CN102727451A - Cefmetazole-containing pharmaceutical composition - Google Patents
Cefmetazole-containing pharmaceutical composition Download PDFInfo
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- CN102727451A CN102727451A CN2012102254728A CN201210225472A CN102727451A CN 102727451 A CN102727451 A CN 102727451A CN 2012102254728 A CN2012102254728 A CN 2012102254728A CN 201210225472 A CN201210225472 A CN 201210225472A CN 102727451 A CN102727451 A CN 102727451A
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- cefmetazon
- sankyo
- trisodium citrate
- citrate buffer
- disodiumhydrogen
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Abstract
The invention relates to a novel pharmaceutic preparation composition, especially to an injection preparation of cefmetazole. The injection preparation comprises the following components: cefmetazole, mannitol, EDTA-Ca, vitamin C, sodium hydrogen citrate, a trisodium citrate buffer solution and water for injection.
Description
Technical field:
The present invention relates to a kind of new pharmaceutical preparations composition, particularly relate to a kind of injection preparation of Cefmetazon (Sankyo), its prescription, application and preparation method thereof.
Background technology:
Cefmetazon (Sankyo) (Cefmetazole) is claimed cefmotazole, Cefmetazole, cefmotazole, pioneer's thick forest, Cefmetazon (Sankyo), Cefmetazole again; Be second generation cephalosporin, the wide spectrum beta-lactamase that negative bacillus is produced has stability preferably.Negative bacillus such as escherichia coli, Cray uncle pneumobacillus, proteus mirabilis, Shigella, Salmonella have sensitivity preferably to these article.Gold Portugal bacterium, A organize Hemolytic streptococcus, mucositis Bradley Chinese bacterium is extremely sensitive to these article, are used for responsive microbial respiratory system infection, biliary tract infection, urinary system infection, department of obstetrics and gynecology bacterial infection, skin soft-tissue infection and operation back prevention infection etc.
At present Cefmetazon (Sankyo) is main with powder aciculiform formula mainly, but existing product is owing to receive influence of various factors, and dissolution velocity is difficult to satisfactory, owing to do not contain antiseptic, must use immediately after the dissolving.Develop a kind of Cefmetazon (Sankyo) lyophilizing ejection preparation easy to use for this reason, increase dissolution velocity, the stability problem of avoiding long storage time to produce simultaneously is favourable to the patient.
The cefmetazole sodium injection that has gone on the market is an injectable powder, but in using for avoiding the medicine variable color still to need low temperature storage.Add the activated carbon decolorizing after-filtration in addition in the production process, cause containing quantity not sufficient easily, product is deposited the easy fluctuation of pH value in the process; Have unstability, dissolution velocity is undesirable simultaneously, and the present invention is through discovering: with a certain amount of mannitol; EDTA calcium; Vitamin C is formed compound additive with DisodiumHydrogen Citrate and trisodium citrate buffer, thereby has been overcome the above-mentioned defective of prior art.
Summary of the invention:
The present invention provides a kind of pharmaceutical composition that contains the cefmetazole sodium compound, is to be the injection freeze-dried pharmaceutical formulation of active component with the Cefmetazon (Sankyo), per 1000 injections, and it is formed as follows:
Cefmetazon (Sankyo) 500-2000g;
Mannitol 50-200g;
EDTA calcium 1-3g;
Vitamin C 1-2g,
Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4;
All the other are water for injection (adding water for injection to 4L).
Compositions of the present invention, most preferred prescription is: per 1000 injections, it is formed as follows:
Cefmetazon (Sankyo) 500g;
Mannitol 100g;
EDTA calcium 2g;
Vitamin C 1.5g,
Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4,
All the other are water for injection.
Wherein, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is following: take by weighing DisodiumHydrogen Citrate 13g, trisodium citrate 60g is dissolved in the buffer solution that obtains pH value 7.0 in the 2000ml water for injection.
Compositions of the present invention, its preparation method is following: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get the Cefmetazon (Sankyo) of above-mentioned amount then, mannitol; EDTA calcium, vitamin C adding citric acid buffer dissolving, then with the water for injection standardize solution to 4000ml, the filtration of the filter membrane of via hole diameter 0.22um; After clarity is qualified, fill, half tamponade; The inlet lyophilization, packing promptly gets.
The present invention has used DisodiumHydrogen Citrate and trisodium citrate buffer to make the solution pH value that obtains of the present invention remain on 6.9-7.1, and fluctuation range is minimum, guarantees its stability.
Adopt mannitol that the powder dissolution after the lyophilizing is speeded up, it is placed the long period in use and also can not change to use EDTA calcium and vitamin C assurance, guarantees its stability.
Compositions of the present invention, its prescription obtains through screening, and screening process is following:
Table 1: with the dissolution time is the prescription screening experiment of index
Experimental technique:
The above medicine of prescription, wiring solution-forming, the capacity of packing into are the cillin bottle of 30ml, are prepared into lyophilized formulations with the method for embodiment 1, carry out dissolution experiment again.
Sample:
Each 10 bottles in the sample of each prescription, every bottle adds sodium chloride for injection solution 15ml, with hand moving.
The dissolving index:
Naked eyes see that no floccule exists for whole dissolvings.
Table 2: the dissolution velocity table of each prescription drug (minute)
| Medicine | Prescription 1 | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 |
| Dissolution velocity | 0.95±0.030 | 0.84±0.026 | 0.72±0.015 | 0.45±0.021 | 0.63±0.032 | 0.81±0.025 |
Can know that by last table 4 dissolution velocities of filling a prescription are the fastest, be fit to use.
To the freeze dried injection of buying on the market of the present invention that contains Cefmetazon (Sankyo).Carried out the research of comparative test, the result shows that stability of the present invention is superior to the product on the market.
Process three lot sample article respectively by embodiment 1 prescription, detect heavy metal and impurity content, result such as following table:
See that from test data the three batches of injection heavy metals and the impurity content of embodiment 1 are less than the medicine that has gone on the market.
The laboratory sample room temperature was placed 60 days in addition, and the fluctuation range of embodiment 1 solution pH value is 6.9-7.1, and the Cefmetazon (Sankyo) that has gone on the market is 5.7～7.4.
The dissolution velocity test:
Lyophilized injectable powder of the present invention with the preparation of the method for the embodiment of the invention 1 carries out the dissolution velocity test with the cefmetazole sodium freeze-dried powder injection that has gone on the market, result's demonstration, and the product dissolution velocity of three batches of embodiment of the invention 1 all is higher than matched group.
The storage-stable test
In conventional refrigeration temperature (2 ~ 8 ℃) storage 30 months down, is to investigate index with impurity with embodiment 1 and the U.S. azoles sodium freeze-dried powder injection of the cephalo azoles that gone on the market, carries out long-time stability and investigates test.The result sees the following form:
Different prescriptions long-time stability under 2 ~ 8 ℃ of holding conditions
| Minute | Embodiment 1 | The cefmetazole sodium freeze-dried powder injection that has gone on the market |
| 0 month | 0.9% | 0.7% |
| June | 1.0% | 0.8% |
| December | 1.1% | 1.5% |
| 18 months | 1.3% | 1.7% |
| 24 months | 1.4% | 1.8% |
Drug standard wants the content of any impurity should be greater than 1.5%.Visible by table, the sample of the more commercially available prescription preparation of the present invention is more stable, can preserve 24 months down for 2 ~ 8 ℃ in the conventional refrigeration temperature, and product quality still meets the national drug standards, and matched group can only store 12 months.
New cefmetazole for inj freeze-drying medicinal composition provided by the invention has good stability, and invariant color does not stimulate during injection, and better tolerance is dissolved multiple advantages such as rapid, easy to use, satisfies patient's needs greatly.
The specific embodiment:
Below further specify the present invention through embodiment, but not as limitation of the present invention.
Embodiment 1
Cefmetazon (Sankyo) 500g;
Mannitol 150g;
EDTA calcium 2g;
Vitamin C 1.5g,
Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4,
Water for injection adds to 4000ml
1000 bottles
Preparation: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get the Cefmetazon (Sankyo) of above-mentioned amount then, mannitol, EDTA calcium; Vitamin C adding citric acid buffer dissolving, then with the water for injection standardize solution to 4000ml, the filtration of the filter membrane of via hole diameter 0.22um; After clarity is qualified, fill, half tamponade; The inlet lyophilization, packing promptly gets.Wherein, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is following: take by weighing DisodiumHydrogen Citrate 13g, trisodium citrate 60g is dissolved in the buffer solution that obtains pH value 7.0 in the 2000ml water for injection.
Embodiment 2
Cefmetazon (Sankyo) 1000g;
Mannitol 200g;
EDTA calcium 3g;
Vitamin C 2g,
Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4
Water for injection adds to 4L
1000 bottles
Preparation: join DisodiumHydrogen Citrate and trisodium citrate buffer 1000ml earlier, get the Cefmetazon (Sankyo) of above-mentioned amount then, mannitol, EDTA calcium; Vitamin C adding citric acid buffer dissolving, then with the water for injection standardize solution to 4000ml, the filtration of the filter membrane of via hole diameter 0.22um; After clarity is qualified, fill, half tamponade; The inlet lyophilization, packing promptly gets.Wherein, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is following: take by weighing DisodiumHydrogen Citrate 13g, trisodium citrate 60g is dissolved in the buffer solution that obtains pH value 7.0 in the 2000ml water for injection.
Embodiment 3
Cefmetazon (Sankyo) 500g;
Mannitol 100g;
EDTA calcium 1g;
Vitamin C 1g,
Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4
Water for injection adds to 4L
1000 bottles
Preparation: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get the Cefmetazon (Sankyo) of above-mentioned amount then, mannitol, EDTA calcium; Vitamin C adding citric acid buffer dissolving, then with the water for injection standardize solution to 4000ml, the filtration of the filter membrane of via hole diameter 0.22um; After clarity is qualified, fill, half tamponade; The inlet lyophilization, packing promptly gets.Wherein, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is following: take by weighing DisodiumHydrogen Citrate 13g, trisodium citrate 60g is dissolved in the buffer solution that obtains pH value 7.0 in the 2000ml water for injection.
Claims (4)
1. a pharmaceutical composition that contains Cefmetazon (Sankyo) is a freeze-dried pharmaceutical formulation, per 1000 injections, and each component is formed as follows:
Cefmetazon (Sankyo) 500-2000g;
Mannitol 50-200g;
EDTA calcium 1-3g;
Vitamin C 1-2g;
Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4;
Said preparation of compositions method is following: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get Cefmetazon (Sankyo) then, mannitol; EDTA calcium, the dissolving of vitamin C adding citric acid disodium hydrogen and trisodium citrate buffer, with the water for injection standardize solution to 4000ml; The solution pH value is 7.0, and the filter membrane of via hole diameter 0.22um filters, fill; Half tamponade, lyophilization promptly gets.
2. the pharmaceutical composition of claim 1 is characterized in that, per 1000 injections, and it is formed as follows:
Cefmetazon (Sankyo) 500g;
Mannitol 150g;
EDTA calcium 2g;
Vitamin C 1.5g;
Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4;
Said preparation of compositions method is following: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get Cefmetazon (Sankyo) then, mannitol; EDTA calcium, the dissolving of vitamin C adding citric acid disodium hydrogen and trisodium citrate buffer, with the water for injection standardize solution to 4000ml; Solution pH value 7.0, via hole diameter 0.22um filter membrane filters, fill; Half tamponade, lyophilization promptly gets.
3. preparation of drug combination method that contains Cefmetazon (Sankyo) may further comprise the steps:
Cefmetazon (Sankyo) 500g;
Mannitol 150g;
EDTA calcium 2g;
Vitamin C 1.5g,
Mol ratio is DisodiumHydrogen Citrate and the trisodium citrate buffer 2000ml of 1:4,
Water for injection adds to 4000ml
1000 bottles
Preparation: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get the Cefmetazon (Sankyo) of above-mentioned amount then, mannitol, EDTA calcium; Vitamin C joins in the citrate buffer solution and dissolves, then with the water for injection standardize solution to 4000ml, the filter membrane of via hole diameter 0.22um filters; After clarity is qualified, fill, half tamponade; The inlet lyophilization, packing promptly gets.
4. method for preparing according to claim 3; It is characterized in that; The compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is following: take by weighing DisodiumHydrogen Citrate 13g, trisodium citrate 60g is dissolved in the buffer solution that obtains pH value 7.0 in the 2000ml water for injection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201210225472 CN102727451B (en) | 2012-07-03 | 2012-07-03 | Cefmetazole-containing pharmaceutical composition |
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| CN 201210225472 CN102727451B (en) | 2012-07-03 | 2012-07-03 | Cefmetazole-containing pharmaceutical composition |
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| CN102727451B CN102727451B (en) | 2013-07-03 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044459A (en) * | 2012-12-28 | 2013-04-17 | 吴秋萍 | Novel cefmetazole compound and medicine composition thereof |
| CN106749332A (en) * | 2016-12-02 | 2017-05-31 | 河北联合制药有限公司 | The production technology of ampicillin sodium crystal |
| CN107468657A (en) * | 2016-06-08 | 2017-12-15 | 重庆圣华曦药业股份有限公司 | A kind of cefmetazole for injection drug regimen |
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| JPH06122630A (en) * | 1992-10-12 | 1994-05-06 | Taiyo Yakuhin Kogyo Kk | Stable cefotiam pharmaceutical |
| CN1493293A (en) * | 2003-07-03 | 2004-05-05 | 浙江震元制药有限公司 | Cefathiamidine freeze dried agent and its preparation method |
| JP2007238491A (en) * | 2006-03-08 | 2007-09-20 | Nipro Corp | Medical preparation |
| CN101056623A (en) * | 2004-11-10 | 2007-10-17 | 巴斯利尔药物股份公司 | Stabilized freeze-dried formulation for cephalosporin derivatives |
| CN102204916A (en) * | 2011-04-07 | 2011-10-05 | 罗诚 | Pharmaceutical composition containing cefmetazole sodium compound, and preparation method thereof |
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2012
- 2012-07-03 CN CN 201210225472 patent/CN102727451B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06122630A (en) * | 1992-10-12 | 1994-05-06 | Taiyo Yakuhin Kogyo Kk | Stable cefotiam pharmaceutical |
| CN1493293A (en) * | 2003-07-03 | 2004-05-05 | 浙江震元制药有限公司 | Cefathiamidine freeze dried agent and its preparation method |
| CN101056623A (en) * | 2004-11-10 | 2007-10-17 | 巴斯利尔药物股份公司 | Stabilized freeze-dried formulation for cephalosporin derivatives |
| JP2007238491A (en) * | 2006-03-08 | 2007-09-20 | Nipro Corp | Medical preparation |
| CN102204916A (en) * | 2011-04-07 | 2011-10-05 | 罗诚 | Pharmaceutical composition containing cefmetazole sodium compound, and preparation method thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044459A (en) * | 2012-12-28 | 2013-04-17 | 吴秋萍 | Novel cefmetazole compound and medicine composition thereof |
| CN107468657A (en) * | 2016-06-08 | 2017-12-15 | 重庆圣华曦药业股份有限公司 | A kind of cefmetazole for injection drug regimen |
| CN106749332A (en) * | 2016-12-02 | 2017-05-31 | 河北联合制药有限公司 | The production technology of ampicillin sodium crystal |
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| CN102727451B (en) | 2013-07-03 |
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Effective date of registration: 20221104 Address after: No. 68, Limin West 4th Street, Limin Development Zone, Harbin, Heilongjiang 150500 Patentee after: HARBIN PHARMACEUTICAL GROUP HOLDING Co.,Ltd. Patentee after: MEDSHINE DISCOVERY Inc. Address before: No. 109, Xuefu Road, Nangan, Harbin, Heilongjiang 150046 Patentee before: MEDSHINE DISCOVERY Inc. |