FK506 Derivatives for Cryptococcus and Candida Infections
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Solution Overview
Problem
Current antifungal agents are ineffective against fungal infections caused by Cryptococcus and Candida species, particularly in immunocompromised patients, due to toxicity, narrow spectrum of activity, and fungistatic nature, and there is a need for agents with broad-spectrum activity and improved pharmacological properties.
Innovation Solution
The use of FK506 derivatives, such as 31-O-demethyl-FK506, 9-deoxo-FK506, 9-deoxo-31-O-demethyl-FK506, and 9-deoxo-prolyl-FK506, as a pharmaceutical composition to treat fungal infections caused by Cryptococcus and Candida species, which exhibit antifungal activity without significant toxicity to the human body.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If azole-based compounds or amphotericin B are used as antifungal agents, then fungal infections can be treated, but severe side effects occur
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of FK506 to create derivatives with altered pharmacological properties. Specifically, the derivatives maintain immunosuppressive activity while gaining enhanced antifungal efficacy against Cryptococcus and Candida species, changing the efficacy parameter without proportionally increasing toxicity
Solution Approach 2:
The invention creates a composite pharmaceutical approach by combining FK506 derivatives with specific pharmacological profiles that integrate both immunosuppressive and antifungal activities. This composite action allows treatment of fungal infections in immunocompromised patients without the severe side effects of conventional antifungal agents
2Reliability
If current antifungal agents are used, then some fungal infections can be treated, but the spectrum of activity is narrow
Solution Approach 1:
The FK506 derivatives demonstrate multi-functionality by exhibiting broad-spectrum antifungal activity against multiple fungal genera including Cryptococcus, Candida, Aspergillus, and others. This universal activity profile allows a single agent to treat diverse fungal infections that previously required different specialized agents
3Reliability
If current antifungal agents are used, then fungal growth can be inhibited, but the agents are fungistatic rather than fungicidal
Solution Approach 1:
The patent applies parameter changes by modifying the pharmacological action of the FK506 derivatives to achieve fungicidal activity rather than merely fungistatic effects. The derivatives demonstrate concentration-dependent fungicidal activity, changing the fundamental mode of action parameter from growth inhibition to direct fungal cell killing
4Reliability
If FK506 derivatives are used at higher concentrations, then inhibitory activity increases, but potential toxicity may increase
Solution Approach 1:
The FK506 derivatives exhibit local quality differences in their pharmacological profile, showing selective toxicity toward fungal cells while maintaining safety for human cells. The derivatives demonstrate preferential accumulation or action in fungal cells, achieving high efficacy at concentrations that remain safe for human patients
Data Source
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AI summary
The present invention relates to a pharmaceutical composition containing FK506 derivative for treating a fungal infection caused by the genus Cryptococcus or the genus Candida, and a use thereof. In addition, the present invention relates to a therapeutic agent for fungal infection caused by the genus Cryptococcus or the genus Candida, the therapeutic agent containing FK506 derivative. The pharmaceutical composition of the present invention is harmless to the human body, and can make a great contribution to providing antifungal drugs with an excellent antifungal effect.