JP4469407B1 - Blood neutral fat lowering agent - Google Patents
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- JP4469407B1 JP4469407B1 JP2009154460A JP2009154460A JP4469407B1 JP 4469407 B1 JP4469407 B1 JP 4469407B1 JP 2009154460 A JP2009154460 A JP 2009154460A JP 2009154460 A JP2009154460 A JP 2009154460A JP 4469407 B1 JP4469407 B1 JP 4469407B1
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Images
Abstract
【課題】血中中性脂肪低下剤を提供する。
【解決手段】セイヨウトチノキ抽出物を有効成分とする血中中性脂肪低下剤。
【選択図】 図1Disclosed is a blood neutral fat lowering agent.
A blood neutral fat lowering agent comprising a horse chestnut extract as an active ingredient.
[Selection] Figure 1
Description
本発明は、血中中性脂肪低下剤に関する。 The present invention relates to a blood neutral fat lowering agent.
近年、食生活の向上ないし洋風化に伴って脂質の摂取量が増加し、脂肪の過剰摂取が問題となってきている。脂肪の過剰摂取は、肥満や血清脂質の上昇を引き起こし、それに伴うさまざまな合併症(例えば、循環器系疾患、特に、冠・脳血管疾患、および、乳ガン、大腸ガン等のある種のガン等の生活習慣病)の発症の危険率が高まるなど、国民の健康保持、増進の上から社会問題ともなっている。
循環器系疾患発症のリスク要因として従来から血中コレステロール濃度の上昇が挙げられているが、最近ではコレステロールとは独立した要因として、血中トリアシルグリセロール(トリグリセリド)濃度も問題視されている。脂質異常症とは、血中コレステロール濃度の上昇および/または血中中性脂肪の一種である血中トリアシルグリセロール濃度の上昇した病態である。血中のコレステロール値が上昇した場合には、高コレステロール血症(高βリポタンパク質血症)とよばれるが、これは主として低密度リポタンパク質(LDL、βリポタンパク質)の上昇であり、動脈硬化の危険率があがることがよく知られている。また、脂質を過剰に摂取すると、血中トリアシルグリセロール濃度が上昇し、高トリアシルグリセロール血症とよばれる病態となり、高血圧症や虚血性心疾患などの動脈硬化性疾患につながる危険性が高いことが指摘されている。
In recent years, with the improvement of dietary habits or westernization, the intake of lipid has increased, and excessive intake of fat has become a problem. Overdose of fat causes obesity and increased serum lipids, and various complications associated with it (for example, cardiovascular diseases, especially coronary and cerebrovascular diseases, and certain types of cancer such as breast cancer and colon cancer) It has become a social problem from the standpoint of maintaining and improving the health of the people, such as an increased risk of developing lifestyle-related diseases.
As a risk factor for the development of cardiovascular disease, an increase in blood cholesterol concentration has been conventionally cited, but recently, blood triacylglycerol (triglyceride) concentration is regarded as a problem as a factor independent of cholesterol. Dyslipidemia is a pathological condition in which blood cholesterol level is increased and / or blood triacylglycerol level, which is a kind of blood neutral fat, is increased. When the cholesterol level in the blood rises, it is called hypercholesterolemia (high β-lipoproteinemia), which is mainly an increase in low-density lipoprotein (LDL, β-lipoprotein) and arteriosclerosis. It is well known that the risk factor increases. In addition, excessive intake of lipids increases blood triacylglycerol concentration, leading to a condition called hypertriacylglycerolemia, which has a high risk of leading to arteriosclerotic diseases such as hypertension and ischemic heart disease. It has been pointed out.
セイヨウトチノキに含まれるクマリン類、特にエスクレチンあるいはエスクリンは、化粧料や抗炎症用皮膚外用剤などに配合されている。たとえば、刺激感のクレンジング化粧料(特許文献1:特開2007−161727号公報)、皮膚バリア機能を向上させる皮膚外用剤(特許文献2:特開2007−161612号公報)、抗炎症作用を有する皮膚外用剤(特許文献3:特開2006−28094号公報)、タイプ2ヘルパーT細胞型サイトカイン抑制剤(特許文献4:特開2004−75619号公報)、エラスターゼ阻害作用を有し、皮膚のハリや弾力を保持することのできる皮膚化粧料(特許文献5:特開2003−2820号公報)、退変色防止剤(特許文献6:特開2002−275467号公報)、メラニン産生抑制剤を含有する敏感肌用の美白化粧料(特許文献7:特開2000−273019号公報)が挙げられる。 Coumarins contained in horse chestnut, especially esculetin or esculin, are blended in cosmetics and anti-inflammatory skin external preparations. For example, cleansing cosmetics with irritation (Patent Document 1: Japanese Patent Application Laid-Open No. 2007-161727), skin external preparations that improve the skin barrier function (Patent Document 2: Japanese Patent Application Laid-Open No. 2007-161612), and anti-inflammatory activity External preparation for skin (Patent Document 3: Japanese Patent Application Laid-Open No. 2006-28094), Type 2 helper T cell type cytokine inhibitor (Patent Document 4: Japanese Patent Application Laid-Open No. 2004-75619), has an elastase inhibitory action, and is firm to the skin And a skin cosmetic that can retain elasticity (Patent Document 5: Japanese Patent Laid-Open No. 2003-2820), an anti-fading agent (Patent Document 6: Japanese Patent Laid-Open No. 2002-275467), and a melanin production inhibitor. Whitening cosmetics for sensitive skin (Patent Document 7: JP 2000-273019 A) can be mentioned.
本願発明者は、エスクリン/エスクレチンを含有する抗肥満剤に関する特許出願を行い(特願2009-107250号)、エスクリン/エスクレチン単体の総コレステロール低減効果を確認した。また、その明細書中にエスクリン/エスクレチンを高含有する植物素材としてセイヨウトチノキを挙げ、記載している。
本発明は、セイヨウトチノキの抽出物に、上記エスクリン/エスクレチン単体以上の血中中性脂肪低下効果を見出したものである。
The present inventor filed a patent application regarding an anti-obesity agent containing esculin / esculetin (Japanese Patent Application No. 2009-107250), and confirmed the total cholesterol reduction effect of esculin / esculetin alone. Further, in the specification, horse chestnut is cited and described as a plant material containing a high content of esculin / esculetin.
In the present invention, the extract of horse chestnut has been found to have an effect of lowering blood neutral fat more than the above-mentioned esculin / esculetin alone.
本発明は、血中中性脂肪低下剤を提供することを課題とする。 An object of the present invention is to provide a blood neutral fat lowering agent.
すなわち、本発明の主な構成は、次のとおりである。
1. セイヨウトチノキの樹皮からの抽出物を有効成分とする経口用血中中性脂肪低下剤。
2. 抽出物が水及び/又はエタノールを用いて抽出処理して得られる1.に記載された経口用血中中性脂肪低下剤。
That is, the main configuration of the present invention is as follows.
1. An oral blood neutral fat lowering agent comprising an extract from bark of horse chestnut as an active ingredient.
2. 1. Extract is obtained by extraction with water and / or ethanol Or a blood neutral fat lowering agent for oral use described in 1. above.
本発明は、高カロリーで高脂肪な食事を取っても、本発明の血中中性脂肪低下剤により血中中性脂肪の上昇を抑制することができ、冠動脈疾患の相対リスクを低減することができる。
具体的にはセイヨウトチノキ抽出物の摂取によって、血中中性脂肪を低減させることができる。セイヨウトチノキ抽出物は血中中性脂肪低下剤、医薬、食品添加剤、動物用飼料添加剤などに用いることができる。
The present invention can suppress an increase in blood triglyceride by the blood triglyceride lowering agent of the present invention even if a high-calorie, high-fat meal is taken, and reduce the relative risk of coronary artery disease. Can do.
Specifically, blood triglycerides can be reduced by ingesting horse chestnut extract. Horse chestnut extract can be used for blood neutral fat lowering agent, medicine, food additive, animal feed additive and the like.
セイヨウトチノキは、ギリシャ、ブルガリア地方の原産である。マロニエの名で知られ、並木や公園樹としてヨーロッパで重宝されている。セイヨウトチノキのサク果には一面に棘があるが、日本のトチノキの実にはない。学名はAesculus hippocastanumで、トチノキ科トチノキ属である。
薬用として利用される部位は、葉・樹皮・種子で、用途は、収斂止血・下痢止め・去痰剤として使用される。成分はエスクリン/エスクレチンを含有するクマリン配糖体が知られている。
実施例としては、樹皮をエタノールまたは熱水で抽出した抽出物を例示する。
Horse chestnut is native to the Bulgarian region of Greece. Known as the name of Maronnier, it is useful in Europe as a row of trees and park trees. There is a spine on the surface of the horse chestnut but not the fruit of the Japanese horse chestnut. The scientific name is Aesculus hippocastanum, which belongs to the genus Toxinaceae.
The parts used for medicinal purposes are leaves, bark, and seeds, and the uses are used as astringent hemostasis, anti-diarrhea, and expectorant. As a component, coumarin glycosides containing esculin / esculetin are known.
As an Example, the extract which extracted the bark with ethanol or hot water is illustrated.
本発明は、血中中性脂肪低下剤、食品添加物、食品およびペットフード、動物用医薬として利用することができる。剤型は、公知の方法により助剤とともに任意の形態に製剤化して、経口投与することができる。カプセル剤又は錠剤、顆粒剤、細粒剤、散剤、液状として投与できる。
投与量は、投与方法と、患者の年齢、病状や一般状態等によって変化し得るが、動物試験の結果より成人では体重1kg当たり通常、1日当たり有効成分として1〜1,000mgが適当である。
The present invention can be used as a blood neutral fat lowering agent, food additive, food and pet food, and veterinary medicine. The dosage form can be formulated into an arbitrary form together with an auxiliary agent by a known method and administered orally. It can be administered as a capsule or tablet, granule, fine granule, powder, or liquid.
The dose may vary depending on the administration method and the age, medical condition, general condition, etc. of the patient, but from the results of animal tests, 1 to 1,000 mg as an active ingredient per day is usually appropriate for 1 kg of body weight in adults.
本発明の血中中性脂肪低下剤は、一般食品や健康食品に配合することができ、また、食品添加物の成分とすることもできる。配合する食品は特に限定されず、例えば食パン、菓子パン、パイ、デニッシュ、ドーナツ、ケーキ等のベーカリー食品、うどん、そば、中華麺、焼きそば、パスタ等の麺類、天ぷら、コロッケ等のフライ類、カレー、シチュー、ドレッシング等のソース類、ふりかけ類、かまぼこ等の練り製品、ジュース等の飲料、スナック菓子、米菓、飴、ガム等の菓子類を挙げることができる。
ペットには、犬、猫、ハムスター、リス等の哺乳類の飼料として適している。本発明のペットフードの形態は特に限定されるものではなく、例えばドライタイプ、ウェットタイプ、セミモイストタイプ、ビスケットタイプ、ソーセージタイプ、ジャーキータイプ、粉末、顆粒、カプセルなどが挙げられる。
The blood neutral fat lowering agent of the present invention can be incorporated into general foods and health foods, and can also be used as a component of food additives. The food to be blended is not particularly limited, for example, bakery food such as bread, confectionery bread, pie, Danish, donut, cake, noodles such as udon, soba, Chinese noodles, yakisoba, pasta, fries such as tempura, croquette, curry, Examples include sauces such as stew and dressing, sprinkles, kneaded products such as kamaboko, beverages such as juice, and confectionery such as snacks, rice cakes, rice cakes, and gums.
Suitable for pets as feed for mammals such as dogs, cats, hamsters and squirrels. The form of the pet food of the present invention is not particularly limited, and examples thereof include dry type, wet type, semi-moist type, biscuit type, sausage type, jerky type, powder, granule, capsule and the like.
[C57BL/6CrSlcマウスを用いた評価]
高脂肪飼料にセイヨウトチノキ抽出物を配合してC57BL/6CrSlcマウスの血清生化学検査を行った。
[Evaluation using C57BL / 6CrSlc mice]
Serum biochemistry of C57BL / 6CrSlc mice was performed with high-fat diet mixed with horse chestnut extract.
<高脂肪飼料調製>
高脂肪飼料は通常の飼育に使用するオリエンタル酵母の粉末飼料(MF粉末飼料)をベースにさらに脂肪成分を添加し、下記に示したような成分で調製した。
<High fat feed preparation>
The high fat diet was prepared with the components shown below by further adding fat components based on oriental yeast powder feed (MF powder feed) used for normal breeding.
<実験動物>
雄性7週齢のC57BL/6CrSlc マウスを計25匹、7日間予備飼育して実験に供する。マウスは予備飼育期間および実験期間を通して室温23±5℃、相対湿度55±15%の飼育室(照明時間12時間)で飼育する。
マウスは5匹/ケージとし、普通飼料(ND)は週2回補充、高脂肪飼料(HFD)はvehicle投与群の1日消費量(2〜3g/mouse/day)と同量をすべての薬物投与群に与え、HFDは毎日補充した。飲料水は水道水を給水瓶で自由に与えた。
<Experimental animals>
A total of 25 male 7-week-old C57BL / 6CrSlc mice, preliminarily raised for 7 days, are used for the experiment. Mice are kept in a breeding room (lighting time 12 hours) at room temperature 23 ± 5 ° C. and relative humidity 55 ± 15% throughout the preliminary breeding period and experimental period.
5 mice / cage, normal diet (ND) supplemented twice a week, high-fat diet (HFD) with the same daily consumption (2-3 g / mouse / day) of the vehicle administration group as all drugs The administration group was given and HFD was replenished daily. Drinking water was given tap water freely with a water bottle.
<セイヨウトチノキ熱水抽出物の試作>
セイヨウトチノキ樹皮部の乾燥粉砕物1kgを15リットルの水に浸漬し、1時間加熱した。次いで、ろ過して残渣を再び15リットルの水で同様に処理した。上記2回の処理により得られた抽出液を、合わせて減圧下に濃縮し、濃縮液を得た。この濃縮液を減圧下で乾燥し、228gのセイヨウトチノキ熱水抽出物を得た。
<Trial manufacture of hot spring extract of horse chestnut>
1 kg of dried and ground bark of the horse chestnut was immersed in 15 liters of water and heated for 1 hour. It was then filtered and the residue treated again with 15 liters of water. The extracts obtained by the above two treatments were combined and concentrated under reduced pressure to obtain a concentrated solution. This concentrated solution was dried under reduced pressure to obtain 228 g of a hot water extract of horse chestnut.
<セイヨウトチノキ90%エタノール抽出物の試作>
セイヨウトチノキ樹皮部の乾燥粉砕物1kgを15リットルの90容量% エタノールに浸漬し、還流下で1時間加熱した。次いで、ろ過して残渣を再び15リットルの90容量% エタノールで同様に処理した。上記2回の処理により得られた抽出液を、合わせて減圧下に濃縮し、濃縮液を得た。この濃縮液を減圧下で乾燥し、180gのセイヨウトチノキ90%エタノール抽出物を得た。
なお、セイヨウトチノキ抽出物に含まれるエスクリン、エスクレチン量を測定したところ表2に示す結果を得た。これは、セイヨウトチノキ熱水抽出物50mg中に含まれるエスクリン量は約10.0mg、エスクレチン量は約0.17mgであり、セイヨウトチノキエタノール抽出物50mg中に含まれるエスクリン量は約9.4mg、エスクレチン量は約0.4mgである。
<Trial production of 90% ethanol extract of horse chestnut>
1 kg of a dry pulverized product of a horse chestnut bark was immersed in 15 liters of 90 vol% ethanol and heated under reflux for 1 hour. It was then filtered and the residue treated again with 15 liters of 90% by volume ethanol. The extracts obtained by the above two treatments were combined and concentrated under reduced pressure to obtain a concentrated solution. This concentrated solution was dried under reduced pressure to obtain 180 g of a horse chestnut 90% ethanol extract.
When the amounts of esculin and esculetin contained in the horse chestnut extract were measured, the results shown in Table 2 were obtained. This is because the amount of esculin contained in 50 mg of hot water extract of horse chestnut is about 10.0 mg, the amount of esculetin is about 0.17 mg, and the amount of esculin contained in 50 mg of horse chestnut ethanol extract is about 9.4 mg, The amount of esculetin is about 0.4 mg.
<投与する薬物>
セイヨウトチノキの熱湯抽出物(BW)、セイヨウトチノキのエタノール抽出物(EtOH)を50mg/kg、一日置きに経口投与した。それぞれの薬物は5% Cremophor(R) ELに溶解し経口投与した。また、vehicle群として薬物を含まない5% Cremophor水溶液を同様に経口投与した。
<Drugs to be administered>
A hot water extract of horse chestnut (BW) and an ethanol extract of horse chestnut (EtOH) were orally administered every other day at 50 mg / kg. Each drug was dissolved in 5% Cremophor® EL and administered orally. Further, as a vehicle group, a 5% Cremophor aqueous solution containing no drug was orally administered in the same manner.
<生化学検査>
実験開始後16週経過後のマウスに対して全血を採血し血中中性脂肪(TG)に関して検査を行った。測定は日立7180型自動分析装置を用いて測定した。
結果を図1に示す。得られた値はt-検定を行い有意確率(P値)を求めp<0.05の時は*、p<0.01の時は**、p>0.05の時はNSと表記する。
<Biochemical testing>
Whole blood was collected from mice 16 weeks after the start of the experiment and examined for blood neutral fat (TG). The measurement was performed using a Hitachi 7180 type automatic analyzer.
The results are shown in FIG. The obtained value is t-tested to obtain the significance (P value) and is expressed as * when p <0.05, ** when p <0.01, and NS when p> 0.05.
(結果)
高脂肪飼料のみを与えたマウスvehicle(HFD)に較べてセイヨウトチノキ熱水抽出物(BW)及びセイヨウトチノキエタノール抽出物(EtOH)添加高脂肪飼料投与したマウスの血中中性脂肪が抑制されていることがわかる。
本出願人に係る先願(特願2009-107250号)においては、エスクリン及びエスクレチン添加高脂肪飼料投与(ECL(HFD))したマウスに血中中性脂肪低下が認められたが、この先願にかかる提案ではエスクリン又はエスクレチンを30mg/kg投与した結果として血中中性脂肪低下が確認されている。一方前述のとおり、本発明のセイヨウトチノキ抽出物50mgにはエスクリン量は10mg、エスクレチン量は0.3mgが含まれているのであるから、先願の知見との比較において、本願発明のセイヨウトチノキ抽出物では、エスクリン量換算では1/3、エスクレチン量換算では1/100量相当において、血中中性脂肪低下作用を発揮することが確認できたのである。
本発明のセイヨウトチノキ熱水抽出物(BW)及びセイヨウトチノキエタノール抽出物(EtOH)にエスクリン/エスクレチン単体以上の血中中性脂肪低下効果があることを見出した。
よって、セイヨウトチノキ熱水抽出物(BW)及び/又はセイヨウトチノキエタノール抽出物(EtOH)の継続摂取によって、血中中性脂肪低減効果を奏することがわかる。
(result)
Compared to mouse vehicle (HFD) fed with high-fat diet alone, blood neutral fat in mice administered with high-fat diet supplemented with hot water extract of horse chestnut (BW) and ethanol extract of horse chestnut ethanol (EtOH) was suppressed. I understand that.
In a previous application (Japanese Patent Application No. 2009-107250) relating to the present applicant, a decrease in blood neutral fat was observed in mice administered with high-fat diet containing esculin and esculetin (ECL (HFD)). In this proposal, blood triglyceride reduction has been confirmed as a result of administering 30 mg / kg of esculin or esculetin. On the other hand, as described above, 50 mg of the horse chestnut extract of the present invention contains 10 mg of esculin and 0.3 mg of esculetin, so in comparison with the findings of the previous application, In the product, it was confirmed that the blood neutral fat lowering effect was exhibited at 1/3 in terms of esculin and 1/100 in terms of esculetin.
It has been found that the hot water extract of horse chestnut (BW) and the extract of horse chestnut ethanol (EtOH) of the present invention have an effect of lowering blood neutral fat more than esculin / esculetin alone.
Therefore, it can be seen that continuous intake of the horse chestnut hot water extract (BW) and / or the horse chestnut ethanol extract (EtOH) has an effect of reducing blood neutral fat.
以下に本発明のセイヨウトチノキ抽出エキスを用いた処方例を示す。
処方例1
[カプセル剤]
組成
セイヨウトチノキ抽出エキス(エタノール抽出)…100mg
ミツロウ …10mg
ぶどう種子オイル …110mg
上記成分を混合し、ゼラチンおよびグリセリンを混合したカプセル基剤中に充填し、軟カプセルを得た。
The example of prescription using the horse chestnut extract of this invention is shown below.
Formulation Example 1
[Capsule]
Composition Horse chestnut extract (ethanol extraction) ... 100mg
Beeswax 10mg
Grape seed oil… 110mg
The above ingredients were mixed and filled into a capsule base mixed with gelatin and glycerin to obtain soft capsules.
処方例2
[錠剤]
組成
セイヨウトチノキ抽出エキス(エタノール抽出)…150mg
セルロース …80mg
デンプン …20mg
ショ糖脂肪酸エステル …2mg
上記成分を混合、打錠し、錠剤を得た。
Formulation example 2
[tablet]
Composition Horse chestnut extract (ethanol extraction) ... 150mg
Cellulose… 80mg
Starch ... 20mg
Sucrose fatty acid ester 2mg
The above components were mixed and tableted to obtain tablets.
処方例3
〔飲料〕
(組 成) (配合;質量%)
果糖ブトウ糖液糖 5.00
クエン酸 10.4
L−アスコルビン酸 0.20
香料 0.02
色素 0.10
セイヨウトチノキ抽出エキス(エタノール抽出) 1.00
水 82.28
Formulation Example 3
[Beverages]
(Composition) (Composition: Mass%)
Fructose butter sugar liquid sugar 5.00
Citric acid 10.4
L-ascorbic acid 0.20
Perfume 0.02
Dye 0.10
Horse chestnut extract (ethanol extraction) 1.00
Water 82.28
Claims (2)
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS58150514A (en) * | 1982-03-03 | 1983-09-07 | Nippon Shinyaku Co Ltd | Lipid metabolism improver |
JP2005503332A (en) * | 2001-02-02 | 2005-02-03 | イェルク・ペーター・シューア | Symbiotic regenerant |
JP2007119430A (en) * | 2005-10-31 | 2007-05-17 | Ichimaru Pharcos Co Ltd | Activator of peroxisome proliferator-activated receptor |
JP2007519603A (en) * | 2003-06-27 | 2007-07-19 | インデナ エッセ ピ ア | Combinations of vascular protective substances and formulations containing them |
JP2007238468A (en) * | 2006-03-06 | 2007-09-20 | Kotobuki Seika Kk | Substance having lipase inhibition activity and food containing the same |
JP2008069134A (en) * | 2006-09-15 | 2008-03-27 | Noevir Co Ltd | Composition for slimming body |
-
2009
- 2009-06-30 JP JP2009154460A patent/JP4469407B1/en active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS58150514A (en) * | 1982-03-03 | 1983-09-07 | Nippon Shinyaku Co Ltd | Lipid metabolism improver |
JP2005503332A (en) * | 2001-02-02 | 2005-02-03 | イェルク・ペーター・シューア | Symbiotic regenerant |
JP2007519603A (en) * | 2003-06-27 | 2007-07-19 | インデナ エッセ ピ ア | Combinations of vascular protective substances and formulations containing them |
JP2007119430A (en) * | 2005-10-31 | 2007-05-17 | Ichimaru Pharcos Co Ltd | Activator of peroxisome proliferator-activated receptor |
JP2007238468A (en) * | 2006-03-06 | 2007-09-20 | Kotobuki Seika Kk | Substance having lipase inhibition activity and food containing the same |
JP2008069134A (en) * | 2006-09-15 | 2008-03-27 | Noevir Co Ltd | Composition for slimming body |
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