CN108653230A - Coating type veterinary drug pill and preparation method thereof - Google Patents
Coating type veterinary drug pill and preparation method thereof Download PDFInfo
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- CN108653230A CN108653230A CN201810656720.1A CN201810656720A CN108653230A CN 108653230 A CN108653230 A CN 108653230A CN 201810656720 A CN201810656720 A CN 201810656720A CN 108653230 A CN108653230 A CN 108653230A
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- layer coating
- tilmicosin
- release agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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Abstract
The present invention discloses a kind of coating type veterinary drug pill and preparation method thereof, including following mass fraction than component：Tilmicosin 20 30%, carrier material 39.2 56.5%, internal layer coating sustained release agent 10 12.5%, outer layer coating sustained release agent 10 12.5%, corrigent 0.5 0.8%, texturizers 3 5%；The outer layer coating sustained release agent is the mixture of oil with hydrogenated soybean, the second additive and agar.Tilmicosin pre-mixing agent disclosed by the invention is sustained taste masking and flavoring technology by double-layer coatings; reach to the good masking effect of Tilmicosin bitter taste; it simultaneously can be in intestinal sustained releasing; solve the problems, such as that cultivation terminal spice feeding animals palatability is poor; while improving drug bioavailability, by selection and technological break-through, the limitation of high energy consumption, low output that conventional formulation masking methods are brought is broken; more conducively large-scale production is increased economic efficiency.
Description
Technical field
The invention belongs to field of veterinary medicine preparation, more particularly, to a kind of coating type veterinary drug pill and preparation method thereof.
Background technology
Tilmicosin is a kind of newer macrolides livestock and poultry special antibiotic semi-synthetic by tylosin, is possessed
The special lactone structure of 14-16 membered rings, property is stablized relatively, in antihaemorrhagics pasteurella septica and hemolytic pasteurellaceae
There is stronger effect than tylosin in terms of bacterium.Due to Tilmicosin will not be combined with 80s ribosomes but special combination
50s ribosomal subunits had not only inhibited bacterial peptide chain growth, but also reduced itself toxicity to greatest extent, so Tilmicosin is compared with it
His antibiotic antibacterial activity is strong and comparatively safe, has extremely important effect in terms for the treatment of and preventing livestock and birds respiratory disease.
But Tilmicosin raw material is almost insoluble in water, ordinary preparation product bioavilability is relatively low.There is portion in the market
Point raw materials used phosphate for Tilmicosin of preparation, for oral administration be administered easily are destroyed by hydrochloric acid in gastric juice, can not reach enteron aisle, half-life short,
Degree of being absorbed and utilized is poor.So improved by preparation process, effectively extends drug half-life period in vivo, drug is conveyed to greatest extent
It is the major subjects of current research to heighten the effect of a treatment to targeting moiety.Currently, improving insoluble medicine bioavilability both at home and abroad
Method is more, such as prepares nano-emulsion, dry suspensoid agent, addition hydrotropy and cosolvent, crystal form transformation, but not to bulk pharmaceutical chemicals into
In the case that row processing is to ensure content and drug effect, partly declined in animal body by preparation coating and slow release method with controlling drug
Phase and raising drug availability are still most common way.
But the slow release effect for the medicament that existing coating agent and coating equipment in sugar production line are processed is still poor, and can not be to drug
Absorptivity generate synergistic effect.
Invention content
The present invention for overcome the deficiencies in the prior art, provides a kind of had good sustained release effect, drug is easy to the coating type absorbed
Veterinary drug pill and preparation method thereof.
In order to solve the above-mentioned technical problem, the invention discloses a kind of coating type veterinary drug pills, including following mass fraction
The component of ratio：Tilmicosin 20-30%, carrier material 39.2-56.5%, internal layer coating sustained release agent 10-12.5%, outer layer coating
Sustained release agent 10-12.5%, corrigent 0.5-0.8%, texturizers 3-5%；The outer layer coating sustained release agent is hydrogenated soybean
The mixture of oil, the second additive and agar.
The present invention is sustained taste masking technology by double-layer coatings, has reached to the good masking effect of Tilmicosin bitter taste, solution
The limited problem of Tilmicosin bitter Clinical practice of having determined；Secondly, the stability of drug character is improved, product is non-degradable constant
Color does not lump；Using rilanit special, the differentiation delamination packing clothes of oil with hydrogenated soybean fusing point, then pass through PEG6000, PEG4000
With the texturizers such as microcrystalline cellulose, PVP to the adjustment effect of coatings property；Outer layer coating has by the addition of agar
Effect has achieved the effect that improve animal enterogastric peristalsis, high hence for the absorptivity of drug, medicament bioactivity height；Meanwhile fine jade
Fat can also enhance the immunity of animal, both achieved the purpose that drug is not discharged by taste masking in the oral cavity of animal, stomach, avoided
Common Tilmicosin premix agent formulation the problem of routinely coating taste masking is attended to one thing and lose sight of another, while product can cross stomach in intestinal sustained releasing,
Drug absorption rate is high, and drug bioavailability greatly improves；And it increases to the immunity of animal.
Further, the mass ratio of the oil with hydrogenated soybean, the second additive and agar is 5:1:2-3:1:2.
Further, the internal layer coating sustained release agent includes rilanit special and the first additive, the rilanit special
Mass ratio with the first additive is 8:1-5:1；First additive is one or both of PEG6000 and PEG4000
Combination.
Further, second additive combines for one or both of PEG6000 and PEG4000.
Further, the corrigent is the combination of one or more of saccharin sodium, Aspartame and neotame.
The present invention also provides a kind of preparation methods of coating type veterinary drug pill, it is characterised in that includes the following steps：
A, by the mass fraction percentage weigh respectively Tilmicosin, carrier material, coating slow-release material, corrigent,
Texturizers are spare；
B, Tilmicosin, carrier material and corrigent are uniformly mixed, are first soaked with water in extruder and squeezes granulation, then
Pellet is made by the way that the further ball blast of shot-blasting machine is moulding, the pellet water content control is within 5%；
C, internal layer coating sustained release agent is heated and is melted, texturizers are added and are configured to internal layer coating liquid, temperature is maintained at
80~85 DEG C；
D, the pellet obtained in step b is put into seed-coating machine, Cotton seeds in seed-coating machine is added in internal layer coating buffer
30 minutes blowings are to get head layer coating micro-pill；
E, outer layer coating sustained release agent is heated and is melted, texturizers are added and are configured to outer layer coating liquid, temperature is maintained at
60~65 DEG C；
F, the head layer coating micro-pill obtained in step d is put into seed-coating machine, outer layer coating liquid is added in seed-coating machine
30 minutes blowings of Cotton seeds take -80 mesh of 24 mesh to sieve, by double-layer coatings pellet to get double-layer coatings pellet, screened processing
Size controlling is at 200~800 μm to get finished product.
Further, additive amount of the texturizers in internal layer coated slow release agent is texturizers total amount
40%-70%.
It is sustained taste masking technology by double-layer coatings in the present invention, has been reached to the good masking effect of Tilmicosin bitter taste,
Solve the problems, such as that Tilmicosin bitter Clinical practice is limited；Secondly, the stability of drug character is improved, product is non-degradable not
Discoloration is not lumpd；Using rilanit special, the differentiation delamination packing clothes of oil with hydrogenated soybean fusing point, then by PEG6000,
The texturizers such as PEG4000 and microcrystalline cellulose, PVP to the adjustment effect of coatings property, both reached drug pass through it is dynamic
The purpose that taste masking does not discharge in the oral cavity of object, stomach, avoiding common Tilmicosin premix agent formulation, routinely coating taste masking cares for this mistake
That the problem of, while product can cross stomach in intestinal sustained releasing, drug bioavailability greatly improves；And low energy consumption in preparation process,
Output is high, and industrialization propulsion has a extensive future.
The present invention premixes agent prescription to conventional Tilmicosin on the basis of using for reference former achievements and technique is dashed forward
Broken property is improved, and ingenious matched combined is carried out to conventional material, is all reached in Tilmicosin taste masking, excessively stomach, intestinal sustained releasing etc.
Ideal effect can detect content fully according to national standard, and improved by equipment overcome low yield can limitation,
Product quality and preparation process have a clear superiority.
In conclusion the present invention has the following advantages：It is sustained taste masking and flavoring technology by double-layer coatings, has been reached to replacing
The good masking effect of meter Kao Xing bitter tastes, while it is poor can to solve cultivation terminal spice feeding animals palatability in intestinal sustained releasing
The problem of, while improving drug bioavailability, improve the immunity of drug absorption rate and animal；And pass through selection and skill
Art is broken through, and has broken the limitation of high energy consumption, low output that conventional formulation masking methods are brought, and more conducively large-scale production improves
Economic benefit.
Description of the drawings
Fig. 1 is that hopper placement location figure is tested in contrast test 3；
Fig. 2 is that each sample In Vitro Dissolution experiment gastrointestinal tract release rate compares figure in contrast test 4；
Fig. 3 is that drug-time curve figure is administered orally in 20mg/kg in contrast test 5.
Fig. 4 is the structural schematic diagram of the seed-coating machine in the present invention.
Fig. 5 is the structure sectional view of the heating and stirring tank in the seed-coating machine in the present invention.
Fig. 6 is enlarged drawing at A in Fig. 5.
Fig. 7 is the vertical view of coating pan in the present invention.
Fig. 8 is the cross-sectional view of stirring rod in the present invention.
Specific implementation mode
In order to make those skilled in the art be better understood from the present invention program, below in conjunction in the embodiment of the present invention
Attached drawing, technical solution in the embodiment of the present invention carry out clear, complete description.
Embodiment 1：
A kind of coating type veterinary drug pill, is made of the supplementary material of following masses：
Process：
(1) Tilmicosin 20kg, cornstarch 35kg, maltodextrin are weighed respectively by the mass fraction percentage
15.7kg, rilanit special 10kg, PEG-6000, PEG-4000 each 2kg, oil with hydrogenated soybean 6kg, agar powder 4kg, saccharin sodium
0.8kg, microcrystalline cellulose 3kg, PVPk30 1.5kg, it is spare；
(2) Tilmicosin, cornstarch, maltodextrin and saccharin sodium are uniformly mixed, 2-3kg water is first used in extruder
Wetting squeezes granulation, then pellet is made by the way that the further ball blast of shot-blasting machine is moulding, and the pellet water content control is within 5%；
(3) each 1kg of PEG-6000 and PEG-4000 is taken uniformly to be mixed to get the first additive, by 10kg rilanit specials and
The heating of first additive, which melts and microcrystalline cellulose 2kg, PVPk30 1kg is added stirs evenly, is configured to internal layer coating liquid, temperature
It is maintained at 80~85 DEG C；
(4) pellet obtained in step (2) is put into seed-coating machine, internal layer coating buffer is added in seed-coating machine at coating
30 minutes blowings are managed to get head layer coating micro-pill；
(5) it takes agar powder 4kg that distilled water is added, is heated to agar powder and is completely dissolved, obtain agar solution；PEG- is taken later
Each 1kg of 6000 and PEG-4000 are uniformly mixed and obtain the second additive, and the second additive and oil with hydrogenated soybean 10kg are added together
Simultaneously microcrystalline cellulose 1kg, PVPk30 0.5kg is added in heat fusing, and agar solution is configured to outer layer coating liquid, and temperature is maintained at 60
~65 DEG C；
(6) the head layer coating micro-pill obtained in step (4) is put into seed-coating machine, seed-coating machine is added in outer layer coating liquid
30 minutes blowings of middle Cotton seeds take -80 mesh of 24 mesh to sieve, by double-layer coatings pellet to get double-layer coatings pellet, screened processing
Size controlling at 200~800 μm to get finished product.
As shown in Figure 4-8, specifically, the seed-coating machine includes coating pan 1, hot air apparatus, spraying device and for driving
The first driving motor 11 that the coating pan 1 rotates, the spraying device include heating and stirring tank 2, are connected with the agitator tank 2
Logical conveying pipeline 21, the charging pump 22 on the conveying pipeline 21 and the atomizing lance 23 being connected with the conveying pipeline 21,
The atomizing lance 23 is arranged corresponding to 1 opening of coating pan；Specifically, first driving motor 11 is general motor, institute
The general motor stated is mounted on bearing 12, and the general motor, charging pump 22 and atomizing lance 23 all can be directly from markets
Upper purchase, the structure and operation principle of three are all the prior art, and this will not be repeated here；Made by the setting of heating and stirring tank 2
It obtains when carrying out first layer Cotton seeds to pellet, directly can be directly introduced to add by internal layer coating sustained release agent and texturizers
Carry out heating melting in thermal agitation tank 2 and internal layer coating liquid be made, then by charging pump 22 by internal layer coating liquid from heating stirring
It extracts out in tank 2 and is sprayed onto in coating pan via atomizing lance 23, and then head layer coating micro-pill is made in uniform be wrapped on pellet,
Similarly when preparing double-layer coatings pellet, can outer layer coating sustained release agent and texturizers be directly put into togerther heating and stirred
It mixes and carries out heating melting in tank outer layer coating liquid is made, being made by the setting of heating and stirring tank can be direct by seed-coating machine
Uniformly mixed inside and outside layer coating solution is made, then again will into without inside and outside layer coating solution is first made by other equipment
Inside and outside layer coating solution, which is put into seed-coating machine, is coated processing, not only improves the coating effect twice to pellet, also saves
Operating time, and then the production efficiency improved.
Stirring rod 100 is equipped in the coating pan 1, one end of the stirring rod 100 is solid with 11 output shaft of the first driving motor
Fixed connection, the other end of stirring rod 100 coordinate with 1 top of the coating pan, can be slided with respect to the top of coating pan；Preferably,
100 end of stirring rod is bent to form the hook portion of a L-type, and the coating pan boiler port is equipped with the sliding slot of annular, which is placed in
In the sliding slot, it can be moved along sliding slot；Further, stirring rod 100 is arranged for arc shape, the radian phase of radian and coating pan
Together, so that the wherein side side of stirring rod can be fitted on the inner wall of coating pan；And then it is sprayed in spray gun 23 same
When, the rotation of the first driving motor 11 drives stirring rod 100 to rotate, and the rotation of stirring rod can both allow coating more uniform, may be used also
To prevent material to be sticked on 1 inner wall of coating pan, it will effectively be sticked to material on coating pan inner wall and clear up；Preferably, institute
It states the cross section of stirring rod 100 for triangular structure to be arranged, preferably the material on coating pan inner wall can be struck off.
Further, the heating and stirring tank 2 includes tank body 3, the stir chamber 31 in the tank body, shaft 32, leaf
Wheel 33, the endless metal wiper 4 being in contact with 31 side wall of the stir chamber in the stir chamber 31 and the endless metal
4 matched driving part of wiper and for drive the shaft 32 rotate the second driving motor 34, the driving part can
The endless metal wiper 4 is driven to move up and down when the shaft 32 rotates；Specifically, the driving part includes being set to institute
State the placing chamber 35 in tank body 3, the driving gear 36 that coordinates with 32 rotation stop of the shaft in the placing chamber, with the master
The lead screw 38 for driven gear 37 and 37 rotation stop of the driven gear cooperation that moving gear 36 is meshed is sheathed on the lead screw
Sliding block 39 and the magnet piece 5 on the sliding block；Specifically, the tank body 3 and stir chamber 31 are all cylinder, the tank
The top of body 3 is provided with feed inlet, and tank body 3 is provided with the discharging being connected with the conveying pipeline 21 on the side wall of bottom
Mouthful, second driving motor 34 is the AC servo motor being arranged at the top of tank body 1, and when work can carry out positive and negative
Turn, structure and principle are the prior art, and this will not be repeated here, and the number of the driven gear 37 and lead screw 38 is all 4, described
4 being provided at circumferentially spaced along driving gear 36 of driven gear 37, described 4 lead screws 38 are vertically arranged and respectively along tank body
Uniformly top and driven gear 37 are connected for 1 circumferentially-spaced, and further, 35 inner wall of the placing chamber is equipped with for limiting
The bearing block of position lead screw 38, lead screw 38 are interference fitted with the bearing on bearing axis, and then can prevent lead screw from vertical direction occurs
Offset, when 34 drive shaft 32 of the second driving motor rotates clockwise, since driving gear 36 and 32 rotation stop of shaft coordinate,
And then driving gear 36 can be rotated clockwise with shaft 32 together edge, and then driven gear 37 and lead screw 38 is driven to turn together
It is dynamic, enable to the sliding block 39 for being provided with magnet piece 5 to move down when lead screw 38 rotates, and then in magnet piece 5 to annular gold
Under the sucking action for belonging to wiper 4, endless metal wiper 4 is enabled to move down and occur with 31 side wall of stir chamber relatively sliding
Dynamic, when the second driving motor rotates in the counterclockwise direction, sliding block moves up under the action of lead screw at this time, same annular
Metalwork can move up in the case where magnet piece attracts force effect and opposite sliding occurs with stir chamber side wall, pass through endless metal
Moving up and down for part all can not only will be extracted this under the material scraper being attached on stir chamber side wall conducive to material
In tank body, additionally it is possible to the material of stir chamber lateral wall circumference has been stirred, so that the material mixing in stir chamber is more uniform,
And then it can not all be extracted and inside and outside layer coating solution by inside and outside layer coating solution made from the heating and stirring tank
Mixture homogeneity higher, to improve the quality of the coating type veterinary drug pill.
Further, 4 top of the annular metalwork is to be obliquely installed, and then material is prevented to remain in annular metalwork
Upper surface.
Further, 4 side of the annular metalwork is equipped with two cyclic annular raised lines 41, specifically, described two cyclic annular raised lines 41
In it is setting up and down on the outside of annular metalwork on, the cross section of the raised line is a laterally disposed isosceles trapezoid, passes through isosceles
Trapezoidal setting reduces annular metalwork and stirs the contact area between cavity wall, and then conducive to annular metalwork in magnet
The attraction force effect of block issues raw up and down action, and the upper and lower surface additionally, due to the raised line is all to be obliquely installed, and not only material is not
Easily remain on raised line upper surface, and reduce the material resistance that raised line is subject to when moving up and down, is further convenient for annular gold
Belong to the up and down action of part.
Further, the raised line 41 is circumferentially spaced is evenly arranged with multiple vertical through-holes 411, and the vertical through-hole passes through
The upper and lower surface for wearing raised line can will remain in the material between two raised lines by the setting of through-hole and be discharged.
Further, the annular metalwork 4 is equipped with multiple arcs and stirs part 42, specifically, the agitation part 42
Cross section is laterally disposed isosceles trapezoid, and the agitation part 42 is 6, and described 6 agitation parts are arranged in annular metalwork
Inside and be uniformly arranged along the circumferentially-spaced of annular metalwork, by stir part setting annular metalwork is moved down upper
When dynamic, the material agitation of stir chamber lateral wall circumference can be greatly will be close to, so that the material in stir chamber
What is mixed is more uniform, is tilted from top to bottom additionally, due to the upper surface of agitation part, and lower surface tilts from bottom to top, and then stirs
The material resistance that part is subject to when moving up and down is smaller, and material is not easy to remain on agitation part.
Further, the tank body 3 is equipped with heater 6 at the position below stir chamber 31, specifically, the heater
6 be heating wire, can be heated to stir chamber by heater, and then carries out heating melting by launching to the material in stir chamber
Processing.
Further, the hot air apparatus includes hot blast pipe 7, the infrared heater being connect with the hot blast pipe 8 and institute
State the blast pipe 9 that infrared heater is connected and the air blower 10 set on described blast pipe one end, the outlet air of the hot blast pipe 7
Mouth is extend into coating pan 1, and the wind that air blower 10 sucks is ejected into after infrared heater heats from the air outlet of hot blast pipe
In coating pan, and then except the moisture of decaptitating layer coating micro-pill and double-layer coatings pellet, to which final coating type veterinary drug ball be made
Agent.
Embodiment 2：
A kind of coating type veterinary drug pill, is made of the supplementary material of following masses score：
Specific preparation method is as follows：
(1) Tilmicosin 20kg, cornstarch 35kg, white bole are weighed respectively by the mass fraction percentage
15.7kg, rilanit special 10kg, PEG-6000 3kg, PEG-4000 1kg, oil with hydrogenated soybean 6kg, agar powder 4kg, saccharin
Each 0.4kg of sodium, Aspartame, microcrystalline cellulose 3kg, PVPk90 1.5kg, it is spare；
(2) Tilmicosin, cornstarch, white bole, saccharin sodium, Aspartame are uniformly mixed, and 2- is first used in extruder
The wetting of 3kg water squeezes granulation, then pellet is made by the way that the further ball blast of shot-blasting machine is moulding, and the pellet water content control is 5%
Within；
(3) it is the first additive that PEG-6000 2kg are taken after, then by the first additive and 10kg rilanit specials one
It plays heating to melt and microcrystalline cellulose 2kg is added, stirs evenly and be configured to internal layer coating liquid, temperature is maintained at 80~85 DEG C；
(4) pellet obtained in step (2) is put into seed-coating machine, internal layer coating buffer is added in seed-coating machine at coating
30 minutes blowings are managed to get head layer coating micro-pill；
(5) it takes agar powder 4kg that distilled water is added, is heated to agar powder and is completely dissolved, obtain agar solution；Take PEG-6000
It is uniformly mixed to get the second additive with each 1kg of PEG-4000, then adds the second additive and oil with hydrogenated soybean 10kg together
Simultaneously microcrystalline cellulose 1kg is added in heat fusing, and agar solution is configured to outer layer coating liquid, and temperature is maintained at 60~65 DEG C；
(6) the head layer coating micro-pill obtained in step (4) is put into seed-coating machine, seed-coating machine is added in outer layer coating liquid
30 minutes blowings of middle Cotton seeds take -80 mesh of 24 mesh to sieve, by double-layer coatings pellet to get double-layer coatings pellet, screened processing
Size controlling at 200~800 μm to get finished product.
Embodiment 3：
A kind of coating type veterinary drug pill, is made of the supplementary material of following masses score：
Specific preparation method is as follows：
(1) Tilmicosin 20kg, cornstarch 35kg, lactose 15.7kg are weighed respectively by the mass fraction percentage,
Rilanit special 10kg, PEG-6000 and PEG-4000 each 2kg, oil with hydrogenated soybean 6kg, agar powder 4kg, saccharin sodium 0.6kg, Ah
This Ba Tian 0.2kg, microcrystalline cellulose 3kg, PVP 1.5kg are spare；
(2) Tilmicosin, cornstarch, lactose, saccharin sodium, Aspartame are uniformly mixed, and 2-3kg is first used in extruder
Water wetting squeezes granulation, then is made pellet by the way that the further ball blast of shot-blasting machine is moulding, the pellet water content control 5% with
It is interior；
(3) it is the first additive to take PEG-4000 2kg, then adds the first additive and 10kg rilanit specials together
Heat fusing and microcrystalline cellulose 2kg is added, PVPk30 1kg is stirred evenly and is configured to internal layer coating liquid, temperature is maintained at 80~85
℃；
(4) pellet obtained in step (2) is put into seed-coating machine, internal layer coating buffer is added in seed-coating machine at coating
30 minutes blowings are managed to get head layer coating micro-pill；
(5) it takes agar powder 4kg that distilled water is added, is heated to agar powder and is completely dissolved, obtain agar solution；Take PEG-6000
2kg is the second additive, then heats the second additive and oil with hydrogenated soybean 10kg together and melts and microcrystalline cellulose is added
1kg, PVPk30 0.5kg, agar solution are configured to outer layer coating liquid, and temperature is maintained at 60~65 DEG C；
(6) the head layer coating micro-pill obtained in step (4) is put into seed-coating machine, seed-coating machine is added in outer layer coating liquid
30 minutes blowings of middle Cotton seeds take -80 mesh of 24 mesh to sieve, by double-layer coatings pellet to get double-layer coatings pellet, screened processing
Size controlling at 200~800 μm to get finished product.
Embodiment 4：
A kind of coating type veterinary drug pill, is made of the supplementary material of following masses score：
Specific preparation method is as follows：
(1) Tilmicosin 20kg, cornstarch 35kg, maltodextrin are weighed respectively by the mass fraction percentage
12kg, lactose 6.1kg, rilanit special 9kg, PEG-6000 and PEG-4000 each 1.8kg, oil with hydrogenated soybean 5.5kg, agar powder
3.5kg, saccharin sodium 0.6kg, Aspartame 0.2kg, microcrystalline cellulose 2kg, PVPk30 2.5kg are spare；
(2) Tilmicosin, cornstarch, maltodextrin, lactose, saccharin sodium, Aspartame are uniformly mixed, first in extruder
It is interior to squeeze granulation with the wetting of 2-3kg water, then pellet, the pellet water content control is made by the way that the further ball blast of shot-blasting machine is moulding
Within 5%；
(3) PEG-4000 1.8kg are taken to obtain the first additive, then together by the first additive and 9kg rilanit specials
Heating melts and microcrystalline cellulose 1kg is added, PVPk30 1kg is stirred evenly and is configured to internal layer coating liquid, and temperature is maintained at 80~
85℃；
(4) pellet obtained in step (2) is put into seed-coating machine, internal layer coating buffer is added in seed-coating machine at coating
30 minutes blowings are managed to get head layer coating micro-pill；
(5) it takes agar powder 3.5kg that distilled water is added, is heated to agar powder and is completely dissolved, obtain agar solution；Take PEG-
6000 1.8kg obtain the second additive, then heat the second additive and oil with hydrogenated soybean 9kg together and melt and be added micro-
Crystalline cellulose 1kg, PVPk301.5kg, agar solution are configured to outer layer coating liquid, and temperature is maintained at 60~65 DEG C；
(6) the head layer coating micro-pill obtained in step (4) is put into seed-coating machine, seed-coating machine is added in outer layer coating liquid
30 minutes blowings of middle Cotton seeds take -80 mesh of 24 mesh to sieve, by double-layer coatings pellet to get double-layer coatings pellet, screened processing
Size controlling at 200~800 μm to get finished product.
Embodiment 5：
A kind of coating type veterinary drug pill, is made of the supplementary material of following masses score：
Specific preparation method is as follows：
(1) Tilmicosin 25kg, cornstarch 30kg, maltodextrin are weighed respectively by the mass fraction percentage
14.2kg, rilanit special 11kg, PEG-6000 and PEG-4000 each 1.5kg, oil with hydrogenated soybean 8kg, agar powder 3kg, saccharin
Sodium 0.5kg, Aspartame 0.3kg, microcrystalline cellulose 3kg, PVPk30 2kg are spare；
(2) Tilmicosin, cornstarch, maltodextrin, saccharin sodium, neotame are uniformly mixed, and 2-3kg is first used in extruder
Water wetting squeezes granulation, then is made pellet by the way that the further ball blast of shot-blasting machine is moulding, the pellet water content control 5% with
It is interior；
(3) PEG-4000 1.5kg are taken to obtain the first additive, then by the first additive and 11kg rilanit specials one
Rise heating melt and microcrystalline cellulose 1kg is added, PVPk30 1kg is stirred evenly and is configured to internal layer coating liquid, temperature is maintained at 80
~85 DEG C；
(4) pellet obtained in step (2) is put into seed-coating machine, internal layer coating buffer is added in seed-coating machine at coating
30 minutes blowings are managed to get head layer coating micro-pill；
(5) it takes agar powder 3kg that distilled water is added, is heated to agar powder and is completely dissolved, obtain agar solution；Take PEG-6000
1.5kg obtains the second additive, then heats the second additive and oil with hydrogenated soybean 11kg together and melts and be added crystallite fibre
Dimension element 2kg, PVPk30 1kg, agar solution are configured to outer layer coating liquid, and temperature is maintained at 60~65 DEG C；
(6) the head layer coating micro-pill obtained in step (4) is put into seed-coating machine, seed-coating machine is added in outer layer coating liquid
30 minutes blowings of middle Cotton seeds take -80 mesh of 24 mesh to sieve, by double-layer coatings pellet to get double-layer coatings pellet, screened processing
Size controlling at 200~800 μm to get finished product.
Embodiment 6：
A kind of coating type veterinary drug pill, is made of the supplementary material of following masses score：
Specific preparation method is as follows：
(1) Tilmicosin 30kg, cornstarch 30kg, maltodextrin are weighed respectively by the mass fraction percentage
10.2kg, rilanit special 11kg, PEG-6000 and PEG-4000 each 1.5kg, oil with hydrogenated soybean 8kg, agar powder 3kg, A Si
Ba Tian 0.2kg, neotame 0.6kg, microcrystalline cellulose 2kg, PVPk30 2kg are spare；
(2) Tilmicosin, cornstarch, maltodextrin, Aspartame, neotame are uniformly mixed, and 2- is first used in extruder
The wetting of 3kg water squeezes granulation, then pellet is made by the way that the further ball blast of shot-blasting machine is moulding, and the pellet water content control is 5%
Within；
(3) PEG-4000 1.5kg are taken to obtain the first additive, then by the first additive and 11kg rilanit specials one
It plays heating and melts and microcrystalline cellulose 1kg, PVPk30 1kg is added stirs evenly and be configured to internal layer coating liquid, temperature is maintained at 80
~85 DEG C；
(4) pellet obtained in step (2) is put into seed-coating machine, internal layer coating buffer is added in seed-coating machine at coating
30 minutes blowings are managed to get head layer coating micro-pill；
(5) it takes agar powder 3kg that distilled water is added, is heated to agar powder and is completely dissolved, obtain agar solution；Take PEG-6000
1.5kg obtains the second additive, and the second additive and oil with hydrogenated soybean 11kg are then heated melting together, and crystallite fibre is added
Element 1kg, PVPk301kg are tieed up, agar solution is configured to outer layer coating liquid, and temperature is maintained at 60~65 DEG C；
(6) the head layer coating micro-pill obtained in step (4) is put into seed-coating machine, seed-coating machine is added in outer layer coating liquid
30 minutes blowings of middle Cotton seeds take -80 mesh of 24 mesh to sieve, by double-layer coatings pellet to get double-layer coatings pellet, screened processing
Size controlling at 200~800 μm to get finished product.
Above example be the present invention technology implementation process in a small number of illustrations for being lifted, will not be to the present invention's
Application range forms limitation.As long as that is done on the basis of the present invention is not essential improvement can be assumed that it is in the present invention
Within protection domain.
Contrast experiment 1：Cross inspection experiment.
Common micro-capsule Tilmicosin, normal packet are compared by Tilmicosin and Tilmicosin content detection diversity factor of the present invention,
Whether judge being capable of effective detection level in strict accordance with National Standard Method (2015 editions veterinary drug allusion quotations).
Experimental group：The embodiment of the present invention 1, embodiment 3,5 taste masking of embodiment are sustained Tilmicosin.
Control group：Common micro-capsule Tilmicosin, normal packet are by Tilmicosin.
Experimental method：
National Standard Method detection is per a sample size, based on the percentage of labelled amount；
It ground per portion sample, use National Standard Method detection level after hot melt again, based on the percentage of labelled amount；
It is attached：High performance liquid chromatography in national standard.Take this product appropriate (being approximately equivalent to Tilmicosin 0.25g), it is accurately weighed, it sets
In 50ml measuring bottles, add extracting solution 25ml, add acetonitrile 200ml, add water to 1000ml] 40ml, it is ultrasonically treated 10 minutes, lets cool, use
Said extracted liquid is diluted to scale, and filtration, precision measures subsequent filtrate 5ml, sets in 50ml measuring bottles, quarter is diluted to phosphoric acid solution
Degree, shakes up.Precision measures 10 μ l, injects liquid chromatograph, records chromatogram.Tilmicosin reference substance about 25mg separately is taken, it is accurate
It is weighed, it sets in 50ml measuring bottles, adds acetonitrile 10ml supersound process to make dissolving, be diluted to scale with above-mentioned phosphoric acid solution, shake up, same to method
It measures.By external standard method with cis and trans isomer peak area and calculate to get.
Wherein, the preparation method of extracting solution is：Phosphoric acid dibutyl amine solution, dibutyl amine 16.8ml are taken respectively, and phosphorate acid solution
(1 → 10) 70ml, it is stirring while adding, after letting cool, with phosphorus acid for adjusting pH value to 2.5 ± 0.1, add water to 100ml；The phosphoric acid is molten
The preparation method of liquid is：Take phosphoric acid 5.71g, add water 900ml 12.5mol/L sodium hydroxide solutions adjust pH value to 2.5 ±
0.1, add water to 1000ml.
3, above-mentioned 1,2 two kind of detection mode content balance, and judge whether product is crossed and examine.
Experimental result：
1 content detection Comparative result of table
| Sample | National Standard Method/% | Grinding, hot melt/% |
| Common micro-capsule Tilmicosin | 72.36 | 96.83 |
| Certain producer's Tilmicosin | 89.77 | 98.42 |
| Embodiment 1 | 97.15 | 97.96 |
| Embodiment 3 | 98.03 | 98.07 |
| Embodiment 5 | 97.98 | 98.12 |
By experimental result it is found that coating type veterinary drug pill of the present invention measures content results by National Standard Method and grinding, hot melt
It is sufficiently close to, illustrates to be fully able to really detect content by National Standard Method detection, meet national standard.And common micro-capsule is examined for rice
Star and certain producer's Tilmicosin two methods detection level difference are larger, and especially common micro-capsule differs 24.47% for meter Han Liang, nothing
The accurate detection level of method, although may taste masking, slow release effect it is preferable, product cannot cross inspection, not meet national requirements.
Contrast experiment 2：Taste masking is tested.
Experimental group：The coating type veterinary drug pill that embodiment 1, embodiment 3, embodiment 5 produce
Control group：Normal packet is by product 1, and normal packet is by product 2
Experimental method：
Each sample weighs 1g, is soaked in respectively in 50ml edible white vinegars, shakes manually, and 5min stops, artificial to taste
Light-coloured vinegar judges bitterness, is calculated as substantially not bitter, acceptable, more bitter, very bitter four degree, and each sample gargles three before tasting
Time.
Experimental result：
2 taste masking effect of table compares
The results show that product taste masking effect of the present invention is ideal.
Contrast test 3：Feeding experiment.
Judge feeding Preference of the weanling pig to different brands tilmicosin micro-capsule preparation.
Control group：Basal diet, I group of Tilmicosin (Tilmicosin of the present invention), II group of Tilmicosin (are sold certain coating and are replaced in city
Meter Kao Xing)
Test pig：It does two groups of repetitions, chooses the piglet of 2 column child care mid-term of Zhejiang pasture (per 25, column)
Test procedure：
1. setting group 1 is blank control group, group 2 is II group I group of Tilmicosin, group of 3 Tilmicosin；By replacing for different brands
Meter Kao Xing preparations are added to according to the ratio of 2kg/t in child care powder, are stirred and evenly mixed by way of premix.
2. placing three hoppers respectively in two columns, the position of hopper is replaced per half a day, to avoid foraging behaviour inertia institute
Caused deviation, initial position are as shown in Figure 1.
3. experiment two days by a definite date, after by hopper residual feed collection weigh, calculate feed intake.
Test result：
2. piglet feed intake
3 piglet feed intake record sheet of table
It analyzes according to the observation, the inertia feeding of piglet can influence the feeding head number of each group to a certain extent, close to bubbler
Hopper piglet feeding head number it is more；But the not no inevitable relationship of head number and the feed intake of searching for food.With regard in the first column from the point of view of feed intake
Three groups of feed intakes are more balanced, and two groups of data, which all demonstrate, to be premixed the feed of tilmicosin micro-capsule preparation of the present invention and will not cause son substantially
Pig mouthfeel discomfort is to reduce feed intake, feed intake no significant difference compared to the control group.And certain Tilmicosin and this hair are sold by city
It is bright poor compared to palatability.
Contrast experiment 4：In Vitro Dissolution is tested.
The coating type veterinary drug pill that embodiment 1, embodiment 3, embodiment 5 produce
Dissolution experiment is done in digestion instrument by product 2 by product 1, normal packet with normal packet, compares release rate.
Experimental method：
1, stomach discharges.Precision weighs a certain number of Tilmicosins (about 2g) and is placed in a Nylon Bag, by Nylon Bag
It ties up on agitating paddle, is added in 500ml gastric juice (2g pepsins are added in per 1L 0.075M hydrochloric acid solutions) to digestion instrument, adjusts
PH to 2.8 is saved, at 39 DEG C, 200 turns/min, under the conditions of, simulate the gastric juice reaction, while adjusting a pH to 2.8 every 20 minutes.
The sample detection in 05h, 2h respectively in the process.
2, enteron aisle discharges.Nylon Bag by stomach release is tied up and is transferred on agitating paddle in 500ml intestinal juice digestion instruments, is adjusted
PH is saved to 7.4, while a pH to 7.4 was adjusted every 20 minutes.Under the conditions of 39 DEG C, 200 turns/min, simulation enteron aisle release.
The sample detection in 2,4,6,8,10,12h respectively in the process；Wherein, the intestinal juice be phosphate buffer (PH 7.4,
1L is made with distilled water in 80ml0.2M dibastic sodium phosphates and 420ml 0.2M disodium hydrogen phosphates), interior phosphate buffer includes pancreatin (1g
Pancreatin/L).
Experimental result：
5 each sample In Vitro Dissolution of table tests gastrointestinal tract release rate comparison result
By In Vitro Dissolution experimental result and as shown in Figure 2 it is found that product gastric juice 2h release rates of the embodiment of the present invention are 20%
Left and right, release rate is relatively low, the uniform slow release in intestinal juice, and release rate reaches 95%-97% after 12h, and slow release effect is apparent, and three
A embodiment sample result is substantially close.Normal packet has reached 64.93% by 1 gastric juice 2h release rates of product, and stomach discharged
Soon, for release rate up to 93.06%, slow release effect is poor after intestinal juice 2h.Normal packet had good sustained release effect in gastric juice by product 2, but into
Enter similar by product 1 to normal packet after intestinal juice, release is too fast in the short time, is unfavorable for being absorbed and utilized for drug.
Contrast test 5：Pharmacokinetics is tested.
Test site：Zhejiang pig farm.
Test method：20mg/kg dosage Tilmicosin original powder and tilmicosin micro-capsule preparation (1 product of the embodiment of the present invention and
Certain coating Tilmicosin product is in terms of 20% Tilmicosin, 100mg preparations) administration is gavaged, then gavage 20mL water.(such as 8kg is young
Pig is just administered with 160mg original powders；1 product of the embodiment of the present invention and certain coating Tilmicosin product are in terms of 20% Tilmicosin.)
Original powder group and preparation group select sodium selenite similar in 3 sizes, are taken a blood sample by piglet vena cava anterior.Test fasted for one day prior
12h.The experiment same day, every piglet gavage administration with 20mg/kg dosage.15min, 30min after perfusion, 45min, 1h, 2h, 3h,
4h, 6h, 8h, 12h, for 24 hours, 36h, 48h acquire blood, acquire whole blood 2mL every time.The new blood being collected is placed in heparin sodium
In centrifuge tube, 5min is centrifuged with 8000r/min, separated plasma is simultaneously stored in -80 DEG C.Blood concentration is measured, every group is averaged.
Test result：As shown in Figure 3.
From the figure 3, it may be seen that area is aobvious under the peak drug levels and drug-time curve of coating type veterinary drug pill prepared by the present invention
It writes and is higher than Tilmicosin original powder.It is compared with certain coating product, area is significantly greater under product drug-time curve of the present invention, but medicine peak
Concentration is slightly lower, and peak time is slightly slow, this, which further illustrates the present invention product, has good slow release effect, avoids Tilmicosin
The cardiac toxic and allergic reaction that high dose generates when applying.
Obviously, described embodiment is only a part of the embodiment of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment should all belong to the scope of protection of the invention.
Claims (8)
1. a kind of coating type veterinary drug pill, it is characterised in that：Including following mass fraction than component：Tilmicosin 20-30%,
Carrier material 39.2-56.5%, internal layer coating sustained release agent 10-12.5%, outer layer coating sustained release agent 10-12.5%, corrigent 0.5-
0.8%, texturizers 3-5%；The outer layer coating sustained release agent is the mixture of oil with hydrogenated soybean, the second additive and agar.
2. a kind of coating type veterinary drug pill according to claim 1, it is characterised in that：The oil with hydrogenated soybean, second add
It is 5 to add the mass ratio of object and agar:1:2-3:1:2.
3. a kind of coating type veterinary drug pill according to claim 1, it is characterised in that：The internal layer coating sustained release agent includes
The mass ratio of rilanit special and the first additive, the rilanit special and the first additive is 8:1-5:1；Described first adds
Object is added to be combined for one or both of PEG6000 and PEG4000.
4. a kind of coating type veterinary drug pill according to claim 1, it is characterised in that：Second additive is
One or both of PEG6000 and PEG4000 are combined.
5. a kind of coating type veterinary drug pill according to claim 1, it is characterised in that：The corrigent be saccharin sodium, Ah
One or more of this Ba Tian and neotame are combined.
6. a kind of coating type veterinary drug pill according to claim 1, it is characterised in that：The texturizers are that crystallite is fine
One or more of dimension element, PVPk30 and PVPk90 combinations.
7. a kind of preparation method of coating type veterinary drug pill as described in any one of claim 1-6, it is characterised in that：Including
Following steps：
Tilmicosin, carrier material, ectonexine coating sustained release agent, corrigent, group are weighed respectively by the mass fraction percentage
It is spare to knit modifier；
Tilmicosin, carrier material and corrigent are uniformly mixed, is first soaked with water in extruder and squeezes granulation, then pass through throwing
The further ball blast of ball machine is moulding to be made pellet, and the pellet water content control is within 5%；
C, internal layer coating sustained release agent being heated and is melted, texturizers are added and are configured to internal layer coating liquid, temperature is maintained at 80~
85℃；
D, the pellet obtained in step b is put into seed-coating machine, Cotton seeds 30 in seed-coating machine, which are added, in internal layer coating liquid divides
Clock blowing is to get head layer coating micro-pill；
E, outer layer coating sustained release agent being heated and is melted, texturizers are added and are configured to outer layer coating liquid, temperature is maintained at 60~
65℃；
F, the head layer coating micro-pill obtained in step d is put into seed-coating machine, outer layer coating liquid is added in seed-coating machine and is coated
30 minutes blowings are handled to get double-layer coatings pellet, screened processing takes -80 mesh of 24 mesh to sieve, by the grain size of double-layer coatings pellet
Control is at 200~800 μm to get finished product.
8. a kind of preparation method of coating type veterinary drug pill according to claim 7, it is characterised in that：The tissue improves
Additive amount of the agent in internal layer coated slow release agent is the 40%-70% of texturizers total amount.
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| CN201810656720.1A CN108653230A (en) | 2018-06-24 | 2018-06-24 | Coating type veterinary drug pill and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810656720.1A CN108653230A (en) | 2018-06-24 | 2018-06-24 | Coating type veterinary drug pill and preparation method thereof |
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| Publication Number | Publication Date |
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| CN108653230A true CN108653230A (en) | 2018-10-16 |
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ID=63773131
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109464413A (en) * | 2018-12-04 | 2019-03-15 | 中牧实业股份有限公司黄冈动物药品厂 | A kind of Tilmicosin pellet and preparation method thereof |
| CN110314094A (en) * | 2019-07-09 | 2019-10-11 | 安徽海康药业有限责任公司 | A kind of Ni Lapani electuary and preparation method thereof efficiently utilized |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586774A (en) * | 2015-01-26 | 2015-05-06 | 成都乾坤动物药业有限公司 | Process for preparing tilmicosin pellets |
| CN104983718A (en) * | 2015-07-17 | 2015-10-21 | 江西博莱大药厂有限公司 | Tilmicosin slow release pellet, and preparation method and application thereof |
| CN106176671A (en) * | 2016-08-30 | 2016-12-07 | 天津市中升挑战生物科技有限公司 | A kind of tasteless tilmicosin granule and preparation method thereof |
-
2018
- 2018-06-24 CN CN201810656720.1A patent/CN108653230A/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586774A (en) * | 2015-01-26 | 2015-05-06 | 成都乾坤动物药业有限公司 | Process for preparing tilmicosin pellets |
| CN104983718A (en) * | 2015-07-17 | 2015-10-21 | 江西博莱大药厂有限公司 | Tilmicosin slow release pellet, and preparation method and application thereof |
| CN106176671A (en) * | 2016-08-30 | 2016-12-07 | 天津市中升挑战生物科技有限公司 | A kind of tasteless tilmicosin granule and preparation method thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109464413A (en) * | 2018-12-04 | 2019-03-15 | 中牧实业股份有限公司黄冈动物药品厂 | A kind of Tilmicosin pellet and preparation method thereof |
| CN110314094A (en) * | 2019-07-09 | 2019-10-11 | 安徽海康药业有限责任公司 | A kind of Ni Lapani electuary and preparation method thereof efficiently utilized |
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