MXPA99007281A - Process for preparing synthetic soil-extract materials and medicaments based thereon - Google Patents

Abstract

Phenolic polymers are prepared by dissolving one or more organic phenols along with sodium periodate in aqueous base at pH 8-11, and allowing the mixtures to stand between 35 and 80°C for a period of 30 minutes to 100 hours. One or more inorganic compounds or salts is added and the solution is allowed to stand at room temperature between 2 and 48 hours. Salt molecules as well as starting compounds and other low molecular-weight materials below about 500 to about 10,000 daltons are removed from the product solutions. Purified phenolic polymers are prepared in concentrated aqueous solution or in dried powder form in a final step if necessary. The resultant phenolic polymers exhibit physicochemical properties strongly resembling those of typical commercially-available natural soil extracts. The materials are active anti-viral and anti-microbial agents, and are effective in anti-viral amounts in blood product compositions, in methods for reducing or eliminating virus in blood products and in anti-viral and anti-microbial compositions for treating or preventing human or animal viral or microbial diseases.

Description

PROCESS FOR PREPARING SYNTHETIC MATERIALS OF SOIL EXTRACT AND MEDICINES BASED ON THEM Field of the Invention This invention relates to synthetic substances of soil extract comprised of phenolic polymers, to processes for the preparation thereof, to processes for purification and isolation as aqueous solutions or dehydrated powders of synthetic materials, to compositions and methods for employing these synthetic phenolic polymers to reduce or eliminate viral activity in blood products, antiviral compositions for treating or preventing viral diseases of humans or animals and antimicrobial compositions for treating or preventing microbial diseases of humans or animals. BACKGROUND OF THE INVENTION Soil extract materials, particularly classes of substances collectively known as "humus", "humic", "humic acid (s)" or "humates", have for years been widely used in various applications, as reviewed by FJ Stevenson, Humus Chemistry. Genesis Composition Reactions; New York: Wiley, 1964; and, more recently, by A. Píccolo, Humic Substances in Terrestrial Ecosystems; New York: Elsevier, 1996. Natural and synthetic soil extracts have already been widely used in the horticultural and related industries, particularly as soil reinforcement agents, as well as soil repair agents. In addition, natural and synthetic soil extracts have been used as additives in organic gardening and garden design; and in freshwater aquariums. Some medicinal benefits have also been declared for both synthetic and natural soil extract substances. R. H. Faust, in a document presented at the Conference of the International Federation of Organic Agriculture Movements; Copenhagen, Denmark: October 1996; P2, 20, has documented the benefits of humatos in agriculture. In general, it has been found that humic materials can stimulate the growth of plants, including the production of the crop, around 10-30%.

The extracts of soil and humic acid in particular, chelate a variety of metals. As a result, humic materials have been used in soil repair to eliminate heavy metal contamination, as reported by M. A. Rashid, Soil Sci. 1971, 111, 298-306. Humic acid has also been used to improve the removal of aromatic hydrocarbons from aquifers contaminated with petroleum products: H., S. Lesage, L. Durham and K. Novakowski, in Proceedings of the Fourth Annual Symposium on Groundwater and Soil Remediation; Calgary, Alberta: September 21-23, 1994; 635-646; S. Lesage, H. Xu, K. S. Novakowski, S. Brown and L. Durham, in Proceedings of the Fifth Annual Symposium on Groundwater and Soil Remediation; Toronto, Ontario: 2-6 October 1995. Humatos materials have been used as additives for poultry feed. The addition of humate materials to forage of young chickens increases the volume of the crop on average 5-7% and also provides a gain of 3-5% in the safety of poultry: LM Stepchenko, LV Zhorina and LV Kravtsova , Biol. Nauki 1991, 10, 90-95. TA Huck, N. Porter and ME Bushell, J. "Gen. Microbiol., 1991, 137 (10), 2321-2329, have reported that soil isolates are additives of effective means for the production of antibiotics and that the The stimulation of microbial growth can be very large depending on the species, the culture medium and the environment.The use of selected lots of soil lignite humates as culture media to isolate thermophilic extracts of the Campilobacter species has also been documented by K. Weinrich, K. Winkler and E. Heberer, DTW Dtsch, Tierarztl Wochenschr, 1990, 57 (12), 511-515, In addition, B. Grunda, Zentralbl, Bakteriol, Parasi tenkd, Infektionskr, Hyg., 225 (6), 584-593, has described the effects of humic acid on the counting of soil microorganisms in the crop. Humatos have long been used as primitive remedies for a wide variety of diseases (F. K. Achard, Crells Chem. Ann. 1786, 11, 391-403), as detailed by T. D. Lotosh, Biol. Nauki 1991, 10, 99-103. The humic acids isolated from the peat showed considerable efficacy for adhesions when tested in female rats having standardized lesions in both uterine horns and the peritoneum of the anterior abdominal wall: M. Mesrogli, DH Maas, B. Mauss, S. Plogmann, W. Ziechmann and J. Schneider, Zentralbl. Gynakol. 1991, 113 (10), 583-590. The ability of natural humic acid to affect anaphylactic sensitization and mast cell secretory function has been established by J7 Wyczolkowska, T. Michon, Z. Slusarczyk, B. Kolago and C. Maslinski, Acta Pol. Pharm. 1993, 50 (6), 475-480. Humic substances in doses of 20 and 50 milligrams per kilogram of body weight reduced the release of histamine from mouse peripheral mastocytes stimulated with anti-IgE or concanavalin A in vitro. It is known that humic substances, including peat and sodium humates, have anti-inflammatory properties: M.

Kuhnert, V. Fuchs and S. Golbs, Arch. Exp. Veterinarmed. 1982, 36 (2), 169-111; S. B. Ye, J. Y. Chen and Z. X. Zeng, Ssu Chuan I Hsueh Yuan Hsueh Pao 1985, 16 (2), 127-129. The inflammatory states of the cervix, especially cervical erosion (generally known as cervicitis), can be treated with humic preparations: J. Woyton, M. Gabrys, T. Bielanow, M. Zimmer, J. Sokalski, R. Geneja and M. Zborowski , Arch. Immunol. Ther. Exp. (Warsz) 1993, 41 (1), 99-103. It has been known that humic substances have antimicrobial properties. Species for which natural, as well as synthetic, humic substances have been shown to be inhibitory include C. albicans, Ent. cloacae, Prot. vulgaris, Ps. aeruginosa, S. typhimurium, St. aureus, St. epidermidis, Str. pyogenes (R. Ansorh and Rochus, Arzneimi ttelforschung 1978, 28 (12), 2195-2198; E. coli and Str. faecalis were not affected) and Str. mutans (sobrinus) (Y. Nakamura, H. Kuwashima, S. Aoki and T. Masuhara, Shika Kiso Igakkai Zasshi 1989, 31 (3), 329-332. In general terms, concentrations in the range of 50-2000 parts per million (ppm) are generally effective, but not cytotoxic: KD Thiel, B. Helbig, R. Klocking, P. Wutzler, M. Sprossig and H. Schweizer, Pharmazie 1981, 36 (1), 50-53. It has been known for a long time that humic substances have antiviral properties (H. Schultz, Dtsch, Tierarztl, Wochenschr, 1962, 69, 613, 1965, 72 (13), 294-297; R. Klocking and M. Sprossig, Experientia 1972, 28 (5), 607-608), particularly retroviruses (G. Sydow, V. Wunderlich, R. Klocking and B. Helbig, Pharmazie 1986, 41 (12), 865- 868). Viral pathogens for which soil extract materials have been shown to be effective include in particular Coxsackie A9 virus (Griggs-Baylor) (R. Klocking and M. Sprossig, Experientia 1972, 28 (5), 607-608), herpes simplex virus type 1 (BT Rouse (Ed.), Herpes Simplex Virus, Berlin: Springer-Verlag, 1992, R. Klocking, KD Thiel, P. Wutzler, B. Helbig and P. Drabke, Pharmazie 1978, 33 ( 8), 539, F. Schiller, R. Klocking, P. Wutzler and I. Farber, Dermatol, Monatsschr, 1979, 165 (1), 505-509, B. Helbig, A. Sauerbrei, R. Klocking, P. utzler, N. Wicht, U. Wiedemann and G. Herrmann, J. Med. Vi.U. 1987, 23 (3), 303-309, R. Klocking and B. Helbig, in Humic Substances in the Aquatic and Terrestrial Environment ( Humic Substances in the Aquatic and Terrestrial Environment), Berlin: Springer-Verlag, 1991; 407-412); and type 2 (anonymous ZentralJbl, Bakteriol [Orig.A] 1976, 234 (2), 159-169; KD Thiel, R. Klocking, H. Schweizer and M. Sprossig, Zentralbl. Bakteriol [Orig. A] 1977, 235 (3), 304-321; KD Thiel, B. Helbig, R. Klocking, P. Wutzler, M. Sprossig and H. Schweizer, Pharmazie 1981, 36"(1), 50-53; KD Thiel, B. Helbig , M. Sprossig, R. Klocking and P. Wutzler, Acta Virol. 1983, 27 (3), 200-208, KD Thiel, P.Wutzler, B. Helbig, R. Klocking, M. Sprossig and H. Schweizer, Pharmazie 1984, 35 (11), 7891-782), human immunodeficiency virus (HIV) (M. Cushman, P. Wang, SH Chang, C. Wild, E. De Clercq, D. Schols, ME Goldman and JA Bowen , J. Med. Chem. 1991, 34 (1), 329-337, M. Cushman, S. Kanamathareddy, E. De Clercq, D. Schols, ME Goldman and JA Bowen, J. Med. Chem. 1991, 34 (1), 337-342; D. Schols, P. Wutzler, R. Klocking, B. Helbig and E. De Clercq, J. Acquir. I mune Defic. Syndr. 1991, 4 (7), 677-685 S. Loya, R. Tal, A. Hizi, S. Issacs, Y. Kashman and Y. Loya, J7 IVat. Prod. 1993, 55 (12 ), 2120-2125; J. Schneider, R. Weis, C. Manner, B. Kary, A. Werner, B. J7 Seubert and U. N. Riede, Virology 1996, 228 (2), 389-395; influenza virus type A (Krasnodar / l0l / 59 / H2N2) (R. Mentel, B. Helbig, R. Klocking, L. Dohner and M. Sprossig, Biomed, Biochim, Act 1983, 42 (10), 1353-1356 ); and Type B (J. Hils, A. May, M. Sperber, R. Klocking, B. Helbig and M. Sprossig, Biomed, Biochim, Acta 1986, 45 (9), 1173-1179) as well as other infectious agents of the respiratory system (A. Jankowski, B. Nienartowicz, B. Polanska and A. Lewandowicz-Uszynska, Arch. I munol. Ther. Exp. (Warsz) 1993, 41 (1), 95-97). The mechanism by means of which humic substances inhibit the cytopathicity of a quantity of virus has been studied with certdetails. It is believed that the materials prevent viral replication by absorbing the viral envelope protein (gpl20SU in the case of HIV), thus blocking the absorption of viral particles to cell surfaces: KD Thiel, R. Klocking, H. Schweizer and M. Sprossig, Zentralbl. Bakteriol. [Orig. A] 1977, 235 (3), 304-321; D. Schols, P. Wutzler, R. Klocking, B. Helbig and E. De Clercq, J. Acquir. Immune Def. Syndr. 1991, 4 (7), 677-685; Anonymous, Fortschr. Med. 1995, 113 (7), 10; J. Schneider, R. Weis, C. Manner, B. Kary, A. Werner, B. J. Seubert and U. N. Riede, Virology 1996, 228 (2), 389-395. The extracellular interception of pathogens by chemical agents that bind to them is a well-known immunological defense procedure (DM Shankel, S. Kuo, C. Haines and LA Mitscher, in Antimutagenesis and Anticarcinogenesis Mechanisms III, G. Bronzetti, H. Hayatsu , S. De Flora, MD Waters and DM Shankel (Eds.), New York: Plenum, 1993; 65-74). These materials could be referred to as "depathogens", following the terminology proposed by T. Kada and K. Shimoi, Bioessays 1987, 7, 113-116, with respect to "demutagen". It has been reported that heat treatment of humic acids at 120 degrees Celsius for 15 minutes does not alter its inhibitory effect on mutagens: T. Sato, Y. Ose and H. Nagase, Mutat. Res. 1986, 152 (2), 173-178; T. Sato, Y. Ose, H. Nagase and K. Hayase, Sci. Total Environ. 1987, 52 (4), 305-310). That is, the humic acids can be sterilized by autoclaving. A direct comparison of enzymatic humic acid with humic acid synthesized nonenzymatic has shown that the latter is almost a factor of ten more effective than the first for the treatment of herpes types 1 and 2: KD Thiel, P. Wutzler, B. Helbig , R. Klocking, M. Sprossig and H. Schweizer, Pharmazie 1984, 35 (11), 781-782. Bovine calcium hydroxyapatite implanted is highly osteoconductive and serves the host tissue as a "guideline" for the deposition of newly developing bone tissue. However, while it is well tolerated, it is only resorbed very slowly. The impregnation of bovine hydroxyapatite with synthetic humic acid measurably stimulates the resorption process. There is an extensive covalent, as well as a hydrogen bond of humic substances to collagen fibers (also with undoubted degradation), as determined by the X-ray diffraction analysis: UN Riede, I. Jonas, B. Kirn, UH Usener , W. Kreutz and W. Schlickewey, Arch. Orthop. Trauma Surg. 1992, 111 (5), 259-264. Therefore the strength of the tendon is increased as much as 75 percent. It has been found that natural as well as synthetic humic acids stimulate the phagocytic and bactericidal activity of granulocytes in humans at dose levels of 100-300 milligrams per day for a trial period of 14 days: UN Riede, G. Zeck-Kapp , N. Freudenberg, HU Keller and B. Seubert, Virchows Arch. B Cell Pathol. Incl. Mol.

Pathol. 1991, 50 (1), 27-34; M. Kowalska, A. Denys and J. Bialek, Acta Pol. Pharm. 1993, 50 (4-5), 393-395. Of additional interest is the finding that dose levels of 600 milligrams per day caused only a temporary and insignificant increase in phagocytic and bactericidal properties of granulocytes. The influence of natural as well as synthetic humic acids on hemostasis has been studied: H. P. Klocking, Arch. Toxi col. Suppl. 1991, 14, 166-169; W. Buczko, B. Malinowska, M. H. Pietraszek, D. Pawlak and E. Chabielska, Acta Pol. Pharm. 1993, 50 (6), 507-511. It was found that humic acid at dose levels of 100-300 milligrams per kilogram of body weight had no effect on the bleeding time, coagulation time, thrombin time, prothrombin time, kaolin-cephalin time, Euglobulin lysis, fibrinogen concentration, platelet count, or the addition of ADP-induced platelets. It has been found that several synthetic humic acids completely inhibit the activity of purified lipoxygenase of rabbit reticulocytes, considering that the prostaglandin H synthase of the sheep vesicular gland is only barely inhibited: C. Schewe, R. Klocking, B. Helbig and T. Schewe, Biomed. Biochim. Acta 1991, 50 (3), 299-305. The most effective humic acids were those derived from caffeic acid, 2,5-dihydroxytoluene and 3,4-dihydroxytoluene. The effect of natural humic acid on the regenerative response of liver tissue in rats subjected to two thirds of hepatectomy has been examined. It was thought that the results were double by nature. First, the short-term application of humic acid in a dose of 20 milligrams per kilogram of body weight per day inhibited the activity of ornithine decarboxylase, as well as caused a decrease in the formation of spermidine and DNA and RNA, giving as Result a general decrease in the restitution of the liver. In contrast, the long-term application of humic acid caused the stimulation of ornithine decarboxylase, an increase in spermidine and histamine, as well as RNA and DNA levels and in the overall volume of the liver. The effects could be due at least in part to the inhibition of humic acid from polyamine biosynthesis: C. Maslinksi, W. A. Fogel and W. Andrzejewski, Acta Pol. Pharm. 1993, 50 (4-5), 413-416. It has been shown that humic and fulvic acids extracted from peat stimulate respiration in the liver mitochondria of rats when they are present at concentrations of 40-360 micrograms per milliliter. Humic substances in concentrations of 40-400 micrograms per milliliter also increased the efficiency of oxidative phosphorylation in the mitochondria in vitro, particularly after contact periods of more than one hour: S. A. Visser, Sci. Total Environ. 1987, 52 (4), 347-354. Natural, synthetic and commercial humic acids have the ability to inhibit human plasmin activity: F. J. Lu and Y. S. Lee, Sci. Total Environ. 1992, 224 (4), 135-139. Thus, at a concentration of 20 micrograms per milliliter, each caused respective residual plasmin activities of 70, 93 and 40 percent respectively. It has also been found that synthetic humic acids made from caffeic acid and 3,4-dihydroxyphenylacetic acid cause the activity of the plasminogen activator in isolated vascular preparations of pig's ear (HP Klocking, R. Klocking and B. Helbig, Farmakol. 1984, 47 (1), 93-95). It has been found that the natural humic acids derived from the peat inhibit the hydrolysis of the ethyl ester of JV-acetyl-L-tyrosine and methyl ester of N-benzoyl-L-leucine by alpha-chymotrypsin, as well as by subtilisin: Sh. Zh. Zhorobekova and K. A. Kydralieva, Biol. Nauki 1991, 10, 151-154. It has been found that sodium humate increases the life span of crossbred rats exposed to lethal doses of 60Co radiation, as reported by GG Pukhova, NA Druzhina, LM Stepchenko and EE Chebotarev, Radiobiologia 1987, 27 (5), 650-653. It has been found that naturally occurring preparations of humic acids can stimulate the production of cytokines, including interferon gamma, inferred alpha and tumor necrosis factor alpha (AD Inglot, J. Zielinksa-Jenczylik and E. Piasecki, Arch. Immunol. Ther. Exp. (Warsz) 1993, 41 (1), 73-80; and interferon beta (Z. Blach-Olszewska, E. Zaczynksa, E. Broniarek and A. D. Inglot, Arch. I munol.Temp.Exp. (Warsz), 1993, 41 (1), 81-85). Histopathological and ultrastructural studies have shown that humic acids that occur naturally can cause morphological changes characteristic of the stimulation of thymus activity: J. A. Madej, J. Kuryszko and T. Garbulinski, Acta Pol. Pharm. 1993, 50 (4-5), 397-404. It has been shown that incubation of human umbilical vein endothelial cells in culture with either natural or synthetic humic acid results in improved cell surface expression of tissue factor activity. There are also changes in intracellular divalent calcium levels: H. L. Yang, F. J. Lu, S. L. Wung and H. C. Chiu, Thromb. Haemost. 1994, 71 (3), 325-330. Natural humic acid administered prophylactically to rats can significantly reduce the amount of gastric mucosal damage induced with ethanol. Humic acid also greatly accelerates the healing process of gastric and duodenal ulcers induced by experiments: T. Brzozowski, A. Dembinski and S. Konturek, Acta Pol. Pharm. 1994, 51 (1), 103-107. Humic acids have also been used as veterinary medicine therapies, as described and discussed by M. Kuhnert, V. Fuchs, H. Knauf and U. Knoll, Arch. Exp. Veterinarmed. 1985, 39 (3), 344-349; and M. Kuhnert, V. Fuchs and S. Golb, Dtsch. Tierarztl Wochenschr. 1989, 95 (1), 3-10. For example, H. Schultz, Dtsch. Tierarztl Wochenschr. 1962, 69, 613; 1965, 72 (13), 294-297, successfully used peat mulch to prevent the transmission of diseases in pigs' legs and snout. J. Hampl, I. Herzig and J. Vlcek, Vet. Med. (Praha), 1994, 39 (6), 305-313, has extensively studied the pharmacokinetics of sodium humate in chickens. Sodium humate chickens were administered free or encapsulated by liposomes intracardially, orally, or subcutaneously, and then several pharmacokinetic parameters were determined. The evacuation of sodium humate blood encapsulated by liposomes was higher than that of free sodium humate without considering the route of administration. On the other hand, the elimination half-life was longer after extravascular administration than after intracardiac administration. The maximum values of drug concentration indicated that the penetration of sodium humate from the injection site into the bloodstream is very slow. The biological availability of sodium humate also depended on the method of administration and dosage form. Apart from intracardiac administration, the highest bioavailability was found after subcutaneous administration of free sodium humate. It has been found that synthetic humic acid penetrates the dermis very quickly from a 1% water / oil emulsion and forms a deposit in the callus layer: W. Wohlrab, B, Helbig, R. Klocking, and M. Sprossig, Pharmazie 1984, 35 (8), 562-564. Also, around 30 minutes after external application, concentrations of 1-3% of the total amount applied are achieved, the percentage of which remains essentially unchanged in the future. The toxicity of naturally occurring humic acids is remarkably low (KD Thiel, B. Helbig, R. Klocking, P. Wutzler, M. Sprossig, and H. Schwaizer, Pharmazie 1981, 35 (1), 50-53; Riede, I. Jonas, B. Kim, UH Usener, W. Kreutz, and W. Schlickewey, Arch Orthop, Surg Trauma 1992, 112 (5), 259-264, H. Czyzewska-Szafran, Z. Jastrzebski, D Soltysis-Pawluczuk, M. Wutkiewicz, A. Hedrych, and M. Remiszewska, Acta Pol. Pharm. 1993, 50 (4-5), 373-377; HL Yang, FJ Lu, SL Wung, and HC Chiu, Thromb Haemost, 1994, 71 (3), 325-330). [The cytotoxic effects of antiviral substances, including fumic acids, are generally evaluated through biological (skill and alterations of cell morphology) and biochemical (release of 51 Cr) methods, as described by KD Thiel, U. Eichhorn, H Schwaizer, and r. Klocking, Arch. Toxicol Suppl. 1980, 4, 428-430]. It was found that the cytotoxicity (CD50) of a humic acid that occurs naturally for peripheral leukocytes of human blood (PBL) is 1-9 milligrams per milliliter. In addition, J. Schneider, R. Weis, C. Manner, B. Kary, A. Werner, BJ Seubert, and UN Riede, Virology 1996, 218 (2), 389-395, reported that the cytotoxicity of a synthetic humic acid Hydroquinone preparation for MT-2 cells was approximately 600 micrograms per milliliter. It has also been found that drugs prepared from humic acids isolated from naturally occurring soil materials are carcinogenic (test for cellular transformation of Hamster-Sirius embryo: J. Koziorowska and E. Anuszewska, Acta Pol. Pharm. 1994, 52 ( 1), 101-102) or mutagenic (T. Sato, Y. Ose, and H. Begase, Mutat Res. 1986, 252 (2), 173-178; VM Sui, AI Kiung, and TI Veidebaum, Vopr. Kurortol, Fiozioter, Lech., Fiz. Kul, 1986, 2 (3-4), 34-37, J. Koziorowska, B. Chlopkiewicz, and E. Anuszewska, Acta Pol. Pharm., 1993, 50 (4-5). , 379-382). The prenatal effects (S. Golbs, V. Fuchs, M. Kuhnert, and C. Polo, Arch. Exp.

Veterinarmed. 1982, 35 (2), 179-185) and embryotoxic and teratogenic (T. Juszkiewicz, M. Minta, B. Wlodarczyk, B.

Biernacki, and J. Zmudzki, Acta Pol. Pharm. 1993, 50 (4-5), 383-388) are also not observed with humic acid preparations at daily dose levels of 5-50 milligrams per kilogram of body weight. Local preparations are tolerated even better (VV Soldatov and MN Cherepanova, Vopr. Kurortol, Fizioter, Lech., Fiz. Kul, 1970, 35 (3), 256-259, H. Czyzewska-Szafran, Z. Jastrzebski, D. Soltysiak-Pawluczuk, M. Wutkiewicz, A. Jedrych, and M. Remiszewska, Acta Pol. Pharm. 1993, 50 (4-5), 373-377) when applied dermally in aqueous solution in amounts as high as 10 percent of weight in volume (K. Wiegleb, N. Lange, and M. Kuhnert, Dtsch, Tierarztl, Wochenschr, 1993, 200 (10), 412-416). Soil extracts, including humic, are very complex mixtures of organic and inorganic polymeric compounds whose composition varies widely depending on the source of soil and the method or methods of extraction and subsequent treatment: D. Vaughan and R. E. Malcolm, Plant Soil Sci. 1985, 16, 1-443 (see also N. Senesi, Y. Chen, and M. Schnitzer, Soil Biol. Biochem. 1977, 9, 397-403). The techniques used for the chemical characterization of soil extracts, including humic, have included capillary electrophoresis (S. Pompe, K. Heise, and H. Nitsche, J ".

Chromatogr. A, 1996, A723 (l), 215-218), ultracentrifugation (R. S. Cameron, B. K. Thornton, R. S. Swift, and A. M. Posner, J. Soil Sci. 1972, 23 (4), 394-408; A. E. Wilkinson, J. J.

Higgo, and M. N. Jones, Biochem. Soc. Trans. 1991, 15 (4), 414S), electronic paramagnetic resonance and infrared spectroscopy (G. Tollin and C. Steelink, Biochim, Biophys, Acta, 1966, 112 (2), 377-379), various solvents and other methods fractionation (R S. Cameron, BK Thornton, RS Swift, and AM Posner, J. Soil Sci. 1912, 23 (4), 394-408 CE Clapp, MH Hayes, and RS Swift, Agricultural Research Service Report Number 0000042025; MH Hayes, RL Malcolm, and CE Clapp, Agricul tural Research Service Report Number 0000042035; I. Csiky, G. Marko-Varga, and JA Jonsson, Anal Chim. Acta 1985, 278, 307-312; JA Amador, PJ Milne , CA Moore, and RG Zika, Mar. Chem. 1990, 29, 1-17), gas chromatography (I. Arsenie, H. Borén, and B. Allard, Sci. Total Environ. 1992, 115 (3), 213-220), mass spectrometry by gas chromatography (H.-R. Schulten and M. Schnitzer, Soil Sci. 1992, 153 (3), 205-224, G. Chiavari, G. Torsi, D. Fabbri, and GC Galletti, Analyst (London) 1994, 119 (6), 1141-1150), cr gel permeation omatography (B. Kosinkiewicz, Acta Microbiol. Pol. 1977, 25 (4), 387-392; S. Morí, M. Hiraide, and A. Mizuike, Anal. Chim. Acta 1987, 193, 231-238), high performance liquid chromatography (MA Curtis, AF Witt, SB Schram, and LB Rogers, Anal, Chem. 1981, 53, 1195-1199, K. Ravichandran, JJ Lewis, I. H. Yin, M. Koenigbauer, CR Powley, P. Shah, and LB Rogers, J. Chromatogr., 1988, 439, 213-226, J. Knuutinen, L. Virkki, P. Mannila, P. Mikkelson, J. Paasivirta, and S. Herve, Wat. Res. 1988, 22 (8), 985-990, M. Susic and KG Boto, J. "Chromatogr. 1989, 482 (1), 175-187), mass spectrometry (H.-R. Sechulten, G. Abbt-Braun, and FH Frimmel, Environ.Sci Technol. 1987, 21 (4), 349-357; Sorge, R. Muelller, P. Leinweber, and HR Schultenn, Fresenius' J. Anal, Chem. 1993, 345 (6-9), 697-703, M. Remmler, A. Georgi, and F.-D. Kopinke, Eur. Mass Spectrom., 1995, 2 (4), 403-407), nuclear magnetic resonance, (FJ Vila, H. Lentz, and HD Ludemann, Biochem. Biophys., Res. Commun. 1916, 72 (3), 1063-1070; G. Almendros, R. FRUND, FJ Gonzalez-Vila, KM Haider, H. KNICKER, and HD Ludemann, FEBS Lett., 1991, 282 (1), 119-121), and electrophoresis of polyacrylamide gel ( R. Klkocking, J. Chromatogr., 1973, 78, 409-416, LP Glazkova, VS Ulashchik, and FA Puntus, Vopr. Kurortol, Fizioter, Lech., Kul, 1984, 2 (2), 21-24). Many studies have been carried out on the structural characterization of soil extracts, including humic acid, by reductive degradation, as reviewed by L. B. Sonnenberg, pH.D. Thesis, University of Carolina at Chapel Hill, 1989: Dissertation Services Order No. 9007318. Models of humic structure based on the physicochemical properties of membranes have also been developed by R. L. Weershaw, Environ. Heal th Perspect. 1989, 83 (11), 191-203. R. R. Engebretson and R. Wandruszka, Environ. Sci. Technol. 1994, 28, 1934, have described efforts in the characterization of the micro-organization of humic acids dissolved in terms of their secondary structure, that is, on the way in which these large molecules are arranged in three dimensions in the solution. It is believed that the molecules are branched, ie hyperbranched fractal structures that emanate a bit like the spokes of a car wheel from a central core and which contain a large number of carboxyl and hydroxyl end groups: T. H. Mourey, S.R. Tuener, M. Rubinstein, J. M. J. Frechet, C. J. Hawker, and K. L. Wooley, Macromolecules 1992, 25, 2401 -2406. Cluster assemblies of humic acid have an average diameter of 700-1700 Angstroms; the large clusters have a fragtal dimension of 2.3: R. Osterberg and K. Mortensen, Radiat. Environ. Biophys. 1994, 33 (3), 269-276. Because the humic substances are not chemically well defined, the preparation of synthetic humic acids whose physicochemical properties mimic naturally occurring materials is very difficult, as pointed out by K. Murray and P. W. Linder, J. Soil Sci. 1983, 34, 511-523. However, there have been several notable advances in this area. In general terms, three general strategies have been developed. All depend on starting with well-defined molecules of molecular weight in the order of hydroxybenzoic acid and then causing the molecules to polymerize to form larger molecules. The methods differ in the causative factor, which can be microbial, chemical or enzymatic. Humic acids of microbial origin have been described and discussed by M. Robert-Gero, C. Hardisson, L. Le Borgne, and G. Pignaud, Ann. Inst. Pasteur (Paris) 1966, 221 (6), 750-767; and by M. Robert-Gero, C. Hardisson, L. Le Borgne, and G. Vidal, Ann. Inst. Pasteur (Paris) 1967, 223 (6), 903-505. Chemical synthesis of humic acids has been initiated by R. Klocking, B. Helbig, and associates: R. Klocking, B. Helbig, and P. Drabke, Pharmazie 1977, 32, 297; R. Klocking, B. Helbig, K. D. Thiel, T. Blumohr, P. Wutzler, M. Sprossign, and F. Schiller, Pharmazie 1979, 34 (5-6), 293-294; R. Mentel, B. Helbig, R. Klocking, L. Dohner and M. Sprossig, Biomed. Biochim. Acta 1983, 42 (10), 1353-1356; H. P. Klocking, R. Klocking, and B. Helbig, Farmakol. Toksikol. 1984, 47 (1), 93-95; K. D. Thiel, P. Wutzler, B. Helbig, R. Klocking, M. Sprossig, and H. Schweizer, Pharmazie 1984, 39 (11), 781-782; J. Hils, A. May, M. Sperber, R. Klocking, B. Helbig, and M. Sprossig, Biomed. Biochim. Acta 1986, 45 (9), 1173-1179; B. Helbig, A. Sauerbrei, R. Klocking, P. Wutzler, N. Wicht, U. Wiedemann, and G. Herrmann, J. Med. Virol. 1987, 23 (3), 303-309; K. I. Hanninen, R. Klocking, and B. Helbig, Sci. Total Environ. 1987, 62, 201-210; R. Klocking and B. Helbig, in Humic Substances in the Aquatic and Terrestrial Environment; New York: Springer-Verlag, 1989; 407-412; C. Schewe, R. Klocking, B. Helbig, and T. Schewe,. Biomed. Biochim. Acta 1991, 50 (3), 299-305; D. Schols, P. Wutzler, R. Klocking, B. Helbig, and E. De Clercq, "Acquir, Immune Defic. Syndr, 1991, 4 (7), 677-685. Normally, 10 millimoles of the compound are dissolved Phenolic starting small molecules in distilled water, the pH is adjusted to 8.5 with aqueous sodium hydroxide (NaOH), and then 2.5 millimoles of sodium periodate (NaI04) is added.The solution is heated to 50 ° C during 30 minutes and then left to stand overnight The resulting polymeric products similar to humic acid are isolated by precipitation with lead (II) nitrate [Pb (N03) 2] .The precipitated polymers are redissolved in aqueous sodium hydroxide ( pH 8.5) and heated with 8-hydroxyquinoline for 30 minutes at 100 ° C. The precipitate formed is lead (II) chelate, which is removed by filtration.The residual 8-hydroxyquinoline is extracted with chloroform and the desired polymeric material. is then precipitated from the aqueous solution by the addition n of various combinations of acetic acid, ethyl acetate and ethanol. Starting compounds that have been used for the synthesis of materials similar to humic acid include 4- [bis (p-hydroxyphenyl) methylene] -2,5-cyclohexadien-l-one (aurin), 4- [bis (3- carboxy-4-hydroxyphenyl) methylene] -2-carboxy-2, 5-cyclohexadien-1-one (aurinotr carboxylic acid), 3- (3,4-dihydroxyphenyl) propenoic acid. { caffeic acid), 1,2-dihydroxybenzene (catacol), 1, 3, 4, 5-tetrahydroxycyclohexanecarboxylic acid 3- (3,4-dihydroxyphenyl) propionate (chlorogenic acid), 3,4-dihydroxyphenylacetic acid (homoprotocatechonic acid), l - (3,4-dihydroxyphenyl) -2- (iV-methylamino) ethanol (epinephrine), 3- (4-hydroxy-3-methoxyphenyl) -2-propenoic acid (ferulic acid), 3,4-5-trihydroxybenzoic acid. { gallic acid), 2,5-dihydroxybenzoic acid (gentisic acid), 2,5-dihydroxyphenylacetic acid, (homogentisic acid), 3- (3,4-dihydroxyphenyl) propionic acid (hydrocaffeic acid), 1,4-dihydroxybenzene (hydroquinone ), 2,3-dihydroxytoluene (3-methylcatechol), 3,4-dihydroxytoluene (4-methylcatechol), 2,5-dihydroxytoluene (2-methylhydroquinone), 4,4'- (2,3-dimethyltetramethylene) -di- (1,2-dihydroxybenzene). { nordihydroguyarético acid), 1- (3,4-dihydroxyphenyl) -2-aminoethanol (norepinephrine), 3,4-dihydroxybenzoic acid (protocatechonic acid), 1,2,3-trihydroxybenzene (pyrogallol), 1,3-dihydroxybenzene (resorcinol), and 4-hydroxy-3-methoxybenzoic acid (vanillic acid). Other notable efforts on chemical synthesis of substances similar to humic acid include the studies by De Clercq and colleagues on aurintricarboxylic acid, its derivatives and related compounds: M. Cushman, P. Wang, SH Chang, C. Wild, E. Clercq, D. Schols, ME Goldman, and JA Bowen, J ". Med.

Chem. 1991, 34 (1), 329-337; M. Cushman, S. Kanamathareddy, E. De Clercq, D. Schols, ME Goldman, and JA Bowen, J. "Med. Chem. 1991, 34 (1), 337-342. Robert-Gero, C. Hardisson, L. Le Borne, and "G. Vidal, Ann. Inst. Pasteur (Paris) 1967, 223 (6), 903-909; M. Jakubiec, E. Miszczak, and J. Szczerkowska, Microbiol Act. Pol. [B] 1971, 3 (1), 63-55; R. Ansorg and W. Rochus, Arzneimi ttelforschung 1978, 28 (12), 2195-2198; J. Pommery, M. Imbenotte, A. F. Urien, D. Marzin, and F. Erb, Mutat. Res. 1989, 223 (2), 183-189; F. J. Lu and Y. S. Lee, Sci. Total Environ. 1992, 114, 135-139; K. Wiegleb, N. Lange, and M. Kuhnert, DTW Dtsch. Tierarztl Wochenschr. 1993, 100 (10), 412-416; H. L. Yang, F.J. Lu, S. L. Wung, and H. C. Chiu, Thromb. Hae ost. 1994, 71 (3), 325-330; W. Seffner, F. Schiller, R. Heinze, and R. Breng, Exp. Toxicol Pathol. 1995, 47 (1), 63-70; and J. Schneider, R. Weis, C. Manner, B. Kary, A. Werner, B. J. Seubert, and U. N. Ruede, Virology 1996, 218 (2), 389-395. Enzymatic catalytic synthesis of humic acids dates from 1961 with the work of RE Hampton and RW Fulton, Virology 1961, 13, 44-52 (see also RE Hampton, Phitophathology 1970, 60, 1677-1681), who found that phenols enzymatically oxidized inactivate phytopathogenic viruses (ie, related to plants). Normally, o / diphenol oxidase has been used for the enzymatic synthesis of materials similar to humic acid: anonymous, Zentralbl. Bakteriol. [Orig. A] 1976, 234 (2), 159-169; R. Klocking, B. Helbig, and P. Drabke, Pharmazie 1977, 32 (5), 297; K. D. Thiel, B. Helbig, R. Klocking, P. Wutzler, M. Sprossig, and H. Schweizer, Pharmazie 1981, 35 (1), 50-53; K. D. Thiel, B. Helbig, M. Sprossig, R. Klocking, and P. Wutzler, Acta Virol. 1983, 27 (3), 200-208; K. D. Thiel, P. Wutzler, B. Helbig, R. Klocking, M. Sprossig, and H. Klocking, and B. Helbig, Pharmazie 1986, 42 (12), 865-868. A direct comparison of humic acids enzymatically and non-enzymatically synthesized from caffeic and hydrocaffeic acids has shown that the two synthetic routes produce materials that differ somewhat in their efficacy for the suppression of herpes viruses type 1 and 2 (hominis): KD Thiel, P. Wutzler, B. Helbig, R. Klocking, M. Sprossig, and H. Schweizer, Pharmazie 1984, 39 (11), 781-782. The German Patent DE 3830333 Cl (March 15, 1990) issued to Wagner discloses a pharmaceutical composition comprising in part humic acid for the local treatment of the vesicular rash caused by the herpes virus. The method of preparation of the humic acid used is not revealed. U.S. Patent 4,999,202 (March 12, 1991) issued to Cronje et al. Discloses a composition having bactericidal or bacteriostatic properties and consisting of humic acid derived from oxidized carbon or a salt or derivative thereof as an active ingredient in a suitable carrier The active ingredient is preferably an alkali metal salt of humic acid derived from the carbon and the carrier is preferably water. The method of preparation involves the recovery of humic acid by precipitation, after acidification with an acid such as hydrochloric acid with a pH value of 2. European Patent Application 0537430A1 (April 21, 1993) by Riede, et al. reveals the use of natural or synthetic alkali metal or ammonium humates, modified or unmodified against viruses, especially against retroviruses such as HIV. Riede and others reveal humates that have little toxicity and are not mutagenic or teratogenic. Riede and others also reveal a specific synthetic preparation of said humates that requires a time of 10-15 days to complete the oxidation of the starting material, during which time the reaction temperature is kept below 40 ° C. The solution is acidified to pH 4-5 after synthesis, after which known purification methods are used, such as preparation chromatography, ultrafiltration, centrifugation, or electrodialysis. Organic salts other than the oxidant or the starting material are not used during or after the synthesis.

World patent application 95/08335 (published on March 30, 1995) by Zanetti, which is equivalent to US application 08 / 310,675 (filed September 22, 1994) discloses a method to inhibit infection of the Human Immunodeficiency Virus comprising contact leukocytes, peripheral blood mononuclear cells and lymphocytes of a person infected with said virus with a quantity of the anti-immunodeficiency virus of a natural preparation available on the market of humic acid. The humic acid preparations are also disclosed. The synthetic process disclosed does not employ inorganic salts other than sodium periodate for the oxidation of the starting material. The synthetic process uses the acidification of the synthesis product with 6 M HCl with a pH of less than 1. This solution is left to stand overnight. A precipitate of the synthetic product is formed which is washed several times with 1M HCl. The final step involves dehydration by freezing the precipitate. Phenolic polymers such as humic acid, when exposed to hydrochloric acid under the above conditions, as well as conditions in Cronje x202, can be chlorinated. That is, one or more chlorine atoms may possibly be added to the aromatic rings of the phenolic polymers: R. B. Wagner and H. D. Zook, Synthetic Organic Chemistry, New York: J. Wiley & Sons, March 1963, 88-147.

Other changes may also occur such as selective O-demethylation of humic acid products in the presence of hydrochloric acid: M. Fieser and LF Fieser, Reagents for Organic Synthesis, New York, Wiley-Interscience, Vol. 4, 1974, 250. It has been reported that the aqueous chlorination of humic acids results in the formation of compounds with mutagenic activity of direct action in the plate assay of Ames / Salmonella. The non-chlorinated humic acids are not mutagenic: J. R. Meier, R. D. Lingg, R. J. Bull, Mutat. Res. , 1983, 118 (1-2), 25-41. It has also been. reported that the chlorinated humic acid is hydrated by freezing contains non-volatile, mutagenic and / or direct acting alkylating agents: S. Agarwal, J. Neton, Sci. Totala Environ. , 1989, 79 (1), 68-83. A 90-day subchronic toxicology study with chlorinated and non-chlorinated humic acids was conducted using male Sprague-Dawley rats. A higher incidence and severity of hematuria has been found in the chlorinated humic acid 1.0 -g / 1 group: L. W. Condie, R.D. Lurie, J. P. Bercz, J. Toxicol. Environ. Heal th, 1985 15 (2), 305-14. In this way, synthetic methods for the production of humic acids that can possibly produce chlorinated humic acids sd be avoided. Another area of the related art pertinent to this invention consists of blood product compositions and methods for treating blood products to reduce viral and microbial activity. There is a variety of human blood products including blood platelets to meet critical medical therapeutic needs. Viral safety depends on the selection and exploration of the donor. It has been found that it is impossible to date to properly select blood products that provide the absolute guarantee that they are not contaminated by viruses. These blood products may be inadvertently contaminated with viruses such as Human Immunodeficiency Virus (HIV), Hepatitis virus, including Hepatitis A, B and C and other viruses. There is a solvent / detergent (SD) technique to treat blood products including blood platelets, but this technique is mainly limited to viruses enveloped by lipids and is known to be ineffective for non-enveloped viruses such as Hepatitis A and parvovirus B19 and picornavirus: PM Mannucci, and others, Ann. Intern. Med., 1994, 120 (1), 1-7; and L. Gurtler, Infusions ther. Trans f usionsmed. , 1994, 21 (Supplement 1), 77-9. In addition, it is necessary to separate detergents in the SD method from the blood product using extraction with soybean or castor oil and chromatography on insolubilized C18 resin: B. Hrowitz et al., Blood, 1992, 79 (3), 826-31; and Y. Piquet and others, Vox Sang. , 1992, 63 (4), 251-6. A pasteurization process has been developed to treat blood products. This process involves the thermal treatment of an aqueous protein solution sterilized at 60 ° C for 10 hours. However, the residual infectious virus of Hepatitis A has been found even after 10 hours of heat treatment of the sterilized preparation: J. Hilfenhaus and T. Nowak, Vox Sang. , 1994, 67 (Supplement 1), 62-6. Neither the solvent / detergent (S / D) process nor the pasteurization process are adequate to deactivate viruses that are totally resistant to heat and organic solvents. In this context, the human parvovirus B19 and the Hepatitis A virus are of particular interest: H. Schwinn et al., Arznneimi ttelforschung, 1994, 44 (2), 188-91. An excellent final heat treatment (100 ° C for 30 minutes) has been developed as an additional virus deactivation step to improve the safety of the factor VIII concentrate (FVIII) derived from the plasma already treated with the solvent / detergent method (S / D) during the manufacturing process. The efficiency of this heat treatment was demonstrated in the deactivation of two viruses not enveloped by lipids (Hepatitis A virus and Polio 1 virus). However, the loss of FVIII procoagulant activity during this heat treatment was about 15%, estimated both by coagulation assay, and by the orthomogen assay: S. Arrghi et al., Thromb. Haemost. , 1995, 74 (3), 863-73.

A method for treating human blood products using short wavelength ultraviolet light (UVC) irradiation has been developed for the virus inactivation and the improvement of its compatibility with proteins by reactive oxygen species attenuators. However, the recovery of blood protein was normally only 75%: S. Chin et al., Blood, 1995, 86 (11), 4331-6. In addition, it has been reported that ultraviolet light irradiation methods are not applicable to cellular blood products: C. M. Alien, Photochem. Photobiol. , 1995, 62 (1), 184-9. In summary, there remains a need for a safe, effective and simple method to treat all human blood products to reduce or eliminate the activity of lipid-enveloped and non-enveloped viruses without loss of blood product or blood product activity. The diversity of physicochemical characteristics has been well documented, as well as the wide variation in biological activity and toxicity of humic acids extracted or otherwise derived from natural soils. This diversity and variation is due to variations in factors such as the soil source, the method and methods of extraction and / or isolation and the technique or techniques used to treat the extract once it has been separated and isolated from the raw soil. The consequence of the irreproducibility of the properties of substances extracted in natural soil is that the commercial value of these materials is minimized. In addition, they become inadequate as medicines. Also, while various experimental processes have already been described that address various aspects of the isolation, synthesis and / or preparation of humic substances or similar materials, there are no reports of the preparation and isolation of said purely synthetic humic acids or similar materials by methods that they are suitable for scaling up directly to industrial levels, that they provide economically acceptable yields and that they optimize the preparation procedures from the point of view of safety and efficacy of the medicine. All known synthetic methods use methods of potentially toxic precipitation (precipitation of lead nitrate (II)) followed by complex isolation procedures, precipitation of hydrochloric acid producing potentially mutagenic compound or synthetic steps as long as 10 days. The solution is not to invent simple synthetic procedures that produce economical, safe materials whose physicochemical attributes are reproducible and at least simulate the attributes of the typical soil extracts available in the market. This invention is directed to this solution and to compositions and methods employing synthetic materials prepared according to the process of the invention. SUMMARY OF THE INVENTION One aspect of the invention in a process for preparing synthetic phenolic polymeric materials whose physicochemical properties and attributes are reproducible, and which simulate the physicochemical properties and attributes of the typical natural humic acids available in the market and other soil extracts. . This process comprises the following steps: a) dissolving one or more starting organic compounds selected from the group consisting of the compounds included in Table 1 and Table 2 in an aqueous solution comprising distilled water or sodium hydroxide; b) adjust the pH of the aqueous solution resulting from step a) between 8 and 11, if necessary; c) adding an alkaline periodate salt or alkaline earth periodate salt to the aqueous solution resulting from step b); d) maintaining the temperature of the solution resulting from step c) between 35 and 80 ° C for a period of 30 minutes to 100 hours; e) adding one or more compounds or salts selected from the group consisting of boric acid, borate salts, alkaline earth salts, transition metal salts, alkali sulfides, alkaline earth sulfides or transition metal sulfides to the aqueous solution resulting from step d ); f) allowing the aqueous solution resulting from step e) to stand with or without stirring at room temperature between 2 and 48 hours; g) removing the molecules of the solution resulting from step f) below 500 to 100 daltons; h) concentrating the solution resulting from step g); and i) removing water from the solution resulting from step h), if necessary. In one embodiment of the process, the pH of the aqueous solution resulting from step a) is adjusted to 8 and 11 by adding aqueous ammonium hydroxide, or another aqueous alkaline oxide or hydroxide, or aqueous alkaline earth metal oxide or hydroxide, or aqueous oxide or hydroxide of transition metals, or hydrochloric acid or other inorganic acid. In another embodiment of the process, the alkali metal or alkaline earth metal sulphides are added to the solution resulting from step b). Alternatively, the alkali metal or alkaline earth metal sulphides are added to the solution resulting from step c). In another embodiment of the process, transition metal sulfides are added to the solution resulting from step b).

Alternatively, sulfides of transition metals are added to the solution resulting from step c). In another embodiment of the process, any precipitate formed from the solution resulting from step f) is removed by centrifugation. In another embodiment of the process, step g) is carried out by dialyzing the solution resulting from step f) with a flow apparatus consisting of a sandwich-type membrane of molecular weight cut-off of 500-10000 daltons until the conductivity of the solution retained has dropped to 200 microsiemens or less. In another embodiment of the process after dialysis in step g), the solution resulting from step g) is concentrated in step h) using a flow dialysis apparatus that produces a retained solution such that the volume of the solution retained in the dialysis apparatus is dropped. In another embodiment of the process, the solution resulting from step g) is passed through a filter with pore size between 0.2 and 0.4 microns to produce a sterile solution. In another embodiment of the process, the solution resulting from step g) is sterilized by autoclaving between 100 and 150 ° C for 5 to 60 minutes to produce a sterile solution. In another embodiment of the process, the solution resulting from step h) is passed through a filter with pore size between 0.2 and 0.4 microns to produce a sterile solution. In another embodiment of the process, the solution resulting from step h) is sterilized by autoclaving between 100 and 150 ° C for 5 to 60 minutes to produce a sterile solution. In another embodiment of the process embodiment, mañosa or other static electricity reduction material is added to the solution resulting from step h) before removing the water from said solution in step i). In another embodiment of the process, step i) is carried out by dehydration by spray or thermally induced evaporation or vacuum or dehydration by freezing. In another embodiment of the process, the dehydrated powder from step i) is sterilized by autoclaving between 100 and 150 ° C for 5 to 60 minutes to produce a sterile powder. In another embodiment of the process, tubular, capillary, coiled, or flat dialysis membranes are used in step g) to remove molecules from the solution resulting from step f). In another embodiment of the process employing tubular, capillary, coiled, or flat dialysis membranes in step g), the solution resulting from step g) is passed through a filter with pore size between 0.2 and 0.4 microns to produce a sterile solution. Alternatively, the solution resulting from step g) employing tubular, capillary, coiled, or flat dialysis membranes is sterilized by autoclaving between 100 and 150 ° C for 5 to 60 minutes to produce a sterile solution. In another embodiment of the process employing tubular, capillary, coiled, or flat dialysis membranes in step g), the solution resulting from step g) is concentrated in step h) using a flow dialysis apparatus that produces a retained solution of such that the volume of the solution retained in the dialysis apparatus is dropped. In another embodiment of the process of the invention, the solution resulting from step g) is further dialyzed with a flow apparatus consisting of a sandwich-type membrane of molecular weight cut-off of 30,000-100,000 daltons to produce an aqueous solution of filtrate containing synthetic phenolic polymeric materials of lower molecular weight between 500 and 10,000 daltons and higher molecular weight between 30,000 and 100,000 daltons. In another embodiment of the previous process employing dialysis, tubular, capillary, coiled, or flat dialysis membranes are used for said dialysis. In another embodiment of the previous process employing tubular, capillary, coiled, or flat dialysis membranes in step g), the solution resulting from step g) is passed through a filter with pore size between 0.2 and 0.4 microns to produce a sterile solution. Alternatively, the solution resulting from step g) which used tubular, capillary, rolled, or flat dialysis membranes is sterilized by autoclaving between 100 and 150 ° C for 5 to 60 minutes to produce a sterile solution. In another embodiment of the above process employing tubular, capillary, coiled, or flat dialysis membranes in step g), the solution resulting from step g) is concentrated in step h) using a flow dialysis apparatus that produces a solution retained in such a manner that the volume of the solution retained in the dialysis apparatus is dropped. In another aspect of the invention, there is provided a blood product composition comprising an antiviral amount of a synthetic phenolic polymer material produced by the process of the invention combined with a blood product. In one embodiment of the composition of the blood product, the blood product is whole human blood. In another embodiment of the blood product composition, the blood product is human blood platelets. In another embodiment of the blood product composition of human blood platelets, the antiviral amount is an amount sufficient to reduce the activity of the Human Immunodeficiency Virus (HIV). In another embodiment of the blood product composition of human blood platelets, the antiviral amount is an amount sufficient to reduce the activity of non-enveloped viruses. Preferably, the non-enveloped virus is parvovirus or cytomegalovirus. In another embodiment of the blood product composition, the blood product is human blood serum. In another embodiment of the composition of the blood product, the blood product is a human blood protein. Preferably, the human blood protein is human serum albumin or human serum gamma-clobulin. In another embodiment of the blood product composition, the blood product is a factor of human hemophilia. Preferably, the human hemophilia factor is factor VIII or factor IX. In another embodiment of the blood product composition wherein the blood product is a human hemophilia factor, the antiviral amount is sufficient to reduce the activity of the Human Immunodeficiency Virus (HIV). Alternatively, the antiviral amount is sufficient to reduce the activity of the non-enveloped virus. Preferably, the non-enveloped virus is parvovirus or cytomegalovirus. In another aspect of the invention, there is provided a method for reducing the amount of virus in a blood product by contacting the blood product with an antiviral amount of a synthetic phenolic polymeric material produced by the process of the invention. In one embodiment of the method for reducing the amount of virus in a blood product, the contact consists of the sterile rupture of a seal in a connection path between two separate chambers, one of which contains the blood product in sterile form and the other contains the antiviral amount of the synthetic phenolic polymeric material in sterile form. In another embodiment of the aforementioned method, the contact consists of the injection of a sterile solution containing the antiviral amount to the blood product. In another embodiment of the above method, the virus is preferably the Human Immunodeficiency Virus (HIV). In another preferred embodiment of the above method, the aforementioned virus is Hepatitis A virus, Hepatitis B virus, Hepatitis C virus, parvovirus, or cytomegalovirus. In another embodiment of the above method, one or more additional blood treatment methods are employed to reduce viral activity. Preferably, the additional method of blood treatment is the solvent / detergent (SD) method. In another aspect of the invention, there is provided a composition for treating or preventing diseases of humans or animals caused by a virus comprising an antiviral amount of a synthetic phenolic polymeric material produced by the process of the invention and at least one carrier or excipient. physiologically acceptable. Preferably, the virus is the Human Immunodeficiency Virus (HIV), the Herpes Simplex Virus Type I or Type II, or it is a picornavirus. Preferably the physiologically acceptable carrier or excipient is an injectable solution excipient, an excipient of local formula, an ingestible excipient, a nasal spray excipient, a metered dose inhaler excipient, a vaginal or anal suppository excipient, or a suitable excipient for disinfection or conservation of a medical device. Another aspect of the invention provides a composition for treating or preventing diseases of humans or animals caused by microbes comprising an antimicrobial amount of a synthetic phenolic polymer material produced by the process of the invention and at least one physiologically acceptable excipient. Preferably the physiologically acceptable carrier or excipient is an excipient of injectable solution, an excipient of local formula, an ingestible excipient, an inhalant nasal spray excipient with metered dose, a vaginal or anal suppository excipient, or a suitable excipient for disinfection or conservation of a medical device. Preferably, the medical device is a contact lens, infra-ocular lens, dental prosthesis, medical device that can be implanted as a valve of the heart or a medical instrument which has contact with the body, such as an endoscope or catheter. Brief Description of the Drawings Figure 1 shows the trace of high performance liquid chromatography (HPLC) obtained for the synthetic humic acid product obtained from 2,5-dihydroxyphenylacetic acid (homogentisic acid), as described in Examples 10 and 11; Figure 2 shows the trace of high performance liquid chromatography (HPLC) obtained for a typical natural humic acid available in the market, - Figure 3 shows the expression p24 of positive HIV cells grown 6 and 8 days after the acid treatment synthetic humic acids prepared as described in Examples 10 and 11. Also shown for comparison are the results obtained for the natural humic acid that has been dialyzed and the natural humic acid that has been dialyzed and dehydrated by freezing. C + and C- are the positive and negative controls, respectively. Detailed Description of the Preferred Embodiment One objective of the present invention is to provide new and improved combinations of chemical processes for the preparation of synthetic phenolic polymeric materials, also known as synthetic humic acids, whose physicochemical properties and attributes are reproducible and which simulate the properties of the typical natural humic acids available in the market and other soil extracts, which do not contain ionic salts or other compounds of molecular weight less than 500 daltons, which have a minimum molecular weight of 500 daltons and whose processes will be suitable for expansion scale directly to industrial levels that provide economically acceptable returns. Another object of the present invention is to provide blood product compositions of human or animal comprising an antiviral amount of a synthetic humic acid prepared according to the above processes. Another object of the present invention is to provide methods for reducing or eliminating the amount of virus in blood products of humans or animals by contacting the blood products with an antiviral amount of a synthetic humic acid prepared according to the above processes. Another object of the present invention is to provide compositions for treating or preventing viral diseases of humans or animals comprising an antiviral amount of a synthetic humic acid prepared according to the above processes. Another objective of the present invention is to provide compositions for treating or preventing microbial diseases of humans or animals comprising an antimicrobial amount of a synthetic humic acid prepared according to the above processes. According to the present invention, the starting compounds used in the chemical processes used for the production of synthetic humic acids are known materials that are readily available in the market.

In general terms, the chemical processes for the preparation of synthetic humic acids of the invention are characterized by the following steps: A. Dissolve the organic starting compounds or the mixture of organic compounds in an aqueous solution comprising distilled water or sodium hydroxide. B. Adjust the pH of the aqueous solution resulting from step A) between 8 and 11, if necessary. C. Add an alkaline periodate salt or alkaline earth periodate salt to the aqueous solution resulting from step B). D. Maintain the temperature of the solution resulting from step C) between 35 and 80 ° C for a period of 30 minutes to 100 hours. E. Add 1 or more compounds or salts selected from the group consisting of boric acid, borate salts, alkaline earth salts, transition metal salts, alkali sulfides, alkaline earth sulfides or transition metal sulfides to the aqueous solution resulting from step D ). F. Allow the aqueous solution resulting from step E) to stand with or without stirring at room temperature between 2 and 48 hours. G. Remove molecules from the solution resulting from step F) below 500 to 10,000 daltons. H. Concentrate the solution resulting from step G). I. Remove water from the solution resulting from step H), if necessary. The starting organic compound in step A) above may be one, or more than one in combination, of different compounds taken from the group consisting of starting organic compounds illustrated in Tables 1 and 2. The starting organic compounds illustrated in Table 1 comprises a single benzene ring with six substituents R1-R6, wherein R1-R6 may be one of the indicated atom or functional groups, provided that at least one of R1-R6 is a functional group of hydroxy (- HO). Preferably, at least one of R1 and R6 is a functional group of hydroxy (-HO) and at least one of the remaining substituents R1-R6 contains a functional group of carboxylic acid. More preferably, two of R1-R6 are hydroxy (-HO) functional groups and one of the remaining substituents R1 and R6 contains a carboxylic acid functional group. The homogentisic acid, which is 2,5-dihydroxyphenylacetic acid, is a particularly preferred starting organic compound. Several initial concentrations of organic compounds and start up in distilled water may be employed and lower or higher limits are not uniformly required.

A solution of low concentration of sodium hydroxide, such as 0.1 Normal, can also be used as a diluent for the organic starting compound.

Picture • H -CHa-CHaCHa - (CHafcCHa -CBXCHa) * -. 10 -OH-OCHs -CHO-COaH -COaCH * -CHÍOH a fifteen - . 15 - (CHaHOH - (CHskOCEb - (CHICHO - (CHafeCO-fí - (CHs? OzCHs TABLE 1, CONTINUATION -CH (OH) 2 -CH (OH) OCH3 -CHfOCO OH -CH (OCH3) OO2H -CH (OCH3) CO2CH3 -CHÍOCEQOCHsCHO -CHCHOH (cis dr trane) -CHCHOCHa (cis or trans) -CHCHCHO (cis or trans) -CHCHCO2H (cis or trans) -CHCHCOaCHs (cis or trans) -CH2CHCHOH (cis or trans) -CH2CHCHOCH3 (cis or trans) - CH2CHCHCHO (cis or trans) -CH2CHCHCO2H (cis or trans) -CH CHCHCOCHES (cis or trans) BOX 2 Nordihidroguayarético Acid Chlorogenic Acid Epinephrine Norepinef ina Aurino Acido Aurintricarboxiliao Table 2, CONT, Tetrahydrobenzoquinone The appropriate initial concentration of the starting organic compound or compounds is determined by the synthesis performance requirements and inherent requirements, such as the upper limit of aqueous solubility of the starting organic compound or compounds. Conventional methods are used to determine the appropriate initial concentration of the starting organic compound or compounds. The pH of the aqueous solution containing the starting organic compound or compounds can be adjusted in step B) between 8 and 11 by adding aqueous ammonium hydroxide, or other aqueous alkaline oxide or hydroxide, or aqueous alkaline earthy oxide or hydroxide, or aqueous metal oxide or hydroxide of transition metals. Further, if the initial aqueous solution contains a low base concentration, such as 0.1 of normal sodium hydroxide and the pH of the initial solution is too high, an acid such as hydrochloric acid may be used to adjust the pH to the desired value. Other inorganic acids may also be used for pH adjustment. Note that if hydrochloric acid is used to adjust the pH down from a high initial value, care must be taken to prevent the pH from falling to 8. Acid conditions below pH 7 should be avoided in the presence of hydrochloric acid to eliminate the possibility for the formation of mutagenic chlorinated humic acid materials. An alkaline periodate salt or alkaline earth periodate salt may be employed as an oxidant or polymerization initiator of the starting organic compound in step C). Sodium periodate is particularly preferred. The concentration of the alkaline periodate salt or alkaline earth periodate salt is generally between 10% and 100% of the starting organic compound or compounds on a molar basis. Thus, if 10 millimoles of the organic starting compound are used, 1 to 10 millimoles of alkaline periodate salt may be used. Preferably, a molar concentration of periodate is used, which is 10% -50% of the molar concentration of the starting organic compound or compounds. More preferably, a molar concentration of periodate which is 25% -35% of the molar concentration of the starting organic compound or compounds is employed. The exact concentration that will be used can be determined by conventional synthetic performance optimization techniques. Optionally, alkali metal or alkaline earth metal sulphides or transition metal sulfides may be added to the initial aqueous solution containing the starting organic compound or compounds following step B), and immediately before, at the same time or after the addition of the periodate in the step C). The sulfides contribute to the phenolic polymer structure, the stability of the structure and its biological activity. Sodium sulfide nonahydrate is a particularly preferred sulfur. The concentration of the sulfide is generally between 1% and 20% of the starting organic compound or compounds on a molar basis. In this way, 10 millimoles of the organic starting compound are used, 0.1 to 2 millimoles of sulfur may be used. Preferably, a molar concentration of sulfide which is 5% -15% of the molar concentration of the starting organic compound or compounds is used. More preferably, a molar concentration of sulfide which is 8% to 12% of the molar concentration of the starting organic compound or compounds is employed. The exact concentration of sulfide that will be used can be determined by conventional synthetic performance optimization techniques. The adjusted pH aqueous solution containing the organic starting compound, the periodate and the optional sulfide are placed in a water bath or other thermostat heating device between 35 ° C and 80 ° C for a period of 30 minutes to 100 minutes. hours in step D). Alternatively, the aqueous solution itself can be thermostatted between 35 ° C and 80 ° C for a period of 30 minutes up to 100 hours. The temperature and time that are preferred are 50 ° for 30 minutes. After this period, the salts are added to the solution resulting from step D) alone or in combination in step E). The salts containing boron, calcium, and other alkaline earth metals, iron and other transition metals are preferred. In addition, these salts contribute to the phenolic polymer structure, its stability and biological activity. Particularly preferred are boric acid salts or borate salts containing gold such as sodium borate, such as alkaline earth salts, such as calcium sulfate dihydrate and transition metal salts., such as ferrous sulfate heptahydrate. The concentration of each of the salts employed is generally between 0.1% and 20% of the starting organic compound or compounds on a molar basis. Preferably, a molar salt concentration is used which is 0.2% to 10% of the molar concentration of the starting organic compound or compounds. More preferably, a molar concentration of salt which is 0.2% to 2% of the molar concentration of the starting organic compound or compounds is employed. The exact concentration that will be used can be determined by conventional synthetic performance optimization techniques. The solution resulting from step E) is allowed to stand at room temperature with or without agitation for a period of 2 to 48 hours in step F). Any precipitate formed in this step is removed by conventional centrifugation. The molecules are removed from the solution resulting from step F) below 500 to 10,000 daltons in step G). A variety of conventional known techniques can be employed such as chromatography and preparation, ultrafiltration or dialysis. Preferably the molecules are removed from the solution resulting from step F) using dialysis in step G) with open channel flow apparatus or screen membrane consisting of a sandwich membrane of lower molecular weight cut-off of 500-10,000. daltons until the conductivity of the solution has broth at 200 microsiemens or less. More preferably, the molecules are removed from the solution resulting from step F) by using dialysis in step G) until the conductivity of the solution has dropped to 30 microsiemens or less. A Pall Filtron Ulstrasette® tangential flow device or Ultrasette® Tangential Flow Mini-device used with a specialized Pall Filtron Ultralab® pump and reservoir system are preferred for dialysis of the solution. The conductivity of the solution processed in step G) can be conveniently monitored with a conductivity flow meter and conductivity cells. Alternatively, a simple, portable, economical combined conductivity and cell conductivity meter (e.g., a Nalcometer Model MLN) can be employed. Before removing the water from the solution in step H) above, the solution resulting in step G) can further be dialyzed with a flow apparatus consisting of a sandwich-type membrane of molecular weight cut-off of 50,000 daltons. In this case, the solution of the filtrate, not the retained solution, is stored for concentration and processing according to steps H) and I). The resulting product will have a molecular weight range of 500-50,000 daltons. If the solution resulting from steps G) or H) above should be stored as an aqueous solution for prolonged periods for application or subsequent use, for example as a solution for antiviral treatment, antiviral therapy, antimicrobial therapy, and spray or repair fertilizer Soils can be filtered through standard filters from 0.2 to 0.4 microns to eliminate bacteria and viruses, that is, it can be made sterile by filtration. Alternatively, the aqueous solution of steps G) or H) can be sterilized by autoclaving for 5-60 minutes at 100-150 ° C to produce a sterile solution. An optional final step I) in the process of the present invention involves the removal of water from the solution resulting from step H). When freeze dehydration is employed as the method of removing water in step I) above, the resulting product is a light, soft, dark colored powder that is subject to the effects of static electricity. To minimize these effects, a small amount of sugarcane or other sugar can be added to the solution resulting from step H) just before dehydration by freezing. The removal of water from the product can be carried out by means other than freeze-drying in step I) above, such as the evaporation of heat with or without vacuum, by rotary evaporation, by dehydration with dew, or by some other solvent removal technique that is convenient, as well as economical for aqueous solutions. The dehydrated powder obtained in step I) above can be sterilized by autoclaving for 15-30 minutes at 100-120 ° C to produce a sterile powder. The synthetic humic acid materials produced according to the chemical processes and the separation and isolation processes of the present invention exhibit the physicochemical properties and attributes of typical humic acids that occur naturally and are commercially available and other soil extracts. . An easy method to examine the physicochemical characteristics of the product obtained by steps from A) to H), or by modifications thereto, is high performance liquid chromatography (HPLC). The chromatographic datiloscopic pattern thus obtained from HPLC also offers a convenient element for comparing one product with another, as well as comparing each of the synthetic products with the naturally occurring humic acids and other soil extract materials. The HPLC method is therefore used to determine the reproducibility of the physicochemical properties and attributes of phenolic polymeric synthetic materials, as well as to determine whether the aforementioned properties and attributes simulate the physicochemical properties and attributes of humic acids. typical natural products available in the market and other soil extracts. The last simulation determination is done in a conventional way using HPLC; for example, by comparing visual and quantitative chromatographic HPLC fingerprinting patterns of the materials.

The fingerprint patterns of the two materials, one synthetic and one natural, do not have to be 100% identical to conclude that the physicochemical properties and attributes of the phenolic polymeric material simulates the physicochemical properties and attributes of natural humic acid. An approximate correspondence between the aforementioned HPLC fingerprint patterns is all that is required to conclude that the synthetic material simulates the natural material. In general, up to 75% of visual correspondence in 2 HPLC fingerprint patterns is all that is needed to conclude that one material simulates another. A useful fingerprint pattern for both natural and synthetic soil extract materials can be obtained as follows. The column consists of a sealing polymer, usually inverted phase PRP-1 (Hamilton Co.), With particle size of 5 microns and having 150 millimeters in length by 4.1 millimeters in internal diameter. The mobile phase consists of three solutions. Solution A is 0.1 Normal aqueous sodium hydroxide. Solution B is 0.05 Normal Prideaux universal buffer, which is made by combining 4.25 grams of sodium nitrate (NaN03), 12.37 grams of boric acid (H3B03), 23.06 grams of phosphoric acid (H3PO4), and 12.01 grams of acetic acid (CH3CH02H) with 4 liters of distilled water. Solution C is 100% methanol (CH2OH). The mobile phase gradient used for an HPLC pass consists of 40% of solution A plus 60% of solution B at the beginning, whose composition is changed in a linear manner to 100% of solution A after 20 minutes. The mobile phase is then linearly changed again to 10% of solution A plus 90% of solution C for the next 5 minutes, whose final composition is maintained for the purpose of a column wash over the next 35 minutes. The flow rate of the mobile phase is 1 milliliter per minute. The detector is visible by ultraviolet light, which is set at 340 nanometers. The diagram speed is usually 0.5 centimeters per minute. The size of the sample loop is 5-20 microliters. The solutions are prepared for analysis by dissolving 1-10 grams of dehydrated sample in 100 milliliters of 0.1 normal aqueous sodium hydroxide with a pH of 8-10. The chemical processes and separation and isolation processes of the present invention are suitable for scaling directly to industrial levels that provide economically acceptable yields. The chemical processes and separation and isolation processes of the present invention can produce yields of synthetic product approaching 100%. Approximately 0.08 to 0.65 grams of synthetic humic acid of 10 millimoles of organic starting compound or compounds may be produced in 300 ml. These procedures can be extended to pharmaceutical production scales using 10,000 to 20,000 liters or more of the initial solution containing the organic starting compound or compounds. A total yield of approximately 2.7 and 21.7 kilograms of synthetic humic acid can be achieved by using a stainless steel tank with a 10,000 liter term coating and a starting organic compound concentration of 10 millimoles per 300 ml. A single antiviral treatment can use milligrams of synthetic humic acid. 20 kilograms of synthetic humic acid represent 2 million units of antiviral product in 10 mg per unit. Even at the cost of a treatment of $ 0.10 per unit, this represents $ 200,000 of synthetic humic acid. Since the organic starting compounds used in the present invention are relatively inexpensive, the synthesis yields of the chemical processes and the separation and isolation processes of the present invention are economically very acceptable. Examples 1 to 9 illustrate the variety of starting organic compounds that can be employed in the process of the present invention. It was not considered necessary to carry out all the steps of the process of the present invention to illustrate the variety of starting compounds. More particularly, Examples 1 to 9 illustrate all steps of the process of the invention with the exception of step E). EXAMPLE 1 Preparation of a synthetic humic acid of 2,5-dihydroxybenzoic acid (gentisic acid). The starting organic compound is shown in Table 1 and consists of Ri = -C02H, R2, R5 = -OH, and R3, R4, R6 = -H. 1.55 grams (10 millimoles) of gentisic acid are dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The pH of the solution is adjusted to 8.5 with 6 Normal HCl. 0.54 grams of sodium periodate (NaI04; 2.5 millimoles) are added and the solution is placed in a water bath at 50 ° C for 30 minutes. The solution is allowed to stand at room temperature overnight. Any precipitate is removed by centrifugation. The solution is dialyzed with an open channel cut-off flow system or 3000 dalton screen membrane (Pall Filtron: Ultrasette ™ 7 Tangential Flow Device or Ultrasette ™ 7 Tangential Flow Mini Device) Used with a Specialized Pump System and Pall Filtron Ultralab ™ 7 tank. At a conductivity of 30 microsiemens or less against distilled water. The dialysis machine is then used to concentrate the solution to almost 200 milliliters. The solution can be stored at this point for additional use as an aqueous solution; or it can be dehydrated by freezing to a powder. (0.05-0.2 grams of tackifier or other suitable carbohydrate may be added to the solution before freeze-drying to reduce the effects of static electricity associated with freeze-dried powder.) The yield of the synthetic soil extract is 0.12 grams . The following examples 2-9 employ the synthesis procedure of Example 1 beginning with the pH adjustment of the solution. Example 2 Preparation of a synthetic humic acid of 3,4-dihydroxyphenylacetic acid (homoprotocatecholic acid). Table 1 shows the starting organic compound, 3,4-dihydroxyphenylacetic acid, and consists of Ri = -CH2C02H, R3, R4 = -OH, and R2, R5, R6 = -H. 1.68 grams (10 millimoles) of ophoracic acid or ho dissolve in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The remaining procedure is as follows in Example 1. The yield of the synthetic soil extract is 0.24 grams. EXAMPLE 3 Preparation of a synthetic humic acid of di- (3, 4-dihydroxyphenyl) hydroacetic acid, (dl-3,4-dihydromandlylic acid). Table 1 shows the organic starting compound, di- (3, 4-dihydroxyphenyl) hydroxyacetic acid, and consists of Rx = -CH (OH) C02H, R3, R = -OH, and R2, R5, Rs = -H 1.84 grams (10 millimoles) of dl-3,4-dihydroxymandelic acid are dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The remaining procedure is as follows in Example 1. The yield of the synthetic soil extract is 0.24 grams. Example 4 Preparation of a synthetic humic acid of aurintricarboxylic acid. The chemical structure of the organic starting compound is shown in Table 2. 4.2 grams (10 millimoles) of aurintricarboxylic acid are dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The remaining procedure is as follows in Example 1. The yield of the synthetic soil extract is 4.7 grams. Example 5 Preparation of a synthetic humic acid of 3- (3,4-dihydroxyphenyl) propenoic acid (caffeic acid). The starting organic compound is shown in Table 1 and consists of Ri = -CHCHC02H, R3, R4 = -OH, and R2, R5, Rs = -H. 1.80 grams (10 millimoles) of caffeic acid are dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The remaining procedure is as follows in Example 1. The yield of the synthetic soil extract is 0.65 grams. Example 6 Preparation of a synthetic humic acid of tetrahydroxybenzoquinone. The chemical structure of the start organic compound is shown in Table 2. 1.72 grams (10 millimoles) of tetrahydroxybenzoquinone is dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The remaining procedure is as follows in Example 1. The yield of the synthetic soil extract is 0.16 grams. Example 7 Preparation of a synthetic humic acid of 1,4-dihydroxybenzene (hydroquinone). In Table 1, the starting organic compound is shown and consists of Ri R4 = - OH, and R2, R3, R5, R6 = -H. 1.10 grams (10 millimoles) of hydroquinone are dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The remaining procedure is as follows in Example 1. The yield of the synthetic soil extract is 0.16 grams. Example 8 Preparation of a synthetic humic acid of 3, 4, 5-trihydroxybenzene (gallic acid). In Table 1, the starting organic compound is shown and consists of Rx = -CH2C02H, R3, R4 / R5 = -OH, and R2, Rs = -H. 1.70 grams (10 millimoles) of gallic acid are dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The remaining procedure is as follows in Example 1. The yield of the synthetic soil extract is 0.10 grams. Example 9 Preparation of a synthetic humic acid of 2,5-dihydroxyphenylacetic acid (homogentisic acid). In Table 1 the starting organic compound is shown and consists of Rx = -CH2C02H, R2, R5 = -OH, and R3, R4, R6 = -H. 1.68 grams (10 millimoles) of homogentisic acid are dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The remaining process is as follows in Example 1. The yield of the synthetic soil extract is 0.20 grams The following Examples 10 to 13 illustrate the entire process of the present invention including step E) Examples 10-13 illustrate that the humic acid materials produced in accordance with the chemical processes and the separation and isolation processes of the present invention exhibit the physicochemical properties and attributes of typical humic acids that occur naturally and are commercially available and other extracts of Examples 10-13 also illustrate that the therapeutic indications of the synthetic humic acids produced according to the chemical processes and the separation and isolation methods of the present invention are indications of soil extracts and humic acids in general, that is, for viral disorders and diseases of inflammatory origin, microbial no or other Example 10 Preparation of another synthetic humic acid of 3,5-dihydroxyphenylacetic acid (homogentisic acid). The starting organic compound is shown in Table 1 and consists of R = -CH2C02H, R2, R5 = -OH, and R3, R4, R6 = -H. 1.0 gram (6 millimoles) of homogentisic acid is dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The pH of the solution is adjusted to 8.5 with 6 Normal HCl. 0.32 grams of sodium periodate (NaI0, 1.5 millimoles) and 0.12 grams of sodium sulphide nonahydrate (Na2S-9H20, 0.5 millimoles) are added, and the solution is placed in a 50 ° C water bath overnight . 0.001 grams of boric acid (H3B03; 0.016 millimoles), 0.021 grams of ferrous sulfate heptahydrate (FeS04.7H20, 0.075 mmol) and 0.006 grams of calcium sulfate dihydrate (CaS04-2H20, 0.035 millimoles) are added and the solution is stirred for 2 hours at room temperature. Any precipitate is removed by centrifugation. The solution is dialyzed with an open channel cut-off flow system or 3000 dalton screen membrane (Pall Filtron: Ultrasette 7 Tangential Flow Device or Ultrasette 7 Tangential Flow Mini-Device Used with a Pall Pump and Tank Specialized System Filtron Ultralab 7). At a conductivity of 30 microsiemens or less against distilled water. The dialysis machine is then used to concentrate the solution to almost 200 milliliters. The solution can be stored at this point for additional use as an aqueous solution; or it can be dehydrated by freezing to a powder. (0.05-0.2 grams of mañosa or another suitable carbohydrate can be added to the solution before dehydration by freezing to reduce the effects of static electricity associated with dehydrated powder by freezing.) The yield of the synthetic soil extract is 0.23 grams . The HPLC trace of the synthetic sodium extract obtained in this example is illustrated in Figure 1. The peaks 1-6 are produced by this example. Peak 5 is below the infection point of peak 4 and is not overtly apparent. A first mathematical derivative of the detector signal against time can more clearly show peak 5. Figure 2 shows the HPLC trace of a typical natural humic acid available in the market. Peak 6 in Figures 1 and 2 is produced by a column wash with 90-100% v / v methanol and also contains synthetic humic acid. It can be seen that with the exception of the relative amounts of material in peaks 2, 4 and 6, the rest of the HPLC traces in Figures 1 and 2 are essentially equivalent. Thus, the synthetic process of the present invention produced a humic acid material with physicochemical characteristics that are essentially equivalent to the characteristics of a soil extract commercially available. EXAMPLE 11 Preparation of another synthetic humic acid of 2,5-dihydroxyphenylacetic acid (homogentisic acid). In Table 1, the starting organic compound is shown and consists of Ri = -CH2C02H, R2, R5 = -OH, and R3, R4, RS = -H. 1.68 grams (10 millimoles) of homogentisic acid are dissolved in 300 milliliters of 0.1 Normal aqueous sodium hydroxide (NaOH). The pH of the solution was adjusted to 8.5 with 6 Normal HCl. 0.75 grams of sodium periodate (NaI0 / - 3.5 millimoles) and 0.24 grams of sodium sulphide nonahydrate (NaS-9H20, 1 millimole) are added, and the solution is placed in a water bath at 50 ° C for the entire night. 0.006 grams of boric acid (H3B03, 0.1 millimole), 0.28 grams of ferrous sulfate heptahydrate (FeS04.7H20, 1 millimole), and 0.017 grams of calcium sulfate dihydrate (CaSO4-2H20, 0.1 millimole) are added and the solution it is stirred for 48 hours at room temperature. Any precipitate is removed by centrifugation. The solution is dialyzed with an open channel cut-off flow system or 3000 dalton screen membrane (Pall Filtron: Ultrasette ™ 7 Tangential Flow Device or Ultrasette ™ 7 Tangential Flow Mini Device) Used with a Specialized Pump System and Pall Filtron Ultralab ™ 7 tank. The dialysis machine is then used to concentrate the solution to almost 200 milliliters. The solution can be stored at this point for additional use as an aqueous solution; or it can be dehydrated by freezing to a powder. (0.05-0.2 grams of tackifier or other suitable carbohydrate may be added to the solution prior to freeze-drying to reduce the effects of static electricity associated with freeze-dried powder.) The yield of synthetic soil extract It is 0.47 grams. The HPLC trace of the synthetic soil extract obtained in this Example is identical to that described in Example 10 and is illustrated in Figure 1. EXAMPLE 12 Antiviral properties of the synthetic humic acid prepared according to Examples 10 and 11. Various Hundreds of milligrams of synthetic humic acid are prepared according to the procedures of Examples 10 and 11. The antiviral properties of these materials were assessed according to the following methods: Jurkat cells obtained from the American Type Culture Collection (Rockville, Maryland) are subcultured every fifth day using RPMI-1640 medium supplemented with 2 millimolar L-glutamine and 15% by volume fetal bovine serum (FBS). The cell counts are determined with a Coulter particle counter (Coulter Corporation, Hiaieah, Florida). The cells are infected with a plasmid construct of HIV-1, pNL4-3 (A. Adachi, HE Gendleman, S. Koenig, T. Folks, R. Willey, A. Rabson, and MA Martin, J. Virol. , 59, 284-291; the cell cultures thus treated produce high levels of HIV-1, approximately 1 x 107 particles per milliliter, as measured by electron microscopy). The infected cells are then cultured in a complete medium comprised of RPMI-1640 supplemented with 2 millimolar of L-glutamine, 15% by volume of fetal calf serum and 1% by volume of Pen-Strep (100 Units of Penicillin and 100 milligrams of Streptomycin per milliliter). The cells are monitored for approximately four weeks before their use in order to ensure a stable production of HIV-1. Before testing the antiviral efficacy of synthetic humic acid, the floating matter of the Jurkat cell culture for p24 HIV-1 production is first tested in order to establish a pretreatment baseline. After confirming the level of virus production, the growth medium is changed and the number of cells is adjusted to 1.5 x 106 cells per milliliter. Then, two days before administering the synthetic humic acid to be tested, equal volumes of transfected cells are mixed with normal, untreated cells to bring the level of virus production within the range of the HIV-1 p24 immunoassay. After 24 hours, a known amount of synthetic humic acid is added to the cell mixture. The determination of HIV-1 p24 expression after a specific number of days after the administration of synthetic humic acid is carried out with a solid phase assay designed for HIV-1 antigens (HIVAG-1, Abbott Laboratories, Diagnostic Division , Abbott Park, Illinois, Elector ELISA Quantum II from Abbott and data reduction module 1.21). Figure 3 shows the effect of synthetic humic acid prepared as described in Examples 10 and 11 on the expression p24 of HIV positive cells as measured according to the procedures of Example 12. Example Ia in Figure 3 is prepared exactly in accordance with the procedure of Example 11. Example 11b in Figure 3 was prepared according to the procedure of Example 11 with the additional step of freeze-drying the final solution. The results obtained are shown for comparison with natural humic acid which was subjected to dialysis as described in Examples 1-11; and natural humic acid that was subjected to dialysis with subsequent freeze-drying as described in Examples 1-11. The results show considerable reductions in p24 expression for all samples. In addition, on day 12, no p24 expression was detected within the experimental error of the method (none greater than the C- control). EXAMPLE 13 Toxicity of the synthetic humic acid prepared according to Example 10. Several hundred milligrams of synthetic humic acid are prepared according to the procedure of Example 10. Five units of 450 milliliters each of whole human blood are collected in CP2D systems / AS-3 Leukotrap RC-PL. the blood is left to rest for 3 hours at room temperature. Each sample is weighed and then centrifuged at 2820 revolutions per minute (2312 gravities) for 3 minutes, 44 seconds. The blood samples are then expressed through ATS-LPL filters in platelet storage bags. The filtration time is noted. The LR-PRP is centrifuged at 3600 revolutions per minute (3768 gravities) for 7 minutes. Almost 55 grams of platelet deficient plasma are removed from each sample. The platelet concentrates are allowed to stand for 90 minutes at room temperature and then are weighed and placed in a platelet incubator. The RCM1 filters are primed with AS-3 solution. The primary bags are hung at a height of 60 inches above the empty AS-3 bags, so gravity filtration occurs. The filtration time is recorded and the LR-RCC systems are hermetically sealed 3 inches below those of the RCM1 filters. Each RCM1 filter along with 6 inches of pipe and the LR-RCC, including the donor identification tube segment, are heavy. Samples are taken at this point for post-filtration test (LR-RCC). On day 1, sufficient synthetic humic acid is added to each platelet concentrate to bring its concentration to 25 micrograms per milliliter. The treated platelet concentrates are then incubated in a platelet incubator for 1 hour, after which the samples from each platelet concentrate are taken for testing. Subsequent samples are also taken on day 5 for later tests. Table 3 shows the effect of the synthetic humic acid prepared as described in Example 10, on the viability of the platelet concentrates as measured according to the procedures of this Example. The results are nominal, that is, the synthetic humic acid has no effect on the viability of the platelets (ie, it is not toxic). These results are particularly noteworthy, since it is known that blood platelets are sensitive to a variety of chemical agents. It is for this reason that few safe antiviral treatments are available for blood platelets.

Examples 12 and 13 illustrate that the synthetic humic acids prepared according to the above separation and isolation processes and methods of the present invention can be combined in antiviral amounts with blood products to form blood product compositions. Synthetic humic acids in antiviral amounts can be added to human or animal blood products, such as whole blood, blood plasma, blood platelets or other blood products containing fractions of blood, such as factor VIII of hemophilia, factors IX and V, of hemophilia , albumin, IgG, IgM or other blood proteins or blood materials to reduce or eliminate viral activity. Synthetic humic acids in antiviral amounts can be added to both liquid and solid blood products. Synthetic humic acid will have application to blood materials including all blood materials where the solvent / detergent (SD) treatment is applied. In direct contrast to the SD treatment, which is effective for non-enveloped viruses, the synthetic humic acid prepared according to the present invention has antiviral activity against enveloped and non-enveloped lipid viruses and thus has wider application. With respect to the antiviral amounts of humic acids, it is known, from the prior art, that an antiviral amount of synthetic humic acid is an amount that is useful in reducing or eliminating viral activity. Generally, an antiviral amount useful in blood product compositions for reducing or eliminating viral activity in liquid compositions of blood products is a concentration of synthetic humic acid between 5 and 1000 micrograms per milliliter of liquid composition of blood product. This same concentration range is applied to solid compositions of blood products containing dehydrated synthetic humic acid by dissolving the solution before use. The exact amount that will be used to reduce or eliminate viral activity depends on the particular virus and blood product and can be determined with conventional antiviral test procedures known in the art. Whole blood, blood plasma or other blood products supposedly contaminated or contaminated with HIV or hepatitis virus can be modified, for example, with the addition of 10 to 200 micrograms per milliliter of synthetic humic acid. Examples 14 and 15 illustrate compositions of blood products containing antiviral amounts of synthetic humic acid prepared in accordance with the processes and separation and isolation methods of the present invention.

Table 3 pH at 22 ° C pC02, mm Hq 10, mm Hq HC03, mmoi / L PV Unit No. Day l Day 5 Day l Day 5 Day 1 Day 5 Day 1 Day 5 Day 1 Day 5 1 7,466 7,394 19.3 12.8 33.5 44.4 16.8 9.5 7.0 6.6 2 7.321 7.215 21.6 14.3 9.9 22.2 13.8 7.3 6.7 6.3 3 7.320 7.276 24.4 16.6 10.3 21.3 15.6 9.7 6.7 6.5 4 7.368 7.308 20.7 14.3 13.4 22.2 14.6 8.9 6.5 6.3 5 7.457 7.454 20.1 13.8 23.7 29.0 17.1 11.6 7.7 7.4 Average 7.386 7.329 21.2 14.4 18.2 27.8 15.6 9.4 6.9 6.6 Standard deviation 0.071 0.095 2.0 14 10.2 9.8 1.4 1.5 0.5 0.6 Production Flow Production% ESC% HRS Lactate. mmol / L of WBC. x Platelets. x 1010 W No. of Day l Day l Day 5 Day 1 Day 5 Day l Day 5 Day 1 Day 5 Day 1 Day 5 Unit 1 0.1 8.3 9.0 3 3 24.2 16.9 78.0 64.0 5.1 12.1 2 0.2 14.5 14.2 3 3 27.5 20.3 81.7 71.5 6.6 13.4 3 0.4 13.3 13.4 3 3 28.7 26.3 81.7 79.4 6.3 12.4 4 0.3 11.7 12.3 3 3 22.1 19.2 81.7 77.1 6.6 13.1 5 0.3 8.9 9.1 3 3 19.1 14.4 74.7 70.2 4.5 9.7 Average 0.3 11.3 11.6 3.0 2.8 24.3 19.4 79.5 72.4 5.8 12.1 Deviation 0.1 2.7 2.4 0.0 0.4 3.9 4.5 3.1 6.1 1.0 1.4 Standard Example 14 Composition of whole human blood containing 25 ug / milliliter of a synthetic humic acid of 2,5-dihydroxyphenylacetic acid (homogentisic acid). The composition of the blood product is as follows: Complete human blood: 1 liter Synthetic humic acid: 25 mg Example 15 Composition of human hemophilia factor VIII containing a synthetic humic acid of acid 2, 5-dihydroxyphenylacetic acid (homogentisic acid). The composition of blood product is as follows: Factor VIII of human hemophilia: vial * of 1-5 ml Synthetic humic acid: 125 ug * Note: This is a vial containing sterile concentrate of highly purified lyophilized factor VIII proposed for dilution with 5ml of sterile injectable saline and containing 3900 units (IU) of factor VIII in a concentration of 100 IU / mg of protein. The synthetic humic acids prepared according to the above processes and the separation and isolation methods of the present invention can be used in antiviral amounts as defined above in methods for reducing or eliminating the amount of virus in human or animal blood products. Generally, these methods involve in some way the contact of the blood product with an antiviral amount of synthetic humic acid. Various contact elements may be employed, such as the direct injection of a sterile solution containing the antiviral amount to the blood product. A particularly preferred method involves the use of so-called "dual bag" technology for intravenous solutions. This method employs a plastic bag with two separate chambers and a connection path between them. The two cameras can vary in volume and the volume ratio between them. The two chambers may contain two different drugs or for the purpose of employing the present invention, a blood product in one chamber and the synthetic humic acid in the other chamber. The connection path is closed until the product is ready to be used. The path can be opened with a set of valves or by breaking a seal between the two chambers. The seal usually breaks without compromising the sterility of the products in both chambers. The dual bag technology for sterile solution is available from Abbott Laboratories in Illinois, McGaw in California and other companies. Alternatively, a blood product may be contacted with an antiviral amount of synthetic humic acid during the processing of the blood product before the final processing step or including the same wherein the blood product is placed inside its final container for patient use. Due to the non-toxic nature of the synthetic humic acid as prepared herein, it is not necessary to separate the humic acid from the blood product before the use of the blood product. It has already been disclosed herein that it is necessary to separate the detergents in the solvent / detergent (SD) blood treatment method from the blood product using extraction with soy or castor oil and chromatography on C18 resin. Methods for reducing or eliminating the amount of virus in human blood products using synthetic humic acid have an additional advantage over SD methods in that unlike SD methods, both lipid-wrapped and non-enveloped viruses can be deactivated. Furthermore, unlike various thermal treatments or irradiation of ultraviolet light from blood products, essentially no loss of blood product is observed with the methods and treatment of synthetic humic acid. Methods for reducing or eliminating the amount of virus in blood products using synthetic humic acid can be combined with the solvent / detergent (SD) blood treatment method or other blood treatment methods, including heat treatments, ultraviolet light irradiation other methods.

One or more of the aforementioned blood treatment methods can be combined with the humic acid treatment method. Example 16 illustrates that the synthetic humic acids prepared according to the above processes and the separation and isolation methods of the present invention can be used in antiviral amounts in methods for reducing the amount of virus in human blood products. Example 16 Method for reducing the amount of virus in human blood bags with the use of synthetic humic acid of 2,5-dihydrophenylacetic acid (homogentisic acid). The antiviral properties of the synthetic humic acid material prepared according to the procedure of Example 10 are evaluated according to the following methods: In this Example, the Bovine Viral Diarrhea Virus (BVDV) is used as an indicator virus for the activity antiviral BVDV is a virus enveloped by lipids and is known to be an excellent indicator virus for antiviral activity, including the activity of the Anti-Human Immunodeficiency Virus. A virus extract assayed for BVDV is prepared in a TCID 50 of 10E-7. Twelve pockets of blood containing blood platelets are obtained (one for each concentration of humic acid, 0.10.50 and 100 ug / ml, in triplicate). The method for reducing the amount of virus in human blood bags with the use of synthetic humic acid involves a simple addition of a sterile volumetric amount of synthetic humic acid of aqueous solution to each bag of blood. Specifically, a sterile liquid aliquot of a concentration of 100 ug / ml of synthetic humic acid in distilled water is added to each bag of blood containing between 40 and 60 ml of blood product, such that the final concentration of humic acid is of 10, 50 or 100 ug / ml. Samples of the bags are taken in the following intervals: T0 hours as a control prior to inoculation; IT hour after inoculation with the virus extract (in TI hour after inoculation, humic acid is added); at T2 hours after the inoculation, another sample is extracted. Additional samples are taken at T24 hours, T72 hours and T120 hours. Quantitative virus cultures are prepared from the extracted samples and the TCID 50s and resultant record reductions are determined for each humic acid concentration. The results of the test show that the synthetic humic acid prepared according to the present invention can be used successfully in methods for reducing the amount of virus in the blood products of humans. The synthetic humic acid prepared according to the above processes and the separation and isolation methods of the present invention can be used in antiviral amounts in compositions for treating or preventing viral diseases of humans or animals. Compositions containing synthetic humic acid are suitable for treating or preventing viral diseases of humans or animals by which it has been shown that natural humic acid materials are useful. Thus, the synthetic humic acid compositions are suitable for treating or preventing human diseases caused by the Human Immunodeficiency Virus (HIV); Herpes Simplex virus and other human viruses. The synthetic humic acid compositions are also suitable for treating or preventing diseases caused by the entire picornavirus family including the five currently known genera of viruses: (1) aftoviruses, (2) cardioviruses, (3) hepatoviruses (previously classified as enteroviruses) , (4) renteroviruses (which mainly constitute a combination of the above rhinoviruses and enteroviruses), and (5) a new genus, with only one representative to date, the ecovirus 22. Suitable compositions can be prepared for various routes of administration and viral diseases in particular. An antiviral amount of synthetic humic acid for a viral disease can be determined in particular from the known antiviral amount of natural humic acid which is known to be useful for the same viral disease in particular.

A variety of compositions can be prepared comprising an antiviral amount of synthetic humic acid and at least one physiologically acceptable excipient. Compositions comprising physiologically acceptable excipients suitable for intravenous injection, intramuscular injection, local application, oral ingestion, nasal spray administration, administration by inhalation of metered dose and vaginal and anal administration by means of suppositories can be prepared with known excipients and methods. Examples 17-21 illustrate the above compositions. EXAMPLE 17 Composition of injectable solution for treating human immunodeficiency virus (HIV) infection containing an antiviral amount of synthetic humic acid of 2, 5-dihydroxy-enylacetic acid (homogentisic acid) and excipients of solution for injection: Sodium chloride 9.00 grams Synthetic humic acid 500 milligrams Distilled water sufficient quantity to 1 liter The pH of the above solution can also be adjusted to 7.4 with 1 Normal sodium hydroxide before adding all the water. This injectable solution composition can be prepared by conventional methods to prepare sterile injectable solutions.

EXAMPLE 18 Composition of local ointment for treating infection by the human herpes simplex virus (HSV-I or HSV-II) containing an antiviral amount of synthetic humic acid of 2,5-dihydroxy-enylacetic acid (homogentisic acid) and excipients of formula local: Synthetic humic acid 3.0 grams Ketostearyl alcohol 27 grams Liquid paraffin 20 grams Soft white paraffin 50 grams EXAMPLE 19 Composition of local cream to treat infection by the human herpes simplex virus (HSV-I or HSV-II) containing an amount 2.5-dihydroxy-enylacetic synthetic humic acid antiviral (homogentisic acid) and excipients of local formula: Synthetic humic acid 2.4 grams Ketostearyl alcohol 5 grams Liquid paraffin 50 grams Distilled water add to 100 grams EXAMPLE 20 Composition of local solution to treat infection by the human herpes simplex virus (HSV-I or HSV-II) containing an antiviral amount of Synthetic humic acid of 2,5-dihydroxy-enylacetic acid (homogentisic acid) and excipients of local formula Synthetic humic acid 2.4 grams Sodium sulphide 1.0 grams Colloidal sulfur 1.4 grams Sodium chloride 2.2 grams Potassium sorbate 0.2 grams Distilled water sufficient quantity at 100 Note that the above composition contains the same amount of humic acid disclosed by Wagner in German patent DE 3830333 EXAMPLE 21 Ingestible tablet composition for treating infection by the human immunodeficiency virus (HIV) containing an antiviral amount of acid Synthetic humic acid 2, 5-dihydroxy-enylacetic acid (homogentisic acid) and ingestible tablet excipients: Synthetic humic acid 500 mg Menthol 3.6 mg Cetylpyridinium chloride 1.4 mg Cherry flavor 100 mg Glucose 500 mg Sucrose 500 mg Other excipients may also be added to the previous composition. Dyes such as Red No. 33 D &C, Red No. 40 FD &C, and other dyes can be used. Other flavoring agents can also be used in tablet formulas as well as preservatives other than cetylpyridinium chloride. The aforementioned excipients as well as other excipients not mentioned are known in the art and can be used in amounts previously used in formulas for tablets. The composition of Example 21 is also useful for treating the common cold, which is caused by members of the rhinovirus family. Nasal spray compositions containing synthetic humic acid are also particularly useful for treating the common cold. Suitable compositions and excipients comprising physiologically acceptable excipients suitable for disinfection and preservation of medical devices can be prepared with known excipients and methods. A variety of medical devices that have contact with the body can be disinfected or preserved with compositions containing synthetic humic acid. These medical devices can be disinfected or preserved before or after body contact to prevent viral infections. Contact lenses, infraocular lenses, dental prostheses, medical devices that can be implanted, such as heart valves and medical instruments which have contact with the body, such as endoscopes and catheters, can be disinfected or preserved with compositions containing synthetic humic acid.

The synthetic humic acid prepared according to the above processes and the separation and isolation methods of the present invention can be used in antimicrobial amounts in compositions for treating or preventing microbial diseases of humans or animals. With respect to the antimicrobial amounts of humic acids, it is known that an antimicrobial amount of synthetic humic acid is an amount which, from the prior art mentioned herein, is useful in the reduction or elimination of microbial activity. Generally, an antimicrobial amount useful in the compositions for reducing or eliminating microbial activity in liquid product compositions is a concentration of synthetic humic acid between 50 and 2000 micrograms per milliliter of liquid product composition. This same concentration range is applied to compositions of solid products containing dehydrated synthetic humic acid in the solution in the solution before use. Cronje et al., United States 4,999,202, discloses bactericidal or bacteriostatic compositions comprising humic acid with higher concentrations. The concentrations used by Cronje and others can also be used in the present. The exact amount that will be used to reduce or eliminate the microbial activity depends on the particular microorganism and the product and can be determined with conventional antimicrobial testing procedures known in the art. The synthetic humic acids of the present invention have antimicrobial activity comparable to the activity of the natural humic acids and other synthetic humic acids mentioned herein. Thus, the synthetic humic acids of the present invention will have activity against cryptosporidium species, C. albicans, Ent. cloacae, Prot. vulgaris, Ps. aeruginosa, S. typhimurium, St. aureus, St. epidermidis, Str. pyrogenes, Str. Mutans, E. coli and other organisms. A variety of compositions can be prepared comprising an antimicrobial amount of synthetic humic acid and at least one physiologically acceptable excipient. Compositions comprising physiologically acceptable excipients suitable for intravenous injection, intramuscular injection, local application, oral ingestion, nasal spray administration, administration by inhalation of metered dose and vaginal and anal administration with suppositories can be prepared with known excipients and methods. The local compositions of Examples 18-20 also have antimicrobial activity and illustrate the antimicrobial compositions. With known excipients and methods, compositions comprising physiologically acceptable excipients suitable for the disinfection and preservation of medical devices, such as contact lenses, can be prepared. A variety of medical devices that have contact with the body can be disinfected or preserved with compositions containing synthetic humic acid. These medical devices can be disinfected or preserved before or after body contact to prevent microbial infections. Contact lenses, intraocular lenses, dental prostheses, medical devices that can be implanted such as heart valves and medical instruments that come in contact with the body such as endoscopes and catheters can be disinfected or preserved with compositions containing synthetic humic acid. Example 22 which follows is an illustration of a composition suitable for the disinfection and preservation of contact lenses. Example 22 illustrates a bottle with multiple use solution for disinfecting, preserving (store), clean, rinse and rewet contact lenses. This solution provides the antibacterial disinfection activity required by the disinfection effectiveness guidelines of the United States Savings Fund for contact lens solutions. This solution is non-toxic and is extremely comfortable for the eye and therefore can be placed directly in the eye of the user without having to rinse with saline separately. The solution can be used with all contact lenses, such as conventional, hard, soft, rigid, gas permeable and silicone lenses, but is preferably used with soft lenses, such as those commonly known as hydrogel lenses prepared from monomers such as hydroxyethylmethacrylate, vinylpyrrolidone, glycerol methacrylate, methacrylic acid or acid esters and the like. The proteolytic enzymes used to clean contact lenses, as disclosed in U.S. Patent No. 5,356,555, may also be combined with multiple use solutions for contact lenses containing synthetic humic acid prepared according to the methods of the present invention. invention. The methods for combining proteolytic enzymes with synthetic humic acid containing multipurpose solutions and the amounts of enzyme and excipients to be employed are the same as disclosed in U.S. Patent No. 5,356,555 which is incorporated herein by reference. reference. Generally, for the purposes of the present invention, an aqueous solution containing from 0.0010 w / v% to less than or equal to 0.0100 w / v% of the disinfecting agent based on synthetic humic acid, can be used as an all-purpose solution for contact lenses. The multiple-use solutions for contact lenses containing synthetic humic acid-prepared according to the methods of the present invention have advantages over the multiple-use solutions for contact lenses of the prior art which contain other disinfecting agents. The multi-use solutions containing synthetic humic acid achieve equal or greater disinfection efficiency, while providing greater comfort for the user of contact lenses. This is a result of the inherently lower cytotoxicity or toxicity of the disinfecting agents containing synthetic humic acid as compared to the disinfectants of the prior art which are currently used for multiple-use solutions for contact lenses. The advantages of synthetic humic acid for contact lens applications are also a result of its neutral polymeric anionic nature. Current multiple-use solutions for contact lenses contain cationic polymeric disinfecting agents, such as polyhexamethylenebiguanide (PHMB) and polyquaternium 1 which have a much higher affinity for polymers inherently neutral to anionic contact lenses. However, the synthetic humic acid prepared according to the present invention is a colored material. The solutions in a concentration of 0.0025% w / v% are very light brown. In this way. For cosmetic reasons, not all solutions may be acceptable. However, because they are neutral to anionic polymers, synthetic humic acid will have a low affinity for plastic materials and therefore the materials will not be stopped if the synthetic humic acid compositions are formulated correctly. EXAMPLE 22 A multi purpose solution bottle for disinfecting, preserving (storing), cleaning, rinsing and rewetting contact lenses containing an antimicrobial amount of synthetic humic acid of 2, 5-dihydroxy-enylacetic acid (homogentisic acid). The aqueous solution has the following composition: Ingredient w / v% Synthetic humic acid 0.0025 Disodium edetate, USP 0.050 Hydroxypropyl methylcellules 0.20 Boric acid, NF 0.39 Sodium borate dehydrochloride, NF0.20 Sodium chloride, USP 0.40 Pluronic F-127 0.10 pH adjusted with NaOH or HCl 7.4 while this invention has been described fully and completely with special emphasis in several examples, it should be understood that within the scope of the appended claims, this invention may be practiced otherwise as specifically described above.

Claims (73)

1. CLAIMS; 1. A process for preparing synthetic phenolic polymeric materials whose physicochemical properties and attributes are reproducible, and which simulate the physicochemical properties and attributes of the typical natural humic acids available in the market and other soil extracts, which consists of the following steps j) dissolving one or more starting organic compounds selected from the group consisting of the compounds included in Table 1 and Table 2 in an aqueous solution comprising distilled water or sodium hydroxide; k) adjust the pH of the aqueous solution resulting from step a) between 8 and 11, if necessary; 1) adding an alkaline periodate salt or alkaline earth periodate salt to the aqueous solution resulting from step b); m) maintaining the temperature of the solution resulting from step c) between 35 and 80 ° C for a period of 30 minutes to 100 hours; n) adding one or more compounds or salts selected from the group consisting of boric acid, borate salts, alkaline earth salts, transition metal salts, alkali sulfides, alkaline earth sulfides or transition metal sulfides to the aqueous solution resulting from step d ); o) allowing the aqueous solution resulting from step e) to stand with or without stirring at room temperature between 2 and 48 hours; p) removing the molecules of the solution resulting from step f) below 500 to 100 daltons; q) concentrating the solution resulting from step g); e r) remove water from the solution resulting from step h), if necessary.
2. 2. The process according to claim 1, wherein the pH of the aqueous solution resulting from step a) is adjusted between 8 and 11 by adding aqueous ammonium hydroxide, or other aqueous alkaline oxide or hydroxide, or aqueous alkaline earth metal oxide or hydroxide , or oxide or aqueous hydroxide of transition metals, or hydrochloric acid or other inorganic acid.
3. 3. The process according to claim 1, wherein the alkaline or alkaline earth sulfides are added to the solution resulting from step b).
4. 4. The process according to claim 1, wherein the transition metal sulfides are added to the solution resulting from step b).
5. 5. The process according to claim 1, wherein the alkaline or alkaline earth sulfides are added to the solution resulting from step c).
6. 6. The process according to claim 1, wherein the transition metal sulfides are added to the solution resulting from step c).
7. The process according to claim 1, wherein any precipitate formed from the solution resulting from step f) is removed by centrifugation.
8. The process according to claim 1, wherein step g) is carried out by dialyzing the solution resulting from step f) with a flow apparatus consisting of a sandwich-type membrane of molecular weight cut-off of 500-10000 daltons up to that the conductivity of the solution-retained has dropped to 200 microsiemens or less.
9. The process according to claim 8, wherein the solution resulting from step g) is concentrated in step h) using a flow dialysis apparatus that produces a retained solution in such a manner that the volume of the solution retained in the dialysis machine is dropped.
10. 10. The process according to claim 1, wherein the solution resulting from step g) is passed through a filter with pore size between 0.2 and 0.4 microns to produce a sterile solution.
11. The process according to claim 1, wherein the solution resulting from step g) is sterilized by autoclaving between 100 and 150 ° C for 5 to 60 minutes to produce a sterile solution.
12. 12. The process according to claim 1, wherein the solution resulting from step h) is passed through a filter with pore size between 0.2 and 0.4 microns to produce a sterile solution.
13. The process according to claim 1, wherein the solution resulting from step h) is sterilized between 100 and 150 ° C for 5 to 60 minutes to produce a sterile solution.
14. 14. The process according to claim 1, where a material or other static electricity reduction material is added to the solution resulting from step h) before removing the water from said solution in step i).
15. 15. The process according to claim 1, wherein step i) is carried out by thermally induced or vacuum dehydration or evaporation or freeze dehydration.
16. 16. The process according to claim 1, wherein the dehydrated powder of step i) is autoclaved between 100 and 150 ° C for 5 to 60 minutes to produce a sterile powder.
17. The process according to claim 1, wherein tubular, capillary, coiled, or flat dialysis membranes are used in step g) to remove the molecules from the solution resulting from step f).
18. 18. The process according to claim 17, wherein the solution resulting from step g) is passed through a filter with pore size between 0.2 and 0.4 microns to produce a sterile solution.
19. 19. The process according to claim 17, wherein the solution resulting from step g) is sterilized by autoclaving between 100 and 150 ° C for 5 to 60 minutes to produce a sterile solution.
20. The process according to claim 17, wherein the solution resulting from step g) is concentrated in step h) using a flow dialysis apparatus that produces a retained solution such that the volume of the solution retained in the Dialysis machine is dropped.
21. 21. The process according to claim 1, wherein the solution resulting from step g) is further dialyzed with a flow apparatus consisting of a sandwich-type membrane of molecular weight cut-off of 30,000-100,000 daltons to produce an aqueous solution of filtrate containing synthetic phenolic polymeric materials of lower molecular weight between 500 and 10,000 daltons and higher molecular weight between 30,000 and 100,000 daltons.
22. 22. The process according to claim 21, wherein tubular, capillary, coiled, or flat dialysis membranes are used for additional dialysis.
23. 23. The process according to claim 22, wherein the solution resulting from step g) is passed through a filter with pore size between 0.2 and 0.4 microns to produce a sterile solution.
24. The process according to claim 22, wherein the solution resulting from step g) is sterilized by autoclaving between 100 and 150 ° C for 5 to 60 minutes to produce a sterile solution.
25. The process according to claim 22, wherein the solution resulting from step g) is concentrated in step h) using a flow dialysis apparatus that produces a retained solution such that the volume of the solution retained in the dialysis machine is dropped.
26. 26. A blood product composition comprising an antiviral amount of a synthetic phenolic polymeric material produced by the process of claim 1, combined with a blood product.
27. The composition of claim 26, wherein the blood product is whole human blood.
28. 28. The composition of claim 26, wherein the blood product is human blood platelets.
29. 29. The composition of claim 28, wherein the antiviral amount is an amount sufficient to reduce the activity of the Human Immunodeficiency Virus (HIV).
30. 30. The composition of claim 28, wherein the antiviral amount is an amount sufficient to reduce the activity of the unwrapped virus.
31. 31. The composition of claim 30, wherein the non-enveloped virus is parvovirus.
32. 32. The composition of claim 30, wherein the non-enveloped virus is cytomegalovirus.
33. 33. The composition of claim 26, wherein the blood product is human blood serum.
34. 34. The composition of claim 26, wherein the blood product is a human blood protein.
35. 35. The composition of claim 34, wherein the human blood protein is human serum albumin or human serum gamma-clobulin.
36. 36. The composition of claim 26, wherein the blood product is a factor of human hemophilia.
37. 37. The composition of claim 36, wherein the human hemophilia factor is factor VIII
38. 38. The composition of claim 36, wherein the human hemophilia factor is factor IX.
39. 39. The composition of claim 36, wherein the antiviral amount is an amount sufficient to reduce the activity of the Human Immunodeficiency Virus (HIV).
40. 40. The composition of claim 36, wherein the antiviral amount is an amount sufficient to reduce the activity of the unwrapped virus.
41. 41. The composition of claim 40, wherein the non-enveloped virus is parvovirus.
42. 42. The composition of claim 40, wherein the non-enveloped virus is cytomegalovirus.
43. 43. A method for reducing the amount of virus in a blood product by contacting the blood product with an antiviral amount of a synthetic phenolic polymeric material produced by the process of claim 1.
44. 44. The method of claim 43, wherein the contact consists of the sterile rupture of a seal in a connection path between two separate chambers, one of which contains the blood product in sterile form and the other contains the antiviral amount of the synthetic phenolic polymeric material in sterile form.
45. 45. The method of claim 43, wherein the contact consists of the injection of a sterile solution containing the antiviral amount to the blood product.
46. 46. The method of claim 43, wherein the virus is Human Immunodeficiency Virus (HIV).
47. 47. The method of claim 43, wherein the virus is the Hepatitis A virus.
48. 48. The method of claim 43, wherein the virus is the Hepatitis B virus.
49. 49. The method of claim 43. , wherein the virus is the Hepatitis C virus.
50. 50. The method of claim 43, wherein the virus is parvovirus.
51. 51. The method of claim 43, wherein the virus is cytomegalovirus.
52. 52. The method of claim 43, wherein one or more additional blood treatment methods are employed to reduce viral activity.
53. 53. The method of claim 52, wherein the additional method of blood treatment is the solvent / detergent (SD) method.
54. 54. A composition for treating or preventing diseases of humans or animals caused by a virus comprising an antiviral amount of a synthetic phenolic polymeric material produced by the process of claim 1, and at least one physiologically acceptable carrier or excipient.
55. 55. The composition of claim 54, wherein the virus is Human Immunodeficiency Virus (HIV).
56. 56. The composition of claim 54, wherein the virus is Herpes Simplex Virus Type I or Type II.
57. 57. The composition of claim 54, wherein the virus is a picornavirus.
58. 58. The composition of claim 54, wherein the physiologically acceptable excipient is an excipient of injectable solution.
59. 59. The composition of claim 54, wherein the physiologically acceptable excipient is an excipient of local formula.
60. 60. The composition of claim 54, wherein the physiologically acceptable excipient is an ingestible excipient.
61. 61. The composition of claim 54, wherein the physiologically acceptable excipient is a nasal spray excipient.
62. 62. The composition of claim 54, wherein the physiologically acceptable excipient is an inhaler excipient with metered dose.
63. 63. The composition of claim 54, wherein the physiologically acceptable excipient is a vaginal or anal suppository excipient.
64. 64. The composition of claim 54, wherein the physiologically acceptable excipient is suitable for disinfection or preservation of a medical device.
65. 65. Compositions for treating or preventing human or animal diseases caused by microbes comprising an antimicrobial amount of a synthetic phenolic polymeric material produced by the process of claim 1, and at least one physiologically acceptable excipient.
66. 66 The composition of claim 65, wherein the physiologically acceptable excipient is an excipient of injectable solution.
67. 67. The composition of claim 65, wherein the physiologically acceptable excipient is an excipient of local formula.
68. 68. The composition of claim 65, wherein the physiologically acceptable excipient is an ingestible excipient.
69. 69 The composition of claim 65, wherein the physiologically acceptable excipient is a nasal spray excipient.
70. 70. The composition of claim 65, wherein the physiologically acceptable excipient is an inhaler excipient with measured dose.
71. 71. The composition of claim 65, wherein the physiologically acceptable excipient is a vaginal or anal suppository excipient.
72. 72. The composition of claim 65, wherein the physiologically acceptable excipient is suitable for disinfecting or maintaining a medical device.
73. 73. The composition of claim 72, wherein the medical device is a contact lens.