Nitroxide Radioprotector Formulations for Radiotherapy

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Solution Overview

Problem

Current topical formulations of nitroxide radioprotectors, such as Tempol, are unsuitable for administration shortly before radiotherapy as they leave residues that can cause severe burns when radiation is applied, necessitating the development of low-residue formulations that can be applied safely before radiotherapy.

Innovation Solution

Pharmaceutical compositions comprising a solvent and an effective amount of nitroxide radioprotectors like TEMPO or TEMPOL in a low-residue gel or thickened liquid form, which are designed to minimize residue and enhance absorption without causing a bolus effect during radiotherapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional topical formulations (creams, lotions, ointments) are used to deliver nitroxide radioprotectors, then the radioprotective effect is achieved, but residues are left on the skin that cause severe burns when radiation is applied

Engineering Contradiction:

Improveradioprotective effectVSAvoidtopical burning

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical state parameter of the formulation from semi-solid (cream, ointment) to liquid solution, and further optimizes by using volatile solvents that evaporate completely. This parameter change eliminates the residue that causes burning while maintaining the radioprotective efficacy of the nitroxide compound.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent extracts and eliminates the harmful residue component from the formulation by using volatile solvents that completely evaporate. The active radioprotective ingredient is separated from the vehicle, which disappears entirely, leaving no harmful residue on the skin before radiation delivery.

Inventive Principle:

Principle #2Taking out (Extraction)

2Duration of action of moving object

If topical formulations are applied shortly before radiotherapy, then the radioprotective effect is maximized, but traditional formulations leave residues that intensify radiation damage

Engineering Contradiction:

Improvetiming of administrationVSAvoidbolus effect

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent uses volatile solvents that serve as temporary delivery vehicles and then completely evaporate/disappear. This short-lived vehicle system allows the radioprotector to be present on the skin at the optimal time before radiation, then disappears without causing any delayed bolus effect or residue-related harm.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Ease of manufacture

If creams, lotions, or ointments are used as topical formulations, then the nitroxide radioprotector can be delivered to the skin, but the formulation leaves a residue that causes severe burns during radiotherapy

Engineering Contradiction:

Improveformulation typeVSAvoidsevere burns

Core Design Contradiction:

Ease of manufactureVSObject-affected harmful factors

Solution Approach 1:

The patent changes the formulation type parameter from semi-solid preparations (creams, lotions, ointments) to volatile liquid solutions. This parameter change fundamentally alters the behavior of the vehicle, allowing it to evaporate completely and leave no residue, thereby eliminating the severe burns caused by traditional formulations while maintaining ease of manufacture.

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

These compositions effectively ameliorate skin, mucous membrane, and hair follicle conditions associated with radiotherapy, reducing side effects like erythema, mucositis, and alopecia while preventing severe burns, thereby improving patient comfort and treatment outcomes.

Implementation Method 1

Some have previously suggested the use of Tempol, a stable nitroxide radical characterized by the chemical formula 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, as a topical formulation to ameliorate the effects of radiotherapy

Methodology Applied

Scientific EffectFree radical scavenging: Oxidation

Implementation Method 2

These references limit the topical use of Tempol to formulations selected from creams, lotions, shampoos, cream rinses, and ointments. It is now recognized that these kinds of topical formulations are unsuitable for administration shortly before the actual delivery of radiotherapy to the patient. Indeed, these product forms leave residues that can result in topical burning

Methodology Applied

Scientific EffectEvaporation: Evaporation

Data Source

PatentUS7625928B2Nitroxide radioprotector formulations and methods of use

Publication Date: 2009.12.01 MITOS INC

AI summary

Pharmaceutical compositions useful in preventing and treating negative side effects accompanying radiotherapy are disclosed. More particularly, new formulations that can be applied to the skin and mucous membranes of patients undergoing radiotherapy and methods of using these formulations are disclosed.