CN1449775A - Medicine composition for preventing and treating thrombosis and relative disease - Google Patents
Medicine composition for preventing and treating thrombosis and relative disease Download PDFInfo
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Abstract
The present invention relates to a new medicine composition, in particular, it is a natural medicine composition for preventing and curing thrombosis and related diseases. Said ivnention also provides its preparation method.
Description
The present invention relates to new pharmaceutical composition, particularly relate to and be used to prevent and treat thrombotic new natural drug composition, its preparation method, and be used for preventing and treat the application of the medicine of thrombosis and relevant disease in production.
Thrombotic disease as myocardium infarction, blood vessel embolism etc., is the serious harm human health, causes one of human body main causes of death.Thrombosis still is related a kind of important pathological process in numerous disease (as glomerulonephritis, the change of the diabetes small vessel disease etc.) pathogenesis.The change that blood vessel wall is impaired, blood constituent reaches blood flow state unusually is thrombotic fundamental cause.The clinical manifestation of thrombosis and thromboembolism and consequence depend on the size of thrombosis, the position of obstruction and the type of involved organs or tissue.When in the blood capillary of whole body the diffusivity thrombosis taking place, cause disseminated inravascular coagulation.The limb artery thromboembolism causes acrodynia, ischemic necrosis.Coronary artery thrombosis can cause angina pectoris, myocardial infarction.Carotid artery or cerebral artery thrombosis form or thromboembolism often shows as hemiplegia, disturbance of consciousness.In the normal blood cyclic process, platelet remains static.Yet in case vascular damaged takes place, platelet will combine and adhere to the subendothelial tissue that the damaged blood vessels place exposes with the blood plasma von Wllebrand factor by the Ib receptor of skin covering of the surface glycoprotein (GP) Ib-IX complex.Adherent platelet is activated by subendothelial tissue or the local thrombin that forms, and causes release reaction and arachidonic acid metabolic process, and then can cause platelet aggregation.The GP Ib/IIIa receptor that is activated forms cross-bridges by fibrinogen molecule between adjacent platelet, constitute the skeleton of platelet aggregation, finally causes thrombosis.The products such as TX A2 that platelet discharges also can be further and the plasma protein effect, promotes the formation of thrombosis.Therefore, suppressing hematoblastic effect in each stage effectively, is the important channel of prevention or treatment thrombosis disease.The antithrombotic reagent that generally uses clinically mainly comprises three classes at present: monoclonal antibody (Mc Ab), the peptide class of synthetic and non-peptide micromolecular material.For example, monoclonal antibody comprises and succeeding in developing and the anti-CD 61 epi-position GP IIb/IIIa monoclonal antibody 7E3 (C7EFab, trade name ReoPro) of humanization of clinical practice.In addition, the integrelin type cyclic peptide with sequence RGD (Alg-Gly-Asp) (its for the common characteristic sequence of platelet receptor aglucon) has also dropped into clinical practice (referring to No. 6168925, United States Patent (USP)).Non-peptide micromolecular medicine comprises that effect is relatively than the aspirin that limits to, Ticlopidine etc.Acute ischemic cardiovascular and cerebrovascular vessel onste excessively in, be used to suppress body intravascular coagulation process, prevent thrombosis and thrombosis to enlarge and thrombolytic medicine comprises heparin, streptokinase, urokinase, tissue plasminogen activator (tPA) etc.Yet the big multiaction of these medicines is single, and the production cost high price is also very expensive, and particularly present treatment for the cardiovascular and cerebrovascular vessel thrombus sequela still lacks highly effective medicine.
The inventor in conjunction with Chinese traditional medicine scientific principle opinion and modern pharmacology and clinical medicine experimental technique, designs and has prepared one group of new pharmaceutical composition in its long-term tcm clinical practice.Animal experiment study is the result show, these pharmaceutical compositions can suppress thrombosis and treatment relevant disease effectively.Clinic trial result proves that further pharmaceutical composition of the present invention can be used for prevention and treats the heart, cerebrovascular thrombosis, and the multiple relevant disease that comprises myocardial infarction, myocardial ischemia, cerebral vessels embolism, numb limbs and tense tendons and hemiplegia.
An object of the present invention is to provide a kind of new pharmaceutical composition, be characterised in that what said pharmaceutical composition was made up of Fel Ursi, Moschus, Calculus Bovis, Radix Ginseng Rubra, Radix Notoginseng, Squama Manis, Hirudo, Cornu Cervi Pantotrichum, Sanguis Draxonis and the Pheretima of the main ingredient of conduct basically.
Pharmaceutical composition preferred embodiment according to the present invention; wherein the content according to the weight ratio Fel Ursi is 0.01-1%, and Moschus is that 0.01-1%, Calculus Bovis are that 0.01-1%, Radix Ginseng Rubra are that 0.1-10%, Radix Notoginseng are that 0.1-10%, Squama Manis are that 0.1-10%, Hirudo are that 0.1-10%, Cornu Cervi Pantotrichum are that 0.1-10%, Sanguis Draxonis are that 0.1-10%, Pheretima are 0.1-10%.
Pharmaceutical composition preferred embodiment according to the present invention, wherein said pharmaceutical composition also contains one or more additional natural ingredients that are selected from following a group: Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Flos Carthami, Radix Aconiti Lateralis Preparata, Herba Asari, rhizoma sparganic, Rhizoma Curcumae, Fel Bovis seu Bubali, Semen Persicae.
Pharmaceutical composition preferred embodiment according to the present invention, the gross weight of wherein said medication composition accounts for the 10-40% of pharmaceutical composition gross weight, and each medication accounts for the 0.5-20% of total medication composition respectively.
According to a preferred embodiment of the invention, wherein also contain one or more pharmaceutically acceptable carrier or excipient.
Another object of the present invention provides the method for producing the pharmaceutical composition that is defined as above, this method comprises at first suitable part by weight, is ground into attritive powder through the mixture of Fel Ursi, Moschus, Calculus Bovis, Radix Ginseng, Radix Notoginseng, Squama Manis, Hirudo, Cornu Cervi Pantotrichum, Sanguis Draxonis and the Pheretima of concocting or not concocting; Prepare the water decoction of one or more medicines that are selected from Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Flos Carthami, Radix Aconiti Lateralis Preparata, Herba Asari, rhizoma sparganic, Rhizoma Curcumae, Fel Bovis seu Bubali, Semen Persicae then and be condensed into and soak paste; The powder of the last main ingredient that will as above obtain under strong agitation intersperses among in the extractum of the ancillary drug composition that as above obtains equably.
A preferred embodiment according to the inventive method; wherein the weight ratio of each main ingredient is: the content of Fel Ursi is 0.01-1%, and Moschus is that 0.01-1%, Calculus Bovis are that 0.01-1%, Radix Ginseng Rubra are that 0.1-10%, Radix Notoginseng are that 0.1-10%, Squama Manis are that 0.1-10%, Hirudo are that 0.1-10%, Cornu Cervi Pantotrichum are that 0.1-10%, Sanguis Draxonis are that 0.1-10%, Pheretima are 0.1-10%.
According to a preferred embodiment of the inventive method, the gross weight of said medication composition accounts for the 10-40% of pharmaceutical composition gross weight, and the content of each medication composition accounts for the 0.5-20% of total medication composition respectively.
A preferred embodiment according to the inventive method wherein also contains one or more pharmaceutically acceptable carrier or excipient.
A further object of the present invention provides the pharmaceutical composition that is defined as above is used for preventing or treating the medicine of cardiovascular and cerebrovascular vessel thrombosis and relevant disease in production application.
Purposes preferred embodiment according to the present invention, wherein said relevant disease comprises myocardial infarction, myocardial ischemia, cardiac arrhythmia, cerebral vessels embolism, numb limbs and tense tendons and hemiplegia.
The present invention relates to new pharmaceutical composition, particularly relate to and be used to prevent and control thrombotic new natural drug composition, its preparation method, and be used for preventing and treat the application of the medicine of thrombosis and relevant disease in production.
Pharmaceutical composition of the present invention is made up of main ingredient Fel Ursi, Moschus, Calculus Bovis, Radix Ginseng Rubra, Radix Notoginseng, Squama Manis, Hirudo, Cornu Cervi Pantotrichum, Sanguis Draxonis and Pheretima basically.Wherein the content according to the weight ratio Fel Ursi is 0.01-1%, and Moschus is that 0.01-1%, Calculus Bovis are that 0.01-1%, Radix Ginseng Rubra are that 0.1-10%, Radix Notoginseng are that 0.1-10%, Squama Manis are that 0.1-10%, Hirudo are that 0.1-10%, Cornu Cervi Pantotrichum are that 0.1-10%, Sanguis Draxonis are that 0.1-10%, Pheretima are 0.1-10%.Said pharmaceutical composition also contains one or more additional natural ingredients that are selected from following a group: Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Flos Carthami, Radix Aconiti Lateralis Preparata, Herba Asari, rhizoma sparganic, Rhizoma Curcumae, Fel Bovis seu Bubali, Semen Persicae.The gross weight of wherein said medication composition accounts for the 10-40% of pharmaceutical composition gross weight, and each medication accounts for the 0.5-20% of total medication composition respectively.
The inventor in conjunction with Chinese traditional medicine scientific principle opinion and modern pharmacology and clinical medicine experimental technique, designs and has prepared above-mentioned one group of new pharmaceutical composition in its long-term tcm clinical practice.Zoopery and clinic trial result show that pharmaceutical composition of the present invention can be used for prevention and treats the heart, cerebrovascular thrombosis, and comprise the multiple relevant disease of myocardial infarction, myocardial ischemia, cerebral vessels embolism, numb limbs and tense tendons and hemiplegia.
As everyone knows, Fel Ursi mainly contains ursodeoxycholic acid and chenodeoxy cholic acid, has excited heart clinically, lowers blood pressure and function of detoxification.Moschus is the dry secretions in the ripe male sachet of animal in deer family, contains compositions such as muscone, and has B-adrenergic receptor potentiation, can be used for treating angina pectoris and vascular headache.Calculus Bovis is the calculus in cattle or Babalus bubalis L. gallbladder or the bile duct, mainly contains bile acid and bilirubin, has the central excitation of alleviating and anti inflammatory detoxication effect.Contain multiple ginsenoside in the root of araliaceae ginseng plant's Radix Ginseng, known some ginsenoside has the activity of improving brain and coronary flow circulation, blood fat reducing and raising myocardial function at present.Radix Notoginseng also is the araliaceae ginseng plant, contains notoginseng saponin in its root and has the effect similar to the ginsenoside.Squama Manis is the scute of Manidae vertebrates anteater Manitis, is mainly used in the stimulating milk secretion of stimulating the menstrual flow, the routed pus of detumescence.Hirudo is the dry Scorpio of trematodiasis section animal Hirudo, contains the anticoagulative substance hirudin in its salivary gland, can be used for treating traumatic injury and neurodermatitis.Cornu Cervi Pantotrichum is Cervus nippon Temminck and the still unossified young horn of Cervus elaphus linnaeus, wherein contains several amino acids and phospholipid and hormonal substance, has blood vessel dilating, brings high blood pressure down, promotes effects such as wound healing.Sanguis Draxonis is the resin that oozes out in the plant kylin Sanguis Draxonis fruit, has anastalsis and is applied to treat traumatic injury and the promotion wound healing.Pheretima is the dry body of huge earthworm section animal Pheretima aspergillum, contains compositions such as lumbricin and terrestro-lumbrolysin, have bring high blood pressure down, calm, alleviate smooth muscle spasm and Detoxication.
In addition, pharmaceutical composition of the present invention also contains one or more additional natural ingredients that are selected from Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Flos Carthami, Radix Aconiti Lateralis Preparata, Herba Asari, rhizoma sparganic, Rhizoma Curcumae, Fel Bovis seu Bubali, Semen Persicae.The source of these natural medicinal ingredients, pharmaceutical active and effect also are well known by persons skilled in the art, perhaps can find from textbook.
Yet, use the said herbal medicine medicine as basic or ancillary drug composition, according to traditional Chinese medicine and pharmacy theory, and, make new pharmaceutical composition of the present invention in conjunction with modern pharmacology and clinic study method, be not report in the prior art.
Therefore; the invention provides with natural drug Fel Ursi, Moschus, Calculus Bovis, Radix Ginseng Rubra, Radix Notoginseng, Squama Manis, Hirudo, Cornu Cervi Pantotrichum, Sanguis Draxonis and Pheretima is the essential drugs composition, and is the new composition medicine of supplementary element with one or more medicines that are selected from Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Flos Carthami, Radix Aconiti Lateralis Preparata, Herba Asari, rhizoma sparganic, Rhizoma Curcumae, Fel Bovis seu Bubali, Semen Persicae.Wherein, the weight ratio of each main ingredient is: the content of Fel Ursi is 0.01-1%, and Moschus is that 0.01-1%, Calculus Bovis are that 0.01-1%, Radix Ginseng Rubra are that 0.1-10%, Radix Notoginseng are that 0.1-10%, Squama Manis are that 0.1-10%, Hirudo are that 0.1-10%, Cornu Cervi Pantotrichum are that 0.1-10%, Sanguis Draxonis are that 0.1-10%, Pheretima are 0.1-10%.And wherein the gross weight of medication composition accounts for the 10-40% of pharmaceutical composition gross weight, and the content of each medication composition accounts for the 0.5-20% of total medication composition respectively.In addition, remove above-mentioned effective ingredient, composition medicine of the present invention also contains one or more pharmaceutically acceptable carrier or excipient.
The present invention also provides the method for producing the pharmaceutical composition that is defined as above, and this method comprises:
(1) at first will be as the essential drugs composition, the mixture of Fel Ursi, Moschus, Calculus Bovis, Radix Ginseng Rubra, Radix Notoginseng, Squama Manis, Hirudo, Cornu Cervi Pantotrichum, Sanguis Draxonis and the Pheretima of the suitable part by weight that process is concocted or do not concocted is ground into attritive powder (granularity is less than or equal to 200 orders), and wherein the concocting method of Hirudo is: use pre-warmed siritch (vegetable oil) that Hirudo is fried in shallow oil and fry to coke yellow; The concocting method of Cornu Cervi Pantotrichum is: Cornu Cervi Pantotrichum is mixed the back heated 20 minutes down in 20 ℃ with isopyknic soft shelled turtle gallbladder; The concocting method of Sanguis Draxonis is: Sanguis Draxonis is added in isopyknic Sanguis cervi, stir following 60 ℃ of heating 15 minutes.
(2) then, after will mixing by suitable part by weight as one or more medicines that are selected from Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Flos Carthami, Radix Aconiti Lateralis Preparata, Herba Asari, rhizoma sparganic, Rhizoma Curcumae, Fel Bovis seu Bubali, Semen Persicae of auxiliary element, to the water that wherein adds 2-4 times of volume, soaked 8-24 hour under the room temperature.Soaked the back slowly heated and boiled 0.5-2 hour.Filter then and collect filtrate, and in medicinal residues, go into 1-3 times of volume water once more and continued to boil 0.5-2 hour, so repeat 2 times.Merge the filtrate that obtains after three heating decoct, concentrate down in decompression, until obtaining the thickness paste [about 30% (w/w) of water content] that to flow.
(3) last, in the fine powder of the essential drugs composition that under the strong agitation step (1) is made equably spreading in the extractum of the ancillary drug composition that step (2) makes.The viscosity of said concentrated extract with lucky parcel each independently powder particle be advisable.In some cases, need further pulverize the mixture that this step obtains behind the mixing, so that prepare the relative medicine of various different dosage forms.
Pharmaceutically acceptable carrier of pharmaceutical composition of the present invention and one or more or excipient can be mixed by proper proportion, make the medicine of the different dosage form that is suitable for clinical use.For example said compositions can be configured to supply the injection of intravenous, intramuscular, intraperitoneal, subcutaneous, Intradermal, the administration of marrowbrain intracavitary administration, perhaps make the tablet, powder agent, pill, capsule and the suspending agent that are suitable for oral administration.
In order to prepare the solution that is suitable for the outer administration of gastrointestinal tract, for example can use distilled water, water for injection, isotonic sodium chloride or glucose solution as carrier or excipient.Can be outside these gastrointestinal tract add one or more other auxiliary elements or additives in the preparation of administration, for example can use ascorbic acid as antioxidant, use sodium benzoate or methyl hydroxybenzoate as antiseptic, use dimethyl sulfoxide as absorption enhancer.
In order to prepare tablet, powder agent, pill, capsule and the suspending agent that is suitable for oral administration, can use sucrose, lactose, galactose, corn starch, gelatin, lipid, microcrystalline Cellulose, carboxymethyl cellulose, Pulvis Talci etc. as carrier or excipient.Be suitable for also can containing other proper additive in the preparation of oral administration, for example solubilizing agent, disintegrating agent, lubricant, absorption enhancer, dispersant, surfactant, sweeting agent, flavouring agent and coloring agent at these.
Preferably pharmaceutical composition of the present invention is made the various dosage forms that are suitable for oral administration, for example tablet, powder agent, capsule, oral liquid or Emulsion.The unit dose of these oral formulations generally comprises 100-500mg pharmaceutical composition of the present invention.When for example being used for the treatment of the ischemic cardio-cerebral diseases, the adult dosage of common 60 kg body weight is 1-10g every day, divides two to three administrations.Another preferred route of administering of this pharmaceutical composition is the injection that intravenous or intramuscular injection are suitable for these route of administration.For example for the patient of some acute myocardial infarction or the convalescent patient of cerebral embolism or the frequent outbreak of angina pectoris, the injection formulation of pharmaceutical composition of the present invention can be added in etc. and ooze in glucose solution or the isotonic sodium chlorrde solution, constantly dropleting medicine-feeding.The dosage of intravenous administration is generally 0.2-5g every day.
The present invention further provides said pharmaceutical composition and be used for the treatment of and prevent the heart, cerebrovascular thrombosis, and comprised application in the medicine of multiple relevant disease of myocardial infarction, myocardial ischemia, cerebral vessels embolism, numb limbs and tense tendons and hemiplegia in production.
General pharmacology is learned and pharmacodynamic experiment shows, pharmaceutical composition of the present invention comprises the activity and the not obviously influence of behavior of (mice, rat and dog) to animal.After per os gavaged pharmaceutical composition of the present invention (100mg/kg), the blood pressure of animal, heart rate and electrocardiogram were all normal substantially.The pharmacodynamic study result shows, pharmaceutical composition of the present invention has significant protective effect to the rat heart muscle ischemia that experimental myocardial infarction and isoproterenol bring out.For example, exempt from intravenous injection pharmaceutical composition of the present invention for experimental myocardial infarction man after, can alleviate the Electrocardiographic ischemic change of front multi-lead significantly.The p-isopropyl epinephrine brings out the rat of myocardial ischemia behind intragastric infusion pharmaceutical composition of the present invention (100mg/kg); as seen serum paraoxonase creatine phosphate kinase (CPK) of animal and lactic acid dehydrogenase (LDH) are active reduces, thereby infers that pharmaceutical composition of the present invention may be relevant with free-fat and lipid peroxide in its reduction ischemic myocardial tissue to the protective effect of myocardial damage.
In addition, we have also observed pharmaceutical composition of the present invention to the coronary artery circulation of laboratory animal and the influence of myocardium oxygen metabolism.The result shows that pharmaceutical composition of the present invention can increase the blood flow of animal cardiac muscle significantly and reduce coronary resistance.Though see said composition the coefficient of oxygen utilization of cardiac muscle is not had a significant effect, find that it can reduce myocardial oxygen consumption and myocardial oxygen consumption index significantly.
The following example is intended to further describe for example the present invention, rather than limits the await the reply scope of claim of the present invention by any way.
Embodiment 1: preparation of drug combination of the present invention
This enforcement is example with the hard capsule, and the method for preparing pharmaceutical composition of the present invention is described, wherein given dosage percentage ratio is weight ratio.
(1) takes by weighing natural drug Radix Angelicae Sinensis 2000g, Radix Salviae Miltiorrhizae 2500g, Flos Carthami 1500g, Radix Aconiti Lateralis Preparata 1500g, Herba Asari 1000g, rhizoma sparganic 2000g, Rhizoma Curcumae 1000g, Semen Persicae 1500g and limacia sagittata 1500g respectively, to the water that wherein adds 2 times of volumes, place soaked overnight under the room temperature behind the mixing.Next day, said medicine was placed on the slow fire heated and boiled 40 minutes.Filter decoction liquor and collect filtrate with filter cloth then.The water that in medicinal residues, adds 2 times of volumes once more, and heated and boiled 40 minutes, repetitive operation secondary like this, and filter respectively and collect filtrate.The filtrate that merges three decoctions, and under decompression, be concentrated into 20% of original volume according to a conventional method, obtain flowable thickness paste.
(2) take by weighing 2 of Fel Ursis (about 30g) respectively; behind Moschus 10g, Calculus Bovis 30g, Radix Ginseng Rubra 5000g, Radix Notoginseng 5000g, Squama Manis 4000g, Hirudo 3000g, Cornu Cervi Pantotrichum 2000g, Sanguis Draxonis 3000g and the Pheretima 3000g mixing, use mechanical lapping equipment degree of being ground into to be equal to or less than 200 purpose attritive powders.Perhaps, for fear of losing of valuable medicinal Moschus, Fel Ursi and Calculus Bovis, also can in advance these three kinds of medical materials be developed powder separately.
(3) under high-speed stirred, the powder of the essential drugs composition that makes in the step (2) slowly and equably is spread in the concentrated extract of the ancillary drug composition that makes in the step (1), obtain the fine particulate thing of brown partial desiccation state.
(4) further will as above obtain be wrapped after the fine particulate thing air-dry after, pack in the hard capsules by the amount branch of every capsule 500mg.
Embodiment 2: the influence of the inductive mice general of pharmaceutical composition p-isopropyl epinephrine of the present invention anoxia tolerance
The male mice of 50 about 19-21 grams of body weight is divided into 5 groups, 10 every group at random.Two experimental grouies per os respectively gavage pharmaceutical composition 100 of the present invention and 200mg/kg body weight.The blank group gavages equal-volume (2ml) normal saline; Two treatment matched groups gavage commercially available BUCHANG NAOXINTONG 100mg/kg body weight respectively simultaneously.After 15 minutes, except that the blank group, all the other are the equal subcutaneous injection isoproterenol of animal 20mg/kg body weight of group respectively after the administration.Through 15 minutes, each treated animal is put into the airtight wide mouthed bottle of 250ml that sodica calx (10g) is housed respectively in the same time again, observe and write down the time-to-live of animal at once.The result is with myocardial infarction area (mm
2) or the mean+SD of sero-enzyme concentration (units per liter) represent (n=8～10).Shown in the following tabulation 1 of result.
Table 1 pharmaceutical composition of the present invention is to the anoxybiotic influence of the inductive rat body of isoproterenol
Group dosage (mg/kg) time-to-live (minute) survival rate
Negative control group-46.5 ± 2.0
*5/10
Isoproterenol processed group 20 28.3 ± 2.6 0/10
Pharmaceutical composition 100 32.1 of the present invention ± 4.8 3/10
Pharmaceutical composition 200 46.5 ± 6.0 of the present invention
*6/10
BUCHANG NAOXINTONG group 10 36.8 ± 5.2
*5/10
*Compare with the isoproterenol group: P＜0.01
As can be seen, the subcutaneous injection isoproterenol can significantly shorten the time-to-live of mice under the normobaric hypoxia environment from last tabulation 1, compares with the negative control group of an injecting normal saline, and difference is (P＜0.01) especially significantly.Injection pharmaceutical composition 100 of the present invention or 200mg/kg body weight in the mice body in advance, can resist effectively continue after the animal general anaerobic condition that causes of subcutaneous injection isoproterenol, thereby prolong the time-to-live of animal under the normobaric hypoxia environment greatly.Compare with the matched group that gavages BUCHANG NAOXINTONG (100mg/kg body weight) in advance, its effect is more obvious.
Embodiment 3: pharmaceutical composition of the present invention to the impatient property of rat experiment core ischemia after the influence that changes of electrocardiogram
Each 20 of the male and female Wistar rats of the about 105g of average weight are divided into 4 groups, 10 every group at random.Two experimental grouies per os respectively gavage pharmaceutical composition of the present invention (100,200mg/kg body weight).Negative control group gavages isopyknic normal saline.The positive controls per os gavages commercially available BUCHANG NAOXINTONG (100mg/kg).After 5 minutes, each treated animal is intravenous injection pituitrin (biochemical-pharmaceutical factory, Shenyang) (1 unit/kg), and inject in the kind in 10 seconds with constant speed and to finish respectively.Behind injection of pituitrin, traced the electrocardiogram of animal in 10,20,40,60 minutes.Under tabulate and shown behind the intravenous injection pituitrin that 20 minutes Electrocardiographic ST sections of animal and T ripple change in 2.The result represents (n=10) with the mean+SD of electrocardio millivolt (mV) number.
The Electrocardiographic influence of acute myocardial ischemia rat that table 2 pharmaceutical composition of the present invention brings out pituitrin
Group ST section (mV) T ripple (mV)
Negative control group 0.20 ± 0.02 0.30 ± 0.086
BUCHANG NAOXINTONG 0.02 ± 0.01
* *0.06 ± 0.04
* *
Experimental group
100mg/kg 0.08±0.03
** 0.11±0.02
**
200mg/kg 0.05±0.02
*** 0.10±0.04
**
Compare with matched group:
*P＜0.05,
*P＜0.01,
* *P＜0.001
From the result shown in the table 2 as can be seen, to animal come into operation can obviously suppress behind the medicine of the present invention continue after the pituitrin Acute Myocardial Ischemia in Rats ECG change (the ST section is raised with the T wave height and alarmmed) of bringing out.After promptly per os gavages pharmaceutical composition of the present invention in advance, can suppress the acute coronary vasospasm that vasoconstrictor causes effectively, and then alleviate acute myocardial ischemia.In addition, behind the experimental group animal-use drug, but disappear after being also shown in the characteristic pathology Q ripple Yu Santian of myocardium thromboembolism.
Embodiment 4: the clinical trial result of pharmaceutical composition of the present invention is observed
In order further to confirm the result of use of pharmaceutical composition of the present invention in prevention and treatment thrombosis and relevant cerebrovascular disease.The inventor is under proving that through toxicological experiment this pharmaceutical composition is without any acute and chronic toxic prerequisite, obtain patient and family members' thereof agreement, acute or chronic thromboembolism and the relevant cerebrovascular patient who has made a definite diagnosis carried out clinic trial and effect observation.
214 examples are comprised the patient of cerebral thrombosis, cerebral embolism, hemiplegia, hemiplegia complicated hypertension be divided into treatment group and experimental group at random, be respectively 123 example and 91 examples.Wherein treatment group male patient 72 examples, female patients 51 examples, and patient's mean age be 58.5 years old.Matched group patient male 51 examples, female patients 40 examples, and patient's mean age be 57 years old.All cases all are diagnosed as above-mentioned disease at city-level with the image analysises such as manager inspection, hematology and biochemical test and electrocardiogram, rheoencephalogram, CT of going to the hospital.
Antithrombotic that positive controls venous patient infusion is commercially available and sequela medicine MAILUONING (Nanjing Jinling Pharmaceutical Factory) 20mg+10% glucose injection 250ml, or ligustrazine (Wuxi the 7th pharmaceutical factory) 80mg+10% glucose injection 250ml, once a day.The oral pharmaceutical composition of the present invention of experimental group patient is taken medicine 2 every day, each 3g.Two groups of patient's continuous uses were observed and the record therapeutic effect after 20 days.Curative effect judging standard: patient's subjective symptom (obviously go down, consciousness and language function obstacle, swallow and the dysfunction of taking food) complete obiteration as disorder of limb ' s activity, memory; The all normal person of physical and chemical indexs such as blood fat, blood viscosity and blood pressure is regarded as recovery from illness.Patient's above-mentioned subjective symptom partly disappears or alleviates; Physical and chemical indexs such as blood fat, blood viscosity and blood pressure are improvement trend person and are regarded as treatment effectively.Shown in the following tabulation 3 of result.Wherein cure rate and effective percentage are all represented with the percent that accounts for the total inspection case load, and total effective rate is cure rate and effective percentage sum.
Table 3: the clinic trial observed result of pharmaceutical composition of the present invention
Group example number cure rate effective percentage total effective rate
Experimental group 123 examples 85.4% 13% 98.4%
Matched group 91 examples 39.6% 25.2% 64.8%
From result shown in the table 3 as can be seen, pharmaceutical composition of the present invention can be treated diseases such as cerebral thrombosis, cerebral infarction, hemiplegia or hemiplegia accompanied with hypertension effectively.To the nearly 2 years tracking Follow-up results of above-mentioned these patients as seen, patient's muscle power, quality of life and self care ability all have clear improvement.
Claims (10)
1, a kind of new pharmaceutical composition is characterised in that what said pharmaceutical composition was made up of Fel Ursi, Moschus, Calculus Bovis, Radix Ginseng Rubra, Radix Notoginseng, Squama Manis, Hirudo, Cornu Cervi Pantotrichum, Sanguis Draxonis and the Pheretima of the main ingredient of conduct basically.
2, according to the pharmaceutical composition of claim 1; wherein the content according to the weight ratio Fel Ursi is 0.01-1%, and Moschus is that 0.01-1%, Calculus Bovis are that 0.01-1%, Radix Ginseng Rubra are that 0.1-10%, Radix Notoginseng are that 0.1-10%, Squama Manis are that 0.1-10%, Hirudo are that 0.1-10%, Cornu Cervi Pantotrichum are that 0.1-10%, Sanguis Draxonis are that 0.1-10%, Pheretima are 0.1-10%.
3, according to the pharmaceutical composition of claim 1, wherein said pharmaceutical composition also contains one or more additional natural ingredients that are selected from following a group: Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Flos Carthami, Radix Aconiti Lateralis Preparata, Herba Asari, rhizoma sparganic, Rhizoma Curcumae, Fel Bovis seu Bubali, Semen Persicae.
4, according to the pharmaceutical composition of claim 1, the gross weight of wherein said medication composition accounts for the 10-40% of pharmaceutical composition gross weight, and each medication accounts for the 0.5-20% of total medication composition respectively.
5, according to the pharmaceutical composition of claim 1, wherein also contain one or more pharmaceutically acceptable carrier or excipient.
6, produce the method for the pharmaceutical composition that is defined as above, this method comprises at first suitable part by weight, is ground into attritive powder through the mixture of Fel Ursi, Moschus, Calculus Bovis, Radix Ginseng, Radix Notoginseng, Squama Manis, Hirudo, Cornu Cervi Pantotrichum, Sanguis Draxonis and the Pheretima of concocting or not concocting; Prepare the water decoction of one or more medicines that are selected from Radix Angelicae Sinensis, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae, Flos Carthami, Radix Aconiti Lateralis Preparata, Herba Asari, rhizoma sparganic, Rhizoma Curcumae, Fel Bovis seu Bubali, Semen Persicae then and be condensed into and soak paste; The powder of the last main ingredient that will as above obtain under strong agitation intersperses among in the extractum of the ancillary drug composition that as above obtains equably.
7, according to the method for claim 6; wherein the weight ratio of each main ingredient is: the content of Fel Ursi is 0.01-1%, and Moschus is that 0.01-1%, Calculus Bovis are that 0.01-1%, Radix Ginseng Rubra are that 0.1-10%, Radix Notoginseng are that 0.1-10%, Squama Manis are that 0.1-10%, Hirudo are that 0.1-10%, Cornu Cervi Pantotrichum are that 0.1-10%, Sanguis Draxonis are that 0.1-10%, Pheretima are 0.1-10%.
8, according to the method for claim 6, the gross weight of said medication composition accounts for the 10-40% of pharmaceutical composition gross weight, and the content of each medication composition accounts for the 0.5-20% of total medication composition respectively.
9, be used for preventing or treating the application of the medicine of cardiovascular and cerebrovascular vessel thrombosis and relevant disease in production according to the pharmaceutical composition of any one among the right 1--5.
10, according to the application of claim 10, wherein said relevant disease comprises myocardial infarction, myocardial ischemia, cardiac arrhythmia, cerebral vessels embolism, numb limbs and tense tendons and hemiplegia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02116467 CN1202842C (en) | 2002-04-09 | 2002-04-09 | Medicine composition for preventing and treating thrombosis and relative disease |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02116467 CN1202842C (en) | 2002-04-09 | 2002-04-09 | Medicine composition for preventing and treating thrombosis and relative disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1449775A true CN1449775A (en) | 2003-10-22 |
| CN1202842C CN1202842C (en) | 2005-05-25 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02116467 Expired - Lifetime CN1202842C (en) | 2002-04-09 | 2002-04-09 | Medicine composition for preventing and treating thrombosis and relative disease |
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| Country | Link |
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| CN (1) | CN1202842C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100339091C (en) * | 2005-04-08 | 2007-09-26 | 周宜轩 | Preparation of pharmaceutical composition for treating coronary heart disease and angina pectoris and preparation method thereof |
| CN101797330A (en) * | 2010-04-09 | 2010-08-11 | 朱明军 | Lipid regulating and meridians activating capsule |
| CN104324325A (en) * | 2014-10-30 | 2015-02-04 | 梁春林 | Traditional Chinese medicine composition for dredging vessels and dissolving thrombosis and preparation method thereof |
-
2002
- 2002-04-09 CN CN 02116467 patent/CN1202842C/en not_active Expired - Lifetime
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100339091C (en) * | 2005-04-08 | 2007-09-26 | 周宜轩 | Preparation of pharmaceutical composition for treating coronary heart disease and angina pectoris and preparation method thereof |
| CN101797330A (en) * | 2010-04-09 | 2010-08-11 | 朱明军 | Lipid regulating and meridians activating capsule |
| CN101797330B (en) * | 2010-04-09 | 2011-06-01 | 朱明军 | Lipid regulating and meridians activating capsule |
| CN104324325A (en) * | 2014-10-30 | 2015-02-04 | 梁春林 | Traditional Chinese medicine composition for dredging vessels and dissolving thrombosis and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1202842C (en) | 2005-05-25 |
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