CN102727451B - Cefmetazole-containing pharmaceutical composition - Google Patents
Cefmetazole-containing pharmaceutical composition Download PDFInfo
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- CN102727451B CN102727451B CN 201210225472 CN201210225472A CN102727451B CN 102727451 B CN102727451 B CN 102727451B CN 201210225472 CN201210225472 CN 201210225472 CN 201210225472 A CN201210225472 A CN 201210225472A CN 102727451 B CN102727451 B CN 102727451B
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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) claims 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 this product.Gold Portugal bacterium, A organize Hemolytic streptococcus, mucositis Bradley Chinese bacterium is extremely sensitive to this product, 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 mainly based on powder aciculiform formula, but existing product is owing to be subjected to 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 injectable powder, but in using for avoiding the medicine variable color still to need low temperature storage.Filter after adding activated carbon decolorizing in the production process in addition, cause containing quantity not sufficient easily, product deposits that pH value easily fluctuates in the process, have unstability, dissolution velocity is undesirable simultaneously, and the present invention is by 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 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 composed 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 composed 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 as follows: 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 as follows: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get the Cefmetazon (Sankyo) of above-mentioned amount then, mannitol, EDTA calcium, the dissolving of vitamin C adding citric acid buffer, use the water for injection standardize solution to 4000ml then, the filter membrane of via hole diameter 0.22um filters, after clarity is qualified, and fill, half tamponade, the inlet lyophilization, packing, namely.
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, use EDTA calcium and vitamin C to guarantee that it places the long period in use and also can not change, guarantee its stability.
Compositions of the present invention, its prescription obtains through screening, and screening process is as follows:
Table 1: be the prescription screening experiment of index with the dissolution time
Experimental technique:
Above Pei Fang medicine, 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 |
As seen from the above table, 4 dissolution velocities of filling a prescription are the fastest, are fit to use.
To the freeze dried injection of buying on the market of the present invention that contains Cefmetazon (Sankyo).Compare the research of test, the result shows that stability of the present invention is better than the product on the market.
Make three batch samples respectively by embodiment 1 prescription, detect heavy metal and impurity content, result such as following table:
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:
Carry out the dissolution velocity test with the lyophilized injectable powder of the present invention of the method for the embodiment of the invention 1 preparation and the cefmetazole sodium freeze-dried powder injection that has gone on the market, result's demonstration, 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, be 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, carry out long-time stability and investigate test.The results are shown in following table:
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%.By table as seen, 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:
Further specify the present invention by the following examples, 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, the dissolving of vitamin C adding citric acid buffer uses the water for injection standardize solution to 4000ml then, and the filter membrane of via hole diameter 0.22um filters, after clarity is qualified, fill, half tamponade, inlet lyophilization, packing, namely.Wherein, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is as follows: 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, the dissolving of vitamin C adding citric acid buffer uses the water for injection standardize solution to 4000ml then, and the filter membrane of via hole diameter 0.22um filters, after clarity is qualified, fill, half tamponade, inlet lyophilization, packing, namely.Wherein, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is as follows: 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, the dissolving of vitamin C adding citric acid buffer uses the water for injection standardize solution to 4000ml then, and the filter membrane of via hole diameter 0.22um filters, after clarity is qualified, fill, half tamponade, inlet lyophilization, packing, namely.Wherein, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is as follows: 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 freeze-dried pharmaceutical formulation, per 1000 injections, and each component is composed 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;
Described preparation of compositions method is as follows: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get Cefmetazon (Sankyo) then, mannitol, EDTA calcium, vitamin C adding citric acid disodium hydrogen and the dissolving of trisodium citrate buffer, to 4000ml, the solution pH value is 7.0 with the water for injection standardize solution, and the filter membrane of via hole diameter 0.22 μ m filters, fill, half tamponade, lyophilization, namely.
2. the pharmaceutical composition of claim 1 is characterized in that, per 1000 injections, and it is composed 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;
Described preparation of compositions method is as follows: join DisodiumHydrogen Citrate and trisodium citrate buffer 2000ml earlier, get Cefmetazon (Sankyo) then, mannitol, EDTA calcium, vitamin C adding citric acid disodium hydrogen and the dissolving of trisodium citrate buffer, with the water for injection standardize solution to 4000ml, solution pH value 7.0, via hole diameter 0.22 μ m filter membrane filters, fill, half tamponade, lyophilization, namely.
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, and uses the water for injection standardize solution to 4000ml then, and the filter membrane of via hole diameter 0.22 μ m filters, after clarity is qualified, fill, half tamponade, inlet lyophilization, packing, namely.
4. preparation method according to claim 3, it is characterized in that, the compound method of DisodiumHydrogen Citrate and trisodium citrate buffer is as follows: 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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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103044459B (en) * | 2012-12-28 | 2014-10-22 | 吴秋萍 | Novel cefmetazole compound and medicine composition thereof |
| CN107468657B (en) * | 2016-06-08 | 2020-05-05 | 重庆圣华曦药业股份有限公司 | Cefmetazole sodium pharmaceutical composition for injection |
| CN106749332B (en) * | 2016-12-02 | 2018-11-09 | 河北联合制药有限公司 | The production technology of ampicillin sodium crystal |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN102204916A (en) * | 2011-04-07 | 2011-10-05 | 罗诚 | Pharmaceutical composition containing cefmetazole sodium compound, and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH06122630A (en) * | 1992-10-12 | 1994-05-06 | Taiyo Yakuhin Kogyo Kk | Stable cefotiam pharmaceutical |
| JP2007238491A (en) * | 2006-03-08 | 2007-09-20 | Nipro Corp | Medical preparation |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN102204916A (en) * | 2011-04-07 | 2011-10-05 | 罗诚 | Pharmaceutical composition containing cefmetazole sodium compound, and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| JP特开2007-238491A 2007.09.20 |
| JP特开平6-122630A 1994.05.06 |
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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. |
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