Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2000-04-18
2002-03-12
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S429000, C514S469000, C548S517000, C548S529000, C549S469000, C549S491000
Reexamination Certificate
active
06355669
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a therapeutic or prophylactic agent for glomerulonephritis, lupus nephritis, idiopathic thrombocytopenic purpura or autoimmune anemia, which comprises a retinoic acid receptor (RAR) agonist as an active ingredient. In particular, the present invention relates to a therapeutic or prophylactic agent for systemic erythematosus, glomerulonephritis, lupus nephritis, idiopathic thrombocytopenic purpura or autoimmune anemia, which comprises a retinoic acid receptor subtype &agr; (RAR&agr;) agonist as an active ingredient.
PRIOR ART
1) Glomerulonephritis
Glomerulonephritis is generally called nephritis where continuous albuminuria and hematuria are clinically observed, and shows a morbid state in which renal functional disturbance and complications of edema, high blood pressure and cardiac insufficiency due to storage of sodium occur in some cases.
Pathogenically, glomerulonephritis can be defined as a glomerular disease showing an increase in mesangium (phonetic transcription) cells and/or substrate in renal glomeruli.
The most universal idea on the mechanism of the onset of glomerulonephritis is that immune reaction products occurring on glomeruli damage the glomeruli. It is also evident from the fact that the damage is caused by heteroantibody and host antibody in an animal experiment. Masugi experimentally created glomerulonephritis by intravenously administering duck-derived nephrotoxic serum against rabbit renal tissues into normal domestic rabbits, and domestic rabbit-derived nephrotoxic serum against rat renal tissues into rats, thus demonstrating that glomerulonephritis is generated by an immunological mechanism (Masugi, M., Beitr. Pathol. Anat., 91, 82-112, 1933, Masugi, M., Beitr. Pathol. Anat., 92, 429-466, 1934). Since fluorescent antibody techniques were introduced for renal materials in biopsy in the 1960's, there have been reported a large number of data suggesting that an immunological mechanism is involved in generating glomerulonephritis in humans as well. In nephritis caused by these immune reactions, sedimentation of an antigen-antibody immune complex (IC) onto glomeruli is particularly important.
From the previous results of studies on animal experiment models, nephritis caused by precipitation of IC in circulating blood and nephritis by formation of IC in situ are being considered. The former is nephritis caused by binding a protein antigen originally unrelated to glomerular tissues to its corresponding antibody in blood, to form IC which is then precipitated on a glomerular sling wall or on mesangium. The latter includes 2 types of nephritis: one is caused by IC formed by binding an antibody against a renal tissue antigen (unique component in glomerular basement membrane and glomerular cells) directly to glomeruli, and the other is caused by IC formed by precipitation of an extraneous antigen via electrical charge or other affinity on glomeruli and subsequent binding of its corresponding antibody to the glomeruli in situ. The site on which IC is precipitated includes mesangium observed in endothelial cells and IgA nephropathy, in addition to epithelial cells observed in human nephropathy originating in membrane. The factors determining the precipitation site include the size of immune complex, the electric charge of antigen, antibody and immune complex, the binding force between antigen and antibody, and type and subclass of antibody. These factors are involved in precipitating an immune complex in blood or forming an immune complex in situ followed by activation of complements to initiate inflammation reaction.
Major therapeutic agents used at present for glomerulus nephritis include anti-platelet agents, anti-coagulating agents, adrenocortical steroids and immunosuppressive agents. Among these, as described above, the immunological mechanism is involved considerably in the onset of nephritis so that conventional therapy for nephritis is based on adrenocortical steroids inhibiting immune response.
The nephrosis syndrome is a disease to which adrenocorticotrophic steroids are most suited. However, the glomerulus nephritis as a causative disease for the nephrosis syndrome has various types ranging from the primary to secondary one, thus revealing that thereactivity of steroids to the nephritis syndrome is varied depending on the type of nephritis. For example, the complete remission of minimal change nephrotic syndrome (MCNS) is achieved in 80 to 95% cases by steroids. However, the effect of therapy with steroid is hardly expected except for only the case of IgA nephropathy where the degree of albuminuria is moderate while renal function is maintained, and in only this case, the therapy with steroid is performed. About ⅔ of patients with acute nest-like glomerular sclerosis respond to steroids, but the other ⅓ patients are resistant to steroids and advance to terminal-stage renal insufficiency, and patients with chronic glomerular sclerosis are also hardly responsive to steroids. Although a reduction in albuminuria in nephropathy originating in membrane (glomerulonephritis originating in membrane) is recognized by use of steroids for aprolonged period of time, stringent evaluation of this therapy is still not be established. Further, secondary lupus nephritis is classified into I to IV types in renal biopsy, and the clinical effect of the steroids thereon is varied; the effect on the IV type (diffuse proliferation type) cannot be expected even by administering in a large amount, rather there is the possibility of aggravation.
An immunosuppressive agent is used in combination when therapy using only adrenocortical steroid is insufficient in the case of steroid-resistant and frequently relapsing nephrosis syndrome, rapidly progressive glomerulonephritis or lupus nephritis, or for the purpose of reducing the dose of the adrenocortical steroid. Generally used agents include cyclophosphamide, cyclosporin A and mizoribine. Cyclophosphamide is used frequently, but there occur various side effects depending on the dose. Major side effects include bone marrow inhibition, hepatic damage, alopecia, lung fibrosis, bleeding cystitis and hypofunction of sexual glands. Cyclosporin A shows an immunosuppressive action on T cells, but it has severe side effects include renal damage, hepatic damage, central nerve damage, infections and acute pancreatitis, among which the renal damage occurs depending on the blood concentration, thus making it necessary to monitor the blood concentration. Mizoribine has less side effects than other immunosuppressive agents, but is poor in effect on the diseases.
As described above, there are a large number of cases where the effects of the adrenocortical steroids used as the first choice in conventional therapy are not satisfactory, while the immunosuppressive agents used for compensating therefor have the problem of side effects.
2) Autoimmune Diseases in which Autoantibody is Involved
The autoantibody observed in autoimmune diseases is roughly divided into 2 groups depending on the characteristic distribution of its corresponding antigen in the body. The first group is an organ-specific autoantibody observed in organ-specific autoimmune diseases. This kind of autoantibody corresponds to anti-thyroid-stimulating hormone receptor antibody detected in patients with Basedow's disease, or to an anti-acetyl choline receptor antibody detected in patients with severe myasthenia. The second group is the one which reacts with antigen present in almost all organs in the body or in serum, and is called organ-unspecific autoantibody. The characteristic autoantibody in systematic autoimmune diseases such as glycogen storage disease is included in this group. These autoimmune antibodies directly damage organs or form an immune complex thereby generating the morbid state of autoimmune diseases. Further, even in autoimmune diseases wherein the relationship between the presence of autoantibody and the morbid state is not clear, the detection of autoantibody is revealed to be clinicall
Ishibashi Akira
Nagai Mitsuo
Tokuhara Naoki
Yamauchi Toshihiko
Eisai Co. Ltd.
Nixon & Vanderhye
Patel Sudhaker B.
Raymond Richard L.
LandOfFree
Retinoic acid agonists as preventive and therapeutic agents... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Retinoic acid agonists as preventive and therapeutic agents..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Retinoic acid agonists as preventive and therapeutic agents... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2865598