Technology contents
Purpose of the present invention just provides the Folium Crataegi injection that is used for the treatment of cardiovascular disease that a kind of pharmacological action is strong, therapeutic effect is good.
The object of the present invention is achieved like this: be used for the treatment of the Folium Crataegi injection of cardiovascular disease, and formulated by Folium Crataegi extract and solvent for injection, contain the total flavones of effective therapeutic dose in its solution.The contained total flavones of the every ml soln of its injection is in vitexin rhamnoside, and preferred value is 0.2-30mg.
Injection can be made injectable powder in the preparation, also can make aqueous injection.Aqueous injection can directly add the glucose solution iv drip of normal saline or 5-10% in use.Make injectable powder and can add the glucose solution iv drip that joins normal saline or 5-10% behind a small amount of water for injection or the physiological saline solution more in use earlier.
Injection of the present invention, used Folium Crataegi extract preferably select for use its general flavone content to should be the raw material of 80--98% in vitexin rhamnoside, to guarantee the quality of injection better.
In like manner, the Folium Crataegi extract Folium Crataegi extract of preferably selecting for use vitexin rhamnoside to account for the 30-50% of total flavones is a raw material.
Injection of the present invention, used injection solvent can be that normal saline also can be the glucose solution of 5-10%, but preferably select water for injection for use.Can make its preparation simpler like this, capability and performance is more stable when storage.
For guaranteeing that the Folium Crataegi injection has good beneficial effect, vitexin rhamnoside is controlled at 1.8~2.2: 1 with the ratio of vitexin glucoside HPLC Se Putu peak area in the injection of the present invention.
The preparation method of injection of the present invention is:
Get Folium Crataegi, add the lixiviate of 40-60% ethanol, filter, reclaim ethanol, being concentrated into relative density is 1.12-1.14 (50 ℃) thin up, cold preservation 12-24 hour, draw supernatant, lower floor filters, filtrate and supernatant merge, by macroporous adsorptive resins, with distilled water, alcoholic solution difference eluting, to alpha-Naphthol strong sulfuric acid response feminine gender.Collect this ethanol elution,, reclaim ethanol, when being concentrated into relative density and being 1.02-1.04 (50 ℃), put coldly, put in the separatory funnel, use ethyl acetate extraction to hydrochloric acid one magnesium powder reaction negative, extract reclaim ethyl acetate and be concentrated into dried, must extract I; Water layer continues use water saturated n-butanol extraction, and the recovery n-butyl alcohol also is concentrated into dried extract II; Extract II is dissolved in water and makes relative density is 1.02-1.04, and spray drying gets the used Folium Crataegi extract of the present invention.
Get above-mentioned Folium Crataegi extract, add the injection water, stirring and dissolving transfers pH value to 6.0-6.5, cold preservation, and cold preservation liquid filters, and filtrate adds activated carbon decolorizing and filters.Filtrate adds the injection water to the regulation labelled amount, stirs evenly, and embedding, 100 ℃ of water-bath sterilizations, promptly.
The content assaying method of injection of the present invention is:
The total flavones reference substance solution prepares precision and takes by weighing the vitexin rhamnoside reference substance to add Diluted Alcohol in right amount an amount of, ultrasonicly makes dissolving, makes the solution that every 1ml contains 0.20mg.
The preparation precision of standard curve is measured reference substance solution 1.0ml, 2.0ml, 3.0ml, 4.0ml, 5.0ml, 6.0ml, puts respectively in the 25ml measuring bottle, and the accurate successively 0.1mol/L aluminum chloride alcoholic solution 1ml that adds adds Diluted Alcohol and is diluted to scale, shakes up; With corresponding solution is blank, according to spectrophotography (appendix VA of Pharmacopoeia of the People's Republic of China version in 2000), measures trap at 277 ± 1nm wavelength place, be absorbed as vertical coordinate, concentration is abscissa, the drawing standard curve.
Algoscopy is got 1ml of the present invention, puts in the measuring bottle of 10ml, and thin up shakes up to scale.The accurate 1ml that draws puts in the 25ml measuring bottle, and the method under the sighting target directrix curve item is from " add 0.1mol/L aluminum trichloride solution 1ml, (appendix VA of Pharmacopoeia of the People's Republic of China version in 2000) measures trap " in accordance with the law.From the weight that standard curve is read vitexin rhamnoside the need testing solution, calculate, promptly.
The every 1ml of injection of the present invention contains total flavones with vitexin rhamnoside (C
27H
30O
14) meter, be 0.2-30mg.
The vitexin glucoside is measured according to high performance liquid chromatography (an appendix VI of Pharmacopoeia of the People's Republic of China version in 2000 D).
The test of chromatographic condition and system suitability with the octadecyl bonding mutually silica gel be filler; Waters, Symmetry post (3.9mm * 150mm, 3.5 μ); Isopropyl alcohol-oxolane-1% acetum (4: 16: 92.5) is a mobile phase; The detection wavelength is 340nm.Theoretical cam curve is calculated by vitexin rhamnoside should be not less than 2000.
It is an amount of that the vitexin rhamnoside reference substance is got in the preparation of reference substance solution, and accurate the title decides, and adds methanol and makes the solution that every 1ml contains vitexin rhamnoside 0.08mg, promptly.
The accurate absorption of the preparation of need testing solution 1ml of the present invention puts in the 10ml measuring bottle, and thin up shakes up to scale.The accurate 2ml that draws puts in the 5ml measuring bottle, and thin up shakes up to scale, promptly.
Accurate respectively reference substance solution and each the 5 μ l of need testing solution of drawing of algoscopy inject high performance liquid chromatograph, measure, promptly.
The every 1ml of injection of the present invention contains vitexin rhamnoside (C
27H
30O
14) be the 30-50% of total flavones.
Vitexin rhamnoside is 1.8~2.2: 1 with the ratio of vitexin glucoside HPLC Se Putu peak area among the present invention.
The usage and dosage of injection of the present invention is:
Intravenous drip, every day, consumption was that total flavones in the injection is with vitexin rhamnoside (C
27H
30O
14) 50-250mg, in the normal saline of adding 250ml or the glucose solution of 5-10%.
Injection of the present invention has no side effect through acute toxicity and long term toxicity test.Can strengthen or minimizing use amount every day according to the state of an illness clinical use Chinese physician.
Injection of the present invention can be used for blood circulation promoting and blood stasis dispelling, and a surname's numbness is promoted blood circulation.Cure mainly the type of obstruction of heart-blood thoracic obstruction, pained (ischemic heart desease and angina cordis), disease is seen chest distress, or has and lose heart, ambition pain, and as thorn as strand, localized pain, purplish tongue, or ecchymosis is arranged, or the Sublingual blood vessels are livid purple, and arteries and veins is dizzy puckery.
The important innovations part of injection of the present invention is that this injection has significantly improved the drug effect and the therapeutic effect of Folium Crataegi preparation.Particularly when it is used for the treatment of cardiovascular disease, not only obviously coronary blood flow increasing, coronary artery dilator blood vessel, reduce coronary resistance, but also can increase cardiac output and heartbeat output, can reduce simultaneously arterial oxygen content, increase venous oxygen content, reduce myocardial oxygen consumption and myocardium coefficient of oxygen utilization, improve the blood supply oxygen supply of cardiac muscle, and can reduce total peripheral resistance.So when it is used for the treatment of disease such as myocardial ischemia, myocardial infarction, have better beneficial effect.
Beneficial effect of the present invention has obtained confirmation by following experiment.
Laboratory animal: 30 of healthy adult dogs, the male and female dual-purpose, body weight 16.08 ± 2.12kg cultures factory by Beijing's tonneau laboratory animal [word (2000) is moved No. 010 in the capital] is provided.
The experiment medicine: injection of the present invention: 5ml/ props up, and 10mg/ml is provided by pharmacy chamber, Xiyuan Hospital, Chinese Medicine Academy of China experimentation center; Yixintong is pressed the preparation of the Pharmacopoeia of the People's Republic of China (2000 editions 1 one) Yixintong piece preparation method by Xiyuan Hospital, Chinese Medicine Academy of China's experimentation center pharmacy.
Experiment is divided into 3 groups: (1) blank group, normal saline 1ml/kg; (2) injection 10mg/kg dosage group of the present invention.More than n=12 before two groups of 60min, n=6 in the time of 90 to 120min.(3) Yixintong 100mg/kg dosage group, n=6.Above-mentioned experiment medicine is mixed with same volume (50ml) with normal saline, and computer micro-injection pump (AJ-5803 type, Shanghai) feeds institute's reagent thing with the speed of 5ml/min through femoral vein.
Experimental technique:
Laboratory animal pentobarbital sodium (30mg/kg) intravenous anesthesia, tracheal intubation connects electronic artificial respiration (SC-3 type, Shanghai).Execute left side the 4th intercostal thoracotomy, expose heart, cut off pericardium, make the pericardium bed, separate LCA and aortic root, place electromagnetic flowmeter (MF-1100 type, Japanese photoelectricity) probe, measure coronary flow and cardiac output respectively.Left ventricle tip intubate connects pressure transducer (MPU-0.5A), measures left indoor pressure through carrier amplifier (AP-601G), calculates left indoor pressure rising maximum rate (dp/dt through differentiator (ED-601G) again
Max).The external jugular vein intubate is to coronary sinus vein, the carotid artery intubate, and (AVL912 type, Switzerland) measures coronary sinus vein oxygen content, calculating myocardium oxygen consumption respectively with blood oxygen instrument.Femoral arteriography is measured arteriotony, leads electrocardiogram with limb lead observation standard I I and calculates heart rate and relevant electrocardiogram parameter.Calculate other hemodynamic index: cardiac output, oxygen consumption index, coronary resistance, total peripheral resistance and coefficient of oxygen utilization etc.With above-mentioned every index synchronous recording in polygraph (RM-6000 type, Japanese photoelectricity).
Operation finishes, treat that observed index is stable after, value before the record medicine feeds the reagent thing.And in medicine behind 5min, the medicine at once, behind the medicine 1,3,5,10,15,30,60,90,120min carries out record.Before the medicine, behind the medicine at once behind the medicine 5,15,45,60,90,120min measures tremulous pulse, coronary sinus vein oxygen content, calculating myocardium oxygen consumption.Every observation index and derivation parameter are carried out statistical procedures, carry out administration with the measured values of different observing times before and after self relatively, its change percentage rate organize between relatively, judge its significance with the t check.
Experimental result
Influence to dog cardiac output, heartbeat output
The results are shown in Table 1, continuous table 1, table 2, continuous table 2, Fig. 1, Fig. 2.
Each administration group of table 1. is to the influence of dog cardiac output (L/min) (before the medicine~medicine after 10min) X ± SD
Behind the preceding value of the dosage medicine medicine (min)
In the group medicine behind the 5min medicine at once
/ kg rate of change 135 10
Normal saline 1ml 1.108 ± 0.352 1.113 ± 0.361 1.095 ± 0.375 1.094 ± 0.389 1.066 ± 0.410 1.078 ± 0.400 1.084 ± 0.346
(n=12) 100.31±3.74 98.04±7.38 97.63±6.45 94.37±13.75 95.86±14.40 97.77±4.02
Injection 10mg 1.421 of the present invention ± 0.503 1.507 ± 0.529##, 1.550 ± 0.499##, 1.548 ± 0.499#, 1.580 ± 0.498##, 1.603 ± 0.525##, 1.618 ± 0.505##
(n=12) 106.26±4.61
**110.38±11.50
*110.32±12.61
*112.82±15.40
* 114.12±13.64
*?115.97±14.52
***
Yixintong 10mg 1.145 ± 0.223 1.143 ± 0.631 1.187 ± 0.189# 1.183 ± 0.215 1.193 ± 0.251## 1.188 ± 0.213 1.217 ± 0.175#
(n=6) 100.10±46.75 104.37±5.70
*?103.80±6.90
*?104.00±4.55
*** 104.33±8.08
* 107.71±13.49
Continuous each administration group of table 1. is to the influence of dog cardiac output (L/min) (X ± SD of 15min behind the medicine~120min)
Behind the dosage medicine (min)
Group
/kg 15 30 45 60 90(n=6) 120(n=6)
Normal saline 1ml 1.098 ± 0.351 1.083 ± 0.358 1.062 ± 0.340# 1.084 ± 0.340 1.062 ± 0.335#, 1.068 ± 0.348#
(n=12) 99.00±4.86 97.20±6.39 95.61±7.76 97.88±6.67 89.84±10.94 90.15±12.19
Injection 10mg 1.613 ± 0.529## 1.557 ± 0.510# 1.483 ± 0.524 1.428 ± 0.528 1.645 ± 0.556 1.598 ± 0.610 of the present invention
(n=12) 115.08±15.19
**?111.35±15.16
* 105.60±15.26 101.42±13.72 100.91±17.33 97.23±19.01
Yixintong 10mg 1.230 ± 0.263# 1.167 ± 0.272 1.112 ± 0.290 1.058 ± 0.243 0.902 ± 0.168## 0.873 ± 0.174
(n=6) 107.61±9.07
* 102.11±16.75 97.15±19.89 92.88±16.32 79.61±12.19 76.78±11.90
*
Annotate: compare with matched group: * P<0.05, * * P<0.01, * * *: P<0.001; The preceding comparison of self medicine: #P<0.05, ##P<0.01, ###P<0.001
Each administration group of table 2. is to the influence of dog cardiac output (ml/beat) (before the medicine~medicine after 10min) X ± SD
Behind the preceding value of the dosage medicine medicine (min)
In the group medicine behind the 5min medicine at once
/ kg rate of change 135 10
Normal saline 1ml 6.303 ± 1.782 6.397 ± 1.930 6.313 ± 2.031 6.293 ± 2.067 6.159 ± 2.231 6.287 ± 2.136 6.295 ± 1.784
(n=12) 101.01±5.99 99.29±11.34 98.68±8.88 95.90±17.10 98.59±18.79 100.01±10.09
Injection 10mg 8.243 of the present invention ± 2.913 8.930 ± 3.107###, 9.178 ± 2.967###, 9.173 ± 3.154##, 9.281 ± 3.138##, 9.444 ± 3.279##, 9.553 ± 3.261##
(n=12) 109.05±4.97
**?112.91±10.17
*112.26±12.02
*113.65±15.56
*115.41±14.51
*117.55±15.28
**
Yixintong 10mg 8.759 ± 0.982 8.988 ± 1.139 9.140 ± 1.575 9.102 ± 1.158 9.105 ± 1.242 9.175 ± 1.565 9.353 ± 1.748
(n=6) 102.97±11.24 104.58±14.79 104.40±12.53 104.27±11.38 104.80±12.94 106.85±15.88
**
Continuous each administration group of table 2. is to the influence of dog cardiac output (ml/beat) (X ± SD of 15min behind the medicine~120min)
Behind the dosage medicine (min)
Group
/kg 15 10 45 60 90(n=6) 120(n=6)
Normal saline 1ml 6.349 ± 1.884 6.189 ± 1.920 6.117 ± 1.812 6.215 ± 1.760 5.793 ± 893##, 5.857 ± 836##
(n=12) 100.51±10.04 97.43±8.90 96.65±9.55 98.67±9.01 88.18±12.03 89.41±10.54
Injection 10mg 9.477 ± 3.138## 9.286 ± 3.266# 8.778 ± 3.453 8.445 ± 3.452 9.729 ± 4.004 9.456 ± 4.373 of the present invention
(n=12) 116.59±15.71
*114.19±16.20
*107.12±15.59?102.59±13.03 102.69±17.59 99.07±21.27
Yixintong 10mg 9.505 ± 1.762 9.178 ± 1.732 8.834 ± 1.742 8.274 ± 1.590 7.918 ± 1.945 7.487 ± 1.799#
(n=6) 108.89±17.63 105.47±19.99 101.33±18.73?94.91±16.87 90.72±20.07 85.92±19.28
Annotate: compare with matched group: * P<0.05, * * P<0.01, * * *: P<0.001; The preceding comparison of self medicine: #P<0.05, ##P<0.01, ###P<0.001
The result shows: injection intravenously administrable of the present invention can make cardiac output obviously increase, and 5min lasts till 30min behind the medicine in the self administration of medication process, and kinemic increasing degree is about 15%.Yixintong also can partly increase cardiac output, but action intensity is lower than injection of the present invention.Injection of the present invention can make cardiac output obviously increase simultaneously, and the persistent period is approximately 10min, and increasing degree is about 10%.
Influence to the dog total peripheral resistance
The results are shown in Table 3, continue table 3, Fig. 3.
Each administration group of table 3. is to dog total peripheral resistance (mmHg/Lmin
1) influence (before the medicine~medicine after 10min) X ± SD
Behind the preceding value of the dosage medicine medicine (min)
In the group medicine behind the 5min medicine at once
/ kg rate of change 135 10
Normal saline 1ml 10572.4 ± 2747.4 10472.4 ± 2776.9 10840.5 ± 3153.4 10861.0 ± 3153.6 11788.8 ± 5555.6 11653.3 ± 5982.7 10799.5 ± 2799.7
(n=12) 99.26±6.65 102.12±8.11 102.17±6.85 108.88±24.29 107.23±27.95 102.38±4.49
Injection 10mg 9508.7 of the present invention ± 2975.8 8786.6 ± 3014.0###, 8645.5 ± 2872.5#, 8603.6 ± 2756.4##, 8450.9 ± 2978.1#, 8296.0 ± 2751.7###, 8242.9 ± 2785.5###
(n=12) 91.78±5.10
* 91.17±8.47
* 90.96±7.98
** 88.93±9.56
* 87.32±7.22
* 86.50±6.91
***
Yixintong 10mg 9170.8 ± 1353.5 9058.7 ± 1416.7 9263.7 ± 1869.9 9346.9 ± 1721.2 9533.5 ± 1754.1 9627.0 ± 1653.8 9691.4 ± 1425.5#
(n=6) 99.14±9.93 101.27±15.51 102.31±14.43 104.22±14.06 105.15±11.46 105.97±8.16
Continuous each administration group of table 3. is to dog total peripheral resistance (mmHg/Lmin
-1) the influence (X ± SD of 15min behind the medicine~120min)
Behind the dosage medicine (min)
Group
/kg 15 30 45 60 90(n=6) 120(n=6)
Normal saline 1ml 10505.5 ± 2803.0 11106.6 ± 3580.8 11319.7 ± 3489.0# 10851.6 ± 3414.6 10744.0 ± 2928.8 10612.4 ± 3112.5
(n=12) 99.47±5.94 104.03±9.02 106.27±8.93 101.52±6.69 102.87±6.07 101.17±6.29
Injection 10mg 8309.4 ± 2904.9### 8439.9 ± 2939.0### 8995.7 ± 3239.7 9389.3 ± 3504.2 7499.2 ± 2335.2 7795.0 ± 2569.6 of the present invention
(n=12) 86.89±8.07
*** 88.20±8.26
*** 93.60±9.82
* 97.52±13.82 96.99±17.15 101.02±21.23
Yixintong 10mg 9192.6 ± 1000.6 9197.2 ± 972.6 9345.6 ± 1258.0 9769.0 ± 1176.1 10601.5 ± 1539.7 11370.4 ± 1830.0
(n=6) 101.07±9.04 102.05±17.66 103.65±19.41 108.09±17.18 117.44±21.58 126.49±28.07
*
Annotate: compare with matched group: * P<0.05, * * P<0.01, * * *: P<0.001; The preceding comparison of self medicine: #P<0.05, ##P<0.01, ###P<0.001
The result shows: injection of the present invention can make total peripheral resistance reduce, and improves the peripheral blood supply, and 5min lasts till 30min behind the medicine in the self administration of medication process, total peripheral resistance than medicine before and matched group significant difference (P<0.05-0.001) is more all arranged.Yixintong does not have obvious influence to Peripheral resistance.
Influence to dog arterial oxygen content, venous oxygen content
The results are shown in Table 4, table 5, Fig. 4, Fig. 5.
Each administration group of table 4. is to the X ± SD that influences of dog arterial oxygen content (g/100ml)
Behind the preceding value of the dosage medicine medicine (min)
Behind the group medicine at once
/ kg rate of change 5 15 30 60 90 (n=6) 120 (n=6)
Normal saline 1ml 11.41 ± 2.97 11.33 ± 2.97 11.31 ± 2.86 11.50 ± 3.01 11.42 ± 2.89 11.20 ± 3.04 9.52 ± 2.69 9.62 ± 3.13
(n=12) 99.41±5.41 99.55±4.63 101.10±5.80 100.39±4.79?98.29±7.43 100.80±8.57 100.99±12.36
The present invention's injection
Liquid 10mg 11.88 ± 1.82 10.94 ± 1.72# 11.48 ± 1.91 11.65 ± 1.97 11.66 ± 1.99 11.82 ± 2.25 12.12 ± 2.46 11.98 ± 2.36
(n=12) 92.44±8.01
*?96.71±7.22 98.17±8.47 98.30±9.17 99.44±11.03?102.16±14.85?101.37±16.93
Yixintong 10mg 7.67 ± 2.72 7.80 ± 2.38 7.90 ± 2.31 7.85 ± 2.15 7.88 ± 2.41 7.60 ± 2.42 7.60 ± 2.15 7.55 ± 2.31
(n=6) 104.03±10.34?105.99±12.58?105.38±11.14?104.64±7.44?100.41±7.86?101.54±10.34?99.89±6.02
Annotate: compare with matched group: * P<0.05, * * P<0.01, * * *: P<0.001; The preceding comparison of self medicine: #P<0.05, ##P<0.01, ###P<0.001
Each administration group of table 5. is to the X ± SD that influences of dog venous oxygen content (g/100ml)
Behind the preceding value of the dosage medicine medicine (min)
Behind the group medicine at once
/ kg rate of change 5 15 30 60 90 (n=6) 120 (n=6)
Normal saline 1ml 5.59 ± 3.12 5.37 ± 2.91 5.26 ± 2.78 5.19 ± 2.96#, 5.10 ± 3.04#, 5.08 ± 2.96##, 2.22 ± 1.12# 2.40 ± 1.49
(n=12) 100.34±14.96 97.84±12.88 94.66±11.67 91.97±21.05 91.80±16.61 85.29±30.37 88.02±30.58
The present invention's injection
Liquid 10mg 2.78 ± 1.35 3.67 ± 2.12##, 3.98 ± 1.89###, 4.08 ± 1.74###, 4.37 ± 1.77###, 4.13 ± 1.77##, 3.77 ± 1.80##, 3.88 ± 1.72##
(n=12) 127.62±24.13
*147.93±34.06
***153.36±26.62
***168.91±45.85
***157.51±48.32
***167.07±61.50
* 180.93±68.89
*
Yixintong 10mg 2.35 ± 1.21 2.82 ± 1.10 2.92 ± 1.81 3.18 ± 2.34 3.28 ± 2.41 3.27 ± 2.55 3.10 ± 2.10 2.95 ± 2.090
(n=6) 138.21±63.99 131.86±74.26 144.09±102.97 147.15±103.89 146.68±109.91 135.77±83.92 130.74±88.58
Annotate: compare with matched group: * P<0.05, * * P<0.01, * * *: P<0.001; The preceding comparison of self medicine: #P<0.05, ##P<0.01, ###P<0.001
The result shows: behind the normal saline matched group medicine animal arterial oxygen content is not had obvious influence; Injection of the present invention all has certain reduction effect Yixintong that arterial oxygen content is not had obvious influence to the animal arterial oxygen content.
Behind the normal saline matched group medicine 15 to 60 minutes the time animal venous oxygen content decrease; Injection of the present invention has obvious rising effect to the animal venous oxygen content, and drug action may persist to behind the medicine 120 minutes.Yixintong also has rising trend to venous oxygen content, but with the matched group no significant difference.
Influence to dog myocardial oxygen consumption and coefficient of oxygen utilization
The results are shown in Table 6, table 7, Fig. 6, Fig. 7.
Each administration group of table 6. is to dog myocardial oxygen consumption (ml/100gmin
-1) influence X ± SD
Behind the preceding value of the dosage medicine medicine (min)
Behind the group medicine at once
/ kg rate of change 5 15 30 60 90 (n=6) 120 (n=6)
Normal saline 1ml 5.19 ± 2.36 5.29 ± 2.51 5.37 ± 2.31 5.56 ± 2.79 5.44 ± 2.62 5.19 ± 2.39 5.69 ± 2.48 5.61 ± 2.57
(n=12) 101.36±7.54 104.31±7.47 105.29±8.40 104.13±12.43 100.15±7.72 101.00±11.49?98.83±14.04
The present invention's injection
Liquid 10mg 8.44 ± 2.22 6.86 ± 2.22#, 7.23 ± 1.89#, 7.22 ± 2.03#, 6.80 ± 1.59##, 7.05 ± 1.76## 7.94 ± 1.46 7.26 ± 1.05
(n=12) 82.21±19.86
*86.86±16.92
*86.39±18.37
*81.97±12.50
***84.85±14.95
*89.92±21.47 82.44±18.61
Yixintong 10mg 5.50 ± 2.62 5.12 ± 1.16 5.32 ± 1.31 5.27 ± 1.79 5.06 ± 1.37 4.59 ± 1.39 4.70 ± 1.25 4.98 ± 1.13
(n=6) 100.70±23.56?107.07±35.72?111.18±46.08?105.31±40.27 97.08±37.93 99.27±42.55 106.52±43.93
Annotate: compare with matched group: * P<0.05, * * P<0.01,
* *: P<0.001; The preceding comparison of self medicine: #P<0.05, ##P<0.01, ###P<0.001
Each administration group of table 7. to dog coefficient of oxygen utilization (%) influence X ± SD
Behind the preceding value of the dosage medicine medicine (min)
Behind the group medicine at once
/ kg rate of change 5 15 30 60 90 (n=6) 120 (n=6)
Normal saline 1ml 38.10 ± 6.86 54.88 ± 18.06 55.99 ± 17.67 57.23 ± 19.25# 57.81 ± 2,007 57.57 ± 1906# 77.33 ± 6.80 76.58 ± 7.68
(n=12) 103.34±11.59 105.83±11.32 107.24±11.82 108.31±12.69 107.99±8.39 108.69±11.88?107.33±9.74
The present invention's injection
Liquid 10mg 74.74 ± 9.28 67.37 ± 17.16##, 65.89 ± 13.63###, 65.31 ± 13.19###, 62.82 ± 13.00###, 65.15 ± 13.67##, 69.65 ± 12.86#, 68.04 ± 11.87##
(n=12) 86.21±15.00
*?84.78±9.48
***?84.16±10.08
***81.10±11.47
***84.22±12.52
***?86.87±11.18
*84.96±11.08
**
Yixintong 10mg 69.95 ± 11.84 64.72 ± 6.96 65.63 ± 13.76 63.05 ± 18.58 62.40 ± 17.58 61.41 ± 19.91 62.75 ± 17.63 64.59 ± 16.69
(n=6) 94.29±14.94 94.80±17.26 92.02±26.58 90.87±24.88 89.55±28.52 90.86±23.44 94.32±25.16
Annotate: compare with matched group: * P<0.05, * * P<0.01, * * *: P<0.001; The preceding comparison of self medicine: #P<0.05, ##P<0.01, ###P<0.001
The result shows: myocardial oxygen consumption does not have significant change behind the normal saline matched group medicine; Injection of the present invention has obvious reduction effect drug effect to the animal cardiac muscle oxygen consumption and may persist to behind the medicine 90 minutes; Yixintong does not have obvious influence to the animal cardiac muscle oxygen consumption.
The normal saline matched group does not have obvious influence to the animal coefficient of oxygen utilization; Injection of the present invention has obvious reduction effect to the animal coefficient of oxygen utilization; Yixintong does not have obvious influence to coefficient of oxygen utilization.
Above experimental result shows that injection of the present invention can obviously increase hat blood flow volume, coronary artery dilator blood vessel, reduce coronary resistance, increase cardiac output and cardiac output, reduce arterial oxygen content, increase venous oxygen content, and can reduce total peripheral resistance; And Yixintong does not have obvious influence to cardiac output, cardiac output and heart metabolism.
Both main distinctions are that injection of the present invention improves significantly to the blood ability of penetrating, the oxygen metabolism effect tool of heart, can significantly increase cardiac output and cardiac output, reduce arterial oxygen content, increase venous oxygen content, reduce myocardial oxygen consumption and myocardium coefficient of oxygen utilization, improve the blood supply oxygen supply of cardiac muscle.
This shows that improving aspect cardiac hemodynamic and the myocardial oxygen consumption, injection of the present invention significantly is better than Yixintong.