CN1569160A - Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process - Google Patents
Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process Download PDFInfo
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Abstract
The invention provides a Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process, wherein the preparation is prepared from gen-seng and pseudo-ginseng with compatibility.
Description
Technical field: the present invention is a kind of Chinese medicine pharmaceutical 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, hypertension, cerebral infarction etc. all are one of the most common and diseases that harm is maximum in the world today, also be commonly encountered diseases, the frequently-occurring disease of harm China people ' s health, become human mortality's one of the main reasons; It was reported that sickness rate in recent years has and increases trend year by year, and in, young patient constantly increases.In order to reach the purpose of control, number of research projects has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; As: number of patent application is: 93108359, name is called " depressor and preparation method thereof ", number of patent application is: 02134144, name is called " Yixinkang table and preparation method thereof " and number of patent application is: 01803432, name is called " chemical compound (I), its extracting method and comprise the drug regimen of described chemical compound ".In these technology, first kind of product used Rhizoma Gastrodiae, and the side effect Compendium of Material Medica of Rhizoma Gastrodiae is just on the books: " obeying Rhizoma Gastrodiae for a long time; rubescent pellet all over " " Bencao Congxin " be cloud also: " if deficiency of the liver is at blood; disease sees that xerostomia just closes, and card persons such as the criminal's of reaching syndrome similar to wind disease cut and should not obey ", modern pharmacology proves that also it has the secondary work of certain poison, the untoward reaction report of clinical common anaphylactoid purpura; Second kind of product used Radix Polygoni Multiflori Preparata, and according to clinical report, the emodin in the Radix Polygoni Multiflori Preparata, chrysophanic acid have the side effect of hepatic injury; The third product is a monomeric compound, and curative effect is single, and the scope of application is little, the effect instability.In view of such circumstances, seek that a kind of medical material 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 Chinese medicine pharmaceutical 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, hypertension, cerebral infarction etc. all contract because of blood vessel is narrow, reason such as blood flow minimizing causes the diseases induced principle of blood supply insufficiency to carry out the prescription of medicine; Personnel selection participates in Radix Notoginseng and carries out prescription, preparation; The Radix Ginseng of selecting for use among the present invention has strongly invigorating primordial QI, and multiple arteries and veins takes off admittedly, invigorating the spleen to benefit the lung, the effect of promoting the production of body fluid, calming the nerves, and pharmacological research shows: but Radix Ginseng human body immunity improving power strengthens premunition, regulates the human body cholesterol metabolism, suppresses the generation of hypercholesterolemia blood disorder; In addition, also can strengthen cardiac contractile force, excited people's nervous function, hemopoietic function etc.; The Radix Notoginseng blood stasis dispelling of selecting for use is promoted blood circulation, and invigorates blood circulation and nourishes heart; Pharmacological research shows: Radix Notoginseng has obvious coronary artery dilator, increase the effect of coronary flow, and can reduce myocardial oxygen consumption, and strengthen the hypoxia-bearing capability of cardiac muscle, therefore the preparation that adopts Radix Ginseng and Radix Notoginseng compatibility to make 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 has curative effect preferably for treating cardiovascular and cerebrovascular disease such as coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis, hyperlipidemia etc.And the present invention is pure Chinese medicinal preparation, but the little patients life-time service of its untoward reaction.The present invention also can be used for hepatopathy, antitumor, alzheimer disease, the nephrotic syndrome, diabetes etc.
The present invention constitutes like this: calculate according to components by weight percent, the Radix Ginseng extract that it is mainly obtained after extracting by 1～99 part of Radix Ginseng or corresponding weight portion, the Radix Notoginseng extract that obtains after extracting with 99～1 parts of Radix Notoginseng or corresponding weight portion is made into injection, comprises: injection, powder pin, freeze-dried powder, tablet, capsule, soft capsule, pellet, granule, pill, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, gel, soft extract, extractum and membrane.Say accurately, the Radix Ginseng extract that it is mainly obtained after extracting by 20～80 parts of Radix Ginsengs or corresponding weight portion, the Radix Notoginseng extract that obtains after extracting with 80～20 parts of Radix Notoginseng or corresponding weight portion is made.The Radix Ginseng extract that optimizing prescriptions is obtained after extracting by 50 parts of Radix Ginsengs or corresponding weight portion, the Radix Notoginseng extract that obtains after extracting with 50 parts of Radix Notoginseng or corresponding weight portion is made.Preparation of the present invention is: injection, comprising: injection, powder pin, freeze-dried powder, tablet, capsule, granule, drop pill, gel, pellet, soft capsule, dispersible tablet.Preparation method of the present invention: it is an amount of to get Radix Ginseng, pulverizes, and alcohol reflux is collected extracting solution, filter, and concentrating under reduced pressure, decompression recycling ethanol is re-refined, is concentrated, and crushed after being dried promptly gets Radix Ginseng extract; Get Radix Notoginseng, pulverize, alcohol reflux is collected extracting solution, reclaims ethanol, re-refine, concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, make different preparations then respectively; Perhaps get Radix Ginseng, Radix Notoginseng is an amount of, pulverizes, alcohol reflux is collected extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol is re-refined, is concentrated, crushed after being dried is made different preparations then respectively.Say accurately, take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 20%～70% alcohol reflux 1～5 time, each 1～5h, collection extracting solution with 2～15 times, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, with 30%～90% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, different preparations is made in concentrated, dry, pulverizing then respectively.
Injection in the preparation of the present invention prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h collects extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent concentrates through decompression recycling ethanol, dry, pulverize, add the dissolving of injection water, regulate pH value to 6.5～7.0 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled, filter, add an amount of sodium chloride for injection and make it dissolving; Add water for injection again to certain volume, filtration, fill, sterilization, promptly.
Injection in the preparation of the present invention prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h collects extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent concentrates through decompression recycling ethanol, dry, pulverize, add the dissolving of injection water, regulate pH value to 6.5～7.0 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled, filter, add an amount of sodium chloride for injection and make it dissolving; Add sterile water for injection to full dose, vacuum lyophilization or aseptic filtration or spray drying or in organic solvent recrystallization, packing, the sealing promptly.
The dispersible tablet of preparation of the present invention prepares like this: take by weighing Radix Ginseng, Radix Notoginseng is ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measures 40% alcohol reflux 3 times for 12 times, each 2h collects extracting solution, filters, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent concentrates through decompression recycling ethanol, dry, pulverize, add 5% carboxymethyl starch sodium, 1.0% sodium lauryl sulphate, mixing, 95% ethanol is moistening, granulates, dry, granulate adds 1.0% carboxymethyl starch sodium, mixing, tabletting, promptly.
The soft capsule of preparation of the present invention prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrated, dry, pulverizing, extract powder and triglyceride were mixed into medicinal liquid with 1: 40, and the softgel shell prescription is gelatin: glycerol: water=10: 2: 13, pill, promptly.
The pellet of preparation of the present invention prepares like this: take by weighing Radix Ginseng; Radix Notoginseng; be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m; measure 40% alcohol reflux 3 times for 12 times; each 2h collects extracting solution, filters; concentrating under reduced pressure; decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution; collect effluent to colourless; effluent concentrates through decompression recycling ethanol; dry; pulverize, add 22.5% starch; 2.0% pregelatinized Starch; 15.0% microcrystalline Cellulose; 1.0% magnesium stearate; add in the mixer granulator; add concentration 2%HPMC solution and granulate, drying, promptly.
Tablet in the preparation of the present invention prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h collects extracting solution, filters, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, and concentrated, dry, pulverizing add 5% lactose, 3% low-substituted hydroxypropyl cellulose, adding the moistening back of 50% ethanol granulates, drying, tabletting, promptly.
Granule in the preparation of the present invention prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h collects extracting solution, filters, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, and concentrated, dry, pulverizing add 5% lactose, adding the moistening back of 50% ethanol granulates, make granule, drying, promptly.
Compared with prior art, Radix Ginseng has strongly invigorating primordial QI among the present invention, and multiple arteries and veins takes off admittedly, invigorating the spleen to benefit the lung, the effect of promoting the production of body fluid, calming the nerves, pharmacological research shows: but Radix Ginseng human body immunity improving power strengthens premunition, regulate the human body cholesterol metabolism, suppress the generation of hypercholesterolemia blood disorder.In addition, also can strengthen cardiac contractile force, excited people's nervous function, hemopoietic function etc.; The Radix Notoginseng blood stasis dispelling is promoted blood circulation, and invigorates blood circulation and nourishes heart, and pharmacological research shows: Radix Notoginseng has obvious coronary artery dilator, increases the effect of coronary flow, and can reduce myocardial oxygen consumption, strengthens the hypoxia-bearing capability of cardiac muscle, therefore adopts Radix Ginseng and Radix Notoginseng compatibility to make preparation; Have activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, improve blood circulation and metabolic effect.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 has curative effect preferably for treating cardiovascular and cerebrovascular disease such as coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis, hyperlipidemia etc.And not selecting Rhizoma Gastrodiae, the Radix Polygoni Multiflori Preparata of side effect for use, the present invention is a pure Chinese medicinal preparation, but the little patients life-time service of its untoward reaction.
In preparation method provided by the invention, Radix Ginseng, Radix Notoginseng have been adopted superfine communication technique, the plant cell wall breaking rate is reached more than 90%, and effective ingredient fully exposes in the cell, has shortened extraction time and has improved extraction ratio, can reduce the raw material consumption, the reducing of grinding particle size can be accelerated medicine dissolving, infiltration rate in vivo, improves bioavailability, increases drug effect, this product can improve the product curative effect after adopting superfine communication technique; Simultaneously the applicant is determined by experiment the suitable pH value of injection, has guaranteed the stable of Radix Ginseng, compound components of panax notoginseng saponin, and the invention 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: disintegrating process screening
Test 1 group: preparation group of the present invention: Radix Ginseng, Radix Notoginseng are made the granule of making behind the micropowder (after Radix Notoginseng smashs to pieces, pulverize through super micron mill, drop temperature is 35 ℃～40 ℃);
Test 2 groups: the common flour group: after Radix Ginseng, Radix Notoginseng are smashed to pieces, after pulverizer is pulverized, cross the granule of making behind 100 mesh sieves;
8 rabbit fasting 24h, 2 is the blank group, irritates stomach with normal saline; 3 are 2 groups of experiments, irritate stomach; 3 are 1 group of experiment, irritate stomach.Before irritating stomach every day, experimental group faces the suspension that is made into 11.75gL-1, with 0.18mgg
-1Dosage irritate stomach, administration every day 3 times, each 6h at interval, administration one day.The last time after the administration 7,8,9,10, the 11h 5mL that takes a blood sample is after blood sample is placed 3h, with the centrifugal 15min (4000rmin of centrifuge
-1).The accurate serum 2mL that draws adds 3mL methanol mixing, puts 37 ℃ of extraction 1h in the constant temperature jolting extractor, takes out centrifugal 15min (4000rmin
-1), get supernatant and be settled in the 5mL measuring bottle, through filtering with microporous membrane, get 20.0 μ L sample introductions and measure.
Ginsenoside Rb in the serum behind the administration 10h
1, Rg
1, the relative peak area of Re (100%)
Group n dosage (mgg
-1) relative peak area (100%)
Rb
1 Rg
1 Re
Normal saline 2
Test 1 group 3 0.18 0.114 0.236 0.381
Test 2 group 3 0.18 0.038 0.072 0.082
Show that by experimental result the disintegrating process that the present invention adopts makes that product absorbs in the rabbit body faster than conventional method, and absorbtivity is big.
Experimental example 2: extraction process screening
Modern pharmacological research proves: the ginsenoside is the labeled component and the active component of Radix Ginseng; Radix Notoginseng total arasaponins is the anginal main component of Radix Notoginseng resisting coronary heart disease, is one of onset composition of this product, and extraction process directly influences the curative effect and the quality of product.
1. Different Extraction Method is to the influence of total saponins extraction ratio
Method decocting method warm macerating method ethanol refluxing process microwave method ultrasonic method semi-biomimetic method supercritical extraction
Extraction ratio % 81.2 80.3 84.6 79.9 80.1 80.2 81.3
2. different influences of extracting solvent to total saponin content
Solvent 10% ethanol 20% ethanol 40% ethanol 60% ethanol 70% ethanol 90% ethanol
Content % 1.03 3.55 4.39 3.48 3.37 2.11
The result shows: extraction process of the present invention is rationally feasible, the effective component extraction rate height.
The screening of experimental example 3 process for refining
1. different purification process are to the influence of total saponins purity (total saponins/extractum)
Method n-butanol extraction chloroform extraction macroporous adsorbent resin
Purity % 55% 51% 72%
2. the selection of eluent determining alcohol
Determining alcohol % dry extract amount mg saponin amount mg accounts for saponin extracted amount % in the total saponins percentage ratio % extractum
20 159.2 61.4 12.9 38.5
30 130.5 90.6 19.0 69.4
60 420.6 286.6 60.2 68.1
70 720.4 438.6 92.0 64.9
90 36.1 16.0 3.3 44.3
The screening of experimental example 4 moulding processs
Moulding process is directly connected to the character and the absorption in vivo utilization of product, is key technology of the present invention.
The percentile mensuration of moisture absorption: get a certain amount of extract powder, put constant weight 48h in the phosphorus pentoxide desiccator.The glass exsiccator that the bottom is filled the sodium chloride supersaturated solution is put into 25 ℃ constant incubator constant temperature 24h, and the interior relative humidity of exsiccator this moment is 75%.Put into the medicated powder of thick about 2mm in the weighing botle bottom of constant weight, accurately weigh and be placed on above-mentioned glass exsiccator interior (the weighing bottle cap is opened) in 25 ℃ of preservations, regularly (6,12,24,48,60h) weighing, be calculated as follows the moisture absorption percentage rate, and be vertical coordinate with the moisture absorption percentage rate, the time (h) is the abscissa mapping.
Hydroscopicity (%)=(medicated powder weight after the moisture absorption-moisture absorption prodrug grain weight amount)/moisture absorption prodrug grain weight amount * 100%
Average disintegration time: adopting changes the basket method, and lift disintegration tester, tablet or capsule are got 6 units, calculates the meansigma methods of passing through the screen cloth time fully.
(1) granule
1. it is an amount of to get extract powder, respectively with soluble starch, lactose and dextrin mixing, gets in right amount and measures by above-mentioned extract powder moisture absorption percentage rate assay method.
The moisture absorption percentage rate of different proportioning mixture
Extract powder and adjuvant supplementary product consumption time t/h
6 12 24 48 60
Extract powder 5% 8.16 12.54 16.48 18.96
19.62
Extract powder+soluble starch 5% 8.06 11.95 16.40 18.62
19.01
Extract powder+lactose 5% 6.71 9.82 13.23 15.65
16.48
Extract powder+dextrin 5% 7.88 12.01 15.13 17.34
17.25
2. the lactose consumption is to the hygroscopic influence of extract powder
Lactose consumption time t/h
6 12 24 48 60
2％ 7.08 10.19 13.78 16.25 17.06
3％ 6.96 9.89 13.65 15.75 16.81
5％ 6.70 9.79 13.18 15.45 16.46
(2) tablet
1. prescription design
Supplementary material prescription 1 prescription 2 prescriptions 3 prescriptions 4 prescriptions 5 prescriptions
6
Extract powder (kg) 0.4 0.4 0.4 0.4 0.4 0.4
Soluble starch 0.3%
Lactose 5% 5% 5%
Dextrin 5%
Low-substituted hydroxypropyl cellulose 5%
Carboxymethyl starch sodium 5%
Magnesium stearate 0.5% 0.5%
0.5％
1. disintegration (min) seen in the extra of writing out a prescription
1 loose, and pit 28 is arranged
2 hardness are good, and bright and clean 40
3 hardness are good, glossy degree 30
4 hardness are good, glossy degree 45
5 hardness are good, and mottle 45 is arranged
6 is easily crisp broken, and mottle 50 is arranged
2. the low-substituted hydroxypropyl cellulose consumption is to EFFECT OF CORK STOPPER (n=3)
Carboxymethyl starch sodium consumption (%) 13579
Disintegration (min) 42 20 29 30 35
The result shows, adopts the selected prepared quality of the pharmaceutical preparations of adjuvant of the present invention stable, controlled; Make that the formed product of gained of the present invention is good.
(3) selection of injection pH value: the applicant finds that in development product of the present invention contains a large amount of saponin, because of facile hydrolysis causes the medicine instability, its drug effect reduces, suitable acid-base value is the stable key factor of medicine, and in order to improve the quality of this injection, the applicant has carried out a large amount of experiments.
1. the selection of injection pH value: 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 5.5 differ from 1.52
6.0 clear and bright 1.50 clear and bright 1.14
6.5 clear and bright 1.43 clear and bright 1.32
7.0 clear and bright 1.49 differ from 1.41
Differ from 1.08 7.5 differ from 1.55
Differ from 1.01 8.0 differ from 1.57
2. the selection of powder pin pH value:
PH value clarity mouldability
5.5 difference is not good enough
6.0 difference molding
6.5 clear and bright molding
7.0 clear and bright molding
7.5 difference is not good enough
8.0 difference is not good enough
(4) soft capsule: the stability of glue shell formulation and technology plays decisive role to the quality of soft capsule, and all variations of its quality are relevant with glue shell formulation and technology as disintegration, oxidation, variable color etc.Therefore, seek best glue shell formulation and technology, very crucial to ensuring the quality of products.This product extract powder and triglyceride were mixed into medicinal liquid with 1: 40, made soft capsule again.The soft capsule that makes was placed 5 months, observed its softgel shell cosmetic variation, and measure its disintegration.The mensuration of disintegration time: adopting changes the basket method, and lift disintegration tester, tablet or capsule are got 6 units, calculates the meansigma methods of passing through the screen cloth time fully.
Prescription kind ratio softgel shell disintegration outward appearance
10: 2: 13 7.5min roundings of 1 gelatin, glycerol, water, smooth, invariant color
2 gelatin, glycerol, water 17.8min hardening in 15: 1: 11, variable color
3 gelatin, glycerol 11.5min rounding, smooth, hardening slightly in 10: 2
4 gelatin, water 25.6min hardening in 10: 11, variable color
5 gelatin 36.1min hardening, variable color
The result shows that the present invention chooses the softgel shell prescription and is gelatin: glycerol: water=10: 2: 13, and functional.
(5) dispersible tablet: dispersible tablet can be in water disintegrate rapidly, form uniform suspension, make things convenient for the patient of old people, child and dysphagia to take.And the dispersible tablet disintegrate is fast, and the medicine stripping is fast, can improve bioavailability.Dispersible tablet requires disintegrate in the 3min, and disintegrating agent is particularly important in the selection of prescription.Pass through prescription screening, the good product quality that makes at principal agent and supplementary product consumption the applicant.
1. prescription CMS-Na (in add) % CMS-Na (adding) % SDS% disintegration time (min)
1 4 1.0 0.5 2.64
2 4 2.0 1.5 1.71
3 5 1.0 1.0 0.72
4 5 2.0 0.5 1.17
5 6 1.0 1.5 0.94
6 6 2.0 1.0 0.93
The result shows, optimizing prescriptions is 5%CMS-Na (in add), 1.0%CMS-Na (adding), 1.0%SDS.
CMS-Na is a carboxymethyl starch sodium, and SDS is a sodium lauryl sulphate.
(6) micropill: take by weighing this product dry extract and each adjuvant by prescription; add in the mixer granulator; high-speed stirred 3min; add binding agent 2%HPMC solution in right amount to the granulation state, start high-speed stirred and granulation motor simultaneously, close the granulation motor behind about 30min; continue high-speed stirred 10min; discharging is put baking oven in dry below 60 ℃
Prescription is preferred: starch X1, pregelatinized Starch X2, microcrystalline Cellulose X3, Icing Sugar X4, magnesium stearate X5, determined 6 levels (promptly accounting for total powder weight percentage ratio) at the zone of reasonableness of each adjuvant simultaneously.
Every batch of product is estimated from roundness (Y1), surface smoothness (Y2), one-tenth ball rate (Y3), ball footpath (Y4), five aspects of homogeneity (Y5), ball footpath of micropill.Each index all batch between beat relatively branch, two of Y1, Y5 give a mark in 1～10 scope by visual method; Y2 presses visual method marking because the differences between batches amplitude is less in 1～5 scope; Y3 serves as according to marking with the yield of 40～14 orders size micropill; Y4 then selects 24～18 orders size to be best ball footpath, according to the micropill yield marking of this scope.
Prescription X1 (%) X2 (%) X3 (%) X4 (%) X5 (%)
1 23 - 7.2 15.0 1.2
2 - 7.0 11.6 5.0 0.5
3 22.5 2.0 15.0 - 1.0
4 30.0 10.0 - 6.0 0.9
5 36.5 12.0 8.4 12.5 1.2
6 40.0 8.0 12.8 7.2 -
Prescription Y1 Y2 Y3 Y4 Y5 ∑ y
1 2.0 1.5 5.0 7.0 5.0 20.5
2 2.5 2.0 6.5 5.6 5.4 22.0
3 8.0 4.0 12.0 9.0 10.0 43.0
4 6.0 2.5 7.0 4.0 3.0 22.5
5 7.0 6.5 9.0 2.5 7.0 32.0
6 1.0 0.5 1.5 1.0 1.0 5.0
The result shows that No. 3 is best prescription: starch 22.5%, pregelatinized Starch 2.0%, microcrystalline Cellulose 15.0%, magnesium stearate 1.0%.
Experimental example 5: to the influence of stasis syndrome rat blood rheological characteristic
Test 1 group: Yixinkang table (Radix Ginseng, Radix Polygoni Multiflori Preparata, Radix Notoginseng, Fructus Crataegi);
Test 2 groups: tablet group of the present invention
60 of rats, male and female half and half, body weight 270 ± 25g.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 dosage (g/kg) whole blood viscosity plasma viscosity packed cell volume reduced viscosity aggregate index deformation index
Height hits to hang down and cuts
Normal control-5.33 ± 1.13 7.88 ± 1.52 14.71 ± 1.51 1.52 ± 0.12 0.43 ± 0.02 7.67 ± 1.98 8.13 ± 1.52 0.82 ± 0.08
Model contrast-6.85 ± 1.74 8.65 ± 1.95 16.73 ± 1.46 2.13 ± 0.14 0.50 ± 0.06 8.56 ± 2.51 9.12 ± 1.54 0.68 ± 0.15
Test 1 group 6.0 5.87 ± 0.59 8.01 ± 1.05 14.84 ± 1.74 1.78 ± 0.19 0.45 ± 0.13 7.76 ± 1.23 8.30 ± 1.23 0.74 ± 0.17
Test 2 group 6.0 5.62 ± 1.01 7.82 ± 0.70 14.79 ± 1.70 1.71 ± 0.22 0.44 ± 0.06 7.69 ± 3.22 8.25 ± 2.09 0.76 ± 0.09
The result shows, preparation good effect of the present invention, and do not select Radix Polygoni Multiflori Preparata for use, do not have its untoward reaction that brings and anaphylaxis.
Experimental example 6: to the influence of rat prothrombin time (PT) thrombin clotting time (TT) slurry recalcification time
50 of SD rats, body weight 285 ± 15g, male and female half and half, one week of successive administration.1h pentobarbital sodium anesthesia back femoral vein is got blood after the last administration, decides prothrombin time (PT) hemase setting time (TT) slurry recalcification time.
Group agent (g/kg) PT (min) TT (min) clotting time (s)
Blank-10.61 ± 0.95 16.83 ± 2.70 185.8 ± 29.0
Radix Ginseng 2.0 15.25 ± 0.81 21.30 ± 2.43 103.0 ± 21.7
6.0 17.12±2.10 24.25±1.95 133.7±23.2
Radix Notoginseng 2.0 14.13 ± 0.24 19.72 ± 1.35 123.1 ± 25.3
6.0 20.00±2.77 26.75±0.87 203.1±36.3
Panax pseudoginseng 2.0 16.14 ± 0.24 22.52 ± 1.35 101.1 ± 25.4
6.0 22.00±2.77 28.88±0.87 123.1±36.5
The result shows that the curative effect of Panax pseudoginseng prescription is better than Radix Ginseng, the independent medication of Radix Notoginseng, and both share, have the effect of Synergistic.
Experimental example 7: preparation of the present invention is to the influence of blood stasis model rabbit blood rheological characteristic
36 of rabbit are divided into 4 groups at random, and 9 every group, ♀ ♂ half and half is respectively blank group, model control group, positive drug control group and experimental 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, the injection of the present invention (being made into) of experimental group injection 0.25mg/ml with NF, 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
Experimental group 0.25 2.32 ± 0.56 14.79 ± 3.59 2.59 ± 0.87
The result shows, preparation good effect of the present invention.
Experimental example 8: the anti-law during ischemia Study on Damage of preparation of the present invention
Animal and grouping adult healthy male rat, body weight 240～360g, is divided into 10 of Sham-operated control group with laboratory animal, 15 of ischemia-reperfusion group, 15 of treatment groups at random by totally 40.
Experimental technique: 12h fasting before the art, can freely drink water, art places operating room preceding half an hour.The operating room temperature is about 25 ℃.1.4% defends barbital sodium 40mg/kg intraperitoneal injection of anesthesia, aseptic condition is done to go up median abdominal incision down and is gone into abdomen, appears the hepatic portal structure, blocks hepatic portal structures such as Hepatic artery, portal vein, common bile duct 30min altogether with the pekinese pincers, open then hepatic portal is put to death animal behind the 90min.After the Animal Anesthesia from the vena dorsalis penis infusion liquid, ischemia-reperfusion group and Sham-operated control group are normal saline 1ml/kg, the treatment group is injection 1ml/kg of the present invention, Sham-operated control group is not made hepatic portal occlusion, get hepatic tissue and survey malonaldehyde, superoxide dismutase after liver is poured into 90min again, 1ml surveys glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, GOT, lactic dehydrogenase isoenzyme from the postcava blood sampling.
Test item and method: superoxide dismutase activity is pressed xanthine oxidase and is measured, and malonaldehyde clings to appropriate acid (TBA) method by sulfo-and measures, and presses performance rate method with automatic clinical chemistry analyzer and measures glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, GOT, lactic dehydrogenase isoenzyme
Each organizes the content (x ± s) of rat malonaldehyde, superoxide dismutase, glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, GOT, lactic dehydrogenase isoenzyme
Sham-operated control group ischemia-reperfusion group treatment group
Glutamate pyruvate transaminase (u/l) 113 ± 29 2729 ± 183 2114 ± 156
Glutamic oxaloacetic transaminase, GOT (u/l) 231 ± 45 2990 ± 85 2054 ± 123
Lactic dehydrogenase isoenzyme (u/l) 248 ± 38 5904 ± 731 3872 ± 564
Malonaldehyde (nmol/mg) 0.88 ± 0.08 1048 ± 0.12 1.24 ± 0.41
Superoxide dismutase (u/mg) 26.15 ± 0.97 10.94 ± 0.88 17.13 ± 0.53
When rat liver pours into 90min again, the hepatic tissue malonaldehyde of ischemia-reperfusion group and treatment group generates, superoxide dismutase consumption, the lift-off value of serum glutamic pyruvic transminase, glutamic oxaloacetic transaminase, GOT, lactic dehydrogenase isoenzyme is all more than Sham-operated control group, and ischemia-reperfusion group or treatment group are compared with Sham-operated control group, and all there were significant differences.The hepatic tissue malonaldehyde of ischemia-reperfusion group generates, superoxide dismutase consumption, and the lift-off value of serum glutamic pyruvic transminase, glutamic oxaloacetic transaminase, GOT, lactic dehydrogenase isoenzyme is all more than the treatment group, and preparation of the present invention has the effect of anti-law during ischemia damage.
Concrete embodiment:
Embodiments of the invention 1: take by weighing Radix Ginseng 990g, Radix Notoginseng 10g, pulverize, 2 times of amount 20% alcohol reflux 1h collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 30% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, and concentrated, dry, pulverizing add 5% lactose, 3% low-substituted hydroxypropyl cellulose, add the moistening back of 50% ethanol and granulate drying, tabletting, promptly get tablet, each 2, every day 3 times.
Embodiments of the invention 2: take by weighing Radix Ginseng 10g, Radix Notoginseng 990g, be ground into micropowder (particle diameter distributes less than 30 μ m more than 99%), measure 70% alcohol reflux 5 times for 15 times, each 5h collects extracting solution, filters, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 90% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrated, dry, pulverizing add 5% lactose, add the moistening back of 50% ethanol and granulate, make granule, drying promptly gets granule.
Embodiments of the invention 3: take by weighing Radix Ginseng 500g, Radix Notoginseng 500g, be ground into 12 times of amounts of micropowder, 40% alcohol reflux 3 times, each 2h, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrate, dry, pulverize, add the dissolving of injection water, regulate pH value to 6.5～7.5 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled filters, and adds an amount of sodium chloride for injection and makes it dissolving; Add water for injection again to certain volume, filtration, fill, sterilization promptly get injection.
Embodiments of the invention 4: take by weighing Radix Ginseng 800g, Radix Notoginseng 200g, be ground into micropowder (particle diameter distributes less than 30 μ m more than 99%), measure 40% alcohol reflux 3 times for 12 times, each 2h collects extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent concentrates through decompression recycling ethanol, dry, pulverize, add the dissolving of injection water, regulate pH value to 6.5～7.5 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled, filter, add an amount of sodium chloride for injection and make it dissolving; Add sterile water for injection to full dose, vacuum lyophilization or aseptic filtration or spray drying or in organic solvent recrystallization, packing, sealing promptly gets injection.
Embodiments of the invention 5: take by weighing Radix Ginseng 200g, Radix Notoginseng 800g, be ground into micropowder (particle diameter distributes less than 30 μ m more than 99%), measure 70% alcohol reflux 5 times for 15 times, each 5h collects extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 90% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrate, dry, pulverize, add 5% lactose, add the moistening back of 50% ethanol and granulate, make granule, drying, encapsulated, promptly get capsule.
Embodiments of the invention 6: take by weighing Radix Ginseng 800g, Radix Notoginseng 200g takes by weighing Radix Ginseng, Radix Notoginseng is ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h collects extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrate, dry, pulverize, add 5% carboxymethyl starch sodium, 1.0% sodium lauryl sulphate, mixing, 95% ethanol is moistening, granulate drying, granulate, add 1.0% carboxymethyl starch sodium, mixing, tabletting promptly gets dispersible tablet.
Embodiments of the invention 7: take by weighing Radix Ginseng 200g, Radix Notoginseng 800g, take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h collects extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent concentrates through decompression recycling ethanol, dry, pulverize, extract powder and triglyceride to be mixed into medicinal liquid at 1: 40, the softgel shell prescription is gelatin: glycerol: water=10: 2: 13, pill promptly gets soft capsule.
Embodiments of the invention 8: take by weighing Radix Ginseng 500g; Radix Notoginseng 500g; take by weighing Radix Ginseng; Radix Notoginseng; be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measures 40% alcohol reflux 3 times for 12 times, each 2h; collect extracting solution; filter concentrating under reduced pressure, decompression recycling ethanol; refining with macroporous adsorbent resin; use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol; concentrate; dry; pulverize; add 22.5% starch; 2.0% pregelatinized Starch; 15.0% microcrystalline Cellulose; 1.0% magnesium stearate adds in the mixer granulator, adds concentration 2%HPMC solution and granulates; drying promptly gets pellet.
Claims (13)
1, a kind of Chinese medicine pharmaceutical preparation for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, the Radix Ginseng extract that it is mainly obtained after extracting by 1～99 part of Radix Ginseng or corresponding weight portion, the Radix Notoginseng extract that obtains after extracting with 99～1 parts of Radix Notoginseng or corresponding weight portion is made into injection, comprise: injection, the powder pin, freeze-dried powder, tablet, capsule, soft capsule, pellet, granule, pill, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, gel, soft extract, extractum and membrane.
2, according to the Chinese medicine pharmaceutical preparation of the described treatment cardiovascular and cerebrovascular disease of claim 1, it is characterized in that: calculate according to components by weight percent, the Radix Ginseng extract that it is mainly obtained after extracting by 20～80 parts of Radix Ginsengs or corresponding weight portion, the Radix Notoginseng extract that obtains after extracting with 80～20 parts of Radix Notoginseng or corresponding weight portion is made.
3, according to the Chinese medicine pharmaceutical preparation of claim 1 or 2 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: calculate according to components by weight percent, the Radix Ginseng extract that it is mainly obtained after extracting by 50 parts of Radix Ginsengs or corresponding weight portion, the Radix Notoginseng extract that obtains after extracting with 50 parts of Radix Notoginseng or corresponding weight portion is made.
4, according to the Chinese medicine pharmaceutical 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, gel, pellet, soft capsule, dispersible tablet.
5, as the preparation method of the Chinese medicine pharmaceutical preparation of the described treatment cardiovascular and cerebrovascular disease of claim 1-4, it is characterized in that: it is an amount of to get Radix Ginseng, pulverizes alcohol reflux, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, re-refine, concentrate, crushed after being dried promptly gets Radix Ginseng extract; Get Radix Notoginseng, pulverize, alcohol reflux is collected extracting solution, reclaims ethanol, re-refine, concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, make different preparations then respectively; Perhaps get Radix Ginseng, Radix Notoginseng is an amount of, pulverizes, alcohol reflux is collected extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol is re-refined, is concentrated, crushed after being dried is made different preparations then respectively.
6, according to the preparation method of the Chinese medicine pharmaceutical preparation of the described treatment cardiovascular and cerebrovascular disease of claim 5, it is characterized in that: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 20%～70% alcohol reflux 1～5 time with 2～15 times, each 1～5h, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, with 30%～90% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, different preparations is made in concentrated, dry, pulverizing then respectively.
7, preparation method according to the Chinese medicine pharmaceutical preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the injection in the described preparation prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrate, dry, pulverize, add the dissolving of injection water, regulate pH value to 6.5～7.0 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled filters, and adds an amount of sodium chloride for injection and makes it dissolving; Add water for injection again to certain volume, filtration, fill, sterilization, promptly.
8, preparation method according to the Chinese medicine pharmaceutical preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the injection in the described preparation prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrate, dry, pulverize, add the dissolving of injection water, regulate pH value to 6.5～7.0 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled filters, and adds an amount of sodium chloride for injection and makes it dissolving; Add sterile water for injection to full dose, vacuum lyophilization or aseptic filtration or spray drying or in organic solvent recrystallization, packing, the sealing promptly.
9, preparation method according to the Chinese medicine pharmaceutical preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the dispersible tablet of described preparation prepares like this: take by weighing Radix Ginseng, Radix Notoginseng is ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measures 40% alcohol reflux 3 times for 12 times, each 2h, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrate, dry, pulverize, add 5% carboxymethyl starch sodium, 1.0% sodium lauryl sulphate, mixing, 95% ethanol is moistening, granulate drying, granulate, add 1.0% carboxymethyl starch sodium, mixing, tabletting, promptly.
10, preparation method according to the Chinese medicine pharmaceutical preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the soft capsule of described preparation prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measure 40% alcohol reflux 3 times for 12 times, each 2h, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent concentrates through decompression recycling ethanol, dry, pulverize, extract powder and triglyceride to be mixed into medicinal liquid at 1: 40, the softgel shell prescription is gelatin: glycerol: water=10: 2: 13, and pill, promptly.
11; preparation method according to the Chinese medicine pharmaceutical preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases; it is characterized in that: the pellet of described preparation prepares like this: take by weighing Radix Ginseng; Radix Notoginseng; be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m; measure 40% alcohol reflux 3 times for 12 times; each 2h; collect extracting solution; filter concentrating under reduced pressure, decompression recycling ethanol; refining with macroporous adsorbent resin; use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol; concentrate; dry; pulverize; add 22.5% starch; 2.0% pregelatinized Starch; 15.0% microcrystalline Cellulose; 1.0% magnesium stearate adds in the mixer granulator, adds concentration 2%HPMC solution and granulates; drying, promptly.
12, preparation method according to the Chinese medicine pharmaceutical preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the tablet in the described preparation prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measures 40% alcohol reflux 3 times for 12 times, each 2h, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrate, dry, pulverize, add 5% lactose, 3% low-substituted hydroxypropyl cellulose adds the moistening back of 50% ethanol and granulates drying, tabletting, promptly.
13, preparation method according to the Chinese medicine pharmaceutical preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the granule in the described preparation prepares like this: take by weighing Radix Ginseng, Radix Notoginseng, be ground into micropowder: particle diameter distributes more than 99% less than 30 μ m, measures 40% alcohol reflux 3 times for 12 times, each 2h, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, refining with macroporous adsorbent resin, use 60% ethanol elution, collect effluent to colourless, effluent is through decompression recycling ethanol, concentrate, dry, pulverize, add 5% lactose, add the moistening back of 50% ethanol and granulate, make granule, drying, promptly.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103070897A (en) * | 2011-10-26 | 2013-05-01 | 澳门科技大学 | Traditional Chinese medicine composition used for treating coronary heart disease, and preparation method thereof |
| CN104758353A (en) * | 2014-12-31 | 2015-07-08 | 四川新绿色药业科技发展股份有限公司 | Medicine composition for treating cardiovascular diseases, preparation method and application thereof |
| CN104784236A (en) * | 2015-04-30 | 2015-07-22 | 广西梧州三鹤药业有限公司 | Traditional Chinese medicine composition for preventing cardiovascnlar and cerebrovascular diseases |
| CN105055851A (en) * | 2015-08-03 | 2015-11-18 | 河北科技大学 | Chinese medicinal composition for treatment of diabetes, preparation and application thereof |
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2004
- 2004-05-10 CN CN 200410022512 patent/CN1569160A/en active Pending
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103070897A (en) * | 2011-10-26 | 2013-05-01 | 澳门科技大学 | Traditional Chinese medicine composition used for treating coronary heart disease, and preparation method thereof |
| CN104758353A (en) * | 2014-12-31 | 2015-07-08 | 四川新绿色药业科技发展股份有限公司 | Medicine composition for treating cardiovascular diseases, preparation method and application thereof |
| CN104758353B (en) * | 2014-12-31 | 2018-08-03 | 四川新绿色药业科技发展有限公司 | A kind of pharmaceutical composition and its preparation method and application for treating angiocardiopathy |
| CN104784236A (en) * | 2015-04-30 | 2015-07-22 | 广西梧州三鹤药业有限公司 | Traditional Chinese medicine composition for preventing cardiovascnlar and cerebrovascular diseases |
| CN105055851A (en) * | 2015-08-03 | 2015-11-18 | 河北科技大学 | Chinese medicinal composition for treatment of diabetes, preparation and application thereof |
| CN105055851B (en) * | 2015-08-03 | 2019-07-19 | 河北科技大学 | A kind of Chinese medicine composition that treating diabetes, its preparation and its application |
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