CN105030787A - Ceftezole sodium composition serving as medicine for treating bacterial infection - Google Patents
Ceftezole sodium composition serving as medicine for treating bacterial infection Download PDFInfo
- Publication number
- CN105030787A CN105030787A CN201510584336.1A CN201510584336A CN105030787A CN 105030787 A CN105030787 A CN 105030787A CN 201510584336 A CN201510584336 A CN 201510584336A CN 105030787 A CN105030787 A CN 105030787A
- Authority
- CN
- China
- Prior art keywords
- sodium
- ceftezole
- medicine
- cefobutazine
- weight portion
- 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.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a ceftezole sodium composition serving as medicine for treating the bacterial infection, and belongs to the technical field of medicine. The composition is composed of ceftezole sodium and sodium dihydrogen phosphate. The ceftezole sodium is crystals, and the X-ray powder diffraction pattern measured through Cu-Kalpha rays is shown as figure 1. According to the ceftezole sodium composition, the novel crystal form of the ceftezole sodium is different from the crystal form structure in the prior art; due to experimental verification, an inventor is pleasantly surprised to find that the novel-crystal-form compound is high in purity, good in fluidity and stability, low in polymer content, not prone to absorbing moisture and safe and reliable in clinical application; powder-injections prepared through the novel-crystal-form compound are good in stability; after the powder-injections are mixed with solvents, stability is good, the content of insoluble particles is quite small, and the powder-injections are quite suitable for clinical application.
Description
Technical field
The invention belongs to medical art, relate to a kind of medicine ceftezole composition of sodium for the treatment of bacteriological infection.
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 bacteriological infection.
In order to complete object of the present invention, the technical scheme of employing is:
Treat a medicine ceftezole composition of sodium for bacteriological infection, consisting of of described compositions: cefobutazine sodium 1 weight portion, sodium dihydrogen phosphate 0.003-0.007 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, sodium dihydrogen phosphate 0.004-0.006 weight portion.
Preferably, consisting of of described compositions: cefobutazine sodium 1 weight portion, sodium dihydrogen phosphate 0.005 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 sodium dihydrogen phosphate 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) get cefobutazine sodium crude drug, add in deionized water, the volumetric usage of deionized water is 9 times of the quality of cefobutazine sodium;
(2) be stirred to whole dissolving, regulate pH to 6-9;
(3) add activated carbon decolorizing, filter, obtain settled solution;
(4) settled solution is moved in pressure vessel, the pressure in pressure vessel is controlled 1.5Mpa and stir condition under drip 0 DEG C 45% isopropanol water solution, speed of agitator controls at 25rmp, and the volumetric usage of isopropanol water solution is 3 times of the volume of deionized water;
(5) bleed off pressure after dripping, with the speed of 4 DEG C/min, solution is cooled to-5 DEG C, leave standstill 3.5h, filter, washed with diethylether, drying under reduced pressure, 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 99.9%, 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) get cefobutazine sodium crude drug, add in deionized water, the volumetric usage of deionized water is 9 times of the quality of cefobutazine sodium;
(2) be stirred to whole dissolving, regulate pH to 6-9;
(3) add activated carbon decolorizing, filter, obtain settled solution;
(4) settled solution is moved in pressure vessel, the pressure in pressure vessel is controlled 1.5Mpa and stir condition under drip 0 DEG C 45% isopropanol water solution, speed of agitator controls at 25rmp, and the volumetric usage of isopropanol water solution is 3 times of the volume of deionized water;
(5) bleed off pressure after dripping, with the speed of 4 DEG C/min, solution is cooled to-5 DEG C, leave standstill 3.5h, filter, washed with diethylether, drying under reduced pressure, obtains ceftezole sodium crystal.
As shown in Figure 1, its purity of high-performance liquid chromatogram determination is 99.9% 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, sodium dihydrogen phosphate 0.003 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and sodium dihydrogen phosphate 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, sodium dihydrogen phosphate 0.004 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and sodium dihydrogen phosphate 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, sodium dihydrogen phosphate 0.005 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and sodium dihydrogen phosphate 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, sodium dihydrogen phosphate 0.006 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and sodium dihydrogen phosphate 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, sodium dihydrogen phosphate 0.007 weight portion.
Preparation method is:
(1) take ceftezole sodium crystal and sodium dihydrogen phosphate 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 bacteriological infection, it is characterized in that: described compositions consist of cefobutazine sodium 1 weight portion, sodium dihydrogen phosphate 0.003-0.007 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 bacteriological infection according to claim 1, is characterized in that: described compositions consist of cefobutazine sodium 1 weight portion, sodium dihydrogen phosphate 0.004-0.006 weight portion.
3. the medicine ceftezole composition of sodium for the treatment of bacteriological infection according to claim 2, is characterized in that: described compositions consist of cefobutazine sodium 1 weight portion, sodium dihydrogen phosphate 0.005 weight portion.
4., according to the medicine ceftezole composition of sodium of the arbitrary described treatment bacteriological infection 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 cefobutazine sodium and sodium dihydrogen phosphate 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 bacteriological infection according to claim 1, is characterized in that, the crystal preparation method of described cefobutazine sodium is:
(1) get cefobutazine sodium crude drug, add in deionized water, the volumetric usage of deionized water is 9 times of the quality of cefobutazine sodium;
(2) be stirred to whole dissolving, regulate pH to 6-9;
(3) add activated carbon decolorizing, filter, obtain settled solution;
(4) settled solution is moved in pressure vessel, the pressure in pressure vessel is controlled 1.5Mpa and stir condition under drip 0 DEG C 45% isopropanol water solution, speed of agitator controls at 25rmp, and the volumetric usage of isopropanol water solution is 3 times of the volume of deionized water;
(5) bleed off pressure after dripping, with the speed of 4 DEG C/min, solution is cooled to-5 DEG C, leave standstill 3.5h, filter, washed with diethylether, drying under reduced pressure, obtains ceftezole sodium crystal.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510584336.1A CN105030787A (en) | 2015-09-15 | 2015-09-15 | Ceftezole sodium composition serving as medicine for treating bacterial infection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510584336.1A CN105030787A (en) | 2015-09-15 | 2015-09-15 | Ceftezole sodium composition serving as medicine for treating bacterial infection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105030787A true CN105030787A (en) | 2015-11-11 |
Family
ID=54438155
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510584336.1A Pending CN105030787A (en) | 2015-09-15 | 2015-09-15 | Ceftezole sodium composition serving as medicine for treating bacterial infection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105030787A (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286001A (en) * | 2011-08-30 | 2011-12-21 | 郑州大学 | Method for preparing ceftezole sodium |
-
2015
- 2015-09-15 CN CN201510584336.1A patent/CN105030787A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102286001A (en) * | 2011-08-30 | 2011-12-21 | 郑州大学 | Method for preparing ceftezole sodium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102659818A (en) | Hydrochloric acid cefotiam crystalline compound, preparation method thereof and medicine combination containing compound | |
| CN105193819A (en) | Medicine cefotiam hydrochloride composition for treating bacterial infection | |
| CN105055420A (en) | Medicine cefamandole nafate composition for treating bacterial infection | |
| CN102367229B (en) | Ethylenediamine diaceturate compound and pharmaceutical composition thereof | |
| CN105055406A (en) | Antibacterial drug aztreonam composition | |
| CN105055423A (en) | Medicine ceftezole sodium composition for curing infectious diseases | |
| CN105055419A (en) | Cefamandole nafate composition for the treatment of infectious diseases | |
| CN105168223A (en) | Anti-bacterial medicine-ceftezole sodium composition | |
| CN105030787A (en) | Ceftezole sodium composition serving as medicine for treating bacterial infection | |
| CN105125558A (en) | Antibacterial cefotiam hydrochloride drug composition | |
| CN105078999A (en) | Anti-infective medicine of cefamandole nafate composition | |
| CN103304597A (en) | Creatine phosphate sodium compound and preparation method thereof, and pharmaceutical composition of compound and preparation method of composition | |
| CN103450086B (en) | Ozagrel compound, preparation method and pharmaceutical composition of ozagrel compound | |
| CN106432279A (en) | Method for preparing medicine ceftriaxone sodium crystal compound for treating surgical infection | |
| CN106432274A (en) | Crystalline compound of drug ceftriaxone sodium for treating surgical operation infections | |
| CN105106219A (en) | Anti-infective drug ceftezole sodium composition | |
| CN105085548A (en) | Pharmaceutical cefotiam composition for treating infectious diseases | |
| CN104997785A (en) | Antibacterial drug-cefamandole nafate composition | |
| CN105001215A (en) | Aztreonam compound serving as sterilization medicine and preparation method thereof | |
| 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 | |
| CN105125538A (en) | Medicinal aztreonam composition for treating bacterial infection | |
| CN105055442A (en) | Ranitidine hydrochloride composition for treating gastric diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20170608 Address after: 050050 No. 188 worker peasant Road, Hebei, Shijiazhuang Applicant after: Zhongnuo Pharmaceutical (Shijiazhuang) Co., Ltd., Shiyao Group Address before: Emei Huangdao District 266555 in Shandong province Qingdao city Qingdao Road No. 396 Optics Valley Software Park 1.5 District twenty-seventh building second layer Applicant before: QINGDAO HUAZHICAO MEDICAL TECHNOLOGY CO., LTD. |
|
| TA01 | Transfer of patent application right | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20151111 |
|
| RJ01 | Rejection of invention patent application after publication |