Composite nanofiltration membrane with surface-enhanced raman detection function and its application in drug separation and detection

Abstract

The application discloses a composite nanofiltration membrane with a surface-enhanced Raman detection function and a medicine separation and detection application thereof, and relates to the technical field of nanofiltration membranes. The method comprises the following steps: after a metal polyphenol network (MPN) layer is prepared on a base film, silver nanoparticles are in-situ grown on the MPN layer to obtain a composite nanofiltration membrane. The method is carried out in an aqueous phase, and thus, organic solvents are avoided, and the demand of green chemistry is met; the prepared composite nanofiltration membrane has excellent separation performance and permeation performance, and meanwhile, rapid in-situ detection can be realized, and whether medicines and harmful substances are effectively separated can be judged, and the composite nanofiltration membrane can be applied to the field of medicine separation based on nanofiltration technology.

Description

Technical Field

[0001] This invention relates to the field of membrane technology, specifically to a composite nanofiltration membrane with surface-enhanced Raman detection function and its application in drug separation and detection. Background Technology

[0002] Hypertension is one of the most common diseases, and its treatment is primarily medication. Irbesartan is the first-line drug for treating essential hypertension, but its manufacturing process generates harmful nitrosamines, such as N,nitrosodimethylamine and N,nitrosodiethylamine. Therefore, the current technology is insufficient in how to separate these harmful substances from the drug during the manufacturing process and simultaneously monitor the separation effect in situ.

[0003] Nanofiltration, a pressure-driven membrane separation process between ultrafiltration and reverse osmosis, is an important membrane separation technology. Compared with traditional separation technologies, it has broad application prospects in fields such as drug separation, wastewater treatment, and seawater desalination due to its advantages of low energy consumption, no secondary pollution, simple operation, and high separation efficiency. Nanofiltration membranes have pore sizes between 0.5-2 nm and carry surface charges, allowing for the separation of ions based on their size or charge. For example, CN111203107A discloses a polyphenol-iron nanofilm, its preparation method, and its application. The polyphenol-iron nanofilm is obtained by immersing a porous supported membrane in a polyphenol aqueous solution, adding an aqueous solution of ferrous salt, shaking and co-depositing, and continuing the reaction at 70°C. The membrane prepared by this method can not only sieve monovalent and polyvalent ions in aqueous solutions but also achieve efficient retention of dye molecules in organic solvents. However, the membrane prepared by this invention only achieves separation performance and cannot achieve surface-enhanced Raman detection.

[0004] Surface-enhanced Raman spectroscopy (SERS) enables in-situ detection and can reveal molecular structural information. A Raman substrate is constructed on a nanofiltration membrane, and Raman detection is performed on the separated nanofiltration membrane. The position of characteristic peaks indicates whether harmful substances have been removed. CN106731885A discloses a metal-organic framework-metal nanoparticle ion composite filter membrane, its preparation method, and its application. Prepared metal nanoparticles are assembled onto a membrane substrate via chemical bonds, and a metal-organic framework is grown in situ on the surface of the metal nanoparticles to obtain the metal-organic framework-metal nanoparticle ion composite filter membrane. The composite filter membrane prepared by this method adsorbs organic pollutants using an injection filtration method, and finally, surface-enhanced Raman detection is performed directly. This invention utilizes a metal-organic framework to achieve the adsorption of organic pollutants, followed by surface-enhanced Raman detection using metal nanoparticles. Although this method can directly perform surface-enhanced Raman detection, the membrane product requires the use of complex metal-organic framework materials, limiting its industrial application.

[0005] Compared to the adsorption effect of membranes, membrane filtration technology does not require the addition of chemical agents, thus avoiding secondary pollution, making it more environmentally friendly, and also easier to clean and regenerate.

[0006] Based on nanofiltration separation technology and surface-enhanced Raman detection method, this invention prepares a composite nanofiltration membrane with surface-enhanced Raman detection function, realizing the integration of drug separation and detection. Summary of the Invention

[0007] [Technical Issues]

[0008] To address the aforementioned issues, this invention provides a composite nanofiltration membrane with surface-enhanced Raman detection functionality. Furthermore, the composite nanofiltration membrane utilizes a simple MPN membrane, eliminating the need to construct a complex organic framework structure.

[0009] [Technical Solution]

[0010] The purpose of this invention is to provide a method for preparing a composite nanofiltration membrane with surface-enhanced Raman detection function, comprising the following steps:

[0011] (1) The porous support membrane is first soaked in a polyphenol solution for a period of time, then ferrous salt aqueous solution is added and the membrane is shaken and co-deposited for a period of time. Finally, it is heat-treated to further react and obtain a metal polyphenol network layer (MPN layer).

[0012] (2) The film with the MPN layer is immersed in silver nitrate solution A for a certain period of time to obtain the MPN film for pre-grown silver seeds;

[0013] (3) The MPN membrane with pre-grown silver seeds was transferred to silver nitrate solution B and soaked for an appropriate time. Then the membrane was soaked in a reducing agent solution to reduce silver ions to silver nanoparticles. After washing, Ag@MPN composite membrane was obtained.

[0014] The mass concentration of silver nitrate solution B is greater than or equal to the mass concentration of silver nitrate solution A.

[0015] In one embodiment of the present invention, the porous support membrane includes a polysulfone ultrafiltration membrane, a polyethersulfone ultrafiltration membrane, a polyacrylonitrile ultrafiltration membrane, a hydrolyzed polyacrylonitrile ultrafiltration membrane, a cellulose acetate ultrafiltration membrane, etc. A polyacrylonitrile ultrafiltration membrane is preferred, and the porous support membrane is a porous support membrane washed with deionized water.

[0016] In one embodiment of the present invention, the polyphenol is one or more of tannic acid, dopamine, phytic acid, gallic acid, quercetin, pyrogallol, and epigallocatechin gallate. Tannic acid is preferred.

[0017] In one embodiment of the present invention, the reducing agent is sodium borohydride, sodium citrate, dimethylamine borane, ascorbic acid, etc. Dimethylamine borane is preferred.

[0018] In one embodiment of the present invention, in step (1), the soaking time of the polyphenol solution is 0 to 60 min, and is not 0; preferably 5 min.

[0019] In one embodiment of the present invention, in step (1), the time for oscillatory co-deposition is 60 to 360 minutes. Further, the co-deposition time is preferably 120 to 360 minutes.

[0020] In one embodiment of the present invention, in step (1), the temperature of the oscillating co-deposition is 10 to 60°C, and more preferably 25°C.

[0021] In one embodiment of the present invention, in step (1), the heat treatment temperature is 30–80°C, and the reaction time is 0–60 min. Further, the heat treatment temperature is 70°C, and the reaction time is preferably 10 min.

[0022] In one embodiment of the present invention, in step (1), the concentration of the polyphenol aqueous solution is 0.8–80 mg / mL. Further, the concentration of the polyphenol aqueous solution is preferably 0.8–8 mg / mL. Even more preferably, it is 4–8 mg / mL.

[0023] In one embodiment of the present invention, in step (1), the concentration of the ferrous salt aqueous solution is 0.98–98 mg / mL. Further, the concentration of the ferrous salt aqueous solution is preferably 9.8–98 mg / mL.

[0024] In one embodiment of the present invention, in step (1), the molar ratio of polyphenol to ferrous salt is 1:1 to 1:100. Further, the molar ratio of polyphenol to ferrous salt is preferably 1:10 to 20.

[0025] In one embodiment of the present invention, in step (2), the concentration of the silver nitrate solution A is 5–20 mmol / L. More preferably, it is 5–10 mmol / L.

[0026] In one embodiment of the present invention, in step (2), the pre-soaking time is 0 to 30 minutes, and is not 0 minutes. Further, the soaking time is preferably 5 to 15 minutes. Even further, it is 5 to 10 minutes.

[0027] In one embodiment of the present invention, in step (3), the concentration of the silver nitrate solution B is 10–50 mmol / L. More preferably, it is 10–25 mmol / L.

[0028] In one embodiment of the present invention, in step (3), the soaking time is 0 to 150 minutes, and is not 0 minutes. Further, the soaking time is preferably 15 to 30 minutes.

[0029] In one embodiment of the present invention, in step (3), the concentration of the reducing agent dimethylamine borane solution is 0.01–0.5 mmol / L. Further, the concentration of the dimethylamine borane solution is preferably 0.01–0.1 mmol / L.

[0030] In one embodiment of the present invention, in step (3), the reaction time is 0 to 120 min, and is not 0. Further, the reaction time is preferably 15 to 45 min. Even more preferably, it is 15 to 30 min.

[0031] In one embodiment of the present invention, the polyphenol aqueous solution is obtained by dissolving polyphenols in ultrapure water.

[0032] In one embodiment of the present invention, the ferrous salt aqueous solution is obtained by dissolving ferrous salt in ultrapure water.

[0033] In one embodiment of the present invention, the silver nitrate solution is obtained by dissolving silver nitrate in ultrapure water.

[0034] In one embodiment of the present invention, the reducing agent solution is obtained by dissolving dimethylamine borane in ultrapure water.

[0035] In one embodiment of the present invention, the MPN is a three-dimensional stable metal polyphenol network composed of polyphenols and metal ions coordinated together. It can be constructed within one minute and can form a separation layer. The resulting metal polyphenol coordination bonds possess advantages such as strong coordination, structural diversity, hydrolytic stability, and pH dependence. Because the catechol structure in the polyphenols can impart universal adhesion properties to the metal network through covalent / non-covalent interactions, it can adhere to the surfaces of materials with different morphologies and sizes, thus ensuring stable bonding between the coating and various supporting substrates.

[0036] In one embodiment of the present invention, surface-enhanced Raman scattering (SERS) is a special Raman scattering phenomenon that occurs only on the surface of special materials, typically Ag and Au. The generation and quality of the SERS signal are affected by the size, morphology, and interparticle spacing of the nanoparticles. A high-intensity localized electric field, i.e., a surface-enhanced Raman hotspot, is generated between noble metal nanoparticles. When molecules are located within this hotspot, strong Raman scattering occurs.

[0037] In one embodiment of the present invention, a metal polyphenol network is constructed on a porous support membrane to impart separation performance to the membrane, and silver nanoparticles are grown in situ on the MPN layer to impart surface-enhanced Raman detection performance to the membrane.

[0038] The present invention provides a composite nanofiltration membrane with surface-enhanced Raman detection function based on the above method.

[0039] The present invention also provides the application of the above-mentioned composite nanofiltration membrane with surface-enhanced Raman detection function in the field of drug separation and detection based on nanofiltration technology.

[0040] Beneficial effects:

[0041] (1) This invention integrates separation and detection, enabling the separation of drugs from harmful substances during the pharmaceutical process, and allowing for rapid in-situ detection of the effectiveness of the separation without sample preparation steps, thus simplifying the detection process. This detection method maintains the integrity and original characteristics of the sample, providing a reliable option for rapid analysis. Surface-enhanced Raman spectroscopy can accurately detect trace amounts of target substances in samples, improving the detection rate of harmful substances in drugs.

[0042] (2) This invention employs in-situ growth of silver nanoparticles, which enhances the coupling between the silver nanoparticles and the substrate film, thereby improving substrate stability and ensuring signal reliability and uniformity. Detection sensitivity is improved by adjusting reaction conditions such as the concentration and soaking time of the silver nitrate solution and the reduction time of dimethylamine borane.

[0043] (3) The materials and processes used in this invention are simple and easy to apply industrially. At the same time, the materials used are non-toxic, the reaction is carried out in an aqueous solution, and no harmful substances are introduced during the preparation of the substrate, which can ensure safety during the separation and detection process.

[0044] This invention employs nanofiltration separation technology and surface-enhanced Raman spectroscopy detection method to improve separation efficiency, shorten detection time, eliminate the need for preliminary preparation, and enable real-time in-situ detection during pharmaceutical manufacturing. Furthermore, the surface-enhanced Raman spectroscopy detection method can achieve trace detection of target analytes, thereby improving detection sensitivity. Attached Figure Description

[0045] Figure 1 Scanning electron microscope image of Ag@MPN composite film;

[0046] Figure 2 Surface-enhanced Raman spectra of methanol solutions of irbesartan, N-nitrosodimethylamine, and N-nitrosodiethylamine;

[0047] Figure 3 The image shows the Raman enhancement test results of the composite membrane after separation, which was doped with different concentrations of N-nitrosodimethylamine and N-nitrosodiethylamine in irbesartan solution. Detailed Implementation

[0048] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0049] The reagents used in the various embodiments of this invention are as follows: tannic acid, Sigma-Aldrich (USA); iron(II) chloride tetrahydrate, Sinopharm Chemical Reagent Co., Ltd.; silver nitrate (AgNO3), Sinopharm Chemical Reagent Co., Ltd.; dimethylamine borane, Shanghai Mairui Biochemical Technology Co., Ltd.

[0050] The porous support membrane used in the various embodiments of the present invention is a three-dimensional polyacrylonitrile ultrafiltration membrane (PAN, MWCO = 40 kDa) produced by Beijing Ande Membrane Separation Technology Co., Ltd.

[0051] The composite nanofiltration membrane prepared in this invention is used for the separation and detection of irbesartan. Flux, surface-enhanced Raman characteristic peak distribution, and characteristic peak intensity are two important parameters for evaluating the separation and detection performance of nanofilms.

[0052] The organic phase nanofiltration performance of the composite membrane was evaluated using dead-end filtration and Raman spectroscopy. Before testing, the composite membrane was pre-compressed with methanol as the feed solution for 30 minutes to stabilize its performance. A 1 g / L irbesartan methanol solution doped with 100 mg / L N-nitrosodimethylamine and 100 mg / L N-nitrosodiethylamine was used as the feed solution. Filtration performance was tested at 0.3 MPa. The organic phase nanofiltration performance of the composite nanofiltration membrane was evaluated by recording the permeate flux. Raman spectroscopy was performed on the composite membrane, and the distribution and intensity of characteristic peaks were recorded to evaluate the separation effectiveness and retention performance of the composite nanofiltration membrane.

[0053] The permeation flux (J) of the composite membrane is defined as follows:

[0054] J=V / (A×t×ΔP) (1)

[0055] Where V represents the filtrate volume in L; A represents the tested area of ​​the nanocomposite membrane in m². 2 t represents the time required to collect the corresponding filtrate, in hours (h), and ΔP represents the pressure applied to the surface of the nanocomposite membrane, in bars (1 MPa = 10 bar).

[0056] The separation factor (S) of the composite membrane is defined as follows:

[0057]

[0058] Among them, C H,p and C H,f C represents the concentration of harmful substances (N,N-nitrosodimethylamine and N,N-nitrosodiethylamine) in the permeate and feed liquid. I,p and C I,f This indicates the concentration of irbesartan in the permeate and feed solutions.

[0059] Example 1

[0060] (1) Weigh an appropriate amount of tannic acid and dissolve it in 30 mL of ultrapure water to obtain a polyphenol aqueous solution with a polyphenol concentration of 8 mg / mL; weigh an appropriate amount of ferrous chloride tetrahydrate and dissolve it in 30 mL of ultrapure water to obtain a ferrous salt aqueous solution with a ferrous chloride concentration of 9.8 mg / mL. Immerse the polyacrylonitrile ultrafiltration membrane in the polyphenol aqueous solution for 5 min; then add the ferrous salt aqueous solution and quickly transfer it to a water bath constant temperature shaker, and shake and co-deposit at 25℃ for 120 min; after co-deposition, transfer it to an oven and react at 70℃ for 10 min. Finally, take out the membrane and wash it with ultrapure water to obtain a membrane with an MPN layer.

[0061] (2) Weigh an appropriate amount of silver nitrate and dissolve it in 30 mL of ultrapure water to obtain a silver nitrate solution of 0.01 mol / L. Immerse the membrane obtained in step (1) in the silver nitrate aqueous solution for 5 min and grow silver seeds on the MPN layer in advance.

[0062] (3) Weigh an appropriate amount of silver nitrate and dissolve it in 30 mL of ultrapure water to obtain a silver nitrate solution of 0.025 mol / L. Immerse the membrane obtained in step (2) in the silver nitrate solution for 30 min.

[0063] (4) Weigh an appropriate amount of dimethylamine borane and dissolve it in 850 mL of ultrapure water to obtain a 0.1 mmol / L dimethylamine borane solution. Immerse the membrane obtained in step (3) in the dimethylamine borane solution to reduce silver ions and achieve in-situ growth of silver nanoparticles. Finally, remove the membrane and wash it with ultrapure water to obtain the Ag@MPN composite membrane.

[0064] Figure 1 This indicates the successful synthesis of the Ag@MPN composite membrane.

[0065] Figure 2 This indicates that Raman testing using the prepared Ag@MPN composite film can distinguish the three substances by the position of the characteristic peaks. It can also be seen that the deposited MPN layer has no Raman peaks and has no effect on the surface-enhanced Raman detection of the target analyte.

[0066] Examples 2-6

[0067] The concentration of tannic acid in the solution was adjusted (as shown in Table 1), and the other conditions were the same as in Example 1 to obtain the Ag@MPN composite membrane.

[0068] The Ag@MPN composite membranes prepared in Examples 2-6 were tested. The results are shown in Table 1.

[0069] Table 1. Flux and separation factor results of Ag@MPN composite membranes prepared in Examples 1-6

[0070]

[0071] As shown in Table 1, with the increase of tannic acid concentration, the pH value in the reaction solution decreases because tannic acid solution is acidic, which leads to an increase in the flux of the MPN separation layer and a continuous decrease in the separation factor.

[0072] Examples 7-11

[0073] The concentration of ferrous chloride in the solution was adjusted (as shown in Table 2), and the other implementation conditions were the same as in Example 1, to obtain the Ag@MPN composite membrane.

[0074] The Ag@MPN composite membranes prepared in Examples 7-11 were tested. The results are shown in Table 2.

[0075] Table 2. Flux and separation factor results of Ag@MPN composite membranes prepared in Examples 7-11

[0076]

[0077] As shown in Table 2, with the increase of ferrous chloride concentration, the Ag@MPN composite membrane becomes more compact, resulting in a decrease in the flux of the composite membrane and a continuous increase in the separation factor until it stabilizes.

[0078] Examples 12-16

[0079] Adjust the co-deposition time (as shown in Table 3), and keep the other implementation conditions the same as in Example 1 to obtain the Ag@MPN composite film.

[0080] The Ag@MPN composite membranes prepared in Examples 12–16 were tested. The results are shown in Table 3.

[0081] Table 3. Flux and separation factor results of Ag@MPN composite membranes prepared in Examples 12-16

[0082]

[0083] As shown in Table 3, the flux of the composite membrane decreases with the extension of deposition time, which is due to the continuous increase in the thickness of the separation layer. With a long deposition time, the drug separation factor increases continuously, partly due to the complete formation and compactness of the separation layer, and partly due to the increase in thickness while the compactness of the separation layer remains unchanged, which leads to a continuous increase in the separation factor.

[0084] Examples 17-19

[0085] Adjust the concentration of the silver nitrate solution in step (2) as shown in Table 4, and the remaining implementation conditions are the same as in Example 1.

[0086] The Ag@MPN composite membranes prepared in Examples 17–19 were tested. The results are shown in Table 4.

[0087] Table 4. Flux, separation factor, and characteristic peak intensity results of the Ag@MPN composite membranes prepared in Examples 17-19.

[0088]

[0089] The surface-enhanced Raman spectroscopy (SERS) used an excitation wavelength of 532 nm, an excitation power of 1 mW, and an excitation time of 10 s. (1619 cm⁻¹) -1 The absorption peak at this point represents the NC and NN stretching vibrations of the tetrazolium ring in irbesartan. Since this absorption peak has the highest intensity, it is selected as the representative characteristic peak intensity.

[0090] As shown in Table 4, changes in the concentration of pre-soaked silver nitrate affect the growth of silver nanoparticles grown in situ in step (3). With the increase of the concentration of the pre-soaked silver nitrate solution, the particle size of silver nanoparticles increases, the flux and separation factor decrease, and the intensity of characteristic peaks also decreases.

[0091] Examples 19-23

[0092] Adjust the pre-soaking time of silver nitrate solution in step (2) as shown in Table 5, and the other implementation conditions are the same as in Example 1.

[0093] The Ag@MPN composite membranes prepared in Examples 19–23 were tested. The results are shown in Table 5.

[0094] Table 5. Flux, separation factor, and characteristic peak intensity results of the Ag@MPN composite membranes prepared in Examples 19-23.

[0095]

[0096] As shown in Table 5, with the increase of the pre-soaking time of silver nitrate, the particle size of the silver nanoparticles in the prepared composite membrane will increase, resulting in a continuous decrease in flux and separation factor, and a continuous decrease in the intensity of characteristic peaks.

[0097] Examples 24-27

[0098] Adjust the concentration of the silver nitrate solution in step (3) as shown in Table 6, and the remaining implementation conditions are the same as in Example 1.

[0099] The Ag@MPN composite membranes prepared in Examples 24–27 were tested. The results are shown in Table 6.

[0100] Table 6. Flux, separation factor, and characteristic peak intensity results of the Ag@MPN composite membranes prepared in Examples 24-27.

[0101]

[0102] Table 6 shows that the MPN layer exhibits excellent separation performance, effectively separating drugs and harmful substances with a separation factor exceeding 95%. When the silver nitrate solution is at a low concentration, the silver nanoparticles on the membrane surface are small in size and have a large interparticle spacing, resulting in high flux. Increasing the silver nitrate solution concentration increases the particle size of the silver nanoparticles on the composite membrane surface, leading to an increase in membrane thickness. The silver nanoparticles may clog the membrane pores, thus reducing the flux of the composite membrane. The table also shows that the characteristic peak intensity of irbesartan is low at both low and high concentrations. This is because excessively large or small silver nanoparticles may prevent the generation of sufficient Raman hot spots, reducing the Raman detection signal.

[0103] Examples 28-30

[0104] Adjust the soaking time of the silver nitrate solution in step (3), and the other implementation conditions are the same as in Example 1.

[0105] The Ag@MPN composite membranes prepared in Examples 28–30 were tested. The results are shown in Table 7.

[0106] Table 7. Flux, separation factor, and characteristic peak intensity results of the Ag@MPN composite membranes prepared in Examples 28-30.

[0107]

[0108] As shown in Table 7, the flux decreases continuously with prolonged immersion time. This is because the particle size of silver nanoparticles increases, and the thickness of the composite membrane increases, which may clog the membrane pores. The intensity of the characteristic peaks shows a trend of first increasing and then decreasing because with prolonged immersion time, the particle size of silver nanoparticles on the surface of the composite membrane becomes too large or too small, and insufficient hot spots are generated at the interparticle spacing, which reduces the Raman detection signal.

[0109] Examples 31-34

[0110] Adjust the concentration of the reducing agent dimethylborane in step (3), and the remaining implementation conditions are the same as in Example 1.

[0111] The Ag@MPN composite membranes prepared in Examples 31-34 were tested. The results are shown in Table 8.

[0112] Table 8. Flux, separation factor, and characteristic peak intensity results of the Ag@MPN composite membranes prepared in Examples 31-34.

[0113]

[0114] As shown in Table 8, with the increase of dimethylborane concentration, the particle size of silver nanoparticles increases, which may block the membrane pores, leading to a decrease in the flux of the composite membrane and a continuous decrease in the separation factor. The particle size of silver nanoparticles affects the generation of Raman hotspots, and the intensity of the characteristic peaks shows a trend of first increasing and then decreasing.

[0115] Examples 35-39

[0116] Adjust the reduction time of the reducing agent dimethylborane in step (3), and the other implementation conditions are the same as in Example 1.

[0117] The Ag@MPN composite membranes prepared in Examples 35–39 were tested. The results are shown in Table 9.

[0118] Table 9. Flux, separation factor, and characteristic peak intensity results of the Ag@MPN composite membranes prepared in Examples 35-39.

[0119]

[0120] As shown in Table 9, the particle size of silver nanoparticles increases with the extension of reduction time, which may clog pores and cause the flux and separation factor to decrease continuously. The change in the particle size of silver nanoparticles cannot generate enough Raman hot spots, which leads to a decrease in the intensity of characteristic peaks.

[0121] Examples 40-43: Separation and quantitative detection of nitrosamines, a type of genotoxic substance, based on Ag@MPN composite membranes.

[0122] (1) An Ag@MPN composite membrane was prepared according to the method in Example 1.

[0123] (2) Separation and quantitative detection of nitrosamines, a genetically harmful substance, based on this Ag@MPN composite membrane:

[0124] Before testing, the composite membrane needs to be pre-pressed with methanol as the raw material for 30 minutes to stabilize its performance.

[0125] Using irbesartan methanol solution with a concentration of 1 g / L, N-nitrosodimethylamine and N-nitrosodiethylamine of different concentrations were doped as raw materials. The mixture was filtered at a pressure of 0.3 MPa, and the composite membrane was then subjected to Raman spectroscopy. The results are shown in Table 10.

[0126] Table 10. Flux, separation factor, and characteristic peak intensity results of the Ag@MPN composite membranes prepared in Examples 40-43.

[0127]

[0128] As shown in Table 10, the Ag@MPN composite membrane prepared by this method has excellent separation performance, and exhibits superior separation performance for harmful substances at low concentrations.

[0129] The concentrations of harmful substances (10-200 mg / L) and the corresponding Raman peak intensities were linearly fitted, and the results are as follows: Figure 3 As shown. By Figure 3 As can be seen, when different concentrations of harmful substances (N-nitrosodimethylamine and N-nitrosodiethylamine) are doped into the irbesartan solution, the intensity of the Raman characteristic peak decreases with decreasing concentration of the harmful substance, and there is a strong linear relationship between the concentration of the harmful substance and the intensity of the characteristic peak. 2 The value of 0.98 indicates that this method can be used to quantitatively detect harmful substances in irbesartan, which helps to better ensure the quality of the drug and the safety of its use.

[0130] The embodiments provided above are not intended to limit the scope of the invention, nor are the described steps intended to limit the order of execution. Any obvious modifications made to the invention by those skilled in the art based on existing common knowledge also fall within the scope of protection defined by the claims.

Claims

1. A method for preparing a composite nanofiltration membrane with surface-enhanced Raman detection function, characterized in that, Includes the following steps: (1) The porous support membrane is first soaked in a polyphenol solution, then an aqueous solution of ferrous salt is added, and the membrane is shaken and co-deposited. After heat treatment, a membrane with MPN is obtained. (2) The membrane with the MPN layer is immersed in silver nitrate solution A to obtain the MPN membrane with pre-grown silver seeds; (3) The MPN membrane with pre-grown silver seeds was transferred to silver nitrate solution B for soaking, and then the membrane was immersed in the reducing agent dimethylamine borane solution to achieve in-situ growth of silver nanoparticles; finally, the membrane was taken out and washed with ultrapure water to obtain a composite nanofiltration membrane. The concentration of silver nitrate solution B is greater than or equal to the concentration of silver nitrate solution A; The porous support membrane is one of polysulfone ultrafiltration membrane, polyethersulfone ultrafiltration membrane, polyacrylonitrile ultrafiltration membrane, hydrolyzed polyacrylonitrile ultrafiltration membrane, and cellulose acetate ultrafiltration membrane; the polyphenol is one or more of tannic acid, gallic acid, quercetin, pyrogallol, and epigallocatechin gallate.

2. The preparation method according to claim 1, characterized in that, In step (2), the concentration of the silver nitrate solution A is 5–20 mmol / L.

3. The preparation method according to claim 1, characterized in that, In step (3), the concentration of silver nitrate solution B is 10-50 mmol / L.

4. The preparation method according to claim 1, characterized in that, The ferrous salt is one or more of ferrous chloride, ferrous chloride tetrahydrate, ferrous sulfate, and ferrous bromide.

5. The preparation method according to claim 1, characterized in that, In step (1), the time for which the porous support membrane is immersed in the polyphenol solution is 0 to 60 min, and not 0; the time for the oscillating co-deposition is 60 to 360 min, the reaction temperature is 10 to 60 °C, the heat treatment temperature is 30 to 80 °C, and the reaction time is 0 to 60 min.

6. The preparation method according to claim 1, characterized in that, In step (1), the concentration of the polyphenol solution is 0.8 to 80 mg / mL, the concentration of the ferrous salt aqueous solution is 0.98 to 98 mg / mL, and the molar ratio of polyphenol to ferrous salt is 1:1 to 1:

100.

7. The preparation method according to claim 1, characterized in that, In step (2), the soaking time is 0 to 30 min and is not 0; in step (3), the soaking time is 0 to 150 min and is not 0.

8. The preparation method according to claim 1, characterized in that, In step (3), the concentration of the reducing agent dimethylamine borane solution is 0.01~0.5 mmol / L, and the reaction time is 0~120 min, and is not 0.

9. A composite nanofiltration membrane with surface-enhanced Raman detection function prepared by the preparation method according to any one of claims 1-8.

10. The application of the composite nanofiltration membrane according to claim 9 in drug separation and detection.

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