CN105968099B - A kind of process for purification of De Lasha stars - Google Patents
A kind of process for purification of De Lasha stars Download PDFInfo
- Publication number
- CN105968099B CN105968099B CN201610318394.4A CN201610318394A CN105968099B CN 105968099 B CN105968099 B CN 105968099B CN 201610318394 A CN201610318394 A CN 201610318394A CN 105968099 B CN105968099 B CN 105968099B
- Authority
- CN
- China
- Prior art keywords
- lasha
- purification according
- alkanones
- stars
- water
- 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
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of process for purification of De Lasha stars, including：(a) De Lasha stars are dissolved in C3 C4 alkanones and the in the mixed solvent of water；(b) activated carbon decolorizing is added；(c) it filters, filtrate stirring and crystallizing；(d) it filters, filtration cakes torrefaction is up to high-purity De Lasha stars.This method is reproducible, easy to operate, and product yield, purity are high, are more suitable for industrialized production.
Description
Technical field
The invention belongs to pharmaceutical technology fields, more particularly to a kind of process for purification of De Lasha stars.
Background technology
The chemical name of De Lasha stars (Delafloxacin) is that 1- (two fluoro- 2- pyridyl groups of 6- amino -3,5-) -8- is chloro-
The fluoro- 7- of 6- (3- hydroxyl -1- azepine -1- cyclobutane base) -4- oxo-Isosorbide-5-Nitrae-dihydro -3- quinoline carboxylic acids, the compound have as follows
Structure：
De Lasha stars are a kind of fluorine quinolone compounds for the brand new developed by Japanese Yong Yong pharmaceutical Co. Ltds
(number：WQ-3034), subsequent U.S. Abbott companies obtain its exploitation license (number：ABT-492), now by Rib-X companies into
III clinical trial phase of row.
De Lasha stars are wide spectrum fluoroquinolone antibiotics of new generation, compared with other quinoline ketone antiseptics, to gram sun
Property bacterium is more effective, especially to the drug resistant methicillin-resistant staphylococcus aureus of other methods for quinolones antibacterial agents (MRSA).
De Lasha stars are appointed as having treatment acute bacterial skin and skin structure infection by the first public declaration of U.S. FDA
(ABSSSI) and the qualification medication of the acquired pneumonia day after tomorrow (CABP).
Chinese patent application CN96198104.0, CN200980138280.X, CN201310021838.4,
CN201410068991.7 discloses the preparation method of De Lasha stars, but the purity of product made from existing method and single impurity
Content do not meet medicinal requirements.
Chinese patent application CN201310124425.9 discloses a kind of process for purification of De Lasha stars, although this method
The relatively high product of purity can be obtained, but refined solvent for use is dioxane, n,N-Dimethylformamide, N, N- diformazans
The high boiling two classes solvent such as yl acetamide, N-Methyl pyrrolidone, dimethyl sulfoxide (DMSO) is easy to remain in the product.
De Lasha stars purity and impurity (＜ 0.1%) meet medicinal standard, with meglumine at the bulk pharmaceutical chemicals obtained by salt
Can just there be higher quality.Therefore, a kind of reproducible, easy to operate, product yield high is developed, the moral of industrialized production is suitble to
The process for purification of husky star is drawn to be of great significance.
Invention content
Inventor developed a kind of process for purification of De Lasha stars, this method is reproducible, easy to operate, product yield
With purity height, it is suitble to industrialized production.
The object of the present invention is to provide a kind of process for purification of the De Lasha stars suitable for industrialization.
In embodiments of the invention, the present invention provides a kind of process for purification of De Lasha stars, and this method includes as follows
Step：
(a) De Lasha stars are dissolved in C3-C4 alkanones and the in the mixed solvent of water, solution temperature is 60-80 DEG C；
(b) activated carbon is added in the solution obtained to step (a), is stirred 20-30 minutes at 60-80 DEG C；
(c) mixture after being stirred in filtration step (b) while hot, the cooling of gained filtrate and insulated and stirred crystallization；
(d) mixture after filtration step (c) stirring and crystallizing, gained filter cake are dried in vacuo at 40-60 DEG C, obtain De La
Sha Xing.
In embodiments of the invention, as the De Lasha stars of starting material can according to methods known in the art come
It prepares, such as CN96198104.0.
In a kind of preferred embodiment of the present invention, a kind of process for purification of De Lasha stars provided by the invention, wherein
In step (a), 1 gram of De Lasha stars are dissolved in 25-55ml, and the mixing of the C3-C4 alkanones and water that are preferably dissolved in 35-45ml is molten
In agent.
In a kind of preferred embodiment of the present invention, a kind of process for purification of De Lasha stars provided by the invention, wherein
In step (a), the C3-C4 alkanones are the mixture of acetone or butanone or both.
In a kind of preferred embodiment of the present invention, a kind of process for purification of De Lasha stars provided by the invention, wherein
The volume ratio of the in the mixed solvent C3-C4 alkanones and water of C3-C4 alkanones and water is 2 in the step (a):1-10:1, preferably
4:1-8:1, more excellent is 5:1-7:1.
In a kind of preferred embodiment of the present invention, a kind of process for purification of De Lasha stars provided by the invention, wherein
The dosage of activated carbon is 0.01-0.1g/1g De Lasha stars in the step (b), preferably 0.03-0.08g/1g De Lasha stars,
More excellent is 0.04-0.06g/1g De Lasha stars, and here, the weight of the De Lasha stars is calculated with starting material.
In a kind of preferred embodiment of the present invention, a kind of process for purification of De Lasha stars provided by the invention, wherein
In the step (c) filtrate cooling and insulated and stirred crystallization temperature be -10 to 20 DEG C, preferably -5 to 10 DEG C, it is more excellent be 0 to
5℃。
In a kind of preferred embodiment of the present invention, a kind of process for purification of De Lasha stars provided by the invention, wherein
The time of step (c) the filtrate cooling and insulated and stirred crystallization is 2-24 hours, and preferably 4-12 hours, more excellent was that 6-10 is small
When.
On the other hand, the present invention also provides a kind of preparation methods of De Lasha stars meglumine, including：
(a) De Lasha stars are dissolved in C3-C4 alkanones and the in the mixed solvent of water, solution temperature is 60-80 DEG C；
(b) activated carbon is added in the solution obtained to step (a), is stirred 20-30 minutes at 60-80 DEG C；
(c) mixture after being stirred in filtration step (b) while hot, the cooling of gained filtrate and insulated and stirred crystallization；
(d) mixture after filtration step (c) stirring and crystallizing, gained filter cake are dried in vacuo at 40-60 DEG C, obtain De La
Sha Xing；
(e) the De Lasha stars that step (d) obtains are heated to 45-55 DEG C with meglumine in water, stirred to clarify, mistake
Filter, filtrate are down to room temperature, and off-white powder is precipitated；
(f) it filters, ethyl alcohol washing is dry, obtains De Lasha star meglumines.
Compared with prior art, De Lasha stars made from the above method of the present invention or De Lasha star meglumines have 99% with
On chromatographic purity, it is single it is miscellaneous is less than 0.1%, meet medicinal requirements.
Therefore, the present invention provides a kind of process for purification of De Lasha stars, this method have it is reproducible, easy to operate,
The advantages that product yield and purity are high, suitable industrialized production.
Specific implementation mode
It is further illustrated the present invention below by embodiment.Should correct understanding be：In the embodiment of the present invention
Method is only used for illustrating the present invention and provides, rather than limiting the invention, so, under the premise of the method for the present invention
The scope of protection of present invention is belonged to the simple modifications of the present invention.
Draw Sha Xingshi, the De Lasha stars used that the side of Chinese patent CN96198104.0 may be used in the following Bender for preparing
Prepared by method, and can be used purification process that its chromatographic purity is made to be more than 98%, for use in following purifying and crystallization.
In the present invention, the related substance chemistry purity analysis method of De Lasha stars is as follows：
Related substance HPLC detection methods：
Stationary phase：C18 columns (4.6 × 250mm × 5 μm)
Mobile phase：Phosphate buffer (0.01mol/l dipotassium hydrogen phosphate solutions tune pH=7.0)-acetonitrile (65:35)
Detection wavelength：285nm
Flow velocity：1.0ml/min
Sample size：10μl
It measures：It takes this product appropriate, mobile phase is added to make dissolving and is diluted to the solution in every 1ml containing about 0.5mg, as examination
Product solution.According to high effective liquid chromatography for measuring, 10 μ l injection liquid chromatographs of contrast solution are taken, by area normalization method, record
Chromatogram.
The preparation of 1 De Lasha stars of embodiment
By 10g De Lasha stars in 170ml acetone and 80ml water, stirring extremely dissolving at 60 DEG C.Addition 0.1g activated carbons, 60
It is stirred 20 minutes at DEG C.It filters while hot, filtrate is cooled to -10 DEG C and insulated and stirred crystallization 2h.Filtering, filter cake vacuum at 40 DEG C
It is dry, obtain faint yellow solid 8.5g, yield 85%, chromatographic purity 99.75%, maximum list miscellaneous 0.07%.
The preparation of 2 De Lasha stars of embodiment
By 10g De Lasha stars in 500ml acetone and 50ml water, stirring extremely dissolving at 80 DEG C.Addition 1g activated carbons, 80 DEG C
Lower stirring 30 minutes.It filters while hot, filtrate is cooled to 20 DEG C and insulated and stirred crystallization for 24 hours.Filtering, filter cake vacuum at 60 DEG C
It is dry, obtain faint yellow solid 8.3g, yield 83%, chromatographic purity 99.78%, maximum list miscellaneous 0.08%.
The preparation of 3 De Lasha stars of embodiment
By 10g De Lasha stars in 300ml acetone and 50ml water, stirring extremely dissolving at 70 DEG C.0.05g activated carbons are added,
It is stirred 25 minutes at 70 DEG C.It filters while hot, filtrate is cooled to 0 DEG C and insulated and stirred crystallization 12h.Filtering, filter cake are true at 50 DEG C
Sky is dry, obtains faint yellow solid 8.6g, yield 86%, chromatographic purity 99.84%, maximum list miscellaneous 0.06%.
The preparation of 4 De Lasha stars of embodiment
By 10g De Lasha stars in 300ml butanone and 50ml water, stirring extremely dissolving at 80 DEG C.0.03g activated carbons are added,
It is stirred 30 minutes at 80 DEG C.It filters while hot, filtrate is cooled to 0 DEG C and insulated and stirred crystallization 10h.Filtering, filter cake are true at 50 DEG C
Sky is dry, obtains faint yellow solid 8.7g, yield 87%, chromatographic purity 99.87%, maximum list miscellaneous 0.07%.
The preparation of 5 De Lasha star meglumines of embodiment
The De Lasha stars that 10g is prepared according to embodiment 1 are heated to 50 DEG C with 6.2g meglumines under 45ml water, stirring,
Stirring is filtered after 30 minutes, and filtrate is down to room temperature, persistently stirs 3h, gradually there is off-white powder precipitation.Continue stir 6h after mistake
Filter, ethyl alcohol washing, dry off-white powder 12.6g, yield 87%, chromatographic purity 99.95%, maximum single miscellaneous 0.02%.
The preparation (being not added with activated carbon decolorizing) of 1 De Lasha stars of comparative example
By 10g De Lasha stars in 170ml acetone and 80ml water, stirring extremely dissolving at 60 DEG C.It is cooled to -10 DEG C and keeps the temperature
Stirring and crystallizing 2h.Filtering, filter cake is dried in vacuo at 40 DEG C, obtains yellow solid 8.6g, yield 86%, chromatographic purity 99.60%,
Maximum single miscellaneous 0.15%.
The preparation of 2 De Lasha star meglumines of comparative example
The De Lasha stars that 10g is prepared according to comparative example 1 are heated to 50 DEG C with 6.2g meglumines under 45ml water, stirring,
Stirring is filtered after 30 minutes, and filtrate is down to room temperature, persistently stirs 3h, gradually there is off-white powder precipitation.Continue stir 6h after mistake
Filter, ethyl alcohol washing, dry off-white powder 12.6g, yield 87%, chromatographic purity 99.78%, maximum single miscellaneous 0.09%.
The preparation (preparation method for pressing CN201310124425.9 embodiments 1) of 3 De Lasha stars of comparative example
13g De Lasha stars are added into 39ml n,N-Dimethylformamide, are heated to 100 DEG C of stirring and dissolvings, slowly in batches
Distilled water is added and muddiness occurs to rigid, about 8.5ml, is slowly dropped to room temperature, lets cool crystallization 8 hours altogether, filters, and filter cake is washed with ethyl alcohol
It washs, is spin-dried for obtaining yellow solid 10g, yield 77%, chromatographic purity 99.45%, maximum list miscellaneous 0.19%.
The preparation of 4 De Lasha star meglumines of comparative example
The De Lasha stars that 10g is prepared according to comparative example 3 are heated to 50 DEG C with 6.2g meglumines under 45ml water, stirring,
Stirring is filtered after 30 minutes, and filtrate is down to room temperature, persistently stirs 3h, gradually there is off-white powder precipitation.Continue stir 6h after mistake
Filter, ethyl alcohol washing, dry off-white powder 12g, yield 83%, chromatographic purity 99.70%, maximum single miscellaneous 0.12%.
Sample made from embodiment 1-5 and comparative example 1-4 is subjected to every detection, the results are shown in Table 1.
Table 1：Sample detection result made from embodiment 1-5 and comparative example 1-4
| Sample source | Molar yield (%) | Chromatographic purity (%) | Maximum single miscellaneous (%) | Character |
| Embodiment 1 | 85 | 99.75 | 0.07 | Faint yellow solid |
| Embodiment 2 | 83 | 99.78 | 0.08 | Faint yellow solid |
| Embodiment 3 | 86 | 99.84 | 0.06 | Faint yellow solid |
| Embodiment 4 | 87 | 99.87 | 0.07 | Faint yellow solid |
| Embodiment 5 | 87 | 99.95 | 0.02 | Off-white powder |
| Comparative example 1 | 86 | 99.60 | 0.15 | Yellow solid |
| Comparative example 2 | 87 | 99.78 | 0.09 | Off-white powder |
| Comparative example 3 | 77 | 99.45 | 0.19 | Yellow solid |
| Comparative example 4 | 83 | 99.70 | 0.12 | Off-white powder |
By the data in table 1 it is found that existing by the molar yield of De Lasha star products made from 1-4 of the embodiment of the present invention
Between 83%-87%, it is respectively 86%, 77% to prepare the yield of the De Lasha stars of gained according to comparative example 1,3 methods；By implementation
The equal ＞ 99.7% of chromatographic purity of De Lasha star products made from example 1-4, maximum single miscellaneous ＜ 0.1%, and made from comparative example 1,3
The equal ＜ 99.7% of chromatographic purity of De Lasha star products, maximum single miscellaneous ＞ 0.1%；It is produced by De Lasha stars made from embodiment 1-4
The character of product is faint yellow solid, and the character of De Lasha star products made from comparative example 1,3 is yellow solid.
The above results show according to De Lasha astrologies ratio made from embodiment 1-4 by De Lasha made from comparative example 1,3
There is star higher chromatographic purity and single miscellaneous control, better character to illustrate the mixed solvent knot using C3-C4 alkanones and water
The operational sequences such as brilliant and activated carbon decolorizing can effectively control foreign pigment and related substance, improve product characteristics, improve product
Quality.
It is 87% by the molar yield of De Lasha stars meglumine product made from the embodiment of the present invention 5, and comparative example 2,4 is made
The molar yield of the De Lasha star meglumine products obtained is respectively 87%, 83%；By De Lasha stars meglumine made from embodiment 5
The chromatographic purity of product is 99.95, and miscellaneous maximum list is 0.02%, and De Lasha stars meglumine product made from comparative example 2,4
Chromatographic purity is respectively 99.78%, 99.70%, and maximum single miscellaneous respectively 0.09%, 0.12%；By the embodiment of the present invention 5 with it is right
The character of De Lasha stars meglumine product is off-white powder made from ratio 2,4.
The above results show to compare according to De Lasha stars meglumine made from embodiment 5 is drawn by moral made from comparative example 2,4
Husky star meglumine has higher chromatographic purity and single miscellaneous control, illustrates that De Lasha stars made from the method for the present invention are used to prepare
The quality higher of De Lasha star meglumine bulk pharmaceutical chemicals is more in line with medicinal requirements, therefore De Lasha stars process for purification of the present invention is to reality
The industrialized production for now meeting the De Lasha star meglumine bulk pharmaceutical chemicals of medicinal requirements is of great significance.
Claims (17)
1. a kind of process for purification of De Lasha stars, includes the following steps：
(a) De Lasha stars are dissolved in C3-C4 alkanones and the in the mixed solvent of water, solution temperature is 60-80 DEG C；
(b) activated carbon is added in the solution obtained to step (a), is stirred 20-30 minutes at 60-80 DEG C；
(c) mixture after being stirred in filtration step (b) while hot, the cooling of gained filtrate and insulated and stirred crystallization；
(d) mixture after filtration step (c) crystallization, gained filter cake are dried in vacuo at 40-60 DEG C, obtain De Lasha stars.
2. process for purification according to claim 1, wherein in step (a), 1 gram of De Lasha stars are dissolved in 25-55ml's
The in the mixed solvent of C3-C4 alkanones and water.
3. process for purification according to claim 1, wherein 1 gram of De Lasha stars are dissolved in 35-45ml's in step (a)
The in the mixed solvent of C3-C4 alkanones and water.
4. process for purification according to claim 1, wherein C3-C4 alkanones are acetone and/or butanone.
5. process for purification according to claim 1, wherein the mixing of C3-C4 alkanones and water described in the step (a) is molten
C3-C4 alkanones and the volume ratio of water are 2 in agent:1-10:1.
6. process for purification according to claim 5, wherein the mixing of C3-C4 alkanones and water described in the step (a) is molten
C3-C4 alkanones and the volume ratio of water 4 in agent:1-8:1.
7. process for purification according to claim 6, wherein the mixing of C3-C4 alkanones and water described in the step (a) is molten
C3-C4 alkanones and the volume ratio of water 5 in agent:1-7:1.
8. process for purification according to claim 1, wherein the dosage of activated carbon is 0.01-0.1g/ in the step (b)
1g De Lasha stars.
9. process for purification according to claim 8, wherein the dosage of activated carbon is 0.03-0.08g/ in the step (b)
1g De Lasha stars.
10. process for purification according to claim 9, wherein the dosage of activated carbon is 0.04- in the step (b)
0.06g/1g De Lasha stars.
11. process for purification according to claim 1, wherein filtrate cooling and insulated and stirred crystallization in the step (c)
Temperature is -10 to 20 DEG C.
12. process for purification according to claim 11, wherein filtrate cooling and insulated and stirred crystallization in the step (c)
Temperature be -5 to 10 DEG C.
13. process for purification according to claim 12, wherein filtrate cooling and insulated and stirred crystallization in the step (c)
Temperature be 0 to 5 DEG C.
14. process for purification according to claim 1, wherein step (c) filtrate cooling and insulated and stirred crystallization when
Between be 2-24 hours.
15. process for purification according to claim 14, wherein step (c) filtrate cooling and insulated and stirred crystallization
Time is 4-12 hours.
16. process for purification according to claim 15, wherein step (c) filtrate cooling and insulated and stirred crystallization
Time is 6-10 hours.
17. a kind of preparation method of De Lasha stars meglumine, including：
(a) De Lasha stars are dissolved in C3-C4 alkanones and the in the mixed solvent of water, solution temperature is 60-80 DEG C；
(b) activated carbon is added in the solution obtained to step (a), is stirred 20-30 minutes at 60-80 DEG C；
(c) mixture after being stirred in filtration step (b) while hot, the cooling of gained filtrate and insulated and stirred crystallization；
(d) mixture after filtration step (c) stirring and crystallizing, gained filter cake are dried in vacuo at 40-60 DEG C, obtain De Lasha
Star；
(e) the De Lasha stars that step (d) obtains are heated to 45-55 DEG C with meglumine in water, stirred to clarify, filtered, filter
Liquid is down to room temperature, and off-white powder is precipitated；
(f) it filters, ethyl alcohol washing is dry, obtains De Lasha star meglumines.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610318394.4A CN105968099B (en) | 2016-05-12 | 2016-05-12 | A kind of process for purification of De Lasha stars |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610318394.4A CN105968099B (en) | 2016-05-12 | 2016-05-12 | A kind of process for purification of De Lasha stars |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105968099A CN105968099A (en) | 2016-09-28 |
| CN105968099B true CN105968099B (en) | 2018-09-25 |
Family
ID=56992551
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610318394.4A Active CN105968099B (en) | 2016-05-12 | 2016-05-12 | A kind of process for purification of De Lasha stars |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105968099B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110467600A (en) * | 2018-05-10 | 2019-11-19 | 上海度德医药科技有限公司 | A kind of De Lasha star meglumine salt crystal form L and preparation method thereof |
| CN111718330A (en) * | 2019-03-23 | 2020-09-29 | 南京海润医药有限公司 | Delafloxacin impurity III and product refining method |
| CN111718329A (en) * | 2019-03-23 | 2020-09-29 | 南京海润医药有限公司 | Delafloxacin impurity IV and product refining method |
| CN111718331A (en) * | 2019-03-23 | 2020-09-29 | 南京海润医药有限公司 | Impurity I and II of delafloxacin and product refining method |
| CN113527262B (en) * | 2021-06-22 | 2022-07-15 | 安徽普利药业有限公司 | Refining method of delafloxacin and meglumine salt thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1789392A2 (en) * | 2004-07-30 | 2007-05-30 | Abbott Laboratories | Preparation of pyridonecarboxylic acid antibacterials |
| CN103936717B (en) * | 2013-01-22 | 2016-08-10 | 上海医药工业研究院 | A kind of delafloxacin intermediate and preparation method thereof |
| CN103936718B (en) * | 2013-01-22 | 2016-06-29 | 上海医药工业研究院 | A kind of preparation method of high-purity delafloxacin |
| CN104098548B (en) * | 2013-04-11 | 2017-07-18 | 上海医药工业研究院 | A kind of Delafloxacin process for purification |
| CN105017224A (en) * | 2015-07-10 | 2015-11-04 | 扬子江药业集团有限公司 | Preparation method of Deller floxacin meglumine crystal form |
-
2016
- 2016-05-12 CN CN201610318394.4A patent/CN105968099B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN105968099A (en) | 2016-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105968099B (en) | A kind of process for purification of De Lasha stars | |
| KR101719366B1 (en) | Process for preparing amorphous refaximin and the amorphous refaximin thus obtained | |
| CN105017223B (en) | De Lasha star meglumine crystal formations I and preparation method thereof | |
| CN103755722B (en) | The synthetic method of a kind of Levofloxacin and Ofloxacine USP 23 | |
| CN103275062B (en) | The purification process of a kind of Pomalidomide | |
| CN104098548B (en) | A kind of Delafloxacin process for purification | |
| CN106831723B (en) | Improved refining method of delafloxacin | |
| CN110183519B (en) | Separation and purification method of dalbavancin key intermediate A40926 | |
| CN107337684B (en) | A kind of preparation method of Faropenem sodium | |
| CN113429299A (en) | Method for purifying phenylenediamine | |
| CN107973796A (en) | A kind of preparation method of Tadalafei isomers | |
| US20140228555A1 (en) | Preparation process of erythromycin thiocyanate | |
| CN103880863B (en) | A kind of preparation method of ampicillin | |
| CN114195720B (en) | Purification method of etomidate | |
| CN102382007B (en) | Doxycycline hydrochloride compound and preparation method thereof | |
| CN110467600A (en) | A kind of De Lasha star meglumine salt crystal form L and preparation method thereof | |
| CN107778331B (en) | Purification method of picoplatin | |
| CN110878082B (en) | Gatifloxacin and its synthesis method | |
| CN105001283A (en) | Azithromycin refining method | |
| CN104402815B (en) | Control method of piperaquine phosphate impurity | |
| US20140121369A1 (en) | Method for purifying ceftizoxime sodium | |
| CN102285986B (en) | Industrialized purification method of moxifloxacin | |
| CN104098547A (en) | Refining method for hydroxyfasudil | |
| CN103030650A (en) | Method for preparing cefotiam hexetil and method for preparing cefotiam hexetil dihydrochloride | |
| CN106279281B (en) | The process for purification of oxazolidone antibiotics safe ground azoles amine phosphate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |