CN105267141A - Ceftezole sodium compound entity for children and preparation therefor - Google Patents
Ceftezole sodium compound entity for children and preparation therefor Download PDFInfo
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- CN105267141A CN105267141A CN201510280293.8A CN201510280293A CN105267141A CN 105267141 A CN105267141 A CN 105267141A CN 201510280293 A CN201510280293 A CN 201510280293A CN 105267141 A CN105267141 A CN 105267141A
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- sodium
- cefobutazine
- pharmaceutical composition
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Abstract
The invention relates to a child-type ceftezole sodium medicine composition, namely, a medicine combination preparation of ceftezole sodium and a low-sodium carrier fluid and especially provides a combination application package. The combination application package comprises ceftezole sodium for injection and a low-sodium carrier fluid. The low-sodium carrier fluid contains a glucose and sodium chloride injection (15-200:1), a glucose and sodium chloride potassium chloride injection (15-200:1:0-1) and the like. Clinic application steps are simplified through compatibility and mixing of ceftezole sodium and the low-sodium carrier fluid, clinic risks caused by that child kidneys have not been mature and have no capacity to metabolize excess sodium in blood are reduced, and clinic application quality and safety of medication for children are raised.
Description
Technical field
The present invention relates to a kind of children's with Cefobutazine sodium compound entity and preparation thereof, belong to medicinal chemistry art.
Background technology
Cefobutazine sodium, chemical name is: (6R, 7R)-3-[(1,3,4-thiadiazoles-2-base) sulphomethyl]-8-oxo-7-[2-(1H-TETRAZOLE-1-base) acetylamino]-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2 sodium formate, Chinese another name: Ceftezole Sodium.
Cefobutazine sodium is semisynthetic cephalosporins derivatives, and its mechanism of action plays antibacterial activity by the synthesis of anti-bacteria cell wall.Cefobutazine sodium has antibacterial activity to following antibacterial: 1, aerobic gram positive bacteria: staphylococcus aureus, streptococcus pneumoniae, micrococcus scarlatinae.2, aerobic gram-negative bacteria: escherichia coli, klebsiella pneumoniae, Bacillus proteus.
Powder injection formulation prepared by the monohydrate raw material direct packaging that the listing kind of current cefobutazine sodium is mostly cefobutazine sodium.Very strong draw moist because cefobutazine sodium has, in subpackage preparation process, there is very large difficulty, mobility is very poor, and requires very high to ambient humidity, and operating process is complicated, not easy to operate.Meanwhile, because cefobutazine sodium is deposited in process, particularly under the condition of high temperature (> 50 DEG C), often there is degraded and polyreaction, thus causing active constituents of medicine content to reduce, color and luster is strengthened, and polymeric impurities content raises.In addition, expired cefobutazine sodium due to the resting period long, be also usually active constituents of medicine content reduce, darken, polymer content raise.And during polymer content height, easily make human body produce anaphylaxis.In order to ensure human administration's safety, for this kind of impurities left or the high cefobutazine sodium of impurity content, be necessary to research and solve purity problem further, obtain the cefobutazine sodium that purity is high.
In CN102286001A, ceftezole acid crude is joined containing in the aqueous solution of the sodium bicarbonate of equimolar amounts and isopropyl alcohol, stir, boil off partial solvent, stirring and crystallizing, filter and obtain cefobutazine sodium.
CN102219785A, on the basis of ceftezole acid, adopts sodium acetate salify, adds dehydrated alcohol crystallize.
Cefobutazine sodium crude product and distilled water mix to entirely molten by CN102010430A, add active carbon and stir, and filter; In filtrate, slowly add aseptic acetone, continue to stir, the white precipitate of generation is drained, filtered; The aseptic washing with acetone of filter cake, and dry at normal temperatures, obtained aseptic cefobutazine sodium solid.
Above method and traditional handicraft, effectively can not solve cefobutazine sodium polymer and the problem such as other impurity content and crystal formation control.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 cefobutazine sodium is current problem demanding prompt solution, has great Social benefit and economic benefit.
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 cefobutazine sodium is in use possible, invent and a kind ofly can meet the child form cefobutazine sodium of child's stage physiological characteristics and low sodium carrier pharmaceutical composition, namely the carrier transfusion of low sodium is packed with cefobutazine 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 cefobutazine 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 ceftezole sodium pharmaceutical composition and cefobutazine sodium and low sodium carrier are infused, especially Combination application packaging, with a kind of cefobutazine sodium preparation method, it can solve above-mentioned shortcoming of the prior art.
The present invention is by the following technical solutions:
A kind of child form cefobutazine sodium and low sodium carrier pharmaceutical composition are cefobutazine sodium glucose sodium chloride potassium injection or cefobutazine sodium Dextrose and Sodium Chloride Inj..
Preferably, this cefobutazine sodium glucose sodium chloride potassium injection comprises each component of following quality:
Cefobutazine sodium 0.25-1.0g;
Glucose 5-9g;
Sodium chloride 0.1-0.2g;
Potassium chloride 0.1-0.2g;
Add water to 100mL.
Preferably, this cefobutazine sodium Dextrose and Sodium Chloride Inj. comprises each component of following quality:
Cefobutazine sodium 0.25-1.0g;
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 cefobutazine sodium is prepared by following steps:
(1) by ceftezole acid crude, etc. mole sodium bicarbonate water-soluble, under nitrogen protection, add active carbon, stir decolouring, filter;
(2) add extractant in filtrate under stirring, be transferred to and be full of in pressure vessel, after removing bubble, sealing is vibrated, the freezing rear taking-up of temperature control;
(3) remove organic facies, solid at 5-15 DEG C, slowly drips ethanol in ultrasonic field, low rate mixing, growing the grain after melting, and filter, washing with alcohol, vacuum drying, obtains cefobutazine sodium finished product.
Preferably, in step (1), ceftezole solution concentration is no more than 0.3g/ml.
Preferably, extractant is several mixing of ethyl acetate, chloroform, ether or more.
Preferably, in step (2), the volume ratio of described extractant and the middle water of step (1) is 1:100 ~ 200.
Preferably, temperature control cryogenic temperature is greater than the fusing point of extractant.
Preferably, in step (2), take out after being refrigerated to aqueous portion or fully charge.
Technique scheme has following beneficial effect: 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 cefobutazine sodium in extractant, reduce the impurity content in finished product; In the process of simultaneously water condensation Cheng Bing, because organic impurities is extruded in ice, further increase extraction efficiency, reduce impurity content; By the obtained cefobutazine sodium of this preparation method relative to traditional handicraft, have that impurity is few, purity advantages of higher.Meanwhile, have employed the carrier flow of infusate assembly packaging of cefobutazine 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
(1) take ceftezole acid crude 100g, sodium bicarbonate 20g, add water 1000ml, and stirring at room temperature, to all dissolving, adds 10g active carbon under nitrogen protection, stirs decolouring, filters;
(2) in above-mentioned filtrate, add 10ml ethyl acetate under stirring, be transferred in 1000ml pressure vessel, guarantee to be full of and bubble removal, sealed container, vibration, takes out after the freezing 8h of temperature control-18 DEG C;
(3) remove organic facies, after ice-out, be transferred to crystallizer, at 5-15 DEG C, within in ultrasonic field about 1 hour, drip 5000ml ethanol, low rate mixing 30min, continue growing the grain 1h, sucking filtration, with washing with alcohol, vacuum drying, aseptic subpackaged, obtain cefobutazine sodium finished product.Maximum list assorted 0.23%, always mix 0.33%, polymer content is 0.01%.
Embodiment 2
(1) take ceftezole acid crude 100g, sodium bicarbonate 20g, add water 1000ml, and stirring at room temperature, to all dissolving, adds 10g active carbon under nitrogen protection, stirs decolouring, filters;
(2) in above-mentioned filtrate, add 10ml ether under stirring, be transferred in 1000ml pressure vessel, guarantee to be full of and bubble removal, sealed container, vibration, takes out after the freezing 8h of temperature control-18 DEG C;
(3) remove organic facies, after ice-out, be transferred to crystallizer, at 5-15 DEG C, within in ultrasonic field about 1 hour, drip 5000ml ethanol, low rate mixing 30min, continue growing the grain 1h, sucking filtration, with washing with alcohol, vacuum drying, aseptic subpackaged, obtain cefobutazine sodium finished product.Maximum list assorted 0.25%, always mix 0.40%, polymer content is 0.01%.
Embodiment 3
(1) take ceftezole acid crude 100g, sodium bicarbonate 20g, add water 1000ml, and stirring at room temperature, to all dissolving, adds 10g active carbon under nitrogen protection, stirs decolouring, filters;
(2) in above-mentioned filtrate, add 5ml ethyl acetate under stirring, be transferred in 1000ml pressure vessel, guarantee to be full of and bubble removal, sealed container, vibration, takes out after the freezing 3h of temperature control-18 DEG C;
(3) remove organic facies, after ice-out, be transferred to crystallizer, at 5-15 DEG C, within in ultrasonic field about 1 hour, drip 5000ml ethanol, low rate mixing 30min, continue growing the grain 1h, sucking filtration, with washing with alcohol, vacuum drying, aseptic subpackaged, obtain cefobutazine sodium finished product.Maximum list assorted 0.31%, always mix 0.53%, polymer content is 0.01%.
Embodiment 4 (comparative example)
Traditionally, take ceftezole acid crude 100g, sodium bicarbonate 20g, add water 1000ml, and stirring at room temperature, to all dissolving, adds 10g active carbon, stirs decolouring, filters; Be transferred to crystallizer, drip 5000ml ethanol, low rate mixing 30min, continue growing the grain 1h, sucking filtration, with washing with alcohol, vacuum drying, aseptic subpackaged, obtain cefobutazine sodium finished product.Maximum list assorted 0.68%, always mix 1.73%, polymer content is 0.10%.
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 cefobutazine 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.
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. child form cefobutazine sodium and a low sodium carrier pharmaceutical composition, is characterized in that, described pharmaceutical composition is cefobutazine sodium glucose sodium chloride potassium injection or cefobutazine sodium Dextrose and Sodium Chloride Inj..
2. child form cefobutazine sodium as claimed in claim 1 and low sodium carrier pharmaceutical composition, it is characterized in that, described cefobutazine sodium glucose sodium chloride potassium injection comprises each component of following quality:
Cefobutazine sodium 0.25-1.0g;
Glucose 5-9g;
Sodium chloride 0.1-0.2g;
Potassium chloride 0.1-0.2g;
Add water to 100mL.
3. child form cefobutazine sodium as claimed in claim 1 and low sodium carrier pharmaceutical composition, it is characterized in that, described cefobutazine sodium Dextrose and Sodium Chloride Inj. comprises each component of following quality:
Cefobutazine sodium 0.25-1.0g;
Glucose 5-9g;
Sodium chloride 0.1-0.2g;
Add water to 100mL.
4. the child form cefobutazine sodium as described in claim 1 or 2 or 3 and low sodium carrier pharmaceutical composition, is characterized in that, described pharmaceutical composition can be packed for Combination application.
5. child form cefobutazine sodium as claimed in claim 1 and low sodium carrier pharmaceutical composition, it is characterized in that, described cefobutazine sodium is prepared by following steps:
(1) by ceftezole acid crude, etc. mole sodium bicarbonate water-soluble, under nitrogen protection, add active carbon, stir decolouring, filter;
(2) add extractant in filtrate under stirring, be transferred to and be full of in pressure vessel, after removing bubble, sealing is vibrated, the freezing rear taking-up of temperature control;
(3) remove organic facies, solid at 5-15 DEG C, slowly drips ethanol in ultrasonic field, low rate mixing, growing the grain after melting, and filter, washing with alcohol, vacuum drying, obtains cefobutazine sodium finished product.
6. child form cefobutazine sodium as claimed in claim 5 and low sodium carrier pharmaceutical composition, it is characterized in that, in described step (1), ceftezole solution concentration is no more than 0.3g/ml.
7. child form cefobutazine sodium as claimed in claim 5 and low sodium carrier pharmaceutical composition, it is characterized in that, described extractant is several mixing of ethyl acetate, chloroform, ether or more.
8. child form cefobutazine sodium as claimed in claim 5 and low sodium carrier pharmaceutical composition, is characterized in that, in described step (2), the volume ratio of described extractant and the middle water of step (1) is 1:100 ~ 200.
9. child form cefobutazine sodium as claimed in claim 5 and low sodium carrier pharmaceutical composition, it is characterized in that, described temperature control cryogenic temperature is greater than the fusing point of extractant.
10. child form cefobutazine sodium as claimed in claim 5 and low sodium carrier pharmaceutical composition, is characterized in that, in described step (2), take out after being refrigerated to aqueous portion or fully charge.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510280293.8A CN105267141A (en) | 2015-05-28 | 2015-05-28 | Ceftezole sodium compound entity for children and preparation therefor |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510280293.8A CN105267141A (en) | 2015-05-28 | 2015-05-28 | Ceftezole sodium compound entity for children and preparation therefor |
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| CN105267141A true CN105267141A (en) | 2016-01-27 |
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| CN201510280293.8A Pending CN105267141A (en) | 2015-05-28 | 2015-05-28 | Ceftezole sodium compound entity for children and preparation therefor |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1751751A (en) * | 2005-09-07 | 2006-03-29 | 华北制药集团有限责任公司 | Immediate dispensing infusion |
| 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 |
| CN102775426A (en) * | 2012-08-10 | 2012-11-14 | 天津新丰制药有限公司 | Crystallization method of ceftezole sodium |
-
2015
- 2015-05-28 CN CN201510280293.8A patent/CN105267141A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1751751A (en) * | 2005-09-07 | 2006-03-29 | 华北制药集团有限责任公司 | Immediate dispensing infusion |
| 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 |
| CN102775426A (en) * | 2012-08-10 | 2012-11-14 | 天津新丰制药有限公司 | Crystallization method of ceftezole sodium |
Non-Patent Citations (2)
| Title |
|---|
| 国家药典委员会: "《中华人民共和国药典2010年版第一增补本》", 31 August 2012 * |
| 迟延青等: "《最新临床用药必备》", 31 January 2011 * |
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Application publication date: 20160127 |
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