CN1634489A - Medicine composition for treating cardiovascular and cerebrovascular diseases and preparation method thereof - Google Patents

Medicine composition for treating cardiovascular and cerebrovascular diseases and preparation method thereof Download PDF

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CN1634489A
CN1634489A CN 200410096630 CN200410096630A CN1634489A CN 1634489 A CN1634489 A CN 1634489A CN 200410096630 CN200410096630 CN 200410096630 CN 200410096630 A CN200410096630 A CN 200410096630A CN 1634489 A CN1634489 A CN 1634489A
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preparation
radix
extract
acanthopanacis senticosi
caulis acanthopanacis
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CN1310635C (en
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张平
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Abstract

Disclosed is a pharmaceutical composition for treating cardiovascular and cerebrovascular diseases, which is prepared fromacanthopanax root extract, gen-seng extract and medicinal adjuvant for water-soluble injection, and has the functions of benefiting vital energy, promoting blood circulation. The invention also discloses the process for preparing the pharmaceutical composition. Pharmacological experiment has shown that the medicinal composition has good actions for preventing and treating cardiovascular and cerebrovascular diseases.

Description

A kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof
Technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof, this pharmaceutical composition is referred to as the compound acanthopanax ejection preparation again.
Background technology
Cardiovascular and cerebrovascular disease is commonly encountered diseases, frequently-occurring disease clinically, in recent years, raising along with people's living standard, the age of onset of cardiovascular and cerebrovascular disease shifts to an earlier date to some extent, add the aging of population structure, its sickness rate is the trend that rises year by year, and the medicine of exploitation treatment cardiovascular and cerebrovascular disease gradually becomes the focus of research.Increasing clinical report shows that Chinese medicine is having a good application prospect aspect the treatment cardiovascular and cerebrovascular disease, and obtains people's attention day by day.
In the Chinese medicine of existing treatment cardiovascular and cerebrovascular disease, its prescription nearly all is that the medicine or the number flavor that have the blood circulation promoting and blood stasis dispelling function simply have the simple combination of activating blood circulation to dissipate blood stasis function medicament, and the effective ingredient in the medicine of making all has the effect of activating blood circulation to dissipate blood stasis.When using clinically, therapeutic effect may be obviously in a short time, and after the still long-time administration, effect improved meeting is more and more littler, and final therapeutic effect is not an ideal very.Each system of human body is the integral body of a complexity, is closely-related each other.The generation of cardiovascular and cerebrovascular disease is usually with the reduction of other systemic-function.If cardiovascular and cerebrovascular disease relies on the medicine of treatment cardiovascular and cerebrovascular disease to treat merely, just the symptom of blood circulation is improved, to very little of the improvement of other system of human body or even do not have, so just can not reach desired therapeutic effect for the treatment of patient disease.
Theory of Chinese medical science thinks that it is its main method of treatment that cardiovascular and cerebrovascular disease is worked as with blood stasis-eliminating and stagnation-dissipating, benefiting QI for activating blood circulation.QI invigorating is complementary with invigorating blood circulation." QI invigorating " can improve allomeric function, helps the carrying out of " invigorating blood circulation ", helps the elimination of angiemphraxis, increases blood supply of cardiac muscle, reduces myocardial infarct size and degree of injury, promotes the pathological changes reparation.
Radix Et Caulis Acanthopanacis Senticosi is dry root and rhizome or the stem or the leaf of Araliaceae Radix Et Caulis Acanthopanacis Senticosi, has the effect of blood circulation promoting and blood stasis dispelling, and wherein contained flavone compound is its main effective ingredient; The Araliaceae Radix Ginseng has the effect of strongly invigorating primordial QI, and wherein contained ginsenoside is its main effective ingredient.
In data-searching, find no any report with the pharmaceutical composition of Radix Et Caulis Acanthopanacis Senticosi, Radix Ginseng prescription.
Summary of the invention
We find under study for action, and Radix Et Caulis Acanthopanacis Senticosi extract and Radix Ginseng extract are share, and have " benefiting QI and nourishing blood, blood circulation and channel invigorating " function, the blood stasis dispelling circulation of qi promoting develops simultaneously, and based on blood stasis dispelling, the two action compensating, Synergistic has the better curative effect effect for cardiovascular and cerebrovascular disease.
The objective of the invention is to disclose a kind of Chinese medicine pharmaceutical composition.
Another object of the present invention is the preparation method that discloses aforementioned pharmaceutical compositions.
The present invention also provides the application of aforementioned pharmaceutical compositions in preparation treatment cardiovascular and cerebrovascular diseases medicament.
The present invention is achieved through the following technical solutions:
One, process recipes
(1) extract preparation
With the Radix Et Caulis Acanthopanacis Senticosi pulverizing medicinal materials, put into the supersound extraction jar, the ethanol water that adding 5-10 doubly measures 0%-80% carries out supersound extract, and frequency of oscillation is 20-100kHz, and the time is 20-90 minute, extracts 2-4 time, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 12000-20000 rev/min speed, and centrifugal liquid is the ultrafilter membrane ultrafiltration of 5000-10000 with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with the 10%-30% alcoholic solution eluting of 2-4 times of column volume, the 40%-70% alcoholic solution eluting of reuse 3-6 times column volume is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
The ginseng crude drug is pulverized, put into the supersound extraction jar, the ethanol water that adding 6-12 doubly measures 0%-80% carries out supersound extract, and frequency is 20-100kHz, and the time is 30-90 minute, extracts 2-4 time, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, speed with 12000-20000 rev/min is centrifugal, and centrifugal liquid is the ultrafilter membrane ultrafiltration of 5000-10000 with the molecular weight that dams, and filtrate is crossed the nonpolar or low pole macroporous adsorptive resins of having handled well, first water elution with 2-4 times of column volume, the ethanol elution of the 20%-80% of reuse 4-8 times column volume is collected ethanol elution and is recycled to nothing alcohol flavor, concentrate drying, pulverize, obtain Radix Ginseng extract.
(2) preparation of ejection preparation
The preparation of hydro-acupuncture preparation: above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 7-8 weight portion, Radix Ginseng extract 2-3 weight portion are merged, and with the water for injection dissolving, adjust pH is 4.5-6.0, filters sterilization, preparation cost invention compound acanthopanax hydro-acupuncture preparation.
The preparation of infusion preparation: above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 7-8 weight portion, Radix Ginseng extract 2-3 weight portion are merged,, add sodium chloride or glucose accent etc. and ooze with the water for injection dissolving, adjust pH is 4.5-6.0, filter sterilization, preparation cost invention compound acanthopanax infusion preparation.
The preparation of powder injection formulation: above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 7-8 weight portion, Radix Ginseng extract 2-3 weight portion are merged,, add excipient with the water for injection dissolving, adjust pH is 4.5-6.0, with 0.22 μ m filtering with microporous membrane, spray drying is packaged to be compound acanthopanax powder injection formulation of the present invention.
The preparation of freeze-dried powder: above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 7-8 weight portion, Radix Ginseng extract 2-3 weight portion are merged, dissolve with water for injection, add excipient, adjust pH is 4.5-6.0, with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be compound acanthopanax freeze-dried powder of the present invention.
Above-mentioned Radix Et Caulis Acanthopanacis Senticosi medical material has comprised root, rhizome, stem, the leaf of Radix Et Caulis Acanthopanacis Senticosi; Radix Et Caulis Acanthopanacis Senticosi extract can be one or more the extract in the root, rhizome, stem, leaf of Radix Et Caulis Acanthopanacis Senticosi.
Above-mentioned ginseng crude drug comprises Park Ginseng, SHANSHEN, Radix Ginseng Rubra, Folium Ginseng; Radix Ginseng extract can be one or more the extract in Park Ginseng, SHANSHEN, Radix Ginseng Rubra, the Folium Ginseng.
The ultrasonic wave energy that the sonic oscillation instrument produces produces judder, and is high-speed, intensive cavitation effect, and stirring action quickens the effective ingredient dissolving in the medical material, can improve the extraction rate of effective ingredient.The sonic oscillation equipment needed thereby is simple, easy to operate, extraction time is short, extraction ratio is high, energy-conservation, save medical material, need not heating, not only make the effective ingredient among Radix Et Caulis Acanthopanacis Senticosi and the ginseng crude drug keep stable completely simultaneously in extraction, and the amount of the impurity that extracts under the low temperature reduces greatly, makes follow-up enrichment and purification become and is more prone to.
Utilize the suitable ultrafilter membrane of molecular cut off, can remove macromolecular substances such as the tannin that makes ejection preparation rotten in the supersound extract liquid easily, protein, starch, make that the ejection preparation impurity content of making is few, good stability, effect duration be longer.
Polyamide has special affinity to the flavone compound in the Radix Et Caulis Acanthopanacis Senticosi medical material, utilizes this character to carry out enrichment and purification to the flavone compound in the acanthopanax senticosus extract.
Macroporous adsorbent resin has good adsorption to the ginsenoside.Utilize this character to carry out enrichment and purification to the saponin component among the Radix Ginseng extractive solution.
Two, assay analysis
The spectrophotography that the content of total flavone assay method is measured under the item according to Radix Et Caulis Acanthopanacis Senticosi injection (18 in Chinese medicine promulgated by the ministries or commissions of the Central Government) standard content in the Radix Et Caulis Acanthopanacis Senticosi is measured; The Determination of Total Saponin Content in Panax Ginseng method is according to list of references [Xu Suixu.Macroporous adsorbent resin-colorimetry is estimated content of ginsenoside in the Radix Ginseng.Shenyang Pharmacy College's journal, 1986,3 (2): 95] method in is carried out.Radix Et Caulis Acanthopanacis Senticosi injection is produced by the Chenxing Medical Industry Co Ltd, Jiamusi, Heilongjiang Prov, and specification is that 20ml/ props up (containing total flavones 100mg); 5 batches of compound acanthopanax ejection preparations of the present invention provide by Tianzhijiao Medication Development Co., Ltd., Guangdong.Measurement result sees Table 1.
The analysis of table 1 assay
Content
Lot number Radix Et Caulis Acanthopanacis Senticosi injection (mg/ props up) compound acanthopanax ejection preparation of the present invention (mg/ props up)
Total flavones total flavones total saponins
1 103.7 85.7 16.8
2 96.4 83.4 16.2
3 98.8 86.2 13.7
4 105.6 85.0 16.3
5 100.8 84.6 14.5
Annotate: the assay item is stipulated down in the Radix Et Caulis Acanthopanacis Senticosi injection quality standard: this product contains total flavones to be calculated by anhydrous rutin, should be the 90.0%-110.0% of labelled amount.
By above assay data as can be seen, the content of total flavone in the compound acanthopanax ejection preparation of the present invention is lower than Radix Et Caulis Acanthopanacis Senticosi injection; General flavone content in total flavones in the compound acanthopanax ejection preparation of the present invention and the content sum of total saponins and the Radix Et Caulis Acanthopanacis Senticosi injection is suitable.
Three, pharmacology embodiment
For the selection that proves absolutely preparation prescription of the present invention has science, reasonability, research worker of the present invention is contrast with commercially available Radix Et Caulis Acanthopanacis Senticosi injection, and preparation of the present invention has been carried out pharmacodynamic study.
In following experiment, being numbered of employed preparation of the present invention: 1, hydro-acupuncture preparation of the present invention, 2, infusion preparation of the present invention, 3, powder injection formulation of the present invention, 4, lyophilized injectable powder of the present invention, provide by Tianzhijiao Medication Development Co., Ltd., Guangdong; Radix Et Caulis Acanthopanacis Senticosi injection is produced by the Chenxing Medical Industry Co Ltd, Jiamusi, Heilongjiang Prov, and specification is that 20ml/ props up (containing total flavones 100mg).
1, the influence of anoxia in mice endurance is tested
Experimental technique: get 30 of healthy Kunming mouses, body weight 20-24g.Be divided into matched group at random, Radix Et Caulis Acanthopanacis Senticosi injection group, hydro-acupuncture preparation group of the present invention.Every group 10, male and female half and half, sub-cage rearing.With the conversion of people's conventional therapy dosage is the dosage of mice.The conversion formula is: tested animal is tried out the body surface area ratio of the body surface area ratio/known animal of dosage=known animals administer amount * tested animal.Control group administered physiological saline, 1 time/day, continuous 7d.1h after the last administration, it is the 150ml port grinding bottle that mice is placed volume respectively, in put the 15g sodica calx, its time-to-live of airtight observation.The results are shown in Table 2.
The influence of table 2 pair mice normobaric hypoxia (X ± SD)
Group Mus number (only) mean survival time (min)
Matched group 10 16.27 ± 3.97
Radix Et Caulis Acanthopanacis Senticosi injection group 10 29.36 ± 4.12 *
No. 1 group 10 33.55 ± 3.28 of the present invention *#
Annotate: compare with matched group: *P<0.01;
Compare with the Radix Et Caulis Acanthopanacis Senticosi injection group: #P<0.05.
Ejection preparation of the present invention, Radix Et Caulis Acanthopanacis Senticosi injection all can improve mice normobaric hypoxia endurance, and mean survival time is than matched group significant prolongation (P<0.01); Ejection preparation of the present invention is compared with Radix Et Caulis Acanthopanacis Senticosi injection, mean survival time also variant (P<0.05).Illustrate: the effect of ejection preparation of the present invention is better than Radix Et Caulis Acanthopanacis Senticosi injection.
2, to the anoxybiotic protective effect experiment of mouse cardiac muscle
Experimental technique: get 30 of healthy Kunming mouses, body weight 18-22g is divided into 3 groups at random, is divided into matched group at random, Radix Et Caulis Acanthopanacis Senticosi injection group, infusion preparation group of the present invention.Every group of male and female half and half, sub-cage rearing.With the conversion of people's conventional therapy dosage is the dosage of mice.The conversion formula is: tested animal is tried out the body surface area ratio of the body surface area ratio/known animal of dosage=known animals administer amount * tested animal.Control group administered physiological saline.Medication: 1 time/day, continuous 6 days.Back fixation was separated trachea with urethane 1.2g/kg intraperitoneal injection of anesthesia in 1 hour after the last administration, with the bulldog clamp folder pipe of holding one's breath, observed electrocardio with electrocardiogram equipment, and write down the little mousetrap with stopwatch and hold one's breath time of Guan Houzhi electrocardio disappearance.The results are shown in Table 3.
The anoxybiotic influence of table 3 pair mouse cardiac muscle (X ± SD)
Group Mus number (only) mean survival time (min)
Matched group 10 6.98 ± 0.85
Radix Et Caulis Acanthopanacis Senticosi injection group 10 12.37 ± 0.95 *
No. 2 groups 10 14.64 ± 0.78 of the present invention *#
Annotate: compare with matched group: *P<0.01;
Compare with the Radix Et Caulis Acanthopanacis Senticosi injection group: #P<0.05
Ejection preparation of the present invention, Radix Et Caulis Acanthopanacis Senticosi injection all can shield to the mouse cardiac muscle anoxia, and mean survival time is than matched group significant prolongation (P<0.01); Ejection preparation of the present invention is compared with Radix Et Caulis Acanthopanacis Senticosi injection, mean survival time also variant (P<0.05).Illustrate: the effect of ejection preparation of the present invention is better than Radix Et Caulis Acanthopanacis Senticosi injection.
3, the influence that the rat thrombus in vivo is formed
Rat is divided into 3 groups at random, 10 every group, is respectively normal saline matched group, Radix Et Caulis Acanthopanacis Senticosi injection group, powder injection formulation group of the present invention.With each treated animal administration (the normal saline group gives isopyknic normal saline), every day 1 time, successive administration 7 days, after the last administration 1 hour, rat is used 10% chloral hydrate, press 0.3g/kg body weight anesthesia back and fix, separate left common carotid artery, on the thrombosis instrument with 2mA galvanism blood vessel 7min after, the record thrombus formation time.The results are shown in Table 4.
The influence that table 4 pair rat thrombus in vivo forms (X ± SD)
Group Mus number (only) thrombus formation time (min)
Matched group 10 654.37 ± 78.46
Radix Et Caulis Acanthopanacis Senticosi injection group 10 778.24 ± 83.55 *
No. 3 groups 10 824.37 ± 75.83 of the present invention *#
Annotate: compare with matched group: *P<0.01;
Compare with the Radix Et Caulis Acanthopanacis Senticosi injection group: #P<0.05
Ejection preparation of the present invention and Radix Et Caulis Acanthopanacis Senticosi injection can both the prolong rats thrombus in vivo formation (P<0.01); Ejection preparation of the present invention is compared with Radix Et Caulis Acanthopanacis Senticosi injection, time expand also variant (P<0.05).Illustrate: the effect of ejection preparation of the present invention is better than Radix Et Caulis Acanthopanacis Senticosi injection.
4, to the thrombotic influence of rats in vitro
Rat is divided into 3 groups at random, 10 every group, is respectively normal saline matched group, Radix Et Caulis Acanthopanacis Senticosi injection, lyophilized injectable powder group of the present invention.With each treated animal administration, every day 1 time, successive administration 7 days after the last administration 1 hour, is fixed rat anesthesia, from abdominal aortic blood 1.8ml, at once put into silica gel tube, and put it in the extracorporeal thrombosis forming device of 37 ℃ of constant temperature, rotate 15min after, removal of thromboses is measured its length, weight in wet base and dry weight.The results are shown in Table 5.
The thrombotic influence of table 5 pair rats in vitro (X ± SD)
Thrombosis length wet weight of thrombus thrombosis dry weight
Group
(l/cm) (m/g) (m/g)
Matched group 6.83 ± 0.78 0.325 ± 0.064 0.188 ± 0.064
Radix Et Caulis Acanthopanacis Senticosi injection group 5.54 ± 0.85 *0.278 ± 0.057 *0.142 ± 0.056 *
No. 4 groups 5.22 ± 0.84 of the present invention *# 0.245 ± 0.062 *# 0.128 ± 0.052 *#
Annotate: compare with matched group: *P<0.01;
Compare with the Radix Et Caulis Acanthopanacis Senticosi injection group: #P<0.05.
Ejection preparation of the present invention and Radix Et Caulis Acanthopanacis Senticosi injection can both obviously shorten external thrombus and form length, reduce the weight in wet base and the dry weight (P<0.01) of thrombosis; Ejection preparation of the present invention is compared with Radix Et Caulis Acanthopanacis Senticosi injection, also variant (P<0.05).Illustrate: ejection preparation effect of the present invention is better than oral liquid of acanthopanax bark.
5, antiplatelet aggregative activity
Rat is divided into 3 groups at random, 10 every group, is respectively matched group, Radix Et Caulis Acanthopanacis Senticosi injection group, lyophilized injectable powder group of the present invention.Each treated animal administration, every day 1 time, successive administration 7 days, after the last administration 1 hour, from abdominal aortic blood, anticoagulant adopted 3.28% sodium citrate after the Animal Anesthesia, with blood with 1: 9 mixed.With anticoagulated whole blood 1500rmin under 20 ℃ of conditions -1Centrifugal 5min, and the acquisition platelet rich plasma (platelet-richplasma, PRP).After leaving and taking quantitative PRP, will remain PRP once more with 3000rmin -1Centrifugal 10min, and acquisition own control platelet poor plasma (platelet-poorplasma, PPP).Regulate PRP concentration with PPP, make each PRP concentration identical.In 37 ℃ constant temperature hole after the preheating, (final concentration is 3 μ molL to add ADP with PRP -1) cause and write down maximum agglutination rate by platelet aggregation.The results are shown in Table 6.
Table 6 antiplatelet aggregative activity (X ± SD)
Group Mus number (only) maximum agglutination rate (η/%)
Matched group 10 93.46 ± 15.26
Radix Et Caulis Acanthopanacis Senticosi injection group 10 72.83 ± 17.64 *
No. 4 groups 10 63.54 ± 15.33 of the present invention *#
Annotate: compare with matched group: *P<0.01;
Compare with the Radix Et Caulis Acanthopanacis Senticosi injection group: #P<0.05
Ejection preparation of the present invention and Radix Et Caulis Acanthopanacis Senticosi injection be anticoagulant (P<0.01) obviously; Ejection preparation of the present invention is compared with Radix Et Caulis Acanthopanacis Senticosi injection, also variant (P<0.05).Illustrate: the effect of ejection preparation of the present invention is better than Radix Et Caulis Acanthopanacis Senticosi injection.
Above pharmacological evaluation proves, of the present invention is that the compound acanthopanax ejection preparation of raw material prescription has great pharmacological effects by Radix Et Caulis Acanthopanacis Senticosi extract and Radix Ginseng extract.Explanation thus has the effect of excellent prevention and treatment cardiovascular and cerebrovascular disease according to the theory of Chinese medical science prescription of " benefiting QI and nourishing blood, blood circulation and channel invigorating ", the compound acanthopanax ejection preparation that utilizes preparation method of the present invention to make.
Four, preparation embodiment
Following examples are intended to further illustrate, rather than restriction the present invention.Under the prerequisite of the spirit and principles in the present invention, will fall in the claim scope of the present invention inventing any change that indivedual technical steps carry out or changing.
Embodiment 1
Caulis Et Caulis Acanthopanacis Senticosi is pulverized, put into the supersound extraction jar, the water that adds 10 times of amounts carries out supersound extract, and frequency of oscillation is 20kHz, and the time is 90 minutes, extracts 4 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 12000 rev/mins speed, and centrifugal liquid is 5000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 10% alcoholic solution eluting of 4 times of column volumes, 70% alcoholic solution eluting of 3 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
Park Ginseng is pulverized, put into the supersound extraction jar, the water that adds 6 times of amounts carries out supersound extract, and frequency is 100kHz, and the time is 30 minutes, extracts 2 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, and filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 20000 rev/mins speed, and centrifugal liquid is 10000 ultrafilter membrane ultrafiltration with the molecular weight that dams, and filtrate is crossed the D that has handled well 101The type macroporous adsorptive resins, earlier with the water elution of 2 times of column volumes, 20% ethanol elution of 8 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have the alcohol flavor, concentrate, drying, pulverizing obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 70g, Radix Ginseng extract 30g and merge, with the water for injection dissolving, adjust pH is 6.0, filters sterilization, 500 of preparation cost invention compound acanthopanax hydro-acupuncture preparations.
Embodiment 2
The Radix Et Caulis Acanthopanacis Senticosi rhizome is pulverized, put into the supersound extraction jar, 80% alcoholic solution that adds 5 times of amounts carries out supersound extract, and frequency of oscillation is 100kHz, and the time is 20 minutes, extracts 2 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 20000 rev/mins speed, and centrifugal liquid is 10000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 30% alcoholic solution eluting of 2 times of column volumes, 40% alcoholic solution eluting of 6 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
Park Ginseng and Radix Ginseng Rubra are pulverized, put into the supersound extraction jar, 80% alcoholic solution that adds 12 times of amounts carries out supersound extract, and frequency is 20kHz, and the time is 90 minutes, extracts 4 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 12000 rev/mins speed, and centrifugal liquid is 5000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the AB-8 type macroporous adsorptive resins of having handled well, earlier with the water elution of 4 times of column volumes, 80% ethanol elution of 4 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have alcohol and distinguish the flavor of, concentrate, drying is pulverized, and obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 80g, Radix Ginseng extract 20g, with the water for injection dissolving, adding sodium chloride accent etc. oozes, and adjust pH is 4.5, filters sterilization, 500 bottles of preparation cost invention compound acanthopanax infusion preparations.
Embodiment 3
Radix Acanthopanacis Senticosi root is pulverized, put into the supersound extraction jar, 20% the ethanol that adds 8 times of amounts carries out supersound extract, and frequency of oscillation is 50kHz, and the time is 40 minutes, extracts 3 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 18000 rev/mins speed, and centrifugal liquid is 6500 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 20% alcoholic solution eluting of 3 times of column volumes, 60% alcoholic solution eluting of 4 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
SHANSHEN and Folium Ginseng are pulverized, put into the supersound extraction jar, 50% the ethanol that adds 10 times of amounts carries out supersound extract, and frequency is 60kHz, and the time is 50 minutes, extracts 3 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 15000 rev/mins speed, and centrifugal liquid is 8000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the NKA type macroporous adsorptive resins of having handled well, earlier with the water elution of 2 times of column volumes, 50% ethanol elution of 6 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have alcohol and distinguish the flavor of, concentrate, drying is pulverized, and obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 75g, Radix Ginseng extract 25g, with the water for injection dissolving, adding glucose accent etc. oozes, and adjust pH is 5.0, filters sterilization, 500 bottles of preparation cost invention compound acanthopanax infusion preparations.
Embodiment 4
Folium Acanthopanacis Senticosi is pulverized, put into the supersound extraction jar, 60% the ethanol that adds 6 times of amounts carries out supersound extract, and frequency of oscillation is 40kHz, and the time is 70 minutes, extracts 2 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 14000 rev/mins speed, and centrifugal liquid is 8000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 15% alcoholic solution eluting of 2 times of column volumes, 50% alcoholic solution eluting of 5 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
SHANSHEN and Radix Ginseng Rubra are pulverized, put into the supersound extraction jar, 70% the ethanol that adds 8 times of amounts carries out supersound extract, and frequency is 80kHz, and the time is 60 minutes, extracts 4 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, and filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 14000 rev/mins speed, and centrifugal liquid is 6000 ultrafilter membrane ultrafiltration with the molecular weight that dams, and filtrate is crossed the D that has handled well 101The type macroporous adsorptive resins, earlier with the water elution of 3 times of column volumes, 40% ethanol elution of 5 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have the alcohol flavor, concentrate, drying, pulverizing obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 73g, Radix Ginseng extract 27g and merge,, add polyvinylpyrrolidone 200g with the water for injection dissolving, adjust pH is 5.5, with 0.22 μ m filtering with microporous membrane, spray drying is packaged to be 500 of compound acanthopanax powder injection formulations of the present invention.
Embodiment 5
Radix Et Caulis Acanthopanacis Senticosi rhizome and root are pulverized, put into the supersound extraction jar, 40% the ethanol that adds 7 times of amounts carries out supersound extract, and frequency of oscillation is 80kHz, and the time is 30 minutes, extracts 4 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 15000 rev/mins speed, and centrifugal liquid is 7400 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 25% alcoholic solution eluting of 4 times of column volumes, 45% alcoholic solution eluting of 4 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
Radix Ginseng Rubra is pulverized, put into the supersound extraction jar, 30% the ethanol that adds 9 times of amounts carries out supersound extract, and frequency is 40kHz, and the time is 40 minutes, extracts 2 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, and filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 18000 rev/mins speed, and centrifugal liquid is 9000 ultrafilter membrane ultrafiltration with the molecular weight that dams, and filtrate is crossed the D that has handled well 101The type macroporous adsorptive resins, earlier with the water elution of 4 times of column volumes, 70% ethanol elution of 7 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have the alcohol flavor, concentrate, drying, pulverizing obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 77g, Radix Ginseng extract 23g and merge,, add mannitol and dextran 200g altogether with the water for injection dissolving, adjust pH is 4.8, with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 500 of compound acanthopanax freeze-dried powders of the present invention.
Embodiment 6
Caulis Et Caulis Acanthopanacis Senticosi and rhizome are pulverized, put into the supersound extraction jar, 50% the ethanol that adds 9 times of amounts carries out supersound extract, and frequency of oscillation is 60kHz, and the time is 50 minutes, extracts 3 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 16000 rev/mins speed, and centrifugal liquid is 9000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 18% alcoholic solution eluting of 3 times of column volumes, 65% alcoholic solution eluting of 6 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
Radix Ginseng Rubra and SHANSHEN and Park Ginseng are pulverized, put into the supersound extraction jar, 40% the ethanol that adds 7 times of amounts carries out supersound extract, and frequency is 50kHz, and the time is 45 minutes, extracts 3 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 16000 rev/mins speed, and centrifugal liquid is 7000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the AB-8 type macroporous adsorptive resins of having handled well, earlier with the water elution of 3 times of column volumes, 30% ethanol elution of 5 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have alcohol and distinguish the flavor of, concentrate, drying is pulverized, and obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 74g, Radix Ginseng extract 26g and merge,, add polyvinylpyrrolidone and lactose 200g altogether with the water for injection dissolving, adjust pH is 5.3, with 0.22 μ m filtering with microporous membrane, spray drying is packaged to be 500 of compound acanthopanax powder injection formulations of the present invention.
Embodiment 7
Folium Acanthopanacis Senticosi and root are pulverized, put into the supersound extraction jar, 30% the ethanol that adds 6 times of amounts carries out supersound extract, and frequency of oscillation is 70kHz, and the time is 60 minutes, extracts 2 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, and filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 16000 rev/mins speed, and centrifugal liquid is 5500 ultrafilter membrane ultrafiltration with the molecular weight that dams, and filtrate is crossed the polyamide column of having handled well.With 23% alcoholic solution eluting of 2 times of column volumes, 58% alcoholic solution eluting of 5 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor, concentrates earlier, and drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
Radix Ginseng Rubra and Folium Ginseng are pulverized, put into the supersound extraction jar, 30% the ethanol that adds 11 times of amounts carries out supersound extract, and frequency is 30kHz, and the time is 70 minutes, extracts 3 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, and filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 13000 rev/mins speed, and centrifugal liquid is 6500 ultrafilter membrane ultrafiltration with the molecular weight that dams, and filtrate is crossed the D that has handled well 101The type macroporous adsorptive resins, earlier with the water elution of 2 times of column volumes, 60% ethanol elution of 4 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have the alcohol flavor, concentrate, drying, pulverizing obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 72g, Radix Ginseng extract 28g and merge, with the water for injection dissolving, add lactose 200g, adjust pH is 5.7, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 500 of compound acanthopanax freeze-dried powders of the present invention.
Embodiment 8
Caulis Et Caulis Acanthopanacis Senticosi is broken, put into the supersound extraction jar, the water that adds 8 times of amounts carries out supersound extract, and frequency of oscillation is 55kHz, and the time is 80 minutes, extracts 3 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 17000 rev/mins speed, and centrifugal liquid is 5000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 30% alcoholic solution eluting of 4 times of column volumes, 40% alcoholic solution eluting of 3 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
SHANSHEN is pulverized, put into the supersound extraction jar, 80% the ethanol that adds 6 times of amounts carries out supersound extract, and frequency is 95kHz, and the time is 85 minutes, extracts 4 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 19000 rev/mins speed, and centrifugal liquid is 8500 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the AB-8 type macroporous adsorptive resins of having handled well, earlier with the water elution of 4 times of column volumes, 80% ethanol elution of 2 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have alcohol and distinguish the flavor of, concentrate, drying is pulverized, and obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 79g, Radix Ginseng extract 21g and merge, with the water for injection dissolving, add mannitol 200g, adjust pH is 5.2, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 500 of compound acanthopanax freeze-dried powders of the present invention.
Embodiment 9
Folium Acanthopanacis Senticosi is pulverized, put into the supersound extraction jar, 30% the ethanol that adds 5 times of amounts carries out supersound extract, and frequency of oscillation is 30kHz, and the time is 50 minutes, extracts 4 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 13000 rev/mins speed, and centrifugal liquid is 10000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 10% alcoholic solution eluting of 3 times of column volumes, 70% alcoholic solution eluting of 6 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
With Park Ginseng and SHANSHEN and Folium Ginseng pulverizing, put into the supersound extraction jar, the water that adds 12 times of amounts carries out supersound extract, and frequency is 35kHz, and the time is 75 minutes, extracts 2 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 14000 rev/mins speed, and centrifugal liquid is 7000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the NKA type macroporous adsorptive resins of having handled well, earlier with the water elution of 3 times of column volumes, 20% ethanol elution of 5 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have alcohol and distinguish the flavor of, concentrate, drying is pulverized, and obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 78g, Radix Ginseng extract 22g, with the water for injection dissolving, adding sodium chloride accent etc. oozes, and adjust pH is 4.6, filters sterilization, 500 bottles of preparation cost invention compound acanthopanax infusion preparations.
Embodiment 10
Radix Acanthopanacis Senticosi root is pulverized, put into the supersound extraction jar, 45% the ethanol that adds 10 times of amounts carries out supersound extract, and frequency of oscillation is 75kHz, and the time is 30 minutes, extracts 2 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 15000 rev/mins speed, and centrifugal liquid is 8000 ultrafilter membrane ultrafiltration with the molecular weight that dams, filtrate is crossed the polyamide column of having handled well, with 18% alcoholic solution eluting of 2.5 times of column volumes, 50% alcoholic solution eluting of 5 times of column volumes of reuse is collected ethanol elution and is recycled to nothing alcohol flavor earlier, concentrate, drying is pulverized, and obtains Radix Et Caulis Acanthopanacis Senticosi extract.
Park Ginseng and SHANSHEN and Radix Ginseng Rubra and Folium Ginseng are pulverized, put into the supersound extraction jar, 45% the ethanol that adds 10 times of amounts carries out supersound extract, and frequency is 35kHz, and the time is 65 minutes, extracts 2 times, and the control temperature is a room temperature; Merge extractive liquid, leaves standstill, and filters, and filtrate decompression is concentrated into solution: medical material is 1: 1, and is centrifugal with 12000 rev/mins speed, and centrifugal liquid is 5000 ultrafilter membrane ultrafiltration with the molecular weight that dams, and filtrate is crossed the D that has handled well 101The type macroporous adsorptive resins, earlier with the water elution of 3 times of column volumes, 55% ethanol elution of 3 times of column volumes of reuse is collected ethanol elution and is recycled to and does not have the alcohol flavor, concentrate, drying, pulverizing obtains Radix Ginseng extract.
Get above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract 71g, Radix Ginseng extract 29g and merge, with the water for injection dissolving, adjust pH is 5.8, filters sterilization, 500 of preparation cost invention compound acanthopanax hydro-acupuncture preparations.
Ejection preparation intravenous drip of the present invention, one time 3-5 props up, 1-2 time on the one.

Claims (10)

1, a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease is characterized in that this pharmaceutical composition is that Radix Ginseng extract 2-3 weight portion and water soluble parenteral solution are prepared from medicinal adjuvant by Radix Et Caulis Acanthopanacis Senticosi extract 7-8 weight portion; Its feature is that also this medicine is an ejection preparation, comprises aqueous injection, infusion solution, injectable powder and lyophilized injectable powder.
2, preparation of drug combination method according to claim 1 is characterized in that may further comprise the steps:
(1) with the Radix Et Caulis Acanthopanacis Senticosi pulverizing medicinal materials, the polar solvent of doubly measuring with 5-10 extracts 2-4 time, each 20-90 minute, merge extractive liquid,, leave standstill, filter, filtrate decompression is concentrated into solution: medical material is 1: 1, high speed centrifugation, centrifugal liquid ultrafilter membrane ultrafiltration, filtrate is crossed the polyamide column of having handled well, first 10%-30% alcoholic solution eluting with 2-4 times of column volume, the 40%-70% alcoholic solution eluting of reuse 3-6 times column volume, collect ethanol elution and be recycled to nothing alcohol flavor, concentrate drying, pulverize, obtain above-mentioned Radix Et Caulis Acanthopanacis Senticosi extract;
(2) ginseng crude drug is pulverized, the polar solvent of doubly measuring with 6-12 extracts 2-4 time, each 20-90 minute, merge extractive liquid, leaves standstill, and filters, filtrate decompression is concentrated into solution: medical material is 1: 1, high speed centrifugation, centrifugal liquid ultrafilter membrane ultrafiltration, filtrate is crossed the macroporous adsorptive resins of having handled well, first water elution with 1-3 times of column volume, the ethanol elution of the 20%-80% of reuse 4-8 times column volume, collect ethanol elution and be recycled to nothing alcohol flavor, concentrate drying, pulverize, obtain above-mentioned Radix Ginseng extract.
3, preparation of drug combination method according to claim 2 is characterized in that, extracting method is a supersound extract.
4, preparation of drug combination method according to claim 3 is characterized in that, the frequency of oscillation of supersound extract is 20-100kHz.
5, preparation of drug combination method according to claim 2 is characterized in that, polar solvent is the ethanol water of 0%-80%.
6, preparation of drug combination method according to claim 2 is characterized in that, centrifugal speed is 12000-20000 rev/min.
7, preparation of drug combination method according to claim 2 is characterized in that, the molecular cut off of ultrafilter membrane is 5000-10000.
8, preparation of drug combination method according to claim 2 is characterized in that, macroporous adsorbent resin is nonpolar or low pole.
9, preparation of drug combination method according to claim 1 is characterized in that may further comprise the steps.
The preparation of hydro-acupuncture preparation: Radix Et Caulis Acanthopanacis Senticosi extract, the Radix Ginseng extract of above-mentioned weight portion are merged, and with the water for injection dissolving, adjust pH is 4.5-6.0, filters, and sterilization is prepared into hydro-acupuncture preparation;
The preparation of infusion preparation: Radix Et Caulis Acanthopanacis Senticosi extract, the Radix Ginseng extract of above-mentioned weight portion are merged, with the water for injection dissolving, add sodium chloride or glucose accent etc. and ooze, adjust pH is 4.5-6.0, filters, and sterilization is prepared into infusion preparation;
The preparation of powder injection formulation: Radix Et Caulis Acanthopanacis Senticosi extract, the Radix Ginseng extract of above-mentioned weight portion are merged, with the water for injection dissolving, add excipient, adjust pH is 4.5-6.0, and with 0.22 μ m filtering with microporous membrane, spray drying is packaged to be powder injection formulation;
The preparation of freeze-dried powder: Radix Et Caulis Acanthopanacis Senticosi extract, the Radix Ginseng extract of above-mentioned weight portion are merged, with the water for injection dissolving, add excipient, adjust pH is 4.5-6.0, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be freeze-dried powder.
10, the application of pharmaceutical composition according to claim 1 in preparation treatment cardiovascular and cerebrovascular diseases medicament.
CNB200410096630XA 2004-12-03 2004-12-03 Medicine composition for treating cardiovascular and cerebrovascular diseases and preparation method thereof Expired - Fee Related CN1310635C (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103239493A (en) * 2013-05-27 2013-08-14 北华大学 Pharmaceutical composition for reducing blood sugar and preparation method thereof
CN105193886A (en) * 2014-06-25 2015-12-30 北华大学 Preparation method and medical application of blood-fat-reducing active component
CN105285268A (en) * 2015-11-30 2016-02-03 黑龙江北秀健康产业有限公司 Health protection tea for preventing and treating cardiovascular and cerebrovascular diseases

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Publication number Priority date Publication date Assignee Title
CN1066600A (en) * 1992-07-03 1992-12-02 刘长海 The preparation method of dual ginsengs tonic health medicine for taken with mixed in water instautly

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103239493A (en) * 2013-05-27 2013-08-14 北华大学 Pharmaceutical composition for reducing blood sugar and preparation method thereof
CN105193886A (en) * 2014-06-25 2015-12-30 北华大学 Preparation method and medical application of blood-fat-reducing active component
CN105285268A (en) * 2015-11-30 2016-02-03 黑龙江北秀健康产业有限公司 Health protection tea for preventing and treating cardiovascular and cerebrovascular diseases
CN105285268B (en) * 2015-11-30 2019-02-19 黑龙江北秀健康产业有限公司 A kind of prevention and treatment cardiovascular and cerebrovascular disease health protection tea

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