CA1062413A

CA1062413A - Polycarbonate membranes and production thereof

Info

Publication number: CA1062413A
Application number: CA222,510A
Authority: CA
Inventors: Willard S. Higley; Paul A. Cantor; Bruce S. Fisher
Original assignee: UNITED STATES (THE GOVERNMENT OF THE)
Current assignee: UNITED STATES (THE GOVERNMENT OF THE)
Priority date: 1974-03-26
Filing date: 1975-03-19
Publication date: 1979-09-18
Also published as: FR2265807B1; GB1500937A; CH594434A5; NL172920B; NL172920C; IT1030266B; NL7502865A; DK163482B; NO135162C; NO135162B; FR2265807A1; DK163482C; JPS5228826B2; BE826775A; SE407583B; SE7503430L; JPS5179172A; DK96275A; NO751026L

Abstract

POLYCARBONATE MEMBRANES AND PRODUCTION THEREOF

ABSTRACT OF THE DISCLOSURE

Polycarbonate membranes useful for hemodialysis are fabricated from polyether-polycarbonate block copolymers by a water gelation process. The process comprises casting on to a substrate surface a layer of a multicomponent casting solution comprising the copolymer dissolved in a water-miscible organic solvent together with a cosolvent which acts as a swelling agent for the copolymer, drying the layer to partially evaporate the solvents therefrom, immersing the partially dried layer in water to form a gelled membrane, and stripping the gelled membrane from the substrate surface. The membrane has improved strength and improved permeability to solutes in the "middle molecule" range while maintaining clinically acceptable ultrafiltration rates and clearance of low molecular weight solutes.

Description

- ~\
`` 1062413 This invention relates to new and improved polycarbonate membranes and their production, and-particularly to such mem-branes which are especially useful or hemodialysis.
Hemodialysis membranes for use in the artificial kidney are at the present time generally made of cellophane~
materials. The best of these materials currently available for such purpose has been found to be a cellulose regenerated from a cupro-ammonium jolution, plasticized with glycerol and identified by the registered trademark "Cuprophan"*. Although Cuprophan~ membranes provide ultrafiltration rates and clear- -ance of low molecular weight solutes within the desirable ranges for proper hemodialysis, they still have many deficiencies which prevent them from being completely satisfactory as hemo-dialysis membranes. Certain toxins wh~ch it is thought necessary to remove from the blood by hemodialysis are "middle molecules", i.e., molecules of molecular weights in the range of 300 to 5,000. Such middle molecules pass through Cuprophan~ membranes at rates much slower than is desirable. Additionally, the burst and tear strengths of Cuprophan~ membranes are lower than is desirable in materials employed in hemodialysis and their shelf-life is low, apparently due to migration of plastic-izer during storage. Further, the permeability of the Cuprophan~ membranes has been found to vary from batch to batch and to decrease on aging. Lastly, it is very difficult to cause adhesion between Cuprophan~ and other materials and between Cuprophan~ and itself. Thus it is difficu1t to utilize improved hemodialyzer designs requiring *manufactured and sold by Enka Glantzstoff of Wuppertal Germany -z4~3 leak proof compartments which depend upon the membrane materlal for sealing o~f blood from dialysate ~olution and blood and dialysate solutions from the atmosphere.
The membranes preparea from the present inve~tion are significantly improved over the state-of-the-art .; .
materials e.g. Cuprophan~in the following areas.
1. Polycarbonate membranes permit clearance of critical "mlddle molecules" up to three times greater than Cuprophan in comparabla tests. ~ . .

2. The burst strength of polycarbonate ~embranes ~si 1.5-2 time~ that of Cuproph ~.

3. The latltude of membrane properties achievable ~
with polycarbonate~ i9 con~iderable and can be arranged ln accordance with desired needs.
f 15 4. Pol~carbonate membranqs are stiffer than Cuproph ~ in the wet state. This property results in thinner blood layer~ in dialyzers, more efficient dialysis ~nd lower blood priming volume. ~ ~-. . 5. Polycarbonates are heat-sealable wet or dry per- :
mitting wide Iatitute in dialyzer design.
6. Due to greatex efficiency of dialysi~ with poly-carbonate m~mbranes, projections indicate a greatly re-duced dlalysi~ time ~9 hr~/wk) compared with Cuprophan~
. .. . . .
.. In attempting to develop hemodialysis membranes with . -10t~2413 .
mechanical and transport properties superior to those of Cuprophan, it has previously ~een proposed, by two of the present co-inventors, to fabricate membranes of polyether-polycarbonate block copolymers containing a balance of hydro-phobic aromatic polycarbonate blocks, which i~part toughness, ' and hydrophilic polyether blocks, which impart water and solute permeability. The polyca~bonate system was ~hosen for dialysis membrane development because of the outstanding mech-anical properties shown by commercial polycarbonate, the very low thrombogenicity exhibited by properly heparinized poly-car~onate surfaces, the ease of forming this polymer typP
~- into various configurations such as films and ~i~ers, and the.~ many synthetic possibilities for chemical modifi~ation of the - basic aromatic polycarbonate backbone st-ructure to achieve ~ 15 desired membrane transport properties. As disalosed in the .
"Proceedings of the 5th Annual Contractors' ~onference of the .
Artificial Kidney Program of the National Institute of Arthritis and Metabolic Diseases", U.S. Department of Health, ~ducation and Welfare (1972), pages 32-33, gelled membranes were prepared from polyether-polycarbonate block copolymers by means of the phase inversion technique, i.e., casting a solution of the copolymer in a suitable solvent on to a sub-strate suxface to form a layer which is allowed to dry onl~
partially and which is then immersed in a liquid gelation medium in which the copolymer is insoluble bu~ which is ~ miscible with the solvent, employing chloroform as the casting `~ sol-vent and methanol as the gelation medium. The gelled mem-.
:i i branes resulting from such proceaure, while exhibitin~
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" ' ', . " ' ~ ~ ' ,' ~ ' ', ' ' ~ " 106Z413 considerable superiority over Cuprophan~membranes in their permeabilities to solute~ in the middle molecule range, were found, however, to possess several drawbacks to their practical use as hemodialysis membranes. First of all, their ultrafiltrati~n rates were 2 to 5 ~imes that of Cuprophan~
membranes, which would be clinically unacceptable for hemo-dialysis as presently administered due to the possibility of dehydration of the patient occurring during treatment.
Secondly, their burst strength was no more, and in many cases, less than that o~ Cuprophan~membranes~ Thirdly, attempts at continuous casting of the membrane on production-type machinery in widths suitable for use in commercial hemodialyzers, pre3ented further problems which rendered the me~hanol gela-tion procedure impractical for commercial hemodialysis membrane production.
- The most serious problem encountered was the frequent occurrence of gross leakage of albumin through the membranes during ultrafiltration testing, and which was found to be attributable to holes or other imperfections in the ultrathin ~urface of the membrane which form~ the barrier between the blood and the dialysate or flushing solution. All o these membranes are referred to as being "anisotropic" or "skinned", which means that their two sides are significantly different from each other, one side belng relatively smooth and the other ~ide being relat~vely rough and porous. The smooth side is ~-the "barrier" layer which aces the blood during hemodialysis and is ~uite thin, on the order of 0.05 to ~.2 micron~. The ,' remainder of the membrane merely function~ as a support struc-.

1~6~4~3 i 1:
ture and is about 25 to 30 microns in thickness. The int~grity of the barrier layer is crucial to the performance of the mem-brane in dialysis. Any perforation, puncture or othier com-promise of the integrity of the barrier layer destroys thie S usefulness of the membrane and all materials in contact with thie membrane merely leak through. It has now been proven by electron microscopy that the methanol-gelled polycarbonate membraines are formed with their barrier layer on the side of ¦
the membrane contacting the casting surface rathier than the ¦
side of the me~brane facing the air during d ning. Thie I
signi~icance of this fact is thiat continuous casting of these ¦`
~ membranes on production-type machinery involves continuously ;~ peeling thie delicate barrier layer of of the casting surface ., . .
during the process, making i~ almost imipossible to maintain the integrity of the barrier layer and obtain a membrane ~ suitable for use in hemodialysis. Also, it was found that -~ long term exposùre of the membrane to methanol affects the 1 - me~brane properties, thereby necessitating the quick and extensive flushi~g or washing of the membrane to remove the methanol therefrom and replace it with water in order for the membrane to have adequate shelf-life. One additional problem ,, .
presented was the impracticality of employing large volumes o~ methanol as the gelation medium due~to the cost, toxicity ;~
,~ and flammability of this material.
.` 25 Tt i9 therefore an object of the present invention to ' provide hemodialysis membranes having improved permeability to solutes in the middle molecule range as compared with -~ presently available hemodialysis membranes, while maintai-ning ;

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06Z4~3 clinically acceptable ultrailtratio~ rates and clearance ' of low molecular weight solutes..
Another object of the invention is to provide hemo- :
dialysis membranes having improved burst and tear strengths ~ .
as compared with presently available hemodialysis membranes.
A further object of the invention is to provide .
hemodialysis membranes having improved shelf-life as compared .
with presently available hemodialysis membranes. A further object of the present invention is to provide hemodialysis membranes having improved sealability over presently available hemodialysis membranes making possible leak-proof hemodialyzer compartments through simple heat-sealing of the membranes.
Still another object of the invention is to provide a process for producing gelled polycarbonate membranes useful for hemodialysis and having the improved properties as set forth in the preced.ing objects, which is easily and economically adaptable to large scale machine production without impairing the integrity of the barrier layer of the membrane, ' The above and other objects are achieved in accordance .. ' with the present,invention by producing a gelled polycarbonate membrane from a polyether-polycarbonate block copolymer by the `'' phase inversion technique employing an aqueous gelation system with water as the gelling medium and a water-miscible organic ' solvent as the casting solvent, More speciically, the pro-cess compri.ses casting on to a substrate surace having a " smooth finish, a layer of casting solution comprising a poly-'~ ether-polycarbonate block copolymer containing from about 5 to about 35% by weight of the polyether component and a water-miscible organic solvent together with a cosolvent which '~ 30 acts as a swelling agent for the copolymer, drying the layer :.~ - 5 ~

L062~3 to partially evaporate the solvents therefrom, immersing the partially dried layer in water to form a gelled membrane, and stripping the resulting gelled membrane from the substrate surface.
It has been found that gelled polycarbonate membranes produced in this manner, with water as the gelling medium, are formed with their barrier layer on the side of the membrane facing the air during drying, rather than on the side of the membrane in contact with the casting surace as is the case with methanol-gelled polycarbonate membranes, which enables the gelled membrane to be readily stripped from the casting surface without impairing the integrity of the delicate barrier layer, thereby rendering large-scale machine production of such membranes practical. The use of water as a gelling medium in place o methanol also facilitates large scale machine produc-tion in that water i9, of course, less expensive, non-toxic and non-flammable, and also eliminates the necessity or the extensive flushing or washing of the membrane to remove the gelling medium therefrom as was required in methanol gelation.
It has also been found that the water-gelled polycarbonate membranes have considerably higher strength than either the ` methanol-gelled polycarbonate membranes or Cuprophan~ membranes.
Gelled polycarbonate membranes fabricated in accordance with s~ the present invention have furthermore been found to be considerably superior to Cuprophan~ membranes in their perme-` abilities to solutes in the middle molecule range while maintain-ing ultrafiltration rates and clearance of low molecular weight solutes comparablé to that of Cuprophan~ membranes.
Moreover, it has been found that the ultrafiltration rates of the membranes abricated in accordance with the present inven-;i ~ - 6 -L06;~ 3 .

tion are controllable to level~ comparaSle to those of Cupro~
phan membranes by proper selec~ion of the molecular weight of the polyether-polycarbonate block copolymer used in fabricating the membrane.
The polycarbonate material ~rom which the-improved hemo-dialysis membranes ar~ fabricated in accordance with the present invention is a polyether-polycarbonate block copolymer preferably containing from about 5 to a~out 35% by weight of the polyether component. It ha3 been found that this propor-tion of polyether blocks renders the normally hydrophobic . ~--. , : .,.
polycarbonate sufficiently hydrophilic 80 as to make it suita`ble for use as a hemodialysis membrane. Such block copolymers may be prepared, for examp1~ by the method of Goldberg (Journal of ;' Polymer Science: Part C, No. 4, pp. 707-730 tl963I) wherein a comonomer mixture of from about 95 to about 65~i by weight o~
2,2-(4,4'-dihydroxydiphenyl)propane, generally known as " . . .
bisphenol A, and correspondingly rom about 5 to about 35% by ~ weight of a polyether glycol such as po~yethylene glycol, isi reacted with a carbonic acid derivative such as phosgene. A
polyethylene glycol which is found to be particularly suitable ~, is Carbowax 6000, which is a polyethylene glycol having an average molecular weight of 6700, although polyethylene glycols o other molecular weights can also be u~ed, such as, for .. ~ * * *
example, Carbowax 600, Carbowax 1000 and Carbowax 4000, which are polyethylene glycols having molecular weig~ts of 600, 1000 and 4000, respectively. Polyether glycols other than poly-ethylene glycol~i can also be used, such a~, for example, polypropylene oxide-polyethylene oxide block copolymers as *C~rhow~x is ~ Registere~ Tra~emaxk of Union Carbide Corp.
,,. ~ . .

, . .. . . . .. .. ., i . . . . ~.. ~ . . . .... . . . , . . , . . ' ., 1062~L3 exemplified by members of the Pluronic ~iol series such as Pluronic F68. (Pluronic is a r~gis~ered trademark o~ Wyandotte Chemical Co. ) Polyether-polycarbonate block copolymers having molecular weights ranging from about 50,000 to about 750,000 may suitably be prepared in the above manner. A p~eferred range of mole-cular weights is from about 200,000 to about SOO,OOOj since it has been found that membranes fabricated in accordance with the present invention from polyether-polycarbonate block copolymers having molecular weights within such preferred range exhibit ultraflltration rates comparable to those of Cuprophan membranes and hence within the range clinically i acceptable for use in hemodialysis.
Casting solutions for use ~n the process of the present in~ention are prepared by dissolving the polyether-polycarbon-ate block copoiymer in a water-mlscible organic solvent for the copolymer. The solvent preferably has a boiling point within the range of 50 to 85C for optimum room temperature ca~ting. The preferred solvent is 1,3-dioxolane which has the ; 20 appropriate combination of high solvent power for the copolymer, water-miscibility and a boiling point of 75 to 76C. Okher suitable solvents which can be employed include 1,3-dioxan, 1,4-dioxan, tetrahydrofuran, butyrolactone, acetonitrile, cellosolve acetate, dimothylformamide, pyridine and mixtures thereof. Ch}oroform, which was previouqly suggested for use . . . .
as a casting solvent in the methanol-gelation of polycarbonate membranes, is not suitable since it is not water-miscible.
The casting ~olutions are generally formulated to have a ` total solids content o from about 1 to about 20 weight ~ to i j!
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~062413 give dopes ranging in viscosity from about 5,000 to about 30,000 cps. Typically, ~olid~ contents range from about 10 to about ~0 weight % to give viscosities of from about 7,000 to about ~,000 cps, the preferred range. A swelling agent, S such as dimethyl sulfoxide, is advantageously added to the casting solution in amounts ranging from about 10 to about 75% by weight of the copolymer, the preferred range being from about 15 to about 25% by weight of the`copolymer. The addition of the swelling agent has been found to enhance ~he permeability of the resulting membrane. Other swelling agents - which have been empl~yed include dimethylformamide,~dimethyl-.i . ; ~ , .
acetamide, acetam1de, formamide and pyridine.
~ Productlon of the polycarbonate membrane aan be effected ; on a continuous basis by doctor blade casting o the casting solution on to a moving surface having a smooth~finish, such as a coated release paper, ~ ~ !The well-i ~ .
filtered (10 ~m) casting solution is prefersbly supplied to a hopper placed in front of the doctor blade by means of a ` positive displacement metering pump;. The hopper is provided with end guides for controlling the width of the membrane sheet. Th~ thickness of the membrane sheet is controlled by adjusting ~he gap be~ween ~the knife and the moving belt 8ur-. 4 face, which i9 usually set 80 as to give a final membrane thickness of l.O-l.S mils.
The freshly cast and wet film is allowed to air dry at temperatures ranging from abou~ 20 to about 30C for periods ranging from about 1.0 to about S.O minutes to partially evaporate the solvent there~rom, the drying time being deter-,, . . . ~

106Z4~3 mined by both the belt ~peed and ~he drying distance. The partially dried film is gelled to produoe the final membrane by immersion, while still adhering to the moving belt, in a water bath. The gelation bath temperature may be varied bet-ween about zero to about 40C, the preferred range being 20 to 30C. After gelation, the membrane is peeled from the mov-ing belt and rolled up separately from the belt on to a cylindrical core. The membrane is finally washed thoroughly with deioni~ed water to remove the last traces of solvent and swelling agent and stored in a sealed plastic ~ag or othe~
container containing water and a sterilant such as formaldehyde.
The final thickness o~ the membrane generally varies from about 1.0 to 1.5 mils, depending upon the knife gap setting, casting solution viscosity and belt speed~
~ 15 The following examples are given for the purpose of ; illustrating the present invention.
Example 1 A mixture of 491 gm of ~he polyether-polycarbonate bloc~
copolymer obtained by reacting phosgene with a comonomer mix-ture of bisphenol A ~5 wt %) and Carbowax~6000 ~25 wt %), and ,, having an intrinsic viscosity of 1.7 (in chloroform at 25C) corresponding to a molecular weight of 377,00~ , 3146 gm of , 1,3-dioxolane and 98.2 gm of dime~ yl sul~oxide, was ~lowly , . .
agitated until solution was effected (approximately 8 hours).
The crude solution was filtered in a pre~sure filter at 30 to SO p~ig through a polypropylene felt or 25 ym porosity ` asbe~tos sheet medium to remove a small re~idue of fine inso~uble matter. The resulting casting solution has a vis-: :, , -- 10 --: h ~osity of 16,000 cps at 25C.
Approximately one-half gallon of the above 10 ym filtered '' castlng solution was cast via a doctor blade on to the surface of a 16 inch wide moving belt moving at a S speed of 2 . 36 feet per minute . The hopper end guides were set to provide a cast film width of 15 1/2 inches and the gap between thè doctor knife and the moving belt surface was set at 7.0 mils. These dimensions provide samples suitable for use in the Kiil dialyzer. ~ total drying time for the cast ~ilm of 2.54 minutes was allowed before gelation in a watex ' bath. The ambient air temperature was maintained at 24.7 0.4~C and the gelation water bath temperature at 25 ~ ~.5C.
After gelation, the resulting membrane was peeled from the ~oving belt and rolled up separately rom the belt on to a lS cylindrical core. A total o 177 eet of membrane was thus ;; produced during a period o 75 minutes. ~he m~'mbrane was washed in a fl~wing stream of deionized water and stored in a sealed polyethylene bag containing 2% aqueous ~ormaldehyde.
'~' The polyca~bonate membrane fabricated as above was found ', , ~, 20 to have physical and permeability properties ~s set forth in ; 'Ta~le 1, below. For purposes of comparison, correspon,ding valu~s are given for a typical sample of Cuprophan PT150 mem-brane. The permeability propertles were determined in a dialysis test cell o the type designed by the National ' 25 Bure~u of Standards.
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~6Z9~L3 ab ~e _ . _ _. ~-~ t~
Polycarbonate Mem~ Cuprophan PT 150 . brane of Example l Membrane , . _ . _ _ Wet Thicknes~, mils 1~ 3 0.9 .
Relative Burst Strength, .
Cm Hg. 30 20 Ultrafiltration Rate at 37C, 200 mm Hg~P, .
ml/m2-hr-mm Hg 3.6 3.9 Diffusive permeabilit~, . .
at 37C, cm/min(x 10 ) .
(Solute molecular wei-ght in parenthesis) .
Sodium chloride ~58. 4 ¦ 709 ~ 707 Vitam~n B12 ( 1355) 101 46 Human Serum .
Albumin (~0,000) 0 . 0 _ _ _ _ _ __ ~ _ It aan be seen from the data in Table 1 that the poly-carbonate membrane fabricated in accordance with the present invention, with approximately 40~ greater thickness than the Cuprophan~membrane, and approximately the ~ame ultrafiltra-tion rate and permeability towards ~odium chlorida, a rep-resentativo low molecular weight solute in blood, exhibits a 50% higher burst strength and a 120% higher permeability to-ward Vitamin B12, a model medium molecular weight solute, while being completely impermeable to serum albumin, a high molecular weight component of blood whose removal from the blood during hemodialysls i~ not desirable.
Xt has further been ound ~hat the pol~carbonate mem-brane preparad in accordance with the presen~ invention is considerably sti~fer in its wet state ~han Cuprophan mem- !
branes. This i5 of importance in hemodialysis in maintaining a thin blood ~ilm, a greater area o blood for dialysis, and a low blood priming volume. Also, the polycarbonate membrane of the present invention iæ heat sealable, making possible greater latitude in hemodialyzer design~ Furthermore, the polycarbonate m~brane of the present invention has proven - 12 ~

2~3 , to be non-toxic in a battery of in vitro ana animal tests, is blood compatible, and its thrombogenicity is approximately the same as Cuprophan~ membranes in vitro.
Examination of the polycarbonate membrane prepared in accordance with Example 1, employing water as a gelation medium, by scanning electron photomicrography showed the side of the membrane which was facing the air during drying to be smoother and more regular than the side of the membrane which was in contact with the casting surface, indicating that the ; 10 membrane was formed with its barrier or active layer on the - side of the membrane facing the air during dryiny rather than on the side of the membrane in contact with the casting sur-face as was the case with methanol-gelled polycarbonate mem-branes. Hence, the continuous peeling of the membrane from the moving belt surface has no deleterious efect on the .
delicate barrier layer of the membrane, making large scale machine production of the membrane feasible. The water-gelled polycarbonate membrane prepared in accordance with Example 1 also appeared to have a much finer and more uniform ultragel structure than a similar membrane prepared by methanol , gelation. This is reflected in the considerably higher i strength of the water-gelled polycarbonate membranes, which were found to have burst strength S0 to 70% greater than the 1 corresponding methanol-gelled polycarbonate membrane.
Hence, it can be seen that the process of the present i;l invention enables large scale machine production of poly-;'~,',"
carbonate membranes which are useful for hemodialysis and which exhibit improved strength and improved permeabilities . :'i l to solutes in the middle molecule range as compared with :
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106Z4~L3 presently available hemodialysis membranes, while maintaining ultrafiltration rates within the clinically acceptable range to avoid dehydration and also maintaining clearance of low molecular weight solutes within the clinically acceptable range to avoid low molecular weight depletion syndrome.
Example 2 This example shows the efficacy of swelling agent added to the casting solution formulation in enhancing the water and solute permeability of polycarbonate membranes prepared accord-ing to the present invention.
Gelled membranes were case under identical conditions from casting formulations containing a polyether-polycarbonate block copolymer obtained by reacting phosgene with a comonomer mixture of bisphenol A (75 wt %) and Carbowax~ 6000 (25 wt %) and having an intrinsic viscosity of 1.2 (in chloroform at 25cj/ corresponding to a mol. wt of 190,000. The casting solution formulations contained varying amounts of the swelling agent dimethyl sulfoxide (DMSO). The properties of the result-ant polycarbonate membranes as a function of the amount of DMSO swelling agent in the casting formulation are summarized in Table 2. Corresponding values for a typical sample of Cuprophangg PT-150 are given for comparison.

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f 106Z9L~3 m e data of Table 2 clearly show the marked effect of adding DMS0 to the casting solution on the degree of membrane swellin~, as measured by membrane wet thickness and water con-tQnt, with resultant enhancement o~ membrane permeability to S water and a variety of solutes. The polycarbonate membrane prepared using the casting formulation containing no swelling agent exhibited permeability-properties comparable to those of a typical Cuprophan PT150 membrane. Addition of the first increment of DMS0 swelling agent (2 grams per 15 grams of poly-mers) to the casting formulation is seen to have near~y doubled the water content and tripled ~he hydraulic permeability (as ~`measured by u~trafiltration rate) of the membrane, and increased the permeability to all the ~olutes tested. The degree of permeability enhancement increased with solute molecular size, with 24-37~ higher values observed with the smaller solutes, ~uch as urea and areatinine, and a very marked increase of 160~ found for inulin, a model solute representative of ~he upper "middle molecule" range. Further increase in the level of swelling agent in the casting formulation ~to 4 grams per 15 grams of polymer) is seen to have still ~urther increased the polycarbonate membrane water content and water permeability, only slightly ~2-7~1 increased smaller solute permeability . .
~i.e. sodium chloride, urea, creatinine and uric acid)`, while ; still resul~ing in a substantial incre~ase in "middle molecule"
permeability 122, 24 and 6g% increase for phosphate, raffinose and inulin respectively~. Significantly, the polycarbonate me~branes completely reject aIbumin even when substantial amounts of swelling agent are added to the casting ~ormulation.

6Z~13 This example serves to ~llustrate the effectiveness of several cosolvents - swelling agents or enhancing polycarbon- .
ate membrane permeability when added to the membrane casting solution formulation.
Ca~ting solutions were prepared from the following for-mulation, u~ing a polyether-polycarbonate block copolymer bbtained by reacting phosgene with a comonomer mixture of bisphenol A ~75 wt %) and Carbowax 6000 525 wt %) and having.
an intrinsic viscosity ~in chloroform at 25C) of 1.52 corres-ponding to a molecular weight of 301,000.

- COMPONE~T . WEI GHT - GRAMS
Polyether-Polycarbonate ~.. ..
Block Copolymer 40.0 1,3-Dioxolane . 25 .2 Swelling Agent .. ; . # . 0 Membranes were prepared ~rom each ~ormulation by hand casting und~r identical condi~icns ~n glass plate~ at room ! temperature and gelling in water at 25C after varying drying ~! , periods. The physical ana permeability properties found for .~ 20 these membranes are shown in ~able 3.
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~06;~:13 The data outlined in Table 3 indicate that, a~ter approp-riate adjustment of drying time before gelation, polycarbonate : membranes of equivalent strength and permeability character-~ stics can be prepared through formulation with any one of the 5 three swelling agents, pyridine, dimethyl formamide and dimethyl : sulfoxide.-: : , ~ . ~ , j .
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Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for producing a polycarbonate membrane useful for hemodialysis which comprises casting on to a sub-strate surface having a smooth finish a layer of casting solution comprising a polyether-polycarbonate block copolymer containing from about 5 to about 35% by weight of the polyether component and a water-miscible organic solvent together with a cosolvent which acts as a swelling agent for said copolymer, drying said layer to partially evaporate the solvents therefrom, immersing said partially dried layer in water to form a gelled membrane, and stripping said gelled membrane from said substrate surface.

2. The process of claim 1 wherein said polyether-poly-carbonate block copolymer has a molecular weight within the range of from about 50,000 to about 750,000.

3. The process of claim 1 wherein said polyether-poly-carbonate block copolymer has a molecular weight within the range of from about 200,000 to about 500,000.

4. The process of claim 1 wherein said polyether-poly-carbonate block copolymer comprises the polymerization reaction product of phosgene with a mixture of from about 95 to about 65% by weight of bisphenol A and correspondingly from about 5 to about 35% by weight of a polyethylene glycol, having a molecular weight in the range of 600 to 6,000.

5. The process of claim 1 wherein said solvent has a boiling point in the range of from about 50 to about 85°C.

6. The process of claim 1 wherein said solvent comprises 1,3-dioxolane.

7. The process of claim 1 wherein said casting solu-tion contains from about 1 to about 20 weight % of total solids and has a viscosity within the range of from about 5,000 to about 30,000 cps.

8. The process of claim 1 wherein said casting solu-tion contains from about 10 to about 20 weight % of total solids and has a viscosity within the range of from about 7,000 to about 25,000 cps.

9. The process of claim 1 wherein said cosolvent-swelling agent is present in said casting solution in amounts ranging from about 10 to about 75% by weight based on the weight of said copolymer.

10. The process of claim 9 wherein said cosolvent-swelling agent is present in amounts ranging from about 15 to about 25% by weight based on the weight of said copolymer.

11. The process of claim 9 wherein said cosolvent-swelling agent is selected from the group consisting of dimethyl sulfoxide, dimethyl formamide and pyridine.

12. The process of claim 9 wherein said cosolvent-swelling agent comprises dimethyl sulfoxide.

13. The process of claim 1 wherein the layer of casting solution is air-dried at temperatures ranging from about 20 to about 30°C for a period ranging from about 1.0 to about 5.0 minutes prior to being immersed in said water.

14. The process of claim 1 wherein said water is main-tained at a temperature ranging from about 20 to about 30°C.

15. A membrane of a hydrophilic polycarbonate copolymer consisting of 5 to 35% by weight of repeating alkylene ether carbonate units and from 95 to about 65%
by weight of repeating bisphenol A-carbonate units, said copolymer having a molecular weight within the range of from 200000 to about 750000 as determined by intrinsic viscosity measurement, said membrane having a thickness of about 1 to 1,5 mils (25 to 37.5 microns) and having the property when used in a hemodialysis apparatus of preferentially removing middle molecular weight molecules from blood,

16, The membrane of claim 15 wherein said poly-carbonate copolymer comprises the polymerization reaction product of phosgene with a mixture of from about 95 to about 65% by weight of Bisphenol A and correspondingly from about 5 to about 35% by weight of a polyethylene glycol, having a molecular weight in the range of 600 to 6,000.

17, The membrane of claim 15 which is produced by the process which comprises casting onto a substrate surface having a smooth. finish a layer of casting solution having a viscosity within the range of from about 5,000 to about 30,000 cps and comprising said polycarbonate copolymer and a water-miscible organic solvent together with. a cosolvent which acts as a swelling agent for said copolymer, drying said layer to partially evaporate the solvents therefrom, immersing said partially dried layer in water to form a gelled membrane, and stripping said gelled membrane from said substrate surface.

18. The membrane of claim 17 wherein said solvent has a boiling point in the range of from about 50 to about 85°C.

19. The membrane of claim 17 wherein said solvent comprises 1,3-dioxolane.

20. The membrane of claim 17 wherein said casting solution contains from about 1 to about 20 weight percent of total solids.

21. The membrane of claim 17 wherein said casting solution contains from about 10 to about 20 weight percent of total solids and has a viscosity within the range of from about 7,000 to about 20,000 cps.

22. The membrane of claim 17 wherein said cosolvent-swelling agent is present in said casting solution in amounts ranging from about 10 to about 75 percent by weight based on the weight of said copolymer.

23. The membrane of claim 22 wherein said cosolvent-swelling agent is selected from the group consisting of dimethyl sulfoxide, dimethyl formamide and pyridine.

24. The membrane of claim 17 wherein the layer of casting solution is air-dried at temperatures ranging from about 20 to about 30°C for a period ranging from about 1.0 to about 5.0 minutes prior to being immersed in said water.

25. The membrane of claim 17 wherein said water is maintained at a temperature ranging from about 20 to about 30°C.