Size-selective hemocompatible polymer system
Inventors
Young, Wei-Tai • Albright, Robert L. • Golobish, Thomas D. • Capponi, Vincent • Chan, Philip
Assignees
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Publication Number
US-9604196-B2
Publication Date
2017-03-28
Expiration Date
Abstract
A size-selective hemocompatible porous polymeric adsorbent system is provided, the polymer system comprises at least one crosslinking agent and at least one dispersing agent, and the polymer has a plurality of pores with diameters in the range from about 17 to about 40,000 Angstroms.
Core Innovation
The invention relates to a hemocompatible size selective polymer system that defines a porous structure with a plurality of pores having diameters in the range of 17 Angstroms to about 2000 Angstroms. The porous structure includes transport pores having diameters from about 250 Angstroms to about 2000 Angstroms and effective pores having diameters greater than 100 Angstroms to about 250 Angstroms, with transport pore volume greater than about 1.8 to about 78% of a capacity pore volume and effective pore volume greater than about 22 to less than about 98.2% of the capacity pore volume.
In documented embodiments, the size-selective hemocompatible porous polymer uses at least one crosslinking agent and at least one dispersant to form a controlled pore network. The pore-size distribution is used to preferentially adsorb midsize proteins in whole blood while excluding larger proteins above about 50,000 Daltons. The system is described in terms of selective sorption of β2-microglobulin and cytokines, with cytochrome-c as a surrogate, while reducing sorption of albumin, hemoglobin, immunoglobulins, fibrinogen, serum proteins, and other blood proteins larger than 50,000 Daltons.
The patent also documents specific examples of size-selective porous polymer adsorbents synthesized and characterized by pore-structure characterization and competitive adsorption. Adsorbents are evaluated for adsorption selectivity and capacity in competitive adsorption against cytochrome-c and serum albumin, including performance over a four-hour perfusion. A structure–performance correlation is provided based on where effective pore volume falls within the pore-size range, with an adsorbent identified as best overall balance of high cytochrome-c selectivity and capacity over the stated perfusion duration.
Claims Coverage
The independent claims are clm-00001, clm-00009, and clm-00017, each centered on a hemocompatible size selective polymer system with defined transport and effective pore diameters and specified fractions of transport pore volume and effective pore volume relative to a capacity pore volume. The claim set also ties hemocompatible polymer formation to specific component categories, including crosslinking agent and dispersant, and later claims specify initiator, inhibitor, and buffer systems in an organic phase dispersed in an aqueous phase.
Porous hemocompatible size selective polymer structure with transport and effective pore distributions
A hemocompatible size selective polymer system comprising at least one polymer defining a porous structure wherein said porous structure consists of a plurality of pores with diameters in the range of 17 Angstroms to about 2000 Angstroms, said at least one polymer comprising transport pores with diameters from about 250 Angstroms to about 2000 Angstroms and effective pores with diameters greater than 100 Angstroms to about 250 Angstroms, and wherein said at least one polymer has a transport pore volume greater than about 1.8 to about 78% of a capacity pore volume and an effective pore volume greater than about 22 to less than about 98.2% of the capacity pore volume.
Hemocompatible size selective porous polymer formed in organic phase dispersed in aqueous phase
A size selective hemocompatible surface coated polymer system comprising at least one polymer formed by polymerizing monomers in an organic phase, wherein said organic phase is dispersed in an aqueous phase, said aqueous phase comprises at least one dispersing agent, at least one free radical inhibitor and at least one buffering agent, and wherein said at least one polymer defines a porous structure with pores with diameters in the range of 17 Angstroms to about 2000 Angstroms, including transport pores and effective pores as defined, with transport pore volume greater than about 1.8 to about 78% of a capacity pore volume and effective pore volume greater than about 22 to less than about 98.2% of the capacity pore volume.
Hemocompatible size selective polymer system produced by polymerizing monomers in organic phase dispersed in aqueous phase with transport and effective pore-volume constraints
A hemocompatible size selective polymer system comprising at least one polymer formed by polymerizing monomers in an organic phase dispersed in an aqueous phase, said aqueous phase comprises at least one dispersing agent, at least one free radical inhibitor and at least one buffering agent, said at least one polymer defining a porous structure, said porous structure consisting of pores with diameters in the range of 17 Angstroms to about 2000 Angstroms, said at least one polymer comprising transport pores with diameters from about 250 Angstroms to about 2000 Angstroms and effective pores with diameters greater than 100 Angstroms to about 250 Angstroms, and wherein said at least one polymer has a transport pore volume greater than about 1.8 to about 78% of a capacity pore volume and an effective pore volume greater than about 22 to less than about 98.2% of the capacity pore volume.
Across independent claims clm-00001, clm-00009, and clm-00017, the core claim coverage is the hemocompatible size selective porous polymer architecture defined by pore diameters and by quantitative transport and effective pore-volume fractions relative to capacity pore volume. Claim 9 and claim 17 further specify polymer formation conditions involving an organic phase dispersed in an aqueous phase with dispersing agent, free radical inhibitor, and buffering agent, while dependent claims refine component selections for crosslinking agent, dispersant, initiator, free radical inhibitor, buffering agent, and optional porogen.
Stated Advantages
Preferential adsorption of midsize proteins in whole blood while excluding larger proteins above about 50,000 Daltons.
High cytochrome-c selectivity together with capacity over a four-hour perfusion, with one adsorbent identified as having the best overall balance of selectivity and capacity.
Documented Applications
Extracorporeal blood purification including hemoperfusion/perfusion, with evaluation of adsorption performance over a four-hour perfusion.
Competitive adsorption against cytochrome-c and serum albumin in the context of size-selective adsorption of blood proteins.
Protein sorption in whole blood, including selective sorption of β2-microglobulin and cytokines while excluding albumin, hemoglobin, immunoglobulins, fibrinogen, serum proteins, and other blood proteins larger than 50,000 Daltons.
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