CN1461655A - Thrombolytics enzyme contg. venin for injection - Google Patents
Thrombolytics enzyme contg. venin for injection Download PDFInfo
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- CN1461655A CN1461655A CN 02109872 CN02109872A CN1461655A CN 1461655 A CN1461655 A CN 1461655A CN 02109872 CN02109872 CN 02109872 CN 02109872 A CN02109872 A CN 02109872A CN 1461655 A CN1461655 A CN 1461655A
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- injection
- batroxobin
- fibrinolysin
- venin
- enzyme
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
A venin-thrombolytic enzyme in the form of injection for treating acute or recovery-stage cerebral thrombus and preventing thrombosis is prepared from the thrombin-like enzyme and the fibrinolytic enzyme, which are extracted from venin, through mixing in ratio of (2-5):(0.5-2.5). Its advantages are high purity, high curative effect and quickly taking its effect.
Description
Technical field the present invention relates to a kind of pharmaceutical products, particularly a kind of venin for injection streptokinase.
The medicine that background technology is treated thrombotic disease at present is a lot, but not ideal, as the Defibrase preparation of separating from snake venom of extensive use, its composition is pure batroxobin (Thrombin-like enzyme), because determined curative effect has become one of choice drug of treatment thrombotic disease.But because Defibrase is one-component-batroxobin (Thrombin-like), it mainly acts on the Fibrinogen among the human thrombus, only plays thrombolytic effect, and its drug effect is single.Ahylysantinfarctase is then good than Defibrase at the convalescent care to blood viscosity lowering and thrombosis patient, but because Ahylysantinfarctase is multi-component mixture, the component content that is used for the treatment of thrombotic disease is few, the effect of treatment thrombotic disease is remarkable inadequately, it has certain toxic and side effects simultaneously, has therefore suffered eliminating of Ministry of Public Health.
Summary of the invention the object of the present invention is to provide a kind of venin for injection streptokinase that preventive effect is good, onset rapid, have no side effect for the treatment of.
The present invention is the curative effect that integrates Defibrase and Ahylysantinfarctase, and it is at treatment and prevention thrombotic disease and blood viscosity lowering, falls the blood ester, reduces Fibrinogen and prevents that from all there is good effect aspect such as hematoblastic gathering.Technology solution of the present invention is to extract batroxobin (Thrombin-like enzyme) and two components of fibrinolysin (Fibrinolytic enzyme) from snake venom, and batroxobin and fibrinolysin by the vigor ratio are 2～5: 0.5～2.5 mixed.Batroxobin is preferably 3～4.5: 0.5～2 with the vigor ratio of fibrinolysin.Every injection should contain 4～5 total activity units.Above-mentioned batroxobin and fibrinolysin are to extract from agkistrodon halyx pallas venom, and its purity is higher than 90% respectively.
In order to increase stability of drug, when the system lyophilized injectable powder, can be before lyophilizing add 1% dextran in every milliliter of medicinal liquid, make lyophilized injectable powder through lyophilization then.When the controlling the water circulation injection, should add an amount of stabilizing agent (chlorobutanol) and protective agent (gelatin hydrolysied matter) in the injection.
From Pallas pit viper poisonous snake poison extraction batroxobin and fibrinolysin process be:
1, sieve chromatography
Snake venom is dissolved in the Tris-HCl buffer, is splined on the prior 10mM 0 of using, the equilibrated Sephacryl S-200 of the Tris-HCl buffer HR gel of 15M is used the level pad eluting, collects activated batroxobin and fibrinolysin respectively.
2, ion-exchange chromatography
Activated batroxobin that will obtain from step 1 and fibrinolysin respectively through distill water dialysis, concentrate, go up in advance with the equilibrated DEAE-Sepharose FF of 0.02M Tris-HCl buffer gel, use the balance liquid eluting then, collecting respectively has active part.
3, affinity chromatograph
Activated batroxobin that obtains from step 2 and fibrinolysin are respectively to distill water dialysis, concentrate, go up and use 50mM Tris-HCl-NaCl-0 in advance, the equilibrated Benzamidine-Sepharose 6B of 5M gel, with the Tris-HCl buffer solution elution that contains NaCl, collection has active part, obtains purity respectively and be batroxobin and fibrinolysin more than 90%.
The pharmacological action of above-mentioned two components is as follows:
Batroxobin mainly is to act on Fibrinogen in the blood in vivo, fibrinogen content is reduced, thereby play thrombolytic effect.Increase with platelet aggregation and cause because the formation of thrombosis mainly is Fibrinogen.One of main component of thrombosis is a Fibrinogen, and batroxobin in vivo can the former grumeleuse of solution fibrin, thereby makes the blood circulation in the blood vessel, has treated thrombotic disease.
Fibrinolysin also is a component in the snake venom, has the fibrinogenic effect that directly acts in blood.The model of action of fibrinolysin has two kinds: the one, similar plasmin-like effect is arranged, and directly solution fibrin is former and change the stability of plasma fibrinogen, removes the Fibrinogen monomer from blood plasma, and then plays thrombolytic effect; The 2nd, by the activation plasmin, play fibrinolysis.The two has synergism batroxobin and fibrinolysin, and curative effect heightens.
Preliminary test shows: preparation of the present invention has that thrombus dissolving is effective, effect is rapider, and the generation of thrombosis later stage old thrombosis and pre-preventing thrombosis is all had significant effect.The component purity height of preparation does not contain kallikrein, does not contain other residual in snake venom separation process composition yet.Have the function that reduces plasma fibrinogen, blood viscosity and platelet aggregation, thereby anticoagulation is arranged.Be specially adapted to treatment acute and the convalescent period cerebral embolism, and the formation of prevention thrombotic disease.
The specific embodiment:
Example 1: by above-mentioned processing step from snake venom respectively dna purity be that 92% batroxobin and purity are 90% fibrinolysin, the injection of preparation 1000ml, its contained batroxobin is 8000u, fibrinolysin is 2000u, and the dextran of adding 100g, through aseptic filtration, get 0.5ml and be divided in the 2ml injection peace bottle, frozen drying, seal.
Example 2: dna purity is that 94% batroxobin and purity are 93% fibrinolysin respectively from snake venom, the injection of preparation 1000ml, contained batroxobin 9000u, fibrinolysin 1000u, add Dextran 10 0g, through aseptic filtration, get 0.5ml and be divided in the 2ml injection peace bottle, frozen drying, seal.
Example 3: dna purity is that 93% batroxobin and purity are 96% fibrinolysin respectively from snake venom, the injection of preparation 1000ml, and contained batroxobin 3500u, fibrinolysin 1500u add chlorobutanol 1.5g, gelatin hydrolysied matter 50mg.Get 1ml and pack in the 2ml peace bottle, seal.
Example 4: dna purity is that 95% batroxobin and purity are 97% fibrinolysin respectively from snake venom, the injection of preparation 1000ml, and contained batroxobin 3000u, fibrinolysin 1500u add chlorobutanol 1.5g, gelatin hydrolysied matter 50mg.Get 1ml and pack in the 2ml peace bottle, seal.
Example 5: dna purity is that 97% batroxobin and purity are 97% fibrinolysin respectively from snake venom, the injection of preparation 1000ml, and contained batroxobin 3000u, fibrinolysin 1500u add chlorobutanol 1.5g, gelatin hydrolysied matter 50mg.Get 1ml and pack in the 2ml peace bottle, seal.
Claims (5)
1, a kind of venin for injection streptokinase, it is characterized in that the streptokinase that extracts is made up of batroxobin (Thrombm-like enzyme) and two components of fibrinolysin (Fibrinolytic enzyme) from snake venom, and batroxobin and fibrinolysin by the vigor ratio are 2～5: 0.5～2.5 mixed preparation.
2, venin for injection streptokinase according to claim 1 is characterized in that the batroxobin and the vigor ratio of fibrinolysin are 3～4.5: 0.5～2.
3, venin for injection streptokinase according to claim 1 is characterized in that every injection contains 4～5 units of total activity.
4,, it is characterized in that the batroxobin that extracts and the purity of fibrinolysin are higher than 90% respectively from snake venom according to claim 1,2 described venin for injection streptokinases.
5, according to claim 1,2 described venin for injection streptokinases, described batroxobin and the fibrinolysin that it is characterized in that are to extract from agkistrodon halyx pallas venom.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02109872 CN1461655A (en) | 2002-05-27 | 2002-05-27 | Thrombolytics enzyme contg. venin for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02109872 CN1461655A (en) | 2002-05-27 | 2002-05-27 | Thrombolytics enzyme contg. venin for injection |
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| Publication Number | Publication Date |
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| CN1461655A true CN1461655A (en) | 2003-12-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN 02109872 Pending CN1461655A (en) | 2002-05-27 | 2002-05-27 | Thrombolytics enzyme contg. venin for injection |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100355885C (en) * | 2006-01-18 | 2007-12-19 | 齐鲁制药有限公司 | Method for extracting single ingredient defibrase from snake venom |
| CN110016471A (en) * | 2019-04-10 | 2019-07-16 | 北京博康宁生物医药科技有限公司 | Recombinant ancrod enzyme and commercial scale preparation and purification method and combinations thereof |
-
2002
- 2002-05-27 CN CN 02109872 patent/CN1461655A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100355885C (en) * | 2006-01-18 | 2007-12-19 | 齐鲁制药有限公司 | Method for extracting single ingredient defibrase from snake venom |
| CN110016471A (en) * | 2019-04-10 | 2019-07-16 | 北京博康宁生物医药科技有限公司 | Recombinant ancrod enzyme and commercial scale preparation and purification method and combinations thereof |
| CN110016471B (en) * | 2019-04-10 | 2020-10-02 | 北京博康宁生物医药科技有限公司 | Recombinant ancrod enzyme, industrial scale preparation and purification method and composition thereof |
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