CN103505451A - Traditional Chinese medicine composition for treating cardiovascular diseases and preparation method thereof - Google Patents

Traditional Chinese medicine composition for treating cardiovascular diseases and preparation method thereof Download PDF

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Publication number
CN103505451A
CN103505451A CN201210217297.8A CN201210217297A CN103505451A CN 103505451 A CN103505451 A CN 103505451A CN 201210217297 A CN201210217297 A CN 201210217297A CN 103505451 A CN103505451 A CN 103505451A
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ethanol
chinese medicine
time
medicine composition
isorhamnetin
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崔卜东
贾林
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Tianjin Tiens Biological Development Co Ltd
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Tianjin Tiens Biological Development Co Ltd
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Abstract

The invention discloses a traditional Chinese medicine composition for treating cardiovascular diseases. The traditional Chinese medicine composition comprises 20-80 percent by weight of isorhamnetin and 20-80 percent by weight of quercetin. The invention also discloses a preparation method of the traditional Chinese medicine composition. The preparation method comprises the following steps: extracting total flavones of hippophae, separating the isorhamnetin and the quercetin, and preparing the finished product according to a formula. The traditional Chinese medicine composition disclosed by the invention has high purity and low dose. Compared with a conventional hippophae total flavone extractive preparation, the traditional Chinese medicine composition has a better curative effect and is more controllable in quality and suitable for industrial production.

Description

A kind of Chinese medicine composition of Cardiovarscular and preparation method
Technical field
The Chinese medicine composition and the preparation method that the present invention relates to a kind of Cardiovarscular, belong to the field of Chinese medicines.
Background technology
Along with improving constantly of people's living standard, the change of dietary structure, aged tendency of population becomes clear day by day, and the sickness rate of coronary heart disease is day by day soaring.Coronary heart disease is because coronary atherosclerosis causes luminal stenosis, causes blood supply of cardiac muscle oxygen supply obstacle and the heart disease that causes, and " world killer " is known as.With regard to the whole world, since half a century, coronary heart disease has become the underlying cause of death of one of the disease that threat human health the is the most serious ,Shi U.S. and some industrialized country.According to World Health Organization's statistics, in the total death toll of the U.S., have 24.7% to die from coronary heart disease, Northern Ireland coronary heart disease case fatality rate occupies first place in the world, and is 5,36/,100,000; Japan is minimum, is 41,/10 ten thousand.In recent years, the M & M of China's coronary heart disease continues soaring, has every year at present 700,000 people of surpassing to die from coronary heart disease, is the modal a kind of cardiovascular diseases of middle-aged and elderly people, has leapt to as first of internal disease.Visible coronary heart disease has become global public hazards, and American wins cardiopathia for " pestilence in epoch ".
The drug main for the treatment of in the market coronary heart disease will be divided into: nitrate esters medicine (as isosorbide mononitrate soft gelatin capsule), thromboembolism preventing (coagulating) medicine (as aspirin), beta-blocker (as metoprolol), angiotensin converting enzyme inhibitor (as enalapril), calcium ion antagonist (as verapamil), fat regulation medicine (as simvastatin), anticoagulation (as heparin), the eight large classes such as Thrombolytic Drugs (as recombinant glucokinase).Because coronary heart disease is chronic disease, Drug therapy is long the course for the treatment of, and long-term taking medicine can cause the serious untoward reaction such as headache, cough, stimulation gastric mucosa, hypotension, inhibition cardiac function, infringement hepatic and renal function.So, provide controlled, cheap, the eutherapeutic pure natural plant of a kind of safety to extract medicine, there is great social meaning and economic worth.
Fructus Hippophae (HippophaerhamnoidesL.) is shrub or the dungarunga of Elaeangnaceae (Hlaeagnaceae) Hippophae, and Fructus Hippophae not only flavones content is abundant, but also contains other abundant bioactive substance.Fructus Hippophae total flavones is the important active component of Oleum Hippophae and Fructrs Hippophae seed oil.Fructus Hippophae total flavones has booster action to cardiac function, can make cardiac contractility ability strengthen, and Diastolic function improves, and the myocardial ischemia that lobus posterior hypophyseos is caused has obvious antagonism.The area of the myocardial infarction that coronary occlusion causes is obviously dwindled, also can improve the hypoxia-bearing capability under normal pressure and low pressure.Especially angina pectoris and cardiac function are improved, the cholesterol in blood, triglyceride are had to obvious reducing effect.
If current commercially available Fructus Hippophae total flavones is used for the treatment of the drug main Flavonihippophae of coronary heart disease.Xindakang capsule (sheet) contains take isorhamnetin, Quercetin, kaempferol etc. as main Fructus Hippophae total flavones.Because composition is more, there are problems in quality control aspect.The medicine that does not also have Fructus Hippophae total flavones monomer component or monomer composition to be prepared in the market.
Summary of the invention
The object of this invention is to provide a kind of good effect, the more controlled Chinese medicine composition of quality.
Another object of the present invention is to provide a kind of preparation method of described Chinese medicine composition.
Another object of the present invention is to provide a kind ofly has the Chinese medicine composition of the market competitiveness in price equally.Described Chinese medicine composition can not increase because of the raising of curative effect patient's financial burden.
For achieving the above object, the present invention by the following technical solutions:
Chinese medicine composition of the present invention is to extract highly purified Fructus Hippophae total flavones, then purifies and separates isorhamnetin and Quercetin, then according to formula ratio, isorhamnetin and Quercetin are combined.
In Chinese medicine composition of the present invention, main effective ingredient is isorhamnetin and Quercetin.
In Chinese medicine composition of the present invention, comprise the component of following percentage by weight:
Contain 20~80% isorhamnetins and 20~80% Quercetins.
In Chinese medicine composition of the present invention, preferably comprise the component of following percentage by weight:
Contain 30~70% isorhamnetins and 30~70% Quercetins.
In Chinese medicine composition of the present invention, the preferred component that comprises following percentage by weight:
Contain 40~60% isorhamnetins and 40~60% Quercetins.
In Chinese medicine composition of the present invention, further preferably comprise the component of following percentage by weight:
Contain 60% isorhamnetin and 40% Quercetin.
Chinese medicine composition of the present invention can adopt following method preparation:
(1) get Fructus Hippophae medical material, after being pulverized, add ethyl acetate and ethanol, heating and refluxing extraction, obtain extracting solution I, medicinal residues add ethanol, and heating and refluxing extraction obtains extracting solution II, merge extractive liquid, I and II, be condensed into extractum, use dissolve with ethanol extractum, adopt nonpolar or low pole macroporous resin to carry out separation to it, first with water elution, obtain eluent I; Then with ethanol elution 2 times, the volumetric concentration of eluting ethanol is 50%~60% for the first time, and the volumetric concentration of eluting ethanol is 90%~95% for the second time, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, obtain Fructus Hippophae total flavones extract;
(2) isorhamnetin and Quercetin is separated;
(3) take isorhamnetin and Quercetin, add adjuvant, be prepared into various dosage forms.
Preferably, the volume ratio of described ethyl acetate and ethanol is 1:2.
Preferably, the volumetric concentration of eluting ethanol is 60% for the first time; The volumetric concentration of eluting ethanol is 90% for the second time.
Preferred, the preparation method of Chinese medicine composition of the present invention comprises the following steps:
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 1~3 hour for the first time, 1~2 hour for the second time, filtrate merged to obtain extracting solution I, and medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 0.5~1.5 hour for the first time, 0.5~1 hour for the second time, filtrate merged to obtain extracting solution II, merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopt nonpolar or low pole macroporous resin to carry out separation to it, first with water elution, obtain eluent I; Then with 50%~60% ethanol elution, then with 90%~95% ethanol elution, obtain eluent II, reclaim, concentrating under reduced pressure, dry, obtain Fructus Hippophae total flavones extract;
(2) isorhamnetin and Quercetin is separated;
(3) take isorhamnetin and Quercetin, add adjuvant, be prepared into various dosage forms.
The described elution flow rate of step (1) is 1~4BV/h; Preferably, elution flow rate is 1~2BV/h, is more preferably 2BV/h.
Described macroporous resin is preferably AB-8 and X-5, more preferably X-5.
After testing, Fructus Hippophae total flavones product purity can reach 24~26%.
Concentration of alcohol described in the present invention is volumetric concentration.
The separation method of the isorhamnetin described in step (2) and Quercetin referring to " extraction of isorhamnetin and Quercetin and forestry institute, separated 》, Shaanxi journal 2009 in sea-buckthorn pomace, 24(5).
Dosage form described in step (3) can be the various dosage forms that on Chinese medicine composition of the present invention and any or more than one pharmaceuticss, adjuvant is mixed as starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, xylitol, lactose, glucose, glycine, mannitol, glycine etc., for example, can be made into aqueous injection, tablet, slow releasing tablet, drop pill, granule, injectable powder, capsule, microgranule.Preferred dosage form is drop pill, injectable powder.
Chinese medicine composition of the present invention can also adopt following method to realize:
Extract Fructus Hippophae total flavones, separated other compositions of removing, are controlled at the content of isorhamnetin and Quercetin in scope of the present invention.
The product that adopts said method to obtain, falls within the scope of protection of the present invention equally.
Chinese medicine composition purity of the present invention is high, dosage is little, and more traditional Fructus Hippophae total flavones extract formulation has better curative effect, and quality is more controlled, can reduce patient suffering and financial burden.
test example
(1) experimentation of medicine of the present invention and Flavonihippophae function of resisting myocardial ischemia
1, grouping and administration
60 of Wister male rats, body weight 251 ± 21g, is divided into 3 groups at random by body weight: normal saline matched group; The extract group of embodiment 2; Flavonihippophae group.Each medicine all with normal saline dilution to desired concn, dosage is 4ml/kg, tail intravenously administrable.
2, method
(1) rat experiment myocardial infarction model: animal pentobarbital sodium intraperitoneal injection of anesthesia (45mg/kg), face upward position and fix.Tracheal intubation, makes the longitudinal incision of 2cm in breastbone left side, nearly breastbone side is cut off the 3rd, the 4th and strangled cartilage, opens behind thoracic cavity, connects artificial respirator (ventilation 2ml/100g, 50 times/min).Cut off pericardium, expose heart, left anterior descending coronary artery root threading is in order to ligation, and record standard II lead electrocardiogram, stablizes 10 minutes, and following coronary artery occlusion left anterior descending branch, closes thoracic cavity.By syringe sucking-off animal throat portion secretion, make animal recover autonomous respiration.After following coronary artery occlusion 15min, intravenously administrable.After following coronary artery occlusion 4 hours, win heart, 5 of the following crosscuts of ligature, carry out NBT (NBT) dyeing, calculating myocardium Infarct area accounts for the percentage ratio of ventricle and heart area, and carries out statistical procedures (t check).
(2) in vitro langendorff heart perfusion: carry out with reference to the pharmacological experimental methodology third edition.
3, result
(1) impact on rat experiment myocardial inyaretion scope, the results are shown in Table 1.
The various extracts of table 1 on the impact of rat experiment myocardial inyaretion scope (
Figure 2012102172978100002DEST_PATH_IMAGE001
)
Group Dosage (mg/kg) Number of animals Infarcted region/ventricle (%) Infarcted region/heart (%)
The Chinese medicine composition of embodiment bis- 20 20 17.31±5.84** # 14.58±4.11** #
Flavonihippophae 20 20 24.19±7.21* 20.67±4.05*
Model group ? 20 35.03±6.65 26.13±5.42
Note: compare * P<0.05, * * P<0.01 with model group; Compare with Flavonihippophae group,<sup TranNum="133">#</sup>p<0.05,<sup TranNum="134">##</sup>p<0.01;
(2) impact on the dirty coronary flow of guinea-pig heart and heart rate, the results are shown in Table 2.
The various extracts of table 2 on the impact of rat heart coronary flow and heart rate (
Figure 607403DEST_PATH_IMAGE001
)
Group Dosage (mg/ml) Coronary flow value added (ml/min) Heart rate attenuating value (inferior/min)
The Chinese medicine composition of embodiment bis- 20 11.47±1.33 ?## 20±11 #
Flavonihippophae group 20 8.16±1.21 11±5
Note: compare with Flavonihippophae group,<sup TranNum="165">#</sup>p<0.05,<sup TranNum="166">##</sup>p<0.01.
The result demonstration of above table 1 and table 2, medicine of the present invention and Flavonihippophae all have obvious function of resisting myocardial ischemia, and the curative effect of the present composition is better than Flavonihippophae.
(2) the clinical experiment effect for the treatment of coronary heart disease
1, experimental drug
It is product, isosorbide mononitrate, simvastatin, the Flavonihippophae of the embodiment of the present invention 2 preparations that the present invention treats 1 group.
2, object choice
Select altogether out-patient's 200 examples, be divided at random treatment group of the present invention, isosorbide mononitrate group, Flavonihippophae group, four groups of simvastatin group.
Every group of 50 examples.
Treatment group 50 examples of the present invention, male 29 examples, female's 21 examples; The oldest 77 years old, minimum 50 years old, average 68.5 years old; The shortest 5 weeks of the course of disease, the longest 19 years.
Isosorbide mononitrate group 50 examples, male 25 examples, female's 25 examples; The oldest 75 years old, minimum 50 years old, average 68.4 years old; The course of disease is the shortest 4 weeks, the longest 21 years.
Flavonihippophae group 50 examples, male 24 examples, female's 26 examples; The oldest 75 years old, minimum 50 years old, average 68.6 years old; The course of disease is the shortest 3 weeks, the longest 19 years.
Simvastatin group 50 examples, male 24 examples, female's 26 examples; The oldest 76 years old, minimum 50 years old, average 67.3 years old; The course of disease is the shortest 5 weeks, the longest 20 years.
Four groups of patients carry out harmony relatively at aspects such as sex, age, the course of disease, state of an illness weight and primary diseases, and no significant difference (P > 0.05), there is comparability.
3, method
Each organizes and is 3 months the course for the treatment of; Each group is all carried out detecting ECG before treatment and after treating 3 months, implements angina pectoris symptom efficacy evaluation simultaneously.Angina pectoris attacks situation, the electrocardiogram of observing all Treatment in Patients with Coronary Hearts front and back improve situation.Conventional therapy: medicine 10mg of the present invention, every day 2 times; Oral Shu Bilaite (isosorbide mononitrate soft gelatin capsule) 10mg, every day 2 times; Oral Flavonihippophae 10mg, every day 2 times; Simvastatin 20mg, 1 time every night.Complicated hypertension person gives Treatment of Hypertension simultaneously.
4, curative effect determinate standard
With reference to national Angina Pectoris from Coronary Artery Disease with Therapy of Combination of TCM with Western Medicine forum in 1979 " angina pectoris and ECG curative effect evaluation criteria ".
(1) angina pectoris symptom efficacy evaluation: effective: equal tired degree does not cause that angina pectoris or angina pectoris attacks number of times reduce more than 80%; Effective: angina pectoris attacks number of times reduces 50%~80%; Invalid: angina pectoris attacks number of times reduces less than 50%.
(2) coronary heart disease ECG curative effect evaluation: effective: electrocardiogram returns to normally; Effective: ST section reduces, after treatment, go up more than 0.05 mV, but do not reach normal level, the negative T wave that mainly leads shoals (reaching more than 25%) or T ripple becomes upright person from smooth, or chamber or intraventricular block improver; Invalid: electrocardiogram is front basic identical with treatment.
5 results
(1) respectively organize the comparison of angina pectoris symptom curative effect
After treatment, each organizes angina pectoris situation in Table 3.The curative effect for the treatment of group of the present invention is obviously better than other each groups.Through check, the total effective rate for the treatment of group of the present invention is significantly higher than other groups (P < 0.05).
(2) respectively organize the comparison of patient's ECG curative effect
Electrocardiogram improvement situation is relatively in Table 4.As can be seen from Table 4, the total effective rate for the treatment of group of the present invention is significantly better than other groups (P < 0.05).
The comparison of table 3 angina pectoris treatment situation
Group Number of cases Effective Effectively Invalid Effective percentage (%)
Treatment group of the present invention 50 26 18 6 88.0
Isosorbide mononitrate group 50 21 17 12 76.0
Flavonihippophae group 50 21 19 10 80.0
Simvastatin group 50 20 19 11 78.0
Table 4 electrocardiogram improves situation comparison
Group Number of cases Effective Effectively Invalid Effective percentage (%)
Treatment group of the present invention 50 28 15 7 86.0
Isosorbide mononitrate group 50 23 16 11 78.0
Flavonihippophae group 50 22 19 9 82.0
Simvastatin group 50 21 19 10 80.0
As can be known from the above table, each organize medicine all have treatment anginal effect, treatment group better efficacy of the present invention.
The specific embodiment
embodiment 1
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with methanol extractum, adopts macroporous resin AB-8 to carry out separation, first with water elution, obtains eluent I; Then with 55% ethanol elution, then with 90% ethanol elution, eluent flow rate is 2.5BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.87%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 8g and the Quercetin 2g after separation, add adjuvant, be prepared into drop pill.
embodiment 2
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with methanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 60% ethanol elution, then with 95% ethanol elution, eluent flow rate is 2BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 26.53%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 6g and the Quercetin 4g after separation, add adjuvant, be prepared into drop pill.
embodiment 3
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 2 hours for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 55% ethanol elution, then with 95% ethanol elution, eluent flow rate is 2BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 24.12%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 3g and the Quercetin 7g after separation, add adjuvant, be prepared into tablet.
embodiment 4
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 1 hour for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 0.5 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin AB-8 to carry out separation, first with water elution, obtains eluent I; Then with 50% ethanol elution, then with 90% ethanol elution, eluent flow rate is 1BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 24.95%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 7g and the Quercetin 3g after separation, add adjuvant, be prepared into capsule.
embodiment 5
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 3 hours for the first time, 2 hours for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 60% ethanol elution, then with 95% ethanol elution, eluent flow rate is 4BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.13%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 5g and the Quercetin 5g after separation, add adjuvant, be prepared into drop pill.
embodiment 6
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 55% ethanol elution, then with 90% ethanol elution, eluent flow rate is 2BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 26.21%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 7g and the Quercetin 3g after separation, add adjuvant, be prepared into tablet.
embodiment 7
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 2 hours for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 60% ethanol elution, then with 95% ethanol elution, eluent flow rate is 3BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 24.79%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 4g and the Quercetin 6g after separation, add adjuvant, be prepared into capsule.
embodiment 8
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 2 hours for the first time, 2 hours for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin AB-8 to carry out separation, first with water elution, obtains eluent I; Then with 50% ethanol elution, then with 90% ethanol elution, eluent flow rate is 2BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.62%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 5g and the Quercetin 5g after separation, add adjuvant, be prepared into drop pill.
embodiment 9
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1.5 hours for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1 hour for the first time, 1 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin 1X-5 to carry out separation, first with water elution, obtains eluent I; Then with 55% ethanol elution, then with 95% ethanol elution, eluent flow rate is 2.5BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.89%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 4.5g and the Quercetin 5.5g after separation, add adjuvant, be prepared into tablet.
embodiment 10
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 3 hours for the first time, 2 hours for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 55% ethanol elution, then with 95% ethanol elution, eluent flow rate is 2BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 24.91%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 5.5g and the Quercetin 4.5g after separation, add adjuvant, be prepared into drop pill.
embodiment 11
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 2.5 hours for the first time, 1.5 hours for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin AB-8 to carry out separation, first with water elution, obtains eluent I; Then with 60% ethanol elution, then with 95% ethanol elution, eluent flow rate is 3.5BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.54%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 2g and the Quercetin 8g after separation, add adjuvant, be prepared into injectable powder.
embodiment 12
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 2.5 hours for the first time, 1.5 hours for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1.5 hours for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 54% ethanol elution, then with 93% ethanol elution, eluent flow rate is 4BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 24.86%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 6.5g and the Quercetin 3.5g after separation, add adjuvant, be prepared into drop pill.
embodiment 13
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 3 hours for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 0.5 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 59% ethanol elution, then with 94% ethanol elution, eluent flow rate is 3.5BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.10%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 3.5g and the Quercetin 6.5g after separation, add adjuvant, be prepared into injectable powder.
embodiment 14
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 1 hour for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 0.5 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin AB-8 to carry out separation, first with water elution, obtains eluent I; Then with 58% ethanol elution, then with 92% ethanol elution, eluent flow rate is 1.5BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.74%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 2.5g and the Quercetin 7.5g after separation, add adjuvant, be prepared into capsule.
embodiment 15
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 1.5 hours for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1.5 hours for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 55% ethanol elution, then with 95% ethanol elution, eluent flow rate is 2.5BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 26.08%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 7.5g and the Quercetin 2.5g after separation, add adjuvant, be prepared into tablet.
embodiment 16
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 3 hours for the first time, 2 hours for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1 hour for the first time, 1 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin AB-8 to carry out separation, first with water elution, obtains eluent I; Then with 50% ethanol elution, then with 95% ethanol elution, eluent flow rate is 3BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.71%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 4.1g and the Quercetin 5.9g after separation, add adjuvant, be prepared into drop pill.
embodiment 17
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 2.5 hours for the first time, 1 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1 hour for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin X-5 to carry out separation, first with water elution, obtains eluent I; Then with 60% ethanol elution, then with 90% ethanol elution, eluent flow rate is 1BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 25.97%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 6.1g and the Quercetin 3.9g after separation, add adjuvant, be prepared into tablet.
embodiment 18
(1) get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, heating and refluxing extraction 2 times, 3 hours for the first time, 2 hours for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 1.5 hours for the first time, 0.5 hour for the second time, filtrate merged to obtain extracting solution II; Merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopts macroporous resin AB-8 to carry out separation, first with water elution, obtains eluent I; Then with 50% ethanol elution, then with 95% ethanol elution, eluent flow rate is 1BV/h, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, Fructus Hippophae total flavones.After testing, product is 24.63%.
(2) isorhamnetin is separated with Quercetin;
(3) get isorhamnetin 5.5g and the Quercetin 4.5g after separation, add adjuvant, be prepared into drop pill.
embodiment 19
(1) get Fructus Hippophae medical material, after being pulverized, add ethyl acetate and ethanol, heating and refluxing extraction, obtain extracting solution I, medicinal residues add ethanol, and heating and refluxing extraction obtains extracting solution II, merge extractive liquid, I and II, be condensed into extractum, use dissolve with ethanol extractum, adopt macroporous resin X-5 to carry out separation to it, first with water elution, obtain eluent I; Then with ethanol elution 2 times, the volumetric concentration of eluting ethanol is 60% for the first time, and the volumetric concentration of eluting ethanol is 90%% for the second time, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, obtain Fructus Hippophae total flavones extract; After testing, product is 24.01%.
(2) isorhamnetin and Quercetin is separated;
(3) take isorhamnetin and Quercetin, add adjuvant, be prepared into drop pill.
embodiment 20
(1) get Fructus Hippophae medical material, after being pulverized, add ethyl acetate and the ethanol of volume ratio 1:2, heating and refluxing extraction, obtain extracting solution I, medicinal residues add ethanol, and heating and refluxing extraction obtains extracting solution II, merge extractive liquid, I and II, be condensed into extractum, use dissolve with ethanol extractum, adopt macroporous resin AB-8 to carry out separation to it, first with water elution, obtain eluent I; Then with ethanol elution 2 times, the volumetric concentration of eluting ethanol is 55% for the first time, and the volumetric concentration of eluting ethanol is 95% for the second time, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, obtain Fructus Hippophae total flavones extract; After testing, product is 24.89%.
(2) isorhamnetin and Quercetin is separated;
(3) take isorhamnetin and Quercetin, add adjuvant, be prepared into drop pill.
embodiment 21
(1) get Fructus Hippophae medical material, after being pulverized, add ethyl acetate and the ethanol of volume ratio 1:2, heating and refluxing extraction, obtain extracting solution I, medicinal residues add ethanol, and heating and refluxing extraction obtains extracting solution II, merge extractive liquid, I and II, be condensed into extractum, use dissolve with ethanol extractum, adopt macroporous resin X-5 to carry out separation to it, first with water elution, obtain eluent I; Then with ethanol elution 2 times, the volumetric concentration of eluting ethanol is 60% for the first time, and the volumetric concentration of eluting ethanol is 90% for the second time, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, obtain Fructus Hippophae total flavones extract; After testing, product is 25.74%.
(2) isorhamnetin and Quercetin is separated;
(3) take isorhamnetin and Quercetin, add adjuvant, be prepared into drop pill.
Compositions disclosed by the invention, those skilled in the art also can realize by adding the mode of other auxiliary elements; Also can be by extracting after Fructus Hippophae total flavones, the separated mode of removing other compositions is controlled at the content of isorhamnetin and Quercetin in scope of the present invention.Embodiments of the invention are only the specific descriptions to technical scheme, are not the restrictions to technical scheme.Those skilled in the art all fall into protection scope of the present invention not changing the replacement done under the condition of flesh and blood of the present invention or change.

Claims (10)

1. a Chinese medicine composition for Cardiovarscular, comprises the component of following percentage by weight: isorhamnetin 20~80%, Quercetin 20~80%.
2. Chinese medicine composition according to claim 1, is characterized in that, described constituent content is: isorhamnetin 30~70%, 30~70% Quercetins.
3. Chinese medicine composition according to claim 2, is characterized in that, described constituent content is:
Isorhamnetin 40~60%, Quercetin 40~60%.
4. Chinese medicine composition according to claim 3, is characterized in that, described constituent content is: isorhamnetin 60%, Quercetin 40%.
5. a preparation method for the Chinese medicine composition described in claim 1-4, comprises the following steps:
(1) get Fructus Hippophae medical material, after being pulverized, add ethyl acetate and ethanol, heating and refluxing extraction, obtain extracting solution I, medicinal residues add ethanol, and heating and refluxing extraction obtains extracting solution II, merge extractive liquid, I and II, be condensed into extractum, use dissolve with ethanol extractum, adopt nonpolar or low pole macroporous resin to carry out separation to it, first with water elution, obtain eluent I; Then with ethanol elution 2 times, the volumetric concentration of eluting ethanol is 50%~60% for the first time, and the volumetric concentration of eluting ethanol is 90%~95% for the second time, obtains eluent II, reclaim, and concentrating under reduced pressure, dry, obtain Fructus Hippophae total flavones extract;
(2) isorhamnetin and Quercetin is separated;
(3) take isorhamnetin and Quercetin, add adjuvant, be prepared into various dosage forms.
6. the preparation method of Chinese medicine composition according to claim 5, it is characterized in that, the described extraction process of step (1) is: get Fructus Hippophae medical material, the ethyl acetate and 70% ethanol that after being pulverized, add volume ratio 1:2, reflux 1 hour, extract 2 times, 1~3 hour for the first time, 1~2 hour for the second time, filtrate merges to obtain extracting solution I, medicinal residues add 70% ethanol, heating and refluxing extraction 2 times, 0.5~1.5 hour for the first time, 0.5~1 hour for the second time, filtrate merges to obtain extracting solution II, merge extractive liquid, I and II, be condensed into extractum, with 50% dissolve with ethanol extractum, adopt nonpolar or low pole macroporous resin to carry out separation to it, first with water elution, obtain eluent I, then with 50%~60% ethanol elution, then with 90%~95% ethanol elution, obtain eluent II, reclaim, concentrating under reduced pressure, dry, obtain Fructus Hippophae total flavones extract.
7. according to the preparation method of the Chinese medicine composition described in claim 5 or 6, it is characterized in that, the volume ratio of ethyl acetate and ethanol is 1:2.
8. according to the preparation method of the Chinese medicine composition described in claim 5 or 6, it is characterized in that, the volumetric concentration of the ethanol of eluting for the first time that step (1) is described is 60%; The volumetric concentration of eluting ethanol is 90% for the second time.
9. according to the preparation method of the Chinese medicine composition described in claim 5-8, it is characterized in that, the described elution flow rate of step (1) is 1~4BV/h, is preferably 1~2BV/h, more preferably 2BV/h.
10. according to the preparation method of the Chinese medicine composition described in claim 5-9, it is characterized in that macroporous resin AB-8 or X-5 that step (1) is described, more preferably X-5.
CN201210217297.8A 2012-06-28 2012-06-28 Traditional Chinese medicine composition for treating cardiovascular diseases and preparation method thereof Pending CN103505451A (en)

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Application publication date: 20140115