Process method for separating and purifying bitespiramycin

Abstract

The invention relates to a process method for separating and purifying bitespiramycin. The method comprises the following steps: (1) an ester extract liquid containing bitespiramycin is subjected to three-stage countercurrent washing, such that a washed ester solution is obtained; (2) the washed ester solution is subjected to first stripping with a phosphate solution, such that primary water extract containing bitespiramycin is obtained; (2) the primary water extract is extracted with ester, such that an ester extract liquid with concentrated bitespiramycin is obtained; (4) the ester extract liquid is subjected to secondary stripping with a phosphate solution, such that secondary water extract containing bitespiramycin is obtained; and (5) ethanol is added; and lye is dropped in for crystallizing, such that a bitespiramycin finished product is obtained. Compared with prior arts, the method provided by the invention adopts three-stage countercurrent extraction washing and a multiple-time solvent extraction method with variable phase ratios, such that impurities with relatively high polarity can be removed, and the effective component can be enriched. Ethanol is added for regulating crystalline system polarity. Low-concentration lye is used for regulating crystalline liquid pH level. With the method, impurities among the components can be effectively removed, and effective component can be enriched.

Description

technical field

[0001] The invention relates to a process method for separating and purifying bitspiramycin, which belongs to the technical field of antibiotic separation and purification. Background technique

[0002] Macrolides antibiotics are one of the most widely used antibacterial drugs. The parent molecular structure is a 14-16-membered ring macrolide, and the hydroxyl group on the lactone ring is bonded to 1-3 molecules of sugar or amino sugar linked. More than 100 such antibiotics have been discovered so far, and the commonly used ones are: 14-membered ring erythromycin (Erythromycin) and its derivatives Roxithromycin (Roxithromycin), clarithromycin (Clarithromycin), 15-membered ring red Mycin derivatives Azithromycin, the 16-membered ring mainly includes Josamycin, Kitasamycin, Midecamycin, Platenomycin, Tylos Tylosin, Spiramycin and its derivatives.

[0003] Bitespiramycin, also known as Kelimycin and Shengjimycin, is a multi-component mixture composed of acyla...

Examples

Embodiment 1

[0049] (1) Three-stage countercurrent washing: the butyl acetate extract containing the titrepiromycin titer of 7234u / ml was washed with 0.8% NaH 2 PO 4 The solution was washed countercurrently by a three-stage centrifuge. The washing temperature was 20° C., and the washing phase was water phase: ester phase = 1:1.5, so that the after-washing solution of bitspiramycin with an ester phase titer of 5593u / ml was obtained.

[0050] (2) Buffer back extraction: the separated butyl acetate washing liquid is 0.7% NaH with pH=2.2, mass fraction 2 PO 4 Solution stripping, the stripping phase is the water phase: ester phase = 1:4.5, the water and ester are mixed and stirred, and the water phase is mixed with H 3 PO 4 Adjust the pH of the water phase to 3.60, let stand to separate the liquids, and obtain the back-extraction solution of Bitespiramycin with a titer of 21708u / ml in the water phase.

[0051] (3) Butyl acetate extraction: adjust the pH of the aqueous phase phase extract o...

Embodiment 2

[0056] (1) Three-stage countercurrent washing: the butyl acetate extract containing the titrepiromycin titer of 9078u / ml was washed with 1% NaH 2 PO 4 The solution was washed countercurrently by a three-stage centrifuge. The washing temperature was 20° C., and the washing phase was water phase: ester phase = 1:1.5, so that the after-washing solution of bitspiramycin with the titer of the ester phase was 5249u / ml was obtained.

[0057] (2) Buffer stripping: the separated butyl acetate washing liquid is washed with 0.7% NaH of pH=2.2 2 PO 4 Solution stripping, the stripping phase is the water phase: ester phase = 1:4, the water and ester are mixed and stirred, and the water phase is mixed with H 3 PO 4 Adjust the pH of the water phase to 3.85, let stand to separate the liquids, and obtain the back-extraction solution of Bitespiramycin with a titer of 20468u / ml in the water phase.

[0058] (3) Butyl acetate extraction: adjust the pH of the aqueous phase extract of bispirulin...

Embodiment 3

[0063] (1) Three-stage countercurrent washing: the butyl acetate extract containing the titrepiromycin titer of 8578u / ml was washed with 0.9% NaH 2 PO 4 The solution was washed countercurrently by a three-stage centrifuge. The washing temperature was 20° C., and the washing phase was water phase: ester phase = 1:1.5, so that the after-washing solution of bitspiramycin with an ester phase titer of 6091u / ml was obtained.

[0064] (2) Buffer stripping: the separated butyl acetate washing liquid is washed with 0.7% NaH of pH=2.2 2 PO 4 Solution stripping, the stripping phase is the water phase: ester phase = 1:3.5, the water and ester are mixed and stirred, and the water phase is mixed with H 3 PO 4 Adjust the pH of the water phase to 3.75, let stand to separate the liquids, and obtain the back-extraction solution of Bitespiramycin with a titer of 20972u / ml in the water phase.

[0065] (3) Butyl acetate extraction: adjust the pH of the aqueous phase phase extract of Bitespira...

technical field

[0001] The invention relates to a process method for separating and purifying bitspiramycin, which belongs to the technical field of antibiotic separation and purification. Background technique

[0002] Macrolides antibiotics are one of the most widely used antibacterial drugs. The parent molecular structure is a 14-16-membered ring macrolide, and the hydroxyl group on the lactone ring is bonded to 1-3 molecules of sugar or amino sugar linked. More than 100 such antibiotics have been discovered so far, and the commonly used ones are: 14-membered ring erythromycin (Erythromycin) and its derivatives Roxithromycin (Roxithromycin), clarithromycin (Clarithromycin), 15-membered ring red Mycin derivatives Azithromycin, the 16-membered ring mainly includes Josamycin, Kitasamycin, Midecamycin, Platenomycin, Tylos Tylosin, Spiramycin and its derivatives.

[0003] Bitespiramycin, also known as Kelimycin and Shengjimycin, is a multi-component mixture composed of acyla...

Examples

Embodiment 1

[0049] (1) Three-stage countercurrent washing: the butyl acetate extract containing the titrepiromycin titer of 7234u / ml was washed with 0.8% NaH 2 PO 4 The solution was washed countercurrently by a three-stage centrifuge. The washing temperature was 20° C., and the washing phase was water phase: ester phase = 1:1.5, so that the after-washing solution of bitspiramycin with an ester phase titer of 5593u / ml was obtained.

[0050] (2) Buffer back extraction: the separated butyl acetate washing liquid is 0.7% NaH with pH=2.2, mass fraction 2 PO 4 Solution stripping, the stripping phase is the water phase: ester phase = 1:4.5, the water and ester are mixed and stirred, and the water phase is mixed with H 3 PO 4 Adjust the pH of the water phase to 3.60, let stand to separate the liquids, and obtain the back-extraction solution of Bitespiramycin with a titer of 21708u / ml in the water phase.

[0051] (3) Butyl acetate extraction: adjust the pH of the aqueous phase phase extract o...

Embodiment 2

[0056] (1) Three-stage countercurrent washing: the butyl acetate extract containing the titrepiromycin titer of 9078u / ml was washed with 1% NaH 2 PO 4 The solution was washed countercurrently by a three-stage centrifuge. The washing temperature was 20° C., and the washing phase was water phase: ester phase = 1:1.5, so that the after-washing solution of bitspiramycin with the titer of the ester phase was 5249u / ml was obtained.

[0057] (2) Buffer stripping: the separated butyl acetate washing liquid is washed with 0.7% NaH of pH=2.2 2 PO 4 Solution stripping, the stripping phase is the water phase: ester phase = 1:4, the water and ester are mixed and stirred, and the water phase is mixed with H 3 PO 4 Adjust the pH of the water phase to 3.85, let stand to separate the liquids, and obtain the back-extraction solution of Bitespiramycin with a titer of 20468u / ml in the water phase.

[0058] (3) Butyl acetate extraction: adjust the pH of the aqueous phase extract of bispirulin...

Embodiment 3

[0063] (1) Three-stage countercurrent washing: the butyl acetate extract containing the titrepiromycin titer of 8578u / ml was washed with 0.9% NaH 2 PO 4 The solution was washed countercurrently by a three-stage centrifuge. The washing temperature was 20° C., and the washing phase was water phase: ester phase = 1:1.5, so that the after-washing solution of bitspiramycin with an ester phase titer of 6091u / ml was obtained.

[0064] (2) Buffer stripping: the separated butyl acetate washing liquid is washed with 0.7% NaH of pH=2.2 2 PO 4 Solution stripping, the stripping phase is the water phase: ester phase = 1:3.5, the water and ester are mixed and stirred, and the water phase is mixed with H 3 PO 4 Adjust the pH of the water phase to 3.75, let stand to separate the liquids, and obtain the back-extraction solution of Bitespiramycin with a titer of 20972u / ml in the water phase.

[0065] (3) Butyl acetate extraction: adjust the pH of the aqueous phase phase extract of Bitespira...

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