JP2013253040A - Adiponectin production promoter - Google Patents
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- JP2013253040A JP2013253040A JP2012129685A JP2012129685A JP2013253040A JP 2013253040 A JP2013253040 A JP 2013253040A JP 2012129685 A JP2012129685 A JP 2012129685A JP 2012129685 A JP2012129685 A JP 2012129685A JP 2013253040 A JP2013253040 A JP 2013253040A
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Abstract
Description
本発明は、新規なアディポネクチンの産生促進剤又はそれらを含有する医薬品若しくは飲食品等に関する。さらに詳しくは、該アディポネクチン産生促進剤を含有する、血中のアディポネクチン濃度の低下に起因する各種疾病の予防又は改善に効果を発揮し得る医薬又は飲食品等に関する。 The present invention relates to a novel adiponectin production promoter or a pharmaceutical or a food or drink containing the same. More specifically, the present invention relates to a drug or food / drink that contains the adiponectin production promoter and can exert an effect on prevention or improvement of various diseases caused by a decrease in blood adiponectin concentration.
現代社会において、肥満を始め、動脈硬化や脂肪肝、糖尿病など様々な疾病が大きな問題となっている。これらの疾病の治療には、従来から薬物治療が行われており、様々な治療薬が知られている。しかしながら、薬剤の服用により高血圧、肝障害、下痢、便秘、頭痛などの副作用を伴うことがあり、患者への負担が大きい。したがって、近年では、日常の食生活を通じて、肥満、動脈硬化、脂肪肝、糖尿病などの疾病を予防もしくは改善しようとする様々な方法が検討されている。例えば、脂肪分解促進剤や食物繊維の摂取などが挙げられるが、依然として、より有効な方法が求められている。 In modern society, various diseases such as obesity, arteriosclerosis, fatty liver and diabetes have become major problems. For the treatment of these diseases, drug treatment has been conventionally performed, and various therapeutic agents are known. However, taking the drug may cause side effects such as hypertension, liver damage, diarrhea, constipation, and headache, which is a heavy burden on the patient. Therefore, in recent years, various methods for preventing or ameliorating diseases such as obesity, arteriosclerosis, fatty liver, and diabetes have been studied through daily eating habits. For example, intake of a lipolysis promoter or dietary fiber can be mentioned, but a more effective method is still required.
アディポネクチンは、脂肪細胞から特異的に分泌されるタンパク質であり、肥満、動脈硬化、脂肪肝、糖尿病などの疾病に密接に関与していることが明らかとなってきている。実際に、肥満や、糖尿病などの患者では、血中のアディポネクチン濃度が低下していることが報告されており、低アディポネクチン血症という新しい概念の疾患として認識されている（非特許文献１〜３を参照）。また、血中のアディポネクチン濃度を増加させることによって、糖尿病等の生活習慣病を改善できることが、医学的に示されている（非特許文献４を参照）。 Adiponectin is a protein that is specifically secreted from adipocytes and has been shown to be closely related to diseases such as obesity, arteriosclerosis, fatty liver, and diabetes. Actually, it has been reported that the adiponectin concentration in blood is decreased in patients such as obesity and diabetes, and it is recognized as a disease of a new concept of hypoadiponectinemia (Non-Patent Documents 1 to 3). See). It has also been medically shown that lifestyle diseases such as diabetes can be improved by increasing the concentration of adiponectin in the blood (see Non-Patent Document 4).
したがって、発明が解決しようとする課題は、肥満、動脈硬化、脂肪肝、糖尿病などの疾病を予防又は改善することを目的として、アディポネクチンの産生を促進し、血中のアディポネクチン濃度を増加させることができ、且つ副作用の少ない機能性成分を提供することにある。更には、当該機能成分を含有する医薬品、飲食品等を提供することにある。 Therefore, the problem to be solved by the invention is to promote the production of adiponectin and increase the concentration of adiponectin in the blood for the purpose of preventing or ameliorating diseases such as obesity, arteriosclerosis, fatty liver and diabetes. An object of the present invention is to provide a functional ingredient that can be used and has few side effects. Furthermore, it is providing the pharmaceutical, food-drinks, etc. containing the said functional component.
本発明者らは、上記課題を解決するために鋭意検討を行った結果、アスパラガス又はアスパラガスから抽出された成分がアディポネクチンの分泌を誘導することを見出して、本発明を完成するに至った。 As a result of intensive studies to solve the above problems, the present inventors have found that asparagus or a component extracted from asparagus induces secretion of adiponectin, and have completed the present invention. .
すなわち、本発明は以下の通りである。
1） アスパラガス又はアスパラガスから抽出された抽出物を有効成分として含有することを特徴とするアディポネクチン産生促進剤。
2） 1）に記載のアディポネクチン産生促進剤を含有することを特徴とする医薬品又は飲食品。
That is, the present invention is as follows.
1) An adiponectin production promoter characterized by containing asparagus or an extract extracted from asparagus as an active ingredient.
2) A pharmaceutical or food or drink comprising the adiponectin production promoter described in 1).
アスパラガス又はアスパラガスから抽出された抽出物は、脂肪細胞におけるアディポネクチンの産生を促進することが示された。また、アスパラガス又はアスパラガスから抽出された抽出物は天然物由来の物質であるため、副作用の危険性が低いことが期待される。 Asparagus or extracts extracted from asparagus have been shown to promote the production of adiponectin in adipocytes. Moreover, since the extract extracted from asparagus or asparagus is a substance derived from a natural product, it is expected that the risk of side effects is low.
本発明について、以下に詳細に説明する。 The present invention will be described in detail below.
本発明のアディポネクチン産生促進剤は、アスパラガス又はアスパラガスから抽出された抽出物を含有することを特徴とする。 The adiponectin production promoter of the present invention is characterized by containing asparagus or an extract extracted from asparagus.
アスパラガスはユリ科またはクサスギカズラ科のアスパラガス属で雌雄異株である。市場ではグリーンアスパラガスとホワイトアスパラガスがあるが、品種は同一である。本出願における使用部位は、好ましくは通常食用に供される若茎である。更に、上記アスパラガス原料はそのまま使用してもよく、あるいは、必要に応じて適度に乾燥させてから用いてもよい。また、抽出の際は、抽出効率を向上させるために、上記アスパラガス原料の全体若しくは一部又はその乾燥物を適度に切断若しくは粉砕することが好ましい。 Asparagus is a genus asparagus belonging to the genus Asparagus belonging to the family Lilyaceae or the family Cyprus. There are green asparagus and white asparagus in the market, but the varieties are the same. The use site in the present application is preferably a young stalk that is usually used for food. Furthermore, the asparagus raw material may be used as it is, or may be used after being appropriately dried as required. In the extraction, it is preferable to appropriately cut or pulverize the whole or a part of the asparagus raw material or a dried product thereof in order to improve the extraction efficiency.
アスパラガスから抽出された抽出物を取得するにあたって、その抽出の方法、条件については特に限定はなく、必要に応じて種々の抽出方法、抽出条件とすることができる。抽出溶媒としては、水、１価アルコール（エタノール、メタノール、プロパノール、ブタノール等）、多価アルコール（グリセリン、１，３−ブチレングリコール、プロピレングリコール等）、酢酸エチル等の酢酸エステル、アセトン等の親水性有機溶媒が挙げられる。尚、本明細書中の「水」には、特段の記載がない限り、加熱した水（通常３０〜１００℃、好ましくは４０〜１００℃、更に好ましくは５０〜９０℃、特に好ましくは温度５０〜７０℃の温水又は７０℃を超えて１００℃以下の熱水）も含む。また、抽出溶媒としては、上記親水性有機溶媒と水との混合溶媒でもよい。かかる混合溶媒として例えば、水／１価アルコール（エタノール及びメタノール等）、又は水／多価アルコール（グリセリン、１，３−ブチレングリコール及びプロピレングリコール等）の混合溶媒等が挙げられる。もっとも、本発明のアディポネクチン分泌促進剤は、生体に対して用いる素材であることから、生体に刺激を及ぼさないような溶媒を用いることが好ましい。かかる溶媒としては、水、エタノール、及び水／エタノールの混合溶媒が挙げられる。 In obtaining the extract extracted from asparagus, the extraction method and conditions are not particularly limited, and various extraction methods and extraction conditions can be used as necessary. Extraction solvents include water, monohydric alcohols (ethanol, methanol, propanol, butanol, etc.), polyhydric alcohols (glycerin, 1,3-butylene glycol, propylene glycol, etc.), acetates such as ethyl acetate, and hydrophilic substances such as acetone. Organic solvents may be mentioned. In the present specification, unless otherwise specified, “water” is heated water (usually 30 to 100 ° C., preferably 40 to 100 ° C., more preferably 50 to 90 ° C., particularly preferably 50 ° C.). Hot water of ˜70 ° C. or hot water of over 70 ° C. and 100 ° C. or less). In addition, the extraction solvent may be a mixed solvent of the hydrophilic organic solvent and water. Examples of such a mixed solvent include water / monohydric alcohol (ethanol, methanol, etc.) or water / polyhydric alcohol (glycerin, 1,3-butylene glycol, propylene glycol, etc.). But since the adiponectin secretion promoter of this invention is a raw material used with respect to a biological body, it is preferable to use the solvent which does not irritate | stimulate a biological body. Such solvents include water, ethanol, and water / ethanol mixed solvents.
抽出方法としては、常温ホモジナイズ抽出、還流抽出、超臨界流体抽出等が挙げられる。非振盪下で行ってもよく、振盪下で行ってもよい。また、抽出温度としては、常温抽出の場合、通常、０℃以上、好ましくは１０℃〜３０℃、更に好ましくは２０〜３０℃とすることができる。また、加熱抽出の場合は３０℃を超え１５０℃以下、好ましくは６０〜１３０℃、更に好ましくは８０〜１００℃とすることができる。更に、抽出時間は通常１０分以上、好ましくは、非振盪下又は常温抽出の場合、１時間〜１０日間、振盪下又は加熱抽出の場合、３０分〜２４時間、更に好ましくは、振盪下又は常温抽出の場合、５時間〜７日間、振盪下又は加熱抽出の場合、１〜１２時間、より好ましくは、振盪下又は常温抽出の場合、１０時間〜３日間、振盪下又は加熱抽出の場合、３〜１０時間である。 Examples of the extraction method include normal temperature homogenization extraction, reflux extraction, supercritical fluid extraction, and the like. It may be performed under non-shaking or may be performed under shaking. Moreover, as extraction temperature, in normal temperature extraction, it is 0 degreeC or more normally, Preferably it is 10 to 30 degreeC, More preferably, it can be 20 to 30 degreeC. Moreover, in the case of heat extraction, it can exceed 30 degreeC and 150 degrees C or less, Preferably it is 60-130 degreeC, More preferably, it can be set as 80-100 degreeC. Further, the extraction time is usually 10 minutes or more, preferably 1 hour to 10 days in the case of non-shaking or room temperature extraction, 30 minutes to 24 hours in the case of shaking or heating extraction, more preferably under shaking or room temperature. In the case of extraction, 5 hours to 7 days, in the case of shaking or heating extraction, 1 to 12 hours, more preferably in the case of shaking or room temperature extraction, 10 hours to 3 days, in the case of shaking or heating extraction, 3 -10 hours.
尚抽出は、同一原料について１回のみ行ってもよいが、２回以上繰り返して行ってもよく、一度抽出を行って得られた抽出物について、必要に応じて、再度水、エタノール、酢酸エチル、又は水／エタノール等の溶媒で抽出を行ってもよい。この場合の再度の抽出は、前の抽出と同様に行ってもよく、あるいは、異なる抽出方法、抽出条件で行ってもよい。また、上記抽出により得られた抽出物について、必要に応じてろ過を行って莢雑物を除いたり、濃縮したりすることにより、有効成分濃度を高めることができる。この濃縮の方法については特に限定はなく、加温によって濃縮する他、低温又は加温下、減圧により濃縮することができる。尚、この濃縮は、抽出物が乾固するまで行ってもよい。また、濃縮する場合、抽出物自体ではなく、抽出物をろ過して得られたろ液を濃縮してもよい。
The extraction may be performed only once for the same raw material, but may be repeated twice or more. If necessary, the extract obtained by performing the extraction once again with water, ethanol, ethyl acetate. Alternatively, extraction may be performed with a solvent such as water / ethanol. The re-extraction in this case may be performed in the same manner as the previous extraction, or may be performed with a different extraction method and extraction condition. Moreover, about the extract obtained by the said extraction, an active ingredient density | concentration can be raised by filtering as needed and removing a contaminant or concentrating. There is no particular limitation on the concentration method, and it can be concentrated by heating, or can be concentrated by reducing the pressure at low temperature or under heating. This concentration may be performed until the extract is dried. Moreover, when concentrating, you may concentrate not the extract itself but the filtrate obtained by filtering an extract.
本発明のアディポネクチン産生促進剤若しくはそれらを含有する医薬品又は飲食品等の形態について特に限定はない。例えば、液状（必要に応じて脱色等の後処理をした液も含む。）でもよいし、液状物を濃縮した濃縮液でもよい。また、その他にも、噴霧式乾燥や凍結乾燥等の公知の方法により溶媒を除去した固形物や粉末化した粉末物でもよい。その他、液状、粉末品、造粒等により得られる造粒品、打錠成形等により得られる錠剤、及びマイクロカプセル等が挙げられる。 There are no particular limitations on the form of the adiponectin production promoter of the present invention or the pharmaceutical or food / beverage products containing them. For example, it may be a liquid (including a liquid after-treatment such as decolorization as necessary) or a concentrated liquid obtained by concentrating a liquid. In addition, a solid or powdered powder from which the solvent has been removed by a known method such as spray drying or freeze drying may be used. Other examples include liquid products, powder products, granulated products obtained by granulation, tablets obtained by tableting and the like, and microcapsules.
本発明のアディポネクチン産生促進剤を医薬品として使用する場合、例えば、錠剤、カプセル剤、散剤、顆粒剤、シロップ剤などの経口用製剤、又は坐剤、外用剤などの非経口剤として製剤化できる。 When the adiponectin production promoter of the present invention is used as a pharmaceutical, it can be formulated as an oral preparation such as a tablet, capsule, powder, granule or syrup, or a parenteral preparation such as a suppository or external preparation.
本発明の医薬品の１日あたりの摂取量としては、年齢、性別、体重などを考慮して適宜増減できるが、アスパラガスとして１回１０〜１００００ｇを１日１回又は数回に分けて摂取することができるようにすればよい。 The daily intake of the pharmaceutical product of the present invention can be appropriately increased or decreased in consideration of age, sex, body weight, etc., but asparagus is taken 10 to 10,000 g at a time, once a day or divided into several times. You can do that.
本発明のアディポネクチン産生促進剤を飲食品に添加することにより、その飲食品にアディポネクチン産生促進活性を付与することが可能となる。添加されるべき食品は特に限定されない。 By adding the adiponectin production promoter of the present invention to a food or drink, it becomes possible to impart adiponectin production promoting activity to the food or drink. The food to be added is not particularly limited.
本発明の別の態様によれば、本発明による飲食品は、血中のアディポネクチン濃度の低下に起因する疾病もしくは状態を予防又は改善する機能を有し、その機能表示が付されたものである。 According to another aspect of the present invention, the food or drink according to the present invention has a function of preventing or ameliorating a disease or condition caused by a decrease in the concentration of adiponectin in the blood, and the function indication is attached. .
また、本発明のアディポネクチン産生促進剤は、特定保健用食品（健康増進法（平成１４年法律第１０３号）第２６条第１項の許可又は第２９条第１項の承認を受け、「食生活において特定の保健の目的で摂取する者に対し、その摂取により当該保健の目的が期待できる旨の表示をする食品」）として特定の用途表記を付して提供することも可能である。 In addition, the adiponectin production promoter of the present invention is a food for specified health use (approved under Article 26, Paragraph 1 of the Health Promotion Act (Act No. 103 of 2002) or approved under Article 29, Paragraph 1). It is also possible to provide a person who ingests for a specific health purpose in daily life with a specific usage notation as “a food that indicates that the purpose of the health can be expected by ingestion”.
また本発明のアディポネクチン産生促進剤若しくはそれらを含有する医薬品又は飲食品は、アディポネクチン産生促進を阻害しない限り、ビタミン、アミノ酸、ミネラル、生薬及びその抽出物等を配合することができる。そして、賦形剤、崩壊剤、結合剤、滑沢剤、抗酸化剤、コーティング剤、着色剤、矯味矯臭剤などを配合し、さらに必要に応じてｐＨ調整剤、清涼化剤、懸濁化剤、消泡剤、粘稠剤、溶解補助剤、界面活性剤、香料などの１種又は２種以上を必要に応じて適宜配合してもよい。例えば、本発明のアディポネクチン産生促進剤若しくはそれらを含有する医薬品又は飲食品等が粉末品、造粒品の場合、製造における計量を容易にするために、ラクトース、デキストロース、サッカロース、セルロース、トウモロコシ澱粉及びジャガイモ澱粉等の増量剤等を添加することができる。また、シリカ、タルク、ステアリン酸、ステアリン酸マグネシウム、ステアリン酸カルシウム及びポリエチレングリコール等の滑沢剤、デンプン、アラビアゴム、ゼラチン、メチルセルロース、カルボキシメチルセルロース、及びポリビニルピロリジン等の結合剤、デンプン、アルギン酸、アルギン酸塩、及びグリコール酸デンプンナトリウム等の崩壊剤、発泡剤、色素、甘味料、例えばレシチン、ポリソルベート、ラウリル硫酸塩等の湿潤剤、及び一般に非毒性で医薬的処方に用いられる薬学的に非活性な物質を含んでもよい。その他の薬効成分を含んでいてもよい。 In addition, the adiponectin production promoter of the present invention or a pharmaceutical or food or drink containing them can contain vitamins, amino acids, minerals, herbal medicines, extracts thereof, and the like as long as they do not inhibit the promotion of adiponectin production. Then, excipients, disintegrants, binders, lubricants, antioxidants, coating agents, coloring agents, flavoring agents, etc. are blended, and pH adjusters, cooling agents, suspending agents are added as necessary. You may mix | blend suitably 1 type, or 2 or more types, such as an agent, an antifoamer, a thickener, a solubilizing agent, surfactant, and a fragrance | flavor as needed. For example, when the adiponectin production promoter of the present invention or a pharmaceutical or food and drink containing the same is a powdered product or a granulated product, lactose, dextrose, saccharose, cellulose, corn starch and Bulking agents such as potato starch can be added. Also, lubricants such as silica, talc, stearic acid, magnesium stearate, calcium stearate and polyethylene glycol, binders such as starch, gum arabic, gelatin, methylcellulose, carboxymethylcellulose and polyvinylpyrrolidine, starch, alginic acid, alginate , And disintegrants such as sodium starch glycolate, foaming agents, pigments, sweeteners such as lecithins, polysorbates, wetting agents such as lauryl sulfate, and generally non-toxic, pharmaceutically inactive substances used in pharmaceutical formulations May be included. It may contain other medicinal ingredients.
本発明のアディポネクチン産生促進剤は、上記のように医薬品又は飲食品等として利用する以外にも、例えばアディポネクチン産生促進作用を有する新たな成分を探索するための「ポジティブコントロール」として使用することが可能である。 The adiponectin production promoter of the present invention can be used as, for example, a “positive control” for searching for a new component having an adiponectin production promoting action, in addition to being used as a pharmaceutical or a food or drink as described above. It is.
＜試験試料の調製＞
被験物質は以下の方法により調製した。
<Preparation of test sample>
The test substance was prepared by the following method.
原料となる野菜（1〜4 kg）を破砕後、加温しながら水で抽出した。固形分も搾汁した後、抽出液と合わせて金属ストレーナーで濾した。さらに減圧下で濃縮し、高温による殺菌を行った。さらに濾過・濃縮および殺菌の工程を繰り返し、検体のエキス（500 g）を得た。検体のエキスを凍結乾燥して粉末状の被験物質とした。
＜アディポネクチン産生促進作用の評価＞
試験例1 3T3-L1細胞（DSファーマ）を1×104の細胞数で96well plateに播種し、その2日後から分化誘導培地（F-DM-2-L1）で2日間培養した。その後、脂肪細胞用培地（F-AM-1-L1）で培養し、2日毎に培地を交換した。分化誘導21日後に被験物質を、終濃度が125μg/mLになるよう培地に添加し、24時間培養した後、培地中のアディポネクチン量を、マウス／ラットアディポネクチンELISAキット（岩井化学薬品）を用いて測定した。被験物質を添加しない状態のアディポネクチン量（比較例1）を100%として、各被験物質のアディポネクチン産生促進率を算出した（表1）。
Vegetables (1 to 4 kg) as raw materials were crushed and extracted with water while heating. The solid content was also squeezed and then combined with the extract and filtered with a metal strainer. Furthermore, it concentrated under reduced pressure and sterilized by high temperature. Further, filtration, concentration and sterilization steps were repeated to obtain a specimen extract (500 g). The specimen extract was freeze-dried to obtain a powdery test substance.
<Evaluation of adiponectin production promoting action>
Test Example 1 3T3-L1 cells (DS Pharma) were seeded on a 96-well plate at a cell count of 1 × 10 4 , and cultured for 2 days in differentiation induction medium (F-DM-2-L1) 2 days later. Thereafter, the cells were cultured in an adipocyte medium (F-AM-1-L1), and the medium was changed every two days. 21 days after differentiation induction, the test substance is added to the medium so that the final concentration is 125 μg / mL, and cultured for 24 hours. It was measured. The adiponectin production promotion rate of each test substance was calculated with the amount of adiponectin in the state where no test substance was added (Comparative Example 1) as 100% (Table 1).
その結果、アスパラガスエキス（実施例）はアディポネクチンを産生させることが分かった。一方、比較例2〜５の各食品エキスには明確なアディポネクチン産生促進活性は認められなかった（表１）。 As a result, it was found that the asparagus extract (Example) produces adiponectin. On the other hand, no clear adiponectin production promoting activity was observed in each food extract of Comparative Examples 2 to 5 (Table 1).
本発明におけるアディポネクチン産生促進剤は、例えば医薬品又は飲食品等での提供が可能となる。本発明によるアディポネクチン産生促進剤、医薬品および飲食品は、安全性に優れ、血中のアディポネクチン濃度を顕著に上昇させうるものである。このため、肥満、動脈硬化、脂肪肝、糖尿病などの各種疾病の予防又は改善に極めて有用であるとともに、低アディポネクチン血症といったアディポネクチンの分泌減少を原因とした新しい概念の病態の予防又は改善にも極めて有用である。 The adiponectin production promoter in the present invention can be provided, for example, as a pharmaceutical product or a food or drink. The adiponectin production promoter, pharmaceuticals and foods and drinks according to the present invention are excellent in safety and can remarkably increase the adiponectin concentration in blood. For this reason, it is extremely useful for the prevention or improvement of various diseases such as obesity, arteriosclerosis, fatty liver, diabetes, etc., and also for the prevention or improvement of a new concept of pathology caused by decreased secretion of adiponectin such as hypoadiponectinemia. Very useful.
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