Method for efficiently extracting and purifying pleuromutilin

Abstract

The invention relates to a method for efficiently extracting and purifying pleuromutilin, which comprises the following steps of: filtering pleuromutilin fermentation liquor through a plate frame, drying, performing microwave pressurized extraction and concentration through an extraction solvent, adding ionic liquid, adding seed crystal, crystallizing and drying, and finally obtaining a pleuromutilin finished product. According to the method, the pleuromutilin is extracted by combining a microwave pressurized extraction method with an ionic liquid and seed crystal crystallization method, so that the extraction efficiency is effectively improved, the product purity and yield are improved, and industrial production of the pleuromutilin is easy to realize.

Description

Technical Field

[0001] The invention belongs to the technical field of antibiotic extraction, and particularly relates to a method for efficiently extracting and purifying pleuromutilin. Background Art

[0002] Pleuromutilin is a broad-spectrum diterpene antibiotic produced by Pleurotus mutilus. Pleuromutilin and its derivatives can inhibit bacterial protein synthesis at the ribosome level, have unique therapeutic effects on many Gram-positive bacteria and mycoplasma infections, and have no cross-resistance with general antimicrobial drugs, so they are highly valued. As pleuromutilin is used as an intermediate in the preparation of semi-synthetic antibiotics, its market demand continues to emerge, and the demand for pleuromutilin and its derivatives increases year by year.

[0003] At present, the extraction process of pleuromutilin mostly adopts solvent extraction method, that is, the mycelium is separated from the pleuromutilin fermentation liquid by plate and frame filter pressing method, and then extracted with methanol or industrial alcohol. However, in the actual industrial application process, this method has technical problems such as high impurity content in the synthesis process, low product purity and low yield. Although the purity can be improved by secondary purification, the yield is simultaneously reduced and the extraction cycle is prolonged.

[0004] Therefore, there is an urgent need to develop an industrial production method for efficiently extracting and purifying pleuromutilin. Summary of the invention

[0005] The present invention provides a method for efficiently extracting and purifying pleuromutilin, which extracts pleuromutilin by combining a microwave pressure extraction method with an ionic liquid plus seed crystallization method, thereby effectively improving the extraction efficiency, while also improving the product purity and yield, and facilitating the industrial production of pleuromutilin.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is:

[0007] A method for efficiently extracting pleuromutilin comprises the following steps:

[0008] (1) Pretreatment step: filtering the pleuromutilin fermentation broth through a plate and frame filter to separate the solid and liquid to obtain a mycelium filter cake;

[0009] (2) Drying step: drying the filter cake obtained in step (1) by rotary flash drying to obtain pleuromutilin flash powder;

[0010] (3) extraction step: adding the flash powder obtained in step (2) to an extraction solvent and extracting by microwave pressure to obtain a pleuromutilin extract;

[0011] (4) a concentration step: concentrating the extract obtained in step (3) to obtain a pleuromutilin concentrate;

[0012] (5) Purification step: the concentrated solution obtained in step (4) is mixed with an ionic liquid, seeded with crystals, and then dried to obtain a refined pleuromutilin product.

[0013] Wherein, the fermentation broth in step (1) is the fermentation broth of the basidiomycete Pleurotus sp.

[0014] Wherein, in step (3), the microwave power of the microwave pressurized extraction is 600-680W, the extraction time is 30-60min, the concentration temperature is 50-100°C, and the pressure is 0.2-0.4MPa.

[0015] Wherein, the leaching solvent in step (3) is butyl acetate.

[0016] Wherein, the concentration in step (4) is falling film concentration, the vacuum pressure is -0.01 to -0.10 MPa, and the temperature is 60 to 90°C.

[0017] Wherein, the ionic liquid in step (5) is 1-ethyl-3-methylimidazole diethyl phosphate.

[0018] Wherein, the crystallization method in step (5) is to add seed crystals to control crystallization.

[0019] Wherein, the feed ratio in step (5) is W PL折纯 (Amount of fermentation broth converted into pleuromutilin): V 离子液体 =1:4~10, in the gradient crystallization process, after the temperature rises to 60~80℃, it drops from 75℃ to 40℃, and then drops from 40℃ to 10~15℃, seed crystals are added and the temperature is slowly lowered to 0℃, the cooling rate is controlled at 2~6℃ / h, the stirring speed is 10~40r / min, the stirring is stopped after the crystals are precipitated, and the crystal is grown for 70~120min.

[0020] Wherein, the seed crystals in step (5) are pleuromutilin seed crystals, and the amount used is W 晶种 :W PL折纯 (fermentation broth converted to pleuromutilin) ​​= 1:80-150.

[0021] More preferably, the seed crystal particle size is 75 to 120 μm, and the seed crystal purity is greater than or equal to 99.5.

[0022] The technical solution of the present invention has at least the following beneficial technical effects:

[0023] 1. The extraction of pleuromutilin by microwave extraction combined with pressurization accelerates the separation of pleuromutilin from the filter cake and its entry into the solvent. On the one hand, due to the microwave effect, the internal temperature of the cells rises rapidly, exceeding the pressure of the cell wall, causing the cells to rupture and the effective components to diffuse freely into the solvent; on the other hand, under the action of the microwave field, the diffusion rate of pleuromutilin molecules into the material is shortened, thereby increasing the extraction rate by several times, and reducing the time for the extraction temperature to rise, ensuring the extraction quality, and extracting all pleuromutilin units in the fungus residue to the maximum extent, with almost no unit potency residue, which is extremely friendly to the environment, greatly improving the extraction efficiency of pleuromutilin, saving solvents, and reducing the loss of extractants. The overall steps have no odor and safety hazards, creating a good working environment for operators and reducing environmental pressure. Most of the domestic extraction process steps are cumbersome. The use of this technology can greatly reduce manpower, material resources and time costs, and truly achieve energy saving, consumption reduction, low-carbon recycling. This method improves the extraction efficiency by 5 to 10 times higher than the ordinary extraction method, and the mycelium after extraction has basically no residual potency units and other significant advantages.

[0024] 2. Ionic liquids are environmentally friendly green solvents, molten salts composed of organic cations and inorganic or organic ions, which are in liquid state at room temperature or near room temperature. Ionic liquids not only have the advantages of traditional organic solvents, but also show many excellent properties compared with organic solvents, such as non-volatility, non-flammability, wide liquid range, strong solubility, and adjustable functions. In the process of refining pleuromutilin, impurities (such as pigments, proteins, inorganic salts, etc.) in the concentrate are dissolved in the ionic liquid, making the purity of pleuromutilin higher.

[0025] 3. Adding seed crystals during crystallization stabilizes the pleuromutilin crystal form, which helps to ensure the stability of the product during production and storage, improve its bioavailability, enhance its efficacy, increase the particle size and uniformity of the crystals, and ensure the safety, effectiveness and stability of the product. After adding crystals, similar molecules or ions can be induced to arrange into the desired crystal form, accelerate the crystallization speed, and minimize the generation of inefficient and ineffective crystal forms. DETAILED DESCRIPTION

[0026] The embodiments of the present invention will be described clearly and completely below in conjunction with the examples. Obviously, the described examples are only some examples of the present invention, rather than all examples. The following description of at least one exemplary embodiment is actually only illustrative and is by no means intended to limit the present invention and its application or use. Based on the examples in the present invention, all other examples obtained by ordinary technicians in the field without creative work are within the scope of protection of the present invention.

[0027] The pleuromutilin fermentation liquid in the following examples is obtained by fermentation of the basidiomycete Pleurotus sp. The fermentation process is a conventional process, and the commonly used carbon sources in the fermentation medium are mainly soybean oil and glucose; the commonly used nitrogen sources are mainly corn steep liquor, yeast powder, etc. The fermentation cycle is generally about 200 to 330 hours, and the fermentation culture is completed with a titer of 18000 to 24000 U / ml.

[0028] Example 1

[0029] 1. Filter

[0030] The pleuromutilin fermentation liquid with a titer of 23000U / ml and a volume of 100㎡ was filtered through a plate and frame filter press. After feed pressing and reflux, when almost no filtrate flowed out of the plate and frame filtrate outlet, the filter cake was unloaded and put into a rotary flash dryer.

[0031] 2. Drying

[0032] The air inlet temperature of the rotary flash dryer was controlled at 150°C, the air outlet temperature was controlled at 75°C, and the feeding frequency was controlled at 35 Hz. The dried mycelium was conveyed to the microwave extraction system tank by a screw conveyor.

[0033] 3. Extraction

[0034] Press W 闪蒸粉 :V 醋酸丁酯 =1:3.5 ratio into the microwave extraction system tank, open the system tank to stir, put the weighed flash powder into the tank, start stirring at 220r / min, microwave power is 635W, extraction time is 35min, temperature is 70℃, pressure is 0.22MPa, the filter residue after leaching and filtration is dried in a dryer and then comprehensively recovered. The residual titer of pleuromutilin in the filter residue is 18U / ml.

[0035] 4. Concentration

[0036] The extract was pumped into a double-effect evaporator, the liquid phase temperature of the first-effect separation chamber was controlled at 85°C, and the liquid phase temperature of the second-effect separation chamber was controlled at 65°C, most of the solvent in the extract was evaporated, and the concentrated liquid was pressed into the extraction kettle. The concentration was continued at a temperature of 72°C and a vacuum pressure of -0.06MPa. The concentration was stopped when the color of the feed liquid was dark brown and turbid.

[0037] 5. Crystallization

[0038] Add the material into the crystallization tank according to the feed ratio W PL折纯 :V 1-乙基-3-甲基咪唑磷酸二乙酯盐=1:7, add 1-ethyl-3-methylimidazole diethyl phosphate, stir at a rate of 50r / min, heat the concentrated solution to 80°C, then drop from 80°C to 40°C, and then drop from 40°C to 12°C, then add pleuromutilin seed crystals (seed size 95μm, purity 99.5%), the amount is W 晶种 :W PL折纯 =1:120, after 15 minutes, the stirring speed is adjusted to 25r / min, and the temperature is slowly lowered to below 0°C, the cooling rate is 4°C / h, and the temperature is kept for 80 minutes. Finally, the finished product is obtained after crystallization, drying and mixing. The content of pleuromutilin is measured to be 99.4%, and the total yield is 97.3%.

[0039] Example 2

[0040] 1. Filter

[0041] The pleuromutilin fermentation liquid with a titer of 26300U / ml and a volume of 100㎡ was filtered through a plate and frame filter press. After feed pressing and reflux, when almost no filtrate flowed out of the plate and frame filtrate outlet, the filter cake was unloaded and put into a rotary flash dryer.

[0042] 2. Drying

[0043] The air inlet temperature of the rotary flash dryer was controlled at 145°C, the air outlet temperature was controlled at 80°C, and the feeding frequency was controlled at 39 Hz. The dried mycelium was conveyed to the microwave extraction system tank by a screw conveyor.

[0044] 3. Extraction

[0045] Press W 闪蒸粉 :V 醋酸丁酯 =1:2.8 ratio into the microwave extraction system tank, open the system tank to stir, put the weighed flash powder into the tank, start stirring at 230r / min, microwave power of 630W, extraction time of 32min, temperature of 78℃, pressure of 0.25MPa, the filter residue after leaching and filtration is dried in a dryer and then comprehensively recovered. The residual titer of pleuromutilin in the filter residue is 15U / ml.

[0046] 4. Concentration

[0047] The extract was pumped into a double-effect evaporator, the liquid phase temperature of the first-effect separation chamber was controlled at 90°C, and the liquid phase temperature of the second-effect separation chamber was controlled at 70°C, most of the solvent in the extract was evaporated, and the concentrated liquid was pressed into the extraction kettle. The concentration was continued at a temperature of 73°C and a vacuum pressure of -0.08MPa. The concentration was stopped when the color of the feed liquid was dark brown and turbid.

[0048] 5. Crystallization

[0049] Add the material into the crystallization tank according to the feed ratio W PL折纯 :V1-乙基-3-甲基咪唑磷酸二乙酯盐 =1:9, add 1-ethyl-3-methylimidazole diethyl phosphate, stir at 45r / min, heat the concentrated solution to 75°C, then drop from 75°C to 40°C, and then drop from 40°C to 13°C, then add pleuromutilin seed crystals (seed size 110μm, purity 99.6%, amount W 晶种 :W PL折纯 =1:130, after 15 minutes, the stirring speed was adjusted to 28r / min, and the temperature was slowly lowered to below 0°C, the cooling rate was 5°C / h, and the temperature was kept for 105 minutes. Finally, the finished product was obtained after crystallization, drying and mixing. The content of pleuromutilin was measured to be 99.7%, and the total yield was 97.1%.

[0050] Example 3

[0051] 1. Filter

[0052] The pleuromutilin fermentation liquid with a titer of 25620U / ml and a volume of 100㎡ was filtered through a plate and frame filter press. After feed pressing and reflux, when almost no filtrate flowed out of the plate and frame filtrate outlet, the filter cake was unloaded and put into a rotary flash dryer.

[0053] 2. Drying

[0054] The air inlet temperature of the rotary flash dryer was controlled at 160°C, the air outlet temperature was controlled at 85°C, and the feeding frequency was controlled at 41 Hz. The dried mycelium was conveyed to the microwave extraction system tank by a screw conveyor.

[0055] 3. Extraction

[0056] Press W 闪蒸粉 :V 醋酸丁酯 =1:3 ratio of butyl acetate into the microwave extraction system tank, open the system tank to stir, put the weighed flash powder into the tank, start stirring at 200r / min, microwave power of 655W, extraction time of 38min, temperature of 75℃, pressure of 0.23MPa, the filter residue after leaching and filtration is dried in a dryer and then comprehensively recovered. The residual titer of pleuromutilin in the filter residue is 15U / ml.

[0057] 4. Concentration

[0058] The extract was pumped into a double-effect evaporator, the liquid phase temperature of the first-effect separation chamber was controlled at 95°C, and the liquid phase temperature of the second-effect separation chamber was controlled at 78°C, most of the solvent in the extract was evaporated, and the concentrated liquid was pressed into the extraction kettle. At a temperature of 70°C and a vacuum pressure of -0.07MPa, the concentration was continued until the color of the feed liquid was dark brown and turbid, and the concentration was stopped when it was concentrated.

[0059] 5. Crystallization

[0060] Add the material into the crystallization tank according to the feed ratio WPL折纯 :V 1-乙基-3-甲基咪唑磷酸二乙酯盐 =1:9.5, add 1-ethyl-3-methylimidazole diethyl phosphate, stir at a rate of 42r / min, heat the concentrated solution to 77°C, then drop from 77°C to 40°C, and then drop from 40°C to 11°C, then add pleuromutilin seed crystals (seed size 115μm, purity 99.8%, amount W 晶种 :W PL折纯 =1:140), after 15 minutes, the stirring speed was adjusted to 26r / min, and the temperature was slowly lowered to below 0°C, the cooling rate was 6°C / h, and the temperature was kept for 115 minutes. Finally, the finished product was obtained after crystallization, drying and mixing. The pleuromutilin content was measured to be 99.6%, and the total yield was 96.7%.

[0061] Example 4

[0062] 1. Filter

[0063] The pleuromutilin fermentation liquid with a titer of 24870U / ml and a volume of 100㎡ was filtered through a plate and frame filter press. After feed pressing and reflux, when almost no filtrate flowed out of the plate and frame filtrate outlet, the filter cake was unloaded and put into a rotary flash dryer.

[0064] 2. Drying

[0065] The air inlet temperature of the rotary flash dryer was controlled at 170°C, the air outlet temperature was controlled at 95°C, and the feeding frequency was controlled at 43Hz. The dried mycelium was conveyed to the microwave extraction system tank by a screw conveyor.

[0066] 3. Extraction

[0067] Press W 闪蒸粉 :V 醋酸丁酯 =1:3.5 ratio into the microwave extraction system tank, open the system tank to stir, put the weighed flash powder into the tank, start stirring at 220r / min, microwave power is 635W, extraction time is 29min, temperature is 70℃, pressure is 0.22MPa, the filter residue after leaching and filtration is dried in a dryer and then comprehensively recovered. The residual titer of pleuromutilin in the filter residue is 16U / ml.

[0068] 4. Concentration

[0069] The extract was pumped into a double-effect evaporator, the liquid phase temperature of the first-effect separation chamber was controlled at 85°C, and the liquid phase temperature of the second-effect separation chamber was controlled at 65°C, most of the solvent in the extract was evaporated, and the concentrated liquid was pressed into the extraction kettle. The concentration was continued at a temperature of 72°C and a vacuum pressure of -0.06MPa. The concentration was stopped when the color of the feed liquid was dark brown and turbid.

[0070] 5. Crystallization

[0071] Add the material into the crystallization tank according to the feed ratio W PL折纯 :V 1-乙基-3-甲基咪唑磷酸二乙酯盐 =1:7, add 1-ethyl-3-methylimidazole diethyl phosphate, stir at 50r / min, heat the concentrated solution to 80°C, then drop from 75°C to 40°C, and then drop from 40°C to 12°C, add seed crystals, adjust the stirring speed to 25r / min after 15min, and slowly cool to below 0°C, with a cooling rate of 4°C / h, keep warm for 100min, finally crystallize, dry and mix to obtain the finished product. The pleuromutilin content was measured to be 99.5%, and the total yield was 97.2%.

[0072] Comparative Example 1

[0073] Compared with Example 1, the crystallization method of step 5 is changed in this comparative example, and conventional gradient cooling crystallization is selected.

[0074] 1. Filter

[0075] The pleuromutilin fermentation liquid with a titer of 23740U / ml and a volume of 100㎡ was filtered through a plate and frame filter press. After feed pressing and reflux, when almost no filtrate flowed out of the plate and frame filtrate outlet, the filter cake was unloaded and put into a rotary flash dryer.

[0076] 2. Drying

[0077] The air inlet temperature of the rotary flash dryer was controlled at 150°C, the air outlet temperature was controlled at 75°C, and the feeding frequency was controlled at 35 Hz. The dried mycelium was conveyed to the microwave extraction system tank by a screw conveyor.

[0078] 3. Extraction

[0079] Press W 闪蒸粉 :V 醋酸丁酯 =1:3.5 ratio into the microwave extraction system tank, open the system tank to stir, put the weighed flash powder into the tank, start stirring at 220r / min, microwave power is 635W, extraction time is 33min, temperature is 70℃, pressure is 0.22MPa, the filter residue after leaching and filtration is dried in a dryer and then comprehensively recovered. The residual titer of pleuromutilin in the filter residue is 18U / ml.

[0080] 4. Concentration

[0081] The extract was pumped into a double-effect evaporator, the liquid phase temperature of the first-effect separation chamber was controlled at 85°C, and the liquid phase temperature of the second-effect separation chamber was controlled at 66°C, most of the solvent in the extract was evaporated, and the concentrated liquid was pressed into the extraction kettle, and the concentration was continued at a temperature of 73°C and a vacuum pressure of -0.06MPa. The concentration was stopped when the color of the feed liquid was dark brown and turbid.

[0082] 5. Crystallization

[0083] Add the material into the crystallization tank according to the feed ratio W PL折纯 :V 1-乙基-3-甲基咪唑磷酸二乙酯盐 =1:7, add ionic liquid, stir at 50r / min, raise the temperature of the concentrate to 80°C, keep warm for 120min, then lower the temperature to below 0°C, finally crystallize, dry and mix to obtain the finished product. The pleuromutilin content was 96.2% and the total yield was 95.9%.

[0084] Comparative Example 2

[0085] Compared with Example 1, the extraction method of step 3 is changed in this comparative example, and a microwave normal pressure extraction method is selected.

[0086] 1. Filter

[0087] The pleuromutilin fermentation liquid with a titer of 24510U / ml and a volume of 100㎡ was filtered through a plate and frame filter press. After feed pressing and reflux, when there was almost no filtrate flowing out of the plate and frame filtrate outlet, the filter cake was discharged and transported to a crusher for crushing into powder.

[0088] 2. Drying

[0089] The air inlet temperature of the rotary flash dryer was controlled at 170°C, the air outlet temperature was controlled at 95°C, and the feeding frequency was controlled at 43Hz. The dried mycelium was conveyed to the microwave extraction system tank by a screw conveyor.

[0090] 3. Extraction

[0091] Press W 闪蒸粉 :V 醋酸丁酯 =1:3.5 ratio into the microwave extraction system tank, open the system tank to stir, put the weighed flash powder into the tank, start stirring 215r / min, extraction time is 130min, temperature is 95℃, pressure is 0.15MPa, the filter residue after leaching and filtration is dried in a dryer and then comprehensively recovered. The residual titer of pleuromutilin in the filter residue is 15U / ml.

[0092] 4. Concentration

[0093] The extract was pumped into a double-effect evaporator, the liquid phase temperature of the first-effect separation chamber was controlled at 80°C, and the liquid phase temperature of the second-effect separation chamber was controlled at 65°C, most of the solvent in the extract was evaporated, and the concentrated liquid was pressed into the extraction kettle. The concentration was continued at a temperature of 75°C and a vacuum pressure of -0.06MPa. The concentration was stopped when the color of the feed liquid was dark brown and turbid.

[0094] 5. Crystallization

[0095] Add the material into the crystallization tank according to the feed ratio W PL折纯 :V 离子液体=1:7, add ionic liquid, stir at 54r / min, after the temperature of the concentrate rises to 78°C, it drops from 78°C to 40°C, then from 40°C to 12°C, and slowly drops to below 0°C, the cooling rate is 6°C / h, and the temperature is kept for 105min. At this time, pleuromutilin seed crystals (seed size 95μm, purity 99.9%) are added, and the amount is W 晶种 :W PL折纯 =1:128, after 15 minutes, the stirring speed was adjusted to 20r / min, and the temperature was slowly lowered to below 0°C, the cooling rate was 5°C / h, and the temperature was kept for 80 minutes. Finally, the product was obtained after crystallization, drying and mixing. The content of pleuromutilin was measured to be 99.3%, and the total yield was 97.0%.

[0096] Comparative Example 3

[0097] Compared with Example 1, the extraction method of step 3 is changed in this comparative example, and a conventional extraction method is selected.

[0098] 1. Filter

[0099] The pleuromutilin fermentation liquid with a titer of 23000U / ml and a volume of 100㎡ was filtered through a plate and frame filter press. After feed pressing and reflux, when almost no filtrate flowed out of the plate and frame filtrate outlet, the filter cake was unloaded and put into a rotary flash dryer.

[0100] 2. Drying

[0101] The air inlet temperature of the rotary flash dryer was controlled at 150°C, the air outlet temperature was controlled at 75°C, and the feeding frequency was controlled at 35 Hz. The dried mycelium was conveyed to the microwave extraction system tank by a screw conveyor.

[0102] 3. Extraction

[0103] Press W 闪蒸粉 :V 甲醇 =1:3.5 ratio into the microwave extraction system tank, open the system tank to stir, put the weighed flash powder into the tank, extract and stir for 180min, speed 200r / min, extract 3 times in the same way, dry the filter residue after extraction and filtration in a dryer and then conduct comprehensive recovery treatment. The residual titer of pleuromutilin in the filter residue is 72U / ml.

[0104] 4. Concentration

[0105] The extract was pumped into a double-effect evaporator, the liquid phase temperature of the first-effect separation chamber was controlled at 84°C, and the liquid phase temperature of the second-effect separation chamber was controlled at 63°C, most of the solvent in the extract was evaporated, and the concentrated liquid was pressed into the extraction kettle. At a temperature of 73°C and a vacuum pressure of -0.07MPa, the concentration was continued until the color of the feed liquid was dark brown and turbid, and the concentration was stopped when it was concentrated.

[0106] 5. Crystallization

[0107] Add the material into the crystallization tank according to the feed ratio W PL折纯 :V 1-乙基-3-甲基咪唑磷酸二乙酯盐 =1:8, add 1-ethyl-3-methylimidazole diethyl phosphate, stir at 52r / min, heat the concentrated solution to 81°C, then drop from 81°C to 40°C, and then drop from 40°C to 13°C, then add pleuromutilin seed crystals (seed size 98μm, purity 99.7%), the amount is W 晶种 :W PL折纯 =1:125, after 16 minutes, the stirring speed was adjusted to 27r / min, and the temperature was slowly lowered to below 0°C, the cooling rate was 3°C / h, and the temperature was kept for 75 minutes. Finally, the product was obtained after crystallization, drying and mixing. The pleuromutilin content was measured to be 98.7%, and the total yield was 95.1%.

[0108] The comparison between Example 1 and Comparative Examples 1 to 3 is as follows:

[0109] Serial number contrast Extraction cycle (min) content(%) Yield (%) 1 Example 1 35 99.4 97.3 2 Example 2 32 99.7 97.1 3 Example 3 38 99.6 96.7 4 Example 4 29 99.3 97.2 5 Comparative Example 1 36 96.2 95.9 6 Comparative Example 2 126 99.3 97.0 7 Comparative Example 3 360 98.7 95.1

Claims

1. A method for efficiently extracting pleuromutilin, comprising the following steps: (1) Pretreatment step: filtering the pleuromutilin fermentation broth through a plate and frame filter to separate the solid and liquid to obtain a mycelium filter cake; (2) Drying step: drying the filter cake obtained in step (1) by rotary flash drying to obtain pleuromutilin flash powder; (3) extraction step: adding the flash powder obtained in step (2) to an extraction solvent and extracting by microwave pressure to obtain a pleuromutilin extract; (4) a concentration step: concentrating the extract obtained in step (3) to obtain a pleuromutilin concentrate; (5) Purification step: the concentrated solution obtained in step (4) is mixed with an ionic liquid, seeded with crystals, and then dried to obtain a refined pleuromutilin product.

2. The method for efficiently extracting and purifying pleuromutilin according to claim 1, characterized in that In step (3), the microwave power of the microwave pressure extraction is 600-680W, the extraction time is 30-60min, the concentration temperature is 50-100°C, and the pressure is 0.2-0.4MPa.

3. The method for efficiently extracting and purifying pleuromutilin according to claim 1, characterized in that The leaching solvent in step (3) is butyl acetate.

4. The method for efficiently extracting and purifying pleuromutilin according to claim 1, characterized in that The concentration in step (4) is falling film concentration, the vacuum pressure is -0.01 to -0.10 MPa, and the temperature is 60 to 90°C.

5. The method for efficiently extracting and purifying pleuromutilin according to claim 1, characterized in that The ionic liquid in step (5) is 1-ethyl-3-methylimidazole diethyl phosphate.

6. The method for efficiently extracting and purifying pleuromutilin according to claim 1, characterized in that The crystallization method in step (5) is to add seed crystals to control the crystallization.

7. The method for efficiently extracting and purifying pleuromutilin according to claim 6, characterized in that The seed crystals in step (5) are pleuromutilin seed crystals.

8. The method for efficiently extracting and purifying pleuromutilin according to claim 6, characterized in that The seed crystal particle size in step (5) is 75 to 120 μm, and the seed crystal purity is ≥99.5.