CN108653243B - A kind of preparation method being sustained Tilmicosin microcapsule powder - Google Patents
A kind of preparation method being sustained Tilmicosin microcapsule powder Download PDFInfo
- Publication number
- 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
- Authority
- CN
- China
- Prior art keywords
- tilmicosin
- microcapsule powder
- stirring
- preparation
- obtains
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules 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
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
-
- 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
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules 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
- A61K9/5005—Wall or coating material
- A61K9/501—Inorganic compounds
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules 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
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules 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
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
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
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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810289803.1A CN108653243B (en) | 2018-03-30 | 2018-03-30 | A kind of preparation method being sustained Tilmicosin microcapsule powder |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810289803.1A CN108653243B (en) | 2018-03-30 | 2018-03-30 | A kind of preparation method being sustained Tilmicosin microcapsule powder |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108653243A CN108653243A (en) | 2018-10-16 |
| CN108653243B true CN108653243B (en) | 2019-03-22 |
Family
ID=63782126
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810289803.1A Active CN108653243B (en) | 2018-03-30 | 2018-03-30 | A kind of preparation method being sustained Tilmicosin microcapsule powder |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108653243B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112494460B (en) * | 2020-12-10 | 2022-03-11 | 浙江大飞龙动物保健品股份有限公司 | Tilmicosin powder and preparation method thereof |
| CN114796108B (en) * | 2022-06-30 | 2022-09-02 | 山东国邦药业有限公司 | Tilmicosin solution and preparation method thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4316488A3 (en) * | 2011-03-23 | 2024-02-28 | Ironshore Pharmaceuticals & Development, Inc. | Methods and compositions for treatment of attention deficit disorder |
| CN103417514B (en) * | 2012-05-24 | 2017-06-16 | 石药集团中奇制药技术（石家庄）有限公司 | A kind of butylphenyl phthaleine pharmaceutical composition of microencapsulation and its production and use |
| CN106176680A (en) * | 2016-08-17 | 2016-12-07 | 广州格雷特生物科技有限公司 | A kind of enteric tilmicosin slow-releasing microcapsule and preparation method thereof |
-
2018
- 2018-03-30 CN CN201810289803.1A patent/CN108653243B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN108653243A (en) | 2018-10-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103083281B (en) | Enteric-coated tilmicosin slow-release micro-capsule preparation and preparation method thereof | |
| CN102670516A (en) | Tilmicosin soluble powder and preparation method thereof | |
| CN102362853B (en) | Genipin cross-linked soybean protein based theophylline controlled-release gel preparation and preparation method thereof | |
| CN108653243B (en) | A kind of preparation method being sustained Tilmicosin microcapsule powder | |
| CN107737106A (en) | Safe ten thousand rhzomorph sol particles of a kind of tartaric acid and preparation method thereof | |
| CN201426856Y (en) | Tilmicosin enteric coated granule | |
| CN106176680A (en) | A kind of enteric tilmicosin slow-releasing microcapsule and preparation method thereof | |
| CN104814931B (en) | A kind of olaquindox slow-releasing granules and its preparation method and application | |
| CN107981351B (en) | Dietary microcapsule particle for regulating body fat rate and preparation method thereof | |
| KR101139372B1 (en) | Method for preparing feed additive and feed additivethere from | |
| CN101106976A (en) | Novel galenic system for active principle transport, preparation method and use | |
| CN103622919A (en) | Tilmicosin phosphate enteric granules and preparation method thereof | |
| CN103652366B (en) | A kind of stabilization micro-capsule coating Mercaptamine and preparation method thereof | |
| CN106176671A (en) | A kind of tasteless tilmicosin granule and preparation method thereof | |
| CN105327334A (en) | Enteric coating pellets for treating piglet diarrhea and preparation method and application thereof | |
| CN107375247B (en) | Tilmicosin film-controlled enteric sustained-release preparation and preparation method thereof | |
| CN108902476A (en) | A kind of sustained release sodium butyrate and preparation method thereof suitable for different livestock and poultry | |
| CN104666250B (en) | A kind of preparation method of aureomycin sustained-release micro-spheres | |
| CN110251481A (en) | A kind of veterinary tilmicosin taste masking slow-releasing granules and its preparation process | |
| CN111034863A (en) | Animal solid soft chewing nutritional preparation and preparation method thereof | |
| CN112494460B (en) | Tilmicosin powder and preparation method thereof | |
| CN112843011B (en) | Tilmicosin premix and preparation method thereof | |
| CN111569045A (en) | Florfenicol soluble powder medicine | |
| CN106362159A (en) | Molecular skeleton type tilmicosin sustained release preparation and preparation method thereof | |
| KR100552800B1 (en) | L-Carnitine Supplement for Ruminants, and Method for Increasing Contents of L-Carnitine in Body and Its Products by Feeding The Supplement |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |