CN103319504A - Crystallization method for cefotaxime sodium - Google Patents
Crystallization method for cefotaxime sodium Download PDFInfo
- Publication number
- CN103319504A CN103319504A CN2013102656082A CN201310265608A CN103319504A CN 103319504 A CN103319504 A CN 103319504A CN 2013102656082 A CN2013102656082 A CN 2013102656082A CN 201310265608 A CN201310265608 A CN 201310265608A CN 103319504 A CN103319504 A CN 103319504A
- Authority
- CN
- China
- Prior art keywords
- cefotaxime
- sodium
- crystal
- cefotaxime sodium
- crystallization method
- 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
Abstract
The invention discloses a crystallization method for cefotaxime sodium. According to the method, the cefotaxime sodium is prepared by an organic solvent precipitation method in a water-containing system. The method comprises the following preparation steps: adding cefotaxime acid and a sodium salt into a solvent to perform a salt forming reaction at a certain temperature; decoloring, filtering and washing the salt; merging filtrate; adding the solvent dropwise; growing crystals after adding seed crystals; adding a crystallization solvent dropwise for crystallizing; filtering, washing and drying the crystals in vacuum. The cefotaxime sodium obtained by the method has uniform crystal forms, low specific volume and high fluidity, and is easy to package; the cefotaxime sodium is high in clarity, high in purity, light in solution color, low in impurity content, and high in stability, and is easy to store; the process disclosed by the invention is easy to operate and high in product yield. By utilizing the method, the cefotaxime sodium crystals are prepared in the water-containing system, so that the traditional concept that the quality of the product prepared in the water-containing system is poor is broken.
Description
Technical field
The present invention relates to the crystallization method of compound, be specifically related to the crystallization method of cefotaxime sodium in a kind of Aquo System.
Background technology
Cefotaxime sodium (Cefotaxime sodium) is the semi-synthetic broad-spectrum antibiotics of third generation cephalosporin, and its product is white, off-white color or yellowish white crystallization, odorless or little off-odor arranged.Easily molten in water, slightly soluble in methyl alcohol, ethanol, acetone, insoluble in chloroform, normal hexane, methylene dichloride, diethyl ether and ethyl acetate.Molecular formula: C
16H
16N
5O
7S
2Na, molecular weight: 477.44, molecular structural formula is as follows:
The cefotaxime sodium less stable, all may degrade in its amide side chains, lactam nucleus and three positions of ethanoyl, easily be hydrolyzed under the condition that has water molecules to exist, and alkali, acid and temperature raise all can promote its hydrolysis.
The cefotaxime sodium crystallization method adopts the anhydrous system crystallization process usually.Disclose a kind of method for preparing the cefotaxime sodium crystal in the anhydrous solution system such as CN102584854A, it is the solvent system that the method adopts methane amide, ethanamide, dimethyl sulfoxide (DMSO) or methyl alcohol.The method is easy and simple to handle, with short production cycle, but prepared product Determination of Residual Organic Solvents is higher, and solvent recycling difficulty is larger, and the clarity of product solution is relatively poor.WO2011042776A1 discloses a kind of glyme, methyl cellosolve chosen as the crystallization method of solvent system, the crystal mass that the method is prepared is better, but product is mobile relatively poor, the selected solvent price of the method is more expensive, and the loss of solvent causes its high expensive in the production process.For overcoming the existing problem of anhydrous system crystallization method, CN101486719A discloses a kind of aqueous acetone solution of selecting as the crystallization method of solvent system, the method is simple, overcome the unmanageable difficult problem of crystallisation process, but uses the less stable of the prepared product of the method.
Summary of the invention:
The crystallization method that the purpose of this invention is to provide a kind of cefotaxime sodium is to obtaining the cefotaxime sodium crystal of economic environmental protection, good stability.
The objective of the invention is to be realized by following steps:
A) under-10～25 ℃, cefotaxime acid and salt forming agent joined carry out salt-forming reaction in the aqueous vehicle system; Wherein said aqueous vehicle system is by at least a composition the in water and methyl alcohol, ethanol, Virahol, the propyl carbinol;
B) after the stirring clarification, add gac and decolour, filter, with washing lotion screening is carried out washing and filtering, merging filtrate;
C) under-10～25 ℃, in filtrate, drip the crystal precipitation agent, add crystal seed, growing the grain 20～320min again drips the crystal precipitation agent and carries out crystallization; Filter, use the crystal washings that the crystal that filtration obtains is washed, vacuum-drying obtains the cefotaxime sodium crystal.
In order further to embody the beneficial effect that the inventive method possesses, the further preferred following methods of the present invention:
Salt forming agent described in the step a) is one or more in Sodium isooctanoate, sodium bicarbonate, Sodium.alpha.-hydroxypropionate, sodium acetate, sodium methylate, the sodium sulfocynanate; The mol ratio of cefotaxime acid and salt forming agent is 1:1.0～1.5.
The described washing lotion of step b) is one or more in water, methyl alcohol, ethanol, Virahol, propyl carbinol, ethyl acetate, butylacetate, the toluene.
The described crystal precipitation agent of step c) is one or more in methyl alcohol, ethanol, Virahol, propyl carbinol, acetone, ethyl acetate, butylacetate, the toluene; The first addition of crystal precipitation agent is 0.5～10 times of cefotaxime acid quality; The add-on of crystal seed is 0.5 ‰ of cefotaxime acid quality～20 ‰.
In the step c) crystal precipitation agent again addition be 10～45 times of cefotaxime acid quality.
The mass volume ratio of described cefotaxime sodium and aqueous vehicle system is 1:15～60; Described aqueous vehicle system, wherein water accounts for 0.1%～10% of whole system volume.
The crystallization method of described cefotaxime sodium is characterized in that: the described crystal washings of step d) is one or more in water, methyl alcohol, ethanol, Virahol, propyl carbinol, acetone, ethyl acetate, butylacetate, the toluene.
The described vacuum-drying temperature of step d) is 30～55 ℃, and vacuum tightness is 0.09～0.099MPa.
The cefotaxime sodium crystal that the inventive method is prepared, its solution colour is shallow, uniform crystal particles, purity is high, foreign matter content is low, good stability, and the clarity of product, specific volume, flowability and packing more are better than the anhydrous crystal handicraft product.The inventive method has also solved Aquo System simultaneously and has prepared the poor problem of cefotaxime sodium crystal stability.
Embodiment
The below further specifies essentiality content of the present invention with embodiments of the invention, but content of the present invention is not limited to this.
Embodiment 1
Get cefotaxime acid 20g, sodium bicarbonate 4.43g, join in the solvent system that 150ml contains water (this solvent system that contains water is comprised of 15ml water, 135ml methyl alcohol), temperature control-10 ℃ stirs molten clear.Add gac 0.2g, decolouring 30min filters; The charcoal layer that leaches is washed merging filtrate, washings with methyl alcohol.Drip 100ml acetone (crystal precipitation agent) in the temperature control-10 ℃, 60min, add crystal seed 0.3g, growing the grain 60min; In the 100min, drip acetone (crystal precipitation agent) 600ml, carry out crystallization; Filter, with acetone the crystal that filtration obtains is washed; At 40 ℃, be dried to moisture, residual fused lattice under the vacuum tightness 0.093MPa condition.
Its yield: 95.0%; Content: 96.7%; Single largest impurity: 0.3%; Impurity summation: 1.2%; Solution colour: 2+; Clarity 0.25-.
Embodiment 2
Get cefotaxime acid 20g, sodium acetate 4.32g, join in the solvent system that 100ml contains water (this solvent system that contains water is comprised of 20ml water, 80ml ethanol), 0 ℃ of temperature control stirs molten clear.Add gac 0.2g, decolouring 30min filters; The charcoal layer that leaches is washed merging filtrate, washings with ethanol.0 ℃ of temperature control in the 100min, drips butylacetate 80ml, adds crystal seed 0.25g, growing the grain 50min; In the 250min, drip acetone and butylacetate (v/v=1/1) 600ml, filter, with acetone the crystal that filtration obtains is washed; At 35 ℃, be dried to moisture, residual fused lattice under the vacuum tightness 0.095MPa condition.
Its yield: 95.6%, content: 96.2%, single largest impurity: 0.3% impurity summation: 1.3%, solution colour: 2+, clarity 0.25-.
Embodiment 3
Get cefotaxime acid 20g, Sodium isooctanoate 8.76g, join in the solvent system that 120ml contains water (this solvent system that contains water is comprised of 10ml water, 110ml Virahol), 5 ℃ of temperature controls stir molten clear.Add gac 0.2g, decolouring 30min filters; Water, Virahol mixed solution wash merging filtrate, washings to the charcoal layer that leaches.5 ℃ of temperature controls in the 200min, drip Virahol 90ml, add crystal seed 0.4g, growing the grain 40min; In the 300min, drip butylacetate 200ml, filter, with butylacetate the crystal that filtration obtains is washed; At 38 ℃, be dried to moisture, residual fused lattice under the vacuum tightness 0.095MPa condition.
Its yield: 95.1%, content: 96.7%, single largest impurity: 0.3% impurity summation: 1.1%, solution colour: 2+, clarity 0.25-.
Embodiment 4
Get cefotaxime acid 20g, sodium bicarbonate 3.7g, join in the butanol solution of the moisture 5ml of 150ml, 10 ℃ of temperature controls stir molten clear.Add gac 0.2g decolouring 30min, 3ml water and 5ml propyl carbinol are washed the charcoal layer, essence filter, merging filtrate.10 ℃ of temperature controls in the 80min, drip toluene 60ml, add crystal seed 0.01g, growing the grain 20min; In the 300min, drip toluene 400ml, filter, with toluene-acetone soln (v/v=1/5) washed twice filter cake, 50 ℃ of temperature controls, vacuum tightness 0.093MPa are dried to moisture, residual fused lattice.
Its yield: 95.7%, content: 96.4%, single largest impurity: 0.3%, the impurity summation: 1.2%, solution colour: 2, clarity 0.25-.
Embodiment 5
Get cefotaxime acid 20g, sodium methylate 2.85g, join in the solution of ethanol that 160ml contains 8ml water, 15 ℃ of temperature controls stir molten clear.Add gac 0.2g decolouring 30min, 10ml ethanol is washed the charcoal layer, essence filter, merging filtrate.15 ℃ of temperature controls in the 90min, drip ethanol 150ml, add crystal seed 0.05g, growing the grain 90min; In the 90min, drip acetone 500ml, filter, with ethyl acetate washed twice filter cake, 45 ℃ of temperature controls, vacuum tightness 0.098MPa are dried to moisture, residual fused lattice.
Its yield: 95.2%, content: 96.3%, single largest impurity: 0.3% impurity summation: 1.1%, solution colour: 2, clarity 0.25-.
Embodiment 6
Get cefotaxime acid 20g, sodium acetate 1.91g, 5.62g 60% Sodium.alpha.-hydroxypropionate joins in the 100ml methanol solution that contains the 40ml Virahol, 20 ℃ of temperature controls stir molten clear.Add gac 0.2g decolouring 30min, 10ml toluene is washed the charcoal layer, essence filter, merging filtrate.20 ℃ of temperature controls in the 70min, drip acetone 100ml, add crystal seed 0.1g, growing the grain 120min; In the 80min, drip acetone 300ml, filter, with twice filter cake of washing with acetone, 40 ℃ of temperature controls, vacuum tightness 0.096MPa are dried to moisture, residual fused lattice.
Yield: 95.5%, content: 96.5%, single largest impurity: 0.3% impurity summation: 1.2%, solution colour: 2, clarity 0.25-.
Embodiment 7 experiment contrasts
By the product of the inventive method preparation and carrying out initial experiment relatively and accelerating experiment relatively by the prior art preparation.Wherein sample A is the embodiment of the invention 2 prepared products, and anhydrous system product 1 prepares according to the described method of following comparison example with anhydrous system product 2.Comparing result is shown in table 1, table 2.
Comparison example 1
(1) salify: when temperature during at 5～8 ℃, 20g cefotaxime acid and 4.15g sodium acetate joined in the anhydrous solution medium (35ml ethanamide, anhydrous methanol 15ml) carry out salt-forming reaction, stir, after the solution clarification, add 0.2g activated carbon decolorizing 30min, filtration, anhydrous methanol washing charcoal layer, merging filtrate;
(2) crystallization: drip the 100ml Virahol in 5～10 ℃ of the temperature controls, 40min in filtrate, add the 0.2g crystal seed, growing the grain 30min continues to drip 350ml ethyl acetate crystallization;
(3) filter, with the cefotaxime sodium crystal that the ethyl acetate washing obtains, 40 ℃ of temperature controls, vacuum tightness 0.098MPa drying obtains anhydrous system product 1.
Comparison example 2
(1) salify: when temperature during at-5～0 ℃, 20g cefotaxime acid, 4.20g Sodium isooctanoate joined in the anhydrous solution medium (15ml methane amide, anhydrous methanol 45ml) carry out salt-forming reaction, after being stirred to the solution clarification, add 0.2g activated carbon decolorizing 30min, filtration, methane amide washing charcoal layer, merging filtrate;
(2) crystallization: drip 100ml acetone in 0～5 ℃ of the temperature control, 40min in filtrate, add the 0.1g crystal seed, growing the grain 60min continues to drip 400ml acetone crystallization;
(3) filter, with the cefotaxime sodium crystal that washing with acetone obtains, 45 ℃ of temperature controls, vacuum tightness 0.099MPa drying obtains anhydrous system product 2.
Table 1 initial experiment Data Comparison
Sample A and anhydrous system product 1,2 accelerate data comparison after three months:
Accelerated test condition: temperature: 40 ℃ ± 2 ℃, relative humidity: 75% ± 5%, the pick-up period: 3 months.
Table 2 accelerates the experimental data contrast
Data from above-mentioned two forms can be found out, the product that uses the described method of invention to make in Aquo System is compared with the anhydrous system product, and its stability is higher, and foreign matter content is low, clarity of solution is more excellent, has broken the traditional concept that makes poor product quality in Aquo System.
Claims (8)
1. the crystallization method of a cefotaxime sodium is characterized in that may further comprise the steps:
A) under-10～25 ℃, cefotaxime acid and salt forming agent joined carry out salt-forming reaction in the aqueous vehicle system; Wherein said aqueous vehicle system is by at least a composition the in water and methyl alcohol, ethanol, Virahol, the propyl carbinol;
B) after the stirring clarification, add gac and decolour, filter, with washing lotion screening is carried out washing and filtering, merging filtrate;
C) under-10～25 ℃, in filtrate, drip the crystal precipitation agent, add crystal seed, growing the grain 20～320min again drips the crystal precipitation agent and carries out crystallization; Filter, use the crystal washings that the crystal that filtration obtains is washed, vacuum-drying obtains the cefotaxime sodium crystal.
2. the crystallization method of cefotaxime sodium according to claim 1, it is characterized in that: salt forming agent described in the step a) is one or more in Sodium isooctanoate, sodium bicarbonate, Sodium.alpha.-hydroxypropionate, sodium acetate, sodium methylate, the sodium sulfocynanate; The mol ratio of cefotaxime acid and salt forming agent is 1:1.0～1.5.
3. the crystallization method of cefotaxime sodium according to claim 1 and 2, it is characterized in that: the described washing lotion of step b) is one or more in water, methyl alcohol, ethanol, Virahol, propyl carbinol, ethyl acetate, butylacetate, the toluene.
4. the crystallization method of cefotaxime sodium according to claim 1 and 2, it is characterized in that: the described crystal precipitation agent of step c) is one or more in methyl alcohol, ethanol, Virahol, propyl carbinol, acetone, ethyl acetate, butylacetate, the toluene; The first addition of crystal precipitation agent is 0.5～10 times of cefotaxime acid quality; The add-on of crystal seed is 0.5 ‰ of cefotaxime acid quality～20 ‰.
5. the crystallization method of cefotaxime sodium according to claim 1 and 2, it is characterized in that crystal precipitation agent in the step c) again addition be 10～45 times of cefotaxime acid quality.
6. the mass volume ratio of cefotaxime sodium according to claim 1 and 2 and aqueous vehicle system is 1:15～60; Described aqueous vehicle system, wherein water accounts for 0.1%～10% of whole system volume.
7. the crystallization method of cefotaxime sodium according to claim 1, it is characterized in that: the described crystal washings of step d) is one or more in water, methyl alcohol, ethanol, Virahol, propyl carbinol, acetone, ethyl acetate, butylacetate, the toluene.
8. the crystallization method of cefotaxime sodium according to claim 1, it is characterized in that: the described vacuum-drying temperature of step d) is 30～55 ℃, and vacuum tightness is 0.09～0.099MPa.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102656082A CN103319504A (en) | 2013-06-28 | 2013-06-28 | Crystallization method for cefotaxime sodium |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2013102656082A CN103319504A (en) | 2013-06-28 | 2013-06-28 | Crystallization method for cefotaxime sodium |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103319504A true CN103319504A (en) | 2013-09-25 |
Family
ID=49188592
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2013102656082A Pending CN103319504A (en) | 2013-06-28 | 2013-06-28 | Crystallization method for cefotaxime sodium |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103319504A (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892636A (en) * | 2015-05-21 | 2015-09-09 | 天津大学 | Method for preparing cefotaxime sodium crystal |
| CN107049958A (en) * | 2017-04-26 | 2017-08-18 | 四川制药制剂有限公司 | The preparation technology of cefotaxime sodium for injection powder-injection |
| CN108096198A (en) * | 2017-12-26 | 2018-06-01 | 金华智济药物科技合伙企业（有限合伙） | Novel antibacterial pharmaceutical composition when prevention and treatment aerobic bacteria and anaerobic bacteria mixed infection and preparation method thereof |
| CN108409753A (en) * | 2018-04-08 | 2018-08-17 | 天津大学 | A kind of preparation method of Cefotaxime Sodium sphaerocrystal |
| CN112442048A (en) * | 2020-11-10 | 2021-03-05 | 华北制药河北华民药业有限责任公司 | Preparation method of cefpiramide sodium |
| CN112480145A (en) * | 2020-12-09 | 2021-03-12 | 山东鲁抗医药股份有限公司 | Preparation method of cefotaxime sodium |
| CN113666947A (en) * | 2021-07-23 | 2021-11-19 | 无锡海伦生物科技有限公司 | Preparation method of cefotaxime sodium |
| US11186605B2 (en) | 2016-10-06 | 2021-11-30 | Kyowa Hakko Bio Co., Ltd. | Crystal of cytidine diphosphate choline and production method thereof |
| CN114028336A (en) * | 2021-10-20 | 2022-02-11 | 华北制药河北华民药业有限责任公司 | Preparation method of cefotaxime sodium for injection |
| RU2800932C2 (en) * | 2016-10-06 | 2023-08-01 | Киова Хакко Био Ко., Лтд. | Cytidine diphosphate choline crystal and method for its production |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996020198A1 (en) * | 1994-12-23 | 1996-07-04 | Biochemie Gesellschaft Mbh | Production of cefotaxime and new sodium salts |
| CN1394863A (en) * | 2002-07-05 | 2003-02-05 | 上海新亚药业有限公司 | Method for synthesizing cefotaxime sodium |
| WO2004063203A1 (en) * | 2003-01-10 | 2004-07-29 | Orchid Chemicals & Pharmaceuticals Ltd | Process for the preparation of cefotaxime sodium |
| CN101486719A (en) * | 2009-02-17 | 2009-07-22 | 福建省福抗药业股份有限公司 | Method for converting cefotaxime acid into sodium salt crystal |
-
2013
- 2013-06-28 CN CN2013102656082A patent/CN103319504A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996020198A1 (en) * | 1994-12-23 | 1996-07-04 | Biochemie Gesellschaft Mbh | Production of cefotaxime and new sodium salts |
| CN1394863A (en) * | 2002-07-05 | 2003-02-05 | 上海新亚药业有限公司 | Method for synthesizing cefotaxime sodium |
| WO2004063203A1 (en) * | 2003-01-10 | 2004-07-29 | Orchid Chemicals & Pharmaceuticals Ltd | Process for the preparation of cefotaxime sodium |
| CN101486719A (en) * | 2009-02-17 | 2009-07-22 | 福建省福抗药业股份有限公司 | Method for converting cefotaxime acid into sodium salt crystal |
Non-Patent Citations (2)
| Title |
|---|
| 胡文滨: "头孢噻肟钠的精制", 《河北化工》, vol. 34, no. 7, 31 July 2011 (2011-07-31), pages 6 - 8 * |
| 赵洪娥，等: "头孢噻肟钠结晶工艺的研究", 《河北化工》, vol. 36, 28 February 2013 (2013-02-28), pages 9 - 16 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104892636A (en) * | 2015-05-21 | 2015-09-09 | 天津大学 | Method for preparing cefotaxime sodium crystal |
| US11186605B2 (en) | 2016-10-06 | 2021-11-30 | Kyowa Hakko Bio Co., Ltd. | Crystal of cytidine diphosphate choline and production method thereof |
| RU2800932C2 (en) * | 2016-10-06 | 2023-08-01 | Киова Хакко Био Ко., Лтд. | Cytidine diphosphate choline crystal and method for its production |
| CN107049958A (en) * | 2017-04-26 | 2017-08-18 | 四川制药制剂有限公司 | The preparation technology of cefotaxime sodium for injection powder-injection |
| CN108096198A (en) * | 2017-12-26 | 2018-06-01 | 金华智济药物科技合伙企业（有限合伙） | Novel antibacterial pharmaceutical composition when prevention and treatment aerobic bacteria and anaerobic bacteria mixed infection and preparation method thereof |
| CN108409753A (en) * | 2018-04-08 | 2018-08-17 | 天津大学 | A kind of preparation method of Cefotaxime Sodium sphaerocrystal |
| CN112442048A (en) * | 2020-11-10 | 2021-03-05 | 华北制药河北华民药业有限责任公司 | Preparation method of cefpiramide sodium |
| CN112480145A (en) * | 2020-12-09 | 2021-03-12 | 山东鲁抗医药股份有限公司 | Preparation method of cefotaxime sodium |
| CN113666947A (en) * | 2021-07-23 | 2021-11-19 | 无锡海伦生物科技有限公司 | Preparation method of cefotaxime sodium |
| CN114028336A (en) * | 2021-10-20 | 2022-02-11 | 华北制药河北华民药业有限责任公司 | Preparation method of cefotaxime sodium for injection |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103319504A (en) | Crystallization method for cefotaxime sodium | |
| CN105330627B (en) | The method that high selectivity prepares SMIA | |
| CN102925526B (en) | Preparation method for 6-amino penicillanic acid | |
| CN110423241B (en) | Process for preparing cephalosporin C sodium salt and 7-aminocephalosporanic acid | |
| CN102690266B (en) | Method for preparing ertapenem sodium | |
| CN110156655B (en) | Method for preparing microalgae beta-carotene by using ultrasonic-assisted hydrophilic-hydrophobic two-phase system | |
| CN103275151B (en) | A kind of process for purification of Matachrom | |
| CN103420979A (en) | Esomeprazole sodium refining method | |
| CN103275153B (en) | A kind of preparation method of fidaxomicin crystal | |
| EP3385390B1 (en) | A method for preparing high transparent low acyl gellan gum | |
| CN106399446B (en) | Method for preparing amoxicillin by using deesterified liquid | |
| CN101811979B (en) | Technology for producing injection-grade terramycin | |
| CN102304137A (en) | Method for producing artesunate | |
| CN114149477A (en) | Crystallization method of high-purity vitamin B12 crystal and product thereof | |
| CN110330447B (en) | Preparation method and application of nafamostat mesylate intermediate | |
| CN105315300A (en) | Cefoxitin sodium, preparation method and uses thereof | |
| CN103408638B (en) | A kind of preparation technology of vancomycin crystallization | |
| CN102989505B (en) | Preparation method of redox mediator | |
| CN101550144B (en) | Preparation technique for mezlocillin | |
| CN102977102A (en) | Preparation method of meropenem trihydrate crystal | |
| CN117126403B (en) | Synthesis method of methyl MQ silicon resin | |
| CN106520893B (en) | Method for preparing ampicillin from penicillin potassium | |
| CN113121646B (en) | Method for preparing polymyxin methanesulfonic sodium by crystallization process | |
| CN109535184B (en) | Method for preparing potassium clavulanate from clavulanic acid tert-octylamine | |
| CN115814455A (en) | Crystallization method of sodium ascorbate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130925 |