Sepiapterin Salt Forms for Stability and Bioavailability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for primary tetrahydrobiopterin deficiency (PBD) are varied and lack clinical evidence, and existing therapies for increasing tetrahydrobiopterin levels are not adequately effective or stable, leading to neuromotor deficits and neurotransmitter deficiencies.
Innovation Solution
Development of pharmaceutically acceptable salts of sepiapterin, such as nicotinate and tartrate salts, with improved stability, purity, and bioavailability, formulated with excipients and antioxidants to enhance tetrahydrobiopterin levels in the body.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oral administration of BH4 is used to treat PBD, then Phe concentrations are reduced, but the treatment lacks clinical evidence and stability
Solution Approach 1:
The patent changes the chemical form of sepiapterin from free base to pharmaceutically acceptable salt forms (e.g., hydrochloride, methanesulfonate, toluenesulfonate, benzenesulfonate, sulfate, phosphate, malonate, L-tartrate, fumarate, gentisate, glycolate, hydroxysuccinate, and oxalate salts). This parameter change improves stability, solubility, and bioavailability, providing a reliable treatment formulation with clinical potential.
2Reliability
If sepiapterin is administered to increase tetrahydrobiopterin levels, then neurotransmitter synthesis improves, but the compound lacks stability and purity
Solution Approach 1:
The patent transforms sepiapterin into salt forms with improved stability and purity characteristics. The salt formulations maintain structural integrity during storage and administration, preventing degradation while ensuring high purity levels suitable for pharmaceutical use.
Solution Approach 2:
The patent introduces pharmaceutically acceptable excipients and antioxidants as intermediary substances that protect sepiapterin from degradation during storage and administration. These excipients act as stabilizing agents, maintaining the integrity and purity of the active compound throughout the pharmaceutical formulation process.
3Quantity of substance
If current therapies are used to treat PBD, then treatment is provided, but exposure and bioavailability of sepiapterin are insufficient
Solution Approach 1:
The patent changes the pharmacokinetic parameters of sepiapterin by formulating it as salts with improved bioavailability. The salt forms enhance absorption, distribution, and metabolism characteristics, ensuring sufficient exposure and reliable delivery of sepiapterin to target tissues, thereby achieving adequate tetrahydrobiopterin levels.
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to new pharmaceutical salts and/or co-crystals of sepiapterin which exhibit improved properties. In particular, the invention relates to salts of sepiapterin with improved stability. The invention also relates to pharmaceutical compositions including a pharmaceutically effective amount of one or more salts and/or co-crystals of sepiapterin, as well as methods of treating tetrahydrobiopterin-related disorders including administration of a sepiapterin salt and/or co-crystal of the invention to a subject in need thereof.