CN106749771A - A kind of easypro more glucose sodium preparation method of high-purity - Google Patents
A kind of easypro more glucose sodium preparation method of high-purity Download PDFInfo
- Publication number
- CN106749771A CN106749771A CN201510822650.9A CN201510822650A CN106749771A CN 106749771 A CN106749771 A CN 106749771A CN 201510822650 A CN201510822650 A CN 201510822650A CN 106749771 A CN106749771 A CN 106749771A
- Authority
- CN
- China
- Prior art keywords
- sodium
- gamma
- solvent
- cyclodextrins
- ethanol
- 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.)
- Pending
Links
- 0 C*C(C(CCl)OCC1O)[C@@]1*=CCC[C@](C)O Chemical compound C*C(C(CCl)OCC1O)[C@@]1*=CCC[C@](C)O 0.000 description 2
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
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention discloses a kind of easypro more glucose sodium synthetic method of high-purity, its product purity is more than 98%.The synthetic method is comprised the following steps：(1) the full deoxidation -6- perhalogenos of 6--gamma-cyclodextrin, mercaptopropionic acid and alkaline reagent, reaction obtains the easypro more glucose sodium of crude product in certain reaction temperature and action solvent；(2) crude product for obtaining previous step, further recrystallization purifying obtains easypro more glucose sodium of the purity more than more than 98% in a solvent.The method has synthesis step short, and technique is easy and high security, and product quality is high, the advantages of being produced on a large scale.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a muscle relaxant reversal agents are relaxed the more preparation of glucose sodium and purification process.
Background technology
Easypro more glucose sodium (sugammadex), trade name Bridion (cloth Rui Ting), are the novel muscles of Dutch Ou Jianong biotechnologies company exploitation
Lax medicine reversal agents, are a kind of chemical modification objects of cyclodextrin.The medicine 2008 obtains European Union's approval listing, and its mechanism of action is：Optionally wrap
The cloudy stagnant medicine rocuronium of steroid neuromuscular and Vecuronium Bromide are wrapped up in, 1 is formed:The inactive tight water-soluble compound of 1 ratio, so as to block flesh
The function of dried meat floss relaxation medicine, and without the related side effect of anticholinesterase drug.Clinical study results show that it can immediately reverse adult used
Rocuronium effect, the used rocuronium effect of conventional reverse Children and teenager, are the lax bonding agents of first and unique selectivity, are near
First significant pharmaceutical of field of anesthesiology is in progress in decades.The more glucose sodium that relaxes is a kind of gamma-cyclodextrin derivative of improvement, by 8 glucose molecules
It is connected with α-Isosorbide-5-Nitrae glycosidic bond, a hollow taper drum type is similar to, with interior hydrophobic, outer hydrophilic property.Its whole molecule it is all not right
Formation keeping is constant in process of production to claim carbon.
, it is necessary to eight same functional groups in making each molecule participate in chemical reaction completely during more glucose sodium is relaxed in synthesis, high-purity is caused to be relaxed
Preparing for more glucose sodium is extremely complex, and the substantial amounts of impurity similar to its formation and physic-chemical property, these impurity will be produced to be difficult to identify and remove, make
Product Process and quality control difficulties.In addition, the relax special hollow taper drum type structure of more glucose sodium and stronger water soluble nature, make it in life
The impurity such as parcel inorganic salts and small organic molecule are easy to during product.Therefore, the selection of synthesis technique and purifying process is preparing the more glucose sodium that relaxes
During it is very crucial, determine the easypro more glucose sodium that can obtain high-purity.Up to the present, only a small amount of document report is relaxed more glucose sodium
Synthetic route and purification process.
Zhang Mingqiang of Ou Jianong companies et al. (J.Med.Chem.2002,45,1806-1816.) discloses the preparation method of the more glucose sodium that relaxes：By 6-
Full deoxidation -6- perbromo-s-gamma-cyclodextrin, 3- mercapto-propionates and cesium carbonate react in a heated condition, then obtain thick by sodium hydroxide hydrolysis methyl esters
Product, the reaction solution is directly dialysed 6 hours by bag filter and obtains the sterling aqueous solution, then acquisition target product concentrated under reduced pressure.The method reaction time is long,
Relatively costly using cesium carbonate costly, we test discovery product purity highest only 94%.Using saturating in the more purge process of glucose sodium of relaxing
Analysis technology, dialysis time is more long, and dialysis scale is smaller, is suitable only for laboratory and uses, therefore the problem of industrial applications is faced using the purifying process.
Patent CN1188428 discloses another synthetic method of the more glucose sodium that relaxes, by the full deoxidation -6- periodos-gamma-cyclodextrins of 6- and 3- mercaptopropionic acids
Disodium salt heating response, then obtain product through ethanol precipitation and dialysis purification, find product purity only 92% or so through experiment.With the above method one
Sample, the purifying of easypro more glucose sodium is carried out using dialysis process, and purge process is more long, and efficiency is low, and is not suitable for industrial applications.
Document (Chem.Asian is J.2011,6,2390-2399) report selectivity in the presence of triphenylphosphine and iodine using the gamma-cyclodextrin of commercialization
Iodo primary hydroxyl, remaining all secondary hydroxyl acetylations are purified with facilitating by column chromatography, and again with methanol sodium deprotects so as to obtain 6- acetyl group
Full deoxidation -6- periodos-gamma-cyclodextrin, finally in the presence of organic bases triethylamine and 3- mercaptopropionic acids heating response 3 days, then obtains sterling through ultrafiltration.
The synthetic method of the method is cumbersome, and the intermediate full deoxidation -6- periodos-gamma-cyclodextrins of 6- are purified using column chromatography, faces industrial applications problem,
And the final step reaction time is considerably long, consume energy higher.
Patent WO2014125501 reports a kind of preparation method of the full deoxidation -6- perchloro-s-gamma-cyclodextrins of key intermediate 6-, and using in this
Mesosome prepares relax more glucose sodium and purification process in the presence of sodium methoxide with the reaction of 3- mercaptopropionic acids, and its product purity is up to more than 99%.But we pass through
Experiment finds that product purity only has 60% or so, is differed greatly with its literature values, and sodium methoxide easy achievement in 3- mercaptopropionic acid courses of reaction
Freeze shape, it is necessary to substantial amounts of solvent.
In sum, due to the design feature of the more glucose sodium itself that relaxes, the substantial amounts of impurity close with its physicochemical property is produced in building-up process, this
A little impurity such as chromatograph by general purification means, dialyse, crystallize method is difficult to prepare high-quality easypro more glucose sodium.In addition, announce at present
More glucose sodium synthetic method of relaxing is mostly in the presence of inflammable and explosive alkaline reagent sodium hydride, by the full deoxidation -6- perhalogenos-gamma-cyclodextrins of 6- and sulfydryl
Propionic acid reaction is completed, and there is serious safety problem in commercial Application.Therefore, develop new easypro more glucose sodium preparation technology and obtain high-quality
Product is imperative.
The content of the invention
The purpose of the present invention is intended to the problem for overcoming prior art to exist, there is provided a kind of easy to operate, low cost, large-scale production high-purity Shu Geng Portugals
The method of sugared sodium.
Specifically, the preparation method of the easypro more glucose sodium the invention provides one kind as shown in formula (I), and realized using Crystallization Separation technology high
Rapid, the large-scale production technology of quality product.
The technical solution that the present invention is provided is comprised the following steps：
A) mercaptopropionic acid and alkaline reagent react the corresponding salt of acquisition in certain solvent；
B) the full deoxidation -6- perhalogenos-gamma-cyclodextrins of 6- are added in a) salt of the mercaptopropionic acid of step, heating response is complete；
C) reaction solution is concentrated into small size, organic solvent is added to it, the more glucose sodium crude product that must relax is filtered in stirring；
D) crude product is dissolved in a certain amount of distilled water, organic solvent is added dropwise at a certain temperature separates out product, filters to obtain highly finished product.
The easypro more glucose sodium preparation method that the present invention is announced, step a) is characterised by that described alkaline reagent is sodium tert-butoxide, sodium hydride, hydrogen
Sodium oxide molybdena, sodium carbonate, sodium acid carbonate, sodium methoxide, caustic alcohol；Described action solvent is selected from DMF, N, N- dimethylacetamide
Amine, dimethyl sulfoxide (DMSO), tetrahydrofuran, 1,2- dimethoxy-ethane, toluene, ethyl acetate, isopropyl acetate, butyl acetate, acetone, methyl alcohol,
Ethanol, isopropanol, one kind or mixed solvent in water.
The easypro more glucose sodium preparation method that the present invention is announced, it is characterised in that the full deoxidation -6- perhalogenos-gamma-cyclodextrins of 6- are selected from the full deoxidation -6- periodos of 6-
- gamma-cyclodextrin, the full deoxidation -6- perbromo-s-gamma-cyclodextrins of 6- and the full deoxidation -6- perchloro-s-gamma-cyclodextrins of 6-.
The easypro more glucose sodium preparation method that the present invention is announced, it is characterised in that the full deoxidation -6- perhalogenos-gamma-cyclodextrins of 6- and mercaptopropionic acid and alkaline reagent
Molar ratio be 1:8:8~1:15:30.
The easypro more glucose sodium preparation method that the present invention is announced, it is characterised in that the step a) and range of reaction temperature b) are -30~150 DEG C,
Preferred range is 0~100 DEG C.
The easypro more glucose sodium preparation method that the present invention is announced, it is characterised in that solvent is selected from described in step c)：Tetrahydrofuran, dioxane,
Acetonitrile, ethanol, methyl alcohol, the tert-butyl alcohol, n-butanol, acetone, butanone, ethyl acetate, isopropyl acetate, butyl acetate, dichloromethane, trichlorine
Methane, preferably one or more in toluene, methyl alcohol, ethanol, acetone, one or more in ethyl acetate.
The easypro more glucose sodium preparation method that the present invention is announced, it is characterised in that solvent described in step d) is selected from tetrahydrofuran, dioxane, third
Ketone, methyl alcohol, ethanol, isopropanol, n-butanol, preferably one or more in acetonitrile, methyl alcohol, ethanol, one or more in acetone；It is described
Temperature is 0~100 DEG C, preferably 25~80 DEG C.
The preparation technology of the easypro more glucose sodium of the present invention has advantages below：
1) present invention reduces the amount of impurities and content of its building-up process generation using new easypro more glucose sodium preparation technology, significantly improves and relaxes more
The quality and yield of glucose sodium.
2) three relatively low class solvent such as acetone of toxicity, ethanol, ethyl acetate etc. are used in building-up process as far as possible, green production, pole has been truly realized
The earth reduces the pollution to environment.
3), using conventional method for crystallising, purification efficiency is high, and product purity is high, with significant industry for the purge process of the easypro more glucose sodium of the present invention
Change application value.
Specific embodiment
Embodiment 1
Under ice bath, nitrogen protective condition, NaOH (4.4 grams, 0.11mol) is scattered in 100mL DMFs, delayed
It is slow that 3- mercaptopropionic acids (5.3 grams, 0.05mol) is added dropwise, maintain the temperature at 0-5 DEG C.After completion of dropping, it is warmed to room temperature, continues to react 30 minutes.
0 DEG C is cooled to again, is slowly added dropwise the DMF solution of the full deoxidation -6- periodos-gamma-cyclodextrins (10.9 grams, 5mmol) of 6-,
Completion of dropping is warming up to 80 DEG C of reaction 20h.Reactant is concentrated under reduced pressure into small size, the dispersion of water 20mL, 150mL ethanol, stirring, mistake is added
Filter to obtain 8.3 grams of crude product, yield 76%.
Embodiment 2
Under ice bath, nitrogen protective condition, NaOH (4.4 grams, 110mmol) is scattered in 100mL DMFs, slowly
3- mercaptopropionic acids (5.3 grams, 50mmol) is added dropwise, 0-5 DEG C is maintained the temperature at.After completion of dropping, it is warmed to room temperature, continues to react 30 minutes.Again
It is secondary to be cooled to 0 DEG C, the DMF solution of the full deoxidation -6- perbromo-s-gamma-cyclodextrins (9 grams, 5mmol) of 6- is slowly added dropwise, drip
Finish and be warming up to 80 DEG C of reaction 20h.Reactant is concentrated under reduced pressure into small size, the dispersion of water 20mL, 150mL ethanol is added, stirring is filtered slightly
7.7 grams of product, yield 71%.
Embodiment 3
Under ice bath, nitrogen protective condition, NaOH (4.4 grams, 110mmol) is scattered in 100mL DMFs, delayed
It is slow that 3- mercaptopropionic acids (5.3 grams, 50mmol) is added dropwise, maintain the temperature at 0-5 DEG C.After completion of dropping, it is warmed to room temperature, continues to react 30 minutes.
0 DEG C is cooled to again, the DMF solution of the full deoxidation -6- perbromo-s-gamma-cyclodextrins (7.2 grams, 5mmol) of 6- is slowly added dropwise, and is dripped
Add finish be warming up to 100 DEG C it is anti-24 hours.Reactant is concentrated under reduced pressure into small size, the dispersion of water 20mL, 150mL ethanol is added, stirred,
Filter to obtain 6.7 grams of crude product, yield 62%.
Embodiment 4
Under ice bath, nitrogen protective condition, sodium tert-butoxide (10.6 grams, 110mmol) is scattered in the N that dries of 100mL, N- dimethyl formyls
In amine aqueous solution, 3- mercaptopropionic acids (5.3 grams, 50mmol) are slowly added dropwise, maintain the temperature at 0-5 DEG C.After completion of dropping, it is warmed to room temperature, continues anti-
Answer 30 minutes.0 DEG C is cooled to again, is slowly added dropwise the N of the full deoxidation -6- perbromo-s-gamma-cyclodextrins (9 grams, 5mmol) of 6-, N- dimethyl formyls
Amine aqueous solution, completion of dropping is warming up to 80 DEG C of reaction 20h.Reactant is concentrated under reduced pressure into small size, the dispersion of water 20mL, 150mL ethanol is added,
Stirring, filters to obtain 8.5 grams of crude product, yield 78%.
Embodiment 5
Under ice bath, nitrogen protective condition, DMF is dried by what sodium carbonate (11.7 grams, 110mmol) was scattered in 100mL
In solution, 3- mercaptopropionic acids (5.3 grams, 50mmol) are slowly added dropwise, maintain the temperature at 0-5 DEG C.After completion of dropping, it is warmed to room temperature, continues to react
30 minutes.0 DEG C is cooled to again, is slowly added dropwise the DMF of the full deoxidation -6- perbromo-s-gamma-cyclodextrins (9 grams, 5mmol) of 6-
Solution, completion of dropping is warming up to 80 DEG C of reaction 20h.Reactant is concentrated under reduced pressure into small size, the dispersion of water 20mL, 150mL ethanol is added, stirred
Mix, filter to obtain 9.0 grams of crude product, yield 83%.
Embodiment 6
Under ice bath, nitrogen protective condition, sodium carbonate (11.7 grams, 110mmol) is scattered in 100mL DMAs, delayed
It is slow that 3- mercaptopropionic acids (5.3 grams, 50mmol) is added dropwise, maintain the temperature at 0-5 DEG C.After completion of dropping, it is warmed to room temperature, continues to react 30 minutes.
0 DEG C is cooled to again, the DMA solution of the full deoxidation -6- perbromo-s-gamma-cyclodextrins (9 grams, 5mmol) of 6- is slowly added dropwise, and is added dropwise
Finish and be warming up to 80 DEG C of reaction 20h.Reactant is concentrated under reduced pressure into small size, adds the dispersion of water 20mL, 150mL ethanol, stirring to filter
8.4 grams of crude product, yield 77%.
Embodiment 7
Under ice bath, nitrogen protective condition, sodium carbonate (11.7 grams, 110mmol) is scattered in 100mL methyl alcohol, is slowly added dropwise 3- sulfydryls
Propionic acid (5.3 grams, 50mmol), maintains the temperature at 0-5 DEG C.After completion of dropping, it is warmed to room temperature, continues to react 30 minutes.0 DEG C is cooled to again,
Full deoxidation -6- perbromo-s-the gamma-cyclodextrins (9 grams, 5mmol) of 6- are slowly added to, 80 DEG C of reaction 20h are warming up to.Room temperature is cooled to, water 20mL is added,
Stirring, filters to obtain 6.8 grams of crude product, yield 63%.
Embodiment 8
Under ice bath, nitrogen protective condition, sodium acid carbonate (9.2 grams, 110mmol) is scattered in the N that dries of 100mL, N- dimethyl formyls
In amine aqueous solution, 3- mercaptopropionic acids (5.3 grams, 50mmol) are slowly added dropwise, maintain the temperature at 0-5 DEG C.After completion of dropping, it is warmed to room temperature, continues anti-
Answer 30 minutes.0 DEG C is cooled to again, is slowly added dropwise the N of the full deoxidation -6- perbromo-s-gamma-cyclodextrins (9 grams, 5mmol) of 6-, N- dimethyl formyls
Amine aqueous solution, completion of dropping is warming up to 80 DEG C of reaction 20h.Reactant is concentrated under reduced pressure into small size, the dispersion of water 20mL, 150mL ethanol is added,
Stirring, filters to obtain 7.6 grams of crude product, yield 70%.
Embodiment 9
Under ice bath, nitrogen protective condition, sodium methoxide (5.9 grams, 110mmol) is scattered in 100mL DMFs, slow drop
Plus 3- mercaptopropionic acids (5.3 grams, 50mmol), maintain the temperature at 0-5 DEG C.After completion of dropping, it is warmed to room temperature, continues to react 30 minutes.Again
0 DEG C is cooled to, the DMF solution of the full deoxidation -6- perbromo-s-gamma-cyclodextrins (9 grams, 5mmol) of 6-, completion of dropping is slowly added dropwise
It is warming up to 80 DEG C of reaction 20h.Reactant is concentrated under reduced pressure into small size, adds the dispersion of water 20mL, 150mL ethanol, stirring to filter slightly to produce
7.4 grams of product, yield 68%.
Embodiment 10
Easypro 5 grams of the more glucose sodium crude product of the gained of embodiment 5 is dissolved in distilled water, 40 DEG C are heated to, 5 times of acetone of amount volume are added dropwise, separated out white
Color solid, drips off and continues to stir 2 hours after room temperature, and filtering, drying obtains 4.3 grams of sterling, and it is 99.3% to determine purity through HPLC.1HNMR
(D2O):δ=2.41 (brs, 16H), 2.78 (brs, 16H), 2.91-3.07 (m, 16H), 3.55 (brs, 16H), 3.85-3.96 (m, 16H), 5.10 (s, 8H)13CNMR(D2O):δ=180.7,101.6,83.1,72.8,72.5,71.3,37.7,33.2,29.5.
Embodiment 11
Easypro 5 grams of the more glucose sodium crude product of the gained of embodiment 1 is dissolved in distilled water, 50 DEG C are heated to, 5 times of methyl alcohol of amount volume are added dropwise, separated out white
Color solid, is dripped off and continues to stir 2 hours after room temperature, and 4.5 grams of sterling is dried to obtain in filtering, and it is 98.5% to determine purity through HPLC.
Embodiment 12
Easypro 5 grams of the more glucose sodium crude product of the gained of embodiment 2 is dissolved in distilled water, 50 DEG C are heated to, 5 times of ethanol of amount volume are added dropwise, separated out white
Color solid, is dripped off and continues to stir 2 hours after room temperature, and 3.7 grams of sterling is dried to obtain in filtering, and it is 98.8% to determine purity through HPLC.
Although many aspects of the invention and different embodiments, art technology are described in detail by above-mentioned specific embodiment and embodiment
Personnel are based on above-mentioned teaching, and will be easy to predict the method for the invention, reaction condition can have appropriate change and adjustment, specific to adapt to
Need and actual conditions, and these changes and adjustment are thought within the scope of the invention, i.e., in claim limited range.
Claims (8)
1. a kind of high-purity is relaxed the preparation method of more glucose sodium (I), and its feature comprises the following steps：
A) mercaptopropionic acid and alkaline reagent certain solvent and at a temperature of react；
B) the full deoxidation -6- perhalogenos-gamma-cyclodextrins of 6- are added in a) step reaction solution, heating response is complete；
C) reaction solution is concentrated into small size, water and organic solvent is added to it, the more glucose sodium crude product that must relax is filtered in stirring；
D) crude product is dissolved in a certain amount of distilled water, organic solvent is added dropwise at a certain temperature separates out product, filters to obtain highly finished product.
2. the method described in claim 1, it is characterised in that the full deoxidation -6- perhalogenos-gamma-cyclodextrins of 6- are selected from step (a)：Full deoxidation -6- periodos-the gamma-cyclodextrins of 6-, the full deoxidation -6- perbromo-s-gamma-cyclodextrins of 6- and the full deoxidation -6- perchloro-s-gamma-cyclodextrins of 6-；Described alkaline reagent is sodium tert-butoxide, sodium hydride, NaOH, sodium carbonate, sodium acid carbonate, sodium methoxide；Full deoxidation -6- perhalogenos-the gamma-cyclodextrins of 6- are 1 with the molar ratio of mercaptopropionic acid and alkaline reagent:8:8~1:15:30；Described action solvent is selected from DMF, DMA, dimethyl sulfoxide (DMSO), tetrahydrofuran, toluene, ethyl acetate, isopropyl acetate, butyl acetate, acetone, methyl alcohol, ethanol, isopropanol, one kind or mixed solvent in water；Described range of reaction temperature is -30~150 DEG C, and preferred range is 0~50 DEG C.
3. the method described in claim 1, it is characterised in that the reaction temperature of step (b) is 20~100 DEG C, preferably 40~80 DEG C.
4. the method described in claim 1, it is characterised in that solvent is selected from described in step (c)：Tetrahydrofuran, dioxane, acetonitrile, ethanol, methyl alcohol, the tert-butyl alcohol, n-butanol, acetone, butanone, ethyl acetate, dichloromethane, chloroform, one or more in toluene.
5. the method described in claim 4, it is characterised in that solvent described in step (c) preferably is selected from methyl alcohol, ethanol, acetone, one or more in tetrahydrofuran.
6. the method described in claim 1, it is characterised in that solvent is selected from described in step (d)：Tetrahydrofuran, dioxane, acetonitrile, ethanol, methyl alcohol, the tert-butyl alcohol, n-butanol, one or more in acetone.
7. the method described in claim 6, it is characterised in that solvent described in step (d) preferably is selected from methyl alcohol, ethanol, acetone, acetonitrile, one or more in tetrahydrofuran.
8. the method described in claim 1, it is characterised in that the temperature described in step (d) is 0~100 DEG C, preferably 25~80 DEG C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510822650.9A CN106749771A (en) | 2015-11-23 | 2015-11-23 | A kind of easypro more glucose sodium preparation method of high-purity |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510822650.9A CN106749771A (en) | 2015-11-23 | 2015-11-23 | A kind of easypro more glucose sodium preparation method of high-purity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN106749771A true CN106749771A (en) | 2017-05-31 |
Family
ID=58963544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510822650.9A Pending CN106749771A (en) | 2015-11-23 | 2015-11-23 | A kind of easypro more glucose sodium preparation method of high-purity |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106749771A (en) |
Cited By (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107325202A (en) * | 2017-07-06 | 2017-11-07 | 淄博千汇生物科技有限公司 | The process for purification of easypro more glucose sodium |
| CN107325204A (en) * | 2017-07-07 | 2017-11-07 | 中国大冢制药有限公司 | A kind of preparation method for the more glucose sodium that relaxes |
| CN107400182A (en) * | 2017-06-26 | 2017-11-28 | 江苏悦兴医药技术有限公司 | Relax more glucose sodium crystal A and its production and use |
| CN107686530A (en) * | 2017-10-16 | 2018-02-13 | 河北坤安药业有限公司 | A kind of synthetic method for the more glucose sodium that relaxes |
| CN108047354A (en) * | 2017-11-07 | 2018-05-18 | 山东达冠医药科技有限公司 | A kind of high-purity is relaxed the more preparation of glucose sodium and its intermediate and purification process |
| CN108779186A (en) * | 2016-03-22 | 2018-11-09 | 费森尤斯卡比依普莎姆有限责任公司 | A kind of improved method for preparing the more glucose that relaxes |
| 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 |
| CN109021148A (en) * | 2017-06-08 | 2018-12-18 | 天津科伦药物研究有限公司 | A method of preparing the more glucose sodium that relaxes |
| CN109053933A (en) * | 2018-08-01 | 2018-12-21 | 合肥博思科创医药科技有限公司 | A kind of preparation method of the unformed more glucose sodium that relaxes |
| CN109517093A (en) * | 2018-12-29 | 2019-03-26 | 博瑞生物医药（苏州）股份有限公司 | A kind of preparation method of the easypro more glucose sodium of high-purity |
| CN109553702A (en) * | 2018-12-29 | 2019-04-02 | 博瑞生物医药（苏州）股份有限公司 | A kind of purification process for the more glucose sodium that relaxes |
| CN109705237A (en) * | 2018-12-29 | 2019-05-03 | 博瑞生物医药（苏州）股份有限公司 | A kind of preparation method for the more glucose sodium that relaxes |
| WO2019102009A1 (en) | 2017-11-27 | 2019-05-31 | Medichem, S.A. | Process for the synthesis of a cyclodextrin derivative |
| CN109824800A (en) * | 2018-12-29 | 2019-05-31 | 鼎元(天津)生物医药科技有限公司 | A kind of preparation method of the easypro more glucose sodium of selectivity flesh pine antagonistic |
| CN109879986A (en) * | 2019-03-13 | 2019-06-14 | 陈文辉 | A method of preparing relax more glucose sodium and its intermediate |
| TWI668236B (en) * | 2018-07-12 | 2019-08-11 | 台灣神隆股份有限公司 | Method for preparing sugammadex sodium |
| WO2019193198A1 (en) * | 2018-04-06 | 2019-10-10 | Synthon B.V. | Purification of sugammadex |
| 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 |
| CN110655594A (en) * | 2018-06-29 | 2020-01-07 | 江苏海悦康医药科技有限公司 | Preparation method of monohydroxy sugammadex sodium |
| CN110818816A (en) * | 2018-08-10 | 2020-02-21 | 乳源东阳光药业有限公司 | Refining and crystallizing method of sugammadex sodium |
| CN111019016A (en) * | 2019-12-27 | 2020-04-17 | 武汉嘉诺康医药技术有限公司 | Synthesis method of sugammadex impurity |
| CN111040050A (en) * | 2019-12-26 | 2020-04-21 | 徐州工业职业技术学院 | Method for purifying sugammadex sodium |
| CN111518229A (en) * | 2020-05-22 | 2020-08-11 | 合肥博思科创医药科技有限公司 | Method for removing element impurities and pigments in refined sugammadex sodium product |
| CN111548435A (en) * | 2020-05-12 | 2020-08-18 | 杭州泽邦科技有限公司 | Separation and purification method of sugammadex |
| WO2020233522A1 (en) * | 2019-05-22 | 2020-11-26 | 合肥博思科创医药科技有限公司 | Method for preparing high-purity sugammadex sodium |
| WO2021008486A1 (en) * | 2019-07-13 | 2021-01-21 | 刘力 | Novel muscle relaxant antagonistic compounds |
| JP2021527141A (en) * | 2018-06-07 | 2021-10-11 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Manufacturing method of Sugamadex |
| EP3474865B1 (en) | 2016-06-23 | 2022-03-02 | Synthon BV | Process for making sugammadex |
| CN114805639A (en) * | 2021-01-29 | 2022-07-29 | 北京澳合药物研究院有限公司 | Preparation method and application of high-purity sugammadex sodium |
| CN115348974A (en) * | 2020-02-28 | 2022-11-15 | 摩迪康公司 | Method for drying sugammadex |
| CN115505051A (en) * | 2018-06-22 | 2022-12-23 | 四川科伦药物研究院有限公司 | Method for refining sugammadex sodium |
-
2015
- 2015-11-23 CN CN201510822650.9A patent/CN106749771A/en active Pending
Cited By (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108779186A (en) * | 2016-03-22 | 2018-11-09 | 费森尤斯卡比依普莎姆有限责任公司 | A kind of improved method for preparing the more glucose that relaxes |
| CN108779186B (en) * | 2016-03-22 | 2021-07-13 | 费森尤斯卡比依普莎姆有限责任公司 | Improved method for preparing sugammadex |
| EP3474865B1 (en) | 2016-06-23 | 2022-03-02 | Synthon BV | Process for making sugammadex |
| 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 |
| CN109021148A (en) * | 2017-06-08 | 2018-12-18 | 天津科伦药物研究有限公司 | A method of preparing the more glucose sodium that relaxes |
| CN109021148B (en) * | 2017-06-08 | 2020-11-10 | 天津科伦药物研究有限公司 | Method for preparing sugammadex sodium |
| CN107400182A (en) * | 2017-06-26 | 2017-11-28 | 江苏悦兴医药技术有限公司 | Relax more glucose sodium crystal A and its production and use |
| CN107325202A (en) * | 2017-07-06 | 2017-11-07 | 淄博千汇生物科技有限公司 | The process for purification of easypro more glucose sodium |
| CN107325202B (en) * | 2017-07-06 | 2019-09-17 | 淄博千汇生物科技有限公司 | The refining methd of easypro more glucose sodium |
| CN107325204A (en) * | 2017-07-07 | 2017-11-07 | 中国大冢制药有限公司 | A kind of preparation method for the more glucose sodium that relaxes |
| CN107325204B (en) * | 2017-07-07 | 2019-09-24 | 中国大冢制药有限公司 | A kind of preparation method for the more glucose sodium that relaxes |
| CN107686530A (en) * | 2017-10-16 | 2018-02-13 | 河北坤安药业有限公司 | A kind of synthetic method for the more glucose sodium that relaxes |
| CN108047354A (en) * | 2017-11-07 | 2018-05-18 | 山东达冠医药科技有限公司 | A kind of high-purity is relaxed the more preparation of glucose sodium and its intermediate and purification process |
| US11104746B2 (en) | 2017-11-27 | 2021-08-31 | Medichem, S.A. | Process for the synthesis of a cyclodextrin derivative |
| JP7460521B2 (en) | 2017-11-27 | 2024-04-02 | メディチェム エセ．ア． | Method for the synthesis of cyclodextrin derivatives |
| JP2021504505A (en) * | 2017-11-27 | 2021-02-15 | メディチェム エセ．ア． | Methods for the synthesis of cyclodextrin derivatives |
| WO2019102009A1 (en) | 2017-11-27 | 2019-05-31 | Medichem, S.A. | Process for the synthesis of a cyclodextrin derivative |
| CN111615522A (en) * | 2017-11-27 | 2020-09-01 | 摩迪康公司 | Process for the synthesis of cyclodextrin derivatives |
| WO2019193198A1 (en) * | 2018-04-06 | 2019-10-10 | Synthon B.V. | Purification of sugammadex |
| US11225565B2 (en) | 2018-04-06 | 2022-01-18 | Synthon B.V. | Purification of sugammadex |
| EP4047047A1 (en) * | 2018-04-06 | 2022-08-24 | Synthon B.V. | Purification of sugammadex |
| JP7461304B2 (en) | 2018-06-07 | 2024-04-03 | メルク・シャープ・アンド・ドーム・エルエルシー | Manufacturing method of Sugammadex |
| JP2021527141A (en) * | 2018-06-07 | 2021-10-11 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Manufacturing method of Sugamadex |
| 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 |
| CN115505051B (en) * | 2018-06-22 | 2023-07-07 | 四川科伦药物研究院有限公司 | Method for refining sodium gluconate |
| CN115505051A (en) * | 2018-06-22 | 2022-12-23 | 四川科伦药物研究院有限公司 | Method for refining sugammadex sodium |
| 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 |
| CN110655594A (en) * | 2018-06-29 | 2020-01-07 | 江苏海悦康医药科技有限公司 | Preparation method of monohydroxy sugammadex sodium |
| TWI668236B (en) * | 2018-07-12 | 2019-08-11 | 台灣神隆股份有限公司 | Method for preparing sugammadex sodium |
| CN109053933B (en) * | 2018-08-01 | 2020-10-23 | 合肥博思科创医药科技有限公司 | Preparation method of amorphous sugammadex sodium |
| CN109053933A (en) * | 2018-08-01 | 2018-12-21 | 合肥博思科创医药科技有限公司 | A kind of preparation method of the unformed more glucose sodium that relaxes |
| CN110818816A (en) * | 2018-08-10 | 2020-02-21 | 乳源东阳光药业有限公司 | Refining and crystallizing method of sugammadex sodium |
| CN109705237A (en) * | 2018-12-29 | 2019-05-03 | 博瑞生物医药（苏州）股份有限公司 | A kind of preparation method for the more glucose sodium that relaxes |
| CN109517093B (en) * | 2018-12-29 | 2021-03-09 | 博瑞生物医药（苏州）股份有限公司 | Preparation method of high-purity sugammadex sodium |
| CN109517093A (en) * | 2018-12-29 | 2019-03-26 | 博瑞生物医药（苏州）股份有限公司 | A kind of preparation method of the easypro more glucose sodium of high-purity |
| CN109553702A (en) * | 2018-12-29 | 2019-04-02 | 博瑞生物医药（苏州）股份有限公司 | A kind of purification process for the more glucose sodium that relaxes |
| CN109824800A (en) * | 2018-12-29 | 2019-05-31 | 鼎元(天津)生物医药科技有限公司 | A kind of preparation method of the easypro more glucose sodium of selectivity flesh pine antagonistic |
| CN109879986A (en) * | 2019-03-13 | 2019-06-14 | 陈文辉 | A method of preparing relax more glucose sodium and its intermediate |
| WO2020233522A1 (en) * | 2019-05-22 | 2020-11-26 | 合肥博思科创医药科技有限公司 | Method for preparing high-purity sugammadex sodium |
| US11306158B1 (en) | 2019-05-22 | 2022-04-19 | Hefei Bosikc Pharmtech Co., Ltd. | Method for preparing high-purity sugammadex sodium |
| WO2021008486A1 (en) * | 2019-07-13 | 2021-01-21 | 刘力 | Novel muscle relaxant antagonistic compounds |
| CN111040050A (en) * | 2019-12-26 | 2020-04-21 | 徐州工业职业技术学院 | Method for purifying sugammadex sodium |
| CN111019016B (en) * | 2019-12-27 | 2022-02-18 | 武汉嘉诺康医药技术有限公司 | Synthesis method of sugammadex impurity |
| CN111019016A (en) * | 2019-12-27 | 2020-04-17 | 武汉嘉诺康医药技术有限公司 | Synthesis method of sugammadex impurity |
| CN115348974A (en) * | 2020-02-28 | 2022-11-15 | 摩迪康公司 | Method for drying sugammadex |
| CN115348974B (en) * | 2020-02-28 | 2024-03-08 | 摩迪康公司 | Method for drying sugammadex |
| CN111548435B (en) * | 2020-05-12 | 2022-03-18 | 杭州泽邦科技有限公司 | Separation and purification method of sugammadex |
| CN111548435A (en) * | 2020-05-12 | 2020-08-18 | 杭州泽邦科技有限公司 | Separation and purification method of sugammadex |
| CN111518229A (en) * | 2020-05-22 | 2020-08-11 | 合肥博思科创医药科技有限公司 | Method for removing element impurities and pigments in refined sugammadex sodium product |
| CN111518229B (en) * | 2020-05-22 | 2021-02-26 | 合肥博思科创医药科技有限公司 | Method for removing element impurities and pigments in refined sugammadex sodium product |
| CN114805639A (en) * | 2021-01-29 | 2022-07-29 | 北京澳合药物研究院有限公司 | Preparation method and application of high-purity 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 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106749771A (en) | A kind of easypro more glucose sodium preparation method of high-purity | |
| CN106146379B (en) | A kind of synthetic method of Oxiracetam | |
| CN108779186A (en) | A kind of improved method for preparing the more glucose that relaxes | |
| CN108623567A (en) | Ao Si replaces the preparation method of Buddhist nun | |
| CN101863948B (en) | High-purity (2 beta, 3 alpha, 5 alpha, 16 beta, 17 beta)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)-androstane-3,17-diol or composition thereof and preparation method thereof | |
| CN102395591B (en) | Method for preparing prasugrel | |
| CN105693802A (en) | Preparation method of 16 beta-methyl steroid | |
| EP2868657A1 (en) | Method for preparing high purity scutellarin aglycone | |
| CN102146113B (en) | Method for synthesizing 16 alpha-hydroxy prednisolone | |
| CN103159620A (en) | Preparation method of 2-hydroxyisophthalic acid | |
| CN114105800B (en) | Preparation method of 2, 3-diaminomethyl benzoate | |
| CN103664940A (en) | Preparation method of moxifloxacin impurity | |
| CN108101911A (en) | A kind of synthesis technology of sitagliptin intermediate | |
| CN101817796A (en) | Method for preparing cefotiam side chain | |
| CN114409566A (en) | Preparation method of ioversol hydrolysate | |
| CN102010345A (en) | Method for preparing D-phenylalanine through dynamic kinetic resolution | |
| CN107382898B (en) | Energetic material based on ANPZ energetic parent structure and synthetic method thereof | |
| CN108070012B (en) | The method of 6 alpha-fluoro tetraene acetates of highly selective preparation | |
| CN109942442A (en) | A kind of preparation method of the dapoxetine hydrochloride in relation to substance I | |
| CN109336936A (en) | A kind of refining methd of Isepamicin | |
| CN104450851B (en) | A kind of preparation method for removing acetyl cefathiamidine | |
| CN115572262B (en) | Isoquinoline derivative and preparation method thereof | |
| CN102212099A (en) | Synthesis method for dehydroepiandrosterone | |
| CN103113441A (en) | Method for preparing capecitabine | |
| CN103030580A (en) | Preparation method of lapatinib intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20170531 |
|
| WD01 | Invention patent application deemed withdrawn after publication |