Branched Hetero Polyoxyalkylene Compound for Stable Drug Modification
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Solution Overview
Problem
Existing polyoxyalkylene derivatives face challenges such as instability due to prone hydrolysis of bonds, difficulty in achieving homogeneity due to asymmetric carbons, and issues with introducing different biofunctional molecules, leading to impurities and complex drug design.
Innovation Solution
A novel branched hetero polyfunctional polyoxyalkylene compound with stable ether bonds and no asymmetric carbon in the core skeleton, featuring different reactive functional groups at terminal ends, allowing for controlled polymerization and reduced impurities, facilitating the modification of bio-related substances.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If polyoxyalkylene derivatives are used to modify drugs to improve circulation in blood, then the circulation time is extended, but the bonds are prone to hydrolysis during storage or under alkaline conditions, leading to dissociation of the polyoxyalkylene chain
Solution Approach 1:
The patent changes the chemical bond type from amide/carbamate/ester bonds to ether bonds in the polyoxyalkylene derivative. This parameter change in bond chemistry fundamentally improves stability while maintaining the circulation-time extension function, as ether bonds are resistant to hydrolysis under physiological and storage conditions.
Solution Approach 2:
The patent creates a composite structure combining polyoxyalkylene chains with a core skeleton compound through stable ether bonds. This composite approach maintains the beneficial circulation properties while the ether bond linkage provides hydrolytic stability, resolving the contradiction between duration of action and reliability.
2Ease of manufacture
If core skeleton compounds with asymmetric carbons are used in polyoxyalkylene derivatives, then the compounds can be synthesized, but the compounds are not homogeneous when bonding to drugs, complicating development as medicaments
Solution Approach 1:
The patent deliberately uses a symmetric core skeleton compound (pentaerythritol or dipentaerythritol) instead of asymmetric ones. This symmetry ensures that all polyoxyalkylene chains are equivalent, producing homogeneous derivatives that bond uniformly to drugs, thereby resolving the homogeneity problem while maintaining ease of manufacture.
Solution Approach 2:
The patent employs a symmetric core structure with multiple equivalent hydroxyl groups, ensuring that all resulting polyoxyalkylene chains are identical. This homogeneity in structure leads to consistent drug-bonding behavior and uniform pharmacological properties, eliminating the homogeneity issues associated with asymmetric carbons.
3Ease of manufacture
If stepwise reaction methods are used to introduce polyoxyalkylene chains, then the compounds can be synthesized, but impurities with different numbers of polyoxyalkylene chains are formed, making purification difficult
Solution Approach 1:
The patent uses a pre-formed core skeleton compound with all hydroxyl groups protected or prepared for simultaneous reaction. This preliminary preparation allows all polyoxyalkylene chains to be introduced in a single step, eliminating the stepwise reactions that generate impurities with varying chain lengths, thus achieving high purity without complicating purification.
Solution Approach 2:
The patent segments the synthesis approach by using a discrete core skeleton compound as a starting point, rather than building chains stepwise. This segmentation allows controlled, simultaneous attachment of multiple polyoxyalkylene chains in one reaction, producing a pure product with defined structure and eliminating the need for complex purification of polymeric impurities.
4Device complexity
If mono-functional polyoxyalkylene derivatives are used, then the structure is simple, but the ability to introduce different biofunctional molecules at terminal ends is limited
Solution Approach 1:
The patent creates a universal core skeleton compound with multiple equivalent reactive sites (four hydroxyl groups in pentaerythritol or dipentaerythritol). This multi-functional core can simultaneously or sequentially bond to different types of biofunctional molecules at each terminal end, providing versatility while maintaining a relatively simple overall structure based on the symmetric core.
Data Source
AI summary
A branched hetero polyfunctional polyoxyalkylene compound represented by the following formula (1):wherein Z represents a hydroxyl group-removed residue of pentaerythritol or dipentaerythritol, OA1 and OA2 represent an oxyalkylene group having 2 to 4 carbon atoms, L1, L2 and L3 represent an alkylene group or an alkylene group that contains an ester bond, a urethane bond, an amide bond, an ether bond, a carbonate bond, a secondary amino group or a urea bond, X and Y are different from each other and represent a functional group capable of a chemical reaction; m and n are an average number of moles of the oxyalkylene group added, m represents 5 to 1,000, n represents 0 to 1,000, and p, q and r represent 0 or 1; and s1 is an integer of 2 or more and s1+s2=4 or 6.