Fed-batch feeding method in fermentation production of neomycin sulfate

A neomycin sulfate and feeding technology, applied in fermentation and other directions, can solve the problems of bacterial contamination risk, high nutrient concentration and delayed feeding time in the entire feeding system, so as to reduce the risk of bacterial contamination and achieve high conversion rate. , the effect of strong mycelial metabolism

Active Publication Date: 2021-03-19
YICHANG SANXIA PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Although the above-mentioned automatic metering cup feeding method reduces the labor intensity and the risk of human operation, it also avoids the problem of excessive one-time feeding to a certain extent. However, this set of feeding system involves a large number of pipeline valves, which is easy to form a dead angle for sterilization, and is more likely to cause the risk of bacterial contamination to the entire feeding system, and it is inconvenient to maintain. Substances with high concentration and viscosity, such as sugar, will often stick to the liquid level electrode, affecting the signal transmission of the liquid level electrode, causing problems such as inaccurate measurement or signal delay delays in feeding time

Method used

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  • Fed-batch feeding method in fermentation production of neomycin sulfate
  • Fed-batch feeding method in fermentation production of neomycin sulfate
  • Fed-batch feeding method in fermentation production of neomycin sulfate

Examples

Experimental program
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Embodiment 1

[0037] A fed-batch feeding method in the fermentative production of neomycin sulfate, the method may further comprise the steps:

[0038] Step 1: Connect the feeding pipeline 1 directly to the neomycin sulfate fermenter 2, and set a flow meter 3 and a pneumatic diaphragm valve 4 in sequence on the feeding pipeline 1 according to the feeding direction.

[0039] Step 2: Determine the time interval H of each sampling.

[0040] Step 3: every other sampling time interval H, the sampling staff samples the fermented liquid in the neomycin sulfate fermenter 2 to detect indicators such as reducing sugar and ammoniacal nitrogen, and determines the total amount of a sampling time interval H in combination with the metabolism of the fermented liquid. Feeding amount S, calculate the feeding rate V of this sampling time interval, the calculation formula is:

[0041] Feed rate V = total feed volume S / sampling interval H

[0042] S, the unit is L; H, the unit is hour.

[0043] Step 4: If...

Embodiment 2

[0063] After the second branch factory of Three Gorges Pharmaceutical Co., Ltd. adopts the method described in the present invention in the neomycin sulfate fermentation process, the dissolved oxygen in the tank is more stable, the mycelium metabolism is more vigorous, and the biological potency is obviously increased. Metering cup feeding and the second branch factory adopt the method of the present invention to select 3 batches of tanks with the same or close cycle to do comparative experiments. The first branch factory selects fermenter batches F353 / 0696, F356 / 0698, F358 / 0700, and the second branch factory selects The batch numbers of fermenters are F309 / 247, F312 / 248, and F303 / 249. The comparison results are as follows:

[0064] (1) Comparison of dissolved oxygen in the tank: The period of 60h to 84h was selected for the comparison of dissolved oxygen in the experimental tank. At this stage, the metabolism is relatively vigorous, the amount of feed is large, and the fluctua...

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Abstract

The invention discloses a fed-batch feeding method in a fermentation production of neomycin sulfate. The method comprises the following steps: step 1, sequentially arranging a flow meter and a pneumatic diaphragm valve on a feeding pipeline according to a feeding direction; step 2, determining a time interval H of each sampling; step 3, determining the total material supplementing amount S and calculating a material supplementing rate V; step 4, setting a material supplementing period t; step 5, determining a material supplementing instantaneous rate V; step 6, calculating starting t; step 7,calculating closing t; and step 8, completing fed-batch feeding in a fermentation production of neomycin sulfate. The provided fed-batch feeding method in a fermentation production of neomycin sulfateomits a metering tank and a large number of pipeline valves, accurate fed-batch feeding of a fermentation tank is achieved through the pneumatic diaphragm valve, a manual diaphragm valve, a blow-downvalve and an electromagnetic flowmeter, operation is easy, no sterilization dead angle exists, a risk of microorganism contamination of a feeding system is reduced, and sterilization times of a material supplementing system are reduced.

Description

technical field [0001] The invention relates to the technical field of biopharmaceuticals, in particular to a fed-batch feeding method in the fermentative production of neomycin sulfate. Background technique [0002] At present, fed-batch feeding method (referring to a method of continuously adding some nutrients to the fermentation system during the batch fermentation process) is widely used in the antibiotic fermentation industry, but in the domestic fermentation production of neomycin sulfate The main reason is that in the neomycin sulfate fermentation process, a large amount of carbon source and nitrogen source with relatively high substrate concentration need to be supplemented as nutrients (such as sugar material), and the substrate concentration is as high as 40%, and there is a certain Viscous, if feed feeding is used, the feeding rate is low, and the sugar material is easy to block the pipeline valve, which brings inconvenience to maintenance and easily causes steri...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12P19/52
CPCC12P19/52
Inventor 刘铭郑新曾勇李文豪肖金华王翀舒玉婷廖鹏
Owner YICHANG SANXIA PHARMA
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