EP0111499A1

EP0111499A1 - Wettable hydrophobic hollow fibers

Info

Publication number: EP0111499A1
Application number: EP83901547A
Authority: EP
Inventors: Daniel R. Boggs; Mark W. Mcglothlin
Original assignee: Baxter Travenol Laboratories Inc
Current assignee: Baxter International Inc
Priority date: 1982-06-14
Filing date: 1983-04-06
Publication date: 1984-06-27
Also published as: IT8321483A0; IT1163465B; ZA832803B; IT8321483A1; WO1984000015A1

Abstract

Un faisceau (12) de membranes hydrophobes (18) composées de plastique hydrophobe contenant des micropores ayant un diamètre inférieur à 10 microns est traité avec un solvant organique contenant un agent tensioactif du type monoester pour recouvrir les micropores et permettre à un liquide aqueux de s'écouler facilement au travers des micropores. Les membranes recouvertes (18) ne sont pas toxiques et sont particulièrement compatibles avec le sang, présentant un taux d'hémolyse très bas.A bundle (12) of hydrophobic membranes (18) composed of hydrophobic plastic containing micropores having a diameter of less than 10 microns is treated with an organic solvent containing a monoester-type surfactant to coat the micropores and allow an aqueous liquid to settle. 'flow easily through the micropores. The coated membranes (18) are not toxic and are particularly compatible with blood, showing a very low rate of hemolysis.

Description

WETTAB E HYDROPHOBIC HOLLOW FIBERS

Technical Field and Prior Art

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.

It would be desirable to make use of the known ad an- tageous flow and diffusion characteristics of a hollow fiber design of membrane in which a bundle of hollow microporous hydrophobic fibers carry blood or other fluid, while performing a separation process with respect to the blood, for example, by allowing plasma to pass through the micropores of the fibers. The blood cells, and in some - instances high molecular weight components of the plasma, cannot pass through the micropores.

However, in the event that microporous hydrophobic material is used, it is difficult to get blood or any other aqueous solutions to flow through the micropores because of their hydrophobic nature.

In Leonard U.S. patent application Serial No. 901,945, filed May 1, 1978, corona treatment is used to provide a hydrophobic microporous membrane with a hydrophilic outer surface in which the micropores retain their hydrophobic characteristic.

It is taught in Japanese Patent No. 79/153872 to render porous, polypropylene membranes hydrophilic by treatment with a water solution of sodium lauryl sulfate or the like (Chemical Abstracts 92j 148121k (1980)).

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. However, 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.

-Description of the Invention

By this invention hydrophobic membrane, typically con¬ taining micropores of less than 10 microns, 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.

In accordance with this invention, one may apply to the bores of a bundle of hollow fibers made of a hydro¬ phobic plastic such as polypropylene a solution of 0.3 to 14, and preferably 1.9 to 3.2, weight percent of a sur¬ face active agent in a volatile organic solvent. The surface active agent consists essentially of a nonionic ester of a carbohydrate moiety and an organic monoacid of 8 to 30 carbon atoms. Thereafter, the hollow fiber is dried to cause the surface active agent to coat the surfaces of the fibers, including their micropores, whereby aqueous liquids can easily flow therethrough.

O v. It has been found that this particular family of sur¬ face active agents is particularly compatible with blood, with lower hemolysis, for example, than other candidate surface active agents such as polyoxyalkylene glycol type surface active agents.

It is preferred for the volatile organic solvent to be a Freon-type material, i.e., 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. As a specific example, 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%. However, 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. To this end 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. Generally the pores are at least 0.05 micron in diameter.

Generally if the purpose of use of the treated hollow fibers is to separate plasma from blood cells, 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. While 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.

Description of the Drawings

• In the drawings, 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.

Description of Specific Embodiment

Referring to the drawings. 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.

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. As is con¬ ventional, 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. In the case of an oxygena- tor, 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.

In the event that the device is a membrane plasma- pheresis device, 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. Typically, 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.

After building of the separation device as shown in Figure 1, substantial difficulties may exist in passing aqueous solutions such as blood through the micropores 34 of hollow fibers 18, because of the natural hydrophobic nature of the material from which they are made. Accordingly, an impure form of sorbitan fatty acid esters (for example, Span 20 sold by ICI Americas) 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. Thus a film of sorbitan monolaurate adheres to the surfaces of each fiber 18 including the inner surfaces of micropores 34. Following this, 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.

The above has been offered for illustrative purposes only, and is not intended to limit the scope of the inven¬ tion of this application, which is as defined in the claims below.

Claims

THAT WHICH IS CLAIMED IS:

1. The method of applying a hydrophobic membrane made of hydrophobic plastic, containing micropores of less than 10 microns diameter, a solution of 0.3 to 14 weight per- cent of a -surface active agent in a volatile organic solvent, said surface active agent consisting essentially of a nonionic ester of a carbohydrate moiety and an organic monoacid of 8 to 30 carbon atoms, and thereafter drying said membrane to cause said surface active agent to coat said micropores, whereby aqueous liquids easily flow through said micropores.

2. The method of Claim 1 in which said membrane is a bundle of hollow fibers which define micropores in their walls of a size to permit blood plasma to flow there- through but to prevent the passage of substantial numbers of blood cells therethrough.

3. The method of Claim 2 in which said hollow fibers are made of polypropylene.

4. The method of Claim 2 in which said volatile or- ganic solvent is selected from the group consisting of alcohols of no more than 3 carbon atoms, ethers of no more than 4 carbon atoms, and fluorochlorocarbon compounds of no more than 3 carbon atoms.

5. The method of Claim 2 in which the bore diameter of said hollow fiber is from 0.2 to 0.5 mm. and said hollow fibers define micropores in its wall of no more than 1 micron diameter.

6. The method of Claim 2 in which said surface activ agent is a raonoester.

7. The method of Claim 6 in which said surface activ agent is sorbitan monolaurate.

8. The method of applying to the bores of a bundle o hollow fibers made of hydrophobic plastic having micro¬ pores less than 10 microns in diameter a solution of 0.3 to 14 weight percent of a surface active agent in a vola¬ tile organic solvent consisting essentially of a fluoro- chlorocarbon compound of no more than 3 carbon atoms, sai surface active agent comprising a nonionic monoester of a carbohydrate moiety and an organic monoacid of 10 to 20 carbon atoms, and thereafter drying said bundle of hollow fibers to cause said surface active agent to coat the bores of said fibers, whereby aqueous liquids easily flow therethrough.

9. The method of Claim 8 in which said hollow fibers are made of polypropylene.

10. The method of Claim 9 in which said hollow fiber define micropores in their wall of less than 0.05 to 0.6 micron mean diameter to permit blood plasma to flow there through but to prevent the passage of substantial numbers of blood cells therethrough.

11. The method of Claim 10 in which said organic εol vent is l,l,2-trichloro~l,2,2-trifluoroethane.

12. The method of Claim 11 in which said surface active agent is a mixture of sorbitan monoesters, dissolved in a solution concentration of 1.9 to 3.2 weigh percent.

13. A membrane made of hydrophobic plastic having micropores of no more than essentially 5 microns mean diameter, said micropores being coated with a film of a surface active agent consisting essentially of a nonionic ^" ester of a carbohydrate moiety and an organic monoacid of 8 to 30 carbon atoms.

14. The membrane of Claim 13 in which said surface active agent is a monoester.

15. The membrane of Claim 13 in which said surface active agent is a mixture of monesters including sorbitan monolaurate.

16. The membrane of Claim 13 which is made of poly¬ propylene.

17. The membrane of Claim 13 which is a hollow fiber defining micropores in its wall no more than 1 micron in diameter and of a size to permit blood plasma to flow therethrough but to prevent the passage of substantial numbers of blood cells therethrough.

18. The hollow fiber of Claim 17 having a bore diameter of 0.2 to 0.8 millimeter and defining micropores in its wall of 0.05 to 0.6 micron mean diameter.

19. A bundle of the hollow fibers of Claim 18.

20. A bundle of hollow fibers made of hydrophobic plastic and having micropores of a mean diameter of 0.1 to 0.6 micron, said micropores carrying a coating of a non¬ ionic monoester of a carbohydrate moiety and an organic monoacid of 10 to 20 carbon atoms.

21. The bundle of Claim 20 in which said monoester is sorbitan monolaurate.

22. The bundle of Claim 20 in which said hollow fibers define micropores in their walls of a size to permit blood plasma to flow therethrough but to prevent the passage of substantial numbers of blood cells there¬ through.

23. The bundle of Claim 22 in which said hollow fibers are made of polypropylene.

24. The bundle of Claim 23 in which the bore diameter of said hollow fibers is from 0.2 to 0.5 millimeter.

25. A .membrane plasmapheresis device made from the bundle of Claim 24.

OMM