CN105534894A - Thixotropic anti-coccidia suspension and preparation method thereof - Google Patents
Thixotropic anti-coccidia suspension and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
Abstract
The invention discloses a thixotropic anti-coccidia suspension which is prepared from the following components according to mass volume: 0.5-20.0g/100ml of anti-coccidia drug, 0.1-5.0g/100ml of thixotropic suspending aid, 0-5.0g/100ml of suspending aid, 0.1-20.0g/100ml of wetting agent, 0.1-5.0g/100ml of surfactant, 0.1-6.0g/100ml of flocculant, 0.01-0.5g/100ml of preservative, 0.1-10.0g/100ml of stabilizer and the balance of water. The thixotropic anti-coccidia suspension disclosed by the invention has the advantages of increased drug stability, prolonged in-vivo residence time, improved bioavailability, simple preparation technology, easiness in storage and the like.
Description
Technical field
The present invention relates to a kind of thixotropic coccidium-resistant suspension and preparation method thereof, described thixotropic coccidium-resistant suspension is oral suspensions, belongs to treating animal coccidiosis medicine field.
Background technology
Coccidiosis is a kind of parasitic disease, and in the poultry of high-density rearing on a large scale, sickness rate is higher.Coccidiosis is caused by parasite Eimeria (Amy ear).The life cycle of Eimeria is approximately 4-7 days.Parasite breeds at double at little enteral and causes tissue injury, reduces the absorbance of nutrient in feed intake and feedstuff, dehydration and blood loss, causes livestock meat egg to be produced and occurs heavy losses.Animal body can produce immunity rapidly after contact cause of disease, and produces the protectiveness infected again, and therefore coccidiosis only breaks out in growing animal mostly.But, there is no cross immunity between each worm kind of Eimeria, be easy to break out the coccidiosis caused by different worm kind.Modern scale and enclosed aquaculture model more make this life cycle short, and make disease be difficult to control, conventional chemoprophylaxis, sterilization and vaccine epidemic prevention effect are very weak.
Toltrazuril, chemistry 1-methyl-3-[3-methyl-4-(4-trifluoromethyl sulfo-) phenoxy group] phenyl-1,3,5-triazines-2,4,6-triketone by name, referred to as methyl triazon, has another name called toltrazuril, Baycox, belongs to Triazinone derivant.Molecular formula is C
18h
14f
3n
3o
4s, molecular weight is 425.4, Toltrazuril is white crystalline powder, odorless, fusing point 194 DEG C, water insoluble, be slightly soluble in ethanol, dissolve in Polyethylene Glycol, the organic solvent such as propylene glycol, ethyl acetate, DMF (DMF), dimethyl sulfoxide (DMSO), oxolane (THF), diethyl carbonate, toluene.Toltrazuril is triazines wide spectrum anticoccidial drug, and effectively can kill the multiple protozoon comprising coccidiosis, toxicity is low, not easily produces drug resistance, all has effect, be mainly used in the control of coccidiosis of livestock and poultry to each stage that coccidiosis grows.Its to chicken heap-type, Podbielniak, huge, gentle, poison, Eimeria Tenella and turkey gland eimeria tenella, el pato worm all have good inhibitory or killing effect, do not affect bird and grow and generation to immunity to coccidiosis power.Also good curative effect is had to the liver coccidiosis of rabbit and the sorosphere insect infection of intestinal coccidiosis and piglet.
Diclazuril belongs to triazine benzene acetonitrile platform thing, chemistry by name 2, the chloro-2-of 6-bis-(4-chlorobenzene)-4-(4,5-dihydro-3,5-dioxo-1,2,4-triazine-2 (3H)-Ji) benzene acetonitrile, for novel, efficient (as long as feedstuff per ton adds this compound of 1g), low toxicity (excessive 50 times do not find intoxicating phenomenon) anticoccidial drug, be widely used in chicken coccidiosis.There is prophylactic treatment effect to multiple coccidiosis in addition, also can be used for preventing from avoiding duck, Carnis Coturnicis japonicae, turkey, goose and rabbit to obtain coccidiosis.Diclazuril is a kind of nonionic portable type coccidiostat of brand-new synthetic, this product to the anticoccidial index of six of chicken kinds of main eimeria tenellas all more than 180, belong to efficient coccidiostat, also there is low toxicity, wide spectrum, consumption is little, safety range is wide, without withdrawal time, have no side effect, without cross resistance, not by the feature such as impact of feed granulating process.This product can make an addition in feedstuff for a long time, without the need to drug withdrawal before butchering.
Deccox is off-white color or micro-yellow crystalline powder, chemical name is DECCOX, deccox (decoquinate) is a kind of very effective quinolones poultry anticoccidial drug, it is mainly through the stage suppresses sporocyst in the early stage, and mid-term stage is killed early stage schizont and plays a role.
There is very large weakness in the anticoccidial drugs such as Toltrazuril, diclazuril and deccox, is exactly that it belongs to poorly water soluble drugs.At present, the dosage form of Toltrazuril medicine mainly contains pre-mixing agent, powder, solution (CN1839845A), microemulsion (CN101336901A), nano suspension (CN101947201A) etc.; The dosage form of diclazuril medicine has pre-mixing agent (CN1460485A), solution (CN1875983A, CN1839879A, CN101642460A, CN101972262A, CN102327268A etc.), soluble powder (CN101669911A), microemulsion (CN101152183A), suspensoid (CN101904858A, CN102000100A); The dosage form of deccox medicine has pre-mixing agent, solution (CN101129371A, CN102106814A), soluble powder (CN101606908A, CN101590055A, CN101933930A), suspensoid (CN101496786A, CN102008435A), listing product with powder and solution in the majority, consider the convenience of fowl poultry kind colony dosing techniques, in veterinary drug clinical practice, often adopt the administering mode such as mixed feeding, drinking-water, injection.Because the anticoccidial drug quantities such as Toltrazuril, diclazuril and deccox are low, not easily mix with during food premix, and the poultry in morbid state search for food less, thus curative effect is reduced or takes in too much and produce untoward reaction.Because drug solution is many containing organic solvent during solution drinking water administration, the administration of mixed drink easily produces crystallization or precipitation, causes animal can not fully absorb enough medicines.And microemulsion and nano suspension preparation cost is higher, clinical expansion has some limitations.
Suspensoid refers to that insoluble solid medicine is scattered in the heterogeneous liquid preparation formed in liquid medium with graininess.Suspendible technology is the better method solving insoluble medicine dissolving and the problem of absorption, but the easy sedimentation of general suspensoid, after sedimentation, redispersibility is poor, is the key issue that suspension stability exists, and easily cause divided dose inaccurate, and affect the treatment or produce untoward reaction.
Summary of the invention
The object of the invention is on the basis of existing technology, a kind of thixotropic coccidium-resistant suspension be provided, this suspension cost is low, stability is high, evident in efficacy, eco-friendly dosage form.
Another object of the present invention is to provide a kind of preparation method of above-mentioned thixotropic coccidium-resistant suspension.
Object of the present invention can be reached by following measures:
A kind of thixotropic coccidium-resistant suspension, it is oral suspensions, and it is made up of the component of following quality volume content (g/100mL):
Wherein, described anticoccidial drug can select the multiple medical compounds with Anti-human globulin test of the prior art, preferably adopts one or more in Toltrazuril, diclazuril and deccox in the application.
Solids size controlling in the present invention is the granule of 0.1 ~ 20 μm, and preferable particle size is distributed as 1 ~ 15 μm.
Thixotropic suspensoid stability compared with common suspensoid is higher.Thixotropic suspensoid has excellent thixotropy: during static placement, and suspension keeps high viscosity, medicine sedimentation slowly or sedimentation hardly, ensure that the suspension of medicine and content even; During use, jog can mix, and suspension presents the good fluidity of solution, is convenient to topple over and divided dose, easy to use.We are when developing the suspensoid of Toltrazuril, diclazuril and deccox, suitable thixotropic suspending agent is adopted to provide thixotropy for coccidium-resistant suspension, and add the adjuvant of suitable kind and amount, obtained a kind of stable thixotropic coccidium-resistant suspension through rational preparation technology.
Thixotropic suspending agent in the present invention includes but not limited to one or more in aluminium-magnesium silicate, aluminium stearate, xanthan gum, microcrystalline Cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, methylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose; One or more in preferably microcrystalline cellulose, sodium carboxymethyl cellulose, xanthan gum; The preferred quality volume content of thixotropic suspending agent is 0.5 ~ 5.0g/100ml.
Suspending agent in the present invention includes but not limited to one or more in glycerol, agar, tragakanta, arabic gum, sodium alginate, polyvinylpyrrolidone, carbomer, silicon Bentonite, bentonite, is mainly the viscosity that thixotropic coccidium-resistant suspension provides suitable; The quality volume content of suspending agent is 0 ~ 5.0g/100ml, namely can not comprise suspending agent in this thixotropic coccidium-resistant suspension, and in a kind of preferred version, the quality volume content of suspending agent is 0.1 ~ 5.0%.
Wetting agent in the present invention includes but not limited to one or more in ethanol, 1,2-PD, glycerol, triethanolamine, PEG200 ~ 600, and the medicine be mainly in thixotropic coccidium-resistant suspension provides suitable dispersibility; The preferred quality volume content of wetting agent is 0.5 ~ 20.0g/100ml.
Surfactant in the present invention includes but not limited to one or more in simethicone emulsion, polysorbas20 ~ 80, span 20 ~ 80, sodium laurylsulfate, Diocty Sodium Sulfosuccinate, dodecyl sodium sulfate, poloxamer, carbomer, polyoxyethylene nonylphenol ether, helps the medicaments uniformity dispersion in thixotropic coccidium-resistant suspension; The preferred quality volume content of surfactant is 0.1 ~ 5.0g/100ml.
Flocculating agent in the present invention includes but not limited to one or more in citric acid, citrate, tartrate, biatrate, phosphate, chloride; The preferred quality volume content of flocculating agent is 0.1 ~ 6.0g/100ml.
Antiseptic in the present invention includes but not limited to one or more in methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, butoben, dehydro sodium acetate, sodium propionate, benzoic acid, sodium benzoate, sorbic acid, sodium sorbate, potassium sorbate, and the quality volume content of antiseptic is 0.01 ~ 0.5g/100ml.
Stabilizing agent in the present invention include but not limited in polyvinylpolypyrrolidone, aerosil one or both, the content of stabilizing agent is 0.1 ~ 10.0g/100ml; Described water is purified water.
The thixotroping suspendible that flocculating agent and stabilizing agent are thixotropic coccidium-resistant suspension provides stability.
Present invention also offers a kind of preparation method of above-mentioned thixotropic coccidium-resistant suspension, it comprises the steps:
(1) get part water, add thixotropic suspending agent and suspending agent stirring, expanded, obtain homodisperse solution A;
(2) add wetting agent, surfactant and anticoccidial drug successively to the solution A in stirring, dispersed with stirring is even obtains solution B;
(3) separately get part water, add antiseptic and flocculating agent, after stirring and dissolving, obtain solution C;
(4) solution C is poured in solution B, after stirring, add stabilizing agent, after stirring and evenly mixing, add the water of surplus, obtain solution D;
(5) solution D undertaken disperseing and homogenizing by homogenizer, the pressure that adopts of homogenizing is at 100 ~ 240MPa, and temperature controls at 0 ~ 40 DEG C, and being homogenized by 3 ~ 8 circulations to be required to particle diameter regulation and get final product.
Thixotropic anticoccidial suspension of the present invention has following advantage compared with above-mentioned preparation:
1. thixotropic suspensoid stability compared with common suspensoid is high.Suspension of the present invention has excellent thixotropy: during static placement, and suspension keeps high viscosity, medicine sedimentation slowly or sedimentation hardly, ensure that the suspension of medicine and content even; During use, jog can mix, and suspension presents the good fluidity of solution, is convenient to topple over and divided dose, easy to use, has good stability.
2. thixotropic coccidium-resistant suspension of the present invention is fill carrier with water, nontoxic safer.As far as possible without organic solvent in suspension, greatly reduce the untoward reaction because organic solvent causes
3. the drug particle particle diameter of thixotropic coccidium-resistant suspension of the present invention is less, and particle size distribution interval is narrow, is easy in mucous membrane of animal tissue deposition, and thus medicine is at the increased retention of morbid state individuality, is conducive to the raising of drug bioavailability.
Thixotropic coccidium-resistant suspension of the present invention forms stable suspension, and it has medicine stability increases, increased retention in body, and bioavailability improves, and preparation technology is simple, is easy to the advantages such as preservation.
Detailed description of the invention
Following instance for illustration of the present invention, but is not used for limiting the scope of the invention.
Solids size controlling in following instance is the granule of 0.1-20 μm, and preferable particle size is distributed as 1-15 μm.
Embodiment 1:0.5% diclazuril thixotropic anticoccidial suspension
Formula:
The preparation technology of this thixotropic coccidium-resistant suspension comprises the steps:
(1) get partial purification water, add thixotropic suspending agent, suspending agent stirs, expanded, obtain homodisperse solution A;
(2) add wetting agent successively, surfactant, anticoccidial drug to the solution A in stirring, dispersed with stirring is even obtains solution B;
(3) separately get partial purification water, add antiseptic, flocculating agent, after stirring and dissolving, obtain solution C;
(4) pour in solution B by solution C, after stirring, add stabilizing agent, after stirring and evenly mixing, the purified water adding surplus is settled to full dose, obtains solution D.
(5) solution D undertaken disperseing and homogenizing by high pressure homogenizer, the pressure adopted when homogenizing is at 100 ~ 200MPa, and temperature controls at 0 ~ 50 DEG C.
(6) homogenized to particle diameter by 3 ~ 8 circulations and to conform with the regulations requirement, obtain stable thixotropic coccidium-resistant suspension.
The preparation technology of following examples carries out with reference to embodiment 1.
Embodiment 2:5% deccox thixotropic anticoccidial suspension
Formula:
The pressure adopted when homogenizing is at 100MPa, and temperature controls at 0 DEG C
Embodiment 3:10% diclazuril thixotropic anticoccidial suspension
Formula:
The pressure adopted when homogenizing is at 200MPa, and temperature controls at 10 DEG C
Embodiment 4:20% diclazuril thixotropic anticoccidial suspension
Formula:
The pressure adopted when homogenizing is at 240MPa, and temperature controls at 20 DEG C
Embodiment 5:1.0% diclazuril thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 150MPa, and temperature controls at 30 DEG C
Embodiment 6:5% Toltrazuril thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at 40 DEG C
Embodiment 7:10% Toltrazuril thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at 50 DEG C
Embodiment 8:5% Toltrazuril+5% deccox thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at room temperature (18 ~ 26 DEG C)
Embodiment 9:20% Toltrazuril thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at 20 DEG C.
Embodiment 10:5% diclazuril+2.5% deccox thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at 30 DEG C.
Embodiment 11:10% Toltrazuril+5% oxygen in last of the ten Heavenly stems quinoline thixotropic ester suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at 40 DEG C.
Embodiment 12:5% Toltrazuril+2.5% deccox thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at 25 DEG C.
Embodiment 13:1.0% Toltrazuril thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at 25 DEG C.
Embodiment 14:5.0% Toltrazuril thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 180MPa, and temperature controls at 25 DEG C.
Embodiment 15:10.0% Toltrazuril thixotropic suspension
Formula:
The pressure adopted when homogenizing is at 200MPa, and temperature controls at 25 DEG C.
Embodiment 16: the suspension quality evaluation of thixotropic anticoccidial and study on the stability
The present embodiment carries out quality evaluation and stability test to the thixotropic suspension prepared in embodiment of the present invention 5-15.Method of testing is as described below.
One, quality evaluation method of testing
Under [sedimentation volume ratio] takes suspensoid item orally according to Chinese veterinary pharmacopoeia 2010 editions annex, requirement measures.Suspensoid for oral administration is according to following method inspection, and sedimentation volume ratio should be not less than 0.97.
Unless otherwise specified, apparatus plug graduated cylinder measures test sample 50ml to inspection technique, close plug, and firmly jolting 1 minute, writes down the beginning height H of suspended matter
0, leave standstill 3 hours, write down the final height H of suspended matter, be calculated as follows: sedimentation volume ratio=H/H
0
[particle size determination] adopts laser particle instrument to measure the particle size distribution of suspension particle.
Measurement result:
After the anticoccidial drug suspension samples such as [sedimentation volume ratio] Toltrazuril of the present invention, diclazuril and deccox leave standstill 3h, sedimentation face does not change.
The particle size distribution of [particle size determination] formula 5-15 is narrower, and particle diameter is all in micron level.
The quality evaluation test result of table 1 thixotropic suspensoid
Two, stability test
(1) accelerated test
For investigating the stability of invention formulation, according to " veterinary drug stability test technical specification ", spy is set as follows the accelerated test under condition, investigates the sample of embodiment 5-15.Experimental condition: the climatic chamber 8 of embodiment 5-15 kinds of suspension samples being put into temperature 30 ± 2 DEG C, relative humidity 65 ± 5%, in the 1st, 2,3, within 6 months, sample respectively, and observe the outward appearance of sample, redispersibility, sedimentation volume ratio measure medicament contg etc. respectively, experimental result is as follows:
1.0% diclazuril thixotropic suspension acceleration for stabilization result of the test of table 2 embodiment 5
5.0% Toltrazuril thixotropic suspension acceleration for stabilization result of the test of table 3 embodiment 6
10.0% Toltrazuril thixotropic suspension acceleration for stabilization result of the test of table 4 embodiment 7
5.0% Toltrazuril+5.0% deccox thixotropic suspension acceleration for stabilization result of the test of table 5 embodiment 8
20.0% Toltrazuril thixotropic suspension acceleration for stabilization result of the test of table 6 embodiment 9
2.5% diclazuril+2.5% deccox thixotropic suspension acceleration for stabilization result of the test of table 7 embodiment 10
10% Toltrazuril+5% deccox thixotroping suspension acceleration for stabilization result of the test of table 8 embodiment 11
5% Toltrazuril+2.5% deccox thixotroping suspension acceleration for stabilization result of the test of table 9 embodiment 12
1.0% Toltrazuril thixotropic suspension acceleration for stabilization result of the test of table 10 embodiment 13
5.0% Toltrazuril thixotropic suspension acceleration for stabilization result of the test of table 11 embodiment 14
10.0% Toltrazuril thixotropic suspension acceleration for stabilization result of the test of table 12 embodiment 15
From result of the test, the suspension of embodiment 5-15 is within the accelerated stability test phase, and character does not all change, and settling volume ratio is all greater than 0.97, and content does not have significant change, and indices all meets the requirements, and illustrates that suspension of the present invention has good stability.
Claims (10)
1. a thixotropic coccidium-resistant suspension, is characterized in that it is made up of the component of following quality volume content:
Wherein, described anticoccidial drug is selected from one or more in Toltrazuril, diclazuril and deccox.
2. thixotropic coccidium-resistant suspension according to claim 1, it is characterized in that described anticoccidial drug controls the granule that particle diameter is 0.1 ~ 20 μm, preferable particle size is the granule of 1 ~ 15 μm.
3. thixotropic coccidium-resistant suspension according to claim 1, is characterized in that one or more that described thixotropic suspending agent is selected from aluminium-magnesium silicate, aluminium stearate, xanthan gum, microcrystalline Cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, methylcellulose, hydroxyethyl-cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose; One or more in preferably microcrystalline cellulose, sodium carboxymethyl cellulose, xanthan gum; The quality volume content of thixotropic suspending agent is 0.1 ~ 5.0g/100ml.
4. thixotropic coccidium-resistant suspension according to claim 1, is characterized in that one or more that described suspending agent is selected from glycerol, agar, tragakanta, arabic gum, sodium alginate, polyvinylpyrrolidone, carbomer, silicon Bentonite, bentonite; The quality volume content of suspending agent is 0 ~ 5.0g/100ml.
5. thixotropic coccidium-resistant suspension according to claim 1, is characterized in that one or more that described wetting agent is selected from ethanol, 1,2-PD, glycerol, triethanolamine, PEG200 ~ 600; The quality volume content of wetting agent is 0.5 ~ 20.0g/100ml.
6. thixotropic coccidium-resistant suspension according to claim 1, is characterized in that one or more that described surfactant is selected from simethicone emulsion, polysorbas20 ~ 80, span 20 ~ 80, sodium laurylsulfate, Diocty Sodium Sulfosuccinate, dodecyl sodium sulfate, poloxamer, carbomer, polyoxyethylene nonylphenol ether; The quality volume content of surfactant is 0.1 ~ 5.0g/100ml.
7. thixotropic coccidium-resistant suspension according to claim 1, is characterized in that one or more that described flocculating agent is selected from citric acid, citrate, tartrate, biatrate, phosphate, chloride; The quality volume content of flocculating agent is 0.1 ~ 6.0g/100ml.
8. thixotropic coccidium-resistant suspension according to claim 1, it is characterized in that one or more that described antiseptic is selected from methyl hydroxybenzoate, ethyl hydroxybenzoate, propylparaben, butoben, dehydro sodium acetate, sodium propionate, benzoic acid, sodium benzoate, sorbic acid, sodium sorbate, potassium sorbate, the quality volume content of antiseptic is 0.01 ~ 0.5g/100ml.
9. thixotropic coccidium-resistant suspension according to claim 1, it is characterized in that described stabilizing agent is selected from polyvinylpolypyrrolidone, aerosil one or both, the content of stabilizing agent is 0.1 ~ 10.0g/100ml; Described water is purified water.
10. the preparation method of the thixotropic coccidium-resistant suspension in claim 1-9 described in any one, is characterized in that it comprises the steps:
(1) get part water, add thixotropic suspending agent and suspending agent stirring, expanded, obtain homodisperse solution A;
(2) add wetting agent, surfactant and anticoccidial drug successively to the solution A in stirring, dispersed with stirring is even obtains solution B;
(3) separately get part water, add antiseptic and flocculating agent, after stirring and dissolving, obtain solution C;
(4) solution C is poured in solution B, after stirring, add stabilizing agent, after stirring and evenly mixing, add the water of surplus, obtain solution D;
(5) solution D undertaken disperseing and homogenizing by homogenizer, the pressure adopted when homogenizing is at 100 ~ 240MPa, and temperature controls at 0 ~ 50 DEG C, and being homogenized by 3 ~ 8 circulations to be required to particle diameter regulation and get final product.
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| CN106265503A (en) * | 2016-08-19 | 2017-01-04 | 浙江汇能生物股份有限公司 | A kind of high stability diclazuril suspension and preparation method thereof |
| CN108186561A (en) * | 2018-03-12 | 2018-06-22 | 石家庄市金元康牧药业有限公司 | A kind of solution of diclazuril and preparation method thereof |
| CN108403630A (en) * | 2018-05-31 | 2018-08-17 | 佛山市南海东方澳龙制药有限公司 | Suspension and preparation method thereof |
| CN108904514A (en) * | 2018-07-26 | 2018-11-30 | 日照市牧邦畜牧科技有限公司 | A kind of long stable effect compound solution of diclazuril and its preparation process |
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| CN108403630A (en) * | 2018-05-31 | 2018-08-17 | 佛山市南海东方澳龙制药有限公司 | Suspension and preparation method thereof |
| CN108904514A (en) * | 2018-07-26 | 2018-11-30 | 日照市牧邦畜牧科技有限公司 | A kind of long stable effect compound solution of diclazuril and its preparation process |
| CN114288241A (en) * | 2021-12-14 | 2022-04-08 | 河南中盛动物药业有限公司 | Toltrazuril suspension and preparation method thereof |
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