USE OF A COLLOIDAL SUSPENSION OF A CATIONIC POLYMER TO TREAT A SUPPORT FOR MEDICAL USE

• US 20090206038A1
• Filed: 09/06/2006
• Published: 08/20/2009
• Est. Priority Date: 06/22/2006
• Status: Active Grant

• Current Assignee: Gambro Lundia AB (Baxter International Inc.)
• Original Assignee: Gambro Lundia AB (Baxter International Inc.)
• Inventors: Thomas, Michel
• Granted Patent: US 8,137,562 B2
• Time in Patent Office: Days
• US Class Current: 210/639
• CPC Class Codes: A61L 33/06 Use of macromolecular materials grafting of a monomer onto the substrate A61L33/0088
• CPC Class Codes: B01D 2323/38 Graft polymerization
• CPC Class Codes: B01D 2325/12 Adsorbents being present on the surface of the membranes or in the pores
• CPC Class Codes: B01D 2325/14 Membrane materials having negatively charged functional groups
• CPC Class Codes: B01D 67/0093 Chemical modification
• CPC Class Codes: B01D 67/00933 by addition of a layer chemically bonded to the membrane
• CPC Class Codes: B01D 69/02 characterised by their properties
• CPC Class Codes: B01D 71/82 characterised by the presence of specified groups, e.g. introduced by chemical after-treatment
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

The invention concerns a composite support comprising a base support for the treatment of a biological fluid, in which: “the base support is essentially-constituted by a first polymer carrying anionic or anionizable groups;” at least a part of the surface of the base support is coated with a second polymer ionically bonded to the first polymer, the second polymer carrying the cationic or cationizable groups which are capable of forming an ionic bond with the anionic or anionizable groups of the first polymer; in which the second polymer is in the colloidal form and in mixture with a polyacid during application to the support, allowing the composite membrane to adsorb at least one entity containing anionic or anionizable groups by bonding with cationic or cationizable groups of the second polymer.

Claims

1-55. -55. (canceled)

56. Use of a suspension to treat a base support for medical use essentially constituted by a first polymer containing anionic or anionizable groups, the suspension being in an acidic medium and comprising a second polymer containing cationic or cationizable groups which are capable of forming an ionic bond with the anionic or anionizable groups of the first polymer, the second polymer being in the colloidal form.

57. Use according to claim 56, in which the suspension comprises at least one organic polyacid in association with the second polymer, allowing the second polymer to have said colloidal form.

58. Use according to claim 56, in which the organic polyacid is a polycarboxylic acid.

59. Use according to claim 56, in which the polycarboxylic acid comprises at least three carboxylic acid groups, preferably a tribasic organic acid.

60. Use according to claim 56, in which the polycarboxylic acid is citric acid.

61. Use according to claim 56, in which the second polymer is a cationic polymer selected from polyamines, preferably cationic polyaminoacids, and/or from polyimines, more preferably from the group comprising:

polylysine, polyarginine, polyethyleneimine, copolymers thereof and mixtures thereof.

62. Use according to claim 56, in which the anionic or anionizable groups of the first polymer are selected from sulphonic, phosphonic, carboxylic, sulphuric and phosphoric groups and from salts of said groups.

63. Use according to claim 56, in which the anionic or anionizable groups of the first polymer are acidic sulphonic groups or sulphonic groups in their salt forms.

64. Use according to claim 56, in which the first polymer comprises a polyacrylonitrile, preferably a copolymer of acrylonitrile and sodium methallylsulphonate.

65. Use according to claim 56, of a suspension for the surface treatment of a support base for medical use.

66. Use according to claim 56, of a suspension for the bulk treatment of a base support for medical use.

67. Use according to claim 56, in which the support base used is in the form of a semi permeable membrane, beads, a gel or a foam.

68. A composite support comprising a base support for the treatment of a biological fluid, in which:

the base support is essentially constituted by a first polymer carrying anionic or anionizable groups;

at least a part of the surface of the base support is coated with a second polymer ionically bonded to the first polymer, the second polymer carrying cationic or cationizable groups which are capable of forming an ionic bond with the anionic or anionizable groups of the first polymer;

characterized in that

the second polymer is in the colloidal form, allowing the composite membrane to adsorb at least one entity containing anionic or anionizable groups by bonding with cationic or cationizable groups of the second polymer.

69. A composite support according to claim 68, in which the second polymer is in association with an organic polyacid.

70. A support according to claim 68, in which the anionic or anionizable groups of the first polymer are selected from sulphonic, phosphonic, carboxylic, sulphuric and phosphoric groups and from salts of said groups, and wherein the second polymer is a cationic polymer selected from polyamines, preferably cationic polyaminoacids, and/or from polyimines, more preferably from the group comprising:

polylysine, polyarginine, polyethyleneimine, copolymers thereof and mixtures thereof.

71. A composite support according to claim 68, in which said part of the surface of the support is at least a partially coated with at least one anticoagulation agent carrying anionic or anionizable groups which are capable of forming an ionic bond with the cationic or cationizable groups of the second polymer.

72. A support according to claim 71, in which the anticoagulation agent comprises at least one compound from the glycoaminoglycane family having an anticoagulation activity, said anticoagulation agent preferably being selected from the group comprising:

non fractionated heparin, fractionated heparin, danaparoids, all heparin derivatives, and mixtures of said products.

73. A support according to claim 71, in which the deposited surface concentration of the anticoagulation agent is in the range 1000 to 30000 IU/m² of membrane, preferably in the range 2000 to 8000 IU/m² of membrane.

74. A composite support according to claim 68, in which the surface concentration of the second polymer in the colloidal form is in the range 15 to 200 mg/m².

75. A support according to claim 74, in which the surface concentration of the second polymer in the colloidal form is in the range 15 to 100 mg/m².

76. A support according to claim 68, in which the second polymer comprises chains with a size sufficient not to traverse the base support.

77. A support according to claim 68, in which the second polymer is prepared by ultrafiltration of a solution of second polymer through a semi-permeable membrane to eliminate chains of the second polymer having a size below the size corresponding to the porosity of the base support.

78. A composite support according to claim 68, in which the base support is a semi-permeable base membrane.

79. A support according to claim 78, in which the molecular mass of the second polymer is greater than the cutoff threshold of the semi-permeable membrane produced from the first polymer.

80. A composite support according to claim 68, for use in purification of blood or plasma by extracorporeal circulation, in which the base support is a semi-permeable membrane, the composite membrane comprising at least:

a first part of the surface intended to be brought into contact with the blood or plasma;

a second part of the surface intended to be brought into contact with the dialysate or the filtrate;

in which the first part of the surface of the membrane is covered by the second polymer in the colloidal form and optionally by an anticoagulation agent carrying anionic or anionizable groups which are capable of forming an ionic bond with the cationic or cationizable groups of the second polymer.

81. A support according to claim 80, in which:

the first part of the surface of the membrane is covered by the second polymer in the colloidal form and the anticoagulation agent carrying anionic or anionizable groups, which can form an ionic bond with the cationic or cationizable groups of the second polymer;

the second part of the surface of the membrane is covered by the second polymer in the colloidal form.

82. A support according to claim 80, in which at least the second part of the surface of the membrane is covered by the second polymer in the colloidal form and optionally by an anticoagulation agent carrying anionic or anionizable groups, which can form an ionic bond with the cationic or cationizable groups of the second polymer.

83. A support according to claim 78, in which the semi-permeable membrane is a stack in the form of planar membranes.

84. A support according to claim 80, in which the semi-permeable composite membrane is constituted by a bundle of hollow fibres, and in which the interior surface of the hollow fibres is the first part of the surface intended to be brought into contact with the blood or the plasma and in which the exterior surface of the hollow fibres is the second part of the surface intended to be brought into contact with the filtrate or the dialysate.

85. A support according to claim 68, in which the base support is constituted by one of the following forms:

an assembly of beads, a foam or a gel.

86. A support according to claim 85, in which the base support has a variable porosity.

87. A support according to claim 68, in which the second polymer in the colloidal form is present in the bulk of the support.

88. A composite support according to claim 68, characterized by an endotoxin adsorption capacity in aqueous medium of 500 UE/m² or more for a membrane, preferably 1500 UE/m² or more.

89. A support according to claim 88, in which the adsorption capacity of the endotoxins is in the range 2000 to 5000 UE/m².

101. An exchanger comprising:

a housing defining a first compartment and a second compartment;

the first compartment being provided with an inlet and an outlet and intended for the circulation of biological liquid to be treated;

the second compartment being intended for the circulation of dialysate or filtrate and being provided with an outlet and optionally with an inlet;

the two compartments being separated by a composite support according to claim 68.

105. A device for adsorption of entities contained in a biological fluid, comprising:

a housing provided with an inlet and an outlet and intended for the circulation of biological liquid to be treated;

a composite support according to claim 68 contained in the housing.

106. A method for manufacturing a medical device for the adsorption of entities contained in a biological fluid for the treatment of a biological liquid, the device comprising a housing provided with an inlet and an outlet and being intended for the circulation of biological liquid to be treated, a composite support according to claim 68, the method comprising the following steps:

a1) providing a base support essentially constituted from a first polymer carrying anionic or anionizable groups;

a2) assembling the various components of the device, in particular mounting the base support in the housing;

b1) providing a suspension in an acidic medium containing a second polymer carrying cationic or cationizable groups which can form an ionic bond with the anionic or anionizable groups of the first polymer, the second polymer being in the colloidal form;

b2) bringing the suspension into contact with at least a first portion of the base support intended to be brought into contact with the liquid to be treated;

b3) in the case in which steps (b1-b2) are carried out after step a2), rinsing and/or purging the adsorption device of the solution containing the second polymer;

c1) optionally, sterilizing the exchanger thus obtained.

107. Use of a support according to claim 68, to treat septic syndrome in particular by adsorption of endotoxins contained in a biological fluid.

108. Use of a support according to claim 68, to purify certain molecules contained in blood or plasma by extracorporeal circulation.

109. Use of a support according to claim 68, to reduce systemic anticoagulation in a patient during extracorporeal blood or plasma treatment.

90. A method for manufacturing a composite support for the treatment of biological fluid, said method comprising the following steps:

a) providing a base support essentially constituted by a first polymer carrying anionic or anionizable groups;

b) providing a suspension in an acidic medium comprising a second polymer carrying cationic or cationizable groups which are capable of forming an ionic bond with the anionic or anionizable groups of the first polymer, the second polymer being in the colloidal form;

c) bringing the suspension into contact with at least a portion of the surface of the base support.

91. A method according to claim 90, in which the anionic or anionizable groups of the first polymer are selected from sulphonic, phosphonic, carboxylic, sulphuric and phosphoric groups and from salts of said groups, and wherein the second polymer is a cationic polymer selected from polyamines, preferably cationic polyaminoacids, and/or from polyimines, more preferably from the group comprising:

polylysine, polyarginine, polyethyleneimine, copolymers thereof and mixtures thereof.

92. A method according to claim 91, in which the second polymer is obtained in the colloidal form by a step for mixing a first solution comprising the second polymer with a second solution comprising at least one organic polyacid.

93. A method according to claim 92, in which the organic polyacid is a polycarboxylic acid.

94. A method according to claim 93, in which the ratio of the concentration of the second polymer in the suspension to the concentration of organic polyacid in the suspension is such that it can produce a suspension in the colloidal form.

95. A method according to claim 94, in which the second polymer is polyethyleneimine and the polyacid is citric acid, said ratio of the concentration of polyethyleneimine and citric acid being in the range 0.9 to 1.1.

96. A method according to claim 90, the method comprising, after step c), as step d) as follows:

bringing at least a portion of said part of the surface of the base support into contact with a solution comprising at least one anticoagulation agent carrying anionic or anionizable groups which can form an ionic bond with the cationic or cationizable groups of the second polymer to bind an anticoagulation coating onto said portion of the part of the surface of the support coated with the second polymer.

97. A method according to claim 96, in which step d) is carried out just before use of a support for the treatment of a composite biological fluid or during the manufacture of the composite support.

98. A method according to claim 90, comprising as the ultimate step, manufacturing a step for sterilization of the support, such as sterilization with gamma irradiation or sterilization with ethylene oxide which may or may not be preceded by gamma irradiation.

99. A method according to claim 90, in which the first solution comprising the second polymer is prepared by ultrafiltration of a solution of second polymer through a semi-permeable membrane to eliminate chains of the second polymer having a size which is less than or equal to the size corresponding to the porosity of the base support.

100. A method according to claim 90, in which the treatment with the suspension in an acid medium of the second polymer in the colloidal form is carried out in at least a portion of the bulk of the base support.

102. A method for manufacturing an exchanger for the treatment of a biological liquid, the exchanger comprising a housing defining a first compartment and a second compartment, the first compartment being provided with an inlet and an outlet and being intended for the circulation of biological liquid to be treated, the second compartment being intended for the circulation of dialysate or filtrate and being provided with an outlet and optionally with an inlet, the two compartments being separated by a base support, the method comprising the following steps:

a1) providing a base support essentially constituted from a first polymer carrying anionic or anionizable groups;

a2) assembling the various components of the exchanger, in particular mounting the base support in the housing;

b1) providing a suspension in an acidic medium containing a second polymer carrying cationic or cationizable groups which can form an ionic bond with the anionic or anionizable groups of the first polymer, the second polymer being in the colloidal form;

b2) bringing the suspension into contact with at least a first portion of the surface of the base support intended to be brought into contact with the liquid to be treated;

b3) in the case in which steps (b1-b2) are carried out after step a2), rinsing and/or purging the exchanger of the solution containing the second polymer;

c1) optionally, sterilizing the exchanger thus obtained.

103. A method according to claim 102 comprising, after steps b), a step c0) for bringing at least one solution of an anticoagulation agent into contact in a liquid medium with at least a portion of the part of the surface of the base support coated with the second polymer in the colloidal form to bind an anticoagulating coating onto the surface of the support coated with second polymer in the colloidal form;

step c0) may be carried out before or after step a2).

104. A method according to claim 102, in which the anionic or anionizable groups of the first polymer are selected from sulphonic, phosphonic, carboxylic, sulphuric and phosphoric groups and from salts of said groups, and wherein the second polymer is a cationic polymer selected from polyamines, preferably cationic polyaminoacids, and/or from polyimines, more preferably from the group comprising:

polylysine, polyarginine, polyethyleneimine, copolymers thereof and mixtures thereof.