CN105713012A - Cefamandole nafate refining method - Google Patents
Cefamandole nafate refining method Download PDFInfo
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- CN105713012A CN105713012A CN201610087754.4A CN201610087754A CN105713012A CN 105713012 A CN105713012 A CN 105713012A CN 201610087754 A CN201610087754 A CN 201610087754A CN 105713012 A CN105713012 A CN 105713012A
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- cefamandole nafate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/36—Methylene radicals, substituted by sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/02—Preparation
- C07D501/12—Separation; Purification
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- Cephalosporin Compounds (AREA)
Abstract
The invention provides a cefamandole nafate refining method. The method comprises the steps of A, dissolving polyvinylpyrrolidone in a lower alcohol and water mixed solvent to prepare a polyvinylpyrrolidone solution of 0.1-1.0 mol/L, then adding a cefamandole nafate crude product, increasing temperature to 50-80 DEG C, adding activated carbon after complete dissolution, conducting stirring for 10-30 min, and then conducting filtration to obtain a filtrate for use; B, adding sodium iso-octoate of 15% to the filtration obtained in the step A dropwise, and regulating pH to 6.0-7.0, so that a cefamandole nafate crude product solution is obtained; C, adding acetone to the cefamandole nafate crude product solution obtained in the step B dropwise while stirring, then conducting ultrasonic treatment for 10-30 min, continuing to add acetone, conducting stirring at indoor temperature for 1-2 h to enable a large number of crystals to be separated out, conducting filtration, conducting washing with a small amount of ethyl alcohol, and conducting vacuum drying so that a cefamandole nafate refined product can be obtained, wherein the amount of acetone added at the second time is 0.8-1.2 times that of acetone added at the first time. The refining method has the advantages that yield and purity are high, and the product is high in stability and light in color.
Description
Technical field
The processing method that the present invention relates to a kind of cefamandole nafate, is specifically related to the essence of a kind of cefamandole nafate
Method processed.
Background technology
Cefamandole nafate (Cefamandol Nafate) is second generation cephalosporin class antibiotic, initially by U.S.
State's E.Lilly Developed, chemical name is: 7-D-(2-methanoyl phenyl acetamide)-3-[(1-methyl isophthalic acid H-
Tetrazolium-5-base) thiopurine methyltransferase]-3-cephem-4-carboxylic acid sodium salt.Molecular formula is C19H17N6NaO6S2, molecular weight is
512.50, No. CAS is: 30034-03-8, and structural formula is as follows:
Cefamandole nafate is the cephalosporin that a kind of bactericidal action is stronger, has the first generation and third generation cephalo bacterium concurrently
Most of gram positive bacterias and part gram negative bacteria, clostridium are had powerful by the advantage of element
Antibacterial activity, particularly to hemophilus influenza, escherichia coli, proteus mirabilis, Proteus rettgeri,
The effect of Bacillus typhi, dysentery bacterium and pneumobacillus etc. is stronger than first generation cephalosporin.To various infectious diseases
Sick evident in efficacy, there is the features such as resistance to enzyme, low toxicity, blood drug level is high, tissue distribution is wide, side effect is little.
At present, use clinically for cefamandole nafate for injection, due to its Material synthesis technique and medicine
The chemical constitution impact on product stability, often containing more head in Mandokef sodium raw materials and formulation products
Spore many free acids in the Meng and other impurity, thus affect product quality, cause formulation products not clarify, turbidity does not conforms to
Lattice, and reduce the stability of preparation.
United States Patent (USP) US4351947 and European patent EP 0432297 provide effectively prepares Mandokef
The method of sodium, but target product purity is the highest, colour-difference, have impact on the quality of its preparation.Therefore, Hen Duoke
Grind unit and medicine enterprise develops all kinds of purification for cefamandole nafate and refined method.Such as, Chinese patent
CN201210126642.7 discloses a kind of method of preparation of fine cefamandole nafate, including by cefamandole nafate
Crude product is after salt-free water, the first organic solvent and Organic Sodium Salt mix, and the pH value controlling reaction system is
5.5-7.5 and temperature are 5-15 DEG C, add active carbon filtration, gained filtrate are mixed with the second organic solvent
Even, separate out crystal, obtain described cefamandole nafate.Patent CN201310011433.2 uses mixing organic
Solvent as good solvent, obtains the Mandokef that color is preferable, purity is higher as poor solvent, injection water
Sodium product, but yield is relatively low.
Purification process disclosed in prior art, although can solve the problem that above-mentioned color and purity are asked to a certain extent
Topic, but still described problem can not be fully solved.Therefore, also need to seek more preferably scheme to solve prior art
In problem.
Summary of the invention
It is an object of the invention to overcome the deficiency of existing cefamandole nafate process for purification, it is provided that a kind of yield
Cefamandole nafate process for purification high, that purity is high, color is good, by the cefamandole nafate that this method is refined
Product colour conforms to quality requirements, good stability, and impurity content is low；Meanwhile, the method for the present invention is simple to operate,
Be conducive to industrialized production.
The invention provides the process for purification of a kind of cefamandole nafate, the method comprises the following steps:
A, polyvinylpyrrolidone is dissolved in the mixed solvent of lower alcohol and water, is made into 0.1-1.0mol L-1
Polyvinylpyrrolidonesolution solution, be subsequently adding cefamandole nafate crude product, be heated to 50-80 DEG C, the most molten
Xie Hou, adds activated carbon, after stirring 10-30min, and filtered while hot, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 6.0-7.0, obtain cephalo
The Meng polyester sodium crude product solution；
Under C, stirring, acetone is dropped to the cefamandole nafate crude product solution described in step B, drip and finish, super
Sound 10-30min, continuously adds acetone, is stirred at room temperature 1-2h, separates out a large amount of solid, filters, with few
Amount washing with alcohol, vacuum drying, obtain cefamandole nafate fine work；Wherein second time adds the amount of acetone is the
0.8-1.2 times once.
Those skilled in the art can use common filtration under diminished pressure and drying process to enter cefamandole nafate fine work
Row processes, such as, can carry out vacuum drying etc. at 40 DEG C-50 DEG C.
Cause subpackage difficulty due to the Mandokef sodium raw materials easily moisture absorption, and its semi-synthetic crude material contains
Having a small amount of organic impurities, reaction intermediate etc., Clinical practice can cause the untoward reaction such as drug allergy, Er Qieyuan
Material crude product color is relatively deep, and stability is bad.Cefamandole nafate crude product is refined by the present invention, miscellaneous to reduce
Matter content, improves drug safety, reduces untoward reaction.Inventor finds, uses the present processes to refine
Cefamandole nafate can effectively reduce impurity content, and product colour is shallow, good stability, and yield is high simultaneously.
According to the process for purification of the present invention, wherein, described lower alcohol can be methanol, ethanol or isopropanol, can
With preferably ethanol.
According to the process for purification of the present invention, wherein, described in step A, lower alcohol is selected from: methanol, ethanol, different
Propanol；Preferential ethanol；Described lower alcohol with the volume ratio of water is: 5:1-3:1；The most described lower alcohol and water
Volume ratio is 4:1.
According to the process for purification of the present invention, wherein cefamandole nafate crude product consumption and described poly-second in step A
The mass volume ratio of alkene pyrrolidone solution is 1:3-1:5.Preferably 1:4.
According to the process for purification of the present invention, wherein ultrasonic described in step C power is 0.4-0.5kw；
According to the process for purification of the present invention, wherein in step C, twice acetone consumption volume summation is cefamandole
6-8 times of ester sodium crude product quality.
Process for purification according to the present invention, it is characterised in that the polyvinylpyrrolidonesolution solution concentration in step A
For 0.1-1.0mol L-1, preferably 0.2-0.4mol L-1。
The process for purification of the cefamandole nafate of the present invention, has the advantages that
1, relative to cefamandole nafate crude product, the process for purification of the present invention is used and the Mandokef prepared
Sodium has the cefamandole free acid of lower loading and higher purity, and color is more shallow.And the product of the present invention
Product can reach 99.9% in purity, and yield is up to more than 90%, good stability.
Cefamandole nafate solution clarity the most provided by the present invention is good, constant product quality simultaneously.Through adding
Speed and long-term stable experiment are investigated and are shown, the cefamandole nafate of the present invention is placed up to 2 under holding conditions
Year, every quality index has no significant change.
Detailed description of the invention
Further illustrating the present invention below by specific embodiment, these embodiments are only for the most concrete
Ground explanation, and it is not to be construed as limiting in any form the present invention.
Embodiment 1
A, polyvinylpyrrolidone is dissolved in methanol: in the mixed solvent of water=5:1, be made into 0.2mol L-1's
Polyvinylpyrrolidonesolution solution 30ml, is subsequently adding cefamandole nafate crude product 10g (Mandokef sodium content
Being 89%, free acid content is 5.5%), it is heated to 50 DEG C, after being completely dissolved, adds activated carbon, stirring
After 10min, filter, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 6.5, obtain cefamandole
Ester sodium crude product solution；
Under C, stirring, 30ml acetone is dropped to the cefamandole nafate crude product solution described in step B, drip
Finish, ultrasonic 10min, continuously add acetone 30ml, be stirred at room temperature 2h, separate out a large amount of crystal, filter,
Use a small amount of washing with alcohol, vacuum drying, obtain cefamandole nafate fine work 9.19g (yield 91.9%).
Detection: color level is No. 1, and HPLC purity is 99.8%, cefamandole nafate educt 0.16%.
Embodiment 2
A, polyvinylpyrrolidone is dissolved in ethanol: in the mixed solvent of water=4:1, be made into 0.3mol L-1's
Polyvinylpyrrolidonesolution solution 40ml, is subsequently adding cefamandole nafate crude product 10g (Mandokef sodium content
Being 89%, free acid content is 5.5%), it is heated to 80 DEG C, after being completely dissolved, adds activated carbon, stirring
After 30min, filter, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 7.0, obtain cefamandole
Ester sodium crude product solution；
Under C, stirring, 40ml acetone is dropped to the cefamandole nafate crude product solution described in step B, drip
Finish, ultrasonic 10min, continuously add acetone 40ml, be stirred at room temperature 1.5h, separate out a large amount of crystal, mistake
Filter, uses a small amount of washing with alcohol, vacuum drying, obtains cefamandole nafate fine work 9.42g (yield 94.2%).
Detection: color level is less than No. 1, and HPLC: purity is 99.9%, cefamandole nafate educt 0.08%.
Embodiment 3
A, polyvinylpyrrolidone is dissolved in isopropanol: in the mixed solvent of water=3:1, be made into 0.4mol L-1
Polyvinylpyrrolidonesolution solution 50ml, (cefamandole nafate contains to be subsequently adding cefamandole nafate crude product 10g
Amount is 89%, and free acid content is 5.5%), it is heated to 65 DEG C, after being completely dissolved, adds activated carbon, stir
After mixing 30min, filter, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 6.8, obtain cefamandole
Ester sodium crude product solution；
Under C, stirring, 35ml acetone is dropped to the cefamandole nafate crude product solution described in step B, drip
Finish, ultrasonic 30min, continuously add acetone 35ml, be stirred at room temperature 2h, separate out a large amount of crystal, filter,
Use a small amount of washing with alcohol, vacuum drying, obtain cefamandole nafate fine work 9.28g (92.8%).
Detection: color level is No. 1, and HPLC purity is 99.8%, cefamandole nafate educt 0.13%.
Embodiment 4
A, polyvinylpyrrolidone is dissolved in ethanol: in the mixed solvent of water=4:1, be made into 0.3mol L-1's
Polyvinylpyrrolidonesolution solution 30ml, is subsequently adding cefamandole nafate crude product 10g (Mandokef sodium content
Being 89%, free acid content is 5.5%), it is heated to 75 DEG C, after being completely dissolved, adds activated carbon, stirring
After 30min, filter, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 6.5, obtain cefamandole
Ester sodium crude product solution；
Under C, stirring, 40ml acetone is dropped to the cefamandole nafate crude product solution described in step B, drip
Finish, ultrasonic 15min, continuously add acetone 40ml, be stirred at room temperature 1.5h, separate out a large amount of crystal, mistake
Filter, uses a small amount of washing with alcohol, vacuum drying, obtains cefamandole nafate fine work 9.41g (94.1%).
Detection: color level is less than No. 1, and HPLC purity is 99.9%, cefamandole nafate educt 0.07%.
Embodiment 5
A, polyvinylpyrrolidone is dissolved in methanol: in the mixed solvent of water=4:1, be made into 0.4mol L-1's
Polyvinylpyrrolidonesolution solution 40ml, is subsequently adding cefamandole nafate crude product 10g (Mandokef sodium content
Being 89%, free acid content is 5.5%), it is heated to 80 DEG C, after being completely dissolved, adds activated carbon, stirring
After 30min, filter, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 6.5, obtain cefamandole
Ester sodium crude product solution；
Under C, stirring, 35ml acetone is dropped to the cefamandole nafate crude product solution described in step B, drip
Finish, ultrasonic 10min, continuously add acetone 36ml, be stirred at room temperature 1.5h, separate out a large amount of crystal, mistake
Filter, uses a small amount of washing with alcohol, vacuum drying, obtains cefamandole nafate fine work 9.33g (93.3%).
Detection: color level is less than No. 2, and HPLC purity is 99.86%, cefamandole nafate educt 0.12%.
Comparative example 1:
A, by methanol: water=5:1 prepares mixed solvent 30ml, is subsequently adding cefamandole nafate crude product 10g (head
Spore polyester in Meng sodium content is 89%, and free acid content is 5.5%), it is heated to 50 DEG C, after being completely dissolved, adds
Enter activated carbon, after stirring 10min, filter, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 6.5, obtain cefamandole
Ester sodium crude product solution；
Under C, stirring, 30ml acetone is dropped to the cefamandole nafate crude product solution described in step B, drip
Finish, ultrasonic 10min, continuously add acetone 30ml, be stirred at room temperature 2h, separate out crystal, filter, use
A small amount of washing with alcohol, vacuum drying, obtain cefamandole nafate fine work 8.5g (yield 85%).
Detection: color level is that < No. 3, HPLC purity is 96.8%.
Comparative example 2:
A, by ethanol: water=4:1 prepares mixed solvent 40ml, is subsequently adding cefamandole nafate crude product 10g (head
Spore polyester in Meng sodium content is 89%, and free acid content is 5.5%), it is heated to 80 DEG C, after being completely dissolved, adds
Enter activated carbon, after stirring 30min, filter, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 7.0, obtain cefamandole
Ester sodium crude product solution；
Under C, stirring, 40ml acetone is dropped to the cefamandole nafate crude product solution described in step B, drip
Finish, ultrasonic 10min, continuously add acetone 40ml, be stirred at room temperature 1.5h, separate out a large amount of crystal, mistake
Filter, uses a small amount of washing with alcohol, vacuum drying, obtains cefamandole nafate fine work 8.62g (yield 86.2%).
Detection: color level is No. 3, and HPLC: purity is 96.9%.
From the comparison of above-mentioned comparative example and the application it can be seen that add polyvinylpyrrolidone and unexpectedly carry
The purity of high cefamandole nafate and yield.
Test example 1
This test example is for illustrating to use the stability of the cefamandole nafate fine work of process for purification of the present invention acquisition.
Three batch samples that Example 2 prepares, be accelerated respectively according to medicine stability test guideline and
Long-term stable experiment, result of the test is shown in Table 1 respectively, table 2.
Table 1 accelerated stability test result data
Table 2 long-term stable experiment result data
Data above shows, by accelerating 6 months and the stability test of long-term 24 months, the head of the present invention
Spore polyester in Meng sodium color, having related substance and purity, clarity does not all occur significantly to change, therefore by this
Cefamandole nafate constant product quality prepared by bright process for purification is good.
Test example 2:
Carry out following experiments as described in Example 2, except ratio or the polyvinylpyrrolidoneconcentration concentration of ethanol and water
Difference, other operation is the most identical, result such as table 3, table 4:
The ratio of table 3, different lower alcohols and water is on yield and the impact of purity
| Group | Ethanol: water | Yield (%) | Purity (%) |
| 1 | 2:1 | 87.12 | 97.82 |
| 2 | 3:1 | 92.31 | 99.89 |
| 3 | 4:1 | 93.91 | 99.90 |
| 4 | 5:1 | 93.21 | 99.88 |
| 5 | 6:1 | 89.12 | 98.56 |
| 6 | 7:1 | 88.36 | 98.78 |
Table 4, different polyvinylpyrrolidoneconcentration concentration are on yield and the impact of purity
From above-mentioned table 3, table 4 it can be seen that the application is for the ratio of ethanol and water and polyvinylpyrrolidine
The selection of ketone concentration effectively raises yield and the purity of cefamandole nafate.
Although present invention has been a certain degree of description, it will be apparent that, without departing from the spirit of the present invention and model
Under conditions of enclosing, the suitable change of each condition can be carried out.It is appreciated that and the invention is not restricted to described embodiment party
Case, and it is attributed to the scope of claim, it includes the equivalent of described each factor.
Claims (5)
1. the process for purification of a cefamandole nafate, it is characterised in that comprise the following steps:
A, polyvinylpyrrolidone is dissolved in the mixed solvent of lower alcohol and water, is made into 0.1-1.0mol L-1Polyvinylpyrrolidonesolution solution, be subsequently adding cefamandole nafate crude product, be heated to 50-80 DEG C, after being completely dissolved, add activated carbon, stirring 10-30min after, filter, obtain filtrate, standby；
B, in the filtrate of step A drip 15% Sodium isooctanoate., regulate pH to 6.0-7.0, obtain cefamandole nafate crude product solution；
Under C, stirring, acetone is dropped to the cefamandole nafate crude product solution described in step B, drip and finish, ultrasonic 10-30min, continuously add acetone, be stirred at room temperature 1-2h, separate out a large amount of crystal, filter, use a small amount of washing with alcohol, vacuum drying, obtain cefamandole nafate fine work；Wherein 0.8-1.2 times that amount is consumption for the first time of second time addition acetone.
Process for purification the most according to claim 1, it is characterised in that described in step A, lower alcohol is selected from: methanol, ethanol, isopropanol；Described lower alcohol with the volume ratio of water is: 5:1-3:1；.
3. according to the process for purification of claim 1 or 2, it is characterised in that: in step A, cefamandole nafate crude product consumption is 1:3-1:5 with the mass volume ratio of described polyvinylpyrrolidonesolution solution.
4. according to the process for purification of claim 1-3, it is characterised in that: power ultrasonic described in step C is 0.4-0.5kw；Twice acetone consumption volume summation is 6-8 times of cefamandole nafate crude product quality.
5. according to the process for purification of claim 1-4, it is characterised in that the polyvinylpyrrolidonesolution solution concentration in step A is 0.2-0.4mol L-1。
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4351947A (en) * | 1980-03-06 | 1982-09-28 | Asahi Chemical Industry Co., Ltd. | Tetrazole derivative |
| EP0432297A1 (en) * | 1989-12-13 | 1991-06-19 | Technologitschen Kombinat Sa Promischlena Mikrobiologia | A method for the preparation of the sodium salt of O-formyl cefamandole |
| CN101108856A (en) * | 2007-07-27 | 2008-01-23 | 苏州中联化学制药有限公司 | Method for synthesizing antibiotic cefamandole nafate |
| CN102351886A (en) * | 2011-09-07 | 2012-02-15 | 山东罗欣药业股份有限公司 | Cefteram pivoxil crystal and preparation method thereof and composition tablets containing crystal |
| CN102702232A (en) * | 2012-04-17 | 2012-10-03 | 山东鲁抗医药股份有限公司 | Method for preparation of fine cefamandole nafate |
| CN103044453A (en) * | 2013-01-22 | 2013-04-17 | 湖北济生医药有限公司 | Cefamandole nafate compound and pharmaceutical composition thereof |
| CN103145736A (en) * | 2013-03-29 | 2013-06-12 | 四川省惠达药业有限公司 | Medicine composite containing cefamandole nafate compound |
-
2016
- 2016-02-16 CN CN201610087754.4A patent/CN105713012A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4351947A (en) * | 1980-03-06 | 1982-09-28 | Asahi Chemical Industry Co., Ltd. | Tetrazole derivative |
| EP0432297A1 (en) * | 1989-12-13 | 1991-06-19 | Technologitschen Kombinat Sa Promischlena Mikrobiologia | A method for the preparation of the sodium salt of O-formyl cefamandole |
| CN101108856A (en) * | 2007-07-27 | 2008-01-23 | 苏州中联化学制药有限公司 | Method for synthesizing antibiotic cefamandole nafate |
| CN102351886A (en) * | 2011-09-07 | 2012-02-15 | 山东罗欣药业股份有限公司 | Cefteram pivoxil crystal and preparation method thereof and composition tablets containing crystal |
| CN102702232A (en) * | 2012-04-17 | 2012-10-03 | 山东鲁抗医药股份有限公司 | Method for preparation of fine cefamandole nafate |
| CN103044453A (en) * | 2013-01-22 | 2013-04-17 | 湖北济生医药有限公司 | Cefamandole nafate compound and pharmaceutical composition thereof |
| CN103145736A (en) * | 2013-03-29 | 2013-06-12 | 四川省惠达药业有限公司 | Medicine composite containing cefamandole nafate compound |
Non-Patent Citations (3)
| Title |
|---|
| 张颖，等: "头孢孟多酯钠制备工艺的改进", 《海峡药学》 * |
| 韩永龙，等: "聚乙烯吡咯烷酮在中药制剂中的应用", 《中医药学报》 * |
| 马祥志，等: "《有机化学》", 31 July 2014, 中国医药科技出版社 * |
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Application publication date: 20160629 |