RU2762707C1 - Method for application of nicotinic and succinic acids and its salts as olfactory stimulants in dogs - Google Patents

Abstract

FIELD: veterinary pharmacology.

SUBSTANCE: group of inventions relates to the field of veterinary pharmacology, namely the use of nicotinic acid, succinic acid and its salt, iron dihydrate succinate, affecting cerebral circulation, reducing free radical processes and enhancing the sense of smell in animals. The use of succinic and nicotinic acids as a stimulant of smell in dogs is that succinic acid or nicotinic acid in a dose of 0.05 g for every 30 kg of weight is given orally 15 minutes before the intended use of a service dog. The use of iron dihydrate succinate as a stimulant of smell in dogs is that iron dihydrate succinate in a dose of 0.02 g per 30 kg of animal weight is given 15 minutes before the intended use of a service dog.

EFFECT: possibility of using nicotinic acid, succinic acid and its salt, iron succinate, having lower toxicity, as olfactory stimulators in dogs.

4 cl, 2 dwg, 3 tbl

Description

The invention relates to the field of veterinary pharmacology, namely, the use of chemical compounds - succinic and niacin, as well as iron salts of succinic and niacin, which affect cerebral circulation, reduce free radical processes and enhance the sense of smell in animals.

Nicotinic acid, vitamin PP, niacin - an antioxidant and antihypoxanth, is found in cereals, liver, is the main metabolite for the enzymes nicotinamide dinucleotide (NAD) and nicotinamide dinucleotide phosphate (NADP).

It is used as a biologically active additive in the complex treatment of cardiovascular diseases (E.P. Trukhacheva, M.P. Yezhov The value of nicotinic acid in modern cardiology / E.P. Trukhacheva, M.P. Yezhov // Rational pharmacotherapy in cardiology. - 2011. - No. 7 (3). - S. 365-370. [1]).

Succinic acid is an antihypoxant that is part of the main metabolic supplier - the Krebs cycle, which is present in all living cells.

Succinic acid effectively helps to eliminate acute hypoxic conditions: heart attack, stroke (Nikitina E.V., Romanova N.K. Succinic acid and its salts as individual antioxidants and gene protectors. Bulletin of Kazan Technological University, No. 10, 2010, S. 375- 381. [2]).

Iron (II) succinate dihydrate in accordance with acute toxicity was used in accordance with the recommendations (Hasanov A.S. Pharmaco-toxicological characteristics of the antianemic agent of iron succinate. Diss. ... Doctor of Biological Sciences. Kazan, 2006. 272 p. [3]

The prototypes of these antioxidants are fat-soluble vitamins - tocopherol (vitamin E) and retinol (vitamin A), which have the ability to bind radicals in the cytosol of cells, blood plasma, blood and lymph. Fat-soluble bioantioxidants mainly protect against peroxidation of the cell membrane.

The closest in technical essence and accepted as prototypes of stimulants of smell in dogs are the alkaloid caffeine and phenamine, which have a stimulating (adrenergic) effect on the central nervous system, increasing the frequency and strength of heart contractions, muscle tone [A.S. Mozzhukhin, 1946].

It is known that after taking substances that stimulate the nervous system (caffeine, ephedrine), the sensitivity of the human olfactory organ to the smell of ethyl alcohol and acetic acid increases (Krushinsky, L.V. nervous activity. - 1959. - T. 9. - Issue 2. - S. 3-7. [4]).

The objective of the invention is a method of using salts of nicotinic and succinic acid as stimulants of smell and compounds with lower toxicity than drugs - caffeine and phenamine.

A study of the effect of phenamine on conditioned reflexes in dogs and some other animals showed that this drug in optimal doses has a beneficial effect on higher nervous activity, while its large doses can cause disturbances in higher nervous activity [4]. A.I. Bronstein (1950), elucidating the effect of strychnine, caffeine, phenamine and pyramidone on the threshold for the perception of smell of substances such as coumarin, camphor and others, found that caffeine increases a person's sensitivity to smell by 15-20% and phenamine - by 35-55% ...

Phenamine is the most effective means for increasing the sensitivity of the human olfactory analyzer in comparison with other studied substances (caffeine, strychnine, etc.) (Bronstein, 1951, Sereisky, 1943) [4].

Instructions on the enhancement of the sense of smell in dogs under the influence of phenamine, caffeine and bromine are available in the work of D.A. Fless (1952) and N.M. Myznikova (1958) L.V. Krushinsky (1946) and D.A. Fless (1952) conducted a number of studies, as a result of which the dosages of the use of phenamine alone, as well as together with bromine and caffeine, were clarified. The optimal single dose of phenamine for different dogs was in the range of 0.01-0.02 g. Age within 1-7 years and gender did not have a determining value for the values of the optimal dose of phenamine, but the type of higher nervous activity played a certain role in this. So, in dogs with signs of weakness of the nervous system (periodic refusals during track work, fear of shots), the average dose of phenamine - 0.015 g was excessive. The introduction of phenamine to dogs that were poorly or insufficiently trained in the search service did not lead to a significant improvement in their tracking performance and, therefore, could not compensate for the lack of their training and training.

The effect of phenamine on sampling quality was found in several dogs. Phenamine was given to dogs 40-50 minutes prior to testing.

Phenamine markedly improved the quality of the dog's performance of an important technique of the search service - sampling.

As a result of exposure to these substances, the duration of the search increased, the tracking work and the quality of the sample in service dogs improved (Krushinsky, L.V. Service dog / L.V. Krushinsky, E.K. Merkuriev, I.E. - M .: State publishing house of agricultural literature, 1952. - 412 p. [5]).

Phenamine has a small latitude of therapeutic action and, in the event of an overdose, which can occur in the event of even a slight increase in the dose (10% higher than the therapeutic one), animals can die from arising cardiac disorders - tachycardia and extrasystoles. This seriously limits the possibilities of using such olfactory stimulants.

As you know, succinic acid is a substance belonging to the 5th class of toxicity that reduces the risk of neurosis. Succinic acid and its salts - succinates as part of a number of pharmaceuticals (Reamberin) are used in the complex rehabilitation therapy of diseases of neurological origin [6]. This substance promotes the regeneration and restoration of nerve cells.

Caffeine toxicity (LD ₅₀ ) 192 mg / kg (oral, mice). (Electronic resource: http://chemister.ru/Database/properties.php? Dbid = l & id = 728 (date of access: 14.10.2019, [7]).

The toxicity of phenamine (LD ₅ o) is 353 mg / kg (orally, mice) (orally, mice) (Electronic resource: www.xumuk.ru/spravochnik/199.html (access date: 12/14/2019), [8].

Toxicity of succinic acid (LD ₅₀ ) - 3400 mg / kg (orally, in mice) (Basankin A.V. Pharmaco-toxicological substantiation of the use of succinic acid in animal husbandry and veterinary medicine. Author's abstract of Ph.D. in veterinary science. 2007. KGAVM, Kazan, 23 with.) [9].

The source of succinic acid used tablets (Russia, production "Kvadrat-S"), containing 0.1 g for oral administration [10].

Succinic acid was used 15 minutes before the experiment in the amount of 50 mg / 30 kg of body weight of the dog orally, which is equivalent to the dose for humans in accordance with the body weight of 75 kg.

Nicotinic acid tablets (Russia, produced by JSC Pharmstandard-UfaVITA) containing 0.05 g of active ingredient [10].

The effect on the sense of smell was studied on 60 dogs of the German and Belgian Shepherd (Malinois) breeds by the method of pairs - analogues of 30 dogs of each breed for 2 years [11].

The experiment involved healthy dogs and only after being examined by a veterinarian. Groups of dogs - control and experimental - had equal skills and abilities, differed in age and sex.

In order to determine the effect of succinic acid on the sense of smell of dogs, the olfactory threshold was determined according to the method described by L.V. Krushinsky [5].

Succinic acid was fed to dogs with a treat after being examined by a veterinarian 15 minutes before starting to sniff cans. On a fixed board, there were five clean identical cans, which were plastic pipes of the same diameter, a piece of boiled pork 2 cm ³ in size was placed inside one of the cans. The cans were covered from above with filter paper, which was secured with an elastic band (Fig. 1). For the experiment, we chose White Ribbon filter paper, which corresponds to GOST 12026-76. The filtering capacity of the paper was no more than 45 s, the mass fraction of ash was no more than 0.2%. (Fig. 2).

After preparing the premises, a dog handler with a dog was launched into the office. First, the dog was released from the leash to get acquainted with the premises.

After that, the dog handler, standing 1.5-2 m from the cans, called the dog to him and, with a gesture of his right hand, directed the dog to sniff the cans on its own. The start was always carried out from one side.

As soon as the dog indicated the right can, the dog handler encouraged the dog and, attaching a leash, took it out of the room for a walk. At this time, the cans were thoroughly washed by another person with gloves, they were wiped, the amount of filter paper was added, the cans with the "filling" were changed places, after which the dog handler brought the dog up for the next start.

Restarting the dog continued until the dog stopped picking up odor particles and found a treat. If the dog spent more than 1 minute on finding the desired item, it was removed from the sample.

The dog handler took the dog out of the room, at that moment the banks changed places, and the dog started up again.

This procedure was repeated three control times with an interval of 7 days: on the 1st, 7th and 14th days. In the experimental group, dogs received succinic acid in an amount of 50 mg per 30 kg of the dog's live weight. At the end of the experiment, the dog handler walked the dog and put it in the containment area. On the second and third days, the substances were given to the dogs 15 minutes before passing through the cans. The assessment of the effect of succinic acid was carried out according to a qualitative indicator - the effectiveness of dogs in a sample of things and a quantitative indicator - the time spent on the search time. The search time that the dogs spent on the passage are given in the form of the arithmetic mean and standard deviation (σ).

The results of using succinic acid are shown in table 1.

The olfactory threshold in the control group changed by 32.65%, and in the experiment group by 51.92%. Under the influence of succinic acid in the experimental group, the time spent by the dogs for finding meat changed by 10.16%, and in the control group by 8.9%.

To determine the effect of nicotinic acid in a dose of 0.05 g on a dog weighing 35-40 kg was given 15 minutes before sampling things. Table 2 shows the results of the use of nicotinic acid on the olfactory activity of German Shepherds and Belgian Shepherds (Malinois) in the form of mean and standard deviation (σ).

There were minor changes in the control group. The intake of the declared substances is safer due to the greater breadth of the therapeutic effect than the intake of chemical compounds - prototypes (phenamine, caffeine). At the same time, the experimental group showed an increase in performance by 18.8%.

It was found that the time taken to sample a thing against the background of the use of nicotinic acid in dogs decreased by 21.6%, and the time in the control group decreased by 7.8%, which indicates the effective use of nicotinic acid as a stimulant of olfactory activity.

In order to determine the effect of iron succinate on the sense of smell, a human sample was performed in dogs. This experiment consisted in the fact that 7-10 people are in the ranks, and when sniffing these people, the dog finds objects in them, or the dog sets the person who hid the object that the dog is looking for.

The results of the effect of iron succinate on a sample of humans are shown in Table 3 as the arithmetic mean and standard deviation.

Dogs that received iron succinate were interested in sniffing, were less exposed to fatigue and, in terms of effectiveness, the increase in 14 days in a series of 3 experiments was 38.8%, and in the control group, the effectiveness in 14 days increased significantly less - by 13. one%. The search time was in the control group for 14 days decreased by 12.3%, and in the experience group by 29.2%. The group of dogs that received iron succinate worked more effectively.

The use of iron succinate as a stimulant of smell was carried out according to a similar scheme and at a dose of 0.02 g per dog weighing 35-40 kg (German and Belgian shepherd dogs).

Often, intense physical activity, some diseases of animals with a long latency period contribute to the formation of olfactory fatigue in dogs [12], iron salts are used to prevent iron deficiency anemia in dogs [13].

All of these factors are significant difficulties that lead to non-fulfillment or unsatisfactory fulfillment by the dog of the official tasks of searching for objects or a person.

Reception of the declared substances is safer due to the greater breadth of the therapeutic effect than the reception of chemical compounds - prototypes (phenamine, caffeine).

The task is achieved by the fact that 15 minutes before use in carrying out operational or routine measures to search for objects, substances and a person, a service dog is given nicotinic, succinic acid orally with a delicacy in a dose of 0.05 g / 30 kg of animal weight or ferric succinate dihydrate in dose of 0.02 g / 30 kg of animal weight.

Bibliography

1. Trukhacheva, E.P. The value of nicotinic acid in modern cardiology / E.P. Trukhacheva, M.P. Yezhov // Rational pharmacotherapy in cardiology. - 2011. - No. 7 (3). - S. 365-370.

2. Nikitina E.V., Romanova N.K. Succinic acid and its salts as individual antioxidants and gene protectors. Bulletin of Kazan Technological University, no. 10, 2010, pp. 375-381.

3. Hasanov A.S. Pharmaco-toxicological characteristics of the antianemic agent of iron succinate. Diss. ... Doctor of Biological Sciences. KGAVM, Kazan, 2006.272 p.

4. Krushinsky, L.V. Artificial enhancement of the sense of smell in service dogs / L.V. Krushinsky // Journal of Higher Nervous Activity. - 1959. - T. 9. - Issue. 2. - S. 3-7.

5. Krushinsky, L.V. Service dog / L.V. Krushinsky, E.K. Merkuriev, I.E. Izrailevich [and others] - M .: State publishing house of agricultural literature, 1952. - 412 p.

6. Rumyantseva S.A. Complex antioxidant therapy with Reamberin in the complex therapy of patients with diseases of nervous genesis / S.A. Rumyantseva // Reamberin: reality and prospects, collection of articles. scientific. articles, St. Petersburg, 2002, pp. 74-98.

7. Electronic resource: www.xumuk.ru/spravochnik/199.html (date of access: 12/14/2019).

8. Basankin A.V. Pharmaco-toxicological substantiation of the use of succinic acid in animal husbandry and veterinary medicine. Abstract of thesis ... for a Candidate of Sciences vet. sciences. 2007. KGAVM, Kazan, 23 p.

9. Electronic resource: https://www.rlsnet.ru/mnn_index_id_1023.htm (date of access: 12/14/2019).

10. Guidelines for experimental (preclinical) study of new pharmacological substances. M. 2000.155 p.

11. Koptev V.V. Fundamentals of Scientific Research and Patent Science: for agriculturalists. universities engineer. and an agronomist. specialties / Koptev V.V., Bogomyagkikh V.A., Trifonova M.F. - M .: Kolos, 1993 .-- 144 p.

12. Wright, P. X. The Science of Smells. - M .: Mir, 1966 .-- 221 p.

13. Kononova N.Yu., Zukhrabov M.G. Comparative efficacy of chelavit and ferrous succinate preparations for the prevention of iron deficiency anemia in pregnant bitches. Scientific notes of the Kazan State Academy of Veterinary Medicine. N.E. Bauman, T. 207, no. 3, 2011, pp. 293-297.

Claims (3)

1. The use of succinic acid as a stimulant of smell in dogs is that succinic acid at a dose of 0.05 g for every 30 kg of weight 15 minutes before the intended use of a service dog with a treat is given orally. 2. The use of nicotinic acid as a stimulant of smell in dogs is that 15 minutes before the intended use of a service dog with a treat, they are given orally in a dose of 0.05 g for every 30 kg of animal weight. 3. The use of ferric succinate dihydrate as a stimulant of smell in dogs is that ferrous succinate dihydrate at a dose of 0.02 g per 30 kg of animal weight is given 15 minutes before the intended use of a service dog with a treat.

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