Modified-Release Budesonide Composition for IgA Nephropathy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for IgA nephropathy, a progressive autoimmune kidney disease, are inadequate and often lead to significant side effects, with no approved therapy directly addressing the underlying cause, and existing immunosuppressive agents like corticosteroids have undesirable systemic side effects.
Innovation Solution
A budesonide formulation with a distinct in vitro release profile is administered locally to the distal ileum, targeting the production of pathogenic IgA antibodies, thereby reducing serum levels of BAFF and associated biomarkers without systemic effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic immunosuppressive agents like corticosteroids are used to treat IgA nephropathy, then disease progression is slowed, but significant systemic side effects occur
Solution Approach 1:
The invention segments the treatment approach by using a multi-layered capsule system that releases budesonide at different locations along the gastrointestinal tract. The first layer releases in the proximal small intestine and the second layer releases in the distal ileum, allowing localized treatment of Peyer's patches without systemic exposure to high doses of corticosteroids
Solution Approach 2:
The invention applies local quality by concentrating the immunosuppressive effect specifically at Peyer's patches in the distal ileum where pathogenic IgA is produced. The enteric-coated capsule ensures drug release occurs only in the distal ileum (pH > 7.0), delivering high local concentration of budesonide exactly where needed while minimizing systemic side effects
2Stability of the object's composition
If no approved therapy is used for IgA nephropathy, then patients maintain current kidney function, but disease progresses to end-stage renal disease
Solution Approach 1:
The invention takes preliminary action by targeting and suppressing pathogenic IgA production at its source (Peyer's patches) before immune complexes can form and deposit in the kidneys. By using enteric-coated budesonide that releases in the distal ileum, the treatment prevents the formation of galactose-deficient IgA1 and subsequent immune complex deposition, thereby preventing kidney damage before it occurs
Solution Approach 2:
The invention uses enteric-coated capsules as an intermediary delivery system that transports budesonide through the gastrointestinal tract without premature release. The coating acts as a mediator that ensures the drug reaches the distal ileum (pH > 7.0) where it can selectively suppress pathogenic IgA production in Peyer's patches, thereby preventing downstream kidney damage
3Object-affected harmful factors
If antihypertensive medications are used to manage IgA nephropathy symptoms, then blood pressure and proteinuria are reduced, but the underlying cause is not addressed
Solution Approach 1:
The invention extracts and treats the root cause of IgA nephropathy by specifically targeting Peyer's patches in the distal ileum where pathogenic galactose-deficient IgA1 is produced. By using enteric-coated budesonide that releases at pH > 7.0, the treatment removes the source of pathogenic antibodies before they can enter circulation and damage kidneys, rather than merely managing symptoms like hypertension and proteinuria
Data Source
AI summary
The present invention provides for a method of treatment of IgA nephropathy, which method comprises:(i) identifying a pharmaceutically acceptable composition intended to treat IgA nephropathy comprising budesonide and one or more pharmaceutically-acceptable excipients that provide for a modified release of said budesonide after administration to the gastrointestinal tract, which composition fulfils the following requirements in a standard in vitro USP<711>/Ph.Eur. 2.9.3 dissolution test using a dissolution apparatus according to Apparatus 2 (Paddle Apparatus) of said test;(a) the composition fulfils the requirement that no more than about 10% of the budesonide is released into the dissolution medium within about 120 minutes, when the dissolution medium is aqueous and has a pH of about 1.2;(b) the composition fulfils the requirement that no more than about 10% of the budesonide is released into a pharmaceutically-relevant dissolution medium within about 30 minutes; and(c) the composition fulfils the requirement that at least about 70% of the budesonide is released into the pharmaceutically-relevant dissolution medium within about 120 minutes;(ii) wherein the method comprises the step of administering said composition to a patient with IgA nephropathy in need of said treatment.