No description available.

No description available.

Humic substances are a group of ubiquitous compounds formed during the decay of plant and animal residues in the environment. These substances can be divided into humic acid, fulvic acid and humin on the basis of its solubility in water as a function of pH. Fulvic acid is the fraction that is soluble in water under all pH conditions and is usually extracted from brown coal and is therefore associated with high levels of heavy metals. These heavy metal levels have become a point of concern and a unique method for synthesizing fulvic acid from a carbohydrate source has been subsequently developed and patented in an attempt to address this problem. The purpose of this study was therefore, to test the topical and systemic safety and efficacy of this new carbohydrate derived fulvic acid (CHD-FA) product. Initial in vitro screening using the Kirby-Bauer disk diffusion method indicated that the product was active against the Staphylococcus aureus test organisms used (ATCC 12600 and P3938). Results showed that not only was it as effective as the oxacillin control, but in the case of a more virulent strain of S. aureus, the CHD-FA (3.9% w/v) proved more active. Subsequently, the ability of the product to cross full-thickness skin was ascertained using Franz-type diffusion cells fitted with 100ìm skin disks obtained from rats. At the end of a 12-hr period, results indicated that up to 20% of the CHD-FA at a pH of 2.9 was able to cross the skin barrier. Divided into 6 phases, extensive animal safety studies were conducted on the product. In phase I, toxicity and sensitivity to topical application was examined by applying the product to the ears of mice over a period of 30 days. Phase II and III was undertaken to study the long term effects (6-weeks and 6-months) of CHD-FA ingestion (150 mg/kg body mass) whilst phase IV tested the effects of CHD-FA ingestion on pregnant rats and their off-spring. Phase V was an acute toxicity study in which rats received a single oral dose of CHD-FA (150mg/kg bw) and then observed for a period of 7 days. Phase VI was a 6-week chronic study in which the animals received 100mg/kg bw daily for the duration of the experiment. Results obtained in all studies showed that CHD-FA is safe for topical as well as, oral use at the doses tested. In addition, it is safe for use during pregnancy. Finally, the in vivo anti-microbial efficacy of the CHD-FA was examined using an infected wound healing model. A pilot study indicated that the animals used should be immunocompromised and the wounds inoculated with a Staphylococcus aureus (ATCC 12600) concentration of 1x1010 CFU/ml. Results from the main study showed that topical applications of the CHD-FA (pH 1.98) product at a concentration of 1.75% w/v over the 5-day period produced a wound healing pattern similar to that of the positive fuscidic acid control. In contrast, animals receiving an oral treatment of the product did not produce a pattern different from that of the water control group. In conclusion, CHD-FA has been shown to be safe and effective in treating S. aureus infections in vitro and in animal models. This study indicates that the next phase of human studies is certainly warranted. / Dissertation (MSc)--University of Pretoria, 2009. / Pharmacology / unrestricted

An ion-specific electrode measured cupric ion activity modulated by fulvic acid (FA) and pH in a series of modified Frog Embryo Teratogenesis Assay- Xenopus (FETAX) toxicity assays. Hydrogen ion concentration was the primary determinant of cupric ion activity, while FA played a smaller but significant role. Fulvic acid was a weak copper complexing agent at pH 5.50. At pH 5.50 there was slight reduction of ionic activity and a subsequent attenuation of copper toxicity with 5.0 mg/L FA. At pH 7.50, FA also had a mild attenuating effect on copper toxicity. At pH 6.50, copper was strongly complexed by FA at total copper (TCu) concentrations below its pH-dependent solubility limit. At TCu concentrations above the solubility limit FA enhanced toxicity. There was more cupric ion activity measured in the presence of 0.5 and 5.0 mg/L FA than without it at TCu concentrations above the solubility limit. The proposed mechanism for this behavior was FA action as a nucleation inhibitor. Under the chemical conditions of the pH 6.50 experiments, a stable supersaturation of copper was formed, resulting in a more toxic aqueous matrix.

Organic acids are usually the reactants which proceed in chlorination reaction into products of disinfection by-products in water treatment plant. The purpose of this study is by using tests of kinetics and equilibrium adsorptions to investigate adsorption characteristics and kinetic model evaluations of selected organic acid in solution. We use commercial carbon nano-tube for the adsorbents. The major factors in adsorption tests include the concentration of fulvic acid (a typical organic acid in raw water), pH, ionic strength and temperature. Experiment results exhibited kinetic adsorption reached equilibrium about 120 minutes, the adsorption capacity increased with concentrations increasing of fulvic acid and decreased with ionic strengths. The best selection in kinetic models evaluation, fitting models such as Modified Freundlich equation, Pseudo-1st-order equation and Pesudo-2nd-oder equation is Modified Freundlch equation model. In addition, intraparticle diffusion equation model was fitted well and showed adsorption process was controlled with pore diffusion. The maximum adsorption capacity varied from 26.094 to 20.772 mg/g when temperature ranging from 4 to 45¢J. Isotherm adsorption results were fitted on Langmuir and Freundich models. The £GG¢X values ranged from -0.930 to -1.014 kcal/mol, £GH¢X:-1.561 kcal/mol and £GS¢X:-2.02 cal/mol. Thermodynamic parameters indicated that the adsorption is spontaneously and an exothermic reaction. Adsorption of fulvic acid by carbon nano-tube has a good performance when operation conditions of higher fulvic acid concentration, lower ionic strength, lower pH and lower temperature.

Objectives: In this pilot study, our intention was to ascertain what formulation of a carbohydrate-derived fulvic acid (CHD-FA) topical applicator was optimal for patients to use during a larger study where the efficacy of fulvic acid (CHD-FA) in treating moderate acne vulgaris will be investigated. Methods: 15 individuals with inflammatory acne with an acne grade of III or lower were asked to volunteer for the study. They were split into 3 groups. Each group was asked to use a different formulation (a cream base, gel base and wet applicator formulation) each week. After each week, the individuals returned to fill out a questionnaire evaluating the formulation they used that week. They were also examined by the clinician for any possible side effects, and given the next formulation to use for the following week. The trial was 3 weeks long, and after using all 3 formulations the individuals were asked to fill out a final questionnaire evaluating all 3 formulations. The clinician was also asked to fill out a questionnaire giving his/her opinion on the formulations. Results: The results did not give conclusive evidence of one particular formulation being favored above all the others. All the formulations performed more or less equally as well. According to the final questionnaire, 6 out of the 15 individuals were most satisfied with the wet applicator, 4 out of 15 preferred the cream base and 5 out of 15 preferred the gel base. 5 out of 15 individuals were least satisfied with the wet applicator, 3 out of 15 with the cream base, and 7 out of 15 were least satisfied with the gel. While there was no conclusive indication for one particular formulation, there were some common complaints or observations by individuals about each formulation. Most individuals said the wet applicator had an initial burning sensation to the skin upon application, but it disappeared a few seconds after application. Many individuals said they felt the cream base was oily and made the skin appear oily after application. The gel base was said to smell the worst, along with the wet applicator, while the cream smelt the least. A few individuals complained that the gel left a residue on the skin. Conclusion: While the study did not give a clear indication of one particular formulation that was preferred by individuals, it did produce interesting results that can be used to make some of the formulations more favourable. In the main trial, further investigation will be done to optimize the formulation. / Dissertation (MSc)--University of Pretoria, 2010. / Pharmacology / unrestricted

The Supercritical Fluid Extraction (SFE) technique was used to fractionate Suwannee River reference fulvic acid (FA). The fractions were characterized by gas chromatography (GC) and reversed-phase high performance liquid chromatography (RP-HPLC). A SFE fractionation method was developed using stepwise gradient of supercritical CO₂ and methanol. Three FA fractions were separated. The average mass recovery was 102% with the coefficient of variation of 2.8%. The fractionation dynamics and the difference in the ratios of UV absorption to fluorescence emission indicate the real fractionation of the FA. The HPLC chromatographic peak patterns and the spectra of the corresponding peaks were almost indistinguishable. The overall results of this research support the argument that FA exhibits polymer-like molecular structure.

High Performance Liquid Chromatography (HPLC) was used to investigate the utility of this technique for the analytical and preparative separation of components of aquatic fulvic acids (FA). Three modes of HPLC namely adsorption, anion exchange and reversed phase were evaluated. Aquatic fulvic acids were either extracted from surface water and sediment samples collected from the Southwest of the U.S., or were provided in a high purity form from the USGS. On the adsorption mode, a major fraction of aquatic fulvic acid was isolated on a semipreparative scale and subjected to Carbon-13 NMR and FAB Mass Spectroscopy. Results indicated that (1) The analyzed fraction of fulvic acid contains more aliphatic than aromatic moieties; (2) Methoxy, carboxylic acids, and esters are well-defined moieties of the macromolecule; (3) Phenolic components of the macromolecules were not detected in the Carbon-13 NMR spectrum possibly because of the presence of stable free radicals. Results of the anion exchange mode have shown that at least three types of acidic functionalities in aquatic fulvic acid can be separated. Results also indicated that aquatic fulvic acid can be progressively fractionated by using subsequent modes of HPLC. Results of reversed phase mode have shown that (1) The fractionation of aquatic fulvic acid by RP-HPLC is essentially controlled by the polarity and/or pH of the carrier solvent system; (2) Under different RP-HPLC conditions aquatic fulvic acid from several locations are fractionated into the same major components; (3) Fulvic acid extracted from water and sediment from the same site are more similar than those extracted from different sites; (4) Cationic and anionic ion pair reagents indicated the presence of amphoteric compounds within the polymeric structure of fulvic acid. Each mode of HPLC provided a characteristic profile of fulvic acid. The results of this research provided basic information on the behavior of aquatic fulvic acids under three modes of HPLC. Such informations are prerequisite for further investigation by spectroscopic methods.

Thesis (Ph.D.) - Carleton University, 2005. / Includes bibliographical references (p. 292-309). Also available in electronic format on the Internet.

Humic substances, such as the closely related humic and fulvic acids are ubiquitous, naturally occurring organic macromolecules of complex but undefined structure. These compounds are known complexing agents due to their supramolecular like structures and are capable of binding a wide variety of compounds. Numerous studies have confirmed that humic and fulvic acids exhibit diverse medicinal and therapeutic properties. For this reason, alternative or “natural” medicinal preparations rich in these substances are being self-administered, often concomitantly with conventional drugs. The possibility exists that these humic substances, found in the alternative medicinal products, may result in drug-drug interactions and bind to simultaneously ingested drugs. Complex formation may affect absorption and alter overall bioavailability. Changes in these parameters may lead to reduced therapeutic effect or toxic side effects of prescribed drugs in patients. Similarly, these humic substances may bind to and alter the uptake of ingested nutrients, such as vitamins and minerals, obtained from food sources as well as dietary supplements. Changes in absorption may result in a loss of proper physiological functioning in the body or in unwanted effects of overdose. This study investigated the effect of fulvic and humic acids on the absorption of commonly administered classes of drugs, vitamins and minerals using the everted mouse gut model that was successfully used to assess the membrane transport of the test compounds. This model made use of everted segments of excised intestinal tissue placed in Krebs Ringer Buffer (pH7.4), where physiological functioning of the tissue is maintained for up to two hours after excision. The amount of test compound which crossed through the intestinal membrane without and in the presence of each humic substance was quantified using LC-MS/MS methods developed for each of the drugs and vitamins, and ICP-MS, in the case of the minerals. The amount of test compound absorbed alone was compared to the amount absorbed when in the presence of each humic substance. Changes in the uptake, for each test compound was noted, the extent of the absorption increase or decrease was compound specific. The changes in absorption observed could be attributed to changes in compound solubility and mechanism of transport across the intestinal membrane once in complex. Drugs and vitamins were seen to be more prone to decreases in absorption in the presence of the humic substances, whereas the majority of the minerals showed significantly increased absorption. Binding of the minerals to the humic substances through chelation, and not complex formation, could have a greater effect on compound solubility. Health care professionals, as well as individuals ingesting these and other substances concurrently, should be aware of the potential effects on absorption that may occur due to drug-drug interactions in order to avoid a loss of therapeutic/physiological activity or negative toxic symptoms. / Dissertation (MSc)--University of Pretoria, 2015. / tm2015 / Pharmacology / MSc / Unrestricted