CN1240393C - Application of astragalus root polysaccharide in preparation of antilipemic agent and health products - Google Patents
Application of astragalus root polysaccharide in preparation of antilipemic agent and health products Download PDFInfo
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Abstract
The present invention relates to the application of astragalus root polysaccharide to the preparation of medicines for reducing blood fat and health-care products. Researches show that astragalus root polysaccharide has the functions of reducing blood fat, lowering cholesterol and triglycerides and improving high-density lipoprotein; the astragalus root polysaccharide can prevent and treat cardiovascular and cerebrovascular diseases, such as atherosclerosis, coronary artery pathologic change, perivascular pathologic change, hyperlipemia, etc.
Description
Technical field
The present invention relates to the application of astragalus polysaccharides.Or rather, the present invention relates to the application of astragalus polysaccharides in preparation blood lipid-lowering medicine and health product, also relate to astragalus polysaccharides in preparation prevention and the medicine of treatment cardiovascular and cerebrovascular disease and the application in the health product.
Background technology
Medical research shows that lipid metabolism and cardiovascular disease are closely related, and hyperlipemia is that to cause that atherosclerotic one of the main reasons, particularly serum total cholesterol level increase be atherogenic dangerous index.Blood fat is the general name of each lipoids in the serum, and blood fat mainly comprises: cholesterol, triglyceride and phospholipid etc., also have other lipid of small-amount free fatty acid and minute quantity in addition, and comprise fatsoluble vitamin and steroid hormone etc.2/3rds forms with cholesteryl ester of cholesterol exist, and one of its excess-three branch is a free cholesterol.
Cholesterol is the important component of cell membrane and plasma lipoprotein, playing an important role in the flowability of keeping film with normally, is again the active raw materials of important biomolecule such as synthetic bile acid, steroid hormone (epinephrine 17-hydroxy-11-dehydrocorticosterone, androgen and estrogen) and vitamin D2.The cholesterol metabolism obstacle can cause that plasma cholesterol raises, and this is to form atherosclerotic a kind of risk factor, can cause cerebrovascular, coronary artery and peripheral angiopathy.So the disorderly relations with these diseases of cholesterol metabolism are one of current medical circle subject matter of attracting attention.And we are subjected to the remarkable cholesterol reducing of reagent astragalus polysaccharides, can prevent and treat atherosclerosis, cerebrovascular, coronary artery and peripheral angiopathy.With enzymic colorimetric (CHOD-PAP) measure T-CHOL (Total Cholesterol, TC).Principle is that reaction temperature is 37 ℃, with cholesterol ester hydrolase (CEH) cholesterol ester in the serum (CE) is hydrolyzed to free cholesterol (FC) and fatty acid earlier; Reuse cholesterol oxidase (COD) is oxidized to Ch-4-alkene-3-ketone with all FC in the serum, and produces H
2O
2The reaction (Trinder reaction) under peroxidase (POD) effect of the latter and 4-amino-antipyrine (4-AAP) and 4-chlorophenol generates red quinone imines, colorimetric determination under the 500nm wavelength.
Fat is made up of 1 molecule glycerol and 3 molecules of fatty acids, thus claim again trig lyceride (Triacylglycerol, TG) or triglyceride.The suggestion of border, native land NK does not re-use this title chemically clear and definite inadequately in one of back, but custom is referred to as.The rising of TG reduces the high density lipoprotein kind or composition changes, and produce the high density lipoprotein that is rich in TG, and the latter's reduction is relevant with atherosclerosis, and we be subjected to reagent astragalus polysaccharides substantial reduction in triglycerides.With enzymic colorimetric (GPO-PAP) measure triglyceride (Triglycerides, TG).Reaction temperature is 37 ℃, be glycerol and fatty acid with lipoprotein lipase (LPL) with the triglyceride hydrolysis in the serum earlier, under the effect of glycerol kinase (GK), glycerol and ATP reaction generate glycerol-3-phosphate and ADP, under the effect of phosphoglycerol oxidase (GPO), glycerol-3-phosphate is become dihydroxyacetone phosphate and H by dioxygen oxidation
2O
2, under peroxidase (POD) effect, H
2O
2Generate red quinone imines, colorimetric determination under the 500nm wavelength with 4-amino-antipyrine (4-AAP) and 4-chlorophenol reaction (Trinder reaction).
High density lipoprotein (HDL) can activate Lecithin-cholesterol acyltransferase. (LCAT), is the main vehicle that the extrahepatic tissue cholesterol is transported to liver, so its removing, plasma cholesterol and cholesteryl ester with plasma lipoprotein is relevant.We can say that HDL is a kind of antiatherogenic lipoprotein, the protection factor of coronary heart disease.Its protective effect and HDL special role in lipoprotein metabolism to coronary heart disease is undivided.It may shield by following mechanism: the HDL subclass that 1. contains APOE can be discerned the B1E receptor of LDL; And with LDL competition receptor, reduce absorption and the degraded of LDL; 2. HDL can be transferred to the cholesterol of peripheral tissues in liver and carries out metabolism, and in this cholesterol antiport, HDL is the carrier of cholesterol, and LCAT plays an important role in this process.This effect of HDL can prevent that cholesterol is at cell deposition; 3. APOC is provided, promotes the metabolism of CM, VLDL, plasma cholesterol is descended.4. HDL-C and prostaglandin (PGI
2) synthetic positive correlation, PGI
2Level raises, and can strengthen anticoagulant, and vasodilation is difficult for taking place atherosclerosis.And we are subjected to the remarkable high density lipoprotein increasing of reagent astragalus polysaccharides, fully activate Lecithin-cholesterol acyltransferase., are the main vehicle that the extrahepatic tissue cholesterol is transported to liver, can remove plasma lipoprotein, plasma cholesterol and cholesteryl ester.Measure HDL-C (High Density Lipoprotein Cholesterol with phosphotungstic acid-magnesium precipitate method, HDL-C), low density lipoprotein, LDL in the serum (LDL) and very low density lipoprotein (VLDL) (VLDL) are behind phosphotungstic acid-magnesium precipitate, supernatant is high density lipoprotein (HDL), its cholesterol level enzymatic assays.
At present, along with rapid economy development, great changes will take place for people's dietary structure, high heat food intake rates such as Animal fat increase, add the variation of the socio-psychological factors of rhythm of life due to accelerating, and hyperlipidemia population is increased, corresponding therewith, the sickness rate of cardiovascular and cerebrovascular disease raises.Though all kinds of fat-reducing medicaments arise at the historic moment, comprising as lipid-lowering statins (main cholesterol reducing, slight triglyceride reducing): lovastatin, simvastatin, pravastatin and fluvastatin; Cholic acid adsorbent (cholesterol reducing, triglyceride slightly raises) comprising: Kao Laixi amine and Kao Lai TEPA; Shellfish butanoic acid class lipid lowerers (main triglyceride reducing) comprising: fenofibrate, bezafibrate and lucky F are neat; Nicotinic acid class lipid lowerers (all effective to triglyceride reducing and cholesterol) comprising: nicotinic acid and acipimox.Though these medicines have effect for reducing fat, many side effect are also arranged, medical circle is making great efforts to develop the little fat-reducing medicament of side effect.It is reported that the polysaccharide that extracts has effect for reducing blood fat as laminarin, squash polyoses, sea grass polysaccharide, ulva polysaccharide and lycium barbarum polysaccharide from natural plants, but do not see that as yet astragalus polysaccharides has the relevant report of effect for reducing blood fat.The inventor is engaged in the comprehensive development and utilization research of Radix Astragali resource, study for a long period of time and a large amount of result of the tests show, astragalus polysaccharides has blood fat reducing function, and the effect of remarkable cholesterol reducing and triglyceride, high density lipoprotein increasing is arranged, and has finished the present invention on this basis.
Summary of the invention
One of the object of the invention provides astragalus polysaccharides in the medicine of preparation blood fat reducing and the application in the health product;
Two of the object of the invention provides astragalus polysaccharides in the medicine of preparation cholesterol reducing, triglyceride reducing and high density lipoprotein increasing and the application in the health product;
Three of the object of the invention provides astragalus polysaccharides in the medicine of preparation cholesterol reducing and the application in the health product;
Four of the object of the invention provides astragalus polysaccharides in the medicine of preparation triglyceride reducing and the application in the health product;
Five of the object of the invention provides astragalus polysaccharides in the medicine of preparation high density lipoprotein increasing and the application in the health product;
Six of the object of the invention provides astragalus polysaccharides in preparation prevention and the medicine of treatment cardiovascular and cerebrovascular disease and the application in the health product;
Seven of the object of the invention provides astragalus polysaccharides in preparation prevention with treat application in atherosclerotic medicine and the health product;
Eight of the object of the invention provides astragalus polysaccharides in preparation prevention and the medicine of treatment coronary artery pathological changes and the application in the health product;
Nine of the object of the invention provides astragalus polysaccharides in preparation prevention and the medicine of treatment peripheral angiopathy and the application in the health product;
Ten of the object of the invention provides astragalus polysaccharides in preparation prevention and the medicine of treatment hyperlipemia and the application in the health product.
The Radix Astragali is the dry root of leguminous plant Radix Astagali Astragalus membranaceus (Fisch.) Bge.Var.mongholicus (Bge.) Hsiao.Spring, Qiu Erji excavate, and remove fibrous root and root head, dry.This product is cylindrical, and what have has a branch, and the upper end is thicker, long 30～90cm, diameter 1～3.5cm.Surface light brown yellow or light brown brown have irregular vertical wrinkle or longitudinal furrow.Matter is hard and tough, frangibility not, and section fibrous is strong, and apparent pink colour, skin zone's yellow-white, woody part is faint yellow radial texture and crack.Feeble QI, it is little sweet to distinguish the flavor of, and that chews littlely has a beany flavor.The Radix Astragali has functions such as invigorating QI to consolidate the body surface resistance, diuresis poison holding.The astragalus root of spontaneous growth is cleaned, thinly sliced, dry, pulverize,, promptly get astragalus polysaccharides with the extraction of distilled water decocting in water, precipitate with ethanol, separation.To extraction of Astragalus Polysaccharides in Astragalus method of the present invention, its purity, molecular weight, composition, structure authentication method are made brief description below.
1. the preparation method of astragalus polysaccharides
The astragalus root of Inner Mongolia Autonomous Region spontaneous growth is cleaned, thinly sliced, dry, be ground into the end.The 750g Radix Astragali powder is poured in the 5000mL three-necked bottle, adds the 3000ml distilled water, insert 5000mL adjustable temperature control electric jacket, with the electronic stirring of JHS-1 electronic thermostatic blender, 70 ℃ following backflow 2-3 hour.Cool to room temperature filters.Filter cake is extracted 2 times according to the method described above with distilled water again.Merging filtrate is used the Rotary Evaporators concentrated extracting solution, until dense mucus, it is splashed into a large amount of dehydrated alcohol (ratio 1: precipitate 5-10), spend the night gradually.Abandoning supernatant, will precipitate centrifugal, again with resolution of precipitate in distilled water, concentrate this solution, to the utmost point dense, with its splash into a large amount of ethanol (ratio 1: precipitation 5-10), spend the night.With the astragalus polysaccharides that obtains precipitation, be dissolved in distilled water, steam residual ethanol, with liquid nitrogen or household freezer with it freezing after, freeze-dried with freezer dryer, obtain astragalus polysaccharides 60g, productive rate 8.0%.Use the same method and extract the 1400g Radix Astragali powder, obtain Radix Astragali raw sugar 170g altogether, productive rate 12.14%.The astragalus polysaccharides productive rate is at 8-12%.Total sugar amount 85-95%.
2. the purity of astragalus polysaccharides and molecular weight
Illustrate about astragalus polysaccharides purity: the astragalus polysaccharides that said here is precipitable macromole natural polysaccharide in the alcohol solvent, and its molecular weight generally is not less than 2000.Non-setting organic compound in alcohol solvent belongs to small molecular weight impurity.The purity of the astragalus polysaccharides that we extract is insoluble macromole (polysaccharide) in the ethanol.The Determination on content method of astragalus polysaccharides in the product is with soaked in absolute ethyl alcohol astragalus polysaccharides product 30 minutes, leaches polysaccharide then, evaporate to dryness ethanol filtrate, drying, weighs.Can obtain the weight of ethanol soluble substance.Astragalus polysaccharides purity meter formula is as follows:
Astragalus polysaccharides purity is average more than 96%, and purity range is at 95%-99%.
Illustrate about molecular weight: astragalus polysaccharides is a kind of natural polysaccharide, belongs to polymer substance.Polymer substance is consistent or close by structure, and the different a large amount of macromolecular compounds of molecular weight are formed.Therefore, polymer substance is different from micromolecule, and macromolecule does not have molecular weight accurately, has only mean molecule quantity (Mn).Mean molecule quantity can use gel permeation chrommatograph (GPC) to measure.The number-average molecular weight scope of the astragalus polysaccharides that we extract is 2-10 ten thousand.The astragalus polysaccharides of molecular weight minimum also is the polysaccharide that precipitates in ethanol.Small molecular sugar and micromolecule organic compound can not precipitate in ethanol.
Through elementary analysis, astragalus polysaccharides contains: C:40-42 (average 41.14); H:6.3-7.3 (average 6.77); N:2.0-3.0 (average 2.38).
3. the structure of astragalus polysaccharides is identified
Astragalus polysaccharides is as the natural macromolecule amylose of molecular weight ranges broad, and its molecular structure is very complicated, and is also not fully aware of at home and abroad at present.But to the water-soluble portion of astragalus polysaccharides, people have done a lot of researchs, and we have also done than systematic research work.
The main composition and the structure thereof of astragalus polysaccharides are 1, the 4-D-alpha-glucans.This composition accounts for more than 90% of total astragalus polysaccharides.The structure of astragalus polysaccharides is difficult to determine with simple physical chemistry method.All can not determine the structure of astragalus polysaccharides as means such as infrared spectrum, ultraviolet spectra, gas chromatogram, tlc analysis, also be difficult to use in determining of quality standard.At present best method be with the carbon-13 magnetic resonance collection of illustrative plates (
13C-NMR).See
13On the C-NMR collection of illustrative plates, carbon 1 characteristic peak of astragalus polysaccharides is between 98-100ppm.The strong peak and 1 of 6 C of astragalus polysaccharides, the 6-D-alpha-glucans
13The C-NMR collection of illustrative plates is identical substantially.The chemical potential (PPm) at the strong peak of 6 C of astragalus polysaccharides and glucosan is as follows: C1:98.93 C2:70.67 C3:72.67 C4:75.89 C5:71.03 C6:59.73.
Description of drawings
Fig. 1 is an astragalus polysaccharides
13The C-NMR collection of illustrative plates.
The specific embodiment
Further set forth the application of astragalus polysaccharides of the present invention in preparation blood lipid-lowering medicine and health product below by the test example, and astragalus polysaccharides is at preparation prevention and the medicine of treatment cardiovascular and cerebrovascular disease and the beneficial effect of the application in the health product.
Test example one. astragalus polysaccharides safety (toxicity) test
According to the study of tcm new drug guideline, astragalus polysaccharides has been carried out the chmice acute toxicity test observed, the pre-test result of animal shows, because astragalus polysaccharides does not have tangible toxicity, can't measure LD
50, therefore to being subjected to the reagent thing to carry out the mensuration of maximum dosage-feeding.
Experiment purpose: observe the acute toxic reaction and the death condition that are produced behind the mice lavage astragalus polysaccharides.
Test material: (1) is by reagent: astragalus polysaccharides is provided by this laboratory (University of the Inner Mongol's polymer chemistry and mongolian medicine institute).Take by weighing an amount of astragalus polysaccharides lyophilized powder during test and be made into the aqueous solution 0.108g/ml of the Cmax that can irritate stomach with distilled water, standby.(2) animal: Kunming kind white mice, 32, male and female half and half, body weight 21 ± 1.2g is provided by University of the Inner Mongol Animal Experimental Study center, 20～23 ℃ of laboratory temperatures, relative humidity 70%.
The prerun acute toxicity test
Get 12 of mices, male and female half and half, fasting 12h, can't help water, observe the disposable Cmax 0.1075g/ml of astragalus polysaccharides, maximum volume amount 0.8ml/20g body weight is given toxic reaction, body weight change and the death condition that is produced behind the mouse stomach, observe once every day, observed 7 days continuously, the result lists table 1, table 2 in, and experimental result shows that body weight gain is normal.Each organ, system's physiological reaction are normal, the avirulence performance.Viewing duration does not have 1 example death, and survival rate is 100%, should continue to increase dosage by rule and estimate lethal dose to finding out 100%, but be subjected to the quantitative limitation of the highest filling stomach volume, can't continue to increase dosage, can't accurately calculate median lethal dose(LD 50) LD yet
50Illustrate that astragalus polysaccharides is safe, nontoxic, is applicable to clinical.
Maximum dosage-feeding is measured
Ministry of Health of the People's Republic of China's provisions for new drugs approval points out that to the specification requirement of new drug toxicological study supplementary notes " the Chinese medicine preparation acute toxicity test as dense because of medicine or the administration volume is excessive, can't be measured LD
50The time maximum volume that can give under the Cmax that animal can accept carry out determination of acute toxicity, and can be in 24 hours oral repeatedly (two to four times), to observe the untoward reaction that (in seven days) are in a short time produced.
Get 20 of mices, be divided into matched group, administration group at random, 10 every group, male and female half and half.Animal fasting 12 hours can be irritated stomach Cmax 0.108g/ml with medicine to mice, irritates stomach 3 times in the dose 24h of maximum volume amount 0.8ml/20g body weight, and total dosage 13g/kg body weight is equivalent to 216 times (recommended drug amount 60mg/kg days) of recommended drug amount.Matched group is irritated capacity distilled water such as stomach.After giving mouse stomach, to issuable toxic reaction, body weight change and death condition, observe once every day, observed continuously 7 days.The result lists table 3, table 4 in, and experimental result shows viewing duration, and body weight gain is normal, the physiological reaction of each tract is normal, the avirulence performance, and none example is dead.Astragalus polysaccharides mouse stomach maximum dosage-feeding is 0.108g/20g, and 3 times on the 1st, total dosage is equivalent to recommend 216 times of consumption 60mg (astragalus polysaccharides)/kg body weight by body weight 13g/kg.Show that in the mouse experiment, astragalus polysaccharides does not have toxicity, clinical practice safe and reliable (＞200 times).More than two tests fully confirm that astragalus polysaccharidess are safe, nontoxic.So, can relievedly utilize astragalus polysaccharides developing food products, health product, medicine etc.
Table 1 astragalus polysaccharides is to the trial test body weight change list position of acute toxicity test in mice: g
| Time | Body weight (means standard deviation) | Death condition |
| Before the administration after the administration 1 day | 20.35±1.11 21.43±1.07 | Do not have |
| After the administration after the administration in 2 days after the administration in 3 days after the administration in 4 days after the administration in 5 days after the administration in 6 days 7 days | 22.36±0.97 23.27±0.99 23.33±0.79 24.89±0.62 26.46±0.94 27.46±1.00 | Do not have |
Mouse toxicity response situation after table 2 administration
| Tract | Inspection method | The toxicity performance |
| Maincenter and kinetic system abnormal motion neural reflex automatic nervous system secretion respiratory system gastronintestinal system skin and fur other | Reaction pupil nose stool color, the integrality of behavior to stimulating | Few moving in the administration one day after, normal no abnormality seen secretion has no the secretion breathing and frequency normally has no other various anomalies after always normal the no normal administration of afterwards activity |
Table 3 astragalus polysaccharides is to acute toxicity test in mice--the body weight change list position of-maximum dosage-feeding test: g
| Time | Matched group | The administration group | The P value | Death condition |
| Before the administration after the administration after the administration in 1 day after the administration in 2 days after the administration in 3 days after the administration in 4 days after the administration in 5 days after the administration in 6 days 7 days | 21.34±0.92 22.36±0.96 23.27±0.84 23.98±0.67 24.69±0.64 25.40±0.76 26.11±0.99 26.82±1.27 | 21.63±1.38 22.07±1.72 23.45±1.93 23.15±2.70 25.00±2.24 25.85±2.34 27.11±2.36 27.34±1.75 | 0.58 0.44 | Do not have |
Mouse toxicity response situation after table 4 administration
| Tract | Inspection method | The toxicity performance |
| Maincenter and kinetic system abnormal motion neural reflex automatic nervous system secretion respiratory system gastronintestinal system skin and fur other | Reaction pupil nose stool color, the integrality of behavior to stimulating | Activity increases rear minimizing in the administration one day after, and normal no abnormality seen secretion has no that secretion is breathed and the normal abdominal distension of frequency has no normally that other are various unusually after always normal normal the no normal administration of afterwards activity |
Test example two. the blood fat reducing drug effect test of astragalus polysaccharides
1 laboratory animal and material
Laboratory animal: secondary male Wistar whitewash mouse, body weight 170 ± 10g
(University of the Inner Mongol zooscopy center provides).
Experiment reagent: astragalus polysaccharides is extracted by this institute oneself;
The T-CHOL test kit is produced by Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.;
Product batch number: 180091, the card number: capital T20010069
The triglyceride test kit is produced by Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd.;
Product batch number: 220411, the card number: capital T20010069
Cholesterol is produced by Beijing chemical reagents corporation;
Product batch number: 020816
Sodium cholate is produced by Haidian District Beijing microorganism culturing mechanical goods factory;
Product batch number: 020726
Simvastatin is produced by Jiangsu Lianhuan Pharmaceutical Co., Ltd.;
Product batch number: 20020601
Yolk powder is by port, border, Dalian biochemical product factory
Product batch number: 801103
Experimental apparatus: PRONTO EVOLUTION full automatic biochemical apparatus (Italy produces):
TDL-5-A centrifuge (going up marine products);
The prescription of high lipid food:
Prescription 1 (the preventative administration model that tried): cholesterol 3%, Adeps Sus domestica 10%, sodium cholate 0.5%, normal feedstuff 86.5% (prescription: flour 20%, rice flour 10%, corn 20%, wheat bran 25%, bean material 20%, bone meal 2%, fish flour 2%, Sal 0.9%, vitamin 0.1%).
Prescription 2 (therapeutic is tried the administration model): cholesterol 1%, Adeps Sus domestica 10%, sodium cholate 0.2%, yolk powder 10%; Normal feedstuff 78.8% (prescription: flour 20%, rice flour 10%, corn 20%, wheat bran 25%, bean material 20%, bone meal 2%, fish flour 2%, Sal 0.9%, vitamin 0.1%).
2. the zoopery of astragalus polysaccharides prevention hyperlipidemia
Hyperlipidemia model and administration:Get 30 of rat, body weight 170 ± 10g, male, after feeding 3 days with the common standard feedstuff, be divided into 3 groups at random by body weight, 10 every group, 1 group is the high lipid food matched group; 2 groups of positive matched groups; 3 groups is the astragalus polysaccharides group; Administration began to feed every 20g/ of high lipid food days on the 1st day, irritated the stomach time: every morning 10:30.Grouping situation and respectively organize dosage and see Table 5.
Measure and observational technique: each organized gastric infusion 14 days, and fasting be can't help water 12 hours in the time of the 15th day, and the tail vein is got blood, adopted enzymic colorimetric to measure serum total cholesterol value and triglyceride value on full automatic biochemical apparatus.The gained data are carried out statistical procedures, represent with mean ± standard deviation, the significance of difference is judged with the T check.
The result:Calculated dosage every 5 days by the Mus body weight.Body weight change sees Table 6, and each group increases normally from 1,5,10,15 day body weight, no abnormal variation between each group of average weight, and nontoxic, the safety of proof astragalus polysaccharides.Experimental result is listed table 7,8,9,10 in.Table 7,8 shows that two groups of comparison blanks all have certain T-CHOL effect of falling, but do not have significant difference.Simvastatin group and matched group relatively P value compare the P value greater than astragalus polysaccharides and matched group, show that the T-CHOL effect of falling of astragalus polysaccharides is also better than positive control drug (simvastatin), but do not have significant difference.Table 9,10 shows, two groups more all have the effect of certain triglyceride reducing with blank, and there were significant differences.Simvastatin group and matched group relatively P value compare the P value less than astragalus polysaccharides and matched group, show that the triglyceride reducing effect of astragalus polysaccharides is good not as positive control drug (simvastatin), but do not have significant difference.
Table 5 grouping situation reaches respectively organizes dosage
| Group | 1 | 2 | 3 |
| Medicine dosage (mg/kg) (mg/Kg) | Contrast (H 2O) 60 | Positive control (simvastatin) 10 | Be subjected to reagent (astragalus polysaccharides) 60 |
Table 6 average weight change records (g)
| Group | Matched group | The simvastatin group | The astragalus polysaccharides group |
| The 1st day the 5th day the 10th day the 15th day | 163.7 206.0 237.1 249.7 | 163.2 199.0 221.5 236.9 | 164.0 205.3 223.2 243.5 |
The 15th day rat serum total cholesterol level measurement result (mmol/L of unit) after table 7 administration
| Matched group | The simvastatin group | The astragalus polysaccharides group | |
| No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 No. 7 No. 8 No. 9 No. 10 mean value standard deviations | 3.71 10.06 3.3 5.07 2.88 3.41 3.88 5.29 3.89 3.32 4.57 2.21 | 2.41 4.01 7.67 3.12 2.29 2.99 2.68 3.17 3.92 3.40 3.69 1.59 | 3.66 3.30 2.46 3.35 3.34 3.29 2.49 4.65 2.00 3.20 3.12 0.76 |
(mmol/L) analyzed in the influence (means standard deviation) of table 8 pair rat serum cholesterol
| Group | Animal example number (only) | Dosage | T-CHOL | The P value |
| Matched group simvastatin group astragalus polysaccharides group | 10 10 10 | 10mg/Kg body weight 60mg/Kg body weight | 4.57±2.21 3.69±1.59 3.12±0.75 | *0.282 **0.080 |
* simvastatin group and matched group are relatively: P＞0.05, * * astragalus polysaccharides and matched group compare: P＞0.05.
The 15th day rat serum triglycerides assay result (mmol/L of unit) after table 9 administration
| Matched group | The simvastatin group | The astragalus polysaccharides group |
| No. 1 No. 2 No. 3 No. 4 No. 5 No. 6 No. 7 No. 8 No. 9 No. 10 mean value standard deviations | 1.06 1.23 1.08 1.25 0.66 0.98 1.36 1.23 1.41 1.28 1.15 0.22 | 0.53 0.94 0.93 1.06 0.80 1.16 0.86 0.60 1.04 0.74 0.87 0.20 | 1.03 0.99 0.82 1.02 0.82 0.92 0.73 0.93 0.97 1.12 0.93 0.10 |
(mmol/L) analyzed in the influence (means standard deviation) of table 10 pair rat serum triglyceride
| Group | Animal example number (only) | Dosage | Triglyceride | The P value |
| Matched group simvastatin group astragalus polysaccharides group | 10 10 10 | 10mg/Kg body weight 60mg/Kg body weight | 1.15±0.22 0.87±0.20 0.93±0.10 | *0.0068 **0.0078 |
* simvastatin group and matched group are relatively: P＜0.05, * * astragalus polysaccharides and matched group compare: P＜0.05.
Test example three. the animal experiment of astragalus polysaccharides treatment hyperlipidemia
The therapeutic hyperlipidemia model:
The mensuration of normal blood value: get 60 of rats, body weight 170 ± 20g, male, be divided into 5 groups at random by body weight, every group 12, the rat normal feedstuff of feeding was observed 7 days under experimental situation, got tail blood, measure serum total cholesterol (TC), triglyceride (TG), HDL-C (HDL-C) level.Measurement result sees Table 11,12,13.Each is organized data and shows that every index is all within normal range.
The formation of hyperlipidemia model:Begin each treated animal from formal experiment and use high lipid food instead and fed 8 days, get tail blood, measure TC, TG,, the HDL-C level, measurement result sees Table 14,15,16, each is organized data and shows that every index meansigma methods all is higher than normal value.CHO normal value and hyperlipidemia model value relatively see Table 17, each organizes hyperlipidemia model value and normal value P value relatively all less than 0.05, so the judgement hyperlipemia model prepares successfully.
Grouping and dosage are calculated:According to the CHO level, divide 5 groups (seeing Table 18) at random again, 11 every group (Mus of 5 blood fat model differences is discarded).1 group is astragalus polysaccharides low dosage (40mg/kg) group; 2 groups is dosage in the astragalus polysaccharides (60mg/kg) group, and 3 groups is astragalus polysaccharides high dose (80mg/kg) group; 4 groups is the high lipid food matched group; 5 groups of positive matched groups.Irritate the stomach time: every morning 8:40.Grouping situation and respectively organize dosage and see Table 19.
Measure and observational technique:Each organized gastric infusion 14 days, and fasting be can't help water 16 hours in the time of the 15th day, and the tail vein is got blood, adopted enzymic colorimetric to measure serum total cholesterol value, triglyceride value and high density lipoprotein on full automatic biochemical apparatus.The gained data are carried out statistical procedures, represent with mean ± standard deviation, the significance of difference is judged with the T check.Calculated dosage every 5 days by the Mus body weight.
The result:
CHO result shows (seeing Table 20):
Low dosage astragalus polysaccharides group, middle dosage astragalus polysaccharides group and matched group compare: there is the utmost point significant difference P＜0.01; Simvastatin group and matched group compare: P＜0.05, there were significant differences.Above data show, three groups all have and significantly fall the T-CHOL effect, and there were significant differences.Simvastatin group and matched group relatively P value compare the P value greater than low, middle group of astragalus polysaccharides and matched group, illustrate that the T-CHOL effect of falling of astragalus polysaccharides is also better than positive control drug (simvastatin).
TG result shows (seeing Table 21):
Though the P value is all greater than 0.05, there was no significant difference.But each group of administration has reduced the TG level more in various degree with matched group.The P value of each administration group of astragalus polysaccharides shows that all less than the P value of positive control reduction TG level and positive control drug (simvastatin) are suitable.
HDL-C result shows (seeing Table 22):
Astragalus polysaccharides low dosage, high dose group and blank group relatively P value have significant difference all less than 0.05; Though dosage group and positive controls and the comparison of blank group all raise in various degree but do not have significance in the astragalus polysaccharides.The rising of HDL-C promotes lipid metabolism, so the lipid-reducing function of astragalus polysaccharides is than eager to excel in whatever one does many of positive control.
Table 11: the T-CHOL measurement result unit of normal rat: (mmol/L)
| 1 group | 2 groups | 3 groups | 4 groups | 5 groups | |
| 1 2 3 4 5 6 7 | 1.90 1.92 1.72 1.84 1.65 1.85 1.89 | 2.25 2.10 1.76 2.22 2.14 2.18 2.19 | 1.77 1.77 1.98 1.87 1.65 1.70 1.65 | 1.87 1.62 1.83 1.64 1.78 1.56 1.87 | 1.87 1.80 2.13 1.70 1.52 1.50 1.94 |
| 8 9 10 11 12 | 1.77 1.63 1.75 2.12 1.49 | 1.80 1.74 1.43 1.83 1.95 | 1.86 2.08 1.82 1.63 1.26 | 2.08 1.74 2.13 1.61 1.89 | 1.61 1.61 1.82 2.37 1.98 |
| Average value standard deviation | 1.79 0.16 | 1.97 0.26 | 1.75 0.21 | 1.80 0.18 | 1.82 0.26 |
Table 12: the triglyceride determination of normal rat is unit as a result: (mmol/L)
| 1 group | 2 groups | 3 groups | 4 groups | 5 groups | |
| 1 2 3 4 5 6 7 8 9 10 11 12 | 1.53 2.10 0.88 1.04 1.42 1.21 0.86 1.14 0.58 1.04 1.03 0.85 | 1.32 1.35 1.02 1.01 1.05 1.44 1.03 1.02 1.03 0.87 1.49 1.69 | 1.28 1.10 1.00 1.28 1.05 0.79 0.90 0.78 1.10 1.23 1.01 1.01 | 1.04 0.87 1.83 1.64 1.07 0.88 1.09 1.04 0.96 1.07 0.89 1.58 | 0.90 1.16 1.44 0.85 0.76 0.98 1.13 1.15 1.23 1.27 1.70 1.40 |
| The meansigma methods standard deviation | 1.14 0.40 | 1.19 0.25 | 1.04 0.17 | 1.03 0.19 | 1.16 0.27 |
Table 13: the high-density LP determination of normal rat is unit as a result: (mmol/L)
| 1 group | 2 groups | 3 groups | 4 groups | 5 groups | |
| 1 2 3 4 5 6 7 | 1.38 1.23 1.14 1.23 1.03 1.32 1.23 | 1.45 1.35 1.16 1.36 1.52 1.38 1.40 | 1.34 1.30 0.84 1.26 1.21 1.14 1.16 | 1.33 1.19 1.43 1.10 1.23 1.07 1.19 | 1.42 1.30 1.26 1.25 0.97 1.14 1.34 |
| 8 9 10 11 12 | 1.18 1.33 1.30 1.52 1.02 | 1.27 1.25 0.98 1.25 1.42 | 1.63 1.28 1.25 1.19 0.97 | 1.47 1.33 1.45 1.15 1.28 | 1.17 1.13 1.20 1.53 1.24 |
| The meansigma methods standard deviation | 1.24 0.14 | 1.32 0.15 | 1.21 0.19 | 1.27 0.14 | 1.25 0.15 |
Table 14: the T-CHOL measurement result unit of hyperlipidemia model rat: (mmol/L)
| 1 group | 2 groups | 3 groups | 4 groups | 5 groups | |
| 1 2 3 4 5 6 7 8 9 10 11 12 | 3.59 4.94 4.36 3.05 4.13 4.02 3.20 4.06 2.68 3.31 2.55 3.04 | 2.87 2.31 1.71 2.15 2.88 2.48 2.43 1.95 1.98 1.85 2.10 2.15 | 1.82 1.63 2.09 2.95 2.11 3.06 2.06 2.06 2.13 2.62 2.16 1.84 | 2.80 1.72 1.97 2.29 1.90 2.01 3.41 3.76 1.74 2.74 2.27 2.29 | 2.19 1.80 3.12 1.75 2.28 2.46 2.00 2.19 2.66 3.09 2.67 2.38 |
| The meansigma methods standard deviation | 3.58 0.73 | 2.24 0.37 | 2.21 0.44 | 2.41 0.65 | 2.38 0.47 |
Table 15: the triglyceride determination of hyperlipidemia model rat is unit as a result: (mmol/L)
| 1 group | 2 groups | 3 groups | 4 groups | 5 groups | |
| 1 2 3 4 5 6 7 | 1.20 1.69 1.02 1.10 0.88 1.13 1.15 | 1.06 1.03 0.74 0.76 1.18 0.85 0.69 | 1.02 0.77 1.05 1.52 1.15 1.21 1.08 | 1.11 1.04 0.76 1.09 1.18 1.34 1.29 | 0.88 0.75 1.22 0.03 0.95 1.22 1.16 |
| 8 9 10 11 12 | 1.29 0.97 1.05 1.06 0.96 | 0.88 0.95 0.78 0.96 0.87 | 1.00 0.87 1.24 1.17 1.20 | 1.34 1.30 1.04 0.73 0.90 | 0.65 1.16 1.27 1.11 0.88 |
| The meansigma methods standard deviation | 1.13 0.21 | 0.90 0.15 | 1.11 0.19 | 1.09 0.21 | 0.95 0.37 |
Table 16: the high-density LP determination of hyperlipidemia model rat is unit as a result: (mmol/L)
| 1 group | 2 groups | 3 groups | 4 groups | 5 groups | |
| 1 2 3 4 5 6 7 8 9 10 11 12 | 0.48 0.43 0.54 0.92 0.41 0.51 0.63 0.41 0.62 0.48 0.71 0.66 | 0.85 1.01 1.15 0.92 0.95 1.50 1.11 1.08 1.18 0.89 1.26 0.98 | 0.92 0.88 1.12 0.76 0.38 0.61 1.00 0.99 0.89 1.05 0.99 0.85 | 1.07 1.08 1.05 0.84 1.02 0.78 0.81 0.68 0.72 1.00 1.23 1.27 | 1.10 0.95 0.54 0.08 0.78 0.81 0.89 1.03 0.90 1.01 0.91 0.91 |
| The meansigma methods standard deviation | 0.57 0.15 | 1.07 0.18 | 0.87 0.21 | 0.96 0.19 | 0.83 0.28 |
Table 17: the comparative unit of T-CHOL normal value and hyperlipidemia model value: (mmol/L)
| 1 group | 2 groups | 3 groups | 4 groups | 5 groups | ||||||
| Normally | Model | Normally | Model | Normally | Model | Normally | Model | Normally | Model | |
| Meansigma methods | 1.79 | 3.58 | 1.97 | 2.24 | 1.75 | 2.21 | 1.80 | 2.41 | 1.82 | 2.38 |
| Standard deviation | 0.16 | 0.73 | 0.26 | 0.37 | 0.21 | 0.44 | 0.18 | 0.65 | 0.26 | 0.47 |
| The P value | 3×10 -8 | 0.0488 | 0.0037 | 0.0055 | 0.0016 | |||||
Table 18: according to T-CHOL value random packet situation unit: (mmol/L)
| 1 group | 2 groups | 3 groups | 4 groups | 5 groups | |
| 1 2 3 4 5 6 7 8 9 10 11 | 1-1 3.59 1-6 4.02 5-3 3.12 5-10 3.09 1-9 2.68 4-4 2.29 3-8 2.06 3-7 2.06 3-11 2.16 4-5 1.90 4-12 2.29 | 1-2 4.94 1-12 3.04 5-12 2.67 2-2 2.31 2-7 2.43 4-8 3.76 2-8 1.98 3-9 2.13 2-10 1.85 3-1 1.82 4-11 1.76 | 1-3 4.36 1-4 3.05 3-4 2.95 3-10 2.62 1-11 2.55 4-7 3.41 5-1 2.19 3-3 2.09 4-3 1.91 5-5 1.75 4-2 1.72 | 1-5 4.13 1-7 3.20 3-6 3.06 2-1 2.87 2-6 2.48 5-7 2.46 4-1 2.80 2-12 2.15 2-9 1.95 3-12 1.84 4-10 2.27 | 1-8 4.06 1-10 3.31 5-11 3.09 2-5 2.88 5-6 2.28 4-9 2.74 5-9 2.19 3-5 2.11 2-11 2.10 5-8 2.00 4-6 2.01 |
| The meansigma methods standard deviation | 2.70 0.73 | 2.61 0.98 | 2.60 0.81 | 2.66 0.66 | 2.615 0.666 |
Annotate: 1-1 represents former first a group Mus.
Table 19: the grouping situation reaches respectively organizes dosage
| Group | 1 | 2 | 3 | 4 | 5 |
| Medicine dosage (mg/Kg) | Low dosage (the thick Radix Astragali) 40 | Middle dosage (the thick Radix Astragali) 60 | High dose (crude polysaccharides) 80 | Blank (water) 60 | Positive control (simvastatin) 10 |
Table 20: T-CHOL measurement result unit: (mmol/L)
| Low dose group | Middle dosage group | High dose group | The blank group | Positive controls | |
| 1 2 3 4 5 6 7 8 9 10 11 | 1.98 2.51 2.42 2.07 2.50 2.08 2.30 2.23 2.59 1.91 2.26 | 2.25 2.00 2.30 2.35 2.28 2.21 1.97 1.91 2.18 1.77 1.76 | 2.75 2.88 2.18 1.87 3.72 2.18 2.26 2.40 2.02 1.79 3.42 | 2.46 2.75 3.41 2.53 2.78 2.64 2.41 3.32 2.93 2.31 2.40 | 2.55 2.32 2.70 2.88 2.11 2.70 2.34 2.07 1.97 2.25 1.79 |
| Average value standard deviation P value | 2.26 0.24 0.0032 | 2.09 0.21 8.3×10 -5 | 2.55 0.59 0.4362 | 2.72 0.37 | 2.33 0.34 0.0189 |
Table 21: triglyceride determination is unit as a result: (mmol/L)
| Low dose group | Middle dosage group | High dose group | The blank group | Positive controls | |
| 1 2 3 4 5 6 7 8 9 10 11 | 1.50 3.28 1.32 1.25 3.14 0.99 1.22 2.76 0.79 1.27 2.51 | 1.12 1.38 2.86 0.80 1.94 1.12 1.38 1.28 2.72 0.85 1.12 | 3.10 1.59 1.20 3.45 0.97 1.32 3.00 0.96 1.35 2.54 1.21 | 1.29 3.14 1.09 1.60 3.26 1.13 1.62 4.01 1.01 1.50 3.42 | 1.24 1.36 3.71 1.38 1.73 3.82 1.01 1.45 3.01 1.37 1.52 |
| Average value standard deviation P value | 1.82 0.91 0.5321 | 1.51 0.70 0.1531 | 1.88 0.94 0.6289 | 2.10 1.12 | 1.96 1.03 0.7734 |
Table 22: high-density LP determination is unit as a result: (mmol/L)
| Low dose group | Middle dosage group | High dose group | The blank group | Positive controls | |
| 1 2 3 4 5 6 7 8 9 10 11 | 0.62 0.65 0.55 0.48 0.71 0.87 0.68 0.67 0.76 0.65 0.52 | 0.53 0.57 0.75 0.61 0.58 0.44 0.66 0.68 0.46 0.63 0.71 | 0.65 0.69 0.54 0.55 0.71 0.59 0.80 0.58 0.61 0.79 0.84 | 0.49 0.65 0.61 0.60 0.54 0.52 0.56 0.50 0.66 0.54 0.44 | 0.41 0.38 0.68 0.60 0.49 0.56 0.48 0.55 0.51 0.57 0.35 |
| Average value standard deviation P value | 0.65 0.11 0.025 | 0.60 0.10 0.215 | 0.67 0.11 0.008 | 0.56 0.07 | 0.60 0.26 0.608 |
Lipid metabolism and cardiovascular disease are closely related, and hyperlipemia then is that to cause that atherosclerotic one of the main reasons, particularly serum total cholesterol level increase be atherogenic dangerous index.The height of serum lipid concentrations removes organism metabolism, and particularly outside the hormonal system regulation and control, the influence of exogenous material also is a very important aspect.Result of the test shows, with the blood fat reducing good medicine simvastatin on different two models and various dose astragalus polysaccharides and the market now relatively, finds preventative model, and two groups of comparison blanks all have certain T-CHOL effect of falling.Simvastatin group and matched group relatively P value compare the P value greater than astragalus polysaccharides and matched group, show that the T-CHOL effect of falling of astragalus polysaccharides is also better than positive control drug (simvastatin).Two groups more all have the effect of certain triglyceride reducing with blank, and there were significant differences.Simvastatin group and matched group relatively P value compare the P value less than astragalus polysaccharides and matched group, show that the triglyceride reducing effect of astragalus polysaccharides is good not as positive control drug (simvastatin).The therapeutic model result shows, astragalus polysaccharides to fall serum total cholesterol level, triglyceride reducing level, high density lipoprotein increasing level all strong than simvastatin.Toxicity test confirms astragalus polysaccharides safety, nontoxic again, show astragalus polysaccharides in preparation blood lipid-lowering medicine and health product application and in the medicine of preparation prevention and treatment cardiovascular and cerebrovascular disease and the application in the health product, have effect unique.
Claims (4)
1, astragalus polysaccharides is in the medicine of preparation blood fat reducing or the application in the health product.
2, the described application of claim 1, wherein the medicine of blood fat reducing or health product are meant the medicine or the health product of cholesterol reducing.
3, the described application of claim 1, wherein the medicine of blood fat reducing or health product are meant the medicine or the health product of triglyceride reducing.
4, the described application of claim 1, wherein the medicine of blood fat reducing or health product are meant the medicine or the health product of high density lipoprotein increasing.
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