CN1320890C - Ginkgo medicine composition, its preparing method and its use - Google Patents

Abstract

The present invention relates to a gingko medical composition which contains ligustrazine (C8H12N2. H3PO4. H2O), ginkgo biloba extracts extracted from ginkgo leaf (measured by gingko total flavonoids). The weight of the ligustrazine in the medical composition is from 1 to 100 times than that of the ginkgo biloba extracts (measured by gingko total flavonoids). The present invention also discloses a method for preparing the medical composition. The medical composition of the present invention is a compound preparation which is composed of the ligustrazine and the ginkgo biloba extracts, the mutually replenishing and synergistic effects of the ligustrazine and the ginkgo biloba extracts are acted on a body, so that the functions of promoting blood circulation to remove blood stasis, preventing antiplatelet from aggregating, expanding blood vessels and improving microcirculatory can be sufficiently performed, and the present invention can be used for preparing medicine for treating ischemic cardio-cerebrovascular disease.

Description

A ginkgo medicinal composition, its preparation method and its use

technical field

The present invention relates to a kind of pharmaceutical composition, its preparation method and application thereof, specifically, relate to a kind of pharmaceutical composition composed of ligustrazine phosphate and ginkgo leaf extract extracted from ginkgo biloba, its preparation method and Its application in the preparation of medicines for treating ischemic cardiovascular and cerebrovascular diseases.

Background technique

Ginkgo biloba extract contains active ingredients such as total flavonoids and total lactones, and total flavonoids are the main active ingredients of Ginkgo biloba extract. The content of total flavonoids in Ginkgo biloba leaves is 0.5% to 1% (W/W), mainly in the form of glycosides, and the main aglycones are quercetin, kaempferol and isorhamnetin. Ginkgo biloba total flavonoids contained in Ginkgo biloba extract can expand coronary vessels, cerebral blood vessels, promote blood circulation and remove blood stasis, and improve symptoms and memory functions caused by cerebral ischemia. Ginkgo biloba extract can improve cerebral circulation, glucose metabolism and respiration in patients with cerebral thrombosis, and has a therapeutic effect on functional central nervous system damage. Ginkgo biloba extract is often used clinically for ischemic cardiovascular and cerebrovascular diseases, angina pectoris, cerebral embolism, cerebral vasospasm, etc.

Ligustrazine phosphate is 2,3,5,6-tetramethylpyrazine phosphate monohydrate (C ₈ H ₁₂ N ₂ H ₃ PO ₄ H ₂ O), white or off-white crystalline powder, with Anti-platelet aggregation, and depolymerizes the aggregated platelets, dilates small arteries, improves microcirculation, increases cerebral blood flow, and promotes blood circulation and removes blood stasis. Ligustrazine phosphate is rapidly absorbed and excreted, and can pass through the blood-cerebrospinal fluid barrier. Clinically used for ischemic cerebrovascular diseases (such as cerebral insufficiency, cerebral thrombosis, cerebral embolism).

99100263.6 discloses a pharmaceutical composition for treating cerebrovascular diseases. The pharmaceutical composition contains 15-30% of Ligustrazine hydrochloride, 40-60% of Panax notoginseng saponins, and 15-40% of Ginkgo biloba extract. The pharmaceutical composition has been proved by pharmacological and toxicological experiments to be a mild and long-lasting drug, which can enhance stress resistance and endurance, effectively prevent the formation of thrombus, promote meningeal microcirculation, increase blood flow, and prevent and treat local cerebral ischemia. Improve motor behavior.

However, at present, there is no report on the combination of ginkgo biloba extract and ligustrazine phosphate in a certain ratio to make medicine for clinical use.

Contents of the invention

The object of the present invention is to provide a ginkgo pharmaceutical composition, which is a compound preparation composed of ginkgo leaf extract and ligustrazine phosphate in a specific ratio.

Another object of the present invention is to provide a preparation method of ginkgo medicinal composition.

Another object of the present invention is to provide a preparation for treating ischemic cardiovascular and cerebrovascular diseases, such as cerebral insufficiency, cerebral thrombosis, cerebral embolism, cerebral vasospasm, cerebral insufficiency, senile dementia, Parkinson's syndrome, Application of drugs for stroke, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, angina pectoris, myocardial infarction.

Another object of the present invention is to provide an application in the preparation of medicines for treating liver fibrosis, microcirculation lesions caused by diabetes, and vasculitis.

The ginkgo pharmaceutical composition of the present invention contains ligustrazine phosphate (C ₈ H ₁₂ N ₂ ·H ₃ PO ₄ ·H ₂ O) and ginkgo leaf extract (calculated as total ginkgo flavonoids) extracted from ginkgo leaves. The weight of ligustrazine phosphate contained in the medicine is 1 to 100 times of the weight of ginkgo leaf extract (calculated as total flavonoids of ginkgo).

Furthermore, the weight of ligustrazine phosphate in the ginkgo pharmaceutical composition of the present invention is preferably 5-50 times, more preferably 5-20 times, and most preferably 10 times the weight of ginkgo leaf extract (calculated as total ginkgo flavonoids).

The parts by weight in the present invention may be μg, mg, g, kg and other well-known content units in the field of medicine.

The ginkgo pharmaceutical composition of the present invention can be prepared into various pharmaceutically available dosage forms, so the composition can also contain one or more adjuvants; such as sodium chloride, starch, talcum powder and stearin Magnesium acid, etc., are acceptable adjuvants in the field of pharmacy.

The ligustrazine phosphate described in the present invention can use raw materials that meet pharmaceutical standards.

The ginkgo leaf extract is prepared by extracting the dried leaves of Ginkgo biloba plant.

The preparation method of the ginkgo medicinal composition of the present invention is as follows: first extract the ginkgo leaves, extract the ginkgo leaves with ethanol reflux, concentrate and filter the extract, adsorb to the resin, elute, then concentrate and dry to obtain the ginkgo leaf extract, and then The ginkgo biloba extract is mixed with ligustrazine phosphate, and then pharmaceutically acceptable adjuvants are added to prepare pharmaceutically acceptable compositions in various dosage forms.

Specifically, the preparation process of Ginkgo biloba extract is:

After the Ginkgo biloba leaves are crushed, add 8 to 12 times the amount of 60 to 75% ethanol, reflux and extract twice at 40 to 50°C for 2 to 5 hours each time, combine the extracts, filter, and concentrate under reduced pressure to 1/8 to 1/8 of the volume of the extract. 1/12, add 1 to 2 times the amount of concentrated liquid water, and then filter with a filter aid with an added amount of 1 to 2% concentrated liquid, the filtrate is adsorbed by a macroporous resin, and desorbed with 60 to 75% ethanol solution. The solution was concentrated to dryness under reduced pressure to obtain the ginkgo biloba extract containing total flavonoids for future use.

The preparation process is preferably as follows: after the Ginkgo biloba leaves are crushed, add 8 to 12 times the amount of 70% ethanol, reflux and extract twice at 50° C. for 2 to 4 hours each time, combine the extracts, filter, and concentrate under reduced pressure to 1/2 the volume of the extract. 8 to 1/10, add 1 times the amount of concentrated liquid water, and then filter with filter aid with an added amount of 1% concentrated liquid, the filtrate is absorbed by macroporous resin, and desorbed with 70% ethanol solution, and the desorbed liquid is concentrated under reduced pressure To dry, the ginkgo biloba extract containing total flavonoids must be used for subsequent use.

The filter aid can be sodium zeolite or talcum powder.

The macroporous resin can be D101 type resin or HP-20 type resin.

During desorption, the amount of ethanol solution used is 2 to 3 times that of the adsorption resin.

Certainly, in the preparation process of the ginkgo medicinal composition of the present invention, the commercially available ginkgo leaf extract meeting the national drug standard can also be directly used.

The ginkgo medicinal composition of the present invention can be prepared into various pharmaceutically available dosage forms, such as freeze-dried powder injection, tablet, capsule, small-volume injection, large-volume injection, and the preferred dosage form is small-volume injection, large-volume injection, etc. volume injection. Various dosage forms of the ginkgo medicinal composition of the present invention can be prepared according to conventional production methods in the field of pharmacy. For example, ligustrazine phosphate and ginkgo biloba extract are mixed with one or more carriers, and then made into required dosage forms.

When the ginkgo medicinal composition of the present invention is prepared into a large-volume injection, an appropriate amount of sodium chloride needs to be added as an isotonic regulator.

The researchers of the present invention have conducted a large number of experiments and found that when the weight of ligustrazine phosphate (C ₈ H ₁₂ N ₂ ·H ₃ PO ₄ ·H ₂ O) in the ginkgo pharmaceutical composition is When the ratio is 10 times, the synergistic effect is the best and the curative effect is the best.

The most preferred ginkgo medicinal composition of the present invention has a large-capacity injection with a specification of 250ml/bottle, and each bottle contains ligustrazine phosphate (C ₈ H ₁₂ N ₂ H ₃ PO ₄ H ₂ O) 100mg, Ginkgo biloba extract (with Ginkgo biloba Total flavonoids) 10mg.

The usage is as follows: intravenous infusion, one bottle at a time, 10-15 days as a course of treatment.

The ginkgo medicinal composition of the present invention can achieve unexpected effects through the mutual complementation and synergistic effect of the ginkgo leaf extract and ligustrazine phosphate. The ginkgo leaf extract of the present invention contains active ingredients such as total ginkgo flavonoids, total ginkgo lactones and the like. Ginkgo total flavonoids have obvious effects of lowering blood fat and cholesterol, increasing coronary blood volume, reducing myocardial oxygen consumption, improving microcirculation, improving symptoms of cerebral ischemia and memory function, and improving cerebral circulation, glucose metabolism, Breathing is improved, and it has a therapeutic effect on functional central nervous system damage. Ginkgolide has anticoagulant effect, reduces blood viscosity, improves blood flow characteristics, prevents thrombus formation, and promotes thrombus dissolution. Ligustrazine Phosphate has the effect of anti-platelet aggregation, depolymerization of aggregated platelets, expansion of arterioles, improvement of microcirculation, increase of cerebral blood flow and promoting blood circulation and removing stasis. Ligustrazine phosphate is rapidly absorbed and excreted, and can play its role through the blood-cerebrospinal fluid barrier.

The ginkgo medicinal composition of the present invention is a compound preparation prepared by combining ginkgo leaf extract and ligustrazine phosphate in a specific ratio, which can be absorbed and excreted quickly and can pass through the blood-cerebrospinal fluid barrier. Through the mutual complementation and synergistic effect of the two on the body, it can fully promote blood circulation and remove blood stasis, have anti-platelet aggregation, dilate blood vessels, and improve microcirculation. It is suitable for the treatment of ischemic cardiovascular and cerebrovascular diseases, such as insufficient cerebral blood supply and cerebral thrombosis. , cerebral embolism, cerebral vasospasm, cerebral insufficiency, senile dementia, Parkinson's syndrome, stroke, hypertension, hyperlipidemia, arteriosclerosis, coronary heart pain, angina pectoris, myocardial infarction. It can also be used for liver fibrosis, microcirculation lesions caused by diabetes, and vasculitis.

Detailed ways

The present invention is further described with examples below, which is conducive to a better understanding of the present invention and its advantages and effects, but said examples are only used to illustrate the present invention rather than limit the present invention.

Example 1

After 5000g of ginkgo leaves are crushed, add 12 times the amount of 70% ethanol, and extract twice at 50°C under reflux for 3 hours each time, combine the extracts, filter, concentrate under reduced pressure to 1/10 of the volume of the extract, and add an equal amount of concentrated solution of water , adding 1% concentrated liquid amount of sodium zeolite filter aid to filter, the filtrate is adsorbed with D101 type macroporous resin, then desorbed with 70% ethanol solution of 2 times the amount of macroporous resin, and the desorbed solution is concentrated to dryness under reduced pressure to obtain 150g containing The ginkgo leaf extract of total flavonoids (containing 25% of total flavonoids) is ready for use.

Weigh 16g of Ginkgo biloba extract (containing 4g of total flavonoids), 40g of ligustrazine phosphate (C ₈ H ₁₂ N ₂ H ₃ PO ₄ H ₂ O), which can be made into 100,000ml liquid medicine, and finally made into a large-volume injection of 400 bottle (the specification is 250ml/bottle). Add an appropriate amount of water for injection at 85°C to the concentrated preparation tank, put 900g of sodium chloride into the concentrated preparation tank, stir fully to dissolve completely, add activated carbon according to 0.04% of the total volume of the preparation, heat at 90°C, keep it warm for 20 minutes, and cool down to 50 ℃, decarbonize and filter the medicinal solution into the dilute tank, add ligustrazine phosphate and ginkgo leaf extract into the dilute tank, stir well to dissolve completely, add activated carbon according to 0.02% of the total volume of the preparation, and let it stand for 20 minutes. Add water for injection to the volume of the solution, adjust the pH to 4.8±0.2, decarbonize and filter the drug solution, filter the drug solution at the terminal, fill it in an infusion bottle, fill it with nitrogen one by one, and sterilize it to obtain Infusion products.

Example 2

After crushing 5000g of ginkgo leaves, add 10 times the amount of 65% ethanol, and extract twice at 45°C under reflux for 4 hours each time, combine the extracts, filter, concentrate under reduced pressure to 1/8 of the volume of the extract, and add 1.5 times the amount of concentrated solution water, add 2% concentrated liquid amount of talcum powder filter aid to filter, the filtrate is adsorbed with macroporous resin (such as HP-20 type resin), desorbed with 72% ethanol solution of 3 times the amount of macroporous resin, and the desorbed solution is concentrated under reduced pressure To dry, get the ginkgo leaf extract that 150g contains total flavonoids (containing total flavonoids 25%) for subsequent use.

Weigh 8 g of ginkgo biloba extract (containing 2 g of total flavonoids), 50 g of ligustrazine phosphate (C ₈ H ₁₂ N ₂ H ₃ PO ₄ H ₂ O), which can be made into 2000ml liquid medicine, and finally made into a small volume injection of 1000ml branch. Add an appropriate amount of water for injection at 48°C in the preparation tank, then add ligustrazine phosphate and ginkgo leaf extract, stir well to dissolve completely, add activated carbon according to 0.02% of the total volume of preparation, let it stand for 20 minutes, add water for injection until the liquid is prepared Adjust the pH to 4.5, decarbonize and filter the medicinal solution, and then filter the medicinal solution at the terminal, and fill it into ampoules. During filling, the ampoules are filled with nitrogen one by one and sterilized to obtain a small-volume injection.

Example 3

After crushing 5000g of ginkgo leaves, add 10 times the amount of 70% ethanol, and extract twice at 50°C under reflux for 3 hours each time, combine the extracts, filter, concentrate under reduced pressure to 1/9 of the volume of the extract, add 2 times the amount of concentrated water , add the talcum powder filter aid of 1.5% concentrated liquid amount to filter, the filtrate is adsorbed with macroporous resin (such as D101 type resin), desorbs with the 70% ethanol solution of 2 times the amount of macroporous resin, desorbs and concentrates to dryness under reduced pressure, Obtain 150g of Ginkgo biloba extract containing total flavonoids (containing 25% of total flavonoids) for subsequent use.

Weigh 8 g of ginkgo biloba extract (containing 2 g of total flavonoids), 200 g of ligustrazine phosphate (C ₈ H ₁₂ N ₂ H ₃ PO ₄ H ₂ O), which can be made into 1000ml liquid medicine, and finally made into a small volume injection of 1000ml branch. Add an appropriate amount of water for injection at 48±2°C to the preparation tank, then add ligustrazine phosphate and ginkgo leaf extract, stir well to dissolve completely, add dextran 40 excipient, add activated carbon according to 0.02% of the total volume of the preparation, and let stand After 20 minutes, add water for injection to the dosing volume, adjust the pH to 4.8, decarbonize and filter the medicinal solution, and then filter the medicinal solution through the terminal, fill the medicinal solution after the terminal filtration (filling volume 1.0ml/bottle), and half stopper Then freeze-dry to make a freeze-dried powder product.

Example 4

After 5000g of ginkgo leaves are crushed, add 12 times the amount of 70% ethanol, and extract twice at 50°C under reflux for 3 hours each time, combine the extracts, filter, concentrate under reduced pressure to 1/8 of the volume of the extract, and add an equal amount of concentrated solution of water , adding 1% concentrated liquid amount of sodium zeolite filter aid to filter, the filtrate is adsorbed with D101 type macroporous resin, then desorbed with 70% ethanol solution of 3 times the amount of macroporous resin, and the desorbed solution is concentrated to dryness under reduced pressure to obtain 150g containing The ginkgo leaf extract of total flavonoids (containing 25% of total flavonoids) is ready for use.

Weigh 8 g of ginkgo biloba extract (containing 2 g of total flavonoids), 100 g of ligustrazine phosphate (C ₈ H ₁₂ N ₂ ·H ₃ PO ₄ ·H ₂ O), and finally make 1000 tablets. Mix ginkgo leaf extract, ligustrazine phosphate and 80 grams of starch, granulate with starch slurry, pass through a 20-mesh sieve for granulation, dry, add 1 gram of magnesium stearate, and press into tablets to obtain ginkgo pharmaceutical composition tablets agent.

Example 5

After crushing 5000g of ginkgo leaves, add 12 times the amount of 60% ethanol, and extract twice at 50°C under reflux for 2 hours each time. water, add 1% of the concentrated solution of sodium zeolite filter aid to filter, the filtrate is absorbed by D101 type macroporous resin, and then desorbed with 65% ethanol solution of 3 times the amount of macroporous resin, and the desorbed solution is concentrated to dryness under reduced pressure to obtain 150g The ginkgo biloba extract containing total flavonoids (containing 25% of total flavonoids) is ready for use.

Weigh 8 g of ginkgo leaf extract (containing 2 g of total flavonoids) and 2 g of ligustrazine phosphate (C ₈ H ₁₂ N ₂ ·H ₃ PO ₄ ·H ₂ O), which can be finally made into capsules. After mixing the ginkgo leaf extract, ligustrazine phosphate, 80 grams of starch and 80 grams of talcum powder, passing through a 100-mesh sieve, and packing into capsules, the ginkgo medicinal composition capsule is obtained.

Example 6

The extraction process of Ginkgo biloba extract is the same as that in Example 1, except that 16 g of Ginkgo biloba extract (containing 4 g of total flavonoids) and 20 g of ligustrazine phosphate (C ₈ H ₁₂ N ₂ ·H ₃ PO ₄ ·H ₂ O) are used.

Experimental example 1

This experimental example is the most preferred ginkgo pharmaceutical composition large volume injection of the present invention (each bottle contains ligustrazine phosphate (C ₈ H ₁₂ N ₂ H ₃ PO ₄ H ₂ O) 100mg, ginkgo leaf extract (in total Flavonoid meter) 10mg, 2.25g sodium chloride) appearance properties, pH value, heavy metals and other prescribed injection inspection items.

√Properties This product is a light yellow to light yellow clear liquid.

√pH value The pH value should be 3.5-5.5 (Appendix VI of Part Two of the Chinese Pharmacopoeia 2000 Edition).

√Heavy metals Precisely measure 25ml of this product, put it in a crucible, evaporate to dryness in a water bath, and check according to the law (Chinese Pharmacopoeia 2000 Edition, Appendix VIII H Second Method), the heavy metal content should not exceed 5ppm.

√Pyrogen: take this product, check according to the law (Chinese Pharmacopoeia 2000 edition two appendix XID), dosage is slowly injected 10ml per 1kg of rabbit body weight, should meet the regulations.

√Others: It should comply with the relevant provisions of injections (Appendix IB of Part Two of the Chinese Pharmacopoeia 2000 Edition).

Experimental example 2

This experimental example is the most preferred ginkgo pharmaceutical composition of the present invention large-capacity injection (each bottle contains ligustrazine phosphate (C ₈ H ₁₂ N ₂ ·H ₃ PO ₄ ·H ₂ O) 100mg, Ginkgo biloba extract (with Ginkgo biloba total flavonoids) 10mg, 2.25g sodium chloride) in the qualitative determination of the main components.

Take 2ml of this product and add 2 drops of potassium bismuth iodide to form an orange-red precipitate.

In the chromatogram recorded under the content determination items of ginkgo total flavonoids and ligustrazine phosphate, the retention time of the peak of the test product should be consistent with the corresponding peak retention time of the reference substance.

This product shows the differential reaction of sodium salt and chloride (Appendix III of Part Two of the Chinese Pharmacopoeia 2000 Edition).

Above 3 kinds of experiments are the qualitative responses of the components contained in the ginkgo medicinal composition of the present invention, indicating that the ginkgo medicinal composition of the present invention contains definite components.

Experimental example 3

This experimental example is the most preferred ginkgo pharmaceutical composition large volume injection of the present invention (each bottle contains ligustrazine phosphate (C ₈ H ₁₂ N ₂ H ₃ PO ₄ H ₂ O) 100mg, ginkgo leaf extract (in total Flavonoids) 10mg, 2.25g sodium chloride) in the quantitative detection of components. Each ml contains 36-44 μg of total ginkgo flavonoids, and 0.36-0.44 mg of ligustrazine phosphate (C ₈ H ₁₂ N ₂ ·H ₃ PO ₄ ·H ₂ O).

Ginkgo total flavonol glycosides (Ginkgo total flavonoids) content determination according to high performance liquid chromatography (Chinese Pharmacopoeia 2000 edition two appendix VD) determination.

Chromatographic conditions and system suitability experiments Octadecylsilane bonded silica gel was used as filler; methanol-0.4% phosphoric acid (55:45) was used as mobile phase; detection wavelength was 368nm. The number of theoretical plates calculated based on the peak of quercetin should not be less than 2500, and the degree of separation calculated based on the peaks of quercetin and isorhamnetin should be greater than 1.5.

Preparation of Reference Substance Solution Accurately weigh quercetin, kaempferol and isorhamnetin reference substance dried by phosphorus pentoxide, add methanol to make a mixed solution containing 0.03mg, 0.03mg, 0.02mg per 1ml, as Reference substance solution.

Preparation of the test solution Precisely measure 100ml of this product, concentrate under reduced pressure at 50°C to about 5ml, add 8ml of methanol, 3ml of 18% hydrochloric acid, heat and reflux on a water bath for 1.5 hours, quickly cool to room temperature, and transfer to a 25ml measuring bottle. Add methanol to dilute to the mark, shake well, filter through a filter membrane (pore size not greater than 0.45 μm), and use it as the test solution.

Determination method Precisely draw 20μl each of the reference substance solution and the test solution, inject it into a high-performance liquid chromatograph, measure, calculate the contents of the three flavonoid aglycones, and convert them into total flavonoid glycosides by the following formula.

Total flavonol glycosides content = (quercetin content + kaempferin content + isorhamnetin content) × 2.51

Ligustrazine Phosphate Determination According to high performance liquid chromatography (Chinese Pharmacopoeia 2000 edition two appendix VD) determination.

Chromatographic conditions and system suitability test used octadecylsilane bonded silica gel as filler; methanol-water (50▲:50) as mobile phase; detection wavelength was 295nm. The number of theoretical plates should not be less than 2000 based on the peak of ligustrazine phosphate.

Determination method Take this product, add mobile phase to dissolve and dilute to a solution containing 20μg per 1ml, take 20μl and inject it into a liquid chromatograph, and record the chromatogram; another appropriate amount of ligustrazine phosphate reference substance is used for determination in the same method, using the external standard method Calculated by peak area.

Through three batches of determination, the results of the content per ml are shown in Table 1:

Table 1

batch number Ginkgo biloba total flavonoids (μg) Ligustrazine Phosphate (mg) 20030701 39.0 0.41 20030702 38.2 0.38 20030703 39.2 0.39

Comparative example 1

This example is the most preferred pharmaceutical composition large-volume injection of the present invention (every bottle contains ligustrazine phosphate (C8H12N2 H3PO4 H2O) 100mg, Ginkgo biloba extract (calculated as total flavonoids of Ginkgo biloba) 10mg, 2.25g sodium chloride) and The clinical comparison of ginkgo leaf injection or ligustrazine phosphate injection in the treatment of ischemic cerebrovascular disease cerebral infarction alone shows the good curative effect of the pharmaceutical composition of the present invention, that is, the synergistic curative effect of ligustrazine phosphate and ginkgo leaf extract is better than Use ginkgo biloba injection or ligustrazine phosphate injection alone.

Control group 1: 32 cases, including 21 males and 11 females. Aged 43-72 years old, with an average of 57.5 years old.

Control group 2: 32 cases, including 20 males and 12 females. Aged 40-70 years old, with an average of 56.5 years old.

All cases were diagnosed by brain CT according to the diagnostic criteria of ischemic cerebrovascular disease established by the National Cerebrovascular Disease Academic Conference.

treatment method:

All patients in the treatment group were intravenously infused with the most preferred pharmaceutical composition of the present invention, large-capacity injection injection, one bottle at a time, once a day, for 3 weeks of treatment;

Control group 1 patient diluted 5ml of ginkgo biloba injection (containing 4.2mg of total flavonoids of ginkgo and 0.3mg of ginkgolides) with 250ml of 5% glucose injection, intravenous infusion, once a day, for 3 weeks.

Patients in control group 2 were treated with 100 mg of Ligustrazine Phosphate Injection diluted with 250 ml of 5% Glucose Injection, intravenously, once a day, for 3 weeks.

During the course of treatment, the three groups were given dehydrating agents, antibiotics, and maintenance of water and electrolyte balance and other corresponding treatments according to the needs of the disease.

Judgment of curative effect:

Significantly effective: the symptoms and signs basically disappeared or significantly improved, and the muscle strength of the paralyzed limbs increased by more than 2 grades; effective: the symptoms and signs improved, and the muscle strength of the paralyzed limbs improved by less than 2 grades; ineffective: the symptoms and signs did not change or aggravated.

Treatment results:

The effective rate and curative effect of the treatment group and the control group were compared, the effective rate of the treatment group and the control group was compared P<0.01, the difference was significant, the difference between the control group 1 and the control group 2 was not significant, the results are shown in Table 2.

Table 2 Comparison of curative effect between the treatment group and the control group

Control group 1 (n=32) Control group 2 (n=32) Treatment group (n=32) Significantly effective Ineffective Effective rate Number of cases 1312778.1 Number of cases 1313681.3 Number of cases 238196.9

Note: The comparison of curative effect between the two groups p<0.01

Comparative example 2

This example is the most preferred pharmaceutical composition large-volume injection of the present invention (every bottle contains ligustrazine phosphate (C8H12N2 H3PO4 H2O) 100mg, Ginkgo biloba extract (calculated as total flavonoids of Ginkgo biloba) 10mg, 2.25g sodium chloride) and Ginkgo biloba injection compares the clinical curative effect in the treatment of coronary heart disease angina pectoris, illustrates the good curative effect of pharmaceutical composition of the present invention, and the synergistic curative effect of i.e. Ligustrazine phosphate and Ginkgo leaf extract is better than using Ginkgo biloba injection (Shuxuening injection) alone ).

Clinical background: 90 cases of cerebral infarction patients with angina pectoris of coronary heart disease of Qi deficiency and blood stasis type were randomly divided into treatment group and control group.

60 patients in the treatment group, 34 males and 26 females, aged 40-72 years, with an average of 58 years old;

The control group consisted of 30 cases, including 21 males and 9 females. Aged 39-68 years old, with an average of 55.3 years old.

All cases were in line with the diagnostic criteria of coronary heart disease and angina pectoris of the Cardiovascular Professional Group of the National Internal Medicine Conference and the criteria of TCM syndrome differentiation of heart-qi deficiency and blood stasis.

treatment method:

The patients in the treatment group were intravenously infused with the most preferred pharmaceutical composition of the present invention, large volume injection injection, one bottle at a time, once a day, for 20 days of treatment;

Patients in the control group were diluted with 250ml of 5% glucose injection to dilute 5ml of Ginkgo biloba injection (containing 4.2mg of total ginkgo flavonoids and 0.3mg of ginkgolides), intravenously, once a day, and treated for 20 days.

Judgment of curative effect:

Markedly effective: the symptoms disappear or basically disappear, and the electrocardiogram returns to normal or roughly normal; effective: the number of angina attacks is significantly reduced, the degree is significantly reduced, the duration is significantly shortened, the ST segment of the electrocardiogram is lowered, and it rises above 0.5mv after treatment, and the main lead is inverted T Wave becomes shallow (up to 25%) or from flat to upright; invalid: no change in symptoms and ECG.

Treatment results:

In the treatment group, 34 cases were markedly effective, 22 cases were effective, and 4 cases were ineffective, with a total effective rate of 93.33%. In the control group, 10 cases were markedly effective, 13 cases were effective, and 7 cases were ineffective, with a total effective rate of 76.66%. There was a significant difference in the total effective rate between the two groups (P<0.05). The total effective rate of electrocardiogram: 60% in the treatment group, 53.33% in the control group, no significant difference between the two groups (P>0.05). Hemorrheology: After treatment, the indicators of whole blood viscosity, plasma viscosity, hematocrit, and fibrinogen in the treatment group all decreased significantly, and the indicators in the control group also decreased to a certain extent, and the difference between the two groups was significant (P <0.05).

Claims (10)

1, a kind of ginkgo medicine composition is characterized in that, pharmaceutical composition is made up of ligustrazine phosphate and Folium Ginkgo extract, and ligustrazine phosphate weight is 5-20 times of Folium Ginkgo extract weight, and Folium Ginkgo extract is in Ginkgo total flavones.

2, ginkgo medicine composition according to claim 1 is characterized in that, ligustrazine phosphate weight is 10 times of Folium Ginkgo extract weight in the pharmaceutical composition, and Folium Ginkgo extract is in Ginkgo total flavones.

3, a kind of method for preparing claim 1 or 2 described ginkgo medicine compositions is characterized in that, comprises the steps:

Earlier Folium Ginkgo is extracted, the Folium Ginkgo alcohol reflux, the extracting solution thickening filtration, resin absorption, eluting, reconcentration is drying to obtain Folium Ginkgo extract, then Folium Ginkgo extract and ligustrazine phosphate is carried out proportioning and mixes, and adds the compositions that pharmaceutically acceptable adjuvant is made acceptable various dosage forms on the pharmaceutics again.

4, the preparation method of ginkgo medicine composition according to claim 3 is characterized in that, the concrete preparation process of described Folium Ginkgo extract is:

After Folium Ginkgo is pulverized, add 8-12 and doubly measure 60-75% ethanol, twice of 40-50 ℃ of reflux, extract,, each 2-5 hour, merge extractive liquid, filters, and is evaporated to extracting liquid volume 1/8-1/12, add the doubly water of concentrated liquid measure of 1-2, the reuse addition is that the filter aid that 1-2% concentrates liquid measure filters, and filtrate is through macroporous resin adsorption, and with the desorbing of 60-75% alcoholic solution, stripping liquid is evaporated to dried, and the Folium Ginkgo extract that must contain total flavones is standby.

According to the preparation method of claim 3 or 4 described ginkgo medicine compositions, it is characterized in that 5, the concrete preparation process of described Folium Ginkgo extract is:

After Folium Ginkgo is pulverized, add 8-12 and doubly measure 70% ethanol, twice of 50 ℃ of reflux, extract,, each 2-4 hour, merge extractive liquid, filters, and is evaporated to extracting liquid volume 1/8-1/10, the water that adds 1 times of concentrated liquid measure, the reuse addition is that 1% filter aid that concentrates liquid measure filters, and filtrate is through macroporous resin adsorption, and with 70% alcoholic solution desorbing, stripping liquid is evaporated to dried, and the Folium Ginkgo extract that must contain total flavones is standby.

According to the preparation method of claim 4 or 5 described ginkgo medicine compositions, it is characterized in that 6, described filter aid is sodalite or Pulvis Talci; Described macroporous resin is D101 type resin or HP-20 type resin.

According to the preparation method of any one described ginkgo medicine composition of claim 3-5, it is characterized in that 7, the dosage form that described preparation of pharmaceutical compositions becomes is lyophilized injectable powder, tablet, capsule, small-volume injection, bulk capacity injection.

8, the preparation method of ginkgo medicine composition according to claim 7 is characterized in that, contains an amount of sodium chloride in the described bulk capacity injection as isoosmotic adjusting agent.

9, claim 1 or 2 described ginkgo medicine compositions comprise the application of cerebral blood supply insufficiency, cerebral thrombosis, cerebral embolism, cerebral vasospasm, brain insufficiency, alzheimer disease, parkinson, apoplexy, hypertension, hyperlipidemia, arteriosclerosis, coronary heart disease, angina pectoris, each disease medicament aspect of myocardial infarction as preparation treatment ischemic cardio cerebrovascular diseases.

10, the microcirculation pathological changes that causes as preparation treatment hepatic fibrosis, diabetes of claim 1 or 2 described ginkgo medicine compositions, the application of each disease medicament aspect of vasculitis.