CN1122717A - Improved thrombin compound - Google Patents

Improved thrombin compound Download PDF

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Publication number
CN1122717A
CN1122717A CN 95103018 CN95103018A CN1122717A CN 1122717 A CN1122717 A CN 1122717A CN 95103018 CN95103018 CN 95103018 CN 95103018 A CN95103018 A CN 95103018A CN 1122717 A CN1122717 A CN 1122717A
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China
Prior art keywords
thrombin
units
aminoacid
sugar alcohol
amino acids
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Pending
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CN 95103018
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Chinese (zh)
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迟斌元
司华
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Individual
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Individual
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Publication date
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Priority to CN 95103018 priority Critical patent/CN1122717A/en
Publication of CN1122717A publication Critical patent/CN1122717A/en
Pending legal-status Critical Current

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

The modified thrombin compound uses sugar alcohol or amino acids as additives. Owing to the addition of sugar alcohol or amino acids, the activity and the stability of the thrombin are strengthened and the solubility is also improved.

Description

A kind of improved thrombin compound
The invention relates to sugar alcohol, or the amino acids material is made a kind of improved thrombin compound as the additive of preparation thrombin.After its characteristics are to add these materials, protected the activity of thrombin, strengthened the stability of principal agent, the sample dissolution situation significantly improves.
Thrombin plays a crucial role in blood coagulation reaction as prothrombin a, and it directly acts on the final tache of coagulation process, make the Fibrinogen of solubility be transformed into insoluble fibrin, form blood clot, stop up the petechia, and reach the hemostatic purpose.In view of the above, before half a century, just there is the people that thrombin separation and Extraction from blood is come out,, is applied to the hemorrhage hemostasis of little blood vessel, blood capillary and parenchymal viscera of hemostasis by ligation difficulty as the local hemostasis medication.Up till now, the thrombin product is most not to add any additive for it extracts the direct dried frozen aquatic products of medicinal liquid, and the dried frozen aquatic products light weight is used for the petechia easily by the blood flow washout, affects the treatment, and dissolves in water slowly because of not having any hydrotropy material, sample, uses inconvenience.For this reason, have producer to extract at it abroad and add albumin or sucrose in medicinal liquid as the lyophilizing proppant, but albumin is as proppant, requirement is big, costs an arm and a leg, and be not suitable for producing in enormous quantities, and the protein matter hygroscopicity is strong, and it is fast to cause thrombin activity to reduce.The compositions that contains sucrose has bibulous shortcoming equally.
The purpose of this invention is to provide additive more suitable in the thrombin preparation process, protect its activity, strengthen the stability of principal agent, quicken the dissolving of dried frozen aquatic products in water, make a kind of improved thrombin compound.
This improved thrombin compound of the present invention is made up of thrombin and sugar alcohol, thrombin and amino acids material.The sugar alcohols material comprises mannitol, sorbitol, xylitol, maltose alcohol etc., preferred mannitol, sorbitol.The amino acids material comprises glycine, methionine, glutamic acid, leucine, arginine, cysteine etc., preferred glycine, methionine.Thrombin is thrombin with the ratio that cooperates of sugar alcohols material: sugar alcohol=1000 units: 0.5-3.0g is preferably 1000 units: 1.0-2.0g; Thrombin and amino acid ligand composition and division in a proportion example are thrombin: aminoacid=1000 units: 0.5-2.0g is preferably 1000 units: 1.0-1.5g.Preparation process is: the 1st kind of method, press thrombin in thrombin extraction medicinal liquid: sugar alcohol=1000 units: 0.5-3.0g, add sugar alcohol, or press thrombin: aminoacid=1000 units: 0.5-2.0g adds aminoacid, through degerming processing, lyophilizing promptly.The 2nd kind of method, get thrombin powder by thrombin: sugar alcohol=1000 units: 0.5-3.0g adds the sugar alcohol mixing, or press thrombin: aminoacid=1000 units: 0.5-2.0g adds the aminoacid mixing and sterilizes promptly.This improved compositions is measured its activity no change before and after lyophilizing and mixing by the method for pharmacopeia regulation, and compositions is difficult for moisture absorption, very easily is dissolved in the water.And show by accelerated test, contain this improved thrombin compound of 100 units at first and under 40 ℃ of relative humidity 75% conditions, placed three months that active nothing subtracts; And do not contain any additive or with sucrose be the thrombin compound of additive under similarity condition, the about 20-30% of loss of activity, concrete determination data sees Table 1.
Table 1
Storage requirement Sample Place three months activity change
January February March
40 ℃ of relative humiditys 75% of temperature Thrombin 100u ?90u ?83u ?72u
Thrombin+sucrose 100u: 0.1g ?95u ?85u ?78u
Thrombin+mannitol 100u: 0.15g ?102u ?98u ?99u
Thrombin+glycine 100u: 0.1g ?99u ?101u ?97u
Thrombin+sorbitol 100u: 0.1g ?97u ?98u ?99u
Thrombin+methionine 100u: 0.08g ?95u ?100u ?97u
Describe the foregoing of this discovery in detail below by concrete preferred example:
Embodiment one:
Get thrombin medicinal liquid 10ml (containing thrombin 1000 units), add mannitol 1.5g, after stirring makes it dissolving, handle through degerming, pharmaceutical composition is made in lyophilization.Determining thrombin activity by the pharmacopeia prescriptive procedure is 985 units, (the thrombin activity assay resultant error allows in 10%, and this result is in the evaluated error scope), and sample very easily is dissolved in water.
Embodiment two:
Get thrombin powder 0.5g (containing thrombin 2000 units), add sorbitol 1.0g mixing, sterilization promptly.Recording thrombin activity by the pharmacopeia prescriptive procedure is 2100 units.Sample very easily is dissolved in water.
Embodiment three:
Get thrombin medicinal liquid 10ml (containing thrombin 1000 units), add glycine 1.0g, after stirring makes it dissolving, handle through degerming, pharmaceutical composition is made in lyophilization.Recording thrombin activity by the pharmacopeia prescriptive procedure is 1050 units.Sample very easily is dissolved in water.
Embodiment four:
Get thrombin powder 0.5g (containing thrombin 2000 units), add methionine 0.8g mixing, sterilization promptly.Recording thrombin activity by the pharmacopeia prescriptive procedure is 1890 units.Sample very easily is dissolved in water.

Claims (6)

1. improved thrombin compound, said composition contain sugar alcohols or amino acids material as additive.
2. according to the compositions of claim 1: the sugar alcohols additive comprises mannitol, sorbitol, xylitol, maltose alcohol etc.; The amino acids additive comprises glycine, methionine, glutamic acid, leucine, cysteine, arginine etc.
3. according to the compositions of claim 1: the preferred mannitol of sugar alcohols additive, sorbitol; The preferred glycine of amino acids additive, methionine.
4. according to the compositions of claim 1: thrombin with the ratio that cooperates of sugar alcohols is in the said composition: thrombin: sugar alcohol=1000 units: 0.5-3.0g; Thrombin cooperates ratio to be with amino acids: thrombin: aminoacid=1000 units: 0.5-2.0g.
5. the preparation of compositions method according to claim 1 is: extract at thrombin and press thrombin in the medicinal liquid: sugar alcohol=1000 units: 0.5-3.0g, add sugar alcohol, or press thrombin: aminoacid=1000 units: 0.5-2.0g adds aminoacid, through degerming processing, lyophilizing promptly.
6. the preparation of compositions method according to claim 1 is: get thrombin powder by thrombin: sugar alcohol=1000 units: 0.5-3.0g adds the sugar alcohol mixing, or press thrombin: aminoacid=1000 units: 0.5-2.0g adds the aminoacid mixing, sterilizes promptly.
CN 95103018 1995-04-05 1995-04-05 Improved thrombin compound Pending CN1122717A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN 95103018 CN1122717A (en) 1995-04-05 1995-04-05 Improved thrombin compound

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN 95103018 CN1122717A (en) 1995-04-05 1995-04-05 Improved thrombin compound

Publications (1)

Publication Number Publication Date
CN1122717A true CN1122717A (en) 1996-05-22

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CN 95103018 Pending CN1122717A (en) 1995-04-05 1995-04-05 Improved thrombin compound

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CN (1) CN1122717A (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101137902B (en) * 2005-03-17 2012-04-18 积水化学工业株式会社 Blood coagulation accelerator and vessel for blood test
CN105181978A (en) * 2015-09-23 2015-12-23 青岛古高生物科技有限公司 Thrombin time measuring reagent and preparing method thereof
CN106350500A (en) * 2016-09-30 2017-01-25 四川迈克生物科技股份有限公司 Thrombin solution
CN106350501A (en) * 2016-09-30 2017-01-25 四川迈克生物科技股份有限公司 Stabilizer of thrombin solution
CN106480007A (en) * 2016-09-30 2017-03-08 四川迈克生物科技股份有限公司 The stabilizer of thrombin solution
WO2021063392A1 (en) * 2019-09-30 2021-04-08 积水医疗科技(苏州)有限公司 Thrombin solution, kit, stabilization method for thrombin, detection reagent, measurement method of thrombin time, and use of defoamer

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101137902B (en) * 2005-03-17 2012-04-18 积水化学工业株式会社 Blood coagulation accelerator and vessel for blood test
CN105181978A (en) * 2015-09-23 2015-12-23 青岛古高生物科技有限公司 Thrombin time measuring reagent and preparing method thereof
CN105181978B (en) * 2015-09-23 2016-07-20 青岛古高生物科技有限公司 A kind of thrombin time test reagent and preparation method thereof
CN106350500A (en) * 2016-09-30 2017-01-25 四川迈克生物科技股份有限公司 Thrombin solution
CN106350501A (en) * 2016-09-30 2017-01-25 四川迈克生物科技股份有限公司 Stabilizer of thrombin solution
CN106480007A (en) * 2016-09-30 2017-03-08 四川迈克生物科技股份有限公司 The stabilizer of thrombin solution
CN106480007B (en) * 2016-09-30 2018-02-23 迈克生物股份有限公司 The stabilizer of thrombin solution
CN106350500B (en) * 2016-09-30 2018-02-23 迈克生物股份有限公司 Thrombin solution
CN106350501B (en) * 2016-09-30 2018-06-01 迈克生物股份有限公司 The stabilizer of thrombin solution
WO2021063392A1 (en) * 2019-09-30 2021-04-08 积水医疗科技(苏州)有限公司 Thrombin solution, kit, stabilization method for thrombin, detection reagent, measurement method of thrombin time, and use of defoamer

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