CN1839879A - Coccidian resistant solution containing diclazuril ,maduramicin ammonium and its preparation method - Google Patents
Coccidian resistant solution containing diclazuril ,maduramicin ammonium and its preparation method Download PDFInfo
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- CN1839879A CN1839879A CN 200610038078 CN200610038078A CN1839879A CN 1839879 A CN1839879 A CN 1839879A CN 200610038078 CN200610038078 CN 200610038078 CN 200610038078 A CN200610038078 A CN 200610038078A CN 1839879 A CN1839879 A CN 1839879A
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- diclazuril
- anticoccidial
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- ammonium
- maduramycin ammonium
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Abstract
The invention discloses a coccidian-resisting solution containing Diclazuril and Maduramicin ammonium and its preparing process, wherein the solution is compound water-soluble preparation comprising Diclazuril, Maduramicin ammonium, Triton-X100 and polyethylene glycol.
Description
Technical field
The present invention relates to veterinary drug of a kind of anticoccidial and preparation method thereof, particularly composite anticoccidial solution of diclazuril and Maduramycin Ammonium and preparation method thereof.
Background technology
In the prior art, chicken coccidiosis is the chicken parasitic disease that is caused by Eimeria, and the chickling sickness rate of 5-30 age in days is up to more than 80%, and mortality rate is up to 30%.The incidence rate of coccidiosis is the highest in various fowl disease, accounts for 15%-20%, is at present to the maximum a kind of parasitic disease of poultry husbandry harm.According to Bhogai (1992), whole world every year because of chicken coccidiosis cause with a toll of 2,000,000,000 dollars.Because the raising condition in scale intensification chicken farm is particularly suitable for the growth of coccidian oocyst spore; and egg capsule is only to thermo-responsive; disinfectant commonly used there is very strong resistance; so be difficult to prevent the generation of chicken coccidiosis with the administration of health means; the means of control chicken coccidiosis are still based on chemoprophylaxis at present; annual coccidiostat annual turnover accounts for about 10% of veterinary drug total sales volume at 2,000,000,000 yuan.Coccidiostat is a most active part in veterinary drug production and the development.
One of parasitic immune characteristics are " premunitions ", and the trophophase that coccidiosis is invaded behind the body is 2 days asexual propagation and sexual propagation in 5 days.An invasion egg capsule can be bred into 250,000 egg capsules in these 7 days, the harm body.Some medicine anticoccidial effect is fine, but in early days coccidiosis is all killed, and is unfavorable for that so on the contrary body produces immunity and resists extraneous parasitic intrusion.Medicine that has such as Maduramicin, its anticoccidial effect is certain, but toxicity is bigger, and effective dose and toxic dose are approaching, and people dare not be in clinical use.Through long term studies with to the screening of tens of kinds of coccidiostats, the anticoccidial effect of diclazuril and Maduramicin is able to really.
Maduramicin, English name Maduramicin ammonium, molecular formula B
1aC
47H
79O
17(NH
4), molecular weight 934.17, structural formula:
Be a kind of effective coccidiosis agent for killing, kill the intravital parasite of host, rather than the coccidiosis inhibitor.Its active phase is initial 1 to 3 day at the coccidiosis life cycle.Can kill zygoblast and merozoite.It is effective to many gram positive bacterias.And do not produce drug resistance between other antibiotic.Maduramicin is a monosaccharide polyethers ionophore type antibiotic.It has stronger affinity to monovalent ions such as potassium, sodium, makes ion imbalance in the coccidiosis cell, causes the coccidiosis Metabolic disorder, and is last dead.Maduramicin is that U.S. cyanogen ammonium company was in exploitation in 1980.It is to be formed by isolating microbial fermentation near the soil Ywma of State of Arizona, US.Its ammonium salt is from the color crystalline powder, and fusing point is 165-167 ℃, and is water insoluble, is dissolved in most of organic solvent.All approved uses such as Brazil, Britain, France and the U.S. at present.Its consumption is little, and is nontoxic to equus.The U.S. FDA regulation: only be used for broiler, feedstuff per ton adds 4.54 grams to 5.45 grams (being 5-6ppm).Withdrawal time 5 days, laying period, forbidden.When the amount of Maduramicin ammonium when 5ppm is above, broiler is eaten the feather phenomenon.When using 6ppm, weightening finish there is harmful effect, and does not improve feed efficiency.
Diclazuril, molecular formula are C
17H
9C
13N
4O
2, molecular weight 407.64, structural formula:
Be off-white color or pale yellow powder, 289～292 ℃ of fusing points, at water, almost insoluble in the ethanol, but be dissolved in aqueous alkali, slightly be dissolved in diformamide, be slightly soluble in oxolane, belong to benzene nitrile latest model wide spectrum anticoccidial drug, be used for the prevention and the treatment of coccidiosis of livestock and poultry, to various important coccidiosiss such as Eimeria tenella, eimeria-type reactor, Eimeria necatrix, Eimeria bucephalae and Eimeria mivati etc. have splendid killing action, its anticoccidial index is respectively (200,200,197,193,183), for preventing and treating one of best medicine of chicken parasitosis in the world at present, to rabbit, the coccidiosis of other beastly fowl such as duck also has good effect.Its characteristics are: 1. dosage is few, the curative effect brilliance, and pest-resistant spectrum is wide.
Coccidiosis DNA is synthetic to can be good at suppressing coccidiosis to diclazuril by disturbing, but Maduramicin uses toxicity too big separately, and the life-time service single medicine easily develops immunity to drugs, and influences the curative effect of coccidiostat.Coccidiostat can not be dissolved in the water mostly, generally add the medium-term and long-term administration of feedstuff to, be unfavorable for using, and the aqueous solvent of coccidiostat adopts ethyl acetate, dimethyl formamide equal solvent mostly at present as prophylactic agent, it is very big to body toxicity, and is unstable behind the medicine dissolution.
Summary of the invention
The object of the invention provides a kind of anticoccidial solution that contains diclazuril and Maduramycin Ammonium and preparation method thereof, to reduce the Drug resistance of coccidiostat, strengthens the curative effect of medicine, the convenient use.
Technical scheme of the present invention is: a kind of anticoccidial solution that contains diclazuril and Maduramycin Ammonium, be the compound recipe water soluble preparation, and comprise diclazuril, Maduramycin Ammonium, triton x-100 and Polyethylene Glycol, Maduramycin Ammonium is the ammonium salt of Maduramicin.
The content range of described diclazuril is 5 to 10 mg/ml, and the content range of described Maduramycin Ammonium is 10 to 20 mg/ml.
Described diclazuril is 1 to 2 with the weight ratio of Maduramycin Ammonium.
The proportioning of described triton x-100 and Polyethylene Glycol is that the volume parts of triton x-100 is 0.5 to 2, and the volume parts of Polyethylene Glycol is 8 to 9.5.
The molecular weight ranges of described Polyethylene Glycol is 200-600.
The molecular weight of described Polyethylene Glycol is 400.
A kind of anticoccidial solution that contains diclazuril and Maduramycin Ammonium and preparation method thereof, Polyethylene Glycol is heated to 100 degrees centigrade to 120 degrees centigrade, add described diclazuril then, after stirring makes the diclazuril dissolving, add described Maduramycin Ammonium, after stirring makes the Maduramycin Ammonium dissolving, add described triton x-100 again, obtain described anticoccidial solution after stirring.
The present invention compared with prior art has the following advantages: the drug regimen that adopts diclazuril and Maduramycin Ammonium, make pest-resistant expanded range, with be difficult for developing immunity to drugs than folk prescription anticoccidiosis medicine ratio, medicament is easy to and the water mixing, easy to use, security reliability is strong, good drug efficacy, and using dosage is reduced to 0.5PPm and is still had significant curative effect (pre-mixing agent must not less than 1PPm).
The anticoccidial drug Maduramicin is extensive use of nearly ten years at home, both at home and abroad the report that once had the Maduramicin drug-resistant worm plant to produce.In addition, the effective dose and the toxic dose of Maduramicin are more approaching, and the report that domestic relevant Maduramicin is poisoned is of common occurrence.In order to improve drug effect, reduce poisoning, the present invention has adopted the drug effect decline and the shortcoming of poisoning that overcomes Maduramicin with nonionic anticoccidial drug diclazuril drug combination, and makes aqueous solvent.
1. materials and methods
1.1 test chicken AA broiler is isolated and is raised in cages to 12 ages in days, at pretest inspection feces, confirms that not infecting coccidiosis uses chicken as test.
1.2 trial drug
Maduramicin; Diclazuril; Compound recipe diclazuril aqueous solution (the present invention); 2.5% hundred ball is clear.
1.3 test grouping
1.3.1 compound recipe diclazuril aqueous solution prevention group
1.3.2 hundred balls prevention group clearly
1.3.3 infect not medication group
1.3.4 do not infect not medication group
Every group 12 plumage amounts to 48 plumage chickens, and random packet, average weight are 175.48 ± 0.18g.
1.4 infected insect species and infective dose are used the E.tenella coccidiosis, except that not infecting not medication group, all the other respectively organize every plumage chicken oral 8 * 10
4Individual spore egg capsule.Check that spirit, appetite, feces change the promoting the circulation of blood of going forward side by side and just keeps the score every day after infection.Collected feces to the 7th day, carry out the egg capsule counting, weighed to cut open in the 8th day and kill, observe caecum lesion and keep the score.
1.5 medication administration method prevention group was given pastille drinking-water in preceding 24 hours in infection.
1.6 drug effect judge index
1.6.1 survival rate (%) survival chicken is counted ÷ and begins chicken number * 100%
1.6.2 the relative weight gain rate medication group or the rate of body weight gain ÷ that infects not medication group do not infect rate of body weight gain * 100% of not medication group
1.6.3 hemafecia is kept the score by Morehouse and Baron standard.
1.6.4 lesion score is pressed Johnson and Reid standard.
1.6.5 average lesion score * 10 of every group of chicken of pathological changes value
1.6.6 gram feces egg sac number (OPG) reference angle field clearing method.
1.6.7 the egg capsule value is by field, angle clearing method.
1.6.8 the anticoccidial index is according to Merck (Merck) company formula: ACI=(the relative weight gain rate+survival rate)-(pathological changes value+egg capsule value)
2. result of the test
Compound recipe diclazuril aqueous solution prevention chicken coccidiosis result of the test
| Grouping | Compound recipe diclazuril aqueous solution prevention group | Hundred balls prevention group clearly | Infect not medication group | Do not infect not medication group |
| Experimental chicken number (plumage) | 12 | 12 | 12 | 12 |
| Age in days (my god) | 12 | 12 | 12 | 12 |
| With concentration (X10 -6) | 1 | 1 | / | / |
| Survival rate (%) | 100 | 100 | 58.0 | 100 |
| Average weight gain (g) | 217.1 | 187.9 | 83.5 | 214.6 |
| The relative weight gain rate (%) | 101.1 | 87.5 | 38.8 | 100.0 |
| Hemafecia keep the score (0 ~ 4) | 0 | 0 | 4 | 0 |
| Pathological changes value (x) | 2 | 1 | 29 | 0 |
| Egg capsule value (x) | 5 | 0 | 40 | 0 |
| ACI | 194.1 | 186.5 | 27.8 | 200 |
Clear 186.5, two the medication groups of the highest 194.1, hundred balls of compound recipe diclazuril aqueous solution anticoccidial index have all reached the significant level of anticoccidial effect in the medication group as can be seen from the table, hemafecia all do not occur for 2 groups from clinical hemafecia.The average weight gain of compound recipe diclazuril aqueous solution group is organized clearly than hundred balls and is improved 15.54%, but the lesion score of compound recipe diclazuril group and egg capsule counting are organized clearly apparently higher than hundred balls.The survival rate of medication group, weightening finish, hemafecia, pathological changes value, egg capsule value and infect not medication group notable difference is arranged.
3. conclusion
Control chicken coccidiosis with medicine and still be present a kind of main method.Because the medicine of prolonged application same type prevents chicken coccidiosis, often causes the generation of drug resistance worm strain, the report of this respect is arranged all both at home and abroad.Present mechanism to the strain of generation drug resistance worm is not studied clear as yet fully, and the method that does not therefore have a kind of basic solution Drug resistance worm strain to produce has only some measures of prevention generation drug resistance worm strain at present.As drug combination or by turns medication and vaccine are used alternatingly.
Make aqueous solvent with the compound recipe diclazuril, not only can be used for the prevention of chicken coccidiosis, can also be used for the treatment of, from this result of the test, it is clear that its anticoccidial index of compound recipe diclazuril aqueous solution is higher than hundred balls.
The specific embodiment
The anticoccidial solution that contains diclazuril and Maduramycin Ammonium involved in the present invention, adopting medicine is diclazuril and Maduramycin Ammonium, the content of described diclazuril is 5 mg/ml, the content of described Maduramycin Ammonium is 10 mg/ml, adopting solvent is triton x-100 and PEG400, the volume parts of triton x-100 is 1, and the volume parts of Polyethylene Glycol is 9, can add an amount of sweeting agent to regulate the taste of this solution in solution.
PEG (Polyethylene Glycol) is the crystallinity water soluble (CO) polymers, the helix that two units are arranged in the per unit in the molecule when the polyethylene glycols medicine solidifies, can comprise the medicine of volume in the matter space between this spiral type, can make the dissolution rate of inclusion very fast during as substrate, drug effect is rapid.The PEG product is nontoxic, nonirritant, have good water solublity, intermiscibility, lubricity, cementability and heat stability.PEG400 is a liquid, it has and the extensive compatibility of all kinds of solvents, is fine solvent and solubilizing agent.The solution that contains PEG is very safe, very stable when being heated to 150 degrees centigrade.
OP-10 (triton x-100) chemical name is a Triton X-100, is a kind of surfactant of excellence, moistening and detergent.Adopt PEG400 and OP-10 as solvent, the dissolubility of Toltrazuril is improved, drug effect increases, and stability of solution strengthens.
Contain the preparation of the anticoccidial solution of diclazuril and Maduramycin Ammonium, be that described Polyethylene Glycol is heated to 110 degrees centigrade, add described diclazuril then, after the stirring and dissolving, add described Maduramycin Ammonium, after stirring and dissolving, add described triton x-100 again, obtain described anticoccidial solution after stirring.
Claims (7)
1, a kind of anticoccidial solution that contains diclazuril and Maduramycin Ammonium, it is characterized in that: it comprises diclazuril, Maduramycin Ammonium, triton x-100 and Polyethylene Glycol.
2, the anticoccidial solution that contains diclazuril and Maduramycin Ammonium according to claim 1, it is characterized in that: the content range of described diclazuril in anticoccidial solution is 5 to 10 mg/ml, and the content range of described Maduramycin Ammonium in anticoccidial solution is 10 to 20 mg/ml.
3, the anticoccidial solution that contains diclazuril and Maduramycin Ammonium according to claim 2 is characterized in that: described diclazuril is 1 to 2 with the weight ratio of described Maduramycin Ammonium in anticoccidial solution.
4, the anticoccidial solution that contains diclazuril and Maduramycin Ammonium according to claim 1, it is characterized in that: described triton x-100 and the Polyethylene Glycol proportioning in anticoccidial solution is that the volume parts of triton x-100 is 0.5 to 2, and the volume parts of Polyethylene Glycol is 8 to 9.5.
5, the anticoccidial solution that contains diclazuril and Maduramycin Ammonium according to claim 1, it is characterized in that: the molecular weight ranges of described Polyethylene Glycol is 200-600.
6, the anticoccidial solution that contains diclazuril and Maduramycin Ammonium according to claim 5, it is characterized in that: the molecular weight of described Polyethylene Glycol is 400.
7, a kind of preparation method that contains the anticoccidial solution of diclazuril and Maduramycin Ammonium, it is characterized in that: Polyethylene Glycol is heated between 100 degrees centigrade to 120 degrees centigrade, add described diclazuril then, after stirring makes the diclazuril dissolving, add described Maduramycin Ammonium, after stirring makes the Maduramycin Ammonium dissolving, add described triton x-100 again, obtain described anticoccidial solution after stirring.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102331405A (en) * | 2011-05-30 | 2012-01-25 | 濮阳泓天威药业有限公司 | Detection method for titer of maduramicin fermentation medium |
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2006
- 2006-01-24 CN CN 200610038078 patent/CN1839879A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102331405A (en) * | 2011-05-30 | 2012-01-25 | 濮阳泓天威药业有限公司 | Detection method for titer of maduramicin fermentation medium |
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