Sulfur Colloid Viscosity Control via Thermal Parameter Changes

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Solution Overview

Problem

The use of gelatin in sulfur colloid radiopharmaceutical compositions increases viscosity, leading to gelling issues during manufacturing, making it difficult to filter and fill pre-lyophilized compositions, and affects the stability and shelf life of the final product.

Innovation Solution

A pharmaceutical composition of sulfur colloid is prepared by mixing gelatin with water, heating the colloidal support agent to at least 100°C for 110-150 minutes, adding a reducing agent and a chelating agent, which maintains viscosity between 1-100 cP for extended periods, preventing gelling and ensuring stability and radiochemical purity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If gelatin is used as colloid support agent, then stability and protection of sulfur colloid is improved, but viscosity increases and gelling occurs during manufacturing

Engineering Contradiction:
ImprovestabilityVSAvoidviscosity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies parameter changes by carefully controlling the heating temperature (maintaining between 100-121°C) and heating time (110-150 minutes) to prevent gelatin from transitioning to a gelled state while maintaining colloidal stability. This thermal parameter control resolves the contradiction between stability and manufacturability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements preliminary action by pre-heating the gelatin-containing bulk solution to the specified temperature range before adding sulfur colloid and other components. This preliminary thermal treatment ensures the gelatin remains in a soluble, non-gelled state throughout the manufacturing process, preventing viscosity issues while maintaining stability.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If pre-lyophilized composition is exposed to lower temperature conditions, then stability is maintained, but viscosity increases and solidifies to thick gel

Engineering Contradiction:
ImprovestabilityVSAvoidviscosity
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent uses parameter changes by establishing a minimum temperature threshold (100-121°C) that prevents the gelatin-sulfur colloid system from gelling. By maintaining temperatures above this threshold during manufacturing and storage, the composition remains fluid and operable while保持稳定性.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies beforehand cushioning by incorporating sufficient heating time (110-150 minutes) into the manufacturing process to ensure complete dissolution and stabilization of gelatin before the composition is cooled or stored. This preliminary thermal processing cushions against subsequent gelling that would occur at lower temperatures.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Ease of manufacture

If heating time and temperature are extended, then viscosity control and gelling prevention is improved, but energy consumption and process complexity increases

Engineering Contradiction:
Improveviscosity controlVSAvoidheating energy
Core Design Contradiction:
Ease of manufactureVSUse of energy by stationary object

Solution Approach 1:

The patent optimizes the heating parameters to a specific range (100-121°C for 110-150 minutes) that achieves effective viscosity control and gelling prevention without excessive energy consumption. This optimized parameter range balances manufacturing ease with energy efficiency.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent implements continuous heating throughout the 110-150 minute period to ensure consistent temperature maintenance and prevent gelling. This continuous thermal action ensures uniform viscosity control throughout the bulk solution without requiring intermittent high-energy heating cycles.

Inventive Principle:
Principle #20Continuity of useful action

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 solution provides stable, high radiochemical purity sulfur colloid compositions with extended shelf life and improved bio-distribution, suitable for industrial production and diagnostic use, by controlling viscosity and preventing gelling during manufacturing.

Implementation Method 1

heating the colloidal supporting agent for at least 100° C. for about 110-150 minutes

Methodology Applied
Scientific EffectHeating: Heating

Implementation Method 2

adding reducing agent

Methodology Applied
Scientific EffectReduction: Reduction

Data Source

PatentUS11471543B2Pharmaceutical compositions of sulfur colloid and processes thereof
Publication Date: 2022.10.18 JUBILANT DRAXIMAGE INC

AI summary

The present invention relates to stable pharmaceutical compositions of sulfur colloid, which advantageously provide a high radiochemical purity to 99mTc-pertechnetate without causing the gel formation. The compositions include pre-lyophilized and lyophilized compositions of sulfur colloid. It also relates to a non-radioactive kit which upon reconstitution with 99mTc-pertechnetate solution gives stabilized 99mmTc-Sulfur colloid radiopharmaceutical composition. Further, the process for preparation of said compositions and their use for diagnostic purposes are also disclosed.