Filters for removing substances from blood

Abstract

A blood filter for enhanced leukopenia with platelet recovery is disclosed. The filter includes a non-woven porous filter coated with an acetone copolymer solution.

Description

[Technical field]

[0001] The present disclosure relates generally to filters for removing substances such as selected components and / or impurities from bodily fluids such as blood. More particularly, the present disclosure is directed to blood filters that effectively remove undesirable components such as white blood cells while allowing for effective recovery of desirable blood components such as platelets. Even more particularly, the present disclosure is directed to blood filter assemblies including such filters, and methods for making such filters and filter assemblies. [Background technology]

[0002] Using a variety of manual and automated systems and methods, whole blood is collected and often separated into its clinical components (typically red blood cells, platelets, and plasma). The whole blood or collected components are typically stored separately and used to treat a variety of specific conditions or medical conditions.

[0003] Before blood or collected blood components ("blood products") are transfused to a recipient in need of the component, it is often desirable to minimize the presence of impurities or other substances that may cause undesirable side effects in the recipient. For example, it is commonly considered desirable to reduce the number of white blood cells in the blood product before storage, or at least before transfusion, due to possible reactions (i.e., "leukopenia").

[0004] Filters are widely used today to achieve leukocyte reduction of blood products (e.g., warm and cold filtration of leukocytes from whole blood, red blood cell, and / or platelet products). Filters typically include a filtration media disposed between mating walls of a filter housing. Inlet and outlet ports associated with the housing provide flow paths to and from the interior of the filter. The walls of the housing can be made of a rigid, typically plastic, material, or a flexible material (typically PVC). Due to the importance of filtering blood or blood components, there is a continuing desire to improve the structure and performance of biological fluid filters. Summary of the Invention

[0005] In one aspect, the present disclosure relates to a filtration medium for removing substances from blood. The filtration medium includes a porous polymeric nonwoven material for removing selected components from blood and recovering other selected components. The filtration medium includes a coating applied to the porous polymeric material.

[0006] In another aspect, the present disclosure is directed to a blood filter assembly including a housing having an inlet and an outlet, a pre-filter, a post-filter, and a filtration medium disposed between the pre-filter and the post-filter, the filtration medium including one or more sheets of the filtration medium described above.

[0007] In a further aspect, the present disclosure is directed to a method of making a filter for removing substances from blood, the method comprising forming a fabric sheet made of a material comprising a polyether-ester copolymer, and coating at least one side of the fabric sheet with a coating solution that is a copolymer of vinyl acetate and vinylpyrrolidone. [Brief description of the drawings]

[0008] [Figure 1] FIG. 1 is a front view of an exemplary filter assembly according to the present disclosure.

[0009] [Diagram 2] 2 is a side cross-sectional view of the filter assembly of FIG. 1 taken along line 2-2.

[0010] [Diagram 3] FIG. 2 is an exploded view of the filter assembly of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present disclosure relates generally to filters for removing selected components from blood. The term "blood" includes whole blood and blood components, such as red blood cells, separated from whole blood. The filters described herein are particularly suited for (but not limited to) filtering whole blood.

[0012] FIG. 1 illustrates one embodiment of a filter assembly according to the present disclosure. The filter 10 is suitable for removing selected components and / or impurities from a biological fluid, such as blood. The filter assembly 10 includes a housing 12 including outer walls 14, 16 (FIG. 2). The housing 12, and indeed the filter 10, are preferably made of a biocompatible material that can also be sterilized using conventional sterilization techniques commonly used in the assembly of disposable blood processing sets, such as autoclaving, gamma radiation and / or electron beam. In one embodiment, the housing walls 14, 16 may be made of a rigid polymeric material that is sealed at or near its periphery. Sealing of the walls 14, 16 may be achieved by adhesive, welding, or other forms of hermetic attachment.

[0013] In a preferred embodiment, as shown in Figures 1 and 2, the housing walls 14, 16 can be made of a soft, flexible polymeric material. Examples of suitable polymeric materials for the housing walls 14, 16 include polyvinyl chloride and / or polyolefins. As shown in Figures 1 and 2, the housing walls 14, 16 can be bonded along their periphery to form a seal 18. In the embodiment of Figures 1 and 2, an additional inner periphery seal 20 can also be provided, as described in U.S. Patent Application Publication No. 2002 / 0113003, the contents of which are incorporated herein by reference. The seals 18, 20 define a cushioned periphery.

[0014] Typically, a filter assembly of the type described herein can be included as part of a disposable fluid processing set or kit, in its most basic form, biological fluid is introduced from a connected or pre-connected source, passes through the filter 10, and after passing through the membrane is collected in a pre-attached container, with undesirable components being captured by the filtration media. Thus, the walls 14, 16 can include inlet and outlet ports 24, 26, respectively, to allow for the introduction and discharge of fluid. The ports 24, 26 communicate with the interior chamber defined by the housing walls 14, 16. The ports 24, 26 can be carried by the walls 14, 16, as shown in Figures 1 and 2. The ports 24, 26 can be separately attached to the housing walls 14, 16 or integrally molded with the housing walls 14, 16. As shown in Figures 1 and 2, the inlet and outlet ports 24, 26 can be arranged in diametrical relationship on the walls 14, 16. Thus, for example, inlet port 24 may be located closer to the "top" periphery 13 of filter 10 on wall 14, and outlet port 26 may be located closer to the "bottom" periphery 15 of filter 10 and wall 16. Of course, it will be understood that the relative locations of ports 14, 16 may be otherwise modified or provided. Ports 24, 26 define an internal flow path that establishes fluid communication between an internal chamber and tubing 27 that leads to other containers or components of a disposable processing set in which filter 10 is contained.

[0015] As shown in Figures 2-3, the housing walls 14, 16 contain a filtration medium 30. In one embodiment, the filter 30 may be provided as a pad including multiple stacked sheets having pores sized to prevent the passage of white blood cells while allowing the passage of other desirable blood components, such as red blood cells and platelets. In one embodiment, as shown in Figure 2, the filter 30 may include multiple sheets 31, each sheet 31 including pores of a desired diameter and / or size and distribution. In one embodiment, the sheets 31 may be made of meltblown nonwoven fibers. In accordance with the present disclosure, the fibers may be made from a suitable polymeric material, which will be described in more detail below.

[0016] As shown in FIG. 3, the filter 30 can be made of multiple meltblown nonwoven fibrous sheets. Additionally, a group of sheets can provide a filtration medium with filter portions selected to perform specific functions. For example, the filter 30 can include a filter portion made up of multiple sheets, with the sheets making up the filter portion 32 and / or the portion 32 adjacent or closest to the housing wall 14 and inlet port 24 having a selected porosity that provides for the removal of micro-agglomerates and smaller sized particles. While FIG. 3 shows two sheets (for illustrative purposes only), the portion 32 can include one or more sheets, typically, but not limited to, one to five sheets to provide a "pre-filter."

[0017] Filtration media 34 may provide a primary or main filter, and may also include multiple sheets of a selected porosity. Although only five are shown (for illustrative purposes only), the number of sheets making up the primary or main filter may be anywhere from 10 to 40, with each sheet having a thickness of about 10 μm to about 500 μm. In one embodiment, about 30 sheets may be included in filtration media 34.

[0018] The filter portion 36 may provide additional component filtration and / or function as a spacer element between the filtration media 34 and the housing wall 16. The filter portion 36, which may also include multiple sheets (although only one sheet is shown for illustrative purposes only), is located downstream of the filtration media 34 closer to the housing wall 16 and the outlet port 26 and may be referred to as a "post-filter." As seen in FIG. 2, the filter portions 32, 34, 36 may be joined together and sealed together to provide a single filter pad. Alternatively, some or all of the individual sheets of each of the filter portions 32, 34, 36 may be joined together and sealed with the housing walls 14, 16 with the inner seal 20 as shown in FIG.

[0019] Filtration medium 34 may be a nonwoven material made from meltblown fibers, as described in U.S. Patent No. 7,736,516, which is incorporated herein by reference in its entirety. As described therein, each sheet of filtration medium 34 may be made of a suitable polymeric material, such as a polyether-ester copolymer (PEC).

[0020] The polyether-ester copolymers can be obtained by polycondensation in the melt of at least one alkylene glycol, at least one aromatic dicarboxylic acid or ester thereof, and a polyalkylene oxide glycol. The alkylene glycol can contain from 2 to 4 carbon atoms, the preferred glycol being butylene glycol.

[0021] Suitable aromatic dicarboxylic acids include terephthalic acid, 1,4-naphthalenedicarboxylic acid and 4,4'-diphenyldicarboxylic acid.

[0022] Preferred polyalkylene oxide glycols include polybutylene oxide glycol, polypropylene oxide glycol and polyethylene oxide glycol, or combinations thereof. Particularly preferred are polypropylene oxide (PPO) / polyethylene oxide (PEO) block copolymers.

[0023] The resulting polymer has a backbone constructed from rigid segments (hydrophobic) of repeating units derived from an alkylene glycol (preferably 1,4-butanediol) and an aromatic dicarboxylic acid (preferably terephthalic acid or dimethyl terephthalate), and has flexible hydrophilic segments derived from a polyalkylene oxide glycol.

[0024] The resulting preferred polymer structure is as follows: [ka]

[0025] Suitable polyalkylene oxide glycols are commercially available: Pluronic PE6002™ is a polypropylene oxide end-capped with ethylene oxide glycol (ethylene oxide:propylene oxide = 36 / 64 weight ratio) from Basf.

[0026] The copolyetheresters described herein are either commercially available or can be prepared according to known polycondensation processes, preferably according to the process described in U.S. Pat. No. 6,441,125, incorporated herein by reference, by polycondensation in the melt of the above components in the presence of a catalyst based on a combination of titanium and a divalent metal in a single compound or a combination of compounds containing titanium and a divalent metal, the molar ratio of titanium to the divalent metal being preferably less than 1.5.

[0027] The divalent metal is preferably an alkaline earth metal, preferably magnesium. The titanium is preferably in the form of a metal-organic compound such as a titanium alkoxide or a titanium ester.

[0028] According to the present disclosure, the copolyether-esters described herein can be processed by meltblowing to obtain fibers having diameters in the range of less than 6 μm, preferably less than 3 μm, with the preferred average diameter being in the range of 1.8 to 2.2 μm.

[0029] The amount of polyalkylene oxide glycol in the copolyetherester is preferably in the range of 0.1 to 20% by weight, or 0.03 to 6% by weight of the polyethylene oxide.

[0030] Leukocyte reduction and / or platelet recovery by the filtration medium can be further enhanced by coating the surface of the filtration medium 34 (or each sheet thereof) with a coating solution. The coating solution may be a polymeric solution of hydrophobic and hydrophilic monomers. If It may be a polymer obtained by a reaction.

[0031] Examples of suitable hydrophobic monomers that can be used in the coating solution include vinyl esters, such as vinyl acetate; alkenes, such as ethylene, propylene, hexane-1, heptene-1, vinylcyclohexane, 3,3-dimethyl-1-propene, 3-methyl-1-diisobutylene, 4-methylpentene-1; and alkyl (meth)acrylates derived from saturated alcohols, such as methyl acrylate, ethyl (meth)acrylate, propyl (meth)acrylate, n-butyl (meth)acrylate, tert-butyl (meth)acrylate, methacrylates incorporating methacrylates and acrylates, and mixtures of both.

[0032] Examples of suitable hydrophilic monomers include monomers with acid groups, such as vinylphosphonic acid, vinylsulfonic acid, acrylic acid and methacrylic acid; monomers with basic groups, in particular vinylpyridine, 3-vinylpyridine, 2-methyl-5-vinylpyridine, 3-ethyl-4-vinylpyridine, 2,3-dimethyl-5-vinylpyridine, N-vinylpyrrolidone, 2-vinylpyrrolidone, N-vinylpyrrolidine, 3-vinylpyrrolidine; monomers with polar groups, such as 2-methacryloxyethyl phosphorylcholine, vinyl alcohol, which can be obtained after polymerization by saponifying vinyl esters.

[0033] More specific examples of suitable coating polymers / copolymers include, but are not limited to, N-vinyl-2-pyrrolidone (NVP) and vinyl acetate (VAc), 2-hydroxyethyl methacrylate (HEMA) and vinyl acetate (VAc), N-vinyl-2-pyrrolidone and 2-ethoxyethyl methacrylate (2-EMMA), N-vinyl-2-pyrrolidone (NVP) and methyl methacrylate (MMA), vinyl alcohol (VA) and vinyl acetate (VAc).

[0034] In one embodiment, the coating solution may be a solution of the selected polymer or copolymer in acetone. In a more particular embodiment, the coating solution may be a solution of a vinyl acetate and vinyl pyrrolidone (VA / VP) statistical copolymer. The weight ratio of vinyl acetate to vinyl pyrrolidone may be between 10:1 and 4:1, more preferably between 9:1 and 5:1, and even more preferably between 8:1 and 6:1. In one embodiment, the weight ratio of vinyl acetate to vinyl pyrrolidone (VA / VP) may be 7:1. For example, the coating solution may include 87.5% vinyl acetate and 12.5% ​​vinyl pyrrolidone by weight. Other copolymer solutions may also be used to coat the filtration medium 30 and enhance one or both of leukocyte reduction and platelet recovery. Further properties of the coating solutions described above are described in U.S. Pat. No. 7,775,376, the contents of which are incorporated herein by reference.

[0035] The sheet of nonwoven filtration media can be immersed in a bath of acetone coating solution for a time sufficient to coat both sides of the filtration media 34. The coating solution preferably contains about 1-5% polymer, more preferably 1-3% polymer solution, or more preferably 2% (95%-99% by weight acetone, more preferably 97-99% or more preferably 98% by weight acetone). After immersion, excess coating solution is removed by dripping off the surface of the media, and the filtration media is dried for a selected time and / or at a selected drying temperature. Drying can be accomplished in an oven or by using drying drums in a manner recognized by those skilled in the art. In one embodiment, the filtration media can be dried at a temperature of 54° C. to 111° C. for about 3-7 seconds, preferably about 5 seconds.

[0036] After the roll of coated filtration media (fabric) is dried, the roll may be cut into individual sheets 31. A plurality of these individual sheets can be stacked and combined with pre-filter and / or post-filter sheets to arrive at a filter pad for inclusion in a filter assembly as shown in FIG. 1. Coated filters made according to the above methods further enhance leukocyte reduction and platelet recovery. Shown below are test results that demonstrate the improved leukocyte reduction and platelet recovery properties of the coated filters described herein. EXAMPLES

[0037] Small-scale filter (soft housing, square, surface area 15cm 2) was manufactured with 20 layers of fabric (20 layers of filtration media, 3 layers of pre-filter and 1 layer of post-filter, the pre-filter contained 1 layer of spunbond PET and 2 layers of non-woven meltblown PBT, and the post-filter contained 1 layer of spunbond PET). Two different filtration media, described below, "control" and "PEC sample", were compared. The control was made of standard PBT combined with VAVP coated polymer (VA / VP weight ratio 7, 0.22% w / w in acetone) and the PEC sample included PEC fabric combined with VAVP coated polymer (VA / VP weight ratio 7, 2% w / w in acetone).

[0038] Blood units were collected from informed donors in PVC bags containing 70 mL of CPD (500 mL ± 10%, excluding CPD). After collection, blood bags were stored on a butane-1,4-diol cooling plate at room temperature for up to 24 h. Before filtration, collected blood was connected to a filter system. Three filtrations were performed for each bag (160 g of blood collected for each filter). Filtration was performed by gravity.

[0039] Samples were collected from the blood bags before and after filtration to assess white blood cell (WBC) removal and platelet (PLT) recovery (cell counting by Sysmex KX-21N automated hematology analyzer). White blood cells in the filtered blood were counted by flow cytometry. Total filtration time during the 160 g blood draw was also measured. The results are shown in Table 1 below. [Table 1]

[0040] As shown in Table 1, the use of coated PEC as a fabric material improves the ability to recover platelets while providing adequate leukocyte removal and reduced filtration times compared to other fabrics coated with the coating solutions described herein.

[0041] It will be understood that the above-described embodiments are illustrative of some of the applications of the principles of the present subject matter. Numerous modifications may be made by those skilled in the art without departing from the spirit and scope of the claimed subject matter, including combinations of features individually disclosed or claimed herein. For these reasons, the scope of the invention is not limited to the above description, but is set forth in the appended claims.

Claims

1. a porous polymeric nonwoven fabric for removing selected components from blood and recovering other selected components, the fabric comprising a nonwoven material comprising a polyether-ester copolymer having hydrophilic and hydrophobic segments; a coating applied to the fabric of a porous polymer; The copolymer comprises the following polymer structure: 【Chemistry 1】 A filtration medium for removing substances from blood, the coating comprising an acetone solution containing a copolymer of vinyl acetate and vinylpyrrolidone.

2. 2. The filtration media of claim 1, wherein the hydrophobic segment comprises repeating units derived from an alkylene glycol and at least one aromatic dicarboxylic acid or ester.

3. 3. The filtration media of claim 1 or claim 2, wherein the hydrophilic segment is derived from at least one polyalkylene oxide glycol.

4. 4. The filtration medium of claim 1, wherein the coating is obtained by a polymerization reaction of hydrophobic and hydrophilic monomers.

5. the hydrophobic monomer is selected from the group consisting of vinyl esters, alkenes and alkyl methacrylates; 5. The filtration medium of claim 4, wherein the hydrophilic monomer is selected from the group consisting of monomers having an acid group, monomers having a basic group, and monomers having a polar group.

6. 6. The filtration medium of any one of claims 1 to 5, wherein the ratio of vinyl acetate to vinylpyrrolidone is from 10:1 to 4:

1.

7. a housing including an inlet and an outlet; A pre-filter and After filter, A blood filter assembly comprising a filtration medium located between the pre-filter and the post-filter, the filtration medium comprising one or more sheets of the filtration medium of any one of claims 1 to 6.

8. The blood filter assembly of claim 7 , wherein the filtration media comprises a stack of a plurality of the sheets of the filtration media.

9. forming a fabric sheet comprising a polyether-ester copolymer; The copolymer comprises the following polymer structure: 【Chemistry 1】 and coating at least one side of said fabric sheet with a coating solution comprising a copolymer of vinyl acetate and vinylpyrrolidone.

10. The method of claim 9 , wherein the coating comprises immersing the fabric in a bath of the coating solution.

11. The method of claim 10 further comprising removing excess coating solution from the fabric sheet.

12. The method of claim 11 further comprising drying the coated fabric sheet at a temperature of from 54 to 111°C.

13. The method of any one of claims 9 to 12, comprising forming the fabric from meltblown fibers made from the polyether-ester copolymer.

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