Pharmaceutical formulations and systems for delivery of an androgenic agent and an aromatase inhibitor with sustained multi-phasic release profiles and methods of use
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11524014-B2
Publication Date
2022-12-13
Expiration Date
Abstract
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, among 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 15 need thereof. Autoimmune inflammatory mastitis includes the conditions of idiopathic inflammatory macromastia, plasma cell mastitis, granulomatous mastitis.
Core Innovation
The invention relates to pharmaceutical formulations and delivery systems combining an androgenic agent and an aromatase inhibitor, where the pharmaceutical formulation provides a sustained release multi-phasic concentration pattern in the blood over time as measured by serum concentration for the androgen and plasma concentration for the aromatase inhibitor. The sustained release multi-phasic concentration pattern is defined by time periods in which an early androgen concentration profile is characterized by an androgen Tmax and a rising aromatase-inhibitor level, followed by later aromatase-inhibitor Tmax and subsequent phases where the aromatase inhibitor declines while the androgen reaches a second peak then decreases in parallel.
In the described embodiments, the delivery system includes binding-agent-compressed subcutaneous pellets that provide multi-phasic pharmacokinetics. The approach is configured to increase a tissue DHT/estradiol ratio while minimizing systemic estradiol deprivation, and it is described with supporting pharmacokinetic and pharmacodynamic outcomes based on serum androgen levels and plasma aromatase-inhibitor levels over time.
The invention is directed to treating autoimmune inflammatory mastitis using the combination of an androgenic agent with an aromatase inhibitor in a patient in need thereof, including enumerated autoimmune inflammatory mastitis subtypes such as idiopathic inflammatory macromastia, plasma cell mastitis, and granulomatous mastitis. The document also describes downstream effects including induction of breast CD36 and stabilization or increased androgen receptor expression, with reported associated improvements in breast pain and inflammation and imaging- or risk-related outcomes such as mammographic breast density reduction.
Claims Coverage
The independent claim covers a treatment method for autoimmune inflammatory mastitis using an androgenic agent combined with an aromatase inhibitor, where a sustained release multi-phasic concentration pattern is produced and measured over time by serum androgen and plasma aromatase-inhibitor concentrations. The cited independent claim is the only independent claim explicitly provided in the partial content, with dependent claims refining drug selection and formulation/administration constraints.
Treatment of autoimmune inflammatory mastitis by combined androgenic agent and aromatase inhibitor
A method for the treatment of autoimmune inflammatory mastitis in a patient in need thereof, comprising administering an effective amount of an androgenic agent in combination with an effective amount of an aromatase inhibitor.
Sustained release multi-phasic concentration pattern for androgen and aromatase inhibitor
The pharmaceutical formulation provides a sustained release multi-phasic concentration pattern in the blood of the patient over time as measured by serum concentration for the androgen and plasma concentration for the aromatase inhibitor.
The claim coverage is centered on combined androgenic-agent and aromatase-inhibitor administration for autoimmune inflammatory mastitis, with the key defining limitation being the sustained release multi-phasic blood concentration pattern tracked by serum androgen and plasma aromatase-inhibitor levels.
Stated Advantages
Increasing tissue DHT/estradiol ratio while minimizing systemic estradiol deprivation.
Reducing mammographic breast density (e.g., %VBD/AVBD) and related imaging/risk outcomes.
Reducing breast stiffness and breast pain.
Associated improvements in pain and inflammation in autoimmune inflammatory mastitis subtypes.
Induction of breast CD36 and stabilization or increase in androgen receptor expression.
Documented Applications
Treatment of autoimmune inflammatory mastitis in a patient in need thereof, including idiopathic inflammatory macromastia, plasma cell mastitis, and granulomatous mastitis.
Treatment/prophylaxis of autoimmune inflammatory mastitis subtypes as described in the document.
Reduction of mammographic breast density and associated imaging/risk outcomes as reported in the document.
Interested in licensing this patent?