Estimation of acute toxicity of a drug based on the complex of lithium citrate, polymethylsiloxane, aluminum oxide

Author: Korolev M.A.¹, Rachkovskaya L.N.², Madonov P.G.³, Shurlyginа A.V.⁴, Rachkovsky E.E.⁵, Letyagin A.Yu.⁶, Konenkov V.I.⁷, Churin A.A.⁸, Dubskaya T.Yu.⁹, Vetoshkina T.V.¹⁰, Sandrikina L.A.¹¹, Fomina T.I.¹², Fedorova E.P.¹³

Author Affiliations

¹Research Institute of Clinical and Experimental Lymphology – a branch of the Federal Research Center for Cytology and Genetics SB RAS 630060, Novosibirsk, Timakov str., 2

²Research Institute of Clinical and Experimental Lymphology – a branch of the Federal Research Center for Cytology and Genetics SB RAS 630060, Novosibirsk, Timakov str., 2

³Research Institute of Clinical and Experimental Lymphology – a branch of the Federal Research Center for Cytology and Genetics SB RAS 630060, Novosibirsk, Timakov str., 2

⁴Research Institute of Clinical and Experimental Lymphology – a branch of the Federal Research Center for Cytology and Genetics SB RAS 630060, Novosibirsk, Timakov str., 2

⁵Research Institute of Clinical and Experimental Lymphology – a branch of the Federal Research Center for Cytology and Genetics SB RAS 630060, Novosibirsk, Timakov str., 2

⁶Research Institute of Clinical and Experimental Lymphology – a branch of the Federal Research Center for Cytology and Genetics SB RAS 630060, Novosibirsk, Timakov str., 2

⁷Research Institute of Clinical and Experimental Lymphology – a branch of the Federal Research Center for Cytology and Genetics SB RAS 630060, Novosibirsk, Timakov str., 2

⁸Research Institute of Pharmacology and Regenerative Medicine. E.D. Goldberg, Tomsk National Research Medical Center 634028, Tomsk, Lenin str., 3

⁹Research Institute of Pharmacology and Regenerative Medicine. E.D. Goldberg, Tomsk National Research Medical Center 634028, Tomsk, Lenin str., 3

¹⁰Research Institute of Pharmacology and Regenerative Medicine. E.D. Goldberg, Tomsk National Research Medical Center 634028, Tomsk, Lenin str., 3

¹¹Research Institute of Pharmacology and Regenerative Medicine. E.D. Goldberg, Tomsk National Research Medical Center 634028, Tomsk, Lenin str., 3

¹²Research Institute of Pharmacology and Regenerative Medicine. E.D. Goldberg, Tomsk National Research Medical Center 634028, Tomsk, Lenin str., 3

¹³Research Institute of Pharmacology and Regenerative Medicine. E.D. Goldberg, Tomsk National Research Medical Center 634028, Tomsk, Lenin str., 3

Abstract

Research Institute of Clinical and Experimental Lymphology has developed an innovative drug based on a complex of lithium citrate, polymethylsiloxane and aluminum oxide (LOAP). Lithium-based drugs are effective in treating bipolar disorders. However, the toxic effects of lithium cause a “narrow therapeutic window”, which limits its clinical use. The creation of the drug LOAP was aimed at creating a prolonged form with a slow release of lithium to reduce toxic properties and use lithium citrate as an active pharmacological agent. At the moment, the lithium complex has no analogues. The purpose of the study was to study the parameters of acute toxicity of the LOAP. Material and methods. When studying acute toxicity, drugs were administered once intragastrically to mice and rats at doses of 12000, 10000, and 5000 mg/kg. Results. A single administration of drugs intragastrically through a probe in the maximum possible doses to mice and rats did not cause the death of animals and did not cause a locally irritating effect on the gastric mucosa. LOAP can be assigned to hazard class 4 (GOST 12.1.007-76).

Key words

lithium drugs, complex of lithium citrate, polymethylsiloxane and aluminum oxide, acute toxicity

References

World Health Organization. ICD-11 for Mortality and Morbidity Statistics: Bipolar or related disorders [Electronic resource]. Available at: https://icd.who.int/browse11/l-m/en. Access date: 05/12/2020.
Post R.M. The new news about lithium: an underutilized treatment in the United States. Neuropsychopharmacology. 2018; 43 (5): 1174-1179. doi: 10.1038/npp.2017.238
Öhlund L., Ott M., Oja S., Bergqvist M., Lundqvist R., Sandlund M., Renberg S.E., Werneke U. Reasons for lithium discontinuation in men and women with bipolar disorder: a retrospective cohort study. BMC Psychiatry. 2018; 18 (1): 37. doi: 10.1186/s12888-018-1622-1
Rybakowski J.K. Challenging the negative perception of lithium and optimizing its long-term administration. Front. Mol. Neurosci. 2018; 11: 349. doi: 10.3389/fnmol.2018.00349
Rachkovskaya L.N., Konenkov V.I., Parmon V.N., Borodin Yu.I., Letyagin A.Yu., Korolev M.A., Tertishnikov I.V. The method of obtaining carbon mineral sorbent. Patent RF № 2529535; publ. 27.09.2014. [In Russian].
Borodin Ju.I., Konenkov V.I., Parmon V.N., Ljubarskij M.S., Rachkovskaja L.N., Bgatova N.P., Letjagin A.Ju. Biological properties of sorbents and prospects for their application. Uspekhi sovremennoy biologii = Biology Bulletin Reviews. 2014; 134 (3): 236–248. [In Russian].
Chukin G.D. The structure of aluminum oxide and hydrodesulfurization catalysts. Mechanisms of reactions. Moscow: Printa, 2010. 288 p. [In Russian].
Rachkovskaya L.N., Popova T.V., Kotlyarova A.A., Michurina S.V., Shurlygina A.V., Rachkovsky E.E., Robinson M.V., Madonov P.G., Korolev M.A., Letyagin A.Yu. Vestnik Kyrgyzsko-Rossiyskogo Slavyanskogo univeriteta = Bulletin of the Kyrgyz-Russian Slavic University. 2019; 19 (1): 94-96. [In Russian].

9. Pronin A.V., Gromova O.A., Torshin I.Yu., Grishina T.R. Dynamics of lithium distribution in various tissues after oral administration of lithium citrate in rats. Farmakokinetika i farmakodinamika =Pharmacokinetics and pharmacodynamics. 2017; (4): 16-23. [In Russian].

10. Guidelines for conducting preclinical studies of drugs. Eds. A.N. Mironov, N.D. Bunatyan, A.N. Vasilyeva. Moscow: Grif i K, 2012. 944 p.

About Authors (Correspondence):

Shurlygina A.V., e-mail: anna_v_s@mail.ru

Full Text

snmzh_5-2020_korolev_i_dr.pdf

Received: 28/10/2020

Accepted: 28/10/2020