CN104161725A - Arprinocide nano-emulsion for coccidium resistance and preparation method thereof - Google Patents

Arprinocide nano-emulsion for coccidium resistance and preparation method thereof Download PDF

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Publication number
CN104161725A
CN104161725A CN201310391363.8A CN201310391363A CN104161725A CN 104161725 A CN104161725 A CN 104161725A CN 201310391363 A CN201310391363 A CN 201310391363A CN 104161725 A CN104161725 A CN 104161725A
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China
Prior art keywords
nanoemulsions
anticoccidial
arprinocide
nano
emulsion
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CN201310391363.8A
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Chinese (zh)
Inventor
李亚娥
陈建晖
张听盼
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Zhengzhou Houyi Pharmaceutical Co Ltd
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Zhengzhou Houyi Pharmaceutical Co Ltd
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Priority to CN201310391363.8A priority Critical patent/CN104161725A/en
Publication of CN104161725A publication Critical patent/CN104161725A/en
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Abstract

The invention discloses an arprinocide nano-emulsion for coccidium resistance and a preparation method thereof. The arprinocide nano-emulsion for coccidium resistance comprises, by weight, 0.1-10% of arprinocide, 24.0-35% of a surfactant, 0.2-22% of a surfactant assistant, 1.0-8.0% of a cosolvent, 1.5-10% of oil and the balance distilled water. The arprinocide nano-emulsion for coccidium resistance has small suspension particle sizes of 1-100nm, high particle distribution uniformity and good stability. In use, the arprinocide nano-emulsion can be directly mixed with drinking water for poultry, is not precipitated and separated and is convenient for use. The arprinocide nano-emulsion has strong palatability, small irritation to the poultry, improves bioavailability of the drug active components, improves drug effects, solves the problem of drug waste in use and reduces a drug use cost.

Description

A kind of MK-302 nanoemulsions and preparation method thereof for anticoccidial
Technical field
The invention belongs to veterinary drug technical field, be specifically related to a kind of anticoccidial MK-302 nanoemulsions, also relate to the preparation method of anticoccidial MK-302 nanoemulsions simultaneously.
Background technology
Coccidiosis is the caused parasitic protozoa disease of enterocyte that is parasitized chicken by one or more coccidiosiss of Eimeria, parasite breeds at double in small intestinal, cause body tissue damage, reduce the absorbance of nutrient in feed intake and feedstuff, cause body dehydration and blood loss, finally cause poultry meat egg to be produced and occur heavy losses.
At present, the key for the treatment of chicken coccidiosis is how to solve serious drug resistance problem.And MK-302 is chemosynthesis coccidiostat of new generation, its primary structure is different from other coccidiostats, with other coccidiostats without cross resistance; MK-302 is brought into play anticoccidial effect by the purine metabolism that disturbs coccidiosis; Its coccidiostat activity mainly concentrates on the agamocytogeny of coccidiosis, and the Sporulated of egg capsule is also had to certain inhibitory action.
Confirm after deliberation, MK-302 has wide spectrum coccidiostat activity, to the multiple Eimeria of chicken, as Eimeria tenella, fragile Eimeria, Eimeria Necatrix, Eimeria maxima, heap type Eimeria, E.brunetti all have stronger inhibition and killing action, it is the anticoccidial drug of a kind of efficient, wide spectrum, low toxicity.But because MK-302 is water insoluble, existence and stability is poor in use, bioavailability is lower, drug effect is low, waste serious problem to cause it.
Summary of the invention
The object of this invention is to provide a kind of MK-302 nanoemulsions of the anticoccidial with good stability and bioavailability.
Second object of the present invention is to provide the preparation method of a kind of anticoccidial MK-302 nanoemulsions.
In order to realize above object, the technical solution adopted in the present invention is: a kind of anticoccidial MK-302 nanoemulsions, component by following percentage by weight forms: MK-302 0.1%~10%, surfactant 24.0%~35%, cosurfactant 0.2%~22%, cosolvent 1.0%~8.0%, oil 1.5%~10%, surplus is distilled water.
Described surfactant is triton x-100, castor oil polyoxyethylene ether (EL40) or polyoxyethylene hydrogenated Oleum Ricini (RH40).
Described cosurfactant is dehydrated alcohol or isopropyl alcohol (IPM).
Described cosolvent is glacial acetic acid or formic acid.
Described oil is Jojoba oil or isopropyl propionate.
A preparation method for MK-302 nanoemulsions for above-mentioned anticoccidial, comprises the following steps:
1) by surfactant, cosurfactant and cosolvent mix homogeneously, obtain mixture;
2) in step 1) gained mixture, add MK-302 and oil simultaneously, after mix homogeneously, access while stirring distilled water, be stirred to the system that forms homogeneous transparent, to obtain final product.
Nanoemulsions (nanoemulsion) claims again microemulsion (microemulsion), to be formed by water, oil, surfactant and cosurfactant etc., particle diameter is Thermodynamically stable, the isotropism of 1~100nm, transparent or semitransparent homodisperse system.Nano-emulsion has the unrivaled advantage of many other preparations: 1. for isotropic transparency liquid, belong to thermodynamically metastable fixed system, through pressure sterilizing or centrifugally can not make it layering; 2. technique is simple, and preparation process does not need special installation, and nano-emulsion particle diameter is generally 1~100nm; 3. viscosity is low, the pain can reduce injection time; 4. there is slow release and targeting; 5. improve the dissolubility of medicine, reduce medicine enzymolysis in vivo, can form the protective effect to medicine and improve the absorption of gastrointestinal tract to medicine, improve the bioavailability of medicine.
Anticoccidial of the present invention MK-302 nanoemulsions, particle particle diameter is 1~100nm, grain diameter is little, be evenly distributed, and has good stability; When use, can directly mix with the drinking water of poultry, without precipitating and separating out, easy to use; Palatability is strong, little to the zest of poultry; Improve the bioavailability of active constituents of medicine, improved the curative effect of medicine, solved the problem of drug waste while use, reduced drug cost.The preparation method of MK-302 nanoemulsions for anticoccidial of the present invention, technique is simple, easy to operate, is applicable to large-scale industrialization and produces.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is further illustrated.
Embodiment 1
The anticoccidial of the present embodiment MK-302 nanoemulsions, is made up of the component of following percentage by weight: MK-302 3%, triton x-100 35%, dehydrated alcohol 22%, glacial acetic acid 5%, Jojoba oil 6%, surplus is distilled water.
The preparation method of MK-302 nanoemulsions for the anticoccidial of the present embodiment, comprises the following steps:
1) by triton x-100, dehydrated alcohol and glacial acetic acid mix homogeneously, obtain mixture;
2) in step 1) gained mixture, add MK-302 and Jojoba oil simultaneously, after mix homogeneously, access while stirring distilled water, be stirred to the system that forms homogeneous transparent, to obtain final product.
Embodiment 2
The anticoccidial of the present embodiment MK-302 nanoemulsions, is made up of the component of following percentage by weight: MK-302 6%, castor oil polyoxyethylene ether (EL40) 28%, isopropyl alcohol 12%, formic acid 8%, Jojoba oil 5%, surplus is distilled water.
The preparation method of MK-302 nanoemulsions for the anticoccidial of the present embodiment, comprises the following steps:
1) by castor oil polyoxyethylene ether (EL40), isopropyl alcohol and formic acid mix homogeneously, obtain mixture;
2) in step 1) gained mixture, add MK-302 and Jojoba oil simultaneously, after mix homogeneously, access while stirring distilled water, be stirred to the system that forms homogeneous transparent, to obtain final product.
Embodiment 3
The anticoccidial of the present embodiment MK-302 nanoemulsions, is made up of the component of following percentage by weight: MK-302 0.1%, castor oil polyoxyethylene ether (EL40) 31%, isopropyl alcohol 10%, formic acid 1%, isopropyl propionate (IPM) 1.5%, surplus is distilled water.
The preparation method of MK-302 nanoemulsions for the anticoccidial of the present embodiment, comprises the following steps:
1) by castor oil polyoxyethylene ether (EL40), isopropyl alcohol and formic acid mix homogeneously, obtain mixture;
2) in step 1) gained mixture, add MK-302 and isopropyl propionate (IPM) simultaneously, after mix homogeneously, access while stirring distilled water, be stirred to the system that forms homogeneous transparent, to obtain final product.
Embodiment 4
The anticoccidial of the present embodiment MK-302 nanoemulsions, component by following percentage by weight forms: MK-302 10%, polyoxyethylene hydrogenated Oleum Ricini (RH40) 24%, isopropyl alcohol 0.2%, formic acid 7%, isopropyl propionate (IPM) 10%, surplus is distilled water.
The preparation method of MK-302 nanoemulsions for the anticoccidial of the present embodiment, comprises the following steps:
1) by polyoxyethylene hydrogenated Oleum Ricini (RH40), isopropyl alcohol and formic acid mix homogeneously, obtain mixture;
2) in step 1) gained mixture, add MK-302 and isopropyl propionate (IPM) simultaneously, after mix homogeneously, access while stirring distilled water, be stirred to the system that forms homogeneous transparent, to obtain final product.
Experimental example
This experimental example detects the curative effect of chicken coccidiosis with MK-302 nanoemulsions embodiment 1~3 gained anticoccidial, and test method is as follows:
Experimental subject: 180 of the meat sold on the market chickling of 15 age in days non-ball worm capsule ovum, 280 ± 1.8 grams of body weight, are divided into 6 groups, 30 every group;
For trying egg capsule: Eimeria tenella egg capsule, every chicken infective dose is 2.0 × 10 5individual mixing egg capsule.
Crude drug group: MK-302 material medicine matched group, mixed feeding, 0.08g spice 1kg, after infecting the 1st day starts administration, is used in conjunction 7 days.
Test group 1: embodiment 1 sample, mixed drink, 0.5ml is watered 1L, infects and starts one day after medication, is used in conjunction 7 days.
Test group 2: embodiment 2 samples, mixed drink, 0.5ml is watered 1L, infects and starts one day after medication, is used in conjunction 7 days.
Test group 3: embodiment 3 samples, mixed drink, 0.5ml is watered 1L, infects and starts one day after medication, is used in conjunction 7 days.
Test group 4: embodiment 4 samples, mixed drink, 0.5ml is watered 1L, infects and starts one day after medication, is used in conjunction 7 days.
Positive controls: do not add any coccidiostat after infection.
Experimental result sees the following form 1:
MK-302 nanoemulsions examination of curative effect result for table 1 embodiment 1~3 gained anticoccidial
As can be seen from Table 1: aspect weightening finish, except positive controls, it is all better that all the other respectively organize chicken average weight gain, and test group is compared with crude drug group, and MK-302 nanoemulsions has good gaining effect; MK-302 nanoemulsions is the eliminating of infection control chicken coccidial oocyst effectively, avoids the damage to chicken body intestinal, has significant curative effect for chicken coccidiosis; Except positive controls, respectively organize anticoccidial index all higher than 180, and the anticoccidial index of MK-302 nanoemulsions is greater than 185, belong to efficient coccidiostat, show better coccidiostat activity with respect to MK-302 crude drug group.

Claims (6)

1. an anticoccidial MK-302 nanoemulsions, it is characterized in that: the component by following percentage by weight forms: MK-302 0.1%~10%, surfactant 24.0%~35%, cosurfactant 0.2%~22%, cosolvent 1.0%~8.0%, oil 1.5%~10%, surplus is distilled water.
2. anticoccidial according to claim 1 MK-302 nanoemulsions, is characterized in that: described surfactant is triton x-100, castor oil polyoxyethylene ether or polyoxyethylene hydrogenated Oleum Ricini.
3. anticoccidial according to claim 1 MK-302 nanoemulsions, is characterized in that: described cosurfactant is dehydrated alcohol or isopropyl alcohol.
4. anticoccidial according to claim 1 MK-302 nanoemulsions, is characterized in that: described cosolvent is glacial acetic acid or formic acid.
5. anticoccidial according to claim 1 MK-302 nanoemulsions, is characterized in that: described oil is Jojoba oil or isopropyl propionate.
6. a preparation method for MK-302 nanoemulsions for anticoccidial as claimed in claim 1, is characterized in that: comprise the following steps:
1) by surfactant, cosurfactant and cosolvent mix homogeneously, obtain mixture;
2) in step 1) gained mixture, add MK-302 and oil simultaneously, after mix homogeneously, access while stirring distilled water, be stirred to the system that forms homogeneous transparent, to obtain final product.
CN201310391363.8A 2013-08-30 2013-08-30 Arprinocide nano-emulsion for coccidium resistance and preparation method thereof Pending CN104161725A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102525919A (en) * 2011-11-28 2012-07-04 河南牧翔动物药业有限公司 Decoquinate nanoemulsion coccidium-resisting drug and preparation method thereof
CN102973504A (en) * 2012-10-30 2013-03-20 河南牧翔动物药业有限公司 Adprin nano-emulsion anticoccidial drug and preparation process thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102525919A (en) * 2011-11-28 2012-07-04 河南牧翔动物药业有限公司 Decoquinate nanoemulsion coccidium-resisting drug and preparation method thereof
CN102973504A (en) * 2012-10-30 2013-03-20 河南牧翔动物药业有限公司 Adprin nano-emulsion anticoccidial drug and preparation process thereof

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Application publication date: 20141126