EA021130B1 - Use of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-oxy-6-bromeindole and salts thereof for prevention and/or treatment of infectious diseases in animals of virus genesis - Google Patents

Abstract

The invention relates to veterinary, in particular, to a method of prevention and/or treatment of viral diseases in animals by using 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-oxy-6-bromeindole and salts thereof and can be used mainly in commercial livestock. The invention is aimed at providing therapeutic effectiveness of prevention and treatment of infectious diseases in animals of virus genesis. The assigned task is solved by using 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-oxy-6-bromeindole and salts thereof having antiviral and immunomodulating activity in veterinary and also by a method of prevention and/or treatment of viral diseases in animals, comprising parenteral and/or oral administration to animals of a preparation based on 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-oxy-6-bromeindole and salts thereof in an amount of 1.5-10 mg per a kg of animal weight by one or two courses lasting from 10 to 20 days.

Description

The invention relates to veterinary medicine, and in particular to a method for the prevention and / or treatment of animal viral diseases by the use of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4dimethylaminomethyl-5-hydroxy-6-bromoindole and its salts, and can be used mainly in livestock industry.

At the present stage of development of industrial animal husbandry, the most problematic are animal infectious diseases. For example, infectious diseases of pigs are combined according to the spectrum of clinical signs into the syndrome of post-weaning multisystem exhaustion of piglets caused by the association of several viruses. Several respiratory pathogens of both viral and bacterial nature are associated with the syndrome of multisystem post-weaning exhaustion of piglets. The most frequently found in this connection are type II circovirus, reproductive and respiratory syndrome virus, swine flu virus, porcine parvovirus, Musoritis lupus erythematosus, Acupunctus pyloriepithelium, and Papilliparas. The disease is characterized by a combination of clinical signs, including a progressive decrease in body weight, stunted growth, shortness of breath. With varying degrees of frequency, pallor and yellowness of the skin of animals, an increase in inguinal lymph nodes, an increase in body temperature, and diarrhea are observed. In vivo, signs of the disease are noted in 5-12 week old piglets. In different farms, the incidence of young animals is usually 5-20%, mortality is 80-100%. The frequency of the disease and the severity of its course are directly dependent on the number of animals on the farm.

Despite all kinds of restrictive measures and large-scale vaccination programs, there are no effective methods for the prevention and treatment of animals with the disease, post-weaning multisystem exhaustion of piglets. Preventive measures come down to a thorough disinfection of the premises, preventing the introduction of infected animals from dysfunctional farms and other quarantine actions. The implementation of this strategy to reduce the incidence of piglets and such sanitary and hygienic measures as early weaning of piglets from sows and fattening in groups selected by age have been unsuccessful in preventing viral diseases of the post-weaning period of piglets (B. Orlyankin, T. Aliper, E. Nepoklonov, Circovirus infection, Animal husbandry of Russia, 2003, No. 8; T. Drew, Post-weaning multisystem exhaustion syndrome: the role of pig circovirus in its etiology, Industrial and pedigree pig breeding, No. 4, 2005).

Known rotavirus infection in cattle (diarrhea of neonatal calves) is an acute contagious disease of newborn calves, characterized by damage to the gastrointestinal tract. The disease is widespread in all geographical regions of the globe. In practice, it was recorded everywhere where research was conducted. The causative agent of rotavirus infection in cattle is assigned to the Keousbae family, the genus Co1au1gi8. Rotavirus virions are spherical particles with a diameter of 65-75 nm, consisting of a core, inner and outer capsid. Infection is clinically manifested only in calves in the form of recurrent diarrhea. Calves become infected in the first hours after birth. Most often, the disease is recorded in late winter and early spring. The incidence reaches 90%, mortality - 20-50%.

Known 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole hydrochloride monohydrate (arbidol), exhibiting antiviral (against influenza viruses A and B) and immunomodulating activity (RF patents No. 2033156, 2008004, 2033157).

Medicines based on this compound are also known that are used to treat type A and B flu and acute respiratory diseases (RF patent No. 2240784) and for the treatment of SARS (RF patent No. 2256451).

Also known is 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole mesylate (RF patent No. 2255086) having a higher antiviral activity.

In medicine, preparations based on 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5oxy-6-bromoindole and its salts are mainly used in the form of solid dosage forms (tablets) with a bioavailability of about 40%.

The use in veterinary medicine of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy6-bromoindole and its salts is not described.

The objective of the invention is the provision of therapeutic efficacy in the prevention and treatment of infectious diseases of animals of viral origin.

The problem is solved by the use of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4dimethylaminomethyl-5-hydroxy-6-bromindole and its salts with antiviral and immunomodulating activity in veterinary medicine, as well as a method for the prevention and / or treatment of animal viral diseases, including parenteral and / or oral administration to animals of a preparation based on 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole or its salts in an amount of 1.5-10 mg per active ingredient per 1 kg of animal weight in one or two courses lasting from 10 to 20 days.

These preparations can be used in the form of solutions, emulsions, suspensions. 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole and its salts are poorly soluble in water. However, the use of certain solvents and technological methods allows one to obtain stable liquid dosage forms of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4dimethylaminomethyl-5-hydroxy-6-bromoindole and its salts in the form of injectable and oral solutions, suspensions and emulsions using carriers adopted in veterinary medicine for the preparation of means of delivery of the active component into the body of the animal. The solvents used are water purified for oral medicines, water for injections for parenteral medicines, propylene glycol, dimethylacetamide, dimethyl sulfoxide, dimethylformamide, метил-methylpyrrolidone, alcohols, polyethylene glycols, triglycerides, benzoic acid benzyl ester, glycerol formaldehyde olive, peach, apricot, almond), etc., as stabilizers - citric acid, ascorbic acid, hydrochloric acid, EDTA, sodium or potassium hydroxide, as there are two preservatives - benzyl alcohol, methylparaben, propylparaben, etc., and urea, hexamethylenetetramine, etc. as hydrotropic substances.

The mechanism of action of these drugs is associated with the suppression of viral reproduction, the effect on the synthesis of interferon, an increase in the number of T-lymphocytes and the functional activity of macrophages, as well as the antioxidant effect. 1-Methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5oxy-6-bromoindole inhibits the fusion of the lipid viral envelope with endosome membranes at pH 7.4, leading to the release of the viral genome and the beginning of transcription. Thus, 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole acts in the early stages of viral reproduction.

The therapeutic and prophylactic effectiveness of the use of preparations based on 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole and its salts is confirmed by the following examples.

Example 1

A 40% weaned piglet was tested with a 1% solution of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4dimethylaminomethyl-5-hydroxy-6-bromoindole hydrochloride in propylene glycol. 2 groups of 20 goals each were formed. The dose of the active substance was 2.0 mg per 1 kg of body weight. The specified solution was administered intramuscularly once for 10 days. The animals were clinically observed. In this case, the general clinical condition, the incidence of piglets in the post-dark period with respiratory and digestive diseases, the safety of piglets and the average daily gain in live weight were taken into account. The results are shown in table. one.

Table 1

Group of animals The mass of animals, kg Safety animals,% Incidence,% start of experience end of experience Control 27.0 ± 1.2 kg 31.5 ± 1.1 70 one hundred Experienced 27.1 ± 1.1 ct 32.9 ± 1.0 90 64

Example 2

Tests for rotavirus infection in cattle were performed. Studies were performed on 30 calves at the age of 2 weeks. Two groups of calves were formed: an experimental and a control group of 15 animals each. A 1% solution of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5oxy-6-bromoindole hydrochloride in propylene glycol was administered intramuscularly in an amount of 3.0 mg per 1 kg of live weight and at the same time a 2% solution of 1 -methyl-2-phenylthiomethyl-3-carbethoxy-4dimethylaminomethyl-5-hydroxy-6-bromoindole hydrochloride in propylene glycol was orally administered in an amount of 10 mg per 1 kg of body weight for 15 days. The results are shown in table. 2.

table 2

Group of animals The mass of animals, kg Safety animals,% Incidence,% start of experience end of experience Control 53.2 ± 1.8 kg 58.5 ± 1.6 66.7 one hundred Experienced 53.3 ± 1.7 kg 62.7 ± 1.7 93.3 60

Example 3

In 30 pigs, the injection solution was tested as a 1% solution of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole mesylate in a solvent consisting of 80% propylene glycol and 20% water for injection. 2 groups of 15 goals each were formed. The specified solution was administered intramuscularly at a dose of 2.5 mg per 1 kg of body weight for 20 days. Using this drug, it was possible to reduce mortality by 20%, as well as reduce the incidence from 100 to 67%.

Claims (2)

CLAIM 1. A method for the prevention or treatment of an infectious disease of viral origin in cattle or pigs, which consists in administering to the animal an intramuscularly solution of 1-methyl-2-phenylthiomethyl-3-carbetoxy-4-dimethylaminomethyl-5 -oxy-6-bromoindole propylene glycol or 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole hydrochloride 1 time per day for 10-20 days in the amount of 2.5-3.0 mg per 1 kg of body weight and at the same time 1% methyl-2-phenylthiomethyl-3-carbene propylene glycol solution is orally administered toxi 4-dimethylaminomethyl-5-hydroxy-6-bromoindole or 1-methyl-2-phenylthiomethyl-3-carbethoxy4-dimethylaminomethyl-5-hydroxy-6-bromoindole hydrochloride in an amount of 10 mg per 1 kg of animal body weight. 2. The method according to claim 1, characterized in that as a solvent for the preparation of a solution of 1-methyl-2-phenylthiomethyl-3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromindole and 1-methyl-2-phenylthiomethyl hydrochloride -3-carbethoxy-4-dimethylaminomethyl-5-hydroxy-6-bromoindole use a mixture of 80% propylene glycol and 20% water for injection.