JP2007084503A - Composition containing ingredient originated from grain as active ingredient and having neovascularization inhibitory action - Google Patents
Composition containing ingredient originated from grain as active ingredient and having neovascularization inhibitory action Download PDFInfo
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- JP2007084503A JP2007084503A JP2005277652A JP2005277652A JP2007084503A JP 2007084503 A JP2007084503 A JP 2007084503A JP 2005277652 A JP2005277652 A JP 2005277652A JP 2005277652 A JP2005277652 A JP 2005277652A JP 2007084503 A JP2007084503 A JP 2007084503A
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- barley
- angiogenesis
- food
- inhibiting angiogenesis
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Abstract
Description
本発明は、穀類由来の成分を有効成分とする血管新生阻害の作用を有する組成物に関するものである。さらに詳しくは、本発明は大麦に含まれる物質、好ましくは大麦玄麦エチルアルコール抽出画分、または大麦玄麦アルカリ抽出画分を有効成分とする血管新生を阻害すべき疾患を治療または予防するための組成物、好ましくは食品素材、飲食品、飼料などの形態の組成物に関するものである。 The present invention relates to a composition having an angiogenesis-inhibiting action containing a cereal-derived ingredient as an active ingredient. More specifically, the present invention relates to a composition for treating or preventing a disease that should inhibit angiogenesis, which comprises a substance contained in barley, preferably a barley brown wheat ethyl alcohol extract fraction, or a barley brown wheat alkali extract fraction as an active ingredient. Product, preferably a composition in the form of food material, food and drink, feed and the like.
ガンは、１９８１年以来、わが国の死因のトップを占める疾患であり、３大死因の中でも、ガンだけが一貫して増加し、死亡数は増え続けている。厚生労働省の人口動態統計によると、２００１年の全死亡者数９７万３３１人のうち、３０万６５８人がガンが原因で死亡しており、実に３人に1人がガンで死亡していることとなる。このような疾患に対して、現在病院で主に施されているのは薬物、化学、物理などの各療法により、ガン細胞を直接攻撃するという対症療法であるが、この方法では、ガン細胞そのものだけでなく、正常な細胞にもダメージがおよび、免疫力や自然治癒力の低下に伴って、結果として、患者が亡くなってしまうケースが非常に多いという問題があった。このような経緯を経て、副作用の少ない安全な治療法に対する要望は日々高まりを見せており、病気の治療よりも予防に重点がおかれるようになっている。 Cancer has been the leading cause of death in Japan since 1981. Among the three major causes of death, only cancer has consistently increased and the number of deaths continues to increase. According to the Ministry of Health, Labor and Welfare's demographic statistics, out of 97,331 deaths in 2001, 300,658 died from cancer, and one in three died from cancer. It will be. For such diseases, the main treatment currently performed in hospitals is symptomatic treatment in which cancer cells are directly attacked by various therapies such as drugs, chemistry, and physics. Not only that, normal cells are damaged, and there is a problem that patients often die as a result of a decrease in immunity and natural healing power. With this background, the demand for safe treatments with few side effects is increasing day by day, and more emphasis is placed on prevention than disease treatment.
近年、安全なガンの治療法として血管新生阻害を応用することが注目されている。ガン細胞は、血管新生促進物質を産生することで、自らの細胞に栄養分や酸素を送り込む血液の経路を張りめぐらし、十分な血液を供給し続け、爆発的な増殖を繰り返すという性質を持っているが、血管新生阻害作用を応用したガン治療とは、ガン細胞への血液の経路を遮断してガン細胞の増殖を防ぐものである。すなわち、簡単に言えば、ガン細胞を兵糧攻めにするということである。 In recent years, the application of angiogenesis inhibition as a safe cancer treatment has attracted attention. By producing angiogenesis-promoting substances, cancer cells have the property of spreading blood and feeding nutrients and oxygen to their cells, supplying enough blood, and repeating explosive growth. However, cancer treatment applying an angiogenesis inhibitory action is to prevent the proliferation of cancer cells by blocking the blood pathway to the cancer cells. That is, to put it simply, cancer cells are attacked.
血管新生抑制の作用は、ガンのみではなく、リウマチ様関節炎、糖尿病、心臓病、その他様々な疾患に対して予防および安全に治療する効果があることが近年報告されており、（非特許文献1〜３）血管新生抑制作用を有する物質の早期提供が強く求められている。 In recent years, it has been reported that the action of inhibiting angiogenesis has the effect of preventing and safely treating not only cancer but also rheumatoid arthritis, diabetes, heart disease and other various diseases (Non-patent Document 1 ~ 3) Early provision of a substance having an anti-angiogenic action is strongly demanded.
血管新生阻害作用を有する天然物由来の活性成分について、特許文献１には、ヤシ科植物の果皮や種子から得られるトコトリエノールを有効成分とする血管新生阻害剤、細胞増殖阻害剤、管腔形成阻害剤およびＦＧＦ阻害剤並びに食品或いは食品添加物が記載されており、特許文献２には、シイタケ菌糸体抽出物を含む血管新生を阻害するための食品組成物が記載されている。特許文献３および４には、糸状菌を培養し、その培養液から得られた新規な化合物が、血管新生阻害作用を有することが記載されている。 Regarding an active ingredient derived from a natural product having an angiogenesis inhibitory action, Patent Document 1 discloses an angiogenesis inhibitor, a cell growth inhibitor, and a lumen formation inhibitor containing tocotrienol obtained from palm skin and seeds as an active ingredient. Agents and FGF inhibitors and foods or food additives are described, and Patent Document 2 describes a food composition for inhibiting angiogenesis including shiitake mycelium extract. Patent Documents 3 and 4 describe that a novel compound obtained by culturing a filamentous fungus and obtained from the culture solution has an angiogenesis inhibitory effect.
ところで、イネ科植物である大麦は、有史以前から人類に欠かせない穀類で、日本の古い医学書にも記載されているなど、健康に良い食品として親しまれてきた。実際に大麦や大麦を微生物にて発酵させたものの生理活性機能については様々な研究が行われてきた。 By the way, barley, a gramineous plant, has been indispensable for humankind since prehistoric times, and has been loved as a healthy food, as described in old Japanese medical books. Various studies have been conducted on the physiologically active function of barley or barley fermented with microorganisms.
特許文献５には、大麦類を爆砕処理したものを水性溶媒で抽出することにより、主としてその穀皮画分からの抽出エキスが有用な生理活性作用、すなわち免疫増強作用、血圧降下作用、血流改善作用、アンジオテンシンＩ変換酵素阻害作用、抗菌作用などの生理活性作用を有し、それを利用した機能性食品素材が記載されている。しかしながらこの発明は、大麦の穀皮画分からの抽出エキスであり、その有効成分は、水易溶性物質であり、分子量５０万以下で、主成分が分子量１０万以下、タンパク質含量３〜３０％、水溶性のフェルラ酸およびｐ−クマル酸に富んでいるものである。 Patent Document 5 discloses that an extract obtained from a crushed fraction of barley is extracted with an aqueous solvent, so that an extract mainly from the husk fraction is useful for bioactivity, that is, immune enhancement, blood pressure lowering, and blood flow improvement. Functional food materials that have physiological activity such as action, angiotensin I converting enzyme inhibitory action, and antibacterial action are described. However, this invention is an extract extracted from the bark grain fraction, its active ingredient is a readily water-soluble substance, has a molecular weight of 500,000 or less, the main component is a molecular weight of 100,000 or less, a protein content of 3 to 30%, It is rich in water-soluble ferulic acid and p-coumaric acid.
大麦を原料とする焼酎製造において副成する大麦焼酎蒸留残液を利用した発明として、特許文献６には、大麦焼酎蒸留残液を固液分離して液体分を得、該液体分にアルカリを添加してアルカリ可溶性画分を分取し、該アルカリ可溶性画分を酸で中和して中性可溶性画分を得、該中性可溶性画分にエタノールを添加することにより分取した、有機酸、タンパク質、およびヘミセルロースを含有するエタノール不溶性画分が、脂肪肝抑制作用を有することが記載されており、特許文献７には、大麦焼酎蒸留残液を固液分離して液体分を得、該液体分に有機溶媒を添加することにより分取した有機溶媒不溶性画分が、白血病細胞増殖阻害作用を有することが記載されており、特許文献８には、大麦焼酎蒸留残液から、特許文献７と同様にして得られた有機溶媒不溶性画分が、ナチュラルキラー細胞を賦活化することが記載されている。 As an invention using a barley shochu distillation residue as a by-product in the production of shochu using barley as a raw material, Patent Document 6 discloses a liquid component obtained by solid-liquid separation of the barley shochu distillation residue, and an alkali is added to the liquid component. To add an alkali-soluble fraction, neutralize the alkali-soluble fraction with an acid to obtain a neutral soluble fraction, and add the ethanol to the neutral soluble fraction. It is described that an ethanol-insoluble fraction containing acid, protein, and hemicellulose has a fatty liver inhibitory action, and Patent Document 7 obtains a liquid component by solid-liquid separation of a barley shochu distillation residue, It is described that an organic solvent-insoluble fraction collected by adding an organic solvent to the liquid component has an inhibitory effect on leukemia cell growth. Patent Document 8 discloses from a barley shochu distillation residue, Patent Document Obtained in the same way as 7. The organic solvent-insoluble fraction, it is described that the activation of natural killer cells.
特許文献９には、大麦焼酎蒸留残液を固液分離して液体分を得、該液体分を合成吸着剤に付すことにより分取した非吸着画分からなり、該非吸着画分は、平均鎖長が３．０ないし５．０である複数種のペプチドを含有し、それらペプチドは該ペプチドに由来するアミノ酸総含量を１００％としたときのアミノ酸組成が、グルタミン酸２４ないし３８％、グリシン４ないし２０％、アスパラギン酸５ないし１０％、プロリン４ないし９％、およびセリン４ないし８％であり、アルコール性肝障害に対する発症抑制作用および治癒作用を有し且つ優れた呈味性を有する食品用組成物およびその製造方法が記載されている。特許文献１０には、特許文献９と同様にして得られた組成物が、アルコール性肝障害に対する発症抑制作用および治癒作用を有する医薬組成物およびその製造方法が記載されている。 Patent Document 9 includes a non-adsorbed fraction obtained by solid-liquid separation of a barley shochu distillation residue and applying the liquid to a synthetic adsorbent, and the non-adsorbed fraction has an average chain. A plurality of peptides having a length of 3.0 to 5.0 are contained, and these peptides have an amino acid composition of glutamic acid 24 to 38%, glycine 4 to 20%, aspartic acid 5 to 10%, proline 4 to 9%, and serine 4 to 8%, and has a suppressive action and curative action on alcoholic liver damage and has an excellent taste. Products and methods for their production are described. Patent Document 10 describes a pharmaceutical composition in which the composition obtained in the same manner as Patent Document 9 has an onset suppressing action and a healing action against alcoholic liver injury, and a method for producing the same.
また、特許文献１１には、大麦焼酎蒸留残液を固液分離して液体分を得、該液体分をイオン交換処理に付してイオン交換樹脂非吸着画分を得、該イオン交換樹脂非吸着画分を限外濾過処理に付して濃縮液を得、該濃縮液に有機溶媒を添加することにより分取した有機溶媒不溶性画分が、抗酸化作用を有することが記載されている。 Further, in Patent Document 11, a barley shochu distillation residue is subjected to solid-liquid separation to obtain a liquid component, which is subjected to an ion exchange treatment to obtain an ion-exchange resin non-adsorbed fraction. It is described that the organic solvent-insoluble fraction obtained by subjecting the adsorbed fraction to ultrafiltration treatment to obtain a concentrated liquid and adding an organic solvent to the concentrated liquid has an antioxidant action.
大麦および大麦の発酵物には、前記したように、様々な生理活性があることが確かめられてきたがその生理活性の中に血管新生阻害作用は含まれておらず、大麦が血管新生阻害作用を呈するということはこれまで知られていなかった。 As described above, barley and fermented barley have been confirmed to have various physiological activities, but the angiogenesis inhibitory action is not included in the physiological activities. It has not been known so far.
本発明は、安全性に問題がなく、安価で比較的容易に入手可能な材料、好ましくは大麦から、煩雑な精製工程を経ず、工場規模での実生産に適した簡便な処理方法により、優れた血管新生阻害作用を有する組成物を提供すること、好ましくは血管新生を阻害すべき疾患を治療または予防するための組成物、より具体的には食品添加物、食品素材、飲食品、医薬品・医薬部外品および飼料からなる群から選ばれる形態のものを提供することを課題とする。 The present invention has no problem in safety, is inexpensive and relatively easily available, preferably from barley, without complicated purification steps, by a simple processing method suitable for actual production on a factory scale, Providing a composition having an excellent angiogenesis inhibitory effect, preferably a composition for treating or preventing a disease that should inhibit angiogenesis, more specifically, a food additive, a food material, a food and drink, and a pharmaceutical product -It aims at providing the thing of the form chosen from the group which consists of a quasi-drug and feed.
本発明者らは、上記課題を解決するために、鋭意研究した結果、穀類由来の成分、特に大麦由来の成分に優れた血管新生阻害作用が存在することを見いだし、発明をなした。本発明において、大麦玄麦エチルアルコール抽出画分、大麦玄麦アルカリ抽出画分が、有意な血管新生の阻害作用を有すること、これにより、副作用が少ない、血管新生阻害活性を有する組成物を新たに提供することができる。 As a result of intensive studies to solve the above problems, the present inventors have found that an excellent angiogenesis inhibitory action exists in cereal-derived components, particularly barley-derived components, and have made an invention. In the present invention, the barley brown barley ethyl alcohol extract fraction and the barley brown bark alkali extract fraction have a significant angiogenesis inhibitory action, thereby providing a composition having angiogenesis inhibitory activity with fewer side effects. can do.
すなわち、本発明は、以下の（１）〜（８）の血管新生を阻害するための組成物を要旨とする。
（１）イネ科植物由来の成分を血管新生阻害作用の有効成分とすることを特徴とする血管新生を阻害するための組成物。
（２）イネ科植物由来の成分が大麦由来の成分である（１）の血管新生を阻害するための組成物。
（３）上記大麦由来の成分が大麦玄麦エチルアルコール抽出画分および大麦玄麦アルカリ抽出画分からなる群より選ばれる（２）の血管新生を阻害するための組成物。
（４）上記血管新生を阻害するための組成物が、血管新生を阻害すべき疾患を治療または予防するための組成物である（１）、（２）または（３）の血管新生を阻害するための組成物。
（５）上記血管新生を阻害すべき疾患が、腫瘍もしくは癌、慢性炎症または網膜症における異常な血管新生が原因となる疾患である（４）の血管新生を阻害するための組成物。
（６）上記組成物が、血管新生を阻害するための食品添加物、食品素材、飲食品、医薬品・医薬部外品および飼料からなる群から選ばれる形態のものである（１）ないし（５）のいずれかの血管新生を阻害するための組成物。
（７）上記飲食品が、血管新生を阻害するための、機能性食品、栄養補助食品または健康飲食品である（６）の血管新生を阻害するための組成物。
（８）上記飼料が、血管新生を阻害するための、家畜、家禽、ペット類の飼料である（６）の血管新生を阻害するための組成物。
That is, the gist of the present invention is a composition for inhibiting angiogenesis of the following (1) to (8).
(1) A composition for inhibiting angiogenesis, which comprises using a component derived from a gramineous plant as an active ingredient of an angiogenesis inhibitory action.
(2) The composition for inhibiting angiogenesis of (1), wherein the component derived from the grass family is a component derived from barley.
(3) The composition for inhibiting angiogenesis in (2), wherein the barley-derived component is selected from the group consisting of a barley brown barley ethyl alcohol extract fraction and a barley brown barley alkali extract fraction.
(4) The composition for inhibiting angiogenesis is a composition for treating or preventing a disease for which angiogenesis should be inhibited, and inhibits angiogenesis in (1), (2) or (3). Composition for.
(5) The composition for inhibiting angiogenesis according to (4), wherein the disease to inhibit angiogenesis is a disease caused by abnormal angiogenesis in a tumor or cancer, chronic inflammation or retinopathy.
(6) The composition is in a form selected from the group consisting of food additives for inhibiting angiogenesis, food materials, food and drink, pharmaceuticals / quasi drugs, and feed (1) to (5) ) A composition for inhibiting angiogenesis.
(7) The composition for inhibiting angiogenesis according to (6), wherein the food or drink is a functional food, a nutritional supplement or a health food or drink for inhibiting angiogenesis.
(8) The composition for inhibiting angiogenesis according to (6), wherein the feed is a feed for livestock, poultry and pets for inhibiting angiogenesis.
本発明は、安全性に問題がなく、安価で比較的容易に入手可能な材料（大麦玄麦）から、煩雑な精製工程を経ず、工場規模での実生産に適した簡便な処理方法により、副作用が少ない、血管新生阻害活性を有する組成物、好ましくは血管新生を阻害すべき疾患を治療または予防するための組成物、より具体的には食品添加物、食品素材、飲食品、医薬品・医薬部外品および飼料からなる群から選ばれる形態のものを提供することができる。 The present invention has no problem in safety, is inexpensive and relatively easily available material (barley brown barley), without a complicated purification process, by a simple processing method suitable for actual production on a factory scale, A composition having an angiogenesis inhibitory activity with few side effects, preferably a composition for treating or preventing a disease that should inhibit angiogenesis, more specifically, a food additive, a food material, a food or drink, a pharmaceutical product / medicine The thing of the form chosen from the group which consists of a quasi-drug and a feed can be provided.
本発明に記載の血管新生阻害活性を有する組成物は、たとえば大麦、小麦、ライ麦、オーツ麦、はと麦、米などのイネ科の植物から調製できるが、大麦を用いることが好ましい。大麦は、皮麦、裸麦のどちらでも良く、また二条大麦、六条大麦のどちらでも良い。また穀表部に色素が沈着した有色大麦でも良い。穀物の形態としては、穀粒全体、表皮部、胚乳など特に制限されないが、玄麦などの穀粒全体を用いることが好ましい。また、焙煎処理や製粉処理、圧偏処理などの加工処理を加えても良い。 The composition having angiogenesis inhibitory activity described in the present invention can be prepared from a plant of the family Gramineae such as barley, wheat, rye, oats, hard wheat and rice, but barley is preferably used. Barley may be either barley or bare barley, or may be either Nijo barley or Rojo barley. Colored barley with pigments deposited on the grain surface may also be used. The form of the grain is not particularly limited, such as the whole grain, epidermis, endosperm, etc., but it is preferable to use the whole grain such as brown wheat. In addition, processing such as roasting, milling, and pressure biasing may be added.
本発明の上記組成物は、安全性に問題がなく、安価で比較的容易に入手可能な材料（イネ科植物）、好ましくは大麦から、煩雑な精製工程を経ず、工場規模での実生産に適した簡便な処理方法により得られ、その生体への適用は飲食物、医薬品、肥料、飼料や皮膚外用剤に使用することで、優れた血管新生阻害効果を得ることが期待できる。
本発明の上記組成物は、血管新生阻害作用を有する天然物由来の活性成分を有するものであり、該活性成分に基づく血管新生阻害を応用することにより、たとえば安全なガンの治療法へと導くのであり、血管新生抑制の作用は、ガンのみではなく、リウマチ様関節炎、糖尿病、心臓病、その他様々な疾患に対して予防および安全に治療する効果を有する機能性組成物である。
すなわち、本発明の上記組成物は、血管新生を阻害すべき疾患を治療または予防するための組成物である。血管新生を阻害すべき疾患とは、血管新生が病態の発生に重要な働きをしている疾患であれば、どのようなものでも対象となる。したがって、血管新生を阻害すべき疾患は、腫瘍もしくは癌、慢性炎症または網膜症における異常な血管新生が原因となる疾患である。より具体的には、血管新生を阻害すべき疾患は例えば、種々の組織に発生する固型腫瘍、骨髄腫、血管腫などの腫瘍もしくは癌；慢性関節性リウマチ、乾癬、変形性関節症などの慢性炎症；または加齢性黄斑変性症、糖尿病性網膜症、新生血管緑内障などの網膜症；などの疾患をあげることができるが、これらのものには限定されない。本発明においては、血管新生を阻害すべき疾患として、種々の腫瘍または癌を標的とすることが好ましい。
The above composition of the present invention has no problem in safety, and is produced from a cheap and relatively easily available material (Poaceae), preferably barley, on a factory scale without complicated purification steps. It can be expected to obtain an excellent angiogenesis inhibitory effect when applied to foods, drinks, pharmaceuticals, fertilizers, feeds and skin external preparations.
The composition of the present invention has an active ingredient derived from a natural product having an angiogenesis inhibitory action, and by applying angiogenesis inhibition based on the active ingredient, for example, leads to a safe cancer treatment method. Therefore, the action of inhibiting angiogenesis is a functional composition having an effect of preventing and safely treating not only cancer but also rheumatoid arthritis, diabetes, heart disease and other various diseases.
That is, the composition of the present invention is a composition for treating or preventing a disease that should inhibit angiogenesis. The disease that should inhibit angiogenesis is a target as long as it is a disease in which angiogenesis plays an important role in the pathogenesis. Thus, diseases that should inhibit angiogenesis are diseases caused by abnormal angiogenesis in tumors or cancer, chronic inflammation or retinopathy. More specifically, diseases that should inhibit angiogenesis include, for example, solid tumors, myelomas, hemangiomas and other tumors or cancers that occur in various tissues; rheumatoid arthritis, psoriasis, osteoarthritis, etc. Diseases such as, but not limited to, chronic inflammation; or retinopathy such as age-related macular degeneration, diabetic retinopathy, neovascular glaucoma; In the present invention, it is preferable to target various tumors or cancers as diseases for inhibiting angiogenesis.
本発明の組成物が有する血管新生阻害活性をin vitroにおいて調べるためには、培養条件下で血管内皮細胞と線維芽細胞とを、必要に応じて血管新生誘導性因子であるVEGFの存在下にて、共培養させることにより管腔形成初期段階の増殖状態が作り出された培養中に、本発明の組成物を添加して、血管新生の抑制が生じるかどうかを確認することができる。血管新生の抑制は、例えば管腔を染色して管腔形成が抑制されているかどうかを調べることにより行うことができる。このようなin vitroにおける血管新生の阻害効果を調べるためのキットとしては、血管新生キット（KURABO社製）を、管腔を染色するためには抗CD31抗体や抗フォン-ウィルブランド因子抗体などの抗体を使用する管腔染色キット（KURABO社製）を、それぞれ使用することができる。 In order to examine the angiogenesis inhibitory activity of the composition of the present invention in vitro, vascular endothelial cells and fibroblasts are cultured under culture conditions in the presence of VEGF, an angiogenesis-inducing factor, as necessary. Thus, it is possible to confirm whether or not angiogenesis is suppressed by adding the composition of the present invention to the culture in which the growth state at the initial stage of tube formation is created by co-culture. Inhibition of angiogenesis can be performed, for example, by staining a lumen to examine whether or not the lumen formation is suppressed. As a kit for investigating the inhibitory effect of angiogenesis in vitro, an angiogenesis kit (manufactured by KURABO) can be used, and an anti-CD31 antibody or an anti-von Willebrand factor antibody can be used to stain a lumen. A luminal staining kit using an antibody (manufactured by KURABO) can be used.
本発明の上記組成物は、大麦由来の成分を血管新生阻害作用の有効成分とすることを特徴とする。前記大麦由来の成分に含まれる血管新生阻害作用を呈する物質は、好ましくは大麦玄麦エタノール抽出画分、大麦玄麦アルカリ抽出画分に含まれる物質である。 The composition of the present invention is characterized in that an ingredient derived from barley is used as an active ingredient for inhibiting angiogenesis. The substance exhibiting angiogenesis-inhibiting action contained in the barley-derived component is preferably a substance contained in the barley brown wheat ethanol extract fraction and the barley brown wheat alkali extract fraction.
大麦玄麦エタノール抽出画分を得る方法としては、大麦玄麦をミルで粉砕したものにエタノールを加え抽出し、抽出液をろ紙にてろ過後、ろ液を減圧濃縮し、エタノールを除去し、遠心分離して大麦玄麦エタノール抽出液の液体分を得る方法が例示される。玄麦アルカリ抽出画分を得る方法としては、大麦玄麦をミルで粉砕したものにアルカリ水溶液を加えて抽出液を得、酸を用いて該抽出液を中和し、続いて、ろ紙にてろ過して大麦玄麦アルカリ抽出液の液体分を得る方法が例示される。 As a method of obtaining the barley brown barley ethanol extraction fraction, the barley brown barley was crushed with a mill and extracted with ethanol. The filtrate was filtered through a filter paper, the filtrate was concentrated under reduced pressure, ethanol was removed, and centrifugation was performed. And the method of obtaining the liquid part of a barley brown wheat ethanol extract is illustrated. As a method for obtaining a brown barley alkaline extract fraction, an aqueous alkaline solution is added to a barley brown barley crushed with a mill to obtain an extract, and the extract is neutralized with an acid, followed by filtration with filter paper. And a method for obtaining the liquid content of the barley brown barley alkaline extract.
大麦玄麦エタノール抽出物、および／または大麦玄麦アルカリ抽出画分は、血管新生を阻害するための食品添加物、食品素材、飲食品、医薬品・医薬部外品および飼料からなる群から選ばれる形態のものである。その組成物の機能性を生かして健康飲食品、患者用栄養飲食品を謳った食品、同様に、家畜、家禽、魚などの飼育動物のための飼料の開発が可能となった。
すなわち、上記飲食品が、血管新生を阻害するための、機能性食品、栄養補助食品または健康飲食品である。上記飼料が、血管新生を阻害するための、家畜、家禽、ペット類の飼料である。具体的には、上述した玄麦エタノール抽出物を含む食品素材を、食品形態、飲料形態または飼料形態のいずれの形態で使用することができる。
本発明の血管新生を阻害するための組成物が有する上述した機能性を生かして用いる場合は、その含量は、特に制限されないが、目的とする機能の度合い、使用態様、使用量等により適宜調整することができ、例えば０．００１〜１００質量％である。本血管新生を阻害するための組成物は、人体やその他飲食物、医薬品、飼料や皮膚外用剤に使用することができる。また、経口等により内服することも、皮膚等に塗布することもできる。常法にしたがって経口、非経口の製品に配合することができ、調味料、食品添加物、食品素材、飲食品、健康飲食品、皮膚外用剤、医薬品および飼料等の様々な分野で利用することができる。例えば、飲食物に配合した場合には、血管新生を阻害すべき疾患を治療または予防するための飲食物を提供することができる。予防等の効果からは、健康食品、栄養食品等として用いられることも期待できる。その他、家畜、および／または魚類の飼料、餌料に利用することができる。人体やその他飲食物、医薬品、肥料、飼料や皮膚外用剤に使用することにより、血管新生を阻害すべき疾患を治療または予防する効果を得ることができる。
さらに、大麦玄麦から容易に得ることができ、コスト面からみても、資源の有効活用という面からみても好ましい。
The barley brown barley ethanol extract and / or barley brown bark alkali extract fraction is in a form selected from the group consisting of food additives, food ingredients, food and drink, pharmaceuticals / quasi drugs, and feed for inhibiting angiogenesis. Is. Utilizing the functionality of the composition, it has become possible to develop healthy foods and drinks, foods containing nutritional foods and drinks for patients, and feeds for domestic animals such as livestock, poultry and fish.
That is, the said food / beverage products are a functional food, a nutritional supplement, or a health food / beverage product for inhibiting angiogenesis. The feed is a feed for livestock, poultry and pets for inhibiting angiogenesis. Specifically, the food material containing the brown wheat ethanol extract described above can be used in any form of food form, beverage form or feed form.
In the case of using the above-described functionality of the composition for inhibiting angiogenesis of the present invention, the content is not particularly limited, but is appropriately adjusted depending on the degree of intended function, usage mode, usage amount, etc. For example, it is 0.001-100 mass%. The composition for inhibiting the angiogenesis can be used for the human body, other foods and drinks, pharmaceuticals, feeds and external preparations for skin. It can also be taken orally or applied to the skin. Can be incorporated into oral and parenteral products according to conventional methods and used in various fields such as seasonings, food additives, food ingredients, food and drink, health food and drink, topical skin preparations, pharmaceuticals and feed Can do. For example, when blended with food or drink, food or drink for treating or preventing a disease that should inhibit angiogenesis can be provided. From the effect of prevention, it can be expected to be used as health food, nutritional food and the like. In addition, it can be used for livestock and / or fish feed and feed. By using it for the human body and other foods and drinks, pharmaceuticals, fertilizers, feeds and external preparations for skin, it is possible to obtain an effect of treating or preventing a disease that should inhibit angiogenesis.
Furthermore, it can be easily obtained from barley brown barley, which is preferable from the viewpoint of cost and effective utilization of resources.
本発明の組成物を食品に利用する場合、そのままの形態、オイルなどに希釈した形態、乳液状形態食、または食品業界で一般的に使用される担体を添加した形態などのものを調製してもよい。
乳液状形態のものは、例えば、油相部に組成物を添加し、更にグリセリン脂肪酸エステル、ソルビタン脂肪酸エステル、ショ糖脂肪酸エステル、グリセロール、デキストリン、ナタネ油、大豆油、コーン油などの液状の脂肪を加え、水相部にＬ−アスコルビン酸或いはそのエステルまたは塩、例えばローカストビーンガム、アラビアガムまたはゼラチンなどのガム質、例えばヘスペリジン、ルチン、ケルセチン、カテキン、チアニジンなどのフラボノイド類またはポリフェノール類或いはその混合物などを添加し、乳化することによって調製できる。
When the composition of the present invention is used for food, it can be prepared as it is, in a form diluted with oil, a milk form meal, or a form to which a carrier generally used in the food industry is added. Also good.
In the case of the emulsion form, for example, the composition is added to the oil phase part, and liquid fat such as glycerin fatty acid ester, sorbitan fatty acid ester, sucrose fatty acid ester, glycerol, dextrin, rapeseed oil, soybean oil, corn oil, etc. L-ascorbic acid or an ester or salt thereof, for example, gum such as locust bean gum, gum arabic or gelatin, for example, flavonoids such as hesperidin, rutin, quercetin, catechin, thianidine or polyphenols or the like It can be prepared by adding a mixture and emulsifying.
飲料の形態は、非アルコール飲料またはアルコール飲料である。非アルコール飲料としては、例えば、炭酸系飲料、果汁飲料、ネクター飲料などの非炭酸系飲料、清涼飲料、スポーツ飲料、茶、コーヒー、ココアなど、また、アルコール飲料の形態ではスピリッツ、リキュール、チューハイ、果実酒類、麦酒、発泡酒、薬用酒などの一般食品の形態を挙げることができる。 The form of the beverage is a non-alcoholic beverage or an alcoholic beverage. Non-alcoholic beverages include, for example, non-carbonated beverages such as carbonated beverages, fruit juice beverages, and nectar beverages, soft drinks, sports beverages, tea, coffee, cocoa, etc. The form of general foods, such as fruit liquor, barley liquor, Happoshu, and medicinal liquor, can be mentioned.
飲食物としては、具体的には以下のものを例示することができる。洋菓子類（プリン、ゼリー、グミキャンディー、キャンディー、ドロップ、キャラメル、チューインガム、チョコレート、ペストリー、バタークリーム、カスタードグリーム、シュークリーム、ホットケーキ、パン、ポテトチップス、フライドポテト、ポップコーン、ビスケット、クラッカー、パイ、スポンジケーキ、カステラ、ワッフル、ケーキ、ドーナツ、ビスケット、クッキー、せんべい、おかき、おこし、まんじゅう、あめなど）、乾燥麺製品（マカロニ、パスタ）、卵製品（マヨネーズ、生クリーム）、飲料（機能性飲料、乳酸飲料、乳酸菌飲料、濃厚乳性飲料、果汁飲料、無果汁飲料、果肉飲料、透明炭酸飲料、果汁入り炭酸飲料、果実着色炭酸飲料）、嗜好品（緑茶、紅茶、インスタントコーヒー、ココア、缶入りコーヒードリンク）、乳製品（アイスクリーム、ヨーグルト、コーヒー用ミルク、バター、バターソース、チーズ、発酵乳、加工乳）、ペースト類（マーマレード、ジャム、フラワーペースト、ピーナッツペースト、フルーツペースト、果実のシロップ漬け）、畜肉製品（ハム、ソーセージ、ベーコン、ドライソーセージ、ビーフジャーキー、ラード）、魚介類製品（魚肉ハム、魚肉ソーセージ、蒲鉾、ちくわ、ハンペン、魚の干物、鰹節、鯖節、煮干し、うに、いかの塩辛、スルメ、魚のみりん干し、貝の干物、鮭などの燻製品）、佃煮類（小魚、貝類、山菜、茸、昆布）、カレー類（即席カレー、レトルトカレー、缶詰カレー）、調味料剤（みそ、粉末みそ、醤油、粉末醤油、もろみ、魚醤、ソース、ケチャップ、オイスターソース、固形ブイヨン、焼き肉のたれ、カレールー、シチューの素、スープの素、だしの素、ペースト、インスタントスープ、ふりかけ、ドレッシング、サラダ油）、揚げ製品（油揚げ、油揚げ菓子、即席ラーメン）、豆乳、マーガリン、ショートニングなどを挙げることができる。 Specific examples of food and drink include the following. Pastry (pudding, jelly, gummy candy, candy, drop, caramel, chewing gum, chocolate, pastry, butter cream, custard cream, cream puff, hot cake, bread, potato chips, french fries, popcorn, biscuits, crackers, pie, sponge Cakes, castella, waffles, cakes, donuts, biscuits, cookies, rice crackers, rice crackers, rice cakes, manju, candy, etc., dried noodle products (macaroni, pasta), egg products (mayonnaise, fresh cream), beverages (functional beverages, Lactic acid beverages, lactic acid bacteria beverages, concentrated dairy beverages, fruit juice beverages, fruit juice beverages, pulp beverages, transparent carbonated beverages, carbonated beverages with fruit juice, fruit colored carbonated beverages), luxury products (green tea, tea, instant coffee, cocoa, canned Coffee Milk), dairy products (ice cream, yogurt, coffee milk, butter, butter sauce, cheese, fermented milk, processed milk), pastes (marmalade, jam, flower paste, peanut paste, fruit paste, fruit syrup) , Livestock meat products (ham, sausage, bacon, dry sausage, beef jerky, lard), seafood products (fish meat ham, fish sausage, salmon, chikuwa, hampen, dried fish, bonito, bonito, boiled, sea urchin Salted fish, plums, dried fish, shellfish, salmon products such as salmon), boiled fish (small fish, shellfish, wild vegetables, salmon, kelp), curry (improvised curry, retort curry, canned curry), seasoning (Miso, powdered miso, soy sauce, powdered soy sauce, moromi, fish sauce, sauce, ketchup, oyster sauce, solid bouillon List of grilled meat sauce, curry roux, stew sauce, soup sauce, soup stock, paste, instant soup, sprinkle, dressing, salad oil), fried products (fried food, fried confectionery, instant ramen), soy milk, margarine, shortening, etc. be able to.
上記飲食物は、組成物を常法に従って、一般食品の原料と配合することにより、加工製造することができる。 The said food and drink can be processed and manufactured by mix | blending a composition with the raw material of a general food according to a conventional method.
上記飲食物への組成物の配合量は食品の形態により異なり特に限定されるものではないが、通常は０．００１〜２０％が好ましい。 Although the compounding quantity of the composition to the said food-drinks changes with forms of food and is not specifically limited, Usually, 0.001 to 20% is preferable.
上記飲食物は、機能性食品、栄養補助食品或いは健康食品類としても用いることができる。その形態は、特に限定されるものではなく、例えば、食品の製造例としては、アミノ酸バランスのとれた栄養価の高い乳蛋白質、大豆蛋白質、卵アルブミンなどの蛋白質、これらの分解物、卵白のオリゴペプチド、大豆加水分解物などの他、アミノ酸単体の混合物などを、常法に従って使用することができる。また、ソフトカプセル、タブレットなどの形態で利用することもできる。 The above food and drink can also be used as functional foods, nutritional supplements or health foods. The form is not particularly limited, and examples of food production include milk proteins with high amino acid balance, soy protein, and proteins such as egg albumin, degradation products thereof, and egg white oligos. In addition to peptides, soybean hydrolysates, and the like, mixtures of amino acids alone can be used according to conventional methods. It can also be used in the form of a soft capsule, a tablet or the like.
栄養補助食品或いは機能性食品の例としては、糖類、脂肪、微量元素、ビタミン類、乳化剤、香料などが配合された流動食、半消化態栄養食、成分栄養食、ドリンク剤、カプセル剤、経腸栄養剤などの加工形態を挙げることができる。上記各種食品には、例えば、スポーツドリンク、栄養ドリンクなどの飲食物は、栄養バランス、風味を良くするために、更にアミノ酸、ビタミン類、ミネラル類などの栄養的添加物や甘味料、香辛料、香料、色素などを配合することもできる。 Examples of dietary supplements or functional foods include liquid foods, semi-digested nutritional foods, ingredient nutritional foods, drinks, capsules, and sucrose containing sugars, fats, trace elements, vitamins, emulsifiers, and fragrances. Processing forms such as enteral nutrients can be mentioned. In the above-mentioned various foods, for example, foods and drinks such as sports drinks and nutritional drinks are further supplemented with nutritional additives such as amino acids, vitamins and minerals, sweeteners, spices and fragrances to improve nutritional balance and flavor. , Pigments and the like can also be blended.
本発明の組成物を安定化させるために抗酸化剤、例えば、トコフェロール、Ｌ−アスコルビン酸、ＢＨＡ、ローズマリー抽出物などを常法に従って併用することができる。 In order to stabilize the composition of the present invention, an antioxidant such as tocopherol, L-ascorbic acid, BHA, rosemary extract and the like can be used in combination according to a conventional method.
本発明の組成物は、家畜、家禽、ペット類の飼料用に応用することができる。例えば、ドライドッグフード、ドライキャットフード、ウェットドッグフード、ウェットキャットフード、セミモイストドックフード、養鶏用飼料、牛、豚などの家畜用飼料に配合することができる。飼料自体は、常法に従って調製することができる。
これらの治療剤および予防剤は、ヒト以外の動物、例えば、牛、馬、豚、羊などの家畜用哺乳類、鶏、ウズラ、ダチョウなどの家禽類、は虫類、鳥類或いは小型哺乳類などのペット類、養殖魚類などにも用いることができる。
The composition of the present invention can be applied to feed for livestock, poultry and pets. For example, it can mix | blend with livestock feeds, such as dry dog food, dry cat food, wet dog food, wet cat food, semi-moist dock food, poultry feed, cattle, and pigs. The feed itself can be prepared according to a conventional method.
These therapeutic agents and preventive agents are non-human animals, for example, domestic mammals such as cattle, horses, pigs and sheep, poultry such as chickens, quails and ostriches, reptiles, birds and pets such as small mammals, It can also be used for farmed fish.
以下に、大麦玄麦を材料とした各組成物の調整法と、血管新生阻害効果について説明するが、本発明の範囲はこれらの例示に限定されるものではない。 Although the preparation method of each composition which uses barley brown barley as a material, and the angiogenesis inhibitory effect are demonstrated below, the scope of the present invention is not limited to these illustrations.
本発明の詳細を実施例で示す。本発明はこれらの実施例によって何ら限定されるものではない。 Details of the invention are given in the examples. The present invention is not limited by these examples.
［実験１］
血管新生阻害実験
〈サンプル名称〉
表１に示すとおり。
A1、A2：ネガティブコントロール
A3、A4：ポジティブコントロール
B1〜B3：玄麦エタノール抽出画分粉末
C1〜C3：玄麦アルカリ抽出画分粉末
[Experiment 1]
Angiogenesis inhibition experiment <sample name>
As shown in Table 1.
A1, A2: Negative control
A3, A4: Positive control
B1-B3: Brown wheat ethanol extract fraction powder
C1-C3: Brown wheat alkali extract fraction powder
〈血管新生阻害実験に用いたサンプルの調製法〉
本実験に用いたサンプルについては、他の実験との兼ね合いがあり、粉末化したサンプルを再溶解して実験に用いているが、液状のまま、実験に用いても何ら問題はない。
<Preparation method of sample used for angiogenesis inhibition experiment>
The sample used in this experiment has a balance with other experiments, and the powdered sample is redissolved and used in the experiment. However, there is no problem even if it is used in the experiment as it is in a liquid state.
［玄麦エタノール抽出画分粉末］
大麦玄麦をミルで粉砕したもの100gに75%（v/v）エタノール1Lを加え、常温で6時間撹拌抽出した。抽出液を、ADVANTEC社製4Cろ紙にてろ過後、該ろ液を減圧濃縮し、エタノールを除去した。続いて、10000 rpm、10 minの条件で遠心分離して該大麦玄麦エタノール抽出液の液体分を得、該抽出液を凍結乾燥に付した。
[Brown ethanol extraction fraction powder]
1 L of 75% (v / v) ethanol was added to 100 g of barley brown barley crushed with a mill, and the mixture was stirred and extracted at room temperature for 6 hours. The extract was filtered through 4C filter paper manufactured by ADVANTEC, and the filtrate was concentrated under reduced pressure to remove ethanol. Subsequently, the mixture was centrifuged at 10,000 rpm for 10 min to obtain a liquid content of the barley brown wheat ethanol extract, and the extract was freeze-dried.
［玄麦アルカリ抽出画分粉末］
大麦玄麦をミルで粉砕したもの100gに2%Ca(OH)2水溶液1 Lを加え、常温で6時間撹拌抽出した後、HCLを用いて、該抽出液のpHを7.0に調製した。続いて、ADVANTEC社製4Cろ紙にてろ過して該大麦玄麦アルカリ抽出液の液体分を得、該抽出液を凍結乾燥に付した。
[Brown alkali extracted fraction powder]
1 L of a 2% Ca (OH) 2 aqueous solution was added to 100 g of barley brown barley crushed with a mill, and the mixture was stirred and extracted at room temperature for 6 hours, and then the pH of the extract was adjusted to 7.0 using HCL. Subsequently, the mixture was filtered with 4C filter paper manufactured by ADVANTEC to obtain a liquid content of the barley brown barley alkaline extract, and the extract was freeze-dried.
〈実験試料の調製、実験方法、及び結果〉
１．実験試料
1-1 サンプル調製
1-1-1 血管新生阻害実験用
各試料を1000μgずつ秤量後、それぞれ別々に1mlの培地で溶解し、ろ過滅菌（0.22μm）後、10倍希釈（３回）を行い、表１（血管新生阻害効果評価試験サンプル内訳）に示す10μg/mlから1000μg/mlの濃度のサンプルを調製した。同様に表１に示すネガティブコントロール、ポジティブコントロールのサンプルを調製した。
２．実験方法、及び結果
ヒト血管内皮細胞と繊維芽細胞を最適濃度で共培養し、管腔形成初期段階の増殖状態にあるものに各サンプル（１-1-１、ネガティブコントロール、ポジティブコントロール）を添加し、11日間培養（4、7、9日後にサンプルを含む培地を交換）後、管腔形成をMouseanti-human CD31とGoat anti-mouse IgG AlkP Conjugateを用いて染色し、顕微鏡観察した。血管新生阻害効果について、形成された管腔様網目構造を評価した。
得られた結果を表２および図１ないし図３に示す。血管組織の写真をデジタルデータとして取り込み、ランダムに選択した数箇所の血管部分（黒色部分）の面積を測定することによって血管新生阻害の効果を求めた。即ち表２のAREAの欄の数値が小さいほど血管新生阻害の効果が高いサンプルであることを示している。
<Preparation of experimental samples, experimental methods, and results>
1. Experimental sample
1-1 Sample preparation
1-1-1 For angiogenesis inhibition experiment Each sample is weighed 1000 μg, dissolved separately in 1 ml medium, sterilized by filtration (0.22 μm), diluted 10 times (3 times), and Table 1 (Vessels) A sample having a concentration of 10 μg / ml to 1000 μg / ml as shown in the Breakdown of Newborn Inhibitory Effect Evaluation Test Sample) was prepared. Similarly, negative control and positive control samples shown in Table 1 were prepared.
2. Experimental methods and results Human vascular endothelial cells and fibroblasts were co-cultured at the optimal concentration, and each sample (1-1-1, negative control, positive control) was added to those in the proliferative state at the initial stage of tube formation. Then, after culturing for 11 days (the medium containing the sample was changed after 4, 7, and 9 days), tube formation was stained with Mouseanti-human CD31 and Goat anti-mouse IgG AlkP Conjugate and observed under a microscope. The formed lumen-like network structure was evaluated for the angiogenesis inhibitory effect.
The obtained results are shown in Table 2 and FIGS. The effect of inhibiting angiogenesis was determined by taking photographs of vascular tissues as digital data and measuring the areas of several randomly selected blood vessel portions (black portions). That is, the smaller the numerical value in the AREA column in Table 2, the higher the effect of inhibiting angiogenesis.
玄麦エタノール抽出画分に明らかな血管新生阻害の効果が見られた。 An obvious angiogenesis-inhibiting effect was observed in the extract of brown wheat ethanol.
実験２:
血管新生阻害実験
〈サンプル名称〉
表３に示すとおり。
Experiment 2:
Angiogenesis inhibition experiment <sample name>
As shown in Table 3.
血管新生阻害実験に用いたサンプル（１）〜（９）の調製法
本件に用いたサンプルについては、他の実験との兼ね合いがあり、粉末化したサンプルを再溶解して実験に用いているが、液状のまま、実験に用いても何ら問題はない。なお、下記したように粉末化する際に、賦形材としてエキスと等量のデキストリンを添加したものもある。なおデキストリン含量は重量パーセント濃度 (W/W)である。
Preparation method of samples (1) to (9) used in the angiogenesis inhibition experiment The sample used in this case has a balance with other experiments, and the powdered sample is redissolved and used in the experiment. There is no problem even if it is used in the experiment in the liquid state. In addition, when powdered as described below, there is also a product added with an equivalent amount of dextrin as an extractant. The dextrin content is weight percent concentration (W / W).
（１）［玄麦エタノール抽出画分粉末］
前記段落００３６を参照。
(1) [Brown ethanol extraction fraction powder]
See paragraph 0036 above.
（２）［玄麦アルカリ抽出画分粉末］
前記段落００３７を参照。
(2) [Brown wheat alkali extract fraction powder]
See paragraph 0037 above.
［実験試料の調製、実験方法、及び結果］
１．実験試料
1-1 サンプル調製
1-1-1 血管新生阻害実験用
各試料を1000μgずつ秤量後、それぞれ別々に1mlの培地で溶解し、ろ過滅菌（0.22μm）後、10倍希釈（３回）を行い、10μg/mlから1000μg/mlの濃度のサンプルを調製した。
[Preparation of experimental samples, experimental methods, and results]
1. Experimental sample
1-1 Sample preparation
1-1-1 For angiogenesis inhibition experiment Each sample is weighed in 1000μg, dissolved separately in 1ml medium, sterilized by filtration (0.22μm), diluted 10 times (3 times), from 10μg / ml A sample with a concentration of 1000 μg / ml was prepared.
２．実験方法及び結果
ヒト血管内皮細胞と繊維芽細胞を最適濃度で共培養し、管腔形成初期段階の増殖状態にあるものに各サンプルを添加し、11日間培養（4、7、9日後にサンプルを含む培地を交換）後、管腔形成をMouse anti-human CD31とGoat anti-mouse IgG AlkP Conjugateを用いて染色後、顕微鏡観察した。評価基準として、管腔形成を促進するVEGF-Aを10ng/ml、管腔形成を阻害するSuraminを50μMを同様に添加し、controlは無添加とした。血管新生阻害効果について、形成された管腔様網目構造を評価した。
方法：クラボウ社製のキットにより測定した。4つのポイントにおける管腔形成状態（面積、長さ、枝分れの数）を観察した。血管新生因子であるVEGFと血管新生抑制剤であるSuraminを共存させた系を対照とし、VEGFと各サンプル共存下の管腔形成状態を比較した。
（Suraminとサンプルの血管新生阻害活性を比較）
・サンプル添加濃度； 10、100、1000μｇ/ｍＬ
（Suraminは全て一定濃度；50μM）
結果：得られた結果を表３（血管新生阻害効果の数値データ）および図４に示した。
2. Experimental methods and results Human vascular endothelial cells and fibroblasts were co-cultured at optimal concentrations, each sample was added to the proliferating state at the initial stage of lumen formation, and cultured for 11 days (samples after 4, 7 and 9 days) After the medium containing the medium was exchanged), tube formation was stained with Mouse anti-human CD31 and Goat anti-mouse IgG AlkP Conjugate and then observed under a microscope. As evaluation criteria, 10 ng / ml of VEGF-A that promotes tube formation, 50 μM of Suramin that inhibits tube formation were similarly added, and control was not added. The formed lumen-like network structure was evaluated for the angiogenesis inhibitory effect.
Method: Measured with a kit manufactured by Kurabo Industries. The lumen formation state (area, length, number of branches) at four points was observed. Using a system in which VEGF as an angiogenic factor and Suramin as an angiogenesis inhibitor coexist as a control, the luminal formation state in the presence of VEGF and each sample was compared.
(Comparison of angiogenesis inhibitory activity of Suramin and sample)
Sample addition concentration: 10, 100, 1000 μg / mL
(Suramin is all constant concentration; 50μM)
Results: The results obtained are shown in Table 3 (numerical data on the angiogenesis inhibitory effect) and FIG.
上記表３および図４の結果より、玄麦エタノール抽出物は、10μg/ml、100μg/ml、1000μg/mlのすべてにおいて有意に管腔形成を阻害し、玄麦アルカリ抽出物の100μgは完全に管腔形成を阻害した。 From the results shown in Table 3 and FIG. 4, the barley ethanol extract significantly inhibited tube formation at all of 10 μg / ml, 100 μg / ml, and 1000 μg / ml, and 100 μg of the barley alkaline extract was completely luminal. Inhibited formation.
本発明の組成物は、有史以前から人類に欠かせない穀類で、日本の古い医学書にも記載されているなど、健康に良い食品として親しまれてきたイネ科植物である大麦由来の活性成分に基づく血管新生阻害を応用するものであり、機能性食品素材としての利用可能性が高い。 The composition of the present invention is an active ingredient derived from barley, which is a gramineous plant that has been loved as a healthy food, such as cereals indispensable for human beings from prehistoric times, as described in old Japanese medical books, etc. Is applied to inhibit angiogenesis based on the above, and is highly available as a functional food material.
Claims (8)
The composition for inhibiting angiogenesis according to claim 6, wherein the feed is a feed for livestock, poultry or pets for inhibiting angiogenesis.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005277652A JP4873605B2 (en) | 2005-09-26 | 2005-09-26 | A composition having an angiogenesis-inhibiting action comprising a cereal-derived ingredient as an active ingredient |
| US12/088,186 US20090263356A1 (en) | 2005-09-26 | 2006-09-26 | Anti-angiogenic composition comprising grain-derived component as active ingredient |
| PCT/JP2006/319016 WO2007034958A1 (en) | 2005-09-26 | 2006-09-26 | Anti-angiogenic composition comprising grain-derived component as active ingredient |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005277652A JP4873605B2 (en) | 2005-09-26 | 2005-09-26 | A composition having an angiogenesis-inhibiting action comprising a cereal-derived ingredient as an active ingredient |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007084503A true JP2007084503A (en) | 2007-04-05 |
| JP4873605B2 JP4873605B2 (en) | 2012-02-08 |
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| JP2005277652A Active JP4873605B2 (en) | 2005-09-26 | 2005-09-26 | A composition having an angiogenesis-inhibiting action comprising a cereal-derived ingredient as an active ingredient |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008143827A (en) * | 2006-12-08 | 2008-06-26 | Nippon Menaade Keshohin Kk | Skin care preparation, skin-lightening agent and composition for internal use |
| JP2016539943A (en) * | 2013-11-25 | 2016-12-22 | ユニヴァーシティ−インダストリー コーオペレイション グループ オブ キュン ヒー ユニヴァーシティ | Composition for preventing or treating growth disorders containing malt extract |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08301781A (en) * | 1995-05-10 | 1996-11-19 | Kureha Chem Ind Co Ltd | Hsp 47 synthesis suppressing agent |
| WO2003084302A2 (en) * | 2002-06-25 | 2003-10-16 | Shiseido Co Ltd | Anti-aging agent |
-
2005
- 2005-09-26 JP JP2005277652A patent/JP4873605B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH08301781A (en) * | 1995-05-10 | 1996-11-19 | Kureha Chem Ind Co Ltd | Hsp 47 synthesis suppressing agent |
| WO2003084302A2 (en) * | 2002-06-25 | 2003-10-16 | Shiseido Co Ltd | Anti-aging agent |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008143827A (en) * | 2006-12-08 | 2008-06-26 | Nippon Menaade Keshohin Kk | Skin care preparation, skin-lightening agent and composition for internal use |
| JP2016539943A (en) * | 2013-11-25 | 2016-12-22 | ユニヴァーシティ−インダストリー コーオペレイション グループ オブ キュン ヒー ユニヴァーシティ | Composition for preventing or treating growth disorders containing malt extract |
| US11324795B2 (en) | 2013-11-25 | 2022-05-10 | University-Industry Cooperation Group Of Kyung Hee University | Composition comprising Hordeum vulgare extract for preventing or treating short stature |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4873605B2 (en) | 2012-02-08 |
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