Antarite - synergistic combination of «magaldrat + simethicone» with gastroprotective properties

Resume. TThe preparation "Antarite” is a combination of magaldrate (antacid of a new generation) with simethicone (antifoam component to reduce flatulence). The antacid effect of the drug develops quickly (1-2 minutes) and lasts for a long time (up to 3 hours). Magaldrat is antacid of multitarget effect, exhibiting a pronounced cytoprotective effect on the gastric mucosa. When the galdrate is dissolved in the hydrochloric acid of the stomach, the crystal structure of this substance causes the formation of tightly packed aluminum hydroxide particles. These particles envelop the area of ulceration, and the size of these particles (2 microns) is such that it facilitates the migration of epithelial cells and fibroblasts in the process of repair of the stomach wall. Additional curative effects of magaldrate are associated with the gradual secretion of magnesium and aluminum ions (hexa-aluminum), which help to maintain optimal concentrations of these ions. The biological effects of aluminum ions are accomplished by activating G-proteins and inhibiting adenylate cyclases. As a result, the metabolism of prostaglandins is modulated, the levels of the vasodilator of nitric oxide (NO) increase, and antihistamine effects are manifested - important components of the multitarget action of magaldrate.

антациды, G-белки, магалдрат, Антарейт, фармакокинетика, фармакодинамика, интеллектуальный анализ данных, antacids, G-proteins, magaldrat, Antarite, pharmacokinetics, pharmacodynamics, data mining

1. Patel AV, Santani DD, Goyal RK. Antiulcer activity and the mechanism of action of magaldrate in gastric ulceration models of rat. Indian J Physiol Pharmacol. 2000;44(3):350–354.

2. Cousar GD, Gadacz TR. Comparison of antacids on the binding of bile salts. Arch Surg. 1984; 119(9):1018–1020.

3. Arnold R, Garbe I, Koop H, et al. Effect of antacid and H2-receptor blocker treatment on gastric endocrine cells. Scand J Gastroenterol Suppl. 1984;101:31–37.

4. Громова О.А., Торшин И.Ю., Максимов В.А. Магалдрат как антацид с мульти-таргетным воздействием: клинико-фармакологическое эссе // Лечащий врач. – 2018. – № 2. 67 с. [Gromova OA, Torshin IYu, Maksimov VA. Magaldrat kak antatsid s mul'ti-targetnym vozdeistviem: kliniko-farmakologicheskoe esse. Lechashchii vrach. 2018;2(67):67. (In Russ).]

5. Peterson CL, Perry DL, Masood H, et al. Characterization of antacid compounds containing both aluminum and magnesium. I. Crystalline powders. Pharm Res. 1993;10(7):998–1004.

6. Winterberg B, Bertram H, Rolf N, et al. Differences in plasma and tissue aluminum concentrations due to different aluminum-containing drugs in patients with renal insufficiency and with normal renal function. J Trace Elem Electrolytes Health Dis. 1987;1(2):69–72.

7. Wilson GE Jr, Falzone CJ, Johnson R, Lee HK. Action of hydrochloric acid on aluminum hydroxide-magnesium hydroxide gels and magaldrate: 27Al NMR and pH-stat studies. J Pharm Sci. 1985;74(10):1075–1077.

8. Graf GA, Burns PD, Silvia WJ. Oxytocinand aluminium fluoride induced phospholipase C activity and prostaglandin F2 alpha secretion during the ovine luteolytic period. JReprodFertil. 1998;112(2):225–231.

9. Торшин И.Ю., Громова О.А. Экспертный анализ данных в молекулярной фармакологии. МЦНМО; 2012. [Torshin IYu,Gromova OA. Expert Data Analysis in Molecular Pharmacology. MTsNMO; 2012. (In Russ).]

10. Wessel K, Resch K, Kaever V. Aluminium fluoride enhances phospholipase A2 activity and eicosanoid synthesis in macrophages. Eicosanoids. 1989;2(4):223–227.

11. Ong J, Kerr DI. Interactions of N-ethylmaleimide and aluminium fluoride with GABAB receptor function in rat neocortical slices. Eur J Pharmacol. 1995;287(2):197–200.

12. Liu P, Wen M, Hayashi J. Guanine nucleotide-binding protein stimulates arachidonic acid metabolism in TEA3A1 thymic epithelial cells by stimulating release and inhibiting incorporation of arachidonic acid. Biochem Mol Biol Int. 1993;31(4):613–625.

13. Rawlinson SC, Wheeler-Jones CP, Lanyon LE. Arachidonic acid for loading induced prostacyclin and prostaglandin E(2) release from osteoblasts and osteocytes is derived from the activities of different forms of phospholipase A(2). Bone. 2000;27(2):241–247.

14. Wittenberg JM, Wittenberg RH, Osborn JF. Prostaglandin release from rat femurs after implantation of hydroxylapatite and aluminium oxide ceramics. Prostaglandins Leukot Essent Fatty Acids. 1995;53(6):413–417.

15. Berstad K, Vergin H, Postius S, et al. Gastric prostaglandin E2 release induced by aluminium hydroxide and aluminium hydroxide-containing antacids in rats. Effect of low doses and citric acid. Scand J Gastroenterol. 1987;22(7):884–888.

16. Konturek SJ, Brzozowski T, Majka J, et al. Nitric oxide in gastroprotection by aluminium-containing antacids. Eur J Pharmacol. 1992;229(2-3):155–162.

17. Yang L, Tian D, Todd CD, et al. Comparative proteome analyses reveal that nitric oxide is an important signal molecule in the response of rice to aluminum toxicity. J Proteome Res. 2013;12(3):1316–1330. DOI: 10.1021/pr300971n

18. Evora PR, Pearson PJ, Schaff HV. Impaired endothelium-dependent relaxation after coronary reperfusion injury: evidence for G-protein dysfunction. Ann Thorac Surg. 1994;57(6):1550–1556.

19. Kuchan MJ, Jo H, Frangos JA. Role of G proteins in shear stress-mediated nitric oxide production by endothelial cells. Am J Physiol. 1994 Sep;267(3):753–758.

20. Stevanovic ID, Jovanovic MD, Colic M, et al. Cytochrome c oxidase activity and nitric oxide synthase in the rat brain following aluminium intracerebral application. Folia Neuropathol. 2013;51(2):140–146.

21. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev. 1999 Nov 15;13(22):2905–2927.

22. Parkinson LG, Giles NL, Adcroft KF, et al. The potential of nanoporous anodic aluminium oxide membranes to influence skin wound repair. Tissue Eng Part A. 2009;15(12):3753–3763. DOI: 10.1089/ten.tea.2008.0594

23. Guterman LR, Falzone J, Wilson GE Jr. Action of hydrochloric acid on aluminum hydroxide-magnesium hydroxide gels and magaldrate: quasielastic light scattering studies. J Pharm Sci. 1986;75(5):502–505.

24. Swart AC, Klaassen BH, Bloys-van Treslong-de, Hemker HC. The adsorption of blood coagulation factors II, VII, IX and X from human plasma to aluminium hydroxide. Thromb Diath Haemorrh. 1972;27(3):490–501.

25. Громова О.А., Торшин И.Ю., Рудаков К.В., и др. Систематический анализ магнийзависимых митохондриальных белков // Кардиология. – 2014. – Т. 54. – № 9. – С.86–92. [Gromova OA, Torshin IYu, Rudakov KV, et al. Systematic Analysis of Magnesium Dependent Mitochondrial Proteins. Kardiologiia. 2014;54(9):86–92. (In Russ).] DOI: 10.18565/cardio.2014.9.86-92

26. Belin RJ, He K. Magnesium physiology and pathogenic mechanisms that contribute to the development of the metabolic syndrome. MagnesRes. 2007;20(2):107–129.

27. Эффективность магнийсодержащего препарата "Поликатан" в терапии гнойных ран Спасов А.А., Фомичев Е.В., Гусева Т.Н., и др. Бюллетень экспериментальной биологии и медицины. – 2001. – Т. 131. – № 2. – С. 163–166. [SpasovAA, FomichevEV, GusevaTN, etal. Efficiency of magnesium-containing preparation polykatan in therapy of purulent wounds. Bull Exp Biol Med. 2001;131(2):132–135. (In Russ).] DOI: 10.1023/a:1017531609786

28. Heidarianpour A, Sadeghian E, Gorzi A, Nazem F. The influence of oral magnesium sulfate on skin microvasculature blood flow in diabetic rats. Biol Trace Elem Res. 2011;143(1):344–350. DOI: 10.1007/s12011-010-8842-7

29. Yue H, Lee JD, Shimizu H, et al. Effects of magnesium on the production of extracellular matrix metalloproteinases in cultured rat vascular smooth muscle cells. Atherosclerosis. 2003;166(2):271–277. DOI: 10.1016/s0021-9150(02)00390-8

30. Юдина Н.В., Торшин И.Ю., Громова О.А., и др. Обеспеченность ионами калия и магния – фундаментальное условие для поддержания нормального артериального давления // Кардиология. – 2016. – Т. 56. – № 10. – С. 80–89. [Yudina NV, Torshin IYu, Gromova OA, et al. Availability of Potassium and Magnesium Ions Is a Fundamental Condition for Maintenance of Normal Arterial Pressure. Kardiologiia. 2016;56(10):80–89. (In Russ).] DOI: 10.18565/cardio.2016.10.80-89

31. Громова О.А., Торшин И.Ю., Юдина Н.В., и др. Дефицит магния и нарушения регуляции тонуса сосудов // Кардиология. – 2014. – Т. 54. – № 7. – С. 66–72. [Gromova OA, Torshin IYu, Yudina NV. Magnesium Deficiency and Dysregulation of Vascular Tone. Kardiologiia. 2014;54(7):66–72. (In Russ).] DOI: 10.18565/cardio.2014.7.66-72

32. Громова О.А., Торшин И.Ю. Магний и «болезни цивилизации». – М.: ГЭОТАР-Медиа; 2018. [Gromova OA, Torshin IYu. Magnii i «bolezni tsivilizatsii». Moscow: GEOTAR-Media; 2018/ (In Russ).].

33. Cox RD, Osgood KA. Evaluation of intravenous magnesium sulfate for the treatment of hydrofluoric acid burns. J Toxicol Clin Toxicol. 1994;32(2):123–136.

34. Adewoye EO, Salami AT. Anti-ulcerogenic mechanism of magnesium in indomethacin induced gastric ulcer in rats. Niger J Physiol Sci. 2013;28(2):193–199.

35. Sasaki Y, Sathi GA, Yamamoto O. Wound healing effect of bioactive ion released from Mg-smectite. Mater Sci Eng C Mater Biol Appl. 2017;77:52–57. DOI: 10.1016/j.msec.2017.03.236

36. Вологжанина Л.Г., Владимирский Е.В. Эффективность применения питьевой сульфатной магниево-кальциевой минеральной воды в комплексном лечении больных язвенной болезнью двенадцатиперстной кишки, сочетающейся с гастроэзофагеальной рефлюксной болезнью // Вопросы курортологии, физиотерапии и лечебной физической культуры. – 2005. – № 6. – С. 17–19 [VologzhaninaLG, VladimirskiiEV. Efficacy of the drinking magnesium-calcium sulfate mineral water in the combined treatment of duodenal ulcer comorbid with gastroesophageal reflux. Vopr Kurortol Fizioter Lech Fiz Kult. 2005;(6): 17–19. (In Russ).]

37. Razzaghi R, Pidar F, Momen-Heravi M, et al. Magnesium Supplementation and the Effects on Wound Healing and Metabolic Status in Patients with Diabetic Foot Ulcer: a Randomized, Double-Blind, PlaceboControlled Trial. Biol Trace Elem Res. 2018;181(2):207–215. DOI: 10.1007/s12011-017-1056-5

38. Suzuki N, Hajicek N, Kozasa T. Regulation and physiological functions of G12/13-mediated signaling pathways. Neurosignals. 2009;17(1):55–70. DOI: 10.1159/000186690