RU2080864C1 - Agent for suppurative wound treatment - Google Patents

Abstract

FIELD: medicine, surgery. SUBSTANCE: agent has components at the following ratio, wt. -%: crystalline iodine, 0.5-0.7; metronidazole, 0.5-0.7; dimethylsulfoxide 30-40; and glycerol, the balance. Preparation shows activity against aerobic-anaerobic microorganism associations and does not cause by-side effects. EFFECT: accelerated reparative processes, decreased time of recovery. 10 tbl

Description

 The invention relates to medicine, namely to medicines and can be used in surgery for local treatment of purulent wounds.

 In the treatment of surgical infection, various iodine preparations are widely used. In recent years, they began to use iodine compounds with carrier solvents, which are used as high molecular weight active substances, polyvinylpyrrolidones, etc. (Mokhnach I.V. Iodine, high polymers and biological capabilities of the body. L. 1989, 78 pp. Kurbangaleev S.M. infections in surgery. M. 1985, 272 pp. Kuzin M.I. Kostyuchenok B.M. Kolper I.I. General principles for the treatment of purulent wounds // Vestnik of the Academy of Medical Sciences of the USSR, 1983, No. 8, pp. 45-49).

 Known tool for the treatment of purulent wounds from the group of iodophors iodinol obtained by attaching potassium iodide to polyvinyl alcohol (Mokhnach I.V. Iodine high polymers and biological capabilities of the body. L, 1979.-78 pp.). The drug is effective against a number of pathogenic microorganisms, especially against streptococci, staphylococci, has an antiviral and fungicidal effect. Iodinol is low toxic. It is used as an antiseptic for the treatment of surgical infections, as well as a disinfectant in obstetric practice for the treatment of staff hands.

 The main disadvantage of this drug is its low antimicrobial activity against gram-negative flora (Proteus, Pseudomonas aeruginosa, Escherichia coli) (Dachenko B.M. Chefranov A.V. Yuranov N.P. Complex means based on iodinol in the prevention and treatment of wound infections / / Clinical Surgery. 1987. N 1. S. 55-57).

 Known antiseptic iodopyron domestic iodophore, which is a mixture of a complex of polyvinylpyrrolidone potassium iodide with 1% content of active iodine. The drug has a high bactericidal activity against various microorganisms. It is used as an antiseptic for disinfecting the hands of surgeons, treating the surgical field (Limanov V.E. Suklasen A.M. Svitov I.R. Use of domestic iodor preparations based on pyrrolidone in the treatment of purulent wounds. Wounds and wound infection: Abstracts of the II All-Union Conference. October 28-29, 1986. S. 140-141).

 The disadvantage when using iodopiron is that aqueous solutions of the drug must be prepared immediately before use, because in diluted form, the drug is stored very little time. In addition, iodopyron does not have a dehydrating effect and it has poor penetrating ability, which significantly limits the therapeutic effect of the drug (Sologub V.N. The use of iodopyrone in the treatment of burn infection // Surgery. 1985. N 11. P. 92-98).

 Thus, the evaluation of analogues showed that, despite the high antimicrobial activity, they can be used very limitedly due to the high photosensitivity of the drugs, their instability, with painful, irritating and allergic effects on living tissues.

 As a prototype, an iodine-containing drug drug mixture based on a stabilized iodine cation was selected. the preparation consists (per 100.0 ml) of 500.0 mg of crystalline iodine dissolved in 40.0 ml of 100% dimethylpharmamide and liquid paraffin. The active active principle of this drug is iodine cations. Dimethylpharmamide acts as a solvent that promotes the penetration of iodine deep into the tissues. Vaseline oil was used as a stabilizer and inert diluent.

 The stabilized iodine cation is 0.5% antibacterial for the local treatment of various forms of purulent and burn infection (permission of the Pharmaceutical Committee of the USSR N 211-682 / 470). The drug has a pronounced bacteriostatic and bactericidal effect against clinical strains of Staphylococcus aureus golden and epidermal, Proteus, Pseudomonas aeruginosa, Escherichia coli, Salmonella, Shigella, Anthracoidis (Cherepanova T.A. New iodine-containing drug // Search for new drugs and their use in the clinic. Chita , 1990, part II, pp. 332-333).

 The main disadvantage of this drug mixture is that when treating a purulent infection, the bactericidal effect was only taken into account with respect to the aerobic component of microflora, and the presence of an anaerobic component, which is present in association with aerobes in 40-60% of cases, was completely ignored.

To reduce the time of cleansing wounds from purulent-necrotic masses and accelerate reparative processes by expanding the spectrum of the antimicrobial action of the drug and eliminating tissue ischemia in the pathological focus, it is proposed to use the drug "Iodmetroxide", consisting of crystalline iodine, metronidazole, dimethyl sulfoxide (DMSO) and glycerin the following ratios per 100.0 ml of solution:
crystalline iodine 300.0-800.0 mg
metronidazole 250.0-500.0 mg
dimethyl sulfoxide 30.0-40.0 ml
glycerin up to 100.0 ml
The main bactericidal ingredients in the proposed drug mixture are crystalline iodine and metronidazole. DMSO is used as a solvent that promotes the penetration of the ingredients of the mixture into the tissues. Glycerin is a stabilizer and diluent for the drug mixture.

 Based on the foregoing, a comprehensive drug mixture is proposed for the treatment of purulent wounds of various etiologies, the hallmarks of which are the combined antibacterial effect against aerobic-anaerobic associations of microorganisms without a general and local toxic effect on organs and tissues, a deep mechanism of action.

 In contrast to the known iodine-containing preparations, the claimed medicinal composition "Iodmetroxide" has more pronounced antibacterial properties against the main causative agents of wound infection (table. 1).

 Iodomethroxide contributes to a more rapid cleansing of wounds from purulent necrotic masses, which was established during experimental and clinical studies (Tables 2, 3, 4).

In addition, it has been reliably established that the proposed drug mixture has a pronounced antioxidant effect on tissues in the area of the pathological focus in conditions of tissue ischemia,
which significantly improves the reparative processes of the wound (tab. 5, 6, 7).

 To determine the shelf life of the antimicrobial activity of iodomethroxide, the drug was examined for bactericidal activity every 3 months for 1.5 years of storage, and the appearance of the drug was studied, i.e. its color and transparency in comparison with freshly prepared.

The drug was stored at a temperature of +4 ^o C and at room temperature.

 The bactericidal activity of the drug was determined by comparing the minimum bacterial concentration (MBcc) every 3 months. The microbial load was 100,000 microbial bodies per 1 ml of medium.

 It was found that the test solution did not change its appearance over 1.5 years of storage, color and transparency did not differ from freshly prepared. MBcK of the main strains of microorganisms did not change (table. 8).

 The locally irritating properties of iodomethroxide were studied by its action on the skin in 10 white rats according to the method of R.V. Krylova (1985) for 3 months.

 A histological study of skin pieces at the site of application of the drug and the internal organs of animals was carried out according to the method of G.A. Merkulova (1968).

 Morphological changes in the skin and internal organs of experimental animals were not detected.

 In the clinical use of iodomethroxide in established concentrations, no local and general side effects were detected.

 The quantitative composition of the main bactericidal ingredients was determined experimentally.

 It was found that a concentration of iodine and metronidazole of less than 500 mg per 100 ml does not have pronounced antibacterial properties, and a higher concentration of 800 mg per 100 ml has a locally irritating effect with a slight increase in the antibacterial effect (Table 9).

 Thus, iodomethroxide is technologically reproducible in the boundary and averaged values of the ingredients.

 It was established that the total effect of the bactericidal effect of the composition of the drug's medicinal substances upon their synergism exceeds the sum of the effects of the components separately.

 The drug mixture is prepared by mixing from the following ingredients per 100 ml of liquid (wt.): Crystalline iodine 0.5-0.7; metronidazole 0.5-0.7; DMSO 30.0-40.0; glycerin rest.

 30.0 ml of 100% DMSO are added to the first flask and 0.5 g of crystalline iodine is dissolved in it. 10.0 ml of liquid metronidazole (0.5 g) is poured into the second flask and dissolved in 10.0 ml of 100% DMSO. Then, the contents of the first are added to the contents of the second flask, the total volume is adjusted to 100.0 ml by adding glycerol. The resulting liquid is thoroughly mixed and packaged in 100.0 ml glass drums for medical preparations.

The finished product is an orange-yellow liquid, viscous consistency, stored in bottles at room temperature or in a refrigerator at a temperature of +4 ^o C.

 As examples illustrating the use of iodomethroxide in patients with purulent wounds, we present the following observations.

Example 1. Patient M., 26 years old, was admitted to the hospital with a diagnosis of post-injection abscess of the left gluteal region. Upon admission: satisfactory condition, body temperature 38.2 ^o C. In the left gluteal region there is an infiltrate measuring 12x15 cm, sharply painful on palpation, fluctuation is determined in the center. The skin is hyperemic, local hyperthermia is noted.

An abscess was opened, about 100.0 ml of pus was obtained. During bacteriological examination, Escherichia coli was isolated in association with gram-positive cocci (peptococcus), microorganisms resistant to tetracycline, carbenicillin, lindomycin, gentamicin, lincomycin, chloramphenicol, erythromycin, dioxidine, microcide. The degree of microbial contamination per 1 g of tissue is 10 ⁷ , in the cytograms abundant microflora (+++), completely destructively altered neutrophilic leukocytes. The content of the partial pressure in the wound is 4.6 mm RT. Art. the level of malondialdehyde (MDA) in the blood serum is 2.22 μmol / ml.

 At a local examination, there is a purulent wound measuring 7x3x5 cm with edematous, infiltrated edges, copious purulent discharge from the wound, the walls and bottom of the wound are covered with fibrinous-necrotic masses.

 Iodomethroxide treatment started. On the 3rd day after the operation, the wound cleansed of purulent-necrotic masses, the discharge was significantly reduced. By 4 days, the walls and bottom of the wound are filled with islands of granulation tissue.

Lack of growth during bacteriological examination occurred on the 3rd day, microbial contamination at the same time amounted to 10 ³ . By 5 days, the partial pressure of oxygen in the wound is 17.6 mm Hg. the MDA level is 1.79 μmol / ml. In the cytograms, the pathogenic flora is absent, 34-36% neutrophilic leukocytes without signs of degeneration, macrophages 3-5% of polyblasts 35%, their active transformation into profibroblasts is noted. On the 5th day secondary sutures were applied, healing without complications. The length of stay in the hospital is 8 bed days.

Example 2. Patient Ch. 33 years old, medical history 22033, operated on for acute gangrenous-perforated appendicitis. The postoperative period was complicated by suppuration of the wound. The next 12 days, local treatment of the wound was carried out with a hypertonic solution of sodium chloride, Baliz-2, dioxidine, but to no avail. Sowing wound contents gave rise to Pseudomonas aeruginosa in association with a protein resistant to monomycin, kanamycin, dalacin C, vibramycin, and chloramphenicol. Wound contamination with microorganisms per 1 g of tissue - 10 ⁷ , 10 ⁸ , pO _{2 of the} wound is 7 mm Hg the blood MDA content is 2.34 μmol / ml.

The treatment of the wound with dressings with iodomethroxide has begun. By 3 days after treatment, the patient's condition improved, and body temperature returned to normal. At a local examination, the wound decreased in size, detachable body. At a local examination, the wound decreased in size, there is no detachable, the walls and bottom of the wound are covered with islands of delicate granulation tissue, in some areas there is fibrin plaque. On day 4, bacteriological control of the wound contents did not give growth, microbial contamination does not exceed the critical level - 10 ² -10 ³ . Microbial bodies are not detected in cytograms, neutrophilic leukocytes in a small amount, the number of histiocytic elements noticeably increases (17-20% in the field of view). On the 6th day, a wound measuring 4.5x0.5 cm was made with fine-grained granulation tissue, marked marginal epithelization was noted.

 Example 3. Patient K., 34 years old, operated on for post-traumatic chronic osteomyelitis of the left tibia in the middle third in the acute stage.

 During the operation, wound material was taken in the form of a fragment of bone and muscle tissue for bacteriological examination. Escherichia coli is sown in association with gram-negative cocci, which are highly resistant to lincomycin, kanamycin, gentamicin, dioxidine, ristomycin, tetracycline, erythromycin.

During the operation and on the 1st day, microbial contamination per 1 g of tissue was 10 ⁷ -10 ⁸ , pO ₂ in the pathological focus area of 5.2 mm Hg the level of MDV is 2.12 μmol / ml, ADP is 64.0 mmol / l, MAF is 37.7 mmol / l.

 In the postoperative period, local drug treatment was carried out with iodomethroxide using inflow and outflow drainage.

By 3 days of growth in bacteriological crops was not detected, microbial seeding below the critical level and is 10 ² -10 ³ , the level of pO ₂ 17 mm RT. Art. The MDV content is 1.78 μmol / ml, ATP 625.7 mmol / L, MAF 28.5 mmol / L.

 On day 8, the sutures were removed, healing by first intention. With further observation in the patient for 1.5 years, a relapse of the disease was not observed. Comparative data are given in table. ten.

Claims (1)

 A means for treating purulent wounds containing crystalline iodine, a dipolar solvent and a stabilizer, characterized in that it further contains metronidazole, dimethyl sulfoxide as a solvent, and glycerol in the ratios, wt. Crystalline iodine 0.5 0.7
Metronidazole 0.5 0.7
Dimethyl sulfoxide 30.0 40.0
Glycerin Else,

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