CN1868508B - Medicine composition, application of the same for preparing medicine to treat and prevent cardiovascular and cerebrovascular disease - Google Patents
Medicine composition, application of the same for preparing medicine to treat and prevent cardiovascular and cerebrovascular disease Download PDFInfo
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Abstract
A medicinal composition used to prepare the medicines for preventing and treating cardiovascular and cerebrovascular diseases contains danshinolic acid and paeoniflorin in ratio of (1-5): (5-1). Its preparing process is also disclosed.
Description
Technical field:
The present invention relates to a kind of pharmaceutical composition and its production and use, relating to salvianolic acid and Radix Paeoniae Alba total glycosides particularly is pharmaceutical composition of active component and its production and use.
Background technology:
Salvianolic acid extracts acquisition from Radix Salviae Miltiorrhizae, its main component is salvianolic acid B, rosmarinic acid, danshensu, protocatechualdehyde etc.Salvianolic acid aspect cardiovascular and cerebrovascular disease, all have the certain protection effect [Ren Decheng, Du Guanhua, Zhang Juntian. total salvianolic acid is to the protective effect of cerebral ischemia reperfusion injury. Chinese Pharmacological circular, 2002,18 (3): 275～277.; Xu Jiangping, Sun Lisha, Wu Hangyu, etc. salvianolic acid B is to the protective effect of rat heart muscle ischemia reperfusion injury. Chinese Pharmaceutical Journal, 2003,38 (8): 595～597].
Peoniflorin (Paeoniflorin) is mainly derived from medical materials such as medical material Radix Paeoniae Rubra, the Radix Paeoniae Alba, Cortex Moutan, is its main effective ingredient.Report such as Wei Shoujian paeoniflorin is to the protection and the Mechanism Study [Chinese tcm emergency, 2000,9 (6): 274-276.] of PC12 cell ischemia injury; Zhang Guangqin etc. think that peoniflorin is to the blocking effect of rat myocardial cell L calcium channel [Chinese Pharmacological circular, 2003,19 (8): 863-866.]; Yang Jun etc. have reported the protective effect [Chinese Journal of New Drugs of peoniflorin to potassium chloride and the inductive PC12 cell calcium overload of N-methyl D-Aspartic Acid damage, 2001,10 (6): 426-428.] Yang Jun has carried out studying [Medical University Of Anhui's journal to Radix Paeoniae Rubra total glycosides treatment ischemic cerebrovascular effect and mechanism thereof, 2001,36 (2): 164.]; Xu Hongmei has reported total paeony glycoside anti thrombotic action [Anhui Chinese Medicine College journal, 2000,19 (1): 46-47.].
The inventor is by a large amount of experimentatioies, and having invented a kind of is the pharmaceutical composition of active component with salvianolic acid and Radix Paeoniae Alba total glycosides, and then the application of this pharmaceutical composition in the medicine of preparation treatment or prevention cardiovascular and cerebrovascular disease is provided.
Summary of the invention:
The invention provides a kind of is the pharmaceutical composition of active component with salvianolic acid extract and extract of total glucosides of paeony, 100%＞salvianolic acid (in danshensu) content 〉=50% in the salvianolic acid extract wherein, be preferably 100%＞content of Danshensu 〉=80%, 100%＞Radix Paeoniae Alba total glycosides content 〉=50% in the extract of total glucosides of paeony, 100%＞paeoniflorin content 〉=40%, be preferably 100%＞Radix Paeoniae Alba total glycosides content 〉=80%, 100%＞paeoniflorin content 〉=60%, the portion rate of salvianolic acid extract and extract of total glucosides of paeony is 1: 9～9: 1, is preferably 1: 5～5: 1.
The invention provides the preparation method of aforementioned pharmaceutical compositions.
The invention provides the application of aforementioned pharmaceutical compositions in the medicine of preparation treatment or prevention cardiovascular and cerebrovascular disease.
The invention provides the application of aforementioned pharmaceutical compositions in preparing medicines such as treatment or prevention coronary heart disease, angina pectoris, cardiac-cerebral ischemia.
Pharmaceutical composition provided by the invention contains active component 60mg～6000mg, is preferably 60mg～1800mg.
Pharmaceutical composition of the present invention, wherein the salvianolic acid extract can by but be not limited to from red rooted salvia, extract; Extract of total glucosides of paeony can by but be not limited to from Cortex Moutan, Radix Paeoniae Rubra or the Radix Paeoniae Alba, extract.
The pharmaceutical composition that the present invention proposes can be injection, injectable powder, tablet, capsule, granule, oral liquid, microgranule, preferred lyophilized injectable powder, and used adjuvant is the conventional adjuvant of various preparations.
Pharmaceutical composition provided by the invention is when being used for cardiovascular and cerebrovascular disease, and its using dosage scope is 60mg～6000mg, is preferably 60mg～2000mg.
The salvianolic acid extract that the present invention proposes can by but be not limited to following method and make: get red rooted salvia, water logging bubble post-heating extracts, filter the back merging filtrate, concentrate back dilute sulfuric acid acid precipitation, centrifugal and precipitation separation, precipitation is regulated pH value with sodium hydroxide solution and is made its dissolving, adsorbs by macroporous adsorptive resins.With the pure water eluting, again with the alcoholic solution eluting, collect eluent earlier, concentrating under reduced pressure is regulated pH value and is made with extra care, and promptly gets salvianolic acid after the concentrated solution lyophilizing.
Extract of total glucosides of paeony provided by the invention can by but be not limited to following method and make: get the Cortex Moutan pulverizing medicinal materials, water heating extraction 2 times is filtered, cooling is adsorbed with macroporous adsorbent resin, and water fully is eluted to effluent for after clarification and not having reducing sugar reaction, reuse Diluted Alcohol eluant solution, collect eluent, concentrating under reduced pressure is closely dried, and reuse ethanol is refining, filter, reclaim ethanol, polyamide chromatography column purification is drying to obtain extract of total glucosides of paeony on the concentrated solution.
The inventor has confirmed with salvianolic acid extract and extract of total glucosides of paeony to be the application of pharmaceutical composition in the medicine of preparation treatment or prevention cardiovascular and cerebrovascular disease of active component by following test, and its effect far is better than and singly uses with dosage salvianolic acid extract or extract of total glucosides of paeony.
Concrete embodiment:
Preparation example 1: preparation salvianolic acid extract and extract of total glucosides of paeony
Get red rooted salvia 10kg, water logging bubble heating extraction secondary with 12 times of amounts, filter the back merging filtrate, concentrate back with 10% sulphuric acid acid precipitation, centrifugal and precipitation separation, precipitation is regulated pH value with sodium hydroxide solution and is made its dissolving, according to passing through the D101 macroporous adsorptive resins than adsorbance 1: 1 (amount of resin and medical material amount), promptly uses 20kg macroporous resin packed column.With 5 times of volume pure water eluting, again with 10 times of column volume eluting of 30% alcoholic solution, collect eluent earlier, concentrating under reduced pressure is removed ethanol, regulates pH value and makes with extra care, and concentrated solution obtains the loose crystal type powder of pale brown color through lyophilizing, and wherein content of Danshensu is 54%.
Get 10kg Cortex Moutan pulverizing medicinal materials, 10 times of water gaging heating extraction 2 times are filtered, cooling is adsorbed with macroporous adsorbent resin, and water fully is eluted to effluent for after clarification and not having reducing sugar reaction, reuse Diluted Alcohol eluant solution is collected eluent, and concentrating under reduced pressure is closely dried, reuse ethanol is refining, filters, and reclaims ethanol, polyamide chromatography column purification on the concentrated solution, the dry extract of total glucosides of paeony that gets, wherein Radix Paeoniae Alba total glycosides (in peoniflorin) content is 65%, paeoniflorin content is 57%.
Preparation example 2: preparation salvianolic acid extract and extract of total glucosides of paeony
Get red rooted salvia 10kg, water logging bubble heating extraction secondary with 12 times of amounts, filter the back merging filtrate, concentrate back with 10% sulphuric acid acid precipitation, centrifugal and precipitation separation, precipitation is regulated pH value with sodium hydroxide solution and is made its dissolving, according to passing through the AB-8 macroporous adsorptive resins than adsorbance 1: 1 (amount of resin and medical material amount), promptly uses 20kg macroporous resin packed column.With 10 times of volume deionized-distilled water eluting, collect eluent, concentrating under reduced pressure is regulated pH value and is made with extra care, and concentrated solution obtains the loose crystal type powder of pale brown color through lyophilizing, and wherein content of Danshensu is 82%.
Get 10kg Cortex Moutan pulverizing medicinal materials, 10 times of water gaging heating extraction 2 times, filter, cooling, adsorb with 4 times of amounts (amount of resin and medical material amount) macroporous adsorbent resin, water fully is eluted to effluent for after clarification and not having reducing sugar reaction, and reuse 40% alcoholic solution eluting is collected eluent, concentrating under reduced pressure is closely dried, reuse 80% ethanol is refining, filters, and reclaims ethanol, polyamide chromatography column purification on the concentrated solution, the dry extract of total glucosides of paeony that gets, wherein Radix Paeoniae Alba total glycosides (in peoniflorin) content is 84%, paeoniflorin content is 76%.
Preparation example 3: preparation is the freeze-dried powder of active component with salvianolic acid extract and extract of total glucosides of paeony
Get salvianolic acid extract (content of Danshensu is 82%) 30g, (Radix Paeoniae Alba total glycosides is 84% in peoniflorin content to extract of total glucosides of paeony, wherein paeoniflorin content is 76%) 30g adds injection water 2000ml after mixing, with mannitol 8g, stirring and dissolving, ultrafiltration, obtain apyrogenic clear liquor, pour in the 10ml cillin bottle, 2ml/ only, press the lyophilizing of freeze-dried powder technology, make freeze-dried powder.
Get salvianolic acid extract (content of Danshensu is 54%) 30g, (in peoniflorin Radix Paeoniae Alba total glycosides content is 65% to extract of total glucosides of paeony, wherein paeoniflorin content is 57%) 30g adds injection water 2000ml after mixing, with mannitol 8g, stirring and dissolving, ultrafiltration, obtain apyrogenic clear liquor, pour in the 10ml cillin bottle, 2ml/ only, press the lyophilizing of freeze-dried powder technology, make freeze-dried powder.
Test example 1: pharmaceutical composition of the present invention is to the influence of rat heart muscle ischemic injuries
(1) material:
Salvianolic acid extract, extract of total glucosides of paeony are by the preparation of preparation example 2 methods.
Compositions: take by weighing the salvianolic acid extract, extract of total glucosides of paeony is an amount of, the ratio and the concentration that need in the test requirements document preparation.Chlorination nitro blue tetrazolium (N-BT) is provided by Military Medical Science Institute medical supply station.
Laboratory animal: regular grade SD rat, male, body weight 280g-350g, natural drug Engineering Technical Research Centre zoopery center, Shandong Province provides.The quality certification number: No. 200106005, Shandong kinoplaszm word.
(2) method and result:
Animal is divided into model control group (normal saline) at random, Nifedipine group (6mg/kg), salvianolic acid extract group (3mg/kg), salvianolic acid extract group (6mg/kg), extract of total glucosides of paeony group (3mg/kg), extract of total glucosides of paeony group (6mg/kg), compositions group 1 (salvianolic acid extract (0.6mg/kg)+extract of total glucosides of paeony (5.4mg/kg)), compositions group 2 (salvianolic acid extract (5.4mg/kg)+extract of total glucosides of paeony (0.6mg/kg)), compositions group 3 (salvianolic acid extract (1mg/kg)+extract of total glucosides of paeony (5mg/kg)), compositions thing group 4 (salvianolic acid extract (5mg/kg)+extract of total glucosides of paeony (1mg/kg)), compositions group 5 (salvianolic acid extract (3mg/kg)+extract of total glucosides of paeony (3mg/kg)), compositions group 6 (salvianolic acid extract (2mg/kg)+extract of total glucosides of paeony (4mg/kg)), compositions group 7 (salvianolic acid extract (4mg/kg)+extract of total glucosides of paeony (2mg/kg)), compositions group 8 (salvianolic acid extract (30mg/kg)+extract of total glucosides of paeony (30mg/kg)), compositions group 9 (salvianolic acid extract (15mg/kg)+extract of total glucosides of paeony (15mg/kg) oral dose group), compositions group 10 (salvianolic acid extract (100mg/kg)+extract of total glucosides of paeony (100mg/kg) oral dose group), compositions group 11 (salvianolic acid extract (300mg/kg)+extract of total glucosides of paeony (300mg/kg) oral dose group).Every group 10.After the fasting 12 hours, limbs II lead electrocardiogram is surveyed in ip. urethane (1.2g/kg) anesthesia.Cut off left front fur, iodine tincture and alcohol disinfecting, along left border of sternum 1cm place, cut off thoracic wall muscle and two ribs, open the thoracic cavity rapidly, expose heart, the ligation left coronary artery is put back to heart immediately between arterial cone and left auricle, squeezes the thoracic cavity air, use the mosquito forceps closed-chest, cause Model Rats with Acute Myocardial Ischemia.Nifedipine group is gastric infusion before anesthesia, composition oral dosage group successive administration 3 days, and fasting is after 16 hours after administration in the 2nd day, and administration in the 3rd day was performed the operation after 30 minutes, and all the other respectively organize postoperative with both intravenous injection relative medicines.1.5h, 3h electrocardiogram before the record administration and after the administration measure the lift-off value of electrocardiogram J point, take out heart behind the 6h, with cold saline clean after ,-20 ℃ of refrigerator freeze overnight.Next day, refrigerated heart is cut into 5 by ligation place to apex uniform thickness, immerse in the freshly prepared 0.25%N-BT phosphate buffer (pH 7.4).37 ℃ of water-bath jolting 10～15min.Blot the dyeing liquor of slice surface with filter paper, separate the coloured portions and the part of being unstained, weigh the compute infarct size.Infarct size (%)=infarction part weight/(non-infarction part weight+infarction part weight) * 100%.Data are represented with X ± s, carry out statistical procedures with t check between group.
The result is as shown in table 1, and myocardial ischemia is after 6 hours, and tangible kitchen range shape ischemic region appears in the model group rat heart muscle, reaches about 26%.3mg/kg salvianolic acid extract and 3mg/kg extract of total glucosides of paeony group fail to reduce rising, the minimizing ischemic areas of limb lead electrocardiogram J point; 6mg/kg salvianolic acid extract and 6mg/kg extract of total glucosides of paeony group, compositions group 9 all reduce rising, the minimizing ischemic areas (comparing p＜0.05 with model group) of limb lead electrocardiogram J point to a certain extent; Rising, minimizing ischemic areas that compositions group 1, compositions group 2, compositions group 3, compositions group 4, compositions group 5, compositions group 6, compositions group 7 reduce limb lead electrocardiogram J point significantly (compare with model group, p＜0.01), the rising of compositions group 1, compositions group 2, compositions group 3, compositions group 4, compositions group 5, compositions group 6,7 pairs of limb lead electrocardiogram J points of compositions group, minimizing ischemic areas and 6mg/kg salvianolic acid extract group, 6mg/kg extract of total glucosides of paeony group more also have significant difference (p＜0.05); Compositions group 8, compositions group 10, compositions group 11 reduce rising, the minimizing ischemic areas (comparing p＜0.001 with model group) of limb lead electrocardiogram J point extremely significantly; Compositions group 10 compares with compositions group 11, to the rising and the ischemic areas no significant difference (p＞0.05) of limb lead electrocardiogram J point.
Table 1 salvianolic acid extract, extract product of paeoniflorin, compositions are to the influence of rat heart muscle ischemic injuries
Compare with model control group,
*P＜0.05,
*P＜0.01,
* *P＜0.001.
Compare with dosage group in the salvianolic acid,
#P＜0.05; Compare with dosage group in the extract product of paeoniflorin,
MP＜0.05
Test example 2: the present composition is to the influence of rat local cerebral ischemia damage
(1) material:
Salvianolic acid extract, extract of total glucosides of paeony are by the preparation of preparation example 2 methods.
Compositions: take by weighing the salvianolic acid extract, extract of total glucosides of paeony is an amount of, the ratio and the concentration that need in the test requirements document preparation.
Red tetrazolium: U.S. Sigma company product, face with preceding and be made into 4% solution with normal saline.
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, natural drug Engineering Technical Research Centre zoopery center, Shandong Province provides.The quality certification number: No. 200106005, Shandong kinoplaszm word.
(2) method and result:
Animal is divided into model control group (normal saline) at random, nimodipine group (1.0mg/kg), salvianolic acid extract group (3mg/kg), salvianolic acid extract group (6mg/kg), extract of total glucosides of paeony group (3mg/kg), extract of total glucosides of paeony group (6mg/kg), compositions group 1 (salvianolic acid extract (0.6mg/kg)+extract of total glucosides of paeony (5.4mg/kg) group), compositions group 2 (salvianolic acid extract (5.4mg/kg)+extract of total glucosides of paeony (0.6mg/kg) group), compositions 3 (salvianolic acid extract (1mg/kg)+extract of total glucosides of paeony (5mg/kg) group), compositions group 4 (salvianolic acid extract (5mg/kg)+extract of total glucosides of paeony (1mg/kg) group), compositions group 5 (salvianolic acid extract (3mg/kg)+extract of total glucosides of paeony (3mg/kg) dosage group, compositions 6 (salvianolic acid extract (2mg/kg)+extract of total glucosides of paeony (4mg/kg) group), compositions 7 (salvianolic acid extract (4mg/kg)+extract of total glucosides of paeony (2mg/kg) group, compositions group 8 (salvianolic acid extract (30mg/kg)+extract of total glucosides of paeony (30mg/kg) group), compositions group 9 (salvianolic acid extract (15mg/kg)+extract of total glucosides of paeony (15mg/kg) oral dose group), compositions 10 (salvianolic acid extract (100mg/kg)+extract of total glucosides of paeony (100mg/kg) oral dose group), compositions 11 (salvianolic acid (300mg/kg)+extract product of paeoniflorin (300mg/kg) oral dose group).Every group 10.Every group 10.After the fasting 12 hours, and chloral hydrate (350mg/kg, i.p.) anesthesia separates right carotid, and folder closes in the neck, common carotid artery, external carotid artery proximal part and distal end ligation, cut off the centre.The external carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire for use, length 5.0cm) is inserted into intracranial by external carotid artery, stop when meeting slight resistance, insertion depth is about 2cm.Ligation external carotid artery opening, and open the common carotid artery bulldog clamp, the disinfection and stitching wound causes right side middle cerebral artery ischemia model; Sham operated rats is only carried out the separation (above experiment is all carried out at 23 ℃～25 ℃) of right carotid, internal carotid artery, external carotid artery.Composition oral dosage group successive administration 3 days, fasting is after 16 hours after administration in the 2nd day, and administration in the 3rd day was performed the operation after 30 minutes, and all the other respectively organize postoperative intravenous injection relative medicine.Press document [Liu Xiaoguang, Xu Lina, a kind of rat brain medium-sized artery model that can estimate thrombolytic and anti-thrombolytic after 24 hours, Acta Pharmaceutica Sinica, 1995,30:662] described method and standard is observed and the behavior disorder of record rat: (A) carry the Mus tail and observe forelimb flexing situation, stretch to ground as two forelimb symmetries, count 0 fen, the wrist flexing occurs as operation offside forelimb and count 1 fen, the elbow flexing is counted 2 fens, the shoulder inward turning is counted 3 fens, existing wrist flexing and/or elbow flexing have shoulder inward turning person again, count 4 fens.(B) animal is placed on the plane earth, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, count 0 fen, as resistance descender when the operation offside promotes, according to decline degree difference be divided into gently, in, weigh three degree, count 1,2 and 3 fen respectively.(C) the two forelimbs of animal are put on the wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 fen.Count 1,2 and 3 fen according to operation offside muscular tension decline degree difference equally.(D) animal has ceaselessly to a side person of turn-taking, and counts 1 fen.According to the standard scoring, full marks are 11 minutes, and mark is high more, and expression animal behavior obstacle is serious more.
Put to death rat behind the behavior scoring, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, the brain sheet takes on a red color after normal structure is dyed with red tetrazolium (TTC) dyeing, and blocking tissue is white in color, taking a picture in dyeing back, asks the infarct size ratio with Chinese Aero-Space university pathological image analysis software.Data are represented with X ± s, carry out statistical procedures with t check between group.
The result is as shown in table 2, and ischemia is after 24 hours, and the model group rat shows tangible behavior disorder, and tangible kitchen range shape ischemic region also appears in rat cerebral tissue, reaches full brain about 24%.3mg/kg salvianolic acid extract and 3mg/kg extract of total glucosides of paeony group are failed to improve the rat behavior obstacle, are reduced ischemic areas; 6mg/kg salvianolic acid extract and 6mg/kg extract of total glucosides of paeony group, compositions group 9 oral dose groups are all improved the rat behavior obstacle to a certain extent, are reduced ischemic areas (comparing p＜0.05 with model group); Compositions group 1, compositions group 2, compositions group 3, compositions group 4, compositions group 5, compositions group 6, compositions group 7 are significantly improved the rat behavior obstacle, the minimizing ischemic areas (compares with model group, p＜0.01), compositions group 1, compositions group 2, compositions group 3, compositions group 4, compositions group 5, compositions group 6,7 pairs of compositions groups are improved rat behavior obstacle, minimizing ischemic areas and 6mg/kg salvianolic acid extract group, 6mg/kg extract of total glucosides of paeony group relatively, and significant difference (p＜0.05) is also arranged; Compositions group 8, compositions group 10, compositions group 11 are improved the rat behavior obstacle extremely significantly, are reduced ischemic areas (comparing p＜0.001 with model group); Compositions group 10 compares with compositions group 11, to improving the rat behavior obstacle, reducing ischemic areas no significant difference (p＞0.05).
Table 2 salvianolic acid, extract product of paeoniflorin and compositions thereof are to the influence of rat cerebral ischemia damage
Compare with model control group,
*P＜0.05,
*P＜0.01,
* *P＜0.001.
Compare with dosage group in the salvianolic acid,
#P＜0.05; Compare with dosage group in the extract product of paeoniflorin,
MP＜0.05
Claims (10)
1. one kind is the pharmaceutical composition of active component with salvianolic acid extract and extract of total glucosides of paeony, wherein in the salvianolic acid extract 100%＞in danshensu salvianolic acid content 〉=50%, 100%＞Radix Paeoniae Alba total glycosides content 〉=50% in the extract of total glucosides of paeony, 100%＞paeoniflorin content 〉=40%, the portion rate of salvianolic acid extract and extract of total glucosides of paeony are 1: 9～9: 1.
2. pharmaceutical composition according to claim 1 is characterized by: the portion rate of salvianolic acid extract and extract of total glucosides of paeony is 1: 5～5: 1.
3. pharmaceutical composition according to claim 1 and 2, it is characterized by: in the salvianolic acid extract 100%＞in danshensu salvianolic acid content 〉=80%, 100%＞Radix Paeoniae Alba total glycosides content 〉=80%, 100%＞paeoniflorin content 〉=60% in the extract of total glucosides of paeony.
4. pharmaceutical composition according to claim 1 and 2, the salvianolic acid preparation method of extract is:
With red rooted salvia, water logging bubble post-heating extracts, and filters the back merging filtrate, concentrate back dilute sulfuric acid acid precipitation, centrifugal and precipitation separation, precipitation is regulated pH value with sodium hydroxide solution and is made its dissolving, adsorbs by macroporous adsorptive resins, earlier with the pure water eluting, with the alcoholic solution eluting, collect eluent, concentrating under reduced pressure again, regulate pH value and make with extra care, after the concentrated solution lyophilizing promptly.
5. pharmaceutical composition according to claim 5, the salvianolic acid preparation method of extract is:
With the water logging bubble heating extraction secondary of red rooted salvia with 12 times of amounts, filter back merging filtrate, concentrate back with 10% sulphuric acid acid precipitation, centrifugal and precipitation separation, precipitation is regulated pH value with sodium hydroxide solution and is made its dissolving, pass through the D101 macroporous adsorptive resins at 1: 1 according to amount of resin and medical material amount, earlier with 5 times of volume pure water eluting, again with 10 times of column volume eluting of 30% alcoholic solution, collect eluent, concentrating under reduced pressure removes ethanol, regulates pH value and makes with extra care, and concentrated solution through lyophilizing promptly.
6. pharmaceutical composition according to claim 5, the salvianolic acid preparation method of extract is:
With the water logging bubble heating extraction secondary of red rooted salvia with 12 times of amounts, filter back merging filtrate, concentrate back with 10% sulphuric acid acid precipitation, centrifugal and precipitation separation, precipitation is regulated pH value with sodium hydroxide solution and is made its dissolving, pass through AB-8 macroporous adsorptive resins at 1: 1 according to amount of resin and medical material amount, promptly use 20kg macroporous resin packed column, with 10 times of volume deionized-distilled water eluting, collect eluent, concentrating under reduced pressure is regulated pH value and is made with extra care, and concentrated solution through lyophilizing promptly.
7. pharmaceutical composition according to claim 1 and 2, it contains the active component of 60mg～6000mg.
8. the application of the arbitrary described pharmaceutical composition of claim 1-7 in the medicine of preparation treatment or prevention cardiovascular and cerebrovascular disease.
9. application according to claim 8, the application of pharmaceutical composition in preparation treatment or prevention coronary heart disease or anginal medicine.
10. application according to claim 8, the application of pharmaceutical composition in the medicine of preparation treatment or prevention cardiac-cerebral ischemia.
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| CN1413589A (en) * | 2002-10-29 | 2003-04-30 | 沈阳药科大学 | Composition of paeoniflorin and albiflorin and its preparation method |
| CN1498615A (en) * | 2002-11-12 | 2004-05-26 | 军 张 | Preparation made from effective position of red sage root, and its prepn. method |
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| CN1413589A (en) * | 2002-10-29 | 2003-04-30 | 沈阳药科大学 | Composition of paeoniflorin and albiflorin and its preparation method |
| CN1498615A (en) * | 2002-11-12 | 2004-05-26 | 军 张 | Preparation made from effective position of red sage root, and its prepn. method |
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