A process for the extraction of erythromycin and / or erythromycin thiocyanate by flotation and a flotation column

Abstract

The present application relates to a method for extracting erythromycin and / or erythromycin thiocyanate by flotation and a flotation column, the method comprising: (1) adding a flotation material liquid containing erythromycin and / or erythromycin thiocyanate into the flotation column, separating erythromycin and / or erythromycin thiocyanate by using foam flotation and / or solvent flotation with air or nitrogen as carrier gas, and obtaining an erythromycin and / or erythromycin thiocyanate enrichment phase / concentrate; (2) treating the enrichment phase / concentrate to obtain erythromycin and / or erythromycin thiocyanate. The present application realizes low-cost and high-efficiency concentration / enrichment of erythromycin / erythromycin thiocyanate and reduces the loss of erythromycin / erythromycin thiocyanate.

Description

Technical Field

[0001] This invention relates to the technical field of erythromycin / erythromycin thiocyanate extraction, specifically to a method and flotation column for flotation extraction of erythromycin and / or erythromycin thiocyanate. Background Technology

[0002] Erythromycin (EM) is a fourteen-membered macrolide antibiotic produced by *Streptomyces erythromycin*. Erythromycin thiocyanate is the thiocyanate of erythromycin. It is not only a veterinary macrolide antibiotic but also an important pharmaceutical intermediate. It is a raw material for the synthesis of a series of erythromycins such as clarithromycin, roxithromycin, and azithromycin, and has significant application value and wide application demand. Erythromycin thiocyanate and erythromycin are biotoxic. For example, erythromycin reduces the activity of microorganisms used in water treatment (Wan Tengfei, Study on the toxicity of low-concentration erythromycin wastewater to microorganisms in acclimatized anaerobic sludge, Neijiang Science and Technology, 2011, 1:35), and also affects the activity of microorganisms in water bodies (Yang Wanwan, Wu Shiqiuxian, Wu Yixiao, Zhang Weihao, Study on the toxicity of enrofloxacin and erythromycin thiocyanate to Microcystis aeruginosa, China Environmental Science, 2013, 33(10):1829-1834; Zhang Jianjiang, Xiao Jianzhong, Chen Siping, Evaluation of the toxicity of three drugs and personal care products by luminescent bacteria, 2023, 30(1):49-52). Its residue will increase the cost of water treatment, and its loss may cause harm to the ecological environment. In industrial production processes, increasing the yield of erythromycin / erythromycin thiocyanate and reducing its residue can not only improve the economic benefits of enterprises, but also reduce water treatment costs caused by erythromycin / erythromycin thiocyanate residue and reduce environmental risks caused by erythromycin / erythromycin thiocyanate loss.

[0003] Industrially, erythromycin and erythromycin thiocyanate are produced through fermentation: Erythromycin fermentation broth is obtained by fermentation with *Streptomyces erythromycin*. Due to the low concentration of erythromycin and the high content of impurities such as bacteria and pigments in the fermentation broth, the broth needs to be filtered to remove bacteria, resulting in a fermentation filtrate. This filtrate is then concentrated and purified (concentration increases the erythromycin concentration to facilitate salt crystallization, while purification primarily removes impurities such as pigments). Salt crystallization (adding potassium thiocyanate or sodium thiocyanate converts erythromycin into erythromycin thiocyanate salt, which crystallizes from the liquid) forms erythromycin thiocyanate salt. Further recrystallization (also known as refining crystallization) and drying processes yield the erythromycin thiocyanate product that meets factory requirements. In industrial production, there are two main methods for concentrating and purifying the filtered fermentation filtrate: one is solvent extraction, and the other involves separating purification and concentration into two steps: first, resin decolorization and purification, followed by nanofiltration concentration. While solvent extraction can simultaneously concentrate and purify, it is limited by the extraction distribution balance, requiring multiple extractions to extract erythromycin from fermentation filtrate, resulting in high solvent consumption, high energy consumption, and low separation efficiency. In another method, purification followed by concentration, the resin regeneration during the resin decolorization step requires a large amount of water, and erythromycin is lost with the regeneration water. Nanofiltration concentrates erythromycin while enriching impurities, causing membrane fouling or even blockage, and membrane cleaning requires a large amount of water, with erythromycin also being lost with the water.

[0004] Currently, the concentration of erythromycin in fermentation broth in China is approximately 3-8 g / L (Chinese Patent CN103159812B; Li Chunling, Niu Shasha, Niu Chun, Shi Yanpeng, Zhang Ping, Selection of high-yield erythromycin strains and optimization of fermentation conditions, Chinese Journal of Veterinary Drugs, 2024, 58(1):37-43.). The extraction of erythromycin from fermentation broth generally begins with filtration to remove bacteria. The filtration process yields approximately 85%-94.8% of the erythromycin (Jin Xin, Basic Research on the Preparation of Macroporous Resin for Chromatographic Separation of Erythromycin A and C, Dissertation). Traditional solvent extraction yields 75-80%, with about 20-25% remaining in the raffinate. Purification using novel extraction techniques (such as aqueous two-phase extraction) yields approximately 75-95% (Zhu Sheng, Basic Research on the Separation of Erythromycin A and its Isomers using Macroporous Resin Adsorption Technology, Dissertation), with about 5-25% of the erythromycin lost. A nanofiltration concentration method following resin decolorization typically results in a loss of about 1-5% of the erythromycin during decolorization, and a nanofiltration concentration yield of approximately 90% (Jin Xin, Basic Research on the Preparation of Macroporous Resin for Chromatographic Separation of Erythromycin A and C, Dissertation), with about 10-20% remaining in the waste liquid from washing the nanofiltration membrane and resin regeneration. Currently, the total yield of erythromycin thiocyanate in domestic production is approximately 70-80% (Chen Dong, Wang Weixing, Bai Hailong, Wang Wenliang, Research on the Recovery Process of Mother Liquor from Erythromycin Thiocyanate Refining, Chemical Industry Management, 2023, 25: 117-119.). 20-30% of erythromycin / erythromycin thiocyanate is lost, remaining in the aforementioned raffinate (or nanofiltration membrane cleaning solution, resin regeneration solution), and approximately 10% remains in the salt crystallization mother liquor and recrystallization mother liquor. Using existing technologies to extract erythromycin / erythromycin thiocyanate results in high production costs (large solvent consumption in solvent extraction; high solvent recovery costs; low yield), and approximately 20-30% of erythromycin remains in the raffinate (or nanofiltration membrane cleaning solution, resin regeneration solution) and crystallization mother liquor, among other production residues.

[0005] To further extract erythromycin / erythromycin thiocyanate from production residues such as fermentation filtrate, crystallization mother liquor, or waste liquids such as nanofiltration membrane cleaning solutions and resin regeneration solutions, researchers proposed two methods: solvent extraction and resin adsorption. Solvent extraction is limited by distribution equilibrium, requiring a sufficiently high initial concentration of the target compound in the feed solution, making it unsuitable for the efficient recovery of low-concentration erythromycin / erythromycin thiocyanate. For residues containing high concentrations of erythromycin, achieving high recovery rates requires large amounts of solvent and kinetic energy to enhance two-phase mixing, involving multiple steps such as mixing and phase separation, resulting in high processing costs and cumbersome procedures. For example, Chinese patent CN103159812B proposes a method for extracting erythromycin from an aqueous solution. Under alkaline conditions (pH = 9-11), erythromycin is extracted from an aqueous solution containing sec-butyl acetate or a mixed extractant containing sec-butyl acetate. The extraction process involves using a filtrate obtained by filtering erythromycin fermentation broth, a concentrate obtained by filtering and then concentrating the erythromycin fermentation broth, or a separated liquid obtained by adsorbing the filtered erythromycin fermentation broth onto an ion exchange resin. The initial concentration of erythromycin in the aqueous solution is 1-200 g / L, the enrichment factor is generally no greater than 4, and the extraction yield is approximately 87-95%. Erythromycin is then separated by freeze crystallization, with a total yield of approximately 85% and a loss of approximately 19-26%. Furthermore, the extraction requires two stages, with the volume ratio of erythromycin aqueous solution to extractant in each stage approximately 1:0.1-1. This results in a large amount of extractant used, necessitating recovery through atmospheric or vacuum distillation, leading to high recovery costs. For example, Chinese patent application CN110950918 A proposes a method for recovering erythromycin thiocyanate from recrystallization mother liquor (erythromycin concentration of approximately 14-17 g / L) using solvent extraction. The steps include multiple stirring and mixing and multiple settling and layering. The supernatant (extract phase) obtained by extraction needs to be washed with water and salted out multiple times to remove emulsions before crystallization. The yield of erythromycin thiocyanate is approximately 68%, and the residual concentration of erythromycin in the crystallization mother liquor is approximately 0.7-0.8 g / L, which can easily cause secondary pollution. Chen Dong et al. (Chen Dong, Wang Weixing, Bai Hailong, Wang Wenliang, Research on the Recovery Process of Mother Liquor from Refined Erythromycin Thiocyanate, Chemical Industry Management, 2023, 117-119.) concentrated the recrystallized mother liquor by rotary evaporation and then extracted it. The yield of erythromycin thiocyanate was about 66.91%, which was about 4.5% higher than that of direct extraction without concentration. Chen Dong et al. also proposed another method, which reused the extractant butyl acetate once (due to the distribution balance limitation, ethyl acetate was reused once). Compared with the use of new butyl acetate, the yield was increased by about 8%, to about 70%, but about 30% of erythromycin / erythromycin thiocyanate remained.The concentration of erythromycin / erythromycin thiocyanate in the recrystallization mother liquor is generally 5–15 g / L (Chen Dong, Wang Weixing, Bai Hailong, Wang Wenliang, Research on Recovery Process of Erythromycin Thiocyanate Refining Mother Liquor, Chemical Industry Management, 2023, 117-119). After recovering erythromycin / erythromycin thiocyanate from the crystallization mother liquor by extraction, the residual concentration of erythromycin / erythromycin thiocyanate in the raffinate is approximately 1.5–4.5 g / L. Resin can adsorb the low concentration of erythromycin / erythromycin thiocyanate in the residual liquor, but to separate erythromycin from the resin, a large amount of liquid is required for elution. The concentration of erythromycin / erythromycin thiocyanate in the eluent is generally lower than that required for crystallization and other processes, and concentration is still needed before erythromycin / erythromycin thiocyanate can crystallize out. Furthermore, resin regeneration requires a large amount of reagents and solvents. Therefore, the resin adsorption method for extracting erythromycin / erythromycin thiocyanate from the residual liquor is costly and difficult to promote in industrial production. For example, Chinese patent application CN105237600 A recovers erythromycin thiocyanate from nanofiltration dialysis water or primary crystallization mother liquor of erythromycin fermentation broth. It uses macroporous resin to adsorb erythromycin in wastewater, and obtains an eluent through adsorption, washing with water or alkaline solution, and elution with eluent. The concentration of erythromycin in the eluent is low, and erythromycin thiocyanate cannot be directly crystallized out. It is necessary to concentrate the eluent by methods such as vacuum distillation before erythromycin thiocyanate can be obtained by crystallization. On the other hand, resin washing and regeneration consume large amounts of water, sodium carbonate, and ethyl acetate, resulting in high processing costs. For example, Chinese patent CN 102199179 B discloses a method for recovering erythromycin from the raffinate of erythromycin fermentation broth (the fresh residue after extraction of the fermentation broth, with an erythromycin concentration of approximately 1-3 g / L). This method uses multi-stage resin adsorption and elution with a solution of distilled water and analytical grade acetone (the volume ratio of distilled water to analytical grade acetone is approximately 10-20%). After multi-stage treatment, the erythromycin concentration in the wastewater is below 1 ppm. However, using resin adsorption to extract erythromycin is costly and difficult to promote in industrial production.

[0006] In the field of analytical chemistry, many environmental samples have low analyte concentrations, complex compositions, and numerous interfering substances, requiring pretreatment such as separation / enrichment before analysis. Using flotation as a pretreatment method for separation / enrichment in environmental sample analysis demonstrates advantages such as high enrichment factor and high separation efficiency. For example, Chinese patent application CN101699255A discloses a method for separating / enriching trace amounts of roxithromycin in the environment and then testing roxithromycin in environmental samples using molecular fluorescence spectrophotometry. This method uses 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid ([Bmim]BF4) as the flotation solvent and sodium carbonate as the salting-out agent. Under the action of inert nitrogen gas, trace amounts of roxithromycin in environmental water samples are separated / enriched by flotation using an ionic liquid aqueous two-phase solvent. For example, Wang Liang et al. introduced a pretreatment method for separating and enriching trace tetracycline antibiotics in the environment by using ionic liquid solvent flotation for analysis and testing of trace tetracycline antibiotics in the environment. They used 5 mL of a mixed solvent of ionic liquid [Bmim]PF6 and ethyl acetate in a volume ratio of 1:1 as the flotation agent. 30% NaCl was added to the flotation solution to adjust the density of the flotation solution so that the ionic liquid floated on top of the flotation solution (Wang Liang, Ma Chunhong, Li Huaming, Yan Yongsheng, Ionic liquid [Bmim]PF6 solvent flotation separation and enrichment-photometric determination of trace tetracycline antibiotics in the environment, Journal of Analytical Science, 2010, 26(1):39-42). The above-mentioned flotation separation / enrichment method is used as a pretreatment for small-volume sample analysis. The flotation feed solution is generally about 50 mL, not exceeding 500 mL. The flotation solvent ionic liquids [Bmim]BF4 or [Bmim]PF6 used are expensive ([Bmim]BF4 is about 300-400 yuan / kg, and [Bmim]BF6 is about 1000-1500 yuan / kg). A large amount of salting-out agent also needs to be added to the flotation feed solution, resulting in high processing costs. Moreover, the added salt residue in the flotation residue increases environmental pressure. Although this method can be used for the pretreatment of small-volume samples for analysis, it is not suitable for large-scale extraction in industrial production. For example, Chinese patent application CN102895803A discloses a method for separating / enriching trace amounts of chloramphenicol using aqueous two-phase solvent flotation. This method uses a small molecule alcohol (one of methanol, ethanol, n-propanol, isopropanol, and acetone) as the flotation agent and an inorganic salt (dipotassium hydrogen phosphate) as the salting-out agent. After flotation with nitrogen gas at a certain flow rate (10-50 mL / min) for a certain time (10-60 min), the upper organic phase is collected, and the chloramphenicol content is detected by high-performance liquid chromatography (HPLC). While this method replaces ionic liquids with small molecule alcohols, reducing the cost of the flotation solvent, the concentration of the dipotassium hydrogen phosphate salting-out agent needs to be higher than 0.3 g / mL for phase separation. The preferred concentration of dipotassium hydrogen phosphate during flotation is 0.6-1.0 g / mL, still requiring the addition of a large amount of salt to the feed solution. This not only increases processing costs but also raises environmental concerns.Chloramphenicol and erythromycin / erythromycin thiocyanate have significantly different structures. Publicly available information shows that for the flotation of similar antibiotics, a large amount of salt needs to be added to the feed solution, and strong polar solvents such as ionic liquids or small molecule alcohols are used as flotation agents. In the field of analytical chemistry, the flotation enrichment of antibiotics requires the addition of large amounts of salt to the feed solution, which is not only costly but also increases environmental pressure due to salt residues, making it unsuitable for industrial application. Furthermore, current flotation enrichment methods are unsuitable for industrial application because of the low concentration of the target analyte. For example, the concentration of roxithromycin in the flotation feed solution of patent CN101699255 A is only about 0.008 mg / mL (0.4 mg / mL of the roxithromycin test solution under study is added to a ground glass joint colorimetric tube, where the volume of the roxithromycin test solution accounts for 1 / 50 of the total solution volume during flotation); the flotation volume is small, not exceeding 500 mL (see appendix). Figure 1 The reasons are as follows: when the concentration of the target substance increases or the feed liquid increases, the backflow of the enriched phase or concentrate to the flotation feed significantly reduces the flotation efficiency. For solvent flotation, backmixing also causes the solvent in the enriched phase to enter the flotation feed, and the contamination of the flotation feed by the enriched phase is not negligible. The movement of a large number of carrier gas bubbles in the flotation feed forms gas-liquid entrainment, causing the flotation feed to enter the concentrate or enriched phase, resulting in a significant reduction in the enrichment factor of the target substance in the concentrate or enriched phase. Gas-liquid entrainment in the concentrate / enriched phase causes the concentrate or enriched phase to be lost with the gas, significantly reducing the flotation efficiency. This not only significantly increases the flotation cost but also causes significant environmental pollution.

[0007] In summary, the concentration of erythromycin / erythromycin thiocyanate in the feed solution treated by the publicly disclosed erythromycin / erythromycin thiocyanate extraction technology used in industrial production needs to be higher than 1 g / L. The concentration of erythromycin / erythromycin thiocyanate in the raffinate or permeate after extraction is generally still higher than 0.5 g / L, resulting in a large amount of residual erythromycin / erythromycin thiocyanate being lost with the water. In the field of analytical chemistry, the flotation technology used for enriching trace antibiotics in environmental samples is costly and difficult to promote and apply in industrial production. This invention discovers that erythromycin / erythromycin thiocyanate has surface activity (see attached diagram). Figure 2 Erythromycin and erythromycin thiocyanate significantly reduce surface tension, making them readily adsorbed at the gas-liquid interface (adsorption at the gas-liquid interface is possible without adding large amounts of salt to the residual liquid / waste liquid generated during the erythromycin / erythromycin thiocyanate production process, such as fermentation filtrate). A flotation extraction technique based on bubble adsorption for erythromycin / erythromycin thiocyanate is proposed for industrial production (see appendix). Figure 3 Erythromycin / erythromycin thiocyanate is efficiently enriched through bubble flotation, achieving low-cost and efficient recovery of erythromycin / erythromycin thiocyanate, reducing the loss of erythromycin / erythromycin thiocyanate during industrial production, improving the economic efficiency of industrial production, and reducing environmental risks and water treatment costs. Summary of the Invention

[0008] The purpose of this invention is to provide a method and flotation column for flotation extraction of erythromycin and / or erythromycin thiocyanate, so as to achieve low-cost and high-efficiency concentration / enrichment / purification of erythromycin / erythromycin thiocyanate and reduce the loss of erythromycin / erythromycin thiocyanate.

[0009] The technical solution of this invention is to use flotation to extract erythromycin and / or erythromycin thiocyanate, disperse a low-cost gas (carrier gas) into bubbles, and use the bubbles to adsorb erythromycin / erythromycin thiocyanate molecules in the feed liquid to achieve low-cost and efficient recovery of low-concentration erythromycin and / or erythromycin thiocyanate, reduce the residue of erythromycin and / or erythromycin thiocyanate, and reduce the loss of erythromycin.

[0010] This invention discovers that erythromycin / erythromycin thiocyanate possesses surface activity and readily adsorbs at the gas-liquid interface, overcoming the partition equilibrium of extraction to achieve high enrichment ratios and efficient separation of low-concentration erythromycin / erythromycin thiocyanate. The flotation process of this invention uses gas as the separation carrier, resulting in low cost. This invention utilizes the selective adsorption of erythromycin or erythromycin thiocyanate by bubbles to remove strongly polar impurities such as pigments and hydrophilic polysaccharides, achieving purification while enriching. After the selective adsorption by bubbles (primary purification), an insoluble organic solvent (such as a moderately polar, weakly polar, or non-polar organic solvent) can be added to the upper layer of the flotation solution for secondary purification, further utilizing the solvent's selectivity to remove impurities, achieving secondary purification while concentrating erythromycin / erythromycin thiocyanate. Figure 4 , Figure 5 and Figure 6 Furthermore, the height of the straight section of the flotation column collection zone in this invention is ≤600mm, effectively reducing the coalescence of bubbles in the collection zone; furthermore, a liquid sealing device is designed to effectively improve backmixing at the interface and increase flotation efficiency; furthermore, a draining component is designed in the liquid sealing device to discharge the entrained flotation feed liquid, while the funnel structure of the draining component reduces the gas velocity, thus reducing the loss of concentrate / enriched phase with the gas. Figure 7-8 ).

[0011] Compared with the prior art, the beneficial effects of the present invention are:

[0012] (1) High efficiency recovery: Erythromycin / erythromycin thiocyanate molecules are captured by bubble adsorption, and the recovery rate can reach 70%-99%. Even for wastewater with a concentration as low as 100mg / L, the recovery rate is still above 70%, which greatly reduces the loss of erythromycin / erythromycin thiocyanate and reduces resource loss.

[0013] (2) Low cost: Erythromycin / erythromycin thiocyanate molecules are captured by bubble adsorption. The separation medium is low cost with gas as carrier. In addition, the flotation process conditions are mild, easy to operate and control, and the equipment investment and operating costs are low.

[0014] (3) Environmentally friendly: It reduces the emission of erythromycin / erythromycin thiocyanate, reduces the pollution pressure on the environment, and helps enterprises achieve clean production and sustainable development. Attached Figure Description

[0015] Figure 1 It is the flotation column used in current antibiotic flotation.

[0016] Figure 2 The effect of erythromycin / erythromycin thiocyanate concentration on the surface tension of aqueous solution;

[0017] Figure 3 This is the process flow for producing erythromycin thiocyanate by flotation extraction of erythromycin from erythromycin fermentation filtrate;

[0018] Figure 4 It is erythromycin fermentation filtrate;

[0019] Figure 5 It is a concentrated solution obtained from the foam flotation of erythromycin fermentation filtrate;

[0020] Figure 6 It is the enriched phase obtained by solvent flotation from the erythromycin fermentation filtrate;

[0021] Figure 7 This is a structural diagram of the flotation column of the present invention;

[0022] Figure 8 This is a top view of the flotation column liquid sealing device of the present invention. Detailed Implementation

[0023] The technical solution of the present invention will be described in detail below with reference to the accompanying drawings and embodiments.

[0024] like Figure 3 As shown, a method for flotation extraction of erythromycin and / or erythromycin thiocyanate, the method comprising:

[0025] (1) Add the flotation feed containing erythromycin and / or erythromycin thiocyanate to the flotation device, using air or nitrogen as the carrier gas, and separate erythromycin and / or erythromycin thiocyanate by flotation to obtain an erythromycin and / or erythromycin thiocyanate enriched phase / concentrate. The flotation is foam flotation (the target substance is adsorbed on the surface of the bubbles and rises to the liquid surface with the bubbles to form a concentrate, thereby achieving the separation of the target substance from impurities and the enrichment and concentration of the target substance) and / or solvent flotation (a small amount of solvent, i.e., flotation solvent, is covered on the flotation feed; the target substance is adsorbed on the surface of the bubbles and rises to the flotation solvent with the bubbles to form an enriched phase; based on gas adsorption separation, the selectivity of the solvent is used to further separate the target substance from impurities, while simultaneously achieving the enrichment and concentration of the target substance).

[0026] (2) Process the enriched phase / concentrate to obtain erythromycin and / or erythromycin thiocyanate, wherein the “processing” includes, but is not limited to, membrane concentration (nanofiltration or reverse osmosis), vacuum distillation, crystallization, drying and other steps and combinations thereof.

[0027] According to the method of the present invention, preferably, the carrier gas is air or nitrogen, with nitrogen being more preferred.

[0028] Preferably, the flotation is solvent flotation, and the flotation solvent can be one or a mixture of ethyl acetate, butyl acetate, n-octanol, isooctanol, n-butanol, kerosene, etc. More preferably, the height of the flotation solvent layer in the flotation column is 15mm-45mm; the volume ratio of the flotation solvent to the flotation feed is 1:10-1:20.

[0029] Preferably, the enriched phase can be recycled as a flotation solvent until the concentration of erythromycin / erythromycin thiocyanate in the enriched phase reaches 85% of its solubility.

[0030] According to the method of the present invention, the air-to-water ratio is 0.1-0.5 L / (L·min), preferably 0.2-0.3 L / (L·min); according to the method of the present invention, the flotation time is determined according to the flotation feed concentration and the flotation yield requirement, preferably 60-120 min;

[0031] According to the method described in this invention, the flotation temperature is preferably 20-30°C.

[0032] According to the method of the present invention, the pH of the flotation feed solution is preferably 8-10. The pH can be adjusted by adding acid or alkali to the flotation feed solution. Preferably, a sodium hydroxide solution of 50-100 g / L is used to adjust the pH.

[0033] According to the method of the present invention, a collector or inhibitor may be added to the flotation feed solution. Preferably, ethanol, acetone, n-octanol, isooctanol, or butyl acetate may be added, with the mass of the collector or inhibitor added per liter of flotation feed solution being approximately 0.2g-20g.

[0034] According to the method described in this invention, batch flotation or continuous flotation can be used. Preferably, continuous flotation is used, and the ratio of the continuous flotation feed flow rate to the gas flow rate is 0.02-2. More preferably, gas-liquid countercurrent continuous solvent flotation is used. More preferably, the solvent is replaced when the volume of the continuous flotation feed reaches 20-100 times the volume of the flotation solvent.

[0035] According to the method described in this invention, the flotation feed liquid can be one or more of the feed liquids or washing liquids used in the production process of erythromycin thiocyanate, such as erythromycin fermentation broth, clarified liquid after filtration of erythromycin fermentation broth, raffinate of erythromycin fermentation broth, nanofiltration permeate of erythromycin fermentation broth, mother liquor for erythromycin thiocyanate crystallization, mother liquor for recrystallization (refining crystallization) of erythromycin thiocyanate, and raffinate extracted from mother liquor for erythromycin thiocyanate crystallization. Preferably, the clarified liquid after filtration of erythromycin fermentation broth or mother liquor for recrystallization of erythromycin thiocyanate is used.

[0036] According to the method of the present invention, solid-liquid separation steps such as filtration and centrifugation can be added before flotation to remove solid impurities in the feed liquid. Among them, filtration is preferably microfiltration; centrifugation is preferably performed at a speed of 3000 r / min-4000 r / min; the centrifugation temperature is controlled at 20℃-25℃; and the centrifugation time is 5 min-10 min.

[0037] According to the method of the present invention, preferably, erythromycin / erythromycin thiocyanate product is obtained from the enriched phase by crystallization. Specifically, 0.1 to 0.5 times the volume of high-purity water is added to the enriched phase, the temperature is raised to 35 to 45°C, and the mixture is stirred. Sodium thiocyanate solution and acetic acid solution are added sequentially for crystallization. After filtration and drying, the obtained crystals are erythromycin thiocyanate. More preferably, the amount of sodium thiocyanate added is 3% to 7% of the volume of the enriched phase, and the concentration of the sodium thiocyanate solution is 200-500 g / L; the acetic acid solution is added until the pH of the solution reaches 6 to 8.

[0038] According to the method described in this invention, the flotation apparatus preferably consists of a flotation column; such as Figure 7 As shown, the flotation column is segmented, comprising a gas distributor, a collection zone, and an enrichment zone. Appropriately sized bubbles are generated in the gas distributor; these bubbles adsorb the target substance in the collection zone and rise steadily; upon reaching the enrichment zone, the bubbles burst, enriching the target substance and releasing the gas. For ease of maintenance, cleaning, and disassembly, the gas distributor, collection zone, and enrichment zone are independent of each other, sealed to each other by gaskets or sealing rings, and can be connected via flanges, etc.

[0039] According to the method of the present invention, preferably, the ratio of the diameter of the gas distributor to the inner diameter of the bottom of the collection zone is ≥0.9.

[0040] According to the method described in this invention, the main body of the collection zone is a straight cylindrical section. Preferably, the height of the straight cylindrical section of the collection zone is ≤600mm.

[0041] According to the method of the present invention, preferably, the enrichment zone is provided with a variable diameter liquid seal device, and more preferably, the bottom of the liquid seal device is connected to the collection zone with a flared structure, the angle between the flared structure and the horizontal plane is preferably 100-130°, and the ratio of the top diameter to the bottom diameter of the liquid seal device is preferably 1.15-1.50.

[0042] According to the method of the present invention, preferably, a draining component (such as a liquid sealing device in the enrichment zone) is provided at the longitudinal middle position of the liquid sealing device. Figure 8 (As shown). The drainage component is characterized by multiple small funnels (with the larger openings facing upwards and the smaller openings facing downwards) evenly distributed radially and circumferentially. The function of the drainage component is as follows: for foam flotation, the drainage component discharges the entrained flotation feed, and at the same time, the funnel structure of the drainage component reduces the gas velocity and minimizes the loss of concentrate with the gas; for solvent flotation, the drainage component discharges the entrained flotation feed, and at the same time, the funnel structure of the drainage component reduces the gas velocity and minimizes the loss of enriched phase with the gas.

[0043] According to the method of the present invention, preferably, the gas distributor uses a microporous gas distributor to disperse the carrier gas into microbubbles, and the bubble diameter is preferably 200-500 μm.

[0044] Example 1: Erythromycin was enriched from erythromycin fermentation filtrate by foam flotation and erythromycin thiocyanate product was prepared.

[0045] Take 10L of erythromycin fermentation filtrate, adjust its pH to 8.3 using 50g / L sodium hydroxide solution, add 0.5g / L sodium dodecyl sulfate (SDS) as a frother, mix thoroughly, and add to the flotation column of this invention. Figure 7 A liquid seal device is installed in the enrichment zone, and a drainage component is installed in the liquid seal device. Foam flotation uses air as the carrier gas, and a microporous gas distributor is used to control the bubble size to 250-300 μm, with an air flow ratio of 0.3 L / (L·min). The flotation temperature is 22℃, and the flotation time is 60 min. Erythromycin is adsorbed onto the bubble surface and rises with the foam layer to the top of the column to form a concentrate. After foam flotation, a concentrate volume of 1.1 L is collected. After selective adsorption by bubbles, the color of the concentrate (…) Figure 5 ) compared to fermentation broth filtrate ( Figure 4 The color of the filtrate was light. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the fermentation filtrate was 4.5 g / L, and the concentration in the concentrated filtrate was 15.5 g / L. The flotation yield of erythromycin reached 38%, and the enrichment factor reached 3.45. Further crystallization was used to prepare erythromycin thiocyanate. The crystallization process was as follows: the concentrated filtrate was heated to 35°C while stirring was started. A 500 g / L sodium thiocyanate solution was slowly added to the concentrated filtrate at a volume of 4% of the concentrated filtrate. Then, acetic acid solution was added to the concentrated filtrate until the pH reached approximately 6.2. After 30 minutes, stirring was stopped, and crystals were allowed to grow for 60 minutes before filtration. The obtained crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 78%.

[0046] Example 2: Erythromycin was enriched from erythromycin fermentation filtrate by solvent flotation and erythromycin thiocyanate product was prepared.

[0047] Take 10L of erythromycin fermentation filtrate, adjust its pH to 9.3 using a 50g / L sodium hydroxide solution, and add it to the flotation column of this invention (…). Figure 7 A liquid seal device (with a drainage component) is installed in the enrichment zone. 1L of n-octanol is added above the flotation feed as the flotation solvent. Solvent flotation uses nitrogen as the carrier gas, and a microporous gas distributor is used to control the bubble size to 300-350μm. The gas flow rate is controlled at 0.22L / (L·min), the flotation temperature is 22℃, and the flotation time is 60min. After flotation, 1L of the enriched phase is collected. The color of the enriched phase (…) Figure 6 ) compared to foam flotation concentrate ( Figure 5 The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the fermentation filtrate was 4.6 g / L, and the concentration in the enriched phase was 45.1 g / L, with a flotation yield of 98% and an enrichment factor of 9.8. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.2 times the volume of high-purity water was added to the enriched phase, and the phase was heated to 35°C while stirring was started. A 400 g / L sodium thiocyanate solution was slowly added, at a volume of 6% of the enriched phase. Then, acetic acid solution was added to the enriched phase until the pH reached approximately 6.5. Stirring was stopped after 30 minutes, and crystals were allowed to grow for 30 minutes before filtration. The resulting crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 80%.

[0048] Example 3: Erythromycin was enriched from the recrystallization mother liquor of erythromycin thiocyanate by solvent flotation and the erythromycin thiocyanate product was prepared.

[0049] Take 10 L of erythromycin thiocyanate recrystallization mother liquor, centrifuge at 4000 r / min and 25℃ for 10 min, collect the supernatant, adjust its pH to 9.7 with 100 g / L sodium hydroxide solution, and add it to the flotation column of this invention (…). Figure 7A liquid-sealed device (with a drainage component) was installed in the enrichment zone. 0.8 L of isooctanol was added as the flotation solvent above the flotation feed. Solvent flotation used air as the carrier gas, employing a microporous gas distributor to control the bubble size at 200-250 μm, with an air-to-flow ratio of 0.25 L / (L·min). The flotation temperature was 30℃, and the flotation time was 120 min. After flotation, 1.1 L of the enriched phase was collected. The color of the enriched phase was lighter than that of the foam flotation concentrate. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the recrystallization mother liquor was 6.1 g / L, and the concentration of erythromycin in the enriched phase was 54.4 g / L, achieving a flotation yield of 98% and an enrichment factor of 8.92. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.5 times the volume of high-purity water was added to the enriched phase, and the enriched phase was heated to 40°C while stirring was started. A sodium thiocyanate solution with a concentration of 500 g / L was slowly added, with the addition amount being 7% of the volume of the enriched phase. Then, acetic acid solution was added to the enriched phase until the pH value of the solution reached about 7.2. After 30 minutes, stirring was stopped, and crystals were allowed to grow for 30 minutes before filtration. The obtained crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 81%.

[0050] Example 4: Erythromycin was enriched by solvent flotation in the raffinate from the recrystallization mother liquor of erythromycin thiocyanate and the erythromycin thiocyanate product was prepared.

[0051] Take the raffinate from 10 L of erythromycin thiocyanate recrystallization mother liquor, centrifuge at 4000 r / min and 25 °C for 5 min, collect the supernatant, adjust its pH to 9 using 50 g / L sodium hydroxide solution, and add it to the flotation column of this invention (…). Figure 7 A liquid seal device (with a drainage component) is installed in the enrichment zone. 1L of a mixed solvent of isooctanol, ethyl acetate, and kerosene (isooctanol:ethyl acetate:kerosene = 60:25:15) is added above the flotation feed as the flotation solvent. Nitrogen gas is used as the carrier gas in solvent flotation. A microporous gas distributor is used to control the bubble size to 200-250μm, the gas flow rate is controlled at 0.25L / (L·min), the flotation temperature is 25℃, and the flotation time is 90min. After flotation, 1L of the enriched phase is collected. The color of the enriched phase is different from that of the foam flotation concentrate (…). Figure 5The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the raffinate of the recrystallization mother liquor was 1.7 g / L, and the concentration in the enriched phase was 16 g / L, achieving a flotation yield of 94% and an enrichment factor of 9.4. The enriched phase was recycled as the flotation solvent for subsequent flotation, and the above operation was repeated four times, resulting in an erythromycin concentration of 67 g / L in the enriched phase. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.4 times the volume of high-purity water was added to the enriched phase, and the enriched phase was heated to 35°C while stirring was started. A 400 g / L sodium thiocyanate solution was slowly added, at a volume of 5% of the enriched phase volume. Then, acetic acid solution was added to the enriched phase until the pH reached approximately 7. Stirring was stopped after 30 minutes, and crystals were allowed to grow for 30 minutes before filtration. The resulting crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 82%.

[0052] Example 5: Erythromycin was enriched from erythromycin fermentation filtrate using continuous solvent flotation and erythromycin thiocyanate product was prepared.

[0053] Take 20 L of erythromycin fermentation filtrate, adjust its pH to 8.5 using a 50 g / L sodium hydroxide solution, and continuously feed it into the flotation column of this invention at a flow rate of 5 L / h using a feed pump. Figure 7 A liquid seal device (containing a drainage component) is installed in the enrichment zone. 1L of isooctanol is added as the flotation solvent above the flotation feed, while the aqueous phase discharge rate is controlled by a valve (5L / h) to maintain stability at the two-phase interface within the column. Continuous solvent flotation uses air as the carrier gas, employing a microporous gas distributor to control the bubble size to 200-250μm, with a gas flow rate of 100L / h, a flotation temperature of 25℃, and a flotation time of 4h. After flotation, the enriched phase is collected. The color of the enriched phase is different from that of the foam flotation concentrate (…). Figure 5 The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial erythromycin concentration in the fermentation filtrate was 4.6 g / L, and the concentration in the enriched phase reached 89.2 g / L. The collected enriched phase volume was 1 L, the total feed volume was 20 L, the enriched phase volume to feed volume ratio was 1:20, the enrichment factor was 19.4, and the yield was 97%. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.4 times the volume of high-purity water was added to the enriched phase, the enriched phase was heated to 37°C, and stirring was started simultaneously. A sodium thiocyanate solution with a concentration of 400 g / L was slowly added, at a concentration of 5% of the enriched phase volume. Then, acetic acid solution was added until the solution pH reached approximately 7. Stirring was stopped after 30 minutes, crystals were allowed to grow for 30 minutes, and then filtered. The obtained crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 88%.

[0054] Example 6: Erythromycin was enriched from the raffinate of erythromycin fermentation filtrate using continuous solvent flotation and erythromycin thiocyanate product was prepared.

[0055] Take 100 L of the raffinate from the erythromycin fermentation filtrate, adjust its pH to 9 using a 50 g / L sodium hydroxide solution, and continuously feed it into the flotation column of this invention at a flow rate of 3 L / h using a feed pump. Figure 7 A liquid seal device (containing a drainage component) is installed in the enrichment zone. 1L of n-octanol is added as the flotation solvent above the flotation feed. Simultaneously, the feed discharge rate (3L / h) is controlled by a valve at the bottom of the flotation column to maintain the stability of the two-phase interface within the column. Continuous solvent flotation uses air as the carrier gas, employing a microporous gas distributor to control the bubble size to 250-300μm, with a gas flow rate of 60L / h, a flotation temperature of 27℃, and a flotation time of 33.3h. After flotation, the enriched phase is collected. The color of the enriched phase is different from that of the froth flotation concentrate (…). Figure 5 The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial erythromycin concentration in the raffinate was 0.9 g / L, and the concentration in the enriched phase reached 76.5 g / L. The collected enriched phase volume was 1 L, the total feed volume was 100 L, the enriched phase to feed volume ratio was 1:100, the enrichment factor was 85, and the yield was 85%. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.3 times the volume of high-purity water was added to the enriched phase, and the enriched phase was heated to 35°C while stirring was started. A 500 g / L sodium thiocyanate solution was slowly added, at a volume of 5% of the enriched phase volume. Then, acetic acid solution was added until the solution pH reached approximately 6.5. Stirring was stopped after 30 minutes, and crystals were allowed to grow for 30 minutes before filtration. The obtained crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 84%.

[0056] Example 7: Erythromycin was enriched from the raffinate of the recrystallization mother liquor of erythromycin thiocyanate by continuous solvent flotation and the erythromycin thiocyanate product was prepared.

[0057] Take 140 L of the raffinate from the recrystallization mother liquor of erythromycin thiocyanate, adjust its pH to 9.2 using a 50 g / L sodium hydroxide solution, and continuously feed it into the flotation column of this invention at a flow rate of 15 L / h using a feed pump. Figure 7 A liquid seal device (containing a drainage component) is installed in the enrichment zone. 2L of n-octanol is added to the top of the flotation feed as the flotation solvent. Simultaneously, the feed discharge rate (15L / h) is controlled by a valve at the bottom of the flotation column to maintain the stability of the two-phase interface within the column. Continuous solvent flotation uses air as the carrier gas, employing a microporous gas distributor to control the bubble size to 200-250μm, with a gas flow rate of 200L / h, a flotation temperature of 28℃, and a flotation time of 9.3h. After flotation, the enriched phase is collected. The color of the enriched phase is different from that of the foam flotation concentrate (…). Figure 5The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the raffinate was 1.5 g / L, while the concentration in the enriched phase reached 96.6 g / L, at which point the organic solvent needed to be replaced. The collected enriched phase volume was 2 L, the total feed volume was 140 L, the enriched phase to feed volume ratio was 1:70, the enrichment factor was 64.4, and the yield was 92%. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.5 times the volume of high-purity water was added to the enriched phase, and the enriched phase was heated to 36°C while stirring was started. A 500 g / L sodium thiocyanate solution was slowly added, at a concentration of 6% of the enriched phase volume. Then, acetic acid solution was added until the solution pH reached approximately 6.5. Stirring was stopped after 40 minutes, and crystals were allowed to grow for 30 minutes before filtration. The resulting crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 85%.

[0058] Example 8: Erythromycin was enriched from the recrystallization mother liquor of erythromycin thiocyanate by continuous solvent flotation and the erythromycin thiocyanate product was prepared.

[0059] 30 L of the recrystallization mother liquor of erythromycin thiocyanate was centrifuged at 4000 r / min and 25 °C for 5 min. The supernatant was collected, and its pH was adjusted to 10.2 using a 50 g / L sodium hydroxide solution. The supernatant was then continuously fed into the flotation column of this invention at a flow rate of 10 L / h using a feed pump. Figure 7 A liquid seal device (with a drainage component) is installed in the enrichment zone. 2L of a mixed solvent of isooctanol, n-octanol, and butyl acetate (isooctanol:n-octanol:butyl acetate = 65:25:10) is added above the flotation feed as the flotation solvent. Simultaneously, the feed discharge rate is controlled by a valve (10L / h) to maintain the stability of the two-phase interface within the column. Continuous solvent flotation uses air as the carrier gas, employing a microporous gas distributor to control the bubble size to 300-350μm, with a gas flow rate of 120L / h, a flotation temperature of 30℃, and a flotation time of 3h. After flotation, the enriched phase is collected. The color of the enriched phase is different from that of the foam flotation concentrate (…). Figure 5 The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the recrystallization mother liquor was 6.3 g / L, and the concentration of erythromycin in the enriched phase reached 89.8 g / L. The collected enriched phase volume was 2 L, the total feed volume was 30 L, the enriched phase volume to feed volume ratio was 1:15, the enrichment factor was 14.25, and the yield was 95%. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.4 times the volume of high-purity water was added to the enriched phase, the enriched phase was heated to 40°C, and stirring was started simultaneously. A 500 g / L sodium thiocyanate solution was slowly added, at a concentration of 5% of the enriched phase volume. Then, acetic acid solution was added until the solution pH was around 7.5. Stirring was stopped after 40 min, crystals were grown for 30 min, filtered, and the obtained crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 82%.

[0060] Comparative Example 1: Erythromycin was enriched from erythromycin fermentation filtrate by solvent flotation and erythromycin thiocyanate product was prepared.

[0061] Take 0.5 L of erythromycin fermentation filtrate, adjust its pH to 9 using 50 g / L sodium hydroxide solution, and add the attached... Figure 1 In the flotation column shown, 0.05 L of n-octanol was added above the flotation feed as the flotation solvent. Solvent flotation used nitrogen as the carrier gas, and a microporous gas distributor was used to control the bubble size to 250-300 μm. The gas flow rate was controlled at 0.2 L / (L·min), the flotation temperature was 25℃, and the flotation time was 60 min. After flotation, 0.05 L of the enriched phase was collected. The color of the enriched phase (…) Figure 6 ) compared to foam flotation concentrate ( Figure 5 The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the fermentation filtrate was 4.5 g / L, and the concentration in the enriched phase was 38.7 g / L, with a flotation yield of 86% and an enrichment factor of 8.6. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.3 times the volume of high-purity water was added to the enriched phase, and the phase was heated to 37°C while stirring was started. A 400 g / L sodium thiocyanate solution was slowly added, at a volume of 5% of the enriched phase volume. Then, acetic acid solution was added to the enriched phase until the pH reached approximately 6.9. Stirring was stopped after 40 minutes, and crystals were allowed to grow for 30 minutes before filtration. The resulting crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 79%.

[0062] Comparative Example 2: Erythromycin was enriched from erythromycin fermentation filtrate by solvent flotation and erythromycin thiocyanate product was prepared.

[0063] Take 10L of erythromycin fermentation filtrate, adjust its pH to 9.5 using 50g / L sodium hydroxide solution, and add it to a 10L flotation column (to remove the adsorbent). Figure 1 The flotation column shown was scaled up to 10L with the same height-to-diameter ratio. 1L of a mixed solvent of n-octanol, butyl acetate, and kerosene (n-octanol:butyl acetate:kerosene = 55:25:20) was added above the flotation feed as the flotation solvent. Air was used as the carrier gas for solvent flotation. A microporous gas distributor was used to control the bubble size to 250-350μm, the air flow rate was controlled at 0.32L / (L·min), the flotation temperature was 22℃, and the flotation time was 90min. After flotation, 0.96L of the enriched phase was collected. The color of the enriched phase was different from that of the froth flotation concentrate (…). Figure 5The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the fermentation filtrate was 4.5 g / L, and the concentration in the enriched phase was 37.5 g / L, with a flotation yield of 80% and an enrichment factor of 8.3. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.4 times the volume of high-purity water was added to the enriched phase, and the phase was heated to 37°C while stirring was started. A 400 g / L sodium thiocyanate solution was slowly added, at a volume of 5% of the enriched phase volume. Then, acetic acid solution was added to the enriched phase until the pH reached approximately 6.5. Stirring was stopped after 40 minutes, and crystals were allowed to grow for 30 minutes before filtration. The resulting crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 78%.

[0064] Comparative Example 3: Erythromycin was enriched by solvent flotation from the raffinate of the fermentation filtrate and the erythromycin thiocyanate product was prepared.

[0065] Take 10L of the raffinate from the fermentation filtrate, centrifuge at 4000 rpm and 25℃ for 5 min, collect the supernatant, adjust its pH to 9 using 50 g / L sodium hydroxide solution, and add it to a 10L flotation column (with the adsorbent...). Figure 1 In the flotation column shown (scaled up to 10L with the same height-to-diameter ratio), 1L of butyl acetate was added as the flotation solvent above the flotation feed. Solvent flotation used nitrogen as the carrier gas, with a microporous gas distributor controlling the bubble size to 200-250μm, an air flow rate of 0.25L / (L·min), a flotation temperature of 22℃, and a flotation time of 90min. After flotation, 0.9L of the enriched phase was collected. The color of the enriched phase was greater than that of the froth flotation concentrate (…). Figure 5 The color of the erythromycin was lighter. High-performance liquid chromatography (HPLC) analysis showed that the initial concentration of erythromycin in the raffinate of the fermentation filtrate was 1 g / L, and the concentration in the enriched phase was 8.4 g / L, achieving a flotation yield of 76% and an enrichment factor of 8.4. The enriched phase was recycled as the flotation solvent for subsequent flotation, and the above operation was repeated 6 times, resulting in an erythromycin concentration of 55 g / L in the enriched phase. Further crystallization yielded erythromycin thiocyanate. The crystallization process was as follows: 0.3 times the volume of high-purity water was added to the enriched phase, and the enriched phase was heated to 35°C while stirring was started. A 400 g / L sodium thiocyanate solution was slowly added, at a volume of 5% of the enriched phase volume. Then, acetic acid solution was added to the enriched phase until the pH reached approximately 6.8. Stirring was stopped after 30 minutes, and crystals were allowed to grow for 30 minutes before filtration. The resulting crystals were dried to obtain the erythromycin thiocyanate product, with a crystallization yield of 81%.

[0066] As can be seen from the above embodiments, the flotation technology of the present invention can achieve a high erythromycin recovery rate in different erythromycin thiocyanate production waste liquids, and has good stability and practicality.

[0067] In summary, this invention addresses the challenge of treating wastewater from erythromycin thiocyanate production. Based on the principle of bubble adsorption and trapping, it applies flotation technology to the recovery of erythromycin / erythromycin thiocyanate. By adjusting the flotation process parameters, highly efficient enrichment and recovery of erythromycin / erythromycin thiocyanate from the wastewater is achieved, yielding a high-yield crude erythromycin thiocyanate. This technology avoids resource waste, reduces wastewater treatment costs, and decreases organic pollutant emissions, aligning with green chemistry principles. Based on its advantages in terms of resources, environment, and economy, this invention has practical application value in the pharmaceutical industry, and is expected to promote green industrial upgrading and achieve synergistic development of ecology and economy.

[0068] The upper and lower limits of the process parameters (such as temperature, time, etc.) and the range values ​​of the present invention can all achieve the method, and examples are not listed here.

[0069] All aspects not described in detail in this invention can be covered using conventional technical knowledge in the field.

[0070] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to the embodiments, those skilled in the art should understand that modifications or equivalent substitutions to the technical solutions of the present invention do not depart from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. A method for flotation extraction of erythromycin and / or erythromycin thiocyanate, the method comprising: (1) Add the flotation feed containing erythromycin and / or erythromycin thiocyanate into the flotation column, use air or nitrogen as the carrier gas, and separate erythromycin and / or erythromycin thiocyanate by foam flotation and / or solvent flotation to obtain erythromycin and / or erythromycin thiocyanate enriched phase / concentrate. (2) Process the enriched phase / concentrate to obtain erythromycin and / or erythromycin thiocyanate.

2. The method according to claim 1, characterized in that, The flotation feed is one or more of the following: erythromycin fermentation broth, clarified liquid after filtration of erythromycin fermentation broth, raffinate of erythromycin fermentation broth, nanofiltration permeate of erythromycin fermentation broth, mother liquor of erythromycin thiocyanate crystallization, mother liquor of erythromycin thiocyanate recrystallization, and raffinate extracted from mother liquor of erythromycin thiocyanate crystallization.

3. The method according to claim 1, characterized in that, The flotation solvent for solvent flotation is a mixture of one or more solvents selected from ethyl acetate, butyl acetate, n-octanol, isooctanol, n-butanol, and kerosene.

4. The method according to claim 1, characterized in that, In solvent flotation separation, the volume ratio of flotation solvent to flotation feed is 1:10-1:

20.

5. The method according to claim 1, characterized in that, The pH of the flotation feed solution is 8-10, the flotation temperature is 20-30℃, and the flotation time is 60-120 min.

6. The method according to claim 1, characterized in that, In flotation separation, the carrier gas flow rate is 0.1-0.5 L / (L·min).

7. The method according to claim 1, characterized in that, The flotation can be batch flotation or continuous flotation; when continuous flotation is used, the ratio of the feed liquid flow rate to the carrier gas flow rate is 0.02-2.

8. The method according to claim 1, characterized in that, The enriched phase is recycled as a flotation solvent until the concentration of erythromycin and / or erythromycin thiocyanate in the enriched phase reaches 85% of its solubility.

9. A flotation column for flotation extraction of erythromycin and / or erythromycin thiocyanate, characterized in that, The flotation column adopts a segmented design, comprising a gas distributor, a collection zone, and an enrichment zone. The gas distributor, collection zone, and enrichment zone are independent of each other, and are sealed to each other by gaskets or sealing rings and connected by flanges.

10. The flotation column according to claim 9, characterized in that, A variable-diameter liquid seal device is installed in the enrichment zone. The bottom of the liquid seal device is connected to the collection zone with a flared structure. The angle between the flared structure and the horizontal plane is 100-130°. The ratio of the diameter of the top to the bottom of the liquid seal device is 1.15-1.50.

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