CN104095829A - Preparation method for enrofloxacin chitosan microsphere - Google Patents
Preparation method for enrofloxacin chitosan microsphere Download PDFInfo
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- CN104095829A CN104095829A CN201410252199.7A CN201410252199A CN104095829A CN 104095829 A CN104095829 A CN 104095829A CN 201410252199 A CN201410252199 A CN 201410252199A CN 104095829 A CN104095829 A CN 104095829A
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- enrofloxacin
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Abstract
The invention relates to a preparation method for an enrofloxacin chitosan microsphere. Glutaraldehyde is adopted as the crosslinking agent to prepare the enrofloxacin chitosan drug carrying microsphere by an emulsification crosslinking method. The enrofloxacin chitosan microsphere prepared by the emulsification crosslinking method has a particle size of 21 micrometers, the microsphere surface is smooth, the sphere is slippery, the size is uniform, and the monodispersity is good. The drug loading capacity is 4.14%, and the encapsulation efficiency is 5.64%.
Description
Technical field
The present invention relates to medicine preparation field, relate in particular to a kind of enrofloxacin chitosan microball preparation method.
Background technology
Enrofloxacin (enrofloxacin, ERPX), as animal specific antimicrobial drug, is complete synthesis third generation quinolones, has been widely used in prevention and the treatment of various animal infectious diseases.Due to features such as it have efficiently, wide spectrum, and fastbacteria is few, and side effect is little, it is one of best infection class medicine for world today animal.
Enrofloxacin was in pioneering the putting on market of Bayer A.G in 1987, and China is synthesized successfully by Haikang, Guangdong animal pharmaceutical factory for 1992.Chemical name is 1-cyclopropyl-6-fluorin-4-oxygen generation-Isosorbide-5-Nitrae-dihydro-7-(4-ethyl-1-piperazinyl)-3-quinoline carboxyl; Molecular formula is C
18h
22fN
3o
3; Molecular weight is 359.4.This product is micro-yellow or off-white color crystalline powder, odorless, mildly bitter flavor.Be soluble in alkaline solution, slightly soluble in water, methanol, insoluble in ethanol; Meet photochromic fade to orange red.
In prior art, the formed chitosan microball of the preparation method of chitosan microball, often contains residuals in animal body, and human body is caused to certain injury.
In view of above-mentioned defect, creator of the present invention has obtained this creation finally through long research and practice.
Summary of the invention
The object of the present invention is to provide a kind of enrofloxacin chitosan microball preparation method, in order to overcome above-mentioned technological deficiency.
For achieving the above object, the invention provides a kind of enrofloxacin chitosan microball preparation method,
Adopt emulsion-crosslinking method, with glutaraldehyde as cross linker, prepare enrofloxacin chitosan drug-loading microsphere;
This detailed process is:
Step a, gets chitosan 1.8g and is dissolved in 3% acetum 12ml, adds 0.2003g enrofloxacin and stirs as water;
Step b, the liquid paraffin 120ml getting containing 5% sorbester p17 puts in 250ml there-necked flask, as oil phase;
Step c, water intaking is added in oil phase and adds the toluene glutaraldehyde solution 15ml containing 15% after 30 ℃ of stirring 15min of constant temperature, and 40 ℃ of stirrings of constant temperature, add 15ml toluene glutaraldehyde solution again after 2h;
Steps d, stirs and finishes rear centrifugal 3000r/min15min, goes supernatant, and with absolute ethanol washing, 3000r/min is centrifugal, removes supernatant, uses petroleum ether centrifuge washing 3 times, and by products therefrom vacuum, 40 ℃ of dry 2d, obtain yellowish-brown powder.
Further, in above-mentioned steps c, adopt driven stirring rod to stir.
Further, in above-mentioned steps a, select the chitosan of 3% concentration.
Further, in above-mentioned steps a and b, oil-water ratio is 4: 1.
Beneficial effect of the present invention is compared with prior art: it is 21 μ m that the present invention adopts enrofloxacin chitosan microball particle diameter prepared by emulsion-crosslinking method, and microsphere surface is comparatively smooth, and spheroid is round and smooth, and size is more even, and monodispersity is better; Its drug loading is 4.14%, and envelop rate is 5.64%.By the optimization to cross-linking agent, crosslinking time, the drug loading of enrofloxacin chitosan microball is increased.
Accompanying drawing explanation
Fig. 1 is the flow chart of enrofloxacin chitosan microball preparation method of the present invention;
Fig. 2 is the IR schematic diagram of enrofloxacin chitosan microball of the present invention;
Fig. 3 is enrofloxacin standard curve schematic diagram of the present invention.
The specific embodiment
Below in conjunction with accompanying drawing, to the present invention is above-mentioned, be described in more detail with other technical characterictic and advantage.
The present invention adopts emulsion-crosslinking method, with glutaraldehyde as cross linker, prepares enrofloxacin CS medicine carrying microballoons.
The detailed process of enrofloxacin chitosan microball preparation method of the present invention is:
Step a, gets chitosan 1.8g and is dissolved in 3% acetum 12ml, adds 0.2003g enrofloxacin and stirs as water;
Step b, the liquid paraffin 120ml getting containing 5% sorbester p17 puts in 250ml there-necked flask, as oil phase;
Step c, water intaking is added in oil phase and adds the toluene glutaraldehyde solution 15ml containing 15% after 30 ℃ of stirring 15min of constant temperature, and 40 ℃ of stirrings of constant temperature, add 15ml toluene glutaraldehyde solution again after 2h;
Steps d, stirs and finishes rear centrifugal 3000r/min15min, goes supernatant, and with absolute ethanol washing, 3000r/min is centrifugal, removes supernatant, uses petroleum ether centrifuge washing 3 times, and by products therefrom vacuum, 40 ℃ of dry 2d, obtain yellowish-brown powder.
In above-mentioned steps c, adopt driven stirring rod to stir, fully crosslinked, easily balling-up, spheroid is mellow and full, and the smooth effect of sphere is better.
The microsphere of selecting the chitosan of 3% concentration to make is more even.
While adopting emulsion-crosslinking method to prepare chitosan sustained-release microsphere, require to have rational oil-water ratio.Oil-water ratio is too small, and the microsphere making bumps and likely again combines each other, affects the preparation of microsphere; Oil-water ratio is excessive, increases process costs, therefore determines that oil-water ratio was at 4: 1.
Optical microscope characterizes,
The particle diameter that adopts XSZ-H3 biology microscope sem observation enrofloxacin chitosan microball, adopts object lens and eyepiece gage under the state of 400 times, and every lattice 2.3 μ m of take are unit quantity, at 30 microspheres of sequential counting within sweep of the eye, records its particle diameter and number.Calculate the mean diameter of microsphere.
Scanning electron microscope (SEM) characterizes
Medicine is placed on conductive double sided adhesive tape, blows away unnecessary powder, adopt metal spraying to process, adopt JSM-6360 scanning electron microscopic observation, amplification is respectively the form of the enrofloxacin chitosan microball of 100 times, 500 times, 2000 times.
FT-IR characterizes
With the ratio of 1: 100, enrofloxacin crude drug is mixed with KBr, agate mortar grinds, and tabletting uses VERTEX70 type Fourier transform infrared spectrometer at 4000-500cm
-1, its absorbance of scope interscan.
The drug loading of 2.4 En Nuosha star chitosan microballs and the mensuration of envelop rate
2.4.1 the preparation of buffer medium
The buffer solution of pH=1.2: take 3.6g hydrochloric acid solution adding distil water standardize solution standing in the volumetric flask of 1000ml.
Detect the selection of wavelength
HCl solution with 0.05mol/ml fully dissolves enrofloxacin, in 0-400nm wave-length coverage, carries out uv absorption length scanning, determines the maximum absorption wavelength of enrofloxacin.With veterinary drug pharmacopeia
[14]conform to.
Determining of enrofloxacin standard curve and equation of linear regression
Get enrofloxacin raw material powder precision weighing 0.0335g, be placed in 50ml volumetric flask, the HCl solution that adds 0.1mol/lpH=1.2 dissolves and is settled to scale, get respectively 0.5ml, 1.0ml, 1.5ml, 2.0ml, 2.5ml is dissolved in 50ml volumetric flask, adds 0.1mol/lHCl standardize solution and puts scale, measures 277nm place absorbance A.
The drug loading of En Nuosha star chitosan microball and the calculating of envelop rate
Drug loading: refer to that microsphere Chinese medicine weight accounts for the percentage rate of microsphere total amount.
Envelop rate: refer to that microsphere Chinese medicine weight accounts for the percentage rate of system Chinese medicine total amount.
Assay method: get the buffer solution 50ml standardize solution that adds pH=1.2 after microsphere 0.0025g fully grinds.Room temperature continuous oscillation 24h, measures absorbance, by the amount of this medicine of regression equation calculation at 277nm place.Get the content of ultraviolet spectrophotometer 277nm place pH-value determination pH enrofloxacin after supernatant
[16].
Drug loading=(microsphere Chinese medicine amount/chitosan microball weight) * 100%
Envelop rate=(medication amount/dosage in microsphere) * 100%
Interpretation of result:
Be respectively measuring in order within sweep of the eye 30 shared lattice numbers of microsphere: 30,5,11,10,7,17,8,7,6,10,5,10,7,5,5,8,14,11,4,9,5,11,7,9,10,11,8,9,12,7.
Mean diameter=(30+5+11+ ... + 12+7) * 2.3/30=21.23 μ m.
Observed result to scanning electron microscope is analyzed, and blank chitosan microball spheroid is round and smooth, surperficial hole, more hole and fold, for dissolved water is drained rear formed small hole, spherical rounding, size is more even, have compared with minimicrosphere is sticky and float on large microsphere, monodispersity is better.
After amplifying 500 times and 1000 times, medicine carrying microballoons distributes comparatively even, and size is homogeneous ball-type rounding comparatively.As amplifying 2000 times, microsphere surface is comparatively smooth, may be attached in blank microsphere fold for former medicine.Amplify 2000 times of single microspheres, microsphere has the sticky floating impurity in surface, and not washes clean of medicine is described.
IR structural analysis, refers to shown in Fig. 2, and A is the former medicine of enrofloxacin; B is the blank microsphere of chitosan; C is En Nuosha chitosan microball; D is the former medicine of chitosan.
As shown in curve in figure, represent respectively that B is that chitosan microball, D are that the former medicine of chitosan, A are that the former medicine of enrofloxacin, C are that enrofloxacin chitosan microball is at 4000～500cm
-1the infrared spectrogram in region.In figure, A enrofloxacin is at 3440cm
-1place occurs that a broad peak is the overlapping of the O-H of carboxyl and the stretching vibration characteristic peak of N-H, at 3044cm
-1place occurs that the spike of the last one is cyclopropyl, and the absworption peak of the asymmetrical stretching vibration of the C-H on phenyl ring and piperazinyl overlapping, at 2966cm
-1there is symmetrical stretching vibration absworption peak overlapping of C-H in place, at 1624cm
-1there is carbonyl characteristic absorption peak in place, in addition, and it and 1463cm
-1all the characteristic absorption peak of the basic framework of phenyl ring in the former medicine of enrofloxacin, at 1255cm
-1, 1184cm
-1place is the absworption peak of the in-plane bending vibration of C-H, 950cm
-1, 889cm
-1, 752cm
-1absworption peak for the out-of-plane bending vibration of C-H; The former medicine of D chitosan is at 3433cm
-1have one very by force, very wide absworption peak, this is-stretching vibration of OH, 1657cm
-1the absworption peak of amido link, 1381cm
-1the N-H peak of chitosan, at 1090cm
-1the absworption peak at place is C
3-C
6the C-O of hydroxyl stretches the in-plane deformation vibration absorption peak with O-H.And by the B chitosan microball after crosslinked at 1597cm
-1the absworption peak at place has almost disappeared, after this explanation chitosan and glutaraldehyde cross-linking, surface-NH2 group disappeared; B chitosan microball characteristic absorption peak is at 1572cm
-1place is the absworption peak of C=N stretching vibration, this be CS by glutaraldehyde cross-linking after the characteristic peak of formed Schiff alkali, 1070cm
-1place is the absworption peak of the bending vibration of C-H in CS pyranoid ring; 3273cm in C enrofloxacin chitosan microball
-1place is-NH
2absworption peak, 2939cm
-1place is-COOH absworption peak, 1564cm
-1place is the absworption peak of C=C in phenyl ring, 1572cm
-1for C=N stretching vibration, this be CS by glutaraldehyde cross-linking after the characteristic peak of formed Schiff alkali.The principal character peak of chitosan all occurs, shows not generate between enrofloxacin and chitosan microball new key, and is mainly the mode combination with physically trapping.
The drug loading of enrofloxacin chitosan microball and the mensuration of envelop rate;
Standard curve and equation of linear regression in enrofloxacin pH=1.2 buffer solution, enrofloxacin maximum absorption wavelength in pH=1.2 buffer medium is 277nm, the enrofloxacin standard solution of variable concentrations absorbance when wavelength is 277nm is as follows, is shown in Table 1;
The enrofloxacin standard solution of table 1 variable concentrations absorbance when wavelength is 277nm
Take concentration as abscissa, and absorbance is vertical coordinate, and drawing standard curve through linear regression, obtains regression equation and is: A=0.1149c+0.0489, R
2=0.9927, standard curve as shown in Figure 3.
The drug loading of enrofloxacin chitosan microball and the mensuration of envelop rate
By regression equation A=0.1149c+0.0489, with ultraviolet spectrophotometer, at 277nm place, measure the absorbance of enrofloxacin, calculate drug loading and the envelop rate of enrofloxacin chitosan microball, as shown in table 2.
Drug loading and the envelop rate of table 2 enrofloxacin chitosan microball
The foregoing is only preferred embodiment of the present invention, is only illustrative for invention, and nonrestrictive.Those skilled in the art is understood, and in the spirit and scope that limit, can carry out many changes to it in invention claim, revise, and even equivalence, but all will fall within the scope of protection of the present invention.
Claims (4)
1. an enrofloxacin chitosan microball preparation method, is characterized in that, adopts emulsion-crosslinking method, with glutaraldehyde as cross linker, prepares enrofloxacin chitosan drug-loading microsphere;
This detailed process is:
Step a, gets chitosan 1.8g and is dissolved in 3% acetum 12ml, adds 0.2003g enrofloxacin and stirs as water;
Step b, the liquid paraffin 120ml getting containing 5% sorbester p17 puts in 250ml there-necked flask, as oil phase;
Step c, water intaking is added in oil phase and adds the toluene glutaraldehyde solution 15ml containing 15% after 30 ℃ of stirring 15min of constant temperature, and 40 ℃ of stirrings of constant temperature, add 15ml toluene glutaraldehyde solution again after 2h;
Steps d, stirs and finishes rear centrifugal 3000r/min15min, goes supernatant, and with absolute ethanol washing, 3000r/min is centrifugal, removes supernatant, uses petroleum ether centrifuge washing 3 times, and by products therefrom vacuum, 40 ℃ of dry 2d, obtain yellowish-brown powder.
2. enrofloxacin chitosan microball preparation method according to claim 1, is characterized in that, in above-mentioned steps c, adopts driven stirring rod to stir.
3. enrofloxacin chitosan microball preparation method according to claim 2, is characterized in that, in above-mentioned steps a, selects the chitosan of 3% concentration.
4. enrofloxacin chitosan microball preparation method according to claim 3, is characterized in that, in above-mentioned steps a and b, oil-water ratio is 4: 1.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055328A (en) * | 2015-08-04 | 2015-11-18 | 福建中医药大学 | Norisoboldine chitosan microsphere and preparation method thereof |
| CN112137985A (en) * | 2019-06-28 | 2020-12-29 | 南京理工大学 | Preparation method of chitosan-carried ciprofloxacin microspheres |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101099739A (en) * | 2006-07-03 | 2008-01-09 | 肖希龙 | Enrofloxacin gelatine microball and its preparation method |
| WO2008151502A1 (en) * | 2007-06-08 | 2008-12-18 | Hainapharm Pharmaceutical Co., Ltd. Foshan | Enrofloxacin microcapsule formulation and preparation method thereof |
| CN101513543A (en) * | 2008-02-18 | 2009-08-26 | 龙脉医疗器械(北京)有限公司 | Encapsulation drug microsphere of medicament-eluting coronary artery stent and method for preparing same |
-
2014
- 2014-08-02 CN CN201410252199.7A patent/CN104095829A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101099739A (en) * | 2006-07-03 | 2008-01-09 | 肖希龙 | Enrofloxacin gelatine microball and its preparation method |
| WO2008151502A1 (en) * | 2007-06-08 | 2008-12-18 | Hainapharm Pharmaceutical Co., Ltd. Foshan | Enrofloxacin microcapsule formulation and preparation method thereof |
| CN101513543A (en) * | 2008-02-18 | 2009-08-26 | 龙脉医疗器械(北京)有限公司 | Encapsulation drug microsphere of medicament-eluting coronary artery stent and method for preparing same |
Non-Patent Citations (1)
| Title |
|---|
| 于海峰等: "星点设计-效应面优化乳化交联法制备恩诺沙星壳聚糖微球", 《应用化工》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105055328A (en) * | 2015-08-04 | 2015-11-18 | 福建中医药大学 | Norisoboldine chitosan microsphere and preparation method thereof |
| CN105055328B (en) * | 2015-08-04 | 2018-02-27 | 福建中医药大学 | A kind of norisoboldine chitosan microball and preparation method thereof |
| CN112137985A (en) * | 2019-06-28 | 2020-12-29 | 南京理工大学 | Preparation method of chitosan-carried ciprofloxacin microspheres |
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Application publication date: 20141015 |