Sugammadex Sodium Turbidity and Visible Foreign Matter Removal Method

Abstract

The invention discloses a method for removing sugammadex sodium turbidity and visible foreign matter, comprising the following steps: taking an aqueous solution of sugammadex sodium, heating and stirring under the protection of an inert gas, and making the sugammadex sodium aqueous solution Substances causing turbidity and / or forming visible foreign matter are precipitated and filtered to remove turbidity and visible foreign matter from sugammadex sodium. The removal method of the present invention is simple and convenient to operate, low in cost, remarkable in removal effect, stable in product quality and can be applied industrially. The technical problems of sodium glucose clarity and visible foreign matter have improved the quality and safety of sugammadex sodium finished products.

Description

technical field

[0001] The invention belongs to the technical field of pharmacy, and relates to a method for removing sugammadex sodium turbidity and visible foreign matter, in particular to a method for removing turbidity and visible foreign matter of sugammadex sodium injection (aqueous solution of sugammadex sodium). removal method. Background technique

[0002] Sugammadex sodium is a derivative of γ-cyclodextrin, a selective muscle relaxant antagonist, which was first developed by Organon, which was acquired by Schering-Plough in 2007. ), and in 2009 Schering-Plough merged with Merck. Sugammadex Sodium is currently owned and sold by Merck, and the structure of its molecular compound is as follows:

[0003]

[0004] Sugammadex sodium, as an injection raw material, has a high solubility in water. In the prior art, the crystallization method of sugammadex sodium is mainly to drop a poor solvent into an aqueous solution of sugammadex sodium to precipitate sugammadex so...

Examples

Embodiment 1

[0031] A method for removing sugammadex sodium turbidity and visible foreign matter of the present invention, comprising the following steps:

[0032] Dissolve 10g of sugammadex sodium in 100mL of water for injection, adjust the pH to 7.5, heat up to 80°C under the protection of nitrogen and keep stirring for 5 hours at a stirring speed of 80r / min to cause the turbidity of sugammadex sodium by heating Precipitation and precipitation of substances and visible foreign matter, then lower the temperature to 25 ° C, and circulate and filter through a filter membrane with a pore size of 0.10 μm for 5 hours to obtain sugammadex sodium that removes turbidity and visible foreign matter. Pour 5mL of the obtained solution into the ampoule and sterilize at 121°C for 30min. Observation was carried out by a clarity detector, and the result was obtained: the obtained solution was clear and transparent, and the clarity was less than No. 0.5 turbidity standard solution, equivalent to purified ...

Embodiment 2

[0038] A method for removing sugammadex sodium turbidity and visible foreign matter of the present invention, comprising the following steps:

[0039] Dissolve 10g of sugammadex sodium in 90mL of water for injection, set the volume to 100mL, adjust the pH to 7.5, heat up to 80°C under nitrogen protection and keep stirring for 5 hours at a stirring speed of 150r / min, then cool down to 25°C, Circulate and filter through a filter membrane with a pore size of 0.10 μm for 5 hours to remove turbidity substances and visible foreign matter of sugammadex sodium. Pour 5mL of the obtained solution into the ampoule and sterilize at 121°C for 30min. Under the clarification instrument, it is clear and transparent, which is equivalent to purified water, without turbidity and opalescence. After the injection was left to stand at room temperature for 72 hours, the solution was still clear and transparent, comparable to purified water, and no white dot-like visible foreign matter was produced....

Embodiment 3

[0045] A method for removing sugammadex sodium turbidity and visible foreign matter of the present invention, comprising the following steps:

[0046] Dissolve 10g of sugammadex sodium in 100mL of water for injection, heat up to 85°C under nitrogen protection and keep stirring for 3 hours at a stirring speed of 120r / min, cool down to 25°C, and circulate and filter through a filter membrane with a pore size of 0.22μm 3 Hours, remove the turbidity and visible foreign matter of sugammadex sodium. Pour 5mL of the obtained solution into the ampoule and sterilize at 121°C for 30min. It is clear and transparent under the test of the clarification instrument, and the clarity is equivalent to that of purified water. There is no turbidity, opalescence, and no white point-like visible foreign matter.

[0047] The sugammadex sodium used in the present invention can be obtained by existing freeze-drying methods, but is not limited thereto:

[0048] Add 20 g of crude sugammadex sodium int...

technical field

[0001] The invention belongs to the technical field of pharmacy, and relates to a method for removing sugammadex sodium turbidity and visible foreign matter, in particular to a method for removing turbidity and visible foreign matter of sugammadex sodium injection (aqueous solution of sugammadex sodium). removal method. Background technique

[0002] Sugammadex sodium is a derivative of γ-cyclodextrin, a selective muscle relaxant antagonist, which was first developed by Organon, which was acquired by Schering-Plough in 2007. ), and in 2009 Schering-Plough merged with Merck. Sugammadex Sodium is currently owned and sold by Merck, and the structure of its molecular compound is as follows:

[0003]

[0004] Sugammadex sodium, as an injection raw material, has a high solubility in water. In the prior art, the crystallization method of sugammadex sodium is mainly to drop a poor solvent into an aqueous solution of sugammadex sodium to precipitate sugammadex so...

Examples

Embodiment 1

[0031] A method for removing sugammadex sodium turbidity and visible foreign matter of the present invention, comprising the following steps:

[0032] Dissolve 10g of sugammadex sodium in 100mL of water for injection, adjust the pH to 7.5, heat up to 80°C under the protection of nitrogen and keep stirring for 5 hours at a stirring speed of 80r / min to cause the turbidity of sugammadex sodium by heating Precipitation and precipitation of substances and visible foreign matter, then lower the temperature to 25 ° C, and circulate and filter through a filter membrane with a pore size of 0.10 μm for 5 hours to obtain sugammadex sodium that removes turbidity and visible foreign matter. Pour 5mL of the obtained solution into the ampoule and sterilize at 121°C for 30min. Observation was carried out by a clarity detector, and the result was obtained: the obtained solution was clear and transparent, and the clarity was less than No. 0.5 turbidity standard solution, equivalent to purified ...

Embodiment 2

[0038] A method for removing sugammadex sodium turbidity and visible foreign matter of the present invention, comprising the following steps:

[0039] Dissolve 10g of sugammadex sodium in 90mL of water for injection, set the volume to 100mL, adjust the pH to 7.5, heat up to 80°C under nitrogen protection and keep stirring for 5 hours at a stirring speed of 150r / min, then cool down to 25°C, Circulate and filter through a filter membrane with a pore size of 0.10 μm for 5 hours to remove turbidity substances and visible foreign matter of sugammadex sodium. Pour 5mL of the obtained solution into the ampoule and sterilize at 121°C for 30min. Under the clarification instrument, it is clear and transparent, which is equivalent to purified water, without turbidity and opalescence. After the injection was left to stand at room temperature for 72 hours, the solution was still clear and transparent, comparable to purified water, and no white dot-like visible foreign matter was produced....

Embodiment 3

[0045] A method for removing sugammadex sodium turbidity and visible foreign matter of the present invention, comprising the following steps:

[0046] Dissolve 10g of sugammadex sodium in 100mL of water for injection, heat up to 85°C under nitrogen protection and keep stirring for 3 hours at a stirring speed of 120r / min, cool down to 25°C, and circulate and filter through a filter membrane with a pore size of 0.22μm 3 Hours, remove the turbidity and visible foreign matter of sugammadex sodium. Pour 5mL of the obtained solution into the ampoule and sterilize at 121°C for 30min. It is clear and transparent under the test of the clarification instrument, and the clarity is equivalent to that of purified water. There is no turbidity, opalescence, and no white point-like visible foreign matter.

[0047] The sugammadex sodium used in the present invention can be obtained by existing freeze-drying methods, but is not limited thereto:

[0048] Add 20 g of crude sugammadex sodium int...

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