CN104945418A - Children ampicillin sodium compound entity and pharmaceutical preparation thereof - Google Patents
Children ampicillin sodium compound entity and pharmaceutical preparation thereof Download PDFInfo
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- CN104945418A CN104945418A CN201510282127.1A CN201510282127A CN104945418A CN 104945418 A CN104945418 A CN 104945418A CN 201510282127 A CN201510282127 A CN 201510282127A CN 104945418 A CN104945418 A CN 104945418A
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- ampicillin
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/21—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring with a nitrogen atom directly attached in position 6 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D499/44—Compounds with an amino radical acylated by carboxylic acids, attached in position 6
- C07D499/48—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical
- C07D499/58—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical
- C07D499/64—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms
- C07D499/68—Compounds with an amino radical acylated by carboxylic acids, attached in position 6 with a carbon chain, substituted by hetero atoms or by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, attached to the carboxamido radical substituted in alpha-position to the carboxamido radical by nitrogen atoms with aromatic rings as additional substituents on the carbon chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D499/04—Preparation
- C07D499/14—Preparation of salts
- C07D499/16—Preparation of salts of alkali or alkaline earth metals
Abstract
The present invention discloses a children ampicillin sodium compound entity, wherein the preparation method comprises: (1) adding ampicillin to a mixed solution of dichloromethane and triethylamine, cooling, adding a small amount of a sodium 2-ethylhexanoate solution, increasing the solution temperature, adding the remaining sodium 2-ethylhexanoate solution, carrying out suction filtration, washing, and carrying out vacuum drying to obtain an ampicillin sodium crude product; (2) dissolving the ampicillin sodium crude product in purified water, adding active carbon, carrying out stirring decolorizing, and filtering; (3) adding an extractant to the filtrate under the stirring, transferring and filling into a pressure resistance container, removing air bubbles, carrying out sealing oscillation, carrying out temperature control freezing, and taking out; and (4) carrying out liquid-solid separation, discarding the extractant, adding acetone in a dropwise manner at a temperature of 5 DEG C after the solid melts, stirring at a slow speed, growing the grain, filtering, washing, and carrying out vacuum drying to obtain the ampicillin sodium finished product. The children ampicillin sodium compound entity of the present invention has advantages of good solubility, good clarity, low related substance content, good stability, low toxic-side effect, and the like.
Description
Technical field
The present invention relates to a kind of children's with ampicillin chemical entities and pharmaceutical preparation thereof, belong to medical compounds field.
Background technology
Ampicillin, chemistry is by name: (2S, 5R, 6R)-3,3-dimethyl-6 [(R)-2-amino-2-phenylacetyl amido]-7-oxo-4-sulfo--1-ammonia to mix dicyclo [3.2.0] heptane-2-potassium acid sodium-salt.Molecular formula: C
16h
18n
3naO
4s, molecular weight: 371.39.Ampicillin is a kind of semi-synthetic penicillins microbiotic applied the earliest, is applicable to treat the infection caused by sensitive bacterial.Typical indication comprises: the upper and lower respiratory tract infection such as sinusitis paranasal sinusitis, otitis media, epiglottitis, bacterial pneumonia; Urinary tract infections, pyelonephritis; The intra-abdominal infection such as peritonitis, cholecystitis, endometritis, pelvicellulitis; Bacillary microbemia; Skin, soft tissue, bone, the infection of joint; Gonococcal infection.
Chinese patent 200410008807.6 discloses a kind of method preparing ampicillin newly, comprise the following steps: by Ampicillin Trihydrate three water acid dissolve in dehydrated alcohol, react with two Isopropylamine again, react after reaction solution purifying with purified Sodium isooctanoate, reaction solution is crystallization in crystallizer, is filtered by gained crystallisate, washs, is drying to obtain ampicillin finished product.But the ampicillin of preparation still shows less stable, all unstable to heat, meta-acid environment, meta-alkali environment, show that outward appearance is easy to change, content reduces, occurs the problems such as degraded product, the reason of appearance may be the partial impurities cannot removed by the crystallization impact in ampicillin finished product.Therefore, high purity is prepared and stable ampicillin is those skilled in the art always makes great efforts.
Summary of the invention
The object of this invention is to provide a kind of children's and use ampicillin chemical entities, make children's have the advantages such as solvability is good, clarity is good, its related substances is low, good stability, toxic side effect are little with ampicillin chemical entities.
For solving the problems of the technologies described above, a kind of children's of the present invention uses ampicillin chemical entities, its structure as shown in formula I,
As preferably, described Ampicillin Trihydrate sodium compound is prepared by following steps:
(1) methylene dichloride and triethylamine is added in the reactor, stir, cool to 0 DEG C, add Ampicillin Trihydrate, be stirred to and dissolve completely, solution is degerming through membrane filtration, is cooled to-5 DEG C ~-10 DEG C, add a small amount of methyl acetate solution containing Sodium isooctanoate under fast stirring, stir after 10 minutes, slowly improve solution temperature to 10 ~ 15 DEG C while stirring, stir 30 minutes, keep temperature, slowly add remaining sodium iso-octoate solution again, continue stirring 2 hours, suction filtration, filter cake methyl acetate washs, and vacuum-drying obtains ampicillin crude product;
(2) ampicillin crude product is dissolved in purified water, adds gac, stir decolouring, filter;
(3) under agitation add extraction agent in filtrate, be transferred to and be full of in pressure vessel, remove sealing vibration after bubble, the freezing rear taking-up of temperature control;
(4) by solid-liquor separation, discard extraction agent, solid drips acetone at 5 DEG C, low rate mixing, growing the grain after melting, and filters, and washing, vacuum-drying, obtains ampicillin finished product.
As preferably, in described step (1), the weight ratio of Ampicillin Trihydrate and methylene dichloride is 1:3.5, and the weight of triethylamine is 45% of Ampicillin Trihydrate, and the weight ratio of methyl acetate and Sodium isooctanoate is 4:1, and the weight of Sodium isooctanoate is 70% of Ampicillin Trihydrate.
As preferably, in described step (1), sodium iso-octoate solution first time add-on is 1 ~ 3% of sodium iso-octoate solution total amount, and vacuum-drying temperature is 45 DEG C, and vacuum-drying pressure is-0.09MPa, and the vacuum-drying time is 5 ~ 6 hours.
As preferably, in described step (2), ampicillin strength of solution is 0.1 ~ 0.3g/ml, and activated carbon dosage is 3 ~ 10% of ampicillin crude product.
As preferably, in described step (3), extraction agent is several mixture of ethyl acetate, chloroform, ether or more.
As preferably, in described step (3), extraction agent is 1:100 ~ 200 with the volume ratio of the middle purified water of step (2).
As preferably, in described step (3), temperature control freezing temp is-20 ~-10 DEG C, and freezing time is 2 ~ 8 hours.
As preferably, in described step (4), the dripping quantity of acetone is 3 ~ 5 times of purified water consumption, and the low rate mixing time is 30 minutes, and rearing crystal time is 1 hour.
Present invention also offers and a kind ofly comprise the pharmaceutical preparation of above-mentioned children's with ampicillin chemical entities, described preparation is formed by ampicillin chemical entities and highly purified sulbactam Homogeneous phase mixing, the weight ratio of ampicillin and sulbactam is 2:1, and described preparation is powder injection.
A kind of children's of the present invention with the beneficial effect of ampicillin chemical entities and pharmaceutical preparation thereof is:
(1) by methylene dichloride, triethylamine, methyl acetate solvent, make amoxycilline Trihydrate bp and Sodium isooctanoate at-5 DEG C ~-10 DEG C, can prevent or reduce crystallization reaction, reduce the impurity in crystallization.Sodium iso-octoate solution add-on is 1 ~ 3% of sodium iso-octoate solution total amount for the first time, Tc is 10-15 DEG C, can make that the crystal purity that obtains is high, impurity is low, and can as the crystal seed of crystallization below, it is high that the ampicillin that crystallization can be made to obtain has purity, impurity is few, good stability, is not easy the advantages such as irritated.
(2) ampicillin crude product is dissolved in purified water, with activated carbon decolorizing, and can remove portion impurity.
(3) Ampicillin Trihydrate sodium solution under agitation extracts with immiscible with it and also immiscible with water extraction agent, dissolve organic contaminants can be removed in extraction agent, improves the purity of ampicillin.
(4) mixing solutions be transferred to and be full of in pressure vessel, after removing bubble, sealing is vibrated, carry out temperature control freezing, in refrigerating process, aqueous solvent is frozen into ice, and volumetric expansion increases, and the internal pressure in airtight pressure vessel is increased, thus the solubleness of the organic impurity that improve in ampicillin in extraction agent, reduce the foreign matter content in ampicillin finished product.
(5) aqueous solvent is frozen in the process of ice, and organic impurity is extruded from ice, further increases extraction efficiency, reduces foreign matter content.
(6) powder injection prepared with ampicillin chemical entities of children's provided by the invention, has solvability good, clarity good (without small particles phenomenon), good stability, the advantages such as impurity is low, and toxic side effect is little.
Embodiment
Below in conjunction with specific embodiment, embodiment of the present invention are described in detail.Should be appreciated that enforcement of the present invention is not limited to the following examples, any pro forma accommodation make the present invention and/or change all will fall into protection scope of the present invention.
Embodiment 1
Add 527ml methylene dichloride and 123ml triethylamine in the reactor, stir, cool to 0 DEG C, add 200 grams, Ampicillin Trihydrate, be stirred to and dissolve completely.Solution is after membrane filtration is degerming, and pipeline, merging filtrate and the washing lotion of Ampicillin Trihydrate process during mixed liquid washing and filtering with 260ml methylene dichloride and 16ml triethylamine.
In 609ml methyl acetate, add 140 grams of Sodium isooctanoates, be stirred to and dissolve completely.Solution after membrane filtration is degerming, and by pipeline, merging filtrate and the washing lotion of Sodium isooctanoate process during 200ml methyl acetate washing and filtering.
Ampicillin Trihydrate solution is cooled to-5 DEG C, under fast stirring, add the sodium iso-octoate solution of 1%, stir after 10 minutes, slowly improve solution temperature to 15 DEG C while stirring, stir 30 minutes, be incubated 15 DEG C, slowly add remaining sodium iso-octoate solution again, after adding sodium iso-octoate solution, continue stirring 2 hours, suction filtration, filter cake 500ml methyl acetate (degerming after filtration) points of 3 times washings, wet feed in 45 DEG C, dry 5 hours of-0.09MPa, obtains ampicillin crude product 168 grams in vacuum drying oven.
Take ampicillin crude product 100g, add purified water 1000ml, being warming up to 30 DEG C to all dissolving, adding 10g gac, stir decolouring, filter and obtain filtrate.
Under agitation in above-mentioned filtrate, add 5ml ethyl acetate, be transferred in 1000ml pressure vessel, guarantee to be full of and bubble removal, sealed vessel, vibration, takes out after the freezing 2h of temperature control-20 DEG C.
By solid-liquor separation, discard ethyl acetate solution, after ice-out, be transferred to crystallizer, within at 5 DEG C about 1 hour, drip 5000ml acetone, low rate mixing 30min, continue growing the grain 1h, suction filtration, with washing with acetone, obtain ampicillin finished product after vacuum-drying, purity is 99.93%.
Embodiment 2
Add 527ml methylene dichloride and 123ml triethylamine in the reactor, stir, cool to 0 DEG C, add 200 grams, Ampicillin Trihydrate, be stirred to and dissolve completely.Solution is after membrane filtration is degerming, and pipeline, merging filtrate and the washing lotion of Ampicillin Trihydrate process during mixed liquid washing and filtering with 260ml methylene dichloride and 16ml triethylamine.
In 609ml methyl acetate, add 140 grams of Sodium isooctanoates, be stirred to and dissolve completely.Solution after membrane filtration is degerming, and by pipeline, merging filtrate and the washing lotion of Sodium isooctanoate process during 200ml methyl acetate washing and filtering.
Ampicillin Trihydrate solution is cooled to-8 DEG C, under fast stirring, add the sodium iso-octoate solution of 2%, stir after 10 minutes, slowly improve solution temperature to 12 DEG C while stirring, stir 30 minutes, be incubated 12 DEG C, slowly add remaining sodium iso-octoate solution again, after adding sodium iso-octoate solution, continue stirring 2 hours, suction filtration, filter cake 500ml methyl acetate (degerming after filtration) points of 3 times washings, wet feed in 45 DEG C, dry 5.5 hours of-0.09MPa, obtains ampicillin crude product 168 grams in vacuum drying oven.
Take ampicillin crude product 100g, add purified water 500ml, being warming up to 30 DEG C to all dissolving, adding 7g gac, stir decolouring, filter and obtain filtrate.
Under agitation in above-mentioned filtrate, add 5ml chloroform, be transferred in 500ml pressure vessel, guarantee to be full of and bubble removal, sealed vessel, vibration, takes out after the freezing 5h of temperature control-15 DEG C.
By solid-liquor separation, discard chloroformic solution, after ice-out, be transferred to crystallizer, within at 5 DEG C about 1 hour, drip 2000ml acetone, low rate mixing 30min, continue growing the grain 1h, suction filtration, with washing with acetone, obtain ampicillin finished product after vacuum-drying, purity is 99.95%.
Embodiment 3
Add 527ml methylene dichloride and 123ml triethylamine in the reactor, stir, cool to 0 DEG C, add 200 grams, Ampicillin Trihydrate, be stirred to and dissolve completely.Solution is after membrane filtration is degerming, and pipeline, merging filtrate and the washing lotion of Ampicillin Trihydrate process during mixed liquid washing and filtering with 260ml methylene dichloride and 16ml triethylamine.
In 609ml methyl acetate, add 140 grams of Sodium isooctanoates, be stirred to and dissolve completely.Solution after membrane filtration is degerming, and by pipeline, merging filtrate and the washing lotion of Sodium isooctanoate process during 200ml methyl acetate washing and filtering.
Ampicillin Trihydrate solution is cooled to-10 DEG C, under fast stirring, add the sodium iso-octoate solution of 3%, stir after 10 minutes, slowly improve solution temperature to 10 DEG C while stirring, stir 30 minutes, be incubated 10 DEG C, slowly add remaining sodium iso-octoate solution again, after adding sodium iso-octoate solution, continue stirring 2 hours, suction filtration, filter cake 500ml methyl acetate (degerming after filtration) points of 3 times washings, wet feed in 45 DEG C, dry 6 hours of-0.09MPa, obtains ampicillin crude product 168 grams in vacuum drying oven.
Take ampicillin crude product 100g, add purified water 350ml, being warming up to 30 DEG C to all dissolving, adding 3g gac, stir decolouring, filter and obtain filtrate.
Under agitation in above-mentioned filtrate, add 2.3ml ethyl acetate and 2.3ml chloroform mixed solvent, be transferred in 350ml pressure vessel, guarantee to be full of and bubble removal, sealed vessel, vibration, takes out after the freezing 8h of temperature control-10 DEG C.
By solid-liquor separation, discard the mixing solutions of ethyl acetate and chloroform, after ice-out, be transferred to crystallizer, within at 5 DEG C about 1 hour, drip 1050ml acetone, low rate mixing 30min, continue growing the grain 1h, suction filtration, with washing with acetone, obtain ampicillin finished product after vacuum-drying, purity is 99.92%.
Embodiment 4 (comparative example)
18.5kg Sodium isooctanoate is dissolved in 56.5kg ritalin, gained solution is filtered, the place passed through with solution during ritalin washing and filtering, filtrate and washing lotion are merged, the liquid after merging is placed in sterilisable chamber high level tank and saves backup at 4 DEG C.By 30kg Ampicillin Trihydrate three water acid dissolve in the mixing solutions of the two Isopropylamine of 45.522kg dehydrated alcohol and 21.381kg, to be dissolved completely after, be cooled to 2 DEG C, add gac, first de-carbon filters, then sterile filtration, collects filtrate; With the place that filtrate during dehydrated alcohol washing and filtering is passed through, collect washings; Merging filtrate and washings, be placed in sterilisable chamber crystallizer by the liquid after merging and save backup at 4 DEG C.
Stir the sodium iso-octoate solution in sterilisable chamber high level tank while join in crystallizer, in crystallizer, start crystallization produce, crystallization condition is: temperature 0 DEG C, stirs 80 minutes under the stirring velocity of 100 revs/min; ) that 10L ritalin is placed on sterilisable chamber high level tank through sterile filtration is for subsequent use; The crystallization of the generation in crystallizer filtered, with the ritalin wash crystallization powder in sterilisable chamber high level tank 2 times, filtrate and washing lotion reclaim, and the crystallisate after washing is drying to obtain ampicillin sodium salt.
Embodiment 5
The ampicillin that above-described embodiment 1-3 is prepared and highly purified sulbactam Homogeneous phase mixing; be 2:1 according to the weight ratio of ampicillin and sulbactam; under A level laminar flow, adopt screw filling machine to be divided in sterile vial by former medicine according to 0.75g/ bottle under nitrogen protection; the temperature that controls environment is 20 ~ 24 DEG C; humidity is less than 40%, obtains Ampicillin Sodium For Injection sulbactam powder injection.
Accelerated test
Get the ampicillin that the ampicillin be made up of embodiment 1-3 and embodiment 4 traditional technology produce at random each a collection of, temperature 40 DEG C, place 6 months under relative humidity 75% condition, respectively at the 1st, 2,3, sampling in June, investigate the projects such as appearance character, look level, content, related substance, and with 0 month results contrast, test-results is in table 1.
Table 1
Result shows: the ampicillin that the present invention prepares is in accelerated test, and proterties, solution colour, related substance etc. are without considerable change, and its stability is good, significantly better than the ampicillin of comparative example.
Claims (10)
1. children's uses an ampicillin chemical entities, it is characterized in that, the structure of this ampicillin chemical entities as shown in formula I,
2. children's according to claim 1 uses ampicillin chemical entities, it is characterized in that, described Ampicillin Trihydrate sodium compound is prepared by following steps:
(1) methylene dichloride and triethylamine is added in the reactor, stir, cool to 0 DEG C, add Ampicillin Trihydrate, be stirred to and dissolve completely, solution is degerming through membrane filtration, is cooled to-5 DEG C ~-10 DEG C, add a small amount of methyl acetate solution containing Sodium isooctanoate under fast stirring, stir after 10 minutes, slowly improve solution temperature to 10 ~ 15 DEG C while stirring, stir 30 minutes, keep temperature, slowly add remaining sodium iso-octoate solution again, continue stirring 2 hours, suction filtration, filter cake methyl acetate washs, and vacuum-drying obtains ampicillin crude product;
(2) ampicillin crude product is dissolved in purified water, adds gac, stir decolouring, filter;
(3) under agitation add extraction agent in filtrate, be transferred to and be full of in pressure vessel, remove sealing vibration after bubble, the freezing rear taking-up of temperature control;
(4) by solid-liquor separation, discard extraction agent, solid drips acetone at 5 DEG C, low rate mixing, growing the grain after melting, and filters, and washing, vacuum-drying, obtains ampicillin finished product.
3. children's according to claim 2 uses ampicillin chemical entities, it is characterized in that, in described step (1), the weight ratio of Ampicillin Trihydrate and methylene dichloride is 1:3.5, the weight of triethylamine is 45% of Ampicillin Trihydrate, the weight ratio of methyl acetate and Sodium isooctanoate is 4:1, and the weight of Sodium isooctanoate is 70% of Ampicillin Trihydrate.
4. children's according to claim 2 uses ampicillin chemical entities, it is characterized in that, in described step (1), sodium iso-octoate solution first time add-on is 1 ~ 3% of sodium iso-octoate solution total amount, vacuum-drying temperature is 45 DEG C, vacuum-drying pressure is-0.09MPa, and the vacuum-drying time is 5 ~ 6 hours.
5. children's according to claim 2 uses ampicillin chemical entities, it is characterized in that, in described step (2), ampicillin strength of solution is 0.1 ~ 0.3g/ml, and activated carbon dosage is 3 ~ 10% of ampicillin crude product.
6. children's according to claim 2 uses ampicillin chemical entities, it is characterized in that, in described step (3), extraction agent is several mixture of ethyl acetate, chloroform, ether or more.
7. children's according to claim 2 uses ampicillin chemical entities, it is characterized in that, in described step (3), the volume ratio of extraction agent and the middle purified water of step (2) is 1:100 ~ 200.
8. children's according to claim 2 uses ampicillin chemical entities, it is characterized in that, in described step (3), temperature control freezing temp is-20 ~-10 DEG C, and freezing time is 2 ~ 8 hours.
9. children's according to claim 2 uses ampicillin chemical entities, it is characterized in that, in described step (4), the dripping quantity of acetone is 3 ~ 5 times of purified water consumption, and the low rate mixing time is 30 minutes, and rearing crystal time is 1 hour.
10. one kind comprises the pharmaceutical preparation of children's as claimed in any of claims 1 to 9 with ampicillin chemical entities, it is characterized in that, described preparation is formed by ampicillin chemical entities and highly purified sulbactam Homogeneous phase mixing, the weight ratio of ampicillin and sulbactam is 2:1, and described preparation is powder injection.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105384755A (en) * | 2015-11-13 | 2016-03-09 | 山东鲁抗医药股份有限公司 | Refining method for improving purity of ampicillin sodium |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1666990A (en) * | 2004-03-12 | 2005-09-14 | 河北张药股份有限公司 | Process for preparing ampicillin sodium |
| CN101486717A (en) * | 2008-12-05 | 2009-07-22 | 华北制药股份有限公司 | Method for preparing ampicillin sodium |
| CN101723957A (en) * | 2008-10-24 | 2010-06-09 | 华北制药股份有限公司 | Method for preparing ampicillin sodium salt |
| CN102179063A (en) * | 2011-03-23 | 2011-09-14 | 苏州汇通色谱分离纯化有限公司 | High pressure liquid-liquid extraction method |
| CN103880863A (en) * | 2014-03-27 | 2014-06-25 | 哈药集团制药总厂 | Preparation method of ampicillin sodium |
| CN104644629A (en) * | 2015-01-27 | 2015-05-27 | 华北制药股份有限公司 | Ampicillin sodium sulbactam sodium preparation for injection and preparation method thereof |
-
2015
- 2015-05-28 CN CN201510282127.1A patent/CN104945418A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1666990A (en) * | 2004-03-12 | 2005-09-14 | 河北张药股份有限公司 | Process for preparing ampicillin sodium |
| CN101723957A (en) * | 2008-10-24 | 2010-06-09 | 华北制药股份有限公司 | Method for preparing ampicillin sodium salt |
| CN101486717A (en) * | 2008-12-05 | 2009-07-22 | 华北制药股份有限公司 | Method for preparing ampicillin sodium |
| CN102179063A (en) * | 2011-03-23 | 2011-09-14 | 苏州汇通色谱分离纯化有限公司 | High pressure liquid-liquid extraction method |
| CN103880863A (en) * | 2014-03-27 | 2014-06-25 | 哈药集团制药总厂 | Preparation method of ampicillin sodium |
| CN104644629A (en) * | 2015-01-27 | 2015-05-27 | 华北制药股份有限公司 | Ampicillin sodium sulbactam sodium preparation for injection and preparation method thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105384755A (en) * | 2015-11-13 | 2016-03-09 | 山东鲁抗医药股份有限公司 | Refining method for improving purity of ampicillin sodium |
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