed transport devices, vacuum conveyors, vibratory quantitative feeders, sprays, funnels, etc. May be. The mixing method of each component is not particularly limited as long as it is a normal method, but a container rotary mixer such as a V type, W type, double cone type, container tack type mixer, or high-speed stirring is used. A stirring mixer such as a mold, a universal stirring type, a ribbon type, a pug type, and a Nauta type mixer, a high-speed fluid mixer, a drum mixer, and a fluidized bed mixer may be used. A shaker mixer such as a shaker can also be used.
分散方法としては、通常行われる分散方法であれば特に制限はないが、ポータブルミキサー、立体ミキサー、側面ミキサーなどの1方向回転式、多軸回転式、往復反転式、上下移動式、回転+上下移動式、管路式等の撹拌翼を使用する撹拌混合方法、ラインミキサー等の噴流式撹拌混合方法、気体吹き込み式の撹拌混合方法、高剪断ホモジナイザー、高圧ホモジナイザー、超音波ホモジナイザー等を使用する混合方法でも、シェーカーを使用する容器振とう式混合方法等を用いてもよく、これらを組み合わせた方法でもよい。 The dispersion method is not particularly limited as long as it is a commonly performed dispersion method, but it is a one-way rotation type such as a portable mixer, a three-dimensional mixer, a side mixer, a multi-axis rotation type, a reciprocating reversal type, a vertical movement type, a rotation + up and down Mixing method using stirring blades such as mobile type, pipe type, jet type stirring and mixing method such as line mixer, gas blowing type stirring and mixing method, high shear homogenizer, high pressure homogenizer, ultrasonic homogenizer, etc. The method may also be a container-shaking mixing method using a shaker, or a combination of these methods.
また、上述の混合、分散において、水又は有機溶剤に、必要に応じて界面活性剤、増粘剤、ゲル化剤を添加した水系媒体を添加する順序には特に制限はないが、1)セロオリゴ糖に予め水系媒体を添加し、溶解または分散させた後に、他の構成成分を添加しても、2)構成成分に予め水系媒体を添加し、溶解または分散させた後に、セロオリゴ糖を添加しても、3)セロオリゴ糖と構成成分を予め混合または分散させた後に、水系媒体を添加してもよく、これらを組み合わせた方法でもよい。ここで得られた水溶液、分散体、乳液等の各液状、ペースト、ゲル等の各半固形状の食品または医薬品は、必要に応じて乾燥し、造粒、コーティング、成型等の加工を施してもよい。 Further, in the above mixing and dispersion, there is no particular limitation on the order of adding an aqueous medium to which a surfactant, a thickener, or a gelling agent is added as necessary to water or an organic solvent. Even if other components are added after the aqueous medium is added to the sugar in advance and dissolved or dispersed, 2) the cellooligosaccharide is added after the aqueous medium is added to the constituent in advance and dissolved or dispersed. Alternatively, 3) an aqueous medium may be added after the cellooligosaccharide and the constituent components are mixed or dispersed in advance, or a combination of these may be used. Each liquid, such as aqueous solution, dispersion, and emulsion obtained here, or each semi-solid food or medicine such as paste, gel, etc., is dried and subjected to processing such as granulation, coating, molding, etc. as necessary. Also good.
造粒・コーティング方法としては、公知の方法であれば特に制限はないが、攪拌式または流動層式のいずれもよく、それらを組み合わせた方法でもよい。攪拌式造粒機としては、例えばポータブルミキサー、立体ミキサー、側面ミキサーなどの1方向回転式、多軸回転式、往復反転式、上下移動式、回転+上下移動式の攪拌機、流動層式としては上部噴霧式、中央噴霧式、下部噴霧式、攪拌併用式、中央缶噴流式、ワースター式等が挙げられる。また、ローラーコンパクタを使用した乾式造粒を施してもよい。 The granulation / coating method is not particularly limited as long as it is a known method, but either a stirring method or a fluidized bed method may be used, or a method combining them may be used. Examples of the agitation granulator include a one-way rotary type such as a portable mixer, a three-dimensional mixer, and a side mixer, a multi-axis rotary type, a reciprocating reversal type, a vertical movement type, a rotation + vertical movement type agitator, and a fluidized bed type. An upper spray type, a central spray type, a lower spray type, a combined stirring type, a central can jet type, a Wurster type and the like can be mentioned. Moreover, you may give the dry granulation which uses a roller compactor.
コーティングについては、予め造粒物を得、それに公知のコーティングを施してもよく、コーティングを施した後、さらに別のコーティングを施し多層状としてもよい。コーティング剤の噴霧方法としては、圧力ノズル、二流体ノズル、四流体ノズル、回転ディスク、超音波ノズル等を使用し活性成分溶液または分散液を噴霧する方法、管状ノズルから活性成分溶液または分散液を滴下する方法のいずれでもよい。活性成分溶液または分散液を添加する際には、セロオリゴ糖粒子表面に活性成分を積層させるようなレイヤリング、コーティングを施しても、セロオリゴ糖に担持させてもよく、構成成分溶液または分散液を結合液としてセロオリゴ糖と他の構成成分の混合物をマトリックス状に造粒させてもよい。レイヤリング、コーティングは湿式であっても、乾式であっても効果は同様である。 Regarding the coating, a granulated product may be obtained in advance, and a known coating may be applied thereto, or after coating, another coating may be applied to form a multilayer. As a spraying method of the coating agent, a method of spraying an active ingredient solution or dispersion using a pressure nozzle, a two-fluid nozzle, a four-fluid nozzle, a rotating disk, an ultrasonic nozzle, etc., and an active ingredient solution or dispersion from a tubular nozzle are used. Any method of dropping may be used. When the active ingredient solution or dispersion is added, the active ingredient may be layered or coated so as to be laminated on the surface of the cellooligosaccharide particles, or may be supported on the cellooligosaccharide. As a binding solution, a mixture of cellooligosaccharide and other components may be granulated in a matrix. The effect is the same whether the layering or coating is wet or dry.
成型方法としては、通常行われている方法であれば特に制限はないが、型枠を用いてもよく、圧縮、溶融、射出、圧延等の公知の成型方法が適用でき、これらを組み合わせた方法でもよい。ここで用いられる成型機としては、圧縮成型機、溶融成型機、射出成型機、圧延成型機等が挙げられ、製菓用または化粧品または医薬品用成型機、米飯成型機、コンプレスド成型機、包あん機、蒲鉾製造装置、餃子・包子成型機、ファンデーション基材用圧縮成型機等の公知の成型機が使用できる。特に圧縮成型に関しては、型枠を使用し所望の形状に圧縮成形する方法、予めシート状に圧縮成形した後所望の形状に割断する方法でもよい。圧縮成形機としては、例えば、静圧プレス機、ブリケッティングローラー型プレス機、平滑ローラー型プレス機等のローラー式プレス機、シングルパンチ打錠機、ロータリー打錠機等の圧縮機を使用できる。 The molding method is not particularly limited as long as it is a commonly performed method, but a mold may be used, and a known molding method such as compression, melting, injection, rolling, etc. can be applied, and a method combining these But you can. Examples of molding machines used here include compression molding machines, melt molding machines, injection molding machines, rolling molding machines, etc., confectionery or cosmetic or pharmaceutical molding machines, cooked rice molding machines, compressed molding machines, wrapping machines. Well-known molding machines, such as a rice cake manufacturing apparatus, a dumpling / wrapping molding machine, and a foundation substrate compression molding machine, can be used. In particular, regarding compression molding, a method of compression molding into a desired shape using a mold, or a method of pre-compressing into a sheet shape and then cleaving into a desired shape may be used. As the compression molding machine, for example, a roller press such as a hydrostatic press, a briquetting roller press, a smooth roller press, a compressor such as a single punch tablet press, or a rotary tablet press can be used. .
次に、上述の生活習慣病予防または改善剤の製造において使用される構成成分の一例を記す。
例えば、食品素材またはそこで使用される添加剤としては、本発明のセロオリゴ糖に加え、必要に応じて、保存料・日持向上剤、酸化防止剤、甘味料、着色料、乳化剤、増粘剤、品質改良剤、調味料、酸味料、強化剤、スパイス・ハーブ、食品香料、酵素等を添加してもよい。これらの食品素材または添加剤は、それを単独で使用しても、2種以上を併用することも自由である。
Next, an example of the component used in manufacture of the above-mentioned lifestyle-related disease prevention or improvement agent is described.
For example, food materials or additives used therein include, in addition to the cellooligosaccharides of the present invention, preservatives, shelf-life improvers, antioxidants, sweeteners, colorants, emulsifiers, thickeners as necessary. , Quality improvers, seasonings, acidulants, fortifiers, spices and herbs, food fragrances, enzymes and the like may be added. These food materials or additives can be used alone or in combination of two or more.
保存料・日持向上剤としては、例えば、ソルビン酸、ソルビン酸カリウム、安息香酸、安息香酸ナトリウム、パラオキシ安息香酸エステル、デヒドロ酢酸ナトリウム、プロピオン酸、プロピオン酸塩、酢酸、酢酸ナトリウム、グリシン、エチルアルコール、ポリリジン、プロタミン、リゾチーム、ペクチン分解物、アラニン、チアミンラウリル硫酸塩、ユッカフォーム抽出物、キトサン、プロピレングリコール等の「食品添加物公定書」(廣川書店発行)に保存料・日持向上剤として分類されるものが挙げられる。 Examples of preservatives and shelf-life improvers include sorbic acid, potassium sorbate, benzoic acid, sodium benzoate, p-hydroxybenzoate, sodium dehydroacetate, propionic acid, propionate, acetic acid, sodium acetate, glycine, ethyl Preservatives and longevity improvers in “Food Additive Official Documents” (published by Yodogawa Shoten) such as alcohol, polylysine, protamine, lysozyme, pectin degradation products, alanine, thiamine lauryl sulfate, yucca foam extract, chitosan, propylene glycol Can be classified.
酸化防止剤としては、例えば、ブチルヒドロキシアニソール、ブチルヒドロキシトルエン、ビタミンC、アスコルビン酸ナトリウム、エリソルビン酸、エリソルビン酸ナトリウム、ビタミンE等の「食品添加物公定書」(廣川書店発行)に酸化防止剤として分類されるものが挙げられる。 Antioxidants include, for example, “Food Additive Official Document” (published by Yodogawa Shoten) such as butylhydroxyanisole, butylhydroxytoluene, vitamin C, sodium ascorbate, erythorbic acid, sodium erythorbate, vitamin E, etc. Can be classified.
甘味料としては、例えば、サッカリン、甘草、ステビア、アスパルテーム、スクラロース、アセスルファムカリウム、果糖、パノース、トレハロース、キシリトール、エリスリトール、ソルビトール、ラクチトール、マルチトール、還元パラチノース、還元みずあめ、マンニトール、カップリングシュガー、フラクトオリゴ糖、ガラクトオリゴ糖、乳化オリゴ糖、ニゲロオリゴ糖、キシロオリゴ糖、マルトオリゴ糖、イソマルトオリゴ糖、大豆オリゴ糖、パラチノース、パラチノースオリゴ糖、ラフィノース等の「食品添加物公定書」(廣川書店発行)に甘味料として分類されるものが挙げられる。 Examples of the sweetener include saccharin, licorice, stevia, aspartame, sucralose, acesulfame potassium, fructose, panose, trehalose, xylitol, erythritol, sorbitol, lactitol, maltitol, reduced palatinose, reduced mizuame, mannitol, coupling sugar, Sweetened in “Food Additives Official Document” (published by Yodogawa Shoten) such as fructooligosaccharide, galactooligosaccharide, emulsified oligosaccharide, nigerooligosaccharide, xylo-oligosaccharide, malto-oligosaccharide, isomalto-oligosaccharide, soybean oligosaccharide, palatinose, palatinose oligosaccharide, raffinose Those classified as fees are listed.
着色料としては、例えば、赤色2号、赤色3号、赤色40号、赤色102号、赤色105号、赤色106号、黄色4号、黄色5号、青色1号、青色2号、赤色3号レーキ、赤色40号レーキ、黄色4号レーキ、黄色5号レーキ、青色1号レーキ、青色2号レーキ等の食用タール類、カロチン色素、アナトー色素、パプリカ色素、コチニール色素、クチナシ色素、ベニバナ色素、ベニコウジ色素、ビートレッド、アカネ色素、スピルリナ色素、アントシアニン色素、カラメル等の「食品添加物公定書」(廣川書店発行)に、着色料として分類されるものが挙げられる。 Examples of the colorant include Red No. 2, Red No. 3, Red No. 40, Red No. 102, Red No. 105, Red No. 106, Yellow No. 4, Yellow No. 5, Blue No. 1, Blue No. 2, Red No. 3 Rake, red 40 rake, yellow 4 rake, yellow 5 rake, blue 1 rake, blue 2 rake and other edible tars, carotene dye, anato dye, paprika dye, cochineal dye, gardenia dye, safflower dye, Examples include those classified as colorants in “Food Additive Official Documents” (published by Yodogawa Shoten) such as Benikouji dye, beet red, akane dye, spirulina dye, anthocyanin dye, and caramel.
乳化剤としては、例えば、グリセリン脂肪酸エステル、ショ糖脂肪酸エステル、ソルビタン脂肪酸エステル、プロピレングリコール脂肪酸エステル、サポニン、レシチン等の「食品添加物公定書」(廣川書店発行)に乳化剤として分類されるものが挙げられる。 Examples of the emulsifier include those classified as emulsifiers in “official food additives” (published by Yodogawa Shoten) such as glycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, saponin and lecithin. It is done.
増粘剤としては、例えば、グアーガム、ローカストビーンガム、カラギーナン、寒天、ペクチン、キサンタンガム、ジェランガム、アラビアガム、グルコマンナン、アルギン酸、サイリウムシードガム、ゼラチン、メチルセルロース、カードラン、結晶セルロース、カルボキシメチルセルロース、タマリンドガム、難消化性デキストリン等の「食品添加物公定書」(廣川書店発行)に増粘剤として分類されるものが挙げられる。 Examples of thickeners include guar gum, locust bean gum, carrageenan, agar, pectin, xanthan gum, gellan gum, gum arabic, glucomannan, alginic acid, psyllium gum, gelatin, methylcellulose, curdlan, crystalline cellulose, carboxymethylcellulose, tamarind Examples include those classified as thickeners in the “Food Additives Official Document” (published by Yodogawa Shoten) such as gums and indigestible dextrins.
品質改良剤としては、大豆蛋白質、小麦蛋白質、カゼイン、カゼイネート、乳タンパク濃縮物、乳糖、リン酸塩等の「食品添加物公定書」(廣川書店発行)に品質改良剤として分類されるものが挙げられる。 As quality improvers, those classified as quality improvers in the “Food Additives Official Statement” (published by Yodogawa Shoten) such as soy protein, wheat protein, casein, caseinate, milk protein concentrate, lactose, phosphate, etc. Can be mentioned.
調味料としては、例えば、グルタミン酸ソーダ、核酸系調味料、畜産エキス、水産系エキス、野菜エキス、酵母エキス、アミノ酸系調味料、魚醤調味料、コク味調味料、シーズニングオイル等の「食品添加物公定書」(廣川書店発行)に調味料として分類されるものが挙げられる。 Examples of seasonings include sodium glutamate, nucleic acid seasonings, livestock extracts, marine extracts, vegetable extracts, yeast extracts, amino acid seasonings, fish sauce seasonings, kokumi seasonings, seasoning oils, etc. Those that are classified as seasonings in the “Kokusho Kosyo” (published by Yodogawa Shoten) are listed.
酸味料としては、例えば、クエン酸、乳酸、リンゴ酸、酒石酸、フマル酸、コハク酸、アジピン酸、グルコン酸等の「食品添加物公定書」(廣川書店発行)に酸味料として分類されるものが挙げられる。 As acidulants, for example, those classified as acidulants in the “Food Additive Official Document” (published by Yodogawa Shoten) such as citric acid, lactic acid, malic acid, tartaric acid, fumaric acid, succinic acid, adipic acid, gluconic acid, etc. Is mentioned.
強化剤としては、例えば、ビタミンA、ビタミンB群、ビタミンD、ビタミンK、カロチノイド、牛骨カルシウム、卵殻カルシウム、炭酸カルシウム、真珠貝、真珠末、蛎殻、ホタテ貝殻カルシウム、珊瑚末、魚骨末、ドロマイト、塩化マグネシウム、酵母ミネラル、ヘム鉄、深層水、塩水湖水ミネラル、海草・植物由来ミネラル等の「食品添加物公定書」(廣川書店発行)に強化剤として分類されるものが挙げられる。 Examples of the reinforcing agent include vitamin A, vitamin B group, vitamin D, vitamin K, carotenoid, beef bone calcium, eggshell calcium, calcium carbonate, pearl shell, pearl powder, rice husk, scallop shell calcium, powder powder, fish bone Powders, dolomite, magnesium chloride, yeast minerals, heme iron, deep water, saltwater lake minerals, seaweed / plant-derived minerals, etc. classified as fortifiers (issued by Yodogawa Shoten) .
スパイス・ハーブとしては、例えば、胡椒、唐辛子、ピメンタ、バニラ豆、桂皮、丁子、肉くず、肉くずの花、カルダモン、アニス・大ウイキョウ、コリアンダー、クミン、カラウェイ、ういきょう・ジュニパー、しょうが、サフラン、うこん、ローレル・タイム、カレー等の「食品添加物公定書」(廣川書店発行)にスパイス・ハーブとして分類されるものが挙げられる。 Examples of spices and herbs include pepper, chili, pimenta, vanilla beans, cinnamon bark, clove, meat scraps, meat scrap flowers, cardamom, anise and large fennel, coriander, cumin, caraway, seaweed, juniper, ginger, saffron , Ukon, Laurel Time, Curry, etc., which are classified as spices and herbs in the “Food Additives Official Document” (published by Yodogawa Shoten).
食用香料としては、例えば、ピーチフレーバー、オレンジフレーバー、レモンフレーバー等のフルーツフレーバー類、アロマフレーバー類、マルトール、フラネオール等のシュガーフレーバー類、ソトロン等のフレーバーエンハンサー類、フラボノイド類、カカオマス等のポリフェノール類、プリカーサーフレーバー類、ミートフレーバー類、コーヒーフレーバー類、ミルクフレーバー、メントール類、デカラクトン類等の「食品添加物公定書」(廣川書店発行)に食用香料として分類されるものが挙げられる。 Examples of edible flavors include fruit flavors such as peach flavor, orange flavor, and lemon flavor, aroma flavors, sugar flavors such as maltol and furaneol, flavor enhancers such as sotron, polyphenols such as flavonoids and cacao mass, Examples include those classified as edible fragrances in the “Food Additive Official Document” (published by Yodogawa Shoten), such as precursor flavors, meat flavors, coffee flavors, milk flavors, menthols, and decalactones.
酵素としては、例えば、α−アミラーゼ、β−アミラーゼ、グルコースイソメラーゼ、プロテアーゼ、レンネット、パンクレアチン、パパイン、リパーゼ、セルラーゼ、ブロメライン、ペクチナーゼ、リゾチーム、ヘスペリジナーゼ、プルラナーゼ、トランスグルタミナーゼ、ヘミセルラーゼ、β−ガラクタナーゼ、ラクターゼ、デキストラナーゼ、インベルターゼ、カタラーゼ、デアミナーゼ、ウレアーゼ、タンナーゼ、リポキシゲナーゼ、アデニルアミナーゼ等の「食品添加物公定書」(廣川書店発行)に酵素として分類されるものが挙げられる。 Examples of the enzyme include α-amylase, β-amylase, glucose isomerase, protease, rennet, pancreatin, papain, lipase, cellulase, bromelain, pectinase, lysozyme, hesperidinase, pullulanase, transglutaminase, hemicellulase, β-galacta Examples include those classified as enzymes in the “Food Additives Official Document” (published by Yodogawa Shoten), such as ase, lactase, dextranase, invertase, catalase, deaminase, urease, tannase, lipoxygenase, and adenylaminase.
次に、医薬品薬効成分またはそれらで使用される添加剤の一例を示す。
医薬品薬効成分としては、例えば、解熱鎮痛消炎薬、催眠鎮静薬、眠気防止薬、鎮暈薬、小児鎮痛薬、健胃薬、制酸薬、消化薬、強心薬、不整脈用薬、降圧薬、血管拡張薬、利尿薬、抗潰瘍薬、整腸薬、骨粗鬆症治療薬、鎮咳去痰薬、抗喘息薬、抗菌剤、頻尿改善剤、滋養強壮剤、ビタミン剤など、経皮または経口で投与されるものが対象となる。薬効成分は、それを単独で使用しても、2種以上を併用することも自由である。
また、医薬品で使用される添加剤としては、例えば、賦形剤、崩壊剤、結合剤、流動化剤、滑沢剤、矯味剤、香料、着色剤、甘味剤、溶剤、油脂、増粘剤、界面活性剤、ゲル化剤等があり、これらは、単独で使用しても、2種以上を併用することも自由である。
Next, an example of a medicinal medicinal ingredient or an additive used in them is shown.
Examples of medicinal medicinal ingredients include antipyretic analgesic / anti-inflammatory drugs, hypnotic sedatives, drowsiness preventives, antipruritics, pediatric analgesics, stomachic drugs, antacids, digestives, cardiotonic drugs, arrhythmic drugs, antihypertensive drugs, vasodilators Drugs, diuretics, anti-ulcer drugs, intestinal adjusters, osteoporosis drugs, antitussive expectorants, anti-asthma drugs, antibacterial agents, frequent urination improvers, nourishing tonics, vitamins, etc. Is the target. The medicinal component can be used alone or in combination of two or more.
Examples of additives used in pharmaceuticals include excipients, disintegrants, binders, fluidizers, lubricants, corrigents, fragrances, colorants, sweeteners, solvents, fats and oils, and thickeners. , Surfactants, gelling agents, and the like. These can be used alone or in combination of two or more.
賦形剤としては、アクリル酸デンプン、L−アスパラギン酸、アミノエチルスルホン酸、アミノ酢酸、あめ(粉)、アラビアゴム、アラビアゴム末、アルギン酸、アルギン酸ナトリウム、アルファー化デンプン、イノシトール、エチルセルロース、エチレン・酢酸ビニルコポリマー、塩化ナトリウム、オリーブ油、カオリン、カカオ脂、カゼイン、果糖、軽石粒、カルメロース、カルメロースナトリウム、含水二酸化ケイ素、乾燥酵母、乾燥水酸化アルミニウムゲル、乾燥硫酸ナトリウム、乾燥硫酸マグネシウム、カンテン、カンテン末、キシリトール、クエン酸、クエン酸ナトリウム、クエン酸二ナトリウム、グリセリン、グリセロリン酸カルシウム、グルコン酸ナトリウム、L−グルタミン、クレー、クレー粒、クロスカルメロースナトリウム、クロスポリビニルピロリドン、ケイ酸アルミン酸マグネシウム、ケイ酸カルシウム、ケイ酸マグネシウム、軽質無水ケイ酸、軽質流動パラフィン、ケイヒ末、結晶セルロース、結晶セルロース・カルメロースナトリウム、結晶セルロース(粒)、ゲンマイコウジ、合成ケイ酸アルミニウム、合成ヒドロタルサイト、ゴマ油、小麦粉、コムギデンプン、小麦胚芽粉、コメコ、コメデンプン、酢酸カリウム、酢酸カルシウム、酢酸フタル酸セルロース、サフラワー油、サラシミツロウ、酸化亜鉛、酸化チタン、酸化マグネシウム、β―シクロデキストリン、ジヒドロキシアルミニウムアミノアセテート、2,6−ジ−ブチル−4−メチルフェノール、ジメチルポリシロキサン、酒石酸、酒石酸水素カリウム、焼セッコウ、ショ糖脂肪酸エステル、水酸化アルミナマグネシウム、水酸化アルミニウム・ゲル、水酸化アルミニウム・炭酸水素ナトリウム共沈物、水酸化マグネシウム、スクラワン、ステアリルアルコール、ステアリン酸、ステアリン酸カルシウム、ステアリン酸ポリオキシル、ステアリン酸マグネシウム、ステロテックスHM、精製ゼラチン、精製セラック、精製白糖、精製白糖球状顆粒、セトステアリルアルコール、セトポリエチレングリコール、ゼラチン、ソルビタン脂肪酸エステル、D−ソルビトール、第三リン酸カルシウム、ダイズ油、大豆不ケン化物、大豆レシチン、脱脂粉乳、タルク、炭酸アンモニウム、炭酸カルシウム、炭酸マグネシウム、中性無水硫酸ナトリウム、低置換度ヒドロキシプロピルセルロース、デキストラン、デキストリン、天然ケイ酸アルミニウム、トウモロコシデンプン、トラガント末、二酸化ケイ素、乳酸カルシウム、乳糖、白色ワセリン、白糖、白糖・デンプン球状顆粒、ハダカムギ緑葉エキス末、裸麦芽葉青汁乾燥粉末、ハチミツ、パラフィン、バレイショデンプン、半消化体デンプン、人血清アルブミン、ヒドロキシプロピルスターチ、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロースフタレート、フィチン酸、ブドウ糖、ブドウ糖水和物、部分アルファー化デンプン、プルラン、プロピレングリコール、粉末還元麦芽糖水飴、粉末セルロース、ペクチン、ベントナイト、ポリアクリル酸ナトリウム、ポリオキシエチレンアルキルエーテル、ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンポリオキシプロピレングリコール、ポリスチレンスルホン酸ナトリウム、ポリビニルアセタールジエチルアミノアセテート、ポリエチレングリコール、マルチトール、マルトース、D−マンニトール、水アメ、ミリスチン酸イソプロピル、無水乳糖、無水リン酸水素カルシウム、無水リン酸カルシウム造粒物、メタケイ酸アルミン酸マグネシウム、メチルセルロース、綿実粉、綿実油、モクロウ、モノステアリン酸アルミニウム、モノステアリン酸グリセリン、モノステアリン酸ソルビタン、薬用炭、ラッカセイ油、硫酸アルミニウム、硫酸カルシウム、粒状トウモトコシデンプン、流動パラフィン、dl−リンゴ酸、リン酸−水素カルシウム、リン酸水素カルシウム、リン酸水素カルシウム造粒物、リン酸水素ナトリウム、リン酸二水素カリウム、リン酸二水素カルシウム、リン酸二水素ナトリウム等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に賦形剤として分類されるものが挙げられ、それを単独で使用しても、2種以上を併用することも自由である。 Excipients include starch acrylate, L-aspartic acid, aminoethylsulfonic acid, aminoacetic acid, candy (powder), gum arabic, gum arabic powder, alginic acid, sodium alginate, pregelatinized starch, inositol, ethylcellulose, ethylene Vinyl acetate copolymer, sodium chloride, olive oil, kaolin, cacao butter, casein, fructose, pumice grains, carmellose, carmellose sodium, hydrous silicon dioxide, dry yeast, dry aluminum hydroxide gel, dry sodium sulfate, dry magnesium sulfate, agar, Agar powder, xylitol, citric acid, sodium citrate, disodium citrate, glycerin, calcium glycerophosphate, sodium gluconate, L-glutamine, clay, clay granules, croscarmellose nato Um, cross polyvinyl pyrrolidone, magnesium aluminate silicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, cinnamon powder, crystalline cellulose, crystalline cellulose / carmellose sodium, crystalline cellulose (grain) , Synthetic aluminum silicate, synthetic hydrotalcite, sesame oil, wheat flour, wheat starch, wheat germ powder, rice, rice starch, potassium acetate, calcium acetate, cellulose acetate phthalate, safflower oil, white beeswax, zinc oxide, titanium oxide , Magnesium oxide, β-cyclodextrin, dihydroxyaluminum aminoacetate, 2,6-di-butyl-4-methylphenol, dimethylpolysiloxane, tartaric acid, potassium hydrogen tartrate, baked gypsum, sucrose fatty acid ester Tellurium Magnesium Hydroxide, Aluminum Hydroxide / Gel, Aluminum Hydroxide / Sodium Bicarbonate Coprecipitate, Magnesium Hydroxide, Suclan, Stearyl Alcohol, Stearic Acid, Calcium Stearate, Polyoxyl Stearate, Magnesium Stearate, Sterotex HM , Purified gelatin, purified shellac, purified sucrose, purified sucrose spherical granules, cetostearyl alcohol, cetopolyethylene glycol, gelatin, sorbitan fatty acid ester, D-sorbitol, tricalcium phosphate, soybean oil, soybean unsaponifiable matter, soybean lecithin, skim milk powder , Talc, ammonium carbonate, calcium carbonate, magnesium carbonate, neutral anhydrous sodium sulfate, low-substituted hydroxypropyl cellulose, dextran, dextrin, natural silicic acid Luminium, corn starch, tragacanth powder, silicon dioxide, calcium lactate, lactose, white petrolatum, sucrose, sucrose / starch spherical granules, powdered green leaf extract, naked malt green juice dry powder, honey, paraffin, potato starch, semi-digested body Starch, human serum albumin, hydroxypropyl starch, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, phytic acid, glucose, glucose hydrate, partially pregelatinized starch, pullulan, propylene glycol, powdered reduced maltose starch syrup, powdered cellulose, pectin, bentonite , Sodium polyacrylate, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polystyrene Sodium sulfonate, polyvinyl acetal diethylaminoacetate, polyethylene glycol, maltitol, maltose, D-mannitol, water candy, isopropyl myristate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate granule, magnesium aluminate metasilicate, methylcellulose , Cottonseed powder, cottonseed oil, owl, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, medicinal charcoal, peanut oil, aluminum sulfate, calcium sulfate, granular corn starch, liquid paraffin, dl-malic acid, phosphorus Acid-hydrogen calcium, calcium hydrogen phosphate, calcium hydrogen phosphate granules, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, phosphoric acid diwater Examples include sodium categorized as excipients in Japanese Pharmacopoeia (published by Yodogawa Shoten) and Pharmaceutical Additives Encyclopedia (published by Yakuji Nippo Co., Ltd.). In addition, two or more kinds can be used in combination.
崩壊剤としては、クロスカルメロースナトリウム、カルメロース、カルメロースカルシウム、カルメロースナトリウム、低置換度ヒドロキシプロピルセルロース等のセルロース類、カルボキシメチルスターチナトリウム、ヒドロキシプロピルスターチ、コメデンプン、コムギデンプン、トウモロコシデンプン、バレイショデンプン、部分アルファー化デンプン等のデンプン類、クロスポリビニルピロリドン、クロスポリビニルピロリドンコポリマー等の合成高分子等の「日本薬局方」(廣川書店発行)、「医薬品添加物事典」(薬事日報社(株)発行)に崩壊剤として分類されるものを挙げることができる。上記から選ばれる1種を単独で使用しても、2種以上を併用することも自由である。 Disintegrants include croscarmellose sodium, carmellose, carmellose calcium, carmellose sodium, celluloses such as low-substituted hydroxypropylcellulose, carboxymethyl starch sodium, hydroxypropyl starch, rice starch, wheat starch, corn starch, potato “Nippon Pharmacopoeia” (published by Yodogawa Shoten) such as starches, starches such as partially pregelatinized starch, synthetic polymers such as cross polyvinyl pyrrolidone and cross polyvinyl pyrrolidone copolymer, “Pharmaceutical additives encyclopedia” (Pharmaceutical Daily Inc.) Issued) is classified as a disintegrant. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
結合剤としては、白糖、ブドウ糖、乳糖、果糖等の糖類、マンニトール、キシリトール、マルチトール、エリスリトール、ソルビトール等の糖アルコール類、ゼラチン、プルラン、カラギーナン、ローカストビーンガム、寒天、グルコナンナン、キサンタンガム、タマリンドガム、ペクチン、アルギン酸ナトリウム、アラビアガム等の水溶性多糖類、結晶セルロース、粉末セルロース、ヒドロキシプロピルセルロース、メチルセルロース等のセルロース類、アルファー化デンプン、デンプン糊等のデンプン類、ポリビニルピロリドン、カルボキシビニルポリマー、ポリビニルアルコール等の合成高分子類、リン酸水素カルシウム、炭酸カルシウム、合成ヒドロタルサイト、ケイ酸アルミン酸マグネシウム等の無機化合物類等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に結合剤として分類されるものを挙げることができる。上記から選ばれる1種を単独で使用しても、2種以上を併用することも自由である。 As binders, sugars such as sucrose, glucose, lactose, fructose, sugar alcohols such as mannitol, xylitol, maltitol, erythritol, sorbitol, gelatin, pullulan, carrageenan, locust bean gum, agar, gluconannan, xanthan gum, tamarind Water-soluble polysaccharides such as gum, pectin, sodium alginate, gum arabic, etc., celluloses such as crystalline cellulose, powdered cellulose, hydroxypropylcellulose, methylcellulose, starches such as pregelatinized starch, starch paste, polyvinylpyrrolidone, carboxyvinyl polymer, "Japanese Pharmacopoeia" such as synthetic polymers such as polyvinyl alcohol, inorganic compounds such as calcium hydrogen phosphate, calcium carbonate, synthetic hydrotalcite, magnesium aluminate silicate, etc. Hirokawa Shoten) include those classified as a binder "Pharmaceutical additives Dictionary" (Yakujinipposha Corporation published). Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
流動化剤としては、含水二酸化ケイ素、軽質無水ケイ酸等のケイ素化合物類等の「医薬品添加剤事典」(薬事日報社(株)発行)に流動化剤として分類されるものを挙げることができる。上記から選ばれる1種を単独で使用しても、2種以上を併用することも自由である。 Examples of the fluidizing agent include those classified as fluidizing agents in the “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) such as silicon compounds such as hydrous silicon dioxide and light anhydrous silicic acid. . Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
滑沢剤としては、ステアリン酸マグネシウム、ステアリン酸カルシウム、ステアリン酸、ショ糖脂肪酸エステル、タルク等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に滑沢剤として分類されるものを挙げることができる。上記から選ばれる1種を単独で使用しても、2種以上を併用することも自由である。 Lubricants include magnesium stearate, calcium stearate, stearic acid, sucrose fatty acid ester, talc, etc. “Japan Pharmacopoeia” (published by Yodogawa Shoten), “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) And those classified as lubricants. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
矯味剤としては、グルタミン酸、フマル酸、コハク酸、クエン酸、クエン酸ナトリウム、酒石酸、リンゴ酸、アスコルビン酸、塩化ナトリウム、1−メントール等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に矯味剤として分類されるものを挙げることができる。上記から選ばれる1種を単独で使用しても、2種以上を併用することも自由である。 As a corrigent, glutamic acid, fumaric acid, succinic acid, citric acid, sodium citrate, tartaric acid, malic acid, ascorbic acid, sodium chloride, 1-menthol and other "Japanese Pharmacopoeia" (published by Yodogawa Shoten), What is classified as a corrigent in “Pharmaceuticals” (published by Yakuji Nippo Co., Ltd.) can be mentioned. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
香料としては、オレンジ、バニラ、ストロベリー、ヨーグルト、メントール、ウイキョウ油、ケイヒ油、トウヒ油、ハッカ油等の油類、緑茶末等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に着香剤、香料として分類されるものを挙げることができる。上記から選ばれる1種を単独で使用しても、2種以上を併用することも自由である。 Perfumes include orange, vanilla, strawberry, yogurt, menthol, fennel oil, cinnamon oil, spruce oil, mint oil, and other Japanese pharmacopoeia (published by Yodogawa Shoten) "(Published by Yakuji Nippo Co., Ltd.)" can be listed as flavoring agents and fragrances. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
着色剤としては、食用赤色3号、食用黄色5号、食用青色1号等の食用色素、銅クロロフィンナトリウム、酸化チタン、リボフラビン等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に着色剤として分類されるものを挙げることができる。上記から選ばれる1種を単独で使用しても、2種以上を併用することも自由である。 Coloring agents include food colors such as Food Red No. 3, Food Yellow No. 5, Food Blue No. 1, etc., "Japan Pharmacopoeia" (published by Yodogawa Shoten), such as copper chlorofin sodium, titanium oxide, and riboflavin. What is classified as a colorant in “Encyclopedia” (published by Yakuji Nippo Co., Ltd.) can be mentioned. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
甘味剤としては、アスパルテーム、サッカリン、グリチルリチン酸二カリウム、ステビア、マルトース、マルチトール、水飴、アマチャ末等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に甘味剤として分類されるものを挙げることができる。上記から選ばれる1種を単独で使用しても、2種以上を併用することも自由である。 Sweeteners include aspartame, saccharin, dipotassium glycyrrhizinate, stevia, maltose, maltitol, starch syrup, and amacha powder, etc., “Pharmaceutical Additives Encyclopedia” (Yakuji Nippo Inc.) ) Issue)) can be listed as sweeteners. Even if it uses individually by 1 type chosen from the above, it is also free to use 2 or more types together.
溶剤としては、医薬品に使用されるものであれば、特に制限されるものではないが、例えばメタノール、エタノールなどのアルコール類、アセトンなどのケトン類等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に溶剤として分類されるものが挙げられ、それを単独で使用しても、2種以上を併用することも自由である。 Solvents are not particularly limited as long as they are used in pharmaceuticals. For example, “Japan Pharmacopoeia” (published by Yodogawa Shoten) such as alcohols such as methanol and ethanol, and ketones such as acetone, Examples include those classified as solvents in the “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.), and they can be used alone or in combination of two or more.
油脂としては、例えば、ステアリン酸モノグリセリド、ステアリン酸トリグリセリド、ステア リン酸ショ糖エステル、流動パラフィン等のパラフィン類、カルナウバロウ,硬化ヒマシ油等の硬化油類、ヒマシ油、ステアリン酸、ステアリルアルコール、ポリエチレングリコール等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に記載される油脂が挙げられ、それを単独で使用しても、2種以上を併用することも自由である。 Examples of fats and oils include stearic acid monoglyceride, stearic acid triglyceride, stearic acid sucrose ester, paraffins such as liquid paraffin, hard oils such as carnauba wax and hardened castor oil, castor oil, stearic acid, stearyl alcohol, polyethylene glycol Such as “Japanese Pharmacopoeia” (published by Yodogawa Shoten) and “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.). They can also be used together.
増粘剤としては、例えば、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリアクリル酸、カルボキシビニルポリマー、ポリエチレングリコール、ポリビニルアルコール、ポリビニルピロリドン、メチルセルロース、エチルセルロース、アラビアゴム、デンプン糊等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に記載される増粘剤が挙げられ、それを単独で使用しても、2種以上を併用することも自由である。 As the thickener, for example, “Japanese Pharmacopoeia” such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, ethylcellulose, gum arabic, starch paste, etc. (Ayukawa Shoten)), “Thickeners” listed in “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.), which can be used alone or in combination of two or more. is there.
界面活性剤としては、例えば、リン脂質、グリセリン脂肪酸エステル、ポリエチレングリコール脂肪酸エステル、ソルビタン脂肪酸エステル、ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンセチルエーテル、ポリオキシエチレンステアリルエーテル、ポリオキシエチレンノニルフェニルエーテル、ポリオキシエチレンポリオキシプロピレングリコール、ポリオキシエチレンソルビタンサンモノラウレート、ポリソルベート、モノオレイン酸ソルビタン、モノステアリン酸グリセリド、モノオキシエチレンソルビタンモノパルミテート、モノオキシエチレンソルビタンモノステアレート、モノオレイン酸ポリオキシエチレンソルビタン、モノパルミチン酸ソルビタン、ラウリル硫酸ナトリウム等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)に界面活性剤として分類されるものが挙げられ、それを単独で使用しても、2種以上を併用することも自由である。 Examples of the surfactant include phospholipid, glycerin fatty acid ester, polyethylene glycol fatty acid ester, sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene cetyl ether, polyoxyethylene stearyl ether, polyoxyethylene nonylphenyl ether, Polyoxyethylene polyoxypropylene glycol, polyoxyethylene sorbitan sun monolaurate, polysorbate, sorbitan monooleate, glyceride monostearate, monooxyethylene sorbitan monopalmitate, monooxyethylene sorbitan monostearate, polyoxymonooleate "Japanese Pharmacopoeia" (published by Yodogawa Shoten), such as ethylene sorbitan, sorbitan monopalmitate, sodium lauryl sulfate, Those classified as surfactants listed chemicals additives Dictionary "(Yakujinipposha Corporation issued), the use of it alone, it is free to combination of two or more.
ゲル化剤としては、例えば、ゼラチン等の動物性ゲル化剤、寒天、キサンタンガム、グアーガム、アラビアガム、カードラン、ローカストビーンガム、カルボキシメチルセルロース、ヒドロキシエチルセルロース、セルロース、微結晶セルロース等植物性多糖類、ポリビニルピロリドン等の化学合成高分子等の「日本薬局方」(廣川書店発行)、「医薬品添加剤事典」(薬事日報社(株)発行)にゲル化剤として分類されるものが挙げられ、それを単独で使用しても、2種以上を併用することも自由である。 Examples of the gelling agent include animal gelling agents such as gelatin, vegetable polysaccharides such as agar, xanthan gum, guar gum, gum arabic, curdlan, locust bean gum, carboxymethylcellulose, hydroxyethylcellulose, cellulose, microcrystalline cellulose, Examples of chemically synthesized polymers such as polyvinylpyrrolidone that are classified as gelling agents in the “Japanese Pharmacopoeia” (published by Yodogawa Shoten) and “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo Co., Ltd.) Even if it uses singly, it is also free to use 2 or more types together.
本発明のセロオリゴ糖含有食品の例としては、例えば、ゼリー、プリン、ヨーグルト等のゲル、マヨネーズ、ドレッシング、ソース類、たれ類、スープ、野菜加工品等の調味料、カレー、ハヤシ、ミートソース、シチュー、スープ等のレトルト食品、チルド食品、ハンバーグ、ベーコン、ソーセージ、サラミソーセージ、ハム類等の畜産加工品、蒲鉾、ちくわ、魚肉ハム・ソーセージ、揚げ蒲鉾等の水練製品、パン、生麺、乾麺、マカロニ、スパゲッティ、中華饅頭の皮、ケーキミックス、プレミックス、ホワイトソース、餃子・春巻等の皮類などの小麦加工食品、カレー、ソース、スープ、佃煮、ジャムなどの缶詰、瓶詰類、キャンデー、トローチ、錠菓、チョコレート、ビスケット、クッキー、米菓、和洋菓子、洋生菓子、スナック菓子、砂糖菓子、プリンなどの菓子類、フライ類、コロッケ、餃子、中華饅頭等の調理加工品、野菜ペースト、肉のミンチ、果実ペースト、魚介類のペースト等のペースト類である。また、アイスクリーム、アイスミルク、ラクトアイス、ホイップクリーム、練乳、バター、ヨーグルト、チーズ、ホワイトソース等の乳製品、マーガリン、ファットスプレッド、ショートニング等の油脂加工品等がある。さらに、コーラ等の炭酸飲料、炭酸入り、アルコール入り、乳製品と混合した果実飲料、果汁又は、果実入り飲料、乳性飲料等の飲料、コーヒー、牛乳、豆乳、ココア牛乳、フルーツ牛乳、ヨーグルト等の乳酸または乳性飲料等、煎茶、ウーロン茶、抹茶、紅茶等の茶飲料等に使用してもよい。 Examples of the cellooligosaccharide-containing food of the present invention include, for example, gels such as jelly, pudding, and yogurt, mayonnaise, dressings, sauces, sauces, soups, processed vegetables and other seasonings, curry, hayashi, meat sauce, stew , Retort food such as soup, chilled food, hamburger, bacon, sausage, salami sausage, livestock processed products such as ham, rice cake, chikuwa, fish ham and sausage, fried rice cake such as fried rice cake, bread, raw noodles, dry noodles, Processed wheat foods such as macaroni, spaghetti, Chinese bun skin, cake mix, premix, white sauce, gyoza and spring rolls, canned curry, sauce, soup, boiled, jam, bottling, candy, Lozenges, tablet confectionery, chocolate, biscuits, cookies, rice confectionery, Japanese and Western confectionery, Western confectionery, snack confectionery Confectionery and sugar confectionery, puddings, fries, croquettes, dumplings, cooking processed products such as Chinese bun, vegetable paste, minced meat, fruit paste, a paste such as seafood paste. In addition, there are dairy products such as ice cream, ice milk, lact ice, whipped cream, condensed milk, butter, yogurt, cheese and white sauce, and processed oils and fats such as margarine, fat spread and shortening. In addition, carbonated drinks such as cola, carbonated drinks, alcohol drinks, fruit drinks mixed with dairy products, fruit juice or drinks containing fruits, milk drinks, coffee, milk, soy milk, cocoa milk, fruit milk, yogurt, etc. It may be used for tea beverages such as lactic acid or milk beverages, sencha, oolong tea, matcha tea, black tea and the like.
本発明のセロオリゴ糖含有医薬品の例としては、例えば、錠剤、散剤、細粒剤、顆粒剤、エキス剤、丸剤の固形製剤が挙げられ、上記の固形製剤以外でも、菓子、健康食品、食感改良剤、食物繊維強化剤等の食品、固形ファンデーション、浴用剤、動物薬、診断薬、農薬、肥料、セラミックス触媒等に利用されるものも本発明に含まれる。 Examples of the cellooligosaccharide-containing pharmaceutical of the present invention include, for example, solid preparations of tablets, powders, fine granules, granules, extracts, and pills. Other than the above solid preparations, confectionery, health food, food What is used for foodstuffs, such as a feeling improvement agent and a dietary fiber reinforcement | strengthening agent, solid foundation, a bath preparation, an animal medicine, a diagnostic agent, an agrochemical, a fertilizer, a ceramic catalyst, etc. is also contained in this invention.
本発明で用いるセロオリゴ糖は、腸内細菌叢改善、乳酸菌、乳酸かん菌等の活性化、血中糖濃度、血中インシュリン濃度の低減、血中コレステロールの低減、体脂肪率の低減、脂質・糖質代謝促進機能、便通・便臭改善、抗う触性等の各種生理活性が期待できるため、上記の通常食品用途に加え、生理活性物質として、機能性食品、健康食品、ダイエット食品等の用途で使用してもよい。 Cellooligosaccharides used in the present invention are improved intestinal flora, activation of lactic acid bacteria, lactobacilli, etc., blood sugar concentration, blood insulin concentration reduction, blood cholesterol reduction, body fat percentage reduction, lipid Various physiological activities such as carbohydrate metabolism-promoting function, bowel movement / stool odor improvement, anti-tactile properties, etc. can be expected. In addition to the above normal food applications, functional foods, health foods, diet foods, etc. May be used.
本発明を実施例に基づいて説明するが、本発明はこれらに限定されるものではない。
[製造例1]
普通寒天培地にトリコデルマ リーセイ(Tricoderma reesei)GL−1株(独立行政法人産業技術総合研究所 特許生物寄託センター、受領番号FERM ABP−10323)を接種し、37℃で7日間培養後、その培地表面から胞子を1白金耳取り、ポリペプトン1g、酵母エキス0.5g、リン酸1カリウム2g、硫酸アンモニウム1.5g、硫酸マグネシウム0.3g、塩化カルシウム0.3g、トレースエレメント1mL(硼酸6mg、モリブデン酸アンモニウム4水和物26mg、塩化鉄(3)6水和物100mg、硫酸銅5水和物40mg、硫酸マンガン4水和物8mg、硫酸亜鉛7水和物200mgを全量100mLの精製水に溶解させたもの)、アデカノール1mL、結晶セルロース(旭化成ケミカルズ製 商品名PH−101)10gを全量1Lの精製水に懸濁および溶解させた培地に植菌し、28℃で5日間通気攪拌培養した。培養中は、水酸化ナトリウム水溶液を用いて、培地のpHを2.8〜4.7となるように調節した。培養後の液を遠心分離し、上澄みを目開き0.46μmの精密ろ過膜で除菌し、ろ液を分画分子量13000の限外ろ過膜(旭化成ケミカルズ製 商品名マイクローザペンシル型モジュール ACP−0013)で体積比で10倍濃縮し粗酵素を得た。
The present invention will be described based on examples, but the present invention is not limited thereto.
[Production Example 1]
Trichoderma reesei GL-1 strain (Incorporated Administrative Agency, National Institute of Advanced Industrial Science and Technology, Patent Biodeposition Center, receipt number FERM ABP-10323) was inoculated on a normal agar medium, cultured at 37 ° C for 7 days, and then the surface of the medium 1 spore ears, 1 g polypeptone, 0.5 g yeast extract, 2 g potassium phosphate, 1.5 g ammonium sulfate, 0.3 g magnesium sulfate, 0.3 g calcium chloride, 1 mL trace element (6 mg boric acid, ammonium molybdate) 26 mg of tetrahydrate, 100 mg of iron chloride (3) hexahydrate, 40 mg of copper sulfate pentahydrate, 8 mg of manganese sulfate tetrahydrate, and 200 mg of zinc sulfate heptahydrate were dissolved in 100 mL of purified water in total. ), Adecanol 1 mL, crystalline cellulose (product of Asahi Kasei Chemicals) No. PH-101) was inoculated into a medium suspended and dissolved in 1 L of purified water in a total amount, and cultured with aeration and stirring at 28 ° C. for 5 days. During the culture, the pH of the medium was adjusted to 2.8 to 4.7 using an aqueous sodium hydroxide solution. The culture solution is centrifuged, the supernatant is sterilized with a microfiltration membrane having an opening of 0.46 μm, and the filtrate is ultrafiltered with a molecular weight cut off of 13,000 (trade name: Microza pencil type module ACP- manufactured by Asahi Kasei Chemicals). 0013) was concentrated 10 times by volume to obtain a crude enzyme.
次に、市販針葉樹由来の溶解パルプを使用し、加水分解条件を塩酸濃度0.4%塩酸水溶液、120℃、1時間として、加水分解し、酸不溶性残渣を洗浄、ろ過し、ウェットケークを得た。このウェットケークをセルロース10%濃度の水分散体とし、超高性能分散機・湿式微粉砕機(アシザワ(株)製、商品名 パールミルRL φ1mmジルコニアビーズ使用 充填率80%)を使用し、圧密・摩砕処理を施し、セルロース微粒子分散体を得た(平均重合度220、ジエチルエーテル可溶物含有率0.7%、平均粒子径0.7μm、コロイド状成分含有率51.5%)。
この摩砕セルロースが2質量%、粗酵素をタンパク質濃度0.25%になるように50mM酢酸−酢酸ナトリウム緩衝液(pH4.5)に懸濁溶解させ、全量1000mLとし、ガラス製フラスコに仕込んだ。このガラス製フラスコを、55℃の水槽に仕込み、内部を攪拌しながら4時間反応させた。反応終了後、反応液を懸濁状態で300μL分注し、限外ろ過モジュール(分画分子量10000)を使用し、酵素、未分解セルロースを取り除いた後、高速液体クロマトグラフィーで糖濃度を分析した。該反応液の糖濃度は、セロトリオース〜セロヘキサオース0.2質量%、セロビオース1.5質量%、グルコース0.3質量%であった。
該反応液を、分画分子量13000の限外ろ過膜(旭化成ケミカルズ製 商品名マイクローザペンシル型モジュール ACP−0013)でろ過し、得られたろ液を陽・陰イオン交換樹脂で脱イオン処理し、70℃、減圧下で蒸留し、20倍の糖濃度の水溶液を得た。
Next, use a commercially available softwood-derived dissolving pulp, and hydrolyze it with a hydrochloric acid concentration of 0.4% aqueous hydrochloric acid at 120 ° C. for 1 hour to wash the acid-insoluble residue and filter to obtain a wet cake. It was. Using this wet cake as an aqueous dispersion with a concentration of 10% cellulose, an ultra-high performance disperser / wet pulverizer (manufactured by Ashizawa Co., Ltd., trade name: Pearl Mill RL φ1mm zirconia bead filling rate 80%) A grinding treatment was performed to obtain a cellulose fine particle dispersion (average polymerization degree 220, diethyl ether soluble matter content 0.7%, average particle diameter 0.7 μm, colloidal component content 51.5%).
The ground cellulose was suspended and dissolved in a 50 mM acetic acid-sodium acetate buffer (pH 4.5) so that the crude cellulose was 2% by mass and the protein concentration was 0.25%, and the total volume was 1000 mL. . The glass flask was placed in a 55 ° C. water bath and reacted for 4 hours while stirring the interior. After completion of the reaction, 300 μL of the reaction solution was dispensed in a suspended state, the enzyme and undegraded cellulose were removed using an ultrafiltration module (fractional molecular weight 10,000), and then the sugar concentration was analyzed by high performance liquid chromatography. . The sugar concentration of the reaction solution was cellotriose to cellohexaose 0.2% by mass, cellobiose 1.5% by mass, and glucose 0.3% by mass.
The reaction solution was filtered through an ultrafiltration membrane having a molecular weight cut off of 13000 (trade name Micro-The Pencil type module ACP-0013 manufactured by Asahi Kasei Chemicals), and the resulting filtrate was deionized with a cation / anion exchange resin. Distillation was performed at 70 ° C. under reduced pressure to obtain an aqueous solution having a sugar concentration of 20 times.
[製造例2]
製造例1で得られたセロオリゴ糖水溶液100mLを、200mLのガラス製フラスコに導入し、攪拌しながら、毎時10℃の速度で、70℃から5℃まで冷却した。25℃で水溶液中に晶出したセロオリゴ糖を、減圧ろ過し、40℃の通風式乾燥機で乾燥し、乳鉢で粉砕後、目開き150μmの篩いで篩下し、篩下粉末を目開き45μmの篩いで微粉を除去し、セロオリゴ糖粉末CE−1を得た。得たれたセロオリゴ糖粉末の糖組成を表1に記す。
[Production Example 2]
100 mL of the cellooligosaccharide aqueous solution obtained in Production Example 1 was introduced into a 200 mL glass flask and cooled from 70 ° C. to 5 ° C. at a rate of 10 ° C. per hour while stirring. Cellooligosaccharide crystallized in an aqueous solution at 25 ° C. is filtered under reduced pressure, dried with a ventilating dryer at 40 ° C., pulverized in a mortar, and then sieved with a sieve having an opening of 150 μm, and the powder under the sieve is opened with an opening of 45 μm. The fine powder was removed using a sieve to obtain cellooligosaccharide powder CE-1. The sugar composition of the obtained cellooligosaccharide powder is shown in Table 1.
[製造例3]
製造例1の菌株を、セロビブリオ ギルバス(Cellovibrio gilvus)に代え、培養時のpHを4〜10に変更し、酵素反応時の緩衝液をpH6.5のリン酸緩衝液に変更する以外は、製造例1と同様の方法でセロオリゴ糖水溶液を作成した。
得られたセロオリゴ糖水溶液を、活性炭を充填したカラムに通して、セロビオースリッチの画分を除去し、製造例2と同様の操作でセロオリゴ糖粉末CE−2を得た。得たれたセロオリゴ糖粉末の糖組成を表1に記す。
[Production Example 3]
Manufacture except that the strain of Production Example 1 is replaced with Cellobibrio gilvus, the pH during culture is changed to 4-10, and the buffer during enzyme reaction is changed to a phosphate buffer of pH 6.5. A cellooligosaccharide aqueous solution was prepared in the same manner as in Example 1.
The obtained cellooligosaccharide aqueous solution was passed through a column filled with activated carbon to remove the cellobiose-rich fraction, and cellooligosaccharide powder CE-2 was obtained in the same manner as in Production Example 2. The sugar composition of the obtained cellooligosaccharide powder is shown in Table 1.
[製造例4]
製造例2のセロオリゴ糖の製造方法において、セロオリゴ糖水溶液に常温でエタノールを重量比で2.5倍加え、製造例1と同様に冷却晶析し、セロオリゴ糖粉末CE−3を得た。
[製造例5]
製造例3で得られたセロオリゴ糖水溶液を、そのまま噴霧乾燥(東京理化製 噴霧乾燥機 出口温度72℃)し、セロオリゴ糖粉末CE−4を得た。
[Production Example 4]
In the method for producing cellooligosaccharide of Production Example 2, ethanol was added 2.5 times by weight to the cellooligosaccharide aqueous solution at room temperature and cooled and crystallized in the same manner as in Production Example 1 to obtain cellooligosaccharide powder CE-3.
[Production Example 5]
The cellooligosaccharide aqueous solution obtained in Production Example 3 was directly spray-dried (Tokyo Rika spray dryer outlet temperature 72 ° C.) to obtain cellooligosaccharide powder CE-4.
<インスリン非上昇性についての確認試験>
生後7週齢のSDラットを1週間AIN−93G(オリエンタル酵母工業製)の自由摂取で、1週間予備飼育後、16時間絶食させ、表1の各セロオリゴ糖水溶液を、ゾンデを用いて1500mg/kgを投与した。投与前および投与後、30分後に無麻酔下で、骸外静脈より採血し、インスリン濃度(ng/mL シバヤギ製 レビインスリンキット使用)を測定した。インスリン濃度の上昇率は、CE−1〜3で30%未満であり、これらのセロオリゴ糖がインスリン非上昇性であることを確認した。
<Confirmation test for non-insulin elevation>
Seven-week-old SD rats were allowed free intake of AIN-93G (manufactured by Oriental Yeast Co., Ltd.) for 1 week, fasted for 1 week, fasted for 16 hours, and each cellooligosaccharide aqueous solution in Table 1 was 1500 mg / day using a sonde. kg was administered. Blood samples were collected from the extracorporeal vein under anesthesia before and 30 minutes after the administration, and the insulin concentration (ng / mL Shibayagi Levi insulin kit was used) was measured. The increase rate of insulin concentration was less than 30% in CE-1 to 3, and it was confirmed that these cellooligosaccharides are non-insulin increasing.
<自然発症2型糖尿病マウスにおける生活習慣病改善>
[実施例1〜3]
実験動物として、5週齢の雄KK−Ayマウス(日本クレア製 Ta/Jcl)を用いた。マウスは、個別のステンレスケージに入れて、室温23±5℃、湿度40〜70%、明暗各12時間(照明午前7時〜午後7時)、換気12回/時(フィルターにより除菌した新鮮空気)に維持された飼育室で動物を飼育した。
まず、5日間の予備飼育を行い、予備飼育中は、粉末飼料(CRF−1 オリエンタル酵母工業製)を給餌器に入れ、自由摂取させた。また、飲水として水道水を用い、飼育期間中は自由摂取させた。
予備飼育の後、コンピューターを用いた無作為法により、各群の群分け前の血糖値、体重がほぼ等しくなるように、1群10匹構成で群分けを行った。群分け後、粉末飼料を標準食(AIN−93G オリエンタル酵母工業製)に代え、同様に飼育した。セロオリゴ糖の添加効果は、上述の標準食中のショ糖を固定し、ショ糖以外の成分の内、2.5または5質量%を表1に示すCE−1〜3の各セロオリゴ糖粉末に代えて比較した。30日飼育および、60日飼育の結果を表2に示す。
<Improvement of lifestyle-related diseases in spontaneous type 2 diabetic mice>
[Examples 1 to 3]
As an experimental animal, a 5-week-old male KK- Ay mouse (Ta / Jcl manufactured by CLEA Japan) was used. Mice are placed in individual stainless steel cages, room temperature 23 ± 5 ° C., humidity 40-70%, light / dark 12 hours each (lighting 7 am-7pm), ventilation 12 times / hour (fresh sterilized by filter) Animals were raised in a breeding room maintained in air.
First, pre-breeding for 5 days was performed, and during the pre-breeding, powdered feed (CRF-1 Oriental Yeast Co., Ltd.) was placed in a feeder and allowed to freely take. In addition, tap water was used as drinking water and allowed to freely ingest during the breeding period.
After the preliminary breeding, the grouping was performed in a group of 10 animals so that the blood glucose level and the body weight before grouping of each group were almost equal by a random method using a computer. After grouping, the powdered feed was replaced with a standard diet (AIN-93G manufactured by Oriental Yeast Co., Ltd.) and reared in the same manner. The effect of adding cellooligosaccharide is to fix sucrose in the above-mentioned standard food, and 2.5 or 5% by mass of the components other than sucrose is added to each cellooligosaccharide powder of CE-1 to 3 shown in Table 1. Instead, comparison was made. Table 2 shows the results of 30-day breeding and 60-day breeding.
[比較例1、2]
セロオリゴ糖としてCE−3、CE−4を用いる以外は、実施例2と同じ条件で飼育を行った。結果を表2に示す。
[Comparative Examples 1 and 2]
Breeding was performed under the same conditions as in Example 2 except that CE-3 and CE-4 were used as cellooligosaccharides. The results are shown in Table 2.
[比較例3]
コントロールとして、セロオリゴ糖を添加せず、標準食単独で飼育を行った。結果を表2に示す。摂餌量および体重は、試験を通し、実施例と比較例で有意差はなかった。
[Comparative Example 3]
As a control, no cellooligosaccharide was added and the standard diet alone was raised. The results are shown in Table 2. Food intake and body weight were not significantly different between Examples and Comparative Examples throughout the study.
<飼料組成>
カゼイン 20.0質量%
L−システイン 0.3質量%
コーンスターチ 39.7質量%
α化コーンスターチ 13.2質量%
ショ糖 10.0質量%
大豆油 7.0質量%
セルロースパウダー 5.0質量%
AIN−93ミネラル混合 3.5質量%
AIN−93ビタミン混合 1.0質量%
重酒石酸コリン 0.25質量%
第三ブチルヒドロキノン 0.0014質量%
※セロオリゴ糖添加系は、上述のショ糖量10.0質量%を固定し、その他の成分を混合物として、飼料総量に対し、5.0質量%をおきかえた。
<Feed composition>
Casein 20.0 mass%
L-cysteine 0.3% by mass
Corn starch 39.7% by mass
Pregelatinized corn starch 13.2% by mass
Sucrose 10.0% by mass
Soybean oil 7.0% by mass
Cellulose powder 5.0% by mass
AIN-93 mineral mixture 3.5% by mass
AIN-93 vitamin mix 1.0% by mass
Choline bitartrate 0.25 mass%
Tertiary butyl hydroquinone 0.0014% by mass
* In the cellooligosaccharide addition system, the above-mentioned sucrose amount of 10.0% by mass was fixed, and the other components were mixed to replace 5.0% by mass with respect to the total amount of feed.
<試験項目および方法>
(体重測定)
群分け後30日、60日後において、各マウスの体重を測定した。
(摂餌量測定)
群分け後8、15、30、60日後に、各マウスのその日の摂餌量を測定した。
(採血および血液分析)
群分け後、15日、30日、60日後に、ヘパリン処理したキャピラリーを用いて、尾静脈から約100μLの血液を採血した。得られた血液は、遠心機(日立工機(株)製 商品名CF8DL)で、4℃、1972G、15分間の条件で遠心分離し、血漿について以下の項目の測定を行った。
・血中アディポネクチン濃度(大塚製薬製 アディポELISAキットを使用)
・血漿中性脂肪(和光純薬製 トリグリセライドE−テストワコーを使用)
・血漿総コレステロール(和光純薬製 コレステロール−E−テストワコーを使用)
(摘出器官についての測定)
投与60日後に、塩酸ケタミン50mg/kgおよびキシラジン2mg/kgの腹腔内投与麻酔下で、肝臓および副睾丸脂肪を摘出後、重量を測定し、液体窒素で凍結した。肝臓内の脂質は、上記の肝臓から脂質をヘキサン抽出し、肝臓内の総コレステロール濃度および中性脂肪濃度を測定した。
<Test items and methods>
(Weight measurement)
The body weight of each mouse was measured 30 days and 60 days after grouping.
(Feed consumption measurement)
After 8, 15, 30, and 60 days after grouping, the food intake of each mouse was measured on that day.
(Blood collection and blood analysis)
After the grouping, about 100 μL of blood was collected from the tail vein using heparinized capillaries on the 15th, 30th, and 60th days. The obtained blood was centrifuged with a centrifuge (trade name CF8DL, manufactured by Hitachi Koki Co., Ltd.) at 4 ° C., 1972 G, for 15 minutes, and the following items were measured for plasma.
・ Adiponectin concentration in blood (using Atsuka Pharmaceutical Adipo ELISA kit)
・ Plasma triglyceride (using Triglyceride E-Test Wako manufactured by Wako Pure Chemical Industries)
・ Plasma total cholesterol (Cholesterol-E-Test Wako manufactured by Wako Pure Chemical Industries, Ltd. is used)
(Measurement on isolated organs)
Sixty days after administration, the liver and epididymal fat were removed under intraperitoneal anesthesia with 50 mg / kg of ketamine hydrochloride and 2 mg / kg of xylazine, and then weighed and frozen in liquid nitrogen. Lipids in the liver were extracted from the liver with hexane and the total cholesterol concentration and neutral fat concentration in the liver were measured.
表2の結果より、いずれの実施例も同一飼育期間において、血中アディポネクチンの低下率は30%以下に抑制され、肝臓内の中性脂肪濃度低下率も15%以上であった。それに対し、比較例1、2は血中アディポネクチン低下率、肝臓の中性脂肪濃度低下率ともに、本発明の範囲になかった。
また、実施例1〜3のセロオリゴ糖添加系は、比較例3に対し、血漿、腹腔内脂質において有意な低下を示した。実施例1と実施例2とを比較すると、飼料中のセロオリゴ糖含量が増加すると、短期間で効果が発現し、長期投与では、絶対値が低下した。実施例2と3の比較により、セロトリオース〜セロヘキサオースの含量が高いと、血中の効果発現は遅いが、肝臓脂質の低下が促進された。
また、比較例1と、実施例1〜3を比べると、飼料中のグルコース含量が多くとも、副睾丸脂質の低下作用を有するが、血中脂質への効果発現が遅れ、肝臓脂質には有意差はみられなかった。
さらに、比較例2は、セロビオース含量が70質量%未満であり、本発明の範囲にないため、実施例および比較例1に対し、副睾丸脂質量、血中脂質への効果が小さくなった。
From the results shown in Table 2, the reduction rate of blood adiponectin was suppressed to 30% or less and the neutral fat concentration reduction rate in the liver was 15% or more in the same breeding period. On the other hand, Comparative Examples 1 and 2 had neither a blood adiponectin reduction rate nor a liver neutral fat concentration reduction rate within the scope of the present invention.
Moreover, the cellooligosaccharide addition system of Examples 1-3 showed the significant fall in plasma and an intraperitoneal lipid with respect to the comparative example 3. FIG. When Example 1 and Example 2 were compared, when the cellooligosaccharide content in the feed increased, the effect appeared in a short period, and the absolute value decreased in the long-term administration. According to the comparison between Examples 2 and 3, when the content of cellotriose to cellohexaose was high, the expression of effects in blood was slow, but the decrease in liver lipid was promoted.
In addition, when Comparative Example 1 and Examples 1 to 3 are compared, even if the glucose content in the feed is large, it has an effect of lowering the testicular lipids, but the effect on blood lipids is delayed, which is significant for liver lipids. There was no difference.
Furthermore, since the cellobiose content of Comparative Example 2 is less than 70% by mass and is not within the scope of the present invention, the effect on the amount of epididymis lipid and blood lipid was smaller than that of Example and Comparative Example 1.
<健常ラットにおける生活習慣病改善>
[実施例4、5]
実験動物として、5週齢の雄SDラット(日本クレア製)を用いた。ラットは、個別のステンレスケージに入れて、室温23±5℃、湿度40〜70%、明暗各12時間(照明午前7時〜午後7時)、換気12回/時(フィルターにより除菌した新鮮空気)に維持された飼育室で動物を飼育した。
まず、5日間の予備飼育を行い、予備飼育中は、粉末飼料(CRF−1 オリエンタル酵母工業製)を給餌器に入れ、自由摂取させた。また、飲水として水道水を用い、飼育期間中は自由摂取させた。
予備飼育の後、コンピューターを用いた無作為法により、各群の群分け前の血糖値、体重がほぼ等しくなるように、1群10匹構成で群分けを行った。群分け後も、粉末飼料代えることなく、同様に飼育した。
セロオリゴ糖は、上述のCE−1を精製水に溶解または懸濁し、160、1000mg/kgを、ゾンデを用いて、1回/日、13週間投与した。投与後、ペントバルビタール・ナトリウム30mg/kgを腹腔内に投与して麻酔した後、後大静脈腹部より血液を2.0〜2.5mL採血し、3.8w/v%クエン酸ナトリウム0.1mLを入れた試験管に血液0.9mLを分注し、1870Gで15分間遠心分離した。遠心後の血漿を用い、上述と同様に、血中アディポネクチン濃度、血漿および肝臓内の中性脂肪濃度を測定した。
<Improvement of lifestyle-related diseases in healthy rats>
[Examples 4 and 5]
As experimental animals, 5-week-old male SD rats (manufactured by CLEA Japan) were used. Rats are placed in individual stainless cages, room temperature 23 ± 5 ° C., humidity 40-70%, light and darkness 12 hours each (lighting 7 am to 7 pm), ventilation 12 times / hour (fresh sterilized by filter) Animals were raised in a breeding room maintained in air.
First, pre-breeding for 5 days was performed, and during the pre-breeding, powdered feed (CRF-1 Oriental Yeast Co., Ltd.) was placed in a feeder and allowed to freely take. In addition, tap water was used as drinking water and allowed to freely ingest during the breeding period.
After the preliminary breeding, the grouping was performed in a group of 10 animals so that the blood glucose level and the body weight before grouping of each group were almost equal by a random method using a computer. After grouping, the animals were reared in the same manner without changing the powdered feed.
The cellooligosaccharide was obtained by dissolving or suspending the above-mentioned CE-1 in purified water, and administering 160, 1000 mg / kg once / day for 13 weeks using a sonde. After administration, 30 mg / kg of pentobarbital sodium was intraperitoneally administered and anesthetized, and then 2.0 to 2.5 mL of blood was collected from the abdomen of the posterior vena cava, and 3.8 w / v% sodium citrate 0.1 mL 0.9 ml of blood was dispensed into the test tube containing the sample and centrifuged at 1870 G for 15 minutes. Using the plasma after centrifugation, the blood adiponectin concentration, the plasma and the neutral fat concentration in the liver were measured in the same manner as described above.
[比較例4]
セロオリゴ糖を投与しない以外は、実施例4と同様の操作で、飼育し、血中アディポネクチン濃度、血漿および肝臓内の中性脂肪濃度を測定した。
摂餌量および体重は、試験を通し、実施例と比較例で有意差はなかった。
[Comparative Example 4]
The animals were reared in the same manner as in Example 4 except that no cellooligosaccharide was administered, and the blood adiponectin concentration, plasma, and neutral fat concentration in the liver were measured.
Food intake and body weight were not significantly different between Examples and Comparative Examples throughout the study.
表3より、実施例は、比較例に対し、アディポネクチン濃度低下率が30%以下であり、肝臓内中性脂肪濃度の低下率が15%以上であり、本発明の範囲にあった。また、セロオリゴ糖投与系は、用量依存的に、血中および肝臓の脂質濃度が低下し、高用量系では肝臓重量も、低減する傾向がある。この試験により、健常ラットにおいても、セロオリゴ糖を摂取することで、摂餌量を変えずとも、血中および肝臓内脂質濃度を低減できた。 From Table 3, the Examples had a reduction rate of adiponectin concentration of 30% or less, and a reduction rate of neutral fat concentration in the liver of 15% or more, which was within the scope of the present invention. In the cellooligosaccharide administration system, blood and liver lipid concentrations decrease in a dose-dependent manner, and in a high-dose system, the liver weight tends to decrease. As a result of this test, in healthy rats, it was possible to reduce blood and hepatic lipid concentrations by ingesting cellooligosaccharide without changing food intake.
本発明のセロオリゴ糖を有効成分とする生活習慣病予防/改善剤は、肝蔵内脂質を低減できるため、一般食品、機能性食品、医薬品分野で好適に利用できる。 The lifestyle-related disease preventive / ameliorating agent containing the cellooligosaccharide of the present invention as an active ingredient can be suitably used in general foods, functional foods, and pharmaceutical fields because it can reduce hepatic lipids.
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JP2010226995A (en) * | 2009-03-26 | 2010-10-14 | Asahi Kasei Chemicals Corp | Frozen food and drink |
WO2016116627A1 (en) * | 2015-01-22 | 2016-07-28 | Pfeifer & Langen GmbH & Co. KG | Cellobiose in compositions for consumption or ingestion |
US10827765B2 (en) | 2015-06-19 | 2020-11-10 | Mars, Incorporated | Low calorie food compositions |
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JP2010226995A (en) * | 2009-03-26 | 2010-10-14 | Asahi Kasei Chemicals Corp | Frozen food and drink |
WO2016116627A1 (en) * | 2015-01-22 | 2016-07-28 | Pfeifer & Langen GmbH & Co. KG | Cellobiose in compositions for consumption or ingestion |
US10827765B2 (en) | 2015-06-19 | 2020-11-10 | Mars, Incorporated | Low calorie food compositions |
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