L-SODの薬理生化学的検討と臨床効果(第2報)

抄録

Bovine liposomal-encapsulated superoxide dismutase (L-SOD) which was developed by A. M. Michelson has overcome the pharmacobiochemical problems (disadvantages) of the injection of SOD preparations ; the very short life span of free SOD (6 min) was to considerable extent prolonged (6-7 hr), and weak fixation and penetration (permeability) to the membranes of target cells where oxygen radicals or lipid peroxides are exerting their harms. As previously reported by us, the injection (2.5 mg twice a week) of L-SOD was markedly effective in Kawasaki's disease (mucocutaneous lymph node syndrome), intestinal ulcer of Behçet's disease, Crohn's disease and colitis ulcerosa, and lung fibrosis of progressive systemic sclerosis (PSS) and polymyositis (dermatomyositis). In addition, severe rheumatoid arthritis (RA), Sjögren syndrome and other oxygen radical-or lipid peroxide-related diseases are improved by L-SOD injection. Recently, it has been further found that L-SOD (1.5 mg twice a week) is effective in liver cirrhosis, fibrosis induced by radiation, and schizophrenics. Acute paraquat toxicosis taken for the purpose of suicide which had been completely beyond the treatment was well treated with continuous drip infusion of L-SOD. Skin ulcer lesions were also in shorter period healed and keloid formation was prevented with L-SOD injection. However, not only other free SOD preparations but also L-SOD have various problems and questions in their pharmacologic and biochemical actions in the body to be solved or to be answered. In animal experiment, it was verified that SOD does not work dose-dependently, but the dosis over optimal concentration adversely stimulate and increase inflammation. It has been the great question why only a very small amount of enzyme (1.5 mg twice a week) actually and effectively prevents inflammation ; this dosis is 1/20 to 1/150 of the SOD which usually exists in each tissue or organ in the body. Next, it is also the great question why allogeneic (human) SOD is ineffective in the diseases while heterogeneic (bovine) SOD is effective. Although in part answered by us^{1, 7)} and Michelson, why heterogeneic SOD has shown no severe allergy such as anaphylaxis? Further, regarding the clinical effectiveness of L-SOD in Behçet's disease, why L-SOD is ineffective in ocular type while it is dramatically effective in intestinal type? SOD preparations including L-SOD, although they seem to be actually recommendable for the various inflammatory diseases, there have been several problems to solved, and L-SOD is also still required to be improved, Additionally, it is not unlikely that allogeneic (human) SOD preparations are clinically effective in the diseases.