CA2383955A1 - Extracorporeal endotoxin removal method - Google Patents

Extracorporeal endotoxin removal method Download PDF

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Publication number
CA2383955A1
CA2383955A1 CA002383955A CA2383955A CA2383955A1 CA 2383955 A1 CA2383955 A1 CA 2383955A1 CA 002383955 A CA002383955 A CA 002383955A CA 2383955 A CA2383955 A CA 2383955A CA 2383955 A1 CA2383955 A1 CA 2383955A1
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CA
Canada
Prior art keywords
oligopeptides
adsorbent
polydisperse
arginine
blood
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002383955A
Other languages
French (fr)
Other versions
CA2383955C (en
Inventor
Carl-Martin Bell
Markus Storr
Werner Beck
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gambro Dialysatoren GmbH and Co KG
Original Assignee
Gambro Dialysatoren Gmbh & Co., Kg.
Carl-Martin Bell
Markus Storr
Werner Beck
Gambro Dialysatoren Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gambro Dialysatoren Gmbh & Co., Kg., Carl-Martin Bell, Markus Storr, Werner Beck, Gambro Dialysatoren Gmbh filed Critical Gambro Dialysatoren Gmbh & Co., Kg.
Publication of CA2383955A1 publication Critical patent/CA2383955A1/en
Application granted granted Critical
Publication of CA2383955C publication Critical patent/CA2383955C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D67/00Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
    • B01D67/0081After-treatment of organic or inorganic membranes
    • B01D67/0093Chemical modification
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D71/00Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06Organic material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0011Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using physical methods
    • A61L2/0017Filtration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D61/00Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01DSEPARATION
    • B01D69/00Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/14Dynamic membranes
    • B01D69/141Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30Processes for preparing, regenerating, or reactivating
    • B01J20/32Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3206Organic carriers, supports or substrates
    • B01J20/3208Polymeric carriers, supports or substrates
    • B01J20/321Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30Processes for preparing, regenerating, or reactivating
    • B01J20/32Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3214Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating
    • B01J20/3217Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
    • B01J20/3219Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond involving a particular spacer or linking group, e.g. for attaching an active group
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01JCHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30Processes for preparing, regenerating, or reactivating
    • B01J20/32Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3231Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
    • B01J20/3242Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
    • B01J20/3268Macromolecular compounds
    • B01J20/3272Polymers obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
    • B01J20/3274Proteins, nucleic acids, polysaccharides, antibodies or antigens
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14Extraction; Separation; Purification
    • C07K1/16Extraction; Separation; Purification by chromatography
    • C07K1/22Affinity chromatography or related techniques based upon selective absorption processes
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14Extraction; Separation; Purification
    • C07K1/34Extraction; Separation; Purification by filtration, ultrafiltration or reverse osmosis
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G69/00Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
    • C08G69/02Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
    • C08G69/08Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino-carboxylic acids
    • C08G69/10Alpha-amino-carboxylic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3679Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits by absorption

Abstract

This invention describes blood treating material having the capacity to selectively remove endotoxin and cytokine inducing substances from blood or plasma by extracorporeal adsorption for therapeutic septic shock treatment. The endotoxin adsorption ligands of the invention are oligopeptides synthesized from amino acids having a pk > 7.2 such as arginine, lysine o r histidine, using a polycondensation step such that the resultant oligopeptid es exhibit a high degree of polydispersity. Also provided are methods and devic es using an adsorbent having a polydisperse oligopeptide of the invention immobilized on a solid state support medium for removing endotoxin from the blood of human or animal subject.

Claims (26)

1. A composition consisting essentially of a mixture of linear or branched oligopeptides composed of one or more amino acids having a pK > 7.2, said oligopeptides being polydisperse with respect to molecular weight and to number of branches per molecule.
2. The composition of claim 1 wherein the amino acids are selected from the group consisting of arginine, lysine and histidine.
3. The composition of claim 1 wherein said oligopeptides are polydisperse with an R f value of 0.4 or greater as measured by thin layer chromatography on silica gel using a system of CH3Cl3: CH3OH: NH3/40:40:20 in 45% NH3 solution.
4. The composition of claim 1 wherein said oligopeptides are polydisperse with an R f value of 0.6 or greater as measured by thin layer chromatography on silica gel using a system of CH3Cl3:CH3OH:NH3/40:40:20 in 45%NH3 solution.
5. The composition of claims 1, 2, 3 or 4 wherein the amino acid is arginine.
6. An endotoxin removal adsorbent comprising a ligand immobilized on a solid phase support medium, the ligand consisting essentially of a mixture of linear or branched oligopeptides composed of one or more amino acids having a pK > 7.2, said oligopeptides being polydisperse with respect to molecular weight and to number of branches per molecule.
7. The adsorbent of claim 6 wherein the solid phase support medium is porous sufficient to allow passage of blood cells therethrough.
8. The adsorbent of claim 6 wherein the solid phase support medium is in the form of beads.
9. The adsorbent of claim 6 wherein the ligand is covalently bound to the solid phase support medium.
10. The adsorbent of claims 6, 8 or 9 wherein the amino acid is selected from the group consisting of arginine, lysine and histidine.
11. The adsorbent of claims 8 or 9 wherein said oligopeptides are polydisperse with an R f value of 0.4 or greater as measured by thin layer chromatography on silica gel using a system of CH3Cl3:CH3OH:NH3/40:40:20 in 45% NH3 solution.
12. The adsorbent of claims 8 or 9 wherein said oligopeptides are polydisperse with an R f value of 0.6 or greater as measured by thin layer chromatography on silica gel using a system of CH3Cl3:CH3OH:NH3/40:40:20 in 45% NH3 solution.
13. The adsorbent of claims 8, 9, 11 or 12 wherein the amino acid is arginine.
14. A device for extracorporeal removal of endotoxin from whole blood comprising a container containing and retaining an endotoxin removal adsorbent comprising a ligand immobilized on a solid phase support medium, the ligand consisting essentially of a mixture of linear or branched oligopeptides composed of one or more amino acids having a pK > 7.2, said oligopeptides being polydisperse with respect to molecular weight and to number of branches per molecule, said solid phase support medium being porous sufficient to allow passage of blood cells therethrough, said container having an inlet and an outlet positioned with respect to the adsorbent such that blood entering the inlet contacts the adsorbent before exiting the container through the outlet.
15. The device of claim 14 wherein the solid phase support medium is in the form of beads.
16. The device of claim 15 wherein the ligand is covalently bound to the beads, and the amino acid is selected from the group consisting of arginine, lysine and histidine.
17. The device of claim 14 wherein said oligopeptides are polydisperse with an R f value of 0.4 or greater as measured by thin layer chromatography on silica gel using a system of CH3Cl3:CH3OH:NH3/40:40:20 in 45% NH3 solution.
18. The device of claim 14 wherein said oligopeptides are polydisperse with an R f value of 0.6 or greater as measured by thin layer chromatography on silica gel using a system of CH3Cl3:CH3OH:NH3/40:40:20 in 45% NH3 solution.
19. The device of claims 16, 17 or 18 wherein the amino acid is arginine.
20. A method for removing endotoxin from blood of an animal or human subject comprising removing a portion of blood from the subject, contacting the blood with an adsorbent comprising a ligand immobilized on a solid phase support medium, the ligand consisting essentially of a mixture of linear or branched oligopeptides composed of one or more amino acids having a pK > 7.2, said oligopeptides being polydisperse with respect to molecular weight and to number of branches per molecule, whereby endotoxin is removed from the blood by adsorption to said adsorbent, then returning the blood to the subject.
21. The method of claim 20 wherein the steps of removing, contacting and returning blood are carried out in a continuous flow from and to the subject.
22. The method of claims 20 or 21 wherein the amino acid is selected from the group consisting of arginine, lysine and histidine.
23. The method of claim 22 wherein the amino acid is arginine.
24. A process for making an endotoxin-binding ligand, comprising reacting an amino acid selected from the group consisting of arginine, lysine and histidine with a coupling reagent at a pH selected to provide that a portion of basic groups of the amino acids are unprotonated, whereby a polydisperse, branched oligopeptide mixture is formed.
25. The process of claim 24 wherein the amino acid is arginine, the reaction pH is 12 and the coupling reagent is 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide.
26. An endotoxin-binding ligand made according to the method of claims 24 or 25.
CA2383955A 1999-09-29 2000-09-26 Extracorporeal endotoxin removal method Expired - Fee Related CA2383955C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US15664999P 1999-09-29 1999-09-29
US60/156,649 1999-09-29
US09/677,375 US6774102B1 (en) 1999-09-29 2000-09-15 Extracorporeal endotoxin removal method
US09/677,375 2000-09-15
PCT/IB2000/001364 WO2001023413A1 (en) 1999-09-29 2000-09-26 Extracorporeal endotoxin removal method

Publications (2)

Publication Number Publication Date
CA2383955A1 true CA2383955A1 (en) 2001-04-05
CA2383955C CA2383955C (en) 2010-10-12

Family

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Family Applications (1)

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CA2383955A Expired - Fee Related CA2383955C (en) 1999-09-29 2000-09-26 Extracorporeal endotoxin removal method

Country Status (8)

Country Link
US (1) US6774102B1 (en)
EP (1) EP1220868B1 (en)
JP (1) JP4709452B2 (en)
AT (1) ATE260294T1 (en)
CA (1) CA2383955C (en)
DE (1) DE60008565T2 (en)
ES (1) ES2213604T3 (en)
WO (1) WO2001023413A1 (en)

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Also Published As

Publication number Publication date
ES2213604T3 (en) 2004-09-01
JP4709452B2 (en) 2011-06-22
DE60008565T2 (en) 2004-12-16
CA2383955C (en) 2010-10-12
ATE260294T1 (en) 2004-03-15
WO2001023413A1 (en) 2001-04-05
US6774102B1 (en) 2004-08-10
EP1220868B1 (en) 2004-02-25
JP2003511354A (en) 2003-03-25
DE60008565D1 (en) 2004-04-01
EP1220868A1 (en) 2002-07-10

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