Preparation method of chiral polyester composite film based on spirodiphenol as well as product and application of chiral polyester composite film
The chiral polyester composite film based on spirocyclic diphenol was prepared through interface polymerization, and combined with the electronic control device, the problem of insufficient research on the complexity of existing chiral drug separation methods and the integration was solved, and high-efficiency and low-cost hand The effect of sexual separation has promoted its application in many fields.
Patent Information
- Application Number
- CN202411467493.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-21
- Publication Date
- 2024-12-20
AI Technical Summary
The existing chiral drug separation methods have complex operational steps, expensive equipment and difficult to achieve large-scale production. The integration of chiral separation membranes has not yet been studied in depth, which limits its use in pharmaceuticals, chemicals, food and environmental protection fields. Widely used.
The chiral polyester composite membrane based on spirocyclic diphenol was prepared by interfacial polymerization. The polyacrylonitrile ultrafiltration membrane was immersed and dried in the aqueous monomer solution of the active layer and the oil phase monomer solution, and combined with the general electronic control The device adjusts the separation parameters and builds a chiral membrane separation integrated system.
It realizes efficient chiral separation of chiral membranes continuously prepared on a large area, simplifies operation, reduces costs, improves the separation efficiency of enantiomer molecules, and is suitable for efficient separation of a variety of drugs.
Smart Images
Figure CN119158428A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of polyester composite films, and relates to a preparation method of a chiral polyester composite film based on spirocyclic diphenol, a product thereof and an application thereof. Background Art
[0002] Chirality is a common phenomenon, such as amino acids, sugars, and nucleic acids that make up life; most drugs used to treat diseases are chiral. Due to the high stereoselectivity of enzyme reactions and other biological processes, chiral drug enantiomers usually show different pharmacological activities, metabolic effects, metabolic rates, and toxicity during metabolism. In some cases, only one enantiomer of a chiral drug can exert the desired effect, while the other enantiomer has no effect or weaker effect, and may even produce side effects or toxicity. Therefore, large-scale production of single enantiomer compounds has important scientific significance and economic value.
[0003] The mainstream chiral separation methods currently include crystallization separation, kinetic separation, and chromatographic separation. Although these methods have shown potential application value and prospects in the separation of chiral drugs, there are still some drawbacks that need to be further overcome. For example, these methods have complex operating steps, expensive equipment, and difficulty in large-scale production. Membrane separation technology can well meet the needs of preparing pure enantiomers on a commercial scale due to its high efficiency, low energy consumption, simplicity, and continuous operation. Separation membranes usually rely on sieving and dissolution-diffusion to limit and transfer fluid substances to achieve separation purposes. Current research on chiral separation membranes mainly focuses on the design and synthesis of membrane materials, the regulation of structure and performance, and the balance between selectivity and permeability. However, despite significant progress in these basic research fields, research on the integration of chiral separation membranes and their further applications is still relatively rare. Integrated research involves the effective integration of chiral separation membranes with existing separation technologies or equipment to achieve higher operating efficiency and a wider range of applications. This includes modular design of membranes, their combination with other separation units, and how to efficiently and economically deploy and maintain them in actual industrial processes.
[0004] At present, the research and development of these integrated technologies is still in its infancy. Future research will need to explore in more depth how to transform chiral separation membrane technology from the laboratory into practical applications to achieve its wide application in the fields of pharmaceuticals, chemicals, food, and environmental protection. Summary of the invention
[0005] In view of this, one of the objects of the present invention is to provide a method for preparing a chiral polyester composite membrane based on spirodiphenol; a second object of the present invention is to provide a chiral polyester composite membrane based on spirodiphenol; a third object of the present invention is to provide an application of a chiral polyester composite membrane based on spirodiphenol in the chiral separation of racemates.
[0006] In order to achieve the above object, the present invention provides the following technical solutions:
[0007] 1. A method for preparing a chiral polyester composite film based on spirocyclic diphenol, the preparation method being as follows:
[0008] The polyacrylonitrile ultrafiltration membrane is immersed in the active layer aqueous phase monomer solution for 5 to 7 minutes, taken out, and the excess solution on the surface is removed and then immersed in the active layer oil phase monomer solution for 1 to 5 minutes. After the immersion is completed, the membrane is taken out and dried to obtain a chiral polyester composite membrane based on spirocyclic diphenol;
[0009] The active layer aqueous phase monomer in the active layer aqueous phase monomer solution is S-spirocyclic diphenol.
[0010] Preferably, the polyacrylonitrile ultrafiltration membrane is prepared according to the following method:
[0011] The polyacrylonitrile was used as a support layer material and soaked in deionized water for 4 hours. The polyacrylonitrile ultrafiltration membrane was obtained after being wiped dry with lens paper.
[0012] Preferably, the active layer aqueous monomer solution contains aqueous monomers at a concentration of 1 to 2 wt% and sodium hydroxide at a concentration of 0.2 to 0.8 wt%.
[0013] Preferably, the concentration of the oil phase monomer in the active layer oil phase monomer solution is 0.05-0.2 wt %.
[0014] Preferably, the active layer oil phase monomer in the active layer oil phase monomer solution is trimesoyl chloride.
[0015] Preferably, the solvent in the active layer oil phase monomer solution is n-hexane.
[0016] 2. The chiral polyester composite film based on spirocyclic diphenol is prepared according to the above preparation method.
[0017] 3. Application of the above-mentioned spirocyclic diphenol-based chiral polyester composite membrane in the chiral separation of racemates.
[0018] The beneficial effects of the present invention are as follows: the present invention discloses a method for preparing a chiral polyester composite membrane based on spirodiphenol, which mainly involves placing a polyacrylonitrile ultrafiltration membrane in an active layer aqueous phase monomer solution (the monomer is S-spirodiphenol) and an oil phase monomer solution in turn through an interfacial polymerization method, and drying to obtain a chiral polyester composite membrane based on spirodiphenol. The present invention prepares a chiral polyester composite membrane based on S-spirodiphenol through an interfacial polymerization method, and the method has the characteristics of large-area continuous preparation of chiral membranes; secondly, an electronic master control device is introduced to adjust various parameters in the separation process, and a chiral membrane separation integrated system is constructed; compared with the traditional system of connecting scattered parts, the chiral membrane separation integrated system is simpler and allows us to observe the operating status of the system more clearly so as to facilitate its regulation at any time. The membrane device has low cost, simple manufacture, and convenient operation, and can achieve efficient chiral separation of multiple enantiomeric molecules.
[0019] Other advantages, objectives and features of the present invention will be described in the following description to some extent, and to some extent, will be obvious to those skilled in the art based on the following examination and study, or can be taught from the practice of the present invention. The objectives and other advantages of the present invention can be realized and obtained through the following description. BRIEF DESCRIPTION OF THE DRAWINGS
[0020] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention will be described in detail below in conjunction with the accompanying drawings, wherein:
[0021] Figure 1 The results of separation of ibuprofen racemate using the chiral polyester composite membrane based on spirodiphenol in Example 2;
[0022] Figure 2 The results of separation of propranolol hydrochloride racemate using the chiral polyester composite membrane based on spirodiphenol in Example 3;
[0023] Figure 3 The results of separation of atenolol racemate using the chiral polyester composite membrane based on spirodiphenol in Example 4;
[0024] Figure 4 The results of the separation of ibuprofen racemate using the chiral polyester composite membrane based on spirodiphenol in Comparative Example 1 are as follows;
[0025] Figure 5 The results of the separation of the propranolol hydrochloride racemate using the chiral polyester composite membrane based on spirodiphenol in Comparative Example 2 are as follows;
[0026] Figure 6 The results of comparing the separation of atenolol racemate using the chiral polyester composite membrane based on spirodiphenol in Example 3. DETAILED DESCRIPTION
[0027] The following describes the embodiments of the present invention by specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that the illustrations provided in the following embodiments only illustrate the basic concept of the present invention in a schematic manner, and the following embodiments and features in the embodiments can be combined with each other without conflict.
[0028] The structures of the chiral polyester active layers involved in the following Examples 2 to 4 and Comparative Examples 1 to 3 are as follows:
[0029]
[0030] Example 1
[0031] Preparation of chiral polyester composite film based on spirocyclic diphenol, the specific method is as follows:
[0032] (1) Preparation of polyacrylonitrile ultrafiltration membrane: A polyacrylonitrile ultrafiltration membrane (size: 10×10 cm) was used as a support layer material and soaked in 20 mL of deionized water for 4 h. The polyacrylonitrile ultrafiltration membrane was obtained after being wiped dry with lens paper.
[0033] (2) Preparation of active layer aqueous monomer solution: 0.2 g of S-spirodiphenol as an active layer aqueous monomer and 0.12 g of sodium hydroxide were added to 20 mL of deionized water, and an active layer oil phase monomer solution with a concentration of 39.63 mM was obtained by ultrasonic treatment.
[0034] (3) Preparation of oil phase monomer solution: 0.01 g of trimesoyl chloride as an active layer oil phase monomer was added to 20 mL of n-hexane, and an active layer oil phase monomer solution with a concentration of 22.60 mM was obtained by ultrasonic treatment.
[0035] (4) The polyacrylonitrile ultrafiltration membrane in step (1) is immersed in the active layer aqueous phase monomer solution in step (2) for 6 minutes, taken out, and the excess solution on the surface is removed and then immersed in the active layer oil phase monomer solution in step (3) for 3 minutes. After the immersion is completed, the membrane is taken out and dried to obtain a chiral polyester composite membrane based on spirodiphenol.
[0036] Example 2
[0037] Preparation of chiral polyester composite film based on spirocyclic diphenol, the specific method is as follows:
[0038] (1) Preparation of polyacrylonitrile ultrafiltration membrane: A polyacrylonitrile ultrafiltration membrane (size: 10×10 cm) was used as a support layer material and soaked in 20 mL of deionized water for 4 h. The polyacrylonitrile ultrafiltration membrane was obtained after being wiped dry with lens paper.
[0039] (2) Preparation of active layer aqueous monomer solution: 0.4 g of S-spirodiphenol as an active layer aqueous monomer and 0.12 g of sodium hydroxide were added to 20 mL of deionized water, and an active layer oil phase monomer solution with a concentration of 79.26 mM was obtained by ultrasonic treatment.
[0040] (3) Preparation of oil phase monomer solution: 0.02 g of trimesoyl chloride as an active layer oil phase monomer was added into 20 mL of n-hexane, and an active layer oil phase monomer solution with a concentration of 45.20 mM was obtained by ultrasonic treatment.
[0041] (4) The polyacrylonitrile ultrafiltration membrane in step (1) is immersed in the active layer aqueous phase monomer solution in step (2) for 5 minutes, taken out, and after removing the excess solution on the surface, it is continuously immersed in the active layer oil phase monomer solution in step (3) for 1 minute. After the immersion is completed, the membrane is taken out and dried to obtain a chiral polyester composite membrane based on spirodiphenol.
[0042] Example 3
[0043] Preparation of chiral polyester composite film based on spirocyclic diphenol, the specific method is as follows:
[0044] (1) Preparation of polyacrylonitrile ultrafiltration membrane: A polyacrylonitrile ultrafiltration membrane (size: 10×10 cm) was used as a support layer material and soaked in 20 mL of deionized water for 4 h. The polyacrylonitrile ultrafiltration membrane was obtained after being wiped dry with lens paper.
[0045] (2) Preparation of active layer aqueous monomer solution: 0.6 g of S-spirocyclodiphenol as an active layer aqueous monomer and 0.12 g of sodium hydroxide were added to 20 mL of deionized water, and an active layer oil phase monomer solution with a concentration of 118.89 mM was obtained by ultrasonic treatment.
[0046] (3) Preparation of oil phase monomer solution: 0.04 g of trimesoyl chloride as an active layer oil phase monomer was added into 20 mL of n-hexane, and an active layer oil phase monomer solution with a concentration of 90.40 mM was obtained by ultrasonic treatment.
[0047] (4) The polyacrylonitrile ultrafiltration membrane in step (1) is immersed in the active layer aqueous phase monomer solution in step (2) for 7 minutes, taken out, and the excess solution on the surface is removed and then immersed in the active layer oil phase monomer solution in step (3) for 5 minutes. After the immersion is completed, the membrane is taken out and dried to obtain a chiral polyester composite membrane based on spirodiphenol.
[0048] Example 4
[0049] The chiral polyester composite membrane based on spirodiphenol prepared in Example 1 above was used for the separation of ibuprofen racemate, specifically:
[0050] Preparation of 2 mg / mL ibuprofen racemate (n S-布洛芬 :n R-布洛芬 =50:50) of ethanol feed liquid, the prepared chiral polyester composite membrane was fixed in the inner tube of the membrane assembly, the pump pressure and flow rate were regulated by the electronic master control device, the feed liquid was separated through the chiral polyester composite membrane based on spirodiphenol prepared in the above Example 1, the feed liquid was taken out for high performance liquid chromatography test, and most of the discharge liquid after passing through the membrane was R-ibuprofen, and the ee% value reached 95.4%. Figure 1 As shown, it indicates that the chiral polyester composite membrane achieves high retention of S-ibuprofen and exhibits a high chiral separation effect.
[0051] Example 5
[0052] The chiral polyester composite membrane based on spirodiphenol prepared in the above Example 1 is used for the separation of the propranolol hydrochloride racemate, specifically:
[0053] Preparation of 2 mg / mL propranolol hydrochloride racemate (n S-盐酸普萘洛尔 :n R-盐酸普萘洛尔 =50:50) of ethanol feed liquid, the prepared chiral polyester composite membrane was fixed in the inner tube of the membrane assembly, the pump pressure and flow rate were regulated by the electronic master control device, so that the feed liquid passed through the chiral polyester composite membrane based on spirodiphenol prepared in the above Example 1 for separation, and the feed liquid was taken out for high performance liquid chromatography test. Most of the discharge liquid after passing through the membrane was R-propranolol hydrochloride, and the ee% value reached 92.7%. Figure 2 As shown, it indicates that the chiral polyester composite membrane has a good retention effect on S-propranolol hydrochloride and exhibits good chiral separation performance.
[0054] Example 6
[0055] The chiral polyester composite membrane based on spirodiphenol prepared in Example 1 above was used for the separation of atenolol racemate, specifically:
[0056] Preparation of 2 mg / mL atenolol racemate (n S-阿替洛尔 :n R-阿替洛尔 =50:50) of ethanol feed liquid, the prepared chiral polyester composite membrane was fixed in the inner tube of the membrane assembly, the pump pressure and flow rate were regulated by the electronic master control device, the feed liquid was separated through the chiral polyester composite membrane based on spirodiphenol prepared in the above Example 1, the feed liquid was taken out for high performance liquid chromatography test, and most of the discharge liquid after passing through the membrane was R-atenolol, and the ee% value reached 83.2%. Figure 3As shown, it indicates that the chiral polyester composite membrane has a good retention effect on S-atenolol and exhibits good chiral separation performance.
[0057] Comparative Example 1
[0058] The polyacrylonitrile ultrafiltration membrane was used for the separation of ibuprofen racemate, as shown in the following method:
[0059] Preparation of 2 mg / mL ibuprofen racemate (n S-布洛芬 :n R-布洛芬 =50:50) ethanol feed liquid, fix the polyacrylonitrile ultrafiltration membrane in the inner tube of the membrane assembly, adjust the pump pressure and flow rate by the electronic master control device, make the feed liquid pass through the membrane for separation, take out the feed liquid for high performance liquid chromatography test, the ee% value is 0.2%, such as Figure 4 As shown, it is explained that the polyacrylonitrile ultrafiltration membrane has no separation effect on the ibuprofen racemate, and the separation effect in the embodiment is produced by the chiral polyester active layer.
[0060] Comparative Example 2
[0061] The polyacrylonitrile ultrafiltration membrane was used for the separation of the propranolol hydrochloride racemate, as shown in the following method:
[0062] Preparation of 2 mg / mL propranolol hydrochloride racemate (n S-盐酸普萘洛尔 :n R-盐酸普萘洛尔 =50:50) ethanol feed liquid, fix the polyacrylonitrile ultrafiltration membrane in the inner tube of the membrane assembly, adjust the pump pressure and flow rate by the electronic master control device, make the feed liquid pass through the membrane for separation, take out the feed liquid for high performance liquid chromatography test, the ee% value is 0.6%, such as Figure 5 As shown, it is explained that the polyacrylonitrile ultrafiltration membrane has no separation effect on the propranolol hydrochloride racemate, and the separation effect in the embodiment is produced by the chiral polyester active layer.
[0063] Comparative Example 3
[0064] The polyacrylonitrile ultrafiltration membrane was used for the separation of the atenolol racemate, as shown in the following method.
[0065] Preparation of 2 mg / mL atenolol racemate (n S-阿替洛尔 :n R-阿替洛尔 =50:50) ethanol feed liquid, fix the polyacrylonitrile ultrafiltration membrane in the inner tube of the membrane assembly, adjust the pump pressure and flow rate by the electronic master control device, make the feed liquid pass through the membrane for separation, take out the feed liquid for high performance liquid chromatography test, the ee% value is 0.2%, such as Figure 6 As shown, it is explained that the polyacrylonitrile ultrafiltration membrane has no separation effect on the atenolol racemate, and the separation effect in the embodiment is produced by the chiral polyester active layer.
[0066] from Figure 1 and Figure 4 , Figure 2 and Figure 5 , Figure 3 and Figure 6 It can be seen from the comparison that compared with the polyacrylonitrile ultrafiltration membrane, the chiral polyester composite membrane based on spirodiphenol prepared by the present invention is used for the separation of ibuprofen racemate, propranolol racemate and atenolol racemate, respectively, and has good chiral separation characteristics.
[0067] Similarly, the chiral polyester composite membranes based on spirodiphenol prepared in Examples 2 and 3 were also used for the separation of ibuprofen racemate, propranolol racemate and atenolol racemate according to the schemes of Examples 4 to 6. The results were basically the same as the separation effect of the chiral polyester composite membrane based on spirodiphenol prepared in Example 1, which shows that the chiral polyester composite membrane based on spirodiphenol prepared by the method of the present invention can indeed be used for the chiral separation of ibuprofen racemate, propranolol racemate and atenolol racemate.
[0068] In summary, the present invention discloses a method for preparing a chiral polyester composite membrane based on spirodiphenol, which mainly involves placing a polyacrylonitrile ultrafiltration membrane in an active layer aqueous phase monomer solution (monomer is S-spirodiphenol) and an oil phase monomer solution in turn through an interfacial polymerization method, and drying to obtain a chiral polyester composite membrane based on spirodiphenol. The present invention prepares a chiral polyester composite membrane based on S-spirodiphenol through an interfacial polymerization method, and the method has the characteristics of large-area continuous preparation of chiral membranes; secondly, an electronic master control device is introduced to adjust various parameters in the separation process, and a chiral membrane separation integrated system is constructed; compared with the traditional system of connecting scattered parts, the chiral membrane separation integrated system is simpler and allows us to observe the operating status of the system more clearly so as to facilitate its regulation at any time. The membrane device has low cost, simple manufacture, and convenient operation, and can achieve efficient chiral separation of multiple enantiomeric molecules.
[0069] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the purpose and scope of the technical solution, which should be included in the scope of the claims of the present invention.
Claims
1. A method for preparing a chiral polyester composite film based on spirocyclic diphenol, characterized in that: The preparation method is as follows: The polyacrylonitrile ultrafiltration membrane is immersed in the active layer aqueous phase monomer solution for 5 to 7 minutes, taken out, and the excess solution on the surface is removed and then immersed in the active layer oil phase monomer solution for 1 to 5 minutes. After the immersion is completed, the membrane is taken out and dried to obtain a chiral polyester composite membrane based on spirocyclic diphenol; The active layer aqueous phase monomer in the active layer aqueous phase monomer solution is S-spirocyclic diphenol.
2. The preparation method according to claim 1, characterized in that: The polyacrylonitrile ultrafiltration membrane is prepared according to the following method: The polyacrylonitrile is used as a support layer material and immersed in deionized water, and then wiped dry with lens cleaning paper to obtain a polyacrylonitrile ultrafiltration membrane.
3. The preparation method according to claim 1, characterized in that: The active layer aqueous phase monomer solution contains aqueous phase monomers with a concentration of 1-2 wt% and sodium hydroxide with a concentration of 0.2-0.8 wt%.
4. The preparation method according to claim 1, characterized in that: The concentration of the oil phase monomer in the active layer oil phase monomer solution is 0.05-0.2 wt %.
5. The preparation method according to claim 1, characterized in that: The active layer oil phase monomer in the active layer oil phase monomer solution is trimesoyl chloride.
6. The preparation method according to claim 1, characterized in that: The solvent in the active layer oil phase monomer solution is n-hexane.
7. A chiral polyester composite film based on spirocyclic diphenol prepared according to the preparation method according to any one of claims 1 to 6.
8. Use of the chiral polyester composite membrane based on spirocyclic diphenol as claimed in claim 7 in the chiral separation of racemates.