CN104586875B - The preparation method of compound tilmicosin enteric coated particles - Google Patents
The preparation method of compound tilmicosin enteric coated particles Download PDFInfo
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Abstract
The invention belongs to veterinary drug technical field, and in particular to a kind of preparation method of compound tilmicosin enteric coated particles, include the steps such as stock, batch mixing, granulation, coating solution preparation, coating successively, wherein, crude granule raw material is：Tilmicosin, colistin, gatifloxacin, sweetener, flavouring agent, bromhexine hydrochloride, oral glucose、Cornstarch, cane sugar powder, dextrin, talcum powder, starch slurry, coating solution raw material are：HPMC, Tween 80, Macrogol 6000, talcum powder, ethanol；The inventive method makes Tilmicosin active ingredient be not destroyed in hydrochloric acid in gastric juice, and can arrive safe and sound intestinal absorption；Gained compound tilmicosin enteric coated particles can prevent and treat the breathing problems such as mycoplasma, pleuropneumonia, swine plague, and can also reduce and have loose bowels, the generation of the bacteriosis such as salmonellosis, can significantly improve the price of deed.
Description
Technical field
The invention belongs to veterinary drug technical field, and in particular to a kind of preparation method of compound tilmicosin enteric coated particles.
Background technology
Tilmicosin is by a kind of semi-synthetic special antibiotic of macrolides livestock and poultry of hydrolysate of tylosin, medicine
With its phosphate.Pharmacokinetics：For oral administration and hypodermic injection absorbs soon, but not exclusively.After taking, apparent distribution solvent is big, lung tissue
In drug concentration it is high；With good tissue penetration, breast, newborn drug concentration fully can be entered from blood rapidly
It is higher, length of holding time, breast in long half time up to 1~2 day.Pharmacological action：To gram-positive bacteria, some Gram-negatives
Bacterium, mycoplasma, conveyor screw etc. have inhibitory action；Have to pleuropneumonia actinomyces, Pasteurella more stronger than tylosin
Antibacterial activity.
Tilmicosin is succeeded in developing in the eighties by Elanco animal healths company of Britain, because of its special antibacterial activity
It is special and characteristics of pharmacokinetics, the medicine have gone through to be clinically used for the preventing and treating of the animal infectious diseases such as ox, goat, sheep, pig, chicken
It is not livestock and birds respiratory disease, such as domestic animal Actinobacillus property pleuropneumonia, pasteurellosis and gallisepticum chicken disease and lactation are moved
The treatment of thing mammitis.Clinical practice：By Tilmicosin for preventing and treating livestock and poultry pneumonia and mammitis etc. on veterinary clinic
During disease, 10~20mg/Kg is subcutaneously injected, can once obtain good efficacy；Can when preventing and treating swine mycoplasma pneumonia
Take 200~400mg/Kg spices that the mode of 15 days is administered, poultry is often used in conjunction 5 days by 100~200mg/Kg drinking-water, can prevent and
Mycoplasma is treated, but is not used in laying hen.The definite curative effect of Tilmicosin treatment mammitis is still to be tested, it is generally understood that
Irrigated 300mg/ times in the subendothelial injection 10mg/Kg of milk cow dry breast phase or breast, can preferably mitigate symptom and suppress pathogenic bacteria
Growth, breeding, play control action.However, drug administration by injection is unsuitable for the administration of pig colony, thus more using administration for oral administration as
It is main, and Tilmicosin is unstable in hydrochloric acid in gastric juice, bioavilability is low, and it is bad generally to mix the effect of medicine is administered.
The content of the invention
In view of the above-mentioned problems, the present invention provides a kind of preparation method of compound tilmicosin enteric coated particles, make Tilmicosin
Active ingredient is not destroyed in hydrochloric acid in gastric juice, and can arrive safe and sound intestinal absorption；Gained compound tilmicosin enteric coated particles can prevent and treat branch
The breathing problems such as substance, pleuropneumonia, swine plague, and can also reduce and have loose bowels, the hair of the bacteriosis such as salmonellosis
It is raw, the price of deed can be significantly improved.
The present invention is achieved through the following technical solutions：
A kind of preparation method of Tilmicosin enteric coated granule is designed, is comprised the following steps：
（1）Crude granule is stocked up by following weight proportion：16~24 parts of Tilmicosin, 16~24 parts of colistin, gatifloxacin
45~55 parts, 8~12 parts of sweetener, 4~6 parts of flavouring agent, 5~8 parts of bromhexine hydrochloride, 50~60 parts of oral glucose、Corn
170~210 parts of starch, 90~110 parts of cane sugar powder, 35~45 parts of dextrin, 2~4 parts of talcum powder, 70~100 parts of starch slurry；
（2）Batch mixing：Take the standby Tilmicosin of institute, colistin, gatifloxacin, sweetener, flavouring agent to be well mixed, add salt
Sour bromhexine, oral glucose are well mixed, and are then added talcum powder, cornstarch, cane sugar powder, dextrin and are well mixed, cross 60
~80 mesh sieves；
（3）Granulation：The standby starch slurry 10~15min of softwood of institute is added, is pelletized after 14~16 mesh sieves, then in 60~65
DEG C drying, by water content control in 1~3wt%, 14 mesh sieve whole grains are crossed after drying, produce crude granule；
（4）Coating solution is stocked up by following weight proportion：HPMC（Hydroxypropyl methyl cellulose）9~13 parts, Tween-80 1~
3 parts, 1~3 part of Macrogol 6000,3~7 parts of talcum powder, 170~230 parts of ethanol；
（5）It is prepared by coating solution：The standby HPMC of institute is placed in container, the standby ethanol of institute is added and stirs 1 hour, add and tell
Temperature -80, Macrogol 6000, talcum powder are well mixed, and then make uniform liquid with colloid mill defibrination or stirring, are made
It is standby for coating solution；
（6）Coating：Seed-coating machine is preheated, by step（3）Crude granule after sieving whole grain is placed in seed-coating machine, and by crude granule
50~60 DEG C are preheated to, then starts Liquid spraying pump, coating solution is sprayed into the particle surface rotated with tangential direction, until being coated
Into rear closing Liquid spraying pump, 45~55 DEG C are continued to dry 30min, are then cooled to normal temperature, are produced Tilmicosin enteric coated granule.
Preferably, step（1）Crude granule is stocked up by following weight proportion：20 parts of Tilmicosin, 20 parts of colistin, add for sand
50 parts of star, 10 parts of sweetener, 5 parts of flavouring agent, 6 parts of bromhexine hydrochloride, 55 parts of oral glucose、190 parts of cornstarch, cane sugar powder
100 parts, DEXTRIN part, 3 parts of talcum powder, 85 parts of starch slurry.
Preferably, step（4）Coating solution is stocked up by following weight proportion：11 parts of HPMC, 2 parts of Tween-80, polyethylene glycol
6000 2 parts, 5 parts of talcum powder, 200 parts of ethanol.
Preferably, the sweetener is stevioside、D-sorbite, mannitol, maltitol, xylitol saccharin, saccharin
At least one of sodium, honey element, Aspartame, acesulfame potassium；The flavouring agent be Ethyl vanillin, natural perfume material extract,
At least one of ethylmaltol, isoamyl acetate, ethyl butyrate.
Preferably, step（3）The water of convention amount is added during the softwood processed.
Preferably, the content of starch of the starch slurry is 15wt%.
Preferably, in the coating process, the mass ratio of crude granule and coating solution is 10：1.
Preferably, in the seed-coating machine warm, leaving air temp is 70 DEG C.
Preferably, in the coating process, 15~25Hz of speed of seed-coating machine, hydrojet 3~8Hz of frequency, blower fan frequency
15~28Hz of rate, 40~45 DEG C of coating solution temperature.
Development test shows that bromhexine hydrochloride used has relatively dissolving mucus effect by force, can make the mucopolysaccharide in pig phlegm
Fibrous fracture, mucopolysaccharide decompose, and desaturation sputum, may also suppress the synthesis of mucopolysaccharide, reduce sialic acid in phlegm（Acid mucopolysaccharide into
/ mono-）Content, phlegm viscosity is reduced, facilitate medicine to enter internal.Simultaneously, moreover it is possible to promote the ciliary movement of respiratory mucosa, have
There are nauseous phlegm-dispelling functions, sputum is easy to expectoration, keep respiratory smooth.What is more important, in the present invention with for rice
Examine star, gatifloxacin shares, have synergy, antibacterial curative effect can be increased.
The positive beneficial effect of the present invention：
（1）The inventive method makes Tilmicosin active ingredient be not destroyed in hydrochloric acid in gastric juice, and can arrive safe and sound intestinal absorption；Institute
The breathing problems such as mycoplasma, pleuropneumonia, swine plague can be prevented and treated by obtaining compound tilmicosin enteric coated particles, and can also reduce drawing
The generation of the bacteriosises such as dilute, salmonellosis, the price of deed can be significantly improved.
（2）Gained compound tilmicosin of the invention is not only effective to positive bacteria, mycoplasma infection, and to negative microbial infections
Effectively；Available for treatment bacterium, mycoplasma respiratory tract infection, it may also be used for bacillary enteron aisle disease.
（3）The inventive method masks the bitter taste of medicine, improves palatability.
Points for attention：Gained compound tilmicosin enteric coated particles of the invention should not be with Florfenicol, clindamycin with use.
Application method：Health care/prevention：250g/ ton material+300g Amoxicillins/ton material；Treatment：500g/ ton material；
Positioning：1. prevention, treatment porcine mycoplasmal pneumonia, contagious pleuropneumonia, swine plague, haemophilus suis disease etc..2.
Pig bacterial enteritis, have loose bowels.
Embodiment
Illustrate the embodiment of the present invention with reference to specific embodiment, but following examples are used only in detail
Illustrate the present invention, the scope not limiting the invention in any way.
Embodiment 1
A kind of preparation method of compound tilmicosin enteric coated particles, comprises the following steps：
（1）Crude granule is stocked up by following weight proportion：20 parts of Tilmicosin, 20 parts of colistin, 50 parts of gatifloxacin, sweet taste
10 parts of agent, 5 parts of flavouring agent, 6 parts of bromhexine hydrochloride, 55 parts of oral glucose、190 parts of cornstarch, 100 parts of cane sugar powder, dextrin
40 parts, 3 parts of talcum powder, 85 parts of starch slurry；
（2）Batch mixing：Take the standby Tilmicosin of institute, colistin, gatifloxacin, sweetener, flavouring agent to be well mixed, add salt
Sour bromhexine, oral glucose are well mixed, and are then added talcum powder, cornstarch, cane sugar powder, dextrin and are well mixed, cross 70
Mesh sieve；
（3）Granulation：The standby starch slurry softwood 12min of institute is added, pelletizes after 15 mesh sieves, then in 63 DEG C of dryings, will contain
Water rate control crosses 14 mesh sieve whole grains after 1~3wt%, drying, produces crude granule；
（4）Coating solution is stocked up by following weight proportion：11 parts of HPMC, 2 parts of Tween-80,2 parts of Macrogol 6000, cunning
5 parts of stone flour, 200 parts of ethanol；
（5）It is prepared by coating solution：The standby HPMC of institute is placed in container, the standby ethanol of institute is added and stirs 1 hour, add and tell
Temperature -80, Macrogol 6000, talcum powder are well mixed, and then make uniform liquid with colloid mill defibrination or stirring, are made
It is standby for coating solution；
（6）Coating：Seed-coating machine is preheated, by step（3）Crude granule after sieving whole grain is placed in seed-coating machine, and by crude granule
50 DEG C are preheated to, then starts Liquid spraying pump, coating solution is sprayed into the particle surface rotated with tangential direction, until after the completion of coating
Liquid spraying pump is closed, 50 DEG C are continued to dry 30min, are then cooled to normal temperature, are produced Tilmicosin enteric coated granule.
Step（3）The water of convention amount is added during the softwood processed.The content of starch of the starch slurry is 15wt%.
In the coating process, the mass ratio of crude granule and coating solution is 10：1.In the seed-coating machine warm, leaving air temp 70
℃.In the coating process, seed-coating machine speed 20Hz, hydrojet frequency 5Hz, blower fan frequency 21Hz, 42 DEG C of coating solution temperature.
Embodiment 2
A kind of preparation method of compound tilmicosin enteric coated particles, comprises the following steps：
（1）Crude granule is stocked up by following weight proportion：16 parts of Tilmicosin, 16 parts of colistin, 45 parts of gatifloxacin, sweet taste
8 parts of agent, 4 parts of flavouring agent, 5 parts of bromhexine hydrochloride, 50 parts of oral glucose、170 parts of cornstarch, 90 parts of cane sugar powder, dextrin 35
Part, 2 parts of talcum powder, 70 parts of starch slurry；
（2）Batch mixing：Take the standby Tilmicosin of institute, colistin, gatifloxacin, sweetener, flavouring agent to be well mixed, add salt
Sour bromhexine, oral glucose are well mixed, and are then added talcum powder, cornstarch, cane sugar powder, dextrin and are well mixed, cross 80
Mesh sieve；
（3）Granulation：The standby starch slurry softwood 10min of institute is added, pelletizes after 14 mesh sieves, then in 60 DEG C of dryings, will contain
Water rate control crosses 14 mesh sieve whole grains after 1~3wt%, drying, produces crude granule；
（4）Coating solution is stocked up by following weight proportion：HPMC（Hydroxypropyl methyl cellulose）13 parts, it is 3 parts of Tween-80, poly-
6,000 3 parts of ethylene glycol, 7 parts of talcum powder, 230 parts of ethanol；
（5）It is prepared by coating solution：The standby HPMC of institute is placed in container, the standby ethanol of institute is added and stirs 1 hour, add and tell
Temperature -80, Macrogol 6000, talcum powder are well mixed, and then make uniform liquid with colloid mill defibrination or stirring, are made
It is standby for coating solution；
（6）Coating：Seed-coating machine is preheated, by step（3）Crude granule after sieving whole grain is placed in seed-coating machine, and by crude granule
60 DEG C are preheated to, then starts Liquid spraying pump, coating solution is sprayed into the particle surface rotated with tangential direction, until after the completion of coating
Liquid spraying pump is closed, 55 DEG C are continued to dry 30min, are then cooled to normal temperature, are produced Tilmicosin enteric coated granule.
Step（3）The water of convention amount is added during the softwood processed.The content of starch of the starch slurry is 15wt%.
In the coating process, the mass ratio of crude granule and coating solution is 10：1.In the seed-coating machine warm, leaving air temp 70
℃.In the coating process, seed-coating machine speed 15Hz, hydrojet frequency 3Hz, blower fan frequency 15Hz, 40 DEG C of coating solution temperature.
Embodiment 3
A kind of preparation method of compound tilmicosin enteric coated particles, comprises the following steps：
（1）Crude granule is stocked up by following weight proportion：24 parts of Tilmicosin, 24 parts of colistin, 55 parts of gatifloxacin, sweet taste
12 parts of agent, 6 parts of flavouring agent, 8 parts of bromhexine hydrochloride, 60 parts of oral glucose、210 parts of cornstarch, 110 parts of cane sugar powder, dextrin
45 parts, 4 parts of talcum powder, 100 parts of starch slurry；
（2）Batch mixing：Take the standby Tilmicosin of institute, colistin, gatifloxacin, sweetener, flavouring agent to be well mixed, add salt
Sour bromhexine, oral glucose are well mixed, and are then added talcum powder, cornstarch, cane sugar powder, dextrin and are well mixed, cross 60
Mesh sieve；
（3）Granulation：The standby starch slurry softwood 15min of institute is added, pelletizes after 16 mesh sieves, then in 65 DEG C of dryings, will contain
Water rate control crosses 14 mesh sieve whole grains after 1~3wt%, drying, produces crude granule；
（4）Coating solution is stocked up by following weight proportion：HPMC（Hydroxypropyl methyl cellulose）9 parts, it is 1 part of Tween-80, poly-
6,000 1 parts of ethylene glycol, 3 parts of talcum powder, 170 parts of ethanol；
（5）It is prepared by coating solution：The standby HPMC of institute is placed in container, the standby ethanol of institute is added and stirs 1 hour, add and tell
Temperature -80, Macrogol 6000, talcum powder are well mixed, and then make uniform liquid with colloid mill defibrination or stirring, are made
It is standby for coating solution；
（6）Coating：Seed-coating machine is preheated, by step（3）Crude granule after sieving whole grain is placed in seed-coating machine, and by crude granule
50 DEG C are preheated to, then starts Liquid spraying pump, coating solution is sprayed into the particle surface rotated with tangential direction, until after the completion of coating
Liquid spraying pump is closed, 45 DEG C are continued to dry 30min, are then cooled to normal temperature, are produced Tilmicosin enteric coated granule.
Step（3）The water of convention amount is added during the softwood processed.The content of starch of the starch slurry is 15wt%.
In the coating process, the mass ratio of crude granule and coating solution is 10：1.In the seed-coating machine warm, leaving air temp 70
℃.In the coating process, seed-coating machine speed 25Hz, hydrojet frequency 8Hz, blower fan frequency 28Hz, coating solution temperature 45 C.
First, pig farm is tested
1. test method：
On pig farm, once find Tong Chang, with there are the breathing problems such as mycoplasma, pleuropneumonia, swine plague in the swinery on column
Or have loose bowels, the bacteriosis such as salmonellosis is individually or during mixed infection, will appear from immediately the pigs of clinical symptoms with not yet
Show the hypothesis health pig isolation of clinical symptoms.Pair assume health pig admix the embodiment of the present invention 1 by every 1000 kg diet
Gained compound tilmicosin enteric coated particles 250g+ Amoxicillin 300g, are fully mixed thoroughly, are even fed 4~5 days.To there are clinical symptoms
Pig, admix the gained compound tilmicosin enteric coated particles 500g of the embodiment of the present invention 1 by every 1000 kg diet, fully mix thoroughly,
Even feed 4~5 days.
2. efficacy determination：
The daily early, middle and late clinical symptoms for examining pig after medication, whether the hypothesis health pig particularly in swinery
There are clinical symptoms, be divided into according to therapeutic effect effective and invalid.After medication 6 days, the pig symptom for clinical symptoms occurred is complete
Disappear, or original same group, do not occur clinical symptoms with the hypothesis health pig in field, or there is no new sick pig being discontinued in 15 days
Occur, be determined as effectively.6 days after medication, the pig for occurring clinical symptoms originally still has obvious clinical symptoms or death, after drug withdrawal
Recurred again in 15 days, originally Symptomatic hypothesis health pig performance clinical symptoms person, is invalid.
3. test effect：
In January, 2014 in October, 2014, pig gas is treated with the gained compound tilmicosin enteric coated particles of the embodiment of the present invention 1
Asthma disease, treats same group and the pig 2570 of clinical symptoms occurs, effective 2503, effective percentage 97.4%；Prevention is the same as group's not yet table
The hypothesis health pig 1104 of existing clinical symptoms, effective 1092, effective percentage 98.9%.With the gained compound of the embodiment of the present invention 1
Tilmicosin enteric coated granule prevents and treats swine plague, and treating same group pig has the pig 1084 of clinical symptoms, effective 1002, efficient
92.4%；Prevention with group assume health pig 1580, effective 1492, effective percentage 94.4%.It is multiple with the gained of the embodiment of the present invention 1
Square Tilmicosin enteric coated granule prevents and treats porcine contagious pleuropneumonia, treats same group and the pig 3298 of clinical symptoms occurs, effectively
3181, effective percentage 96.5%；Prevention not yet shows the hypothesis health pig 4180 of clinical symptoms with group, effective 4101, has
Efficiency 98.1%.With the gained compound tilmicosin enteric coated particles of the embodiment of the present invention 1 preventing and treating swine enzootic pneumonia, swine plague, pleura lung
Scorching Actinobacillus mixed infection, treat same group and the pig 2170 of clinical symptoms occur, effective 2079, effective percentage 95.8%；In advance
The anti-hypothesis health pig 2341 that clinical symptoms are not yet showed with group, effective 2286, effective percentage 97.7%.
2nd, model case contrast test
1. the pig on the small-sized pig farm in Jiyuan, Henan city by immune programme for children carry out swine fever, blue otopathy immunity inoculation, 2014
Year January, there is cough, asthma in 104 market pigs of the body weight on 35~45 kilograms of 10 columns in same field, panted sooner or later or feed
Shi Mingxian, coughed in continuity, body temperature, appetite are without significant changes.Cut open inspection both sides lungs, lobus cardiacus, sharp leaf and lobus diaphragmaticus are red in light ash
Color, hardness increase, for outward appearance like pancreas sample, tentative diagnosis is swine enzootic pneumonia, and 104 pigs are divided into two groups at random in units of column,
That is the gained compound tilmicosin enteric coated particles group of the embodiment of the present invention 1 and common Tilmicosin pre-mixing agent group.The gained of embodiment 1 is multiple
Square Tilmicosin enteric coated granule group 54, Tilmicosin enteric coated granule is added in basal diet by 500g/ ton material, is even fed 5 days；
Common Tilmicosin group 50, by specification dosage add common Tilmicosin pre-mixing agent in basal diet, even fed 7 days.
Result of the test：The efficient gained compound tilmicosin enteric coated particles group of the embodiment of the present invention 1 is 100%（54/54）,
And common Tilmicosin pre-mixing agent group efficient only 60%（30/50）.Effective percentage difference 40%, difference is extremely notable（P<
0.01）.
2. the middle pig in 48,6 column is supported by Henan Tanghe County Yuan Tan towns household that raises a large number of pigs, in September, 2014 has the part pig to be in clinically
Existing body temperature rise, cough, foam sample liquid body is flowed out from mouth, nose, expiratory dyspnea, in sitting position of dog gesture, has inflammation in neck, bottleneck throat
Property swelling, skin has red small blutpunkte, and mucous membrane is in bluish violet.There is a hydrops in the visible subcutaneous, thoracic cavity of cut open inspection, pericardium, the heart, liver,
Spleen, kidney, lung and lymph node have bleeding, and lung section is in marble sample, and tentative diagnosis is swine plague.Before this experiment is carried out,
Dead 3.45 pigs of surviving are randomly divided into two groups, i.e. the gained compound tilmicosin enteric coated particles group of embodiment 1 and often
Advise antibacterials group.The gained compound tilmicosin enteric coated particles group 25 of embodiment 1（Wherein occur 11 of clinical symptoms）,
The addition gained compound tilmicosin enteric coated particles 500g/ ton material of embodiment 1 in the feed of any antibiotic additive are not contained, even
Feed 5 days；Conventional antimicrobial medicine group 20（Wherein occur 5 of clinical symptoms）, Amoxicillin, sulfonamides are added in daily ration
The pulvis such as thing and Ciprofloxacin.
Result of the test：The gained compound tilmicosin enteric coated particles group of embodiment 1 cures 10 to there is clinical pig, has
Efficiency 90.9% (10/11)；Not yet show effective 14 of the prevention of clinical symptoms, effective percentage 100%（14/14）.And conventional antimicrobial
Medicine group, the effective percentage for clinical symptoms occur are only 3, effective percentage 60%（3/5）, the prevention effective 10 of clinical symptoms is not presented
Head, effective percentage 66.7%（10/15）.
3. 2 months 2014, the growing and fattening pigs of 162, Jiangxi camphor tree pig farm have part pig body temperature rise, in sitting position of dog gesture,
Abdominal respiration, nose are bled liquid and mucus, and skin, ear are blue, and dead 12, cut open inspection thoracic cavity is visible fibrinous exudate,
Blood clotting is bad, and thoracic cavity, lung and pleura and the extensive adhesion of diaphram, tentative diagnosis are porcine contagious pleuropneumonia.Surviving
150 pigs be randomly divided into 2 groups.That is the gained compound tilmicosin enteric coated particles group of embodiment 1 and conventional Tilmicosin premix
Agent group.Tilmicosin enteric coated granule group totally 80（Wherein there are clinical symptoms 48）, it is real by being added in every 1000 kg. ration
The gained compound tilmicosin enteric coated particles 500g of example 1 is applied, is even fed 5 days；Conventional Tilmicosin pre-mixing agent group totally 70（Wherein have and face
36 of bed symptom）, by 1000g is added in every 1000 kg. ration, even feed 7 days.
Result of the test：The gained compound tilmicosin enteric coated particles group of embodiment 1 has to there is the healing 46 of clinical symptoms
Efficiency 95.8%（46/48）, it is assumed that health pig does not have new case to occur, prevention effective percentage 100%（32/32）.And routine replaces rice
Star pre-mixing agent group is examined to there is the pig of clinical symptoms, dead 8 during medication, cures 28, effective percentage is only 77.7%（28/
36）；The pig of clinical symptoms is not yet showed, there are 8 clinical symptoms occur again during being prevented with Tilmicosin pre-mixing agent（It is wherein dead
2）, effective 26 of prevention, effective percentage 76.5%（26/34）.The gained compound tilmicosin enteric coated particles group of embodiment 1 is efficient
It is efficient than conventional Tilmicosin pre-mixing agent group difference high by 18.1% and 23.5%, the extremely notable P of difference with prevention<0.01.
3rd, brief summary and discussion
1. gained compound tilmicosin enteric coated particles of the invention have higher antibacterial activity than conventional Tilmicosin pre-mixing agent,
The porcine respiratory disease triggered with its preventing and treating by pathogen, into after body, blood concentration is high, absorbs fast, length of holding time, tool
There is powerful suppression and kill bacterium.Currently swine enzootic pneumonia, swine plague, porcine contagious pleuropneumonia etc. is prevented and treated with it to exhale
Inhale road disease effect and be better than Tilmicosin pre-mixing agent and other antibacterials.
2. pass through clinical practice in this year, it was demonstrated that pig farm is with compound tilmicosin enteric coated particles of the present invention in swinery
Swine enzootic pneumonia, swine plague, the porcine contagious pleuropneumonia for clinical symptoms or subclinical infection occur have good treatment and prevention
Effect.And there is few dosage, saving medication expense, reduce the advantages of labor intensity.
3. bad environmental condition is the main reason for porcine respiratory disease occurs, therefore, in the compound obtained by the present invention
While Tilmicosin enteric coated granule is prevented and treated, to strengthen feeding management, periodically carry out disinfection, will be by immune programme for children after sick pig rehabilitation
Carry out various epidemic diseases（Bacterium）The immunity inoculation of seedling, it can just give full play to the therapeutic action of medicine.
The invention is not limited in above-mentioned embodiment, those skilled in the art can also make a variety of changes accordingly,
It is but any all to cover within the scope of the claims with equivalent or similar change of the invention.
Claims (7)
1. a kind of preparation method of compound tilmicosin enteric coated particles, it is characterised in that comprise the following steps：
（1）Crude granule is stocked up by following weight proportion：16~24 parts of Tilmicosin, 16~24 parts of colistin, gatifloxacin 45~
55 parts, 8~12 parts of sweetener, 4~6 parts of flavouring agent, 5~8 parts of bromhexine hydrochloride, 50~60 parts of oral glucose、Cornstarch
170~210 parts, 90~110 parts of cane sugar powder, 35~45 parts of dextrin, 2~4 parts of talcum powder, 70~100 parts of starch slurry；
（2）Batch mixing：Take the standby Tilmicosin of institute, colistin, gatifloxacin, sweetener, flavouring agent to be well mixed, add hydrochloric acid bromine
Newly, oral glucose be well mixed, then add talcum powder, cornstarch, cane sugar powder, dextrin are well mixed, cross 60~80
Mesh sieve；
（3）Granulation：The standby starch slurry 10~15min of softwood of institute is added, is pelletized after 14~16 mesh sieves, it is then dry in 60~65 DEG C
It is dry, water content control is crossed into 14 mesh sieve whole grains after 1~3wt%, drying, produces crude granule；
（4）Coating solution is stocked up by following weight proportion：9~13 parts of HPMC, 1~3 part of Tween-80, Macrogol 6000 1~3
Part, 3~7 parts of talcum powder, 170~230 parts of ethanol；
（5）It is prepared by coating solution：The standby HPMC of institute is placed in container, the standby ethanol of institute is added and stirs 1 hour, add Tween-80,
Macrogol 6000, talcum powder are well mixed, and then uniform liquid are made with colloid mill defibrination or stirring, as coating
Liquid is standby；
（6）Coating：Seed-coating machine is preheated, by step（3）Crude granule after sieving whole grain is placed in seed-coating machine, and crude granule is preheated
To 50~60 DEG C, then start Liquid spraying pump, coating solution is sprayed into the particle surface rotated with tangential direction, until after the completion of coating
Liquid spraying pump is closed, 45~55 DEG C are continued to dry 30min, are then cooled to normal temperature, are produced Tilmicosin enteric coated granule；The coating
During, the mass ratio of crude granule and coating solution is 10：1；In the seed-coating machine warm, leaving air temp is 70 DEG C.
2. preparation method according to claim 1, it is characterised in that：Step（1）Crude granule is stocked up by following weight proportion：
It is 20 parts of Tilmicosin, 20 parts of colistin, 50 parts of gatifloxacin, 10 parts of sweetener, 5 parts of flavouring agent, 6 parts of bromhexine hydrochloride, oral
55 parts of glucose、190 parts of cornstarch, 100 parts of cane sugar powder, DEXTRIN part, 3 parts of talcum powder, 85 parts of starch slurry.
3. preparation method according to claim 1, it is characterised in that：Step（4）Coating solution is stocked up by following weight proportion：
11 parts of HPMC, 2 parts of Tween-80,2 parts of Macrogol 6000,5 parts of talcum powder, 200 parts of ethanol.
4. preparation method according to claim 1, it is characterised in that：The sweetener is stevioside、D-sorbite, sweet dew
At least one of sugar alcohol, maltitol, xylitol saccharin, saccharin sodium, honey element, Aspartame, acesulfame potassium；The flavouring agent
For at least one of Ethyl vanillin, natural perfume material extract, ethylmaltol, isoamyl acetate, ethyl butyrate.
5. preparation method according to claim 1, it is characterised in that：Step（3）To be added during the softwood processed often
The water of rule amount.
6. preparation method according to claim 1, it is characterised in that：The content of starch of the starch slurry is 15wt%.
7. preparation method according to claim 1, it is characterised in that：In the coating process, the speed of seed-coating machine
15~25Hz, hydrojet 3~8Hz of frequency, blower fan 15~28Hz of frequency, 40~45 DEG C of coating solution temperature.
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| CN104940147B (en) * | 2015-06-29 | 2018-06-19 | 湖南泰谷生物科技股份有限公司 | A kind of Tilmicosin pre-mixing agent and preparation method thereof |
| CN111166719A (en) * | 2019-12-31 | 2020-05-19 | 郑州都灵兽药科技有限公司 | Preparation method of tulathromycin enteric-coated granules |
| CN116172952A (en) * | 2023-04-21 | 2023-05-30 | 浙江大学 | Tilmicosin xylitol compound injection and preparation method thereof |
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| CN102068412A (en) * | 2011-01-21 | 2011-05-25 | 黑龙江大学 | Enteric targeted tilmicosin particles and preparation method thereof |
| CN103622919A (en) * | 2013-11-14 | 2014-03-12 | 湖北龙翔药业有限公司 | Tilmicosin phosphate enteric granules and preparation method thereof |
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