JP2010105976A - Neutral fat accumulation inhibitor - Google Patents
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- JP2010105976A JP2010105976A JP2008281281A JP2008281281A JP2010105976A JP 2010105976 A JP2010105976 A JP 2010105976A JP 2008281281 A JP2008281281 A JP 2008281281A JP 2008281281 A JP2008281281 A JP 2008281281A JP 2010105976 A JP2010105976 A JP 2010105976A
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Abstract
Description
本発明は、肥満予防、痩身等に有用な中性脂肪蓄積抑制剤に関する。 The present invention relates to a neutral fat accumulation inhibitor useful for obesity prevention, slimming and the like.
現代は夜食・過食などの機会が多い一方、運動不足が重なり生活様式が変化してきたことに伴ない大人だけでなく子供を含め肥満傾向にある。さらに、精神的及び身体的ストレスにより生体のホルモンバランスのくずれを引き起こし、生体内での脂肪代謝が正常に機能しないことから中性脂肪の異常代謝による蓄積を生じ、肥満になる傾向にある。中性脂肪の蓄積は体の均整を損なう容姿面の問題だけでなく、動脈硬化につながる高脂血症や高血圧症などの生活習慣病の引き金となる面も併せ持つことから、その予防及び治療が求められている。また、中性脂肪の蓄積に関しては肥満症のみならずそうでない人においても多くの人が関心を抱いている。 In modern times, there are many occasions such as late-night meals and overeatings, but not only adults but also children are tending to be obese due to lifestyle changes due to lack of exercise. Furthermore, the hormone balance of the living body is lost due to mental and physical stress, and fat metabolism in the living body does not function normally, so accumulation due to abnormal metabolism of neutral fat tends to occur and obesity tends to occur. The accumulation of triglycerides is not only a problem of appearance that impairs the balance of the body, but also has the aspect of triggering lifestyle-related diseases such as hyperlipidemia and hypertension that lead to arteriosclerosis. It has been demanded. In addition, many people are interested not only in obesity but also in the accumulation of neutral fat.
肥満の処置に対しては、食事療法や脂肪吸引などによる痩身法、脂肪燃焼促進法及び有酸素運動などが知られている。また、脂肪細胞中の脂肪を分解する方法などが知られている。ノルアドレナリンやアドレナリン、グルカゴンなどの生体内ホルモンは、脂肪分解の促進作用を有することが知られている。さらに、カフェイン、テオフィリンなどの化合物も同様に脂肪分解を促進する作用を有するとの報告もある。また、カフェインなどの脂肪分解性物質と成長因子を組み合わせて含有するもの（特許文献１）等が有効であると報告されている。しかし、ホルモンやカフェインなどは、副作用も予想され、痩身効果を期待して長期間使用することには問題がある。 For the treatment of obesity, a slimming method by diet therapy, liposuction or the like, a fat burning promotion method, and aerobic exercise are known. A method for decomposing fat in fat cells is also known. In vivo hormones such as noradrenaline, adrenaline, and glucagon are known to have an action of promoting lipolysis. Furthermore, there are reports that compounds such as caffeine and theophylline also have the effect of promoting lipolysis. In addition, it is reported that a substance containing a combination of a lipolytic substance such as caffeine and a growth factor (Patent Document 1) is effective. However, hormones and caffeine are also expected to have side effects and are problematic for long-term use with the expectation of a slimming effect.
一方、各種の生薬抽出物は様々な薬理効果及び機能的側面から各分野で研究されている。例えば、リパーゼ活性を阻害することで肥満の予防又は改善する生薬（特許文献２、３）、脂肪分解を促進する植物及び生薬抽出物（特許文献４、５）、体内に蓄積された脂肪の利用率を促進する生薬（特許文献６）、血中脂質濃度を下げる生薬抽出物（特許文献７）、前駆脂肪細胞の分化を抑制する植物抽出物（特許文献８）及び脂肪吸収を抑制する生薬抽出物（特許文献９）などが報告されている。
しかしながら、脂肪細胞への中性脂肪の蓄積を抑制することにより肥満を改善したり痩身を促進する生薬エキスについての報告はない。
従って、本発明の目的は、脂肪細胞への中性脂肪（トリグリセライド）の蓄積に対して優れた抑制効果を示し、かつ安全性の高い中性脂肪蓄積抑制剤、抗肥満剤、痩身剤を提供することにある。
However, there is no report on a herbal extract that improves obesity or promotes slimming by suppressing the accumulation of neutral fat in fat cells.
Accordingly, an object of the present invention is to provide a neutral fat accumulation inhibitor, anti-obesity agent, and slimming agent that exhibit an excellent inhibitory effect on the accumulation of neutral fat (triglyceride) in fat cells and that are highly safe. There is to do.
本発明者は、使用経験のある生薬に注目し、細胞に対する中性脂肪の蓄積性を評価する系を用いて種々検討してきたところ、全く意外にも、従来、肥満、脂肪、脂質などへの作用についての報告がない６種の生薬が、優れた中性脂肪蓄積抑制効果を有し、抗肥満剤や痩身剤として有用であることを見出し、本発明を完成した。 The present inventor has paid attention to herbal medicines that have been used, and has conducted various studies using a system for evaluating the accumulation of triglycerides to cells. The present inventors have found that six kinds of herbal medicines that have no report on action have an excellent effect of suppressing accumulation of neutral fat and are useful as an anti-obesity agent or slimming agent.
すなわち、本発明は、紫苑、小豆蒄、石菖根、前胡、桑白皮及び苦木から選ばれる生薬の抽出物を有効成分とする中性脂肪蓄積抑制剤、抗肥満剤及び痩身剤を提供するものである。 That is, the present invention provides a neutral fat accumulation inhibitor, an anti-obesity agent, and a slimming agent, comprising as an active ingredient an extract of a herbal medicine selected from purple persimmon, red bean persimmon, stone radish, pre-hum, mulberry white skin, and bitter tree. To do.
本発明の中性脂肪蓄積抑制剤を用いれば、細胞への中性脂肪の蓄積を抑制することにより、抗肥満、痩身、ひいてはメタボリックシンドロームの予防に有用である。本発明に用いる生薬は、長い使用経験を持つことから、長期間摂取可能である。 If the neutral fat accumulation inhibitor of the present invention is used, it is useful for the prevention of anti-obesity, slimming, and eventually metabolic syndrome by suppressing the accumulation of neutral fat in cells. Since the crude drug used in the present invention has a long experience of use, it can be taken for a long time.
本発明の中性脂肪蓄積抑制剤の有効成分は、紫苑、小豆蒄、石菖根、前胡、桑白皮及び苦木から選ばれる生薬の抽出物である。ここで、紫苑は、キク科の多年草であり、根の部分が用いられ去痰作用、抗結核作用、抗菌・抗ウイルス作用、利尿作用および鎮痛作用を有することが知られている。
小豆蒄は、ショウガ科Elettaria 属植物の果実で、用時には種子のみを用い芳香健医薬として知られている。
石菖根は、サトイモ科のセキショウの根茎を用いたものであり、鎮静作用・健胃作用・鎮痛作用・利尿作用・抗真菌作用などが知られている。
前胡は、セリ科 Umbelliferae の白花前胡 Ｐeucedanum praeruptorum Dunn.の根を乾燥したものであり、去痰作用・冠状動脈血流量の増加作用、このほかに鎮静作用もあることが知られている。
桑白皮は、クワ科クワの根皮であり、利尿・消炎作用、このほかに降圧作用のあることが知られている。
苦木は、ニガキ Picrasma quassioides Bennet (Simarubaceae)の樹皮を除いた木部であり、苦味健医薬として知られている。
The active ingredient of the neutral fat accumulation inhibitor of the present invention is an extract of a herbal medicine selected from purple persimmon, red bean persimmon, stone radish, front cucumber, mulberry bark, and bitter tree. Here, purple persimmon is a perennial plant belonging to the family Asteraceae, and is known to have an expectorant action, an antituberculosis action, an antibacterial / antiviral action, a diuretic action and an analgesic action using a root portion.
Azuki bean is a fruit of the genus Elettaria belonging to the ginger family, and it is known as an aromatic medicine using only seeds when used.
Ishizone root uses the rootstock of the taro family, and is known for its sedative, gastric, analgesic, diuretic and antifungal effects.
Apricot is dried from the roots of Peumdanum praeruptorum Dunn, a white flower of the celery family Umbelliferae, and is known to have an expectorant effect, an increase in coronary blood flow, and a sedative effect.
Mulberry bark is the root bark of the mulberry family mulberry, and is known to have a diuretic / anti-inflammatory action and, in addition, an antihypertensive action.
The bitter tree is a xylem excluding the bark of the oyster Picrasma quassioides Bennet (Simarubaceae), and is known as a bitter tasting medicine.
これらの生薬の抽出物としては、中性脂肪蓄積抑制効果を損なわない条件で抽出されたものであればよく、例えば水；メチルアルコール、エチルアルコールなどの低級アルコール；プロピレングリコール、１，３−ブチレングリコールなどの多価アルコール；アセトンなどのケトン類；ジエチルエーテル、ジオキサン、アセトニトリル、酢酸エチルエステルなどのエステル類；キシレン、ベンゼン、クロロホルムなどによる抽出物が挙げられる。これら溶媒は単独であるいは２種以上の混合溶媒を用いて抽出することもできる。これらのうち、水、低級アルコール又はこれらの混合溶媒により抽出したものが特に好ましい。 These herbal extracts may be those extracted under conditions that do not impair the effect of inhibiting neutral fat accumulation, such as water; lower alcohols such as methyl alcohol and ethyl alcohol; propylene glycol, 1,3-butylene. Examples thereof include polyhydric alcohols such as glycol; ketones such as acetone; esters such as diethyl ether, dioxane, acetonitrile, and ethyl acetate; extracts using xylene, benzene, chloroform, and the like. These solvents can be extracted singly or using two or more mixed solvents. Of these, those extracted with water, lower alcohols or mixed solvents thereof are particularly preferred.
また抽出方法も特に限定されず、浸漬法や向流抽出法を採用することができる。また抽出物は、濃縮物、乾燥品などをそのまま用いてもよく、さらに各種の精製法により精製して用いてもよい。 Further, the extraction method is not particularly limited, and an immersion method or a countercurrent extraction method can be employed. The extract may be a concentrate, a dried product, or the like as it is, or may be further purified by various purification methods.
後述の実施例に示すように、上記生薬の抽出物は脂肪細胞の前駆細胞である３Ｔ３−Ｌ１細胞への中性脂肪の蓄積を強く抑制する作用を有する。その作用は、他の生薬である烏薬、常実、杏仁、決明子、半夏、麻子仁に比べて極めて強力である。従って、本発明の中性脂肪蓄積抑制剤は、ヒトを含む哺乳類の抗肥満剤、痩身剤、メタボリック症候群防止剤、抗動脈硬化剤、抗高脂血症剤、皮下及び内臓脂肪貯蓄抑制剤、生活習慣病抑止剤、抗脂肪肝剤等として有用である。また、肝硬変や肝臓癌などの原因となるＣ型肝炎ウイルスは細胞内の中性脂肪を利用して増殖しており、さらに、ウイルスのコアと呼ばれる蛋白質の働きで、細胞内の中性脂肪が増加するという報告の見られることから新たな治療への応用が期待される。 As shown in Examples described later, the herbal extract has an effect of strongly suppressing the accumulation of triglyceride in 3T3-L1 cells, which are precursor cells of adipocytes. Its action is extremely strong compared with other herbal medicines such as glaze, Tsunemi, Anjin, Seiko, Hanka, Asako. Therefore, the neutral fat accumulation inhibitor of the present invention includes anti-obesity agents for mammals including humans, slimming agents, metabolic syndrome inhibitors, anti-arteriosclerotic agents, anti-hyperlipidemic agents, subcutaneous and visceral fat accumulation inhibitors, It is useful as a lifestyle-related disease inhibitor, anti-fatty liver agent, etc. Hepatitis C virus, which causes liver cirrhosis and liver cancer, is proliferated using the neutral fat in the cell. Furthermore, the protein called the core of the virus makes the intracellular neutral fat It is expected to be applied to new treatments due to reports of increasing numbers.
本発明の中性脂肪蓄積抑制剤、抗肥満剤、痩身剤（以下、中性脂肪蓄積抑制剤等という）は、経口及び外用のいずれの投与形態でも使用することができる。従って、これらの作用を目的とする医薬、医薬部外品、化粧料、機能性食品、特定保健用食品、ペットフード等として有用である。 The neutral fat accumulation inhibitor, anti-obesity agent, slimming agent (hereinafter referred to as neutral fat accumulation inhibitor, etc.) of the present invention can be used in both oral and external administration forms. Therefore, it is useful as a medicine, quasi-drug, cosmetics, functional food, food for specified health use, pet food, etc. for these functions.
本発明の中性脂肪蓄積抑制剤等の経口投与用の形態としては、錠剤、顆粒、粉末、カプセル等の固形剤、ゲル剤、液剤、シロップ剤等の液剤等が挙げられる。また外用の形態としては、クリーム、軟膏、乳液、ローション、オイル、パックなどの形態が挙げられる。 Examples of forms for oral administration of the neutral fat accumulation inhibitor and the like of the present invention include solid agents such as tablets, granules, powders and capsules, and liquid agents such as gels, solutions and syrups. Examples of the external form include creams, ointments, emulsions, lotions, oils, packs and the like.
本発明の中性脂肪蓄積抑制剤等中の前記生薬抽出物の含有量は特に制限されないが、乾燥固形分として０．００１〜１００質量％、さらに０．１〜５０質量％、特に０．１〜３０質量％が好ましい。また、前記生薬抽出物以外の他の薬効成分、例えばリパーゼ阻害剤、脂肪分解促進剤、血中脂質低下剤等を配合することもできる。 The content of the herbal extract in the neutral fat accumulation inhibitor and the like of the present invention is not particularly limited, but is 0.001 to 100% by mass, further 0.1 to 50% by mass, particularly 0.1 to 0.1% by dry solid content. -30 mass% is preferable. In addition, other medicinal ingredients other than the herbal extract, such as lipase inhibitors, lipolysis promoters, blood lipid lowering agents, and the like may be added.
次に実施例を挙げて本発明を詳細に説明する。 EXAMPLES Next, an Example is given and this invention is demonstrated in detail.
製造例
各生薬１重量部を３０％アルコール水２０重量部に一昼夜浸漬させ濾過した後、蒸発乾固する。その残渣に水２重量部を加えよく混和後、再度濾過して不溶分を除去した。
Production Example 1 part by weight of each herbal medicine is immersed in 20 parts by weight of 30% alcohol water for 24 hours, filtered, and then evaporated to dryness. After adding 2 parts by weight of water to the residue and mixing well, it was filtered again to remove insolubles.
実施例１〜１２及び比較例１
実験マウス由来の前駆脂肪細胞３Ｔ３−Ｌ１を６穴マルチプレートで１０％牛胎児血清を含むＤＭＥ培地（ダルベッコ変法イーグル培地）により３７℃で２日間培養した。その後、培地にデキサメタゾン（０．０５Ｍ）、イソブチルメチルキサンチン（０．５ｍＭ）およびインスリン（１μｇ／ｍＬ）を加え脂肪細胞へと分化させた。分化誘導処理は２日間行い、その後は生薬抽出物を含む培地で２〜３日毎に１２日間培地を交換しながら培養した。なお、培養液中の生薬抽出物濃度は０．５ｍｇ／ｍＬとした。脂肪細胞へ分化した３Ｔ３−Ｌ１細胞はＤＰＢＳ（ダルベッコ・リン酸緩衝液）で洗浄後、２５ｍＭ Ｔｒｉｓ緩衝液で溶解した。中性脂肪はクロロホルム／エタノールで抽出し、クロロホルム画分を風乾し、中性脂肪測定用サンプルとした。中性脂肪はＴＧ測定キット（和光純薬工業（株））で測定した。試験を行うにあたり、各抽出成分に細胞毒作用の無いことを確認して検討した。
Examples 1 to 12 and Comparative Example 1
Experimental mouse-derived preadipocytes 3T3-L1 were cultured in a 6-well multiplate in DME medium (Dulbecco's modified Eagle medium) containing 10% fetal bovine serum at 37 ° C. for 2 days. Thereafter, dexamethasone (0.05 M), isobutylmethylxanthine (0.5 mM) and insulin (1 μg / mL) were added to the medium to differentiate into adipocytes. Differentiation induction treatment was performed for 2 days, and thereafter, the culture was carried out in a medium containing a crude drug extract every two to three days while changing the medium for 12 days. The concentration of the herbal extract in the culture solution was 0.5 mg / mL. 3T3-L1 cells differentiated into adipocytes were washed with DPBS (Dulbecco phosphate buffer) and then lysed with 25 mM Tris buffer. Neutral fat was extracted with chloroform / ethanol, and the chloroform fraction was air-dried to obtain a sample for measuring neutral fat. Neutral fat was measured with a TG measurement kit (Wako Pure Chemical Industries, Ltd.). In conducting the test, each extracted component was confirmed to have no cytotoxic effect.
表１及び図１に示すように、対照群に比べ、紫苑を培地に添加した群ではＴＧ量が７０．６％、小豆蒄を培地に添加した群では５４．７％、石菖根を培地に添加した群では７６．１％、前胡を培地に添加した群では５２．４％、桑白皮を培地に添加した群では６９．９％、苦木を培地に添加した群では８９．３％、中性脂肪の蓄積が減少した。 As shown in Table 1 and FIG. 1, compared to the control group, the TG amount was 70.6% in the group with purple koji added to the medium, 54.7% in the group with red bean koji added to the medium, and stone root was used in the medium. 76.1% in the added group, 52.4% in the group to which cucumber was added to the medium, 69.9% in the group to which mulberry white bark was added to the medium, and 89.3 in the group to which bitter tree was added to the medium. %, Neutral fat accumulation decreased.
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