CN101940778B - Medicinal composition for treating heart failure and preparation method and application thereof - Google Patents
Medicinal composition for treating heart failure and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a medicinal composition for treating heart failure. The medicinal composition is prepared from the following raw materials in part by weight: 2 parts of prepared common monkshood daughter root total alkaloid and 1 part of dried ginger extract. The invention also provides a preparation method and application of the medicinal composition. The prepared common monkshood daughter root total alkaloid is not only the main toxic component but also the main active ingredient of prepared common monkshood daughter root for recuperating depleted yang, and the toxicity and the medicinal effect have a close relationship. When the ratio of the prepared common monkshood daughter root total alkaloid to the dried ginger extract is 2:1, the medicinal composition has the effects of reducing the toxicity and increasing the medicinal effect, has definite medicinal effect and low toxicity and is a new choice for clinical application.
Description
The application is an application number: the dividing an application of 200710187765.0 patent application.The original application application number: 200710187765.0, the applying date: on November 23rd, 2007, denomination of invention: a kind of pharmaceutical composition for the treatment of heart failure and its production and use.
Technical field
The present invention relates to a kind of pharmaceutical composition for the treatment of heart failure, belong to drug world.
Background technology
Radix Aconiti Lateralis Preparata compatibility Rhizoma Zingiberis be Chinese medicine clinical practice frequency at all times very high to medicine, Radix Aconiti Lateralis Preparata Rhizoma Zingiberis soup, head see " a Treatise on Febrile Diseases TAI YANG syndrome piece of writing ".The hot Wen Dare of Radix Aconiti Lateralis Preparata, " book on Chinese herbal medicine is through reading " day: " the warming the interior recuperating depleted YANG is stronger for acrid in the mouth temperature, fast of bad temper, and heart-yang is rouse oneself.Do not have institute less than, so be the recuperating depleted YANG and rescuing the patient from collapse first product medicine." the hot temperature of Rhizoma Zingiberis, " typhoid fever Yaoxing Fu " called it and " can be gone heavy cold ".Just because of Radix Aconiti Lateralis Preparata is walked and do not kept, Rhizoma Zingiberis is kept and does not walk, and both complementarity are extremely strong, and ancients have saying of " Radix Aconiti Lateralis Preparata not having Jiang Bure " again.Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis all can go into heart channel and return heart-yang, and heart-yang is rescued, and then god is more not outer, so there is recuperating depleted YANG not forget to control saying of the heart.In recent years, modern pharmacological research finds to have effects such as tangible heart tonifying, shock, microcirculation improvement based on the decoction for Resuscitation of Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis compatibility, illustrates that yang depletion syndrome is relevant with heart failure, shock, microcirculation disturbance etc.Clinically, Radix Aconiti Lateralis Preparata compatibility Rhizoma Zingiberis is also normal adds and subtracts application of treatment heart failure, myocardial infarction, shock, sinus bradycardia, acute pulmonary heart disease etc. with other medicine.
In the modern times clinical in, Radix Aconiti Lateralis Preparata is usually used in giving treatment to shock, hypotension state, coronary heart disease and the rheumatic heart disease etc. due to the acute myocardial infarction, and good curative effect is all arranged, this is all relevant with effect that it has cardiovascular aspects such as strengthening myocardial contraction, arrhythmia.Yang Fan, Lin Shuxin, Zhang Fuqin, Deng. the effect research [J] of river, Sichuan oil Radix Aconiti Lateralis Preparata extract anti-hemorrhagic shock. The Fourth Military Medical University's journal, 1996,17 (2): 116, show that the Radix Aconiti Lateralis Preparata water-soluble portion separates the effect that the uracil compounds that obtains has anti-hemorrhagic shock.Its main mechanism of action is to strengthen myocardial contraction, improves cardiac output and mean arterial blood pressure, and can improve shock back survival of rats rate.Zhang Mei, Zhang Yi, Chen Haihong, Deng. Radix Aconiti Lateralis Preparata arrhythmia active component research [J]. the time precious traditional Chinese medical science traditional Chinese medicines, 2000,11 (3): 193-194 shows the result of study of Radix Aconiti Lateralis Preparata arrhythmia active component, Radix Aconiti Lateralis Preparata n-butanol extract, ethanol extraction and water extract all quiver to chloroform induced mice chamber preventive effect, wherein obvious with the water extract effect especially.
Rhizoma Zingiberis is the medicine of warming the interior, have effects such as antalgic, warm promoting blood circulation, recuperating depleted YANG and rescuing the patient from collapse, warming spleen and stomach for dispelling cold, warming the lung to relieve cough, modern pharmacological research its easing pain and diminishing inflammation, antiallergic action, thromboembolism preventing anticoagulant arranged, regulate blood circulation, anti-hypoxia, town are told, digestion promoting, antidiarrheal, effect such as protect the liver.Wang Meng, Qian Hong U.S., Soviet Union is simple. Rhizoma Zingiberis ethanol extraction antipyretic-antalgic and external bacteriostasis research. and new Chinese medicine and clinical pharmacology, 2001,14 (5): 299-301, Deng employing mice auricular concha swelling method, TAB/VAC causes house to exempt from antiinflammatory, analgesic, the analgesic activity of exothermic reaction and mouse writhing method observation Rhizoma Zingiberis ethanol extract.
Zhu Linping. Radix Aconiti Lateralis Preparata toxicity research overview. the Jiangxi Chinese medicine, 2004,35 (6): 53-55, sum up from the toxic correlative factor of Radix Aconiti Lateralis Preparata, think that Radix Aconiti Lateralis Preparata toxicity and kind and picking season, the process of preparing Chinese medicine, dosage, decocting method and time, compatibility are improper, retention toxicosis etc. is relevant.The toxic effect relation of Radix Aconiti Lateralis Preparata is very close.Radix Aconiti Lateralis Preparata has tangible normal pressure resisting oxygen lack, and after Radix Aconiti Lateralis Preparata was removed toxic alkaloid, the normal pressure resisting oxygen lack weakened, even disappears; Radix Aconiti Lateralis Preparata also has stronger analgesic activity, and after Radix Aconiti Lateralis Preparata was removed toxic component, its analgesic activity obviously weakened.The contained aconitine of Radix Aconiti Lateralis Preparata is the most obvious to the toxicity of heart, and its mechanism one is excited vagus, and the 2nd, directly, cause arrhythmia to the toxic action of heart.Pharmacological testing confirms that alkaloid toxicity contained in the Radix Aconiti Lateralis Preparata is bigger, but toxic component is met heat energy and is decomposed, the immersion of long period and decoction can be hydrolyzed into it less benzoyl aconine of toxicity (Benzoylaconine) Alkaloid, and then be decomposed into the littler aconine of toxicity (Aconine) Alkaloid (Li Rongzong. the reasonable process of preparing Chinese medicine experience [J] of Radix Aconiti Lateralis Preparata, Radix Aconiti, Radix Aconiti Kusnezoffii. Strait Pharmaceutical Journal, 2001,13 (2): 49), thereby reduce its toxicity.JIANGFU matches, and except that the effect that can strengthen recuperating depleted YANG and rescuing the patient from collapse, tradition is thought the toxicity that can also reduce Radix Aconiti Lateralis Preparata.The prescription that relevant JIANGFU compatibility of successive dynasties is used for recuperating depleted YANG and rescuing the patient from collapse is more.Experimentation shows that Radix Aconiti Lateralis Preparata has tangible cardiovascular pharmacological effect, but heart tonifying, blood pressure lowering, blood vessel dilating, shock; The Rhizoma Zingiberis decoct does not then have tangible cardiotonic.The two compatibility, Rhizoma Zingiberis can make the Radix Aconiti Lateralis Preparata cardiotonic obviously strengthen (Xu Xinguo. the discussion that the classical prescription Radix Aconiti Lateralis Preparata is used. Beijing Journal of Traditional Chinese Medicine, 1986, (3): 33).Above-mentioned report all is the general goal square preparations that contain Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis, only do not use the relevant report of Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis compatibility, and owing to the active ingredient complexity in Radix Aconiti Lateralis Preparata, the Rhizoma Zingiberis, the position of the composition of performance drug effect is all uncertain, do not report that at present wherein the live part compatibility uses, and reaches the relevant report of attenuation synergistic yet.
Summary of the invention
Technical scheme of the present invention has provided a kind of pharmaceutical composition for the treatment of heart failure, and another technical scheme of the present invention has provided this preparation of drug combination method and purposes.
The invention provides a kind of pharmaceutical composition for the treatment of heart failure, it is the medicament that is prepared from by the following weight proportion raw material:
Radix Aconiti Lateralis Preparata total alkaloids 1-5 part, Rhizoma Zingiberis effective site 1-2 part, described Rhizoma Zingiberis effective site is Rhizoma Zingiberis extract, Rhizoma Zingiberis volatile oil.
Wherein, Rhizoma Zingiberis extract, general gingerol content is in capsaicin 15%w/w; Rhizoma Zingiberis volatile oil under the silica gel thin-layer chromatography spectral condition, is equipped with same blob with Rhizoma Zingiberis control medicinal material volatile oil in identical bits.
The extraction preparation method of Radix Aconiti Lateralis Preparata total alkaloids, Rhizoma Zingiberis extract, Rhizoma Zingiberis volatile oil can be extracted preparation by textbook or document disclosed method, as Xiao Chonghou. Chemistry for Chinese Traditional Medicine. and the .1997 of Shanghai science tech publishing house; Qiu Qin, Zhang Guoying, Liu Xinxin, etc. supercritical 2 fluid extraction methods and steam distillation extract the comparison of dried ginger slice chemical composition of volatile oil. journal of shanghai Chinese medicine .2005; 39 (3); Wang Meng, Qian Hong U.S., Soviet Union is simple. Rhizoma Zingiberis ethanol extraction antipyretic-antalgic and external bacteriostasis research, 2001; 14 (5): 299; Mature salt is given birth to, Lin Yulian. and Rhizoma Zingiberis and Rhizoma Zingiberis Preparatum volatile oil component are relatively. Nanjing University of Traditional Chinese Medicine's journal, 1999; 15 (6): 378; Yu Chenghao. the material base research that Aconitum carmichjaelii Debx. class toxic herb compatibility drug commonly used is right. 2006 grades of doctorate papers of Chengdu University of Traditional Chinese Medicine. the instructor, Peng becomes.
Wherein, in the described Radix Aconiti Lateralis Preparata total alkaloids, total alkaloid content is counted 100～150mg/ml with aconitine.Further preferably, in the described Radix Aconiti Lateralis Preparata total alkaloids, total alkaloid content is counted 127.6mg/ml with aconitine.
Further preferably, it is the medicament that is prepared from by the following weight proportion raw material:
1 part of Radix Aconiti Lateralis Preparata total alkaloids 1-2 part, Rhizoma Zingiberis extract or Rhizoma Zingiberis volatile oil.
Wherein, it is the medicament that is prepared from by the following weight proportion raw material:
2 parts of Radix Aconiti Lateralis Preparata total alkaloids, 1 part of Rhizoma Zingiberis extract.
Wherein, it is the medicament that is prepared from by the following weight proportion raw material:
1 part of Radix Aconiti Lateralis Preparata total alkaloids, 1 part of Rhizoma Zingiberis volatile oil.
Wherein, described medicament is tablet, granule, capsule, pill or oral liquid.
The present invention also provides a kind of method for preparing the pharmaceutical composition for the treatment of heart failure, comprises the steps:
A, Radix Aconiti Lateralis Preparata total alkaloids 1-5 part, Rhizoma Zingiberis effective site 1-2 part, described Rhizoma Zingiberis effective site is Rhizoma Zingiberis extract, Rhizoma Zingiberis volatile oil;
B, mixing add acceptable accessories or complementary composition and are prepared into preparation pharmaceutically commonly used.
The present invention also provides the purposes of this pharmaceutical composition in the medicine of preparation treatment heart failure.
Radix Aconiti Lateralis Preparata total alkaloids is the main toxic component of Radix Aconiti Lateralis Preparata, is again the main active component of Radix Aconiti Lateralis Preparata performance recuperating depleted YANG and rescuing the patient from collapse effect, and its toxic effect relation is close unusually.When 2: 1 compatibilities of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract, Radix Aconiti Lateralis Preparata total alkaloids and 1: 1 compatibility of Rhizoma Zingiberis volatile oil, have synergism and attenuation, drug effect is clear and definite, and toxicity is low, provides a kind of new selection for clinical.
The specific embodiment
The preparation method of embodiment 1 medicine of the present invention
Get raw material Radix Aconiti Lateralis Preparata 100g, Rhizoma Zingiberis 100g, add to 10 times of water gagings and decoct, fry in shallow oil 6h after boiling and incline and supernatant, filter, be concentrated into then and be equivalent to every milliliter and contain the 1g Radix Aconiti Lateralis Preparata, add starch and granulate, add magnesium stearate, tabletting, tablet.
The preparation of embodiment 2 medicines of the present invention
Get raw material Radix Aconiti Lateralis Preparata 500g, Rhizoma Zingiberis 200g, press the method for embodiment 1 and extract, granulate, encapsulated, get capsule.
The preparation of embodiment 3 medicines of the present invention
Get raw material Radix Aconiti Lateralis Preparata 100g, Rhizoma Zingiberis 200g, the method for medicinal material extract method or embodiment 1 is extracted routinely, granulates, and is encapsulated, gets capsule.
The preparation of embodiment 4 medicines of the present invention
Get commercially available Radix Aconiti Lateralis Preparata total alkaloids 500g, Rhizoma Zingiberis extract 100g, add starch, dextrin, granulate, encapsulated, get capsule.
The preparation of embodiment 5 medicines of the present invention
Get commercially available Radix Aconiti Lateralis Preparata total alkaloids 100g, Rhizoma Zingiberis extract 100g, add starch, dextrin, granulate, tabletting gets tablet.
The preparation of embodiment 6 medicines of the present invention
Get commercially available Radix Aconiti Lateralis Preparata total alkaloids 500g, Rhizoma Zingiberis volatile oil 200g adds starch, dextrin, granulates, and is encapsulated, gets capsule.
The preparation of embodiment 7 medicines of the present invention
Get commercially available Radix Aconiti Lateralis Preparata total alkaloids 300g, Rhizoma Zingiberis volatile oil 200g adds starch, dextrin, granulates, and is encapsulated, gets capsule.
The preparation of embodiment 8 medicines of the present invention
Get commercially available Radix Aconiti Lateralis Preparata total alkaloids 100g, Rhizoma Zingiberis volatile oil 100g adds starch, dextrin, granulates, and tabletting gets tablet.
Below prove beneficial effect of the present invention by concrete pharmacodynamics test.
Primary crude drug Radix Aconiti Lateralis Preparata Rhizoma Zingiberis compatibility test in test example 1 medicine of the present invention
One, the variation test of the maximum climbing speed of left ventricular pressure
The variation of the maximum climbing speed of table 1 heart failure rat left ventricular pressure
Annotate: compare with the blank group
* *P＜0.001; Compare with model control group
▲P＜0.05,
▲ ▲P＜0.01,
▲ ▲ ▲P＜0.001
3.5 the variation of the maximum fall off rate of Radix Aconiti Lateralis Preparata Rhizoma Zingiberis compatibility left ventricular pressure
The variation of the maximum fall off rate of table 2 heart failure rat left ventricular pressure
Annotate: compare with the blank group
* *P＜0.001; Compare with model control group
▲P＜0.05,
▲ ▲P＜0.01,
▲ ▲ ▲P＜0.001
3.6 the variation of Radix Aconiti Lateralis Preparata Rhizoma Zingiberis compatibility left ventricular pressure
The table 3 heart failure rat left side heart
The variation of pressing (X ± SD)
Annotate: compare with the blank group
* *P＜0.001; Compare with model control group
▲P＜0.05,
▲ ▲P＜0.01,
▲ ▲ ▲P＜0.001
3.7 the variation of Radix Aconiti Lateralis Preparata Rhizoma Zingiberis compatibility ventricular end diastolic pressure
The variation of table 4 heart failure rat ventricular end diastolic pressure
Annotate: compare with the blank group
* *P＜0.001; Compare with model control group
▲P＜0.05,
▲ ▲P＜0.01
3.8 the variation of Radix Aconiti Lateralis Preparata Rhizoma Zingiberis compatibility heart rate
The variation of table 5 heart failure rat heart rate
Annotate: compare with the blank group
* *P＜0.001; Compare with model control group
▲P＜0.05,
▲ ▲P＜0.01
4. experiment conclusion
The SD rat is after vena femoralis injection propafenone hydrochloride injection (16.5mg/kg) modeling, in duodenal administration Radix Aconiti Lateralis Preparata and each each one pack system of active component Radix Aconiti Lateralis Preparata Rhizoma Zingiberis of Rhizoma Zingiberis, the maximum climbing speed (dp/dtmax) of animal left ventricular pressure, the maximum fall off rate of left ventricular pressure (dp/dtmax) and heart rate (HR) in various degree rising is all arranged, wherein the Radix Aconiti Lateralis Preparata total alkali is best in the duodenal administration drug effect, next is a Radix Aconiti Lateralis Preparata polysaccharide, is the Radix Aconiti Lateralis Preparata scale once more.Rhizoma Zingiberis extract and Rhizoma Zingiberis volatile oil are very not remarkable for SD rat drug effect after vena femoralis injection propafenone hydrochloride injection (16.5mg/kg) modeling.
Above-mentioned test shows, Radix Aconiti Lateralis Preparata compatibility Rhizoma Zingiberis decoct all has improvement in various degree to the intrinsic pressure maximum rising of rat left chamber, fall off rate, wherein 1: 1,5: 2 groups with the acute heart failure model group significant difference is relatively arranged, prompting Radix Aconiti Lateralis Preparata compatibility Rhizoma Zingiberis may be by strengthening myocardial contraction, improve cardiac function thereby play, strengthen the effect of its recuperating depleted YANG and rescuing the patient from collapse; 1: 1,2: 1,5: 2 groups and the comparison of acute heart failure model group reduced the effect of feritin, angiotensin, aldosterone, atrial natriuretic peptide, Endothelin in addition in various degree.
The experiment of test example 2 Radix Aconiti Lateralis Preparata total alkaloids of the present invention and Rhizoma Zingiberis effective site compatibility Attenuation
1, the selection of Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis Attenuation component compatibility
Show from above-mentioned Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis one pack system studies on acute toxicity result: the toxic component of Radix Aconiti Lateralis Preparata is mainly Radix Aconiti Lateralis Preparata total alkaloids, and Radix Aconiti Lateralis Preparata water-soluble alkaloid, Radix Aconiti Lateralis Preparata polysaccharide, Rhizoma Zingiberis volatile oil, Rhizoma Zingiberis extract there is no overt toxicity.Therefore, when the component compatibility that carries out Attenuation is selected, mainly select the bigger Radix Aconiti Lateralis Preparata total alkaloids of toxicity, carry out attenuation research with Rhizoma Zingiberis volatile oil, Rhizoma Zingiberis extract compatibility respectively.In the selection of Attenuation component compatibility ratio, adopt Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis volatile oil, 1: 1,2: 1,1: 2,5: 2 four ratios of Rhizoma Zingiberis extract compatibility to carry out the attenuation research of component compatibility, determine the relation between Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility and Radix Aconiti Lateralis Preparata, the Rhizoma Zingiberis decoction pieces compatibility Attenuation.
2, experiment material
2.1 medicine
Radix Aconiti Lateralis Preparata total alkaloids, every ml is equivalent to crude drug in whole 1kg, and total alkaloid content is 127.6mg/ml (in an aconitine);
Rhizoma Zingiberis extract, every ml is equivalent to crude drug in whole 2g;
Rhizoma Zingiberis volatile oil, every ml is equivalent to crude drug in whole 40g.
Provide by Chemistry for Chinese Traditional Medicine teaching and research room of Chengdu University of Traditional Chinese Medicine.During experiment all be subjected to the reagent thing all to be made into every ml to be equivalent to crude drug in whole 1g standby, be made into 1: 1,1: 2,2: 1,5: 2 with the Radix Aconiti Lateralis Preparata total alkaloids median lethal dose(LD 50) and the different proportion compatibilities of Rhizoma Zingiberis extract, Rhizoma Zingiberis volatile oil the component compatibility of totally 8 ratios is standby half an hour before experiment then.
2.2 animal
Kunming mouse, male and female half and half, body weight 18～22g is provided by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center, the quality certification number: the real moving pipe 04-11 in river.The quarantine back is standby.
2.3 instrument
The PA2003 electronic balance, balance equipment factory in Shanghai produces.
3, experimental technique
Get 72 of Kunming mouses, male and female half and half, be divided into blank group (N=8), Radix Aconiti Lateralis Preparata total alkali and 1: 1 group of (N=8), 1: 2 group (N=8) of Rhizoma Zingiberis extract compatibility, 2: 1 groups (N=8), 5: 2 groups (N=8) at random, 1: 1 group of (N=8), 1: 2 group (N=8) of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility, 2: 1 groups (N=8), 5: 2 groups (N=8).Water 12hr is can't help in fasting, Radix Aconiti Lateralis Preparata total alkali Rhizoma Zingiberis extract group 1: 1 (0.25ml total alkali+0.25ml Rhizoma Zingiberis extract); Radix Aconiti Lateralis Preparata total alkali Rhizoma Zingiberis extract group 2: 1 (0.5ml total alkali+0.25ml Rhizoma Zingiberis extract); Radix Aconiti Lateralis Preparata total alkali Rhizoma Zingiberis extract group 1: 2 (0.25ml total alkali+0.50ml Rhizoma Zingiberis extract); Radix Aconiti Lateralis Preparata total alkali Rhizoma Zingiberis extract group 5: 2 (0.5ml total alkali+0.20ml Rhizoma Zingiberis extract); Radix Aconiti Lateralis Preparata total alkali Rhizoma Zingiberis volatile oil group 1: 1 (0.25ml total alkali+0.25ml Rhizoma Zingiberis volatile oil); Radix Aconiti Lateralis Preparata total alkali Rhizoma Zingiberis volatile oil group 2: 1; (0.50ml total alkali+0.25ml Rhizoma Zingiberis volatile oil); Radix Aconiti Lateralis Preparata total alkali Rhizoma Zingiberis volatile oil group 1: 2 (0.25ml total alkali+0.50ml Rhizoma Zingiberis volatile oil); Radix Aconiti Lateralis Preparata total alkali Rhizoma Zingiberis volatile oil group 5: 2 (0.50ml total alkali+0.20ml Rhizoma Zingiberis volatile oil).All are subjected to reagent thing group all to irritate stomach with the dosage of each maximum volume 0.40ml/10g.B.W, and 3 times/d, continuous 14d.The observed and recorded animal has or not death and toxic reaction
4, experimental result
The body weight of surviving animals increases gradually, mice develop is normal, by hair dense glossy and cling to the body, breathe normal, lethargy, appetite is not good enough, no abnormal secretions, the crissum cleaning, spontaneous activity reduces.Kunming mouse is after the administration first time, and Radix Aconiti Lateralis Preparata total alkali compatibility Rhizoma Zingiberis extract 1: 1 (0.25ml total alkali+0.25ml Rhizoma Zingiberis extract) in 1: 2 (0.25ml total alkali+0.5ml Rhizoma Zingiberis extract), has 2 to only reach 1 animal dead respectively; After the administration second time, Radix Aconiti Lateralis Preparata total alkali compatibility Rhizoma Zingiberis extract 1: 1 (0.25ml total alkali+0.25ml Rhizoma Zingiberis extract, i.e. median lethal dose(LD 50)) in 1: 2 (0.25ml total alkali+0.5ml Rhizoma Zingiberis extract), has 2 to only reach 1 animal dead respectively again; After administration for the third time, 5: 2 (0.50ml total alkali+0.20ml Rhizoma Zingiberis volatile oil) ratios of Radix Aconiti Lateralis Preparata total alkali compatibility Rhizoma Zingiberis volatile oil have 1 animal dead.The naked eyes animal that becomes celestial generally sees enteric cavity hyperemia, and the naked eyes heart, brain, Liver and kidney and hetero-organization thereof show no obvious abnormalities.Other ratio component compatibilities are not found animal dead.Finish the back and dissect survival mice, each main organs there is no unusually.Each is organized body weight change and sees table 6 for details.
Table 6: Radix Aconiti Lateralis Preparata Rhizoma Zingiberis component compatibility is to the influence of mice body weight and survival
Above-mentioned compatibility attenuation test explanation, at Radix Aconiti Lateralis Preparata total alkali+Rhizoma Zingiberis extract at 2: 1,1-5: 2 o'clock, all can reach and alleviate the toxic effect of Radix Aconiti Lateralis Preparata total alkali; Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil were 1: 1, (1-5): (1-2) during proportioning, all can reach and alleviate the toxic effect of Radix Aconiti Lateralis Preparata total alkali.
The selection of test example 3 Radix Aconiti Lateralis Preparata total alkaloids of the present invention and Rhizoma Zingiberis effective site potentiation component compatibility
Radix Aconiti Lateralis Preparata is mainly Radix Aconiti Lateralis Preparata total alkaloids to the active component of acute heart failure yang deficiency rat performance recuperating depleted YANG and rescuing the patient from collapse effect, and Radix Aconiti Lateralis Preparata water-soluble alkaloid, Radix Aconiti Lateralis Preparata polysaccharide, Rhizoma Zingiberis volatile oil, Rhizoma Zingiberis extract are not obvious to the recuperating depleted YANG and rescuing the patient from collapse effect of acute heart failure yang deficiency rat.When the component compatibility that carries out potentiation (recuperating depleted YANG and rescuing the patient from collapse) effect is selected, mainly select the tangible Radix Aconiti Lateralis Preparata total alkaloids of recuperating depleted YANG and rescuing the patient from collapse effect, carry out potentiation (recuperating depleted YANG and rescuing the patient from collapse) research with Rhizoma Zingiberis volatile oil, Rhizoma Zingiberis extract compatibility respectively.Adopt Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis volatile oil, 1: 1,2: 1,1: 2,5: 2 four ratios of Rhizoma Zingiberis extract compatibility to carry out potentiation (recuperating depleted YANG and rescuing the patient from collapse) the effect research of component compatibility, inquire into the relation between Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility and Radix Aconiti Lateralis Preparata, the potentiation of Rhizoma Zingiberis decoction pieces compatibility.
1, experiment material
1.1 medicine
Be subjected to the reagent thing
Radix Aconiti Lateralis Preparata total alkaloids, every ml is equivalent to crude drug in whole 1kg, and total alkaloid content is 127.6mg/ml (in an aconitine);
Rhizoma Zingiberis extract, every ml is equivalent to crude drug in whole 2g;
Rhizoma Zingiberis volatile oil, every ml is equivalent to crude drug in whole 40g.
Provide by Chemistry for Chinese Traditional Medicine teaching and research room of Chengdu University of Traditional Chinese Medicine.During experiment all be subjected to the reagent thing all to be made into every ml to be equivalent to crude drug in whole 1g standby, be equivalent to crude drug in whole 10 times amounts (2.5ml/kg) with Radix Aconiti Lateralis Preparata total alkaloids half an hour before experiment then, and the component compatibility of totally 8 ratios is standby to be made into 1: 1,1: 2,2: 1,5: 2 with Rhizoma Zingiberis extract, Rhizoma Zingiberis volatile oil respectively.
The positive control medicine
SHENFU ZHUSHEYE: Sanjiu Pharmaceutical Industry Co., Ltd., Ya'an City produces, and lot number: the accurate word Z51020664 of traditional Chinese medicines, specification: 10ml/ props up.
The modeling medicine
The propafenone hydrochloride injection: White Cloud Mountain, Guangzhou Ming Xing pharmaceutical factory produces, lot number: 030501 specification: 35mg/10ml.
1.2 laboratory animal
The healthy SD rat, male and female all have, body weight 250 ± 20g, animal production licence number: 04-11.Provide by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center, the quarantine back is standby.
1.3 experimental apparatus
Photoelectric analytical balance: Shanghai Second Balance Factory provides
BL-420 four road physiology monitors: Chengdu TME Technology Co., Ltd. provides;
LDR4-8.4 type low speed refrigerated centrifuge: Beijing Medical Centrifugal Machine Factory;
Needle electrode; Pressure transducer; The plastic three-way switch; The ventricle intubate; Bulldog clamp; Mosquito forceps; Eye scissors; Tweezers; Scalpel; Syringe; Irrigation stomach device; Electronic balance; Stopwatch; Filter paper.
1.4 experiment reagent
75% ethanol: sky, Chengdu China science service limited company produces, GB/T679-2002, and product batch number: 20060017, specification: 250ml/ bottle.
Heparin sodium: Tianjin chemical pharmaceutical factory produces, and authentication code: the accurate word of medicine is defended No. 001562 in Tianjin, specification: 6250u/ml, every 2ml.
2, experimental technique
Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the hemodynamic experimentation of acute heart failure rat
Get 66 of healthy SD rats, male and female half and half, body weight 250 ± 20g is divided into blank group (N=6) at random, model control group (N=6), join attached positive controls (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6).The acute heart failure modeling method is the same, the experimentation of the same Radix Aconiti Lateralis Preparata of medication, Rhizoma Zingiberis one pack system recuperating depleted YANG and rescuing the patient from collapse effect.
1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract by 0.5g/100g give, 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract by 0.75g/100g give, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts by 0.375g/100g give, Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract give by 0.35g/100g for 5: 2 groups; 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil by 0.5g/100g give, 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil by 0.75g/100g give, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils by 0.375g/100g give, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil give by 0.35g/100g for 5: 2 groups.(being subjected to reagent thing group dosage to be equivalent to 10 times of human crude drug amount) is in duodenal administration.The positive drug group gives SHENFU ZHUSHEYE (being equivalent to 10 times of people's consumptions) through femoral vein by 6.67ml/kg.The model drug group gives the equivalent distilled water through duodenum.
Observe 5min, 10min after the administration, 15min, 20min, 25min, 30min, 35min, 40min, 50min, 60min medicine respectively (dp/dtmax) and the influence of heart rate (HR) to the maximum climbing speed (dp/dtmax) of left ventricular pressure, the maximum fall off rate of left ventricular pressure.Parameter setting: electrocardio: 500 times of gain G, time constant T0.1S, filtering F300Hz, scanning speed 200ms/div, left ventricular pressure: 50 times of gain G, time constant TDC, filtering F30Hz, scanning speed 200ms/div, the left ventricle differential is intrinsic pressure: 100 times of gain G, time constant TDC, filtering F10Hz, scanning speed 200ms/div.The experimental data data is carried out statistical procedures with the SPSS12.0 statistical package.
3, experimental result: the Rhizoma Zingiberis component compatibility is to the hemodynamic influence of acute heart failure rat
(1) to the influence of acute heart failure yang deficiency rat heart rate
Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, each group all was improved to some extent to acute heart failure rat heart rate in each time period.Except that Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility 1: 2 group of each time period and model group relatively the no difference of science of statistics, all the other each groups more all have significant difference in different time sections and model group.Wherein, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibilities after administration 25 minutes, 30 minutes, 35 minutes, 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibilities after administration 15 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility after administration 15 minutes, 25 minutes, 30 minutes, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities after administration 10 minutes, 15 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, acute heart failure rat heart rate and Radix Aconiti Lateralis Preparata total alkali group relatively have significant difference.The result sees table 7 for details.
The influence of table 7 pair acute heart failure yang deficiency rat heart rate (X ± SD)
Annotate: compare with the blank group,
▲P＜0.05,
▲ ▲P＜0.01,
▲ ▲ ▲P＜0.001;
Compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001;
Compare with Radix Aconiti Lateralis Preparata total alkali group,
◆P＜0.05,
◆ ◆P＜0.01,
◆ ◆ ◆P＜0.001.
(2) to the influence of the maximum climbing speed of left ventricular pressure
Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, each group all has obvious rising in each time period to the maximum climbing speed of acute heart failure rat left ventricular pressure (dp/dtmax).Remove 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility after administration 50 minutes, 60 minutes, 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility after administration 40 minutes, 50 minutes, 60 minutes, 5: 2 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibilities after administration 15 minutes, 20 minutes 25 minutes, 30 minutes, 35 minutes, 40 minutes, 50 minutes, 60 minutes, 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility after administration 60 minutes, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities after administration 35 minutes, 50 minutes, 60 minutes, 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility after administration 10 minutes, 30 minutes, 35 minutes, 40 minutes, 50 minutes, 60 minutes, 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities after administration 30 minutes, 40 minutes, 50 minutes, 60 minutes with model group relatively outside the no difference of science of statistics, all the other each groups more all have significant difference in other different time sections and model group.Wherein, after administration 25 minutes, 1: 1 group, 2: 1 groups of maximum climbing speeds (dp/dtmax) of the acute heart failure rat left ventricular pressure that all can significantly raise of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility relatively had significant difference with Radix Aconiti Lateralis Preparata total alkali group.Though all the other each group is at other different time sections maximum climbing speed (dp/dtmax) of acute heart failure rat left ventricular pressure that also can raise, but reduced the effect of the maximum climbing speed of Radix Aconiti Lateralis Preparata total alkaloids rising acute heart failure rat left ventricular pressure (dp/dtmax) behind the compatibility to some extent, wherein 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility are after administration 50 minutes, 60 minutes, 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility after administration 40 minutes, 50 minutes, 60 minutes, 5: 2 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibilities after administration 5 minutes, 10 minutes, 15 minutes, 20 minutes, 40 minutes, 50 minutes, 60 minutes, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities after administration 50 minutes, 60 minutes, 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility after administration 5 minutes, 10 minutes, 40 minutes, 50 minutes, 60 minutes, 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities after administration 40 minutes, 50 minutes, 60 minutes, can obviously reduce of the effect of Radix Aconiti Lateralis Preparata total alkali, significant difference relatively be arranged with Radix Aconiti Lateralis Preparata total alkali group to the maximum climbing speed of acute heart failure rat left ventricular pressure (dp/dtmax).The result sees table 8 for details.
The influence of table 8 couple acute heart failure yang deficiency rat dp/dtmax (X ± SD)
Annotate: compare with the blank group,
▲P＜0.05,
▲ ▲P＜0.01,
▲ ▲ ▲P＜0.001;
Compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001;
Compare with Radix Aconiti Lateralis Preparata total alkali group,
◆P＜0.05,
◆ ◆P＜0.01,
◆ ◆ ◆P＜0.001.
(3), to the influence of the maximum fall off rate of left ventricular pressure
Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, each group (dp/dtmax) all has obvious rising in each time period to the maximum fall off rate of acute heart failure rat left ventricular pressure.Remove 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility after administration 40 minutes, 50 minutes, 60 minutes, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibilities, 1: 2 group after administration 35 minutes, 40 minutes, 50 minutes, 60 minutes, 5: 2 groups of each time periods after administration of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility, 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility after administration 60 minutes, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities after administration 50 minutes, 60 minutes, 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility after administration 10 minutes, 15 minutes, 20 minutes, 30 minutes, 35 minutes, 40 minutes, 50 minutes, 60 minutes, 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities after administration 40 minutes, 50 minutes, 60 minutes with model group relatively outside the no difference of science of statistics, all the other each groups more all have significant difference in other different time sections and model group.Wherein, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibilities after administration 25 minutes, 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility 5 minutes, 25 minutes maximum fall off rates of the acute heart failure rat left ventricular pressure that all can significantly raise after administration (dp/dtmax), relatively have significant difference with Radix Aconiti Lateralis Preparata total alkali group.Though all the other each groups also can raise the maximum fall off rate of acute heart failure rat left ventricular pressure (dp/dtmax) in other different time sections, but reduced maximum fall off rate (effect dp/dtmax) of Radix Aconiti Lateralis Preparata total alkaloids rising acute heart failure rat left ventricular pressure behind the compatibility to some extent, wherein 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility are after administration 40 minutes, 50 minutes, 60 minutes, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibilities after administration 40 minutes, 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract compatibility, 5: 2 groups after administration 40 minutes, 50 minutes, 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities after administration 50 minutes, 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility after administration 40 minutes, 50 minutes, 60 minutes, (effect dp/dtmax) relatively has significant difference with Radix Aconiti Lateralis Preparata total alkali group to the maximum fall off rate of acute heart failure rat left ventricular pressure obviously to reduce the Radix Aconiti Lateralis Preparata total alkali.The result sees table 9 for details.
The influence of table 9 couple acute heart failure yang deficiency rat-dp/dtmax
Annotate: compare with the blank group,
▲P＜0.05,
▲ ▲P＜0.01,
▲ ▲ ▲P＜0.001;
Compare with model group,
*P＜0.05,
*P＜0.01,
* *P＜0.001;
Compare with Radix Aconiti Lateralis Preparata total alkali group,
◆P＜0.05,
◆ ◆P＜0.01,
◆ ◆ ◆P＜0.001.
Above-mentioned evidence, Radix Aconiti Lateralis Preparata total alkaloids are the main toxic component of Radix Aconiti Lateralis Preparata, are again the main active components of Radix Aconiti Lateralis Preparata performance recuperating depleted YANG and rescuing the patient from collapse effect, and its toxic effect relation is close unusually.In conjunction with the conclusion of test example 1 as can be known, when 2: 1 compatibilities of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract, Radix Aconiti Lateralis Preparata total alkaloids and 1: 1 compatibility of Rhizoma Zingiberis volatile oil, has synergism and attenuation; When 5: 2 compatibilities of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract, Radix Aconiti Lateralis Preparata total alkaloids and 1: 2,2: 1,5: 2 compatibilities of Rhizoma Zingiberis volatile oil, have attenuation and subtract the effect effect; During 1: 1 compatibility of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract, have and increase malicious potentiation; During 1: 2 compatibility of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract, have the poison of increasing and subtract the effect effect.
At above-mentioned test, medicine of the present invention is carried out Study on mechanism, test as follows:
Test example 4 Radix Aconiti Lateralis Preparata total alkaloids of the present invention and Rhizoma Zingiberis effective site compatibility strengthen the experiment of recuperating depleted YANG and rescuing the patient from collapse mechanism of action
1 experiment material
1.1 medicine
Be subjected to the reagent thing
Radix Aconiti Lateralis Preparata total alkaloids, every ml is equivalent to crude drug in whole 1kg, and total alkaloid content is 127.6mg/ml (in an aconitine);
Rhizoma Zingiberis extract, every ml is equivalent to crude drug in whole 2g;
Rhizoma Zingiberis volatile oil, every ml is equivalent to crude drug in whole 40g.
Provide by Chemistry for Chinese Traditional Medicine teaching and research room of Chengdu University of Traditional Chinese Medicine.During experiment all be subjected to the reagent thing all to be made into every ml to be equivalent to crude drug in whole 1g standby, be equivalent to crude drug in whole 10 times amounts (2.5ml/kg) with Radix Aconiti Lateralis Preparata total alkaloids half an hour before experiment then, and the component compatibility of totally 8 ratios is standby to be made into 1: 1,1: 2,2: 1,5: 2 with Rhizoma Zingiberis extract, Rhizoma Zingiberis volatile oil respectively.
The positive control medicine
SHENFU ZHUSHEYE: Sanjiu Pharmaceutical Industry Co., Ltd., Ya'an City produces, and lot number: the accurate word Z51020664 of traditional Chinese medicines, specification: 10ml/ props up.
The modeling medicine
The propafenone hydrochloride injection: White Cloud Mountain, Guangzhou Ming Xing pharmaceutical factory produces, lot number: 030501 specification: 35mg/10ml.
1.2 laboratory animal
The healthy SD rat, male and female all have, body weight 250 ± 20g, animal production licence number: 04-11.Provide by Chengdu University of Traditional Chinese Medicine Animal Experimental Study center, the quarantine back is standby.
1.3 experimental apparatus
Photoelectric analytical balance: Shanghai Second Balance Factory provides
BL-420 four road physiology monitors: Chengdu TME Technology Co., Ltd. provides;
LDR4-8.4 type low speed refrigerated centrifuge: Beijing Medical Centrifugal Machine Factory
Needle electrode; Pressure transducer; The plastic three-way switch; The ventricle intubate; Bulldog clamp; Mosquito forceps; Eye scissors; Tweezers; Scalpel; Syringe; Irrigation stomach device; Electronic balance; Stopwatch; Filter paper.
1.4 experiment reagent
75% ethanol: sky, Chengdu China science service limited company produces, GB/T679-2002, and product batch number: 20060017, specification: 250ml/ bottle.
Heparin sodium: Tianjin chemical pharmaceutical factory produces, and authentication code: the accurate word of medicine is defended No. 001562 in Tianjin, specification: 6250u/ml, every 2ml;
Angiotensin I radioimmunology analysis medicine box: provided lot number by the Beijing North biotechnology research: 20060820.
Angiotensin II radioimmunology analysis medicine box: provided lot number by the Beijing North biotechnology research: 20060820.
Aldosterone radioimmunology analysis medicine box: provided lot number by the Beijing North biotechnology research: 20050401.
Atrial natriuretic peptide radioimmunology analysis medicine box: provided lot number by the Beijing North biotechnology research: 20051201.
Endothelin radioimmunology analysis medicine box: provided lot number by the Beijing North biotechnology research: 20051201.
Tumor necrosis factor radioimmunology analysis medicine box: provided lot number by the Beijing North biotechnology research: 20040601A.
2 experimental techniques
2.1 Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the experimentation of acute heart failure rat renin angiotensin-aldosterone system (RAAS)
Get 66 of healthy SD rats, male and female half and half, body weight 250 ± 20g is divided into blank group (N=6) at random, model control group (N=6), join attached positive controls (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6).The acute heart failure modeling method is the same, and medication, the same Radix Aconiti Lateralis Preparata of dosage, Rhizoma Zingiberis component compatibility are to the hemodynamics experimentation of acute heart failure rat.
Each treated animal was all got blood in femoral artery in 60 minutes after administration, separated plasma is measured plasma angiotensinogen I, the content of Angiotensin II, aldosterone.Each organize data with
Represent the t check between organizing with the SPSS12.0 statistical package.
(1) mensuration of angiotensin I (AI), Angiotensin II (AII): femoral artery is got blood 2ml, be injected into immediately in the enzyme inhibitor anticoagulant tube of pre-cooling (containing EDTA 20ul, dimercaptopropanol, BAL 10ul, Hydroxyquinoline Sulfate 20ul), turn upside down after the mouth of pipe sealed for several times, at once put into the ice-water bath kind behind the mixing 1 hour, take out back 2500r/ branch, centrifugal 7 minutes, separated plasma ,-20 ℃ of preservations are to be measured.Before the mensuration, place room temperature to place 15 minutes in sample, the 3500r/ branch, centrifugal 15 minutes, inhale and abandon supernatant, survey the radiocounting (detecting) of a precipitation tube by analyzing the box explanation.
(2) mensuration of aldosterone: femoral artery is got blood 1ml, is injected into contain (the heparin sodium 0.1mg/ml blood) in the heparin sodium centrifuge tube of pre-cooling immediately, shake up, and at 2000r/min centrifugal 5 minutes, separated plasma ,-20 ℃ of preservations are to be measured.Before the mensuration, place room temperature to place 15 minutes in sample, the 3500r/ branch, centrifugal 15 minutes, inhale and abandon supernatant, survey the radiocounting (detecting) of a precipitation tube by analyzing the box explanation.
2.2 Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the experimentation of acute heart failure rat atrial natriuretic peptide
Get 66 of healthy SD rats, male and female half and half, body weight 250 ± 20g is divided into blank group (N=6) at random, model control group (N=6), join attached positive controls (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6).The acute heart failure modeling method is the same, and medication, the same Radix Aconiti Lateralis Preparata of dosage, Rhizoma Zingiberis component compatibility are to the hemodynamics experimentation of acute heart failure rat.
Each treated animal was all got blood in femoral artery in 60 minutes after administration, separated plasma is measured the content of Plasma Atrial Natriuretic Peptide.Each organize data with
Represent the t check between organizing with the SPSS12.0 statistical package.
The mensuration of atrial natriuretic peptide (ANP): femoral artery is got blood 1ml, is injected into ready getting in the blood vessel immediately and (contains EDTA 20ul, aprotinin 10ul), turns upside down after the mouth of pipe is sealed for several times, 2000r/ branch behind the mixing, centrifugal 5 minutes, separated plasma ,-20 ℃ of preservations are to be measured.Before the mensuration, place room temperature to place 15 minutes in sample, the 3500r/ branch, centrifugal 15 minutes, inhale and abandon supernatant, survey the radiocounting (detecting) of a precipitation tube by analyzing the box explanation.
2.3 Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the experimentation of acute heart failure rat Endothelin
Get 66 of healthy SD rats, male and female half and half, body weight 250 ± 20g is divided into blank group (N=6) at random, model control group (N=6), join attached positive controls (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6).The acute heart failure modeling method is the same, and medication, the same Radix Aconiti Lateralis Preparata of dosage, Rhizoma Zingiberis component compatibility are to the hemodynamics experimentation of acute heart failure rat.
Each treated animal was all got blood in femoral artery in 60 minutes after administration, separated plasma is measured the content of endothelin level.Each organize data with
Represent the t check between organizing with the SPSS12.0 statistical package.
The mensuration of Endothelin (ET): femoral artery is got blood 1ml, is injected into ready getting in the blood vessel immediately and (contains EDTA 15ul), turns upside down after the mouth of pipe is sealed for several times, mixing, room temperature were placed after 1 hour, the 3000r/ branch, centrifugal 10 minutes, separated plasma ,-20 ℃ of preservations are to be measured.Before the mensuration, place room temperature to place 15 minutes in sample, the 3500r/ branch, centrifugal 15 minutes, inhale and abandon supernatant, survey the radiocounting (detecting) of a precipitation tube by analyzing the box explanation.
2.4 Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the experimentation of acute heart failure rat tumor necrosin
Get 66 of healthy SD rats, male and female half and half, body weight 250 ± 20g is divided into blank group (N=6) at random, model control group (N=6), join attached positive controls (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extracts (N=6), 1: 1 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 1: 2 group of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil (N=6), 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6), 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oils (N=6).The acute heart failure modeling method is the same, and medication, the same Radix Aconiti Lateralis Preparata of dosage, Rhizoma Zingiberis component compatibility are to the hemodynamics experimentation of acute heart failure rat.
Each treated animal was all got blood in femoral artery in 60 minutes after administration, separated plasma is measured the content of blood plasma tumor necrosis factor.Each organize data with
Represent the t check between organizing with the SPSS12.0 statistical package.
The mensuration of tumor necrosis factor (TNF): femoral artery is got blood 2ml, is injected into ready getting in the blood vessel immediately and (contains EDTA 6ul), and mixing is immediately at the 2000r/ branch, centrifugal 5 minutes, separated plasma was got 0.8ml blood plasma immediately, add the 8ul aprotinin, shake up ,-20 ℃ of conditions are preserved to be measured.Before the mensuration, place room temperature to place 15 minutes in sample, the 3500r/ branch, centrifugal 15 minutes, inhale and abandon supernatant, survey the radiocounting (detecting) of a precipitation tube by analyzing the box explanation.
3, experimental result
3.1 Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the influence of acute heart failure rat renin angiotensin-aldosterone system
(1) variation of angiotensin I (AI) content
After the model group rat gave propafenone hydrochloride (16.5mg/kg) modeling, angiotensin I (AI) level significantly raise, and with the blank group significant difference is arranged relatively.Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, except that positive controls, Radix Aconiti Lateralis Preparata total alkali and 1: 1,2: 1 groups of rising angiotensin Is of Rhizoma Zingiberis extract, all the other each groups all can reduce the level of acute heart failure rat serum angiotensin I (AI), wherein reduce comparatively star for 1: 2 group with Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract especially, but compare difference that there are no significant with model group.The result sees table 10 for details.
The influence of table 10 couple acute heart failure yang deficiency rat AI
Annotate: compare with the blank group,
*P＜0.05,
*P＜0.01.
(2), the variation of Angiotensin II (AII) content
Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, removed Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility 1: 2,5: 2, Radix Aconiti Lateralis Preparata total alkali and 1: 2 pair of acute heart failure rat serum of Rhizoma Zingiberis volatile oil compatibility angiotensin II (AII) have outside the reduction effect, and all the other each group all has to a certain degree rising to acute heart failure rat serum angiotensin II (AII).Wherein 2: 1 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibilities, Radix Aconiti Lateralis Preparata total alkali and 1: 1 group of acute heart failure rat serum angiotensin II (AII) level that can obviously raise of Rhizoma Zingiberis volatile oil compatibility are learned by statistics and are handled, and its result has significant difference.The result sees table 11 for details.
The influence of table 11 couple acute heart failure yang deficiency rat AII
Annotate: compare with the blank group,
*P＜0.05; Compare with model group,
◆P＜0.05,
◆ ◆P＜0.01.
(3), the variation of aldosterone (Ald.) content
Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, positive controls, Radix Aconiti Lateralis Preparata total alkali and 1: 1,2: 1,1: 2 group of Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility all can reduce acute heart failure rat plasma aldosterone (Ald.) level for 2: 1,5: 2 groups, but compare difference that there are no significant with model group.All the other each groups have certain rising effect to acute heart failure rat plasma aldosterone (Ald.) level, and credit is analysed by statistics, also there was no significant difference.The result sees table 12 for details.
The influence of table 12 couple acute heart failure yang deficiency rat Ald.
Annotate: compare with the blank group,
*P＜0.05; Compare with model group,
◆P＜0.05.
3.2 Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the influence of acute heart failure rat atrial natriuretic peptide
Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, except that 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities, all the other each groups all can reduce acute heart failure rat plasma atrial natriuretic peptide (ANP) level, through comparing with model group, except that Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility have the significant difference for 2: 1 groups, all the other respectively organize difference does not have significance.The result sees table 13 for details.
The influence of table 13 couple acute heart failure yang deficiency rat ANP
Annotate: compare with the blank group,
*P＜0.05; Compare with model group,
◆P＜0.05.
3.3 Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the influence of acute heart failure rat Endothelin
Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, except that 5: 2 groups of Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibilities have the rising effect (no difference of science of statistics) acute heart failure rat plasma Endothelin (ET) level, all the other each groups all can reduce acute heart failure rat plasma Endothelin (ET) level, through comparing difference that there are no significant with model group.The result sees table 14 for details.
The influence of table 14 couple acute heart failure yang deficiency rat ET
Annotate: compare with the blank group,
*P＜0.05; Compare with model group,
◆P＜0.05.
3.4 Radix Aconiti Lateralis Preparata, Rhizoma Zingiberis component compatibility are to the influence of acute heart failure rat tumor necrosin
Give SHENFU ZHUSHEYE and Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis extract compatibility, Radix Aconiti Lateralis Preparata total alkali and Rhizoma Zingiberis volatile oil compatibility respectively after 1: 1,2: 1,1: 2,5: 2, each group all can reduce acute heart failure rat plasma tumor necrosis factor (TNF) level to some extent, through comparing with model group, there are no significant for difference.The result sees table 15 for details.
The influence of table 15 couple acute heart failure yang deficiency rat TNF
Annotate: compare with the blank group,
*P＜0.05; Compare with model group,
◆P＜0.05.
Above-mentioned evidence, the mechanism of Radix Aconiti Lateralis Preparata total alkaloids and Rhizoma Zingiberis extract, Rhizoma Zingiberis volatile oil compatibility performance recuperating depleted YANG and rescuing the patient from collapse effect may can reduce acute heart failure rat plasma ANP, ET, TNF level with it, and RAAS is relevant in regulation and control.
Claims (4)
1. pharmaceutical composition for the treatment of heart failure, it is characterized in that: it is the medicament that is prepared by following step by Radix Aconiti Lateralis Preparata total alkaloids, Rhizoma Zingiberis extract:
A, with Radix Aconiti Lateralis Preparata total alkaloids, every ml is equivalent to crude drug in whole 1kg, total alkaloid content is counted 127.6mg/ml with aconitine; Rhizoma Zingiberis extract, every ml is equivalent to crude drug in whole 2g, and general gingerol content is in capsaicin 15%w/w;
B, the described Radix Aconiti Lateralis Preparata total alkaloids of a step, Rhizoma Zingiberis extract joined be prepared into every ml to be equivalent to crude drug in whole 1g standby;
C, be 2: 1, be prepared into medicament Radix Aconiti Lateralis Preparata total alkaloids, the Rhizoma Zingiberis extract proportion compatibility of b step.
2. the pharmaceutical composition of treatment heart failure according to claim 1 is characterized in that: described medicament is tablet, granule, capsule, pill or oral liquid.
3. a method for preparing the pharmaceutical composition of the described treatment heart failure of claim 1 comprises the steps:
A, with Radix Aconiti Lateralis Preparata total alkaloids, every ml is equivalent to crude drug in whole 1kg, total alkaloid content is counted 127.6mg/ml with aconitine; Rhizoma Zingiberis extract, every ml is equivalent to crude drug in whole 2g, and general gingerol content is in capsaicin 15%w/w;
B, the described Radix Aconiti Lateralis Preparata total alkaloids of a step, Rhizoma Zingiberis extract joined be prepared into every ml to be equivalent to crude drug in whole 1g standby;
C, be 2: 1, be prepared into medicament Radix Aconiti Lateralis Preparata total alkaloids, the Rhizoma Zingiberis extract proportion compatibility of b step.
4. the purposes of the described pharmaceutical composition of claim 1 in the medicine of preparation treatment heart failure.
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| CN2010102969717A CN101940778B (en) | 2006-11-23 | 2007-11-23 | Medicinal composition for treating heart failure and preparation method and application thereof |
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