CN1939432A - Injection for treating cardiac cerebrovascular disease and its preparation - Google Patents
Injection for treating cardiac cerebrovascular disease and its preparation Download PDFInfo
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Abstract
An injection for treating cardiovascular and cerebrovascular diseases is prepared from astragalus root, Chuan-xiong rhizome and red peony. Its preparing process is also disclosed.
Description
Technical field
The present invention relates to a kind of Chinese medicine injection for the treatment of cardiovascular and cerebrovascular disease, is raw material with the Chinese crude drug Radix Astragali, Rhizoma Chuanxiong, Radix Paeoniae Rubra specifically, and the injection that is prepared from relates to the preparation method of this medicine simultaneously.
Background technology
Cardiovascular and cerebrovascular disease is the first cause of the death of present industrialized country, its sickness rate even more taller than cancer, only at the annual number of patients of the U.S. just up to more than 1,000,000 person-times.Along with the raising day by day of Chinese society progress and living standards of the people, cardiovascular and cerebrovascular disease has become and has threatened one of able-bodied principal disease of China people, therefore, the prevention and the treatment of cardiovascular and cerebrovascular disease is just had extremely important realistic meaning.
Cardiovascular medicament also is the most active in a new drug research field.According to statistics, kind surplus the new drug that enters clinical research every year on average has 20 approximately makes the Drug therapy of cardiovascular and cerebrovascular disease reach higher level.Treatment to primary disease at present mainly relies on Drug therapy, comprises beta receptor blocker, calcium antagonists, angiotensin-convertion enzyme inhibitor, anti-heart failure medicine, antiplatelet drug etc. substantially.These medicines cost an arm and a leg mostly, and have than significant side effects, and the drawback that rebounds after the ubiquity drug withdrawal.
Therefore, can think like this that the sickness rate of present clinical cardiovascular and cerebrovascular disease is very high, but lack the medicine of safe quick-acting, very necessary when actively developing the novel drugs for the treatment of cardiovascular and cerebrovascular disease.
Summary of the invention
The Chinese medicine injection that the purpose of this invention is to provide a kind of effective treatment cardiovascular and cerebrovascular disease, another object of the present invention provide the preparation method of this Chinese medicine injection.
For achieving the above object, we have adopted following technical scheme:
Chinese medicine injection of the present invention is to be made by the raw material of following weight ratio:
Radix Astragali 2-40 weight portion Rhizoma Chuanxiong 2-20 weight portion Radix Paeoniae 2-20 weight portion.
The weight ratio of the raw material of preparation Chinese medicine injection of the present invention can be preferably:
Radix Astragali 4-20 weight portion Rhizoma Chuanxiong 3-10 weight portion Radix Paeoniae 3-10 weight portion.
The weight ratio of the raw material of preparation Chinese medicine injection of the present invention can be preferably:
The Radix Astragali 10 weight portion Rhizoma Chuanxiongs 5 weight portion Radix Paeoniaes 5 weight portions.
Aforesaid injection wherein Radix Paeoniae is preferably Radix Paeoniae Rubra.
The contained astragaloside of injection of the present invention belongs to peoniflorin all hydrolysis can take place under acid alkali condition, it is improper to select as medicinal liquid PH, can produce white point, white piece even flocculent deposit in the medicinal liquid, influence product quality and curative effect, thereby select suitable pH value in production of this preparation and the storage process and keep that PH's is relatively stable, be vital problem, thereby this product P H-number is fixed between 4.0～9.0
Preparation process thereof of the present invention is:
(1) the extraction process for purification of the Radix Astragali is: get alcohol reflux 1-3 time that the Radix Astragali adds 45-80%, add ethanol 5-10 at every turn and doubly measure extraction 1-3 hour, reclaim ethanol, change water liquid over to and put heavy 24-72 hour, filter, go up macroporous resin then, wash with water, with 3-10 times of volume eluting of 20-40% ethanol to clarification, use the ethanol 4-10 times of volume eluting of 50-80% then, collect eluent, be concentrated into every ml and contain medical material 2-15g, Cryoprecipitation is standby.Be preferably and get alcohol reflux 1-3 time that the Radix Astragali adds 45-80%, add ethanol 5-10 at every turn and doubly measure and extracted 1-3 hour, reclaim ethanol, concentrate, transfer pH value, put cold to 7-10, add hydrochloric acid to PH be 1-5, put heavy 24-72 hour, filter, go up macroporous resin then, wash with water, with 3-10 times of volume eluting of 20-40% ethanol to clarification, use the ethanol 4-10 times of volume eluting of 50-80% then, collect eluent, be concentrated into every ml and contain medical material 2-15g, Cryoprecipitation is standby.
(2) the extraction process for purification of Radix Paeoniae Rubra is: get Radix Paeoniae Rubra and add 4-10 times of water gaging extraction 1-3 time, extracted 1-3 hour at every turn, concentrate, add ethanol and reach 50-80%, put heavy 24-48 hour, filter to containing the alcohol amount, go up macroporous resin then, wash with water, with the ammonia eluting of 0.5-5% to clarification, be washed to neutrality, with 3-10 times of volume eluting of 20-40% ethanol, use the ethanol 4-10 times of volume eluting of 50-80% then, collect eluent, be concentrated into every ml and contain medical material 2-15g, Cryoprecipitation is standby.
(3) the extraction process for purification of Rhizoma Chuanxiong is:
Get alcohol reflux 1-3 time that Rhizoma Chuanxiong adds 45-80%, add ethanol 5-10 at every turn and doubly measure and extracted 1-3 hour, reclaim ethanol, concentrate, add ethanol to 70-80%, put heavy 24-48 hour, filter, polyamide column then, wash with water, continue, collect eluent with 3-10 times of volume eluting of 20-40% ethanol, be concentrated into every ml and contain medical material 2-15g, it is standby to add water water precipitating 24-72 hour.
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Rubra Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, embedding sterilization or lyophilization are aseptic subpackaged, check, promptly.
Pharmaceutical composition of the present invention, good effect, toxic and side effects are few.Be the therapeutical effect and the toxic and side effects that show medicine of the present invention, we have done a large amount of experimentatioies, below experimental example be used to further specify the present invention.
Influence to anesthesiaing dog heart blood flowing dynamics and cerebral circulation
Test objective: be subjected to of the influence of reagent thing by observation, verify that itself and clinical function cure mainly relevant effect to anesthesiaing dog heart blood flowing dynamics and cerebral circulation.
1 group and dosage:
(1) normal saline group: 0.9% sodium chloride injection.
(2) positive drug group: nimodipine 0.2mg/kg.
(3), (4), the high, medium and low dosage group of (5) injection of the present invention.
20.2.4.2 experimental implementation:
(1) to the influence of anesthetized dog cerebral circulation
Get healthy hybrid dog, body weight is 8.5～13.0kg, the male and female dual-purpose.Be divided into 5 groups at random, be normal saline matched group, positive drug group, high, medium and low 3 the dosage groups of injection of the present invention, after anaesthetizing with 3% pentobarbital sodium 1ml/kg (30mg/kg) by the latent venule of forelimb, dorsal position is fixed on the operating-table, cut skin after the unhairing of trachea right side, neck center, find out common carotid artery, after wearing preplaced line, separate along the common carotid artery distal end, find out external carotid artery and ligation, select quite to pop one's head in, connect daily output MF-26 type electromagnetic flowmeter to measure the blood flow of internal carotid artery blood vessel with the common carotid artery diameter; Separating right lower extremity limb vein and intubate uses in order to intravenously administrable; Separate the right lower extremity femoral artery, intubate connects direct hydrargyrum manometer, to trace blood pressure.Treat that operation finishes, after animal is stablized 30 minutes, note down ICAF amount and blood pressure respectively,, and after administration, noted down internal carotid artery vascular flow amount and blood pressure in 1,5,10,15,30,45,60,90 and 120 minute respectively then by different group intravenously administrables.After the off-test, take out immediately that cerebral tissue is weighed and divided by 2, to calculate the blood flow and the cerebral vascular resistance of every 100g cerebral tissue of each time period, respectively with the normal saline matched group relatively, carry out statistical procedures.
(2) to the influence of anesthesiaing dog heart blood flowing dynamics
Get healthy hybrid dog, body weight is 8.5～13.0kg, the male and female dual-purpose.Be divided into 5 groups at random, i.e. normal saline matched group, positive drug group, high, medium and low 3 the dosage groups of injection of the present invention after being anaesthetized with 3% pentobarbital sodium 1ml/kg (30mg/kg) by the latent venule of forelimb, are got dorsal position and are fixed.The cervical region median incision exposes and tracheostomize, and the trachea intubate is in order to the artificial respiration; Separate the right side external jugular vein and carry out oxygen content mensuration usefulness in order to the coronary sinus vein intubate; Separate the right lower extremity femoral artery, water receiving silver manometer is directly traced blood pressure; Separate the right lower extremity femoral artery and carry out arterial oxygen content mensuration in order to blood sampling; Separate the left lower extremity femoral vein and connect infusion bottle, use to replenish body fluid and the intravenously administrable lost; The subcutaneous fixedly needle electrode of extremity is traced the electrocardiogram that standard limbs II leads, to calculate heart rate; Animal is got the right clinostatism of forelimb then, the anterior pectorial region unhairing, Yu Zuosi, five intercostals cut skin along the 4th rib lower edge, the passivity separating muscle, after exposing pleura, connect artificial respirator, fully pleura is cut in the hemostasis back, mention pericardium and cut and do the pericardium bed, stay preplaced line behind careful separation LCA and the aortic root,, select and connect suitable electromagnetic flowmeter to pop one's head in according to coronary artery and aortal thickness; (inject anticoagulant heparin in the cardiac catheter) from right jugular vein intubate to coronary sinus vein.After aforesaid operations finished, the intravenous injection heparin carried out whole body heparinization (5mgkg
-1). after treating that animal is stablized 30 minutes, observe and recording blood pressure, electrocardiogram, coronary flow and aorta flow, and get blood from femoral artery and coronary sinus vein and carry out oxygen content and measure, as the normal value before the administration.Then according to behind different groups and the dosage intravenously administrable, after administration, measured coronary artery, ABF, blood pressure and electrocardiogram etc. respectively in 1,5,15,30,45,60,90 and 120 minute, and coronary sinus vein and femoral artery oxygen content are surveyed in 30 minutes and 60 minutes blood sampling after administration.After experiment finishes, take out heart and weigh.According to the result, blood pressure, heart rate, coronary artery blood flow, ABF and oxygen content are carried out statistical procedures, and calculate cardiac output, cardiac index, SI, the work done of left chamber, per minute 100 gram myocardial flow, coronary resistance, total peripheral resistance, myocardial oxygen consumption, myocardium coefficient of oxygen utilization and myocardial oxygen consumption index etc. according to formula.
1. cerebral vascular resistance (mmHg.ml.100g.min
-1)=mean arterial blood pressure/cerebral blood flow
2. cardiac output (ml/beat)=cardiac output/heart rate
3. cardiac index (L/min/m
2)=cardiac output/body surface area
4. SI (L/beat/m
2)=cardiac index/heart rate * 10
3
5. stroke work index (kg.m/min/m
2)=cardiac index * 1.052 * (blood pressure-5) * 13.6 * 10
3
6. per minute hectogram myocardial flow (ml/100g/min)=coronary flow/(1/3 cardiac weight * 100)
7. coronary resistance (mmHg/ml/100g/min)=blood pressure/per minute 100g myocardial flow
8. total peripheral resistance (dyne .s.cm
3)=blood pressure * 79.92/ cardiac output
9. myocardial oxygen consumption=(arterial blood oxygen amount-coronary sinus vein blood oxygen amount) * coronary flow * 10
-2
10. myocardium coefficient of oxygen utilization (%)=(arterial blood oxygen amount-coronary sinus vein blood oxygen amount) * arterial blood oxygen amount * 100
11. myocardial oxygen consumption index=heart rate * blood pressure * 10
-2
3 experimental results:
Influence to anesthetized dog cerebral tissue blood flow:
Behind the injection high dose group intravenously administrable 5min of the present invention, anesthetized dog cerebral tissue blood flow is increased, and continue to 45min always, the anesthetized dog cerebral vascular resistance is reduced, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 1.
Influence to the anesthetized dog cerebral vascular resistance:
Behind the injection high dose group intravenously administrable 5min of the present invention, the anesthetized dog cerebral vascular resistance is reduced, and continue to 120min always, the anesthetized dog cerebral vascular resistance is reduced, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 2.
Influence to anaesthetized dog blood pressure:
Behind each dosage group intravenously administrable of injection of the present invention, anaesthetized dog blood pressure is not had obvious influence, compare no significant difference with the normal saline group.The results are shown in Table 3, table 4.
Influence to the anesthetized dog heart rate:
Behind each dosage group intravenously administrable of injection of the present invention, the anesthetized dog heart rate is not had obvious influence, compare no significant difference with the normal saline group.The results are shown in Table 5.
Influence to the anesthetized dog coronary flow:
Behind the injection high dose group intravenously administrable 5min of the present invention, the anesthetized dog coronary flow is increased, and continue to 30min always, the anesthetized dog coronary flow is increased, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 6.
To the kinemic influence of anesthetized dog:
Behind the injection high dose group intravenously administrable 5min of the present invention, the anesthetized dog cardiac output is increased, and continue to 30min always; Behind the middle dosage group intravenously administrable anesthetized dog cardiac output is increased, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 7.
Influence to the anesthetized dog coronary resistance:
Behind the injection high dose group intravenously administrable 10min of the present invention, the anesthetized dog coronary resistance is reduced, and continue to 30min always, the anesthetized dog coronary resistance is reduced, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 8.
Influence to the anesthetized dog total peripheral resistance:
Behind the injection high dose group intravenously administrable 5min of the present invention, the anesthetized dog total peripheral resistance is reduced, and continue to 30min always, the anesthetized dog total peripheral resistance is reduced, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 9.
Influence to the anesthetized dog cardiac output:
Behind the injection high dose group intravenously administrable 10min of the present invention, the anesthetized dog cardiac output is increased, and continue to 30min always; Behind the middle dosage group intravenously administrable anesthetized dog cardiac output is increased, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 10.
Influence to the anesthetized dog SI:
Behind the injection high dose group intravenously administrable 10min of the present invention, the anesthetized dog SI is increased, and continue to 30min: the anesthetized dog SI is increased, compare with the normal saline group, there were significant differences (P＜0.05) always.The results are shown in Table 11.
Influence to the anesthetized dog cardiac index:
Behind the injection high dose group intravenously administrable 10min of the present invention, the anesthetized dog cardiac index is increased, and continue to 30min always; Behind the middle dosage group intravenously administrable anesthetized dog cardiac index is increased, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 12.
Influence to the anesthetized dog stroke work index:
Behind each dosage group intravenously administrable of injection of the present invention, the anesthetized dog stroke work index is not had obvious influence, compare no significant difference with the normal saline group.The results are shown in Table 13.
Influence to anesthetized dog per minute hectogram myocardial flow:
Behind the injection high dose group intravenously administrable 1min of the present invention, anesthetized dog per minute hectogram myocardial flow is increased, and continue to 45min always; Behind the middle dosage group intravenously administrable anesthetized dog per minute hectogram myocardial flow is increased, compare with the normal saline group, there were significant differences (P＜0.05).The results are shown in Table 14.
Influence to anesthetized dog myocardial oxygen consumption index, myocardial oxygen consumption, myocardium coefficient of oxygen utilization:
Behind each dosage group intravenously administrable of injection of the present invention, anesthetized dog myocardial oxygen consumption index, myocardial oxygen consumption, myocardium coefficient of oxygen utilization are not had obvious influence, compare no significant difference with the normal saline group.The results are shown in Table 15,16.
Table 1: to the influence of anesthetized dog cerebral tissue blood flow (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | ||
| High dose | Middle dosage | Low dosage | |||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 |
| Time | Different time (the ml.100g.min of cerebral tissue blood flow before and after the administration -1) | ||||
| Before the administration | 329.9±30.4 | 341.5±67.9 | 321.2±44.5 | 317.7±72.4 | 299.0±75.7 |
| After the administration (branch) | 1 5 10 15 30 45 60 90 120 | 333.3±34.2 325.2±36.0 331.5±40.3 324.8±31.8 330.4±31.8 331.7±30.1 322.2±31.2 322.2±31.2 319.8±28.3 | 362.4±76.3 404.7±83.7* 421.3±81.9* 422.1±70.5* 408.1±73.4* 372.7±68.9* 366.8±64.8 337.3±68.9 331.4±64.8 | 354.7±59.1 380.5±64.2* 393.4±74.3* 397.5±72.9* 389.6±63.8* 362.5±52.7* 342.6±50.7 340.5±43.5 332.9±34.3 | 333.0±84.6 382.1±87.4* 390.1±93.0* 401.9±92.6* 405.1±85.7* 372.1±83.0 353.5±68.5 322.7±48.8 322.7±48.8 | 308.6±70.8 337.4±74.1 346.6±76.9 340.7±78.9 330.9±87.0 310.9±68.6 293.7±77.8 271.4±65.7 273.7±64.3 |
Compare with the normal saline group:
*P＜0.05.
Table 2: to the influence of anesthetized dog cerebral vascular resistance (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time cerebral vascular resistance (mmHg.ml.100g.min before and after the administration -1) | |||||
| Before the administration | 0.500±0.219 | 0.429±0.110 | 0.433±0.197 | 0.568±0.332 | 0.462±0.080 | |
| After the administration (branch) | 1 5 10 15 | 0.494±0.222 0.510±0.229 0.505±0.237 0.508±0.250 | 0.357±0.101 0.294±0.077* 0.270±0.068* 0.268±0.059* | 0.368±0.160 0.334±0.144* 0.322±0.141* 0.317±0.131* | 0.539±0.311 0.455±0.262 0.443±0.259 0.423±0.268* | 0.441±0.068 0.403±0.063 0.391±0.061 0.396±0.064 |
| 30 45 60 90 120 | 0.477±0.215 0.475±0.204 0.493±0.211 0.498±0.219 0.505±0.237 | 0.286±0.067* 0.318±0.088* 0.332±0.092* 0.383±0.111* 0.401±0.120* | 0.331±0.144* 0.349±0.155* 0.367±0.165* 0.365±0.149* 0.376±0.150* | 0.401±0.228* 0.444±0.249 0.475±0.269 0.501±0.258 0.497±0.259 | 0.396±0.077 0.425±0.070 0.452±0.089 0.486±0.111 0.483±0.110 |
Compare with the normal saline group:
*P＜0.05.
Table 3: to the influence of anaesthetized dog blood pressure (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time blood pressure (mmHg) before and after the administration | |||||
| Before the administration | 143.0±18.1 | 140.3±4.3 | 143.7±4.5 | 136.0±9.9 | 133.3±13.8 | |
| After the administration (branch) | 1 5 10 15 30 45 60 90 | 141.7±19.1 141.7±18.5 142.5±18.0 139.8±18.3 136.7±16.4 137.0±16.0 137.3±16.4 138.3±17.2 | 123.0±10.4 114.2±15.6* 109.8±16.4* 110.3±15.8* 113.2±15.2* 113.7±18.6* 117.0±17.7* 123.0±12.7 | 137.2±4.8 133.8±6.2 132.0±5.4 132.3±3.7 132.5±3.8 130.0±5.1 130.0±5.1 128.8±4.4 | 135.3±10.9 136.8±12.1 134.8±11.9 130.3±13.4 129.0±12.2 129.2±12.5 132.5±9.6 131.3±8.6 | 132.3±13.1 132.2±12.2 132.0±12.3 130.8±12.5 126.3±18.5 128.7±14.8 127.7±14.6 126.7±12.8 |
| 120 | 138.7±17.6 | 126.7±13.3 | 128.8±5.9 | 130.0±9.1 | 127.0±12.6 |
Compare with the normal saline group:
*P＜0.05.
Table 4: to the influence of anaesthetized dog blood pressure (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time blood pressure (mmHg) before and after the administration | |||||
| Before the administration | 112.3±22.5 | 100.7±22.0 | 114.3±18.3 | 107.7±13.2 | 108.7±9.9 | |
| After the administration (branch) | 1 5 10 15 30 45 60 90 120 | 112.0±22.4 111.3±21.3 112.7±20.3 112.2±21.4 111.0±21.6 110.7±22.2 110.0±24.1 109.7±24.8 111.0±24.6 | 75.7±21.0* 76.7±21.8* 72.3±32.1* 77.7±20.8* 80.7±25.1* 83.0±21.5 85.0±20.7 99.3±17.1 97.7±16.9 | 105.3±14.6 108.3±15.6 107.7±14.3 109.0±12.2 105.3±11.9 101.0±8.6 99.7±9.7 99.0±7.2 104.3±11.3 | 99.2±18.9 103.6±16.5 104.4±15.7 104.4±15.5 95.6±20.4 88.4±23.3 92.8±20.4 96.0±15.9 95.6±20.3 | 109.2±9.1 109.7±9.9 107.8±8.6 107.0±10.6 106.5±11.3 108.3±10.1 109.5±9.3 109.2±8.7 108.8±8.3 |
Compare with the normal saline group:
*P＜0.05.
Table 5: to the influence of anesthetized dog heart rate (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention |
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time heart rate (beat/min) before and after the administration | |||||
| Before the administration | 146.5±25.2 | 159.7±23.5 | 166.0±5.9 | 157.0±9.8 | 158.3±21.2 | |
| After the administration (branch) | 1 5 10 15 30 45 60 90 120 | 145.2±24.6 146.0±26.0 147.0±25.7 145.2±24.6 142.8±24.8 141.3±22.5 141.3±22.5 141.3±22.5 141.3±22.5 | 147.7±32.5 153.5±31.2 155.0±31.7 153.5±30.7 160.7±27.1 159.2±26.4 162.5±18.6 153.7±21.4 153.7±21.4 | 162.5±8.8 162.5±8.8 161.2±9.1 162.3±11.1 159.5±10.4 161.5±14.5 159.7±18.8 162.0±17.1 161.0±17.7 | 152.8±16.6 151.6±16.0 151.8±17.2 149.8±17.8 153.4±17.4 148.2±21.5 143.2±18.8 141.6±18.4 136.2±18.5 | 156.8±22.9 160.7±22.9 158.3±24.0 160.8±23.2 155.0±21.4 156.3±25.9 154.0±26.1 155.0±24.4 152.7±26.2 |
Table 6: to the influence of anesthetized dog coronary flow (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | ||
| High dose | Middle dosage | Low dosage | |||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 |
| Time | Different time coronary flow (ml/min) before and after the administration | ||||
| Before the administration | 22.82±14.52 | 34.12±16.64 | 39.17±13.12 | 27.28±19.59 | 34.78±17.40 |
| After the administration (branch) | 1 5 10 15 30 45 60 90 120 | 23.44±14.34 24.58±16.95 24.43±17.01 25.04±18.66 24.93±17.42 22.98±14.31 22.82±14.52 18.98±9.18 18.36±8.08 | 42.07±14.43 47.69±18.98* 48.94±17.70* 47.08±15.99* 45.83±16.95 43.09±18.51 40.93±17.95 33.64±18.90 33.02±19.25 | 53.85±15.85 56.97±18.09* 59.01±17.44* 58.95±16.13* 56.15±15.63* 53.88±14.58 50.80±14.21 45.24±15.67 42.65±3.35 | 27.74±19.19 30.57±20.75 32.60±18.04 34.16±14.49* 31.62±14.02 29.59±12.63 28.98±13.11 22.78±13.57 22.63±13.65 | 34.43±16.90 37.03±16.00 40.11±18.04 40.46±18.48 39.17±19.03 37.28±17.26 35.38±16.02 29.83±12.99 29.52±13.07 |
Compare with the normal saline group:
*P＜0.05.
Table 7: to the kinemic influence of anesthetized dog (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time cardiac output (L/min) before and after the administration | |||||
| Before the administration | 2.54±1.72 | 3.80±2.48 | 2.58±1.34 | 2.60±1.69 | 2.12±1.46 | |
| After the administration (branch) | 1 5 10 15 | 2.59±1.77 2.58±1.76 2.60±1.77 2.61±1.72 | 4.16±2.61 4.39±2.82* 4.53±2.74* 4.53±2.72* | 2.93±1.54 3.40±1.79* 3.66±1.90* 3.68±1.79* | 3.36±1.45 3.73±1.66* 3.91±1.56* 3.95±1.54* | 2.14±1.44 2.47±1.43 2.56±1.53 2.58±1.57 |
| 30 45 60 90 120 | 2.61±1.80 2.60±1.84 2.56±1.80 2.53±1.78 2.52±1.79 | 4.49±2.74* 4.29±2.83 4.09±2.62 3.83±2.47 3.80±2.48 | 3.43±1.82* 3.07±1.84 2.99±1.80 2.85±1.69 2.78±1.69 | 3.78±1.63* 3.51±1.46* 3.36±1.38 3.32±1.41 3.21±1.47 | 2.48±1.49 2.35±1.40 2.32±1.35 2.32±1.35 2.30±1.36 |
Compare with the normal saline group:
*P＜0.05.
Table 8: to the influence of anesthetized dog coronary resistance (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time coronary resistance (mmHg/ml/100g/min) before and after the administration | |||||
| Before the administration | 1.06±0.33 | 0.85±0.28 | 0.67±0.35 | 0.88±0.30 | 0.80±0.26 | |
| After the administration (branch) | 1 5 10 15 30 45 60 90 | 1.01±0.34 1.08±0.31 1.02±0.30 1.04±0.37 1.02±0.31 1.09±0.34 1.07±0.32 1.05±0.35 | 0.43±0.13* 0.39±0.13* 0.34±0.18* 0.40±0.14* 0.43±0.19* 0.49±0.22 0.54±0.25 0.69±0.31 | 0.59±0.23 0.56±0.28 0.52±0.22* 0.53±0.26* 0.52±0.22* 0.55±0.27 0.59±0.22 0.60±0.37 | 0.81±0.34 0.51±0.30* 0.46±0.21* 0.56±0.27* 0.70±0.35 0.66±0.32 0.78±0.26 0.63±0.20 | 0.81±0.37 0.71±0.29 0.65±0.26 0.64±0.24 0.67±0.27 0.70±0.27 0.76±0.32 0.84±0.31 |
| 120 | 1.10±0.31 | 0.72±0.30 | 0.61±0.31 | 0.70±0.19 | 0.85±0.31 |
Compare with the normal saline group:
*P＜0.05.
Table 9: to the influence of anesthetized dog total peripheral resistance (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time total peripheral resistance (dyne .s.cm before and after the administration 3) | |||||
| Before the administration | 4366.6±2242.2 | 2912.2±1306.2 | 3877.7±1613.3 | 3300.2±1826.5 | 4567.9±1841.7 | |
| After the administration (branch) | 1 5 1 0 1 5 3 0 4 5 6 0 9 0 1 2 0 | 4280.4±2175.9 4275.0±2155.6 4305.5±2152.5 4097.5±2828.3 4245.3±2160.9 4323.7±2206.0 4422.2±2377.5 4297.6±2071.4 4441.5±2250.3 | 1995.0±959.8* 1937.2±941.7* 1691.2±917.8* 1730.4±970.2* 1801.2±900.6* 2026.3±954.3 2197.1±993.1 2396.8±968.7 2472.4±1170.3 | 3198.2±1338.4 2899.6±1263.1* 2598.4±903.2* 2567.5±977.0* 2772.5±962.5* 3181.3±911.9 3256.1±938.3 3050.3±1180.2 3248.2±1497.6 | 2282.1±1191.7 2137.7±1166.4 2022.1±945.6* 1999.8±934.7* 1971.2±964.4* 1951.8±907.7* 1810.4±967.6* 1767.6±892.4* 1829.2±998.8* | 4573.1±1824.4 4362.1±1762.9 4159.1±1679.6 4085.7±1289.9 4236.5±1268.8 4535.8±1503.4 4645.9±1489.9 4648.1±1619.7 4721.6±1487.9 |
Compare with the normal saline group:
*P＜0.05.
Table 10: to the influence of anesthetized dog cardiac output (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time cardiac output (ml/beat) before and after the administration | |||||
| Before the administration | 18.96±14.98 | 23.28±19.25 | 15.60±8.06 | 17.83±10.14 | 14.54±7.38 | |
| After the administration (branch) | 1 5 10 15 30 45 60 90 120 | 19.50±15.36 19.27±15.28 19.33±15.35 19.64±15.06 19.99±15.59 19.96±15.87 19.70±15.57 19.40±15.31 19.33±15.39 | 28.41±12.49 28.63±12.48 29.40±12.04* 29.57±11.87* 28.04±12.08 26.98±12.58 25.56±13.05 25.42±13.24 25.20±13.34 | 18.22±9.84 21.12±11.35 23.01±12.15* 23.04±11.71* 21.98±12.47 19.63±12.63 18.93±11.42 18.09±11.52 17.80±11.56 | 22.34±10.37 25.54±12.15* 26.50±11.48* 27.05±11.39* 25.16±11.81* 24.19±11.49* 24.22±10.79* 23.19±10.31 23.50±11.29 | 14.66±7.32 15.24±7.79 15.96±8.23 15.83±8.51 15.72±7.97 14.80±7.34 14.73±6.94 14.63±6.98 14.44±6.25 |
Compare with the normal saline group:
*P＜0.05.
Table 11: to the influence of anesthetized dog SI (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | ||
| High dose | Middle dosage | Low dosage | |||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 |
| Time | Different time SI (L/beat/m before and after the administration 2) | ||||
| Before the administration | 36.81±11.26 | 45.44±16.80 | 31.04±11.47 | 33.02±19.16 | 28.67±15.67 | |
| After the administration (branch) | 1 5 10 15 30 45 60 90 120 | 37.88±12.06 37.46±12.00 37.51±12.04 38.04±11.57 38.76±12.44 38.68±13.01 37.42±12.49 37.70±12.01 36.86±12.39 | 55.03±12.79 55.58±12.93 57.13±12.21* 57.58±11.94* 54.49±12.00 52.43±12.93 49.68±13.70 49.49±14.15 49.11±14.36 | 36.43±16.25 42.35±19.83 46.23±12.16* 46.12±10.85* 44.28±12.67 39.84±12.39 38.19±19.40 36.65±19.67 36.07±19.68 | 40.30±10.14 46.08±13.37 47.70±12.07* 48.72±11.91* 45.49±12.97 43.79±12.39 43.81±10.93 41.97±10.42 42.68±12.21 | 28.90±15.53 30.09±16.57 31.49±17.48 31.26±18.13 30.99±16.93 29.16±15.66 29.02±14.80 28.84±14.90 28.53±13.41 |
Compare with the normal saline group:
*P＜0.05.
Table 12: to the influence of anesthetized dog cardiac index (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time cardiac index (L/min/m before and after the administration 2) | |||||
| Before the administration | 4.95±2.68 | 7.43±3.63 | 5.14±2.58 | 4.75±3.23 | 4.59±2.73 | |
| Administration | 1 5 | 5.06±2.79 5.03±2.79 | 8.08±3.83 8.51±3.24 | 5.86±2.12 6.81±2.72 | 6.05±2.88 6.83±3.27 | 4.59±2.73 4.92±3.08 |
| Back (branch) | 10 15 30 45 60 90 120 | 5.06±2.78 5.08±2.71 5.10±2.85 5.07±2.93 5.00±2.84 4.95±2.82 4.94±2.85 | 8.79±3.09 8.80±3.06 8.71±3.08 8.33±3.25 7.95±3.87 7.47±3.58 7.41±3.62 | 7.35±2.01* 7.34±2.76* 6.88±2.81 6.20±2.76 6.02±2.62 5.74±2.37 5.59±2.35 | 7.10±3.09* 7.15±3.06* 6.82±3.23 6.28±2.91 6.12±2.76 5.87±2.82 5.71±2.94 | 5.09±3.28 5.13±3.38 4.93±3.19 4.67±2.99 4.61±2.89 4.61±2.89 4.57±2.91 |
Compare with the normal saline group:
*P＜0.05.
Table 13: to the influence of anesthetized dog stroke work index (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time stroke work index (kg.m/min/m before and after the administration 2) | |||||
| Before the administration | 7.78±3.27 | 9.57±4.88 | 7.82±3.82 | 7.22±3.04 | 6.70±3.65 | |
| After the administration (branch) | 1 5 10 15 30 45 | 7.96±3.46 7.86±3.34 7.97±3.30 7.94±3.07 7.87±3.16 7.86±3.36 | 7.86±3.47 8.61±3.84 8.65±3.86 8.20±3.36 9.79±4.92 9.55±4.71 | 8.06±3.86 9.76±3.16 10.67±4.81 10.89±4.84 9.62±4.13 8.28±3.86 | 7.74±2.44 9.14±2.84 9.63±2.54 9.72±2.53 8.40±2.67 7.26±2.88 | 6.79±3.88 7.28±3.33 7.48±3.72 7.50±3.90 7.12±3.39 6.90±3.29 |
| 60 90 120 | 7.50±3.80 7.53±3.77 7.73±3.43 | 9.21±4.90 8.86±4.47 9.08±4.69 | 7.91±3.57 6.89±3.67 6.58±3.20 | 6.50±2.66 5.88±2.64 5.72±2.90 | 6.86±3.11 6.81±4.00 6.73±4.04 |
Compare with the normal saline group:
*P＜0.05.
Table 14: to the influence of anesthetized dog per minute hectogram myocardial flow (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time per minute hectogram myocardial flow (ml/100g/min) before and after the administration | |||||
| Before the administration | 132.3±44.2 | 157.2±55.1 | 195.1±60.7 | 141.8±47.8 | 172.8±51.5 | |
| After the administration (branch) | 1 5 10 15 30 45 60 90 120 | 135.1±43.4 140.7±47.1 149.9±47.3 142.4±45.8 152.3±48.7 142.9±43.4 142.3±44.2 138.1±42.3 138.5±38.4 | 192.8±56.8 217.4±61.2* 222.4±75.7* 212.2±62.0* 207.4±65.7 195.3±63.0 186.5±53.4 149.8±55.8 147.4±47.8 | 257.8±46.6* 274.1±60.1* 282.7±55.9* 281.9±51.4* 268.3±44.2* 258.6±43.4* 242.1±33.9 208.8±24.6 196.4±41.1 | 143.9±47.1 158.7±47.2 169.4±47.5 178.3±42.8* 166.4±42.1 155.7±51.4 152.9±53.4 149.7±51.7 149.2±52.0 | 171.6±51.1 184.2±54.2 201.9±67.6 203.1±67.8 197.4±61.6 187.1±68.6 176.8±57.7 142.5±44.9 141.1±45.7 |
Compare with the normal saline group:
*P＜0.05.
Table 15: to the exponential influence of anesthetized dog myocardial oxygen consumption (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | |||
| High dose | Middle dosage | Low dosage | ||||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 | |
| Time | Different time myocardial oxygen consumption index before and after the administration | |||||
| Before the administration | 163.3±30.1 | 161.3±43.3 | 189.7±30.4 | 169.7±28.7 | 171.4±23.0 | |
| After the administration (branch) | 1 5 10 15 30 45 60 90 120 | 161.5±29.9 161.3±28.7 164.7±30.0 162.0±29.9 157.7±29.6 155.7±29.8 154.5±30.4 153.9±30.9 155.5±29.5 | 116.3±55.4* 121.3±53.4* 114.4±63.4* 121.7±48.1* 132.2±51.5 134.8±47.9 139.9±43.8 134.3±40.2 137.6±39.7 | 171.5±28.5 176.5±30.7 173.5±24.8 176.5±19.3 168.3±24.6 163.3±21.8 158.7±20.9 148.9±17.7 148.4±21.5 | 153.3±42.7 158.5±38.8 159.7±27.5 157.6±37.6 147.8±41.8 132.2±46.6 117.4±42.9 108.8±34.9 104.7±41.4 | 170.6±24.3 175.3±22.2 170.5±27.5 171.2±23.1 164.3±22.3 168.8±27.6 168.3±29.3 169.0±28.1 166.4±31.9 |
Compare with the normal saline group:
*P＜0.05.
Table 16: to the influence of anesthetized dog myocardial oxygen consumption, myocardium coefficient of oxygen utilization (X ± S, n=6)
| Group | Normal saline | Nimodipine | Injection of the present invention | ||
| High dose | Middle dosage | Low dosage | |||
| Dosage (mg/kg) | -- | 0.2 | 800 | 400 | 200 |
| Time | Different time myocardial oxygen consumption (ml/100g/min) before and after the administration | ||||
| Before the administration | 5.21±5.79 | 8.00±8.34 | 11.28±4.92 | 8.36±4.97 | 7.34±5.03 | |
| After the administration (branch) | 30 60 | 7.81±8.21 7.27±7.22 | 7.68±4.94 7.17±6.89 | 11.49±5.69 11.43±4.74 | 8.34±2.75 8.75±1.78 | 9.17±6.19 8.69±5.11 |
| Time | Different time cardiac muscle coefficient of oxygen utilization (%) before and after the administration | |||||
| Before the administration | 23.77±16.14 | 24.51±14.91 | 28.30±7.03 | 22.03±8.42 | 25.64±8.56 | |
| After the administration (branch) | 30 60 | 25.20±21.12 27.04±22.36 | 28.61±4.46 33.04±2.01 | 31.69±8.16 37.66±4.27 | 20.11±7.73 23.45±5.75 | 29.42±10.38 33.62±12.26 |
Compare no significant difference with the normal saline group.
Embodiment 1
Radix Astragali 2kg Rhizoma Chuanxiong 20kg Radix Paeoniae Rubra 20kg
(1) gets the Radix Astragali and add 80% alcohol reflux 3 times, add 8 times of amounts of ethanol at every turn and extracted 2 hours, reclaim ethanol, concentrate, transfer pH value to 8, put cold, add hydrochloric acid to PH be 3, put heavy 48 hours, filter, go up then macroporous resin D101,, wash with water to clarification, with 6 times of volume eluting of 40% ethanol, use 8 times of volume eluting of ethanol of 70% then, collect eluent, be concentrated into every ml and contain medical material 10g, Cryoprecipitation is standby;
(2) get Radix Paeoniae Rubra and add 8 times of water gagings extractions 2 times, extracted 2 hours at every turn, concentrate, add ethanol and reach 70%, put heavy 24 hours, filter to containing the alcohol amount, go up macroporous resin HPD100 then, wash with water, ammonia eluting with 1% to clarification, be washed to neutrality, with 4 times of volume eluting of 30% ethanol, use 8 times of volume eluting of ethanol of 50% then, collect eluent, be concentrated into every ml and contain medical material 10g, Cryoprecipitation is standby;
(3) get Rhizoma Chuanxiong and add 70% alcohol reflux 2 times, add 8 times of amounts of ethanol at every turn and extracted 2 hours, reclaim ethanol, concentrate, add ethanol to 80%, put heavy 24 hours, filter, polyamide column then, wash with water, continue, collect eluent with 8 times of volume eluting of 40% ethanol, be concentrated into every ml and contain medical material 10g, it is standby to add water water precipitating 48 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Rubra Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, the embedding sterilization, check, promptly.
Embodiment 2
Radix Astragali 400g Rhizoma Chuanxiong 20g Radix Paeoniae 200g
(1) gets the Radix Astragali and add 45% alcohol reflux 3 times, add 5 times of amounts of ethanol at every turn and extracted 1 hour, reclaim ethanol, concentrate, transfer pH value to 10, put cold, add hydrochloric acid to PH be 5, put heavy 72 hours, filter, go up low pole macroporous resin AB-8 then, wash with water, with 3 times of volume eluting of 40% ethanol to clarification, use 4 times of volume eluting of ethanol of 50% then, collect eluent, be concentrated into every ml and contain medical material 2g, Cryoprecipitation is standby;
(2) get Radix Paeoniae and add 10 times of water gagings extractions 1 time, extracted 3 hours, concentrate, add ethanol and reach 50%, put heavy 24 hours, filter to containing the alcohol amount, go up macroporous resin D101 then, wash with water, ammonia eluting with 0.5% to clarification, be washed to neutrality, with 3 times of volume eluting of 20% ethanol, use 4 times of volume eluting of ethanol of 50% then, collect eluent, be concentrated into every ml and contain medical material 2g, Cryoprecipitation is standby;
(3) get Rhizoma Chuanxiong and add 45% alcohol reflux 3 times, add 5 times of amounts of ethanol at every turn and extracted 1 hour, reclaim ethanol, concentrate, add ethanol to 70%, put heavy 24 hours, filter, polyamide column then, wash with water, continue, collect eluent with 3 times of volume eluting of 20% ethanol, be concentrated into every ml and contain medical material 2g, it is standby to add water water precipitating 24 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, lyophilization is aseptic subpackaged, check, promptly.
Embodiment 3
Radix Astragali 400g Rhizoma Chuanxiong 200g Radix Paeoniae 20g
(1) gets the Radix Astragali and add 80% alcohol reflux 1 time, add 10 times of amounts of ethanol and extracted 3 hours, reclaim ethanol, concentrate, transfer pH value to 7, put cold, add hydrochloric acid to PH be 1, put heavy 24 hours, filter, macroporous resin HPD450 washes with water to clarification then, with 10 times of volume eluting of 20% ethanol, use 10 times of volume eluting of ethanol of 80% then, collect eluent, be concentrated into every ml and contain medical material 15g, Cryoprecipitation is standby;
(2) get Radix Paeoniae and add 4 times of water gagings extractions 3 times, extracted 1 hour at every turn, concentrate, add ethanol and reach 80%, put heavy 24 hours, filter to containing the alcohol amount, go up macroporous resin AB-8 then, wash with water, ammonia eluting with 5% to clarification, be washed to neutrality, with 0 times of volume eluting of 40% ethanol, use 10 times of volume eluting of ethanol of 80% then, collect eluent, be concentrated into every ml and contain medical material 15g, Cryoprecipitation is standby
(3) get Rhizoma Chuanxiong and add 80% alcohol reflux 1 time, add 10 times of amounts of ethanol and extracted 3 hours, reclaim ethanol, concentrate, add ethanol to 80%, put heavy 48 hours, filter, polyamide column then, wash with water, continue, collect eluent with 10 times of volume eluting of 40% ethanol, be concentrated into every ml and contain medical material 15g, it is standby to add water water precipitating 72 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, the fill lyophilization, check, promptly.
Embodiment 4
Radix Astragali 40g Rhizoma Chuanxiong 100g Radix Paeoniae 100g
(1) gets the Radix Astragali and add 70% alcohol reflux 2 times, add 8 times of amounts of ethanol at every turn and extracted 2.5 hours, reclaim ethanol, concentrate, transfer pH value to 8, put cold, add hydrochloric acid to PH be 2, put heavy 48 hours, filter, go up then low pole macroporous resin D101,, wash with water to clarification, with 5 times of volume eluting of 40% ethanol, use 6 times of volume eluting of ethanol of 60% then, collect eluent, be concentrated into every ml and contain medical material 5g, Cryoprecipitation is standby;
(2) get Radix Paeoniae and add 8 times of water gagings extractions 2 times, extracted 2.5 hours at every turn, concentrate, add ethanol and reach 60%, put heavy 48 hours, filter to containing the alcohol amount, go up macroporous resin HPD100 then, wash with water, ammonia eluting with 1% to clarification, be washed to neutrality, with 8 times of volume eluting of 30% ethanol, use 8 times of volume eluting of ethanol of 60% then, collect eluent, be concentrated into every ml and contain medical material 5g, Cryoprecipitation is standby;
(3) get Rhizoma Chuanxiong and add 70% alcohol reflux 2 times, add 6 times of amounts of ethanol at every turn and extracted 2.5 hours, reclaim ethanol, concentrate, add ethanol to 75%, put heavy 36 hours, filter, polyamide column then, wash with water, continue, collect eluent with 5 times of volume eluting of 30% ethanol, be concentrated into every ml and contain medical material 5g, it is standby to add water water precipitating 48 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, fill, sterilization, check promptly gets and infuses.
Embodiment 5
Radix Astragali 200g Rhizoma Chuanxiong 30g Radix Paeoniae 100g
(1) gets the Radix Astragali and add 60% alcohol reflux 2 times, add 6 times of amounts of ethanol at every turn and extracted 1.5 hours, reclaim ethanol, change water liquid over to and put heavy 24 hours, filter, go up low pole macroporous resin D101 then, wash with water, with 3 times of volume eluting of 40% ethanol to clarification, use 4 times of volume eluting of ethanol of 80% then, collect eluent, be concentrated into every ml and contain medical material 10g, Cryoprecipitation is standby;
(2) get Radix Paeoniae and add 8 times of water gagings extractions 2 times, extracted 1.5 hours at every turn, concentrate, add ethanol and reach 60%, put heavy 24 hours, filter to containing the alcohol amount, go up macroporous resin HPD100 then, wash with water, ammonia eluting with 1% to clarification, be washed to neutrality, with 3 times of volume eluting of 40% ethanol, use 10 times of volume eluting of ethanol of 50% then, collect eluent, be concentrated into every ml and contain medical material 10g, Cryoprecipitation is standby;
(3) get Rhizoma Chuanxiong and add 60% alcohol reflux 2 times, add 6 times of amounts of ethanol at every turn and extracted 1.5 hours, reclaim ethanol, concentrate, add ethanol to 75%, put heavy 24 hours, filter, polyamide column then, wash with water, continue, collect eluent with 8 times of volume eluting of 20% ethanol, be concentrated into every ml and contain medical material 10g, it is standby to add water water precipitating 24 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, embedding, check, promptly.
Embodiment 6
Radix Astragali 200g Rhizoma Chuanxiong 100g Radix Paeoniae 30g
(1) gets the Radix Astragali and add 65% alcohol reflux 2 times, add 6 times of amounts of ethanol at every turn and extracted 2 hours, reclaim ethanol, change water liquid over to and put heavy 48 hours, filter, go up low pole macroporous resin HPD450 then, be washed to clarification, with 6 times of volume eluting of 30% ethanol, use 8 times of volume eluting of ethanol of 70% then, collect eluent, be concentrated into every ml and contain medical material 12g, Cryoprecipitation is standby;
(2) get Radix Paeoniae and add 8 times of water gagings extractions 2 times, extracted 1.5 hours at every turn, concentrate, add ethanol and reach 60%, put heavy 24 hours, filter to containing the alcohol amount, go up macroporous resin HPD100 then, wash with water, ammonia eluting with 1% to clarification, be washed to neutrality, with 3 times of volume eluting of 40% ethanol, use 10 times of volume eluting of ethanol of 50% then, collect eluent, be concentrated into every ml and contain medical material 10g, Cryoprecipitation is standby;
(3) get Rhizoma Chuanxiong and add 60% alcohol reflux 2 times, add 6 times of amounts of ethanol at every turn and extracted 1.5 hours, reclaim ethanol, concentrate, add ethanol to 75%, put heavy 24 hours, filter, polyamide column then, wash with water, continue, collect eluent with 8 times of volume eluting of 20% ethanol, be concentrated into every ml and contain medical material 10g, it is standby to add water water precipitating 24 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, lyophilization, aseptic subpackaged, check, promptly.
Embodiment 7
Radix Astragali 100g Rhizoma Chuanxiong 50g Radix Paeoniae 50g
(1) gets the Radix Astragali and add 50% alcohol reflux 2 times, add 5 times of amounts of ethanol at every turn and extracted 1.5 hours, reclaim ethanol, change water liquid over to and put heavy 48 hours, filter, last low pole macroporous resin HPD100 washes with water to clarification, with 4 times of volume eluting of 40% ethanol, use 4 times of volume eluting of ethanol of 50% then, collect eluent, be concentrated into every ml and contain medical material 10g, Cryoprecipitation is standby;
(2) get Radix Paeoniae and add 6 times of water gagings extractions 2 times, extracted 2.5 hours at every turn, concentrate, add ethanol and reach 60%, put heavy 24 hours, filter to containing the alcohol amount, go up macroporous resin AB-8 then, be washed to clarification, ammonia eluting with 2%, be washed to neutrality, 4 times of volume eluting of 40% ethanol are used 6 times of volume eluting of ethanol of 60% then, collect eluent, be concentrated into every ml and contain medical material 8g, Cryoprecipitation is standby;
(3) get Rhizoma Chuanxiong and add 75% alcohol reflux 2 times, add 8 times of amounts of ethanol at every turn and extracted 2 hours, reclaim ethanol, concentrate, add ethanol to 75%, put heavy 48 hours, filter, polyamide column then, wash with water, continue, collect eluent with 3 times of volume eluting of 40% ethanol, be concentrated into every ml and contain medical material 10g, it is standby to add water water precipitating 48 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, the fill lyophilization, check, promptly.
Embodiment 8
Radix Astragali 100g Rhizoma Chuanxiong 50g Radix Paeoniae Rubra 50g
(1) gets the Radix Astragali and add 50% alcohol reflux 2 times, add 5 times of amounts of ethanol at every turn and extracted 1.5 hours, reclaim ethanol, change water liquid over to and put heavy 48 hours, filter, last low pole macroporous resin HPD100 washes with water to clarification, with 4 times of volume eluting of 40% ethanol, use 4 times of volume eluting of ethanol of 50% then, collect eluent, be concentrated into every ml and contain medical material 10g, Cryoprecipitation is standby;
(2) get Radix Paeoniae Rubra and add 6 times of water gagings extractions 2 times, extracted 2.5 hours at every turn, concentrate, add ethanol and reach 60%, put heavy 24 hours, filter to containing the alcohol amount, go up macroporous resin AB-8 then, be washed to clarification, ammonia eluting with 2%, be washed to neutrality, 4 times of volume eluting of 40% ethanol are used 6 times of volume eluting of ethanol of 60% then, collect eluent, be concentrated into every m and contain medical material 8g, Cryoprecipitation is standby;
(3) get Rhizoma Chuanxiong and add 75% alcohol reflux 2 times, add 8 times of amounts of ethanol at every turn and extracted 2 hours, reclaim ethanol, concentrate, add ethanol to 75%, put heavy 48 hours, filter, polyamide column then, wash with water, continue, collect eluent with 3 times of volume eluting of 40% ethanol, be concentrated into every ml and contain medical material 10g, it is standby to add water water precipitating 48 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Rubra Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, the fill lyophilization, check, promptly.
Embodiment 9
Radix Astragali 200g Rhizoma Chuanxiong 100g Radix Paeoniae Rubra 30g
(1) gets the Radix Astragali and add 65% alcohol reflux 2 times, add 6 times of amounts of ethanol at every turn and extracted 2 hours, reclaim ethanol, change water liquid over to and put heavy 48 hours, filter, go up low pole macroporous resin HPD450 then, be washed to clarification, with 6 times of volume eluting of 30% ethanol, use 8 times of volume eluting of ethanol of 70% then, collect eluent, be concentrated into every ml and contain medical material 12g, Cryoprecipitation is standby;
(2) get Radix Paeoniae Rubra and add 8 times of water gagings extractions 2 times, extracted 1.5 hours at every turn, concentrate, add ethanol and reach 60%, put heavy 24 hours, filter to containing the alcohol amount, go up macroporous resin HPD100 then, wash with water, ammonia eluting with 1% to clarification, be washed to neutrality, with 3 times of volume eluting of 40% ethanol, use 10 times of volume eluting of ethanol of 50% then, collect eluent, be concentrated into every ml and contain medical material 10g, Cryoprecipitation is standby;
(3) get Rhizoma Chuanxiong and add 60% alcohol reflux 2 times, add 6 times of amounts of ethanol at every turn and extracted 1.5 hours, reclaim ethanol, concentrate, add ethanol to 75%, put heavy 24 hours, filter, polyamide column then, wash with water, continue, collect eluent with 8 times of volume eluting of 20% ethanol, be concentrated into every ml and contain medical material 10g, it is standby to add water water precipitating 24 hours;
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Rubra Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, lyophilization, aseptic subpackaged, check, promptly.
Claims (11)
1, a kind of injection for the treatment of cardiovascular and cerebrovascular disease is characterized in that preparing its consisting of of each raw material:
Radix Astragali 2-40 weight portion Rhizoma Chuanxiong 2-20 weight portion Radix Paeoniae 2-20 weight portion.
2, injection as claimed in claim 1 is characterized in that each raw material consists of:
Radix Astragali 4-20 weight portion Rhizoma Chuanxiong 3-10 weight portion Radix Paeoniae 3-10 weight portion.
3, injection as claimed in claim 1 is characterized in that each raw material consists of:
The Radix Astragali 10 weight portion Rhizoma Chuanxiongs 5 weight portion Radix Paeoniaes 5 weight portions.
4,, it is characterized in that described Radix Paeoniae is a Radix Paeoniae Rubra as the described injection of claim 1-3.
5,, it is characterized in that described injection pH value is between 4.0～9.0 as the described injection of claim 1-4.
6,, it is characterized in that described injection is powder pin, liquid drugs injection or transfusion as the described injection of claim 1-5.
7,, it is characterized in that the extraction process for purification of the Radix Astragali is according to the described injection of claim 1-6:
Get alcohol reflux 1-3 time that the Radix Astragali adds 45-80%, add ethanol 5-10 at every turn and doubly measure extraction 1-3 hour, reclaim ethanol, change water liquid over to and put heavy 24-72 hour, filter, go up macroporous resin then, wash with water, with 3-10 times of volume eluting of 20-40% ethanol to clarification, use the ethanol 4-10 times of volume eluting of 50-80% then, collect eluent, be concentrated into every ml and contain medical material 2-15g, Cryoprecipitation is standby.
8,, it is characterized in that the extraction process for purification of the Radix Astragali is according to the described injection of claim 1-6:
Get alcohol reflux 1-3 time that the Radix Astragali adds 45-80%, add ethanol 5-10 at every turn and doubly measure and extracted 1-3 hour, reclaim ethanol, concentrate, transfer pH value, put cold to 7-10, add hydrochloric acid to PH be 1-5, put heavy 24-72 hour, filter, go up macroporous resin then, wash with water, with 3-10 times of volume eluting of 20-40% ethanol to clarification, use the ethanol 4-10 times of volume eluting of 50-80% then, collect eluent, be concentrated into every ml and contain medical material 2-15g, Cryoprecipitation is standby.
9,, it is characterized in that the extraction process for purification of Radix Paeoniae Rubra is according to the described injection of claim 1-6:
Get Radix Paeoniae Rubra and add 4-10 times of water gaging extraction 1-3 time, extracted 1-3 hour at every turn, concentrate, add ethanol and reach 50-80%, put heavy 24-48 hour, filter to containing the alcohol amount, go up macroporous resin then, wash with water, with the ammonia eluting of 0.5-5% to clarification, be washed to neutrality, with 3-10 times of volume eluting of 20-40% ethanol, use the ethanol 4-10 times of volume eluting of 50-80% then, collect eluent, be concentrated into every ml and contain medical material 2-15g, Cryoprecipitation is standby.
10,, it is characterized in that the extraction process for purification of Rhizoma Chuanxiong is according to the described injection of claim 1-6:
Get alcohol reflux 1-3 time that Rhizoma Chuanxiong adds 45-80%, add ethanol 5-10 at every turn and doubly measure and extracted 1-3 hour, reclaim ethanol, concentrate, add ethanol to 70-80%, put heavy 24-48 hour, filter, polyamide column then, wash with water, continue, collect eluent with 3-10 times of volume eluting of 20-40% ethanol, be concentrated into every ml and contain medical material 2-15g, it is standby to add water water precipitating 24-72 hour.
11,, it is characterized in that the preparation method of this medicine is according to the described injection of claim 1-10:
Get Radix Astragali Cryoprecipitation liquid, Radix Paeoniae Rubra Cryoprecipitation liquid, Rhizoma Chuanxiong Cryoprecipitation liquid filters, and mixing adds the dissolving of injection water and is assigned to full dose, filters, fine straining, embedding sterilization or lyophilization are aseptic subpackaged, check, promptly.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101055318A CN100496543C (en) | 2005-09-27 | 2005-09-27 | Injection for treating cardiac cerebrovascular disease and its preparation |
| HK07108655A HK1100901A1 (en) | 2005-09-27 | 2007-08-09 | Injection for treating cardiovascular and cerebrovascular diseases and the process for preparing the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101055318A CN100496543C (en) | 2005-09-27 | 2005-09-27 | Injection for treating cardiac cerebrovascular disease and its preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1939432A true CN1939432A (en) | 2007-04-04 |
| CN100496543C CN100496543C (en) | 2009-06-10 |
Family
ID=37958134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005101055318A Expired - Fee Related CN100496543C (en) | 2005-09-27 | 2005-09-27 | Injection for treating cardiac cerebrovascular disease and its preparation |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN100496543C (en) |
| HK (1) | HK1100901A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102940702A (en) * | 2012-10-31 | 2013-02-27 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
-
2005
- 2005-09-27 CN CNB2005101055318A patent/CN100496543C/en not_active Expired - Fee Related
-
2007
- 2007-08-09 HK HK07108655A patent/HK1100901A1/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102940702A (en) * | 2012-10-31 | 2013-02-27 | 成都医路康医学技术服务有限公司 | Medicine composition for treating cardia-cerebrovascular diseases |
Also Published As
| Publication number | Publication date |
|---|---|
| HK1100901A1 (en) | 2007-10-05 |
| CN100496543C (en) | 2009-06-10 |
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