CN1308955A - Natural composition for preventing and treating cardiovascular and cerebrovascular diseases and its application - Google Patents
Natural composition for preventing and treating cardiovascular and cerebrovascular diseases and its application Download PDFInfo
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Abstract
A composition for preventing and treating cardiovascular and cerbrovascular diseases by reducing cholesterol, triglyceride, blood pressure and sugar, and low-density lipoprotein and raising high-density lipoprotein contains Tardine substances generated by fungus, natto kinase, nm-class particles of 7 Chinese-medical materials including gynostemma pentaphyllum, notoginseng, red sage root, etc, and sugar tolerance factor.
Description
The present invention relates to prevent and treat the natural composition and the application thereof of cardiovascular and cerebrovascular disease.
Hypertension, coronary heart disease and apoplexy all are angiopathy, and about existing about 100,000,000 people of cardiovascular and cerebrovascular vessel patient of China, annual therefore class is died of illness about about 2,000 ten thousand people of the person of dying.
The lipid that contains in the blood mainly is a cholesterol.It is to cause atherosclerotic principal element, and certainly, triglyceride also has certain effect.Cholesterol has two classes: HDL-C and low-density lipoprotein cholesterol.Low-density lipoprotein cholesterol (deleterious cholesterol) accounts for 2/3, is to form atherosclerotic main component, and HDL-C (useful cholesterol) accounts for 1/3, can remove cholesterol from ductus arteriosus wall.The cholesterol source has two: one, comes by food, and the 2nd, by synthetic in the body.
Hyperlipidemia is meant Chylomicron in the blood plasma, very low density lipoprotein (VLDL), has a class or a few class concentration to surpass normal range in this four classes lipoprotein of middle lipoprotein and low density lipoprotein, LDL.It is that the lipid metabolism imbalance causes.It forms dispersive atheromatous plaque at the arterial wall inner membrance, causes angiostenosis, blood flow to be obstructed, and in other words hyperlipidemia is to form lipoprotein through a series of biochemical reactions, and phagocyte is engulfed this albumen in the blood vessel, forms thecacells, causes thrombosis.Atherosclerosis that Here it is.Atherosclerosis and hypertension reciprocal causation.Hypertension is atheromatous important pathogenic factors, and late period, extensive atherosclerosis can cause senile hypertension.Hypertension and atherosclerosis and then can to form with the fibrin be the thrombosis of main component.Thrombosis at cardia might cause myocardial infarction; Thrombosis in the brain position might cause apoplexy and cerebral hemorrhage.Blood vessel blockage more can cause senile dementia.Above-mentionedly allly all can cause the blood vessel ischemia, even downright bad, Here it is the main pathologic basis of cardiovascular and cerebrovascular disease.
Developed the medicine of a lot of treatment cardiovascular and cerebrovascular disease abroad, but owing to be chemosynthesis, so side effect is all very big.Domestic except chemosynthesis, also have Chinese herbal medicine and microorganism formulation, yet be mostly from single target, lessly take all factors into consideration.
These three kinds of diseases of hypertension, coronary heart disease and apoplexy are closely related, usually merge to exist.Prevent that this class disease should be at different onset mechanism, in different phase, different levels, the multiple measure of employing, integrated control.Before not forming cardiovascular and cerebrovascular disease, multipath prevents that the formation of hypertension, hyperlipidemia, hyperglycemia and thrombosis from being positive prevention; After forming, the multipath adjustment and bring high blood pressure down, blood fat, blood glucose and thrombosis is positive therapeutic.
Based on above-mentioned consideration, be not difficult to find out that any medicine all has certain limitation, can not arrive by the face mask.Have only each medicine speciality of performance, science compatibility, mutual supplement with each other's advantages just can be played the effect of integrated control.
The food-grade microorganisms monascus can be produced the key enzyme 3-hydroxyl-3-methylglutaryl coenzyme A A reductase that suppresses synthetic cholesterol; The food stage yeast can be produced the sugar tolerance factor GTF of blood sugar lowering and blood fat reducing; The food stage Bacillus natto can be produced the nattokinase of thrombus dissolving; Chinese herbal medicine Herb Gynostemmae Pentaphylli etc. can reduce cerebral vascular resistance, suppress thrombosis.The elite part science compatibility of food-grade microorganisms preparation and pure natural Chinese herbal medicine, make compound preparation and can be used for the integrated control cardiovascular and cerebrovascular disease.
The statins material is that (3-hydroxyl-3-methylglutaryl coenzyme A, the strong inhibition agent of reductase HMG-CoA) are the effective ingredient of blood fat reducing to the cholesterol that produced by the fermentation of Monas cuspurpureus Went or the aspergillosis rate-limiting enzyme in synthetic.Monascus anka Nakazawa et sato also has certain hypotensive effect, and its active ingredient that brings high blood pressure down can be water-soluble, and molecular weight may be below 3000.The tunning of monascus also has the effect that suppresses tumor growth.Monas cuspurpureus Went is that (Li Gailing, Zhang Mao is good etc.: Monas cuspurpureus Went prospect U.S.'s " science " 1997 second phases of magazine Chinese translation (Sichuan, Chongqing)) for safety non-toxic to human body.
Nattokinase (nattokinase) is a kind of bacillus subtilis protein kinases, is a kind of serine protease that is produced by natto bacillus subtilis (Bacillus subtilis/natto) in the natto sweat.Nattokinase has fibrinolytic, can treat and prevent thrombotic disease, and it also can activate intravital plasminogen, thereby increases the amount and the effect of endogenous fibrinolysin.(Huang Zhili etc., nattokinase, the chemistry 2,000 20 (2) 82 of life).
GTF (Glucose Telerance Factor) is a kind of sugar tolerance factor that is generated by yeast assimilation trivalent chromium.It keeps normal blood sugar level except participating in carbohydrate metabolism in the human body, also influences intravital lipid metabolism, keeps the normal serum albumin cholesterol levels of human body, has the effect of blood lipid regulation.Clinical verified, chromium has stable glycosuria patients blood glucose level, the effect of mitigation symptoms.Can obviously reduce serum cholesterol to cardiovascular patient, improve high density lipoprotein, alleviate effects (Zheng builds the celestial functional food .1997 of China Light Industry Press) such as arteriosclerosis symptom.
Herb Gynostemmae Pentaphylli is that the natural medicine of both can doing has the plant that can do the function food additive, is used for anti-platelet aggregation already clinically, blood fat reducing, blood sugar lowering, the liver protecting, cardiovascular and cerebrovascular diseases such as raise immunity (Makin happiness etc., modern Chinese medicine pharmacology handbook.Chinese Medicine publishing house, 182 pages 1998).
The object of the present invention is to provide a kind of natural composition of preventing and treating cardiovascular and cerebrovascular disease, several drugs is worked in coordination, and reaches better therapeutic effect.
The object of the present invention is to provide medicine and the Application in Food of said composition at preparation treatment and prevention blood cerebrovascular disease.
The compositions of control cardiovascular and cerebrovascular disease of the present invention, comprise by mycetogenetic statins material, the nattokinase that fungus and antibacterial are produced when producing Semen Sojae Preparatum, one or more are selected from Herb Gynostemmae Pentaphylli, Radix Notoginseng, Radix Salviae Miltiorrhizae, Folium Ginkgo, Radix Puerariae, Rhizoma Chuanxiong, the nano_scale particle of Flos Carthami and Fructus Crataegi, sugar tolerance factor with the yeast generation, more than in four kinds two kinds, three kinds or four kinds, wherein in described compositions, the parts by weight of statins material are 1-15 part, Herb Gynostemmae Pentaphylli is 200-800 part, Radix Notoginseng is 0-600 part, Radix Salviae Miltiorrhizae is 0-600 part, Folium Ginkgo is 0-600 part, Radix Puerariae is 0-600 part, Rhizoma Chuanxiong is 0-600 part, Flos Carthami is that 0-600 part and Fructus Crataegi are 0-600 part, the parts by weight of sugar tolerance factor are 0.01-0.1 part, and the consumption of nattokinase is 1000-10000U in described compositions.
In the present invention, the bacterium that produces the statins material can be a Monascus anka Nakazawa et sato, also can be aspergillosis.Kinases can also can be the associated kinase with the molecular biology method clone from the bacillus cereus and the mycete that produce Semen Sojae Preparatum.Sugar tolerance factor can be by the complex GTF that contain organic chromium of yeast through fermenting and assimilating trivalent chromium and obtain.The statins material comprises that the Lip river cuts down its spit of fland (Lovastatin), suffering and cut down its spit of fland (Simvastatin), west and cut down its spit of fland (Cerivastatin), U.S.A and cut down its spit of fland (Mevastatin), generally cut down in its spit of fland (Pravastatin) one or more.
The nano_scale particle of Herb Gynostemmae Pentaphylli, Radix Notoginseng, Radix Salviae Miltiorrhizae, Folium Ginkgo, Radix Puerariae, Rhizoma Chuanxiong, Flos Carthami, Fructus Crataegi is for adopting the nano_scale particle of conventional nanotechnology preparation, the wherein nano_scale particle of preferred Herb Gynostemmae Pentaphylli.
In the present invention, its spit of fland is cut down, the preferred nattokinase of kinases, the preferred Herb Gynostemmae Pentaphylli extract of Chinese medicine, sugar tolerance factor preferred chromium yeast in the Lip river of the preferred Monas cuspurpureus Went generation of statins material.
In the present invention, according to different objects, this compound preparation can have the variation of various combination and dosage, as statins+chromium yeast, statins+nattokinase, statins+Herb Gynostemmae Pentaphylli, statins+Herb Gynostemmae Pentaphylli+nattokinase, statins+chromium yeast+Herb Gynostemmae Pentaphylli, statins+chromium yeast+nattokinase, statins+chromium yeast+nattokinase+Herb Gynostemmae Pentaphylli.
In compositions of the present invention, dosage range every day of every kind of medicine is statins 1-50mg/ day, GTF 10-200 μ g/ day, Herb Gynostemmae Pentaphylli 0.5-10g/ day, nattokinase 5000-100000u/ day.
Compositions of the present invention can be made various regular dosage forms, for example liquid preparation, capsule etc.Compositions of the present invention can also comprise the acceptable conventional adjuvant of any pharmacy.When making capsule, statins, chromium yeast and Herb Gynostemmae Pentaphylli can mix encapsulated, and its natto can be encapsulated in addition, also can be sub-packed in a capsule by four kinds of one-tenth.
With above four kinds of drug combinations, the pharmacological action of four kinds of medicines is complemented each other, effect obviously is better than every kind of medicine list and uses.
Compositions of the present invention also can be made functional food.
Compositions of the present invention is used to prepare the medicine and the food of treatment and prevention blood cerebrovascular disease.Its disease preventing and treating and health care also can be used for diabetes except that being used for the blood cerebrovascular disease.
The production of production technology 1. Monas cuspurpureus Went (its spit of fland is cut down in the Lip river):
Selected rice cooks after the immersion, and with the bacterial classification inoculation of slant activation, cultivation and fermentation is dried then, pulverizes, and measures the content that its spit of fland is cut down in the Lip river, and is standby.2. the production of natto (nattokinase):
Selected Semen sojae atricolor, the steaming and decocting of water logging bubble back, with the bacterial classification inoculation of slant activation, cultivation and fermentation then, maturation is measured the activity of nattokinase, and is standby.3. chromium yeast (GTF): available from section's fermentation engineering portion 4. Herb Gynostemmae Pentaphyllis in the Institute of Microorganism, Academia Sinica: Chinese Academy of Sciences's low temperature center 5. capsulations:
Its spit of fland (Hongqu powder (red colouring agent)), Herb Gynostemmae Pentaphylli, GTF (chromium yeast) and nattokinase mix homogeneously are cut down in the Lip river, and encapsulated, the packing of product obtains finished product.
Embodiment 1: the nattokinase preparation 1) preparation of natto
Bacterial strain Bacillus subtilis natto (Bacillus bultilis/natto)
Culture medium: Lb culture medium
Bacterial strain activates on the inclined-plane in advance, inserts fluid medium, incubated overnight then.
Semen Glycines processing: warm water soaking 12 hours, moisture about 45%, in pressure cooker with
1kg/cm
2Steaming and decocting is 1 hour under the pressure, is cooled to 30-35 ℃.
Fermented soybean: the strain of incubated overnight is inserted in the Semen sojae atricolor after the steaming and decocting, connect the bacterium amount and be
8%, 30 ℃ and 95% humidity bottom fermentation 48 hours, cryopreservation.2) preparation of nattokinase extract
Get natto 100g, add normal saline 5000ml, spend the night at dipping below 10 ℃.With
5000 left the heart 30 minutes, discarded precipitation, collected supernatant, added the sulfur ammonium to saturation
60%, after fully stirring, put refrigerator overnight, left the heart 30 minutes with 5000, it is heavy to collect
Form sediment, dialysis desalting leaves the heart with 5000 again, gets supernatant, obtains nattokinase and slightly carries
Liquid, lyophilization obtains the nattokinase powder.
Embodiment 2:
The Lip river is cut down the powder of its spit of fland (L) (Beijing biochemical-pharmaceutical factory), nattokinase (N) (embodiment 1 preparation), Herb Gynostemmae Pentaphylli (J), Semen Ginkgo (Y) (Chinese Academy of Sciences low temperature center), chromium yeast (G) (fermentation engineering portion of Institute of Micro-biology of the Chinese Academy of Sciences), ratio according to following table, mix, add granulations such as starch, Icing Sugar, encapsulated.
Experimental example 1: the zoopery of its spit of fland, Herb Gynostemmae Pentaphylli and GTF is cut down in the Lip river
| Medicine | Consumption |
| ????L+J | ????5g+600g |
| ????L+G | ????5g+40mg |
| ????L+N | ????5g+2000000U |
| ????J+G | ????600g+40mg |
| ????L+J+G | ????5g+600g+40mg |
| ????L+J+G+N | ????5g+600g+40mg+2000000U |
| ????L+J+G+N+Y | ??5g+600g+40mg+2000000U+400g |
With hypercholesterolemia and lipid forage feed rat, make it to form experimental hyperlipemia, give given the test agent simultaneously, the 14th day and blood sampling in 28 days of experiment, the formation of determination experiment animal serum T-CHOL (TC), triglyceride (TG), HDL-C (HDL-C) and low density lipoprotein, LDL (LDL-C).1. materials and methods
1) given the test agent: its spit of fland (L) (Beijing biochemical-pharmaceutical factory), nattokinase (N) are cut down in the Lip river
(embodiment 1 preparation), nanoscale Herb Gynostemmae Pentaphylli microgranule (D) (Chinese Academy of Sciences low temperature center),
Chromium yeast (G) (fermentation engineering portion of Institute of Micro-biology of the Chinese Academy of Sciences)
2) laboratory animal: provide wister rat by Chinese Academy of Medical Sciences's animal center, body weight
200±25g。
3) high lipid food: basestocks 93.8%, cholesterol 1%, Adeps Sus domestica 5% and sodium cholate
0.2％。
4) instrument and reagent: spectrophotometer, kyoto, Japan is made SHIMADZU; Cholesterol
Chemical reagents corporation provides by Beijing; Sodium cholate (cattle) is by Haidian, Beijing microbiological culture media system
Product factory provides; Serum total cholesterol (TC), triglyceride (TG), high density lipoprotein gallbladder are admittedly
Alcohol (HDL-C), low-density lipoprotein cholesterol (LDL-C) are measured test kit, by Beijing
The middle biological engineering High-tech company of giving birth to provides.
5) experimental technique:, promptly exist according to " health food function assessment assessment process and detection method "
Rat fed normal feedstuff 10 days under the environment of experiment, got a blood then, with enzymatic assays
TC, TG, HDL-C, LDL-C observation index normal value are according to blood lipid level, to greatly
Mus carries out random packet, 10 every group.
Begin each group (10 every group) animal from formal experiment and change hello high lipid food, rat is irritated and feeds different samples simultaneously, carries out continuously 28 days once a day, and high fat matched group is fed the normal saline with volume.By the eyes blood sampling, measure every blood lipids index after 14 days and 28 days.2. experimental result
The result judges: when hyperlipemia model was set up, TC, TG, HDL-C, LDL-C were respectively
When any one is positive in the item index, can think that all this given the test agent has adjusting
The effect of blood fat.
Positive judgement: 1. compare with the hyperlipidemia model group, difference has significance, preferably presents dose-effect relationship.
2.TC decline＞10%, TG decline 15%, HDL-C rising 4mg/dl
Each component of table 1. and prescription are to the influence of rat fat
*Compare P＜0.05 significant difference with high fat matched group
*With high fat matched group relatively P＜the 2nd group of L of 0.01 difference highly significant the 3rd group of J of effect of TG and LDL-C being had a highly significant to TC and remarkable the 4th group of G of TG effect to HDL-C and LDL-C effective the 8th group (L+J+G) to TC, TG, HDL-c and LDL-C have good effect experimental example 2: the blood coagulation resisting function of external nattokinase anticoagulant and thrombolytic effect 1. nattokinase
| Sample component and dosage | TC(mg/dl) | TG(mg/dl) | HDL- C(mg/dl) | LDL- C(mg/dl) |
| 1. water 2.L (2mg) 3.J (0.1g) 4.G (15 μ g) 5.L (2mg)+J (0.1g) 6.L (2mg)+G (15 μ g) 7.J (0.1g)+G (15 μ g) 8.L (2mg)+J (0.1g)+G (15 μ g) | ?190.5+51 ?142.3+45 ?100.2+20.8 **?148.8+35.2 ?126.4+32.5 *?164.8+40.2 ?159.2+43.5 ?65.4+21.2 ** | 182.6+50 102.3+21 **104+45.2 *113.9+45 *104.5+41.6 *140.5+24.8 127.8+24.5 110.6+24.6 * | ?15.6+3.1 ?16.5+5.2 ?15.4+4.2 ?20+4.8 **?47.8+28.9 *?45.8+29.8 **?23.8+29.4 **?46.5+27.5 ** | ?65.2+21.3 ?16.2+16.4 **?38.6+15.2 ?54.2+12.3 ?41.5+26.8 ?34.2+11.5 *?44.6+11.8 ?18.1+14.6 ** |
Get nattokinase crude extract and each 0.1ml of phosphate buffer of embodiment 1, put into two test tubes respectively, respectively add 1ml intravenous rabbit blood and observe clotting time.The results are shown in following table:
The external clotting time of table 2
| Handle | Clotting time | ||||
| 5 minutes | 10 minutes | 60 minutes | 90 minutes | ||
| Add the natto kinases | 1 | + | ++ | ||
| 2 | + | ++ | |||
| 3 | + | ++ | |||
| Add phosphate buffer | 1 | + | ++ | ||
| 2 | + | ++ | |||
| 3 | + | ++ | |||
+: just shown blood coagulation ++: blood coagulation fully
Find out that by table nattokinase has tangible blood coagulation resisting function.2. nattokinase is to the dissolution of clot
Get intravenous rabbit blood 5ml, put in vitro, after the natural coagulation, take out clot and be cut into little, blot with filter paper, weigh, divide and put two in vitro, add each 0.5ml of natto kinases crude extract and phosphate buffer respectively, after 24 hours, the residue clot blots weighs 39 ℃ of insulations.The results are shown in following table.
The effect of table 3. nattokinase haemolysis piece
| Handle | Clot weight in wet base (mg) before the dissolving | Dissolving back clot weight in wet base (mg) | Dissolution rate % |
| Nattokinase | 85.56 | ?6.55 | ?92.34 * |
| Phosphate buffer | 84.65 | ?72.43 | ?14.43 |
*Compare P＜0.01 with phosphate buffer
Claims (9)
1. compositions of preventing and treating cardiovascular and cerebrovascular disease, comprise by mycetogenetic statins material, the nattokinase that fungus and antibacterial are produced when producing Semen Sojae Preparatum, one or more are selected from Herb Gynostemmae Pentaphylli, Radix Notoginseng, Radix Salviae Miltiorrhizae, Folium Ginkgo, Radix Puerariae, Rhizoma Chuanxiong, the nano_scale particle of the Chinese crude drug of Flos Carthami and Fructus Crataegi, sugar tolerance factor with the yeast generation, more than in four kinds of materials two kinds, three kinds or four kinds, wherein in described compositions, the parts by weight of statins material are 1-15 part, Herb Gynostemmae Pentaphylli is 200-800 part, Radix Notoginseng is 0-600 part, Radix Salviae Miltiorrhizae is 0-600 part, Folium Ginkgo is 0-600 part, Radix Puerariae is 0-600 part, Rhizoma Chuanxiong is 0-600 part, Flos Carthami is that 0-600 part and Fructus Crataegi are 0-600 part, the parts by weight of sugar tolerance factor are 0.01-0.1 part, and the consumption of nattokinase is 1000-10000U in described compositions.
2. according to the compositions of claim 1, the fungus that wherein produces the statins material is Monascus anka Nakazawa et sato or aspergillosis.
3. according to the compositions of claim 1, wherein said kinases is from the bacillus cereus and the mycete that produce Semen Sojae Preparatum.
4. according to the compositions of claim 1, wherein said kinases applied molecular biology cloning process obtains.
5. according to the compositions of claim 1, wherein said sugar tolerance factor is for assimilating the complex sugar tolerance factor that contains organic chromium that trivalent chromium obtains by yeast through fermentation.
6. according to the compositions of claim 1, wherein said statins material comprises that the Lip river cuts down its spit of fland, suffering and cut down its spit of fland, west and cut down its spit of fland, U.S.A and cut down its spit of fland, generally cut down in its spit of fland one or more.
7. according to the compositions of claim 1, wherein said Chinese crude drug nano_scale particle is the Herb Gynostemmae Pentaphylli nano_scale particle.
8. according to the compositions of claim 1, cut down its spit of fland, nattokinase, chromium yeast, and Herb Gynostemmae Pentaphylli comprising the Lip river that Monas cuspurpureus Went produces.
9. any one compositions is preparing the medicine and the Application in Food for the treatment of and preventing the blood cerebrovascular disease among the claim 1-8.
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| CN103223033B (en) * | 2013-05-22 | 2015-01-28 | 武汉真福医药科技发展有限公司 | Novel natto health-care composite and preparation method and application thereof |
| CN103404757A (en) * | 2013-05-27 | 2013-11-27 | 胡安然 | Special diet for hyperglycemia patients |
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| CN107095974A (en) * | 2017-06-01 | 2017-08-29 | 中山大学 | A kind of hypoglycemic composition |
| CN109700006A (en) * | 2018-12-13 | 2019-05-03 | 深圳市淳睿贸易有限公司 | Natto enzyme composition |
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