Progesterone Intravaginal Ring Polymorph I
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current progesterone formulations for treating infertility and pregnancy complications often result in high systemic levels leading to side effects and vaginal bleeding, requiring frequent administration and high doses, which can be inconvenient and uncomfortable for patients.
Innovation Solution
Development of an intravaginal device comprising progesterone in polymorphic form I, with at least 75% of the progesterone in this form, which provides low serum levels and minimizes vaginal bleeding, allowing for prolonged use without replacement or additional formulations, using a process involving mixing with a pharmaceutically acceptable polymeric composition and curing at temperatures below 120°C.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high doses of oral progesterone are administered to achieve sufficient intrauterine levels, then endometrial transformation is achieved, but hepatic first-pass effect reduces bioavailability and builds up progesterone metabolites in blood causing unwanted side effects
Solution Approach 1:
The patent uses a vaginal delivery system as an intermediary route to bypass hepatic first-pass metabolism. The progesterone is delivered directly to the uterus through the vaginal mucosa, avoiding the liver's metabolic processing that occurs with oral administration. This intermediary delivery path eliminates the build-up of harmful metabolites while maintaining effective intrauterine progesterone levels for endometrial transformation.
Solution Approach 2:
The patent replaces the oral administration mechanical system (swallowing pills that undergo hepatic processing) with a vaginal delivery system. This substitution changes the absorption pathway from gastrointestinal-hepatic to direct mucosal absorption, thereby eliminating the metabolic bottleneck that causes side effects while maintaining therapeutic efficacy.
2Quantity of substance
If intra-muscular progesterone is administered to achieve high serum levels, then sufficient progesterone is delivered, but uterine first-pass effect reduces efficacy and daily injections are painful and inconvenient
Solution Approach 1:
The patent extracts the progesterone delivery from the painful intra-muscular injection route and relocates it to the vaginal mucosa. This extraction eliminates the need for daily injections while maintaining sufficient progesterone levels. The vaginal delivery system allows for less frequent administration (e.g., weekly ring replacement) while achieving the same therapeutic effect without pain or inconvenience.
Solution Approach 2:
The patent changes the administration parameters from frequent daily injections to less frequent vaginal deliveries. By altering the delivery frequency and route parameters, the system achieves sustained progesterone levels without requiring daily patient intervention, thereby improving ease of operation and patient comfort.
3Ease of operation
If vaginal progesterone gel is used for easier administration, then pain is reduced, but daily dosing is required and leakage may occur reducing dose delivery
Solution Approach 1:
The patent incorporates progesterone into a vaginal ring during manufacturing, pre-loading the device with sufficient drug supply. This preliminary action ensures that the ring can deliver consistent doses over an extended period (e.g., one week) without requiring daily patient intervention or risking leakage, thereby improving both ease of operation and reliability of dose delivery.
Solution Approach 2:
The vaginal ring provides continuous progesterone release over an extended period through controlled diffusion through the vaginal mucosa. This continuous action eliminates the intermittent dosing required by gels and ensures consistent therapeutic levels without leakage, maintaining both ease of operation and reliability.
4Quantity of substance
If progesterone vaginal inserts or capsules are administered once or multiple times daily, then progesterone supplementation is achieved, but treatment discontinuation may occur due to cumulative burden
Solution Approach 1:
The patent merges multiple daily dosing events into a single weekly vaginal ring insertion. By combining the therapeutic function of multiple inserts or capsules into one sustained-release device, the system maintains adequate progesterone supplementation while dramatically reducing the cumulative treatment burden on patients, thereby minimizing treatment discontinuation.
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 device effectively transforms the endometrium into the secretory phase, maintains pregnancy, and reduces or avoids vaginal bleeding, offering improved patient comfort and safety with stable and controlled progesterone release over an extended period.
Implementation Method 1
Vaginal administration of progesterone generally results in higher endometrial progesterone levels when compared to the above administration routes
Data Source
AI summary
The invention relates to intravaginal devices, in particular rings, comprising progesterone in a particular polymorphic purity, methods for making such devices and therapeutic uses of said devices. In particular, the intravaginal devices comprise a high amount of progesterone polymorph I and are useful in the treatment of infertility in a female subject.