CN111518229B

CN111518229B - Method for removing element impurities and pigments in refined sugammadex sodium product

Info

Publication number: CN111518229B
Application number: CN202010440236.2A
Authority: CN
Inventors: 潘攀; 郭辉; 吴友灵
Original assignee: Hefei Bosikc Pharmtech Co Ltd
Current assignee: Hefei Bosikc Pharmtech Co Ltd
Priority date: 2020-05-22
Filing date: 2020-05-22
Publication date: 2021-02-26
Anticipated expiration: 2040-05-22
Also published as: WO2021233125A1; CN111518229A

Abstract

The invention discloses a method for removing element impurities and pigments in refined sugammadex sodium products, which comprises the following steps: dissolving refined sugammadex sodium product in water solution, dripping certain amount of poor solvent to separate out small amount of sugammadex sodium, most of element impurity and pigment, separating the separated matter, collecting sugammadex sodium in the upper layer mother liquid, and direct concentration or solvent crystallization to obtain the product without most of element impurity. The obtained product has light color, the content of the element impurities is obviously reduced, the method meets the requirement of ICH on the limit of the element impurities, and the method has simple, convenient and safe operation, good economy and is suitable for industrial production.

Description

Method for removing element impurities and pigments in refined sugammadex sodium product

Technical Field

The invention relates to the technical field of medicine production and purification, in particular to a method for removing element impurities and pigments in refined sugammadex sodium.

Background

The chemical name of the sugammadex sodium is 6A,6B,6C,6D,6E,7F,6G, 6H-octa-S- (2-carboxyethyl) -6A,6B,6C,6D,6E,7F,6G, 6H-octathio-gamma-cyclodextrin octasodium salt, and the structural formula is as follows:

the sugammadex sodium is a novel muscle relaxant reversal agent developed by Organon corporation in the Netherlands, is clinically used for reversing the neuromuscular blockade effect of rocuronium bromide or vecuronium bromide, has good curative effect and has excellent safety. Since the european union approved for marketing in 2008, 7 months, it was marketed in japan, korea, the united states, etc., and in 2018, it was marketed in china.

The sugammadex sodium is gamma-cyclodextrin modified by a structure, small molecular impurities are easily wrapped in a cavity due to the hollow cavity structure of the sugammadex sodium, and a plurality of exposed polar groups such as hydroxyl, carboxyl and the like in the structure have a strong chelating effect on metal elements. Therefore, if excessive elemental impurities are introduced during the production of the product due to the material of the equipment, the raw materials, etc., it is difficult to remove by conventional means. This property presents a significant challenge to the formulation of a strategy for controlling the elemental impurities of sugammadex sodium. Moreover, the color of the sugammadex injection of the preparation product is deepened due to the existence of metal elements such as iron and the like, and in addition, some pigment substances such as humin and the like are not easily removed from the product under the chelation of the sugammadex molecules, so that the color control of the product is also challenged.

The research and control of the element impurities are the key focus fields of the current regulatory agencies on the full evaluation of the medicine quality research, and are also the key points of the medicine production process which need to be focused. At present, common methods for removing element impurities in the production of medicines, including the use of resin adsorption, silica gel adsorption, chelating agents and the like with specific models, have the problems of high cost, complex treatment process, solid waste generation and the like; the conventional simple recrystallization method is influenced by the special molecular structure of the sugammadex sodium, so that impurities wrapped and chelated on the sugammadex sodium molecule are difficult to remove; the purified water washing method cannot be applied to the better water-soluble substance of sugammadex sodium. The preparation process of sugammadex sodium and the purification process of related substances are reported more at home and abroad, but reports about the removal of element impurities and pigments are rare. Therefore, the method for efficiently and conveniently removing the element impurities in the sugammadex sodium is developed, and has important application value.

J.Med.chem.2002,45, 1806-one 1816PP proposes that under the catalysis of triphenylphosphine in an N, N-dimethylformamide system, bromine reacts with gamma-cyclodextrin to obtain 6-deoxy-6-perbromo-gamma-cyclodextrin. The product reacts with 3-mercaptopropionic acid methyl ester under the catalysis of anhydrous cesium carbonate to obtain a product sugammadex methyl ester, and the sugammadex sodium is obtained by hydrolysis through sodium hydroxide. The yield thereof was found to be 60%. The crude product of the sugammadex sodium obtained by the method has low purity, and no report of further refining, purifying and removing element impurities and pigments is provided.

Chem.asian J.2011,6, 2390-. Finally, the target product is obtained by forming ether with 3-mercaptopropionic acid. The reaction intermediate has high purity, less impurities and simple post-treatment and purification of the product. However, the risk of introducing elemental impurities associated with strongly basic reaction systems is not considered.

WO0140316PP uses iodine as a halogenating agent to react with gamma-cyclodextrin under the catalysis of triphenylphosphine to generate 6-deoxy-6-full iodo-gamma-cyclodextrin. The intermediate and 3-mercaptopropionic acid are synthesized into thioether, and a target product is obtained after membrane dialysis and purification. The method has simple and reliable route and higher reaction activity, but the purification of the product only adopts membrane dialysis purification, so the difficulty for obtaining high-purity sugammadex sodium is higher, and no report of further refining, purifying and removing element impurities and pigments is provided.

CN105348412 discloses a purification method of a sugammadex sodium crude product, which comprises hydrolyzing the sugammadex sodium crude product under an acidic condition to obtain a free acid solid, pulping the free acid solid, washing and purifying the free acid solid; reacting free acid with organic amine to prepare the sugammadex ammonium salt, and recrystallizing and purifying the obtained ammonium salt; and dissociating under an acidic condition to obtain free acid, pulping, washing and purifying the free acid solid water, and reacting the obtained free acid with sodium hydroxide to prepare the sugammadex sodium pure product. The method does not use column chromatography, dialysis and other methods, but has complex steps, needs to convert between free acid and salt for many times and is inconvenient to operate. In addition, the risk of introducing more elemental impurities in the elementary iodine of mineral origin and in the industrial production of strongly basic reaction systems is not taken into account.

Disclosure of Invention

The invention aims to solve the defects in the prior art and provides a method for removing element impurities and pigments in refined sugammadex sodium.

In order to achieve the purpose, the invention adopts the following two basically similar technical schemes:

the first scheme is as follows:

a method for removing element impurities and pigments in refined sugammadex sodium products comprises the following steps:

the method comprises the following steps: dissolving the refined sugammadex sodium product in water to form a clear solution, and adding a certain amount of poor solvent A at room temperature to turn the solution into a slightly turbid state; transferring the slightly turbid solution to a separating funnel, standing for layering, and allowing a small amount of oily matter to settle at the bottom; separating to obtain lower oily matter B and upper clear liquid C;

step two: transferring the supernatant C into a flask, and concentrating under reduced pressure to dryness to obtain the finished product E of sugammadex sodium with elemental impurities and pigments removed.

Preferably, the poor solvent a is specifically any one of acetone, methanol, ethanol, isopropanol, acetonitrile, 1, 4-dioxane, DMF, and DMSO.

Preferably, the mass ratio of the refined sugammadex sodium product to water in the first step is 1: 0.5-1: 50, and the mass ratio of the water to the poor solvent A is 1: 0.1-1: 50.

Further, the mass ratio of the refined sugammadex sodium product to water in the first step is 1: 1-1: 10, and the mass ratio of the water to the poor solvent A is 1: 1-1: 10.

More preferably, the mass ratio of the sugammadex sodium refined product to water in the first step is 1: 3-1: 4, and the mass ratio of the water to the poor solvent A is 1: 0.5-1: 1.

Scheme II:

step two: transferring the supernatant C into a flask, stirring at room temperature, adding a certain amount of poor solvent D while stirring, separating out white solid, filtering, and drying to obtain the finished product E of the sugammadex sodium with element impurities and pigments removed.

Preferably, the poor solvent a is specifically any one of acetone, methanol, ethanol, isopropanol, acetonitrile, 1, 4-dioxane, DMF, and DMSO, and the poor solvent D is specifically any one of acetone, methanol, ethanol, isopropanol, acetonitrile, 1, 4-dioxane, DMF, and DMSO.

Preferably, the mass ratio of the refined sugammadex sodium product to water in the first step is 1: 0.5-1: 50, and the mass ratio of the water to the poor solvent A is 1: 0.1-1: 50; in the second step, the mass ratio of the supernatant C to the poor solvent D is 1: 0.5-1: 50.

Further, the mass ratio of the refined product of sugammadex sodium to water in the first step is 1: 1-1: 10, and the mass ratio of the water to the poor solvent A is 1: 1-1: 10; in the second step, the mass ratio of the supernatant C to the poor solvent D is 1: 1-1: 10.

More preferably, the mass ratio of the refined sugammadex sodium product to water in the first step is 1: 3-1: 4, and the mass ratio of the water to the poor solvent A is 1: 0.5-1: 1; in the second step, the mass ratio of the supernatant C to the poor solvent D is 1: 2-1: 4.

Obviously, the difference between the scheme I and the scheme II lies in the treatment mode of the step II, the scheme I adopts a direct concentration method of supernatant C, the scheme II adopts a crystallization method of adding a poor solvent D, the scheme I has the advantage of saving organic solvent, and the scheme II has the advantages of high treatment speed and large batch size; the two schemes are slightly different in the removal rate of element impurities and pigments.

Compared with the prior art, the invention has the beneficial effects that:

1. the method adopts the poor solvent to be added into the sugammadex sodium aqueous solution, utilizes the capture and chelation between the sugammadex molecules with large-scale cavity structures and multi-site hydroxyl and carboxyl, metallic element impurities and pigments, separates out a small amount of sugammadex sodium and most of the element impurities and pigments from the solution by adding the poor solvent, and then adds the poor solvent or directly concentrates and dries the mother solution to obtain the product, thereby reducing the content of the element impurities in the refined sugammadex sodium product and lightening the color of the product.

2. The refined sugammadex sodium product is treated by the method, so that the content of element impurities in the refined sugammadex sodium product can be effectively reduced. Wherein the content of the iron element can be less than or equal to 10ppm, the content of the metal element impurities of the 1 st type and the metal element impurities of the 2A type can be less than or equal to 1ppm, the quality of the product meets the quality requirement of the injection raw material, the related technical requirement of the technical guidance principle ICH of European Union quality research is also met, and the high-quality raw material is provided for the production of the sugammadex injection.

3. The method for removing the element impurities and the pigment has the advantages of simple process, low cost, easy operation of the process, good economy and more suitability for industrial production; the preparation prepared from the raw materials has low element impurities, almost colorless product solution and good safety, avoids the influence of iron element on the color of the preparation to the maximum extent, reduces the toxicity risk caused by the element impurities, and brings the maximum benefit to patients.

Drawings

FIG. 1 is a HPLC chart of refined sugammadex sodium as a raw material used before the treatment of the present invention;

FIG. 2 is an ICP-MS report of refined sugammadex, the starting material used prior to the treatment of the present invention;

FIG. 3 is an HPLC plot of sugammadex sodium product after water/acetone treatment;

FIG. 4 is an ICP-MS report of sugammadex sodium product after water/acetone treatment;

FIG. 5 is an ICP-MS report of the oil obtained after water/acetone treatment;

FIG. 6 is an HPLC chart of sugammadex sodium product after water/DMF treatment;

FIG. 7 is an ICP-MS report of sugammadex sodium product after water/DMF treatment;

FIG. 8 is an HPLC plot of the sugammadex sodium product after water/acetonitrile/ethanol treatment;

FIG. 9 is an ICP-MS report of sugammadex sodium product after water/acetonitrile/ethanol treatment;

FIG. 10 is an HPLC plot of the sugammadex sodium product after water/ethanol/methanol treatment;

FIG. 11 is an ICP-MS report of sugammadex sodium product after water/ethanol/methanol treatment;

FIG. 12 is an HPLC chart of sugammadex sodium product after water/1, 4-dioxane treatment;

FIG. 13 is an ICP-MS report of sugammadex sodium product after water/1, 4-dioxane treatment;

FIG. 14 is an HPLC plot of sugammadex sodium product after water/DMF/DMSO treatment;

FIG. 15 is an ICP-MS report of sugammadex sodium product after water/DMF/DMSO treatment.

Detailed Description

Preferred embodiments of the process of the present invention are described in more detail below. It should be properly understood that: the methods of the present invention are illustrated in the examples and are not intended to be limiting, and therefore, the present invention is not limited to the modifications and variations of the methods of the present invention.

In the present invention, reagents, instruments and equipment are commercially available unless otherwise specified.

Method for determining purity by HPLC:

placing a sample to be tested in a 25ml volumetric flask, adding a small amount of water, shaking for dissolution, adding a solvent for dilution to a scale, and shaking uniformly to obtain a sample solution; precisely measuring 1ml of the solution, placing the solution in a 100ml volumetric flask, adding a solvent to dilute the solution to a scale, and shaking up the solution to be used as a reference solution; according to the chromatographic conditions under the content determination item (octadecylsilane chemically bonded silica is used as a filling agent, phosphate buffer is used as a mobile phase A, acetonitrile is used as a mobile phase B, linear gradient elution is carried out, the detection wavelength is 200nm), 20 mu l of a reference solution is injected into a liquid chromatograph, the sensitivity of the detector is adjusted, the peak height of a main component chromatographic peak is 10-25% of the full range, 20 mu l of a sample solution and 20 mu l of the reference solution are precisely measured, the sample solution and the reference solution are respectively injected into the liquid chromatograph, the chromatogram is recorded until the retention time of the main component peak is 3 times, and the sum of the peak area percentages of 6-octa- (2-carboxyethyl) thio-gamma-cyclodextrin sodium salt and 6-hepta- (2-carboxyethyl) thio-gamma-cyclodextrin sodium salt is the purity of a sample.

ICP-MS method for determining elemental impurities:

mode (2): the mode of the KED is set to,

timing (time control): sweets/reading 20, reading/copying 1, copies 3, Helium Flow 3.5.

Processing: detector, Dual; process spectral peak, Average; QID, On; isotope Ratio Mode, Off; blank bypass (Blank subtracted), After Internal standard test, After the After air Internal Std; process signal profile, Average; measurement Unit, cps; baseline Readings, 0; appliance smoothening Factor, 5. Sampling (sample introduction)

	Time (Time)	Speed (+/-rpm)
			Sample Flush (Sample Flush)	0	-42.0
Read Delay (Read Delay)	50	-35.0
			Analysis (Analysis)		-35.0
Wash (flushing)	0	-42.0

The refined sugammadex sodium products used in the examples are all products of the same batch, and the HPLC purity is as follows: 99.80% (FIG. 1), the sample was pale yellow, and measured by ICP-MS, wherein the Fe content was 113ppm, the Ti content was 6.3ppm, the Cr content was 6.4ppm, and the Co content was 1.1ppm (FIG. 2).

Example 1:

100g of refined sugammadex sodium product is taken, 300g of water is added to be dissolved to be clear, 190g of acetone is added at room temperature under stirring, and the solution turns to be slightly turbid after the addition is finished. The solution was transferred to a separatory funnel and allowed to stand for separation, leaving an orange-yellow oil to settle to the bottom. The oil was separated. Transferring the supernatant to a flask, stirring at room temperature, adding 1300g of acetone, separating out white solid, performing suction filtration, and drying to obtain 83g of white solid, namely sugammadex sodium, wherein the purity of the white solid is 99.78% by HPLC (high performance liquid chromatography) (shown in figure 3), and the purity of the product is not obviously changed. The Fe content was 4.1ppm by ICP-MS measurement, and the remaining elemental impurities were less than 1ppm (FIG. 4). The orange-yellow oil was tested and had a Fe content of 200ppm (FIG. 5).

Example 2:

100g of refined sugammadex sodium product is taken, 200g of water is added to be dissolved to be clear, 290g of DMF is added at room temperature under stirring, and the solution turns to be slightly turbid after the addition is finished. The solution was transferred to a separatory funnel and allowed to stand for separation, with a small amount of oil settling to the bottom. Separating out oily matter, transferring supernatant into flask, stirring at room temperature, adding 310g DMF, precipitating white solid, vacuum filtering, oven drying to obtain white solid, i.e. sugammadex sodium 85g, purity 99.78% by HPLC (figure 6), Fe content 7.1ppm by ICP-MS, and other element impurity less than 1ppm (figure 7)

Example 3:

100g of refined sugammadex sodium is taken, 400g of water is added to be dissolved to be clear, 750g of acetonitrile is added at room temperature under stirring, and the solution turns to be slightly turbid after the addition is finished. The solution was transferred to a separatory funnel and allowed to stand for separation, with a small amount of oil settling to the bottom. Separating out oily matter, transferring supernatant into flask, stirring at room temperature, adding 1600g ethanol, separating out white solid, vacuum filtering, oven drying to obtain white solid, i.e. sugammadex sodium 73g, purity 99.78% (figure 8) by HPLC, Fe content 7.0ppm by ICP-MS, and other element impurity less than 1ppm (figure 9)

Example 4:

100g of refined sugammadex sodium product is taken, 300g of water is added to be dissolved to be clear, 610g of ethanol is added at room temperature under stirring, and the solution turns to be slightly turbid after the addition is finished. The solution was transferred to a separatory funnel and allowed to stand for separation, with a small amount of oil settling to the bottom. Separating out oily matter, transferring supernatant into a flask, stirring at room temperature, adding 640g of methanol, separating out white solid, performing suction filtration and drying to obtain 73g of white solid, namely sugammadex sodium, the purity of which is 99.79% by HPLC (figure 10), the content of Fe is 8.2ppm by ICP-MS (inductively coupled plasma-Mass Spectrometry), and the content of other element impurities is less than 1ppm (figure 11).

Example 5:

100g of refined sugammadex sodium product is taken, 300g of water is added to be dissolved to be clear, 490g of 1, 4-dioxane is added under stirring at room temperature, and the solution turns to be slightly turbid after the addition is finished. The solution was transferred to a separatory funnel and allowed to stand for separation, with a small amount of oil settling to the bottom. The oil was separated and the supernatant was transferred to a flask and directly concentrated to dryness under reduced pressure to give 79g of sugammadex sodium product with a purity of 99.78% by HPLC (FIG. 12), an Fe content of 7.4ppm by ICP-MS and less than 1ppm of the remaining elemental impurities (FIG. 13).

Example 6:

100g of refined sugammadex sodium was dissolved in 200g of water to obtain a clear solution, and 290g of DMF/DMSO (M: 1) was added thereto at room temperature with stirring, and the solution became slightly turbid after the addition. The solution was transferred to a separatory funnel and allowed to stand for separation, with a small amount of oil settling to the bottom. Separating out oily matter, transferring supernatant into a flask, adding 310g of DMF/DMSO (M: M is 1:1) at room temperature under stirring, precipitating white solid, performing suction filtration, drying to obtain 81g of white solid, namely sugammadex sodium, the purity of which is 99.76% by HPLC (figure 14), and the content of Fe is 8.5ppm by ICP-MS (inductively coupled plasma-Mass Spectrometry), and the content of other element impurities is less than 1ppm (figure 15).

The following brief mechanism is illustrated for the experimental part in examples 1 to 6 of the invention:

1) the invention relates to a process for treating and removing impurities and pigments of excessive elements of sugammadex sodium in research by an applicant. In the production process, after being treated by a common conventional method, the obtained sugammadex sodium product still possibly contains a large amount of excessive element impurities, for example, a raw material adopted in the embodiments 1 to 6 of the invention, namely a refined sugammadex sodium product, is light yellow solid powder, is measured by ICP-MS, wherein the content of Fe is 113ppm, the content of Ti is 6.3ppm, the content of Cr is 6.4ppm, and the content of Co is 1.1ppm, and forms a brownish red or yellowish brown clear solution after being dissolved in water, and the solution has poor effect no matter the conventional treatment means such as crystallization, activated carbon decoloration, ion exchange adsorption and the like are adopted, the treatment method is complex, and the cost is high.

2) In order to solve the above problems, the applicant has made extensive experiments and utilized the feature that an organic solvent which is insoluble in sugammadex sodium and miscible with water is added to an aqueous solution of sugammadex sodium, and the solubility of sugammadex sodium in a mixed solution system is gradually reduced until the sugammadex sodium is precipitated as the proportion of a poor solvent is increased.

3) The technical route described in the preceding examples is, in brief, the drop-wise addition of a poor solvent. When the poor solvent is dripped to a critical point, sugammadex sodium is separated out. Due to the molecular characteristics of sugammadex sodium, the sugammadex sodium can be coated and separated out together with chelate element impurities, pigments and the like. Of course, a small amount of sugammadex sodium was precipitated at this time, and a large amount of product remained in the mother liquor. And the poor solvent is continuously added into the residual mother liquor, so that the proportion of the poor solvent in the mother liquor is continuously increased, and the sugammadex sodium is continuously separated out.

4) Therefore, in the first step of the first or second scheme, the ratio range of the sugammadex sodium refined product, the water and the poor solvent A is not a specific fixed ratio, and according to the solubility characteristics, the ratio range can be summarized as the following four points:

the solubility of sugammadex sodium in water is better, so that the amount of a poor solvent A required for the solution to become turbid is increased when the amount of water is larger, but if the amount of water is too small, the subsequent oily substance is difficult to delaminate, and the loss of sugammadex sodium is too large, so that the mass ratio of the sugammadex sodium refined product to water in the first step is 1: 0.5-1: 50, preferably 1: 1-1: 10, and more preferably 1: 3-1: 4;

the dosage of the poor solvent A is related to the concentration of the sugammadex sodium aqueous solution, more water for dissolving the sugammadex sodium is initially contained, and the total volume of the water and the poor solvent during precipitation is increased by phase change, so more poor solvent is required to be added dropwise; the dropping proportion of the poor solvent A is also related to the poor solvent A, so that the proportion of the water to the poor solvent A is finally selected to be in the range of 1: 0.1-1: 50, preferably 1: 1-1: 10, more preferably 1: 0.5-1: 1, and the proportion can be determined according to repeated experiments of each solvent;

thirdly, the layering process of the oily matter has a plurality of critical points, the poor solvent A is gradually added when the concentration of the initial sugammadex sodium water solution is high, when the poor solvent A reaches a certain value, the solution becomes turbid, and is layered after standing, and a trace amount of oily matter is separated out, which is the initial critical point; continuously adding the poor solvent A, and continuously separating out oily substances until the oily substances are not increased any more, which is a termination critical point; if the poor solvent A is continuously dripped, a solid appears in the oily matter, which indicates that the sugammadex sodium begins to crystallize at the moment, and the poor solvent A cannot be obtained;

the dosage of the poor solvent A is the actual dosage between the initial critical point and the termination critical point, and the proportion of the poor solvent A is better when the oily substance is separated out, so that the yield can be higher and the aim of separating element impurities can be achieved; based on this conclusion, the amount of the poor solvent a closer to the termination critical point was used in examples 1 to 6 of the present invention, and different solvents had different critical values;

due to the excessive experimental amount of the value-by-value experiment, the invention only provides more preferable examples 1-6 for simple demonstration, but does not represent the best experimental scheme of examples 1-6, and the correspondingly adopted content of the poor solvent A, the water and the poor solvent D is not necessarily the best technical scheme; the invention provides the above embodiments only for proving that the method for removing the element ion impurities is a method for removing the element ion impurities which can be popularized and has low cost by using the so-called 'poor solvent detrusion method' and utilizing the property that the cavity structure of sugammadex sodium has the function of adsorbing the element impurities and the pigments to gather most of the element impurities and the pigments into the demixing oily matter, thereby greatly reducing the content of the overproof element impurities in the sugammadex sodium.

5) Referring to fig. 1-15, according to the component analysis of the sugammadex sodium refined product and the oily product and the sugammadex sodium finished product obtained in examples 1-6, compared with the sugammadex sodium refined product, the content of element impurities in the oily product is increased, the content of element impurities in the sugammadex sodium finished product is greatly reduced, the content is reduced from 100ppm to less than or equal to 10ppm, the color is changed from a light yellow sugammadex sodium refined product to pure white sugammadex sodium finished product solid powder, and the effect is obvious to prove that the scheme of the invention is completely feasible. The scheme of the invention can be repeated for a plurality of times to obtain the product with the lowest element impurities and pigments.

6) And (3) as for the oily matter, the total volume of the oily matter is relatively small, part of the sugammadex sodium is still contained in the oily matter, the oily matter which is gathered for many times can be intensively treated, and then the scheme I or the scheme II disclosed by the invention is continuously adopted, and most of the sugammadex sodium in the oily matter is continuously collected so as to avoid waste. The above description is only a preferred embodiment of the present invention and should not be construed as limiting the present invention, and any modifications, equivalent substitutions, improvements, etc. (such as the method of treating the product as free acid by acid-base adjustment and then treating the product according to the method of the present invention, or the method of removing elemental impurities and pigments from the intermediate, crude product, etc. of the production process of the product and then preparing the target product) based on the present patent shall be included in the protection scope of the present invention.

Claims

1. The application of the purification method in removing element impurities and pigments in refined sugammadex sodium products is characterized by comprising the following steps:

in the first step, the mass ratio of the refined sugammadex sodium product to water is 1: 1-1: 10, and the mass ratio of the water to the poor solvent A is 1: 1-1: 10;

2. The use of a purification method according to claim 1 for removing elemental impurities and pigments from a refined sugammadex product, wherein the poor solvent A is selected from the group consisting of acetone, methanol, ethanol, isopropanol, acetonitrile, 1, 4-dioxane, DMF and DMSO, and mixtures thereof.

3. The application of the purification method in removing element impurities and pigments in the refined sugammadex sodium product according to claim 1, wherein the mass ratio of the refined sugammadex sodium product to water in the first step is 1: 3-1: 4.

4. The application of the purification method in removing element impurities and pigments in refined sugammadex sodium products is characterized by comprising the following steps:

step two: transferring the supernatant C into a flask, stirring at room temperature, adding a certain amount of poor solvent D while stirring, separating out white solid, filtering, and drying to obtain a finished product E of sugammadex sodium with elemental impurities and pigments removed;

in the first step, the mass ratio of the refined sugammadex sodium product to water is 1: 1-1: 10, and the mass ratio of the water to the poor solvent A is 1: 1-1: 10; and in the second step, the mass ratio of the supernatant C to the poor solvent D is 1: 1-1: 10.

5. The use of the purification method according to claim 4 for removing elemental impurities and pigments from a refined sugammadex product, wherein the poor solvent A is one or more selected from acetone, methanol, ethanol, isopropanol, acetonitrile, 1, 4-dioxane, DMF and DMSO, and the poor solvent D is one or more selected from acetone, methanol, ethanol, isopropanol, acetonitrile, 1, 4-dioxane, DMF and DMSO.

6. The application of the purification method in removing element impurities and pigments in the refined sugammadex sodium product according to claim 4, wherein the mass ratio of the refined sugammadex sodium product to water in the first step is 1: 3-1: 4; and in the second step, the mass ratio of the supernatant C to the poor solvent D is 1: 2-1: 4.