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Slow-release composition containing capric acid

A slow-release composition and technology of capric acid, applied in the field of biomedicine, can solve the problems of low fermentation unit and fermentation contamination, achieve good growth status, increase fermentation unit, and reduce the probability of contamination

Active Publication Date: 2013-10-16
鲁南新时代生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In summary, it can be known that there is currently no relevant literature on the preparation of daptomycin by shake flask fermentation, and since the addition of capric acid during the shake flask fermentation process cannot realize automatic micro-volume continuous feeding, multiple feeds are generally used. Not only is it easy to cause fermentation infection, but also because the concentration of capric acid is too high to inhibit the growth of bacteria, so that the fermentation unit is lower

Method used

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  • Slow-release composition containing capric acid

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1: the preparation method of the sustained-release composition containing capric acid

[0034] Sustained release composition proportioning (percentage by weight):

[0035]

Capric acid (%)

Ethanol (%)

Stearic acid (%)

Polyethylene glycol (%)

Agar powder (%)

water(%)

Composition 1

3

3

0.5

1.0

1.0

91.5

Composition 2

10

8

1.0

2.0

2.0

77.0

Composition 3

6

6

0.7

1.1

1.2

85.0

[0036] Mix the weighed capric acid and ethanol evenly according to the ratio, and filter the membrane to sterilize;

[0037] Mix the weighed stearic acid, polyethylene glycol, agar powder and water according to the proportion, and sterilize the mixture at 115°C for 20 minutes;

[0038] on the aseptic operating table The obtained sterile mixture was added to the temperature dropped to 70 ℃ In the mixture, mix even...

Embodiment 2

[0041] Embodiment 2: the preparation of fermentation medium

[0042] Slant medium (g / L): 4 yeast extracts, 10 malt extracts, 4 glucose, 15 agar, prepared as a feed solution according to the formula, adjusted to pH 7.2, and sterilized at 121°C for 30 minutes;

[0043] Seed medium (g / L): dextrin 20, peptone 10, yeast extract 3, K 2 HPO 4 0.1, NaCl 0.2, prepare the feed solution according to the formula, adjust the pH to 7.0, and sterilize at 121°C for 30 minutes;

[0044] Fermentation medium formula (g / L): dextrin 30, glucose 6, soybean powder 15, yeast powder 4, FeSO 4 7H 2 O 0.5,K 2 HPO 4 0.2, MgSO 4 7H 2 O 0.1, prepare the feed solution according to the formula, adjust the pH to 7.2, and sterilize at 121°C for 30 minutes.

Embodiment 3

[0045] Example 3: Preparation of daptomycin by adding capric acid and fermenting

[0046] a. inoculate Streptomyces roseospora NRRL11379 on the slant medium, and culture aerobically at 30° C. for 10 days;

[0047] b. inoculate the bacteria cultured in step a on 30 ml seed medium, and vibrate at 30°C and 220rpm for 48h;

[0048] c. Inoculate the bacterium cultivated in b into the fermentation medium according to the inoculum size of 8%, and vibrate at 30°C and 220rpm for 8 days;

[0049] d. Start to add capric acid since the 36h of fermentation and cultivation, add a mixed solution containing 3.6ml capric acid once per liter of fermented liquid (the mixed solution contains capric acid and ethanol, and its weight ratio is 1: 1), every interval Add once every 24 hours, until the end of 204 hours of fermentation, add 6 times in total;

[0050] e. The Shimadzu LC-20A liquid chromatograph was used to detect daptomycin, and after adding decanoic acid, samples were taken every 24 hour...

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Abstract

The invention belongs to the field of biomedicine, and relates to a slow-release composition containing capric acid, particularly application of a slow-release composition containing capric acid in preparation of Daptomycin by fermentation. A certain amount of the slow-release composition containing capric acid can be supplemented at a specific time in the Daptomycin fermentation and production process, thereby synthesizing the Daptomycin. The invention reduces the number of times of shake flask fermentation and material supplementation, and lowers the probability of microbiological contamination; the slow-release capric acid reduces the toxicity for bacteria, and ensures good growth conditions for bacteria; and compared with the traditional batch-by-batch material supplementation method,the unit of the shake flask fermentation is increased by 4.1-5.8 times.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to a slow-release composition containing capric acid, in particular to an application of the slow-release composition containing capric acid in a method for fermenting and preparing daptomycin. Background technique [0002] Daptomycin (chemical formula 1 is the chemical formula of daptomycin) is a cyclic lipopeptide extracted from the fermentation broth of Streptomyces (S. reseosporus). It not only has a novel chemical structure, but also has The mode of action is also different from that of any approved antibiotic: it disrupts bacterial cell membrane function in several ways, thereby rapidly killing Gram-positive bacteria. In addition to its ability to act on most clinically relevant Gram-positive bacteria, daptomycin is still potent in vitro against isolated strains that have been resistant to methicillin, vancomycin, and linezolid. active. [0003] [0004] Chemical formula one [0...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P21/02C12R1/465
Inventor 赵志全郭朝江王成王召娜
Owner 鲁南新时代生物技术有限公司