Transdermal Progesterone Solubilization via Co-Solvents

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Solution Overview

Problem

Current transdermal hormone replacement therapies face challenges in solubilizing natural progesterone due to its insolubility, leading to higher dosage requirements and limited commercialization of patches using natural progesterone, while prevailing technologies rely on synthetic progestins, which may have different side effects and patient compliance issues with separate estrogen and progesterone dosing regimens.

Innovation Solution

Development of transdermal pharmaceutical formulations that solubilize progesterone and optionally combine it with estrogen, allowing for cyclic/sequential and continuous-combined dosing regimes via transdermal patches, packaged in a single package to improve patient compliance and reduce side effects by mimicking natural hormone delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If natural progesterone is used in transdermal formulations, then patient compliance and side effect profile improve, but solubility and formulation stability worsen

Engineering Contradiction:
Improvepatient complianceVSAvoidsolubility
Core Design Contradiction:
Ease of operationVSQuantity of substance

Solution Approach 1:

The patent uses solubilizing agents and co-solvents as intermediary substances to bridge the incompatibility between natural progesterone and the transdermal patch matrix. These intermediaries enable the insoluble progesterone to be incorporated into the patch formulation while maintaining its therapeutic efficacy and improving patient compliance through natural hormone replacement.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the physical and chemical parameters of the progesterone formulation by changing its solubility characteristics through the use of specific solvents, co-solvents, and solubilizing agents. This allows the natural progesterone to be delivered at physiologically relevant doses through transdermal absorption without compromising formulation stability.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If synthetic progestins are used instead of natural progesterone, then formulation solubility improves, but side effects and patient compliance worsen

Engineering Contradiction:
ImprovesolubilityVSAvoidside effects
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent converts the apparent disadvantage of natural progesterone's poor solubility into a benefit by developing sophisticated solubilization techniques. This approach allows the use of natural progesterone with its favorable side effect profile and patient acceptance, while overcoming the solubility challenge through innovative formulation science rather than resorting to synthetic alternatives.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

3Adaptability or versatility

If separate estrogen and progesterone dosing regimens are used, then dosing flexibility improves, but patient compliance and treatment complexity worsen

Engineering Contradiction:
Improvedosing flexibilityVSAvoidpatient compliance
Core Design Contradiction:
Adaptability or versatilityVSEase of operation

Solution Approach 1:

The patent combines estrogen and progesterone into a single transdermal patch formulation, merging two separate dosing regimens into one unified delivery system. This integration maintains the ability to independently adjust hormone doses while dramatically simplifying patient compliance by eliminating the need for multiple separate applications or coordination of different dosing schedules.

Inventive Principle:
Principle #5Merging (Combining)

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 solubilized progesterone and estrogen formulations enhance patient compliance and reduce side effects by providing consistent hormone delivery, addressing the limitations of existing therapies with natural progesterone and synthetic progestins, and improving the treatment of menopause-related symptoms.

Implementation Method 1

transdermal delivery systems...delivering a hormone, or a combination of hormones, through the skin

Methodology Applied
Scientific EffectDiffusion: Diffusion

Data Source

PatentEP2806742B1Transdermal hormone replacement therapies
Publication Date: 2019.03.27 THERAPEUTICSMD INC
  • EP2806742B1 patent drawingFigure 1
  • EP2806742B1 patent drawingFigure 2~3
  • EP2806742B1 patent drawingFigure 4

AI summary

Hormone replacement therapies are provided comprising solubilized progesterone alone and optionally with an estrogen, cyclic/sequential and continuous-combined dosing, and administered via transdermal HRT delivery systems.