Cyclodextrin Polymer Conjugate Precipitation via Sub-Ambient Cooling

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

The scaling of cyclodextrin-containing polymer (CDP) therapeutic agent conjugate production for commercial use is challenging due to difficulties in precipitating CDP-therapeutic agent conjugates, which tend to adhere to mixing impellors and have reproducibility issues, necessitating improved methods for precipitation and particle generation.

Innovation Solution

A process involving the introduction of a polymer-containing solution into a cooled non-solvent, followed by agitation and controlled conditions to precipitate CDP-inhibitor conjugates, such as CDP-camptothecin conjugates, allowing for filtration and storage as solids or liquids, and subsequent formulation into pharmaceutical compositions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional precipitation method is used, then CDP-therapeutic agent conjugates can be precipitated, but the process is slow and requires multiple decantation and rinsing steps

Engineering Contradiction:

Improveprecipitation speedVSAvoidprocess complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent changes the temperature parameter of the non-solvent from conventional ambient temperature to sub-ambient temperatures (e.g., -70°C to -100°C), which dramatically accelerates the precipitation rate and enables single-step isolation without multiple decantation and rinsing operations

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent utilizes the phase transition properties of the non-solvent at sub-ambient temperatures to achieve rapid precipitation. By cooling the non-solvent below its freezing point or to temperatures where it becomes a poor solvent, the CDP-therapeutic agent conjugate rapidly precipitates in a single step, eliminating the need for multiple decantation and rinsing steps

Inventive Principle:

Principle #36Phase transitions

2Ease of manufacture

If conventional precipitation method is used, then CDP-therapeutic agent conjugates can be isolated, but the precipitated conjugates wrap around mixing impellors and require manual stripping

Engineering Contradiction:

Improveisolation easeVSAvoidmanual operation requirement

Core Design Contradiction:

Ease of manufactureVSEase of operation

Solution Approach 1:

By changing the temperature parameter to sub-ambient levels, the patent alters the physical properties of the precipitated conjugates, causing them to form as free-flowing solids that do not adhere to mixing impellors, thereby eliminating manual stripping requirements

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces the mechanical manual stripping operation with a temperature-based physical chemistry approach. By controlling the precipitation conditions through temperature, the conjugates form in a way that allows automatic filtration and separation, substituting mechanical manual intervention with thermal control

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If conventional precipitation method is used, then CDP-therapeutic agent conjugates can be precipitated, but the process is difficult to reproduce

Engineering Contradiction:

ImprovereproducibilityVSAvoidprocess consistency

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent establishes precise temperature parameters (sub-ambient temperatures such as -70°C to -100°C) as critical process controls. By defining specific temperature ranges and maintaining them throughout the precipitation process, the patent achieves high reproducibility and manufacturing precision that is difficult to achieve with conventional temperature-based methods

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

This method enables efficient precipitation and scaling of CDP-inhibitor conjugates, improving reproducibility and facilitating the generation of nanoparticles for pharmaceutical applications, enhancing treatment options for disorders like proliferative and autoimmune conditions.

Implementation Method 1

introducing a polymer-containing solution into a cooled non-solvent to form a mixture comprising a liquid and the CDP-inhibitor conjugate. The mixture is maintained under conditions to precipitate at least a portion of the CDP-inhibitor conjugate from the mixture

Methodology Applied

Scientific EffectPrecipitation: Precipitation