Method for separating and preparing high-purity Moxidectin membrane

Abstract

The invention discloses a method for separating and preparing a high-purity Moxidectin membrane, and belongs to the technical field of pharmaceutical chemistry. The method comprises the following steps: performing membrane filtration on a pre-purified Nemadectin solution; after extraction with dichloromethane, removing solvents by using conventional concentration; successively performing a protection feeding reaction, an oxidation reaction, an oximation reaction and a protection removing reaction on concentrate to obtain a Moxidectin crude solution; filtering to remove impurities through a membrane separation technique; obtaining a high-purity Moxidectin concentrated solution through a membrane concentration technique. The method disclosed by the invention uses the membrane separation technique to replace column chromatography and a macroporous resin adsorption and separation method, the technique is stable, controllable, simple and practical, the industrialization is easy, the dosage of the solvents is reduced, and a high-temperature solvent removing process of a material solution is omitted, so that the degradation risk of products is reduced, the product purity, the product quality and the product yield are improved, at the same time, the energy resources are saved, and the production cost is reduced.

Description

technical field

[0001] The invention relates to the technical field of medicinal chemistry, in particular to a membrane separation preparation method for high-purity moxidectine. Background technique

[0002] Moxidectin (INN: Moxidectin) is a macrolide agricultural antibiotic, mainly used to treat parasitic diseases in animals such as cattle and sheep, and can be fermented by Streptomyces to produce Nemadectin (INN: Nemadectin) , and then obtained by chemical reaction, the structural formulas of nimoctine and moxictine are as formula (1).

[0003]

[0004] U.S. Patent No. 4916154A discloses a method for preparing moxictin, which involves solid-liquid separation of the fermented liquid produced by Streptomyces fermentation, extraction of the nimoctine solution obtained after leaching, silica gel column chromatography, gel layer Nemoctine obtained by analysis with a purity of more than 90% (HPLC), the purified nemoctine is obtained through up-protection, oxidation, deprote...

Examples

Embodiment 1

[0028] The steps of the method for preparing high-purity moxictine in this embodiment are as follows:

[0029] (1) The fermented liquid produced by Streptomyces fermentation undergoes solid-liquid separation, and the pre-purified liquid of nemoctine obtained after leaching has a purity of 15.6%, which contains 80 g of solids with a concentration of 1.5%, and is pumped into polyethersulfone hollow fiber microfiltration Membrane filtration, control pump pressure 0.1-0.7MP. The membrane filtrate was received to obtain a filtrate with a purity of 20%.

[0030] The above-mentioned filtrate is pumped into a roll-type ultrafiltration membrane with a molecular weight cut-off of 3000 for filtration, and the pump pressure is controlled at 0.5-0.9MP to receive the filtrate to obtain a filtrate with a purity of 52.5%.

[0031] (2) The nimoctine solution after ultrafiltration in step (1) is pumped into a roll-type nanofiltration membrane with a molecular weight cut off of 200 for concentr...

Embodiment 2

[0038] The steps of the method for preparing high-purity moxictine in this embodiment are as follows:

[0039] (1) The fermented liquid produced by Streptomyces fermentation is subjected to solid-liquid separation, and the pre-purified liquid of nemoctine obtained after leaching has a purity of 18.2%, which contains 90 g of solids with a concentration of 1.8%, and is pumped into polyethersulfone hollow fiber microfiltration Membrane filtration, control pump pressure 0.1-0.7MP. The membrane filtrate was received to obtain a filtrate with a purity of 20%.

[0040] The above-mentioned filtrate is pumped into a roll-type ultrafiltration membrane with a molecular weight cut-off of 2000 for filtration, and the pump pressure is controlled at 0.7-1.2MP to receive the filtrate to obtain a filtrate with a purity of 52%.

[0041] (2) The nimoctine solution after ultrafiltration in step (1) is pumped into a roll-type nanofiltration membrane with a molecular weight cut off of 200 for conc...

Embodiment 3

[0048] The steps of the method for preparing high-purity moxictine in this embodiment are as follows:

[0049] (1) The fermented liquid produced by Streptomyces fermentation is subjected to solid-liquid separation, and the pre-purified liquid of nimoctine obtained after leaching has a purity of 13.2%, which contains 100 g of solids with a concentration of 1.4.8%, and is pumped into the polyethersulfone central control Fiber microfiltration membrane filtration, control pump pressure 0.1-0.7MP. The membrane filtrate was received to obtain a filtrate with a purity of 18.6%.

[0050] The above-mentioned filtrate is pumped into a roll-type ultrafiltration membrane with a molecular weight cut-off of 1500 for filtration, and the pump pressure is controlled at 0.7-1.2MP to receive the filtrate to obtain a filtrate with a purity of 51.4%.

[0051] (2) The nimoctine solution after ultrafiltration in step (1) is pumped into a roll-type nanofiltration membrane with a molecular weight cut...

technical field

[0001] The invention relates to the technical field of medicinal chemistry, in particular to a membrane separation preparation method for high-purity moxidectine. Background technique

[0002] Moxidectin (INN: Moxidectin) is a macrolide agricultural antibiotic, mainly used to treat parasitic diseases in animals such as cattle and sheep, and can be fermented by Streptomyces to produce Nemadectin (INN: Nemadectin) , and then obtained by chemical reaction, the structural formulas of nimoctine and moxictine are as formula (1).

[0003]

[0004] U.S. Patent No. 4916154A discloses a method for preparing moxictin, which involves solid-liquid separation of the fermented liquid produced by Streptomyces fermentation, extraction of the nimoctine solution obtained after leaching, silica gel column chromatography, gel layer Nemoctine obtained by analysis with a purity of more than 90% (HPLC), the purified nemoctine is obtained through up-protection, oxidation, deprote...

Examples

Embodiment 1

[0028] The steps of the method for preparing high-purity moxictine in this embodiment are as follows:

[0029] (1) The fermented liquid produced by Streptomyces fermentation undergoes solid-liquid separation, and the pre-purified liquid of nemoctine obtained after leaching has a purity of 15.6%, which contains 80 g of solids with a concentration of 1.5%, and is pumped into polyethersulfone hollow fiber microfiltration Membrane filtration, control pump pressure 0.1-0.7MP. The membrane filtrate was received to obtain a filtrate with a purity of 20%.

[0030] The above-mentioned filtrate is pumped into a roll-type ultrafiltration membrane with a molecular weight cut-off of 3000 for filtration, and the pump pressure is controlled at 0.5-0.9MP to receive the filtrate to obtain a filtrate with a purity of 52.5%.

[0031] (2) The nimoctine solution after ultrafiltration in step (1) is pumped into a roll-type nanofiltration membrane with a molecular weight cut off of 200 for concentr...

Embodiment 2

[0038] The steps of the method for preparing high-purity moxictine in this embodiment are as follows:

[0039] (1) The fermented liquid produced by Streptomyces fermentation is subjected to solid-liquid separation, and the pre-purified liquid of nemoctine obtained after leaching has a purity of 18.2%, which contains 90 g of solids with a concentration of 1.8%, and is pumped into polyethersulfone hollow fiber microfiltration Membrane filtration, control pump pressure 0.1-0.7MP. The membrane filtrate was received to obtain a filtrate with a purity of 20%.

[0040] The above-mentioned filtrate is pumped into a roll-type ultrafiltration membrane with a molecular weight cut-off of 2000 for filtration, and the pump pressure is controlled at 0.7-1.2MP to receive the filtrate to obtain a filtrate with a purity of 52%.

[0041] (2) The nimoctine solution after ultrafiltration in step (1) is pumped into a roll-type nanofiltration membrane with a molecular weight cut off of 200 for conc...

Embodiment 3

[0048] The steps of the method for preparing high-purity moxictine in this embodiment are as follows:

[0049] (1) The fermented liquid produced by Streptomyces fermentation is subjected to solid-liquid separation, and the pre-purified liquid of nimoctine obtained after leaching has a purity of 13.2%, which contains 100 g of solids with a concentration of 1.4.8%, and is pumped into the polyethersulfone central control Fiber microfiltration membrane filtration, control pump pressure 0.1-0.7MP. The membrane filtrate was received to obtain a filtrate with a purity of 18.6%.

[0050] The above-mentioned filtrate is pumped into a roll-type ultrafiltration membrane with a molecular weight cut-off of 1500 for filtration, and the pump pressure is controlled at 0.7-1.2MP to receive the filtrate to obtain a filtrate with a purity of 51.4%.

[0051] (2) The nimoctine solution after ultrafiltration in step (1) is pumped into a roll-type nanofiltration membrane with a molecular weight cut...

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