CN105055423A - Medicine ceftezole sodium composition for curing infectious diseases - Google Patents
Medicine ceftezole sodium composition for curing infectious diseases Download PDFInfo
- Publication number
- CN105055423A CN105055423A CN201510587405.4A CN201510587405A CN105055423A CN 105055423 A CN105055423 A CN 105055423A CN 201510587405 A CN201510587405 A CN 201510587405A CN 105055423 A CN105055423 A CN 105055423A
- Authority
- CN
- China
- Prior art keywords
- sodium
- ceftezole
- cefobutazine
- medicine
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a medicine ceftezole sodium composition for curing infectious diseases, belonging to the technical field of medicines. The composition is prepared from ceftezole sodium and anhydrous sodium carbonate; the ceftezole sodium is a crystal, and an X-ray powder diffraction pattern obtained by Cu-Kalpha ray measurement is shown as picture 1. The new crystal form of the ceftezole sodium provided by the invention is different from crystal form structures in the prior art, by means of experimental verification, the new crystal form compound is surprisedly found to be high in purity, good in mobility and stability, low in polymer content, free of hygroscopicity and safe and reliable in clinic application, and a powder-injection prepared by using the new crystal form compound is good in stability, good in stability after being matched with a solvent, extremely low in insoluble particle content and very suitable for clinic application.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine ceftezole composition of sodium for the treatment of infectious disease.
Background technology
Cefobutazine sodium is first generation cephalosporin for injections, is developed by Japanese Teng Ze company, and first in state's listings such as Japan, Korea S, Italy.Containing unstable beta-lactam nucleus in the structure of cefobutazine sodium, easy generation hydrolysis and rearrangement reaction, cause structural damage and lose antibacterial activity, some catabolite may produce anaphylaxis, and therefore the stability of this kind of antibiotic in transfusion should cause extensive attention.Meanwhile, because its basic structure is the same with antibiotic in the many semisynthetic beta-lactam gone on the market, also can forms high molecular polymer, also can cause type Ⅰ hypersensitivity reaction in Clinical practice, very harmful to patient.Meanwhile, cefobutazine sodium very easily draws wet, has very adverse influence to its stability.Prior art improves its stability from aspects such as raising content, reduction impurity mostly.
Research proves, the anaphylactogen causing beta-lactam antibiotic type Ⅰ hypersensitivity reaction is relevant with the high molecular polymer content wherein existed.Reduce the high molecular polymer content existed in cefobutazine sodium crude drug, improve stability, make it can ensure the lower effective way being the reaction of reduction anaphylactic shock and occurring of the content of its high molecular polymer existed in long term storage.Therefore, be necessary to provide the Cefobutazine sodium compound that a kind of high molecular polymer content is low, performance is more superior.
The present invention, through large quantifier elimination, obtains a kind of crystal compound being different from prior art, and the purity of cefobutazine sodium crystalline compounds provided by the invention is high, good fluidity, not easily moisture absorption, good stability, and polymer content is low, and clinical practice is safe and reliable.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of medicine ceftezole composition of sodium for the treatment of infectious disease.
In order to complete object of the present invention, the technical scheme of employing is:
Treat a medicine ceftezole composition of sodium for infectious disease, consisting of of described compositions: cefobutazine sodium 1 weight portion, natrium carbonicum calcinatum 0.001-0.003 weight portion; Described cefobutazine sodium is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
Preferably, consisting of of described compositions: cefobutazine sodium 1 weight portion, natrium carbonicum calcinatum 0.0015-0.0025 weight portion.
Preferably, consisting of of described compositions: cefobutazine sodium 1 weight portion, natrium carbonicum calcinatum 0.002 weight portion.
Preferably, the dosage form of described compositions is injection, and the preparation method of described injection comprises the following steps:
(1) take ceftezole sodium crystal and natrium carbonicum calcinatum in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
The preparation method of the ceftezole sodium crystal in described compositions comprises the following steps:
(1) ground by cefobutazine sodium crude product, cross 60 mesh sieves, then joining volume is in the deionized water of 6 times of cefobutazine sodium weight, and 130 revs/min are stirred 10 minutes;
Add the methanol that volume is 4 times of cefobutazine sodium weight under (2) 90 revs/min of stirrings, be warming up to 30 DEG C simultaneously;
(3) after solution adds, leave standstill 3 hours, the volume dripping 0 DEG C under 150 revs/min of conditions stirred is 8 times of ethanol of cefobutazine sodium weight, the mixed solution of chloroform, and the volume ratio of ethanol, chloroform is at the uniform velocity dropwise in 3:1,2h;
(4) be cooled to-5 DEG C after being added dropwise to complete, continue to stir 2h under the stir speed (S.S.) of 80 revs/min, leave standstill 1h crystallize out, filter, washing, vacuum drying obtains ceftezole sodium crystal.
The polymorphism of solid chemical is the natural phenomena that a kind of general material exists, this phenomenon refers to that a kind of solid chemical can exist 2 kinds or two or more crystal form state, be also called the polymorphic state of material, the polymorphic state of material is also referred to as " allomorphism " phenomenon.Although its chemical nature of allomorphous solid matter is identical, its physicochemical property may be different.For " allomorphism medicine " that physicochemical property is different, also can show the curative effect of different disease preventing and treating clinically, directly affect application and the clinical effectiveness of medicine.
Cefobutazine sodium is Beta-lactam medicine, the easy open loop of its monoamides ring, form impurity and easily self-polymerization occur after open loop, form high molecular polymer, thus reduction medicament contg, cause drug titers to reduce, the sterilization of cefobutazine sodium and fungistatic effect are reduced, and high polymer can cause endogenous anaphylaxis.The good stability of the Cefobutazine sodium compound that the present invention prepares, not easily open loop is decomposed, its polymer content trace.
Cefobutazine sodium has and draws moist, can cause the change of the physicochemical properties such as the decline of caking, mobility, deliquescence, crystal formation change, thus affect the interior qualities such as product stability, effectiveness, safety after moisture absorption.And according to the literature, many antibiotic are stablized in the dry state, but will decompose after making moist.Therefore, hygroscopicity has very important impact for the stability of cefobutazine sodium.Therefore, if can reduce the hygroscopicity of cefobutazine sodium, then the stability for cefobutazine sodium has very important meaning.Meanwhile, bibulous medicine needs strictly to control the relative humidity between subpackage in formulation manufacturing processes, is no more than critical relative humidity, thus ensures product quality and stability.If not easily moisture absorption, then the production of convenient preparation, ensures stability simultaneously.
A kind of germ killing drugs Cefobutazine sodium compound of the present invention, the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.By to its hygroscopic research, the discovery that inventor is pleasantly surprised, its hygroscopicity of compound of the present invention is significantly less than existing crystalline compounds.Thus illustrate that cefobutazine sodium crystalline compounds of the present invention is more stable, and more adapt to the preparation of preparation.
The purity of cefobutazine sodium crystalline compounds of the present invention can reach 99.8%, and its structure is confirmed through proton nmr spectra.The preparation method of cefobutazine sodium crystalline compounds of the present invention is simple, and purity is high, and yield is high, most suitable large-scale industrial production.
The injectable powder that cefobutazine sodium crystalline compounds of the present invention is obtained, good stability, good with solvent compatibility rear stability, particulate matter content is extremely low, is very suitable for clinical practice.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the ceftezole sodium crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
Detailed description of the invention
Below by specific embodiment, summary of the invention of the present invention is described in further detail, but does not therefore limit content of the present invention.
embodiment 1:the preparation of ceftezole sodium crystal
(1) ground by cefobutazine sodium crude product, cross 60 mesh sieves, then joining volume is in the deionized water of 6 times of cefobutazine sodium weight, and 130 revs/min are stirred 10 minutes;
Add the methanol that volume is 4 times of cefobutazine sodium weight under (2) 90 revs/min of stirrings, be warming up to 30 DEG C simultaneously;
(3) after solution adds, leave standstill 3 hours, 150 revs/min of volumes stirring lower dropping 0 DEG C are 8 times of ethanol of cefobutazine sodium weight, the mixed solution of chloroform, and the volume ratio of ethanol, chloroform is 3:1, at the uniform velocity dropwises in 2h;
(4) be cooled to-5 DEG C after being added dropwise to complete, continue to stir 2h under the stir speed (S.S.) of 80 revs/min, leave standstill 1h crystallize out, filter, washing, vacuum drying obtains ceftezole sodium crystal.
As shown in Figure 1, its purity of high-performance liquid chromatogram determination is 99.8% to the X-ray powder diffraction pattern that the ceftezole sodium crystal prepared uses the measurement of Cu-K alpha ray to obtain.
embodiment 2:the preparation of ceftezole composition of sodium
Consist of: ceftezole sodium crystal 1 weight portion prepared by the present invention, natrium carbonicum calcinatum 0.001 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and natrium carbonicum calcinatum in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 3:the preparation of ceftezole composition of sodium
Consist of: ceftezole sodium crystal 1 weight portion prepared by the present invention, natrium carbonicum calcinatum 0.0015 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and natrium carbonicum calcinatum in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 4:the preparation of ceftezole composition of sodium
Consist of: ceftezole sodium crystal 1 weight portion prepared by the present invention, natrium carbonicum calcinatum 0.002 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and natrium carbonicum calcinatum in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 5:the preparation of ceftezole composition of sodium
Consist of: ceftezole sodium crystal 1 weight portion prepared by the present invention, natrium carbonicum calcinatum 0.0025 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and natrium carbonicum calcinatum in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
embodiment 6:the preparation of ceftezole composition of sodium
Consist of: ceftezole sodium crystal 1 weight portion prepared by the present invention, natrium carbonicum calcinatum 0.003 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and natrium carbonicum calcinatum in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
experimental example 1:accelerated test
Example 1 and commercially available ceftezole sodium raw materials, simulation listing packaging, puts in sealing clean container, in 25 DEG C ± 2 DEG C, place 6 months under the condition of humidity 60% ± 5%, at duration of test respectively at 1,2,3,6 sampling at the end of month once, each stability high spot reviews project is tested.The results are shown in Table shown in 1.
Table 1 Acceleration study result
experimental example 2:wettability test
1 instrument
PL203 electronic balance, LRH-250-S constant temperature and humidity incubator, HH-400SD testing chamber for medicine stability;
2 methods
Get the glass desicator (for ensureing that saline solution is saturated, excessive salt should be had bottom exsiccator to exist) that bottom fills salt supersaturated solution, the built-in weighing botle of exsiccator, places 48h to constant humidity in calorstat.Sample thief is about 2g, puts in weighing botle, accurately weighed, bottle cap is opened, puts into exsiccator top, put in 25 DEG C of constant temperature and humidity incubators or 20 DEG C of stability test casees by different temperatures requirement and preserve, operation repetitive 3 parts, weighs respectively at different time, calculates the hydroscopicity of different time.
Computing formula: hydroscopicity=(medicated powder weight after moisture absorption-moisture absorption prodrug grain weight amount)/moisture absorption prodrug grain weight amount × 100%.Result is as table 2:
Table 2 hygroscopicity test results
According to above-mentioned experiment, the hygroscopicity of cefobutazine sodium crystalline compounds prepared by the present invention is low, good stability.
experimental example 3:mobility is tested
The mobility of this experimental example to the cefobutazine sodium crystalline compounds of the embodiment of the present invention 1 detects, adopt fixed funnel method, funnel is placed in the suitable height on graph paper, cefobutazine sodium crystalline compounds is freely flowed down from bell mouth, until the cone top formed contacts with bell mouth, measure hypotenuse and the horizontal angle (θ angle of repose) of cefobutazine sodium crystalline compounds accumulation horizon.Experimental result is as shown in table 3.
Table 3 mobility experimental result
From the interpretation of table 3, the mobility of the cefobutazine sodium crystalline compounds that the embodiment of the present invention 1 prepares is fine.
Claims (5)
1. treat a medicine ceftezole composition of sodium for infectious disease, it is characterized in that: described compositions consist of cefobutazine sodium 1 weight portion, natrium carbonicum calcinatum 0.001-0.003 weight portion; Described cefobutazine sodium is crystal, and the X-ray powder diffraction pattern that the measurement of use Cu-K alpha ray obtains as shown in Figure 1.
2. the medicine ceftezole composition of sodium for the treatment of infectious disease according to claim 1, is characterized in that: described compositions consist of cefobutazine sodium 1 weight portion, natrium carbonicum calcinatum 0.0015-0.0025 weight portion.
3. the medicine ceftezole composition of sodium for the treatment of infectious disease according to claim 2, is characterized in that: described compositions consist of cefobutazine sodium 1 weight portion, natrium carbonicum calcinatum 0.002 weight portion.
4., according to the medicine ceftezole composition of sodium of the arbitrary described treatment infectious disease of claim 1-3, it is characterized in that, the dosage form of described compositions is injection, and the preparation method of described injection comprises the following steps:
(1) take ceftezole sodium crystal and natrium carbonicum calcinatum in proportion, fully mix;
(2) to divide in the cillin bottle after being filled to sterilizing and to jump a queue.
5. the medicine ceftezole composition of sodium for the treatment of infectious disease according to claim 1, is characterized in that, the crystal preparation method of described cefobutazine sodium is:
(1) ground by cefobutazine sodium crude product, cross 60 mesh sieves, then joining volume is in the deionized water of 6 times of cefobutazine sodium weight, and 130 revs/min are stirred 10 minutes;
Add the methanol that volume is 4 times of cefobutazine sodium weight under (2) 90 revs/min of stirrings, be warming up to 30 DEG C simultaneously;
(3) after solution adds, leave standstill 3 hours, the volume dripping 0 DEG C under 150 revs/min of conditions stirred is 8 times of ethanol of cefobutazine sodium weight, the mixed solution of chloroform, and the volume ratio of ethanol, chloroform is at the uniform velocity dropwise in 3:1,2h;
(4) be cooled to-5 DEG C after being added dropwise to complete, continue to stir 2h under the stir speed (S.S.) of 80 revs/min, leave standstill 1h crystallize out, filter, washing, vacuum drying obtains ceftezole sodium crystal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510587405.4A CN105055423A (en) | 2015-09-16 | 2015-09-16 | Medicine ceftezole sodium composition for curing infectious diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510587405.4A CN105055423A (en) | 2015-09-16 | 2015-09-16 | Medicine ceftezole sodium composition for curing infectious diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105055423A true CN105055423A (en) | 2015-11-18 |
Family
ID=54485108
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510587405.4A Withdrawn CN105055423A (en) | 2015-09-16 | 2015-09-16 | Medicine ceftezole sodium composition for curing infectious diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105055423A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109160922A (en) * | 2017-07-20 | 2019-01-08 | 海南灵康制药有限公司 | A kind of 1/2 water Cefobutazine sodium compound |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101544661A (en) * | 2009-05-12 | 2009-09-30 | 海南数尔药物研究有限公司 | Cefobutazine sodium compound and pharmaceutical composition made therefrom |
| CN102010430A (en) * | 2009-09-04 | 2011-04-13 | 江苏汉斯通药业有限公司 | Synthesis process of ceftezole sodium |
| CN102010429A (en) * | 2009-09-04 | 2011-04-13 | 江苏汉斯通药业有限公司 | Synthesis process of ceftezole |
| CN102872021A (en) * | 2012-09-25 | 2013-01-16 | 罗诚 | Medicinal composition containing ceftezole sodium compound and preparation method for medicinal composition |
-
2015
- 2015-09-16 CN CN201510587405.4A patent/CN105055423A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101544661A (en) * | 2009-05-12 | 2009-09-30 | 海南数尔药物研究有限公司 | Cefobutazine sodium compound and pharmaceutical composition made therefrom |
| CN102010430A (en) * | 2009-09-04 | 2011-04-13 | 江苏汉斯通药业有限公司 | Synthesis process of ceftezole sodium |
| CN102010429A (en) * | 2009-09-04 | 2011-04-13 | 江苏汉斯通药业有限公司 | Synthesis process of ceftezole |
| CN102872021A (en) * | 2012-09-25 | 2013-01-16 | 罗诚 | Medicinal composition containing ceftezole sodium compound and preparation method for medicinal composition |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109160922A (en) * | 2017-07-20 | 2019-01-08 | 海南灵康制药有限公司 | A kind of 1/2 water Cefobutazine sodium compound |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105193819A (en) | Medicine cefotiam hydrochloride composition for treating bacterial infection | |
| CN105055420A (en) | Medicine cefamandole nafate composition for treating bacterial infection | |
| CN105055423A (en) | Medicine ceftezole sodium composition for curing infectious diseases | |
| CN105055406A (en) | Antibacterial drug aztreonam composition | |
| CN105055419A (en) | Cefamandole nafate composition for the treatment of infectious diseases | |
| CN105168223A (en) | Anti-bacterial medicine-ceftezole sodium composition | |
| CN105078999A (en) | Anti-infective medicine of cefamandole nafate composition | |
| CN105125558A (en) | Antibacterial cefotiam hydrochloride drug composition | |
| CN103304597A (en) | Creatine phosphate sodium compound and preparation method thereof, and pharmaceutical composition of compound and preparation method of composition | |
| CN106432274A (en) | Crystalline compound of drug ceftriaxone sodium for treating surgical operation infections | |
| CN105030787A (en) | Ceftezole sodium composition serving as medicine for treating bacterial infection | |
| CN105106219A (en) | Anti-infective drug ceftezole sodium composition | |
| CN106432279A (en) | Method for preparing medicine ceftriaxone sodium crystal compound for treating surgical infection | |
| CN105085548A (en) | Pharmaceutical cefotiam composition for treating infectious diseases | |
| CN104997785A (en) | Antibacterial drug-cefamandole nafate composition | |
| CN105055323A (en) | Anti-infective aztreonam composition | |
| CN105061473A (en) | Sterilization medicine ceftezole sodium compound and preparation method thereof | |
| CN105012310A (en) | Angiectasis medicine fasudil hydrochloride composition | |
| CN105055407A (en) | Medicine aztreonam composition for curing infectious diseases | |
| CN105055442A (en) | Ranitidine hydrochloride composition for treating gastric diseases | |
| CN105001215A (en) | Aztreonam compound serving as sterilization medicine and preparation method thereof | |
| CN105125538A (en) | Medicinal aztreonam composition for treating bacterial infection | |
| CN105037392A (en) | Bactericidal medicine efamandole nafate compound and preparing method of bactericidal medicine efamandole nafate compound | |
| CN106432275A (en) | Method for preparing crystalline ceftriaxone sodium compound as drug for treating surgical infection | |
| CN105030694A (en) | Ranitidine hydrochloride composition dry suspension for treating gastric ulcer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20151118 |