CN116635135A - Polymer film - Google Patents

Abstract

The present application relates to a polymer film. The film may comprise a polymeric film made from a polymer selected from the group consisting of aromatic sulfone polymers, polyamides, celluloses, cellulose acetates, polymethyl methacrylates, polyvinyl alcohols, and polyacrylonitriles, wherein the polymeric film has a major surface; stilbenes, isoflavones or flavones coated on the major surface of the polymer film.

Description

polymer film

technical field

The present disclosure relates to a microporous membrane. Furthermore, the present disclosure relates to a method for producing such membranes. The present disclosure also relates to the use of such membranes for filtering and purifying liquid media.

Background technique

Polymer membranes are used in a very wide variety of different industrial, pharmaceutical or medical applications for precision filtration. In these applications, membrane separation methods are becoming more and more important, since these methods offer the advantage that the substances to be separated are not thermally burdened or even damaged. Ultrafiltration membranes can be used to remove or separate large molecules. Many further applications of membrane separation methods are known in the beverage industry, biotechnology, water treatment or sewage technology. Such membranes are usually classified according to their retention capacity, ie according to their capacity to retain particles or molecules of a certain size, or with regard to the effective pore size, ie the size of the pores which determines the separation behaviour. Thus, ultrafiltration membranes encompass the pore size range between approximately 0.01 μm and about 0.1 μm that governs the separation behavior such that particles or molecules with sizes in the range greater than 20,000 Daltons or greater than about 200,000 Daltons may be retained. This requires better polymer films.

Contents of the invention

Accordingly, in one aspect, the present disclosure provides a membrane comprising: a polymer membrane made of a polymer selected from the group consisting of aromatic sulfone polymers, polyamides, cellulose, cellulose acetate, polymethylmethacrylate , polyvinyl alcohol and polyacrylonitrile, wherein the polymer film has a major surface; stilbenes, isoflavones or flavones coated on the major surface of the polymer film.

In another aspect, the present disclosure provides a method comprising: forming a polymer membrane from an aromatic sulfone polymer; and coating a stilbene, isoflavone, or flavone to a hollow fiber membrane.

In another aspect, the present disclosure provides the use of the polymeric membrane of the present disclosure for filtering liquids.

Detailed ways

Before any embodiments of the present disclosure are explained in detail, it is to be understood in this application that the invention is not limited to the details of use, construction and arrangement of parts set forth in the following description. The invention is capable of other embodiments and of being practiced or carried out in various ways that will become apparent to those of ordinary skill in the art upon reading this disclosure. Also, it is to be understood that the phraseology and terminology used herein are for the purpose of description and should not be regarded as limiting. The use of "comprising", "comprising" or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. It is to be understood that other embodiments may be utilized and structural or logical changes may be made without departing from the scope of the present disclosure.

The present disclosure provides a membrane comprising a polymeric membrane having a major surface and a wall having a wall thickness. In some embodiments, the polymeric membrane may be a hollow membrane, and the hollow membrane may have a continuous hollow lumen extending from one end of the fiber to the other, an outwardly facing outer surface forming the outer side of the fiber; an inner surface of the hollow lumen, the inner surface delimiting the continuous hollow lumen; and an intermediate wall having a wall thickness. In some embodiments of hollow membranes, the major surface may be an inner surface. In some embodiments of hollow membranes, the major surface may be an inner surface. The polymer film may include stilbenes, isoflavones, or flavones coated on a major surface of the polymer film. In some cases, stilbenes, isoflavones, or flavones can form a layer and can at least partially cover a major surface. In some embodiments, the stilbenes, isoflavones, or flavones may cover greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%. In some embodiments, the stilbenes, isoflavones, or flavones may cover 100% of the major surface of the polymer film. In some embodiments, the wall can include a plurality of pores, and the stilbene, isoflavone, or flavone can be coated on the surface of at least some of the plurality of pores. In some embodiments, the stilbenes, isoflavones, or flavones may cover greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95% of the surface of at least some of the plurality of wells , 96%, 97%, 98%, or 99%. In some embodiments, the stilbenes, isoflavones, or flavones may cover 100% of the surface of at least some of the plurality of wells. In some embodiments, greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% of the surface. In some embodiments, the stilbenes, isoflavones, or flavones may cover the surface of all of the plurality of wells. In some embodiments, a stilbene, isoflavone, or flavone can be coated on and cover at least a portion of the outer surface. In some embodiments, stilbenes, isoflavones, or flavones may cover greater than 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% of the outer surface % or 99%. In some embodiments, stilbenes, isoflavones, or flavones may cover 100% of the outer surface. In some embodiments, the polymeric film can be a flat sheet film having two major surfaces: a first major surface and a second major surface opposite the first major surface. In some of these embodiments, the stilbenes, isoflavones, or flavones can at least partially cover both the first major surface and the second major surface. In some of these embodiments, the stilbenes, isoflavones, or flavones may cover greater than 50%, 60%, 70%, 75%, 80%, 85%, 90% of both the first major surface and the second major surface. %, 95%, 96%, 97%, 98%, or 99%.

The wall thickness (in embodiments of hollow fiber membranes, the wall thickness may be measured between the outer and inner surfaces of the hollow fiber membranes) may range from 20 μm to 500 μm, 140 μm to 400 μm, 150 μm to 380 μm, or 160 μm to 380 μm. In some embodiments, in order to achieve the desired flow rate through the lumen of the hollow fiber membrane according to the present disclosure, especially the favorable pressure drop, it is preferred that the inner diameter of the hollow fiber membrane as described herein is between 100 μm and 2000 μm, 700 μm to 2000 μm, 800 μm to 1800 μm, or 900 μm to 1600 μm. The wall thickness and diameter (in the case of hollow fiber membranes, the inner or lumen diameter, and the outer diameter) of the membranes as described herein are also examined by conventional methods, such as using a scanning electron microscope, for example, at a magnification of 400:1 or transmission electron microscopy (SEM or TEM, respectively).

Polymer films according to the present disclosure may be prepared by the methods disclosed in WO 2019/229667 A1 (Malek et al.), which is incorporated by reference in its entirety into this disclosure. In some embodiments, polymeric membranes can be made from homogeneous spinning solutions of polymeric components and solvent systems. Thus, the polymer component comprises a polymer selected from the group consisting of aromatic sulfone polymers, polyamides, cellulose, cellulose acetate, polymethyl methacrylate, polyvinyl alcohol and polyacrylonitrile. The polymer component may also comprise at least one hydrophilic polymer. Flat sheet films and their preparation are described, for example, in EP 0361 085 B1.

According to the present disclosure, the concentration of sulfone polymer in the spinning solution is preferably in the range of 17% to 27% by weight. Below a concentration of 17% by weight, disadvantages may arise, especially with regard to the mechanical stability of the resulting hollow fiber membranes. On the other hand, membranes obtained from spinning solutions with more than 27% by weight of sulfone polymer may exhibit an overly dense structure and insufficient permeability. The spinning solution preferably comprises 20% to 25% by weight of the hydrophobic aromatic sulfone polymer. The sulfone polymers may also contain additives such as antioxidants, nucleating agents, UV absorbers, etc. to selectively alter the properties of the membrane.

Advantageous hydrophobic aromatic sulfone polymers constituting the membranes according to the present disclosure or used in the process according to the present invention are polysulfones, polyethersulfones, polyphenylenesulfones or polyaryl ethersulfones. Preferably, the hydrophobic aromatic sulfone polymer is polysulfone or polyethersulfone having repeating molecular units as shown in the following formulas (I) and (II):

Long-chain polymers are advantageously used as the at least one hydrophilic polymer, which on the one hand exhibit compatibility with hydrophobic aromatic sulfone polymers and which have repeating polymer units which are inherently hydrophilic. Preference is given to using hydrophilic polymers with an average molecular weight M _W of greater than 10,000 Daltons, preferably greater than 20,000 Daltons, more preferably greater than 30,000 Daltons. The hydrophilic polymer is preferably polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, polyglycol monoester, polysorbate such as polyoxyethylene sorbitan monooleate, carboxymethylcellulose Or modifications or copolymers of these polymers. Polyvinylpyrrolidone and polyethylene glycol are particularly preferred.

In the context of the present disclosure, the at least one hydrophilic polymer may also comprise a mixture of different hydrophilic polymers. For example, the hydrophilic polymers may be chemically different hydrophilic polymers or a mixture of hydrophilic polymers having different molecular weights, for example a mixture of polymers differing in molecular weight by a factor of 5 or more. Preferably, said at least one hydrophilic polymer comprises a mixture of polyvinylpyrrolidone or polyethylene glycol with a hydrophilically modified aromatic sulfone polymer. It is also preferred that the hydrophilically modified aromatic sulfone polymer is a sulfonated aromatic sulfone polymer, especially a sulfonated modification of a hydrophobic aromatic sulfone polymer for use in the membranes and methods of the present disclosure thing. Mixtures of polyethersulfone, sulfonated polyethersulfone and polyvinylpyrrolidone can be used with particular advantage. As a result of the presence of the hydrophilically modified aromatic sulfone polymers, hollow fiber membranes with particularly stable hydrophilic properties in use can be obtained.

Stilbenes, isoflavones or flavones can then be coated on the major surfaces of the polymer film made from the aromatic sulfone polymer. Stilbenes, isoflavones or flavones may be dissolved in solvents to form coating solutions. The solvent may be selected from the group consisting of ethanol and isopropanol. In some embodiments, stilbenes, isoflavones, or flavones may be dissolved in a solvent at less than 1%, less than 0.9%, less than 0.8%, less than 0.7%, less than 0.6%, or less than 0.5% by weight in a solvent at room temperature to prepare coating solutions. In some embodiments, a coating solution may be prepared by dissolving stilbenes, isoflavones, or flavones in a solvent at 0.8%, 0.7%, 0.6%, 0.5%, or 0.4% by weight in a solvent. The polymer film can be impregnated with a coating solution. After impregnating the polymer film with the coating solution and incubating for a certain period of time (eg, 10 minutes), the coating solution can be drained from the polymer film. After immersing the polymer film in the coating solution and incubating for a certain period of time (eg, 10 minutes), the coating solution is drained from the polymer film. To dry the polymer film, the polymer film can be connected to a nitrogen source which applies a gentle air flow through the film, thereby evaporating the solvent and leaving the stilbenes, isoflavones or flavones coated on the major surface of the polymer film.

In a hollow fiber membrane embodiment, the coating solution can be flowed into the lumen of the hollow fiber membrane. Due to the very good wettability of the solvent on the aromatic sulfone polymer fibers, the coating solution can cover the membrane wall and also enter the extracapillary volume in small amounts. After the lumen is completely filled with the coating solution and incubated for a certain period of time (eg, 10 minutes), the coating solution can be drained from the hollow fiber membranes. After this step, the hollow fiber membranes are still completely saturated with the coating solution due to capillary forces.

(Isoflavones) used in the present application may include those disclosed in US 8,883,010 B2 (Chandrasekaran et al.), such as flavones, isoflavones or combinations thereof. Exemplary (isof)flavones can be isolated, naturally occurring isoflavones, synthetic isoflavones, or combinations thereof. In exemplary embodiments, the flavone or isoflavone may be a hydroxy(is)flavone (i.e., hydroxyflavone or hydroxyisoflavone) having at least one hydroxyl group, such as a polyphenol, i.e., a molecule having at least two phenolic groups . Although not fully understood, it is believed that the phenolic groups in the hydroxy(is)flavones contribute to the antioxidant properties of the hydroxy(is)flavone molecule and facilitate retention of the molecule in the matrix.

In one embodiment, the (is)flavones may include at least one of hydroxyflavones and hydroxyisoflavones. Hydroxyflavones or hydroxyisoflavones can be mono-, di-, tri-, or tetra-hydroxyisoflavones (ie, 1, 2, 3, or 4 hydrogens of the flavone or isoflavone molecule are replaced by hydroxyl groups), such as trihydroxy isoflavones. The hydroxyflavones or hydroxyisoflavones may also contain one or more additional substituents, such as alkoxy and/or glucose moieties. In one embodiment, the phytochemical comprises a hydroxyisoflavone, such as a mono-, di- or trihydroxyisoflavone.

In one embodiment, the hydroxyisoflavones are substituted derivatives of isoflavones, related to the isoflavone molecule by replacing one, two, three or four hydrogen atoms with hydroxyl groups. In some embodiments, the isoflavone structure may additionally be substituted with one or more alkoxy groups, such as methoxy or ethoxy groups.

Exemplary hydroxyisoflavones may be selected from:

Genistein (5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one, also known as 4',5,7-trihydroxyisoflavone) with the following structure:

· Daidzein (7-hydroxy-3-(4-hydroxyphenyl)chromen-4-one (IUPAC), or 4',7-dihydroxyisoflavone) having the following structure:

Glyzein (7-hydroxy-3-(4-hydroxyphenyl)-6-methoxy-4-benzopyrone (IUPAC), or 4',7-dihydroxy-6-methoxy isoflavones),

·Pheraxanthin (5-hydroxy-3-(4-hydroxyphenyl)-7-methoxybenzopyran-4-one, or 4',5-dihydroxy-7-methoxyisoflavone) ,

Chickitein A (5,7-dihydroxy-3-(4-methoxyphenyl)chromen-4-one or 5,7-dihydroxy-4'-methoxyisoflavone) ,

Orobol (3-(3,4-dihydroxyphenyl)-5,7-dihydroxybenzopyran-4-one, or 3',4',5,7-tetrahydroxy isoflavones),

santalin (7-methoxy-5,3′,4′-trihydroxyisoflavone),

Trifolium (5,7-dihydroxy-3-(3-hydroxy-4-methoxyphenyl)benzopyran-4-one, or 4'-methoxy-3',5, 7-trihydroxyisoflavone),

Formononetin (7-hydroxy-3-(4-methoxyphenyl)chromen-4-one, or 7-hydroxy-4'-methoxyisoflavone),

• And glucosides, beta-glucosides and their alkoxy substituted derivatives and combinations thereof.

In some embodiments, the isoflavones may include at least one of the group consisting of genistein and daidzein. In some embodiments, the isoflavones may comprise a mixture of two or more isoflavones.

In some embodiments, the isoflavones may comprise genistein. Genistein is of particular interest as a hydroxyisoflavone. It has a molecular weight of 270 g/mol and melts at 306°C, it can reduce oxidative stress and reduce the concentration of pro-inflammatory cytokines without toxicity or activation of the platelet adhesion process.

The stilbenes used in the present application may include aglycones, for example, piceatannol, pinosylvin, pterostilbene, resveratrol, gnetol, oxidized resveratrol (oxyresveratrol); and glycosides, eg, picetanol glucoside (astringin) and piceid (piceid). Stilbenes are hydroxylated derivatives of stilbene. They have a C ₆ -C ₂ -C ₆ structure. Biochemically, they belong to the phenylpropanoid family.

Polymer films prepared according to the methods of the present disclosure can provide uniform/uniform distribution of stilbenes, isoflavones, or flavones on the major surface (in some embodiments, the entire major surface) of the polymer film, even at lower loadings. The same is true at low levels (up to 10% by weight). Thus, the polymer films of the present disclosure can provide high surface concentrations and bulk densities of stilbenes, isoflavones, or flavones on the major surfaces of the polymer films compared to polymer films made from mixtures of polymers and flavones, This is true even at low loading concentrations.

Polymer membranes of the present disclosure using stilbenes or flavonoids (such as genistein) as active coatings can reduce dialysis-induced oxidative stress (DIOS) and membrane-induced Inflammation (MII). Cytokines are a family of proteins involved in many immune functions, including the production and control of other cytokines. They play an important role in regulating hematopoiesis, mediating the differentiation and proliferation of different cell types. For example, it has been determined that endotoxins from dialysate, such as bacterial components, induce neutrophils to secrete IL-1β, which causes fever and hypotension during hemodialysis. IL-1β and TNF-α are known to have autocrine (ie induce/regulate their own secretion) and paracrine signaling (induce/regulate secretion of other cytokines) functions. Clinically, it has been demonstrated that serum concentrations of IL-1β and TNF-α increase several-fold during hemodialysis in a membrane-selective manner. Although cytokine secretion can be induced by polymeric membrane surfaces due to direct contact of PBMCs with the membrane and endotoxins from the dialysate, complement-mediated cytokine secretion has been generally accepted as a common mechanism by which hemodialysis membranes induce inflammation. In the case of hemodialysis, an alternative pathway of complement activation leads to the formation of complement fragments such as C3b, which coat membrane surfaces by adsorption to them. C3b molecules, along with other soluble complement fragments such as C3a and C5a, subsequently stimulate PBMCs, triggering enhanced secretion of pro-inflammatory cytokines. DIOS is activated when excessive production of oxygen free radicals overwhelms the body's natural antioxidant defense mechanisms. MII induces unwanted immune responses induced by higher concentrations of proinflammatory cytokines such as interleukin-1β (IL-1β), interleukin (IL-6) and tumor necrosis factor-R (TNF-R) in the blood. Bioincompatibility of polymer membranes is considered to be a major source of excess reactive oxygen species (ROS) generation during hemodialysis, which contributes to DIOS.

Patients on maintenance hemodialysis suffer from increased oxidative stress that promotes atherosclerosis, a major cause of excess mortality in this patient population. The excess oxygen attacks LDL, which leads to the formation of plaque in the arteries, which can lead to a heart attack. Dialysis membranes can induce free oxidative radicals when in contact with the patient's blood, which further exacerbates oxidative stress. The flavone-coated polymer membranes of the present disclosure can reduce oxidative stress generated by dialysis membranes, which can be measured by different parameters in blood, such as superoxide generation and oxidative burst.

Antioxidant properties of polymer films coated with stilbenes or flavonoids are understood by considering the mechanism of oxygen radical formation. Following cellular activation, membrane-bound nicotinamide adenine dinucleotide phosphate (NADPH) and the cytosolic component of the enzyme assemble in the membrane and form the active enzyme. NADPH oxidase catalyzes the reduction of O ₂ to superoxide anion (O ₂ ^·- ), which is then rapidly disproportionated to hydrogen peroxide (H ₂ O ₂ ). This chain of events is known as the electron transport chain. Subsequently, H ₂ O ₂ can be converted to highly reactive compounds such as hypochlorous acid (HOCl) by the enzyme myeloperoxidase. Thus, a functionally intact NADPH oxidase may be critical for neutrophils to undergo an oxidative burst. In this case, genistein successfully inhibited the expression of NADPH, the first step _in the electron transport chain to form superoxide anion and subsequent disproportionation to _H2O2 .

The polymer membranes of the present disclosure have been found to reduce serum levels of certain cytokines and promote the reduction of reactive oxygen species (ROS), which are known to play important roles in mutagenesis, carcinogenesis, and especially tumor promotion. Genistein inhibits the priming events necessary for high-level ROS production. In some embodiments, polymer films of the present disclosure can reduce oxidative outburst (i.e., ROS generation) by more than 50%, by more than 60%, or by more than 70% compared to films without a flavonoid coating, as demonstrated by Examples Measured by the method described in. In some embodiments, polymer membranes _of the present disclosure can reduce _H2O2 by greater than 20%, or greater than 25%, greater than 30%, greater than 35%, greater than 40%, Greater than 45%, or greater than 50%, as measured by the method described in the Examples.

The polymer membranes of the present disclosure have been found to be effective in retaining blood cells, such as white blood cells, red blood cells, platelets, etc., which are important for blood function. In some embodiments, polymeric membranes of the present disclosure can retain greater than 90%, 95%, 98%, 99%, or 100% of white blood cells or red blood cells as measured by the methods described in the Examples. In some embodiments, polymeric films of the present disclosure can retain greater than 70%, 75%, 80%, 85%, or 90% platelets as measured by the methods described in the Examples. In some embodiments, polymeric membranes of the present disclosure can increase platelet retention by more than 50%, 60%, 70%, 80%, 90%, or 100% compared to membranes without a flavone coating.

The polymer membranes of the present disclosure can reduce the concentration of thrombin-antithrombin complex (TAT) to reduce the effect of dialysis membranes on the coagulation system and cell activation without toxicity or activation of the platelet adhesion process. The thrombin-antithrombin complex (TAT) is significantly increased during coagulation, which can lead to activation of platelets. In some embodiments, polymer membranes of the present disclosure can reduce TAT levels in plasma by more than 10%, 20%, or 30% compared to membranes without flavone coating.

The polymer membranes of the present disclosure may be suitable for applications in the field of filtration. Due to the unique combination of properties of a polymer membrane as described herein (preferably obtained from a method as described herein), the present disclosure also provides a membrane as described herein for use in filtering liquids, such as microfiltration or ultrafiltration the use of. "Microfiltration" and "ultrafiltration" have their usual meanings in the art. Preferably, the use as described herein involves clarification and/or purification of liquid media, especially aqueous liquids. The polymer membranes of the present disclosure are useful in a variety of extracorporeal blood purification procedures, including dialysis.

The following working examples are intended to illustrate the present disclosure and not to limit it.

Example

Objects and advantages of this invention are further illustrated by the following examples, but the particular materials and amounts thereof recited in these examples, as well as other conditions and details, should not be construed to unduly limit this invention.

Materials and Test Methods

Genistein was obtained from Herb-key (China ShanxiNHK Technology, Shaanxi, China). Resveratrol (Product No. R5010) was obtained from Sigma-Aldrich, St. Louis, MO. Aldrich Company, St. Louis, MO).

White blood cell counts (WBC), red blood cell counts (RBC) and platelet counts (PC) were determined using an ABX Pentra 60 cell counter (Axon Lab AG, Reichenbach, Germany).

Total lipid peroxide content in plasma samples was determined using a chromogenic assay kit (from Immundiagnostik AG, Bensheim Germany) according to the manufacturer's instructions.

Complement component 5a (C5a) content in plasma samples was determined using an ELISA assay kit (from DRG Instrument GmbH, Marburg, Germany) according to the manufacturer's instructions.

Thrombin-antithrombin complex (TAT) content in plasma samples was determined using an ELISA assay kit (from Siemens Healthcare Diagnostics, Marburg, Germany) according to the manufacturer's instructions.

Oxidative burst activity of blood samples was determined by flow cytometry using a FACSVERSE flow cytometer (Becton Dickinson GmbH, Heidelberg, Germany). Blood samples were incubated with dihydrorhodamine 123 (DHR123) non-fluorescent dye for 10 minutes at 37°C (DHR123 is taken up by neutrophils in the sample). Next, blood cells were stimulated with and without formyl-peptide (N-formyl Nle-Leu-Phe-Nle-Try-Lys) for 15 minutes at 37°C, and then lysed with BD PHARM LYSE solution (Becton Dickinson GmbH)) lysed red blood cells. When reactive oxygen species are generated, DHR is oxidized to the fluorescent dye rhodamine. In this assay, oxidative burst activity is proportional to the intracellular fluorescence intensity of rhodamine (relative fluorescence units (RFU)) measured by flow cytometry. In each sample, 5,000 neutrophils were acquired in a forward scatter (FSC) vs. side scatter (SSC) gate. FSC and SSC were analyzed on a linear scale, and fluorescence data were analyzed on a bi-exponential scale. Data collection and analysis were performed using FACSUITE software (version 1.05, Bidi Co., Ltd.). Blood samples sensitized with formyl-peptide stimulated lipopolysaccharide (100 ng/mL, R 595 from S. minnesota) served as positive controls. Oxidative burst activity was expressed as the geometric mean of the fluorescence intensity (RFU) of rhodamine and was calculated from the difference of the geometric mean of samples incubated with and without formyl-peptide.

Hemolysis was measured by spectrophotometry (UV1650PC spectrophotometer, Shimadzu Deutschland GmbH, Duisburg, Germany) at three wavelengths (OD _380nm , OD _415nm , OD _450nm ) according to Herboe, M, Background on reference correction, Scandinavian Journal of Clinical and Lab Investigation, 1959, 11, pp. 66-70. Use Equation A to calculate plasma free hemoglobin [fHb] (g/dL). To reflect hemolysis, fHb at the end of the experiment was set relative to total hemoglobin at baseline.

Formula A:

fHb=[(168*A415nm)-(84*A380nm)-(84*A450nm)]*(DF/11); where "DF" is the plasma dilution factor

Example 1. Preparation of a dialyzer module containing a membrane coated with genistein

A coating solution of genistein in ethanol (0.4% by weight) was prepared and added to a 5 L pressurizable container. A PUREMA polyethersulfone, hollow fiber, H-type capillary membrane (200 micron inner diameter, 30 micron wall thickness, 1.1 ^m active surface area, available from 3M Company, St. Paul, MN) was inserted in the dialyzer module. The dialyzer module is tubular with open connector elements at each end of the tubing. Close the two side ports near the upper and lower ends of the module with clamps. The dialyzer module is installed in a vertical orientation, with the lower connector of the module connected to the valve port of the pressurizable container using PTFE (polytetrafluoroethylene) tubing. The vessel was pressurized (0.4 bar) and the valve was opened to allow the coating solution to flow into the lumen portion of the membrane. When the lumen is partially filled and paint solution begins to exit from the open upper connector, the valve is closed. The coating solution was maintained in the dialyzer module for 10 minutes, then the tubing was removed from the lower connector to allow the coating solution to drain from the dialyzer module. During this process, the coating solution was observed to permeate the capillary membrane wall, filling part of the extracapillary volume. After the coating solution was drained, a nitrogen source was connected at the lower connector and a gentle stream of nitrogen was passed through the membrane to evaporate residual ethanol.

Comparative Example A. Preparation of Dialyzer Modules Containing Membranes Not Coated with Genistein

The same procedure described in Example 1 was followed except that different coating solutions were used. The coating solution was ethanol without other additives.

Example 2. Analysis of human blood

Dialyzer modules prepared according to Example 1 and Comparative Example A were analyzed using freshly donated human blood samples (pooled from 2 to 3 donors). The same heparinized blood pool (3.5 IU/mL standard heparin, #H3149, Sigma-Aldrich, Steinheim, Germany) was used as the blood source for all experiments. The two side ports of each module are closed with clamps. Each dialyzer module was installed in a vertical orientation, and saline solution (1 L, 0.9% NaCl concentration) was recirculated through the module at 250 mL/min for 30 minutes. The brine flows through the module in the direction from the lower connector to the upper connector. Next, a second liter of NaCl solution (0.9%) was pumped through the module in a single pass (60 mL/min), with the liquid flowing in the direction from the lower connector to the upper connector and exiting the module through the upper connector. An aliquot (240 mL) from the heparinized blood pool was then recirculated through the module at 250 mL/min for 180 minutes. The blood was kept at 37 °C during the recirculation step, and the blood flow through the module was in the same direction as the previous saline recirculation step. Blood samples were collected before (t=0) and after (t=180) the recirculation step and subsequently analyzed. The results are reported in Table 1. For WBC, RBC, and PC, counts obtained after the recirculation step (at t=180) were compared to corresponding baseline counts obtained before the recirculation step (at t=0) and reported as a percentage relative to baseline. TAT, C5a, total lipid peroxides and oxidative burst activity were measured using blood samples obtained after the recirculation step (t=180).

For the modules of Example 1, results are reported from a single experiment. For the modules of Comparative Example A, results are reported as the mean (with standard deviation) from experiments with three individual modules (n=3). A separate aliquot of heparinized blood from the blood pool was used with each test module.

Table 1. Analysis of human blood using the protocol of Example 2

Example 3 .

A piece of 3M MICROPES Type 1F PH polyethersulfone membrane (110 microns thick from 3M Company) was immersed in an ethanol solution of resveratrol (0.8% by weight) for 5 minutes at room temperature. The membrane was removed from the solution and dried overnight at room temperature.

Comparative example B.

A piece of 3M MICROPES Type 1F PH polyethersulfone membrane (110 microns thick) was immersed in ethanol for 5 minutes at room temperature. The membrane was removed from the solution and dried overnight at room temperature.

Example 4 .

Samples (4.5 cm diameter) were punched out from films prepared according to Example 3 and Comparative Example B. Each sample was placed in a Petri dish containing 10 mL of saline solution (NaCl concentration 0.9%). The dish was shaken on an orbital shaker at 70 rpm (revolutions per minute) for 40 minutes. The saline solution was then removed from the dish, replaced with 10 mL of fresh saline solution, and the dish was shaken for 1 minute. Next, the saline solution was removed from the Petri dish and replaced with 8 mL of heparinized human blood (3.5 IU/mL standard heparin, #H3149, Sigma-Aldrich) and shaken (70 rpm) at 37°C for 3 Hour. Each blood sample was tested for total lipid peroxide and oxidative burst activity. The results are reported in Table 2 as the mean (with standard deviation) of experiments of three separate film samples (n=3).

Table 2. Analysis of human blood using the procedure of Example 4

All references and publications cited herein are expressly incorporated by reference into this disclosure in their entirety. Illustrative embodiments of this invention are discussed herein, and reference is made to variations that are possible within the scope of this invention. For example, features described in connection with one exemplary embodiment may be used in conjunction with other embodiments of the invention. These and other variations and modifications in the invention will be apparent to those skilled in the art without departing from the scope of the invention, and it should be understood that this invention is not limited to the illustrative embodiments set forth herein. Accordingly, the invention is to be limited only by the claims provided below and their equivalents.

Claims (20)

1. A film comprising: A polymer membrane made of a polymer selected from the group consisting of aromatic sulfone polymers, polyamides, cellulose, cellulose acetate, polymethylmethacrylate, polyvinyl alcohol, and polyacrylonitrile, wherein the the polymer film has a major surface; and Stilbenes, isoflavones or flavones coated on said major surface of said polymer film. 2. The polymer film of claim 1, wherein the stilbenes, isoflavones or flavones cover greater than 75% of the major surface of the polymer film. 3. The polymer film of claims 1 to 2, wherein the stilbenes, isoflavones or flavones cover greater than 80% of the major surface of the polymer film. 4. The polymeric membrane according to claims 1 to 3, wherein the polymeric membrane is a hollow fiber membrane comprising an inner surface facing its lumen, an outer surface facing outward, and a hollow fiber membrane having a wall thickness an intermediate wall, and wherein said major surface is said inner surface. 5. The polymeric film of claim 4, wherein the intermediate wall includes a plurality of pores, and the stilbenes, isoflavones, or flavones coat the surfaces of at least some of the pores. 6. The polymer membrane of claims 1 to 5, wherein the aromatic sulfone polymer comprises polyethersulfone. 7. The polymer film of claims 1 to 6, wherein the isoflavones comprise hydroxyisoflavones. 8. The polymer film according to claims 1 to 7, wherein the isoflavones are selected from the group consisting of genistein, daidzein, glycitein, puraxanthin, chicitein A, olopol, sandalwood A group consisting of flavin, red cloverin, formononetin and glucoside, 13-glucoside and its alkoxy-substituted derivatives and combinations thereof. 9. The polymer film of claims 1 to 7, wherein the isoflavones are selected from the group consisting of genistein, daidzein, and combinations thereof. 10. A method, said method comprising: forming a polymer membrane from an aromatic sulfone polymer; and Coating stilbenes, isoflavones or flavones to hollow fiber membranes. 11. The method of claim 10, wherein the coating step comprises dissolving the stilbenes, isoflavones or flavones in a solvent to form a coating solution. 12. The method of claim 11, wherein the solvent is selected from the group consisting of ethanol and isopropanol. 13. The method of claims 10-12, wherein the step of coating comprises impregnating the polymer film with the coating solution. 14. The method of claims 10-13, further comprising draining the coating solution from the polymer film after impregnating the polymer film with the coating solution. 15. The method of claims 10-14, further comprising drying the polymer film after discharging. 16. The method of claims 10-15, wherein the isoflavones are selected from the group consisting of genistein, daidzein, and combinations thereof. 17. The method of claims 10-16, wherein the polymeric membrane is a hollow fiber membrane having a lumen. 18. The method of claim 17, draining the coating solution comprising draining the coating solution from the hollow fiber membranes after the lumens of the hollow fiber membranes are filled with the coating solution. 19. The method of claims 17-18, wherein the step of coating comprises flowing the coating solution into the lumen of the polymer film. 20. Use of a polymer membrane according to claims 1 to 9 for filtering liquids.