A pleuromutilin extraction system

Abstract

The utility model relates to the technical field of industrial production of pleuromutilin, and specifically discloses a pleuromutilin extraction system to solve the problems of low yield, insufficient purity and low efficiency of clarity treatment in the existing pleuromutilin extraction mode, which comprises a three-stage countercurrent leaching system, a double-effect evaporation system, a methanol evaporation kettle, a layered tank and a vacuum evaporation crystallization system connected in sequence from the head to the tail. The three-stage countercurrent leaching system comprises three countercurrent leaching tanks and dryers connected in series from the head to the tail, and the discharge end of the first countercurrent leaching tank and the discharge end of the second countercurrent leaching tank are both provided with a slag excavator, and the discharge end of the third countercurrent leaching tank is provided with a slag extruder. The extraction system is used for extracting and processing pleuromutilin, and the pleuromutilin has high yield, high degree of automation and high purity.

Description

Technical Field

[0001] This utility model relates to the field of industrial production technology of truncated pleurotin, and more specifically, to a truncated pleurotin extraction system. Background Technology

[0002] Pleuroromutilin is a tricyclic diterpenoid broad-spectrum antibiotic, first isolated in 1951 by Kavanagh et al. from basidiomycetes *Pleurotus mutilis* and *P. passeckerianus*. Pleuroromutilin possesses excellent antibacterial activity, effectively inhibiting most Gram-positive bacteria, mycoplasma, and some Gram-negative bacteria, and is widely used in veterinary clinical practice. In recent years, researchers have developed derivatives using pleuroromutilin as a prodrug, exhibiting enhanced antibacterial activity against bacteria and mycoplasma, such as tiamulin, vornimulin, azamorin, and retapalline. Pleuroromutilin antibiotics primarily act on the 50S ribosomal subunit of bacteria, blocking bacterial protein synthesis by inhibiting peptidyl transferase activity. Its unique antibacterial mechanism gives it good antibacterial activity against drug-resistant bacteria, and it also has the advantage of not easily developing cross-resistance with other drugs. Therefore, the development of oral derivatives of this class of antibiotics has attracted much attention in recent years.

[0003] Currently, the industry commonly uses single or multiple extraction processes with single or combined organic solvents such as 4-methyl-2-pentanone, acetone, methanol, butyl acetate, ethyl acetate, and ethanol to extract truncated pleurotin mycelium. For example, patent CN102633642A discloses a method for preparing truncated pleurotin crystals, using acetone to extract pleurotin mycelium. However, acetone is highly toxic and a controlled precursor chemical, making it unsuitable for industrial production. Another example is patent CN117466736A, which discloses a dual-solvent extraction method for truncated pleurotin, using methanol for three extractions of the mycelium. This method has low automation, high labor intensity, and a long production cycle.

[0004] Pleurotus truncatedis, as a veterinary drug, has strict quality standards, among which clarity is one of the most important indicators for measuring the quality of raw materials. Clarity is directly related to the purity and efficacy of the drug. In practical applications, the clarity of the drug not only affects its absorption and distribution in animals, but may also affect its therapeutic effect and safety. However, the industry does not pay enough attention to clarity, and generally adopts repeated recrystallization methods, which, although improving purity, also reduce yield and increase production costs and labor intensity. Utility Model Content

[0005] The purpose of this invention is to solve the problems of low yield, insufficient purity, and inefficient clarification treatment in existing truncated pleurotin extraction methods. This application provides a truncated pleurotin extraction system. Using this system to extract truncated pleurotin results in high yield, high degree of automation, and high purity of the extracted truncated pleurotin.

[0006] This utility model is achieved through the following technical solution:

[0007] This utility model provides a truncated pleurotin extraction system, including a three-stage countercurrent leaching system, a double-effect evaporation system, a methanol evaporation kettle, a layered tank, and a reduced pressure crystallization system connected end to end. The three-stage countercurrent leaching system includes three countercurrent leaching tanks and a dryer connected end to end. The discharge ends of the first and second countercurrent leaching tanks are equipped with slag removers, and the discharge end of the third countercurrent leaching tank is equipped with a slag extruder.

[0008] Preferably, the top of the countercurrent extraction tank is provided with a liquid outlet pipe, and multiple liquid outlet pipes are connected to the extraction liquid pipe, which is connected to the double-effect evaporation system.

[0009] Preferably, the discharge end of the slag extruder is also connected to a dryer.

[0010] Preferably, the dual-effect evaporation system includes a buffer tank, a first-effect evaporator, and a second-effect evaporator connected in sequence. A heat circulation pipe is arranged on the top of the first-effect evaporator, and the end of the heat circulation pipe away from the first-effect evaporator is connected to the second-effect evaporator.

[0011] Preferably, the discharge end of the double-effect evaporator is equipped with a discharge pump, and the discharge end of the discharge pump is connected to the methanol evaporation kettle.

[0012] Preferably, the methanol evaporator is equipped with a stirring mechanism in its inner cavity and a heater.

[0013] Preferably, a sprayer is installed on the top of the layered tank, and the discharge end of the layered tank is connected to the depressurization and germination crystallization system.

[0014] Preferably, the reduced pressure regrowth crystallization system includes an acetate concentration kettle, a crystallization kettle, and a dryer connected in sequence, with the feed end of the acetate concentration kettle connected to the discharge end of the layered tank.

[0015] The technical solution of this utility model has the following beneficial effects:

[0016] (1) The truncated pleurotin extraction system of this utility model adopts methanol three-stage countercurrent leaching technology. Through the linkage control of screw conveyor and slag removal machine, the continuous and automated leaching of mycelium is realized, the leaching efficiency is significantly improved, and the yield of truncated pleurotin product is significantly increased.

[0017] (2) After the three-stage leaching process, double-effect evaporation, hot water washing and extraction are carried out in sequence. After extraction, an alkaline water washing process is introduced to accurately remove key impurities such as proteins and polysaccharides that affect the clarity of the leaching solution. This avoids the drawbacks of traditional repeated recrystallization and only requires one crystallization to obtain high-purity truncated pleurotin products.

[0018] (3) After the three-stage leaching process, a double-effect evaporation system is adopted to realize the recycling of methanol vapor, reduce energy consumption, and greatly reduce energy consumption; the vacuum drying and solvent recovery process operates in a closed loop, improves resource utilization, and significantly reduces production costs. Attached Figure Description

[0019] Figure 1 This is a schematic diagram of the process of the truncated pleurotin extraction system in this utility model;

[0020] Figure 2 This is a schematic diagram of the three-stage countercurrent leaching system in this utility model;

[0021] Figure 3 This is a schematic diagram of the process of the double-effect evaporation system in this utility model;

[0022] Figure 4 This is a schematic diagram of the reduced pressure evaporation crystallization system of this utility model.

[0023] Figure reference numerals: 1-Three-stage countercurrent leaching system, 11-Countercurrent leaching tank, 111-Discharge pipe, 112-Leachate pipe, 12-Slag remover, 13-Slag extruder, 14-Dryer, 2-Double-effect evaporation system, 21-Buffer tank, 22-Single-effect evaporator, 23-Double-effect evaporator, 24-Discharge pump, 3-Methanol evaporation kettle, 4-Separation tank, 5-Reduced pressure evaporation crystallization system, 51-Acetate concentrate kettle, 52-Crystallization kettle, 53-Dryer. Detailed Implementation

[0024] To make the objectives, technical solutions, and advantages of this utility model clearer, the technical solutions of this utility model will be clearly and completely described below. Where specific conditions are not specified in the embodiments, they are performed under conventional conditions or conditions recommended by the manufacturer; where the manufacturers of instruments, equipment, reagents, or raw materials are not specified, they are all conventional products that can be purchased commercially.

[0025] The following is a detailed embodiment with reference to the accompanying drawings.

[0026] like Figures 1 to 4 As shown, this utility model provides a truncated pleurotin extraction system, including a three-stage countercurrent leaching system 1, a double-effect evaporation system 2, a methanol evaporation kettle 3, a layered tank 4, and a reduced pressure germination crystallization system connected end to end; the three-stage countercurrent leaching system 1 includes three countercurrent leaching tanks 11 connected end to end and a dryer 14, and the discharge ends of the first countercurrent leaching tank 11 and the second countercurrent leaching tank 11 are equipped with slag removers 12, the discharge end of the third countercurrent leaching tank 11 is equipped with a slag extruder 13, and the feed end of the first countercurrent leaching tank 11 is equipped with a mycelium feed pipe and a methanol feed pipe.

[0027] In this embodiment, the top of the countercurrent extraction tank 11 is provided with a liquid outlet pipe 111, and multiple liquid outlet pipes 111 are connected to the extraction liquid pipe 112, which is connected to the double-effect evaporation system 2.

[0028] In this embodiment, the discharge end of the slag extruder 13 is also connected to the dryer 14.

[0029] In this embodiment, the double-effect evaporation system 2 includes a buffer tank 21, a first-effect evaporator 22 and a second-effect evaporator 23 connected in sequence. The top of the first-effect evaporator 22 is equipped with a heat circulation pipe, and the end of the heat circulation pipe away from the first-effect evaporator 22 is connected to the second-effect evaporator 23. The discharge end of the second-effect evaporator 23 is equipped with a discharge pump 24, and the discharge end of the discharge pump 24 is connected to the methanol evaporation kettle 3.

[0030] In this embodiment, the inner cavity of the methanol evaporator 3 is equipped with a stirring mechanism, and the methanol evaporator 3 is also equipped with a heater.

[0031] In this embodiment, a sprayer is installed on the top of the layered tank 4, and the discharge end of the layered tank 4 is connected to the depressurized growth crystallization system.

[0032] In this embodiment, the reduced pressure hair growth crystallization system includes an acetate concentration kettle 51, a crystallization kettle 52 and a dryer 53 connected in sequence from end to end. The feed end of the acetate concentration kettle 51 is connected to the discharge end of the layered tank 4.

[0033] Using this truncated pleurotin extraction system, truncated pleurotin mycelia can be extracted and processed through the following process:

[0034] The first step is to extract the truncated pleurotin mycelium with methanol.

[0035] (1) Methanol and truncated pleurotin mycelium are mixed in a countercurrent extraction tank 11 at a weight ratio of 4:1 to 6:1 and the temperature is maintained at 25 to 40°C. The mycelium moves at a constant speed from the beginning to the end of each stage. After the first stage of countercurrent extraction is completed, the mycelium is transported to the next stage by the slag remover 12 to continue countercurrent extraction until the three stages of extraction are completed.

[0036] (2) After countercurrent leaching, the mycelium is squeezed out by the slag squeezer 13 to discharge the excess leaching liquid from the waste mycelium residue back to the unit. The waste mycelium residue is then conveyed by a screw conveyor into the vacuum paddle dryer 14 for drying. At the same time, methanol is recovered. The drying process is controlled at a temperature of 70℃-90℃ and a pressure of 0Mpa≤-0.07Mpa.

[0037] The second step involves concentrating the extract using a double-effect evaporation system 2, followed by extraction with sec-butyl acetate.

[0038] (1) Continuous input of leachate into the double-effect evaporation system 2: The leachate obtained after three-stage countercurrent leaching is temporarily stored in the buffer tank 21 and pumped to the second-effect evaporator 23. Part of the liquid is transferred to the top film distribution device of the first-effect evaporator 22 by the circulation pump, forming a falling film flow under vacuum and gravity. The shell side steam heating vaporizes the methanol. After the vapor-liquid mixture enters the separation chamber for separation, the methanol vapor is recycled as the heat source of the second effect, and the condensate is recovered to the storage tank for further treatment. When the density of the first-effect concentrate reaches the standard, it is transferred to the evaporation kettle; otherwise, it is returned to continue falling film evaporation. The system controls the temperature of the first effect at 50-75℃, and the second effect is maintained at 35-65℃ by the steam supply of the first effect. The operating pressure is maintained at 0~-0.08Mpa.

[0039] (2) The liquid initially concentrated by the double-effect evaporator is transferred to the methanol evaporator 3 via the double-effect circulating discharge pump 24 for vacuum evaporation. During the vacuum evaporation process, the double-effect concentrate can be continuously received until the batch material reaches 1500±500kg (material concentration = leaching liquid potency × recovered leaching liquid volume / 1000), at which point the receiving of the double-effect concentrate is stopped. During the vacuum evaporation process, the temperature inside the vessel is controlled at 65℃±5℃, and the pressure is 0~-0.08MPa. When it is observed that there is no obvious methanol return in the primary condenser of the methanol evaporator 3 and the material inside the vessel is obviously viscous and granular, the vacuum concentration is stopped.

[0040] (3) Wash with hot water first, then extract with sec-butyl acetate: Pump (2±0.5) m3 of hot water into methanol evaporator 3, start stirring methanol evaporator 3 for 30~60 minutes, then let stand for 30~60 minutes, and remove the upper waste sugar water. Pump 4-6 times the volume of sec-butyl acetate of the batch material into methanol evaporator 3, start stirring and heat to 65℃±5℃, stir for 30~60 minutes, and then press into sec-butyl acetate layering tank 4.

[0041] The third step involves washing the extract in the separation tank 4 with alkaline water to remove impurities.

[0042] After receiving the sec-butyl acetate stratification tank 4, it is sprayed with alkaline water at pH 8-11 for washing. After standing for 2-4 hours, the upper aqueous phase is extracted. Depending on the situation, it is washed 1-2 more times. The amount of water used each time is adjusted according to the clarity of the waste sugar water color. The hot water temperature is controlled at 65±5℃ and the volume is 0.5~1m3.

[0043] The fourth step involves evaporating the separated extract under reduced pressure to crystallize it, followed by centrifugation, filtration, and drying to obtain truncated pleurotin crystals.

[0044] (1) Acetate concentration kettle 51 vacuum evaporation: Acetate concentration kettle 51 receives acetate solution from the separator and performs vacuum evaporation. The temperature is controlled at 65℃±5℃ and the pressure is -0.08Mpa≤0Mpa. When the concentration is reduced to about 85% of the original volume, the concentration is stopped and the solution is pressed into crystallization kettle 52 to prepare for the next operation.

[0045] (2) Re-evaporation under reduced pressure in crystallization vessel 52: The liquid is evaporated under reduced pressure again in crystallization vessel 52. When the jacket heat source is hot water, the temperature inside the vessel is controlled at 70℃±5℃ and -0.08Mpa≤pressure≤0Mpa. When the jacket heat source is steam, the temperature inside the vessel is controlled at 65℃±5℃ and -0.08Mpa≤pressure≤0Mpa. When a large amount of crystals appear in the material, the concentration is stopped and preparation is made for crystallization centrifugation.

[0046] (3) Cooling and crystallization centrifugation to obtain crystals: After the material is concentrated to a suitable crystallization volume, cooling and crystallization begins. The cooling rate is 3~8℃ / h. After the temperature is reduced to 20~25℃, it is maintained for 30 minutes and then centrifuged to obtain wet crystals.

[0047] (4) Hollow spiral drying to obtain truncated pleurotin crystals: The centrifuged pleurotin crystals are discharged in batches into the hollow spiral dryer 53 for drying. The drying temperature is controlled between 40 and 60°C, and the vacuum degree is controlled between 0 and -0.07 MPa. The drying time is controlled between 40 and 60 minutes according to the weight of a single batch of material and the required drying time. The truncated pleurotin product is obtained. The yield can reach more than 96% and the purity can reach more than 94%.

[0048] The above are merely preferred embodiments of this utility model and are not intended to limit the scope of this utility model. Various modifications and variations can be made to this utility model by those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of this utility model should be included within the protection scope of this utility model.

Claims

1. A truncated pleurotin extraction system, characterized in that, It includes a three-stage countercurrent leaching system (1) connected end to end, a double-effect evaporation system (2), a methanol evaporation kettle (3), a layered tank (4), and a reduced pressure crystallization system; The three-stage countercurrent leaching system (1) includes three countercurrent leaching tanks (11) connected in series. The discharge end of the first countercurrent leaching tank (11) and the discharge end of the second countercurrent leaching tank (11) are equipped with a slag remover (12), and the discharge end of the third countercurrent leaching tank (11) is equipped with a slag extruder (13).

2. The truncated pleurotin extraction system according to claim 1, characterized in that, The countercurrent extraction tank (11) is equipped with a liquid outlet pipe (111) at the top, and multiple liquid outlet pipes (111) are connected to the extraction liquid pipe (112), which is connected to the double-effect evaporation system (2).

3. The truncated pleurotin extraction system according to claim 1, characterized in that, The discharge end of the slag extruder (13) is also connected to a dryer (14).

4. The truncated pleurotin extraction system according to claim 1, characterized in that, The dual-effect evaporation system (2) includes a buffer tank (21), a first-effect evaporator (22), and a second-effect evaporator (23) connected in sequence. A heat circulation pipe is arranged on the top of the first-effect evaporator (22), and the end of the heat circulation pipe away from the first-effect evaporator (22) is connected to the second-effect evaporator (23).

5. The truncated pleurotin extraction system according to claim 4, characterized in that, The discharge end of the double-effect evaporator (23) is equipped with a discharge pump (24), and the discharge end of the discharge pump (24) is connected to the methanol evaporator (3).

6. The truncated pleurotin extraction system according to claim 1, characterized in that, The methanol evaporator (3) is equipped with a stirring mechanism in its inner cavity and a heater.

7. The truncated pleurotin extraction system according to claim 1, characterized in that, A sprayer is installed on the top of the layered tank (4), and the discharge end of the layered tank (4) is connected to the depressurization hair growth crystallization system.

8. The truncated pleurotin extraction system according to claim 1, characterized in that, The reduced pressure germination crystallization system includes an acetate concentration kettle (51), a crystallization kettle (52), and a dryer (53) connected in sequence. The feed end of the acetate concentration kettle (51) is connected to the discharge end of the layered tank (4).

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