JPH01301624A - Anti-adhesion material - Google Patents

Abstract

PURPOSE:To obtain a readily usable adhesion preventive material, consisting essentially of a specific water-soluble cellulosic derivative and capable of exhibiting preventing effects on occurrence of adhesion after surgical operation by simple operation with hardly any side effects. CONSTITUTION:An adhesion preventive material consisting essentially of a water-soluble cellulosic derivative expressed by the formula (R is H, alkyl, hydroxyalkyl, carboxyalkyl, etc.) (e.g. methyl cellulose, hydroxypropyl methyl cellulose or sodium carboxymethyl cellulose). The substitution degree is not especially limited if the compound expressed by the formula is soluble in water. The required water solubility thereof means that a homogeneous composition having free fluidity within the range of about 7 deg.C above and below physiological temperature as the center, i.e. 30-45 deg.C when the compound is mixed with physiological saline at a practical blending ratio.

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to a material for preventing adhesion of living tissues, and more particularly to a material for preventing the occurrence of adhesions after surgical operations.

(Prior Art) Adhesions after surgery have been of interest for a long time, but there is still no satisfactory prevention method.

Particularly after laparotomy, adhesions between intra-abdominal organs or between organs and the abdominal wall often occur, causing ileus (intestinal obstruction) in the small intestine or large intestine, internal organ damage, etc., and are a major problem.

Hitherto, fibrinolytic substances, membranous substances, oil agents, and the like have been tested to prevent adhesions, but an easy-to-use and reliable means has not yet been found. Recent examples include oxidized regenerated cellulose fabric (Japanese Patent Application Laid-open No. 62-47364) and hyaluronate gel film (Japanese Patent Application Laid-open No. 61-502729).
) have been proposed, but these methods attempt to physically cover the wound surface and are not suitable for preventing widespread adhesions such as intestinal adhesions within the abdominal cavity. Appropriate.

Further, Japanese Patent Application Laid-Open No. 57-167919 discloses a method using an aqueous sodium alginate solution. This technique does not have the above-mentioned drawbacks associated with the use of membrane-like materials, but it requires (1) a very highly concentrated solution; (2) it is an extract from seaweed and is composed of D-mannuronic acid and L. -The composition and arrangement of brocuronic acid differs depending on the raw material, and it is difficult to obtain a constant one. ■Alginate sulfur and lithium have the property of binding with divalent or higher valent metal ions such as calcium ions, making them insoluble and precipitating. However, there are drawbacks such as the risk of disrupting the balance of metal ions in the body by introducing a large amount of thorium alginate into the body.

(Problem to be solved by the invention) - In view of the existence of problems in the prior art as described below,
The present invention aims to provide an adhesion-preventing effect that can reliably prevent the occurrence of adhesions over a wide range with simple operations and does not adversely affect biological functions.

(Another Means to Solve the Problems) As a result of intensive research to achieve the object of the present invention, the present inventors have found that a simple solution can be achieved by using a composition containing a water-soluble cellulose derivative as a main component. It was discovered that adhesions can be effectively prevented by manipulation, and the present invention was completed based on this knowledge.

That is, the present invention provides a formula -i (wherein R is a hydrogen atom, an alkyl group, a hydroxyalkyl group, or a carboxyalkyl group).

It represents a plurality of atoms or groups selected from the group consisting of substituted alkyl groups such as sulfonated alkyl groups and aminoalkyl groups, and each R represents one of the plurality of atoms or groups, and R in the formula All of the above include all such plural types of atoms or groups. ) is an anti-adhesion material whose main component is a water-soluble cellulose derivative.

The cellulose derivative used in the present invention is a water-soluble cellulose derivative represented by the above general formula, and specific examples thereof include methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, and the like. Typical of these are easily available as commercial products, but they can be produced by reacting a cellulose raw material such as pulp with a (substituted) alkyl halide, or by further subjecting the product to a normal chemical reaction. It can also be obtained by doing.

There is no particular restriction on the degree of substitution of these cellulose derivatives as long as they are water-soluble. In the present invention, the water solubility required for the cellulose derivative means that when the cellulose derivative is mixed with water or physiological saline at a practical mixing ratio, the water solubility is within about 7 degrees above and below the physiological temperature, that is, 30 to 30 degrees. It refers to providing a uniform composition with free-flowing properties within a temperature range of 45°C.

Examples of such water-soluble cellulose derivatives include methylcellulose in which 27-32% of the hydroxyl groups in cellulose are substituted with methoxy groups, and 19-30% of the hydroxyl groups in cellulose are substituted with methoxy groups, and 4-12% are hydroxyl groups. Hydroxypropyl methylcellulose substituted with propoxy groups, 16-24% of hydroxyl groups in cellulose
Examples include sodium carboxymethylcellulose in which the carboxymethyl group is substituted with a thorium salt.

There is no particular limit to the molecular weight of each cellulose derivative, but from the viewpoint of anti-adhesion effects and ease of handling when used as an anti-adhesion material, the viscosity of a 1% aqueous solution at 20°C is 3.
Preferably, it is within the range of O-2000 cps.

The anti-adhesion material of the present invention is usually used as an aqueous solution of the above-mentioned cellulose derivative, and its concentration is preferably within the range of 0.1 to 5%, more preferably 0.5 to 3%.
．． It is 0%. In addition, in preparing this aqueous solution,
Water alone can be used as a solvent, but substances such as salts used in physiological saline and Ringer's solution can be added, and solutions such as physiological saline and Ringer's solution can also be used as they are. . However, the anti-adhesion material of the present invention is not limited to the above-mentioned aqueous solution, but may include, for example, a cellulose derivative encapsulated in microcapsules and suspended in water or physiological saline, or It may be in the form of a paste or cream. When the dosage form is other than such an aqueous solution, water, physiological saline, Ringer's solution, etc. may be used in combination at the time of application, so that the final aqueous solution within the above concentration range is obtained in the body cavity.

Furthermore, the anti-adhesion material of the present invention can be sterilized by a conventional method.

When the anti-adhesion material of the present invention is used to prevent abdominal adhesions, it is injected into the abdominal region after laparotomy so that the water distribution solution is uniformly distributed throughout the area.

The amount to be applied may be determined depending on the abdominal incision site and its area, and is not limited as long as it is applied to all abdominal incision sites. For normal open surgery, preferably 20,500 mff,
More preferably, the range is 50-350-3O0.

〔Example〕

Hereinafter, the present invention will be specifically explained with reference to Examples.

1 liter (1 liter) and methylcellulose (manufactured by Shin-Etsu Chemical Co., Ltd., Metrose 5M)
-4,00) was dissolved in distilled water to prepare a 1% aqueous solution.

A 2% aqueous solution was prepared by dissolving 1D-methylcellulose (Metrose 5lvl-1500, manufactured by Shin-Etsu Chemical Co., Ltd.) in distilled water.

Tosimethyl cellulose sodium (manufactured by Nippon Gosei Kagaku Kogyo 01, HH) was dissolved in distilled water to prepare a 1% aqueous solution.

Sample () Sodium Carboxymethyl Cellulose Synthetic Chemical Industry (
Co., Ltd., 4. Dissolve H) in distilled water to make 1% water? Yong? Prepared the night.

Extracting pillar-L” Sodium alginate (manufactured by Kimitsu Chemical Industry +T, ■-3
F) was dissolved in distilled water to prepare a 1% aqueous solution.

Evaluation test A 6-week-old Wistar Lasso l- (male) was treated as follows to generate adhesions in the cecal region, and the effect of the anti-adhesion material applied at that time was investigated. That is, (]) After the patient is put to sleep with air, Keklar is injected intramuscularly to anesthetize the patient.

(2) Shave the abdomen using electric clippers.

(3) Disinfect the abdomen using Hibitene.

(4) Open the abdomen and pull out the cecum.

(5) Rub the cecum with gauze and peel off the purple membrane around half the circumference of the cecum.

(6) Inject 1 mR of each sample of anti-adhesion material into the abdominal cavity.

(7) The inside of the incision was sutured with silk thread, and the skin was then closed with staple No. 1. Close with 0.

(8) After 4 weeks of rearing, the abdomen is opened again and the presence or absence of adhesions is examined.

The results of the evaluation in this way are shown in Table 1 as the number of adhesions based on the numerical value of (number of rats with adhesions/number of rats evaluated).

Incidentally, no side effects were observed at all due to the application of the anti-adhesion material of the present invention.

Table 1 Test interval Anti-adhesion material Number of adhesion 1" Not used 6/7 2 samples] 1/4 3 Sample 2 1/6 4 Sample 3 1/6 5 Sample 4 1/6 6"" Sample 5 4/7 *・Comparative Example [Effect of the Invention] The anti-adhesion material of the present invention uses an industrially quality-controlled cellulose derivative, and not only exhibits an excellent adhesion-preventing effect, but is also easy to use and has no side effects. It is something with few.

Patent applicant: Niki Zeon Co., Ltd.

Claims (1)

[Claims] General formula: ▲Mathematical formula, chemical formula, table, etc.▼ (In the formula, R is a hydrogen atom, an alkyl group, a hydroxyalkyl group, a carboxyalkyl group, a sulfonated alkyl group, an aminoalkyl group, etc. It represents multiple types of atoms or groups selected from the group consisting of substituted alkyl groups, each R represents one of the multiple types of atoms or groups, and all R's in the formula represent such multiple types of atoms or groups. An anti-adhesive material whose main component is a water-soluble cellulose derivative.