Cyclodextrin Complex for 5-FU Solubility at Physiological pH
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Solution Overview
Problem
Current chemotherapy methods using 5-fluorouracil (5-FU) and folinic acid face challenges such as severe vein damage and precipitation issues at physiologically unacceptable pH levels, limiting their effective co-administration and synergistic effect in cancer treatment.
Innovation Solution
A composition comprising 5-FU, folinic acid, and cyclodextrin, which forms a non-covalent complex to maintain 5-FU in solution at physiological pH, preventing precipitation and allowing simultaneous administration, thereby minimizing side effects and enhancing treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If 5-FU is administered at pH 9 to achieve therapeutic effect, then anti-cancer activity is improved, but severe vein damage and phlebitis occur
Solution Approach 1:
Cyclodextrin acts as a mediator between 5-FU and the aqueous environment, forming an inclusion complex that enables 5-FU to be administered at physiological pH without precipitation, thereby eliminating vein damage while maintaining therapeutic efficacy
Solution Approach 2:
The invention changes the pH parameter from 9 (therapeutic but harmful) to physiological pH 6.5-7.5 (safe but previously ineffective due to precipitation), using cyclodextrin complexation to maintain 5-FU solubility across this pH transition
2Stability of the object's composition
If 5-FU and folinic acid are administered in separate injections to avoid precipitation, then solution stability is improved, but synergistic effect is not realised
Solution Approach 1:
The invention merges two previously separate administrations (5-FU and folinic acid) into a single combined formulation, enabling simultaneous delivery while maintaining solution stability through cyclodextrin-mediated solubility enhancement
Solution Approach 2:
Cyclodextrin serves as an intermediary that enables the co-solubilization of both 5-FU and folinic acid in the same aqueous solution at physiological pH, allowing their synergistic interaction without precipitation
3Reliability
If 5-FU concentration is increased to achieve therapeutic effect, then anti-cancer potency is improved, but precipitation occurs at physiological pH
Solution Approach 1:
Cyclodextrin molecules act as intermediaries that encapsulate 5-FU molecules through non-covalent interactions, enabling high concentrations of 5-FU (1-50 mg/ml) to remain solubilized in aqueous solution at physiological pH without precipitation
Solution Approach 2:
The formulation creates a composite system where cyclodextrin and 5-FU form an inclusion complex, combining the solubility advantages of cyclodextrin with the therapeutic potency of high-concentration 5-FU
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 cyclodextrin-based composition enables the simultaneous administration of 5-FU and folinic acid at physiologically acceptable pH, reducing side effects, improving delivery, and potentially simplifying administration, while maintaining therapeutic effectiveness against various cancers.
Implementation Method 1
The cyclodextrin (CD) or salt or derivative thereof may be present in a concentration sufficient to prevent the 5-FU or salt or analogue thereof from precipitating out of solution
Implementation Method 2
The 5-FU and cyclodextrin may be present in the composition in the form of a non-covalent complex, i.e. the 5-FU may be complexed to the cyclodextrin but not covalently bound thereto
Data Source
AI summary
The present invention relates to compositions comprising 5-fluorouracil, or a pharmaceutically acceptable salt or analogue thereof, folinic acid, or a pharmaceutically acceptable salt thereof and a cyclodextrin, or a pharmaceutically acceptable salt or derivative thereof. The invention also relates to methods for the treatment of cancer using such compositions.