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Hollow Fiber Membrane For Use in an Anesthetic Circuit

20190091626 ยท 2019-03-28

    Inventors

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    International classification

    Abstract

    Hydrophobic poly(4-methyl-1-pentene) hollow fiber membrane for retention of anesthetic agents with an inner and an outer surface and between inner and outer surface an essentially isotropic support layer with a sponge-like, open-pored, microporous structure free of macrovoids and adjacent to this support layer on the outer surface a dense separation layer with a thickness between 1.0 and 3.5 ?m. The membrane has a porosity in the range of greater than 35% to less than 50% by volume and a permeance for CO.sub.2 of IN 20-60 mol/(h.Math.m.sup.2.Math.bar), a gas separation factor ?(CO.sub.2/N.sub.2) of at least 5 and a selectivity CO.sub.2/anesthetic agents of at least 150. The process of for producing this membrane is based on a thermally induced phase separation process in which process a homogeneous solution of a poly(4-methyl-1-pentene) in a solvent system containing components A and B is formed, wherein component A is a strong solvent and component B a weak non-solvent for the polymer component. After formation of a hollow fiber the hollow fiber is cooled in a liquid cooling medium to form a hollow fiber membrane. The concentration of the polymer component in the solution may be in the range from 42.5 to 45.8 wt.-% and the hollow fiber leaving the die runs through a gap between die and cooling medium with a gap length in the range of 5-30 mm.

    Claims

    1. Integrally asymmetrical hydrophobic hollow fiber membrane for retention of anesthetic agents, which membrane is composed primarily of a poly(4-methyl-1-pentene) and has an inner surface facing towards its lumen, an outer surface facing outwards, a support layer with a sponge-like, open-pored, microporous structure between inner surface and outer surface and adjacent to this support layer on the outer surface a separation layer with denser structure, wherein the support layer is free of macrovoids and the pores in the support layer are on average essentially isotropic, characterized in that the separation layer has a thickness in the range between 1.0 and 3.5 ?m and, that the membrane has a permeance for CO2 of 20-60 mol/(h.Math.m.sup.2.Math.bar), a gas separation factor ?(CO2/N2) of at least 5 and a selectivity CO2/anesthetic agents of at least 150 and that the membrane has a porosity in the range of greater than 35% to less than 50% by volume.

    2. Membrane according to claim 1, characterized in that the membrane structure changes abruptly in the transition from the separation to the support layer.

    3. Membrane according to claim 1, characterized in that the separation layer has a thickness between 1.0 ?m and 2.0 ?m.

    4. Membrane according to claim 1, characterized in that the membrane has a permeance for CO2 of 25-40 mol/(h.Math.m.sup.2.Math.bar).

    5. Membrane according to claim 1, characterized in that the membrane has a permeance for CO2 of 25-40 mol/(h.Math.m.sup.2.Math.bar) and an 02 permeance of at least 10 mol/(h.Math.m.sup.2.Math.bar).

    6. Membrane according to claim 1, characterized in that it has a selectivity CO2/anesthetic agents of at least 220.

    7. Membrane according to claim 1, characterized in that it has a selectivity CO2/anesthetic agents of at least 400.

    8. Membrane according to claim 1, characterized in that it has a gas separation factor ?(CO2/N2) of at least 8.

    9. Process for producing an integrally asymmetrical hydrophobic hollow fiber membrane according to claim 1, the process comprising at least the steps of: a) preparing a homogeneous solution of a polymer component consisting of a poly(4-methyl-1-pentene) in a solvent system containing a component A and a component B that are liquid and miscible with each other at the dissolving temperature, whereby the employed mixture of the polymer component and components A and B has a critical demixing temperature and a solidification temperature and has a miscibility gap in the liquid state of aggregation below the critical demixing temperature, whereby a strong solvent for the polymer component is selected for component A, for which the demixing temperature of a solution of 25% by weight of the polymer component in this solvent is at least 10% below the melting point of the pure polymer component, wherein demixing temperature and melting point are measured in ? C., and component B raises the demixing temperature of a solution consisting of the polymer component and component A, wherein component B is a weak non-solvent for the polymer component, which does not dissolve the polymer component to form a homogeneous solution when heated to the boiling point of component B and for which the demixing temperature of a system consisting of 25% by weight of the polymer component, 10% by weight of the weak non-solvent, and 65% by weight of component A, used as the solvent, is at most 10% above the demixing temperature of a system consisting of 25% by weight of the polymer component and 75% by weight of component A, wherein the temperatures are measured in ? C., b) rendering the solution to form a hollow fiber, with outer and inner surfaces, in a die having an exit surface and a die temperature above the critical demixing temperature, c) cooling of the hollow fiber using a liquid cooling medium having an entrance surface, which cooling medium does not dissolve the polymer component or react chemically with it at temperatures up to the die temperature and is tempered to a cooling temperature below the solidification temperature, wherein the cooling medium is a homogeneous, single-phase liquid at the cooling temperature and the cooling is done at such a rate that a thermodynamic non-equilibrium liquid-liquid phase separation into a high-polymer-content phase and a low-polymer content phase takes place and solidification of the high-polymer-content phase subsequently occurs when the temperature falls below the solidification temperature, d) possibly removing components A and B from the hollow fiber, characterized in that the concentration of the polymer component in the homogeneous solution is in the range from 42.5 to 45.8% by weight and the concentration of the solvent system in the range from 57.5 to 54.2% by weight and that the hollow fiber leaving the die runs through a gap between the exit surface of the die and the surface of the cooling medium before entering the cooling medium, wherein the gap has a length in the range of 5-30 mm.

    10. Process according to claim 9, characterized in that the cooling medium is a liquid that is a strong non-solvent for the polymer component, for which the demixing temperature of a system consisting of 25% by weight of the polymer component, 10% by weight of the strong non-solvent, and 65% by weight of component A, used as a solvent, is at least 10% higher than the demixing temperature of a system consisting of 25% by weight of the polymer component and 75% by weight of component A.

    11. Process according to claim 9, characterized in that the concentration of the polymer component in the homogeneous solution is in the range of 43-45.5% by weight and the concentration of the solvent system in the range of 57-54.5% by weight.

    12. Process according to claim 9, characterized in that dioctyl adipate, isopropyl myristate, diphenyl ether, dibenzyl ether, or a mixture thereof is used as component A.

    13. Process according to claim 9, characterized in that glycerin triacetate, diethyl phthalate, castor oil, N,N-bis(2-hydroxyethyl)tallow amine, soybean oil, or a mixture thereof is used as component B.

    14. Process according to claim 12, characterized in that dioctyl adipate is used as component A.

    15. Use of a membrane according to claim 1 in an anesthetic circuit.

    Description

    [0078] Permeation characteristics of the membranes in the modules were measured using a variation of the constant-pressure variable-volume method.

    [0079] FIG. 1 shows a schematic of the experimental system.

    [0080] The feed gas flow rate was controlled using a needle valve and flow was measured using a glass tube flow meter (Scott Specialty Gases, Plumsteadville, Pa., USA) and the feed pressure using an analogue pressure gauge (Speidel Keller, Jungingen, Germany, accuracy: ?5 mmHg or ?6.67 mbar) connected to the lumen outlet stream. The feed pressure on the lumen side was held constant at 1.2 bar for each experiment. The permeate pressure on the shell side was atmospheric. One port of the shell side of the module was plugged and the other port was fed through a 3-way valve either to a modified, horizontally placed glass pipette (Fischer Scientific, 5 mL total volume) for flow measurements or to the mass spectrometer for concentration determination.

    [0081] To calculate the mean flow rate, the pipette was filled with water prior to each trial and time measurements were taken at 0.5 mL intervals as the permeated gas displaced the water. Immediately following the volumetric flow rate measurement, the permeate was then fed to the mass spectrometer sampling port and the gas composition only for the mixed gas experiments. Feed gas concentrations were measured when both shell-side ports on the module were plugged. The gas composition was measured from the retentate port of the module. The system was purged with oxygen between each trial.

    Pure Gas Permeation Measurements

    [0082] The pure gas permeance of the membranes was determined for pure carbon dioxide (CO.sub.2), oxygen (O.sub.2), and nitrogen (N.sub.2) supplied at 1.2 bar. Once the concentration of the gases stabilized, the permeate line was connected to the pipette setup. Four time readings were then measured every 0.5 mL as the permeate displaced the water. These readings were averaged and counted for one trial. A minimum of three trials were performed for each module at each set of operating conditions. A minimum of three trials were performed for each module at each set of operating conditions. The pure gas permeance was calculated according to Equation 7:

    [00006] K i P = Q A ? ( p f - p p ) ( 7 )

    [0083] Where Q is the permeate molar flow rate (mol/h), p.sub.f is the absolute pressure of the feed (bar), p.sub.p is the absolute pressure of the permeate (bar), and A is the inside active membrane area (m.sup.2). Permeance is reported in units of mol/h/m.sup.2/bar. The pure gas selectivity (4) was calculated based on the ratio of the mean permeance of two pure gases i and j per Equation 8:

    [00007] ? ij P = K i P K j P ( 8 )

    Where K.sub.i.sup.P and K.sub.j.sup.P are the pure gas permeances for components i and j, respectively.

    Mixed Gas Permeation Measurements

    [0084] The mixed gas permeation procedure was similar to that of the pure gas system but also required concentration measurements of the permeate. The feed and retentate compositions were determined as described above. In addition, following the flow measurements, the permeate was directed to the mass spectrometer for determination of the permeate composition.

    [0085] Anaesthetic vapour concentrations for the experiments were chosen around their Minimum Alveolar Concentration (MAC). The MAC is a measure of potency of the anaesthesia gas and is defined as the minimum concentration of vapour required to immobilize 50% of patients. The MAC for Sevoflurane, Desflurane and Isoflurane is defined as 2.13%, 6.0% and 1.13% respectively. The vapour experiments were conducted with vapour concentrations at the MAC for each vapour. This set of experiments was performed near clinically relevant operating conditions, at room temperature and low feed pressure (1.2 bar) with either Sevoflurane, Isoflurane or Desflurane at their MAC mixed into a 5% carbon dioxide/oxygen gas mixture to mimic exhalation during anaesthesia administration. Three modules of each membrane type were used and three runs of each module were performed for a total of n=9 trials for Sevoflurane, Isoflurane and Desflurane.

    [0086] The mixed gas tests entailed monitoring the feed, retentate and permeate gas composition with the mass spectrometer, in addition to the flow rate. The permeances of the mixed gas components were calculated using Equation 9:

    [00008] K i M = y p .Math. Q A .Math. .Math. ? .Math. .Math. p i , ave ( 9 )

    [0087] The log-mean driving force (Equation 4) was used to compute ?P.sub.i,ave. The mixed gas selectivity, alpha.sup.M, was calculated using the permeance of two components i and j in a gas mixture per Equation 10:

    [00009] ? ij M = K i M K j M ( 10 )

    [0088] Examples 1 to 3 and Comparative Examples 1a, 1 b, 2 and 3: In the Examples 1 to 3 and the Comparative Examples 1a, 1 b, 2 and 3, the membranes were manufactured according to the following procedure:

    [0089] Poly(4-methyl-1-pentene) (TPX DX845) as polymer component was dissolved in a nitrogen atmosphere in a container with stirrer at a temperature of 260? C. in a solvent system consisting of 70% by weight dioctyl adipate, 20% by weight glycerin triacetate, and 10% by weight castor oil. The concentrations of polymer and solvent system used in Examples 1 to 3 and in Comparative Examples 1a, 1b, 2 and 3 are listed in Table 1.

    [0090] After degassing, the resulting clear and homogeneous solution was fed with a gear pump to a hollow-fiber die with an annular-gap outside diameter of 1.2 mm, which had been heated to 248? C., and extruded to form a hollow fiber. Nitrogen was metered into the lumen of the hollow fiber through the interior bore of the hollow-fiber die. After an air section of 24 mm, the hollow fiber passed through an approx. 1 m long spinning tube, through which glycerin triacetate, tempered to ambient temperature, flowed as a cooling medium. The hollow fiber, solidified as a result of the cooling process in the spinning tube, was drawn off from the spinning tube at a rate of 72 m/min, wound onto a spool, subsequently extracted with isopropanol, and then dried at approx. 120? C.

    [0091] Hollow-fiber membranes were obtained with an inner diameter of about 200 ?m and a wall thickness of about 90 ?m, for which no pores were observable on its exterior surface in a scanning-electron-microscopic (SEM) image even at 60000? magnification. The interior surface facing the lumen had an open-pored, network-like structure with approximately circular openings. The sponge-like, open-pored, microporous support structure is covered by an approx. 1.5-2.0 ?m thick separation layer.

    TABLE-US-00002 TABLE 1 Comp. Comp. Exampl. Exampl. Exampl. Comp. Comp. Membrane Ex. 1a Ex. 1b 1 2 3 Ex. 2 Ex. 3 Polymer concentr. (wt. %) 46.0 46.0 45.8 45.5 45.0 42.5 41.0 Solvent system concentr. (wt. %) 54.0 54.0 54.2 54.5 55.0 57.5 59.0 Solvent system/polymer 1.17 1.17 1.18 1.20 1.22 1.35 1.44 ratio Fiber wall thickness (?m) 90 90 90 90 90 90 90 Fiber internal diameter (?m) 200 200 200 200 200 200 200 Active inside area module (cm.sup.2) 24 26 26 26 26 26 26 Active outside area module (cm.sup.2) 45 49 49 49 49 49 49 Module filling degree % 20.00 20.06 20.06 20.06 20.06 20.06 20.06

    [0092] With the membranes of each example and comparative example test modules were prepared for testing the properties of the membranes. For this purpose, a minimum of three modules of each membrane type was produced by arranging the hollow fiber membranes in a cylindrical housing and potting the ends of the hollow fiber membranes in tube shells made from polyurethane. The lumina of the hollow fiber membranes were in fluid connection with a feed inlet and a feed outlet, respectively. The space in the module surrounding the hollow fiber membranes was in fluid connection with a permeate outlet.

    [0093] Details of the membrane modules are listed in Table 2.

    [0094] For the membranes of each example and comparative example the permeance for CO.sub.2, O.sub.2, and N.sub.2, the gas separation factor ?(CO.sub.2/N.sub.2) and the selectivity CO.sub.2/anesthetic agents was measured according to the test methods described above.

    [0095] The pure gas permeances for carbon dioxide (CO.sub.2), oxygen (O.sub.2) and nitrogen (N.sub.2) are listed in Table 3 and are shown in FIG. 2. The property of most interest for the intended application is the carbon dioxide permeance. In addition, the permeabilities of the three gases are presented in Table 2 for the examples and the comparative examples, wherein the permeabilities are calculated on the basis of the respective permeances by multiplying the permeances by the membrane thickness (fiber wall thickness=90 ?m).

    TABLE-US-00003 TABLE 3 K.sub.i P.sub.ip (mol/m.sup.2/bar/h) (10.sup.3 mol cm/m.sup.2/bar/h) Selectivity ?.sub.ij CO.sub.2 N.sub.2 O.sub.2 CO.sub.2 N.sub.2 O.sub.2 CO.sub.2/O.sub.2 O.sub.2/N.sub.2 CO.sub.2/N.sub.2 Example 1 23.1 1.6 10.7 208 14 96 2.2 6.9 15.0 Example 2 32.3 3.0 12.3 291 27 111 2.6 4.2 10.9 Example 3 31.8 2.7 14.9 286 24 134 2.1 5.7 12.1 Comp. Ex. 1a 16.7 2.3 7.1 150 21 64 2.3 3.1 7.2 Comp. Ex. 1b 19.8 1.7 7.8 178 15 71 2.5 4.6 11.5 Comp. Ex. 2 88.6 10.1 36.4 797 91 328 2.4 3.6 8.8 Comp. Ex. 3 110.9 10.6 42.2 998 95 380 2.6 4.0 10.5

    [0096] For the membranes of each example and comparative example mixed gas experiments were performed, i.e. experiments with gas mixtures containing either Sevoflurane (2.0 Vol.-%), Isoflurane (6.13 Vol. %), or Desflurane (1.13 Vol. %) with a balance of 5 Vol. % CO.sub.2 in O.sub.2 and the CO.sub.2 permeance, K.sub.CO2 (in (mol/m.sup.2/bar/h)), in these mixtures was compared to the permeance K.sub.CO2 of pure CO.sub.2 as determined in the pure gas experiments (see above). The results obtained are listed in Table 4 and shown in FIG. 3.

    TABLE-US-00004 TABLE 4 K.sub.CO2 K.sub.CO2 K.sub.CO2 K.sub.CO2 (CO.sub.2/ (CO.sub.2/ (Pure CO.sub.2) (CO.sub.2/O.sub.2/Sevo) O.sub.2/Iso) O.sub.2/Des) Example 1 23.1 15.8 Example 2 32.3 33.1 11.4 25.2 Example 3 31.8 23.9 10 40.5 Comp. Example 1a 16.7 10.4 5.3 10.1 Comp. Example 1b 19.8 18.4 7.6 16.6 Comp. Example 2 88.6 63.3 Comp. Example 3 110.9 86

    [0097] In Table 5 the selectivity of CO.sub.2 over Servoflurane as obtained from the mixed gas experiments is listed together with the pure CO.sub.2 permeance for hollow fiber membranes of Examples 1 to 3 and Comparative Examples 1 to 3. Sufficiently high selectivities CO.sub.2/Servoflurane resulting in a good retention of anesthetic gases by the membranes with at the same time sufficiently high permeances for CO.sub.2 are obtained for the membranes of Examples 1 to 3. FIG. 4 shows a diagram of the selectivity CO2/Servoflurane in dependency of the pure CO.sub.2 permeance.

    TABLE-US-00005 TABLE 5 Pure CO.sub.2 Solvent system/ Permeance Selectivity ?.sub.ij polymer ratio (mol/m.sup.2/bar/h) CO.sub.2/Sevoflurane Example 1 1.18 23.1 1130 Example 2 1.20 32.3 550 Example 3 1.22 31.8 250 Comp. Example 1a 1.17 16.7 1450 Comp. Example 2 1.35 88.6 86 Comp. Example 3 1.44 110.9 93

    [0098] FIG. 5 plots the CO.sub.2/Sevoflurane selectivity as a function of the CO.sub.2 permeance for the Examples and Comparative Examples listed in Table 5.

    [0099] This patent application filing claims priority to European patent application number EP 16166434.7 filed on Apr. 21, 2016, the specification having numbered pages 1-45 and FIGS. 1-10 on drawing sheets 1-6, the disclosure of which is herein incorporated by reference in its entirety.