BK B2 Receptor Antagonist Matrix Tablet for Sustained Release
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Solution Overview
Problem
Existing bradykinin B2 receptor antagonists, such as those with a chemical structure according to Formula (1), face challenges including low metabolic stability, low bioavailability, formation of glutathione adducts, bioactivation, and poor aqueous solubility, limiting their utility as effective therapeutic agents for chronic diseases.
Innovation Solution
Formulating a BK B2 receptor antagonist with a chemical structure according to Formula (1) into an extended-release composition, particularly a matrix tablet with a hydrophilic matrix-forming polymer, to provide sustained release over at least 10 hours, enhancing absorption from the gastrointestinal tract, especially the colon, and allowing once-daily or twice-daily dosing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If compounds of Formula (1) are used as BK B2 receptor antagonists, then pharmacological activity and tolerability are improved, but aqueous solubility deteriorates
Solution Approach 1:
The patent changes the physical state parameters of the compound by formulating it as a solid dispersion in a carrier polymer, transforming it from a poorly soluble crystalline form to an amorphous dispersed state that enhances aqueous solubility while maintaining pharmacological activity
Solution Approach 2:
The patent creates a composite material system combining the BK B2 receptor antagonist of Formula (1) with a carrier polymer to form a solid dispersion, where the polymer matrix improves the solubility and bioavailability of the active compound without compromising its receptor-blocking activity
2Speed
If conventional dosing formulations are used, then immediate effect is achieved, but patient compliance for chronic treatment deteriorates
Solution Approach 1:
The patent segments the dosing schedule by providing an extended-release formulation that divides the daily dose into a single administration that releases medication progressively over 24 hours, replacing multiple daily doses with once-daily dosing to improve patient compliance
Solution Approach 2:
The patent ensures continuity of therapeutic action by designing an extended-release formulation that maintains effective plasma concentrations of the BK B2 receptor antagonist throughout the 24-hour dosing interval, preventing symptom recurrence and ensuring consistent disease control
3Ease of operation
If extended-release formulation is developed, then patient compliance is improved, but formulation complexity increases
Solution Approach 1:
The patent introduces a carrier polymer as an intermediary substance that facilitates the extended-release formulation, where the polymer serves as a biodegradable matrix that controls drug release kinetics without requiring complex mechanical or chemical delivery systems
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
The extended-release formulation ensures sustained therapeutic efficacy with improved patient compliance and tolerability by maintaining effective plasma levels for chronic conditions like angioedema, overcoming the limitations of previous compounds.
Implementation Method 1
a matrix tablet that is adapted to release the BK B2 receptor antagonist over a period of at least 10 hours
Implementation Method 2
The matrix tablet may be designed to provide for the extended-release of the incorporated BK B2 receptor antagonist
Data Source
AI summary
The invention relates to the treatment of diseases or conditions that are responsive to bradykinin BK B2 receptor modulation. The treatment is preferably a prophylactic and/or chronic treatment and comprises the oral administration of a BK B2 receptor antagonist according to Formula (1), or a salt or solvate thereof, wherein R is deuterium or hydrogen: such as (S)-./V-(1-deutero-1-(3-chloro-5-fluoro-2-((2-methyl-4-(1-methyl-1/f-1,2,4-triazol-5-yl)quinolin-8-yloxy)methyl)phenyl)ethyl)-2-(difluoromethoxy)acetamide, by means of an extended-release composition that is adapted to release the BK B2 receptor antagonist over a period of at least 10 hours.