Leuprolide Extended-Release Depot for Sustained Ovarian Suppression
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for hormone receptor-positive (HR-positive) breast cancer in pre/perimenopausal patients fail to consistently achieve ovarian function suppression over an extended period, necessitating a more effective drug formulation for concurrent use with adjuvant endocrine therapies.
Innovation Solution
Administration of a flowable, extended-release composition comprising leuprolide or a pharmaceutically acceptable salt and a biodegradable polymer, such as poly(lactide-co-glycolide) copolymer, which forms an in situ depot upon injection, providing sustained release of leuprolide for ovarian function suppression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional GnRH agonists are used to suppress ovarian function, then ovarian suppression is achieved initially, but suppression is not maintained consistently over extended periods
Solution Approach 1:
The patent applies preliminary action by formulating leuprolide with biodegradable polymers (PLGA, PCL) and organic solvents (NMP, DMSO) to create a pre-designed extended-release system. The composition is prepared in advance with specific polymer-to-drug ratios and solvent content to ensure controlled dissolution and sustained release over 3-6 months, addressing the inconsistency of conventional formulations before treatment begins
Solution Approach 2:
The patent changes physical and chemical parameters by modifying the formulation composition (polymer type, molecular weight, crystallinity), solvent content (5-50% v/v), and processing conditions (lyophilization, sterilization). These parameter changes transform the drug delivery system to achieve consistent ovarian suppression for extended periods, resolving the reliability-duration contradiction
2Reliability
If adjuvant endocrine therapies are administered concurrently, then treatment efficacy is enhanced, but the need for reliable extended ovarian suppression becomes more critical
Solution Approach 1:
The patent employs composite materials by combining leuprolide with biodegradable polymers (PLGA, PCL) and organic solvents to create a multifunctional formulation. This composite approach integrates sustained release capability, sterility, and stability in a single system, enabling reliable ovarian suppression to enhance adjuvant endocrine therapy without proportionally increasing complexity
Solution Approach 2:
The organic solvent (NMP, DMSO) acts as an intermediary by facilitating uniform drug distribution within the polymer matrix and enabling controlled dissolution in physiological conditions. This intermediary mechanism ensures consistent drug release kinetics, maintaining reliable ovarian suppression while simplifying the overall formulation structure for clinical use
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 extended-release composition effectively reduces estradiol and follicle-stimulating hormone levels to postmenopausal levels, enhancing the efficacy of adjuvant therapies by maintaining ovarian function suppression for up to 3 months, thereby reducing estrogen levels and supporting HR-positive breast cancer treatment.
Implementation Method 1
a biodegradable polymer to the HR-positive breast cancer patient in need of such treatment. Upon injection of the flowable, extended release composition into the subject and contact with bodily fluid, the organic solvent in the flowable, extended release composition dissipates and an in situ solid or semi-solid depot forms
Data Source
AI summary
Compositions and methods for suppressing ovarian function in subjects with hormone receptor-positive breast cancer.