Polyionene transformed modified polysaccharide supports

• US 4,791,063 A
• Filed: 07/23/1985
• Issued: 12/13/1988
• Est. Priority Date: 02/14/1983
• Status: Expired due to Fees

• Current Assignee: Specialty Minerals Incorporated (Minerals Technologies Incorporated)
• Original Assignee: Cuno Incorporated
• Inventors: Chen, Haunn-Lin, Hou, Chung-Jen, Hou, Kenneth C.
• Primary Examiner(s): Rosen, Sam
• Application Number:
  US06/758,064
• Time in Patent Office: 1,239 Days
• Field of Search: 524/27, 524/58, 435/178, 435/179, 435/803, 435/243, 435/253, 435/287, 435/254, 525/54.3, 526/238.2
• US Class Current: 435/243
• 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 20/28033 Membrane, sheet, cloth, pad, lamellar or mat
• CPC Class Codes: B01J 20/28052 Several layers of identical or different sorbents stacked in a housing, e.g. in a column
• CPC Class Codes: B01J 20/3212 consisting of a polymer obtained by reactions otherwise than involving only carbon to carbon unsaturated bonds
• CPC Class Codes: B01J 20/3248 the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
• CPC Class Codes: B01J 20/3251 comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
• CPC Class Codes: B01J 20/3255 comprising a cyclic structure containing at least one of the heteroatoms nitrogen, oxygen or sulfur, e.g. heterocyclic or heteroaromatic structures
• CPC Class Codes: B01J 39/22 Cellulose or wood; Derivatives thereof
• CPC Class Codes: B01J 41/16 Cellulose or wood; Derivatives thereof
• CPC Class Codes: B01J 47/127 in the form of filaments or fibres
• CPC Class Codes: C08F 251/00 Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof
• CPC Class Codes: C08G 81/02 at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
• CPC Class Codes: G01N 2030/386 Radial chromatography, i.e. with mobile phase traversing radially the stationary phase
• CPC Class Codes: G01N 30/6091 Cartridges
• CPC Class Codes: Y10S 435/803 Physical recovery methods, e.g. chromatography, grinding

Abstract

Polyionene-transformed modified polymer-polysaccharide separation matrix and use thereof in removing contaminants of microorganism origin from biological liquids are disclosed.

Claims

1. A polyionene-transformed modified polysaccharide separation matrix comprising a modified polysaccharide having a synthetic polymer covalently coupled thereto and a polyionene bonded to said modified polysaccharide.

2. A separation apparatus for effecting separation of microorganism-originated contaminants from a sample flowing therethrough comprising:

at least one solid stationary phase;

a means for radially distributing the sample through the stationary phase;

wherein the stationary phase comprises;

(a) a swellable fibrous matrix in sheet form spirally wound around the longitudinal axis of the solid phase to form a plurality of layers around the axis;

(b) a spacer means between each layer for permitting controlled swelling thereof and enhancing the distribution of sample flowing radially through the stationary phase, and further wherein the swellable fibrous matrix in sheet form comprises a polyionene-transformed separation matrix of claim 1.

3. A separation apparatus for effecting separation of micro-organism originated contaminants from a sample folowing therethrough comprising:

a housing;

at least one solid stationary phase in said housing, comprising at least one layer of swellable fibrous matrix;

means for distributing said sample through the stationary phase and

means for collecting said sample after the sample has flowed through the stationary phase;

wherein the swellable fibrous matrix in sheet form comprises the polyionene-transformed modified separation matrix of claim 1.

4. A separation apparatus for removing microorganism-originated contaminants from a sample flowing therethrough comprising:

a housing;

at least one solid stationary phase in said housing, comprising;

(a) a plurality of layers of sheets of swellable fibrous matrix and

(b) a spacer means between each said fibrous matrix layer for controlling swelling of the matrix and enhancing the distribution of sample flowing through the stationary phase by substantially evenly dispersing the sample across the matrix;

means for distributing the sample through the stationary phase; and

means for collecting the sample after the sample has flowed through the stationary phase, and wherein said swellable fibrous matrix comprises the polyionene-transformed modified separation matrix of claim 1.

5. A separation apparatus for removing contaminants of microorganism origin from a sample flowing therethrough comprising:

(1) a housing, said housing comprising;

(a) an inlet housing member, and

(b) an outlet housing member, said inlet housing member and said outlet housing member defining a radially, outwardly expanding stationary phase chamber; and

(2) a stationary phase within said radially outwardly expanding stationary phase chamber, said stationary phase chamber comprising at least one layer of a swellable fibrous matrix in sheet form, said swellable fibrous matrix in sheet form comprising the polyionene-transformed modified separation matrix of claim 1.

6. A separation apparatus for removing contaminants of microorganismm origin from a sample flowing therethrough comprising:

(1) a housing, said housing comprising;

(a) an inlet housing member, and

(b) an outlet housing member, said inlet housing member and said outlet housing member defining a stationary phase chamber; and

(2) a stationary phase within said stationary phase chamber, said stationary phase comprising;

(a) a plurality of layers of a swellable fibrous matrix in sheet form;

(b) a spacer means between each layer of said swellable fibrous matrix for permitting controlled swelling thereof and enhancing the distribution of sample flowing through said stationary phase,

wherein said swellable fibrous matrix in sheet form comprises the polyionene-transformed modified separation matrix of claim 1.

7. A separation apparatus for removing contaminants of microorganism origin from a sample flowing therethrough comprising:

(1) a housing, said housing comprising;

(a) an inlet housing member, and

(b) an outlet housing member, said inlet housing member and said outlet housing member defining a radially outwardly expanding stationary phase chamber; and

(2) a stationary phase within said radially, outwardly expanding chamber, said stationary phase comprising;

() a plurality of layers of a swellable fibrous matrix in sheet form, and

(b) a spacer means between each layer of said swellable fibrous matrix for permitting controlled swelling thereof and enhancing the distribution of sample flowing through the stationary phase,

wherein said swellable fibrous matrix in sheet form comprises the polyionene-transformed modified separation matrix of claim 1.

8. The separation apparatus of claim 5 wherein

said inlet housing member comprises a sample inlet means and a sample distribution means, said sample inlet means in communication with said sample distribution means, and

said outlet means comprises a sample collection means and a sample outlet means, said sample collection means in communication with said sample outlet means.

9. The separation apparatus of claim 6 wherein

said inlet housing member comprises a sample inlet means and a sample distribution means, said sample inlet means in communication with said sample distribution means, and

said outlet housing means comprises a sample collection means and a sample outlet means, said sample collection means in communication with said sample outlet means.

10. The separation apparatus of claim 6 wherein

said inlet housing member comprises a sample inlet means and a sample distribution means, said sample inlet means in communication with said sample distribution means, and

said outlet housing means comprises a sample collection means and a sample outlet means, said sample collection means in communication with said sample outlet means.

11. The separation apparatus of claim 8 wherein said sample distribution means comprises radial distribution grooves and concentric distribution channels, said grooves and channels being in communication with each other, and said sample collection means comprises radial collection grooves and concentric collection channels, said radial collection grooves and concentric collection channels in communication with each other.

12. The separation apparatus of claim 9 wherein said sample distribution means comprises radial distribution grooves and concentric distribution channels, said grooves and channels being in communication with each other, and said sample collection means comprises radial collection grooves and concentric collection channels, said radial collection grooves and concentric collection channels in communication with each other.

13. The separation apparatus of claim 10 wherein said sample distribution means comprises radial distribution grooves and concentric distribution channels, said grooves and channels intercommunicating, and said sample collection means comprises radial collection grooves and concentric collection channels, said radial collection grooves and concentric collection channels intercommunicating.

14. The separation apparatus of claims 11, 12 or 13 wherein the volume of said concentric distribution channels and/or said concentric collection channels increases from the interior to the periphery of said column.

15. The separation apparatus of claims 11, 12 or 13 wherein the volume of said radial distribution grooves and/or said radial collection grooves increases from the interior to the periphery of said column.

16. The separation apparatus of claims 8, 9 or 10 wherein said spacer means comprises:

(a) a scrim layer for channeling the sample flow through the matrix and substantially evenly dispersing the sample;

or

(b) a mesh layer to provide a spacing between the layers to permit controlled expansion thereof and assist in distributing the sample;

or

(c) (a) in combination with (b).

17. The separation matrix of claims 2, 3, 4, 5, 6 or 7 wherein separation matrix is polyionene-transformed cellulose.

18. The separation matrix of claims 2, 3, 4, 5, 6 or 7 wherein said separation matrix comprises

(1) polysaccharide covalently coupled to a synthetic polymer;

(2) said synthetic polymer made from at least on of

(a) a polymerizable compound which has a chemical group capable of direct or indirect covalent coupling to said polysaccharide; and

(b) one or more polymerizable compounds containing

(i) an ionizable chemical group,

(ii) a chemical group capable of transformation to an ionizable chemical group,

(iii) a chemical group capable of causing the covalent coupling of said compound (2) to an affinity ligand or biologically active molecule, or

(iv) a hydrophobic chemical group;

wherein said polyionene comprises a water soluble polymer having polyquaternary ammonium groups separated by hydrophobic groups, said hydrophobic groups comprising aromatic groups or alkyl groups, containing at least six carbon atoms.

19. The separation apparatus of claims 2, 3, 4, 5, 6 or 7 wherein said polyionene has the following repeating units:

##STR28## wherein R⁷ and R⁸ are C₁ -C₄ alkyl;

L is --(CH₂)_n --P--(CH₂)_m --;

M is --(CH₂)_o --Q--(CH₂)_p --, with P and Q being the same or different and representing at least one of CH₂, CHA, C₆ H₄, C₆ H₃ A, C₆ H₄ --CHA--C₆ H₄, or R⁹ C₆ H₂ A;

wherein A is a reactive group comprising hydrozy, epoxy, amino, halo, aldelyde or carboxy;

wherein R⁹ is C₁ -C₄ alkyl; and

m, n, o, and p represent integers of 1 to 20.

20. The separation apparatus of claims 2, 3, 4, 5, 6 or 7 wherein said separation matrix comprises a modified cellulose, said modified cellulose comprising cellulose covalently coupled to a synthetic polymer, said synthetic polymer comprising a homopolymer of glycidyl methacrylate, said modified cellulose transformed by the bonding of a polyionene thereto, said polyionene having the following repeating units:

##STR29## wherein L is --(CH₂)₆ -- and M contains at least one of --(CH₂)₁₀ -- and --CH₂ --CHOH--CH₂ --.

21. A polyionene-transformed modified polysaccharide separation matrix which comprises:

(1) polysaccharide covalently coupled to a synthetic polymer;

(2) said synthetic polymer made from at least one of

(a) a polymerizable compound which has a chemical group capable of direct or indirect covalent coupling to said polysaccharide; and

(b) one or more polymerizable compounds containing

(i) an ionizable chemical group,

(ii) a chemical group capable of transformation to an ionizable chemical group,

(iii) a chemical group capable of causing the covalent coupling of said synthetic polymer (2) to an affinity ligand or biologically active molecule, or

(iv) a hydrophobic chemical group;

said modified polysaccharide having bonded thereto, a polyionene.

22. The polyionene-transformed modified polysaccharide separation matrix of claim 21 wherein said polyionene comprises a water-soluble polymer having polyquaternary ammonium groups separated by hydrophobic groups, said hydrophobic groups comprising aromatic groups or alkyl groups, said alkyl groups containing at least six carbon atoms.

23. The polyionene-transformed modified polysaccharide seperation matrix of claim 22 wherein said polyionene has the following repeating units:

##STR30## wherein R⁷ and R⁸ are C₁ -C₄ alkyl;

L is --(CH₂)_n --P--(CH₂)_m --;

M is --(CH₂)_o --(CH₂)_p --, with P and Q being the same or different and representing at least one of CH₂, CHA, C₆ H₄, C₆ H₃ A, C₆ H₄ --CHA--C₆ H₄, or R⁹ C₆ H₂ A;

wherein A is a reactive group comprising hydroxy, epoxy, amino, halo, aldelyde or carboxy;

wherein R⁹ is C₁ -C₄ alkyl; and

m, n, o, and p represent integers of 1 to 20.

24. The separation matrix of claim 22 wherein said polymerizable compound (a) has a chemical group capable of reacting with a hydroxy group of said polysaccharide.

25. The separation of matrix of claim 22 wherein said polysaccharide is fibrous.

26. The separation matrix of claim 22 wherein said polysaccharide is cellulose.

27. The separation matrix of claim 24 wherein said chemical group of said polymerizable compound (a) is a hydroxy reactive O-alkylating chemical agent capable of reacting with the hydroxy group of sad polysaccharide.

28. The separation matrix of claim 27 wherein compound (a) carrying said O-alkylating chemical agent is selected from the group consisting of acrylic anhydride, methacrylic anhydride, -iodo C₂ -C₆ alkyl ester of acrylic acid, -iodo C₂ -C₆ alkyl ester of methacrylic acid, allyl chloride, chloromethyl styrene, chloroacetoxy ethyl methacrylate, glycidyl acrylate, glycidyl methacrylate, 4,5 epoxypentyl-acrylate, 4-(2,3-epoxypropyl)-methacrylate, 9,10-epoxyate arylacrylate, allyl glycidyl ether and ethylene glycol-monoglycidyl ether-acrylate.

29. The separation matrix of claim 21 wherein said synthetic polymer is a homopolymer of glycidyl methacrylate.

30. The separation matrix of claim 22 wherein the polymerizable compound (b) has the formula:

##STR31## wherein R₁ is H or CH₃ ;

A is CO, or SO₂ ;

X is OH, OM where M is a metal ion, OR² where R² is a straight or branched chain C₁ -C₁₈ alkyl group, OR³ OH where R³ is a straight or branched chain C₂ -C₆, alkyl or aromatic group, NR⁴ R⁵ or N+R⁴ R⁵ R⁶ where R⁴, R⁵ and R⁶ are the same or different and are hydrogen, R² or R³ OH;

or

AX taken together has the formula;

##STR32## wherein Y is --CO², --CH₂ CO₂, --SO₃, --CH₂ SO₃, PO₄ H, --CH₂ N(CH₂ COO^-)₂, --CH₂ --NR⁴ R⁵, or --CH₂ N⁺ R⁴ R⁵ R⁶, or the corresponding free acid, R² or R³ OH ester, or partial ester groups thereof.

31. The separation matrix of claim 22 wherein said polymerizable compound (b) contains a chemical group capable of causing the covalent coupling of said polymerizable compound (b) to an affinity ligand or a biologically active molecule.

32. The separation matrix of claim 31 wherein said polymerizable compound (b) carries an electrophilic functional group capable of covalent reaction with nucleophilic group of said affinity ligand or biologically active molecule.

33. The separation matrix of claim 32 wherein said electrophilic group has the formula (II):

##STR33## wherein R'"'"' and R" are the same or different C₁ -C₁₈ alkyl or alkanoyl radicals or R'"'"' and R" together form a 5-7 membered heterocyclic ring with the N atom, and R'"'"'" is a direct bond on a C₂ -C₃ alkyl radical.

34. The separation matrix of claim 27 wherein said chemical group capable of causing said covalent coupling carries an epoxy group.

35. The separation matrix of claim 22 wherein the amount of said polymerizable compound (a) in said synthetic polymer is sufficient to cause substantial covalent coupling of the polymer to said polysaccharide, yet insufficient to cause substantial loss of porosity of the modified polysaccharide.

36. The separation matrix of claim 22 wherein said polymer contains more of said polymerizable compound (b) than of said polymerizable compound (a).

37. The separation matrix of claim 36, wherein the ratio of polymerizable compound (b) to said polymerizable compound (a) is about 88-96% by weight of (b) to 4-12% by weight of (a).

38. The separation matrix of claim 23 wherein L is --(CH₂)₆ -- and M is --(CH₂)₁₀ --.

39. The separation matrix of claim 23 wherein L is --(CH₂)₆ -- and M is --(CH₂)₁₀ -- and --CH₂ --CHOH--CH₂ --.

40. A process for preparing the polyionene-transformed modified polysaccharide separation matrix of claim 21 comprising

(1) reacting said polysaccharide with the chemical group of compound (a) in said synthetic polymer under temperature conditions sufficient to cause said covalent bonding;

and

(2) bonding a polyionene to the reaction product of (1).

41. A self-supporting cellulosic fibrous matrix comprising

(1) cellulose covalently coupled to a synthetic polymer;

and

(2) a polyionene reactively bonded to said cellulose.

42. The self-supporting cellulosic fibrous matrix of claim 41 wherein said synthetic polymer comprises at least one of

(a) a polymerizable compound which has a chemical group capable of direct or indirect covalent coupling to said cellulose;

and

(b) one or more polymerizable compounds containing

(i) an ionizable chemical group;

(ii) a chemical group capable of transformation to an ionizable chemical group;

(iii) a chemical group capable of causing the covalent coupling of said synthetic polymer to an affinity ligand or biologically active molecule, or

(iv) a hydrophobic chemical group;

and said polyionene comprises a water soluble polymer having polyquaternary ammonium groups separated by hydrophobic groups, said hydrophobic groups comprising aromatic groups or alkyl groups, said alkyl groups containing at least six carbon atoms.

43. The self-supporting matrix of claim 42 wherein said synthetic polymer is homopolymer of glycidyl methacrylate.

44. The self-supporting matrix of claim 42 wherein said polyionene has the following repeating units ##STR34## wherein R⁷ and R⁸ are C₁ -C₄ alkyl;

L is --(CH₂)_n --P--(CH₂)_m --;

M is --(CH₂)_o --Q--(CH₂)_p --, with P and Q being the same or different and representing at least one of CH₂, CHA, C₆ H₄, C₆ H₃ A, C₆ H₄ --CHA--C₆ H₄, or R⁹ C₆ H₂ A;

wherein A is a reactive group comprising hydroxy, epoxy, amino, halo, aldelyde or carboxy;

wherein R⁹ is C₁ -C₄ alkyl; and

m, n, o, and p represent integers of 1 to 20.

45. The self-supporting matrix of claim 44 wherein L is --(CH₂)₆ -- and M is --(CH₂)₁₀ --.

46. The self-supporting matrix of claim 44 wherein L is --(CH₂)₆ -- and M is --(CH₂)₁₀ -- and --CH_2--CHOH--CH2 --.

47. The matrix of claim 41 which also comprises highly refined cellulose pulp with a Canadian Standard Freeness of between +100 to -600 ml.

48. The matrix of claim 41 which also comprises in addition a particulate substance having chromatographic or molecular separation functionality.

49. The matrix of claim 41 which is in the form of a sheet.

50. A method for removing and inactivating contaminants of a microorganism origin from a biological liquid comprising passing said liquid through a polyionene-transformed modified polysaccharide matrix wherein said modified polysaccharide matrix comprises

(1) polysaccharide covalently coupled to a synthetic polymer;

(2) said synthetic polymer made from at least one of

(a) a polymerizable compound which has a chemical group capable of direct or indirect covalent coupling to said polysaccharide; and

one or more polymerizable compounds containing

(i) an ionizable chemical group,

(ii) a chemical group capable of transformation to an ionizable chemical group,

(iii) a chemical group capable of causing the covalent coupling of said compound (2) to an affinity ligand or biologically active molecule, or

(iv) a hydrophobic chemical group;

said modified polysaccharide having bonded thereto a polyionene, said polyionene comprising a water-soluble polymer having polyquaternary ammonium groups separated by hydrophobic groups, said hydrophobic groups comprising aromatic groups or alkyl groups, said alkyl groups containing at least six carbon atoms.

51. The method of claim 50 wherein said synthetic polymer is homopolymer of glycidyl methacrylate.

52. The method of claim 50 wherein said polyionene has the following repeating units ##STR35## wherein R⁷ and R⁸ are C₁ -C₄ alkyl;

L is --(CH₂)_n --P--(CH₂)_m --;

M is --(CH₂)_o --Q--(CH₂)_p --, with P and Q being the same or different and representing at least one of CH₂, CHA, C₆ H₄, C₆ H₃ A, C₆ H₄ --CHA--C₆ H₄, or R⁹ C₆ H₂ A;

wherein A is a reactive group comprising hydroxy, epoxy, amino, halo, aldelyde or carboxy;

wherein R⁹ is C₁ -C₄ alkyl; and

m, n, o, and p represent integers of 1 to 20.

53. The method of claim 50 wherein said matrix is in the form of a sheet.

54. The method of claim 53 wherein said sheet is in the form of a disc.

55. The method of claim 50 wherein said biological liquid is peripheral blood.