CN1112198C - Thrombolytic medicine and its preparation and use - Google Patents
Thrombolytic medicine and its preparation and use Download PDFInfo
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- CN1112198C CN1112198C CN00112893A CN00112893A CN1112198C CN 1112198 C CN1112198 C CN 1112198C CN 00112893 A CN00112893 A CN 00112893A CN 00112893 A CN00112893 A CN 00112893A CN 1112198 C CN1112198 C CN 1112198C
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Abstract
The present invention relates to a thrombolysis medicine made of leafflower herbs or Vietnam leafflower herbs of sibling plants, emblic leafflower fruit, common leafflower herbs and matsumura leafflower herbs. The preparation method and a usage thereof in the field of medicine manufacture are used as new thrombolysis medicines for curing, preventing and recovering thromboembolic diseases and are used for curing, preventing, and recovering diseases of myocardial infarction, hypertension, angina pectoris, apoplexy, cerebral thrombosis, pulmonary embolism, limb artery and vein embolism, retina artery and vein embolism, etc.
Description
The present invention relates to Cacumen Securinegae Suffruticosae and the application of congener ethanol extract in pharmacy, particularly, relate to the application in preparation antithrombotic thrombosis drug, anti-myocardial infarction medicine, antihypertensive drug, treatment angina drug, treatment apoplexy medicine, anti-cerebral thrombosis medicine, anti-pulmonary infarction medicine, anti-thrombosis of retinal vein medicine and anti-thrombosis of retinal artery medicine of Cacumen Securinegae Suffruticosae and congener ethanol extract.
Statistical data shows that the cardiovascular system diseases that is caused by thrombosis and atherosclerosis is one of the human main cause of death and disease.Thrombotic disease (brain, the heart, extremity infraction etc.) sickness rate height, apoplexy, myocardial infarction become human dead principal element.70% is cerebral thrombosis in the apoplexy.Nearly hundred million patients need efficient, the low price medicine of anticoagulant, thrombolytic, activating blood and resolving stasis and treating.The formation of thrombosis and elimination key are the balance between tPA (tissue plasminogen activator, tissue-type plasminogen activator) and PAI-1 (inhibitor of activator of plasminogen, Plasminogen activator inhibitor-1).By the interaction between the two, the active height of PAI-1 is being regulated whole fibrinolytic process (Dawson etal., Atherosclerosis 1992,95:105) in the blood plasma.Clinical and experimental data shows that it is a breakneck factor that the activity of PAI-1 in the blood plasma raises, can cause the reduction of fibrin degradation effect, thereby cause a series of cardiovascular disease, as: (Charlton such as myocardial infarction, coronary artery thrombosis, Drug of theFuture 1997,22:45).Therefore, the activity of inhibition PAI-1 is a very important treatment target spot.Seek low-molecular-weight PAI-1 inhibitor and will find new and effective thrombolytic medicine.It is hemorrhage complication that the present thrombolytic medicine that uses clinically all has a common defective, while medical expense height, half-life weak point, and owing to be that macromole usually easily causes allergy.Because its unique mechanism of action, the PAI-1 inhibitor of high selectivity might be avoided this side effect.Big pharmacy group to the more American-European in recent years developed countries in this field is very interested, yet the small-molecular weight PAI-1 inhibitor of having found up to now is very few, Britain Xenova company has a microbe-derived chemical compound to finish in the animal body and in vitro tests, has now entered clinical (Xenova).Based on more than, develop new natural micromolecule PAI-1 inhibitor, and it is used for treatment, prevention and the recovery of thrombotic disease as the novel thrombolytic medicine, be used for myocardial infarction, hypertension, angina pectoris, apoplexy, cerebral thrombosis, pulmonary infarction and diseases such as thrombosis of retinal vein and thrombosis of retinal artery and be the approach of a new development antithrombotic reagent.Up to now, prior art is not ethanol extraction that raw material extracts is made thrombolytic drug as effective site or effective ingredient a report with Cacumen Securinegae Suffruticosae (Phyllanthusurinaria) or its congener Vietnam Cacumen Securinegae Suffruticosae or Fructus Phyllanthi or Herba Phyllanthi Urinariae or Herba Phyllanthi matsumuraes not also.
The object of the present invention is to provide a kind of with Cacumen Securinegae Suffruticosae (Phyllanthus urinaria), or the ethanol extraction of congener Vietnam Cacumen Securinegae Suffruticosae (Phyllanthus cochinchinensis) or Fructus Phyllanthi (P.emblica) or Herba Phyllanthi Urinariae (P.simplex) or Herba Phyllanthi matsumuraes (P.matsumurae) is made thrombolytic drug as effective site, the preparation method of this medicine is provided simultaneously, and at preparation antithrombotic thrombosis drug, anti-myocardial infarction medicine, antihypertensive drug, treatment angina pectoris disease medicament, treatment apoplexy medicine, anti-cerebral thrombosis medicine, anti-pulmonary infarction medicine, application in anti-thrombosis of retinal vein medicine and the anti-thrombosis of retinal artery medicine.
In order to realize purpose of the present invention, the invention provides following technical scheme:
A kind of thrombolytic drug is the medicine that raw material is made according to following method with Cacumen Securinegae Suffruticosae or Vietnam's Cacumen Securinegae Suffruticosae or Fructus Phyllanthi or Herba Phyllanthi Urinariae or Herba Phyllanthi matsumuraes:
Get Cacumen Securinegae Suffruticosae or Vietnam's Cacumen Securinegae Suffruticosae or Fructus Phyllanthi or Herba Phyllanthi Urinariae or Herba Phyllanthi matsumuraes, dry, pulverize dry powder, use methanol, industrial alcohol, aqueous acetone is let alone a kind of solvent and is at room temperature extracted 2-4 time, extracting solution is evaporated to dried extractum under 30 ℃-40 ℃, with the extractum n-butyl alcohol, ethyl acetate or contain a small amount of organic acid n-butyl alcohol suspendible, water gradation extraction, combining water layer, 40 ℃ are evaporated to small size, sparge dry dry powder then, be 0.1 in dry powder and pharmaceutically suitable carrier and/or excipient weight ratio: 99.9-99: 1 ratio is mixed with solid preparation; Or the liquid preparation preparation method is mixed with liquid preparation routinely.
The present invention also provides the preparation method of above-mentioned thrombolytic drug, get Cacumen Securinegae Suffruticosae or Vietnam's Cacumen Securinegae Suffruticosae or Fructus Phyllanthi or Herba Phyllanthi Urinariae or Herba Phyllanthi matsumuraes, dry, pulverize dry powder, use methanol, industrial alcohol, aqueous acetone is let alone a kind of solvent and is at room temperature extracted 2-4 time, extracting solution is evaporated to dried extractum under 30 ℃-40 ℃, with the extractum n-butyl alcohol, ethyl acetate or contain a small amount of organic acid n-butyl alcohol suspendible, water gradation extraction, combining water layer, 40 ℃ are evaporated to small size, carry out spray drying then and get dry powder, be 0.1 in dry powder and pharmaceutically suitable carrier and/or excipient weight ratio: 99.9-99: 1 ratio is mixed with solid preparation.
The present invention provides the another kind of preparation method of above-mentioned thrombolytic drug simultaneously, get Cacumen Securinegae Suffruticosae or Vietnam's Cacumen Securinegae Suffruticosae or Fructus Phyllanthi or Herba Phyllanthi Urinariae or Herba Phyllanthi matsumuraes, dry, pulverize dry powder, use methanol, industrial alcohol, aqueous acetone is let alone a kind of solvent and is at room temperature extracted 2-4 time, extracting solution is evaporated to dried extractum under 30 ℃-40 ℃, with the extractum n-butyl alcohol, ethyl acetate or contain a small amount of organic acid n-butyl alcohol suspendible, water gradation extraction, combining water layer, 40 ℃ are evaporated to small size, carry out spray drying then and get dry powder, the liquid preparation preparation method is mixed with liquid preparation routinely then.
The present invention also provides the application of above-mentioned thrombolytic drug in preparation antithrombotic thromboembolism, anti-myocardial infarction medicine, antihypertensive drug, treatment angina pectoris disease medicament, treatment apoplexy medicine, anti-cerebral thrombosis medicine, anti-pulmonary infarction medicine, anti-thrombosis of retinal vein medicine and anti-thrombosis of retinal artery medicine.
When the effective site of above-mentioned plant is used as medicine, can directly use, perhaps use with the form of pharmaceutical composition.This pharmaceutical composition contains 0.1 ~ 99%, is preferably 0.5 ~ 90% effective site, and all the other are acceptable on the materia medica, to nontoxic and inert pharmaceutically suitable carrier of humans and animals and/or excipient.
Described carrier is that one or more are selected from solid, semisolid and liquid diluent, filler and pharmaceutical preparation adjuvant, and described pharmaceutical composition is used with the form of per weight dose.But two kinds of form administrations of medicine oral administration of the present invention and injection (quiet notes, intramuscular injection).
Oral its solid or the liquid preparation taken is as powder, tablet, sugar-coat agent, capsule, granule supernatant liquid, syrup, drops etc.
Inject available its solid or liquid preparation, as injectable powder, solution type injection agent etc.
In order to understand essence of the present invention better, the pharmacological action result of the effective site (hereinafter to be referred as PUW) extracted of the ethanol extraction of the above-mentioned plant that obtains with preparation method of the present invention and the medicine formed with pharmaceutical carrier or excipient thereof illustrates its application in field of medicaments below.
1.PAI-1 suppress the screening active ingredients test
R-PAI-1 is that U.S. Molecular lnnovations lnc. produces, and urokinase is the Sigma product, and Chromozym U is that German Boehringer Mannheim produces.Institute's test agent is dissolved in DMSO by finite concentration, with r-PAI-1 hatching 10 minutes, adds urokinase and substrate Chromozym U then earlier, the reaction beginning was interrupted reaction with 32% acetic acid after 45 minutes, and 405nm wavelength place measures the absorption value of substrate catabolite.IC according to test determination Corilagin
50Be 10 μ g/ml.
2. acute toxicity test in mice
A. oral administration: ICR mice, male and female half and half, body weight 18-22g, after the fasting 12 hours, PUW irritates stomach with 0.4mL/10g, owing to can not ask median lethal dose(LD 50), so rely the amount of being subjected to requirement of experiment to experimentize by maximum, observed 14 days continuously, none animal dead, its maximum bad amount of being subjected to (MTD) is 5.6g/kg.
A. intravenous injection: the ICR mice, male and female half and half, body weight 18-22g, fasting is after 12 hours, and PUW, injected in 20 seconds and finishes from tail vein injection with 0.2ml/10g.Observed 14 days continuously, its median lethal dose(LD 50) is 259.6mg/kg (95% credibility interval: 222.4-303.1mg/kg).
3. rat tail point goes out blood test
PUW 10mg/kg after the disposable injection of male SD rat femoral vein, the animal tail point bleeding time
Slightly extend to 16.9 ± 1.3min from 14.6 ± 0.6min of normal saline group, and behind the quiet notes of heparin 100U/kg, the bleeding time then obviously extends to 37.1 ± 1.3min.Show that PUW does the time spent at the stronger thromboembolism preventing of generation, it is littler to hemorrhage influence.
4.PUW arachidonic acid is caused the thrombotic influence of mice
A. oral administration: inject a certain amount of arachidonic acid (AA) from male mice tail vein, observe dead mouse situation in the 30min, estimate medicine to thrombotic effect in the clear-headed animal body with the height of mortality rate.AA is with the 75mg/kg tail vein injection.Significance X
2Check is handled.The result shows that PUW 10mg/kg promptly has the effect suitable with the aspirin of 20mg/kg, and mortality rate is reduced to 53.3% from 80% of matched group.
A. intravenous injection: behind the quiet notes of PUW 2.5mg/kg, obviously reduce animal dead number (P>0.05), its effect of back of the quiet notes of the PUW of 5mg/kg is suitable with the aspirin of 10mg/kg, and mortality rate is reduced to 40% from 80% of matched group.
5.PUW to the thrombotic influence of electricity irritation rat carotid artery
Male SD rat, body weight 250-300g.Expose left common carotid artery and stimulate 7min with silvery electrode stimulating (the positive and negative electrode spacing is 1cm) with 1.5mA, the carotid artery flow amount is surveyed with the blood flow instrument, from stimulation begin to blood flow be the zero time be thrombus formation time (Oeclusion time, OT).
A. oral administration: the OT of normal saline group is 18.1 ± 1.6min, and aspirin 20mg/kg group is 34.2 ± 2.3min, and PUW 10, and the OT of 20mg/kg group is respectively 27.0 ± 2.6 and 35.0 ± 3.6min.
A. intravenous injection: the OT of normal saline group is 17.7 ± 0.8min, and 20mg/kg aspirin group is 27.8 ± 1.6min, and the OT of PUW 5,10 and 20mg/kg group is respectively 27.2 ± 1.7,31.2 ± 2.1 and 36.7 ± 1.9min.The result shows that the PUW of 5mg/kg promptly has the effect of tangible anti-electricity irritation rat carotid artery thrombosis, and its intensity is suitable with the 20mg/kg aspirin.
6. venous thrombosis effect
Male SD rat body weight 200-250g. opens the abdominal cavity with the anesthesia of 40mg/kg pentobarbital sodium along ventrimeson, free postcava and in the horizontal ligation of left renal vein it, close the abdominal cavity.After 1 hour, irritate stomach or from the femoral vein administration; After 1 hour, open the abdominal cavity, collect the embolus in the postcava, claim its weight in wet base, put 60 ℃ of roasting railway carriage or compartment bakings then and claim its dry weight after 20 hours.
A. oral administration: the dried weight in wet base of normal saline group thrombosis is respectively 4.1 ± 0.8 and 9.9 ± 2.0mg.20mg/kg aspirin group is respectively 1.0 ± 0.9 and 2.2 ± 2.3mg.20mg/kg PUW group
Thrombosis to do weight in wet base respectively be 1.3 ± 0.9 and 2.9 ± 2.0mg.
A. intravenous injection: the dried weight in wet base of normal saline group thrombosis is respectively 4.1 ± 0.5 and 9.9 ± 1.8mg.The dried weight in wet base of 10mg/kg aspirin group thrombosis is respectively 2.9 ± 0.5 and 6.1 ± 1.3mg.5,10 and the dry weight of 20mg/kg PUW group thrombosis be respectively 2.8 ± 0.6,2.2 ± 0.7 and 1.7 ± 0.6mg, the wet weight of thrombus of the above-mentioned dosage group of PUW respectively is 6.0 ± 1.1,5.2 ± 0.9 and 3.7 ± 1.0mg.
7.PUW thrombolytic effect: male SD rat, body weight 200-300g, improvement Peter method, left common carotid artery stimulates 5min with 2mA, with blood flow instrument continuous probe carotid artery flow amount.Stimulate to finish back to blood flow serves as that 50% before stimulating is thrombus formation time.20min after the thrombosis, PUW, all disposable intravenous injection of normal saline and urokinase.1h after the administration observes the revascularization situation, if occur leading to, then continues to observe vessel open state 1h again.With 〉=50% or≤25% stimulate before the blood flow person be judged to be again logical or continue after thromboembolism again, the vessel open degree is respectively nothing logical (PO) again, lead to again and the staggered appearance of thromboembolism (CR) again, three kinds of states of logical again back continuous openness (PP), the result shows, PUW is dosage correlation thrombolytic effect: 5mg/kg, and its recanalization rate is suitable with the 2000U/kg urokinase; 10mg/kg, its recanalization rate is 50%, is lower than 60% bolt rate again of 2000U/kg urokinase; None animal of normal saline group occurs logical again, and logical again back blood vessel open state shows as, and the normal saline group all continues thromboembolism; 2000U/kg urokinase open state is similar to the PUW of 5mg/kg: the 10mg/kgPUW group, its lasting recanalization rate is higher than the urokinase (the vessel open state sees Table 1) of 2000U/kg.The above results discloses, behind the disposable quiet notes, and thromboembolism effect again after PUW has stronger thrombolytic and prevents thrombolytic.
1h tremulous pulse open state drug dose (mg/kg) vessel open state score value behind the disposable quiet notes PUW thrombolytic of table 1
Continue the thromboembolism thromboembolism and lead to the staggered logical physiology salt 2ml/kg 800 water PUW 2.5 431 that continue again again
5.0 3 3 2
10.0 233 urokinase 2000U/kg, 34 1n=8 male rats
Table 2 PUW to thrombolytic effect drug dose thrombus formation time blood flow zero point of arterial thrombus the bolt number of logical again number/again/
(mg/kg) (min) time (min) sum leads to number normal saline 2ml/kg 7.5 ± 3.1 18.8 ± 3.6 0/8 0/0PUW 2.5 7.9 ± 2.7 20.8 ± 3.9 3/8* 2/3* again
5.0 8.1±3.4 18.7±4.3 5/8* 3/5*
10.0 7.7 ± 3.5 19.5 ± 4.0 6/8* 3/6* urokinase 2000U/kg, 7.4 ± 3.3 19.2 ± 4.4 5/8* 3/5*n=8 male rats, x ± s, * P<0.05 (X
2Test) compare with normal saline.
Above-mentioned pharmacodynamic result shows that oral and intravenous injection PUW all has very strong thrombolytic and anti-thrombosis function in multiple thrombus model.
8. mechanism of action
PUW is at external (the tissue-typeplasminogen activator of tissue plasminogen activator in the blood plasma that significantly improves, tPA) activity, reduce blood plasma 1-type activator of plasminogen mortifier (type-l plasminogen activator inhibitor, PAI-1) activity.In vivo test: behind the rat anesthesia, intravenous injection PUW 1.0mg/kg/min 20 minutes obviously reduces PAI-1 activity in blood plasma and the platelet, rising tPA activity, and prompting PUW brings into play anti thrombotic action by suppressing the PAI-1 activity and the tPA activity that raises.
In sum, PUW has following advantage as a kind of novel thrombolytic medicine:
1) comes from Cacumen Securinegae Suffruticosae (Phyllanthus urinaria) and congener Vietnam Cacumen Securinegae Suffruticosae thereof
(Phyllanthus cochinchinensis), Fructus Phyllanthi (P.emblica), Herba Phyllanthi Urinariae (P.simplex), Herba Phyllanthi matsumuraes (P.matsumurae), aboundresources, cheap.Extraction and processing technique are easy, can produce in batches.
2) oral and intravenous injection all can, the thrombolytic drug effect certainly, effect is strong.
3) overcome present clinical thrombolytic medicine commonly used and easily caused hemorrhage side effect.
4) basic avirulence after the oral and intravenous injection.
5) its thrombolytic mechanism is directly to suppress the PAI-1 activity in vivo and in vitro and rising tPA activity, is the natural micromolecule PAI-1 inhibitor of unique so far plant origin.
6) prevention, treatment and the recovery for myocardial infarction, hypertension, angina pectoris, apoplexy, cerebral thrombosis, pulmonary infarction and diseases such as thrombosis of retinal vein and thrombosis of retinal artery provides the novel thrombolytic medicine.
Further flesh and blood of the present invention is described below in conjunction with embodiment, but content of the present invention is not limited thereto.
Embodiment 1:
With fresh Cacumen Securinegae Suffruticosae (Phyllanthus urinaria) the aerial parts airing gathered, pulverize dry powder 15.42Kg.Then with extracting under the industrial alcohol room temperature more than 93% 4 times, extracting solution is evaporated to dried extractum 1365g under 40 ℃.With n-butanol layer dissolving, the suspension of extractum with n-butyl alcohol-acetic acid-water (4: 1: 5).With water layer extraction, combining water layer, 40 ℃ are evaporated to small size, carry out spray drying then and get dry powder (PUW) 401.7g.Check its dry powder (PUW) by high pressure liquid chromatography (HPLC), mainly contain two compositions, wherein Corilagin content is greater than 60% (as standard control, measuring content with the HPLC method routinely with pure corilagin).In dry powder and excipient weight ratio is that 9: 1 ratio adds excipient, makes capsule.
Embodiment 2:
Method by embodiment 1 makes Cacumen Securinegae Suffruticosae dry powder (PUW) earlier, is that 5: 1 ratio adds excipient in dry powder and excipient weight ratio, makes powder.
Embodiment 3:
Method by embodiment 1 makes Cacumen Securinegae Suffruticosae dry powder (PUW) earlier, is that 5: 1 ratio adds excipient in dry powder and excipient weight ratio, makes the sugar-coat agent.
Embodiment 4:
Method by embodiment 1 makes Cacumen Securinegae Suffruticosae dry powder (PUW) earlier, is that 2: 1 ratio adds excipient, pelletizing press sheet in dry powder and excipient weight ratio.
Embodiment 5:
With fresh Cacumen Securinegae Suffruticosae (Phyllanthus urinaria) the aerial parts airing gathered, pulverize dry powder 15.42Kg.Then with extracting under the industrial alcohol room temperature more than 93% 3 times, extracting solution is evaporated to dried extractum 1365g under 35 ℃.With n-butanol layer dissolving, the suspension of extractum with n-butyl alcohol-acetic acid-water (4: 1: 5).With water layer extraction, combining water layer, 40 ℃ are evaporated to small size, carry out spray drying then and get dry powder (PUW) 401.7g.Check its dry powder (PUW) by high pressure liquid chromatography (HPLC), mainly contain two compositions, wherein Corilagin content greater than 60% (with pure corilagin as standard control, measure content with the HPLC method routinely), dry powder is dissolved in the sterile water for injection, stirring makes molten, filter with aseptic suction funnel, aseptic again fine straining is sub-packed in the 2ml ampoule, and aseptic sealing by fusing gets injectable powder behind the frozen drying.
Embodiment 6:
Method by embodiment 1 or 5 makes Cacumen Securinegae Suffruticosae dry powder (PUW) earlier, and the oral liquid method for making is made oral liquid routinely.
Embodiment 7:
Method by embodiment 1 or 5 makes Cacumen Securinegae Suffruticosae dry powder (PUW) earlier, and in the water-soluble solution of dry powder, the paste-making method of refining sugar is routinely made syrup.
Embodiment 8:
Method by embodiment 1 or 5 makes Cacumen Securinegae Suffruticosae dry powder (PUW) earlier, and the method for drop pill is made drop pill routinely then.
Embodiment 9:
Method by embodiment 1 or 5 makes Cacumen Securinegae Suffruticosae dry powder earlier, adds the injection water then routinely, fine straining, and injection is made in the embedding sterilization.
Embodiment 10:
With fresh Cacumen Securinegae Suffruticosae Vietnam Cacumen Securinegae Suffruticosae Phyllanthus cochinchinensis aerial parts airing of gathering, pulverize dry powder 1Kg.Then with extracting under the industrial alcohol room temperature more than 93% 4 times, extracting solution is evaporated to dried extractum 90g under 40 ℃.With n-butanol layer dissolving, the suspension of extractum with n-butyl alcohol-acetic acid-water (4: 1: 5).With water layer extraction, combining water layer, 40 ℃ are evaporated to small size, carry out spray drying then and get dry powder 25g.Check its dry powder (PUW) by high pressure liquid chromatography (HPLC), mainly contain two compositions, wherein Corilagin content is greater than 60% (as standard control, measuring content with the HPLC method routinely with pure corilagin).In dry powder and excipient weight ratio is that 9: 1 ratio adds excipient, makes capsule.
Embodiment 11:
With the fresh congener Fructus Phyllanthi P.emblica branch and leaf airing gathered, pulverize dry powder 5Kg.Then with extracting under the industrial alcohol room temperature more than 93% 4 times, extracting solution is evaporated to dried extractum 450g under 40 ℃.With n-butanol layer dissolving, the suspension of extractum with n-butyl alcohol-acetic acid-water (4: 1: 5).With water layer extraction, combining water layer, 40 ℃ are evaporated to small size, carry out spray drying then and get dry powder (PUW) 150g.(HPLC) checks its dry powder by high pressure liquid chromatography, mainly contains two compositions, and wherein Corilagin content is greater than 60% (as standard control, measuring content with the HPLC method routinely with pure cotilagin).In dry powder and excipient weight ratio is that 9: 1 ratio adds excipient, makes capsule.
Embodiment 12:
With the fresh Herba Phyllanthi Urinariae P.simplex aerial parts airing gathered, pulverize dry powder 10Kg.Then with extracting under the industrial alcohol room temperature more than 93% 4 times, extracting solution is evaporated to dried extractum 985g under 40 ℃.With n-butanol layer dissolving, the suspension of extractum with n-butyl alcohol-acetic acid-water (4: 1: 5).With water layer extraction, combining water layer, 40 ℃ are evaporated to small size, carry out spray drying then and get dry powder 280g.(HPLC) checks its dry powder by high pressure liquid chromatography, mainly contains two compositions, and wherein Corilagin content is greater than 60% (as standard control, measuring content with the HPLC method routinely with pure corilagin).In dry powder and excipient weight ratio is that 9: 1 ratio adds excipient, makes capsule.
Embodiment 13:
Fresh the belonging to together of gathering planted 1 kilogram of Herba Phyllanthi matsumuraes P.matsumurae herb; airing, crushing and water-adding are fried in shallow oil and are carried 2 times; water liquid through macroporous adsorbent resin handle general glycoside; general glycoside is through the rough segmentation of silica gel short column chromatography; purified again chemical compound 1-acyl-3,6-hexahydroxy biphenyl diformyl glucose (Corilagin) 5.07g of getting.In Corilagin and excipient weight ratio is that 9: 1 ratio adds excipient, makes capsule.
Claims (9)
1, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in preparation antithrombotic thrombosis drug.
2, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in the anti-myocardial infarction medicine of preparation.
3, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in the preparation antihypertensive drug.
4, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in preparation treatment angina drug.
5, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in preparation treatment apoplexy medicine.
6, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in the anti-cerebral thrombosis medicine of preparation.
7, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in the anti-pulmonary infarction medicine of preparation.
8, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in the anti-thrombosis of retinal vein medicine of preparation.
9, Cacumen Securinegae Suffruticosae and the congener ethanol extract application in the anti-thrombosis of retinal artery medicine of preparation.
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