CN104721190B - Ceftezole sodium injection and preparation method thereof - Google Patents
Ceftezole sodium injection and preparation method thereof Download PDFInfo
- Publication number
- CN104721190B CN104721190B CN201510138069.5A CN201510138069A CN104721190B CN 104721190 B CN104721190 B CN 104721190B CN 201510138069 A CN201510138069 A CN 201510138069A CN 104721190 B CN104721190 B CN 104721190B
- Authority
- CN
- China
- Prior art keywords
- injection
- sodium
- water
- minutes
- add
- 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.)
- Expired - Fee Related
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention relates to a ceftezole sodium injection, which is prepared from the following raw materials by weight: 42g of ceftezole sodium, 4.3g of citric acid, 8.5g of vitamin B1, 48g of polysorbate 40 and 2000 ml of water for injection, wherein the pH is regulated to be 6.4-6.5.
Description
Technical field
The present invention relates to ceftezole sodium injection and preparation method thereof.
Background technology
Cefobutazine sodium, calls Ceftezole Sodium, and its chemical name is: (6R, 7R)-3-[(1,3,4-thiadiazoles-2-base) sulfur generation
Methyl]-8-oxo-7-[2-(1H-TETRAZOLE-1-base) acetylamino]-5-thia-1-azabicyclo [4.2.0] oct-2-ene-2 first
Acid sodium, English another name: 5-Thia-1-azabicyclo [4,2,0] oct-2-ene-2-carboxylic sodium or
Sodium (6S, 7R)-8-oxo-7-[(1H-tetrazol-1-ylacetyl) amino]-3-[(1,3,4-thiadiazol-2-
ylsulf anyl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate.This product is
White to light yellow crystalline powder, odorless, have draw moist.Cefobutazine sodium is semisynthetic cephalosporins derivatives, and it is made
It is by suppressing the synthesis of bacteria cell wall to play antibacterial activity by mechanism.Cefobutazine sodium has antibacterial work to following antibacterial
Property: aerobic gram positive bacteria: staphylococcus aureus, streptococcus pneumoniae, micrococcus scarlatinae；Aerobic gram-negative bacteria:
Escherichia coli, klebsiella pneumoniae, Bacillus proteus.Indication is septicemia, pneumonia, bronchitis, bronchiectasis (sense
During dye), the secondary infection of chronic respiratory system diseases, pulmonary abscess, peritonitis, pyelonephritis, cystitis, urethritis.
Cefobutazine sodium, owing to having strong hygroscopicity, exposes and the most easily assembles in bulk, be prepared as injection easy
Produce precipitation.Existing ceftezole sodium injection easily becomes turbid because of temperature reason, and needing in use to heat makes it clarify
After can use, and dissolve after use the most immediately.
Summary of the invention
Present inventor chances on the specific injection adjuvant of selection, it is possible to significantly improve ceftezole sodium injection
The precipitation produced, improves the stability of ceftezole sodium injection.
The present invention provides a kind of ceftezole sodium injection, and wherein active component is cefobutazine sodium.
The present invention provides a kind of ceftezole sodium injection, including cefobutazine sodium and adjuvant.
The present invention provides a kind of ceftezole sodium injection, and it is made up of following raw material: cefobutazine sodium, citric acid, dimension
Raw element B1, polysorbate 40 and water for injection.
The present invention provides a kind of ceftezole sodium injection, and it is made up of following raw material: 42g cefobutazine sodium, 4.3g Chinese holly
Rafter acid, 8.5g vitamin B1,48g polysorbate 40,2000ml water for injection；Adjust pH to 6.4～6.5.
The present invention provides a kind of stable ceftezole sodium injection and preparation method thereof, described ceftezole sodium injection
Adjuvant is less, good stability, and Clinical practice safety is higher.
Present invention provide the technical scheme that ceftezole sodium injection, be made up of following raw material: 42g cefobutazine sodium,
4.3g citric acid, 8.5g vitamin B1,48g polysorbate 40,2000ml water for injection；Adjust pH to 6.4～6.5.
Wherein citric acid and vitamin B1 also play the effect of antioxidant while playing cosolvent.
Present invention also offers the preparation method of above-mentioned ceftezole sodium injection:
1, taking citric acid and the vitamin B1 of recipe quantity, add the water for injection of 50% amount, be heated to 50～55 DEG C, stirring makes
It dissolves, and the cefobutazine sodium taking recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, take the polysorbate 40 of recipe quantity, add the water for injection of 40% amount, stir 15 minutes, with hydrochloric acid (preferably 1mol/
The hydrochloric acid of L) adjust PH to 3.7～4.0.
3,1,2 solution are merged, adjust PH to 6.4～6.5 with PH regulator (sodium hydroxide solution of preferably 1mol/L), add
Water for injection, to full dose, the needle-use activated carbon adding 0.15%, stirs 25 minutes, filters decarburization, intermediate inspection, qualified rear use
0.22 μm membrane filtration is degerming.
4, pour in the ampoule bottle of 2ml respectively by specification, inflated with nitrogen, sealing by fusing, 121 DEG C of moist heat sterilizations 15 minutes, inspection is closed
After lattice, packaging.
Inventor surprisinglys found that, uses the combination of the citric acid of specified quantitative, vitamin B1 and polysorbate 40 to be prepared into
The ceftezole sodium injection stability arrived is high, and relevant content of material is few.Further, the ceftezole sodium injection adjuvant of the present invention
Less, good stability, Clinical practice safety is higher.
Detailed description of the invention
Tests below further illustrates the present invention:
Further research is it has been surprisingly found that the citric acid of specified quantitative and vitamin B1 and combining of polysorbate 40 make
Beyond thought remarkable result is served with to the quality stability improving cefobutazine sodium.
Embodiment 1:
Cefobutazine sodium: 42g
Citric acid: 4.3g
Vitamin B1: 8.5g
Polysorbate 40: 48g
PH regulator: appropriate
Water for injection: 2000ml
Technique:
1, taking citric acid and the vitamin B1 of recipe quantity, add 50% water for injection, be heated to 50～55 DEG C, stirring makes it molten
Solving, the cefobutazine sodium taking recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving.
2, take the polysorbate 40 of recipe quantity, add 40% water for injection, stir 15 minutes, with hydrochloric acid adjust pH to 3.7～
4.0。
3,1,2 solution are merged, adjust pH to 6.4～6.5 by pH adjusting agent (sodium hydroxide solution), inject water to complete
Amount, the needle-use activated carbon adding 0.15%, stir 25 minutes, filtration decarburization, intermediate inspection, qualified rear with 0.22 μm membrane filtration
Degerming, pour in the ampoule bottle of 2ml respectively by specification, inflated with nitrogen, sealing by fusing, 121 DEG C of moist heat sterilizations 15 minutes, after the assay was approved,
Packaging.
Comparative examples 1:
Cefobutazine sodium: 42g
Vitamin B1: 8.5g
Polysorbate 40: 48g
PH regulator: appropriate
Water for injection: 2000ml
Preparation method is with embodiment 1.
Comparative examples 2:
Cefobutazine sodium: 42g
Citric acid: 4.3g
Polysorbate 40: 48g
PH regulator: appropriate
Water for injection: 2000ml
Preparation method is with embodiment 1.
Comparative examples 3:
Cefobutazine sodium: 42g
Citric acid: 4.3g
Vitamin B1: 8.5g
PH regulator: appropriate
Water for injection: 2000ml
Preparation method is with embodiment 1.
Comparative examples 4:
Cefobutazine sodium: 40g
Citric acid: 10g
Vitamin B1: 5g
Polysorbate 40: 30g
PH regulator: appropriate
Water for injection: 2000ml
Preparation method is with embodiment 1.
Comparative examples 5:
Cefobutazine sodium: 42g
Sorbitol: 4.3g
Lysine: 8.5g
Macrogol 2000: 48g
PH regulator: appropriate
Water for injection: 2000ml
Preparation method is with embodiment 1.
Comparative examples 6:
Commercially available ceftezole sodium injection (HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory, lot number: 030603)
Comparative examples 7:
Ceftezole sodium agent disclosed in CN 103271878A
Adjuvant type and the consumption of use in embodiment 1 have all been made change by comparative examples 1-7, and concrete situation of change is converged
Total as follows:
| Group | Situation of change |
| Embodiment 1 | - |
| Comparative example 1 | Without citric acid |
| Comparative example 2 | Without vitamin B1 |
| Comparative example 3 | Without polysorbate 40 |
| Comparative example 4 | Each Ingredient Amount changes |
| Comparative example 5 | Adjuvant becomes sorbitol, lysine and Macrogol 2000 |
| Comparative example 6 | Commercially available prod |
| Comparative example 7 | CN 103271878A |
The product that above-described embodiment prepares is positioned in 60 DEG C of climatic chambers, in sampling calibrating in the 5th, 10 days, result
Compared with 0 day:
There are related substance, content by high effective liquid chromatography for measuring (being shown in Table 1).
Table 1
Result shows: embodiment 1 compares with comparative examples 1-7, and pH, to have related substance, stable content to have the most excellent
Gesture, citric acid and vitamin B1 and being used in combination of polysorbate 40 have relatively been used alone obvious advantage.
Ceftezole sodium injection prepared by the embodiment of the present invention 1 and comparative examples 1-7 ceftezole sodium injection
Carry out long-time stability investigation (25 DEG C ± 2 DEG C, RH 60% ± 10%), the results are shown in Table 2:
Table 2
Result shows: ceftezole sodium injection (embodiment 1) prepared by the present invention is compared with comparative examples 1-7, matter
Amount stability increases significantly.
Being shown by above-mentioned accelerated test and long term test, the present invention has selected the cephalo of specific adjuvant and specific consumption to replace
Azoles sodium injection has extraordinary stability, and will not produce precipitation in long-term placement process, it is simple to hospital uses.And
The ceftezole sodium injection of comparative examples 1-7, either changes adjuvant type, still changes supplementary product consumption, all can
Significantly reduce the stability of injection, injection produces precipitation.
Claims (1)
1. a ceftezole sodium injection, it is made up of following raw material: 42g cefobutazine sodium, 4.3g citric acid, 8.5g tie up raw
Element B1,48g polysorbate 40,2000ml water for injection；Adjust pH to 6.4～6.5；
Described ceftezole sodium injection is prepared by following methods:
(1) taking citric acid and the vitamin B1 of recipe quantity, add the water for injection of 50% amount, be heated to 50～55 DEG C, stirring makes it
Dissolving, the cefobutazine sodium taking recipe quantity adds in solution, continues stirring 15 minutes after stirring and dissolving；
(2) take the polysorbate 40 of recipe quantity, add the water for injection of 40% amount, stir 15 minutes, adjust PH extremely with 1mol/L hydrochloric acid
3.7～4.0；
(3) 1,2 solution are merged, adjust PH to 6.4～6.5 with the sodium hydroxide solution of 1mol/L, add to the full amount of water for injection, add
The needle-use activated carbon of 0.15%, stirs 25 minutes, filtration decarburization, intermediate inspection, qualified rear degerming with 0.22 μm membrane filtration；
(4) pour in the ampoule bottle of 2ml respectively by specification, inflated with nitrogen, sealing by fusing, 121 DEG C of moist heat sterilizations 15 minutes, it is qualified to check
After, packaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510138069.5A CN104721190B (en) | 2015-03-26 | 2015-03-26 | Ceftezole sodium injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510138069.5A CN104721190B (en) | 2015-03-26 | 2015-03-26 | Ceftezole sodium injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104721190A CN104721190A (en) | 2015-06-24 |
| CN104721190B true CN104721190B (en) | 2017-01-11 |
Family
ID=53445990
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510138069.5A Expired - Fee Related CN104721190B (en) | 2015-03-26 | 2015-03-26 | Ceftezole sodium injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104721190B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525960A (en) * | 2012-01-16 | 2012-07-04 | 湖北济生医药有限公司 | Pantoprazole sodium medicinal composition and preparation method thereof |
| CN103202805A (en) * | 2013-03-22 | 2013-07-17 | 东北制药集团股份有限公司 | Vinpocetine-containing pharmaceutical composition for injection and preparation method thereof |
| CN103271878A (en) * | 2012-12-18 | 2013-09-04 | 张宏民 | Ceftezole sodium agent and preparation method thereof |
| WO2014144295A1 (en) * | 2013-03-15 | 2014-09-18 | Cubist Pharmaceuticals, Inc. | Ceftolozane antibiotic compositions |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104666252A (en) * | 2015-03-18 | 2015-06-03 | 成都汇智远景科技有限公司 | Preparation method of ceftezole sodium lyophilized powder for injection |
-
2015
- 2015-03-26 CN CN201510138069.5A patent/CN104721190B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525960A (en) * | 2012-01-16 | 2012-07-04 | 湖北济生医药有限公司 | Pantoprazole sodium medicinal composition and preparation method thereof |
| CN103271878A (en) * | 2012-12-18 | 2013-09-04 | 张宏民 | Ceftezole sodium agent and preparation method thereof |
| WO2014144295A1 (en) * | 2013-03-15 | 2014-09-18 | Cubist Pharmaceuticals, Inc. | Ceftolozane antibiotic compositions |
| CN103202805A (en) * | 2013-03-22 | 2013-07-17 | 东北制药集团股份有限公司 | Vinpocetine-containing pharmaceutical composition for injection and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104721190A (en) | 2015-06-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CS214721B2 (en) | Method of making the pentahydrate of +l6r,7r+p-7-+l+lz+p-2-+l2-aminothiazol-4-yl+p-2-+l2-carboxyprop-2-oxyimino+p acetamido+p-3-+l1-piridiniummethyl+pcef-3-em-4-carboxylate | |
| RU2524665C2 (en) | Ceftaroline-including compositions and methods of treatment | |
| KR20150135363A (en) | Ceftolozane antibiotic compositions | |
| US20140274997A1 (en) | Cephalosporin pharmaceutical compositions | |
| CN110711193A (en) | Compound amoxicillin soluble powder and preparation method thereof | |
| CN102860980A (en) | Method for preparing rocuronium bromide injection | |
| CN103044450B (en) | Ceftizoxime sodium compound and preparation method and drug composition of ceftizoxime sodium compound | |
| CN106727578A (en) | Compound Sulfachorpyrdazine Sodium Powder and preparation method thereof | |
| CN102000024A (en) | Moxifloxacin hydrochloride injection, preparation method and application thereof | |
| CN103989630A (en) | Moxifloxacin hydrochloride sodium chloride injection and preparation method thereof | |
| CN104721190B (en) | Ceftezole sodium injection and preparation method thereof | |
| WO2005120555A1 (en) | Use of human lysozyme in preparation of medicine for treating acne | |
| CN105147599B (en) | Netilmicin sulfate injection and preparation method | |
| CN103142617B (en) | Cefuroxime lysine medicinal composition | |
| CN105213301B (en) | Netilmicin sulfate injection and its quality control method | |
| CN104666252A (en) | Preparation method of ceftezole sodium lyophilized powder for injection | |
| KR102203849B1 (en) | Antibiotics composition for animals | |
| CN101972257B (en) | A kind of pharmaceutical composition containing Moxifloxacin | |
| KR101485431B1 (en) | Antibiotic Composition for Fish Comprising Amoxicillin | |
| CN102048685B (en) | Pefloxacin mesylate injection and preparation method and application thereof | |
| CN107308453B (en) | Application of cystine or cysteine and bacteriostatic agent | |
| CN102824309B (en) | Cefmetazole sodium powder for injection and preparation method thereof | |
| CN104721197A (en) | Enrofloxacin and sulfadiazine silver suspending agent and preparation method thereof | |
| CN104688742B (en) | Preparation containing cefobutazine sodium | |
| CN110917127A (en) | Method for preparing enrofloxacin injection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| CB03 | Change of inventor or designer information |
Inventor after: Xu Jie Inventor after: Huang Feng Inventor after: Yang Yuping Inventor after: Du Pengcheng Inventor after: Lu Hongmei Inventor after: An Ge Inventor after: Fu Yanru Inventor before: Liu Ying |
|
| COR | Change of bibliographic data | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20161020 Address after: Xinxiang City, Henan province 453003 Jinsui Road No. 601, Xinxiang Medical University Applicant after: Xinxiang Medical College Address before: 610000 Sichuan city of Chengdu province high tech Zone Kyrgyzstan Road No. 666 Building 2 floor 13 No. 2 Applicant before: Chengdu Hui Zhi distant view Science and Technology Ltd. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170111 Termination date: 20170326 |