ABSORBING PATHOGEN-INACTIVATING COMPOUNDS WITH POROUS PARTICLES IMMOBILIZED IN A MATRIX

• US 20050142542A1
• Filed: 12/10/2001
• Published: 06/30/2005
• Est. Priority Date: 01/06/1997
• Status: Active Grant

• Current Assignee: Cerus Corporation
• Original Assignee: Cerus Corporation
• Inventors: Clarke, Michael S., Hei, Derek J.
• Granted Patent: US 6,951,713 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A01N 1/0205 Chemical aspects
• CPC Class Codes: A01N 1/0236 Mechanical aspects
• CPC Class Codes: A01N 1/0242 Apparatuses, i.e. devices used in the process of preservation of living parts, such as pumps, refrigeration devices or any other devices featuring moving parts and/or temperature controlling components
• CPC Class Codes: A01N 1/0278 Physical preservation processes
• 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: A61M 1/0209 Multiple bag systems for separating or storing blood components
• CPC Class Codes: A61M 1/0218 with filters
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: B01D 15/00 Separating processes involving the treatment of liquids with solid sorbents using liquid sorbents B01D11/00; ion exchange processes or materials, sorbent materials in general B01J, e.g. sorbents for chromatography B01J20/281; for investigating or analysing materials G01N30/00; Apparatus therefor
• CPC Class Codes: B01J 20/20 comprising free carbon; comprising carbon obtained by carbonising processes
• CPC Class Codes: B01J 20/28004 Sorbent size or size distribution, e.g. particle size
• 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 20/28078 Pore diameter
• 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, 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 1 μm to about 200 μm. The matrix can be fibrous, and the particles can have a surface area greater than 750 m²/g and a pore diameter between about 25 and 800 Å. The device can be used to adsorb and remove a pathogen-inactivating compound that is a nucleic acid-binding compound such as psoralen, an acridine derivative or a dye from a biological composition such as a blood product.

Claims

1-57. -57. (canceled)

58. A pathogen-inactivating compound adsorption system for reducing the concentration of a low molecular weight pathogen-inactivating compound in a biological composition, wherein the pathogen-inactivating compound adsorption system comprises a housing compatible with the biological composition and containing an adsorption medium comprising adsorbent particles having a network pore structure immobilized within a sintered matrix formed from polymeric particulate material, wherein the diameter of the adsorbent particles ranges from about 1 μ

m to about 200 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 flow process, wherein the system is configured so that the biological composition treated with the system maintains sufficient biological activity so that said biological composition is suitable for infusion within a human.

60. A system according to claim 58, wherein the diameter of the adsorbent particles is between about 50 and 150 μ

m.

65. A system according to claim 58, wherein the particle containing matrix is at least 3 mm thick.

66. A system according to claim 58, wherein the adsorbent particles comprise adsorbent resin particles have a surface area greater than about 750 m²/g, and the porous adsorbent particles are between 30 and 70 percent of the weight of the adsorption medium.

68. A system according to claim 58, wherein the adsorbent particles comprise adsorbent resin particles having a surface area greater than about 750 m²/g.

69. A system according to claim 68, wherein the adsorbent resin particles are polyaromatic.

70. A system according to claim 69, wherein said adsorbent resin particles have a pore diameter between about 25 and 800 Å

.

71. A system according to claim 70, wherein said adsorbent resin particles have a pore diameter between about 25 and 150 Å

.

72. A system according to claim 71, wherein said adsorbent resin particles have a pore diameter between about 25 and 50 Å

.

73. A system according to claim 68, wherein the adsorbent resin particles do not require prewetting before use.

74. A system according to claim 68, wherein the adsorbent resin particles are hypercrosslinked.

75. A system according to claim 58 or claim 68 wherein the pathogen inactivating compound comprises a nucleic acid-binding compound.

76. A system according to claim 75, wherein the nucleic acid-binding compound comprises a psoralen.

77. A system according to claim 75, wherein the nucleic acid-binding compound comprises an acridine derivative.

78. A system according to claim 75, wherein the nucleic acid-binding compound comprises a dye.

79. A system according to claim 75, wherein the adsorbent particles have an affinity for a nucleic acid-binding compound having an electrophilic group capable of reacting with a nucleophilic group of a quencher that quenches undesired side reactions of the pathogen-inactivating compound.

80. A system according to claim 79, wherein the adsorbent particles additionally have an affinity for said quencher.

81. A system according to claim 75, wherein the adsorbent particles additionally have an affinity for a degradation product of said nucleic acid-binding compound.

82. A method for reducing the concentration of a low molecular weight compound comprising a pathogen-inactivating compound in a biological composition, said method comprising treating the biological composition with a system of claim 58 or claim 68 to bind the low molecular weight compound to the adsorbent particles and thereby reduce the concentration of the low molecular weight compound in the biological composition, wherein the biological composition treated with the system maintains sufficient biological activity so that said biological composition is suitable for infusion within a human.

83. A method for reducing the concentration of a low molecular weight compound comprising a nucleic acid-binding compound in a biological composition, said method comprising treating the biological composition with a system of claim 75 to bind the low molecular weight compound to the adsorbent particles and thereby reduce the concentration of the low molecular weight compound in the biological composition, wherein the biological composition treated with the system maintains sufficient biological activity so that said biological composition is suitable for infusion within a human.

84. A method for reducing the concentration of a low molecular weight compound comprising a psoralen nucleic acid-binding compound in a biological composition, said method comprising treating the biological composition with a system of claim 75 to bind the low molecular weight compound to the adsorbent particles and thereby reduce the concentration of the low molecular weight compound in the biological composition, wherein the biological composition treated with the system maintains sufficient biological activity so that said biological composition is suitable for infusion within a human.

85. A method according to claim 84, 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.

86. A method according to claim 84, 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-6,11-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′

-(1 4-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.

87. A method according to claim 83 wherein the nucleic acid-binding compound comprises an acridine derivative.

88. A method according to claim 87, wherein the acridine derivative comprises N-(9-acridinyl)-β

-alanine.

89. A method according to claim 83, wherein the nucleic acid-binding compound comprises a dye.

90. A method according to claim 89, wherein the dye comprises methylene blue.

91. A method according claim 84, wherein the biological composition comprises a blood product.

92. A method according to claim 91, wherein the blood product consists essentially of plasma.

93. A method according to claim 91, wherein the blood composition flows through the system as a result of a pressure differential which arises due to a hydrostatic head.

94. A method according to claim 91, wherein the blood composition flows through the system as a result of a pressure differential which arises due to the use of a pump.

95. A method according to claim 91, wherein the blood composition flows through the system at a flux between about 0.1 mL/cm²/min and about 10 mL/cm²/min.

96. A method according to claim 95, wherein the blood composition flows through the system at a flux between about 0.2 mL/cm²/min and about 5 mL/cm²/min.

97. A method according to claim 91, wherein the blood composition contains an original amount of factor XI, and said blood composition has at least about 91% of said original amount of factor XI after said treating with said system.

104. A system according to claim 58, wherein the adsorbent particles have an internal surface area between about 300 and 1100 m²/g.

105. A system according to claim 58 or claim 68 wherein the sintered matrix comprises a polyolefin.

106. A system according to claim 105 wherein the polyolefin comprises polyethylene.

107. A system according to claim 106 wherein the polyethylene comprises an ultra high molecular weight polyethylene.

108. A system according to claim 58 wherein the adsorbent particles comprise activated carbon.

109. A system according to claim 108 wherein the activated carbon has a surface area greater than 950 m²/g.

110. A system according to claim 109 wherein the activated carbon has a surface area greater than 1200 m²/g.

111. A system according to claim 110 wherein the activated carbon has a surface area of about 2000 m²/g.

112. A system according to claim 108 wherein the activated carbon is formed by steam activation of coconut shells.

113. A system according to claim 68 wherein said adsorbent particles comprise nonionic macroporous and macroreticular resin particles having macropores and micropores.

114. A method according to claim 91 wherein said blood product additionally contains activated complement and said adsorbent particles additionally bind the activated complement in said blood product.

59. (canceled)

61. (canceled)

62. (canceled)

63. (canceled)

64. (canceled)

67. (canceled)

98-103. -103. (canceled)