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A kind of purification method of tobramycin

A kind of technology of tobramycin and purification method, applied in the field of medicine, can solve the problem of high impurity content of tobramycin

Active Publication Date: 2018-11-09
LIVZON NEW NORTH RIVER PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the contriver finds that the tobramycin impurity content prepared according to this report is high, needs to carry out further improvement to it

Method used

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  • A kind of purification method of tobramycin
  • A kind of purification method of tobramycin
  • A kind of purification method of tobramycin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] The tobramycin activity unit in the tobramycin hydrolyzate is not less than 10000u / ml, adjust the pH to 8.0 with hydrochloric acid, calculate the amount of the column solution according to the adsorption capacity of the D151 resin chromatography column, and use 3.0- Wash with 5.0% ammonium sulfate to remove impurities, and wash according to 25% of the amount on the column. After washing, use 0.1-2.0mol / L ammonia water gradient elution, the initial flow rate of ammonia water elution is 1200-1400ml / min, every 4 Measure the flow once an hour. When the mixture of kanamycin B and tobramycin begins to appear, start to collect in sections. Change the flow of ammonia elution to 450-550ml / min. Measure the flow every 2 hours. TLC method is used for the whole process Take control.

[0028] Start the vacuum system, condensation system. When the vacuum degree is ≤-0.07MPa, concentrate while feeding, control T≤70°C, and control the volume of the concentrated solution to be between 0...

Embodiment 2

[0030] Get the concentrated solution that embodiment 1 obtains, be divided into 2 batches, carry out the test of experiment A and experiment B respectively, experimental procedure and experimental result are as follows:

[0031] Experiment A:

[0032] Ammonia water adjusts the pH value of the concentrated solution of Example 1 to 8.00, passes through the D151 resin chromatography column, washes and removes impurities with 3% ammonium sulfate solution, washes by 25% of the amount on the column, and controls the flow rate at 0.40 ± 0.1BV to Thin-layer chromatography detects that when the color spot of the washing impurity component should be ≤ 2% of the TB color spot, stop washing, elute with ammonia water, and collect the ammonia water eluate.

[0033] Experiment B:

[0034] Ammonia water adjusts the pH value of the concentrated solution of Example 1 to 8.00, passes it through the D151 resin chromatography column, washes and removes impurities with 3%-5% ammonium sulfate solut...

Embodiment 3

[0044] Get 6 parts of the ammonia eluent obtained in Experiment B of Example 2 and concentrate, and concentrate 500ml of the ammonia eluent obtained in Experiment B of Example 2, and adjust the pH value to 4.0, 4.3, 4.5, 5.0, 5.5, respectively, with hydrochloric acid. 6.0, into the D122 resin chromatography column, the experimental conditions of the D122 resin chromatography column are glass column diameter-to-height ratio 1:8, resin load 500ml, pure water elution flow rate 100ml / h, collect the eluate. Concentrate and spray dry to obtain tobramycin. The results are shown in Table 2.

[0045] Table 2

[0046]

[0047]

[0048] Conclusion: 5.578g of tobramycin single component in the ammonia eluent obtained in Experiment B of Example 2, and when the pH value reaches 4.0, 4.3, 4.5, 5.0, 5.5, 6.0 respectively, the obtained tobramycin single component The components are 5.382g, 5.531g, 5.425g, 5.313g, 4.921g, 4.529g, and the yields are 96.5%, 99.2%, 97.3%, 95.2%, 88.2%, 81.2%...

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Abstract

The invention provides a tobramycin purification method.The tobramycin purification method includes steps of (1) adding hydrochloric acid into tobramycin hydrolysate to obtain pH at 8.00, washing with ammonium sulfate solution and eluting with ammonium hydroxide sequentially through macroporous weak-acid cation exchange resin to collect ammonium hydroxide eluent; (2) concentrating the collected ammonia hydroxide eluent in the step (1); (3) adding ammonium hydroxide into the concentrate in the step (2) to obtain pH at 8.00, introducing the macroporous weak-acid cation exchange resin, washing with the ammonium sulfate solution to remove impurity, eluting the ammonium sulfate and collecting the ammonium hydroxide eluent; adding hydrochloric acid into the ammonium hydroxide eluent to obtain pH in the range of 4.00-5.50, and introducing the macroporous weak-acid cation exchange resin and eluting with pure water; (4) concentrating the ammonium hydroxide eluent collected in the step (3), crystalizing, and atomizing to dry and obtain finished product tobramycin.

Description

technical field [0001] The invention belongs to the technical field of medicine, in particular, the invention relates to a method for purifying tobramycin. Background technique [0002] Tobramycin, also known as tobramycin, is an aminoglycoside antibiotic that can be used to treat a variety of bacterial infections, especially those caused by Gram-negative bacteria. Tobramycin is obtained by submerged fermentation of Streptomyces obscurus, and the main products of the fermentation process are abramycin, 6”-O-carbamyl kanamycin B and 6”-O-carbamyl tobramycin Bramycin, the latter two are hydrolyzed to generate kanamycin B and tobramycin respectively. Because the physical and chemical properties of these three main components produced by fermentation are similar, especially kanamycin B (Kb) and tobramycin, the structure is only different by one hydroxyl group, so its chemical extraction and purification is more complicated than other aminoglycoside antibiotics, reducing kanamyc...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H15/234C07H1/06
CPCC07H1/06C07H15/234
Inventor 李敬辉谢国财陈果
Owner LIVZON NEW NORTH RIVER PHARMA
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