CN100384439C - Pharmaceutical composition for treating and/or preventing cardiovascular and cerebrovascular diseases and preparation method thereof - Google Patents

Abstract

The application discloses a traditional Chinese medicine composition for treating and/or preventing cardiovascular and cerebrovascular diseases, its preparation, especially the freeze-dried powder injection preparation, and their preparation method. The composition contains ginseng, astragalus root, ganoderma lucidum and leeches, and the weight ratio of each component is ginseng: astragalus root: ganoderma lucidum: leech=50-150:100-450:100-450:1-5. The pharmaceutical composition of the present invention can be made into various pharmaceutical preparations, including oral preparations or injections, and the injections are preferably freeze-dried powder preparations or aqueous injections. When the pharmaceutical composition of the present invention and its various preparations are used for the treatment and/or prevention of cardiovascular and cerebrovascular diseases such as cerebral arteriosclerosis, cerebral infarction, stroke, coronary atherosclerosis and coronary heart disease, angina pectoris, myocardial infarction, etc. Good curative and/or prophylactic effect.

Description

Pharmaceutical composition for treating and/or preventing cardiovascular and cerebrovascular diseases and preparation method thereof

technical field

The invention belongs to the technical field of traditional Chinese medicine. Specifically, the invention relates to a method for treating and/or preventing cerebral arteriosclerosis, cerebral infarction, stroke, coronary atherosclerosis and the coronary heart disease, angina pectoris, myocardial infarction and other cardiovascular and cerebrovascular diseases caused by them. Traditional Chinese medicine composition for disease, its preparation, especially freeze-dried powder preparation and oral liquid preparation, and their preparation method.

Background technique

Modern research proves that cerebral arteriosclerosis, cerebral infarction, coronary heart disease, angina pectoris, myocardial infarction, belong to cardiovascular and cerebrovascular diseases. It brings a huge economic burden and seriously affects the quality of life of middle-aged and elderly people.

At present, there are many medicines suitable for clinical diagnosis and treatment, such as: Compound Danshen Tablets, Xinnaokang, Dimailing Injection, etc., all have different therapeutic effects, but the curative effects are not ideal.

According to the theory and practice of traditional Chinese medicine, the active ingredients in ginseng are mainly ginsenosides. It is known that ginsenosides can reduce the lactic acid content of the brain and myocardium in mice under severe ischemia and hypoxia conditions, and have the ability to protect myocardial capillary endothelial cells and The role of reducing mitochondrial damage can protect the activity of superoxide dismutase in ischemic myocardium and reduce the content of myocardial lipid peroxide; ginsenosides can also reduce the occurrence of stroke in animals with acute cerebral ischemia. Astragalus has the effect of dilating blood vessels and expanding coronary arteries. It has a significant antagonism effect on cerebral hypoxia and can significantly prolong the survival time of mice. Ganoderma lucidum significantly reduces coronary resistance, increases coronary blood flow, protects ischemic myocardium, and has anti-platelet aggregation effects. Leech has a strong anticoagulant and fibrinolytic effect, has a significant inhibitory effect on platelet aggregation, and has a significant regression effect on atherosclerotic plaque.

According to the theory and principles of traditional Chinese medicine for treating and preventing cardiovascular and cerebrovascular diseases, the inventor selected the above-mentioned Chinese medicines for invigorating qi and promoting blood circulation, including ginseng, astragalus, ganoderma lucidum, and leech, to make a pharmaceutical composition for treating and/or preventing cardiovascular and cerebrovascular diseases. Obtained ideal therapeutic effect.

Contents of the invention

The purpose of the present invention is to provide a pharmaceutical composition for treating and/or preventing cardiovascular and cerebrovascular diseases, the composition contains ginseng, astragalus, ganoderma lucidum and leech, the ratio of parts by weight of each component is ginseng: astragalus: Ganoderma lucidum: Leech = 50-150: 100-450: 100-450: 1-5. The composition may also contain traditional Chinese medicine known to treat cardiovascular and cerebrovascular diseases, which has no adverse effect on the above four components, such as Danshen and the like. The ginseng in the composition can also be replaced by other ginseng such as red ginseng, which should contain a certain amount of ginsenoside.

More preferably, the ratio of parts by weight of each component is ginseng: astragalus: ganoderma: leech = 50-150: 100-300: 100-300: 1-2. More preferably, ginseng: astragalus: ganoderma lucidum: leech=100:300:300:1.5.

Another object of the present invention is to provide various pharmaceutical preparations made from the pharmaceutical composition of the present invention, such as oral preparations or injections, oral preparations such as oral liquids, tablets, granules and capsules. Injections such as aqueous solutions, suspensions, freeze-dried powder preparations, etc. The particularly preferred oral preparation of the present invention is oral liquid; the particularly preferred injection is aqueous injection or freeze-dried powder preparation, and the freeze-dried powder preparation can be used for intravenous injection or intravenous drip.

The pharmaceutical composition of the present invention and various preparations thereof have good effects in treating and/or preventing cardiovascular and cerebrovascular diseases, such as cerebral arteriosclerosis, cerebral infarction, coronary heart disease, angina pectoris, myocardial infarction and the like. The pharmaceutical composition and various preparations of the present invention have significant therapeutic effects on cardiovascular disease chest pain, chest tightness, palpitations, and shortness of breath caused by coronary heart disease, have obvious protective effects on acute myocardial ischemia-reperfusion injury, and can reduce myocardial infarction And/or the size of cerebral infarction, improving cerebral arteriosclerosis and cerebral insufficiency. Using the composition and various preparations in small doses for patients without obvious symptoms can obviously relieve symptoms, greatly reduce the possibility of acute attacks, and effectively improve the quality of life of patients.

Another object of the present invention is to provide a preparation method of the pharmaceutical composition of the present invention, the method comprising:

(1) Ginseng is extracted with 75% ethanol, concentrated for subsequent use;

(2) Decoct the ginseng residue in step (1) together with astragalus and ganoderma lucidum, extract with water, add 10% calcium hydroxide solution to the extract to adjust the pH to 12.0, and after standing for 1 hour, add sulfuric acid solution to adjust the pH to 5.0 , let stand for 4 hours, take the supernatant to concentrate, filter, and sterilize by autoclaving;

(3) decocting the leech with water to extract, concentrating the extract, diluting the concentrate with ethanol, filtering, concentrating, and removing ethanol;

(4) Mix the products of the above steps to obtain the pharmaceutical composition of the present invention.

The method for making the pharmaceutical composition of the present invention into various preparations can adopt various known preparation techniques in the field of pharmacy, various general equipment, and various conventional auxiliary raw materials such as carriers, diluents, excipients, etc. Finish.

For example, the products obtained by the above methods can be further processed into preparations suitable for various routes of administration. For example, the obtained above-mentioned composition is further prepared into oral liquid, tablet, granule and capsule by using conventional carriers and/or excipients according to conventional techniques in the field of pharmacy.

In the case of preparing an oral liquid, dilute the composition obtained by the above method with water, centrifuge to collect the supernatant, discard the precipitate, then filter with filter paper, add an appropriate amount of water to adjust the concentration, subpackage, and sterilize to obtain the oral liquid preparation; or appropriately reduce the concentration ratio of the extracts in steps 2 and 3, combine the products of steps (1), (2) and (3) and centrifuge, filter with filter paper, add appropriate amount of water to adjust the concentration, and pack , and sterilized to obtain an oral liquid preparation. or

Prepare injections according to conventional methods, for example, aqueous injections or freeze-dried powder injections. For example, in the case of preparing a freeze-dried powder preparation, water for injection can be added to the composition obtained by the above method, then filtered through a micromembrane, sub-packaged, and freeze-dried below -45°C to make a freeze-dried powder preparation . Before use, the freeze-dried powder preparation is diluted with an appropriate amount of 5% glucose or 0.9% sodium chloride solution, and can be used for intravenous injection or intravenous drip. In the case of preparing an aqueous injection, the composition of the present invention is diluted with water to a suitable concentration, bottled and sterilized to obtain the aqueous injection of the present invention.

The pyrogen, hemolysis, anaphylaxis and other tests of the injection of the present invention and the inspection results of various physical and chemical indicators meet the following regulations of the Chinese Pharmacopoeia 2000 edition injection.

The advantage of the preparation method of the present invention is that it can effectively extract and purify the effective active substances saponins and polysaccharides contained in the medicinal materials, especially in the case of freeze-dried powder injection preparations, the effective active substances are almost Unaltered, so that it can directly enter the blood through the vein to play a role.

More specifically, it can be prepared according to the following method:

1. Ginseng is crushed and extracted with 75% ethanol for 1-3 times, and the combined extracts are concentrated until there is no alcohol smell to obtain a concentrated solution (1);

2. Add 5-10 times the amount of water to the ginseng residue extracted in step 1 and the crushed astragalus and ganoderma lucidum, decoct and extract 1-3 times, combine the extracts, add 10% calcium hydroxide solution to it to adjust the pH 12.0, let it stand for 1 hour; add sulfuric acid solution to adjust to pH 5.0, let it stand for 4 hours; absorb the supernatant, concentrate it into a clear paste with a relative density of 1.00-1.05 (50°C), filter, and pot the filtrate in 500ml of saline bottle, sterilized by hot pressing at 115°C for 30 minutes, and left to stand for 14 days to obtain the extract (2);

3. Crush the leeches into powder, add 4-8 times the amount of water to decoct and extract 1-3 times, combine the extracts and concentrate them into a clear paste with a relative density of 1.00-1.05 (50°C), add ethanol until the alcohol content is 75 %, filter after standing for 24 hours, concentrate the filtrate, reclaim ethanol until the filtrate has no alcohol smell, and obtain the extract (3);

4. Mix the concentrated solution (1) with the extracts (2) and (3) to obtain the pharmaceutical composition of the present invention;

5. Add the above composition with water for injection to a certain volume, filter it through a micromembrane, divide it into vials, and freeze-dry it at -45°C or lower to obtain the freeze-dried powder preparation of the present invention; or

6. Dilute the composition of the present invention with water to a suitable concentration, dispense it into ampoules, and sterilize it to obtain the aqueous injection of the present invention.

7. Dilute the above composition with water, centrifuge to collect the supernatant, discard the precipitate, then filter with filter paper, add an appropriate amount of water to adjust the concentration, subpackage, and sterilize to obtain the oral liquid preparation of the present invention.

The toxicity test, drug efficacy test and clinical observation and treatment conducted by the inventors on the composition of the present invention and its preparations show that the medicine of the present invention is safe and reliable, and has stable curative effect.

Experiment 1 Acute Toxicology Study

Through this experiment, the acute toxic reaction produced after the composition of the present invention is administered to mice is observed, so as to provide reference for clinical medication.

Experimental Materials

Animals: Kunming mice, weighing 19-21 g (6-8 weeks old), half male and half male, provided by the Experimental Animal Laboratory of Shandong Provincial New Drug Pharmacological Research Center.

Experimental medication: the lyophilized powder preparation of Example 4 of the present invention, 0.3g/bottle, diluted with 0.9% sodium chloride injection to an appropriate concentration during the experiment.

Method and Results

Take 60 healthy mice, half male and half male, and randomly divide them into six groups. Prepare the liquid medicine according to the proportional dose and administer it through the tail vein. number. Results According to Sun's comprehensive method, the LD ₅₀ of Naoxinkang for injection was 15.18g/kg, and the 95% average credible limit was 15.18±2.01g/kg.

Experiment 2 Chronic Toxicity Study

Experimental Materials

Animals: Wistar rats, weighing 70-90 g, half male and half male, provided by the Experimental Animal Laboratory of Shandong Provincial New Drug Pharmacological Research Center.

Experimental medication: the lyophilized powder preparation of Example 4 of the present invention, 0.3g/bottle, diluted with 0.9% sodium chloride injection to an appropriate concentration during the experiment.

experimental method

Take 60 healthy Wistar rats, half male and half male, and randomly divide them into 4 groups, set 3.0, 1.5, 0.75g/kg, three dose administration groups with a volume of 10ml/kg, and give the administration volume 1ml/100g to the control group, etc. 0.9% Sodium Chloride Injection by Volume. Once a day, continuous administration for 90 days. The body weight was weighed every 10 days for 30 days, and the body weight was weighed once a month after 30 days. 24 hours after each administration, 10 rats in each group were killed by decapitation, and blood was collected for blood routine, liver and kidney function. The heart, liver, spleen, lung and kidney were dissected and fixed in 10% formalin solution, embedded in paraffin, sectioned, stained with hematoxylin and eosin, and observed under a microscope for histomorphological changes.

The results showed that the drug had no significant effect on the food intake, growth and growth, respiratory cycle, feces excretion, etc. of the tested animals during the experiment. Obvious difference, no toxicity was found, showing that the present invention is safe and reliable. The drug dose used in the test is equivalent to 25-100 times of the clinical dose calculated in kilograms of body weight.

The above results show that when the rats are injected with 25-100 times the clinical dosage, there is no obvious toxic and side effect, and once a day, 5 sticks (1.5g) of 5% glucose are added to the healthy normal people who are tested. Or in 300ml of 0.9% sodium chloride injection, the drip rate is 60 drops/1 minute, and the medicine is used continuously for one month. No obvious adverse reaction occurs, and the main organs and biochemical test indicators have no obvious changes. Clinical observation shows that after 1-2 courses of treatment, the patient has no obvious adverse reaction. Show that the drug is safe in clinical use.

Experiment 3 The protective effect of the composition of the present invention on myocardial ischemia-reperfusion injury.

The composition of the invention has obvious protective effect on acute myocardial ischemia-reperfusion injury in experimental dogs, and can reduce the size of myocardial infarction.

experimental method:

1. Select 20 healthy mongrel dogs, male or female, weighing 11-15Kg, and feed them for a week. They are randomly divided into four groups with 5 dogs in each group. They are respectively set up as a control group and observation groups with high, medium and low dosages. After the group was determined, each group was anesthetized with pentobarbital sodium 30 mg/kg intravenously, the thoracotomy was performed in the left fourth intercostal space, and the midpoint of the anterior descending branch of the left coronary artery or the root of the largest oblique branch was ligated, resulting in For acute myocardial infarction, 30 minutes after coronary artery ligation, each group was administered from the external jugular vein: the control group was given 0.9% sodium chloride injection per 2ml/kg, and the observation group was given: 80mg/kg, 40mg/kg, Three doses of 20 mg/kg, intravenous infusion at a speed of 60 drops per minute, and the test drug was the freeze-dried powder preparation of Example 4.

2. Data collection. The animals in each experimental group were intubated in the left common carotid artery and in the ventricle, and the pressure was converted into electrical signals through a transducer, and the blood pressure was recorded with an inductive recorder (Rm-6000 Nippon Denko). Left ventricle pressure and its first time derivative, the ascending aorta and the left circumflex coronary artery were separated, the flow transduction head was put on, the flow of the aorta and coronary artery was recorded with an electromagnetic flowmeter (MFV-1200 Nippon Denko), and the following data were collected: Item data, heart rate, left ventricular systolic pressure, maximum rate of increase in ventricular pressure, maximum rate of decrease in ventricular pressure, left ventricular end-diastolic pressure, aortic flow, stroke volume, coronary flow, etc.

3. Measurement of myocardial infarction area. After the experimental data collection, the animals were sacrificed, the heart was stained with nitrotetrazolium blue, and the myocardial infarction area was measured by weighing method.

The myocardial infarct size was calculated according to the following formula:

Myocardial weight in infarct area/left ventricle weight×100%

The results are shown in Table 2.

Experiment 4 The therapeutic effect of the composition of the present invention on myocardial ischemia

experimental method:

1. Select 25 healthy Wistar rats, both male and female, with a body weight of 220-300 g. After feeding for three days, they are randomly divided into 5 groups, 5 rats in each group. Set up C: sham operation control group, A: ischemia group, B: acute administration group (ischemia group A is administered after 60 minutes of myocardial ischemia, and the tail vein is injected with a dose of 80 mg/kg once), D: reperfusion group (ischemia for 40 minutes followed by 20 minutes of reperfusion), E: chronic administration group (the reperfusion group was administered at a dose of 20 mg/kg for three days). , test drug is the freeze-dried powder preparation of embodiment 4. After the grouping was determined, each group was anesthetized intravenously with pentobarbital sodium, underwent a thoracotomy under artificial respiration, and ligated the left anterior descending coronary artery to cause acute myocardial infarction. All animals were monitored by ECG, and blood was collected from the abdominal aorta at the end of the experiment. , Plasma stored at low temperature to be tested for t-PA and PAI activity, and cardiac specimens were used to calculate the extent of myocardial infarction.

2. Data collection, t-PA and PAI activities were determined by chromogenic substrates, and the kits were from the Molecular Genetics Laboratory of Shanghai Medical University. Plasma and coronary effluent t-PA activities were expressed in Iu/ml and miu/ml, respectively, and PAI activity units were expressed in Au/ml.

3. Determination of the area of myocardial infarction. After the experimental data collection, the animals were sacrificed, the heart was stained with nitrotetrazolium, and the area of myocardial infarction was measured by weighing method.

Calculated according to the following fraction:

Myocardial weight in infarct area/left ventricle weight×100%

The results showed that the significantly reduced activity of tissue-type plasminogen activator (t-PA) PA inhibitor (PAL) could be restored to the level before ischemia, the size of myocardial infarction was significantly reduced, and the number of drugs was significantly reduced early. . see picture 1.

Experiment 5 The therapeutic effect of the composition of the present invention on cerebral ischemia

experimental method:

1. Select 15 healthy mixed-breed dogs, both male and female, with a weight of 12-15kg. After feeding for one week, they are randomly divided into 3 groups, with 5 dogs in each group. . Test drug is the freeze-dried powder injection preparation of embodiment 4. After the group was determined, each group was anesthetized with pentobarbital sodium 30 mg/kg intravenously, and the femoral artery was intubated, and the arterial systolic pressure and diastolic pressure were recorded through the pressure transducer AP-621G carrier amplifier, and recorded Standard II lead ECG to measure heart rate. Separate the common carotid artery and external carotid artery pulse, ligate the external carotid artery to cause experimental cerebral ischemia, place the probe of an electromagnetic flowmeter with an appropriate inner diameter on the common carotid artery, and measure the blood flow of the internal carotid artery with an MF-27 electromagnetic flowmeter. as cerebral blood flow. Femoral artery blood flow was measured in the same way as peripheral blood flow, and it was stable for 10 minutes after operation. The above indicators were recorded by RM-6000 multi-pass physiological recorder as the data before medication.

2. Data collection

The control group was given 0.9% sodium chloride injection, and the observation group was given two doses of 60 mg/kg and 30 mg/kg, diluted with 0.8% sodium chloride injection, and intravenously injected through a multi-channel electronic pump. Changes in cerebral blood flow and peripheral blood flow were recorded repeatedly at 1, 5, 10, 20 and 30 minutes after administration, and cerebral vascular resistance and peripheral vascular resistance were calculated according to blood pressure.

The experimental results show that the cerebral blood flow and peripheral blood flow of the experimental dog can be significantly increased during cerebral ischemia, as shown in Table 3 and Table 4.

Clinical trials were carried out with the composition of the present invention. The basic method of the clinical trials is as follows: 300 patients with acute angina pectoris, myocardial infarction and cerebral infarction were clinically observed and treated, and 100 cases of the same disease were set up as a control study. According to the diagnostic criteria recommended by the Cardiovascular Disease Professional Group of the First National Internal Medicine Academic Conference in February 1980. TCM dialectical classification: Mild symptoms are mostly qi deficiency (or both qi and yin deficiency) blood stasis and phlegm turbidity type, severe cases are mostly qi deficiency (or qi and yin deficiency) blood stasis and phlegm heat type, and obvious qi and yin deficiency symptoms are common in the late stage of the disease . Therapeutic method: the observation group only used the freeze-dried powder preparation of the embodiment of the present invention 4, once a day, once a 1.5g (5 sticks) was added in 5% glucose or 0.9% sodium chloride injection 300ml, intravenously. The course of treatment is 1 month. The control group was treated with conventional anti-cardiovascular drugs.

The clinical observation results are as follows:

1. The total effective rate of the curative effect of the present invention on cardiovascular disease chest pain, chest tightness, palpitation and shortness of breath caused by coronary heart disease is 96%.

2. The curative effect on angina pectoris caused by coronary heart disease is as follows: mild marked rate is 56%, improvement rate is 38%, total effective rate is 94%; moderate marked rate is 42%, improvement rate is 34%, total effective rate is 82%; severe marked rate 35%, the improvement rate is 61%, and the total effective rate is 96%.

3. Curative effect on cerebral arteriosclerosis and cerebral infarction.

The present invention has a total effective rate of 93% for cerebral arteriosclerosis, insufficient cerebral blood supply and cerebral infarction.

4. Curative effect on myocardial infarction

The total effective rate of the curative effect of the present invention on myocardial infarction is 88%.

5. The change of blood rheology before and after the treatment of the present invention (see Table 1) shows that the blood plasma viscosity etc. of the patient are greatly improved after treatment.

Table 1 The present invention's influence on hemorheology

Before treatment After treatment t-value P value Plasma viscosity (mpa.s) 1.67±0.06 1.32±0.07 4.12 ＜0.01 Whole blood low shear viscosity (mpa.s) 8.67±0.05 6.67±0.03 1.17 ＜0.05

Fibrinogen (g/l) 3.05±1.17 2.42±0.89 3.89 ＜0.01 Hematocrit(%) 49.57±5.06 47.23±3.12 0.05 <0.05

P value: the judgment value of statistical result difference comparison.

T value: T test statistical result value.

The dosage when the composition of the present invention is used to treat cardiovascular and cerebrovascular diseases, taking the freeze-dried powder injection or water injection of Example 4 as an example, the preparation can be used for intravenous injection or intravenous infusion, and the dosage for adults It can be once a day, 2-5 sticks per day, with 15 days as a course of treatment. Generally, 1-2 courses of treatment are required or follow the doctor's advice. In the case of oral preparations, the dosage for adults can be twice a day, 1-2 vials per day, with 15 days as a course of treatment, generally requiring 1-2 courses of treatment or following the doctor's advice. When it is used to prevent cardiovascular and cerebrovascular diseases, its dosage should be reduced appropriately, and oral preparations are preferred for preventive medication, and its dosage can be halved compared with the therapeutic dosage.

Description of drawings

Fig. 1 illustrates the effect of the composition of the present invention on the activity of t-PA (tissue plasminogen active substance, unit IU/ml), PAI (PA inhibitor, unit AU/ml) in mouse AMI (myocardial infarction) plasma Influence. Each test group is respectively: C, control group, A, ischemia group, B, acute administration group, D, reperfusion group, and E, chronic administration group. The symbols △△ and ** are difference comparison marks.

As can be seen from this figure, the mice that have administered the composition of the present invention, the tissue type plasminogen activator (t-PA) and the activity of PA inhibitor (PAL) that obviously reduces after its myocardial ischemia can recover to Before ischemic level, the size of myocardial infarction was significantly reduced, and the number of drugs showed a significant early time.

Detailed ways

In order to further illustrate the products and methods involved in the technology of the present invention, the following examples are given. However, these examples do not limit the scope of the present invention in any way.

Embodiment 1 The preparation of composition 1 of the present invention

Raw materials: ginseng 500g, astragalus 1000g, ganoderma lucidum 1000g, leeches 10g

Preparation:

1. Ginseng is crushed into pieces not larger than about 1.5 cm in particle size, added with 5 times the amount of 75% ethanol, heated and refluxed for extraction twice, each time for 4 hours, combined extracts, filtered, concentrated and recovered ethanol, to obtain a concentrated solution (1 )spare;

2. Crush astragalus and ganoderma into pieces with a diameter of about 1.5 cm, combine them with the ginseng dregs from step 1, add 10 times the amount of water to decoct three times, each time for 1.5 hours, combine the decoctions, and add 10% calcium hydroxide solution Adjust the pH value to 12.0 and let it stand for 1 hour; add sulfuric acid solution to adjust the pH value to 5.0 and let it stand for 4 hours; absorb the supernatant, concentrate to a clear paste with a relative density of 1.00-1.05 (50°C), filter, and press the filtrate Sterilize for 30 minutes, let stand for 14 days, obtain extract (2);

3. Grind the leech into fine powder, add 6 times the amount of water to decoct three times, 1 hour each time, combine the decoction, concentrate to a clear paste with a relative density of 1.00-1.05 (50°C), add ethanol to the alcohol content reach 75%, stand still for 24 hours, filter, concentrate the filtrate, recover ethanol until there is no alcohol smell, and obtain the extract (3);

4. Combine the above concentrate (1) and extracts (2) and (3) to obtain the pharmaceutical composition 1 of the present invention, 115 g in total.

Embodiment 2 The preparation of composition 2 of the present invention

According to the same method as Example 8, except that the amount of raw materials is: ginseng 1500g, astragalus 4500g, ganoderma lucidum 4500g, and leech 12g, the composition 2 of the present invention was prepared, a total of 450g.

Embodiment 3 The preparation of composition 3 of the present invention

According to the same method as in Example 8, except that the amount of raw materials is: 1000g of ginseng, 3000g of astragalus, 3000g of ganoderma lucidum, and 15g of leeches, the composition 3 of the present invention was prepared, totaling 300g.

Example 4 Preparation of freeze-dried powder preparation

The composition obtained in Example 3 was added with water for injection to 2000ml, divided into 1000 7ml control bottles, and freeze-dried at -45°C to obtain 1000 freeze-dried powder preparations of the present invention, each 0.3g Pack.

The preparation of embodiment 5 water injection

Add water for injection to 10,000ml of the composition obtained in Example 3, pack in 1000 10ml ampoules, and sterilize at 110°C for 30 minutes to obtain 1000 water injections of the present invention, each 10ml .

The preparation of embodiment 6 oral liquid

Raw materials: ginseng 500g, astragalus 1000g, ganoderma lucidum 1000g, leech 10g

Preparation:

1. Slice the ginseng, add 5 times the amount of 75% ethanol, heat and reflux for extraction twice, each time for 4 hours, combine the extracts, filter, concentrate and recover the ethanol, and obtain the concentrated solution (1) for later use;

2. Crush astragalus and ganoderma into pieces with a diameter of about 1.5 cm, combine them with the ginseng dregs from step 1, add 10 times the amount of water to decoct three times, each time for 1.5 hours, combine the decoctions, and add 10% calcium hydroxide solution Adjust the pH value to 12.0, and let it stand for 1 hour; add sulfuric acid solution to adjust the pH value to 5.0, and let it stand for 4 hours; absorb the supernatant, sterilize it by autoclaving for 30 minutes, and let it stand for 14 days to obtain the extract (2);

3. Grind the leech into fine powder, add 6 times the amount of water to decoct three times, 1 hour each time, combine the decoction, concentrate to a clear paste with a relative density of 1.00-1.05 (50°C), add ethanol to the alcohol content reach 75%, stand still for 24 hours, filter, concentrate the filtrate, recover ethanol until there is no alcohol smell, and obtain the extract (3);

4. Combine the above-mentioned concentrated solution (1) and extracts (2) and (3), centrifuge with a 4000 rpm centrifuge to obtain a supernatant, and discard the precipitate.

3. Filter the above supernatant with filter paper pulp, dilute to 2000ml, divide into 100 pre-treated 10ml oral liquid bottles, and sterilize by hot pressing at 110°C for 30 minutes, each containing 20ml.

The oral formulation of the composition of the present invention can also be obtained by diluting the composition obtained in Example 1.

The characteristics and beneficial effects of the method of the present invention compared with the prior art have been fully illustrated through the above description and the description of specific embodiments. Those skilled in the art can make various modifications and changes to the embodiments of the present invention according to the teachings of the present invention, especially with reference to the specific embodiments of the present invention without departing from the essence of the present invention. within the scope of protection of the invention.

Claims (10)

1. treat and/or prevent the pharmaceutical composition of cardiovascular and cerebrovascular disease, said composition is made up of Radix Ginseng, the Radix Astragali, Ganoderma and Hirudo, and the ratio of the parts by weight of described each component is a Radix Ginseng: the Radix Astragali: Ganoderma: Hirudo=50-150: 100-450: 100-450: 1-5.

2. according to the pharmaceutical composition of claim 1, the ratio of the parts by weight of wherein said each component is a Radix Ginseng: the Radix Astragali: Ganoderma: Hirudo=50-150: 100-300: 100-300: 1-2.

3. according to the pharmaceutical composition of claim 1 or 2, wherein said compositions is made into oral formulations or injection.

4. according to the pharmaceutical composition of claim 3, wherein said injection is freeze-dried powder or aqueous injection.

5. according to the pharmaceutical composition of claim 4, wherein said freeze-dried powder is used for intravenous injection or intravenous drip.

6. according to the pharmaceutical composition of claim 3, wherein said oral formulations is an oral liquid.

7. any one the preparation of drug combination method of claim 1-6, this method comprises:

(1) Radix Ginseng is used 75% ethanol extraction, it is standby to concentrate the back;

(2) with the Radix Ginseng residue of step (1) with the Radix Astragali, Ganoderma, use water boiling and extraction, extracting solution adds 10% aqua calcis and transfers to pH 12.0, after leaving standstill 1 hour, add sulfuric acid solution pH is transferred to 5.0, left standstill 4 hours, get supernatant concentration, filter, and pressure sterilizing;

(3) Hirudo is used water boiling and extraction, concentrated extracting solution with the concentrated solution ethanol dilution, filters and concentrates;

(4) product with above each step mixes, and obtains pharmaceutical composition of the present invention.

8. according to the preparation method of claim 7, wherein resulting pharmaceutical composition is further made and be suitable for oral preparation.

9. according to the preparation method of claim 7, in resulting pharmaceutical composition, add water for injection, make aqueous injection through packing.

10. according to the preparation method of claim 7, add water for injection in resulting pharmaceutical composition, filter through mocromembrane, packing in lyophilizing below-45 ℃, is made freeze-dried powder.

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