Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D67/00—Processes specially adapted for manufacturing semi-permeable membranes for separation processes or apparatus
  • B01D67/0081—After-treatment of organic or inorganic membranes
  • B01D67/0088—Physical treatment with compounds, e.g. swelling, coating or impregnation
• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
  • B01D—SEPARATION
  • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
  • B01D63/02—Hollow fibre modules
  • B01D63/021—Manufacturing thereof

Definitions

• Hydrophobic membranes and particularly microporous membranes, have proven useful in the field of blood handling for oxygenation of blood, and also for the practice of membrane plasmapheresis in which plasma from the blood passes through the membrane for collection, while the cells are retained.
• corona treatment is used to provide a hydrophobic microporous membrane with a hydrophilic outer surface in which the micropores retain their hydrophobic characteristic.
• U.S. Patent No. 4,087,567 teaches an anticoagulent coating composition suitable for coating the interior sur ⁇ faces of a blood microsample collection tube such as a capillary tube, typically made of glass.
• the coating composition consists essentially of ethylene diamine tetraacetate held in a matrix of polyvinyl pyrrolidone.
• none of these systems are suitable for the purpose of this invention of rendering hydrophilic with an organic solvent bundles of hollow fibers or other membrane made out of a hydrophobic plastic such as polypropylene, particularly in a manner which is highly compatible with blood, exhibiting very low hemolysis and essentially no toxicity in the doses applied.
• hydrophobic membrane typically con ⁇ taining micropores of less than 10 microns
• hydrophilic membrane can be rendered hydrophilic to facilitate the flow of aqueous liquids such as blood therethrough, with a separated material passing through the micropores.
• This invention is particularly contemplated for use in separation devices containing bundles of hydrophobic, microporous hollow fibers, but the invention is not intended to be limited to such use, but can be used as desired in the medical or other fields for generally improving the flow characteris ⁇ tics of aqueous liquids through narrow flow channels defined by hydrophobic plastic surfaces.
• the surface active agent consists essentially of a nonionic ester of a carbohydrate moiety and an organic monoacid of 8 to 30 carbon atoms.
• the volatile organic solvent is a Freon-type material, i.e., a fluorochlorocarbon compound of no more than about 3 carbon atoms.
• a fluorochlorocarbon compound of no more than about 3 carbon atoms.
• the specific sur ⁇ face active agents of this invention exhibit improved solubility in such organic solvent materials. It is also understood that a minor amount of hydrogen may also be present in the fluorochlorocarbon compounds utilized in this invention if desired.
• the surface active agents used in this invention also exhibit improvements over surface active agents of the polyoxyalkylene glycol type in that the surface active agents of this invention are more efficient, more easily metabolized, and are subject to lower degree of toxic - reaction.
• a specific example of the surface active agent of this invention which is preferred is a mixture of monoesters of sorbitan with capric, lauric, myristic, palmitic and/or oleic acids.
• the mixture may include the following typical weight percentages of mono- esters, sold.as Span 20 by ICI Americas Inc.: sorbitan caprate 1.1%; sorbitan laurate 43.5%; sorbitan myristate 27.8%; sorbitan palmitate 19.2%; and sorbitan oleate 8.4%.
• other analogous esters can be used, pure or mixed, preferably monoesters of carbohydrates such as sorbitan, glucose, fructose, or other metabolizable carbo ⁇ hydrates of preferably 5 to 6 carbon atoms.
• the organic monoacids used of 8 to 30, and preferably 10 to 20, carbon atoms, may be any appropriate monoacid which reacts with the carbohydrate moiety to preferably form a monoester.
• OM i.e., one carbohydrate molecule reacted with one monoacid molecule.
• the acids which may be used include those des ⁇ cribed above or others such as tridecanoic acid, or mixed acids such as linseed oil acids, to provide an appropriate hydrophobic portion, combined with the hydrophilic carbohydrate moiety to form the desired surface active agent.
• the volatile organic solvent utilized preferably is selected from the group consisting of alcohols of no more than 3 carbon atoms, for example, methanol, ethanol, or isopropanol, ethers of no more than 4 carbon atoms, for example diethylether, and fluorochlorocarbon compounds of no more than about 3 carbon atoms, i.e., Freon-type materials such as l,l,2-trichloro-l,2,2-trifluoroethane.
• the fluorochlorocarbon compounds of no more than 3 carbon atoms are preferred because of their high volatility and low flam ability.
• the vapors of the fluorochlorocarbon compounds or other solvents may be recycled for condensa ⁇ tion and reuse.
• the hollow fibers treated in accordance with this invention may preferably define micropores in their walls of a size of typically no more than a 5 micron and preferably 1 micron mean diameter, and preferably sized to permit blood plasma to flow therethrough, but to prevent the passage of substantial numbers of blood cells therethrough.
• the mean pore size it is generally preferable for the mean pore size to be no greater than 0.6 micron, and typically no greater than 0.55 micron, down to 0.1 micron.
• the pores are at least 0.05 micron in diameter.
• the size of the pores may be about 0.3 to 0.55 micron. At lower pore sizes, particularly below 0.1 micron, plasma may be frac- tionated, separating out lower molecular weight components from higher molecular weight components of the plasma.
• the hollow fiber may be made of polypropylene as stated above, it may also be made of any hydrophobic material as may be desired, for example polyethylene, or copolymers containing polypropylene or polyethylene units copolymerized with butadiene, divinylbenzene, styrene, or other units, as well as other hydrophobic plastic materials.
• the bore diameters of the hollow fibers are preferably from 0.2 to 0.5 millimeter.
• Figure 1 is a longitudinal sectional view of a diffusion device in accordance with this inven ⁇ tion.
• Figure 2 is a greatly enlarged longitudinal sectional view of a single, hollow fiber in accordance with this invention.
• Figure 1 shows a diffusion device which can be used as a membrane plasmapheresis device.
• the overall structure of the device may be in accordance with conventional design for a hollow fiber separation device (e.g., a dialyzer), except as otherwise described herein.
• a hollow fiber separation device e.g., a dialyzer
• Hollow tubular casing 10 is shown to contain a bundle 12 of hollow, hydrophobic fibers made preferably of poly ⁇ propylene or a hydrophobic copolymer thereof.
• casing 10 defines manifold end caps 14 surrounding an end mass of potting material 16, through which the individual fibers 18 of bundle 12 penetrate to provide flow communication between inlet 20 and outlet 22 through the bores 24 of hollow fibers 18. This serves typically as the blood flow path through the separation device.
• Outlet port 26 communicates with the spaces within bundle 12 but outside of the individual fibers 18, and also manifold spaces 28, 32.
• inlet port 30 can be provided to provide oxygen to manifold space 32, where the oxygen flows between the individual, hollow fibers 18 to collect in manifold space 28 and to pass outwardly through port 26.
• inlet port 30 is unnecessary, but may e present as a second outlet.
• the product passing through outlet port 26 is blood plasma, which passes through the wall of hollow fiber 18 from bore 24 to the space between the individual fibers 18, for draining out of outlet port 26, and also port 30, if desired.
• the hollow fibers 18 contain a multitude of micropores 34 which are typically less than 1 micron in size, and are preferably about 0.3 to 0.55 micron in the case of membrane plasmapheresis.
• an impure form of sorbitan fatty acid esters for example, Span 20 sold by ICI Americas
• Span 20 sold by ICI Americas
• an impure form of sorbitan fatty acid esters can be mixed in a proportion of, for example about 10 to 16.3 weight percent in a reactor with the balance being l,l,2-trichloro-l,2,2-trifluoroethane (Freon 113) and stirred or shaken to dissolve the Span 20 into the Freon material. The mixture is then allowed to stand quietly until it fractionates into two separate fractions.
• the lower fraction is a solution of Freon 113 and the purified sorbitan monoester mixture (hereafter called sorbitan monolaurate), and is collected for further use.
• the collected solution is further diluted with Freon 113 to a sorbitan monolaurate concentration of about 1.9 to 3.2 percent by weight.
• a bundle 12 of hollow fibers, installed in casing 10 and sealed with sealant 16 in con- ventional manner, with the end caps 14 off, is positioned to receive the diluted Freon solution of sorbitan mono ⁇ laurate through port 26, with the solution passing into bores 24 of the hollow fibers through micropores 34.
• the hollow fibers are then allowed to drain by gravity, cen- trifuged for final draining, and dried in an oven at about 135° F.
• a film of sorbitan monolaurate adheres to the surfaces of each fiber 18 including the inner surfaces of micropores 34.
• end caps 14 may be applied to the device, and it may be sterilized by treatment with ethylene oxide or other desired sterili ⁇ zation technique.
• the resulting device readily receives blood flow in a uniform, complete manner through micropores of the individual fibers 18 for membrane plasmapheresis, or blood fractionation, or for other separation techniques with other aqueous solutions than blood.
• Such treatment with blood has been shown to be feasible without unacceptable levels of hemolysis or other ill effect.

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• Chemical & Material Sciences (AREA)
• Engineering & Computer Science (AREA)
• Manufacturing & Machinery (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Inorganic Chemistry (AREA)
• Separation Using Semi-Permeable Membranes (AREA)
• External Artificial Organs (AREA)

Priority Applications (2)

Applications Claiming Priority (1)

Publications (1)

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Family Applications (1)

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Cited By (14)

Citations (4)

• 1983
  • 1983-04-06 WO PCT/US1983/000495 patent/WO1984000015A1/en not_active Application Discontinuation
  • 1983-04-06 EP EP83901547A patent/EP0111499A1/en not_active Withdrawn
  • 1983-04-21 ZA ZA832803A patent/ZA832803B/xx unknown
  • 1983-06-06 IT IT21483/83A patent/IT1163465B/it active

Patent Citations (4)

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