CA1310160C - Porous polypropylene hollow fiber membrane, method for production thereof and artificial lung - Google Patents
Porous polypropylene hollow fiber membrane, method for production thereof and artificial lungInfo
- Publication number
- CA1310160C CA1310160C CA000560896A CA560896A CA1310160C CA 1310160 C CA1310160 C CA 1310160C CA 000560896 A CA000560896 A CA 000560896A CA 560896 A CA560896 A CA 560896A CA 1310160 C CA1310160 C CA 1310160C
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- membrane
- polypropylene
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- film type
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Abstract
A flat-film type porous polypropylene membrane possessing a microreticular structure is disclosed which is characterized by the fact that either or both of the opposite surface region of the porous membrane forms a surface layer possessing an average pore diameter in the range of 0.1 to 5.0µm, a bubble point of not more than 2.0kgf/cm2, a porosity in the range of 60 to 85%, and a water permeability of not less than 100 m1/min.mmHg.m2 and the membrane possesses a wall thickness in the range of 30 to 300 µm. When this flat-film type porous polypropylene membrane is used for blood plasma separtion, it effects the blood plasma separated at a high speed and sparingly entails occlusion of blood cells or hemolysis.
Description
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SPEC IFICATION
POROUS POLYPROPYLENE MEMB~ANE ~ND METHOD
FOR PRODUCTION THEREOF
BACKGROUND OF ~HE INVENTION
5 tFiled of the Invnetion]
This invention relates to a porous polypropylene membrane and a method for the production thereof. This invention also relates to a flat film type porous polypropylene membrane to be used for blood 10 plasma separation, i.e. separation of blood into blood cells and blood plasma, and for removal of bacteria from blood and a method for the production thereof. More particularly, this invention relates to a flat-film type porous polypropylene membrane which, when used for the 15 blood plasma separation, exhibits a high blood plasma separa-tion speed and has only a sparing possibility of incurring such adverse phenomena as leakage of part of the blood cells in the blood plasma after the blood-plasma separation and hemolysis and a method for 20 the production thereof.
[Description of the Prior Art]
Heretofore, vrious permeable membranes have been adopted for the purpose of separating blood into blood cells and blood plasma. These permeable membranes 25 are used for blooa plasma purification aimed at removal of abnormal protei~s, antigens, antibodies, and immune complexes in such diseases due to abnormal immunity as systemic lupus erythematosus, rheumatoid arthritis, glomerular nephritis, and myasthenia gravis, for 30 manufacture of blood plasma preparations for component transfusion, and for pretreatment of artificial kidneys, for example. As examples of the permeable membranes heretofore used for the blood plasma separation mentioned above, there can be cited a cellulose acetate 35 membrane (applicant's Japanese patent Unexamined Publication SHO 54(1979)-15,476, publishe~ February 5, 1979) and a polyvinyl alcohol membrane, a '.
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polyester membrane, a polycarbonate membrane, a polymethyl methacrylate membrane, and a polyethylene membrane (applicant's Japanese Patent Unexamined Publication SH0 57(1982)-84,702, published May 27, 1982).
5 These parmeable membranes are deficient in mechanical strength, porosity, and plasma separating ability. When these permeable membranes are used in the blood plasma separation, owlng to the clogging of the micropores therein, the erythrocytes lO are injured and the components of complement in the blood plasma are activated and the separated blood plasma is seriously injured as the result.
A permeable membrane has been proposed which is produced by mixing a polymer such as a crystalline 15 polyolefin or polyamide which is sparingly soluble in a solvent and is stretchable and a compound partially compatible wi-th the polymer and readily soluble in the so]vent, molding the resultant mixture in the form of film, sheet, or a hollow article, treating the shaped 20 article with the solvent, drying the treated shaped article, and then uniaxially or biaxially stretching the dried shaped article to an extent fallng in the range of 50 to 15,000% (applicant's Japanese Pa~ent Publication SHO
57~1982)-20,970, published May 4, 1982). Since this 25 membrane has been stretched for the purpose o~ increasing pore diameter, it is susceptible of thermal shrinkage so much that, when the permeable membrane is used in a medical device, it will not be ab]e to be safely sterilized in an 30 autoclave. Moreover since the micropores are formed by stretching in the permeable membrane, they are linear micropores substantially parallel to the direction of thickness of the membrane. Since the micropores have a substantially uniform shape in the opposite surfaces and 35 in the interior of the wall of the membrane, they are inevitably clogged with proteins and blood cells when the permeable membrane is used in the blood plasma separation.
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As concerns permeable membranes for use in the blood plasma separation, polyolefin type macromolecules hav~ been attracting attention as materials experiencing activation of complements only to a nominal extent and 5 e~celling in bio-adaptability. At present, studies are underway on the feasibility of permeable membranes using such polyolefin type macromolecules. For example, there has been discloses a method for the produc-tion of a porous membrane, which comprises preparing a molten lO mixture consisting of lO to 80% by weight of a paraffin and 90 to 20% by weight of a polypropylene resin, extruding the molten mixture through a die in the form of a film, a sheet, or a hollow fi.ber, suddenly solidifying the molten extruded mixture in water kept at 15 a temperature of not more than 50C, and then separating the paraffin from the shaped article by extraction (applicant's Japanese Patent Unxamined Publication SHO
55(1980)-60,537, published May 7, 1980). The porous membrane which is obtained 20 by this method, however, cloes not fit speedy blood plasma separation because the membrane has been suddenly cooled with water, a substance of a large specific heat, and, as the natural consequence, the pores formed in the surfaces and those formed in the interior of the 25 membrane have small diameters and the porosity is low and the speed of permeation is proportionately low.
As means of cooling and solidlfying the aforementioned molten mixture, there have been proposed a method which uses a metallic roller and a method which 30 uses a cooling and solidifying liquid such as a paraffin possessing highly desirable compatibility with the aforementioned organic filler (ap~licant's Japanese Patent Application SH0 60(1985)-237,069 corresponding to Japanese Patent Unexamined' Publication SHO 62(1987)-97,603, 35 published May 7, 1987). The former method produces a porous membrane which possesses surface pores of an extremely small diameter and, therefore, passes blood plasma only at a low speed. In the latter method, since the cooling and so].idifying liquid has a small , 1 3 ~
specific heat as compared with water and, therefore, promotes the crystallization of polypropylene at a proper cooling rate, the membrane is enabled in the interior thereof to form micropores of a large diameter 5 enough for the purpose of blood plasma separation and is suffered in the surface regions thereof to form a very large reticular structure which is believed to arise becaue the polypropylene in the surface regions is dissolved out into the cooling and solidifying liquid 10 before it is allowed to solidify. In the porous membrane possessing such surface layers as described above, the surface layers each function as a prefilter.
Thus, the porous membrane is capable of carrying out the blood plasma separation at a highly desirable speed 15 without surffering proteins and blood cells to clog the micropores. When this porous membrane is brought into contact with blood, however, it is liable to occlude blood cells, which may possibly be forced to liberate homoglobin under application of pressure.
An object of this invention, therefore, is to provide an improved porous polypropylene membrane and a method for the production thereof. ~nother object of this invention is to provide an improved flat-film type porous polypropylene membrane and a method for the 25 production thereof. A further object of this invention is to provide a flat-film type porous polypropylene membrane to be used for blood plasma separation aimed at separting blood into blood cells and blood plasma and for removal of bacteria from blood and a method for the 30 production thereof. Yet another object of this invention is to provide a flat-film type porous polypropylene membrane which, while being used for blood plasma separation, permits the blood plasma separation to proceed at a high speed, suffers the separated blood .
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plasma to be injured only sparinglyr and has little possihility of entailing occlusion of blood cells or hemolysis and a methocl for the production thereof.
[Deisclosure of the Invention]
The objects described above are accomplished by a flat-film type porous polypropylene membrane possessing a microreticular structure, characterized by the fact that either or both of the opposite surface region of the porous membrane forms a surace layer 10 possessing an average pore diameter in the range of 0.1 to 5.0~m, a bubble point of not more than 2.0 kgf/cm2, a porosity in the range of 60 to 85~, and a water permeability of not less than 100 ml/min.mmHg.m2 and the membrane posesses a wall thickiness in the range of 30 15 to 300~m.
This invention also discloses a flat-film type porous polypropylene membrane, wherein the bubble point of the membrane is not more than 1.8 kgf.cm~. This invention further discloses a flat-film type porous 20 polypropylene membrane, whrein the water permeability is not less than 140 ml/min.mmHg.m2. Further this invention discloses a flat-film type porous polypropylene membrane, wherein the shrinkage ratio after 120 minutes' heat treatment at 121C is not more 25 than 6.0~.
The object descrbied above are further accomplished by a method for the production of a flat-film type porous polypropylene membrane, chaxacterized by mixing 100 parts by weight of 30 polypropylene, 200 to 600 parts by weight of an organic filler uniformly dispersible in the polyperopylene in ; the molten state, and 0.1 to S.0 parts by weight of a ; crystalline seed forming agent, discharging the resultant mixture in a molten state through a die 35 thereby producing a molten membrane in the form of a flat film, cooling and solidifying the molten membrane by contact with a cooling and solidifying liquid exhibiting no compatibility to the organic filler and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g, and then bringing the cooled and S solidified membrane into contact with an extractant incapable of dissolving the polypropylene and capable of dissolving the organic filler thereby removing the organic filler from the membrane by extraction.
This invention also discloses a method for the 10 production of a flat-fim porous polypropylene membrane, wherein the porous polypropylene membrane obtained after the aforementioned removal of the organic filler by extraction is fixed in a presciribed length is subjected to a heat treatment at a temperature in the ranye of ` 15 110 to 140C. This invention further discloses a method for the production of a flat-film type porous polypropylene membrane, wherein the contact of the molten membrane with the cooling and solidifying is effected by disposing a guide roller in the cooling and 20 soldifying liquid, allowing part of the guide roller to emerge from the surface of the cooling and solidlfying liquid, discharging the aforementioned mixture onto the guide roller,~ and allowing the mixture to be led into the cooling and solidifying liquid by the rotation of 25 the guide roller. Further this invention discloses a method for the production of a flat-film type porous polypropylene membrane, wherein the cooling and solidifying liquid is a polyether. This invention also discloses a method for the production of a flat-film 30 type porous polypropylene membrane, whrein the polypropylene is a polypropylene possessing a melt index in the range of 5 to 40 and having mixed therewith 0 to 50% by weight of a polypropylene possessing a melt index in the range of 0.0~ to 5. This invention also 35 discloses a method ~or the production of a flat-film type porous polypropylene membrane, wherein the ~ 3 ~
crystalline seed forming agent is incorporated therein in an amount in the range of 0.1 to l.0 part by weight.
This invention further discloses a method for the production of a flat-film type porous polypropylene 5 membrane, wherein the crystalling seed forming agent is an organic heat-resistant substance possessing a melting point of not less than 150C and a gelling point of not less than the crystallization startin~ point o~ the polypropylene. Further, this invention discloses a lO method for the production of a flat-film type porous polypropylene membrane, wherein the extractant is a halogenated hydrocarbon or a mixture of the halogenated hydrocarbon with a'ketone.
[Brief Description of the Drawinys]
Fig. 1 is a schematic diagram illustrating a typical apparatus to be used in working the method of production of flat-film type porous polypropylene membrane of this invention. Fi~. 2 is a circuit diagram for the measurement of the highest blood plasma 20 separtion speed~ Figs. 3 and ~ are electron microscope photographs illustrating textures of typical flat-film type porous polypropylene membranes of the present invention. Figs. 5 and 6 are electron microscope photographs illustrating textures of flat-film-type 25 porous membranes used for comparative experiments. Fig.
7 is a graph showi,ng the relation between the blood plasma separatin speed (Qf) and the total membrane pressure (T.M.P.). Fig. 8 is a graph showing the relating between the total membrane pressure and the 30 amount of free hemoglobin (~Hb). Fig. 9 a through c illustrate realtions of permeation of various components of blood plasma vs the blood plasma separatin speed (Qf). Figs. 7 through 9 illustrate the data of Example l with blank cycles (O ) and the data of Control l with 35 solid circles (~).
~Description of Preferred Embodiments]
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~ ow, the present invention will be described below with reference to working examples. To ~acilitate comprehension of this invention, paragraphs titled "Flat-Film Type Porous Polypropylene Membxane," "Method 5 for the Production of Flat-Film Type Porous Polypropylene Membrane," and "Example" will he included in the following part of the text hereof.
Flat-Film Type Porous Polypropylene ~embrane The flat-film type porous polypropylene 10 membrane of the present invention i5 a flat-film type porous membrane formed substantialy with polypropylene in a wall thickness in the range of 30 to 300 ~m, preferably 60 to 200 ~m. The microstructure of this flat-film tyep porous polypropylene membrane is variable !,~ 15 with the conditions for production of the porous membrane. Generally, however, it is enabled to acquire such a st~ucture as shown by the photographs of Figs. 3 and 4 taken under a scanning electron micrograph by using, as a cooling and solidifying liquid to be fully 20 described later, a solution exhibiting no compatibility with the~organic filler and possessing specific heat capacity in the range of 0.2 to 0.7 cal/g.
Specifically, the flat-film type porous polypropylene `membrane of this insvention possesses a microreticular 25 structure which is formed with interlaces threads each consisting of interconnected particles of polypropylene.
In either or both of the opposite surface parts of the membrane, a surface layer of practically the same microreticular structure as in the interior of the 30 membrane is formed. The flat-film type porous polypropylene membrane of this invention possesses pores such that the pores in the interior thereof have the same diameter as those in the porous membrane obtained by using paraffin as the cooling and solidifying liquid 35 (Figs. 5 and 6) and the pores in the surface parts thereof, unlike those in the porous membrane using ~ !
paraffin as the cooling and solidifying liquid, have roughly the same diameter as those in the interior of the membrane. Surprisingly, it has been found that the flat-film type porous polypropylene membrane of this 5 invention which possesses such a microstructure as described above exhibits as high permeation speed and separation ability as the porous membrane obtained by using paraffin, for example, as the cooling and solidifying liquid and has a very remote possibility of 10 inducing occlusion of blood cells or hemolysis in consequence of contact with blood.
In the flat-film type porous polypropylene membrane of the present invention, the pores formed therein are desired to have an average diameter in the 15 range of 0.1 to 5.0 ~m, preferably 0.2 to 3.0 ~m. If the average pore diameter is less than O.l~m, the membrane is liable to exhibit an insufficient permeation speed to the blood plasma and the pores are liable to be clogged. Conversely, if the average pore diameter 20 exceeds 5.0 ~m, the porous membrane has the possibility of permitting not only the blood plasma component but also the blood cell component (erythrocytes leukocytes, and platelets) to permeate therethrough. So long as the average pore diameter f~lls in the aforementioned range, 25 the porous membrane is capable of passing not less than 95% of the total protains, namely the blood plasma component, without passing the blood cell component.
The texm l'average pore diameter" as used herein means the average diameter of all the pores contained 30 throughout the entire volume of the membrane as actually mesured with a mercury porosimeter and not the average diameter of the pores contained only in the surface layers. In the flat-film type porous polypropylene membrane of the present invention, the bubble point is 35 required not to exceed 2.0 kgf/cm2, preferably 1~8 kgf/cm2. ~he term "bubble ~oint" as used herein means ~L 3 ~
to define the largest allowable pore diameter of the membrane. If the bubble point exceeds 2.0 kgf/cm2, the pores in the membrane have too small diameters for the porous membrane to fit speedy filtration of blood plasma 5 and exhibit sufficient permeability to the blood plasma component.
Further, in the flat-film type porous polypropylene membrane of the present invention, the porosity is in the range of 60 to 85%. If the porosity 10 is less than 60%, the poxous membrane is liable to exhibit insufficient permeability and offer no sufficient blood plasma separation speed. Conversely, if the porosity exceeds 85%, the porous membrane to be produced is liable to acquire no sufficient working : 15 strength. Further in the flat-film type porous polypropylene membrane of the present invention, the amount of water to be passed therethrough is required to exceed 100 ml/min.mmHg.cm , preferably 140 ml/min.mmHg.cm . If the amount of water passed 20 therethrough is less than lOOml/min~mmHg.cm2, the porous membrane is liable to offer no sufficient blood plasma seapration speed. The flat-film type porous polypropylene membrane of this invention is required to `have a waLl thickness in the range of 30 to 300 ~m. If 25 the wall thickness is less than 30~m, the porous membrane is liable to be deficient in strength.
conversely, if the wall thickness exceeds 300~m, the module to be obtained by incorporating a multiplicity of such porous membranes is liable to occupy too large a 30 volume ot suit practical use.
The shrinkage which the flat-film type porous polypropylene membrane of this in~ention exhibits after 120 minutes' heat treatment at 121C is required not to exceed 6.0~, preferably 3,0%. The expression "120 35 minutes' heat treatment at 121C" represents the high-pressure steam sterilization specified by the .
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Japanese Pharmacopoeia. The term "shrinkage" as used herein means the degree of change in amount of the porous membrane before and after the aforementioned heat treatment. Since the flat-film type porous 5 polypropylene membrane of the present invention is a flat film in shape, the foregoing requirement dictates that the change to be brought abut by the heat treatment in the length of the porous membrane in the dirction perpendicular to the axis of molding should be not more 10 than 6.0%. If the shrinkage exceeds 6.0%, the porous memebrane is liable to offer no sufficient separation of the blood component because of decrease in the amount of water to be passed and decrease in the blood plasma separation speed.
15Method for Production of Flat-Film type Porous Polypropylene Membrane The flat-film type porous polyrpopylene membrane of the present invention which possesses the characteristic properties described above is produced, 20 for example, as follows.
As illustrated in Fig. 1, a composition 111 consisting of polypropylene, an organic filler, and a crystalline seed forming agent is fed through a hopper ` 112 to a mi~er such as, for example, a twin-screw 25 extruder 113 to be melted and blended therein and extruded therefrom, forwarded to a T die 114, discharged in the form of a flat film therefrom, brought down toward a guide roller 116 disposed inside a cooling tank 115 holding therein a cooling and solidifyin liquid 117 30 and allowed to contact the guide roller 116 at a Ievel higher than the surface of the cooling and solidifying liquid 117, and then led into the cooling and solidifying liquid 117 by the rotation of the guide roller 116. In this embodiment, the contact of the 35 molten membrane with the cooling and solidiying liquid is effecte by use of the guide roller. Optionally, the molten membrane may be dischargea directly into the cooing and solidifying liquid instead. The molten membrane is completely cooled and solidified while it is travelling through the interior o~ the cooing tank 115 5 and then taken up on a ta~eup roller 118. In this while, the cooling and solidifying liquid 117 which is supplied via a line 119 is discharged via a line 120, then cooled to a prescribed temperature by a cooling device (such as, for example, a heat exchanger) 121, and 10 recycled. The membrane taken up as described above was then led into an extraction tank (not shown) filled with an extractant, there to be deprived of the organic filler by extraction. The membrane emanating from the extraction tank, when necessary, is subjected to 15 re-extraction, drying, and heat treatment, for example, before it is rewound. For the purpose of stabilizing the construction and the permeation property of the porous membrane to be produced the membrane is desired to be subjected to the heat treatment as fixed in a 20 prescribed length. The extraction of the organic filler from the membrane may be effected by the use of an extractin tank disposed before the step of the rewinding.
The polypropylne to be used as one of the raw 25 materials in the method of this invention need not be limited to homopol~ymer of propylene. It may be a block copolymer using propylene as the main component and additionally incorporating therein another monomer (such as, for example, polyethylene). Desirably, the 30 polypropylene is required to possess a melt index (M.I~) in the range of 5 to 70, preferably 10 to 40. Fuxther for the purpose of enhancing the strength of the membrane, the polypropylene to be used in the composition is desired to have a large molecular weight, 35 namely, a low M.I. Fox example, a mixture consisting of a species of polypropylene having a M.I. in the range of ;
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0.05 to 5 is used to advanrage. In all the species of polypropylene enumerated above, the homopolymer of propylene proves to be particulaxly advantageous, especially so where the homopolymer possesses high 5 crystallinity.
The organic filler is required to be uniformly dispersible in the polypropylene which is in a molten state and to be easily soluble in an extractant to be used later. Examples of the filler which fulfils this 10 requirement include liquid paraffin (number average molecular weight 100 to 2,000), ~ -olefin oligomers [such as, for example, ethylene oligomer (number average molecular weight 100 to ~,000), propylene oligomer (number average weight 100 to 2,000), and ethylene 15 oligomer (number average molecular weight 100 to 2,000)], paraffin wax (number average molecular weight 200 to 2,500), and various hydrocarbons. On the organic fillers enumerated above, the liquid paraffin proves to be particularly desirable.
The mixing ratio of the polyrpopylene and the aforementioned organic filler is such that the proportin of the organic filler to 100 part~ by weight of the propylene is in the range of 200 to 600 parts by weight, peferably 300 to 500 parts by weight. I fhte proportion 25 of the organic filler is less than 200 parts by weight, the flat~ilm typè porous polypropylene membrane to be produced possesses unduly low porosity and water permeability and fails to acquire sufficient permeation property. If this proportion exceeds 600 parts by 30 weight, the produced membrane exhibits unduly low viscosity and deficiency in workability. For the formulation of raw materials mentioned aboe, the mixture consisting of raw materials in a prescribed percentage composition is prepared (designed) by the premix method 35 which comprises melting and blending the mixture, -: ~
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extruding the resultant blend, and pelletizing the extruded blend by the use of biaxial type extruding machine, for example.
The crystalline seed forming agent to be 5 included in the raw materials for this invention is an organic heat-resistant substance possessing melting point of not less than 150C, preferably in the range of 200 to 250C, and a gelling point of not less than the crystallization starting piont of polyolefin~ The 10 crstalline seed forming agent of this description is used as one of the raw materials for the purpose causing contraction of the particles of polypropylene thereby controlling the gap b~tween the solid phases, namely the diameter of micropores to be formed. As examples of the lS crystalline seed forming agent, there can be cited 1,3,2,4-dibenzilyaene sorbitol, 1,3,2,4-bis(p-methylbenzilydene~ sorbitol, 1,3,2,4-bis(p-ethylbenzilydene)sorbitol, bis(4-t-butylphenyl)sodium phosphate, sodium benzoate, 20 adipic acid, talc and kaoline. Among other crystalline seed forming agents enuemxated above, 1,3,2,4-dibenzylidene sorbitol, 1,3,2,4-bis(p-ethylbenzilydene) sorbitol, and 1,3,2,4-bis(p-methylbenzylidene) sorbitol prove to be 25 advantageous because they do not appreciably dissolve out into the blood.
The mixing ratio of the propylene and the aforementioned crystalline seed forming agent is such that the proportion of the crstalline seed forming agent 30 to 100 parts by weight of the polypropylene i5 in the range of 0.1 to 5 parts by weight, preferably 0.2 to 1.0 part by weight.
As the cooling and solidifying liquid for this invention a solution exhibiting no compatibility with 35 the organic filler being used and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g, , ~
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'J~ ~3 preferably 0.3 to 0.6 cal/g. As concrete e~amples of the cooling and solidifying liquid, there can be cited polyethers such as polyethylene glycol and water-soluble paraffins which are insoluble in the oragnic filler.
5 Among other cooling and solidifying liquids enumerated above, various species of polyethylene glycol prove to be particularly advanrageous, especially so when their average molecular weights fall in the range of 100 to 400. The species of polyethylene glycol possessing an 10 average molecular weight in the range o~ 18~ to 330 proves to be the most desirable selection. Such a liquid as exhibiting no compatibility with the organic filler being used and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g is used as the - 15 cooling and solidifying liquid for the following reason.
When a compound identical or similar to the aforementioned organic filler is used as the cooling and solidifying liquid, namely when a species of liquid paraffin is used as the organic filler and another 20 species of liquid paraffin possessing number average molecular weight approximating that of the first species of li~uid paraffin is used as the cooling and solidifying liquid, the produced membrane is enabled to contain pores in a prescribed density without entailing 25 any appreciable migration of the organic filler in the molten membrane. Further, since the specific heat is not unduly large, the polypropylene is crystallized smoothly at a proper cooling speed to form particles stably. During the course of this cooling, the 30 polypropylene dissolves out into the cooling and solidifying liquid before the polypropylene in the surface parts is solidified. As the result, a very large reticular structure is formed in the surface parts. When an inactive liquid exhibiting no 35 compatibility with the organic filler and possessing a large specific heat capacity of about 1.0 cal/g, is used ,~
as the cooling and solidifying liquid, the polypropylene is quickly cooled, the phase separation between the polypropylene is qulckly cooled the phase separation between the polypropylene does not suffciently proceed, 5 and the pores in the surface parts and those in the interior of the membrane are both small and the porosity of the membrane is 1ow becaue the cooling effect of the liquid is high.
In contast, when a liquid exhibiting no 10 compatibility with the aforementioned organic filler and possesisng a specific heat capacity in the range of 0.2 to 0.7 cal/g is used as the cooling and solidifyng liquid, the propylene is not suffered to dissolve out in the surface parts, the cooling speed of the t 15 polypropylene is proper, and the polypropylene is smoothly crstallized even in the surface parts with the composition ratio thereof retained intact. As the result, there can be formed a reticular structure which is not enlarged unduly even in the surface parts and 20 which is enabled to contain amply large pores fit for blood plasma separation even within the interior thereof.
The temperature of the cooling and solidifying liquid is desired to be in the range of 10 to 80C, 25 preferably 30 to 60C, for the following reason~ If this temperature is less than 10C, since ~the cooling and solidifying speed is so fast that the micropores to be formed consequently have a very small diameter.
Conversely, if the temperature exceeds 80C, the cooling 30 and solidifying treatment does not proceed amply and the molten emmbrane is liable to break in the cooling and solidifying liquid.
The membrane which has been throughly cooled and solidified in the cooling and solidifying tank is 35 brought into contact with the extractant to permit removal of the organic filler therefrom by extraction.
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This solution and extraction of the organic filler may be effected by the extraction tank method or the shower method which comprises advanting the membrane on a belt conveyor and causing the extractant to fall in the form 5 of shower OlltO the membrane in motion.
As the extractant, any liquid can be used on the sole condition that it should be incapable of dissolving the polypropylene forming the backbone of the porous membrane and acapable of dissolving and 10 extracting the organic filler. Examples of the liquid answering the description include such halogenated hydrocarbons as tetrachloromethane, 1,1,2-trichloro-1,2,2-trifluoroethane, trichlorofluoromethane, dichlorofuluoromethane, 15 1,1,2,2-tetrachloro-1,2-difluoroethane, trichloroethylene, and perchloroethylene. In the liquids enumerated above, chlorofluorinated hydrocarbons prove to be desirable in terms of ability to extract the organic filler and safety in the human system. Where a 20 sorbitol is used as the crystalline seed forming agent, a ketone may be incorporated in the extractant so as to remove the sorbitol from the porous membrane during the course of extraction and thereby to preclude the otherwise possible exudation of the sorbitol from the 25 surface of the porous membrane after the molding.
The falt-film type porous polypropylene membrane which is obtained as described above, when ; necessary, may be further subjected to a heat treatment.
; This heat treatment is carried out at a temperature 10 30 to 15C lower than the melting point of the polypropylene, specifically a temperature in the range of 110 to 150C, preferably 130 to 140C, for a period in the ragnge of 30 to 180 secondst prefarably 60 to ~0 seconds. Preparatory to the heat treatment, the porous 35 membrane must be fixed in a prescribed length. ~he flat-film type porou polypropylene membrane which is ~ 3 ~
produced as described above is useful as a membrane for the separation of blood into blood cells and blood plasma and as a microfiler for the removal of bacteria from blood. It is used particularly advantageously as a 5 membrane for the separation of blood plasma where the separted blood plasma is put to use as in the treatment of donorpheresis.
Example As an aid for further facilitating the 10 comprehension of this invention, a few working exampls will be cited below. There exampls are offered purely for the purpose of illustrating this invention and are not meant to restrict the scope of this in~netion in any respect.
15 Examples 1 through 3 and Controls 1 through 3:
By the use of a twin-screw extruder (produce dby Ikegai Iron Works, Ltd. and marketed under trademark designation of PCM-30-25), 100 parts by weight of a mixture of two polypropylne species possessing melt flow 20 indexes of 30 and 0.3 (mixing ratio 100 : 40 by weight), varying proportions of liquid paraffin (nul~er average molecular weight 324), and 1,3,2,~-bis(p-ethylbenzylidene)sorbitol as a crystalline seed forming agent indicated in Table 10 were melted and 25 kneaded and pelletized. By the aforementioned extruder, the pellets were melted at a varying temperature in the range of 150 to 200C, extruded through a T die 0.6 mm in slit width into the air, allowed to fall onto a guide roller in a colling liquid tank disposed directly below 30 the T die, led into the cooling and solidifying liquid by the rotation of the roller to be cooled and solidified therein, and thereafter taken up. The kind and temperature of the cooling and solidifying liquid used in this case were as shown in Table 1. From the 35 film thus taken up, a square (about 200 x 200 mm) was cut off, fixed in both the longitudinal and lateral ,:
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directions, immersed four times in 1,1,2-trichlor-1,2,2-trifluoroethane (liquid temeprature 25C) for 10 rninutes each to effect expulsion of the liquid para~fin, and then heat trea-ted 5 in the air at 135C ~or 2 minutes.
The flat-film type porous polypropylne membrane consequently obtained was tested for wall thickness, bubble point, porosity, water permeation, and highest blood plasma separation speed~ The results are 10 shown in Table 1.
Then, to determined the microstructure of the flat-film type porous polypropylene membrane, various portions of the membrane were observed under a scanning electron microscope (produced by JEOL and marketed under 15 product code of "JSM-840"~. Fig. 3 is a photomicrograph of the surface (x 1,000) of the flat-film type porous polyrpopylene membrane of Example 1, Fiy. 4 of the partial cross section (x 2,500) of the flat-film type prous polypropylene membrane of Example 1, Fig. 5 of the 20 surface (x 1,000) the flat-film type porous polypropylene membrane of Control 1, and Fig. 6 of the partial cross section (x 3,000) of the flat-film type porous polypropylene membrane of Control 1, respectively taken under the electron microscope. It is clearly 25 noted from Fig. 3, and Fig. 4 that the flat-film type porous polypropylene membrane of Exmaple I according with the present invention possessed practically equal reticular structure in the surface parts and in the interior of the membrane, the surface layers had a 30 virtually negligible thickness (about 0.5~ of the total membrane thickness), and the reticular structure had attained full development even in the interior of the membrane. In contrast t the flat-film type porous polypropylene membrane obtained by used liquid paraffin 35 as the cooling and solidifying liquid (control 1), as clearly noted from Fig. 5 and Fig. 6, possessed as fully trade-marlc ~. 3 ~
developed A reticular structure in the interior of the membrane as in the membrane of E~maple 1, possessed fairly rough reticular s-tructure in the surface paxts, and had surface layers of a fairly large -thickness 5 (about 24.0% of the total thickness of the membrane).
The comparison offers a definite evidence that the falt-film type porous polypropylene membrne of Example l according with the present invention ~uffered sparingly from occulsion of blood cells~
Separately, life-size laminate modules severally incorporateing therein the falt-film type porous polypropylene memebrane of E~ample l and Control l were operated t~ effect blood plasma separation of bovine blood, to compare the flat-fim type porous 15 polypropylene membrane in ability o~ blood plasma separation. Results are shown in Fig. 7 - 9. Fig. 7 shows the relation between the speed of blood plasma separation (Qf) and the total intermembranous pressure (T.M.P.) and Fig. 8 the relation between the T.M.P~ and 20 the amount of free hemoglobin ( ~ Hb).
Control 4:
For the purpoe of comparison, a commercially availabel cellulose acetate membrane (C~; produced by Toyo Filter Paper Co., ltd.) was similarly tested for 25 thickness of membrane, bubble point, porosity, water permeation, and highest blood plasma separation speed.
The results are shown in Table l.
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aJ S --1 CJ ~.,1 E~ O
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a) O : : .1N `1 C: ~1 ~1 O O ,,1 ~r-l N ,.
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It is clearly noted from Table 1 that the flat-film type porous polypropylene membranes of the present invention (Examples 1 through 3) exhibited high porosity and water permeability and also possessed high 5 blood plasma separation speeed.
Further the flat-film type porous polypropylene membranes of this invention, owing to their membranous structure, suffered sparingly from occlusion of blood cells and they had an advatnage of 10 hardly admitting of hemolysis as shown in Figs. 7 and 8.
In contrast, the flat-film type porous polypropylene membranes of Conotrols 1 through 3 which used liquid paraffin or halo~enated hydrocarbon as the cooling liquid were liable to induce hemolysis and ocnsequently : 15 were not allowed to use any large intermembranous pressure, thouyh they exhibited as high blood plasma eparation speed as the flat-film type porous polypropylene membranes of the present in~ention. In terms of the permeability to the componenets of blood 20 plasma, the flat-film type porous polypropylene membrane of this invention (Example 3~ was favorably comparable with that of Control 1 which had a large surface pore - diameter.
The various terms used in the present 25 specification concerning the Flat-film tyep porous polypropylene membrane and the methods used for the determination of the properties mentioned herein are - de~iend below.
Bubble point This property was determined in accordance with the method of correction specified in ASTM F316, using a stainless steel holder 47 mm in diameter and -~ isopropyl alcohol as a liquid alcohol. The pressure applied was continuously increased until a continuous 35 line of nitrogen bubbles began to rise uniformly and ' . .
. ~
.
.~
~ ~ 3~
incessantly from the center of the filter through the isopropyl alcohol. The pressure at this point was reported as bubble point.
Thickness of membrane This property was determined by actually measuring the thickness of a given membrane with the aid of micrometer.
Porosity ~ ~ . . . = _ A given flat-film type porous polypropylene 10 membrane was immersed in ethanol and then hydrated by means of displacement of ethanol with wa-ter and the weight of the water (Wp) conse~uently contained therein was determined. The porosity was calculated in accordance with the fol.lowlng formula:
(Wp-Ww) x 100 (Ww/P) + (Wp-Ww) wherein Ww stands for the weight of the membrane in the dry state and P g/ml for the density of the polymer.
Water permeation .
Water at 25C was caused to permeate a give membrane measuring 1.45 x 10 3 m2 in area under application of a pressure of 0.7 kgf/cm2. The -time required for 100 ml of water to pass through the membrane was clocked and reported as water pemation.
25 Highest blood pLasma separation speed (Qf max) This property was determined by use of a circuit illustrated in Fig. 2. In a module 30 possessing a membrane surface area of 0.4 m2~ fresh bovine blood incorporating therein heparin of a 30 hematocrit value of 40~ (5,000 U/liter) was circulated in a flow volume of lOOml/min at a pressure loss of 30 mmHg, with the flow volume of filtration pump successively increased from 10 ml/min to 10, 15, 20, 25, 30, 40, and 42 at intervals of 30 minutes. The amount .
;' 6 ~
of filtrate immediately before the increase o~ T~M.P.
within an interval of 30 minutes surpassed 20 mmHg was found and reported as Qf max.
in + POut/2 - Pfil is presumed.
5 In ~ig. 2, Gl, G2, and G3 each denote a pressure meter, the pressure of Gl is expressed as Pin, that of Ga as Pfil, and that of G3 as PoUt respectively, Every P
indicated in the diagram stands for a pump.
Average pore diameter This property was determined by actually measuring the size of pores, in a given membrane with a mercury porosity.
~Industrial Utility of the Invention~
As described above, this invention concerns a 15 flat-film type porous polypropylene membrane possessing a microreticular structure, characterized by the fact that either or both of the opposite surface region of the porous membrane forms a surface layer possessing an average pore diameter in the range of 0.1 to 5.0~m, a 20 bubble point of not more than 2.0 kgf/cm2, a porosity in the range of 60 to 85%, and a water permeability of not less than 100 ml/min.mmHg.m2, and the mem~rane possesses a wall thickness in the range of 30 to 300~m. Thus, the flat-film type porous polypropylene membrane exhibits 25 high porosity and water permeability. When it is used for blood plasma separation, it suffers sparinyly from clogging of pores with proteins or blood cells, effects separation of blood plasma at a high speed, and entails only slight occlusion of blood cells and hardly includes 30 hemolysis. Owing to these features, the falt-film type porous polypropylene membrane is used advantageously for blood plasma separation, i.e. the separtion of blood into blooa cells and blood plasma~. It is particularly useful as a membrane for bloood plasma separation where 35 the separated blood plasma is put to use as in the donorpheresis. The flat-film type porous polypropylene -~4-`:"
' ' ' ' ' ~
' . . ' ' ~ 3 ~
membrane of this invention is enabled to manifest these highly desirable properties still more to advantage when the bubble point is not more than 1.8 kgf/cm2, the water permeation not less than 140ml/min.mmHg.m2, and the 5 ratio of shrinkage due to 120 minutes' heat treatment at 121C is not more than 6.0%.
This invention also concerns a method for the production of a flat-film type porous polypropylene membrane, characterized by mixing 100 parts by weight of 10 polypropylene, 200 to 600 parts by weight of an organic ~iller uniformly dispersible in the polypropylene in the molten state, and 0.1 to 5.0 parts by weight of a crystalline seed ~orming agent, discharging the resultant mixture in a molten state through a die 15 thereby producing a molten membrane in the form of a flat film, cooling and solidifying liquid exhibiting no compatibility to the organic filler and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g, and then bringing the cooled and solidified membrane 20 into contact with an extractant incapable of dissolving the polypropylene and capable of dissolving the organic filler thereby removing the organic filler form the membrane by extraction. This method is capalbe of easily producing the flat-film type porous polypropylene 25 membrane possessing the aforementioned outstanding properties. The properties of the flat-film type porous polypropylene membrane are stabilized to a greated extent when the method described above further comprises ; causing the flat-film type porous polypropylene membrane 30 which results from the removal of the organic filler by extraction to be fixed in a prescribed length and subjected to a heat treatment at a temperature in the range of 110 to 140C. The flat-film type poxous polypropylene membrane o~ high grade can be obtained 35 easily when the contact of the molten membrane with the cooling and solidifying liquid is effected by having a .
11 3 ~ 3 1~
guide roller disposed in the cooling and solidfying liquid, discharging the molten mix~ure onto the guide roller, and causing the molten mixture to be led into the cooilng and solidifying liquid by the rotation of 5 the guide roller. The properties of te flat-film type porous polypropylene membrane are further enhanced when the cooling and solidifying liquid is a polyether, the polypropylene consists of a species of polypropylene possessing a melt index in the range of 5 to 40 and 0 to 10 50% by weight of another species of polypropylene possessing a melt index in the range of 0.05 to 5, the crystalline seed forming agent is incorporated in the mixtrue in a proportion falling in the range of 0.2 to 1.0 part by eight, the crystalline seed forminng agent -~. 15 is an organic heat-resistant substance possessing melting point of not less than 150C and a gelling point not less than the crystallization starting point of polypropylene, and the extractant is either a halogenated hydrocarbon or a mixtue of a halogenated 20 hydrocarbon with a ketone.
SPEC IFICATION
POROUS POLYPROPYLENE MEMB~ANE ~ND METHOD
FOR PRODUCTION THEREOF
BACKGROUND OF ~HE INVENTION
5 tFiled of the Invnetion]
This invention relates to a porous polypropylene membrane and a method for the production thereof. This invention also relates to a flat film type porous polypropylene membrane to be used for blood 10 plasma separation, i.e. separation of blood into blood cells and blood plasma, and for removal of bacteria from blood and a method for the production thereof. More particularly, this invention relates to a flat-film type porous polypropylene membrane which, when used for the 15 blood plasma separation, exhibits a high blood plasma separa-tion speed and has only a sparing possibility of incurring such adverse phenomena as leakage of part of the blood cells in the blood plasma after the blood-plasma separation and hemolysis and a method for 20 the production thereof.
[Description of the Prior Art]
Heretofore, vrious permeable membranes have been adopted for the purpose of separating blood into blood cells and blood plasma. These permeable membranes 25 are used for blooa plasma purification aimed at removal of abnormal protei~s, antigens, antibodies, and immune complexes in such diseases due to abnormal immunity as systemic lupus erythematosus, rheumatoid arthritis, glomerular nephritis, and myasthenia gravis, for 30 manufacture of blood plasma preparations for component transfusion, and for pretreatment of artificial kidneys, for example. As examples of the permeable membranes heretofore used for the blood plasma separation mentioned above, there can be cited a cellulose acetate 35 membrane (applicant's Japanese patent Unexamined Publication SHO 54(1979)-15,476, publishe~ February 5, 1979) and a polyvinyl alcohol membrane, a '.
~. 3 11 ~
polyester membrane, a polycarbonate membrane, a polymethyl methacrylate membrane, and a polyethylene membrane (applicant's Japanese Patent Unexamined Publication SH0 57(1982)-84,702, published May 27, 1982).
5 These parmeable membranes are deficient in mechanical strength, porosity, and plasma separating ability. When these permeable membranes are used in the blood plasma separation, owlng to the clogging of the micropores therein, the erythrocytes lO are injured and the components of complement in the blood plasma are activated and the separated blood plasma is seriously injured as the result.
A permeable membrane has been proposed which is produced by mixing a polymer such as a crystalline 15 polyolefin or polyamide which is sparingly soluble in a solvent and is stretchable and a compound partially compatible wi-th the polymer and readily soluble in the so]vent, molding the resultant mixture in the form of film, sheet, or a hollow article, treating the shaped 20 article with the solvent, drying the treated shaped article, and then uniaxially or biaxially stretching the dried shaped article to an extent fallng in the range of 50 to 15,000% (applicant's Japanese Pa~ent Publication SHO
57~1982)-20,970, published May 4, 1982). Since this 25 membrane has been stretched for the purpose o~ increasing pore diameter, it is susceptible of thermal shrinkage so much that, when the permeable membrane is used in a medical device, it will not be ab]e to be safely sterilized in an 30 autoclave. Moreover since the micropores are formed by stretching in the permeable membrane, they are linear micropores substantially parallel to the direction of thickness of the membrane. Since the micropores have a substantially uniform shape in the opposite surfaces and 35 in the interior of the wall of the membrane, they are inevitably clogged with proteins and blood cells when the permeable membrane is used in the blood plasma separation.
_~ -2-., .
11 3~6~
As concerns permeable membranes for use in the blood plasma separation, polyolefin type macromolecules hav~ been attracting attention as materials experiencing activation of complements only to a nominal extent and 5 e~celling in bio-adaptability. At present, studies are underway on the feasibility of permeable membranes using such polyolefin type macromolecules. For example, there has been discloses a method for the produc-tion of a porous membrane, which comprises preparing a molten lO mixture consisting of lO to 80% by weight of a paraffin and 90 to 20% by weight of a polypropylene resin, extruding the molten mixture through a die in the form of a film, a sheet, or a hollow fi.ber, suddenly solidifying the molten extruded mixture in water kept at 15 a temperature of not more than 50C, and then separating the paraffin from the shaped article by extraction (applicant's Japanese Patent Unxamined Publication SHO
55(1980)-60,537, published May 7, 1980). The porous membrane which is obtained 20 by this method, however, cloes not fit speedy blood plasma separation because the membrane has been suddenly cooled with water, a substance of a large specific heat, and, as the natural consequence, the pores formed in the surfaces and those formed in the interior of the 25 membrane have small diameters and the porosity is low and the speed of permeation is proportionately low.
As means of cooling and solidlfying the aforementioned molten mixture, there have been proposed a method which uses a metallic roller and a method which 30 uses a cooling and solidifying liquid such as a paraffin possessing highly desirable compatibility with the aforementioned organic filler (ap~licant's Japanese Patent Application SH0 60(1985)-237,069 corresponding to Japanese Patent Unexamined' Publication SHO 62(1987)-97,603, 35 published May 7, 1987). The former method produces a porous membrane which possesses surface pores of an extremely small diameter and, therefore, passes blood plasma only at a low speed. In the latter method, since the cooling and so].idifying liquid has a small , 1 3 ~
specific heat as compared with water and, therefore, promotes the crystallization of polypropylene at a proper cooling rate, the membrane is enabled in the interior thereof to form micropores of a large diameter 5 enough for the purpose of blood plasma separation and is suffered in the surface regions thereof to form a very large reticular structure which is believed to arise becaue the polypropylene in the surface regions is dissolved out into the cooling and solidifying liquid 10 before it is allowed to solidify. In the porous membrane possessing such surface layers as described above, the surface layers each function as a prefilter.
Thus, the porous membrane is capable of carrying out the blood plasma separation at a highly desirable speed 15 without surffering proteins and blood cells to clog the micropores. When this porous membrane is brought into contact with blood, however, it is liable to occlude blood cells, which may possibly be forced to liberate homoglobin under application of pressure.
An object of this invention, therefore, is to provide an improved porous polypropylene membrane and a method for the production thereof. ~nother object of this invention is to provide an improved flat-film type porous polypropylene membrane and a method for the 25 production thereof. A further object of this invention is to provide a flat-film type porous polypropylene membrane to be used for blood plasma separation aimed at separting blood into blood cells and blood plasma and for removal of bacteria from blood and a method for the 30 production thereof. Yet another object of this invention is to provide a flat-film type porous polypropylene membrane which, while being used for blood plasma separation, permits the blood plasma separation to proceed at a high speed, suffers the separated blood .
.: :
: : :
plasma to be injured only sparinglyr and has little possihility of entailing occlusion of blood cells or hemolysis and a methocl for the production thereof.
[Deisclosure of the Invention]
The objects described above are accomplished by a flat-film type porous polypropylene membrane possessing a microreticular structure, characterized by the fact that either or both of the opposite surface region of the porous membrane forms a surace layer 10 possessing an average pore diameter in the range of 0.1 to 5.0~m, a bubble point of not more than 2.0 kgf/cm2, a porosity in the range of 60 to 85~, and a water permeability of not less than 100 ml/min.mmHg.m2 and the membrane posesses a wall thickiness in the range of 30 15 to 300~m.
This invention also discloses a flat-film type porous polypropylene membrane, wherein the bubble point of the membrane is not more than 1.8 kgf.cm~. This invention further discloses a flat-film type porous 20 polypropylene membrane, whrein the water permeability is not less than 140 ml/min.mmHg.m2. Further this invention discloses a flat-film type porous polypropylene membrane, wherein the shrinkage ratio after 120 minutes' heat treatment at 121C is not more 25 than 6.0~.
The object descrbied above are further accomplished by a method for the production of a flat-film type porous polypropylene membrane, chaxacterized by mixing 100 parts by weight of 30 polypropylene, 200 to 600 parts by weight of an organic filler uniformly dispersible in the polyperopylene in ; the molten state, and 0.1 to S.0 parts by weight of a ; crystalline seed forming agent, discharging the resultant mixture in a molten state through a die 35 thereby producing a molten membrane in the form of a flat film, cooling and solidifying the molten membrane by contact with a cooling and solidifying liquid exhibiting no compatibility to the organic filler and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g, and then bringing the cooled and S solidified membrane into contact with an extractant incapable of dissolving the polypropylene and capable of dissolving the organic filler thereby removing the organic filler from the membrane by extraction.
This invention also discloses a method for the 10 production of a flat-fim porous polypropylene membrane, wherein the porous polypropylene membrane obtained after the aforementioned removal of the organic filler by extraction is fixed in a presciribed length is subjected to a heat treatment at a temperature in the ranye of ` 15 110 to 140C. This invention further discloses a method for the production of a flat-film type porous polypropylene membrane, wherein the contact of the molten membrane with the cooling and solidifying is effected by disposing a guide roller in the cooling and 20 soldifying liquid, allowing part of the guide roller to emerge from the surface of the cooling and solidlfying liquid, discharging the aforementioned mixture onto the guide roller,~ and allowing the mixture to be led into the cooling and solidifying liquid by the rotation of 25 the guide roller. Further this invention discloses a method for the production of a flat-film type porous polypropylene membrane, wherein the cooling and solidifying liquid is a polyether. This invention also discloses a method for the production of a flat-film 30 type porous polypropylene membrane, whrein the polypropylene is a polypropylene possessing a melt index in the range of 5 to 40 and having mixed therewith 0 to 50% by weight of a polypropylene possessing a melt index in the range of 0.0~ to 5. This invention also 35 discloses a method ~or the production of a flat-film type porous polypropylene membrane, wherein the ~ 3 ~
crystalline seed forming agent is incorporated therein in an amount in the range of 0.1 to l.0 part by weight.
This invention further discloses a method for the production of a flat-film type porous polypropylene 5 membrane, wherein the crystalling seed forming agent is an organic heat-resistant substance possessing a melting point of not less than 150C and a gelling point of not less than the crystallization startin~ point o~ the polypropylene. Further, this invention discloses a lO method for the production of a flat-film type porous polypropylene membrane, wherein the extractant is a halogenated hydrocarbon or a mixture of the halogenated hydrocarbon with a'ketone.
[Brief Description of the Drawinys]
Fig. 1 is a schematic diagram illustrating a typical apparatus to be used in working the method of production of flat-film type porous polypropylene membrane of this invention. Fi~. 2 is a circuit diagram for the measurement of the highest blood plasma 20 separtion speed~ Figs. 3 and ~ are electron microscope photographs illustrating textures of typical flat-film type porous polypropylene membranes of the present invention. Figs. 5 and 6 are electron microscope photographs illustrating textures of flat-film-type 25 porous membranes used for comparative experiments. Fig.
7 is a graph showi,ng the relation between the blood plasma separatin speed (Qf) and the total membrane pressure (T.M.P.). Fig. 8 is a graph showing the relating between the total membrane pressure and the 30 amount of free hemoglobin (~Hb). Fig. 9 a through c illustrate realtions of permeation of various components of blood plasma vs the blood plasma separatin speed (Qf). Figs. 7 through 9 illustrate the data of Example l with blank cycles (O ) and the data of Control l with 35 solid circles (~).
~Description of Preferred Embodiments]
~ 3 ~
~ ow, the present invention will be described below with reference to working examples. To ~acilitate comprehension of this invention, paragraphs titled "Flat-Film Type Porous Polypropylene Membxane," "Method 5 for the Production of Flat-Film Type Porous Polypropylene Membrane," and "Example" will he included in the following part of the text hereof.
Flat-Film Type Porous Polypropylene ~embrane The flat-film type porous polypropylene 10 membrane of the present invention i5 a flat-film type porous membrane formed substantialy with polypropylene in a wall thickness in the range of 30 to 300 ~m, preferably 60 to 200 ~m. The microstructure of this flat-film tyep porous polypropylene membrane is variable !,~ 15 with the conditions for production of the porous membrane. Generally, however, it is enabled to acquire such a st~ucture as shown by the photographs of Figs. 3 and 4 taken under a scanning electron micrograph by using, as a cooling and solidifying liquid to be fully 20 described later, a solution exhibiting no compatibility with the~organic filler and possessing specific heat capacity in the range of 0.2 to 0.7 cal/g.
Specifically, the flat-film type porous polypropylene `membrane of this insvention possesses a microreticular 25 structure which is formed with interlaces threads each consisting of interconnected particles of polypropylene.
In either or both of the opposite surface parts of the membrane, a surface layer of practically the same microreticular structure as in the interior of the 30 membrane is formed. The flat-film type porous polypropylene membrane of this invention possesses pores such that the pores in the interior thereof have the same diameter as those in the porous membrane obtained by using paraffin as the cooling and solidifying liquid 35 (Figs. 5 and 6) and the pores in the surface parts thereof, unlike those in the porous membrane using ~ !
paraffin as the cooling and solidifying liquid, have roughly the same diameter as those in the interior of the membrane. Surprisingly, it has been found that the flat-film type porous polypropylene membrane of this 5 invention which possesses such a microstructure as described above exhibits as high permeation speed and separation ability as the porous membrane obtained by using paraffin, for example, as the cooling and solidifying liquid and has a very remote possibility of 10 inducing occlusion of blood cells or hemolysis in consequence of contact with blood.
In the flat-film type porous polypropylene membrane of the present invention, the pores formed therein are desired to have an average diameter in the 15 range of 0.1 to 5.0 ~m, preferably 0.2 to 3.0 ~m. If the average pore diameter is less than O.l~m, the membrane is liable to exhibit an insufficient permeation speed to the blood plasma and the pores are liable to be clogged. Conversely, if the average pore diameter 20 exceeds 5.0 ~m, the porous membrane has the possibility of permitting not only the blood plasma component but also the blood cell component (erythrocytes leukocytes, and platelets) to permeate therethrough. So long as the average pore diameter f~lls in the aforementioned range, 25 the porous membrane is capable of passing not less than 95% of the total protains, namely the blood plasma component, without passing the blood cell component.
The texm l'average pore diameter" as used herein means the average diameter of all the pores contained 30 throughout the entire volume of the membrane as actually mesured with a mercury porosimeter and not the average diameter of the pores contained only in the surface layers. In the flat-film type porous polypropylene membrane of the present invention, the bubble point is 35 required not to exceed 2.0 kgf/cm2, preferably 1~8 kgf/cm2. ~he term "bubble ~oint" as used herein means ~L 3 ~
to define the largest allowable pore diameter of the membrane. If the bubble point exceeds 2.0 kgf/cm2, the pores in the membrane have too small diameters for the porous membrane to fit speedy filtration of blood plasma 5 and exhibit sufficient permeability to the blood plasma component.
Further, in the flat-film type porous polypropylene membrane of the present invention, the porosity is in the range of 60 to 85%. If the porosity 10 is less than 60%, the poxous membrane is liable to exhibit insufficient permeability and offer no sufficient blood plasma separation speed. Conversely, if the porosity exceeds 85%, the porous membrane to be produced is liable to acquire no sufficient working : 15 strength. Further in the flat-film type porous polypropylene membrane of the present invention, the amount of water to be passed therethrough is required to exceed 100 ml/min.mmHg.cm , preferably 140 ml/min.mmHg.cm . If the amount of water passed 20 therethrough is less than lOOml/min~mmHg.cm2, the porous membrane is liable to offer no sufficient blood plasma seapration speed. The flat-film type porous polypropylene membrane of this invention is required to `have a waLl thickness in the range of 30 to 300 ~m. If 25 the wall thickness is less than 30~m, the porous membrane is liable to be deficient in strength.
conversely, if the wall thickness exceeds 300~m, the module to be obtained by incorporating a multiplicity of such porous membranes is liable to occupy too large a 30 volume ot suit practical use.
The shrinkage which the flat-film type porous polypropylene membrane of this in~ention exhibits after 120 minutes' heat treatment at 121C is required not to exceed 6.0~, preferably 3,0%. The expression "120 35 minutes' heat treatment at 121C" represents the high-pressure steam sterilization specified by the .
~ 3 ~
Japanese Pharmacopoeia. The term "shrinkage" as used herein means the degree of change in amount of the porous membrane before and after the aforementioned heat treatment. Since the flat-film type porous 5 polypropylene membrane of the present invention is a flat film in shape, the foregoing requirement dictates that the change to be brought abut by the heat treatment in the length of the porous membrane in the dirction perpendicular to the axis of molding should be not more 10 than 6.0%. If the shrinkage exceeds 6.0%, the porous memebrane is liable to offer no sufficient separation of the blood component because of decrease in the amount of water to be passed and decrease in the blood plasma separation speed.
15Method for Production of Flat-Film type Porous Polypropylene Membrane The flat-film type porous polyrpopylene membrane of the present invention which possesses the characteristic properties described above is produced, 20 for example, as follows.
As illustrated in Fig. 1, a composition 111 consisting of polypropylene, an organic filler, and a crystalline seed forming agent is fed through a hopper ` 112 to a mi~er such as, for example, a twin-screw 25 extruder 113 to be melted and blended therein and extruded therefrom, forwarded to a T die 114, discharged in the form of a flat film therefrom, brought down toward a guide roller 116 disposed inside a cooling tank 115 holding therein a cooling and solidifyin liquid 117 30 and allowed to contact the guide roller 116 at a Ievel higher than the surface of the cooling and solidifying liquid 117, and then led into the cooling and solidifying liquid 117 by the rotation of the guide roller 116. In this embodiment, the contact of the 35 molten membrane with the cooling and solidiying liquid is effecte by use of the guide roller. Optionally, the molten membrane may be dischargea directly into the cooing and solidifying liquid instead. The molten membrane is completely cooled and solidified while it is travelling through the interior o~ the cooing tank 115 5 and then taken up on a ta~eup roller 118. In this while, the cooling and solidifying liquid 117 which is supplied via a line 119 is discharged via a line 120, then cooled to a prescribed temperature by a cooling device (such as, for example, a heat exchanger) 121, and 10 recycled. The membrane taken up as described above was then led into an extraction tank (not shown) filled with an extractant, there to be deprived of the organic filler by extraction. The membrane emanating from the extraction tank, when necessary, is subjected to 15 re-extraction, drying, and heat treatment, for example, before it is rewound. For the purpose of stabilizing the construction and the permeation property of the porous membrane to be produced the membrane is desired to be subjected to the heat treatment as fixed in a 20 prescribed length. The extraction of the organic filler from the membrane may be effected by the use of an extractin tank disposed before the step of the rewinding.
The polypropylne to be used as one of the raw 25 materials in the method of this invention need not be limited to homopol~ymer of propylene. It may be a block copolymer using propylene as the main component and additionally incorporating therein another monomer (such as, for example, polyethylene). Desirably, the 30 polypropylene is required to possess a melt index (M.I~) in the range of 5 to 70, preferably 10 to 40. Fuxther for the purpose of enhancing the strength of the membrane, the polypropylene to be used in the composition is desired to have a large molecular weight, 35 namely, a low M.I. Fox example, a mixture consisting of a species of polypropylene having a M.I. in the range of ;
: : .
. ~:
0.05 to 5 is used to advanrage. In all the species of polypropylene enumerated above, the homopolymer of propylene proves to be particulaxly advantageous, especially so where the homopolymer possesses high 5 crystallinity.
The organic filler is required to be uniformly dispersible in the polypropylene which is in a molten state and to be easily soluble in an extractant to be used later. Examples of the filler which fulfils this 10 requirement include liquid paraffin (number average molecular weight 100 to 2,000), ~ -olefin oligomers [such as, for example, ethylene oligomer (number average molecular weight 100 to ~,000), propylene oligomer (number average weight 100 to 2,000), and ethylene 15 oligomer (number average molecular weight 100 to 2,000)], paraffin wax (number average molecular weight 200 to 2,500), and various hydrocarbons. On the organic fillers enumerated above, the liquid paraffin proves to be particularly desirable.
The mixing ratio of the polyrpopylene and the aforementioned organic filler is such that the proportin of the organic filler to 100 part~ by weight of the propylene is in the range of 200 to 600 parts by weight, peferably 300 to 500 parts by weight. I fhte proportion 25 of the organic filler is less than 200 parts by weight, the flat~ilm typè porous polypropylene membrane to be produced possesses unduly low porosity and water permeability and fails to acquire sufficient permeation property. If this proportion exceeds 600 parts by 30 weight, the produced membrane exhibits unduly low viscosity and deficiency in workability. For the formulation of raw materials mentioned aboe, the mixture consisting of raw materials in a prescribed percentage composition is prepared (designed) by the premix method 35 which comprises melting and blending the mixture, -: ~
L 6 ~
extruding the resultant blend, and pelletizing the extruded blend by the use of biaxial type extruding machine, for example.
The crystalline seed forming agent to be 5 included in the raw materials for this invention is an organic heat-resistant substance possessing melting point of not less than 150C, preferably in the range of 200 to 250C, and a gelling point of not less than the crystallization starting piont of polyolefin~ The 10 crstalline seed forming agent of this description is used as one of the raw materials for the purpose causing contraction of the particles of polypropylene thereby controlling the gap b~tween the solid phases, namely the diameter of micropores to be formed. As examples of the lS crystalline seed forming agent, there can be cited 1,3,2,4-dibenzilyaene sorbitol, 1,3,2,4-bis(p-methylbenzilydene~ sorbitol, 1,3,2,4-bis(p-ethylbenzilydene)sorbitol, bis(4-t-butylphenyl)sodium phosphate, sodium benzoate, 20 adipic acid, talc and kaoline. Among other crystalline seed forming agents enuemxated above, 1,3,2,4-dibenzylidene sorbitol, 1,3,2,4-bis(p-ethylbenzilydene) sorbitol, and 1,3,2,4-bis(p-methylbenzylidene) sorbitol prove to be 25 advantageous because they do not appreciably dissolve out into the blood.
The mixing ratio of the propylene and the aforementioned crystalline seed forming agent is such that the proportion of the crstalline seed forming agent 30 to 100 parts by weight of the polypropylene i5 in the range of 0.1 to 5 parts by weight, preferably 0.2 to 1.0 part by weight.
As the cooling and solidifying liquid for this invention a solution exhibiting no compatibility with 35 the organic filler being used and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g, , ~
.
'J~ ~3 preferably 0.3 to 0.6 cal/g. As concrete e~amples of the cooling and solidifying liquid, there can be cited polyethers such as polyethylene glycol and water-soluble paraffins which are insoluble in the oragnic filler.
5 Among other cooling and solidifying liquids enumerated above, various species of polyethylene glycol prove to be particularly advanrageous, especially so when their average molecular weights fall in the range of 100 to 400. The species of polyethylene glycol possessing an 10 average molecular weight in the range o~ 18~ to 330 proves to be the most desirable selection. Such a liquid as exhibiting no compatibility with the organic filler being used and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g is used as the - 15 cooling and solidifying liquid for the following reason.
When a compound identical or similar to the aforementioned organic filler is used as the cooling and solidifying liquid, namely when a species of liquid paraffin is used as the organic filler and another 20 species of liquid paraffin possessing number average molecular weight approximating that of the first species of li~uid paraffin is used as the cooling and solidifying liquid, the produced membrane is enabled to contain pores in a prescribed density without entailing 25 any appreciable migration of the organic filler in the molten membrane. Further, since the specific heat is not unduly large, the polypropylene is crystallized smoothly at a proper cooling speed to form particles stably. During the course of this cooling, the 30 polypropylene dissolves out into the cooling and solidifying liquid before the polypropylene in the surface parts is solidified. As the result, a very large reticular structure is formed in the surface parts. When an inactive liquid exhibiting no 35 compatibility with the organic filler and possessing a large specific heat capacity of about 1.0 cal/g, is used ,~
as the cooling and solidifying liquid, the polypropylene is quickly cooled, the phase separation between the polypropylene is qulckly cooled the phase separation between the polypropylene does not suffciently proceed, 5 and the pores in the surface parts and those in the interior of the membrane are both small and the porosity of the membrane is 1ow becaue the cooling effect of the liquid is high.
In contast, when a liquid exhibiting no 10 compatibility with the aforementioned organic filler and possesisng a specific heat capacity in the range of 0.2 to 0.7 cal/g is used as the cooling and solidifyng liquid, the propylene is not suffered to dissolve out in the surface parts, the cooling speed of the t 15 polypropylene is proper, and the polypropylene is smoothly crstallized even in the surface parts with the composition ratio thereof retained intact. As the result, there can be formed a reticular structure which is not enlarged unduly even in the surface parts and 20 which is enabled to contain amply large pores fit for blood plasma separation even within the interior thereof.
The temperature of the cooling and solidifying liquid is desired to be in the range of 10 to 80C, 25 preferably 30 to 60C, for the following reason~ If this temperature is less than 10C, since ~the cooling and solidifying speed is so fast that the micropores to be formed consequently have a very small diameter.
Conversely, if the temperature exceeds 80C, the cooling 30 and solidifying treatment does not proceed amply and the molten emmbrane is liable to break in the cooling and solidifying liquid.
The membrane which has been throughly cooled and solidified in the cooling and solidifying tank is 35 brought into contact with the extractant to permit removal of the organic filler therefrom by extraction.
.. ~ .
..
~3~ ~~
This solution and extraction of the organic filler may be effected by the extraction tank method or the shower method which comprises advanting the membrane on a belt conveyor and causing the extractant to fall in the form 5 of shower OlltO the membrane in motion.
As the extractant, any liquid can be used on the sole condition that it should be incapable of dissolving the polypropylene forming the backbone of the porous membrane and acapable of dissolving and 10 extracting the organic filler. Examples of the liquid answering the description include such halogenated hydrocarbons as tetrachloromethane, 1,1,2-trichloro-1,2,2-trifluoroethane, trichlorofluoromethane, dichlorofuluoromethane, 15 1,1,2,2-tetrachloro-1,2-difluoroethane, trichloroethylene, and perchloroethylene. In the liquids enumerated above, chlorofluorinated hydrocarbons prove to be desirable in terms of ability to extract the organic filler and safety in the human system. Where a 20 sorbitol is used as the crystalline seed forming agent, a ketone may be incorporated in the extractant so as to remove the sorbitol from the porous membrane during the course of extraction and thereby to preclude the otherwise possible exudation of the sorbitol from the 25 surface of the porous membrane after the molding.
The falt-film type porous polypropylene membrane which is obtained as described above, when ; necessary, may be further subjected to a heat treatment.
; This heat treatment is carried out at a temperature 10 30 to 15C lower than the melting point of the polypropylene, specifically a temperature in the range of 110 to 150C, preferably 130 to 140C, for a period in the ragnge of 30 to 180 secondst prefarably 60 to ~0 seconds. Preparatory to the heat treatment, the porous 35 membrane must be fixed in a prescribed length. ~he flat-film type porou polypropylene membrane which is ~ 3 ~
produced as described above is useful as a membrane for the separation of blood into blood cells and blood plasma and as a microfiler for the removal of bacteria from blood. It is used particularly advantageously as a 5 membrane for the separation of blood plasma where the separted blood plasma is put to use as in the treatment of donorpheresis.
Example As an aid for further facilitating the 10 comprehension of this invention, a few working exampls will be cited below. There exampls are offered purely for the purpose of illustrating this invention and are not meant to restrict the scope of this in~netion in any respect.
15 Examples 1 through 3 and Controls 1 through 3:
By the use of a twin-screw extruder (produce dby Ikegai Iron Works, Ltd. and marketed under trademark designation of PCM-30-25), 100 parts by weight of a mixture of two polypropylne species possessing melt flow 20 indexes of 30 and 0.3 (mixing ratio 100 : 40 by weight), varying proportions of liquid paraffin (nul~er average molecular weight 324), and 1,3,2,~-bis(p-ethylbenzylidene)sorbitol as a crystalline seed forming agent indicated in Table 10 were melted and 25 kneaded and pelletized. By the aforementioned extruder, the pellets were melted at a varying temperature in the range of 150 to 200C, extruded through a T die 0.6 mm in slit width into the air, allowed to fall onto a guide roller in a colling liquid tank disposed directly below 30 the T die, led into the cooling and solidifying liquid by the rotation of the roller to be cooled and solidified therein, and thereafter taken up. The kind and temperature of the cooling and solidifying liquid used in this case were as shown in Table 1. From the 35 film thus taken up, a square (about 200 x 200 mm) was cut off, fixed in both the longitudinal and lateral ,:
.. . . .
,,: , ' .
directions, immersed four times in 1,1,2-trichlor-1,2,2-trifluoroethane (liquid temeprature 25C) for 10 rninutes each to effect expulsion of the liquid para~fin, and then heat trea-ted 5 in the air at 135C ~or 2 minutes.
The flat-film type porous polypropylne membrane consequently obtained was tested for wall thickness, bubble point, porosity, water permeation, and highest blood plasma separation speed~ The results are 10 shown in Table 1.
Then, to determined the microstructure of the flat-film type porous polypropylene membrane, various portions of the membrane were observed under a scanning electron microscope (produced by JEOL and marketed under 15 product code of "JSM-840"~. Fig. 3 is a photomicrograph of the surface (x 1,000) of the flat-film type porous polyrpopylene membrane of Example 1, Fiy. 4 of the partial cross section (x 2,500) of the flat-film type prous polypropylene membrane of Example 1, Fig. 5 of the 20 surface (x 1,000) the flat-film type porous polypropylene membrane of Control 1, and Fig. 6 of the partial cross section (x 3,000) of the flat-film type porous polypropylene membrane of Control 1, respectively taken under the electron microscope. It is clearly 25 noted from Fig. 3, and Fig. 4 that the flat-film type porous polypropylene membrane of Exmaple I according with the present invention possessed practically equal reticular structure in the surface parts and in the interior of the membrane, the surface layers had a 30 virtually negligible thickness (about 0.5~ of the total membrane thickness), and the reticular structure had attained full development even in the interior of the membrane. In contrast t the flat-film type porous polypropylene membrane obtained by used liquid paraffin 35 as the cooling and solidifying liquid (control 1), as clearly noted from Fig. 5 and Fig. 6, possessed as fully trade-marlc ~. 3 ~
developed A reticular structure in the interior of the membrane as in the membrane of E~maple 1, possessed fairly rough reticular s-tructure in the surface paxts, and had surface layers of a fairly large -thickness 5 (about 24.0% of the total thickness of the membrane).
The comparison offers a definite evidence that the falt-film type porous polypropylene membrne of Example l according with the present invention ~uffered sparingly from occulsion of blood cells~
Separately, life-size laminate modules severally incorporateing therein the falt-film type porous polypropylene memebrane of E~ample l and Control l were operated t~ effect blood plasma separation of bovine blood, to compare the flat-fim type porous 15 polypropylene membrane in ability o~ blood plasma separation. Results are shown in Fig. 7 - 9. Fig. 7 shows the relation between the speed of blood plasma separation (Qf) and the total intermembranous pressure (T.M.P.) and Fig. 8 the relation between the T.M.P~ and 20 the amount of free hemoglobin ( ~ Hb).
Control 4:
For the purpoe of comparison, a commercially availabel cellulose acetate membrane (C~; produced by Toyo Filter Paper Co., ltd.) was similarly tested for 25 thickness of membrane, bubble point, porosity, water permeation, and highest blood plasma separation speed.
The results are shown in Table l.
* trade-mark , o 1 3 ~
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O^ ~D ~O ~O (` i` U~ ~
~ dP
~ ~ ~ ~1 0 0 0 m ~ ~ ~ o ~ o O o E t~ E~ ,~ ~ _~ ,1 ,~ ~1 , _l~ r.
o ~ 0 ~, ul ~ R o o o o o o E u ,1 ~
~1 0 ,1 0 Q.
r .
~ O C~
U-- ul o In a:\ o o ~ ~J ~ ~) N
aJ S --1 CJ ~.,1 E~ O
~ O O ~ ra q~ho ho ''I h tJ' ~ q.l RE~
~1 C) ~ O q I h :~
~' S R, h h P. U
a) O : : .1N `1 C: ~1 ~1 O O ,,1 ~r-l N ,.
u ~ ~ ~~ ~ a~
~n o ~ S O O ~D O O O ~
h h ~1 o o ~ o o Ul o 3 ~ 1 U
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O O O O
h h h h X X X O O O O
E 1 1~ W [.) U U
.
.
, 131~
It is clearly noted from Table 1 that the flat-film type porous polypropylene membranes of the present invention (Examples 1 through 3) exhibited high porosity and water permeability and also possessed high 5 blood plasma separation speeed.
Further the flat-film type porous polypropylene membranes of this invention, owing to their membranous structure, suffered sparingly from occlusion of blood cells and they had an advatnage of 10 hardly admitting of hemolysis as shown in Figs. 7 and 8.
In contrast, the flat-film type porous polypropylene membranes of Conotrols 1 through 3 which used liquid paraffin or halo~enated hydrocarbon as the cooling liquid were liable to induce hemolysis and ocnsequently : 15 were not allowed to use any large intermembranous pressure, thouyh they exhibited as high blood plasma eparation speed as the flat-film type porous polypropylene membranes of the present in~ention. In terms of the permeability to the componenets of blood 20 plasma, the flat-film type porous polypropylene membrane of this invention (Example 3~ was favorably comparable with that of Control 1 which had a large surface pore - diameter.
The various terms used in the present 25 specification concerning the Flat-film tyep porous polypropylene membrane and the methods used for the determination of the properties mentioned herein are - de~iend below.
Bubble point This property was determined in accordance with the method of correction specified in ASTM F316, using a stainless steel holder 47 mm in diameter and -~ isopropyl alcohol as a liquid alcohol. The pressure applied was continuously increased until a continuous 35 line of nitrogen bubbles began to rise uniformly and ' . .
. ~
.
.~
~ ~ 3~
incessantly from the center of the filter through the isopropyl alcohol. The pressure at this point was reported as bubble point.
Thickness of membrane This property was determined by actually measuring the thickness of a given membrane with the aid of micrometer.
Porosity ~ ~ . . . = _ A given flat-film type porous polypropylene 10 membrane was immersed in ethanol and then hydrated by means of displacement of ethanol with wa-ter and the weight of the water (Wp) conse~uently contained therein was determined. The porosity was calculated in accordance with the fol.lowlng formula:
(Wp-Ww) x 100 (Ww/P) + (Wp-Ww) wherein Ww stands for the weight of the membrane in the dry state and P g/ml for the density of the polymer.
Water permeation .
Water at 25C was caused to permeate a give membrane measuring 1.45 x 10 3 m2 in area under application of a pressure of 0.7 kgf/cm2. The -time required for 100 ml of water to pass through the membrane was clocked and reported as water pemation.
25 Highest blood pLasma separation speed (Qf max) This property was determined by use of a circuit illustrated in Fig. 2. In a module 30 possessing a membrane surface area of 0.4 m2~ fresh bovine blood incorporating therein heparin of a 30 hematocrit value of 40~ (5,000 U/liter) was circulated in a flow volume of lOOml/min at a pressure loss of 30 mmHg, with the flow volume of filtration pump successively increased from 10 ml/min to 10, 15, 20, 25, 30, 40, and 42 at intervals of 30 minutes. The amount .
;' 6 ~
of filtrate immediately before the increase o~ T~M.P.
within an interval of 30 minutes surpassed 20 mmHg was found and reported as Qf max.
in + POut/2 - Pfil is presumed.
5 In ~ig. 2, Gl, G2, and G3 each denote a pressure meter, the pressure of Gl is expressed as Pin, that of Ga as Pfil, and that of G3 as PoUt respectively, Every P
indicated in the diagram stands for a pump.
Average pore diameter This property was determined by actually measuring the size of pores, in a given membrane with a mercury porosity.
~Industrial Utility of the Invention~
As described above, this invention concerns a 15 flat-film type porous polypropylene membrane possessing a microreticular structure, characterized by the fact that either or both of the opposite surface region of the porous membrane forms a surface layer possessing an average pore diameter in the range of 0.1 to 5.0~m, a 20 bubble point of not more than 2.0 kgf/cm2, a porosity in the range of 60 to 85%, and a water permeability of not less than 100 ml/min.mmHg.m2, and the mem~rane possesses a wall thickness in the range of 30 to 300~m. Thus, the flat-film type porous polypropylene membrane exhibits 25 high porosity and water permeability. When it is used for blood plasma separation, it suffers sparinyly from clogging of pores with proteins or blood cells, effects separation of blood plasma at a high speed, and entails only slight occlusion of blood cells and hardly includes 30 hemolysis. Owing to these features, the falt-film type porous polypropylene membrane is used advantageously for blood plasma separation, i.e. the separtion of blood into blooa cells and blood plasma~. It is particularly useful as a membrane for bloood plasma separation where 35 the separated blood plasma is put to use as in the donorpheresis. The flat-film type porous polypropylene -~4-`:"
' ' ' ' ' ~
' . . ' ' ~ 3 ~
membrane of this invention is enabled to manifest these highly desirable properties still more to advantage when the bubble point is not more than 1.8 kgf/cm2, the water permeation not less than 140ml/min.mmHg.m2, and the 5 ratio of shrinkage due to 120 minutes' heat treatment at 121C is not more than 6.0%.
This invention also concerns a method for the production of a flat-film type porous polypropylene membrane, characterized by mixing 100 parts by weight of 10 polypropylene, 200 to 600 parts by weight of an organic ~iller uniformly dispersible in the polypropylene in the molten state, and 0.1 to 5.0 parts by weight of a crystalline seed ~orming agent, discharging the resultant mixture in a molten state through a die 15 thereby producing a molten membrane in the form of a flat film, cooling and solidifying liquid exhibiting no compatibility to the organic filler and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g, and then bringing the cooled and solidified membrane 20 into contact with an extractant incapable of dissolving the polypropylene and capable of dissolving the organic filler thereby removing the organic filler form the membrane by extraction. This method is capalbe of easily producing the flat-film type porous polypropylene 25 membrane possessing the aforementioned outstanding properties. The properties of the flat-film type porous polypropylene membrane are stabilized to a greated extent when the method described above further comprises ; causing the flat-film type porous polypropylene membrane 30 which results from the removal of the organic filler by extraction to be fixed in a prescribed length and subjected to a heat treatment at a temperature in the range of 110 to 140C. The flat-film type poxous polypropylene membrane o~ high grade can be obtained 35 easily when the contact of the molten membrane with the cooling and solidifying liquid is effected by having a .
11 3 ~ 3 1~
guide roller disposed in the cooling and solidfying liquid, discharging the molten mix~ure onto the guide roller, and causing the molten mixture to be led into the cooilng and solidifying liquid by the rotation of 5 the guide roller. The properties of te flat-film type porous polypropylene membrane are further enhanced when the cooling and solidifying liquid is a polyether, the polypropylene consists of a species of polypropylene possessing a melt index in the range of 5 to 40 and 0 to 10 50% by weight of another species of polypropylene possessing a melt index in the range of 0.05 to 5, the crystalline seed forming agent is incorporated in the mixtrue in a proportion falling in the range of 0.2 to 1.0 part by eight, the crystalline seed forminng agent -~. 15 is an organic heat-resistant substance possessing melting point of not less than 150C and a gelling point not less than the crystallization starting point of polypropylene, and the extractant is either a halogenated hydrocarbon or a mixtue of a halogenated 20 hydrocarbon with a ketone.
Claims (12)
1. A flat-film type porous polypropylene membrane possessing a microreticular structure, characterized by the fact that either or both of the opposite surface region of said porous membrane forms a surface layer possessing an average pore diameter in the range of 0.1 to 5.0 µm, a bubble point of not more than 2.0 kgf/cm2, a porosity in the range of 60 to 85%, and a water permeability of not less than 100 m1/min.mmHg.m2 and said membrane possesses wall thickness in the range of 30 to 300µm.
2. A flat-film porous polypropylene membrane according to Claim 1, wherein said bubble point is not more than 1.8 kgf/cm2.
3. A flat-film type porous polypropylene membrane according to Claim 1 or Claim 2, wherein said water permeation is not less than 140 m1/min.mmHg.m2.
4. A flat-film type porous polypropylene membrane according to Claim 1 or 2, wherein the shrinkage by 120 minutes' heat treatment at 121°C is not more than 6.0%.
5. A method for the production of a flat-film type porous polypropylene membrane, characterized by mixing 100 parts by weight of polypropylene, 200 to 600 parts by weight of an organic filler uniformly dispersible in the polypropylene in the molten state, and 0.1 to 5.0 parts by weight of a crystalline seed forming agent, discharging the resultant mixture in a molten state through a die thereby producing a molten membrane in the form of a flat film, cooling and solidifying the molten membrane by contact with a colling and solidifying liquid exhibiting no compatibility to the organic filler and possessing a specific heat capacity in the range of 0.2 to 0.7 cal/g, and then bringing incapable of dissolving the polypropylene and capable of dissolving the organic filler thereby removing the organic filler from the membranes by extraction.
6. A method according to Claim 5, which further comprises causing the porous polypropylene membrane obtained after said removal of said organic filler by extraction to be fixed in a prescribed length and subjected to a heat treatment at a temperature in the range of 110° to 140°C.
7. A method according to Claim 5 or Claim 6, wherein said contact of the molten membrane with said cooling and solidifying liquid is effected by having a guide roller disposed in said cooing and solidifying liquid, allowing part of said guide roller to rise above the surface of said cooling and solidifying liquid, causing said mixture to be discharged onto said guide roller, and allowing said mixture to be led into said cooling and solidifying liquid by the rotation of said guide roller.
8. A method according to Claim 5, wherein said cooling and solidifying liquid is a polyether.
9. A method according to Claim 5, wherein said polypropylene consists of a species of polypropylene possessing a melt index in the range of 5 to 40 and 0 to 50% by weight of another species of polypropylene possessing a melt index in the range of 0.05 to 5.
10. a method according to Claim 5, wherein said crystalline seed forming agent is incorporated in a proportion falling in the range of 0.1 to 1.0 part by weight.
11. A method according to Claim 5, wherein said crystalline seed forming agent is an organic heatresistant substance possessing a melting point of not less than 150°C and a gelling point of not less than the crystallization starting point of the polypropylene.
12. A method according to Claim 5, wherein said extractant is halogenated hydrocarbon or a mixture of said halogenated hydrocarbon with a ketone.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56728/1987 | 1987-03-13 | ||
| JP5672887A JPS63224702A (en) | 1987-03-13 | 1987-03-13 | Polypropylene porous membrane and its production |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1310160C true CA1310160C (en) | 1992-11-17 |
Family
ID=13035561
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000560896A Expired - Lifetime CA1310160C (en) | 1987-03-13 | 1988-03-09 | Porous polypropylene hollow fiber membrane, method for production thereof and artificial lung |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS63224702A (en) |
| CA (1) | CA1310160C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007061673A (en) * | 2005-08-29 | 2007-03-15 | Toray Ind Inc | Microporous polypropylene sheet for medical separation membrane, and medical separation membrane using the same |
-
1987
- 1987-03-13 JP JP5672887A patent/JPS63224702A/en active Granted
-
1988
- 1988-03-09 CA CA000560896A patent/CA1310160C/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0555174B2 (en) | 1993-08-16 |
| JPS63224702A (en) | 1988-09-19 |
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