Treatment of aspergillosis in rabbits

 

(57) Abstract:

The invention relates to veterinary medicine, in particular to methods for treating visceral mycosis rabbits, caused by a pathogenic fungus of the genus Aspergillus fumigatus. The technical result - the simplification of the way when the extension class of drugs for the treatment of aspergillosis rabbits. The method is as follows. Preparing a medicinal product with a content of 100 mg of mebendazole in 1 ml of water, the drug is administered to rabbits in a volume of 2-3 ml subcutaneously in the shoulder area once a day for 2-3 days in a row on 2-3rd day from the disease. 1 C.p. f-crystals, 4 PL.

The invention relates to veterinary medicine, in particular to methods for treating visceral mycosis rabbits, caused by a pathogenic fungus of the genus Aspergillus fumigatus.

Currently, there is a method of treatment of aspergillosis with mass lesions using aerosols containing iodine preparations. The aerosol is sprayed into the room at 1 m320 ml of 0.5% solution of iodine within 5-6 days (see Treatment and prevention of aspergillosis. C. C. Petrovich in the book. Mycosis animals. Moscow. Rosagropromizdat, 1989, S. 93).

However, therapeutic efficacy of this drug are minor, the method is General introduction nystatin dose 10000-15000 UNITS per 1 kg of live weight 3-4 times daily for 7-9 days in a row (see Worms D. K. Evdokimov P. D. Wicker A. S. Drugs in veterinary medicine, M. Kolos", 1966, S. 322-323).

However, the application of nystatin with aspergillosis ineffective, because nystatin is mainly on yeast-like fungi, practically not absorbed from the gastrointestinal tract. In addition, the treatment course is long.

Closest to the claimed technical solution is a method of treatment of aspergillosis with use as a medicinal product 30% solution of sodium thiosulfate and 20% solution of caffeine sodium benzoate. Sodium thiosulfate is administered 2 times a day for two days in a row for 20-30 ml inside, and caffeine sodium benzoate injected once a day for 5-10 ml (see Microflora of concentrated feed and toxicosis fungi of the genus Aspergillyus. I., Arrests, M. A. Hantuchova, in Proc. of the scientific, Tr. Pharmacology and toxicology of new drugs and feed additives in veterinary medicine. Leningrad, 1990, S. 96-98).

However, this method is time-consuming, as it involves the combination of a specific therapy with symptomatic treatment. In addition, the introduction of a solution of sodium thiosulfate inside the difficult doable.

The technical result of the simplification of the way when expanded the query result is achieved by in the treatment of aspergillosis, which consists in the introduction of a medicinal product, as the last drug use on the basis of mebendazole, which is injected subcutaneously once a day 2-3 days 2-3 days from the day of disease at a dose of 200-300 mg/goal.

As a preparation on the basis of mebendazole may be used either vermox or mibenum or megamin.

Vermox or mebendazole drug formula C16H13H3O3or methyl-5-benzylbenzimidazole-2-carbamate white slightly yellowish powder, practically insoluble in water and in most organic solvents. In the formic acid soluble. Molecular weight 295,29. Melting point 280oC (see, for example, the prospectus to the drug "Vermox" produced by the Chemical plant Gedeon Richter A. O. Budapest, Hungary).

Drug megamin is a similar vermoxe, white (sometimes with a faint creamy or pinkish tinge) fine crystalline powder, odorless. Megamin is an anthelmintic drug is less toxic than vermox, does not mutagenic effect. Synthesized in I. M. P. and T. M. them. E. I. marcinkowskiego USSR Ministry of health and Institute of chemistry restaurantsin chemical-pharmaceutical plant. Form release 0.1 g 10 tablets in cellular packaging.

Mibenum represents developed on the basis of mebenzadole antihelminthic drug specifically for vertical targets. The drug is produced by a Chemical plant Gedeon Richter A. O.

In well-known authors of the sources of patent and scientific and technical information not described method of treatment of aspergillosis by introducing a medicinal product on the basis of mebendazole (vermox, madamina or melanota). The mechanism of action of these drugs is based on the effect of mebendazole on helminths. This mebendazole both in vitro and in vivo prevents the absorption of glucose worms, and consumption of glucose mammals will not be affected even when used in high doses. (see sic Modical information brochure for Mebendasole; Lanssen Pharmacoutica H. V. Resarch Labora tories, Beerse, Belgium, 1972, I. Levai. Review of clinical pharmacological trial of mebendazole, 1974. Documentation of Chemical Plant Gedeon Richter (RGD 1647). Microscopic fungi of the genus Aspergillus for their carbohydrate metabolism intensively use large amounts of glucose. Given this feature of mushrooms for cultivation apply artificial nutrient medium, rich in carbohydrates (glucose and the Aspergillus due to the inability consumption of carbohydrates.

The method is as follows.

For the preparation of a medicinal product used an aqueous solution of madamina with a content of 100 mg of mebendazole in 1 ml of the Drug was administered to rabbits in a volume of 2-3 ml subcutaneously in the shoulder once a day 2-3 days 2-3 days from the day of disease.

Rationale fungicidal activity, timing, and dose of drug is given below.

Example 1. Rationale fungicidal activity of the drug.

Sensitivity to Aspergillus vermox, mebeletu and megamenu was determined on agar Petri dishes using paper disks impregnated with solutions of the tested drugs and then placed on the surface of seeded aspergilloma agar. Records of the results of antifungal activity of the drugs was performed after 24, 48, 72 and 96 hours of cultivation of mushrooms at 37oC on the first day and at the 22oC in the following.

The results of the antifungal activity of the tested drugs are presented in table. 1.

Characteristic for Aspergillus growth on glucose agar noticeable after 24 hours of cultivation. To 48-72 hour of colony growth of the fungus fill the entire surface of the Cup.

Disks impregnated pre is eriki growth Aspergillus was on cups with discs soaked madamina 30 mm. Thus, laboratory tests showed that the greatest fungicidal action had Madamin, the preparation of domestic production, more available for use in General practice.

Example 2. The rationale for the introduction of optimal doses of the drug.

To determine the optimal therapeutic doses of mebendazole was selected on the basis of analogues 38 rabbits, which were divided into 8 groups. The first 7 groups of experienced and 8th of control. Rabbits experimental groups were administered the drug in the following doses: 100, 150, 200, 250, 300, 350 and 400 mg/goal. 1 time per day 2-3 days. The animals were monitored for 7 days. Take into account for the duration and outcome of the disease. Rabbits died during the experience and murdered diagnostic purposes, examined postmortem and Ekologicheskie.

Data of the experiment are given in table. 2.

From the data table shows that the most optimal therapeutic doses of mebendazole at aspergillosis rabbits are 200-300 mg/goal.

The introduction of the drug in a daily dose of 300 mg/goal leads to unnecessary costs, not increase therapeutic effect and increases the volume of injected drugs, rendering RA is the party died in the abdominal cavity is detected characteristic aspergilloma, the kidneys also stripped hemorrhage, bladder full of urine mixed with blood. In smears from aspergillum when using the microscope revealed the mycelium of the fungus of the genus Aspergillus.

Example 3. Determining the optimal timing of the introduction of mebendazole in the treatment of aspergillosis rabbits shown in the table. 3, where on the basis of experimental data on the optimal timing and frequency of administration in 2-3 days after the onset of clinical signs of disease.

Example 4. The choice of method of administration of the drug is shown in the data table. 4.

These tables indicate that a significant difference in therapeutic efficacy of mebendazole at aspergillosis rabbits depending on the route of administration (subcutaneous or intramuscular) is not installed. We believe that the easiest to perform subcutaneous route of administration.

All recovered animals 7 days after infection were killed. Pathological picture was normal, except for animals 4-1 group, have kidney detected a faint aspergilloma, seeding them onto medium gave a negative result.

Thus, experimental studies on 61 kalekapisi fungi of the genus Aspergillus. The most effective was the domestic drug megamin.

The test results indicate a positive therapeutic effect of the treatment of aspergillosis rabbits.

1. Treatment of aspergillosis in rabbits by injection of a medicinal product, characterized in that the quality of drug use drug-based mebendazole, which is injected subcutaneously once a day for 2 to 3 consecutive days for 2 3 day of the disease at a dose of 200 - 300 mg/goal.

2. The method according to p. 1, characterized in that the quality of the drug on the basis of mebendazole use megamin.

 

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