It is known that fulvic acids (FA) have a whole complex of therapeutic properties, but their widespread introduction into medical practice is limited by the dependence of the properties of the final product on the source of their extraction. In this regard, research aimed at developing experimental approaches for the production of synthetic substances that are similar in structure, physical, chemical and therapeutic properties to natural FA, but characterized by standardized and controlled parameters, is of interest. The purpose of the work was to develop a method of obtaining synthetic FA using as a precursor ellagitannins and lignin extracted from pomegranate peels and comprehensive study of their properties. As a result of the experiment and the analysis of the results it was found that the elagotanins and lignin contained in the peel of pomegranate can be used as a precursor to obtain synthetic FA. Comparative analysis of the elemental composition and spectral characteristics of synthetic FA with the literature data for natural FA allowed to ascertain the uniformity of their chemical structure. X-ray diffraction analysis of synthetic FA indicates their amorphous nature, which is typical of natural FA as well. The content of basic acid groups in the structure of synthetic FAs and their recovery capacity are calculated. In particular, the content of carboxyl groups is 2.7 ± 0.2 mmol/g, and the phenolic groups - 6.0 ± 0.1 mmol/g; the recovery capacity is 5.2 ± 0.3 mmol/g. The SEM images of the dried synthetic FA preparations show the uniformity of the powder particles obtained. However, unlike natural FA, synthetic analogues obtained by the developed method are characterized by controlled and reproducible properties, which greatly expands their use in medicine.
2. Orlov D.S. Humic acids of soils and the general theory of humification. - M.: Moscow State University, 1990, 325 p. [in Russian].
3. Van Rensburg C. E. J. The Antiinflammatory Properties of Humic Substances: A Mini Review // Phytother. Res. 2015. 1-6.
4. Motojima H. O., Villareal M., Han J., Isoda H. Microarray analysis of immediate-type allergy in KU812 cells in response to fulvic acid. Cytotechnology. 2011. 63(2): 181–90.
5. Tachibana Y., Hiribe S., Tawa R. Studies of antioxidative activity of humic substances in peat. Trace Nutrients Res. 2004. 23: 104–108.
6. Van Rensburg C. E. J., van Straten A, Dekker J. An in vitro investigation of the antimicrobialactivity of oxifulvic acid. J. Antimicrob. Chemother. 2000. 46: 853–854.
7. Van Rensburg C. E. J., Malfeld S. C. K., Dekker J. Topical application of oxifulvic acid suppresses the cutaneous immune response in mice. Drug Dev. Res. 2001. 53: 29–32.
8. Kodama H. Antitumor effect of humus extract on murine transplantable L1210 Leukemia. J. Vet. Med. Sci. 2007. 69(10): 1069–71.
9. Sherry L., Jose A., Murray C., Williams C., Jones B., Millington O., Bagg J., Ramage G. Carbohydrate Derived Fulvic Acid: An in vitro Investigation of a Novel Membrane Active Antiseptic Agent Against Candida albicans Bio-films. Front Microbiol. 2012. 3: 116.
10. Gandy J.J., Snyman J.R., van Rensburg C.E. Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema. Clin. Cosmet. Investig Dermatol. 2011. 4: 145-8.
11. Ghosal S., Singh S.K., Kumar Y. Antiulcerogenic of fulvic acids and 4-methoxy-6-zarbomethoxybiphenyl isolated from shilaji. Phytotherapy Research. 1988. 2(4): 187–191.
12. Carrasco-Gallardo C., Guzmán L., Maccioni R.B. Shilajit: a natural phytocomplex with potential procognitive activity. Int. J. Alzheimers Dis. 2012. 674142.
13. Winkler J., Ghosh S. Therapeutic Potential of Fulvic Acid in Chronic Inflammatory Diseases and Diabetes. J. Diabetes Res. 2018. 7.
14. Morales O.Y., Navarrete J.M., Gracia I., Macías L., Rivera M., Sánchez F. Fulvic Acids and Viral Infections. Open. Conf. Proc. J. 2012. 3: 24-29.
15. Gandy J.J., Meeding J.P., Snyman J.R., van Rensburg C.E. Phase 1 clinical study of the acute and subacute safety and proof-of-concept efficacy of carbohydrate-derived fulvic acid. Clin. Pharmacol. 2012. 4: 7-11.
16. Cataldo F. On the structure of macromolecules obtained by oxidative polymerization of polyhydroxyphenols and quinones. Polym. Int. 1998. 46: 263.
17. Jung A. V., Frochot C., Parant S., Lartiges B. S., Selve C., Viriot M. L., Bersillon J. L. Synthesis of amino-phenolic humic-like substances and comparison with natural aquatic humic acids: a multi-analytical techniques approach. Org. Geochem. 2005. 36: 1252.
18. Sławińska D., Polewski K., Rolewski P., Sławiński J. Synthesis and properties of model humic substances derived from gallic acid. Int. Agrophys. 2007. 21: 199.
19. Pat. 5945446 United States, Int.Cl6 A 61 K 31/35; A 01 N 35/78. Process for Preparing Synthetic Soil-Extract Materials and Medicaments Based Thereon / R. J. Laub; Laube Biochemicals. – N 08/798,329; filing 10.02.1997; publ. 31.08.99.
20. Litvin V.A., Minaev B.F., Baryshnikov G.V. Synthesis and properties of synthetic fulvic acid derived from hematoxylin. J. Mol. Struct. 2015. 1086: 25.
21. Litvin V. A., Galagan R. L., Minaev B. F. Synthesis and Properties of Synthetic Analogs of Natural Humic Acids Russian Journal of Applied Chemistry. 2012. 85 (2): 296.
22. Danchenko N. N. The functional composition of humic acids: determination and relationship with reactivity: diss. ... cand. chem. Scienc-es: 02.00.03, 11.00.11 / Danchenko Natalya Nikolaevna. M., 1997. 135. [in Russian].
23. Struyk Z., Sposito G. Redox properties of standard humic acids. Geoderma. 2001. 102: 329.
24. Taha M. A. Razek Impact of primary treated sewage water on the chemical composition of safflower oil as a potential candidate for bio-diesel production. IOSR J Environ Sci Toxicol Food Technol. 2013. 7 (1): 38-42.
25. Rowayshed G., Salama A., Abul-Fadl M., Akila-Hamza, S., Emad A. Mohamed Nutrition-al and Chemical Evaluation for Pomegranate (Punica granatum L.) Fruit Peel and Seeds Powders By Products. Middle East J. Appl. Sci. 2013. 3(4): 169-179.
26. Garcia-Villalba R., Espín J. C., Kroon P. A., Alasalvar C., Aaby K., Heinonen M., Voorspoels S., Tomas-Barberan F. A validated method for the characterization and quantification of extractable and non-extractable ellagitannins after acid hydrolysis in pomegranate fruits, juices, and extracts. Journal of Agricultural and Food Chemistry. 2015. 63(29): 6555.
27. Wu S., Tian L. Diverse Phytochemicals and Bioactivities in the Ancient Fruit and Modern Functional Food Pomegranate (Punica granatum). Molecules. 2017. 22(10): 473.
28. Yasoubi, Barzegarl M., Sahari M.A., Azizi M.H. Total phenolic contents and antioxidant activity of Pomegranate (Punica granatum L.) peel extracts. J. Agri. Sei. Technol. 2007. 9: 35.
29. Mavlyanov S.M., Ismailov A.I., Islambekov Sh. Yu. Plant tannins. Chemistry of nature com-pounds. 2001. 1: 36. [in Russian].
30. Mahboubi A., Asgarpanah J., Sadaghiyani P.N., Faizi M. Total phenolic and flavonoid content and antibacterial activity of Punica granatum L. var. pleniflora flowers (Golnar) against bacterial strains causing foodborne diseases. BMC complementary and alternative medicine. 2015. 15: 366.
31. Landete J.M. Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health Food Research International. 2011. 44: 1150.
32. Ahmed S.A., Abood N.H., Al-Janabi A.A. Antimicrobial effect of Pomegranate peels extract on some pathogenic microorganisms. Engg. Tech. J. 2013. 31(3): 1.
33. Pogosyan R.A., Nestorova O.V., Dobrokhotov D.A. Historical experience and the prospect of using pomegranate fruits in medicine and pharmacy (Punica granatum). Journal of scientific articles “Health and Education in the 21st Century”. 2016. 18 (5): 131.
34. Litvin V.A., Minaev B.F. Spectroscopy study of silver nanoparticles fabrication using synthetic humic substances and their antimicrobial activity. Spectrochim. Acta, Part A. 2013. 108: 115.
35. Akaighe N., MacCuspie R. I., Navarro D. A., Aga D. S., Banerjee S., Sohn M., Sharma V. K. Humic acid-induced silver nanoparticle formation under environmentally relevant conditions. Environ. Sci. Technol. 2011. 45, 9: 3895–3901.