JP5186084B2 - Robofruit-containing saponin and its use - Google Patents
Robofruit-containing saponin and its use Download PDFInfo
- Publication number
- JP5186084B2 JP5186084B2 JP2006017928A JP2006017928A JP5186084B2 JP 5186084 B2 JP5186084 B2 JP 5186084B2 JP 2006017928 A JP2006017928 A JP 2006017928A JP 2006017928 A JP2006017928 A JP 2006017928A JP 5186084 B2 JP5186084 B2 JP 5186084B2
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- Prior art keywords
- saponin
- group
- extract
- compound
- robofruit
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Description
本発明は、ナス科(Solanaceae)植物であるロベイラ(Solanum lycocarpum)の果実；ロボフルーツが含有するサポニンを有効成分とする組成物に関する。
より具体的には、本発明は、有効成分としてロボフルーツ抽出物および該抽出物に含まれるサポニンの血糖値抑制効果、胃粘膜保護およびアレルギー抑制用組成物ならびにそれらの有効成分を含む健康食品に関する。
The present invention relates to a fruit composition of Solanum lycocarpum, a solanaceae plant; a composition comprising saponin contained in robofruit as an active ingredient.
More specifically, the present invention relates to a robofruit extract as an active ingredient, a blood glucose level inhibitory effect of saponin contained in the extract, a composition for protecting gastric mucosa and allergy, and a health food containing these active ingredients. .
我々は日常の食事において、主食あるいは副食として多くの炭水化物(例えばデンプンやショ糖など)を摂取している。摂取された炭水化物は、体内の酵素(例えばα-グルコシダーゼなど)により代謝され、単糖に分解された後、消化管から吸収される。 We eat a lot of carbohydrates (such as starch and sucrose) as a staple or side meal in our daily diet. Ingested carbohydrates are metabolized by enzymes in the body (such as α-glucosidase), decomposed into monosaccharides, and then absorbed from the digestive tract.
炭水化物の摂取量が増加すると、消化管から吸収され、血液中に移行する単糖の量も増加して高血糖となる。この高血糖が日常的に持続することにより、通常、肥満を経て糖尿病に罹患し、さらに場合によっては、糖尿病の悪化により合併症などの重大な疾病をもたらすことがある。 When the intake of carbohydrates increases, the amount of monosaccharides absorbed from the digestive tract and transferred into the blood also increases, resulting in hyperglycemia. The daily persistence of this hyperglycemia usually results in obesity and diabetes, and in some cases, worsening diabetes can lead to serious illnesses such as complications.
糖尿病による三大合併症として、通常、網膜症、神経障害および腎症があり、成人における失明の大部分が、糖尿病による網膜症に基づくと言われている。また、上記の三大合併症意外にも合併症として脳卒中や動脈硬化などの血管系疾患および高血圧症も知られている。 The three major complications due to diabetes are usually retinopathy, neuropathy and nephropathy, and it is said that the majority of blindness in adults is based on retinopathy due to diabetes. In addition to the above three major complications, vascular diseases such as stroke and arteriosclerosis and hypertension are also known as complications.
この糖尿病は、近年の食生活の欧米化、すなわち、高カロリー食の摂取および過食ならびに交通手段および交通機関の発達による生活習慣の変化、すなわち運動不足などが原因となり、成人のみならず若年にとっても増加する傾向にあり、現代病としてまた生活習慣病として大きな問題になっている。 Diabetes mellitus is caused not only by adults but also young people due to the recent westernization of eating habits, that is, intake and overeating of high-calorie diets and changes in lifestyle habits due to the development of transportation and transportation systems, such as lack of exercise. It tends to increase, becoming a major problem as a modern disease and a lifestyle-related disease.
現在、糖尿病の治療に用いられる医薬品としては、主に、膵インシュリン分泌促進作用を有するスルホニル尿素剤；肝の糖新生の抑制と末梢の筋肉、脂肪組織でのインシュリン感受性の亢進作用を有するビグアナイド系薬剤；消化管粘膜に存在し、デンプンやショ糖からブドウ糖を生成するα-グルコシターゼ(二糖類加水分解酵素)を阻害して血糖値上昇を抑制するα-グルコシダーゼ阻害剤(例えばアカルボースおよびボグリボース)等があり、経口投与用の糖尿病治療剤として広く使用されている。 Currently, the drugs used for the treatment of diabetes mainly include sulfonylureas that have a pancreatic insulin secretion-promoting effect; biguanides that inhibit liver gluconeogenesis and enhance insulin sensitivity in peripheral muscles and adipose tissue Drugs: α-glucosidase inhibitors (eg, acarbose and voglibose) that are present in the gastrointestinal mucosa and inhibit glucose-rise by inhibiting α-glucosidase (disaccharide hydrolase) that produces glucose from starch and sucrose And is widely used as a therapeutic agent for diabetes for oral administration.
しかしながら、上記の糖尿病治療剤は、一般に合成品であり、近年、胃腸障害、乳酸アシドーシスまたは重篤な肝障害の発生などが報告されており、その使用にあたっては医師の厳格な指導・管理が必要である。一方で、これらの副作用低減を目的とするアルドース還元酵素阻害剤(例えばエパルタット)等も広く使用されている。 However, the above-mentioned therapeutic agents for diabetes are generally synthetic products, and gastrointestinal disorders, lactic acidosis, or severe liver disorders have been reported in recent years, and strict guidance and management by doctors is necessary for their use. It is. On the other hand, aldose reductase inhibitors (for example, epartat) for the purpose of reducing these side effects are also widely used.
そこで、最近、副作用が少ない天然素材が注目され、健康食品としても種々上市されており、そのなかに抗糖尿病効果を標榜したものも多数認められるが、有効性に疑問のあるものが多く、具体的に効果が証明されたものがほとんどないのが実情である。 Therefore, recently, natural materials with few side effects have been attracting attention, and various foods have been put on the market as health foods. In fact, there are few things that have been proven effective.
ロベイラはナス科植物であり、ブラジルのセラード地帯やサンパウロ州に分布しており、従来、その果実は小鳥、げっ歯類、その他の小型または中型哺乳類の食用源となっている。
該果実は、ブラジルに生息しているロボ狼が好んで食していることからロボフルーツと称されているが、一方で、ブラジルの糖尿病、肥満およびコレステロール値の低下用民間薬としても使用されてきた。
Robeira is a solanaceous plant that is distributed in the Brazilian Cerrado and Sao Paulo provinces, and its fruit has traditionally been an edible source for small birds, rodents, and other small or medium-sized mammals.
The fruit is called Robofruit because it is favored by Robowolf living in Brazil, but it has also been used as a folk medicine for reducing diabetes, obesity and cholesterol levels in Brazil. It was.
上記の作用に関するロボフルーツの活性成分は、ペクチン、ロボフルーツの粘液質およびデンプンを含む多糖であることが報告されている(非特許文献１)。
また、一方で近年、ロボフルーツから抽出したアルカロイド画分が抗炎症作用を有することも報告されている(非特許文献２)。
It has been reported that the active ingredient of Robofruit related to the above action is a polysaccharide containing pectin, Robofruit mucus and starch (Non-patent Document 1).
On the other hand, it has recently been reported that the alkaloid fraction extracted from Robofruit has an anti-inflammatory action (Non-patent Document 2).
したがって、本発明は、ロボフルーツ抽出物が含む有効成分の特定および該抽出物に含まれる成分の新規用途の開発を課題とする。 Therefore, this invention makes it a subject to identify the active ingredient which Robofruit extract contains, and development of the novel use of the ingredient contained in this extract.
本発明者は、ナス科植物ロベイラの乾燥した果実、乾燥ロボフルーツの水または含水低級アルコール抽出物に含まれる生理活性物質について鋭意研究を行った結果、新規物質を含むサポニンが含有されることを見出した。さらに、本発明者は、該サポニン含有抽出物、該サポニン含有精製画分および該サポニンが、意外にも、血糖値上昇抑制、胃粘膜保護および抗アレルギー作用を有することを見出し、本発明を完成するに至った。 As a result of earnest research on the physiologically active substance contained in the dried fruit of the solanaceous plant Robeira, the water of the dried Robofruit or the water-containing lower alcohol extract, it has been found that the saponin containing the novel substance is contained. I found it. Furthermore, the present inventor has found that the saponin-containing extract, the saponin-containing purified fraction, and the saponin unexpectedly have an increase in blood glucose level, gastric mucosa protection, and an antiallergic action, thereby completing the present invention. It came to do.
すなわち、本発明によれば、ロボフルーツを水または含水低級アルコールで抽出したサポニン含有抽出物もしくはその濃縮物または該サポニン含有精製画分を有効成分として含む医薬組成物が提供される。
より具体的には、本発明によれば、ロボフルーツが含有する、一般式(Ｉ)：
That is, according to the present invention, there is provided a pharmaceutical composition comprising, as an active ingredient, a saponin-containing extract obtained by extracting robofruit with water or a hydrous lower alcohol, or a concentrate thereof, or a purified fraction containing saponin.
More specifically, according to the present invention, the general formula (I) contained in the robofruit:
で表されるサポニンを有効成分として含む医薬組成物が提供される。
The pharmaceutical composition which contains saponin represented by this as an active ingredient is provided.
さらに、より具体的には、本発明によれば、一般式(ＩＩ)：
で表される新規サポニンが提供される。
More specifically, according to the present invention, the general formula (II):
A new saponin represented by is provided.
また、上記医薬組成物は、血糖値上昇抑制、胃粘膜保護および抗アレルギー作用を有することが判明したので、これらの作用を意図する医薬組成物ならびに該組成物が添加されてなる健康食品が提供される。 Further, since the pharmaceutical composition has been found to have an increase in blood glucose level, gastric mucosa protection and antiallergic action, a pharmaceutical composition intended for these actions and a health food to which the composition is added are provided. Is done.
本発明によれば、ロボフルーツを水または含水低級アルコールで抽出したサポニン含有抽出物もしくはその濃縮物または該サポニン含有精製画分を有効成分として含み、安全に使用できる医薬組成物が提供される。また、該組成物が血糖値上昇抑制、胃粘膜保護またはアレルギー抑制に用いられる健康食品が提供される。 ADVANTAGE OF THE INVENTION According to this invention, the pharmaceutical composition which contains the saponin containing extract or its concentrate which extracted robofruit with water or water-containing lower alcohol, or this saponin containing purified fraction as an active ingredient can be used safely. In addition, a health food is provided in which the composition is used for suppressing an increase in blood glucose level, protecting gastric mucosa, or suppressing allergy.
本発明による、血糖値上昇抑制、胃粘膜保護またはアレルギー抑制に用いることができる医薬組成物は、ロボフルーツに含有されるサポニンを有効成分として含むことを特徴とする。
本発明による医薬組成物は、乾燥ロボフルーツを水または含水低級アルコールで抽出したサポニン含有抽出物もしくはその濃縮物、またはこの濃縮物をカラムクロマトグラフィーやＨＰＬＣのような各種従来技術を組合せて精製した該サポニン含有精製画分、あるいは単離した１以上のサポニンを有効成分として含むことができる。
したがって、本発明におけるサポニン含有精製画分とは、１以上のサポニンを含む精製画分も意味する。
The pharmaceutical composition according to the present invention, which can be used for suppressing blood sugar level elevation, gastric mucosa protection or allergy suppression, is characterized by containing saponin contained in Robofruit as an active ingredient.
The pharmaceutical composition according to the present invention is a saponin-containing extract obtained by extracting dried robofruit with water or a hydrous lower alcohol, or a concentrate thereof, or the concentrate is purified by combining various conventional techniques such as column chromatography and HPLC. The saponin-containing purified fraction or one or more isolated saponins can be included as an active ingredient.
Therefore, the saponin-containing purified fraction in the present invention also means a purified fraction containing one or more saponins.
本発明で抽出溶媒として用いられる含水低級アルコールとしては、炭素数１〜４のアルコール類が挙げられ、具体的には、メタノール、エタノール、プロパノール、イソプロパノール、n-ブタノール、イソブタノール、t-ブタノールもしくはこれらの混液またはこれらの５０容量％程度までの水を含有する水性アルコール等が挙げられるが、特に低級アルコールの含水率は限定されるものではない。なかでも、メタノールまたはエタノールが特に好ましい。
これらの抽出溶媒は、抽出材料に対して、１〜５０倍(容量)程度、好ましくは２〜１０倍(容量)程度用いられる。
Examples of the hydrous lower alcohol used as the extraction solvent in the present invention include alcohols having 1 to 4 carbon atoms, specifically, methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, t-butanol or These mixed liquids or aqueous alcohols containing up to about 50% by volume of water may be mentioned, but the water content of the lower alcohol is not particularly limited. Of these, methanol or ethanol is particularly preferable.
These extraction solvents are used in an amount of about 1 to 50 times (volume), preferably about 2 to 10 times (volume) with respect to the extraction material.
なお、抽出は、熱時または室温で行うことができ、抽出温度は、室温と溶媒の沸点の間で任意に設定できる。熱時抽出の場合、例えば、50℃〜抽出溶媒の沸点の温度で、振盪もしくは撹拌下または非振盪下もしくは還流下に、ブラジル産の粉砕または破砕した乾燥ロボフルーツを上記の抽出溶媒に浸漬することによって行うのが適当である。
抽出材料を振盪下に浸漬する場合には、30分間〜5時間程度行うのが適当であり、非振盪下に浸漬する場合には、1時間〜20日間程度行うのが適当である。
また、抽出溶媒の還流下に抽出する場合には、３０分〜数時間加熱還流するのが好ましい。
The extraction can be performed while heating or at room temperature, and the extraction temperature can be arbitrarily set between room temperature and the boiling point of the solvent. In the case of hot extraction, for example, Brazilian ground or crushed dried robofruit is immersed in the extraction solvent at a temperature between 50 ° C. and the boiling point of the extraction solvent, with shaking or stirring, or without shaking or refluxing. It is appropriate to do so.
When the extraction material is immersed under shaking, it is appropriate to perform for about 30 minutes to 5 hours, and when it is immersed under non-shaking, it is appropriate for about 1 hour to 20 days.
Moreover, when extracting under reflux of an extraction solvent, it is preferable to heat to reflux for 30 minutes to several hours.
さらに、５０℃より低い温度で浸漬して抽出することも可能であるが、その場合には、上記の時間よりも長時間浸漬するのが好ましい。抽出操作は、同一材料について1回だけ行ってもよいが、複数回、例えば、2〜5回程度繰り返すのが抽出効率の点から好ましい。 Furthermore, it is possible to extract by dipping at a temperature lower than 50 ° C. In this case, it is preferable to soak for a longer time than the above time. The extraction operation may be performed only once for the same material, but it is preferable from the viewpoint of extraction efficiency to repeat a plurality of times, for example, about 2 to 5 times.
抽出後に、固形物をろ別して得られる抽出物は、常法により濃縮して濃縮物(抽出エキス)としてもよい。濃縮は、減圧下に行うのが好ましい。濃縮は抽出液が乾固するまで行ってもよい。
抽出物は、そのまま本発明の組成物を調製するのに用いてもよいが、粉末状または凍結乾燥品等として用いてもよい。これらの固形物とする方法は、当該分野で公知の方法を採用することができる。
After the extraction, the extract obtained by filtering the solid may be concentrated by a conventional method to obtain a concentrate (extract extract). Concentration is preferably performed under reduced pressure. Concentration may be performed until the extract is dry.
The extract may be used as it is to prepare the composition of the present invention, but may also be used as a powder or lyophilized product. A method known in the art can be adopted as the method for forming these solids.
したがって、本発明における抽出物とは抽出液を意味し、濃縮物とは該抽出液を濃縮した抽出エキス、濃縮乾固物または凍結乾燥物のいずれも意味する。 Therefore, the extract in the present invention means an extract, and the concentrate means any of an extract, a concentrated dry solid or a freeze-dried product obtained by concentrating the extract.
なお、上記の水または含水低級アルコール抽出物およびその濃縮物は、濃縮する前後に精製処理に付すことができる。
精製処理には、当業者に公知のクロマトグラフ法、イオン交換クロマトグラフ法等を単独で、または組み合わせて採用することができる。例えば、クロマトグラフ法としては、順相もしくは逆相担体またはイオン交換樹脂を用いるカラムクロマトグラフィー、薄層クロマトグラフィー、高速液体クロマトグラフィーまたは遠心液体クロマトグラフィー等のいずれか、またはそれらを組み合わせて行う方法が挙げられる。この際の担体、溶出溶媒等の精製条件は、各種クロマトグラフィーおよび使用する担体に対応して適宜選択することができる。
The water or water-containing lower alcohol extract and the concentrate thereof can be subjected to a purification treatment before and after concentration.
For the purification treatment, chromatographic methods, ion-exchange chromatographic methods and the like known to those skilled in the art can be used alone or in combination. For example, as a chromatographic method, a column chromatography, a thin layer chromatography, a high performance liquid chromatography, a centrifugal liquid chromatography or the like using a normal phase or reverse phase carrier or an ion exchange resin, or a combination thereof is performed. Is mentioned. In this case, the purification conditions such as the carrier and the elution solvent can be appropriately selected according to various chromatography and the carrier to be used.
本発明者は、ロボフルーツの水または含水低級アルコール抽出物を上記の精製方法を組み合わせて精製し、該アルコール可溶性抽出物の含有成分について検討した。
したがって、本願発明における精製画分とは、抽出エキスを上記の精製方法を単独でまたは組合せて、本発明によるサポニン含有抽出物またはその濃縮物を分離精製し、単離したサポニンもしくはサポニンの混合物またはこれらを含むクロマトグラフィーの溶出画分あるいはその濃縮物のいずれも意味するが、本発明によるサポニン含有抽出物は、精製せずにそのまま用いることもでき、本発明の一部を構成している。
This inventor refine | purified the water or water-containing lower alcohol extract of Robofruit combining the said refinement | purification method, and examined the content component of this alcohol soluble extract.
Therefore, the purified fraction in the present invention refers to an isolated saponin or a mixture of saponins obtained by separating and purifying the saponin-containing extract or the concentrate thereof according to the present invention by combining the above-mentioned purification methods alone or in combination with the extract. It means any chromatographic elution fraction containing these or a concentrate thereof, but the saponin-containing extract according to the present invention can be used as it is without purification and constitutes a part of the present invention.
本発明者は、乾燥ロボフルーツを水または含水低級アルコールで抽出して抽出物を得、この抽出物を減圧下に濃縮して、濃縮物を得た。 The present inventor extracted a dried robofruit with water or water-containing lower alcohol to obtain an extract, and the extract was concentrated under reduced pressure to obtain a concentrate.
ここに得られた濃縮物を、ダイヤイオン(登録商標)ＨＰ-２０を担体とするクロマトグラフィー、シリカゲルクロマトグラフィー、逆相シリカクロマトグラフィーおよび/またはＯＤＳカラムを用いたHPLCによる精製を組合せ、含有成分の単離を行った。 The concentrate obtained here was combined with chromatography using Diaion (registered trademark) HP-20 as a carrier, silica gel chromatography, reverse phase silica chromatography and / or purification by HPLC using an ODS column, Was isolated.
その結果、本発明者は、既知サポニン化合物としてソルマルジン(化合物(III))、ソラソニン(化合物(IV))および１２-ヒドロキシソラソニン(化合物(VII))を得た。
本発明者は、さらに、ソルマルジンの１２-α-ヒドロキシ体(化合物(V))およびソラソニンの１２-α-ヒドロキシ体(化合物(VI))を新規サポニン化合物として見出した。
As a result, the present inventors obtained solmardin (compound (III)), solasonine (compound (IV)) and 12-hydroxysolasonine (compound (VII)) as known saponin compounds.
The present inventor has further found 12-α-hydroxy form of solmardin (compound (V)) and 12-α-hydroxy form of solasonine (compound (VI)) as novel saponin compounds.
すなわち、本発明によれば、次の、一般式(Ｉ)：
で表されるサポニンを有効成分とする医薬組成物が提供される。
That is, according to the present invention, the following general formula (I):
The pharmaceutical composition which uses saponin represented by these as an active ingredient is provided.
より具体的には、本発明は、式(III)：
すなわち、本発明者は、上記の化合物(III)〜(VII)の少なくとも一つおよび/または上記の化合物の含有画分が、いずれも血糖値上昇抑制に対して強い活性を有することを見出し、本発明を完成した。
したがって、本発明によれば、ロボフルーツに含まれるサポニンの少なくとも一つを有効成分として含む血糖値上昇抑制用組成物が提供される。
That is, the present inventor has found that at least one of the above compounds (III) to (VII) and / or a fraction containing the above compound has a strong activity for suppressing an increase in blood glucose level, The present invention has been completed.
Therefore, according to the present invention, there is provided a composition for suppressing an increase in blood glucose level comprising at least one saponin contained in robofruit as an active ingredient.
また、本発明者は、上記の化合物(III)〜(VII)の少なくとも一つおよび/または上記の化合物の含有画分が、いずれも胃粘膜保護に対して強い活性を有することを見出し、本発明を完成した。
したがって、本発明によれば、ロボフルーツに含まれるサポニンの少なくとも一つを有効成分として含む胃粘膜保護用組成物が提供される。
Further, the present inventor has found that at least one of the above compounds (III) to (VII) and / or a fraction containing the above compound has a strong activity for protecting the gastric mucosa. Completed the invention.
Therefore, according to the present invention, there is provided a composition for protecting gastric mucosa comprising at least one saponin contained in robofruit as an active ingredient.
さらに、本発明者は、上記の化合物(III)〜(VII)の少なくとも一つおよび/または上記の化合物の含有画分が、いずれもアレルギー抑制に対して強い活性を有することを見出し、本発明を完成した。
したがって、本発明によれば、ロボフルーツに含まれるサポニンの少なくとも一つを有効成分として含むアレルギー抑制用組成物が提供される。
すなわち、本発明によれば、現代病として代表的な糖尿病、胃障害およびアレルギーなどの予防または治療を意図した医薬組成物が提供される。
その上、本発明によれば、該組成物を含む健康食品が提供される。
Furthermore, the present inventor has found that at least one of the above-mentioned compounds (III) to (VII) and / or a fraction containing the above-mentioned compound all have a strong activity against allergy suppression, and the present invention Was completed.
Therefore, according to this invention, the composition for allergy suppression which contains at least one of the saponins contained in a robofruit as an active ingredient is provided.
That is, according to the present invention, there is provided a pharmaceutical composition intended for the prevention or treatment of diabetes, stomach disorders and allergies that are typical of modern diseases.
Moreover, according to the present invention, a health food containing the composition is provided.
本発明のロボフルーツを水または含水低級アルコールで抽出したサポニン含有抽出物、その濃縮物または該サポニン含有精製画分は、そのままの状態、または適当な媒体で希釈して、あるいは医薬品の製造分野において公知の方法により、散剤、顆粒剤、錠剤、カプセル剤または液剤等、種々の医薬品の形態に製剤化して使用することができる。 The saponin-containing extract obtained by extracting the robofruit of the present invention with water or a hydrous lower alcohol, the concentrate thereof or the purified fraction containing the saponin is diluted as it is or with an appropriate medium, or in the pharmaceutical production field. It can be formulated into various pharmaceutical forms such as powders, granules, tablets, capsules or liquids by known methods.
これらの医薬品形態においては、適当な媒体を添加してもよい。そのような媒体としては、医薬的に許容される賦形剤、例えば結合剤(例えばシロップ、アラビアゴム、ゼラチン、ソルビトール、トラガントまたはポリビニルピロリドン)、充填剤(例えば乳糖、砂糖、トウモロコシ澱粉、リン酸カルシウム、ソルビトールまたはグリシン)、滑沢剤(例えばステアリン酸マグネシウム、タルクまたはポリエチレングリコール)、崩壊剤(例えば馬鈴薯澱粉)または湿潤剤(例えばラウリル硫酸ナトリウム)等が挙げられる。 In these pharmaceutical forms, an appropriate medium may be added. Such vehicles include pharmaceutically acceptable excipients such as binders (e.g. syrup, gum arabic, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone), fillers (e.g. lactose, sugar, corn starch, calcium phosphate, Sorbitol or glycine), lubricants (eg magnesium stearate, talc or polyethylene glycol), disintegrants (eg potato starch) or wetting agents (eg sodium lauryl sulfate).
錠剤は、通常の方法でコーティングしてもよい。液体製剤は、例えば水性または油性の懸濁液、溶液、エマルジョン、シロップまたはエリキシルの形態であってもよく、使用前に水または他の適切な賦形剤で再生する乾燥製品として提供してもよい。 Tablets may be coated by conventional methods. Liquid formulations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, and may be provided as a dry product that is regenerated with water or other suitable excipients prior to use. Good.
こうした液体製剤は、通常の添加剤、例えば懸濁化剤(例えばソルビトール、シロップ、メチルセルロース、グルコースシロップ、ゼラチン水添加食用脂)、乳化剤(例えばレシチン、ソルビタンモノオレエートまたはアラビアゴム)、(食用脂を含んでいてもよい)非水性賦形剤(例えばアーモンド油、分画ココヤシ油またはグリセリン、プロピレングリコールまたはエチルアルコールのような油性エステル)、保存剤(例えばｐ-ヒドロキシ安息香酸メチルまたはプロピル、またはソルビン酸)、および所望により着色剤または香料等を含んでいてもよい。 Such liquid preparations are made up of conventional additives such as suspending agents (e.g. sorbitol, syrup, methylcellulose, glucose syrup, gelatin edible fats), emulsifiers (e.g. lecithin, sorbitan monooleate or gum arabic), (edible fats). Non-aqueous excipients (e.g. almond oil, fractionated coconut oil or oily esters such as glycerin, propylene glycol or ethyl alcohol), preservatives (e.g. methyl or propyl p-hydroxybenzoate, or Sorbic acid) and, if desired, colorants or fragrances.
また、本発明による組成物を有効成分として食品に添加したものを健康食品として利用することができる。 Moreover, what added the composition by this invention to food as an active ingredient can be utilized as health food.
健康食品とは、通常の食品よりも積極的な意味で保健、健康維持・増進等を目的とした食品を意味し、例えば、固形、半固形または液体の製品、具体的には、散剤、顆粒剤、錠剤、カプセル剤または液剤等のほか、クッキー、せんべい、ゼリー、ようかん、ヨーグルト、まんじゅう等の菓子類、清涼飲料、お茶類、栄養飲料、スープ等の形態が挙げられる。
これらの食品の製造工程において、あるいは最終製品に、上記の抽出物を添加して、健康食品とすることができる。
Health food means food with a more positive meaning than normal food for the purpose of health, health maintenance and promotion, for example, solid, semi-solid or liquid products, specifically powders, granules In addition to pills, tablets, capsules or liquids, confectionery such as cookies, rice crackers, jelly, yokan, yogurt and manju, soft drinks, teas, nutritional drinks, soups and the like can be mentioned.
In the production process of these foods or to the final product, the above-mentioned extract can be added to make a health food.
本発明による、ロボフルーツを水または含水低級アルコールで抽出したサポニン含有抽出物もしくはその濃縮物または該サポニン含有精製画分を有効成分として含む医薬組成物の使用量は、年齢、症状等によって異なるが、例えば該抽出物の濃縮乾固物を予防・治療に用いる場合には、成人１回につき0.1〜10ｇ程度、好ましくは0.3〜2ｇ程度使用できる。また、健康食品として使用する場合には、食品の味や外観に悪影響を及ぼさない量、例えば、対象となる食品１ｋｇに対し上記乾固物を、0.1〜10ｇ程度の範囲で用いることができる。 The amount of the saponin-containing extract obtained by extracting the robofruit with water or water-containing lower alcohol, or a concentrate thereof, or a pharmaceutical composition containing the purified fraction containing saponin as an active ingredient according to the present invention varies depending on age, symptoms, etc. For example, when using the concentrated dried product of the extract for prevention / treatment, about 0.1 to 10 g, preferably about 0.3 to 2 g can be used per adult. Moreover, when using as a health food, the said dry-solid thing can be used in the quantity which does not have a bad influence on the taste and external appearance of a foodstuff, for example, the said dried solid substance with respect to 1 kg of target foodstuffs in the range of about 0.1-10 g.
以下、本発明のロボフルーツの抽出物、化合物(III)〜(VII)の精製法およびそれらの作用に関する実施例を具体的に説明するが、以下の実施例は、本発明を説明するためのものであり、本発明を何等制限するものではない。 Examples of the robofruit extract of the present invention, the purification methods of compounds (III) to (VII) and their actions will be specifically described below, but the following examples are for explaining the present invention. However, the present invention is not limited in any way.
なお、実施例では、特に記載がない限り、以下の各種溶媒、クロマトグラフィー用担体およびHPLC用カラムを用いた：
Wistar系雄性ラット：紀和実験動物研究所(和歌山)
Sprague-Dowley系雄性ラット：紀和実験動物研究所(和歌山)
ddYマウス：紀和実験動物研究所(和歌山)
メタノール(MeOH)：ナカライテスク社製、特級
エタノール(EtOH)：ナカライテスク社製、特級
クロロホルム：ナカライテスク社製、特級
抗ＤＮＰ ＩｇＥ抗体：シグマ社Clone SPE-7
ジニトロフェニル化牛血清アルブミン：T. Tadaら、J. Immunol、106、第1002〜1011頁(1971)に記載の方法に従って調製した。
In the examples, unless otherwise specified, the following various solvents, chromatographic carriers and HPLC columns were used:
Wistar male rats: Kiwa Laboratory Animal Research Institute (Wakayama)
Sprague-Dowley male rat: Kiwa Laboratory Animal Research Institute (Wakayama)
ddY mouse: Kiwa Laboratory Animal Research Institute (Wakayama)
Methanol (MeOH): Nacalai Tesque, special grade Ethanol (EtOH): Nacalai Tesque, special grade Chloroform: Nacalai Tesque, special grade Anti-DNP IgE antibody: Sigma Clone SPE-7
Dinitrophenylated bovine serum albumin: prepared according to the method described in T. Tada et al., J. Immunol, 106, pp. 1002-1011 (1971).
カラムクロマトグラフィー用シリカゲル (SiO2)：富士シリシア社製、ＢＷ-200、150〜350メッシュ
カラムクロマトグラフィー用ODSシリカゲル：富士シリシア社製、Chromatorex ODS DM1020T、100〜200メッシュ。
HPLC用ODSカラム：YMC社製、YMC-Pack ODS-A (250×20mm)
核磁気共鳴(ＮＭＲ)スペクトル測定装置：ＪＥＯＬ（JNM-LA 500）
Silica gel for column chromatography (SiO 2 ): Fuji Silysia, BW-200, 150 to 350 mesh ODS silica gel for column chromatography: Fuji Silysia, Chromatorex ODS DM1020T, 100 to 200 mesh.
ODS column for HPLC: YMC, YMC-Pack ODS-A (250 × 20mm)
Nuclear magnetic resonance (NMR) spectrometer: JEOL (JNM-LA 500)
また、核磁気共鳴(NMR)スペクトルにおいて、化学シフトδは百万分の一 (ppm)で表示し、略語はそれぞれ次の意味を有する：s：シングレット； d：ダブレット；dd：ダブルダブレット；t：トリプレット； q：クァルテット；dq：ダブルクァルテット；Ac；アセチル基；Glc：グルコピラノシル基；Rha：ラムノピラノシル基。 In nuclear magnetic resonance (NMR) spectra, chemical shift δ is expressed in parts per million (ppm), and abbreviations have the following meanings: s: singlet; d: doublet; dd: double doublet; : Triplet; q: quartet; dq: double quartet; Ac; acetyl group; Glc: glucopyranosyl group; Rha: rhamnopyranosyl group.
実施例１
乾燥ロボフルーツ抽出物の調製および該抽出物の精製
例えば、メタノールを用いて、乾燥ロボフルーツ抽出物を調製し、該抽出物を精製した例を表１に示し、以下の手順で行った。
Example 1
Preparation of dried robofruit extract and purification of the extract For example, a dry robofruit extract was prepared using methanol and the extract was purified. Table 1 shows an example in which the extract was purified, and the procedure was as follows.
得られたMeOH溶出部のうち70.0 gを、順相カラムクロマトグラフィー[シリカゲル；2.1 kg、溶出溶媒；CHCl3 ： MeOH：H2O = (40：10：1) → (30：10：1) → (6：4：1) → MeOH]で精製して、フラクション(Fr.) 1 (2.0 g)、Fr. 2 (1.8 g)、Fr. 3 (2.2 g)、Fr. 4 (1.0 g)、Fr. 5 (0.2 g)、Fr. 6 (1.6 g)、Fr. 7 (1.6g)、Fr. 8 (13.0g)、Fr. 9 (18.0 g)、Fr. 10 (28.0 g)およびFr. 11 (2.0 g)の各画分を得た。Fr. 1、Fr. 2 (3.8 g)を、逆相カラムクロマトグラフィー[ODS；100 g、溶出溶媒；MeOH：H2O = (50：50) → (70：30) → (90：10) → MeOH]で精製して、Fr.1-1 (300mg)、Fr.1-2 (500mg)、Fr.1-3 (720mg)、Fr.1-4 (γ-リノレン酸；500mg、0.022%)、Fr.1-5 (1.04 g)、Fr.1-6 (リノール酸；500mg、0.022%) およびFr.1-7 (220 mg)の各画分を得た。 70.0 g of the obtained MeOH elution part was subjected to normal phase column chromatography [silica gel; 2.1 kg, elution solvent; CHCl 3 : MeOH: H 2 O = (40: 10: 1) → (30: 10: 1) → (6: 4: 1) → MeOH], fractions (Fr.) 1 (2.0 g), Fr. 2 (1.8 g), Fr. 3 (2.2 g), Fr. 4 (1.0 g) , Fr. 5 (0.2 g), Fr. 6 (1.6 g), Fr. 7 (1.6 g), Fr. 8 (13.0 g), Fr. 9 (18.0 g), Fr. 10 (28.0 g) and Fr Each fraction of 11 (2.0 g) was obtained. Fr. 1, Fr. 2 (3.8 g) was subjected to reverse phase column chromatography [ODS; 100 g, elution solvent; MeOH: H 2 O = (50:50) → (70:30) → (90:10) → MeOH], Fr.1-1 (300 mg), Fr.1-2 (500 mg), Fr.1-3 (720 mg), Fr.1-4 (γ-linolenic acid; 500 mg, 0.022% ), Fr.1-5 (1.04 g), Fr.1-6 (linoleic acid; 500 mg, 0.022%) and Fr.1-7 (220 mg) were obtained.
次いで、Fr. 8 (2.0g)を逆相カラムクロマトグラフィー[ODS；60 g、溶出溶媒；MeOH：H2O = (50：50) → MeOH]で精製して、Fr.8-1 (0.98g)、Fr.8-2 (化合物(III)；1.02g、0.308%)の各画分を得た。 Fr. 8 (2.0 g) was then purified by reverse phase column chromatography [ODS; 60 g, elution solvent; MeOH: H 2 O = (50:50) → MeOH] to obtain Fr. 8-1 (0.98 g) and Fr.8-2 (compound (III); 1.02 g, 0.308%) were obtained.
また、Fr. 9(2.0g)を逆相カラムクロマトグラフィー[ODS；60 g、溶出溶媒；MeOH：H2O = (30：70) → (50：50) → (70：30) → MeOH]で精製して、Fr.9-1 (980mg)、Fr.9-2 (60mg)、Fr.9-3 (10mg)、Fr.9-4 (化合物(IV)；550mg、0.218%)、Fr.9-5 (30mg)、Fr.9-6 (化合物(III)；330mg、0.130%)およびFr.9-7 (20 mg)の各画分を得た。さらに、Fr9-5 (30mg)をHPLC [カラム：YMC-Pack ODS-A、移動層；MeOH：H2O = (60：40)、流速：9.0 ml/分]で精製して、化合物(IV) (5 mg、0.0019 %)および新規化合物(V) (5 mg、0.0019 %)を単離した。 In addition, Fr. 9 (2.0 g) was subjected to reverse phase column chromatography [ODS; 60 g, elution solvent; MeOH: H 2 O = (30:70) → (50:50) → (70:30) → MeOH] Fr.9-1 (980 mg), Fr.9-2 (60 mg), Fr.9-3 (10 mg), Fr.9-4 (compound (IV); 550 mg, 0.218%), Fr. .9-5 (30 mg), Fr.9-6 (compound (III); 330 mg, 0.130%) and Fr.9-7 (20 mg) were obtained. Further, Fr9-5 (30 mg) was purified by HPLC [column: YMC-Pack ODS-A, moving bed; MeOH: H 2 O = (60:40), flow rate: 9.0 ml / min] to obtain compound (IV ) (5 mg, 0.0019%) and the new compound (V) (5 mg, 0.0019%) were isolated.
さらに、Fr. 10(3.0g)を逆相カラムクロマトグラフィー[ODS；60 g、溶出溶媒；MeOH：H2O = (30：70) → (60：40) → MeOH]に付し、Fr.10-1 (1520mg)、Fr.9-2 (220mg)、Fr.10-3 (200mg)、Fr.10-4 (化合物(IV)；980mg、0.402%)の各画分を得た。ここで得られたFr10-3 (200mg)をHPLC [カラム：YMC-Pack ODS-A、移動層；MeOH：H2O = (60：40)、流速：9.0 ml/分]を用いて分離精製し、化合物(IV) (91 mg、0.037 %)および新規化合物(V) (15 mg、0.006 %)を単離した。 Furthermore, Fr. 10 (3.0 g) was subjected to reverse phase column chromatography [ODS; 60 g, elution solvent; MeOH: H 2 O = (30:70) → (60:40) → MeOH], and Fr. Fractions 10-1 (1520 mg), Fr.9-2 (220 mg), Fr.10-3 (200 mg), Fr.10-4 (compound (IV); 980 mg, 0.402%) were obtained. Fr10-3 (200 mg) obtained here was separated and purified using HPLC [column: YMC-Pack ODS-A, moving bed; MeOH: H 2 O = (60:40), flow rate: 9.0 ml / min]. Compound (IV) (91 mg, 0.037%) and novel compound (V) (15 mg, 0.006%) were isolated.
次いで、Fr. 11(2.0g)を逆相カラムクロマトグラフィー[ODS 60 g、溶出溶媒；MeOH：H2O = (10：90) → (30：70) → (50：50) → MeOH]に付し、Fr.11-1 (1100mg)、Fr.11-2 (220mg)、Fr.11-3 (100mg)、Fr.11-4 (130mg)、Fr11-5 (化合物(IV)；300mg、0.0133%)、Fr11-6 (160mg)の各画分を得た。さらに、Fr11-4 (130mg) をHPLC [カラム：YMC-Pack ODS-A、溶出溶媒；MeOH：H2O = (30：70)、流速：9.0ml/分]を用いて分離精製し、化合物(VII) (20 mg、0.00098 %)および新規化合物(VI) (12 mg、0.00062 %)を単離した。 Next, Fr. 11 (2.0 g) was subjected to reverse phase column chromatography [ODS 60 g, elution solvent; MeOH: H 2 O = (10:90) → (30:70) → (50:50) → MeOH] Fr.11-1 (1100 mg), Fr.11-2 (220 mg), Fr.11-3 (100 mg), Fr.11-4 (130 mg), Fr11-5 (compound (IV); 300 mg, 0.0133%) and Fr11-6 (160 mg) were obtained. Further, Fr11-4 (130 mg) was separated and purified using HPLC [column: YMC-Pack ODS-A, elution solvent; MeOH: H 2 O = (30:70), flow rate: 9.0 ml / min], and compound (VII) (20 mg, 0.00098%) and novel compound (VI) (12 mg, 0.00062%) were isolated.
既知化合物であるリノール酸、γ-リノレン酸、化合物(III)、化合物(IV)および化合物(VII)については、文献値との1H-NMR及び13C-NMRスペクトルデータの比較により同定した。 Known compounds such as linoleic acid, γ-linolenic acid, compound (III), compound (IV) and compound (VII) were identified by comparing 1 H-NMR and 13 C-NMR spectral data with literature values.
また、前記の新規化合物(V)および(VI)の構造における絶対配置は、炭素-炭素原子間または炭素-水素原子間の相関関係などをHMBC、DQFおよびNOEなどの種々のNMR測定結果に基づき決定した。さらに、配糖体部分を構成する糖は、酸加水分解後にHPLCにより同定した。 In addition, the absolute configuration in the structures of the novel compounds (V) and (VI) is based on various NMR measurement results such as HMBC, DQF and NOE based on the correlation between carbon-carbon atoms or carbon-hydrogen atoms. Were determined. Furthermore, the saccharide | sugar which comprises a glycoside part was identified by HPLC after acid hydrolysis.
以下に、新規化合物(V)および(VI)について得られた各種物理データを示す。
化合物(V) (ロベノサイドA)：
白色粉末
[α]D 29 -112.20° (c = 1.0、ピリジン)
高分解能陽イオンFAB-MS：計算値(C50H82O22)Na (M+Na)+：906.4828
実測値：906.4824
The various physical data obtained about the novel compounds (V) and (VI) are shown below.
Compound (V) (lovenoside A) :
White powder
[α] D 29 -112.20 ° (c = 1.0, pyridine)
High resolution cation FAB-MS: Calculated value (C 50 H 82 O 22 ) Na (M + Na) + : 906.4828
Actual value: 906.4824
IR (KBr、cm-1)：3450, 2941, 1626, 1470, 1280, 980
1H-NMR (500 MHz、ピリジン-ｄ5、δ(ppm))：0.82 (3H, d, J = 5.2 Hz, H-27), 0.99 (3H, s, H-18), 1.01 (3H, s, H-19), 1.18 (3H, d, J = 7.2 Hz, H-21), 3.98 (1H, brs, H-12), 5.34 (1H, d, J = 7.3 Hz, H-6), [4.93 (1H, d, J = 7.2 Hz, H-1')], [1.64 (3H, d, J = 6.0 Hz, H3-6''), 5.86 (1H, br s, H-1'') ], および[1.64 (3H, d, J = 6.0 Hz, H3-6'''), 6.40 (1H, br s, H-1''')]
IR (KBr, cm -1 ): 3450, 2941, 1626, 1470, 1280, 980
1 H-NMR (500 MHz, pyridine-d 5 , δ (ppm)): 0.82 (3H, d, J = 5.2 Hz, H-27), 0.99 (3H, s, H-18), 1.01 (3H, s, H-19), 1.18 (3H, d, J = 7.2 Hz, H-21), 3.98 (1H, brs, H-12), 5.34 (1H, d, J = 7.3 Hz, H-6), [4.93 (1H, d, J = 7.2 Hz, H-1 ')], [1.64 (3H, d, J = 6.0 Hz, H3-6''), 5.86 (1H, br s, H-1'' )], And [1.64 (3H, d, J = 6.0 Hz, H3-6 '''), 6.40 (1H, br s, H-1''')]
13C-NMR (125 MHz、ピリジン-ｄ5、δC(ppm)) ：37.4(C-1), 30.2(C-2), 78.1(C-3), 39.0(C-4), 140.9(C-5), 122.0(C-6), 32.4(C-7), 32.0(C-8), 44.5 (C-9), 37.0(C-10), 29.4(C-11), 71.4(C-12), 45.3(C-13), 48.2(C-14), 32.7(C-15), 79.2(C-16), 54.2(C-17), 17.3(C-18), 19.3(C-19), 42.0(C-20), 15.6(C-21), 98.5(C-22), 34.5(C-23), 30.8 (C-24), 31.3(C-25), 47.9(C-26), 19.7(C-27), 100.2(C-1'), 78.0(C-2'), 77.8(C-3'), 78.6(C-4'), 76.9(C-5'), 61.3(C-6'), 103.0(C-1''), 72.6(C-2''), 72.7(C-3''), 73.9(C-4''), 70.4(C-5''), 18.5(C-6''), (102.0(C-1'''), 72.6(C-2'''), 72.8(C-3'''), 74.2(C-4'''), 69.5(C-5'''), 18.7(C-6''')
陰イオンFAB-MS (m/z)：882 (M-H)-
陽イオンFAB-MS (m/z)：906 (M+Na)+
13 C-NMR (125 MHz, pyridine-d 5 , δ C (ppm)): 37.4 (C-1), 30.2 (C-2), 78.1 (C-3), 39.0 (C-4), 140.9 ( C-5), 122.0 (C-6), 32.4 (C-7), 32.0 (C-8), 44.5 (C-9), 37.0 (C-10), 29.4 (C-11), 71.4 (C -12), 45.3 (C-13), 48.2 (C-14), 32.7 (C-15), 79.2 (C-16), 54.2 (C-17), 17.3 (C-18), 19.3 (C- 19), 42.0 (C-20), 15.6 (C-21), 98.5 (C-22), 34.5 (C-23), 30.8 (C-24), 31.3 (C-25), 47.9 (C-26 ), 19.7 (C-27), 100.2 (C-1 '), 78.0 (C-2'), 77.8 (C-3 '), 78.6 (C-4'), 76.9 (C-5 '), 61.3 (C-6 '), 103.0 (C-1``), 72.6 (C-2''), 72.7 (C-3``), 73.9 (C-4''), 70.4 (C-5'' ), 18.5 (C-6 ''), (102.0 (C-1 '''), 72.6 (C-2'''), 72.8 (C-3 '''), 74.2 (C-4''' ), 69.5 (C-5 '''), 18.7 (C-6''')
Anion FAB-MS (m / z): 882 (MH) -
Cation FAB-MS (m / z): 906 (M + Na) +
化合物(VI) (ロベノサイドB)：
白色粉末
[α]D 29 -22.20° (c = 1.0、ピリジン).
高分解能陽イオンFAB-MS：計算値(C50H82O22)Na (M+Na)+：899.4783
実測地：899.4777
Compound (VI) (Lovenoside B) :
White powder
[α] D 29 -22.20 ° (c = 1.0, pyridine).
High resolution cation FAB-MS: Calculated value (C 50 H 82 O 22 ) Na (M + Na) + : 899.44783
Actual location: 899.4777
IR (KBr, cm-1)：3450, 2938, 1622, 1458, 1300, 980
1H-NMR (500 MHz、ピリジン-ｄ5、δ(ppm)) ：0.82 (3H, d, J = 5.2 Hz, H-27), 0.99 (3H, s, H-18), 1.01 (3H, s, H-19), 1.18 (3H, d, J = 7.2 Hz, H-21), 3.98 (1H, brs, H-12), 5.34 (1H, d, J = 7.3 Hz, H-6), [4.93 (1H, d, J = 7.2 Hz, H-1')], 5.12 (1H, br s, H-1''),および[1.65 (3H, d, J = 6.0 Hz, H3-6'''), 6.20 (1H, br s, H-1''')]
IR (KBr, cm -1 ): 3450, 2938, 1622, 1458, 1300, 980
1 H-NMR (500 MHz, pyridine-d 5 , δ (ppm)): 0.82 (3H, d, J = 5.2 Hz, H-27), 0.99 (3H, s, H-18), 1.01 (3H, s, H-19), 1.18 (3H, d, J = 7.2 Hz, H-21), 3.98 (1H, brs, H-12), 5.34 (1H, d, J = 7.3 Hz, H-6), [4.93 (1H, d, J = 7.2 Hz, H-1 ')], 5.12 (1H, br s, H-1''), and [1.65 (3H, d, J = 6.0 Hz, H3-6'''), 6.20 (1H, br s, H-1 ''')]
13C-NMR (125 MHz、ピリジン-ｄ5、δc(ppm)) ：37.5(C-1), 30.2(C-2), 77.7(C-3), 39.0(C-4), 141.2(C-5), 121.9(C-6), 32.5(C-7), 32.1(C-8), 44.5 (C-9), 37.0 (C-10), 29.4(C-11), 71.7(C-12), 45.3 (C-13), 48.2 (C-14), 32.7 (C-15), 78.8 (C-16), 54.2(C-17), 17.3(C-18), 19.3(C-19), 42.0(C-20), 15.5(C-21), 98.2(C-22), 34.5(C-23), 30.8 (C-24), 31.3(C-25), 48.0(C-26), 19.6(C-27), 100.5(C-1'), 76.3(C-2'), 70.3(C-4'), 85.0(C-3'), 75.0(C-5'), 62.5(C-6'), 105.7(C-1''), 75.0(C-2''), 78.5 (C-3''), 71.6(C-4''), 78.3(C-5''), 62.7(C-6''), 102.1(C-1'''), 72.5(C-2'''), 72.8 (C-3'''), 74.2 (C-4'''), 69.4(C-5'''), 18.6(C-6''')
陰イオンFAB-MS (m/z)：898 (M-H)-
陽イオンFAB-MS (m/z)：922 (M+Na)+
13 C-NMR (125 MHz, pyridine-d 5 , δc (ppm)): 37.5 (C-1), 30.2 (C-2), 77.7 (C-3), 39.0 (C-4), 141.2 (C -5), 121.9 (C-6), 32.5 (C-7), 32.1 (C-8), 44.5 (C-9), 37.0 (C-10), 29.4 (C-11), 71.7 (C- 12), 45.3 (C-13), 48.2 (C-14), 32.7 (C-15), 78.8 (C-16), 54.2 (C-17), 17.3 (C-18), 19.3 (C-19 ), 42.0 (C-20), 15.5 (C-21), 98.2 (C-22), 34.5 (C-23), 30.8 (C-24), 31.3 (C-25), 48.0 (C-26) , 19.6 (C-27), 100.5 (C-1 '), 76.3 (C-2'), 70.3 (C-4 '), 85.0 (C-3'), 75.0 (C-5 '), 62.5 ( C-6 '), 105.7 (C-1``), 75.0 (C-2''), 78.5 (C-3``), 71.6 (C-4''), 78.3 (C-5'') , 62.7 (C-6 ''), 102.1 (C-1 '''), 72.5 (C-2'''), 72.8 (C-3 '''), 74.2 (C-4'''), 69.4 (C-5 '''), 18.6 (C-6''')
Anion FAB-MS (m / z): 898 (MH) -
Cation FAB-MS (m / z): 922 (M + Na) +
乾燥ロボフルーツ含有成分の生理作用
次いで、本発明者は、得られたサポニン含有抽出物、溶出画分および精製画分について、これらの血糖値上昇抑制作用、胃粘膜保護作用および抗アレルギー作用に関して、各種活性試験を行った。
以下の各活性試験について、ラットまたはマウスを用いた試験結果をそれぞれ、以下の表に示す。
なお、各試験に用いたマウスの数を各表中「ｎ」として示している。
Physiological effects of drying Lobo fruit containing component and then, the inventors obtained saponin containing extracts, the elution fraction and purified fractions, these blood glucose increase inhibitory effect, with respect to the gastric mucosa protective activity and antiallergic activity, Various activity tests were performed.
For the following activity tests, the test results using rats or mice are shown in the following tables, respectively.
The number of mice used in each test is indicated as “n” in each table.
試験例１
血糖値上昇抑制効果の測定方法：
約24時間絶食させたWistar系雄性ラット(体重約130〜140 g)を、コントロール(正常)群、コントロール(糖負荷)群および被験試料投与群として、それぞれの投与試験に用いた。以下の表に示したロボフルーツのMeOHエキスを被験物質として、各規定量をアラビアゴム末の5％水溶液に懸濁させて被験試料とし、各群のラットに経口投与した。被験試料の投与30分後に、ショ糖1.0 g/kgの割合となるように、ショ糖水溶液を各群のラットにそれぞれ経口投与した。
Test example 1
Measuring method of blood glucose level rise suppression effect :
Wistar male rats (body weight: about 130 to 140 g) fasted for about 24 hours were used for each administration test as a control (normal) group, a control (sugar load) group, and a test sample administration group. Each prescribed amount was suspended in a 5% aqueous solution of gum arabic powder as a test sample using the Robofruit MeOH extract shown in the following table as a test substance, and orally administered to each group of rats. Thirty minutes after administration of the test sample, an aqueous sucrose solution was orally administered to each group of rats so that the ratio of sucrose was 1.0 g / kg.
なお、コントロール(正常)群には、アラビアゴム末の5％水溶液および水のみを投与した。
また、コントロール(糖負荷)群には、アラビアゴム末の5％水溶液および上記の割合でショ糖を投与した。
ショ糖の投与30、60および120分後に、エーテル麻酔下に、ラットの眼窩静脈より採血し、血液を遠心分離(5000 rpm、10分)して分離した血清を用いて、グルコースオキシダーゼ法(グルコースCIIテストワコー、和光純薬)により血清中のグルコース濃度を測定した結果を以下の表に示す。
In the control (normal) group, only a 5% aqueous solution of gum arabic powder and water were administered.
The control (sugar load) group was administered with a 5% aqueous solution of gum arabic powder and sucrose at the above ratio.
30, 60, and 120 minutes after administration of sucrose, blood was collected from the orbital vein of rats under ether anesthesia, and the blood was collected by centrifugation (5000 rpm, 10 minutes). The following table shows the results of measurement of glucose concentration in serum by CII Test Wako, Wako Pure Chemicals).
本発明者は、さらに前記のMeOH溶出部の各精製画分についても同様の血糖値降下作用を測定したところ、サポニン含有精製画分が、意外にも強力な血糖値上昇抑制効果を有することを見出した。 The inventor further measured the blood glucose level lowering action for each of the purified fractions of the MeOH elution part, and found that the saponin-containing purified fraction has a surprisingly strong blood glucose level increase suppressing effect. I found it.
試験例２
そこで、本発明者は、上記と全く同様にして、単離した化合物(III)および化合物(IV)について血糖値上昇抑制作用を測定した結果を、以下の表に示す。
Test example 2
Accordingly, the present inventors show the results of measuring the inhibitory action on the increase in blood glucose level for the isolated compound (III) and compound (IV) in exactly the same manner as described above, and the results are shown in the following table.
試験例２
胃粘膜保護作用
次いで、発明者は、前記で得られたサポニン含有抽出物、溶出画分および精製画分について、これらの胃粘膜保護作用、すなわち、エタノール誘発胃粘膜損傷抑制作用およびインドメタシン誘発胃粘膜損傷抑制作用に関して調べた。
Test example 2
Gastric mucosal protective action Next, the inventor used the saponin-containing extract obtained above, the eluted fraction and the purified fraction to protect these gastric mucosa, ie, the ethanol-induced gastric mucosal damage inhibitory action and the indomethacin-induced gastric mucosa. The damage suppression effect was examined.
エタノール誘発胃粘膜損傷抑制効果の測定方法：
24時間絶食させたSprague-Dowley系雄性ラット(体重約230〜260 g)を、コントロール(正常)群、および被験試料投与群として、それぞれの投与試験に用いた。
被験試料投与群には、エタノールの経口投与の１時間前に、前記で得られたメタノール溶出画分、アセトン溶出画分およびH2O溶出画分の濃縮物を被験物質とし、各被験物質をアラビアゴム末の5％水溶液に懸濁させて被験試料とし、各群のラットに被験物質100 mg/kg割合となるように経口投与した。
Method for measuring the effect of ethanol-induced gastric mucosa damage inhibition
Sprague-Dowley male rats (body weight: about 230 to 260 g) fasted for 24 hours were used as a control (normal) group and a test sample administration group in each administration test.
In the test sample administration group, 1 hour before oral administration of ethanol, the methanol elution fraction, the acetone elution fraction and the H 2 O elution fraction obtained above were used as test substances. It was suspended in a 5% aqueous solution of gum arabic powder as a test sample and orally administered to each group of rats at a test substance concentration of 100 mg / kg.
なお、コントロール(正常)群には、アラビアゴム末の5％水溶液のみを投与した。
各ラット１匹につき、エタノール1.5 mlを経口投与し、その１時間後に胃を摘出し、1.5％ホルマリンで固定した後、胃を切り開き、胃粘膜に発生した全損傷部の長さの計(mm、損傷長)を測定して得られた結果を、以下の表に示す。
In the control (normal) group, only a 5% aqueous solution of gum arabic powder was administered.
For each rat, 1.5 ml of ethanol was orally administered, and after 1 hour, the stomach was removed and fixed with 1.5% formalin. Then, the stomach was opened, and the total length of the damaged part (mm) The results obtained by measuring the (damage length) are shown in the following table.
試験例４
そこで、本発明者は、さらに上記のMeOH溶出画分の各精製画分についても同様の血糖値降下効果を測定したところ、サポニン含有精製画分が、意外にも強力なエタノール誘発胃粘膜損傷抑制作用を有することを見出した。
そこで、本発明者は、上記と全く同様にして、単離した化合物(III)および化合物(IV)についてエタノール誘発胃粘膜損傷抑制作用を測定した結果を、以下の表に示す。
Test example 4
Therefore, the present inventor further measured the blood glucose level lowering effect for each of the purified fractions of the MeOH-eluted fraction, and the saponin-containing purified fraction was surprisingly powerful in suppressing ethanol-induced gastric mucosal damage. It was found to have an action.
Therefore, the present inventor measured the ethanol-induced gastric mucosal damage inhibitory action of the isolated compound (III) and compound (IV) in exactly the same manner as described above, and the results are shown in the following table.
試験例５
そこで、本発明者は、同様に、本発明の組成物のインドメタシン誘発胃粘膜損傷抑制作用についても調べた。
すなわち、24時間絶食させたSprague-Dowley系雄性ラット(体重約230〜260 g)を、コントロール(正常)群、および被験試料投与群として、それぞれの投与試験に用いた。
被験試料投与群には、インドメタシン(20 mg/kg)の経口投与の１時間前に、前記で得られたメタノール溶出画分、アセトン溶出画分およびH2O溶出画分の濃縮物を被験物質とし、各被験物質をアラビアゴム末の5％水溶液に懸濁させて被験試料とし、各群のラットに被験物質100 mg/kg割合となるように経口投与した。
Test Example 5
Therefore, the present inventor similarly examined the inhibitory action of indomethacin-induced gastric mucosa damage of the composition of the present invention.
That is, Sprague-Dowley male rats (body weight: about 230 to 260 g) fasted for 24 hours were used for each administration test as a control (normal) group and a test sample administration group.
In the test sample administration group, concentrates of the methanol-eluted fraction, acetone-eluted fraction and H 2 O-eluted fraction obtained above were tested one hour before oral administration of indomethacin (20 mg / kg). Each test substance was suspended in a 5% aqueous solution of gum arabic powder to give a test sample, which was orally administered to each group of rats at a test substance concentration of 100 mg / kg.
なお、コントロール(正常)群には、アラビアゴム末の5％水溶液のみを投与した。
各ラットに、インドメタシン (20 mg/kg)を経口投与し、その4時間後に胃を摘出し、1.5％ホルマリンで固定した後、胃を切り開き、胃粘膜に発生した全損傷部の長さの計(mm、損傷長)を測定して得られた結果を、以下の表に示す。
In the control (normal) group, only a 5% aqueous solution of gum arabic powder was administered.
Indomethacin (20 mg / kg) was orally administered to each rat, and after 4 hours, the stomach was removed and fixed with 1.5% formalin, then the stomach was opened, and the total length of all injuries in the gastric mucosa was measured. The results obtained by measuring (mm, damage length) are shown in the following table.
試験例６
そこで、本発明者は、さらに上記のMeOH溶出画分の各精製画分についても同様の血糖値降下効果を測定したところ、サポニン含有精製画分が、意外にも強力なインドメタシン誘発胃粘膜損傷抑制作用を有することを見出した。
そこで、本発明者は、上記と全く同様にして、単離した化合物(III)および化合物(IV)についてインドメタシン誘発胃粘膜損傷抑制作用を測定した結果を、以下の表に示す。
Test Example 6
Therefore, the present inventor further measured the blood glucose level lowering effect for each of the purified fractions of the MeOH-eluted fraction, and the saponin-containing purified fraction was surprisingly powerful in suppressing indomethacin-induced gastric mucosal damage. It was found to have an action.
Therefore, the present inventor measured the indomethacin-induced gastric mucosal damage inhibitory action of the isolated compound (III) and compound (IV) in exactly the same manner as described above, and the results are shown in the following table.
試験例７
アレルギー抑制作用
次いで、発明者は、前記で得られたサポニン含有抽出物、溶出画分および精製画分について、これらのアレルギー抑制作用に関して調べた。
Test Example 7
Allergy inhibition Then, the inventors saponin-containing extract obtained in the above, the elution fraction and the purified fraction was examined for these allergy suppressing action.
アレルギー抑制抑制作用の測定方法：
ddYマウス(体重約25〜30 g)を、コントロール(正常)群、コントロール(対照)群および被験試料投与群として、それぞれの投与試験に用いた。
すなわち、マウスの両耳のそれぞれに抗ＤＮＰ ＩｇＥ抗体（20μg/mlを10μl）を皮内注射した。被験試料投与群のマウスには、投与47時間後に、被験試料を経口投与した。
Method for measuring allergy suppression inhibitory action :
ddY mice (body weight of about 25-30 g) were used for each administration test as a control (normal) group, a control (control) group, and a test sample administration group.
That is, anti-DNP IgE antibody (20 μg / ml in 10 μl) was injected intradermally into each of both ears of mice. The test sample was orally administered to the mice in the test sample administration group 47 hours after administration.
次いで、全マウスに、ジニトロフェニル化した牛血清アルブミン0.25 mgを含む2.0％エバンスブルー溶液0.25 mlを静脈内投与した。その0.5時間後、各マウスの両耳を切除し、１ N KOH水溶液0.5 mlに37℃で一夜溶解した。これに、0.6 N H3PO4溶液およびアセトンの混液(5：13)4.5 mlを加えて、遠心分離（4000 rpm、10分間）し、上清の吸光度（波長620 nm）を測定した。 All mice were then intravenously administered with 0.25 ml of a 2.0% Evans blue solution containing 0.25 mg of dinitrophenylated bovine serum albumin. After 0.5 hour, both ears of each mouse were excised and dissolved in 0.5 ml of 1 N KOH aqueous solution at 37 ° C. overnight. To this, 4.5 ml of a mixture of 0.6 NH 3 PO 4 solution and acetone (5:13) was added, centrifuged (4000 rpm, 10 minutes), and the absorbance (wavelength 620 nm) of the supernatant was measured.
先ず、本発明者は、実施例１で得られたサポニン含有MｅOHエキスのアレルギー抑制作用について調べた結果、該エキスは投与量依存性アレルギー抑制効果を有することが判明した。
次いで、本発明者は、上記ＭｅＯＨエキスのH2O溶出画分とＭｅＯＨ溶出画分とについて同様に、アレルギー抑制作用について調べた結果、ＭｅＯＨ溶出画分が投与量依存性アレルギー抑制効果を有することが判明した。
First, as a result of examining the allergic inhibitory action of the saponin-containing MeOH extract obtained in Example 1, the present inventor was found to have a dose-dependent allergic inhibitory effect.
Subsequently, as a result of examining the allergy suppressing action of the MeOH extract similarly to the H 2 O elution fraction and the MeOH elution fraction of the above MeOH extract, the MeOH elution fraction has a dose-dependent allergy suppressing effect. There was found.
そこで、本発明者は、さらに、化合物(III)および化合物(IV)について、同様に、アレルギー抑制作用について調べた結果、化合物(III)および化合物(IV)が共に、投与量依存性アレルギー抑制効果を有することが判明した。以上の結果を、以下の表に示す。 Therefore, the present inventor further investigated the allergy inhibitory action of compound (III) and compound (IV), and as a result, both of compound (III) and compound (IV) were dose-dependent allergic inhibitory effect. It was found to have The above results are shown in the following table.
実施例２
当該分野で公知の方法にしたがって、本発明によるサポニン含有濃縮物10重量部を乳糖25重量部と混合し、ゼラチンカプセルに充填し、１カプセル中に抽出物が50 mg含有されるゼラチンカプセル剤を得た。
Example 2
According to a method known in the art, 10 parts by weight of the saponin-containing concentrate according to the present invention is mixed with 25 parts by weight of lactose, filled into gelatin capsules, and gelatin capsules containing 50 mg of extract in one capsule are obtained. Obtained.
実施例３
実施例1で得られたMeOH溶出画分を実施例２の濃縮物に替えて、実施例２と同様にして、ゼラチンカプセル剤を得た。
Example 3
The MeOH elution fraction obtained in Example 1 was replaced with the concentrate of Example 2, and gelatin capsules were obtained in the same manner as in Example 2.
実施例４
実施例１で得られたFr. 9の画分を実施例２の濃縮物に替えて、実施例２と同様にして、ゼラチンカプセル剤を得た。
Example 4
The Fr. 9 fraction obtained in Example 1 was replaced with the concentrate of Example 2, and gelatin capsules were obtained in the same manner as in Example 2.
本発明によれば、ロボフルーツを水または含水低級アルコールで抽出したサポニン含有抽出物もしくはその濃縮物または該サポニン含有精製画分を有効成分として含み、血糖値上昇抑制、胃粘膜保護またはアレルギー抑制に用いられ得る医薬組成物が提供される。また、該組成物が含有される健康食品が提供される。 According to the present invention, a saponin-containing extract obtained by extracting robofruit with water or a hydrous lower alcohol, or a concentrate thereof, or a purified fraction containing the saponin as an active ingredient, can be used to suppress an increase in blood glucose level, protect gastric mucosa, or suppress allergy. Pharmaceutical compositions that can be used are provided. In addition, a health food containing the composition is provided.
Claims (4)
β-ヒドロキシ基である］
で表されるサポニンを有効成分として含む、請求項１に記載の医薬組成物。 Formula (I):
The pharmaceutical composition of Claim 1 which contains the saponin represented by these as an active ingredient.
で表されるサポニン。 General formula:
Saponin represented by
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