Influence of Biopolymers from Marine Hydrobionts on the Course of the Wound Process in Colorectal Surgery (Clinical and Experimental Study)

The dissertation investigates the influence of biopolymers derived from marine hydrobionts — chitosan and tinrostim — on the wound process in colorectal surgery. The research is clinical and experimental in nature, comprising an experimental component using rat models and a clinical component involving proctological patients.

The study employs planimetry, histomorphology, cytological analysis of smear imprints, assessment of neutrophil phagocytic activity, and statistical methods. The results demonstrate that a chitosan-based gel with 0.1% tinrostim provides more effective healing of postoperative perineal wounds compared to traditional therapy with levomecetin/methyluracil ointment, reducing the frequency of infectious and inflammatory complications and the duration of hospitalization. A priority certificate has been obtained for the method, and a patent application has been filed.

Relevance of the research

Treatment of purulent-inflammatory processes of soft tissues is one of the most important problems in coloproctology.

In the structure of surgical pathology, purulent-inflammatory complications account for approximately 35%. Infectious complications are the cause of postoperative mortality in half of the patients who died in the surgical clinic [27, 43].

For many years, the problem of pathogenesis and treatment of purulent-inflammatory diseases of soft tissues has been at the center of close attention of clinicians [5, 34, 118, 155, 161, 172]. Surgeons of all specialties are confronted with purulent complications and must manage them. Despite the continuous improvement of general medical and surgical tactics, the significant economic costs of preventing such complications, they occupy one of the leading positions among the causes of patient mortality. Thus, the treatment of purulent-inflammatory processes of soft tissues remains a complex and urgent task, and it is unlikely that any other branch of surgery has such a number of controversial and unresolved questions.

In recent years, there has been growing interest in the development of wound-healing agents. This is due to the progressive increase in the number of injuries and surgical interventions, the severity of their course, and the rise in antibiotic-resistant and antibiotic-tolerant strains of microorganisms [72, 91, 172, 179].

In modern surgical practice, the main tasks in the treatment of infected wounds are sanitation and elimination of the focus of infection and intoxication, as well as activation of the body's defense forces and enhancement of its regenerative capabilities [199].

Operative wounds complicated by the development of pathogenic microflora, as well as purulent wounds with a high degree of microbial contamination, often lead to the formation of secondary or acquired immunodeficiency, the main manifestation of which is infectious postoperative complications [55, 89, 121]. In this regard, the use of immunocorrection methods in the regulation of the wound process acquires particular relevance [12, 17, 122].

Despite the fact that over the past 2–3 decades, a sufficient number of drugs possessing varying degrees of immunotropic activity have been created, there remains a deficit of highly effective, safe, and inexpensive immunocorrecting agents.

At present, biopolymers derived from hydrobionts (tinrostim, chitosan) are attracting increasing attention in surgical practice. A chitosan gel derived from crab shells with wound-healing properties is well known, as well as mitlan (a glycoprotein from mussels) that provides skin nutrition and promotes the resolution of skin scars. Far Eastern researchers [43, 40] used tinrostim for the treatment of purulent wounds of various genesis (Patent RF 2222337).

Tinrostim has been sufficiently well studied, and its preclinical trials have been conducted [17, 18]. In 1991, V.V. Yushkov [147] described the anti-inflammatory action of tinrostim.

The conducted studies served as the basis for the development of a new wound-healing agent — a chitosan gel with 0.1% tinrostim, manufactured as the "Ocean Balm" series (Registration Certificate No. 77-99.15.915 D.002225.04.05 dated 27.04.2005), the effectiveness of which was investigated during the course of the present work.

Currently, at the State Institute of Standardization and Control named after L.A. Tarashevich, documentation is being prepared for tinrostim for its registration as a pharmaceutical form.

The primary target of tinrostim application is phagocytes (macrophages and PMNs) involved in the processes of wound surface healing [93, 175].

The emergence of new immunotropic agents of peptide nature in the arsenal of clinicians expands the possibilities for correction of postoperative immunodeficiency, improvement of tissue repair, reduction of the number of complications, and mortality. Aim of the research:

To study the effectiveness of a gel containing chitosan and tinrostim in the comprehensive treatment of postoperative wounds and its influence on the frequency of infectious and inflammatory complications in proctological patients.

Research objectives:

1. To evaluate the effectiveness of a gel based on chitosan and tinrostim in various models of postoperative wounds in experiments on rats.

2. To study the dynamics of the morphological and cytological wound picture during the use of a chitosan gel with tinrostim compared with levomecetin/methyluracil ointment.

3. To compare the results of treatment of proctological patients using the standard patient management methodology with the results of using a chitosan gel with tinrostim in the comprehensive treatment.

4. To develop and implement in clinical practice an algorithm of therapeutic tactics for postoperative perineal wounds using a chitosan gel with tinrostim.

Scientific novelty

For the first time, an experimental and clinical study of the effectiveness of biopolymers from marine hydrobionts in the composition of a chitosan gel with tinrostim for local treatment of postoperative wounds has been conducted.

For the first time, the dynamics of postoperative wound healing, the histological picture of tissues in experiments on rats, against the background of using a gel based on chitosan containing tinrostim, has been studied.

Based on dynamic morphological and planimetric monitoring of wound healing in experimental animals, it has been established that the best results are achieved when treating wounds with a gel containing 0.1% tinrostim: reduction in wound surface area, earlier appearance of epithelioid cells, and active formation of granulation tissue.

Practical significance of the work

The effectiveness of a gel containing tinrostim in the treatment of postoperative perineal wounds in colorectal surgery and the prevention of postoperative complications has been established.

It has been shown that the use of a chitosan gel with tinrostim in proctological patients with a complicated disease course significantly improves tissue repair processes, reduces the frequency of infectious and inflammatory complications by 10%, and reduces the hospital stay period by 2.32 ± 0.22 days.

A priority certificate was obtained for the "Method of influencing the wound process with biopolymers in colorectal surgery" No. 2633 dated December 15, 2005.

A patent application has been filed for the method of treating postoperative perineal wounds in patients with colorectal pathology.

Main provisions for defense

1. The possibility of clinical application of a chitosan gel with tinrostim in the comprehensive treatment of patients with postoperative perineal wounds has been experimentally substantiated.

2. The inclusion of a gel containing tinrostim in the comprehensive treatment of postoperative wounds in proctological patients reduces the activity of the inflammatory response, improves reparative processes through active granulation tissue formation, and accelerates epithelialization and wound scarring.

3. When using a chitosan gel with tinrostim in the postoperative period in proctological patients, wound cleansing and healing, the second phase of the wound process, occur significantly earlier, and postoperative wound healing proceeds with significantly fewer complications (30.8%) compared with traditional therapy (50%) (levomecetin/methyluracil ointment).

4. The use of a gel containing tinrostim in the comprehensive treatment of proctological patients makes it possible to reduce their hospital stay by 2.15 ± 0.05 days and reduce the duration of outpatient treatment by 2.09 ± 0.29 days, and improve functional treatment outcomes monitored over a period of 2 to 8 months.

Presentation and implementation of research results

The dissertation materials have been presented and reported at scientific forums of national and regional levels:

- II Regional Far Eastern Congress "Man and Medicine," with international participation (Vladivostok, 2005);

- I Congress of Surgeons of Siberia and the Far East (Ulan-Ude, 2005),

- Scientific and Practical Conference of Coloproctologists and Surgeons of the Far Eastern and Siberian Federal Districts (Blagoveshchensk, 2005);

- VII Pacific Scientific and Practical Conference of Students and Young Scientists with international participation (Vladivostok, 2006).

The dissertation work was presented for review at the meeting of the problem commission "Surgery of the Abdominal Organs and Other Questions of Surgery" of the State Educational Institution of Higher Professional Education Vladivostok State Medical University (Vladivostok, May 2006).

Methodological recommendations entitled "Use of a chitosan gel with 0.1% tinrostim in the prevention and comprehensive treatment of proctological patients with postoperative perineal wounds" have been developed and implemented in practice for surgeons and coloproctologists.

The materials of the work are used by physicians in the comprehensive set of preventive and therapeutic measures for proctological patients at the coloproctology center of the Primorsky Regional Clinical Hospital No. 1, Vladivostok, and in the educational process for students, clinical residents, and physicians training at the Department of Hospital Surgery with a Continuing Medical Education Course of the State Educational Institution of Higher Professional Education Vladivostok State Medical University, Roszdrav.

Publications

Seven printed works have been published on the topic of the dissertation. Volume and structure of the dissertation