Sorbent for removing protein-bound substances

Patent metadata

Field	Value
Publication number	US-9320845-B2
Application number	US-201013146003-A
Country	US
Kind code	B2
Filing date	Jan 20, 2010
Priority date	Jan 22, 2009
Publication date	Apr 26, 2016
Grant date	Apr 26, 2016

Abstract

The invention relates to a sorption agent having improved selectivity properties for removing protein-bound substances from a biological fluid, in particular blood or blood plasma of patients having severe disturbances of the liver function or liver failure and having kidney insufficiency, thee sorption agent having: (a) a porous, neutral, hydrophobic polymer and (b) a polypeptide layer adsorbed on the polymer, the neutral, hydrophobic polymer having a mean pore size of at least 15 nm. Furthermore, the invention relates to methods and uses in connection with such a sorption agent. The invention is used in particular in extracorporeal liver support.

First claim

The invention claimed is:

1. A sorption agent for removing protein-bound substances from a biological fluid with reduced adsorption of Protein C, the sorption agent comprising:
(a) a porous, neutral, hydrophobic polymer including microparticles, where the microparticles have a particle size of 20 μm or less and
(b) a polypeptide layer adsorbed on the polymer,
wherein the neutral, hydrophobic polymer is a styrene/divinyl benzene copolymer and has a mean pore size of 30-40 nm,
wherein the polypeptide layer comprises at least one type of polypeptide selected from albumin, in particular human albumin, and albumin-like polypeptides, and
wherein a 10% polypeptide solution is used for the adsorptive coating of the neutral, hydrophobic polymer with the polypeptide layer.

2. The sorption agent according to claim 1 , wherein the microparticles have a particle size of 1 to 9 μm.

3. A sorption apparatus for removing protein-bound substances from a biological fluid with reduced adsorption of Protein C, containing a sorption agent comprising:
(a) a porous, neutral, hydrophobic polymer including microparticles, where the microparticles have a particle size of 20 μm or less and
(b) a polypeptide layer adsorbed on the polymer,
wherein the neutral, hydrophobic polymer is a styrene/divinyl benzene copolymer and has a mean pore size of 30-40 nm,
wherein the polypeptide layer comprises at least one type of polypeptide selected from albumin, in particular human albumin, and albumin-like polypeptides, and
wherein a 10% polypeptide solution is used for the adsorptive coating of the neutral, hydrophobic polymer with the polypeptide layer.

4. The sorption apparatus according to claim 3 , wherein the microparticles have a particle size of 1 to 9 μm.

5. A plasma circuit for removing protein-bound substances from a biological fluid with reduced adsorption of Protein C, containing a suspension of a sorption agent comprising:
(a) a porous, neutral, hydrophobic polymer including microparticles, where the microparticles have a particle size of 20 μm or less and
(b) a polypeptide layer adsorbed on the polymer,
wherein the neutral, hydrophobic polymer is a styrene/divinyl benzene copolymer and has a mean pore size of 30-40 nm,
wherein the polypeptide layer comprises at least one type of polypeptide selected from albumin, in particular human albumin, and albumin-like polypeptides,
wherein a 10% polypeptide solution is used for the adsorptive coating of the neutral, hydrophobic polymer with the polypeptide layer.

6. The plasma circuit according to claim 5 , wherein the microparticles have a particle size of 1 to 9 μm.

7. A method for producing a sorption agent comprising:
adsorptive coating a porous, neutral hydrophobic polymer with a polypeptide layer using a polypeptide solution, where the sorption agent comprises:
(a) the porous, neutral, hydrophobic polymer including microparticles, where the microparticles have a particle size of 20 μm or less and
(b) the polypeptide layer is adsorbed on the polymer,
wherein the neutral, hydrophobic polymer is a styrene/divinyl benzene copolymer and has a mean pore size of 30-40 nm,
wherein the polypeptide layer comprises at least one type of polypeptide selected from albumin, in particular human albumin, and albumin-like polypeptides, and
wherein the polypeptide solution is a 10% polypeptide solution.

8. The method according to claim 7 , wherein the microparticles have a particle size of 1 to 9 μm.

9. A method for removing protein-bound substances from a biological fluid, comprising:
bringing a biological fluid containing protein-bound substances into contact with a sorption agent, where the sorption agent comprises:
(a) a porous, neutral, hydrophobic polymer including microparticles, where the microparticles have a particle size of 20 μm or less and
(b) a polypeptide layer adsorbed on the polymer,
wherein the neutral, hydrophobic polymer is a styrene/divinyl benzene copolymer and has a mean pore size of 30-40 nm,
wherein the polypeptide layer comprises at least one type of polypeptide selected from albumin, in particular human albumin, and albumin-like polypeptides, and
wherein a 10% polypeptide solution is used for an adsorptive coating of the neutral, hydrophobic polymer with the polypeptide layer.

10. The method according to claim 9 , wherein the biological fluid is blood or blood plasma.

11. The method according to claim 9 , where the protein-bound substances particularly being bilirubin, aromatic amino acids, bile acids, phenols, and mercaptans.

12. The method according to claim 9 , wherein the selective sorption agent is used for removing protein-bound substances from blood plasma.

13. The method according to claim 9 , wherein the selective sorption agent is used for removing protein-bound substances from blood.

14. The method according to claim 9 , wherein the selective sorption agent is used in an MDS (Microsphere-based Detoxification System).

15. The method according to claim 9 , wherein the microparticles have a particle size of 1 to 9 μm.

Assignees

• Falkenhagen Dieter
• Hartmann Jens
• Weber Viktoria
• Fresenius Medical Care De Gmbh

Inventors

• Falkenhagen Dieter
• Hartmann Jens
• Weber Viktoria

Classifications

• B01J20/3253

  comprising a cyclic structure not containing any of the heteroatoms nitrogen, oxygen or sulfur, e.g. aromatic structures · CPC title

• B01J20/264

  derived from different types of monomers, e.g. linear or branched copolymers, block copolymers, graft copolymers · CPC title

• B01J20/321

  consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds · CPC title

• B01J20/28083

  being in the range 2-50 nm, i.e. mesopores · CPC title

• A61M1/3679 Primary

  by absorption (A61M1/3675 takes precedence) · CPC title