RU2122865C1 - Method of treatment medicinal stuff hands, suppurative wounds, injection and operative fields and sterilization of medicinal tool - Google Patents

Abstract

FIELD: medicine, disinfection. SUBSTANCE: invention proposes the use of 0.5-2-% aqueous or 0.5-% aqueous-alcoholic solutions of polyhexamethyleneguanidinium phosphate of the formula:

Description

 The invention relates to medicine and can be used in surgery, obstetrics, cardioangiography, etc.

 The development of chemical antiseptic methods remains an urgent problem due to the constant change in the species composition and properties of pyogenic microbial flora, which in turn leads to a decrease in the effectiveness of antibiotic therapy, to the development of an unfavorable situation in many surgical hospitals in connection with nosocomial infections.

 Currently, for the treatment of the hands of medical personnel, purulent wounds, surgical fields, as well as for the sterilization of instrumentation, solutions of chlorhexidine bigluconate ("Plivacept"), a drug manufactured by Pliva (Croatia), are used [1].

 In Russia, the pre-sterilization treatment of instruments used in endoscopy and cardiography is carried out in accordance with the instructions of the Ministry of Health and the Ministry of the RSFSR N 16 of 03.09.1990, “Information on the disinfection and pre-sterilization cleaning of instruments” with imported 2% Sidex solution (2.5% glutaraldehyde in 6% hydrogen peroxide) or a solution manufactured by KIFA (Sweden) having the following composition: ethyl alcohol 96% - 750 ml, formalin 35% - 25 ml, distilled water - 225 ml, sodium bicarbonate - 1 g per 1 liter of solution .

 The disadvantage of Sidex solution is its instability due to the use of hydrogen peroxide, and a significant exposure period of sterilized products. The disadvantage of the disinfectant solution manufactured by KIFA is the high volatility of alcohol and formalin, which entails their significant consumption during intensive work, as well as the relatively long exposure period of sterilized products.

 The closest analogue of this invention used in the treatment of the hands of medical personnel, purulent wounds, injection and surgical fields is chlorhexidine bigluconate, which has a wide range of microbicidal and sporocidal activity. When processing the skin, its 0.5% alcohol solutions are used, while disinfecting instruments - 2% aqueous solutions. The disadvantage of this drug is its high cost, the resistance to it of some hospital strains of microbes, as well as its relatively high toxicity.

 The objective of the invention is to remedy these disadvantages. This is achieved by the fact that 0.5% alcohol solutions of polyhexamethylene gluanidine phosphate (fogucide) are used as an antiseptic when treating surgical fields, 0.5% aqueous solutions of fogucide are used to treat the hands of medical personnel and purulent wounds, and 1-2% when disinfecting instruments aqueous solutions of fogucide, for hygienic antiseptics - 2% solutions of fogucide and its composition with surfactants.

где n = 5-30,
получают из гидрохлорида полигексаметиленгуанидина, выпуск которого освоен отечественной промышленностью. Способ получения фосфата полигексаметиленглуанидиния описан в [2].Polyhexamethylene guanidine phosphate formula

where n = 5-30,
obtained from polyhexamethylene guanidine hydrochloride, the production of which has been mastered by domestic industry. A method for producing polyhexamethylene gluanidinium phosphate is described in [2].

 Table 1 presents summary data on the toxicity and hazard parameters of fogucide solutions in the skin route of entry into the body in comparison with the imported antiseptic chlorhexidine bigluconate.

 The table shows that fogucid, which has a high molecular weight relative to chlorhexidine, is a less toxic substance. When applying its solutions on the surface, a film is formed that retains antiseptic properties for a long time. Thus, in terms of efficiency, safety of use, stability and low cost, Fogucid is superior to the best foreign samples: chlorhexidine bigluconate, vantocil, cosmocyl [3].

 The invention is illustrated by examples.

 Example 1. The treatment of the hands of medical personnel with solutions of fogucide.

 The tests were carried out in accordance with the recommendations of the German Society of Hygienists and Microbiologists (1981) and their supplements (1984, 1991).

According to these recommendations, the antimicrobial activity of antiseptics, disinfectants is tested on standard test strains. In the experiments, a 16-20 hour culture of test strains suspended in a 0.5% neutral pH sodium chloride solution was used. The density of the culture should be set to 10 ⁸ -10 ¹⁰ KOE / ml. Preparations for prophylactic antiseptics should have a quick microbostatic or microbicidal effect when applied once or twice with a small interval. Therefore, the time of action of the drug on bacteria is set from 30 s to 5 minutes. A series of dilutions of the test drug is being prepared that have and do not have an antimicrobial effect on bacterial test strains. The experiment is controlled by the sensitivity of the test strains to phenol (1%, 0.5%, 0.25%, 0.125%, etc. dilutions in a 0.5% sodium chloride solution).

 With the admission of new drugs in medical practice put: a) high-quality suspension test; b) quantitative suspension test; c) a test close to the practice of using antiseptics.

 Determination of bacteriostatic and fungistatic activity of the antiseptic fogucid in a qualitative suspension test.

The test drug was diluted in concentrations: 2%, 1%, 0.5%, 0.025%, 0.05%, 0.25%. To the dilutions of the preparation, 20-hour cultures of test strains of five types were added: E. coli, Staphylococcus aureus mirabella protea, blue-purulent bacteria, white candida. The density of the culture corresponded to 10 ⁹ KOE / ml; the exposure time was 0.5, 1.3, and 5 min. After the expiration of the test strains were seeded on KCA medium, candida - on Saburo medium. The period of incubation of bacteria was 48 hours at a temperature of 37 ^o C, candida - 72 hours at 20-25 ^o C. The results were taken into account inhibition of microbial growth. The data obtained are presented in table 2.

 From table 2 it is seen that the solutions of fogucide are much more effective than solutions of phenol. Fogucid has a detrimental effect on gram-positive microflora in a concentration of 0.5-2%, gram-negative - 0.05-1%.

 For a hygienic antiseptic, a drug is considered suitable if it inhibits the growth of all test microbes in 0.5-1 minutes at an acceptable tolerance concentration. A drug intended for surgical hand antiseptics should inhibit the growth of all test strains during 3-5 minutes of exposure in an acceptable tolerance concentration.

 The data obtained indicate that 0.5-1% solutions of fogucide can be used for surgical treatment of hands, and a 2% solution for hygienic antiseptics.

 Determination of the activity of fogucide in a quantitative suspension test.

The test was carried out on test strains of E. coli and Staphylococcus aureus. The density of the culture was 1 • 10 ⁹ KOE / ml. Test concentrations were taken based on the results of a quality suspension test. Phenol is used as a control. A mixture of the preparation and culture was incubated for 0.5, 1, and 5 min. After the incubation period was seeded on KSA. The activity of the drug was evaluated by the degree of decrease in KOE / ml compared with the control. Preparations for hygienic antiseptics should reduce KOE / ml of E. coli and staphylococci at a concentration recommended for use for 0.5-1 min by at least 5 decimal logarithms. Preparations for surgical antiseptics should provide the same degree in 3-5 minutes. (tab.).

 According to this test, the preferred concentration of fogucide solutions for surgical antiseptics is 0.5-1%, for hygienic antiseptics - 2% solution.

 Determination of the activity of fogucide in tests close to practical application.

 In Europe, the second standard of effective surgical antiseptics is considered to be a decrease in the KOE of bacteria, which is achieved after double treatment of the hands with 60% isopropanol [2].

After washing with soap and water under running water, the volunteers' hands were lowered into a suspension of E. coli strain 1 • 10 ⁹ . At the second stage, the hands were dried in air for 3 minutes, at the third stage, they were washed off from the contaminated areas of the hands, placing them for 1 minute in saline solution, at the fourth stage, the contaminated areas of the hands were wiped with 3 ml of the antiseptic concentration selected according to the results of suspension tests for 1 minute for hygienic antiseptics and for 5 minutes, 5 ml of the drug for surgical antiseptics, at the fifth stage, rinsing was done from contaminated, processed and neutralized skin areas. A 60% isopropanol solution was used in the control.

 Evaluation of the effectiveness of the test drug is carried out by comparing the degree of decrease in the number of Escherichia coli (with artificial microbial contamination - 5 decimal logarithms). This test confirms the correctness of the selected concentrations.

 Next, we conducted a comparative assessment of the effectiveness of fogucide and chlorhexidine for the treatment of the hands of personnel involved in operations.

 The tests were carried out on volunteers (60 experiments) with an exposure of 1 min, 5 min, 1 h. Hands were thoroughly washed with running water and soap. Dried with a sterile cloth. Then 3 ml of the preparation was applied and rubbed for 1 min for a hygienic antiseptic. For surgical antiseptics, they rubbed it into the skin for 5 minutes, repeating the procedure twice. Crops for sterility were taken with the hands treated with the drug. They wore sterile gloves. An hour later, repeated seeding was done to determine the effectiveness of the antiseptic.

 In boxing conditions, the washings were inoculated on the medium in compliance with the rules of the septic tank, eliminating the possibility of secondary contamination. To do this, the air contamination in the box was checked (two Petre dishes with nutrient agar were put on a work table, kept open for 15 minutes and placed in a thermostat for 24 hours). The results are presented in table 6.

 The table shows that the use of 0.5-2% solutions of fogucide in the surgical and hygienic treatment of hands is more effective than chlorhexidine solutions, and the effect of the proposed drug as an antiseptic is longer.

 The study of the antibacterial activity of solutions of fogucide in the presence of surface-active compounds (surfactants).

 Polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) were used as surfactants in standard ratios with a final concentration of the active component from 0.5% to 0.001%. As a control, we used a traditional antiseptic - chlorhexidine in the same concentrations.

 For the experiment, a standard suspension of bacterial test cultures was prepared in the amount of 100,000 microbial cells, which was introduced into the test system containing the AGV nutrient medium and the studied drug in appropriate concentrations.

 As can be seen from the table, the use of surfactants does not affect the activity of the solutions of fogucide in relation to various types of bacteria, and in some cases even increases the activity of the test substance.

 Example 2. Treatment with a solution of fogucide injection and surgical fields.

In order to study the disinfecting properties of fogucid, we used its 0.5% solution in 70 ^o alcohol, as a control - 0.5% alcohol solution of chlorhexidine. Bacteriological monitoring of the effectiveness of the use of antiseptics was carried out in the bacteriological laboratory of the Irkutsk Regional purulent-septic center using the bacteriological analyzer "Sceptor" (Germany). 45 patients were examined in the process of their preparation for surgery. Of these, 21 - skin treatment was performed with chlohexidine (1 g.), 24 - with solutions of fogucide (2 g.). Diagnoses of patients: intestinal fistulas, purulent wounds of the anterior abdominal wall, phlegmon, subhepatic abscesses, empyema of the pleura, etc. Before applying the disinfectant solution, inoculation was taken from the untreated skin surface.

 In all patients of groups 1 and 2, the polymicrobial flora was obtained from the skin in the area of surgical intervention before surgery, most of which was able to initiate and support purulent-inflammatory processes.

 The operative field was treated with gauze napkins moistened with 0.5% alcohol disinfectant solution for 5 min, changing napkins twice during this time. After treatment, the surgical field was dried with a sterile dry cloth and the microflora culture was taken. After that, a sterile gauze napkin of four layers of gauze was glued onto the surgical field. Repeated crops were taken from the center of the surgical field after 30 and 60 minutes. Data on the effectiveness of the solutions used are presented in tables 8 and 9.

 As can be seen from the tables, before processing the skin from its surface, 70 cultures of microorganisms were obtained. After 5 and 30 minutes after treating the skin with a solution of fogucide, the field was sterile. When the skin is treated with a chlorhexidine solution, skin renification, probably by escalation of microorganisms from the spongy layers of the skin, occurs after 30 minutes. After 60 minutes, only 2 cultures were isolated in the 2nd group, and 11 in the 1st group.

 The data obtained allow us to conclude that a 0.5% alcohol solution of fogucide showed higher activity and was more effective against various bacteria compared to a 0.5% alcohol solution of chlorhexidine.

A bacteriological analysis of the effectiveness of a 0.5% solution of fogucide in 70 ^o alcohol in the disinfection of the skin in the field of injection and catheterization of blood vessels. A 0.5% alcohol solution of chlorhexidine was used as a control. 27 patients of the hemodialysis department were examined. Of these, 17 were treated with a solution of fogucide and 10 with a solution of chlorhexidine. The data are presented in table 10 and 11.

 The tables show that the effectiveness of the treatment of the injection field with both drugs did not differ significantly. However, in a general assessment of the results obtained, no bacteria such as E. coli, Ps were found in patients of this group. aeruginosal, St. aureus. In 45 patients with a purulent-septic center, 133 cultures of microorganisms (295%) were isolated in the initial skin cultures, and in 27 patients, the hemodialysis and angiography departments were half as much (148%). Consequently, with a higher bacterial contamination of the skin, including microorganisms that cause the most severe clinical forms of inflammation, fogucid was more effective than chlorhexidine. This is of particular importance in conditions of hospitalization and during operations in purulent patients.

 Example 3. The study of the effect of an aqueous solution of fogucide on the healing of purulent wounds.

 Experimental studies were carried out on non-inbred male Wistar rats weighing 200-240 g. The total number of experiments was 443. Of these, 10 were used to develop models of flat purulent wounds, 10 made up the control group, 0.05% were tested in 12 a solution of fogucide (experimental group N 1) and 12% - 0.1% solution of fogucide (experimental group N 2).

 After depilation of a 3x3 cm skin area, a rounded flat wound (diameter 2.3 cm) was created on the back of the animal to the right of the spine. The bottom of the wound was its own fascia. A titanium ring with an outer diameter of 2 cm and a height of 1.5 mm was fixed around the wound with four skin sutures to prevent skin contraction. 0.5 ml of 5% suspension of the contents of the colon (CTK) of animals was introduced into the wound. The microbiological landscape of STK is presented in table 12.

 The wound surface was covered with a flap of a cuprofan (dialysis) membrane preventing drying of the wound and the formation of a scab. It was found that the ring and membrane "work" for 6-8 days. In all experiments performed, except for the period of modeling, it was possible to achieve the formation of a typical purulent inflammation by the end of 2 days with its inherent signs: the presence of purulent exudate with an unpleasant odor, necrotic tissue, hypermia and infiltration around the wound.

 Wound lavage was carried out by introducing 3-4 ml of the test solutions with a syringe or catheter under the edge of the membrane onto the wound surface after its initial surgical treatment, which included removal of the scab and excision of visible necrotic tissue.

 To assess the course of wound healing, methods were used, the results of which are shown in table 13.

 The wound area was measured by weighing a paper template on a torsion balance (table 14).

The calculation of the regenerative-degenerative index was carried out according to the formula:
RDI = SAL + SAN / DFL,
Where
SAL - segmented white blood cells;
PYAL - stab leukocytes;
DFL - degenerative forms of white blood cells.

 With an index value> 1, we can talk about the end of the cleansing phase and the entry of the wound process into the regeneration phase.

 The determination of the amount of KOE per 1 g of biopsy specimen of the wound margin was carried out according to the Jould method in the modification of Ryatinsky-Rodoman. The data obtained are presented in table 15.

 Changing the pH of the wound surface was carried out by contact using a pH meter AGMI-01. As a result of significant differences between the studied groups in the dynamics of pH readings were not detected. To measure rectal temperature, Yellow Springs linear contact sensors (USA) were used. The data obtained are presented in table 16.

 The data presented in tables 13-16 indicate a statistically significant therapeutic effect when treating wounds with a 0.1% solution of fogucide, which is expressed in a more rapid normalization of rectal temperature, at an earlier onset of epithelialization, a decrease in the rate of degenerative changes in the cytogram, and a significant decrease in bacterial tissue seeded by 4 days. This indicates a pronounced antiseptic effect of fogucide and, at the same time, the absence of a local and resorptive toxic effect.

 Example 4. The processing of endoscopes and accessories with aqueous solutions of fogucide.

As objects used:
rubber anesthetic masks (10 pcs.); esophageal plastic bougie (10 pcs.); fiber optic gastroduodenoscopes "Olimpus" (10 pcs.); metal esophago- and bronchoscopes "Storz" (10 pcs.).

 After presterilizing cleaning of reusable instruments, it is treated with 0.5-2% aqueous solutions of fogucide. Using a gauze cloth soaked in these solutions, they wiped the outer surface of these objects. Unavailable to mechanical rubbing surfaces (instrument channels) were also washed with these solutions. In both cases, the time of constant contact of the sterilized surface with the disinfectant was from 1 to 5 minutes.

 When conducting bacteriological studies, it was found that the complete sterility of the instrumentation is achieved using 0.5% solutions for 5 min of treatment, and at 1% solution, by the end of the 3rd min of treatment.

In a special series of studies, endoscopes and products were infected (after their pre-sterilization treatment) with E-coli and St. test strains. aureus (10 ⁸ KOE / ml) using a cotton swab on the outer and inner surfaces of instruments and tools. Then, the contaminated objects were treated with aqueous solutions of fogucide according to the method described above. Material for bacteriological research was taken after 1, 3, 5, 10, 15, and 40 min after treatment with a 1% solution of fogucide. As a result, it was established that after 3, 5, etc. min, not a single case of the growth of microorganisms was noted. Thus, the sterilization time of endoscopic and auxiliary equipment is significantly reduced, the number of endoscopic examinations with a single device increases. In addition, the sterilization technique is greatly simplified, eliminating the repeated washing of the channels of flexible endoscopes and the use of special sterile chambers.

 Example 5. Sterilization of instruments used in cardioangiography with aqueous solutions of fogucide.

 For sterilization of products for angiography, a 1-2% solution of fogucide was used.

 Objects of study: metal products (catheter guides, transition valves, Seldinger needles, Gianturno spirals - 40 ed.); From polymeric materials (catheters of various devices, plastic cannulas, transition cranes (23 ed.).

For a rigorous assessment of the sterilizing capabilities of 1-2% solutions of fogucide, test subjects were infected with test strains of E. coli and St.aureus at concentrations of 10 ⁸ KOE / ml. After this product was treated with 1% (1st group of experiments) or 2% (2nd group of experiments) with aqueous solutions of fogucide. Material for bacteriological research was taken after 1, 3, 5, 10, 15, 40 minutes.

 When using a 1% solution of fogucid, the objects were free from E. coli for 10 minutes, and from St.aureus for 5 minutes of sterilization, whereas after applying a 2% solution of growth of microorganisms, no metal or and plastic products.

 Thus, the sterilization of products and instruments used in the process of angiocardiodiagnostic and therapeutic procedures using a 2% solution of fogucide is an effective and fast method. This is especially important if emergency sterilization or re-sterilization is necessary in case of accidental infection of products during the procedure.

 The proposed method expands the arsenal of methods for preoperative processing of products for angiocardiography, which is very important in hospital settings.

Literature
1. Krasilnikov A. P. Handbook of antiseptics. Minsk: Higher School, 1995.

 2. Lull I.Zh., Lidak M.Yu., Paegle T.A., Zideman A.A., Kravchenko N.N., Shlev A.P., Kagan G.I., Gembitsky P.A., Simkhovich B.Z. Copyright certificate N 944290., 1981., 03.23.1986., Bull. N 11.

 3. US patents N 2830006, N 4587266; 1986, Great Britain N 702268, 1969, Germany N 2437844, 1982

Claims (1)

A method of treating the hands of medical personnel, purulent wounds, injection and surgical fields and sterilizing medical instruments, which consists in applying an antiseptic solution, characterized in that 0.5 to 2% aqueous solutions or 0.5% are used as an antiseptic solution solutions of a mixture consisting of 70% ethyl alcohol and 30% water, and polyhexamethylene guanidinium phosphate of the formula

where n = 5 - 30.

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