RU2447848C2 - Method of abdominal adhesions prevention - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to surgery, and concerns prevention of postoperative adhesions in serous cavities and hollow organ lumens. For this purpose, at the last postoperative stage an aqueous, biosoluble, inert, polymer gel of the viscosity 0.6-0.93 mm/s is implanted in the affected regions with the preliminary deposited complexing substance d-penicillamine in ratio 15 mg per 100 ml of gel.

EFFECT: method provides effective prevention ensured by the integrated effect of the ingredients taken in optimal proportions.

5 dwg, 1 ex

Description

The invention relates to medicine, in particular to surgery.

Closest to the claimed solution is the method of prevention described by Verbitsky D.A. (Verbitsky DA. The use of carboxymethyl cellulose gel for the prevention of adhesion formation in the abdominal cavity: dis. ... Ph.D. medical sciences. - SPb., 2004 - 134 p.), Which consists in the fact that with the aim of binding free calcium ions in the peritoneal fluid and blocking the cascade of fibrinogen polymerization reactions and the formation of fibrin, as the basis of adhesions, the complexing substance Trilon B is introduced into the abdominal cavity.

To achieve the optimal result from the use of Trilon B, it is necessary to know the concentration of calcium in the peritoneal fluid, if the amount of the drug is insufficient, then the effectiveness of its use will be reduced to zero. On the contrary, with an overdose, a significant decrease in the concentration of calcium in various tissues and organs will occur until hypoglycemia, which is complicated by ventricular arrhythmias, paresis and paralysis, respiratory failure, dynamic intestinal obstruction. In addition, Trilon B solution quickly eliminates from the implantation sites, since it is a liquid, therefore, a short residence time of substances in the pathological focus reduces the time of its therapeutic effect. Therefore, the main disadvantage of this method is the difficulty of dosing the drug and the fast rate of elimination from implantation sites. This technique does not allow to achieve the optimal concentration of calcium ions and, therefore, to control the process of adhesion formation.

EFFECT: development of a new effective method for the prevention of adhesions in serous cavities and lumens of hollow organs (uterus, fallopian tubes, esophagus) of a human and animal body.

The technical result is achieved by the fact that at the last stage of the operation, a bio-soluble, inert polymer gel with a viscosity of 0.6-0.93 mm / s with d-penicillamine pre-deposited in it in the ratio of 15 is implanted in the areas of damaged areas (serous cavities or lumen of the hollow organs) mg per 100 ml of gel.

A substance with the chemical name d-penicillamine is an active component of an immunomodulating drug under the trade name Kuprenil of the Kutnovsky Pharmaceutical Plant Polfa (Poland) (Analogs: Artamine, Beratsillin, Kuprimin, Kupripen, Depamine, Distaine, beta-Mercaptowalin, Mercaptil, Metalkal, Salka Trolled, etc.)

Pharmacological action: the main property of d-penicillamine is its high complexing activity against metal ions. It binds mainly ions of mercury, lead and iron, as well as calcium, which are known to play a significant role in the process of adhesion formation. In addition, d-penicillamine inhibits collagen synthesis in the body (participates in the formation of fibrinogen polymerization) and normalizes the ratio between its soluble and insoluble fractions, contributing to this inhibition of the development of the sclerosing process in tissues.

Total formula: C ₅ H ₁₁ NO ₂ S-HCI

Structural formula:

Molecular mass: 135.7 g.

International name: d-Penicillamine

Pharmacological group: antidote for metal poisoning.

The drug is well tolerated, does not have mutagenic, polyclonal activity, antigenic properties, does not have allergenic, mutagenic, embryotoxic, teratogenic carcinogenic effects (Dobritsa V.P. et al., 2001).

The pronounced immunomodulating properties of the d-penicillamine preparation, the absence of toxicity and other negative effects allow many researchers to express an opinion on the advantage of this drug over other drugs that correct immune processes in the treatment of various diseases.

D-penicillamine is currently widely used in clinical practice. Despite this, the available literature does not contain any information about the effect of the drug on the regeneration of damaged tissues and its effectiveness as a preventive anti-adhesive agent. Thus, the proposed method can simultaneously achieve a barrier effect and control the process of fibrinogenesis, as well as correct violations of the local immune response.

The invention is illustrated by the figures:

Figure 1 shows a planar adhesion between the cecum and the ventral wall.

Figure 2 shows the adhesion-free cecum and ventral wall.

Figure 3 shows a cross section of the cecum and the ventral wall on the 14th day of the experiment with simulated adhesions (ok. Mallory, 8 * 20 * 6), coarse connective tissue is visualized, the parietal and visceral peritoneum is thickened, fibrously changed, the area of connective tissue fusion is determined by the degeneration of the muscle layer of the intestine with the phenomena of disorganization of the course of muscle fibers.

Figure 4 shows a transverse section of the cecum on the 14th day of the experiment (ok. According to Mallory, at. 8 * 20 * 6), the peritoneum covering the defect does not differ from the intact, only in the deep layers are the focal fields of fibrosis, signs of inflammation in peritoneum is not determined.

Figure 5 presents the average values of the severity of adhesions in the comparison groups.

THE METHOD IS CARRIED OUT AS FOLLOWS.

At the last stage of the operation, those areas in which there is a high likelihood of adhesions (for example, organs of the serous cavities, lumen of the hollow organs: uterus, fallopian tubes, esophagus) are treated with a sterile bio-soluble inert polymer gel of the required viscosity (0.6-0.93 mm / c) to achieve a barrier effect with the complexing substance d-penicillamine deposited in them. The amount of active substance in the mixture is 15 mg per 100 ml of gel, because it is this amount of complexing drug that allows you to achieve the desired level of free calcium ions so that the cascade of adhesion reactions does not start. The obtained implant of a polymeric absorbable aqueous gel with the complexing substance d-penicillamine deposited in it is applied prophylactically to the visceral (parietal) serous cover using a syringe, tuffer, spatula or injected into the lumen of hollow organs with a syringe or catheter. Also, in addition to topical application of a bio-soluble inert polymer, a combination of the oral course administration of d-penicillamine with joint intra-abdominal gel implantation is possible.

EXAMPLE OF SPECIFIC PERFORMANCE

As a prophylactic, we used an aqueous bio-soluble inert polymer 3% methylcellulose gel with a viscosity of 0.9 mm / s with the substance of the complexing substance d-penicillamine deposited in it at the rate of 15 mg per 100 ml of gel. The method was tested on a model of adhesions of the abdominal cavity. Under aseptic conditions, two series of male Wistar rats (30 animals each) reproduced the adhesion process by scarification of the cecum before the appearance of “bloody dew” and hydraulic dissection of the parietal peritoneum (Lipatov VA, 2001). Moreover, the first series was a control and amounted to 3 groups of animals, and the second experimental one, included 5 groups depending on the form and method of administration of the drug.

After the adhesion process was simulated, 2 ml of the mixture were implanted in the animals of the experimental series in the places of deserted portions of the peritoneum; other experimental subjects underwent oral d-penicillamine per 2 ml of isotonic solution (0.9% NaCl) at a rate of 1.5-2 g per day. Animals were withdrawn from the experiment on day 14 by overdose of ether anesthesia. Rats underwent autopsy, a thorough study of the abdominal organs, assessing the severity of the adhesive process visually and using the technique of semantic differential (a scoring system consisting of assessing the prevalence of the adhesion process, deformation of the abdominal cavity and the severity of certain types of adhesions, taking into account the significance coefficient of each indicator). The parietal peritoneum and abdominal organs were subjected to histological examination according to the generally accepted method with fixation in neutral formalin, paraffin embedding, hematoxylin-eosin staining of the sections, according to Bath Guizot, impregnation with silver according to Foote and staining using the SIC reaction. The research results were processed statistically (calculated average values, student criterion, conjugation coefficient, Chi-square, linear regression and correlation methods were used).

We did not find statistically significant differences in the general condition, indicators of a clinical blood test, or leukocyte indices between the control and experimental groups. In the control series, adhesions occurred in all animals, the severity of the adhesion process by the method of semantic differential was 3.39 ± 0.18 points. In the experimental series, only four animals had soldering of the omentum to the median postoperative scar, and the severity of adhesions by the method of semantic differential was only 0.02 ± 0.001 points.

In a histological study in animals of the first series, the morphological organization of adhesions corresponded to the term for removing the animal from the experiment. The evolution of newly formed connective tissue tended to distant differentiation. The parietal and visceral peritoneum of animals of the 1st series is thickened, fibrotic changes. In the area of connective tissue fusion, dystrophy of the muscle layer of the intestine with the phenomena of disorganization of the course of muscle fibers is determined. Histological examination of the peritoneum of animals of the 2nd series: the peritoneum covering the defect does not differ from the intact, only in the deep layers focal fields of fibrosis are determined, signs of inflammation in the peritoneum are not determined.

Thus, the combined use of d-penicillam on a methyl cellulose gel significantly reliably reduces in the experiment the likelihood of a postoperative adhesive process of the abdominal cavity (P <0.05), which opens up prospects for its use in the clinic for the prevention of postoperative adhesion formation and complications associated with it.

Claims (1)

A method for the prevention of postoperative adhesions in serous cavities or in the lumen of hollow organs by using during surgery an agent including a bio-soluble, inert, polymer gel, characterized in that at the last stage of the operation, a gel of 0.6-0.93 viscosity is implanted into the sites of the damaged areas. mm / s with preliminary deposition in it of the complexing substance of d-penicillamine in the ratio of 15 mg per 100 ml of gel.

Images