CN1454667A - Convenient fibrin blocking agent - Google Patents
Convenient fibrin blocking agent Download PDFInfo
- Publication number
- CN1454667A CN1454667A CN 03111628 CN03111628A CN1454667A CN 1454667 A CN1454667 A CN 1454667A CN 03111628 CN03111628 CN 03111628 CN 03111628 A CN03111628 A CN 03111628A CN 1454667 A CN1454667 A CN 1454667A
- Authority
- CN
- China
- Prior art keywords
- fibrin
- fibrinogen
- buffer
- factor
- thrombin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 102000009123 Fibrin Human genes 0.000 title abstract 3
- 108010073385 Fibrin Proteins 0.000 title abstract 3
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 title abstract 3
- 229950003499 fibrin Drugs 0.000 title abstract 3
- 239000002981 blocking agent Substances 0.000 title 1
- 239000000872 buffer Substances 0.000 claims abstract description 11
- 108090000190 Thrombin Proteins 0.000 claims abstract description 9
- 229960004072 thrombin Drugs 0.000 claims abstract description 9
- 108010074864 Factor XI Proteins 0.000 claims description 30
- 108010049003 Fibrinogen Proteins 0.000 claims description 16
- 102000008946 Fibrinogen Human genes 0.000 claims description 16
- 229940012952 fibrinogen Drugs 0.000 claims description 16
- 102100030563 Coagulation factor XI Human genes 0.000 claims description 15
- 108010080379 Fibrin Tissue Adhesive Proteins 0.000 claims description 8
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims description 6
- 239000008363 phosphate buffer Substances 0.000 claims description 6
- 238000012856 packing Methods 0.000 claims description 4
- 239000002245 particle Substances 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 3
- 239000008176 lyophilized powder Substances 0.000 claims description 3
- 239000004531 microgranule Substances 0.000 claims description 3
- 230000023597 hemostasis Effects 0.000 abstract description 3
- 239000000853 adhesive Substances 0.000 abstract description 2
- 230000001070 adhesive effect Effects 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000007789 sealing Methods 0.000 abstract description 2
- 210000001835 viscera Anatomy 0.000 abstract description 2
- 108010071289 Factor XIII Proteins 0.000 abstract 2
- 229940012444 factor xiii Drugs 0.000 abstract 2
- 241001484259 Lacuna Species 0.000 abstract 1
- 208000035992 Postmortem Changes Diseases 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000000518 rheometry Methods 0.000 abstract 1
- 235000018102 proteins Nutrition 0.000 description 15
- 102000004169 proteins and genes Human genes 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- 239000012141 concentrate Substances 0.000 description 14
- 238000000034 method Methods 0.000 description 11
- 108010094028 Prothrombin Proteins 0.000 description 4
- 102100027378 Prothrombin Human genes 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 229940039716 prothrombin Drugs 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 238000000108 ultra-filtration Methods 0.000 description 4
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- JGSARLDLIJGVTE-UHFFFAOYSA-N 3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000004904 shortening Methods 0.000 description 2
- 238000012859 sterile filling Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000029663 wound healing Effects 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 208000031737 Tissue Adhesions Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 239000000535 fibrinogen concentrate Substances 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a convenient sealing agent for fibrin. It is made up of fibrin source 60-100 mg/ml, factor XIII (FXIII) 30-60 U/ml, thrombin 200-600 IU/ml and the buffer, the PH value is 6-8. the invention has rheology character, and strong adhesive ability, imitates the final period of physical cruor mechanism. It exerts functions of biological hemostasis, promotes the concrescence of wound, prevents organism conglutination, conglutinates viscera gap, seals lacuna organism in order to decrease the exudation, medicine releasing carrier slowly. It applies to all the modern surgical.
Description
(1), affiliated field
What the present invention relates to is a kind of medical preparation, specifically a kind of medical preparation that is used for surgical hemostasis, promotion wound healing etc.
(2), background technology
The healing of wound and hemorrhagely be not only the problem that modern surgery operation faces if handle untimelyly or improper simultaneously, also can bring life danger to the patient.Through years of researches, scientist has developed " human body glue ", and its Main Ingredients and Appearance is Fibrinogen and thrombin etc.Though its title is varied, needing only Main Ingredients and Appearance and action principle basic identical is exactly with a kind of product.Below with fibrin sealant (Fibrin sealant, FS) expression.This product simulation the human body self coagulation process final stage and work, simultaneously its composition is the protein of pure natural, so reduced the toxicity, side effect in the use to greatest extent.Can on a lot of magazines, newpapers and periodicals, medium, see or find about the advantage that the composition of this product and operation instruction, this product are compared with other similar products, also known simultaneously by the scientific and technical personnel in this area.But the use of FS is very loaded down with trivial details, and operation is trouble (seeing product and the operation instruction of FS) quite.So not only make troubles, and incur loss through delay rescue time sometimes to use.Particularly the redissolution of one of component of product fibrinogen concentrate is very difficult, and its dissolution time often is unfavorable for doctor's operation technique generally at 30-60 minute.
(3), summary of the invention
Do not need dissolving when the object of the present invention is to provide a kind of use or can dissolve fibrin sealant easy to use fast.
The object of the present invention is achieved like this: it is by Fibrinogen 60-100mg/ml, factor XI, plasma thromboplastin antecedent II (FXIII) 30-60U/ml, and the buffer of thrombin 200-600IU/ml and surplus is formed, and its pH value is at 6-8.Buffer wherein is phosphate buffer and Tris-Hcl buffer.Its dosage form can be at-20 ℃ cryogen after the solution packing; Also can be to be ground into the microgranule lyophilized powder of particle diameter between the 50-500 micron after the lyophilizing.
Product of the present invention has very strong rheological properties (as viscosity, elasticity), and very strong adhesive capacity arranged, imitate the final stage of human body clotting mechanism fully, the biological hemostasis of performance, promote wound healing, prevent the tissue adhesion, bonding internal organs breach, sealing defective tissue with minimizing ooze out, function such as slow releasing carrier of medication, be applicable in all modern surgery operations.Great advantage of the present invention is to dissolve rapidly, simplifies procedures, and increases work efficiency, thereby for shortening operative process, wins the quality time for rescuing the wounded simultaneously.If cryogen only need take out frozen product during use, be put under 37 ℃ of conditions and dissolve, the complete dissolution time of 2.5ml specification product was at 3-8 minute, and is simple to operation.If its solidifiable protein component dissolution time of microgranule lyophilized powder only needs 3-5 minute.Thereby, win the quality time for rescuing the wounded simultaneously for shortening operative process.
(4), specific embodiments
For example the present invention is done in more detail below and describes:
Embodiment one
The solidifiable protein concentrate mainly refers to Fibrinogen, factor XI, plasma thromboplastin antecedent II (FXIII) etc. among the present invention, can activate to solidify under corresponding thrombin catalysis in blood.Solidifiable protein concentrate in the invention can derive from human blood also can derive from any mammalian such as pig, cattle etc.The proteic separation of solidifiable can adopt any for the known method of those skilled in the art as freezing precipitation, ethanol precipitation, chromatography, any known sophisticated method that solidifiable albumen in the blood is separated purification of saltouing or the like.Press Fibrinogen 60-100mg/ml, factor XI, plasma thromboplastin antecedent II 30-60U/ml, the ratio of thrombin 200-600IU/ml is got raw material ready.Fibrinogen wherein and factor XI, plasma thromboplastin antecedent II are called the solidifiable protein concentrate again in a kind of component, concentration should reach 80-150mg/ml.Fibrinogen and factor XI, plasma thromboplastin antecedent II are mixed into the solidifiable protein concentrate, with solidifiable protein concentrate and prothrombin complex, respectively with phosphate buffer and the dissolving of Tris-Hcl buffer, adjust pH to 6-8, filtration sterilization then, ultrafiltration and concentration, sterile filling then.After all indexs detections are qualified, be put under-20 ℃ of conditions frozen.This product stock, traffic requirements are under-10 to-20 ℃ of conditions.
Embodiment two,
Press Fibrinogen 80mg/ml, factor XI, plasma thromboplastin antecedent II 50U/ml, the ratio of thrombin 400IU/ml is got raw material ready.Fibrinogen wherein and factor XI, plasma thromboplastin antecedent II are called the solidifiable protein concentrate again in a kind of component, concentration should reach 80-150mg/ml.Fibrinogen and factor XI, plasma thromboplastin antecedent II are mixed into the solidifiable protein concentrate, with solidifiable protein concentrate and prothrombin complex, respectively with phosphate buffer and the dissolving of Tris-Hcl buffer, adjust pH to 6-8, filtration sterilization then, ultrafiltration and concentration, sterile filling then.
Embodiment three,
Press Fibrinogen 60-100mg/ml, factor XI, plasma thromboplastin antecedent II 30-60U/ml, the ratio of thrombin 200-600IU/ml is got raw material ready.Fibrinogen wherein and factor XI, plasma thromboplastin antecedent II are called the solidifiable protein concentrate again in a kind of component, concentration should reach 80-150mg/ml.Fibrinogen and factor XI, plasma thromboplastin antecedent II are mixed into the solidifiable protein concentrate, with solidifiable protein concentrate and prothrombin complex, respectively with phosphate buffer and the dissolving of Tris-Hcl buffer, adjust pH to 6-8, filtration sterilization then, ultrafiltration and concentration, adopt and any can freeze dried methods be lyophilized into bulk, then the lyophilizing piece is blended into fine-powder shape granule with any method that can blend, and sieve and make the ground product particle diameter between the 50-500 micron, carry out the cillin bottle packing then.
Embodiment four
Press Fibrinogen 70mg/ml, factor XI, plasma thromboplastin antecedent II 50U/ml, the ratio of thrombin 300IU/ml is got raw material ready.Fibrinogen wherein and factor XI, plasma thromboplastin antecedent II are called the solidifiable protein concentrate again in a kind of component, concentration should reach 80-150mg/ml.Fibrinogen and factor XI, plasma thromboplastin antecedent II are mixed into the solidifiable protein concentrate, with solidifiable protein concentrate and prothrombin complex, respectively with phosphate buffer and the dissolving of Tris-Hcl buffer, adjust pH to 6-8, filtration sterilization then, ultrafiltration and concentration, adopt and any can freeze dried methods be lyophilized into bulk, then the lyophilizing piece is blended into fine-powder shape granule with any method that can blend, and sieve and make the ground product particle diameter between the 50-500 micron, carry out the cillin bottle packing then.
Claims (4)
1, a kind of fibrin sealant easy to use is characterized in that: it is by Fibrinogen 60-100mg/ml, factor XI, plasma thromboplastin antecedent II 30-60U/ml, and the buffer of thrombin 200-600IU/ml and surplus is formed, and its pH value is at 6-8.
2, fibrin sealant easy to use according to claim 1 is characterized in that: described buffer is phosphate buffer and Tris-Hcl buffer.
3, fibrin sealant easy to use according to claim 1 and 2 is characterized in that: its dosage form is at-20 ℃ cryogen after the solution packing.
4, fibrin sealant easy to use according to claim 1 and 2 is characterized in that: its dosage form is to be ground into the microgranule lyophilized powder of particle diameter between the 50-500 micron after the lyophilizing.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03111628 CN1454667A (en) | 2003-05-07 | 2003-05-07 | Convenient fibrin blocking agent |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03111628 CN1454667A (en) | 2003-05-07 | 2003-05-07 | Convenient fibrin blocking agent |
Publications (1)
Publication Number | Publication Date |
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CN1454667A true CN1454667A (en) | 2003-11-12 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN 03111628 Pending CN1454667A (en) | 2003-05-07 | 2003-05-07 | Convenient fibrin blocking agent |
Country Status (1)
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CN (1) | CN1454667A (en) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102448443A (en) * | 2009-05-28 | 2012-05-09 | 普罗菲布瑞克斯公司 | Dry powder fibrin sealant |
CN102448442A (en) * | 2009-05-28 | 2012-05-09 | 普罗菲布瑞克斯公司 | Treatment of tissue adhesions |
CN105007841A (en) * | 2012-12-31 | 2015-10-28 | 乔治·D.·福卢什 | Freeze-dried fibrin sealant for massive bleeding |
WO2017117996A1 (en) * | 2016-01-08 | 2017-07-13 | 广州市众为生物技术有限公司 | Biological product for surgical hemostasis and use method thereof |
US20220096708A1 (en) * | 2016-08-15 | 2022-03-31 | Guangzhou Bioseal Biotech Co. Ltd. | Hemostatic compositions and methods of making thereof |
-
2003
- 2003-05-07 CN CN 03111628 patent/CN1454667A/en active Pending
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102448443A (en) * | 2009-05-28 | 2012-05-09 | 普罗菲布瑞克斯公司 | Dry powder fibrin sealant |
CN102448442A (en) * | 2009-05-28 | 2012-05-09 | 普罗菲布瑞克斯公司 | Treatment of tissue adhesions |
US9089584B2 (en) | 2009-05-28 | 2015-07-28 | Profibrix B.V. | Treatment of tissue adhesion |
US9119897B2 (en) | 2009-05-28 | 2015-09-01 | Profibrix B.V. | Dry powder fibrin sealant |
CN105007841A (en) * | 2012-12-31 | 2015-10-28 | 乔治·D.·福卢什 | Freeze-dried fibrin sealant for massive bleeding |
WO2017117996A1 (en) * | 2016-01-08 | 2017-07-13 | 广州市众为生物技术有限公司 | Biological product for surgical hemostasis and use method thereof |
US20220096708A1 (en) * | 2016-08-15 | 2022-03-31 | Guangzhou Bioseal Biotech Co. Ltd. | Hemostatic compositions and methods of making thereof |
US11998656B2 (en) * | 2016-08-15 | 2024-06-04 | Guangzhou Bioseal Co., Ltd. | Hemostatic compositions and methods of making thereof |
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PB01 | Publication | ||
C12 | Rejection of a patent application after its publication | ||
RJ01 | Rejection of invention patent application after publication |