CN1883541A - A Chinese medicinal preparation for treating cardiovascular and cerebrovascular disease, its preparation method and use - Google Patents
A Chinese medicinal preparation for treating cardiovascular and cerebrovascular disease, its preparation method and use Download PDFInfo
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- CN1883541A CN1883541A CN 200610031698 CN200610031698A CN1883541A CN 1883541 A CN1883541 A CN 1883541A CN 200610031698 CN200610031698 CN 200610031698 CN 200610031698 A CN200610031698 A CN 200610031698A CN 1883541 A CN1883541 A CN 1883541A
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- cerebrovascular disease
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- hirudin
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Abstract
The invention provides a Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases, preparing process and use, wherein the preparation is prepared from total astragalus root saponins and hirudin. The preparation can be used for treating coronary disease, angina pectoris, cerebral hemorrhage, cerebral thrombus and cerebral embolism.
Description
Technical field
The invention discloses a kind of Chinese medicine preparation and its production and use, relate in particular to a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease and its production and use.
Background technology
The World Health Organization (WHO) points out: threatening the No.1 killer of human health is cardiovascular and cerebrovascular disease.Have sickness rate height, mortality rate height, epidemiology characteristics that disability rate is high.About 1,670 ten thousand people that cardiovascular and cerebrovascular disease is died from the annual whole world account for 29.2% of total death toll.Along with the aging of social population, the sickness rate of cardiovascular and cerebrovascular disease increases year by year.China has hyperpietic 1.6 hundred million people, about 1.6 hundred million people of dyslipidemia, about 2.4 hundred million people of overweight, about 7,000 ten thousand people of obesity patient at present.The sickness rate of China's apoplexy is higher, is Hesperian 4 times.China every year, the number because of cardiovascular and cerebrovascular disease death was 2,600,000 people, accounted for 416 of total death toll.Not long ago one investigation finds that China not only sickness rate of hypertension, coronary heart disease, apoplexy raises year by year, and age of onset presents rejuvenation trend also in advance, and the crowd's sickness rate below 40 years old accounts for 206.
The basic cause of disease of cardiovascular and cerebrovascular disease is an atherosclerosis, and causes that the most direct reason of cardiovascular and cerebrovascular disease is a hyperlipidemia.At ordinary times we said " three-hypers ", just be meant hyperlipidemia, hypertension, hyperglycemia.Prescribe a time limit when blood fat (mainly referring to cholesterol and triglyceride) surpasses normal value, just be called hyperlipemia, it is the foul disease that affluent life brings, and it is carrying out unconsciously to the infringement of human body, and is general.The infringement of a series of hearts that fearful is causes thus, brain, kidney.Its development step is such: hyperlipemia → sclerosis of blood vessels → blood pressure increases → cerebral ischemia → cordis and cerebral accident (being apoplexy or coronary heart disease).Senile disease such as coronary heart disease, apoplexy, hypertension, senile dementia, diabetes all may merge hyperlipemia.Therefore prevention and treatment cardiovascular and cerebrovascular disease the most important thing is blood fat reducing, and prevention of arterial is atherosis, could reduce the cardiovascular and cerebrovascular disease M ﹠ M like this, could prolong human longevity.
The Radix Astragali is the key medicine of invigorating qi and benefiting blood; Having benefit, to defend consolidating superficial resistance, diuretic swollen clearly; effect such as promoting pus discharge and tissue regeneration strengthening, invigorating the spleen and replenishing QI; among the people be usually used in treating spontaneous perspiration, night sweat, arthralgia due to stagnation of blood, edema, cellulitis do not burst or burst do not hold back for a long time, interior part of band is empty, the disease of diarrhea due to hypofunction of the spleen and all weakness of QI blood deficiency; Radix Astragali total saponins is one of main active ingredient of the Radix Astragali, and its research in effect aspect the cardiovascular and cerebrovascular disease is embodied in the following aspects:
1, have the thrombotic effect of remarkable anti-experimental character, and the energy anticoagulant, PGI improved
2With the NO level, fall to TXA
2/ PGI
2Ratio, mechanism of action with improve PGI
2Relevant with the NO level;
2, can reduce senile rat whole blood contrast viscosity and plasma viscosity, shorten erythrocyte electrophoretic time, reduce packed cell volume;
3, significantly antithrombotic forms, and the energy anticoagulant, reduces GMP-140 content, reduces TXA
2/ PGI
2Ratio;
4, the amount of the minimizing rat brain arterial thrombosis of energy significance increases ischemic tissue's antioxidative level.
Hirudo in the side, the medicinal argumentation to it in China's TCM Document is a lot of, calls as Compendium of Material Medica: " salty walk, the bitter blood that wins.The salty hardship of Hirudo to remove blood-retention, is a Liver Channel blood system medicine, so can lead to the poly-blood of Liver Channel." " book on Chinese herbal medicine converge with speech " have: " Hirudo, by the medicine of stagnant blood, blood stasis also.", " book on Chinese herbal medicine through hundred kinds of records ": " Hirudo happiness anthropophagy's blood, and property slow be apt to into, slow then hemopoietic is not hindered, and is apt to into then hard long-pending easily broken, borrows its power attacking the stagnating of accumulating in the course of time, from favourable and harmless also.”
The pharmacology aspect, Hirudo has anticoagulant, anti-fibrinolytic, anticoagulant reduces the effect of whole blood specific viscosity.Modern medicine proves, contains polypeptide element, heparin, antithrombotic element in the Hirudo, and main component is a protein, therefrom isolates hirudin, has stronger antithrombase effect.Hirudin can also suppress the inductive platelet aggregation of ADP, reduces the blood viscosity, regulates 6-keto-PGF
10And TXB
2Balance has and significantly draws thrombotic effect.In addition, Hirudo can reduce serum total cholesterol and the triglyceride of bait hyperlipemia rabbit, reduces the content of the serum cholesterol of experimental hyperlipidemia white mice, and similar to the clofibrate effect.In addition; also has the effect that improves cardiac status; effect to cardiac muscle picked-up RD is observed; the proof Hirudo has the effect that to a certain degree increases the myocardial nutrition blood flow; tissue ischemia, anoxia are had protective effect, but easily hinder healthy energy, if with Radix Astragali compatibility; then have and make assist mutually wonderful, the merit of playing QI invigorating removing blood stasis, promoting blood circulation to restore menstrual flow altogether mutually.
Summary of the invention
It is the Chinese medicine preparation that crude drug is made with Radix Astragali total saponins and hirudin that one of purpose of the present invention provides a kind of.
Two of purpose of the present invention provides the preparation method in order to the alleged preparation of preparation the present invention.
Three of purpose of the present invention provides the purposes of the alleged preparation of the present invention aspect the treatment cardiovascular and cerebrovascular disease.
Through a large amount of testing and verifications, curative effect is preferably arranged in each crude drug infra column weight amount ratio range in the prescription:
Radix Astragali total saponins 320-957; Hirudin 66-198.
Preferential weight proportion is:
Radix Astragali total saponins 478-798; Hirudin 99-165.
The optimum weight proportioning is:
Radix Astragali total saponins 638; Hirudin 132.
Press practice of pharmacy, preparation of the present invention can be various clinical medicine dosage forms, can be tablet, pill, capsule, soft capsule, granule, suspensoid, drop pill, slow, controlled release agent, oral liquid, injection, aerosol, suppository, any in the middle of the subcutaneous administration agent.
The preparation method of preparation of the present invention is as follows:
(1) gets a certain amount of Radix Astragali, be ground into coarse powder, use 35%-95% alcohol reflux 1-3 time, each 1-3 hour, for the first time doubly measure ethanol, doubly measure ethanol with 3-9 for the second time, reclaim ethanol, merge extractive liquid, with 4-12, concentrate, drying gets Radix Astragali total saponins, and is standby;
(2) get a certain amount of Hirudo, pulverize, add the pre-cold acetone (18 ℃) of the 65%-90% of 5-15 times of volume then, 2-6 ℃ was stirred 5-15 minute down, adds sodium oxide and trichloroacetic acid again and (make its concentration be respectively 0.2-0.5molL
-1And 0.1-0.4molL
-1, pH2.5-3.5), stirred 15-45 minute, centrifugal then (3000rpm * 10min), abandon supernatant, add 80% cold acetone of its volume 1/3 in the precipitation, extracting 1-3 time, each 3000 * 5min is centrifugal, collect supernatant, merge the cold acetone (18 ℃) of 1-3 times of volume of extract adding several times, left standstill 1-3 hour, it is centrifugal again that (5000rpm * 15min) abandons supernatant, collecting precipitation, dry hirudin crude product, the reuse anion-exchange chromatography of getting, and collect each peak and detect the activity at each peak, with the active peak lyophilization of collecting, again by the further purification hirudin of gel permeation chromatography method crude product, measure the activity of each section eluent after, active peak is concentrated, with the desalination of Sephadex G25 post, the protein solution that obtains is carried out lyophilization, cryopreservation, promptly get hirudin, standby;
(3) get (1) gained Radix Astragali total saponins and (2) gained hirudin, pulverize separately becomes mixing behind the fine powder, and by adding suitable adjuvant, technology can make the alleged preparation of the present invention routinely again.
Used adjuvant is conventional excipient in the preparation of the present invention, as solvent, disintegrating agent, correctives, antiseptic, coloring agent, binding agent etc.
Prescription of the present invention is simple, and the medicine source is abundant, and determined curative effect, and toxic and side effects is little, is fit to the industrialization mass production, has vast market prospect.
Preparation of the present invention can be used for treating all kinds of cardiovascular and cerebrovascular diseases, for example coronary heart disease, angina pectoris, cerebral hemorrhage, cerebral thrombosis, cerebral embolism etc.These pharmacological actions can prove by following pharmacodynamic experiment:
Experiment one: the present invention's prescription is to the protective effect of acute cerebral infarction
Line bolt method is caused the therapeutical effect of reperfusion injury after the focal cerebral ischemia in rats: at first, set up line bolt method and cause the focal cerebral ischemia in rats model, 4h pours into again behind ischemia, can cause that rat produces tangible behavior disorder and focal cerebral infarction.Then, observing the influence of pouring into the brain injury that causes again after the present invention writes out a prescription to focal cerebral ischemia on this model, and compare with negative group of physiology saline and nimodipine group, found that the present invention's focal cerebral ischemia that this model is caused of writing out a prescription has the obvious treatment effect, can significantly reduce the infarct size of nibbling after pouring into again, histopathological examination is the result also show, the neurocyte lesion degree also obviously alleviates.The present invention's prescription also can improve the apoplexy rat blood and glue, gathers, coagulates state, and anticoagulant increases the expression of SOD, the antioxidant radical damage.Prompting originally can improve apoplexy hemorheology of rat index, confirms that from pathology we have the effect of obvious anti-cerebral ischemia and protection brain cell.
Table 1 the present invention prescription to MCAO cause rat cerebral infarction tissue weight influence (administration 3d, x ± s, n=10)
| Group | Dosage/mg.kg -1 | Cerebral index (g/100g body weight) | Infraction brain weight percentage ratio/% | Unusual nervous symptoms scoring | ||
| 24h | 48h | 72h | ||||
| Sham Model Buddhist nun film Horizon the present invention prescription | - - 3.0 240 120 60 | 0.48±0.06 0.57±0.04 ΔΔ 0.51±0.03 ** 0.51±0.05 ** 0.52±0.02 ** 0.53±0.04 * | 0.00±0.00 32.03±3.83 ΔΔ 19.15±5.21 ** 17.24±2.54 ** 17.15±2.61 ** 22.77±4.57 ** | 0.0±0.0 5.7±1.2 ΔΔ 3.3±0.9 ** 3.5±1.6 ** 3.5±1.4 ** 4.2±2.3 | 0.0±0.0 5.6±1.4 ΔΔ 3.2±0.8 ** 3.6±1.4 ** 3.6±1.6 ** 4.1±2.1 | 0.0±0.0 5.4±1.4 ΔΔ 3.1±0.6 ** 3.5±1.2 ** 3.4±1.1 ** 4.1±1.9 |
Table 2 cerebral ischemia hindbrain tissue pathology checking
| Group | Dosage mg/kg | The neurocyte cavity becomes | Inflammatory infiltration | Glial cells hyperplasia | Neuronal shrinkage | Downright bad |
| Model Buddhist nun's film Horizon the present invention prescription | - 3.0 240 120 60 | +～++ + ±～+ ±～+ ±～+ | - - - - - | ± -～± - - - | ± - - -～± -～± | +～++ + ±～+ ±～+ ±～+ |
Annotate "-" and do not see pathological changes; " ± " accidental focal lesion; + slight pathological changes, surplus about 1/4 visual field of extent of disease; ++ about 1/3 visual field of moderate extent of disease.
Table 3 the present invention prescription to the influence of embolic type cerebral infarction hemorheology of rat (x ± sd, m=10)
| Group | Dosage/mg.kg -1 | Plasma viscosity (mpas) | Erythrocyte sedimentation rate (mm) | Hematocrit (mm) |
| Model group sham operated rats Buddhist nun film Horizon the present invention prescription | - 3.0 60 120 240 | 2.13±0.74 ΔΔ 1.12±0.22 1.40±0.27* 1.76±0.81 1.41±0.32* 1.44±0.53* | 1.38±1.47 1.15±0.71 1.57±0.61 1.26±0.88 1.55±1.30 1.56±1.24 | 42.45±4.72 46.40±4.12 43.14±3.13 42.50±9.93 42.80±5.87 44.46±4.48 |
Compare * P＜0.05, * * P＜0.01 with model group.
Table 4 the present invention prescription is to the influence of embolic type cerebral infarction rat platelet aggregation rate (x ± sd)
| Group | Dosage/mg.kg -1 | Dosage (mg/kgd) | Platelet maximum agglutination rate (%) |
| Model group sham operated rats Buddhist nun film Horizon the present invention prescription | - 3.0 60 120 240 | - - 18 60 120 240 | 60.9±14.0 Δ 48.6±8.8 40.7±8.5 ** 46.5±11.6 * 46.3±13.8 * 45.6±12.3 * |
Compare with model group, * P＜0.05, * * P＜0.01,
Table 5 the present invention prescription to line bolt method cause MDA, SOD in the cerebral infarction rat cerebral even slurry influence (x ± sd, n=8)
| Group | Dosage (mg/kgd) | MDA(nmol/mgprot) | SOD(U/mgprot) |
| Model group sham operated rats Buddhist nun film Horizon the present invention prescription | - - 18 60 120 240 | 4.075±1.926 3.167±0.447 3.857±0.896 4.971±1.165 4.902±1.204 4.764±1.034 | 45.18±15.11 ΔΔ 71.64±19.64 72.75±12.92** 54.28±10.42 61.28±9.30* 72.71±20.79** |
Compare * P＜0.05, * * P＜0.01 with model group.Compare Δ P＜0.05, Δ Δ P＜0.01 with sham operated rats.
Experiment two: the present invention writes out a prescription and suppresses thrombus in vivo formation
Experimental technique
Get 70 of healthy SD rats, be divided into 5 groups at random, 14 every group.Model group (equivalent distilled water), positive drug group (aspirin 25mg/kgd), the present invention's large, medium and small three dosage groups (240mg/kgd, 120mg/kgd, 60mg/kgd) of writing out a prescription.
Administering mode is a gastric infusion, and once a day, administration is 10 days altogether.Last administration fasting the previous day.After the last administration 1 hour, rat was with 0.6% pentobarbital sodium intraperitoneal injection of anesthesia, 0.5ml/100g, and fixedly postabdomen sterilization of dorsal position is opened the abdominal cavity from ventrimeson, exposes and also separates postcava, in the place's ligation of left renal vein lower horizontal, and sews up the abdominal cavity.After the ligation 2 hours, reopen the abdominal cavity, 2cm clamps postcava with mosquito forceps in the place below ligation, takes out this section blood vessel, and official jargon is cut in stringer open rapidly, and removal of thromboses on filter paper dips in and does unnecessary bloodstain, weighing weight in wet base.Put into 37 ℃ of baking oven intensive dryings then 24 hours.The weighing dry weight.The The data EXCEL software that obtains carries out F check and T ' check.
Experimental result
The present invention's prescription all has obvious minimizing effect to the weight and the length of the postcava thrombosis that ligation damage tube wall causes, and is comparatively speaking, big not as good as the influence of weight to the influence of thrombosis length.The results are shown in Table 29.
Table 29 the present invention prescription to the influence of rat postcava thrombosis (x ± sd, n=10)
| Group | Dosage (mg/kgd) | Thrombosis length (mm) | Wet weight of thrombus (mg) | Thrombosis dry weight (mg) |
| Model group positive drug the present invention prescription | - 25 60 120 240 | 12.15±4.47 4.07±1.94 ** 8.25±3.49* 9.17±2.92 5.15±2.38 ** | 35.69±12.66 6.29±4.73 ** 23.42±15.17 * 21.42±6.68 ** 10.08±10.99 ** | 10.85±5.38 1.79±1.53 ** 10.67±6.40 7.25±3.22 2.85±3.56 ** |
Compare * P＜0.05, * * P＜0.01 with model group.
Experiment conclusion
The present invention's prescription has certain inhibitory action to the postcava thrombosis that ligation damage tube wall causes.
Ligation rat postcava because of hypoxic-ischemic activates neutrophilic granulocyte and platelet, activate blood coagulation system simultaneously, and fibrinolytic weakens relatively.The present invention writes out a prescription and can alleviate the doing of postcava thrombosis, weight in wet base, show that the present invention writes out a prescription and has the effect that suppresses venous thrombosis, may bring into play anti-phlebothrombosis effect by improving fibrinolytic.Aspirin then has significant anticoagulant, and antithrombotic forms.
Experiment three: the present invention writes out a prescription to the amnemonic influence of local rats with cerebral ischemia
Apoplexy causes ischemic brain infarction, the neuron major injury, and function is impaired, and this is to cause the main cause of patient's apoplexy sequela clinically.We have observed the present invention's prescription to the amnemonic influence of local rats with cerebral ischemia.The result shows that the present invention writes out a prescription to the dysmnesia effect of having clear improvement.
Experiment four: the present invention writes out a prescription to the focal cerebral ischemia in rats influence of (convalescent period)
Electrocoagulation blocking-up rat brain medium-sized artery is adopted in this test, and ligation homonymy common carotid artery, cause the focal cerebral ischemia model, the influence of the present invention's prescription to indexs such as the convalescent nervous symptoms in brain medium-sized artery blocking-up back, cerebral infarction scope and pathological examinations observed in administration 7 days.The result shows: the present invention's prescription can obviously improve the neurobehavioral obstacle, obviously reduces the cerebral infarction scope, and the neurocyte lesion degree obviously is lighter than model group.
The purpose of this experiment is to observe the present invention's prescription to the focal cerebral ischemia in rats influence of (convalescent period).
Test material
Medicine:
1. the present invention writes out a prescription, the laboratory preparation, and distilled water is made into desired concn during test.
2. nimodipine 20mg/ sheet, Tianjin pharmaceutical factory of central authorities produces (lot number 960418).Distilled water is made into 1mg/ml during test.
Electrocoagulator: (Hyfrecator Plus 7-797) U.S. BMS company produces.
Animal: SD kind rat, 50, male, 250-300g, Chinese Academy of Medical Sciences's Experimental Animal Center provides, the moving word in the quality certification number＜capital〉79209 R018 number.
Test method
Animal is divided into 5 groups at random: sham operated rats, model group, the present invention's 4g crude drug/kg dosage group of writing out a prescription, the present invention's 1g crude drug/kg dosage group of writing out a prescription, positive drug nimodipine group (10mg/kg).
Press the TamuraShi method, animal 3.5% chloral hydrate intraperitoneal injection of anesthesia (35mg/100g body weight) cuts skin along the zygomatic arch direction, separates temporalis, exposes cheekbone, cuts off and removes cheekbone with bone forceps, through subtemporal approach, opens 2 * 4mm
2The cranium window, the strip off pia mater encephali exposes the right side middle cerebral artery, electricity coagulates the one section middle cerebral artery (it is 4W that electricity coagulates output) between tractus olfactorius and the inferior cerebral vein, after this, separate homonymy common carotid artery and ligation, sham operated rats is only opened the cranium window, is not electricly coagulated middle cerebral artery but the ligation common carotid artery.The operation metaduodenum gives institute's reagent thing (model group, sham operated rats give the equivalent normal saline), steams again behind the wound suture and raises, and be administered once every day, successive administration seven days.Test and raising room temperature remain on 25.0 ± 1.0 ℃.
Postoperative first and third, seven days adopt single blind method by each treated animal nervous symptoms of following standard observation, carry out the behavior integration scoring.Standards of grading are with the acute stage standards of grading, and the result carries out statistical procedures by grade preface value method.
After the last scoring, the animal broken end is got brain, and operating microscope affirmation medium-sized artery has down been blocked in the rearmounted ice normal saline, removes olfactory bulb, cerebellum and brain stem, and crown 4 cuttves of cutting are cut 5 brain sheets altogether, put in 10% formalin.The second brain sheet is through paraffin embedding, dehydration, dyeing, and microscopically calculates the focus of infarct area and carries out statistical procedures through micrometer, and light microscopic is observed cerebral tissue neurocyte pathological changes and recovery situation down.
Result of the test
One. to the influence of rat nervous symptoms
Sham operated rats is not seen dystropy, and model group operation back was all seen tangible behavior disorder in 1～3 day, recovers to some extent, and with sham operated rats significant difference (P＜0.01) is arranged more all in the 7th day; The present invention's 240mg/Kg dosage group postoperative of writing out a prescription 1 day was that visible behavior disorder has clear improvement, and with model group significant difference (P＜0.05) was arranged relatively, and continued to 3～7 days; As seen 1～3 day behavior disorder of 120mg/Kg group postoperative improves trend, 7 days have clear improvement (P＜0.05); As seen 1 day visible improvement trend of positive drug nimodipine group postoperative obviously improved (P＜0.01) in 3～7 days.
Two. the present invention's prescription is to the influence of cerebral infarction scope
Table 3. the present invention prescription is to the influence of rat cerebral infarction scope
| Group | Dosage/Kg | Number of animals (n) | Infarct size (lattice, X ± SD) |
| Sham operated rats model group prescription group of the present invention prescription group of the present invention nimodipine group | 240mg 120mg 10mg | 10 10 10 10 10 | 0 660.0±365.5## 212.8±138.4** 465.0±203.3 402.6±212.1 |
Annotate: relatively compare * * P＜0.01 with model group in ##P＜0.01 with sham operated rats
By table 3 as seen, performed the operation back 7 days, model group rat art side ischemia is serious, and it is 660.0 ± 365.5 (lattice) that microscopically records infarct size; The present invention's 4g crude drug/Kg dosage group infarct size of writing out a prescription is 212.8 ± 138.4 (lattice), significantly reduces (P＜0.01) with model group; The 1g crude drug/Kg group cerebral infarct size reduces to some extent, but not statistically significant; Nimodipine group infarct size accounts for the brain tangent plane gross area and also as seen reduces trend.
Three. pathological examination
Find through the light microscopic pathological examination: the big brain gray matter boundary of visible diseased region disappears under the model group low power lens, and the diseased region canescence is light dyes, visible engrain around it.High power lens shows down, olistherozone is a slough, as seen cave in and the crack, neurocyte is most of downright bad, and residual neurocyte boundary is unclear, some karyon is thin narrow triangle or is non-structure state, kernel disappearance, periphery engrain district is microglia hypertrophy district, and it is big that cell becomes, and endochylema is abundant, include a large amount of tiny cavitys, nuclear is pressed against on one side.Sham operated rats is not seen above-mentioned pathological change, and neurocyte is arranged in order, and water breakthrough is not swollen, and kernel as seen; The present invention's downright bad olistherozone of 4g crude drug/Kg dosage group of writing out a prescription is not obvious, interstitial edema, neurocyte swelling are arranged, but nuclear still as seen, and glial cells hyperplasia is more obvious, but endochylema is not really abundant, and tiny cavity obviously reduces; The present invention's visible neutrophil in 1g crude drug/Kg dosage group and nimodipine group partial necrosis district of writing out a prescription soaks into, olistherozone (necrotic area) reduces to some extent, in the matter irregular little cavity is arranged between visible neurocyte in the necrotic area, its peripheral part neurocyte, endochylema have muddiness, karyon as seen, the part entoblast is clear.
This experiment causes the focal cerebral ischemia in rats model with electrocoagulation blocking-up rat brain medium-sized artery and ligation homonymy common carotid artery, and successive administration seven days has been observed the present invention's prescription to the convalescent therapeutical effect of this model.Experimental result shows, cause the focal cerebral ischemia in rats model after, visible neurobehavioral obstacle, the obviously visible down cerebral infarction kitchen range (olistherozone) of mirror, neurocyte necrosis in the visible olistherozone of pathological examination, karyon is thin narrow triangle or non-structure state, and kernel disappears.After giving the present invention and writing out a prescription 7 days, the animal nerve symptom has clear improvement, and the cerebral infarction scope obviously reduces, and the visible neurocyte degree of necrosis of pathological examination makes moderate progress than model group.Prompting: this medicine has therapeutical effect to cerebral infarction convalescent period.
Conclusion our experiments show that, preparation of the present invention all has good therapeutic effect for all kinds of cardiovascular disease.
Specific embodiment
The present invention be a kind of with Radix Astragali total saponins and hirudin be crude drug make in order to treat Chinese medicine preparation of all kinds of cardiovascular and cerebrovascular diseases and its production and use.
Further specify content of the present invention below by enumerating of specific embodiment, but only for reference, do not limit the scope of the invention.
Specific embodiment one
Get Radix Astragali total saponins 638mg and hirudin 132mg, pulverize separately becomes mixing behind the fine powder, adds the about 335ml of starch 600g and water, mixing, and pill, drying, coating or Bao Nong not promptly get ball.
Specific embodiment two
Get Radix Astragali total saponins 638mg and hirudin 132mg, pulverize separately becomes mixing behind the fine powder, adds B-cyclodextrin 120g, mixing, and drying adds the 0.5g stevioside, granulates, drying, coating or coating not promptly get granule.
Specific embodiment three
Get Radix Astragali total saponins 638mg and hirudin 132mg, pulverize separately becomes mixing behind the fine powder, adds starch 50g, dextrin 30g, mix homogeneously, the alcohol granulation with 85% is behind drying, the granulate, the magnesium stearate that adds granule total amount 3%, tabletting, coating or not coating promptly get sheet.
Specific embodiment four
Get Radix Astragali total saponins 638mg and hirudin 132mg, pulverize separately becomes mixing behind the fine powder, and the Capsules of packing into promptly gets capsule.
Specific embodiment five
The clinical practice of preparation of the present invention on the treatment hyperlipidemia:
Data and method:
(1) case is selected
Patient's 96 examples, male's 71 examples, women's 25 examples, age 40-68 year, average 54 years old.Two the result person of increasing 28 examples of serum total cholesterol (TC) and triglyceride (TC) among the 96 routine patients, the individual event cholesterol person of increasing 24 examples, the individual event triglyceride person of increasing 44 examples, complicated hypertension patient 44 examples, coronary heart disease 15 examples are divided into treatment group and matched group at random, every group 48 example.
(2) medicine is formed and preparation
Get Radix Astragali total saponins 0.5g and hirudin 0.1g, be ground into fine powder after, in incapsulating with fine powder.
(3) Therapeutic Method
Treat any fat-reducing medicament of stopping using in preceding 24 hours, the treatment group gives 5 of capsules of the present invention, and 3 times on the 1st, matched group gives gemfibrozil (Gem fibrozil) 300mg, and every day 3 times, 1 month is a course of treatment, evaluates curative effect after 1 course of treatment.
(4) observational technique
Respectively survey 1 TC, TC, HDL-C, prothrombin time before and after the treatment, low-density lipoprotein cholesterol (LDL-C) calculates with the Friedewald formula: LDL-C=TC-(HDL-C+1/5TG).
The result
(1) blood lipid level difference is not seen statistical significance (PC＜0.05) before treatment group and the treatment of control group, finishing the back result course of treatment shows: the treatment group falls TC and LDL-C is better than matched group (P＜0.01), fall the equal no significant difference of TC effect and HDL-C increasing (P＜0.05), see following table for details:
Subordinate list: the variation of two groups of treatment front and back lab index (M ± SD)
| TC | TG | HDL-C | LDL-C | ||
| The treatment of control group group | Control preceding 48 examples control the back 48 examples control preceding 48 examples control the back 48 examples | 7.40±0.8 6.01±1.01(↓18％) 7.43±.82 5.10±1.03(↓31％) | 3.67±.15 2.14±0.95(↓41％) 3.60±1.41 2.15±0.98(↓40％) | 0.77±0.30 0.81±10.34(↑5％) 0.81±0.33 0.86±0.16(↓5％) | 5.18±.33 4.55±1.26(↓12％) 5.52±1.27 4.40±1.17(↓25％) |
Annotate: every blood fat contrast P value＜0.01 before and after two groups of treatments.
(2) prothrombin time before and after the treatment
Two groups of treatment prothrombinogen times are in scope.Took medicine back 1 month, the matched group prothrombin time does not have significant change, and treatment group prolonged prothrombin is 14-19s totally 41 examples, and 13s person's 27 examples are not seen side effect such as subcutaneous hemorrhage in the therapeutic process.
Claims (7)
1, a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease is characterized in that raw materials used medicine and weight proportion thereof are:
Radix Astragali total saponins 320-957; Hirudin 66-198.
2, a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease as claimed in claim 1 is characterized in that the preferential weight proportion of crude drug is:
Radix Astragali total saponins 478-798; Hirudin 99-165.
3, a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease as claimed in claim 1 is characterized in that the optimum weight proportioning of crude drug is:
Radix Astragali total saponins 638; Hirudin 132.
4, a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease as claimed in claim 1 is characterized in that: described preparation is any dosage form on the pharmaceutics.
5, a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease as claimed in claim 4, it is characterized in that: described preparation can be a tablet, pill, capsule, soft capsule, granule, suspensoid, drop pill, slow, controlled release agent, oral liquid, injection, aerosol, suppository, any in the middle of the subcutaneous administration agent.
6, claim 1,2 or 3 described a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease, its preparation method is characterised in that:
(1) gets a certain amount of Radix Astragali, be ground into coarse powder, use 35%-95% alcohol reflux 1-3 time, each 1-3 hour, for the first time doubly measure ethanol, doubly measure ethanol with 3-9 for the second time, reclaim ethanol, merge extractive liquid, with 4-12, concentrate, drying gets Radix Astragali total saponins, and is standby;
(2) get a certain amount of Hirudo, pulverize, add the pre-cold acetone (18 ℃) of the 65%-90% of 5-15 times of volume then, 2-6 ℃ was stirred 5-15 minute down, adds sodium oxide and trichloroacetic acid again and (make its concentration be respectively 0.2-0.5molL
-1And 0.1-0.4molL
-1, pH2.5-3.5), stirred 15-45 minute, centrifugal then (3000rpm * 10min), abandon supernatant, add 80% cold acetone of its volume 1/3 in the precipitation, extracting 1-3 time, each 3000 * 5min is centrifugal, collect supernatant, merge the cold acetone (18 ℃) of 1-3 times of volume of extract adding several times, left standstill 1-3 hour, it is centrifugal again that (5000rpm * 15min) abandons supernatant, collecting precipitation, dry hirudin crude product, the reuse anion-exchange chromatography of getting, and collect each peak and detect the activity at each peak, with the active peak lyophilization of collecting, again by the further purification hirudin of gel permeation chromatography method crude product, measure the activity of each section eluent after, active peak is concentrated, with the desalination of Sephadex G25 post, the protein solution that obtains is carried out lyophilization, cryopreservation, promptly get hirudin, standby;
(3) get (1) gained Radix Astragali total saponins and (2) gained hirudin, pulverize separately becomes mixing behind the fine powder, and by adding suitable adjuvant, technology can make the alleged preparation of the present invention routinely again.
7, claim 1, the 2 or 3 described a kind of application of Chinese medicine preparation in the treatment cardiovascular and cerebrovascular disease for the treatment of cardiovascular and cerebrovascular disease.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102038940A (en) * | 2009-10-09 | 2011-05-04 | 伍丽娟 | Hirudin combination medicament for treating cardiovascular and cerebrovascular diseases |
| CN104547004A (en) * | 2014-12-22 | 2015-04-29 | 南宁市净雪皇生物工程有限公司 | Traditional Chinese medicine composition for resisting thrombus, resisting blood coagulation and reducing blood viscosity and preparation method and application thereof |
-
2006
- 2006-05-23 CN CN2006100316989A patent/CN1883541B/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102038940A (en) * | 2009-10-09 | 2011-05-04 | 伍丽娟 | Hirudin combination medicament for treating cardiovascular and cerebrovascular diseases |
| CN104547004A (en) * | 2014-12-22 | 2015-04-29 | 南宁市净雪皇生物工程有限公司 | Traditional Chinese medicine composition for resisting thrombus, resisting blood coagulation and reducing blood viscosity and preparation method and application thereof |
| CN104547004B (en) * | 2014-12-22 | 2019-01-18 | 南宁市净雪皇生物工程有限公司 | Traditional Chinese medicine composition for resisting thrombus, resisting blood coagulation and reducing blood viscosity and preparation method and application thereof |
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| CN1883541B (en) | 2010-06-16 |
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