JP2021136983A - Nitric oxide production promoter and use thereof - Google Patents
Nitric oxide production promoter and use thereof Download PDFInfo
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- JP2021136983A JP2021136983A JP2020056840A JP2020056840A JP2021136983A JP 2021136983 A JP2021136983 A JP 2021136983A JP 2020056840 A JP2020056840 A JP 2020056840A JP 2020056840 A JP2020056840 A JP 2020056840A JP 2021136983 A JP2021136983 A JP 2021136983A
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Abstract
Description
本発明は、特定の植物を原料として使用した一酸化窒素（ＮＯ）産生促進剤及びその利用に関するものである。より詳細には、フトモモ科ギョリュウバイ属に属するマヌカの葉の抽出物を有効成分として含有してなることを特徴とする血管内皮細胞でのＮＯ産生促進剤、及び、該剤を含有してなることを特徴とする血管内皮機能を改善するための経口組成物に関する。 The present invention relates to a nitric oxide (NO) production promoter using a specific plant as a raw material and its use. More specifically, it contains a NO production promoter in vascular endothelial cells, which comprises an extract of Manuka leaves belonging to the genus Manuka of the Myrtaceae family as an active ingredient, and the agent. The present invention relates to an oral composition for improving vascular endothelial function.
血管内皮は血管の拡張及び／又は収縮、血管平滑筋細胞の増殖及び／又は抗増殖、血液凝固及び／又は抗凝固、血管の炎症及び／又は抗炎症、酸化及び／又は抗酸化等の様々な機能に影響を及ぼすことが知られている。そのため、血管内皮機能の低下は、糖尿病、高脂血症、高血圧、肥満等の原因となり、動脈硬化の初期症状とされている。更に、血管内皮機能の低下は、運動不足、塩分の過剰摂、喫煙取等によっても引き起こされるため、日常生活における血管内皮機能の維持・改善が重要である。 The vascular endothelium has a variety of vasodilation and / or contraction, vascular smooth muscle cell proliferation and / or antiproliferation, blood coagulation and / or anticoagulation, vascular inflammation and / or anti-inflammatory, oxidation and / or antioxidation, etc. It is known to affect function. Therefore, a decrease in vascular endothelial function causes diabetes, hyperlipidemia, hypertension, obesity, etc., and is regarded as an initial symptom of arteriosclerosis. Furthermore, since the decrease in vascular endothelial function is also caused by lack of exercise, excessive salt intake, smoking, etc., it is important to maintain and improve vascular endothelial function in daily life.
ＮＯは、ＮＯ合成酵素（ＮＯＳ）によりアルギニンから産生される。ＮＯＳには、神経型一酸化窒素合成酵素（ｎＮＯＳ）、誘導型一酸化窒素合成酵素（ｉＮＯＳ）及び血管内皮型一酸化窒素合成酵素（ｅＮＯＳ）の異なる３種のアイソフォームが存在する（非特許文献１）。ｎＮＯＳは、カルシウム依存性の酵素であり、脳においてシナプス可塑性の調節に関与している。ｉＮＯＳは、カルシウム非依存性の酵素であり、炎症やストレスにより強く誘導され、主に免疫機能に関与している。ｉＮＯＳによる過剰なＮＯ産生は、敗血症や関節リウマチの原因となる。ｅＮＯＳは、カルシウム依存性の酵素であり、血管拡張や血栓形成の抑制に関与している。 NO is produced from arginine by NO synthase (NOS). There are three different isoforms of NOS: neural nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), and vascular endothelial nitric oxide synthase (eNOS) (non-patentable). Document 1). nNOS is a calcium-dependent enzyme involved in the regulation of synaptic plasticity in the brain. iNOS is a calcium-independent enzyme that is strongly induced by inflammation and stress and is mainly involved in immune function. Excessive NO production by iNOS causes sepsis and rheumatoid arthritis. eNOS is a calcium-dependent enzyme involved in the suppression of vasodilation and thrombus formation.
血管内皮細胞におけるＮＯ産生の低下は、骨格筋でのエネルギー消費を抑制し、肥満や糖尿病の進行を誘導することが報告されている（非特許文献２）。ＮＯによる血管拡張以外の作用は、血管壁への単球・マクロファージの結合の抑制、血小板凝集抑制作用、血小板の接着・凝集の阻害による血栓形成の抑制等がある。血管内皮細胞から放出される他の血管拡張因子として、内皮由来血管過分極因子、プロスタグランジンＩ２等があり、血管収縮因子として、エンドセリン、トロンボキサンＡ２、アンジオテンシンＩＩ等の様々な生理活性物質が産生・分泌されることが明らかとなっている。これらの因子のバランスにより血管機能を調節・維持している。 It has been reported that a decrease in NO production in vascular endothelial cells suppresses energy consumption in skeletal muscle and induces the progression of obesity and diabetes (Non-Patent Document 2). Actions other than vasodilation by NO include suppression of monocyte / macrophage binding to the blood vessel wall, platelet aggregation inhibitory action, and inhibition of thrombus formation by inhibition of platelet adhesion / aggregation. Other vasodilators released from vascular endothelial cells include endothelium-derived vascular hyperpolarizing factor, prostaglandin I2, and various vasoconstrictor factors such as endothelin, thromboxane A2, and angiotensin II. It has been clarified that it is produced and secreted. The balance of these factors regulates and maintains vascular function.
後述するマヌカについては次のようなことが知られている。すなわち、マヌカは古くからニュージーランドの先住民マオリ族によって珍重されてきた薬木であり、その種子、樹皮、葉などは生薬として多岐にわたり利用されてきた（非特許文献３）。又、マヌカの花の蜜から採取されたマヌカハニーには、メチルグリオキサールが含まれ、抗菌作用があることが報告されている（非特許文献４）。その他に、歯周炎治療用剤（特許文献１）が提案されている。しかしながら、マヌカの葉に含まれる成分を経口的に摂取することにより、血管内皮細胞におけるＮＯ産生を促進する知見は見当たらない。 The following is known about Manuka, which will be described later. That is, Manuka is a medicinal tree that has been prized by the Maori tribe of New Zealand for a long time, and its seeds, bark, leaves, etc. have been widely used as crude drugs (Non-Patent Document 3). In addition, it has been reported that Manuka honey collected from the nectar of Manuka flowers contains methylglyoxal and has an antibacterial effect (Non-Patent Document 4). In addition, an agent for treating periodontitis (Patent Document 1) has been proposed. However, there is no finding that oral ingestion of the components contained in Manuka leaves promotes NO production in vascular endothelial cells.
かかる現状に鑑み、本発明は、血管内皮細胞でのＮＯ産生を促進するための、安全かつ安定な新規素材を開発するとともに、これを産業上有効活用できる態様の組成物を提供することを課題とした。 In view of this situation, it is an object of the present invention to develop a safe and stable new material for promoting NO production in vascular endothelial cells, and to provide a composition in a mode in which it can be effectively utilized industrially. And said.
前記課題を解決するために、本発明者らは、血管内皮細胞におけるＮＯ産生を促進するための素材について鋭意検討を重ねた結果、意外にもマヌカの葉が極めて有効であり、これらの植物にはヒトや動物のＮＯ産生を顕著に促進し得る成分が含まれており、これらの併用はより一層顕著に血管内皮細胞でのＮＯ産生を促進すること、更に、これを飲食品、医薬品、医薬部外品、飼料等の分野において有効利用できることを見出し、本発明を完成するに至った。 In order to solve the above-mentioned problems, the present inventors have conducted extensive studies on materials for promoting NO production in vascular endothelial cells, and as a result, surprisingly, Manuka leaves are extremely effective for these plants. Contains components that can significantly promote NO production in humans and animals, and their combined use further significantly promotes NO production in vascular endothelial cells, which can be used in foods and drinks, pharmaceuticals, and pharmaceuticals. We have found that it can be effectively used in the fields of external products, feeds, etc., and have completed the present invention.
すなわち、本発明によれば、フトモモ科ギョリュウバイ属（Ｌｅｐｔｏｓｐｅｒｍｕｍ）に属するマヌカ（Ｌｅｐｔｏｓｐｅｒｍｕｍ ｓｃｏｐａｒｉｕｍ）の葉の抽出物を有効成分として含有してなることを特徴とするＮＯ産生促進剤が提供される。この水性成分は、前記マヌカの葉を水及び／又は低級アルコールで抽出処理して得られる抽出物であることが望ましい。 That is, according to the present invention, there is provided a NO production promoter comprising an extract of leaves of Manuka (Leptospermum scorporium) belonging to the genus Manuka (Leptosperum) of the family Myrtaceae as an active ingredient. The aqueous component is preferably an extract obtained by extracting the leaves of Manuka with water and / or lower alcohol.
前述のように処理して得られる抽出物は、量的な差はあるものの多種多様な成分を含有する複雑な組成物であり、レプトスペリン、β−ｔｒｉｋｅｔｏｎｅ、ｔｅｒｐｉｎｅｎ−４−ｏｌ、１，８−ｃｉｎｅｏｌｅ、ｐｔｅｒｉｄｉｎｅｄｉｏｎｅ、３，６，７−ｔｒｉｍｅｔｈｙｌｌｕｍａｚｉｎｅ、ポリフェノール類、各種水溶性成分（多糖、オリゴ糖、単糖、蛋白、ペプチド、アミノ酸、これらの複合体など）を含んでいる。 The extracts obtained by the treatment as described above are complex compositions containing a wide variety of components, although there are quantitative differences, and are leptosperin, β-triketone, terpinen-4-ol, 1,8. It contains -cineole, pteridinedione, 3,6,7-trimethyllumazine, polyphenols, and various water-soluble components (polysaccharides, oligosaccharides, monosaccharides, proteins, peptides, amino acids, complexes thereof, etc.).
本発明の前記ＮＯ産生促進剤は、血管内皮細胞においてＮＯ産生を促進するものであることを特徴とする。 The NO production promoter of the present invention is characterized in that it promotes NO production in vascular endothelial cells.
本発明の他の特徴は、前記のＮＯ産生促進剤を含有してなる経口組成物が提供される点にある。この経口組成物の態様は飲食品であることが望ましい。 Another feature of the present invention is that an oral composition containing the above-mentioned NO production promoter is provided. It is desirable that the aspect of this oral composition is food or drink.
又、本発明によれば、前記ＮＯ産生促進剤を含有してなることを特徴とする抗疲労のための経口組成物あるいは飲食品が提供される。 Further, according to the present invention, there is provided an oral composition or a food or drink for anti-fatigue, which is characterized by containing the NO production promoter.
本発明のさらなる他の特徴は、フトモモ科ギョリュウバイ属に属するマヌカの葉を水及び／又は低級アルコールで抽出したエキスを有効成分として含有せしめるＮＯ産生促進剤の製造方法にある。 A further feature of the present invention is a method for producing a NO production promoter containing an extract of Manuka leaves belonging to the genus Manuka of the Myrtaceae family with water and / or lower alcohol as an active ingredient.
本発明のさらなる他の特徴は、血管内皮細胞でのＮＯ産生を促進するために前記ＮＯ産生促進剤あるいは経口組成物を経口投与又は摂取する方法にある。 Yet another feature of the present invention is a method of orally administering or ingesting the NO production promoter or oral composition in order to promote NO production in vascular endothelial cells.
本発明に係るマヌカの葉の抽出物は、品質安定性に優れ、血管内皮細胞におけるＮＯ産生を促進することにより、レイノー症、動脈硬化症、バージャー病、高血圧症、脳血栓、脳梗塞、心筋梗塞、充血、鬱血、出血、貧血、認知症、免疫力の低下、脱毛症、倦怠感、疲労、筋肉痛、疲れ目、むくみ、肩こり、腰痛、皮膚のかゆみ、くま、くすみ、しもやけ、凍傷、シワ、肌の弾力低下、歯周病等の血管機能の障害により引き起される症状を予防及び／又は改善する効果、及び、発毛、育毛、養毛、滋養強壮、美肌等の効果を奏する。かかる効果は、前記加工物を有効成分として含有してなるＮＯ産生促進剤を経口的に摂取又は投与することによって顕著に発現される。したがって、本発明によれば、マヌカの葉の抽出物を有効成分として含有してなる経口用組成物が提供され、これを血管内皮細胞でのＮＯ産生の低下により引き起こされる諸症状を予防及び／又は改善するための飲食品、医薬品、医薬部外品、飼料等として有効利用することができる。 The manuka leaf extract according to the present invention has excellent quality stability and promotes NO production in vascular endothelial cells, thereby promoting Reynaud's disease, arteriosclerosis, Buerger's disease, hypertension, cerebral thrombosis, cerebral infarction, and myocardial infarction. , Congestion, depression, bleeding, anemia, dementia, weakened immunity, alopecia, malaise, fatigue, muscle pain, tired eyes, swelling, stiff shoulders, lower back pain, itchy skin, dark circles, dullness, chilblains, frosts, wrinkles It has the effect of preventing and / or ameliorating the symptoms caused by impaired vascular function such as decreased skin elasticity and periodontal disease, and the effects of hair growth, hair growth, hair nourishment, nourishing tonic, and beautiful skin. Such an effect is remarkably exhibited by orally ingesting or administering a NO production promoter containing the processed product as an active ingredient. Therefore, according to the present invention, an oral composition comprising an extract of Manuka leaf as an active ingredient is provided, which prevents various symptoms caused by a decrease in NO production in vascular endothelial cells and /. Alternatively, it can be effectively used as food and drink, pharmaceuticals, quasi-drugs, feeds, etc. for improvement.
以下に本発明を詳細に説明する。まず、本発明のＮＯ産生促進剤は、ヒトや動物の血管内皮細胞でのＮＯ産生を促進する機能を有するものであり、フトモモ科ギョリュウバイ属（Ｌｅｐｔｏｓｐｅｒｍｕｍ）に属するマヌカ（Ｌｅｐｔｏｓｐｅｒｍｕｍ ｓｃｏｐａｒｉｕｍ）の葉の抽出物を有効成分として含有してなることを特徴とする。 The present invention will be described in detail below. First, the NO production promoter of the present invention has a function of promoting NO production in human or animal vascular endothelial cells, and extracts leaves of Manuka (Leptospermum scoparium) belonging to the genus Manuka (Leptosperum) of the family Myrtaceae. It is characterized by containing a substance as an active ingredient.
前記マヌカの葉の抽出物は任意の方法で製造することができるが、水及び／又は低級アルコールを用いて抽出処理するのが好ましい。低級アルコールは、その炭素数が大きくなると脱脂粕中の油性物質が抽出される傾向が大きくなるため、炭素数が５程度までのものが望ましく、メタノール、エタノール、ノルマルプロパノール、イソプロパノール、ノルマルブタノール、イソブタノール等を例示できる。炭素数が大きい低級アルコールを使用する場合は、脱脂粕中の油性成分の抽出を抑制するために含水率を高めるのがよい。例えば、ｎ−プロパノールの場合の含水率は約２０質量％〜約５０質量％とし、ｎ−ブタノールの場合の含水率は約４０質量％〜約７０質量％とする。望ましい抽出溶媒は水、メタノール及びエタノール、及び、これらの含水アルコール（含水率：０〜１００質量％）である。 The Manuka leaf extract can be produced by any method, but it is preferably treated with water and / or lower alcohol. As the carbon number of the lower alcohol increases, the oily substance in the defatted lees tends to be extracted. Therefore, it is desirable that the lower alcohol has a carbon number of up to about 5, methanol, ethanol, normal propanol, isopropanol, normal butanol, and iso. Butanol and the like can be exemplified. When a lower alcohol having a large number of carbon atoms is used, it is preferable to increase the water content in order to suppress the extraction of oily components in the degreasing lees. For example, the water content in the case of n-propanol is about 20% by mass to about 50% by mass, and the water content in the case of n-butanol is about 40% by mass to about 70% by mass. Desirable extraction solvents are water, methanol and ethanol, and their hydrous alcohols (moisture content: 0-100% by mass).
マヌカの葉を抽出するには、マヌカの葉１質量部に対して前記抽出溶媒を約１質量倍〜約３０質量倍加え、常圧下又は１〜５気圧の加圧下、常温ないしは約１２０℃で、約１０分〜約３時間、必要に応じて撹拌して混合後、常温に冷却して濾過し、濾液を減圧乾燥、噴霧乾燥、凍結乾燥等の適当な手段により濃縮、乾燥する。尚、乾燥物は適宜に粉砕処理してもよい。このようにして本発明に係るマヌカの葉の抽出物である淡黄色ないし黄赤色の固体を得ることができる。前記抽出方法は、一旦抽出処理した抽出残渣を繰り返し抽出処理したり、１〜３気圧の加圧下、約１００℃〜約１３０℃で行うことが望ましい。これにより本発明に係る抽出物の収量が増える。この抽出物はポリフェノール、サポニン等を含む。 To extract manuka leaves, add the extraction solvent about 1 to about 30 times by mass to 1 part by mass of manuka leaves, and under normal pressure or pressurization of 1 to 5 atm, at room temperature or about 120 ° C. , If necessary, stir and mix for about 10 minutes to about 3 hours, cool to room temperature, filter, and concentrate and dry the filtrate by appropriate means such as vacuum drying, spray drying, and freeze drying. The dried product may be appropriately pulverized. In this way, a pale yellow to yellow-red solid, which is an extract of Manuka leaves according to the present invention, can be obtained. It is desirable that the extraction method is carried out by repeatedly extracting the extraction residue once extracted, or by performing the extraction treatment at about 100 ° C. to about 130 ° C. under pressure of 1 to 3 atm. This increases the yield of the extract according to the present invention. This extract contains polyphenols, saponins and the like.
本発明のＮＯ産生促進剤は、その有効成分としての前記抽出物を固体状、ペースト状又は液体状の形態となし、これをそのままＮＯ産生促進剤としてよいが、必要に応じて本発明のＮＯ産生促進剤が利用される用途における公知の添加物を併用して、常法により含有せしめて組成物として調製することもできる。ここで、公知の添加物は経口摂取するために通常利用されるものが望ましく、例えば、賦形剤、結合剤、崩壊剤、滑沢剤、湿潤剤、流動化剤、保存剤、界面活性剤、安定剤、希釈剤、溶解剤、等張化剤、殺菌剤、防腐剤、矯味剤、矯臭剤、着色剤、香料等の添加物質を使用でき、又、ＮＯ産生促進効果を有する既知成分やその含有素材を併用してもよい。 The NO production promoter of the present invention may take the extract as an active ingredient in a solid, paste or liquid form and use it as it is as a NO production promoter, but the NO of the present invention may be used as it is. It is also possible to prepare the composition by adding it in combination with a known additive in the application in which the production promoter is used and by a conventional method. Here, it is desirable that known additives are usually used for oral ingestion, for example, excipients, binders, disintegrants, lubricants, wetting agents, fluidizing agents, preservatives, surfactants. , Stabilizers, diluents, solubilizers, isotonic agents, bactericides, preservatives, flavoring agents, odorants, coloring agents, fragrances and other additive substances can be used, and known ingredients having a NO production promoting effect The contained material may be used together.
血管内皮細胞でのＮＯ産生促進作用が既知の成分や素材としては、前記のもののほか黒酢、グルタチオン、イチョウ葉エキス、ヘスペリジン、シトルリン、ルチン、ショウガ、黒ショウガ、ヒハツ、ブドウ茎抽出物、ブドウ果皮抽出物、トランスレスベラトロール、リンゴ果皮抽出物、黒大豆ポリフェノール、ココアポリフェノール、ピクノジェノール、フラバンジェノール、ケイヒ、高麗人参、卵白ペプチド、鶏、豚又は魚由来のコラーゲンペプチド、ツバキ種子抽出物、アカショウマ根茎抽出物等を例示できる。尚、本発明はこれらの例示によって何ら限定されるものではない。 In addition to the above, other components and materials known to promote NO production in vascular endothelial cells include black vinegar, glutathione, ginkgo biloba extract, hesperidin, citrulin, rutin, ginger, black ginger, hihatsu, grape stalk extract, and grapes. Peel extract, transresveratrol, apple peel extract, black soybean polyphenol, cocoa polyphenol, pycnogenol, flavangenol, keihi, ginger, egg white peptide, chicken, pig or fish-derived collagen peptide, camellia seed extract, Examples include red ginger rhizome extract and the like. The present invention is not limited to these examples.
本発明においては、前述したＮＯ産生促進剤をそのままの形態で飲食品、医薬品、医薬部外品、飼料、その他産業分野の様々な製品として利用することができ、あるいは該各種製品の配合原料の一部として使用する態様でも利用できる。とりわけＮＯ産生を促進するための経口組成物となすことが好ましく、この経口組成物の最も好適な態様は飲食品である。この例を以下に述べるが、本発明はこれにより限定されるものではない。 In the present invention, the above-mentioned NO production promoter can be used as it is as various products in foods and drinks, pharmaceuticals, quasi-drugs, feeds, and other industrial fields, or can be used as a compounding raw material for the various products. It can also be used as a part. In particular, it is preferably an oral composition for promoting NO production, and the most preferable aspect of this oral composition is food and drink. This example will be described below, but the present invention is not limited thereto.
本発明のＮＯ産生促進剤を経口組成物とする場合の形態は、顆粒剤、錠剤、カプセル剤、液剤等の経口用製剤となすことが可能である。かかる製剤組成物における前記のマヌカの葉由来抽出物の含有量は、併用原料の種類や含有量等により一律に規定し難いが、各々概ね０．００１質量％〜９０質量％程度、より望ましくは約０．０１質量％〜約７０質量％である。前記含有量が約０．００１質量％を下回ると本発明の所望効果が認められなくなり、約９０質量％を超えると実用的な製剤組成物を調製することが難しくなる。本発明のＮＯ産生促進剤は、これを望ましくは経口的に摂取又は投与する態様で使用する。経口摂取又は投与する場合の本発明のＮＯ産生促進剤の好適な量の目安は、該剤に含まれる前記水性成分ベースあるいは前記抽出物ベースで、ヒト成人１日あたり約１０ｍｇ〜約１，０００ｍｇ、望ましくは約３０ｍｇ〜約５００ｍｇ、更に望ましくは約５０ｍｇ〜約３００ｍｇである。 When the NO production promoter of the present invention is used as an oral composition, it can be an oral preparation such as granules, tablets, capsules, and liquids. The content of the Manuka leaf-derived extract in such a pharmaceutical composition is difficult to uniformly define depending on the type and content of the combined raw materials, but each is approximately 0.001% by mass to 90% by mass, more preferably. It is about 0.01% by mass to about 70% by mass. If the content is less than about 0.001% by mass, the desired effect of the present invention is not recognized, and if it exceeds about 90% by mass, it becomes difficult to prepare a practical pharmaceutical composition. The NO production promoter of the present invention is preferably used in a mode in which it is orally ingested or administered. A suitable amount of the NO production promoter of the present invention when ingested or administered is based on the aqueous component or the extract contained in the agent, and is about 10 mg to about 1,000 mg per day for a human adult. , Desirably from about 30 mg to about 500 mg, and more preferably from about 50 mg to about 300 mg.
本発明のＮＯ産生促進剤は、これ自体を飲食品、医薬品、飼料その他産業分野の様々な形態の製品とすることができ、あるいは、かかる製品の配合原料の一部とする態様でも利用することができる。実用的な用途としては飲食品がよい。 The NO production promoter of the present invention can be used as a product in various forms in food and drink, pharmaceuticals, feed and other industrial fields, or can be used as a part of a compounding raw material of such a product. Can be done. Food and drink are good for practical use.
飲食品の具体例として、野菜ジュース、果汁飲料、清涼飲料、茶等の飲料類、即席麺、スープ、ゼリー、プリン、ヨーグルト、ケーキプレミックス製品、菓子類、ふりかけ、味噌、醤油、ソース、ドレッシング、マヨネーズ、植物性クリーム、焼肉用たれや麺つゆ等の調味料、麺類、うどん、蕎麦、スパゲッティ、ハムやソーセージ等の畜肉魚肉加工食品、ハンバーグ、コロッケ、ふりかけ、佃煮、ジャム、牛乳、クリーム、バター、スプレッドやチーズ等の粉末状、固形状又は液状の乳製品、マーガリン、パン、ケーキ、クッキー、チョコレート、キャンディー、グミ、ガム、ゼリー等の各種一般加工食品のほか、粉末状、顆粒状、丸剤状、錠剤状、ソフトカプセル状、ハードカプセル状、ペースト状又は液体状の栄養補助食品、特定保健用食品、機能性表示食品、健康食品、濃厚流動食や嚥下障害用食品の治療食等を挙げることができる。 Specific examples of foods and drinks include vegetable juice, fruit juice beverages, soft drinks, tea and other beverages, instant noodles, soups, jellies, puddings, yogurts, cake premix products, confectionery, sprinkles, miso, soy sauce, sauces, and dressings. , Mayonnaise, vegetable cream, seasonings such as sauce for roasted meat and noodle soup, noodles, udon, soba, spaghetti, processed livestock fish such as ham and sausage, hamburger, croquette, sprinkle, boiled, jam, milk, cream, Powdered, solid or liquid dairy products such as butter, spreads and cheese, various general processed foods such as margarine, bread, cake, cookies, chocolate, candy, gummy, gum, jelly, as well as powdered, granular, Rounds, tablets, soft capsules, hard capsules, paste or liquid nutritional supplements, foods for specified health use, foods with functional claims, health foods, foods for concentrated liquid foods and foods for swallowing disorders, etc. be able to.
尚、本発明の飲食品においては、これがマヌカの葉の抽出物を有効成分として含有してなる旨、血管内皮細胞でのＮＯ産生を促進するためのものである旨のうち少なくとも１つの表示を付した態様とすることができる。 In the food and drink of the present invention, at least one indication that this contains an extract of Manuka leaf as an active ingredient and that it is for promoting NO production in vascular endothelial cells is indicated. It can be attached.
これらの飲食品を製造するには、本発明のＮＯ産生促進剤と公知の原材料を用い、あるいは公知の原材料の一部を前記のＮＯ産生促進剤で置き換え、常法によって製造すればよい。例えば、本発明のＮＯ産生促進剤を、必要に応じてグルコース（ブドウ糖）、デキストリン、乳糖、澱粉又はその加工物、セルロース粉末等の賦形剤、ビタミン、ミネラル、動植物や魚介類の油脂、たん白（動植物や酵母由来の蛋白質、その加水分解物等を含む）、糖質、色素、香料、酸化防止剤、界面活性剤、その他の食用添加物、各種栄養機能成分を含む粉末やエキス類等の食用素材とともに混合して粉末、顆粒、ペレット、錠剤等の形状に加工したり、常法により前記例の一般加工食品に加工処理したり、これらを混合した液状物をゼラチン、アルギン酸ナトリウム、カルボキシメチルセルロース等の被覆剤で被覆してカプセルに成形したり、飲料（ドリンク類）の形態に加工して、栄養補助食品や健康食品として利用することは好適である。とりわけ錠剤、カプセル剤やドリンク剤が望ましい。 In order to produce these foods and drinks, the NO production promoter of the present invention and known raw materials may be used, or a part of the known raw materials may be replaced with the NO production promoter and produced by a conventional method. For example, the NO production promoter of the present invention can be used as necessary for glucose (dextrin), dextrin, lactose, starch or processed products thereof, excipients such as cellulose powder, vitamins, minerals, fats and oils of animals, plants and seafood, and protein. White (including proteins derived from animals and plants and yeast, their hydrolyzates, etc.), sugars, pigments, fragrances, antioxidants, surfactants, other edible additives, powders and extracts containing various nutritional functional ingredients, etc. It can be mixed with the edible materials of the above and processed into powders, granules, pellets, tablets, etc., or processed into the general processed foods of the above examples by a conventional method, or the liquid material obtained by mixing these can be gelatin, sodium alginate, carboxy. It is suitable to coat it with a coating agent such as methylcellulose and form it into capsules, or process it into a beverage (drinks) form and use it as a dietary supplement or health food. Tablets, capsules and energy drinks are especially desirable.
かかる飲食品に配合する本発明のＮＯ産生促進剤の比率は、飲食品の形態、本発明のＮＯ産生促進剤中の前記抽出物（マヌカの葉の抽出物）の含量、他の配合原料の種類や成分や配合量等の違いにより一律に規定しがたいが、飲食品中の前記抽出物の含量が約０．０１質量％〜約９０質量％、より望ましくは約１質量％〜約５０質量％となるように、本発明のＮＯ産生促進剤をその他の飲食品製造用公知原料と適宜に組み合わせて処方を設計し、常法に従い目的とする飲食品を調製すればよい。本発明の飲食品は、ヒト成人の場合１日あたりの前記水性成分の摂取量の目安を約１０ｍｇ〜約１，０００ｍｇ、望ましくは約３０ｍｇ〜約５００ｍｇ、更に望ましくは約５０ｍｇ〜約３００ｍｇとして任意の方法、例えば、食事の摂取と同時又は前後に、経口摂取、経管投与等の方法で体内に取り込むことができる。 The ratio of the NO production promoter of the present invention to be blended in such foods and drinks is the form of the food and drink, the content of the extract (manuka leaf extract) in the NO production promoter of the present invention, and other compounding raw materials. Although it is difficult to specify uniformly due to differences in types, ingredients, blending amounts, etc., the content of the extract in food and drink is about 0.01% by mass to about 90% by mass, and more preferably about 1% by mass to about 50. A formulation may be designed by appropriately combining the NO production promoter of the present invention with other known raw materials for producing foods and drinks so as to have a mass% of mass, and the desired foods and drinks may be prepared according to a conventional method. In the case of a human adult, the food or drink of the present invention is arbitrary, with the standard intake of the aqueous component per day being about 10 mg to about 1,000 mg, preferably about 30 mg to about 500 mg, and more preferably about 50 mg to about 300 mg. For example, it can be taken into the body by a method such as oral ingestion or tube administration at the same time as or before or after ingestion of a meal.
本発明のＮＯ産生促進剤を用いる医薬品は、前記のＮＯ産生促進剤に本発明の趣旨に反しない公知の賦形剤や添加物を適宜に加え、常法により加工して錠剤、カプセル剤、顆粒剤、散剤、液剤等の製剤となすことができる。経口あるいは経腸投与して、ＮＯ産生の促進あるいは前記諸症状の予防又は治療のために適用する。本発明のＮＯ産生促進剤の配合量はその形態や前記医薬製剤の種類、形態、用法及び用量等により一律に設定し難いが、前記抽出物の含量として概ね０．００１質量％〜５０質量％である。経口投与する場合の摂取量はとくに限定されるものではないが、例えば、前記抽出物をベースにして、ヒト成人１日あたり約０．１ｍｇ〜約１，０００ｍｇ、望ましくは約１ｍｇ〜約５００ｍｇ、更に望ましくは約１０ｍｇ〜約３００ｍｇである。 The pharmaceutical product using the NO production promoter of the present invention is prepared by appropriately adding a known excipient or additive that does not contradict the gist of the present invention to the NO production promoter, and processing it by a conventional method into tablets, capsules, and the like. It can be made into a preparation such as a granule, a powder, or a liquid. It is orally or enterally administered to promote NO production or to prevent or treat the above-mentioned symptoms. It is difficult to uniformly set the blending amount of the NO production promoter of the present invention depending on the form, the type, form, usage, dose, etc. of the pharmaceutical preparation, but the content of the extract is approximately 0.001% by mass to 50% by mass. Is. The amount of intake when orally administered is not particularly limited, but for example, based on the extract, about 0.1 mg to about 1,000 mg, preferably about 1 mg to about 500 mg, per day for a human adult. More preferably, it is about 10 mg to about 300 mg.
又、本発明のＮＯ産生促進剤をペットフードや家畜用飼料に適用するには、前記飲食品の場合と同様に、公知の各種飼料や飲用水に配合したり、公知の原材料、添加物とともに錠剤状、顆粒状、カプセル状等の製剤形態のものに加工することができる。これらの場合、本発明のＮＯ産生促進剤の配合量及び摂取量は、前記抽出物の含量として約０．０１質量％〜約９０質量％、より望ましくは約１質量％〜約５０質量％であり、１日あたりの摂取量の目安は、前記抽出物を基準として、適用動物の体重（ｋｇ）あたり約０．１ｍｇ〜約１００ｍｇ、より望ましくは約０．５ｍｇ〜約５０ｍｇである。 Further, in order to apply the NO production promoter of the present invention to pet food and livestock feed, as in the case of the above-mentioned food and drink, it may be blended with various known feeds and drinking water, or together with known raw materials and additives. It can be processed into a pharmaceutical form such as a tablet, a granule, or a capsule. In these cases, the blending amount and intake amount of the NO production promoter of the present invention are about 0.01% by mass to about 90% by mass, and more preferably about 1% by mass to about 50% by mass as the content of the extract. The guideline for daily intake is about 0.1 mg to about 100 mg, and more preferably about 0.5 mg to about 50 mg, per body weight (kg) of the applicable animal, based on the extract.
製造例１
ニュージーランド産マヌカ（Ｌｅｐｔｏｓｐｅｒｍｕｍ ｓｃｏｐａｒｉｕｍ）の乾燥葉を粗粉砕した。このマヌカ乾燥葉１Ｋｇをステンレス製抽出釜に仕込み、水９Ｌを加え、適宜に撹拌しながら７０℃で６時間抽出処理した。この後、不溶の残渣を濾別してエキス液を採取し、該エキス液を減圧濃縮、凍結乾燥及び粉砕処理に供して茶褐色のエキス末（試料Ｍ−１）を得た。Manufacturing example 1
Dried leaves of New Zealand Manuka (Leptospermum scoparium) were coarsely ground. 1 kg of dried Manuka leaves was placed in a stainless steel extraction kettle, 9 L of water was added, and extraction treatment was performed at 70 ° C. for 6 hours with appropriate stirring. Then, the insoluble residue was filtered off to collect an extract solution, and the extract solution was subjected to vacuum concentration, freeze-drying and pulverization treatment to obtain a brown extract powder (Sample M-1).
製造例２
製造例１に記載の方法で得た乾燥葉１００ｇに含水エタノール（含水率５０％）２５０ｍＬを加え、８０℃で１時間加熱還流した後、室温まで冷却し、濾過して濾液を分離した。この濾過残渣に再度含水エタノール（含水率５０％）２００ｍＬを加えて同様に加熱し、冷却後、濾過して濾液を採取した。両濾液を合わせて減圧下に濃縮し、凍結乾燥及び粉砕して、茶褐色のエキス末（試料Ｍ−２）を得た。Manufacturing example 2
250 mL of hydrous ethanol (water content 50%) was added to 100 g of the dried leaves obtained by the method described in Production Example 1, and the mixture was heated under reflux at 80 ° C. for 1 hour, cooled to room temperature, and filtered to separate the filtrate. 200 mL of hydrous ethanol (water content 50%) was added to the filtration residue again, the mixture was heated in the same manner, cooled, and then filtered to collect a filtrate. Both filtrates were combined and concentrated under reduced pressure, lyophilized and pulverized to obtain a brown extract powder (Sample M-2).
製造例３
製造例１に記載の方法で得た乾燥葉１Ｋｇをステンレス製抽出釜に仕込み、エタノール９Ｌを加え、適宜に撹拌しながら７０℃で６時間抽出処理した。この後、不溶の残渣を濾別してエキス液を採取し、該エキス液を減圧濃縮、凍結乾燥及び粉砕処理に供して茶褐色のエキス末（試料Ｍ−３）を得た。Manufacturing example 3
1 kg of dried leaves obtained by the method described in Production Example 1 was placed in a stainless steel extraction kettle, 9 L of ethanol was added, and extraction treatment was performed at 70 ° C. for 6 hours with appropriate stirring. Then, the insoluble residue was filtered off to collect an extract, and the extract was concentrated under reduced pressure, freeze-dried and pulverized to obtain a brown extract powder (Sample M-3).
試験例
前記製造例で得た各試料のＮＯ産生促進作用について以下に述べる方法で調べた。Test Example The NO production promoting action of each sample obtained in the above production example was investigated by the method described below.
試験例１：マヌカの葉由来抽出物によるウシ大動脈内皮細胞（ＢＡＥＣ）のＮＯ産生促進作用
動物細胞でのＮＯ産生促進作用を調べるため、ＢＡＥＣを使用した。ＢＡＥＣを９６ｗｅｌｌプレートに１×１０４個／ｗｅｌｌずつ播種し、３７℃で１日間培養した。その後、ＮＯ検出用蛍光プローブであるＤＡＦ−ＦＭ ＤＡを細胞に取り込ませ、試料Ｍ−１、Ｍ−２及びＭ−３を１０、２５、５０、１００μｇ／ｍＬで添加し、３７℃で２４時間インキュベートした。培養終了後、励起波長：４９０ｎｍ、蛍光波長：５２０ｎｍの蛍光強度を測定し、試料無添加の場合のＮＯ産生量を１としたときの相対値（活性）として、平均値±標準偏差（ｎ＝３）で表わした（表１）。Test Example 1: NO production-promoting effect of bovine aortic endothelial cells (BAEC) by manuka leaf-derived extract BAEC was used to investigate the NO production-promoting effect on animal cells. BAEC was seeded on 96-well plates at a rate of 1 × 10 4 cells / well and cultured at 37 ° C. for 1 day. Then, DAF-FM DA, which is a fluorescent probe for NO detection, was taken up into cells, and samples M-1, M-2 and M-3 were added at 10, 25, 50 and 100 μg / mL, and the temperature was 37 ° C. for 24 hours. Incubated. After completion of the culture, the fluorescence intensity at the excitation wavelength: 490 nm and the fluorescence wavelength: 520 nm was measured, and the relative value (activity) when the NO production amount when no sample was added was 1, the average value ± standard deviation (n =). It is represented by 3) (Table 1).
この結果を表１に示す。同表のデータから、本発明に係るマヌカの葉由来抽出物は濃度依存的にウシ大動脈内皮細胞のＮＯ産生促進作用を有することを確認した。 The results are shown in Table 1. From the data in the table, it was confirmed that the manuka leaf-derived extract according to the present invention has a concentration-dependent NO production-promoting effect on bovine aortic endothelial cells.
試験例２：マヌカの葉由来抽出物によるヒト臍帯静脈内皮細胞（ＨＵＶＥＣ）のＮＯ産生促進作用
ヒト細胞でのＮＯ産生促進作用を調べるため、ＨＵＶＥＣを用いた。ＨＵＶＥＣを９６ｗｅｌｌプレートに１×１０４個／ｗｅｌｌずつ播種し、３７℃で１日間培養した。その後、ＮＯ検出用蛍光プローブであるＤＡＦ−ＦＭ ＤＡを細胞に取り込ませ、試料Ｍ−１、Ｍ−２及びＭ−３を１０、２５、５０、１００μｇ／ｍＬで添加し、３７℃で２４時間インキュベートした。培養終了後、励起波長：４９０ｎｍ、蛍光波長：５２０ｎｍの蛍光強度を測定し、試料無添加の場合のＮＯ産生量を１としたときの相対値（活性）として、平均値±標準偏差（ｎ＝３）で表わした（表２）。Test Example 2: NO production promoting action of human umbilical vein endothelial cells (HUVEC) by manuka leaf-derived extract HUVEC was used to investigate the NO production promoting action in human cells. HUVEC was seeded on 96-well plates at a rate of 1 × 10 4 cells / well and cultured at 37 ° C. for 1 day. Then, DAF-FM DA, which is a fluorescent probe for NO detection, was taken up into cells, and samples M-1, M-2 and M-3 were added at 10, 25, 50 and 100 μg / mL, and the temperature was 37 ° C. for 24 hours. Incubated. After completion of the culture, the fluorescence intensity at the excitation wavelength: 490 nm and the fluorescence wavelength: 520 nm was measured, and the relative value (activity) when the NO production amount when no sample was added was 1, the average value ± standard deviation (n =). It is represented by 3) (Table 2).
この結果を表２に示す。同表のデータから、本発明に係るマヌカの葉由来抽出物はヒト臍帯静脈内皮細胞においても濃度依存的にＮＯ産生促進作用を有することを確認した。 The results are shown in Table 2. From the data in the table, it was confirmed that the manuka leaf-derived extract according to the present invention also has a concentration-dependent NO production-promoting effect on human umbilical vein endothelial cells.
試験例３：他の植物由来抽出物によるヒト臍帯静脈内皮細胞（ＨＵＶＥＣ）のＮＯ産生促進作用
本試験において、本発明のマヌカの葉由来抽出物と比較するＮＯ産生促進物として、ヒハツエキスパウダー（Ｔｉｅ２ヒハツエキスパウダーＭＦ、丸善製薬社製）（比較試料１とする。）、カシスポリフェノール（明治カシスポリフェノール（ＡＣ１０）、明治フードマテリア社製）（比較試料２とする。）及びヘスペリジン（αＧヘスペリジンＰＡ−Ｔ、東洋精糖社製）（比較試料３とする。）を用いた。ＮＯ産生量の測定は試験例２と同様の方法を用いて行い、試料を添加しない場合のＮＯ産生量を１としたときの相対値（活性）として、平均値±標準偏差（ｎ＝３）で表わした（表３）。Test Example 3: NO production promoting action of human umbilical vein endothelial cells (HUVEC) by other plant-derived extracts In this test, as a NO production promoting product compared with the manuka leaf-derived extract of the present invention, Hihatsu extract powder (Tie2). Hihatsu extract powder MF, manufactured by Maruzen Pharmaceuticals Co., Ltd. (referred to as comparative sample 1), cassis polyphenol (Meiji Cassis polyphenol (AC10), manufactured by Meiji Food Materia Co., Ltd.) (referred to as comparative sample 2) and hesperidin (αG hesperidin PA-T). , Toyo Seisakusho Co., Ltd.) (referred to as Comparative Sample 3) was used. The NO production amount was measured using the same method as in Test Example 2, and the relative value (activity) when the NO production amount when no sample was added was 1, the average value ± standard deviation (n = 3). It is represented by (Table 3).
この結果を表３に示す。同表のデータから、本発明に係るマヌカの葉由来抽出物はヒト臍帯静脈内皮細胞において他のＮＯ産生促進剤よりも顕著なＮＯ産生促進作用を有することを確認した。 The results are shown in Table 3. From the data in the table, it was confirmed that the manuka leaf-derived extract according to the present invention has a remarkable NO production-promoting effect on human umbilical vein endothelial cells as compared with other NO production-promoting agents.
試験例４：マウスにおけるＮＯ産生促進試験及び抗疲労試験
ＮＯ産生促進作用及び抗疲労作用を以下の方法で調べた。すなわち、６週齢ｄｄｙ系雄マウス（三協ラボサービス（株））を１週間予備飼育した後、１群６匹とし、蒸留水を投与する対照群及び試料Ｍ−１投与群に群分けした。共通飼料（日本クレア株式会社製、商品名ＣＥ−２）を自由摂取させて、それぞれの試料２００ｍｇ／ｋｇ体重／日を毎日経口投与し、全てのマウスに１週間３回の遊泳運動を実施させて４週間飼育した。飼育２週目にマウスの尾に２ｇの錘をつけ、水槽で遊泳させ、疲労困憊してマウスの頭頂部が水面下に沈み込むような遊泳運動が継続不能になるまでの時間（限界遊泳時間）を測定した。また、飼育終了後にマウスの血液を採取し、遠心分離して得た血漿中のＮＯをＮＯ２／ＮＯ３ Ａｓｓａｙ Ｋｉｔ−Ｃ ＩＩ（Ｃｏｌｏｒｉｍｅｔｒｉｃ）〜Ｇｒｉｅｓｓ Ｒｅａｇｅｎｔ Ｋｉｔ〜（同仁化学研究所製）を用いて測定した。血中ＮＯ濃度は対照群の値を１００としたときの相対値として、平均値±標準偏差で表わした（表４）。Test Example 4: NO production promoting test and anti-fatigue test in mice The NO production promoting action and anti-fatigue action were examined by the following methods. That is, 6-week-old dddy male mice (Sankyo Lab Service Co., Ltd.) were preliminarily bred for 1 week, and then 6 animals per group were divided into a control group to which distilled water was administered and a sample M-1 administration group. .. Free intake of common feed (manufactured by Nippon Claire Co., Ltd., trade name CE-2), oral administration of each sample 200 mg / kg body weight / day daily, and having all mice perform swimming exercise three times a week. It was bred for 4 weeks. In the 2nd week of breeding, attach a 2g weight to the tail of the mouse, let it swim in a water tank, and the time until it becomes impossible to continue the swimming exercise that causes the top of the mouse to sink under the water surface due to exhaustion (limit swimming time) ) Was measured. In addition, after the end of breeding, the blood of the mouse was collected, and the NO in the plasma obtained by centrifugation was measured using NO2 / NO3 Assay Kit-C II (Colorimetric) -Griess Reagent Kit- (manufactured by Dojin Chemical Laboratory). bottom. The blood NO concentration was expressed as an average value ± standard deviation as a relative value when the value of the control group was 100 (Table 4).
この結果を表４に示す。同表のデータから、本発明に係るマヌカの葉由来抽出物は血中のＮＯ濃度を顕著に増加させること及び限界遊泳時間も著しく延長することを確認した。 The results are shown in Table 4. From the data in the table, it was confirmed that the manuka leaf-derived extract according to the present invention significantly increases the NO concentration in blood and also significantly prolongs the limit swimming time.
試験例５：ヒトにおける抗疲労試験
試験に参加することに同意が得られた、日常的に運動を行う健常男性２０名（２１歳〜３０歳、平均年齢：２４．８歳）を、１群１０名で２群に分け、それぞれの群にプラセボ（マルトデキストリン）又は試料Ｍ−１を２００ｍｇ充填したゼラチンカプセルを１日１カプセル摂取してもらい、これを４週間続けた。被験者は、普段の生活通りに運動も継続的に実施し、疲労の評価として、Ｖｉｓｕａｌ Ａｎａｌｏｇ Ｓｃａｌｅ（ＶＡＳ）アンケート（「抗疲労臨床評価ガイドライン」、日本疲労学会、２０１１年）を実施した。データは、平均値±標準偏差で表わした（表５）。Test Example 5: Anti-fatigue test in humans One group of 20 healthy men (21 to 30 years old, average age: 24.8 years old) who consented to participate in the test and who exercise on a daily basis. Ten people were divided into two groups, and each group was asked to take one capsule daily of gelatin capsules filled with 200 mg of placebo (maltodextrin) or sample M-1, and this was continued for 4 weeks. The subjects continued to exercise as usual, and conducted a Visual Analog Scale (VAS) questionnaire ("Anti-fatigue clinical evaluation guideline", Japan Fatigue Society, 2011) as an evaluation of fatigue. The data are expressed as mean ± standard deviation (Table 5).
この結果を表５に示す。ＶＡＳ値は数値が低いほど疲労感が軽減されたことを示している。表５のデータから、本発明に係るマヌカの葉由来抽出物は、疲労感を低減させることが明らかとなった。 The results are shown in Table 5. The VAS value indicates that the lower the value, the less the feeling of fatigue. From the data in Table 5, it was clarified that the manuka leaf-derived extract according to the present invention reduces the feeling of fatigue.
試作例１
本発明のＮＯ産生促進剤としての試料Ｍ−１〜３のいずれか１種をカプセル充填機に供して、常法により１粒あたり内容量が２００ｍｇのゼラチン被覆ハードカプセル製剤を試作した。これらのカプセル製剤は経口摂取が可能な栄養補助食品、医薬品等として使用することができる。Prototype example 1
Any one of Samples M-1 to 3 as the NO production promoter of the present invention was subjected to a capsule filling machine, and a gelatin-coated hard capsule preparation having a content of 200 mg per capsule was prototyped by a conventional method. These capsule preparations can be used as dietary supplements, pharmaceuticals, etc. that can be taken orally.
試作例２
本発明のＮＯ産生促進剤として試料Ｍ−１〜３のいずれか１種：１５０部（質量基準。以下同様）、ミツロウ：４０部及び月見草油（英国エファモール社製）：８０部を約５０℃に加熱混合して均質にした後、カプセル充填機に供して、常法により１粒あたり内容量が２００ｍｇのゼラチン被覆ソフトカプセル製剤を試作した。これらのカプセル製剤は経口摂取可能な栄養補助食品として使用することができる。Prototype example 2
As the NO production promoter of the present invention, any one of Samples M-1 to 3: 150 parts (mass basis; the same applies hereinafter), evening primrose: 40 parts and evening primrose oil (manufactured by Efamol, UK): 80 parts at about 50 ° C. After heating and mixing to homogenize the mixture, the product was subjected to a capsule filling machine to prepare a gelatin-coated soft capsule preparation having a content of 200 mg per capsule by a conventional method. These capsule preparations can be used as dietary supplements that can be taken orally.
試作例３
本発明のＮＯ産生促進剤として試料Ｍ−１〜３のいずれか１種：３０部、緑茶抽出物（ビーエイチエヌ（株）製）：０．５部、コーンスターチ（日本コーンスターチ（株）製）：１０５部、リン酸三カルシウム（米山化学工業（株）製）：５０部及びリボフラビン（ＤＳＭニュートリション・ジャパン（株）製）：７部を混合機に仕込み、１０分間攪拌混合した。この混合物を直打式打錠機に供して直径７ｍｍ、高さ４ｍｍ、質量１５０ｍｇ／個の素錠を作成し、ついでコーティング機でシェラック被膜を形成させて錠剤形状の食品を試作した。Prototype example 3
As the NO production promoter of the present invention, any one of Samples M-1 to 3: 30 parts, green tea extract (manufactured by BHN Co., Ltd.): 0.5 parts, cornstarch (manufactured by Japan Corn Starch Co., Ltd.): 105 Parts, tricalcium phosphate (manufactured by Yoneyama Chemical Industry Co., Ltd.): 50 parts and riboflavin (manufactured by DSM Nutrition Japan Co., Ltd.): 7 parts were charged into a mixer and stirred and mixed for 10 minutes. This mixture was applied to a direct-type tableting machine to prepare uncoated tablets having a diameter of 7 mm, a height of 4 mm, and a mass of 150 mg / piece, and then a shellac coating was formed by a coating machine to make a prototype tablet-shaped food.
試作例４
市販の栄養ドリンク１００ｍＬに本発明のＮＯ産生促進剤として試料Ｍ−１〜３のいずれか１種：２００ｍｇ加えて十分に混合し飲料を試作した。これは冷蔵庫で１年間保存しても外観及び風味に異状及び違和感は認められなかった。尚、本品は、血管内皮細胞でのＮＯ産生促進、持久力の向上、疲労防止のために使用することができる。Prototype example 4
A beverage was prepared by adding 200 mg of any one of Samples M-1 to 3 as the NO production promoter of the present invention to 100 mL of a commercially available nutritional drink and mixing them sufficiently. No abnormality or discomfort was observed in the appearance and flavor even after storage in the refrigerator for 1 year. This product can be used to promote NO production in vascular endothelial cells, improve endurance, and prevent fatigue.
試作例５
即席麺の製造工程において、公知の原料に本発明のＮＯ産生促進剤として試料Ｍ−１〜３のいずれか１種を３００ｍｇ加えて即席麺を試作した。これは常温で６ヵ月間保存しても外観及び風味に異状及び違和感は認められなかった。尚、本品は、血管内皮細胞でのＮＯ産生促進、持久力の向上、疲労防止のために使用することができる。Prototype example 5
In the process of producing instant noodles, 300 mg of any one of Samples M-1 to 3 as a NO production promoter of the present invention was added to a known raw material to make an instant noodle as a trial product. No abnormality or discomfort was observed in the appearance and flavor even after storage at room temperature for 6 months. This product can be used to promote NO production in vascular endothelial cells, improve endurance, and prevent fatigue.
本発明の、フトモモ科ギョリュウバイ属に属するマヌカの葉の抽出物を有効成分として含有してなるＮＯ産生促進剤は、これを経口摂取することにより血管内皮細胞でのＮＯ産生を促進する作用を有するため、ＮＯ産生の促進及び／又は血管内皮細胞でのＮＯ産生の低下に起因する症状を改善するための飲食品、医薬品、医薬部外品、飼料等に有効利用することができる。 The NO production-promoting agent of the present invention containing an extract of Manuka leaves belonging to the genus Manuka of the Myrtaceae family as an active ingredient has an action of promoting NO production in vascular endothelial cells by ingesting it orally. Therefore, it can be effectively used for foods and drinks, pharmaceuticals, non-pharmaceutical products, feeds, etc. for promoting NO production and / or improving symptoms caused by decreased NO production in vascular endothelial cells.
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