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Last Updated: March 28, 2024

Claims for Patent: 4,246,351


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Summary for Patent: 4,246,351
Title: Protein adsorbent
Abstract:A novel protein adsorbent consisting essentially of a porous copolymer obtained by copolymerizing a monomer mixture comprising at least one cyano group-containing monomer and at least one cross-linkable monomer, said copolymer having an average pore diameter (d) of from 40 A to 9,000 A and a total pore volume of from 0.05.sqroot.X ml to 1.5.sqroot.X ml per gram of the copolymer in a dry state, in which X designates the weight proportion of said cross-linkable monomer expressed in terms of the percent by weight based on the total monomers. The present porous copolymer adsorbent has a remarkably high protein adsorbing capacity. The adorbent can advantageously be used for various purposes such as purification and separation of proteins, and removal of proteins. Copolymer-protein composites obtained by adsorption of proteins on the present porous copolymer also are industrially useful and have a wide variety of applications.
Inventor(s): Miyake; Tetsuya (Tokyo, JP), Takeda; Kunihiko (Yokohama, JP), Ikeda; Akihiko (Yokohama, JP), Mizuno; Masayuki (Nobeoka, JP)
Assignee: Asahi Kasei Kogyo Kabushiki Kaisha (Osaka, JP)
Application Number:06/088,927
Patent Claims:1. A method for adsorbing a protein from an aqueous solution or dispersion of the protein which comprises contacting an aqueous solution or a dispersion of a protein with a porous copolymer obtained by copolymerizing a monomer mixture comprising 2 to 98% by weight of at least one cyano group-containing monomer represented by the following general formula (A): ##STR6## wherein R stands for a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a halogen atom, a cyano group, a methoxy group, an acetoxyl group, or an unsubstituted or substituted phenyl group represented by the formula ##STR7## wherein R' stands for a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a halogen atom, a cyano group, a methoxy group or an acetoxyl group), and 2 to 98% by weight of at least one cross-linkable monomer having a plurality of CH.sub.2 .dbd.C< groups, said copolymer having an average pore diameter (d) of from 40 A to 9,000 A and a total pore volume of from 0.05 .sqroot.X ml to 1.5 .sqroot.X ml per gram of the copolymer in a dry state, in which X designates the weight proportion of said cross-linkable monomer expressed in terms of the percent by weight based on the total monomers, and being employed in an amount of 0.02 to 300 g per liter of said solution or said dispersion.

2. A method as set forth in claim 1 wherein the contacting of said solution or said dispersion with said porous copolymer is batchwise effected.

3. A method as set forth in claim 1 wherein the contacting of said solution or said dispersion with said porous copolymer is continuously effected.

4. A method as set forth in claim 1 wherein the contacting of said solution or said dispersion with said porous copolymer is effected at a temperature in the range of from 2.degree. C. to 95.degree. C.

5. A method as set forth in claim 2 wherein the contacting time is in the range of from 10 seconds to 500 hours.

6. A method as set forth in claim 3 wherein said solution or said dispersion is supplied at a space velocity in the range of from 0.01 hr.sup.-1 to 1,000 hr.sup.-1.

7. A method as set forth in claim 1 wherein said solution or said dispersion has a pH of from 1 to 11.

8. A composite comprising a porous copolymer and a protein in an amount sufficient to exert activity of said protein adsorbed thereon, said porous copolymer being a product obtained by copolymerizing a monomer mixture comprising 2 to 98% by weight of at least one cyano group-containing monomer represented by the following general formula (A): ##STR8## wherein R stands for a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a halogen atom, a cyano group, a methoxy group, an acetoxyl group, or an unsubstituted or substituted phenyl group represented by the formula ##STR9## (wherein R' stands for a hydrogen atom, an alkyl group having 1 to 10 carbon atoms, a halogen atom, a cyano group, a methoxy group or an acetoxyl group), and 2 to 98% by weight of at least one cross-linkable monomer having a plurality of CH.sub.2 .dbd.C< groups, said copolymer having an average pore diameter (d) of from 40 A to 9,000 A and a total pore volume of from 0.05 .sqroot.X ml to 1.5 .sqroot.X ml per gram of the copolymer in a dry state, in which X designates the weight proportion of said crosslinkable monomer expressed in terms of the percent by weight based on the total monomers.

9. A composite as set forth in claim 8 wherein the amount of the protein is at least 10 mg per gram of the copolymer in a dry state.

10. A composite as set forth in claim 9 wherein the amount of the protein is at least 20 mg per gram of the copolymer in a dry state.

11. A composite as set forth in claim 8, wherein the protein is an enzyme.

12. A method as set forth in claim 1 wherein the content of the cyano group-containing monomer is 4 to 95% by weight.

13. A method as set forth in claim 1 wherein the content of the cyano group-containing monomer is 6 to 90% by weight.

14. A method as set forth in claim 1 wherein the cyano group-containing monomer is a member selected from the group consisting of acrylonitrile, methacrylonitrile and mixtures thereof.

15. A method as set forth in claim 1 wherein the cross-linkable monomer is a monomer having 2 to 4 vinyl groups.

16. A method as set forth in claim 1 wherein the cross-linkable monomer is divinylbenzene.

17. A method as set forth in claim 1 wherein the cross-linkable monomer is of the formula ##STR10## wherein R.sub.1 and R.sub.2 each independently is hydrogen or methyl, and n is an integer from 1 to 30.

18. A method as set forth in claim 1 wherein the weight proportion of the cross-linkable monomer is 8 to 80% by weight.

19. A method as set forth in claim 1 wherein the average pore diameter (d) of said porous copolymer is in the range of from 50 A to 5,000 A.

20. A method as set forth in claim 1 wherein the volume of pores of said porous copolymer having a diameter of 0.5 d to 2 d is not more than 60% of the total pore volume.

21. A method as set forth in claim 1 wherein the total pore volume of said porous copolymer is in the range of from 0.2 .sqroot.X ml to 1.3 .sqroot.X ml per gram of the copolymer in a dry state.

22. A method as set forth in claim 1 wherein the protein has a molecular weight of from 1,000 to 1,000,000.

23. A method as set forth in claim 1 wherein the protein is albumin of human serum.

24. A method as set forth in claim 1 wherein the protein is .alpha.-chymotrypsin.

25. A method as set forth in claim 1 wherein the protein is lipase.

26. A method as set forth in claim 1 wherein the protein is an enzyme.

27. A method as set forth in claim 1 wherein the protein is trypsin.

28. A method as set forth in claim 1 wherein the protein is chymotrypsin.

29. A method as set forth in claim 1 wherein the protein is an antigen.

30. A method as set forth in claim 1 wherein the protein is an antibody.

31. A method as set forth in claim 1 wherein said porous copolymer has a spherical shape.

32. A method as set forth in claim 31 wherein said porous copolymer is a product obtained by suspension polymerization which is carried out in an aqueous solution in the presence of a radical initiator.

33. A composite produced by the method of claim 1 which comprises the porous copolymer and the protein in an amount sufficient to exert activity of said protein adsorbed thereon.

34. A composite as set forth in claim 33 wherein the amount of said protein is at least 10 mg per gram of the copolymer in a dry state.

35. A composite as set forth in claim 34 wherein the amount of said protein is at least 20 mg per gram of the copolymer in a dry state.

36. A composite as set forth in claim 33 wherein the protein is an enzyme.

Details for Patent 4,246,351

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Grifols Therapeutics Llc ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5 albumin (human) For Injection 101138 10/21/1942 ⤷  Try a Trial 1998-01-20
Baxalta Us Inc. BUMINATE, FLEXBUMIN albumin (human) Injection 101452 03/03/1954 ⤷  Try a Trial 1998-01-20
Csl Behring Ag ALBURX albumin (human) Injection 102366 07/23/1976 ⤷  Try a Trial 1998-01-20
Grifols Biologicals Llc ALBUTEIN albumin (human) Injection 102478 08/15/1978 ⤷  Try a Trial 1998-01-20
Instituto Grifols, S.a. HUMAN ALBUMIN GRIFOLS albumin (human) Injection 103352 02/17/1995 ⤷  Try a Trial 1998-01-20
Instituto Grifols, S.a. HUMAN ALBUMIN GRIFOLS albumin (human) Injection 103352 06/11/2003 ⤷  Try a Trial 1998-01-20
Csl Behring Llc ALBUMINAR, ALBUMINAR-20, ALBUMINAR-25, ALBUMINAR-5 albumin (human) Injection 103955 03/17/2000 ⤷  Try a Trial 1998-01-20
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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