CN101744771A - Method for preparing solid enrofloxacin nano particles - Google Patents

Method for preparing solid enrofloxacin nano particles Download PDF

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Publication number
CN101744771A
CN101744771A CN200810204719A CN200810204719A CN101744771A CN 101744771 A CN101744771 A CN 101744771A CN 200810204719 A CN200810204719 A CN 200810204719A CN 200810204719 A CN200810204719 A CN 200810204719A CN 101744771 A CN101744771 A CN 101744771A
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China
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enrofloxacin
chitosan
solution
nano particles
solid
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CN200810204719A
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Chinese (zh)
Inventor
杨先乐
龚露旸
胡鲲
黄宣运
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Shanghai Maritime University
Shanghai Ocean University
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Shanghai Maritime University
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Abstract

The invention discloses a method for preparing solid enrofloxacin nano particles, which is characterized by comprising the following steps: firstly, preparing 1 percent aqueous solution of glacial acetic acid with distilled water, and adding chitosan into the aqueous solution under a condition of magnetic stirring to dissolve the chitosan and obtain 1.5 to 2.5mg/mL solution of chitosan; secondly, adding enrofloxacin raw material medicament into the solution of chitosan, continuing performing magnetic stirring for 10min to uniformly disperse the enrofloxacin raw material medicament, adjusting the pH value to 5.0 to obtain solution of enrofloxacin chitosan; thirdly, dissolving sodium tripolyphosphate in the distilled water to prepare 1.2 to 1.8mg/mL solution of sodium tripolyphosphate, slowly dripping the solution of sodium tripolyphosphate into the solution of enrofloxacin chitosan under the condition of magnetic stirring, after dripping is finished, continuing performing magnetic stirring for 1h, immobilizing to obtain enrofloxacin chitosan nano particle suspension; and finally, filling the immobilized enrofloxacin chitosan nano particle suspension into frozen bottles, pre-freezing the bottles for 2h at the temperature of 70 DEG C below zero, vacuumizing and freeze-drying the bottles at the temperature of 50 DEG C below zero to obtain the solid enrofloxacin nano particles.

Description

A kind of preparation method of solid enrofloxacin nano particles
Technical field:
The invention belongs to the Aquatic product technical field of medicine, especially relate to a kind of preparation method of solid enrofloxacin nano particles.
Background technology:
Enrofloxacin (Enrofloxacin, ENR) have another name called the ethyl ciprofloxacin, obtained drugs approved by FDA in 1996, be fowl poultry and Aquatic product special use the 3rd generation fluoroquinolone antibacterial agent thing, can reach antibacterial effect by suppressing the DNA of bacteria helicase, have that fungicidal spectrum is wide, widely distributed in the body, do not have characteristics such as cross resistance with other drug.
At present, still to adopt with the powder be first and second conventional dosage forms of representative to enrofloxacin in generation aborning, ubiquity that bioavailability is low, the drug effect phase is short, the intestines and stomach stimulates shortcomings such as greatly, easily producing drug resistance, and resistance is poor, be subject to light, thermal response generation degraded in the processes such as drug manufacture, transportation, preservation, cause problems such as therapeutic process Chinese medicine curative effect is low, dosage increase, treatment cycle prolongation, thereby cause by aquatic products potential safety hazards such as drug residues indirectly.
Though domestic existing part all is confined to preparation and evaluation to the nanoparticle suspension, the effective scheme that can not provide this dosage form to put into production and use about the correlational study of chitosan as carrier.
Summary of the invention:
The preparation method that the purpose of this invention is to provide a kind of solid enrofloxacin nano particles, this method can realize that little, the heavy good dispersion of nanoparticle, envelop rate and drug loading are higher, and can improve the sustained release performance of medicine and the medicine resistance to light, heat.
The preparation method of solid enrofloxacin nano particles of the present invention comprises the following steps: to achieve the above object
(1) being mixed with concentration with distilled water is 1% glacial acetic acid aqueous solution, under the condition of magnetic agitation, adds chitosan again, makes its dissolving, chitosan concentration be the chitosan solution of 1.5-2.5mg/mL;
(2) the enrofloxacin crude drug is added in the above-mentioned chitosan solution, and keep magnetic agitation it to be uniformly dispersed in 10 minutes, pH to 5.0 is regulated in the back, obtains the enrofloxacin chitosan solution;
(3) sodium tripolyphosphate is dissolved in the distilled water, be mixed with the sodium tripolyphosphate solution that concentration is 1.2-1.8mg/mL, and it is slowly splashed in the above-mentioned enrofloxacin chitosan solution under the magnetic agitation state, be added dropwise to complete back continuation magnetic agitation and fixed in 1 hour, get enrofloxacin chitosan nano suspension;
(4) the enrofloxacin chitosan nano suspension of said fixingization is sub-packed in the freezing bottle, ,-50 ℃ of following evacuation lyophilizations, makes solid enrofloxacin nano particles at last then-70 ℃ of following precoolings 2 hours.
The adjusting of described pH value is regulated with the NaOH solution of 1.0mol/L.The mass ratio of described chitosan, enrofloxacin and sodium tripolyphosphate is 10: 2: 1-8: 4: 3.The mixing speed of described magnetic agitation is 800rpm.The envelop rate of described solid enrofloxacin nano particles is 50-70%, and drug loading is 8-12wt%.
The preparation method of solid enrofloxacin nano particles of the present invention has following characteristics:
1; the chitosan that the present invention adopts is the product of de-acetyl chitin; have favorable biological degradability and bioadhesive; the energy prolong drug is in the holdup time of absorption site; improve bioavailability of medicament; in the research of drug delivery system, have widely and use; in addition; chitosan also can improve the body non-specific immunity; prepare nanoparticle with chitosan as carrier material; raw material sources are extensive; degradability is good; and its preparation process need not to add any organic formulations, and all adjuvants are nontoxic, has good use value in the development and application of high-efficiency low-toxicity fisheries drug dosage form.
2, the sodium tripolyphosphate of the present invention's employing has anion, can produce the ionomer effect with chitosan positive charge amino group, forms compound polyelectrolyte.Anion is relevant with cation concn in gelation process in the ionic cross-linking and the system, so nanoparticle only forms in specific chitosan and sodium tripolyphosphate concentration range.
3, in the process of preparation solid enrofloxacin nano particles, optimized the condition that ionic cross-linking prepares enrofloxacin chitosan nano suspension, and prepared solid enrofloxacin nano particles in conjunction with freeze-drying, make it have smaller particle size, there is not agglomeration between the nanoparticle, and higher entrapment and drug loading;
4, compare with the enrofloxacin powder and have the good slow release performance, it is 1 release that can reduce about 60% medicine in little under external environment, and total release was 79.9% in 24 hours;
5, compare with the enrofloxacin powder and have better resistance, reduced 38.4% and 13.3% respectively at 4 hours interior-heat degradation rates and ultraviolet degradation rate;
6, the present invention is easy and simple to handle, and curing is reliable, enhances productivity, and reduces production costs, for large-scale production with apply valid approach is provided.
Description of drawings:
The present invention is provided by following embodiment and accompanying drawing thereof.
Fig. 1 is the transmission electron microscope picture of solid enrofloxacin nano particles.
Fig. 2 is the release in vitro characteristics figure of solid enrofloxacin nano particles.
Fig. 3 is the thermal degradation rate figure of solid enrofloxacin nano particles.
Fig. 4 is the ultraviolet degradation rate figure of solid enrofloxacin nano particles.
The specific embodiment:
Below will the preparation method of a kind of solid enrofloxacin nano particles of the present invention be described in further detail.
Embodiment
1, take by weighing the chitosan of 40mg, it is fixed molten to 20mL to add distilled water, adds the 0.2mL glacial acetic acid and makes its dissolving, is mixed with the chitosan solution that concentration is 2mg/mL, and above-mentioned low whipping speed is to carry out under the condition of magnetic agitation of 800rpm;
2, take by weighing the enrofloxacin crude drug of 12mg, add in the above-mentioned described chitosan solution and dissolve, continue magnetic agitation with 800rpm speed and made that each component is uniformly dispersed in the solution in 10 minutes, regulate pH to 5.0 with the NaOH solution of 1.0mol/L, the enrofloxacin chitosan solution;
3, take by weighing sodium tripolyphosphate 10mg, be dissolved in the 8mL distilled water, be mixed with the sodium tripolyphosphate solution that concentration is 1.25mg/mL;
4, the 8mL sodium tripolyphosphate solution is slowly splashed in the above-mentioned enrofloxacin chitosan solution, continue magnetic agitation with 800rpm speed therebetween, make the slightly white opalescence of liquid in the beaker, after being added dropwise to complete, continue magnetic agitation with 800rpm speed again and fixed in 1 hour, get enrofloxacin chitosan nano suspension;
5, the enrofloxacin chitosan nano suspension with said fixingization is sub-packed in the freezing bottle;-70 ℃ of following precoolings 2 hours; then-50 ℃ of following evacuation lyophilizations; make solid enrofloxacin nano particles; described solid enrofloxacin nano particles and to be the porous white solid of surface porosity granular; the envelop rate of described solid enrofloxacin nano particles is 50-70%, and drug loading is 8-12wt%.
To the made solid enrofloxacin nano particles of the present invention, measure its sign, release feature and heat, light stability with transmission electron microscope (TEM), ultraviolet spectrophotometer instruments such as (UV), the result shows as follows:
Prepared solid enrofloxacin nano particles is soccer star or class spherical particles, is uniformly dispersed, and no agglomeration, mean diameter is seen accompanying drawing 1 about 237.4nm.
Prepared solid enrofloxacin nano particles has certain slow releasing function, sees accompanying drawing 2.
Compare the enrofloxacin powder, solid enrofloxacin nano particles has better heat stability, sees accompanying drawing 3.
Compare the enrofloxacin powder, solid enrofloxacin nano particles has better light stability, sees accompanying drawing 4.

Claims (5)

1. the preparation method of a solid enrofloxacin nano particles is characterized in that this method comprises the following steps:
(1) being mixed with concentration with distilled water is 1% glacial acetic acid aqueous solution, under the condition of magnetic agitation, adds chitosan again, makes its dissolving, chitosan concentration be the chitosan solution of 1.5-2.5mg/mL;
(2) the enrofloxacin crude drug is added in the above-mentioned chitosan solution, and keep magnetic agitation it to be uniformly dispersed in 10 minutes, pH to 5.0 is regulated in the back, obtains the enrofloxacin chitosan solution;
(3) sodium tripolyphosphate is dissolved in the distilled water, be mixed with the sodium tripolyphosphate solution that concentration is 1.2-1.8mg/mL, and it is slowly splashed in the above-mentioned enrofloxacin chitosan solution under the magnetic agitation state, be added dropwise to complete back continuation magnetic agitation and fixed in 1 hour, get enrofloxacin chitosan nano suspension;
(4) the enrofloxacin chitosan nano suspension of said fixingization is sub-packed in the freezing bottle, ,-50 ℃ of following evacuation lyophilizations, makes solid enrofloxacin nano particles at last then-70 ℃ of following precoolings 2 hours.
2. the preparation method of a kind of solid enrofloxacin nano particles according to claim 1 is characterized in that the adjusting of described pH value is regulated with the NaOH solution of 1.0mol/L.
3. the preparation method of a kind of solid enrofloxacin nano particles according to claim 1, the mass ratio that it is characterized in that described chitosan, enrofloxacin and sodium tripolyphosphate is 10: 2: 1-8: 4: 3.
4. the preparation method of a kind of solid enrofloxacin nano particles according to claim 1, the mixing speed that it is characterized in that described magnetic agitation is 800rpm.
5. the preparation method of a kind of solid enrofloxacin nano particles according to claim 1, the envelop rate that it is characterized in that described solid enrofloxacin nano particles is 50-70%, drug loading is 8-12wt%.
CN200810204719A 2008-12-17 2008-12-17 Method for preparing solid enrofloxacin nano particles Pending CN101744771A (en)

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102166376A (en) * 2011-04-19 2011-08-31 重庆医科大学 Ophthalmic medicine-carried amnion and preparation method thereof
CN103169665A (en) * 2012-11-23 2013-06-26 杭州师范大学 Oxaliplatin chitosan nanoparticle and application thereof
CN103536555A (en) * 2013-10-15 2014-01-29 海南卫康制药(潜山)有限公司 Ceftriaxone sodium composition freeze-dried powder for injection
CN103536558A (en) * 2013-10-15 2014-01-29 海南卫康制药(潜山)有限公司 Cefoperazone sodium composition freeze-dried powder for injection
CN103536564A (en) * 2013-10-15 2014-01-29 海南卫康制药(潜山)有限公司 Cefonicid sodium composition powder for injection
CN103536556A (en) * 2013-10-15 2014-01-29 海南卫康制药(潜山)有限公司 Pefloxacin mesylate composition freeze-dried powder for injection
CN103550176A (en) * 2013-10-15 2014-02-05 海南卫康制药(潜山)有限公司 Fosfomycin sodium composition lyophilized powder for injection
CN103585116A (en) * 2013-10-15 2014-02-19 海南卫康制药(潜山)有限公司 Levofloxacin composition freeze-dried powder for injection
CN109172802A (en) * 2018-09-21 2019-01-11 岭南师范学院 A kind of Tilapia mossambica fish gill antibacterial peptide chitosan nanoparticle and its preparation method and application
CN110141558A (en) * 2019-05-29 2019-08-20 四川农业大学 A kind of preparation method of marbofloxacin nanoparticle
CN111249251A (en) * 2018-12-03 2020-06-09 华中农业大学 Enrofloxacin chitosan nanoparticles

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102166376A (en) * 2011-04-19 2011-08-31 重庆医科大学 Ophthalmic medicine-carried amnion and preparation method thereof
CN102166376B (en) * 2011-04-19 2013-12-11 重庆医科大学 Ophthalmic medicine-carried amnion and preparation method thereof
CN103169665A (en) * 2012-11-23 2013-06-26 杭州师范大学 Oxaliplatin chitosan nanoparticle and application thereof
CN103536555A (en) * 2013-10-15 2014-01-29 海南卫康制药(潜山)有限公司 Ceftriaxone sodium composition freeze-dried powder for injection
CN103536558A (en) * 2013-10-15 2014-01-29 海南卫康制药(潜山)有限公司 Cefoperazone sodium composition freeze-dried powder for injection
CN103536564A (en) * 2013-10-15 2014-01-29 海南卫康制药(潜山)有限公司 Cefonicid sodium composition powder for injection
CN103536556A (en) * 2013-10-15 2014-01-29 海南卫康制药(潜山)有限公司 Pefloxacin mesylate composition freeze-dried powder for injection
CN103550176A (en) * 2013-10-15 2014-02-05 海南卫康制药(潜山)有限公司 Fosfomycin sodium composition lyophilized powder for injection
CN103585116A (en) * 2013-10-15 2014-02-19 海南卫康制药(潜山)有限公司 Levofloxacin composition freeze-dried powder for injection
CN109172802A (en) * 2018-09-21 2019-01-11 岭南师范学院 A kind of Tilapia mossambica fish gill antibacterial peptide chitosan nanoparticle and its preparation method and application
CN111249251A (en) * 2018-12-03 2020-06-09 华中农业大学 Enrofloxacin chitosan nanoparticles
CN110141558A (en) * 2019-05-29 2019-08-20 四川农业大学 A kind of preparation method of marbofloxacin nanoparticle

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Application publication date: 20100623