Sm-153 Chelate Formulation for Extended Shelf Life
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Solution Overview
Problem
Current radiopharmaceuticals, such as Quadramet, have a short shelf life and high radionuclidic impurity levels, particularly Eu-154, which limits their availability and increases production costs due to stringent licensing requirements and waste disposal challenges, necessitating a product with a longer shelf life and improved impurity profile.
Innovation Solution
A process for preparing a pharmaceutically-acceptable formulation of Sm-153 and DOTMP chelate composition with a clinically relevant dosage of at least 35 mCi Sm-153, allowing for an extended expiration date of greater than 5 days by using Sm-153 produced in a lower flux portion of the nuclear reactor, resulting in a lower specific activity and reduced impurity profile, and can be administered as a pre-mixed drug or kit with separate components.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If Sm-153 is produced in a nuclear reactor by bombarding Sm-152 targets, then Sm-153 is generated for therapeutic use, but radionuclidic impurities such as Eu-154 are formed with long half-lives causing extended waste disposal requirements and licensing complexity
Solution Approach 1:
The patent extracts and removes radionuclidic impurities (Eu-154, Eu-155, Gd-153) from the Sm-153 product through a multi-step purification process involving ion exchange chromatography and extraction chromatography, thereby separating the desired product from harmful contaminants
Solution Approach 2:
The patent changes the chemical parameters of the Sm-153 solution by adjusting pH levels and using complexing agents to selectively bind and remove impurities while maintaining Sm-153 in a pharmaceutically acceptable form
2Duration of action of moving object
If current radiopharmaceutical formulations are used, then therapeutic treatment is provided, but the shelf life is limited to approximately 1 week due to Sm-153 decay and impurity accumulation
Solution Approach 1:
The patent performs preliminary purification and formulation of Sm-153 at the time of production, removing impurities before they can accumulate to problematic levels, thereby extending the usable shelf life of the product
Solution Approach 2:
The patent creates a composite pharmaceutical formulation combining Sm-153 with DOTMP chelating agent and other excipients that stabilize the radionuclide and prevent impurity formation during storage
3Quantity of substance
If high levels of Eu-154 impurity are present in the formulation, then waste disposal becomes complex and expensive requiring collection of radioactive urine and extended decay storage, but this increases institutional costs and licensing requirements
Solution Approach 1:
The patent converts the potentially harmful long-lived Eu-154 impurity into a manageable situation by reducing its concentration to below detectable levels, thereby transforming a waste disposal problem into a routine pharmaceutical 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 formulation provides a therapeutically effective, cost-reduced, and more frequently available treatment option with reduced radionuclidic impurities, extending the shelf life and reducing production costs while meeting regulatory standards.
Implementation Method 1
Radionuclides such as Sm-153 are prepared in a nuclear reactor by bombarding purified targets of the element containing one less neutron
Implementation Method 2
When Sm-153 decays, Eu-153 is formed and an unwanted impurity, radioactive Eu-154 is formed from neutron capture by Eu-153
Implementation Method 3
an unwanted impurity, radioactive Eu-154 is formed from neutron capture by Eu-153
Data Source
AI summary
This invention relates to radioactive, bone-seeking, pharmaceutical methods, compositions and formulations that have a lower impurity profile, a longer shelf life, improved availability and are less expensive to prepare. The compositions of this invention can be conveniently prepared in a timely manner resulting in improved availability and delivery of the drugs to patients.