CN101693008A - Ofloxacin injection and preparation process thereof - Google Patents
Ofloxacin injection and preparation process thereof Download PDFInfo
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- CN101693008A CN101693008A CN200910236327A CN200910236327A CN101693008A CN 101693008 A CN101693008 A CN 101693008A CN 200910236327 A CN200910236327 A CN 200910236327A CN 200910236327 A CN200910236327 A CN 200910236327A CN 101693008 A CN101693008 A CN 101693008A
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Abstract
The invention discloses an ofloxacin injection which is prepared by ofloxacin, acetic acid, disodium tetracemate, propylene glycol and water for injection. The invention solves the problem that an ofloxacin injection hydro-acupuncture is easy to crystallize through adopting the acetic acid as cosolvent and improving the dissolvability of ofloxacin by adding the propylene glycol to regulate the polarity of solution. The injection provided by the invention has excellent quality stability, solves the problem of crystallization commonly existed in products of ofloxacin injection hydro-acupuncture, solves the weaknesses of instability and short retention period of injection, reduces the number of insoluble particles in medicine solution, and provides the effective guarantee for the safe use in clinics.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation, particularly relate to a kind of ofloxacin injection and preparation method thereof.
Background technology
Ofloxacin is a third generation carbostyril family antibacterial drugs, and its antibacterial activity, blood drug level, bioavailability and biological half-life all come other fluoroquinolones prostatitis, and untoward reaction is rare relatively.Ofloxacin has has a broad antifungal spectrum, and antibacterial activity is strong, does not have advantages such as cross resistance with other antibacterials.Most of antibacterial of enterobacteriaceae such as citrobacter genus, cloaca, clostridium perfringen, escherichia coli, Klebsiella, Proteus, Salmonella, Shigella, vibrio, yersinia etc. all there are antibacterial action preferably, multi-drug resistant bacteria is also had antibacterial activity.The drug-fast Diplococcus gonorrhoeae of penicillin, product enzyme hemophilus influenza and Moraxella had the height antibacterial activity.Ofloxacin is by acting on the A subunit of DNA of bacteria helicase, suppresses the synthetic of DNA and duplicates and cause antibacterial death, is applicable to responsive microbial urogenital infections, respiratory tract infection, gastrointestinal infection, typhoid fever etc.Levofloxacin is the levo form of ofloxacin, and its antibacterial activity in vitro is about the twice of ofloxacin.
The dosage form of oral administration administrations such as ofloxacin capsule commonly used clinically, tablet, bioavailability is lower.Be used to rescue critical patient clinically, often need to adopt injection administration.The ofloxacin injection dosage form of market and use clinically is based on bulk capacity injection (being infusion solutions), and it is low that small-volume injection (being liquid drugs injection) preparation exists the ofloxacin dissolubility, the crystalline problem of product.The process using hydrochloric acid of bibliographical information is as the cosolvent of ofloxacin, but deposit with clinical use in problem such as common product crystallization, visible foreign matters, influence product quality, cause great inconvenience for clinical use, return the patient and bring potential safety hazard and harm.
Summary of the invention
The purpose of this invention is to provide a kind of ofloxacin injection that solves the easy crystal defect of product.
Further aim of the present invention provides the preparation method of this ofloxacin injection.
For achieving the above object, technical scheme of the present invention provides a kind of ofloxacin injection, and it is made by ofloxacin, acetic acid, disodium edetate, propylene glycol and water for injection.
The present invention adopts the cosolvent of acetic acid as ofloxacin, and adds propylene glycol adjustment polarity of solvent and improve the ofloxacin dissolubility, thereby has solved the easy crystalline problem of ofloxacin injection liquid drugs injection.Wherein the amount of acetic acid of Cai Yonging and propylene glycol can be determined by the use amount of principal agent ofloxacin, and general pharmaceutical preparation personnel promptly can determine the consumption that it is suitable by the experiment of existing knowledge and limited number of time.Generally speaking, ofloxacin content high product, needs use the acetic acid and the propylene glycol of more amount; And the amount of disodium edetate also is to determine easily.
Ofloxacin injection of the present invention, its every 1000mL contain preferred oxygen Flucloxacillin 50-100g, disodium edetate 0.1-0.5g, acetic acid 50-100mL, propylene glycol 100-400mL, surplus is a water for injection.
Ofloxacin injection of the present invention, more preferably consumption is, every 1000mL contains ofloxacin 50-80g, disodium edetate 0.1-0.3g, acetic acid 50-80mL, propylene glycol 200-300mL, surplus is a water for injection.
The preparation method of above-mentioned ofloxacin injection may further comprise the steps:
(1) gets the water for injection of part amount, add in the container, add ofloxacin, the disodium edetate of described proportioning, stir and form solution A;
(2) acetate dissolution of the described proportioning of adding in above-mentioned solution A forms solution B;
(3) propylene glycol of the described proportioning of adding stirs in above-mentioned solution B, forms solution C;
(4) leave standstill after the adding active carbon stirs in solution C, take off charcoal;
(5) add to the full amount of water for injection.
In the above-mentioned preparation method, the addition sequence of each composition among solution A, B, the C adds according to above-mentioned steps, cannot add together and stir, because disodium edetate plays the effect of complexation of metal ions therein, in solution, add earlier, purpose has been complexation metal ion, thus metal ion and ofloxacin reaction avoided, cause variable color.Reuse acetic acid carried out hydrotropy after ofloxacin was made into suspension, and ofloxacin is existed with solution state.After ofloxacin becomes solution, add propylene glycol, changed polarity of solvent, make the dissolubility of ofloxacin further increase, can from solution, not separate out crystallization thereby meet low temperature.
This preparation method, step can also comprise step after (5): fine straining, fill, sterilization and packing, to obtain qualified ofloxacin injection finished product.
Technique scheme has following advantage: by the cosolvent of employing acetic acid as ofloxacin, and add propylene glycol adjustment polarity of solvent and improve the ofloxacin dissolubility, thereby solved the easy crystalline problem of ofloxacin injection liquid drugs injection.Injection provided by the invention, quality stability is good, solved the crystalline problem of ofloxacin injection liquid drugs injection product ubiquity, and injection instability, the short shortcoming of storage life have been solved, reduced the quantity of particulate matter in the drug solution, effective assurance is provided for clinical safe handling.In addition, preparation method provided by the invention is easy, convenient clinical use, and the product quality height pollutes for a short time, and side effect is little, transports easy to carry.
The specific embodiment
Below in conjunction with embodiment, the specific embodiment of the present invention is described in further detail.Following examples are used to illustrate the present invention, but are not used for limiting the scope of the invention.
Embodiment 1
Ofloxacin 50g, disodium edetate 0.1g, acetic acid 50mL, propylene glycol 100mL.Preparation method is made up of the following step:
1. get the water for injection of 300mL, add in the container, add ofloxacin, the disodium edetate of described proportioning, stir and form solution A.
2. in above-mentioned solution A, add the acetate dissolution of described proportioning, form solution B.
3. the propylene glycol that adds described proportioning in above-mentioned solution B stirs, and forms solution C.
4. in solution C, add and leave standstill after active carbon stirs, take off charcoal.
5. add the injection water to 1000mL.
The above-mentioned solution for preparing obtains qualified ofloxacin injection finished product after fine straining, fill, sterilization and packing.The finished product capacity is 2mL.
Embodiment 2
Ofloxacin 60g, disodium edetate 0.2g, acetic acid 60mL, propylene glycol 200mL.Preparation method is made up of the following step:
1. get the water for injection of 300mL, add in the container, add ofloxacin, the disodium edetate of described proportioning, stir and form solution A.
2. in above-mentioned solution A, add the acetate dissolution of described proportioning, form solution B.
3. the propylene glycol that adds described proportioning in above-mentioned solution B stirs, and forms solution C.
4. in solution C, add and leave standstill after active carbon stirs, take off charcoal.
5. add the injection water to 1000mL.
Embodiment 3
Ofloxacin 70g, disodium edetate 0.3g, acetic acid 70mL, propylene glycol 300mL.Preparation method is made up of the following step:
1. get the water for injection of 300mL, add in the container, add ofloxacin, the disodium edetate of described proportioning, stir and form solution A.
2. in above-mentioned solution A, add the acetate dissolution of described proportioning, form solution B.
3. the propylene glycol that adds described proportioning in above-mentioned solution B stirs, and forms solution C.
4. in solution C, add and leave standstill after active carbon stirs, take off charcoal.
5. add the injection water to 1000mL.
Embodiment 4
Ofloxacin 80g, disodium edetate 0.4g, acetic acid 80mL, propylene glycol 400mL.Preparation method is made up of the following step:
1. get the water for injection of proportioning total amount 300mL, add in the container, add ofloxacin, the disodium edetate of described proportioning, stir and form solution A.
2. in above-mentioned solution A, add the acetate dissolution of described proportioning, form solution B.
3. the propylene glycol that adds described proportioning in above-mentioned solution B stirs, and forms solution C.
4. in solution C, add and leave standstill after active carbon stirs, take off charcoal.
5. add the injection water to 1000mL.
Embodiment 5
Ofloxacin 90g, disodium edetate 0.5g, acetic acid 90mL, propylene glycol 400mL.Preparation method is made up of the following step:
1. get the water for injection of 300mL, add in the container, add ofloxacin, the disodium edetate of described proportioning, stir and form solution A.
2. in above-mentioned solution A, add the acetate dissolution of described proportioning, form solution B.
3. the propylene glycol that adds described proportioning in above-mentioned solution B stirs, and forms solution C.
4. in solution C, add and leave standstill after active carbon stirs, take off charcoal.
5. add the injection water to 1000mL.
Embodiment 6
Ofloxacin 100g, disodium edetate 0.3g, acetic acid 100mL, propylene glycol 400mL.Preparation method is made up of the following step:
1. get the water for injection of 300mL, add in the container, add ofloxacin, the disodium edetate of described proportioning, stir and form solution A.
2. in above-mentioned solution A, add the acetate dissolution of described proportioning, form solution B.
3. the propylene glycol that adds described proportioning in above-mentioned solution B stirs, and forms solution C.
4. in solution C, add and leave standstill after active carbon stirs, take off charcoal.
5. add the injection water to 1000mL.
The test example
Investigated the ofloxacin monomer dissolubility in hydrochloric acid, acetic acid, lactic acid respectively respectively, ofloxacin is easily molten in glacial acetic acid as a result, the dissolubility maximum.According to dissolution phenomena and investigation result, select acetic acid to be better than other acids solvent as the cosolvent of ofloxacin.Concrete data result is as follows:
The selection of table 1 cosolvent
| Lot number | The cosolvent title | Storage temperature | Resting period | The result |
| ??071029-1 | 10% hydrochloric acid | ??5℃ | 20 days | Second day almost every crystallization all appears |
| ??071029-2 | Lactic acid | ??5℃ | 20 days | Crystallization appearred in major part in the 6th day |
| ??071029-3 | Glacial acetic acid | ??5℃ | 20 days | Crystallization appears in Ahau on a small quantity |
Investigated respectively again then and used acetic acid to add the crystallization influence of propylene glycol again, the results are shown in Table 2 and table 3 as the injection of cosolvent:
Propylene glycol is to crystalline influence under 5 ℃ of storage conditions of table 2
| Lot number | The propylene glycol consumption | Storage temperature | Resting period | The result |
| ??080131-1 | ??--------- | ??5℃ | 60 days | More crystallization appearred after 25 days |
| ??080131-2 | 10% (cumulative volume) | ??5℃ | 60 days | Small amount of crystalline appears after 60 days |
| ??080131-3 | 20% (cumulative volume) | ??5℃ | 60 days | Crystallization does not appear after 60 days |
Propylene glycol is to crystalline influence under table 3 room temperature (below the 30 ℃) storage condition
| Lot number | The propylene glycol consumption | Storage temperature | Resting period | The result |
| ??080131-1 | ??--------- | Room temperature | 6 months | Crystallization appearred in 10 days |
| ??080131-2 | 10% (cumulative volume) | Room temperature | 6 months | Crystallization appearred in 30 days |
| ??080131-3 | 20% (cumulative volume) | Room temperature | 6 months | No crystallization |
Can draw from table, the injection that has added behind 20% the propylene glycol can reach best effect, after room temperature is deposited 6 months, does not also have crystallization and occurs, and meets the demand of clinical use product fully.
Annotate: the ofloxacin that relates among the present invention is the ofloxacin monomeric form.
The above only is a preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the technology of the present invention principle; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (5)
1. an ofloxacin injection is characterized in that, it is made by ofloxacin, acetic acid, disodium edetate, propylene glycol and water for injection.
2. ofloxacin injection as claimed in claim 1 is characterized in that, its every 1000mL contains ofloxacin 50-100g, disodium edetate 0.1-0.5g, acetic acid 50-100mL, propylene glycol 100-400mL, surplus is a water for injection.
3. ofloxacin injection as claimed in claim 2 is characterized in that, its every 1000mL contains ofloxacin 50-80g, disodium edetate 0.1-0.3g, acetic acid 50-80mL, propylene glycol 200-300mL, surplus is a water for injection.
4. the preparation method of each described ofloxacin injection of claim 1-3 is characterized in that, may further comprise the steps:
(1) gets the water for injection of part amount, add in the container, add ofloxacin, the disodium edetate of described proportioning, stir and form solution A;
(2) acetate dissolution of the described proportioning of adding in above-mentioned solution A forms solution B;
(3) propylene glycol of the described proportioning of adding stirs in above-mentioned solution B, forms solution C;
(4) leave standstill after the adding active carbon stirs in solution C, take off charcoal;
(5) add to the full amount of water for injection.
5. the preparation method of ofloxacin injection as claimed in claim 4 is characterized in that, also comprises step after the step (5): fine straining, sterilization.
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| Application Number | Priority Date | Filing Date | Title |
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| CN2009102363278A CN101693008B (en) | 2009-10-16 | 2009-10-16 | Ofloxacin injection and preparation process thereof |
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| CN2009102363278A CN101693008B (en) | 2009-10-16 | 2009-10-16 | Ofloxacin injection and preparation process thereof |
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| CN101693008B CN101693008B (en) | 2011-12-14 |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102961328A (en) * | 2012-12-13 | 2013-03-13 | 鼎正动物药业（天津）有限公司 | Levofloxacin injection and preparation method thereof |
| CN103830240A (en) * | 2012-11-27 | 2014-06-04 | 洛阳惠中兽药有限公司 | Fluoroquinolone medicine composition |
| CN104000777A (en) * | 2014-05-21 | 2014-08-27 | 丽珠医药集团股份有限公司 | Levofloxacin preparation |
| CN104138354A (en) * | 2013-11-30 | 2014-11-12 | 郑州百瑞动物药业有限公司 | Ofloxacin injection for animals and preparation method thereof |
| CN111317713A (en) * | 2020-04-28 | 2020-06-23 | 湖北潜江制药股份有限公司 | Preparation method of ofloxacin injection |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1032675C (en) * | 1993-01-01 | 1996-09-04 | 苏州长征制药厂 | Concentrated water solution containing spiramycin depressor for intravenous injection after dilution |
| CN1062161C (en) * | 1997-01-08 | 2001-02-21 | 大连弘丰制药厂 | Stable prescription and process of fleabane extract injection |
| CN1823782A (en) * | 2005-12-31 | 2006-08-30 | 天津生机集团 | Long effect oxyfluoroshaxin nano-capsule injection liquid for animal and its preparation method |
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2009
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103830240A (en) * | 2012-11-27 | 2014-06-04 | 洛阳惠中兽药有限公司 | Fluoroquinolone medicine composition |
| CN103830240B (en) * | 2012-11-27 | 2016-07-06 | 洛阳惠中兽药有限公司 | A kind of flouroquinolone drugs compositions |
| CN102961328A (en) * | 2012-12-13 | 2013-03-13 | 鼎正动物药业（天津）有限公司 | Levofloxacin injection and preparation method thereof |
| CN102961328B (en) * | 2012-12-13 | 2014-12-03 | 鼎正动物药业（天津）有限公司 | Levofloxacin injection and preparation method thereof |
| CN104138354A (en) * | 2013-11-30 | 2014-11-12 | 郑州百瑞动物药业有限公司 | Ofloxacin injection for animals and preparation method thereof |
| CN104000777A (en) * | 2014-05-21 | 2014-08-27 | 丽珠医药集团股份有限公司 | Levofloxacin preparation |
| CN104000777B (en) * | 2014-05-21 | 2016-06-01 | 丽珠医药集团股份有限公司 | A kind of levofloxacin preparation |
| CN111317713A (en) * | 2020-04-28 | 2020-06-23 | 湖北潜江制药股份有限公司 | Preparation method of ofloxacin injection |
| CN111317713B (en) * | 2020-04-28 | 2022-04-12 | 湖北潜江制药股份有限公司 | Preparation method of ofloxacin injection |
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| CN101693008B (en) | 2011-12-14 |
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