Radioprotectant Formulations for Protein Stability in E-Beam Sterilization

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Solution Overview

Problem

Radiation sterilization methods, such as electron beam and gamma ray exposure, can damage medical devices like glucose sensors by altering polymer structures and reducing their functionality, limiting the range of materials and designs available for medical devices.

Innovation Solution

The use of aqueous radioprotectant formulations containing reactive oxygen species like nitrates, sulphates, and phosphates, along with antioxidants and saccharides, to protect sensor components from radiation damage during sterilization by absorbing free electron energy and mitigating oxidative stress.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If radiation sterilization is used to sterilize medical devices, then sterilization effectiveness is improved, but damage to polymer structures and functional macromolecules occurs

Engineering Contradiction:
Improvesterilization effectivenessVSAvoidpolymer structure integrity
Core Design Contradiction:
ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent introduces radioprotectant formulations containing antioxidants and free radical scavengers as intermediary substances that mediate between the radiation sterilization process and the polymer/ macromolecule structures. These formulations absorb the harmful effects of radiation before they can damage the functional components, allowing sterilization to proceed while protecting the structural integrity of polymers and proteins.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the harmful free radicals and ionization effects of radiation into beneficial protective mechanisms by using radioprotectant formulations. The antioxidants and scavengers in these formulations are designed to interact with radiation-induced species, transforming the harmful radiation effects into a controlled process that actually protects the functional macromolecules while still achieving sterilization.

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

2Productivity

If high-energy radiation is used to kill microorganisms, then sterilization capability is improved, but free radical formation and macromolecule damage increase

Engineering Contradiction:
Improvesterilization capabilityVSAvoidfree radical formation
Core Design Contradiction:
ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful free radicals generated by high-energy radiation into beneficial protective mechanisms. The radioprotectant formulations contain antioxidants and free radical scavengers that interact with these radiation-induced species, transforming them from damaging agents into controlled intermediates that ultimately protect the functional macromolecules while maintaining sterilization effectiveness.

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

Solution Approach 2:

The patent introduces radioprotectant formulations as intermediary substances that mediate between the high-energy radiation process and the functional macromolecules. These formulations contain antioxidants and scavengers that serve as intermediaries, absorbing the harmful free radical effects before they can damage proteins and polymers, thereby enabling high-productivity sterilization without macromolecule degradation.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If radiation sterilization is applied to medical devices with protein components, then sterilization is achieved, but protein structure and sensor functionality are compromised

Engineering Contradiction:
Improvesterilization achievementVSAvoidsensor functionality
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent introduces radioprotectant formulations containing antioxidants and free radical scavengers as intermediary substances that protect protein components during radiation sterilization. These formulations are applied to the sensor device before sterilization, creating a protective layer that mediates between the radiation process and the sensitive protein structures, thereby maintaining sensor functionality while achieving sterilization.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs parameter changes by modifying the chemical environment of the sensor device through radioprotectant formulations. By changing the concentration and type of antioxidants and scavengers in the formulation, the patent optimizes the protection parameters to maintain protein structure stability and sensor functionality throughout the radiation sterilization process.

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 described formulations help maintain the glucose sensitivity of sensors after radiation sterilization, with significant retention of dose response and sensor performance, even at high radiation doses, compared to control formulations without these excipients.

Implementation Method 1

reactive oxygen species (ROS), such as nitrates, sulphates, and phosphates and other electron accepting compounds... act as radical oxidative scavengers that can protect proteins (e.g. glucose oxidase) and other radiation sensitive sensor components... by absorbing the free electron energy

Methodology Applied
Scientific EffectFree electron absorption: Absorption (EM radiation)

Implementation Method 2

High-energy radiation tends to produce ionization and excitation in polymer molecules, as well as free radicals

Methodology Applied
Scientific EffectIonization: Ionisation

Implementation Method 3

High-energy radiation tends to produce ionization and excitation in polymer molecules, as well as free radicals

Methodology Applied
Scientific EffectExcitation:

Implementation Method 4

These energy-rich species can react with macromolecules present in medical products and undergo dissociation, abstraction, chain scission and cross-linking

Methodology Applied
Scientific EffectFree radical reaction: Oxidation

Data Source

PatentEP3303604B1Protective agents against e-beam irradiation for proteins in optical sensing chemistry
Publication Date: 2019.08.07 MEDTRONIC MINIMED INC
  • EP3303604B1 patent drawingFigure 1A~1C
  • EP3303604B1 patent drawingFigure 1D
  • EP3303604B1 patent drawingFigure 2

AI summary

Medical devices are typically sterilized in processes used to manufacture such products and their sterilization by exposure to radiation is a common practice. Radiation has a number of advantages over other sterilization processes including a high penetrating ability, relatively low chemical reactivity, and instantaneous effects without the need to control temperature, pressure, vacuum, or humidity. Unfortunately, radiation sterilization can compromise the function of certain components of medical devices. For example, radiation sterilization can lead to loss of protein activity and/or lead to bleaching of various dye compounds. Embodiments of the invention provide methods and materials that can be used to protect medical devices from unwanted effects of radiation sterilization.