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Author (s):Dolgintsev Maxim E. (RU), Bobyntsev Igor Ivanovich (RU), Smakhtin Mikhail (RU), Alexey Kryukov (RU), Olga I. Ivanov (RU), Andrey E. White (RU)
Patentee (s):State educational institution of higher education "Kursk State Medical University, Federal Agency for Health and Social Development" (RU)
Address for correspondence:305041, Kursk, str. Marx, 3, KSMU, the patent department, ZN Kupriyanova
Priorities:
submission of application:
12.04.2010
the beginning of the patent:
12.04.2010
Patent Publication:
20.06.2011
 

The invention relates to medicine, namely to the physiology and pathophysiology. The invention consists in the use of the peptide Gly-His-Lys, having the formula: (NH 2) Gly-His-Lys (COOH), for an analgesic effect in the pain caused by thermal stimulation. The invention allows the use of a new purpose-known peptide Gly-His-Lys with a pronounced analgesic effect. Table

PATENT

The invention relates to medicine, namely to the physiology and pathophysiology, and can be used for an analgesic effect in the pain caused by thermal stimulation.

In the literature, many authors described the properties of the peptide Gly-His-Lys. Known for its modulating effect in the regulation of cell growth and differentiation (Kato K., Kasai S., Onodera K. et al. Effect of hepatocyte growth factor on the proliferation of transplanted hepatocytes in the spleen. / / Transplant. Proc. - 1997. - Vol.29, № 4. - P.2029-2031; Sporn MB, Roberts AB Transforming growth factor-in: recent progress and new challenges. / / J. Cell Biol. - 1992. - Vol.119, № 5. - P.1017-1021). Several studies have confirmed the effect of the peptide as a stimulator of wound healing, as is known for its stimulating effect on collagen synthesis by fibroblasts (Maquart FX, Bellon G., Chaqour V. et al. In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L- histidyl-L-lysine-Cu2 + in rat experimental wounds. / / J. Clin. Invest. - 1993. - Vol.92, № 5. - P.2368-2376). It is shown that Gly-His-Lys promotes stimulation of physiological and reparative regeneration of the liver (Smakhtin MY, sewing IA, Hemp AA Bobyntsev II method for stimulating physiological and reparative regeneration of the liver. - Patent for invention number 2214269, of 20.10.2003). Known as a stimulating effect on hair growth peptide (Trackhy RE, Fors TD, Pickart L., Uno H. The hair follicle-stimulating properties of peptide copper complexes. Results in C3H mice / / Ann. N.-Y. Acad. Sci. - 1991. - Vol.642, № 10. - P.468-469) and anti-inflammatory effect associated with a decrease in iron release from ferritin in the damaged tissues (Miller DM, DeSilva D., Pickart L., Aust SD Effects of glycyl- histidyl-lysyl chelated Cu (II) on ferritin dependent lipid peroxidation / / Adv. Exp. Med. Biol. - 1990. - Vol.264. - P.79-84.).

The object of the invention is the use of a new purpose peptide Gly-His-Lys, having the formula: (NH 2) Gly-His-Lys (COOH), for an analgesic effect in the pain caused by thermal stimulation.

The task of the invention is achieved by applying the peptide Gly-His-Lys to an analgesic effect in the pain caused by thermal stimulation. Currently, as accurately known chemical formula of the peptide, it can be synthesized in any laboratory synthesis of peptides or purchased from companies engaged in the supply of biologically active compounds (Sigma, ICN, Merk, Bachim etc.). We used the drug, synthesized in the Institute of Chemistry at St. Petersburg State University. Dissolved in isotonic sodium chloride peptide Gly-His-Lys administered to experimental animals (mice), parenteral (i.p.) once daily doses of 0.5 and 5 mg / kg body weight 12 minutes before the onset of the pain stimulus.

Example of a specific implementation.

The experimental animals (male mice lines BALB / c) weighing 20-25 g were divided into groups of 10 animals each (Table). The animals were kept at a room temperature 22-24 C °, light regime: 12 hours - light, 12 hours - darkness and received standard pelleted food and water freely available.

In the experiment, the temperature sensitivity to pain can be estimated on the method of "hot plate" (Sernov LN Gatsura V. Elements of Experimental Pharmacology. - M., 2000. - 352.). In this method, an increase in the latent period of the reaction licking paws indicates the presence of an analgesic effect.

To examine sensitivity to pain during thermal exposure, mice were placed on a glass plate with excess cylinder heated to a temperature of 55 ° C. Test 4 was carried out for 1 minute at intervals of 1 min. Pain sensitivity was evaluated by the magnitude of the latent period (in seconds) reaction licking paws in the 2nd test.

The peptide Gly-His-Lys were dissolved in isotonic sodium chloride solution to obtain the required dose - 0.5 and 5 mg / kg animal body weight. Parenterally administered (i.p.) once the volume of experimental animals obtained the rate of 1 ml per 1 kg body weight (0.1 mL) for 12 minutes prior to a painful stimulus. Control animals received equivalent volume of saline (FR).

When using the peptide Gly-His-Lys at doses of 0.5 and 5 mg / kg of the analgesic effect is observed (table).

Latent period (in seconds, M ± m) pain reaction licking paws during thermal stimulation
Reaction

Group of animals
Lick
Introduction DF (control)18,0 ± 2,4
Introduction Gly-His-Lys at a dose of 0.5 mg / kg25,6 ± 1,9 *
Introduction Gly-His-Lys dose of 5 mg / kg23,6 ± 1,3 *
Note: * - p <0.05 compared with control group.

Thus, the results of experimental studies have shown that the use of the peptide Gly-His-Lys at doses of 0.5 and 5 mg / kg caused a pronounced analgesic effect in the pain provoked by thermal stimulation. This method is based on the use of regulatory peptides, belonging to the class of biologically active substances with a pronounced and polyfunctional modulatory effect is not tedious and does not require the use of complex equipment.


CLAIMS

Use of the peptide Gly-His-Lys, having the formula: (NH 2) Gly-His-Lys (COOH) for the analgesic effect in the pain caused by thermal stimulation.

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