CLINICAL PHARMACOLOGY
Hyaluronidase is a spreading or diffusing substance, which modifies the permeability of connective tissue through the hydrolysis of hyaluronic acid, a polysaccharide found in the intercellular ground substance of connective tissue, and of certain specialized tissues, such as the umbilical cord and vitreous humor. Hyaluronic acid is also present in the capsules of type A and C hemolytic streptococci. Hyaluronidase hydrolyzes hyaluronic acid by splitting the glucosaminidic bond between C1 of the glucosamine moiety and C4 of glucuronic acid. This temporarily decreases the viscosity of the cellular cement and promotes diffusion of injected fluids or of localized transudates or exudates, thus facilitating their absorption.
Hyaluronidase cleaves glycosidic bonds of hyaluronic acid and, to a variable degree, some other acid mucopolysaccharides of the connective tissue. The activity is measured in vitro by monitoring the decrease in the amount of an insoluble serum albumen-hyaluronic acid complex as the enzyme cleaves the hyaluronic acid component.
When no spreading factor is present, material injected subcutaneously spreads very slowly, but hyaluronidase causes rapid spreading, provided local interstitial pressure is adequate to furnish the necessary mechanical impulse. Such an impulse is normally initiated by injected solutions. The rate of diffusion is proportionate to the amount of enzyme, and the extent is proportionate to the volume of solution.
Knowledge of the mechanisms involved in the disappearance of injected hyaluronidase is limited. It is known, however, that the blood of a number of mammalian species brings about the inactivation of hyaluronidase. Studies have demonstrated that hyaluronidase is antigenic; repeated injections of relatively large amounts of this enzyme may result in the formation of neutralizing antibodies.
The reconstitution of the dermal barrier removed by intradermal injection of hyaluronidase (20, 2, 0.2, 0.02, and 0.002 Units/mL) to adult humans indicated that at 24 hours the restoration of the barrier is incomplete and inversely related to the dosage of enzyme: at 48 hours the barrier is completely restored in all treated areas.
Results from an experimental study, in humans, on the influence of hyaluronidase in bone repair support the conclusion that this enzyme alone, in the usual clinical dosage, does not deter bone healing.
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