Medical multi-layer composite anti-adhesion membrane and preparation method thereof

Biocompatibility is an essential aspect of the medical device industry. Biocompatibility testing ensures that devices do not contain materials or substances that could be harmful to patients during initial use or over the course of time. Biocompatibility tests can be used to detect many possible negative side effects of a product on patient. These may include effects on cells and physiological systems, tissue irritation and inflammation, immunological and allergic reactions and the possibility of cellular mutations leading to cancer. Email:marketing@medicilon.com.cn web:www.medicilon.com

the following with reference to specific embodiments of the present invention will be further described below. It should be emphasized that the following description is merely exemplary and not intended to limit the scope and application of the present invention.

Step 1: 15 parts of polyvinyl alcohol associated cluster 1799 and 1 part of methyl cellulose steel (20g / L aqueous solution having a viscosity of 800 ~ 1200CP, degree of substitution 0.7) were dissolved in 84 parts of deionized water (mass , the same below), to obtain a mixed solution A. A mixed solution after casting, placed in -20 ° C freezer environment 12h, and then thawed at room temperature of above freezing - thawing total of S times to obtain a thickness of the gel film 500WI1.

Step 2: The eight parts of polyvinyl alcohol 1788,4 parts associated cluster methylcellulose steel (20g / L aqueous solution having a viscosity of between 800 and 1200 Qiu, degree of substitution 0.7), 4 parts of Tuen hydrated sulfate dissolved in front 84 parts of deionized water to obtain a mixed solution B. The mixed solution was cast Step B side of a surface of the resulting gel film, and evaporation of the solvent at room temperature to obtain a gel film comprising a thickness of the surface layer composite membrane IOOMi soluble film.

Step 3: Step 2 layer composite membrane obtained was treated with gamma sterilization cytotoxicity test, test and subcutaneous implantation of anti-blocking animal testing.

Cytotoxicity test: Test using L929 fibroblasts, according to the biological evaluation of the national standard GB / T16886.5 medical devices - Part 5, indirect contact method cytotoxicity tests prescribed in (MTT method). Different ratios (100%, 50%, 25%, 10%) relative growth rate mean cell layer composite membrane extract was respectively 88.7%, 91.5%, 95.2% and 96.8%, class 1 cytotoxic, indicating that the cytotoxicity layer composite film reaches the award criteria cytotoxic biomaterials as defined requirements.

biocompatibility tests: the test group selected nine New Zealand white rabbits (male and female, weighing 2.0-3.0kg), the double-layer composite film into the subcutaneous tissue in the back, were killed at 2,4,12 weeks (3 / times) to observe the local reaction, the material is removed and the surrounding tissue, 10% to 2 a wake fixed, paraffin-embedded sections, do fat staining, further observation layer composite membrane surrounding tissue inflammation, double evaluation histocompatibility complex film. The control group used nine New Zealand white rabbits (male and female, weighing 2.0-3.0kg), surgical sutures directly sutured wound back, respectively 2,4,12 weeks later (3 / times) and observe local reactions. Experimental group and control group rabbits survived, wound healing reached healed well into double-layer composite films were not part of the organization of the veins, edema, congestion, necrosis, indicating blend membrane materials are non-toxic and harmless to rabbits . In the immune response, the layer composite membrane surrounding tissue inflammatory cells decreased, fiber cyst gradually thinning. 2 weeks, 4 weeks after the rabbits in the experimental group than the control group, mild inflammatory response after 12 weeks in the experimental group subcutaneous site inflammation completely disappeared, formed around a very thin fibrous cysts, indicating histocompatibility of the film is good.

anti-blocking test animals: 16 rabbits were randomly divided into experimental and control groups, respectively, to accept median sternotomy incision Tuen, bags, gauze wipe repeatedly village, including two dirty wall, causing the village, including adhesions model. Experimental group was implanted with polyvinyl alcohol association - cluster methylcellulose steel double-layer composite membrane after implantation layer composite film of water-soluble film portion dissolved to form a sticky surface, without suture to make composite membrane bilayer and tissue adhesion. The control group did not implant material. Layer by layer to close the chest. One month after the animals were sacrificed, open the chest naked eye Tuen, including the extent and scope of the parietal and visceral adhesions. According to the literature class 4 Classification and grading standards to determine the adhesion score. 0: no adhesion; grade 1: mild, adhesions thin, pure separation easy bleeding; Level 2: moderate adhesion more closely, requires some sharp separation, a process operation in the amount of bleeding; grade 3: severe , close adhesion, require a lot of sharp separation, easy bleeding. Anti-adhesion film was visually observed in the experimental group used partially absorbed within a month, two rabbit village, blocking packet classification in Table Io

Step 1: 15 parts of polyvinyl alcohol 1799,1 parts associated cluster methylcellulose steel (20g / L aqueous solution viscosity 800-1200CP, degree of substitution 0.7), 1 part of the acid is dissolved in 83 trails parts of deionized water to obtain a mixed solution A. A mixed solution after casting, placed in -20 ° C freezer environment 12h, and then thawed at room temperature of above freezing - thawing total of S times to obtain a thickness of the gel film 500WI1.

Step 2: 8 parts of polyvinyl alcohol associated clusters 1788 and 4 parts of methylcellulose steel (20g / L aqueous solution having a viscosity of 800-1200CP, degree of substitution 0.7) were dissolved in 88 parts of deionized water to obtain a mixed solution B. The mixed solution was cast Step B side of a surface of the resulting gel film, and evaporation of the solvent at room temperature to obtain a gel film comprising a thickness of the surface layer composite membrane IOOwii soluble film.

Step 3: Step 2 layer composite membrane obtained was treated with gamma sterilization cytotoxicity test, test and subcutaneous implantation of anti-blocking animal testing.

Cytotoxicity Test: The same procedures as in Example 1 of the cytotoxicity assay. Different ratios (100%, 50%, 25%, 10%) relative growth rate mean cell layer composite membrane extract was respectively 92.6%, 94.5%, 95.9% and 98.2%, class 1 cytotoxic, indicating that poly ethyl alcohol association - cluster methyl cellulose composite membrane bilayer cytotoxicity reached the award criteria cytotoxic biomaterials as defined requirements.

Biocompatibility Test: Using the method of Example 1 was observed around the same layer composite membrane tissue inflammation, evaluate histocompatibility complex film. Experimental group and control group rabbits survived, wound healing reached healed well, no organization into a composite film parts of the veins, edema, congestion, necrosis, indicating blend membrane materials are non-toxic and harmless to rabbits. In the immune response, the composite membrane surrounding tissue gradually reduced inflammatory cells, fibrous encapsulation gradually thinning. 2 weeks, 4 weeks after the rabbits in the experimental group than the control group, mild inflammatory response after 12 weeks in the experimental group subcutaneous site inflammation completely disappeared, formed around a very thin fibrous cysts, indicating histocompatibility of the film is good.