The present invention relates to the use of additives in processes to form polymeric fibers. These fibers can be formed into membranes with improved middle and/or higher molecular weight solute removal.
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0. 32. A dialysis membrane prepared from a solution comprising:
10 to 30 wt. % of at least one polyarylether polymer,
1 to 10 wt. % of at least one hydrophilic polymer that is other than a polyvinylpyrrolidone having a k value of from 40 to 55,
and at least one solvent, wherein the dialysis membrane has:
a molecular weight cut off of 60 kda to about 65 kda such that a molecule or protein having about the size of albumin has a sieving coefficient of about 10% or less according to DIN 58352.
12. A polyarylether polymer fiber comprising at least one polyarylether polymer and at least one polyvinylpyrrolidone (PVP), wherein said at least one PVP consisting consists of at least one medium molecular weight PVP having a k value of from 45 to 53 and present in an amount of from 0.1 wt % to 8 wt % based on weight of said polyarylether polymer fiber, wherein a membrane formed from a plurality of the polyarylether polymer fibers has an ultrafiltration constant (kUF) of from about 100 ml/hr*mmHg*m2 to about 600 ml/hr*mmHg*m2, and has an albumin sieving coefficient of from about 0.001% to about 0.5%.
21. A dialysis membrane comprising a plurality of polyarylether polymer fibers, said polyarylether polymer fibers comprising at least one polyarylether polymer and at least one polyvinylpyrrolidone (PVP), wherein said at least one PVP consisting of at least one medium molecular weight PVP having a k value of from 45 to 53 and present in an amount of from 0.1 wt % to 8 wt % based on weight of said polyarylether polymer fibers, wherein the dialysis membrane has an ultrafiltration constant (kUF) of from about 100 ml/hr*mmHg*m2 to about 600 ml/hr*mmHg*m2, and has an albumin sieving coefficient of from about 0.001% to about 0.5%.
0. 31. A polyarylether polymer fiber formed from a solution comprising at least one polyarylether polymer, at least one polyvinylpyrrolidone (PVP), and a solvent, wherein said at least one PVP has a k value that is below 40 or above 55 or both;
wherein said polyarylether polymer fiber has a high sieving coefficient for molecules of molecular weight of about 65 kda or less while maintaining a sieving coefficient of 1% or less for proteins with molecular weights greater than about 65 kda, and
wherein said high sieving coefficient includes a sieving coefficient of 1.0 for Vitamin B12, about 0.99 for inulin, and from about 0.9 to about 1.0 for myoglobin.
1. A method of forming a dialysis membrane comprising a plurality of polyarylether polymer fibers, wherein the polyarylether fibers are produced by a method comprising the steps of:
providing a spin mass comprising at least one polyarylether polymer and at least one organic solvent;
providing a bore fluid comprising at least one aqueous solvent and/or at least one organic solvent;
combining the spin mass and bore fluid to form the polyarylether polymer fibers;
and forming a dialysis membrane from a plurality of said polyarylether polymer fibers;
wherein the spin mass or the bore fluid or both comprises at least one additive;
wherein the spin mass comprises one medium molecular weight PVP having a k value of from k41 to K54 in an amount of from 0.1 wt % to 8 wt % and 0 wt % low molecular weight (MW) PVP and 0 wt % high molecular weight PVP by weight of the spin mass;
wherein the bore fluid comprises 0 wt % low MW PVP by weight of the bore fluid and 0 wt % high MW PVP; and
wherein the low MW PVP has a weight average molecular weight of less than about 100 kda.
2. The method of
3. The method of
4. The method of
wherein the medium MW PVP has a weight average molecular weight of from about 100 kda to 900 kda.
5. The method of
7. The method of
a) sharpen the sieving curve for improved middle molecule removal;
b) remove larger uremic solutes from fluids;
c) improve middle molecule removal without a substantial increase in albumin leakage; and
d) fully or partially replace PVP or a MW class of PVP or a similar minority polymeric component present in a spin mass, and still obtain the same or similar properties for the produced polyarylether polymer fiber.
8. The method of
10. The method of
11. The method of
13. The polyarylether polymer fiber of
14. The method of
15. The polyarylether polymer fiber of
16. The polyarylether polymer fiber of
17. The polyarylether polymer fiber of
18. The polyarylether polymer fiber of
19. The polyarylether polymer fiber of
20. The polyarylether polymer fiber of
0. 22. The method of claim 1, wherein the viscosity of the spin mass is 500 to 10,000 cps (centipoise) at about 25° C.
0. 23. The method of claim 22, wherein the viscosity of the spin mass is 1,000 to 2,500 cps (centipoise) at about 25° C.
0. 24. The dialysis membrane of claim 21, wherein the at least one hydrophilic polymer comprises less than about 10% high molecular weight PVP, less than 10% low molecular weight PVP, or both.
0. 25. The polyarylether polymer fiber of claim 31, wherein the sieving coefficient of myoglobin is from 0.9 to about 1.0.
0. 26. The dialysis membrane of claim 32, wherein the sieving coefficient of insulin is about 0.99.
0. 27. The polyarylether polymer fiber of claim 31, wherein the clearance of lysozyme is from about 75 ml/min. to about 150 ml./min.
0. 28. The dialysis membrane of claim 32, wherein the clearance of vitamin B12 is from about 150 ml/min. to about 250 ml/min.
0. 29. The polyarylether polymer fiber of claim 31, wherein the polyarylether polymer fiber exhibits a water absorption capacity of from 1% to 10%.
0. 30. The polyarylether polymer fiber of claim 31, wherein the polyarylether polymer fiber exhibits an ultrafiltration constant kUF of from about 100 ml/hr*mmHg*m2 to about 600 ml/hr*mmHg*m2.
0. 33. The dialysis membrane of claim 32, wherein the dialysis membrane further has a middle molecule (lysozyme) clearance rate of from about 50 ml/min of lysozyme to about 250 ml/min of lysozyme with Qb/Qd=300/500 ml/min.
0. 34. The dialysis membrane of claim 32, wherein the at least one hydrophilic polymer includes at least one polyvinylpyrrolidone having a k value of K80 or higher.
0. 35. The dialysis membrane of claim 32, wherein the at least one hydrophilic polymer includes at least one polyvinylpyrrolidone having a k value of K36 or lower.
0. 36. The dialysis membrane of claim 32, wherein the at least one hydrophilic polymer includes at least one polyvinylpyrrolidone having a k value of from K80 to K105.
0. 37. The dialysis membrane of claim 32, wherein the at least one hydrophilic polymer includes at least one polyvinylpyrrolidone having a k value of from K1 to K36.
0. 38. The polyarylether polymer fiber of claim 31, wherein the at least one PVP is at least one polyvinylpyrrolidone having a k value of K80 or higher.
0. 39. The polyarylether polymer fiber of claim 31, wherein the at least one PVP is at least one polyvinylpyrrolidone having a k value of K36 or lower.
0. 40. The polyarylether polymer fiber of claim 31, wherein the at least one PVP is at least one polyvinylpyrrolidone having a k value of from K80 to K105.
0. 41. The polyarylether polymer fiber of claim 31, wherein the at least one PVP is at least one polyvinylpyrrolidone having a k value of K1 to K36.
0. 42. The polyarylether polymer fiber of claim 31, wherein the at least one PVP is at least one polyvinylpyrrolidone having a k value of K36 or lower and at least one polyvinylpyrrolidone having a k value of K80 or higher.
0. 43. The dialysis membrane of claim 32, wherein the at least one hydrophilic polymer is at least one polyvinylpyrrolidone having a k value of K36 or lower and at least one polyvinylpyrrolidone having a k value of K80 or higher.
0. 44. The polyarylether polymer fiber of claim 31, wherein the at least one PVP comprises at least one polyvinylpyrrolidone having a k value of K36 or lower in an amount of from 4 wt % to 10 wt % based on said solution.
0. 45. The dialysis membrane of claim 32, wherein said at least one hydrophilic polymer is at least one polyvinylpyrrolidone having a k value of K36 or lower in an amount of from 4 wt % to 10 wt % based on said solution.
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This application
While the above is considered to be more accurate with regards to determining K value, some literature provides that the weight average molecular weight of the polyvinylpyrrolidone can be determined by a K value using the following equation, also illustrated graphically in FIG. 15 of the BASF Technical Information literature entitled “Kollidon: Polyvinylpyrrolidone for the Pharmaceutical Industry,” wherein MW is the weight average molecular weight, K is the K value, and a is exp (1.055495):
MW=a*K2.97159
More specific examples of the ability to control and/or reduce the presence of PVP in methods to make polymeric fibers are provided below. Examples of low MW PVP include, but are not limited to, at least one of PVP K12, PVP K30, or any PVP with a K value (or K value range) of from 1 to 36, or any combinations thereof. As an option, the spin mass and/or the bore fluid includes no low MW PVP. As an option, with the present invention, the spin mass and/or the bore fluid can contain a single weight average MW species (weight average of species) of PVP (e.g., a single PVP K value or single PVP K grade). As an option, the spin mass and/or the bore fluid contains a medium MW PVP. The spin mass can contain less than 25 wt % medium MW PVP by weight of the total PVP present in the spin mass (e.g., 0.001 wt % to 24 wt %, 1 wt % to 10 wt %, 1 wt % to 5 wt %, 0.01 wt % to 3 wt %, 0.01 wt % to 1 wt %). The bore fluid can contain less than 25 wt % medium MW PVP by weight of the bore fluid (e.g., 0.001 wt % to 24 wt %, 1 wt % to 10 wt %, 1 wt % to 5 wt %, 0.01 wt % to 3 wt %, 0.01 wt % to 1 wt %). The medium MW PVP can have a weight average molecular weight of from 100 kDa to less than 900 kDa, such about 100 kDa to 850 kDa (or a K value of K37 to K79). As an option, the spin mass (that is, the total PVP 30 content in the spin mass based on the total weight percent of PVP), the bore fluid, or both can have less than about 90 wt %, less than about 75 wt %, less than about 50 wt %, less than about 25 wt %, less than about 15 wt %, less than about 7.5 wt %, less than about 5 wt %, less than about 2.5 wt %, less than about 1 wt %, less than 0.1 wt %, or less than about 0.001 wt % medium MW PVP, by weight of the spin mass (based on the total weight percent of PVP present in the spin mass) and/or bore fluid. For these ranges, a lower limit can be 0.0001 wt %. The medium MW PVP can be or include PVP having a K value or K value range of from K37 to 79, such as from K40 to K75, K45 to K70, K45 to K65, K45 to K60, K45 to K55 or any individual K value in these ranges. K values of K45 to K55 are especially effective in the present invention. As an option, the spin mass and/or the bore fluid can contain a high MW PVP; wherein the spin mass (based on the total weight of the spin mass or based on the total weight percent of PVP present in the spin mass) contains less than 25 wt % high MW PVP by weight of the spin mass; and/or wherein the bore fluid contains less than 25 wt % high MW PVP by weight of the bore fluid; and wherein the high MW PVP has a weight average molecular weight of equal to or greater than 900 kDa (or a K value of K80 or higher). As an option, the spin mass (based on the total weight of the spin mass or based on the total weight percent of PVP present in the spin mass), the bore fluid, or both has less than about 90 wt %, less than about 75 wt %, less than about 50 wt %, less than about 25 wt %, less than about 15 wt %, less than about 7.5 wt %, less than about 5 wt %, less than about 2.5 wt %, less than about 1 wt %, less than 0.1 wt %, or less than about 0.001 wt % high MW PVP. For these ranges, a lower limit can be 0.0001 wt %. The high MW PVP can have a K value or K value range of from K80 to K105 or higher, such as from K80 to K90, K81 to K88 or K81 to K86 or any individual K value in these ranges. The high MW PVP used in the examples had a weight average MW˜900,000 Da.
As one example, the spin mass formulation can contain less than 25 wt % high molecular weight PVP by weight of the total PVP content in the spin mass. More specific examples of these amounts can be of the ranges set forth immediately above this paragraph. The spin mass (by weight of the spin mass or by weight of the total PVP content) and/or bore fluid can have less than about 10 wt % high molecular weight PVP, such as less than 0.001 wt % high molecular weight PVP or 0 wt % high molecular weight PVP. As an option, the spin mass, with regard to PVP components, can contain some or exclusively a medium molecular weight PVP, such as a PVP having an average molecular weight of from about 50,000 Da to about 310,000 Da, for instance, from about 200,000 Da to 300,000 Da, or from about 215,000 Da to about 285,000 Da, and the like. The medium molecular weight PVP can be a PVP having a K value of from K37 to K79, such as from K40 to K75, K45 to K70, K45 to K65, K40 to K55, K45 to K60, K45 to K55 or any individual K value in these ranges and can be or include PVP K40, K41, K42, K43, K44, K45, K46, K47, K48, K49, K50, K51, K52, K53, K54, and/or K55. It has been found that the use of a medium molecular weight PVP (or more than one type of medium MW PVP) can replace partially or entirely a high molecular weight PVP component and/or replace partially or entirely a low molecular weight PVP component, and yet achieve comparable, if not better, performance properties with regard to the fiber and, in the present invention, this can be achieved with a water content of 4 wt % or less in the spin mass. The PVP component can be a medium molecular weight PVP that comprises 100 wt %, 10 wt % to 100 wt %, 20 wt % to 100 wt %, 30 wt % to 100 wt %, 40 wt % to 100 wt %, 50 wt % to 100 wt %, 60 wt % to 100 wt %, 75 wt % or more, 85 wt % or more of all PVP containing components in the bore fluid and/or spin mass or both (based on the total PVP content in the spin mass). Unless stated otherwise, the reference to molecular weight is a reference to weight average molecular weight throughout the present application.
The present invention also relates to a polyarylether polymer fiber comprising at least one polyarylether polymer and at least one polyvinylpyrrolidone (PVP), wherein said at least one PVP comprising at least one medium weight PVP having a K value of from 40 to 55 or 45 to 55. The polyarylether polymer fiber can have a medium molecular weight PVP with a K value of from 47 to 53. The medium molecular weight PVP can be present in an amount of from about 0.1 wt % to 15 wt %, based on the weight of the polyarylether polymer fiber, such as from about 1 wt % to 10 wt %, based on the weight of the polyarylether polymer fiber, or from about 3 wt % to 8 wt %, based on the weight of the polyarylether polymer fiber. The polyarylether polymer fiber can be a sulfone polymer fiber. The polyarylether polymer fiber can be a polysulfone fiber. The PVP present in the fiber can be considered dispersed or distributed in the polyarylether polymer, either in a uniform or non-uniform manner. The PVP can be dispersed or distributed such that the PVP concentration is higher on the outer surface area of the fiber (e.g., the weight concentration of PVP can be 1% to 100% higher in the outer surface area of the fiber).
The polyarylether polymer fiber can further comprise 0 wt % to 15 wt % of at least one low molecular weight PVP having a K value of 36 or less or a K value of 30 or less, such as 0 wt % to 10 wt %, or 0 to 5 wt %, from 0 wt % to 0.3 wt %, from 0 wt % to 0.2 wt %, from 0 wt % to 0.1 wt %, or from 0 wt % to 1 wt %. With the polyarylether polymer fiber of the present invention, the PVP can further comprise 0 wt % of any low molecular weight PVP having a K value of 36 or less, such as 30 or less.
The polyarylether polymer fiber of the present invention can further comprise from 0 wt % to 15 wt % of at least one high molecular weight PVP having a K value of 80 or higher, such as 0 wt % to 10 wt % of at least one high molecular weight PVP having a K value of 80 or higher, or from 0 wt % to 0.3 wt %, from 0 wt % to 0.2 wt %, from 0 wt % to 0.1 wt %, 0 wt % to 5 wt % of at least one high molecular weight PVP having a K value of 80 or higher, or 0 wt % to 1 wt % of at least one high molecular weight PVP having a K value of 80 or higher, or 0 wt % of any high molecular weight PVP having a K value of 80 or higher.
The polyarylether polymer fiber of the present invention can be in the absence of a PVP with a K value of 44 or less, 42 or less, 40 or less, 39 or less, or 30 or less (e.g., K1 to K40).
The polyarylether polymer fiber of the present invention can be in the absence of a PVP with a K value of 56 or higher, or 60 or higher, or 70 or higher, or 80 or higher, or 90 or higher (e.g., K56 to K120).
The polyarylether polymer fiber of the present invention can have one or more of the following properties:
Another feature of the present invention is a polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) produced by a method of the present invention or any other suitable method. The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) produced can have a zeta (streaming) potential of from about −500 mV to about 500 mV, from about −250 mV to about 250 mV, from about −100 mV to about 100 mV, from about −25 mV to about 25 mV, or from about −10 mV to about 10 mV. The water permeability of membranes formed from the fibers can be evaluated by determining the ultrafiltration coefficient (KUF). The KUF is defined as the number of milliliters of fluid per hour that will be transferred across the membrane per mm Hg pressure gradient across the membrane. Hollow fiber membranes produced can have a water permeability (KUF per area), for example, of from about 1 to about 1000 ml/hr·mm Hg·m2 or higher, from about 10 to about 50 ml/hr·mm Hg·m2, from about 25 to about 1000 ml/hr·mm Hg·m2′ from about 30 to about 900 ml/hr·mm Hg·m2, from about 100 to about 600 ml/hr·mm Hg·m2, or from about 150 to about 250 ml/hr·mm Hg·m2, greater than about 750 ml/hr·mm Hg·m2, or other values.
The hollow fibers of the present invention can have a water absorption capacity, for example, of from about 1% to about 10% by weight, or from about 2% to about 9% by weight, or from about 3% to about 8% by weight, or other values. The water absorption capacity can be ascertained in the following manner. Water-vapor saturated air is passed at room temperature (25° C.) through a dialyzer fitted with the hollow fibers and in a dry condition. In this respect, air is introduced under pressure into a water bath and after saturation with water vapor is run into the dialyzer. As soon as a steady state has been reached, it is then possible for the water absorption capacity to be measured.
The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) of the present invention can be designed with a variety of sieving/clearance properties. Clearance data can be measured on hollow fibers of the present invention, for example, according to DIN 58,352. The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) can have an albumin sieving coefficient of less than about 20%, from about 0.001% to about 1%, from about 0.01% to about 0.75%, from about 0.1% to about 0.5%, from about 0.05% to about 10%, or more than 0.5%. For example, the maximum blood flow for a patient can be from about 450 ml/min to about 500 ml/min. The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) can have an albumin sieving coefficient less than about 20% and clearance rate less than 100% of the blood side flow rate. The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) into a dialyzer, for example, of about 1.4 m2 area, can have a vitamin B12 clearance rate of from about 1 ml/min of vitamin B12 to about 300 ml/min of vitamin B12, from about 10 ml/min of vitamin B12 to about 300 ml/min of vitamin B12, from about 150 ml/min of vitamin B12 to about 250 ml/min of vitamin B12, or from about 75 ml/min of vitamin B12 to about 150 ml/min of vitamin B12 (e.g., each at Qb/Qd=300/500 ml/min). The vitamin B12 clearance rate can be about 250 ml/min at Qb/Qd=300/500 ml/min. The polysulfone-based fiber fabricated into a dialyzer, for example, of about 1.4 m2 area, can have a middle molecule (lysozyme) clearance rate of from about 1 ml/min of lysozyme to about 300 ml/min of lysozyme, from about 10 ml/min of lysozyme to about 300 ml/min of lysozyme, from about 50 ml/min of lysozyme to about 250 ml/min of lysozyme, or from about 75 ml/min of lysozyme to about 150 ml/min of lysozyme. The lysozyme clearance rate can be about 92 ml/min. Any of the clearance rates can be stated in respect to Qb/Qd=300/500 ml/min.
The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) fabricated into a dialyzer, for example, of about 1.4 m2 area, can have a creatinine clearance rate of from about 1 ml/min of creatinine to about 300 ml/min of creatinine, from about 10 ml/min creatinine to about 300 ml/min of creatinine, from about 50 ml/min of creatinine to about 290 ml/min of creatinine, or from about 75 ml/min of creatinine to about 150 ml/min of creatinine. The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) fabricated into a dialyzer, for example, of about 1.4 m2 area, can have a beta-2-microglobulin clearance rate of from about 1 ml/min of beta-2-microglobulin to about 300 ml/min of beta-2-microglobulin, from about 10 ml/min of beta-2-microglobulin to about 300 ml/min of beta-2-microglobulin, from about 20 ml/min of beta-2-microglobulin to about 200 ml/min of beta-2-microglobulin, or from about 30 ml/min of beta-2-microglobulin to about 150 ml/min of beta-2-microglobulin. Any of the clearance rates can be stated in respect to Qb/Qd=300/500 ml/min.
Sodium clearance can be ascertained with aqueous solutions for hollow fibers having 1.25 square meters of active surface area according to DIN 58,352 at a blood flow rate of about 280 mL/min. The clearance is equal to or lower than the blood flow or inlet flow. The sodium clearance of hollow fibers of the present invention can be, for example, from about 200 to about 300, or from about 250 to about 275, or from about 260 to about 280, or from about 265 to about 275, or other values. The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) can have a sodium clearance rate of from about 1 ml/min of sodium to about 300 ml/min of sodium, from about 10 ml/min of sodium to about 300 ml/min of sodium, from about 50 ml/min of sodium to about 290 ml/min of sodium, or from about 75 ml/min of sodium to about 295 ml/min of sodium. Any of the clearance rates can be stated in respect to Qb/Qd=300/500 ml/min. For example, a sodium clearance rate can be from about 30 ml/min of sodium to about 300 ml/min of sodium with Qb/Qd=300/500 ml/min.
The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) can have any fiber geometry. For instance, the fiber can have an outside diameter of from about 1 μm to about 1 mm, from about 5 μm to about 500 μm, from about 25 μm to about 250 μm, from about 15 μm to about 150 μm, or from about 50 μm to about 100 μm. For example, the outside diameter can be about 420 μm. The interior diameter can be from about 10 μm to about 1 mm, from about 25 μm to less than 500 μm, from about 50 μm to about 250 μm, from about 15 μm to about 150 μm, or from about 50 μm to about 100 μm. The wall thickness can be about from about 0.001 μm to less than 250 μm, from about 0.01 μm to about 100 μm, from about 0.1 μm to about 50 μm, from about 1 μm to about 25 μm, or from about 10 μm to about 20 μm. The fiber length can be from about 0.01 m to about 1 m, such as from about 25 cm to about 60 cm. The polyarylether polymer fiber (e.g., a sulfone polymer fiber like a polysulfone fiber) can have a tensile strength of from about 0.1 to about 10 MPa, from about 0.1 to about 5 MPa, from about 1 to about 5 MPa, from about 2 to about 8 MPa or more. Alternatively, tensile strength can be measured in g(force). For example, a fiber can withstand a g(force) of from about 1 g(force) to about 50 g(force), from about 5 g(force) about 40 g(force), from about 10 g(force) to about 30 g(force), less than about 2 g(force), or greater than about 50 g(force). For example, a fiber withstanding from about 18 g(force) to about 30 g(force), can have a wall thickness of about 15 μm or greater, an outside diameter of about 215 μm, and an interior diameter of about 185 μm. The interior diameter can be about 140 μm or higher for a fiber having an outer diameter of about 170 μm.
Membranes made from fibers of the present invention can have an excellent separation boundary. The sieving coefficients, for example, can be measured as 1.0 for Vitamin B12, about 0.99 for inulin, from about 0.9 to about 1.0 for myoglobin, and under 0.01 for human albumin, or other values. The outer diameter of the hollow fibers, for example, can equal to about 0.1 to about 0.4 mm, whereas the thickness of the membrane can be about 10 to about 100 μm or from about 15 to about 50 μm. The hollow fibers produced with the present invention can approximate, at least in part, natural kidney function with respect to separating properties (e.g., sieving coefficient).
Membranes can be made with the fibers of the present invention. The membranes can be, for example, flat sheet or hollow fiber. The membranes can be used, for example, for dialysis membranes, ultrafiltration membranes, or microfiltration membranes. The dialysis membranes can be, for example, hemodialysis membranes. Semi-permeable membrane filtration can be used in the purification of proteins, including microfiltration and ultrafiltration. Microfiltration can be defined as a low pressure membrane filtration process which removes suspended solids and colloids generally larger than about 0.1 μm in diameter. Such processes can be used to separate particles or microbes such as cells, macrophage, and cellular debris. Ultrafiltration membranes are characterized by pore sizes which enable them to retain macromolecules having a molecular weight ranging from about 500 to about 1,000,000 Daltons. Ultrafiltration is a low-pressure membrane filtration process that can separate solutes, in some cases, up to about 0.1 μm in size, such as in a range of from about 0.01 μm to about 0.1 μm. Ultrafiltration can be used for concentrating proteins, and removing bacteria and viruses from a solution. Ultrafiltration also can be used for purification treatments, such as water purification. Dialysis membranes can be ultrafiltration membranes that contain biocompatible materials. When the membranes are hollow fibers, the hollow fibers can be microporous and capable of withstanding from about 100 psi to about 2,000 psi or more applied pressure without collapse.
A hollow fiber of the present invention that can be used for dialysis, such as hemodialysis, can have desirable properties including, for example, one or more of biocompatibility, high hydraulic permeability, a sharp separation characteristic, a satisfactory degree of mechanical strength to resist the pressures involved, and an excellent stability.
The present invention includes the following aspects/embodiments/features in any order and/or in any combination:
1. The present invention relates to a method of spinning a polyarylether polymer fiber comprising the steps of:
providing a spin mass comprising at least one polyarylether polymer and at least one organic solvent;
providing a bore fluid comprising at least one aqueous solvent and/or at least one organic solvent;
combining the spin mass and bore fluid to form the polyarylether polymer fiber;
wherein the spin mass or the bore fluid or both comprises at least one additive;
wherein the spin mass comprises less than 4 wt % low molecular weight (MW) PVP by weight of the spin mass;
wherein the bore fluid comprises less than 1 wt % low MW PVP by weight of the bore fluid; and
wherein the low MW PVP has a weight average molecular weight of less than about 100 kDa (or a K value of K36 or less).
2. The method of any preceding or following embodiment/feature/aspect, wherein the spin mass comprises dimethylacetamide (DMAC), and the bore fluid comprises DMAC and water.
3. The method of any preceding or following embodiment/feature/aspect, wherein the at least one additive comprises at least one divalent salt, polyelectrolyte, glycerine, surfactant, vinylpyrrolidone/vinylacetate copolymer, vinylcaprolactam/vinylpyrrolidone/dimethylamino-propylmethacrylamide terpolymer, polyethylene glycol polyester copolymer, or poly(ethyleneimine)-PEI, or any combination thereof, in the spin mass.
4. The method of any preceding or following embodiment/feature/aspect, wherein the at least one additive comprises at least one polyelectrolyte in the bore fluid.
5. The method of any preceding or following embodiment/feature/aspect, wherein the spin mass comprises the at least one additive.
6. The method of any preceding or following embodiment/feature/aspect, wherein the at least one additive comprises at least one divalent salt, polyelectrolyte, glycerine, surfactant, vinylpyrrolidone/vinylacetate copolymer, vinylcaprolactam/vinylpyrrolidone/dimethylamino-propylmethacrylamide terpolymer, polyethylene glycol polyester copolymer, or poly(ethyleneimine)-PEI, or any combination thereof, in the bore fluid.
7. The method of any preceding or following embodiment/feature/aspect, wherein the bore fluid comprises the at least one additive.
8. The method of any preceding or following embodiment/feature/aspect, wherein the at least one additive comprises at least one divalent salt.
9. The method of any preceding or following embodiment/feature/aspect, wherein the low MW PVP has a K value of K35 or less.
10. The method of any preceding or following embodiment/feature/aspect, wherein the spin mass comprises no low MW PVP.
11. The method of any preceding or following embodiment/feature/aspect, wherein neither the spin mass nor bore fluid comprises a low MW PVP.
12. The method of any preceding or following embodiment/feature/aspect, wherein the spin mass comprises a single weight average MW species of PVP.
13. The method of any preceding or following embodiment/feature/aspect, wherein the spin mass comprises at least one medium MW PVP;
wherein the spin mass comprises less than 25 wt % medium MW PVP by weight of the spin mass;
wherein the bore fluid comprises less than 25 wt % medium MW PVP by weight of the bore fluid; and
wherein the medium MW PVP has a weight average molecular weight of from about 100 kDa to 900 kDa (or a K value of K37 to K79).
14. The method of any preceding or following embodiment/feature/aspect, wherein the medium MW PVP has a K value of from 40 to 53.
15. The method of any preceding or following embodiment/feature/aspect, wherein at least one of the spin mass comprises a high MW PVP;
wherein the spin mass comprises less than 25 wt % high MW PVP by weight of the spin mass;
wherein the bore fluid comprises less than 25 wt % high MW PVP by weight of the bore fluid; and
wherein the high MW PVP has a weight average molecular weight greater than 900 kDa (or a K value of K80 or higher).
16. The method of any preceding or following embodiment/feature/aspect, wherein the high MW PVP has a K value of from 80 to 100.
17. The method of any preceding or following embodiment/feature/aspect, wherein the at least one additive comprises at least one medium MW PVP.
18. The method of any preceding or following embodiment/feature/aspect, wherein the spin mass comprises from 0.1 wt % to 10 wt % of at least one medium MW PVP.
19. The method of any preceding or following embodiment/feature/aspect, wherein the bore fluid comprises 0 wt % PVP.
20. The method of any preceding or following embodiment/feature/aspect, wherein both the spin mass and the bore fluid comprise at least one additive.
21. The method of any preceding or following embodiment/feature/aspect, wherein the spin mass and the bore fluid comprise the at least one additive which is the same.
22. The method of any preceding or following embodiment/feature/aspect, wherein said at least one polyarylether polymer is at least one polysulfone.
23. The method of any preceding or following embodiment/feature/aspect, wherein said at least one polyarylether polymer is at least one sulfone polymer.
24. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has a zeta (streaming) potential of from about −100 mV to about 100 mV.
25. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has an ultrafiltration constant (KUF) of from about 100 ml/hr*mmHg*m2 to about 1000 ml/hr*mmHg*m2.
26. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has an albumin sieving coefficient of from about 0.001% to about 1%.
27. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has a vitamin B12 clearance rate of from about 150 ml/min to about 250 ml/min at Qb/Qd=300/500 ml/min.
28. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has a creatinine clearance rate of from about 50 ml/min of creatinine to about 290 ml/min of creatinine with Qb/Qd=300/500 ml/min.
29. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has a sodium clearance rate of from about 30 ml/min of sodium to about 300 ml/min of sodium with Qb/Qd=300/500 ml/min.
30. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has a beta-2-microglobulin clearance rate of from about 50 ml/min of beta-2-microglobulin to about 250 ml/min of beta-2-microglobulin with Qb/Qd=300/500 ml/min.
31. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has a middle molecule (lysozyme) clearance rate of from about 50 ml/min of lysozyme to about 250 ml/min of lysozyme with Qb/Qd=300/500 ml/min.
32. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has the following fiber geometry: an outside diameter of from about 100 μm to about 0.5 mm, an interior diameter of from about 100 μm to less than 0.5 mm, a thickness of from about 0.001 μm to about 250, and a length of from about 0.01 m to about 1 m.
33. The method of any preceding or following embodiment/feature/aspect, wherein the fiber produced has a tensile strength of from about 0.1 to about 10 MPa.
34. A polymer fiber, such as a polysulfone-based fiber, produced by the method of any preceding or following embodiment/feature/aspect.
35. A method to form polymeric fibers comprising supplying a spin mass to a spinneret simultaneously with a bore fluid and casting polymeric fibers,
wherein said spin mass comprises at least one polymer and at least one organic solvent and said bore fluid comprises at least one aqueous solvent and/or at least one organic solvent, and wherein said spin mass, bore fluid, or both further comprise at least one additive in a sufficient amount so as to achieve at least one of following properties as compared to the same polymeric fiber made in the same process, but without said additive being present:
The present invention can include any combination of these various features or embodiments above and/or below as set forth in sentences and/or paragraphs. Any combination of disclosed features herein is considered part of the present invention and no limitation is intended with respect to combinable features.
The following examples further illustrate the invention but, of course, should not be construed as in any way limiting its scope.
In accordance with the present invention, this example demonstrates the superior performance of the dialysis fiber of the present invention.
The properties of a membrane for use in dialyzers were studied from the standpoint of additions in the spin mass or in the bore fluid.
As set forth in Table 1 below, various experiments were run to determine the effects of using one or more additives in the spin mass or bore fluid. The polysulfone used was P-3500, which was a commercial product made by Solvay Specialty Polymer which has a MW in the range of about 75,000-86,000 Da. The high MW PVP was a polyvinylpyrrolidone from ISP Chemicals having a K value range of from about 81 to 86.
The polysulfone was used in each of the examples and was used in about the same amount, namely 720 g. In all but two of the examples, the high MW PVP was present in an amount of 180 g. In Fiber 1-5 and Fiber 1-6, instead of the high MW PVP, a lower molecular weight PVP additive having a K value of from about 46 to about 55 was used. In Fiber 1-5, extra water was also used in the spin mass for Fiber 1-5, whereas water was not used in the spin mass for Fiber 1-6. In each of these examples, the spin mass had from about 1.8 to 2.5 wt % water, based on total solution.
In more detail, in Fiber 1-1 and Fiber 1-2, the bore fluid was modified with an additive. In Fiber 1-1, the additive was a salt, namely calcium chloride; whereas in Fiber 1-2, the additive was a surfactant, namely Pluronic F108 surfactant.
In Fiber 1-3, the spin mass was modified with an additive, namely a salt, which was calcium chloride. In Fiber 1-4 and Fiber 1-7, the bore fluid was modified with polyelectrolyte. In Fiber 1-5 and Fiber 1-6, as indicated above, the spin mass was modified using a lower molecular weight PVP having a K value of from about 46 to about 55 and this PVP was used instead of the high MW PVP. In Fiber 1-7, the bore fluid was modified using the polyelectrolyte.
In each of the cases, the fibers were spun on a pilot line and for dialysis testing, the dialyzer was sterilized by e-beam.
With regard to the properties, the performance properties were measured according to standard testing procedures, namely DIN EN1283. The ultra-filtration coefficient (Kuf) was determined using an aqueous solution instead of blood and was 10% of blood flow.
In each of Fiber 1-1 to Fiber 1-6, the spin mass had less than 4 wt % low molecular weight PVP by weight of the spin mass, and the bore fluid had less than 1 wt % low molecular weight PVP by weight of the bore fluid. In fact, in these examples, the spin mass and the bore fluid did not contain any intentional amounts of low molecular weight PVP.
As shown in the examples, the ultra-filtration coefficient (Kuf) was determined along with the zeta potential, the albumin sieving coefficient (albumin SC), the vitamin B12 clearance rate, the sodium clearance rate, and the creatinine clearance rate.
For each of Fiber 1-1 to Fiber 1-7, the various performance properties, as set forth in Table 1, were considered acceptable. Further, as shown in Table 1, the additives had the ability to alter one or more performance properties. For instance, with regard to Fiber 1-7, the Gafquat polyelectrolyte in the bore fluid had the ability to alter significantly the zeta potential, which can be useful for purposes of changing the surface charge on the membrane. Thus, the examples confirmed that the bore fluid and/or spin mass can be successfully altered by using one or more additives in order to alter and preferably improve one or more properties, especially performance properties, of the fibers used in dialyzers.
Table 1 shows the components and properties of different dialysis fibers in accordance with the present invention.
TABLE 1
COMPONENTS AND PROPERTIES OF DIALYSIS FIBERS
Fiber
Fiber
Fiber
Fiber
Fiber
Fiber
Fiber
Component
Units
Control
1-1
1-2
1-3
1-4
1-5
1-6
1-7
P-3500
g
720
720
720
720
720
720
718.3
720
polysulfone*
High MW
g
180
180
180
180
180
0
0
180
PVP*
Additive*
None
CaCl2
PVP
PVP
K46-55
K46-55
Additive*
g
72
238
238.2
Non-
Water
Solvent*
Non-
g
84
Solvent*
DMAC*
g
3550
3550
3550
3550
3550
3550
3550
3550
Precip.
42.5%
43% +
0.1%
38%
0.1% PEI
41.5%
43%
0.05% Gafquat
Cone, water
4%
Pluronic
in 42%
440 in 42.5%
in DMAC
CaCl2
F108
(bore fluid)
in 43%
PERFORMANCE PROPERTIES
Kuf/m2
ml/hr-
200
378
166
347
135
376
460
313
mmHg-
m2
Sodium Cl.
ml/min
267
284
275
282
267
272
279
267
Creatinine
ml/min
242
259
253
259
245
NA
NA
NA
Cl.
B12 Cl.
ml/min
157
193
174
187
168
175
189
167
Plasma
%
0.05
1
0.04
0.7
0.006
~0.2
0.07
NA
Albumin
SC
Zeta
mV
−12
NA
−5
−9
+32
−18
NA
+33
Potential
*Spin mass
NA = Not Available
As can be seen in Table 1, all Fibers of the present invention provided suitable one or more suitable performance properties. Fiber 1-5 and Fiber 1-6 showed that acceptable fibers can be made with just a medium molecular weight PVP, and without low MW PVP and without high MW PVP. The medium MW PVP had the ability to eliminate the need for other MW classes of PVP and served as an additive that provided numerous benefits to the fiber and fiber properties.
Applicants specifically incorporate the entire contents of all cited references in this disclosure. Further, when an amount, concentration, or other value or parameter is given as either a range, preferred range, or a list of upper preferable values and lower preferable values, this is to be understood as specifically disclosing all ranges formed from any pair of any upper range limit or preferred value and any lower range limit or preferred value, regardless of whether ranges are separately disclosed. Where a range of numerical values is recited herein, unless otherwise stated, the range is intended to include the endpoints thereof, and all integers and fractions within the range. It is not intended that the scope of the invention be limited to the specific values recited when defining a range.
Other embodiments of the present invention will be apparent to those skilled in the art from consideration of the present specification and practice of the present invention disclosed herein. It is intended that the present specification and examples be considered as exemplary only with a true scope and spirit of the invention being indicated by the following claims and equivalents thereof.
Teo, Jiunn, Ford, Cheryl, Schmidt, Leslie
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