CN1820789A - A kind of biodegradable hemostatic sponge material and preparation method thereof - Google Patents

Abstract

The present invention discloses a kind of biodegradable hemostatic sponge material and its preparation process. The preparation process includes the following steps: 1. dissolving collagen like human collagen in distilled water to form 0.5-3 % concentration solution; 2. dissolving chitosan in dilute acid solution to form 0.5-2 % concentration solution and neutralizing with alkali; and 3. mixing the two kinds of obtained solution, vacuum defoaming and freeze drying to form sponge and Co-60 irradiating sterilization. The biodegradable hemostatic sponge material has high adhesion to tissue, less immune rejection, high toughness, excellent pain relieving and sterilizing effect, capability of promoting the recovery of damaged tissue, high hemostatic effect and greatly raised safety.

Description

A kind of biodegradable hemostatic sponge material and preparation method thereof

technical field

The invention relates to a biodegradable hemostatic sponge material and a preparation method thereof, belonging to the field of biomedical materials.

Background technique

Extensive bleeding and oozing during surgery and trauma are difficult problems that need to be addressed.

Collagen is the protein with the most content and widest distribution in animals. It is the main structural protein of the body and the main component of supporting tissue and connective tissue. It has good biocompatibility, hemostatic performance, and the function of promoting new cell formation and Cell Adhesion. Studies in recent years have shown that collagen can quickly stop bleeding within 10 seconds, promote granulation growth and wound healing, and prevent re-bleeding.

Human-like collagen is obtained by reverse-transcribing a section of mRNA of collagen known in the human body to generate cDNA, then repeating and modifying specific sequences, transforming it into Escherichia coli, and undergoing high-density fermentation, separation, extraction and purification. It is produced by Xi'an Juzi Invented and exclusively produced by Biogene Technology Co., Ltd. It fundamentally solves the problems of water insolubility and virus hidden dangers (mad cow disease, swine plague, bird flu) extracted from animals, and has good biological characteristics and functions, promoting new cell formation and promoting epithelial cells, fibroblasts The growth function is better than the collagen extracted from animals, and the immune rejection is low.

Chitin is a natural polymer material extracted from the shells of crustaceans such as shrimps and crabs and the cell walls of lower plants such as bacteria and algae. Chitosan is the deacetylation product of chitin and is the only alkaline substance in nature. polysaccharides. Studies in recent years have shown that chitosan has excellent properties such as pain relief, hemostasis, bacteriostasis, good biocompatibility and biodegradability, and is very suitable as a raw material for hemostatic materials.

The toughness of simple gelatin sponge or collagen protein hemostatic sponge is relatively poor, and there is no analgesic and antibacterial effect, as Chinese patent CN200410022462. Possibility of bleeding. At present, the collagen-chitosan composite hemostatic sponge combined with the two can effectively overcome the above shortcomings, such as patent application CN 02109638.4, but it has the disadvantages of hidden virus and slow recovery of wounds. International research on hemostatic sponges also mainly focuses on collagen and its modification, such as patents US 6649162, AU 726163B and RU 2122867, but they all use traditional animal collagen extraction, and there are inevitably viruses Hidden danger greatly limits the application of this hemostatic sponge.

Contents of the invention

One of the purposes of the present invention is to provide a biodegradable hemostatic sponge material combining human-like collagen and chitosan, to overcome the inevitable virus hidden dangers of gelatin and animal collagen sponges, and to improve the safety of the hemostatic sponge material. safety.

Another object of the present invention is to provide a method for preparing the above-mentioned biodegradable hemostatic sponge material, which has a simple process.

The biodegradable hemostatic sponge material of the present invention is made of human-like collagen and chitosan, the weight ratio of human-like collagen and chitosan can be (1～40): 1, and the optimal ratio is (3～ 40): 1, the human-like collagen used is a kind of human-derived collagen produced by high-density fermentation of recombinant Escherichia coli; the degree of deacetylation of the chitosan used is 50%-90%.

The preparation method of the biodegradable hemostatic sponge material is as follows: (1) dissolving humanoid collagen into a 0.5% to 3% solution with distilled water; (2) dissolving chitosan into a 0.5% to 2% solution with dilute acid solution, and use alkali to neutralize; (3) the above two solutions are mixed uniformly, vacuum degassed, and freeze-dried to form a sponge, which can be sterilized by cobalt ⁶⁰ irradiation.

In the above preparation method, the weight ratio of human-like collagen to chitosan is (1-40):1. The human-like collagen used is a kind of human-derived collagen produced by high-density fermentation of genetically recombined Escherichia coli; the degree of deacetylation of the chitosan used is 50% to 90%.

In the above-mentioned preparation method, the dilute acid used is any one of dilute hydrochloric acid, dilute acetic acid, dilute formic acid or allyl acrylic acid, and the concentration can be 0.2～0.8moL/L; The used alkali is dilute sodium hydroxide solution, dilute hydrogen Any one of potassium oxide solution or sodium bicarbonate solution, the concentration can be 0.05-0.5moL/L.

In the above preparation method, a plasticizer of 0.1% to 0.5% by weight is added to the mixed solution of humanoid collagen and chitosan, and the plasticizer is glycerol or 1.3-butanediol one or both.

In the above preparation method, 0.1%-0.5% of thrombin by weight is added to the mixed solution of humanoid collagen and chitosan.

Compared with the prior art, the biodegradable hemostatic sponge provided by the present invention has obvious technical advantages and advantages: the hemostatic sponge has good adhesion to tissues, low immune rejection, strong toughness, and good analgesic and antibacterial properties. It has a strong ability to promote the recovery of injured tissues, prevents the possibility of bleeding again, completely eliminates the inevitable virus hidden dangers of gelatin and animal collagen, and greatly improves the safety of use.

Detailed ways

The present invention will be further described below through specific implementation examples.

Example 1:

Dissolve human-like collagen into a 1.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 90% and a molecular weight of 10,000 Daltons into a 0.5% solution with 0.2moL/L acetic acid, and use 0.1moL /L of sodium bicarbonate solution for neutralization; then mix the two evenly at a volume ratio of 20:1, add 0.2% glycerol, and pack them in containers; after vacuum defoaming, freeze-dry to form a 2mm thick sponge ; After cobalt ⁶⁰ irradiation disinfection.

Example 2:

Dissolve human-like collagen into a 1.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 90% and a molecular weight of 10,000 Daltons into a 0.5% solution with 0.2moL/L acetic acid, and use 0.1moL /L of sodium bicarbonate solution for neutralization; then mix the two evenly at a volume ratio of 10:1, add 0.2% glycerol and 0.3% thrombin, and pack them in containers; freeze-dry after vacuum defoaming Form a 2mm thick sponge; Cobalt ⁶⁰ can be irradiated and sterilized.

Example 3:

Dissolve human-like collagen into a 2.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 90% and a molecular weight of 10,000 Daltons into a 1.0% solution with 0.2moL/L acetic acid, and use 0.1moL /L of sodium bicarbonate solution for neutralization; then mix the two evenly at a volume ratio of 15:1, add 0.2% glycerol, and pack in containers; after vacuum defoaming, freeze-dry to a thickness of 1.5mm Sponge; after cobalt ⁶⁰ irradiation disinfection.

Example 4:

Dissolve human-like collagen into a 2.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 90% and a molecular weight of 10,000 Daltons into a 1.0% solution with 0.2moL/L acetic acid, and use 0.1moL /L of sodium bicarbonate solution for neutralization; then mix the two evenly at a volume ratio of 8:1, add 0.2% glycerol and 0.2% thrombin, and pack them in containers; freeze-dry after vacuum defoaming Form a 1.5mm thick sponge; cobalt ⁶⁰ can be irradiated and sterilized.

Example 5:

Dissolve human-like collagen into a 1.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 75% and a molecular weight of 100,000 Daltons into a 0.5% solution with 0.3moL/L acetic acid, and use 0.2moL /L of sodium bicarbonate solution for neutralization; then mix the two evenly at a volume ratio of 10:1, add 0.4% 1.3-butanediol, and pack them in containers; freeze-dry to a thickness of 2mm after vacuum defoaming Sponge; after cobalt ⁶⁰ irradiation disinfection.

Embodiment 6:

Dissolve human-like collagen into a 1.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 75% and a molecular weight of 100,000 Daltons into a 0.5% solution with 0.3moL/L acetic acid, and use 0.2moL /L of sodium bicarbonate solution for neutralization; then mix the two evenly at a volume ratio of 6:1, add 0.4% of 1.3-butanediol and 0.3% of thrombin, and pack them in containers; after vacuum defoaming Freeze-dried into a 2mm thick sponge; cobalt ⁶⁰ irradiation disinfection can be done.

Embodiment 7:

Dissolve human-like collagen into a 2.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 75% and a molecular weight of 100,000 Daltons into a 1.0% solution with 0.3moL/L acetic acid, and use 0.2moL /L of sodium bicarbonate solution for neutralization; then mix the two evenly at a volume ratio of 6:1, add 0.4% 1.3-butanediol, and pack them in containers; freeze-dry to 1.5mm after vacuum defoaming Thick sponge; after cobalt ⁶⁰ irradiation disinfection.

Embodiment 8:

Dissolve human-like collagen into a 2.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 75% and a molecular weight of 100,000 Daltons into a 1.0% solution with 0.3moL/L acetic acid, and use 0.2moL /L of sodium bicarbonate solution for neutralization; then mix the two evenly at a volume ratio of 4:1, and add 0.2% glycerol, 0.2% 1.3-butanediol and 0.2% thrombin, and pack them in containers Medium; freeze-dried into a 1.5mm thick sponge after vacuum defoaming; sterilized by cobalt ⁶⁰ irradiation.

Embodiment 9:

Dissolve humanoid collagen into a 1.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 55% and a molecular weight of 400,000 Daltons into a 0.5% solution with 0.5moL/L hydrochloric acid, and use 0.1moL /L of sodium hydroxide sodium solution for neutralization; then mix the two evenly at a volume ratio of 5:1, and add 0.3% glycerol, and pack them in containers; after vacuum degassing, freeze-dry into 2mm thick Sponge; after cobalt ⁶⁰ irradiation disinfection.

Example 10:

Dissolve humanoid collagen into a 1.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 55% and a molecular weight of 400,000 Daltons into a 0.5% solution with 0.5moL/L hydrochloric acid, and use 0.1moL /L sodium hydroxide sodium solution for neutralization; then mix the two evenly at a volume ratio of 2:1, add 0.3% glycerol and 0.3% thrombin, and pack them in containers; freeze after vacuum defoaming Dried into a 2mm thick sponge; Cobalt ⁶⁰ irradiation disinfection can be done.

Example 11:

Dissolve human-like collagen into a 2.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 55% and a molecular weight of 400,000 Daltons into a 1.0% solution with 0.5moL/L hydrochloric acid, and use 0.1moL /L of sodium hydroxide sodium solution for neutralization; then mix the two evenly at a volume ratio of 3:1, add 0.3% glycerol, and pack in containers; freeze-dry to a thickness of 1.5mm after vacuum defoaming Sponge; after cobalt ⁶⁰ irradiation disinfection.

Example 12:

Dissolve human-like collagen into a 2.0% solution with distilled water; dissolve chitosan with a deacetylation degree of 55% and a molecular weight of 400,000 Daltons into a 1.0% solution with 0.5moL/L hydrochloric acid, and use 0.1moL /L sodium hydroxide sodium solution for neutralization; then mix the two evenly at a volume ratio of 1:1, add 0.3% glycerol and 0.3% thrombin, and pack them in containers; freeze after vacuum defoaming Dried into a 1.5mm thick sponge; cobalt ⁶⁰ can be irradiated and sterilized.

Claims (9)

1. A biodegradable hemostatic sponge material, characterized in that: the weight ratio of human-like collagen and chitosan is (1～40): 1. 2. The biodegradable hemostatic sponge material according to claim 1, characterized in that: human-like collagen is a human-derived collagen produced by high-density fermentation of genetically recombinant Escherichia coli. 3. The biodegradable hemostatic sponge material according to claim 1, characterized in that: the degree of deacetylation of chitosan used is 50%-90%. 4. the preparation method of biodegradable hemostatic sponge material according to claim 1, is characterized in that: (1) Dissolving the human-like collagen into a 0.5%-3% solution with distilled water; (2) dissolving chitosan into a solution of 0.5% to 2% with dilute acid, and neutralizing with alkali; (3) Mix the above two solutions evenly, vacuum defoam, freeze-dry to form a sponge, and irradiate and sterilize with cobalt ^-60 . 5. The preparation method of biodegradable hemostatic sponge material according to claim 4, characterized in that: the weight ratio of human-like collagen to chitosan is (1-40):1. 6. The preparation method of biodegradable hemostatic sponge material according to claim 4, characterized in that: the dilute acid used is any one of dilute hydrochloric acid, dilute acetic acid, dilute formic acid or dilute acrylic acid; It is any one of dilute sodium hydroxide solution, dilute potassium hydroxide solution or sodium bicarbonate solution. 7. according to the preparation method of the biodegradable hemostatic sponge material described in any one of claim 4, 5 or 6, it is characterized in that: in human-like collagen and chitosan mixed solution, also added 0.1% by weight % ~ 0.5% plasticizer. 8. The preparation method of biodegradable hemostatic sponge material according to claim 7, characterized in that: the plasticizer is one or both of glycerol or 1.3-butanediol. 9. according to the preparation method of the biodegradable hemostatic sponge material described in any one of claim 4, 5 or 6, it is characterized in that: in human-like collagen and chitosan mixed solution, also added 0.1% by weight %～0.5% thrombin.