CN100467025C - Use of asiaticoside in preparation of medicines for diseases of cardio-cerebral blood vessels - Google Patents
Use of asiaticoside in preparation of medicines for diseases of cardio-cerebral blood vessels Download PDFInfo
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- CN100467025C CN100467025C CNB2004100464892A CN200410046489A CN100467025C CN 100467025 C CN100467025 C CN 100467025C CN B2004100464892 A CNB2004100464892 A CN B2004100464892A CN 200410046489 A CN200410046489 A CN 200410046489A CN 100467025 C CN100467025 C CN 100467025C
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Abstract
An application of the asiaticoside in preparing the medicines in the form of capsule, tablet, particle, or injection for preventing and treating the cardiovascular and cerebrovascular diseases, such as coronary heart disease, angina pectoris, myocardial infarction, etc. is disclosed.
Description
Technical field:
The present invention relates to the new medicine use of Herba Centellae total glycosides, specifically relate to Herba Centellae total glycosides, belong to medical technical field in the purposes that is used for preparing the medicine of preventing and treating the heart, cerebrovascular disease.
Background technology:
Herba Centellae Centella asiatica (L.) Urban is a Umbelliferae Centella plant, is distributed widely in various places on the south the Yangtze river basin.All herbal medicine.In China's Herba Centellae external and existing more than the 2000 year history of curing the disease for oral administration.It has clearing away heat-damp and promoting diuresis, the function of removing toxic substances and promoting subsidence of swelling.Be applicable to jaundice due to damp-heat, heatstroke diarrhoea, sand Stranguria stranguria with blood, carbuncle sore tumefacting virus, injury from falling down.
The chemical constituent of Herba Centellae is based on triterpenes, as pentacyclic triterpene type ester glycosides such as asiaticoside (asiaticoside), asiaticoside (madecassoside), ripple hot-die glycosides (brahmoside), Bo Remi glycosides (brahminoside), thankuniside (thankuni-side), isothankuniside (isothankuniside), centelloside.Also contain some triterpene acids in the Herba Centellae, as: asiatic acid (asiatic acid), Madecassic acid (madecassic acid), Bo Remi acid (brahmic acid), madasiatic acid (madasiatic acid), centicacid, centoic acid, cenellic acid, indocentic acid etc.In addition, also have a spot of polyacetylene alkene class, volatile oil, beta-sitosterol, vanillic acid etc. in the Herba Centellae.
From content and active two aspects, Herba Centellae total glycosides is considered to pharmacological component and as the significant composition of Herba Centellae quality, mainly comprise two triterpene saponin of asiaticoside and asiaticoside (Chinese Chinese medicine information magazine, 2002,9 (8): 81-84).Asiaticoside molecular formula: C
48H
78O
19, molecular weight is 958.Asiaticoside molecular formula: C
48H
78O
20, molecular weight is 974.
The existing main pharmacologically active of Herba Centellae total glycosides has:
(1) to the effect of skin histology: Asiaticoside can promote wound healing, stimulates the granulation growth, promotes the epidermis keratinization, is used for the treatment of skin ulcer, as using in disease such as intractable wound, tuberculosis of skin, leprosy and the cosmetics for skin.By suppressing the synthetic of fibroblast proliferation and collagen protein, suppress cicatrization simultaneously.
(2) antibiotic: the in-vitro antibacterial experiment shows that Herba Centellae all has inhibitory action to golden yellow staphylococcus, haemolysis type streptococcus, various dysentery bacterium, Bacillus typhi.
(3) antiulcer: be used for the treatment of gastric ulcer.
(4) to central action: stimulate the central nervous system, be used for the treatment of depression, improve memory and resisting fatigue.Asiaticoside has spasmolytic, calmness, stable effect to mice and rat, mainly is the influence to cholinergic system among the central nervous system and gamma aminobutyric acid (GABA).
(5) alleviate the symptom that varicosis causes, this may have the structure of improving the blood vessel wall connective tissue and strengthen the venous function relevant with asiaticoside, is used for vein insufficiency of function (venous insufficiency).
(6) other: Herba Centellae total glycosides also has antiinflammatory, antioxidation, antitumor, treatment cyclomastopathy, anti-hepatic fibrosis, pulmonary fibrosis and renal fibrosis isoreactivity and purposes.
But up to the present, do not see the report that Herba Centellae total glycosides is used to prevent and treat coronary heart disease such as angina pectoris, myocardial infarction and cerebrovascular such as cerebral thrombosis, cerebral embolism as yet.
Coronary heart disease be since the blood vessel-coronary artery of supply heart nutrient substance taken place atherosis due to.Atherosclerotic plaque coronarius can make the coronary artery tube chamber serious narrow even inaccessible, causes the blood flow of cardiac muscle to reduce, and the oxygen supply deficiency occurs uncomfortable in chestly, feels suffocated angina pectoris, myocardial infarction even sudden death etc.The average at home prevalence of coronary heart disease is about 6.49%, and prevalence increases with age, thereby coronary heart disease is the modal a kind of cardiovascular disease of old people.The cause of coronary heart disease trend becomes younger at present, has become the commonly encountered diseases of middle-aged and elderly people.The medicine of coronary heart disease has nitrate preparations, beta-blocker, calcium channel blocker, antiplatelet drug and thrombolytic agent etc. at present, also have some Chinese patent medicines such as FUFANG DANSHEN PIAN, TONGXINLUO JIAONANG, DIAOXINXUE KANG and Xinnao Shutong etc., certain curative effect is arranged.But in general, China's independent intellectual property right, determined curative effect and not have the control medicaments for coronary disease of obvious toxic-side effects few are arranged.
Along with aged tendency of population, the cerebrovascular sickness rate constantly increases, and becomes one of healthy most important disease of harm humans.Die from the cerebrovascular patient and account for 11.3% in 57 countries of World Health Organization's investigation, wherein 40 national cerebrovascular account for cause of the death front three.World's average attack rate is 150～2,000,000/(100,000 population/year), and prevalence is 500～6,000,000/(100,000 population/year), and the whole world is by 5,000,000,000 people mental arithmetic, nearly 2500～30,000,000 patients.Die from the cerebrovascular patient more than heart disease and cancer in China, occupy three big cause of the death first places.The sickness rate of China's markization is 120～1,800,000/(100,000 population/year), prevalence is 4,290,000/(100,000 population/year), nearly 500～6,000,000 patients, wherein ischemic cerebrovascular occupies the majority, and comprises cerebral thrombosis, cerebral embolism, lacunar infarction and transient ischemic attack.Cerebral thrombosis, cerebral embolism have the characteristics of high incidence, high disability rate and high relapse rate, cause a large amount of group of handicapped, have brought heavy society and financial burden.The medicine method comprises expansion blood vessel, anticoagulant, antiplatelet aggregation and thromboembolism treatment.But the therapeutic effect of ischemic encephalopathy is also undesirable, still presses for the new medicine of research.
Summary of the invention:
The object of the present invention is to provide a kind of Herba Centellae total glycosides in the purposes that is used for preparing the medicine of preventing and treating the heart, cerebrovascular disease.Another purpose of the present invention also is to provide asiaticoside and asiaticoside in the purposes that is used for preparing the medicine of preventing and treating the heart, cerebrovascular disease.
Herba Centellae total glycosides of the present invention, main active ingredient is asiaticoside and asiaticoside.In rat heart muscle infarction model, therefore asiaticoside and asiaticoside active close need not further with asiaticoside and asiaticoside separately, need not also that the ratio between the two class glycosides can obtain satisfied curative effect in the further clear and definite total glycosides.Asiaticoside that is adopted among the embodiment and asiaticoside can adopt the already known processes preparation, also can adopt commercial commodity, and as asiaticoside and asiaticoside that Guangxi Chang Zhou natural product development corporation, Ltd. produces, its purity all reaches more than 95%.
The present invention extracts the processing step of Herba Centellae total glycosides from Herba Centellae as follows:
1, Herba Centellae is pulverized the back and use 75% alcohol reflux, 2 hours totally 3 times;
2, reclaim ethanol and get extractum;
3, extractum adds deionized water dissolving;
4, above-mentioned water-soluble liquid is decoloured by decolorizing resin, collect effluent, the reuse alcoholic solution is collected ethanol elution after by this decolorizing resin, merges above-mentioned effluent and ethanol elution;
5, the liquid of above-mentioned merging is evaporated to dried, thick thing;
6, with the above-mentioned thick thing of dissolve with methanol, ratio is thick thing (kg): the volume of methanol (ml)=1:100～500 gets Herba Centellae total glycosides solution;
7, with above-mentioned Herba Centellae total glycosides solution ethyl acetate crystallization, ratio is the volume (ml) of Herba Centellae total glycosides solution: the volume of ethyl acetate (ml)=1:1～100.Be evaporated to according to a conventional method dried, the white powder Herba Centellae total glycosides.Detect institute with the standard substance of asiaticoside and asiaticoside and HPLC method and carry the content of avenging asiaticoside and asiaticoside in the careless total glycosides.The Herba Centellae total glycosides of gained, wherein the content of asiaticoside and asiaticoside surpasses more than 40%, and possible is to surpass 60%, is preferably to surpass 80%, can satisfy the requirement of preparation control medicaments for coronary disease.
The applicant is in the process of screening treatment cardiovascular disease medicine, find that unexpectedly Herba Centellae total glycosides, asiaticoside and asiaticoside have significant anti-myocardial infarction activity, to being used to prevent and treat coronary heart disease, angina pectoris, myocardial infarction and painstaking effort brain pipe diseases such as cerebral thrombosis, cerebral embolism specially good effect is arranged, therefore the Herba Centellae total glycosides that contains asiaticoside and asiaticoside can be used to prepare the medicine of the control heart, cerebrovascular.It is with Herba Centellae total glycosides and medically acceptable excipient or the carrier preparation process according to routine, part by weight with 5-95:95-5, perhaps the part by weight of 1-9:9-1 make be suitable for the outer administration of gastrointestinal tract administration or gastrointestinal tract various dosage forms to patient's administration, as add pharmaceutical adjuvants such as conventional excipient, flavoring agent, antiseptic, lubricant, wetting agent, binding agent, solvent, thickening agent, solubilizing agent, make any dosage form that is suitable for clinical use, as: tablet, capsule, granule, drop pill, injection etc.
Because the present invention discloses Herba Centellae total glycosides first at the control heart, cerebrovascular pharmacologic action; therefore; Herba Centellae total glycosides cooperated separately or with other active constituent or adjuvant make medicament,, all belong to protection scope of the present invention so long as this medicament is used for the treatment of the heart, cerebrovascular disease.Herba Centellae total glycosides of the present invention all has the control heart, cerebrovascular effect when making any dosage form.
Results of pharmacodynamic test is as follows:
(1) utilizes isolated rat heart anoxia/reperfusion injury model, give Herba Centellae total glycosides 5mg/kg, 10mg/kg, Asiaticoside or each 5mg/kg of madecassoside, coronary flow is obviously increased, heart rate remains unchanged or slows down, the heartbeat rule, infarct size is obviously dwindled, and drops to 10.9% of Herba Centellae total glycosides 10mg/kg group from 33.7% of matched group, and effect is very remarkable.
(2) utilize ligation rat arteria coronaria to cause the acute myocardial infarction pathological model, observe the myocardium heart protective effect of asiaticoside and asiaticoside.Found that, 1h gavages Herba Centellae total glycosides 20mg/kg, 40mg/kg Asiaticoside or each 20mg/kg of madecassoside, 20mg/kg before the ligation, heart rate all slows down to some extent before making behind the coronary ligation rat than ligation, the rat electrocardiogram descends as S-T section, T ripple, creatine kinase in the rat blood serum (CK), lactic acid dehydrogenase (LDH) value all reduce than matched group, and myocardial infarction area is had the effect of significantly dwindling.Myocardial infarction area drops to 13.6% of Herba Centellae total glycosides 40mg/kg group, effect highly significant from 36.5% of matched group.
(3) utilize ligation dog M-LAD to cause dog myocardial infarction model, observe the myocardium protecting action of asiaticoside and asiaticoside.Found that Herba Centellae total glycosides can obviously reduce the myocardial infarction district weight that the ligation arteria coronaria causes, and relatively descends 49.2% with matched group, make the biochemical metabolism index LDH and the active obviously decline of CK of reflecting myocardium damage range simultaneously.
(4) utilize rat acute focal cerebral ischemia model to observe the curative effect of Herba Centellae total glycosides.There is the small pieces quantitative filter paper of 50% liquor ferri trichloridi (1mol/L hydrochloric acid) to spread on preparation cerebral thrombosis model on the intraluminal middle cerebral artery occlusion in rats suction.Successive administration is 3 days before the modeling, and laboratory animal is divided into: normal control group, model control group, Herba Centellae total glycosides 20mg/kg, Herba Centellae total glycosides 40mg/kg, asiaticoside 20mg/kg group, asiaticoside 20mg/kg group.Found that Herba Centellae total glycosides, asiaticoside and asiaticoside all can obviously dwindle brain infarction area, can obviously fall the brain water content that the middle cerebral artery thromboembolism causes.
In the present invention, if not refer in particular to, all amounts, part and percentage ratio are unit of weight, and all equipment and raw material etc. all can be buied from market or the industry is commonly used.
Below in conjunction with embodiment in detail the present invention is described in detail, can not limits the scope of the invention but embodiment only is used for explanation.
The specific embodiment
The preparation of embodiment 1 Herba Centellae total glycosides
Get 1 kilogram of fresh dried Herba Centellae and pulverize, the 75% ethanol elder generation soaked overnight with 3 liters refluxed 2 hours again, carried out altogether 3 times, reclaimed ethanol, and conventional concentrating under reduced pressure gets extractum.Extractum is added 3 liters of deionized water dissolving, again water-soluble liquid is added to decolorizing resin, collect effluent, reuse 60% alcoholic solution is collected ethanol elution after by this decolorizing resin, merges above-mentioned effluent and ethanol elution.The liquid of above-mentioned merging is evaporated to dried, thick thing.With 500 milliliters of above-mentioned thick things of analytical pure dissolve with methanol, get Herba Centellae total glycosides solution.The crystallization of 4 liters of analytical pure ethyl acetate of reuse in 40 ℃ of vacuum dryings, obtains 21.1 gram white powder solids.
The preparation of embodiment 2 capsules
Herba Centellae total glycosides raw material 500 grams, medical starch 1000 grams stir, the capsule of packing into No. 0, every 0.3 gram, each oral 2, every day three times.
Embodiment 3 preparation tablets
Herba Centellae total glycosides raw material 500 grams, medical starch 500 grams stir, and use an amount of alcohol granulation, through granulate, tabletting, every 0.2 gram, oral, each 2, every day three times.
The preparation of embodiment 4 granules
Herba Centellae total glycosides raw material 200 gram, medical starch 4000 grams, sucrose 800 grams, mix homogeneously use an amount of alcohol granulation, drying, granulate, packing promptly, every bag 5 restrains, each 1 bag, every day three times.
The preparation of embodiment 5 drop pill
Take by weighing the poly-ethanol 4000 of 300 grams and be substrate, in water-bath, dissolve, add Herba Centellae total glycosides raw material 100 grams, stir, in the impouring insulating tube, with thermostat insulation, the poly-ethanol liquid that contains Herba Centellae total glycosides is splashed in the liquid paraffin of pre-cooling (4-10 ℃), after dripping off under 80-90 ℃ of condition, to blot paraffin oil on the pill impouring filter paper, add a small amount of Pulvis Talci again, mixing gets 1000 of drop pills of centella total glycoside.Oral, 1 time 2,3 times on the 1st.
The preparation of embodiment 6 injections
Herba Centellae total glycosides raw material 30 grams, propylene glycol 40ml, Polyethylene Glycol-400100ml mixes, and heating in water bath 30min adds the injection water to 600ml, handles 20min in the ultrasound wave, heats in water-bath again, regulates pH value 7.0-7.2.Filter, embedding, sterilization is promptly.Every 2ml, intramuscular injection, 1 2ml, every day 3 times, or and normal saline, 5% Glucose Liquid 500ml, behind the mixing, intravenous drip, every day 1 time, each 3.
Embodiment 7 Herba Centellae total glycosidess are to the influence of isolated rat heart anoxia/reperfusion injury
Wistar cleans rat, and is male, body weight 200-240g.Herba Centellae total glycosides prepares voluntarily, and reference substance asiaticoside (purity is greater than 95%) and asiaticoside (purity is greater than 95%) are available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.Herba Centellae total glycosides and hydroxyl amass careless glycosides physiological saline solution, the asiaticoside anhydrous alcohol solution, and the dilution of reuse normal saline, the ethanol final concentration is 0.1% (V/V).Red tetrazolium (TTC) is produced by Shanghai reagent three factories, potassium phosphate buffer (pH7.8) autogamy, heparin sodium injection, the Shanghai first biochemical Pharma Inc., lactic acid dehydrogenase (LDH) test kit, creatine phosphokinase (CK) test kit are produced by Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd..The Langendorff perfusion device, Japanese photoelectricity electrocardiograph, SABA-18 automatic clinical chemistry analyzer.
Get the rat that body weight is 200-240g, lumbar injection 500U/kg anticoagulant heparin, inject amobarbital sodium (30mg/kg) anesthesia behind the 15min, opening the thoracic cavity rapidly, expose heart, break pericardium, mention gently after isolating heart, cut with the elbow tissue in aortic root 5-7mm place and cut off superior and inferior vena cava rapidly, pulmonary artery, aorta and heart surrounding tissue extract heart, place the K-H liquid of pre-cooling (4 ℃), push heart gently with finger, make residue blood discharge in the heart, artery-clogging is fixed in aorta on the sleeve pipe of perfusion device with silk thread in case the hemostasis-coagulation piece forms.Perfusion drives in the wrong direction with 37.5 ℃ perfusate constant voltages (pressure altitude is the 75cm water column).Krebs-Henseleit (K-H) balanced natritive liquid, constituent is (mmol/L): NaCl 118, KCl 4.63, MgCl
21.2, CaCl
24.8, NaHCO
325, KH
2PO
41.17 glucose 11.0 feeds 95%O with nutritional solution earlier before the experiment
2And 5%CO
2Gaseous mixture 10min carry out fully saturatedly, throughput is 1.0L/min, pH7.4.In experimentation, heart is placed in the glass cell to remain in 38 ± 1 ℃ the external environment.Cut off heart adhering tissue on every side, cut off an osculum in pulmonary artery initial part and circular cone position, right ventricle, help the discharge of arteria coronaria backflow, measuring effluent with measuring graduate is coronary flow.Regularly collect the arteria coronaria effluent, record 1min coronary flow (CF) is with the lactic acid dehydrogenase (LDH) and creatine phosphokinase (CK) content of full automatic biochemical apparatus mensuration effluent.Insert platinum electrode in left ventricle portion and right atrium portion respectively, trace electrocardiogram II and lead, be used to observe heart rate (HR), S-T section, T ripple, R ripple, the Q-T variation of interval.The retrograde perfusion 10min of heart is an equilibration time, utilize constant flow pump that 5ml normal saline or medicinal liquid (1mg or the 2mg dose) speed with 0.5ml/min is poured in the heart with perfusate, wear No. 000 silk thread in the anterior descending coronary root behind the administration 10min, together with the ligation of 1mm diameter sticking plaster, take out sticking plaster behind the 30min, make the logical again 60min of anoxia cardiac muscle of anterior descending coronary domination.After experiment finishes, heart taken off be cut into thick 5 of 0.1cm, myocardium sheet is placed in 1% the TTC phosphate buffer solution, pH7.8 is incubated 15min 37 ℃ of temperature, and normal myocardium dyes and is redness, the cardiac muscle of infarcted region is not painted or shallow painted, after the dyeing myocardium sheet is put into 10% formalin and fixes.Take by weighing whole-heartedly with electronic balance heavy, again clip not colour attaching area (infarcted region cardiac muscle) weigh the calculating myocardium infarct size.Heavy (mg) * 100% of myocardial infarction area (%)=infraction heavy (mg)/whole-heartedly.
Found that Herba Centellae total glycosides can make coronary flow increase, wherein increase obviously,, show the myocardial preservation activity of Herba Centellae total glycosides all than matched group height (table 1) with Herba Centellae total glycosides 10mg/kg dosage group and asiaticoside, asiaticoside.
The influence that coronary flow changed due to table 1 Herba Centellae total glycosides poured into the isolated rat heart anoxia again
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01.L: ligation; R: irritate again
After giving Herba Centellae total glycosides, asiaticoside and asiaticoside, each is organized heart rate and all slightly slows down to some extent.Ligation and irritate back matched group heart heart rate slack-off (table 2) again.Herba Centellae total glycosides and asiaticoside, asiaticoside can make heart rate accelerate or keep normal.
The influence of changes in heart rate due to table 2 Herba Centellae total glycosides pours into the isolated rat heart anoxia again
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01.L: ligation; R: irritate again
Herba Centellae total glycosides, asiaticoside and asiaticoside all can make myocardial infarction area dwindle (table 3), and the Herba Centellae total glycosides high dose group is similar with asiaticoside group effect to the asiaticoside group.
The influence of myocardial infarction area due to table 3 Herba Centellae total glycosides pours into the isolated rat heart anoxia again
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01,
* *P＜0.001.
Embodiment 8 Herba Centellae total glycosidess cause the influence of acute myocardial infarction to the ligation rat coronary artery
Wistar cleans rat, and is male, body weight 200～240g.Reference substance asiaticoside (purity is greater than 95%) and asiaticoside (purity is greater than 95%) are available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.Red tetrazolium (TTC) is produced by Shanghai reagent three factories; potassium phosphate buffer (pH7.8) autogamy; pentobarbital sodium, Shanghai chemical reagents corporation, lactic acid dehydrogenase (LDH) test kit, creatine phosphokinase (CK) test kit are produced by Zhongsheng Beikong Biological Science ﹠ Technology Co., Ltd..Experimental apparatus: HXQ-1 artificial respirator, Japanese photoelectricity electrocardiograph, SABA-18 automatic clinical chemistry analyzer, IEC centrifuge.
Get 200～240g rat, grouping: 1. model control group; 2. Herba Centellae total glycosides 20mg/kg organizes, 3. Herba Centellae total glycosides 40mg/kg organizes.2. asiaticoside 20mg/kg organizes, 3. asiaticoside 20mg/kg organizes.Gavage administration with 1% sodium carboxymethyl cellulose mixing, after 1 hour, pentobarbital sodium (30mg/kg) abdominal cavity light anaesthesia, back of the body position is fixing.Be connected to artificial respirator with more than half rubber bulb (size is just in time entangled the rat incidence), practice artificial respiration.Chest unhairing, sterilization, along the about 2cm of left mid-clavicular line longitudinal incision skin, separate the flesh layer in the 4th or the 5th intercostal passivity, open the thoracic cavity, cut off pericardium, gently press the right side thorax, extrude heart.Behind ligation anterior descending branch in Coronary vein place between arterial cone and the left auricle, heart is put back to the thoracic cavity.Close the thoracic cavity rapidly, stop the artificial respiration, push chest gently, make heartbeat recover normal, place in the cage for animal and observe with forefinger and thumb.Before using electrocardiograph to write down ligation respectively, 2h, 4h, 6h electrocardiogram after the ligation are used to observe the S-T section and change.Ligation 6 hours after pentobarbital sodium (30mg/kg) abdominal cavity light anaesthesia, is opened the abdominal cavity, extract 5ml venous blood from postcava, use centrifuge, centrifugal 20 minutes with 3000 rev/mins, get serum, utilize full automatic biochemical apparatus to measure the content of serum lactate dehydrogenase (SLD) (LDH) and creatine phosphokinase (CK).After experiment finishes, the rat heart taking-up is placed in the cardiac muscle section mould, be cut into thick 5 of 0.1cm and put into 1% TTC phosphate buffer solution, pH7.8, incubate 15min 37 ℃ of temperature, normal myocardium dyes and is redness, and the cardiac muscle of infarcted region is not painted or shallow painted, after the dyeing myocardium sheet is put into 10% formalin and fix, take the myocardial infarction shade.Take by weighing whole-heartedly heavy, Zuo Xinchong with electronic balance, again clip not colour attaching area (myocardial infarction district) weigh the calculating myocardium infarct size.
Heavy (mg)/whole-heartedly flesh of muscle infarction area (%)=infraction weighs (mg) * 100% whole-heartedly
Left side myocardial infarction area (%)=infraction heavy (mg)/heavy (mg) * 100% of left side cardiac muscle
Found that Herba Centellae total glycosides, asiaticoside and asiaticoside all have the decline effect to heart ligation arteria coronaria rat S-T section, wherein at ligation 2h and 4h comparatively obviously (table 4).
The influence that table 4 Herba Centellae total glycosides changes S-T section due to the rat heart ligation arteria coronaria
Annotate: with the matched group ratio,
*P＜0.05,
*P＜0.01,
* *P＜0.001.
CK, LDH value are all than matched group low (table 5) in Herba Centellae total glycosides high dose group, asiaticoside group and the asiaticoside group rat blood serum.
The influence that table 5 Herba Centellae total glycosides changes CK, LDH value due to the rat heart ligation arteria coronaria
Annotate: with the matched group ratio,
*P＜0.05.
Herba Centellae total glycosides, asiaticoside and asiaticoside have the effect significantly dwindled (table 6) to heart ligation arteria coronaria rat model myocardial infarction area.
Table 6 Herba Centellae total glycosides is to the influence of myocardial infarction area due to the rat heart ligation arteria coronaria
Annotate: compare with matched group,
*P＜0.05,
*P＜0.01,
Embodiment 9 Herba Centellae total glycosidess are to the influence of dog acute myocardial infarction
Make and select 36 of healthy adult domesticated dogs, the male and female dual-purpose, overnight fasting is divided into 6 groups at random, 6 every group.Grouping and dosage see Table.Gavage administration after 3 hours with domesticated dog with urethane anesthesia and be fixed in operating-table, circulation of qi promoting cannula art connects artificial respirator, the 4th intercostal is opened breast and is exposed heart in the left side then, cuts off pericardium and ligation M-LAD.After 6 hours, get the activity of hematometry LDH and CK; Take out and weigh whole-heartedly and crosscut becomes the plurality of thin piece, put 1% triphenyltetrazolium chloride (TTC) solution into and make specimen dyeing 10min substantially, normal myocardium is dyed is peony, and infarcted region is not painted.Carefully cut non-staining cardiac muscle and weigh, the calculating myocardium infarction partly accounts for the percentage ratio of weight whole-heartedly, sees Table 1.The result shows that Herba Centellae total glycosides can obviously dwindle the myocardial infarct size that the ligation arteria coronaria causes, and makes the biochemical metabolism index LDH and active obviously descend (table 7) of CK of reflecting myocardium damage range simultaneously.
Table 7 Herba Centellae total glycosides is to the influence of dog myocardial infarction due to the coronary ligation
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01
Embodiment 10 Herba Centellae total glycosidess are to the influence of rat acute focal cerebral ischemia
The Wistar rat, male, body weight 210 ± 20 grams.Secondary.Being divided into 2 batches carries out.Reagent chloro triphenyltetrazolium chloride (TTC) Beijing Chemical Plant produces.Every batch of animal is divided into 8 groups at random by body weight: normal control group, model control group, Herba Centellae total glycosides 20mg/kg, Herba Centellae total glycosides 40mg/kg, asiaticoside 20mg/kg group, asiaticoside 20mg/kg group.Irritate stomach by body weight and give each medicinal liquid 0.5ml/100g body weight, normal control group and model control group give the equal-volume normal saline, successive administration 3 days.1h behind the 2nd day medicine, pentobarbital sodium (35mg/kg) intraperitoneal injection of anesthesia.Press literature method, expose rat right side middle cerebral artery, have the small pieces quantitative filter paper of 50% liquor ferri trichloridi (1mol/L hydrochloric acid) to spread on the middle cerebral artery suction,, sew up wound with taking off filter paper after the anatomic microscope observation thrombosis.Matched group covers the ferric chloride filter paper the same model group of all the other operating procedures except that not applying.23h gastric infusion 1 time again after the modeling.24h after modeling, broken end is got brain.The mensuration of cerebral infarct size: rat broken end back is taken out full brain rapidly, removes olfactory bulb, cerebellum and low brain stem, and remainder is crown under 4 ℃ to be cut into 5.(every 5ml dye liquor contains 4%TTC1.5ml, 1mol/L K rapidly the brain sheet to be placed the TTC dye liquor
2HPO
40.1ml), 37 ℃ of lucifuge temperature are incubated 30min, take out to be placed in 10% formalin to keep in Dark Place.The non-ischemic region in dyed back is a rose, and infarct is a white.The white tissue is weighed careful the separation, account for the percentage ratio of total brain weight as cerebral infarct size with blocking tissue's weight.The mensuration of brain water content: rat broken end back is taken out full brain rapidly, gets right half brain ball, claims weight in wet base, and 110 ℃ of oven dry 24h claim dry weight, calculate brain water content.
Found that Herba Centellae total glycosides, asiaticoside and asiaticoside all can obviously dwindle brain infarction area, can obviously reduce the water content of middle cerebral artery thromboembolism rat brain.
Table 8 Herba Centellae total glycosides is to the influence of rat acute focal cerebral ischemia
Annotate: compare #P＜0.05 with the normal control group; Compare with model control group,
*P＜0.05,
*P＜0.01
Claims (8)
1, Herba Centellae total glycosides, asiaticoside or asiaticoside are used to prepare the purposes of the medicine of preventing and treating the heart, cerebrovascular disease.
2, according to the purposes of the described Herba Centellae total glycosides of claim 1, asiaticoside or asiaticoside, it is characterized in that being used to prepare the purposes of the medicine of preventing and treating cardiovascular disease, described cardiovascular disease comprises coronary heart disease, angina pectoris, myocardial infarction.
3, according to the purposes of the described Herba Centellae total glycosides of claim 1, asiaticoside or asiaticoside, it is characterized in that being used to prepare the purposes of the medicine of preventing and treating cerebrovascular disease, described cerebrovascular disease comprises cerebral thrombosis, cerebral embolism.
4,, it is characterized in that asiaticoside and asiaticoside content sum are more than or equal to 40% in the Herba Centellae total glycosides according to the purposes of the described Herba Centellae total glycosides of one of claim 1-3.
5, according to the purposes of the described Herba Centellae total glycosides of one of claim 1-3, Herba Centellae total glycosides wherein is to adopt to be prepared as follows method and to make from Herba Centellae:
(1) Herba Centellae is pulverized the back and use 75% alcohol reflux, 2 hours totally 3 times;
(2) reclaim ethanol and get extractum;
(3) extractum adds deionized water dissolving;
(4) above-mentioned water-soluble liquid is decoloured by decolorizing resin, collect effluent, the reuse alcoholic solution is collected ethanol elution after by this decolorizing resin, merges above-mentioned effluent and ethanol elution;
(5) liquid of above-mentioned merging is evaporated to dried, thick thing;
(6) with the above-mentioned thick thing of dissolve with methanol, ratio is thick thing (kg): the volume of methanol (ml)=1:100～500 gets Herba Centellae total glycosides solution;
With above-mentioned Herba Centellae total glycosides solution ethyl acetate crystallization, ratio is the volume (ml) of Herba Centellae total glycosides solution: the volume of ethyl acetate (ml)=1:1～100, be evaporated to according to a conventional method dried, the white powder Herba Centellae total glycosides.
6, according to the purposes of the described Herba Centellae total glycosides of one of claim 1-3, it is characterized in that Herba Centellae total glycosides and medically acceptable excipient or carrier are mixed, make pharmaceutical composition, its form can be tablet, capsule, granule, drop pill, injection.
7, the purposes of Herba Centellae total glycosides according to claim 6 is characterized in that Herba Centellae total glycosides and medically acceptable excipient or carrier mix with the part by weight of 5-95:95-5.
8, the purposes of Herba Centellae total glycosides according to claim 6 is characterized in that Herba Centellae total glycosides and medically acceptable excipient or carrier mix with the part by weight of 1-9:9-1.
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| US9155744B2 (en) | 2005-10-27 | 2015-10-13 | Lead Billion Limited | Pharmaceutical composition and method for regenerating myofibers in the treatment of muscle injuries |
| ES2358306T3 (en) * | 2007-02-12 | 2011-05-09 | Indus Biotech Private Limited | A COMPOSITION FOR THE SELECTIVE INHIBITION OF THE REABSORTION OF SERETONIN AND THE CORRESPONDING PROCESSES. |
| CN101396384B (en) * | 2007-09-28 | 2012-11-21 | 天津天士力现代中药资源有限公司 | Asiatic centella extract and preparation methode thereof |
| BR112012031095B1 (en) * | 2010-06-10 | 2020-05-05 | Indus Biotech Private Ltd | method for preparing a highly pure asiaticoside composition from centella asiatica for a method for its use |
| CN102389437A (en) * | 2011-06-24 | 2012-03-28 | 中国人民解放军第二军医大学 | Application of Centella triterpenes in preparing products for improving cerebral apoplexy sequelae |
| CN103735689B (en) * | 2014-01-21 | 2016-01-20 | 吉林省中医药科学院 | A kind of natural drug composition is preparing the application in anoxia enduring medicine and health product |
| CN117838710A (en) * | 2022-09-30 | 2024-04-09 | 浙江普利药业有限公司 | Application of pentacyclic triterpene compound in preparation of medicine for preventing and/or treating sarcoidosis |
| CN115944567A (en) * | 2022-10-24 | 2023-04-11 | 广州好肌肤科技有限公司 | Centella asiatica extraction method with anti-inflammatory effect and application |
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Non-Patent Citations (2)
| Title |
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| Cardioprotective activity of HydrocotyleasiaticaL.inischemia-reperfusion induced myocardial infarctionin rats. R.R.Pragada,K.K.Veeravalli,K.P.R.Chowdary,K.V.Routhu.Journal of ETHNOPHARMACOLOGY,No.93. 2004 |
| Cardioprotective activity of HydrocotyleasiaticaL.inischemia-reperfusion induced myocardial infarctionin rats. R.R.Pragada,K.K.Veeravalli,K.P.R.Chowdary,K.V.Routhu.Journal of ETHNOPHARMACOLOGY,No.93. 2004 * |
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