CN102258770A - Safe and efficient lyophilized fibrin sealant (FS) and preparation method thereof - Google Patents
Safe and efficient lyophilized fibrin sealant (FS) and preparation method thereof Download PDFInfo
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- CN102258770A CN102258770A CN2010101829682A CN201010182968A CN102258770A CN 102258770 A CN102258770 A CN 102258770A CN 2010101829682 A CN2010101829682 A CN 2010101829682A CN 201010182968 A CN201010182968 A CN 201010182968A CN 102258770 A CN102258770 A CN 102258770A
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Abstract
The invention discloses a safe and efficient lyophilized fibrin sealant (FS) and a preparation method thereof. The lyophilized FS consists of the following independent components in parts by weight: 12-15 parts of lyophilized fibrinogen powder and 3-5 parts of lyophilized thrombin powder. In the invention, effective fibrinogen and a thrombin stabilizer as well as a reasonable formula are adopted so as to obtain the lyophilized FS which can be treated by a heat-resisting method. The heated preparation can inactivate lipid-enveloped and non-lipid-enveloped viruses and can be rapidly re-dissolved at room temperature, which greatly facilitates clinical use and is of great significance to first-aid fibrin glue.
Description
Technical field
The present invention relates to medical technical field, is a kind of lyophilizing fibrin sealant that can tolerate the high-temperature inactivation virus treated.
Background technology
Fibrin sealant is made up of two components: lyophilizing Fibrinogen and thrombin.Fibrinogen is a factor I, it is one of main component of plasma protein, molecular weight is about 340,000, Fibrinogen can form fibrin under the effect of thrombin, and then form firm fibrinous thrombus with platelet, thereby be used from the first aid hemostasis with thrombin one clinically, wound is bonding.
Fibrinogen and thrombin be easy inactivation when liquid state.So clinical used preparation is lyophilized preparation, redissolves with water for injection during use.There is safety issue in the clinical practice of fibrin sealant.Existing fibrin lyophilized formulations is blood product, if inactivation of virus is not thorough, will cause the infection of virus.
The virus inactivating method that is used for blood products large-scale production at present mainly contains S/D method, xeothermic deactivation method etc.The S/D method can be destroyed the outer membrane structure of lipid-coated virus, thus can effectively deactivation epidemic encephalitis type B, lipid-coated virus such as PRV (Pseudorabies virus).Because condition is gentle during S/D method fire extinguishing virus, to structure and active several no destruction of thrombin, thereby has been widely used in the large-scale production of thrombin.Yet the S/D method can not the non-lipid-coated virus of deactivation, therefore, only the goods of handling with the S/D method still have propagate non-lipid-coated virus such as hepatitis A may.
Dry heat treatment is deactivation fat peplos and non-lipid-coated virus effectively, xeothermic deactivation is as the final step of production routines such as the purification of Fibrinogen and thrombin, packing, lyophilizing, vacuum seal, can avoid the recontaminate of blood products, and cost is low, small investment, be convenient to large-scale production, a kind of ideal virus inactivating method of therefore can yet be regarded as.
But, still there is very big problem in existing xeothermic inactivation technology when being applied to Fibrinogen and thrombin production, as after 100 ℃ of processing in 30 minutes, Fibrinogen tends to occur slight atrophy, jaundice, the freeze-dried products time of redissolving and prolongs greatly, floccule, granule appear after the redissolution, and the vigor that solidifies surpasses 60 seconds, the thrombin complete deactivation.If handled in 72 hours with 80 ℃ of heating, serious atrophy, jaundice appear in the fibrin principle, and goods even can not redissolve show seriously degeneration of Fibrinogen; The thrombin complete deactivation.Some stabilizing agent can reduce xeothermic Denaturation to Fibrinogen and thrombin, but effect is still undesirable, even the xeothermic back of the Fibrinogen particularly under high concentration goods redissolve down at 37 ℃, the time is often above 30 minutes, and activity descends greatly, and the activity of thrombin still can't ensure.Therefore existing Fibrinogen and the thrombin preparation inapplicable above-mentioned xeothermic inactivation of viruses of filling a prescription is handled.
Summary of the invention
The purpose of this invention is to provide a kind of fibrin sealant of lyophilizing safely and efficiently and preparation method thereof, to overcome the above-mentioned defective that prior art exists.
The fibrin sealant of lyophilizing safely and efficiently of the present invention, form by the component of following parts by weight independently:
12～15 parts in lyophilizing Fibrinogen powder
3～5 parts in lyophilized thrombin powder;
Described " independence " refers to, and does not mix before the use;
Described lyophilizing Fibrinogen powder comprises the component of following parts by weight:
10～14 parts of Fibrinogens
0.8～1.2 part of stabilizing agent A
Described Fibrinogen powder as human plasma, porcine blood plasma or sheep blood plasma etc., can adopt business-like product from the blood plasma of deactivation, and its relevant quality index can be referring to 2010 editions officinal records;
Described stabilizing agent A is selected from more than one in organic acid, aminoacid, polysaccharide or the inorganic salt;
Described lyophilized thrombin powder comprises the component of following parts by weight:
3～5 parts of thrombins
3～5 parts of stabilizing agent B
Described thrombin as human plasma, porcine blood plasma or sheep blood plasma etc., can adopt business-like product from the blood plasma of deactivation, and its relevant quality index can be referring to 2010 editions officinal records;
Described stabilizing agent B is selected from more than one in polyhydric alcohol, polysaccharide, polysaccharide or the monosaccharide;
The preparation method of the fibrin sealant of lyophilizing safely and efficiently of the present invention comprises the steps:
(1) preparation of lyophilizing Fibrinogen powder:
Fibrinogen and stabilizing agent A are added in the entry, and fibrinogenic weight content is 4～8%, mixed dissolution, and lyophilizing then again 100 ℃ of deactivations 30 minutes, can obtain lyophilizing Fibrinogen powder;
(2) preparation of lyophilized thrombin powder
Thrombin and stabilizing agent B are added in the entry, and the weight content of thrombin is 1～2%, mixed dissolution, and lyophilizing then 100 ℃ of deactivations 30 minutes, can obtain the lyophilized thrombin powder again;
The fibrin sealant of lyophilizing safely and efficiently of the present invention is used for the first aid hemostasis, wound is bonding clinically.Using method is as follows:
Described lyophilizing Fibrinogen powder is mixed with water, and preparation becomes solution A, and in the solution A, the weight percent content of described lyophilizing Fibrinogen powder is 5～9%;
Described lyophilized thrombin powder is mixed with water, and preparation becomes solution B, and in the solution B, the weight percent content of described lyophilized thrombin powder is 1.5～3%;
Then solution A and solution B are mixed, put on the patient who needs treatment.
The present invention is by adopting effective Fibrinogen and thrombin stabilizing agent and rational formula, thereby a kind of lyophilizing fibrin sealant of can heat-resisting method handling is provided.Said preparation not only can be guaranteed deactivation fat peplos and non-lipid-coated virus through heat treated, and preparation is at room temperature redissolved fast, greatly facilitates clinical use, and especially the Fibrin Glue that first aid is used is extremely important.
The specific embodiment
Embodiment 1
Prescription:
13 parts in lyophilizing Fibrinogen powder, 3 parts in lyophilized thrombin powder
Described lyophilizing Fibrinogen powder comprises the component of following parts by weight:
12 parts of Fibrinogens, 1 part of stabilizing agent A;
Described Fibrinogen powder is from the porcine blood plasma of deactivation;
Described stabilizing agent A is glycine, sodium citrate and sodium chloride;
Described lyophilized thrombin powder comprises the component of following parts by weight:
1.5 parts of thrombins, 1.5 parts of stabilizing agent B;
Described thrombin is from the porcine blood plasma of deactivation;
Described stabilizing agent B is glucose and glucosan;
Preparation method:
(1) preparation of lyophilizing Fibrinogen powder:
Fibrinogen and stabilizing agent A are added in the entry, and wherein, fibrinogenic weight content is 4%, mixed dissolution, and lyophilizing then again 100 ℃ of deactivations 30 minutes, can obtain lyophilizing Fibrinogen powder;
(2) preparation of lyophilized thrombin powder
Thrombin and stabilizing agent B are added in the entry, and wherein, the weight concentration of thrombin is 1%, mixed dissolution, and lyophilizing then 100 ℃ of deactivations 30 minutes, can obtain the lyophilized thrombin powder again.
(3) using method:
Described lyophilizing Fibrinogen powder is mixed with water, and preparation becomes solution A, and in the solution A, the weight percent content of described lyophilizing Fibrinogen powder is 5%;
Described lyophilized thrombin powder is mixed with water, and preparation becomes solution B, and in the solution B, the weight percent content of described lyophilized thrombin powder is 1.5%;
Then solution A and solution B are mixed, put on the patient who needs treatment.
Embodiment 2
Prescription:
15 parts in lyophilizing Fibrinogen powder, 5 parts in lyophilized thrombin powder
Described lyophilizing Fibrinogen powder comprises the component of following parts by weight:
13 parts of Fibrinogens, 2 parts of stabilizing agent A;
Described Fibrinogen powder is from the deactivation Ox blood plasma;
Described stabilizing agent A is arginine hydrochloride, sodium citrate and sodium chloride.
Described lyophilized thrombin powder comprises the component of following parts by weight:
2.5 parts of thrombins, 2.5 parts of stabilizing agent B;
Described thrombin is from the deactivation Ox blood plasma;
Described stabilizing agent B is glucosan and sucrose;
Preparation method:
(1) preparation of lyophilizing Fibrinogen powder:
Fibrinogen and stabilizing agent A are added in the entry, and wherein, fibrinogenic weight content is 5%, mixed dissolution, and lyophilizing then again 100 ℃ of deactivations 30 minutes, can obtain lyophilizing Fibrinogen powder;
(2) preparation of lyophilized thrombin powder
Thrombin and stabilizing agent B are added in the entry, and wherein, the weight concentration of thrombin is 1.5%, mixed dissolution, and lyophilizing then 100 ℃ of deactivations 30 minutes, can obtain the lyophilized thrombin powder again.
(3) using method:
Described lyophilizing Fibrinogen powder is mixed with water, and preparation becomes solution A, and in the solution A, the weight percent content of described lyophilizing Fibrinogen powder is 7%;
Described lyophilized thrombin powder is mixed with water, and preparation becomes solution B, and in the solution B, the weight percent content of described lyophilizing Fibrinogen powder is 2%;
Then solution A and solution B are mixed, put on the patient who needs treatment.
Claims (8)
1. a lyophilizing fibrin sealant safely and efficiently is characterized in that, is made up of the component of following parts by weight independently:
12～15 parts in lyophilizing Fibrinogen powder
3～5 parts in lyophilized thrombin powder.
2. lyophilizing fibrin sealant according to claim 1 is characterized in that, described lyophilizing Fibrinogen powder comprises the component of following parts by weight:
10～14 parts of Fibrinogens
0.8～1.2 part of stabilizing agent A.
3. lyophilizing fibrin sealant according to claim 2 is characterized in that, described Fibrinogen powder is from the serum of the animal of deactivation.
4. lyophilizing fibrin sealant according to claim 2 is characterized in that, described stabilizing agent A is selected from more than one in sodium citrate, glycine, arginine hydrochloride or the sodium chloride.
5. lyophilizing fibrin sealant according to claim 1 is characterized in that, described lyophilized thrombin powder comprises the component of following parts by weight:
3～5 parts of thrombins
3～5 parts of stabilizing agent B.
6. lyophilizing fibrin sealant according to claim 5 is characterized in that described thrombin is from the serum of the animal of deactivation.
7. lyophilizing fibrin sealant according to claim 5 is characterized in that, described stabilizing agent B is selected from more than one in glucosan, glucose, sucrose or the mannitol.
8. prepare the method for each described fibrin sealant of lyophilizing safely and efficiently of claim 1～7, comprise the steps:
(1) preparation of lyophilizing Fibrinogen powder:
Fibrinogen and stabilizing agent A are added in the entry, and fibrinogenic weight content is 4～8%, mixed dissolution, and lyophilizing then again 100 ℃ of deactivations 30 minutes, can obtain lyophilizing Fibrinogen powder;
(2) preparation of lyophilized thrombin powder
Thrombin and stabilizing agent B are added in the entry, and the weight content of thrombin is 1～2%, mixed dissolution, and lyophilizing then 100 ℃ of deactivations 30 minutes, can obtain the lyophilized thrombin powder again.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101829682A CN102258770A (en) | 2010-05-26 | 2010-05-26 | Safe and efficient lyophilized fibrin sealant (FS) and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN2010101829682A CN102258770A (en) | 2010-05-26 | 2010-05-26 | Safe and efficient lyophilized fibrin sealant (FS) and preparation method thereof |
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| CN102258770A true CN102258770A (en) | 2011-11-30 |
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105007841A (en) * | 2012-12-31 | 2015-10-28 | 乔治·D.·福卢什 | Lyophilized fibrin sealant for high volume hemorrhage |
| 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 |
| CN105617453A (en) * | 2016-01-08 | 2016-06-01 | 广州市众为生物技术有限公司 | Hemostasis biological product for surgical department and use method thereof |
| US20180099069A1 (en) * | 2016-10-11 | 2018-04-12 | St. Teresa Medical, Inc. | Hemostatic products |
| EP3242656A4 (en) * | 2015-01-06 | 2018-08-29 | St. Teresa Medical, Inc. | Hemostatic products |
| US10828387B2 (en) | 2015-11-12 | 2020-11-10 | St. Teresa Medical, Inc. | Method of sealing a durotomy |
| US10953128B2 (en) | 2017-11-02 | 2021-03-23 | St. Teresa Medical, Inc. | Fibrin sealant products |
| CN113546697A (en) * | 2020-04-23 | 2021-10-26 | 国家纳米科学中心 | Microfluidic device and preparation method and application thereof |
| CN113797325A (en) * | 2021-09-29 | 2021-12-17 | 复旦大学 | Method for preparing hemostatic material based on jet milling technology |
-
2010
- 2010-05-26 CN CN2010101829682A patent/CN102258770A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105007841A (en) * | 2012-12-31 | 2015-10-28 | 乔治·D.·福卢什 | Lyophilized fibrin sealant for high volume hemorrhage |
| EP3242656A4 (en) * | 2015-01-06 | 2018-08-29 | St. Teresa Medical, Inc. | Hemostatic products |
| 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 |
| US10828387B2 (en) | 2015-11-12 | 2020-11-10 | St. Teresa Medical, Inc. | Method of sealing a durotomy |
| CN105617453A (en) * | 2016-01-08 | 2016-06-01 | 广州市众为生物技术有限公司 | Hemostasis biological product for surgical department and use method thereof |
| US20180099069A1 (en) * | 2016-10-11 | 2018-04-12 | St. Teresa Medical, Inc. | Hemostatic products |
| US10953128B2 (en) | 2017-11-02 | 2021-03-23 | St. Teresa Medical, Inc. | Fibrin sealant products |
| CN113546697A (en) * | 2020-04-23 | 2021-10-26 | 国家纳米科学中心 | Microfluidic device and preparation method and application thereof |
| CN113797325A (en) * | 2021-09-29 | 2021-12-17 | 复旦大学 | Method for preparing hemostatic material based on jet milling technology |
| CN113797325B (en) * | 2021-09-29 | 2023-11-21 | 复旦大学 | Method for preparing hemostatic material based on jet milling technology |
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Application publication date: 20111130 |