A molecular imprinting material for paclitaxel adsorption and preparation method thereof

Abstract

The present invention provides a molecular imprinting material for paclitaxel adsorption and a preparation method thereof, which mainly comprises the following steps: (1) preparation of cellulose microspheres, (2) preparation of modified cellulose microspheres, and (3) preparation of molecular imprinting material. The molecular imprinting material prepared by the present invention in a limited manner has good selective adsorption of paclitaxel, and also has good mechanical properties, hydrophobicity, and reusability.

Description

Technical Field

[0001] The invention belongs to the field of polymer materials, and particularly relates to a molecular imprinting material for paclitaxel adsorption and a preparation method thereof. Background Art

[0002] Paclitaxel is a unique diterpene compound extracted from Taxus chinensis. It has a good anti-cancer effect on ovarian cancer and breast cancer, and also has special therapeutic effects on lung cancer, colon cancer and melanoma. In order to ensure the quality of the extract, its components need to be tested in a timely manner. However, the content of paclitaxel in Taxus chinensis is very low, and Taxus chinensis contains structural analogs and other impurities with complex components. Therefore, it is very difficult to extract and determine paclitaxel in Taxus chinensis.

[0003] Although many analytical instruments with high sensitivity and selectivity have been developed, complex pretreatment steps are usually required to extract, separate and pre-concentrate the analytes, which is a time-consuming task, and the sample treatment effect has a great impact on the final analysis results. Solid phase extraction is a technology that uses adsorbents to extract target molecules from a given sample, but most materials used for solid phase extraction are not selective for the analytes. Molecularly imprinted materials, as an effective adsorbent, can solve the above problems through the "lock and key" principle, making them a promising alternative to traditional adsorbents. However, molecularly imprinted carriers are currently mostly chemically synthesized, which is difficult to degrade, has cumbersome synthesis steps, and is a rare carrier with low economic value, which is not conducive to large-scale development. Summary of the invention

[0004] In view of the above problems in the prior art, the present invention provides a molecular imprinting material for paclitaxel adsorption and a preparation method thereof, with the aim of using non-toxic and inexpensive cellulose as a raw material to prepare a molecular imprinting material with selective adsorption of paclitaxel.

[0005] To achieve the above object, the present invention adopts the following technical solutions: A molecular imprinting material for paclitaxel adsorption and a preparation method thereof. The preparation method of the molecular imprinting material comprises the following steps: (1) Preparation of cellulose microspheres: After the prepared solution A is mixed evenly with dimethyl sulfoxide, microcrystalline cellulose is added and stirred at 95-105°C until completely dissolved. Sodium bicarbonate and epichlorohydrin are added at 22-28°C and stirred for 30-60 min. The mixture is transferred to a glass mold and allowed to stand at 8-12°C for 10-14 h for gelation. The obtained gel is then sieved through a 100-120 mesh sieve to prepare microspheres. The microspheres are then immersed in a 5 wt% hydrochloric acid solution and allowed to stand for 8-16 h. Finally, the microspheres are washed with deionized water for 3-5 times to obtain cellulose microspheres. (2) Preparation of modified cellulose microspheres: 20 wt% acetic acid aqueous solution, anhydrous ethanol, and 3-(methacryloyloxy)propyltrimethoxysilane (MPS) were mixed evenly and stirred at 55-65°C for 1-1.5 h, and then the cellulose microspheres prepared in step (1) were added, and the temperature was kept constant and stirred for 3-4 h. The solid was filtered and rinsed with deionized water for 3-5 times to obtain modified cellulose microspheres; (3) Preparation of molecular imprinting material: Paclitaxel, acrylamide (AM) and methanol were mixed evenly and stirred at 22-28°C in the dark for 12-14 h. The modified cellulose microspheres prepared in step (2), divinylbenzene (DVB), trimethylolpropane trimethacrylate (TMPTMA) and azobisisobutyronitrile (AIBN) were then added to the mixture, and the mixture was magnetically stirred at 60-70°C in the dark for 22-26 h under nitrogen protection. Finally, the solid was eluted with an eluent for 5-6 times to remove paclitaxel, and the solid was washed with methanol for 3-5 times to remove acetic acid, thereby obtaining a molecular imprinting material with specific adsorption effect on paclitaxel.

[0006] Preferably, the preparation method of solution A in step (1) is as follows: a strongly alkaline organic reagent and a carboxylic acid are uniformly mixed in a molar ratio of 2:1, and stirred at 85-95° C. until a clear liquid is obtained, and then continued to stir for 3-4 hours.

[0007] Preferably, the microcrystalline cellulose in step (1) is ball-milled, and the ball-milling conditions are a ball-to-material ratio of 30:1, a rotation speed of 300-500 rpm / min, and a time of 5-6 h.

[0008] Preferably, in step (1), the ratio of the mass (g) of microcrystalline cellulose, sodium bicarbonate, dimethyl sulfoxide, solution A and the volume (mL) of epichlorohydrin is 1: (0.2-0.3): (7-10): (28-40): (0.45-0.55).

[0009] Preferably, in step (2), the volume ratio of acetic acid aqueous solution, anhydrous ethanol, and 3-(methacryloyloxy)propyltrimethoxysilane (MPS) is 1:(5-8):(0.24-0.28), and the ratio of the mass (g) of cellulose microspheres to the volume (mL) of 3-(methacryloyloxy)propyltrimethoxysilane (MPS) is 1:(1.2-1.5).

[0010] Preferably, in the reaction of step (3), the molar ratio of paclitaxel, acrylamide (AM), divinylbenzene (DVB), trimethylolpropane trimethacrylate (TMPTMA), and azobisisobutyronitrile (AIBN) is 1: (12-14): (28-32): (28-32): (1.8-2.2), and the ratio of the volume (mL) of methanol, the mass (mg) of modified cellulose microspheres, and the mass (mg) of acrylamide (AM) is 1: (17-20): (1-1.4).

[0011] Preferably, the eluent in step (3) is prepared from methanol and acetic acid, wherein the volume ratio of methanol to acetic acid is 9:1.

[0012] Preferably, the strong alkaline organic reagent is one of 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and the carboxylic acid is one of citric acid, glutaric acid and adipic acid.

[0013] Compared with the prior art, the present invention has the following beneficial effects: The molecular imprinted material prepared by the present invention in a limited manner has good mechanical properties and hydrophobicity, and has good selective adsorption of paclitaxel. The adsorption amount of paclitaxel can reach more than 36 mg / g within 60 minutes, and the desorption rate can reach more than 83% within 10 minutes. In addition, the molecular imprinted material has good reusability. After repeating the adsorption experiment seven times, its reusability can still reach more than 90%.

[0014] Other advantages, objectives and features of the present invention will be embodied in part through the following description, and in part will be understood by those skilled in the art through study and practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The hydrophilic and hydrophobic properties test results of the embodiments and comparative examples are shown in FIG. Figure 2 The solid phase extraction column is loaded with the molecular imprinting material of Example 1. DETAILED DESCRIPTION

[0016] The present invention is specifically described below by way of examples, which are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. It should be understood that after reading the contents of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application.

[0017] Example 1 (1) Preparation of cellulose microspheres: 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and citric acid were mixed at a molar ratio of 2:1, stirred at 90°C until a clear liquid was obtained, and then stirred for 3 hours to obtain solution A. 80 g of the prepared solution A was mixed with 20 g of dimethyl sulfoxide, and then 2.5 g of microcrystalline cellulose (ball milled for 5 hours at a ball-to-material ratio of 30:1 and a rotation speed of 400 rpm / min) was added and stirred at 100°C until completely dissolved. Then, 0.6 g of sodium bicarbonate and 1.25 mL of epichlorohydrin were added at 25°C and stirred for 40 minutes, and then transferred to a glass mold, and allowed to stand at 10°C for 12 hours for gelation. The obtained gel was then sieved through a 110-mesh sieve to prepare microspheres, and the microspheres were immersed in a 5 wt% hydrochloric acid solution and allowed to stand for 12 hours. Finally, the microspheres were washed 4 times with deionized water to obtain cellulose microspheres. (2) Preparation of modified cellulose microspheres: 15 mL of 20 wt% acetic acid aqueous solution, 90 mL of anhydrous ethanol, and 4 mL of 3-(methacryloyloxy)propyltrimethoxysilane (MPS) were mixed evenly and stirred at 60 °C for 1.2 h. Then, 3 g of the cellulose microspheres prepared in step (1) were added. The temperature was kept constant and stirring was continued for 3 h. The solid was filtered and rinsed with deionized water 4 times to obtain modified cellulose microspheres. (3) Preparation of molecular imprinting material: 0.05 mmol paclitaxel, 0.65 mmol acrylamide (AM) and 40 mL methanol were mixed evenly and stirred at 25 °C in the dark for 13 h. Then, 750 mg of modified cellulose microspheres prepared in step (2), 1.5 mmol divinylbenzene (DVB), 1.5 mmol trimethylolpropane trimethacrylate (TMPTMA) and 0.1 mmol azobisisobutyronitrile (AIBN) were added to the mixture, respectively. The mixture was magnetically stirred at 65 °C in the dark for 24 h under nitrogen protection. Finally, the solid was eluted with an eluent (methanol and acetic acid in a volume ratio of 9:1) for 5 times to remove paclitaxel, and the solid was washed with methanol for 4 times to remove acetic acid, thereby obtaining a molecular imprinting material with specific adsorption effect on paclitaxel.

[0018] Example 2 (1) Preparation of cellulose microspheres: 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and glutaric acid were mixed at a molar ratio of 2:1, stirred at 85°C until a clear liquid was obtained, and then stirred for 3 hours to obtain solution A. 70 g of the prepared solution A was mixed with 17.5 g of dimethyl sulfoxide, and then 2.5 g of microcrystalline cellulose (ball milled at a ball-to-material ratio of 30:1 and a rotation speed of 300 rpm / min for 6 hours) was added and stirred at 95°C until completely dissolved. Then, 0.5 g of sodium bicarbonate and 1.13 mL of epichlorohydrin were added at 22°C and stirred for 30 minutes, and then transferred to a glass mold, and allowed to stand at 8°C for 10 hours for gelation. The obtained gel was then sieved through a 100-mesh sieve to prepare microspheres, and the microspheres were immersed in a 5 wt% hydrochloric acid solution and allowed to stand for 8 hours. Finally, the microspheres were washed with deionized water for 3 times to obtain cellulose microspheres. (2) Preparation of modified cellulose microspheres: 15 mL of 20 wt% acetic acid aqueous solution, 75 mL of anhydrous ethanol, and 3.6 mL of 3-(methacryloyloxy)propyltrimethoxysilane (MPS) were mixed evenly and stirred at 55 °C for 1 h. Then 3 g of the cellulose microspheres prepared in step (1) were added and the temperature was kept constant and stirred for 3 h. The solid was filtered and rinsed with deionized water for 3 times to obtain modified cellulose microspheres. (3) Preparation of molecular imprinting material: 0.05 mmol paclitaxel, 0.6 mmol acrylamide (AM) and 40 mL methanol were mixed evenly and stirred at 22 °C in the dark for 12 h. Then, 680 mg of modified cellulose microspheres prepared in step (2), 1.4 mmol divinylbenzene (DVB), 1.4 mmol trimethylolpropane trimethacrylate (TMPTMA) and 0.09 mmol azobisisobutyronitrile (AIBN) were added to the mixture, and the mixture was magnetically stirred at 60 °C in the dark for 22 h under nitrogen protection. Finally, the solid was eluted with an eluent (methanol and acetic acid in a volume ratio of 9:1) for 5 times to remove paclitaxel, and the solid was washed with methanol for 3 times to remove acetic acid, thereby obtaining a molecular imprinting material with specific adsorption effect on paclitaxel.

[0019] Example 3 (1) Preparation of cellulose microspheres: 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and adipic acid were mixed at a molar ratio of 2:1, stirred at 95°C until a clear liquid was obtained, and then stirred for 4 hours to obtain solution A. 100 g of the prepared solution A was mixed with 25 g of dimethyl sulfoxide, and then 2.5 g of microcrystalline cellulose (ball milled for 5 hours at a ball-to-material ratio of 30:1 and a rotation speed of 500 rpm / min) was added and stirred at 105°C until completely dissolved. Then, 0.75 g of sodium bicarbonate and 1.37 mL of epichlorohydrin were added at 28°C, stirred for 60 minutes, and transferred to a glass mold. The mixture was allowed to stand at 12°C for 14 hours for gelation, and then the obtained gel was passed through a 120-mesh sieve to prepare microspheres. The microspheres were immersed in a 5 wt% hydrochloric acid solution and allowed to stand for 16 hours. Finally, they were washed with deionized water for 5 times to obtain cellulose microspheres. (2) Preparation of modified cellulose microspheres: 16.5 mL of 20 wt% acetic acid aqueous solution, 132 mL of anhydrous ethanol, and 4.5 mL of 3-(methacryloyloxy)propyltrimethoxysilane (MPS) were mixed evenly and stirred at 65 °C for 1.5 h. Then, 3 g of the cellulose microspheres prepared in step (1) were added. The temperature was maintained constant and stirring was continued for 4 h. The solid was filtered and rinsed with deionized water 5 times to obtain modified cellulose microspheres. (3) Preparation of molecular imprinting material: 0.05 mmol paclitaxel, 0.7 mmol acrylamide (AM) and 36 mL methanol were mixed evenly and stirred at 28 °C in the dark for 14 h. Then, 720 mg of modified cellulose microspheres prepared in step (2), 1.6 mmol divinylbenzene (DVB), 1.6 mmol trimethylolpropane trimethacrylate (TMPTMA) and 0.11 mmol azobisisobutyronitrile (AIBN) were added to the mixture, and the mixture was magnetically stirred at 70 °C in the dark for 26 h under nitrogen protection. Finally, the solid was eluted with an eluent (methanol and acetic acid in a volume ratio of 9:1) for 6 times to remove paclitaxel, and the solid was washed with methanol for 5 times to remove acetic acid, thereby obtaining a molecular imprinting material with specific adsorption effect on paclitaxel.

[0020] Comparative Example 1 The difference between the preparation method of the non-imprinted microspheres and that of Example 1 is that no paclitaxel template molecule is added in step (3), and the remaining steps are consistent with those of Example 1.

[0021] Comparative Example 2 The molecularly imprinted material made of unmodified cellulose microspheres: (1) Preparation of cellulose microspheres: the same as step (1) of Example 1; (2) Preparation of molecular imprinting material: The modified cellulose microspheres in step (3) of Example 1 were replaced with the cellulose microspheres prepared above, and the rest were the same as step (3) of Example 1.

[0022] Comparative Example 3 The preparation steps of the molecularly imprinted microspheres are as follows: (1) Preparation of cellulose microspheres: After 20 g of tetrabutylammonium fluoride and 80 g of dimethyl sulfoxide were mixed evenly, 2.5 g of microcrystalline cellulose was added and stirred at 100 °C until completely dissolved. Then, 0.6 g of sodium bicarbonate and 1.25 mL of epichlorohydrin were added at 25 °C and stirred for 40 min. The mixture was transferred to a glass mold and allowed to stand at 10 °C for 12 h for gelation. The obtained gel was then sieved through a 110 mesh sieve to prepare microspheres. The microspheres were then immersed in a 5 wt % hydrochloric acid solution and allowed to stand for 12 h. Finally, the microspheres were washed four times with deionized water to obtain cellulose microspheres. (2) Preparation of modified cellulose microspheres: the same as step (2) of Example 1; (3) Preparation of molecular imprinting material: the same as step (3) of Example 1.

[0023] Test methods and results Adsorption effect test: 1. Adsorption capacity and desorption rate test: (1) Adsorption capacity test: 20 mg of the adsorbent material was immersed in 10 mL of 0.2 mg / mL paclitaxel methanol solution (pH controlled at 7, temperature at 25°C), and the supernatant was taken at intervals to determine the paclitaxel concentration by HPLC, and the adsorption capacity was calculated by combining the formula. The formula is Q=(C1-C2)V / M, where Q is the adsorption capacity (mg / g), C1 is the initial paclitaxel concentration, C2 is the paclitaxel concentration when the adsorption equilibrium is reached, V is the volume of the standard solution used, and M is the mass of the adsorbent material (g).

[0024] Table 1 shows the test results of the paclitaxel adsorption amount of the embodiment and the comparative example. The data show that when the adsorption pH is 7 and the temperature is 25°C, the adsorption materials of the embodiment and the comparative example reach adsorption equilibrium at 60 minutes, and the adsorption amount of the embodiment 1 to 3 reaches more than 36 mg / g, which is significantly higher than the comparative example 1, indicating that the modified cellulose microspheres prepared by the present invention effectively form a cavity for paclitaxel. In addition, the adsorption amount of the embodiment 1 to 3 is higher than that of the comparative example 2, which may be because the hydrophobicity of the embodiment 1 to 3 is enhanced after the silane modification, which improves its stability in the adsorption environment on the one hand, and reduces the repulsive force between the hydrophobic paclitaxel and the hydrophobic paclitaxel on the other hand, thereby improving the adsorption capacity of the embodiment 1 to 3 for paclitaxel.

[0025] Table 1 Test results of paclitaxel adsorption in Examples and Comparative Examples (mg / g) (2) Desorption rate test: After eluting the adsorbed material, the paclitaxel concentration in the eluate was detected by HPLC and the desorption rate D was calculated. r (%), D r =C D V D / (C0-C T )V T , where C0 (mg / mL) and C T are the initial concentration and equilibrium concentration of paclitaxel in the solution during the adsorption process, C D The equilibrium concentration of paclitaxel in the solution during the desorption process, V T (mL) and V D (mL) is the volume of paclitaxel methanol solution during the adsorption and desorption processes.

[0026] Table 2 shows the test results of paclitaxel desorption rate of the examples and comparative examples. The data show that the desorption rates of Examples 1 to 3 can reach more than 83% within 10 minutes, while the desorption rate of Comparative Example 1 can only reach 38%, indicating that the molecular imprinted material prepared by the present invention has good desorption performance.

[0027] Table 2 Test results of paclitaxel desorption rate in Examples and Comparative Examples (%) 2. Specific adsorption test: prepare 10 mL of a methanol mixed solution (pH controlled at 7, temperature at 25°C) with paclitaxel, 10-deacetylbaccatin III (10-DAB), and Baccatin III at a concentration of 0.2 mg / mL, take 20 mg of the adsorption material and soak it in the above solution for 60 min, then take it out and measure and calculate the adsorption amount of paclitaxel.

[0028] Table 3 shows the specific adsorption test results of paclitaxel in the examples and comparative examples. The data show that the adsorption effects of the comparative example on paclitaxel, 10-deacetylbaccatin III (10-DAB) and baccatin III are similar, and the adsorption amounts are all lower than those of examples 1 to 3. However, the adsorption amounts of paclitaxel by the molecular imprinting materials prepared in examples 1 to 3 are significantly higher than those of the other two substances. Therefore, the molecular imprinting materials prepared in the present invention have good specific adsorption effects on paclitaxel and can avoid interference from other substances with similar structures in the mixture.

[0029] Table 3 Specific adsorption test results of paclitaxel in Examples and Comparative Examples (mg / g) 3. Reusability: Soak 10 mg of the adsorption material in 5 mL of 0.2 mg / mL paclitaxel methanol solution (pH controlled at 7, temperature at 25°C), and calculate the adsorption amount after 60 minutes. After the adsorption is completed, use the eluent to elute the paclitaxel, remove the eluent with acetonitrile, and then conduct the adsorption experiment again. Repeat 7 times and calculate the reuse rate R (%). R=Q1 / Q n , where Q1 (mg / g) is the first adsorption amount, Q n (mg / g) is the adsorption amount after the nth repetition.

[0030] Table 4 shows the test results of the reusability of the examples and comparative examples. The data show that examples 1 to 3 have good reusability. After seven repeated adsorption experiments, the reusability of molecular imprinting is above 90%, which is generally maintained at a high level. The main reason for the decrease in adsorption is that the adsorption material will be damaged to a certain extent after multiple elutions, which in turn affects its adsorption amount. The reusability of comparative example 3 is significantly lower than that of examples 1 to 3, which may be because the mechanical properties of comparative example 3 are poor and the degree of damage in repeated adsorption experiments is relatively large.

[0031] Table 4 Reusability test results of examples and comparative examples (%) 4. Contact angle test: After preparing a hydrogel film made of the same raw material as the microspheres according to steps (1) and (2) of Examples 1 to 3 and step (1) of Comparative Example 2, the hydrophilicity and hydrophobicity of the material were analyzed using a contact angle meter.

[0032] Table 5 Figure 1 The data show that the comparative example 2 is not modified with 3-(methacryloyloxy)propyltrimethoxysilane (MPS) and is hydrophilic with a static contact angle of 33.0, while the hydrophobicity of the examples 1 to 3 is enhanced after silanization modification, and the static contact angles are increased to 101.5, 103.3, and 103.6, respectively, so that the examples 1 to 3 can avoid the attachment of water-soluble impurities in a complex adsorption environment, laying a foundation for the selective adsorption of hydrophobic paclitaxel.

[0033] Table 5 Hydrophilic and hydrophobic properties test results of examples and comparative examples 5. Mechanical property test: After preparing hydrogel films made of the same raw materials as the microspheres according to steps (1) and (2) of Examples 1 to 3 and Comparative Example 3, a universal testing machine was used to measure the tensile strength and elongation at break of the samples at a constant tensile speed of 10 mm / min. Before the test, the samples were cut into rectangular strips of 50 mm in length and 10 mm in width, and then clamped in the instrument with two clamps. The initial distance between the two clamps was set to 20 mm. Five samples of each film were taken for tensile testing to obtain the average value of the tensile parameters.

[0034] Table 6 shows the mechanical property test results of the embodiments and comparative examples. The data show that the mechanical properties of embodiments 1 to 3 are significantly better than those of comparative example 3, indicating that the present invention selects ball-milled microsphere cellulose as a raw material and solvent A as a dissolving system to effectively improve the mechanical properties of the hydrogel. This may be because after being treated in a limited manner of the present invention, the cellulose can be highly dispersed in the reaction system and the reactivity is enhanced, thereby increasing the crosslinking density of the hydrogel.

[0035] Table 6 Mechanical properties test results of examples and comparative examples The above are only specific embodiments of the present invention, but the technical features of the present invention are not limited thereto. Any simple changes, equivalent replacements or modifications made based on the present invention to solve basically the same technical problems and achieve basically the same technical effects are all included in the protection scope of the present invention.

Claims

1. A molecular imprinting material for paclitaxel adsorption and a preparation method thereof, characterized in that: The preparation method of molecular imprinted material comprises the following steps: (1) Preparation of cellulose microspheres: After the prepared solution A is mixed evenly with dimethyl sulfoxide, microcrystalline cellulose is added and stirred at 95-105°C until completely dissolved. Sodium bicarbonate and epichlorohydrin are added at 22-28°C and stirred for 30-60 min. The mixture is transferred to a glass mold and allowed to stand at 8-12°C for 10-14 h for gelation. The obtained gel is then sieved through a 100-120 mesh sieve to prepare microspheres. The microspheres are then immersed in a 5 wt% hydrochloric acid solution and allowed to stand for 8-16 h. Finally, the microspheres are washed with deionized water for 3-5 times to obtain cellulose microspheres. (2) Preparation of modified cellulose microspheres: 20 wt% acetic acid aqueous solution, anhydrous ethanol, and 3-(methacryloyloxy)propyltrimethoxysilane (MPS) were mixed evenly and stirred at 55-65°C for 1-1.5 h, and then the cellulose microspheres prepared in step (1) were added, and the temperature was kept constant and stirred for 3-4 h. The solid was filtered and rinsed with deionized water for 3-5 times to obtain modified cellulose microspheres; (3) Preparation of molecular imprinting material: Paclitaxel, acrylamide (AM) and methanol were mixed evenly and stirred at 22-28°C in the dark for 12-14 h. The modified cellulose microspheres prepared in step (2), divinylbenzene (DVB), trimethylolpropane trimethacrylate (TMPTMA) and azobisisobutyronitrile (AIBN) were then added to the mixture, and the mixture was magnetically stirred at 60-70°C in the dark for 22-26 h under nitrogen protection. Finally, the solid was eluted with an eluent for 5-6 times to remove paclitaxel, and the solid was washed with methanol for 3-5 times to remove acetic acid, thereby obtaining a molecular imprinting material with specific adsorption effect on paclitaxel.

2. The method for preparing a molecularly imprinted material according to claim 1, characterized in that: The preparation method of solution A in step (1) is as follows: a strongly alkaline organic reagent and a carboxylic acid are uniformly mixed in a molar ratio of 2:1, stirred at 85-95° C. until a clear liquid is obtained, and then continued to stir for 3-4 hours.

3. The method for preparing a molecularly imprinted material according to claim 1, characterized in that: The microcrystalline cellulose in step (1) is ball-milled, and the ball-milling conditions are a ball-to-material ratio of 30:1, a rotation speed of 300-500 rpm / min, and a time of 5-6 hours.

4. The method for preparing a molecularly imprinted material according to claim 1, wherein: In step (1), the mass (g) of microcrystalline cellulose, sodium bicarbonate, dimethyl sulfoxide, solution A and the volume (mL) of epichlorohydrin are in the ratio of 1: (0.2-0.3): (7-10): (28-40): (0.45-0.55).

5. The method for preparing a molecularly imprinted material according to claim 1, characterized in that: In step (2), the volume ratio of acetic acid aqueous solution, anhydrous ethanol, and 3-(methacryloyloxy)propyltrimethoxysilane (MPS) is 1:(5-8):(0.24-0.28), and the ratio of the mass (g) of cellulose microspheres to the volume (mL) of 3-(methacryloyloxy)propyltrimethoxysilane (MPS) is 1:(1.2-1.5).

6. The method for preparing a molecularly imprinted material according to claim 1, characterized in that: In the reaction of step (3), the molar ratio of paclitaxel, acrylamide (AM), divinylbenzene (DVB), trimethylolpropane trimethacrylate (TMPTMA), and azobisisobutyronitrile (AIBN) is 1: (12-14): (28-32): (28-32): (1.8-2.2), and the ratio of the volume (mL) of methanol, the mass (mg) of modified cellulose microspheres, and the mass (mg) of acrylamide (AM) is 1: (17-20): (1-1.4).

7. The method for preparing a molecularly imprinted material according to claim 1, characterized in that: In step (3), the eluent is prepared from methanol and acetic acid, wherein the volume ratio of methanol to acetic acid is 9:

1.

8. The method for preparing a molecularly imprinted material according to claim 2, characterized in that: The strong alkaline organic reagent is one of 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and the carboxylic acid is one of citric acid, glutaric acid, and adipic acid.

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