CN1634255A - Compound formulation of breviscapine for treating cardiovascular and cerebrovascular diseases and its preparing process - Google Patents
Compound formulation of breviscapine for treating cardiovascular and cerebrovascular diseases and its preparing process Download PDFInfo
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Abstract
The invention provides a compound formulation of breviscapine for treating cardiovascular and cerebrovascular diseases and its preparing process by using herb of shortcape fleabane and pseudo-ginseng as the raw material. A macroscopic resin edulcoration procedure is employed in the preparation process.
Description
Technical field: the present invention is a kind of compound formulation of breviscapine 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 angina pectoris are commonly encountered diseases, the frequently-occurring diseases of middle-aged and elderly people.Mean that coronary atherosclerosis causes coronary insufficiency, the retrosternal pain that the rapid temporary transient hypoxic-ischemic of cardiac muscle causes.The category such as " thoracic obstruction ", " cardiopalmus ", " angina pectoris " that belongs to the traditional Chinese medical science.Primary disease Chang Fanfu outbreak, touching difficulty heals, and the healthy of people in serious harm.Prevent and treat purpose in order to reach, a large amount of research has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; As: number of patent application is: 95101731, name is called the patent application technology of " compound formulation of notoginseng ", and it is used for the treatment of the disease for the treatment of cardiac and cerebral vascular diseases; But its drug ratio scope is too wide in range, many vital Basic Experiment Study all lack: do not have best medicine to, do not have best proportion compatibility threshold, do not have extract preparation technology, do not have detailed preparation process, can't instruct production application at all.Pharmaceutical preparation for the treatment disease, must be to compatibility of drugs in line with very rigorous and attitude science, through rational, creative, best composition of prescription, the proportion compatibility of a large amount of pharmacological effect experiment screenings, otherwise the curative effect of product and application can not get any assurance, have in addition can cause inconceivable consequence.And, whether one best of breed, best proportioning are arranged between Radix Notoginseng, Herba Erigerontis, the Semen Ginkgo in the prescription that this patent application provides, ambigendi locus, further inquire into the right pharmacological mechanism of this medicine, preferred optimal proportion, so amplify the compatibility research of prescription, the technical study of product formulation is very necessary.Particularly for injection, its security requirement is higher than oral formulations, and the process for refining of extract is directly connected to the clarity of finished product, stability, has only high-quality raw materials just can obtain stay-in-grade finished product.
Summary of the invention: the objective of the invention is to: a kind of compound formulation of breviscapine for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof is provided; The present invention is directed to prior art, according to cardiovascular and cerebrovascular disease such as coronary heart disease, cerebral thrombosis, alzheimer disease etc. all contract because of blood vessel is narrow, reason such as blood flow minimizing causes the diseases induced principle of blood supply insufficiency, on the basis of experiment screening, adopt Herba Erigerontis and Radix Notoginseng compatibility to make preparation, optimize best prescription and technology; The product that obtains, particularly ejection preparation product can play 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, alzheimer disease 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 percentage by weight, it is made by Herba Erigerontis 15%～20% and Radix Notoginseng 80%～85%, or corresponding weight fraction Herba Erigerontis extract that obtains after extracting and the Radix Notoginseng extract that corresponding weight fraction obtains after extraction are made.Say accurately: calculate according to percentage by weight, it is made by Herba Erigerontis 18% and Radix Notoginseng 82%, or corresponding weight fraction Herba Erigerontis extract that obtains after extracting and the Radix Notoginseng extract that corresponding weight fraction obtains after extraction are made.Preparation of the present invention is: injection comprises: all acceptable dosage forms on the pharmaceuticss such as injection, powder pin, freeze-dried powder, infusion solutions, dispersible tablet, tablet, capsule, soft capsule, microcapsule, granule, micropill, pill, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, soft extract, extractum and membrane.Say accurately: preferred preparation of the present invention is: injection comprises: injection, powder pin, freeze-dried powder or infusion solutions.
The preparation method of the compound formulation of breviscapine of treatment cardiovascular and cerebrovascular disease of the present invention is: get Herba Erigerontis, 20%～80% alcohol reflux 1～5 time, each 20～60 minutes, filter, merging filtrate reclaims ethanol, refining with D101 type macroporous adsorbent resin, collect 10～60% ethanol elution, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 40～90% alcohol reflux of 8～12 times of amounts 1～5 time, each 1～3 hour, refining with D101 type macroporous adsorbent resin, collect 30%～80% ethanol elution, after the drying again with the Herba Erigerontis extract mix homogeneously, make different preparations then respectively.Say accurately: get Herba Erigerontis, add 60% alcohol reflux 2 times of 15 times of amounts, each 30 minutes, filter, merging filtrate reclaims ethanol, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 3 times of column volumes, and water consumption is 3 times of column volumes, and ethanol elution concentration is 40%, ethanol consumption eluting is 3 times of column volumes, collect eluent, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 80% alcohol reflux of 10 times of amounts 3 times, each 1.5 hours, refining with D101 type macroporous adsorbent resin, adsorption rate was the medicinal liquid that per hour passes through 2 times of column volumes, water consumption is 3 times of column volumes, ethanol elution concentration is 60%, and ethanol consumption eluting is 3 times of column volumes, collects eluent, after the drying again with the Herba Erigerontis extract mix homogeneously, make different preparations then respectively.
Get Herba Erigerontis extract, Radix Notoginseng extract, add water for injection, and add 10% sodium chloride, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boils 30 minutes, puts cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5～8.5, benefit adds to the full amount of water for injection, filtering with microporous membrane through 0.25～0.45 μ m, fill was sterilized 30 minutes, and was promptly got great transfusion preparation for 115 ℃.
Get Herba Erigerontis extract, Radix Notoginseng extract, add water for injection, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 7.5～8.5, in medicinal liquid: it is caffolding agent that the ratio of caffolding agent=1: 3 adds dextran, and mixing is through the filtering with microporous membrane of 0.25～0.45 μ m, fill, lyophilization, lyophilisation condition :-10 ℃ of pre-freezes 3 hours ,-40 ℃ of pre-freezes began evacuation after 4 hours, and be warming up to-35 ℃, kept 2 hours; Be warming up to-30 ℃, kept 5 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to--10 ℃, kept 10 hours; Be warming up to 0 ℃, kept 2 hours; Be warming up to 10 ℃, kept 2 hours; Be warming up to 20 ℃, kept 2 hours; Be warming up to 30 ℃, kept 2 hours, promptly get lyophilized injectable powder.
Get Herba Erigerontis extract, Radix Notoginseng extract, add water for injection, stir evenly, cold preservation filters, and filtrate adds 0.1% active carbon, boiled 30 minutes, put cold, be filtered to clear and bright, with 10%NaOH adjust pH 7.5～8.5, filtering with microporous membrane through 0.25～0.45 μ m, spray drying, packing promptly gets injectable powder.
Get Herba Erigerontis extract, Radix Notoginseng extract, add water for injection, add 0.1% active carbon, boiled 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5～8.5, benefit adds to the full amount of water for injection, filtering with microporous membrane through 0.25～0.45 μ m, fill was sterilized 30 minutes, and was promptly got injection for 115 ℃.
Compared with prior art, the applicant advanced lot of experiments, and filtering out effective proportion compatibility threshold for the treatment of diseases such as angina pectoris is Herba Erigerontis 15%～20% and Radix Notoginseng 80%～85%, and best proportion compatibility is Herba Erigerontis 18% and Radix Notoginseng 82%.The result has great difference and different with the application of " compound formulation of notoginseng ".And, good, the steady quality of prepared product appearance of employing macroporous resin remove impurity.
For proving that medicine provided by the invention has effective effect, the applicant has carried out a series of experiments;
Experimental example 1: prescription research
[1] different formulations pharmacodynamics comparative study
The influence of dog acute myocardial ischemia: select 35 of healthy adult dogs to be divided into 7 groups, 5 every group, adopt arteria coronaria left anterior descending branch ligation method to cause the acute myocardial ischemia model, sham operated rats (is opened behind the breast only threading, is not done ligation; Normal saline 2ml/kg); Model group (not only threading but also ligation; Normal saline 22ml/kg); Oil lamp/Radix Notoginseng group: be called for short lamp seven (20/80; The model administration; 1.31g/kg); Semen Ginkgo/Radix Notoginseng group: be called for short silver seven (20/80; The model administration; 1.31g/kg); Oil lamp/Radix Notoginseng/Semen Ginkgo group: be called for short lamp Radix Notoginseng (10/10/80; The model administration; 1.31g/kg); Positive control sorbitrate group: be called for short sorbitrate (model administration; 0.34mg/kg).After administration 30,60,90,120,180min writes down 30 mapping point visceral pericardium electrocardiograms.
Model group 275.31 ± 16.05 279.40 ± 16.5 280.1 ± 15.46 283.7 ± 21.31 285.5 ± 22.34 282.37 ± 11.63
Lamp seven silver medals 279.12 ± 23.81 249.32 ± 6.11 242.88 ± 14.92 226.2 ± 4.93 197.66 ± 8.35 161.34 ± 33.10
Silver 7 268.80 ± 31.05 268.19 ± 11.35 266.29 ± 21.4 255.88 ± 27.2 248.17 ± 9.30 209.67 ± 15.64
Lamp 7 277.17 ± 24.62 279.22 ± 3.17 262.86 ± 15.99 256.6 ± 2.97 227.68 ± 7.15 211.31 ± 31.17
Sorbitrate 298.01 ± 11.95 278.45 ± 18.3 253.96 ± 12.73 234.14 ± 31.89 186.10 ± 13.04 146.69 ± 21.65
By experimental result as can be known, the significant effectively compatibility of the influence of dog acute myocardial ischemia is Herba Erigerontis and Radix Notoginseng.
[2] to the comparative study of different proportioning pharmacodynamics
The influence of dog acute myocardial ischemia: select 65 of healthy adult dogs to be divided into 13 groups, 5 every group, adopt arteria coronaria left anterior descending branch ligation method to cause the acute myocardial ischemia model, sham operated rats (is opened behind the breast only threading, is not done ligation; Normal saline 2ml/kg); Model group (not only threading but also ligation; Normal saline 22ml/kg); 10/90 group of oil lamp/Radix Notoginseng: be called for short 10/90 group of (model administration; 1.31g/kg); 15/85 group of oil lamp/Radix Notoginseng: be called for short 15/85 (model administration; 1.31g/kg); 18/82 group of oil lamp/Radix Notoginseng: be called for short 18/82 (model administration; 1.31g/kg); 20/80 group of oil lamp/Radix Notoginseng: be called for short 20/80 (model administration; 1.31g/kg); 30/70 group of oil lamp/Radix Notoginseng: be called for short 30/70 (model administration; 1.31g/kg); 30/70 group of oil lamp/Radix Notoginseng: be called for short 40/60 (model administration; 1.31g/kg); 50/50 group of oil lamp/Radix Notoginseng: be called for short 50/50 (model administration; 1.31g/kg); 60/40 group of oil lamp/Radix Notoginseng: be called for short 60/40 (model administration; 1.31g/kg); 80/20 group of oil lamp/Radix Notoginseng: be called for short 80/20 (model administration; 1.31g/kg); 90/10 group of oil lamp/Radix Notoginseng: be called for short 90/10 (model administration; 1.31g/kg); Positive control sorbitrate group: be called for short sorbitrate (model administration; 0.34mg/kg).After administration 30,60,90,120,180min writes down 30 mapping point visceral pericardium electrocardiograms.
Behind the medicine
Value (100%) 30min 60min 90min 120min 180min before the group medicine
Model group 275.31 ± 16.05 279.40 ± 16.5 280.1 ± 15.46 283.7 ± 21.31 285.5 ± 22.34 282.37 ± 11.63
10/90???256.76±21.42???261.23±17.43???258.0±24.82???254.7±26.04????252.35±31.17???252.2±28.97
15/85???268.82±30.04???257.15±14.89???246.76±22.1???225.81±21.1????198.49±7.36????169.63±25.65
18/82???269.30±20.53???241.32±7.20????240.83±11.14??224.1±6.54?????196.69±4.29????166.25±21.67
20/80???279.12±23.81???249.32±6.11????242.88±14.92??226.2±4.93?????197.66±8.35????16134±33.10
30/70???261.76±21.42???260.13±13.42???252.0±22.44???244.7±21.02????232.17±11.14???202.2±21.91
40/60???258.19±11.57???262.83±17.29???256.0±15.62???254.3±27.08????250.32±33.83???212.5±18.7
50/50???276.72±17.47???279.24±16.48???278.0±34.80???264.8±16.27????252.09±21.19???232.2±13.14
60/40???282.35±21.29???288.20±8.41????279.1±21.87???264.3±20.01????241.39±11.18???210.3±28.01
80/20???276.26±24.49???278.13±16.40???268.0±25.11???250.1±16.03????242.35±39.11???233.2±26.81
90/10???272.21±18.43???272.56±17.12???272.75±18.01??272.09±17.86???271.2±17.46????267.32±18.55
Sorbitrate 298.01 ± 11.95 278.45 ± 18.3 253.96 ± 12.73 234.14 ± 31.89 186.10 ± 13.04 146.69 ± 21.65
By experimental result as can be known, effectively the proportion compatibility threshold is Herba Erigerontis 15%～20% and Radix Notoginseng 80%～85%, and best proportion compatibility is Herba Erigerontis 18% and Radix Notoginseng 82%
Experimental example 2: process for refining research
(1) Radix Notoginseng
1. adsorption rate is to the influence (BV/h, the medicinal liquid multiple with respect to the resin column volume that per hour passes through) of absorption
Last sample speed (BV/h) adsorbance (mg/ml)
2????????????????????7.08
4????????????????????6.12
6????????????????????5.07
2. the water elution consumption determines
Water consumption (with respect to column volume) total saponins loss rate % eluent character
1 times of 2.88 muddiness
2 times of 1.05 muddiness
3 times of 0.58 clarification
4 times of 0.41 clarification
5 times of 0.30 clarification
3. ethanol elution concentration determines
Total saponin content % in the concentration of alcohol % total saponins retention rate % solid content yield % solid content
50?????????????77.05???????????7.54????????????82.65
60?????????????89.20???????????8.98????????????95.20
70?????????????90.11???????????11.63???????????60.14
4. the ethanol elution consumption determines
1 times 2 times 3 times of ethanol consumptions (with respect to column volume)
Total saponins eluting rate % 88.54 91.01 94.12
(2) Herba Erigerontis
1. adsorption rate is to the influence (BV/h, the medicinal liquid multiple with respect to the resin column volume that per hour passes through) of absorption
Last sample speed (BV/h) adsorbance (mg/ml)
3?????????????????????????????7.01
5?????????????????????????????6.10
7?????????????????????????????5.32
2. the water elution consumption determines
Water consumption (with respect to column volume) total flavones loss rate % eluent character
1 times of 2.91 muddiness
2 times of 1.23 muddiness
3 times of 0.55 clarification
4 times of 0.40 clarification
5 times of 0.31 clarification
3. ethanol elution concentration determines
General flavone content % in the concentration of alcohol % total saponins retention rate % solid content yield % solid content
30????????????77.24?????????????7.53????????????80.48
40??????????89.11????????8.90?????????95.31
50??????????90.32????????10.21????????62.15
4. the ethanol elution consumption determines
1 times 2 times 3 times of ethanol consumptions (with respect to column volume)
Total flavones eluting rate % 87.31 90.85 94.23
Determine that by experimental result the Radix Notoginseng extract process for refining: adsorption rate is 2BV/h, water consumption is 3 times of column volumes, and ethanol elution concentration is 60%, and ethanol consumption eluting is 3 times of column volumes; Oil lamp extract process for refining: adsorption rate is 3BV/h, and water consumption is 3 times of column volumes, and ethanol elution concentration is 40%, and ethanol consumption eluting is 3 times of column volumes.
(3) refining front and back purity and injection stability test are relatively
Stability test
Group Radix Notoginseng total arasaponins oil lamp total flavones 3 months 6 months 12 months 18 months
Purity (%) purity (%)
Refining preceding 47.4 48.6-+++
Refining back 89.0 75.8----
Annotate: (-) is negative, (+) positive (having precipitation to separate out).
By experimental result as can be known, macroreticular resin absorbing method is to the refining purification of thick Radix Notoginseng total arasaponins, and eccysis impurity also limits water-insoluble component content, makes its purity up to more than 88%, and dissolving is good and stable, has guaranteed the steady quality of its parenteral solution of preparation.
Experimental example 3: preparation pharmacodynamic experiment
The rat coronary artery ligation causes the influence of myocardial infarction: male Wistar rat 40 is divided into 4 groups at random with animal, be Sham-operated control group, model control group, oral liquid 0.3g/kg of the present invention group, injection 0.3g/kg of the present invention group, every group 8, each group is gastric infusion respectively, and every day 1 time for three days on end.1h after the last administration is with pentobarbital anesthesia, tracheal intubation, artificial respiration.Open breast in the 3rd～4 intercostal,, cause occlusive arteria coronaria district myocardial infarction apart from coronary artery outlet 5mm place's ligation left anterior descending coronary artery.Behind 4h, use the electromagnetic flowmeter determination coronary artery blood flow, and measure the infarcted region area percentage.The results are shown in Table 3, the coronary flow of medication group significantly increases, and the infarcted region area obviously reduces (comparing P with model control group all＜0.01).
The influence of coronary artery blood flow and infarct size after the table 3 pair rat coronary artery ligation
| Group | Coronary flow (ml/min.100g) | Cerebral infarction dead band area percentage (%) |
| Sham operated rats | ????55.02±1.16 | ????- |
| Model group | ????32.35±2.73 | ????8.06±1.20 |
| Injection group 0.3g/kg of the present invention | ????42.66±3.53 | ????5.61±0.94 |
| Oral liquid group 0.3g/kg of the present invention | ????37.70±2.25 | ????6.12±0.47 |
By experimental result as can be known, pharmaceutical preparation of the present invention causes that to coronary occlusion the myocardial ischemia situation can significantly increase coronary flow, and obviously reduces myocardial infarction district area.
Concrete embodiment:
Embodiments of the invention 1: Herba Erigerontis 200g, Radix Notoginseng 800g
Get Herba Erigerontis, add 20% alcohol reflux 20 minutes of 10 times of amounts, filter, merging filtrate reclaims ethanol, and is refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 2 times of column volumes, water consumption is 1 times of column volume, and ethanol elution concentration is 10%, and ethanol consumption eluting is 1 times of column volume, collect eluent,, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 40% alcohol reflux of 8 times of amounts 1 hour, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 3 times of column volumes, and water consumption is 1 times of column volume, and ethanol elution concentration is 30%, ethanol consumption eluting is 1 times of column volume, collects eluent, after the drying again with the Herba Erigerontis extract mix homogeneously, add 2% methylcellulose, add the moistening back of water and granulate, mixing, incapsulate, promptly get capsule, this product oral, three times on the one, each 2.
Embodiments of the invention 2: Herba Erigerontis 150g, Radix Notoginseng 850g
Get Herba Erigerontis, add 80% alcohol reflux 5 times of 18 times of amounts, each 60 minutes, filter, merging filtrate reclaims ethanol, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 6 times of column volumes, and water consumption is 5 times of column volumes, ethanol elution concentration is 60%, ethanol consumption eluting is 3 times of column volumes, collects eluent, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 90% alcohol reflux of 12 times of amounts 5 times, each 3 hours, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 7 times of column volumes, and water consumption is 5 times of column volumes, and ethanol elution concentration is 80%, ethanol consumption eluting is 3 times of column volumes, collects eluent, after the drying again with the Herba Erigerontis extract mix homogeneously, add methylcellulose 2%, it is moistening to add water, make granule, drying adds 0.3% magnesium stearate, tabletting, the bag film-coat promptly gets tablet.
Embodiments of the invention 3: Herba Erigerontis 180g, Radix Notoginseng 820g
Get Herba Erigerontis, add 60% alcohol reflux 2 times of 15 times of amounts, each 30 minutes, filter, merging filtrate reclaims ethanol, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 3 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 40%, ethanol consumption eluting is 3 times of column volumes, collects eluent, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 80% alcohol reflux of 10 times of amounts 3 times, each 1.5 hours, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 2 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 60%, and ethanol consumption eluting is 3 times of column volumes, collects eluent,, after the drying again with the Herba Erigerontis extract mix homogeneously, add low-substituted hydroxypropyl cellulose 3%, it is moistening to add water, make granule, drying promptly gets granule.
Embodiments of the invention 4: Herba Erigerontis 170g, Radix Notoginseng 830g
Get Herba Erigerontis, add 60% alcohol reflux 2 times of 15 times of amounts, each 30 minutes, filter, merging filtrate reclaims ethanol, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 3 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 40%, ethanol consumption eluting is 3 times of column volumes, collects eluent, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 80% alcohol reflux of 10 times of amounts 3 times, each 1.5 hours, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 2 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 60%, ethanol consumption eluting is 3 times of column volumes, collects eluent, after the drying again with the Herba Erigerontis extract mix homogeneously, add water for injection, and add 10% sodium chloride, stir evenly, cold preservation, filter, filtrate adds 0.1% active carbon, boils 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5～8.5, benefit adds to the full amount of water for injection, filtering with microporous membrane through 0.25～0.45 μ m, fill was sterilized 30 minutes, and was promptly got great transfusion preparation for 115 ℃.
Embodiments of the invention 5: Herba Erigerontis 190g, Radix Notoginseng 810g
Get Herba Erigerontis, add 60% alcohol reflux 2 times of 15 times of amounts, each 30 minutes, filter, merging filtrate reclaims ethanol, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 3 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 40%, ethanol consumption eluting is 3 times of column volumes, collects eluent, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 80% alcohol reflux of 10 times of amounts 3 times, each 1.5 hours, refining with D1 01 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 2 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 60%, and ethanol consumption eluting is 3 times of column volumes, collects eluent,, after the drying again with the Herba Erigerontis extract mix homogeneously, add water for injection, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 7.5～8.5, in medicinal liquid: it is caffolding agent that the ratio of caffolding agent=1: 3 adds dextran, and mixing is through the filtering with microporous membrane of 0.25～0.45 μ m, fill, lyophilization, lyophilisation condition :-10 ℃ of pre-freezes 3 hours ,-40 ℃ of pre-freezes began evacuation after 4 hours, and be warming up to-35 ℃, kept 2 hours; Be warming up to-30 ℃, kept 5 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to-10 ℃, kept 10 hours; Be warming up to 0 ℃, kept 2 hours; Be warming up to 10 ℃, kept 2 hours; Be warming up to 20 ℃, kept 2 hours; Be warming up to 30 ℃, kept 2 hours, promptly get lyophilized injectable powder.
Embodiments of the invention 6: Herba Erigerontis 190g, Radix Notoginseng 810g
Get Herba Erigerontis, add 60% alcohol reflux 2 times of 15 times of amounts, each 30 minutes, filter, merging filtrate reclaims ethanol, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 3 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 40%, ethanol consumption eluting is 3 times of column volumes, collects eluent, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 80% alcohol reflux of 10 times of amounts 3 times, each 1.5 hours, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 2 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 60%, and ethanol consumption eluting is 3 times of column volumes, collects eluent,, after the drying again with the Herba Erigerontis extract mix homogeneously, add water for injection, stir evenly, cold preservation filters, and filtrate adds 0.1% active carbon, boiled 30 minutes, put cold, be filtered to clear and bright, with 10%NaOH adjust pH 7.5～8.5, filtering with microporous membrane through 0.25～0.45 μ m, spray drying, packing promptly gets injectable powder.
Embodiments of the invention 7: Herba Erigerontis 180g, Radix Notoginseng 820g
Get Herba Erigerontis, add 60% alcohol reflux 2 times of 15 times of amounts, each 30 minutes, filter, merging filtrate reclaims ethanol, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 3 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 40%, ethanol consumption eluting is 3 times of column volumes, collects eluent, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 80% alcohol reflux of 10 times of amounts 3 times, each 1.5 hours, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 2 times of column volumes, and water consumption is 3 times of column volumes, ethanol elution concentration is 60%, ethanol consumption eluting is 3 times of column volumes, collects eluent, after the drying again with the Herba Erigerontis extract mix homogeneously, add water for injection, add 0.1% active carbon, boiled 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5～8.5, benefit adds to the full amount of water for injection, filtering with microporous membrane through 0.25～0.45 μ m, fill was sterilized 30 minutes, and was promptly got injection for 115 ℃.
Claims (10)
1, a kind of compound formulation of breviscapine for the treatment of cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to percentage by weight, it is made by Herba Erigerontis 15%～20% and Radix Notoginseng 80%～85%, or corresponding weight fraction Herba Erigerontis extract that obtains after extracting and the Radix Notoginseng extract that corresponding weight fraction obtains after extraction are made.
2, according to the compound formulation of breviscapine of the described this treatment cardiovascular and cerebrovascular disease of claim 1, it is characterized in that: calculate according to percentage by weight, it is made by Herba Erigerontis 18% and Radix Notoginseng 82%, or corresponding weight fraction Herba Erigerontis extract that obtains after extracting and the Radix Notoginseng extract that corresponding weight fraction obtains after extraction are made.
3, according to the compound formulation of breviscapine of claim 1 or 2 described this treatment cardiovascular and cerebrovascular diseases, it is characterized in that: described preparation is: injection comprises: all acceptable dosage forms on the pharmaceuticss such as injection, powder pin, freeze-dried powder, infusion solutions, dispersible tablet, tablet, capsule, soft capsule, microcapsule, granule, micropill, pill, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, soft extract, extractum and membrane.
4, according to the compound formulation of breviscapine of the described this treatment cardiovascular and cerebrovascular disease of claim 3, it is characterized in that: described preparation is: injection comprises: injection, powder pin, freeze-dried powder or infusion solutions.
5, as the preparation method of the compound formulation of breviscapine of any described treatment cardiovascular and cerebrovascular disease in the claim 1～4, it is characterized in that: get Herba Erigerontis, with 20%～80% alcohol reflux of 10～18 times of amounts 1～5 time, each 20～60 minutes, filter, merging filtrate, reclaim ethanol, refining with D101 type macroporous adsorbent resin, collect 10～60% ethanol elution, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 40～90% alcohol reflux of 8～12 times of amounts 1～5 time, each 1～3 hour, refining with D101 type macroporous adsorbent resin, collect 30%～80% ethanol elution, after the drying again with the Herba Erigerontis extract mix homogeneously, make different preparations then respectively.
6, according to the preparation method of the compound formulation of breviscapine of the described treatment cardiovascular and cerebrovascular disease of claim 5, it is characterized in that: get Herba Erigerontis, 60% alcohol reflux 2 times that adds 15 times of amounts, each 30 minutes, filter, merging filtrate, reclaim ethanol, refining with D101 type macroporous adsorbent resin, adsorption rate is the medicinal liquid that per hour passes through 3 times of column volumes, water consumption is 3 times of column volumes, ethanol elution concentration is 40%, and ethanol consumption eluting is 3 times of column volumes, collects eluent, drying promptly gets Herba Erigerontis extract; Get Radix Notoginseng, with 80% alcohol reflux of 10 times of amounts 3 times, each 1.5 hours, refining with D101 type macroporous adsorbent resin, adsorption rate was the medicinal liquid that per hour passes through 2 times of column volumes, water consumption is 3 times of column volumes, ethanol elution concentration is 60%, and ethanol consumption eluting is 3 times of column volumes, collects eluent, after the drying again with the Herba Erigerontis extract mix homogeneously, make different preparations then respectively.
7, according to the preparation method of the compound formulation of breviscapine of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Herba Erigerontis extract, Radix Notoginseng extract, add water for injection, and add 10% sodium chloride, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 7.5～8.5, benefit adds to the full amount of water for injection, through the filtering with microporous membrane of 0.25～0.45 μ m, fill, sterilized 30 minutes, and promptly got great transfusion preparation for 115 ℃.
8, preparation method according to the compound formulation of breviscapine of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Herba Erigerontis extract, Radix Notoginseng extract adds water for injection, stirs evenly, cold preservation, filter, filtrate adds 0.1% active carbon, boils 30 minutes, put cold, be filtered to clear and brightly, with 10%NaOH adjust pH 7.5～8.5, by medicinal liquid: the ratio adding dextran of caffolding agent=1: 3 is a caffolding agent, mixing, through the filtering with microporous membrane of 0.25～0.45 μ m, fill, lyophilization, lyophilisation condition :-10 ℃ of pre-freezes 3 hours,-40 ℃ of pre-freezes began evacuation after 4 hours, and were warming up to-35 ℃, kept 2 hours; Be warming up to-30 ℃, kept 5 hours; Be warming up to-20 ℃, kept 6 hours; Be warming up to-10 ℃, kept 10 hours; Be warming up to 0 ℃, kept 2 hours; Be warming up to 10 ℃, kept 2 hours; Be warming up to 20 ℃, kept 2 hours; Be warming up to 30 ℃, kept 2 hours, promptly get lyophilized injectable powder.
9, according to the preparation method of the compound formulation of breviscapine of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Herba Erigerontis extract, Radix Notoginseng extract, add water for injection, stir evenly, cold preservation filters, filtrate adds 0.1% active carbon, boils 30 minutes, puts cold, be filtered to clear and bright, with 10%NaOH adjust pH 7.5～8.5, through the filtering with microporous membrane of 0.25～0.45 μ m, spray drying, packing promptly gets injectable powder.
10, according to the preparation method of the compound formulation of breviscapine of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Herba Erigerontis extract, Radix Notoginseng extract, add water for injection, add 0.1% active carbon, boiled 30 minutes, and put coldly, be filtered to clear and bright, with 10%NaOH adjust pH 7.5～8.5, benefit adds to the full amount of water for injection, through the filtering with microporous membrane of 0.25～0.45 μ m, fill, sterilized 30 minutes, and promptly got injection for 115 ℃.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
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| CN 200410040869 CN1634255A (en) | 2004-10-15 | 2004-10-15 | Compound formulation of breviscapine for treating cardiovascular and cerebrovascular diseases and its preparing process |
| CN 200510200607 CN1768772A (en) | 2004-10-15 | 2005-10-13 | Compound formulation of breviscapine for treating cardiovascular and cerebrovascular diseases. its preparing process and application |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457768C (en) * | 2007-03-14 | 2009-02-04 | 樊献俄 | Preparation method of breviscapine raw material medicine by using big-hole resin |
| CN102940657A (en) * | 2012-10-31 | 2013-02-27 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
| CN105535057A (en) * | 2016-01-09 | 2016-05-04 | 王升云 | Composition capable of assisting in reduction of blood fat and preparing method, preparation and application thereof |
-
2004
- 2004-10-15 CN CN 200410040869 patent/CN1634255A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100457768C (en) * | 2007-03-14 | 2009-02-04 | 樊献俄 | Preparation method of breviscapine raw material medicine by using big-hole resin |
| CN102940657A (en) * | 2012-10-31 | 2013-02-27 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
| CN105535057A (en) * | 2016-01-09 | 2016-05-04 | 王升云 | Composition capable of assisting in reduction of blood fat and preparing method, preparation and application thereof |
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