Extracorporeal stablised expanded bed adsorption method for the treatment of sepsis

• US 20050249724A1
• Filed: 07/09/2003
• Published: 11/10/2005
• Est. Priority Date: 07/11/2002
• Status: Abandoned Application

• Current Assignee: Upfront Chromatography A/S
• Original Assignee: Upfront Chromatography A/S
• Inventors: Heegaard, Peter M.H., Lihme, Allan Otto Fog
• Application Number:
  US10/520,685
• Publication Number:
  US 20050249724A1
• Time in Patent Office: Days
• US Class Current: 424/140.100
• CPC Class Codes: A61M 1/3681 by irradiation
• CPC Class Codes: B01D 15/1807 using counter-currents, e.g. fluidised beds
• CPC Class Codes: B01D 15/3804 Affinity chromatography
• CPC Class Codes: B01J 20/262 obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. obtained by polycondensation macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds per se C08G
• CPC Class Codes: B01J 20/264 derived from different types of monomers, e.g. linear or branched copolymers, block copolymers, graft copolymers
• CPC Class Codes: B01J 20/267 Cross-linked polymers
• CPC Class Codes: B01J 20/28019 Spherical, ellipsoidal or cylindrical
• CPC Class Codes: B01J 20/28061 being in the range 100-500 m2/g
• CPC Class Codes: B01J 20/286 Phases chemically bonded to a substrate, e.g. to silica or to polymers
• CPC Class Codes: B01J 20/3092 Packing of a container, e.g. packing a cartridge or column of chromatography columns B01D15/206
• CPC Class Codes: B01J 20/3212 consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3217 Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
• CPC Class Codes: B01J 20/3219 involving a particular spacer or linking group, e.g. for attaching an active group
• CPC Class Codes: B01J 20/3251 comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
• CPC Class Codes: B01J 20/3255 comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. heterocyclic or heteroaromatic structures
• CPC Class Codes: B01J 20/3272 Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3274 Proteins, nucleic acids, polysaccharides, antibodies or antigens
• CPC Class Codes: B01J 20/3289 Coatings involving more than one layer of same or different nature
• CPC Class Codes: B01J 20/3293 Coatings on a core, the core being particle or fiber shaped, e.g. encapsulated particles, coated fibers
• CPC Class Codes: B01J 2220/54 Sorbents specially adapted for analytical or investigative chromatography
• CPC Class Codes: B01J 2220/56 : Use in the form of a bed
• CPC Class Codes: B01J 2220/58 : Use in a single column

Abstract

The present invention provides an extracorporeal adsorption method for removing harmful substances from blood in a way that is practicable in everyday clinical practice and applicable for the timely intervention to present the development of sepsis. Said extracorporeal adsorption method being effected by an adsorption column assembly where the adsorption column assembly comprising a column and an adsorption medium in the form of particles. The sedimented volume of said particles being at the most 80% of the volume of the column.

Claims

1. An extracorporeal adsorption method for removing harmful substances responsible of inducing sepsis caused by Gram-negative in a mammal, said extracorporeal adsorption method being effected by an adsorption column assembly, said adsorption column assembly comprising a column and an adsorption medium in the form of particles, the sedimented volume of said particles being at the most 80% of the volume of the column, said particles being characterised by carrying an affinity specific molecule with a specific affinity for the LPS portion of said Gram-negative bacteria, said method comprising treating blood obtained from said mammal by passing the blood through the adsorption column assembly at such a flow rate that a fluidised bed of the particles is formed.

3. A method according to claim 1 wherein the treated blood is capable of being reinfused into the same mammal.

4. A method according to claim 1, wherein the adsorption column assembly is adapted for fluidised bed adsorption, in particular stabilised fluidised bed adsorption.

5. A method according to claim 1, wherein the particles have a density of at least 1.3 g/ml and a mean diameter in the range of 5-1000 μ

m, such as a density of at least 1.5 g/ml and a mean diameter in the range of 5-300 μ

m, preferably a density of at least 1.8 g/ml and a mean diameter in the range of 5-150 μ

m, and most preferred a density of more than 2.5 g/ml and a mean diameter in the range of 5-75 μ

m.

6. A method according to claim 1, wherein the mammal is a human being.

7. A method according to claim 1, wherein the affinity specific molecule is selected from the group consisting of immunoglobulins, peptides, oligonucleotides, receptor proteins, antibiotics, and lectins.

8. A method according to claim 1, wherein two or more different affinity specific molecules are present on particles within the adsorption medium.

9. A method according to claim 6, wherein the affinity specific molecules are selected from immunoglobulins.

10. A method according to claim 1, wherein the affinity specific molecule is Polymyxin B.

11. A method according to claim 1, wherein the affinity specific molecule is selected from the group consisting of a Toll-like receptor, most preferably TLR4 or binding fragments thereof or multimeric arrangements thereof, CD14, MD2, TLR2 and LBP, and any combination thereof.

12. A method according to claim 1, wherein the sedimented volume of the particles is at the most 70% of the volume of the column, such as at the most 60% of the volume of the column, e.g. at the most 50% of the volume of the column.

16. The use according to claim 12, wherein the steps (a), (b) and (c) are preceded by a initial step by which a substance is first injected into the blood stream of the mammal.

19. A use according to claim 11, wherein the stabilised fluidised bed is placed in line with a switch capable of being activated when a blood substance reaches a pre-set value, said blood substance is monitored by a device, said device is placed in line with the blood circulation, said device sending the activating signal to the switch when said value is reached.

2. An extracorporeal adsorption method for removing harmful substances responsible of inducing sepsis caused by Gram-negative or Gram-positive bacteria in a mammal, said extracorporeal adsorption method being effected by an adsorption column assembly, said adsorption column assembly comprising a column and an adsorption medium in the form of particles, the sedimented volume of said particles being at the most 80% of the volume of the column, said particles being characterised by carrying an affinity specific molecule with a specific affinity for:

i) the LPS portion of said Gram-negative bacteria, and/or

ii) Gram-positive bacteria or harmful substances derived from said Gram-positive bacteria, said method comprising treating blood obtained from said mammal by passing the blood through the adsorption column assembly at such a flow rate that a fluidised bed of the particles is formed.

13. Use of an adsorption medium for the preparation of a therapeutic adsorption column assembly for the continues therapeutic treatment of sepsis caused by Gram-negative bacteria in a mammal by extracorporeal adsorption, said adsorption column assembly comprising (i) a vessel for continues obtaining blood from said mammal, (ii) a column comprising the adsorption medium, the sedimented volume of said adsorption medium being at the most 80% of the volume of the column, said adsorption medium being characterised by carrying an affinity specific molecule with a specific affinity for the LPS portion of said Gram-negative bacteria, said column is treating the obtained blood by passing the blood through the adsorption column assembly at such a flow rate that a fluidised bed of the adsorption medium is formed, and (iii) another vessel which continuously delivers blood back to the patient.

15. The use according claim 13, wherein the flow rate of the blood through the column assembly is such that expansion ratio of the fluidised bed is at least 1.3, such as at least 1.5.

17. The use according to claim 13, wherein the mammal is a human being.

18. The use according to claim 13, wherein the particles have a density of at least 1.3 g/ml and a mean diameter in the range of 5-1000 μ

m, such as a density of at least 1.5 g/ml and a mean diameter in the range of 5-300 μ

m, preferably a density of at least 1.8 g/ml and a mean diameter in the range of 5-150 μ

m, and most preferred a density of more than 2.5 g/ml and a mean diameter in the range of 5-75 μ

m.

20. The use according to claim 13, wherein the affinity specific molecule is selected from the group consisting of immunoglobulins, peptides, oligonucleotides, receptor proteins, antibiotics, and lectins.

21. The use according to claim 13, wherein two or more different affinity specific molecules are present on particles within the adsorption medium.

22. The use according to claim 20, wherein the affinity specific molecules are selected from immunoglobulins.

23. The use according to claim 20, wherein the affinity specific molecule is Polymyxin B.

24. A use according to claim 13, wherein the affinity specific molecule is selected from the group consisting of a Toll-like receptor, most preferably TLR4 or binding fragments thereof or multimeric arrangements thereof, CD14, MD2, TLR2 and LBP, and any combination thereof.

25. The use according to claim 13, wherein the sedimented volume of the particles is at the most 70% of the volume of the column, such as at the most 60% of the volume of the column, e.g. at the most 50% of the volume of the column.

26. The use according to claim 13, wherein the flow rate is such that stabilised fluidised bed of the particles is formed.

14. Use of an adsorption medium for the preparation of a therapeutic adsorption column assembly for the therapeutic treatment of sepsis caused by Gram-negative or Gram-postive bacteria in a mammal by extracorporeal adsorption, said adsorption column assembly comprising (a) a vessel for continuos obtaining blood from said mammal, (b) a column and the adsorption medium, the sedimented volume of said adsorption medium being at the most 80% of the volume of the column, said adsorption medium being characterised by carrying an affinity specific molecule with a specific affinity for:

i) the LPS portion of said Gram-negative bacteria, and/or

ii) Gram-positive bacteria or harmful substances derived from said Gram-positive bacteria, said column is treating the obtained blood by passing the blood through the adsorption column assembly at such a flow rate that a fluidised bed of the adsorption medium is formed, and

(c) another vessel which continuously delivers blood back to the patient.