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CN110317841A - A kind of griseofulvin fermentation production medium - Google Patents

A kind of griseofulvin fermentation production medium Download PDF

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Publication number
CN110317841A
CN110317841A CN201910648868.5A CN201910648868A CN110317841A CN 110317841 A CN110317841 A CN 110317841A CN 201910648868 A CN201910648868 A CN 201910648868A CN 110317841 A CN110317841 A CN 110317841A
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Prior art keywords
griseofulvin
fermentation
flour
gpe
sulfate
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CN201910648868.5A
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CN110317841B (en
Inventor
胡志远
杨春艳
于彩岩
安丽艳
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INNER MONGOLIA GELINTE PHARMACEUTICAL Co Ltd
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INNER MONGOLIA GELINTE PHARMACEUTICAL Co Ltd
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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14Fungi; Culture media therefor
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/02Oxygen as only ring hetero atoms
    • C12P17/04Oxygen as only ring hetero atoms containing a five-membered hetero ring, e.g. griseofulvin, vitamin C

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
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  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Medicinal Chemistry (AREA)
  • Mycology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Botany (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

The invention discloses a kind of griseofulvin fermentation production mediums, are formulated by the raw material of following weight percent: long rice flour 6%, corn flour 5%, tapioca flour 3%, potassium dihydrogen phosphate 0.6%, calcium carbonate 0.4%, sodium nitrate 0.1%, ammonium sulfate 0.1%, ferrous sulfate 0.1%, sodium chloride 0.8%, potassium chloride 0.7%, magnesium sulfate 0.1%, GPE GPE type 0.05%, surplus is water.Fermentation broth viscosity of the present invention reduces, and fermentation unit is stablized in 28000-30000 μ g/ml, fermentation period contraction 45 hours, reduces fermentation energy consumption, reduces cost, high income.

Description

A kind of griseofulvin fermentation production medium
The present invention relates to raw material medicament preparation, in particular to a kind of griseofulvin fermentation production mediums for technical field.
Background technique griseofulvin be antibiotics bulk pharmaceutical chemicals, English name Griseofulvin, Chinese nickname grisein, Crystallite griseofulvin, English alias Fulcin, Fulcine, Fulvicin, Fungivin, Grifulvin, Grisactin, Grisefulin, Griseofulvinum, [CAS] 126-07-8, this product are the attritive powder of white or off-white color;This product master There is good antibacterial action to superficial mycosis such as trichophyta, sporidiole bacteria, Epidermophytons.
Griseofulvin is treated suitable for various tinea diseases, including favus of the scalp, barber's itch, ringworm of the body, jock itch, tinea pedis and onychomycosis.
Currently, the method for preparing griseofulvin, a, griseofulvin fermented and cultured some cycles heat inactivation, sheet frame solid-liquid point It pelletizes drying from, filter cake mycelium.B, acetone extract obtains griseofulvin acetone extract liquid;C, griseofulvin acetone extract liquid is living Property carbon decoloring, destainer condensing crystallizing obtain griseofulvin crude product;D, griseofulvin crude product acetone solution, griseofulvin acetone Lysate activity carbon decoloring, condensing crystallizing obtains griseofulvin recrystallizer to destainer again;E, griseofulvin recrystallizer butanol Washing, then with ethanol washing, drying, pulverize to obtain griseofulvin bulk pharmaceutical chemicals.
Summary of the invention makes to consume in production process the object of the present invention is to provide a kind of griseofulvin fermentation production medium Energy is low, it is short to reduce cost, fermentation period, improves fermentation unit, improves production efficiency.
The technical solution adopted by the invention is as follows:
A kind of griseofulvin fermentation production medium, is formulated by the raw material of following weight percent: long rice flour 6%, Corn flour 5%, tapioca flour 3%, potassium dihydrogen phosphate 0.6%, calcium carbonate 0.4%, sodium nitrate 0.1%, ammonium sulfate 0.1%, sulfuric acid Ferrous iron 0.1%, sodium chloride 0.8%, potassium chloride 0.7%, magnesium sulfate 0.1%, GPE GPE type 0.05%, surplus is water.
The present invention has the advantages that carbon source ingredient and proportion in 1, adjustment fermentation medium, through production process monitoring data Show that carbon source proportion is long rice flour 6%, corn flour 5%, tapioca flour 3% can be such that fermentation broth viscosity reduces, and fermentation unit, which is stablized, to exist 28000-30000 μ g/ml fermentation period contraction 45 hours, reduces fermentation energy consumption, reduces cost;
2, compared with comparative formula, adjustment potassium dihydrogen phosphate is 0.6%, and calcium carbonate 0.4%, fermentation liquid pH is reduced by 6.8 To 5.8, sampled to observe under the microscope, strain growth is more significant than the strain growth speed in control test recipe in fermentation liquid It speeds;
3, gas-liquid mixed effect in fermentor can be improved by suitable GPE type GPE being added, and improve the speed of oxygen in fermentor Rate is conducive to strain growth and improves yield;
4, this test recipe is in industrialized production application, and filters than control test recipe, high income about 16%.
The invention will be further described below specific embodiment.
A kind of griseofulvin fermentation production medium, is formulated by the raw material of following weight percent: long rice flour 6%, Corn flour 5%, tapioca flour 3%, potassium dihydrogen phosphate 0.6%, calcium carbonate 0.4%, sodium nitrate 0.1%, ammonium sulfate 0.1%, sulfuric acid Ferrous iron 0.1%, sodium chloride 0.8%, potassium chloride 0.7%, magnesium sulfate 0.1%, GPE GPE type 0.05%, surplus is water.
It is as follows using above-mentioned culture medium production griseofulvin method:
A, it by above-mentioned culture medium with 121~126 DEG C of fermentor of loading is postponed, maintains sterilize within 30 minutes, is down to 30 to tank temperature Degree, inoculation, fermentation, condition of culture: initial medium pH=5.8, cultivation temperature: 29 DEG C ± 1 DEG C, air mass flow: 2500~ 3600m3/ h, tank pressure: 0.01~0.05MPa is cultivated to 340 hours, heat inactivation uses plate compression in ferment middle feed supplement For machine by mycelium and separation of fermentative broth, mycelium adds calcium oxide granulation, drying, is packed into extraction column and adds acetone extract;
B, acetone extract obtains griseofulvin acetone extract liquid;
C, griseofulvin acetone extract liquid activity carbon decoloring, destainer condensing crystallizing obtain griseofulvin crude product;
D, knot is concentrated in griseofulvin crude product acetone solution, griseofulvin acetone solution liquid activity carbon decoloring, destainer again Crystalline substance obtains griseofulvin recrystallizer;
E, griseofulvin recrystallizer butanol wash, then with ethanol washing, drying, pulverize to obtain griseofulvin raw material Medicine.
Comparative experiments:
Test recipe (used medium of the present invention)
Long rice flour 6%, corn flour 5%, tapioca flour 3%, potassium dihydrogen phosphate 0.6%, calcium carbonate 0.4%, sodium nitrate 0.1%, ammonium sulfate 0.1%, ferrous sulfate 0.1%, sodium chloride 0.8%, potassium chloride 0.7%, magnesium sulfate 0.1%, GPE GPE type 0.05%, surplus is water.
Comparative formula (culture medium used before our company)
Long rice flour 15%, potassium dihydrogen phosphate 0.4%, calcium carbonate 0.6%, sodium nitrate 0.1%, ammonium sulfate 0.1%, sulfuric acid are sub- Iron 0.1%, sodium chloride 0.8%, potassium chloride 0.7%, magnesium sulfate 0.1%, surplus are water.
By above-mentioned two formulas ingredient, after disinfection, by seed culture fluid be depressed into fermentor culture after culture, mid-term feed supplement, Inactivation, mycelium and separation of fermentative broth, extraction, decoloration, crystallization, washing, drying, pulverize to obtain griseofulvin raw material at granulation Medicine.By testing comparison result such as table three times:
1 comparative test table of table
Conclusion (of pressure testing): through test recipe compared with comparative formula, the fermentation liquid filtering velocity in test recipe is significantly improved, mistake It is higher than comparative formula by about 16% to filter yield, pH is reduced to 5.8 by 6.8 after disappearing, and fermentation titer is stablized in 28000-30000 μ g/ml, Fermentation period shortens about 45 hours, annual to save 1,500,000 yuan, improves efficiency for enterprise, improves yield, it is close to create economic benefit 10000000 profits.

Claims (1)

1. a kind of griseofulvin fermentation production medium, which is characterized in that be formulated by the raw material of following weight percent: Xian Rice flour 6%, corn flour 5%, tapioca flour 3%, potassium dihydrogen phosphate 0.6%, calcium carbonate 0.4%, sodium nitrate 0.1%, ammonium sulfate 0.1%, ferrous sulfate 0.1%, sodium chloride 0.8%, potassium chloride 0.7%, magnesium sulfate 0.1%, GPE GPE type 0.05%, residue Amount is water.
CN201910648868.5A 2019-07-10 2019-07-10 Fermentation production culture medium for griseofulvin Active CN110317841B (en)

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CN110317841B CN110317841B (en) 2022-11-22

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112094874A (en) * 2020-09-16 2020-12-18 内蒙古格林特制药有限责任公司 Culture medium for producing griseofulvin through fermentation

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101812489A (en) * 2010-04-29 2010-08-25 赤峰制药股份有限公司 Culture medium for producing griseofulvin by fermentation
CN103275047A (en) * 2013-05-23 2013-09-04 内蒙古格林特制药有限责任公司 Preparation method of griseofulvin
CN106480121A (en) * 2016-09-27 2017-03-08 宁夏泰瑞制药股份有限公司 A kind of culture medium of utilization penicillium patulum producing griseofulvin by fermentation and cultural method
CN108641969A (en) * 2018-06-21 2018-10-12 赤峰制药股份有限公司 A kind of griseofulvin production bacterium culture medium

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101812489A (en) * 2010-04-29 2010-08-25 赤峰制药股份有限公司 Culture medium for producing griseofulvin by fermentation
CN103275047A (en) * 2013-05-23 2013-09-04 内蒙古格林特制药有限责任公司 Preparation method of griseofulvin
CN106480121A (en) * 2016-09-27 2017-03-08 宁夏泰瑞制药股份有限公司 A kind of culture medium of utilization penicillium patulum producing griseofulvin by fermentation and cultural method
CN108641969A (en) * 2018-06-21 2018-10-12 赤峰制药股份有限公司 A kind of griseofulvin production bacterium culture medium

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112094874A (en) * 2020-09-16 2020-12-18 内蒙古格林特制药有限责任公司 Culture medium for producing griseofulvin through fermentation

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Denomination of invention: A culture medium for the fermentation production of griseofulvin

Granted publication date: 20221122

Pledgee: Huaxia Bank Co.,Ltd. Chifeng Branch

Pledgor: INNER MONGOLIA GLINT PHARMACEUTICAL CO.,LTD.

Registration number: Y2024150000049