A method for purifying avermectin and removing RRT0.49 impurities and avermectin
By using a combination technology of toluene solvent and composite detergent during the purification of avermectin, the content of RRT0.49 impurities in avermectin products was successfully reduced, and the content and yield of avermectin B1a was increased, solving the problem that impurities affect product performance.
Patent Information
- Application Number
- CN202211403355.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2022-11-10
- Publication Date
- 2025-02-28
- Estimated Expiration
- 2042-11-10
AI Technical Summary
The content of RRT0.49 impurities in avermectin products is high, affecting the performance of downstream products.
A method of purifying the impurities of RRT 0.49 is adopted, including mixing the avermectin paste with toluene vehicle and composite detergent (a mixture of water and ethanol), and reducing the content of RRT 0.49 is reduced by distillation and crystallization.
Effectively reduce the content of RRT 0.49 impurities in abalectin products to <0.3%, increase the content of abalectin B1a to >90%, and improve the yield of abalectin.
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Abstract
Description
Technical Field
[0001] The present application relates to the technical field of avermectin purification, and more specifically, to a method for purifying avermectin and removing RRT0.49 impurities, and avermectin. Background Art
[0002] Avermectin is a macrolide antibiotic with a 16-membered ring structure. It has excellent insecticidal and acaricidal effects, and also has the advantages of high efficiency, broad spectrum, easy degradation, and safety for humans and animals, and has received widespread attention and application. Avermectin mainly has 8 components, namely A1a, A1b, A2a, A2b, B1a, B1b, B2a, and B2b. At present, the main components of commercially available avermectin products are avermectin B1a and avermectin B1b, with the content of avermectin B1a being about 85% and that of avermectin B1b being about 2%, and it is generally calibrated with the content of avermectin B1a.
[0003] The production of avermectin products mainly involves three-stage fermentation, plate and frame filtration, flash drying, adding ethanol to form an ethanol extract, and concentrating to remove ethanol to obtain an avermectin paste. After that, toluene is used for dissolution, water is used for sugar removal, and toluene is concentrated to remove toluene to obtain a purified paste, and then ethanol is dissolved and crystallized to obtain an avermectin product. In the actual production process of avermectin products, the applicant uses a high-performance liquid chromatograph to detect the content of avermectin B1a in the avermectin product. Prepare the sample to be tested, then pass the sample to be tested into the high-performance liquid chromatograph, and calculate the content of avermectin B1a by the area normalization method. In the detection of the content of avermectin B1a, it was found that an obvious impurity peak appeared at RRT0.49, and the content of RRT0.49 impurities in the avermectin product was 0.54%. The content of RRT0.49 impurities is relatively high, which has a certain impact on the downstream products of avermectin, such as avermectin derivatives ivermectin and avermectin. Summary of the invention
[0004] In order to reduce the content of RRT0.49 impurities in avermectin, the present application provides a method for purifying avermectin and removing RRT0.49 impurities and avermectin.
[0005] In the first aspect, the present application provides a method for purifying avermectin and removing RRT0.49 impurities, using the following technical solution:
[0006] A method for purifying avermectin and removing RRT0.49 impurities comprises the following steps:
[0007] S1. Add avermectin paste to toluene solvent, heat to 70-75° C., stir to dissolve, then add composite detergent, keep warm and stir for 1-3 hours, keep warm and stand until stratification, separate while hot to obtain upper liquid and lower liquid;
[0008] S2, distilling the upper liquid under reduced pressure to obtain a purified paste;
[0009] S3, adding ethanol solvent to the purified paste, heating to 70-75° C., stirring to dissolve, cooling to crystallize, filtering, drying, and obtaining an avermectin product;
[0010] The composite detergent is a mixture of water and ethanol, and the weight ratio of the toluene solvent, water and ethanol is 10:(1-4):(0.4-0.6).
[0011] The method for purifying avermectin and removing RRT0.49 impurities of the present application makes the RRT0.49 impurity content in the avermectin product less than 0.3% through the mutual coordination between the steps, effectively reduces the impurities in the avermectin product, and reduces the influence of the RRT0.49 impurity on the performance of the avermectin product. In addition, the avermectin product maintains a relatively high avermectin B1a content, and the avermectin B1a content is greater than 90%.
[0012] In step S1, avermectin is first dissolved in a toluene solvent, and then a mixture of water and ethanol is added, and after standing and stratification, an upper layer liquid and a lower layer liquid are obtained. The upper layer liquid mainly contains toluene and avermectin, and the lower layer liquid mainly contains water, ethanol, and impurities. After separation, the lower layer liquid is discarded, and the impurities in the avermectin paste can be effectively removed. At the same time, during the stirring process of toluene and water, due to the presence of a certain interfacial tension between the two, it is impossible for water and the avermectin paste to be fully in contact, and a small amount of ethanol is added to the water, that is, the composite detergent of the present application is used, ethanol can not only maintain the normal subsequent stratification of the toluene solvent and water, but also reduce the interfacial tension between toluene and water, increase the contact between the avermectin paste and water, promote the dissolution of water-soluble impurities, and also dissolve the impurities soluble in ethanol and enter the lower layer of liquid, that is, by adding a small amount of ethanol, the dissolution of RRT0.49 impurities is promoted, the RRT0.49 impurity content in the avermectin product is reduced, and the content of avermectin B1a is increased.
[0013] Optionally, the weight ratio of the toluene solvent, water and ethanol is 10:1.5:0.5.
[0014] Since avermectin B1a is soluble in ethanol, adding a small amount of ethanol to the composite detergent reduces the content of RRT0.49 impurities in the avermectin output, but inevitably reduces the avermectin yield. The weight ratio of toluene solvent, water and ethanol is optimized to make the avermectin product have a lower RRT0.49 impurity content and a good avermectin yield, showing better comprehensive performance.
[0015] Optionally, in step S1, after adding the composite detergent and stirring for 1-3 hours, the open-pore sodium chloride particles are added, and the weight ratio of the toluene solvent to the open-pore sodium chloride particles is 10:(0.1-0.2);
[0016] Specifically, add compound detergent, keep warm and stir for 1-3 hours, add open-pore sodium chloride particles, continue to keep warm and stir for 20-40 minutes, and keep warm and stand until stratification.
[0017] In one embodiment, the weight ratio of toluene solvent and open-pore sodium chloride particles is 10:0.15. The weight ratio of toluene solvent and open-pore sodium chloride particles can also be set to 10:0.1, 10:0.2, etc. as needed.
[0018] By adopting the above technical scheme, perforated sodium chloride particles are added in toluene, and there are pores in the perforated sodium chloride particles, which can adsorb the impurities in the avermectin paste. And because the perforated sodium chloride particles are granular, the interface of toluene and water can also be destroyed, the contact of toluene and composite detergent is increased, and the dissolution of impurities is promoted. Simultaneously, based on the perforated sodium chloride particles being soluble in water, the perforated sodium chloride is dispersed in the composite detergent together with the impurities adsorbed therein, not only improving the impurity removal effect, but also increasing the surface tension of water, being convenient for composite detergent and toluene to be layered, and improving the avermectin yield. That is, in the present application, by adding perforated sodium chloride particles, the dissolution of impurities is further promoted, the RRT0.49 impurity content in the avermectin product is reduced, and the content of avermectin B1a and the avermectin yield are improved.
[0019] Optionally, the average particle size of the open-pored sodium chloride particles is 3-7 mm.
[0020] In one embodiment, the average particle size of the perforated sodium chloride particles is 5 mm. The average particle size of the perforated sodium chloride particles can also be set to 3 mm, 4 mm, 6 mm, 7 mm, etc. as needed.
[0021] When the particle size of the sodium chloride particles to be perforated is too small, the interface between toluene and water cannot be destroyed; when the particle size of the sodium chloride particles to be perforated is too large, the dissolution time of the perforated sodium chloride particles is reduced. When the particle size of the perforated sodium chloride particles is optimized and the average particle size is 3-7 mm, the perforated sodium chloride particles can show good use effects.
[0022] Optionally, the open-pore sodium chloride particles are prepared by the following method:
[0023] Sa. Stir and mix the sodium chloride coarse powder, sodium chloride fine powder and polyvinyl alcohol to obtain a mixture;
[0024] Sb, spray saturated sodium chloride aqueous solution into the mixture under continuous stirring, stir evenly, and then press and form at a pressure of 10-15t to obtain a primary finished product;
[0025] Sc, at a temperature of 80-90°C, heat preservation for 20-40 minutes, heat to 110-120°C, heat preservation for 50-70 minutes, heat to 850-900°C, heat preservation for 3-5 hours, cool down, and obtain open-pore sodium chloride particles;
[0026] The particle size of the sodium chloride coarse powder is 50-100 μm in continuous grading, the particle size of the sodium chloride fine powder is 1-50 μm in continuous grading, and the weight ratio of the sodium chloride coarse powder, the sodium chloride fine powder, the polyvinyl alcohol and the saturated sodium chloride aqueous solution is (65-75):(25-35):(0.5-1.5):(4-6).
[0027] In one embodiment, the weight ratio of sodium chloride coarse powder, sodium chloride fine powder, polyvinyl alcohol, and saturated sodium chloride aqueous solution is 70:30:1:5. The weight ratio of sodium chloride coarse powder, sodium chloride fine powder, polyvinyl alcohol, and saturated sodium chloride aqueous solution can also be set to 65:35:0.5:4, 65:35:1.5:6, 75:25:0.5:4, 75:25:1.5:6, etc. as needed.
[0028] By adopting the above technical scheme, with sodium chloride coarse powder as main ingredient, cooperate sodium chloride fine powder, through the composite between the two, increase the pore of perforated sodium chloride particles. And add polyvinyl alcohol, not only increase the bonding strength of raw materials, in high temperature treatment, polyvinyl alcohol can fully burn to form gas, play the role of pore making. Meanwhile, sodium chloride saturated aqueous solution is adopted in the present application, not only play the role of bonding, also reduce the dissolution of sodium chloride coarse powder, sodium chloride fine powder, in high temperature treatment, the water in sodium chloride saturated solution evaporates, and the sodium chloride separated out plays the role of bridging, increases the strength of perforated sodium chloride particles, and also improves the use effect of perforated sodium chloride particles.
[0029] Optionally, the content of avermectin B1a in the avermectin paste is 30-40%, and / or, the amount of the toluene solvent used is 5-15 times the weight of the avermectin paste, and / or,
[0030] The usage amount of the ethanol solvent is 2-3 times of the weight of the avermectin paste.
[0031] In one embodiment, the usage amount of toluene solvent is 10 times the weight of the avermectin paste, and the usage amount of toluene solvent can also be set to 5 times, 8 times, 12 times, 15 times, etc. of the weight of the avermectin paste as needed. In one embodiment, the usage amount of ethanol solvent is 2.5 times the weight of the avermectin paste, and the usage amount of ethanol solvent can also be set to 2 times, 2.2 times, 2.8 times, 3 times, etc. of the weight of the avermectin paste as needed.
[0032] By adopting the above technical scheme, the usage amount of toluene solvent is optimized, so that the avermectin paste is fully dissolved in the toluene solvent. The usage amount of ethanol solvent is optimized, so that the purified paste is fully dissolved in the ethanol solvent, and the crystallization of avermectin is facilitated.
[0033] Optionally, in step S3, the number of cooling crystallization is 1-5 times. In one embodiment, the number of cooling crystallization is 3 times, and the number of cooling crystallization can also be set to 1 time, 2 times, 4 times, or 5 times as needed.
[0034] Optionally, in step S3, the cooling crystallization adopts gradient cooling crystallization, and the gradient cooling crystallization adopts the following method: first cool to 40-45°C at a rate of 1-2°C / h, keep warm for 20-40 minutes, then cool to 25-30°C at a rate of 2-3°C / h, and keep warm for 1-2 hours.
[0035] By adopting the method of gradually cooling, the solubility of avermectin can be gradually reduced, so that it slowly reaches a saturated state. Further, it is convenient for avermectin crystal nucleus molding, and the crystal nucleus has uniformity, reducing the situation of avermectin crystal nucleus aggregation or the occurrence of lumps. Further, the avermectin crystal nucleus is slowly grown to maintain the stability of crystal nucleus growth. In the present application, by adopting gradient cooling crystallization, the avermectin product is kept with good performance and production stability.
[0036] Optionally, in step S2, the reduced pressure distillation temperature is 70-80°C and the pressure is 0.06-0.09MPa.
[0037] By adopting the above technical solution, it is convenient to remove toluene in the upper liquid.
[0038] In a second aspect, the present application provides an avermectin, using the following technical solution:
[0039] A kind of avermectin, the avermectin is obtained by adopting the above-mentioned method for purifying avermectin and removing RRT0.49 impurities.
[0040] In summary, this application has at least the following beneficial effects:
[0041] 1. The present invention discloses a method for purifying avermectin and removing RRT0.49 impurities. The composite detergent adopts a mixture of water and ethanol. Through the cooperation of water and ethanol, the RRT0.49 impurity content in the avermectin product is less than 0.3%, which effectively reduces the RRT0.49 impurity in the avermectin product. Moreover, the avermectin product maintains a high avermectin B1a content, which is greater than 90%.
[0042] 2. In step S1 of the present application, the open-cell sodium chloride particles are added after the composite detergent, which not only compensates for the reduction in the yield of avermectin caused by the excessive addition of water in the composite detergent, but also increases the yield of avermectin, with the highest yield of avermectin reaching 94.68%. At the same time, the RRT0.49 impurity content is further reduced and the avermectin B1a content is increased, showing a good comprehensive effect. DETAILED DESCRIPTION
[0043] In order to make the present application easier to understand, the present application will be further described in detail below in conjunction with the examples, which are merely illustrative and are not intended to limit the scope of application of the present application. The raw materials or components used in the present application can be obtained through commercial routes or conventional methods unless otherwise specified.
[0044] Preparation Example
[0045] Preparation Example 1
[0046] A kind of open-pore sodium chloride granules, which are prepared by the following method:
[0047] Sa. Stir 70 g of sodium chloride coarse powder, 30 g of sodium chloride fine powder, and 1 g of polyvinyl alcohol for 30 min to obtain a mixture.
[0048] The particle size of the sodium chloride coarse powder is 50-100 μm in continuous gradation; the sodium chloride fine powder is 1-50 μm in continuous gradation; and the polyvinyl alcohol is selected from polyvinyl alcohol 2488 of Shandong Tianfeng Chemical Technology Co., Ltd.
[0049] Sb. Take the mixture obtained in step Sa. Under constant stirring, spray 5g of saturated sodium chloride aqueous solution into the mixture, and the saturated sodium chloride aqueous solution is sprayed within 20 minutes. After spraying is completed, stir for 30 minutes. Then, press and shape at a pressure of 12t to obtain a primary finished product.
[0050] Sc. Keep the temperature at 90°C for 30 minutes. Raise the temperature to 120°C and keep the temperature for 60 minutes. Raise the temperature to 880°C and keep the temperature for 4 hours. Lower the temperature to 25°C to obtain open-pore sodium chloride particles.
[0051] Among them, the average particle size of the open-pore sodium chloride particles is 5 mm.
[0052] Preparation Example 2
[0053] A porous sodium chloride particle, which is different from Example 1 in that, in the preparation method of the porous sodium chloride particle, an equal amount of water is used to replace the saturated sodium chloride solution.
[0054] Preparation Example 3
[0055] A perforated sodium chloride particle, which is different from Example 1 in that polyvinyl alcohol is not added in step Sa of the perforated sodium chloride particle preparation method.
[0056] Example
[0057] Table 1 Amount of raw materials added in the method for avermectin purification and removal of RRT0.49 impurities (unit: part)
[0058]
[0059] Note: Each portion is 80g.
[0060] Example 1
[0061] A method for purifying avermectin and removing RRT0.49 impurities, the raw materials and proportions used are shown in Table 1, and the method comprises the following steps:
[0062] S1. Weigh the avermectin paste, add the avermectin paste to a toluene solvent, heat to 70°C, and stir for 3 hours. Then add the composite detergent, keep warm and stir for 1 hour. Then keep warm and stand until layers are separated, and separate while hot to obtain an upper layer liquid and a lower layer liquid.
[0063] The avermectin paste is obtained by evaporating ethanol in the evaporation section, that is, the avermectin paste is obtained by concentrating and removing ethanol, and the content of avermectin B1a in the avermectin paste is 35%. The composite detergent is a mixture of water and ethanol.
[0064] S2. Take the upper liquid obtained in step S1 and distill the upper liquid at a temperature of 80° C. and a pressure of 0.06 MPa until there is no fraction, thereby obtaining a purified paste.
[0065] S3, take the purified paste obtained in step S2. Then add ethanol solvent to the purified paste, heat to 75 ° C, stir for 3h, then cool to 45 ° C at a rate of 2 ° C / h, keep warm for 30min, then cool to 30 ° C at a rate of 3 ° C / h, keep warm for 1.5h, filter, and complete primary crystallization. Then add 200g of ethanol solvent, repeat the above steps, and complete secondary crystallization. Then add 200g of ethanol solvent, repeat the above steps, and complete three crystals. Afterwards, dry to constant weight at a temperature of 80 ° C to obtain an avermectin product.
[0066] Embodiment 2-7
[0067] A method for purifying avermectin and removing RRT0.49 impurities is different from Example 1 in that in step S1, the amount of water / ethanol used in the composite detergent is different, and the raw materials and proportions used are shown in Table 1.
[0068] Example 8
[0069] A method for purifying avermectin and removing RRT0.49 impurities, which is different from Example 6 in that the raw materials also include open-pore sodium chloride particles, and the open-pore sodium chloride particles are added after the composite detergent is added and the mixture is stirred and heated for 1 hour. The open-pore sodium chloride particles are prepared by Preparation Example 1, and the raw materials and proportions used are shown in Table 1.
[0070] Step S1 is specifically as follows: weighing avermectin paste, then adding the avermectin paste into a toluene solvent, heating to 70°C, and stirring for 3 hours. Then adding a composite detergent, keeping warm and stirring for 1 hour. Then adding open-cell sodium chloride particles, and continuing to keep warm and stirring for 30 minutes. Then keeping warm and standing until stratification, separating while hot, and obtaining an upper layer liquid and a lower layer liquid.
[0071] Example 9
[0072] A method for purifying avermectin and removing RRT0.49 impurities, which is different from Example 8 in that the sources of the open-pore sodium chloride particles are different, and the open-pore sodium chloride particles are prepared by Preparation Example 2.
[0073] Example 10
[0074] A method for purifying avermectin and removing RRT0.49 impurities, which is different from Example 8 in that the sources of the open-pore sodium chloride particles are different, and the open-pore sodium chloride particles are prepared by Preparation Example 3.
[0075] Embodiment 11
[0076] A method for purifying avermectin and removing RRT0.49 impurities, which differs from Example 8 in that, in step S1, an equal amount of sodium chloride coarse powder is used to replace the open-pore sodium chloride particles.
[0077] Comparative Example
[0078] Comparative Example 1
[0079] A method for purifying avermectin and removing RRT0.49 impurities, which differs from Example 1 in that in step S1, the composite detergent is replaced with an equal amount of water.
[0080] Performance Testing
[0081] The avermectin products obtained in Examples 1-11 and Comparative Example 1 were taken as samples, and the following performance tests were performed. The test results are shown in Table 2.
[0082] The sample was tested by high performance liquid chromatography, and the content of RRT0.49 impurity and avermectin B1a were calculated by area normalization method. High performance liquid chromatography testing conditions: chromatographic column ods25μm 4.6×150mm; column temperature 25°C; detection wavelength 245nm; mobile phase methanol: water = 80:20; flow rate 1.0mL / min.
[0083] Table 2 Test results
[0084] Test items RRT0.49 impurity content / (%) Avermectin B1a content / (%) Avermectin yield / (%) Example 1 0.21 91.56 93.45 Example 2 0.28 90.07 93.88 Example 3 0.18 92.21 92.46 Example 4 0.22 91.36 93.66 Example 5 0.20 91.88 93.24 Example 6 0.19 91.96 92.57 Example 7 0.18 92.23 91.88 Example 8 0.09 94.15 94.68 Example 9 0.11 93.71 94.11 Example 10 0.12 93.52 94.22 Embodiment 11 0.17 92.42 93.87 Comparative Example 1 0.54 84.54 94.21
[0085] As can be seen from Table 2, the avermectin product obtained by the method for purifying avermectin and removing RRT0.49 impurities of the present application has a lower RRT0.49 impurity content of 0.09-0.28%. It also has a higher avermectin B1a content of 90.07-94.15%. At the same time, a good avermectin yield is maintained, the avermectin yield is 91.88-94.68%, and the avermectin yield is greater than 91%.
[0086] Comparing Examples 1-3, it can be seen that as the amount of ethanol added in the composite detergent increases, the RRT0.49 impurity content continues to decrease and tends to be flat, but the avermectin yield continues to decrease. This is mainly due to the fact that part of the avermectin is dissolved in the ethanol of the composite detergent, resulting in a decrease in the avermectin yield. And when the weight ratio of toluene solvent, water, and ethanol is 10:1.5:0.5, a good comprehensive effect is shown.
[0087] By comparing Example 1 and Examples 4-7, it can be seen that with the continuous increase in the amount of water added in the composite detergent, the RRT0.49 impurity content does not change significantly, but the avermectin yield continues to decrease. This may be due to the excessive amount of water added, which causes the amount of toluene to be too small, thereby affecting the stratification of toluene and the composite detergent and affecting the avermectin yield.
[0088] Comparing Example 6, Example 8, and Example 11, it can be seen that adding the open-cell sodium chloride particles after adding the composite detergent can significantly reduce the RRT0.49 impurity content and increase the avermectin B1a content, and at the same time not only compensates for the reduction in avermectin yield caused by excessive water addition, but also increases the avermectin yield. Combined with Examples 8-10, in the preparation method of the open-cell sodium chloride particles, adding polyvinyl alcohol and saturated sodium chloride solution can further increase the use effect of the open-cell sodium chloride particles.
[0089] It should be noted that the embodiments described above are only used to explain the present application and do not constitute any limitation to the present application. The present application is described with reference to typical embodiments, but it should be understood that the words used therein are descriptive and explanatory words, rather than restrictive words. The present application may be modified as specified within the scope of the claims of the present application, and the present invention may be revised without departing from the scope and spirit of the present application. Although the present application described therein relates to specific methods, materials and embodiments, it does not mean that the present application is limited to the specific examples disclosed therein. On the contrary, the present application can be extended to all other methods and applications with the same functions.
Claims
1. A method for purifying avermectin and removing RRT0.49 impurities, characterized in that: The steps include: S1. Add avermectin paste to toluene solvent, heat to 70-75° C., stir to dissolve, then add compound detergent, keep warm and stir for 1-3 hours, add open-cell sodium chloride particles, continue to keep warm and stir for 20-40 minutes, keep warm and stand until stratification, separate while hot to obtain upper liquid and lower liquid; S2, distilling the upper liquid under reduced pressure to obtain a purified paste; S3, adding ethanol solvent to the purified paste, heating to 70-75° C., stirring to dissolve, cooling to crystallize, filtering, drying, and obtaining an avermectin product; The composite detergent is a mixture of water and ethanol, the weight ratio of the toluene solvent, water and ethanol is 10:(1-4):(0.4-0.6); the weight ratio of the toluene solvent and the open-pore sodium chloride particles is 10:(0.1-0.2); the average particle size of the open-pore sodium chloride particles is 3-7 mm; The open-cell sodium chloride particles are prepared by the following method: Sa. Stir and mix the sodium chloride coarse powder, sodium chloride fine powder and polyvinyl alcohol to obtain a mixture; Sb, spray saturated sodium chloride aqueous solution into the mixture under continuous stirring, stir evenly, and then press and form at a pressure of 10-15t to obtain a primary finished product; Sc, at a temperature of 80-90°C, heat preservation for 20-40 minutes, heat to 110-120°C, heat preservation for 50-70 minutes, heat to 850-900°C, heat preservation for 3-5 hours, cool down, and obtain open-pore sodium chloride particles; The particle size of the sodium chloride coarse powder is 50-100 μm in continuous grading, the particle size of the sodium chloride fine powder is 1-50 μm in continuous grading, and the weight ratio of the sodium chloride coarse powder, the sodium chloride fine powder, the polyvinyl alcohol and the saturated sodium chloride aqueous solution is (65-75):(25-35):(0.5-1.5):(4-6).
2. A method for purifying avermectin and removing RRT0.49 impurities according to claim 1, characterized in that: The weight ratio of the toluene solvent, water and ethanol is 10:1.5:0.
5.
3. A method for purifying avermectin and removing RRT0.49 impurities according to claim 1, characterized in that: The content of avermectin B1a in the avermectin paste is 30-40%.
4. A method for purifying avermectin and removing RRT0.49 impurities according to claim 1, characterized in that: The usage amount of the toluene solvent is 5-15 times of the weight of the avermectin paste.
5. A method for purifying avermectin and removing RRT0.49 impurities according to claim 1, characterized in that: The usage amount of the ethanol solvent is 2-3 times of the weight of the avermectin paste.
6. A method for purifying avermectin and removing RRT0.49 impurities according to claim 1, characterized in that: In step S3, the cooling crystallization is performed 1 to 5 times.
7. A method for purifying avermectin and removing RRT0.49 impurities according to claim 1, characterized in that: In step S3, the temperature reduction crystallization adopts gradient temperature reduction crystallization, and the gradient temperature reduction crystallization adopts the following method: first, the temperature is reduced to 40-45°C at a rate of 1-2°C / h, and the temperature is kept for 20-40 minutes, and then the temperature is reduced to 25-30°C at a rate of 2-3°C / h, and the temperature is kept for 1-2 hours.
8. A method for purifying avermectin and removing RRT0.49 impurities according to claim 1, characterized in that: In step S2, the reduced pressure distillation temperature is 70-80°C and the pressure is 0.06-0.09 MPa.
Citation Information
Patent Citations
Avermectin crystallization method
CN109400662A