Hemocompatible adsorber for the dialysis of protein-bound uremic toxins

Patent metadata

Field	Value
Publication number	US-10625241-B2
Application number	US-201815969306-A
Country	US
Kind code	B2
Filing date	May 2, 2018
Priority date	Jun 22, 2017
Publication date	Apr 21, 2020
Grant date	Apr 21, 2020

Abstract

A hemocompatible adsorber for separating protein-bound uremic toxins contained in the blood of a patient and having a molecular mass of <500 g/mol regarding their carrier proteins, to adsorb the uremic toxins during hemodialysis. The hemocompatible adsorber including a polymer based on a cyclic oligosaccharide or a derivative thereof which is disposed on a solid carrier component. A device for hemodiafiltration including an extracorporeal circuit for receiving blood to be purified and a hemodialyzer connected to the blood circulation of a patient, wherein a hemocompatible adsorber is provided for separating protein-bound uremic toxins contained in the blood of a patient and having a molecular mass of <500 g/mol regarding their carrier proteins. The hemocompatible adsorber, which is disposed on a solid carrier component in at least one layer on the blood side within the hemodialyzer, includes a polymer based on a cyclic oligosaccharide or a derivative thereof.

First claim

The invention claimed is:

1. A hemodiafiltration apparatus comprising:
an extracorporeal circuit for receiving blood to be purified;
at least one of a hemodialyzer or hemofilter connected to the blood circulation of a patient; and
a hemocompatible adsorber for separating protein-bound uremic toxins contained in the blood or blood plasma of the patient and having a molecular mass of <500 g/mol regarding their carrier proteins;
wherein the hemocompatible adsorber, which is disposed on a solid carrier component in at least one layer on a blood side within the hemodialyzer or hemofilter, comprises a polymer based on a cyclic oligosaccharide or a derivative thereof,
wherein the polymer is disposed on the solid carrier component using a layer by layer (LBL) technology,
wherein the polymer for a first layer of the LBL technology is an anionic polyelectrolyte,
wherein the polymer for a second layer disposed on the first layer is a cationic counterpart, and
wherein the hemocompatible adsorber is integrated as the solid carrier component coated with the polymer in a blood cap of the hemodialyzer.

2. The hemodiafiltration apparatus according to claim 1 , wherein the uremic toxins are selected from the group consisting of p-cresol, indoxyl sulfate, phenol, phenol derivatives, homocysteine, urofuranic acids, in particular 3-carboxy-4-methyl-5-propyl-2-furanopropionic acid, hippuric acid and p-hydroxyhippuric acid.

3. The hemodiafiltration apparatus according to claim 1 , wherein the carrier protein is human albumin.

4. The hemodiafiltration apparatus according to claim 1 , wherein the polymer based on cyclic oligosaccharides is selected from the group consisting of: polycyclodextrins, poly-β-cyclodextrins, poly(carboxymethyl-β-cyclodextrin) and poly(trimethylammonium-β-cyclodextrin) or their derivatives and cyclodextrins fused with epichlorohydrin.

5. The hemodiafiltration apparatus according to claim 1 , wherein the solid carrier component is selected from the group consisting of: a preferably non-woven fabric material, a hollow fiber or flat membrane or other porous materials based on polyether sulfone [PES], polysulfone [PSU], polyether ether ketones [PEEK], polyphenylsulfone [PPSU], polyoxymethylene [POM], polyphenol, polyamides, in particular nylon, polystyrene, polyacrylate, polycarbonate or polymers containing acrylonitrile or a methylallylsulfonate salt or copolymers thereof.

6. The hemodiafiltration apparatus according to claim 1 , wherein the solid carrier component is a porous material based on polyethersulfone [PES], polysulfone [PSU], polyether ether ketones [PEEK], polyphenylsulfone [PPSU], polyoxymethylene [POM], polyphenol, polyamides, in particular nylon, polystyrene, polyacrylate, polycarbonate or polymers containing acrylonitrile or a methylallylsulfonate salt or copolymers thereof.

7. The hemodiafiltration apparatus according to claim 1 , wherein the anionic polyelectrolyte is poly(carboxymethyl-β-cyclodextrin).

8. The hemodiafiltration apparatus according to claim 1 , wherein the cationic counterpart is polyethylene imine or poly(trimethylammonium-6-cyclodextrin).

9. A hemodiafiltration apparatus comprising:
an extracorporeal circuit for receiving blood to be purified;
at least one of a hemodialyzer or hemofilter connected to the blood circulation of a patient; and
a hemocompatible adsorber for separating protein-bound uremic toxins contained in the blood or blood plasma of the patient and having a molecular mass of <500 g/mol regarding their carrier proteins;
wherein the hemocompatible adsorber, which is disposed on a solid carrier component in at least one layer on a blood side within the hemodialyzer or hemofilter, comprises a polymer based on a cyclic oligosaccharide or a derivative thereof,
wherein the polymer is disposed on the solid carrier component using a layer by layer (LBL) technology,
wherein the polymer for a first layer of the LBL technology is an anionic polyelectrolyte,
wherein the polymer for a second layer disposed on the first layer is a cationic counterpart, and
wherein the hemocompatible adsorber is integrated into a pore system of hollow fiber membranes of the hemodialyzer.

10. The hemodiafiltration apparatus according to claim 9 , wherein the anionic polyelectrolyte is poly(carboxymethyl-β-cyclodextrin).

11. The hemodiafiltration apparatus according to claim 9 , wherein the cationic counterpart is polyethylene imine or poly(trimethylammonium-6-cyclodextrin).

12. The hemodiafiltration apparatus according to claim 9 , wherein the uremic toxins are selected from the group consisting of p-cresol, indoxyl sulfate, phenol, phenol derivatives, homocysteine, urofuranic acids, in particular 3-carboxy-4-methyl-5-propyl-2-furanopropionic acid, hippuric acid and p-hydroxyhippuric acid.

13. The hemodiafiltration apparatus according to claim 9 , wherein the carrier protein is human albumin.

14. The hemodiafiltration apparatus according to claim 9 , wherein the polymer based on cyclic oligosaccharides is selected from the group consisting of: polycyclodextrins, poly-β-cyclodextrins, poly(carboxymethyl-β-cyclodextrin) and poly(trimethylammonium-β-cyclodextrin) or their derivatives and cyclodextrins fused with epichlorohydrin.

15. The hemodiafiltration apparatus according to claim 9 , wherein the solid carrier component is selected from the group consisting of: a preferably non-woven fabric material, a hollow fiber or flat membrane or other porous materials based on polyether sulfone [PES], polysulfone [PSU], polyether ether ketones [PEEK], polyphenylsulfone [PPSU], polyoxymethylene [POM], polyphenol, polyamides, in particular nylon, polystyrene, polyacrylate, polycarbonate or polymers containing acrylonitrile or a methylallylsulfonate salt or copolymers thereof.

16. The hemodiafiltration apparatus according to claim 9 , wherein the solid carrier component is a porous material based on polyethersulfone [PES], polysulfone [PSU], polyether ether ketones [PEEK], polyphenylsulfone [PPSU], polyoxymethylene [POM], polyphenol, polyamides, in particular nylon, polystyrene, polyacrylate, polycarbonate or polymers containing acrylonitrile or a methylallylsulfonate salt or copolymers thereof.

Assignees

• Braun Avitum Ag

Inventors

• Baier-Goschütz Angela
• Friebe Alexander
• Napierala Roland
• Gäbler Juliane

Classifications

• B01J20/321

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

• B01J20/267

  Cross-linked polymers · CPC title

• A61M1/1621

  Constructional aspects thereof (semi-permeable membranes for separation processes characterised by their properties B01D69/00; semi permeable membranes characterised by their material B01D71/00) · CPC title

• B01J20/22

  comprising organic material · CPC title

• B01J20/28035

  with more than one layer, e.g. laminates, separated sheets · CPC title