Size-Selective Hemoperfusion Adsorbents for Midsize Protein Removal

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Solution Overview

Problem

Conventional adsorbents used in hemoperfusion and plasma perfusion lack selectivity for midsize proteins like β 2 -microglobulin and cytokines, often adsorbing both toxins and beneficial proteins, which can lead to side effects and complications in long-term clinical treatments.

Innovation Solution

Development of size-selective porous polymeric adsorbents with pore diameters ranging from 75 to 300 Angstroms, specifically designed to adsorb small to midsize protein molecules (≤50,000 Daltons) while excluding larger proteins, using macroreticular synthesis and aromatic monomers with crosslinking agents like divinylbenzene, and hemocompatible surface coatings to ensure biocompatibility and selectivity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional adsorbents are used in hemoperfusion, then adsorption capacity is achieved, but selectivity for midsize proteins is lost and beneficial proteins are also adsorbed

Engineering Contradiction:
Improveadsorption capacityVSAvoidnonselective adsorption of beneficial proteins
Core Design Contradiction:
Quantity of substanceVSObject-generated harmful factors

Solution Approach 1:

The patent employs porous polymeric beads with specifically controlled pore sizes (75-300 Angstroms) to achieve size-selective adsorption. The pore structure allows midsize proteins like beta-2-microglobulin to enter and be adsorbed while excluding larger beneficial proteins, thus resolving the contradiction between adsorption capacity and selectivity

Inventive Principle:
Principle #31Porous materials

Solution Approach 2:

The patent changes the physical parameter of pore size to achieve selectivity. By controlling the pore diameter within a specific range (75-300 Angstroms), the adsorbent can discriminate between different protein sizes, allowing toxic midsize proteins to be adsorbed while larger beneficial proteins are excluded

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If adsorbents with large pore surface are used, then adsorption capacity increases, but selectivity decreases due to broad pore size distribution

Engineering Contradiction:
Improveadsorption capacityVSAvoidpore size distribution control
Core Design Contradiction:
Quantity of substanceVSManufacturing precision

Solution Approach 1:

The patent precisely controls the pore size parameter within a narrow range (75-300 Angstroms) to achieve both high adsorption capacity and high selectivity. This controlled parameter approach allows the adsorbent to maintain large surface area while ensuring uniform pore sizes that provide size-selective adsorption

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates uniform pore structures throughout the adsorbent material with consistent pore sizes in the 75-300 Angstroms range. This local uniformity in pore quality ensures that all regions of the adsorbent provide the same size-selective adsorption characteristics, resolving the contradiction between capacity and selectivity

Inventive Principle:
Principle #3Local quality

3Quantity of substance

If hydrophobic adsorbents are used for high adsorption capacity, then hemocompatibility decreases

Engineering Contradiction:
Improveadsorption capacityVSAvoidhemocompatibility
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent uses composite polymeric materials that combine hydrophobic regions (for adsorption capacity) with hydrophilic surface characteristics (for hemocompatibility). The porous polymeric structure provides both the adsorption capacity needed for toxin removal and the biocompatible properties required for clinical use

Inventive Principle:
Principle #40Composite materials

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 adsorbents effectively remove β 2 -microglobulin and cytokines from blood while maintaining clinically acceptable levels of albumin, immunoglobulins, and other essential blood components, providing a safe and effective long-term treatment option for patients.

Implementation Method 1

These adsorbents are useful in conjunction with hemodialysis for extracting and controlling the blood level of β 2 -microglobulin... Hemoperfusion is passing whole blood over an adsorbent to remove contaminants from the blood

Methodology Applied
Scientific EffectAdsorption: Adsorption

Implementation Method 2

size-selective porous polymeric adsorbents with pore diameters ranging from 75 to 300 Angstroms, specifically designed to adsorb small to midsize protein molecules (≤50,000 Daltons) while excluding larger proteins

Methodology Applied
Scientific EffectSize-selective separation: Filter (physical)

Data Source

PatentEP2155285B1Size-selective hemoperfusion polymeric adsorbents
Publication Date: 2021.06.23 CYTOSORBENTS CORP
  • EP2155285B1 patent drawingFigure 1

AI summary

Size-selective hemocompatible porous polymeric adsorbents are provided with a pore structure capable of excluding molecules larger than 50,000 Daltons, but with a pore system that allows good ingress and egress of molecules smaller than 35,000 Daltons. The pore system in these porous polymeric adsorbents is controlled by the method of synthesis so that 98% of the total pore volume is located in pores smaller than 300 Angstroms in diameter with a working pore size range within 100 to 300 Angstroms in diameter. The porous polymeric adsorbents of this invention are very selective for extracting midsize proteins, such as cytokines and β2-microglobulin, from blood and other physiologic fluids while keeping the components required for good health such as cells, platelets, albumin, hemoglobin, fibrinogen, and other serum proteins intact.