1. Field of Invention
The invention relates to a process for producing a hydrophobic membrane using a thermally induced phase separation process in accordance with the preamble of Claim 1, the membrane having a sponge-like, open-pored, microporous structure, and to the use of the membrane for gas exchange processes, in particular oxygenation of blood, and for gas separation processes.
2. Description of Related Art
In a multitude of applications in the fields of chemistry, biochemistry, or medicine, the problem arises of separating gaseous components from liquids or adding such components to the liquids. For such gas exchange processes, there is increasing use of membranes that serve as a separation membrane between the respective liquid, from which a gaseous component is to be separated or to which a gaseous component is to be added, and a fluid that serves to absorb or release this gaseous component. The fluid in this case can be either a gas or a liquid containing the gas component to be exchanged or capable of absorbing it. Using such membranes, a large surface can be provided for gas exchange and, if required, direct contact between the liquid and fluid can be avoided.
Membranes are also used in many different ways to separate individual gas components from a mixture of different gases. In such membrane-based gas separation processes, the gas mixture to be separated is directed over the surface of a membrane usable for gas separation. Sorption and diffusion mechanisms result in a transport of the gas components through the membrane wall, with the transport of the individual gas components of the mixture occurring at different rates. This causes an enrichment of the permeate stream passing through the membrane by the most rapidly permeating gas component, while the retentate stream is enriched by the components that permeate less readily.
This ability to separate individual gas components from a gas mixture using membranes finds numerous applications. For example, membrane-based gas separation systems can be used to enrich the oxygen content of air to increase combustion efficiency or to enrich nitrogen in the air for applications requiring an inert atmosphere.
An important application of membrane-based gas exchange processes in the medical field is for oxygenators, also called artificial lungs. In these oxygenators, which are used in open-heart operations, for example, oxygenation of blood and removal of carbon dioxide from the blood take place. Generally, bundles of hollow-fiber membranes are used for such oxygenators. Venous blood flows in this case in the exterior space around the hollow-fiber membranes, while air, oxygen-enriched air, or even pure oxygen, i.e., a gas, is passed through the lumen of the hollow-fiber membranes. Via the membranes, there is contact between the blood and the gas, enabling transport of oxygen into the blood and simultaneously transport of carbon dioxide from the blood into the gas.
In order to provide the blood with sufficient oxygen and at the same time to remove carbon dioxide from the blood to a sufficient extent, the membranes must ensure a high degree of gas transport: a sufficient amount of oxygen must be transferred from the gas side of the membrane to the blood side and, conversely, a sufficient amount of carbon dioxide from the blood side of the membrane to the gas side, i.e., the gas flow or gas transfer rates, expressed as the gas volume transported per unit of time and membrane surface area from one membrane side to the other, must be high. A decisive influence on the transfer rates is exerted by the porosity of the membrane, since only in the case of sufficiently high porosity can adequate transfer rates be attained.
A number of oxygenators are in use that contain hollow-fiber membranes with open-pored, microporous structure. One way to produce this type of membrane for gas exchange, such as for oxygenation, is described in DE-A-28 33 493. Using the process in accordance with this specification, membranes with up to 90% by volume of interconnected pores can be produced from meltable thermoplastic polymers. The process is based on a thermally induced phase separation process with liquid-liquid phase separation. In this process, a homogeneous single-phase solution is first prepared from the thermoplastic polymer and a compatible component that forms a binary system with the polymer, the system in the liquid state of aggregation having a range of full miscibility and a range with a miscibility gap, and this solution is then extruded into a bath that is substantially chemically inert with respect to, i.e., does not substantially react chemically with, the polymer and has a temperature lower than the demixing temperature. In this way, a liquid-liquid phase separation is initiated and, on further cooling, the thermoplastic polymer solidified to form the membrane structure.
The membranes in accordance with DE-A-28 33 493 have an open-pored, microporous structure and also open-pored, microporous surfaces. On the one hand, this has the result that, in gas exchange processes, gaseous substances such as oxygen (O2) or carbon dioxide (CO2) can pass through the membrane relatively unrestricted and the transport of a gas takes place as a “Knudsen flow” combined with relatively high transfer rates for gases or high gas flow rates through the membrane. Such membranes with gas flow rates for CO2 exceeding 1 ml/(cm2*min*bar) and for O2 at approximately the same level have gas flow rates that are sufficiently high for oxygenation of blood.
On the other hand, in extended-duration use of these membranes in blood oxygenation or generally in gas exchange processes with aqueous liquids, blood plasma or a portion of the liquid can penetrate into the membrane and, in the extreme case, exit on the gas side of the membrane, even if in these cases the membranes are produced from hydrophobic polymers, in particular polyolefins. This results in a drastic decrease in gas transfer rates. In medical applications for blood oxygenation, this is termed plasma breakthrough.
The plasma breakthrough time of such membranes as producible in accordance with DE-A-28 33 493 is sufficient in most cases of conventional blood oxygenation to oxygenate a patient in a normal open-heart operation. However, these membranes are not suitable for so-called extended-duration oxygenation due to their relatively short plasma breakthrough times. Such membranes also cannot be used for gas separation tasks due to their consistent open-pored structure.
However, in the field of oxygenation, the desire exists for membranes with higher plasma breakthrough times in order to attain higher levels of safety in extended-duration heart operations and to rule out the possibility of a plasma breakthrough that would require immediate replacement of the oxygenator. The aim is also to be able to oxygenate premature infants or in general patients with temporarily restricted lung function long enough until the lung function is restored, i.e., to be able to conduct extended-duration oxygenation. A prerequisite for this is appropriately long plasma breakthrough times. A frequently demanded minimum value for the plasma breakthrough time in this connection is 20 hours.
From EP-A-299 381, hollow-fiber membranes for oxygenation are known that have plasma breakthrough times of more than 20 hours, i.e., there is no plasma breakthrough even under extended use. This is achieved with the otherwise porous membranes by using a barrier layer with an average thickness not exceeding 2 μm and substantially impermeable to ethanol. According to the disclosed examples, the membranes in accordance with EP-A-299 381 have a porosity of at most 31% by volume, since at higher porosity values the pores are interconnected via the membrane wall and communication occurs between the sides of the hollow-fiber membranes, resulting in plasma breakthrough.
The production of these membranes is conducted via a melt-drawing process, i.e., the polymer is first melt-extruded to form a hollow fiber and then hot- and cold-drawn. In this case, only relatively low porosity values are obtained, which means that, in conjunction with the transport occurring in the barrier layer via solution diffusion, the attainable transfer rates for oxygen and carbon dioxide remain relatively low. Moreover, while the hollow-fiber membranes in accordance with EP-A-299 381 exhibit sufficient tensile strength as a result of the pronounced drawing in conjunction with manufacture, they have only a small elongation at break. In subsequent textile processing steps, such as producing hollow-fiber mats, which have proven excellent in the production of oxygenators with good exchange capacity and as are described in EP-A-285 812, for example, these hollow-fiber membranes are therefore difficult to process.
U.S. Pat. No. 4,664,681 discloses polyolefin membranes in particular for gas separation, with a microporous layer and a non-porous separation layer, the membranes also being produced using a melt-drawing process. The properties of these membranes are similar to those described in EP-A-299 381.
Typically, in melt-drawing processes, membranes are formed with slit-shaped pores with pronounced anisotropy, the first main extension of which is perpendicular to the drawing direction and the second main extension perpendicular to the membrane surface, i.e., in the case of hollow-fiber membranes runs between the exterior and interior surfaces of the membrane, so that the channels formed by the pores run in a relatively straight line between the surfaces. In the case in which, for example, mechanical damage in the spinning process causes leaks in the barrier layer, a preferred direction then exists for the flow of a liquid between the interior and exterior surfaces or vice versa, thereby promoting plasma breakthrough.
DE-C-27 37 745 relates to microporous bodies likewise produced using a process with thermally induced liquid-liquid phase separation. During production of the microporous bodies, when the polymer solution is cast onto a substrate, such as a metal plate, the microporous bodies according to DE-C-27 37 745 can also exhibit a surface skin with a structure not having a cellular form, the thickness of the skin being in most cases approximately the thickness of an individual cell wall. DE-C-27 37 745, however, does not state that such microporous bodies with a surface skin are usable for gas exchange processes, in particular extended-duration oxygenation, or for gas separation processes. Moreover, hollow-fiber membranes cannot be produced using the procedure described in DE-C-27 37 745.
In WO 00/43113 and WO 00/43114, integrally asymmetrical polyolefin membranes are disclosed, and processes for producing them described, that are usable for gas exchange, in particular extended-duration oxygenation, or also for gas separation. The processes are likewise based on a thermally induced phase separation process with liquid-liquid phase separation. The membranes according to WO 00/43113 or WO 00/43114 have a support layer with a sponge-like, open-pored, microporous structure and, adjacent to on this support layer on at least one of the surfaces a separation layer with a denser structure. To produce this membrane structure, and in particular the separation layer, the cited specifications for producing the polyolefin solutions employed start with solvent systems consisting of a mixture of a solvent with a non-solvent for the polyolefin, where the properties of the solvent and non-solvent must meet specific requirements. A disadvantage of the processes disclosed in these specifications is that solvent systems must always be used that are mixtures of several components. Such solvent systems are, from experience, complex with respect to the elements of the process that are aimed at reusing the individual components.