New Drugs for Ophthalmology Based on 6-methyl-3-(thietan-3-yl)uracil (Experimental Research)

Purpose: develop of new drugs for ophthalmology based on 6-methyl-3-(thietan-3-yl)uracil and methyluracil.

Materials and methods. An experimental study was carried out on 10 rabbits with a body weight of 3.5–4.0 kg of chinchilla breed. A thermal burn of the cornea in the eyes of 6 rabbits and a chemical burn of the cornea in the eyes of 4 rabbits were modeled. Therapy with the use of drugs was carried out: ophthalmic ointment — in thermal burns, ophthalmic medicinal films based on 6-methyl-3-(thietan-3-yl)uracil and methyluracil in chemical burns.

Results. The use of ophthalmic ointment based on 6-methyl-3-(thietan-3-yl)uracil for thermal burns led to a decrease in conjunctival hyperemia and resorption of corneal edema by 4–5 days. On the 14th day of therapy, the microscopic picture of the rabbits cornea had the usual normal structure. The use of 6-methyl-3-(thietan-3-yl)uracil and methyluracil based ophthalmic drug films yielded the following results: centripetal epithelialization of corneal erosion was observed, epithelial regeneration was higher with the use of methyluracil eye drug films and total epithelization was achieved on the 7th day of observation than when using eye drug films based on 6-methyl-3-(thietan-3-yl)uracil, where total epithelization occurred on the 14th day. Complete restoration of the surface epithelial layer of the cornea in both groups was observed on the 21st day.

Conclusions. The use of new drugs based on 6-methyl-3-(thietan-3-yl)uracil and methyluracil in various types of corneal burns showed good tolerance in the eyes of experimental animals, shortened the treatment time, and achieved high wound healing efficacy. 

1. Di Girolamo N. Moving epithelia: Tracking the fate of mammalian limbal epithelial stem cells. Prog Retin Eye Res. 2015;48:203–225. DOI: 10.1016/j.preteyeres.2015.04.002

2. Guide on laboratory animals and alternative models in biomedical research. Ed. by N.N. Karkishhenko, S.V. Grachev. Moscow: Profil’-2S; 2010. 358 р. (In Russ.).

3. Ernest P., Rhem M., McDermott M. Phacoemulsification conditions resulting in termal wound injury. J. Cataract Refract. Surg. 2001;27:1829–1839. DOI: 10.1016/s0886-3350(01)00908-7

4. Olson M.D., Miller K.M. In-air thermal imaging comparison of Legacy. Journal of Cataract and Refractive Surgery. 2005;31:1640–1647. DOI: 10.1016/j.jcrs.2005.01.016

5. Kerimov K.T., Dzhafarov A.I., Gahramanov F.S. Eye burns: pathogenesis and treatment. Moscow; 2005. 464 p. (In Russ.).

6. Obenberger J. Paper strips and rings as simple tools for standartization of experimental eye injuries. Ophthalmol. Res. 1975;7:363–367.

7. Kanjukov V.N., Stadnikov A.A., Trubina O.M., Jahina O.M. Experimental modeling of traumatic injuries of the cornea. Annals of Orenburg State University = Vestnik Orenburgskogo gosudarstvennogo universiteta 2014;12(173):156–159 (In Russ.).

8. Kataev V.A., Meshcherjakova S.A., Munasipova D.A., Nikolaeva K.V., Nurgaleeva E.A., Farhutdinov R.R., Petrova I.V., Kil’dijarov F.H. 6-methyl-1(thietanyl-3) uracil, which stimulates the protective activity of phagocytes. Patent RU 2485118. 2012 (In Russ.).

9. Meshherjakova S.A., Kataev V.A., Fattahova I.Ja., Nikolaeva K.V., Bulgakov A.K. Synthesis and antimicrobial activity of acetanilides and acetylhydrazones of thietanylpyrimidine-2,4 (1H, 3H) -dione series. Pharmaceutical Chemistry Journal = Himiko-farmacevticheskiy zhurnal. 2015;49(9):28–31(In Russ.).

10. Suzuki K., Saito J., Yanai R., Yamada N., Chikama T., Seki K., Nishida T. Cell-matrix and cell-cell interactions during corneal epithelial wound healing. Prog Retin Eye Res. 2003 Mar;22(2):113–133. DOI: 10.1016/s1350-9462(02)00042-3