JPH07101865A - Intraperitoneal adhesion inhibitor - Google Patents

Abstract

PURPOSE:To obtain intraperitoneal adhesion inhibitor which contains carrageenin as an active ingredient and can prevent intestines from adhering to each other or occluding to keep postoperative patients well. CONSTITUTION:The adhesion inhibitor includes carrageenin, as an active ingredient, which is obtained from Gigartina tenella, a red algae, by extraction with hot water. After celiotomy, the inhibitor is intraperitoneally poured to cover the operated site in an amount of 10 to 200ml. The carrageenin solution becomes gel at room temperature depending upon its concentration and the gel can be applied into the abdominal cavity in an amount of 5 to 100g. The intraperitoneal adhesion caused by tissue drying and bleeding on operation and by tissue damages accompanied surgery operation can be prevented.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an intraabdominal adhesion preventive agent containing carrageenan as an active ingredient.

[0002]

2. Description of the Related Art Although the adhesion of the intestinal tract, which occurs after laparotomy and particularly during gastrointestinal surgery, tends to decrease with the improvement of surgical techniques and equipment, it is the current situation that it cannot be completely prevented, which is annoying to the surgeon. It's a big problem. In the field of gynecology, postoperative adhesions may also be accompanied by infertility due to oviduct obstruction and sometimes intestinal obstruction. Intraperitoneal adhesions do not always cause disability, but they may cause adhesive ileus, resulting in reoperation and worsening the prognosis of postoperative patients (Maegoshi Masamitsu et al., Surgical Treatment, 68, 1005 (1993). )).

[0003] Adhesion is a result of a mechanism of tissue repair by an inflammatory reaction as one of biological defense reactions, and is triggered by damage to the intestinal serosa or peritoneum. After receiving various stimuli, shedding of damaged serosa, exudation of fibrinogen, and fibrin deposition by the same mechanism as blood coagulation, and finally formation of fibrinous fusion with nearby tissues by the involvement of fibroblasts etc. This is believed to be the case (Osamu Sugimoto, Obstetrics and Gynecology, 53, 185 (1986)). At present, a method for preventing such adhesion has not been established, and attempts have been made to use various drugs and special membranes. As a drug to prevent adhesion, one that has a wound surface covering action centered on polymeric substances,
For example, sodium alginate (JP-A-57-1679)
19), sodium chondroitin sulfate (Oelsne
r G. et al., J. Reprod. Med., 32, 812 (1987)) and sodium hyaluronate (Urman B. et al., Fertil. Ster.
il, 56, 563 (1991)) and other high molecular weight polysaccharides have been found to be effective. Others, such as fibrinolytic substances and steroids, have been tried and some have been clinically used. However, it is difficult to say that all of them are effective.

[0004]

An object of the present invention is to provide an excellent intraabdominal adhesion preventive agent.

[0005]

[Means for Solving the Problems] In view of the above situation, the inventors of the present invention have conducted extensive studies on high molecular weight polysaccharides, and as a result, have found that carrageenan has an anti-adhesion effect superior to that of previously reported substances, and completed the present invention. It was

That is, the present invention relates to an intraabdominal adhesion preventive agent containing carrageenan as an active ingredient.

In the present invention, carrageenan can be obtained by hot water extraction from seaweed of the genus Sugirino belonging to the red algae. It is a polymeric polysaccharide containing sulfuric acid containing D-galactose and anhydro-D-galactose as constituent sugars, and has a wide range of uses as a thickener, stabilizer and gelling agent for foods.
The present inventors have completed the present invention from a completely new finding that intraperitoneal adhesion is prevented by administering carrageenan intraperitoneally after laparotomy.

The carrageenan in the agent for preventing intra-abdominal adhesion of the present invention is usually prepared in a gel solution of 0.1 to 1.0 W / V%. As the solvent, it is desirable to use a physiological saline solution or an appropriate electrolyte solution, for example, the peritoneal lavage solution (Table 1) described in JP-A-2-304026.

[0009]

[Table 1]

The intraabdominal adhesion-preventing agent of the present invention is used after laparotomy.
It is preferably injected intraperitoneally and applied to cover the surgical site. The injection volume may be appropriately selected according to the age, body weight, sex difference, symptom and intra-abdominal injury area, and preferably in the range of 10 to 200 ml. Further, the carrageenan solution gels at room temperature depending on the concentration, and the gel can be applied intraperitoneally as it is. The application amount is preferably 5 g to 100 g of gel.

If desired, the agent for preventing intra-abdominal adhesion in the present invention can contain other medicinal components in addition to carrageenan.

[0012]

EXAMPLES The present invention will be described in detail below with reference to Examples and Test Examples conducted for the agent for preventing intra-abdominal adhesion of the present invention.

[Example 1] 10 g of carrageenan was added with the peritoneal lavage fluid shown in Table 1 and dissolved with stirring at room temperature for 3 to 4 hours. You may heat when melt | dissolving. After the solution became uniform, the total amount of the peritoneal lavage solution was adjusted to 1000 ml to obtain the intended 1.0% intraabdominal adhesion inhibitor. A physiological saline solution may be used instead of the peritoneal lavage solution.

The obtained anti-abdominal adhesion agent becomes a gel at room temperature.

[Examples 2 to 4] In the same manner as in Example 1,
A carrageenan concentration of 0.02% (Example 2), 0.1% (Example 3) and 0.5% (Example 4) were obtained as intraperitoneal adhesion preventive agents.

The obtained intraperitoneal adhesion preventive agent is in a solution state at room temperature at 0.02%, but becomes a gel at 0.1% and 0.5%.

[Comparative Solution 1] The peritoneal lavage fluid shown in Table 1 above was used as Comparative Solution 1.

[Comparative Solution 2] For comparison, sodium hyaluronate was used as a high molecular weight polysaccharide for which an adhesion preventing effect was reported. That is, in the same manner as in Example 1, 5 g of sodium hyaluronate was used in place of carrageenan to obtain the target comparative liquid 2.

[Test Example] The following adhesion model was prepared using male SD rats of 10 to 13 weeks of age. That is, under pentobarbital anesthesia, a laparotomy was performed about 3 cm from the xiphoid process to the lower part along the midline to the lower part for about 4 cm, and after removing epididymal fat on the left and right, 10 g from the ileocecal part to the oral side with dry gauze.
The ileum up to cm was rubbed 9 times (to the extent that bleeding was observed). Then, each intra-abdominal adhesion preventive agent (10 ml or 5 g in the case of a gel) of Examples 1 and 2 containing a predetermined concentration of carrageenan was applied intraperitoneally, and the abdomen was closed by double-layer suture. One week after the laparotomy, the state of intestinal adhesion was evaluated. The adhesion was evaluated by measuring the adhesion length (adhesion length) of the treated ileums and other intestinal tracts (jejunum, cecum, large intestine, etc.) to the treated ileum. In the same manner, the control group used the comparison solutions 1 and 10 ml, and the positive control group used the comparison solutions 2 and 10 m.
1 was injected intraperitoneally. The results are shown in Table 2.

[0020]

[Table 2]

From Table 2, carrageenan was 0.1 compared to the control group.
A good anti-adhesion effect was observed at ~ 1.0%, especially 0.5-
An excellent effect was recognized at 1.0%. This effect was superior to the known sodium hyaluronate.

Further, in the adhesion model used this time, similar evaluations were carried out with respect to known sodium alginate, sodium chondroitin sulfate and dextran 70. As a result, no adhesion prevention effect was observed.

From the above, it became clear that carrageenan has an excellent effect as an active ingredient of an intraabdominal adhesion preventive agent.

[0024]

INDUSTRIAL APPLICABILITY The agent for preventing intra-abdominal adhesion of the present invention can prevent intra-abdominal adhesion due to tissue dryness, bleeding, and tissue damage due to surgery during laparotomy. Therefore, postoperative intestinal adhesions and intestinal obstruction can be prevented and the prognosis of postoperative patients can be kept good.

Claims (1)

[Claims] 1. An intraperitoneal adhesion preventive agent containing carrageenan as an active ingredient.