Adsorbing pathogen-inactivating compounds with porous particles immobilized in a matrix

• US 20060093999A1
• Filed: 10/04/2005
• Published: 05/04/2006
• Est. Priority Date: 01/06/1998
• Status: Active Grant

• Current Assignee: Cerus Corporation
• Original Assignee: Cerus Corporation
• Inventors: Hei, Derek J.
• Granted Patent: US 7,611,831 B2
• Time in Patent Office: Days
• US Class Current: 435/2
• CPC Class Codes: A01N 1/0215 Disinfecting agents, e.g. antimicrobials for preserving living parts
• CPC Class Codes: A01N 1/0231 Chemically defined matrices, e.g. alginate gels, for immobilising, holding or storing cells, tissue or organs for preservation purposes; Chemically altering or fixing cells, tissue or organs, e.g. by cross-linking, for preservation purposes
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• CPC Class Codes: A61L 2/00 Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for contact lenses A61L12/00; atomisers for disinfecting agents A61M; sterilisation of packages or package contents in association with packaging B65B55/00; treatment of water, waste water, sewage or sludge C02F; disinfecting paper D21H21/36; disinfecting devices for water closets E03D; articles having provision for disinfection, see the relevant subclasses for these articles, e.g. H04R1/12
• CPC Class Codes: A61L 2/0082 using chemical substances
• CPC Class Codes: A61L 2202/22 Blood or products thereof
• CPC Class Codes: A61M 1/0209 Multiple bag systems for separating or storing blood components
• CPC Class Codes: A61M 1/0218 with filters
• CPC Class Codes: A61M 1/3616 Batch-type treatment
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 1/3686 by removing photoactive agents after irradiation
• CPC Class Codes: B01J 20/20 comprising free carbon; comprising carbon obtained by carbonising processes
• CPC Class Codes: B01J 20/26 Synthetic macromolecular compounds
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/28004 Sorbent size or size distribution, e.g. particle size
• CPC Class Codes: B01J 20/28014 characterised by their form
• CPC Class Codes: B01J 20/28019 Spherical, ellipsoidal or cylindrical
• CPC Class Codes: B01J 20/28026 Particles within, immobilised, dispersed, entrapped in or on a matrix, e.g. a resin
• CPC Class Codes: B01J 20/28028 Particles immobilised within fibres or filaments
• CPC Class Codes: B01J 20/28057 Surface area, e.g. B.E.T specific surface area
• CPC Class Codes: B01J 20/28064 : being in the range 500-1000 m2/g
• CPC Class Codes: B01J 20/28066 : being more than 1000 m2/g
• CPC Class Codes: B01J 20/28078 : Pore diameter
• CPC Class Codes: B01J 20/28083 : being in the range 2-50 nm, i.e. mesopores
• CPC Class Codes: B01J 20/28085 : being more than 50 nm, i.e. macropores
• CPC Class Codes: C07D 219/10 : attached in position 9
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 493/04 : Ortho-condensed systems
• CPC Class Codes: C07F 9/64 : Acridine or hydrogenated acridine ring systems

Abstract

Methods and devices are provided for reducing the concentration of low molecular weight compounds in a biological composition containing cells while substantially maintaining a desired biological activity of the biological composition. The device comprises highly porous adsorbent particles, and the adsorbent particles are immobilized by an inert matrix. The matrix containing the particles is contained in a housing, and the particles range in diameter from about 100 μm to about 1500 μm. The device can be used to adsorb and remove a pathogen-inactivating compounds from a biological composition such as a blood product.

Claims

1. A pathogen-inactivating compound adsorption system for reducing the concentration of a low molecular weight pathogen-inactivating compound in an aqueous biological composition containing cellular elements, wherein the pathogen-inactivating compound adsorption system comprises a housing compatible with the biological composition containing an adsorption medium comprising porous adsorbent particles immobilized by a matrix, wherein the diameter of the adsorbent particles ranges from about 100 μ

m to about 1500 μ

m, wherein the adsorbent particles have an affinity for said pathogen-inactivating compound, wherein the system is configured to remove said pathogen-inactivating compound from said biological composition in a batch process, and wherein the system is configured so that the cellular elements in the biological composition treated with the system maintain sufficient biological activity so that said biological composition is suitable for infusion within a human.

2. A system according to claim 1, wherein the matrix comprises a sintered matrix formed from polymeric particulate material.

3. A system according to claim 1, wherein the matrix comprises a fibrous matrix.

4. A system according to claim 3, wherein the fibrous matrix comprises a synthetic polymer fiber having a polymer core with a high melting temperature surrounded by a sheath with a lower melting temperature.

5. A system according to claim 2 or 3, wherein the porous adsorbent particles have a surface area greater than about 750 m²/g, and the porous adsorbent particles are between 25 and 85 percent of the weight of the adsorption medium.

6. A system according to claim 5, wherein the porous adsorbent particles are between 50 and 80 percent of the weight of the adsorption medium, and the adsorption medium has a particle loading of between 100 and 500 g/m².

7. A system according to claim 6, wherein the adsorption medium has a particle loading of between 250 and 350 g/m².

8. A system according to claim 2, wherein the matrix contains said porous adsorbent particles.

9. A system according to claim 8, wherein the porous adsorbent particles comprise a synthetic polymeric adsorbent having a porous network structure and having a surface area greater than about 750 m²/g.

10. A system according to claim 8, wherein the porous adsorbent particles comprise activated carbon.

11. A system according to claim 9, wherein the porous adsorbent particles comprise a polyaromatic resin.

12. A system according to claim 11, wherein said resin has a pore size between about 25 and 800 Å

.

13. A system according to claim 12, wherein said resin has a pore size between about 25 and 150 Å

.

14. A system according to claim 13, wherein said resin has a pore size between about 25 and 50 Å

.

15. A system according to claim 9, wherein the porous adsorbent particles do not require prewetting before use.

16. A system according to claim 9, wherein the porous adsorbent particles comprise a hypercrosslinked resin.

17. A system according to claim 10, wherein the porous adsorbent particles comprise activated carbon having a surface area between about 1000 and 3000 m²/g.

18. A system according to claim 17, wherein the activated carbon is derived from a synthetic source and at least about 50% of pores of the activated carbon particles have a diameter less than about 20 Å

.

19. A system according to claim 9, wherein the diameter of the porous adsorbent particles is between about 300 and 900 μ

m.

20. A system according to claim 10, wherein the diameter of the porous adsorbent particles is between about 300 and 900 μ

m.

21. A system according to claim 2 wherein the pathogen inactivating compound comprises a nucleic acid-binding compound.

22. A system according to claim 21, wherein the nucleic acid-binding compound comprises a psoralen derivative.

23. A system according to claim 21, wherein the nucleic acid-binding compound comprises an acridine derivative.

24. A system according to claim 21, wherein the nucleic acid-binding compound comprises a dye.

25. A system according to claim 21, wherein the nucleic acid-binding compound has an electrophilic group or a group capable of forming an electrophilic group.

26. A system according to claim 25, wherein the porous adsorbent particles additionally have an affinity for a quencher.

27. A system according to claim 21, wherein the porous adsorbent particles additionally have an affinity for a degradation product of said nucleic acid-binding compound.

28. A method for reducing the concentration of a low molecular weight compound in a biological composition containing cellular elements, wherein said low molecular weight compound comprises a nucleic acid-binding compound and wherein said method comprises treating the biological composition with a system of claim 21 for between about 0.5 hour and 5 weeks to adsorb the low molecular weight compound onto the porous adsorbent particles of the system and reduce the concentration of the low molecular weight compound in the biological composition, wherein the cellular elements in the biological composition treated with the system maintain sufficient biological activity so that said biological composition is suitable for infusion within a human.

29. A method for reducing the concentration of a low molecular weight compound in a biological composition containing cellular elements, wherein said low molecular weight compound comprises a psoralen nucleic acid-binding compound and wherein said method comprises treating the biological composition with a system of claim 21 for between about 0.5 hour and 5 weeks to adsorb the low molecular weight compound onto the porous adsorbent particles of the system and reduce the concentration of the low molecular weight compound in the biological composition, wherein the cellular elements in the biological composition treated with the system maintain sufficient biological activity so that said biological composition is suitable for infusion within a human.

30. A method according to claim 29, wherein no more than about ten percent of an amount of said psoralen nucleic acid-binding compound originally added to said biological composition remains as free psoralen in said biological composition.

31. A method according to claim 29, wherein said psoralen nucleic acid-binding compound is selected from the group consisting of 4′

-(4-amino-2-oxa)butyl-4,5′

,8-trimethyl psoralen, 8-methoxypsoralen, halogenated psoralens, isopsoralens and psoralens linked to quaternary amines, 5′

-bromomethyl-4,4′

,8-trimethylpsoralen, 4′

-bromomethyl-4,5′

,8-trimethylpsoralen, 4′

-(4-amino-2-aza)butyl-4,5′

,8-trimethylpsoralen, 4′

-(2-aminoethyl)-4,5′

,8-trimethylpsoralen, 4′

-(5-amino-2-oxa)pentyl-4,5′

,8-trimethylpsoralen, 4′

-(5-amino-2-aza)pentyl-4,5′

,8-trimethylpsoralen, 4′

-(6-amino-2-aza)hexyl-4,5′

,8-trimethylpsoralen, 4′

-(7-amino-2,5-oxa)heptyl-4,5′

,8-trimethylpsoralen, 4′

-(12-amino-8-aza-2,5-dioxa)dodecyl-4,5′

,8-trimethylpsoralen, 4′

-(13-amino-2-aza-6, 1 1-dioxa)tridecyl-4,5′

,8-trimethylpsoralen, 4′

-(7-amino-2-aza)heptyl-4,5′

,8-trimethylpsoralen, 4′

-(7-amino-2-aza-5-oxa)heptyl-4,5′

,8-trimethylpsoralen, 4′

-(9-amino-2,6-diaza)nonyl-4,5′

,8-trimethylpsoralen, 4′

-(8-amino-5-aza-2-oxa)octyl-4,5′

,8-trimethylpsoralen, 4′

-(9-amino-5-aza-2-oxa)nonyl-4,5′

,8-trimethylpsoralen, 4′

-(14-amino-2,6,11-triaza)tetradecyl-4,5′

,8-trimethylpsoralen, 5′

-(4-amino-2-aza)butyl-4,4′

,8-trimethylpsoralen, 5′

-(6-amino-2-aza)hexyl-4,4′

,8-trimethylpsoralen and 5′

-(4-amino-2-oxa)butyl-4,4′

,8-trimethylpsoralen.

32. A method according to claim 28, wherein the nucleic acid-binding compound adsorbed onto the porous adsorbent particles of the system comprises an acridine derivative.

33. A method according to claim 28, wherein the nucleic acid-binding compound adsorbed onto the porous adsorbent particles of the system comprises a dye.

34. A method according to claim 28, wherein the biological composition contacts the porous adsorbent particles and the matrix at a temperature of about 22°

C. for between about 0.5 hour and seven days.

35. A method according to claim 34, wherein the biological composition comprises platelets.

36. A method according to claim 34, wherein the biological composition contacts the porous adsorbent particles and the matrix at a temperature of about 22°

C. for between about 0.5 and about 36 hours.

37. A method according to claim 36, wherein the biological composition is treated with the system at a temperature of about 22°

C. for between about 0.5 and about 24 hours.

38. A method according to claim 36, wherein the biological composition is treated with the system at a temperature of about 22°

C. for between about 0.5 and about 12 hours

39. A method according to claim 37 and further comprising subsequently contacting the biological composition with the adsorbent particles and the matrix at a temperature of about 4°

C.

40. A method according to claim 39, wherein said biological composition contacts the adsorbent particles for at a temperature of about 4°

C. for up to 5 weeks.

41. A method according to claim 39, wherein said biological composition comprises red blood cells.

42. A method according to claim 28, wherein the biological composition comprises a blood product.

43. A method according to claim 29, wherein the biological composition comprises a blood product.

44. A method according to claim 30, wherein the biological composition comprises a blood product.

45. A method according to claim 31, wherein the biological composition comprises a blood product.

46. A method according to claim 32, wherein the biological composition comprises a blood product.

47. A method according to claim 33, wherein the biological composition comprises a blood product.

48. A method according to claim 34, wherein the biological composition comprises a blood product.

49. A method according to claim 36, wherein the biological composition comprises a blood product.

50. A method according to claim 37, wherein the biological composition comprises a blood product

51. A method according to claim 38, wherein the biological composition comprises a blood product.

52. A method according to claim 39, wherein the biological composition comprises a blood product.

53. A method according to claim 40, wherein the biological composition comprises a blood product.

54. A method according to claim 32, wherein the acridine derivative comprises 5-[(β

-carboxyethyl)amino]acridine.

55. A blood product formed by a method according to claim 28.

56. A blood product formed by a method according to claim 29.

57. A blood product formed by a method according to claim 31.

58. A blood product formed by a method according to claim 32.

59. A blood product formed by a method according to claim 41.

60. A blood product formed by a method according to claim 54.

61. A blood product formed by a method according to claim 28 wherein said biological composition comprises red blood cells.

62. A blood product formed by a method according to claim 28 wherein said biological composition comprises platelets.

63. A system according to claim 1, 2, or 16, wherein the adsorbent particles have an internal surface area between about 300 and 1100 m²/g.

64. A system according to claim 1, 2, or 8 wherein the pores adsorbent particles comprise macroreticular adsorbent particles possessing both macropores and micropores.

65. A method according to claim 28 or claim 29 wherein the biological composition containing said cellular elements after contacting the porous adsorbent particles has improved yield of cells over a comparable method in which said porous adsorbent particles are not immobilized.

66. A method according to claim 28 or claim 29 wherein the biological composition containing said cellular elements after contacting the porous adsorbent particles has improved performance in an in vitro assay over a comparable method in which said porous adsorbent particles are not immobilized.

67. A biological composition formed by a method according to claim 65.

68. A biological composition formed by a method according to claim 66.