CN1634246A - Compound formulation of breviscapine and asarum herb for treating cardiovascular and cerebrovascular diseases and its preparing process - Google Patents

Compound formulation of breviscapine and asarum herb for treating cardiovascular and cerebrovascular diseases and its preparing process Download PDF

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Publication number
CN1634246A
CN1634246A CN 200410040776 CN200410040776A CN1634246A CN 1634246 A CN1634246 A CN 1634246A CN 200410040776 CN200410040776 CN 200410040776 CN 200410040776 A CN200410040776 A CN 200410040776A CN 1634246 A CN1634246 A CN 1634246A
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extract
radix paeoniae
paeoniae rubra
herba erigerontis
preparation
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于文勇
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Yunyanxichuang Medicinal Science And Technology Development Co Ltd Guiyang C
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Yunyanxichuang Medicinal Science And Technology Development Co Ltd Guiyang C
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Priority to CN 200410040776 priority Critical patent/CN1634246A/en
Publication of CN1634246A publication Critical patent/CN1634246A/en
Priority to CNB2005101062557A priority patent/CN100443095C/en
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Abstract

The invention relates to a compound formulation of breviscapine and asarum herb for treating cardiovascular and cerebrovascular diseases and its preparing process, wherein the formulation is prepared mainly from herb of shortcape fleabane and radix paeoniae rubrathe. The formulation can also be applied to the preparation of liver-kidney syndrome, diabetes and its complications.

Description

Compound recipe fleabane preparation of treatment cardiovascular and cerebrovascular disease and preparation method thereof
Technical field: the present invention is a kind of compound recipe fleabane preparation for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof, belongs to technical field of Chinese medicine.
Technical background: cardiovascular and cerebrovascular disease such as coronary heart disease, cerebral thrombosis, alzheimer disease etc. all are one of the most common and diseases that harm is maximum in the world today, have become human mortality's one of the main reasons in many countries; According to investigations, sickness rate in recent years has and increases trend year by year, and in, young patient constantly increases, ischemic cardiovascular and cerebral vascular disease has become commonly encountered diseases, the frequently-occurring disease of harm China people ' s health; Prevent and treat purpose in order to reach, a large amount of research has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; As: the applicant submit applications, number of patent application is: 200410040349.4, name is called " a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof ", its with oil lamp and Radix Salviae Miltiorrhizae as preparing raw material; Treatment for cardiovascular and cerebrovascular disease is effective in cure; But the applicant thinks by further experimentation, effective component in red sage is mainly adjacent benzene dihydroxy compounds such as water-soluble phenolic acids material original pair tea phenol aldehyde and liposoluble constituent cryptotanshinone etc., and the acid ingredient of original pair tea phenol aldehyde and some band phenolic hydroxyl groups is similar to the chemical constituent of tannin, physicochemical property is approaching, so in process for preparing injection liquid, desire to remove tannin, the water soluble ingredient that keeps Radix Salviae Miltiorrhizae is difficult, brings very big inconvenience for big production; The tannin of product can produce extremely strong zest in addition; And tannin is the active material of chemical property that polyhydroxy fragrant acid is formed, it enters and can be used as hapten behind the body and associate more macromolecular complex with the amino of plasma protein, cause allergy, cause anaphylactic shock, especially this situation danger close in injection that is to say with Radix Salviae Miltiorrhizae to have certain limitation as the preparation raw material; And the disclosed number of patent application of Chinese patent communique is: 03136116, name is called the application of " a kind of Chinese medicine preparation for the treatment of Blood Ropy disease and preparation method thereof ", what use is the Radix Paeoniae Alba, though the Radix Paeoniae Rubra and the Radix Paeoniae Alba are all Ranunculaceae Paeonia plant, its root is traditional Chinese crude drug, but the former has heat clearing away, blood circulation invigorating efficacies; And the latter have enrich blood, effect such as analgesia, for the treatment Blood Ropy disease, the Radix Paeoniae Alba also is not suitable for, many Chinese crude drug compatibilities have been used in this part invention, preparation more complicated, restive its quality of production.
Summary of the invention: the objective of the invention is to: a kind of compound recipe Herba Erigerontis Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof is provided; The present invention is directed to prior art, according to cardiovascular and cerebrovascular disease such as coronary heart disease, cerebral thrombosis, alzheimer disease etc. all contract because of blood vessel is narrow, reason such as blood flow minimizing causes the diseases induced principle of blood supply insufficiency, adopts Radix Paeoniae Rubra and Herba Erigerontis compatibility to make preparation; It has activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, improves blood circulation and metabolism.For example coronary heart disease is that coronary atherosclerosis causes myocardial ischemia, anoxia and the heart disease that causes, and two medicines share, and can play to improve the myocardial metabolism effect, increase coronary flow, and the blood that improves cardiac muscle is provided with the effect of allevating angina pectoris.The present invention not only has curative effect preferably for treating cardiovascular and cerebrovascular disease such as coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis, alzheimer disease etc., can also be used for the treatment of diseases such as hepatorenal syndrome, heart and lung diseases, diabetes and complication thereof.And the present invention Herba Erigerontis Herba Asari, the Radix Paeoniae Rubra selected for use, mainly containing Herba Erigerontis florigen, peoniflorin, technology is rationally feasible, can not produce the anaphylaxis material in the preparation process, and is more safe and effective, but the patients life-time service.
The present invention constitutes like this: calculate according to components by weight percent, it is mainly by 1~99 part of Herba Erigerontis, or corresponding the weight fraction Herba Erigerontis extract and 99~1 parts of Radix Paeoniae Rubra that obtain after extracting, or the Radix Paeoniae Rubra extract that corresponding weight fraction obtains after extraction is made.Say accurately: calculate according to components by weight percent, it is mainly by 20~80 parts of Herba Erigerontiss, or corresponding the weight fraction Herba Erigerontis extract and 80~20 parts of Radix Paeoniae Rubra that obtain after extracting, or the Radix Paeoniae Rubra extract that corresponding weight fraction obtains after extraction is made.Optimizing prescriptions is: calculate according to components by weight percent, it is by 50 parts of Radix Paeoniae Rubra, or corresponding the weight fraction Radix Paeoniae Rubra extract and 50 parts of Herba Erigerontiss that obtain after extracting, or the Herba Erigerontis extract that corresponding weight fraction obtains after extraction is made; Extract is: Herba Erigerontis extract can be the highly finished product of Herba Erigerontis alcohol extract, Herba Erigerontis water extract, Herba Erigerontis water extract-alcohol precipitation extract, Herba Erigerontis semi-bionic extraction thing, Herba Erigerontis supercritical extract or above extract; Radix Paeoniae Rubra extract can be the highly finished product of Radix Paeoniae Rubra alcohol extract, Radix Paeoniae Rubra water extract, Radix Paeoniae Rubra water extract-alcohol precipitation extract, Radix Paeoniae Rubra semi-bionic extraction thing, Radix Paeoniae Rubra supercritical extract or above extract.Preparation of the present invention is: injection, comprising: injection, powder pin, freeze-dried powder, tablet, capsule, granule, drop pill, pellet, soft capsule, dispersible tablet.
The preparation method of the compound recipe fleabane preparation of treatment cardiovascular and cerebrovascular disease of the present invention is: get Herba Erigerontis, pulverize, alcohol reflux is collected extracting solution, reclaims ethanol, re-refines, concentrates; Get Radix Paeoniae Rubra, alcohol reflux filters, and filtrate recycling ethanol is refining, and drying gets Radix Paeoniae Rubra extract, makes different preparations then respectively.Say accurately, the preparation method of the compound recipe fleabane preparation of treatment cardiovascular and cerebrovascular disease of the present invention is: get Herba Erigerontis, pulverize 60% alcohol reflux 3 times, each 1.5 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 80% alcohol reflux 2 times, each 1 hour, filter, D101 type macroporous adsorbent resin on the filtrate, 30% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Paeoniae Rubra extract, makes different preparations then respectively.
Get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, and add 0.9% sodium chloride, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boils 30 minutes, puts cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5~8.0, benefit adds to the full amount of water for injection, filtering with microporous membrane through 0.25~0.45 μ m, fill was sterilized 30 minutes, and was promptly got great transfusion preparation for 115 ℃.
Get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 7.5~8.0, in medicinal liquid: it is caffolding agent that the ratio of caffolding agent=1: 3 adds dextran, and mixing is through the filtering with microporous membrane of 0.25~0.45 μ m, fill, lyophilization, lyophilisation condition :-10 ℃ of pre-freezes 2 hours ,-45 ℃ of pre-freezes began evacuation after 5 hours, and be warming up to-35 ℃, kept 2 hours; Be warming up to-30 ℃, kept 6 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to-10 ℃, kept 12 hours; Be warming up to 0 ℃, kept 2 hours; Be warming up to 10 ℃, kept 2 hours; Be warming up to 20 ℃, kept 2 hours; Be warming up to 30 ℃, kept 2 hours, promptly get lyophilized injectable powder.
Get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, stir evenly, cold preservation filters, and filtrate adds 0.1% active carbon, boiled 30 minutes, put cold, be filtered to clear and bright, with 10%NaOH adjust pH 7.5~8.0, filtering with microporous membrane through 0.25~0.45 μ m, spray drying, packing promptly gets injectable powder.
Get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, add 0.1% active carbon, boiled 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5~8.0, benefit adds to the full amount of water for injection, filtering with microporous membrane through 0.25~0.45 μ m, fill was sterilized 30 minutes, and was promptly got injection for 115 ℃.
Compared with prior art, the applicant adopts Radix Paeoniae Rubra and Herba Erigerontis compatibility to make preparation, Radix Paeoniae Rubra, Herba Erigerontis Herba Asari have activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, improve blood circulation and metabolism, adapt to sanatory requirement more: for example coronary heart disease is that coronary atherosclerosis causes myocardial ischemia, anoxia and the heart disease that causes, two medicines share, and can play and improve myocardial metabolism effect, increase coronary flow, and the blood that improves cardiac muscle is provided with the effect of allevating angina pectoris.The present invention not only has curative effect preferably for treating cardiovascular and cerebrovascular disease such as coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis, alzheimer disease etc., can also be used for the treatment of diseases such as hepatorenal syndrome, heart and lung diseases, diabetes and complication thereof.For injection, safety is the most basic requirement, Herba Erigerontis Herba Asari, Radix Paeoniae Rubra that the present invention selects for use, mainly contain Herba Erigerontis florigen, peoniflorin,, can not produce the anaphylaxis material in the preparation process by reasonable feasible technology, guaranteed the safe and effective of product, but the patients life-time service.
The applicant finds in development process, though the effective site Radix Paeoniae Rubra total glycosides of Radix Paeoniae Rubra has adopted the macroporous resin enrichment effective ingredient, but its content is difficult to reach 50% of extract, find that by furtheing investigate the back effect of different model resin differs greatly, so determined best process for refining according to experiment, made the content of Radix Paeoniae Rubra total glycosides improve greatly; But the clarity of product is undesirable, the pseudocilium incidence rate is higher, find that by technology further being optimized screening the contained Herba Erigerontis florigen dissolubility in water of Herba Erigerontis is subjected to the pH value influence greatly, adjust to behind the rational pH value product lamp inspection qualification rate and show to annotate and improve.The present invention also provides the detailed processing technology of several formulations, can be directly used in and instruct actual production.
The applicant has carried out a series of experiments, can prove that medicine provided by the invention has effective effect; Experimental example 1: the pharmacodynamics comparative study of different formulations
(1) to the influence of stasis syndrome rat blood rheological characteristic: 70 of rats, male and female half and half, body weight 270 ± 20g successive administration 12 days, 1h after the last administration, all the other respectively organize equal sc injection epinephrine 0.8mg/kg, totally twice, two minor tick 4h except that the normal control group.(front and back each 2 hours at interval) immerse 5min in the frozen water, fasting with rat between twice.Femoral artery blood sampling in morning next day, each index of hemorheology is measured in the heparin sodium anticoagulant.
Group plasma viscosity packed cell volume reduced viscosity
Normal control 1.52 ± 0.34 0.43 ± 0.11 7.78 ± 0.29
Model contrast 2.15 ± 0.18 0.55 ± 0.04 8.39 ± 3.43
Radix Paeoniae Rubra 2g/kg 1.96 ± 0.24 0.48 ± 0.27 8.20 ± 2.54
Herba Erigerontis 2g/kg 1.81 ± 0.18 0.45 ± 0.08 8.10 ± 1.72
Oil lamp Radix Salviae Miltiorrhizae extract 1.78 ± 0.27 0.44 ± 0.39 7.99 ± 1.33
Oil lamp Radix Paeoniae Alba extracting solution 1.77 ± 0.45 0.44 ± 0.87 8.01 ± 1.33
Oil lamp Radix Paeoniae Rubra extracting solution 1.68 ± 0.19 0.43 ± 0.15 7.81 ± 1.64
(2) to the influence of blood stasis model rabbit blood rheological characteristic
48 of rabbit are divided into 6 groups at random, and 8 every group, ♀ ♂ half and half is respectively blank group, model control group, positive drug control group, Radix Paeoniae Rubra group, Herba Erigerontis group, oil lamp Radix Paeoniae Rubra group.Each treated animal elder generation auricular vein is injected (iv) administration.Blank and model control group injecting normal saline (NS) 1ml/kg, positive drug group iv puerarin injection 30mg/kg (being made into 30mg/ml) with NS, experimental group is injected the medicinal liquid (being made into NF) of 0.25mg/ml respectively, dosage is 1ml/kg, two weeks of successive administration (14d), in administration the 2nd, 13d, except that the blank group, each rabbit is annotated 10% high molecular dextran 5ml/kg through auricular vein respectively, every day twice, causes blood stasis model.After the last administration, inject 10% high molecular dextran 5ml/kg once more, behind the 15min, heart is taked fasting blood 6ml, carrying out hemorheology index detects, wherein platelet aggregation rate adopts turbidimetry for Determination: the rotary cone-plate viscosity apparatus mensuration of other employing LBY-N6A+ with LBY-NJ2 type platelet aggregation instrument.
To rabbit platelet aggregation and fibrinogenic influence (x ± s, n=6)
Group dosage body weight (kg) platelet aggregation (%) Fibrinogen (g/L)
Blank group-2.41 ± 0.22 16.33 ± 1.73 2.87 ± 3.18
Model group-2.49 ± 0.16 39.06 ± 17.13 2.65 ± 1.29
Positive drug group 30mg/kg 2.38 ± 0.15 12.48 ± 0.36 3.04 ± 2.88
Radix Paeoniae Rubra group 2g/kg 2.46 ± 0.27 15.11 ± 0.23 2.79 ± 1.53
Herba Erigerontis group 2g/kg 2.44 ± 0.13 14.89 ± 0.40 2.73 ± 0.87
Oil lamp Radix Paeoniae Rubra group 2g/kg 2.35 ± 0.39 13.72 ± 3.05 2.65 ± 2.32
The result shows that the Herba Erigerontis main component is the breviscapine total flavones, and chemistry is by name 4,5,6-trihydroxyflavone-7-glucuronide, have suppress that platelet is gathered, anticoagulant function, microcirculation improvement effect, can suppress the transhipment of calcium pump to calcium ion; Radix Paeoniae Rubra can reduce the blood plasma lipide peroxide, reduces calcium and is deposited on arterial wall, influences calcium metabolism, the balance atherosclerosis; Behind Herba Erigerontis and the Radix Paeoniae Rubra compatibility ability of improving the blood stasis model blood status is more by force arranged, blood stasis rat plasma viscosity, packed cell volume, platelet aggregation are significantly reduced, prescription of the present invention can synergy, and curative effect is better than the oil lamp Radix Paeoniae Alba, oil lamp Radix Salviae Miltiorrhizae prescription.
Experimental example 2: refining pure metallization processes research: the applicant has carried out the different model macroporous adsorbent resin to the result of study of Radix Paeoniae Rubra total glycosides than adsorbance.Weight than adsorbance (absorption saponin amount with dried resin weight ratio)=(for the amount of the amount of saponin in the upper prop liquid-be saponin in the post effluent-be the amount of saponin in the water elution liquid)/dried resin.
1. the comparison of process for purification: n-butanol extraction: precision is measured Radix Paeoniae Rubra extract, extracts 3 times with water saturated n-butyl alcohol jolting, merges n-butyl alcohol liquid, and evaporate to dryness, residue add methanol makes dissolving; Macroporous adsorbent resin method precision is measured the Radix Paeoniae Rubra extracting solution, be added on the D101 resin column of pre-treatment, reuse 95% ethanol elution, collect eluent to effluent colourless till.
Total glycosides content % in the process for purification yield % extract
Ethyl acetate extraction method 0.90 42.52
Macroporous adsorbent resin method 1.21 69.46
2. the selection of resin model
The resin model compares adsorbance
D101 41.5
D605 55.1
AB-8 60.8
The result shows that refining pure metallization processes of the present invention is rationally feasible.
Experimental example 3: Study on Forming
(1) pH value is to the influence of injection: the applicant finds in development, the clarity of product is undesirable, the pseudocilium incidence rate is higher, find by technology further being optimized screening, the contained Herba Erigerontis florigen dissolubility in water of Herba Erigerontis is subjected to pH value influence greatly, adjusts to behind the rational pH value product lamp inspection qualification rate and shows to annotate and improve, the applicant placed 3 months for 40 ℃ the injection of 7 kinds of different pH value, investigated its stability respectively.
0 month March
PH value clarity lamp inspection rate % clarity lamp inspection rate %
Differ from 50.20 5.5 differ from 58.56
Differ from 60.52 6.0 differ from 67.32
Differ from 70.33 6.5 differ from 78.25
7.0 clear and bright 79.36 differ from 74.85
7.5 clear and bright 94.12 clear and bright 93.81
8.0 clear and bright 94.05 clear and bright 93.96
8.5 clear and bright 90.11 differ from 80.34
(2) pH value is to the influence of freeze-dried powder
Number 123456789
PH value of solution 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 before the lyophilizing
The good good job of insufficient formability difference difference difference difference is poor
The yellowish yellowish yellowish yellowish-brown deep yellow palm fibre of color and luster
PH value of solution 4.5 5.2 5.6 6.3 6.7 7.4 7.8 8.1 8.8 after the lyophilizing
The result shows that technology of the present invention is rationally feasible, and product quality is good.
Experimental example 4: preparation pharmacodynamic study
(1) to the influence of blood stasis model rabbit blood rheological characteristic
40 of rabbit are divided into 4 groups at random, and 8 every group, ♀ ♂ half and half is respectively blank group, model control group, positive drug control group and injection group of the present invention.Each treated animal elder generation auricular vein is injected (iv) administration.Blank and model control group injecting normal saline (NS) 1ml/kg, positive drug group iv puerarin injection 30mg/kg (being made into 30mg/ml) with NS, experimental group is injected the medicinal liquid (being made into NF) of 0.25mg/ml respectively, dosage is 1ml/kg, two weeks of successive administration (14d), in administration the 2nd, 13d, except that the blank group, each rabbit is annotated 10% high molecular dextran 5ml/kg through auricular vein respectively, every day twice, causes blood stasis model.After the last administration, inject 10% high molecular dextran 5ml/kg once more, behind the 15min, heart is taked fasting blood 6ml, carrying out hemorheology index detects, wherein platelet aggregation rate adopts turbidimetry for Determination: the rotary cone-plate viscosity apparatus mensuration of other employing LBY-N6A+ with LBY-NJ2 type platelet aggregation instrument.
To rabbit platelet aggregation and fibrinogenic influence (x ± s, n=6)
Group dosage (mg/kg) body weight (kg) platelet aggregation (%) Fibrinogen (g/L)
Blank group-2.31 ± 0.15 15.54 ± 2.46 2.53 ± 1.16
Model group-2.45 ± 0.08 38.27 ± 15.05 2.73 ± 1.41
Positive drug group 30 2.37 ± 0.11 12.74 ± 3.47 3.12 ± 1.83
Experimental group 0.25 2.32 ± 0.24 14.80 ± 1.36 2.69 ± 2.32 of the present invention
The result shows: preparation of the present invention is good to the blood stasis type curative effect of disease.
(2) to the effect of rat chronic hepatic injury
Healthy Wistar rat, body weight 120~160g is divided into 4 groups: normal control group, CCl at random 4Model group, injectable powder group of the present invention.Adopt CCl 4Preparation rat liver fibrosis model, colchicine group, compatibility group are gastric infusion, injectable powder 3.40g/kg of the present invention in beginning administration in the 1st day of modeling; Normal control group, CCl 4Model group gives the 0.9%NaCl solution of equivalent.Each treated animal is sacrificed by decapitation behind modeling 10w.Get blood system from the determination of serum liver function.
Each organizes rats'liver changes of function (x ± s)
Group n ALT (IU/L) Glb (ρ B/g/L) Alb (ρ B/g/L)
Normal group 10 35.50 ± 2.42 25.74 ± 2.13 34.20 ± 1.57
Model group 9 115.27 ± 11.28 32.58 ± 3.19 26.95 ± 2.14
Injectable powder group 11 59.72 of the present invention ± 13.39 26.23 ± 2.80 33.01 ± 3.63
The result shows that preparation of the present invention is the hepatic injury effect of being significantly improved to rat chronic.
Concrete embodiment:
Embodiments of the invention 1: Herba Erigerontis 10g, Radix Paeoniae Rubra 990g
Get Herba Erigerontis, pulverize, 60% alcohol reflux 3 times, each 1.5 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, and vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 80% alcohol reflux 2 times, each 1 hour, filter, D101 type macroporous adsorbent resin on the filtrate, 30% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Paeoniae Rubra extract; Get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, and add 0.9% sodium chloride, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boils 30 minutes, puts cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5~8.0, benefit adds to the full amount of water for injection, filtering with microporous membrane through 0.25~0.45 μ m, fill was sterilized 30 minutes, and was promptly got great transfusion preparation for 115 ℃.
Embodiments of the invention 2: Herba Erigerontis 990g, Radix Paeoniae Rubra 10g
Get Herba Erigerontis, pulverize, 60% alcohol reflux 3 times, each 1.5 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, and vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 80% alcohol reflux 2 times, each 1 hour, filter, D101 type macroporous adsorbent resin on the filtrate, 30% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Paeoniae Rubra extract; Get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 7.5~8.0, in medicinal liquid: it is caffolding agent that the ratio of caffolding agent=1: 3 adds dextran, and mixing is through the filtering with microporous membrane of 0.25~0.45 μ m, fill, lyophilization, lyophilisation condition :-10 ℃ of pre-freezes 2 hours ,-45 ℃ of pre-freezes began evacuation after 5 hours, and be warming up to-35 ℃, kept 2 hours; Be warming up to-30 ℃, kept 6 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to-10 ℃, kept 12 hours; Be warming up to 0 ℃, kept 2 hours; Be warming up to 10 ℃, kept 2 hours; Be warming up to 20 ℃, kept 2 hours; Be warming up to 30 ℃, kept 2 hours, promptly get lyophilized injectable powder.
Embodiments of the invention 3: Herba Erigerontis 800g, Radix Paeoniae Rubra 200g
Get Herba Erigerontis, pulverize, 60% alcohol reflux 3 times, each 1.5 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, and vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 80% alcohol reflux 2 times, each 1 hour, filter, D101 type macroporous adsorbent resin on the filtrate, 30% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Paeoniae Rubra extract; Get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, stir evenly, cold preservation filters, and filtrate adds 0.1% active carbon, boiled 30 minutes, put cold, be filtered to clear and bright, with 10%NaOH adjust pH 7.5~8.0, filtering with microporous membrane through 0.25~0.45 μ m, spray drying, packing promptly gets injectable powder.
Embodiments of the invention 4: Herba Erigerontis 200g, Radix Paeoniae Rubra 800g
Get Herba Erigerontis, pulverize, 60% alcohol reflux 3 times, each 1.5 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, and vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 80% alcohol reflux 2 times, each 1 hour, filter, D101 type macroporous adsorbent resin on the filtrate, 30% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Paeoniae Rubra extract; Get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, add 0.1% active carbon, boiled 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5~8.0, benefit adds to the full amount of water for injection, filtering with microporous membrane through 0.25~0.45 μ m, fill was sterilized 30 minutes, and was promptly got injection for 115 ℃.
Embodiments of the invention 5: Herba Erigerontis 500g, Radix Paeoniae Rubra 500g
Get Herba Erigerontis, pulverize, 20% alcohol reflux 0.5 hour is collected extracting solution, reclaims ethanol, the reuse ethyl acetate extraction, and extract concentrates, and vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 20% alcohol reflux 0.5 hour filters, D101 type macroporous adsorbent resin on the filtrate, 10% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Paeoniae Rubra extract, gets Herba Erigerontis extract, Radix Paeoniae Rubra extract, add the soybean oil mixing, the pressing pill promptly gets soft capsule, this product oral, three times on the one, each 2.
Embodiments of the invention 6: Herba Erigerontis 500g, Radix Paeoniae Rubra 500g
Get Herba Erigerontis, pulverize, 80% alcohol reflux 5 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, and vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 90% alcohol reflux 5 times, each 5 hours, filter D101 type macroporous adsorbent resin on the filtrate, 50% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Paeoniae Rubra extract, get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add the PEG400 mixing, the dropping preparation method pill promptly gets drop pill.
Embodiments of the invention 7: Herba Erigerontis 500g, Radix Paeoniae Rubra 500g
Get Herba Erigerontis, pulverize, 60% alcohol reflux 3 times, each 1.5 hours, collect extracting solution, reclaim ethanol, macroporous adsorbent resin is refining, and vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 80% alcohol reflux 2 times, each 1 hour, filter, the filtrate ethyl acetate extraction gets Radix Paeoniae Rubra extract, gets Herba Erigerontis extract, Radix Paeoniae Rubra extract, adds 2% sodium carboxymethyl cellulose, extrudes-the spheronization pill, promptly gets pellet.
Embodiments of the invention 8: Herba Erigerontis 500g, Radix Paeoniae Rubra 500g
Get Herba Erigerontis, pulverize, 60% alcohol reflux 3 times, each 1.5 hours, collect extracting solution, reclaim ethanol, centrifuge refining, vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 80% alcohol reflux 2 times, each 1 hour, filter filtrate centrifuge refining, vacuum drying, get Radix Paeoniae Rubra extract, get Herba Erigerontis extract, Radix Paeoniae Rubra extract, mixing, add 3% methylcellulose, it is moistening to add water, makes granule, dry, add 1% carboxymethyl starch sodium, tabletting promptly gets dispersible tablet.

Claims (10)

1, a kind of compound recipe fleabane preparation for the treatment of cardiovascular and cerebrovascular disease is characterized in that: calculate according to components by weight percent, it mainly is made for 99~1 parts with 1~99 part of Herba Erigerontis and Radix Paeoniae Rubra.
2, according to the compound recipe fleabane preparation of the described treatment cardiovascular and cerebrovascular disease of claim 1, it is characterized in that: calculate according to components by weight percent, it mainly is made for 80~20 parts by 20~80 parts of Herba Erigerontiss and Radix Paeoniae Rubra.
3, according to the compound recipe fleabane preparation of claim 1 or 2 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: calculate according to components by weight percent, it mainly is made for 50 parts by 50 parts of Radix Paeoniae Rubra and Herba Erigerontis, the Radix Paeoniae Rubra and the Herba Erigerontis that use can be medical material or extract, and concrete extract is: the highly finished product of Herba Erigerontis alcohol extract, Herba Erigerontis water extract, Herba Erigerontis water extract-alcohol precipitation extract, Herba Erigerontis semi-bionic extraction thing, Herba Erigerontis supercritical extract or above extract; Radix Paeoniae Rubra extract is the highly finished product of Radix Paeoniae Rubra alcohol extract, Radix Paeoniae Rubra water extract, Radix Paeoniae Rubra water extract-alcohol precipitation extract, Radix Paeoniae Rubra semi-bionic extraction thing, Radix Paeoniae Rubra supercritical extract or above extract.
4, according to the compound recipe fleabane preparation of claim 1,2 or 3 described this treatment cardiovascular and cerebrovascular diseases, it is characterized in that: described preparation is: injection, comprising: injection, powder pin, freeze-dried powder, tablet, capsule, granule, drop pill, pellet, soft capsule or dispersible tablet.
5, as the preparation method of the compound recipe fleabane preparation of the described treatment cardiovascular and cerebrovascular disease of claim 1~4, it is characterized in that: get Herba Erigerontis, pulverize, alcohol reflux is collected extracting solution, reclaims ethanol, re-refines, concentrates; Get Radix Paeoniae Rubra, alcohol reflux filters, and filtrate recycling ethanol is refining, and drying gets Radix Paeoniae Rubra extract, makes different preparations then respectively.
6, according to the preparation method of the compound recipe fleabane preparation of the described treatment cardiovascular and cerebrovascular disease of claim 5, it is characterized in that: get Herba Erigerontis, pulverize 60% alcohol reflux 3 times, each 1.5 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, vacuum drying gets Herba Erigerontis extract; Get Radix Paeoniae Rubra, 80% alcohol reflux 2 times, each 1 hour, filter, D101 type macroporous adsorbent resin on the filtrate, 30% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Paeoniae Rubra extract, makes different preparations then respectively.
7, according to the preparation method of the compound recipe fleabane preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, and add 0.9% sodium chloride, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 7.5~8.0, benefit adds to the full amount of water for injection, through the filtering with microporous membrane of 0.25~0.45 μ m, fill, sterilized 30 minutes, and promptly got great transfusion preparation for 115 ℃.
8, preparation method according to the compound recipe fleabane preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Herba Erigerontis extract, Radix Paeoniae Rubra extract adds water for injection, stirs evenly, cold preservation, filter, filtrate adds 0.1% active carbon, boils 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5~8.0, by medicinal liquid: the ratio adding dextran of caffolding agent=1: 3 is a caffolding agent, mixing, through the filtering with microporous membrane of 0.25~0.45 μ m, fill, lyophilization, lyophilisation condition :-10 ℃ of pre-freezes 2 hours,-45 ℃ of pre-freezes began evacuation after 5 hours, and were warming up to-35 ℃, kept 2 hours; Be warming up to-30 ℃, kept 6 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to-10 ℃, kept 12 hours; Be warming up to 0 ℃, kept 2 hours; Be warming up to 10 ℃, kept 2 hours; Be warming up to 20 ℃, kept 2 hours; Be warming up to 30 ℃, kept 2 hours, promptly get lyophilized injectable powder.
9, according to the preparation method of the compound recipe fleabane preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boils 30 minutes, puts cold, be filtered to clear and bright, with 10%NaOH adjust pH 7.5~8.0, through the filtering with microporous membrane of 0.25~0.45 μ m, spray drying, packing promptly gets injectable powder.
10, according to the preparation method of the compound recipe fleabane preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Herba Erigerontis extract, Radix Paeoniae Rubra extract, add water for injection, add 0.1% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 7.5~8.0, benefit adds to the full amount of water for injection, through the filtering with microporous membrane of 0.25~0.45 μ m, fill, sterilized 30 minutes, and promptly got injection for 115 ℃.
CN 200410040776 2004-09-24 2004-09-24 Compound formulation of breviscapine and asarum herb for treating cardiovascular and cerebrovascular diseases and its preparing process Pending CN1634246A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1857293B (en) * 2005-05-08 2010-04-28 深圳市生物谷科技有限公司 Medicine composition containing wild astragaloside and paeoniforin
CN102846735A (en) * 2011-07-01 2013-01-02 贵阳医学院 Chinese medicinal formulation containing effective fractions for treating cerebrovascular diseases and preparation method thereof

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1857293B (en) * 2005-05-08 2010-04-28 深圳市生物谷科技有限公司 Medicine composition containing wild astragaloside and paeoniforin
CN102846735A (en) * 2011-07-01 2013-01-02 贵阳医学院 Chinese medicinal formulation containing effective fractions for treating cerebrovascular diseases and preparation method thereof

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