A drying process capable of effectively reducing the amount of solvent residues in glycoproteins

Abstract

The application belongs to the technical field of medicine, and provides a drying process which can effectively reduce the residual amount of organic solvents in glycoprotein. The drying process which can effectively reduce the residual amount of organic solvents in glycoprotein can continuously and effectively remove the organic solvents by controlling the vacuum degree of the drying box at 10-60 mbar and the relative humidity at 50-90% during the drying process of the glycoprotein, so that the drying efficiency of the product is greatly improved, and the whole operation process no longer needs to replace the aqueous solution, thereby reducing the process operation difficulty; the mass percentage of the organic solvents in the glycoprotein drying product is not more than 0.1% or even lower, which greatly improves the drying efficiency of the target product, and the product stability is better.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology and provides a drying process that can effectively reduce the amount of residual organic solvents in glycoproteins. Background Technology

[0002] Glycoproteins used to treat infertility are a class of structurally similar substances, including human chorionic gonadotropin (HCG), menopausal gonadotropin (HMG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). HCG, FSH, and LH are all composed of α and β subunits linked by non-covalent bonds. Clinically, HCG, HMG, FSH, and LH are primarily used to treat infertility and for in-vitro assisted reproduction. They can be extracted from the urine of specific women (pregnant or menopausal) or prepared using recombinant gene technology.

[0003] However, glycoprotein raw materials used to treat infertility require an environment below -20°C for storage in liquid form; otherwise, the glycoproteins are easily deactivated, making liquid storage unsuitable. Furthermore, liquid glycoproteins are more prone to deactivation due to the freeze-thaw cycle, or even repeated freeze-thaw processes. Additionally, the packaging containers of liquid glycoproteins are susceptible to breakage at low temperatures, making them unsuitable for routine transportation. Therefore, solid glycoprotein products are more suitable for clinical applications and industrial transportation.

[0004] Currently, the main method for producing solid glycoprotein active pharmaceutical ingredients (APIs) is through freeze-drying and / or vacuum drying. The main challenges are the ease with which high-purity glycoproteins denature and become inactive during freeze-drying, and the unsatisfactory removal of organic solvents. Taking vacuum drying as an example, the process typically involves thoroughly mixing the organic solvent with the glycoprotein solution to form a precipitate, followed by dehydration, and then vacuum drying the precipitate. While this method can reduce glycoprotein denaturation and inactivation, the residual organic solvent content in the dried glycoprotein is high, sometimes exceeding 1%, thus affecting the product's application efficacy.

[0005] For example, Chinese patent CN102743742A discloses a vacuum drying method for a glycoprotein composition with low solvent residue. This method involves thoroughly mixing an organic solvent with a solution containing the glycoprotein raw material to precipitate the precipitate, collecting the precipitate, and then vacuum drying it together with a water system. This effectively controls the organic solvent content to below 0.5%. However, in practical applications, it has been found that this process requires frequent changes of the aqueous solution, increasing operational difficulty and resulting in lower drying efficiency. Furthermore, there is still a desire to further reduce the residual solvent content in the glycoprotein to obtain a higher quality product.

[0006] Therefore, there is an urgent need in this field to develop a simple and effective vacuum drying method to reduce the residual organic solvents in glycoproteins. Summary of the Invention

[0007] Therefore, the technical problem to be solved by the present invention is to provide a drying process that can effectively reduce the residual amount of organic solvent in glycoproteins. The method has the advantages of simple operation, higher drying efficiency and lower solvent residue in glycoprotein products.

[0008] The second technical problem to be solved by the present invention is to provide a glycoprotein with a lower organic solvent residue.

[0009] To solve the above-mentioned technical problems, the present invention provides a drying process that can effectively reduce the residual solvent content in glycoproteins, comprising the following steps:

[0010] (1) Take the raw material containing glycoprotein and mix it with an organic solvent, and collect the precipitate;

[0011] (2) The precipitate is vacuum dried in the presence of a water system under a vacuum of 10-60 mbar.

[0012] (3) Remove the water system and adjust the system vacuum to above 0.1 mbar to continue vacuum drying treatment to obtain the product.

[0013] Specifically, in step (1), the organic solvent includes ethanol;

[0014] Preferably, the organic solvent includes ethanol with a mass concentration greater than 95 wt%.

[0015] Specifically, in step (1), the amount of organic solvent added is at least four times the volume of the raw material containing glycoprotein.

[0016] Specifically, step (1) further includes a step of dehydrating the precipitate with the organic solvent.

[0017] Specifically, the amount of organic solvent added is at least 20 times the weight of the precipitate.

[0018] Specifically, in step (2), the vacuum degree of the vacuum drying step is 30-50 mbar.

[0019] Specifically, in step (2), the temperature of the vacuum drying step is 10-25℃.

[0020] Specifically, in step (2), the relative humidity of the vacuum drying step is 50-90%, preferably 60-80%.

[0021] Specifically, in step (2), the drying time of the vacuum drying step is 4-24 hours.

[0022] Specifically, in step (3), the vacuum degree of the vacuum drying step is 0.001-0.01 mbar;

[0023] Preferably, the vacuum degree of the vacuum drying step is 0.02-0.06 mbar.

[0024] Specifically, in step (3), the temperature of the vacuum drying step is 10-25℃.

[0025] Specifically, in step (3), the vacuum drying step takes 4-24 hours.

[0026] Specifically, the water system includes substances that can generate water vapor;

[0027] Preferably, in the water system, the substances that can generate water vapor include water in liquid, solid, gaseous, or mixed forms.

[0028] Specifically, the water system includes an aqueous solution;

[0029] Preferably, the water in the aqueous solution includes at least one of tap water, deionized water, reverse osmosis water, pure water, or water for injection.

[0030] In the method for obtaining glycoprotein samples with low solvent residue provided by the present invention, the "vacuum drying of the glycoprotein-containing precipitate together with the water system" refers to placing the precipitate containing the glycoprotein composition in the place where the sample is usually placed in the vacuum dryer, and placing an open container containing a substance that can release water vapor around (e.g., at the bottom) the vacuum dryer.

[0031] In the method for obtaining a glycoprotein composition with low solvent residue provided by the present invention, the "removal of water system" refers to moving an open container containing a substance that can release water vapor outside of a vacuum-drying environment.

[0032] The present invention also discloses a glycoprotein product with low solvent residue obtained by the drying process described above.

[0033] The drying process described in this invention, which effectively reduces the residual organic solvent content in glycoproteins, is based on in-depth research of a previously developed process that involves vacuum drying of glycoprotein-containing materials with a water system. During this research, it was discovered that without strict control of the vacuum level during the co-vacuum drying of glycoproteins and a water system, the relative humidity inside the drying chamber can be low. Furthermore, if the vacuum level exceeds a certain critical value, the aqueous solution may rapidly freeze, leading to a significant decrease in relative humidity within the drying chamber. Consequently, the water content of the product decreases further, and the organic solvent content stops decreasing, requiring frequent replacement of the aqueous solution to ensure continuous water vapor release and system stability, thus increasing the workload. Therefore, this invention, by controlling the vacuum level in the drying chamber at 10-60 mbar and the relative humidity at 50-90% during the glycoprotein drying process, can continuously and effectively remove organic solvents, significantly improving the drying efficiency of the product. The entire operation no longer requires replacement of the aqueous solution, reducing the complexity of the process. The organic solvent content in the dried glycoprotein product is no more than 0.1% by mass or even lower, greatly improving the drying efficiency of the target product and resulting in superior product stability. Attached Figure Description

[0034] To make the content of this invention easier to understand, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings, wherein...

[0035] Figure 1 The GC chromatogram is for a reference standard with an ethanol content of 0.5%.

[0036] Figure 2 The GC spectrum of the ethanol content in the HMG sample prepared in Example 1;

[0037] Figure 3 The GC spectrum of the ethanol content in the HMG sample prepared in Example 6;

[0038] Figure 4 The GC spectrum shows the ethanol content in the HMG sample prepared in Comparative Example 1. Detailed Implementation

[0039] In the following embodiments and comparative examples of the present invention, the residual amount of organic solvent in the obtained HMG samples was determined by GC method. The specific GC detection method is as follows:

[0040] Chromatographic column: HP-INNOWAX polyethylene glycol capillary (size: 30m × 0.53mm × 1μm);

[0041] Inlet temperature: 200℃;

[0042] Furnace temperature: Maintain at 60℃ for 5 minutes, then increase to 200℃ at a rate of 50℃ per minute and maintain for 15 minutes;

[0043] Detector temperature: 250℃;

[0044] Carrier gas: High-purity nitrogen;

[0045] Flow split ratio: 7:1;

[0046] Detector hydrogen flow rate: 30 ml / min;

[0047] Airflow rate: 400 ml / min;

[0048] Purging air flow rate: 25 ml / min;

[0049] Headspace sampler conditions include:

[0050] Heating equilibrium temperature: 90℃;

[0051] Metering loop temperature: 100℃;

[0052] Transmission line temperature: 110℃;

[0053] Equilibrium time: 20 min;

[0054] Injection time: 1 min;

[0055] Injection volume: 1 ml;

[0056] GC cycle time: 32 min.

[0057] Under the above detection conditions, the GC chromatogram of the glycoprotein standard with an ethanol content of 0.5% is attached. Figure 1 As shown in Table 1, the retention time, peak area, and detection mass content of the solvent are as follows.

[0058] Table 1. GC detection results of the reference standard with 0.5% ethanol content.

[0059] 1.735 690.6 0.5 ethanol

[0060] Example 1

[0061] Take 2 L of HMG solution (provided by Shanghai Tianwei Biopharmaceutical Co., Ltd.), add 8 L of anhydrous ethanol and mix thoroughly until no more precipitate forms. Filter and collect 30.2 g of precipitate. Add 650 ml of ethanol to the precipitate for dehydration to obtain wet HMG precipitate.

[0062] The above-mentioned HMG wet precipitate was subjected to vacuum drying together with a water system containing purified water. The system temperature was controlled at 10°C, the vacuum degree at 30 mbar, and the relative humidity at 80%. The water tray was not replaced during the drying process, and the vacuum drying was carried out for 8 hours.

[0063] At this point, the water system is removed, the temperature is controlled at 10°C, the vacuum degree is 0.02 mbar, and drying continues for 5 hours to obtain the HMG sample.

[0064] The residual organic solvent in the obtained HMG sample was detected using the aforementioned GC method. The GC chromatogram of the ethanol content in the HMG sample in this embodiment is attached. Figure 2 As shown in Table 2, the retention time, peak area, and detection mass content of the solvent are as follows.

[0065] Table 2. GC detection results of HMG samples in Example 1

[0066] 1.738 81.8 0.06 ethanol

[0067] In summary, the organic solvent content in the HMG sample obtained in this embodiment is 0.06%.

[0068] Example 2

[0069] Take 2 L of HMG solution (provided by Shanghai Tianwei Biopharmaceutical Co., Ltd.), add 8 L of anhydrous ethanol and mix thoroughly until no more precipitate forms. Filter and collect 31.6 g of the precipitate. Add 900 ml of ethanol to the precipitate for dehydration to obtain wet HMG precipitate.

[0070] The above-mentioned HMG wet precipitate was subjected to vacuum drying together with a water system containing purified water. The system temperature was controlled at 25°C, the vacuum degree at 50 mbar, and the relative humidity at 70%. The water tray was not replaced during the drying process, and the vacuum drying was carried out for 12 hours.

[0071] At this point, the water system is removed, the temperature is controlled at 10°C, the vacuum degree is 0.04 mbar, and drying continues for 8 hours to obtain the HMG sample.

[0072] The residual organic solvent content in the obtained HMG sample was detected using the aforementioned GC method. In this embodiment, the solvent content in the HMG sample was 0.04%.

[0073] Example 3

[0074] Take 2 L of HMG solution (provided by Shanghai Tianwei Biopharmaceutical Co., Ltd.), add 8 L of anhydrous ethanol and mix thoroughly until no more precipitate forms. Filter and collect 29.8 g of the precipitate. Add 800 ml of ethanol to the precipitate for dehydration to obtain wet HMG precipitate.

[0075] The above-mentioned HMG wet precipitate was subjected to vacuum drying together with a water system containing purified water. The system temperature was controlled at 20°C, the vacuum degree at 60 mbar, and the relative humidity at 90%. The water tray was not replaced during the drying process, and the vacuum drying was carried out for 6 hours.

[0076] At this point, the water system is removed, the temperature is controlled at 10°C, the vacuum degree is 0.05 mbar, and drying continues for 10 hours to obtain the HMG sample.

[0077] The residual organic solvent content in the obtained HMG sample was detected using the aforementioned GC method. In this embodiment, the solvent content in the HMG sample was 0.04%.

[0078] Example 4

[0079] Take 2 L of HMG solution (provided by Shanghai Tianwei Biopharmaceutical Co., Ltd.), add 8 L of 95% ethanol and mix thoroughly until no more precipitate forms. Filter and collect 31.4 g of precipitate. Add 1000 ml of ethanol to the precipitate for dehydration to obtain wet HMG precipitate.

[0080] The above-mentioned HMG wet precipitate was subjected to vacuum drying together with a water system containing purified water. The system temperature was controlled at 15°C, the vacuum degree at 20 mbar, and the relative humidity at 60%. The water tray was not replaced during the drying process, and the vacuum drying was carried out for 12 hours.

[0081] At this point, the water system is removed, the temperature is controlled at 10°C, the vacuum degree is 0.06 mbar, and drying continues for 6 hours to obtain the HMG sample.

[0082] The residual organic solvent content in the obtained HMG sample was detected using the aforementioned GC method. In this embodiment, the solvent content in the HMG sample was 0.12%.

[0083] Example 5

[0084] Take 2 L of HMG solution (provided by Shanghai Tianwei Biopharmaceutical Co., Ltd.), add 8 L of ethanol (98%) and mix thoroughly until no more precipitate forms. Filter and collect 29.6 g of precipitate. Add 800 ml of ethanol to the precipitate for dehydration to obtain wet HMG precipitate.

[0085] The above-mentioned HMG wet precipitate was subjected to vacuum drying together with a water system containing purified water. The system temperature was controlled at 20°C, the vacuum degree at 40 mbar, and the relative humidity at 80%. The water tray was not replaced during the drying process, and the vacuum drying was carried out for 10 hours.

[0086] At this point, the water system is removed, the temperature is controlled at 10°C, the vacuum degree is 0.04 mbar, and drying continues for 8 hours to obtain the HMG sample.

[0087] The residual organic solvent content in the obtained HMG sample was detected using the aforementioned GC method. In this embodiment, the solvent content in the HMG sample was 0.10%.

[0088] Example 6

[0089] Take 2 L of HMG solution (provided by Shanghai Tianwei Biopharmaceutical Co., Ltd.), add 8 L of anhydrous ethanol and mix thoroughly until no more precipitate forms. Filter and collect 33.4 g of precipitate. Add 1000 ml of ethanol to the precipitate for dehydration to obtain wet HMG precipitate.

[0090] The above-mentioned HMG wet precipitate was subjected to vacuum drying together with a water system containing purified water. The system temperature was controlled at 25°C, the vacuum degree at 50 mbar, and the relative humidity at 80%. The water tray was not replaced during the drying process, and the vacuum drying was carried out for 8 hours.

[0091] At this point, the water system is removed, the temperature is controlled at 10°C, the vacuum degree is 0.04 mbar, and drying continues for 10 hours to obtain the HMG sample.

[0092] The residual organic solvent in the obtained HMG sample was detected using the aforementioned GC method. The GC chromatogram of the ethanol content in the HMG sample in this embodiment is attached. Figure 3 As shown in Table 3, the retention time, peak area, and detection mass content of the solvent are as follows.

[0093] Table 3. GC detection results of HMG samples in Example 6

[0094] 1.743 58.3 0.04 ethanol

[0095] In summary, the organic solvent content in the HMG sample obtained in this embodiment is 0.04%.

[0096] Comparative Example 1

[0097] This comparative example follows the drying method described in Example 5 of Chinese Patent CN102743742B.

[0098] The HMG wet precipitate, which has been precipitated and dehydrated by ethanol, was subjected to vacuum drying together with a water system containing purified water. The system temperature was controlled at 0°C, the vacuum degree at 0.5 mbar, and the relative humidity at 10.2%. The water tray was not replaced during the drying process, and the vacuum drying was carried out for 24 hours.

[0099] At this point, the water system is removed, the temperature is controlled at 0°C, the vacuum degree is controlled at 0.05 mbar, and drying continues for 5 hours to obtain the HMG sample.

[0100] The residual organic solvent in the obtained HMG sample was determined using the aforementioned GC method. The GC chromatogram of the ethanol content in the comparative HMG sample is attached. Figure 4 As shown in Table 4, the retention time, peak area, and detection mass content of the solvent are as follows.

[0101] Table 4 shows the GC detection results of the HMG sample in Comparative Example 1.

[0102] 1.735 1137.7 0.82 ethanol

[0103] In summary, the organic solvent content in the HMG sample obtained in this comparative example is 0.82%.

[0104] Comparative Example 2

[0105] This comparative example follows the drying method described in Example 5 of Chinese Patent CN102743742B.

[0106] The HMG wet precipitate, which has been precipitated and dehydrated by ethanol, was subjected to vacuum drying together with a water system containing purified water. The system temperature was controlled at 0°C, the vacuum degree at 0.5 mbar, and the relative humidity at 10.6%. The purified water was replaced every 2 hours, and the vacuum drying was carried out for 24 hours.

[0107] At this point, the water system is removed, the temperature is controlled at 0°C, the vacuum degree is controlled at 0.05 mbar, and drying continues for 5 hours to obtain the HMG sample.

[0108] The residual organic solvent content in the obtained HMG sample was detected using the aforementioned GC method. The solvent content in the HMG sample obtained in this comparative example was 0.25%.

[0109] Comparative Example 3

[0110] The drying method for the HMG sample described in this comparative example is the same as that in Example 1, except that in step (2), the vacuum degree of the vacuum drying process is controlled to be 80 mbar.

[0111] The residual organic solvent content in the obtained HMG sample was detected by the aforementioned GC method. The solvent content in the HMG sample obtained in this comparative example was 0.96%.

[0112] Comparative Example 4

[0113] The drying method for the HMG sample described in this comparative example is the same as that in Example 1, except that the vacuum degree of the vacuum drying steps in steps (2) and (3) is the same.

[0114] The residual organic solvent content in the obtained HMG sample was detected by the aforementioned GC method. The solvent content in the HMG sample obtained in this comparative example was 1.56%.

[0115] As can be seen, the present invention, by selecting suitable vacuum and relative humidity conditions, and especially by controlling the operation of the two-step vacuum drying process at different vacuum values, effectively ensures the removal of solvents in glycoprotein products compared to traditional vacuum control methods. This effectively reduces the amount of residual solvents in glycoprotein products and ensures the stability and quality of the products.

[0116] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A drying method that can effectively reduce the amount of residual solvent in glycoproteins, characterized in that, Includes the following steps: (1) Take the raw material containing glycoprotein and mix it with an organic solvent, and collect the precipitate; (2) The precipitate is vacuum dried in the presence of a water system under a vacuum of 30-60 mbar. (3) Remove the water system and adjust the vacuum degree of the system to 0.02-0.05 mbar to continue vacuum drying treatment to obtain the product; In step (2), the relative humidity of the vacuum drying step is 70-90%; In step (1), the organic solvent is anhydrous ethanol; In step (1), the amount of organic solvent added is at least 4 times the volume of the raw material containing glycoprotein. Step (1) further includes a step of dehydrating the precipitate with the organic solvent, wherein the amount of organic solvent added is at least 20 times the weight of the precipitate. In step (2), the temperature of the vacuum drying step is 10-25℃; In step (2), the drying time of the vacuum drying step is 6-12 hours; In step (3), the temperature of the vacuum drying step is 10°C; In step (3), the vacuum drying step takes 5-10 hours.

2. The drying method according to claim 1, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, The amount of organic solvent added is at least 21.5-29.9 times the weight of the precipitate.

3. The drying method according to any one of claims 1-2, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, In step (2), the vacuum degree of the vacuum drying step is 50-60 mbar; In step (2), the temperature of the vacuum drying step is 20-25℃; In step (3), the vacuum degree of the vacuum drying step is 0.04-0.05 mbar; In step (3), the vacuum drying step takes 8-10 hours.

4. The drying method according to claim 1, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, In step (1), the amount of organic solvent added is 4 times the volume of the raw material containing glycoprotein. Step (1) further includes a step of dehydrating the precipitate with the organic solvent, wherein the amount of organic solvent added is 21.5 times the weight of the precipitate. In step (2), the vacuum degree of the vacuum drying step is 30 mbar; In step (2), the relative humidity of the vacuum drying step is 80%; In step (2), the temperature of the vacuum drying step is 10°C; In step (2), the drying time of the vacuum drying step is 8 hours; In step (3), the vacuum degree of the vacuum drying step is 0.02 mbar; In step (3), the vacuum drying step takes 5 hours.

5. The drying method according to claim 1, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, In step (1), the amount of organic solvent added is 4 times the volume of the raw material containing glycoprotein. Step (1) further includes a step of dehydrating the precipitate with the organic solvent, wherein the amount of organic solvent added is 28.5 times the weight of the precipitate. In step (2), the vacuum degree of the vacuum drying step is 50 mbar; In step (2), the relative humidity of the vacuum drying step is 70%; In step (2), the temperature of the vacuum drying step is 25°C; In step (2), the drying time of the vacuum drying step is 12 hours; In step (3), the vacuum degree of the vacuum drying step is 0.04 mbar; In step (3), the vacuum drying step takes 8 hours.

6. The drying method according to claim 1, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, The amount of organic solvent added is four times the volume of the raw material containing glycoprotein; Step (1) further includes a step of dehydrating the precipitate with the organic solvent, wherein the amount of organic solvent added is 26.8 times the weight of the precipitate. In step (2), the vacuum degree of the vacuum drying step is 60 mbar; In step (2), the relative humidity of the vacuum drying step is 90%; In step (2), the temperature of the vacuum drying step is 20°C; In step (2), the drying time of the vacuum drying step is 6 hours; In step (3), the vacuum degree of the vacuum drying step is 0.05 mbar; In step (3), the vacuum drying step takes 10 hours.

7. The drying method according to claim 1, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, The amount of organic solvent added is four times the volume of the raw material containing glycoprotein; Step (1) further includes a step of dehydrating the precipitate with the organic solvent, wherein the amount of organic solvent added is 29.9 times the weight of the precipitate. In step (2), the vacuum degree of the vacuum drying step is 50 mbar; In step (2), the relative humidity of the vacuum drying step is 80%; In step (2), the temperature of the vacuum drying step is 25°C; In step (2), the drying time of the vacuum drying step is 8 hours; In step (3), the vacuum degree of the vacuum drying step is 0.04 mbar; In step (3), the vacuum drying step takes 10 hours.

8. The drying method according to any one of claims 1-2 and 4-7, which can effectively reduce the amount of solvent residue in glycoproteins, is characterized in that, The water system includes substances that can generate water vapor.

9. The drying method according to claim 3, which can effectively reduce the amount of solvent residue in glycoproteins, is characterized in that, The water system includes substances that can generate water vapor.

10. The drying method according to claim 8, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, In the water system, substances that can generate water vapor include water in liquid, solid, gaseous, or mixed forms.

11. The drying method according to claim 9, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, In the water system, substances that can generate water vapor include water in liquid, solid, gaseous, or mixed forms.

12. The drying method according to claim 8, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, The water system includes an aqueous solution.

13. The drying method according to any one of claims 9-11, which can effectively reduce the amount of solvent residue in glycoproteins, is characterized in that, The water system includes an aqueous solution.

14. The drying method according to claim 12, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, The water in the aqueous solution includes at least one of tap water, deionized water, reverse osmosis water, pure water, or water for injection.

15. The drying method according to claim 13, which effectively reduces the amount of solvent residue in glycoproteins, is characterized in that, The water in the aqueous solution includes at least one of tap water, deionized water, reverse osmosis water, pure water, or water for injection.

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