Extraction method of Feramectin sulfate
By employing a two-stage purification method, using a series of cationic resin columns, weakly positive resin columns, and anionic resin columns, combined with washing and elution steps with low, medium, and high concentrations of ammonia water, the problem of separating and purifying flamectin sulfate was solved, achieving high-purity, high-yield, and low-cost production of flamectin sulfate.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- YICHANG SANXIA PHARM CO LTD
- Filing Date
- 2026-03-06
- Publication Date
- 2026-05-12
AI Technical Summary
Existing technologies are difficult to efficiently separate and purify flamecone sulfate, leading to a contradiction between high purity and high yield, as well as high cost and serious pollution.
A two-stage purification method was adopted, using a series of cationic resin columns, weakly positive resin columns, and anionic resin columns, combined with washing and elution steps with low, medium, and high concentrations of ammonia water, to optimize the separation and reduce the amount of ammonia water used.
It significantly improved the purity and yield of flamecone sulfate, reduced production costs, decreased environmental pollution, and shortened the production cycle.
Smart Images
Figure SMS_1
Abstract
Description
Technical Field
[0001] This invention belongs to the field of pharmaceutical raw material preparation technology, specifically relating to a method for extracting flamecoxib sulfate. Background Technology
[0002] Furamectin sulfate, also known as neomycin B sulfate, is an aminoglycoside antibiotic isolated from neomycin sulfate. It exhibits good antibacterial activity against Staphylococcus aureus, Corynebacterium, Escherichia coli, Klebsiella, and Proteus. Furamectin sulfate has 1.3 times the antibacterial activity of neomycin sulfate and overcomes its side effects. It can be formulated into injections, powders, and ointments for use.
[0003] Currently, the commonly used method for preparing flamectin sulfate involves separation from the fermentation broth of neomycin sulfate. However, this fermentation broth contains neomycin B phosphate, neomycin C sulfate, and other impurities. Neomycin C sulfate accounts for 15-18% of the broth, but it has almost no antibacterial activity and is 300 times more toxic than neomycin B sulfate. Therefore, to obtain high-purity, low-toxicity flamectin sulfate, the content of neomycin C sulfate needs to be minimized. However, neomycin B and C are stereoisomers with very similar physicochemical properties such as polarity, molecular weight, and solubility, making them difficult to separate effectively using conventional methods (such as precipitation and simple extraction). Furthermore, the fermentation broth contains impurities such as neomycin amine, degradation products, proteins, and pigments. Some of these impurities exhibit similar adsorption / desorption behavior to the target analyte, leading to co-elution and lengthy purification steps. Repeated purification can result in loss of the target analyte, further reducing the yield and creating a "purity-yield" contradiction.
[0004] Chinese patent CN108976263A discloses a method for purifying flamectin sulfate. The method involves dissolving crude flamectin sulfate in water, adsorbing it through an ion exchange resin column, pre-washing with low-concentration ammonia (0.25-0.35%), further pre-washing with high-concentration ammonia (0.4-0.6%), and then eluting the ammonia solution to obtain an eluent. This eluent is then concentrated, salted, decolorized, and spray-dried to obtain flamectin sulfate. This invention can produce flamectin sulfate with a purity >98%, increasing the yield by 20-25% compared to existing processes. It has the advantages of low preparation cost, high quality, and ease of implementation. However, this invention uses a weakly positive resin for single adsorption, which is highly dependent on the quality of the starting material and results in relatively high costs.
[0005] Chinese patent CN101343295B discloses a method for extracting flamectin sulfate from neomycin sulfate fermentation broth. The method involves adsorbing, desorbing, and concentrating the neomycin sulfate fermentation broth using a strongly acidic ion exchange resin. The concentrated liquid is then adsorbed using a weakly acidic cation exchange resin, followed by elution with 0.1-1.0M ammonia water. Finally, the flamectin sulfate is obtained through concentration, acidification, decolorization, spray drying, and micronization. This method improves resin adsorption selectivity, reduces the amount of eluent used, and eliminates organic solvent residue, reducing environmental pollution and improving yield and product quality. However, this method primarily uses the same low-concentration ammonia water for washing and impurity removal, resulting in a long processing time, high ammonia waste, and low yield.
[0006] Therefore, it is necessary to develop a low-cost, low-pollution method that can improve product purity and yield for the production of framectin sulfate. Summary of the Invention
[0007] To address the aforementioned technical problems, this invention provides a method for extracting framycin sulfate, which uses a two-stage purification process to obtain high-purity framycin sulfate, while reducing the amount of ammonia used and lowering costs.
[0008] To achieve the above objectives, the present invention provides a method for extracting flammacin sulfate, comprising the following steps:
[0009] (1) The neomycin fermentation broth was passed into the adsorption system for adsorption, washing and elution. The volume of the elution was concentrated to 45-52% at the end of the elution to obtain the elution concentrate. (2) Dilute the concentrated solution and pass it through the first positive resin for complete dynamic adsorption; (3) The first ammonia solution is passed into the first positive resin for washing; (4) After washing, the second positive resin and the anion resin are connected in series and washed with the second ammonia water. Then, the analytical reagent is introduced for analysis and the analytical solution is collected. (5) The eluent was concentrated, decolorized by salting, and spray-dried to obtain framectin sulfate.
[0010] Preferably, the optical rotation titer of the analytical concentrate in step (1) is 200,000-300,000 U / mL.
[0011] Preferably, the adsorption system described in step (1) consists of multiple cation exchange resins and anion exchange resins connected in series.
[0012] Preferably, the optical rotation titer of the diluted analytical concentrate in step (2) is 30,000-50,000 U / mL.
[0013] Preferably, the first positive resin in step (2) is 732 cationic resin.
[0014] Preferably, the second positive resin in step (4) is LX-55 weak positive resin or D152 weak positive resin; the anion resin is 700 anion resin.
[0015] Preferably, the concentration of the first ammonia solution in step (3) is 0.1-0.2 mol / L, the flow rate is 0.2-0.8 BV / h, and the total amount used is 10-16 BV.
[0016] Preferably, the concentration of the second ammonia solution in step (4) is 0.3-0.5 mol / L, the flow rate is 0.1-0.2 BV / h, and the total amount used is 12-18 BV.
[0017] Preferably, the analytical reagent in step (4) is a 2.5-3.0 mol / L ammonia solution, with a flow rate of 0.1-0.2 BV / h and a total amount of 10-12 BV.
[0018] Preferably, the optical rotation titer of the eluent in step (4) is 3000-8000 U / mL.
[0019] Preferably, the salt conversion method described in step (5) involves adding sulfuric acid solution to adjust the pH.
[0020] More preferably, the concentration of the sulfuric acid solution is 5-8 mol / L; and the pH value after pH adjustment is 7-8.
[0021] The beneficial effects of this invention are as follows: This invention directly extracts flamabrine sulfate from neomycin fermentation broth and directly purifies it to high purity, breaking the vicious cycle of "yield-purity" in traditional processes and offering significant breakthroughs in cost control and quality uniformity. It also reduces reliance on high-quality raw materials, minimizes losses in intermediate steps, and avoids activity loss due to impurity encapsulation, thereby increasing the overall yield. Furthermore, it saves production costs, achieves more precise impurity separation, greatly improves product purity and safety, and shortens the production cycle.
[0022] This invention employs a two-stage purification method, using a cation exchange resin column, a weakly positive resin column, and an anion exchange resin column for continuous processing. The weakly positive resin can simultaneously elute and adsorb, and its smaller particle size increases the number of separation plates, further improving the separation degree of the isomers neomycin C and neomycin B, and significantly improving the purity of framectin sulfate.
[0023] This invention first uses a low-concentration ammonia solution for washing, then a medium-concentration ammonia solution, and finally a high-concentration ammonia solution for a single wash. This achieves better separation and saves on ammonia usage and washing time, significantly reducing the production of waste ammonia and thus alleviating wastewater treatment pressure. Furthermore, since ammonia solution is used throughout the process, the final product contains no organic solvent residue, improving product safety and reducing environmental pollution. Detailed Implementation
[0024] The technical solution of the present invention will be further explained and described below with reference to specific embodiments. It is worth noting that the following embodiments are only preferred embodiments of the present invention and should not be construed as limiting the present invention. The scope of protection of the present invention should be determined by the contents of the claims. Modifications and substitutions made by those skilled in the art to the technical solution of the present invention without creative effort all fall within the scope of protection of the present invention.
[0025] In the following examples, the neomycin fermentation broth was provided by Yichang Three Gorges Pharmaceutical Co., Ltd., and was obtained by fermentation with Streptomyces freundii strain for 125-155 hours; 732 cationic resin: purchased from Wandong High-Tech (Tianchang) Co., Ltd., with a pore size of 0.5-1.1 nm; LX-55 weakly positive resin: purchased from Xi'an Lanxiao Technology New Material Co., Ltd., with a pore size of 0.2-0.6nm. Before being connected to the analytical system, it was treated with 1.0-1.3M hydrochloric acid for 3-4 BV, and then washed with water for 3-4 BV before use. D152 weak positive resin: purchased from Tianjin Yunkai Resin Technology Co., Ltd., with a pore size of 0.3-1.25nm. Before being connected to the analytical system, it was treated with 1.0-1.3M hydrochloric acid for 3-4 BV and then washed with water for 3-4 BV before use. 700 anion exchange resin: purchased from Gaoling Lanxiao Technology New Materials Co., Ltd., with a pore size of 0.3-1.25nm. Before being connected to the system, the resin was treated with 1.0-1.5M sodium hydroxide solution for 3-4bV, washed with water, then treated with 1.0-1.3M hydrochloric acid for 3-4bV, and then washed with water for 3-4bV before use.
[0026] Example 1 (1) Adjust the pH of the neomycin fermentation broth to 6.5, add 732 resin to the fermentation broth for adsorption for 6-8 hours, and after sieving the resin, take the saturated resin and pack it into three 732 cationic resin columns. (2) Three saturated resins were sequentially passed through tap water for 2 bv, detergent (prepared from 0.12 mol / L hydrochloric acid and 0.4 mol / L ammonium chloride) for 5 bv, and then washed with water for 2 bv at a rate of 1 BV / h. (3) A 700-column filter was connected in series and 0.15 mol / L ammonia was passed through for washing. The total washing volume was 5 BV. After washing, 2.4 mol / L ammonia was passed through at a rate of 0.1 BV / h for analysis. The analytical solution with an optical rotation value of 50,000 U / mL was collected. Then the analytical solution was concentrated to an optical rotation value of 200,000 U / mL and a total volume of 80% of the resin saturation to obtain the analytical solution concentrate. (4) Dilute the concentrated solution to 35,000 U / mL, and then pass it through an empty 732 cation exchange resin column at a flow rate of 0.5 BV / h. After complete adsorption, wash with water at a flow rate of 1 BV / h for 1 h; then wash with 0.11 mol / L ammonia solution at a flow rate of 0.2 BV / h, with a total washing volume of 15 BV. (5) Connect an LX-55 weak positive resin column and a 700 anion resin column in series after the 732 cation resin column, and then pass a 0.42 mol / L ammonia solution through the 732 cation resin column at a flow rate of 0.2 BV / h for secondary washing. (6) The optical rotation titer was measured by sampling at the outlet of the 700 anion exchange resin column. When the optical rotation titer reached a peak of 8067 U / mL, it began to decrease. After 6 hours, a 2.50 mol / L ammonia solution was introduced into the 732 cation exchange resin column at a flow rate of 0.15 BV / h for rapid analysis. When the optical rotation titer rose again to above 8000 U / mL, the eluent was collected from the outlet of the 700 anion exchange resin column. The collection was stopped when the optical rotation titer was 3000 U / mL. (7) The eluent was concentrated to an optical rotation potency of 250,000 U / mL, then the pH was adjusted to 7 using a 6 mol / L concentrated sulfuric acid solution for salt conversion, followed by decolorization with activated carbon, and finally spray-dried to obtain flammacin sulfate product; wherein the amount of activated carbon used was 0.05 kg / 10 9 u.
[0027] Example 2 (1) The pH of the neomycin fermentation broth was adjusted to 6.8, and 732 resin was added to the fermentation broth for adsorption for 8 hours. After the resin was sieved, the saturated resin was loaded into three 732 cationic resin columns. (2) Three saturated resins were sequentially passed through tap water for 2 bv, detergent (prepared from 0.15 mol / L hydrochloric acid and 0.4 mol / L ammonium chloride) for 5 bv, and then washed with water for 2 bv at a rate of 1 BV / h. (3) A 700-column filter was connected in series and 0.15 mol / L ammonia was passed through for washing. The total washing volume was 5 BV. After washing, 2.6 mol / L ammonia was passed through at a rate of 0.2 BV / h for analysis. The analytical solution with an optical rotation value of 80,000 U / mL was collected. Then the analytical solution was concentrated to an optical rotation value of 200,000 U / mL and a total volume of 85% of the resin saturation to obtain the analytical solution concentrate. (4) Dilute the concentrated solution to 39,000 U / mL, and then pass it through an empty 732 cation exchange resin column at a flow rate of 0.5 BV / h. After complete adsorption, wash with water at a flow rate of 1 BV / h for 1 h; then wash with 0.18 mol / L ammonia solution at a flow rate of 0.2 BV / h, with a total washing volume of 13 BV. (5) Connect an LX-55 weak positive resin column and a 700 anion resin column in series after the 732 cation resin column, and then pass a 0.35 mol / L ammonia solution through the 732 cation resin column at a flow rate of 0.2 BV / h for secondary washing. (6) The optical rotation titer was measured at the outlet of the 700 column. When the optical rotation titer at the outlet of the 700 anion exchange resin column reached a peak value of 1953 U / mL, it began to decrease. After 6 hours, a 2.52 mol / L ammonia solution was introduced into the 732 cation exchange resin column at a flow rate of 0.15 BV / h for rapid analysis. When the optical rotation titer rose again to above 8000 U / mL, the eluent was collected from the outlet of the 700 anion exchange resin column. The collection was stopped when the optical rotation titer was 3000 U / mL. The eluent was obtained. (7) The eluent was concentrated to an optical rotation potency of 230,000 U / mL, then the pH was adjusted to 7.5 using 6 mol / L concentrated sulfuric acid solution for salt conversion, followed by decolorization with activated carbon, and finally spray-dried to obtain flammacin sulfate product; wherein the amount of activated carbon used was 0.05 kg / 10 9 u.
[0028] Example 3 (1) The pH of the neomycin fermentation broth was adjusted to 6.6. 732 resin was added to the fermentation broth for adsorption for 7 hours. After the resin was screened, the saturated resin was loaded into three 732 cation exchange resin columns. (2) Three saturated resins were sequentially passed through tap water for 2 bv, detergent (prepared with 0.14 mol / L hydrochloric acid and 0.4 mol / L ammonium chloride) for 5 bv, and then washed with water for 2 bv at a rate of 1 BV / h. (3) A 700-column filter was connected in series and 0.15 mol / L ammonia was passed through for washing. The total washing volume was 5 BV. After washing, 2.5 mol / L ammonia was passed through at a rate of 0.15 BV / h for analysis. The analytical solution with an optical rotation value of 36,000 U / mL was collected. Then the analytical solution was concentrated to an optical rotation value of 200,000 U / mL and a total volume of 83% of the resin saturation to obtain the analytical solution concentrate. (4) The concentrated solution was passed through an empty 732 cation exchange resin column at a flow rate of 0.5 BV / h. After complete adsorption, it was washed with water at a flow rate of 1 BV / h for 1 h. Then, 0.19 mol / L ammonia solution was passed through the column at a flow rate of 0.2 BV / h for washing. The total washing volume was 10 BV. (5) Connect an LX-55 weak positive resin column and a 700 anion resin column in series after the 732 cation resin column, and then pass a 0.5 mol / L ammonia solution through the 732 cation resin column at a flow rate of 0.2 BV / h for secondary washing. (6) The optical rotation titer was measured at the outlet of the 700 column. When the optical rotation titer at the outlet of the 700 anion exchange resin column reached a peak value of 2301 U / mL, it began to decrease. After 6 hours, 2.55 mol / L ammonia solution was introduced into the 732 cation exchange resin column at a flow rate of 0.15 BV / h for rapid analysis. When the optical rotation titer reached above 8000 U / mL again, the eluent was collected from the outlet of the 700 anion exchange resin column. The collection was stopped when the optical rotation titer was 3000 U / mL. The eluent was obtained. (7) The eluent was concentrated to an optical rotation potency of 260,000 U / mL, then the pH was adjusted to 7 using a 6 mol / L concentrated sulfuric acid solution for salt conversion, followed by decolorization with activated carbon, and finally spray-dried to obtain flammacin sulfate product; wherein the amount of activated carbon used was 0.05 kg / 10 9 u.
[0029] Example 4 (1) The pH of the neomycin fermentation broth was adjusted to 6.7, and 732 resin was added to the fermentation broth for adsorption for 6.5 hours. After the resin was sieved, the saturated resin was loaded into three 732 cation exchange resin columns. (2) Three saturated resins were sequentially passed through tap water for 2 bv, detergent (prepared from 0.13 mol / L hydrochloric acid and 0.4 mol / L ammonium chloride) for 5 bv, and then washed with water for 2 bv at a rate of 1 BV / h. (3) A 700-column filter was connected in series and 0.15 mol / L ammonia was passed through for washing. The total washing volume was 5 BV. After washing, 2.5 mol / L ammonia was passed through at a rate of 0.1 BV / h for analysis. The analytical solution with an optical rotation value of 50,000 U / mL was collected. Then the analytical solution was concentrated to an optical rotation value of 200,000 U / mL and a total volume of 80% of the resin saturation to obtain the analytical solution concentrate. (4) Dilute the concentrated solution to 45,000 U / mL, and then pass it through an empty 732 cation exchange resin column at a flow rate of 0.5 BV / h. After complete adsorption, wash with water at a flow rate of 1 BV / h for 1 h; then wash with 0.11 mol / L ammonia solution at a flow rate of 0.2 BV / h, with a total washing volume of 15 BV. (5) A D152 weak positive resin column and a 700 anion resin column are connected in series after the 732 cation resin column. Then, a 0.3 mol / L ammonia solution is passed through the 732 cation resin column at a flow rate of 0.2 BV / h for secondary washing. (6) The optical rotation titer was measured at the outlet of the 700 column. When the optical rotation titer at the outlet of the 700 anion exchange resin column reached a peak of 2500 U / mL, it began to decrease. After 6 hours, a 2.54 mol / L ammonia solution was introduced into the 732 cation exchange resin column at a flow rate of 0.15 BV / h for rapid analysis. When the optical rotation titer reached above 8000 U / mL again, the eluent was collected from the outlet of the 700 anion exchange resin column. The collection was stopped when the optical rotation titer was 3000 U / mL. The eluent was obtained. (7) The eluent was concentrated to an optical rotation potency of 250,000 U / mL, then the pH was adjusted to 8 using a 6 mol / L concentrated sulfuric acid solution for salt conversion, followed by decolorization with activated carbon, and finally spray-dried to obtain framectin sulfate product; wherein the amount of activated carbon used was 0.05 kg / 10 9 u.
[0030] Comparative Example 1 The method and steps are the same as in Example 1, except that in step (5), the LX-55 weak positive resin column is not connected in series, but only a 700 anion resin column is connected in series, and ultimately a qualified flamecone sulfate product cannot be prepared.
[0031] Comparative Example 2 The method and steps are the same as in Example 1, except that step (5) is omitted. A 0.42 mol / L ammonia solution is directly introduced into the 732 cation exchange resin column at a flow rate of 0.2 BV / h for secondary washing, with a total washing volume of 14 BV. When the optical rotation titer at the outlet of the 732 cation exchange resin column is below 3000, a 2.5 mol / L ammonia solution is used to precipitate the solution at a flow rate of 0.15 BV / h. When the optical rotation titer is higher than 8000 U / mL, the eluent is collected from the outlet of the 732 cation exchange resin column, and collection is stopped when the optical rotation titer is 3000 U / mL. The eluent is then obtained. Finally, the product is prepared by salt decolorization and spray drying. However, it is ultimately impossible to obtain a qualified framectin sulfate product.
[0032] Comparative Example 3 The method and steps are the same as in Example 1, except that in step (5), a 0.11 mol / L ammonia solution is passed through at a flow rate of 0.2 BV / h for washing until the outlet optical rotation titer reaches below 800 u / mL. Then, a 2.5 mol / L ammonia solution is used to elute the column in a 732 cation exchange resin column at a flow rate of 0.1 BV / h. When the optical rotation titer is higher than 8000 U / mL, the eluent is collected from the outlet of the 700 anion exchange resin column. When the optical rotation titer is lower than 3000 U / mL, the collection is stopped, and the eluent is obtained. The finished product is prepared by salt decolorization and spray drying. In the end, it is impossible to obtain a qualified framectin sulfate product.
[0033] Comparative Example 4 (1)-(4): Same as Example 1; (5) Connect the blank 732 resin column and the 700 anion resin column in series. 0.11 mol / L ammonia solution is introduced into the first 732 cation resin column at a flow rate of 0.2 BV / h for washing. When the optical rotation titer at the outlet reaches 7023 U / mL, it begins to decrease. 2.5 mol / L ammonia solution is used in the 732 cation resin column at a flow rate of 0.15 BV / h for analysis. When the optical rotation titer is higher than 8000 U / mL, the eluent is collected from the outlet of the 700 anion resin column. When the optical rotation titer is lower than 3000 U / mL, the collection is stopped to obtain the eluent. (6) The eluent was concentrated to an optical rotation potency of 250,000 U / mL, and then the pH was adjusted to 7 using a 6 mol / L concentrated sulfuric acid solution for salt conversion. Then activated carbon was added for decolorization, and the finished product was obtained by spray drying. Finally, it was impossible to obtain a qualified flammacin sulfate product.
[0034] Comparative Example 5 (1)-(3): Same as Example 1; (4) Dilute the concentrated solution to 35,000 U / mL, the total amount being 85% of the resin saturation, and then pass it into the LX-55 weak positive resin column at a flow rate of 0.5 BV / h. After complete adsorption, wash with 0.11 mol / L ammonia solution at a flow rate of 0.2 BV / h, the total washing amount being 15 BV. (5) Only one 700 anion exchange resin column is connected in series after the LX-55 weak positive resin column, and then a 0.43 mol / L ammonia solution is passed through at a flow rate of 0.2 BV / h for secondary washing, wherein the total washing volume is 15 BV; (6) The optical rotation titer was measured at the outlet of the 700 column. When the optical rotation titer at the outlet of the 700 anion exchange resin column reached a peak of 9200 U / mL, it began to decrease. After 6 hours, a 2.49 mol / L ammonia solution was introduced into the 732 cation exchange resin column at a flow rate of 0.15 BV / h for rapid analysis. When the optical rotation titer rose again to above 8000 U / mL, the eluent was collected from the outlet of the 700 anion exchange resin column. The collection was stopped when the optical rotation titer was 3000 U / mL. The eluent was obtained. (7) The eluent was concentrated to an optical rotation titer of 255,000 U / mL, and then the pH was adjusted to 7 using a 6 mol / L concentrated sulfuric acid solution for salt conversion. Then, 0.05 kg / billion activated carbon was added for decolorization. Finally, the product was obtained by spray drying. In the end, it was impossible to prepare a qualified framectin sulfate product.
[0035] Table 1 Performance Indicators of Flamabestin Sulfate
[0036] The results showed that in Examples 1-4, the 732 cation exchange resin column, LX-55 weak positive resin and 700 anion exchange resin were used in series to adsorb, wash and decompose the concentrated solution of neomycin fermentation broth, and finally obtained framectin sulfate product with a dry product potency of 730 U / mg and a neomycin C impurity content of ≤2.1%, achieving a synergistic improvement in yield and purity. In Comparative Example 1, using only 700 resin without LX-55 resin and with the same subsequent washing process, a qualified flamectin sulfate sample could not be obtained. In Comparative Example 2, using neither LX-55 nor 700 resin, a qualified flamectin sulfate sample could not be obtained. In Comparative Example 3, using only low-concentration ammonia for continuous washing without medium-concentration ammonia, a qualified flamectin sulfate sample could not be obtained. In Comparative Example 4, using empty 732 resin instead of LX-55 resin, a qualified flamectin sulfate sample could not be obtained. In Comparative Example 5, using LX-55 resin instead of 732 resin for secondary adsorption, omitting the washing-adsorption process, a qualified flamectin sulfate sample still could not be obtained. These comparative results show that the weakly positively charged LX-55 and D152 resins play an important role in the preparation of flamectin. Furthermore, the simultaneous washing and adsorption of empty acidic LX-55 and D152 resins with medium-concentration ammonia plays a crucial role in the removal and separation of impurities.
Claims
1. A method for extracting framycin sulfate, characterized in that: Includes the following steps: (1) The neomycin fermentation broth is passed into the adsorption system for adsorption, washing and elution. The volume of the elution solution at the end of the system is concentrated to obtain the elution concentrate. (2) Dilute the concentrated solution and pass it through the first positive resin for complete dynamic adsorption; (3) The first ammonia solution is passed into the first positive resin for washing; (4) After washing, the second positive resin and the anion resin are connected in series, and the second ammonia water is passed through for washing. Then the analytical reagent is passed through for analysis, and the analytical solution is collected. (5) The eluent was concentrated, decolorized by salting, and spray-dried to obtain framectin sulfate.
2. The method for extracting framycin sulfate according to claim 1, characterized in that: The optical rotation titer of the analytical concentrate described in step (1) is 200,000-300,000 U / mL.
3. The method for extracting framycin sulfate according to claim 1, characterized in that: The adsorption system described in step (1) consists of multiple cation exchange resins and anion exchange resins connected in series.
4. The method for extracting framycin sulfate according to claim 1, characterized in that: The optical rotation titer of the diluted analytical concentrate described in step (2) is 30,000-50,000 U / mL.
5. The method for extracting framycin sulfate according to claim 1, characterized in that: The first positive resin in step (2) is 732 cationic resin; the second positive resin in step (4) is LX-55 weak positive resin or D152 weak positive resin; the anionic resin is 700 anionic resin.
6. The method for extracting framycin sulfate according to claim 1, characterized in that: The concentration of the first ammonia solution in step (3) is 0.1-0.2 mol / L, the flow rate is 0.2-0.8 BV / h, and the total amount used is 10-16 BV; the concentration of the second ammonia solution in step (4) is 0.3-0.5 mol / L, the flow rate is 0.1-0.2 BV / h, and the total amount used is 12-18 BV.
7. The method for extracting framycin sulfate according to claim 1, characterized in that: The analytical reagent in step (4) is a 2.5-3.0 mol / L ammonia solution with a flow rate of 0.1-0.2 BV / h and a total amount of 10-12 BV.
8. The method for extracting framycin sulfate according to claim 1, characterized in that: The optical rotation titer of the eluent in step (4) is 3000-8000 U / mL.
9. The method for extracting framycin sulfate according to claim 1, characterized in that: The method for salt conversion described in step (5) involves adding sulfuric acid solution to adjust the pH.
10. The method for extracting framycin sulfate according to claim 9, characterized in that: The concentration of the sulfuric acid solution is 5-8 mol / L; the pH value after pH adjustment is 7-8.