RU2774440C1 - Means for the treatment of purulent-inflammatory processes of soft tissues and mucous membranes. - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to the field of medicine and the pharmaceutical industry, namely to surgery, dermatology, obstetrics and gynecology, otorhinolaryngology, and is intended for the treatment of pyoinflammatory processes of soft tissues and mucous membranes. An agent for the treatment of purulent-inflammatory processes of soft tissues and mucous membranes is an ointment and contains a combination of the antiseptic hexetidine and the photosensitizer photoditazine as therapeutic components, and methylcellulose as the basis. Components are used in the declared quantities.

EFFECT: use of the invention provides an effective antimicrobial, sorption and wound healing effect.

1 cl, 3 tbl, 2 ex

Description

The invention relates to medicine and the pharmaceutical industry, namely to agents having antimicrobial, sorption and wound healing effects on local pyoinflammatory processes of soft tissues and mucous membranes used in surgery, dermatology, obstetrics and gynecology, otorhinolaryngology.

Relevance of the topic. An actual problem in surgery is the occurrence, prevention and methods of combating infectious complications of wounds. 30-35% of all surgical diseases are purulent complications, and in the surgical clinic, wound suppuration in the structure of hospital infection is 11-62.2%. Along with this, about 42% of deaths after surgical interventions are associated with pyoinflammatory complications.

There is a huge range of methods for the treatment of purulent wounds, as well as new methods for the treatment of purulent wounds are being developed and implemented, the use of the method of treating wounds under a bandage is today the main one due to its availability, ease of use and economic benefits.

Antibiotic therapy occupies a leading place in the complex of measures for the prevention and treatment of wound infection. However, its widespread and irrational use has led to the emergence of antibiotic-resistant and antibiotic-dependent forms of microorganisms, changes in reactivity and a decrease in the body's immunological forces. And as a result, the balance between the body's defenses and the virulence of the invading flora was disturbed, the clinic of the suppuration process also changed and the number of generalized forms of purulent infection and the number of suppuration of postoperative wounds increased.

In this regard, there is currently a growing interest in antiseptics, which are widely known and have proven themselves in the treatment of local pyoinflammatory processes in surgical practice. But at the same time, antiseptics require a rather long use, which delays the process of wound healing and the period of temporary disability of the patient. The use of photosensitizers today is also being actively introduced into the practice of a surgical doctor precisely in the aspect of local treatment of purulent wounds, photosensitizers accelerate reparative processes and reduce hospitalization time.

The prototype of our invention is an agent for the treatment of purulent wounds in the form of an aqueous gel, including dimethylglucamine salt of chlorin E6 and a biosoluble polymer, which is a mixture of Pluronic F127 and sodium salt of carboxymethyl cellulose, and it additionally contains hydroxyapatite nanoparticles (RF Patent No. 2530589 "Means for the treatment of purulent wounds , the method of obtaining it and the method of treating purulent wounds")

However, this tool is a hydrogel, which does not have a direct antimicrobial effect.

The technical result of the invention is the creation of an effective agent in the form of an ointment with antimicrobial, sorption, wound healing effects.

The technical result is achieved by the fact that the agent for the treatment of pyoinflammatory processes of soft tissues and mucous membranes is an ointment and contains a combination of the antiseptic hexetidine and the photosensitizer photoditazine as a therapeutic component, and methylcellulose as the basis in the following mass fractions:

Photoditazine 1.0 (ND 001246-010817) Hexetidine 0.5 (ND 42-59737) Methylcellulose 2.0 (FS 9004-67-5) Purified water up to 100.0 (FS 42-2619-97)

Characteristics of objects:

Photoditazine - belongs to the photosensitizers of the second generation. Designed for photodynamic therapy in the treatment of various diseases or fluorescent diagnostics. It is most often used in the treatment of malignant tumors, especially squamous cell skin cancer. Recently, it has been used in the treatment of purulent-inflammatory processes of soft tissues, it accelerates the reparative processes of soft tissues. After the penetration of photoditazin into the pathogenic cell, it is located inside the membrane or cytoplasm; during a phototherapy session, it begins to absorb a quantum of laser radiation and goes into a singlet (excited) state. To achieve the maximum effect of the drug, irradiation with monochromatic light with a wavelength of 662 nm is necessary.

Hexetidine - is a drug in the form of a solution or aerosol. Belongs to the group of antiseptics and has a wide spectrum of antibacterial and antimicrobial action. Hexetidine has a destructive effect on the cell membrane of microorganisms or disrupts the metabolism of pathogenic microflora, thereby exerting a bactericidal effect against fungi of the genus Candida - it prevents the formation of compounds that form the shell of the fungus. It is a thiamine antagonist. It has good adhesive properties. It is most often used for diseases of the oral cavity requiring antibiotics.

Methylcellulose is a synthetic polymer. Represents the hydrophilic white powder which is dissolved in cold water, forming transparent or translucent gel. The use of methylcellulose in ointments increases their hydrophilicity, accelerates the release of active substances from the drug, and also improves the contactability of the drug and the affected area of the skin.

Purified water is a liquid that has no color, taste or smell. Water was used as a solvent.

THE METHOD IS CARRIED OUT AS FOLLOWS

The technology was carried out under aseptic conditions and included two stages:

1. Preparation of a polymer solution. A weighed portion of methylcellulose in a sterile glass stand was poured with half the amount of sterile purified water heated to a temperature of (80-90)°C, gently mixed, and placed in a refrigerator (4±1)°C to swell and dissolve the polymer.

2. The introduction of medicinal substances. Hexetidine and photoditazine were dissolved in the remaining amount of sterile purified water. The resulting solution of medicinal substances was added to the polymer solution, homogenized by gentle stirring until a homogeneous mass was formed.

EXAMPLE BY PRODUCTION METHOD

1. Preparation of a polymer solution. A weighed portion of methylcellulose (2.0 mass fractions) in a sterile glass stand was poured with half the amount of sterile purified water heated to a temperature of (80-90)°C, gently mixed, and placed in a refrigerator (4 ± 1)°C to swell and dissolve the polymer.

2. The introduction of medicinal substances. Hexetidine (0.5 mass fractions) and photoditazine (1.0 mass fractions) were dissolved in the remaining amount of sterile purified water. The resulting solution of medicinal substances was added to the polymer solution, homogenized by gentle stirring until a homogeneous mass was formed.

EXAMPLE OF EXPERIMENTAL APPLICATION

The study of the wound healing activity of the developed agent was carried out in an experiment on male rats of the Wistar breed, weighing 180-200 g, in which a purulent wound was modeled according to the method of P.I. Tolstykh. The experimental animals were divided into two groups, 30 animals in each:

In the 1st group (model) treatment was not carried out.

In the 2nd group (experimental) were treated with the tool developed by us.

The course of the wound process in experimental animals was assessed by planimetric (L.I. Popova's method), microbiological, and histological methods. All data were subjected to statistical processing, the median, 25th and 75th percentiles were calculated (Me (25; 75)). Reliability was assessed using the Mann-Whitney test. Differences were considered statistically significant at p<0.05.

The animals were taken out of the experiment on the 3rd, 5th, 8th, 10th days.

48 hours after the modeling of a purulent wound in all groups, the wounds looked as follows: the bottom of the wound was covered with a layer of fibrin, small areas of necrosis, purulent-hemorrhagic discharge, pronounced perifocal edema.

Throughout the treatment process, a gradual change in the appearance of the simulated purulent wound occurred: the amount of purulent discharge from the wound decreased; the swelling of the soft tissues surrounding the wound went away; the bottom of the wound was covered with granulations, marginal epithelialization began, and a gradual complete cleansing of the wound took place.

The data of the planimetric study indicate a faster decrease in the area of wounds in the experimental group compared to the model (the initial area of the wounds was 251±2.55 mm ² ). The results of the planimetric study are presented in Table. 1 and 2.

Table 1

Dynamics of the percentage decrease in the area of wounds (%), Me (25; 75)

Group Model Experienced 3 days (n=30) 4.1
(2.2; 5.7) 33.2
(25.4; 29.2) ^* 5 days (n=24) 9.2
(8; 11.5) 59
(55; 62) ^* 8 days (n=18) 20.3
(18.5; 21.5) 80.5
(75.5; 82.9) ^* 10 days (n=12) 34.6
(32.8; 35.9) 95.2
(94.7; 95.6) ^*

Note: * - p<0.05 when comparing groups.

table 2

Dynamics of healing rate (CV) of wounds during treatment, Me (25;75)

NW,
%/day Groups Model Experienced 1-3 days
(n=30) 2 (1.1;2.8) 16.6 (12.7; 19.6)* 3-5 days
(n=24) 2.6 (1.7; 3.6) 12.5 (9.6; 16.7)* 5-8 days
(n=18) 3.4 (2.6; 4.5) 7.6 (4.6; 8.2)* 8-10 days
(n=12) 6.9 (6.1; 7.7) 7.8 (6.2; 10.2)

Note: * - p<0.05 when comparing groups.

Thus, the obtained data of the planimetric study confirm the high efficiency of the agent developed by us (experimental group) in the treatment of purulent wounds. By the 15th day, the area of wounds in the experimental group decreased by an average of 95.2%, which is on average 2.75 times more than in the model group. In addition, in the experimental group, the SZ of wounds was maximum in the first phase of the wound process (1-5 days) and significantly exceeded this indicator of the model group.

The data of the microbiological study (Table 3) showed that in the experimental group, the microbial contamination of wounds was significantly less than in the model group, starting from the 3rd day and throughout the entire observation period. In the experimental group on the 10th day, the microbial contamination of wounds is more than 15,000 times less than in the model group.

Table 3

Dynamics of microbial contamination of wounds, CFU/g, Me (25; 75)

Group Model Experienced 3 days 4.9
(4.8; 5.1) x10 ⁷ 4.3
(4.1; 4.3) x10 ^{5 *} 5 days 4.5
(4.3; 4.7) x10 ⁷ 4.4
(4.2; 4.5) x10 ^{3 *} 8 days 4.6
(4.4; 4.6) x10 ⁶ 2.1 (1.9; 2.2) x10 ^{3 *} 10 days 3.8 (3.7; 3.9) x10 ⁶ 2.4 (2.2; 2.5) x10 ^{2 *}

Note: * - p<0.05 when comparing groups.

For a complete assessment of the state of the wound in dynamics, a histological method was used to study wound biopsy specimens, which makes it possible to objectively assess the dynamics of the course of the wound process.

In all the studied groups, on the fifth day, a leukocyte wall was formed, which distinguished between necrotic and granulation tissue. Thus, in the model group, the maximum amount of necrotic tissue was observed. In the experimental group, by this time, an extensive zone covered with granulations had formed, the regenerating epithelium covered a third of the entire granulation tissue. In addition, blood capillaries were visualized, thanks to which the process of neoangiogenesis began and proceeded actively.

On the 10th day of treatment of a purulent wound, almost complete replacement of the wound defect up to the papillary dermis layer was observed with a high degree of granulation tissue with a maximum severity in the experimental group. Complete epithelialization of the wound was observed in the experimental group, and there was no model in the group. So, in the model group, the wound defect was only half filled with granulations, while there was a clear predominance of inflammatory cells. In the experimental group, it was noted that the newly formed epithelium was thin, there was no pronounced stratum corneum, and its area was more than 70% of the wound area.

Thus, the use of the developed agent in the treatment of purulent wounds in phases I and II of the wound process increases the rate of wound healing, reduces the microbial contamination of wounds, accelerates the formation and maturation of granulation tissue, and promotes early and rapid epithelialization of the wound surface.

Claims (3)

An agent for the treatment of purulent-inflammatory processes of soft tissues and mucous membranes is an ointment and contains a combination of the antiseptic hexetidine and the photosensitizer photoditazine as a therapeutic component, and methylcellulose as the basis in the following mass fractions: Photoditazine 1.0 Hexetidine 0.5 Methylcellulose 2.0 Purified water up to 100.0