Crystalline DEA-TTM Polymorph for Rapid Dissolution
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Solution Overview
Problem
Current tetrathiomolybdate compositions face challenges with poor solubility, slow dissolution rates, and excessive hydrogen sulfide release into the bloodstream, which complicates their use in treating acute conditions requiring rapid metabolic reduction, such as myocardial infarction and ischemia-reperfusion injuries.
Innovation Solution
A new polymorphic form of diethylamine tetrathiomolybdate (DEA-TTM) with specific XRPD patterns and thermal stability is developed, characterized by rapid dissolution in aqueous solutions and low hydrogen sulfide release, facilitating its use in pharmaceutical formulations for intravenous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional tetrathiomolybdate compositions are used, then therapeutic effect is achieved, but solubility is poor and dissolution rate is slow
Solution Approach 1:
The patent applies parameter changes by developing a new polymorphic form (Form I) of diethylamine tetrathiomolybdate with specific crystal structure parameters (space group P21, unit cell dimensions a=7.1433(4) Å, b=10.7328(5) Å, c=10.7485(8) Å). This polymorphic modification fundamentally changes the physical parameters of the compound, resulting in dramatically improved solubility (110 mg/ml in water at 25°C) and dissolution rate compared to conventional forms.
2Object-affected harmful factors
If conventional tetrathiomolybdate compositions are used, then therapeutic effect is achieved, but hydrogen sulfide release into bloodstream is excessive
Solution Approach 1:
The patent applies local quality by creating a polymorphic form with specific local crystal structure characteristics (hydrogen bonding patterns, molecular packing arrangement in space group P21) that selectively control the release properties. This localized structural modification results in reduced hydrogen sulfide release into the bloodstream while maintaining the therapeutic effect of metabolic reduction.
3Productivity
If rapid dissolution is achieved, then treatment effectiveness is improved, but hydrogen sulfide release may increase
Solution Approach 1:
The patent resolves this contradiction through parameter changes by establishing a specific polymorphic form with defined crystallographic parameters that simultaneously optimize multiple properties. Form I exhibits both rapid dissolution (complete dissolution in 1 minute) and reduced sulfide release, achieving a balanced profile that conventional forms cannot provide.
Data Source
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AI summary
The invention relates to a crystalline diethylamine tetrathiomolybdate salt (DEA-TTM). The invention also relates to methods for producing the crystalline DEA-TTM salt of the invention. The invention also relates to pharmaceutical compositions comprising the crystalline DEA-TTM salt of the invention. The invention also relates to the use of the crystalline DEA-TTM salt of the invention in the treatment of the human or animal body, in particular its use in treatment of a condition requiring reduced metabolism of an organ or the whole body of a patient, by administering to a patient in need thereof a therapeutically effective amount of the crystalline DEA-TTM salt.