Thrombin Microcapsules Supercritical CO2 Drying

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Solution Overview

Problem

Current spray drying processes for producing thrombin powder are limited by enzyme sensitivity to high temperatures and shear stress, leading to denaturation and reduced potency, resulting in low thrombin concentrations and inefficient production.

Innovation Solution

Control of spray drying parameters such as drying gas flow rate and temperature, along with the use of specific aqueous compositions with low concentrations of stabilizing protein carriers and carbohydrates, to produce thrombin powders with high activity and concentration, achieving up to 24 IU/mg with less than 5% water content and high density.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If spray drying is used to produce thrombin powder, then productivity and mass yield are improved, but thrombin activity is reduced due to denaturation from high temperature and shear stress

Engineering Contradiction:

Improvemass yieldVSAvoidthrombin activity

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent changes the physical-chemical parameters of the drying process by using supercritical carbon dioxide (pressure above 73 atm, temperature above 31°C) instead of conventional hot air drying. This supercritical fluid extraction method achieves complete drying without thermal denaturation, producing thrombin powder with 100% retained activity while maintaining high productivity and mass yield.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses carbon dioxide in its supercritical state as an inert drying medium that eliminates harmful thermal effects. The supercritical CO2 environment provides a non-denaturing atmosphere that preserves thrombin structure and function while efficiently removing water to produce dry, stable powder with high mass yield.

Inventive Principle:

Principle #39Inert atmosphere (Inert environment)

2Quantity of substance

If high temperature drying is used to remove water, then water content is reduced, but thrombin denaturation increases

Engineering Contradiction:

Improvewater contentVSAvoidthermal denaturation

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent exploits the phase transition of carbon dioxide between supercritical and gaseous states. By controlling pressure and temperature, CO2 transitions to a supercritical state for extraction, then returns to gaseous state for easy removal, achieving complete drying without thermal damage to thrombin.

Inventive Principle:

Principle #36Phase transitions

Solution Approach 2:

The patent replaces the thermal mechanism (heat-driven evaporation) with a mechanical-solvent mechanism (supercritical fluid extraction). Instead of using heat to remove water, the system uses supercritical CO2 as a solvent that physically extracts water and then evaporates without requiring high temperatures, eliminating thermal denaturation.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 method results in highly concentrated, stable thrombin powders with high activity and density, improving mass yield and reducing adhesion issues during processing, while maintaining thrombin's biological activity and allowing for efficient storage and reconstitution.

Implementation Method 1

spray drying involves atomization of a liquid, such as a solution, suspension or emulsion, for example by spraying through a spray nozzle while contacting with an atomizing gas to form spray particles; by two-fluid nozzle atomization, wherein spray is created by combination of a liquid flow and a gas flow, in which the atomization energy is provided by the gas flow

Methodology Applied

Scientific EffectEvaporation: Evaporation

Implementation Method 2

Methodology Applied

Scientific EffectAtomization:

Implementation Method 3

Formation of spray particles is followed by drying of the spray in a flow of a hot gas (e.g. air or nitrogen) provided by a drying gas conduit. The spray particles dry rapidly into powder

Methodology Applied

Scientific EffectEvaporation: Evaporation