CN112390806A - Method for improving extraction yield of spectinomycin - Google Patents
Method for improving extraction yield of spectinomycin Download PDFInfo
- Publication number
- CN112390806A CN112390806A CN202011164967.5A CN202011164967A CN112390806A CN 112390806 A CN112390806 A CN 112390806A CN 202011164967 A CN202011164967 A CN 202011164967A CN 112390806 A CN112390806 A CN 112390806A
- Authority
- CN
- China
- Prior art keywords
- spectinomycin
- filtrate
- solution
- ultrafiltration membrane
- filtration
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Abstract
The invention provides a method for improving the extraction yield of spectinomycin, which comprises the following steps: A. coarse filtration: acidifying spectinomycin fermentation liquor to pH2.0-4.0, and performing primary rough filtration by using an ultrafiltration membrane to obtain a crude filtrate; B. fine filtering: adjusting pH of the coarse filtrate to 5.5-6.5 with alkaline reagent, and filtering with ultrafiltration membrane for the second time to obtain fine filtrate; C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution; D. refining: removing bacterial endotoxin and heat source substances in the destaining solution by using an ultrafiltration membrane to obtain refined solution; E. concentration: concentrating the refined solution by using a nanofiltration membrane to obtain a concentrated solution; F. and (3) crystallizing and drying: and crystallizing and drying the concentrated solution to obtain a finished product. The method has the advantages of short extraction process, simple process, high production efficiency, low investment cost, good clarity of filtrate, high yield and low ineffective components.
Description
Technical Field
The invention belongs to the field of biological medicine, and particularly relates to a method for improving the extraction yield of spectinomycin.
Background
Spectinomycin is an aminoglycoside broad-spectrum antibiotic, and has antibacterial effects on gram-negative and gram-positive bacteria. Clinically, the spectinomycin specially treats the infection caused by neisseria, and the broad antibacterial spectrum and low toxicity of the spectinomycin also enable the spectinomycin to be applied to the field of pesticides or veterinary pharmacology as a feed additive.
At present, the production of spectinomycin adopts a microbiological method. Firstly, slant preparation of growth bacteria, then fermentation is carried out by taking starch, glucose and the like as raw materials, spectinomycin in fermentation liquor is extracted by ion exchange resin, the resin is eluted by acid, and the eluent is concentrated and then crystallized by solvent twice to obtain the product. The extraction method has the following defects:
1. the extraction process has long line, low production efficiency, high cost and low yield;
2. a large amount of acid-base wastewater is generated in the extraction process, the wastewater contains a large amount of antibiotics, has an inhibiting effect on microorganisms, and has poor biodegradability and high treatment difficulty.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides the spectinomycin extraction method which has the advantages of short process flow, high production efficiency, low production cost, greatly reduced three wastes and COD, low solvent consumption, high yield and low ineffective components.
The technical scheme adopted by the invention is as follows: a method for improving the extraction yield of spectinomycin comprises the following steps:
A. coarse filtration: acidifying spectinomycin fermentation liquor to pH2.0-4.0, and performing primary coarse filtration by using an ultrafiltration membrane to obtain a coarse filtrate;
B. fine filtering: b, adjusting the pH of the coarse filtrate obtained in the step A to 5.5-6.5 by using an alkaline reagent, and performing secondary filtration by using an ultrafiltration membrane to obtain fine filtrate;
C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution;
D. refining: removing bacterial endotoxin and heat source substances in the destaining solution by using an ultrafiltration membrane to obtain refined solution;
E. concentration: concentrating the refined solution by using a nanofiltration membrane to obtain a concentrated solution;
F. and (3) crystallizing and drying: and crystallizing and drying the concentrated solution to obtain a finished product.
Further, an acidic reagent used for acidification in the step A is hydrochloric acid, and the concentration of the hydrochloric acid is 3-6 mol/L.
Further, in the step B, the alkaline reagent is sodium hydroxide.
Further, the ultrafiltration membrane used in the step A, B, D is an ultrafiltration membrane with a molecular weight of 3000-100000 Da.
Furthermore, the mass volume ratio of the activated carbon adopted in the step C to the fine filter liquid is 0.1-1%.
Further, the nanofiltration membrane adopted in the step E is a nanofiltration membrane with the molecular weight of 200-500 Da.
The beneficial effects obtained by the invention are as follows: the spectinomycin meeting USP and EP standards is obtained by improving the extraction method, most of protein and pigment impurities are removed by using ultrafiltration membranes with different molecular weights to treat fermentation liquor and filtrate, the clarity of the obtained filtrate is high, a good foundation is provided for the subsequent process, the ion exchange process is removed, the discharge of waste water is reduced, the extraction process is shortened, the production efficiency is improved, the investment cost is reduced, the yield is high, and the ineffective components of the product are greatly reduced. The total extraction yield of spectinomycin is about 70 percent, which is higher than the current yield of about 50 percent.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments.
A method for improving the extraction yield of spectinomycin comprises the following steps: A. coarse filtration: acidifying spectinomycin fermentation liquor to pH2.0-4.0 by adopting hydrochloric acid with the concentration of 3-6 mol/L, and performing primary rough filtration by using an ultrafiltration membrane with the molecular weight of 3000-100000Da to obtain a rough filtrate; B. fine filtering: b, adjusting the pH of the coarse filtrate obtained in the step A to 5.5-6.5 by using sodium hydroxide, and performing secondary filtration by using an ultrafiltration membrane with the molecular weight of 3000-100000Da to obtain fine filtrate; C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution; D. refining: removing bacterial endotoxin and heat source substance in the decolored solution by using an ultrafiltration membrane with the molecular weight of 3000-100000Da to obtain refined solution; E. concentration: concentrating the refined solution with a nanofiltration membrane with molecular weight of 200-; F. and (3) crystallizing and drying: and crystallizing and drying the concentrated solution to obtain a finished product. And the mass volume ratio of the activated carbon and the fine filter liquid adopted in the step C is 0.1-1%.
Example 1
A method for improving the extraction yield of spectinomycin comprises the following steps: A. coarse filtration: acidifying spectinomycin fermentation liquor 60L and titer 8250U/mL by using hydrochloric acid with concentration of 5mol/L to pH 3.5, and performing primary rough filtration by using an ultrafiltration membrane with molecular weight of 60000Da to obtain a crude filtrate; b. Fine filtering: b, adjusting the pH of the coarse filtrate obtained in the step A to 5.5 by using sodium hydroxide, and performing secondary filtration by using an ultrafiltration membrane with the molecular weight of 30000Da to obtain fine filtrate; C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution; D. refining: removing bacterial endotoxin and heat source substance in the decolorized solution by using an ultrafiltration membrane with molecular weight of 3000Da to obtain refined solution; E. concentration: concentrating the refined solution with nanofiltration membrane with molecular weight of 200Da to obtain concentrated solution; F. and (3) crystallizing and drying: the concentrated solution is crystallized and dried to obtain 336.0g of spectinomycin finished product meeting CP and USP standards, the yield is 68 percent, and the purity is 98.2 percent.
Example 2
A method for improving the extraction yield of spectinomycin comprises the following steps: A. coarse filtration: acidifying 50L spectinomycin fermentation liquor with the titer of 7200U/mL by adopting hydrochloric acid with the concentration of 5mol/L to the pH value of 4.0, and carrying out primary rough filtration by using an ultrafiltration membrane with the molecular weight of 30000Da to obtain a crude filtrate; b. Fine filtering: b, adjusting the pH of the coarse filtrate obtained in the step A to 5.8 by using sodium hydroxide, and performing secondary filtration by using an ultrafiltration membrane with the molecular weight of 20000Da to obtain a fine filtrate; C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution; D. refining: removing bacterial endotoxin and heat source substance in the decolorized solution by using an ultrafiltration membrane with molecular weight of 3000Da to obtain refined solution; E. concentration: concentrating the refined solution with nanofiltration membrane with molecular weight of 300Da to obtain concentrated solution; F. and (3) crystallizing and drying: and crystallizing and drying the concentrated solution to obtain 252.3g of spectinomycin finished product meeting CP and USP standards, wherein the yield is 70.1 percent, and the purity is 97.2 percent.
Example 3
A method for improving the extraction yield of spectinomycin comprises the following steps: A. coarse filtration: acidifying 58L spectinomycin fermentation liquor and 7458U/mL titer by using hydrochloric acid with the concentration of 4mol/L to the pH value of 2.0, and performing primary coarse filtration by using an ultrafiltration membrane with the molecular weight of 100000Da to obtain a coarse filtrate; b. Fine filtering: b, adjusting the pH of the coarse filtrate obtained in the step A to 6.2 by using sodium hydroxide, and performing secondary filtration by using an ultrafiltration membrane with the molecular weight of 60000Da to obtain a fine filtrate; C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution; D. refining: removing bacterial endotoxin and heat source substance in the decolorized solution by using an ultrafiltration membrane with a molecular weight of 3000Da to obtain a refined solution; E. concentration: concentrating the refined solution with nanofiltration membrane with molecular weight of 200Da to obtain concentrated solution; F. and (3) crystallizing and drying: and crystallizing and drying the concentrated solution to obtain 311.4g of spectinomycin finished product meeting CP and USP standards, wherein the yield is 72.1 percent, and the purity is 96.2 percent.
Example 4
A method for improving the extraction yield of spectinomycin comprises the following steps: A. coarse filtration: acidifying spectinomycin fermentation liquor 55L and the titer of 7812U/mL by hydrochloric acid with the concentration of 4mol/L to the pH value of 4.0, and performing primary rough filtration by using an ultrafiltration membrane with the molecular weight of 80000Da to obtain a rough filtrate; b. Fine filtering: b, adjusting the pH of the coarse filtrate obtained in the step A to 5.8 by using sodium hydroxide, and performing secondary filtration by using an ultrafiltration membrane with the molecular weight of 40000Da to obtain a fine filtrate; C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution; D. refining: removing bacterial endotoxin and heat source substance in the decolorized solution with ultrafiltration membrane with molecular weight of 5000Da to obtain refined solution; E. concentration: concentrating the refined solution with nanofiltration membrane with molecular weight of 300Da to obtain concentrated solution; F. and (3) crystallizing and drying: crystallizing and drying the concentrated solution to obtain 297.3g of spectinomycin finished product meeting CP and USP standards, with yield of 69.2% and purity of 96.1%
Example 5
A method for improving the extraction yield of spectinomycin comprises the following steps: A. coarse filtration: acidifying 56L of spectinomycin fermentation liquor with a titer of 7743U/mL by using hydrochloric acid with a concentration of 5mol/L to pH 4.0, and carrying out primary rough filtration by using an ultrafiltration membrane with a molecular weight of 80000Da to obtain a rough filtrate; b. Fine filtering: b, adjusting the pH of the coarse filtrate obtained in the step A to 5.5 by using sodium hydroxide, and performing secondary filtration by using an ultrafiltration membrane with the molecular weight of 60000Da to obtain a fine filtrate; C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution; D. refining: removing bacterial endotoxin and heat source substance in the decolorized solution by using an ultrafiltration membrane with the molecular weight of 4000Da to obtain refined solution; E. concentration: concentrating the refined solution with nanofiltration membrane with molecular weight of 300Da to obtain concentrated solution; F. and (3) crystallizing and drying: the concentrated solution is crystallized and dried to obtain 305.4g of spectinomycin finished product meeting CP and USP standards, the yield is 68.0 percent, and the purity is 97.1 percent.
Comparative examples
50L of spectinomycin fermentation liquor with the titer of 7743U/ml is adjusted to the pH value of 2.0 by hydrochloric acid with the concentration of 5mol/L, solid-liquid separation is carried out, and filtrate is collected; adjusting pH of the filtrate to 7.0 with 20% ammonia water solution, passing through ion exchange resin, eluting with hydrochloric acid, and concentrating the eluate with nanofiltration membrane; adding active carbon for decolorizing, filtering, vacuum concentrating the decolorized solution, crystallizing, filtering, and drying the obtained crystal to obtain spectinomycin 226.3g, with yield of 58.4% and purity of 95.1%
The invention solves the problems of overlong extraction line, low production efficiency, high input cost, low yield, high ineffective component, short extraction process, simple process, high production efficiency, low input cost, good filtrate clarity, high yield and low ineffective component in the extraction process of spectinomycin in the prior art.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (6)
1. A method for improving the extraction yield of spectinomycin is characterized by comprising the following steps: the method comprises the following steps:
A. coarse filtration: acidifying spectinomycin fermentation liquor to pH2.0-4.0, and performing primary coarse filtration by using an ultrafiltration membrane to obtain a coarse filtrate;
B. fine filtering: b, adjusting the pH of the coarse filtrate obtained in the step A to 5.5-6.5 by using an alkaline reagent, and performing secondary filtration by using an ultrafiltration membrane to obtain fine filtrate;
C. and (3) decoloring: adding activated carbon into the fine filtrate for decolorization and filtration to obtain a decolorized solution;
D. refining: removing bacterial endotoxin and heat source substances in the destaining solution by using an ultrafiltration membrane to obtain refined solution;
E. concentration: concentrating the refined solution by using a nanofiltration membrane to obtain a concentrated solution;
F. and (3) crystallizing and drying: and crystallizing and drying the concentrated solution to obtain a finished product.
2. The method for improving the extraction yield of spectinomycin according to claim 1, characterized in that: and B, using hydrochloric acid as an acidic reagent for acidification in the step A, wherein the concentration of the hydrochloric acid is 3-6 mol/L.
3. The method for improving the extraction yield of spectinomycin according to claim 1, characterized in that: and in the step B, the alkaline reagent is sodium hydroxide.
4. The method for improving the extraction yield of spectinomycin according to claim 1, characterized in that: the ultrafiltration membrane used in step A, B, D is an ultrafiltration membrane with a molecular weight of 3000-100000 Da.
5. The method for improving the extraction yield of spectinomycin according to claim 1, characterized in that: and the mass volume ratio of the activated carbon and the fine filter liquid adopted in the step C is 0.1-1%.
6. The method for improving the extraction yield of spectinomycin according to claim 1, characterized in that: the nanofiltration membrane adopted in the step E is a nanofiltration membrane with the molecular weight of 200-500 Da.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011164967.5A CN112390806A (en) | 2020-10-27 | 2020-10-27 | Method for improving extraction yield of spectinomycin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011164967.5A CN112390806A (en) | 2020-10-27 | 2020-10-27 | Method for improving extraction yield of spectinomycin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN112390806A true CN112390806A (en) | 2021-02-23 |
Family
ID=74597216
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011164967.5A Pending CN112390806A (en) | 2020-10-27 | 2020-10-27 | Method for improving extraction yield of spectinomycin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112390806A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113861212A (en) * | 2021-10-11 | 2021-12-31 | 河北圣雪大成唐山制药有限责任公司 | Method for improving turbidity of spectinomycin hydrochloride product |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1554773A (en) * | 2003-12-26 | 2004-12-15 | 三达膜科技（厦门）有限公司 | Method for extracting fermentikve macrolide antibiotics using membrane |
| CN109081844A (en) * | 2018-10-10 | 2018-12-25 | 山东鲁抗医药股份有限公司 | A method of extracting spectinomycin from fermentation culture medium |
| CN111217837A (en) * | 2018-11-24 | 2020-06-02 | 江苏久吾高科技股份有限公司 | Method and device for purifying antibiotic fermentation liquor |
| CN112557331A (en) * | 2020-12-28 | 2021-03-26 | 唐山市食品药品综合检验检测中心(唐山市畜牧水产品质量监测中心) | Method for rapidly determining titer of spectinomycin in spectinomycin extracting solution |
-
2020
- 2020-10-27 CN CN202011164967.5A patent/CN112390806A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1554773A (en) * | 2003-12-26 | 2004-12-15 | 三达膜科技（厦门）有限公司 | Method for extracting fermentikve macrolide antibiotics using membrane |
| CN109081844A (en) * | 2018-10-10 | 2018-12-25 | 山东鲁抗医药股份有限公司 | A method of extracting spectinomycin from fermentation culture medium |
| CN111217837A (en) * | 2018-11-24 | 2020-06-02 | 江苏久吾高科技股份有限公司 | Method and device for purifying antibiotic fermentation liquor |
| CN112557331A (en) * | 2020-12-28 | 2021-03-26 | 唐山市食品药品综合检验检测中心(唐山市畜牧水产品质量监测中心) | Method for rapidly determining titer of spectinomycin in spectinomycin extracting solution |
Non-Patent Citations (3)
| Title |
|---|
| 宋伟杰等: "微滤技术在发酵工业中的应用", 《生物产业技术》 * |
| 杨元娟主编: "《生物药物检测技术》", 31 January 2017 * |
| 王怀伟: "优化大观霉素提取工艺", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113861212A (en) * | 2021-10-11 | 2021-12-31 | 河北圣雪大成唐山制药有限责任公司 | Method for improving turbidity of spectinomycin hydrochloride product |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11555049B2 (en) | Method for separation and purification of n-acetylglucosamine | |
| CN108822163B (en) | Comprehensive cyclic production method of D-glucosamine hydrochloride | |
| CN107513030B (en) | Method for separating and purifying L-hydroxyproline from L-hydroxyproline fermentation liquor | |
| CN109369730B (en) | Sialic acid and extraction method thereof | |
| CN211111802U (en) | Purification device of antibiotic zymotic fluid | |
| EP2208732B1 (en) | Deshydroxy vancomycin, the preparation, pharmaceutical composition and the use | |
| CN109081844B (en) | Method for extracting spectinomycin from fermentation culture | |
| CN102040638A (en) | Method for preparing nonsolvent of high-purity natamycin | |
| CN1415758A (en) | Technique for producing raw material of vancomycin hydrochloride | |
| CN110759959B (en) | Vitamin B is separated and extracted from fermentation liquor 12 Method (2) | |
| CN112390806A (en) | Method for improving extraction yield of spectinomycin | |
| CN103772086B (en) | Pretreatment process for preparing fractions of marine microorganism small molecule metabolites | |
| CN113005161A (en) | Preparation method of polysialic acid and polysialic acid product | |
| CN100463912C (en) | Membrane separating and purifying process for aminoglycoside antibiotics | |
| CN109942646B (en) | Method for extracting lincomycin hydrochloride | |
| CN115215949B (en) | Sodium hyaluronate and purification method thereof | |
| CN112409426B (en) | Preparation method of sisomicin sulfate | |
| CN108299220B (en) | Method for extracting L-4-hydroxyisoleucine from fermentation catalytic liquid | |
| CN103408638B (en) | A kind of preparation technology of vancomycin crystallization | |
| CN109705174B (en) | Method for extracting tobramycin | |
| CN110452275B (en) | Preparation method of high-purity kasugamycin | |
| CN110117310B (en) | Purification method of daptomycin | |
| CN113045610A (en) | Method for extracting glucosamine from N-acetylglucosamine fermentation liquor | |
| CN1554662A (en) | Process for preparing high purity acarbose | |
| CN111100823A (en) | Polymyxin B sulfate production strain, preparation method and application of polymyxin B sulfate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20210223 |
|
| RJ01 | Rejection of invention patent application after publication |