Anhydrous Sodium Thiosulfate Formulation for Pediatric Ototoxicity
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Solution Overview
Problem
Platinum-based chemotherapeutics cause irreversible and progressive hearing loss in pediatric patients, which significantly impacts their cognitive, psychosocial, and speech development, necessitating a safe and effective pharmaceutical composition to reduce ototoxicity without compromising treatment efficacy.
Innovation Solution
Anhydrous sodium thiosulfate is synthesized and formulated into pharmaceutical compositions, characterized by specific X-ray powder diffraction patterns and purity criteria, and administered to pediatric patients following platinum-based chemotherapy to mitigate ototoxicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If platinum-based chemotherapeutics are administered to treat pediatric malignancies, then cancer treatment efficacy is improved, but ototoxicity and hearing loss occur
Solution Approach 1:
Sodium thiosulfate acts as an intermediary protective agent that binds to platinum compounds, forming a protective complex that reduces the direct interaction between platinum and cochlear hair cells. This mediator approach allows platinum-based chemotherapy to maintain its anti-cancer efficacy while the thiosulfate prevents the harmful ototoxic effects.
Solution Approach 2:
The patent converts the harmful platinum compound into a beneficial form by having it react with sodium thiosulfate to form a protective complex. The platinum, which would normally be toxic to hearing, is transformed into a less harmful platinum-thiosulfate complex that can still treat cancer but no longer causes severe ototoxicity.
2Object-affected harmful factors
If conventional sodium thiosulfate pentahydrate is used, then ototoxicity reduction is achieved, but manufacturing complexity and purity issues arise
Solution Approach 1:
The patent changes the physical state parameter of sodium thiosulfate from the common pentahydrate form to the anhydrous form. This parameter change simplifies the manufacturing process by eliminating water removal steps and improves purity by avoiding hydration-related impurities, while maintaining the same ototoxicity reduction efficacy.
Solution Approach 2:
The patent extracts and removes the water of hydration from the sodium thiosulfate structure, transitioning from the pentahydrate form to the anhydrous form. This extraction of water simplifies the chemical structure, reduces manufacturing complexity, and improves the purity of the active ingredient without compromising its protective function.
3Manufacturing precision
If anhydrous sodium thiosulfate is synthesized, then purity and manufacturing simplicity are improved, but synthesis process complexity increases
Solution Approach 1:
The patent employs parameter changes in the synthesis process, specifically controlling temperature and reactant ratios to directly produce the anhydrous form. By adjusting these parameters, the synthesis pathway is simplified to avoid multiple purification steps, achieving high purity with reduced process complexity.
Solution Approach 2:
The patent performs preliminary action by designing the synthesis process to directly yield the anhydrous form from the start, rather than requiring subsequent dehydration steps. This preliminary planning of the synthesis pathway eliminates complex purification operations and streamlines the manufacturing process.
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 anhydrous sodium thiosulfate compositions effectively reduce the incidence and severity of ototoxicity in pediatric patients, preserving the efficacy of platinum-based treatments and minimizing adverse effects.
Implementation Method 1
Sodium thiosulfate has been used to reduce the nephrotoxicity and ototoxicity of cisplatin and other platinum-based chemotherapeutics. The mechanism of action involves the binding of thiosulfate to the platinum compound, forming a protective complex.
Implementation Method 2
a differential scanning calorimetry melting onset of about 331° C.
Implementation Method 3
an onset of decomposition at 436° C.
Data Source
AI summary
Described herein is anhydrous sodium thiosulfate, methods for synthesizing anhydrous sodium thiosulfate, pharmaceutical compositions thereof, and methods of treating ototoxicity. Anhydrous sodium thiosulfate is synthesized from sodium sulfite, sulfur, and cetylpyridinium chloride. The anhydrous sodium thiosulfate is formulated into a pharmaceutical composition comprising a buffer and solvent. These compositions are useful for eliminating or reducing ototoxicity in pediatric patients receiving platinum-based chemotherapeutics.