CN1634241A - Compound formulation of notoginseng for treating cardiovascular and cerebrovascular diseases and its preparing process - Google Patents
Compound formulation of notoginseng for treating cardiovascular and cerebrovascular diseases and its preparing process Download PDFInfo
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Abstract
The invention relates to a compound formulation of notoginseng for treating cardiovascular and cerebrovascular diseases and its preparing process, wherein the preparation is mainly prepared from ontoginseng and astragalus root, the preparation has the functions of promoting blood circulation and improving metabolism.
Description
Technical field: the present invention is a kind of compound formulation of notoginseng 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: number of patent application is: 03141834, name is called " capsule preparations of a kind of blood lipid regulation and blood pressure ".Under study for action, the clear people in this Shen finds only to adopt the Radix Astragali, Radix Notoginseng prescription product good effect, and 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, bring very big inconvenience for big production, tannin can produce extremely strong zest; 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; The inventor participated in once also having finished that a application number is 200410022503.5, name is called the patent application of " Chinese medicine preparation of a kind of antitumor and enhancing immunity and preparation method thereof ", this part patent application has used Radix Ginseng as one of raw material, the benefiting action of product is better, but treats the weak curative effect of cardiovascular and cerebrovascular disease.The applicant is further finding in the research: the people participates in the pharmacological action of Radix Notoginseng in tonification, there is similarity many aspects such as blood circulation promoting and blood stasis dispelling, but certain difference is arranged, experimental studies have found that Radix Notoginseng with the equal experiment condition of Radix Ginseng under, can play and the akin resisting fatigue of Radix Ginseng, anoxia enduring, the cold resistant effect, illustrate that Radix Notoginseng has the benefiting action similar to Radix Ginseng, and Radix Notoginseng has the ability of improving the anxious stasis of blood model of rat blood " dense; sticking; as to coagulate; poly-" state more by force, can make low whole blood viscosity and the plasma viscosity cut of blood stasis rat, packed cell volume significantly reduces, and red cell deformability is increased, the Radix Ginseng low dose then can only obviously reduce the low whole blood viscosity of cutting, and other blood index are not had obvious improvement effect, and the anxious toxicity of Radix Notoginseng total arasaponins is significantly less than Radix Ginseng total saponins; In order to reduce the drug administration amount, this product has adopted process for refining, but traditional impurity removal process is very limited for the accumulation ability of effective ingredient.In view of such circumstances, seek a kind of active drug for the treatment of cardiovascular and cerebrovascular disease, compatibility is simple, therapeutic effect is desirable, does not have toxic and side effects, the thing that preparation technology's rational and effective medicine preparation has become people to be badly in need of solving.
Summary of the invention: the objective of the invention is to: a kind of compound formulation of notoginseng for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof is provided; At prior art, the present invention 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 the Radix Astragali and Radix Notoginseng compatibility to make preparation; The product that obtains 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 diseases such as enhance immunity antitumor, treatment hepatorenal syndrome, heart and lung diseases, diabetes and complication thereof.And the present invention is a pure Chinese medicinal preparation, but the little patients life-time service of its untoward reaction, at selecting for use the Radix Astragali and Radix Notoginseng compatibility to make preparation, the present invention also provides preparation method, guarantee that the product of producing satisfies the treatment needs, can solve the problem that prior art exists.
The present invention constitutes like this: calculate according to components by weight percent, it is mainly by 1～99 part of Radix Notoginseng, or corresponding the weight fraction Radix Notoginseng extract and 99～1 parts of the Radixs Astragali that obtain after extracting, or the Radix Astragali 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 Radix Notoginseng, or corresponding the weight fraction Radix Notoginseng extract and 80～20 parts of the Radixs Astragali that obtain after extracting, or the Radix Astragali extract that corresponding weight fraction obtains after extraction is made.Best prescription is: calculate according to components by weight percent, it is by 50 parts of the Radixs Astragali, or corresponding the weight fraction Radix Astragali extract and 50 parts of Radix Notoginseng that obtain after extracting, or the Radix Notoginseng extract that corresponding weight fraction obtains after extraction is made.Preparation of the present invention is: injection, comprising: injection, powder pin, freeze-dried powder, tablet, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, pellet, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, soft extract, extractum and membrane.Say accurately: preparation of the present invention is: injection, comprising: injection, powder pin, freeze thousand powder pins, tablet, capsule, granule, drop pill, pellet, soft capsule, dispersible tablet.
Extract of the present invention is: Radix Notoginseng extract can be the highly finished product of Radix Notoginseng alcohol extract, pseudo-ginseng water extract, Radix Notoginseng water extract-alcohol precipitation extract, Radix Notoginseng semi-bionic extraction thing, Radix Notoginseng supercritical extract or above extract; Radix Astragali extract can be the highly finished product of (+)-Astragenol extract, Radix Astragali water extract, Radix Astragali water extract-alcohol precipitation extract, Radix Astragali semi-bionic extraction thing, Radix Astragali supercritical extract or above extract.The preparation method of the compound formulation of notoginseng of treatment cardiovascular and cerebrovascular disease of the present invention is: takes by weighing Radix Notoginseng, pulverizes, and alcohol reflux, the collection extracting solution filters, and reclaims ethanol, gets the Radix Notoginseng extracting solution, and macroporous adsorbent resin is refining, and drying gets Radix Notoginseng extract; Get the Radix Astragali, water boiling and extraction is filtered, and macroporous adsorbent resin is refining, and drying gets Radix Astragali extract; Make different preparations then respectively.Say that exactly the preparation method of the compound formulation of notoginseng of treatment cardiovascular and cerebrovascular disease of the present invention is got and taken by weighing Radix Notoginseng, pulverize, measure 80% alcohol reflux 3 times, each 1 hour for 8 times, collect extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, last D101 type macroporous adsorbent resin, 70% ethanol elution, eluent concentrating under reduced pressure, vacuum drying gets Radix Notoginseng extract; Get the Radix Astragali, 8 times of water gagings decoct and extract 3 times, and each 1 hour, filter, AB-8 type macroporous adsorbent resin on the filtrate, 95% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Astragali extract; Make different preparations then respectively.Concrete:
Get Radix Notoginseng extract, Radix Astragali extract, add water for injection, and add 0.9% sodium chloride, stir evenly, cold preservation filters, filtrate adds 0.2% active carbon, boils 30 minutes, puts cold, be filtered to clear and brightly, with 10%NaOH adjust pH 5.5～7.5, 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 Radix Notoginseng extract, Radix Astragali extract, add water for injection, stir evenly cold preservation, filter, filtrate adds 0.2% active carbon, boils 30 minutes, put cold, be filtered to clear and bright, with 10%NaOH adjust pH 5.5～7.5, in medicinal liquid: it is caffolding agent that the ratio of caffolding agent=2: 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 3 hours,-45 ℃ of pre-freezes began evacuation after 6 hours, and were warming up to-35 ℃, kept 3 hours; Be warming up to-30 ℃, kept 6 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to-10 ℃, kept 10 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 Radix Notoginseng extract, Radix Astragali extract, add water for injection, stir evenly, cold preservation filters, filtrate adds 0.2% active carbon, boils 30 minutes, put cold, be filtered to clear and bright, with 10%NaOH adjust pH 5.5～7.5, through the filtering with microporous membrane of 0.25～0.45 μ m, spray drying, packing promptly gets injectable powder.
Get Radix Notoginseng extract, Radix Astragali extract, add water for injection, add 0.2% active carbon, boiled 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 5.5～7.5, 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, product provided by the invention 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 diseases such as enhance immunity antitumor, treatment hepatorenal syndrome, heart and lung diseases, diabetes and complication thereof.And the present invention is pure Chinese medicinal preparation, but the little patients life-time service of its untoward reaction; The present invention selects the Radix Notoginseng that similarity is arranged aspect many at tonification, blood circulation promoting and blood stasis dispelling etc. with Radix Ginseng for use, and discover by experiment Radix Notoginseng with the equal experiment condition of Radix Ginseng under, can play and the akin resisting fatigue of Radix Ginseng, anoxia enduring, cold resistant effect, illustrate that Radix Notoginseng has the benefiting action similar to Radix Ginseng; And Radix Notoginseng has the ability of improving the anxious stasis of blood model of rat blood " dense, sticking, coagulate, gather " state more by force, can make that the blood stasis rat is low to cut whole blood viscosity and plasma viscosity, packed cell volume significantly reduce, and red cell deformability is increased, the improvement effect obviously is better than Radix Ginseng, and the anxious toxicity of Radix Notoginseng total arasaponins is significantly less than Radix Ginseng total saponins.
The applicant screens by experiment, has adopted the macroporous resin enrichment effective ingredient, and finds that the effect of the resin of different model differs greatly, and the applicant is determined by experiment best process for refining; The applicant also is determined by experiment the suitable pH value of injection, guaranteed the stable of Radix Notoginseng, Radix Astragali effective ingredient.The applicant does not adopt Radix Salviae Miltiorrhizae, and be to use Radix Notoginseng, Radix Astragali prescription preparing product, curative effect ideal not only, and do not have a large amount of tannins that Danshen root injection is difficult to remove in the preparation process, safety and stability more, solved the problem that prior art exists, the present invention also provides the detailed processing technology of several formulations, can be directly used in and instruct actual production; Reached the purpose of invention.
The applicant has carried out a series of experiments, can prove that medicine provided by the invention has effective effect; Experimental example 1: the people participates in the pharmacodynamics comparative study of Radix Notoginseng
(1) comparative study of benefiting action
1. to the influence of mice swimming time: 30 of mices, body weight 22.0 ± 1.4g, male and female half and half are divided into 3 groups at random.Ig gives medicine or equal-volume normal saline respectively, and 1h after the administration is stained with the clay that is equivalent to from heavy sensation of the whole body 10% at each mouse tail, puts into basin, makes its free swimming, picks up counting, and a submerged 10s can not emerge to mice, stops timing.The record respectively organize the mice swimming time (x ± s, min), matched group is 5.38 ± 3.02 as a result, Radix Ginseng 6g/kg is 8.71 ± 2.86, Radix Notoginseng 6g/kg is 8.65 ± 2.55.The result shows that the people participates in the trip ice time that Radix Notoginseng all can obviously prolong mice.
2. to the influence of mice normal pressure hypoxia-bearing capability: get 30 of mices, body weight 22.3 ± 1.6g, male and female half and half, grouping is the same with medication.1h after the administration puts into the 250ml wide mouthed bottle that fills the 10g sodica calx respectively with mice, and the bottleneck of obturaging picks up counting simultaneously.With the respiratory arrest is index, and the record mouse diing time (x ± s, min), matched group is 31.04 ± 3.12 as a result, and Radix Ginseng 6g/kg is 35.27 ± 2.04, and Radix Notoginseng 6g/kg is 34.98 ± 2.57.The result shows that the people participates in Radix Notoginseng all can obviously prolong the time-to-live of mice under the normobaric hypoxia condition.
The result shows, Radix Ginseng, Radix Notoginseng benefiting action are similar.
(2) acute toxicity testing: Kunming mouse, 10 every group, male and female half and half, the administration of intraperitoneal single injection is observed reaction of animals and is write down the animal dead situation behind the medicine, obtain LD
50
Radix Notoginseng total arasaponins and Radix Ginseng total saponins get LD
50Be respectively 826.8 (730.5-928.9) and 624.8 (559.7-677.3) mg/kg, behind the heavy dose of Radix Notoginseng total arasaponins and Radix Ginseng total saponins lumbar injection, mice is movable significantly to be reduced, hypopnea, death is mainly in behind the medicine 2-3 days, and the postmortem naked eyes are not seen obvious organ disease, with the LD of two medicines
50Value is carried out the t check, and the two has significant difference.Experimental result shows that the acute toxicity of Radix Notoginseng total arasaponins is less than Radix Ginseng total saponins.
(3) to the influence of stasis syndrome rat blood rheological characteristic: 60 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 1.54 ± 0.25 0.43 ± 0.02 7.69 ± 0.86
Model contrast 2.13 ± 0.15 0.52 ± 0.04 8.54 ± 2.51
Radix Ginseng 2g/kg 1.97 ± 0.21 0.49 ± 0.04 8.40 ± 1.33
Radix Notoginseng 2g/kg 1.80 ± 0.16 0.44 ± 0.05 8.10 ± 2.72
RENSHEN HUANGQI ZHUSHEYE 1.79 ± 0.22 0.44 ± 0.01 8.04 ± 1.26
Radix Notoginseng Radix Astragali injection 1.75 ± 0.14 0.43 ± 0.05 7.95 ± 1.75
The result shows, Radix Notoginseng has the ability of improving the anxious stasis of blood model of rat blood status more by force, blood stasis rat plasma viscosity, packed cell volume are significantly reduced, the Radix Ginseng low dose does not have obvious improvement effect to other blood index, and preparation of the present invention is better than the Radix Ginseng formulation of astragalus root to the effect of stasis syndrome rat blood rheological characteristic.
Experimental example 2: refining pure metallization processes research: the applicant has carried out different process for purification and different model macroporous adsorbent resin to the Radix Astragali, Radix Notoginseng total arasaponins enrichment and than the result of study of 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) Radix Astragali saponin purifying process research:
1. the comparison of process for purification:
Saponin content % in the process for purification yield % total extract
Extraction 0.89 70.50
Macroporous adsorbent resin method 1.31 82.23
2. the selection of resin model
The resin model compares adsorbance
D101 68.5
D605 45.9
AB-8 80.2
(2) arasaponin purifying process research:
1. the comparison of process for purification: n-butanol extraction: precision is measured Radix Astragali 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 Radix Astragali extractive solution, be added on the AB-8 resin column of pre-treatment, reuse 95% ethanol elution, collect eluent to effluent colourless till.
Saponin content % in the process for purification yield % total extract
N-butanol extraction 0.90 79.52
Macroporous adsorbent resin method 1.21 80.46
2. the selection of resin model
The resin model compares adsorbance
D101 81.5
D605 55.1
AB-8 40.8
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, product arasaponin of the present invention, Radix Astragali saponin are one of main onset composition, because of facile hydrolysis causes the medicine instability, its drug effect reduces, suitable acid-base value is the stable key factor of medicine, in order to improve the quality of this injection, the applicant placed 3 months for 40 ℃ the injection of 6 kinds of different pH value, investigated its stability respectively.
0 month March
PH value clarity total saponins (mg/ml) clarity total saponins (mg/ml)
Differ from 1.02 5.0 differ from 1.52
5.5 clear and bright 1.50 clear and bright 1.47
6.0 clear and bright 1.50 clear and bright 1.46
6.5 clear and bright 1.48 clear and bright 1.46
7.0 clear and bright 1.49 clear and bright 1.41
7.5 clear and bright 1.49 clear and bright 1.47
Differ from 1.21 8.0 differ from 1.57
(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 job difference is poor carefully for insufficient formability
The yellowish yellowish yellowish-brown deep yellow palm fibre of color and luster
PH value of solution 4.8 5.3 5.7 6.3 6.5 7.2 7.5 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
Test 1 group: Radix Notoginseng injection; Test 2 groups: Radix Astragali injection; Test 3 groups: injection of the present invention
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 and tests 1,2,3 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.Behind the last administration h, 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
Test 1 group 0.25 2.32 ± 0.24 14.80 ± 1.36 2.69 ± 2.32
Test 2 group 0.25 2.38 ± 0.18 14.58 ± 4.08 2.58 ± 1.29
Test 3 group 0.25 2.35 ± 0.35 13.03 ± 3.71 2.53 ± 2.35
The result shows: preparation good effect of the present invention, be better than single medicinal material, and prescription has the effect of Synergistic.
(2) experimentation of treatment rat diabetes nephropathy
Select 30 of the healthy male Wistar rats of 150～190g for use, be divided into normal control group, diabetic groups and powder acupuncture treatment group of the present invention at random, every group 10, divide cage to feed, arbitrarily drink water, with diabetes rats, fasting 10h, be dissolved in 0.1mol/L citric acid sodium citrate buffer solution (pH4.5) with streptozotocin, be made into 1% solution, press the 50mg/kg single intraperitoneal injection, get tail vein behind the 5d, measure blood glucose with blood glucose meter, blood glucose 〉=16.7mmol/L is diabetes rat (becoming mould rate 100%).The citric acid citrate buffer solution of normal control group injection respective volume.Injectable powder of the present invention is become 0.5g/L solution with physiological saline solution, the treatment group is pressed 70mgkg-1d-1 dosage filling stomach morning every day, and the diabetic groups stomach is raised the normal saline of equivalent, continues to feed to 12 all backs collect specimens, metabolic cage is collected 24h urine, surveys 24h excretion quantity of urinary protein (UPE).Claim to anaesthetize after the quality, right atrium is got blood and is surveyed Endothelin, puts the method for exempting from and measures insulin, surveys blood urea nitrogen (BUN) with the CX7 automatic biochemistry analyzer, and calculates endogenous creatinine clearance rate (Ccr), and the result proofreaies and correct with the body constitution amount.Get two kidneys, right kidney part is fixed with 4% paraformaldehyde, conventional film-making, and light microscopy checking is measured MGPA and MGV with image analyzer, and left kidney is used to organize the ET assay.
Normal control group diabetic groups injectable powder group of the present invention
MGPA 51.14±3.56 65.26±4.25 53.13±0.15
MGV 430.4±36.5 648.2±23.2 446.2±13.7
BUN 7.26±0.65 11.30±1.43 8.14±1.04
Ccr 5.10±0.75 2.62±0.12 4.35±0.15
UPE 9.24±1.20 42.78±10.10 19.17±1.38
The result shows that preparation of the present invention all significantly improves than the diabetic nephropathy rat for MGPA, MGV, BUN, Ccr and 24h excretion quantity of urinary protein.
Concrete embodiment:
Embodiments of the invention 1: Radix Notoginseng 10g, Radix Astragali 990g
Get and take by weighing Radix Notoginseng, pulverize, measure 80% alcohol reflux 3 times for 8 times, each 1 hour, collect extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, last D101 type macroporous adsorbent resin, 70% ethanol elution, the eluent concentrating under reduced pressure, vacuum drying gets Radix Notoginseng extract; Get the Radix Astragali, 8 times of water gagings decoct and extract each 1 hour 3 times, filter AB-8 type macroporous adsorbent resin on the filtrate, 95% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying, get Radix Astragali extract, get Radix Notoginseng extract, Radix Astragali extract adds water for injection, and add 0.9% sodium chloride, stir evenly cold preservation, filter, filtrate adds 0.2% active carbon, boils 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 5.5～7.5, 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: Radix Notoginseng 990g, Radix Astragali 10g
Get and take by weighing Radix Notoginseng, pulverize, measure 80% alcohol reflux 3 times for 8 times, each 1 hour, collect extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, last D101 type macroporous adsorbent resin, 70% ethanol elution, the eluent concentrating under reduced pressure, vacuum drying gets Radix Notoginseng extract; Get the Radix Astragali, 8 times of water gagings decoct and extract each 1 hour 3 times, filter AB-8 type macroporous adsorbent resin on the filtrate, 95% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying, get Radix Astragali extract, get Radix Notoginseng extract, Radix Astragali extract adds water for injection, stir evenly, cold preservation filters, filtrate adds 0.2% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 5.5～7.5, in medicinal liquid: it is caffolding agent that the ratio of caffolding agent=2: 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 3 hours ,-45 ℃ of pre-freezes began evacuation after 6 hours, and be warming up to-35 ℃, kept 3 hours; Be warming up to-30 ℃, kept 6 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to-10 ℃, kept 10 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: Radix Notoginseng 800g, Radix Astragali 200g
Get and take by weighing Radix Notoginseng, pulverize, measure 80% alcohol reflux 3 times for 8 times, each 1 hour, collect extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, last D101 type macroporous adsorbent resin, 70% ethanol elution, the eluent concentrating under reduced pressure, vacuum drying gets Radix Notoginseng extract; Get the Radix Astragali, 8 times of water gagings decoct and extract each 1 hour 3 times, filter AB-8 type macroporous adsorbent resin on the filtrate, 95% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying, get Radix Astragali extract, get Radix Notoginseng extract, Radix Astragali extract, add water for injection, stir evenly, cold preservation filters, and filtrate adds 0.2% active carbon, boiled 30 minutes, put cold, be filtered to clear and bright, with 10%NaOH adjust pH 5.5～7.5, filtering with microporous membrane through 0.25～0.45 μ m, spray drying, packing promptly gets injectable powder.
Embodiments of the invention 4: Radix Notoginseng 200g, Radix Astragali 800g
Get and take by weighing Radix Notoginseng, pulverize, measure 80% alcohol reflux 3 times for 8 times, each 1 hour, collect extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, last D101 type macroporous adsorbent resin, 70% ethanol elution, the eluent concentrating under reduced pressure, vacuum drying gets Radix Notoginseng extract; Get the Radix Astragali, 8 times of water gagings decoct and extract each 1 hour 3 times, filter AB-8 type macroporous adsorbent resin on the filtrate, 95% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Astragali extract, get Radix Notoginseng extract, Radix Astragali extract, add water for injection, add 0.2% active carbon, boiled 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 5.5～7.5, 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: Radix Notoginseng 500g, Radix Astragali 500g
Get and take by weighing Radix Notoginseng, pulverizing is measured 20% alcohol reflux 1 time for 3 times, and each 2 hours, collect extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, centrifugal remove impurity gets Radix Notoginseng extract; Get the Radix Astragali, 3 times of water gagings decoct and extract 2 times, each 2 hours, filter, the centrifugal remove impurity of filtrate gets Radix Astragali extract, gets Radix Notoginseng extract, Radix Astragali extract, adds 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: Radix Notoginseng 500g, Radix Astragali 500g
Get and take by weighing Radix Notoginseng, pulverizing is measured 95% alcohol reflux 5 times for 15 times, and each 3 hours, the collection extracting solution filtered, and reclaims ethanol, gets the Radix Notoginseng extracting solution, and extraction is made with extra care, and gets Radix Notoginseng extract; Get the Radix Astragali, 15 times of water gagings decoct and extract 5 times, and each 3 hours, filter, organic solvent extraction gets Radix Astragali extract, gets Radix Notoginseng extract, Radix Astragali extract, adds the PEG4000 mixing, and the dropping preparation method pill promptly gets drop pill.
Embodiments of the invention 7: Radix Notoginseng 500g, Radix Astragali 500g
Get and take by weighing Radix Notoginseng, pulverizing is measured 50% alcohol reflux 2 times for 10 times, and each 2 hours, the collection extracting solution filtered, and reclaims ethanol, gets the Radix Notoginseng extracting solution, and chromatography is made with extra care, and gets Radix Notoginseng extract; Get the Radix Astragali, 10 times of water gagings decoct and extract 2 times, and each 2 hours, filter, macroporous adsorbent resin is refining, gets Radix Astragali extract, gets Radix Notoginseng extract, Radix Astragali extract, adds 4% sodium carboxymethyl cellulose, extrudes-the spheronization pill, promptly gets pellet.
Embodiments of the invention 8: Radix Notoginseng 500g, Radix Astragali 500g
Get and take by weighing Radix Notoginseng, pulverize, measure 80% alcohol reflux 3 times for 8 times, each 1 hour, collect extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, last D101 type macroporous adsorbent resin, 70% ethanol elution, the eluent concentrating under reduced pressure, vacuum drying gets Radix Notoginseng extract; Get the Radix Astragali, 8 times of water gagings decoct and extract 3 times, each 1 hour, filter, AB-8 type macroporous adsorbent resin on the filtrate, 95% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Astragali extract, get Radix Notoginseng extract, Radix Astragali extract, mixing adds 3% methylcellulose, it is moistening to add water, makes granule, drying, add 2% carboxymethyl starch sodium, tabletting promptly gets dispersible tablet.
Claims (10)
1, a kind of compound formulation of notoginseng for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it is mainly by 1～99 part of Radix Notoginseng, or 99～1 parts of the Radix Notoginseng extract that after extracting, obtains of corresponding weight fraction and the Radixs Astragali, or the Radix Astragali extract that corresponding weight fraction obtains after extracting is made into injection, comprise: injection, the powder pin, freeze-dried powder, tablet, dispersible tablet, capsule, soft capsule, microcapsule, granule, pill, pellet, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, gel, soft extract, extractum and membrane.
2, according to the compound formulation of notoginseng of the described treatment cardiovascular and cerebrovascular disease of claim 1, it is characterized in that: calculate according to components by weight percent, it is mainly by 20～80 parts of Radix Notoginseng, or corresponding the weight fraction Radix Notoginseng extract and 80～20 parts of the Radixs Astragali that obtain after extracting, or the Radix Astragali extract that corresponding weight fraction obtains after extraction is made.
3, according to the compound formulation of notoginseng of claim 1 or 2 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: calculate according to components by weight percent, it is by 50 parts of the Radixs Astragali, or 50 parts of the Radix Astragali extract that after extracting, obtains of corresponding weight fraction and Radix Notoginseng, or the Radix Notoginseng extract that corresponding weight fraction obtains after extracting is made described extract: Radix Notoginseng extract can be the highly finished product of Radix Notoginseng alcohol extract, pseudo-ginseng water extract, Radix Notoginseng water extract-alcohol precipitation extract, Radix Notoginseng semi-bionic extraction thing, Radix Notoginseng supercritical extract or above extract; Radix Astragali extract can be the highly finished product of (+)-Astragenol extract, Radix Astragali water extract, Radix Astragali water extract-alcohol precipitation extract, Radix Astragali semi-bionic extraction thing, Radix Astragali supercritical extract or above extract.
4, according to the compound formulation of notoginseng 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, gel, soft capsule, dispersible tablet.
5, as the preparation method of the compound formulation of notoginseng of any described treatment cardiovascular and cerebrovascular disease in the claim 1～4, it is characterized in that: take by weighing Radix Notoginseng, pulverize, alcohol reflux is collected extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, macroporous adsorbent resin is refining, drying gets Radix Notoginseng extract; Get the Radix Astragali, water boiling and extraction is filtered, and macroporous adsorbent resin is refining, and drying gets Radix Astragali extract; Make different preparations then respectively.
6, according to the preparation method of the compound formulation of notoginseng of the described treatment cardiovascular and cerebrovascular disease of claim 5, it is characterized in that: get and take by weighing Radix Notoginseng, pulverize, measure 80% alcohol reflux 3 times for 8 times, each 1 hour, collect extracting solution, filter, reclaim ethanol, get the Radix Notoginseng extracting solution, last D101 type macroporous adsorbent resin, 70% ethanol elution, the eluent concentrating under reduced pressure, vacuum drying gets Radix Notoginseng extract; Get the Radix Astragali, 8 times of water gagings decoct and extract 3 times, and each 1 hour, filter, AB-8 type macroporous adsorbent resin on the filtrate, 95% ethanol elution, the eluent water-bath volatilizes, concentrating under reduced pressure, vacuum drying gets Radix Astragali extract; Make different preparations then respectively.
7, according to the preparation method of the compound formulation of notoginseng of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Radix Notoginseng extract, Radix Astragali extract, add water for injection, and add 0.9% sodium chloride, stir evenly, cold preservation filters, filtrate adds 0.2% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 5.5～7.5, 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 formulation of notoginseng of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Radix Notoginseng extract, Radix Astragali extract adds water for injection, stirs evenly, cold preservation, filter, filtrate adds 0.2% active carbon, boils 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 5.5～7.5, by medicinal liquid: the ratio adding dextran of caffolding agent=2: 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 3 hours,-45 ℃ of pre-freezes began evacuation after 6 hours, and were warming up to-35 ℃, kept 3 hours; Be warming up to-30 ℃, kept 6 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to-10 ℃, kept 10 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 formulation of notoginseng of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Radix Notoginseng extract, Radix Astragali extract, add water for injection, stir evenly, cold preservation filters, filtrate adds 0.2% active carbon, boils 30 minutes, puts cold, be filtered to clear and bright, with 10%NaOH adjust pH 5.5～7.5, 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 formulation of notoginseng of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Radix Notoginseng extract, Radix Astragali extract, add water for injection, add 0.2% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 5.5～7.5, 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 ℃.
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| CN 200410040764 CN1634241A (en) | 2004-09-24 | 2004-09-24 | Compound formulation of notoginseng for treating cardiovascular and cerebrovascular diseases and its preparing process |
| CN 200510200552 CN1762401A (en) | 2004-09-24 | 2005-09-22 | Compound formulation of notoginseng for treating cardiovascular and cerebrovascular diseases, preparation method and application thereof |
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| CN 200410040764 CN1634241A (en) | 2004-09-24 | 2004-09-24 | Compound formulation of notoginseng for treating cardiovascular and cerebrovascular diseases and its preparing process |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457129C (en) * | 2005-08-15 | 2009-02-04 | 黑龙江省珍宝岛制药有限公司 | Preparation of Shuxiening injection, technique and adaptive disease |
| CN104147127A (en) * | 2014-07-25 | 2014-11-19 | 黑龙江中医药大学 | Traditional Chinese medicinal composition for treating malignant tumors, as well as preparation method and application thereof |
| CN108236677A (en) * | 2016-12-23 | 2018-07-03 | 北京济全生物科技有限公司 | A kind of Chinese medicine preparation and preparation method for treating cerebrovascular disease |
| CN114732848A (en) * | 2022-04-29 | 2022-07-12 | 浙江维康药业股份有限公司 | Application of traditional Chinese medicine composition in preparation of medicine for preventing and treating Alzheimer disease |
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2004
- 2004-09-24 CN CN 200410040764 patent/CN1634241A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457129C (en) * | 2005-08-15 | 2009-02-04 | 黑龙江省珍宝岛制药有限公司 | Preparation of Shuxiening injection, technique and adaptive disease |
| CN104147127A (en) * | 2014-07-25 | 2014-11-19 | 黑龙江中医药大学 | Traditional Chinese medicinal composition for treating malignant tumors, as well as preparation method and application thereof |
| CN104147127B (en) * | 2014-07-25 | 2019-09-27 | 黑龙江中医药大学 | A kind of Chinese medicine composition and its preparation method and application for treating malignant tumour |
| CN108236677A (en) * | 2016-12-23 | 2018-07-03 | 北京济全生物科技有限公司 | A kind of Chinese medicine preparation and preparation method for treating cerebrovascular disease |
| CN114732848A (en) * | 2022-04-29 | 2022-07-12 | 浙江维康药业股份有限公司 | Application of traditional Chinese medicine composition in preparation of medicine for preventing and treating Alzheimer disease |
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