CN113004437B - Method for reducing solvent residue in sodium sugammadex - Google Patents
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- CN113004437B CN113004437B CN201911316243.5A CN201911316243A CN113004437B CN 113004437 B CN113004437 B CN 113004437B CN 201911316243 A CN201911316243 A CN 201911316243A CN 113004437 B CN113004437 B CN 113004437B
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
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- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
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- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
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- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
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Abstract
The invention relates to a method for reducing solvent residues in sodium sugammadex. The method adopts mild conditions to remove excessive uncontrollable solvent residues in the product, thereby achieving the purpose of controlling the quality of the product. Through technical improvement, in a closed container containing an aqueous medium, residual solvent in the product is replaced by utilizing moisture in the closed environment, so that the purpose of removing solvent residues is achieved. By adopting the technical scheme of the invention, the material drying condition (more than 100 ℃) at high temperature can be avoided, and the degradation of products under the condition of high temperature can be prevented; the unstable control of the dissolution residue of the high-temperature material drying process can be avoided; the technical scheme is simple to operate, and solvent residues are removed cleanly.
Description
Technical Field
The invention relates to a method for reducing solvent residues in sodium sugammadex, belonging to the field of pharmaceutical chemistry.
Background
Sodium sugammadex (trade name of brision, english name Sugammadex Sodium), chemical name sodium 6-perdeoxy-6-per (2-carboxyethyl) thio- γ -cyclodextrin. Sodium sulmore is an improved gamma-cyclodextrin, is a selective relaxation antagonist for reversing neuromuscular blocking agents, is clinically used for reversing neuromuscular blocking effects of rocuronium or vecuronium, and has good curative effect and safety. The drug is approved to be marketed in the European Union in month 7 of 2008, is marketed in japan, korea, the united states and the like, and is declared to be produced and marketed in China.
Sodium sugammadex is a large-ring molecular structure and is provided with a cavity, a plurality of exposed hydroxyl groups exist in the molecule, and the solvent molecules can form hydrogen bonds or directly wrap the solvent molecules in the cavity, so that the residual solvent is difficult to be controlled below the standard limit of ICH (International conference on the registration of human drugs) by the conventional reduced pressure distillation and drying means.
Disclosure of Invention
The invention aims to provide a method for reducing solvent residues in sodium sugammadex, which adopts mild conditions to remove excessive and uncontrollable solvent residues (higher than ICH limit) in products, so as to achieve the aim of controlling the product quality.
The inventor finds that under the condition of higher air humidity (the relative humidity is more than 75 percent) in the environment, sodium digluconate is left in the air for a certain time by adopting a direct volatilization method, the solvent residual quantity is reduced more, but the solvent residual quantity is reduced to be in accordance with the requirement and is difficult to determine, and when the air humidity is lower, the solvent residual quantity is reduced slightly, but the solvent residual quality requirement is difficult to reach; in addition, in the direct volatilization method, the ambient humidity is difficult to control, which is unfavorable for operation and control.
Through technical improvement, the invention can achieve the purpose of removing solvent residues by utilizing moisture in the closed environment to replace residual solvent in the product in the closed container containing the aqueous medium. By adopting the technical scheme of the invention, the material drying condition (more than 100 ℃) at high temperature can be avoided, and the degradation of products under the condition of high temperature can be prevented; the unstable control of solvent residue in the high-temperature material drying process or direct volatilization and other methods can be avoided; the technical scheme is simple to operate, and solvent residues are removed cleanly.
The invention provides a method for reducing solvent residues in sodium sugammadex, which comprises the following steps: the sodium sulmore gluconate is placed in a closed container containing an aqueous medium and the moisture in the closed environment is used for replacing the residual solvent in the sodium sulmore gluconate. The method is simple to operate, avoids high-temperature conditions, and can effectively prevent sodium gluconate from being degraded.
The residual solvent which can be reduced in the invention comprises one or more of methanol, ethanol, isopropanol, n-butanol, acetonitrile and acetone. In some embodiments, the residual solvent that can be reduced comprises methanol; in some embodiments, the residual solvent that can be reduced comprises ethanol; in some embodiments, the residual solvent that can be reduced comprises acetonitrile; in some embodiments, the residual solvent that can be reduced comprises acetone.
In some embodiments, the aqueous medium comprises water, a brine solution, or an inert gas that contains water. In some embodiments, the aqueous medium is water. In some embodiments, the aqueous medium is a brine solution. In some embodiments, the aqueous medium is aqueous wet nitrogen. In some embodiments, the aqueous medium is aqueous wet carbon dioxide. In some embodiments, the aqueous medium is aqueous wet argon.
In some embodiments, the aqueous medium is water, the temperature of which is from 20 ℃ to 100 ℃, or from 20 ℃ to 75 ℃, or from 75 ℃ to 100 ℃. In some embodiments, the temperature of the water is 20 ℃ to 45 ℃; in some embodiments, the temperature of the water is 45 ℃ to 75 ℃; in some embodiments, the temperature of the water is 45 ℃ to 100 ℃. In some embodiments, the temperature of the water is 20 ℃,45 ℃,75 ℃, or 100 ℃.
In some embodiments, sodium supreme is spread open in the trays and the moisture in the system is slowly displaced by the moisture in the air. The moisture content in the environment is 20% -100%. In some embodiments, the moisture in the environment ranges from 70% to 95%.
In some embodiments, sodium metasedge is mixed with an amount of water (1% -500%), and the solvent in the sodium metasedge is replaced by the added water.
In some embodiments, the purpose of displacing residual solvent in the product is achieved by continuously introducing an inert gas containing water into a dryer containing sodium supreme.
In some embodiments, the purpose of displacing residual solvent in the product is achieved by continuously introducing wet nitrogen or wet carbon dioxide or wet argon into a dryer containing sodium supreme gluconate.
In some embodiments, the aqueous salt solution comprises a saturated aqueous salt solution or an unsaturated aqueous salt solution. In some embodiments, the aqueous salt solution is a saturated aqueous salt solution. In some embodiments, the brine solution is an unsaturated brine solution.
In some embodiments, the brine solution includes at least one selected from the group consisting of aqueous potassium chloride, aqueous potassium bromide, aqueous sodium chloride, aqueous sodium nitrate, aqueous potassium nitrate, aqueous sodium bromide, aqueous lithium acetate, aqueous ammonium sulfate, aqueous sodium benzoate, aqueous potassium sulfate, and aqueous disodium hydrogen phosphate. In some embodiments, the brine solution is an aqueous potassium chloride solution. In some embodiments, the brine solution is an aqueous potassium bromide solution. In some embodiments, the brine solution is an aqueous sodium chloride solution.
In some embodiments, the saturated brine solution includes at least one selected from the group consisting of a saturated aqueous potassium chloride solution, a saturated aqueous potassium bromide solution, a saturated aqueous sodium chloride solution, a saturated aqueous sodium nitrate solution, a saturated aqueous potassium nitrate solution, a saturated aqueous sodium bromide solution, a saturated aqueous lithium acetate solution, a saturated aqueous ammonium sulfate solution, a saturated aqueous sodium benzoate solution, a saturated aqueous potassium sulfate solution, and a saturated aqueous disodium hydrogen phosphate solution. In some embodiments, the brine solution is a saturated aqueous solution of potassium chloride. In some embodiments, the brine solution is a saturated aqueous solution of potassium bromide. In some embodiments, the brine solution is a saturated aqueous solution of sodium chloride.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sugammadex in a closed container containing a saturated aqueous solution of potassium chloride, and replacing ethanol or methanol residues in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sugammadex in a closed container containing potassium bromide saturated aqueous solution, and replacing ethanol or methanol residues in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sugammadex in a closed container containing saturated aqueous solution of sodium chloride, and replacing ethanol or methanol residues in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sugammadex in a closed container containing sodium nitrate saturated aqueous solution, and replacing ethanol or methanol residues in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sugammadex in a closed container containing a saturated aqueous solution of potassium nitrate, and replacing ethanol or methanol residues in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sugammadex in a closed container containing sodium bromide saturated aqueous solution, and replacing ethanol or methanol residues in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sugammadex in a closed container containing a saturated aqueous solution of lithium acetate, and replacing ethanol or methanol residues in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sugammadex in a closed container containing an ammonium sulfate saturated aqueous solution, and replacing ethanol or methanol residues in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium suger in a closed container containing a saturated aqueous solution of sodium benzoate, and replacing ethanol or methanol residues in the sodium suger by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium digluconate in a closed container containing a saturated aqueous solution of disodium hydrogen phosphate, and replacing ethanol or methanol residues in the sodium digluconate by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: and placing sodium sulmore in a closed container containing a saturated aqueous solution of potassium sulfate, and replacing ethanol, methanol, acetonitrile or acetone residues in the sodium sulmore by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: placing the sodium sugammadex in a closed container containing hot water at 75 ℃, and replacing residual ethanol or residual methanol in the sodium sugammadex by utilizing moisture in the closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: placing the sodium sugammadex in a closed container containing water at 20 ℃, and replacing residual ethanol or residual methanol in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: placing the sodium sugammadex in a closed container containing hot water at 45 ℃, and replacing residual ethanol or residual methanol in the sodium sugammadex by utilizing moisture in a closed environment.
In some embodiments, a method of reducing solvent residue in sodium supreme comprising: placing the sodium sugammadex in a closed container containing hot water at 100 ℃, and replacing residual ethanol or residual methanol in the sodium sugammadex by utilizing moisture in a closed environment.
The method for reducing solvent residues in sodium sulmore comprises the step of reducing solvent residues in sodium sulmore, wherein the dosage of the aqueous medium is 80-250ml per 1g of sodium sulmore.
Definition of terms
The invention is intended to cover all alternatives, modifications and equivalents, which may be included within the scope of the invention as defined by the appended claims. Those skilled in the art will recognize that many methods and materials similar or equivalent to those described herein can be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described herein. In the event of one or more of the incorporated references, patents and similar materials differing from or contradictory to the present application (including but not limited to defined terms, term application, described techniques, etc.), the present application controls.
It should further be appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference in their entirety.
The terms "comprising" or "including" are used in an open-ended fashion, i.e., including the teachings described herein, but not excluding additional aspects.
In the context of the present invention, all numbers disclosed herein are approximate, whether or not the word "about" or "about" is used. The numerical value of each number may vary by less than 10% or reasonably as considered by those skilled in the art, such as 1%, 2%, 3%, 4% or 5%.
In the invention, the DEG C refers to the DEG C; m refers to rice; mm means millimeter; cm means cm; μm refers to micrometers; mg refers to milligrams; mL refers to milliliters; the method comprises the steps of carrying out a first treatment on the surface of the h means hours; min means minutes; hz refers to hertz; ppm refers to parts per million (1 ppm = parts per million); DMSO refers to dimethyl sulfoxide.
Detailed Description
In order to better understand the technical solution of the present invention, the following non-limiting examples are further disclosed for further details of the present invention.
The reagents used in the present invention are all commercially available or can be prepared by the methods described herein.
Instrument parameters, test conditions and characterization results
Instrument information:
gas chromatograph-Agilent 7890A-7697A
Method for measuring solvent residue
TABLE 1 chromatographic method for solvent residual test of sodium sulmore gluconate
The following example used the same crude sodium gullet. The loss on drying under reduced pressure is 10% or less, and the residual moisture may be as high as 10% depending on the nature of the product.
Example 1
A saturated aqueous solution of potassium chloride was prepared, 1000-1700ml of the saturated aqueous solution of potassium chloride was placed in a desiccator having a diameter of 25-30cm (ensuring that the liquid level of the solution was not higher than that of the sample), and equilibrated for 5-16 hours until the humidity was constant. After placing 10g of the crude sodium sulmore in a dryer for 48 hours, transferring the sample into a decompression drying box, and decompressing and drying at 75 ℃ for 24 hours until the drying weight is less than 10%.
Example 2
A saturated aqueous solution of potassium bromide was prepared, 1000-1700ml of the saturated aqueous solution of potassium bromide was placed in a desiccator having a diameter of 25-30cm (ensuring that the liquid level of the solution was not higher than that of the sample), and equilibrated for 5-16 hours until the humidity was constant. After placing 10g of sodium supreme glucose in a dryer for 48 hours, the sample is transferred to a decompression drying box and decompressed and dried for 24 hours at 75 ℃ until the drying weight is less than 10%.
Example 3
A saturated aqueous solution of sodium chloride was prepared, 1000-1700ml of the saturated aqueous solution of sodium chloride was placed in a desiccator having a diameter of 25-30cm (ensuring that the liquid level of the solution was not higher than that of the sample), and equilibrated for 5-16 hours until the humidity was constant. After placing 10g of sodium supreme glucose in a dryer for 48 hours, the sample is transferred to a decompression drying box and decompressed and dried for 24 hours at 75 ℃ until the drying weight is less than 10%.
Example 4
A saturated aqueous solution of sodium bromide was prepared, 1000-1700ml of the saturated aqueous solution of sodium bromide was placed in a desiccator having a diameter of 25-30cm (ensuring that the liquid level of the solution was not higher than that of the sample), and equilibrated for 5-16 hours until the humidity was constant. After placing 10g of sodium supreme glucose in a dryer for 5 days, the sample is transferred to a reduced pressure drying box and dried under reduced pressure at 75 ℃ for 24 hours until the drying weight is less than 10%.
Example 5
Preparing a saturated aqueous solution of lithium acetate, placing 1000-1700ml of the saturated aqueous solution of lithium acetate into a drier with the diameter of 25-30cm (ensuring that the liquid level of the solution is not higher than that of a sample), and balancing for 5-16h until the humidity is constant. After placing 10g of sodium supreme glucose in a dryer for 3 days, the sample is transferred to a decompression drying box and decompressed and dried for 24 hours at 75 ℃ until the drying weight is less than 10%.
Example 6
An ammonium sulfate saturated aqueous solution was prepared, 1000-1700ml of the ammonium sulfate saturated aqueous solution was placed in a desiccator having a diameter of 25-30cm (ensuring that the liquid level of the solution was not higher than that of the sample), and the equilibrium was maintained for 5-16 hours until the humidity was constant. After placing 10g of sodium supreme glucose in a dryer for 24 hours, the sample is transferred to a decompression drying box and decompressed and dried at 75 ℃ for 24 hours until the drying weight is less than 10%.
Example 7
Preparing saturated aqueous solution of sodium benzoate, placing 1000-1700ml of saturated aqueous solution of sodium benzoate in a drier with diameter of 25-30cm (ensuring that the liquid level of the solution is not higher than that of the sample), and balancing for 5-16h until humidity is constant. After placing 10g of sodium supreme glucose in a dryer for 24 hours, the sample is transferred to a decompression drying box and decompressed and dried at 75 ℃ for 24 hours until the drying weight is less than 10%.
Example 8
A saturated aqueous solution of potassium nitrate was prepared, 1000-1700ml of the saturated aqueous solution of potassium nitrate was placed in a desiccator having a diameter of 25-30cm (ensuring that the liquid level of the solution was not higher than that of the sample), and the equilibrium was maintained for 5-16 hours until the humidity was constant. After placing 10g of sodium supreme glucose in a dryer for 24 hours, the sample is transferred to a decompression drying box and decompressed and dried at 75 ℃ for 24 hours until the drying weight is less than 10%.
Example 9
Preparing a saturated aqueous solution of disodium hydrogen phosphate, placing 1000-1700ml of the saturated aqueous solution of disodium hydrogen phosphate into a dryer with the diameter of 25-30cm (ensuring that the liquid level of the solution is not higher than that of a sample), and balancing for 5-16h until the humidity is constant. After placing 10g of sodium supreme glucose in a dryer for 24 hours, the sample is transferred to a decompression drying box and decompressed and dried at 75 ℃ for 24 hours until the drying weight is less than 10%.
Example 10
Preparing saturated aqueous solution of potassium sulfate, placing 1000-1700ml of saturated aqueous solution of potassium sulfate into a drier with the diameter of 25-30cm (ensuring that the liquid level of the solution is not higher than that of a sample), and balancing for 5-16h until the humidity is constant. After placing 10g of sodium supreme glucose in a dryer for 24 hours, the sample is transferred to a decompression drying box and decompressed and dried at 75 ℃ for 24 hours until the drying weight is less than 10%.
Example 11
Preparing saturated aqueous solution of potassium sulfate, placing 1000-1700ml of saturated aqueous solution of potassium sulfate into a drier with the diameter of 25-30cm (ensuring that the liquid level of the solution is not higher than that of a sample), and balancing for 5-16h until the humidity is constant. After placing 10g of sodium supreme glucose in a dryer for 48 hours, the sample is transferred to a decompression drying box and decompressed and dried for 24 hours at 75 ℃ until the drying weight is less than 10%.
Example 12
Adding 800-1000ml of hot water at 75 ℃ into a 25-30cm dryer (ensuring that the liquid level of the hot water is not higher than that of a sample), paving 10g of sodium sugammadex sample into a material tray in the dryer, sealing, standing for 9h, transferring the sample into a decompression drying box, decompressing and drying at 75 ℃ for 24h until the loss of weight is less than 10%.
Example 13
Adding 800-1000ml of water at 20 ℃ into a 25-30cm dryer (ensuring that the liquid level of the water is not higher than that of a sample), paving 5g of sodium sugammadex sample into a material tray in the dryer, sealing, standing for 7 days, transferring the sample into a decompression drying box, decompressing and drying at 75 ℃ for 24 hours until the weight loss is less than 10%.
Example 14
Adding 800-1000ml of 45 ℃ hot water (ensuring that the liquid level of the hot water is not higher than that of a sample) into a 25-30cm dryer, paving 5g of sodium sugammadex sample in a material tray in the dryer, sealing, placing the dryer in an oil bath at 45 ℃ for 16 hours, transferring the sample into a decompression drying box, decompressing and drying at 75 ℃ for 24 hours until the drying weight is less than 10%.
Example 15
Adding 800-1000ml of hot water at 100 ℃ into a 25-30cm dryer (ensuring that the liquid level of the hot water is not higher than that of a sample), paving 5g of sodium sugammadex sample into a material tray in the dryer, sealing, changing the hot water every 15min, standing for 3h, transferring the sample into a decompression drying box, decompressing and drying at 75 ℃ for 24h until the weight loss is less than 10%.
The results of the determination of solvent residues for crude sodium digluconate and the products of examples 1-15 are shown in tables 2-4.
Table 2 results of the ethanol residue determination of sodium sulmore gluconate product in examples
Table 3 results of acetonitrile and acetone residue measurements of crude sodium sulmore gluconate and products of the examples
Table 4 determination of the methanol residue of crude sodium Shuganglucose and products in the examples
As can be seen from tables 2 to 4, the residual solvent in sodium sulmore is replaced by the moisture in the closed environment by placing the sodium sulmore bulk drug in the closed container containing the aqueous medium, and the effect of effectively reducing the solvent residue can be achieved.
While the methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations and combinations of the methods and applications described herein can be made and applied within the spirit and scope of the invention. Those skilled in the art can, with the benefit of this disclosure, suitably modify the process parameters to achieve this. It is expressly noted that all such similar substitutions and modifications will be apparent to those skilled in the art, and are deemed to be included within the present invention.
Claims (8)
1. A method for reducing solvent residue in sodium supreme comprising: placing the sodium suger in a closed container containing an aqueous medium, and replacing residual solvent in the sodium suger by utilizing moisture in the closed environment; the solvent comprises one or more of methanol, ethanol, isopropanol, n-butanol, acetonitrile and acetone; the aqueous medium is water or saline solution, and the dosage of the aqueous medium is 80-250mL per 1g sodium digluconate which needs to reduce solvent residue.
2. The method of claim 1, wherein the aqueous medium is water and the temperature of the water is from 20 ℃ to 100 ℃.
3. The method of claim 2, wherein the temperature of the water is 75 ℃.
4. The method of claim 2, wherein the temperature of the water is 45 ℃.
5. The method of claim 1, wherein the brine solution comprises a saturated brine solution or an unsaturated brine solution.
6. The method of claim 1 or 5, wherein the brine solution comprises at least one selected from the group consisting of aqueous potassium chloride, aqueous potassium bromide, aqueous sodium chloride, aqueous sodium nitrate, aqueous potassium nitrate, aqueous sodium bromide, aqueous lithium acetate, aqueous ammonium sulfate, aqueous sodium benzoate, aqueous potassium sulfate, and aqueous disodium hydrogen phosphate.
7. The method according to claim 5, wherein the saturated brine solution comprises at least one selected from the group consisting of a saturated aqueous potassium chloride solution, a saturated aqueous potassium bromide solution, a saturated aqueous sodium chloride solution, a saturated aqueous sodium nitrate solution, a saturated aqueous potassium nitrate solution, a saturated aqueous sodium bromide solution, a saturated aqueous lithium acetate solution, a saturated aqueous ammonium sulfate solution, a saturated aqueous sodium benzoate solution, a saturated aqueous potassium sulfate solution, and a saturated aqueous disodium hydrogen phosphate solution.
8. The method according to claim 1, characterized in that it comprises: placing the sodium sulmore glucose in a closed container containing a potassium chloride saturated aqueous solution or a sodium chloride saturated aqueous solution, and replacing residual ethanol or residual methanol in the sodium sulmore glucose by utilizing moisture in a closed environment; or comprises: placing the sodium suger in a closed container containing hot water at 45 ℃, and replacing residual methanol in the sodium suger by utilizing moisture in a closed environment; or comprises: placing the sodium sugammadex in a closed container containing a saturated aqueous solution of potassium sulfate, and replacing acetonitrile or acetone remained in the sodium sugammadex by utilizing moisture in a closed environment; or comprises: the sodium sugammadex is placed in a closed container containing hot water at 75 ℃ and the residual ethanol in the sodium sugammadex is replaced by the moisture in the closed environment.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103145875A (en) * | 2012-12-07 | 2013-06-12 | 青岛九龙生物医药有限公司 | Technique of reducing organic solvent residue in heparin sodium |
| CN105348412A (en) * | 2014-08-22 | 2016-02-24 | 江苏恩华药业股份有限公司 | Method for purifying sugammadex sodium |
| CN108929389A (en) * | 2017-05-23 | 2018-12-04 | 合肥博思科创医药科技有限公司 | A kind of environmentally protective easypro more glucose sodium preparation method |
| CN109021147A (en) * | 2017-06-08 | 2018-12-18 | 天津科伦药物研究有限公司 | A kind of purification process for the more glucose sodium that relaxes |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145875A (en) * | 2012-12-07 | 2013-06-12 | 青岛九龙生物医药有限公司 | Technique of reducing organic solvent residue in heparin sodium |
| CN105348412A (en) * | 2014-08-22 | 2016-02-24 | 江苏恩华药业股份有限公司 | Method for purifying sugammadex sodium |
| CN108929389A (en) * | 2017-05-23 | 2018-12-04 | 合肥博思科创医药科技有限公司 | A kind of environmentally protective easypro more glucose sodium preparation method |
| CN109021147A (en) * | 2017-06-08 | 2018-12-18 | 天津科伦药物研究有限公司 | A kind of purification process for the more glucose sodium that relaxes |
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