Androgen–Aromatase Inhibitor Pellets With Multi-Phasic Release
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Solution Overview
Problem
Existing treatments for conditions like high mammographic breast density, breast pain, and autoimmune inflammatory mastitis fail to effectively increase intra-tissue dihydrotestosterone (DHT) levels while reducing oestradiol levels without causing significant perturbations in serum oestradiol levels, leading to undesirable side effects.
Innovation Solution
A pharmaceutical formulation comprising an androgenic agent and an aromatase inhibitor, delivered via a subcutaneous pellet, provides a multi-phasic release pattern to achieve a high intra-tissue DHT to oestradiol ratio by initially blocking oestradiol production and then allowing gradual conversion to DHT, avoiding systemic aromatase inhibitor overexposure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If testosterone is delivered to tissue in women, then DHT levels increase, but androgenic side-effects occur due to high aromatase enzyme activity converting testosterone to oestradiol
Solution Approach 1:
The patent segments the release of testosterone and aromatase inhibitor into distinct temporal phases. The formulation first releases testosterone to establish baseline androgen levels, then releases aromatase inhibitor to block conversion to oestradiol, creating a segmented temporal profile that prevents simultaneous high androgen and high oestradiol exposure
Solution Approach 2:
The patent applies preliminary action by delivering testosterone first before delivering the aromatase inhibitor. This sequence ensures that testosterone is already present in the tissue when the aromatase inhibitor is released, allowing the inhibitor to selectively block the conversion of the pre-existing testosterone to oestradiol without preventing androgenic effects
2Quantity of substance
If aromatase inhibitor is used to reduce oestradiol levels, then breast density decreases, but serum oestradiol levels are significantly perturbed causing side effects
Solution Approach 1:
The patent achieves local quality by delivering the aromatase inhibitor in a formulation that provides high local concentration at the injection site where it blocks aromatase activity, while the overall systemic exposure is controlled through the multi-phasic release profile that prevents sustained high serum levels
Solution Approach 2:
The patent employs periodic action through its multi-phasic release profile, where the aromatase inhibitor is released in controlled pulses rather than continuously. The formulation provides initial high concentration to block aromatase activity, then allows gradual reduction, creating a periodic release pattern that maintains local effectiveness while minimizing systemic perturbation
3Duration of action of stationary object
If continuous zero-order kinetic dosing is used, then sustained hormone levels are maintained, but intra-tissue DHT to oestradiol ratio cannot be optimized
Solution Approach 1:
The patent transitions from static zero-order kinetic dosing to dynamic multi-phasic release. The formulation dynamically adjusts the release rate of testosterone and aromatase inhibitor over time, providing high initial concentration to establish favorable DHT to oestradiol ratio, then gradually reducing concentration to maintain sustained effect without optimizing the ratio throughout the entire duration
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
This approach reduces mammographic breast density, breast stiffness, and autoimmune inflammatory mastitis by maintaining a balanced hormone ratio locally, minimizing systemic side effects and improving breast tissue stability and androgen receptor expression.
Implementation Method 1
the formulation upon administration to a subject provides a sustained release multi-phasic concentration pattern in the blood of the subject over time
Data Source
AI summary
The present disclosure is directed formulations, delivery systems and/or methods of use that have a novel a sustained release multi-phasic concentration pattern that may be used, among other things, for reducing mammographic breast density and/or breast stiffness in warm-blooded animals. For example, the formulation may comprise: the administration of an effective amount of androgenic agent and an effective amount of an aromatase inhibitor to a subject that provides a sustained release multi-phasic concentration pattern in the blood of the subject over time as measured by serum concentration for the androgen and plasma concentration for the aromatase inhibitor and improves, amoung other things, breast tissue stabilization and/or increases of the levels of androgen receptor expression. The present disclosure is also directed to the use of an effective amount of an androgenic agent in combination with an effective amount of an aromatase inhibitor for the prophylaxis or treatment of autoimmune inflammatory mastitis (AIM) in a patient in need thereof. Autoimmune inflammatory mastitis includes the conditions of idiopathic inflammatory macromastia, plasma cell mastitis, granulomatous mastitis.