CN113603731B - Method for separating Zhongshengmycin - Google Patents

Method for separating Zhongshengmycin Download PDF

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Publication number
CN113603731B
CN113603731B CN202111073835.6A CN202111073835A CN113603731B CN 113603731 B CN113603731 B CN 113603731B CN 202111073835 A CN202111073835 A CN 202111073835A CN 113603731 B CN113603731 B CN 113603731B
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yield
ceramic membrane
spray drying
zhongshengmycin
clear liquid
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CN113603731A (en
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王卫富
马文艳
闫军军
潘忠成
郑鹏飞
李蒲民
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Shaanxi Microbe Biotechnology Co ltd
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00Processes for the preparation of sugar derivatives
    • C07H1/06Separation; Purification
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H17/00Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
    • C07H17/02Heterocyclic radicals containing only nitrogen as ring hetero atoms

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  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
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  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)

Abstract

The invention relates to a method for separating Zhongshengmycin, which comprises the core process steps of filtering fermentation liquor by a rotary ceramic membrane, washing bacterial residues without supplementing water, and forcibly reducing the volume of concentrated liquor after centrifuging concentrated materials, thereby improving the production efficiency. After nanofiltration and concentration, the clear solution of the ceramic membrane is subjected to water mill type spray drying to form 25-35% of soluble crude drug product, and after flash evaporation and spray drying of concentrated material, 2-5% or 12-18% of insoluble granular preparation or powder product is obtained, solid waste is not generated in the whole production process, and the total yield reaches 86-93%. The invention solves the technical problem of the production process of the Zhongshengmycin, realizes the integrated production of products with different dosage forms, improves the production efficiency, effectively reduces the production cost and realizes the industrial target of clean production of the Zhongshengmycin.

Description

Method for separating Zhongshengmycin
Technical Field
The invention belongs to the technical field of agricultural antibiotic extraction, and particularly relates to an environment-friendly method for separating Zhongshengmycin.
Background
The chemical structure of the mesogenic fungus is composed of three parts of streptostalactam, gulosamine and lysine side chains, namely streptostacin F, E, D, C, B, A and streptostacin X respectively from 1 to 7 according to the number of the side chain lysines. The Zhongshengmycin is a broad-spectrum antibiotic, can resist gram-positive bacteria, gram-negative bacteria, mycobacterium, saccharomycetes and filamentous fungi, and has moderate toxicity to human and livestock. The bactericidal composition is mainly used for preventing and treating diseases such as apple ring spot, cucumber bacterial angular leaf spot, tomato bacterial wilt and the like, is used as an agricultural antibiotic bactericide with green, low toxicity and low residue, and has good market prospect.
The Chinese patent application with application number 201210515430.8 discloses a production method of raw powder of Zhongshengmycin, which comprises the steps of carrying out primary water separation on a fermentation liquor of Zhongshengmycin, adding mycelium separated by a ceramic membrane into concentrated solution for spray drying, and carrying out high-content water insoluble substances with the content of 12-24%, without producing solid hazardous waste, but with low content, evaporating and concentrating to obtain low yield, heavy color and poor quality.
The Chinese patent application with application number 202011030686.0 discloses a preparation method of a high-purity Zhongshengmycin mother drug, which comprises the steps of plate-frame separation, resin adsorption separation, nanofiltration concentration, active carbon treatment, plate-frame filtration and spray drying in sequence, wherein the content of the obtained Zhongshengmycin mother powder is more than 40%, the actual production yield is less than 70%, and solid hazardous waste is generated at the same time, so that the method is unfavorable for environmental control.
At present, the production process of the Zhongshengmycin manufacturer Fujiankaili and the technical proposal in patent report have lower quality of the original medicine or complex production flow, thus leading to lower yield and higher cost. Therefore, a more optimized process is lacking in the field of products, so that the requirements of the market on high-quality raw medicine products are met, and the environment-friendly pesticide production process with higher environmental protection efficiency and lower production cost is the two major problems which are urgently needed to be solved in the current antibiotic industry. According to the invention, the ceramic membrane is filtered, clear liquid is subjected to nanofiltration concentration, then spray drying is carried out to form a soluble crude drug product, and concentrated materials are subjected to flash evaporation and spray drying to obtain insoluble granular preparation or powder products, so that the integrated production of products with different dosage forms is realized, the production yield is improved, the production problem of environmental protection is solved, the production cost is effectively reduced, and the sustainable development and market application potential of the product are improved.
Disclosure of Invention
In order to solve the technical problems, the invention aims to provide an environment-friendly method for separating Zhongshengmycin, which comprises the following steps of filtering fermentation liquor by a rotary ceramic membrane, washing bacterial residues without supplementing water, centrifuging concentrated materials, forcibly reducing the volume of the concentrated liquid, concentrating clear liquid of the ceramic membrane by nanofiltration, spray-drying to form a soluble raw medicine product, and flash-drying the concentrated materials to obtain insoluble granular preparations or powder products. The invention realizes the integrated production of products with different dosage forms, solid waste is not generated in the whole production process, the production yield is improved, the environmental protection problem is solved, the green process target of the clean production of the Zhongshengmycin is realized, and the production cost is effectively reduced.
More specifically, the technical scheme adopted by the invention is as follows:
an environment-friendly method for separating Zhongshengmycin, which comprises the following process steps:
1) Filtering the fermentation liquid of the Zhongshengmycin by a rotary ceramic membrane, washing fungus residues without supplementing water, controlling the circulation rate of equipment, pressing the volume of concentrated material to the minimum liquid level, and collecting clear liquid;
2) The ceramic membrane concentrate enters a centrifugal machine, the volume is compressed, clear liquid is collected, and concentrated slag is pumped into a pulping tank;
3) Flash evaporation, spray drying and granulating the ceramic membrane concentrate or the centrifugal concentrate slag to form an insoluble granular preparation;
4) Concentrating and dialyzing the ceramic membrane clear solution or the centrifugal clear solution by a nanofiltration membrane, and then, feeding into a water mill type spray drying to form the soluble crude drug.
In a preferred embodiment of the invention, in the step (1), the average titer of the clear liquid obtained by filtering the fermentation broth of the Zhongshengmycin by the rotary ceramic membrane is not less than 90% of the titer of the fermentation tank, and the concentration ratio is 3.5-4.5 times.
In a preferred embodiment of the invention, in step (2), the ceramic membrane concentrate is filtered cyclically using a continuous feed centrifuge or the concentrate is filtered in a tube centrifuge at a concentration ratio of 2.5 to 3.0 times.
In the preferred embodiment of the invention, in the step (3), the ceramic membrane concentrate or the centrifugal concentrate slag is subjected to flash evaporation and spray drying to obtain the insoluble raw mesogenic powder with the content of 2-5% or 12-18%.
In a preferred embodiment of the present invention, in step (4), the ceramic membrane supernatant or the centrifugal supernatant is concentrated and then spray dried to obtain the soluble mesogenic agent with a content of 25-35%.
The production method finally obtains 2 to 5 percent or 12 to 18 percent of insoluble preparation particles of the Zhongshengmycin and 25 to 35 percent of soluble raw medicine, and the total production yield is between 86 and 93 percent.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides an environment-friendly method for separating Zhongshengmycin, fermentation liquor is filtered by a rotary ceramic membrane, bacterial residues are not required to be washed by water, concentrated materials are centrifuged, the volume of the concentrated materials is forcedly reduced, the production efficiency is improved, the integrated production of 2-5% or 12-18% insoluble preparation particles or powder products and 25-35% soluble raw material products in different dosage forms is realized, the total production yield is 86-93%, and the accounting production cost is reduced by more than 20%.
The invention solves the green process problem in the production process of the Zhongshengmycin, realizes that solid waste and dangerous waste are not generated in the whole production process of the Zhongshengmycin, further reduces the treatment risk and cost of the solid waste and dangerous waste, improves the production efficiency, effectively reduces the production cost, and realizes the green process target of high-quality clean production of the Zhongshengmycin.
Drawings
The invention is further illustrated in the following drawings, which are only illustrative and explanatory of the invention, and do not limit the scope of the invention:
FIG. 1 is a process flow diagram of the method for isolation of mesogenic substances according to the invention.
Detailed Description
The essential features of the invention are described below with the aid of examples, which are to be understood as illustrative and not limiting to the embodiments of the invention, the scope and core content of which are to be determined in accordance with the claims.
Example 1
1) Oxalic acid is carried out on the fermentation liquor until the pH value is 2.5-3.0, the volume of the fermentation liquor is 21-23m after acidification, the rotary ceramic membrane is used for filtering, water is not needed to be added in the middle for washing fungus residues, high-unit clear liquor of about 14-16m is produced, high-unit concentrated materials of 5-6m are produced, the average titer of a clear liquor tank is not less than 90% of the titer of a fermentation tank, the concentration ratio is 3.5-4.5 times, and the clear liquor yield is 68-72%;
2) Continuously feeding and circularly centrifuging ceramic membrane concentrate, supplementing water for 3-4m in the middle, washing bacterial residues, controlling bacterial residues titer between 2000-3500u/ml, generating low unit clear liquid with 5-6m and centrifugal concentrate residue with 2-3m, and obtaining 14-15% of centrifugal clear liquid yield;
3) 2-3m of centrifugal concentrate is subjected to flash evaporation, spray drying and granulation to obtain an insoluble particle preparation with the content of 2-5%, and the primary yield of flash evaporation and granulation is 90-93%;
4) Mixing ceramic membrane clear solution and centrifugal clear solution (15-20 m) and concentrating to 4.5-6.0 ten thousand units by nanofiltration, and performing water mill type spray drying to obtain a soluble crude drug with the content of 25-35%, wherein the primary spray drying yield is 86-88%;
5) Total yield accounting: 86-87%.
Example 2
1) Oxalic acid is carried out on the fermentation liquor until the pH value is 2.5-3.0, the volume of the fermentation liquor is 21-23m after acidification, the rotary ceramic membrane is used for filtering, water is not needed to be added in the middle for washing fungus residues, high-unit clear liquor of about 14-16m is produced, high-unit concentrated materials of 5-6m are produced, the average titer of a clear liquor tank is not less than 90% of the titer of a fermentation tank, the concentration ratio is 3.5-4.5 times, and the clear liquor yield is 68-72%;
2) The ceramic membrane concentrate is continuously fed and circularly centrifuged or tubular, water is not supplemented, and the residual 2-3m of concentrated residues are centrifuged to generate about 3m of centrifugate, and the yield of the centrifugate is 12-13%;
3) The centrifugal concentrate is subjected to flash evaporation, spray drying and granulation to obtain an insoluble granular preparation with the content of 12-18%, and the primary yield of flash evaporation and granulation is 90-93%;
4) Mixing ceramic membrane clear solution and centrifugal clear solution, concentrating to 4.5-6.0 ten thousand units, adding into water mill type spray drying to obtain soluble crude drug with content of 25-35%, and spray drying for one time with yield of 86-88%;
5) Total yield accounting: 88.0-90.0%.
Example 3
1) Oxalic acid is carried out on the fermentation liquor until the pH value is 2.5-3.0, the volume of the fermentation liquor is 21-23m after acidification, the rotary ceramic membrane is used for filtering, water is not needed to be added in the middle for washing fungus residues, high-unit clear liquor of about 14-16m is produced, high-unit concentrated materials of 5-6m are produced, the average titer of a clear liquor tank is not less than 90% of the titer of a fermentation tank, the concentration ratio is 3.5-4.5 times, and the clear liquor yield is 68-72%;
2) Continuously feeding ceramic membrane concentrate, circularly centrifuging or tubular separating, flash evaporating, spray drying and granulating 5-6m thick ceramic membrane concentrate to obtain insoluble granular preparation with content of 12-18%, and flash evaporating and granulating to obtain primary yield of 90-93%;
3) Concentrating the clear ceramic membrane solution to 5.5-6.5 ten thousand units, adding into a water mill, spray drying to obtain a soluble crude drug with the content of 25-35%, and spray drying for one time to obtain the yield of 86-88%;
4) Total yield accounting: 90.0-93.0%.
Example 4 (control Process 1)
1) Oxalic acid is carried out on the fermentation liquor to pH2.5-3.0, the volume of the fermentation liquor is 21-23m after acidification, the fermentation liquor is filtered by a conventional ceramic membrane, high-unit clear liquid (the average titer is not less than 90% of the titer of a fermentation tank) with the volume of about 12-13m is produced, the concentration ratio of the ceramic membrane concentrate with the volume of 7-8m is 2.5-3.0 times, and the clear liquid yield is 56-62%;
2) Concentrating the ceramic membrane clear liquid to 5.5-6.5 ten thousand units by vacuum evaporation, and concentrating the ceramic membrane clear liquid by evaporation to obtain the yield of 70-75%;
3) Mixing the evaporated concentrated solution and the ceramic concentrated solution, and then feeding the mixture into a water mill type spray drying device to obtain insoluble particle mother powder with the content of 12-24%, and spraying and drying once to obtain the yield of 86-88%;
4) Total yield accounting: 60.0-65.0%.
Example 5 (control Process 2)
1) Oxalic acid is carried out on the fermentation liquor to pH2.5-3.0, the volume of the fermentation liquor is 21-23m after acidification, the fermentation liquor is filtered by a conventional ceramic membrane, high-unit clear liquid (the average titer is not less than 90% of the titer of a fermentation tank) with the volume of about 12-13m is produced, the concentration ratio of the ceramic membrane concentrate with the volume of 7-8m is 2.5-3.0 times, and the total yield of clear liquid is 56-62%;
2) Concentrating the clear ceramic membrane solution to 4.5-5.0 ten thousand units by using a nanofiltration membrane, wherein the nanofiltration concentration yield is 88-90%;
3) Mixing the evaporated concentrated solution and the ceramic concentrated solution, and then feeding the mixture into a water mill type spray drying device to obtain insoluble particle mother powder with the content of 12-24%, and spraying and drying once to obtain the yield of 86-88%;
4) Total yield accounting: 75.0% -77.0%.
The foregoing is a further detailed description of the invention in connection with specific/preferred embodiments, and it is not intended that the invention be limited to such description. Several alternatives or modifications to these described embodiments should be considered to fall within the scope of the invention without departing from the inventive concept.

Claims (3)

1. The method for separating the Zhongshengmycin is characterized by comprising the following process steps of:
1) Oxalic acid treatment is carried out on the Zhongshengmycin fermentation liquor until the pH value is 2.5-3.0, the volume of the acidified fermentation liquor is 21-23m, the acidized fermentation liquor is filtered by a rotary ceramic membrane, the bacterium residues are not required to be washed by water in the middle, high-unit clear liquid of 14-16m and high-unit concentrated material of 5-6m are produced, the average titer of a clear liquid tank is not less than 90% of the titer of a fermentation tank, the concentration ratio is 3.5-4.5 times, and the clear liquid yield is 68-72%;
2) Continuously feeding and circularly centrifuging ceramic membrane concentrate, supplementing water for 3-4m in the middle, washing bacterial residues, controlling bacterial residues titer between 2000-3500u/ml, generating low unit clear liquid with 5-6m and centrifugal concentrate residue with 2-3m, and obtaining 14-15% of centrifugal clear liquid yield;
3) 2-3m of centrifugal concentrate is subjected to flash evaporation, spray drying and granulation to obtain an insoluble particle preparation with the content of 2-5%, and the primary yield of flash evaporation and granulation is 90-93%;
4) Mixing 15-20m ceramic membrane clear solution and centrifugal clear solution, nano-filtering and concentrating to 4.5-6.0 ten thousand units, and performing water mill type spray drying to obtain a soluble crude drug with the content of 25-35%, wherein the primary spray drying yield is 86-88%;
5) Total yield accounting: 86-87%.
2. The method for separating the Zhongshengmycin is characterized by comprising the following process steps of:
1) Oxalic acid treatment is carried out on the Zhongshengmycin fermentation liquor until the pH value is 2.5-3.0, the volume of the acidified fermentation liquor is 21-23m, the acidized fermentation liquor is filtered by a rotary ceramic membrane, the bacterium residues are not required to be washed by water in the middle, high-unit clear liquid of 14-16m and high-unit concentrated material of 5-6m are produced, the average titer of a clear liquid tank is not less than 90% of the titer of a fermentation tank, the concentration ratio is 3.5-4.5 times, and the clear liquid yield is 68-72%;
2) The ceramic membrane concentrate is continuously fed and circularly centrifuged or tubular, water is not supplemented, and the residual 2-3m of concentrated residues are centrifuged to generate about 3m of centrifugate, and the yield of the centrifugate is 12-13%;
3) The centrifugal concentrate is subjected to flash evaporation, spray drying and granulation to obtain an insoluble granular preparation with the content of 12-18%, and the primary yield of flash evaporation and granulation is 90-93%;
4) Mixing ceramic membrane clear solution and centrifugal clear solution, concentrating to 4.5-6.0 ten thousand units, adding into water mill type spray drying to obtain soluble crude drug with content of 25-35%, and spray drying for one time with yield of 86-88%;
5) Total yield accounting: 88.0-90.0%.
3. The method for separating the Zhongshengmycin is characterized by comprising the following process steps of:
1) Oxalic acid treatment is carried out on the Zhongshengmycin fermentation liquor until the pH value is 2.5-3.0, the volume of the acidified fermentation liquor is 21-23m, the acidized fermentation liquor is filtered by a rotary ceramic membrane, the bacterium residues are not required to be washed by water in the middle, high-unit clear liquid of 14-16m and high-unit concentrated material of 5-6m are produced, the average titer of a clear liquid tank is not less than 90% of the titer of a fermentation tank, the concentration ratio is 3.5-4.5 times, and the clear liquid yield is 68-72%;
2) The ceramic membrane concentrate is continuously fed, circularly centrifuged or tubular, and the 5-6m thick ceramic membrane concentrate is subjected to flash evaporation, spray drying and granulation to obtain an insoluble granular preparation with the content of 12-18%, wherein the primary yield of flash evaporation and granulation is 90-93%;
3) Concentrating the clear ceramic membrane solution to 5.5-6.5 ten thousand units, adding into a water mill, spray drying to obtain a soluble crude drug with the content of 25-35%, and spray drying for one time to obtain the yield of 86-88%;
4) Total yield accounting: 90.0-93.0%.
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CN113896753A (en) * 2021-11-16 2022-01-07 陕西麦可罗生物科技有限公司 Method for efficiently separating zhongshengmycin from fermentation liquor

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