CN102846550A - Preparation method for florfenicol liposome - Google Patents
Preparation method for florfenicol liposome Download PDFInfo
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- CN102846550A CN102846550A CN2012103252912A CN201210325291A CN102846550A CN 102846550 A CN102846550 A CN 102846550A CN 2012103252912 A CN2012103252912 A CN 2012103252912A CN 201210325291 A CN201210325291 A CN 201210325291A CN 102846550 A CN102846550 A CN 102846550A
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Abstract
The present invention discloses a preparation method for a florfenicol liposome. The method comprises the following steps: 1) preparing a citric acid buffer solution with a pH value of 3.5-6.0; 2) preparing a florfenicol drug liquid with a concentration of 3 mg/ml; 3) taking phospholipid and cholesterol, adding to anhydrous ethanol, carrying out water bath stirring dissolving, vaporizing the ethanol, adding the citric acid buffer solution after forming a film, carrying out water bath stirring and complete hydration, and carrying out filtration granulating through a microporous filtration membrane to obtain a blank liposome; 4) sequentially taking the blank liposome, the florfenicol drug liquid, and a NaHCO3 solution, carrying out mixing oscillation shaking, carrying out water bath thermal insulation, and cooling with cold water to obtain a liposome crude product; and 5) carrying out a low temperature high speed centrifugation treatment on the liposome crude product from the step 4) to prepare the florfenicol liposome. The preparation method of the present invention is simple and easy to perform. The florfenicol liposome prepared by the preparation method of the present invention has characteristics of increased drug solubility in water, prolonged effective action time, improved drug stability and improved drug targeting.
Description
Technical field
The invention belongs to the veterinary drug technical field, be specifically related to a kind of preparation method of florfenicol liposome.
Background technology
Florfenicol is the broad spectrum antibiotic of the special-purpose chloromycetin of a kind of veterinary drug, and main feature is has a broad antifungal spectrum, absorbs well, and is widely distributed in the body, particularly without potential induced aplastic anemia effect.But the pharmacological action of florfenicol is to enter in the bacterial cell by fat-soluble disperse, and Main Function suppresses transpeptidase in the ribosomal 50s subunit of antibacterial 70s, the growth of peptidase is obstructed, suppress the formation of peptide chain, thereby stoped the synthetic of protein, reached antibiotic purpose.This product has a broad antifungal spectrum all has potent to gram positive bacteria and gram negative bacteria and mycoplasma.
Florfenicol is mainly used in preventing and treating asthma, infectiousness pleura pneumonia, atrophic rhinitis, pig lung plague of pig etc., and the yellow and white dysentery of piglet that escherichia coli etc. are caused, enteritis, dysentery, edema disease etc. have significant curative effect; The chronic respiratory tract disease that cholera, the white scour of chicken, intractable diarrhea or antibacterial, the mycoplasma etc. that the control birds is caused by escherichia coli, Salmonella, pasteurellosis bacillus etc. cause, infective rhinitis, dyspnea etc.
The florfenicol half-life is shorter, intracellular metabolite is very fast in collective, is insoluble in water, and utilization rate is low, and liposome is a kind of target medicine carrier, can be with the florfenicol drug encapsulation in diameter be the liposome of submicron or nanometer, thus bioavailability improved the effective acting time of prolong drug, increase the stability of its character, reduce the clinical application number of times, improve cure rate, increase the wound economic benefit.
Summary of the invention
The purpose of this invention is to provide a kind of preparation method of florfenicol liposome, thereby increase its water solublity, improve bioavailability the effective acting time of prolong drug, increase its stability and targeting.
In order to realize above purpose, the technical solution adopted in the present invention is: a kind of preparation method of florfenicol liposome may further comprise the steps:
1) preparation pH is 3.5～6.0 citrate buffer solution;
2) get the refining former powder of florfenicol stirring and dissolving in methanol, making concentration is the florfenicol medicinal liquid of 3mg/ml;
3) get the phospholipid of 0.7 weight portion and the cholesterol of 0.2 weight portion, add dehydrated alcohol, 70～75 ℃ of stirring in water bath dissolvings are also waved loose ethanol, 30 parts of citrate buffer solutions that add equality of temperature after the film forming, 70～75 ℃ of stirring in water bath aquation 5～10min, stirring at room 30min subsequently fully adds distilled water to 30 part after the aquation, carry out granulate twice through filtering with microporous membrane, get blank liposome;
4) active medicine carrying: get successively blank liposome, florfenicol medicinal liquid, NaHCO
3Solution mixes vibration and shakes up, and is incubated 15min in 70～75 ℃ of water-baths, after immediately with the cold water cooling, make the florfenicol liposome crude product;
5) step 4) gained crude product is carried out the low-temperature and high-speed centrifugal treating, make florfenicol liposome.
The aperture of microporous filter membrane is 0.8 μ m in the step 3).
NaHCO in the step 4)
3The concentration of solution is 60mg/ml.
The blank liposome of getting, florfenicol medicinal liquid, NaHCO in the step 4)
3The volume ratio of solution is 2:1:1.
The centrifugal temperature of low-temperature and high-speed is 4 ℃ in the step 5), and rotating speed is 15000rpm, centrifugation time 15min.
Florfenicol liposome is through aseptic process, packing, 4 ℃ of preservations.Florfenicol liposome is concentrated, and vacuum freeze-drying makes the florfenicol liposome lyophilized formulations, and lyophilized formulations room temperature is preserved, not only the holding time long, and convenient the transportation.
Liposome is a kind of targeted drug carrier, a kind of novel form that belongs to the targeting drug-supplying system, it can be embedded in diameter with drug powder or solution is that nanoscale has in the cyto-architectural microgranule of class, this microgranule enters the autoimmune function that is mainly activated body in the animal body by reticuloendothelial system phagocytic, and the interior distribution of the body that changes encapsulated medicine, drug main will be put aside in the histoorgans such as lung, spleen, liver and bone marrow, thereby improve the therapeutic index of medicine, reduce the toxicity of therapeutic dose and the reduction medicine of medicine.
Preparation method of the present invention is by preparation citrate buffer solution, florfenicol medicinal liquid and blank liposome, the active medicine carrying, centrifuge refining, obtain the florfenicol liposome that envelop rate is high, clinical effectiveness is good, the method is simple, the florfenicol liposome of preparation, increased the water solublity of this medicine, improve bioavailability, the prolong drug half-life, increased stability and the targeting of this medicine.
The specific embodiment
Below in conjunction with the specific embodiment the present invention is elaborated:
Embodiment 1
The preparation method of the present embodiment florfenicol liposome may further comprise the steps:
1) preparation pH is 3.5 citrate buffer solution;
2) get the refining former powder of florfenicol stirring and dissolving in methanol, making concentration is the florfenicol medicinal liquid of 3mg/ml;
3) get the phospholipid of 0.7g and the cholesterol of 0.2g, add dehydrated alcohol 2ml, 70 ℃ of stirring in water bath dissolvings are also waved loose ethanol, the citrate buffer solution 30ml that adds equality of temperature after the film forming, 70 ℃ of stirring in water bath aquation 10min, stirring at room 30min fully adds distilled water to 30ml after the aquation subsequently, via hole diameter is that the filtering with microporous membrane of 0.8 μ m carries out granulate twice, gets blank liposome;
4) medicine carrying initiatively: getting successively blank liposome, florfenicol medicinal liquid, concentration by the volume ratio of 2:1:1 is the NaHCO of 60mg/ml
3Solution mixes vibration and shakes up, and is incubated 15min in 70 ℃ of water-baths, after immediately with the cold water cooling, make the florfenicol liposome crude product;
5) with step 4) gained crude product at 4 ℃, carry out low-temperature and high-speed centrifugal treating 15min under the 15000rpm condition, make florfenicol liposome.
Embodiment 2
The preparation method of the present embodiment florfenicol liposome may further comprise the steps:
1) preparation pH is 5.0 citrate buffer solution;
2) get the refining former powder of florfenicol stirring and dissolving in methanol, making concentration is the florfenicol medicinal liquid of 3mg/ml;
3) get the phospholipid of 0.7g and the cholesterol of 0.2g, add dehydrated alcohol 2ml, 72 ℃ of stirring in water bath dissolvings are also waved loose ethanol, the citrate buffer solution 30ml that adds equality of temperature after the film forming, 72 ℃ of stirring in water bath aquation 8min, stirring at room 30min fully adds distilled water to 30ml after the aquation subsequently, via hole diameter is that the filtering with microporous membrane of 0.8 μ m carries out granulate twice, gets blank liposome;
4) medicine carrying initiatively: getting successively blank liposome, florfenicol medicinal liquid, concentration by the volume ratio of 2:1:1 is the NaHCO of 60mg/ml
3Solution mixes vibration and shakes up, and is incubated 15min in 72 ℃ of water-baths, after immediately with the cold water cooling, make the florfenicol liposome crude product;
5) with step 4) gained crude product at 4 ℃, carry out low-temperature and high-speed centrifugal treating 15min under the 15000rpm condition, make florfenicol liposome.
Embodiment 3
The preparation method of the present embodiment florfenicol liposome may further comprise the steps:
1) preparation pH is 6.0 citrate buffer solution;
2) get the refining former powder of florfenicol stirring and dissolving in methanol, making concentration is the florfenicol medicinal liquid of 3mg/ml;
3) get the phospholipid of 0.7g and the cholesterol of 0.2g, add dehydrated alcohol 2ml, 75 ℃ of stirring in water bath dissolvings are also waved loose ethanol, the citrate buffer solution 30ml that adds equality of temperature after the film forming, 75 ℃ of stirring in water bath aquation 5min, stirring at room 30min fully adds distilled water to 30ml after the aquation subsequently, via hole diameter is that the filtering with microporous membrane of 0.8 μ m carries out granulate twice, gets blank liposome;
4) medicine carrying initiatively: getting successively blank liposome, florfenicol medicinal liquid, concentration by the volume ratio of 2:1:1 is the NaHCO of 60mg/ml
3Solution mixes vibration and shakes up, and is incubated 15min in 75 ℃ of water-baths, after immediately with the cold water cooling, make the florfenicol liposome crude product;
5) with step 4) gained crude product at 4 ℃, carry out low-temperature and high-speed centrifugal treating 15min under the 15000rpm condition, make florfenicol liposome.
Envelop rate detects
Florfenicol liposome solution is got 1ml in centrifuge tube, after processing through 4 ℃ of centrifugal 50min of low temperature 15000rpm, get the 0.5ml supernatant, carry out high performance liquid chromatogram and measure, as free florfenicol C
TripThe 0.5ml precipitation is as total florfenicol C in addition
Always, envelop rate=(C then
Always-C
Trip)/C
Always* 100%.Entrapment efficiency determination result such as following table 1:
Table 1 envelop rate statistical table
Clinic Case
Certain pig farm, Shandong Province, through the clinical symptoms diagnosis, the means such as laboratory diagnosis have been made a definite diagnosis the sick swinery body that mycoplasmal pneumonia of swine occurs, the clinical symptoms performance obviously, be cough, rhinorrhea, loss of appetite etc., laboratory diagnosis is mycoplasma pneumonia, random choose is 100 from sick swinery, male and female has concurrently, pig individual weight and the mental status selected are similar, be divided into four groups, embodiment 1,2,3 made refining florfenicol liposome and commercially available florfenicols (prosperous river, Hubei Bioisystech Co., Ltd) are treated, and preparation of the present invention is pressed the 3ml/kg injection, outcome record such as following table 2:
Table 2 treatment situation statistical table
Animal experiment
70 experiment level white mice are divided into matched group, test group 1,2,3,4,5,6 at random, 10 every group, raise free choice feeding, matched group injecting normal saline 3ml in barrier system; Test group 1,2,3 injection florfenicol liposome solution 3ml; Test group 4,5,6 oral florfenicol liposome solution 5ml raise a week, observe and the record clinical setting, and clinical setting statistical result is as shown in table 3.
Table 3 clinical setting statistical table
Claims (5)
1. the preparation method of a florfenicol liposome is characterized in that: may further comprise the steps:
1) preparation pH is 3.5～6.0 citrate buffer solution;
2) get the refining former powder of florfenicol stirring and dissolving in methanol, making concentration is the florfenicol medicinal liquid of 3mg/ml;
3) get the phospholipid of 0.7 weight portion and the cholesterol of 0.2 weight portion, add dehydrated alcohol, 70～75 ℃ of stirring in water bath dissolvings are also waved loose ethanol, 30 parts of citrate buffer solutions that add equality of temperature after the film forming, 70～75 ℃ of stirring in water bath aquation 5～10min, stirring at room 30min subsequently fully adds distilled water to 30 part after the aquation, carry out granulate twice through filtering with microporous membrane, get blank liposome;
4) active medicine carrying: get successively blank liposome, florfenicol medicinal liquid, NaHCO
3Solution mixes vibration and shakes up, and is incubated 15min in 70～75 ℃ of water-baths, after immediately with the cold water cooling, make the florfenicol liposome crude product;
5) step 4) gained crude product is carried out the low-temperature and high-speed centrifugal treating, make florfenicol liposome.
2. the preparation method of florfenicol liposome according to claim 1, it is characterized in that: the aperture of microporous filter membrane is 0.8 μ m in the step 3).
3. the preparation method of florfenicol liposome according to claim 1 is characterized in that: NaHCO in the step 4)
3The concentration of solution is 60mg/ml.
4. the preparation method of florfenicol liposome according to claim 1 is characterized in that: the blank liposome of getting, florfenicol medicinal liquid, NaHCO in the step 4)
3The volume ratio of solution is 2:1:1.
5. the preparation method of florfenicol liposome according to claim 1, it is characterized in that: the centrifugal temperature of low-temperature and high-speed is 4 ℃ in the step 5), and rotating speed is 15000rpm, centrifugation time 15min.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106496309A (en) * | 2016-11-24 | 2017-03-15 | 北京开景基因技术有限公司 | Microballoon antigen and preparation method thereof and the preparation method of anti-cotinine antibody |
| CN112451589A (en) * | 2020-12-18 | 2021-03-09 | 河南科技大学 | Pharmaceutical composition for treating pullorum disease and preparation method thereof |
| CN113057979A (en) * | 2019-12-31 | 2021-07-02 | 洛阳惠德生物工程有限公司 | Method for producing and preparing Bufo bufo gargarizans granule, prepared Bufo bufo gargarizans granule and application |
| CN116270668A (en) * | 2023-05-22 | 2023-06-23 | 山东天宇生物科技有限公司 | Compound doxycycline preparation |
Citations (1)
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| CN101653415A (en) * | 2009-09-01 | 2010-02-24 | 沈阳顺旺动物药业有限公司 | Florfenicol liposome preparation and preparation method thereof |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101653415A (en) * | 2009-09-01 | 2010-02-24 | 沈阳顺旺动物药业有限公司 | Florfenicol liposome preparation and preparation method thereof |
Non-Patent Citations (2)
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| 吴小宁等: "氟苯尼考脂质体制备方法初探", 《西北农业学报》, vol. 14, no. 5, 31 December 2005 (2005-12-31) * |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106496309A (en) * | 2016-11-24 | 2017-03-15 | 北京开景基因技术有限公司 | Microballoon antigen and preparation method thereof and the preparation method of anti-cotinine antibody |
| CN113057979A (en) * | 2019-12-31 | 2021-07-02 | 洛阳惠德生物工程有限公司 | Method for producing and preparing Bufo bufo gargarizans granule, prepared Bufo bufo gargarizans granule and application |
| CN112451589A (en) * | 2020-12-18 | 2021-03-09 | 河南科技大学 | Pharmaceutical composition for treating pullorum disease and preparation method thereof |
| CN116270668A (en) * | 2023-05-22 | 2023-06-23 | 山东天宇生物科技有限公司 | Compound doxycycline preparation |
| CN116270668B (en) * | 2023-05-22 | 2023-08-11 | 山东畜牧兽医职业学院 | Compound doxycycline preparation |
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Address after: 451162 Zhengzhou economic comprehensive experimentation area, Zhengzhou air port, Henan, Xingang Province Patentee after: Henan Hou Yi Industry Group Co., Ltd. Address before: 451162 Xingang, Henan, Zhengzhou, Hong Kong airport on the eastern side of the road on the eastern side of Zhengzhou Patentee before: Zhengzhou Houyi Pharmaceutical Co., Ltd. |
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Effective date of registration: 20171211 Address after: 471100 Luoyang City, Henan Province, Mengjin County, Huayang Industrial Agglomeration Area Patentee after: LUOYANG HUIDE BIO. ENGINEERING CO., LTD. Address before: 451162 Zhengzhou economic comprehensive experimentation area, Zhengzhou air port, Henan, Xingang Province Patentee before: Henan Hou Yi Industry Group Co., Ltd. |
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