RU2734899C1 - Use of an aqueous solution of protran 4-chloro-2-methylphenoxyacetate (chlorine crezacin) to stimulate static and dynamic operability - Google Patents

Abstract

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to biology and medicine, more specifically to biochemistry and pharmacology, and concerns application of aqueous solution of chlorine crezacin as a stimulator and static, and dynamic performance of transverse striated musculature. New property of chlorine crezacin is studied and described.

EFFECT: administering chlorine crezacin stimulates both static and dynamic operability.

1 cl, 1 tbl

Description

The invention relates to biology and medicine, specifically to biochemistry and pharmacology, and can be used to improve the performance of the striated muscles, for example, with fatigue, in sports, or with atrophy.

Muscle and nerve tissues play central roles in the realization of physical activity and the control of exercise tolerance limits. One of the basic processes in this case is an increase in the number and general metabolic activity of mitochondria, for example, myocytes. Among the known factors for stimulating mitochondrial functions, in addition to exercise and the use of caloric restriction of food, one can point to a number of drugs of natural origin - natural flavonoids, resveratrol, etc. [Rahman S. and Hanna M.G. Diagnosis and therapy in neuromuscular disorders: diagnosis and new treatments in mitochondrial diseases // J Neurol Neurosurg Psychiatry, 2009, 80: 943-953; Lira V.A., Benton C.R., Yan Z., Bonen A. PGC-lalpha regulation by exercise training and its influences on muscle function and insulin sensitivity // Am. J. Physiol. Endocrinol. Metab. 2010,299 (2): E145-161; Wallace D.C. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine //. Ann. Rev. Genetics 2005,39: 359-407; Saft C, Andrich J., Wieczorek S., Arning L., Taherzadeh-Fard E. PGC-lalpha as modifier of onset age in Huntington disease // Molecular Neurodegeneration, 2009, 4: 1750-1756; Lagouge M, Argmann C, Gerhart-Hines Z Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-lalpha. // Cell 2006; 127: 1109-1122].

However, there is a need for further research and the search for new effective drugs that provide optimal efficacy, specificity, and the absence of side effects. This draws attention to the triethanolammonium salts of aroxyacetic acids, which have a protatrane structure, reduce the damage to elastic fibers and stabilize cell membranes [Voronkov MG, Rasulov MM. Trekrezan - the founder of a new class of adaptogens and immunomodulators // Chem.-Pharm. Zh., 2007, No. 1, p. 3-9]. So, one of the representatives of a number of protatrans is zincatran, which looks like:

and the formula:

(HOCH ₂ CH ₂ ) 3N⋅Zn (OOCCH2OC6H4-CH3-2) 2

has the ability to improve performance [Rasulov M.M., Nurbekov M.K., Storozhenko P.A., Voronkov M.G., Abzaeva K.A., Snisarenko T.A., Susova M.I., Vaganov M. AND. Increase of efficiency // Patent for invention RU No. 2540476 dated March 27, 2014]. This allows zincatran to be used as a prototype for chlorocresacin.

The objective of the invention is to clarify the effectiveness of the use of chlorocresacin to increase both static and dynamic performance.

EFFECT: introduction of chlorocresacin stimulates both static and dynamic performance. This is achieved by using protatran 4-chloro-2-methyl-phenoxyacetate (chlorocresacin) in the form of pure for analysis (analytical grade) powder, which dissolves ex tempore in official distilled water, to improve performance.

Synthesized earlier [Voronkov MG, Adamovich SN, Mirskov RG, Mirskova AN. Synthesis of new biologically active O-hydrometalloatranes // ZhOKh, 2009, v.79, No. 1, pp. 162-163], biologically active compound - protatran 4-chloro-2-methyl-phenoxyacetate (chlorocresacin), has the form:

and the formula:

4-Cl-2-CH ₃ C ₆ H ₃ OCH ₂ COO ^- [NH (CH ₂ CH ₂ OH) ₃ ] ⁺

The novelty of the study lies in the fact that for the first time it was established that the administration of chlorocresacin stimulates performance. The new physiological activity of chlorocresacin to stimulate both static and dynamic performance has not been described in the literature.

The claimed biological activity of chlorocresacin was not known. Confirmation of the effectiveness of the use of protatran 4-chloro-2-methyl-phenoxyacetate (chlorocresacin) to improve performance, in comparison with the prototype, is demonstrated by the following data.

The object of the study is Wistar rats (n = 60) weighing 180-200 g. The rats are kept under standard conditions. The work is carried out in accordance with the "Rules of laboratory practice in the Russian Federation" approved by the order of the Ministry of Health of the Russian Federation of June 19, 2003 No. 267 (Rules of laboratory practice in the Russian Federation of the Ministry of Health of the Russian Federation Order of June 19, 2003 No. 267 http://www.kodeks.ru (April 24, 2010)). The animals are kept in accordance with the rules of the European Convention for the Protection of Vertebrate Animals used for experimental and other scientific purposes. Observations are carried out in the daytime (from 11 am to 3 pm).

The animals are divided into 4 groups: the first (15 rats) receives a solution of chlorocresacin in distilled water at the rate of 2 mg / kg of animal weight intraperitoneally for 7 days, the second (15 rats) receives a solution of chlorocresacin in distilled water at the rate of 5 mg / kg of weight animal intraperitoneally for 7 days. Immediately after the last injection, the animals are tested for static performance.

The third group (15 rats) receives a solution of chlorocresacin in distilled water at the rate of 2 mg / kg of animal weight intraperitoneally for 7 days and, finally, the fourth group (15 rats) receives a solution of chlorocresacin in distilled water at the rate of 5 mg / kg of animal weight intraperitoneally for 7 days. Immediately after the last injection, the animals are tested for dynamic performance.

Powder (analytical grade) protatran 4-chloro-2-methyl-phenoxyacetate (chlorocresacin) is mixed with official distilled water ex tempore until the powder is completely dissolved. According to the doses of the introduced substance, the ingredients are mixed as follows (wt.%).

for rats of the first and third groups:

distilled official water - 98

powder protatran 4-chloro-2-methyl-phenoxyacetate (chlorocresacin) - 2;

for rats of the second and fourth groups:

distilled official water - 95

powder protatran 4-chloro-2-methyl-phenoxyacetate (chlorocresacin) - 5.

Static performance is assessed by hanging rats on a horizontal grid screen. The rat is placed on a horizontal grid, smoothly released, the screen flips over, while the animal tries to hold on against the force of gravity. The animal remains hanging, catching on the net with its paws. The duration of the retention of the animal on the net is recorded. If the rat falls down within three minutes, it is placed back on the net, up to a total of three times. Calculate the total retention time for all three repetitions together, and the latency of the first fall [Holloway G.P., Bonen A., Spriet L.L. Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals // Am J Clin Nutr. 2009, 89 (1): 455S-462S].

The dynamic performance of animals is determined in the forced swimming test. Take into account the duration of swimming of rats with a load (8% of body weight) until the first signs of fatigue [Bobkov YG, Vinogradov VM, Katkov V.F. and other Pharmacological correction of fatigue. - M .: Medicine, 1984. - 208 p.].

Statistical data processing is carried out using generally accepted methods [Zaitsev GN. Mathematical analysis of biological data. - M .: Nauka, 1991. - 184 p.].

It should be noted that the authors previously conducted studies of the dose effects of the prototype (zincatran) in the range from 0.5 mg / kg to 15 mg / kg; however, in the dose range from 10 to 15 mg / kg, the effects of zincatran on performance did not differ.

Example

With the introduction of an aqueous solution of chlorocresacin at a dose of 2 mg / kg intraperitoneally, the performance of animals significantly increases. The use of an aqueous solution of chlorocresacin at a dose of 5 mg / kg enhanced this effect (Table 1).

Thus, with the introduction of an aqueous solution of chlorocresacin at a dose of 5 mg / kg intraperitoneally for 7 days, both static and dynamic performance significantly increase.

To obtain a more complete characterization of chlorocresacin and the possibility of facilitating a comparative analysis of the effects of chlorocresacin and zincatrane, it seems appropriate to provide in table 1 previously patented information on the effect of zincatrane on performance [Rasulov MM, Nurbekov MK, Storozhenko PL, Voronkov M.G., Abzaeva K.A., Snisarenko T.A., Susova M.I., Vaganov M.L. Improving performance // Invention patent RU No. 2540476 dated March 27, 2014].

Comparative analysis of the data shown in Table 1 allows us to conclude that chlorocresacin, used in doses half that of cincatran, has a more pronounced increase in both static and dynamic performance of animals.

Sources of information

1. Bobkov Yu.G., Vinogradov V.M., Katkov V.F. and other Pharmacological correction of fatigue. - M .: Medicine, 1984 .-- 208 p.

2. Voronkov M.G., Rasulov M.M. Trekrezan - the founder of a new class of adaptogens and immunomodulators // Chem.-pharm.Zh., 2007, №1, p. 3-9.

3. Voronkov M.G., Mirskova A.N., Rasulov M.M. Immunomodulatory efficacy of trerezan // Chemical-Pharmaceutical J., 2007, No. 5, p. 7-11.

4. Voronkov MG, Vlasova NN, Grigorieva O.Yu., A method of obtaining 2-methyl-4-halogen-phenoxyacetates of tris- (2-hydroxyethyl) ammonium (2-methyl-4-halogen-phenoxyacetoxyprotatranes. Patent No. 2427568 dated August 27, 2011, B.I. 24.

5. Zaitsev G.N. Mathematical analysis of biological data. - M .: Nauka, 1991 .-- 184 p.

6. Rasulov M.M., Nurbekov M.K., Storozhenko P.A., Voronkov M.G., Abzaeva K.A., Snisarenko T.A., Susova M.I., Vaganov M.A. operability // Patent for invention RU No. 2540476 dated March 27, 2014.

7. Holloway G.P., Bonen A., Spriet L.L. Regulation of skeletal muscle mitochondrial fatty acid metabolism in lean and obese individuals // Am J Clin Nutr. 2009, 89 (1): 455S-462S.

8. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-lalpha. // Cell 2006; 127: 1109-1122.

9. Lira V.A., Benton C.R., Yan Z., Bonen A. PGC-lalpha regulation by exercise training and its influences on muscle function and insulin sensitivity // Am. J. Physiol. Endocrinol. Metab. 2010, 299 (2): E145-161.

10. Rahman S. and Hanna M.G. Diagnosis and therapy in neuromuscular disorders: diagnosis and new treatments in mitochondrial diseases // J Neurol Neurosurg Psychiatry, 2009, 80: 943-953.

11. Soft C, Andrich J., Wieczorek S., Arming L., Taherzadeh-Fard E. PGC-lalpha as modifier of onset age in Huntington disease // Molecular Neurodegeneration, 2009, 4: 1750-1756.

12. Wallace D.C. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine // Ann. Rev. Genetics 2005,39: 359-407.

Claims (1)

Application of an aqueous solution of 4-chloro-2-methylphenoxyacetate (chlorocresacin) to stimulate static and dynamic performance.