CN116003482B - Paeoniflorin-6 ， Ternary solvent drying method of-O-benzenesulfonate - Google Patents
Paeoniflorin-6 ， Ternary solvent drying method of-O-benzenesulfonate Download PDFInfo
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Abstract
The invention provides a ternary solvent drying method of paeoniflorin-6' -O-benzenesulfonate, which comprises the following steps: will bePaeoniflorin-6' -O-benzenesulfonate is dissolved in the mixed solvent and subjected to programmed drying; the mixed solvent comprises dimethyl carbonate and C in a specific proportion 3～4 Ketones and water. The drying method can reduce the solvent residue of paeoniflorin-6 ' -O-benzenesulfonate, ensure that the solvent residue of paeoniflorin-6 ' -O-benzenesulfonate finished products is qualified, keep the stability of paeoniflorin-6 ' -O-benzenesulfonate, ensure that the content of related substances is not obviously increased, ensure the quality of paeoniflorin-6 ' -O-benzenesulfonate finished products, and be suitable for industrial production of paeoniflorin-6 ' -O-benzenesulfonate.
Description
Technical Field
The invention belongs to the technical field of compound post-treatment, and particularly relates to a ternary solvent drying method of paeoniflorin-6' -O-benzenesulfonate.
Background
The total glucosides of paeony (total glucosides of paeony, TGP) are glycoside active ingredients extracted from root parts of plant white paeony root, have various pharmacological activities such as immunoregulation, anti-inflammatory, liver protection, antipyresis and analgesia, have less adverse effects after long-term administration and no obvious toxic or side effects, and are widely applied to the treatment of rheumatic immune diseases. Paeoniforin (Pae) is the main active ingredient of TGP, and has remarkable pharmacological effects, but its lipophilicity is weak and oral absorption is poor, so that its clinical use is limited.
Thus, derivatization modifications to Pae may overcome the above disadvantages. Research shows that Pae reacts with benzenesulfonyl chloride to prepare paeoniflorin-6' -O-benzenesulfonate derivative which has higher anti-inflammatory activity and bioavailability and shows good pharmaceutical activity. However, paeoniflorin-6' -O-benzenesulfonate has the characteristics of strong lipophilicity, difficult crystallization, strong hygroscopicity, poor thermal stability and the like, and the difficulty of a drying process is obviously increased. After the precipitate is directly dried by adopting the prior art, the solvent wrapping phenomenon exists in the finished product, so that the solvent residue is seriously out of standard. If the sample is directly dried in vacuum after being dissolved, paeoniflorin-6' -O-benzenesulfonate is easy to degrade alcohol, so that related substances are obviously increased, and the research of a drying process is certainly challenged. The sublimation principle is utilized to carry out programmed heating and drying on the material under the low temperature and vacuum conditions, and the method is suitable for preparing the heat-sensitive material. Materials soluble and stable in aqueous solution may be subjected to this drying procedure using water as the only solvent, but paeoniflorin-6' -O-benzenesulfonate is not suitable because it is slightly soluble in water. Tertiary butanol with high melting point, high vapor pressure, non-toxic and water-miscible characteristics is an excellent choice of a drying solvent for poorly water-soluble and thermolabile drugs, and tertiary butanol-water cosolvent has been used in the production process of various injection drugs, can improve the drying efficiency and shorten the drying time, but paeoniflorin-6' -O-benzenesulfonate is unstable in alcohol-containing solvents and is easy to degrade, so that the quality of the finished product is greatly reduced and is not in accordance with the requirements.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems in the prior art described above. Therefore, the invention provides a drying method of paeoniflorin-6 '-O-benzenesulfonate, which can ensure that the solvent residue of paeoniflorin-6' -O-benzenesulfonate is qualified, and meanwhile, the content of related substances (related substances refer to impurities in the preparation process of paeoniflorin-6 '-O-benzenesulfonate) of a finished product cannot be increased, so that the drying method is suitable for industrial production of paeoniflorin-6' -O-benzenesulfonate.
In the existing drying process, if the precipitate of paeoniflorin-6' -O-benzenesulfonate is directly dried, the solvent wrapping phenomenon exists in the finished product, so that the solvent residue is seriously out of standard; if the sample is directly dried in vacuum after being dissolved, paeoniflorin-6' -O-benzenesulfonate is easy to degrade alcohol, so that related substances are obviously increased. By utilizing the principle of sublimation, the material solution is quickly frozen under the condition of relatively low temperature, then the material is heated under the proper vacuum environment, the frozen solvent molecules are directly sublimated into steam to overflow, and the material itself is remained in an ice frame during freezing, so that the program type drying method is suitable for preparing the material which is not resistant to high temperature.
Paeoniflorin-6' -O-benzenesulfonate is slightly soluble in water, and is not suitable for a program drying process using water as a solvent. The organic solvent can increase the solubility of materials which are difficult to dissolve in water and improve the drying efficiency, but the addition of the organic solvent also brings a certain risk to the quality of the product, for example, samples need to be kept stable in the organic solvent, the residual of the organic solvent in the finished product must be lower than a specified limit, and the toxicity, flammability and explosiveness of certain organic solvents need to be considered at the same time. Paeoniflorin-6' -O-benzenesulfonate is easily dissolved in certain alcohols, ketones, and carbonates. However, paeoniflorin-6' -O-benzenesulfonate is easy to be degraded in alcohol solvent and unstable, and the common tertiary butanol or tertiary butanol-water cosolvent mixed system meeting the requirements of melting point and vapor pressure is not applicable. After the paeoniflorin-6' -O-benzenesulfonate is subjected to the programmed drying by using a single ketone or carbonate solvent, the solvent residue is obviously out of limit, so that the quality of the finished product is unqualified. At the same time, the miscibility of the mixed solvent in a specific ratio also affects the quality of the finished product. Therefore, the organic solvent or the mixed solvent system with a specific proportion meeting the requirements of a program type drying process is screened, paeoniflorin-6 '-O-benzenesulfonate can be dissolved, the quality of a finished product is kept to meet the requirements, and the method is stable and controllable, and becomes the key of the paeoniflorin-6' -O-benzenesulfonate drying process.
Therefore, the invention provides a drying method of paeoniflorin-6' -O-benzenesulfonate, which comprises the following steps: dissolving paeoniflorin-6' -O-benzenesulfonate in a mixed solvent, and performing program drying; the mixed solvent comprises dimethyl carbonate and C 3～4 Ketones and water.
The invention provides the dimethyl carbonate and C in a certain proportion 3～4 The ketone and water ternary solvent system meets the requirement of a program type drying process solvent, successfully solves the problem of drying the fat-soluble paeoniflorin-6' -O-benzenesulfonate, and simultaneously ensures that the residual quantity of related substances and solvents of a finished product is lower than a specified value.
In some embodiments of the invention, the mixed solvent has a freezing point of-10 to 0 ℃.
In some embodiments of the invention, the C 3～4 The ketone comprises at least one of acetone and butanone.
In some embodiments of the invention, the mixed solvent consists of dimethyl carbonate, acetone and water, or consists of dimethyl carbonate, butanone and water. Under the combination, the mixed solvent has better solubility to paeoniflorin-6' -O-benzenesulfonate, thereby achieving better reduction of solvent residue and reduction of the increase of related substance content after the drying process.
In some embodiments of the invention, the dimethyl carbonate, C 3～4 The volume ratio of ketone to water is 4-11: 0.2 to 0.6:1, preferably 5 to 8:0.3 to 0.5:1.
alternatively, for convenience of practical operation, the composition of the mixed solution may be set as follows in percentage by volume: dimethyl carbonate: 71% -90%, C 3～4 Ketones: 2% -10% of water: 7-19% of dimethyl carbonate, C 3～4 The sum of the volume percentages of ketone and water is 100%.
In some embodiments of the present invention, the ratio of the mixed solvent to paeoniflorin-6' -O-benzenesulfonate is 1-20 mL:1g, more preferably 1 to 15mL:1g, more preferably 1 to 5mL:1g.
In some embodiments of the invention, the procedural drying comprises a prefreezing, sublimation drying, and analytical drying step in sequence; preferably, the temperatures of the prefreezing, sublimation drying and analytical drying are sequentially increased.
In some embodiments of the invention, the pre-frozen temperature is-60 to-10 ℃, preferably-40 to-10 ℃.
In some preferred embodiments of the invention, the pre-freezing step is to cool to-60 to-10 ℃ and keep the temperature for 30-300 min; preferably, the temperature is reduced to-40 to-10 ℃ and kept for 90-300 min.
In some embodiments of the invention, the sublimation drying temperature is between-10 and 0 ℃.
In some preferred embodiments of the present invention, the sublimation drying step is to raise the temperature to-10 to 0 ℃ within 30 to 180 minutes and keep the temperature for 180 to 720 minutes; preferably, the temperature is raised to-10 to 0 ℃ within 60 to 180min and kept for 240 to 600min.
In some embodiments of the present invention, the temperature of the resolution drying is 5 to 65 ℃, preferably the resolution drying includes the step of performing the resolution drying in two temperature ranges of 5 to 20 ℃ and 50 to 65 ℃ in sequence.
In some preferred embodiments of the invention, the analytical drying step is to heat up to 5-20 ℃ and hold for 60-600 min within 30-240 min, followed by heating up to 50-65 ℃ and hold for 300-1440 min within 30-240 min. More preferably, the analytical drying step is to heat up to 5-15 ℃ and keep the temperature for 90-540 min in 60-180 min, and then heat up to 50-60 ℃ and keep the temperature for 480-1440 min in 60-180 min.
In some embodiments of the present invention, the total solvent residue of paeoniflorin-6' -O-benzenesulfonate after the programmed drying is no more than 0.6%. Preferably, after the programmed drying, the carbonate residue of paeoniflorin-6' -O-benzenesulfonate is not higher than 0.5%, C 3～4 The ketone residue is not higher than 0.2%.
In some embodiments of the present invention, the content of related substances in paeoniflorin-6' -O-benzenesulfonate increases by not more than 0.2% after the program drying.
The beneficial effects of the invention are as follows:
according to the invention, through the ternary solvent system program drying process of paeoniflorin-6 '-O-benzenesulfonate, the content of related substances can be obviously reduced while the qualification of the solvent residue of a paeoniflorin-6' -O-benzenesulfonate finished product is ensured, the high quality of the paeoniflorin-6 '-O-benzenesulfonate finished product is ensured, and the method is suitable for industrial production of paeoniflorin-6' -O-benzenesulfonate.
Detailed Description
The conception and the technical effects produced by the present invention will be clearly and completely described in conjunction with the embodiments below to fully understand the objects, features and effects of the present invention. It is apparent that the described embodiments are only some embodiments of the present invention, but not all embodiments, and that other embodiments obtained by those skilled in the art without inventive effort are within the scope of the present invention based on the embodiments of the present invention.
Example 1
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (80 mL of dimethyl carbonate, 5mL of acetone and 15mL of water) was added, stirred to dissolve completely, and placed in a dish, and a drying procedure was performed according to the parameters of Table 1. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 1 example 1 drying parameters and sample quality inspection table
Example 2
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (80 mL of dimethyl carbonate, 5mL of butanone and 15mL of water) was added, stirred to dissolve completely, placed in a dish, and dried according to the parameters of Table 2. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 2 example 2 drying parameters and sample quality inspection table
Example 3
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (80 mL of dimethyl carbonate, 10mL of acetone and 10mL of water) was added, stirred to dissolve completely, and placed in a dish, and a drying procedure was performed according to the parameters of Table 3. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 3 example 3 drying parameters and sample quality inspection table
Example 4
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (48 mL of dimethyl carbonate, 3mL of acetone and 9mL of water) was added, stirred to dissolve completely, and placed in a dish, and a drying procedure was performed according to the parameters of Table 4. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 4 example 4 drying parameters and sample quality inspection table
Example 5
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (16 mL of dimethyl carbonate, 1mL of acetone and 3mL of water) was added, stirred to dissolve completely, and placed in a dish, and a drying procedure was performed according to the parameters of Table 5. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 5 example 5 drying parameters and sample quality inspection table
Example 6
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (240 mL of dimethyl carbonate, 15mL of acetone and 45mL of water) was added, stirred to dissolve completely, and placed in a dish, and a drying procedure was performed according to the parameters of Table 6. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
TABLE 6 example 6 drying parameters and sample quality inspection tables
Example 7
10kg of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (40L of dimethyl carbonate, 2.5L of acetone and 7.5L of water) was added, stirred to dissolve completely, placed in a dish, and dried according to the parameters of Table 7. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 7 example 7 drying parameters and sample quality inspection table
Example 8
10kg of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (40L of dimethyl carbonate, 2.5L of butanone and 7.5L of water) was added, stirred to dissolve completely, placed in a dish, and dried according to the parameters of Table 8. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 8 example 8 drying parameters and sample quality inspection table
Example 9
500kg of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (2000L of dimethyl carbonate, 125L of acetone and 375L of water) was added thereto, stirred to be completely dissolved, and placed in a dish, and a drying procedure was performed according to the parameters of Table 9. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 9 example 9 drying parameters and sample quality inspection table
Example 10
500kg of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (2000L of dimethyl carbonate, 125L of butanone and 375L of water) was added, stirred to be completely dissolved, placed in a dish, and dried according to the parameters of Table 10. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 10 example 10 drying parameters and sample quality inspection table
Comparative example 1
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, added with 20mL of methanol, stirred to be completely dissolved, and placed in a vacuum drying oven for vacuum drying according to the parameters shown in Table 11. After drying, samples were collected, sampled and inspected for solvent residues and related substances.
Table 11 comparative example 1 drying parameters and sample quality inspection table
Comparative example 2
20g of paeoniflorin-6' -O-benzenesulfonate is weighed, 20mL of acetone is added, the mixture is stirred to be completely dissolved, and the mixture is placed in a vacuum drying oven to be dried in vacuum according to the parameters shown in Table 12. After drying, samples were collected, sampled and inspected for solvent residues and related substances.
Table 12 comparative example 2 drying parameters and sample quality inspection table
Comparative example 3
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (80 mL of t-butanol+20 mL of water) was added thereto, stirred to be completely dissolved, and placed in a dish, and a drying procedure was performed according to the parameters of Table 13. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 13 comparative example 3 drying parameters and sample quality inspection table
Comparative example 4
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, added with a solvent (100 mL of dimethyl carbonate), stirred to dissolve completely, placed in a dish, and subjected to a drying procedure according to the parameters shown in Table 14. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 14 comparative example 4 drying parameters and sample quality inspection table
Comparative example 5
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, added with a solvent (100 mL diethyl carbonate), stirred to dissolve completely, placed in a dish, and subjected to a drying procedure according to the parameters shown in Table 15. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 15 comparative example 5 drying parameters and sample quality inspection table
Comparative example 6
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (85 mL of dimethyl carbonate and 15mL of acetone) was added thereto, stirred to be completely dissolved, and placed in a dish, and a drying procedure was performed according to the parameters of Table 16. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 16 comparative example 6 drying parameters and sample quality inspection tables
Comparative example 7
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (85 mL diethyl carbonate and 15mL acetone) was added thereto, stirred to be completely dissolved, and placed in a dish, and a drying procedure was performed according to the parameters of Table 17. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 17 comparative example 7 drying parameters and sample quality inspection table
Comparative example 8
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (85 mL of dimethyl carbonate and 15mL of cyclohexanone) was added thereto, stirred to be completely dissolved, placed in a dish, and subjected to a drying procedure according to the parameters of Table 18. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 18 comparative example 8 drying parameters and sample quality inspection table
Comparative example 9
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (80 mL diethyl carbonate, 5mL acetone and 15mL water) was added, stirred to dissolve completely, and placed in a dish, and a drying procedure was performed according to the parameters of Table 19. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 19 comparative example 9 drying parameters and sample quality inspection table
Comparative example 10
20g of paeoniflorin-6' -O-benzenesulfonate was weighed, mixed solvent (80 mL of dimethyl carbonate, 5mL of cyclohexanone and 15mL of water) was added, stirred to dissolve completely, placed in a dish, and dried according to the parameters shown in Table 20. After drying, the sample powder was collected, sampled and inspected for solvent residues and related substances.
Table 20 comparative example 10 drying parameters and sample quality inspection tables
The drying results of example 1 and example 2 and comparative examples 1 to 10 were compared together, as shown in the following table:
table 21 summary of results for example 1, example 2 and comparative example
In examples 1 and 2, compared with comparative examples 1 to 10, it was found that the solvent residue of paeoniflorin-6 '-O-benzenesulfonate was able to meet the standard, the related substances were not significantly increased, and the quality of the dried product was ensured by using dimethyl carbonate, acetone and water, or a combination of dimethyl carbonate, butanone and water as the solvent, and then performing the program drying after dissolving paeoniflorin-6' -O-benzenesulfonate. And methanol is used as a solvent, paeoniflorin-6' -O-benzenesulfonate is dried in vacuum, and the residual solvent can meet the standard, but related substances are obviously increased. And (3) using acetone as a solvent to carry out vacuum drying on paeoniflorin-6' -O-benzenesulfonate, wherein the solvent residue of the acetone cannot be reduced below the standard although related substances are not obviously increased. And tert-butanol-water is used as a solvent, paeoniflorin-6' -O-benzenesulfonate is subjected to programmed drying, the solvent residue accords with the standard, but related substances are obviously increased, and the quality of a dried finished product is obviously deteriorated. And only dimethyl carbonate or diethyl carbonate is used as a solvent, paeoniflorin-6' -O-benzenesulfonate is subjected to programmed drying, and the solvent residue of the dimethyl carbonate or diethyl carbonate cannot be reduced below the standard. Also, dimethyl carbonate and acetone, diethyl carbonate and acetone, or binary mixed solvent of dimethyl carbonate and cyclohexanone are used; or using ternary mixed solvent of diethyl carbonate, acetone and water, diethyl carbonate, cyclohexanone and water to carry out programmed drying on paeoniflorin-6' -O-benzenesulfonate, and the solvent residue can not be reduced below the standard. It can be seen that only the use of specific mixed solvents can meet the requirements that the solvent residue meets the standard and the related substances have no increase.
Comparative example 11
Weighing 20g of paeoniflorin-6' -O-benzenesulfonate, adding 100mL of mixed solvent of dimethyl carbonate, acetone and water according to a different proportion in accordance with a table 22, stirring to dissolve completely, performing program drying, collecting sample powder, sampling, and inspecting solvent residues and related substances.
TABLE 22 Mixed solvent State and sample quality inspection Table for different proportions
The mixed solvent consisting of dimethyl carbonate, acetone and water is used as a solvent for programmed drying, and a finished product with qualified quality can not be obtained in any proportion. And (3) carrying out the result investigation of the residual solvent of the finished product and related substances by setting mixed solvents in different proportions. Acetone in the mixed solvent: when the water ratio is less than 1:4, as shown in groups 1, 2 and 8 in the table, layering phenomenon occurs in the mixed system, and the dimethyl carbonate in the finished product exceeds the limit, so that the drying effect is affected; when the acetone content in the mixture system exceeds 10%, as shown in group 4, the acetone residue in the finished product exceeds the limit. When the volume ratio of the dimethyl carbonate to the acetone to the water is 4-11: 0.2 to 0.6: in the step 1, the mixed solvent system is not layered, the solvent residues of the dimethyl carbonate and the acetone meet the specified requirements, and the related substances are not obviously increased after drying. It can be seen that only dimethyl carbonate, C, is used in a specific ratio 3～4 The mixed solvent of ketone and water can reach the aim of meeting the standard of the residual solvent and having no increase of related substances. Therefore, the invention can solve the key problem of drying in paeoniflorin-6' -O-benzenesulfonate crude drug development, and lays an important foundation for the industrialized production thereof.
While the embodiments of the present invention have been described in detail, the present invention is not limited to the above embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art. Furthermore, embodiments of the invention and features of the embodiments may be combined with each other without conflict.
Claims (10)
1. A drying method of paeoniflorin-6' -O-benzenesulfonate is characterized by comprising the following steps: the method comprises the following steps: dissolving paeoniflorin-6' -O-benzenesulfonate in a mixed solvent, and performing program drying; the mixed solvent is prepared from dimethyl carbonate, C 3~4 Ketones and water;
the dimethyl carbonate, C 3~4 The volume ratio of ketone to water is 4-11: 0.2 to 0.6:1, a step of;
the C is 3~4 The ketone is acetone or butanone;
the program type drying sequentially comprises the steps of prefreezing, sublimation drying and analysis drying;
the pre-freezing step is that the temperature is reduced to minus 60 to minus 10 ℃ and the temperature is kept for 30 to 300 minutes;
the sublimation drying step comprises the steps of heating to-10-0 ℃ within 30-180 min and preserving heat for 180-720 min;
the analytical drying step comprises the steps of heating to 5-20 ℃ within 30-240 min, preserving heat for 60-600 min, heating to 50-65 ℃ within 30-240 min, and preserving heat for 300-1440 min.
2. The method for drying paeoniflorin-6' -O-benzenesulfonate according to claim 1, wherein the method comprises the steps of: the solidifying point of the mixed solvent is-10-0 ℃.
3. The drying method of paeoniflorin-6' -O-benzenesulfonate according to claim 1 or 2, wherein the method comprises the following steps: the dimethyl carbonate, C 3~4 The volume ratio of ketone to water is 5-8: 0.3 to 0.5:1.
4. the method for drying paeoniflorin-6' -O-benzenesulfonate according to claim 1, wherein the method comprises the steps of: the ratio of the mixed solvent to paeoniflorin-6' -O-benzenesulfonate is 1-20 mL:1g.
5. The method for drying paeoniflorin-6' -O-benzenesulfonate according to claim 1, wherein the method comprises the steps of: the ratio of the mixed solvent to paeoniflorin-6' -O-benzenesulfonate is 1-15 mL:1g.
6. The method for drying paeoniflorin-6' -O-benzenesulfonate according to claim 1, wherein the method comprises the steps of: the ratio of the mixed solvent to paeoniflorin-6' -O-benzenesulfonate is 1-5 mL:1g.
7. The method for drying paeoniflorin-6' -O-benzenesulfonate according to claim 1, wherein the method comprises the steps of: the temperatures of the prefreezing, sublimation drying and analytical drying are sequentially increased.
8. The method for drying paeoniflorin-6' -O-benzenesulfonate according to claim 1, wherein the method comprises the steps of: the pre-freezing step is to cool to-40 to-10 ℃ and keep the temperature for 90-300 min.
9. The method for drying paeoniflorin-6' -O-benzenesulfonate according to claim 1, wherein the method comprises the steps of: the sublimation drying step is that the temperature is raised to-10-0 ℃ within 60-180 min, and the temperature is kept for 240-600 min.
10. The method for drying paeoniflorin-6' -O-benzenesulfonate according to claim 1, wherein the method comprises the steps of: the analytical drying step comprises the steps of heating to 5-15 ℃ within 60-180 min, preserving heat for 90-540 min, heating to 50-60 ℃ within 60-180 min, and preserving heat for 480-1440 min.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202111234401.XA CN116003482B (en) | 2021-10-22 | 2021-10-22 | Paeoniflorin-6 ， Ternary solvent drying method of-O-benzenesulfonate |
| PCT/CN2021/129873 WO2023065422A1 (en) | 2021-10-22 | 2021-11-10 | Ternary solvent drying method for paeoniflorin-6'-o-benzene sulfonate |
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| CN202111234401.XA CN116003482B (en) | 2021-10-22 | 2021-10-22 | Paeoniflorin-6 ， Ternary solvent drying method of-O-benzenesulfonate |
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