KR101573968B1 - A method for preparation of enantioselective composite membrane - Google Patents

Abstract

The present invention provides an enantioselective composite membrane useful for the separation of optical isomers and a process for preparing the same. The present invention further provides a membrane-based pressure-driven separation method for separating enantiomers from a mixture of enantiomers to produce optically pure isomers. The present invention also provides a membrane-based method for the optical resolution of a racemic mixture of amino acids to obtain optically pure amino acids.

Description

TECHNICAL FIELD The present invention relates to a method for preparing a mirror-

The present invention relates to a process for preparing an enantioselective composite membrane for the separation of amino acids from aqueous solutions of amino acids and the optical resolution of racemic mixtures. The present invention is particularly directed to a process for preparing an enantioselective complex nanofiltration membrane useful for the separation of optical isomers of amino acids.

The inventive enantioselective composite membranes are useful for separating enantiomers from mixtures of enantiomers to give optically pure isomers. The inventive mirror-selective composite membranes can be used to optically decompose racemic mixtures of amino acids and chiral compounds to obtain optically pure enantiomers in pressure-driven membrane processes such as reverse osmosis, nanofiltration, and the like.

Stereoisomers are molecules in which only the arrangement of atoms in space is different from each other. Stereoisomers are generally categorized as diastereomers or enantiomers, the latter including those which are mirror images of one another, and the former is not mirror image. Enantiomers (enantiomers), also known as optical isomers, have the same physical and chemical properties. Thus, in principle, mixtures of enantiomers can not be separated by conventional separation methods, for example fractional distillation (boiling points are the same), and if the solvent is not optically active, conventional crystallization or (due to the same solubility) Can not be separated by conventional chromatography (equally fixed for a conventional adsorbent) unless it is optically active. The problem of separation of enantiomers is exacerbated by the fact that conventional synthetic techniques almost always produce mixtures of enantiomers. Thus, separation of mixtures of enantiomers is the most challenging task in analytical chemistry.

The separation of enantiomers is very important for organic compounds such as amino acids, drugs, insecticides, pesticides and the like because most of them are optically active and exist as pairs of optical isomers (enantiomers). The enantiomers of many chiral drugs differ markedly in terms of their biological and pharmacological properties. One enantiomer may have drug activity, while the other may be inert or even harmful. For example, (S) -verapamil is effective as a calcium channel blocker, but (R) -verapamil causes heart disease side effects. (-) - enantiomer of the .beta.-blocker propranolol is about 100-fold more active than the d-form, while the (R) (+) - enantiomer of the thalidomide contains sleeping action, The isomerism involved teratogenic effects, and differences in the pharmacological action of thalidomide were found to cause severe deformities in neonates of women taking the drug during pregnancy (ie, the "thalidomide tragedy" of the 1960s, etc.) . Thus, the United States Food and Drug Administration has recently enacted new legislation covering the market for chiral drugs. According to the new regulation, the pharmacological properties of each enantiomer of a chiral drug must be tested separately for therapeutic effect and stability.

Various methods for separating enantiomers are known, such as diastereomerisation, enzyme catalyzed reactions, chromatographic methods, application of liquid membranes, molecular recognition techniques, and inclusion complexation techniques . Preferred crystallization, partial-parent isomer decomposition, enzyme catalyzed reactions, etc. include coupling of enantiomers and auxiliary chiral reactants which convert these into diastereoisomers which are separable by conventional separation techniques which will be described hereinafter. Looking at the diastereomeric degradation, it is described in "CRC Handbook of Optical Resolutions via Diasteromeric Salt Formation" Kozma D., 2002 ISBN: 0849300193. A major disadvantage of diastereomeric degradation is the large amount of optically pure derivatizing agents (chiral reagents or solvents) that are expensive and often not recoverable.

Chromatography (GC, HPLC, CE, etc.) is described in Chiral Separation Techniques - A Practical Approach, Second Edition, edited by G. Subramanian ISBN 3-527-29875-4, The method of the present invention requires a suitable chiral selector which can be introduced as a fixed bed (chiral stationary phase) or coated on the surface of a column packing material (chiral coated stationary phase). An enantioselective chiral column with a chiral stationary phase is expensive and has a limited working life. Therefore, the separation cost is very high.

A review of the molecular recognition phenomenon for enantiomeric separation can be found in Chiral Separation Techniques - A Practical Approach, Second Edition, Edited by G. Subramanian ISBN 3-527-29875-4. A]. Many chiral stationary phases, complexes, and the like have been developed based on molecular recognition.

Referring to U. S. Patent No. 6,759, 488 entitled " Molecular Imprinted Polymer (MIP) Grafted on a Solid Support, " the separation of enantiomers is based on molecular recognition. A disadvantage of the MIP technique is that only crosslinkable monomers can be used to produce molecular imprinting membranes.

In U. S. Patent No. 5,080, 795 entitled " Supported Chiral Liquid Membranes for Enantiomeric Isomerization, " the chiral carrier-containing supported chiral liquid membranes selectively form complexes with one of the two enantiomers, Separate this. The main disadvantage of the film is poor stability and loss of enantioselectivity over time.

U.S. Patent No. 6,485,650 entitled "Liquid Separation of Enantiomers" describes a method for separating enantiomers in a supported liquid membrane module containing a feed fluid containing a racemic mixture and a carrier and a phase transfer agent Comprises moving the enantiomer to the liquid membrane, and then contacting the liquid membrane with a sweep fluid. This enantiomer is then recovered from the sweep fluid. The membrane module is configured in such a manner that the feed fluid and the sweep fluid are adjacent to the liquid film but on the opposite side of the liquid surface, and the feed and sweep fluid are substantially continuously in contact with each other along the length of the liquid film. A drawback of the liquid-liquid extraction technique is the low productivity and the possibility of intermixing of the two solutions at the membrane interface.

The aromatic polyamide film is an interfacial reaction product of an aromatic polyamine having at least two primary amine groups and an aromatic acyl halide having at least three acyl halide groups, as disclosed in U.S. Patent No. 4,277,344 titled " Interfaced Synthetic Reverse Osmosis Membrane ". According to this patent, the porous polysulfone support is coated with m-phenylene diamine in water. After removing excess m-phenylenediamine from the coated support, the coated support is covered with a solution of trimethoyl chloride dissolved in a " FREON "TF solvent (trichlorotrifluoroethane). The contact time of the interfacial reaction is 10 seconds, and the reaction is substantially completed in 1 second. Then, the resulting polysulfone / polyamide composite membrane is air-dried. The membrane is claimed to exert excellent flux and salt removal capabilities. However, in order to improve the film performance, various types of additives are introduced into the solution used in the interfacial polycondensation reaction. The disadvantage of this film is that it has no mirror image selectivity.

U.S. Patent No. 5,205,934 entitled " Silicone Derived Solvent Stable Membrane "describes a process for preparing a composite nanofiltration membrane comprising a support, preferably a silicon layer immobilized on a polyacrylonitrile support. Such composite membranes are solvent stable and claimed to be useful for separating high molecular weight solutes, such as organo metallic catalyst complexes, from organic solvents. The film does not possess enantioselectivity.

In U.S. Patent No. 6,743,373 entitled " Enantiopure Separation and Enantiopure Reagents ", the mixture comprising an enantiomer is reacted with an optically active amino acid-based reagent in a basic medium, and the resultant diastereomer Is applied to the separation process. A disadvantage of this process is that, for the separation of the enantiomers, the enantiomers must have at least one free functional group, the reagents are amino acids having an active group such that at least one carboxyl group of the amino acid is substituted and the active precursor of the isocyanate group is formed Of at least one amino group.

As described above, the enantioselective polymer membranes described in the prior art are asymmetric high dense membranes made from chiral polymers such as polysaccharides and derivatives, poly-alpha-amino acids, polyacetylene derivatives and the like. Most such polymers are crystalline in nature and do not have membrane forming ability. Therefore, a film made from such a polymer is liable to be damaged and is difficult to handle. Poor mechanical properties limit its use to dialysis separation. In the separation of the dialysis system, the propulsive force is merely a solute concentration gradient, and this film exhibits a very low transmittance. Other types of enantiomeric separation membranes are prepared from non-chiral polymers with branched enantiomeric recognition molecules, i. E., Amino acids, proteins, oligo-peptides, and the like. However, although these membranes have excellent mechanical properties, the recognition sites are saturated during permeation and are rapidly immobilized in the polymer matrix, and the selectivity of such membranes decreases rapidly over time.

Composite membranes are typically prepared by coating a porous support membrane with an aqueous solution of a polyfunctional amine and then coating the solution with a solution of a polyfunctional acyl halide in an organic solvent to form an interfacial pivot between the polyfunctional amine and the polyfunctional acyl halide, For example, by preparing a discriminating layer of polyamide by sum-of-charge reaction.

The inventive step involved in the present invention is characterized in that (i) a composite film layer is formed by interfacial polymerization of a polyfunctional acyl chloride with a polyfunctional amine and a chiral amine, (ii) the production of a chiral enantioselective layer by an interfacial method (Iii) the process minimizes the need for an optically pure chiral reagent, which is essential for the resolution of the racemic mixture, and (iv) the use of an optically pure chiral reagent, The process produces a chiral microenvironment of the polymer membrane in the form of an enantioselective thin film supported on the ultrafiltration layer, resulting in high flux and high selectivity.

It is a principal object of the present invention to provide a process for the production of self-supporting and perm-selective membranes for enantiomer separation by pressure-driven membrane processes, such as reverse osmosis, nanofiltration, will be.

It is a further object of the present invention to provide a composite membrane based on piperazine and triisooyl chloride that is non-enantiomeric and thus fails to separate enantiomers.

It is still another object of the present invention to provide a high stability and retention of mirror image selectivity over time.

It is a further object of the present invention to provide a process for preparing an enantioselective complex nanofiltration membrane for separating enantiomers of chiral molecules.

It is a further object of the present invention to provide a membrane-based method for optically resolving a racemic mixture into optically pure isomers.

Figure 1 shows the ATR-FTIR spectrum for the chemical structure of an enantioselective layer of an enantioselective composite membrane.

Accordingly, the present invention provides a process for preparing an enantioselective composite membrane useful for separating an enantiomer from a mixture of enantiomers to obtain optically pure isomers,

(a) providing an ultrafiltration (UF) membrane produced by a wet phase inversion method;

(b) filtering the ultrafiltration membrane obtained from step (a) with 1 to 2% by weight aqueous solution of a mixture of amino acids or amino acids, polyfunctional amines and acid acceptors for 1 to 5 minutes, maintaining the pH between 10 and 13 Dip coating with a mixture comprising;

(c) withdrawing the coated UF membrane from the mixture obtained from step (b) and draining the extra solution from the UF membrane for 5 to 30 minutes;

(d) immersing the coated membrane obtained from step (c) in a 0.1 to 1 wt% solution of triacyl halide in hexane for 1 to 5 minutes and evacuating the excess solution for 1 to 5 minutes;

(e) drying the membrane obtained in step (d) for 1 to 4 hours;

(f) heating the membrane obtained in step (e) to a temperature of 70 to 100 DEG C for 1 to 15 minutes, followed by cooling and air drying for 1 to 2 hours;

(g) immersing the membrane obtained in step (f) in deionized water for up to 24 hours to obtain an enantioselective composite membrane comprising an enantioselective layer on the ultrafiltration membrane and testing it for separation of the amino acid from the aqueous amino acid solution

The method comprising the steps of:

In an embodiment of the present invention, the thickness of the mirror selective layer of the composite film used ranges from 400 to 1600 ANGSTROM.

In another embodiment of the present invention, the amino acid or mixture of amino acids used is selected from the group consisting of two or more primary amino groups.

In another embodiment, the enantioselective layer of the composite membrane used is a crosslinked polyamide polymer having at least one chiral carbon atom.

In another embodiment, the multifunctional amine used is selected from metaphenylene diamine and piperidine, and the acid acceptor used is selected from triethylamine and NaOH.

In another embodiment, the multifunctional triacyl halide used is trimesoyl chloride.

In another embodiment, the ultrafiltration membrane used is selected from polysulfone, polyethersulfone, and polyvinylidene fluoride having a thickness in the range of 20 to 60 占 퐉.

In another embodiment, the enantioselective composite membrane separates 50-70% arginine and 80-90% lysine from the aqueous solution.

In another embodiment, an enantiomeric separation method of a racemic mixture of amino acids using an enantioselective composite membrane is carried out in a reverse osmosis membrane test unit under trans membrane pressure in the range of 345 to 862 KPa, Is carried out using aqueous solutions and / or buffers of amino acids in the range of 0.1 to 1% by weight as feeds at a flow rate in the range of 800 ml / min.

In another embodiment, the concentration of amino acids in the permeate is measured by a UV-Vis spectrophotometer and the ratio of the d and 1-enantiomers in the permeate is determined by HPLC using a chiral column equipped with a PDA detector Lt; / RTI >

The optically-anisotropic thin film composite membrane of the present invention can be produced by mixing a microporous support with a basic amino acid (an amino acid having two or more primary amino groups, i.e. arginine, lysine) or a basic amino acid, a polyfunctional amine, Preferably with piperazine and an acid acceptor, triethylamine, NaOH, preferably NaOH, and then with a multifunctional acyl halide (with more than one reactivity), preferably with trimethoyl chloride, stepwise ≪ / RTI > The coating steps need not be in any particular order, but a mixture of amino acids, or amino acids, multifunctional amines and acid acceptors, is preferably coated first and then coated with a multifunctional acyl halide. Amino acid, or a mixture of an amino acid and a multifunctional amine is coated from an aqueous solution, and the multifunctional acyl halide is coated from the organic solution.

First, the ultrafiltration membrane is fabricated from a polymer material such as polysulfone, polyethersulfone, polyvinylidene fluoride and the like, preferably polysulfone by a phase inversion technique. In this technique, a solution of the desired polymer in an aprotic solvent such as dimethylformamide, N, N-dimethylacetic acid, etc. at a desired concentration of 12 to 18% by weight (more accurately, 18% Is sprayed onto a nonwoven polyester fabric (support) in a uniform thickness, and then after a specified time of 10 to 40 seconds, it is immersed in a coagulation bath containing a 2 wt% aqueous solution of dimethylformamide. The membrane is washed with deionized water for several hours.

The thus prepared ultrafiltration membrane preferably contains an amino acid or an amino acid (arginine), a polyfunctional amine, preferably piperazine (ratio of 50-50% arginine and piperazine) and an acid acceptor such as triethylamine and NaOH , An aqueous solution of 1 to 2% by weight of a mixture of NaOH was reacted to prepare a thin mirror-image selective layer in-situ on an enantioselective layer of an ultrafiltration membrane by an interfacial polymerization technique, It is used in the manufacture of nanofiltration membranes. The pH of the aqueous solution is maintained at 10 to 13, preferably 12, using 0.1 to 1% by weight of a solution of trimesoyl chloride in hexane.

In order to produce an enantioselective layer on the enantioselective layer of the ultrafiltration membrane, it is first reacted with an amino acid, or an amino acid, a multifunctional amine, preferably piperazine (ratio of 50-50% arginine and piperazine) Triethylamine, and NaOH, for 1 to 5 minutes, and for exactly 3 minutes. The coated UF membrane is removed from the solution and the excess solution is drained from the UF membrane for about 5 to 30 minutes, preferably 15 minutes, to retain the desired amount of monomer.

The UF membrane is then dip-coated with a solution of 0.1 to 1 wt.%, Preferably 0.5 wt.% Of trimesoyl chloride in hexane for from about 1 to 5 minutes, for exactly 3 minutes. The resulting coated UF membrane is removed from the tri-mesochloride solution mixture and drained for 1 to 5 minutes, preferably 5 minutes, from the membrane to remove excess tri-mesyl chloride solution. The film is then air dried for 1 to 4 hours, precisely 4 hours, and then cured by heating to a temperature of 70 to 100 占 폚, precisely 90 占 폚 for 1 to 15 minutes, precisely 10 minutes. The resulting film was then cooled, allowed to dry in air for 2 hours, and then soaked in water for 24 hours to obtain the desired optically active composite membrane.

Figure 1: An enantioselective composite membrane was characterized by an ATR-FTIR spectrophotometer for the chemical structure of its enantioselective layer. The ATR-FTIR spectra of the polysulfone membranes before and after coating were measured using a Perkin-Elmer spectrometer (Perkin-Elmer spectrometer) using germanium crystals at a nominal angle of incidence of 45 ° at a rate of 100 scans at a resolution of 2 cm ^-1 Spectra (Perkin-Elmer Spectrum GX, ATR-FTIR). The ATR-FTIR spectrum of (B) is shown below, after being coated in situ with a polysulfone membrane (A) and a poly (piperazine arginine trimesamide) film. The peaks at 1487 to 90 cm ^-1 , and 1584 cm ^-1 are characteristic of the polysulfone support. The appearance of the absorber band in the region of 1472 to 1644 cm ^-1 can be attributed to C = O, C = N stretching vibration. The peak at 1667 cm <" ¹ > in the spectrum of the coated film is an indication of amide formation. The characteristic absorption at 1731 cm ^-1 is C = O of the imide ring, the characteristic absorption at 1369 cm ^-1 is the CNC of the imide (in the plane), and the characteristic absorption at 747 cm ^-1 is Due to the CNC of the imide (out of plane bending).

The membrane can be used at a flow rate of 300 to 800 ml / min at a temperature of 25 占 폚, precisely at a flow rate of 500 ml / min, with a buffer aqueous solution of 0.1 to 1% by weight amino acid as a feed, at 345 to 862 KPa, The membrane penetration pressure of KPa was tested on a reverse osmosis membrane test unit for separation of these amino acids, preferably arginine, lysine, alanine and the like, from aqueous buffer solutions, and enantiomeric separation of the racemic mixture of amino acids. The concentration of the amino acid in the permeate was measured by a UV-VIs spectrophotometer at 290 nm and the ratio of the d- and l-enantiomers in the permeate for enantiomeric excess (ee%) was measured using a chiral column chrome pack +) (Chiral column Chrompack (+); supplied by Diacel Chemical Industries, USA).

Enantiomers are chiral molecules that have the same molecular and chemical structure but differ only in their spatial orientation. The difference in spatial coordination has many effects because the biological and pharmacological activities of many chiral compounds are completely different. Thus, the use of these compounds in optically pure form is imminent. There are complications in the separation of the enantiomers. Many techniques for separating enantiomers based on different techniques are known in the art. All mirror separation techniques are based on a chiral microenvironment near the racemic mixture to identify the paired enantiomers.

The presence of a homo-chiral environment is necessary to distinguish the paired enantiomers. The novelty of the membranes of the present invention is that they create a chiral microenvironment in the polymer membrane in the form of a thin layer of an enantioselective layer supported on the ultrafiltration layer, resulting in higher flux and higher selectivity.

The composite membrane of the present invention has an enantioselective layer chiral identification layer prepared in situ on an ultrafiltration membrane. The enantioselective layer identification layer is caused by interfacial polymerization of a multifunctional acyl chloride with a chiral amino acid and a multifunctional amine. The preparation of chiral enantioselective layers by the interfacial method requires very small amounts of chiral compounds and very broad membranes with a homo-chiral environment can be prepared. Thus, the need for optically pure chiral reagents essential for the resolution of the racemic mixture is minimized.

The following examples are provided by way of illustration and are not to be construed as limiting the scope of the invention.

Example 1

The enantioselective composite membrane was prepared by impregnating a polysulfone UF membrane with a 1 wt% aqueous solution of arginine and piperazine (50: 50) (the pH of the solution was maintained at 12 by adding 1 N NaOH) for 3 minutes, And the membrane was then immersed in a 0.5 wt% solution of trimethoyl chloride in hexane for 2 minutes, draining the excess solution for 2 minutes, and then drying the membrane for 4 hours in air. The film was heat cured at a temperature of 90 DEG C for 5 minutes, cooled to 25 DEG C, air dried for 2 hours, and dipped in deionized water for up to 24 hours. This membrane was tested for separation and enantioselectivity to arginine using a 0.1 wt% aqueous solution of racemic arginine as a feed at a flow rate of 55 ml / min under standard conditions at 500 ml / min. The membrane exhibited a permeation rate of 636 l / m ² / day and a rejection of 75% for arginine. The enantioselectivity for d-arginine was observed to be 65%.

Example 2

The enantioselective composite membrane was prepared by impregnating a polysulfone UF membrane with a 1 wt% aqueous solution of arginine and piperazine (50: 50) (the pH of the solution was maintained at 12 by adding 1 N NaOH) for 3 minutes, And then immersing the membrane in a 1 wt% solution of trimethoyl chloride in hexane for 2 minutes, draining the excess solution for 5 minutes, and then drying the membrane for 4 hours in air. The film was heat cured for 5 minutes at a temperature of 90 캜, cooled to 25 캜, air dried for 2 hours, and then dipped in deionized water for up to 24 hours. This membrane was tested for separation and enantiomeric selectivity to arginine using a 0.1 wt% aqueous solution of racemic arginine as a feed at 552 KPa at a flow rate of 500 ml / min under standard conditions. The membrane exhibited a permeation rate of 734 l / m ² / day and a removal rate of 66% after 6 hours for arginine. The enantioselectivity for d-arginine was observed to be 50%.

Example 3

The enantioselective composite membrane was prepared by impregnating the polysulfone UF membrane with a 1 wt% aqueous solution of piperazine (the pH of the solution was maintained at 12 by addition of 1N NaOH) for 3 minutes, draining the excess solution for 15 minutes, The film was prepared by immersing the membrane in 0.5 wt% solution of trimethoyl chloride in hexane for 2 minutes, draining the excess solution for 5 minutes, and then drying the membrane for 4 hours in air. The film was heat cured at a temperature of 90 DEG C for 5 minutes, cooled to 25 DEG C, air dried for 2 hours, and dipped in deionized water for up to 24 hours. This membrane was tested under standard conditions using a 0.1 wt% aqueous solution of racemic arginine as the feed at a flow rate of 552 KPa at a flow rate of 500 ml / min. The membrane exhibited a permeation rate of 1125 l / m ² / day and a removal rate of 60% for arginine. The membrane did not exhibit any enantioselectivity for d-arginine.

Example 4

The enantioselective composite membrane was prepared by impregnating the polysulfone UF membrane with a 1 wt% aqueous solution of arginine (the pH of the solution was maintained at 12 by adding 1 N NaOH) for 3 min, draining the excess solution for 15 min, The membrane was prepared by immersing the membrane in 0.5 wt% solution of trimethoyl chloride in hexane for 2 minutes, draining the excess solution for 2 minutes, and then drying the membrane for 4 hours in air. The film was heat cured at a temperature of 90 DEG C for 5 minutes, cooled to 25 DEG C, air dried for 2 hours, and dipped in deionized water for up to 24 hours. This membrane was tested under standard conditions using a 0.1 wt% aqueous solution of racemic arginine as the feed at a flow rate of 552 KPa at a flow rate of 500 ml / min. The membrane exhibited a permeation rate of 1125 l / m ² / day and a removal rate of 48% for arginine and the membrane exhibited a 50% mirrored selectivity for d-arginine.

Example 5

The enantioselective composite membrane was prepared by impregnating the polysulfone UF membrane with a 1 wt% aqueous solution of lysine and piperazine (50:50) for 5 minutes at pH 12, draining the excess solution for 15 minutes, By immersion in a 0.5% by weight solution of tri-mesoyl chloride, draining the excess solution for 5 minutes, and then drying the film for 4 hours in air. The film was heat cured at a temperature of 90 DEG C for 5 minutes, cooled to 25 DEG C, air dried for 2 hours, and dipped in deionized water for up to 24 hours. This membrane was tested under standard conditions using a 0.1 wt% aqueous solution of racemic lysine as the feed at a flow rate of 500 ml / min at 552 KPa. The membrane exhibited a permeation rate of 587.19 / m ² / day and a removal rate of 83% for lysine. The enantioselectivity for d-lysine was 90%.

Example 6

The enantioselective composite membrane prepared according to Example 1 was tested under standard conditions using a 0.1 wt% aqueous solution of racemic lysine as the feed at a flow rate of 500 ml / min at 552 KPa. The membrane exhibited a permeation rate of 293.54 / m ² / day and a removal rate of 46% for lysine, and the enantioselectivity for d-lysine was 60%.

Example 7

The enantioselective composite membrane prepared according to Example 1 was tested under standard conditions using a 0.05 wt% aqueous solution of racemic alanine as the feed at a flow rate of 500 ml / min at 552 KPa. The membrane exhibited a volumetric flux of 342.30 l / m ² / day and a lysine removal rate of 72%. The enantioselectivity for d-alanine was 56%.

Key Advantages of the Invention

1) The enantioselective polymer membranes described in the prior art are asymmetric and dense membranes made from chiral polymers such as polysaccharides and derivatives, poly-alpha-amino acids, polyacetylene derivatives and the like. Most membranes are prone to damage, have poor mechanical properties and are therefore difficult to handle membranes, so their use is limited only to the separation of the dialysis mode. In separation of the dialysis mode, the driving force is solute concentration gradient only through the membrane, and this membrane exhibits very low transmittance. Membranes with excellent mechanical properties initially exhibit enantioselectivity, but their selectivity decreases rapidly over time due to saturation of the recognition site.

2) The composite membrane of the present invention eliminates the drawbacks of the membrane described in the prior art as described above.

3) The composite membranes of the present invention can be used to isolate enantiomers on a commercial scale.

4) The composite membrane of the present invention exhibits a permeation flux of 6 to 24 gallons / ft ² / day, depending on the membrane penetration pressure.

5) The composite membrane of the present invention can be used in a pressure-driven separation method at a pressure varying from 345 to 862 KPa. The higher the membrane throughput pressure, the higher the flux and, consequently, the higher the productivity.

6) The composite membrane of the present invention is stable and mechanically excellent, so that it can be handled and switched to a modular type.

7) The enantiomer separation methods described in the previous paragraphs are often batch processes, even in successive cases, and are not suitable for large-scale sequential separation. Using the inventive membranes, the enantiomeric separation process can be a continuous process and can be adapted for large scale continuous separation.

8) The enantiomeric separation process of the present invention exhibits a reasonable period of separation and a high transport rate, enabling the separation of large amino acids from aqueous solutions and mixtures of amino acids.

Claims (11)

A process for preparing an enantioselective composite membrane useful for isolating an enantiomer from an enantiomeric mixture to obtain an optically pure isomer,
(a) providing an ultrafiltration (UF) membrane produced by a wet phase inversion method;
(b) filtering the ultrafiltration membrane obtained from step (a) with 1 to 2% by weight aqueous solution of a mixture of amino acids or amino acids, polyfunctional amines and acid acceptors for 1 to 5 minutes, maintaining the pH between 10 and 13 Dip coating with a mixture comprising;
(c) withdrawing the coated UF membrane from the mixture obtained from step (b) and draining the extra solution from the UF membrane for 5 to 30 minutes;
(d) immersing the coated membrane obtained from step (c) in a 0.1 to 1 wt% solution of triacyl halide in hexane for 1 to 5 minutes and evacuating the excess solution for 1 to 5 minutes;
(e) drying the membrane obtained in step (d) for 1 to 4 hours;
(f) heating the membrane obtained in step (e) at a temperature of 70 to 100 DEG C for 1 to 15 minutes, followed by cooling and air drying for 1 to 2 hours;
(g) immersing the membrane obtained in step (f) in deionized water for up to 24 hours to obtain an enantioselective composite membrane comprising an enantioselective layer on the ultrafiltration membrane and testing it for the separation of the amino acid from the aqueous amino acid solution
≪ / RTI > The method according to claim 1,
Wherein the thickness of the mirror selective layer of the composite film is in the range of 400 to 1600 angstroms. The method according to claim 1,
Wherein the amino acid used is selected from the group consisting of two or more primary amino groups. The method according to claim 1,
Wherein the enantioselective layer of the composite membrane comprises a crosslinked polyamide polymer having at least one chiral carbon atom. The method according to claim 1,
Wherein the multifunctional amine used in step (b) is selected from mephenylenediamine and piperidine, and wherein the acid acceptor used is selected from triethylamine and NaOH. The method according to claim 1,
Wherein the triacyl halide used in step (d) is trimesoyl chloride. The method according to claim 1,
Wherein the ultrafiltration membrane used for producing the composite membrane is selected from the group consisting of polysulfone and polyvinylidene fluoride having a thickness in the range of 20 to 60 占 퐉. The method according to claim 1,
Wherein the ultrafiltration membrane used for producing the composite membrane is selected from the group consisting of polyethersulfone and polyvinylidene fluoride having a thickness in the range of 20 to 60 占 퐉. The method according to claim 1,
Wherein the enantioselective composite membrane separates 50-70% arginine and 80-90% lysine from the aqueous solution. A method for enantioselective separation of a racemic mixture of amino acids using an enantioselective composite membrane obtained by the method of claim 1,
Carried out in a reverse osmosis membrane testing unit under a trans membrane pressure in the range of 345 to 862 KPa using an aqueous solution and / or buffer of amino acids in the range of 0.1 to 1% by weight as a feed at a flow rate in the range of 300 to 800 ml / Lt; / RTI > 11. The method of claim 10,
The concentration of amino acid in the permeate was measured by a UV-Vis spectrophotometer,
Wherein the ratio of the d and l-enantiomers in the permeate is measured on HPLC equipped with a PDA detector, using a chiral column.

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