HA is found in many tissues of the body and is a major component of the extracellular matrix. It isinvolved in numerous physiological processes, such as cell proliferation, cellular function, tissue hydration and joint lubrication.
HA also plays a fundamental role in every phase of tissue repair, including inflammation, cell migration, angiogenesis, re-epithelialization and scar formation due to its physico-chemical (hygroscopic, rheological and viscoelastic) and biological properties. Hyaluronic acid-based medications have been found to facilitate wound repair and have proved more effective than growth factors in promoting healing while also reducing scar formation.
HA has consequently become widely used not only to improve wound healing, but also as a medical treatment and prevention for a large number of the following connective tissue disorders and problems: fractures, hernias, glaucoma, keratoconus, detached retinas, osteoarthritis, TMJ, vocal cord insufficiency, cartilage damage and ligament healing. Moreover, it provides soothing relief of dryness, itching and burning of the skin.
Glycine is a non-essential amino acid and has anti-inflammatory, cytoprotective and immunomodulation properties.
It is a fundamental component of several important biological molecules, such as collagen and acts as a biosynthetic intermediate in numerous metabolic reactions.
Current research has demonstrated that endothelial and epithelial cells contain glycine-dependent chlorine channels and that when these channels are stimulated, cutaneous barrier repair is accelerated, indicating that glycine plays a crucial role in skin barrier homeostasis.
A possible use of a Zinc-Taurine combination for therapeutic purposes as, for example, the treatment of lesions of the oral mucosa, can be justified on the basis of two possibilities of therapeutic benefit afforded by the combination of the two components:
- Zinc and Taurine possess, separately, favorable properties which contribute to the therapeutic benefit (additive effect).
- The combination of Zinc and Taurine gives rise to favorable properties, not possessed by the components separately (synergistic effect).
- The mechanism whereby Taurine and Zinc exert some synergistic effects is unclear. There are, however, some indications that may help shedding light on this issue.
- The addition of Taurine, but not other amino acids, in an amino acid glucose solution, led to a constant increase in Zinc uptake by fibroblasts.
- Taurine and Zinc have both been reported to possess stabilizing effects on biological membranes. If these two agents act through different mechanisms in order to induce such membrane-stabilization, then a synergistic outcome of these two different mechanisms of action would be reasonable.
The intended use of a Zinc-Taurine combination for the topical treatment of lesions of the oral mucosa is of considerable interest. A significant body of literature is available on biological activities of Zinc, Taurine, and some also on the Zinc-Taurine combination which represent a sound rational for the planned indication. Moreover, the product polapreZinc (Zinc-carnosine), which bears similarities to the planned Zinc-Taurine combination, is being marketed in Japan for the treatment of gastric ulcers and has been reported to be active in many animal models of injuries of the gastrointestinal mucosae. These observations suggest that a Zinc-Taurine combination may be equally effective in similar indications.
The anti-inflammatory properties of Zinc gluconate, Taurine or their combination as a complex was investigated using a Caco-2 (epithelial) in vitro cell assay. In this study monolayer Caco-2 cells were grown in culture. Cells were then treated with Doxorubicin, Lipopolysaccharide (LPS) or Dextran Sulfate Sodium (DSS). Serial dilutions of Zinc gluconate, Taurine or a mixture of Zinc-Taurine were delivered as a complex. Following an incubation period, cell culture supernates were evaluated for expression of IL-6 and IL-8, two pro-inflammatory cytokines associated with aphthous ulcers and oral mucositis lesions.
The results of this study demonstrated that Zinc gluconate and Taurine inhibited IL-6 and IL-8 expression in a dose dependent manner. The experiment also revealed that the monodentate/bidentate Zinc-Taurine complex was superior inhibiting IL-6 and IL-8 compared to Zinc gluconate alone or Taurine alone. The synergy and increased biological activity of BMG’s Zinc-Taurine compositions is the basis of the Company’s GelX® family of products designed to treat mucosal inflammation by improving the potency and delivery of essential mineral nutrients.