RU2326667C1 - Medicinal agent for treatment of suppurative-inflammatory skin and soft tissue diseases of different aetiology - Google Patents

Abstract

FIELD: medicine; pharmacology.

SUBSTANCE: agent contains antibacterial substance of fluoroquinolones, hydrophilic base and optionally at least one adjuvant. As hydrophilic base agent contains silicone glycerohydrogel of composition Si(C₃H₇O₃)4 · xC₃H₈O₃ · yH₂O, where 3 ≤ x ≤ 10, 20 ≤ y ≤40. As antibacterial substance of fluoroquinolones agent contains perphloxacyn, ophloxacyn, cyprophloxacyn, norphloxacyn, lomephloxacyn, moxyphloxacyn, csparphloxacyn or enoxacyn. Agent can contain as adjuvant chlorhexidine bigluconate, lydocaine hydrochloride, sea-buckthorn oil, brier oil or mixture. New agent for treatment of suppurative-inflammatory skin and soft tissues diseases including decubitus ulcers, burns, trophic ulcer, has high antibacterial effect due to wide antibacterial action (fluoroquinolones) and high transcutaneous and anti-edematous activity (silicone glycerohydrogel), and do not carry negative by-effects.

EFFECT: agent is stable, easy for keeping and well wipe-off.

6 cl, 5 dwg, 3 tbl, 6 ex

Description

The invention relates to the pharmaceutical industry and medicine and relates to a wound healing topical drug for the treatment of purulent-inflammatory diseases of the skin and soft tissues of various etiologies, including pressure sores, burns, long-healing wounds, trophic ulcers.

In the treatment of purulent-inflammatory diseases of the skin, soft tissues and mucous membranes, local treatment is often used along with systemic treatment: in some cases it is not only necessary, but also the only possible one.

There is a whole arsenal of drugs used in the local treatment of purulent infections, nevertheless, the problem of increasing the effectiveness of treatment and reducing its duration remains relevant.

Of particular interest in the treatment of purulent-inflammatory diseases of the skin and soft tissues of various etiologies are antibacterial substances of a number of fluoroquinolones - pefloxacin, ciprofloxacin, ofloxacin, norfloxacin and others [Mashkovsky MD Medicines M .: "New Wave", 2005. - c.844].

They are active against most gram-negative bacteria (Pseudomonas aeruginosa, Haemophilus influenzae and Escherichia coli, Shigella, Salmonella, Meningococci, some varieties of pneumococci, gonococci), many strains of staphylococci, as well as Campylobacter, Legionella, Mycoplasma, Chlamydia. Currently, in medical practice, fluoroquinolones are prescribed mainly orally or parenterally, the use of local treatment is negligible.

It is known to use fluoroquinolones (ofloxacin, ciprofloxacin, norfloxacin) for topical treatment of ulcerative defects, in particular aphthous ulcers that occur on the oral mucosa (US patent 5686095, MKI A61K 31/496, 1997). Fluoroquinolones are used in the form of a solution, paste, ointment or gel, preferably applied three to eight times a day until the ulcerative defect disappears. Topical use of fluoroquinolones allows the use of lower doses to achieve a satisfactory concentration of fluoroquinolone in the ulcer area, thereby minimizing the likelihood of side effects that can occur with systemic administration.

However, the disadvantages of the known funds include a narrow spectrum of use and the need for frequent (up to eight times a day) application to the affected areas due to insufficient penetrating activity of the agent.

Known topical agent for the treatment of acne and other bacterial skin lesions, including the antibacterial substance of a number of fluoroquinolones (ofloxacin, ciprofloxacin, norfloxacin, enoxacin, cinoxacin, pefloxacin, lomefloxacin, fleroxacin, tosufloxacin, temafloxacin and benzofloxacin bisofloxacin U.S. Patent 5912255, MKI A61K 31/47, 1999). The product can be used in the form of a cream, ointment, lotion, gel, suspension, emulsion, spray and transdermal system, while fluoroquinolones with benzoyl peroxide create a synergistic pair that increases the effectiveness of the product, the concentration of fluoroquinolones in the product is 5-10%, benzoyl peroxide - 2-10%. The tool in various forms is made on a hydrophilic basis on the basis of hydroxypropyl cellulose, polyethylene glycol-400, propylene glycol and alcohol.

However, the disadvantages of the known funds should include a narrow range of use of the tool. In addition, the presence of a sufficiently large amount of alcohol (according to the examples given) can lead to irritation of the affected areas of the skin and its drying.

Closest to the proposed invention is a tool for topical treatment of skin diseases of various etiologies (including infected and inflammatory lesions), containing an antibacterial substance of a number of fluoroquinolones (ofloxacin, ciprofloxacin, norfloxacin, enoxacin, cinoxacin, pefloxacin, lomefloxacin, fleroxacin, tosofloxacin and temofloxacin and temofloxacin and difloxacin) in a concentration of 5-10 wt.% on a mixed alcohol-acetone hydrophilic base containing hydroxypropyl cellulose, polyethylene glycol-400 and propylene glycol (US patent 6017912, MKI AK61K 031/535, 2000) (prototype). The tool can be used in the form of a cream, ointment, lotion, gel, suspension, emulsion, tincture, spray and transdermal system. Known tool has increased transcutaneous activity due to the presence in its composition of a transdermal conductor - a mixture of alcohol and acetone.

A disadvantage of the known means is the use in its composition of a mixture of alcohol and acetone, which can lead to adverse consequences due to irritation and drying of the skin. In addition, acetone can have a negative side effect: cause itchy dermatitis, impaired liver and kidney function.

Thus, the authors were faced with the task of developing a tool with a wide spectrum of action for topical application - wound healing, antimicrobial, anti-inflammatory, antioxidant, without adverse side effects, with minimal contraindications for use.

The problem is solved by using the proposed means for the treatment of purulent-inflammatory diseases of the skin and soft tissues of various etiologies, containing an antibacterial substance of a number of fluoroquinolones, a hydrophilic base and optionally at least one auxiliary substance, which contains organosilicon glyceride hydrogel Si (C ₃ H ₇ O ₃ ) ₄ · xC ₃ H ₈ O ₃ · yN ₂ O, where 3≤x≤10, 20≤y≤40, in the following ratio of components, wt.%:

antibacterial substance series - 0.5 ÷ 1.0 fluoroquinolones excipient - 0.0 ÷ 7.0 organosilicon glycerohydrogel Si (C ₃ H ₇ O ₃ ) ₄ · xC ₃ H ₈ O ₃ · yN ₂ O, where 3≤x≤10, 20≤y≤40 - the rest is up to 100,

The proposed agent may contain a number of fluoroquinolones pefloxacin, ofloxacin, ciprofloxacin, norfloxacin, lomefloxacin, levofloxacin, moxifloxacin, sparfloxacin and enoxacin as an antibacterial substance.

The proposed tool may contain as an auxiliary substance chlorhexidine bigluconate, lidocaine hydrochloride, sea buckthorn oil, rose hip or a mixture thereof.

Currently, in the scientific, technical and patent literature, it is not known a means for the treatment of purulent-inflammatory diseases of the skin and soft tissues, containing as a hydrophilic base an organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · xC ₂ H ₈ O ₃ · yN ₂ O, where 3≤x≤10, 20≤y≤40, and also characterized by the combination of the proposed components in the claimed limits of their content.

The fluoroquinolones used in the proposed agent are commercial preparations widely used in the treatment of various bacterial infections. Fluoroquinolones appear to be effective against Staphylococcus aureus, Streptococcus pneumoniae, coagulese-negative staphylococci, Streptococcus pyogenes, Staphylococcus epidermis, Pseudomonas aeruginosa, Eschcrichia coli, Citrobacteribromus fibrusella, Klebsiella citrusella and other microorganisms.

In the proposed tool as a hydrophilic base use organosilicon glycerohydrogel composition Si (C ₃ H ₇ O ₃ ) ₄ · xC ₃ H ₈ O ₃ · yH ₂ O, where 3≤x≤10, 20≤y≤40 (RF patent 2255939, MKI C07F 7/04, 2005), which has a set of positive properties: high transcutaneous and decongestant activity, a wound healing effect, favorably affecting the processes of epithelization, is non-toxic. Transcutaneous gel activity leads to a significant decrease in the concentration of the active substance - fluoroquinolone - in the tool (compared with the prototype).

Studies conducted by the authors showed good compatibility of two active components: fluoroquinolones and organosilicon glycerohydrogel and to reveal the limits of their quantitative content in the composition, providing the manifestation of the maximum therapeutic effect. So, when the fluoroquinolone content is less than 0.5 wt.%, A slowdown in the manifestation of the therapeutic effect is observed. When the fluoroquinolone content is more than 1.0 wt.%, The effectiveness of the agent practically does not increase (the difference in performance is unreliable).

As auxiliary substances can be used: chlorhexidine bigluconate (antiseptic), lidocaine hydrochloride (anesthetic), sea buckthorn oil, rose hip (wound healing agents) or a mixture thereof.

The content of chlorhexidine bigluconate is 0.001-0.01 wt.%, The content of lidocaine hydrochloride is 0.5-1.0 wt.%, The oil content of sea buckthorn or wild rose is 5.0-7.0 wt.%.

The indicated concentration limits are optimal. Below these limits, the effectiveness of the components is significantly reduced. Increasing the concentration of the above limit is also impractical: in the case of chlorhexidine, a negative effect on the morphological parameters of the skin (affecting the formation of the scar) is possible; for sea buckthorn or rosehip oil, compatibility with the base deteriorates: higher concentrations of lidocaine hydrochloride are already used for anesthesia.

The proposed tool can be obtained as follows. Take organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · xC ₃ H ₈ O ₃ · yH ₂ O, where 3≤x≤10, 20≤y≤40 (RF patent 2255939, MKI C07F 7/04, 2005 ), which is a transparent or translucent colorless gel, odorless, stable during storage, easily washed off with water. Powder of an antibacterial substance of a number of fluoroquinolones (perfloxacin, ofloxacin, ciprofloxacin, norfloxacin, lomefloxacin, levofloxacin, moxifloxacin, sparfloxacin or enoxacin) is added with a particle size of 2-5 μm with a mass ratio of organosilicon glycerol hydrogol: 99: 1: 0: ,5. If necessary, chlorhexidine bigluconate, lidocaine hydrochloride, sea buckthorn, rosehip oil or a mixture thereof are also added in an amount not exceeding 7.0 wt.% In the composition. The mixture is thoroughly mixed at room temperature for 10-20 minutes in a rotary mixer. A yellow ointment of various shades is obtained, a soft consistency, the certification of which is carried out by a chemical-analytical method.

The proposed technical solution is illustrated by the following examples.

Example 1. Take organosilicon glycerohydrogel composition Si (C ₃ H ₇ O ₃ ) ₄ · 3C ₃ H ₈ About ₃ · 20H ₂ O, which is a translucent colorless gel, odorless, stable during storage. Pefloxacin powder with a particle size of 2-5 μm is added at a weight ratio of organosilicon glycerohydrogel: pefloxacin equal to 99: 1. The mixture is thoroughly mixed in a rotary type mixer at room temperature for 10-15 minutes. A ready-to-use ointment of light yellow color is obtained in the following ratio of components, wt.%: Pefloxacin - 1.0; organosilicon glycerohydrogel - 99.0; which meets the requirements for a topical pharmaceutical product.

Example 2. Take organosilicon glycerohydrogel composition Si (C ₃ H ₇ O ₃ ) ₄ · 10C ₃ H ₈ About ₃ · 40H ₂ O, which is a translucent colorless gel, odorless, stable during storage. Ciprofloxacin powder with a particle size of 2-5 μm was added at a weight ratio of organosilicon glycerohydrogel: ciprofloxacin equal to 99.5: 0.5. The mixture is thoroughly mixed at room temperature in a rotary tin mixer for 10-15 minutes. A ready-to-use ointment of light yellow color is obtained in the following ratio of components, wt.%: Ciprofloxacin - 0.5; organosilicon glycerohydrogel - 99.5; which meets the requirements for a topical pharmaceutical product.

Example 3. Take organosilicon glycerohydrogel composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ About ₃ · 24H ₂ O, which is a translucent colorless gel, odorless, stable during storage. Ofloxacin powder with a particle size of 2-5 μm is added at a mass ratio of organosilicon glycerohydrogel: ofloxacin equal to 99: 1. The mixture is thoroughly mixed in a rotary type mixer at room temperature for 10-15 minutes. A ready-to-use ointment of light yellow color is obtained in the following ratio of components, wt.%: Ofloxacin - 1.0; organosilicon glycerohydrogel - 99.0; which meets the requirements for a topical pharmaceutical product.

Example 4. Take organosilicon glycerohydrogel composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ O ₃ · 24H ₂ O, which is a translucent colorless gel, odorless, stable during storage. Ciprofloxacin powder with a particle size of 2-5 μm and lidocaine hydrochloride is added at a mass ratio of organosilicon glycerohydrogel: ciprofloxacin: lidocaine hydrochloride equal to 98: 1: 1. The mixture is thoroughly stirred at room temperature for 10-15 minutes. A ready-to-use ointment of light yellow color is obtained in the following ratio with the component, wt.%: Ciprofloxacin - 1.0; lidocaine hydrochloride - 1.0; organosilicon glycerohydrogel - 98.0; which meets the requirements for a topical pharmaceutical product.

Example 5. Take organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ O ₃ · 24 H ₂ O, which is a translucent colorless gel, odorless, stable during storage, Pefloxacin powder with a particle size of 2- is added 5 μm and chlorhexidine bigluconate with a mass ratio of organosilicon glycerohydrogel: pefloxacin: chlorhexidine bigluconate equal to 99.49: 0.5: 0.01. The mixture is thoroughly mixed at room temperature in a rotary mixer for 10-15 minutes. A ready-to-use ointment of light yellow color is obtained in the following ratio of components, wt.%: Pefloxacin - 0.5; chlorhexidine bigluconate - 0.01; organosilicon glycerohydrogel - 99.49; which meets the requirements for a topical pharmaceutical product.

Example 6. Take organosilicon glycerohydrogel composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₇ O ₃ · 24H ₂ O, which is a translucent colorless gel, odorless, stable during storage. Pefloxacin powder with a particle size of 2-5 μm and a mixture of sea buckthorn oil and rosehip oil, taken in equal amounts, are added in a mass ratio of organosilicon glycerohydrogel: pefloxacin: sea buckthorn oil and rosehip oil equal to 94.5: 0.5: 5.0. The mixture is thoroughly stirred at room temperature for 15-20 minutes. A ready-to-use amber-yellow ointment is obtained in the following ratio of components, wt.%: Pefloxacin - 0.5; a mixture of sea buckthorn oil and rosehip oil - 5.0: organosilicon glycerohydrogel - 94.5; which meets the requirements for a topical pharmaceutical product.

The antibacterial and wound healing properties of the agent obtained in the form of an ointment were evaluated.

Evaluation of the antibacterial properties of experimental samples of the proposed tool

The studies were performed at the Center for Military-Technical Problems of Biological Protection, Research Institute of Microbiology, Ministry of Defense of the Russian Federation.

In order to study the antibacterial properties of the new compositions, as well as to select the optimal concentration of the active drug additive - fluoroquinolone - in organosilicon glycerohydrogel, we studied the effects of experimental samples of 1% ointments containing pefloxacin and ciprofloxacin on an organosilicon basis of Si composition (Si ₃ C ₇ O ₃ ) ₄ · 6С ₃ Н ₈ О ₃ · 24Н ₂ O in relation to 5 bacterial strains that are causative agents of intestinal, urogenital, skin and some other human diseases.

The activity of the experimental samples was tested against test cultures of gram-negative and gram-positive bacteria and one representative from the Candida genus recommended for evaluating the activity of antibiotic preparations: Staphylococcus aureus 209 P ATCC 65, Pseudomonas aeruginosa ATCC 9026, Escherihia coli 25922, Salmonella typhimurium 55, Candida alb No. 690.

Culture strains obtained from the museum collection of the State Institute of Standardization and Control. L.A. Tarasevich.

Test cultures were grown at a temperature of 37 ° C for 18-24 hours on beveled meat-pentone agar.

An experimental sample of an ointment containing 1% pefloxacin was resuspended in water for injection in certain proportions, creating 0.01; 0.05 and 0.1% concentration. An experimental sample of an ointment containing 1% ciprofloxacin was investigated at concentrations: 0.005; 0.01; 0.05; 0.1 and 0.5%.

The antimicrobial activity of the samples was determined in accordance with the Guidelines for the study of the antimicrobial activity of pharmacological substances and the Guidelines for the study of the antifungal activity of pharmacological substances according to the Guidelines for the experimental (preclinical) study of new pharmacological substances.

The antibacterial effect of the experimental samples was evaluated by two methods:

by serial dilution of liquid bacterial cultures to determine the minimum inhibitory concentration - MIC, that is, the minimum concentration of the drug that inhibits the growth of microorganisms (for ointment containing pefloxacin);

diffusion method, based on the ability of antibiotic substances to diffuse from the holes cut in the thickness of the agar (for ointments containing pefloxacin and ciprofloxacin).

In the first case, experimental systems were created, which were microbial suspensions of test cultures on Hottinger medium containing colony forming cells (cells) at a concentration of 1 · 10 ⁵ cells. cm ^-3 , and resuscitated preparations of an experimental sample of an ointment containing pefloxacin. An indication of the effect of the drug on test strains was a change in turbidity in test tubes after 18-20 hours of incubation at 37 ° C, indicating the presence or absence of growth and reproduction of microorganisms. For comparison, the antibacterial activity of the commercial drug pefloxacin was evaluated at the same concentrations in water for injection. As a control, systems that did not contain an active component were used.

At the same time, to confirm the bactericidal effect of the experimental sample in relation to test cultures, the concentration of viable cells was calculated by plating on plates with Hottinger agar and determining the number of colony forming units (CFU) in experimental and control tubes. The results of the study of ointments containing pefloxacin are presented in tables 1 and 2.

The study of the sensitivity of test cultures from experimental systems in a liquid medium by the method of successive dilutions (Table 1) made it possible to establish quantitative indicators of the bactericidal action of an ointment containing pefloxacin.

Table 1
The effect of the experimental sample of ointment containing pefloxacin on the survival of test cultures Test culture The content of colony forming units, KOH · cm ^-3 when exposed experimental sample pefloxacin the control 0.01% 0.05% 0.1% 0.01% 0.05% 0.1% E.coli (1.2 ± 0.3) 10 ² single colonies no growth (0.7 ± 0.1) 10 ² no growth no growth (2.5 ± 0.5) 10 ⁸ P.aerugenosa (1.4 ± 0.4) 10 ⁷ (2.4 ± 0.2) 10 ³ single colonies (7.0 ± 0.5) 10 ⁶ (1.3 ± 0.3) 10 ³ no growth (1.5 ± 0.3) 10 ⁹ S.aureus (2.1 ± 0.2) 10 ⁵ (1.8 ± 0.5) 10 ³ (2.0 ± 0.4) 10 ³ (1.1 ± 0.3) 10 ⁵ (1.3 ± 0.4) 10 ³ (1.7 ± 0.4) 10 ² (8.4 ± 2.1) 10 ⁸ S.typhimurium (4.5 ± 0.8) 10 ⁸ (4.6 ± 1.2) 10 ⁵ (1.4 ± 0.2) 10 ³ (3.5 ± 0.5) 10 ⁸ (3.1 ± 0.8) 10 ⁵ (0.7 ± 0.3) 10 ³ (1.8 ± 10.3) 10 ⁸ C.albicans (2.0 ± 0.3) 10 ⁸ (2.4 ± 0.2) 10 ⁸ (2.1 ± 0.3) 10 ⁸ (1.0 ± 0.4) 10 ⁸ (1.6 ± 0.2) 10 ⁸ (1.8 ± 0.4) 10 ⁸ (2.3 ± 0.2) 10 ⁸

An assessment of the content of microorganisms revealed the fact of inhibition of the growth of sensitivity of cultures already at a concentration of the active principle in the gel of 0.01%. However, the C. albicans strain showed high resistance to the studied experimental sample at all tested concentrations.

When testing the effectiveness of an experimental sample of pefloxacin ointment using the diffusion method, the aforementioned dilutions of the gel composition in water for injection in an amount of 0.1 cm ³ were added to wells 8 mm in diameter prepared in advance in Hottinger agar, poured into Petri dishes. Around the wells along the radii of the agar plate were sown with strokes of the test culture and incubated for 48 hours at 37 ° C. Table 2 presents the results of determining the zones of growth inhibition of test cultures.

According to the data obtained, the analyzed dosage form has a pronounced antibacterial spectrum of action, covering aerobic bacterial forms of gram-positive and gram-negative conditionally pathogenic microorganisms, but does not affect the representative of the genus Candida. Among the studied strains, S. aureus and E. coli test cultures are highly sensitive; S. typhimurium and P. aerugenosa can be classified as medium-sensitive strains; C. albicans culture is resistant to the active ingredient.

Table 2.
The size of the zones of inhibition of growth of test cultures depending on the concentration of pefloxacin in the experimental sample Test strains The size of the zone of oppression, mm, at concentrations 0.01% 0.05% 0.1% E.coli 28.4 ± 1.2 > 35 > 35 P.aerugenosa 0 5.0 ± 0.3 13.0 ± 1.1 S.aureus 10.2 ± 2.1 16.0 ± 2.8 28.5 ± 1.4 S.typhimurium 11.0 ± 0.5 13.2 ± 0.8 15.3 ± 1.8 C.albicans 0 0 0

The drug at sufficiently low concentrations of pefloxacin already shows a pronounced activity against Escherichia coli, Salmonella, as well as test culture P.aerugenosa, starting from 0.01%, while exhibiting a bactericidal effect against gram-positive cocci, in particular S.aureus. There is only a slight decrease in the antibacterial activity of pefloxacin in the composition of the experimental sample compared to commercial pefloxacin in aqueous solution.

Table 3 presents data on the antimicrobial effect of an ointment containing ciprofloxacin.

Table 3
The size of the zones of inhibition of growth of test cultures depending on the concentration of ciprofloxacin in the experimental sample Bacterial cultures Growth retardation zone with various ciprofloxacin content, mm 0.5% 0.1% 0.05% 0.01% 0.005% E.coli more than 35.0 more than 35.0 more than 35.0 28.0 24.0 S.typhimurium 23.2 18.0 12.4 10.5 8.3 S.aureus 34.2 28.0 23.1 18.2 15.2 P.aerugenosa 17.0 13.0 8.1 5.2 5.0 C.albicans 0 0 0 0 0

In the case of an ointment containing ciprofloxacin, greater sensitivity to test cultures of P.aerugenosa and S.aureus can be noted. At the same time, a decrease in the antibacterial activity of ciprofloxacin in the composition of the experimental sample compared with the same concentrations of ciprofloxacin in aqueous solutions taken for comparison was not detected.

Thus, we can conclude that the studied samples of fluoroquinolone ointments containing pefloxacin and ciprofloxacin have pronounced antimicrobial activity against bacteria of the intestinal group, as well as gram-positive cocci, in particular S.aureus 209 P ATCC 6538, which has a high level of resistance to a wide spectrum antibiotics, The causative agent of candidiasis C.albicans IMV No. 690 is resistant to the analyzed dosage forms.

Comparative evaluation of the wound healing effect of the proposed tool

Studies performed at the Ural State Medical Academy

In this study, we evaluated the effect of an ointment containing 0.5% pefloxacin on the healing of thermal burns and mechanical injury in a comparative aspect with a composition containing 0.025% chlorhexidine bigluconate in organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ O ₃ · 24 H ₂ O. The experiment was performed on 90 white Vistar rats weighing 220-350 g. Rats were divided into 6 groups of 15 animals each. Two groups under ether rash anesthesia were subjected to a thermal burn of the II-III degree with an area of 40 × 60 mm using a metal plate heated to 100 ° C, after 30-second contact with the skin of the left side treated from wool. The two following groups also suffered a mechanical injury on their left side - a skin flap with an area of 20 × 20 mm was cut off. Two groups with burns and mechanical trauma remained control (without treatment). Preliminarily (a day before the injury), rats were recorded tentative research reactions in the "open field", re-registration was carried out a day after injuries, on the 6th and 15th day. The drugs were used topically: on the next day after injuring the skin, two groups with burns and mechanical trauma were applied with ointment containing pefloxacin; two other groups with a burn and mechanical trauma - the application of an ointment containing chlorhexidine. These compositions were applied to the affected areas of the skin every day in the morning for 0.5 g. After completion of the treatment, animals under ether rash anesthesia took blood from the cavities of the heart, visceral organs (heart, lungs, liver, spleen, adrenal glands, brain) and skin flaps with local burns and mechanical injuries, which were placed in a 10% formalin solution to fix them and assess the morphology of these tissues.

The dynamics of the mass of white rats

The mass of rats was monitored before injury and on the 15th day of the study before taking blood. In rats of all groups, the mass tended to increase. In the control groups, the increase in weight was unreliable and amounted to 9% (burn), 12% (mechanical injury), 13% (intact). A significant increase in weight was observed in the group "mechanical injury + ointment containing chlorhexidine" - 19%, "mechanical injury + ointment containing pefloxacin" - 44%; "burn + ointment containing pefloxacin" - by 54%.

The state of tentative research reactions of white rats

In the open-field study, the vertical and horizontal activity of animals was assessed according to the following indicators: time of departure from the central circle, number of squares traveled, number of steps on the hind legs (vertical uprights), washing and cleaning (grooming), peeping in holes (examination “norm ") For 3 minutes.

In the control groups, a decrease in horizontal and vertical activity, grooming and inspection of holes was observed, but compared with the initial level throughout the study (1, 6, 15 days after the injury). In all groups, on the 1st day, a decrease in activity was also noted for all indicators, especially expressed in groups with mechanical trauma. On the 6th day, a tendency toward restoration of activity appeared, but in most groups it remained below the initial level. On the 15th day of the study, the activity of animals in most experimental groups approached the initial level. Moreover, on the 15th day, the grooming process was the most active in the experimental groups of rats with burns and mechanical trauma during treatment with ointment containing pefloxacin, which confirms the high "quality of life" of the experimental animals (figure 1).

Thus, according to the dynamics of rat activity, we can conclude that the studied compositions based on organosilicon gel accelerate the healing of traumatic skin lesions. This is confirmed by visual assessment (figure 2 and 3).

The healing time of traumatic injuries in the control groups ranged from 15 to 21 days; in the treatment of ointments containing pefloxacin and chlorhexidine - 9-13 and 15-20 days, respectively.

Blood rats of white rats

After the completion of these studies, a general blood test was performed. An increase in hemoglobin levels was observed in the groups “burn + ointment containing chlorhexidine”, “burn + ointment containing pefloxacin”, “mechanical injury + ointment containing pefloxacin”; a decrease in the level of leukocytes in the group "mechanical trauma + ointment containing pefloxacin". Identified changes in indicators of blood cells are reflected in figures 4 and 5, which also indicates a positive therapeutic effect of the proposed drug.

Morphological studies of rat skin samples after treatment of burns and mechanical injuries

In the control groups with a burn model (without treatment), dystrophic changes in the epidermis were revealed, subepithelial cavities in the dermis against a background of pronounced edema with destruction of the collagen fibers of the papillary layer, NLS infiltration (segmented leukocytes), subcutaneous fat swelling.

Under the conditions of therapy with an ointment containing chlorhexidine, destructive and inflammatory changes persist, reaching the deep layers of the dermis and affecting the subcutaneous fat. Epithelization in the lesion area is incomplete, the epidermis without signs of reparative regeneration.

Against the background of the use of an ointment containing pefloxacin, the epidermis is restored throughout the lesion, with signs of proliferative activity of the epithelial cells of the basal layer. Edema, single subepithelial cavities, moderate diffuse lymphohistiocytic infiltration persist in the dermis, the depth of damage is limited to subcutaneous fat.

In the control groups with a model of mechanical trauma, skin damage is characterized by a greater depth and degree of destruction of the epidermis. Granulation tissue is determined in the wound canal, with hemorrhages, pronounced infiltration of SNL in the subcutaneous fat and striated muscle tissue - pronounced interstitial sclerosis.

When treating with an ointment containing chlorhexidine, the wound defect epithelization is incomplete, edema and destructive-inflammatory changes in the dermis, limited by its deep layers, are preserved.

The use of an ointment containing pefloxacin leads to complete epithelization of the damage zone. In the dermis, the wound swing was limited by its deep layers, represented by granulation and mature connective tissue, the nature of inflammatory infiltration is lymphohistiocytic. A more pronounced proliferative activity of cells of the stratified squamous epithelium over the damage zone was recorded.

Visceral organs - no change.

Thus, studies on experimental animals show that the use of an ointment containing pefloxacin at concentrations of 0.5% leads to a significant reduction in the treatment time (from 21 to 9 days) of thermal burns and mechanical injuries prone to infection. In this case, a positive effect is also noted for an ointment containing chlorhexidine, which can be used in the claimed agent as an auxiliary component, which has a short-term antiseptic effect. However, the ointment containing chlorhexidine is inferior to the ointment containing pefloxacin in terms of healing and quality of treatment, which is confirmed by morphological studies of damaged tissues.

Data from clinical studies on the use of the proposed agent for the treatment of purulent-inflammatory diseases of the skin and soft tissues in patient volunteers of the surgical department of the Sverdlovsk Regional Psychoneurological Hospital for war veterans are illustrated by the following examples, indicating the high effectiveness of the claimed agent.

Example 1. Patient S., 30 years old. with extensive pressure sores of the lumbosacral region and the hip joints. He entered the purulent surgery department on December 29, 2005. Against the background of general antibacterial and detoxification therapy, once a day, bedsores were lubricated with an ointment of the composition, wt.%: Pefloxacin - 1.0; organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ O ₃ · 24H ₂ O - 99.0. Complete cleansing and epithelialization occurred on the 7-8th day when using an ointment containing pefloxacin (0.5%) with rosehip oil (7%) at the last stage of treatment, especially in the area of wounds of large trochanter and for a longer time on the sacrum.

Example 2. Patient K., 60 years old. Diagnosis: diabetes mellitus, type 2, severe. Diabetic foot syndrome. Phlegmon rear moan right. Entered the purulent surgery department on March 1, 2005. On the same day, phlegmon dissection and drainage, necrectomy were performed. In the postoperative period, the wound was daily bandaged using an ointment composition, wt.%: Pefloxacin - 1.0; organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ O ₃ · 24H ₂ O - 99.0. The wound cleared on the 3rd day from the start of treatment. Complete healing occurred on the 12-13th day.

Example 3. Patient I., 27 years old, was operated on for a forearm abscess. After surgery for 7 days, an ointment of the composition was applied to the wound surface, wt.%: Pefloxacin - 1.0; organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ O ₃ · 24H ₂ O - 99.0. On the seventh day there was a complete healing of the wound surface.

Example 4. Patient S., 30 years old. Diagnosis: carbuncle of the interscapular region. He entered the purulent surgery department on the 6th day from the onset of the disease 06/20/2005. After preliminary preoperative preparation for the patient under intravenous anesthesia, the carbuncle of the back was excised, on the 8th phase of the wound process, the wound was dressed daily with an ointment, wt.%: Pefloxacin - 0.5; chlorhexidine bigluconate - 0.001; organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ O ₃ · 24H ₂ O — 99.499. Complete wound cleansing occurred on 2-3 days from the start of treatment.

Example 5. Patient S., 72 years old, was hospitalized with a diagnosis of trophic ulcer of the lower third of the left leg on the background of diabetes mellitus. With topical application of the ointment composition, wt.%: Ciprofloxacin - 1.0: lidocaine hydrochloride - 0.5; organosilicon glycerohydrogel of the composition Si (C ₃ H ₇ O ₃ ) ₄ · 6C ₃ H ₈ O ₃ · 24H ₂ O - 98.5; within three days, swelling decreased, fresh granulations appeared, and soreness decreased. There was a complete epithelization of the wound surface on the 12th day.

Thus, the proposed tool for the treatment of purulent-inflammatory diseases of the skin and soft tissues, including pressure sores, burns, trophic ulcers, has a high therapeutic effect due to a wide range of antibacterial action (fluoroquinolones) and a high level of transcutaneous and decongestant activity (organosilicon glycerohydrogel), it does not have any adverse side effects. In addition, the tool is characterized by stability, ease of storage, good washability.

Claims (6)

1. An agent for the treatment of purulent-inflammatory diseases of the skin and soft tissues of various etiologies, containing an antibacterial substance of a number of fluoroquinolones, a hydrophilic base and optionally at least one auxiliary substance, characterized in that it contains an organosilicon glyceride hydrogel Si composition (C ₃ H ₇ O ₃ ) ₄ · xC ₃ H ₈ O ₃ · yN ₂ O, where 3≤x≤10, 20≤y≤40 in the following ratio of components, wt.%: antibacterial substance series 0.5 ÷ 1.0 fluoroquinolone excipient 0,0 ÷ 7,0 organosilicon glycerohydro gel composition Si (C ₃ H ₇ O ₃ ) ₄ · xC ₃ H ₈ O ₃ · yN ₂ O, where 3≤x≤10, 20≤y≤40 the rest is up to 100 2. The tool according to claim 1, characterized in that it contains a number of fluoroquinolones pefloxacin, ofloxacin, ciprofloxacin, norfloxacin, lomefloxacin, levofloxacin, moxifloxacin, sparfloxacin or enoxacin as an antibacterial substance. 3. The tool according to claim 1, characterized in that it contains as an auxiliary substance chlorhexidine bigluconate, lidocaine hydrochloride, sea buckthorn oil, rosehip oil or a mixture thereof. 4. The tool according to claim 3, characterized in that it contains chlorhexidine bigluconate in an amount of 0.001-0.01 wt.%. 5. The tool according to claim 3, characterized in that it contains lidocaine hydrochloride in an amount of 0.5-1.0 wt.%. 6. The tool according to claim 3, characterized in that it contains sea buckthorn oil or rosehip oil, or a mixture thereof in an amount of 5.0-7.0 wt.%.

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