CN104922678A - Child-type medicinal composition with ampicillin sulbactam sodium and low-sodium carrier - Google Patents
Child-type medicinal composition with ampicillin sulbactam sodium and low-sodium carrier Download PDFInfo
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- CN104922678A CN104922678A CN201510280357.4A CN201510280357A CN104922678A CN 104922678 A CN104922678 A CN 104922678A CN 201510280357 A CN201510280357 A CN 201510280357A CN 104922678 A CN104922678 A CN 104922678A
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Abstract
The invention relates to a child-type ampicillin-sulbactam-sodium medicinal composition, i.e. a medicinal combined preparation with ampicillin sulbactam sodium and low-sodium carrier infusion fluid, especially combined application package comprising the ampicillin sulbactam sodium and the low-sodium infusion carrier fluid. The low-sodium carrier infusion fluid comprises glucose and sodium chloride injection fluid (15-200:1) and glucose and sodium-chloride potassium-chloride injection fluid (15-200:1:0-1) and the like. The child-type medicinal composition has the advantages that compared with the compatible and mixing use of the ampicillin sulbactam sodium and the low-sodium carrier infusion fluid, the clinical application steps are simplified, the clinical risks caused by incapability of metabolizing excessive sodium in blood since the kidney of a child is not matured are reduced and the clinical application quality and safety of child administration are improved.
Description
Technical field
The present invention relates to a kind of child form ampicillin and sulbactam sodium and low sodium carrier pharmaceutical composition, belong to medicinal chemistry art.
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:
C16H18N3NaO4S, molecular weight: 371.39.Ampicillin is a kind of semi-synthetic penicillins antibiotic 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, otitis media, epiglottitis, bacterial pneumonia; Urinary tract infection, pyelonephritis; The intra-abdominal infection such as peritonitis, cholecystitis, endometritis, pelvicellulitis; Bacillary bacteremia; 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 three water acid dissolve in dehydrated alcohol, react with two 2-aminopropane. again, react after reactant liquor purification with purified Sodium isooctanoate., reactant liquor is crystallization in crystallizer, is filtered by gained crystal, 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 catabolite, the reason of appearance may be the partial impurities cannot removed by the crystallization impact in ampicillin finished product.Children's torso each side is still in growth stage, and the side effect that Drug-related causes can show particularly evident, controls Drug-related content in pediatric pharmaceuticals, seems particularly important.The purity how improving children's's ampicillin is current problem demanding prompt solution, has great Social benefit and economic benefit.Therefore, high-purity is prepared and stable ampicillin is those skilled in the art always makes great efforts.
Because child's kidney is not reached maturity, there is no sodium too much in ability metabolism blood.If hypernatremia, be difficult to recover to the injury of child, and the age is less, and to receive injury larger, particularly neonate.Neonate and infant kidney are poor to acid, alkali and water metabolism regulating power, and the filtration rate of glomerule is only adult's 1/4 ~ 1/2.
For the physiological characteristics of child, reduce the clinical risk that ampicillin is in use possible, invent and a kind ofly can meet the child form ampicillin and sulbactam sodium of child's stage physiological characteristics and low sodium carrier pharmaceutical composition, namely the carrier transfusion of low sodium is packed with ampicillin and sulbactam sodium Combination application.
Need in Clinical practice to buy use in conjunction respectively, the assembly packaging of the carrier flow of infusate combination preparation of ampicillin and sulbactam sodium and low sodium does not occur commercially with in medical institutions.
Summary of the invention
The object of this invention is to provide the medicine composition that a kind of child form ampicillin and sulbactam sodium pharmaceutical composition and ampicillin and sulbactam sodium and low sodium carrier are infused, especially Combination application packaging, with a kind of ampicillin and sulbactam sodium preparation method, it can solve above-mentioned shortcoming of the prior art.
For achieving the above object, the present invention is by the following technical solutions:
A kind of child form ampicillin and sulbactam sodium and low sodium carrier pharmaceutical composition are ampicillin and sulbactam sodium glucose sodium chloride potassium injection or ampicillin and sulbactam sodium Dextrose and Sodium Chloride Inj..
Preferably, this ampicillin and sulbactam sodium glucose sodium chloride potassium injection comprises each component of following quality:
Ampicillin and sulbactam sodium 0.25g-1.0g;
Glucose 5-9g;
Sodium chloride 0.1-0.2g;
Potassium chloride 0.1-0.2g;
Add water to 100mL.
This ampicillin and sulbactam sodium Dextrose and Sodium Chloride Inj. comprises each component of following quality:
Ampicillin and sulbactam sodium 0.25g-1.0g;
Glucose 5-9g;
Sodium chloride 0.1-0.2g;
Add water to 100mL.
Preferably, this pharmaceutical composition can be packed for Combination application.
Preferably, this ampicillin and sulbactam sodium is prepared by following steps:
(1) dichloromethane and triethylamine is added in the reactor, stir, cool to 0 DEG C, add ampicillin, 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, sucking filtration, filter cake methyl acetate washs, and vacuum drying obtains ampicillin crude product;
(2) ampicillin crude product is dissolved in purified water, adds active carbon, stir decolouring, filter;
(3) under agitation add extractant 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 extractant, solid drips acetone at 5 DEG C, low rate mixing, growing the grain after melting, and filters, washing, and vacuum drying, obtains ampicillin finished product;
(5) by obtained ampicillin and highly purified sulbactam sodium 2:1 Homogeneous phase mixing by weight.
As preferably, in described step (1), the weight ratio of ampicillin and dichloromethane is 1:3.5, and the weight of triethylamine is 45% of ampicillin, and the weight ratio of methyl acetate and Sodium isooctanoate. is 4:1, and the weight of Sodium isooctanoate. is 70% of ampicillin.
As preferably, in described step (1), sodium iso-octoate solution first time addition 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 solution concentration is 0.1 ~ 0.3g/ml, and activated carbon dosage is 3 ~ 10% of ampicillin crude product.
As preferably, in described step (3), extractant is several mixture of ethyl acetate, chloroform, ether or more.
As preferably, in described step (3), extractant is 1:100 ~ 200 with the volume ratio of the middle purified water of step (2).
As preferably, in described step (3), temperature control cryogenic temperature is-20 ~-10 DEG C, and cooling 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.
A kind of children's of the present invention with the beneficial effect of ampicillin and sulbactam sodium compound entity and pharmaceutical preparation thereof is:
(1) by dichloromethane, triethylamine, methyl acetate solvent, make amoxicillin 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 addition is 1 ~ 3% of sodium iso-octoate solution total amount for the first time, crystallization temperature 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 sodium solution under agitation extracts with immiscible with it and also immiscible with water extractant, dissolve organic contaminants can be removed in extractant, improves the purity of ampicillin.
(4) mixed solution 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 dissolubility of the organic impurities that improve in ampicillin in extractant, reduce the impurity content in ampicillin finished product.
(5) aqueous solvent is frozen in the process of ice, and organic impurities is extruded from ice, further increases extraction efficiency, reduces impurity content.
(6) injectable powder prepared with ampicillin chemical entities of children's provided by the invention, has dissolubility good, the advantages such as clarity is good, good stability, and impurity is low, and toxic and side effects is little.
(7) simultaneously, have employed the carrier flow of infusate assembly packaging of ampicillin and sulbactam sodium and low sodium, used in combination relative to the compatibility of the two, simplify step, improve the safety of children; Decrease because child's kidney is not reached maturity, there is no the clinical risk that in ability metabolism blood, too much sodium brings, improve the clinical practice quality of children.
Detailed description of the invention
Set forth the specific embodiment of the present invention further below:
Embodiment 1
Add 527ml dichloromethane and 123ml triethylamine in the reactor, stir, cool to 0 DEG C, add 200 grams, ampicillin, be stirred to and dissolve completely.Solution is after membrane filtration is degerming, and pipeline, merging filtrate and the washing liquid of ampicillin process during mixed liquid washing and filtering with 260ml dichloromethane and 16ml triethylamine.
In 609ml methyl acetate, add 140 grams of Sodium isooctanoate., be stirred to and dissolve completely.Solution after membrane filtration is degerming, and by pipeline, merging filtrate and the washing liquid of Sodium isooctanoate. process during 200ml methyl acetate washing and filtering.
Ampicillin 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, sucking 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 active carbon, 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 container, 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, sucking filtration, with washing with acetone, obtain ampicillin finished product after vacuum drying, purity is 99.93%.
By obtained ampicillin and highly purified sulbactam sodium 2:1 Homogeneous phase mixing by weight.
Embodiment 2
Add 527ml dichloromethane and 123ml triethylamine in the reactor, stir, cool to 0 DEG C, add 200 grams, ampicillin, be stirred to and dissolve completely.Solution is after membrane filtration is degerming, and pipeline, merging filtrate and the washing liquid of ampicillin process during mixed liquid washing and filtering with 260ml dichloromethane and 16ml triethylamine.
In 609ml methyl acetate, add 140 grams of Sodium isooctanoate., be stirred to and dissolve completely.Solution after membrane filtration is degerming, and by pipeline, merging filtrate and the washing liquid of Sodium isooctanoate. process during 200ml methyl acetate washing and filtering.
Ampicillin 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, sucking 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 active carbon, 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 container, 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, sucking filtration, with washing with acetone, obtain ampicillin finished product after vacuum drying, purity is 99.95%.
By obtained ampicillin and highly purified sulbactam sodium 2:1 Homogeneous phase mixing by weight.
Embodiment 3
Add 527ml dichloromethane and 123ml triethylamine in the reactor, stir, cool to 0 DEG C, add 200 grams, ampicillin, be stirred to and dissolve completely.Solution is after membrane filtration is degerming, and pipeline, merging filtrate and the washing liquid of ampicillin process during mixed liquid washing and filtering with 260ml dichloromethane and 16ml triethylamine.
In 609ml methyl acetate, add 140 grams of Sodium isooctanoate., be stirred to and dissolve completely.Solution after membrane filtration is degerming, and by pipeline, merging filtrate and the washing liquid of Sodium isooctanoate. process during 200ml methyl acetate washing and filtering.
Ampicillin 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, sucking 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 active carbon, 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 container, vibration, takes out after the freezing 8h of temperature control-10 DEG C.
By solid-liquor separation, discard the mixed solution 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, sucking filtration, with washing with acetone, obtain ampicillin finished product after vacuum drying, purity is 99.92%.
By obtained ampicillin and highly purified sulbactam sodium 2:1 Homogeneous phase mixing by weight.
Embodiment 4 (comparative example)
18.5kg Sodium isooctanoate. is dissolved in 56.5kg methyl acetate, gained solution is filtered, the place passed through with solution during methyl acetate washing and filtering, filtrate and washing liquid are merged, the liquid after merging is placed in sterilizing room gravity tank and saves backup at 4 DEG C.By 30kg ampicillin three water acid dissolve in the mixed solution of the two 2-aminopropane. of 45.522kg dehydrated alcohol and 21.381kg, to be dissolved completely after, be cooled to 2 DEG C, add active carbon, first de-carbon filters, then aseptic filtration, collects filtrate; With the place that filtrate during dehydrated alcohol washing and filtering is passed through, collect cleaning mixture; Merging filtrate and cleaning mixture, be placed in sterilizing room crystallizer by the liquid after merging and save backup at 4 DEG C.
Stir the sodium iso-octoate solution in sterilizing room gravity tank while join in crystallizer, in crystallizer, start crystallization produce, crystallization condition is: temperature 0 DEG C, stirs 80 minutes under the mixing speed of 100 revs/min; ) that 10L methyl acetate is placed on sterilizing room gravity tank through aseptic filtration is for subsequent use; The crystallization of the generation in crystallizer filtered, with the methyl acetate wash crystallization powder in sterilizing room gravity tank 2 times, filtrate and washing liquid reclaim, and the crystal after washing is drying to obtain ampicillin sodium salt.
Embodiment 5
The preparation of glucose sodium chloride potassium injection:
Configuration 1: glucose 8g, sodium chloride 0.18g, potassium chloride 0.15g, inject water to 100mL, with 0.22 μm of microporous filter membrane aseptic filtration.
Configuration 2: glucose 5g, sodium chloride 0.11g, potassium chloride 0.1g, inject water to 100mL, with 0.22 μm of microporous filter membrane aseptic filtration.
Embodiment 6
The preparation of Dextrose and Sodium Chloride Inj.:
Configuration 3: glucose 8g, sodium chloride 0.18g, inject water to 100mL, with 0.22 μm of microporous filter membrane aseptic filtration.
Configuration 4: glucose 5g, sodium chloride 0.11g, inject water to 100mL, with 0.22 μm of microporous filter membrane aseptic filtration.
Embodiment 7
The preparation of assembly packaging medicine:
The child form ampicillin and sulbactam sodium of embodiment 1-3 and the glucose sodium chloride potassium injection of embodiment 5-6 or Dextrose and Sodium Chloride Inj. are carried out assembly packaging according to 0.25g:100ml, 0.5g:100ml, 0.75g:100ml, 1.0g:100ml respectively.
Get the ampicillin that the ampicillin be made up of embodiment 1-3 and embodiment 4 traditional handicraft 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, color level, content, related substance, and with 0 month results contrast, result of the test is in table 1.
Table 1
Result shows: the ampicillin that the present invention prepares is in accelerated test, and character, solution colour, related substance etc. are without significant change, and its stability is good, significantly better than the ampicillin of comparative example.
More than describe preferred embodiment of the present invention in detail.Should be appreciated that those of ordinary skill in the art just design according to the present invention can make many modifications and variations without the need to creative work.Therefore, all technical staff in the art, all should by the determined protection domain of claims under this invention's idea on the basis of existing technology by the available technical scheme of logical analysis, reasoning, or a limited experiment.
Claims (10)
1. the low sodium carrier pharmaceutical composition of child form ampicillin and sulbactam sodium, is characterized in that, described pharmaceutical composition is ampicillin and sulbactam sodium glucose sodium chloride potassium injection or ampicillin and sulbactam sodium Dextrose and Sodium Chloride Inj.; Described ampicillin and sulbactam sodium glucose sodium chloride potassium injection comprises each component of following quality:
Ampicillin and sulbactam sodium 0.25g-1.0g;
Glucose 5-9g;
Sodium chloride 0.1-0.2g;
Potassium chloride 0.1-0.2g;
Add water to 100mL.
Described ampicillin and sulbactam sodium Dextrose and Sodium Chloride Inj. comprises each component of following quality:
Ampicillin and sulbactam sodium 0.25g-1.0g;
Glucose 5-9g;
Sodium chloride 0.1-0.2g;
Add water to 100mL.
2. child form ampicillin and sulbactam sodium as claimed in claim 1 and low sodium carrier pharmaceutical composition, it is characterized in that, described pharmaceutical composition can be packed for Combination application.
3. child form ampicillin and sulbactam sodium as claimed in claim 1 and low sodium carrier pharmaceutical composition, it is characterized in that, described ampicillin and sulbactam sodium is prepared by following steps:
(1) dichloromethane and triethylamine is added in the reactor, stir, cool to 0 DEG C, add ampicillin, 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, sucking filtration, filter cake methyl acetate washs, and vacuum drying obtains ampicillin crude product;
(2) ampicillin crude product is dissolved in purified water, adds active carbon, stir decolouring, filter;
(3) under agitation add extractant 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 extractant, solid drips acetone at 5 DEG C, low rate mixing, growing the grain after melting, and filters, washing, and vacuum drying, obtains ampicillin;
(5) by described ampicillin and highly purified sulbactam sodium 2:1 Homogeneous phase mixing by weight.
4. child form ampicillin and sulbactam sodium as claimed in claim 3 and low sodium carrier pharmaceutical composition, it is characterized in that, in described step (1), the weight ratio of ampicillin and dichloromethane is 1:3.5, the weight of triethylamine is 45% of ampicillin, the weight ratio of methyl acetate and Sodium isooctanoate. is 4:1, and the weight of Sodium isooctanoate. is 70% of ampicillin.
5. child form ampicillin and sulbactam sodium as claimed in claim 3 and low sodium carrier pharmaceutical composition, it is characterized in that, in described step (1), sodium iso-octoate solution first time addition 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.
6. child form ampicillin and sulbactam sodium as claimed in claim 3 and low sodium carrier pharmaceutical composition, it is characterized in that, in described step (2), ampicillin solution concentration is 0.1 ~ 0.3g/ml, and activated carbon dosage is 3 ~ 10% of ampicillin crude product.
7. child form ampicillin and sulbactam sodium as claimed in claim 3 and low sodium carrier pharmaceutical composition, is characterized in that, in described step (3), extractant is several mixture of ethyl acetate, chloroform, ether or more.
8. child form ampicillin and sulbactam sodium as claimed in claim 3 and low sodium carrier pharmaceutical composition, is characterized in that, in described step (3), the volume ratio of extractant and the middle purified water of step (2) is 1:100 ~ 200.
9. child form ampicillin and sulbactam sodium as claimed in claim 3 and low sodium carrier pharmaceutical composition, is characterized in that, in described step (3), temperature control cryogenic temperature is-20 ~-10 DEG C, and cooling time is 2 ~ 8 hours.
10. child form ampicillin and sulbactam sodium as claimed in claim 3 and low sodium carrier pharmaceutical composition, 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.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107007554A (en) * | 2017-06-01 | 2017-08-04 | 四川制药制剂有限公司 | Ampicillin Sodium For Injection sulbactam production technology |
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| CN1751751A (en) * | 2005-09-07 | 2006-03-29 | 华北制药集团有限责任公司 | Immediate dispensing infusion |
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| 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 |
| 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 |
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| CN107007554A (en) * | 2017-06-01 | 2017-08-04 | 四川制药制剂有限公司 | Ampicillin Sodium For Injection sulbactam production technology |
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Application publication date: 20150923 |
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