CN104473879A - Enrofloxacin pellet and preparation method thereof - Google Patents

Abstract

The invention provides an enrofloxacin pellet, which is prepared by wrapping a pellet core with an enteric coating, wherein the pellet core is prepared from enrofloxacin, insect wax, microcrystalline cellulose and starch; the ratio of the insect wax to the enrofloxacin is (1-1.5) to 1; the ratio of the enrofloxacin to the microcrystalline cellulose or starch is (10-15) to (1-2); an enteric coating agent is acrylic resin III, ethylcellulose and cellulose acetate; and the weight percentage of the enteric coating agent in the overall pellet is 5%-10%. According to the pellet disclosed by the invention, the taste can be covered by water-fed suspended enrofloxacin, so that the enrofloxacin can be relatively well applied to animals with sensitive taste; the functional auxiliary material insect wax also has the effect of protecting intestinal tracts, so that the irritation of the enrofloxacin can be reduced, and the application range and the medicine effect of the enrofloxacin are increased.

Description

A kind of enrofloxacin micropill and preparation method thereof

Technical field

The present invention relates to a kind of enrofloxacin micropill.

Background technology

Enrofloxacin (Enrofloxacin) is the fluoroquinolones of first animal specific in the world, there is the features such as has a broad antifungal spectrum, bactericidal activity is strong, distribution in vivo is extensive, good effect is obtained in prevention and therapy animal bacteria epidemic disease and mycoplasma infection, a kind of off-white color or micro-yellow crystalline needle powder, fusing point 221-226 DEG C, odorless.Conventional its hydrochlorate, lactate, sodium salt.These product dissolve under acid or alkaline conditions, slightly molten in dimethyl formamide, chloroform, and slightly soluble in methanol is insoluble in water.The long-time illumination color and luster of these product is deepened.In the place storage that relative humidity is higher, easy moisture absorption caking.Enrofloxacin, as third generation animal specific fluoroquinolones broad spectrum antibiotic, all has good inhibitory or killing effect to resting stage and trophophase antibacterial, respiratory tract and intestinal tract disease choice drug.For preventing and treating secondary and the mixed infection of the viral disease such as multisystemic exhaustion syndrome (PMWS), hyperpyrexia disease, reproductive and respiratory syndrome, circovirus disease, flu after Haemophilus parasuis, mycoplasma, pleuropneumonia, colibacillosis, actinobascillosis, Bacillus pasteurii disease, streptococcicosis, respiratory syndrome (PRDC), weaned piglet.Due to broad spectrum antibacterial and unique bactericidal mechanism of enrofloxacin, it has important effect in pig epidemic prevention and control.But because the dosage form of traditional enrofloxacin is extensive, abused in a large number especially at veterinary clinic, cause the effect of enrofloxacin to be not equal to before; Be the generation due to drug resistance on the one hand, be the tolerance due to animal body itself on the other hand, the bitterness of enrofloxacin self in addition, makes its application more limit to.Therefore, improve the quality of enrofloxacin dosage form, promote that the reasonable employment of enrofloxacin is that protection enrofloxacin can permanently effective guarantee of serving aquaculture.Traditional enrofloxacin oral formulations has powder and a small amount of bag by preparation, powder due to its palatability poor, use less.A small amount of rough bag cannot be ensured to wrap quilt completely by a lot of veterinary drug producer of preparation, causes the refusing to eat of pig.In addition, when pig is bitten into pieces bag by granule once in a while, also can produce bitterness, cause pig refusing to eat.Product granulating coated after coating materials directly mixes with enrofloxacin by the producer particularly had, cannot eliminate the irritating bitterness of enrofloxacin, pig can direct refusing to eat at all.Adopt ordinary coating agent in addition, dissolve in water.Common coating material is all water miscible, can dissolve in snoot or in stomach, if or drink water in material feeding limit, pig limit time, coating materials can dissolve in the mouth, the strong bitterness of release enrofloxacin, if adopt wet feed when feeding, also capsulating material can be dissolved.Therefore the enrofloxacin of this type of bag quilt, when adopting wet feed to feed, meeting refusing to eat, also can dissolve because of some drugs when feeding siccative, causing pig refusing to eat or decline of searching for food in pig oral cavity.In addition, medicine dissolving in Gaster Sus domestica can cause the regurgitation of pig, the symptoms such as vomiting.

Summary of the invention

Technical scheme of the present invention there is provided a kind of enrofloxacin micropill.Another technical scheme of the present invention there is provided the preparation method of this micropill.

A kind of enrofloxacin micropill of the present invention, it is prepared into the ball heart by enrofloxacin and insect wax, microcrystalline Cellulose, starch, then be prepared from by enteric coating, wherein, the ratio of insect wax and enrofloxacin is 1-1.5:1, and the ratio of enrofloxacin and microcrystalline Cellulose or starch is 10-15:1-2; Described enteric coating agents is acrylic resin III, ethyl cellulose, cellulose acetate; The percentage by weight that coating materials accounts for whole micropill is 5-10%.

Wherein, the ratio of insect wax and enrofloxacin is 1.2:1, and the ratio of enrofloxacin and microcrystalline Cellulose or starch is 12:1.

Wherein, described enteric coating agents is acrylic resin III.

The percentage by weight that coating materials accounts for whole micropill is 8%.

Present invention also offers a kind of preparation method preparing described enrofloxacin micropill, it is characterized in that: it comprises the steps:

A, take supplementary material;

B, preparation containing the pill heart:

Let cool after insect wax melting, after adding enrofloxacin and microcrystalline Cellulose or starch mixing, extruded 50 mesh sieves, and then put into spheronizator round as a ball, 30 DEG C of dryings let cool, and choose the ball heart of micropill as next step of 40-50 mesh sieve scope;

C, taste masking enteric coating:

Use coating materials to carry out enteric coating, 20 parts of coating materials are joined after dissolving in 95% ethanol and add Pulvis Talci 4-6 parts, Macrogol 600 2 parts, prepare coating solution; Then the ball heart is put into fluid bed pallet, use coating solution to carry out coating to the ball heart, choose 30-35 object micropill, obtain micropill of the present invention.

Because pig has chewing when eating feedstuff; inventor finds that pig does not have chewing substantially when drinking-water; therefore have developed a kind of by the suspension enrofloxacin odor-masking pellet of throwing something and feeding of drinking water; make enrofloxacin can better be used for sense of taste Sensitivity animal; wherein functional auxiliary material insect wax also has the effect of protection intestinal; the stimulation of enrofloxacin can be reduced, increase range of application and the drug effect of enrofloxacin.

Detailed description of the invention

The preparation of embodiment 1 enrofloxacin micropill of the present invention

1 containing the preparation of the pill heart

Let cool after appropriate insect wax melting, after adding recipe quantity enrofloxacin and appropriate microcrystalline Cellulose (or starch) mixing, extruded 50 mesh sieves, then put into spheronizator round as a ball, 30 DEG C of dryings let cool, and choose the ball heart of micropill as next step of 40-50 mesh sieve scope.Wherein the ratio of insect wax and enrofloxacin is 1-1.5:1, and the ratio of enrofloxacin and microcrystalline Cellulose or starch is 10:1-2.

2 taste masking enteric coatings

Use acrylic resin III to carry out enteric coating, 20g Eudragit Ⅲ is joined after dissolving in the ethanol of 200ml95% and add Pulvis Talci 4--6g, Macrogol 600 2g, prepare coating solution.Then the ball heart is put into fluid bed pallet, use coating solution to carry out coating to the ball heart, finally choose 30-35 object micropill, get product.Its ectomesoderm coating accounts for the 5-10% of whole micropill.Wherein acrylic resin III may also be ethyl cellulose or cellulose acetate, but preferred acrylic resins III.

The suspendability of 3 different prescription micropills measures

3.1 let cool after the melting of 100g insect wax, and after adding 100g enrofloxacin and the mixing of 10g microcrystalline Cellulose, extruded 50 mesh sieves, and then put into spheronizator round as a ball, 30 DEG C of dryings let cool, and choose the ball heart of micropill as next step of 40-50 mesh sieve scope.Use acrylic resin III to carry out enteric coating, 20g Eudragit Ⅲ is joined after dissolving in the ethanol of 200ml95% and add Pulvis Talci 4--6g, Macrogol 600 2g, prepare coating solution.Then the ball heart is put into fluid bed pallet, use coating solution to carry out coating to the ball heart, finally choose 30-35 object micropill, get product, its ectomesoderm coating accounts for 10% of whole micropill, obtains micropill A.

3.2 let cool after the melting of 120g insect wax, and after adding 100g enrofloxacin and the mixing of 10g starch, extruded 50 mesh sieves, and then put into spheronizator round as a ball, 30 DEG C of dryings let cool, and choose the ball heart of micropill as next step of 40-50 mesh sieve scope.Use acrylic resin III to carry out enteric coating, 20g Eudragit Ⅲ is joined after dissolving in the ethanol of 200ml95% and add Pulvis Talci 4--6g, Macrogol 600 2g, prepare coating solution.Then the ball heart is put into fluid bed pallet, use coating solution to carry out coating to the ball heart, finally choose 30-35 object micropill, get product.Its ectomesoderm coating accounts for 8% of whole micropill, obtains micropill B.

3.3 let cool after the melting of 150g insect wax, and after adding 100g enrofloxacin and the mixing of 20g starch, extruded 50 mesh sieves, and then put into spheronizator round as a ball, 30 DEG C of dryings let cool, and choose the ball heart of micropill as next step of 40-50 mesh sieve scope.Use ethyl cellulose to carry out coating to the ball heart, finally choose 30-35 object micropill, get product.Its ectomesoderm coating accounts for 8% of whole micropill, obtains micropill C.

3.4 let cool after the melting of 100g insect wax, and after adding 100g enrofloxacin and the mixing of 15g microcrystalline Cellulose, extruded 50 mesh sieves, and then put into spheronizator round as a ball, 30 DEG C of dryings let cool, and choose the ball heart of micropill as next step of 40-50 mesh sieve scope.Use acrylic resin III to carry out enteric coating, 20g Eudragit Ⅲ is joined after dissolving in the ethanol of 200ml95% and add Pulvis Talci 4--6g, Macrogol 600 2g, prepare coating solution.Then the ball heart is put into fluid bed pallet, use coating solution to carry out coating to the ball heart, finally choose 30-35 object micropill, get product.Its ectomesoderm coating accounts for 5% of whole micropill, obtains micropill D.

3.5 let cool after the melting of 130g insect wax, and after adding 100g enrofloxacin and the mixing of 15g starch, extruded 50 mesh sieves, and then put into spheronizator round as a ball, 30 DEG C of dryings let cool, and choose the ball heart of micropill as next step of 40-50 mesh sieve scope.Use cellulose acetate to carry out coating to the ball heart, finally choose 30-35 object micropill, get product.Its ectomesoderm coating accounts for 8% of whole micropill, obtains micropill E.

The mensuration of 3.6 different prescription suspendabilities

Above-mentioned micropill A, B, C, D are put into 1000ml buchner funnel, after adding 500ml distilled water water, put into the micropill granule releasing oven dry that 50g micropill shake suspension will sink to the bottom respectively at 0.5h, 1h, 2h, 3h, weighed weight, the sedimentation velocity of relatively more each group, the results are shown in Table 1.As can be known from the results, the effect of micropill B is better, and A sedimentation is more, and C is floating more, is unfavorable for using, but it is complete still to advise in two hours, allowing animal drink containing micropill granule medicament.

The sedimentation velocity of the different micropill of table 1 compares

Project	0.5h	1h	2h	3h
					A	25.5g	28.2g	33.4g	35.1g
B	0.4g	0.6g	1.1g	1.8g
					C	3.2g	5.3g	6.1g	7.7g
D	14.4g	16.2g	18.9g	21.2g
					E	2.5g	4.6g	6.0g	6.5g

The mensuration of 4 enrofloxacin vitro releases

4.1 experimental technique

That chooses that B and C micropill carries out simulated gastric fluid and simulated intestinal fluid dissolves performance measurement, getting micropill granule B23g, C27g respectively joins in 1000ml simulated gastric fluid and simulated intestinal fluid, every 10min shake once, observe its melting in simulated gastric fluid and simulated intestinal fluid, and in 1h, 2h, 3h, the content of sampling and measuring wherein enrofloxacin.

The preparation of 4.2 simulated gastric fluids

Get dilute hydrochloric acid 16.4mL, add water 800mL and pepsin 10g, after shaking up, is diluted with water to 1000mL and get final product.

The preparation of 4.3 simulated intestinal fluids

Simulated intestinal fluid: pH7.8 dipotassium hydrogen phosphate 5.59g and potassium dihydrogen phosphate 0.41g, add water melt into 1000mL and get final product.

4.4 measurement result

As known from Table 2, discharge better in intestinal juice with the micropill of acrylic resin III coating, although the ethyl cellulose insoluble material that is water, but be used alone, cause drug release slow, be unfavorable for the performance of drug effect, and the micropill granule of acrylic resin III coating can reach vitro release comparatively stably, discharges also more complete.

Table 2 micropill B, C Release Performance in artificial gastro-intestinal Fluid

Beneficial effect of the present invention is proved below by way of the concrete test of pesticide effectiveness.

Test example 1 micropill of the present invention is to the colibacillary therapeutical effect of meat-type duck

1 experimental program

Choose medium-sized meat-type duck field, Qionglai, this colibacillosis is always relatively more serious, and multiple antibacterials of throwing something and feeding all are difficult to control.The meat-type duck main manifestations of ehec infection for spirit is depressed, dyspnea, have the symptom such as rale and sneeze, airbag wall thickens, muddy, and what have has fiber-like exudate, and with fibrinous pericarditis and peritonitis etc.It is also frequent with pericarditis, perihepatitis that the duck that dies of illness cuts open the visible airsac disease of inspection, once in a while visible septicemia, eyeball inflammation and synovitis etc.The liver of aseptic meat-type duck of taking to die of illness is taken back use for laboratory Mai Kangkai culture medium separation and Culture and is obtained Escherichia coli bacterium colony, is diagnosed as coli-infection.Random selecting meat-type duck 60, be equally divided into 3 groups, often organize 20, be divided into blank group, matched group and experimental group, after weighed weight, drinking-water is thrown something and fed and is converted isodose commercially available enrofloxacin powder and micropill granule B respectively, blank group is not offerd medicine, after 5 days, and weighed weight calculate survival rate respectively.

2 results and discussion

Experimental result, in table 3, has good effect by the control of the known enrofloxacin micropill of result to meat-type duck colibacillosis, and is better than ordinary preparation, while bacterial disease obtains controlling, is conducive to the raising of efficiency of gain.

Table 3 enrofloxacin micropill is to the therapeutic effect of meat-type duck colibacillosis

Claims (5)

1. an enrofloxacin micropill, it is characterized in that: it is prepared into the ball heart by enrofloxacin and insect wax, microcrystalline Cellulose, starch, be prepared from by enteric coating again, wherein, the ratio of insect wax and enrofloxacin is 1-1.5:1, and the ratio of enrofloxacin and microcrystalline Cellulose or starch is 10-15:1-2; Described enteric coating agents is acrylic resin III, ethyl cellulose, cellulose acetate; The percentage by weight that coating materials accounts for whole micropill is 5-10%.

2. enrofloxacin micropill according to claim 1, is characterized in that: the ratio of insect wax and enrofloxacin is 1.2:1, and the ratio of enrofloxacin and microcrystalline Cellulose or starch is 12:1.

3. enrofloxacin micropill according to claim 1, is characterized in that: described enteric coating agents is acrylic resin III.

4. enrofloxacin micropill according to claim 1, is characterized in that: the percentage by weight that coating materials accounts for whole micropill is 8%.

5. prepare a preparation method for the enrofloxacin micropill described in claim 1-4 any one, it is characterized in that: it comprises the steps:

A, take supplementary material;

B, preparation containing the pill heart:

Let cool after insect wax melting, after adding enrofloxacin and microcrystalline Cellulose or starch mixing, extruded 50 mesh sieves, and then put into spheronizator round as a ball, 30 DEG C of dryings let cool, and choose the ball heart of micropill as next step of 40-50 mesh sieve scope;

C, taste masking enteric coating:

Use coating materials to carry out enteric coating, 20 parts of coating materials are joined after dissolving in 95% ethanol and add Pulvis Talci 4-6 parts, Macrogol 600 2 parts, prepare coating solution; Then the ball heart is put into fluid bed pallet, use coating solution to carry out coating to the ball heart, choose 30-35 object micropill, obtain micropill of the present invention.