CS240076B1 - Synergic microbicidal agent - Google Patents

Abstract

Synergistic microbicidal preparation for wide use in medicine, especially in veterinary medicine. The preparation is broad-spectrum, strongly colored and non-irritating when used topically. It consists of 0.1 to 1 wt. % of carbethopendecinium bromide or chloride, 0.1 to 2 % of methyl violet and 2 to 20 % of benzyl alcohol in addition to the usual excipients used in the formulations of aerodispersible preparations. The preferred ratio of active ingredients in the above order is 0.5 : 0.5 : 10 by weight.

Description

The invention relates to a combined biocidal preparation for wide use in medicine. Especially in veterinary medicine for prophylaxis of infection in newborn animals in local application to the umbilical stump. Deinfection of superficial wounds, especially in sensitive areas, disinfection of body surfaces before surgical procedures.

The products used so far contain substances that do not have a sufficiently broad spectrum of action, they have been used for a relatively long time and the resistance of some microorganisms to them is obvious. If they are colored, they are colored with auxiliary substances - dyes.

The essence of this invention is that, in addition to the usual excipients used in aerosol formulations, it consists of a mixture of three active substances - namely carbendazim bromide, methyl violet and benzyl alcohol, which are compatible and mutually potentiated, so that a higher antimicrobial effect is achieved, the preparation acts on a wider spectrum of microorganisms. At the same time, the coloring power sufficient for the given purposes is guaranteed without the need to add a dye and the preparation shows a lower irritation potential than the original one, which did not contain benzyl alcohol.

All three active ingredients of the subject invention are known, widely used substances in various applications.

Carbethopendecinium bromide is one of the most widely used disinfectants in our country. International analogues of this substance, e.g. Cetrimide and other quaternary ammonium bases have been used for the same/ · /similar purposes for many years. In CsL 3, carbethopendecinium bromide is listed as Carbaethopendecinium bromatui. The vast majority of pharmacopoeias list some quaternary ammonium base.

Methyl violet is a widely used substance due to its safety in use and the possibility of easy control of application. The substance is indicated as an antiseptic, antifungal, disinfectant and anthelmintic.

It is listed as Methylroaanilinium chloratum in CaL 3. It is also listed in the British Pharmacopoeia /BP 1973/, the Japanese Pharmacopoeia /PhJap 197V,

GDR /2.AB-DDR/, Nordic /PhNord 63/, Swiss /PhHelv VI/,

- 2,240,078 in the Austrian /OeAB IX/ and in the US Pharmacopoeia /USP XX/.

Benzyl alcohol is an adjuvant in a wide range of parenteral preparations, where it is used as a solvent for active substances and as a preservative. It is listed in a wide range of pharmacopoeias: CsL 3, PhHelv VI, PhNord 63, OeAB IX, BP 1973, PhJap 1971,

Pharni. franc. 1972 and NF XIV. It is an antiseptic, disinfectant and slightly anesthetic substance.

Alcohols, glycols, ketones, macrogols /ethyl alcohol, propanol, isopropanol, ethylene glycol, propanediol, methyl ethyl ketone, acetone and macrogols with an average molecular weight of 200-1000/ can be used as solvents for this purpose.

To adjust the adhesive properties of the product, a

acrylate copolymer /Akutol/, polyvinyl alcohol, polyvinylpyrrolidone and a whole range of cellulose derivatives suitable for application in an anhydrous environment.

The negative impact on the skin in terms of degreasing effect is limited by adding so-called super-oil additives - isopropyl palmitate, isopropyl myristate, hexyl lauric acid ester, di-n-butyl adipate, decyl oleic acid ester, 2-octyldodecanol, a mixture of caprylic and capric acid triglycerides, isopropyl stearate, ethoxylated lanolin, ethoxylated cholesterol.

The biocidal mixture is forced out of the container by the content of propellant gases (a mixture of trichloromonofluoromethane and dichlorodifluoromethane) in an appropriate ratio and sufficient quantity. The gas overpressure in the package is a maximum of 0.4 MPa at 20°C.

The subject matter of the invention is further illustrated by way of example without being exclusively limited thereto.

Example No. 1

Carbethopendecinium bromide

Methylviolet

Benzyl alcohol

Palmitic acid isopropyl ester p

Acrylate copolymer /Akutol / Isopropyl alcohol Trichloromonofluoromethane Dichlorodifluorothane

0.50% by weight 0.30% by weight

10.00% by weight 4.20% by weight

20.00% by weight 14.73% by weight 30.00% by weight 20.00% by weight

- 3 Example No. 1 - Preparation method

240,078

Methylviolel, carbethopendecinium bromide, palmitic acid isopropyl ester and acrylate copolymer are dissolved in isopropanol. The solution is mixed at room temperature and then filtered through a cloth into a container. On an automatic line, the concentrate is filled into containers that are closed with a valve. The propellant gases are filled through the valve as the last operation. The process takes place in a laminar flow cabin.

The synergistic effect of the active ingredients was confirmed in the testing of the preparations, always omitting some of the ingredients in the formula.

SCS variant 01 /carbethopendecinium bromide omitted/

SOS variant 02 /omitted methyl violet/

SCS variant 03 /carbethopendecinium bromide and benzyl alcohol omitted/

SCS variant 04 /carbethopendecinium bromide and methylvioleum omitted/

SCS variant 05 / omitted carbethopendecinium bromide, methyl violet*t and benzyl alcohol/

SCS variant 06 /complete composition/

The results are shown in Table 1.

SCS - working designation of samples

Tested microorganisms

Staphylococcus aureus 771

Staphylococcus epidermidis /kk/ Streptococcus pyogenes sk. B /kk/' Streptococcus faecalis /'kk/

Escherichia coli Ec 185/59 SZK CEM-IHE Proteus mirabilis 7/44

Pseudomonas aeruginosa King/R+/84 Bacillus cereus /kk/

Candida albicans Ca-1 Saccharomyces cerevisiae Sce/83 Corynebacterium pyogenes /kk/ Salmonella typhimurium /kk/ kk - clinical strain

Test soils

Mueller Hinton Broth Difco for gram-negative rods and staphylococci Mueller Hinton Broth Di#co with 10% rabbit serum for streptococci and • corynebacteria

Sabouraud Dextroae Broth Oxoid for Yeast ^{240 078}

Workflow

The contents of the Erlenmeyer flasks were thoroughly shaken and then various dilutions of the individual variants of the tested batch were prepared. All prepared dilutions in large series were tested on collection and clinical strains of microorganisms at an inoculum corresponding to a density of 3-6 x 10^/ml of live individuals. The test was incubated for 20 hours at 37°C and then the bacteriostatic effect was evaluated with simultaneous controls for positivity and negativity. The actual processing and evaluation was carried out with the help of Dynatech devices.

Microbiological evaluation was performed at the Department of Microbiology, Faculty of Medicine and Hygiene, Charles University in Prague.

Dermal irritation assessment - Research Institute for Biofactors and Veterinary Drugs Pohoří-Chotouň

The anesthetic activity of benzyl alcohol caused reduced irritation and therefore the presence of this substance in the preparation is necessary for this reason. In experiments where benzyl alcohol was omitted from the preparation for comparison, greater irritation was found both in preclinical tests on laboratory animals (rabbits) and in clinical tests on piglets.

The color intensity of the product guarantees reliable control of the application, both in terms of the serious work of the caretakers and the applied doses. The persistence of the color is guaranteed for 48-72 hours in normal stable conditions, and the marking on the back of the animals for even longer.

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240,070

Claims (3)

Object of the invention 240 070 A synergistic raicrobicidal composition, characterized in that, in addition to the usual excipients, it consists of 0.1% to 1.0% by weight of bromide and / or chloride, carbethopendecinium, 0.1% to 2.0% by weight of methyl violet and 2.0% to 20% by weight. % By weight of benzyl alcohol. 2. The composition of claim 1, wherein the weight ratio of the active ingredients in the above order is 0.5: ; 0,3 í 10. * Printed by Moravske tiskarske zavody, Price: 2,40 Kčs provoz- 12, cl. 3, Olomouc