Nitro-Fatty Acid Microbubbles for Targeted Inflammation Therapy

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Solution Overview

Problem

Microvascular obstruction (MVO) following percutaneous coronary intervention for acute myocardial infarctions is prevalent, leading to worse clinical outcomes due to mechanisms like downstream micro-embolization, mechanical obstruction, myocardial edema, inflammation, and oxidative stress, with current treatments lacking targeted and localized delivery of nitro-fatty acids (NFAs) to affected areas.

Innovation Solution

A microbubble composition comprising a lipid-based shell with a nitro-fatty acid or its amphiphilic ester, combined with ultrasound for targeted delivery to specific tissue sites, allowing for localized release of NFAs to reduce inflammation and thrombolysis in microvascular obstructions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If NFAs are administered systemically, then therapeutic coverage is comprehensive, but targeted delivery to specific pathology sites is lost

Engineering Contradiction:

Improvetherapeutic coverageVSAvoidtargeted delivery accuracy

Core Design Contradiction:

Quantity of substanceVSMeasurement precision

Solution Approach 1:

The patent segments the therapeutic delivery system by encapsulating NFAs within individual microbubbles that can be selectively targeted to specific pathology sites. Each microbubble acts as an independent delivery vehicle, allowing comprehensive coverage through multiple targeted microbubbles rather than relying on a single systemic administration approach.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces microbubbles as intermediary carriers that mediate between the NFA therapeutic agent and the target pathology. These microbubble intermediaries enable precise localization to inflammatory sites while protecting and delivering the NFA payload, thereby achieving both targeted delivery and therapeutic efficacy.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If high doses of NFAs are administered, then therapeutic effectiveness is enhanced, but risk of adverse effects from overdosing increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidadverse effects from overdosing

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by concentrating high doses of NFAs specifically at the pathology site through targeted microbubble accumulation, while maintaining low systemic concentrations. This spatial differentiation allows high local therapeutic effectiveness without exposing the entire organism to high doses that would cause adverse effects.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent implements partial action by delivering excessive amounts of NFAs locally to the inflammatory site through accumulated microbubbles, while the rest of the body receives minimal exposure. This localized excessive action achieves therapeutic effectiveness at the target site without causing systemic overdosing adverse effects.

Inventive Principle:

Principle #16Partial or excessive action

3Area of stationary object

If NFAs are delivered systemically, then distribution is widespread, but concentration at specific tissue sites is insufficient

Engineering Contradiction:

Improvedistribution areaVSAvoidlocal concentration

Core Design Contradiction:

Area of stationary objectVSQuantity of substance

Solution Approach 1:

The patent segments the therapeutic delivery into multiple discrete microbubble units that can independently navigate and accumulate at target sites. This segmentation allows widespread distribution through numerous microbubbles while each microbubble contributes to high local concentration at its specific target location.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent changes the physical state and delivery parameters by using microbubble encapsulation, which alters the pharmacokinetics and tissue distribution characteristics of NFAs. This enables the substance to achieve both widespread distribution through blood flow and high local concentration through microbubble accumulation and subsequent release at target sites.

Inventive Principle:

Principle #35Parameter changes

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 microbubble composition effectively delivers NFAs to sites of inflammation and obstruction, enhancing therapeutic efficacy by reducing inflammation and thrombosis, improving microvascular perfusion, and preventing further fibrosis, thereby improving clinical outcomes.

Implementation Method 1

administering an ultrasound pulse to the site effective to deliver the nitro-fatty acid to the site or to disrupt the microbubble

Methodology Applied

Scientific EffectUltrasound: Ultrasound

Implementation Method 2

administering an ultrasound pulse to the site effective to deliver the nitro-fatty acid to the site or to disrupt the microbubble

Methodology Applied

Scientific EffectAcoustic cavitation: Acoustic Cavitation

Data Source

PatentUS20230065014A1Nitro-Fatty Acid-Containing Microbubbles and Uses Therefor

Publication Date: 2023.03.02 UNIV OF PITTSBURGH OF THE COMMONWEALTH SYST OF HIGHER EDUCATION

AI summary

Provided herein are microbubble compositions comprising nitro-fatty acids and/or esters thereof, such as amphiphilic esters or allyl esters thereof. Also provided are methods of reducing local inflammation at a site in a patient comprising delivering the microbubbles to a site of inflammation in the patient and applying ultrasound to the microbubbles. The methods may be used to treat fibrosis or cancer.