CN101167784A - Medicinal composition for cardiovascular and cerebrovascular diseases - Google Patents
Medicinal composition for cardiovascular and cerebrovascular diseases Download PDFInfo
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Abstract
The invention belongs to the field of medicine technique and discloses a medicament composition of barren wort or extract and kudzu root or extract, process for preparation of the medicament composition, application in preparing medicament for curing cardio-cerebrovascular disease, and medicament which contains the medicament composition. According to the part by weight, components of raw material medicine for preparing the medicament composition are as follows: barrel wort 250-8000 parts, kudzu root 125-2000 parts, or barrel wort extract 5-240 parts and kudzu root extract 3.5-100 parts, which can be prepared into any acceptable clinical or pharmaceutical dosage forms, and the optimal selection is oral medicament or injecting medicament. Two medicaments in the medicament composition of the invention have synergistic interaction. Compared with the independent usage of barren wort or extract and kudzu root or extract, the therapeutic effect is greatly enhanced. Two medicaments simultaneously increase blood flow in the coronary atery and improve blood flow mechanics and cerebrovascular circulation and have the functions of anti-myocardial ischemia, and anti-platelet aggregation and the like.
Description
[technical field]
The present invention relates to pharmaceutical composition of Herba Epimedii or its extract and Radix Puerariae or its extract and preparation method thereof, the application in the medicine of preparation treatment cardiovascular and cerebrovascular disease and contain the preparation of this pharmaceutical composition, belong to medical technical field.
[background technology]
Cardiovascular and cerebrovascular disease comprises coronary heart disease, angina pectoris, myocardial infarction, blood stasis type pulmonary heart disease, ischemic encephalopathy, cerebral thrombosis, hypertension, hyperlipidemia etc.The main pathogenic factor of these diseases is that arteriosclerosis causes luminal stenosis, pipeline obstruction, thereby causes cerebral ischemia, causes that head is heavy, dizziness, headache, symptom such as uncomfortable in chest, and severe patient can cause the generation of apoplexy and myocardial infarction.Influence energy metabolism behind the cardiac-cerebral ischemia, multiple variations such as the accumulation of secondary lactic acid, calcium overload, radical damage.Cardiovascular and cerebrovascular disease all is the formidable enemy who threatens human health all the time, seizes more than 1,200 ten thousand people's life every year, near 1/4 of the total death of population.Along with China progresses into aged society, and change along with expanding economy and life style, dietary habit, the prevalence of cardiovascular and cerebrovascular disease and mortality rate rise just year by year, predict according to World Health Organization (WHO), to the year two thousand twenty, noninfectious will account for 79% of China's cause of death, and wherein cardiovascular and cerebrovascular disease will account for the first place.Therefore, how effectively to prevent and treat the great attention that cardiovascular and cerebrovascular disease also just causes people.At present, the diagnosis of cardiovascular and cerebrovascular disease and control are worldwide research focuses, also are the important contents of Chinese medical theory and clinical research.
Herba Epimedii is the dry aerial parts of Berberidaceae plant Herba Epimedii EPimedium brevicornum Maxin., arrow leaf Herba Epimedii EPimediumsagittatum Maxin., pubescence Herba Epimedii EPimedium Pubescens Maxin., Epimedium wushanense EPimediumwushanense T.S.Ying or Herba Epimedii EPimedium koreanum Nakai..Warm in nature, acrid in the mouth, sweet is returned liver, kidney channel.Herba Epimedii is used as medicine and starts from Shennong's Herbal, classifies middle product as; Compendium of Material Medica claims it that effect of " beneficial vital essence, hard muscles and bones, by the waist knee joint, heart tonifying power " is arranged.In recent years, for the resources of medicinal plant of comprehensive utilization Epimedium, carried out extensive studies.The modern pharmacology experimentation shows that Herba Epimedii can improve hemorheology, increases the cardiovascular and cerebrovascular vessel blood flow, promote the hemopoietic system function, regulate body's immunity, improve bone metabolism, delay the process of renal failure, strengthen the arrenotoky function, have effects such as defying age, antitumor.The modern chemistry composition Study shows that the main effective ingredient of Herba Epimedii is Herba Epimedii total flavones and epimedium brevicornum polysaccharide.
The main effective ingredient of Herba Epimedii extract is a Herba Epimedii total flavones, mainly contains icariin and icariside etc.Pharmacological research finds that Herba Epimedii total flavones is that Herba Epimedii promotes immunologic function, the effective ingredient of functions such as enhancing cardiovascular activity.Icariin has effects such as coronary blood flow increasing, cerebral blood flow increasing amount, can be used for coronary heart disease, climacteric hypertension, sensation of oppression over the chest with shortness of breath and rheumatism etc.
Radix Puerariae is the dry root of legume pueraria lobata Pueraria lobata (Willd.) Ohwi.Practise and claim Herba Gelsemii Elegantis.Property suffering, cold, sweet in the mouth is returned spleen, stomach warp.Be good at expelling pathogenic factors from muscles for reducing heat, promote the production of body fluid, rash, yang invigorating antidiarrheal.Be mainly used in fever caused by exogenous pathogens headache, stiff nape and back, thirsty, quench one's thirst, measles without adequate eruption, hematodiarrhoea is had loose bowels, the hypertension neck pain.
The main effective ingredient of Radix Puerariae extract is a Radix Puerariae total flavones, mainly contains puerarin, daidzein, daidzin, seven material lignin etc.The pharmacological action of Radix Puerariae has the cerebral circulation of improvement, arrhythmia, resist myocardial ischemia, reduce myocardial oxygen consumption and do not have obvious negative inotropic action, also have antithrombotic, improve effects such as high density lipoprotein, vasospasm and reduction platelet aggregation.The clinical diseases such as treatment retinal artery occlusion, coronary heart disease, angina pectoris, hypertension, cerebral arteriosclerosis, migraine, hyperlipidemia that are mainly used in.
Utilize the interaction of Herba Epimedii or Herba Epimedii extract and Radix Puerariae or Radix Puerariae extract at present, composition of prescription, the medicine of aspects such as preparation treatment cardiovascular and cerebrovascular disease does not appear in the newspapers as yet.
[summary of the invention]
In order to meet clinical needs, better treat cardiovascular and cerebrovascular disease etc., improve the people ' s health level, the invention provides pharmaceutical composition of Herba Epimedii or its extract and Radix Puerariae or its extract and preparation method thereof, preparing the preparation for the treatment of the application in the cardiovascular and cerebrovascular disease and containing this pharmaceutical composition.
The crude drug of making the contained composition and effectiveness of pharmaceutical composition of the present invention is Herba Epimedii, Radix Puerariae, pharmaceutical composition of the present invention have significantly resist myocardial ischemia, coronary blood flow increasing, antiplatelet aggregation, improve the blood flow mechanics, improve the cerebrovascular circulation, remove free radical, the fast shut-off free radical chain reactions, suppress lipid peroxidation, effects such as anti-hypoxia have produced beyond thought effect.
Prove, calculate to have remarkable synergistic function in 250～8000 parts of Herba Epimedii, 125～2000 parts of scopes of Radix Puerariae according to composition by weight through a large amount of screening experiment of inventor; Be preferably: 500～4000 parts of Herba Epimedii, 250～1000 parts of Radix Puerariaes; More preferably: 1000～2000 parts of Herba Epimedii, 500 parts of Radix Puerariaes.
Herba Epimedii in the aforementioned pharmaceutical compositions and Radix Puerariae can be with The suitable solvent respectively or mix through extracting processing and obtain its extract, total extract is made preparation with the pharmaceutic adjuvant hybrid process again, and the main effective ingredient of gained total extract is a flavone compound.Described solvent is meant solvent pharmaceutically commonly used, preferred water or alcohol, and extracting method can extract with pharmaceutically conventional method, as decocting method, percolation, reflux extraction, continuous extraction etc.
Herba Epimedii in the aforementioned pharmaceutical compositions can extract preparation by following selection process, but is not limited only to following technology:
Technology one: get epimedium herb, be ground into middle powder, add 12 times of amounts of 70% ethanol, soaked 12 hours, filter filtrate for later use; Medicinal residues add 70% ethanol heating extraction three times, each 1.5 hours, filter, merging filtrate, filtrate decompression is concentrated in right amount, on the D101 macroporous resin column handled well, use earlier the distilled water eluting, reuse 15% ethanol elution, use 70% ethanol elution at last, collect eluent, decompression recycling ethanol, vacuum drying, promptly.Herba Epimedii extract yield by this prepared is 2～3%, and the content of Herba Epimedii total flavones is not less than 50%, and content Determination of Icariin is not less than 4%.
Technology two: get epimedium herb, be ground into middle powder, add 12 times of amounts of 70% ethanol, soaked 12 hours, filter filtrate for later use; Medicinal residues add 70% ethanol heating extraction three times, each 1.5 hours, filter merging filtrate, filtrate decompression is concentrated in right amount, on the polyamide column handled well, use earlier distilled water eluting, reuse 15% ethanol elution, use 70% ethanol elution at last, collect eluent, decompression recycling ethanol, vacuum drying.Herba Epimedii extract yield by this prepared is 1～3%, and the content of Herba Epimedii total flavones is not less than 50%, and content Determination of Icariin is not less than 3%.
Technology three: get epimedium herb, be ground into middle powder, add 12 times of amounts of 70% ethanol, soaked 12 hours, filter filtrate for later use; Medicinal residues add 70% ethanol heating extraction three times, each 1.5 hours, filter merging filtrate, be evaporated to driedly, dissolve filtered while hot repeatedly three times with 5% sodium carbonate liquor heating, it is 2 that filtrate adds the hydrochloric acid adjust pH, puts coldly, separates out precipitation, filter, the precipitation vacuum drying is used n-butyl alcohol heating and refluxing extraction three times, each 20 minutes, filter merging filtrate, filtrate decompression reclaims n-butyl alcohol, vacuum drying, promptly.Herba Epimedii extract yield by this prepared is 1～3%, and the content of Herba Epimedii total flavones is not less than 50%, icariin content be not less than 3%.
Technology four: get epimedium herb, be ground into middle powder, add 12 times of amounts of 70% ethanol, soaked 12 hours, filter filtrate for later use; Medicinal residues add 70% ethanol heating extraction three times, each 1.5 hours, filter, merging filtrate, filtrate decompression are concentrated in right amount, use ethyl acetate extraction 4 times, combined ethyl acetate liquid, reclaim under reduced pressure ethyl acetate, vacuum drying, get residue n-butyl alcohol heating and refluxing extraction three times, each 20 minutes, merge extractive liquid,, reclaim under reduced pressure n-butyl alcohol, vacuum drying, promptly.Herba Epimedii extract yield by this prepared is 1～3%, and the content of Herba Epimedii total flavones is not less than 40%, and content Determination of Icariin is not less than 4%.
Radix Puerariae in the aforementioned pharmaceutical compositions can extract preparation by following selection process, but is not limited only to following technology:
Technology one: get the Radix Puerariae medical material, pulverize, add 70% alcohol heating reflux and extract twice, add 12 times of amounts of alcohol for the first time, extracted 2 hours, and added 10 times of amounts of alcohol for the second time, extracted 1 hour, merge extractive liquid, filters, and filtrate is concentrated into does not have the alcohol flavor, filter, in the AB-8 macroporous resin of having handled well on the filtrate, respectively with water, 70% ethanol elution, elution volume is 4 times of amounts of column volume, collects 70% ethanol elution, reclaims ethanol, be evaporated to relative density 1.1～1.3 (50 ℃), drying, promptly.Radix Puerariae extract yield by this prepared is 3～5%, and the content of Radix Puerariae total flavones is not less than 70%.
Technology two: get the Radix Puerariae medical material, pulverize, add an amount of moistening of 30% ethanol, pack in the percolator, add 30% alcohol dipping 24 hours, percolation, collect percolate to colourless, being evaporated to does not have the alcohol flavor, filters, in the D201 macroporous resin of having handled well on the filtrate, respectively with water, 15% ethanol, 70% ethanol elution, elution volume is 3 times of amounts of column volume, collect 70% ethanol elution, reclaim ethanol, be evaporated to relative density 1.1～1.3 (50 ℃), drying, promptly.Radix Puerariae extract yield by this prepared is 2～4%, and the content of Radix Puerariae total flavones is not less than 70%.
Technology three: get the Radix Puerariae medical material, pulverize, add 12 times of amounts of 75% ethanol preimpregnation 10 minutes.50 ℃ of supersound extraction then.20 minutes extraction times, 300 watts of power.Solution filters, filtrate recycling ethanol, and being evaporated to relative density is 1.10～1.20 (50 ℃), vacuum drying or spray drying, promptly.Radix Puerariae extract yield by this prepared is 9～12%, and the content of Radix Puerariae total flavones is not less than 50%.
Herba Epimedii in the aforementioned pharmaceutical compositions and Radix Puerariae all can directly be fed intake by the extract of corresponding weight portion and make, is 2～3% according to Herba Epimedii extract with respect to the yield of medical material, Radix Puerariae extract is 3～5% to calculate respectively with respect to the yield of medical material, and the composition of making the crude drug of the contained composition and effectiveness of this pharmaceutical composition can also be 5～240 parts of Herba Epimedii extracts, 3.5～100 parts of Radix Puerariae extracts; Be preferably: 10～120 parts of Herba Epimedii extracts, 7.5～50 parts of Radix Puerariae extracts; More preferably: 20～60 parts of Herba Epimedii extracts, 15～25 parts of Radix Puerariae extracts.In the aforementioned pharmaceutical compositions, the content of Herba Epimedii total flavones is not less than 40% in the Herba Epimedii extract, preferably is not less than 50%, and content Determination of Icariin is not less than 3%; The content of Radix Puerariae total flavones is not less than 50% in the Radix Puerariae extract.
In the aforementioned pharmaceutical compositions, the consumption of drug component is groped to sum up to draw through the inventor in a large number, and each amounts of components all has better curative effect in above-mentioned weight portion scope.Above-mentioned composition as if being unit with the gram, can be made the preparation of 10～1000 consumptions, as tablet, can be made into 10～1000, takes 1～10, every day 1～5 time at every turn; As making 10～1000 as injection, 1～10 of each consumption, every day 1～5 time.Above-mentioned composition is by weight as proportioning, can be raw material with the kilogram as large-scale production, or is unit with the ton, and small-scale production can be unit with the gram also.Above-mentioned parts by weight are for especial patient, and the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
This pharmaceutical composition can be used for preparing the medicine for the treatment of cardiovascular and cerebrovascular disease.The pharmacological effect experimentation shows that this pharmaceutical composition can significantly resist the platelet aggregation effect of COL, ADP, the inductive blood stasis rat of Thro; Enlarge markedly ear arteriole, venule caliber, accelerate blood flow rate; Myocardial ischemia due to the remarkable protection ligation rat coronary artery; Significantly the Acute Myocardial Ischemia in Rats electrocardiogram changes due to the antagonism pituitrin; Significantly remove free radical, the fast shut-off free radical chain reactions suppresses lipid peroxidation, alleviates cerebral tissue protective effects such as delayed cerebral injury; Significantly coronary blood flow increasing increases blood supply of cardiac muscle.Common performance resists myocardial ischemia, coronary blood flow increasing, and antiplatelet aggregation brings high blood pressure down, and improves the blood flow mechanics, improves the cerebrovascular circulation, effects such as anti-hypoxia.
Pharmaceutical composition of the present invention can be made clinically any or pharmaceutically acceptable dosage form with arbitrary mixing acceptable accessories, and preferred oral preparation or injection are applied to the patient who needs this treatment in the mode of oral or parenteral.
When being used for oral administration, conventional solid preparation be can be made into, tablet, capsule, granule, pill and oral solution etc. comprised.Tablet means disk shape or the special-shaped flaky solid preparation that medicine and the auxiliary materials and mixing compacting that suits form; Tablet is based on oral ordinary tablet, and other has buccal tablet, Sublingual tablet, mouth paster, chewable tablet, dispersible tablet, fuse, effervescent tablet, slow releasing tablet, controlled release tablet and enteric coatel tablets etc.Capsule means medicine or is added with the adjuvant filling in Capsules or be sealed in solid preparation in the soft capsule material; Capsule can be divided into hard capsule (being commonly referred to as capsule), soft capsule (soft gelatin capsule), slow releasing capsule, controlled release capsule and enteric coated capsule according to its dissolving and release characteristics.Granule means that medicine and suitable adjuvant make the dried particles shape preparation with certain particle size; Granule can be divided into soluble particles (being commonly referred to as granule), mix suspension grain, effervescent granule, enteric coated particles, slow-releasing granules and controlled release granule etc.Pill means medicine and suitable adjuvant uniform mixing, the spherical or near-spherical solid preparation made from proper method; Pill comprises drop pill, sugar pill, piller etc.Oral solution means that medicine dissolution makes for oral supernatant liquid preparation in suitable solvent.During parenteral, can be made into solution, water for injection or oil-suspending agent, the inhalant etc. of injection.Preferred dosage form is oral formulations such as sheet, capsule, soft capsule, granule, drop pill, oral liquid etc.
When being used for parenteral, can be made into injection.Injection means the intravital solution of confession injection, emulsion or the suspension that medicine is made and supplies to face with preceding preparation or be diluted to solution or the sterile preparation of the powder of suspension or concentrated solution that injection can be divided into injection, injectable sterile powder and concentrated solution for injection.Injection means that the confession that medicine is made is injected into sterile solution type injection, emulsion-type injection or the suspension type injection of using in the body, can be used for intramuscular injection, intravenous injection, intravenous drip etc.; Its specification has 1ml, 2ml, 5ml, 10ml, 20ml, 50ml, 100ml, 200ml, 250ml, 500ml etc., and wherein large volume (generally the being not less than 100ml) injection of using for intravenous drip also claims venous transfusion.Injectable sterile powder means that confession that medicine is made is faced with the suitable sterile solution of preceding usefulness and is mixed with settled solution or the evenly sterilized powder or the aseptic block of suspension, available suitable solvent for injection preparation back injection, also available venous transfusion preparation posterior vein instils; Sterilized powder makes with solvent crystallization, spray drying method or freeze-drying etc.Concentrated solution for injection means that confession that medicine is made faces the aseptic concentrated solution of using for intravenous drip with preceding dilution.
The preparation of pharmaceutical composition of the present invention can adopt the conventional method production in the existing pharmaceutical field, can add various pharmaceutically acceptable carriers when needing.Described carrier comprises osmotic pressure regulator, pH value regulator, solubilizing agent, antioxidant, antibacterial, emulsifying agent, suspending agent, filler, binding agent, disintegrating agent, lubricant of pharmaceutical field routine etc.
When making oral formulations, can add suitable filler, binding agent, disintegrating agent, lubricant etc.Filler comprises starch, Icing Sugar, calcium phosphate, calcium sulfate two water things, dextrin, microcrystalline Cellulose, lactose, pregelatinized Starch, mannitol etc.; Binding agent comprises sodium carboxymethyl cellulose, PVP-K30, hydroxypropyl cellulose, starch slurry, methylcellulose, ethyl cellulose, hypromellose, gelling starch etc.; Disintegrating agent comprises dried starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose etc.; Lubricant comprises magnesium stearate, Pulvis Talci, sodium lauryl sulphate, micropowder silica gel etc.
When making injection, optional use solvent or non-aqueous solvent can add suitable additives according to the character of medicine.The most frequently used aqueous solvent is a water for injection, also available 0.9% sodium chloride solution or other suitable aqueous solutions; Non-aqueous solvent commonly used is a vegetable oil, is mainly the injection soybean oil, and other also have the aqueous solution of ethanol, propylene glycol, Polyethylene Glycol etc.Additives commonly used comprise osmotic pressure regulator, pH value regulator, solubilizing agent, filler, antioxidant, antibacterial, emulsifying agent, suspending agent etc.Osmotic pressure regulator commonly used comprises sodium chloride, glucose, potassium chloride, magnesium chloride, calcium chloride, sorbitol etc., preferred sodium chloride or glucose; PH value regulator commonly used comprises acetic acid-sodium acetate, lactic acid, citric acid-sodium citrate, sodium bicarbonate-sodium carbonate etc.; Solubilizing agent commonly used comprises polyoxyethylene sorbitan monoleate, propylene glycol, lecithin, polyoxyethylene castor oil etc.; Filler commonly used comprises lactose, mannitol, sorbitol, dextran etc.; Antioxidant commonly used has sodium sulfite, sodium sulfite, sodium pyrosulfite etc.; Antibacterial commonly used is phenol, cresol, chlorobutanol etc.Injection container commonly used has glass ampule, vial, plastic ampoule, plastic bottle etc.
The advantage of pharmaceutical composition of the present invention is:
(1) provides Herba Epimedii or its extract and Radix Puerariae or its extract to be used to prepare the compositions for the treatment of cardiovascular and cerebrovascular diseases medicament first, and confirmed that by pharmacological evaluation both have the effect of Synergistic, be better than both independent medications.
(3) the pharmacological effect experimentation shows, this pharmaceutical composition can significantly resist the platelet aggregation effect of COL, ADP, the inductive blood stasis rat of Thro; Enlarge markedly ear arteriole, venule caliber, accelerate blood flow rate; Myocardial ischemia due to the remarkable protection ligation rat coronary artery; Significantly the Acute Myocardial Ischemia in Rats electrocardiogram changes due to the antagonism pituitrin; Significantly remove free radical, the fast shut-off free radical chain reactions suppresses lipid peroxidation, alleviates cerebral tissue protective effects such as delayed cerebral injury; Significantly coronary blood flow increasing increases blood supply of cardiac muscle.Common performance resists myocardial ischemia, coronary blood flow increasing, and antiplatelet aggregation brings high blood pressure down, and improves the blood flow mechanics, improves the cerebrovascular circulation, effects such as anti-hypoxia.Above-mentioned experimental result shows that Herba Epimedii or Herba Epimedii extract and Radix Puerariae or Radix Puerariae extract drug combination have synergism, and drug effect obviously strengthens, and consequently the ordinary person in present technique field institute is beyond thought.
(4) effective ingredient of pharmaceutical composition of the present invention is clear and definite, content is high, and better stability of preparation is convenient to control product quality, can guarantee clinical drug safety.
(5) quality of Herba Epimedii extract and Radix Puerariae extract is controlled, and preferable preparation technique is provided, simple and easy to do, and quality is better, is applicable to industrialized great production.
Below routine by experiment beneficial effect of further setting forth medicine of the present invention, these experimental examples comprise the pharmacodynamic experiment of pharmaceutical composition of the present invention, the pharmaceutical composition that Herba Epimedii or its extract and Radix Puerariae or its extract are prepared from is hereinafter to be referred as YG.Herba Epimedii extract used in the following experimental example all is taken from embodiment 1, and Radix Puerariae extract is all taken from embodiment 2.
Experimental example 1YG is to the influence of blood stasis type rat platelet aggregation
Animal subject: Wistar rat, male and female half and half, body weight 250～300 grams, 140.
Test sample: normal saline: commercial; The Herba Epimedii granule: self-control is equivalent to crude drug 10g; The Radix Puerariae granule: self-control is equivalent to crude drug 5g; YG granule (Herba Epimedii+Radix Puerariae): self-control, parts by weight see Table 1.
Experimental technique: rat is divided into 14 groups at random, 10 every group.Each medicine is mixed with gastric infusion behind the desired concn test liquid with normal saline respectively, and matched group gives isopyknic normal saline.The preparation of rat blood stasis model: except that matched group, all the other are respectively organized respectively at behind the administration last day 1h, subcutaneous injection 0.1% adrenalin hydrochloride 0.08ml/100g, totally 2 times, two minor ticks 4 hours are between the administration (front and back each 2 hours at interval), rat was immersed frozen water 5 minutes, stop eating after the disposal.Detect index: stop eating time morning, each group is used 20% urethane (1g/kg) anesthesia respectively, and 3.8% liquor sodii citratis anticoagulant (1: 9, V/V), from abdominal aortic blood, 1000 commentaries on classics/min, centrifugal 10min gets supernatant, and platelet blood plasma (PRP) is rich in preparation; Surplus 4000 commentaries on classics/min, centrifugal 10min, getting supernatant is platelet poor plasma (PPP).With ADP (1mg/1ml adds 16 μ l), Thro (5U/ml adds 16 μ l), COL (1mg/ml adds 16 μ l) is derivant, measures the platelet maximum agglutination rate with turbidimetry at LBY-NJ blood pool instrument.
Table 1YG to the influence of blood stasis rat platelet aggregation effect (
N=10)
$$P＜0.01 is compared with matched group;
*P＜0.05,
*P＜0.01 is compared with model group.
Experimental result and conclusion: experimental result sees Table 1.
Compare with the blank group, the platelet maximum agglutination rate of model group extremely significantly increases (p＜0.01), and the modeling success is described.Compare with model group, Herba Epimedii group platelet maximum agglutination rate significantly reduces (p＜0.05); Radix Puerariae group platelet maximum agglutination rate significantly reduces (p＜0.05); Each weight proportion group platelet maximum agglutination rate all significantly or extremely significantly reduces (p＜0.05) in 250～8000 parts of Herba Epimedii, 125～2000 parts of scopes of Radix Puerariae, (p＜0.01), and the better effects if that all is better than each weight proportion in single effect, especially 500～4000 parts of Herba Epimedii, 250～1000 parts of scopes of Radix Puerariae with Herba Epimedii or Radix Puerariae.
Each weight proportion all can extremely significantly resist the platelet aggregation effect of COL, ADP, the inductive blood stasis rat of Thro in 250～8000 parts of Herba Epimedii, 125～2000 parts of scopes of Radix Puerariae, effect is better than single with Herba Epimedii and Radix Puerariae, and prompting Herba Epimedii and Radix Puerariae compatibility have the effect of collaborative anticoagulant.
Experimental example 2YG is to microcirculation of mouse auricle influence experiment
Animal subject: male mice, 130, body weight 25～28g.
Test sample: normal saline: commercial; The Herba Epimedii capsule: self-control is equivalent to crude drug 20g; Radix puerariae capsule: self-control is equivalent to crude drug 5g; YG capsule (Herba Epimedii+Radix Puerariae): self-control sees Table 2.
Experimental technique: mice is divided into 13 groups at random, 10 every group.Each medicine is mixed with gastric infusion behind the desired concn test liquid with normal saline respectively, and matched group gives isopyknic normal saline.After the administration, with urethane 1g/kg intraperitoneal injection of anesthesia.Postanesthetic mice places on the supporting plate that is covered with Cotton Gossypii, keeps 20 ± 2 ℃ of room temperatures.Mouse right ear is placed on the ear carriage, on auris dextra, drips a little liquid paraffin, supporting plate is placed on the microscope carrier, regulate cold light source, make illuminating ray and auricle plane at 45～60 ° of angles, and parallel with the direction of growth of hair.Under low power lens, observe the auricle overall picture earlier, select suitable position, use high power lens instead and fix a point to observe continuously.The microcirculating state of 20min after the observation administration, the diameter and the blood flow rate of measurement arteriole, venule.
Table 2YG to microcirculation of mouse auricle influence (
N=10)
*P＜0.05;
*Compare with matched group in p＜0.01.
Experimental result and conclusion: experimental result sees Table 2.
Compare with matched group, Herba Epimedii group, the ear arteriole of Radix Puerariae group mice, venule caliber enlarge markedly (p＜0.05), and blood flow rate is significantly accelerated (p＜0.05); In 250～8000 parts of the Herba Epimedii, 125～2000 parts of scopes of Radix Puerariae the ear arteriole of each weight proportion group mice, venule caliber significantly or the utmost point enlarge markedly (p＜0.05), (p＜0.01), blood flow rate significantly or is extremely significantly accelerated (p＜0.05), (p＜0.01), and the better effects if that all is better than each weight proportion in single effect, especially 500～4000 parts of Herba Epimedii, 250～1000 parts of scopes of Radix Puerariae with Herba Epimedii or Radix Puerariae.
But the equal utmost point of each weight proportion enlarges markedly ear arteriole, venule caliber in 250～8000 parts of Herba Epimedii, 125～2000 parts of scopes of Radix Puerariae, extremely significantly accelerates blood flow rate, and prompting Herba Epimedii and Radix Puerariae compatibility have the effect of collaborative microcirculation improvement.
Experimental example 3YG is to the influence of myocardial ischemia due to the ligation rat coronary artery
Animal subject: Wistar rat, 120, body weight 250～280g, male and female dual-purpose.
Test sample: Herba Epimedii sheet: self-control is equivalent to crude drug 15g; The Radix Puerariae sheet: self-control is equivalent to crude drug 5g; The YG sheet: self-control is equivalent to Herba Epimedii 15g, Radix Puerariae 5g.
Experimental technique: rat is divided into 6 groups at random, 20 every group.Be respectively: myocardial ischemia matched group, Herba Epimedii group, Radix Puerariae group, the basic, normal, high dosage group of YG.Rat is used urethane 1g/kg intraperitoneal injection of anesthesia, back of the body position is fixing, and the record electrocardio connects artificial respirator and practices artificial respiration, open the thoracic cavity, cut off pericardium, each medicine is mixed with gastric infusion behind the desired concn test liquid with normal saline respectively, and the myocardial ischemia matched group gives isopyknic normal saline, behind the administration 3min before the coronary artery of ligation left side branch falls, omnidistance record electrocardio 30min, 1h gets blood after the ligation, detects creatine phosphokinase (CPK) and lactic acid dehydrogenase (LDH).Take out rat heart, with 4 of the even crosscuts of ventricular muscles, 0.5% chlorination nitro tetrazole is blue to dye along ligature, and with the ischemic areas on every myocardium two sides of planimeter survey, the calculating myocardium ischemic areas accounts for the percentage ratio of ventricle area.
Table 3YG to the influence of myocardial ischemia due to the ligation rat coronary artery (
N=20)
*P＜0.05,
*P＜0.01 is compared with the myocardial ischemia matched group;
#P＜0.05 is compared with the Herba Epimedii group;
﹠amp;P＜0.05 is compared with the Radix Puerariae group.
Experimental result and conclusion; Experimental result sees Table 3.After the ligation, the cardiac electrical QRS ripple of myocardial ischemia control rats all increases unusually suddenly, widens, and cardiac muscle is ischemia on a large scale, and biochemistry detection shows as CPK and LDH all increases unusually.Compare with the myocardial ischemia matched group, Herba Epimedii and Radix Puerariae all can significantly reduce extremely significantly to reduce myocardial ischemia scope (p＜0.01) because of the electrocardio due to the ligation coronary artery and the abnormal change (p＜0.05) of biochemical indicator; Each dosage of YG all can extremely significantly reduce extremely significantly to reduce myocardial ischemia scope (p＜0.01) because of the electrocardio due to the ligation coronary artery and the abnormal change (p＜0.01) of biochemical indicator.Each dosage of YG all is better than Herba Epimedii or the individually dosed effect of Radix Puerariae to the protective effect of myocardial ischemia due to the ligation rat coronary artery, and prompting Herba Epimedii and Radix Puerariae drug combination have collaborative function of resisting myocardial ischemia.
Experimental example 4YG is to the research of experimental rat acute myocardial ischemia protective effect
Laboratory animal: the Wistar rat, 70, body weight is at 200～220g, male and female half and half.
Test sample: normal saline, commercial; The Herba Epimedii extract sheet, self-control, 260mg is equivalent to crude drug 10g; The Radix Puerariae extract sheet, self-control, 100mg is equivalent to crude drug 2.5g; The YG sheet, self-control, 360mg contains Herba Epimedii extract 260mg (being equivalent to crude drug 10g), Radix Puerariae extract 100mg (being equivalent to crude drug 2.5g).
Experimental technique: 60 of rats, be divided into 6 groups at random, 10 every group, be respectively the blank group, Herba Epimedii extract group, Radix Puerariae extract group, YG low dose group, dosage group among the YG, YG high dose group.Each medicine is mixed with gastric infusion behind the desired concn test liquid with normal saline respectively, and the blank group gives isopyknic normal saline, administration every day 1 time, continuous 7 days.60min after the last administration in six road physiology monitors (Shanghai medical apparatus factory), connects limb lead and precordial leads with urethanes (1g/kg) intraperitoneal injection of anesthesia, in oscillograph observation and recording ecg.Behind the sublingual vein injection of pituitrin 5 μ l/kg, immediate record V3 electrocardiogram, and respectively trace 1 time in 15s, 30s, 1min, 2min, 5min, respectively organize vein and inject and move on the ECG ST section behind the pituitrin and amplitude that the T ripple raises, and observe each group and ARR number of animals occurs.
Acute Myocardial Ischemia in Rats electrocardiogram variation due to the table 4YG antagonism pituitrin (
N=10)
Annotate:
*P＜0.05,
*P＜0.01 is compared with the blank group.
Experimental result and conclusion: experimental result sees Table 4.Behind the injection of pituitrin, moving on the ST section appears in blank group most animals at once, reaches summit in the 2min, and 5min recovers substantially; Raising appears in ripple in the 2minT, recover gradually, but 5min does not return to normally thereupon; There are 8 rats arrhythmia to occur.Move on the Herba Epimedii extract group ST section and time that the T ripple raise to occur consistent with matched group, but amplitude is significantly less than matched group (p＜0.05); There are 4 rats arrhythmia to occur.Move on the Radix Puerariae extract group ST section and time that the T ripple raise to occur consistent with matched group, but amplitude is significantly less than matched group (p＜0.05); There are 3 rats arrhythmia to occur.Move on each dosage group ST section of YG and time that the T ripple raise to occur consistent with matched group, but amplitude is extremely significantly less than matched group (p＜0.01), and recovers comparatively fast; Low dose group has 2 rats arrhythmia to occur, and middle and high dosage group has 1 rat arrhythmia to occur respectively.Compare with Herba Epimedii extract group, Radix Puerariae extract group, the effect that the anti-electrocardiogram of each dosage of YG changes all is better than single effect with Herba Epimedii extract and Radix Puerariae extract.Prompting Herba Epimedii extract and Radix Puerariae extract drug combination have the collaborative effect that resists myocardial ischemia.
Experimental example 5YG is to the protective effect of rabbit cerebral ischemia perfusion injury
Animal subject: rabbit, 114, the male and female dual-purpose, body weight 2.4～2.8kg is divided at random: ischemia-reperfusion group (18), injection YG organize (18 of each dosage groups), injection Herba Epimedii extract group (18), injection Radix Puerariae extract group (18) and Sham-operated control group (6).
Test sample: sodium chloride injection: commercial; The injection Herba Epimedii extract: self-control, 260mg is equivalent to crude drug 10g; The injection Radix Puerariae extract: self-control, 200mg is equivalent to crude drug 5g; Injection YG: self-control, 460mg contains Herba Epimedii extract 260mg (being equivalent to crude drug 10g), Radix Puerariae extract 200mg (being equivalent to crude drug 5g);
Dosage: test sample all is made into the test liquid of desired concn with sodium chloride injection, the basic, normal, high dosage group of injection YG dosage is followed successively by 20mg/kg, 30mg/kg, 40mg/kg, the dosage of Herba Epimedii group, Radix Puerariae group is 40mg/kg, and ischemia-reperfusion group gives isopyknic sodium chloride injection.
Experimental technique: (1) ischemia-reperfusion group: 18, urethane lipoprotein solution 1g/kg auricular vein anesthesia with 25%, the cervical region median incision separates trachea and inserts tracheal casing pipe, expose bilateral carotid, folder closes both sides tremulous pulse 20min, cause cerebral ischemia, pour into 1,6 and 12h respectively again, each 6 of 3 time points.Behind the pine folder 10min, auricular vein is injected sodium chloride injection.(2) injection YG group: each dosage group is a group greatly, totally 3 groups greatly, 18 of every big groups, the same ischemia-reperfusion group of operation method, each 6 of 3 time points.Behind the pine folder 10min, according to above-mentioned dosage auricular vein bolus infusion YG.(3) injection Herba Epimedii extract group: 18, the same ischemia-reperfusion group of operation method, each 6 of 3 time points.Behind the pine folder 10min, auricular vein bolus infusion Herba Epimedii extract.(4) injection Radix Puerariae extract group: 18, the same ischemia-reperfusion group of operation method, each 6 of 3 time points.Behind the pine folder 10min, auricular vein bolus infusion Radix Puerariae extract.(5) Sham-operated control group: 6, only row anesthesia and tremulous pulse exclusion and not pressing from both sides closed, and puts to death behind the 1h.Above-mentioned each group promptly breaks end after testing and finishing, and strips out brain in ice bath, separates on the ice pan and cuts bilateral hippocampus tissue, is placed in 4 ℃ of refrigerators with the tinfoil parcel to store, and surveys phospholipase A fully
2(PLA
2); Cut cortical tissue and survey brain infarction area, brain water content, the E Ding district tissue specimen of choosing middle cerebral artery blood supply district carries out pathological observation.
Experimental result: (1) is to hippocampal tissue PLA
2Active influence: after ischemia-reperfusion group is poured into 1h, 6h and 12h again, PLA
2Activity extremely significantly increases (p＜0.01) than Sham-operated control group, and prolongs PLA with infusion time
2The activity trend that tapers off, but comparing difference not significantly (p＞0.05) between each time point; (1h, 6h, 12h) PLA of each dosage group of injection YG
2Active significantly reduction relatively has utmost point significant difference (p＜0.01) with each corresponding time point of ischemia-reperfusion group, and with irritating time lengthening, PLA again
2Activity is recovered normal level gradually; Injection Herba Epimedii extract group and injection Radix Puerariae extract group (1h, 6h, 12h) PLA
2The active reduction relatively has significant difference (p＜0.05) with each corresponding time point of ischemia-reperfusion group.
(2) to the influence of cortical tissue's water content (%) and infarct size (%): each time point brain water content of ischemia-reperfusion group all increases; Each each time point brain water content of dosage group group of injection YG is compared with ischemia-reperfusion group and is extremely significantly reduced (p＜0.001), and brain infarction area is compared extremely significantly with ischemia-reperfusion group and dwindled (p＜0.01); Injection Herba Epimedii extract group is compared remarkable reduction (p＜0.05) with each time point brain water content of injection Radix Puerariae extract group with ischemia-reperfusion group, brain infarction area is compared significantly with ischemia-reperfusion group and dwindled (p＜0.05, p＜0.01).
(3) brain tissue pathology change: Sham-operated control group does not have the infarction kitchen range, and the neuronal structure form is normal, continuously the matter edema; Ischemia-reperfusion group has the infarction kitchen range, the neuron swelling of infarction kitchen range week, and cell outline is unclear, and interstitial edema is obvious; Each dosage group of injection YG, injection Herba Epimedii extract group, injection Radix Puerariae extract group infarction kitchen range area all dwindle, and the neuron swelling of infarction kitchen range week is not obvious, and interstitial edema obviously alleviates; The treatment group effect of injection YG is more remarkable.
Conclusion: above-mentioned experimental result shows that behind the cerebral ischemia re-pouring, YG, Herba Epimedii extract, Radix Puerariae extract all can reduce hippocampal tissue PLA
2Activity, improve due to the cerebral ischemia in the environment disorder, alleviate cerebral edema, reduce brain infarction area; Illustrate that YG, Herba Epimedii extract, Radix Puerariae extract all have the removing free radical, the fast shut-off free radical chain reactions suppresses lipid peroxidation, alleviates cerebral tissue protective effects such as delayed cerebral injury.Each dosage of injection YG drug effect in every index all is higher than the effect of injection Herba Epimedii extract and the independent medication of injection Radix Puerariae extract, points out two medicine compatibilities to have synergistic function, and cerebral ischemia reperfusion injury is had remarkable protective effect.
[specific embodiment]
The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.The adjuvant of each dosage form can replace with acceptable accessories in following examples, perhaps reduces, increases.
The preparation and the assay of embodiment 1 Herba Epimedii extract
1, the preparation of Herba Epimedii extract
Get epimedium herb 1000g, be ground into middle powder, add 12 times of amounts of 70% ethanol, soaked 12 hours, filter filtrate for later use; Medicinal residues add 70% ethanol heating extraction three times, each 1.5 hours, filter, merging filtrate, filtrate decompression is concentrated into 1000ml, on the D101 macroporous resin column handled well, earlier with distilled water 4L eluting, reuse 25% ethanol 3L eluting, use 70% ethanol 15L eluting at last, collect 70% ethanol elution, decompression recycling ethanol, vacuum drying, promptly.
Prepare three batches of Herba Epimedii extracts according to the method described above respectively, yield sees Table 5.
2, the assay of Herba Epimedii extract
The assay of Herba Epimedii total flavones
The algoscopy precision takes by weighing Herba Epimedii extract 0.01g, puts in the 50ml measuring bottle, adds methanol 25ml supersound process 30 minutes, adds methanol and is diluted to scale, shakes up, as need testing solution.Other gets the icariin reference substance, adds methanol and makes the solution that every 1ml contains 10 μ g, in contrast product solution.Getting need testing solution and reference substance solution respectively, is blank with the corresponding reagent, according to ultraviolet visible spectrophotometry (appendix VA of Chinese Pharmacopoeia version in 2005), measures absorbance at 270nm wavelength place, calculates, promptly.
Content Determination of Icariin is measured
Chromatographic condition and system suitability test are filler with the octadecyl silane; With second eyeball-water (30: 70) is mobile phase; The detection wavelength is 270nm.Number of theoretical plate calculates by the icariin peak and is not less than 1500.
Reference substance solution must prepare precision, and to take by weighing the icariin reference substance an amount of, adds methanol and make the solution that every 1ml contains 0.1mg, promptly.
The preparation Herba Epimedii extract 20mg of need testing solution, the accurate title, decide, and puts in the 100ml measuring bottle, adds Diluted Alcohol and make dissolving in right amount, and be diluted to scale with Diluted Alcohol, shakes up, and filters, and gets subsequent filtrate, promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Three batches of Herba Epimedii extracts to above-mentioned preparation carry out assay respectively, and measurement result sees Table 5.
The assay result and the yield of table 5 Herba Epimedii extract
The preparation and the assay of embodiment 2 Radix Puerariae extracts
1, the preparation of root extract
Get the Radix Puerariae medical material, pulverize, add 70% alcohol heating reflux and extract twice, add 12 times of amounts of alcohol for the first time, extracted 2 hours, and added 10 times of amounts of alcohol for the second time, extracted 1 hour, merge extractive liquid, filters, and filtrate is concentrated into does not have the alcohol flavor, filter, in the AB-8 macroporous resin of having handled well on the filtrate, respectively with water, 70% ethanol elution, elution volume is 4 times of amounts of column volume, collects 70% ethanol elution, reclaims ethanol, be evaporated to relative density 1.1～1.3 (50 ℃), drying, promptly.
2, Radix Puerariae extract assay
The assay of Radix Puerariae total flavones
The preparation precision of reference substance solution takes by weighing in control substance of Rutin 10mg, puts in the 25ml measuring bottle, adds 80% dissolve with ethanol, standardize solution.
The preparation precision of standard curve is measured reference substance solution 0ml, 0.2ml, 0.4ml, 0.6ml, 0.8ml, 1.0ml put in the 10ml measuring bottle, add 5% sodium nitrite 0.3ml, placed 6 minutes, add 4% sodium hydroxide 4ml, water is diluted to scale, shakes up. carry out full wavelength scanner, at the 510nm place absorption maximum is arranged, absorbance with mensuration is vertical coordinate (y), and the concentration of reference substance (μ g/ml) is abscissa (x), the drawing standard curve.
The preparation precision of need testing solution takes by weighing Radix Puerariae extract 25mg, puts in the 25ml measuring bottle, adds ethanol to scale, shakes up, and the accurate 5ml that draws puts in the 25ml measuring bottle, adds water to scale, shakes up, promptly.
The algoscopy precision is measured need testing solution 2ml, puts in the 25ml nessler colorimetric tube, measures absorbance in accordance with the law, from the amount that standard curve is read flavone the need testing solution, calculates, promptly.
Three batches of Radix Puerariae extracts to above-mentioned preparation carry out assay respectively, and measurement result sees Table 6.
The assay result and the yield of table 6 Radix Puerariae extract
The preparation of embodiment 3YG tablet
Prescription one:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 168g (being equivalent to crude drug 4000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription two:
Herba Epimedii extract 13g (being equivalent to crude drug 500g)
Radix Puerariae extract 21g (being equivalent to crude drug 500g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription three:
Herba Epimedii extract 13g (being equivalent to crude drug 500g)
Radix Puerariae extract 42g (being equivalent to crude drug 1000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription four:
Herba Epimedii extract 13g (being equivalent to crude drug 500g)
Radix Puerariae extract 84g (being equivalent to crude drug 2000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription five:
Herba Epimedii extract 13g (being equivalent to crude drug 500g)
Radix Puerariae extract 168g (being equivalent to crude drug 4000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription six:
Herba Epimedii extract 26g (being equivalent to crude drug 1000g)
Radix Puerariae extract 10.5g (being equivalent to crude drug 250g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Prescription seven:
Herba Epimedii extract 26g (being equivalent to crude drug 1000g)
Radix Puerariae extract 21g (being equivalent to crude drug 500g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 40g
Low-substituted hydroxypropyl cellulose 40g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 12g
Prepare 1000 altogether
Preparation technology:
(1) it is standby Herba Epimedii extract and Radix Puerariae extract to be pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) hypromellose 2% the aqueous solution made soluble in water is standby.
(4) with Radix Puerariae extract, Herba Epimedii extract, pregelatinized Starch, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
(5) cross 20 mesh sieve system granules.
(6) granule is dried under 60 ℃ condition.
(7) dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously.
(8) sampling, the semi-finished product chemical examination.
(9) the sheet weight sheet of determining according to chemical examination.
(10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 4YG capsule
Prescription one:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 84g (being equivalent to crude drug 2000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Prescription two:
Herba Epimedii extract 26g (being equivalent to crude drug 1000g)
Radix Puerariae extract 84g (being equivalent to crude drug 2000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Prescription three:
Herba Epimedii extract 26g (being equivalent to crude drug 1000g)
Radix Puerariae extract 168g (being equivalent to crude drug 4000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Prescription four:
Herba Epimedii extract 52g (being equivalent to crude drug 2000g)
Radix Puerariae extract 10.5g (being equivalent to crude drug 250g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Prescription five:
Herba Epimedii extract 52g (being equivalent to crude drug 2000g)
Radix Puerariae extract 21g (being equivalent to crude drug 500g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Prescription six:
Herba Epimedii extract 52g (being equivalent to crude drug 2000g)
Radix Puerariae extract 42g (being equivalent to crude drug 1000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Prescription seven:
Herba Epimedii extract 52g (being equivalent to crude drug 2000g)
Radix Puerariae extract 84g (being equivalent to crude drug 2000g)
Pregelatinized Starch 120g
Microcrystalline Cellulose 50g
Low-substituted hydroxypropyl cellulose 30g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Prepare 1000 altogether
Preparation technology:
(1) it is standby Herba Epimedii extract and Radix Puerariae extract to be pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) hypromellose 2% the aqueous solution made soluble in water is standby.
(4) with Radix Puerariae extract, Herba Epimedii extract, pregelatinized Starch, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material.
(5) cross 20 mesh sieve system granules.
(6) granule is dried under 60 ℃ condition.
(7) dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously.
(8) sampling, the semi-finished product chemical examination.
(9) loading amount of determining according to chemical examination incapsulates.
(10) finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 5YG granule
Prescription one:
Herba Epimedii extract 52g (being equivalent to crude drug 2000g)
Radix Puerariae extract 168g (being equivalent to crude drug 4000g)
Icing Sugar 2000g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription two:
Herba Epimedii extract 104g (being equivalent to crude drug 4000g)
Radix Puerariae extract 10.5g (being equivalent to crude drug 250g)
Icing Sugar 2000g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription three:
Herba Epimedii extract 104g (being equivalent to crude drug 4000g)
Radix Puerariae extract 21g (being equivalent to crude drug 500g)
Icing Sugar 2000g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription four:
Herba Epimedii extract 104g (being equivalent to crude drug 4000g)
Radix Puerariae extract 42g (being equivalent to crude drug 1000g)
Icing Sugar 2000g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription five:
Herba Epimedii extract 104g (being equivalent to crude drug 4000g)
Radix Puerariae extract 84g (being equivalent to crude drug 2000g)
Icing Sugar 2000g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription six:
Herba Epimedii extract 104g (being equivalent to crude drug 4000g)
Radix Puerariae extract 168g (being equivalent to crude drug 4000g)
Icing Sugar 2000g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription seven:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 10.5g (being equivalent to crude drug 250g)
Icing Sugar 2000g
Steviosin 15g
Fructus Citri Limoniae essence is an amount of
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Preparation technology:
(1) it is standby sucrose to be pulverized 80 mesh sieves; It is standby that Herba Epimedii extract and Radix Puerariae extract were pulverized 100 mesh sieves.
(2) take by weighing raw material and adjuvant according to recipe quantity.
(3) the method mix homogeneously that Herba Epimedii extract, Radix Puerariae extract and Icing Sugar, steviosin are progressively increased with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material,
(4) cross 20 mesh sieve system granules.
(5) granule is dried under 60 ℃ condition.
(6) dried granule is crossed 18 mesh sieve granulate, sprays into an amount of Fructus Citri Limoniae essence.
(7) sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule.
(8) packing, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 6YG oral liquid
Prescription one:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 21g (being equivalent to crude drug 500g)
Propylene glycol 1000ml
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 10000ml
Prepare 1000 altogether
Prescription two:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 42g (being equivalent to crude drug 1000g)
Propylene glycol 1000ml
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 10000ml
Prepare 1000 altogether
Prescription three:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 84g (being equivalent to crude drug 2000g)
Propylene glycol 1000ml
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 10000ml
Prepare 1000 altogether
Prescription four:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 168g (being equivalent to crude drug 4000g)
Propylene glycol 1000ml
Sodium benzoate 15g
Stevioside 10g
Purified water adds to 10000ml
Prepare 1000 altogether
Preparation technology:
(1) fully with heated and stirred dissolving in the purified water of Radix Puerariae extract and Herba Epimedii extract adding dosing amount 50%; It is complete to add the propylene glycol stirring and dissolving again.
(2) sodium benzoate and stevioside is complete with the water dissolution of dosing amount 20%.
(3) merge above-mentioned solution, add purified water to full dose.
(4) filtering with microporous membrane of mistake 0.8 μ m.
(5) semi-finished product chemical examination.
(6) fill, finished product is examined entirely, the packing warehouse-in.
The preparation of embodiment 7YG injection
Prescription one:
Herba Epimedii extract 13g (being equivalent to crude drug 500g)
Radix Puerariae extract 10.5g (being equivalent to crude drug 250g)
Polyoxyethylene sorbitan monoleate 100g
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription two:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 10.5g (being equivalent to crude drug 250g)
Polyoxyethylene sorbitan monoleate 100g
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription three:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 21g (being equivalent to crude drug 500g)
Polyoxyethylene sorbitan monoleate 100g
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription four:
Herba Epimedii extract 208g (being equivalent to crude drug 8000g)
Radix Puerariae extract 42g (being equivalent to crude drug 1000g)
Polyoxyethylene sorbitan monoleate 100g
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription five:
Herba Epimedii extract 26g (being equivalent to crude drug 1000g)
Radix Puerariae extract 42g (being equivalent to crude drug 1000g)
Polyoxyethylene sorbitan monoleate 100g
Water for injection adds to 5000ml
Prepare 1000 altogether
Concrete steps:
(1) carries and handle the previous day such as pipeline that dosing uses and container etc., face with the fresh water for injection flushing of preceding reuse;
(2) polyoxyethylene sorbitan monoleate is made 20% aqueous solution, added the Herba Epimedii extract and the Radix Puerariae extract of recipe quantity, the heated and stirred dissolving fully;
(3) benefit adds to the full amount of water for injection;
(4) needle-use activated carbon of adding dosing amount 0.1%, heated and stirred 15 minutes;
(5) through sand filtration rod filtering decarbonization, measure the also pH value of regulator solution;
(6) through the microporous filter membrane fine straining of 0.45 μ m;
(7) clarity of inspection solution, the semi-finished product chemical examination;
(8) with the solution sealing by fusing in glass ampule;
(9) 100 ℃ of flowing steam sterilizations 30 minutes;
(10) while hot sample being put into 0.01% methylene blue solution hunts leak;
(11) lamp inspection, finished product is examined entirely, the packing warehouse-in.
Claims (10)
1. a pharmaceutical composition that is used for cardiovascular and cerebrovascular disease is characterized in that, calculates according to composition by weight, makes the consisting of of crude drug of the contained active ingredient of this pharmaceutical composition: 250～8000 parts of Herba Epimedii, 125～2000 parts of Radix Puerariaes.
2. pharmaceutical composition according to claim 1 is characterized in that, calculates according to composition by weight, makes the consisting of of crude drug of the contained active ingredient of this pharmaceutical composition: 500～4000 parts of Herba Epimedii, 250～1000 parts of Radix Puerariaes.
3. pharmaceutical composition according to claim 2 is characterized in that, calculates according to composition by weight, makes the consisting of of crude drug of the contained active ingredient of this pharmaceutical composition: 1000～2000 parts of Herba Epimedii, 500 parts of Radix Puerariaes.
4. according to the described arbitrary preparation of drug combination method of claim 1～3, it is characterized in that, described Herba Epimedii and Radix Puerariae can be with The suitable solvent respectively or mix through extracting processing and obtain its extract, total extract is made preparation with the pharmaceutic adjuvant hybrid process again, and the main effective ingredient of gained total extract is a flavone compound.
5. pharmaceutical composition according to claim 1 is characterized in that, calculate according to composition by weight, and the composition of making the crude drug of the contained composition and effectiveness of this pharmaceutical composition can also be 5～240 parts of Herba Epimedii extracts, 3.5～100 parts of Radix Puerariae extracts.
6. pharmaceutical composition according to claim 5 is characterized in that, calculates according to composition by weight, makes the consisting of of crude drug of the contained composition and effectiveness of this pharmaceutical composition: 10～120 parts of Herba Epimedii extracts, 7.5～50 parts of Radix Puerariae extracts.
7. pharmaceutical composition according to claim 6 is characterized in that, calculates according to composition by weight, makes the consisting of of crude drug of the contained composition and effectiveness of this pharmaceutical composition: 20～60 parts of Herba Epimedii extracts, 15～25 parts of Radix Puerariae extracts.
8. according to the described arbitrary pharmaceutical composition of claim 5～7, it is characterized in that the content of Herba Epimedii total flavones is not less than 40% in the described Herba Epimedii extract, content Determination of Icariin is not less than 3%; The content of Radix Puerariae total flavones is not less than 50% in the Radix Puerariae extract.
9. according to claim 1～3,5～7 described arbitrary pharmaceutical compositions, it is characterized in that this pharmaceutical composition can be made clinically any or pharmaceutically acceptable dosage form with arbitrary mixing acceptable accessories.
10. pharmaceutical composition according to claim 9 is characterized in that, described dosage form is oral formulations or injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100693937A CN101167784A (en) | 2006-10-25 | 2006-10-25 | Medicinal composition for cardiovascular and cerebrovascular diseases |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100693937A CN101167784A (en) | 2006-10-25 | 2006-10-25 | Medicinal composition for cardiovascular and cerebrovascular diseases |
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| CN101167784A true CN101167784A (en) | 2008-04-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNA2006100693937A Pending CN101167784A (en) | 2006-10-25 | 2006-10-25 | Medicinal composition for cardiovascular and cerebrovascular diseases |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104644901A (en) * | 2015-02-02 | 2015-05-27 | 万光瑞 | Chinese medicinal preparation for long-term prevention and treatment of cardiovascular and cerebrovascular diseases at remission stage and preparation method of Chinese medicinal preparation |
| CN112552356A (en) * | 2020-06-29 | 2021-03-26 | 郑州福瑞堂制药有限公司 | Method for preparing icariin |
-
2006
- 2006-10-25 CN CNA2006100693937A patent/CN101167784A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104644901A (en) * | 2015-02-02 | 2015-05-27 | 万光瑞 | Chinese medicinal preparation for long-term prevention and treatment of cardiovascular and cerebrovascular diseases at remission stage and preparation method of Chinese medicinal preparation |
| CN112552356A (en) * | 2020-06-29 | 2021-03-26 | 郑州福瑞堂制药有限公司 | Method for preparing icariin |
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