JP4993979B2 - Capillary circulatory improving agent containing Raffma extract component - Google Patents

Capillary circulatory improving agent containing Raffma extract component

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JP4993979B2
JP4993979B2 JP2006250107A JP2006250107A JP4993979B2 JP 4993979 B2 JP4993979 B2 JP 4993979B2 JP 2006250107 A JP2006250107 A JP 2006250107A JP 2006250107 A JP2006250107 A JP 2006250107A JP 4993979 B2 JP4993979 B2 JP 4993979B2
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昌夫 森
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株式会社和漢生薬研究所
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Description

本発明は、毛細血管の密度や血流速度を改善するラフマ抽出成分を含有する毛細血管循環改善剤の技術分野に属する。   The present invention belongs to the technical field of a capillary circulation improving agent containing a rough extract component that improves the density and blood flow velocity of capillaries.

従来、微小血管である指先の爪上皮の毛細血管の血流の動きを拡大して観測することによって、毛細血管の直径,血液速度,流量,血管密度などの連続的で動的な測定をすることができ、この毛細血管の状態を観測するために、本発明者らは、既に、特許3025671号(特許文献1)として提供しているものであるが、微小血管本数は多い方が血行が良という傾向が強く、血流速度も早い方が血流状態が良いことが知られている。
この毛細血管の密度や血流速度を改善するために、本発明者らは、特許3545290号(特許文献2)として、霊芝の炭化物を食品添加物や食品付加剤として用いることが有効であることを見出している。
ところで、従来、ラフマ(羅布麻)(学名:Apocynum venetum )は、中国に広く分布しているキョウチクトウ科の多年生宿草本(草本とは、俗に”草”と呼ばれているもの)植物であり、ラフマは繊維質に富んで麻のように用いられてきたことと、原産地が中国新疆地区の「ロプノール(羅布泊)」であることから『羅布麻』と命名されている。ラフマは植物であるため、産地の土壌、気候の変化、日射時間、降雨量などに影響されやすい、含有成分や有効成分の含量はかなり異なる。
中国では、古来より羅布麻の葉をお茶の葉の代わりとして利用しており、また、そのラフマ茶は、解熱などの民間薬としても利用されている。さらに、中国の複数の研究機関が民間薬として利用されているラフマ葉について医学的および薬学的に研究を重ねており、その結果、高血圧、心不全、気管支炎、水腫等に有効であることが報告されている。一方、日本においてもラフマ茶は、例えば、商品名:燕龍茶として市販されており、いろいろな作用を持つお茶として注目されている。
また、ラフマ葉を焙煎してコレステロール低下作用を高めたラフマ茶は特許第3517318号(特許文献3)に開示され、ラフマの抽出物を腸管出血大腸菌等の腸管感染症の予防・治療に用いることは特開平10-167978号公報(特許文献4)に開示され、フラボノイド化合物のイソクェルシトリンをラフマ葉から抽出して鬱病の抗鬱剤特開2002-201139号(特許文献5)として用いることが開示されている。
なお、ラフマ葉の効用について「生薬学」には、鎮静;頭痛、眩暈;高血圧;利尿;肝機能補助などが書かれているが、毛細血管循環の改善作用を有することは知られていない。
Conventionally, continuous and dynamic measurement of capillary diameter, blood velocity, flow rate, blood vessel density, etc. is performed by magnifying and observing the movement of capillary blood flow in the nail epithelium of the fingertip, which is a microvessel. In order to observe the state of the capillary, the present inventors have already provided as Patent No. 3025671 (Patent Document 1), and the blood circulation is increased when the number of microvessels is larger. It is known that the better the blood flow rate is, the better the blood flow rate is.
In order to improve the density and blood flow velocity of the capillaries, it is effective for the present inventors to use ganoderma carbide as a food additive or food additive as Patent No. 3545290 (Patent Document 2). I have found that.
By the way, traditionally, Rahuma (scientific name: Apocynum venetum) is a perennial herbaceous herbaceous plant that is widely distributed in China (herbaceous is what is commonly called "grass"). Rafuma is named “Rafu hemp” because it is rich in fiber and used like hemp and its origin is “Lopnor” in Xinjiang, China. Since Raffma is a plant, its contents and active ingredients are quite different, which is easily affected by soil, climate change, solar radiation time, rainfall, etc.
In China, Rafu hemp leaves have been used as a substitute for tea leaves since ancient times, and the rafuma tea has also been used as a folk medicine for antipyretic and so on. In addition, several Chinese research institutes are conducting medical and pharmaceutical research on Rahuma leaves, which are used as folk medicines, and as a result, they are reported to be effective for hypertension, heart failure, bronchitis, edema, etc. Has been. On the other hand, in Japan, Rama tea is marketed as, for example, trade name: Oolong tea, and is attracting attention as a tea having various effects.
Also, Raffa tea with roasted Raffa leaves to enhance cholesterol-lowering effect is disclosed in Japanese Patent No. 3517318 (Patent Document 3), and Raffa extract is used for the prevention and treatment of intestinal infections such as enterohemorrhagic Escherichia coli. This is disclosed in Japanese Patent Application Laid-Open No. 10-167978 (Patent Document 4), and isoflavcitrin, which is a flavonoid compound, is extracted from rafuma leaves and used as an antidepressant for depression, Japanese Patent Application Laid-Open No. 2002-201139 (Patent Document 5). Is disclosed.
Regarding the effect of Luffa leaves, “Biopharmaceutical” describes sedation; headache, dizziness; hypertension; diuresis; liver function assistance, etc., but it is not known to have an effect of improving capillary circulation.

特許3025671号公報Japanese Patent No. 3025671 特許3545290号公報Japanese Patent No. 3545290 特許第3517318号公報Japanese Patent No. 3517318 特開平10-167978号公報JP-A-10-167978 特開2002-201139号公報JP 2002-201139 A

本発明は、ラフマ葉の抽出成分を用いて、人体に安全であって、血圧や毛細血管の密度や血流速度等の血行を改善する毛細血管循環改善剤を提供することである。   An object of the present invention is to provide an agent for improving capillary circulation that is safe for the human body and improves blood circulation such as blood pressure, capillary density, blood flow velocity, and the like, using an extracted component of Rahma leaves.

上記の課題を解決するために、請求項1の発明は、イソクェルシトリンを6重量%以上、クェルセチンを0.3重量%以上の高含量を有するラフマ葉エキスを10〜25重量%と、イチョウの葉エキスが8〜12重量%と、甘草エキスが8〜12重量%とを混合したことを特徴とするラフマ抽出成分を含有する毛細血管循環改善剤である。
In order to solve the above-mentioned problems, the invention of claim 1 is characterized in that isoquercitrin is 6 wt% or more, quercetin is 0.3 wt% or more of Raffa leaf extract having a high content of 10 to 25 wt%, and leaf extract 8-12% ginkgo, a capillary circulation improving agent containing a Lafuma extracted components sweet grass extract which is characterized in that a mixture of a 8-12% by weight.

本発明によれば、ラフマ葉の抽出成分を用いているので人体に安全であり、高血圧患者に対して血圧を降下する作用効果があり、微小循環血管である毛細血管の密度を高め、毛細血管での血流速度を速め、血流量を増やし、毛細血管の血管口径を拡げる等の改善作用がある。
According to the present invention, because of the use of extracted components La fumarate leaves are safe to the human body, there are advantageous effects of lowering blood pressure with respect to hypertensive patients, increasing the density of the capillaries is microcirculatory blood vessels, capillary There are improving effects such as increasing the blood flow velocity in the blood vessel, increasing the blood flow volume, and expanding the blood vessel diameter of the capillary blood vessel.

本発明の特徴は、ラフマ葉の効用は、鎮静;頭痛、眩暈;高血圧;利尿;肝機能補助などが知られているが、イソクェルシトリンとクェルセチンの高含量を有するラフマ葉エキスを主剤とする本発明品について、動物実験と臨床実験を実施したところ、上述の効用は勿論であるが、新たな毛細血管循環の改善作用も見出したものである。
本発明は、前記イソクェルシトリンとクェルセチンの高含量を有するラフマ葉エキス、甘草エキス、イチョウ葉エキスの3成分を主剤とし、中でも前記ラフマ葉エキスを最重要成分としたもので、他の主成分の甘草エキスは動悸、ヒステリー、咽喉炎症、咳、中毒(食物、薬物)治療、腹痛、肝臓保護、副腎皮質機能低下、皮膚炎症、薬物の調和などに使われ、イチョウ葉エキスは、脳血管障害後遺症、痴呆補助治療、気管支炎、鎮静などに使われているが、本発明は、前記ラフマ葉エキス、イチョウの葉エキス、甘草エキスの三者の混合によって、いままで知見されていない毛細血管に対する効用があることに想到した。
以下に実施例を参照して本発明を説明するが、効果の確認のために、ラットによる動物実験と、高血圧患者を対象とした人の臨床実験を行った。
Feature of the present invention, the utility of Lafuma leaves, sedation; headache, dizziness; hypertension; diuretic; the like liver function aid is known, main ingredient Lafuma leaves equi scan with a high content of iso Beautique Le citrine and quercetin As a result of conducting animal experiments and clinical experiments on the product of the present invention, it has been found that, as well as the above-mentioned effects, a new effect of improving capillary circulation is also found.
The present invention Lafuma leaf extract with a high content of the iso Beautique Le citrine and quercetin, licorice extract, and a main agent of the three components of the Ginkgo biloba extract, in among them those the Lafuma leaves equi scan the most important components, other The main ingredient licorice extract is used for palpitations, hysteria, throat inflammation, cough, poisoning (food, drugs) treatment, abdominal pain, liver protection, adrenal cortex function decline, skin inflammation, drug harmony, etc. It is used for sequelae of vascular disorders, dementia assistive treatment, bronchitis, sedation, etc., but the present invention is a capillary that has not been discovered so far by mixing the above three of Luffa leaf extract, Ginkgo biloba extract, and licorice extract. I came up with the effect on blood vessels.
In the following, the present invention will be described with reference to examples. In order to confirm the effect, an animal experiment with rats and a clinical experiment with human subjects targeting hypertensive patients were performed.

[1:動物(ラット)実験における実験材料及び実験方法]
この実験の為に、下記の本発明の実施例1と、実施例1の効果を確認するために、比較例1乃至比較例3を作成して実験した。
実施例1及び比較例1乃至3の組成は次のようなものである。
[1: Experimental materials and experimental methods in animal (rat) experiments]
For this experiment, in order to confirm the effects of Example 1 and Example 1 of the present invention described below, Comparative Examples 1 to 3 were created and experimented.
The compositions of Example 1 and Comparative Examples 1 to 3 are as follows.

実施例1の成分配合比率を[表1]に示す。
(表1)実施例1の成分配合比率(比率は重量%)
本件ラフマエキス(主剤)* 14%(ラフマエキス35mg含有)
甘草エキス(主剤) 10%
イチョウ葉エキス(主剤) 10%
ビール酵母 10%
デキストリン 44%
結晶セルロース 10%
蔗糖脂肪酸エステル 2%
計(錠)250mg 100%
The component blending ratio of Example 1 is shown in [Table 1].
(Table 1) Component mixing ratio of Example 1 (ratio is% by weight)
Raffma extract (main agent) * 14% (containing 35 mg of Raffa extract)
Licorice extract (main agent) 10%
Ginkgo biloba extract (main agent) 10%
Beer yeast 10%
Dextrin 44%
Crystalline cellulose 10%
Sucrose fatty acid ester 2%
Total (tablet) 250mg 100%

なお、実施例1で使用したラフマエキスは中国新疆地区特産のラフマ葉を使用、超音波抽出法でエキスを抽出したものである。特異な有効成分としては、今までの市販のラフマエキスで確認されたものは、イソクェルシトリン(isoquercitrin)一種類のみであるが、本実施例で使用したラフマエキスのなかに、イソクェルシトリン(isoquercitrin)6重量%とクェルセチン(quercetin)0.3重量%という二つ物質が高含量で検出された。このイソクェルシトリン(isoquercitrin)とクェルセチン(quercetin)、特に、クェルセチン(quercetin)は細動脈平滑筋を拡張する作用があるとされている。
後述する比較例2の市販のラフマエキスの有効成分には、クェルセチンの含有が確認できなかった。
また、主剤以外のビール酵母は消化系に良いとミネラル豊富という作用のため、混合し、他の三種類の成分は、錠剤を形成するため賦形剤として、また主剤に干渉しない原料を選んで使われている。
The luffa extract used in Example 1 was obtained by using a luffa leaf specially produced in Xinjiang, China, and extracting the extract by an ultrasonic extraction method. As a specific active ingredient, only one kind of isoquercitrin has been confirmed in the commercially available rafma extract so far. Among the rafma extracts used in this example, an isoquer is used. Two substances, 6% by weight of citrin and 0.3% by weight of quercetin, were detected in high content. This isoquercitrin and quercetin, particularly quercetin, is said to have an action of expanding arteriole smooth muscle.
It was not possible to confirm the content of quercetin in the active ingredient of the commercially available rafma extract of Comparative Example 2 described later.
Also, beer yeast other than the main ingredient is mixed with it because it is good for digestive system and rich in minerals. For the other three ingredients, select ingredients that do not interfere with the main ingredient as excipients to form tablets. It is used.

(比較例1)
(表2)比較例1(ラフマエキスのみ)の成分配合(比率は重量%)
本件ラフマエキス 20%(ラフマエキス50mg含有)
ビール酵母 10%
デキストリン 58%
結晶セルロース 10%
蔗糖脂肪酸エステル 2%
計(錠)250mg 100%
(Comparative Example 1)
(Table 2) Composition of Comparative Example 1 (Rahma extract only) (ratio is% by weight)
Raffa extract 20% (Raffma extract 50mg included)
Beer yeast 10%
Dextrin 58%
Crystalline cellulose 10%
Sucrose fatty acid ester 2%
Total (tablet) 250mg 100%

(比較例2)
(表3)比較例2(市販ラフマエキス:クェルセチンの含有が確認できないもの)の成分配合(比率は重量%)
市販ラフマエキス(主剤)* 20%(市販ラフマエキス50mg含有)
甘草エキス(主剤) 10%
イチョウ葉エキス(主剤) 10%
ビール酵母 10%
デキストリン 38%
結晶セルロース 10%
蔗糖脂肪酸エステル 2%
計(錠)250mg 100%
(Comparative Example 2)
(Table 3) Ingredients of Comparative Example 2 (commercially available rafma extract: quercetin cannot be confirmed) (ratio by weight)
Commercially available rafma extract (main ingredient) * 20% (containing 50 mg of commercially available rafma extract)
Licorice extract (main agent) 10%
Ginkgo biloba extract (main agent) 10%
Beer yeast 10%
Dextrin 38%
Crystalline cellulose 10%
Sucrose fatty acid ester 2%
Total (tablet) 250mg 100%

(比較例3)
(表4)比較例3(偽薬:無処置の対照群)の成分配合比率
生理食塩水 100%
(Comparative Example 3)
(Table 4) Composition ratio of Comparative Example 3 (placebo: untreated control group) Saline 100%

上記の実施例1の投入量を変えた2例と、比較例1乃至3について動物実験を行った。以下にその詳細を説明する。   Animal experiments were carried out on two cases in which the input amount of Example 1 was changed and on Comparative Examples 1 to 3. Details will be described below.

(1)被験動物
Wistarラット、♂♀併用、体重200g前後。
(1) Test animal
Wistar rat, with acupuncture, weight around 200g.

(2)対象試薬
1)実施例1の錠剤、
2)比較例1(ラフマエキスのみ:和漢生薬研究所)、
3)比較例2 市販ラフマエキス(市販品)、
4)比較例3 生理食塩水のみ(対照群)
上記の1)〜3)の試薬を、生理食塩水で研磨して溶かし、80℃の保温水槽で4時間振動させてから、−30℃で凍結し、その後37℃の水槽で解凍する。この作業を三回繰り返した後、10分間遠心分離(1600rpm)をし、濾過した溶液を生理食塩水で0.2g/mlに希釈し、冷蔵で保存する。
(2) Target reagent 1) Tablet of Example 1
2) Comparative Example 1 (Rahma extract only: Wakayama Research Institute)
3) Comparative Example 2 Commercial Raffma Extract (commercially available product)
4) Comparative Example 3 Saline alone (control group)
The above reagents 1) to 3) are dissolved by polishing with physiological saline, vibrated in a warm water bath at 80 ° C. for 4 hours, frozen at −30 ° C., and then thawed in a water bath at 37 ° C. This operation is repeated three times, followed by centrifugation (1600 rpm) for 10 minutes, and the filtered solution is diluted to 0.2 g / ml with physiological saline and stored in the refrigerator.

(3)実験器具
実験に使用した器具は、腸間膜恒温貫流装置、RM−6300型生理記録機 (NIHON KODEN)、TIAC-I型恒速静脈注射機(HARVARD APPARATUS)、ZL301型微小循環測定機等である。
(3) Experimental instruments The instruments used in the experiment were the mesenteric transfusion device, RM-6300 type physiological recording machine (NIHON KODEN), TIAC-I type constant velocity intravenous injection machine (HARVARD APPARATUS), ZL301 type microcirculation measurement Machine.

(4)実験方法
腸間膜微小循環障害の状態を観察するが、その薬物治療は次のとおりである。
まず、実験前の2日からラットに水を供給するだけで絶食させ、20%ウレタンの5ml/kgをラットの腹腔注射で麻酔する。次いで、頸総動脈を分離し、血圧を記録し、大腿静脈を分離して、用意された生理食塩水を大腿静脈から恒速で注入する。
腹腔を2cmぐらい開け、回盲部の回腸を灌流台の上に広げて載せ、37度恒温のリンゲル液を灌流する。顕微鏡で細動脈、毛細血管、細静脈が全部揃っている視野を探し出し、正常な微小循環の映像を録画し、10%高分子デキストラン8mg/kgを静脈注射し、これからトロンビン0.2μ/kgを恒速静脈注射する。
注射して10分後に、微小循環の障害が現れる。すなわち、本動物模型の特徴は、高分子デキストランとトロンビンを静脈に注射した10分後、腸間膜に典型的な微小循環の障害が現れ、血流の速度と血液の灌流量は降下し、血圧も下がる。治療されていない動物の血圧は徐々に回復するが、微小循環の障害は一時間以上続いている。
(4) Experimental method The state of mesenteric microcirculation disorder is observed. The drug treatment is as follows.
First, the rats are fasted only by supplying water from the 2nd day before the experiment, and 5 ml / kg of 20% urethane is anesthetized by intraperitoneal injection of the rats. The common carotid artery is then separated, blood pressure is recorded, the femoral vein is separated, and the prepared saline is infused from the femoral vein at a constant rate.
Open the abdominal cavity about 2 cm, spread the ileum of the ileocecum on the perfusion table, and perfuse 37 ° constant temperature Ringer's solution. Under a microscope, the visual field with all the arterioles, capillaries, and venules is searched, a video of normal microcirculation is recorded, and 8% / kg of 10% polymer dextran is injected intravenously. Constant-speed intravenous injection.
Ten minutes after injection, disturbances of microcirculation appear. That is, the feature of this animal model is that after 10 minutes of intravenous injection of high molecular weight dextran and thrombin, typical circulatory disturbances appear in the mesentery, the blood flow rate and blood perfusion rate decrease, Blood pressure also decreases. Blood pressure in untreated animals gradually recovers, but microcirculatory disturbances persist for over an hour.

ここで実験を開始するが、実施例1−1としてラットの体重1Kgに対して140mg/kg、実施例1−2として同様に70mg/kg、比較例1の本件ラフマ含有のものを同様に100mg/kg、比較例2の市販ラフマ含有のものを同様に100mg/kgを静脈注射する。比較例3の対照群は同じ量の生理食塩水を与えられる。この結果は次の(5)で説明する。
被験ラットの群分けは、実施例1-1(140mg/kg)をn=7、実施例1-2(70mg/kg)をn=8、比較例1(本件ラフマ100mg/kg)をn=8、比較例2(市販ラフマ100mg/g)をn=8、比較例3(無処置生理食塩水:対照群)をn=7とした。
なお、前記高分子デキストランは上海ブドウ糖製造社の製品であり、トロンビンはSigma社の製品を使用し、使用する時は、生理食塩水で2μ/mlに希釈する。ウレタンは上海化学試薬購入供給公司付属工場の製品で、リンゲル液はpH7.4に使用する時に調剤する。
Here, the experiment is started. As Example 1-1, 140 mg / kg with respect to 1 kg body weight of the rat as Example 1-1, 70 mg / kg as in Example 1-2, and 100 mg of Comparative Example 1 containing the present Luma. In the same manner, 100 mg / kg of the one containing the commercially available Ruffa of Comparative Example 2 is intravenously injected. The control group of Comparative Example 3 is given the same amount of physiological saline. This result will be described in the following (5).
The groupings of the test rats were as follows: Example 1-1 (140 mg / kg) n = 7, Example 1-2 (70 mg / kg) n = 8, Comparative Example 1 (the Raffma 100 mg / kg) n = 8 8 and Comparative Example 2 (commercially available Raffa 100 mg / g) were n = 8, and Comparative Example 3 (untreated saline: control group) was n = 7.
The polymer dextran is a product of Shanghai Glucose Manufacturing Co., and thrombin is a product of Sigma. When used, it is diluted to 2 μ / ml with physiological saline. Urethane is a product of Shanghai Chemical Reagent Purchasing and Supply Factory, and Ringer's solution is dispensed when used at pH 7.4.

(5)実験結果
前(4)項で、微小循環血管の障害が現れた後、前記の実施例1-1、実施例1-2、比較例1、比較例2、比較例3を投与し 5、10、20、30、45、60分の血流状態を観察、録画し、微小血管の密度、口径、血流の速度などを測った。
[微小循環血管の血流速度変化率]
図1のグラフは、微小循環血管における血流速度変化率を表示したものであるが、投薬後の各時間帯に血流速度を測り、投薬前と比較し、変化率を計算する。実施例1−1(140mg/kg)を投与することによって血流の速度は顕著に速くなり、作用の維持時間は1時間以上であり、実施例1−2(70mg/kg)と比較例1(本件ラフマ100mg/kg)、比較例2(市販ラフマ100mg/kg)の血流の速度は速くなったが、30分を経過してから作用が弱くなった。それでも、実施例1−2(70mg/kg)のものは、比較例1、2に対して1時間経過時点で効果は優位である。 また、生理食塩水だけの比較例3の被験ラットには、血流速度の変化が現れなかった。
この結果、本実施例1は、実施例1−1や1−2のように投与量が異なっても、ラフマ単体や市販ラフマの比較例よりも毛細血管等の微小循環血管における血流速度の改善に効果のあることが判る。
(5) Experimental results In the previous section (4), after the microcirculatory blood vessel disorder appeared, the above-described Example 1-1, Example 1-2, Comparative Example 1, Comparative Example 2, and Comparative Example 3 were administered. The blood flow state at 5, 10, 20, 30, 45, and 60 minutes was observed and recorded, and the density, diameter, blood flow velocity, and the like of the microvessels were measured.
[Change rate of blood flow velocity in microcirculatory vessels]
The graph of FIG. 1 displays the rate of change in blood flow velocity in the microcirculating blood vessel. The rate of blood flow is measured at each time zone after medication, and the rate of change is calculated by comparison with that before medication. By administering Example 1-1 (140 mg / kg), the blood flow rate was remarkably increased, and the duration of action was 1 hour or longer. Example 1-2 (70 mg / kg) and Comparative Example 1 The blood flow velocity of (Raffma 100 mg / kg in this case) and Comparative Example 2 (commercially available Raffa 100 mg / kg) increased, but the effect became weak after 30 minutes. Nevertheless, the effect of Example 1-2 (70 mg / kg) is superior to Comparative Examples 1 and 2 after 1 hour. Further, no change in blood flow velocity appeared in the test rats of Comparative Example 3 containing only physiological saline.
As a result, even in the case of different doses as in Examples 1-1 and 1-2, the present Example 1 shows the blood flow velocity in the microcirculatory blood vessels such as capillaries as compared with the comparative example of Ruffa alone or commercially available Raffa. It turns out that it is effective for improvement.

[微小循環血管の血流量変化率]
図2のグラフは、微小循環血管における血流量変化率を表示したものであるが、試薬を投与前後の細静脈の血流速度と血管の内径を測り、計算式によって血流の量を割り出し、その時の平均血圧で割って微小循環血液流量の相対値が得られた。
実施例1−1(140mg/kg)を投与した群の血液流量は比較例3(対照群)より著しく増加した。実施例1−2(70mg/kg)を投与した群の血液流量は比較例3(対照群)より増加が見られたが、実施例1−1(140mg/kg)よりは小さいく、比較例1(本件ラフマ100mg/kg)の群も血流量の変化があるが、持続時間は実施例1−1や実施例1−2より短く、比較例2(市販ラフマ100mg/kg)の場合、作用は弱く、持続時間は更に短くなった。
この結果から、本実施例1は、実施例1−1や1−2のように投与量が異なっても、ラフマ単体や市販ラフマの比較例よりも微小循環血管における血流量は増加し改善に効果のあることが判る。
[Change rate of blood flow in microcirculatory vessels]
The graph of FIG. 2 displays the rate of change in blood flow in the microcirculatory blood vessel, but measures the blood flow velocity of the venule before and after administration of the reagent and the inner diameter of the blood vessel, and calculates the amount of blood flow by a calculation formula. The relative value of the microcirculatory blood flow was obtained by dividing by the mean blood pressure at that time.
The blood flow rate of the group to which Example 1-1 (140 mg / kg) was administered was markedly increased compared to Comparative Example 3 (control group). The blood flow rate of the group administered with Example 1-2 (70 mg / kg) was increased compared to Comparative Example 3 (control group), but smaller than that of Example 1-1 (140 mg / kg). Although the blood flow rate is also changed in the group of 1 (this case, Raffma 100 mg / kg), the duration is shorter than that of Example 1-1 and Example 1-2. Was weaker and the duration was even shorter.
From this result, even in the case of different doses as in Examples 1-1 and 1-2, this Example 1 improves the blood flow rate in the microcirculatory blood vessels compared with the comparative example of Ruffa alone or commercially available Raffa. It turns out that it is effective.

[微小循環血管の口径の変化率]
図3のグラフは、微小循環血管における口径の変化率を表示したものであるが、投与前後の微小血管口の口径が、投与前の径微小血管口径に対して、比較例3の対照群が平均12%縮小したのに対して、実施例1−2(70mg/kg)が10.5%、実施例1−1(140mg/kg)の微小血管の口径は投与前と比べて15%も拡大した、比較例1(本件ラフマ100mg/kg)は比較例2(市販ラフマ100mg/kg)群及び比較例3の対照群より改善されたが、実施例1−1や実施例1−2群より弱かった。
この結果から、本実施例1は、実施例1−1や1−2のように投与量が異なっても、ラフマ単体や市販ラフマの比較例よりも微小循環血管の口径は拡大する。
[Change rate of the diameter of microcirculatory vessels]
The graph of FIG. 3 displays the change rate of the caliber in the microcirculating blood vessel. The caliber of the microvascular orifice before and after administration is different from that before administration in the control group of Comparative Example 3. While the average was reduced by 12%, Example 1-2 (70 mg / kg) was 10.5%, and the diameter of the microvessel of Example 1-1 (140 mg / kg) was increased by 15% compared to before administration. Comparative Example 1 (Raffma 100 mg / kg) was improved over the Comparative Example 2 (commercial Raffa 100 mg / kg) group and the Comparative Example 3 control group, but weaker than the Example 1-1 and Example 1-2 groups. It was.
From this result, the diameter of the microcirculating blood vessel in Example 1 is larger than that of the comparative example of Ruffa alone or commercially available Raffa even if the dose is different as in Examples 1-1 and 1-2.

このように、ラットを対象にした実験では、実施例1(1−1,1−2)のものが、微小循環血管の血流速度変化率、血流量変化率、口径の変化率の全てで、比較例よりも優れた効果があることが判る。   As described above, in the experiments on rats, those of Example 1 (1-1, 1-2) are all the blood flow rate change rate, blood flow rate change rate, and caliber change rate of the microcirculation blood vessels. It can be seen that there is an effect superior to that of the comparative example.

[2:高血圧患者の血圧、微小循環血管への作用]
次に、高血圧患者の血圧、微小循環血管への作用の実験を行ったが、試薬は前述した本発明の実施例1の外に、ラフマエキスの組成を変えた本発明の実施例2、実施例3、及び、比較例4として、ラフマエキスを含有しない偽薬を作成して実験を行った。実施例2、実施例3、及び、比較例4の組成は次とおりである。
[2: Effects on blood pressure and microcirculatory blood vessels in hypertensive patients]
Next, experiments on blood pressure and microcirculatory blood vessels of hypertensive patients were conducted. In addition to Example 1 of the present invention described above, the reagent was changed to Example 2 of the present invention, in which the composition of Rahma extract was changed. As Example 3 and Comparative Example 4, a placebo containing no rough extract was prepared and tested. The compositions of Example 2, Example 3, and Comparative Example 4 are as follows.

(表5)実施例2の成分配合比率(比率は重量%)
本件ラフマエキス(主剤)* 10%(ラフマエキス25mg含有)
甘草エキス(主剤) 12%
イチョウ葉エキス(主剤) 12%
ビール酵母 10%
デキストリン 44%
結晶セルロース 10%
蔗糖脂肪酸エステル 2%
計(錠)250mg 100%
(Table 5) Component mixing ratio of Example 2 (ratio is% by weight)
Raffa extract (main ingredient) * 10% (Roughma extract 25mg)
Licorice extract (main agent) 12%
Ginkgo biloba extract (main ingredient) 12%
Beer yeast 10%
Dextrin 44%
Crystalline cellulose 10%
Sucrose fatty acid ester 2%
Total (tablet) 250mg 100%

(表6)実施例3の成分配合(比率は重量%)
本件ラフマエキス(主剤)* 25%(ラフマエキス62.5mg含有)
甘草エキス(主剤) 8%
イチョウ葉エキス(主剤) 8%
ビール酵母 10%
デキストリン 37%
結晶セルロース 10%
蔗糖脂肪酸エステル 2%
計(錠)250mg 100%
(Table 6) Component formulation of Example 3 (ratio is% by weight)
Raffma extract (main ingredient) * 25% (Roughma extract 62.5mg included)
Licorice extract (main agent) 8%
Ginkgo biloba extract (main ingredient) 8%
Beer yeast 10%
Dextrin 37%
Crystalline cellulose 10%
Sucrose fatty acid ester 2%
Total (tablet) 250mg 100%

(比較例4)
(表7)比較例4の成分配合(比率は重量%)
ビール酵母 10%
デキストリン 68%
結晶セルロース 20%
蔗糖脂肪酸エステル 2%
計(錠)250mg 100%
(Comparative Example 4)
(Table 7) Composition of Comparative Example 4 (ratio is% by weight)
Beer yeast 10%
Dextrin 68%
20% crystalline cellulose
Sucrose fatty acid ester 2%
Total (tablet) 250mg 100%

上記の実施例1乃至実施例3と、比較例4について実験を行った。以下に、その詳細を説明する。
(1)被験者
「WHO/ISH(世界保健機関/国際高血圧学会)高血圧管理1999年のガイドライン」により高血圧患者を診断し、120名患者を集め、無作為に治療群1、治療群2、治療群3と無処置の比較対照群に分けた。
治療群1には、実施例1の試薬一錠(ラフマエキス35mg含有)/回を、3回/日を投与する。
治療群2には、実施例2の試薬一錠(ラフマエキス25mg含有)/回を、3回/日を投与する。
治療群3には、実施例3の試薬一錠(ラフマエキス62.5mg含有)/回)を、3回/日を投与する。
対照群には、比較例4の偽薬を投与する。
なお、前記4群の患者は、すでに実験1ヶ月以上前から降圧剤を連続服用しており、顕著な血圧降下作用が見られていなかった。実験が始まっても同じ薬を服用し続ける。また、除外基準として、18才以下、或いは70才以上、二次性高血圧患者、妊娠或いは哺乳期の女性、肝臓、腎臓、造血系に重大な疾患がある患者、精神病、三ヶ月連続服用ができない人は除外した。
図4の[表8]に前記4群の患者(表8〜10中のnは患者数)の一般情況を示すが、著しい差がないことを確認した。
Experiments were conducted on Examples 1 to 3 and Comparative Example 4 described above. The details will be described below.
(1) Subjects Diagnosed for hypertension according to “WHO / ISH (World Health Organization / International Hypertension Society) 1999 Guidelines for Hypertension Management”, collected 120 patients, and randomly treated group 1, treatment group 2, treatment group Divided into 3 and untreated control group.
Treatment group 1 receives one tablet of the reagent of Example 1 (containing 35 mg of Raffa extract) / times 3 times / day.
In the treatment group 2, one tablet of the reagent of Example 2 (containing 25 mg of Raffa extract) / times is administered 3 times / day.
In the treatment group 3, one tablet of the reagent of Example 3 (containing Roughma extract 62.5 mg / time) is administered 3 times / day.
The placebo of Comparative Example 4 is administered to the control group.
The patients in Group 4 had already taken a hypotensive agent continuously for more than 1 month before the experiment, and no significant blood pressure lowering effect was observed. Continue to take the same medicine after the experiment begins. Also, as exclusion criteria, under 18 years old or over 70 years old, patients with secondary hypertension, pregnant or lactating women, patients with serious diseases in liver, kidneys, hematopoietic system, psychosis, can not take 3 consecutive months People were excluded.
[Table 8] in FIG. 4 shows the general situation of the four groups of patients (n in Tables 8 to 10 is the number of patients), and it was confirmed that there was no significant difference.

(2)実験方法
実験期間は12週で、4群に投与されている降圧剤は、カルシウム拮抗剤(Amlodipine Besylate)、変換酵素遮断剤(Benazepril)、β受容体遮断剤(Betaloc)の一種類或は数種類。対照群は降圧剤のみで、治療群1には実施例1(35mg)の1回1錠を3回/日、治療群2には実施例2(25mg)の1回1錠を3回/日、治療群3には実施例3(62.5mg)の1回1錠を3回/日を、併用して服用する。
そして、自覚症状の確認、血圧の測定と微小循環状態の検査(毛細血管の平均密度、入口口径、出口口径、血流速度などを測定、分析)などを行なった。
検査項目は、実験前後の血圧変化;微小循環状態の変化;自覚症状;徴候であり、判断基準は、中華人民共和国衛生部薬政局編集の「中薬(薬草)新薬の高血圧治療の臨床指導原則」に基づき判断し、顕著、有効、無効で表した。統計学処理はt検定或はカイ平方検定が行った。
(2) Experimental method The experimental period is 12 weeks, and the antihypertensive agent administered to Group 4 is one of calcium antagonist (Amlodipine Besylate), converting enzyme blocker (Benazepril), and β receptor blocker (Betaloc). Or several types. The control group was only an antihypertensive agent, the treatment group 1 was once a tablet of Example 1 (35 mg) 3 times / day, the treatment group 2 was once a tablet of Example 2 (25 mg) 3 times / day. In the treatment group 3, take 1 tablet of Example 3 (62.5 mg) at a time, 3 times / day in combination.
Then, subjective symptoms were confirmed, blood pressure was measured, and microcirculation was examined (average density of capillaries, inlet diameter, outlet diameter, blood flow velocity, etc. were measured and analyzed) and the like.
Test items are changes in blood pressure before and after the experiment; changes in the microcirculation state; subjective symptoms; signs. Judgment criteria are “Guidelines for clinical guidance on hypertension treatment of new drugs (herbal medicines), edited by the Department of Pharmacy, Ministry of Health, China. ”And expressed as prominent, valid, or invalid. Statistical processing was performed by t-test or chi-square test.

(3)実験結果
実験前後の4群の血圧の変化を図5の[表9]に示す。この[表9]から明らかなように、比較例4の偽薬投与後の対照群での血圧は、殆ど変化しないのに対して、実施例1〜3ではいずれも血圧は低下していることが判る。
また、試薬投与前後の4群の毛細血管状態の変化、特に、指先の爪上皮の毛細血管観察(特許第3025671号)によるループ状毛細管の密度、その血管の入口口径、出口口径、流速の変化を図6の[表10]に示す。この[表10]から明らかなように、比較例4の偽薬投与後の対照群でのループ密度は殆ど変化しないのに対して、実施例1〜3ではループ密度は高くなり、また、血管の入口口径や出口口径の広がり度合も各実施例は比較例4よりも大きい。
(3) Experimental result [Table 9] of Drawing 5 shows change of blood pressure of four groups before and after an experiment. As is clear from this [Table 9], the blood pressure in the control group after administration of placebo in Comparative Example 4 hardly changed, whereas in Examples 1 to 3, the blood pressure was decreased. I understand.
In addition, changes in the capillary state of the four groups before and after the administration of the reagent, in particular, changes in the density of looped capillaries by capillary observation of the nail epithelium of the fingertip (Patent No. 3025671), inlet diameter, outlet diameter, and flow velocity of the blood vessels Is shown in [Table 10] of FIG. As is clear from this [Table 10], the loop density in the control group after administration of the placebo in Comparative Example 4 hardly changed, whereas in Examples 1 to 3, the loop density increased, In each example, the degree of spread of the inlet diameter and the outlet diameter is larger than that of Comparative Example 4.

さらに、自覚症状・徴候の変化については、自覚症状・徴候:眩暈、頭痛、頭重、胸苦しい、不整脈、不眠、脱力感などは、「比較例4の対照群」では顕著、有効、無効の割合は、2例(6.5%)、18例(58.1%)、11例(35.4%)で総有効率は64.5%であるのに対して、「実施例1の治療群1」の顕著、有効、無効の割合は、3例(9.7%)、25例(80.6%)、3例(9.7%)、総有効率は90.3%であり、「実施例2の治療群2」の顕著、有効、無効の割合は、2例(6.7%)、21例(70%)、無効7例(23.3%)、総有効率は76.7%であり、「実施例3の治療群3」の顕著、有効、無効の割合は、2例(7%)、有効23例(82.1%)、無効5例(17.9%)、総有効率89.1%である。
このように、偽薬の比較例4の対照群に比べ、実施例1の治療群1、実施例3の治療群3の総有効率は非常に高く、比較例4の対照群と比べて顕著な差があった。実施例2の治療群2も比較例4の対照群により明らかな差があったが、治療群1、3より総有効率は低かった。
これら4群間には有意な差がある(p<0.05、治療群1、3と治療群2、治療群2と対照群の比較;p<0.01、治療群1、3と対照群の比較)。治療群1と3の薬効は同じレベルである。また、治療群1と3の間に有意な差はなかった。
Furthermore, regarding changes in subjective symptoms / signs, subjective symptoms / signs: dizziness, headache, headweight, chest pain, arrhythmia, insomnia, weakness, etc. In 2 cases (6.5%), 18 cases (58.1%) and 11 cases (35.4%), the total effective rate was 64.5%, whereas “the treatment group of Example 1” 1 ”marked, effective, invalid rate is 3 cases (9.7%), 25 cases (80.6%), 3 cases (9.7%), the total effective rate is 90.3%, The remarkable, effective and ineffective ratios of “treatment group 2 of Example 2” were 2 cases (6.7%), 21 cases (70%), 7 cases ineffective (23.3%), and the total effective rate was 76. The percentage of remarkable, effective and ineffectiveness of “treatment group 3 of Example 3” was 2 cases (7%), 23 cases effective (82.1%), 5 cases ineffective (17.9%) ) The total effective rate is 89.1%.
Thus, the total effective rate of treatment group 1 of Example 1 and treatment group 3 of Example 3 of the placebo compared to the control group of Comparative Example 4 is very high and is significantly higher than that of the control group of Comparative Example 4. There was a difference. The treatment group 2 of Example 2 was also clearly different from the control group of Comparative Example 4, but the total effective rate was lower than the treatment groups 1 and 3.
There is a significant difference between these four groups (p <0.05, treatment groups 1 and 3 and treatment group 2, treatment group 2 and control group comparison; p <0.01, treatment group 1, 3 and comparison group comparison) . Treatment groups 1 and 3 have the same level of efficacy. There was no significant difference between treatment groups 1 and 3.

以上のように、本発明のラフマエキス含有の各実施例は、血圧を降下させ、毛細血管の密度や血流速度等の血行を改善する毛細血管循環改善剤であることが確認された。
すなわち、ラット実験と高血圧臨床実験結果によって実施例1は、微小循環の改善作用がある。動物実験では、試薬による血液高凝集状態の微小循環障害に実施例1は毛細血管血流速度、血流量、血管口径への改善作用が見出され、比較例のラフマエキス単品より顕著である。なお、本件ラフマエキス自体の微小循環改善作用も、市販ラフマエキスより優れたことも確認された。
高血圧患者での臨床実験では、降圧剤を一ヶ月以上に投与されて、血圧のコントロールは悪い患者に実施例1(35mg)と実施例2(62.5mg)の各1錠を3回/日、12週連続投与したところ、患者の血圧、微小循環状態は比較例4の偽薬の対照群より明らかな改善が見られ、顕著な差があった。実施例2(25mg)の1錠を3回/日、12週連続投与された群も血圧低下と微小循環状態の改善が見られたが、治療群1より弱かった。治療群3と治療群1の間に顕著な差は無く、ラフマエキスの作用強度は適切な濃度と関係していることが判る。
ただし、本件ラフマエキスは、実施例2の10重量%以下では効果が少なく、14重量%(実施例1)以上の実施例3の25重量%にしても効果は顕著に向上しないので、経済上、生理学上、安全性の面から、最適には14重量%である。
また、イチョウの葉エキスも8重量%以下では効果が少なく、12重量%以上では同様の理由で好ましくなく、最適には実施例1の10重量%である。同様に、甘草エキスも8重量%以下では効果が少なく、12重量%以上では同様の理由で好ましく、最適には実施例1の10重量%である。
すなわち、イソクェルシトリンとクェルセチンの高含有ラフマエキスが10〜25重量%、前記イチョウの葉エキスが8〜12重量%、前記甘草エキスが8〜12重量%を混合すればよく、ラフマエキスはより好ましくは14〜25重量%である。
As described above, it was confirmed that each of the examples containing the Raffa extract of the present invention is a capillary circulation improving agent that lowers blood pressure and improves blood circulation such as capillary density and blood flow velocity.
That is, according to the results of the rat experiment and the hypertension clinical experiment, Example 1 has an effect of improving microcirculation. In animal experiments, Example 1 shows an improvement effect on capillary blood flow velocity, blood flow volume, and blood vessel caliber in the microcirculation disorder in the blood highly-aggregated state by the reagent, which is more remarkable than the Ruffa extract single product of the comparative example. In addition, it was confirmed that the effect of improving the microcirculation of the Raffa extract itself was superior to that of the commercially available Raffa extract.
In clinical experiments with hypertensive patients, antihypertensive drugs were administered for one month or longer, and patients with poor blood pressure control were given 1 tablet each of Example 1 (35 mg) and Example 2 (62.5 mg) 3 times / day, When administered continuously for 12 weeks, the patient's blood pressure and microcirculation were clearly improved from the placebo control group of Comparative Example 4, and there were significant differences. A group in which one tablet of Example 2 (25 mg) was administered 3 times / day for 12 weeks continuously showed a decrease in blood pressure and an improvement in microcirculation, but it was weaker than treatment group 1. There is no significant difference between treatment group 3 and treatment group 1, and it can be seen that the strength of action of Raffa extract is related to the appropriate concentration.
However, the present Luma extract is less effective at 10% by weight or less of Example 2, and the effect is not significantly improved even at 25% by weight of Example 3 of 14% by weight (Example 1) or more. From the viewpoint of physiological safety, it is optimally 14% by weight.
Ginkgo biloba extract is also less effective at 8% by weight or less, and 12% by weight or more is not preferable for the same reason, and is optimally 10% by weight of Example 1. Similarly, licorice extract is less effective at 8% by weight or less, preferably 12% by weight or more for the same reason, and optimally 10% by weight of Example 1.
That is, 10 to 25% by weight of a high-content raquema extract of isoquercitrin and quercetin, 8 to 12% by weight of the ginkgo biloba extract, and 8 to 12% by weight of the licorice extract may be mixed. More preferably, it is 14 to 25% by weight.

生薬投与による毛細血管本数の増加や入口、出口の拡張によって血圧降下作用が霊芝などについての研究が本発明者らによって発表されているが、本発明の実施例の血圧低下も毛細血管本数の増加、入口、出口の拡張によるものと思われる。
また、本実施例で使用したラフマエキスは他社の市販ラフマ製品と異なるところは、以下の3点があり、これが、本発明の実施例の作用に関与するものと思われる。
(1)本発明で使用したラフマエキスは中国新疆地区特産のラフマ葉を使用、超音波抽出法でエキスを抽出したものである。特異な有効成分としては、今まで他社に確認されたものは、イソクェルシトリン(isoquercitrin)一種類のみであるが、当社のエキスのなかに、イソクェルシトリン(isoquercitrin)6重量%と、クェルセチン(quercetin)0.3重量%という二つ物質が高含量で検出された。イソクェルシトリン(isoquercitrin)とクェルセチン(quercetin)、特にクェルセチン(quercetin)は細動脈平滑筋を拡張作用がある。当実験も同じことが確認された。なお、ラフマ葉エキスの有効成分の確認は、中国2005版薬典:国家薬典印鑑編によると羅布麻甲素(isoquercitrin)と羅布麻乙素(quercetin)に指定されている]
(2)本発明の実施例には、イソクェルシトリン(isoquercitrin)とクェルセチン(quercetin)以外に、甘草エキスの有効成分グリチルリチンと、イチョウ葉エキス有効成分テルペンラクトン(ギンコライドA,B,C,Jとビロバライド)、クェルセチン(quercetin)などが含まれているため、特にクェルセチン(quercetin)の相乗効果が現れているものと思われる。
(3)本発明の実施例の作用としては微小循環血管への改善効果(毛細血管本数の増加、入口と出口の拡張)があることが確認された。
The present inventors have published a study on the effect of lowering blood pressure due to the increase in the number of capillaries by the administration of crude drugs and the expansion of the entrance and exit, but the reduction in blood pressure in the examples of the present invention is also the number of capillaries This is probably due to an increase in the number of entrances and exits.
In addition, the rough extract used in this example differs from commercially available rough product from other companies in the following three points, which are considered to be involved in the operation of the example of the present invention.
(1) The Raffa extract used in the present invention is a product obtained by extracting the extract by the ultrasonic extraction method using a Raffa leaf specially produced in Xinjiang, China. As a unique active ingredient, only one kind of isoquercitrin has been confirmed so far by other companies, but our extract contains 6% by weight of isoquercitrin, Two substances, 0.3% by weight of quercetin, were detected in high content. Isoquercitrin and quercetin, especially quercetin, have a dilating action on arteriole smooth muscle. The same was confirmed in this experiment. In addition, confirmation of the active ingredient of the Lafuma leaf extract, China 2005 edition medicine Source: is specified According to the National Pharmacopeia seal ed. Apocynum Asakabutomoto (isoquercitrin) to Luo cloth Asaotsumoto (quercetin)].
(2) In addition to isoquercitrin and quercetin, examples of the present invention include licorice extract active ingredient glycyrrhizin and ginkgo biloba extract active ingredient terpene lactone (ginkgolide A, B, C, J And bilobalide), quercetin, and the like, and it seems that the synergistic effect of quercetin is particularly apparent.
(3) It was confirmed that the effect of the embodiment of the present invention was an improvement effect on microcirculating blood vessels (increase in the number of capillaries, expansion of the inlet and outlet).

以上の動物実験や臨床実験から、イソクェルシトリンを6重量%以上、とクェルセチンを0.3重量%以上をとを高含有するラフマ葉エキスとイチョウの葉エキスと甘草エキスとを混合したラフマ抽出成分を含有する実施例1乃至実施例3の毛細血管循環改善剤は、ラフマ葉の抽出成分を用いているので人体に安全であり、高血圧患者に対して血圧を降下する作用効果があり、微小循環血管である毛細血管の密度を高め、毛細血管での血流速度を速め、血流量を増やし、毛細血管の血管口径を拡げる等の改善作用があることが確認できた。
その組成比率も、好ましくは、本件のイソクェルシトリンとクェルセチンとを高含有ラフマ葉エキスが10〜25重量%、イチョウの葉エキスが8〜12重量%、甘草エキスが8〜12重量%を混合した毛細血管循環改善剤であり、最適値は、実施例1のように、本件のイソクェルシトリンとクェルセチンとを高含有ラフマ葉エキスがほぼ14重量%、イチョウの葉エキスがほぼ10重量%、甘草エキスがほぼ10重量%である。
なお、本発明の特徴を損なうものでなければ、上記の実施例に限定されるものでないことは勿論であり、本発明の実施例は三つ主成分(ラフマ、甘草、イチョウ葉エキス)をベースに、カルシウム(真珠の粉、かきの殻、動物の骨など)、黒焼き(真菌、竹、木など)、ギャバ、金針菜、棗、百合の根、蓮の実、クコシ、酸棗仁、合歓花、夜交藤、纈草(けっそう)、五加参、菩提樹(ぼだいじゅ)、当帰、杜仲、牡丹皮、茯苓などを混合してもよいことは勿論である。
From the above animal experiments and clinical experiments, Raffa mixed with Raffa leaf extract, Ginkgo biloba leaf extract and licorice extract containing 6% by weight or more of isoquercitrin and 0.3% by weight or more of quercetin. The capillary circulation improving agent of Examples 1 to 3 containing an extract component is safe for the human body because it uses an extract component of Rahma leaves, and has the effect of lowering blood pressure for hypertensive patients, It has been confirmed that there are improving effects such as increasing the density of capillaries, which are microcirculatory vessels, increasing the blood flow velocity in capillaries, increasing the blood flow volume, and expanding the diameter of capillaries.
The composition ratio is preferably 10 to 25% by weight of the rafuma leaf extract high in the present case of isoquercitrin and quercetin, 8 to 12% by weight of the ginkgo biloba extract, and 8 to 12% by weight of the licorice extract. As in Example 1, the optimal value for the improvement of capillary circulation was a mixture of approximately 14% by weight of the luffa leaf extract containing the present isoquercitrin and quercetin, and approximately 10% by weight of the ginkgo biloba extract. %, Licorice extract is approximately 10% by weight.
It should be noted that the present invention is not limited to the above-described embodiment as long as it does not impair the characteristics of the present invention, and the embodiment of the present invention is based on three main components (ruffa, licorice, ginkgo biloba extract). Calcium (pearl powder, oyster shells, animal bones, etc.), black baked (fungi, bamboo, trees, etc.), gabba, gold needle vegetables, potatoes, lily roots, lotus seeds, kokushi, soy sauce Of course, it is possible to mix night-going wisteria, Keiso, Gokasan, Bodaiju, Toki, Tochu, peony, and cocoon.

本発明の実施例と比較例の微小循環血管の血流速度変化率のグラフの図The figure of the graph of the blood-flow rate change rate of the microcirculation blood vessel of the Example and comparative example of this invention 本発明の実施例と比較例の微小循環血管の血流量変化率のグラフの図The figure of the graph of the blood flow rate change rate of the microcirculation blood vessel of the Example of this invention, and a comparative example 本発明の実施例と比較例の微小循環血管の口径の変化率のグラフの図The figure of the graph of the change rate of the diameter of the microcirculation blood vessel of the Example of this invention and a comparative example 本発明の実施例と比較例の4群患者の一般情況の比較の[表8]の図[Table 8] Diagram of Comparison of General Conditions of Group 4 Patients of Example and Comparative Example of the Present Invention 本発明の実施例と比較例の実験前後の血圧変化の比較の[表9]の図[Table 9] diagram of comparison of blood pressure change before and after experiment of Example and Comparative Example of the present invention 本発明の実施例と比較例の4群実験前後の毛細管状態の変化の[表10]の図 である。FIG. 10 is a table of [Table 10] showing changes in capillary state before and after the four-group experiment of an example of the present invention and a comparative example.

Claims (1)

イソクェルシトリンを6重量%以上、クェルセチンを0.3重量%以上の高含量を有するラフマ葉エキスを10〜25重量%と、イチョウの葉エキスが8〜12重量%と、甘草エキスが8〜12重量%とを混合したことを特徴とするラフマ抽出成分を含有する毛細血管循環改善剤。 Iso Beautique Le citrine 6 wt% or more, and 10 to 25% by weight of Lafuma leaf extract with a high content of more than 0.3% by weight quercetin, and 8-12 wt% ginkgo leaf extract, sweet grass extract A capillary circulation improving agent containing a Ruffa extract component, characterized by mixing 8 to 12% by weight.
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