CN1615871A - Gatifloxacin intra-venous trans fusion preparation and its preapring method - Google Patents
Gatifloxacin intra-venous trans fusion preparation and its preapring method Download PDFInfo
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- CN1615871A CN1615871A CN 200410080314 CN200410080314A CN1615871A CN 1615871 A CN1615871 A CN 1615871A CN 200410080314 CN200410080314 CN 200410080314 CN 200410080314 A CN200410080314 A CN 200410080314A CN 1615871 A CN1615871 A CN 1615871A
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- gatifloxacin
- injection
- preparation
- glucose
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Abstract
The intravenous Gatifloxacin transfusion preparation is freeze dried Gatifloxacin powder preparation or glucose injecta of Gatifloxacin. The preparation process includes the following steps: weighing Gatifloxacin in recipe amount and optional supplementary material, adding partial injection water and pharmaceutically acceptable acid, and stirring to dissolve; regulating pH with pharmaceutically acceptable alkali to 3.5-6.0; adding supplementary material in recipe amount, stirring to dissolve, adding injection water to full amount, adding active carbon 0.05-0.5 wt%, stirring for 20 min, eliminating carbon with 5 micron titanium rod, fine filtering with tubular filter of 0.45 micron and 0.22 micron micropore filtering film and packing; and freeze drying to prepare freeze dried preparation or directly packing and sterilizing to prepare glucose injection.
Description
Technical field
The present invention relates to Gatifloxacin venoclysis preparation and preparation method thereof.
Background technology
Gatifloxacin (C
19H
22FN
3O
4) be fluoroquinolone antibacterial agent of new generation, main by suppressing DNA gyrase and IV type topoisomerase, thus hinder bacterium DNA replication, transcribe, reparation and cell division and chromosome distribute.Experiment in vitro proof Gatifloxacin has antibacterial action to multiple common pathogen clinically, as anaerobe, mycoplasma pneumoniae and chlamydia etc. are had better antibacterial activity.External report Gatifloxacin is solid preparation (seeing HK1033281), but the solid preparation onset is slow, uses inconvenience for some particular patients ', and therefore being made into the venoclysis preparation can improve blood drug level fast, for ease of clinical use, preferably it is made as the venoclysis preparation.
Summary of the invention
The present inventor tests and finds that Gatifloxacin is atomic molten in water, and the pH value of solution has a significant impact the stability of product, all can dissolve in acidity or alkaline solution, but Gatifloxacin is unstable in alkaline solution.The inventor finds to select to be made into Gatifloxacin salt with pharmaceutically acceptable acid (comprising mineral acid and organic acid, preferred hydrochloric acid, methanesulfonic acid, tartaric acid, citric acid, lactic acid, more preferably hydrochloric acid) can increase dissolubility, is more suitable in production.Most preferably be made into the Gatifloxacin hydrochlorate.In addition, the inventor finds that active carbon also has absorption to principal agent in absorption impurity and pyrogen in preparation process, therefore need screen concentration of activated carbon.Preferred concentration of activated carbon is 0.05%～0.5%, more preferably 0.2%.The inventor also finds, the concentration of sorbitol also has certain influence to the outward appearance of Gatifloxacin lyophilized formulations in the lyophilized formulations preparation process, the concentration of sorbitol is crossed to hang down and the agglomerating phenomenon of atrophy can be occurred, the excessive concentration of sorbitol then causes wastage of material, and the amount of preferred sorbitol is 0.4～0.6 weight portion of Gatifloxacin.
An object of the present invention is to provide Gatifloxacin venoclysis preparation (comprising lyophilized formulations and glucose injection formulation) rapid-action, that quality good, stability is high; Another object of the present invention provides the preparation method of Gatifloxacin venoclysis preparation.
The invention provides the preparation method of Gatifloxacin venoclysis preparation, it may further comprise the steps:
A. take by weighing Gatifloxacin (and the adjuvant of recipe quantity, it under the situation of lyophilized formulations sorbitol, under the situation of glucose injection glucose), add part water for injection, add pharmaceutically acceptable acid (comprising mineral acid and organic acid, preferred hydrochloric acid, methanesulfonic acid, tartaric acid, citric acid, lactic acid, more preferably hydrochloric acid), stir dissolving;
B. use pharmaceutically acceptable alkali (comprising inorganic base and organic base, preferred sodium hydroxide) to transfer pH3.5～6.0 (preferred pH4.0);
C. the adjuvant that adds recipe quantity (is sorbitol under the situation of lyophilized formulations, under the situation of glucose injection glucose), stir, dissolving adds to the full amount of water for injection, and adds active carbon 0.05%～0.5% (preferred 0.2%), stirred 20 minutes, 5 μ m titanium rods take off charcoal, again through the microporous filter membrane fine straining of filter cartridge 0.45 μ m and 0.22um, and fill;
D. lyophilized formulations is made in lyophilization; Or directly embedding, glucose injection is made in sterilization.
More particularly, the preparation method of Gatifloxacin lyophilized formulations of the present invention (injection Gatifloxacin preparation) is as follows:
A. take by weighing the Gatifloxacin of recipe quantity, add part water for injection, add pharmaceutically acceptable acid, stir, dissolving;
B. use pharmaceutically acceptable adjusting PH with base 3.5～6.0 (preferred pH4.0);
C. the sorbitol that adds recipe quantity stirs, dissolving, add to the full amount of water for injection, add active carbon 0.05%～0.5% (preferred 0.2%), stirred 20 minutes, 5 μ m titanium rods take off charcoal, and through the microporous filter membrane fine straining of filter cartridge 0.45 μ m and 0.22um, fill is in cillin bottle again;
D. lyophilization;
E. fill in plug, roll lid.
The preparation method of Gatifloxacin glucose injection of the present invention is as follows:
A. the glucose that takes by weighing recipe quantity is dissolved in the part water for injection, stirs to make dissolving;
B. the Gatifloxacin that takes by weighing recipe quantity adds in the above-mentioned solution, adds pharmaceutically acceptable acid and makes medicine dissolution;
C. use pharmaceutically acceptable adjusting PH with base 3.5～6.0 (preferred pH4.0), add to the full amount of water for injection, add active carbon 0.05%～0.5% (preferred 0.2%), stirred 20 minutes, 5 μ m titanium rods take off charcoal, again through the microporous filter membrane fine straining of filter cartridge 0.45 μ m and 0.22um;
D. embedding, sterilization.
Sorbitol described in the present invention, glucose are adjuvant, and wherein sorbitol is with being excipient, and glucose is an isoosmotic adjusting agent.The preparation technology of venoclysis preparation of the present invention is feasible, reliable product quality, has good stability.
Gatifloxacin venoclysis preparation of the present invention can be lyophilized formulations or glucose injection formulation, and wherein the prescription of Gatifloxacin lyophilized formulations comprises following composition:
Gatifloxacin 1 weight portion
Sorbitol 0.4～0.6 weight portion
Preferred Gatifloxacin lyophilized formulations has following prescription:
Gatifloxacin 1 weight portion
Sorbitol 0.5 weight portion
The prescription of Gatifloxacin glucose injection formulation of the present invention comprises following composition:
Gatifloxacin 1 weight portion
Glucose 22.5～27.5 weight portions
Water for injection 450～550 weight portions
Preferred Gatifloxacin glucose injection formulation has following prescription:
Gatifloxacin 1 weight portion
Glucose 25 weight portions
Water for injection 500 weight portions
The specific embodiment.
Embodiment 1: the Gatifloxacin lyophilized formulations,
Prescription is:
(a) Gatifloxacin 40mg/ml
(b) sorbitol 20mg/ml
(c) water for injection adds to 5ml
To make 100 bottles of injection Gatifloxacin preparations is example, and concrete preparation method is as follows:
The Gatifloxacin that takes by weighing recipe quantity earlier is added in the part water for injection, and the hydrochloric acid solution that adds 1mol/L stirs, dissolving; NaOH solution with 1mol/L is regulated pH to 4.0, adds the sorbitol of recipe quantity, stirs, and dissolving adds to the full amount of water for injection; Add 0.2% ejection preparation and stir evenly with active carbon, stirred 20 minutes, 5 μ m titanium rods take off charcoal, and through the microporous filter membrane fine straining of filter cartridge 0.45 μ m and 0.22um, fill is in cillin bottle again; Lyophilization; The plug plug rolls lid.
Embodiment 2: different pH value are to the influence of Gatifloxacin aqueous stability.
Make the different Gatifloxacin aqueous solution of pH value by the method for embodiment 1.The results are shown in Table 1.
The different pH value of table 1. are to the influence of stability of solution
PH value A450nm A430nm placed 48 hours for 4 ℃
3.0 0.014 0.062 nothing is separated out
3.5 0.013 0.061 nothing is separated out
4.0 0.012 0.059 nothing is separated out
4.5 0.013 0.058 nothing is separated out
5.0 0.014 0.052 nothing is separated out
5.5 0.015 0.048 nothing is separated out
6.0 0.014 0.044 separates out
Embodiment 3: different activities charcoal concentration is to the influence of Gatifloxacin lyophilized formulations drug content.
Press the method for embodiment 1, take off charcoal with the variable concentrations active carbon and make injection Gatifloxacin preparation.The results are shown in Table 2.
Table 2. concentration of activated carbon is to the influence of Gatifloxacin lyophilized formulations drug content
Content (%) absorption back content (%) before the concentration of activated carbon absorption
0.05％ 100.8 99.7
0.2％ 100.8 98.8
0.3％ 100.8 95.3
0.5％ 100.8 88.7
Embodiment 4: the Gatifloxacin glucose injection formulation
Prescription is:
(a) Gatifloxacin 2mg/ml
(b) glucose 50mg/ml
(c) water for injection adds to 100ml
To make 100 bottles of Gatifloxacin glucose injection formulations is example, and concrete preparation method is as follows:
The glucose that takes by weighing recipe quantity earlier is added in the part water for injection, stirs dissolving; The Gatifloxacin that adds recipe quantity, the hydrochloric acid solution of adding 0.1mol/L stirs, dissolving; NaOH solution with 0.1mol/L is regulated pH to 4.0; Add to the full amount of water for injection; Add 0.2% needle-use activated carbon and stir evenly, stirred 20 minutes, 5 μ m titanium rods take off charcoal, and through the microporous filter membrane fine straining of filter cartridge 0.45 μ m and 0.22um, fill is in infusion bottle again; Sterilization.
Embodiment 5: sorbitol content is for the influence of injection Gatifloxacin preparation outward appearance.
Press the method for embodiment 1, with the formulations prepared from solutions injection Gatifloxacin preparation that contains five kinds of variable concentrations in sorbitol 20mg/ml * (1 ± 30%) mg/ml scope.The results are shown in Table 3.
Table 3. sorbitol content is for the influence of injection Gatifloxacin preparation outward appearance
Sorbitol content (mg/ml) preparation outward appearance
14 atrophys are agglomerating
16 atrophy is agglomerating slightly
18 is loose block
20 is loose block
22 is loose block
26 is loose block
Claims (10)
1. the preparation method of Gatifloxacin venoclysis preparation, it may further comprise the steps:
A. take by weighing the Gatifloxacin of recipe quantity, selectable, and adjuvant, add part water for injection, add pharmaceutically acceptable acid, stir dissolving;
B. use pharmaceutically acceptable adjusting PH with base 3.5～6.0, preferably transferring pH is 4.0;
C. the adjuvant that adds recipe quantity stirs, and dissolving adds to the full amount of water for injection, and adds active carbon 0.05%～0.5%, and is preferred 0.2%, stirs 20 minutes, and 5 μ m titanium rods take off charcoal, again through the microporous filter membrane fine straining of filter cartridge 0.45 μ m and 0.22um, and fill;
D. lyophilized formulations is made in lyophilization; Or directly embedding, glucose injection is made in sterilization.
2. according to the process of claim 1 wherein that described preparation is Gatifloxacin lyophilized formulations or glucose injection.
3. according to the method for claim 2, wherein said adjuvant is sorbitol under the situation of lyophilized formulations, is glucose under the situation of glucose injection.
4. according to the process of claim 1 wherein that described pharmaceutically acceptable acid is selected from mineral acid and organic acid, preferred hydrochloric acid, methanesulfonic acid, tartaric acid, citric acid, lactic acid, more preferably hydrochloric acid.
5. according to the process of claim 1 wherein described pharmaceutically acceptable inorganic base and the organic base of being selected from, preferred sodium hydroxide.
6. according to each method of claim 1-5, the preparation method of wherein said Gatifloxacin lyophilized formulations is as follows:
A. take by weighing the Gatifloxacin of recipe quantity, add part water for injection, add pharmaceutically acceptable acid, stir, dissolving;
B. use pharmaceutically acceptable adjusting PH with base 3.5～6.0, preferred pH4.0;
C. the sorbitol that adds recipe quantity stirs, and dissolving adds to the full amount of water for injection, add active carbon 0.05%～0.5%, preferred 0.2%, stirred 20 minutes, 5 μ m titanium rods take off charcoal, and through the microporous filter membrane fine straining of filter cartridge 0.45 μ m and 0.22um, fill is in cillin bottle again;
D. lyophilization;
E. fill in plug, roll lid.
7. according to each method of claim 1-5, the preparation method of wherein said Gatifloxacin glucose injection is as follows:
A. the glucose that takes by weighing recipe quantity is dissolved in the part water for injection, stirs to make dissolving;
B. the Gatifloxacin that takes by weighing recipe quantity adds in the above-mentioned solution, adds pharmaceutically acceptable acid and makes medicine dissolution;
C. use pharmaceutically acceptable adjusting PH with base 3.5～6.0 (preferred pH4.0), add to the full amount of water for injection, add active carbon 0.05%～0.5% (preferred 0.2%), stirred 20 minutes, 5 μ m titanium rods take off charcoal, again through the microporous filter membrane fine straining of filter cartridge 0.45 μ m and 0.22um;
D. embedding, sterilization.
8. according to the Gatifloxacin lyophilized formulations of the method for claim 6 preparation, its prescription is as follows:
Gatifloxacin 1 weight portion
Sorbitol 0.4～0.6 weight portion, preferred 0.5 weight portion
9. according to the Gatifloxacin glucose injection formulation of the method for claim 7 preparation, its prescription is as follows:
Gatifloxacin 1 weight portion
Glucose 22.5～2 7.5 weight portions,
Water for injection 450～550 weight portions
10. according to the Gatifloxacin glucose injection formulation of claim 9, its prescription is as follows:
Gatifloxacin 1 weight portion
Glucose 25 weight portions
Water for injection 500 weight portions
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410080314 CN1615871A (en) | 2004-09-28 | 2004-09-28 | Gatifloxacin intra-venous trans fusion preparation and its preapring method |
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|---|---|---|---|
| CN 200410080314 CN1615871A (en) | 2004-09-28 | 2004-09-28 | Gatifloxacin intra-venous trans fusion preparation and its preapring method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101234116B (en) * | 2006-07-21 | 2010-11-24 | 哈药集团制药总厂 | Powder needle injection containing caderofloxacin lactate |
| CN101234115B (en) * | 2006-07-21 | 2010-11-24 | 哈药集团制药总厂 | Water needle injection containing caderofloxacin lactate |
| CN103316350A (en) * | 2013-07-16 | 2013-09-25 | 南京正宽医药科技有限公司 | Gatifloxacin and sodium chloride injection and its preparation method |
| CN104274395A (en) * | 2014-09-19 | 2015-01-14 | 威海爱威制药有限公司 | Ondansetron hydrochloride sodium chloride injection and preparation method thereof |
-
2004
- 2004-09-28 CN CN 200410080314 patent/CN1615871A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101234116B (en) * | 2006-07-21 | 2010-11-24 | 哈药集团制药总厂 | Powder needle injection containing caderofloxacin lactate |
| CN101234115B (en) * | 2006-07-21 | 2010-11-24 | 哈药集团制药总厂 | Water needle injection containing caderofloxacin lactate |
| CN103316350A (en) * | 2013-07-16 | 2013-09-25 | 南京正宽医药科技有限公司 | Gatifloxacin and sodium chloride injection and its preparation method |
| CN104274395A (en) * | 2014-09-19 | 2015-01-14 | 威海爱威制药有限公司 | Ondansetron hydrochloride sodium chloride injection and preparation method thereof |
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