Clinical investigation of the value of synthetic hyaluronidase inhibitors in rheumatoid arthritis.

The possible role of hyaluronidase in the pathogenesis of rheumatic diseases was first suggested some ten years ago (Wallenfels, 1941; Hahn, 1944), since which time the subject has received a fair amount of attention. Certain observations in the literature suggest some interrelationship between the pathological changes of the mesenchymal tissue and an imbalance of the hyaluronidase-hyaluronic -acid system. In rheumatoid arthritis the viscosity of the joint exudate is lower than that of synovia in normal subjects (Robertson and others, 1940). The degree of polymerization of the hyaluronic acid in such exudate is likewise lowered (Ropes and others, 1947). It has also been shown that in rheumatoid arthritis the viscosity of the joint exudate can be increased by intra-articular injection of cortisone *(Bauer, 1950; Ekman and others, 1952). The in vitro inhibitory action of the exudate on hyaluronidase is also appreciably enhanced after such an injection (Ekman and others, 1952). While studying various substances for their effect on the enzymatic breakdown of hyaluronic acid, it was found that certain polycondensed diphenylmethane and triphenylmethane derivatives possess the power strongly to inhibit such hydrolysis in vitro (Hahn, 1952). Some of these substances were also tried in animal experiments and proved to be also strong inhibitors of hyaluronidase in vivo (FabinyiSzebehely and others, 1952). The purpose of the present investigation was to find whether these substances might be of any value in the treatment of rheumatoid arthritis.