Prodrug CPHPC Derivative for Oral SAP Depletion
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Solution Overview
Problem
Current treatments for amyloidosis and related conditions, such as Alzheimer's disease and type 2 diabetes, face challenges in completely removing serum amyloid P component (SAP) from amyloid deposits, leading to incomplete regression of amyloid and ongoing disease progression, and existing compounds like CPHPC have low oral bioavailability and cause discomfort with long-term administration.
Innovation Solution
The compound (2R,2'R)-bis(((tetrahydro-2H-pyran-4-carbonyl)oxy)methyl) 1,1'-adipoylbis(pyrrolidine-2-carboxylate) is developed, which exhibits good physicochemical properties, including oral bioavailability and stability, capable of generating CPHPC, allowing for efficient SAP depletion without the drawbacks of existing treatments.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing compounds like CPHPC are used for SAP depletion, then SAP can be depleted from circulation, but oral bioavailability is low and long-term administration causes discomfort
Solution Approach 1:
The patent applies preliminary action by developing a prodrug formulation of CPHPC that is prepared in advance with improved physicochemical properties. The prodrug is designed to be orally bioavailable and stable in the gastrointestinal tract, converting to active CPHPC in vivo. This preliminary preparation resolves the contradiction by enabling oral administration (improving ease of operation) while maintaining SAP depletion efficacy (maintaining reliability).
Solution Approach 2:
The patent applies parameter changes by modifying the chemical structure of CPHPC to create a prodrug with altered physical and chemical parameters. The prodrug formulation changes solubility, stability, and bioavailability parameters, allowing oral administration while maintaining the core SAP-depleting function. This resolves the contradiction between oral bioavailability and treatment efficacy.
2Productivity
If palindromic bivalent ligands are administered for SAP depletion, then rapid and almost complete depletion of SAP from circulation is achieved, but not all SAP bound to amyloid deposits is removed
Solution Approach 1:
The patent applies continuity of useful action by designing a treatment regimen where the prodrug formulation enables sustained oral administration. The continuous supply of active CPHPC through oral dosing maintains SAP depletion in circulation over time, which progressively leads to complete amyford deposit regression. This continuous action resolves the contradiction between rapid initial depletion and complete eventual removal.
Solution Approach 2:
The prodrug formulation performs preliminary action by ensuring stable delivery and absorption of CPHPC precursors in the gastrointestinal tract. This preliminary optimized delivery system ensures continuous availability of active compound, enabling both rapid initial SAP depletion and sustained action for complete amyford deposit removal over time.
3Reliability
If long-term administration of CPHPC is required for complete amyford regression, then treatment duration increases, but patient comfort and compliance decrease due to administration discomfort
Solution Approach 1:
The patent applies the intermediary principle by introducing a prodrug formulation as a mediator between the patient and active CPHPC. The prodrug serves as an intermediate vehicle that is orally bioavailable and comfortable to administer, which then converts to active CPHPC in the body. This intermediary resolves the contradiction by making long-term treatment comfortable and compliant while maintaining efficacy for complete amyford regression.
Solution Approach 2:
The patent applies parameter changes by modifying CPHPC into a prodrug with improved physical and chemical parameters for oral administration. The prodrug formulation changes solubility, stability, and bioavailability parameters, enabling comfortable long-term oral dosing while maintaining the therapeutic effect needed for complete amyford regression over time.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This compound effectively depletes SAP, facilitating the removal of amyloid deposits and improving treatment outcomes for amyloidosis, Alzheimer's disease, and type 2 diabetes, while offering a more tolerable and efficient administration method compared to existing therapies.
Implementation Method 1
The compound (2R,2'R)-bis(((tetrahydro-2H-pyran-4-carbonyl)oxy)methyl) 1,1'-adipoylbis(pyrrolidine-2-carboxylate) is developed, which exhibits good physicochemical properties, including oral bioavailability and stability, capable of generating CPHPC
Data Source
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AI summary
The present invention relates to the compound ((2R,2'R)-bis(((tetrahydro-2H-pyran-4- carbonyl)oxy)methyl) 1,1'-adipoylbis(pyrrolidine-2-carboxylate), pharmaceutical compositions comprising the same and the use of the same for treatment of diseases or disorders wherein depletion of serum amyloid P component (SAP) would be beneficial, including amyloidosis, Alzheimer s disease, type 2 diabetes mellitus and osteoarthritis.