A kind of absorbable composite material and preparation method for topical acute hemostasis based on oxidizing bacteria cellulose

文档序号:1747318 发布日期:2019-11-29 浏览:39次 中文

阅读说明:本技术 一种基于氧化细菌纤维素的用于局部急性止血的可吸收复合材料及其制备方法 (A kind of absorbable composite material and preparation method for topical acute hemostasis based on oxidizing bacteria cellulose ) 是由 洪枫 袁海彬 陈琳 于 2019-09-06 设计创作,主要内容包括:本发明涉及一种基于氧化细菌纤维素的用于局部急性止血的可吸收复合材料及其制备方法,通过以细菌纤维素为底物制备氧化细菌纤维素,再与多聚阳离子电解质进行复合;或者通过以细菌纤维素为底物制备氧化细菌纤维素,再与多聚阳离子电解质进行静电吸附自组装,并对凝血促愈因子进行包裹负载而得。本发明同时具备急性止血、广谱抗菌、促进愈合及体内吸收的特性;制备方法绿色环保,复合均匀高效,得到的复合材料安全性高,在高级功能敷料领域具有良好的市场应用前景。(The absorbable composite material and preparation method for topical acute hemostasis that the present invention relates to a kind of based on oxidizing bacteria cellulose, substrate prepares oxidizing bacteria cellulose by being using bacteria cellulose, then compound with the progress of polycation electrolyte;Or by preparing oxidizing bacteria cellulose using bacteria cellulose as substrate, then with polycation electrolyte carry out Electrostatic Absorption self assembly, and promotees to be cured the factor to blood coagulation and carry out package load and obtain.The present invention is provided simultaneously with acute hemostasis, broad-spectrum antiseptic, the characteristic for promoting healing and body absorption;Preparation method is environmentally protective, and compound uniform high-efficiency, obtained composite material is highly-safe, has good market application prospect in Premium Features dressing field.)

1. a kind of absorbable composite material for topical acute hemostasis based on oxidizing bacteria cellulose, it is characterised in that: logical It crosses and prepares oxidizing bacteria cellulose by substrate of bacteria cellulose, then is compound with the progress of polycation electrolyte;Or pass through Oxidizing bacteria cellulose is prepared by substrate of bacteria cellulose, then carries out Electrostatic Absorption self assembly with polycation electrolyte, And the more factor is promoted to blood coagulation and carries out package load and obtains.

2. absorbable composite material according to claim 1, it is characterised in that: the oxidizing bacteria cellulose passes through with thin Fungin is substrate, is obtained after alkali purifies and is rinsed with deionized water to neutrality.

3. absorbable composite material according to claim 1, it is characterised in that: the polycation electrolyte includes shell One or more of glycan, polylysine, quaternary ammonium salt;Blood coagulation promotees to be cured the factor to include one of fibrin ferment, collagen Or it is several.

4. a kind of preparation method of the absorbable composite material for topical acute hemostasis based on oxidizing bacteria cellulose, packet It includes:

(1) using bacteria cellulose as substrate, oxidizing bacteria cellulose suspension is prepared;

(2) polycation electrolyte solution is added dropwise in oxidizing bacteria cellulose suspension and carries out Electrostatic Absorption from group Reaction cartridge then takes out, and rinses, and freeze-drying obtains the absorbable composite material to stop blooding for topical acute;

Alternatively, blood coagulation is promoted to be cured factor aqueous solution and be added in oxidizing bacteria cellulose suspension to impregnate absorption, then poly is positive Ionic electrolytes solution is added dropwise to progress Electrostatic Absorption self-assembling reaction in oxidizing bacteria cellulose suspension, then takes Out, it rinses, freeze-drying obtains the absorbable composite material to stop blooding for topical acute.

5. the preparation method according to claim 4, it is characterised in that: the oxidizing bacteria cellulose in the step (1) is outstanding The preparation step of turbid is as follows: bacteria cellulose film being broken up, at room temperature through TEMPO/NaBr/NaClO mixed oxidization system It is obtained after oxidation, eccentric cleaning and dialysis.

6. the preparation method according to claim 4, it is characterised in that: the polycation electrolyte in the step (2) Solution is chitosan/dilute acid soln, the polylysine aqueous solution of 0.1-1% or the organosilicon quaternary ammonium salt of 1-10% of 1-5% Aqueous solution.

7. the preparation method according to claim 4, it is characterised in that: the blood coagulation in the step (2) promotees to be cured the factor to be dense Degree is 0.1-10mg/mL collagen aqueous solution or the fibrin ferment of 0.01-1mg/mL.

8. the preparation method according to claim 4 or 7, it is characterised in that: blood coagulation in the step (2) promote to be cured the factor with The mass ratio of oxidizing bacteria cellulose is 1:1-10:1.

9. the preparation method according to claim 4, it is characterised in that: the dipping adsorption time in the step (2) is 0.5-5 hours.

10. the preparation method according to claim 4, it is characterised in that: the Electrostatic Absorption self assembly in the step (2) is anti- It is 1-60 minutes between seasonable.

Technical field

The invention belongs to bio-medical composition technical field, in particular to a kind of use based on oxidizing bacteria cellulose In the absorbable composite material and preparation method of topical acute hemostasis.

Background technique

Absorbable hemostatic material is a kind of for wound bleeding position, can quick-acting haemostatic powder, and within a certain period of time can The bio-medical material being absorbed by the body.Its maximum feature is: sewing up a wound only applied to difficulty local in human body or animal body Blood, while realizing quick-acting haemostatic powder, can degradation in vivo, without take out, thus avoid hemostasis after the completion of remove dressing two Secondary injury.Currently used Absorbable hemostatic material has Fibrin Glue class hemostatic material, gelfoam class hemostatic material, oxidation Cellulose family hemostatic material and chitosan class hemostatic material etc..The each not phase of the hemostatic mechanism and application method of these hemostatic materials Together, haemostatic effect also has very big difference.

Oxidized regenerated cellulose (Oxidized Regenerated Cellulose, ORC) is prepared into for the first time in nineteen sixty Function is plant cellulose gauze-like or cotton shape Absorbable hemostatic material of the oxidation processes as cellulosic acid after regeneration, tool There are the appearance and quality of cotton yarn, it is soft and belittle, it is easy to wrap, applies, filling etc. operates.Its hemostatic mechanism is by surgical wound surface blood In platelet aggregation on mesh gauze, using hemostatic gauze as hemostatic substrate, meet blood after quickly form gel black object Matter, condensation clot is to achieve the purpose that hemostasis.It passes through physical action independent of clotting mechanism normal in human body Promote blood clotting rapidly, effectively controls thin vessels bleeding.Currently, only the U.S. and Britain can produce such product, clinically The absorabable hemostatic gauze Surgicel (speed i.e. yarn) used is exactly the product of Johnson Co..The speed i.e. main component of yarn is just It is oxidized regenerated cellulose.C6 primary hydroxyl high selectivity in cellulose is oxidized into carboxyl and obtained by oxidized regenerated cellulose A kind of derivative of the cellulose arrived has been applied to all trades and professions at present, and the product of market sale depends on import, The country only has several companies and has produced similar hemostatic gauze.Although oxidized regenerated cellulose has many excellent performances, There is also some drawbacks to be not applied for bleeding profusely if hemostasis efficiency is not high, and anti-microbial property is weak and histocompatbility is low Deng.

Currently, having used natural/synthesis high molecular material or inorganic in some disclosures or the patent of invention of authorization Material is modified oxidized regenerated cellulose to improve its antibacterial and anthemorrhagic performance.As collagen (CN105079886A), Alginates (CN104013991A) and carbon nanotube (CN105056284A) etc..Although the above compound hemostatic material is to oxidation regeneration Cellulosic can have certain promotion, but improvement is poor, can only promote its partial properties, and can be to the life of material Object absorbability can adversely affect.

Summary of the invention

Technical problem to be solved by the invention is to provide a kind of stopping for topical acute based on oxidizing bacteria cellulose The absorbable composite material and preparation method of blood, solve oxidized regenerated cellulose anti-microbial property is weak, histocompatbility is low, only The slow-footed problem of blood.

The absorbable composite material for topical acute hemostasis that the present invention provides a kind of based on oxidizing bacteria cellulose, By preparing oxidizing bacteria cellulose using bacteria cellulose as substrate, then carry out with polycation electrolyte compound;Or it is logical It crosses and prepares oxidizing bacteria cellulose by substrate of bacteria cellulose, then carry out Electrostatic Absorption from group with polycation electrolyte Dress, and the more factor is promoted to blood coagulation and carries out package load and obtains.

The oxidizing bacteria cellulose through alkali by purifying and being rinsed with deionized water into using bacteria cellulose as substrate It is obtained after property.

The polycation electrolyte includes one or more of chitosan, polylysine, quaternary ammonium salt;Blood coagulation promotees More the factor includes one or more of fibrin ferment, collagen.

The absorbable composite wood for topical acute hemostasis that the present invention also provides a kind of based on oxidizing bacteria cellulose The preparation method of material, comprising:

(1) using bacteria cellulose as substrate, oxidizing bacteria cellulose suspension is prepared;

(2) polycation electrolyte solution is added dropwise in oxidizing bacteria cellulose suspension and carries out Electrostatic Absorption Self-assembling reaction then takes out, and rinses, freeze-drying, obtains topical acute hemostasis absorbable material;

Alternatively, by blood coagulation promote be cured the factor be added in oxidizing bacteria cellulose suspension impregnate adsorb, then by poly sun from Sub- electrolyte solution is added dropwise to progress Electrostatic Absorption self-assembling reaction in oxidizing bacteria cellulose suspension, then takes out, Rinsing, freeze-drying obtain topical acute hemostasis absorbable material.

The preparation step of oxidizing bacteria cellulose suspension in the step (1) is as follows: bacteria cellulose film broken up, It aoxidizes through TEMPO/NaBr/NaClO mixed oxidization system, is obtained after eccentric cleaning and dialysis at room temperature.

Polycation electrolyte solution in the step (2) is chitosan/dilute acid soln of 1-5%, 0.1-1% The organosilicone quaternary ammonium saline solution of polylysine aqueous solution or 1-10%.

Blood coagulation in the step (2) promotees to be cured the factor to be 0.1-10mg/mL collagen aqueous solution or 0.01-1mg/mL Fibrin ferment.

Blood coagulation in the step (2) promotees to be cured the factor and the mass ratio of oxidizing bacteria cellulose to be 1:1-10:1.

Dipping adsorption time in the step (2) is 0.5-5 hours.

The Electrostatic Absorption self-assembling reaction time in the step (2) is 1-60 minutes.

The present invention prepares oxidizing bacteria cellulose (OBC) by substrate of Nano bacteria cellulose, using its high-purity and greatly Specific surface area characteristic accelerates coagulation process.Charge, progress electrostatic opposite using OBC and polycation electrolyte simultaneously Adsorb self-assembling reaction carry out it is compound, can also introduce wherein blood coagulation promote be cured the factor, be prepared while having acute hemostasis, Antibacterial and the absorbable composite material for promoting more function.

Beneficial effect

(1) material of the present invention prepares oxidizing bacteria cellulose by substrate of bacteria cellulose, and carboxyl-content is higher, nanometer Scale fiber, specific surface area is bigger, and the degree of polymerization is lower, and haemostatic effect is more preferable, and biodegradable properties are more preferable, it is easier to by human body It absorbs.

(2) the present invention charge carry out Electrostatic Absorption opposite with polycation electrolyte using oxidizing bacteria cellulose Self assembly preparation, without using additional crosslinking agent;Meanwhile the addition of polycation electrolyte improves material and promotees blood coagulation and resist Bacterium characteristic.

(3) present invention is by using the big specific surface area of oxidizing bacteria cellulose, sufficiently absorption blood coagulation promote to be cured the factor it Afterwards again with polycation electrolyte carry out Electrostatic Absorption self-assembling reaction, finally obtained material be provided simultaneously with acute hemostasis, Antibacterial, rush is cured and absorbable characteristic.

(4) raw material of the present invention is green environment protective biological material, can be according to reality without the chemical substance being harmful to the human body Situation and feature are prepared into various shape, and safety and environmental protection can degrade rapidly in the environment after discarding, can be used as a kind of functional And environmentally protective functional material.

(5) preparation method is simple by the present invention, and compound uniform high-efficiency does not use crosslinking agent, will not be to synthetic Original structure damages, environmentally protective, can industrialized production, have good market application prospect.

Detailed description of the invention

Fig. 1 is the flow diagram of preparation method of the present invention;

Fig. 2 is the product figure of embodiment 1-6 material prepared;Wherein, 1 is oxidizing bacteria cellulose (OBC), and 2 be oxidation Bacteria cellulose/chitosan (OBC/CS), 3 be oxidizing bacteria cellulose/collagen/chitosan (OBC/COL/CS), and 4 be oxygen Change bacteria cellulose/polylysine (OBC/PL), 5 be oxidizing bacteria cellulose/organosilicon quaternary ammonium salt (OBC/SQA), and 6 be oxidation Bacteria cellulose/fibrin ferment/polylysine (OBC/TB/PL);

Fig. 3 is the ex vivo whole blood setting time test result of embodiment 1-6 material prepared.

Specific embodiment

Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, those skilled in the art Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited Range.

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