CN108358982A - A kind of process for separation and purification of arbekacin sulfate free alkali - Google Patents
A kind of process for separation and purification of arbekacin sulfate free alkali Download PDFInfo
- Publication number
- CN108358982A CN108358982A CN201810321106.XA CN201810321106A CN108358982A CN 108358982 A CN108358982 A CN 108358982A CN 201810321106 A CN201810321106 A CN 201810321106A CN 108358982 A CN108358982 A CN 108358982A
- Authority
- CN
- China
- Prior art keywords
- arbekacin
- free alkali
- gains
- added
- parts
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
- C07H15/222—Cyclohexane rings substituted by at least two nitrogen atoms
- C07H15/226—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings
- C07H15/234—Cyclohexane rings substituted by at least two nitrogen atoms with at least two saccharide radicals directly attached to the cyclohexane rings attached to non-adjacent ring carbon atoms of the cyclohexane rings, e.g. kanamycins, tobramycin, nebramycin, gentamicin A2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of process for separation and purification of arbekacin sulfate free alkali, include the following steps：（1）By 3,2 ', 6 ' three N tertbutyloxycarbonyls, 3 ', 4 ' double deoxidation, 3 ', 4 ' double dehydrogenation kanamycin B N, N dimethacrylamide dissolvings, methylfluoracetate is added；（2）1 tertbutyloxycarbonyl, 3 hydroxyl pyrrolidine and ethyl alcohol are mixed；Then step is added（1）In gains；（3）By step（2）Gains and N, N ' dicyclohexylcarbodiimides and the mixing of N HOSu NHSs；（4）Gained reaction solution is filtered, insoluble matter is filtered off, elutriation is added to go out solid；It filters, tetrahydrofuran dissolving is added in white solid；（5）Adjust gains pH to 8 10；（6）Absorption；（7）Water washing；（8）Elution, is concentrated to dryness；（9）Purifying.The process for separation and purification of the arbekacin sulfate free alkali of the present invention is simple for process, and product purity is high, reduces production cost, it is easy to accomplish industrialized production.
Description
Technical field
The present invention relates to field of medicaments, the process for separation and purification of specifically a kind of arbekacin sulfate free alkali.
Background technology
Arbekacin is a kind of drug, has strong antibacterial to live gentamicin, kanamycins and amikacin drug-fast bacteria
Property, it is clinically used for the infection of respiratory tract, the urinary tract etc..It is that curative effect is best in numerous aminoglycoside antibiotics.2005 2
Month, Arbekacin is classified as 21 century particularly important one of antibiotic by the World Health Organization.The synthesis of Arbekacin at present
The amino protecting group selected in method mainly has 3 kinds：The first is 2- formyl mercaptobenzothiazolers, and second is BOC, the third
It is hmds gastral cavity.
Arbekacin sulfate is a kind of dibekacin analog, to Gram-positive and negative bacterium and most of clinics point
The strain of the resistance to gentamicin separated out, including Pseudomonas aeruginosa and serratia marcescens it is effective, to most of Aminoglycoside inactivators
There is high resistance.Yield and its product of the separating-purifying relationship step of arbekacin sulfate free alkali to arbekacin sulfate
Matter.For the separating-purifying of arbekacin sulfate free alkali, there are the disadvantages such as complicated for operation, purity is low at present.Therefore, of the invention
A kind of process for separation and purification of arbekacin sulfate free alkali is provided.
Invention content
The purpose of the present invention is to provide a kind of process for separation and purification of arbekacin sulfate free alkali, to solve the above-mentioned back of the body
The problem of being proposed in scape technology.
To achieve the above object, the present invention provides the following technical solutions：
A kind of process for separation and purification of arbekacin sulfate free alkali, includes the following steps：（1）By 8-15 parts 3,2 ', 6 '-three-
N- tertbutyloxycarbonyls -3 ', 4 '-double deoxidations -3 ', 10-25 parts of N of 4 ' double dehydrogenation-kanamycin Bs, N- dimethacrylamide are molten
Solution is added 7-11 parts of methylfluoracetates, 1-2h is stirred at 25-35 DEG C；（2）By 5-8 parts of 1- tertbutyloxycarbonyl -3- hydroxyl pyrrolidines
It is mixed with the ethyl alcohol of its 1-2 times of weight, is stirred to react 10-20min；Then step is added in gains（1）In gains, stirring
React 20-35min；（3）By step（2）Gains and 5-7 parts of N, N ' dicyclohexylcarbodiimides and 6-11 parts of N- hydroxysuccinimidyls
Acid imide mixes；It is stirred to react 1-2h；（4）Reaction solution obtained by upper step is filtered, insoluble matter is filtered off, water is added, is precipitated a large amount of solid
Body；White solid is filtered to obtain, tetrahydrofuran dissolving is added；Vacuum distillation removes tetrahydrofuran；（5）Using sodium hydroxide solution
Gains pH to 8-10 is walked in adjusting；（6）Then gains are adsorbed in adsorption zone by ion exchange resin column；（7）
Water washing：After absorption, the feed liquid being mixed in resin gap is washed away by water wash zone and takes away impurity as possible；（8）With ladder
Ammonium hydroxide elution is spent, the flow point of collection belt Arbekacin is concentrated to dryness, and obtains white solid Arbekacin free alkali；（9）White is solid
Body Arbekacin free alkali is dissolved with 75% ethanol solution, and the water of white solid Arbekacin 1-3 times of quality of free alkali is added,
And be put into evaporator, pH value is adjusted to 10-12 using lye；Under normal pressure or vacuum state, heating evaporation device keeps evaporation
Temperature is 70-75 DEG C in device, evaporates 20-40min；Then vacuum distillation recycling ethyl alcohol；Using being concentrated to dryness, it is solid to obtain white
Body Arbekacin free alkali.
As a further solution of the present invention：Step（1）By 10 part of 3,2 ', 6 '-three-N- tertbutyloxycarbonyl -3 ', 4 '-is bis-
Deoxidation -3 ', 4 ' double dehydrogenation-kanamycin Bs are dissolved with 15 parts of N,N-DMAAs, 9 parts of methylfluoracetates of addition, 28 DEG C
Lower stirring 1.3h.
As a further solution of the present invention：Step（2）By 6 parts of 1- tertbutyloxycarbonyl -3- hydroxyl pyrrolidines and its 1.3 times
The ethyl alcohol of weight mixes, and is stirred to react 15min；Then step is added in gains（1）In gains, it is stirred to react 25min.
As a further solution of the present invention：Step（3）By step（2）Gains and 6 parts of N, N ' dicyclohexyls carbon two are sub-
Amine and 8 parts of n-hydroxysuccinimide mixing；It is stirred to react 1.6h.
As a further solution of the present invention：Step（5）Step gains pH to 9 is adjusted using sodium hydroxide solution.
As a further solution of the present invention：Step（9）By white solid Arbekacin free alkali with 75% ethanol solution
Dissolving is added the water of white solid Arbekacin 2 times of quality of free alkali, and is put into evaporator, using lye adjust pH value to
11；Under normal pressure or vacuum state, it is 72 DEG C that heating evaporation device, which keeps temperature in evaporator, evaporates 30min；Then it is evaporated under reduced pressure
Recycle ethyl alcohol；Using being concentrated to dryness, white solid Arbekacin free alkali is obtained.
Compared with prior art, the beneficial effects of the invention are as follows：
The process for separation and purification of the arbekacin sulfate free alkali of the present invention is simple for process, and product purity is high, reduces and is produced into
This, it is easy to accomplish industrialized production；And the hazardous compounds such as hydrazine hydrate are not used, environmental pollution is small；It can efficiently make
The Arbekacin free alkali of high-purity is made, there is preferable economic value and social value.
Specific implementation mode
The technical solution of this patent is described in more detail With reference to embodiment.
Embodiment 1
A kind of process for separation and purification of arbekacin sulfate free alkali, includes the following steps：（1）By 8 part of 3,2 ', 6 '-three-N- uncle
Butoxy carbonyl -3 ', 4 '-double deoxidations -3 ', 4 ' double dehydrogenation-kanamycin Bs are dissolved with 10 parts of N,N-DMAAs, are added 7
Part methylfluoracetate stirs 1h at 25 DEG C；（2）By the ethyl alcohol of 5 parts of 1- tertbutyloxycarbonyl -3- hydroxyl pyrrolidines and its 1 times of weight
Mixing, is stirred to react 10min；Then step is added in gains（1）In gains, it is stirred to react 20min；（3）By step（2）
Gains and 5 parts of N, N ' dicyclohexylcarbodiimides and 6 parts of n-hydroxysuccinimide mixing；It is stirred to react 1h；（4）By upper step
Gained reaction solution filters, and filters off insoluble matter, and water is added, a large amount of solids are precipitated；White solid is filtered to obtain, it is molten that tetrahydrofuran is added
Solution；Vacuum distillation removes tetrahydrofuran；（5）Step gains pH to 8 is adjusted using sodium hydroxide solution；（6）Then by gained
Object is adsorbed in adsorption zone by ion exchange resin column；（7）Water washing：After absorption, is washed away and be mingled with by water wash zone
Feed liquid in resin gap simultaneously takes away impurity as possible；（8）It is eluted with gradient ammonium hydroxide, the flow point of collection belt Arbekacin, concentration
To doing, white solid Arbekacin free alkali is obtained；（9）White solid Arbekacin free alkali is dissolved with 75% ethanol solution,
The water of white solid Arbekacin 1 times of quality of free alkali is added, and is put into evaporator, pH value is adjusted to 10 using lye；
Under normal pressure or vacuum state, it is 70 DEG C that heating evaporation device, which keeps temperature in evaporator, evaporates 20min；Then vacuum distillation recycling
Ethyl alcohol；Using being concentrated to dryness, white solid Arbekacin free alkali is obtained.
Embodiment 2
A kind of process for separation and purification of arbekacin sulfate free alkali, includes the following steps：（1）By 15 part of 3,2 ', 6 '-three-N-
Tertbutyloxycarbonyl -3 ', 4 '-double deoxidations -3 ', 4 ' double dehydrogenation-kanamycin Bs are dissolved with 25 parts of N,N-DMAAs, are added
Enter 11 parts of methylfluoracetates, 2h is stirred at 35 DEG C；（2）By 8 parts of 1- tertbutyloxycarbonyl -3- hydroxyl pyrrolidines and its 2 times of weight
Ethyl alcohol mixes, and is stirred to react 20min；Then step is added in gains（1）In gains, it is stirred to react 35min；（3）It will step
Suddenly（2）Gains and 7 parts of N, N ' dicyclohexylcarbodiimides and 11 parts of n-hydroxysuccinimide mixing；It is stirred to react 2h；（4）
Reaction solution obtained by upper step is filtered, insoluble matter is filtered off, water is added, a large amount of solids are precipitated；White solid is filtered to obtain, tetrahydrochysene furan is added
It mutters dissolving；Vacuum distillation removes tetrahydrofuran；（5）Step gains pH to 10 is adjusted using sodium hydroxide solution；（6）Then
Gains are adsorbed in adsorption zone by ion exchange resin column；（7）Water washing：After absorption, washed by water wash zone
It goes the feed liquid being mixed in resin gap and takes away impurity as possible；（8）It is eluted with gradient ammonium hydroxide, the stream of collection belt Arbekacin
Point, it is concentrated to dryness, obtains white solid Arbekacin free alkali；（9）White solid Arbekacin free alkali is molten with 75% ethyl alcohol
Liquid dissolves, and the water of white solid Arbekacin 3 times of quality of free alkali is added, and is put into evaporator, and pH value is adjusted using lye
To 12；Under normal pressure or vacuum state, it is 75 DEG C that heating evaporation device, which keeps temperature in evaporator, evaporates 40min；Then decompression is steamed
Evaporate recycling ethyl alcohol；Using being concentrated to dryness, white solid Arbekacin free alkali is obtained.
Embodiment 3
A kind of process for separation and purification of arbekacin sulfate free alkali, includes the following steps：（1）By 10 part of 3,2 ', 6 '-three-N-
Tertbutyloxycarbonyl -3 ', 4 '-double deoxidations -3 ', 4 ' double dehydrogenation-kanamycin Bs are dissolved with 15 parts of N,N-DMAAs, are added
Enter 9 parts of methylfluoracetates, 1.3h is stirred at 28 DEG C.（2）By 6 parts of 1- tertbutyloxycarbonyl -3- hydroxyl pyrrolidines and its 1.3 times of weight
Ethyl alcohol mixing, be stirred to react 15min；Then step is added in gains（1）In gains, it is stirred to react 25min.（3）It will
Step（2）Gains and 6 parts of N, N ' dicyclohexylcarbodiimides and 8 parts of n-hydroxysuccinimide mixing；It is stirred to react 1.6h.
（4）Reaction solution obtained by upper step is filtered, insoluble matter is filtered off, water is added, a large amount of solids are precipitated；White solid is filtered to obtain, is added four
Hydrogen furans dissolves；Vacuum distillation removes tetrahydrofuran；（5）Step gains pH to 9 is adjusted using sodium hydroxide solution；（6）So
Gains are adsorbed in adsorption zone by ion exchange resin column afterwards；（7）Water washing：After absorption, pass through water wash zone
It washes away the feed liquid being mixed in resin gap and takes away impurity as possible；（8）It is eluted with gradient ammonium hydroxide, the stream of collection belt Arbekacin
Point, it is concentrated to dryness, obtains white solid Arbekacin free alkali；（9）White solid Arbekacin free alkali is molten with 75% ethyl alcohol
Liquid dissolves, and the water of white solid Arbekacin 2 times of quality of free alkali is added, and is put into evaporator, and pH value is adjusted using lye
To 11；Under normal pressure or vacuum state, it is 72 DEG C that heating evaporation device, which keeps temperature in evaporator, evaporates 30min；Then decompression is steamed
Evaporate recycling ethyl alcohol；Using being concentrated to dryness, white solid Arbekacin free alkali is obtained.
Embodiment 4
A kind of process for separation and purification of arbekacin sulfate free alkali, includes the following steps：（1）By 11 part of 3,2 ', 6 '-three-N-
Tertbutyloxycarbonyl -3 ', 4 '-double deoxidations -3 ', 4 ' double dehydrogenation-kanamycin Bs are dissolved with 18 parts of N,N-DMAAs, are added
Enter 101 parts of methylfluoracetates, 1.7h is stirred at 32 DEG C；（2）By 7.5 parts of 1- tertbutyloxycarbonyl -3- hydroxyl pyrrolidines and its 1.2 times
The ethyl alcohol of weight mixes, and is stirred to react 13min；Then step is added in gains（1）In gains, it is stirred to react 30min；
（3）By step（2）Gains and 6.2 parts of N, N ' dicyclohexylcarbodiimides and 10.2 parts of n-hydroxysuccinimide mixing；It stirs
Mix reaction 1.8h；（4）Reaction solution obtained by upper step is filtered, insoluble matter is filtered off, water is added, a large amount of solids are precipitated；Filter white
Tetrahydrofuran dissolving is added in solid；Vacuum distillation removes tetrahydrofuran；（5）It is adjusted using sodium hydroxide solution and walks gains
PH to 9.5；（6）Then gains are adsorbed in adsorption zone by ion exchange resin column；（7）Water washing：By absorption
Afterwards, the feed liquid being mixed in resin gap is washed away by water wash zone and takes away impurity as possible；（8）It is eluted, is collected with gradient ammonium hydroxide
Flow point with Arbekacin, is concentrated to dryness, and obtains white solid Arbekacin free alkali；（9）White solid Arbekacin is dissociated
Alkali is dissolved with 75% ethanol solution, and the water of white solid Arbekacin 2.7 times of quality of free alkali is added, and is put into evaporator,
PH value is adjusted to 10.5 using lye；Under normal pressure or vacuum state, it is 74 DEG C that heating evaporation device, which keeps temperature in evaporator, is steamed
Send out 35min；Then vacuum distillation recycling ethyl alcohol；Using being concentrated to dryness, white solid Arbekacin free alkali is obtained.
The better embodiment of this patent is explained in detail above, but this patent is not limited to above-mentioned embodiment party
Formula, one skilled in the relevant art within the scope of knowledge, can also be under the premise of not departing from this patent objective
Various changes can be made.
Claims (6)
1. a kind of process for separation and purification of arbekacin sulfate free alkali, which is characterized in that include the following steps：（1）By 8-15
3,2 ', 6 '-three-N- tertbutyloxycarbonyls -3 ' of part, 4 '-double deoxidations -3 ', 4 ' double dehydrogenation-kanamycin Bs 10-25 parts of N, N- diformazans
Base acrylamide dissolves, and 7-11 parts of methylfluoracetates are added, 1-2h is stirred at 25-35 DEG C；（2）By 5-8 parts of 1- tertbutyloxycarbonyls-
3- hydroxyl pyrrolidines and the ethyl alcohol of its 1-2 times of weight mix, and are stirred to react 10-20min；Then step is added in gains（1）
In gains, it is stirred to react 20-35min；（3）By step（2）Gains and 5-7 parts of N, N ' dicyclohexylcarbodiimides and 6-11
Part n-hydroxysuccinimide mixing；It is stirred to react 1-2h；（4）Reaction solution obtained by upper step is filtered, insoluble matter is filtered off, is added
A large amount of solids are precipitated in water；White solid is filtered to obtain, tetrahydrofuran dissolving is added；Vacuum distillation removes tetrahydrofuran；（5）Using
Sodium hydroxide solution adjusts and walks gains pH to 8-10；（6）Then gains are passed through into ion exchange resin column in adsorption zone
It is adsorbed；（7）Water washing：After absorption, the feed liquid being mixed in resin gap is washed away by water wash zone and is taken away as possible
Impurity；（8）It is eluted with gradient ammonium hydroxide, the flow point of collection belt Arbekacin is concentrated to dryness, and it is free to obtain white solid Arbekacin
Alkali；（9）White solid Arbekacin free alkali is dissolved with 75% ethanol solution, white solid Arbekacin free alkali is added
The water of 1-3 times of quality, and be put into evaporator, pH value is adjusted to 10-12 using lye；Under normal pressure or vacuum state, heating
It is 70-75 DEG C that evaporator, which keeps temperature in evaporator, evaporates 20-40min；Then vacuum distillation recycling ethyl alcohol；Using concentration
To doing, white solid Arbekacin free alkali is obtained.
2. the process for separation and purification of arbekacin sulfate free alkali according to claim 1, which is characterized in that step（1）
By 10 part of 3,2 ', 6 '-three-N- tertbutyloxycarbonyl -3 ', 4 '-double deoxidations -3 ', 4 ' double dehydrogenation-kanamycin Bs 15 parts of N, N- bis-
Methacryl amine solvent is added 9 parts of methylfluoracetates, 1.3h is stirred at 28 DEG C.
3. the process for separation and purification of arbekacin sulfate free alkali according to claim 1, which is characterized in that step（2）
6 parts of 1- tertbutyloxycarbonyl -3- hydroxyl pyrrolidines and the ethyl alcohol of its 1.3 times of weight are mixed, 15min is stirred to react；Then by institute
It obtains object and step is added（1）In gains, it is stirred to react 25min.
4. the process for separation and purification of arbekacin sulfate free alkali according to claim 1, which is characterized in that step（3）
By step（2）Gains and 6 parts of N, N ' dicyclohexylcarbodiimides and 8 parts of n-hydroxysuccinimide mixing；It is stirred to react
1.6h。
5. the process for separation and purification of arbekacin sulfate free alkali according to claim 1, which is characterized in that step（5）
Step gains pH to 9 is adjusted using sodium hydroxide solution.
6. the process for separation and purification of arbekacin sulfate free alkali according to claim 1, which is characterized in that step（9）
White solid Arbekacin free alkali is dissolved with 75% ethanol solution, white solid Arbekacin 2 times of quality of free alkali are added
Water, and be put into evaporator, lye used to adjust pH value to 11；Under normal pressure or vacuum state, heating evaporation device keeps steaming
It is 72 DEG C to send out temperature in device, evaporates 30min；Then vacuum distillation recycling ethyl alcohol；Using being concentrated to dryness, obtain white solid Ah
Bekaa star free alkali.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810321106.XA CN108358982A (en) | 2018-04-11 | 2018-04-11 | A kind of process for separation and purification of arbekacin sulfate free alkali |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810321106.XA CN108358982A (en) | 2018-04-11 | 2018-04-11 | A kind of process for separation and purification of arbekacin sulfate free alkali |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108358982A true CN108358982A (en) | 2018-08-03 |
Family
ID=63008021
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810321106.XA Pending CN108358982A (en) | 2018-04-11 | 2018-04-11 | A kind of process for separation and purification of arbekacin sulfate free alkali |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108358982A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1057053A (en) * | 1990-06-07 | 1991-12-18 | 国家医药管理局上海医药工业研究院 | The new synthetic method of Amikacin Sulphate |
| WO2007113841A2 (en) * | 2006-04-03 | 2007-10-11 | Technion Research & Development Foundation Ltd. | Novel aminoglycosides and uses thereof in the treatment of genetic disorders |
| CN101575354A (en) * | 2009-05-26 | 2009-11-11 | 北京化工大学 | Method for synthesizing Arbekacin and intermediate dibekacin thereof |
| CN104447908A (en) * | 2013-09-16 | 2015-03-25 | 常州方圆制药有限公司 | Arbekacin synthesis method |
-
2018
- 2018-04-11 CN CN201810321106.XA patent/CN108358982A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1057053A (en) * | 1990-06-07 | 1991-12-18 | 国家医药管理局上海医药工业研究院 | The new synthetic method of Amikacin Sulphate |
| WO2007113841A2 (en) * | 2006-04-03 | 2007-10-11 | Technion Research & Development Foundation Ltd. | Novel aminoglycosides and uses thereof in the treatment of genetic disorders |
| CN101575354A (en) * | 2009-05-26 | 2009-11-11 | 北京化工大学 | Method for synthesizing Arbekacin and intermediate dibekacin thereof |
| CN104447908A (en) * | 2013-09-16 | 2015-03-25 | 常州方圆制药有限公司 | Arbekacin synthesis method |
Non-Patent Citations (2)
| Title |
|---|
| HAYAMITSU ADACHI ET AL.: "Synthesis and Evaluation of Aminoglycosides as Inhibitors for Rev binding to Rev Responsive Element", 《LETTERS IN DRUG DESIGN & DISCOVERY》 * |
| 李兴刚: "阿贝卡星合成工艺研究", 《化工中间体》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115109172A (en) | Impurities of sugammadex sodium and preparation method thereof | |
| CN107141229A (en) | A kind of method that levodopa is extracted from conversion fluid | |
| CN102850411B (en) | Preparation method of D-glucosamine sulfate potassium chloride salt | |
| CN106631852A (en) | Method for extracting L-ornithine hydrochloride from L-ornithine fermentation broth | |
| CN108997154B (en) | Betaine formulations with low sodium chloride content and low hygroscopicity | |
| CN102351933B (en) | Method for preparing hydroxycobalamin salt | |
| CN111808158A (en) | Preparation method of vitamin B12 crude product | |
| CN108059601A (en) | A kind of technique for preparing 3- amino-1-adamantane alcohols | |
| CN102702279A (en) | Method for preparing clindamycin hydrochloride | |
| CN106928288B (en) | A kind of preparation method of dihydrostreptomycin sulfate | |
| CN108358982A (en) | A kind of process for separation and purification of arbekacin sulfate free alkali | |
| CN108409814A (en) | A kind of preparation method of Etimicin Sulfate | |
| CN106749258A (en) | Method for purifying ertapenem sodium | |
| CN101891159A (en) | Preparation method of analytically pure sodium thiosulfate | |
| CN101880291A (en) | Preparation method of cefpirome sulfate sterile powder | |
| CN101914005B (en) | Method for preparing palladium acetate compound | |
| CN103360412A (en) | A kind of synthetic method of S 578 | |
| CN110627927A (en) | Shugeng sodium gluconate refining method for reducing purification loss rate | |
| CN111056941A (en) | Method for preparing high-purity shikimic acid by utilizing ginkgo leaf extract chromatography waste liquid | |
| CN110128467A (en) | A kind of process of purification of glycerol phosphatidyl choline crude product and its obtained glycerolphosphocholine | |
| CN105949253B (en) | A kind of purification process of Clindamycin Hydrochloride | |
| CN101607893B (en) | Method for obtaining pharmaceutical-grade citric acid from food-grade citric acid | |
| CN115784169A (en) | Purification method of sodium sulfide crystal | |
| CN110684028B (en) | Preparation method of 2, 6-diazabicyclo [3,3,0] octane compound | |
| CN102584614A (en) | Preparation method of L-lysine |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180803 |