JP2016044169A - Improver of vascular endothelial function - Google Patents
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Abstract
Description
本発明は複数種のスパイスを有効成分として含有する血管内皮機能の改善剤に関する。 The present invention relates to an agent for improving vascular endothelial function, comprising a plurality of spices as active ingredients.
血管内皮細胞は、一酸化窒素(Nitric Oxide,NO)、内皮由来過分極因子(endothelial derived hyperporlaring factor,EDHF)、プロスタグランジンI2といった種々の血管作動性物質を放出することで血管平滑筋緊張を調整するほか、細胞接着や血小板の粘着凝集を抑制するなど血管保護に関わる様々な機能を有する(非特許文献1)。これらの血管保護に関わる血管内皮機能の異常は、高血圧症、高脂血症、糖尿病といった生活習慣病、喫煙、閉経などで認められ、動脈硬化病変の端緒であると考えられている。 Vascular endothelial cells, nitric oxide (Nitric Oxide, NO), endothelium-derived hyperpolarizing factor (endothelial derived hyperporlaring factor, EDHF) , vascular smooth muscle tone by releasing various vasoactive substances such prostaglandin I 2 In addition to adjusting the above, it has various functions related to blood vessel protection such as suppressing cell adhesion and adhesion aggregation of platelets (Non-patent Document 1). These abnormalities of vascular endothelial function related to vascular protection are observed in lifestyle-related diseases such as hypertension, hyperlipidemia and diabetes, smoking, menopause, etc., and are considered to be the beginning of arteriosclerotic lesions.
非侵襲かつ反復可能な血管内皮機能測定方法として、FMD(Flow−Mediated Dilation)の測定が臨床的に頻繁に用いられている(非特許文献2)。 As a non-invasive and repeatable vascular endothelial function measuring method, FMD (Flow-Mediated Dilation) measurement is frequently used clinically (Non-patent Document 2).
FMD値は、食後の一時的な血糖上昇(糖負荷)によって低下することが知られている(非特許文献3、4、5)。これは、一般的に、血糖上昇による酸化ストレスの増加や炎症反応により血管内皮機能が低下することが原因であると考えられている。近年、食後高血糖が心血管イベントのリスクとなることが疫学研究において示されている(非特許文献6)。食後高血糖条件における血管内皮機能の改善は、動脈硬化病変等の予防に繋がることから、糖尿病や肥満傾向にない健常人においても求められている。
It is known that the FMD value decreases due to a temporary increase in blood sugar (sugar load) after a meal (
これまでに、糖尿病モデル動物において、クルクミンの継続投与により血管内皮機能の低下を改善できることが確認されている(非特許文献7)。また、ヒトにおいて、タマネギエキスの継続投与により、食後の血管内皮機能の低下を改善できることが確認されている(特許文献1)。しかしながら、これらの手法は、有効成分の継続的な投与下において、疾患又は摂取による血管内皮機能の「低下」を改善するのみであり、血管内皮機能のさらなる増進をもたらすことは示されていない。 So far, it has been confirmed that the decrease in vascular endothelial function can be improved by continuous administration of curcumin in diabetes model animals (Non-patent Document 7). In humans, it has been confirmed that continuous administration of onion extract can improve the decrease in post-meal vascular endothelial function (Patent Document 1). However, these approaches only improve “reduction” of vascular endothelial function due to disease or ingestion under continuous administration of the active ingredient and have not been shown to result in further enhancement of vascular endothelial function.
本発明は、継続的な投与をしなくても、かつ血管内皮機能の「低下」を抑制するだけでなく、血管内皮機能のさらなる増進をもたらすことを可能とする、血管内皮機能の改善剤を提供することを目的とする。 The present invention relates to an agent for improving vascular endothelial function, which can cause further enhancement of vascular endothelial function as well as suppressing “decrease” of vascular endothelial function without continuous administration. The purpose is to provide.
本発明者らは、上記課題を解決するために鋭意検討を重ねた結果、複数種のスパイスを含む組成物の単回投与により、血管内皮機能の改善及びさらなる増進をもたらすことを見出し、本発明を完成するに至った。 As a result of intensive studies to solve the above problems, the present inventors have found that a single administration of a composition containing a plurality of types of spices leads to improvement and further enhancement of vascular endothelial function. It came to complete.
すなわち、本発明は以下の発明を包含する。
[1] クローブ、コリアンダー、クミン、ニンニク、ショウガ、タマネギ、トウガラシ及びウコンを有効成分として含有する、血管内皮機能改善剤。
[2] 単回投与により、血管内皮機能の改善をもたらす、[1]の血管内皮機能改善剤。
[3] 食後における血管内皮機能の改善のための、[1]又は[2]の血管内皮機能改善剤。
That is, the present invention includes the following inventions.
[1] A vascular endothelial function improving agent comprising clove, coriander, cumin, garlic, ginger, onion, chili pepper and turmeric as active ingredients.
[2] The vascular endothelial function improving agent according to [1], wherein the vascular endothelial function is improved by a single administration.
[3] The vascular endothelial function improving agent according to [1] or [2] for improving vascular endothelial function after a meal.
本発明によれば、継続的な投与をしなくても、かつ血管内皮機能の「低下」を抑制するだけでなく、血管内皮機能のさらなる増進をもたらすことを可能とする、血管内皮機能の改善剤を提供することができる。 According to the present invention, it is possible to improve vascular endothelial function without allowing continuous administration and not only suppressing “decrease” of vascular endothelial function but also causing further enhancement of vascular endothelial function. An agent can be provided.
<有効成分>
本発明の血管内皮機能改善剤は、クローブ、コリアンダー、クミン、ニンニク、ショウガ、タマネギ、トウガラシ及びウコンを有効成分として含有する。なお、本明細書において、クローブは学名Syzygium aromaticumとする植物を指す。本発明に用いられるクローブの品種は限定されない。本発明においてクローブは、スパイスや漢方薬として一般的に用いられている開花前の花蕾部を少なくとも含んでいればよい。
<Active ingredient>
The vascular endothelial function improving agent of the present invention contains clove, coriander, cumin, garlic, ginger, onion, pepper and turmeric as active ingredients. In the present specification, clove refers to a plant having the scientific name Syzygium aromaticum. The variety of cloves used in the present invention is not limited. In the present invention, the clove only needs to contain at least the flower part before flowering that is generally used as a spice or a traditional Chinese medicine.
コリアンダーは学名Coriandrum sativumとする植物を指す。本発明に用いられるコリアンダーの品種は限定されない。本発明においてコリアンダーは、スパイスや漢方薬として一般的に用いられている果実部を少なくとも含んでいればよい。 Coriander refers to a plant with the scientific name Coriandrum sativum. The variety of coriander used in the present invention is not limited. In the present invention, coriander only needs to contain at least a fruit part generally used as a spice or herbal medicine.
クミンは学名Cuminum cyminumとする植物を指す。本発明に用いられるクミンの品種は限定されない。本発明においてクミンは、スパイスや漢方薬として一般的に用いられている種子部を少なくとも含んでいればよい。 Cumin refers to a plant with the scientific name Cuminum cyminum. The variety of cumin used in the present invention is not limited. In this invention, cumin should just contain the seed part generally used as a spice or a Chinese medicine.
トウガラシは学名Capsicum annuumに分類される植物を指す。本発明に用いられるトウガラシの品種は限定されない。本発明においてトウガラシは、スパイスや漢方薬として一般的に用いられている果実部を少なくとも含んでいればよい。 Pepper refers to plants classified under the scientific name Capsicum annuum. The kind of pepper used in the present invention is not limited. In the present invention, the red pepper only needs to contain at least a fruit part generally used as a spice or a traditional Chinese medicine.
ウコンは学名Curcuma longaに分類される植物を指す。本発明に用いられるウコンの品種は限定されない。本発明においてウコンは、スパイスや漢方薬として一般的に用いられている根茎部を少なくとも含んでいればよい。 Turmeric refers to plants classified under the scientific name Curcuma longa. The varieties of turmeric used in the present invention are not limited. In the present invention, the turmeric only needs to contain at least a rhizome part generally used as a spice or a traditional Chinese medicine.
クローブ、コリアンダー、クミン、トウガラシ及びウコンはそれぞれ、スパイスや漢方薬として一般的に用いられている形態、例えば、乾燥物及び/又は破砕物等の形態のものを利用することができる。「乾燥物」は、風乾、加熱乾燥、凍結乾燥、減圧乾燥等の通常の乾燥手段を用いて得ることができる。「破砕物」は、ミキサー、コミトロール、ミクロマイスター等を用いて粉砕することにより調製することができる。 Clove, coriander, cumin, red pepper and turmeric can each be used in the form commonly used as spices and herbal medicines, for example, dried and / or crushed. The “dried product” can be obtained by using ordinary drying means such as air drying, heat drying, freeze drying, and reduced pressure drying. The “crushed material” can be prepared by pulverization using a mixer, a comitrol, a micromeister, or the like.
ニンニクは学名Allium sativumに分類される植物を指す。本発明に用いられるニンニクの品種は限定されない。本発明においてニンニクは、スパイスや漢方薬として一般的に用いられている球の部分(鱗茎部)を少なくとも含んでいればよい。 Garlic refers to plants classified under the scientific name Allium sativum. The garlic variety used in the present invention is not limited. In this invention, the garlic should just contain the part (bulb part) of the bulb | ball generally used as a spice or a Chinese medicine.
ショウガは学名Zingiber officinaleに分類される植物を指す。本発明に用いられるショウガの品種は限定されない。本発明においてショウガは、スパイスや漢方薬として一般的に用いられている地下茎部を少なくとも含んでいればよい。 Ginger refers to plants classified under the scientific name Zingiber officinale. The variety of ginger used in the present invention is not limited. In the present invention, ginger only needs to contain at least a rhizome part generally used as a spice or a traditional Chinese medicine.
タマネギは学名Allium cepaに分類される植物を指す。本発明に用いられるタマネギの品種は限定されない。本発明に用いられるタマネギは、通常食用される球の部分(鱗茎部)を少なくとも含んでいればよい。鱗茎部の外皮、タマネギの他の部位(葉、根)を含んでいるか否かは問わない。本発明に用いられるタマネギは、典型的には、外皮を有するタマネギ鱗茎部、又は外皮が除去されたタマネギ鱗茎部である。 Onion refers to plants classified under the scientific name Allium cepa. The variety of onion used in the present invention is not limited. The onion used for this invention should just contain the part (bulb part) of the bulb | ball normally eaten. It does not matter whether the outer skin of the bulb portion or other parts (leaves, roots) of the onion are included. The onion used in the present invention is typically an onion bulb portion having an outer skin or an onion bulb portion from which the outer skin has been removed.
ニンニク、ショウガ及びタマネギは、上記乾燥物及び/又は破砕物の形態、或いは電子レンジ加熱、ボイリング、蒸気加熱、焼く、炒める等により加熱処理された形態のものを利用することができる。加熱処理されたものは適当な寸法及び形状にカットされた状態のものを用いることができる。 Garlic, ginger and onion can be used in the form of the dried product and / or crushed product, or in the form of heat treatment by microwave heating, boiling, steam heating, baking, frying, and the like. What was heat-processed can use the thing cut in the suitable dimension and shape.
上記の各有効成分は、搾汁、抽出液、あるいは前記搾汁若しくは抽出液又はそれら混合物を濃縮又は乾燥した濃縮物又は乾燥物の形態であってもよい。「搾汁」は、各有効成分を破砕・圧搾して、液体画分と細胞壁等の固体画分とを分離し、液体画分を取得することにより調製することができる。液体画分と固体画分との分離は遠心分離、ろ過(例えば珪藻土ろ過)等の通常の固液分離手段により行うことができる。「抽出液」は、各有効成分を抽出媒体により抽出することにより調製することができる。抽出媒体としては有機溶媒、水等の溶媒、超臨界二酸化炭素等の超臨界流体が挙げられ、溶媒が特に好ましい。溶媒としては水や、エタノール等のアルコール、アセトン等の親水性有機溶媒、ヘキサン、あるいはそれらの混合溶媒を用いることができる。溶媒抽出により抽出液を製造する場合には、各有効成分を適量の溶媒(例えば各有効成分に対して重量基準で0.5〜20倍量)中に浸漬し、適宜撹拌又は静置して溶媒中に溶媒可溶性成分を溶出させる。抽出時間は特に限定されないが、5分間〜120分間、例えば、15分間〜30分間とすることができる。抽出温度は特に限定されないが、0℃〜125℃、例えば60℃〜125℃とすることができる。抽出後、溶媒可溶性成分を含む溶媒画分と細胞壁等の固体画分とを上述の固液分離手段により分離し、溶媒画分を抽出液として取得する。抽出に用いる各有効成分の形状は、原型のまま、或いは適当な寸法又は形状にカットした状態、或いは上記の乾燥物、破砕物、又は搾汁の形状であることができる。前記「濃縮物又は乾燥物」は、前記搾汁又は抽出液あるいはそれら混合物を濃縮又は乾燥することにより製造することができる。ここで濃縮とは搾汁又は抽出液あるいはこれらの混合物中の液体(水及び/又は抽出溶媒)を減少させて最終糖濃度を50%以上とすることを指す。糖濃度は市販の糖度計で測定することができる。濃縮の方法としては、例えば真空蒸発濃縮、膜濃縮が採用できる。真空蒸発濃縮は一般的に減圧濃縮と呼ばれる。濃縮時の真空度は最終品を糖度50%と以上とすることができる範囲で選択でき、特に限定されない。膜濃縮は、例えば逆浸透膜(RO)、限外ろ過膜(UF)等の膜を使用して行うことができる。使用する膜の種類は糖度50%以上とすることができる範囲で選択でき、特に限定されない。乾燥は前記搾汁又は抽出液あるいはそれら混合物を前記通常の乾燥手段を用いて乾燥することにより実施することができる。濃縮又は乾燥に際して、前記搾汁、前記抽出液、又は前記濃縮物と賦形剤等の他の成分とを組み合わせて濃縮又は乾燥を行ってもよい。 Each active ingredient described above may be in the form of a juice or extract, or a concentrate or dried product obtained by concentrating or drying the juice or extract or a mixture thereof. The “squeezed juice” can be prepared by crushing / squeezing each active ingredient, separating the liquid fraction and the solid fraction such as the cell wall, and obtaining the liquid fraction. Separation of the liquid fraction and the solid fraction can be performed by ordinary solid-liquid separation means such as centrifugation and filtration (for example, diatomaceous earth filtration). The “extract” can be prepared by extracting each active ingredient with an extraction medium. Examples of the extraction medium include organic solvents, solvents such as water, and supercritical fluids such as supercritical carbon dioxide, and solvents are particularly preferable. As the solvent, water, alcohol such as ethanol, hydrophilic organic solvent such as acetone, hexane, or a mixed solvent thereof can be used. When producing an extract by solvent extraction, each active ingredient is immersed in an appropriate amount of solvent (for example, 0.5 to 20 times the weight of each active ingredient), and stirred or allowed to stand as appropriate. The solvent soluble component is eluted in the solvent. The extraction time is not particularly limited, but can be 5 minutes to 120 minutes, for example, 15 minutes to 30 minutes. Although extraction temperature is not specifically limited, It can be set as 0 to 125 degreeC, for example, 60 to 125 degreeC. After extraction, a solvent fraction containing a solvent-soluble component and a solid fraction such as a cell wall are separated by the above-mentioned solid-liquid separation means, and the solvent fraction is obtained as an extract. The shape of each active ingredient used for extraction can be the original shape, a state cut into an appropriate size or shape, or the shape of the dried product, crushed product, or juice. The “concentrate or dried product” can be produced by concentrating or drying the juice or extract or a mixture thereof. Here, the concentration refers to reducing the liquid (water and / or extraction solvent) in the squeezed or extracted liquid or a mixture thereof to make the final sugar concentration 50% or more. The sugar concentration can be measured with a commercially available saccharimeter. As a concentration method, for example, vacuum evaporation concentration or membrane concentration can be employed. Vacuum evaporation concentration is generally called vacuum concentration. The degree of vacuum at the time of concentration can be selected as long as the final product can have a sugar content of 50% or more, and is not particularly limited. Membrane concentration can be performed using a membrane such as a reverse osmosis membrane (RO) or an ultrafiltration membrane (UF). The type of membrane to be used can be selected within a range where the sugar content can be 50% or more, and is not particularly limited. Drying can be carried out by drying the juice or extract or a mixture thereof using the usual drying means. At the time of concentration or drying, concentration or drying may be performed by combining the juice, the extract, or the concentrate with other components such as excipients.
本発明の血管内皮機能改善剤に含まれる各有効成分の含有量は特に限定されないが、単回投与による投与量にして、例えば以下の範囲よりそれぞれ選択される量(乾燥重量に基づく)を含めることができる。
クローブ:0.01〜3g、好ましくは0.5〜2g。
コリアンダー:0.01〜20g、好ましくは1〜5g。
クミン:0.01〜20g、好ましくは0.5〜5g。
ニンニク:0.01〜20g、好ましくは1〜5g。
ショウガ:0.01〜20g、好ましくは1〜5g。
トウガラシ:0.001〜2g、好ましくは0.05〜0.5g。
ウコン:0.01〜20g、好ましくは1〜10g。
タマネギ:0.01〜20g、好ましくは1〜10g。
The content of each active ingredient contained in the vascular endothelial function improving agent of the present invention is not particularly limited, but includes, for example, an amount selected from the following ranges (based on dry weight) as a single dose be able to.
Cloves: 0.01 to 3 g, preferably 0.5 to 2 g.
Coriander: 0.01 to 20 g, preferably 1 to 5 g.
Cumin: 0.01-20 g, preferably 0.5-5 g.
Garlic: 0.01-20 g, preferably 1-5 g.
Ginger: 0.01-20 g, preferably 1-5 g.
Pepper: 0.001-2 g, preferably 0.05-0.5 g.
Turmeric: 0.01 to 20 g, preferably 1 to 10 g.
Onion: 0.01-20 g, preferably 1-10 g.
一実施形態において、本発明の血管内皮機能改善剤は、クローブ:0.5〜1g、コリアンダー:1〜2g、クミン:0.5〜1g、ニンニク:2〜5g、ショウガ:2〜5g、トウガラシ:0.05〜0.2g、ウコン:2〜5gを含み、タマネギを:5〜15g含む(ここで、クローブ、コリアンダー、クミン、ニンニク、ショウガ、トウガラシ、及びウコンは乾燥粉末の形態にて、タマネギは加熱処理された形態にて含む)。 In one embodiment, the vascular endothelial function-improving agent of the present invention contains clove: 0.5-1 g, coriander: 1-2 g, cumin: 0.5-1 g, garlic: 2-5 g, ginger: 2-5 g, pepper : 0.05-0.2 g, Turmeric: 2-5 g, Onion: 5-15 g (where clove, coriander, cumin, garlic, ginger, pepper, and turmeric are in the form of dry powder, Onion is included in the form of heat-treated).
<血管内皮機能改善剤>
本発明の血管内皮機能改善剤は、血管内皮機能を改善する能力を有する。血管内皮機能とは、上記したとおり、一酸化窒素(NO)、内皮由来過分極因子(EDHF)、プロスタグランジンI2といった種々の血管作動性物質を放出することで血管平滑筋緊張を調整するほか、細胞接着や血小板の粘着凝集を抑制するなど血管保護に関わる様々な機能を意味する。血管内皮機能は、手又は足の駆血後の血流依存性血管拡張反応(FMD(Flow−Mediated Dilation))による血管径の増大率(FMD値(%))に基づき評価することができる。FMD値の値が大きいほど血管内皮機能が高いことを示す。FMD値の測定は通常のFMD検査装置により行うことができる。
<Vascular endothelial function improver>
The vascular endothelial function improving agent of the present invention has an ability to improve vascular endothelial function. Vascular endothelial function, as described above, nitric oxide (NO), adjusts the vascular smooth muscle tone by releasing various vasoactive substances such endothelium-derived hyperpolarizing factor (EDHF), prostaglandin I 2 In addition, it means various functions related to blood vessel protection, such as suppressing cell adhesion and adhesion aggregation of platelets. The vascular endothelial function can be evaluated based on the rate of increase in blood vessel diameter (FMD value (%)) by blood flow-dependent vasodilation (FMD (Flow-Mediated Dilation)) after hand or foot blood transfusion. A larger FMD value indicates a higher vascular endothelial function. The FMD value can be measured with a normal FMD inspection apparatus.
ヒトでの血管内皮機能の測定方法としてはFMDが一般的であるが、他にストレインゲージ・プレチスモグラフィを用いる方法、指尖容積脈波を用いる方法(Endo−PAT)等のFMD以外の方法を用いても構わない。また、血管内皮機能はヒトで測定することが好ましいが、in vivoまたはex vivo動物試験や内皮細胞を用いたNO産生能等のin vitroの指標で確認しても構わない。 FMD is generally used as a method for measuring vascular endothelial function in humans, but other methods than FMD such as a method using strain gauge plethysmography, a method using fingertip volume pulse wave (Endo-PAT), etc. You may use. Vascular endothelial function is preferably measured in humans, but it may be confirmed by in vitro or ex vivo animal tests or in vitro indicators such as NO production ability using endothelial cells.
本発明の血管内皮機能改善剤は、動脈硬化症、慢性腎臓病(CKD)、高血圧、脂質代謝異常症、糖尿病、肥満・メタボリック症候群、冠動脈疾患、脳血管疾患、播種性血管内凝固症候群(DIC)、膠原病等の疾患の予防又は治療のために用いることができる。本発明の血管内皮機能改善剤は、糖尿病患者や、肥満傾向にある対象者だけでなく、健常な対象者に対しても有効である。 The vascular endothelial function improving agent of the present invention includes arteriosclerosis, chronic kidney disease (CKD), hypertension, dyslipidemia, diabetes, obesity / metabolic syndrome, coronary artery disease, cerebrovascular disease, disseminated intravascular coagulation syndrome (DIC). ), Can be used for the prevention or treatment of diseases such as collagen disease. The vascular endothelial function improving agent of the present invention is effective not only for diabetic patients and subjects who are obese, but also for healthy subjects.
本発明の血管内皮機能改善剤は、食後の血糖上昇による血管内皮機能の低下を抑制することが可能である。さらに、本発明の血管内皮機能改善剤は、血管内皮機能を増進することができる。「血管内皮機能を増進する」とは、食後の血糖上昇による血管内皮機能の低下を抑制する以上の効果を意味し、血管内皮機能を低下する以前の水準を上回る水準にまで向上させることを意味する。 The vascular endothelial function improving agent of the present invention can suppress a decrease in vascular endothelial function due to an increase in blood glucose after a meal. Furthermore, the vascular endothelial function improving agent of the present invention can enhance vascular endothelial function. “Promoting vascular endothelial function” means more than suppressing the decrease in vascular endothelial function due to postprandial blood glucose increase, and means improving to a level higher than the level before vascular endothelial function was decreased. To do.
本発明の血管内皮機能改善剤の対象は典型的にはヒトであるが、ヒトには限定されず他の非ヒト動物、例えばヒト以外の哺乳類であってもよい。 The subject of the vascular endothelial function improving agent of the present invention is typically a human, but is not limited to a human and may be other non-human animals, for example, mammals other than humans.
本発明の血管内皮機能改善剤は医薬品(医薬部外品に分類されるものも含む。以下同じ)の形態で用いることができる。 The vascular endothelial function improving agent of the present invention can be used in the form of pharmaceuticals (including those classified as quasi-drugs; the same applies hereinafter).
本発明の血管内皮機能改善剤は、上記の所定の量にて上記各有効成分を含み、全体が上記有効成分のみからなるものであってもよいし、上記有効成分と他の成分とを含むものであってもよい。「他の成分」は、医薬品において許容される成分である限り特に限定されず、例えば、賦形剤、崩壊剤、滑沢剤、結合剤、酸化防止剤、着色剤、凝集防止剤、吸収促進剤、溶解補助剤、安定化剤などの製剤素材を挙げることができ、本発明の血管内皮機能改善剤の剤形に応じて、適当なものを選択し、適宜組み合わせて用いることができる。 The vascular endothelial function improving agent of the present invention contains each of the above-mentioned active ingredients in the above-mentioned predetermined amount, and may consist entirely of the above-mentioned active ingredients, or may contain the above-mentioned active ingredients and other ingredients. It may be a thing. “Other components” are not particularly limited as long as they are components acceptable in pharmaceuticals. For example, excipients, disintegrants, lubricants, binders, antioxidants, colorants, anti-aggregation agents, absorption enhancers Preparation materials such as agents, solubilizers, stabilizers, and the like. Appropriate ones can be selected according to the dosage form of the vascular endothelial function improving agent of the present invention, and can be used in appropriate combination.
本発明の血管内皮機能改善剤の剤形は、特に限定されず、例えば、カプセル剤、錠剤、顆粒剤、細粒剤、カプレット、散剤、液剤、トローチなどの剤形が挙げられる。経口投与可能な形態であることが好ましいが、これには限定されず、他の経路、例えば舌下投与、吸入等の経路で投与される形態であってもよい。 The dosage form of the vascular endothelial function improving agent of the present invention is not particularly limited, and examples thereof include capsules, tablets, granules, fine granules, caplets, powders, liquids, troches and the like. It is preferably in a form that can be administered orally, but is not limited thereto, and may be a form that is administered by other routes such as sublingual administration or inhalation.
本発明の血管内皮機能改善剤は、単回投与により、血管内皮機能の低下の抑制効果、及び/又は、血管内皮機能の増進の効果を得ることができる。より詳細には、単回投与後、4時間以内、3時間以内、2時間以内、1時間以内、又は30分間以内には上記効果を得ることができる。「単回投与」とは、一度に投与されること、あるいは短い時間(例えば2時間以下、1時間以下、30分間以下、20分間以下、10分間以下、又は5分間以下)の間に連続的に複数回で投与されることを意味する。なお、本発明の血管内皮機能改善剤は天然由来の成分を有効成分とし、継続的な投与を可能とするものであり、用法を単回投与に限定するものではない。本発明の血管内皮機能改善剤は、特に限定されないが、食事の前後2時間以内、1時間以内、又は30分間以内、あるいは食事と同時に投与されることが好ましい。これにより、食後の血糖上昇による血管内皮機能の低下を抑制すると共に、血管内皮機能を増進することができる。また、本発明の血管内皮機能改善剤は、飲食品に含めて提供・摂取されてもよい。 The agent for improving vascular endothelial function of the present invention can obtain the effect of suppressing the decrease in vascular endothelial function and / or the effect of promoting vascular endothelial function by single administration. More specifically, the above effect can be obtained within 4 hours, within 3 hours, within 2 hours, within 1 hour, or within 30 minutes after a single administration. “Single dose” refers to administration at a time or continuous for a short period of time (eg, 2 hours or less, 1 hour or less, 30 minutes or less, 20 minutes or less, 10 minutes or less, or 5 minutes or less). Means to be administered multiple times. In addition, the vascular endothelial function improving agent of the present invention uses a naturally-derived component as an active ingredient and enables continuous administration, and the usage is not limited to single administration. Although the vascular endothelial function improving agent of the present invention is not particularly limited, it is preferably administered within 2 hours, within 1 hour, or within 30 minutes, or simultaneously with a meal. Thereby, while suppressing the fall of the vascular endothelial function by the blood glucose rise after a meal, a vascular endothelial function can be promoted. Moreover, the vascular endothelial function improving agent of this invention may be provided and ingested by including in food-drinks.
材料と方法
被験者と試験デザイン
14名の健常男性(45±9歳、BMI23.7±2.7kg/m2)を被験者とし、第1群(7名)及び第2群(7名)に無作為に振り分け、クロスオーバー試験を行った。なお、被験者は試験開始のおよそ12時間前から飲食が禁じられ(水のみ摂取可)、空腹状態にて試験に参加した。
Materials and methods
Subjects and study design 14 healthy men (45 ± 9 years old, BMI 23.7 ± 2.7 kg / m 2 ) as subjects, randomly assigned to group 1 (7) and group 2 (7) A crossover test was conducted. The subjects were prohibited from eating or drinking from about 12 hours before the start of the test (only water could be taken), and participated in the test on an empty stomach.
クロスオーバー試験の概要を図1に示す。すなわち、第1群はまず、コントロール食を摂取する第1回試験を行い、コントロール食摂取前の空腹時におけるFMD値及びコントロール食摂取から1時間後のFMD値を測定した。次いで、第1回試験から1週間後に、試験食を摂取する第2回試験を行い、試験食摂取前の空腹時におけるFMD値及び試験食摂取から1時間後のFMD値を測定した。一方、第2群はまず、試験食を摂取する第1回試験を行い、試験食摂取前の空腹時におけるFMD値及び試験食摂取から1時間後のFMD値を測定した。次いで、第1回試験から1週間後に、コントロール食を摂取する第2回試験を行い、コントロール食摂取前の空腹時におけるFMD値及びコントロール食摂取から1時間後のFMD値を測定した。 An outline of the crossover test is shown in FIG. That is, the first group first performed a first test for ingesting a control food, and measured the FMD value at the time of fasting before ingesting the control food and the FMD value 1 hour after the intake of the control food. Then, one week after the first test, a second test of ingesting the test meal was performed, and the FMD value in the fasting state before ingesting the test meal and the FMD value 1 hour after ingestion of the test meal were measured. On the other hand, the second group first conducted a first test for ingesting the test meal, and measured the FMD value on an empty stomach before ingestion of the test meal and the FMD value 1 hour after ingestion of the test meal. Then, one week after the first test, a second test of ingesting the control food was performed, and the FMD value in the fasting state before ingesting the control food and the FMD value 1 hour after ingesting the control food were measured.
試験食
クローブ0.9g、コリアンダー1.8g、クミン0.9g、ニンニク3.6g、ショウガ2.7g、タマネギ9g、トウガラシ0.09g、及びウコン4.5gを含むスパイスミックスをミートソース180g及び米飯200gと混合し、試験食を得た。クローブ、コリアンダー、クミン、ニンニク、ショウガ、トウガラシ、及びウコンは乾燥粉末の形態のものを用いた。タマネギは皮をむき、1/4カットしたものをソテーし、加熱処理したものを用いた。
Spice mix containing test food clove 0.9g, coriander 1.8g, cumin 0.9g, garlic 3.6g, ginger 2.7g, onion 9g, pepper 0.09g, turmeric 4.5g meat sauce 180g and cooked rice 200g To obtain a test meal. Clove, coriander, cumin, garlic, ginger, pepper, and turmeric were in the form of dry powder. The onion used was peeled, sauteed a quarter cut, and heat-treated.
コントロール食
コントロール食は、上記試験食よりスパイスミックスを除いたものを使用した。すなわち、ミートソース180g及び米飯200gとを混合し、コントロール食を得た。
As the control food, a food obtained by removing the spice mix from the test food was used. That is, 180 g of meat sauce and 200 g of cooked rice were mixed to obtain a control food.
FMD値の測定
FMD値の測定には(株)ユネクス社のFMD測定装置を用いた。測定方法は、既に報告されているFMD値測定のガイドラインに準じて行った(T Inoue, H et al Flow-mediated vasodilation as a diagnostic modality for vascular failure. Hypertens Res, 2008; 31(12): 2105-2113; 及び Mary C. et al Guidelines for the ultrasound assessment of endothelial-dependent flow - mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J. Am. Coll. Cardiol., 2002; 39(2): 257-265)。
Measurement of FMD Value An FMD measurement device manufactured by UNEX Corporation was used for measurement of the FMD value. Hypertens Res, 2008; 31 (12): 2105- The measurement method was performed according to the guideline of the FMD value measurement already reported (T Inoue, H et al Flow-mediated vasodilation as a diagnostic modality for vascular failure. 2113; and Mary C. et al Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J. Am. Coll. Cardiol., 2002; 39 ( 2): 257-265).
すなわち、ベッドに移動し、20分間の安静の後、定法にてFMD値を測定した。なお、試験食又はコントロール食の摂取前の測定時にサージカルテープにて測定位置をマークし、摂取後の測定時にも同じ位置で測定を行った。検査時には、肘からの測定位置までの距離を計測し、第2回試験時の測定においても、測定位置を揃えるようにした。 That is, after moving to a bed and resting for 20 minutes, the FMD value was measured by a conventional method. In addition, the measurement position was marked with the surgical tape at the time of measurement before ingestion of the test food or the control food, and the measurement was performed at the same position at the time of measurement after ingestion. At the time of the inspection, the distance from the elbow to the measurement position was measured, and the measurement position was aligned in the measurement at the second test.
結果
結果を図2に示す。各結果は、測定されたFMD値の平均値を示す。
The result is shown in FIG. Each result shows the average value of the measured FMD values.
コントロール食の摂取によりFMD値は5.8%から5.1%へと有意な低下が確認された。一方、試験食の摂取においては、FMD値は5.2%から6.6%へと有意な上昇が確認された。 It was confirmed that the FMD value significantly decreased from 5.8% to 5.1% by ingesting the control food. On the other hand, in the intake of the test meal, the FMD value was significantly increased from 5.2% to 6.6%.
これらの結果は、食後の血糖値の上昇により生じる酸化ストレスによって血管内皮機能が低下するのに対して、スパイスミックスを摂取した場合には、前記食後の血管内皮機能の低下を抑制するだけでなく、血管内皮機能のさらなる増進が確認された。また、その効果は、スパイスミックスの単回投与により、直ちに確認することができた。 These results show that vascular endothelial function is reduced by oxidative stress caused by an increase in blood glucose level after meals, whereas ingestion of spice mix not only suppresses the decrease in vascular endothelial function after meals. Further enhancement of vascular endothelial function was confirmed. The effect could be immediately confirmed by a single administration of the spice mix.
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