RU2538692C1 - Method of treatment of endometritis in animals - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: method comprises the use of chemotherapeutic agents. The chemotherapeutic agent is used as N,N-dimethylamino-propylamides of fatty acids of the formula 1

which are used in the form of salts with pharmacologically acceptable acids.

EFFECT: use of the claimed invention is highly effective for treatment of endometritis in animals.

4 tbl, 2 ex

Description

The invention relates to the field of agriculture and veterinary medicine, and in particular to methods of treating endometritis in animals.

A known method of treating endometritis in animals with the use of probiotic agents (Novikova EN. Abstract for the candidate of veterinary sciences. Krasnodar, 2013).

There is a method of treating endometritis in animals using antibiotics and sulfonamides (Chervyakov D.K. et al. Medicines in veterinary medicine. Handbook, 1977, S. 296, 302, 304, 307, 328, 329, 331), we selected as prototype.

A known method of treating endometritis in animals using furazolidone sticks. The disadvantage of this method is the impossibility of introducing sticks with a sharp narrowing of the cervical canal (Reference. Veterinary drugs. Edited by A.D. Tretyakov. M: Agropromizdat, 1988, pp. 30-31).

The use of antibiotics, nitrofurans and sulfonamides for the treatment of endometritis is becoming less effective due to the emergence of resistant strains of microorganisms. In addition, in the treatment of endometritis in cows, milk is contaminated with antibacterial drugs, which in turn aggravates the situation with the ineffectiveness of antibiotic therapy not only in veterinary medicine, but also in medicine.

The aim of the invention is to develop a new effective method for the treatment of endometritis in animals.

This goal is achieved by the fact that as the active substance in the developed method for the treatment of endometritis in animals, amides of acids of the formula 1 are used (n = 14; 16), which are used in the form of salts with pharmacologically acceptable acids (hydrochloric, sulfuric, phosphoric, maleic, succinic and others):

The chemical name of compound 1 (n = 14) is palmitic acid (3-dimethylamino-propyl) amide.

The chemical name of compound 1 (n = 16): stearic acid (3-dimethylamino-propyl) amide.

Amides 1 are obtained from the corresponding acids 2 (n = 14; 16), according to the scheme:

An example of obtaining palmitic acid amide 1 (n = 14):

A mixture of 25.64 g (0.1 mol) of palmitic acid 2 (n = 14) and 10.21 g (0.1 mol) of amine 3 is heated at 150-155 ° C for 4 hours with distillation of volatile products, then at 170-175 ° C for 30 minutes also with distillation of volatile products. It is cooled and the resulting product 1 (n = 14) is purified by column chromatography on alumina in chloroform. Yield 33.37 g (98%), mp. 59-61 ° C.

¹ H NMR spectrum, CDCl ₃ (δ, ppm): 0.854-0.898 (3H, triplet); 1.248-1.273 (24H, multiplet); 1.567-1.681 (4H, multiplet); 2.112-2.163 (2H, triplet); 2.225 (6H, singlet); 2.346-2.388 (2H, triplet); 3.304-3.363 (2H, quartet); 6.927 (1H, singlet). Found,%: C 74.40; H 12.70; N, 8.05. Calculated,%: C 74.05; H 13.02; N 8.22.

An example of obtaining stearic acid amide 1 (n = 16):

Synthesize analogously to the palmitic acid amide from 28.44 g (0.1 mol) of stearic acid 2 (n = 16) and 10.21 g (0.1 mol) of amine 3. Yield 35.01 g (95%), so pl. 63-64 ° C. ¹ H NMR spectrum, CDCl ₃ (δ, ppm): 0.854-0.898 (3H, triplet); 1.186-1.249 (28H, multiplet); 1.568-1.712 (4H, multiplet); 2.113-2.164 (2H, triplet); 2.225 (6H, singlet); 2.346-2.388 (2H, triplet); 3.304-3.363 (2H, quartet); 6.928 (1H, singlet). Found,%: C 74.60; H 13.20; N, 7.63. Calculated,%: C 74.93; H 13.12; N, 7.59.

The obtained amides of acids 1 (n = 14; 16) are used as antibacterial and protistocidal agents in the treatment of endometritis in animals.

Example 1. The antibacterial and protistocidal activity of (3-dimethylamino-propyl) palmitic acid amide (n = 14) and (3-dimethylamino-propyl) stearic acid amide (n = 16) (see table 1):

Table 1 Antimicrobial activity No. p / p Connection number The minimum inhibitory concentration, mcg / ml St. aureus E. coli Colpoda steinii one Palmitic acid (3-dimethylamino-propyl) amide (n = 14) 6.25 6.25 5.8 2 Stearic acid (3-dimethylamino-propyl) amide (n = 16) 3,125 6.25 7.8 3 Furazolidone 6.25 3.8 > 1000

Example 2. The treatment of endometritis in animals

To this end, amide aqueous solutions are prepared. To dissolve amides in water, it is necessary to add the calculated amount (one equivalent) of pharmacologically acceptable mineral or organic acids (hydrochloric, sulfuric, phosphoric, succinic, citric and others), which play a secondary role, that is, contribute to the dissolution of amides in water, but do not have a therapeutic effect.

Apply 0.1% solutions of amides 1 (n = 14; 16) in terms of the free base. To prepare 10 liters of a working solution of 0.1% concentration (in terms of the free base), 10 g of the corresponding amide 1 (n = 14; 16) are weighed, mixed with 500 ml of water, one equivalent of acid is added, stirred at 40-50 ° C until a solution forms and the volume is adjusted to 10 liters. Tables 2 and 3 show the amounts of acid for amide 1 (n = 14; 16).

table 2 The amount of acid required to prepare 10 liters of a 0.1% solution of palmitic derivative 1 (n = 14) Salt Maleic Sulfuric Hydrogen bromide Sorbic 1.42 g in terms of HCl 2.26 g 1.91 g 3.15 g in terms of HBr 4.38 g

Table 3 The amount of acid required to prepare 10 liters of a 0.1% solution of stearic derivative 1 (n = 16) Salt Maleic Sulfuric Hydrogen bromide Sorbic 1.28 g in terms of HCl 2.03 g 1.72 g 2.84 g in terms of HBr 3.94 g

The cows of the experimental groups were injected into the uterus with a 0.1% aqueous solution of palmitic amide and stearic amide in the form of salts with mineral and organic acids in a volume of 100 ml through a probe using a Janet syringe. The cows of the control group were injected with furazolidone bacilli as an antibacterial agent.

To enhance the contractile function of the uterus and remove pathological exudate from the uterine cavity, sick cows of all groups were administered intramuscularly with 1% sinestrol solution followed by the administration of oxytocin.

Recovery was judged by the general condition of the animals, normalization of body temperature, the absence of vaginal discharge, and hematological parameters. Comparative effectiveness was assessed by the percentage of recovered animals. The test results are presented in table 4.

Table 4 The test results of the therapeutic efficacy of salts of fatty acid amides 1 (n = 14; 16) in the form of 0.1% aqueous solutions No. of groups of animals A drug The number of animals in the group on the 1st day of treatment The number of sick animals in the group on the 7th laziness of treatment The percentage of recovery in the group% one Palmitic acid amide 1 (n = 14) as a salt with hydrochloric acid. 17 2 88.2 Palmitic acid amide 1 (n = 14) as a salt with sulfuric acid 12 2 83.3 3 Palmitic acid amide 1 (n = 14) as a salt with sorbic acid 17 one 94.1 four Stearic acid amide 1 (n = 16) as a salt with hydrochloric acid 12 0 100.0 5 Control group 34 fourteen 58.8

From the data of table 4 it is seen that the effectiveness of treatment of animals in the experimental group using a 0.1% solution of palmitic acid in the form of salts with hydrochloric, sulfuric and sorbic acids on the seventh day of treatment is 83.3-94.1%. The use of a 0.1% solution of stearic acid amide as a salt with hydrochloric acid ensured the recovery of all cows in the group on the seventh day of treatment. Thus, the therapeutic effectiveness of the proposed method significantly exceeds the effectiveness of the treatment of animals in the control group (58%).

According to the study of therapeutic efficacy, we can also conclude that the type of acid used does not affect the therapeutic effect.

"Acute" toxicity of substances.

It was found that the introduction into the stomach of laboratory rats of 5% aqueous solutions of 3 ml of once palmitic acid amide 1 (n = 14), stearic acid amide 1 (n = 16) does not cause the death of laboratory rats. Signs of an acute toxic reaction in rats were not established within 10 days of observation.

The technical result that can be achieved by the implementation of this invention:

1. The range of chemotherapeutic agents used to treat animals with endometritis is expanding.

2. The effectiveness of treatment of animals with postpartum endometritis increases.

3. The recovery time of animals is reduced.

Literature

1. Veterinary drugs. Directory. Ed. HELL. Tretyakova. - M .: Agropromizdat, 1988, p.207-223.

2. Veterinary drugs. Directory. Ed. D.F. Osidze. M .: Kolos, 1981, p. 410-414.

3. Brains I.E. Antibiotics in veterinary medicine. - M .: Kolos, 1971, p. 75-83.

Claims (1)

A method of treating animals with endometritis, including the use of chemotherapeutic agents, characterized in that N, N-dimethylamino-propylamides of fatty acids of the formula 1 are used as a chemotherapeutic agent (n = 14; 16):

which are used in the form of salts with pharmacologically acceptable acids.