Budesonide Modified-Release Composition for IgA Nephropathy
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Solution Overview
Problem
Current treatments for IgA nephropathy, a progressive autoimmune kidney disease, are inadequate and often associated with significant side effects, and there is a need for a targeted, locally-acting immunosuppressive agent that can effectively reduce the formation of pathogenic IgA antibodies without systemic exposure.
Innovation Solution
A budesonide formulation with a specific in vitro release profile is administered to the gastrointestinal tract, particularly the distal ileum, to selectively target and reduce serum levels of BAFF and pathogenic IgA antibodies, minimizing systemic side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic immunosuppressive agents are used to treat IgA nephropathy, then disease progression can be controlled, but significant side effects occur
Solution Approach 1:
The patent segments the immunosuppressive therapy by using multiple dosage forms with different release profiles (immediate-release and modified-release formulations) to deliver the drug to different locations in the gastrointestinal tract, thereby achieving localized treatment at the site of IgA antibody production while minimizing systemic exposure and side effects
Solution Approach 2:
The patent applies local quality by designing formulations that release budesonide specifically in the ileum where Peyer's patches are located, creating high local drug concentration at the target site while maintaining low systemic levels, thus effectively treating the underlying cause of IgA nephropathy without the harmful systemic effects associated with conventional systemic immunosuppression
2Object-affected harmful factors
If antihypertensive medications are used to manage IgA nephropathy symptoms, then blood pressure and proteinuria can be reduced, but the underlying cause is not addressed
Solution Approach 1:
The patent applies preliminary action by targeting and treating the underlying cause of IgA nephropathy (aberrant IgA antibody production in Peyer's patches) before it progresses to cause significant kidney damage and hypertension, using budesonide formulations that act on the root cause rather than merely managing downstream symptoms
3Reliability
If budesonide is administered to reduce pathogenic IgA antibodies, then serum levels of BAFF and IgA antibodies decrease, but systemic exposure may still occur
Solution Approach 1:
The patent applies dynamics by using modified-release formulations that control the temporal and spatial release of budesonide, creating a dynamic delivery system that releases the drug progressively as it travels through the gastrointestinal tract, ensuring sustained local action at the ileum while minimizing premature systemic absorption
Solution Approach 2:
The patent uses the gastrointestinal tract itself as an intermediary delivery system, leveraging the natural passage of the drug through the GI tract to deliver budesonide to the target site (ileum with Peyer's patches) while the formulation characteristics control where and how the drug is released, thereby reducing direct systemic exposure
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.