CN104784123B - A kind of centrifugal process prepares Tilmicosin enteric-coated micro-pill technique - Google Patents
A kind of centrifugal process prepares Tilmicosin enteric-coated micro-pill technique Download PDFInfo
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- JTSDBFGMPLKDCD-XVFHVFLVSA-N tilmicosin Chemical compound O([C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CCN1C[C@H](C)C[C@H](C)C1)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@@H]1O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]1O JTSDBFGMPLKDCD-XVFHVFLVSA-N 0.000 title claims abstract description 55
- 229960000223 tilmicosin Drugs 0.000 title claims abstract description 53
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- 239000006187 pill Substances 0.000 title claims abstract description 35
- 230000008569 process Effects 0.000 title claims abstract description 17
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- 238000000576 coating method Methods 0.000 claims abstract description 17
- 239000008188 pellet Substances 0.000 claims abstract description 14
- 239000000853 adhesive Substances 0.000 claims abstract description 12
- 230000001070 adhesive effect Effects 0.000 claims abstract description 12
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- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 11
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- 239000002245 particle Substances 0.000 claims description 44
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- 241001676635 Lepidorhombus whiffiagonis Species 0.000 claims description 6
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- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
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- 239000007864 aqueous solution Substances 0.000 claims description 5
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- 229930091371 Fructose Natural products 0.000 claims description 4
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 4
- 239000004594 Masterbatch (MB) Substances 0.000 claims description 4
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- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 239000004744 fabric Substances 0.000 claims description 2
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- 230000000968 intestinal effect Effects 0.000 abstract description 15
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- 238000002360 preparation method Methods 0.000 abstract description 7
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- 239000002994 raw material Substances 0.000 abstract description 6
- 238000010521 absorption reaction Methods 0.000 abstract description 2
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- 241001465754 Metazoa Species 0.000 description 6
- 241000209094 Oryza Species 0.000 description 6
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- 235000021050 feed intake Nutrition 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 235000009566 rice Nutrition 0.000 description 6
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- 238000010171 animal model Methods 0.000 description 4
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- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000000889 atomisation Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 244000144972 livestock Species 0.000 description 3
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- 241000283690 Bos taurus Species 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- 229930194936 Tylosin Natural products 0.000 description 2
- 239000004182 Tylosin Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
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- 210000004080 milk Anatomy 0.000 description 2
- 239000003182 parenteral nutrition solution Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000007493 shaping process Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- WBPYTXDJUQJLPQ-VMXQISHHSA-N tylosin Chemical compound O([C@@H]1[C@@H](C)O[C@H]([C@@H]([C@H]1N(C)C)O)O[C@@H]1[C@@H](C)[C@H](O)CC(=O)O[C@@H]([C@H](/C=C(\C)/C=C/C(=O)[C@H](C)C[C@@H]1CC=O)CO[C@H]1[C@@H]([C@H](OC)[C@H](O)[C@@H](C)O1)OC)CC)[C@H]1C[C@@](C)(O)[C@@H](O)[C@H](C)O1 WBPYTXDJUQJLPQ-VMXQISHHSA-N 0.000 description 2
- 229960004059 tylosin Drugs 0.000 description 2
- 235000019375 tylosin Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 241000606748 Actinobacillus pleuropneumoniae Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
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- 241001494479 Pecora Species 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 201000005010 Streptococcus pneumonia Diseases 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
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- 230000005484 gravity Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 229940041033 macrolides Drugs 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
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- BUKHSQBUKZIMLB-UHFFFAOYSA-L potassium;sodium;dichloride Chemical compound [Na+].[Cl-].[Cl-].[K+] BUKHSQBUKZIMLB-UHFFFAOYSA-L 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
Tilmicosin enteric-coated micro-pill technique is prepared the invention discloses a kind of centrifugal process, it is made up of following materials in percentage by mass after pill, coating of pellets is centrifuged：Tilmicosin 21~26%, adhesive 10~20%, microcrystalline cellulose 23~30% and coating material 10~20%.The Tilmicosin enteric-coated micro-pill envelop rate that the present invention is provided is high, the bitter taste of Tilmicosin can well be covered, and it is all in dissolution in intestinal environment, can be used as enteric slow release reagent, the adverse reaction that absorption band comes in stomach is solved, its preparation process is simple, raw material is cheap and easy to get, it is adapted to industrialization large-scale production, therefore its application prospect is very wide.
Description
Technical field
Tilmicosin enteric-coated micro-pill technique is prepared the present invention relates to centrifugal process, belongs to veterinary drug preparing technical field.
Background technology
Tilmicosin be tylosin through the derivative after sour water solution, be semi-synthetic macrolides animal specific antibiosis
Element, its molecular formula is C46H80N2O13, molecular weight 869.15, its Australia, Brazil, France, Malaysia, Italy,
The countries such as Spain, the U.S. are approved for clinic.Tilmicosin has the antibacterial activity similar to Macrocyclolactone lactone kind medicine, right
Gram-positive bacteria is effective with some Gram-negative bacterias and mycoplasma.Especially to Actinobacillus pleuropneumoniae, pasteurella,
The activity of staphylococcus aureus, streptococcus pyogenes, streptococcus pneumonia, corynebacterium pyogenes and livestock and poultry mycoplasma compares tylosin
It is stronger.Clinically it is mainly used in the animals such as treatment ox, goat, sheep, milk cow, pig, chicken by sensitive microbial infectious diseases,
Particularly livestock and poultry respiratory tract infection and sensitive microbial mastitis for milk cows.
But, due to Tilmicosin raw material, palatability is poor in itself, there is certain stimulation to stomach, and animal mixed feeding goes out often
The phenomenon that existing food refusal is even vomitted, seriously constrains its application in livestock and poultry prevention and treatment.At present, in the market is common
Tilmicosin micro-capsule preparation have the products such as oral liquid, parenteral solution, pre-mixing agent.It is poor in the absence of palatability because parenteral solution is not by oral
Problem, but because clinical practice is comparatively laborious, toxic and side effect is larger, can not cut Tilmicosin in disease large-scale outbreak
Real performance maximum effect；Other preparations such as oral liquid, pre-mixing agent etc. belong to oral conventional formulation, all fail to solve to be examined for rice
The problem of star palatability difference.
Existing Tilmicosin pill method uses extrusion spheronization technique, not only cumbersome, high cost, and system mostly
Standby particle is presented the slightly sharp similar rice shape in two, and proper sphere degree can not show a candle to that the particle that pill making craft is made, Jin Erzao is centrifuged
Poor into coating efficiency, the coating became uneven of particle surface is even, it is oral after be easily degraded and absorbed in stomach, stomach is formed to stimulate
(particle requirement being coated with is not dissolved in stomach, is dissolved in enteron aisle).Additionally, particle prepared by extrusion spheronization technique is due to receiving
To the extruding of higher-strength, it is difficult to be completely dissolved release in small enteral, causes most of bulk drug to exclude external, causes environment dirty
Dye, this is also a very serious problem.
The content of the invention
In view of the above-mentioned problems existing in the prior art, it is simple it is an object of the invention to provide a kind of preparation method, low cost,
Clinical practice is simple, and toxic and side effect is small, and effect is powerful, good palatability, it is easy to which animal intestinal tract is absorbed, and pollution is not resulted in environment
Tilmicosin enteric-coated micro-pill preparation technology.
For achieving the above object, the technical solution adopted by the present invention is as follows：
A kind of centrifugal process prepares Tilmicosin enteric-coated micro-pill technique, is made up of the component of following weight percent content：Replace
Meter Kao Xing 21~26%, cornstarch 20~25%, adhesive 10~20%, microcrystalline cellulose 23~30% and coating material 10
~20%；What is prepared comprises the following steps that：
A) cornstarch, microcrystalline cellulose are weighed, is well mixed after adding Tilmicosin original powder, obtain powder；
B) 4~6Kg powders, rotary speed is added to be set as 90~110r/min, hydrojet in the rotating disk of centrifugation pellet processing machine
Pump hydrojet speed is set as 180~200ml/min, and it is 100~120m that air door intake is opened3/min；Be then turned on rotating disk with
Air feed, powder is lifted up in rotation process, and is constantly rolled under baffle effect, and the adhesive that Liquid spraying pump is sprayed into makes powder
Mutually bonded between fine-powder, the time continues 6~8 minutes, form the particle masterbatch of 60~80 mesh；
C) powder mixed toward continuous addition step a) gained in centrifugation pellet processing machine, is set as powder velocity original value
400g/min, 1000g/min is gradually increased to for powder speed；The initial speed of rotating disk is arranged on 100r/min, be gradually increased to
180r/min；And constantly penetrating binder solution carries out pill；The initial hydrojet speed of Liquid spraying pump is set as 200ml/ minutes, with
The increase of material addition is gradually increased to 500ml/min；Liquid spraying pump whiff pressure 0.2-0.25MPa；The opening degree of air door
Initial value is set as 100~120m3/ min, the later stage is enlarged to 220~240m3/min；When 30 mesh above particles account for 10% i.e.
Stop pill operation；
D) particle obtained by step c) is taken out into sieving again through drying, obtains the particle of 30~60 mesh；
E) particle obtained by step d) is sprayed into coating agent solutions to be coated, described Tilmicosin intestines is obtained final product after sieving
Molten micropill.
Cornstarch, microcrystalline cellulose sieving screen cloth are 80 mesh in step a) in the above method.
Adhesive described in the above method is selected from one or more the mixing in sucrose, HPMC, fructose
Thing.
It is formulated as 40% aqueous solution when above method is using sucrose, the concentration of aqueous solution of HPMC is 3%,
Fructose concentration of aqueous solution is 50%.
Coating Solution described in the above method is polyacrylic acid resin emulsion.
Polyacrylic acid resin emulsion concentration described in the above method is 30%.
Above method step c) stops for after powder and whitewashing, micropill still needs to continue to roll 4~6 minutes in centrifugation pellet processing machine
It is polished rear re-dry.
The particle that step c) is obtained is placed in fluid bed in above method step d) dries two with 50~55 DEG C of state
Hour.
Tilmicosin of the present invention is centrifuged pill parameter determination：
1st, rotary speed：
Material is mutually collided under the centrifugal action that turntable rotation is produced, and is coalesced by the viscous effect of adhesive
Pelletization.Rotary speed determines the size of centrifugal force, therefore also determines the formation of micropill to a certain extent.By repeatedly examination
Test, it was demonstrated that the rotating speed of rotating disk is arranged on 100~180r/min, be adapted to the operation of Tilmicosin micropill pill operation.Less than this turn
Speed, it may appear that particle is easily bonded, and outward appearance is not good, and then particle is broken higher than this rotating speed.
2nd, Liquid spraying pump hydrojet speed：
Liquid spraying pump hydrojet speed often influences the balance between the speed and wetting and rate of drying of mix wetting, is to determine
Determine one of key factor of micropill shaping and particle diameter.
There are two important equilibrium process during preparing micropill in centrifugal granulating：One is moisture is inside material and table
The distribution in face, property of the process with material in itself is relevant, depending on material to the absorbability of moisture, if surface of material moisture
Excessively, then particle diameter is excessive, otherwise then particle diameter is too small or is difficult to shape；The second is the wetting and drying of material, the process and rotating disk
Rotating speed is closely related with Liquid spraying pump hydrojet speed, i.e., when rotary speed is slower, micropill is more long by spraying the time in slurry spraying face,
Or during Liquid spraying pump hydrojet speed, dry materials speed is less than wetting speed, surface of material accumulation excess moisture, so as to easily gather
Knot forms bulky grain, conversely, can not then provide enough bonding forces, micropill is difficult to shape.
Liquid spraying pump hydrojet speed being established through experiment and being set as that 200~500ml/min is relatively reasonable, initial speed is 200ml/
Min, the hydrojet speed of Liquid spraying pump is increased then as the continuous addition of material until no longer being added after 500ml/min.
3rd, spray gun atomization condition：
Spray gun atomization condition includes whiff pressure and spray air flow, its atomizing effect and material that can directly affect hydrojet
Wetted uniformity, so as to influence shaping and the particle diameter distribution size of micropill；Increase whiff pressure, it is possible to increase atomization face, makes
Mix wetting is uniform, but whiff pressure it is excessive when, then material is largely flown upward, cause loss of material.Have in control adhesive
On the premise of preferable atomizing effect, should trying one's best, (whiff pressure should be in 0.2~0.25MPa, in conditions permit for reduction spray air flow
In the range of it is as higher as possible).
4th, for powder speed：
The particle diameter of micropill is also had a significant effect for powder speed.For powder speed it is slower when, micropill surface moisture is more, between micropill
Easily coalesce, and form bulky grain, and micropill speed of production is slow, time-consuming, and during for powder excessive velocities, fine powder increases, when viscous
After mixture is sprayed into, particle is polymerized between fine powder, easily forms " pseudonucleus ", while easily cause fine powder flying upward, cause the waste of material.Ying He
The regulation of reason, while adjusting spouting velocity, just can guarantee that the quality and yield of micropill for the speed of powder.
According to the actual conditions that Tilmicosin micropill is produced, it is set as 400g/min for powder velocity original value, with material
The increase of addition is gradually increased for powder speed, until 1000g/min.
5th, air blast flux：
Material moves vertically in the presence of gravity and air blast, therefore improves air blast flux and be conducive to increase material to seethe fortune
Dynamic space and amplitude, are allowed to be difficult to be agglomerated into bulky grain or bulk, but air blast flux is too high, and adhesive makes mix wetting poly-
Gradually dried before knot, be also easy to produce a large amount of fine powders, motion amplitude is excessive while material is seethed, and easily causes the loss of raw material,
Yield is caused to decline.In micropill preparation process, air blast flux is the technological parameter for influenceing drug loss rate most critical.
According to centrifugation pot in material number, the opening degree initial value of air door is set as 100~120m3/ min, after
Phase is enlarged to 220~240m3/min。
6th, polishing time：
Stop supplying powder and whitewashing, but micropill to still need to continue to roll in centrifuge after micropill particle diameter reaches certain requirement
Certain hour, is polished, to improve its mechanical strength and improve its outward appearance proper sphere degree.With the extension of polishing time, micropill
Particle size range narrow, and to small particle shift, show that micropill is broken, small particles increase.Polishing time 4-6min.
Compared with currently a popular extrusion spheronization granulating process, the present invention prepares Tilmicosin intestines using centrifugation pill making craft
Molten micropill has following advantage：
1. process equipment is simple.Centrifugation pill making craft only needs to centrifugation pellet processing machine, classifying screen, three equipment of fluid bed, and
Extrusion spheronization technique needs trough type mixing machine, extruder, circle-throw movement machine, classifying screen, five equipment of fluid bed, by contrast, centrifugation
Pill making craft is more convenient, and occupancy hall space is few, and cost is lower；
2. the micropill particle of centrifugation pill making craft is gradually amplified by the way of powder deposition and formed, and the particle made is very
Uniformly with densification, proper sphere degree is very high, and the spherical shape of standard is presented under the microscope.And extrusion spheronization technique is because by equipment limit,
Material elder generation wet-mixing is made softwood, and then extrusion is in noodles shape, then through shot-blasting machine cut-out and micropill that is round as a ball, being finally made
Grain is presented the slightly sharp similar rice shape (Fig. 3) in two because of process characteristic, and proper sphere degree is not so good as the particle that centrifugation pill making craft is made,
And proper sphere degree particle higher coating efficiency in fluid bed is far above irregular particle；Extrusion spheronization granule coating efficiency
Difference, the coating became uneven of particle surface is even, it is oral after be easily degraded and absorbed in stomach, stomach formed stimulate (be coated with
Grain requires not dissolved in stomach, is dissolved in enteron aisle).
3. it is applied widely to medicine working properties without particular/special requirement, it is applicable not only to general chemicals, Er Qieke
For micropill that is larger containing sugar micropill high and viscosity, cannot being prepared using extrusion spheronization method.
4. solve extrusion spheronization technique again while micropill higher mechanical strength is kept and cause particle by more high-strength
The extruding of degree and be difficult to the problems such as being completely dissolved release, cause most of bulk drug to exclude external, cause environmental pollution.
Test result indicate that, the Tilmicosin enteric-coated micro-pill envelop rate that the present invention is provided is high, can well cover and be examined for rice
The bitter taste of star, and dissolution in intestinal environment is all in, can be used as enteric slow release reagent, it is bad anti-that solution absorption band in stomach comes
Should, its preparation process is simple, raw material is cheap and easy to get, is adapted to industrialization large-scale production, therefore its application prospect is very wide.
Brief description of the drawings
Fig. 1 is Tilmicosin enteric-coated micro-pill particle microgram prepared by present invention process；
Fig. 2 is Tilmicosin micropill particle microgram prepared by intra-liquid desiccation method；Intra-liquid desiccation method full name is in emulsification-liquid
Seasoning, belongs to one kind of method for preparing microsphere, is a kind of known pill method；
Fig. 3 is to extrude Tilmicosin micropill microgram prepared by granulation；
Fig. 4 is the solubility test of Tilmicosin enteric-coated micro-pill of the present invention, and left side is gastric juice, and right side is intestinal fluid.
Specific embodiment
Further detailed, complete explanation is made to the present invention with reference to embodiment.
Embodiment 1
Each raw material is weighed according to the finished product containing following mass percent：
Tilmicosin：23.3%；
Adhesive：20% (being configured to 40% sucrose solution)；
Microcrystalline cellulose：17.2%；
Cornstarch：24.5%；
Coating Solution：Using 30% polyacrylic acid resin emulsion, coating solution is prepared by weight gain 15% is made.
Microcrystalline cellulose was each crushed with cornstarch respectively after 80 mesh sieves plus powder that Tilmicosin must be well mixed
Material, then takes 5Kg powders and is gradually added into centrifugation pellet processing machine, while unlocking turntable and gradually spraying into binder solution, initially leads
Machine rotating speed 100r/min, hydrojet speed 200ml/min, for powder speed 400g/min, door opening is 100m3/min；Time holds
Continuous 6-8min, forms the particle masterbatch of 60~80 mesh.Then the powder for being mixed toward gained before continuous addition in centrifugation pellet processing machine,
It is set as 400g/min for powder velocity original value, as the increase of material addition is gradually increased until 1000g/min；Rotating disk
Initial speed is arranged on 100r/min, is gradually increased to 180r/min；And constantly penetrating binder solution carries out pill；Liquid spraying pump
Initial hydrojet speed is set as 200ml/min, as the increase of material addition is gradually increased to 500ml/min；Liquid spraying pump sprays
Atmospheric pressure 0.2-0.25MPa；The opening degree initial value of air door is set as 100~120m3/ min, the later stage is enlarged to 220~
240m3/min；Stop pill operation when 30 mesh above particles account for 10%；Material particles to be confirmed keep reaching 30 substantially
After the fineness of~60 mesh, pour out material and be placed in 50~55 DEG C of dryings in fluid bed, after the completion of took out 30~60 mesh sieves；It is placed in again
Carry out bottom spray in fluid bed to be coated, the polyacrylic acid resin emulsion that penetrating is prepared, final sieving obtains Tilmicosin enteric
Micropill finished product.Centrifugation pellet processing machine is that WL-1000 types are centrifuged pellet processing machine, limited purchased from the rising sun pharmaceutical machine device fabrication of section of Chongqing City
Company.(similarly hereinafter)
Embodiment 2
Each raw material is weighed according to the finished product containing following mass percent：
Tilmicosin：25.8%；
Adhesive：15% (being configured to 40% sucrose solution)；
Microcrystalline cellulose：24.2%；
Cornstarch：20%；
Coating Solution：Using 40% polyacrylic acid resin emulsion, coating solution is prepared by weight gain 15% is made.
Microcrystalline cellulose was each crushed with cornstarch respectively after 80 mesh sieves plus powder that Tilmicosin must be well mixed
Material, then takes during 5Kg powders add centrifugation pellet processing machine, while unlocking turntable and binder solution is gradually sprayed into, Initial master turn
Fast 100r/min, hydrojet speed 200ml/min, for powder speed 400g/min, door opening is 100~120m3/min；Time holds
Continuous 6-8min, forms the particle masterbatch of 60~80 mesh.Then the powder for being mixed toward gained before continuous addition in centrifugation pellet processing machine,
It is set as 400g/min for powder velocity original value, as the increase of material addition is gradually increased until 1000g/min；Rotating disk
Initial speed is arranged on 100r/min, is gradually increased to 180r/min；And constantly penetrating binder solution carries out pill；Liquid spraying pump
Initial hydrojet speed is set as 200ml/min, as the increase of material addition is gradually increased to 500ml/min；Liquid spraying pump sprays
0.2~0.25MPa of atmospheric pressure；The opening degree initial value of air door is set as 100~120m3/ min, the later stage is enlarged to 220~
240m3/min；Stop pill operation when 30 mesh above particles account for 10%；Material particles to be confirmed keep reaching 30 substantially~
After the fineness of 60 mesh, pour out material and be placed in 50~55 DEG C of dryings in fluid bed, after the completion of took out 30~60 mesh sieves；Stream is placed in again
Carry out bottom spray in change bed to be coated, the polyacrylic acid resin emulsion that penetrating is prepared, finally sieving, it is micro- to obtain Tilmicosin enteric
Ball finished product.
Embodiment 3
Method according to embodiment 1 carries out morphology investigation, the measure of drugloading rate, envelop rate to gained micropill finished product
Measure and dissolution release experiment under various circumstances；Result shows that the Tilmicosin enteric-coated micro-pill of present invention offer is in 30
~60 mesh spheroidal micropills, proper sphere degree is high, and granule size is uniform (see Fig. 1), drugloading rate 20~25%, and with dosage phase
When envelop rate is 100%.The micropill that extruding granulation is produced is spherical irregular, and granule size heterogeneity (see Fig. 3) carries medicine
Amount is in 20~25%, encapsulating uneven thickness one suitable with dosage.The micropill that intra-liquid desiccation method is formed is elliposoidal, granularity
Size is uneven, (see Fig. 2), and 20~25%, suitable with dosage, the micropill prepared by intra-liquid desiccation method is not wrapped drugloading rate
Quilt.
Embodiment 4：Alimentary canal dissolution experiment
Digestion liquid making method
The main component and acid-base value of gastric juice and intestinal fluid are as shown in table 1 below, and 2L gastric juice and intestinal fluid are prepared respectively, required
Material mass such as following table.Gastric juice debugs pH using the hydrochloric acid of 1M, and intestinal fluid debugs pH with 1M NaOH.
Table 1
| NaCl | KCl | pH | |||
| Gastric juice | 10.36 | 0.98 | - | - | 2.0 |
| Intestinal fluid | 11.55 | 2.45 | 40.96 | 8.32 | 6.44 |
Solubility test
Four 200ml triangular flasks are taken respectively, and numbering is respectively A, B, C, D, and gastric juice 100ml, triangle are added in triangular flask A, C
Intestinal fluid 100ml is added in bottle B, D；Tilmicosin enteric-coated micro-pill prepared by the 4g present invention, triangle are added in triangular flask A, B respectively
4g extruding granulation Tilmicosins are added in bottle C, D respectively, A, B, C, D shake dissolving in 37 DEG C of shaking tables simultaneously, and rotating speed is 40r/
Min, SGF and intestinal fluid.Per observing dissolving situation every other hour and taking pictures, filtered after 4h, obtain filtered fluid.Using height
Effect liquid phase chromatogram method determines the Tilmicosin content dissolved in digestive juice, and calculates dissolving percentage.
Interpretation of result
Table 2
| Numbering | Test sample | Reaction solution | Reaction time (h) | Dissolving percentage (%) |
| A | Centrifugal granulator Tilmicosin | Gastric juice | 4 | 1.98 |
| B | Centrifugal granulator Tilmicosin | Intestinal fluid | 4 | 43.98 |
| C | Extruding granulation Tilmicosin | Gastric juice | 4 | 3.83 |
| D | Extruding granulation Tilmicosin | Intestinal fluid | 4 | 42.46 |
By in upper table 2, the Tilmicosin prepared by the present invention extrudes granulation for 1.98% for rice in the solubility of gastric juice
It is 3.83% that star is examined in the solubility of gastric juice；Dissolving of the prepared Tilmicosin of the invention than extruding granulation Tilmicosin under one's belt
Degree is low, it is possible to reduce damage of the Tilmicosin to gastric mucosa；And both solubility in intestinal fluid are more or less the same.
Figure 4, it is seen that solubility very little of the coating type Tilmicosin enteric-coated micro-pill of the present invention in gastric juice, and
Solubility in intestinal fluid is very big, and intestinal fluid becomes cloudy.Show, dissolution is extremely low in gastric juice environment, the dissolution in intestinal juice environment
Completely.
Embodiment 5
Influence of the Tilmicosin enteric-coated micro-pill of the present invention to pig feed intake
Test site and time
Yueyang large-scale pig farm, in December, 2014.
Test method and step
Experimental animal is selected
Age in days is identical, in the same size for selection, well-grown child care pig as experimental animal, record the age in days of animal, with
Machine is divided into three groups, and numbering is respectively A, B, C.
Processing method
Three groups of child care pigs are fed using identical child care material, are set to addition group of the present invention, intra-liquid desiccation method and are examined for rice
Star addition group, blank control group, addition are as shown in table 3.
The experimental animal medicine addition of table 3
Animal is weighed
Experimental animal is weighed on an empty stomach before and after experiment, obtains on-test average weight and the last average weight of experiment.
Feed intake is recorded
Three groups of child care swine rearing management conditions are consistent, free choice feeding, free water, and experiment number of days is 7 days.Record every group it is every
It total feed intake.
The feed intake experimental result statistical form of table 4
| Group | A | B | C |
| Experiment starts age in days | 35 days | 35 days | 35 days |
| Average weight before experiment | 11.3kg | 11.5kg | 11.4 |
| Average weight after experiment | 14.3kg | 14.1kg | 14.5 |
| Average daily gain | 428g/ days | 371g/ days | 442g/ days |
| Average daily gain (g) | 668g | 602g | 670g |
Result of the test and analysis
Result shows that enteric solubility Tilmicosin group (A groups) average daily gain of the present invention is 668g during experiment, is not coated with
Tilmicosin group (B groups) average daily gain is 602g, and the average daily gain of control group is 670g.Result shows fluid drying
Method Tilmicosin can reduce the feed intake of pig, and feed intake influence of the enteric solubility Tilmicosin of the present invention on pig is little.
Finally be necessary described herein be：Above example is served only for making further in detail technical scheme
Ground explanation, it is impossible to be interpreted as limiting the scope of the invention, those skilled in the art's the above of the invention
Some the nonessential modifications and adaptations made belong to protection scope of the present invention.
Claims (3)
1. a kind of centrifugal process prepares Tilmicosin enteric-coated micro-pill technique, it is characterised in that by the group of following weight percent content
It is grouped into：Tilmicosin 21~26%, cornstarch 20~25%, adhesive 10~20%, the and of microcrystalline cellulose 23~30%
Coating material 10~20%；Described adhesive is selected from one or more the mixing in sucrose, HPMC, fructose
Thing；
What is prepared comprises the following steps that：
A) cornstarch, microcrystalline cellulose sieving, screen cloth is 80 mesh, weighs cornstarch, microcrystalline cellulose, adds Tilmicosin
It is well mixed after former powder, obtains powder；
B) 4~6Kg powders, rotary speed is added to be set as 90~110r/min, Liquid spraying pump spray in the rotating disk of centrifugation pellet processing machine
Liquid speed degree is set as 180~200ml/min, and door opening is 100~120m3/min；Rotating disk and air feed are then turned on, powder exists
Lifted up in rotation process, and constantly rolled under baffle effect, Liquid spraying pump spray into adhesive make powder fine-powder it
Between mutually bond, the time continues 6~8min, forms the particle masterbatch of 60~80 mesh；
C) powder mixed toward continuous addition step a) gained in centrifugation pellet processing machine, 400g/ is set as powder velocity original value
Min, 1000g/min is gradually increased to for powder speed；The initial speed of rotating disk is arranged on 100r/min, is gradually increased to 180r/
min；And constantly penetrating binder solution carries out pill；The initial hydrojet speed of Liquid spraying pump is set as 200ml/min, with material plus
The increase for entering amount is gradually increased to 500ml/min；0.2~0.25MPa of Liquid spraying pump whiff pressure；The opening degree initial value of air door
It is set as 100~120m3/ min, the later stage is enlarged to 220~240m3/min；Stop system when 30 mesh above particles account for 10%
Ball is operated；Stop for after powder and whitewashing, particle still needs to continue to roll in centrifugation pellet processing machine be polished for 4~6 minutes；
D) particle that step c) is obtained is placed in fluid bed and is dried two hours with 50~55 DEG C of state, take out sieving, obtained
The particle of 30~60 mesh；
E) particle obtained by step d) is sprayed into Coating Solution to be coated, described Tilmicosin enteric is obtained final product after sieving micro-
Ball；Described Coating Solution is polyacrylic acid resin emulsion.
2. centrifugal process according to claim 1 prepares Tilmicosin enteric-coated micro-pill technique, it is characterised in that during using sucrose
Be formulated as 40% aqueous solution, during using HPMC obtained aqueous solution concentration be 3%, using fructose when prepare water-soluble
Liquid concentration is 50%.
3. centrifugal process according to claim 1 prepares Tilmicosin enteric-coated micro-pill technique, it is characterised in that the polypropylene
Acid resin latax concentration is 30%.
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| CN107375247B (en) * | 2017-08-25 | 2020-05-26 | 重庆市畜牧科学院 | Tilmicosin film-controlled enteric sustained-release preparation and preparation method thereof |
| CN108478588B (en) * | 2018-04-26 | 2020-12-18 | 江西派尼生物药业有限公司 | Tilmicosin slow-release enteric solvent and preparation method thereof |
| CN109364042B (en) * | 2018-11-26 | 2021-04-02 | 河北地邦动物保健科技有限公司 | Traditional Chinese medicine targeted tilmicosin micro-pill and preparation method thereof |
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| US20050169966A1 (en) * | 2000-06-08 | 2005-08-04 | Ivy Animal Health, Inc. | Growth promoting pharmaceutical implant |
| CN102068412A (en) * | 2011-01-21 | 2011-05-25 | 黑龙江大学 | Enteric targeted tilmicosin particles and preparation method thereof |
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| US20050169966A1 (en) * | 2000-06-08 | 2005-08-04 | Ivy Animal Health, Inc. | Growth promoting pharmaceutical implant |
| CN102068412A (en) * | 2011-01-21 | 2011-05-25 | 黑龙江大学 | Enteric targeted tilmicosin particles and preparation method thereof |
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| 替米考星微丸肠溶包衣的处方筛选;赵林，等;《中国兽药杂志》;20111231;第45卷(第6期);第5-7页"仪器与试药"部分和"2方法与结果"部分 * |
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