CN102961328B - Levofloxacin injection and preparation method thereof - Google Patents
Levofloxacin injection and preparation method thereof Download PDFInfo
- Publication number
- CN102961328B CN102961328B CN201210541282.7A CN201210541282A CN102961328B CN 102961328 B CN102961328 B CN 102961328B CN 201210541282 A CN201210541282 A CN 201210541282A CN 102961328 B CN102961328 B CN 102961328B
- Authority
- CN
- China
- Prior art keywords
- levofloxacin
- solution
- injection
- add
- emulsion
- 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.)
- Active
Links
Abstract
The invention relates to a levofloxacin injection. The levofloxacin injection is characterized in that the injection is a faint yellow solution, the pH value of the injection is 6.0-7.5, and the injection comprises the following ingredients in parts by weight: 10-20 parts of levofloxacin, and 0.1-0.3 part of chelating agent. The preparation method comprises the steps: firstly, mixing and dissolving levofloxacin and sodium hydroxide into water, then adding the chelating agent, and finally adding one or two of lactic acid and butyrate, so as to enable the solution to form a faint yellow transparent solution which is stable in property and has no crystallization separation after being stored for a long time. The transparent solution is faintly acidy, and suitable for biological environment in livestock and poultry organisms, is non-irrtant, and livestock and poultry can not be maladaptive, the levofloxacin effective component is high in content and can be directly absorbed by the livestock and poultry organisms, and the single-time administration treatment effect is good.
Description
Technical field
The invention belongs to Levaquin technical field, especially a kind of levofloxacin and preparation method thereof.
Background technology
Levofloxacin is the active quinolone antibacterial agent of optics of new generation, and its Main Function mechanism is active for hindering DNA helicase, its intensity is ofloxacin 2 times.Levofloxacin has broad-spectrum antibacterial action to comprising the gram positive bacteria of anaerobe, negative flora, to staphylococcus, enteritis Pseudomonas, micrococcus scarlatinae, Hemolytic streptococcus, enterococcus and comprise the intestinal bacterium of escherichia coli, klebsiella, Serratia, Proteus, and the non-fermentable Gram-negative of glucose flora, hemophilus influenza, gonococcus of comprising bacillus pyocyaneus etc. all show very strong antibacterial activity.
At present, hydrochlorate or lactate that take of selling the on the market injection that levofloxacin is effective ingredient is levofloxacin, its main cause is because the dissolubility of levofloxacin is poor, after must being first prepared into the hydrochlorate or lactate of Yi Rong, could form the injection of homogenizing.But the effective content of the injection existing with the form of salt is lower, must multiple injection, easily cause the discomfort of poultry.
Summary of the invention
The object of the invention is to overcome the deficiencies in the prior art, scientific formulation, a kind of levofloxacin that active constituent content is high are provided.
The technical scheme that the present invention takes is:
A levofloxacin, is characterized in that: this injection is that light yellow transparent solution and pH value are 6.0～7.5, comprises the levofloxacin of 10～20 parts, 0.1～0.3 part of chelating agen.
And, described levofloxacin account for 10～20% of injection total solution weight.
And described injection is that levofloxacin and sodium hydroxide are mixed soluble in water, then make after adding one or both in lactic acid or butanoic acid.
And described chelating agen is EDTA-Na metal-chelator.
Another object of the present invention is to provide a kind of preparation method of levofloxacin, it is characterized in that: comprise the following steps:
(1) levofloxacin adds in 40 ℃ of water, by the speed of 0.1mol/min, adds sodium hydroxide, until levofloxacin all dissolves;
(2) in step clear solution (1), add chelating agen;
(3) in step solution (2), add lactic acid or butanoic acid make solution in constantly crystallization to solution be emulsion;
(4) in step emulsion (3), continue to add lactic acid or butanoic acid to make emulsion be transformed into clear solution;
(5) will after step clear solution water standardize solution (4), make finished product.
And (5) step carries out 0.22 μ m filtering with microporous membrane afterwards.
And described chelating agen is EDTA-Na metal-chelator.
Advantage of the present invention and good effect are:
In the present invention, first that levofloxacin and sodium hydroxide is mixed soluble in water, then add one or both in lactic acid or butanoic acid, make solution form flaxen clear solution, character is stable, and long-term storage is without crystallization, and this clear solution is faintly acid, be applicable to the biotic environment in poultry body, nonirritant, poultry there will not be unconformable problem, and levofloxacin active constituent content is high, can directly by poultry body, be absorbed, single-dose therapeutic effect is good.
The specific embodiment
Below in conjunction with embodiment, the present invention is further described, and following embodiment is illustrative, is not determinate, can not limit protection scope of the present invention with following embodiment.
A levofloxacin, is characterized in that: this injection is that light yellow transparent solution and pH value are 6.0～7.5, comprises the levofloxacin of 10～20 parts, 0.1～0.3 part of chelating agen.
Wherein, levofloxacin accounts for 10～20% of injection total solution weight.Injection is that levofloxacin and sodium hydroxide are mixed soluble in water, then makes after adding one or both in lactic acid or butanoic acid.Chelating agen is EDTA-Na metal-chelator.
The preparation method of above-mentioned levofloxacin, comprises the following steps:
(1) levofloxacin adds in 40 ℃ of water, by the speed of 0.1mol/min, adds sodium hydroxide, until levofloxacin all dissolves;
(2) in step clear solution (1), add chelating agen;
(3) in step solution (2), add lactic acid or butanoic acid make solution in constantly crystallization to solution be emulsion;
(4) in step emulsion (3), continue to add lactic acid or butanoic acid to make emulsion be transformed into clear solution;
(5) will after step clear solution water standardize solution (4), make finished product.
Wherein, (5) step carries out 0.22 μ m filtering with microporous membrane afterwards.Chelating agen is EDTA-Na metal-chelator.
Embodiment 1
A kind of preparation method of levofloxacin comprises the following steps:
(1) 10 grams of levofloxacin add 50 milliliters, in 40 ℃ of waters for injection, more altogether add 5g hydrogen-oxygen according to setting speed
Change sodium, be stirred to levofloxacin and all dissolve;
(2) the EDTA-Na metal-chelator that adds 0.2 gram;
(3) add gradually 5 milliliters of 0.2M lactic acid, and slowly stir and make the continuous crystallization of solution to solution be emulsion, continue to add 5ml lactic acid to stir gradually and make emulsion be transformed into gradually clear solution;
(4) by purified water, be settled to 100 milliliters, fill after 0.22 μ m filtering with microporous membrane.
In said process, (1) step adopts the water for injection of 40 ℃ is to dissolve for auxiliary levofloxacin, adopting speed and the solid-state sodium hydroxide of 0.1mol/min is all the consumptions for meticulous control sodium hydroxide, levofloxacin can be dissolved according to certain reaction rate, while avoiding overreaction to cause the solution later stage to store, there is crystallization, evidence, can effectively improve the injection storage life after employing solid state hydrogen sodium oxide, extends the effect duration of injection.
The chelating agen that step adds in is (2) the pollution to final injection finished product for fear of the metal ion in the course of processing, and evidence, first adds chelating agen than then to add chelating agen can effectively improve the quality of final injection finished product.
After tested, the levofloxacin making is light yellow transparent solution, and pH value is 6.3, and the effective ingredient levofloxacin content in injection is 10% of injection total solution weight.
Embodiment 2
A kind of preparation method of levofloxacin comprises the following steps:
(1) 15 grams of levofloxacin add 50 milliliters, in 40 ℃ of waters for injection, more altogether add 8g sodium oxide according to setting speed, are stirred to levofloxacin and all dissolve;
(2) the EDTA-Na metal-chelator that adds 0.2 gram;
(3) adding gradually concentration is that 10 milliliters of 0.1M butanoic acid slowly stir and make the continuous crystallization of solution to solution be emulsion, continues to add 8ml butanoic acid to stir gradually and makes emulsion be transformed into gradually clear solution;
(4) by purified water, be settled to 100 milliliters, fill after 0.22 μ m filtering with microporous membrane.
After tested, the levofloxacin making is light yellow transparent solution, and pH value is 7.0, and the effective ingredient levofloxacin content in injection is 15% of injection total solution weight.
Embodiment 3
A kind of preparation method of levofloxacin comprises the following steps:
(1) 20 grams of levofloxacin add 50 milliliters, in 40 ℃ of waters for injection, more altogether add 12g sodium oxide according to setting speed, are stirred to levofloxacin and all dissolve;
(2) the EDTA-Na metal-chelator that adds 0.2 gram;
(3) adding gradually concentration is that 5 milliliters of 0.1M butanoic acid and 5 milliliters of 0.2M lactic acid slowly stir and make the continuous crystallization of solution to solution be emulsion, continues to add 8ml butanoic acid to stir gradually and makes emulsion be transformed into gradually clear solution;
(4) by purified water, be settled to 100 milliliters, fill after 0.22 μ m filtering with microporous membrane.
After tested, the levofloxacin making is light yellow transparent solution, and pH value is 7.5, and the effective ingredient levofloxacin content in injection is 20% of injection total solution weight.
Data after the injection of embodiment 1～3 is standing are as shown in table 1:
Table 1: the data after injection is standing
As known from Table 1, after long-term storage, injection character is stable, and physicochemical property does not change, and can keep the effect duration of 24 months.
Toxicity test data after the injection of embodiment 1～3 is injected pig are as shown in table 2:
Table 2: injection toxicity test data
As known from Table 2, injection is safer to pig, and gradient experimental result shows pig to have no adverse reaction, clinical use safety.
The injection clinical experiment data of embodiment 1～3 are as shown in table 3:
Animal is 20 age in days commercial meat bird 40 plumages, divide experimental group and matched group, difference artificial challenge escherichia coli, Salmonella, escherichia coli sickness rate is 95%, Salmonella sickness rate is 75%, experimental group Research of Ofloxacin in Therapy, therapeutic dose is 0.1ml/kg body weight, experimental result is as shown in table 3:
| ? | Escherichia coli | Salmonella |
| Matched group mortality rate (%) | 73.7 | 53.3 |
| Experimental group mortality rate (%) | 5.3 | —— |
Table 3: clinical experiment data
As known from Table 3, injection to treatment Salmonella infection phase cure rate can reach 100%, to the cure rate of coli-infection also up to more than 95%.
Claims (2)
1. a levofloxacin, is characterized in that: this injection is that light yellow transparent solution and pH value are 6.3～7.5, comprises the levofloxacin of 10～20 parts, 0.1～0.3 part of chelating agen;
Preparation method comprises the following steps:
(1) levofloxacin adds in 40 ℃ of water, by the speed of 0.1mol/min, adds sodium hydroxide, until levofloxacin all dissolves;
(2) in step solution (1), first add chelating agen;
(3) in step solution (2), add again lactic acid or butanoic acid make solution in constantly crystallization to solution be emulsion;
(4) in step emulsion (3), continue to add lactic acid or butanoic acid to make emulsion be transformed into clear solution;
(5) will after step clear solution water standardize solution (4), make finished product;
Described levofloxacin 10～20% of the injection total solution weight of divining by astrology;
Described chelating agen is EDTA-Na metal-chelator.
2. a kind of levofloxacin according to claim 1, is characterized in that: (5) step carries out 0.22 μ m filtering with microporous membrane afterwards.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210541282.7A CN102961328B (en) | 2012-12-13 | 2012-12-13 | Levofloxacin injection and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210541282.7A CN102961328B (en) | 2012-12-13 | 2012-12-13 | Levofloxacin injection and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102961328A CN102961328A (en) | 2013-03-13 |
| CN102961328B true CN102961328B (en) | 2014-12-03 |
Family
ID=47791948
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210541282.7A Active CN102961328B (en) | 2012-12-13 | 2012-12-13 | Levofloxacin injection and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102961328B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1853614A (en) * | 2005-04-29 | 2006-11-01 | 信谊药厂 | Decoloring method and decoloring agent for quinolone injection |
| TW200744598A (en) * | 2005-09-28 | 2007-12-16 | Daiichi Seiyaku Co | Process for the production of freeze-dried preparations containing quinolones |
| CN101690713A (en) * | 2009-09-28 | 2010-04-07 | 洛阳普莱柯生物工程有限公司 | Preparation method for carbostyril injection |
| CN101693008A (en) * | 2009-10-16 | 2010-04-14 | 蚌埠丰原涂山制药有限公司 | Ofloxacin injection and preparation process thereof |
-
2012
- 2012-12-13 CN CN201210541282.7A patent/CN102961328B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1853614A (en) * | 2005-04-29 | 2006-11-01 | 信谊药厂 | Decoloring method and decoloring agent for quinolone injection |
| TW200744598A (en) * | 2005-09-28 | 2007-12-16 | Daiichi Seiyaku Co | Process for the production of freeze-dried preparations containing quinolones |
| CN101690713A (en) * | 2009-09-28 | 2010-04-07 | 洛阳普莱柯生物工程有限公司 | Preparation method for carbostyril injection |
| CN101693008A (en) * | 2009-10-16 | 2010-04-14 | 蚌埠丰原涂山制药有限公司 | Ofloxacin injection and preparation process thereof |
Non-Patent Citations (3)
| Title |
|---|
| 刘方等.氧氟沙星注射液的制备及质量控制.《右江民族医学院学报》.2001,第23卷(第6期), * |
| 氧氟沙星注射液的制备及质量控制;刘方等;《右江民族医学院学报》;20011231;第23卷(第6期);第963页 * |
| 马红霞.注射剂的调制——氧氟沙星注射液的制备.《动物药理学实验指导》.吉林出版集团有限责任公司,2008, * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102961328A (en) | 2013-03-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2382449A1 (en) | Metal-containing compositions, preparations and uses | |
| CN102846655A (en) | Formulation and preparation method of antibacterial spray | |
| CN106309237A (en) | Hyaluronic acid private part care gel and preparation method thereof | |
| CN105056286A (en) | Liquid band-aid and preparing method thereof | |
| WO2019242044A1 (en) | Use of composite nanoparticle of carbon and copper | |
| CN109077945A (en) | Combined bacteriostat with lysozyme for cosmetics | |
| CN102405935B (en) | Protamine compounded preparation, preparation method and application thereof | |
| JP6941329B1 (en) | Marbofloxacin spray and manufacturing method | |
| CN102379841A (en) | Preparation method of furacilin solution | |
| CN102961328B (en) | Levofloxacin injection and preparation method thereof | |
| CN103120642A (en) | Gel used for skin diseases and preparation method thereof | |
| CN102614294A (en) | Compound amoxicillin suspension injection and preparation method thereof | |
| CN104147044B (en) | Composition for treating piglet staphylococcal exudative epidermitis | |
| CN108451903B (en) | A kind of Betagen Solution and preparation method thereof | |
| CN103242392B (en) | A kind of glycyrrhizic acid double salt and preparation and application thereof | |
| Vanden Bossche et al. | Synergism of the antimicrobial agents miconazole and benzoylperoxide | |
| CN102846489B (en) | Polyhexamethyleneguanidine hydrochloride iodine medicine bath liquid and preparation method thereof | |
| CN101972257B (en) | A kind of pharmaceutical composition containing Moxifloxacin | |
| CN101653448A (en) | Veterinary compound terramycin injection and preparation method thereof | |
| CN105012249A (en) | Injection rifampicin and preparing method thereof | |
| CN102204931A (en) | Amiotide eye drop containing composite bacteriostatic agent | |
| US20150079202A1 (en) | Use of patchouli extract in the preparation of compositions with an anti-microorganism effect | |
| CN101716139A (en) | Lomefloxacin hydrochloride long-acting slow-release injection solution for livestock and preparation method thereof | |
| CN103238595A (en) | Special concentrated type glutaraldehyde disinfectant for endoscopes and preparation method of special concentrated type glutaraldehyde disinfectant | |
| CN103356663A (en) | Sulfamonomethoxine-ciprofloxacin-fosfomycin combined injection for veterinary use and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: DINGZHENG XINXING BIOTECHNOLOGY (TIANJIN) CO., LTD Free format text: FORMER OWNER: DING IS ANIMAL MEDICINE (TIANJIN) CO., LTD. Effective date: 20150320 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 300402 BEICHEN, TIANJIN TO: 300000 TANGGU DISTRICT, TIANJIN |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20150320 Address after: 300000 Taifeng Tianjin economic and Technological Development Zone, Road No. 81 building two building 201 A1 Patentee after: Ding is emerging biotechnology (Tianjin) Co., Ltd. Address before: 300402 Tianjin Road, Beichen District, Tianjin Road, Beichen science and Technology Park Road, No. 1 Patentee before: Dingzheng Animal Pharmaceutical (Tianjin) Co., Ltd. |