EXPERIMENTAL STUDY OF ANTIMICROBIAL PROPERTIES AND ACUTE TOXICITY OF THE PEO-BASED COMBINED SUPPOSITORIES

  • Tymur Ravshanov National University of Pharmacy, Ukraine
  • Ganna Zaychenko Bogomolets National Medical University, Ukraine
  • Kateryna Zhemerova SE "Ukrainian Scientific Pharmacopoeia Center for the Quality of Medicines", Ukraine
  • Volodymyr Zaychenko National University of Pharmacy, Ukraine
  • Olena Ruban National University of Pharmacy, Ukraine
Keywords: indole-3-carbinol, meloxicam, antimicrobial activity, acute toxicity

Abstract

Aim. The research of antimicrobial and toxicological parameters of a promising pharmaceutical composition with indole-3-carbinol and meloxicam in the form of rectal suppositories.

Materials and methods. The research of antimicrobial activity was carried out in vitro by diffusion in nutrient agar in the modification of "holes" on the reference strains of common pathogens Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, Candida albicans.

Adult rats were used for the study of acute toxicity. Suppository mass were administrated in the largest possible volume rectally or orally. The animals were periodically monitored according to the experimental plan – the assessment of physiological parameters before administration and after 6, 12, 18, 24 hours, at 3, 7 and 14 days. The animals were removed from experiment and necropsy provided after 1, 3, 7, and 14 days.

Results. The sizes of zones of inhibition of the microorganisms growth were most significant (from 19.27±0.61 mm of E. coli to 40.80±0.42 mm of S. aureus) near sample of the combined composition suppository compared with other combination of active substances and excipients.

During the observation of animals for 14 days and the study of internal organs after autopsy, deviations in physiological (weight, temperature, activity, respiratory rate) and macroscopic morphological indicators of animals from reference values were not detected.

Conclusion. According to the results of microbiological studies, a moderate antimicrobial effect of suppositories of combined composition in relation to all the studied pathogens was revealed. The absence of manifestations of acute toxicity allows us to conclude that the pharmaceutical composition can be classified as practically non-toxic substances.

The obtained results allow us to recommend a pharmaceutical composition with indole-3-carbinol and meloxicam on a polyethylene oxide basis in the form of suppositories for further preclinical studies of specific pharmacological effects as a prostate protective agent.

Downloads

Download data is not yet available.

Author Biographies

Tymur Ravshanov, National University of Pharmacy

Department of clinical pharmacology IPPQI

Ganna Zaychenko, Bogomolets National Medical University

Department of pharmacology

Kateryna Zhemerova, SE "Ukrainian Scientific Pharmacopoeia Center for the Quality of Medicines"

Laboratory of Pharmacopoeia Analysis

Volodymyr Zaychenko, National University of Pharmacy

Department of industrial technology of drugs

Olena Ruban, National University of Pharmacy

Department of industrial technology of drugs

References

Bradlow, H. L. (2008). Indole-3-carbinol as a chemoprotective agent in breast and prostate cancer. In vivo, 22 (4), 441–445.

Nachshon-Kedmi, M., Yannai, S., Haj, A., Fares, F. A. (2003). Indole-3-carbinol and 3,3′-diindolylmethane induce apoptosis in human prostate cancer cells. Food and Chemical Toxicology, 41 (6), 745–752. doi: http://doi.org/10.1016/s0278-6915(03)00004-8

Chinni, S. R., Li, Y., Upadhyay, S., Koppolu, P. K., Sarkar, F. H. (2001). Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells. Oncogene, 20 (23), 2927–2936. doi: http://doi.org/10.1038/sj.onc.1204365

Chinni, S. R., Sarkar, F. H. (2002). Akt inactivation is a key event in indole-3-carbinol-induced apoptosis in PC-3 cells. Clinical cancer research, 8 (4), 1228–1236.

Hsu, J. C., Zhang, J., Dev, A., Wing, A., Bjeldanes, L. F., Firestone, G. L. (2005). Indole-3-carbinol inhibition of androgen receptor expression and downregulation of androgen responsiveness in human prostate cancer cells. Carcinogenesis, 26 (11), 1896–1904. doi: http://doi.org/10.1093/carcin/bgi155

Reddy, G. P. V., Barrack, E. R., Dou, Q. P., Menon, M., Pelley, R., Sarkar, F. H., Sheng, S. (2006). Regulatory processes affecting androgen receptor expression, stability, and function: Potential targets to treat hormone-refractory prostate cancer. Journal of Cellular Biochemistry, 98 (6), 1408–1423. doi: http://doi.org/10.1002/jcb.20927

Sung, W. S., Lee, D. G. (2007). In Vitro Antimicrobial Activity and the Mode of Action of Indole-3-Carbinol against Human Pathogenic Microorganisms. Biological & Pharmaceutical Bulletin, 30 (10), 1865–1869. doi: http://doi.org/10.1248/bpb.30.1865

Ishiguro, H., Kawahara, T. (2014). Nonsteroidal Anti-Inflammatory Drugs and Prostatic Diseases. BioMed Research International, 2014, 1–6. doi: http://doi.org/10.1155/2014/436123

Canale, D., Scaricabarozzi, I., Giorgi, P., Turchi, P., Ducci, M., Menchini-Fabris, G. F. (2009). Use of a novel non-steroidal anti-inflammatory drug, nimesulide, in the treatment of abacterial prostatovesiculitis. Andrologia, 25 (3), 163–166. doi: http://doi.org/10.1111/j.1439-0272.1993.tb02701.x

Wang, W., Bergh, A., Damber, J.-E. (2004). Chronic inflammation in benign prostate hyperplasia is associated with focal upregulation of cyclooxygenase-2, Bcl-2, and cell proliferation in the glandular epithelium. The Prostate, 61 (1), 60–72. doi: http://doi.org/10.1002/pros.20061

Disilverio, F., Bosman, C., Salvatori, M., Albanesi, L., Proiettipannunzi, L., Ciccariello, M. et. al. (2005). Combination Therapy with Rofecoxib and Finasteride in the Treatment of Men with Lower Urinary Tract Symptoms (LUTS) and Benign Prostatic Hyperplasia (BPH). European Urology, 47 (1), 72–79. doi: http://doi.org/10.1016/j.eururo.2004.08.024

Minnery, C. H., Getzenberg, R. H. (2005). benign prostatic hyperplasia cell line viability and modulation of jm-27 by doxazosin and ibuprofen. Journal of Urology, 174 (1), 375–379. doi: http://doi.org/10.1097/01.ju.0000161598.24740.34

Bombardier, C., Laine, L., Reicin, A., Shapiro, D., Burgos-Vargas, R., Davis, B. et. al. (2000). Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis. New England Journal of Medicine, 343 (21), 1520–1528. doi: http://doi.org/10.1056/nejm200011233432103

Boehringer Ingelheim Pharmaceuticals. Mobic (meloxicam) tablets prescribing information (2006). Ridgefield, 10.

Choi, C. H., Moon, Y. S., Han, J. H., Lee, K. I., Kim, H. J. (2015). Pat. No. 14/414,883 USA. Composition comprising dendropanax morbiferaextract or compound derived therefrom as active ingredient for preventing and treating benign prostatic hyperplasia.

Carrabba, M., Paresce, E., Angelini, M., Galanti, A., Marini, M. G., Cigarini, P. (1995). A comparison of the local tolerability, safety and efficacy of meloxicam and piroxicam suppositories in patients with osteoarthritis: a single-blind, randomized, multicentre study. Current Medical Research and Opinion, 13 (6), 343–355. doi: http://doi.org/10.1185/03007999509110494

Ravshanov, T. B., Zaychenko, G. V., Zaychenko, V. S., Ruban, O. A. (2018). Farmakologіchne doslіdzhennya supozitorіiv dlya lіkuvannya dobroyakіsnih zahvoryuvan peredmіhurovoi zalozi. Web of Scholar, 1 (8 (26)), 51–57.

Stefanov, O. V. (2001). Doklіnіchnі doslіdzhennya lіkarskih zasobіv. Kiiv: Avіcena, 292–306.

Pharmacopoeia B. (2016). British pharmacopoeia.

European Pharmacopoeia Commission. European pharmacopoeia. Vol. 2. Maisonneuve.

U. S. Pharmacopeia. National Formulary USP 38 – NF 33. Rockville: The United States Pharmacopeial Convention. Available at: https://www.uspnf.com/official-text/proposal-statuscommentary/usp-38-nf-33

Volianskyi, Yu. L., Hrytsenko, I. S., Shyrobokov, V. P. (2004). Vyvchennia spetsyfichnoi aktyvnosti protymikrobnykh likarskykh zasobiv. Kyiv: Zdorovia, 38.

Khabriev, R. U., Verstakova, O. L., Arzamascev, E. V., Babaian, E. A., Belousov, Iu. B. et. al. (2005). Rukovodstvo po eksperimentalnomu (doklinicheskomu) izucheniiu novykh farmakologicheskikh veschestv. Otkrytoe akcionernoe obschestvo Izdatelstvo Medicina, 832.

Dacenko, B. M., Biriukova, S. V., Tamm, T. I. (1989). Metodicheskie rekomendacii po eksperimentalnomu (doklinicheskomu) izucheniiu lekarstvennykh preparatov dlia mestnogo lecheniia gnoinykh ran. Moscow, 45.

Semina, N. A., Sidorenko, S. V., Rezvan, S. P., Grudinina, S. A., Strachunskii, L. S. et. al. (2004). Opredelenie chuvstvitelnosti mikroorganizmov k antibakterialnym preparatam. MUK 4.2.1890-04. Moscow: Federalnii Centr Gossanepidnazora Minzdrava Rossii, 91.

Yevropeiska konventsiia pro zakhyst khrebetnykh tvaryn vid 1986 r. Available at: http://zakon5.rada.gov.ua/laws/show/994_137

Pro zakhyst tvaryn vid zhorstokoho povodzhennia (2006). Zakon Ukrainy No. 3447-IV. 21.02.2006. Vidomosti Verkhovnoi Rady Ukrainy, 27, 230.

Larianovska, Yu. B., Kotelevets, N. V. (2005). Morfostruktura peredmikhurovoi zalozy bilykh laboratornykh shchuriv. Medytsyna sehodnia y zavtra, 1, 12–14.

Glanc, S. (1999). Mediko-biologicheskaia statistika. Moscow: Praktika, 459.

Fiziologicheskie, biokhimicheskie i biometricheskie pokazateli normy eksperimentalnykh zhivotnykh (2013). Saint Petersburg: Izd-vo «LEMA», 116.

Meloksykam. Informatsiinyi fond «Derzhavnyi reiestr likarskykh zasobiv Ukrainy». MOZ Ukrainy. Available at: http://drlz.com.ua/

Shertzer, H. G., Sainsbury, M. (1991). Intrinsic acute toxicity and hepatic enzyme inducing properties of the chemoprotectants indole-3-carbinol and 5,10-dihydroindeno[1,2-b]indole in mice. Food and Chemical Toxicology, 29 (4), 237–242. doi: http://doi.org/10.1016/0278-6915(91)90020-8

Lehmann, H. A., Baumeister, M., Lützen, L., Wiegleb, J. (1996). Meloxicam: A toxicology overview. Inflammopharmacology, 4 (2), 105–123. doi: http://doi.org/10.1007/bf02735465

Nathan, A., Zalipsky, S., Ertel, S. I., Agathos, S. N., Yarmush, M. L., Kohn, J. (1993). Copolymers of lysine and polyethylene glycol: a new family of functionalized drug carriers. Bioconjugate Chemistry, 4 (1), 54–62. doi: http://doi.org/10.1021/bc00019a008


👁 389
⬇ 301
Published
2019-09-17
How to Cite
Ravshanov, T., Zaychenko, G., Zhemerova, K., Zaychenko, V., & Ruban, O. (2019). EXPERIMENTAL STUDY OF ANTIMICROBIAL PROPERTIES AND ACUTE TOXICITY OF THE PEO-BASED COMBINED SUPPOSITORIES. EUREKA: Health Sciences, (5), 12-20. https://doi.org/10.21303/2504-5679.2019.001000
Section
Medicine and Dentistry