CN101491497A - Toltrazuril suspension preparation capable of being effectively uniformly dispersed in water and preparation method thereof - Google Patents
Toltrazuril suspension preparation capable of being effectively uniformly dispersed in water and preparation method thereof Download PDFInfo
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- CN101491497A CN101491497A CNA2008101545791A CN200810154579A CN101491497A CN 101491497 A CN101491497 A CN 101491497A CN A2008101545791 A CNA2008101545791 A CN A2008101545791A CN 200810154579 A CN200810154579 A CN 200810154579A CN 101491497 A CN101491497 A CN 101491497A
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Abstract
The invention discloses a Toltrazuril suspending agent dispersible in water and a method for preparing the same. The Toltrazuril suspending agent comprises 1 to 15 percent of Toltrazuril, 0.01 to 2.0 percent of a surfactant, 0.01 to 2.0 percent of an emulsifier, 0.1 to 0.3 percent of a preservative, 0.2 to 2.0 percent of a flocculant, 0.1 to 2.0 percent of a suspending aid, 1 to 20 percent of a wetting agent and 40 to 88 percent of purified water.
Description
Technical field
The present invention relates to a kind of toltrazuril suspension preparation and preparation method thereof.
Background technology
Chicken coccidiosis is the parasitic disease of being produced by the caused serious harm aviculture of Eimeria (Eimeria).The Eimeria that parasitizes in the Intestinum Gallus domesticus road has 7 kinds, is respectively Eimeria tenella (E.tenella), heap type Eimeria (E.acervulina), murder by poisoning Eimeria (E.necatrix), Eimeria maxima (E.maxima), gentle Eimeria (E.mitis), Bu Shi Eimeria (E.brinetti) and precocious Eimeria (E.praecox).Various coccidiosiss are in the entozoic position of chicken digestive tract difference, Eimeria tenella parasitizes caecum, heap type Eimeria parasitizes duodenum, and Eimeria maxima and murder by poisoning Eimeria parasitize small intestinal, and the Bu Shi Eimeria parasitizes small intestinal hypomere and rectum.
Chicken coccidiosis is that a kind of whole world generally takes place the very serious parasitic disease of poultry husbandry harm.Its economic loss that causes is surprising.In the middle of many mass-sending diseases, the sickness rate of chicken coccidiosis is the highest, accounts for 17～20%.Chicken coccidiosis is widely distributed, we can say that just there is chicken coccidiosis in the place of chicken, at intensification chicken farm its sickness rate up to 50～70%; Mortality rate reaches 20～30%, more can reach 80% when serious.
Toltrazuril (Toltrazuril) is very extensive to the site of action of coccidiosis, and two no sexual cycles of coccidiosis are all had effect, as suppressing schizont, the wall organizator of the karyokinesis of microgametophyte and microgametophyte.Because this product is disturbed division of coccidiosis nucleus and mitochondrion, influence breathing and the metabolic function of polypide, endocytoplasmic reticulum is expanded, serious ghostization takes place, thereby has the worm of killing effect.
In home poultry raising, poultry-farm or specialist often adopt the mode of drinking-water administration to carry out fowl diseases prevention and treatment, because the drinking-water administration is easy, time saving and energy saving, can reduce or avoid the chicken stress simultaneously.Though toltrazuril has the effect of good wide spectrum anticoccidial, because there is the shortcoming that is insoluble in water in toltrazuril, the medicine of the relevant toltrazuril of clinical practice both at home and abroad has only a kind of dosage form of toltrazuril solution at present, the method of using toltrazuril, triton x-100 and Polyethylene Glycol to prepare anticoccidial solution has been described as CN200610038079.2, after being heated to Polyethylene Glycol between 100 degrees centigrade to 120 degrees centigrade, add toltrazuril, after stirring makes the toltrazuril dissolving, add triton x-100 again, obtain anticoccidial solution after stirring; Its shortcoming is to need in the preparation process to use as organic solvents such as Polyethylene Glycol to dissolve, and will be heated under the condition more than 120 ℃ and could dissolve, and will have following problem or deficiency like this:
1, cost of supplementary product height: consumption of organic solvent is very big, and the aqueous solution cost is very high relatively.
2, manufacturing expense height: manufacture process needs heating, cooling, and consumes energy is many, the manufacturing cost height.
3, medicine stability is poor, and general toltrazuril will add in the organic solvent under being higher than 120 ℃ temperature and dissolves, the less stable of toltrazuril under the condition of high temperature, and quality is difficult to controlled.
Summary of the invention
In order to overcome the above problems, the invention provides a kind of toltrazuril suspension preparation that can effectively be dispersed in the water, toltrazuril suspension is compared with toltrazuril solution and is had following advantage:
1, toltrazuril suspension safety of medicine, toxicity is low.Because the solvent of toltrazuril solution 100% is an organic solvent, a large amount of organic solvents can cause individual anaphylaxis etc., and the toltrazuril suspensoid really drops to the addition of organic solvent below 20%.
2, the toltrazuril suspension cost reduces, and compares with toltrazuril solution, because significantly reduced the consumption of organic solvent, and adopts water to make solvent, so cost reduces greatly.
3, toltrazuril suspension medicine stability height, if with toltrazuril be dissolved in make deccox solution in the solvent after, medicine is oxidation deterioration very easily, but when being to use suspending agent to be dispersed in the solid drugs microgranule in the solvent uniformly, medicine is just very stable.
4, the drug particle of toltrazuril suspension has adhesion to intravital mucous membrane tissue, has prolonged the medicine holdup time in vivo, has improved bioavailability of medicament.
5, toltrazuril suspension medicine drug loading height can increase to 15% with the content of principal agent.
6, toltrazuril suspension dispersion, good stability in water.
Toltrazuril suspension preparation of the present invention is made by the composition of following proportioning:
Toltrazuril 1%～15%
Surfactant 0.01%～2.0%
Emulsifying agent 0.01%～2.0%
Antiseptic 0.1%～0.3%
Flocculating agent 0.2%～2.0%
Suspending agent 0.1%～2.0%
Wetting agent 1%～20%
Purified water 40～88%
The percentage ratio of above composition is based on the gross weight meter of suspensoid.
Preparation method:
(1) gets 13-30% (W/W) purified water, add antiseptic 0.1%～0.3% (W/W) and flocculating agent 0.2%～2.0% (W/W), after the stirring and dissolving, get solution A;
(2) get 13-30% (W/W) purified water, expanded after adding suspending agent 0.1%～2.0% stirs, get solution B;
(3) solution B is poured in the solution A, after stirring, adding anion surfactant 0.01%～2.0% stirred 10 minutes, add emulsifying agent 0.01%～2.0%, wetting agent 1%～20%, suspending agent 0.1%～2.0%, toltrazuril 1%～15% more successively, behind the stirring and evenly mixing, add the residue purified water and make total amount, obtain solution C to 100g;
(4) solution C is homogenized by high pressure homogenizer;
(5) obtain stable toltrazuril suspension by 2-3 circulation after homogenizing.
The solid particle size scope of the middle toltrazuril of described toltrazuril suspension is 1-15000nm.
Above-mentioned surfactant comprises but is not limited to: a kind of or combination of sodium laurylsulfate, Diocty Sodium Sulfosuccinate, dodecyl sodium sulfate etc., the best is a Diocty Sodium Sulfosuccinate.
Above-mentioned emulsifying agent is selected from: dimethyl-silicon fat liquor, Tween 80.
Foregoing preservatives is selected from: a kind of or combination in sodium propionate, benzoic acid, methyl hydroxybenzoate, ethyl hydroxybenzoate, the propylparaben.
Above-mentioned flocculating agent is selected from: a kind of or combination in anhydrous citric acid, sodium citrate, tartrate, the phosphate.
Above-mentioned suspending agent is selected from: a kind of or combination in sodium alginate, agar, xanthan gum, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, aluminium-magnesium silicate, silicon Bentonite, the bentonite.
Above-mentioned wetting agent is selected from: ethanol, glycerol, 1, and a kind of or combination in the 2-propylene glycol, optimum selection is 1, and 2-propylene glycol, consumption are 1～20% (V/V), and optimum amount is 5～15% (V/V).
Purpose of the present invention also provides the purposes of a kind of toltrazuril suspension in the medicine of preparation treatment chicken coccidiosis.
The specific embodiment
Embodiment 1:
Component:
Toltrazuril 5.0g
Diocty Sodium Sulfosuccinate 0.25g
Dimethicone 0.05g
Sodium propionate 0.20g
Benzoic acid 0.20g
Aluminium-magnesium silicate 0.35g
Anhydrous citric acid 0.60g
Xanthan gum 0.30g
1,2-propylene glycol 10.0g
Purified water 83.0g
Collocation method:
(1) gets the 30g purified water, add sodium propionate 0.20g, benzoic acid 0.20g and anhydrous citric acid 0.6g, after the stirring and dissolving, get solution A.
(2) get the 30g purified water, expanded after adding xanthan gum 0.3g stirs, get solution B
(3) solution B is poured in the solution A, after stirring, added Diocty Sodium Sulfosuccinate 0.25g and stirred 10 minutes, add dimethicone 0.05g, 1 more successively, 2-propylene glycol 10g, aluminium-magnesium silicate 0.35g, toltrazuril 5g are behind the stirring and evenly mixing, add purified water 26.5g, obtain solution C.
(4) solution C is homogenized under the pressure of 100Mpa by high pressure homogenizer.
(5) by obtaining the toltrazuril suspension of solid particle size between 5-500nm behind 2 circulation homogenizing.
Embodiment 2:
Component:
Toltrazuril 2.5g
Dodecyl sodium sulfate 0.18g
Tween 80 0.50g
Methyl hydroxybenzoate 0.21g
Ethyl hydroxybenzoate 0.21g
Aluminium-magnesium silicate 0.35g
Sodium citrate 0.50g
Sodium carboxymethyl cellulose 1.13g
1,2-propylene glycol 8.6g
Purified water 86.5g
Collocation method:
(1) gets the 30g purified water, add sodium propionate 0.21g, benzoic acid 0.21g and sodium citrate 0.5g, after the stirring and dissolving, get solution A.
(2) get the 30g purified water, expanded after adding sodium carboxymethyl cellulose 0.5g stirs, get solution B
(3) solution B is poured in the solution A, after stirring, added dodecyl sodium sulfate 0.18g and stirred 10 minutes, add Tween 80 0.5g, 1 more successively, 2-propylene glycol 8.6g, aluminium-magnesium silicate 0.35g, toltrazuril 2.5g are behind the stirring and evenly mixing, add purified water 26.5g, obtain solution C.
(4) solution C is homogenized under the pressure of 60Mpa by high pressure homogenizer.
(5) by obtaining the toltrazuril suspension of solid particle size between 100-1000nm behind 2 circulation homogenizing.
Embodiment 3:
Component:
Toltrazuril 15.0g
Diocty Sodium Sulfosuccinate 0.53g
Dimethicone 0.07g
Sodium propionate 0.20g
Benzoic acid 0.20g
Aluminium-magnesium silicate 0.38g
Anhydrous citric acid 0.90g
Xanthan gum 0.48g
1,2-propylene glycol 12.1g
Glycerol 4.2g
Purified water 65.94g
Collocation method:
(1) gets the 20g purified water, add sodium propionate 0.20g, benzoic acid 0.20g and anhydrous citric acid 0.9g, after the stirring and dissolving, get solution A.
(2) get the 30g purified water, expanded after adding xanthan gum 0.48g stirs, get solution B
(3) solution B is poured in the solution A, after stirring, added Diocty Sodium Sulfosuccinate 0.53g and stirred 10 minutes, add dimethicone 0.07g, 1 more successively, 2-propylene glycol 12.1g, aluminium-magnesium silicate 0.38g, toltrazuril 15g are behind the stirring and evenly mixing, add purified water 15.9g, obtain solution C.
(4) solution C is homogenized under the pressure of 100Mpa by high pressure homogenizer.
(5) by obtaining the toltrazuril suspension of solid particle size between 5-500nm behind 2 circulation homogenizing.
Embodiment 4:
The stability test result:
1. accelerated tests is in order to measure this stability of formulation, requirement according to " veterinary drug stability test technical specification ", accelerated test under the ad hoc fixed following condition, product to embodiment 1, embodiment 2, embodiment 3 is tested, experimental condition: it is that 40 degrees centigrade, relative humidity are 75% calorstat that three kinds of Toltrazuril suspension samples of embodiment 1, embodiment 2, embodiment 3 are put into temperature, the sampling respectively in the 1st, 2,3,6 month, and observe character respectively and measure content, experimental result is as follows:
The Toltrazuril suspension of table 1 embodiment 1 quickens the stability test result
| Inspection item | Character | The settling volume ratio | Content |
| Before the experiment | The off-white color suspension | 0.94 | 5.11％ |
| One month | The off-white color suspension | 0.92 | 5.15％ |
| Two months | The off-white color suspension | 0.93 | 5.13％ |
| Three months | The off-white color suspension | 0.92 | 5.02％ |
| Six months | The off-white color suspension | 0.92 | 5.03％ |
The Toltrazuril suspension of table 2 embodiment 2 quickens the stability test result
| Inspection item | Character | The settling volume ratio | Content |
| Before the experiment | The off-white color suspension | 0.98 | 2.55％ |
| One month | The off-white color suspension | 0.98 | 2.55％ |
| Two months | The off-white color suspension | 0.97 | 2.53％ |
| Three months | The off-white color suspension | 0.98 | 2.52％ |
| Six months | The off-white color suspension | 0.98 | 2.50％ |
The Toltrazuril suspension of table 3 embodiment 3 quickens the stability test result
| Inspection item | Character | The settling volume ratio | Content |
| Before the experiment | The off-white color suspension | 0.92 | 15.5％ |
| One month | The off-white color suspension | 0.93 | 15.1％ |
| Two months | The off-white color suspension | 0.93 | 15.1％ |
| Three months | The off-white color suspension | 0.93 | 15.0％ |
| Six months | The off-white color suspension | 0.93 | 15.0％ |
From assay, in the phase, character does not all change the toltrazuril suspension of embodiment 1, embodiment 2, embodiment 3 at accelerated stability test, settling ratio illustrates that all greater than 0.9 dispersibility is fine, and content does not have significant change, every index all meets the requirements, and this product good stability is described.
2. the acceleration by light experiment is placed on the toltrazuril suspension (2.5%) of embodiment 2 and commercially available toltrazuril solution (2.5%) in the adjustable lighting box, preserves under the condition of illumination 2800Lux.In sampling in 5 days, 10 days, experimental result was as follows:
Table 4 light stability result of the test
From assay, toltrazuril solution solution colour under illumination deepens, illumination 10 days, and content reduces by 8.47%, and toltrazuril suspension of the present invention character and content under illumination all do not have significant change, show that the Toltrazuril suspension is stable than toltrazuril solution.
Claims (6)
1, a kind of toltrazuril suspension that is scattered in water is characterized in that described suspension is to be made by the composition of following proportioning:
Toltrazuril 1%～15%
Surfactant 0.01%～2.0%
Emulsifying agent 0.01%～2.0%
Antiseptic 0.1%～0.3%
Flocculating agent 0.2%～2.0%
Suspending agent 0.1%～2.0%
Wetting agent 1%～20%
Purified water 40～88%
The percentage ratio of above composition is based on the gross weight meter of suspensoid.
2,, it is characterized in that surfactant comprises but is not limited to according to the toltrazuril suspension of claim 1: a kind of or combination of sodium laurylsulfate, Diocty Sodium Sulfosuccinate, dodecyl sodium sulfate etc., the best is a Diocty Sodium Sulfosuccinate;
Emulsifying agent is selected from: dimethyl-silicon fat liquor, Tween 80 antiseptic 0.1%～0.3%: a kind of or combination in sodium propionate, benzoic acid, methyl hydroxybenzoate, ethyl hydroxybenzoate, the propylparaben;
Flocculating agent is selected from: a kind of or combination in anhydrous citric acid, sodium citrate, tartrate, the phosphate;
Suspending agent is selected from: a kind of or combination in sodium alginate, agar, xanthan gum, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl cellulose, aluminium-magnesium silicate, silicon Bentonite, the bentonite;
Wetting agent is selected from: ethanol, glycerol, 1, a kind of or combination in the 2-propylene glycol.
3, according to the toltrazuril suspension of claim 1 or 2, it is characterized in that wetting agent is selected from 1,2-propylene glycol, consumption are 1～20% (V/V), optimum amount is 5～15% (V/V).
4, according to each toltrazuril suspension of claim 1-3, it is characterized in that the solid particle size scope of the toltrazuril in the toltrazuril suspension is 1-15000nm.
5, the method for the toltrazuril suspension of the be scattered in water of preparation claim 1 is characterized in that comprising:
(1) gets 13-30% (W/W) purified water, add antiseptic and flocculating agent, after the stirring and dissolving, get solution A;
(2) get 13-30% (W/W) purified water, add suspending agent, expanded after stirring, get solution B;
(3) solution B is poured in the solution A, after stirring, added anion surfactant and stirred 10 minutes, add emulsifying agent, wetting agent, suspending agent, toltrazuril more successively, behind the stirring and evenly mixing, add the residue purified water and make total amount, obtain solution C to 100g;
(4) solution C is homogenized by high pressure homogenizer;
(5) obtain stable toltrazuril suspension by 2-3 circulation after homogenizing.
6, according to each the purposes of toltrazuril suspension in the medicine of preparation treatment chicken coccidiosis of claim 1-4.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008101545791A CN101491497A (en) | 2008-12-26 | 2008-12-26 | Toltrazuril suspension preparation capable of being effectively uniformly dispersed in water and preparation method thereof |
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| CNA2008101545791A CN101491497A (en) | 2008-12-26 | 2008-12-26 | Toltrazuril suspension preparation capable of being effectively uniformly dispersed in water and preparation method thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101773474A (en) * | 2010-02-26 | 2010-07-14 | 湖北龙翔药业有限公司 | Preparation method of toltrazuril soluble powder |
| CN102973502A (en) * | 2012-11-08 | 2013-03-20 | 河南牧翔动物药业有限公司 | Toltrazuril nano-suspension and preparation method thereof |
| CN103070164A (en) * | 2013-02-26 | 2013-05-01 | 江苏省苏科农化有限责任公司 | Novel method for preparing pesticide suspending agents |
| CN103694185A (en) * | 2013-12-18 | 2014-04-02 | 湖北龙翔药业有限公司 | Toltrazuril alkali metal salt as well as preparation method and application thereof |
| CN108295038A (en) * | 2018-03-12 | 2018-07-20 | 江苏凌云药业股份有限公司 | A kind of enteric-coated composition for animals 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 |
| CN113577082A (en) * | 2021-08-23 | 2021-11-02 | 瑞普（天津）生物药业有限公司 | Veterinary compound toltrazuril preparation and preparation method thereof |
| 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 |
-
2008
- 2008-12-26 CN CNA2008101545791A patent/CN101491497A/en active Pending
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101773474A (en) * | 2010-02-26 | 2010-07-14 | 湖北龙翔药业有限公司 | Preparation method of toltrazuril soluble powder |
| CN102973502A (en) * | 2012-11-08 | 2013-03-20 | 河南牧翔动物药业有限公司 | Toltrazuril nano-suspension and preparation method thereof |
| CN103070164A (en) * | 2013-02-26 | 2013-05-01 | 江苏省苏科农化有限责任公司 | Novel method for preparing pesticide suspending agents |
| CN103694185A (en) * | 2013-12-18 | 2014-04-02 | 湖北龙翔药业有限公司 | Toltrazuril alkali metal salt as well as preparation method and application thereof |
| CN108295038A (en) * | 2018-03-12 | 2018-07-20 | 江苏凌云药业股份有限公司 | A kind of enteric-coated composition for animals and preparation method thereof |
| CN108295038B (en) * | 2018-03-12 | 2020-08-28 | 江苏凌云药业股份有限公司 | Veterinary enteric composition 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 |
| CN113577082A (en) * | 2021-08-23 | 2021-11-02 | 瑞普（天津）生物药业有限公司 | Veterinary compound toltrazuril preparation and preparation method thereof |
| 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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