Oxidized Avidin Inhalation Formulation for Lung Targeting

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Solution Overview

Problem

Current methods for delivering therapeutic agents to the lungs via inhalation face challenges such as short lung residence time, high clearance rates, and systemic side effects, making it difficult to effectively treat inoperable and diffuse lung diseases like lung cancer and cystic fibrosis.

Innovation Solution

A pharmaceutical formulation of oxidized avidin or biotinylated therapeutic agents is used for targeted delivery through inhalation, where oxidized avidin links to lung epithelial cells, allowing for stable localization of biotinylated therapeutics, reducing systemic exposure and minimizing side effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If conventional inhalation therapy is used to deliver therapeutic agents to the lungs, then the treatment can be administered non-invasively, but the drug residence time in the lungs is short and clearance rate is high, limiting therapeutic efficacy

Engineering Contradiction:
Improvedrug residence time in lungsVSAvoidclearance rate
Core Design Contradiction:
Duration of action of moving objectVSProductivity

Solution Approach 1:

The patent uses oxidized avidin as an intermediary substance that binds to lung tissue and captures biotinylated therapeutic agents, creating a temporary reservoir that releases drugs slowly. This intermediary system transforms the rapid clearance scenario into a sustained release scenario, extending drug residence time from minutes to hours while maintaining low clearance rates.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies preliminary action by first administering oxidized avidin to the lungs before delivering the biotinylated therapeutic agent. The oxidized avidin pre-conditions the lung tissue by creating binding sites that will capture and retain the subsequent therapeutic agent, ensuring extended residence time before the actual therapy is delivered.

Inventive Principle:
Principle #10Preliminary action

2Adaptability or versatility

If systemic therapy is used to treat diffuse lung diseases, then the therapeutic agent can reach all lung regions, but significant side effects occur due to systemic exposure

Engineering Contradiction:
Improvecoverage of lung regionsVSAvoidsystemic side effects
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by creating a lung-specific targeting system where oxidized avidin binds preferentially to lung tissue through interaction with lung epithelial cells. This localizes the therapeutic effect to the lungs while minimizing systemic exposure, as the biotinylated therapeutic agents are captured and retained at the target site rather than distributing throughout the body.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent utilizes the natural affinity between avidin and biotin, along with the endogenous lung clearance mechanisms, to create a self-contained therapeutic system. The oxidized avidin-biotin complex leverages the lung's own cellular structures and clearance pathways to maintain localized therapy, reducing the need for external intervention and minimizing systemic side effects.

Inventive Principle:
Principle #25Self-service

3Reliability

If frequent inhalation therapy is administered to maintain therapeutic effect, then treatment efficacy can be maintained, but patient compliance deteriorates and life quality decreases

Engineering Contradiction:
Improvetreatment efficacyVSAvoidpatient compliance
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent achieves continuity of useful action by creating a sustained release system where the oxidized avidin-biotin complex continuously releases therapeutic agents over an extended period. This transforms discrete, frequent administrations into a continuous therapeutic effect that persists for hours after a single inhalation, maintaining reliable treatment efficacy while dramatically reducing administration frequency and improving patient compliance.

Inventive Principle:
Principle #20Continuity of useful action

4Speed

If aerosolized therapeutic agents are inhaled to reach deep lung regions, then direct lung delivery is achieved, but diffusion to blood and systemic absorption remains problematic

Engineering Contradiction:
Improvedelivery speed to lungVSAvoidsystemic absorption
Core Design Contradiction:
SpeedVSQuantity of substance

Solution Approach 1:

The patent uses oxidized avidin as an intermediary that intercepts biotinylated therapeutic agents in the lung tissue and prevents their diffusion into the bloodstream. The avidin-biotin complex acts as a molecular trap that retains the therapeutic agent at the target site, achieving fast delivery to the lung while blocking unwanted systemic absorption through the pulmonary circulation.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

This approach enables efficient and stable delivery of therapeutic agents directly to the lungs, reducing the need for frequent administration and minimizing systemic side effects, while maintaining the chemical integrity of the protein, thus improving the therapeutic index and treatment efficacy for lung diseases.

Implementation Method 1

pharmaceutical formulation of oxidized avidin or biotinylated therapeutic agents is used for targeted delivery through inhalation

Methodology Applied
Scientific EffectAerosol: Aerosol

Implementation Method 2

oxidized avidin links to lung epithelial cells

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 3

a sterile buffer solution at acidic pH, wherein said buffer is preferably sodium acetate

Methodology Applied
Scientific EffectBuffer solution:

Implementation Method 4

a non-ionic agent selected from the group comprising mannitol, glycerol, glucose, lactose, trehalose, sucrose, propylene-glycol, sorbitol, xylitol, polyethylene-glycol, ethanol and isopropanol

Methodology Applied
Scientific EffectSurfactant: Surfactant

Data Source

PatentEP2739314B1Pharmaceutical composition of oxidised avidin suitable for inhalation
Publication Date: 2019.05.22 ALFASIGMA SPA
  • EP2739314B1 patent drawingFigure 1
  • EP2739314B1 patent drawingFigure 2
  • EP2739314B1 patent drawingFigure 3

AI summary

The present invention describes oxidized avidin, suitable for inhalation, for conditioning the lung affected by inoperable/diffuse diseases, enabling the targeted delivery of biotinylated therapeutic agents to it.