CN105078899A - Enrofloxacin stratified high molecular taste mashing skeleton particle and preparation method thereof - Google Patents
Enrofloxacin stratified high molecular taste mashing skeleton particle and preparation method thereof Download PDFInfo
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- CN105078899A CN105078899A CN201510530739.8A CN201510530739A CN105078899A CN 105078899 A CN105078899 A CN 105078899A CN 201510530739 A CN201510530739 A CN 201510530739A CN 105078899 A CN105078899 A CN 105078899A
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Abstract
The invention discloses an enrofloxacin stratified high molecular taste mashing skeleton particle and a preparation method thereof. The enrofloxacin stratified high molecular taste mashing skeleton particle contains, by mass, 10-30% of enrofloxacin and 70-90% of auxiliary material. Slightly-soluble high molecules are utilized to prepare enrofloxacin solid dispersoid for coating enrofloxacin to form a first layer, and then chitosan and sodium alginate are utilized for mutual crosslinking to form micro-capsules for coating enrofloxacin to form a second layer, so that bitter taste caused by the fact that enrofloxacin is released and stimulates taste bud is avoided effectively. In addition, enrofloxacin is taken as a screening index of bitter taste threshold of pigs so as to simplify the production process of the enrofloxacin stratified high molecular taste mashing skeleton particle, and special equipment is not needed, so that production cost is lowered, drug loading capacity is improved, an enrofloxacin preparation which is assured in taste masking effect is provided to veterinarians clinically, palatability and bioavailability of enrofloxacin are improved, and the enrofloxacin stratified high molecular taste mashing skeleton particle is convenient for clinical use.
Description
Technical field
The invention belongs to technical field of veterinary, particularly relate to a kind of enrofloxacin cladding macromolecule taste masking skeleton microgranule and preparation method thereof.
Background technology
Enrofloxacin can be used for treating the various diseases comprising skin infection, urinary tract infection, respiratory tract infection and wound infection etc., important role in swine diseases control.In veterinary clinic, enrofloxacin, due to bitter in the mouth, uses the mode of drug administration by injection usually; but drug administration by injection often to animal bring stress, affect growth of animal, and in scale livestock farming; drug administration by injection efficiency is low, and veterinary work amount is large, thus limits its application in veterinary clinic.
The olfactory sensation of animal and the sense of taste are very sensitive, and mammal is all the more so.Report, the intraoral gustatory cell of pig reaches 1.5 ten thousand.Enrofloxacin is directly offerd medicine, and animal is refusing to eat usually, therefore adopts rational masking methods, complies with animal taste, improves animal to the amount of medicine, has the practice significance of reality in prevention and therapy Animal diseases.The now relevant report of existing many enrofloxacin odor masks, if the patent No. is that CN103222975B has reported for work the application of enrofloxacin salt in preparation pig oral formulations, patent No. CN103239497B has reported for work a kind of Enrofloxacin clathrate compound and preparation method thereof, patent No. CN102526054B has reported for work compound enrofloxacin pellets and preparation method thereof, these methods have certain improvement to palatability to a certain extent, but it is too complicated to prepare enrofloxacin salt method by chemosynthesis, by enrofloxacin is made clathrate or prepare micropill due to method single, enrofloxacin may be adsorbed on dosage surface and cause taste masking poor effect.The taste masking preparation of enrofloxacin is many at present simultaneously studies from preparation means, usually from sensory evaluation taste masking effect, lack the scientific evaluation index to its taste masking effect, in addition the bitter threshold of animal to bitter substance is normal and people is variant, and thus the taste masking preparation of enrofloxacin is still difficult reaches desirable effect.
The various bags of the enrofloxacin that existing market is produced often are attended to one thing and lose sight of another by taste masking preparation, make Clinical practice poor effect.
Summary of the invention
The object of the present invention is to provide a kind of enrofloxacin cladding macromolecule taste masking skeleton microgranule and preparation method thereof, be intended to solution prepare enrofloxacin salt method complexity by chemosynthesis or pass through the single microcapsules and microsphere taste masking weak effect of preparation, thus cause the problem of Clinical practice poor effect.
The present invention realizes like this, in order to obtain better taste masking effect, using enrofloxacin to the bitter threshold of pig as screening index, taste masking effect is reached by preparing the combination of enrofloxacin cladding macromolecule taste masking skeleton microgranule double blocking enrofloxacin and bitterness receptors, described enrofloxacin cladding macromolecule taste masking skeleton microgranule is according to mass percent: the content of enrofloxacin is 10-30%, and the content of adjuvant is 70-90%.
Another object of the present invention is to the preparation method providing a kind of enrofloxacin cladding macromolecule taste masking skeleton microgranule, the preparation method of described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises the following steps:
Step one, gets one or both of the enrofloxacin of 10-30 part and the stearic acid of 10-30 part or glyceryl monostearate or glycerol distearate, adds in organic solvent, by magnetic stirrer, makes it to dissolve, becomes solution A;
Step 2, gets emulsifying agent in purified water, and dissolving the amount become containing emulsifying agent is the solution B of 1-3%;
Step 3, solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 35-45 DEG C of temperature, insulated and stirred makes organic solvent be evaporated completely, and must be enclosed with the suspension solution of the solid dispersion of enrofloxacin;
Step 4, the sodium alginate getting 13.3 ~ 26.7 parts is dissolved in containing in the suspension solution of Enrofloxacin solid dispersion in step 3, becomes solution C;
Step 5, the calcium chloride getting the chitosan of 13.3 ~ 66.7 parts and 24-30 part is soluble in water, becomes solution D;
Step 6, is added dropwise to solution C in solution D, after solidification 5-10min, filters, washes 3 times with water, dries to the moisture of microgranule lower than 2.0% and get final product for 40 DEG C.
Further, the preparation method of described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises the following steps:
Step one, gets 0.6g enrofloxacin and 1g stearic acid, adds in 5ml dichloromethane, by magnetic stirrer, makes it to dissolve, becomes solution A;
Step 2,0.5g polyvinyl alcohol is dissolved in 50ml purified water, becomes solution B;
Step 3, solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 40 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-Stearic acid solids dispersion;
Step 4, gets 0.75g sodium alginate and is dissolved in containing in the suspension solution of enrofloxacin-Stearic acid solids dispersion in step 3, become solution C;
Step 5, gets 0.45g chitosan and 24g calcium chloride is dissolved in 300ml water, becomes solution D;
Step 6, is added dropwise to solution C in solution D, after solidification 10min, filters, washes 3 times with water, dries to moisture lower than 2% and get final product for 40 DEG C.
Further, the preparation method of described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises the following steps:
Step one, gets 0.5g enrofloxacin and 1g glyceryl monostearate, adds in 5ml dichloromethane, by magnetic stirrer, makes it to dissolve, becomes solution A;
Step 2,1g poloxamer is dissolved in 50ml purified water, becomes solution B;
Step 3, solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 38 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-glyceryl monostearate solid dispersion;
Step 4, gets 1g sodium alginate and is dissolved in containing in the suspension solution of enrofloxacin-glyceryl monostearate solid dispersion in step 3, become solution C;
Step 5, gets 0.9g chitosan and 30g calcium chloride is dissolved in 300ml water, becomes solution D;
Step 6, is added dropwise to solution C in solution D, after solidification 8min, filters, washes 3 times with water, dries to moisture lower than 2% and get final product for 40 DEG C.
Further, the preparation method of described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises the following steps:
Step one, gets 1g enrofloxacin and 1g stearic acid, adds in 5ml dichloromethane, by magnetic stirrer, makes it to dissolve, becomes solution A;
Step 2,0.5g sodium lauryl sulphate is dissolved in 50ml purified water, becomes solution B;
Step 3, solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 35 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-Stearic acid solids dispersion;
Step 4, gets 0.75g sodium alginate and is dissolved in containing in the suspension solution of enrofloxacin-Stearic acid solids dispersion in step 3, become solution C;
Step 5, gets 0.9g chitosan and 30g calcium chloride is dissolved in 300ml water, becomes solution D;
Step 6, is added dropwise to solution C in solution D, after solidification 5min, filters, washes 3 times with water, dries to moisture lower than 2% and get final product for 40 DEG C.
Enrofloxacin cladding macromolecule taste masking skeleton microgranule provided by the invention and preparation method thereof, advantage is:
1) recorded the bitterness threshold of pig to enrofloxacin scientifically and rationally, the taste masking effect assessment for obtained enrofloxacin preparation provides the objective method of science, overcomes the blindness that similar enrofloxacin preparation is evaluated for pig taste masking.
2) by pig to based on the bitterness threshold of enrofloxacin, obtained can be used for the oral enrofloxacin cladding macromolecule taste masking skeleton microgranule of pig, than independent lipid carrier solid dispersion or independent microcapsule, there is better taste masking effect, expand the Clinical practice scope of enrofloxacin.
3) enrofloxacin cladding macromolecule taste masking skeleton microgranule of the present invention not only has infallible taste masking effect, and polymeric hydantoin sodium alginate used also has enteric slow release effect to medicine, can reduce and gastrointestinal is stimulated, extend plasma concentration time, improve bioavailability, reduce administration number of times.
4) enrofloxacin cladding macromolecule taste masking skeleton microgranule production cost of the present invention is low, is applicable to industrialized great production, patent medicine low price, is conducive to clinical widely using.
Accompanying drawing explanation
Fig. 1 is the preparation method flow chart of the enrofloxacin cladding macromolecule taste masking skeleton microgranule that the embodiment of the present invention provides.
Detailed description of the invention
In order to make object of the present invention, technical scheme and advantage clearly understand, below in conjunction with embodiment, the present invention is further elaborated.Should be appreciated that specific embodiment described herein only in order to explain the present invention, be not intended to limit the present invention.
The present invention screens enrofloxacin taste masking preparation by the evaluation index of science and the bitter threshold of enrofloxacin to pig, recording pig on the basis of enrofloxacin bitterness threshold, likely making enrofloxacin be adsorbed on dosage surface in order to avoid single method for coating and causing taste masking poor effect.The present invention scientifically designs enrofloxacin cladding macromolecule taste masking skeleton microgranule, utilize slightly solubility macromolecule to prepare Enrofloxacin solid dispersion and ground floor bag quilt is carried out to enrofloxacin, and then utilize chitosan, sodium alginate is cross-linked with each other and forms microcapsule and carry out second layer bag quilt to enrofloxacin, thus efficiently avoid the release of enrofloxacin and stimulate taste bud to cause bitterness.Simultaneously the present invention strives for simplification production technology, reduces production cost, improves drug loading, for veterinary clinic provides simple and effective enrofloxacin preparation, improve the bioavailability of enrofloxacin, be convenient to Clinical practice.
Below in conjunction with accompanying drawing, application principle of the present invention is explained in detail.
According to mass percent in the enrofloxacin cladding macromolecule taste masking skeleton microgranule of the embodiment of the present invention: the content of enrofloxacin is 10-30%, and the content of adjuvant is 70-90%.
As shown in Figure 1, the preparation method of the enrofloxacin cladding macromolecule taste masking skeleton microgranule of the embodiment of the present invention comprises the following steps:
S101: get one or both of the enrofloxacin of 10-30 part and the stearic acid of 10-30 part or glyceryl monostearate or glycerol distearate, add in organic solvent, by magnetic stirrer, makes it to dissolve, becomes solution A;
S102: get emulsifying agent in purified water, dissolving the amount become containing emulsifying agent is the solution B of 1-3%;
S103: solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 35-45 DEG C of temperature, insulated and stirred makes organic solvent be evaporated completely, and must be enclosed with the suspension solution of the solid dispersion of enrofloxacin;
S104: the sodium alginate getting 13.3 ~ 26.7 parts is dissolved in containing in the suspension solution of Enrofloxacin solid dispersion in step S103, becomes solution C;
S105: the calcium chloride getting the chitosan of 13.3 ~ 66.7 parts and 24-30 part is soluble in water, becomes solution D;
S106: solution C be added dropwise in solution D, after solidification 5-10min, filters, washes 3 times with water, dries to the moisture of microgranule lower than 2.0% and get final product for 40 DEG C.
By embodiments of the invention, application principle of the present invention is described further:
Embodiment 1:
A production for enrofloxacin cladding macromolecule taste masking skeleton microgranule, comprises with step:
(1) get 0.6g enrofloxacin and 1g stearic acid, add in 5ml dichloromethane, by magnetic stirrer, make it to dissolve, become solution A;
(2) 0.5g polyvinyl alcohol is dissolved in 50ml purified water, becomes solution B;
(3) solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 40 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-Stearic acid solids dispersion;
(4) get 0.75g sodium alginate and be dissolved in containing in the suspension solution of enrofloxacin-Stearic acid solids dispersion in step (3), become solution C;
(5) get 0.45g chitosan and 24g calcium chloride is dissolved in 300ml water, become solution D;
(6) solution C is added dropwise in solution D, after solidification 10min, filters, wash 3 times with water, dry to moisture lower than 2% and get final product for 40 DEG C.
Embodiment 2:
A production for enrofloxacin cladding macromolecule taste masking skeleton microgranule, comprises with step:
(1) get 0.5g enrofloxacin and 1g glyceryl monostearate, add in 5ml dichloromethane, by magnetic stirrer, make it to dissolve, become solution A;
(2) 1g poloxamer is dissolved in 50ml purified water, becomes solution B;
(3) solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 38 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-glyceryl monostearate solid dispersion;
(4) get 1g sodium alginate and be dissolved in containing in the suspension solution of enrofloxacin-glyceryl monostearate solid dispersion in step (3), become solution C;
(5) get 0.9g chitosan and 30g calcium chloride is dissolved in 300ml water, become solution D;
(6) solution C is added dropwise in solution D, after solidification 8min, filters, wash 3 times with water, dry to moisture lower than 2% and get final product for 40 DEG C.
Embodiment 3:
A production for enrofloxacin cladding macromolecule taste masking skeleton microgranule, comprises with step:
(1) get 1g enrofloxacin and 1g stearic acid, add in 5ml dichloromethane, by magnetic stirrer, make it to dissolve, become solution A;
(2) 0.5g sodium lauryl sulphate is dissolved in 50ml purified water, becomes solution B;
(3) solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 35 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-Stearic acid solids dispersion;
(4) get 0.75g sodium alginate and be dissolved in containing in the suspension solution of enrofloxacin-Stearic acid solids dispersion in step (3), become solution C;
(5) get 0.9g chitosan and 30g calcium chloride is dissolved in 300ml water, become solution D;
(6) solution C is added dropwise in solution D, after solidification 5min, filters, wash 3 times with water, dry to moisture lower than 2% and get final product for 40 DEG C.
By following test, effect of the present invention is described in detail:
Test 1, oral cavity dissolution test:
For investigating the taste masking effect of enrofloxacin cladding macromolecule taste masking skeleton microgranule of the present invention, by Fusayama-Meyer artificial saliva solution formula preparation Mouthsimulator solution, get enrofloxacin cladding macromolecule taste masking skeleton microgranule 50mg at every turn and stir 30s by 60r/min speed in the Mouthsimulator solution of 10ml (37 ± 0.5) DEG C, get filter solution and survey its oral cavity release, the results are shown in Table 1.The oral cavity release of enrofloxacin cladding macromolecule taste masking skeleton microgranule of the present invention is all less than the bitter threshold 2 μ g/mL of enrofloxacin to pig as can be seen from Table 1, can play taste masking effect.
The oral cavity release of table 1 enrofloxacin cladding macromolecule taste masking skeleton microgranule
Test 2, clinical taste masking effect expedition:
For the taste masking effect of checking enrofloxacin cladding macromolecule taste masking skeleton microgranule of the present invention on animal clinical, the health pig of 24 15-30kg male and female half and half is selected to make experimental subject, according to the drug loading of enrofloxacin cladding macromolecule taste masking skeleton microgranule, by being equivalent to containing enrofloxacin 10mg/kg mixed feeding, the feed intake of the forward and backward pig of administration is investigated in contrast, the results are shown in Table 2; As can be seen from Table 2, enrofloxacin cladding macromolecule taste masking skeleton microgranule of the present invention without impact, illustrates that the present invention has the effect successfully covering enrofloxacin bitterness on the feed intake of pig.
Table 2 clinical taste masking effect expedition result
Test 3, enrofloxacin cladding macromolecule taste masking skeleton microgranule are in the pharmacokinetics of experimental rabbit:
12 rabbit are divided into two groups, and group 1 is the former medicine group of enrofloxacin, and group 2 is enrofloxacin cladding macromolecule taste masking skeleton microgranule group, and before experiment, rabbit special feed is raised one week, and before administration, every rabbit adopts blank blood once along auricular vein; All take the administration of gavage mode for two groups, dosage is 10mg/kg by enrofloxacin.After administration, respectively at 15,30,45min and 1,1.5,2,3,4,6,8,10,12,24,36,48,60, each ear edge vein exploitating blood of 72h once, take a blood sample 1ml at every turn, heparin sodium anticoagulant, the centrifugal 5min of 3000r/min, gets upper plasma, puts-20 DEG C of refrigerators for subsequent use; To measure the content of enrofloxacin after treated for gained blood plasma extraction medicine with high-efficient solution phase chromatography, the data obtained adopts DAS2.0 pharmacokinetics software to process, with R
2maximum and AIC value minimum principle selects best pharmacokinetic model, calculates the pharmacokinetic parameter of respective data.Blood drug level and dynamic mathematic(al) parameter SPSS (17.0) analyze diversity, the results are shown in Table 3.
The former medicine of table 3 enrofloxacin and the pharmacokinetics partial parameters (n=6) of enrofloxacin cladding macromolecule taste masking skeleton microgranule in rabbit body
Note: A: difference is extremely remarkable, P < 0.01; B: significant difference, P < 0.05; The expression do not indicated is not remarkable, P > 0.05.
As can be seen from Table 3, the peak time (T of former medicine group and high molecular particle group
max), absorption halftime (t
1/2Ka), eliminate half-life (t
1/2 β) and area under the drug-time curve (AUC
0-∞) there is significant difference, result illustrate enrofloxacin be prepared into cladding macromolecule taste masking skeleton microgranule after its absorb, to eliminate comparatively crude drug slow, and absorb completely, cladding macromolecule taste masking skeleton microgranule has obvious slow release effect to enrofloxacin, can improve the bioavailability of enrofloxacin.
The foregoing is only preferred embodiment of the present invention, not in order to limit the present invention, all any amendments done within the spirit and principles in the present invention, equivalent replacement and improvement etc., all should be included within protection scope of the present invention.
Claims (5)
1. an enrofloxacin cladding macromolecule taste masking skeleton microgranule, is characterized in that, described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises enrofloxacin and adjuvant; Described enrofloxacin mass percent is 10-30%, and described adjuvant mass percent is: stearic acid 10% ~ 30%, and stearic acid is glyceryl monostearate or glycerol distearate, chitosan 13.3% ~ 66.7%, sodium alginate 13.3% ~ 26.7%.
2. a preparation method for enrofloxacin cladding macromolecule taste masking skeleton microgranule, is characterized in that, the preparation method of described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises the following steps:
Step one, gets one or both of the stearic acid of the enrofloxacin of 10-30 part and 10-30 part, glycerol distearate or glyceryl monostearate, adds in organic solvent, by magnetic stirrer, make it to dissolve, become solution A;
Step 2, gets emulsifying agent in purified water, and dissolving the amount become containing emulsifying agent is the solution B of 1-3%;
Step 3, solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 35-45 DEG C of temperature, insulated and stirred makes organic solvent be evaporated completely, and must be enclosed with the suspension solution of the solid dispersion of enrofloxacin;
Step 4, the sodium alginate getting 13.3 ~ 26.7 parts is dissolved in containing in the suspension solution of Enrofloxacin solid dispersion in step 3, becomes solution C;
Step 5, the calcium chloride getting the chitosan of 13.3 ~ 66.7 parts and 24-30 part is soluble in water, becomes solution D;
Step 6, is added dropwise to solution C in solution D, after solidification 5-10min, filters, washes 3 times with water, dries to the moisture of microgranule lower than 2.0% and get final product for 40 DEG C.
3. the preparation method of enrofloxacin cladding macromolecule taste masking skeleton microgranule as claimed in claim 2, it is characterized in that, the preparation method of described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises the following steps:
Step one, gets 0.6g enrofloxacin and 1g stearic acid, adds in 5ml dichloromethane, by magnetic stirrer, makes it to dissolve, becomes solution A;
Step 2,0.5g polyvinyl alcohol is dissolved in 50ml purified water, becomes solution B;
Step 3, solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 40 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-Stearic acid solids dispersion;
Step 4, gets 0.75g sodium alginate and is dissolved in containing in the suspension solution of enrofloxacin-Stearic acid solids dispersion in step 3, become solution C;
Step 5, gets 0.45g chitosan and 24g calcium chloride is dissolved in 300ml water, becomes solution D;
Step 6, is added dropwise to solution C in solution D, after solidification 10min, filters, washes 3 times with water, dries to moisture lower than 2% and get final product for 40 DEG C.
4. the preparation method of enrofloxacin cladding macromolecule taste masking skeleton microgranule as claimed in claim 2, it is characterized in that, the preparation method of described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises the following steps:
Step one, gets 0.5g enrofloxacin and 1g glyceryl monostearate, adds in 5ml dichloromethane, by magnetic stirrer, makes it to dissolve, becomes solution A;
Step 2,1g poloxamer is dissolved in 50ml purified water, becomes solution B;
Step 3, solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 38 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-glyceryl monostearate solid dispersion;
Step 4, gets 1g sodium alginate and is dissolved in containing in the suspension solution of enrofloxacin-glyceryl monostearate solid dispersion in step 3, become solution C;
Step 5, gets 0.9g chitosan and 30g calcium chloride is dissolved in 300ml water, becomes solution D;
Step 6, is added dropwise to solution C in solution D, after solidification 8min, filters, washes 3 times with water, dries to moisture lower than 2% and get final product for 40 DEG C.
5. the preparation method of enrofloxacin cladding macromolecule taste masking skeleton microgranule as claimed in claim 2, it is characterized in that, the preparation method of described enrofloxacin cladding macromolecule taste masking skeleton microgranule comprises the following steps:
Step one, gets 1g enrofloxacin and 1g stearic acid, adds in 5ml dichloromethane, by magnetic stirrer, makes it to dissolve, becomes solution A;
Step 2,0.5g sodium lauryl sulphate is dissolved in 50ml purified water, becomes solution B;
Step 3, solution A to be slowly added drop-wise in solution B and under 20 DEG C of conditions Keep agitation, after solution A dropwises completely, be warming up to 35 DEG C, insulated and stirred makes organic solvent be evaporated completely, and obtains the suspension solution containing enrofloxacin-Stearic acid solids dispersion;
Step 4, gets 0.75g sodium alginate and is dissolved in containing in the suspension solution of enrofloxacin-Stearic acid solids dispersion in step 3, become solution C;
Step 5, gets 0.9g chitosan and 30g calcium chloride is dissolved in 300ml water, becomes solution D;
Step 6, is added dropwise to solution C in solution D, after solidification 5min, filters, washes 3 times with water, dries to moisture lower than 2% and get final product for 40 DEG C.
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| CN111821258A (en) * | 2019-04-23 | 2020-10-27 | 河北地邦动物保健科技有限公司 | Compound enrofloxacin oral liquid and preparation method thereof |
| CN111821258B (en) * | 2019-04-23 | 2022-05-03 | 河北地邦动物保健科技有限公司 | Compound enrofloxacin oral liquid and preparation method thereof |
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