CN105177102A - Preparation method of penicillin - Google Patents

Preparation method of penicillin Download PDF

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Publication number
CN105177102A
CN105177102A CN201510668236.7A CN201510668236A CN105177102A CN 105177102 A CN105177102 A CN 105177102A CN 201510668236 A CN201510668236 A CN 201510668236A CN 105177102 A CN105177102 A CN 105177102A
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China
Prior art keywords
penicillin
selenium
fermentation
making method
butyl acetate
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CN201510668236.7A
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Chinese (zh)
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霍进铭
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Individual
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Individual
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Abstract

The invention discloses a preparation method of penicillin. The preparation method of penicillin comprises the steps of adding a certain amount of selenium in butyl acetate, mixing to obtain a butyl acetate solution with a selenium concentration of 0.5 to 1.5mg/L. By adding selenium in a fermentation culture medium, fermentation liquid with penicillin content of 4.43g/L and the content of impurity A of 0.78 percent is prepared by adopting the fermentation method disclosed by the invention, the fermentation period is 138h, the content of penicillin is improved, the content of the impurity A of the penicillin is obviously reduced, the fermentation period is shortened, the price of selenium-containing substances is low and thereby the production cost is lower.

Description

A kind of making method of penicillin
Technical field
The present invention relates to the making method technical field of penicillin, particularly relate to a kind of making method of penicillin.
Background technology
Penicillin is a kind of efficient, low toxicity, clinical application important microbiotic widely.Succeeding in developing of it greatly strengthen the ability that the mankind resist bacterial infection, has driven the birth of microbiotic family.The new era by antibiotic therapy disease has been started in its appearance.Perfect by many decades, penicillin injection and oral penicillin can treat the diseases such as pneumonia, pulmonary tuberculosis, meningitis, endocarditis, diphtheria, anthrax respectively.After penicillin, the microbiotic such as Streptomycin sulphate, paraxin, terramycin, tsiklomitsin constantly produce, and enhance the ability of human treatment's communicable disease.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, a kind of making method of penicillin is provided.
Technical scheme of the present invention is as follows: the making method that the invention provides a kind of penicillin, comprises the following steps:
A, a certain amount of selenium will be added in N-BUTYL ACETATE, be mixed to get the N-BUTYL ACETATE solution that selenium concentration of element is 0.5-1.5mg/L;
B, in precipitation vessel the N-BUTYL ACETATE solution of gained in settling step a, obtain crystal, and stir this crystal slurry, pH value is adjusted to required degree continuously, until precipitate completely, obtain crystal precipitation;
C, to be placed in actinomycete fermentation substratum by the throw out of gained in step b and ferment, obtain penicillin fermentation liquid, add selenium in described fermention medium, the concentration of selenium element is 2 ~ 21mg/L.
The present invention is preferred, and described fermention medium is seed culture medium, fermentation culture or slant medium.
The present invention is preferred, and described seed culture medium moiety is: W-Gum is 6-10g/L; Glucose is 12-20g/L; Corn steep liquor is 10-20g/L; Soybean cake powder is 6-10g/L; KH 2pO 4for 0.5-1.0g/L; MgSO 4for 0.5-1.0g/L; CaCO 3for 15-20g/L; PH7.0-7.2.
The present invention is preferred, and described slant medium moiety is: glucose is 12-20g/L; Peptone is 1-5g/L; KCl is 0.1-0.5g/L; K 2hPO 4for 0.2-1.0g/L; MgSO 4for 0.2-0.5g/L; Agar is 10-20g/L; PH7.0-7.2.
The present invention is preferred, and described fermention medium moiety is: W-Gum is 20-30g/L; Glucose is 20-50g/L; Corn steep liquor is 5-10g/L; Soybean cake powder is 13-20g/L; Sodium Glutamate is 0.2-1.0g/L; FeCl 3for 0.2-0.5g/L; K 2hPO 4for 0.2-1.0g/L; CaCO 3for 0.2-2.0g/L; PH7.0-7.2.
Beneficial effect of the present invention is as follows:
Adopt such scheme, fermentation process of the present invention is by adding the mode of selenium in the fermentation medium, preparing Penicillin Content is 4.43g/L, and Impurity A content is the fermented liquid of 0.78%, and fermentation period is 138h, Penicillin Content improves, penicillin Impurity A content significantly reduces, and fermentation period shortens, and, cheap containing selenium material, thus production cost is lower.
Accompanying drawing explanation
Fig. 1 is the schema of the making method of a kind of penicillin of the present invention.
Embodiment
Below in conjunction with the drawings and specific embodiments, the present invention is described in detail.
Refer to Fig. 1, the invention provides a kind of making method of penicillin, comprise the following steps:
A, a certain amount of selenium will be added in N-BUTYL ACETATE, be mixed to get the N-BUTYL ACETATE solution that selenium concentration of element is 0.75mg/L;
B, in precipitation vessel the N-BUTYL ACETATE solution of gained in settling step a, obtain crystal, and stir this crystal slurry, pH value is adjusted to required degree continuously, until precipitate completely, obtain crystal precipitation;
C, to be placed in actinomycete fermentation substratum by the throw out of gained in step b and ferment, obtain penicillin fermentation liquid, add selenium in described fermention medium, the concentration of selenium element is 11mg/L.
According in step c when fermentation 22h, stream adds the selenium solution that selenium concentration of element is 869mg/L, and stream dosage is 2% of original fermented solution volume, and it is 1h that stream adds the time.
Described substratum is seed culture medium, fermentation culture or slant medium.
Described seed culture medium moiety is: W-Gum is 6-10g/L; Glucose is 12-20g/L; Corn steep liquor is 10-20g/L; Soybean cake powder is 6-10g/L; KH 2pO 4for 0.5-1.0g/L; MgSO 4for 0.5-1.0g/L; CaCO 3for 15-20g/L; PH7.0-7.2.
Described slant medium moiety is: glucose is 12-20g/L; Peptone is 1-5g/L; KCl is 0.1-0.5g/L; K 2hPO 4for 0.2-1.0g/L; MgSO 4for 0.2-0.5g/L; Agar is 10-20g/L; PH7.0-7.2.
Described fermention medium moiety is: W-Gum is 20-30g/L; Glucose is 20-50g/L; Corn steep liquor is 5-10g/L; Soybean cake powder is 13-20g/L; Sodium Glutamate is 0.2-1.0g/L; FeCl 3for 0.2-0.5g/L; K 2hPO 4for 0.2-1.0g/L; CaCO 3for 0.2-2.0g/L; PH7.0-7.2.
In sum, fermentation process of the present invention is by adding the mode of selenium in the fermentation medium, preparing Penicillin Content is 4.43g/L, and Impurity A content is the fermented liquid of 0.78%, and fermentation period is 138h, Penicillin Content improves, penicillin Impurity A content significantly reduces, and fermentation period shortens, and, cheap containing selenium material, thus production cost is lower.
These are only preferred embodiment of the present invention, be not limited to the present invention, all any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.

Claims (6)

1. a making method for penicillin, is characterized in that, comprises the following steps:
A, a certain amount of selenium will be added in N-BUTYL ACETATE, be mixed to get the N-BUTYL ACETATE solution that selenium concentration of element is 0.5-1.5mg/L;
B, in precipitation vessel the N-BUTYL ACETATE solution of gained in settling step a, obtain crystal, and stir this crystal slurry, pH value is adjusted to required degree continuously, until precipitate completely, obtain crystal precipitation;
C, to be placed in actinomycete fermentation substratum by the throw out of gained in step b and ferment, obtain penicillin fermentation liquid, add selenium in described fermention medium, the concentration of selenium element is 2 ~ 21mg/L.
2. the making method of a kind of penicillin according to claim 1, it is characterized in that, according in step c when fermentation 20-24h, stream adds the selenium solution that selenium concentration of element is 100-1000mg/L, stream dosage is the 1-2% of original fermented solution volume, and it is 0.5-1h that stream adds the time.
3. the making method of a kind of penicillin according to claim 1, is characterized in that, described fermention medium is seed culture medium, fermentation culture or slant medium.
4. the making method of a kind of penicillin according to claim 3, is characterized in that, described seed culture medium moiety is: W-Gum is 6-10g/L; Glucose is 12-20g/L; Corn steep liquor is 10-20g/L; Soybean cake powder is 6-10g/L; KH 2pO 4for 0.5-1.0g/L; MgSO 4for 0.5-1.0g/L; CaCO 3for 15-20g/L; PH7.0-7.2.
5. the making method of a kind of penicillin according to claim 3, is characterized in that, described slant medium moiety is: glucose is 12-20g/L; Peptone is 1-5g/L; KCl is 0.1-0.5g/L; K 2hPO 4for 0.2-1.0g/L; MgSO 4for 0.2-0.5g/L; Agar is 10-20g/L; PH7.0-7.2.
6. the making method of a kind of penicillin according to claim 3, is characterized in that, described fermention medium moiety is: W-Gum is 20-30g/L; Glucose is 20-50g/L; Corn steep liquor is 5-10g/L; Soybean cake powder is 13-20g/L; Sodium Glutamate is 0.2-1.0g/L; FeCl 3for 0.2-0.5g/L; K 2hPO 4for 0.2-1.0g/L; CaCO 3for 0.2-2.0g/L; PH7.0-7.2.
CN201510668236.7A 2015-10-17 2015-10-17 Preparation method of penicillin Pending CN105177102A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109777851A (en) * 2017-11-15 2019-05-21 华东理工大学 A method of improving penicillin biofermentation yield

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1191221A (en) * 1997-12-31 1998-08-26 华北制药股份有限公司 Process for one-shot crystallization of sodium penicillin
CN103834571A (en) * 2012-11-21 2014-06-04 青岛百草汇中草药研究所 Selection breeding method of gradient high concentration penicillin medium for penicillium chrysogenum

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1191221A (en) * 1997-12-31 1998-08-26 华北制药股份有限公司 Process for one-shot crystallization of sodium penicillin
CN103834571A (en) * 2012-11-21 2014-06-04 青岛百草汇中草药研究所 Selection breeding method of gradient high concentration penicillin medium for penicillium chrysogenum

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
储炬等: "特殊前体在抗生素生物合成中的作用", 《国外医药抗生素分册》 *
吴旭国: "浅谈青霉素的生产工艺过程", 《民营科技》 *
山东农学院生物系: "《工业微生物学》", 31 December 1972 *
秦丽艳等: "直接结晶法制备青霉素钠工艺研究", 《河北化工》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109777851A (en) * 2017-11-15 2019-05-21 华东理工大学 A method of improving penicillin biofermentation yield
CN109777851B (en) * 2017-11-15 2022-08-23 华东理工大学 Method for improving penicillin biological fermentation yield

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Application publication date: 20151223