CN101190254B - Medicinal composition containing kudzu root or its extract and mongolian snakegourd or its extract - Google Patents
Medicinal composition containing kudzu root or its extract and mongolian snakegourd or its extract Download PDFInfo
- Publication number
- CN101190254B CN101190254B CN2006100702796A CN200610070279A CN101190254B CN 101190254 B CN101190254 B CN 101190254B CN 2006100702796 A CN2006100702796 A CN 2006100702796A CN 200610070279 A CN200610070279 A CN 200610070279A CN 101190254 B CN101190254 B CN 101190254B
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- extract
- fructus trichosanthis
- radix puerariae
- parts
- pharmaceutical composition
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Abstract
The invention belongs to the field of medicine technology, particularly relating to a medicine composition used for treating cardiovascular disease, the preparation method and usage thereof as well as the preparations containing the medicine composition. The composition of the raw materials of the effective components of the medicine composition is: 125-2000 portions of kudzuvine root and 100-2000 portions of snakegourd fruit, or 4-100 portions of kudzuvine root extract and 2-160 portions of snakegourd fruit extract. The medicine composition can be prepared into any preparation formulation acceptable in pharmacy, but injection or oral preparation is preferred. The medicine composition of the invention has the functions of dilatating coronary, increasing the flow rate of coronary, inhibiting platelet aggregation, decreasing blood viscosity, reducing the formation of thrombus through improving hemorheology and microcirculation, improving the blood supply function of the heart, reducing cerebral vascular resistance, increasing cerebral vascular blood flow, improving the microcirculation of the brain, etc.
Description
[technical field]
The invention belongs to medical technical field, be specifically related to a kind of pharmaceutical composition that is used for cardiovascular and cerebrovascular disease and preparation method thereof, and the preparation that contains this pharmaceutical composition.
[background technology]
Cardiovascular and cerebrovascular disease is the No.1 disease that threatens middle-aged and elderly people, and mostly its sickness rate height, disability rate height, mortality rate height and complication are typically " more than the three-hypers one " disease, has brought great harm for patient and family, society.It also is one of principal disease of present harm humans health and lives.In China, nineteen fifty-seven the national then total disease death number because of the dead number of this disease accounts for 10.07%, by 1997, this numeral then rose to 39%, and had the satisfactory cerebrovascular disease death of report to account for total death toll nearly 50% at present.These numerals highlight the serious threat of cardiovascular and cerebrovascular disease to us.
Yet the development rate of China's cardiovascular and cerebrovascular medicine is far away from the high incidence of cardiovascular and cerebrovascular disease at present, therefore press for the effectively medicine of treatment cardiovascular and cerebrovascular disease of exploitation, and the toxic and side effects of chemicals is big, easily develop immunity to drugs, therefore researching and developing new Chinese medicine evident in efficacy, low toxicity is the direction that the personage of the world of medicine is devoted to develop.
Radix Puerariae is the dry root of legume pueraria lobata Pueraria lobata (Willd.) Ohwi, practises claiming 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 is a Radix Puerariae total flavones, mainly contains puerarin, daidzein, daidzin, seven material lignin etc.Radix Puerariae has the effect of blood circulation promoting and blood stasis dispelling expansion peripheral blood vessel.Modern study confirms that puerarin has beta-receptor retardation widely, decreased heart rate, reduce myocardial oxygen consumption, coronary dilating, blood fat reducing, improve high blood viscosity and anticoagulant, microcirculation improvement and antiplatelet aggregation are removed free radical, alleviating vascular spasm in addition, are stablized effects such as atherosclerotic plaque.
Fructus Trichosanthis is the dry fruit of calabash plant Fructus Trichosanthis Trichosanthes kirilowii Maxim or trichosanthes rosthornii Harms Trichosanthes rosthorniiHarms, and the beginning is stated from Shennong's Herbal.Mainly contain number of chemical compositions such as oils and fats, organic acid, sterol, triterpene and glycoside thereof, protein, amino acids and trace element, water soluble polysaccharide.Modern study shows, Fructus Trichosanthis energy coronary artery dilator, and coronary blood flow increasing increases myocardial contraction, the expansion blood capillary, antiplatelet aggregation improves hypoxia-bearing capability, can blood fat reducing, reduce effects such as serum cholesterol, angina pectoris, coronary heart disease there are better curative effect.
Utilize the interaction of Radix Puerariae or its extract and Fructus Trichosanthis or its 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]
The purpose of this invention is to provide a kind of pharmaceutical composition that is used for cardiovascular and cerebrovascular disease and its production and use, and the preparation that contains this pharmaceutical composition.
Calculate according to composition by weight, the crude drug of making the contained composition and effectiveness of pharmaceutical composition of the present invention is: 125～2000 parts of Radix Puerariaes, 100～2000 parts of Fructus Trichosanthis, prove that through a large amount of screening experiment of inventor pharmaceutical composition of the present invention all has the effect of Synergistic in above-mentioned weight portion scope; Be preferably: 250～1000 parts of Radix Puerariaes, 500～1500 parts of Fructus Trichosanthis; More preferably: 500 parts of Radix Puerariaes, 1000 parts of Fructus Trichosanthis.
Radix Puerariae in the pharmaceutical composition of the present invention and Fructus Trichosanthis can be with The suitable solvent and method respectively or mix through extracting processing and obtain its extract, and total extract is made any preparation with the pharmaceutic adjuvant hybrid process again.Described solvent is meant solvent pharmaceutically commonly used, preferred water or alcohol, and extracting method can extract with pharmaceutically conventional method, as infusion process, percolation, decocting method, reflux extraction, continuous extraction etc.The main effective ingredient of gained total extract is flavonoid and steroid compound.
The invention provides the preferred extraction process of Radix Puerariae, specific as follows:
Technology one: get the Radix Puerariae medical material, pulverize, add 70% alcohol heating reflux and extract secondary, 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, in the percolator of packing into, add 30% alcohol dipping 24 hours, percolation is collected percolate to colourless, and being evaporated to does not have the alcohol flavor, filters the D that has handled well on the filtrate
201In the macroporous resin, respectively with water, 15% ethanol, 70% ethanol elution, elution volume is 3 times of amounts of column volume, collects 70% ethanol elution, reclaims ethanol, is 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%.
Radix Puerariae in the pharmaceutical composition of the present invention can extract preparation by above-mentioned technology, but is not limited only to above-mentioned technology.
The invention provides the preferred extraction process of Fructus Trichosanthis, specific as follows:
Get the Fructus Trichosanthis medical material, oven dry is ground into coarse powder, add entry reflux, extract, secondary, add 10 times of water gagings at every turn, reflux, extract, 2 hours, filter, merging filtrate, being concentrated into relative density is the concentrated solution of 1.10～1.15 (60 ℃), add ethanol and reach 80% to containing the alcohol amount, placement is spent the night, and gets supernatant, reclaim ethanol to there not being the alcohol flavor, be decompressed to the thick paste shape, vacuum drying, promptly.Fructus Trichosanthis extract yield by this prepared is 6～8%, and wherein the steroid compound total content is not less than 10%.
In order to make pharmaceutical composition of the present invention reach better therapeutic, also can above-mentioned Fructus Trichosanthis extract is further refining: with above-mentioned technology obtain the Fructus Trichosanthis crude extract with the suitable quantity of water dissolving after, extract secondary with the jolting of equivalent petroleum ether, water liquid extracts three times with the jolting of equivalent water-saturated n-butanol, merge n-butanol extracting liquid, be concentrated into dried, residue adds low amounts of water makes dissolving, last macroporous resin column, water, 15% ethanol, 70% ethanol elution are collected 70% ethanol elution respectively, decompression recycling ethanol, be concentrated into the thick paste shape, spray drying, promptly.Fructus Trichosanthis extract yield by this prepared is 2～4%, and wherein the steroid compound total content is not less than 30%.
Fructus Trichosanthis in the pharmaceutical composition of the present invention can extract preparation by above-mentioned technology, but is not limited only to above-mentioned technology.
Radix Puerariae in the pharmaceutical composition of the present invention and Fructus Trichosanthis also can directly be fed intake by the extract of corresponding weight portion and make, is 3～5% according to Radix Puerariae extract with respect to the yield of medical material, the yield that Fructus Trichosanthis extract is equivalent to medical material is 2～8% to calculate respectively, and the composition of making the crude drug of the contained composition and effectiveness of this pharmaceutical composition can also be 4～100 parts of Radix Puerariae extracts, 2～160 parts of Fructus Trichosanthis extracts; Be preferably: 7.5～50 parts of Radix Puerariae extracts, 10～120 parts of Fructus Trichosanthis extracts; More preferably: 15～25 parts of Radix Puerariae extracts, 20～80 parts of Fructus Trichosanthis extracts.The content of Radix Puerariae total flavones is not less than 50% in the Radix Puerariae extract, preferably is not less than 70%; The content of steroid compound is not less than 10% in the Fructus Trichosanthis extract, preferably is not less than 30%.
The consumption of each drug component is groped to sum up to draw through the inventor in a large number in the aforementioned pharmaceutical compositions, and the consumption of each component all has better curative effect in above-mentioned weight range.More than form,, can make the preparation of 10～1000 consumptions,, can be made into 100～10000,1～10 of each consumption, every day 1～5 time as injection as if being unit with the gram.As tablet, can be made into 100～10000, take 1～10, every day 1～5 time at every turn.Its composition can or reduce according to the corresponding proportion increase when producing by weight as proportioning, can be raw material with the kilogram as large-scale production, or be unit with the ton, small-scale production can be unit with the gram also, and weight can increase or reduce, but the weight proportion between each composition is constant.
Above ratio obtains through science screening, and for especial patient, the ratio of can corresponding adjustment forming increases or reduce being no more than 100%.
The application of the further claimed pharmaceutical composition of the present invention of the present invention in the medicine of preparation treatment cardiovascular and cerebrovascular disease.Pharmacological evaluation shows, pharmaceutical composition of the present invention can coronary artery dilator, increases coronary flow; Can anticoagulant, blood viscosity lowering, thus improve hemorheology and microcirculation reduces thrombosis; Improve the heart blood supply function, reduce cerebral vascular resistance, increase cerebrovascular flow, improve brain microcirculation; Can be used for coronary heart disease, angina pectoris, ischemic cerebrovascular, and apoplexy and apoplexy sequela etc.
Pharmaceutical composition of the present invention can be made clinically any or pharmaceutically acceptable dosage form, optimizing injection or oral formulations with acceptable accessories; Can parenteral or mode such as oral administration be applied to the patient who needs this treatment.
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.
When making injection, can adopt the conventional method production in the existing pharmaceutical field, optional use solvent or non-aqueous solvent.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.During the preparation injection, can add suitable additives according to the character of medicine, as 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.
Be used for when oral, can be made into conventional solid preparation, as tablet, capsule, pill, granule etc.; Also can be made into oral liquid, as oral solution, oral suspensions, syrup etc.Tablet means disk shape or the special-shaped flaky solid preparation that medicine and the auxiliary materials and mixing compacting that suits form, based on oral ordinary tablet, 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, according to its dissolving and release characteristics, 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 etc.Pill means medicine and suitable adjuvant uniform mixing, and the spherical or near-spherical solid preparation so that proper method is made comprises drop pill, sugar pill, piller etc.Granule means that medicine and suitable adjuvant make the dried particles shape preparation with certain particle size, 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.Oral solution means that medicine dissolution makes for oral supernatant liquid preparation in suitable solvent.Oral suspensions means the slightly solubility solid drugs, is dispersed in the liquid medium, makes for oral suspension body preparation, also comprises dry suspension or dense suspension.Syrup means the dense aqueous sucrose solution that contains medicine.
When making oral formulations, can add suitable filler, binding agent, disintegrating agent, lubricant etc.Filler commonly used comprises starch, Icing Sugar, calcium phosphate, calcium sulfate two water things, dextrin, microcrystalline Cellulose, lactose, pregelatinized Starch, mannitol etc.; Typical binders comprises sodium carboxymethyl cellulose, PVP-K30, hydroxypropyl cellulose, starch slurry, methylcellulose, ethyl cellulose, hypromellose, gelling starch etc.; Disintegrating agent commonly used comprises dried starch, polyvinylpolypyrrolidone, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose etc.; Conventional lubricants comprises magnesium stearate, Pulvis Talci, sodium lauryl sulphate, micropowder silica gel etc.
The advantage of pharmaceutical composition of the present invention is:
(1) adopts Radix Puerariae or its extract and Fructus Trichosanthis or its extract compatibility to be used to prepare the medicine for the treatment of cardiovascular and cerebrovascular disease first, and confirm that by pharmacological evaluation both have the effect of Synergistic, be better than both independent medications.
(2) consumption to pharmaceutical composition Chinese medicine component of the present invention has carried out pharmacodynamic experiment research, to the influence of ligation bilateral common carotid arteries survival of rats rate and to the microcirculation of mouse auricle influence, screening draws the weight proportion scope with significant curative effect by research pharmaceutical composition of the present invention.
(3) the pharmacological effect experimentation shows, pharmaceutical composition of the present invention has remarkable protective effect to rat acute ischemic anoxia disturbance of cerebral circulation due to the ligation bilateral common carotid arteries; Can enlarge markedly Mice Auricle arteriole, venule caliber, significantly accelerate blood flow rate; Effect with remarkable Chinese People's Anti-Japanese Military and Political College Mus myocardial ischemia; Significantly reduce the platelet maximum agglutination rate of rat, anti thrombotic action is arranged; The Medulla Leporis seu Oryctolagi ischemical reperfusion injury there is remarkable protective effect.Experimental result proves that Radix Puerariae or its extract and Fructus Trichosanthis or its extract drug combination are synergism, and drug effect obviously strengthens, the dose-effect relationship distinctness, and institute reaches effect, is that those of ordinary skills institute is beyond thought.
(4) effective ingredient of pharmaceutical composition of the present invention is clear and definite, content is high, is convenient to control product quality, can guarantee clinical drug safety.
(5) quality of Radix Puerariae extract and Fructus Trichosanthis 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 pharmaceutical composition of the present invention, these experimental examples comprise the pharmacological effect experiment of pharmaceutical composition of the present invention.Pharmaceutical composition of the present invention has following beneficial effect, but this should be interpreted as that pharmaceutical composition of the present invention only has following beneficial effect.
Radix Puerariae extract used in the following experimental example is all with reference to the preparation of the Radix Puerariae extract preparation method among the embodiment 1, and Fructus Trichosanthis extract all prepares with reference to the Fructus Trichosanthis extract preparation method among the embodiment 2.
Experimental example 1 pharmaceutical composition of the present invention is to the influence of survival of rats time of ligation bilateral common carotid arteries
Animal subject: male rat, body weight 200～250g, is divided into 16 groups at random by 160.
Test sample: Radix Puerariae sheet: self-control is equivalent to crude drug 2.5g;
The Fructus Trichosanthis sheet: self-control is equivalent to crude drug 5g;
The compositions sheet: self-control, the different proportionings of the present composition see Table 1.
Experimental technique: rat is divided into 16 groups at random, 10 every group, is respectively normal saline matched group, Radix Puerariae group, Fructus Trichosanthis group, the different proportioning groups of compositions.Each administration group medicine all becomes suitable concentration with distilled water diluting before administration.
Each organizes equal one week of gastric infusion of rat, and once a day, the matched group gastric infusion is with the volume normal saline, and 20min separates bilateral common carotid arteries with urethane 1.3g/kg intraperitoneal injection of anesthesia after the last administration, and live time recorded in the ligation postscript.Experimental result sees Table 1.
Table 1 pharmaceutical composition of the present invention to the influence of ligation bilateral common carotid arteries survival of rats rate (X ± S, n=10)
Annotate: compare with the normal saline matched group,
*P＜0.05; Compare with the Radix Puerariae group,
#P＜0.05; Compare with the Fructus Trichosanthis group,
﹠amp;P＜0.05.
Experimental result: by last table experimental result as can be known,
Compare with the normal saline matched group, Radix Puerariae and Fructus Trichosanthis be the energy significant prolongation survival of rats time (p＜0.05) all; The equal energy significant prolongation survival of rats time (p＜0.05) of each proportioning compositions in 125～2000 parts of Radix Puerariaes, 100～2000 parts of scopes of Fructus Trichosanthis, the effect of each proportioning is more obvious in 250～1000 parts of Radix Puerariaes, 500～1500 parts of scopes of Fructus Trichosanthis, and is best with the effect of 500 parts of Radix Puerariaes, 1000 parts of Fructus Trichosanthis.Compare the effect of each proportioning compositions group more remarkable (p＜0.05) with Radix Puerariae or Fructus Trichosanthis group.
Conclusion: as can be known by above-mentioned experimental result; but each administration group gastric infusion is the time-to-live of significant prolongation bilateral ligation rat all; and the effect of each proportioning compositions group is better than single with Radix Puerariae or Fructus Trichosanthis group; prompting; Radix Puerariae and Fructus Trichosanthis drug combination; have synergistic function, rat acute ischemic anoxia disturbance of cerebral circulation due to the ligation bilateral common carotid arteries is had remarkable protective effect.
Experimental example 2 pharmaceutical compositions of the present invention are to microcirculation of mouse auricle influence experiment
Animal subject: male mice, 150, body weight 25～28g.
Test sample: sodium chloride injection: commercial; GEGEN ZHUSHEYE: self-control is equivalent to crude drug 5g; The Fructus Trichosanthis injection: self-control is equivalent to crude drug 5g; Composite injection (Radix Puerariae+Fructus Trichosanthis): self-control sees Table 2.
Experimental technique: mice is divided into 15 groups at random, 10 every group.Each medicine is mixed with desired concn test liquid pneumoretroperitoneum drug administration by injection with sodium chloride injection respectively, and matched group gives isopyknic sodium chloride injection.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 2 pharmaceutical composition of the present invention to microcirculation of mouse auricle influence (x ± s, n=10)
Annotate: compare with matched group,
*P＜0.05; Compare with the Radix Puerariae group,
#P＜0.05; Compare with the Fructus Trichosanthis group,
﹠amp;P＜0.05.
Experimental result and conclusion: experimental result sees Table 2.
Compare with matched group, Radix Puerariae group, the ear arteriole of Fructus Trichosanthis group mice, venule caliber enlarge markedly (p＜0.05), and blood flow rate is significantly accelerated (p＜0.05); Ear arteriole, the venule caliber of each weight proportion group mice enlarge markedly (p＜0.05) in 125～2000 parts of Radix Puerariaes, 100～2000 parts of scopes of Fructus Trichosanthis, blood flow rate is significantly accelerated (p＜0.05), and all be better than single effect with Radix Puerariae or Fructus Trichosanthis, especially the better effects if of each weight proportion in 250～1000 parts of Radix Puerariaes, 500～1500 parts of scopes of Fructus Trichosanthis points out Radix Puerariae and Fructus Trichosanthis compatibility that the effect of collaborative microcirculation improvement is arranged.
Experimental example 3 pharmaceutical compositions of the present invention are to the research of experimental rat acute myocardial ischemia protective effect
Laboratory animal: the Wistar rat, 60, body weight is at 200～230g, male and female half and half.
Test sample: normal saline, commercial; The Radix Puerariae extract granule, self-control, 107mg is equivalent to crude drug 2.5g; The Fructus Trichosanthis extract granule, self-control, 570mg is equivalent to crude drug 7.5g; Medicament composition granule, self-control, 677mg contains Radix Puerariae extract 107mg (being equivalent to crude drug 2.5g), Fructus Trichosanthis extract 570mg (being equivalent to crude drug 7.5g).
Experimental technique: 60 of rats, be divided into 6 groups at random, 10 every group, be respectively the blank group, Radix Puerariae extract group, Fructus Trichosanthis extract group, pharmaceutical composition low dose group, dosage group in the pharmaceutical composition, pharmaceutical composition 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 3 pharmaceutical composition antagonism pituitrin (x ± s, n=10)
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01; Compare with the Radix Puerariae group,
#P＜0.05; Compare with the Fructus Trichosanthis group,
﹠amp;P＜0.05.
Experimental result and conclusion: experimental result sees Table 3.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 the T ripple in the 2min, recover gradually, but 5min does not return to normally thereupon; There are 8 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 the Fructus Trichosanthis 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 each dosage group ST section of pharmaceutical composition 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 Radix Puerariae extract group, Fructus Trichosanthis extract group, the effect that the anti-electrocardiogram of each dosage of pharmaceutical composition changes all is better than single effect (p＜0.05) with Radix Puerariae extract and Fructus Trichosanthis extract.Prompting Radix Puerariae extract and Fructus Trichosanthis extract drug combination have the collaborative effect that resists myocardial ischemia.
The antiplatelet aggregative activity of experimental example 4 pharmaceutical compositions of the present invention
Animal subject: the Wistar rat, body weight 200～230g, is divided into 6 groups at random by 60.
Test sample: the Radix Puerariae extract capsule, self-control, 107mg is equivalent to crude drug 2.5g;
The Fructus Trichosanthis extract capsule, self-control, 380mg is equivalent to crude drug 5g;
Composition capsule (Radix Puerariae extract+Fructus Trichosanthis extract), self-control, 487mg contains Radix Puerariae extract 107mg (being equivalent to crude drug 2.5g), Fructus Trichosanthis extract 380mg (being equivalent to crude drug 5g).
Experimental technique: rat is divided into 6 groups at random, 10 every group, is respectively normal saline matched group, Radix Puerariae extract Capsules group, Fructus Trichosanthis extract Capsules group, the high, medium and low dosage group of composition capsule.Each treated animal gastric infusion, once a day, successive administration 7 days, after the last administration 1 hour, from abdominal aortic blood, anticoagulant adopted 3.28% sodium citrate after the Animal Anesthesia, with blood with 1: 9 mixed.With anticoagulated whole blood 1500rmin under 20 ℃ of conditions
-1Centrifugal 5min obtains platelet rich plasma (PRP).After leaving and taking quantitative PRP, will remain PRP once more with 3000rmin
-1Centrifugal 10min obtains own control platelet poor plasma (PPP).Regulate PRP concentration with PPP, make each PRP concentration identical.In 37 ℃ constant temperature hole after the preheating, (final concentration is 3 μ molL to add ADP with PRP
-1) cause and write down maximum agglutination rate by platelet aggregation.
Table 4 pharmaceutical composition antiplatelet aggregative activity of the present invention (X ± S)
Annotate: compare with the normal saline matched group,
*P＜0.05,
*P＜0.01; Compare with the Radix Puerariae group,
#P＜0.05; Compare with the Fructus Trichosanthis group,
﹠amp;P＜0.05.
Experimental result: by last table experimental data as can be known,
1) compare with the normal saline matched group, Radix Puerariae extract Capsules group, Fructus Trichosanthis extract Capsules group platelet maximum agglutination rate all significantly reduce (p＜0.05), and the platelet maximum agglutination rate of each dosage group of composition capsule all extremely significantly reduces (p＜0.01).
2) compare with the Radix Puerariae extract Capsules group, the platelet maximum agglutination rate of the basic, normal, high dosage group of composition capsule all significantly reduces (p＜0.05).
3) compare with the Fructus Trichosanthis extract Capsules group, the platelet maximum agglutination rate of the basic, normal, high dosage group of composition capsule all significantly reduces (p＜0.05).
Conclusion: compare with the normal saline matched group, each administration group all can significantly reduce the platelet maximum agglutination rate of rat, showing all has anti thrombotic action, and wherein the composition capsule curative effect is better than singly using the Fructus Trichosanthis extract capsule with Radix Puerariae extract capsule and list, points out two medicine compatibilities that synergistic function is arranged.Each dosage group empirical value of composition capsule shows that along with the increase of dosage, the effect of anticoagulant is better, points out medicament composition capsule antiplatelet aggregative activity of the present invention to be dose-effect and increases progressively relation.
Experimental example 5 pharmaceutical compositions of the present invention are to the protective effect of rabbit cerebral ischemia perfusion injury
Animal subject: rabbit, 114, the male and female dual-purpose, body weight 2.3～2.7kg is divided at random: ischemia-reperfusion group (18), medicinal composition for injections group (18 of each dosage groups), injection Radix Puerariae extract group (18), injection Fructus Trichosanthis extract group (18) and Sham-operated control group (6).
Test sample: sodium chloride injection, commercial; The injection Radix Puerariae extract, self-control, 107mg is equivalent to crude drug 2.5g; The injection Fructus Trichosanthis extract, self-control, 174mg is equivalent to crude drug 5g; Medicinal composition for injections, self-control, 280mg contains Radix Puerariae extract 107mg (being equivalent to crude drug 2.5g), Fructus Trichosanthis extract 174mg (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 medicinal composition for injections dosage is followed successively by 230mg/kg, 250mg/kg, 270mg/kg, the dosage of Radix Puerariae, Fructus Trichosanthis group is 270mg/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) medicinal composition for injections 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 pharmaceutical composition group.(3) 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.(4) injection Fructus Trichosanthis 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 Fructus Trichosanthis 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 medicinal composition for injections
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 Radix Puerariae extract group and injection Fructus Trichosanthis 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 time point brain water content of each dosage group of medicinal composition for injections 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 Radix Puerariae extract group is compared remarkable reduction (p＜0.05) with each time point brain water content of injection Fructus Trichosanthis 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 medicinal composition for injections, injection Radix Puerariae extract group, injection Fructus Trichosanthis 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 medicinal composition for injections is more remarkable.
Conclusion: above-mentioned experimental result shows that behind the cerebral ischemia re-pouring, pharmaceutical composition, Radix Puerariae extract, Fructus Trichosanthis 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 pharmaceutical composition, Radix Puerariae extract, Fructus Trichosanthis 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 medicinal composition for injections drug effect in every index all is higher than the effect of injection Radix Puerariae extract and the independent medication of injection Fructus Trichosanthis 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.
In following examples in the preparation of each dosage form the preparation method of used Radix Puerariae extract, Fructus Trichosanthis extract see embodiment 1, embodiment 2 respectively, adjuvant can be replaced with acceptable accessories, perhaps reduces, increases.
The preparation and the assay of embodiment 1 Radix Puerariae extract
1, the preparation of Radix Puerariae extract
Get the Radix Puerariae medical material, pulverize, add 70% alcohol heating reflux and extract secondary, 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.
Prepare three batches of Radix Puerariae extracts respectively, yield sees Table 5.
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, thin up shakes up to scale. 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 5.
The assay result and the yield of table 5 Radix Puerariae extract
The preparation and the assay of embodiment 2 Fructus Trichosanthis extracts
The preparation one of Fructus Trichosanthis extract
Get the Fructus Trichosanthis medical material, oven dry is ground into coarse powder, add entry reflux, extract, secondary, add 10 times of water gagings at every turn, reflux, extract, 2 hours, filter, merging filtrate, being concentrated into relative density is the concentrated solution of 1.10～1.15 (60 ℃), add ethanol and reach 80% to containing the alcohol amount, placement is spent the night, and gets supernatant, reclaim ethanol to there not being the alcohol flavor, be decompressed to the thick paste shape, vacuum drying promptly gets Fructus Trichosanthis extract 1.
Prepare three batches of Fructus Trichosanthis extracts 1 respectively, yield sees Table 6.
The preparation two of Fructus Trichosanthis extract
Get the Fructus Trichosanthis medical material, oven dry is ground into coarse powder, add entry reflux, extract, secondary, add 10 times of water gagings at every turn, reflux, extract, 2 hours, filter, merging filtrate, being concentrated into relative density is the concentrated solution of 1.10～1.15 (60 ℃), add ethanol and reach 80% to containing the alcohol amount, placement is spent the night, and gets supernatant, reclaims ethanol to there not being the alcohol flavor, be decompressed to the thick paste shape, with after the suitable quantity of water dissolving, extract secondary with the jolting of equivalent petroleum ether behind the vacuum drying, water liquid extracts three times with the jolting of equivalent water-saturated n-butanol, merge n-butanol extracting liquid, be concentrated into driedly, residue adds low amounts of water makes dissolving, last macroporous resin column, the difference water, 15% ethanol, 70% ethanol elution, collect 70% ethanol elution, decompression recycling ethanol is concentrated into the thick paste shape, spray drying promptly gets Fructus Trichosanthis extract 2.
Prepare three batches of Fructus Trichosanthis extracts 2 respectively, yield sees Table 6.
The Fructus Trichosanthis extract assay
The assay of steroid compound
Standard curve preparation: get ginsenoside R
G1The about 2mg of reference substance through 60 ℃ of vacuum dryings 2 hours, accurately claims surely, puts in the 10ml measuring bottle, with anhydrous alcohol solution and be diluted to scale, shakes up.Accurately pipette respectively precision respectively and measure above-mentioned solution 5,10,30,50,70,90,110 μ L in the 25ml measuring bottle, thin up is settled to scale, shakes up, and makes series standard solution.All precision pipettes 0.2ml, places 10ml tool plug test tube, and water-bath volatilizes methanol, add 0.7ml8% vanillin glacial acetic acid solution, add people 5ml perchloric acid again, shake up, in 60 ℃ of water-bath 15min, take out at once and dash to room temperature with tap water, making blank to add the parallel sample of sample, measure absorbance in 560nm, is vertical coordinate with the absorbance, concentration is abscissa, the drawing standard curve.
Algoscopy: it is an amount of to get Fructus Trichosanthis extract, add an amount of ultrasonic solution that makes dissolving be mixed with 25ml of methanol, accurately pipette sample solution 0.2ml, place 10ml tool plug test tube, water-bath volatilizes methanol, add 0.5mL 8% vanillin glacial acetic acid solution, add people 5ml perchloric acid again, shake up, in 60 ℃ of water-bath 15min, take out at once and dash to room temperature, measure absorbance in 560nm with tap water.Read the content of steroid compound the need testing solution from standard curve, calculate, promptly.
Extract three batches of Fructus Trichosanthis extracts respectively by above two technologies, record according to above-mentioned content assaying method and the results are shown in Table 6.
The assay result and the yield of table 6 Fructus Trichosanthis extract
The preparation of embodiment 3 pharmaceutical composition tablets of the present invention
Prescription 1:
Radix Puerariae extract 21.4g (being equivalent to crude drug 500g)
Fructus Trichosanthis extract 1 76g (being equivalent to crude drug 1000g)
Starch 65g
Microcrystalline Cellulose 45g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 20g
Prepare 1000 altogether
Prescription 2:
Radix Puerariae extract 10.7g (being equivalent to crude drug 250g)
Fructus Trichosanthis extract 1 114g (being equivalent to crude drug 1500g)
Starch 65g
Microcrystalline Cellulose 45g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 20g
Prepare 1000 altogether
Prescription 3:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 1 30.4g (being equivalent to crude drug 400g)
Starch 65g
Microcrystalline Cellulose 45g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 20g
Prepare 1000 altogether
Prescription 4:
Radix Puerariae extract 4.25g (being equivalent to crude drug 100g)
Fructus Trichosanthis extract 1 122g (being equivalent to crude drug 1600g)
Starch 65g
Microcrystalline Cellulose 45g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 6g
Carboxymethylstach sodium 20g
Prepare 1000 altogether
Method for making:
It is standby that Radix Puerariae extract and Fructus Trichosanthis extract were pulverized 100 mesh sieves; Take by weighing various adjuvants according to recipe quantity; Hypromellose 2% the aqueous solution made soluble in water is standby; With Radix Puerariae extract, Fructus Trichosanthis extract, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material; Cross 20 mesh sieve system granules; Granule is dried under 60 ℃ condition; Dry good granule adds magnesium stearate and carboxymethylstach sodium, crosses 18 mesh sieve granulate, mix homogeneously; Sampling, the semi-finished product chemical examination; According to the definite sheet weight sheet of chemical examination; Finished product is examined entirely, the packing warehouse-in.The tablet that the present composition is made can administration in a day 1～5 time, one time 1～10.
The preparation of embodiment 4 medicament composition capsule agent of the present invention
Prescription 1:
Radix Puerariae extract 21.4g (being equivalent to crude drug 500g)
Fructus Trichosanthis extract 1 152g (being equivalent to crude drug 2000g)
Starch 50g
Microcrystalline Cellulose 5g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4g
Prepare 1000 altogether
Prescription 2:
Radix Puerariae extract 64g (being equivalent to crude drug 1500g)
Fructus Trichosanthis extract 1 113g (being equivalent to crude drug 1500g)
Starch 50g
Microcrystalline Cellulose 5g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4g
Prepare 1000 altogether
Prescription 3:
Radix Puerariae extract 21.4g (being equivalent to crude drug 500g)
Fructus Trichosanthis extract 1 76g (being equivalent to crude drug 1000g)
Starch 50g
Microcrystalline Cellulose 5g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4g
Prepare 1000 altogether
Prescription 4:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 1 7.5g (being equivalent to crude drug 100g)
Starch 50g
Microcrystalline Cellulose 5g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4g
Prepare 1000 altogether
Prescription 5:
Radix Puerariae extract 43g (being equivalent to crude drug 1000g)
Fructus Trichosanthis extract 1 114g (being equivalent to crude drug 1500g)
Starch 50g
Microcrystalline Cellulose 5g
The 2%HPMC aqueous solution is an amount of
Magnesium stearate 4g
Prepare 1000 altogether
Method for making:
It is standby that Radix Puerariae extract and Fructus Trichosanthis extract were pulverized 100 mesh sieves; Take by weighing adjuvant according to recipe quantity; Hypromellose 2% the aqueous solution made soluble in water is standby; With Radix Puerariae extract, Fructus Trichosanthis extract, starch, microcrystalline Cellulose mix homogeneously, adding 2%HPMC aqueous solution is an amount of, stirs, and makes suitable soft material; Cross 20 mesh sieve system granules; Granule is dried under 60 ℃ condition; Dry good granule adds magnesium stearate, crosses 18 mesh sieve granulate, mix homogeneously; Sampling, the semi-finished product chemical examination; The loading amount of determining according to chemical examination incapsulates; Finished product is examined entirely, the packing warehouse-in.The capsule that the present composition is made can administration in a day 1～5 time, one time 1～10.
The preparation of embodiment 5 medicament composition granule agent of the present invention
Prescription 1:
Radix Puerariae extract 107g (being equivalent to crude drug 2500g)
Fructus Trichosanthis extract 1 151g (being equivalent to crude drug 2000g)
Icing Sugar 1200g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription 2:
Radix Puerariae extract 21.4g (being equivalent to crude drug 500g)
Fructus Trichosanthis extract 1 76g (being equivalent to crude drug 1000g)
Icing Sugar 1200g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription 3:
Radix Puerariae extract 10.5g (being equivalent to crude drug 250g)
Fructus Trichosanthis extract 1 151g (being equivalent to crude drug 2000g)
Icing Sugar 1200g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription 4:
Radix Puerariae extract 69g (being equivalent to crude drug 1600g)
Fructus Trichosanthis extract 1 30g (being equivalent to crude drug 400g)
Icing Sugar 1200g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Prescription 5:
Radix Puerariae extract 8.5g (being equivalent to crude drug 200g)
Fructus Trichosanthis extract 1 182g (being equivalent to crude drug 2400g)
Icing Sugar 1200g
The 2%HPMC50% alcoholic solution is an amount of
Prepare 1000 bags altogether
Method for making:
It is standby that sucrose was pulverized 100 mesh sieves; It is standby that Radix Puerariae extract and Fructus Trichosanthis extract were pulverized 100 mesh sieves; Take by weighing adjuvant according to recipe quantity; With the method mix homogeneously that Radix Puerariae extract, Fructus Trichosanthis extract and Icing Sugar progressively increase with equivalent, adding 2%HPMC50% alcoholic solution is an amount of, stirs, and makes suitable soft material; Cross 20 mesh sieve system granules; Granule is dried under 60 ℃ condition; Dried granule is crossed 18 mesh sieve granulate; Sampling, the content of principal agent is determined loading amount in the semi-finished product chemical examination granule; Packing, finished product is examined entirely, the packing warehouse-in.The granule that the present composition is made can administration in a day 1～3 time, one time 1～2 bag.
The preparation of embodiment 6 drug composition oral liquid of the present invention
Prescription 1:
Radix Puerariae extract 21.4g (being equivalent to crude drug 500g)
Fructus Trichosanthis extract 1 76g (being equivalent to crude drug 1000g)
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Prescription 2:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 1 15g (being equivalent to crude drug 200g)
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Prescription 3:
Radix Puerariae extract 22g (being equivalent to crude drug 500g)
Fructus Trichosanthis extract 1 114g (being equivalent to crude drug 1500g)
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Prescription 4:
Radix Puerariae extract 64g (being equivalent to crude drug 1500g)
Fructus Trichosanthis extract 1 38g (being equivalent to crude drug 500g)
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Prescription 5:
Radix Puerariae extract 69g (being equivalent to crude drug 1600g)
Fructus Trichosanthis extract 1 31g (being equivalent to crude drug 400g)
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Prescription 6:
Radix Puerariae extract 128g (being equivalent to crude drug 3000g)
Fructus Trichosanthis extract 1 114g (being equivalent to crude drug 1500g)
Sodium benzoate 15g
Stevioside 10g
Water adds to 10000ml
Prepare 1000 altogether
Method for making:
Radix Puerariae extract and Fructus Trichosanthis extract is complete with the water dissolution of dosing amount 60%; Sodium benzoate and stevioside is complete with the water dissolution of dosing amount 20%; Merge above-mentioned two solution, mend and add water to full dose; Cross the filtering with microporous membrane of 0.8um; The semi-finished product chemical examination; Fill.Finished product is examined entirely, the packing warehouse-in.The oral liquid that the present composition is made can administration in a day 1～3 time, one time 1～2.
The preparation of embodiment 7 pharmaceutical composition aqueous injection of the present invention
Prescription 1:
Radix Puerariae extract 43g (being equivalent to crude drug 1000g)
Fructus Trichosanthis extract 2 69g (being equivalent to crude drug 2000g)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 2:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 2 7g (being equivalent to crude drug 200g)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 3:
Radix Puerariae extract 10.5g (being equivalent to crude drug 250g)
Fructus Trichosanthis extract 2 69g (being equivalent to crude drug 2000g)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 4:
Radix Puerariae extract 43g (being equivalent to crude drug 1000g)
Fructus Trichosanthis extract 2 104g (being equivalent to crude drug 3000g)
Water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 5:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 2 104g (being equivalent to crude drug 3000g)
Water for injection adds to 5000ml
Prepare 1000 altogether
Method for making:
Carry 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; Get the water for injection of dosing amount 80%, add Radix Puerariae extract and Fructus Trichosanthis extract, the heated and stirred dissolving fully; Benefit adds to the full amount of water for injection; The needle-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes; Through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution; Microporous filter membrane fine straining through 0.45um; Check the clarity of solution, the semi-finished product chemical examination; With the solution sealing by fusing in glass ampule; 100 ℃ of flowing steam sterilizations 30 minutes; While hot sample being put into 0.01% methylene blue solution hunts leak; Lamp inspection, finished product is examined entirely, the packing warehouse-in.The liquid drugs injection that the present composition is made can administration in a day 1～3 time, one time 1～2.
The preparation of embodiment 8 pharmaceutical composition injectable powder of the present invention
Prescription 1:
Radix Puerariae extract 43g (being equivalent to crude drug 1000g)
Fructus Trichosanthis extract 2 69g (being equivalent to crude drug 2000g)
Mannitol 300g
Sterile water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 2:
Radix Puerariae extract 107g (being equivalent to crude drug 2500g)
Fructus Trichosanthis extract 2 69g (being equivalent to crude drug 2000g)
Mannitol 300g
Sterile water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 3:
Radix Puerariae extract 8.5g (being equivalent to crude drug 200g)
Fructus Trichosanthis extract 2 110g (being equivalent to crude drug 3200g)
Mannitol 300g
Sterile water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 4:
Radix Puerariae extract 107g (being equivalent to crude drug 2500g)
Fructus Trichosanthis extract 2 103g (being equivalent to crude drug 2500g)
Mannitol 300g
Sterile water for injection adds to 5000ml
Prepare 1000 altogether
Prescription 5:
Radix Puerariae extract 22g (being equivalent to crude drug 500g)
Fructus Trichosanthis extract 2 69g (being equivalent to crude drug 2000g)
Mannitol 300g
Sterile water for injection adds to 5000ml
Prepare 1000 altogether
Method for making:
Vessel and antibiotic glass bottle that elder generation uses dosing, plugs etc. carry out aseptic process; Take by weighing supplementary material according to recipe quantity; Get the sterile water for injection of dosing amount 80%, Radix Puerariae extract and Fructus Trichosanthis extract are added, the heated and stirred dissolving fully.Add the dissolving of mannitol heated and stirred more fully, add sterile water for injection to full dose; The needle-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes; Through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution; Microporous filter membrane fine straining through 0.22um; Check the clarity of solution, the semi-finished product chemical examination; Be sub-packed in the antibiotic glass bottle half tamponade.Sample is put into the freeze dryer lyophilization.Pre-freeze-45 ℃ 5 hours, low-temperature vacuum drying-45 ℃～0 ℃ 20 hours was warming up to 25 ℃ of vacuum dryings 3 hours then; Lyophilizing finishes, and lid is rolled in tamponade; Finished product is examined entirely, the packing warehouse-in.The powder pin that the present composition is made can administration in a day 1～3 time, one time 1～2.
The preparation of embodiment 9 pharmaceutical composition sodium chloride injections of the present invention
Prescription 1:
Radix Puerariae extract 43g (being equivalent to crude drug 1000g)
Fructus Trichosanthis extract 2 69g (being equivalent to crude drug 2000g)
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 2:
Radix Puerariae extract 8.5g (being equivalent to crude drug 200g)
Fructus Trichosanthis extract 2 83g (being equivalent to crude drug 2400g)
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 3:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 2 3.5g (being equivalent to crude drug 100g)
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 4:
Radix Puerariae extract 69g (being equivalent to crude drug 1600g)
Fructus Trichosanthis extract 2 14g (being equivalent to crude drug 400g)
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 5:
Radix Puerariae extract 172g (being equivalent to crude drug 4000g)
Fructus Trichosanthis extract 2 69g (being equivalent to crude drug 2000g)
Sodium chloride 900g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Method for making:
Carry 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; The water for injection of getting dosing amount 20% adds the heated and stirred dissolving fully with Fructus Trichosanthis extract and Flos Carthami flavochrome.Sodium chloride is complete with the water for injection dissolving of dosing amount 40%; Merge two solution, benefit adds to the full amount of water for injection; The needle-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes; Through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution; Microporous filter membrane fine straining through 0.45um; Check the clarity of solution, the semi-finished product chemical examination; Fill is in the infusion bottle of 100ml; 115 ℃ of pressure sterilizings 30 minutes; Lamp inspection, finished product is examined entirely, the packing warehouse-in.The transfusion that the present composition is made can administration in a day 1～3 time, one time 1～2 bottle.
The preparation of embodiment 10 pharmaceutical composition glucose injections of the present invention
Prescription 1:
Radix Puerariae extract 43g (being equivalent to crude drug 1000g)
Fructus Trichosanthis extract 2 69g (being equivalent to crude drug 2000g)
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 2:
Radix Puerariae extract 17g (being equivalent to crude drug 400g)
Fructus Trichosanthis extract 2 83g (being equivalent to crude drug 2400g)
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 3:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 2 14g (being equivalent to crude drug 400g)
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 4:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 2 28g (being equivalent to crude drug 800g)
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Prescription 5:
Radix Puerariae extract 86g (being equivalent to crude drug 2000g)
Fructus Trichosanthis extract 2 52g (being equivalent to crude drug 1500g)
Glucose 5000g
Water for injection adds to 100000ml
Prepare 1000 bottles altogether
Method for making:
Carry 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, the water for injection of getting dosing amount 20% adds the heated and stirred dissolving fully with Fructus Trichosanthis extract and Flos Carthami flavochrome.Glucose is complete with the water for injection dissolving of dosing amount 40%; Merge two solution, benefit adds to the full amount of water for injection; The needle-use activated carbon that adds dosing amount 0.1%, heated and stirred 15 minutes; Through sand filtration rod filtering decarbonization.Measure the also pH value of regulator solution; Microporous filter membrane fine straining through 0.45um; Check the clarity of solution, the semi-finished product chemical examination; Fill is in the infusion bottle of 100ml; 115 ℃ of pressure sterilizings 30 minutes; Lamp inspection, finished product is examined entirely, the packing warehouse-in.The transfusion that the present composition is made can administration in a day 1～3 time, one time 1～2 bottle.
Claims (10)
1. a pharmaceutical composition that is used for cardiovascular and cerebrovascular disease is characterized in that, make composition and effectiveness crude drug consist of Radix Puerariae and Fructus Trichosanthis, its parts by weight are: 125～2000 parts of Radix Puerariaes, 100～2000 parts of Fructus Trichosanthis.
2. pharmaceutical composition as claimed in claim 1 is characterized in that, its parts by weight are: 250～1000 parts of Radix Puerariaes, 500～1500 parts of Fructus Trichosanthis.
3. pharmaceutical composition as claimed in claim 2 is characterized in that, its parts by weight are: 500 parts of Radix Puerariaes, 1000 parts of Fructus Trichosanthis.
4. as the described arbitrary preparation of drug combination method of claim 1～3, it is characterized in that, Radix Puerariae and Fructus Trichosanthis can obtain extract by singly carrying or mixing to obtain through refining fully with The suitable solvent and method, total extract is made arbitrary preparation with mixing acceptable accessories again, and the main effective ingredient of gained total extract is flavonoid and steroid compound.
5. pharmaceutical composition as claimed in claim 1, this pharmaceutical composition can also be made by Radix Puerariae extract and Fructus Trichosanthis extract, and its parts by weight are: 4～100 parts of Radix Puerariae extracts, 2～160 parts of Fructus Trichosanthis extracts.
6. pharmaceutical composition as claimed in claim 5 is characterized in that, its parts by weight are: 7.5～50 parts of Radix Puerariae extracts, 10～120 parts of Fructus Trichosanthis extracts.
7. pharmaceutical composition as claimed in claim 6 is characterized in that, its parts by weight are: 15～25 parts of Radix Puerariae extracts, 20～80 parts of Fructus Trichosanthis extracts.
8. as the described arbitrary pharmaceutical composition of claim 5～7, it is characterized in that content of total flavone is not less than 50% in the described Radix Puerariae extract, the content of steroid compound is not less than 10% in the Fructus Trichosanthis extract.
9. as 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.
10. pharmaceutical composition as claimed in claim 9 is characterized in that this pharmaceutical composition can be made injection or oral formulations.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2006100702796A CN101190254B (en) | 2006-11-24 | 2006-11-24 | Medicinal composition containing kudzu root or its extract and mongolian snakegourd or its extract |
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| CN2006100702796A CN101190254B (en) | 2006-11-24 | 2006-11-24 | Medicinal composition containing kudzu root or its extract and mongolian snakegourd or its extract |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1347709A (en) * | 2000-10-09 | 2002-05-08 | 王学勇 | Cardiac and cerebral vascular disease treating medicine |
| CN1583007A (en) * | 2004-06-02 | 2005-02-23 | 辽宁中医学院 | Chinese medicine for coronary heart disease |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1347709A (en) * | 2000-10-09 | 2002-05-08 | 王学勇 | Cardiac and cerebral vascular disease treating medicine |
| CN1583007A (en) * | 2004-06-02 | 2005-02-23 | 辽宁中医学院 | Chinese medicine for coronary heart disease |
Non-Patent Citations (2)
| Title |
|---|
| 张秀琴.治疗冠心病自拟验方二首.吉林中医药 6.1992,(6),29-30. |
| 张秀琴.治疗冠心病自拟验方二首.吉林中医药 6.1992,(6),29-30. * |
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