CN1569159A - 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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- CN1569159A CN1569159A CN 200410022511 CN200410022511A CN1569159A CN 1569159 A CN1569159 A CN 1569159A CN 200410022511 CN200410022511 CN 200410022511 CN 200410022511 A CN200410022511 A CN 200410022511A CN 1569159 A CN1569159 A CN 1569159A
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- radix ginseng
- ethanol
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- RGHFKWPGWBFQLN-UHFFFAOYSA-M sodium;5,5-diethylpyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].CCC1(CC)C([O-])=NC(=O)NC1=O RGHFKWPGWBFQLN-UHFFFAOYSA-M 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 210000001260 vocal cord Anatomy 0.000 description 1
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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 herb of shortcape fleabane.
Description
Technical field: the present invention is a kind of Chinese medicine 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 can cause the damage of organs such as the heart, brain, kidney, cause as diseases such as apoplexy, heart failure, renal failures, serious threat human beings'health and life, it was reported, sickness rate in recent years has and increases trend year by year, and in, young patient constantly increases.Prevent and treat purpose in order to reach, 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: 02153750, name is called " a kind of Herba Erigerontis combination drug and medical usage thereof ", in this part application, used Fructus Schisandrae Chinensis, the problem that its exists is: Fructus Schisandrae oil can cause that respiratory system damage produces infringement to throat, bronchus, lung, shows as cough, chest pain, cyanosis, dyspnea, vocal cords edema, bronchospasm, pants, suffocates, respiratory failure etc.In light of this situation, seek that a kind of medical material compatibility is simple, therapeutic effect is desirable, does not have toxic and side effects, preparation technology's rational and effective medicine preparation is to satisfy the thing that market demand 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 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, selects for use Radix Ginseng and Herba Erigerontis as prescription of the present invention; Radix Ginseng has strongly invigorating primordial QI, 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 Herba Erigerontis blood circulation promoting and blood stasis dispelling, dredge the meridian passage; Pharmacological research shows: have vasodilator, microcirculation improvement, raising cardiac and cerebral blood-supply traffic engineering capability; The scalable blood fat suppresses platelet and erythrocyte aggregation, and blood viscosity lowering promotes fibrinolytic, improves hemorheological property; But also formation or the release that can remove oxygen-derived free radicals, inhibition histamine medium.Therefore adopt Radix Ginseng and Herba Erigerontis compatibility to make preparation, activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, improve 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 constitutes like this: calculate according to components by weight percent, the Radix Ginseng extract that it is obtained after extracting by Radix Ginseng 1～99 weight portion or corresponding weight fraction, the Herba Erigerontis extract that obtains after extracting with Herba Erigerontis 99～1 weight portions or corresponding weight fraction is made into injection, comprises: injection, powder pin, freeze-dried powder, tablet, dispersible 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 obtained after extracting by Radix Ginseng 20～80 weight portions or corresponding weight fraction, the Herba Erigerontis extract that obtains after extracting with Herba Erigerontis 80～20 weight portions or corresponding weight fraction is made.Optimizing prescriptions is, the Radix Ginseng extract that it is obtained after extracting by 30 parts of Radix Ginsengs or corresponding weight fraction, and the Herba Erigerontis extract that obtains after extracting with 70 parts of Herba Erigerontiss or corresponding weight fraction is made.Preferred formulation of the present invention is: injection, comprising: injection, powder pin, freeze-dried powder, tablet, capsule, granule, drop pill, gel, dispersible tablet, soft capsule, pellet.
Preparation method of the present invention is: 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 Herba Erigerontis, 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.Say accurately: it is an amount of to get Radix Ginseng, pulverize, and 30～95% alcohol reflux 1～5 time, each 1～5 hour, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol is re-refined, is concentrated, and crushed after being dried promptly gets Radix Ginseng extract; Get Herba Erigerontis, pulverize, 20～95% alcohol reflux 1～5 time, each 1～5 hour, collect extracting solution, reclaim ethanol, re-refine, concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, make different preparations then respectively.
The injection of preparation of the present invention prepares like this: it is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add the dissolving of injection water, regulate pH value to 6.0～6.5 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled, filter, add glucose (10mg/ml) 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 injection of preparation of the present invention prepares like this: it is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add the dissolving of injection water, regulate pH value to 6.0～6.5 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 water for injection again to certain volume, filtration, fill, sterilization, promptly.
The dispersible tablet of preparation of the present invention prepares like this: it is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, with 60%7 pure eluting, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, add 6%CMS-Na, 1.0%SDS, mixing, 95% ethanol is moistening, granulates drying, granulate adds 2.0%CMS-Na, mixing, tabletting promptly gets (CMS-Na is a carboxymethyl starch sodium, and SDS is a sodium lauryl sulphate).
The soft capsule of preparation of the present invention prepares like this: it is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, extract powder and triglyceride to be mixed into medicinal liquid at 1: 45, the softgel shell prescription is gelatin: glycerol: water=10: 3: 13, pill, promptly.
The pellet of preparation of the present invention prepares like this: it is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times; each 3 hours, collect extracting solution, reclaim ethanol; reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously; add 23.3% starch, 3.0% pregelatinized Starch, 15.0% microcrystalline Cellulose, 1.2% magnesium stearate; add in the mixer granulator, add binding agent 2%HPMC solution, granulate; drying, promptly.
The granule of preparation of the present invention prepares like this: it is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add 5% lactose, add the moistening back of ethanol and granulate, make granule, the bag film-coat, 50 ℃ of coating temperature, hydroxypropyl methylcellulose 70% dissolve with ethanol, promptly.
Tablet in the preparation of the present invention prepares like this: it is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, add 3% low-substituted hydroxypropyl cellulose, add the moistening back of ethanol and granulate, drying, tabletting, bag film-coat, wherein the preparation of coating solution is: 6% hydroxypropyl methylcellulose ethanol liquid 16.5kg, tween 80 0.38kg, Polyethylene Glycol ethanol liquid 0.48kg, Pulvis Talci 0.65kg, ethanol 30kg, promptly.
Compared with prior art, the Radix Ginseng that the present invention uses has strongly invigorating primordial QI, and multiple arteries and veins takes off invigorating the spleen to benefit the lung, the effect of promoting the production of body fluid, calming the nerves admittedly, pharmacological research shows: but Radix Ginseng human body immunity improving power, strengthen 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 Herba Erigerontis blood circulation promoting and blood stasis dispelling, dredge the meridian passage; Pharmacological research shows: have vasodilator, microcirculation improvement, raising cardiac and cerebral blood-supply traffic engineering capability; The scalable blood fat suppresses platelet and erythrocyte aggregation, and blood viscosity lowering promotes fibrinolytic, improves hemorheological property; But also formation or the release that can remove oxygen-derived free radicals, inhibition histamine medium.Therefore adopt Radix Ginseng and Herba Erigerontis compatibility to make preparation, activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, improve 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 do not select the medical material of Fructus Schisandrae Chinensis one class for use, but the little patients life-time service of its untoward reaction.Preparation of the present invention also can be used for treatment of diseases such as diabetes, hepatorenal syndrome, has effects such as antitumor and enhance immunity.
The applicant finds the particulate very easily moisture absorption of the Chinese medical concrete of this product in development process, softening, caking, and bitter taste of drug is very big simultaneously; The applicant is by after testing in a large number, granule is carried out film coating, and film-coat has certain isolating power to water vapour, light, and granule does not stick together in the process of bag film-coat, non-hygroscopic deliquescing after the film forming makes that tablet, granule, the capsule made are functional.And the applicant has been determined by experiment the suitable pH value of injection, guaranteed the stable of ginseng effective component's saponin, and the invention provides the detailed processing technology of several formulations, can be directly used in and instructs 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: extraction process screening
Modern pharmacological research proves: ginsenoside, oil lamp flavone are the labeled component and the active component of Radix Ginseng, Herba Erigerontis, are one of important onset compositions of this product, and extraction process directly influences the curative effect and the quality of product.
1. extraction of panax ginseng screening:
Decocting method: get Radix Ginseng, 8 times of water gagings soak 12h, and 100 ℃ decoct 3 times, and 3 times are respectively 2h, 2h, 1h.Merge extractive liquid, is concentrated into certain volume.Concentrated solution is divided into 3 parts, carries out assay behind the 1/3 usefulness n-butanol extraction purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.
The warm macerating method: get Radix Ginseng, 8 times of water gagings soak 12h, 60 ℃ of water-bath warm macerating 3 times, and 3 times are respectively 2h, 2h, 1h.After the extraction, decompress filter.Filtrate is divided into 3 parts, carries out assay behind the 1/3 usefulness n-butanol extraction purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.
Ethanol reflux extraction: get Radix Ginseng, the alcohol reflux with 70% 3 times, each 2h to doing, uses water dissolution with the extracting solution reclaim under reduced pressure.Aqueous solution is divided into 3 parts, carries out assay behind the 1/3 usefulness n-butanol extraction purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.
Microwave extraction method: get Radix Ginseng, put into triangular flask, extract 8 fens (moderate heats with 50% ethanol 60ml, 50ml, 40ml low fire in microwave oven respectively, middle high fire, high fire easily boiling overflows triangular flask), filter merging filtrate with suction funnel, reclaim the ethanol evaporate to dryness, use water dissolution, aqueous solution is divided into 3 parts, carry out assay behind the 1/3 usefulness n-butanol extraction purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.
Ultrasonic extraction: get Radix Ginseng, 8 times of water gagings soak 12h, put into ultrasound wave and extract, and set extraction time and be 20 fens, power 100,30 ℃ of temperature, 8 times of quantity of solvent, number of times 3 times, after the extraction, and decompress filter.Filtrate is divided into 3 parts, carries out behind the 1/3 usefulness n-butanol extraction purification
Assay carries out assay behind the 1/3 usefulness purification by macroporous resin, and 1/3 carries out the extractum quantitative determination in addition.
Saponin content %
Group extractum content % extraction Amberlyst process
Ultrasonic method 37 8.48 8.23
Microwave method 25 7.40 7.30
Circumfluence method 52 8.51 8.53
Warm macerating method 51 8.45 8.30
Decocting method 50 4.13 4.20
The screening of Herba Erigerontis extraction process:
Decocting method: get Herba Erigerontis, 8 times of water gagings soak 12h, and 100 ℃ decoct 3 times, and 3 times are respectively 2h, 2h, 1h.Merge extractive liquid, is concentrated into certain volume.Concentrated solution is divided into 3 parts, carries out assay behind the 1/3 usefulness n-butanol extraction purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.
The warm macerating method: get Herba Erigerontis, 8 times of water gagings soak 12h, 60 ℃ of water-bath warm macerating 3 times, and 3 times are respectively 2h, 2h, 1h.After the extraction, decompress filter.Filtrate is divided into 3 parts, carries out assay behind the 1/3 usefulness ethyl acetate extraction method purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.Ethanol reflux extraction: get Herba Erigerontis, the alcohol reflux with 50% 2 times, each 3h to doing, uses water dissolution with the extracting solution reclaim under reduced pressure.Aqueous solution is divided into 3 parts, carries out assay behind the 1/3 usefulness ethyl acetate extraction method purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.
Microwave extraction method: get Herba Erigerontis, put into triangular flask, extract 8 fens (moderate heats with 50% ethanol 60ml, 50ml, 40ml low fire in microwave oven respectively, middle high fire, high fire easily boiling overflows triangular flask), filter merging filtrate with suction funnel, reclaim the ethanol evaporate to dryness, use water dissolution, aqueous solution is divided into 3 parts, carry out assay behind the 1/3 usefulness ethyl acetate extraction method purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.
Ultrasonic extraction: get Herba Erigerontis, 8 times of water gagings soak 12h, put into ultrasound wave and extract, and set extraction time and be 20 fens, power 100,30 ℃ of temperature, 8 times of quantity of solvent, number of times 3 times, after the extraction, and decompress filter.Filtrate is divided into 3 parts, carries out assay behind the 1/3 usefulness ethyl acetate extraction method purification, carry out assay behind the 1/3 usefulness purification by macroporous resin, 1/3 carries out the extractum quantitative determination in addition.
General flavone content %
Group extractum content % extraction Amberlyst process
Ultrasonic 35 6.45 6.22
Microwave method 28 6.41 6.31
Circumfluence method 54 6.59 6.54
Warm macerating method 52 6.46 6.35
Decocting method 49 6.03 6.23
The screening of experimental example 2 moulding processs
The applicant finds the particulate very easily moisture absorption of the Chinese medical concrete of this product in development process, softening, caking, and bitter taste of drug is very big simultaneously; Moulding process is directly connected to the character and the absorption in vivo utilization of product, is key technology of the present invention.
(1) tablet high humidity experiment: getting three kinds of sheets, to put relative humidity be 92.5% (KNO
3Saturated solution) in the exsiccator, puts in 25 ℃ of constant incubators and observe 10d.
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.
Types of coatings time outward appearance hardness mass fraction disintegration
(t/d) (kg·m/s
2) (t/min) (％)
Film coated tablets 10 whites 42.14 ± 2.35 14 ± 1.62 99.0 ± 0.23
Coated tablet 10 off-white colors 36.26 ± 2.65 23 ± 2.21 97.8 ± 0.37
Coating 10 brownish blacks 32.21 ± 1.35 25 ± 2.20 96.8 ± 0.35 not
(2) granule: 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 weighing is placed on above-mentioned glass exsiccator interior (the weighing bottle cap is opened) in 25 ℃ of preservations, and regularly (6,12,24,48,60h) weighing is calculated as follows the moisture absorption percentage rate.
Hydroscopicity (%)=(medicated powder weight after the moisture absorption-moisture absorption prodrug grain weight amount)/moisture absorption prodrug grain weight amount * 100%
1. grouping: group coating temperature (℃) concentration of alcohol (%)
1 50 70
2 50 80
3 60 90
4 60 70
5 70 80
6 70 90
2. result: group 123456
Hydroscopicity (%) 3.50 4.44 3.81 3.88 4.14 4.12
(3) injection:
1. the selection of injection pH value: the applicant finds 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, 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 1.01 5.5 differ from 1.53
6.0 clear and bright 1.49 clear and bright 1.34
6.5 clear and bright 1.43 clear and bright 1.32
7.0 clear and bright 1.49 differ from 1.21
Differ from 1.06 7.5 differ from 1.53
Differ from 1.02 8.0 differ from 1.55
2. the selection of powder pin excipient: even for guaranteeing dried crystallization, the color and luster unanimity, fine texture has good physical strength and dissolubility faster, and the applicant has carried out the screening of excipient.
Amount of excipient (mg/ml) clarity mouldability dissolubility
The not good enough t of gelatin hydrolysate 5 differences＞20 seconds
The not good enough t of gelatin hydrolysate 10 differences＜20 seconds
Mannitol 5 difference molding t＞20 seconds
The not good enough t of mannitol 10 differences＜20 seconds
Glucose 5 clear and bright molding t＞20 seconds
Glucose 10 clear and bright molding t＜20 seconds
Test 2 results and show, adopt 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.
(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: 45, 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: 3: 13 8.5min roundings of 1 gelatin, glycerol, water, smooth, invariant color
2 gelatin, glycerol, water 15.4min hardening in 15: 0.5: 10.5, variable color
3 gelatin, glycerol 10.5min rounding, smooth, hardening slightly in 10: 3
4 gelatin, water 26.0min hardening in 10: 13, variable color
5 gelatin 35.2min hardening, variable color
The result shows that the present invention chooses the softgel shell prescription and is gelatin: glycerol: water=10: 3: 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.
The selection of surfactant: surfactant has moistening and solubilization, adds surfactant in dispersible tablet of the present invention, can promote dispersible tablet moistening in water, increases the stripping of effective ingredient.The stripping experiment of three kinds of situations of mooring husky nurse and Mo Jia surfactant in SDS, Lip river has been compared in experiment.Result's 15min accumulation stripping quantity in simulated gastric fluid (pH 1.2) is respectively 95.93%, 78.98%, 23.57%, and is wherein best with the result of extraction of SDS.In addition, analyze from tablet forming technique, because that husky nurse viscosity is moored in the Lip river is bigger, sticking when causing tabletting easily is the adjuvant of prescription so select SDS for use.
1. prescription CMS-Na (in add) % CMS-Na (adding) % SDS% disintegration time (min)
1 4 1.0 0.5 2.63
2 4 2.0 1.5 1.71
3 5 1.0 1.0 1.52
4 5 2.0 0.5 1.05
5 6 1.0 1.5 0.91
6 6 2.0 1.0 0.73
The result shows, optimizing prescriptions is 6%CMS-Na (in add), 2.0%CMS-Na (adding), 1.0%SDS.
CMS-Na is a carboxymethyl starch sodium, and SDS is a sodium lauryl sulphate.
2. determination of dissolution rate (1) condition determination is used changes the dissolution that the basket method is measured dispersible tablet, and compares with ordinary tablet.Dissolution medium: simulated gastric fluid (pH1.2) 900ml; Rotating speed: 100r/min; (2) assay method (1,5,10,15,20,30,45min) sampling 5ml at the fixed time, 0.8 μ m microporous filter membrane filters; Determined by ultraviolet spectrophotometry trap, standard curve method are calculated content and accumulative total stripping percentage rate.
Dissolution
Sample 15 10 15 20 30 45 (min)
Ordinary tablet 5.1 15.4 25.7 41.3 48.5 58.2 64.5
Dispersible tablet 15.7 56.8 84.6 97.2 100.0 100.0 100.0
The result shows that the dissolution rate of dispersible tablet is far faster than ordinary tablet.
(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 20.0 - 7.2 15.0 1.0
2 - 7.0 11.7 5.0 0.5
3 23.3 3.0 15.0 - 1.2
4 30.0 10.0 - 6.1 0.9
5 36.7 12.0 8.3 12.8 1.2
6 40.0 8.0 12.8 7.2 -
Prescription Y1 Y2 Y3 Y4 Y5 ∑ y
1 2.0 1.5 6.0 7.0 4.0 20.5
2 2.5 2.0 6.5 4.5 5.5 21.0
3 8.0 4.0 10.0 10.0 10.0 42.0
4 6.0 2.5 7.0 4.0 3.0 22.5
5 7.0 3.5 9.0 6.5 7.0 33.0
6 1.0 0.5 15 2.0 1.0 6.0
The result shows that No. 3 is best prescription: starch 23.3%, pregelatinized Starch 3.0%, microcrystalline Cellulose 15.0%, magnesium stearate 1.2%.
Experimental example 3: to the influence of stasis syndrome rat blood rheological characteristic
Test 1 group: the capsule that Radix Ginseng, Fructus Schisandrae Chinensis, Herba Erigerontis, Radix Ophiopogonis make;
Test 2 groups: capsule 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 5.96 ± 0.58 8.12 ± 1.04 14.85 ± 1.75 1.76 ± 0.18 0.46 ± 0.24 7.86 ± 1.21 8.31 ± 1.23 0.77 ± 0.17
Test 2 group 6.0 5.63 ± 1.01 7.83 ± 0.50 14.73 ± 1.70 1.72 ± 0.21 0.43 ± 0.05 7.68 ± 3.22 8.22 ± 2.08 0.76 ± 0.28
The result shows, preparation good effect of the present invention, and do not select Fructus Schisandrae Chinensis for use, do not have its untoward reaction that brings and anaphylaxis.
Experimental example 4: platelet aggregation mensuration
Healthy rabbits, male and female are usefulness all, body weight 2～3kg, clear-headed certainly rabbit carotid artery is got blood, is collected in the centrifuge tube of silication with 3.8% sodium citrate anticoagulant, and blood and anticoagulant volume ratio are 9: 1.Respectively through 1000 and the centrifugal 10min of 3000rpm get platelet rich plasma (PRP) and platelet poor plasma (PPP).Press the BornShi turbidimetry, with BS-631 type autobalance platelet aggregation instrument, PRP is hatched 15min with the medicinal liquid of variable concentrations earlier, adds derivants such as ADP, AA or PAF again, and the waveform of record platelet aggregation also calculates maximum agglutination rate.Platelet aggregation inhibition rate is calculated as follows: assemble suppression ratio (%)=(1-delivery tube aggregation rate/control tube aggregation rate) * 100
The dense ADP AA of medicine PAF
Medicineρ (％) ρ(3μmol/L) ρ(0.35mmol/L) ρ(7.2nmol/L)
Contrast 59.5 ± 2.4 67.3 ± 2.5 57.6 ± 3.1
Radix Ginseng extractive solution 2.0 38.1 ± 3.1 27.4 ± 2.7 48.3 ± 2.5
Herba Erigerontis extract liquid 2.0 33.1 ± 4.1 25.1 ± 2.5 45.5 ± 2.3
Extracting solution 2.0 29.1 of the present invention ± 3.3 21.4 ± 3.1 38.5 ± 2.7
Aspirin 54mg/L 56.3 ± 2.2 5.2 ± 1.3 55.2 ± 2.4
Above result shows that prescription curative effect of the present invention is better than independent medication, prove that the combination of Radix Ginseng, oil lamp can play the effect of Synergistic, and its effect is also apparent in view.
Experimental example 5: preparation of the present invention is to the research of Cor Leporis myocardial ischemia one reperfusion injury
30 of New Zealand's white rabbit, male and female are regardless of, body weight (1.8 ± 0.5) kg.At coronary artery ligation ischemia 40min, pour into 40min again, be divided into treatment group (I group) at random: 10min behind the ligation coronary artery begins through ear vein with electronics trace constant flow pump constant speed (0 4mL/min) infusion injection 2mL/kg of the present invention.Verapamil group (II group): infusion verapamil medicinal liquid 0.25mg/kg; Ischemia-reperfusion group (matched group): infusion 5% Glucose Liquid 30mL.In the experiment, except that administration time, all with fast infusion 5% glucose injection to replenish the forfeiture of body fluid.Liquid is to replenish the forfeiture of body fluid.Index: in the experimentation, lead physiology record instrument (RM-6000 type, Japanese photoelectricity company) with four and measure LVSP.
Ischemia 10min ischemia 40min pours into 40min again before the group n ischemia
I organizes 10 13.17 ± 1.12 9.06 ± 2.23 9.80 ± 1.60 12.10 ± 3.20
II organizes 10 14.53 ± 1.39 9.02 ± 1.58 9.98 ± 1.47 10.81 ± 1.72
Matched group 10 13.40 ± 1.21 9.42 ± 1.46 8.82 ± 0.83 7.23 ± 1.11
The result shows, matched group is at ischemia and when pouring into again, and LVSP is the decline of carrying out property, ischemia 40min, and all a little higher than matched group of each treatment group LVSP pours into 40min again, and each treatment group LVSP gos up to be higher than matched group I group and is better than the II group.Preparation of the present invention has good therapeutical effect to improving myocardial ischemia and reperfusion injury.
Experimental example 6: 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 2003 ± 186
Glutamic oxaloacetic transaminase, GOT (u/l) 231 ± 45 2990 ± 85 2073 ± 143
Lactic dehydrogenase isoenzyme (u/l) 248 ± 38 5904 ± 731 3909 ± 612
Malonaldehyde (nmol/mg) 0.88 ± 0.08 1048 ± 0.12 1.16 ± 0.12
Superoxide dismutase (u/mg) 26.15 ± 0.97 10.94 ± 0.88 16.02 ± 0.21
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: Radix Ginseng 990g, Herba Erigerontis 10g
Get Radix Ginseng, pulverize, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, add 3% low-substituted hydroxypropyl cellulose, adding the moistening back of ethanol granulates, drying, tabletting, bag film-coat, wherein the preparation of coating solution is: 6% hydroxypropyl methylcellulose ethanol liquid 16.5kg, tween 80 0.38kg, Polyethylene Glycol ethanol liquid 0.48kg, Pulvis Talci 0.65kg, ethanol 30kg, promptly get tablet, each 2, every day 3 times.
Embodiments of the invention 2: Radix Ginseng 10g, Herba Erigerontis 990g
Get Radix Ginseng, pulverize, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add 5% lactose, add the moistening back of ethanol and granulate, make granule, the bag film-coat, 50 ℃ of coating temperature, hydroxypropyl methylcellulose 70% dissolve with ethanol promptly gets granule.
Embodiments of the invention 3: take by weighing Radix Ginseng 300g, Herba Erigerontis 700
Get Radix Ginseng, pulverize, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add the dissolving of injection water, regulate pH value to 6.0～6.5 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 water for injection again to certain volume, filtration, fill, sterilization promptly get injection.
Embodiments of the invention 4: take by weighing Radix Ginseng 800g, Herba Erigerontis 200g,
Get Radix Ginseng, pulverize, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add the dissolving of injection water, regulate pH value to 6.0～6.5 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled, filter, add glucose (10mg/ml) 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 injectable powder.
Embodiments of the invention 5: Radix Ginseng 200g, Herba Erigerontis 800g
Get Radix Ginseng, pulverize, 30% alcohol reflux 1 hour, the collection extracting solution filters, concentrating under reduced pressure, decompression recycling ethanol, the reuse n-butanol extraction is collected extract, the reclaim under reduced pressure n-butyl alcohol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 20% alcohol reflux 1 hour, collect extracting solution, reclaim ethanol, the reuse macroporous adsorbent resin is refining, 50% ethanol elution is collected eluent, reclaims ethanol, after the drying again with the Radix Ginseng extract mix homogeneously, add 5% lactose, add the moistening back of ethanol and granulate, make granule, bag film-coat, (25 ℃ of coating temperature, hydroxypropyl methylcellulose 75% dissolve with ethanol), encapsulated, promptly get capsule.
Embodiments of the invention 6: take by weighing Radix Ginseng 300g, Herba Erigerontis 700g
Get Radix Ginseng, pulverize, 95% alcohol reflux 5 times, each 5 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse n-butanol extraction is collected extract, and the reclaim under reduced pressure n-butyl alcohol concentrates, and crushed after being dried promptly gets Radix Ginseng extract; Get Herba Erigerontis, pulverize 95% alcohol reflux 5 times, each 5 hours, collect extracting solution, reclaim ethanol, the reuse macroporous adsorbent resin is refining, 50% ethanol elution, collect eluent, reclaim ethanol, after the drying again with the Radix Ginseng extract mix homogeneously, splash into methyl-silicone oil: the freezing mixture of liquid paraffin (3: 1) promptly gets drop pill.
Embodiments of the invention 7: take by weighing Radix Ginseng 400g, Herba Erigerontis 600g
It is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, extract powder and triglyceride to be mixed into medicinal liquid at 1: 45, the softgel shell prescription is gelatin: glycerol: water=10: 3: 13, pill promptly gets soft capsule.
Embodiments of the invention 8: take by weighing Radix Ginseng 600g, Herba Erigerontis 400g
It is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, add 6%CMS-Na, 1.0%SDS, mixing, 95% ethanol is moistening, granulates, drying, granulate adds 2.0%CMS-Na, mixing, tabletting promptly gets dispersible tablet.
Embodiments of the invention 9: take by weighing Radix Ginseng 500g, Herba Erigerontis 500g
It is an amount of to get Radix Ginseng, pulverizes 70% alcohol reflux 3 times, each 2 hours, collect extracting solution, filter, concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, uses 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times; each 3 hours, collect extracting solution, reclaim ethanol; reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously; add 23.3% starch, 3.0% pregelatinized Starch, 15.0% microcrystalline Cellulose, 1.2% magnesium stearate; add in the mixer granulator, add binding agent 2%HPMC solution, granulate; drying promptly gets pellet.
Claims (13)
1, a kind of Chinese medicine 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 Radix Ginseng 1～99 weight portion or corresponding weight fraction, the Herba Erigerontis extract that obtains after extracting with Herba Erigerontis 99～1 weight portions or corresponding weight fraction is made into injection, comprise: injection, the powder pin, freeze-dried powder, tablet, dispersible 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 preparation of the described this 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 Radix Ginseng 20～80 weight portions or corresponding weight fraction, the Herba Erigerontis extract that obtains after extracting with Herba Erigerontis 80～20 weight portions or corresponding weight fraction is made.
3, according to the Chinese medicine preparation of the described this treatment cardiovascular and cerebrovascular disease of claim 2, it is characterized in that: calculate according to components by weight percent, the Radix Ginseng extract that it is obtained after extracting by 30 parts of Radix Ginsengs or corresponding weight fraction, the Herba Erigerontis extract that obtains after extracting with 70 parts of Herba Erigerontiss or corresponding weight fraction is made.
4, according to the Chinese medicine preparation of claim 1,2 or 3 described this treatment cardiovascular and cerebrovascular diseases, it is characterized in that: preferred preparation is: injection, comprising: injection, powder pin, freeze-dried powder, tablet, capsule, granule, drop pill, gel, dispersible tablet, soft capsule, pellet.
5, as the preparation method of the Chinese medicine 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 Herba Erigerontis, 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.
6, according to the preparation method of the Chinese medicine preparation of the described treatment cardiovascular and cerebrovascular disease of claim 5, it is characterized in that: it is an amount of to get Radix Ginseng, pulverizes 30～95% alcohol reflux 1～5 time, each 1～5 hour, collect extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, re-refine, concentrate, crushed after being dried promptly gets Radix Ginseng extract; Get Herba Erigerontis, pulverize, 20～95% alcohol reflux 1～5 time, each 1～5 hour, collect extracting solution, reclaim ethanol, re-refine, concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, make different preparations then respectively.
7, according to the preparation method of the Chinese medicine preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the injection of described preparation prepares like this: it is an amount of to get Radix Ginseng, pulverizes, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, use 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add the dissolving of injection water, regulate pH value to 6.0～6.5 with 10% sodium hydroxide solution, add injection water and 0.1% needle-use activated carbon, the mixed solution heated and boiled, filter, add glucose 10mg/ml 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.
8, according to the preparation method of the Chinese medicine preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the injection of described preparation prepares like this: it is an amount of to get Radix Ginseng, pulverizes, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, use 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add the dissolving of injection water, regulate pH value to 6.0～6.5 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 water for injection again to certain volume, filtration, fill, sterilization, promptly.
9, according to the preparation method of the Chinese medicine 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: it is an amount of to get Radix Ginseng, pulverizes, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, use 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, add 6% carboxymethyl starch sodium, 1.0% sodium lauryl sulphate, mixing, 95% ethanol is moistening, granulates, drying, granulate adds 2.0% carboxymethyl starch sodium, mixing, tabletting, promptly.
10, according to the preparation method of the Chinese medicine 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: it is an amount of to get Radix Ginseng, pulverizes, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, use 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, extract powder and triglyceride to be mixed into medicinal liquid at 1: 45, the softgel shell prescription is gelatin: glycerol: water=10: 3: 13, pill, promptly.
11, according to the preparation method of the Chinese medicine 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: it is an amount of to get Radix Ginseng, pulverizes, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, use 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times; each 3 hours, collect extracting solution, reclaim ethanol; reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously; add 23.3% starch, 3.0% pregelatinized Starch, 15.0% microcrystalline Cellulose, 1.2% magnesium stearate; add in the mixer granulator, add binding agent 2%HPMC solution, granulate; drying, promptly.
12, according to the preparation method of the Chinese medicine preparation of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the granule of described preparation prepares like this: it is an amount of to get Radix Ginseng, pulverizes, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, use 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, reuse ethyl acetate extraction, extract concentrate, after the drying again with the Radix Ginseng extract mix homogeneously, add 5% lactose, add the moistening back of ethanol and granulate, make granule, the bag film-coat, 50 ℃ of coating temperature, hydroxypropyl methylcellulose 70% dissolve with ethanol, promptly.
13, according to the preparation method of the Chinese medicine 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: it is an amount of to get Radix Ginseng, pulverizes, 70% alcohol reflux 3 times each 2 hours, is collected extracting solution, filter concentrating under reduced pressure, decompression recycling ethanol, the reuse macroporous adsorbent resin is refining, use 60% ethanol elution, collect effluent to colourless, decompression recycling ethanol, concentrated, dry, pulverizing promptly get Radix Ginseng extract; Get Herba Erigerontis, pulverize 50% alcohol reflux 2 times, each 3 hours, collect extracting solution, reclaim ethanol, the reuse ethyl acetate extraction, extract concentrates, after the drying again with the Radix Ginseng extract mix homogeneously, add 3% low-substituted hydroxypropyl cellulose, add the moistening back of ethanol and granulate, drying, tabletting, bag film-coat, wherein the preparation of coating solution is: 6% hydroxypropyl methylcellulose ethanol liquid 16.5kg, tween 80 0.38kg, Polyethylene Glycol ethanol liquid 0.48kg, Pulvis Talci 0.65kg, ethanol 30kg, promptly.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103006722A (en) * | 2013-01-05 | 2013-04-03 | 宁辉 | Xiaoaiping composition, dropping pill and preparation method thereof |
| CN105942519A (en) * | 2016-04-27 | 2016-09-21 | 周飞燕 | Health-care food capable of reducing blood lipid and added with ginseng extract |
-
2004
- 2004-05-10 CN CN 200410022511 patent/CN1569159A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103006722A (en) * | 2013-01-05 | 2013-04-03 | 宁辉 | Xiaoaiping composition, dropping pill and preparation method thereof |
| CN105942519A (en) * | 2016-04-27 | 2016-09-21 | 周飞燕 | Health-care food capable of reducing blood lipid and added with ginseng extract |
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