Porous spun polymeric structures and method of making same

• US 20040124146A1
• Filed: 12/30/2002
• Published: 07/01/2004
• Est. Priority Date: 12/30/2002
• Status: Active Grant

• Current Assignee: Boston Scientific Scimed (Boston Scientific Corporation)
• Original Assignee: Scimed Life Systems Incorporated (Boston Scientific Corporation)
• Inventors: Dao, Kinh-Luan D., Chin, Yem, Zhong, Sheng-Ping, Mohan, Kshitij, Vu, Liem
• Granted Patent: US 7,083,697 B2
• Time in Patent Office: Days
• US Class Current: 210/645
• CPC Class Codes: A61M 1/3633 Blood component filters, e.g. leukocyte filters
• CPC Class Codes: B01D 39/163 sintered or bonded
• CPC Class Codes: B01D 61/14 Ultrafiltration; Microfiltration
• CPC Class Codes: B01D 71/06 Organic material
• CPC Class Codes: D04H 3/05 in another pattern, e.g. zig-zag, sinusoidal D04H3/04 takes precedence
• CPC Class Codes: Y10T 156/1798 with liquid adhesive or adhesive activator applying means
• CPC Class Codes: Y10T 428/24 Structurally defined web or sheet [e.g., overall dimension, etc.]
• CPC Class Codes: Y10T 428/24479 including variation in thickness

Abstract

A non-woven polymeric matrix for separating leukocytes from a blood sample includes a non-woven three dimensional matrix formed from polymeric fibers having a predetermined pore volume fraction including a defined channel configuration, a predetermined pore size in the range of from about 10 μm to about 250 μm, and a plurality of connections between the plurality of fibers. The matrix is configured so as to remove at least about 98% of leukocytes from at least one unit of packed red blood cells. Methods of making and using the matrix are also provided.

Claims

1. An apparatus for making a three dimensional non-woven matrix made from a polymer, comprising:

a moveable table capable of motion in a first plane (x) and a second plane (y) perpendicular to said first plane;

control means for controlling the movement of at least said table; and

an applicator configured so as to apply at least one liquid polymeric fiber to said table.

2. The apparatus according to claim 1, wherein said moveable table is capable of motion in a third plane (z) which is perpendicular to said first and second planes.

3. The apparatus according to claim 2, wherein said control means is a computer pre-programmed using computer software.

4. A method of making a three dimensional non-woven porous polymeric matrix, comprising the steps of:

providing at least one liquid polymer capable of forming a fiber;

feeding said polymer through at least one applicator to form at least one polymeric fiber;

applying said polymeric fiber in a plurality of layers onto a moveable table capable of motion in at least a first plane (x) and a second plane (y); and

controlling at least a motion of said table so as to form a three dimensional non-woven porous polymeric matrix comprised of interconnected fibers.

5. The method according to claim 4, wherein said matrix has a predetermined shape, a predetermined pore volume fraction including a defined channel configuration, a predetermined pore size, and a plurality of connections between said plurality of fibers.

6. The method according to claim 4, wherein said fiber is formed by melting a solid polymer followed by cooling.

7. The method according to claim 4, wherein said liquid polymer is formed by admixing a polymer and a solvent.

8. The method according to claim 7, wherein said plurality of connections are formed from cross adherence of fiber contact points after removal of solvent by evaporation, applied vacuum, applied heat or a combination thereof.

9. The method according to claim 4, wherein said fiber is formed from one of a biodegradable polymer and a combination of a non-biodegradable and a biostable polymer.

10. The method according to claim 4, wherein said polymer is selected from the group consisting of an alginate, a hyaluronic acid, a cellulose, a dextran, a pullane, a polyhyaluronic acid, a chitin, a poly(3-hydroxyalkanoate), a poly(3-hydroxyoctanoate), a poly(3-hydroxyfatty acid), a collagen, a zein, a casein, a gelatin, a gluten, a serum albumen, a polyphosphazene, poly(vinyl alcohol), a polyamide, a polyester amide, a poly(amino acid), a polyanhydride, a polyester, a polycarbonate, a polyacrylate, a polyalkylene, a polyacrylamide, a polyalkylene glycol, a polyalkylene oxide, a polyalkylene terephthalate, a polyortho ester, a polyvinyl ether, a polyvinyl ester, a polyvinyl halide, a polyvinyl pyrrolidone, a polylactide, a polyglyxolide, a polysiloxane, a polycaprolactone, a polyhydroxybutrate, a polyurethane, a poly α

-hydroxy acid, a poly L-lactic acid, a polyglycolic acid, a styrene isobutylstyrene block polymer and blends and copolymers thereof.

11. The method according to claim 4, further comprising the step of programming a computer to direct said table in relation to said applicator.

12. The method according to claim 4, wherein said controlling further comprises controlling a motion of said applicator.

13. The method according to claim 5, wherein said predetermined shape is selected from the group consisting of a sheet, a tube, a cylinder, a sphere, a semi-circle, a cube, a rectangle, a wedge, and an irregular shape.

14. The method according to claim 5, wherein said predetermined pore size is from about 0.5 micron to about 500 microns.

15. The method according to claim 5, wherein said predetermined pore volume fraction is from about 15% to about 98%.

35. A non-woven matrix material for use in a medical device comprising a non-woven three dimensional matrix of polymeric fibers formed according to the method of claim 5.

37. The matrix material according to claim 35, wherein said predetermined pore volume fraction is from about 15% to about 98%.

38. The matrix material according to claim 35, wherein said defined channel configuration includes a series of substantially parallel pores.

39. The matrix according to claim 35, wherein said polymeric fibers are formed from a biocompatible thermoplastic polymer.

40. The matrix according to claim 35, wherein said polymer is selected from the group consisting of an alginate, a hyaluronic acid, a cellulose, a dextran, a polyhyaluronic acid, a chitin, a poly(3-hydroxyalkanoate), a poly(3-hydroxyoctanoate), a poly(3-hydroxyfatty acid), a collagen, a zein, a casein, a gluten, a polyphosphazene, poly(vinyl alcohol), a polyamide, a polyester amide, a poly(amino acid), a polyanhydride, a polyester, a polycarbonate, a polyacrylate, a polyalkylene, a polyalkylene glycol, a polyalkylene oxide, a polyalkylene terephthalate, a polyortho ester, a polyvinyl ether, a polyvinyl ester, a polyvinyl halide, a polylactide, a polyglyxolide, a polysiloxane, a polycaprolactone, a polyhydroxybutrate, a polyurethane, a poly α

-hydroxy acid, a poly L-lactic acid, a polyglycolic acid, a styrene isobutyl styrene block polymer and copolymers and blends thereof.

41. The matrix according to claim 35, wherein said matrix has a pore volume fraction of from about 15% to about 90%.

42. The matrix according to claim 35, wherein said matrix has a pore size of from about 5 microns to about 500 microns.

43. The matrix according to claim 35, wherein said matrix has a pore size of from about 50 microns to about 150 microns.

44. The matrix according to claim 35, wherein said pores are arranged substantially continuously throughout a depth of said matrix and are substantially parallel with one another.

45. The matrix according to claim 35, wherein said pores are arranged substantially discontinuously throughout a depth of said matrix and are substantially parallel with one another.

46. The matrix according to claim 35, wherein said polymeric fibers possess an average diameter of from about 1 microns to about 40 microns.

47. The matrix according to claim 35, wherein said polymeric fibers possess an average diameter of from about 5 microns to about 15 microns.

48. The matrix according to claim 35, wherein said matrix is at least partially degradable having a predetermined rate of degradation.

54. The matrix according to claim 47, wherein each of said pores runs substantially continuously from a first upstream side of said matrix to a second downstream side of said matrix.

55. The matrix according to claim 47, wherein each of said pores runs substantially discontinuously from a first upstream side of said matrix to a second downstream side of said matrix.

16. A method of making a three dimensional non-woven matrix, comprising the steps of:

admixing at least one fiber forming polymer with a compatible solvent to form a flowable polymer mixture;

applying at least one fiber formed from said polymer mixture to a moveable table capable of motion in a first plane (x), a second plane (y) perpendicular to said first plane, and a third plane (z) perpendicular to said first plane (x) and said second plane (y); and

controlling movement of at least said table so as to form a three dimensional non-woven matrix of fibers having a predetermined pore volume fraction including a defined channel configuration, a predetermined pore size, and a plurality of connections between said fibers.

17. The method according to claim 16, wherein said fiber is formed by melting a solid polymer followed by cooling.

18. The method according to claim 16, wherein said flowable polymer is formed by admixing a polymer and a solvent.

19. The method according to claim 16, wherein said plurality of connections are formed from cross adherence of fiber contact points after removal of solvent by evaporation, applied vacuum, applied heat or a combination thereof.

20. The method according to claim 16, wherein said fiber is formed from one of a biodegradable polymer and a combination biodegradable and biostable polymer.

21. The method according to claim 16, wherein said admixing step comprises admixing a polyurethane polymer and at least one further polymer.

22. The method according to claim 16, wherein said applying step includes feeding said flowable polymer mixture through at least one spinneret having a plurality of holes.

23. The method according to claim 22, wherein said admixing step includes forming two different flowable polymer mixtures consisting of a first flowable mixture and a second flowable mixture, said applying step includes feeding said first flowable polymer mixture through a first spinneret and feeding said second flowable polymer mixture through a second spinneret.

24. The method according to claim 23, wherein said applying step comprises simultaneously applying said first flowable polymer and said second flowable polymer.

25. The method according to claim 23, wherein said applying step comprises alternating application of said first flowable polymer and said second flowable polymer.

26. The method according to claim 23, wherein said flowable polymer mixture comprises a plurality of flowable polymers, wherein said applying step includes one of sequential and simultaneous application of said plurality of flowable polymers.

27. The method according to claim 26, wherein a portion of said plurality of flowable polymers is applied simultaneously and a remainder of said plurality of flowable polymers is applied sequentially.

28. The method according to claim 16, wherein said applying step includes applying said flowable polymer in a plurality of fibers having an average diameter of from about 1 microns to about 40 microns.

29. The method according to claim 16, wherein said applying step comprises administering an electrostatic charge to said fibers, at least during an initial phase of application of said flowable polymer.

30. The method according to claim 16, wherein said controlling step comprises programming a computer attached to said moveable table to define movement of at least said table.

31. The method according to claim 30, wherein said computer is controlled using computer assisted design (CAD) software.

32. The method according to claim 16, wherein said controlling step forms a three dimensional non-woven matrix into one of a sheet, a tube, a cylinder, a sphere, a semi-circle, a cube, a rectangle, a wedge, and an irregular shape.

33. The method according to claim 16, wherein said controlling step forms a three dimensional non-woven matrix having a pore volume fraction of from about 15% to about 98%.

34. The method according to claim 16, wherein controlling step forms a three dimensional non-woven matrix having a pore size of from about 1 micron to about 40 microns.

36. A non-woven matrix material for use in a medical device comprising a non-woven three dimensional matrix formed according to the method of claim 16.

49. A non-woven polymeric matrix for separating leukocytes from a blood sample, said matrix having a first upstream side and a second downstream side, and comprising:

a non-woven three dimensional matrix formed from polymeric fibers having a diameter of from about 5 μ

m to about 15 μ

m, the matrix having a predetermined pore volume fraction including a defined channel configuration, a predetermined pore size in the range of from about 10 μ

m to about 250 μ

m, a plurality of connections between said plurality of fibers, and being configured so as to remove at least about 98% of leukocytes from at least one unit of packed red blood cells.

50. The matrix according to claim 49, wherein said matrix further comprises a therapeutic agent.

51. The matrix according to claim 50, wherein said therapeutic agent is an anticoagulant.

52. The matrix according to claim 49, wherein said pores are arranged substantially parallel with a flow of blood therethrough.

53. The matrix according to claim 49, wherein said pores are arranged substantially non-parallel with a flow of blood therethrough.

56. A separation unit for separating leukocytes from a blood sample, comprising:

supply means for supplying a blood sample from which leukocytes are to be separated;

a housing in fluid communication with said supply means, said housing including an inlet and an outlet and defining a fluid flow path therebetween;

a matrix material according to claim 49 arranged in said housing for separating said leukocytes from said blood sample, wherein said matrix material has a first upstream side and a second downstream side, said first side being arranged toward said inlet and said second side being arranged toward said outlet; and

collection means in fluid communication with said housing for collecting said blood sample from which leukocytes have been separated.

57. A method of separating leukocytes from a blood sample comprising the step of passing a blood sample containing leukocytes through the separation unit of claim 56.

58. The method according to claim 57, wherein said separation unit contains a pre-filter having a pore size of from about 50 to about 150 microns.

59. The method according to claim 57, further comprising the step of pre-treating said blood sample with an anticoagulant.