Visklear Mechanism of Action

ATC code: S01XA20 - artificial tears and other indifferent preparations; Belongs to the class of other ophthalmologicals.
Pharmacology: Pharmacodynamics: Sodium hyaluronate is a polysaccharide (glycosaminoglycan) consisting of a sequence of disaccharide units, linked to each other by a β1 - >3 bond. This disaccharide unit repeats itself, forming a linear chain of high molecular weight which, in physiological saline solution, assumes a random coil configuration characterized by a large hydration volume. The sodium hyaluronate used in Visklear is obtained by bacterial fermentation and purification and is comprised of a specific fraction with a high degree of purity. The most important property of sodium hyaluronate is its viscoelasticity. This physicochemical property mechanistically leads to the following actions after topical instillation to the eye: 1) During blinking, shear stress causes the sodium hyaluronate molecules in solution to align with one another; as a result, the solution becomes elastic and relatively nonviscous, and spreads easily over the surface of the cornea.
2) Between blinks, the molecules of sodium hyaluronate form a tangled meshwork, and the solution becomes less elastic and more viscous; consequently, the precorneal tear film is stabilized and the residence time of the solution on the surface is maximized. Due to the coiled structure of the sodium hyaluronate molecule, Visklear is highly effective in entrapping water. With effective water entrapment, the rate of tear evaporation is slowed. Sodium hyaluronate solutions adhere to the mucin layer of the precorneal tear film. These physicochemical properties of the molecule, together with observed pharmacodynamics effects, such as increased corneal wound healing, ameliorate the signs and symptoms typically associated with dry eye disease. Sodium hyaluronate promotes migration of human corneal epithelial cells in vitro, leading to beneficial effects on corneal wound healing.
Pharmacokinetics: Due to its high molecular weight, sodium hyaluronate is not expected to pass through the conjunctiva and the corneal epithelium. Following intraocular administration of sodium hyaluronate, the t½ for elimination of the product from the aqueous humor was around 10.5 hours and no product was detected 24 hours after administration. After parenteral administration of sodium hyaluronate, this molecule is efficiently metabolized in the liver (t½=2.5 to 5.5 minutes).
Toxicology: Preclinical safety data: No maternal toxicity, fetal toxicity, or teratogenic effects on the fetuses of treated dams (rats or rabbits) has been observed after subcutaneous sodium hyaluronate administration at doses up to 50 mg/kg/day. Sodium hyaluronate has shown no mutagenic or clastogenic potential in bacterial assays and cytogenetic assays conducted both in vitro and in vivo. No toxic effects following acute and subacute topical ocular administration in albino rabbits and rabbits with pigmented eyes; no acute toxic effects following injection into the anterior chamber or vitreous body of monkey eyes; and no acute toxic effects in mice or rats following oral, intraperitoneal, or subcutaneous administration. Chronic administration studies of sodium hyaluronate in rats or dogs following subcutaneous administration showed no toxic effects, with the exception of local tissue hardening and/or edema at the injection site which was reversible. No antigenicity was detected in guinea pigs, mice, or rabbits after parenteral administration.