Controlled-Release PTH Dosing for Stable Serum Calcium
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Solution Overview
Problem
Current therapies for hypoparathyroidism, such as oral calcium and active vitamin D supplementation, are associated with marked swings in blood Ca2+, hypercalciuria, kidney stones, nephrocalcinosis, and ectopic calcification, and do not effectively manage calcium and phosphate levels, leading to hypercalcemia, hypocalcemia, and hypercalciuria, while continuous PTH therapies are inconvenient and risky.
Innovation Solution
A controlled-release PTH compound is administered intermittently, preferably daily or weekly, to maintain stable serum calcium levels and reduce side effects, using a pharmaceutical composition that includes a controlled-release PTH compound or its pharmaceutically acceptable salts, hydrates, or solvates, administered via subcutaneous injection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If controlled-release PTH compounds are administered frequently (e.g., every 8 hours) to maintain stable serum calcium levels, then serum calcium stability is improved, but patient compliance and quality of life deteriorate due to the burden of frequent injections
Solution Approach 1:
The patent implements periodic action by administering controlled-release PTH compounds at extended intervals (once every 24 hours or less frequently) rather than continuously every 8 hours. The controlled-release formulation maintains stable serum calcium levels throughout the extended dosing interval, achieving both calcium stability and improved patient compliance through reduced injection frequency.
2Reliability
If the dosage of controlled-release PTH compound is increased to match the molar equivalent of immediate-release PTH 1-84, then therapeutic effect is improved, but risk of hypercalcemia and adverse events increases
Solution Approach 1:
The patent applies parameter changes by adjusting the dosage of controlled-release PTH compounds to be lower than the molar equivalent dose of immediate-release PTH 1-84. This dosage reduction, combined with the controlled-release mechanism, maintains therapeutic efficacy while preventing hypercalcemia and reducing adverse events associated with higher dosages.
3Speed
If immediate-release PTH 1-84 is administered to achieve rapid therapeutic effect, then onset of action is improved, but serum calcium fluctuations and adverse events increase
Solution Approach 1:
The patent implements continuity of useful action through controlled-release formulations that provide sustained, steady delivery of PTH compounds over extended periods. This continuous release mechanism maintains stable serum calcium levels without the peaks and troughs associated with immediate-release formulations, eliminating the need for frequent dosing while preventing hypercalcemia and other adverse events.
Data Source
AI summary
The present invention relates to a pharmaceutical composition comprising at least one controlled-release PTH compound or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment, control, delay or prevention of a condition that can be treated, controlled, delayed or prevented with PTH, pharmaceutical composition comprising at least one controlled-release PTH compound or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment, control, delay or prevention of a condition that can be treated, controlled, delayed or prevented with PTH, wherein said pharmaceutical composition is administered no more frequent than once every 24 hours with a dosage of the controlled-release PTH compound that corresponds to no more than 70% of the molar equivalent dose of PTH 1-84 administered every 24 hours required to maintain serum calcium within normal levels over said 24 hour period in humans.