RU2351365C2 - Antiseptic composition "chlordix" - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, particularly medicinal substances, which have antiseptic activity, can be used for progressing instrument, hands, wounds, cavities. Composition contains 0.05% - 0.5% water solution of chlorine hexidine or its salts and 0.1%-5% water solution of dioxydine with definite component ratios.

EFFECT: invention ensures broad spectrum of activity, including activity with respect to acid-resistant bacterial forms.

1 tbl, 1 ex

Description

The composition relates to medicine, in particular to medicinal substances with antiseptic activity, and can be used to treat instruments, hands, wounds, cavities.

Chlorhexidine [-1,6-Di- (para-chlorophenyl-guanido) -hexane] (Chlorhexidinum) is known.

Available in the form of a bigluconate (Chlorhexidini bigluconas). Chlorhexidine is one of the most active local antiseptic agents. Chemically, it is a dichloro-containing derivative of biguanide. Chlorhexidine has a fast and strong bactericidal effect on gram-positive and gram-negative bacteria. Not valid for viruses and spores. The drug is stable and after processing the skin (hands, surgical field, etc.) it remains on it in a certain amount, which continues to give a bactericidal effect. The drug remains active in the presence of blood, pus, although somewhat reduced. They are used to treat the surgical field and hands of the surgeon, sterilize surgical instruments, as well as in purulent-septic processes (washing surgical wounds, bladder, etc.).

Effective against pathogens of sexually transmitted infections - gardnerelez, genital herpes; gram-positive and gram-negative bacteria - Treponema spp., Neisseria gonorrhoeae, Trichomonas spp., Chlamidia spp., Ureaplasma spp.

Disadvantages of the drug: does not affect acid-resistant forms of bacteria, microbial spores, fungi (http://www.webapteka.ru/drugbase/name14640.html).

Known Dioxidine [2,3-bis- (hydroxymethyl) quinoxaline-N, N'-dioxide] (Dioxydlnum), international name: Hydroxymethylquinoxylindioxide, group accessory: antimicrobial agent, quinoxaline, a synthetic drug that has a bactericidal effect and has a broad antimicrobial spectrum. Due to its high toxicity it is intended mainly for topical use.

It is active against Proteus vulgaris, Pseudomonas aeruginosa, Friedlander bacillus, Escherichia coli, Shigella dysenteria, Shigella flexneri, Shigella boydii, Shigella sonnei, Salmonella spp., Staphylococcus spp., Streptococcus spp., Pathogenic perfen. It acts on strains of bacteria resistant to other antibacterial drugs, including antibiotics. It has no local irritating effect. Perhaps the development of drug resistance of bacteria. The treatment of burns and purulent-necrotic wounds promotes faster cleaning of the wound surface, stimulates reparative regeneration and marginal epithelization, and favorably affects the course of the wound process. (http://www.webapteka.ru/drugbase/name2135_desc806.htrm)

The disadvantages of the drug are:

narrow therapeutic breadth (Practical Guide to Anti-Infectious Chemotherapy, edited by: L. S. Strachunsky, Yu. B. Belousov, S. N. Kozlova http://www.antibiotic.ru/ab/076-77.shtml);

lack of criteria for assessing the sensitivity of microflora (Modern antimicrobial chemotherapy L. S. Strachunsky, S. N. Kozlov. A guide for doctors: http://antibiotic.ru/books/mach/mac0113.shtm1#p1307).

It is known to use chlorhexidine and dioxidine in antiseptic compositions as the drugs of choice. For example, in the source: US Pat. No. 1799553 (SU), publ. 1993.03.07 “Method for the treatment of jaw cysts” indicated the use of a 1% solution of dioxidine or 0.04% solution of chlorhexidine bigluconate for treating bone cavities.

In the source: US Pat. No. 2275179 (RU), publ. 2006.04.27 “Dressing for closing and treating burns” it was also proposed to use one of the drugs: “... Antiseptic drugs of the treatment layer are: chlorhexidine, ... or dioxidine”.

In the source: US Pat. No. 99123233 (RU), publ. 2001.08.10 “A method for treating purulent wounds with a saline solution based on a high molecular weight fraction (Navy) of dextran waste” uses “... an antiseptic - chlorhexidine bigluconate per 0.2 g per 1 liter of solution or an antiseptic dioxidine per 5 g per 1 liter of solution” . In the sources available to us, information on the combined use of dioxidine and chlorhexidine was not found.

Chlorhexidine gluconate and ethyl alcohol (WO 1995/012395, 05/11/1995 TOPICAL ANTIMICROBIAL CLEANSER CONTAINING CHLORHEXIDINE GLUCONATE AND ALCOHOL), 05.11.1993.711.199.37 ) However, ethyl alcohol has a local irritant effect, which reduces the therapeutic value of the use of the claimed composition.

Known antiseptic composition (WO 1997/032479) dated 09/12/1997 "ANTISEPTIC COMPOSITIONS CONTAINING CHLOROBUTANOL AND CHLORHEXIDINE" (96/02685 03/04/1996 FR), containing a combination of chlorhexidine with another antiseptic chlorobutanol in the following proportions: chlorine chloride 0,000,000 0.01% m / V, chlorobutanol - at a concentration of about 0.2% m / V.

The purpose of the invention is the creation of an antiseptic composition with a wide spectrum of bactericidal activity, high safety, economic availability.

The result is achieved through the use of a combination of well-known, generally available and inexpensive antiseptics of chlorhexidine and dioxidine.

The composition showed higher bactericidal activity against strains of various microorganisms in comparison with the separate use of chlorhexidine and dioxidine in the same concentrations, which can be illustrated by the table. Bacterial agents commonly found in surgical practice, such as Enterobacter spp. and Citobacter spp., Klebsiella, E. Coli, Pseudomonas aeruginosa, Staphylococcus aureus, were plated on nutrient media by conventional methods (see "Fundamentals of Microbiology, Virology and Immunology / Textbook for medical students, Mastery, 2001. ISBN: 5- 294-00053-9, 224 pp. ”Or“ Microbiology, immunology, virology ”Borisov LB, Publisher: M .: Medical Information Agency LLC, 2005. - 736). In the bacteriological laboratory of the State Health Institution “Voronezh Regional Clinical Hospital No. 1,” several series of experiments were carried out in which control culture was used without adding antiseptic agents to the culture media and experimental crops were added with dioxidine and chlorhexidine in the following concentrations and proportions (see table) .

Table The activity of bacterial microflora under the action of an antiseptic composition Concentration of ingredients Share ratios 1: 1 1: 5 1: 9 5: 1 9: 1 1% solution of dioxidine + 0.05% solution of chlorhexidine - - - - - 0.5% solution of dioxidine + 0.05% solution of chlorhexidine - - Staphyl. aureus - - 0.1% solution of dioxidine + 0.05% solution of chlorhexidine - - - - Staphyl. aureus 0.01% solution of dioxidine + 0.05% solution of chlorhexidine E.Coli - - - - 1% solution of dioxidine + 0.025% solution of chlorhexidine - - - - - 1% solution of dioxidine + 0.005% solution of chlorhexidine - - - - - 1% solution of dioxidine + 0.0005% solution of chlorhexidine - St. aur .; E. coli; Pseud.aer. - - -

These tables demonstrate the high bactericidal activity of the claimed composition, the growth of microflora is observed only in samples with dilutions of preparations lower than recommended or when the content of one of the ingredients of the composition is reduced to less than 10%.

In addition to potentiating bactericidal activity, we found an effect that is not characteristic of the ingredients taken separately. When using an aqueous solution of chlorhexidine in the concentration range of 0.01-0.5% and an aqueous solution of dioxidine in the concentration range of 0.1-5%, the ratio of the mass fractions of each of the ingredients in the range from 10 to 90 wt.% Marked activity when acting on acid resistant forms of bacteria such as Helicobacter pylor and Micobacterium tuberculosis.

A series of experiments was carried out, confirming the appearance of a new property of the proposed composition.

Micobacterium tuberculosis, which was grown in vitro. For cultivation, New and Levenshtein-Jensen media were used, prepared simultaneously in accordance with the methodological recommendations of the Ministry of Health of the RSFSR of 1972. "Preparation and use of a nutrient medium for growing mycobacterium tuberculosis." Prior to the research, standard monitoring of the quality of nutrient media was carried out in the bacteriological laboratory of the Federal Penitentiary Service of Russia in the Voronezh Region “Regional TB Hospital No. 1”. The result was evaluated 90 days after sowing.

In the experimental series in the presence of an antiseptic composition, colony growth was reduced by at least two times if dioxidine and chlorhexidine were taken at concentrations of 0.01-0.9% and 0.01-0.5%, respectively. At concentrations of dioxidine of at least 0.9% and chlorhexidine of at least 0.05% in ratios of 10 to 90 wt.%, The crops are sterile.

Similar results were obtained for Helicobacter pylor (HBp), which was grown on blood agar at 37 ° C. In control crops on the 5-7th day of cultivation in the control sample, growth of small transparent shiny colonies was observed, in the experimental series a pronounced bactericidal effect was observed.

The activity of the claimed composition against Helicobacter pylor is confirmed by the following clinical examples.

Patient V., 51 years old, was diagnosed with gastric ulcer with multiple erosive mucosal lesions and a pronounced pain symptom, confirmed by fibrogastroscopic and histological examination.

The oral administration of the claimed antiseptic composition prepared using aqueous solutions of chlorhexidine biguanide and dioxidine in ratios of wt% 52 and 48, respectively, was taken three tablespoons 3-4 times a day 30 minutes before meals for three days.

In the control FGS study a week after the start of treatment, cicatricial changes in the gastric mucosa, HBP was not sown. The pain syndrome is stopped.

A spectrometric study carried out at the chemistry department of Voronezh State University by thin-layer chromatography on Merck plates, a UV lamp developer and UV spectroscopy using a Shimatsu UV spectrometer, Japan, found that the ingredients of the solution of our composition do not enter into the chemical interaction among themselves. That is, the proposed composition is not a new chemical compound and is a mixture of two substances.

Thus, the claimed antiseptic composition has a higher bactericidal activity in comparison with individual ingredients, has a new property - the ability to act on acid-resistant microorganisms, low cost in comparison with antimicrobial agents similar in activity and ease of preparation.

Claims (1)

An antiseptic composition containing chlorhexidine or its salts for the treatment of hands, wounds, cavities, instruments, characterized in that it further comprises an aqueous solution of dioxidine in the following components, wt.%:
0.05-0.5% aqueous solution of chlorhexidine or its salts 10-90 0.1-5% aqueous dioxidine solution 90-10