Biopterin Derivative Solid Formulations for Oxidation Stability
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Solution Overview
Problem
Biopterin derivatives, such as 4-Amino-5,6,7,8-tetrahydro-L-biopterin and 4-Amino-7,8-dihydro-L-biopterin, are sensitive to oxidation when formulated in liquid solutions, making them unsuitable for long-term storage and medical treatment applications.
Innovation Solution
A solid pharmaceutical composition comprising biopterin derivatives, such as compounds (I) and (II), combined with phosphate salts like Na2HPO4·2H2O and NaH2PO4·2H2O, and optionally NaCl, is developed for intravenous administration, ensuring stability and ease of use by forming a ready-to-use solution upon mixing with a pharmaceutically acceptable carrier.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If biopterin derivatives are formulated in liquid solutions, then they are suitable for intravenous administration, but they are sensitive to oxidation and unsuitable for long-term storage
Solution Approach 1:
The patent changes the physical state parameter of the biopterin derivative from liquid to solid form. This parameter change fundamentally resolves the contradiction by allowing the substance to be stable in solid form for storage, while still enabling intravenous administration through reconstitution with a carrier fluid before use.
Solution Approach 2:
The patent segments the administration process into two distinct stages: (1) storage as a stable solid composition, and (2) reconstitution with a pharmaceutically acceptable carrier immediately before intravenous administration. This segmentation allows each stage to optimize for its specific requirement—stability during storage and ease of administration during use.
2Stability of the object's composition
If biopterin derivatives are provided in solid form, then they are stable against oxidation, but they require mixing with a carrier for intravenous administration
Solution Approach 1:
The patent performs preliminary action by pre-formulating the biopterin derivative with the carrier fluid components in a solid composition that is designed to be easily reconstituted. This preliminary preparation ensures that when the solid is mixed with the carrier, the resulting solution is immediately suitable for intravenous administration without requiring complex additional processing steps.
Data Source
AI summary
Disclosed is a method of preparing a solution adapted for administration by infusion, comprisinga) a compound having the formula (I):and/or a compound having the formula (II):andb) two different sodium phosphate salts, wherein the two different sodium phosphate salts are NaH2PO4·2H2O and Na2HPO4·2H2O, and wherein the quantity of the NaH2PO4·2H2O and Na2HPO4·2H2O present in the composition is chosen such that the molar ratio of both NaH2PO4·H2O and Na2HPO4·2H2O to compound (I) or compound (II) ranges from 0.02 to 0.5 and optionally NaCl. Also disclosed is a method of treating a disease in a subject, comprising the step of administering to a subject in need thereof a reconstituted solution as disclosed.