Liquid purification or separation – Processes – Separating
Reexamination Certificate
2000-12-19
2003-11-11
Drodge, Joseph (Department: 1723)
Liquid purification or separation
Processes
Separating
C210S650000, C210S651000, C210S243000, C210S645000, C210S504000, C210S500290
Reexamination Certificate
active
06645388
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to blood filter media and filters made therefrom, methods for making filter media, and methods for filtering leukocytes from blood using filter media.
BACKGROUND OF THE INVENTION
Many blood transfusions are performed each year in the United States and throughout the world. In connection with these transfusions, the drawn blood of a donor is routinely filtered so as to remove much of the leukocyte component. In this regard, donor leukocytes are known to cause adverse reactions to blood transfusion recipients. For example, donor leukocytes can cause Human Leukocyte Antigen formation (HLA sensitization) if a blood recipient is exposed to a large quantity of leukocytes in the donated blood. Leukocytes may also induce graft versus host reactions in the blood recipients. These are serious conditions, especially for immuno-compromised patients. These individuals, such as those suffering from various forms of Leukemia, typically receive multiple blood transfusions each year. Therefore, the risks of being exposed to such adverse reactions are amplified in such individuals.
Additionally, at this time there is no known benefit in transfusing donor leukocytes to a recipient. Human blood typically contains 10
9
leukocytes per unit (that is approximately 450 mL of blood). A typical transfusion occurrence requires two or more units of blood. Thus, it is not uncommon for a patient to receive as much as 10
10
white cells in a single transfusion episode, if the blood is not filtered to remove the leukocyte component. It should be noted however, that typically whole blood is filtered or treated in various ways (such as by irradiation) in order to prepare it for transfusion.
In the past, if whole blood or one of the blood components was filtered for leukocytes, the filter typically would end up removing a sizable proportion of another useful blood component, such as the platelets, which may also be attracted to the leukocyte filter. Currently, whole blood is first separated into its components before each component is leuko-depleted, that is filtered of leukocytes. These components are principally (a) packed red blood cells (PRBCs), (b) platelet concentrates and (c) non cellular components i.e. plasma. It would therefore be advantageous and efficient to have a means to leuko-deplete whole human blood before separating the blood into its three known major useful components. Once the leukocytes were filtered out, the whole blood itself could then be used as it is in a blood transfusion process, or if required, individual blood components could be used.
As has already been stated, an efficient method for the leuko-depletion of whole human blood requires the ability to selectively remove leukocytes while recovering red blood cells, platelets and plasma. Typical blood filters rely on mechanical sieving provided by a gradient of the porosity of the filter medium. Centrifugation is also used to separate blood components with different specific gravities. It would also be very desirable if one could use specific interactions between leukocytes and the filter medium to selectively remove the white blood cells from the blood without substantially affecting other cellular components in the blood.
In this regard, there have been three families of adhesion receptors that have been identified for leukocyte rolling, these being the integrins, immunoglobulin-related molecules and selectin molecules. For the purposes of this application, leukocyte rolling means the shear-induced movement of leukocytes that is mediated by adhesion receptors such as integrins and selecting. Integrins are a large family of glycoproteins that attach cells to ligands on surfaces such as those of other cells or surrounding media (for example a filter medium). These receptors have been used to design media that selectively removes leukocytes from whole human blood. Typically, rolling occurs at or below the velocity of the freely flowing cells and in the same direction of the free flowing cells.
In this regard, European Patent Application EP0792677A1 to Haddock provides background on how the adhesion properties of leukocyte surfaces to ligands can be used to design a blood filter that selectively removes leukocytes, while allowing the red cells and the platelets of whole human blood to go through the filter substantially unaffected. Specifically, the application describes how immobilizing carbohydrate ligands such as fucoidan or D-mannose-6-phosphate on functionalized slides enhances binding and aggregation of leukocytes (specifically L-selectins of the leukocytes) on the surface. However, this immobilization method involves functionalizing partially hydrolyzed polyester surfaces with ethylene glycol diglycidyl ether, resulting in epoxy-terminated groups. The epoxy groups are then used to immobilize saccharides in a following step. Such a method involves multiple steps, is laborious and would likely be costly to implement.
Surface treatments such as grafting or coating membranes or nonwoven materials have been used to make filters that are capable of removing leukocytes from whole blood. For example U.S. Pat. No. 4,936,998 to Nishimura et al. discloses a surface coating using acrylic copolymers. Grafting acrylates on surfaces is disclosed in U.S. Pat. No. 4,880,548 to Pall et al. U.S. Pat. No. 5,288,403 to Ohno discloses the use of copolymers containing glucoxyethyl methacrylate coated polyester nonwoven filters with a 99% leukocyte reduction from platelet concentrates. The patent does not discuss the capability of leuko-depleting whole human blood where a large number of red blood cells are present. Also, the described coating is not crosslinked. Consequently there is a risk of potential leaching associated therewith.
U.S. Pat. No. 5,783,094 to Krause et al. discloses coating methods that use a polysaccharide that is claimed to efficiently remove leukocytes from platelet concentrates. These polysaccharides are described as generally water-soluble, and therefore would not likely be suitable for filtration of water-based fluids. The patent describes the further use of a melamine, a cancer suspect/irritant agent, as a secondary crosslinking agent. The efficiency of the filters is described to be in the range of 2+ log reduction for leukocytes, only when non-crosslinked material is used. When crosslinked, the leukocyte depletion efficiency drops below 2 logs, which is traditionally unacceptable for blood transfusions.
U.S. Pat. No. 5,895,575, also to Krause et al., uses the same approach for developing platelet and whole blood filters. Again, non-crosslinked filters show remarkable efficiency, but with the danger of leaching and contaminating the blood. When filters with the crosslinked polysaccharide coating are used, leukodepletion efficiency of whole blood remains high but with slow filtration rates.
Thus, despite the availability of processes to filter leukocytes from whole blood, there is still a need for a filtration process and filter for filtering whole blood of leukocytes, which achieves at least a 3 log leukocyte reduction. Further, there is a need for such a filter which achieves no leaching of the filter coating (i.e. that is crosslinked and has the ability to withstand a thorough wash), and a filtration rate that allows filtration of a unit of blood to be completed within an acceptable time frame. In this regard, a typical bedside transfusion is completed in a period of sixty to one hundred and twenty minutes per unit of blood.
There is also a need for the use of safe crosslinking agents rather than cross linking agents with potentially negative health ramifications which may add additional possibility of danger of a reactive chemical leaching into the transfused blood. Further, there is also a need for blood filter coatings utilizing a crosslinking process that is intramolecular, i.e., the polymer used to coat the substrate is a self-crosslinking one. Finally, there is a need for a highly porous filtration system that contains only nonwoven materials with porosity greater t
Drodge Joseph
Flack Steven D.
Kimberly-Clark Corporation
Menon Krishnan
Robinson James B.
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