Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Hydrolases
Patent
1983-11-15
1986-08-26
Rosen, Sam
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Hydrolases
435269, A61K 3754
Patent
active
046082530
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to immobilized pepsin for use in removing immune complex from blood and to a process for removing immune complex from blood by the use of the immobilized pepsin.
BACKGROUND ART
Auto immune disorders or immune complex diseases, typified by rheumatoid arthritis, systemic lupus erythematosis (SLE), and lupus nephritis, are, as the names imply, disorders caused by a complex of various antigens and antibodies, that is, an immune complex. The mechanisms of immune complex diseases are so complicated that many points still remain for clarification; however, the diseses are considered generally to proceed as follows:
When tissues are damaged by bacterial or viaral infection, antibodies are produced against newly formed autoantigens or virally infected cells and the antibodies react with the corresponding antigens to form immune complexes. Since these immune complexes activate the complement system and platelets, vasoactive substances such as histamine and serotonin are released and the permeability of the blood vessels is increased. Then, the immune complexes in circulation enter the vessel wall whose permeabiity has been increased and deposit along the basement membrane. Polymorphonuclear leukocytes gather at the immune complex-deposited site due to the leukocyte chemotactic factors which have been formed by the reaction of the complement to the deposited immune complexes. The polymorphonuclear leukocytes, reacting with the immune complexes, release various tissue-damaging substances such as cathepsins D and E, collagenase, elastase and permeability factors, and these substances eventually damage the tissue. In patients with immune complex diseases such as SLE, levels of the complement in the serum are generally low and aggravation of the disease conditions is closely correlated with the decrease of the complement levels. This decline is thought to be due to plentiful consumption of the complement at the site of the reaction between antigens and antibodies taking place such as in the kidneys and blood vessels. Further, the immune complexes also are related to blood coagulation systems, and it is believed that the immune complexes cause serious symptoms through diverse mechanisms, for example by acceleration of fibrinoid deposition on the damaged tissues.
Currently in use for the treatment of these immune complex diseases are physiotherapy and plasma-replacement therapy in addition to medical treatment with steroids, immunosuppressive agents, anti-inflammatory agents and so forth. In particular, plasma-replacement therapy is one of the most reliable treating methods for removing immune complex, a pathogenic factor, but the advantages of this method are not being sufficiently utilized because of the difficulty in securing the supply of plasma necessary for use in the plasma-replacement.
DESCRIPTION OF THE INVENTION
The present inventors carried out many intensive investigations to develop a treating method which has the same efficacy as plasma-replacement therapy and yet does not require plasma for replacement. As a result, they have found that pepsin and a pepsin-like enzyme contained in leukocytes specifically decompose immune complex at a neutral pH region without affecting normal plasma proteins. On the basis of this finding, they completed an invention relating to a treating agent for immune complex diseases which contains this enzyme as an effective ingredient, see Japanese patent application No. 18429/1981; PCT/JP82/00037. The present invention is an improvement over that previous one, and provides a process for removing immune complex without damaging the inherent functions of plasma proteins. This process comprises treating the plasma from a patient suffering from an immune complex disease with immobilized pepsin. The invention also provides the immobilized pepsin for use in this process.
Since the major objective of plasma-replacement therapy resides in removing nondialyzable pathogenic substances from a patient's plasma, especially immune complex, the t
REFERENCES:
The Journal of Clinical Investigation, vol. 57 (1976-1975), D. Terman et al. "Degradation of Circulating DNA", pp. 1201-1212.
Butler et al.-Chem. Abst., vol. 89 (1978) p. 105700w.
The Merck Index-9th edition (1976) p. 6942.
Kosuzume Hiroshi
Mochida Ei
Ohnishi Haruo
Suzuki Yasuo
Mochida Pharmaceutical Co. Ltd.
Rosen Sam
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