Stable liquid compound fibrillarin blocking agent, and its preparation and use

A technology of composite fiber and fibrinogen, which is applied in the field of preparation of liquid composite fibrin sealant, can solve the problems of unsatisfactory, decreased coagulation protein rate, and unstable radiation intensity, so as to eliminate damage and pain, promote sealing repair, The effect of promoting wound healing

Active Publication Date: 2009-08-05
SHANGHAI LIKANGRUI BIOLOGICAL ENG +3
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the synthetic sealing product is an organic polymer material, there are problems of absorption and rejection, so it is not ideal
Since the identification of biological protein suture products as adhesives in 1972, fibrin sealants based on human blood have been widely used in 1982, and the US FDA is concerned that the large-scale production of human blood products will lead to infectious hepatitis and AIDS. Popular, therefore, commercialization has been prohibited for a long time in the past, until 1998, no product was approved by the US FDA, but the product price is extremely expensive
The traditional fibrin sealant has more or less shortcomings in the medical effect due to its imperfection in technology and dosage form, which is mainly manifested in the following aspects: 1) The traditional fibrin sealant is frozen The dry dosage form needs to be dissolved and prepared when used, which takes a long time to dissolve and the procedures are cumbersome; and the whole process of freeze-drying and re-dissolving prevents the concentration of the main component of fibrinogen in the product from being very high; 2) The traditional process adopts "cryoprecipitation process" for separation and purification, The content and purity of the main components fibrinogen, factor X III and fibronectin obtained are relatively low; 3) the traditional process adopts Co60 radiation irradiation to kill viruses and bacteria in the product
The disadvantages of this method are: ①The radiation intensity of Co60 is not constant, and the effect on the product is not uniform, which may easily cause incomplete killing of bacteria and viruses; ②Bacteria remain in the product after radiation exposure, which is a potential heat source
③After Co60 radiation irradiation, the purity of fibrinogen in the product will decrease, the coagulable protein rate will decrease by about 10%, and the dissolution time will be greatly prolonged; The film strength is low, it can only be used for hemostasis and sealing of general wounds, and it cannot be used for effective adhesion of tissues, and the clinical effect is not good

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Selection of function enhancement factor: In this embodiment, factor XIII is selected as the function enhancement factor;

[0034] Stabilizer I selects a mixture of seaweed polysaccharide and glycine, and stabilizer II selects seaweed polysaccharide;

[0035] (1) Preparation of Part I:

[0036] ① Add saturated ammonium salt to the anticoagulant and virus-killing refrigerated plasma to produce a precipitate, and centrifuge to obtain the crude product precipitate.

[0037] ② The crude precipitate was dissolved in a citrate buffer with a pH value of 6.5, and then desalted by ultrafiltration to obtain a desalted solution.

[0038] ③ Add low-temperature 30% ethanol to the desalting solution, and centrifuge again to obtain a precipitate.

[0039] ④ After the precipitate was dissolved with citrate buffer, the organic solvent was removed by ultrafiltration again.

[0040]5. add function strengthening factor, and concentrate, add stabilizer I and citrate buffer solution, carr...

Embodiment 2

[0049] Selection of function enhancing factor: In this embodiment, the mixture of collagen and elastin is selected as the function enhancing factor; both stabilizer I and stabilizer II select a mixture of seaweed polysaccharide, albumin and glycine;

[0050] (1) Preparation of Part I:

[0051] ① Add saturated ammonium salt to the anticoagulant and virus-killing refrigerated plasma to produce a precipitate, and centrifuge to obtain the crude product precipitate.

[0052] ② The crude precipitate was dissolved in a phosphate buffer solution with a pH value of 8.0, and then desalted by ultrafiltration to obtain a desalted solution.

[0053] ③ Add low-temperature 20% polyethylene glycol to the desalting solution, and centrifuge again to obtain a precipitate.

[0054] ④ After the precipitate was dissolved in phosphate buffer, the organic solvent was removed by ultrafiltration again.

[0055] 5. add function strengthening factor, and concentrate, add stabilizer I and phosphate buff...

Embodiment 3

[0064] Selection of function enhancing factor: in this embodiment, the selection factor soluble chitosan is a function enhancing factor; stabilizer I selects a mixture of seaweed polysaccharide and glycine, and stabilizer II selects seaweed polysaccharide, glycine and globulin;

[0065] (1) Preparation of Part I:

[0066] ① Add saturated ammonium salt to the anticoagulant and virus-killing refrigerated plasma to produce a precipitate, and centrifuge to obtain the crude product precipitate.

[0067] ② The crude precipitate was dissolved in a citrate buffer with a pH value of 7.0, and then desalted by ultrafiltration to obtain a desalted solution.

[0068] ③ Add low-temperature 30% ethanol to the desalting solution, and centrifuge again to obtain a precipitate.

[0069] ④ After the precipitate was dissolved with citrate buffer, the organic solvent was removed by ultrafiltration again.

[0070] 5. add function strengthening factor, and concentrate, add stabilizer I and citrate ...

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PUM

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Abstract

The present invention relates to a stable liquid compound fibre protein blocking agent composition, its preparation method and application. The described stable liquid compound fibre protein blocking agent is formed from portion I and portion II. Said two portions are independently stored, when they are used, both are mixed so as to obtain several functions of blocking, repairing, blocking leakage and promoting healing in clinical surgery field. Said invention mainly utilizes addition of function-intensifying factor, stabilizing agent I and citrate buffer solution or phosphate buffer solution to provide a stable liquid compound fibre protein blocking agent which can be used as bone repairing material and medicine slowly-releasing carrier.

Description

technical field [0001] The invention relates to a stable liquid compound fibrin sealant composition, which can be used as a carrier of bone repair materials or a slow-release carrier of medicines, and can be used for tissue defect sealing, repairing, hemostasis, leakage plugging, anti-adhesion and promotion of wound healing , The invention also relates to a preparation method of the stable liquid composite fibrin sealant, which belongs to the field of medical products and technologies. technical background [0002] Medical sealing products have been developed for more than 90 years, and they are mainly divided into synthetic and biological sealing products. Since the synthetic sealing product is an organic polymer material, there are problems of absorption and rejection, so it is not ideal. Since the identification of biological protein suture products as adhesives in 1972, fibrin sealants based on human blood have been widely used in 1982, and the US FDA is concerned that ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/42A61L27/50A61P19/08
Inventor 吴昌琳刘光万
Owner SHANGHAI LIKANGRUI BIOLOGICAL ENG
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