CN100389793C - Medicinal composition of radix sal viae miltiorrhizae and radix puerariae for treating cardio-cerebro uascular disease and its preparing method - Google Patents
Medicinal composition of radix sal viae miltiorrhizae and radix puerariae for treating cardio-cerebro uascular disease and its preparing method Download PDFInfo
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Abstract
The present invention relates to a medicine composition of red sage root, kudzuvine root and rhizoma corydalis for curing cardiovascular and cerebrovascular diseases, and a preparation method thereof. Red sage root, kudzuvine root and rhizoma corydalis are mixed and are treated by an extraction purification method according to the recipe ratio, and an extract is prepared, the extract is prepared into preparations, such as freeze-dried powder injections, injections, tablets, capsules, or soft capsules, etc., according to various preparation conventional means, and the freeze-dried powder injections are preferentially chosen. Through the confirmation of pharmacological experiments, the medicine of the present invention performs outstanding cure and prevention functions to cardiovascular and cerebrovascular diseases, the medicine can obviously lower the blood viscosity and the blood fat of a patient, improve hemorheology, and prevent thrombopoiesis, and the medicine has no toxic side effect on the liver and kidney and hematuresis. The medicine composition of the present invention has the advantages of accurate curative effect, safety, reliability, controllable quality, etc.
Description
Technical field:
The present invention relates to a kind of red Ge Yuan pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof
Background technology:
Cardiovascular and cerebrovascular disease is known as the No.1 killer who threatens human health always, show that according to relevant investigation report the people that China dies from cardiovascular and cerebrovascular disease every year has more than 300 ten thousand, account for 50% of the annual total death toll of China, and the ill people who survives 75% disability in various degree, 4% is heavy residual.Drug development at treating cardiac and cerebral vascular diseases is in the ascendant, and China's Chinese medicine culture is of extensive knowledge and profound scholarship, and traditional prescription is the treasure-house of a new drug development especially, and therefrom the newtype drug of exploitation treatment and prevention thrombosis is significant.
Red Ge Yuan prescription is made up of Radix Salviae Miltiorrhizae, Radix Puerariae, Rhizoma Corydalis, wherein Radix Salviae Miltiorrhizae effect activating blood and removing stasis, removing heat from blood, pain relieving, nourishing blood to tranquillize the mind.Essentials of Matea Medica is said: " Radix Salviae Miltiorrhizae, nature and flavor gas is put down and is fallen, bitter in the mouth, GUIXIN warp and envelope.Function, broken stagnated blood, tissue regeneration promoting blood, regulating menstruation arteries and veins, heat clearing away and restlessness relieving, merit four things of holding concurrently.Radix Salviae Miltiorrhizae is reposed, sedate, promoting blood circulation, has god to test in fact." Radix Salviae Miltiorrhizae blood circulation promoting and blood stasis dispelling action range, can control the various diseases of stagnation of blood stasis, so be monarch drug.Rhizoma Corydalis in the side is gone into liver, stomach warp, effect circulation of qi promoting, pain relieving, invigorates blood circulation.Rhizoma Corydalis is invigorated blood circulation a little less than the power, and promoting the circulation of QI to relieve pain power is good, strengthens the effect that Radix Salviae Miltiorrhizae is invigorated blood circulation.The Radix Puerariae essentials of Matea Medica is said: " Radix Puerariae, hot sweet property is flat, and Gui Yangming (stomach) warp is doublely gone into spleen channel.Function lightly floats to rise and sends out, and goes into Yangming Channel ".We's concerted application of drugs is smart to be wanted rationally, so the thoracic obstruction, pained disease are had good treatment and preventive effect.
This Fang Ruo uses inconvenience with the medical material direct drug injection, and utilization ratio of drug is low, and curative effect can not guarantee that quality can not be controlled.Therefore be necessary this medicine to be developed with modern extraction separation method and modern preparation means.
Summary of the invention:
One of purpose of the present invention provides a kind of red Ge Yuan pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, and another object of the present invention provides this preparation of drug combination method.
The red Ge Yuan pharmaceutical composition of treatment cardiovascular and cerebrovascular disease provided by the invention is the Radix Salviae Miltiorrhizae by mass ratio 4-8 part, the Radix Puerariae of 1-5 part, and the extract that the Rhizoma Corydalis of 1-3 part is made and the pharmaceutic adjuvant of corresponding dosage form are formed.Can be injection, injection lyophilized powder, tablet, capsule or soft capsule.
Can be by 6 parts of Radix Salviae Miltiorrhizaes of mass ratio, extract that 3 parts of Radix Puerariaes, 1 part of Rhizoma Corydalis are made and lyophilizing adjuvant be made the red Ge Yuan lyophilized injectable powder of injection.
Red Ge Yuan pharmaceutical composition of the present invention can be realized according to the following steps:
1) gets Radix Salviae Miltiorrhizae in 6: 3: 1 ratio, Radix Puerariae, the Rhizoma Corydalis medical material, with deionized water extraction three times, each 6-12 doubly measures, merge three times extracting liquid filtering, filtrate decompression is concentrated into about relative density 1.15-1.25, add 95% medicinal alcohol and regulate amount of alcohol to 70%-80%, regulate pH value to 7.5-8.5, fully stir cold preservation more than 12 hours, remove precipitation, clear liquid reclaims ethanol to using up and continuing to be concentrated between the relative density 1.10-1.20, adding 5-8 doubly measures deionized water and fully stirs, and cold preservation was used purification with macroreticular resin more than 24 hours, collect eluent, eluent concentrates oven dry De Dange unit extract;
2) get red Ge Yuan extract, make corresponding preparations by various preparation routine techniquess.
The red Ge Yuan lyophilized powder of injection of the present invention pharmaceutical composition is made according to the following steps:
1) gets Radix Salviae Miltiorrhizae in 6: 3: 1 ratio, Radix Puerariae, the Rhizoma Corydalis medical material, with deionized water extraction three times, each 8 times of amounts, merge three times extracting liquid filtering, filtrate decompression is concentrated into relative density 1.22-1.25, add 95% medicinal alcohol and regulate amount of alcohol to 80%, regulate pH value to 8.0-8.5, fully stir cold preservation more than 12 hours, remove precipitation, clear liquid reclaims ethanol to using up and continuing to be concentrated between the relative density 1.15-1.20, add 6 times of amount deionized waters and fully stir, cold preservation was used purification with macroreticular resin more than 24 hours, collect eluent, eluent concentrates oven dry De Dange unit extract;
2) fully be dissolved in red Ge Yuan extract in the water for injection, the cold preservation after-filtration that spends the night, filtrate is with damming the ultrafilter membrane ultrafiltration of molecular weight 5000, ultrafiltrate adds the mannitol of 4%-10%, and 80 ℃ of active carbons that add the 0.05-0.1% of liquor capacity keep 20 minutes after-filtration, cross 0.22 micron microporous filter membrane, packing, jump a queue, lyophilizing, gland promptly get the injection freeze-dried powder preparation.
The macroporous adsorbent resin that uses can be but be not limited to D101, AB-8, ADS-5, ADS-7, ADS-8 or HPD-300.
The preparation method of the red Ge Yuan lyophilized powder of the injection of treatment cardiovascular and cerebrovascular disease provided by the invention is finished according to the following steps:
1) gets Radix Salviae Miltiorrhizae Radix Puerariae Rhizoma Corydalis pulverizing medicinal materials in 6: 3: 1 ratio and become coarse powder, with deionized water extraction three times, each 8 times of amounts, merge three times extracting liquid filtering, filtrate decompression is concentrated into relative density 1.22-1.25, add 95% medicinal alcohol and regulate amount of alcohol to 80%, regulate pH value, fully stir cold preservation more than 12 hours to 8.0-8.5, remove precipitation, clear liquid reclaims ethanol to using up and continuing to be concentrated between the relative density 1.15-1.20, adds 6 times of amount deionized waters and fully stirs, and cold preservation is more than 24 hours, use purification with macroreticular resin, preferred ADS-5, AB-8 or ADS-7 macroporous adsorbent resin are collected eluent, and eluent concentrates oven dry De Dange unit extract;
2) fully be dissolved in red Ge Yuan extract in the water for injection, the cold preservation after-filtration that spends the night, filtrate is with 5000 ultrafilter membrane ultrafiltration, ultrafiltrate adds the mannitol of 4%-10%, and 80 ℃ of active carbons that add the 0.05-0.1% of liquor capacity keep 20 minutes after-filtration, cross 0.22 micron microporous filter membrane, packing, jump a queue, lyophilizing, gland promptly get injection pellet Ge Yuan freeze-dried powder preparation.
Wherein the concentration of mannitol preferred 8%.
The macroporous adsorbent resin that uses is the ADS-8 macroporous adsorbent resin more preferably.
The present invention also provides should the application of pellet Ge Yuan pharmaceutical composition in preparation treatment cardiovascular and cerebrovascular diseases medicament.
The invention provides a kind of red Ge Yuan pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, used macroporous adsorbent resin technology and hyperfiltration technique in the technology, make that the gained quality of the pharmaceutical preparations is controlled, process stabilizing.Pharmacological evaluation proof gained pharmaceutical composition of the present invention is having better curative effect aspect the diseases such as treatment angina pectoris and coronary heart disease, guarantees myocardial oxygen delivery in the time of reaching angina pectoris and coronary heart attack and lowers purposes such as cardiac muscle is aerobic.
Specific embodiment:
Embodiment 1: the preparation of red Ge Yuan extract
Get Radix Salviae Miltiorrhizae 6kg, Radix Puerariae (Radix Puerariae) 3kg, Rhizoma Corydalis 1kg medical material, wherein Radix Salviae Miltiorrhizae cutting (0.5-1.5cm), Radix Puerariae and Rhizoma Corydalis are crossed pulverizer, to extraction pot, add deionized water extraction three times, each 60L merges three times extracting liquid filtering, filtrate decompression is concentrated into relative density 1.22-1.25 (measured value 1.23), add 95% medicinal alcohol and regulate amount of alcohol to 80%, regulate pH value, fully stir back cold preservation more than 24 hours to 8.0-8.5 (measured value pH=8.2), remove precipitation, clear liquid reclaims ethanol to the greatest extent and continue to be concentrated between the relative density 1.15-1.20 (measured value 1.18), adds 6 times and measures deionized waters and fully stir, and moves in the freezer cold preservation 24 hours, solution filters, the AB-8 macroporous adsorbent resin that pretreatment is good on the filtrate, 75% ethanol elution is collected eluent, eluent concentrates oven dry De Dange unit extract, is weighed as 188g; Lot number: 040101
Embodiment 2: the preparation of red Ge Yuan extract
Get Radix Salviae Miltiorrhizae 6kg, Radix Puerariae (Radix Puerariae) 3kg, Rhizoma Corydalis 1kg medical material, wherein Radix Salviae Miltiorrhizae cutting (0.5-1.5cm), Radix Puerariae and Rhizoma Corydalis are crossed pulverizer, to extraction pot, add deionized water extraction three times, each 100L merges three times extracting liquid filtering, filtrate decompression is concentrated into relative density 1.22-1.25 (measured value 1.25), add 95% medicinal alcohol and regulate amount of alcohol to 80%, regulate pH value, fully stir back cold preservation more than 24 hours to 8.0-8.5 (measured value pH=8.4), remove precipitation, clear liquid reclaims ethanol to the greatest extent and continue to be concentrated between the relative density 1.15-1.20 (measured value 1.18), adds 6 times and measures deionized waters and fully stir, and moves in the freezer cold preservation 24 hours, solution filters, the ADS-5 macroporous adsorbent resin that pretreatment is good on the filtrate, 75% ethanol elution is collected eluent, eluent concentrates oven dry De Dange unit extract, is weighed as 192g.Lot number: 040110
Embodiment 3: the preparation of red Ge Yuan extract
Get Radix Salviae Miltiorrhizae 6kg, Radix Puerariae (Radix Puerariae) 3kg, Rhizoma Corydalis 1kg medical material, wherein Radix Salviae Miltiorrhizae cutting (0.5-1.5cm), Radix Puerariae and Rhizoma Corydalis are crossed pulverizer, to extraction pot, add deionized water extraction three times, each 90L merges three times extracting liquid filtering, filtrate decompression is concentrated into relative density 1.22-1.25 (measured value 1.22), add 95% medicinal alcohol and regulate amount of alcohol to 80%, regulate pH value, fully stir back cold preservation 24 hours to 8.0-8.5 (measured value pH=8.0), the centrifugal clear liquid that gets of high speed centrifuge, clear liquid reclaims ethanol to the greatest extent and continue to be concentrated between the relative density 1.15-1.20 (measured value 1.15), adds 6 times and measures deionized waters and fully stir, and moves in the freezer cold preservation 24 hours, solution filters, the ADS-7 macroporous adsorbent resin that pretreatment is good on the filtrate, 80% ethanol elution is collected eluent, eluent concentrates oven dry De Dange unit extract, is weighed as 176g.Lot number: the assay of 040115 salvianolic acid B:
Measure according to high performance liquid chromatography (2000 pharmacopeia appendix VI D).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Acetonitrile-methanol-formic acid-water (10: 30: 1: 59) be mobile phase; The detection wavelength is 286nm.Number of theoretical plate calculates by the salvianolic acid B peak should be not less than 4000.
It is an amount of that the preparation precision of reference substance solution takes by weighing the salvianolic acid B reference substance, accurate claims surely, adds water and make every 1ml and contain 60 μ g, promptly.
Three batches of extracts of this product (040101,040110,040115) powder 0.1g is got in the preparation of need testing solution respectively, and accurate the title decides, put in the tool plug conical flask, precision adds entry 50ml, supersound process (power 300w, frequency 50kHz) 30 minutes, put coldly, filter, get subsequent filtrate, promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
Three batch sample content results are as shown in table 1:
Table 1 three batch sample content of danshinolic acid B
The mensuration of puerarin content:
Measure according to 2000 editions pharmacopeia high performance liquid chromatography (appendix VI D).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; Methanol-water (25: 75) is a mobile phase; The detection wavelength is 250nm.Number of theoretical plate calculates by puerarin peak should be not less than 4000.
The preparation precision of reference substance solution takes by weighing puerarin reference substance 10mg, puts in the 25ml measuring bottle, adds 30% ethanol to scale, shakes up, and precision is measured 2ml, puts in the 10ml measuring bottle, adds 30% ethanol to scale, shakes up, and promptly gets (containing puerarin 80 μ g among every 1ml).
Three batch sample powder 20mg are got in the preparation of need testing solution, and accurate the title decides, and puts in the conical flask, and the accurate 30% ethanol 50ml that adds claims to decide weight, reflux 30 minutes is put coldly, claims to decide weight again, supplies the weight that subtracts mistake with 30% ethanol, shake up, filter, get subsequent filtrate, promptly.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.
The puerarin content measurement result of three batch samples is as shown in table 2:
Table 2: the puerarin content measurement result of three batch samples
Embodiment 4: the preparation of the red Ge Yuan lyophilized powder of injection
Get red Ge Yuan extract (040110) 19.2g to beaker, add 250ml water for injection, stir ultrasonic abundant dissolving, hide the after-filtration that spends the night to refrigerator and cooled, cross 0.45 micron microporous filter membrane fine straining, filtrate is with 5000 ultrafilter membrane ultrafiltration, ultrafiltrate adds the mannitol of 24g, add the injection water and supply volume, add active carbon 0.2g to 300ml, 80 ℃ keep 20 minutes after-filtration, cross 0.22 micron microporous filter membrane, packing, jump a queue, lyophilizing, gland promptly get injection pellet Ge Yuan freeze-dried powder preparation.Lot number: lyophilized powder 040201
Embodiment 5: the preparation of red Ge Yuan injection
Getting red Ge Yuan extract (040110) 19.2g is dissolved in the 8000ml water for injection, cold preservation was filtered in 24 hours, filtrate adds the sodium sulfite of 0.5g, fully dissolving, after adding water for injection and boiling to the 10000ml, the active carbon that adds 5g boils decarburization in 20 minutes, filter, 0.22 be sub-packed in the 100ml bottle after the micron micropore filter filters, sterilized 30 minutes, and made transfusion for 115 ℃.Lot number: transfusion 040210
Embodiment 6: red Ge Yuan preparation of soft capsule
With 040115 red Ge Yuan extract 3.52g, add soybean oil 30g, Cera Flava 0.8g, mixing is made 100 of soft capsules, promptly.
Embodiment 7: the preparation of red Pueraria lobota Yuan capsule
With 040115 red Ge Yuan extract 3.52g, add 10% dextrin, granulate, make 100 of capsules, promptly.
Embodiment 8: the preparation of red Ge Yuan sheet
040115 red Ge Yuan extract 1.76g is added the 8.0g microcrystalline Cellulose, 0.8g crospolyvinylpyrrolidone is pulverized, ethanol is softening, granulate after crossing 60 mesh sieves, 50 ℃ of dryings are crossed 60 mesh sieve granulate, add the 0.6g carboxymethyl starch sodium, 0.15g Aspartane, 1.5g the magnesium stearate uniform mixing is pressed into 50, promptly.
Embodiment 9: red Ge Yuan is to the influence of mice anoxia enduring
The experiment medicine: lyophilized powder 040201 of the present invention, get 5 and 1, add the solution that normal saline 50ml is prepared into two kinds of variable concentrations.
FUFANG DANSHEN DIWAN with before being ground into fine powder, being got the 500mg adding distil water and is mixed with the suspension that concentration is 10mg/ml.
Normal saline
Laboratory animal: 40 of BALB/c mouse, female
Experimental technique: get 40 of BALB/c mouse, be divided into 10 every group of the heavy dose of groups of normal control group, red Ge Yuan, red Ge Yuan small dose group, Composite Salvia Dropping Pill group at random.Each medicine group is pressed the 0.2ml/10g body weight, gives the heavy dose of medicinal liquid of red Ge Yuan, the low dose of medicinal liquid of red Ge Yuan, FUFANG DANSHEN DIWAN medicine liquid irrigation stomach respectively, and the normal control group waits the capacity normal saline to irritate stomach.Behind the administration 30min, every mice difference lumbar injection isoproterenol 0.1ml/10g body weight then, is put into airtight appearance reason bottle, record mouse diing time with mice.The results are shown in Table 3:
The red Ge Yuan of table 3 to the influence of mice anoxia enduring (x ± s, min)
Annotate: with normal group contrast, * P＜0.05, * * P＜0.01
With Radix Salviae Miltiorrhizae drop pill contrast △ P＜0.05
Embodiment 10: red Ge Yuan is to the influence of Acute Myocardial Ischemia in Rats due to the pituitrin
The experiment medicine: lyophilized powder 040201 of the present invention, get 20 and 5, be dissolved in respectively in the 100ml water for injection, prepare two concentration group samples.
FUFANG DANSHEN DIWAN, with before being ground into fine powder, adding distil water is mixed with the suspension that concentration is 60mg/ml.The pituitrin injection, specification 10u/ml
Normal saline
Laboratory animal: 40 of Wistar II level rat, female, body weight 160g-200g.
Experimental technique: select 40 of healthy rats for use, be divided into 4 groups at random, blank group (normal saline), Composite Salvia Dropping Pill group, heavy dose of group of red Ge Yuan and red Ge Yuan small dose group by body weight.Give the heavy dose of medicinal liquid of red Ge Yuan, the low dose of medicinal liquid of red Ge Yuan, FUFANG DANSHEN DIWAN medicine liquid irrigation stomach respectively, the normal control group waits the capacity normal saline to irritate stomach, each treated animal continuous irrigation stomach 5d, and every day 1 time, irritating the stomach volume is 20ml/kg.After last was irritated stomach 1h, lumbar injection 10% chloral hydrate 3ml/kg anaesthetized, and it is fixing to lie on the back, it is subcutaneous that needle electrode is inserted extremity, and regulate electrocardiogram sensitivity to 1mv=15mm, and chart speed is 50mm/s, record II leads electrocardiogram, selects the electrocardiogram intact animal to carry out tongue intravenous injection pituitrin (0.5u/kg) and causes myocardial infarction and ischemia model, and injection speed is 10s, carry out 15s after the injection immediately, 30s, 1min, 2min, 5min
10min duplicate record electrocardiogram (can write down at any time) according to oscillograph finding abnormal conditions.After experiment finishes, measure the relatively variation of administration forward and backward stipulated time S-T section and T wave height, all data all adopt meansigma methods scholar standard deviation (x ± s) expression, between two groups mean relatively relatively with T, mean is relatively used variance analysis between many groups.The results are shown in Table 4,5:
The red Ge Yuan of table 4 to the influence of Acute Myocardial Ischemia in Rats ECG ST section due to the pituitrin (x ± s, mv)
Annotate: compare * * P＜0.01 with the blank group
Compare △ P＞0.05, △ △ P＜0.01 with the Radix Salviae Miltiorrhizae drop pill group
The red Ge Yuan of table 5 to Acute Myocardial Ischemia in Rats ECG T wave influence due to the pituitrin (x ± s, mv)
Annotate: compare * * P＜0.01 with the blank group
Compare △ P＞0.05, △ △ P＜0.05 with Radix Salviae Miltiorrhizae drop pill
Embodiment 11, red Ge Yuan are to the influence of Acute Myocardial Ischemia in Rats due to the ligation coronary artery
The experiment medicine: lyophilized powder 040201 of the present invention, get 20 and 5, be dissolved in respectively in the 100ml water for injection, prepare two concentration group samples.
FUFANG DANSHEN DIWAN, with before being ground into fine powder, adding distil water is mixed with the suspension that concentration is 60mg/ml.The pituitrin injection, specification 10u/ml
Normal saline
Laboratory animal: 50 of Wistar II level rat, male and female half and half, body weight 160g-200g
Experimental technique: get 50 of the healthy Wistar rats of body weight 200g-240g, be divided into 5 groups at random, normal ligation group not, ischemic control group (normal saline), FUFANG DANSHEN DIWAN, the heavy dose of group of red Ge Yuan small dose group and red Ge Yuan by body weight.Give the heavy dose of medicinal liquid of red Ge Yuan, the low dose of medicinal liquid of red Ge Yuan, FUFANG DANSHEN DIWAN medicine liquid irrigation stomach respectively, the normal control group waits the capacity normal saline to irritate stomach, and irritating the stomach volume is 20ml/kg, every day 1 time, 5d continuously.1h after the last administration, lumbar injection 10% chloral hydrate 3ml/kg anaesthetizes, place on the rat operating-table fixedly dorsal position to fix, the longitudinal incision skin of neck, passivity is separated the trachea surrounding tissue, exposes trachea, circulation of qi promoting pipe interpolation pipe, confirm to insert in the trachea, back suture fixedly intubate by the rat mouth.It is subcutaneous that needle electrode is inserted extremity, and regulate electrocardiogram sensitivity to 1mv=15mm, chart speed is 50mm/s, record II leads electrocardiogram, in rat oxter parallel lines, and the about 1.5cm of left side transection skin, separate the flesh layer in the 4th or the 5th intercostal passivity, open the thoracic cavity, be right after animal respirator, auxiliary rats breathing.Cut off pericardium, gently press the right side thorax, extrude heart, after Coronary vein place between right side circular cone and the left auricle is with 50 silk thread ligation left coronary artery, heart is put back to the thoracic cavity, fully discharge air in the thoracic cavity, sew up and close thoracic cavity, respirator assisted respiartion.At once, 1h, 24h, 48h trace one section electrocardiogram respectively after the ligation, and in 24h, 48h irritates stomach and gives saline under the heavy dose of medicinal liquid of red Ge Yuan, the low dose of medicinal liquid of red Ge Yuan, FUFANG DANSHEN DIWAN medicinal liquid and the physiology.Broken end is got blood behind coronary ligation 50h, measures serum CPK, LDH, and after broken end is got blood, take out heart rapidly. use normal saline flushing, remove blood stains, reject non-cardiac muscular tissues such as blood vessel, fat, inhale the branch that anhydrates, claim weight in wet base whole-heartedly with absorbent paper.Along coronary sulcus excision atrium, stay ventricle, weigh, along coronary sulcus from the apex of the heart to heart base portion 4 of parallel myocardium sheets with ventricular muscles crosscut Cheng Houyue 0.1cm, clean with normal saline flushing.Myocardium sheet is placed in 0.1% the N one BT solution, unnecessary dyestuff is removed in water flushing immediately after dyeing 15min. dyeing under 37 ℃ of water bath condition.Infarcted region is not painted. and non-infarcted region is dyed blueness by N one BT solution.Cut off infarcted myocardium, claim weight in wet base, with the infarcted region weight in wet base, the sheet percentage ratio of weight in wet base is whole-heartedly represented myocardial infarct size.The results are shown in Table 6,7,8:
The red Ge Yuan of table 6 to the influence of acute myocardial ischemia ECG ST section due to the ligation rat coronary artery (x ± s, mv)
Annotate: compare * P＜0.05**P＜0.01 with the blank group
Compare △ P＜0.05 with Radix Salviae Miltiorrhizae drop pill
The red Ge Yuan of table 7 is to the influence of acute myocardial ischemia myocardial infarct size due to the ligation rat coronary artery
Annotate: compare * P＜0.05**P＜0.01 with the blank group
Compare △ P＜0.05 with Radix Salviae Miltiorrhizae drop pill
The red Ge Yuan of table 8 to the influence of acute myocardial ischemia CPK due to the ligation rat coronary artery and LDH (x ± s, iv/L)
Annotate: with normal ligation group * P＜0.05**P＜0.01 not
Compare △ P＜0.05 △ △ P＜0.01 with the blank group
Claims (12)
1. a red Ge Yuan pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease is the extract of being made than Chinese crude drug by following quality
Radix Salviae Miltiorrhizae 4-8: Radix Puerariae 1-5: Rhizoma Corydalis 1-3
Form with the pharmaceutic adjuvant of corresponding dosage form.
2. the red Ge Yuan pharmaceutical composition of treatment cardiovascular and cerebrovascular disease as claimed in claim 1 is characterized in that it can being the dosage form of injection, injection lyophilized powder, tablet, capsule or soft capsule.
3. a kind of red Ge Yuan pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease as claimed in claim 1 is characterized in that the extract of being made than Chinese crude drug by following quality
Radix Salviae Miltiorrhizae: Radix Puerariae: Rhizoma Corydalis is 6: 3: 1
Form with the pharmaceutic adjuvant of corresponding dosage form.
4. red Ge Yuan pharmaceutical composition as claimed in claim 3 is characterized in that being the injection freeze-dried powder, the extract of being made than Chinese crude drug by following quality
Radix Salviae Miltiorrhizae: Radix Puerariae: Rhizoma Corydalis is 6: 3: 1
Form with the lyophilizing adjuvant.
5. red Ge Yuan pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, make according to the following steps:
1) by Radix Salviae Miltiorrhizae Radix Puerariae Rhizoma Corydalis mass ratio 4-8: 1-5: the 1-3 material of getting it filled, with deionized water extraction three times, each 6-12 doubly measures, merge three times extracting liquid filtering, filtrate decompression is concentrated into about relative density 1.15-1.25, add 95% medicinal alcohol and regulate amount of alcohol to 70%-80%, regulate pH value to 7.5-8.5, fully stir cold preservation more than 12 hours, remove precipitation, clear liquid reclaims ethanol to using up and continuing to be concentrated between relative density 1.1 0-1.20, adding 5-8 doubly measures deionized water and fully stirs, and cold preservation was used purification with macroreticular resin more than 24 hours, collect eluent, eluent concentrates oven dry De Dange unit extract;
2) get red Ge Yuan extract, make corresponding preparations by various preparation routine techniquess.
6. as the red Ge Yuan pharmaceutical composition of treatment cardiovascular and cerebrovascular disease as described in the claim 5, it is characterized in that making according to the following steps:
1) gets Radix Salviae Miltiorrhizae Radix Puerariae Rhizoma Corydalis medical material in 6: 3: 1 ratio, with deionized water extraction three times, each 8 times of amounts, merge three times extracting liquid filtering, filtrate decompression is concentrated into relative density 1.22-1.25, add 95% medicinal alcohol and regulate amount of alcohol to 80%, regulate pH value to 8.0-8.5, fully stir cold preservation more than 12 hours, remove precipitation, clear liquid reclaims ethanol to using up and continuing to be concentrated between the relative density 1.15-1.20, add 6 times of amount deionized waters and fully stir, cold preservation was used purification with macroreticular resin more than 24 hours, collect eluent, eluent concentrates oven dry De Dange unit extract;
2) fully be dissolved in red Ge Yuan extract in the water for injection, the cold preservation after-filtration that spends the night, filtrate is with damming the ultrafilter membrane ultrafiltration of molecular weight 5000, ultrafiltrate adds the mannitol of 4%-10%, and 80 ℃ of active carbons that add 0.05-0.1% keep 20 minutes after-filtration, cross 0.22 micron microporous filter membrane, packing, jump a queue, lyophilizing, gland promptly get the injection freeze-dried powder preparation.
7. as the red Ge Yuan pharmaceutical composition of treatment cardiovascular and cerebrovascular disease as described in the claim 6, it is characterized in that the macroporous adsorbent resin that uses is meant D101, AB-8, ADS-5, ADS-7, ADS-8 or HPD-300.
8. red Ge Yuan preparation of drug combination method for the treatment of cardiovascular and cerebrovascular disease is characterized in that finishing according to the following steps:
1) gets Radix Salviae Miltiorrhizae Radix Puerariae Rhizoma Corydalis medical material in 6: 3: 1 ratio, with deionized water extraction three times, each 8 times of amounts, merge three times extracting liquid filtering, filtrate decompression is concentrated into relative density 1.22-1.25, add 95% medicinal alcohol and regulate amount of alcohol to 80%, regulate pH value to 8.0-8.5, fully stir cold preservation more than 12 hours, remove precipitation, clear liquid reclaims ethanol to using up and continuing to be concentrated between the relative density 1.15-1.20, add 6 times of amount deionized waters and fully stir, cold preservation was used purification with macroreticular resin more than 24 hours, collect eluent, eluent concentrates oven dry De Dange unit extract;
2) fully be dissolved in red Ge Yuan extract in the water for injection, the cold preservation after-filtration that spends the night, filtrate is with 5000 ultrafilter membrane ultrafiltration, ultrafiltrate adds the mannitol of 4%-10%, 80 ℃ of active carbons that add the 0.05-0.1% of liquor capacity keep 20 minutes after-filtration, cross 0.22 micron microporous filter membrane, packing, jump a queue, lyophilizing, gland promptly.
9. red Ge Yuan preparation of drug combination method as claimed in claim 8 is characterized in that used macroporous adsorbent resin is meant ADS-5, AB-8 or ADS-7 macroporous adsorbent resin.
10. claim 8 or 9 described red Ge Yuan preparation of pharmaceutical compositions methods, the concentration that it is characterized in that mannitol is 8%.
11. red Ge Yuan preparation of drug combination method as claimed in claim 8, what it is characterized in that using is the AB-8 macroporous adsorbent resin.
12. the application of the described red Ge Yuan pharmaceutical composition of claim 4 in preparation treatment cardiovascular and cerebrovascular diseases medicament.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1144123A (en) * | 1996-06-17 | 1997-03-05 | 重庆祥慧医药高新技术研究所 | Prescription of Xinmaitai and its production process |
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2005
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1144123A (en) * | 1996-06-17 | 1997-03-05 | 重庆祥慧医药高新技术研究所 | Prescription of Xinmaitai and its production process |
Non-Patent Citations (4)
| Title |
|---|
| 冠舒片的薄层色谱鉴别. 马秀璟.药学实践杂志，第14卷第3期. 1996 |
| 冠舒片的薄层色谱鉴别. 马秀璟.药学实践杂志，第14卷第3期. 1996 * |
| 高效液相法测定冠舒片中儿茶醛含量. 张岩.时珍国医国药，第10卷第2期. 1999 |
| 高效液相法测定冠舒片中儿茶醛含量. 张岩.时珍国医国药，第10卷第2期. 1999 * |
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Assignee: Dalian Tianyu Haibin Pharmaceutical Co., Ltd. Assignor: Daguang Pharmaceutical Co., Ltd., Guangdong Contract record no.: 2010210000148 Denomination of invention: Medicinal composition of radix sal viae miltiorrhizae and radix puerariae for treating cardio-cerebro uascular disease and its preparing method Granted publication date: 20080528 License type: Exclusive License Open date: 20060809 Record date: 20100926 |
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