Method for producing aseptic bulk drug tylosin salt by utilizing tylosin fermentation broth

A technology of tylosin and fermentation broth, applied in chemical instruments and methods, sugar derivatives, sugar derivatives, etc., can solve the problems of easy emulsification, low extraction yield, easy environmental pollution, etc., and reduce equipment maintenance. cost, simplify the extraction process, and improve the effect of extraction efficiency

Active Publication Date: 2014-03-19
宁夏泰瑞制药股份有限公司
6 Cites 6 Cited by

AI-Extracted Technical Summary

Problems solved by technology

[0005]1) Organic solvents (including ethyl acetate and butyl acetate) are used in the production process, resulting in organic solvents in the generated wastewater, which is easy to pollute the environment
[0006]2) The process cycle of extraction and stripping is long
[0007]3) Low extraction yield
[0008]4) Emulsification is prone to occur during the extraction process
[0009]5) Higher production costs
[0011]1) A large amount of salt is used in the production process, and the used salt cannot be recycled and reused, and it is easy to pollute the environment
[0012]2) Salting out yield is low
[0014]1) Flat membran...
View more

Abstract

A method for producing an aseptic bulk drug tylosin salt by utilizing a tylosin fermentation broth is disclosed. The aseptic bulk drug tylosin salt is obtained by performing pretreatment, tubular porous ceramics membrane filtration, dilution, nanofiltration membrane nanofiltration, crystal water washing, acid-base neutralization, ultrafiltration and spray drying on the tylosin fermentation broth. The method helps to realize the stable efficient production of the bulk drug aseptic bulk drug tylosin salt. Also the method helps to simplify the extraction technology, improve the extraction yield of the tylosin salt, shorten the production period, reduce the cost and improve the yield of tylosin. The method helps to simplify the extraction technology of tylosin, shorten the production period by 4 hours or more and improve the extraction efficiency, and has the advantages of being energy-saving, capable of reducing environmental pollution, simple in operation, high in work efficiency and the like.

Application Domain

Sugar derivativesChemical industry +1

Technology Topic

UltrafiltrationNanofiltration +11

Examples

  • Experimental program(5)

Example Embodiment

[0047] Example 1
[0048] Turn on the fermentation tank and stir, and the speed is controlled at 10r/min. 10m 3 The tylosin fermentation broth (chemical titer is 13241μ/ml) is heated to 50°C, 10kg industrial oxalic acid is added, and the pH is adjusted to 3.2 with 20% hydrochloric acid, and stirring is continued for 20 minutes. The fermentation broth is transported by a high-pressure centrifugal pump to a stainless steel metal mesh with a filtration accuracy of 400 μm for filtration, and the tylosin residue is washed with drinking water with a pH of 5 to 6 (adjusted with 20% hydrochloric acid or sulfuric acid) to obtain tylosin Vegetarian filtrate 8.2m 3 , The chemical potency is 16955μ/ml. The yield of pretreatment was 105%.
[0049] Tylosin filtrate is filtered through a tubular porous ceramic membrane. Before filtering the filtrate, adjust the viscosity of the filtrate to 3892cps with purified water. In the process of membrane filtration, the pressure is controlled at 1-1.2 bar, and the temperature of the filtrate is controlled at 50-51°C. The material of the tubular porous ceramic membrane is mainly aluminum oxide, and the filtration precision of the membrane is 0.1μm. Membrane filtration is over, the filtrate volume is 9.4m 3 , The chemical potency is 14228μ/ml, and the yield of membrane filtration is 96.2%.
[0050] The temperature of the filtrate filtered by the membrane was reduced to 20°C, and the tylosin was diluted by adding purified water, and the chemical titer was reduced to 11382μ/ml, and then passed through the nanofiltration membrane. In the nanofiltration process, the material of the nanofiltration membrane is an aromatic polyamide composite nanofiltration membrane. The pressure is controlled at 2~2.2MPa, the temperature of the filtrate is controlled at 20~21℃, and the flow rate of nanofiltration is controlled at 400~420L/h. At the end of nanofiltration, top wash with purified water for 5 minutes, the volume of the filtrate is 3.2m 3 The chemical potency is 41335μ/ml, and the yield of nanofiltration is 98.9%.
[0051] Start stirring, control the rotation speed at 10r/min, reduce the temperature of the filtrate to 10°C, use 10% sodium carbonate filtrate to reach a pH of 10.2, and precipitate 122.4kg of tylosin crystals. After the crystals are precipitated, let it stand for 1h. After standing, the solid-liquid separation is performed, and the obtained solid tylosin is washed twice with purified water, and the amount of purified water is 184L each time.
[0052] Prepare a 10% tartaric acid solution with purified water, add it to the reactor containing tylosin crystals, start stirring, adjust the pH to 5.2, and then perform ultrafiltration. During the ultrafiltration process, the temperature of the tylosin salt solution is controlled at 20-21°C, the pressure is controlled at 0.3-0.5MPa, and the filtration rate is 2000-2200L/h. The material of the ultrafiltration membrane is polyvinylidene fluoride, and the filtration accuracy of the membrane is 0.1μm.
[0053] The tylosin salt solution after ultrafiltration enters the spray drying tower. During the spray drying process, the inlet air temperature is controlled to be 130~140℃, the outlet temperature is 40~50℃, the feed speed is 150r/min, the spray drying is completed, and the sterile raw material medicine tylosin salt is obtained, and the final product is extracted. The rate is 93.4%.

Example Embodiment

[0054] Example 2
[0055] Start the fermentation tank and stir, and the speed is controlled at 20r/min. 10m 3 Tylosin fermentation broth (chemical titer: 13152μ/ml) was heated to 55°C, 25kg sodium oxalate was added, and pH was adjusted to 4.1 with 20% sulfuric acid, and stirring was continued for 25 minutes. The fermentation broth is transported by a high-pressure centrifugal pump to a stainless steel metal mesh with a filtration accuracy of 450 μm for filtration, and the tylosin residue is topped with drinking water with a pH of 5 to 6 (adjusted with 20% hydrochloric acid or sulfuric acid) for 2 times. Lamectin filtrate 8.4m 3 , The chemical potency is 16503μ/ml. The yield of pretreatment was 105.4%.
[0056] Tylosin filtrate is filtered through a tubular porous ceramic membrane. Before filtering the filtrate, adjust the viscosity of the filtrate to 3725cps with purified water, and then pass through a nanofiltration membrane. In the membrane filtration process, the pressure is controlled at 1 to 1.2 bar, and the temperature of the filtrate is controlled at 54 to 55°C. The material of the tubular porous ceramic membrane is mainly silica, and the filtration accuracy of the membrane is 0.1μm. Membrane filtration is over, the filtrate volume is 9m 3 , The chemical potency is 14972μ/ml, and the yield of membrane filtration is 97.2%.
[0057] The temperature of the filtrate filtered by the membrane dropped to 25°C, and the tylosin was diluted by adding purified water, and the chemical titer dropped to 11229μ/ml. In the nanofiltration process, the material of the nanofiltration membrane is an aromatic polyamide composite nanofiltration membrane. The pressure is controlled at 2~2.2MPa, the temperature of the filtrate is controlled at 24~25℃, and the flow rate of nanofiltration is controlled at 450~460L/h. At the end of nanofiltration, top wash with purified water for 7 minutes, the volume of the filtrate is 2.6m 3 The chemical potency is 51411μ/ml, and the yield of nanofiltration is 99.2%.
[0058] Start stirring, control the speed at 15r/min, reduce the temperature of the filtrate to 8°C, use 10% potassium carbonate filtrate to reach a pH of 10.5, precipitate 128.7 kg of tylosin crystals, and stand for 1 hour after the crystals are precipitated. After standing, the solid-liquid separation is performed, and the obtained solid tylosin is washed twice with purified water, and the amount of purified water is 218L each time.
[0059] Prepare 10% lactic acid solution with purified water, add it to the reactor containing tylosin crystals, start stirring, adjust the pH to 5.6, and then perform ultrafiltration. During the ultrafiltration process, the temperature of the tylosin salt solution is controlled at 25~26℃, the pressure is controlled at 0.3~0.5MPa, and the filtration rate is 2400~2500L/h. The material of the ultrafiltration membrane is polyvinylidene fluoride, and the filtration accuracy of the membrane is 0.1μm.
[0060] The tylosin salt solution after ultrafiltration enters the spray drying tower. During the spray drying process, the inlet air temperature is controlled to be 130~140℃, the outlet temperature is 40~50℃, the feed speed is 150r/min, and the spray drying is finished, the sterile raw material medicine tylosin salt is obtained, and the final product is extracted. The rate was 94.2%.

Example Embodiment

[0061] Example 3
[0062] Turn on the fermentation tank and stir, and the speed is controlled at 30r/min. 10m 3 Tylosin fermentation broth (chemical titer: 130874μ/ml) was heated to 60°C, 50kg glutamic acid was added, and pH was adjusted to 4.9 with 20% hydrochloric acid, and stirring was continued for 30 minutes. The fermentation broth is transported by a high-pressure centrifugal pump to a stainless steel metal mesh with a filtration accuracy of 500 μm for filtration, and the tylosin residue is washed twice with drinking water (adjusted with 20% hydrochloric acid or sulfuric acid) with a pH of 5-6. Lamectin filtrate 8.1m 3 , The chemical potency is 14069μ/ml. The yield of pretreatment was 104.8%.
[0063] Tylosin filtrate is filtered through a tubular porous ceramic membrane. Before filtering the filtrate, adjust the viscosity of the filtrate to 3541cps with purified water, and then pass through a nanofiltration membrane. During the membrane filtration process, the pressure is controlled at 1 to 1.2 bar, and the temperature of the filtrate is controlled at 59 to 60°C. The material of the tubular porous ceramic membrane is silicon carbide, and the filtration accuracy of the membrane is 0.1μm. Membrane filtration is over, the filtrate volume is 9.5m 3 , The chemical potency is 11612μ/ml, and the yield of membrane filtration is 96.8%.
[0064] The temperature of the filtrate filtered by the membrane dropped to 29°C, and purified water was added to dilute tylosin, and the chemical titer dropped to 8130μ/ml. In the nanofiltration process, the material of the nanofiltration membrane is an aromatic polyamide composite nanofiltration membrane. The pressure is controlled at 2~2.2MPa, the temperature of the filtrate is controlled at 28~30℃, and the flow rate of nanofiltration is controlled at 490~500L/h. At the end of nanofiltration, top wash with purified water for 10 minutes, and the volume of the filtrate is 2.5m 3 The chemical potency is 43684μ/ml, and the yield of nanofiltration is 99.0%.
[0065] Start stirring, control the rotation speed at 20r/min, reduce the temperature of the filtrate to 5°C, and use 10% sodium bicarbonate with the pH value of the filtrate to 10.8. 105.1kg of tylosin crystals are precipitated, and the crystals are allowed to stand for 1h. After standing, the solid-liquid separation is performed, and the obtained solid tylosin is washed twice with purified water, and the amount of purified water is 210L each time.
[0066] Prepare a 10% phosphoric acid solution with purified water, add it to the reactor containing tylosin crystals, start stirring, adjust the pH to 5.9, and then perform ultrafiltration. During the ultrafiltration process, the temperature of the tylosin salt solution is controlled at 28-30°C, the pressure is controlled at 0.3-0.5MPa, and the filtration rate is 2800-3000L/h. The material of the ultrafiltration membrane is polyvinylidene fluoride, and the filtration accuracy of the membrane is 0.1μm.
[0067] The tylosin salt solution after ultrafiltration enters the spray drying tower. During the spray drying process, the inlet air temperature is controlled to be 130~140℃, the outlet temperature is 40~50℃, the feed speed is 150r/min, the spray drying is completed, and the sterile raw material medicine tylosin salt is obtained, and the final product is extracted. The rate was 93.8%.

PUM

PropertyMeasurementUnit
Viscosity3892.0cps
Viscosity3842.0cps

Description & Claims & Application Information

We can also present the details of the Description, Claims and Application information to help users get a comprehensive understanding of the technical details of the patent, such as background art, summary of invention, brief description of drawings, description of embodiments, and other original content. On the other hand, users can also determine the specific scope of protection of the technology through the list of claims; as well as understand the changes in the life cycle of the technology with the presentation of the patent timeline. Login to view more.

Similar technology patents

Digital pre-distortion correction method and device with low sampling rate feedback

PendingCN113612453AReduce bandwidth requirements and sample rate requirementsSimple extraction process
Owner:UNIV OF ELECTRONIC SCI & TECH OF CHINA

Medicinal extract for preventing and treating diabetes and application thereof

PendingCN114732841APromotes glucose uptakeSimple extraction process
Owner:KUNMING INST OF BOTANY - CHINESE ACAD OF SCI +1

One-step extraction method of Momordica saponin and polysaccharide with hypoglycemic activity in two-phase aqueous phase

ActiveCN108586560BAvoid low biological activitySimple extraction process
Owner:SHANTOU UNIV

Method for extracting potassium sodium salts from m-aminophenol alkali fusion wastewater

PendingCN112028313ASimple extraction processHigh extraction recovery
Owner:HEBEI JIANXIN CHEM IND CO LTD

Tournefortiasibirica polysaccharide preparation method and plant salt-resistant regulator

ActiveCN108912235ASimple extraction processgood effect
Owner:TOBACCO RES INST CHIN AGRI SCI ACAD

Classification and recommendation of technical efficacy words

  • Shorten the production cycle
  • Simple extraction process

Alcaligenes faecalis mutant strain and method for preparing curdlan by using alcaligenes faecalis mutant strain

ActiveCN104087531ASimple extraction processGood mass transfer and oxygen transfer
Owner:JIANGSU YIMING BIOLOGICAL SCI & TECH +1

Extracting method for L-alanine

ActiveCN106748847ASimple extraction processReduce equipment investment
Owner:QINHUANGDAO HUAHENG BIOENG CO LTD

High-activity tea pigment, and extraction method and application thereof

ActiveCN103478336Areduce dosageSimple extraction process
Owner:杭州茗褐生物科技有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products