JP2853165B2 - Body tissue adhesion prevention film - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a novel body tissue adhesion preventing membrane containing cellulose produced by a microorganism.

The cellulose film produced by the microorganism of the present invention is used as a complex thereof to prevent adhesion of body tissues.

(Prior Art) Normally, mucous membranes and the like in a body can freely move without adhering to each other even when these mucous membranes and the like in the body are in contact with each other. For example, the intestinal tract and the abdominal wall in the peritoneal cavity are in contact but not adhered. However, when an inflammatory change is excited in such a site by some external factor (for example, performing a surgical operation in the body), an adhesion phenomenon may occur. This is because fibrin and the like are deposited on the tissue contact surface with the recovery of the inflammatory change. For this reason, for example, if the intestinal tract or the like adheres to another site, this may sometimes cause intestinal obstruction or the like later.

Various methods have been tried so far to prevent such adhesion. First, for the purpose of preventing peritoneal adhesion, a shielding film such as gutta percha, gelatin film,
In some cases, an anti-adhesion agent such as liquid paraffin, chondroitin sulfate, urea, nitramine, camphor oil, and olef oil has been used. Also, to prevent the deposition of fibrin involved in adhesion, diclomar, heparin,
Anticoagulants such as sulfated polysaccharides and dichromal, and proteolytic enzymes such as trypsin have also been used. In addition, it has been known to administer cortisone, ACTH, and the like, and to irradiate with X-rays.

However, none of the above methods or materials are sufficient to prevent adhesion, and no satisfactory method or material has been known until now.

(Problem to be Solved by the Invention) An object of the present invention is to provide a material that prevents adhesion between body tissues due to inflammatory changes in the body.

(Means for Solving the Problems) The object of the present invention can be solved by using a membrane-like cellulose in which fibrous cellulose having a width of 20 to 50 nm produced by a microorganism is entangled.

The membrane of the present invention may contain at least one of an adhesion inhibitor, a blood coagulation inhibitor, and a protease. That is, if a site where adhesion is likely to occur with cellulose is covered as a shielding film at the time of surgery, adhesion can be prevented. In addition, by impregnating the cellulose with an anti-adhesive agent, an anti-coagulant agent, a protease, etc., it is possible to prevent inflammation or inhibit the deposition of proteins that cause adhesion, thereby preventing adhesion more effectively. Is possible.

Cellulose produced by a microorganism used as a raw material of the present invention includes cellulose and those containing a heteropolysaccharide having cellulose as a main chain, and those containing glucans such as β and α. Hexoses, pentoses such as mannose, fructose, galactose, xylose, arabinose, rhamnose, uronic acid, and organic acids. These polysaccharides may be a single substance, or two or more polysaccharides may be mixed. Cellulose may be anything as long as it is as described above.

The microorganism that produces such cellulose is not particularly limited. For example, Acetobacter aceti subsp. Xylinum (Acetobacter aceti su
bsp.xylinum) ATCC10821 or the same Pastorian (A.
pasteurianus, A. ransens, Sarcina ventriculi, Bacterium xyloides, Pseudomonas bacteria, Agrobacterium bacteria, Rhizobium bacteria, and the like.

In order to produce and accumulate cellulose, a general method of culturing ordinary bacteria using the above microorganisms may be used. That is, it may be added to a normal nutrient medium containing a carbon source, a nitrogen source, inorganic salts, and, if necessary, organic trace nutrients such as amino acids and vitamins. The temperature may be controlled at 20 ° C. to 40 ° C. for culturing.

As a culture method, static culture is generally used. When the above-mentioned bacteria are inoculated into the above-described medium and cultured for one day to one month, a gel containing about 90% or more of liquid components is formed on the surface of the culture solution. Membranous cellulose is produced. The thickness of this film is between 0.01 and 20 mm. Cellulose produced in this way contains bacteria and medium components as well as liquid components.Thus, washing with dilute alkalis, dilute acids, organic solvents, hot water, surfactants, etc., alone or in combination, results in It is only necessary to remove harmful antigenic substances, pyrogenic substances, and the like when they are put in the container.

Such cellulose has a width according to electron microscopic observation.
It is known that ultrafine fibrous cellulose of 20 to 50 nm has a complex intertwined structure. Since the complex entanglement of the fibers contains a liquid component of about 10 to 200 times the weight of the fibers, the appearance is gel-like or leather-like.

Also, once the cellulose produced in this way is dried, the thin ribbon-like fibers constituting the gel-like cellulose adhere to each other by hydrogen bonding, resulting in a rigid film, but the hardness is adjusted. , A softening agent such as glycerin may be added to adjust the hardness. During drying, freeze-drying does not cause such hydrogen bonding,
When drying at the critical point, drying after solvent replacement, etc. are performed, a porous film can be obtained instead of a rigid film. It can be used after being impregnated with a liquid component such as physiological saline.

As described above, such a cellulose can contain a large amount of a liquid component between fibers.
By including at least one of an adhesion inhibitor, an anticoagulant, and a protease, adhesion can be prevented more effectively.

Examples of the anti-adhesion agent used include gutta percha, a shielding film such as a gelatin film, liquid paraffin, chondroitin sulfate, urea, nitromine, camphor oil, and olef oil. For example, trypsin, vanillin and the like are used as proteolytic enzymes. Further, other drugs, cortisone, ACTH and the like may be contained. Two or more of these drugs may be used together.

The method of inclusion may be such that the above-mentioned cellulose is immersed in the liquid component in which the above-mentioned drug is dissolved, or the gel-like cellulose is once pressed to squeeze out the internal liquid component, and then immersed. The liquid component in the gelled cellulose is usually a hydrophilic solvent in many cases, so if the component is soluble only in the lipophilic solvent, the liquid inside the gelled cellulose is once dissolved with an organic solvent or the like. By substituting or adding a surfactant, a drug can be contained.

As described above, since cellulose is in a gel state, there is also a secondary effect of drug delivery such that a contained drug gradually exudes to the outside. In order to positively utilize such an effect, it is possible to coat or contain another polymer material or the like in the gel-like cellulose. As the polymer material, two or more polymers of polyvinyl alcohol type, polyvinyl pyrrolidone type, polyacrylic acid type, starch type, cellulose derivative type, protein type such as gelatin, collagen and the like are used.

(Examples) Hereinafter, the present invention will be described with reference to examples.

Example 1. Sucrose 5 g / dl, yeast extract (Difco) 0.5 g / d
l, ammonium sulfate 0.5 g / dl, potassium phosphate 0.3 g / dl, magnesium sulfate heptahydrate 0.05 g / dl (pH 5.0)
After autoclaving at 20 ° C for 20 minutes, Acetobacter acetyl subsbysis xylinum (ATCC10821)
Was inoculated at a concentration of 1 × 10 ⁴ cells / ml. 400 ml of this solution was placed in a 20 cm square, 5 cm deep stainless steel container which had been autoclaved in advance, and cultured in air at 30 ° C. for 3 days. A gel-like film-like cellulose having a thickness of about 2 mm was formed on the surface of the culture solution. After collecting this,
Boiling was carried out for 1 hour in a 10-fold amount of a 2% sodium hydroxide solution. This boiling operation was repeated three times. By this operation, the cells and the medium components were removed. The boiling cellulose membrane was washed with excess water until the pH became neutral.

After the washed membrane-like cellulose was sandwiched between the intestinal tract and the abdominal wall in the abdominal cavity of the rat, the course after the operation was observed. 1
After examining whether adhesion had occurred after a month, adhesion was found where cellulose was not sandwiched, whereas adhesion did not occur where sandwiched. Also,
When a gelatin film was used as a control, dissolution of gelatin and adhesion of tissues were partially observed.

Example 2 The washed membrane cellulose prepared in Example 1 was immersed in a 1% heparin physiological saline solution for 10 days, and adhesion was observed in the abdominal cavity of the rat as in Example 1, and adhesion was prevented. Was done. Heparin gradually dissolved from the cellulose in the portion where the cellulose was not sandwiched, so that adhesion was suppressed.

(Effect of the Invention) Adhesion can be inhibited by using the body tissue adhesion preventing film of the present invention as a shielding film. Further, by impregnating a conventional anti-adhesion agent, adhesion can be more effectively prevented.

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Claims (2)

(57) [Claims] An anti-adhesion membrane for body tissue, comprising fibrous cellulose having a width of 20 to 50 nm produced by a microorganism. 2. The body tissue adhesion preventing film according to claim 1, further comprising at least one of an adhesion inhibitor, an anticoagulant, and a protease.