Hypotonic Rectal Formulation for HIV Prophylaxis

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Solution Overview

Problem

There is a need for improved formulations and methods to prevent and treat sexually transmitted infections (STIs), particularly for men who have sex with men (MSM), that can be effectively administered before intercourse, addressing the risk of HIV and STIs associated with douching/enema practices.

Innovation Solution

Development of hypotonic enema formulations containing a combination of Tenofovir (TFV) and Q-Griffithsin (Q-GRFT) as a Pre-Exposure Prophylaxis (PrEP) option, which are stable and easy to manufacture, and can be delivered rectally to provide dual protection against HIV/STIs, utilizing a therapeutic composition with excipients like disaccharides or sugar polyols and a buffer to maintain pH and osmolality within specific ranges.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If douching/enema procedures are used for rectal delivery, then drug administration is achieved, but risk of HIV/STI transmission increases

Engineering Contradiction:

Improvedrug administrationVSAvoidHIV/STI transmission risk

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent formulates the enema solution with specific osmolality parameters (hypotonic range) and pH levels to create a formulation that is both comfortable for rectal administration and effective at preventing HIV/STI transmission. The controlled parameters ensure the solution maintains epithelial integrity while delivering antiretroviral drugs.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention combines multiple active ingredients (tenofovir and griffithsin) with specific excipients and buffers to create a composite enema formulation. This composite structure provides dual protection mechanisms while maintaining solution stability and effectiveness for rectal delivery.

Inventive Principle:

Principle #40Composite materials

2Productivity

If hypotonic enema formulation is used, then drug penetration and bioavailability are enhanced, but formulation stability over time becomes challenging

Engineering Contradiction:

Improvedrug penetration and bioavailabilityVSAvoidformulation stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent carefully controls the osmolality and pH parameters of the hypotonic formulation to achieve optimal drug penetration while maintaining stability. The specific parameter ranges are designed to prevent precipitation, degradation, or unwanted interactions of the active ingredients during storage.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The formulation includes buffers and excipients that act as intermediaries to maintain the stability of active ingredients in the hypotonic environment. These components prevent degradation and maintain the desired osmolality and pH levels throughout the product shelf life.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If combination of Tenofovir and Q-Griffithsin is used, then dual protection against HIV/STI is achieved, but manufacturing complexity increases

Engineering Contradiction:

Improvedual protection effectivenessVSAvoidmanufacturing complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines tenofovir and griffithsin into a single integrated enema formulation, allowing both drugs to be administered simultaneously through one procedure. This merging approach maintains dual protection effectiveness while simplifying the overall administration process compared to separate treatments.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The formulation is designed to achieve homogeneous distribution of both active ingredients throughout the solution, ensuring consistent dosing and effectiveness. This homogeneity simplifies manufacturing quality control and ensures reliable dual protection.

Inventive Principle:

Principle #33Homogeneity

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 formulations offer stable, effective, and reproducible dual protection against HIV/STIs, maintaining stability and bioactivity over time, ensuring safe and efficient delivery of TFV and Q-GRFT, enhancing drug penetration and bioavailability, and maintaining the integrity of the rectal epithelium.

Implementation Method 1

The formulations are hypotonic with an osmolality from about 123 mOsm/kg to about 167 mOsm/kg

Methodology Applied

Scientific EffectOsmosis: Osmosis

Implementation Method 2

adjusting the pH to between 6.5-8... maintaining pH and osmolality within specific ranges

Methodology Applied

Scientific EffectBuffering:

Implementation Method 3

dissolving the Q-GRFT lyophilized with a disaccharide or sugar polyol... in an aqueous solvent, followed by drying, lyophilizing, or spray-drying

Methodology Applied

Scientific EffectLyophilization: Freeze Drying

Data Source

PatentUS20240374681A1Formulation for Co-Administration of Q-GRFT and Tenofovir

Publication Date: 2024.11.14 UNIV OF PITTSBURGH OF THE COMMONWEALTH SYST OF HIGHER EDUCATION

AI summary

Provided herein are stable hypotonic or isotonic formulations containing active ingredients, such as antiviral compositions, or anti-retroviral compositions for intrarectal delivery to provide prophylaxis against viral infections.