Immunoglobulin adsorbent and adsorption apparatus

• US 4,705,628 A
• Filed: 04/07/1986
• Issued: 11/10/1987
• Est. Priority Date: 04/09/1985
• Status: Expired due to Fees

• Current Assignee: Terumo Kabushiki Kaisha T
• Original Assignee: Terumo Kabushiki Kaisha
• Inventors: Yamamoto, Yuichi, Sameshima, Tadashi
• Primary Examiner(s): Fisher, Richard V.
• Assistant Examiner(s): JONES, WILLIAM G
• Application Number:
  US06/849,068
• Time in Patent Office: 582 Days
• Field of Search: 436/524, 436/527, 436/532, 502/402, 548/197, 548/246, 548/138, 210/287, 210/289, 210/502.1, 210/927, 210/506, 210/908
• US Class Current: 210/289
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 2202/0057 retained by adsorption
• CPC Class Codes: A61M 2202/0417 Immunoglobulin
• CPC Class Codes: B01J 20/3263 comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. an heterocyclic or heteroaromatic structure
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: G01N 33/552 Glass or silica
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9

Abstract

For the treatment of various diseases including autoimmune diseases such as myathenia gravis, articular rhematism, lupus erythematosus, etc., immunity-related diseases such as glumerulonephritis, bronchial asthma, polyneuritis, etc., organ transplantation such as transplanted kidney rejection, AOB incompatibility bone marrow transplantation, etc., tumor, hypertension, and hepatic insufficiency, immunoglobulin adsorbents comprising a hydroxyl-containing water-insoluble carrier to which a diamine compound having the general formula:

NH.sub.2 (CH.sub.2).sub.n NH.sub.2

wherein n is an integer having a value of 3 to 9 is attached through a silane coupling agent or a derivative thereof, to which diamine a heterocyclic compound is attached through a difunctional reagent, are useful as they can selectively and efficiently adsorb specific proteins such as immunoglobulins and immune complexes which are pathogenic substances in the diseases, exhibit minimized non-specific adsorption, and are safe and easy to sterilize.

Claims

1. An apparatus for adsorbing an immunoglobulin in a body fluid comprising

a vessel having an inlet and an outlet for passing body fluid therethrough,

an adsorbent for an immunogloblin charged in said vessel, said adsorbent comprising a hydroxyl-containing water-insoluble carrier to which a diamine compound having the general formula:

space="preserve" listing-type="equation">NH.sub.2 (CH.sub.2).sub.n NH.sub.2

wherein n is an integer having a value of 3 to 9 is attached through a silane coupling agent or a derivative thereof, a heterocyclic compound being attached to the amine through a difunctional reagent, and

means for preventing the adsorbent from flowing out of said vessel.

2. The adsorbent of claim 1 wherein the diamine compound is selected from the group consisting of 1,3-propanediamine, 1,6-hexanediamine, and 1,9-diaminononane.

3. The adsorbent of claim 1 wherein the diamine compound has a length of from about 5 to about 20 angstrom.

4. The adsorbent of claim 1 wherein the total length of the silane coupling agent, the diamine compound, and the heterocyclic compound ranges from about 40 to about 55 angstrom.

5. The adsorption apparatus of claim 1 wherein said means comprises a filter disposed in said vessel.

6. An adsorbent for an immunoglobulin comprising a hydroxyl-containing water-insoluble carrier to which a diamine compound having the general formula:

space="preserve" listing-type="equation">NH.sub.2 (CH.sub.2).sub.n NH.sub.2

wherein n is an integer having a value of 3 to 9 is attached through a silane coupling agent or a derivative thereof, wherein a heterocyclic compound is attached to the diamine through a difunctional reagent, wherein the total length of the silane coupling agent, the diamine compound, the difunctional reagent and the heterocyclic compound ranges from about 40 to about 55 angstrom.

7. The adsorbent of claim 6 wherein the diamine compound is selected from the group consisting of 1,3-propanediamine, 1,6-hexanediamine, and 1,9-diaminononane.

8. The adsorbent of claim 6 wherein the diamine compound has a length of from about 5 to about 20 angstrom.

9. The adsorbent of claim 6 wherein said difunctional reagent is a difunctional reagent capable of bonding amino groups with each other and said heterocyclic compound has an amino group or an amino group incorporated therein.

10. The adsorbent of claim 6 wherein said heterocyclic compound is a sulfa drug in the form of a sulfonamide.

11. The adsorbent of claim 6 wherein said silane coupling agent is selected from the group consisting of γ

-glycidoxypropyltrimethoxysilane, γ

-glycidoxypropylmethyldiethoxysilane, β

-(3,4-epoxycyclohexyl)ethyltrimethoxysilane, γ

-aminopropyltriethoxysilane, and N-β

(aminoethyl)-γ

-aminopropyltrimethoxysilane.

12. The adsorbent of claim 6 wherein said difunctional reagent is selected from the group consisting of dialdeydes, bisepoxides, alkylimide esters, and diisocyanates.

13. The adsorbent of claim 12 wherein said difunctional reagent is glutaraldehyde.

14. The adsorbent of claim 6 wherein said water-insoluble carrier is comprised of a porous inorganic material predominantly comprising silicon dioxide and having a silanol group.

15. The adsorbent of claim 14 wherein said water-insoluble carrier is in the form of particles having a particle diameter in the range between 0.05 mm and 5 mm.

16. The adsorbent of claim 14 wherein said water-insoluble carrier has a mean pore diameter between 1000 angstrom and 5000 angstrom.

17. An adsorbent for an immunoglobulin comprising a hydroxyl-containing water-insoluble carrier to which a diamine compound having the general formula:

space="preserve" listing-type="equation">NH.sub.2 (CH.sub.2).sub.n NH.sub.2

wherein n is an integer having a value of 3 to 9 is attached through a silane coupling agent or a derivative thereof, wherein a heterocyclic compound is attached to the diamine through a difunctional agent, wherein said heterocyclic compound is a sulfa drug, said sulfa drug being selected from the group consisting of sulfathiazole, sulfamethizole and sulfisomezole.