YC-6 Injection Solubilization via Hydroxypropyl-Beta-Cyclodextrin
Solution Overview
Problem
Current neuronprotective agents for Acute Ischemic Stroke, such as 5α-androstane-3β,5,6β-triol (YC-6), face solubility issues in water, leading to irritation from non-aqueous solvents and potential precipitation upon dilution, which limits their efficacy and safety for clinical use.
Innovation Solution
The use of hydroxypropyl-β-cyclodextrin as a solubilizing agent increases the solubility of YC-6, reducing solvent irritation and allowing its formulation into injectable forms like liquid or solid injections, sterile powders, and infusions, without causing adverse reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If non-aqueous solvents are used to increase YC-6 solubility, then solubility is improved, but irritation and precipitation occur
Solution Approach 1:
The patent uses hydroxypropyl-β-cyclodextrin as an intermediary substance to solubilize YC-6. The cyclodextrin forms an inclusion complex with YC-6, where the hydrophobic cavity of cyclodextrin accommodates the steroid molecule, enabling water solubility without using irritating non-aqueous solvents. This mediator approach resolves the contradiction by providing an alternative solubilization mechanism.
Solution Approach 2:
The invention creates a composite solubilization system combining hydroxypropyl-β-cyclodextrin with YC-6 in aqueous solution. This composite approach forms a stable inclusion complex that maintains YC-6 solubility while eliminating the need for harmful non-aqueous solvents, thus resolving the irritation issue while maintaining solubility enhancement.
2Quantity of substance
If non-aqueous solvents are used to increase YC-6 solubility, then solubility is improved, but precipitation occurs upon dilution
Solution Approach 1:
Hydroxypropyl-β-cyclodextrin acts as a stable intermediary that forms a robust inclusion complex with YC-6. This complex remains stable upon dilution with water because the host-guest interaction between cyclodextrin and YC-6 is maintained even at lower concentrations, preventing precipitation that occurs with non-aqueous solvent systems.
Solution Approach 2:
The invention changes the solubilization mechanism from relying on non-aqueous solvent properties to using cyclodextrin inclusion complexation. This parameter change in the solubilization approach ensures stability upon dilution, as the inclusion complex formation is not dependent on high solvent concentration and remains effective across a range of dilutions.
3Quantity of substance
If conventional solubilizing agents are used, then solubility is increased, but efficacy and safety are adversely affected
Solution Approach 1:
The patent employs hydroxypropyl-β-cyclodextrin as a biocompatible intermediary that enhances solubility without compromising efficacy or safety. Cyclodextrins are recognized as safe excipients with good biocompatibility, and the inclusion complex maintains YC-6's pharmacological activity while improving its solubility profile, thus resolving the reliability concern.
Solution Approach 2:
The invention changes the solubilizing agent from conventional potentially harmful substances to hydroxypropyl-β-cyclodextrin, which has favorable safety and efficacy profiles. This parameter change in the excipient selection maintains YC-6's therapeutic effects while improving safety, as cyclodextrins are well-tolerated and do not interfere with the drug's mechanism of action.
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
This approach enhances the solubility and safety of YC-6 injections, enabling effective intravenous administration without irritation, and simplifies the preparation process, making it suitable for urgent treatments while maintaining efficacy.
Implementation Method 1
YC-6 is insoluble in water. Although its solubility is increased in conventional non-aqueous solvents or mixtures thereof... The present invention uses hydroxypropyl-β-cyclodextrin as a solubilizing agent to prepare YC-6 injections
Data Source
AI summary
A 5α-androstane-3β,5,6β-triol injection and its preparation are disclosed. The injection uses hydroxypropyl-β-cyclodextrin as a solubilizing agent and the active ingredient is present in a part by weight ratio of 1-20:40-500 to the hydroxypropyl-β-cyclodextrin. The injection may also comprise 1∼100 parts of an isotonic adjusting agent, 0∼200 parts of a freeze drying filler, and 0∼2000 parts of a solvent. The preparation method comprises dissolving hydroxypropyl-β-cyclodextrin solution, 5α-androstane-3β,5,6β-triol and soluble excipients in water for injection in sequence to obtain a raw injection solution, and subjecting the raw injection solution to decolorization, depyrogenation, filtration and sterilization to obtain the injection. Drying the filtrate yields a solid for injection.