JP6220081B2 - Composition for improving, preventing or treating metabolic diseases comprising Borage extract - Google Patents
Composition for improving, preventing or treating metabolic diseases comprising Borage extract Download PDFInfo
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- JP6220081B2 JP6220081B2 JP2016553186A JP2016553186A JP6220081B2 JP 6220081 B2 JP6220081 B2 JP 6220081B2 JP 2016553186 A JP2016553186 A JP 2016553186A JP 2016553186 A JP2016553186 A JP 2016553186A JP 6220081 B2 JP6220081 B2 JP 6220081B2
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Description
本特許出願は、２０１３年１１月１２日大韓民国特許庁に提出された大韓民国特許出願第１０−２０１３−０１３６８７７号に対して優先権を主張し、前記特許出願の開示事項は本明細書に参照として含まれる。 This patent application claims priority to Korean Patent Application No. 10-2013-0136877 filed with the Korean Patent Office on November 12, 2013, and the disclosure of the patent application is incorporated herein by reference. included.
本発明は、ボリジ抽出物を含む代謝疾患の改善、予防または治療用組成物に関する。 The present invention relates to a composition for ameliorating, preventing or treating a metabolic disease comprising a Borage extract.
代謝疾患とは、慢性的な代謝障害によって発生する糖尿病、高血圧、高脂血症、肥満、冠動脈または動脈硬化症のような色々な疾患が同時に発生する疾患を指すものであり、１９８８年Ｒｅａｖｅｎ（Reaven GM,Diabetes,1988,37:1595-1607）によって初めて究明された。代謝疾患はインスリン抵抗性と高血圧、脂質異常症を特徴としており、その大半は過体重や肥満を伴っている。また、代謝疾患は心血管疾患の危険因子であり、全ての原因による死亡と関連していると報告された。２型糖尿病患者の場合、１型糖尿病とは異なって代謝疾患の有病率が高いと報告されており、２型糖尿病患者が代謝疾患を伴う時に死亡率が増加すると知られている（Bonora E,et al.Diabet Med.,2004,21:52-8;Ford ES,DiabetesCare.,2005,28:1769-78;Alexander CM,et al.Diabetes,2003,52:1210-1214）。また、２型糖尿病の大血管および微細血管合併症と高血圧、脂質異常症などの代謝疾患の構成要素との関連性に関する研究が発表されている（Mykkanen L,et al.Diabetologia.,1993,36:553-559;Haffner SM,etal.Diabetes,1992,41:715-722）。 A metabolic disease refers to a disease in which various diseases such as diabetes, hypertension, hyperlipidemia, obesity, coronary artery or arteriosclerosis occurring due to chronic metabolic disorders occur at the same time. Reaven GM, Diabetes, 1988, 37: 1595-1607). Metabolic diseases are characterized by insulin resistance, hypertension, and dyslipidemia, most of which are accompanied by overweight and obesity. Metabolic disease was also a risk factor for cardiovascular disease and was reported to be associated with death from all causes. In patients with type 2 diabetes, unlike premature diabetes, it is reported that the prevalence of metabolic diseases is high, and it is known that mortality increases when patients with type 2 diabetes are associated with metabolic diseases (Bonora E , et al. Diabet Med., 2004, 21: 52-8; Ford ES, DiabetesCare., 2005, 28: 1769-78; Alexander CM, et al. Diabetes, 2003, 52: 1210-1214). Research has also been published on the relationship between macrovascular and microvascular complications of type 2 diabetes and components of metabolic diseases such as hypertension and dyslipidemia (Mykkanen L, et al. Diabetologia., 1993, 36 : 553-559; Haffner SM, etal. Diabetes, 1992, 41: 715-722).
代謝疾患の最も深刻な問題点は、糖尿病性網膜症、腎症、神経障害、高脂血症、心血管疾患（脳卒中、狭心症、心筋梗塞症、末梢血管疾患）のような慢性合併症の発生である（Wolf SP,Br Med Bull.,1993,49:642-652）。このような慢性合併症の大半は、一旦発生した後には非可逆的な進行過程を踏むこととなり、今のところはこのような過程を完全に遮断できる方法はなく、適切な治療が並行されない場合には、深刻な症状を招いて患者が死亡に至ることとなる。従って、複合的な症状を有する代謝疾患の効果的な管理または治療のためには、正常な血糖を維持するための血糖降下効果と同時に腎症、肝障害、高脂血症などを治療する効果を有することが理想的であるが、未だにこのような治療剤は開発されず、血糖降下剤、血圧降下剤、コレステロール治療剤などを各々個別的に別途服用している。 The most serious problems with metabolic diseases are diabetic retinopathy, nephropathy, neuropathy, hyperlipidemia, chronic complications such as cardiovascular disease (stroke, angina, myocardial infarction, peripheral vascular disease) (Wolf SP, Br Med Bull., 1993, 49: 642-652). Most of these chronic complications will occur after an irreversible progression once they occur, and for now there is no way to completely block this process and appropriate treatment is not paralleled In some cases, the patient will die with serious symptoms. Therefore, for the effective management or treatment of metabolic diseases with complex symptoms, the effect of treating nephropathy, liver damage, hyperlipidemia, etc. simultaneously with the hypoglycemic effect to maintain normal blood sugar However, such a therapeutic agent has not been developed yet, and a hypoglycemic agent, a hypotensive agent, a cholesterol therapeutic agent, etc. are individually taken separately.
ボリジ（Borage officinalis）は古代ギリシャやローマ時代から好んで使用したハーブの一種であり、花や葉を酒に浸けて飲めば全ての悲しみや悩みを晴らし気分を引き立てるので「快活草（ｃｕｐｈｏｒｏｓｉｕｍ）」とも呼ばれた。特に、葉にはミネラル、カルシウム、カリウムなどが多く含まれており、利尿、鎮痛、発汗、浄化、皮膚軟化作用などに優れる。最近の研究結果によれば、ボリジの種は「ガンマリノレン酸（力）」を多く含有しており、生理前にイライラし易くなる軽躁状態、湿疹や皮膚病に効果があると報告されている。葉と花を入浴剤として利用すれば、皮膚を軟らかく清潔にすることは勿論、心身の緊張まで解いてくれるため、最近ではボリジ種子からオイルを絞り出してマッサージオイル、化粧用クリームなどとして利用している。 Borage (Borage officinalis) is a kind of herb that has been used since ancient Greece and Roman times, and soaking flowers and leaves in liquor will relieve all the sorrows and worries and enhance the mood. It was also called. In particular, the leaves are rich in minerals, calcium, potassium and the like, and are excellent in diuresis, analgesia, sweating, purification, emollient action and the like. According to recent research results, borage seeds contain a lot of “gamma linolenic acid (power)” and have been reported to be effective against hypomania, eczema and skin diseases that are predisposed to irritation before menstruation. . If you use leaves and flowers as a bath salt, it will not only soften and clean your skin, but will also release your mind and body tension, so recently squeezed oil from Borage seeds and used as massage oil, cosmetic cream, etc. Yes.
本明細書の全体にかけて多数の論文および特許文献が参照されており、その引用が表示されている。引用された論文および特許文献の開示内容は、その全体で本明細書に参照として含まれ、本発明が属する技術分野の水準および本発明の内容がより明確に説明される。 Throughout this specification, numerous papers and patent documents are referenced and their citations are displayed. The disclosures of the cited papers and patent documents are hereby incorporated by reference in their entirety to more clearly explain the level of technical field to which the present invention belongs and the contents of the present invention.
本発明者らは、肥満、糖尿、脂質異常症（dyslipidemia）、脂肪肝およびインスリン抵抗症候群（insulin resistance syndrome）のような代謝疾患（metabolicdisease）を改善、予防または治療できる天然物を開発しようと努力した。その結果、ボリジ（Borageofficinalis）抽出物を処理する場合に、脂肪細胞分化の減少効果、腹腔脂肪の減少効果および血中脂質の改善効果を究明することによって本発明を完成するに至った。 The inventors endeavor to develop natural products that can ameliorate, prevent or treat metabolic diseases such as obesity, diabetes, dyslipidemia, fatty liver and insulin resistance syndrome. did. As a result, the present invention has been completed by investigating the effect of reducing adipocyte differentiation, the effect of reducing abdominal fat and the effect of improving blood lipids when processing Borageofficinalis extract.
本発明の他の目的および利点は下記発明の詳細な説明、請求範囲および図面によってさらに明らかになる。 Other objects and advantages of the invention will become more apparent from the following detailed description of the invention, the claims and the drawings.
本発明の一態様によれば、本発明は、ボリジ（Borage officinalis）抽出物を有効成分として含む代謝疾患（metabolic disease）の改善、予防または治療用組成物を提供する。 According to one aspect of the present invention, the present invention provides a composition for improving, preventing or treating a metabolic disease comprising a Borage officinalis extract as an active ingredient.
本発明者らは、肥満、糖尿、脂質異常症、脂肪肝およびインスリン抵抗症候群のような代謝疾患を改善、予防または治療できる天然物を開発しようと努力した。その結果、ボリジ抽出物を処理する場合に、脂肪細胞分化の減少効果、腹腔脂肪の減少効果および血中脂質の改善効果を究明した。 The inventors have sought to develop natural products that can ameliorate, prevent or treat metabolic diseases such as obesity, diabetes, dyslipidemia, fatty liver and insulin resistance syndrome. As a result, when the Borage extract was processed, the reduction effect of adipocyte differentiation, the reduction effect of peritoneal fat, and the improvement effect of blood lipid were investigated.
本発明の組成物に用いられるボリジ抽出物は、ボリジに抽出溶媒を処理して得る場合、様々な抽出溶媒が用いられる。好ましくは、極性溶媒または非極性溶媒を用いることができる。極性溶媒として好適なものは、（ｉ）水、（ｉｉ）アルコール（好ましくは、メタノール、エタノール、プロパノール、ブタノール、ｎ−プロパノール、イソプロパノール、ｎ−ブタノール、１−ペンタノール、２−ブトキシエタノールまたはエチレングリコール）、（ｉｉｉ）酢酸、（ｉｖ）ＤＭＦＯ（dimethyl-formamide）および（ｖ）ＤＭＳＯ（dimethylsulfoxide）を含む。非極性溶媒として好適なものは、アセトン、アセトニトリル、エチルアセテート、メチルアセテート、フルオロアルカン、ペンタン、ヘキサン、２，２，４−トリメチルペンタン、デカン、シクロヘキサン、シクロペンタン、ジイソブチレン、１−ペンテン、１−クロロブタン、１−クロロペンタン、ｏ−キシレン、ジイソプロピルエーテル、２−クロロプロパン、トルエン、１−クロロプロパン、クロロベンゼン、ベンゼン、ジエチルエーテル、ジエチルスルフィド、クロロホルム、ジクロロメタン、１，２−ジクロロエタン、アニリン、ジエチルアミン、エーテル、四塩化炭素およびＴＨＦを含む。 When the borage extract used in the composition of the present invention is obtained by treating the borage with an extraction solvent, various extraction solvents are used. Preferably, a polar solvent or a nonpolar solvent can be used. Suitable polar solvents are (i) water, (ii) alcohol (preferably methanol, ethanol, propanol, butanol, n-propanol, isopropanol, n-butanol, 1-pentanol, 2-butoxyethanol or ethylene. Glycol), (iii) acetic acid, (iv) DMFO (dimethyl-formamide) and (v) DMSO (dimethylsulfoxide). Suitable nonpolar solvents are acetone, acetonitrile, ethyl acetate, methyl acetate, fluoroalkane, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1-pentene, 1 -Chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethyl sulfide, chloroform, dichloromethane, 1,2-dichloroethane, aniline, diethylamine, ether , Carbon tetrachloride and THF.
より好ましくは、本発明で用いられる抽出溶媒は、（ａ）水、（ｂ）炭素数１−４の無水または含水低級アルコール（メタノール、エタノール、プロパノール、ブタノールなど）、（ｃ）前記低級アルコールと水との混合溶媒、（ｄ）アセトン、（ｅ）エチルアセテート、（ｆ）クロロホルム、（ｇ）ブチルアセテート、（ｈ）１，３−ブチレングリコール、（ｉ）ヘキサンおよび（ｊ）ジエチルエーテルを含む。最も好ましくは、本発明の抽出物は、水、エタノールまたはその組み合わせをボリジに処理して得たものである。 More preferably, the extraction solvent used in the present invention comprises (a) water, (b) anhydrous or hydrous lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, propanol, butanol, etc.), (c) the lower alcohol and Mixed solvent with water, including (d) acetone, (e) ethyl acetate, (f) chloroform, (g) butyl acetate, (h) 1,3-butylene glycol, (i) hexane and (j) diethyl ether . Most preferably, the extract of the present invention is obtained by treating water, ethanol or a combination thereof in a borage.
本発明の一実現例によれば、本発明のボリジ抽出物は、水、エタノールまたはその組み合わせによって抽出したボリジ抽出物である。 According to one implementation of the present invention, the borage extract of the present invention is a borage extract extracted with water, ethanol or a combination thereof.
本明細書で用いられる用語「抽出物」は、上述したように当業界で生エキス（crude extract）として通用する意味を有するが、広義的には抽出物をさらに分画（fractionation）した分画物も含む。すなわち、ボリジ抽出物は、上述した抽出溶媒を用いて得たものだけでなく、それに精製過程をさらに適用して得たものも含む。例えば、前記抽出物を一定の分子量カットオフ値を有する限外ろ過膜を通過させて得た分画、様々なクロマトグラフィー（大きさ、電荷、疏水性または親和性による分離のために調製されたもの）による分離など、追加的に実施された様々な精製方法によって得えられた分画も本発明のボリジ抽出物に含まれる。 As used herein, the term “extract” has a meaning that is commonly used as a crude extract in the art as described above, but in a broad sense, a fraction obtained by further fractionating the extract. Including goods. That is, the Borage extract includes not only those obtained using the extraction solvent described above, but also those obtained by further applying a purification process thereto. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a certain molecular weight cut-off value, various chromatographies (prepared for separation by size, charge, hydrophobicity or affinity) Fraction obtained by various additional purification methods such as separation by the present invention are also included in the Borage extract of the present invention.
本発明で用いられるボリジ抽出物は、減圧蒸留および凍結乾燥または噴霧乾燥等のような追加的な過程によって粉末状態に調製されることができる。 The Borage extract used in the present invention can be prepared in a powder state by additional processes such as vacuum distillation and freeze-drying or spray-drying.
本明細書において、用語「有効成分として含む」とは、下記のボリジ抽出物の効能または活性を達成するのに十分な量を含むことを意味する。本発明は、天然植物材料のボリジから抽出した組成物であり、過量投与しても人体に副作用がないため、ボリジ抽出物が本発明の組成物に含まれた量的な上限は当業者が適切な範囲内で選択して実施することができる。 As used herein, the term “comprising as an active ingredient” means containing an amount sufficient to achieve the efficacy or activity of the following Borage extract. Since the present invention is a composition extracted from the borage, a natural plant material, and there is no side effect on the human body even when overdose, the upper limit of the amount that the borage extract is contained in the composition of the present invention is determined by those skilled in the art. Selection can be made within an appropriate range.
本発明のボリジ抽出物は、肥満、糖尿、脂質異常症、脂肪肝およびインスリン抵抗症候群からなる群より選択される代謝疾患を改善、予防または治療することができる。 The Borage extract of the present invention can improve, prevent or treat a metabolic disease selected from the group consisting of obesity, diabetes, dyslipidemia, fatty liver and insulin resistance syndrome.
本発明の一実現例によれば、前記脂質異常症は高脂血症である。 According to one implementation of the invention, the dyslipidemia is hyperlipidemia.
本発明の一実現例によれば、前記インスリン抵抗症候群は、インスリン抵抗性による肥満、高血圧、動脈硬化、高脂血症、高インスリン血症および非アルコール性脂肪肝からなる群より選択される１つ以上のインスリン抵抗症候群を含む。 According to one embodiment of the present invention, the insulin resistance syndrome is selected from the group consisting of insulin resistance obesity, hypertension, arteriosclerosis, hyperlipidemia, hyperinsulinemia and non-alcoholic fatty liver 1 Including one or more insulin resistance syndromes.
本発明のボリジ抽出物は脂肪細胞の分化を減少させる。本発明の一実現例によれば、前記ボリジ抽出物は、脂肪細胞の分化を１０〜６０％、１５〜５５％または２０〜５０％減少させる。 The Borage extract of the present invention reduces adipocyte differentiation. According to one implementation of the present invention, the Borage extract reduces adipocyte differentiation by 10-60%, 15-55% or 20-50%.
本発明のボリジ抽出物は、中性脂肪の生成を減少させる。本発明の一実現例によれば、前記ボリジ抽出物は中性脂肪を２０〜６０％、３０〜５０％または３５〜４５％減少させる。 The Borage extract of the present invention reduces the production of neutral fat. According to one embodiment of the invention, the Borage extract reduces neutral fat by 20-60%, 30-50% or 35-45%.
本発明のボリジ抽出物は、アディポネクチンの発現を増加させる。本発明の一実現例によれば、前記ボリジ抽出物はアディポネクチンのｍＲＮＡ発現を対照群に比べて３０〜７０％、４０〜６０％または４５〜５５％増加させる。 The Borage extract of the present invention increases the expression of adiponectin. According to one embodiment of the present invention, the Borage extract increases adiponectin mRNA expression by 30-70%, 40-60% or 45-55% compared to the control group.
本発明のボリジ抽出物は、レプチンの発現を減少させる。本発明の一実現例によれば、前記ボリジ抽出物はレプチンのｍＲＮＡ発現を対照群に比べて３０〜７０％、４０〜６０％または４５〜５５％減少させる。 The Borage extract of the present invention reduces leptin expression. According to one embodiment of the present invention, the Borage extract reduces leptin mRNA expression by 30-70%, 40-60% or 45-55% compared to the control group.
本発明のボリジ抽出物は、腹腔脂肪を減少させる。本発明の一実現例によれば、前記ボリジ抽出物は腹腔脂肪の生成を対照群に比べて３０〜７０％、４０〜６０％または４５〜５５％減少させる。 The Borage extract of the present invention reduces peritoneal fat. According to one embodiment of the present invention, the Borage extract reduces peritoneal fat production by 30-70%, 40-60% or 45-55% compared to the control group.
前記腹腔脂肪は内臓脂肪と同じ意味であり、組織（例えば、胃、肝、腸、腎臓など）の間および腹部内に位置した脂肪を意味する。腹腔脂肪は、皮膚下の皮下脂肪（subcutaneous fat）および骨格筋に位置する筋肉内脂肪（intramuscularfat）とは差がある。太股および臀部のような下半身に位置する脂肪は皮下であり、組織と一定の間隔をおかない反面、腹腔脂肪は概ね内臓および半流動性の特徴を有する。腹腔脂肪は、腸間膜（mesenteric）、精巣上体の白色脂肪組織（epididymal whiteadipose tissue；ＥＷＡＴ）および腎周囲脂肪組織（perirenal adipose tissue）の脂肪蓄積（adipose depot）で構成される。腹腔脂肪は脂肪組織と見なされる反面、皮下脂肪は脂肪組織と見なされない。 The abdominal fat is synonymous with visceral fat and means fat located between tissues (eg, stomach, liver, intestine, kidney, etc.) and in the abdomen. Peritoneal fat is different from subcutaneous fat under the skin and intramuscular fat located in skeletal muscle. Fat located in the lower body, such as the thighs and hips, is subcutaneous and does not leave a certain distance from the tissue, whereas abdominal fat has generally visceral and semi-fluid characteristics. Peritoneal fat is composed of mesenteric, epididymal white adipose tissue (EWAT) and adipose depot of perirenal adipose tissue. While peritoneal fat is considered adipose tissue, subcutaneous fat is not considered adipose tissue.
本発明のボリジ抽出物は、血中総コレステロール、血中中性脂肪、血中遊離脂肪酸および血糖を減少させる。本発明の一実現例によれば、前記ボリジ抽出物は対照群に比べて各々１０〜５０％、２０〜４０％または２５〜３５％、４５〜８５％、５５〜７５％または６０〜７０％、３０〜７０％、４０〜６０％または４５〜５５％、および１０〜６０％、１２〜５５％または１４〜５０％減少させる。 The Borage extract of the present invention reduces blood total cholesterol, blood neutral fat, blood free fatty acids and blood sugar. According to one embodiment of the present invention, the Borage extract is 10-50%, 20-40% or 25-35%, 45-85%, 55-75% or 60-70%, respectively, compared to the control group. , 30-70%, 40-60% or 45-55%, and 10-60%, 12-55% or 14-50%.
本発明のボリジ抽出物は、血圧上昇を減少させる。本発明の一実現例によれば、前記ボリジ抽出物は２〜２０％、３〜１８％または５〜１５％減少させる。 The Borage extract of the present invention reduces the rise in blood pressure. According to one implementation of the invention, the Borage extract is reduced by 2-20%, 3-18% or 5-15%.
本発明の組成物は、食品組成物、機能性食品組成物または薬剤学的組成物として提供され得る。 The composition of the present invention can be provided as a food composition, a functional food composition or a pharmaceutical composition.
本発明の組成物は食品組成物として提供され得る。本発明のボリジ抽出物を有効成分として含む肥満、糖尿、脂質異常症、脂肪肝およびインスリン抵抗症候群からなる群より選択される代謝疾患の改善、予防または治療用組成物が食品組成物として調製される場合、有効成分としてボリジ抽出物のみならず、食品製造時に通常添加される成分を含み、例えば、タンパク質、炭水化物、脂肪、栄養素、調味剤および香味剤を含む。上述した炭水化物の例としては、単糖類、例えば葡萄糖、果糖など、二糖類、例えばマルトース、スクロース、オリゴ糖など、および多糖類、例えばデキストリン、シクロデキストリン等のような通常の糖、およびキシリトール、ソルビトール、エリトリトール等の糖アルコールである。香味剤としては、天然香味剤［タウマチン、ステビア抽出物（例えば、レバウジオシドＡ、グリシルリジンなど］）、および合成香味剤（サッカリン、アスパルテーム等）を用いられる。例えば、本発明の食品組成物がドリンク剤として製造される場合には、本発明のボリジ抽出物の他にクエン酸、異性化糖、砂糖、葡萄糖、酢酸、リンゴ酸、果汁、ナツメ抽出液、ナツメ抽出液、甘草抽出液などをさらに含むことができる。 The composition of the present invention may be provided as a food composition. A composition for improving, preventing or treating a metabolic disease selected from the group consisting of obesity, diabetes, dyslipidemia, fatty liver and insulin resistance syndrome, containing the Borage extract of the present invention as an active ingredient is prepared as a food composition. In this case, not only the borage extract as an active ingredient, but also ingredients usually added at the time of food production, for example, proteins, carbohydrates, fats, nutrients, seasonings and flavoring agents are included. Examples of the carbohydrates mentioned above include monosaccharides such as sucrose and fructose, disaccharides such as maltose, sucrose, oligosaccharides, and polysaccharides such as normal sugars such as dextrin, cyclodextrin, and xylitol, sorbitol. Sugar alcohols such as erythritol. As the flavoring agent, natural flavoring agents [thaumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.)] and synthetic flavoring agents (saccharin, aspartame, etc.) are used. For example, when the food composition of the present invention is produced as a drink, in addition to the Borage extract of the present invention, citric acid, isomerized sugar, sugar, sucrose, acetic acid, malic acid, fruit juice, jujube extract, Jujube extract, licorice extract and the like can be further included.
本発明のボリジ抽出物を有効成分として含む肥満、糖尿、脂質異常症、脂肪肝およびインスリン抵抗症候群からなる群より選択される代謝疾患の改善、予防または治療用組成物は、機能性食品組成物として調製されることができる。本発明の組成物が機能性食品組成物として調製される場合、食品製造時に通常添加される成分を含み、例えば、タンパク質、炭水化物、脂肪、栄養素および調味剤を含む。例えば、ドリンク剤として製造される場合には、有効成分としてボリジ抽出物の他に、香味剤または天然炭水化物を追加成分として含むことができる。例えば、天然炭水化物は、単糖類（例えば、グルコース、フルクトース等）、二糖類（例えば、マルトース、スクロース等）、オリゴ糖、多糖類（例えば、デキストリン、シクロデキストリン等）、および糖アルコール（例えば、キシリトール、ソルビトール、エリトリトール等）を含む。香味剤としては、天然香味剤（例えば、タウマチン、ステビア抽出物等）、および合成香味剤（例えば、サッカリン、アスパルテーム等）を用いることができる。 A composition for improving, preventing or treating a metabolic disease selected from the group consisting of obesity, diabetes, dyslipidemia, fatty liver and insulin resistance syndrome, comprising the Borage extract of the present invention as an active ingredient is a functional food composition Can be prepared as When the composition of the present invention is prepared as a functional food composition, it contains ingredients that are usually added during food production, including, for example, proteins, carbohydrates, fats, nutrients and seasonings. For example, when manufactured as a drink, in addition to a borage extract as an active ingredient, a flavoring agent or a natural carbohydrate can be included as an additional ingredient. For example, natural carbohydrates include monosaccharides (eg, glucose, fructose, etc.), disaccharides (eg, maltose, sucrose, etc.), oligosaccharides, polysaccharides (eg, dextrin, cyclodextrin, etc.), and sugar alcohols (eg, xylitol). Sorbitol, erythritol, etc.). As the flavoring agent, natural flavoring agents (for example, thaumatin, stevia extract, etc.) and synthetic flavoring agents (for example, saccharin, aspartame, etc.) can be used.
本発明の組成物は薬剤学的組成物として調製され得る。 The composition of the present invention may be prepared as a pharmaceutical composition.
本発明の好ましい実現例によれば、本発明の組成物は、（ａ）上述した本発明のボリジ抽出物、および（ｂ）薬剤学的に許容される担体を含む薬剤学的組成物である。本明細書において、用語「薬剤学的な有効量」は、上述したボリジ抽出物の効能または活性を達成するのに十分な量を意味する。 According to a preferred embodiment of the present invention, the composition of the present invention is a pharmaceutical composition comprising (a) the above-mentioned Borage extract of the present invention, and (b) a pharmaceutically acceptable carrier. . As used herein, the term “pharmaceutically effective amount” means an amount sufficient to achieve the efficacy or activity of the Borage extract described above.
本発明の組成物が薬剤学的組成物として調製される場合、本発明の薬剤学的組成物は薬剤学的に許容される担体を含む。本発明の薬剤学的組成物に含まれる薬剤学的に許容される担体は、製剤時に通常用いられるものであり、ラクトース、デキストロース、スクロース、ソルビトール、マンニトール、でん粉、アカシアゴム、リン酸カルシウム、アルギネート、ゼラチン、ケイ酸カルシウム、微結晶性セルロース、ポリビニルピロリドン、セルロース、水、シロップ、メチルセルロース、メチルヒドロキシベンゾエート、プロピルヒドロキシベンゾエート、滑石、ステアリン酸マグネシウムおよびミネラルオイル等を含むが、これらに限定されるものではない。本発明の薬剤学的組成物は、前記成分の他に潤滑剤、湿潤剤、甘味剤、香味剤、乳化剤、懸濁剤、保存剤などをさらに含むことができる。好適な薬剤学的に許容される担体および製剤はRemington’s Pharmaceutical Sciences(19th ed.,1995）に詳細に記載されている。 When the composition of the present invention is prepared as a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier contained in the pharmaceutical composition of the present invention is usually used at the time of formulation, and lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin , Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc., but are not limited thereto . The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative and the like in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).
本発明の薬剤学的組成物は、経口または非経口投与ができ、好ましくは経口投与方式で適用される。 The pharmaceutical composition of the present invention can be administered orally or parenterally, and is preferably applied in an oral administration mode.
本発明の薬剤学的組成物の好適な投与量は、製剤化方法、投与方式、患者の年令、体重、性別、病状、食べ物、投与時間、投与経路、排泄速度および反応感応性のような要因によって多様に処方できる。本発明の薬剤学的組成物の一般的な投与量は、成人を基準に０．０００１〜１０００ｍｇ／ｄａｙ／ｋｇの範囲内である。 Suitable dosages of the pharmaceutical composition of the present invention include formulation method, mode of administration, patient age, weight, sex, medical condition, food, administration time, route of administration, excretion rate and response sensitivity. Various prescriptions can be made depending on factors. The general dosage of the pharmaceutical composition of the present invention is in the range of 0.0001 to 1000 mg / day / kg based on adults.
本発明の薬剤学的組成物は、当該発明が属する技術分野で通常の知識を有した者が容易に実施できる方法により、薬剤学的に許容される担体および／または賦形剤を用いて製剤化することによって、単位容量の形態で調製されるか、または多用量容器内に入れて調製され得る。この時、剤形は、オイルまたは水性媒質中の溶液、懸濁液、シロップ剤または乳化液の形態であるか、エキス剤、散剤、粉末剤、顆粒剤、錠剤またはカプセル剤の形態であってもよく、分散剤または安定化剤をさらに含むことができる。 The pharmaceutical composition of the present invention is formulated using a pharmaceutically acceptable carrier and / or excipient by a method that can be easily carried out by a person having ordinary knowledge in the technical field to which the invention belongs. Can be prepared in unit volume form or in multi-dose containers. At this time, the dosage form may be in the form of a solution, suspension, syrup or emulsion in an oil or aqueous medium, or in the form of an extract, powder, powder, granule, tablet or capsule. And may further include a dispersant or stabilizer.
本発明の他の態様によれば、本発明は、ボリジ（Borage officinalis）抽出物を有効成分として含む組成物を対象（subject）に投与するステップを含む代謝疾患（metabolic diseases）の改善、予防または治療方法を提供する。 According to another aspect of the present invention, the present invention relates to the improvement, prevention or prevention of metabolic diseases comprising the step of administering to a subject a composition comprising Borage officinalis extract as an active ingredient. A method of treatment is provided.
本発明の代謝疾患の改善、予防または治療方法は、上述した組成物を用いて実施するので、この両者間の共通した内容は本明細書の過度な複雑性を避けるためにその記載を省略する。 Since the method for improving, preventing or treating a metabolic disease of the present invention is carried out using the above-described composition, the description common to both is omitted in order to avoid excessive complexity of the present specification. .
本発明の特徴および利点を要約すれば次の通りである。 The features and advantages of the present invention are summarized as follows.
（ａ）本発明は、ボリジ（Borage officinalis）抽出物を有効成分として含む肥満、糖尿、脂質異常症（dyslipidemia）、脂肪肝およびインスリン抵抗症候群（insulinresistance syndrome）からなる群より選択される代謝疾患（metabolic disease）の改善、予防または治療用組成物を提供する。 (A) The present invention relates to a metabolic disease selected from the group consisting of obesity, diabetes, dyslipidemia, fatty liver and insulin resistance syndrome, which contains a Borage officinalis extract as an active ingredient ( A composition for improving, preventing or treating metabolic disease is provided.
（ｂ）本発明の組成物は、優れた脂肪細胞分化の抑制効果、腹腔脂肪の減少効果および血中脂質の改善効果を示す。 (B) The composition of the present invention exhibits an excellent inhibitory effect on adipocyte differentiation, a decrease in peritoneal fat, and an improvement in blood lipids.
以下、実施例によって本発明をより詳細に説明する。これらの実施例は単に本発明をより具体的に説明するためのものであって、本発明の要旨に応じて本発明の範囲がこれらの実施例によって制限されないことは当業界で通常の知識を有した者に明らかである。 Hereinafter, the present invention will be described in more detail with reference to examples. These examples are merely for explaining the present invention more specifically, and it is common knowledge in the art that the scope of the present invention is not limited by these examples according to the gist of the present invention. It is clear to those who have.
（実施例）
［実施例１：ボリジ抽出物の調製］
ボリジの葉、花、種を混合して粉砕した後、１０倍体積量の精製水を混合し、これらの混合溶媒から８０℃の抽出温度で６時間５回繰り返して熱水抽出した。本抽出物をろ過して真空濃縮した後、１：２でボリジとデキストリンを混合した後に噴霧乾燥してボリジ抽出物を得た。
(Example)
[Example 1: Preparation of Borage extract]
After borage leaves, flowers, and seeds were mixed and pulverized, 10 volumes of purified water were mixed, and hot water extraction was performed repeatedly from these mixed solvents at an extraction temperature of 80 ° C. for 6 hours 5 times. The extract was filtered and concentrated in vacuo, mixed with borage and dextrin at 1: 2, and then spray-dried to obtain a borage extract.
［実施例２：ボリジ抽出物の活性分析］
本発明の組成物の脂肪細胞分化の抑制および細胞内の肥満関連脂質、リポタンパク質およびホルモンの測定による内臓脂肪の減少効果を確認した。
[Example 2: Activity analysis of Borage extract]
The composition of the present invention was confirmed to inhibit visceral fat by inhibiting adipocyte differentiation and measuring intracellular obesity-related lipids, lipoproteins and hormones.
＜前脂肪細胞３Ｔ３−Ｌ１細胞分化の抑制効果＞
前脂肪細胞（preadipocyte）である３Ｔ３−Ｌ１細胞は、脂肪細胞の代謝過程を研究するのに広く用いられており、本発明においても、細胞の培養過程で組成物を処理した後、細胞の分化が少ないほど抗肥満効果が大きいことを示した。３Ｔ３−Ｌ１細胞を、培養液を用いて５％で二酸化炭素が供給される培養器にて３７℃で培養した。細胞培養液としては、１０％ ＦＢＳ（fetal bovine serum）と抗生物質（antibiotics）が含まれたDulbecco’s Modified Eagle’s Media（ＤＭＥＭ）を用いた。２〜３日の間隔で培養された細胞表面をリン酸緩衝生理食塩水（phosphate buffered saline、ＰＢＳ）で洗浄した後、０．５％トリプシン（trypsin）を入れて処理し、細胞を脱着させて継代培養した。細胞は、分化誘導物質のインスリン（５μｇ／ｍ）、デキサメタゾン（dexamethasone；ＤＥＸ、０．２５μΜ）およびＭＴＸ（l-methyl-3-methylxanthine、０．５ｍΜ）が含まれた分化誘導培養液に交換して１〜３日間培養し、脂肪細胞に分化を誘導した。培養３日後、インスリンのみ含有する培地で２〜３日間培養した後、インスリンを除去した培養液に取り替えた。中性脂肪に流入される葡萄糖測定実験や葡萄糖酸化実験時には１０〜１２日目に低濃度（５ｍＭ）葡萄糖を含有した培養液で培養し、分化誘導後にボリジ抽出物を処理した。処理された細胞は、２４ｈｒ、４８ｈｒおよび７２ｈｒ後に９６ウェルについている細胞を、ＭＴＴ分析方法を利用して細胞数を測定した。次に、ボリジ抽出物の処理後に１０日間分化させた３Ｔ３−Ｌ１細胞から中性脂肪（triacylglycerol）、アディポネクチン（adiponectin）およびレプチン（leptin）の量を各々測定した。
<Inhibition effect of preadipocyte 3T3-L1 cell differentiation>
3T3-L1 cells, which are preadipocytes, are widely used to study the metabolic processes of fat cells. In the present invention, cell differentiation is performed after the composition is treated in the cell culture process. The smaller the amount, the greater the anti-obesity effect. 3T3-L1 cells were cultured at 37 ° C. in an incubator supplied with carbon dioxide at 5% using a culture solution. As the cell culture solution, Dulbecco's Modified Eagle's Media (DMEM) containing 10% FBS (fetal bovine serum) and antibiotics (antibiotics) was used. The cell surface cultured at intervals of 2 to 3 days is washed with phosphate buffered saline (PBS), treated with 0.5% trypsin to desorb the cells. Subcultured. The cells were replaced with a differentiation-inducing culture medium containing the differentiation-inducing substances insulin (5 μg / m), dexamethasone (DEX, 0.25 μm) and MTX (l-methyl-3-methylxanthine, 0.5 mm). And cultured for 1-3 days to induce differentiation into adipocytes. After 3 days of culture, the cells were cultured in a medium containing only insulin for 2 to 3 days, and then replaced with a culture solution from which insulin was removed. At the time of sucrose measurement experiment and sucrose oxidation experiment flowing into neutral fat, culture was carried out on the 10th to 12th day in a culture solution containing a low concentration (5 mM) sucrose, and the borage extract was treated after differentiation induction. As for the treated cells, the number of cells in 96 wells after 24 hr, 48 hr and 72 hr was measured using the MTT analysis method. Next, the amounts of triacylglycerol, adiponectin, and leptin were measured from 3T3-L1 cells differentiated for 10 days after treatment of the Borage extract.
その結果は平均と標準偏差で示し、有意性の検証のために、統計処理はStudent’s t-testを利用し、ｐ＜０．０５の時に有意であると見なして表示した。その結果を図１〜図４に示す。 The results are shown as mean and standard deviation, and for the purpose of verifying significance, statistical processing was performed using Student's t-test and considered to be significant when p <0.05. The results are shown in FIGS.
測定の結果、図１から確認できるように、ボリジ抽出物を処理した場合、２４ｈｒ、４８ｈｒおよび７２ｈｒに対照群に比べて各々約２１％、３５％および４２％細胞数が対照群と比較して統計的に有意なレベルに減少した。 As a result of the measurement, as can be confirmed from FIG. 1, when the borage extract was treated, the cell numbers were about 21%, 35% and 42% respectively compared with the control group at 24 hr, 48 hr and 72 hr as compared with the control group. It decreased to a statistically significant level.
本抽出物の処理による中性脂肪の変化は、図２から確認できるように、ボリジ抽出物を４８時間処理した場合、対照群に比べて脂肪細胞内の中性脂肪の量が約３８％程度の有意な減少を示した。また、本抽出物を処理した後にアディポネクチンのｍＲＮＡ発現量を比較した結果、図３に示すように、アディポネクチンのｍＲＮＡ量において、ボリジ抽出物を４８時間処理した場合、対照群に比べて約１．５１倍程度のｍＲＮＡ発現量の増加を確認した。 As can be confirmed from FIG. 2, the change in neutral fat due to the treatment of this extract is about 38% of the amount of triglyceride in the fat cells when the Borage extract is treated for 48 hours compared to the control group. Showed a significant decrease. Moreover, as a result of comparing the mRNA expression level of adiponectin after this extract was treated, as shown in FIG. 3, when the borage extract was treated for 48 hours with the amount of adiponectin mRNA, it was about 1. An increase in mRNA expression level of about 51 times was confirmed.
本抽出物を４８時間処理した後にレプチンのｍＲＮＡ発現量を比較した結果においては、図４から確認できるように、レプチンｍＲＮＡの量において、ボリジ抽出物を処理した場合、対照群に比べて約０．４９倍の減少効果を確認した。 In the result of comparing the leptin mRNA expression level after this extract was treated for 48 hours, as can be confirmed from FIG. 4, when the borage extract was treated with the leptin mRNA amount, it was about 0 as compared with the control group. A reduction effect of .49 times was confirmed.
［実施例３：ボリジ抽出物の内臓肥満の減少効果の確認］
Ｃ５７ＢＬ／６Ｊマウスを対象に本発明の組成物を摂取するようにし、摂取前後の内臓脂肪の減少効果を確認して内臓脂肪の減少効果を確認した。
[Example 3: Confirmation of visceral obesity reduction effect of Borage extract]
C57BL / 6J mice were ingested with the composition of the present invention, and the visceral fat reducing effect before and after the ingestion was confirmed to confirm the visceral fat reducing effect.
Ｃ５７ＢＬ／６Ｊマウス３０匹（雌、１０週齢）に高脂肪／高糖分の食品（Oriental Yeast社製）を任意に８週間与えて食餌性肥満に誘導した。その後、マウスを１５匹ずつ２群に分け、正常食品（Oriental Yeast社製）を基本食として使い、非処理群（対照群）および調製済ボリジ抽出物で補充食餌を供給した群をもって研究を行った。２群の両方とも、マウスが４週間自由に食べるようにし、４週間後、一晩絶食させた後、エーテルロムプン（Rompun）／ケタミン麻酔下で開腹して腹部大動脈から放血させてマウスを犠牲にした。次に、子宮周辺の脂肪および腎臓周辺の脂肪を摘出して測量した。この２部分の脂肪重量を合わせて腹腔内の脂肪量として記録し、その結果を表１に示す。 Thirty C57BL / 6J mice (female, 10 weeks old) were arbitrarily given high fat / high sugar food (Oriental Yeast) for 8 weeks to induce dietary obesity. The mice were then divided into two groups of 15 mice, using normal food (Oriental Yeast) as the basic diet, and the non-treated group (control group) and the group supplemented with prepared borage extract. It was. In both groups, mice were allowed to eat freely for 4 weeks, then fasted overnight after 4 weeks, then opened under ether anesthesia (Rompun) / ketamine anesthesia and exsanguinated from the abdominal aorta to sacrifice the mice. I made it. Next, fat around the uterus and fat around the kidney were excised and measured. The fat weights of these two parts were combined and recorded as the amount of fat in the abdominal cavity, and the results are shown in Table 1.
その結果によれば、ボリジ抽出物を１ケ月間持続的に摂取したマウスから、全体的な体重の減少だけでなく腹腔内脂肪量が著しく減少したことを確認することができた。従って、高脂肪／高糖分食品の摂取によって蓄積された内臓脂肪がボリジ抽出物を含有する食品の摂取によって減少することが分かった。 According to the results, it was confirmed that not only overall weight loss but also intraperitoneal fat mass was significantly reduced from mice that had been continuously ingesting Borage extract for 1 month. Thus, it has been found that visceral fat accumulated by ingestion of high fat / high sugar content food is reduced by ingestion of food containing Borage extract.
［実施例４：ボリジ抽出物の糖尿病予防効果の確認］
遺伝性肥満を示し、２型糖尿病が進行される動物モデルであるＫＫ−Ａｙマウスを利用してボリジ抽出物の糖尿病予防効果と脂質代謝の改善効能を確認した。
[Example 4: Confirmation of diabetes prevention effect of Borage extract]
Using KK-Ay mice, which are hereditary obesity and an animal model for progression of type 2 diabetes, the effectiveness of Borage extract to prevent diabetes and improve lipid metabolism was confirmed.
糖尿病マウス（雌、８週齢）を８匹ずつ２群に分け、正常食品を基本食餌として使い、対照群（非処理群）とボリジ抽出物処理群を作った。２群の両方とも、糖尿病マウスは４週間自由に食べるようにした。ボリジ抽出物は最終濃度０．３％で正常食品に添加して研究に使った。 Diabetic mice (female, 8 weeks old) were divided into 2 groups of 8 animals, and normal food was used as a basic diet to create a control group (non-treated group) and a borage extract-treated group. In both groups, diabetic mice were allowed to eat freely for 4 weeks. Borage extract was added to normal food at a final concentration of 0.3% and used for research.
給食期間の間、マウスの体重とマウスの尾静脈から少量の血液を毎週採取し、簡易血糖試験機器を利用して血糖を測定して表２に示す。 During the feeding period, a small amount of blood is collected weekly from the mouse's body weight and the tail vein of the mouse, and the blood glucose is measured using a simple blood glucose test device and shown in Table 2.
給食期間の終了後、マウスは一晩絶食させた後、ロムプン／ケタミン麻酔下で開腹して腹部大動脈から採血し、肝を摘出して測量した。また、この血液から血清中総コレステロール（Total-Cholesterol；Ｔ−ＣＨ０）、トリグリセリド（Triglyceride；ＴＧ）、遊離脂肪酸（Non-esterified Fatty Acid；ＮＥＦＡ）、ＧＯＴ（GlutamicOxaloacetic Transaminase）、ＧＰＴ（Glutamic PyruvateTransaminase）、ＬＡＰ（Liver Activator Protein）、コリンエステラーゼ（Cholinesterase；ＣｈｏＥ）、総タンパク質（ＴＰ−Ｓ）およびアルブミン（ＡＬＢ−Ｓ）を、韓国中央大学病院の臨床病理学科に依頼して分析した。 After the end of the feeding period, the mice were fasted overnight, then laparotomized under lompun / ketamine anesthesia, blood was collected from the abdominal aorta, and the liver was removed and weighed. In addition, serum total cholesterol (T-CH0), triglyceride (TG), free fatty acid (Non-esterified Fatty Acid; NEFA), GOT (Glutamic Oxaloacetic Transaminase), GPT (Glutamic Pyruvate Transaminase), LAP (Liver Activator Protein), cholinesterase (Cholinesterase; ChoE), total protein (TP-S) and albumin (ALB-S) were analyzed by commissioning the Department of Clinical Pathology at the Central University Hospital, Korea.
表２は、マウスの４週間の体重変化を確認した結果である。対照群に比べてボリジ抽出物を処理した実験群の場合、マウスの平均体重は大きく増加することなく、ボリジ抽出物の摂取３週後から４ｇ以上の顕著な減少が確認された。血糖を示すデータでは、ボリジ抽出物の摂取を始めて２週後から対照群に比べて顕著な血糖の減少を示し始めた。これは、時間が経つにつれ４週目には、ボリジ抽出物を４週間摂取した時に対照群に比べて約２００ｍｇ／ｄ以上の血糖減少効果を示した。これは、抽出物が血糖上昇を効果的に阻害するということを意味する。 Table 2 shows the results of confirming changes in the body weight of mice for 4 weeks. In the experimental group treated with the borage extract compared to the control group, the average body weight of the mice was not significantly increased, and a marked decrease of 4 g or more was confirmed from 3 weeks after the intake of the borage extract. In the data showing blood glucose, it started to show a significant decrease in blood glucose compared to the control group 2 weeks after ingestion of Borage extract. This showed a blood glucose reduction effect of about 200 mg / d or more compared to the control group when the Borage extract was ingested for 4 weeks at 4 weeks as time passed. This means that the extract effectively inhibits the increase in blood sugar.
表３は、肝重量および血液試験データを示す結果である。結果によれば、先ず、肝重量、ＧＯＴおよびＧＰＴなど毒性と関連して、対照群とボリジ抽出物を摂取した群を比較すると統計的な差を示さなかった。これは、ボリジ抽出物が肝毒性を全く有しないということを示す結果である。一方、ボリジ抽出物を摂取した糖尿病マウスにおいて、Ｔ−ＣＨＯ、ＴＧおよびＮＥＦＡの全てにおいて、対照群に比べて各々約２９％、６５％、４９％の統計学的に明らかな減少を確認した。これは、ボリジ抽出物が、脂質代謝の改善作用によって高脂質血症を減少できるということを意味する。 Table 3 shows the results showing liver weight and blood test data. According to the results, first, there was no statistical difference between the control group and the group ingesting the Borage extract in relation to toxicity such as liver weight, GOT and GPT. This is a result showing that the Borage extract has no hepatotoxicity. On the other hand, in diabetic mice ingesting Borage extract, all T-CHO, TG and NEFA showed statistically clear decreases of about 29%, 65% and 49%, respectively, compared with the control group. This means that Borage extract can reduce hyperlipidemia by improving lipid metabolism.
前記結果から、ボリジ抽出物は血糖上昇の阻害と体重減少だけでなく脂質代謝の改善作用を全て有していることを示す。 From the above results, it is shown that the Borage extract has all the effects of improving lipid metabolism as well as inhibiting the increase in blood sugar and reducing body weight.
［実施例５：ボリジ抽出物の高血圧の予防効果］
老化により高血圧が誘発される高血圧動物モデルである自発性高血圧ラット（SpontaneouslyHypertensive Rat；ＳＨＲ）を使い、ボリジ抽出物の抗高血圧効能を確認した。
[Example 5: Anti-hypertensive effect of Borage extract]
Spontaneously Hypertensive Rat (SHR), a hypertensive animal model in which hypertension is induced by aging, was used to confirm the antihypertensive efficacy of Borage extract.
ＳＨＲ（雄、６週齢）を各群当たり１０匹ずつ２群に分け、正常な基本食餌を摂取する対照群と、ボリジ抽出物を含有した食品を摂取する群とに分けて実験を行った。高血圧を誘発するために、対照群は３ｍ／ｋｇ／日のプロピレングリコールを処理し、ボリジ抽出物群は３０ｍｇ／３ｍ／ｋｇ／日の投薬量でプロピレングリコールにボリジ抽出物を混合して摂取させた。いずれも４週間血圧低下効能を経口投与により確認した。その他の食事摂取と水は自由に摂取するようにした。 SHR (male, 6 weeks old) was divided into 2 groups of 10 animals per group, and the experiment was conducted by dividing the group into a control group ingesting a normal basic diet and a group ingesting a food containing borage extract. . To induce hypertension, the control group was treated with 3 m / kg / day of propylene glycol, and the borage extract group was fed with the borage extract mixed with propylene glycol at a dosage of 30 mg / 3 m / kg / day. It was. In any case, the blood pressure lowering effect was confirmed by oral administration for 4 weeks. Other dietary intake and water were freely available.
処理開始日の直前日および処理後７日、１４日、２１日および２８日目に非観血式自動血圧測定装置を用いて尾動脈で血圧を測定した。血圧の測定は、各試料の投与前に行った。血圧データを表４に示す。投与開始前、血圧は１１５ｍｍＨｇで、各群はいずれも正常数値に該当した。対照群の場合、処理後７日目に血圧が上昇し始め高血圧が現れ始めた。しかし、ボリジ抽出物を処理した場合、対照群とは異なって血圧上昇を抑制するのが観察され、１４日、２１日および２８日目には対照群と顕著な差を示し始め、投与後２８日目には約１２％程度の血圧低下が観察された。 Blood pressure was measured at the tail artery using a non-invasive automatic blood pressure measuring device on the day immediately before the treatment start date and on the 7th, 14th, 21st and 28th days after the treatment. Blood pressure was measured before administration of each sample. Blood pressure data is shown in Table 4. Before the start of administration, the blood pressure was 115 mmHg, and all groups corresponded to normal values. In the case of the control group, blood pressure began to increase on the seventh day after treatment, and hypertension began to appear. However, when the Borage extract was treated, it was observed to suppress the increase in blood pressure, unlike the control group, and began to show a significant difference from the control group on days 14, 21, and 28, and 28 A blood pressure drop of about 12% was observed on the day.
［実施例６：人体試験を通じた体重調節および肥満改善効能］
男女に本発明の組成物を摂取するようにし、摂取前後の体重変化および体脂肪測定を通じて体重調節および肥満改善効果を確認した。
[Example 6: Effect of body weight adjustment and obesity improvement through human body test]
Men and women were allowed to ingest the composition of the present invention, and the effects of weight control and obesity improvement were confirmed through changes in body weight and body fat measurements before and after the ingestion.
＜研究対象および期間＞
本検査に同意した満１９才以上６０才未満の男女５０名（男性２２名、女性２８名）を、偽薬を摂取した対照群（ｐｌａｃｅｂｏ）と本抽出物の混合物（８：２混合比）を摂取した実験群に各２５名ずつ任意に分類し、４週間偽薬または実験薬を１日４００ｍｇずつ摂取するようにした。被験者としては、体格指数（Body-Mass Index；ＢＭＩ）が２３以上の人またはウエスト径が男性９０ｃｍ、女性８０ｃｍ以上の人を選定した。摂取前と後に身長、体重、体格指数、ウエスト径、血圧、脈拍、身体組成（体脂肪率および除脂肪量−インピーダンス法）および血液検査によってＨＤＬ−コレステロール、中性脂肪および総コレステロール等を測定し、ボリジ組成物の摂取による代謝性疾患危険因子症候群の予防および改善効能評価を実施した。
<Research subjects and period>
Fifty men and women (22 men, 28 women) who were between 19 and 60 years old who agreed to the test, and a mixture of the control group (placebo) who took placebo and this extract (8: 2 mixture ratio) Each group was randomly classified into 25 ingested experimental groups, and 400 mg of placebo or experimental drug was ingested daily for 4 weeks. As subjects, a person with a body-mass index (BMI) of 23 or more or a person with a waist diameter of 90 cm male and female 80 cm or more was selected. HDL-cholesterol, triglycerides, total cholesterol, etc. are measured before and after ingestion by height, weight, body mass index, waist diameter, blood pressure, pulse, body composition (body fat percentage and lean mass-impedance method) and blood tests. In addition, prevention and improvement of metabolic risk factor syndrome by ingestion of Borage composition was evaluated.
＜体格指数（Body-Mass Index）＞
本発明のボリジ抽出物摂取群と偽薬群（Ｐｌａｃｅｂｏ）のＢＭＩ（体格指数）結果は表４に示し、結果値は平均と標準偏差とで示し、統計処理はStudent’s t-testを利用し、ｐ＜０．０５の時に有意であると見なして表示した。
<Body-Mass Index>
The BMI (physique index) results of the Borage extract intake group and the placebo group (Placebo) of the present invention are shown in Table 4, the result values are shown as the mean and standard deviation, the statistical processing uses Student's t-test, p It was considered to be significant when <0.05.
試験の結果、対照群のＢＭＩは摂取前後に大きな差はない反面、本組成物摂取群は摂取前に比べてＢＭＩが約２．４ｋｇ／ｍ２として有意な減少を示した。これにより、本発明の組成物が肥満あるいは過体重を調節あるいは改善できることが体格指数の減少によって示された。 As a result of the test, the BMI of the control group was not significantly different before and after ingestion, but the BMI was about 2.4 kg / m 2 in the composition ingestion group and showed a significant decrease compared to that before ingestion. This showed that the composition of the present invention can control or improve obesity or overweight by reducing the body mass index.
＜ウエスト径＞
本発明のボリジ抽出物摂取群と偽薬群（Ｐｌａｃｅｂｏ）のウエスト径を図５に示し、結果値は平均と標準偏差とで示し、統計処理はStudent’s t-testを利用し、p<0.05時に有意であると見なして表示した。
<Waist diameter>
The waist diameter of the Borage extract intake group and placebo group (Placebo) of the present invention is shown in FIG. 5, the result values are shown as the mean and standard deviation, statistical processing uses Student's t-test, and is significant when p <0.05 Displayed as if it were.
試験の結果、対照群のウエスト径は摂取前／後に大きな差はない反面、ボリジ抽出物摂取群は、摂取前に比べてウエスト径が約３．９８ｃｍほど有意な減少が観察された。これにより、本発明の組成物が腹部脂肪の増加を予防し改善できることがウエスト径の減少によって示された。 As a result of the test, the waist diameter of the control group was not significantly different before / after ingestion, but in the borage extract ingestion group, a significant decrease in the waist diameter of about 3.98 cm was observed compared with before ingestion. Thereby, it was shown by the reduction | decrease in a waist diameter that the composition of this invention can prevent and improve the increase in abdominal fat.
以上、本発明の特定部分を詳細に記述したが、当業界の通常の知識を有する者にとって、このような具体的な記述は単に好ましい実現例に過ぎず、これに本発明の範囲が制限されるものではないことは明らかである。よって、本発明の実質的な範囲は添付された請求項とその等価物によって定義されると言える。 Although specific portions of the present invention have been described in detail above, such specific descriptions are merely preferred implementations for those having ordinary skill in the art, and the scope of the present invention is limited thereto. Obviously it is not. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.
Claims (2)
前記ボリジ抽出物は、ボリジの葉、花および種の混合物の水抽出物であり、
前記代謝疾患は、肥満または糖尿である、組成物。 A composition for improving, preventing or treating metabolic diseases comprising an extract of Borage officinalis as an active ingredient ,
The borage extract is a water extract of a mixture of borage leaves, flowers and seeds;
The composition wherein the metabolic disease is obesity or diabetes .
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| KR1020130136877A KR101620077B1 (en) | 2013-11-12 | 2013-11-12 | Composition for Improving, Preventing or Treating Metabolic Diseases comprising Extracts from Borage officinalis |
| PCT/KR2014/010132 WO2015072674A1 (en) | 2013-11-12 | 2014-10-27 | Composition containing a borage officinalis extract for alleviating, preventing, or treating metabolic diseases |
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| US10111822B2 (en) | 2012-12-27 | 2018-10-30 | Hayashibara Co., Ltd. | External dermal composition for anti-ageing and method for producing the same |
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| CN108432924A (en) * | 2018-06-08 | 2018-08-24 | 贵州玉屏展鸿茶叶有限公司 | A kind of health protection tea of prevention diabetes |
| US10426806B1 (en) * | 2018-06-13 | 2019-10-01 | Muhammad Iqbal Choudhary | Anti-obesity effect of Borago officinalis linn. extracts to prevent and treat metabolic disorders |
| KR102193317B1 (en) * | 2019-03-12 | 2020-12-22 | 주식회사 엔에스웰니스 | Composition for obesity treatment and improvement |
| KR102238430B1 (en) * | 2019-05-29 | 2021-04-09 | 한국식품연구원 | A composition for improving, preventing and treating obesity and metabolic disease comprising polysaccharide fraction isolated from barley leaf |
| KR102754479B1 (en) | 2020-09-18 | 2025-01-21 | 서울대학교산학협력단 | Pharmaceutical composition for preventing or treating metabolic disease containing dimethylchalcone |
| WO2022060169A1 (en) | 2020-09-18 | 2022-03-24 | 서울대학교 산학협력단 | Composition comprising dimethylchalcone derivative for prevention or treatment of metabolic disease |
| KR20230135001A (en) | 2022-03-15 | 2023-09-22 | 중앙대학교 산학협력단 | Novel dimethylchalcone derivatives |
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| JPH11322628A (en) * | 1998-05-12 | 1999-11-24 | Fukiya Tadashi | External preparation for skin |
| KR20040052904A (en) * | 2004-05-13 | 2004-06-23 | 약초나라(주) | Products and herbal extract composition effective on the lowering for blood cholesterol and triglycerides |
| CN101978949A (en) * | 2010-11-16 | 2011-02-23 | 王京南 | Gamma-linolenate fat emulsion intravenous injection and preparation method thereof |
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