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CN-122011054-A - Extraction method of framectin sulfate

CN122011054ACN 122011054 ACN122011054 ACN 122011054ACN-122011054-A

Abstract

The invention discloses an extraction method of framectin sulfate, which comprises the steps of adsorbing, washing and analyzing neomycin fermentation liquor through an adsorption system, concentrating to obtain analysis concentrated liquor, dynamically adsorbing the analysis concentrated liquor to cation resin after dilution, connecting weak positive resin and anion resin in series after washing with low-concentration ammonia water, analyzing high-concentration ammonia water after washing with medium-concentration ammonia water, concentrating, converting salt to decolor, and spray drying to obtain framectin sulfate. The invention adopts the thought of breaking through the conventional resin primary adsorption and gradient washing, adopts the resin with weak positive and low particle diameter to carry out secondary dynamic adsorption and analysis, realizes better separation degree, reduces the production cost and prepares the high-purity framomycin sulfate.

Inventors

  • XIANG JIWU
  • DING QIANG
  • TAN XIAOFANG
  • XIE FEI
  • DENG QIANG
  • HU YAN
  • ZOU YUE

Assignees

  • 宜昌三峡制药有限公司

Dates

Publication Date
20260512
Application Date
20260306

Claims (10)

  1. 1. The extraction method of the framectin sulfate is characterized by comprising the following steps of: (1) Introducing neomycin fermentation liquor into an adsorption system, adsorbing, washing and resolving, and concentrating 45-52% of the volume of the rear end of the resolved liquor to obtain resolved concentrated liquor; (2) Diluting the analysis concentrated solution, and introducing the first positive resin for dynamic adsorption completely; (3) Introducing first ammonia water into the first positive resin for washing; (4) After the washing is finished, the second positive resin and the negative resin are connected in series, and are washed by introducing second ammonia water, then are analyzed by introducing an analysis reagent, and the analysis liquid is collected; (5) Concentrating the resolved solution, decolorizing with salt, and spray drying to obtain framectin sulfate.
  2. 2. The method for extracting framycins sulfate according to claim 1, wherein the analytical concentrate in the step (1) has an optical titer of 20-30 ten thousand U/mL.
  3. 3. The method for extracting framectin sulfate according to claim 1, wherein the adsorption system in the step (1) is formed by connecting a plurality of cationic resins and anionic resins in series.
  4. 4. The method for extracting framycins sulfate according to claim 1, wherein the optical titer of the diluted analytical concentrate in the step (2) is 3-5 ten thousand U/mL.
  5. 5. The method for extracting framectin sulfate according to claim 1, wherein the first positive resin in the step (2) is 732 cationic resin, the second positive resin in the step (4) is LX-55 weak positive resin or D152 weak positive resin, and the negative resin is 700 anionic resin.
  6. 6. The method for extracting framectin sulfate according to claim 1, wherein the concentration of the first ammonia water in the step (3) is 0.1-0.2mol/L, the flow rate is 0.2-0.8BV/h, the total consumption is 10-16BV, the concentration of the second ammonia water in the step (4) is 0.3-0.5 mol/L, the flow rate is 0.1-0.2BV/h, and the total consumption is 12-18BV.
  7. 7. The method for extracting framectin sulfate according to claim 1, wherein the resolving agent in the step (4) is 2.5-3.0 mol/L ammonia water solution, the flow rate is 0.1-0.2BV/h, and the total consumption is 10-12BV.
  8. 8. The method for extracting framectin sulfate according to claim 1, wherein the optical titer of the analytical solution obtained in the step (4) is 3000-8000U/mL.
  9. 9. The method for extracting framectin sulfate according to claim 1, wherein the salt transferring method in the step (5) is to add sulfuric acid solution to adjust the pH.
  10. 10. The method for extracting framectin sulfate according to claim 9, wherein the concentration of the sulfuric acid solution is 5-8mol/L, and the pH value after the pH adjustment is 7-8.

Description

Extraction method of framectin sulfate Technical Field The invention belongs to the technical field of preparation of medicine raw materials, and particularly relates to an extraction method of framectin sulfate. Background The framycetin sulfate, also called neomycin B sulfate, is an aminoglycoside antibiotic separated and extracted from neomycin sulfate, and has good antibacterial effect on staphylococcus aureus, corynebacteria, escherichia coli, klebsiella, proteus and the like. The antibacterial activity of the framycetin sulfate is 1.3 times that of neomycin sulfate, and the framycetin sulfate overcomes the side effect of neomycin sulfate, and can be prepared into injection, powder and ointment. The preparation method of the framycins is commonly used at present, the framycins are separated from neomycin sulfate fermentation liquor, but the neomycin sulfate fermentation liquor contains neomycin phosphate B, neomycin sulfate C and other impurities, wherein the neomycin sulfate C contains 15-18% of neomycin sulfate, but the framycins have almost no antibacterial activity and toxicity which is 300 times that of the neomycin sulfate B, so that the framycins with high purity and low toxicity are required to be prepared, and the content of the neomycin sulfate C needs to be reduced as much as possible. However, neomycin B and neomycin C are stereoisomers, the physical and chemical properties of polarity, molecular weight, solubility and the like are very close, and the conventional separation means (such as precipitation and simple extraction) are difficult to effectively split. Meanwhile, the impurities such as the Xinmycin amine, degradation products, proteins, pigments and the like contained in the fermentation liquor have similar adsorption/desorption behaviors with the target substances, are easy to co-elute, lead to lengthy purification steps, lead to the loss of the target substances due to repeated purification, further reduce the yield and form the contradiction of purity-yield. Chinese patent CN108976263a discloses a method for purifying framectin sulfate, which comprises dissolving framectin sulfate crude product in water, adsorbing with ion exchange resin column, pre-washing with low concentration ammonia water (0.25-0.35%), pre-washing with high concentration ammonia water (0.4-0.6%), resolving ammonia water to obtain resolved solution, concentrating, salifying, decolorizing, and spray drying to obtain framectin sulfate. The invention can expand the framectin sulfate with purity of more than 98 percent, improves the yield by 20 to 25 percent compared with the prior art, and has the advantages of low preparation cost, good quality and easy realization. However, the invention uses a weak positive resin for one-time adsorption, has high dependence on the high quality of the starting materials and has relatively high cost. Chinese patent CN101343295B discloses a method for extracting framectin sulfate from neomycin sulfate fermentation liquor, which comprises the steps of adsorbing, resolving and concentrating the neomycin sulfate fermentation liquor through strong acid ion resin, then adsorbing the concentrated liquor through weak acid cation exchange resin, eluting with 0.1-1.0M ammonia water, and finally concentrating, acidifying, decolorizing, spray drying and micronizing to obtain framectin sulfate, wherein the framectin sulfate has the advantages of improving the adsorption selectivity of the resin, reducing the using amount of eluent, simultaneously, no organic solvent residue in the product, reducing the environmental pollution and improving the yield and the product quality. However, the method mainly adopts the same low-concentration ammonia water for washing and removing impurities, and has the advantages of long time consumption, more waste ammonia water generation and low yield. Thus, there is a need to develop a process for producing framectin sulfate which is low in cost, less in pollution and capable of improving the purity and yield of the product. Disclosure of Invention Aiming at the technical problems, the invention provides the extraction method of the framectin sulfate, which adopts secondary purification to prepare the high-purity framectin sulfate, reduces the consumption of ammonia water and reduces the cost. In order to achieve the above object, the present invention provides a method for extracting framectin sulfate, comprising the steps of: (1) Introducing neomycin fermentation liquor into an adsorption system for adsorption, washing and analysis, and concentrating 45-52% by volume of the rear end of the analysis liquor to obtain analysis concentrate; (2) Diluting the analysis concentrated solution, and introducing the first positive resin for dynamic adsorption completely; (3) Introducing first ammonia water into the first positive resin for washing; (4) After the washing is finished, the second positive resin and the negative resin are connected in series, and are washe