CN107892727B - Method for purifying sugammadex sodium - Google Patents
Method for purifying sugammadex sodium Download PDFInfo
- Publication number
- CN107892727B CN107892727B CN201711206136.8A CN201711206136A CN107892727B CN 107892727 B CN107892727 B CN 107892727B CN 201711206136 A CN201711206136 A CN 201711206136A CN 107892727 B CN107892727 B CN 107892727B
- Authority
- CN
- China
- Prior art keywords
- activated carbon
- sugammadex sodium
- sugammadex
- sodium
- crude
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- 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
Abstract
The invention discloses a purification method of a sugammadex sodium crude product, which adopts specific activated carbon for purification and comprises the following steps: pretreatment of activated carbon, dissolution of crude sugammadex sodium and purification of crude sugammadex sodium. The invention dissolves the crude sugammadex sodium in water or a composition of water and a poor solvent of the sugammadex sodium, and adds the pretreated specific type of activated carbon into the solution to finally obtain the high-purity sugammadex sodium. The purity of sugammadex purified by the method is more than 99.50%, and the single impurity is less than 0.1%. The purification method of the invention has simple operation, low cost and good industrialization prospect.
Description
Technical Field
The invention relates to a purification method of muscle relaxation antagonist sugammadex sodium, which comprises the steps of adding pretreated activated carbon with a specific brand and a specific specification, and purifying a crude product by utilizing the pairing effect of the pore size of the specific activated carbon and impurities in the crude product of the sugammadex sodium and the action of corresponding hydrogen bond adsorption force to obtain the high-purity sugammadex sodium.
Background
Sugammadex sodium is a derivative of gamma-cyclodextrin, the molecule of which consists of a lipophilic core and a hydrophilic outer end, and is a selective muscle relaxant antagonist, the formula of which is C72H104Na8O48S8The structure of the compound is as follows:
sugammadex is a modified gamma-cyclodextrin oligosaccharide, takes synthetic cyclodextrin as a matrix, is water-soluble, is in a truncated cone structure consisting of a lipophilic core and a hydrophilic outer end, and can wrap steroid non-depolarizing muscle relaxants (such as vecuronium bromide and rocuronium bromide) through the lipophilic core to form an inactive compact compound in a ratio of 1:1, so that redistribution of the muscle relaxants is hindered, decomposition of the steroid muscle relaxants and nicotinic acetylcholine receptors is accelerated, and neuromuscular blockade at different depths can be antagonized. The complex is distributed primarily in the central compartment (plasma) and extracellular fluid and is excreted in the urine as a prototype. Sugammadex has high water solubility and biocompatibility, and can directly remove the neuromuscular blocking effect of muscle relaxing medicines at the neuromuscular junction. High selectivity and less side effect.
Akzo Nobel owns a patent right on 6-mercaptocyclodextrin derivatives (publication No. CN1402737A), which was incorporated into Xianlingbao-ya, Mlingbao-ya and later developed sumamadex by Ougangong, Netherlands, the department of human health and health, in 2007, and was purchased by Miner Shadong, Mblend, in 2009. The product has been approved in the european union and japan in 2008 and 2010, respectively. Sodium sugammadex injection (trade name: Bridion) is approved by FDA in 2015, 12 months and 15 days for sale.
According to the synthesis method disclosed in compound patent CN1402737A, sugammadex sodium can be synthesized by the following method:
the above process is carried out by DMF, triphenylphosphine and I2Preparing iodomethylene ammonium salt, iodinating hydroxyl at 6-position of D-glucose unit of gamma-cyclodextrin, and thioetherification in the second step to obtain sugammadex sodium, wherein the iodinated substance and the mercapto compound have higher activity and 8 reaction sites, so that the sugammadex sodium reaction solution has more structural analogs, and the purity is difficult to meet the requirement of the grade of the raw material medicine.
At present, the published literature has few reports on the preparation of high-purity sugammadex sodium, and the main methods are purification by using preparative chromatography and recrystallization, optimization of reaction conditions to reduce the generation of impurities, and removal of partial impurities by using activated carbon to obtain a purer sugammadex sodium product. The defects of preparative chromatographic purification are large solvent consumption, high cost and difficult scale-up of batch; the recrystallization purification operation is complicated, the use amount of the solvent is large, and the quality of the obtained product is unstable; the impurity generation is reduced by controlling the reaction process, and the routes of various purification methods are comprehensively adopted, so that the control points are more, the process stability is poor, and the method is difficult to be applied to actual amplification production.
WO2014125501 (akzo nobel corporation)) discloses a method for preparing sugammadex sodium, which adopts a halophosphine reagent to prepare halo-gamma-cyclodextrin, and then reacts with 3-mercaptopropionic acid under the action of alkali metal alkoxide to form thioether so as to obtain crude sugammadex sodium. And dissolving the crude product in a mixture of water and methanol, adsorbing the mixture by using activated carbon, and adding methanol to recrystallize to obtain the sugammadex sodium crystals. The method improves the synthetic route of the original patent, and adopts a synthetic method to control the purity of the sugammadex sodium product. The activated carbon used in the method is not pretreated and is not screened in species.
WO2017084401 discloses a method for preparing sugammadex sodium, which comprises reacting gamma-cyclodextrin with iodine and triphenylphosphine in an organic solvent to obtain an intermediate iodo-gamma-cyclodextrin. Adding a methanol solution of sodium methoxide into the reaction solution, directly adding acetone without reduced pressure distillation, separating out a solid, and filtering to obtain an iodo-gamma-cyclodextrin crude product; recrystallizing the iodo-gamma-cyclodextrin crude product, and reacting with 3-mercaptopropionic acid under an alkaline condition to obtain a sugammadex sodium crude product; and adsorbing the crude product by an adsorbent, and then recrystallizing to obtain a finished sugammadex sodium product. Wherein the adsorbent is one or a combination of activated carbon, silica gel, macroporous resin, alumina, molecular sieve and zeolite. In the method, the adsorbent is not pretreated, and the figure of the obtained product shows that the oxidation impurities are still high.
The sugammadex sodium is used as a macromolecular drug with an eight-membered glucan structure skeleton, and the molecular structure of the sugammadex sodium is a hollow cup-shaped structure with axial symmetry. In the process of preparing the sugammadex sodium bulk drug, the main impurities which are generated and difficult to remove are mono-substituted or di-substituted impurities with various groups substituted on side chains, the symmetry of the sugammadex sodium molecules is destroyed by the substituent groups, the charge distribution is not uniform, and the polarity of the molecules is increased. Other impurities are impurities formed by the degradation of sugammadex sodium molecules, such as the shedding of side chains, impurities introduced by the interchain condensation of the side chains and the like. The molecular charge arrangement of the chitosan derivative is also greatly different from that of the sugammadex sodium molecule. In addition, the impurities and the sodium sugammadex have certain differences in molecular weight and molecular size. The physical differences between the sugammadex sodium molecule and the impurities thereof lay a foundation for finding a specific adsorbent to adsorb and remove the impurities.
The activated carbon is used as a common adsorbent and is widely applied to various links of purification, impurity removal, decoloration, heat source removal and the like in the industries of chemical industry, food, medicine, environmental protection and the like. The adsorption impurity removal effect of the activated carbon mainly depends on the porous structure on the framework of the activated carbon to contain impurities and van der Waals force between the carbon framework and the impurities to combine the impurities. Because of long history and wide use, the manufacturers and models are very complicated. The active carbon of each manufacturer has great difference in the size and distribution of the pore diameter of the skeleton due to the difference in the production process, material source and the like. Therefore, the active carbon which is suitable for the impurity removal process of sugammadex sodium and can obtain a product with higher purity is screened out, and the method is extremely important for realizing the theoretical assumption.
In addition, the activated carbon contains various components which affect the quality of the sugammadex sodium product, such as ash, adsorbed moisture, oxygen and the like, besides the carbon element skeleton, and a proper pretreatment method needs to be found to eliminate the influence of the factors on the product quality.
The aigret (SHIRASAGI) series activated carbon products were produced by OSAKA gas chemical group of japan (OSAKA GAS CHEMICALS co. ltd, developed by the former wutian pharmaceutical environmental chemical company of japan, incorporated into OSAKA gas chemical group of japan in 2014), and a special aigret (TOKUSEI SHIRASAGI) activated carbon and aigret a (shirasagia) activated carbon were a wood activated carbon product, and were prepared with zinc chloride activated carbon at a high temperature. After activation, the product is washed by a special process, so that the product can reach a high-purity active carbon product used in the production of highly purified and refined medicines.
Disclosure of Invention
The invention provides a purification method of a sugammadex sodium crude product, which adopts specific activated carbon for purification, so that the purification cost is low, and the purity of the obtained final product is high.
In order to solve the technical problem, the purification method of sugammadex sodium of the invention comprises the following steps:
1) and pretreating the activated carbon:
taking special Egret (TOKUSII SHIRASAGI) activated carbon or Egret A (SHIRASAGI) activated carbon, and carrying out activation pretreatment on the special Egret under the protection of nitrogen;
2) dissolution of crude sugammadex sodium:
dissolving the crude sugammadex sodium in water or a mixed solvent consisting of water and a poor solvent of the sugammadex sodium, wherein the concentration is 0.1-90%;
3) and (3) purifying the crude sugammadex sodium:
adding the specially-made aigret (TOKUSEI SHIRAGAII) activated carbon or aigret A (SHIRAGAIA) activated carbon pretreated in the step 1) into the crude sugammadex sodium solution in the step 2), stirring and adsorbing, filtering the activated carbon, concentrating or crystallizing the obtained solution, filtering and drying to obtain the pure sugammadex sodium.
The pretreatment process of the activated carbon in the step 1) is further specifically as follows:
adding special Egret (TOKUSEI SHIRAGAGI) activated carbon or Egret A (SHIRAGAIA) activated carbon and purified water with the weight 1-200 times that of the activated carbon into a three-mouth bottle; under stirring, vacuumizing the three-mouth bottle, introducing nitrogen for replacement, and heating the water/activated carbon mixture in the bottle to boiling; after boiling for 0.1-24 hours, stopping heating, and cooling to room temperature; and (4) carrying out pressure filtration by using nitrogen, wherein the obtained filter cake is pretreated active carbon, and filling nitrogen and sealing for later use.
The amount of the purified water used in the pretreatment process of the activated carbon in the step 1) is preferably 1-20 times of the weight of the activated carbon.
The crude sugammadex sodium product in the step 1) is prepared by a method provided by patent WO 0140316.
Further, the poor solvent of sugammadex sodium in step 2) and the solvent used for crystallization in step 3) are preferably one or a combination of methanol, ethanol, isopropanol, DMF, DMSO, acetonitrile and acetone respectively.
Further, in the mixed solvent in the step 2), the volume ratio of water to the poor solvent of sugammadex sodium is 0.1: 1-1: 100, the volume ratio of water to the sulgammadecaose sodium poor solvent is more preferably 1: 1; the concentration of the crude sugammadex sodium solution in the step 2) is preferably 10-20%.
The dosage of the specially-made aigret (TOKUSEI SHIRASAGI) activated carbon or aigret A (SHIRASAGI) activated carbon in the step 3) is preferably 2-8 g/100 ml.
Compared with the prior art, the invention has the following advantages:
the method comprises the steps of dissolving a crude sugammadex sodium product in water or a composition of water and a poor sugammadex sodium solvent, adding pretreated specific activated carbon into a solution, stirring, adsorbing and purifying, separating the activated carbon, adding the poor sugammadex sodium solvent into the obtained solution, and crystallizing to finally obtain the high-purity sugammadex sodium. The purity of sugammadex obtained by purification of the invention is more than 99.50%, and the single impurity is less than 0.1%.
The method for purifying sugammadex sodium is simple and convenient to operate, low in cost and good in industrial prospect.
Drawings
The present invention will be described in further detail with reference to the accompanying drawings and specific embodiments.
FIG. 1 is an HPLC chart of a finished sugammadex product obtained by treatment of a specially prepared Egret (TOKUSEI SHIRASAGI) in water;
figure 2 is an HPLC diagram of a finished sugammadex sodium product obtained by aigrette a (shirasagia) treatment in water/methanol;
FIG. 3 is a HPLC plot of a finished sugammadex product obtained by treatment of a specially prepared Egret (TOKUSEI SHIRASAGI) in water/DMF;
figure 4 is an HPLC diagram of the sugammadex finished product obtained by processing by aigret M;
figure 5 is an HPLC diagram of the sugammadex sodium end product from aigrette P treatment;
figure 6 is an HPLC plot of the finished sugammadex product from aigret CARBORAFIN treatment;
figure 7 is an HPLC plot of the final sugammadex sodium product from aigrei SEISEI treatment;
figure 8 is an HPLC plot of the sugammadex sodium finished product from KL treatment of granulated aigrette;
figure 9 is an HPLC diagram of the sugammadex sodium finished product obtained by processing aigret FAC-10;
FIG. 10 is an HPLC chart of the sugammadex sodium finished product obtained by the treatment of traditional Chinese medicine activated carbon powder (AR);
FIG. 11 is an HPLC chart of the finished sugammadex sodium product obtained by treatment of activated carbon (AR) of Chinese medicine granules;
FIG. 12 is an HPLC chart of the sugammadex sodium finished product obtained by the treatment of Chinese medicine activated carbon powder (special for drug test);
FIG. 13 is an HPLC chart of the finished sugammadex sodium product from Shanghai activated carbon plant model 767 (needle);
FIG. 14 is an HPLC chart of the finished sugammadex sodium product obtained from activated carbon (for injection) treatment in Shanghai activated carbon plant;
FIG. 15 is an HPLC chart of the sugammadex sodium finished product obtained by treating Jiangsu Lizhu powdered activated carbon;
FIG. 16 is an HPLC chart of the finished sugammadex sodium product obtained by treating Jiangsu Lizhu coconut shell with activated carbon;
FIG. 17 is an HPLC plot of a finished sugammadex product obtained from the treatment of an unpretreated tailored Egret (TOKUSEI SHIRASAGI);
figure 18 is an HPLC plot of the finished sugammadex sodium product obtained from untreated aigret a (shirasagi a) treatment.
Detailed Description
The invention is further described below by way of examples, without limiting the scope of the invention in any way.
The crude sugammadex sodium used in the examples below was prepared according to the method provided in the original patent WO0140316(Akzo Nobel).
Example 1: pretreatment of activated carbon
Taking under the protection of nitrogenSpecial aigrette(TOKUSII SHIRASAGI) 5 g of activated carbon and 100ml of purified water are added into a 250ml three-necked flask which is provided with a mechanical stirrer and is connected with a vacuum device. And (3) under stirring, vacuumizing, introducing nitrogen for replacement, keeping the nitrogen atmosphere, and heating the water/activated carbon mixture in the bottle to boiling. After boiling for 0.5 h, the heating is stopped and the temperature is reduced to room temperature. And (4) carrying out pressure filtration by using nitrogen, wherein the obtained filter cake is pretreated active carbon, and filling nitrogen and sealing for later use.
Example 2: pretreatment of activated carbon
Taking under the protection of nitrogenAigretteA (SHIRASAGI) active carbon 5 g and purified water 100ml are added into a three-mouth bottle 250ml, and the three-mouth bottle is provided with a mechanical stirring device and is connected with a vacuum device. And (3) under stirring, vacuumizing, introducing nitrogen for replacement, keeping the nitrogen atmosphere, and heating the water/activated carbon mixture in the bottle to boiling. After boiling for 0.5 h, the heating is stopped and the temperature is reduced to room temperature. And (4) carrying out pressure filtration by using nitrogen, wherein the obtained filter cake is pretreated active carbon, and filling nitrogen and sealing for later use.
Example 3: and (4) purifying the crude sugammadex sodium.
Yisugamao glucoseAdding 10g crude sodium into 250ml three-necked bottle, and dissolving50ml of newly boiled cold waterIn the nitrogen protection, the pretreated material prepared in example 1 is addedSpecial aigrette(TOKUSII SHIRASAGI) 1g of activated carbon was adsorbed by stirring for 2 hours. The activated carbon was filtered off, and the obtained aqueous solution was concentrated to obtain a pure sugammadex sodium product 9.2g with a purity of 100.0% (sugammadex sodium + monohydroxysgammadex sodium) in the HPLC chart shown in FIG. 1.
Example 4: and (4) purifying the crude sugammadex sodium.
Adding 10g crude sugammadex sodium into 250ml three-necked bottle, and dissolvingMixing 20ml of fresh boiling cold water with 30ml of methanol Synthetic solventIn the nitrogen protection, the pretreated material prepared in example 1 is addedAigretteA (SHIRASAGI) 1g of activated carbon was adsorbed by stirring for 2 hours. The activated carbon was filtered off, and 150ml of methanol was added to the resulting solution, whereby a white solid was precipitated. Filtered and dried to obtain the pure sugammadex sodium product with the purity of 100.0 percent (sugammadex sodium + monohydroxysgammadex sodium), and an HPLC chart is shown in figure 2.
Example 5: and (4) purifying the crude sugammadex sodium.
Adding 10g crude sugammadex sodium into 250ml three-necked bottle, and dissolvingMixing 30ml of fresh boiling chilled water with 30ml of DMF Solvent(s)Under the protection of nitrogen, 4g of the pretreated specially-made aigret (TOKUSEI SHIRASAGI) activated carbon prepared in example 1 was added, and the mixture was stirred and adsorbed for 2 hours. The activated carbon was filtered off, and 100ml of DMF was added to the resulting solution to precipitate a white solid. The solution is filtered and dried to obtain the pure sugammadex sodium product with the purity of 100.0 percent (sugammadex sodium + monohydroxysgammadex sodium), and an HPLC chart is shown in figure 3.
Comparative example 1:
before selecting a pre-treated specially-made aigret (TOKUSEI SHIRASAGI) and aigret a (shirasagia) activated carbon to treat the crude product of purified sugammadex sodium, the effect of treating the crude product of sugammadex sodium by adopting the same method in the above embodiment by respectively testing the activated carbons of different manufacturers and different models which can be purchased in the market. According to verification, except for the activated carbon specified by the invention, other types of activated carbon products can not obtain high-purity sugammadex sodium products, more impurity peaks exist before and after the main peak of sugammadex sodium, and the test results of comparative impurity removal are shown in the following table:
comparative example 2:
to compare the impurity removal effects of pre-treated specially-made Egret (TOKUSEI SHIRASAGI) activated carbon and Egret A (SHIRASAGI) activated carbon, we testedUntreatedThe crude sugammadex sodium was treated with the same method as in the above examples.
Adding 10g of crude sugammadex sodium into a 250ml three-necked bottle, dissolving in 50ml of fresh boiling cold water, and adding under the protection of nitrogenWithout pretreatmentThe special Egret (TOKUSEI SHIRASAGI) active carbon is stirred and adsorbed for 2 hours. The activated carbon was filtered off, and the obtained aqueous solution was concentrated to obtain 9.2g of pure sugammadex sodium with a purity of 96.2% (sugammadex sodium + monohydroxysgammadex sodium), whose HPLC chart is shown in FIG. 17.
Adding 10g of crude sugammadex sodium into a 250ml three-necked flask, dissolving in 50ml of fresh boiled cold water, adding untreated aigrette A (SHIRASAGI) active carbon under the protection of nitrogen, stirring and adsorbing for 2 hours. The activated carbon was filtered off, and the obtained aqueous solution was concentrated to obtain a pure sugammadex sodium product 9.2g having a purity of 94.2% (sugammadex sodium + monohydroxysgammadex sodium), whose HPLC chart is shown in FIG. 18.
Proved by verification, the untreated specially-made aigret (TOKUSEI SHIRASAGI) active carbon and aigret A (SHIRASAGI) active carbon can remove impurity peaks after the main peak in retention time, but specific oxidized impurities are increased in the process of purifying the sugammadex sample, and the impurity peaks before the main peak are not removed and increased, so that the requirement of preparing high-purity sugammadex bulk drug cannot be met.
Claims (6)
1. A method for purifying sugammadex sodium is characterized by comprising the following steps of:
1) and pretreating the activated carbon:
taking special Egret (TOKUSEEISHIRASAGI) activated carbon or Egret A (SHIRASAGI) activated carbon, and carrying out activation pretreatment on the special Egret under the protection of nitrogen;
2) dissolution of crude sugammadex sodium:
dissolving the crude sugammadex sodium in water or a mixed solvent consisting of water and a poor solvent of the sugammadex sodium, wherein the concentration is 0.1-90%;
3) and (3) purifying the crude sugammadex sodium:
adding the specially-made aigrette (TOKUSEISHINIRASAGI) activated carbon or aigrette A (SHIRAAGIA) activated carbon pretreated in the step 1) into the crude sugammadex sodium solution in the step 2), stirring and adsorbing, filtering out the activated carbon, concentrating or crystallizing the obtained solution, filtering and drying to obtain a pure sugammadex sodium product;
the pretreatment process of the activated carbon in the step 1) is as follows:
adding special Egret (TOKUSEISHINASAGI) activated carbon or Egret A (SHIRAAGIA) activated carbon and purified water with the weight of 1-200 times that of the activated carbon into a three-mouth bottle; under stirring, vacuumizing the three-mouth bottle, introducing nitrogen for replacement, and heating the water/activated carbon mixture in the bottle to boiling; after boiling for 0.1-24 hours, stopping heating, and cooling to room temperature; and (4) carrying out pressure filtration by using nitrogen, wherein the obtained filter cake is pretreated active carbon, and filling nitrogen and sealing for later use.
2. A process for the purification of sugammadex sodium according to claim 1, wherein: the amount of the purified water in the pretreatment process of the activated carbon in the step 1) is 1-20 times of the weight of the activated carbon.
3. A process for the purification of sugammadex sodium according to claim 1, wherein: the poor solvent of the sugammadex sodium in the step 2) and the solvent used for crystallization in the step 3) are respectively one or a combination of a plurality of methanol, ethanol, isopropanol, DMF, DMSO, acetonitrile and acetone.
4. A process for the purification of sugammadex sodium according to claim 1, wherein: in the mixed solvent in the step 2), the volume ratio of water to the sulgammadeca sodium poor solvent is 1:1 or 1: 1.5.
5. A process for the purification of sugammadex sodium according to claim 1, wherein: the concentration of the crude sugammadex sodium solution in the step 2) is 10-20%.
6. A process for the purification of sugammadex sodium according to claim 1, wherein:
and 3) the dosage of the special Egret (TOKUSEEISHIRASAGI) active carbon or Egret A (SHIRASAGI) active carbon is 2-8 g/100 ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711206136.8A CN107892727B (en) | 2017-11-27 | 2017-11-27 | Method for purifying sugammadex sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711206136.8A CN107892727B (en) | 2017-11-27 | 2017-11-27 | Method for purifying sugammadex sodium |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107892727A CN107892727A (en) | 2018-04-10 |
| CN107892727B true CN107892727B (en) | 2019-12-24 |
Family
ID=61806365
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711206136.8A Active CN107892727B (en) | 2017-11-27 | 2017-11-27 | Method for purifying sugammadex sodium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107892727B (en) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110615860A (en) * | 2018-06-20 | 2019-12-27 | 江苏恒瑞医药股份有限公司 | Method for purifying sugammadex sodium |
| CN115109172A (en) * | 2018-06-22 | 2022-09-27 | 四川科伦药物研究院有限公司 | Impurities of sugammadex sodium and preparation method thereof |
| CN110655594B (en) * | 2018-06-29 | 2021-04-30 | 江苏海悦康医药科技有限公司 | Preparation method of monohydroxy sugammadex sodium |
| US20210292479A1 (en) | 2018-08-02 | 2021-09-23 | Pliva Hrvatska D.O.O. | Solid state forms of sugammadex sodium |
| US20220049023A1 (en) * | 2018-09-27 | 2022-02-17 | Werthenstein Biopharma Gmbh | Novel crystalline forms of sugammadex |
| CN111978435B (en) | 2019-05-22 | 2021-05-25 | 合肥博思科创医药科技有限公司 | Preparation method of high-purity sugammadex sodium |
| CN110105469A (en) * | 2019-06-12 | 2019-08-09 | 常州亚邦制药有限公司 | The easypro more glucose sodium impurity and preparation method thereof of one kind |
| CN112538124B (en) * | 2019-09-20 | 2023-06-02 | 鲁南制药集团股份有限公司 | Shugansu sodium crystal form |
| CN112538123B (en) * | 2019-09-20 | 2023-06-02 | 鲁南制药集团股份有限公司 | Shugansu sodium crystal form M |
| CN112574330B (en) * | 2019-09-28 | 2023-06-06 | 鲁南制药集团股份有限公司 | Shugansu sodium crystal form |
| CN110627927B (en) * | 2019-10-10 | 2020-08-25 | 深圳市祥根生物科技有限公司 | Shugeng sodium gluconate refining method for reducing purification loss rate |
| CN111548435B (en) * | 2020-05-12 | 2022-03-18 | 杭州泽邦科技有限公司 | Separation and purification method of sugammadex |
| CN111574642B (en) * | 2020-06-23 | 2021-03-19 | 湖南如虹制药有限公司 | Purification method of sugammadex sodium |
| CN114805639B (en) * | 2021-01-29 | 2024-03-22 | 北京澳合药物研究院有限公司 | Preparation method and application of high-purity sodium sugammadex |
| CN113527544B (en) * | 2021-08-06 | 2022-12-30 | 吉林省博大伟业制药有限公司 | Preparation method of high-purity sugammadex sodium |
| CN114773499B (en) * | 2022-05-09 | 2023-03-14 | 四川制药制剂有限公司 | Shugeng sodium gluconate for injection and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI242015B (en) * | 1999-11-29 | 2005-10-21 | Akzo Nobel Nv | 6-mercapto-cyclodextrin derivatives: reversal agents for drug-induced neuromuscular block |
| WO2014125501A1 (en) * | 2013-02-14 | 2014-08-21 | Neuland Laboratories Limited | An improved process for preparation of sugammadex sodium |
| JP6946275B2 (en) * | 2015-05-29 | 2021-10-06 | ラクシュミ・プラサド・アラパルティＬａｋｓｈｍｉ Ｐｒａｓａｄ ＡＬＡＰＡＲＴＨＩ | Manufacturing method of Sugamadex and its intermediates |
| EP3733717A3 (en) * | 2016-03-22 | 2020-12-30 | Fresenius Kabi iPSUM S.r.l. | An improved process for the preparation of sugammadex |
-
2017
- 2017-11-27 CN CN201711206136.8A patent/CN107892727B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN107892727A (en) | 2018-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107892727B (en) | Method for purifying sugammadex sodium | |
| EP3421503B1 (en) | Sugammadex preparation and purification method | |
| JP4594298B2 (en) | High purity fondaparinux sodium composition | |
| CN115505051A (en) | Method for refining sugammadex sodium | |
| CN106831772B (en) | Synthetic method of avibactam intermediate | |
| PT822989E (en) | PROCESS FOR THE PRODUCTION OF CALCIO D-PANTOTENATE | |
| KR20080048989A (en) | Method for purification of chlorinated sucrose derivatives from reaction mixture by chromatography | |
| US20180305388A1 (en) | Crystal of 6'-sialyllactose sodium salt, and process for producing same | |
| CN104231044B (en) | Process for purifying nosiheptide by passing through column | |
| CN111574642B (en) | Purification method of sugammadex sodium | |
| Matsuo et al. | Stereoselective synthesis of β-glycosyl esters of cis-cinnamic acid and its derivatives using unprotected glycosyl donors | |
| CN102557980B (en) | Method for preparing high-purity capsaicine monomer by crystallization | |
| CN108715875B (en) | Method for synthesizing heparin sulfate oligosaccharide with definite structure by enzyme chemistry method | |
| ITMI20122090A1 (en) | SUMMARY OF AN INHIBITOR OF GLYCOSYNTRANSFERASE | |
| CN103539827B (en) | The method of a kind of synthesis to methoxyl group triphenyl α-S-(1 → 6)-D-glucobiose | |
| Riedel et al. | Synthesis and transglycosylase-inhibiting properties of a disaccharide analogue of moenomycin A lacking substitution at C-4 of unit F | |
| CN110128494A (en) | A kind of refining methd of azacitidine | |
| CN110144019B (en) | Refining and purifying method of sugammadex sodium crude product | |
| KR102595725B1 (en) | Method for preparing atropine | |
| JP2018509466A (en) | Crystal form of AHU377, production method and use thereof | |
| CN111394411A (en) | Process method for preparing α -arbutin by enzyme conversion method | |
| CN111116597A (en) | Preparation method of nalbuphine free alkali | |
| CN110790774A (en) | Preparation method of cefdinir impurity D | |
| WO2018079503A1 (en) | Method for purifying p1,p4-di(uridine 5'-)tetraphosphate | |
| JPH03112998A (en) | Preparation of amikacin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |