A cyclodextrin / antibiotic composite membrane for tryptophan chiral separation and preparation method thereof

Abstract

The present invention discloses a cyclodextrin / antibiotic composite membrane for chiral separation of tryptophan and a preparation method thereof. The present invention uses cyclodextrin and aminoglycoside antibiotics as aqueous phase monomers, and deposits them on the surface of a porous support membrane through host-guest supramolecular action in the aqueous phase to construct a separation membrane with a chiral recognition nanochannel structure, and then enhances the stability of the nanochannel structure in the membrane through chemical cross-linking; and then enhances the function by surface grafting aminoglycoside antibiotics to prepare a high-performance chiral separation membrane. The chiral separation membrane has a permeation flux of 2.0*10 ‑3 ~3.5*10 ‑3 mol m ‑2 h ‑1 The chiral separation ee value of the mixed solution of tryptophan enantiomers can reach more than 60%. The present invention combines the advantages of multiple identification functional materials, the membrane preparation method is simple and controllable, easy to operate, and has low cost. The prepared membrane has good hydrophilicity, antibacterial properties and chiral separation stability, and its application in the separation of chiral amino acids has good application prospects.

Description

Technical Field

[0001] The invention belongs to the field of membrane separation, and in particular relates to a cyclodextrin / antibiotic composite membrane for tryptophan chiral separation and a preparation method thereof. Background Art

[0002] Chirality is a basic property of nature. Chiral molecules have the same chemical structure and very similar physical properties. Chiral drug molecules are isomers in spatial arrangement and are mirror images of each other. Drug molecules with different chiral structures have different physiological effects. One isomer molecule has a positive therapeutic effect, while the other has lower pharmacological activity or toxic side effects. Therefore, the identification and separation of chiral drug molecules is of great significance to the development of the life and health industry (Coordin. Chem. Rev., 2020, 425: 213481). Amino acids, as essential physiological components of the human body, mostly have chiral characteristics. Among them, D-type amino acids need to be converted into L-type amino acids in the human body before they can be absorbed and utilized. Once D-type amino acids exceed the human body's conversion limit, they will cause amino acid poisoning. Therefore, after synthesizing amino acids, they must be subjected to chiral separation treatment (J. Am. Chem. Soc., 2019, 141 (51): 20187-20197.). Traditional methods for splitting chiral drug molecules include chemical splitting, chromatographic splitting, enzymatic splitting, crystallization splitting, etc., but they usually have problems such as complex processes, low separation efficiency, and high costs. Membrane separation has the advantages of low energy consumption, high separation efficiency, and easy large-scale continuous production for splitting chiral drug molecules, which can greatly improve production efficiency. Therefore, the development of high-performance chiral separation membranes that can be used for the separation of amino acid enantiomers has important scientific significance and practical application prospects.

[0003] At present, the separation membranes used for chiral drug separation are mainly polymer membranes, usually with cellulose, sodium alginate, chitosan, etc. as membrane materials. The above polymers have the advantages of good film-forming properties and diverse membrane preparation methods, but the resulting membrane structure is relatively dense, and the separation efficiency and permeation flux need to be further improved (Coordin. Chem. Rev., 2022, 425: 213481). With the rapid development of nanomaterials, researchers have introduced porous nanomaterials into polymer membranes to improve the efficiency of membrane transfer to substances, but the generation of defective structures usually reduces the separation efficiency of chiral molecules. Therefore, it is urgent to develop new chiral recognition functional membrane materials and construct high-performance chiral separation membranes through simple and controllable preparation methods.

[0004] Cyclodextrin, as a non-toxic material with low preparation cost and unique cavity structure, has gradually been used in the preparation of separation membranes. Studies have found that the hydrophobic cavity diameter of cyclodextrin is 0.57 to 0.95 angstroms, which allows water to pass through, and is rich in a large number of chiral recognition sites, which can effectively separate chiral amino acid molecules (J. Mater. Chem. A, 2019, 7: 2055; Polymers 2019, 11: 1737). Aminoglycoside antibiotics have multiple chiral centers and multiple hydroxyl and amino functional groups, and have good film-forming properties. Introducing them into the interior and surface of the membrane as functional materials can further improve the chiral separation efficiency of the membrane. Summary of the invention

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a cyclodextrin / antibiotic composite membrane for tryptophan chiral separation and a preparation method. The present invention uses cyclodextrin and aminoglycoside antibiotics as aqueous phase monomers, and deposits them on the surface of a porous support membrane through host-guest supramolecular action in the aqueous phase to construct a separation membrane with a chiral recognition nanochannel structure, and then enhances the stability of the nanochannel structure in the membrane through chemical cross-linking; further, the surface is grafted with aminoglycoside antibiotics for functional enhancement to prepare a high-performance chiral separation membrane. Cyclodextrin has a unique hydrophobic chiral molecule recognition cavity structure, and aminoglycoside antibiotics are rich in amino groups and a large number of chiral active centers. It has a large number of six-membered ring structures that will play an important role in the amino acid separation process. The present invention combines the advantages of a variety of recognition functional materials, the membrane preparation method is simple and controllable, easy to operate, and has a low cost. The prepared membrane has good hydrophilicity, antibacterial properties and chiral separation stability, and its application in the separation of chiral amino acids has good application prospects.

[0006] The technical solution adopted by the present invention is as follows:

[0007] A method for preparing a cyclodextrin / antibiotic composite membrane for tryptophan chiral separation comprises the following steps:

[0008] 1) dissolving 0.1-0.5 parts by weight of cyclodextrin solid powder and 0.1-0.4 parts by weight of aminoglycoside antibiotics in 100 parts by weight of alkaline aqueous solution to obtain an aqueous solution, wherein the cyclodextrin and the aminoglycoside antibiotics in the aqueous solution form a host-guest complex through supramolecular action; then, impregnating the aqueous solution on the surface of a porous support membrane for molecular self-assembly surface deposition, and then impregnating with an organic cross-linking solution with a mass percentage concentration of 0.1-0.5wt% to obtain a cyclodextrin / antibiotic primary ecological composite membrane;

[0009] 2) immersing the cyclodextrin / antibiotic primary composite membrane in a 0.1-0.5wt% aminoglycoside antibiotic solution to carry out a surface grafting reaction, and finally subjecting the membrane to a thermal curing treatment and deionized water washing to form a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function;

[0010] The cyclodextrin described in step 1) is one or more of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and amphoteric cyclodextrin, mixed in any proportion; the aminoglycoside antibiotics described in step 1) and step 2) are one or more of tobramycin, gentamicin, kanamycin, streptomycin, and amikacin, mixed in any proportion; the porous support membrane described in step 1) is a polysulfone ultrafiltration membrane, a polyethersulfone ultrafiltration membrane, a polyacrylonitrile ultrafiltration membrane, and a polyvinylidene fluoride ultrafiltration membrane; the organic crosslinking agent in the organic crosslinking solution described in step 1) is one or more of isophthaloyl chloride, trimesoyl chloride, biphenyltetracarboxylic chloride, phthaloyl chloride, and trimesaldehyde, mixed in any proportion.

[0011] Among them, amphoteric cyclodextrin refers to cyclodextrin containing both anionic and cationic functional groups, and can be prepared by the following method:

[0012] 1.0-7.0 parts by weight of α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin, 2.5-12 parts by weight of zwitterionic amine monomer and 0.3-1.5 parts by weight of epoxy crosslinking agent are dissolved in 100 parts by weight of alkaline aqueous solution, reacted at 50-70°C for 1-4 hours, and after the reaction, the product is purified by dissolution and precipitation, and then heated and dried to obtain amphoteric cyclodextrin solid powder. The zwitterionic amine monomer is N-aminoethylpiperazine propane-1-sulfonic acid inner salt, 2,6-diaminopyridine propane-1-sulfonic acid inner salt, 2,6-diaminopyridine propane-1-carboxylic acid inner salt, 1,2-bis[N-methyl-N-(3-sulfopropyl)-alkylammonium]ethane, butanediol disuccinic acid dichlorohydroxypropyl quaternary ammonium diester sodium sulfonate, etc. Epoxy crosslinking agents include epichlorohydrin, di(2-epoxypropyl) ether, ethylene glycol diglycidyl ether, trimethylolpropane triglycidyl ether, and the like.

[0013] Preferably, the alkaline aqueous solution described in step 1) is a sodium hydroxide or potassium hydroxide aqueous solution with a mass percentage concentration of 0.01 to 1.0 wt%; preferably, the molecular self-assembly surface deposition condition described in step 1) is immersion deposition at 15 to 25°C for 2 to 10 minutes; preferably, the solvent of the organic cross-linking solution described in step 1) is n-hexane, heptane, cyclohexane or toluene; preferably, the organic solution immersion treatment condition described in step 1) is immersion at 15 to 25°C for 1 to 5 minutes; preferably, the surface grafting reaction condition described in step 2) is reaction at 15 to 25°C for 1 to 10 minutes; preferably, the thermal curing treatment condition described in step 2) is drying treatment at 20 to 60°C for 20 to 180 minutes.

[0014] A cyclodextrin / antibiotic composite membrane for tryptophan chiral separation prepared by the preparation method can be used in the field of separation of chiral amino acids.

[0015] The cyclodextrin / antibiotic composite membrane for chiral separation of tryptophan of the present invention uses cyclodextrin and aminoglycoside antibiotics as aqueous phase monomers, which are deposited on the surface of a porous support membrane through host-guest supramolecular action in the aqueous phase to construct a separation membrane with a chiral recognition nanochannel structure, and then the stability of the nanochannel structure in the membrane is enhanced by chemical cross-linking; further, aminoglycoside antibiotics are grafted on the surface for functional enhancement to prepare a high-performance chiral separation membrane. The chiral separation membrane has a permeation flux of 2.0*10 -3 ~3.5*10 -3 mol m -2 h -1 The chiral separation ee value of the mixed solution of tryptophan enantiomers can reach more than 60%. The present invention combines the advantages of multiple identification functional materials, the membrane preparation method is simple and controllable, easy to operate, and has low cost. The prepared membrane has good hydrophilicity, antibacterial properties and chiral separation stability, and its application in the separation of chiral amino acids has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a surface morphology of a cyclodextrin / antibiotic composite membrane for chiral separation of tryptophan according to Example 3 of the present invention. DETAILED DESCRIPTION

[0017] A method for preparing a cyclodextrin / antibiotic composite membrane for tryptophan chiral separation comprises the following steps:

[0018] 1) dissolving 0.1-0.5 parts by weight of cyclodextrin solid powder and 0.1-0.4 parts by weight of aminoglycoside antibiotics in 100 parts by weight of alkaline aqueous solution to obtain an aqueous solution, wherein the cyclodextrin and the aminoglycoside antibiotics in the aqueous solution form a host-guest complex through supramolecular action; then, impregnating the aqueous solution on the surface of a porous support membrane for molecular self-assembly surface deposition, and then impregnating with an organic cross-linking solution with a mass percentage concentration of 0.1-0.5wt% to obtain a cyclodextrin / antibiotic primary ecological composite membrane;

[0019] 2) immersing the cyclodextrin / antibiotic primary composite membrane in a 0.1-0.5wt% aminoglycoside antibiotic solution to carry out a surface grafting reaction, and finally subjecting the membrane to a thermal curing treatment and deionized water washing to form a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function;

[0020] The cyclodextrin described in step 1) is composed of one or more of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and amphoteric cyclodextrin mixed in any proportion; the aminoglycoside antibiotics described in step 1) and step 2) are composed of one or more of tobramycin, gentamicin, kanamycin, streptomycin, and amikacin mixed in any proportion; the porous support membrane described in step 1) is a polysulfone ultrafiltration membrane, a polyethersulfone ultrafiltration membrane, a polyacrylonitrile ultrafiltration membrane, and a polyvinylidene fluoride ultrafiltration membrane; the organic crosslinking agent described in step 1) is composed of one or more of isophthaloyl chloride, trimesoyl chloride, biphenyl tetracarboxylic chloride, phthaloyl chloride, and trimesaldehyde mixed in any proportion;

[0021] The alkaline aqueous solution described in step 1) is a sodium hydroxide or potassium hydroxide aqueous solution with a mass percentage concentration of 0.01 to 1.0 wt%; the molecular self-assembly surface deposition condition described in step 1) is immersion deposition at 15 to 25° C. for 2 to 10 minutes; the solvent of the organic cross-linking solution described in step 1) is n-hexane, heptane, cyclohexane or toluene; the organic solution immersion treatment condition described in step 1) is immersion at 15 to 25° C. for 1 to 5 minutes; the surface grafting reaction condition described in step 2) is reaction at 15 to 25° C. for 1 to 10 minutes; the thermal curing treatment condition described in step 2) is drying treatment at 20 to 60° C. for 20 to 180 minutes.

[0022] Examples of the present invention are given below, but the present invention is not limited to the examples.

[0023] In the following examples, the separation performance test method of the cyclodextrin / antibiotic composite membrane for tryptophan chiral separation is as follows: the membrane is placed in a pressure-driven membrane test device, and the membrane is pre-pressed at an operating pressure of 0.1 MPa for at least 0.5 h before the test, and then the solute permeation flux (J) and enantiomeric excess percentage (ee%) of the membrane are measured under the test conditions of 25° C. and 0.1 MPa, and the calculation formula is: Where V is the volume of the liquid permeating the membrane (L), A is the effective area of ​​the membrane, which is 19.6 cm 2 , Δt is the time of membrane testing (h); ΔC is the concentration change in the corresponding aqueous solution when the time increment is Δt, A D , A L It indicates the liquid chromatography peak area of ​​different chiral tryptophans. The tryptophan concentration is tested by liquid chromatography, and the tryptophan solution concentration is obtained by liquid chromatography test.

[0024] Embodiment 1:

[0025] 0.1g of β-cyclodextrin and 0.1g of tobramycin were dissolved in 100g of 0.01wt% sodium hydroxide aqueous solution, and β-cyclodextrin and tobramycin formed a host-guest complex through supramolecular action; then the aqueous phase solution was immersed on the surface of a polysulfone ultrafiltration membrane at 15°C for 2 minutes to perform molecular self-assembly surface deposition; then, 0.1wt% of trimesoyl chloride n-hexane solution was immersed at 15°C for 1 minute to obtain a cyclodextrin / antibiotic nascent composite membrane; then, the cyclodextrin / antibiotic nascent composite membrane was immersed in a 0.1wt% tobramycin solution, and a surface grafting reaction was performed at 15°C for 1 minute, and finally, a curing treatment was performed at 20°C for 180 minutes, and after washing with deionized water, a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function was formed.

[0026] The cyclodextrin / antibiotic composite membrane used for chiral separation of tryptophan has the following filtration separation effects for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure: the D-tryptophan permeation flux is 3.2*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 61.5%.

[0027] Embodiment 2:

[0028] 0.5g of β-cyclodextrin and 0.4g of tobramycin were dissolved in 100g of 1wt% sodium hydroxide aqueous solution, and β-cyclodextrin and tobramycin formed a host-guest complex through supramolecular action; then the aqueous phase solution was immersed on the surface of a polysulfone ultrafiltration membrane at 25°C for 10 minutes to perform molecular self-assembly surface deposition; then, 0.5wt% of trimesoyl chloride n-hexane solution was immersed at 25°C for 5 minutes to obtain a cyclodextrin / antibiotic nascent composite membrane; then, the cyclodextrin / antibiotic nascent composite membrane was immersed in a 0.5wt% tobramycin solution, and a surface grafting reaction was performed at 25°C for 10 minutes. Finally, the membrane was cured at 40°C for 20 minutes, and washed with deionized water to form a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function.

[0029] The cyclodextrin / antibiotic composite membrane used for chiral separation of tryptophan has the following filtration separation effects for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure: the D-tryptophan permeation flux is 2.4*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 63.4%.

[0030] Embodiment 3:

[0031] 0.3g of β-cyclodextrin and 0.25g of tobramycin were dissolved in 100g of 0.2wt% sodium hydroxide aqueous solution, and β-cyclodextrin and tobramycin formed a host-guest complex through supramolecular action; then the aqueous phase solution was immersed on the surface of a polysulfone ultrafiltration membrane at 20°C for 5 minutes to perform molecular self-assembly surface deposition; then, 0.2wt% of trimesoyl chloride n-hexane solution was immersed at 20°C for 2 minutes to obtain a cyclodextrin / antibiotic nascent composite membrane; then, the cyclodextrin / antibiotic nascent composite membrane was immersed in a 0.25wt% tobramycin solution, and a surface grafting reaction was performed at 20°C for 2 minutes, and finally, it was cured at 30°C for 60 minutes, and after washing with deionized water, a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function was formed.

[0032] The cyclodextrin / antibiotic composite membrane used for chiral separation of tryptophan has the following filtration separation effects for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure: the D-tryptophan permeation flux is 2.8*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 69.5%.

[0033] Comparative Example 1

[0034] Referring to the steps of Example 3, 0.3 g of β-cyclodextrin and 0.25 g of tobramycin were dissolved in 100 g of 0.2 wt % sodium hydroxide aqueous solution, and β-cyclodextrin and tobramycin formed a host-guest complex through supramolecular action; then the aqueous phase solution was immersed on the surface of a polysulfone ultrafiltration membrane at 20° C. for 5 minutes to perform molecular self-assembly surface deposition; and then immersed in 0.2 wt % trimesoyl chloride n-hexane solution at 20° C. for 2 minutes to obtain a cyclodextrin / antibiotic primary ecological composite membrane.

[0035] Comparative Example 2

[0036] Referring to the steps of Example 3, 0.3 g of β-cyclodextrin was dissolved in 100 g of a 0.2 wt % sodium hydroxide aqueous solution; the aqueous phase solution was then immersed on the surface of a polysulfone ultrafiltration membrane at 20° C. for 5 minutes to perform molecular self-assembly surface deposition; and then immersed in a 0.2 wt % trimesoyl chloride n-hexane solution at 20° C. for 2 minutes to obtain a cyclodextrin separation membrane.

[0037] Comparative Example 3

[0038] Referring to the steps of Example 3, 0.25 g of tobramycin was dissolved in 100 g of a 0.2 wt % sodium hydroxide aqueous solution; the aqueous phase solution was then immersed on the surface of a polysulfone ultrafiltration membrane at 20° C. for 5 minutes to perform molecular self-assembly surface deposition; and then immersed in a 0.2 wt % trimesoyl chloride n-hexane solution at 20° C. for 2 minutes to obtain an antibiotic separation membrane.

[0039] Table 1 Comparison of performance of different types of chiral separation membranes prepared in Example 3 and Comparative Examples 1-3

[0040]

[0041] The results in Table 1 show that since cyclodextrin / antibiotics all have tryptophan chiral recognition sites, chiral separation membranes can be prepared by the four methods, but their tryptophan separation capabilities and D-tryptophan permeation fluxes are quite different, which is caused by the different chemical compositions and microstructures of the obtained membranes.

[0042] In Comparative Example 1, the membrane surface was not modified with tobramycin, so the number of chiral recognition sites on the membrane surface was insufficient, and the chiral separation effect was reduced. In Comparative Example 2, only cyclodextrin was used as the aqueous phase monomer to prepare the chiral separation membrane, and the membrane had a channel structure, but lacked chiral recognition sites, so the membrane flux increased, but the chiral recognition ability was greatly reduced; in Comparative Example 3, only tobramycin was used as the aqueous phase monomer to prepare the chiral separation membrane, and the density of the membrane was improved. Although it had chiral separation performance, the permeation flux was low.

[0043] In Example 3, cyclodextrin and aminoglycoside antibiotics were used as aqueous phase monomers and deposited on the surface of a porous support membrane through host-guest supramolecular interaction in the aqueous phase to construct a separation membrane with a chiral recognition nanochannel structure. Furthermore, aminoglycoside antibiotics were grafted onto the surface to enhance the function and prepare a high-performance chiral separation membrane, such as Figure 1 As shown. Cyclodextrin has a unique hydrophobic chiral molecule recognition cavity structure, and aminoglycoside antibiotics are rich in amino groups and a large number of chiral active centers. They have a large number of six-membered ring structures that will play an important role in the amino acid splitting process. The present invention combines the advantages of multiple recognition functional materials, and the membrane preparation method is simple and controllable, easy to operate, and has low cost. The prepared membrane has good hydrophilicity, antibacterial properties and chiral separation stability, and has good application prospects.

[0044] Embodiment 4:

[0045] 0.2g of α-cyclodextrin and 0.3g of kanamycin are dissolved in 100g of 0.05wt% potassium hydroxide aqueous solution, and α-cyclodextrin and kanamycin form a host-guest complex through supramolecular action; then the aqueous phase solution is immersed on the surface of a polysulfone ultrafiltration membrane at 25°C for 8 minutes to perform molecular self-assembly surface deposition; then, it is immersed in 0.15wt% of trimesoyl chloride n-hexane solution at 25°C for 3 minutes to obtain a cyclodextrin / antibiotic nascent composite membrane; then, the cyclodextrin / antibiotic nascent composite membrane is immersed in 0.2wt% of kanamycin solution, and a surface grafting reaction is performed at 25°C for 5 minutes. Finally, it is cured at 25°C for 70 minutes, and after washing with deionized water, a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function is formed.

[0046] The cyclodextrin / antibiotic composite membrane used for chiral separation of tryptophan has the following filtration separation effects for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure: the D-tryptophan permeation flux is 2.4*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 68.2%.

[0047] Embodiment 5:

[0048] 0.3g of γ-cyclodextrin and 0.4g of gentamicin are dissolved in 100g of 0.1wt% sodium hydroxide aqueous solution, and γ-cyclodextrin and gentamicin form a host-guest complex through supramolecular action; then the aqueous phase solution is immersed on the surface of a polyvinylidene fluoride ultrafiltration membrane at 20°C for 10 minutes to perform molecular self-assembly surface deposition; then, it is immersed in a 0.25wt% isophthaloyl chloride cyclohexane solution at 20°C for 5 minutes to obtain a cyclodextrin / antibiotic nascent composite membrane; then, the cyclodextrin / antibiotic nascent composite membrane is immersed in a 0.3wt% gentamicin solution, and a surface grafting reaction is performed at 20°C for 10 minutes. Finally, it is cured at 40°C for 60 minutes, and after washing with deionized water, a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function is formed.

[0049] The cyclodextrin / antibiotic composite membrane used for chiral separation of tryptophan has the following filtration separation effects for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure: the D-tryptophan permeation flux is 2.5*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 61.8%.

[0050] Embodiment 6:

[0051] 0.4g of γ-cyclodextrin and 0.3g of streptomycin are dissolved in 100g of 0.3wt% potassium hydroxide aqueous solution, and γ-cyclodextrin and streptomycin form a host-guest complex through supramolecular action; then the aqueous phase solution is immersed on the surface of a polysulfone ultrafiltration membrane at 25°C for 5 minutes to perform molecular self-assembly surface deposition; then, 0.3wt% of biphenyltetracarbonyl chloride heptane solution is immersed at 25°C for 3 minutes to obtain a cyclodextrin / antibiotic primary ecological composite membrane; then, the cyclodextrin / antibiotic primary ecological composite membrane is immersed in a 0.5wt% streptomycin solution, and a surface grafting reaction is performed at 25°C for 10 minutes. Finally, the membrane is cured at 60°C for 30 minutes, and washed with deionized water to form a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function.

[0052] The cyclodextrin / antibiotic composite membrane used for chiral separation of tryptophan has the following filtration separation effects for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure: the D-tryptophan permeation flux is 3.1*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 60.2%.

[0053] Embodiment 7:

[0054] 0.25g of β-cyclodextrin and 0.25g of akamycin are dissolved in 100g of 0.5wt% sodium hydroxide aqueous solution, and β-cyclodextrin and akamycin form a host-guest complex through supramolecular action; then the aqueous phase solution is immersed on the surface of a polyacrylonitrile ultrafiltration membrane at 20°C for 8 minutes to perform molecular self-assembly surface deposition; then, 0.1wt% phthaloyl chloride cyclohexane solution is immersed at 20°C for 2 minutes to obtain a cyclodextrin / antibiotic nascent ecological composite membrane; then, the cyclodextrin / antibiotic nascent ecological composite membrane is immersed in a 0.25wt% akamycin solution, and a surface grafting reaction is performed at 20°C for 8 minutes, and finally, it is cured at 50°C for 50 minutes, and after washing with deionized water, a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function is formed.

[0055] The cyclodextrin / antibiotic composite membrane used for chiral separation of tryptophan has the following filtration separation effects for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure: the D-tryptophan permeation flux is 2.9*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 61.5%.

[0056] Embodiment 8:

[0057] 0.4g α-cyclodextrin and 0.3g kanamycin are dissolved in 100g 0.7wt% potassium hydroxide aqueous solution, and α-cyclodextrin and kanamycin form a host-guest complex through supramolecular action; then the aqueous phase solution is immersed on the surface of a polyethersulfone ultrafiltration membrane at 25°C for 10 minutes to perform molecular self-assembly surface deposition; then, it is immersed in 0.3wt% trimesaldehyde toluene solution at 25°C for 5 minutes to obtain a cyclodextrin / antibiotic primary ecology composite membrane; then, the cyclodextrin / antibiotic primary ecology composite membrane is immersed in 0.5wt% gentamicin solution, and a surface grafting reaction is performed at 25°C for 5 minutes, and finally, it is cured at 40°C for 100 minutes, and after washing with deionized water, a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function is formed.

[0058] The cyclodextrin / antibiotic composite membrane used for chiral separation of tryptophan has the following filtration separation effects for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure: the D-tryptophan permeation flux is 2.1*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 68.6%.

[0059] Embodiment 9:

[0060] 4.0 g of α-cyclodextrin, 10 g of N-aminoethylpiperazine propane-1-sulfonic acid inner salt and 0.9 g of epichlorohydrin were dissolved in 100 g of 0.05 wt% sodium hydroxide aqueous solution, and reacted at 60° C. for 2 hours. After the reaction, the product was dissolved in water and precipitated with methanol for purification three times, and then heated and dried at 40° C. for 12 hours to obtain amphoteric cyclodextrin.

[0061] 0.3g of amphoteric cyclodextrin and 0.25g of kanamycin are dissolved in 100g of 0.5wt% sodium hydroxide aqueous solution, and the amphoteric cyclodextrin and kanamycin form a host-guest complex through supramolecular action; then the above aqueous phase solution is immersed on the surface of a polysulfone ultrafiltration membrane at 20°C for 5 minutes to perform molecular self-assembly surface deposition; then it is immersed in 0.2wt% trimesoyl chloride n-hexane solution at 25°C for 2 minutes to obtain an amphoteric cyclodextrin / antibiotic nascent ecological composite membrane; then the above amphoteric cyclodextrin / antibiotic nascent ecological composite membrane is immersed in 0.3wt% tobramycin solution, and a surface grafting reaction is performed at 25°C for 2 minutes, and finally it is cured at 30°C for 60 minutes, and after washing with deionized water, an amphoteric cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function is formed.

[0062] The filtration separation effect of the amphiphilic cyclodextrin / antibiotic composite membrane for chiral separation of tryptophan for 0.1 mmol / L L, D-tryptophan solution at 25°C and 0.1 MPa pressure is as follows: the permeation flux of D-tryptophan is 2.6*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 69.6%.

[0063] Embodiment 10:

[0064] 7.0 g of β-cyclodextrin, 12 g of 2,6-diaminopyridinepropane-1-carboxylic acid inner salt and 1.2 g of di(2-epoxypropyl) ether were dissolved in 100 g of 1 wt% potassium hydroxide aqueous solution, and reacted at 55° C. for 4 hours. After the reaction, the product was purified 5 times by dissolving in water and precipitating with methanol, and then heated and dried at 60° C. for 10 hours to obtain amphoteric cyclodextrin.

[0065] 0.5g of amphoteric cyclodextrin and 0.4g of gentamicin are dissolved in 100g of 0.05wt% sodium hydroxide aqueous solution, and the amphoteric cyclodextrin and gentamicin form a host-guest complex through supramolecular action; then the aqueous phase solution is immersed on the surface of a polyvinylidene fluoride ultrafiltration membrane at 20°C for 10 minutes to perform molecular self-assembly surface deposition; then, it is immersed in 0.25wt% trimesoyl chloride n-hexane solution at 25°C for 5 minutes to obtain an amphoteric cyclodextrin / antibiotic primary ecological composite membrane; then, the amphoteric cyclodextrin / antibiotic primary ecological composite membrane is immersed in a 0.5wt% tobramycin solution, and a surface grafting reaction is performed at 25°C for 5 minutes. Finally, it is cured at 25°C for 120 minutes, and after washing with deionized water, an amphoteric cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function is formed.

[0066] The filtration separation effect of the amphiphilic cyclodextrin / antibiotic composite membrane for chiral separation of tryptophan at 25°C and 0.1 MPa pressure for 0.1 mmol / L L, D-tryptophan solution is: the D-tryptophan permeation flux is 2.1*10 -3 mol m -2 h -1 The ee value of L,D-tryptophan resolution is 62.4%.

Claims

1. A method for preparing a cyclodextrin / antibiotic composite membrane for chiral separation of tryptophan, characterized in that: The steps include: 1) dissolving 0.1-0.5 parts by weight of cyclodextrin solid powder and 0.1-0.4 parts by weight of aminoglycoside antibiotics in 100 parts by weight of alkaline aqueous solution to obtain an aqueous solution, wherein the cyclodextrin and the aminoglycoside antibiotics in the aqueous solution form a host-guest complex through supramolecular action; then, impregnating the aqueous solution on the surface of a porous support membrane for molecular self-assembly surface deposition, and then impregnating with an organic cross-linking solution with a mass percentage concentration of 0.1-0.5wt% to obtain a cyclodextrin / antibiotic primary ecological composite membrane; 2) immersing the cyclodextrin / antibiotic primary composite membrane in a 0.1-0.5wt% aminoglycoside antibiotic solution to carry out a surface grafting reaction, and finally subjecting the membrane to thermal curing and washing to form a cyclodextrin / antibiotic composite membrane with enhanced surface chiral molecule recognition function; Among them, the cyclodextrin is composed of one or more of α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and amphoteric cyclodextrin mixed in any proportion; the aminoglycoside antibiotics are composed of one or more of tobramycin, gentamicin, kanamycin, streptomycin, and amikacin mixed in any proportion; the porous support membrane is a polysulfone ultrafiltration membrane, a polyethersulfone ultrafiltration membrane, a polyacrylonitrile ultrafiltration membrane, and a polyvinylidene fluoride ultrafiltration membrane; the organic crosslinking agent in the organic crosslinking solution is composed of one or more of isophthaloyl chloride, trimesoyl chloride, biphenyltetracarboxylic chloride, phthaloyl chloride, and trimesaldehyde mixed in any proportion.

2. The preparation method according to claim 1, characterized in that The alkaline aqueous solution described in step 1) is a sodium hydroxide or potassium hydroxide aqueous solution with a mass percentage concentration of 0.01 to 1.0 wt%.

3. The preparation method according to claim 1, characterized in that: The conditions for the molecular self-assembly surface deposition in step 1) are immersion deposition at 15-25° C. for 2-10 minutes.

4. The preparation method according to claim 1, characterized in that: The solvent of the organic cross-linking solution in step 1) is n-hexane, heptane, cyclohexane or toluene.

5. The preparation method according to claim 1, characterized in that: The immersion treatment condition of the organic crosslinking solution in step 1) is immersion at 15 to 25° C. for 1 to 5 minutes.

6. The preparation method according to claim 1, characterized in that the surface grafting reaction in step 2) is carried out at 15-25°C for 1-10 minutes.

7. The preparation method according to claim 1, characterized in that the heat curing treatment in step 2) is carried out under the condition of drying at 20 to 60°C for 20 to 180 minutes.

8. A cyclodextrin / antibiotic composite membrane for chiral separation of tryptophan prepared by the preparation method according to any one of claims 1 to 7.

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