CN108653243B - A kind of preparation method being sustained Tilmicosin microcapsule powder - Google Patents

A kind of preparation method being sustained Tilmicosin microcapsule powder Download PDF

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CN108653243B
CN108653243B CN201810289803.1A CN201810289803A CN108653243B CN 108653243 B CN108653243 B CN 108653243B CN 201810289803 A CN201810289803 A CN 201810289803A CN 108653243 B CN108653243 B CN 108653243B
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tilmicosin
microcapsule powder
stirring
preparation
obtains
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CN108653243A (en
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张笑意
朱崇淼
韩斌
吴肖
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JIANGSU NANNONG HI-TECH ANIMAL MEDICINE Co Ltd
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JIANGSU NANNONG HI-TECH ANIMAL MEDICINE Co Ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5036Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/501Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5026Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5036Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents

Abstract

It is first that acrylic acid is soluble in water the invention discloses a kind of preparation method for being sustained Tilmicosin microcapsule powder, pH value of solution is adjusted to neutrality, then starch and hydroxypropyl methylcellulose is added, heat up stirring and dissolving, adds Tilmicosin raw material and calcium chloride, is stirred to obtain mixed solution one;Then polyethylene glycol and Sodium Polyacrylate are added in mixed solution one, is carried out by homogenizer high-pressure homogeneous after stirring and dissolving, obtains homogenizing fluid;Sodium alginate aqueous solution is instilled in homogenizing fluid under agitation again, and continues stirring 40-50 minutes, obtains mixed liquor;Finally mixed liquor is dried, obtains sustained release Tilmicosin microcapsule powder.The microcapsule powder that method provided by the invention obtains has good taste masking effect, and the slow release effect with the long period, higher blood concentration can be kept for a long time in stomach, intestines environment, improves curative effect.

Description

A kind of preparation method being sustained Tilmicosin microcapsule powder
Technical field
The invention belongs to pharmaceutical fields, and in particular to a kind of preparation method for being sustained Tilmicosin microcapsule powder.
Background technique
Tilmicosin (Tilmicosin) is that a kind of newer macrolides livestock and poultry semi-synthetic by tylosin are dedicated Antibiotic, the eighties are succeeded in developing by Elanco Animal Health Care Products Corporation, Britain.Since its special antibacterial activity and medicine are dynamic Feature is learned, which has gone through the prevention and treatment for being clinically used for the animal infectious diseases such as ox, goat, sheep, milk cow, pig, chicken, especially It is livestock and birds respiratory disease, such as domestic animal Actinobacillus property pleuropneumonia, pasteurellosis and gallisepticum chicken disease and lactating mammal The treatment of mammitis.
Tilmicosin has with tylosin similar broad spectrum antibiotic activity, to gram-positive bacteria and certain gram-negatives Property bacterium, Mycoplasma, conveyor screw etc. have inhibiting effect, have Actinobacillus pleuropneumoniae, Pasteurella and Mycoplasma than Thailand The happy stronger antibacterial activity of rhzomorph.Since Tilmicosin is very bitter, and it is odorous, when spice is fed, on the one hand it will affect agreeable to the taste Property, it is on the other hand irritating to the stomach of animal, it causes vomiting when serious or even some animals smells the taste of Tilmicosin It is unwilling to just feed, seriously affect the popularization and application of Tilmicosin.
Summary of the invention
It is an object of the invention to provide a kind of sustained release Tilmicosin micro-capsule to overcome the above the deficiencies in the prior art The preparation method of powder improves sustained release performance of the Tilmicosin as drug while taste masking fine to Tilmicosin so that its In stomach and intestines can sustained release, maintain high blood concentration for a long time.
Technical scheme is as follows:
A kind of preparation method being sustained Tilmicosin microcapsule powder, comprising the following steps:
Step 1, acrylic acid is soluble in water, pH value of solution is adjusted to neutrality, and starch and hydroxypropyl methylcellulose is then added, rises Warm stirring and dissolving adds Tilmicosin raw material and calcium chloride, is stirred to obtain mixed solution one;
Step 2, polyethylene glycol and Sodium Polyacrylate are added in mixed solution one, is carried out after stirring and dissolving by homogenizer It is high-pressure homogeneous, obtain homogenizing fluid;
Step 3, sodium alginate aqueous solution is instilled in homogenizing fluid under stirring condition, and continues stirring 40-50 minutes, obtained Mixed liquor;
Step 4, mixed liquor is dried, obtains sustained release Tilmicosin microcapsule powder.
Further, the preparation method of the described sustained release Tilmicosin microcapsule powder, acrylic resin, starch, hydroxypropyl in step 1 The addition mass ratio of methylcellulose, Tilmicosin raw material and calcium chloride is 10-15:20-30:3-5:20-30:1-2;Mixed solution One solid content is 35-40%.
Further, the warming temperature of the preparation method of the described sustained release Tilmicosin microcapsule powder, the stirring that heats up in step 1 is 50-60℃。
Further, the preparation method of the described sustained release Tilmicosin microcapsule powder, polyethylene glycol is polyethylene glycol in step 2 400。
Further, the preparation method of the described sustained release Tilmicosin microcapsule powder, the addition quality of polyethylene glycol is in step 2 The 0.5-1% of one mass of mixed solution, the addition quality of Sodium Polyacrylate are the 5-8% of one mass of mixed solution.
Further, the preparation method of the sustained release Tilmicosin microcapsule powder, the pressure of step 2 mesohigh homogeneous are 30- 40MPa。
Further, the preparation method of the described sustained release Tilmicosin microcapsule powder, seaweed in sodium alginate aqueous solution in step 3 The mass percent concentration of sour sodium is 10-15%.
Further, the preparation method of the described sustained release Tilmicosin microcapsule powder, sodium alginate aqueous solution additional amount in step 3 Mass ratio with homogenizing fluid is 1:2.
Further, the preparation method of the described sustained release Tilmicosin microcapsule powder, the mixing speed of stirring condition is in step 3 200-250 revs/min.
The present invention is basic auxiliary material using acrylic acid, starch and hydroxypropyl methylcellulose, is adjusted to neutrality pH value of solution early period, The aqueous solution that stable similar colloid character is made up of acrylic acid, starch and hydroxypropyl methylcellulose, can promote Tilmicosin Raw material is preferably dispersed in mixed solution.
The present invention adjusts microcapsules using polyethylene glycol and Sodium Polyacrylate and forms, so that final microcapsule powder is in Gastric pH ring It is easier to swelling in border and releases Tilmicosin.
In the present invention introduce calcium chloride purpose be with sodium alginate generate part crosslinked action, calcium chloride acrylic acid, It is sufficiently dissolved in the base soln of starch and hydroxypropyl methylcellulose composition, calcium ion is filled into homogenizing fluid in homogenizing process In nanosphere, so that calcium ion generates passivation effect, the effect of delayed cross-linking is generated to the addition of subsequent sodium alginate, gradually It being formed in microsphere surface and is crosslinked incomplete inclusion enclave, the wrapping layer is non-swelling in Gastric pH environment, and in small intestinal pH environment In it is soluble and discharge drug, therefore sustained release Tilmicosin microcapsule powder provided by the invention utilizes poly- second two in gastric juice environment The adjustment effect of pure and mild Sodium Polyacrylate is partly dissolved it well, discharges drug, and cross-linked layer dissolves in intestines environment, The effect of sustained release drugs is generated, and then higher blood concentration can be maintained within the very long duration.
The sustained release Tilmicosin microcapsule powder that method provided by the invention obtains, can be obtained by blood concentration and Drug-time curve Out, the high value of blood concentration can be reached after average 1h, and continues higher blood concentration and is able to maintain that about 12h, simultaneously Blood concentration relative drop is slow in subsequent metabolic process, and whole process blood concentration maintains more stable state, Peak value fluctuation less, can be good at continuing to play drug effect.
The sustained release Tilmicosin microcapsule powder that method provided by the invention obtains has good taste masking effect, passes through homogeneous The crosslinked action of emulsification and sodium alginate, so that finally obtained microcapsule powder can be good at for Tilmicosin being wrapped in Inside masks bad smell well, improves palatability, additionally, due to drug in stomach and intestine slow sustained release, and release It is relatively steady to let off journey, reduces medicine irritation.
Specific embodiment:
Embodiment 1
A kind of preparation method being sustained Tilmicosin microcapsule powder, comprising the following steps:
Step 1,200g acrylic acid is dissolved in 1700g water, adjusts pH value of solution to neutrality, be then added 400g starch and 60g hydroxypropyl methylcellulose is warming up to 50 DEG C, and stirring and dissolving adds 400g Tilmicosin raw material and 20g calcium chloride, and stirring is mixed Conjunction obtains mixed solution one;
Step 2,10.9g polyethylene glycol 400 and 109g Sodium Polyacrylate are added in mixed solution one, leads to after stirring and dissolving Cross homogenizer carry out it is high-pressure homogeneous, homogenization pressure 30MPa obtains homogenizing fluid;
Step 3, the seaweed for being 10% by mass percent concentration under the stirring condition that low whipping speed is 200 revs/min Acid sodium aqueous solution 1450g is instilled in homogenizing fluid, and continues stirring 40 minutes, obtains mixed liquor;
Step 4, mixed liquor is spray-dried, the intake air temperature of spray drying is 180 DEG C, air outlet temperature 80 DEG C, obtain sustained release Tilmicosin microcapsule powder.
Embodiment 2
A kind of preparation method being sustained Tilmicosin microcapsule powder, comprising the following steps:
Step 1,250g acrylic acid is dissolved in 2522g water, adjusts pH value of solution to neutrality, be then added 500g starch and 80g hydroxypropyl methylcellulose is warming up to 53 DEG C, and stirring and dissolving adds 500g Tilmicosin raw material and 28g calcium chloride, and stirring is mixed Conjunction obtains mixed solution one;
Step 2,31g polyethylene glycol 400 and 232.8g Sodium Polyacrylate are added in mixed solution one, leads to after stirring and dissolving Cross homogenizer carry out it is high-pressure homogeneous, homogenization pressure 35MPa obtains homogenizing fluid;
Step 3, the seaweed for being 12% by mass percent concentration under the stirring condition that low whipping speed is 230 revs/min Acid sodium aqueous solution 2072g is instilled in homogenizing fluid, and continues stirring 45 minutes, obtains mixed liquor;
Step 4, mixed liquor is spray-dried, the intake air temperature of spray drying is 185 DEG C, air outlet temperature 80 DEG C, obtain sustained release Tilmicosin microcapsule powder.
Embodiment 3
A kind of preparation method being sustained Tilmicosin microcapsule powder, comprising the following steps:
Step 1,280g acrylic acid is dissolved in 2455g water, adjusts pH value of solution to neutrality, be then added 550g starch and 70g hydroxypropyl methylcellulose is warming up to 57 DEG C, and stirring and dissolving adds 570g Tilmicosin raw material and 35g calcium chloride, and stirring is mixed Conjunction obtains mixed solution one;
Step 2,39.6g polyethylene glycol 400 and 277g Sodium Polyacrylate are added in mixed solution one, leads to after stirring and dissolving Cross homogenizer carry out it is high-pressure homogeneous, homogenization pressure 40MPa obtains homogenizing fluid;
Step 3, the seaweed for being 13% by mass percent concentration under the stirring condition that low whipping speed is 240 revs/min Acid sodium aqueous solution 2138g is instilled in homogenizing fluid, and continues stirring 48 minutes, obtains mixed liquor;
Step 4, mixed liquor is spray-dried, the intake air temperature of spray drying is 190 DEG C, air outlet temperature 85 DEG C, obtain sustained release Tilmicosin microcapsule powder.
Embodiment 4
A kind of preparation method being sustained Tilmicosin microcapsule powder, comprising the following steps:
Step 1,300g acrylic acid is dissolved in 2460g water, adjusts pH value of solution to neutrality, be then added 600g starch and 100g hydroxypropyl methylcellulose is warming up to 60 DEG C, and stirring and dissolving adds 600g Tilmicosin raw material and 40g calcium chloride, and stirring is mixed Conjunction obtains mixed solution one;
Step 2,41g polyethylene glycol 400 and 328g Sodium Polyacrylate are added in mixed solution one, passes through after stirring and dissolving Homogenizer progress is high-pressure homogeneous, and homogenization pressure 40MPa obtains homogenizing fluid;
Step 3, the seaweed for being 15% by mass percent concentration under the stirring condition that low whipping speed is 250 revs/min Acid sodium aqueous solution 2234.5g is instilled in homogenizing fluid, and continues stirring 50 minutes, obtains mixed liquor;
Step 4, mixed liquor is spray-dried, the intake air temperature of spray drying is 190 DEG C, and air outlet temperature is 100 DEG C, obtain sustained release Tilmicosin microcapsule powder.
Pharmacodynamics test is carried out using the sustained release Tilmicosin microcapsule powder that above embodiments are prepared, chooses Nanjing branch The serious pig farm of pathogen infection carries out clinical verification test.The swinery of infection is mainly shown as that morning intermittence is coughed, and chooses 60 suffer from the infected pig of the above cough symptom, are randomly divided into two groups, every group 30, feed what the present invention was prepared respectively It is sustained Tilmicosin microcapsule powder and commercially available Tilmicosin pre-mixing agent, each Feeding time is identical as main ingredient amount is fed, and continuously feeds Pig cough head number in observation every morning 1h, as a result see the table below after six days, six days.
By result above as can be seen that being fed after dosage feeds six days identical, Tilmicosin microcapsule powder of the present invention Therapeutic effect is significant, is capable of the cough quantity of significant less infection pig, cough phenomenon was eaten at the 9th day and is disappeared substantially, using effect Significantly.
The performance of the preparation method and obtained sustained release Tilmicosin microcapsule powder that provide in order to better illustrate the present invention Feature, spy carry out test comparison from following several respects reference examples.
Reference examples 1
A kind of preparation method being sustained Tilmicosin microcapsule powder, comprising the following steps:
Step 1,280g acrylic acid is dissolved in 2455g water, adjusts pH value of solution to neutrality, be then added 550g starch and 70g hydroxypropyl methylcellulose is warming up to 57 DEG C, and stirring and dissolving adds 570g Tilmicosin raw material and 35g calcium chloride, and stirring is mixed Conjunction obtains mixed solution one;
Step 2, mixed solution one is carried out by homogenizer high-pressure homogeneous, homogenization pressure 40MPa obtains homogenizing fluid;
Step 3, the seaweed for being 13% by mass percent concentration under the stirring condition that low whipping speed is 240 revs/min Acid sodium aqueous solution 2138g is instilled in homogenizing fluid, and continues stirring 48 minutes, obtains mixed liquor;
Step 4, mixed liquor is dried, obtains sustained release Tilmicosin microcapsule powder.
Reference examples 2
A kind of preparation method being sustained Tilmicosin microcapsule powder, comprising the following steps:
Step 1,280g acrylic acid is dissolved in 2455g water, adjusts pH value of solution to neutrality, be then added 550g starch and 70g hydroxypropyl methylcellulose is warming up to 57 DEG C, and stirring and dissolving adds 570g Tilmicosin raw material and 35g calcium chloride, and stirring is mixed Conjunction obtains mixed solution one;
Step 2,39.6g polyethylene glycol 400 and 277g Sodium Polyacrylate are added in mixed solution one, leads to after stirring and dissolving Cross homogenizer carry out it is high-pressure homogeneous, homogenization pressure 40MPa obtains homogenizing fluid;
Step 3, homogenizing fluid is spray-dried, the intake air temperature of spray drying is 190 DEG C, air outlet temperature 85 DEG C, obtain sustained release Tilmicosin microcapsule powder.
Reference examples 3
A kind of preparation method being sustained Tilmicosin microcapsule powder, comprising the following steps:
Step 1,830g starch and 70g hydroxypropyl methylcellulose are added in 2455g water, are warming up to 57 DEG C, stirring and dissolving, 570g Tilmicosin raw material and 35g calcium chloride are added, is stirred to obtain mixed solution one;
Step 2,39.6g polyethylene glycol 400 and 277g Sodium Polyacrylate are added in mixed solution one, leads to after stirring and dissolving Cross homogenizer carry out it is high-pressure homogeneous, homogenization pressure 40MPa obtains homogenizing fluid;
Step 3, the seaweed for being 13% by mass percent concentration under the stirring condition that low whipping speed is 240 revs/min Acid sodium aqueous solution 2138g is instilled in homogenizing fluid, and continues stirring 48 minutes, obtains mixed liquor;
Step 4, mixed liquor is dried, obtains sustained release Tilmicosin microcapsule powder.
The microcapsule powder that above embodiments 3 and reference examples 1-3 are obtained carries out pharmacodynamic experiment, while former using Tilmicosin Expect medicine as a comparison case, pig 50 for choosing 25-30kg or so are tested, and stochastic averagina is divided into 5 groups, take unified feeding side Formula carries out feeding one week, then unifies fasting progress stomach-filling in 12 hours, disposably fills according to the Tilmicosin bulk pharmaceutical chemicals of 80mg/kg Stomach comparative example group, using Tilmicosin microcapsule powder stomach-filling embodiment group identical after conversion and reference examples group, after stomach-filling respectively at 0.5h, 1h, 2h, 4h, 6h, 12h, 18h, for 24 hours, 36h, 48h, 72h and 96h acquisition peripheric venous blood in anticoagulant tube, separate blood Slurry, according to document, (Lee is deposited, and HPLC detection method of the Tilmicosin in porcine tissue and excreta and its grinds in pig Internal pharmacokinetics Study carefully, [D], China Agricultural University, 2003.) in method be measured and calculate blood concentration, every group is averaged, and is specifically shown in Following table:
Time (h) Comparative example Embodiment 3 Reference examples 1 Reference examples 2 Reference examples 3
0 0 0 0 0 0
0.5 1.05 0.95 0.89 1.02 0.35
1 2.89 2.46 1.36 2.83 0.67
2 3.86 3.15 2.05 3.73 1.37
4 4.45 3.56 3.06 3.97 2.58
6 2.21 3.52 3.88 2.55 3.36
12 1.05 2.74 2.89 1.66 3.52
18 0.56 2.36 2.66 0.88 3.12
24 0.41 1.78 1.81 0.67 1.82
36 0.08 1.56 1.45 0.58 1.52
48 0.03 1.24 1.26 0.42 1.27
72 0.02 0.83 0.91 0.31 0.93
96 0.01 0.57 0.63 0.22 0.58
From the above, it can be seen that the Tilmicosin microcapsule powder that the preparation method that the present invention improves obtains, has longer blood Concentration is held time, and as shown in 3 result of embodiment, after medicine enters stomach, 1h or so blood concentration can reach higher degree, Blood concentration can maintain in higher range in 1-18h, and the lifting of whole process blood concentration is more gentle, can The effect of constant drug effect is played well;Comparative example is to directly adopt Tilmicosin bulk pharmaceutical chemicals to compare, it can be seen that raw material Medicine has quickly reached the peak value of blood concentration, and blood concentration is decreased obviously after 6h, and blood concentration is held time shorter, medicine It is poor to imitate duration.
Polyethylene glycol 400 and Sodium Polyacrylate is added to be no on the basis of embodiment 3 in reference examples 1, it can be seen that Blood concentration has just reached higher peak value section after 4h is administered, and illustrates that the dissolubility of its drug under one's belt is poor, mainly It concentrates in small intestine carrying out the dissolution and absorption of drug.
Reference examples 2 be on the basis of embodiment 3 without be added sodium alginate aqueous solution be crosslinked, as a result it can be seen that Drug has just reached peak value in 4h, and blood concentration peak section concentrates on 1-6h, and it is more complete to illustrate that it has just been carried out under one's belt Full drug dissolution.
That acrylic acid is not added and adjusts pH value of solution in reference examples 3, the amount that acrylic acid is added is replaced with starch, was being prepared Cheng Zhong is crosslinked ball after sodium alginate aqueous solution is added, in mixed liquor and increases obviously, and volume is larger, and the variation of homogenizing fluid character is bright It is aobvious, and in the pharmacodynamic experiment in later period, table as above, early period, dissolubility was poor, started to occur preferably dissolving and inhaling after 4h Receive, main cause be calcium ion and sodium alginate cross-linking degree are big in preparation process early period, form significantly be crosslinked it is spherical Gel, the formation of the gel is unfavorable for the dissolution of drug under one's belt, and is easier to dissolve and absorb in small intestine.

Claims (4)

1. a kind of preparation method for being sustained Tilmicosin microcapsule powder, which comprises the following steps:
Step 1, acrylic acid is soluble in water, pH value of solution is adjusted to neutrality, and starch then is added and hydroxypropyl methylcellulose, heating are stirred Dissolution is mixed, Tilmicosin raw material and calcium chloride are added, is stirred to obtain mixed solution one;
Step 2, it is added polyethylene glycol and Sodium Polyacrylate in mixed solution one, high pressure is carried out by homogenizer after stirring and dissolving Homogeneous obtains homogenizing fluid;
Step 3, sodium alginate aqueous solution is instilled in homogenizing fluid under stirring condition, and continues stirring 40-50 minutes, mixed Liquid;
Step 4, mixed liquor is dried, obtains sustained release Tilmicosin microcapsule powder;
Acrylic resin in step 1, starch, hydroxypropyl methylcellulose, Tilmicosin raw material and calcium chloride addition mass ratio be 10- 15:20-30:3-5:20-30:1-2, the solid content of mixed solution one are 35-40%;Polyethylene glycol is polyethylene glycol in step 2 400, the addition quality of polyethylene glycol is the 0.5-1% of one mass of mixed solution, and the addition quality of Sodium Polyacrylate is mixed solution The 5-8% of one mass;The mass percent concentration of sodium alginate is 10-15%, sodium alginate in sodium alginate aqueous solution in step 3 The mass ratio of aqueous solution additional amount and homogenizing fluid is 1:2.
2. the preparation method of sustained release Tilmicosin microcapsule powder according to claim 1, which is characterized in that heat up in step 1 The warming temperature of stirring is 50-60 DEG C.
3. the preparation method of sustained release Tilmicosin microcapsule powder according to claim 1, which is characterized in that step 2 mesohigh The pressure of homogeneous is 30-40MPa.
4. the preparation method of sustained release Tilmicosin microcapsule powder according to claim 1, which is characterized in that stirred in step 3 The mixing speed of condition is 200-250 revs/min.
CN201810289803.1A 2018-03-30 2018-03-30 A kind of preparation method being sustained Tilmicosin microcapsule powder Active CN108653243B (en)

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