Comparative assessment of the osmotic and anti-inflammatory activity of soft dosage forms of pyrimidine drugs on hydrophilic bases in an experiment

Abstract

BACKGROUND: Despite the constant search for new medications for local prevention of surgical infection, the problem of purulent-inflammatory complications from postoperative soft tissue wounds remains relevant to this day.

AIM: To experimentally study the osmotic activity and anti-inflammatory properties of the developed xymedone-containing ointment composition levoxycol in comparison with the well-known ointment dioxomethyltetrahydropyrimidine + chloramphenicol (levomekol).

MATERIAL AND METHODS: The anti-inflammatory properties of the ointments were studied in vivo on 60 outbred male Wistar rats, which were divided into three groups, 20 animals each. The first group served as control. In the second group of animals, levomekol ointment was used, in the third group — levoxycol. An assessment of the osmotic activity of the experimental ointment composition levoxycol in comparison with a known drug was carried out in an in vitro experiment. To evaluate the anti-inflammatory activity of ointments, a model of carrageenan-induced edema of rat paws was used. To analyze differences in the frequency of the studied outcomes in groups of animals, the Mann–Whitney U test was used.

RESULTS: Osmotic activity showed that wipes soaked in ointment forms absorbed the following amount of contrast (Me [Q₁; Q₃]): levomekol — 28.2 (26.4; 31.3) ml; levoxycol — 41.8 (39.5; 43.4) ml (p=0.001). The anti-inflammatory activity of the ointment forms manifested itself in the form of suppression of swelling of the rats' paws at 3 and 5 hours after the injection of carrageenan. When using the ointment form of levomekol, the volume of displaced liquid with the introduction of carrageenan, starting from 3 hours, was 1.8±0.19 ml. When using the ointment form of levoxicol, the amount of displaced liquid when carrageenan was administered, starting from 3 hours, was 1.57±0.16 ml (p=0.013).

CONCLUSION: In vitro experiments have shown that the ointment form of levoxicol has a longer osmotic activity; experimental data in vivo indicated that the use of the developed ointment form of levoxicol, in contrast to the ointment form of levomekol, has a positive effect on the course of inflammatory processes in soft tissues in the first 2–3 hours by reducing the volume of displaced fluid.

Keywords

inflammation / osmotic activity / ointment form / carrageenan / edema

References

[1] Revishvili ASh, Sazhin VP, Olovyanniy VE, Zakharova MA. Current trends in emergency abdominal surgery in the Russian Federation. Pirogov journal of surgery. 2020;(7):6–11. (In Russ.) doi: 10.17116/hirurgia20200716

[2] Ревишвили А.Ш., Сажин В.П., Оловянный В.Е., Захарова М.А. Современные тенденции в неотложной абдоминальной хирургии в Российской Федерации // Хирургия. Журнал им. Н.И. Пирогова. 2020. № 7. С. 6–11. doi: 10.17116/hirurgia20200716

[3] Andreev AA, Glukhov AA, Ostroushko AP, Karapitian AR, Chuyan AO. The influence of acidity on the dynamics of reparative processes in soft tissues. Bulletin of experimental and clinical surgery. 2017;(10):64–71. (In Russ.) doi: 10.18499/2070-478X-2017-10-1-64-71

[4] Андреев А.А., Глухов А.А., Остроушко А.П., и др. Влияние кислотности на динамику репаративных процессов в мягких тканях // Вестник экспериментальной и клинической хирургии. 2017. № 10. С. 64–71. doi: 10.18499/2070-478X-2017-10-1-64-71

[5] Gostishchev VK, Gorbacheva IV. The possibility of using bacteriophages in the complex treatment and prevention of infections associated with the provision of medical care in patients with abdominal infection. Infektsii v khirurgii. 2018;16(1–2):30. (In Russ.) EDN: YQHFJR

[6] Гостищев В.К., Горбачева И.В. Возможность использования бактериофагов в комплексном лечении и профилактике инфекций, связанных с оказанием медицинской помощи, у больных с абдоминальной инфекцией // Инфекции в хирургии. 2018. Т. 16, № 1–2. С. 30. EDN: YQHFJR

[7] Chekmareva IA, Blatun LA, Terekhova RP, Zakharova OA, Kochergina EV, Agafonov VA. Morphological and functional aspects of wound regeneration in the treatment by iodine-containing ointments. Pirogov journal of surgery. 2014;1:54–58. (In Russ.) EDN: OFHBDF

[8] Чекмарева И.А., Блатун Л.А., Терехова Р.П., и др. Морфофункциональные аспекты регенерации ран при лечении йодсодержащими мазями // Хирургия. 2014. № 1. С. 54–58. EDN: OFHBDF

[9] Friedman NP, Styles K, Gray AM. Compliance with surgical antibiotic prophylaxis at an Australian teaching hospital. Am J Infect Control. 2013;41(1):71–74. doi: 10.1016/j.ajic.2012.02.012

[10] Friedman N.P., Styles K., Gray A.M. Compliance with surgical antibiotic prophylaxis at an Australian teaching hospital // Am J Infect Control. 2013. Vol. 41, N. 1. P. 71–74. doi: 10.1016/j.ajic.2012.02.012

[11] Leaper D, Ousey K. Evidence update on prevention of surgical siteinfection. Curr Opin Infect Dis. 2015;2(28):158–163. doi: 10.1097/QCO.0000000000000144

[12] Leaper D., Ousey K. Evidence update on prevention of surgical siteinfection // Curr Opin Infect Dis. 2015. Vol. 2, N. 28. P. 158–163. doi: 10.1097/QCO.0000000000000144

[13] Mashkovskii MD. Lekarstvennye sredstva. Posobie dlya vrachei. 15-e izd., pererab., ispr. i dop. (Medicines. A manual for doctors. 15th ed., reprint, corr. and add.) Moscow: Novaya volna; 2005. 1200 р. (In Russ.)

[14] Машковский М.Д. Лекарственные средства. Пособие для врачей. 15-е изд., перераб., испр. и доп. Москва: Новая волна, 2005. 1200 с.

[15] Dobrokvashin SV, Izmailov AG, Shakirova DH, Vasilkin DA. Primenenie preparata ksimedon v khirurgicheskoi praktike. Prakticheskie rekomendatsii. (Use of the drug xymedon in surgical practice. Practical recommendations.) Kazan: Tatkhimfarmparaty; 2017. 47 р. (In Russ.)

[16] Доброквашин С.В., Измайлов А.Г., Шакирова Д.Х., Василькин Д.А. Применение препарата ксимедон в хирургической практике. Практические рекомендации Казань: Татхимфармпрепараты, 2017. 47 с.

[17] Struchkov AA, Sokolov RA, Gordinskaya IA, Melnikova NB, Pogodin IE. Antimicrobial and reparative capabilities of a gel containing pyrimidine derivatives, sodium succinate and antibacterial agents in the local treatment of burn wounds. Bioradikaly i antioksidanty. 2018;5(1):47–56. (In Russ.) EDN: YTXTOE

[18] Стручков А.А., Соколов Р.А., Гординская И.А., и др. Противомикробные и репаративные возможности геля, содержащего пиримидиновые производные, натрия сукцинат и антибактериальные средства, при местном лечении ожоговых ран // Биорадикалы и антиоксиданты. 2018. T. 5, № 1. С. 47–56. EDN: YTXTOE

[19] Reznik VS. Interaction of oxy- and mercaptopyrimidines with ethylene and propylene chlorohydrins. Izvestiya AN SSSR. Seriya khimicheskaya. 1966;(91):13. (In Russ.)

[20] Резник В.С. Взаимодействие окси- и меркаптопиримидинов с этилен- и пропиленхлоргидринами // Известия АН СССР. Серия химическая. 1966. № 91. С. 13.

[21] Beschastnov VV, Izmailov SG, Botyakov AA, Zharinov AYu, Panteleev DA, Melnikova NB. Antioxidant activity of pyrimidine derivatives in the local treatment of purulent wounds of soft tissues (in experiment). Modern technologies in medicine. 2011;3:21–26. (In Russ.) EDN: OGHRHD

[22] Бесчастнов В.В., Измайлов С.Г., Ботяков А.А., и др. Антиоксидантная активность пиримидиновых производных при местном лечении гнойных ран мягких тканей (в эксперименте) // Современные технологии в медицине. 2011. № 3. С. 21–26. EDN: OGHRHD

[23] Parshikov VV, Loginov VI, Baburin AB, Kasimov RR. 50-year's path of development of postoperative wound infectious complications prophylaxis. Bashkortostan Medical Newsletter. 2017;12(1):82–93. (In Russ.) EDN: YFUHPD

[24] Паршиков В.В., Логинов В.И., Бабурин А.Б., Касимов Р.Р. Полувековой путь развития профилактики инфекционных осложнений в послеоперационных ранах (обзор литературы) // Медицинский вестник Башкортостана. 2017. Т. 12, № 1. С. 82–93. EDN: YFUHPD

[25] Izmailov SG, Lukoianychev EE, Leontev AE, Bodrov AA, Rotkov AI, Koloshein NA. Prophylactic “xymedon” in abdominal surgery. Bulletin of Experimental and Clinical Surgery. 2021;14(2):152–160. (In Russ.) doi: 10.18499/2070-478X-2021-14-2-152-160

[26] Измайлов С.Г., Лукоянычев Е.Е., Леонтьев А.Е., и др. Профилактическое применение кисмедона в абдоминальной хирургии // Вестник экспериментальной и клинической хирургии. 2021. Т. 14, № 2. С. 152–160. doi: 10.18499/2070-478X-2021-14-2-152-160

[27] Izmaylov SG, Beschastnov VV, Zharinov AYu, Botyakov AA, Ryabkov MG, Reznik VS, Izmailov AG, Averyanov MYu, Kazarina NV. Composition for septic wound repair. Patent RUS No. 2348396. Byul. No. 7 dated 10.03.2009. (In Russ.) EDN: LINDMQ

[28] Измайлов С.Г., Бесчастнов В.В., Жаринов А.Ю., и др. Композиция для лечения гнойных ран. Патент РФ на изобретение №2348396. Бюл. №7 от 10.03.2009. EDN: LINDMQ

RIGHTS & PERMISSIONS

Eco-Vector