Bìol. Tvarin. 2022; 24 (3): 14–17.
Received 26.05.2022 ▪ Accepted 28.07.2022 ▪ Published online 01.10.2022

Creation of combined stabilizing compositions to preserve the activity of gonadotropins in liquid form

O. V. Shtapenko1, I. I. Gevkan1, V. Y. Syrvatka2, O. Y. Slyvchuk1, O. O. Korbetska1, S. B. Kornyat1, I. M. Yaremchuk1

1Institute of Animal Biology NAAS,
38 V. Stusa str., Lviv, 79034, Ukraine, This email address is being protected from spambots. You need JavaScript enabled to view it.

2Ivan Franko National University of Lviv,
4 M. Hrushevskoho str., Lviv, 79005, Ukraine

The activity of dissolved enzyme preparations during storage decreases, what leads to the loss of their biological activity and, as a result, reduces the effectiveness of the drugs. Therefore, the development of compositions that are able to maintain high activity of the hormone in dissolved form during long-term storage is relevant. The results of studies have shown that using sucrose as a stabilizing component for maintain gonadotropin activity is effective. It was found that during eight weeks of storage the best results on the preservation of gonadotropin activity during storage at 40°C were obtained in samples containing 75 mg/ml of sucrose compared to the sample of the control group. However, the highest gonadotropin activity was found when — 10 mg/ml L-lysine and 75 mg/ml sucrose were used as stabilizers. Studies of the dynamics of gonadotropin activity during long-term storage at 18–20°C showed that the addition of L-lysine and sucrose as stabilizing substances in the form of liposomal emulsion increases the preservation of chorionic hormone activity for 2 weeks of storage by 11.4% compared to similar composition pharmacological composition of the drug in aqueous form.

Key words: human chorionic hormone, activity, stabilization, sucrose, mannitol, lysine

  1. Agostinetto R, Samaritani F. Del Rio A, Richard J. LH liquid formulations. Patent for invention no. US-8664369-B2 from 04.03.2014. Available at: https://pubchem.ncbi.nlm.nih.gov/patent/US-8664369-B2
  2. Choi J, Smitz J. Luteinizing hormone and human chorionic gonadotropin: distinguishing unique physiologic roles. Endocrinol. 2014; 30 (3): 174–181. DOI: 10.3109/09513590.2013.859670.
  3. Choi J, Smitz J. Luteinizing hormone and human chorionic gonadotropin: origins of difference. Cell Endocrinol. 2014; 383 (1–2): 203–213. DOI: 10.1016/j.mce.2013.12.009.
  4. Chu C, Li L, Li S, Li M, Ge S, Yu J, Yan M, Song X. Fluorescence-based immunoassay for human chorionic gonadotropin based on polyfluorene-coated silica nanoparticles and polyaniline-coated Fe3O4 Microchim. Acta. 2013; 180: 1509–1516. https://doi.org/10.1007/s00604-013-1067-7.
  5. Fernández-Tejada A, Vadola PA, Danishefsky SJ. Chemical synthesis of the β-subunit of human luteinizing (hLH) and chorionic gonadotropin (hCG) glycoprotein hormones. Am. Chem. Soc. 2014; 136 (23): 8450-8458. DOI: 10.1021/ja503545r.
  6. Fournier T. Human chorionic gonadotropin: Different glycoforms and biological activity depending on its source of production. Endocrinol. (Paris). 2016; 77 (2): 75–81. DOI: 10.1016/j.ando.2016.04.012.
  7. Griffin D, Feinn R, Engmann L, Nulsen J, Budinetz T, Benadiva C. Dual trigger with gonadotropin-releasing hormone agonist and standard dose human chorionic gonadotropin to improve oocyte maturity rates. Steril. 2014; 102 (2): 405–409. DOI: 10.1016/j.fertnstert.2014.04.028.
  8. Lawrenz B, Samir S, Garrido N, Melado L, Engelmann N, Fatemi H. Luteal coasting and individualization of human chorionic gonadotropin dose after gonadotropin-releasing hormone agonist triggering for final oocyte maturation — a retrospective proof-of-concept study. Endocrinol. 2018; 9: 33. DOI: 10.3389/fendo.2018.00033.
  9. Odintsova V, Bidnenko O. Selection of the excipients to create tablets of adamantane-1-ammonium 2-((5-(adamantane-1-yl)-4-phenyl-4h-1,2,4-triazole-3-yl)thio)acetate by the method of wet granulation. Part 1. ScienceRise: Pharm. Sci. 2017; 1 (5): 49–53. DOI: 10.15587/2519-4852.2017.93722.
  10. Pertsev I, Dmitrievsky, Rybachuk V. Excipients in Drug Technology: the impact on technological, consumer, economic characteristics and therapeutic efficacy. A textbook for students. Kharkiv, Golden Pages, 2010: 600 p. ISBN 978-966-400-178-3. (in Ukrainian)
  11. Schanz A, Lukosz M, Hess AP, Baston-Büst DM, Krüssel JS, Heiss C. hCG stimulates angiogenic signals in lymphatic endothelial and circulating angiogenic cells. Reprod. Immunol. 2015; 110: 102–108. DOI: 10.1016/j.jri.2015.01.011.
  12. Slyvchuk Y, Matiukha I, Syrvatka V, Hevkan I, Shtapenko O, Broda N. The influence of physical and chemical factors on HCG conservation activity for a long stored in the dilution state. ScienceRise: Biol. Sci. 2015; 11 (6/16): 18–22. DOI: 10.15587/2313-8416.2015.53805.
  13. Stolzenberger S., Kohler E. Liquid formulation of FSH. Patent for invention no. CN-101970010-A from 09.02.2011. Available at: https://testpubchem.ncbi.nlm.nih.gov/patent/CN-101970010-A

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