Biocompatibility; for extracting cytokines and beta-2-microglobulin
Inventors
Young, Wei-Tai • Albright, Robert L. • Golobish, Thomas D.
Assignees
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Publication Number
US-7875182-B2
Publication Date
2011-01-25
Expiration Date
Abstract
Size-selective hemocompatible porous polymeric adsorbents are provided with a pore structure capable of excluding molecules larger than 50,000 Daltons, but with a pore system that allows good ingress and egress of molecules smaller than 35,000 Daltons. The pore system in these porous polymeric adsorbents is controlled by the method of synthesis so that 98% of the total pore volume is located in pores smaller than 300 Angstroms (Å) in diameter with a working pore size range within 100 to 300 Å in diameter. The porous polymeric adsorbents of this invention are very selective for extracting midsize proteins, such as cytokines and β2-microglobulin, from blood and other physiologic fluids while keeping the components required for good health such as cells, platelets, albumin, hemoglobin, fibrinogen, and other serum proteins intact.
Core Innovation
The invention relates to a size-selective porous polymer comprising a plurality of pores, where all pores have diameters from greater than 100 Angstrom to about 300 Angstrom. The polymer is capable of sorbing protein molecules greater than 20,000 to less than 50,000 Daltons from blood while excluding the sorption of blood proteins greater than 50,000 Daltons.
The polymer includes an effective pore volume and a capacity pore volume, with the effective pore volume being from at least 0.306 cc/g to 0.986 cc/g and from at least 21.97% to 98.16% of the polymer’s capacity pore volume. The pore system is partitioned such that effective pores have diameters from greater than 100 Angstroms to about 250 Angstroms, and the polymer further has oversized pores with a diameter greater than 251 Angstroms.
The invention also defines polymers designed to sorb cytokines and β2-microglobulin and to exclude sorption of large blood borne proteins. The large blood borne proteins are selected from hemoglobin, albumin, immunoglobulins, fibrinogen, serum proteins, and other blood proteins larger than 50,000 Daltons.
Claims Coverage
The provided material includes three independent claims. Across these claims, the main inventive features focus on pore-size ranges, effective pore volume/capacity pore volume relationships, and blood-protein size selectivity for sorbing targeted proteins while excluding large proteins, with further targeting of cytokines and β2-microglobulin in one claim.
Pore diameters in the 100–300 Angstrom range with size-selective protein sorption
A size-selective porous polymer comprising a plurality of pores wherein all pores have diameters from greater than 100 Angstrom to about 300 Angstrom, the polymer being capable of sorbing protein molecules greater than 20,000 to less than 50,000 Daltons from blood and excluding sorption of blood proteins greater than 50,000 Daltons.
Effective pore volume and capacity pore volume relationship enabling selectivity
The polymer having an effective pore volume and a capacity pore volume, where the effective pore volume is from at least 0.306 cc/g to 0.986 cc/g and the effective pore volume is from at least 21.97% to 98.16% of the polymer’s capacity pore volume.
Effective pores (100–250 Angstrom) and oversized pores (>251 Angstrom)
Effective pores having diameters from greater than 100 Angstroms to about 250 Angstroms and the polymer having oversized pores with a diameter greater than 251 Angstroms.
Cytokine and β2-microglobulin sorption with exclusion of large blood borne proteins
A size selective polymer comprising a plurality of pores wherein all pores have diameters from greater than 100 Angstrom to about 300 Angstrom, the polymer designed to sorb cytokines and β2-microglobulin and exclude sorption of large blood borne proteins selected from hemoglobin, albumin, immunoglobulins, fibrinogen, serum proteins and other blood proteins larger than 50,000 Daltons.
Pore diameters in the >75–300 Angstrom range with protein sorption and exclusion
A polymer comprising a plurality of pores wherein all pores have diameters from greater than 75 Angstrom to about 300 Angstrom, the polymer being capable of sorbing protein molecules greater than 20,000 Daltons from blood and excluding sorption of blood proteins greater than 50,000 Daltons.
The independent claims collectively require a porous polymer with all pore diameters bounded within specific Angstrom ranges, a defined effective pore volume and its relationship to capacity pore volume, and a pore-size partition between effective pores (up to about 250 Angstroms) and oversized pores (>251 Angstroms). The polymers are described as sorbing protein molecules in the >20,000 to <50,000 Daltons range, including cytokines and β2-microglobulin, from blood while excluding sorption of proteins larger than 50,000 Daltons.
Stated Advantages
Provides size-selective sorption of protein molecules from blood in the >20,000 to less than 50,000 Daltons range.
Excludes sorption of blood proteins greater than 50,000 Daltons.
Enables sorption of cytokines and β2-microglobulin while excluding large blood borne proteins selected from hemoglobin, albumin, immunoglobulins, fibrinogen, serum proteins, and other proteins larger than 50,000 Daltons.
Shows little to no selectivity for adsorbing vitamins, glucose, electrolytes, fats, and other hydrophilic small-molecular nutrients carried by blood.
Documented Applications
No documented applications found
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