CN111759802A - Compound fraxidin suspension and preparation and application thereof - Google Patents
Compound fraxidin suspension and preparation and application thereof Download PDFInfo
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Abstract
The invention provides a compound frainer suspension, wherein each 100ml of the compound frainer suspension contains 0.5-5g of frainer, 0.05-2g of praziquantel, 805-30g of tween-805, 2-15ml of ethanol, 10-50g of dimethyl sulfoxide and the balance of water, and also provides a preparation method and application of the compound frainer suspension. The compound fraxidin suspension and the preparation and the application thereof have the advantages of simple preparation method, stable property, easy redispersion and obvious effect, effectively solve the stability of the fraxidin after being dissolved in water, expand the insect expelling spectrum of the fraxidin and are suitable for large-scale industrial production and clinical use.
Description
Technical Field
The invention belongs to the field of pesticide preparation, and particularly relates to a compound frataxin suspension as well as preparation and application thereof.
Background
Frauran (Fluralaner), belonging to isoxazoline insecticides, is a novel high-efficiency insecticide, and dies by interfering with the parasite's gamma-aminobutyric acid (GABA) gated chloride channel leading to its nervous system hyperexcitation. Compared with the traditional insecticide, the isoxazoline insecticide has obvious differences in the aspects of target, molecular structure, selectivity and the like. The isoxazoline pesticide is mainly used for treating parasites of pet cats or dogs, such as fleas, ticks, red mites of poultry and the like.
Praziquantel belongs to an anthelmintic. Praziquantel has broad-spectrum anti-schistosome and anti-tapeworm effects. Has extremely high activity to various tapeworm adults and good activity to larvae. The mechanism of action of praziquantel is the spasmodic contraction of the parasite muscle system and the rapid formation of vacuoles in the syncytial cortex. In addition, praziquantel may also have 5-hydroxytryptamine-like effect on schistosome, causing spastic paralysis of the body.
Patent application No.: 201480068597.1, title of the invention: use of isoxazoline derivatives for the treatment or prevention of arthropod infestations in poultry, the flurarana formulations provided herein are effective in the treatment or prevention of ectoparasites in poultry animals.
Patent application No.: 201680036814.8, title of the invention: the invention provides a flurarana preparation which can prevent isoxazoline from being degraded when hypochlorite is used for disinfecting drinking water and improve the application range of the flurarana.
Patent application No.: 201110342866.7 title of the invention: the invention provides a compound avermectin suspension for expelling and treating livestock endoparasites and a preparation method thereof.
However, although considerable progress has been made in the research of pesticides in and out of animals, due to the generation of drug resistance of parasites, the application effect of the existing pesticides is weakened year by year, the dosage of the pesticides has to be increased, which not only causes the increase of cost, but also causes environmental pollution, and therefore, it is necessary to develop a novel compound preparation for clinical application.
In addition, compared with in-vitro drops/pour-on preparations, the oral insecticide has less harm to the environment and human after being discharged from the body through metabolism in animals.
Disclosure of Invention
In view of the above, the invention aims to provide a compound frataxin suspension and preparation and application thereof, the preparation method is simple, the property is stable, the redispersion is easy, the effect is obvious, the stability of the frataxin after being dissolved in water is effectively solved, the insect-repellent spectrum of the frataxin is expanded, and the compound frataxin suspension is suitable for large-scale industrial production and clinical use.
In order to achieve the purpose, the technical scheme of the invention is realized as follows:
a compound frainer suspension comprises 0.5-5g frainer, 0.05-2g praziquantel, 805-30g tween-30 g, 2-15ml ethanol, 10-50g dimethyl sulfoxide and the balance water per 100ml compound frainer suspension.
Furthermore, each 100ml of compound fradoramesodium suspension contains 1g of fradoramesodium, 0.2g of praziquantel, tween-8014 g, 7ml of ethanol, 25g of dimethyl sulfoxide and the balance of water.
Further, the volume ratio of the mass of the tween-80 to the ethanol is 2: 1.
Further, the particle sizes of the frataxine and the praziquantel are both less than 20 mu m.
A preparation method of compound fraxidin suspension comprises the following steps:
(1) dissolving the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) mixing ethanol, tween-80 and purified water;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, and separating out a mixture of the frataxin and the praziquantel to obtain the compound frataxin suspension.
Further, the heating rate in the step (3) is 3 ℃/min, and the heating temperature is 55-60 ℃.
Further, in the step (3), stirring is carried out by using a stirring paddle, the radius of the stirring paddle is not less than 10cm, and the stirring speed is 90-120 r/min.
The compound frainer suspension is shaken uniformly and then is directly taken orally or added into drinking water for drinking, and is used for preventing and treating internal and external parasites of livestock, poultry and pets.
Compared with the prior art, the compound frataxin suspension and the preparation and application thereof have the following advantages:
(1) the compound fraxidin suspension is simple in preparation method, stable in property, easy to redisperse and remarkable in effect, effectively solves the problem of stability of fraxidin after being dissolved in water, expands the insect-repellent spectrum of fraxidin, and is suitable for large-scale industrial production and clinical use.
(2) The compound frainer suspension can be mixed with water in any ratio, and the clinical application range of the compound frainer suspension is greatly expanded.
(3) The compound fraxidin suspension can be used for preventing and treating internal and external parasites of animals such as cattle, pigs, sheep, poultry, dogs, wool and the like, expands the insect-repelling spectrum of fraxidin and praziquantel, simplifies the insect-repelling mode and meets the clinical requirement.
(4) The compound frataxin suspension has simple process, easily obtained raw materials of all components, greatly reduced production cost and suitability for modern mass production.
(5) The compound fradora sodium suspension has the best stability in a system with the volume ratio of the mass of the tween-80 to the volume of the ethanol being 2: 1. The heating temperature is 55-60 ℃, the stirring speed is 90-120r/min, the particle size of the precipitated raw material is less than 20 mu m, the operation of grinding, crushing or homogenizing is not needed, the steps are simplified, the energy consumption is saved, and the production cost is greatly reduced.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the invention without limitation. In the drawings:
FIG. 1 is a particle size diagram of a compound fraxidin suspension described in inventive example 1 of the present invention;
FIG. 2 is a particle size diagram of a compound fraxidin suspension described in inventive example 2 of the present invention;
FIG. 3 is a particle size diagram of a compound fraxidin suspension according to inventive example 3;
FIG. 4 is a particle size diagram of a compound fraxidin suspension described in inventive example 4 of the present invention;
FIG. 5 is a particle size diagram of a compound fraxidin suspension according to the invention, as described in example 5;
FIG. 6 is a particle size diagram of a compound fraxidin suspension according to the invention as described in example 6;
FIG. 7 is a particle size diagram of a compound fraxidin suspension according to the invention as described in example 7;
FIG. 8 is a particle size diagram of a compound fraxidin suspension according to the invention, as described in example 8;
figure 9 is a particle size diagram of a compound fraxidin suspension described in inventive example 9.
Detailed Description
It should be noted that the embodiments and features of the embodiments of the present invention may be combined with each other without conflict.
The invention will be described in detail with reference to the following examples.
Example 1
A compound fraxidin suspension comprises 1g fraxidin, 0.1g praziquantel, tween-8030 g, 15ml ethanol, 20g dimethyl sulfoxide, and water to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol, tween-80 and purified water in the mass/volume ratio;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, controlling the temperature at 55-60 ℃, and stirring at the speed of 100r/min, and obtaining the compound frailamide suspension of the components after the mixture of the frailamide and the praziquantel is separated out.
Example 2
A compound fraxidin suspension comprises 5g fraxidin, 1g praziquantel, tween-8020 g, 10ml ethanol, 40g dimethyl sulfoxide, and purified water to make up to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol, tween-80 and purified water with the mass or volume;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, controlling the temperature at 55-60 ℃, and stirring at the speed of 120r/min, and obtaining the compound fradoramesodium suspension of the components after the mixture of the fradoramesodium and the praziquantel is separated out.
Example 3
A compound fraxidin suspension comprises 3.2g fraxidin, 0.6g praziquantel, Tween-8012 g, 6ml ethanol, 25g dimethyl sulfoxide, and purified water to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol, tween-80 and purified water with the mass or volume;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, controlling the temperature to be 55-60 ℃, and stirring at the speed of 115r/min to obtain the compound fradoramesodium suspension after the mixture of the fradoramesodium and the praziquantel is separated out.
Example 4
A compound frataxine suspension comprises 0.5g frataxine, 0.05g praziquantel, tween-8020 g, 15ml ethanol, 20g dimethyl sulfoxide, and purified water to make up to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol, tween-80 and purified water with the mass or volume;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, controlling the temperature at 55-60 ℃, and stirring at the speed of 100r/min, and obtaining the compound frainer suspension of the components after the mixture of the frainer and the praziquantel is separated out.
Example 5
A compound fraxidin suspension comprises 1g fraxidin, 0.1g praziquantel, tween-8030 g, 10ml ethanol, 20g dimethyl sulfoxide, and purified water to make up to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol and the Tween-80 purified water according to the mass or volume;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, controlling the temperature to be 55-60 ℃, and stirring at the speed of 100r/min to obtain the compound frainer suspension of the components after the mixture of the frainer and the praziquantel is separated out.
Example 6
A compound fraxidin suspension comprises 1g fraxidin, 0.1g praziquantel, Tween-8015 g, 15ml ethanol, 20g dimethyl sulfoxide, and purified water to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol and the Tween-80 purified water according to the mass or volume;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, controlling the temperature at 55-60 ℃, and stirring at the speed of 100r/min, and obtaining the compound frainer suspension of the components after the mixture of the frainer and the praziquantel is separated out.
Example 7
A compound fraxidin suspension comprises 1g fraxidin, 0.1g praziquantel, Tween-8010 g, 30ml ethanol, 20g dimethyl sulfoxide, and purified water to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol and the Tween-80 purified water according to the mass or volume;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, controlling the temperature at 55-60 ℃, and stirring at the speed of 100r/min, and obtaining the compound frainer suspension of the components after the mixture of the frainer and the praziquantel is separated out.
Example 8
A compound fraxidin suspension comprises 1g fraxidin, 0.1g praziquantel, tween-8030 g, 15ml ethanol, 20g dimethyl sulfoxide, and purified water to make up to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol and the Tween-80 purified water according to the mass or volume;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2), slowly heating, controlling the temperature at 45-50 ℃, stirring at the speed of 100r/min, and obtaining the compound frataxin suspension of the components after the mixture of the frataxin and the praziquantel is separated out.
Example 9
A compound fraxidin suspension comprises 1g fraxidin, 0.1g praziquantel, tween-8030 g, 15ml ethanol, 20g dimethyl sulfoxide, and purified water to make up to 100 ml.
The preparation method of the compound fraxidin suspension comprises the following steps:
(1) dissolving the mass of the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) uniformly mixing the ethanol and the Tween-80 purified water according to the mass or volume;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, controlling the temperature at 65-70 ℃, and stirring at the speed of 100r/min, and obtaining the compound frainer suspension of the components after the mixture of the frainer and the praziquantel is separated out.
The following tests were carried out on the compound frataxin suspension obtained above to prove the beneficial effects of the present invention:
(1) stability test
(A) High temperature test
The suspensions prepared in the embodiments 1, 5, 6 and 7 of the present invention are placed at 60 ℃ for 10 days, and sampled on the 10 th day to detect the relevant indexes, and the results are as follows:
TABLE 1 list of the test results of the high temperature test
(B) Accelerated test
The suspensions obtained in examples 1 and 5 of the present invention were subjected to a test at 40. + -. 2 ℃ and RH 75. + -. 5% for 6 months. Samples are taken at the end of 0 and 6 months in the test period to detect relevant indexes, and the results are as follows:
TABLE 2 test result list of accelerated test
Stability test researches show that in the process of the investigation, all indexes of the suspension in example 1 are changed slightly, the change range conforms to relevant regulations, and in the four examples, only the proportions of tween and ethanol are different, and the dosages of the other main medicines and auxiliary materials are consistent, which indicates that the stability of the suspension is the best only in a system with the mass of tween-80 and the volume of ethanol being 2: 1.
(2) Particle size detection test
The suspensions in the above examples were tested according to the particle size determination method in the appendix of the "Chinese veterinary pharmacopoeia", with the following results:
table 3 table of results of viscosity testing
| Group of | Particle size distribution |
| Example 1 | 100％＜20μm |
| Example 2 | 100％＜20μm |
| Example 3 | 100％＜20μm |
| Example 4 | 99％＜20μm |
| Example 5 | 95％＜20μm |
| Example 6 | 97％＜20μm |
| Example 7 | 98％＜20μm |
| Example 8 | 90％＜20μm |
| Example 9 | 85％＜20μm |
The results show that the particle size of the precipitated raw material is 100% below 20 μm in a system with the mass of Tween-80 and the volume of ethanol being 2:1 under the conditions of 55-60 ℃ and stirring speed of 90-120 r/min.
(3) Antiparasitic efficacy test
Antiparasitic efficacy tests were performed on the fraxidin compound suspension prepared in example 1, and on commercially available praziquantel powder and exzol (fraxidin solution, moschaton, france).
5000 laying hens infected with poultry red mites and tapeworm (280 days old) are selected in a certain laying hen farm in Huadu city, Guangdong province and divided into 5 groups, the group A uses the praziquantel powder in the example 1, the group B uses the praziquantel powder, the group C uses the EXZOLT, the group D uses the praziquantel powder and the EXZOLT, the group E does not use the drug as a blank group, and on the 5 th day after the drug administration, feces are collected for microscopic examination and the egg laying rate and the feed intake before and after the drug administration are recorded.
TABLE 4 antiparasitic efficacy test data tabulation
Wherein, the egg reduction rate is (number of eggs before drug administration-number of eggs after drug administration)/number of eggs before drug administration is multiplied by 100%.
As can be seen from the above table, compared with the existing commercially available products, the compound fradoramex suspension prepared by the invention has obviously improved antiparasitic effect no matter used in combination or singly, and no adverse reaction occurs to animals in the process of using the compound fradoramex suspension, which indicates that the preparation has high safety and curative effect.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the invention, so that any modifications, equivalents, improvements and the like, which are within the spirit and principle of the present invention, should be included in the scope of the present invention.
Claims (8)
1. A compound fraxidin suspension is characterized in that: every 100ml of compound fraxidin suspension contains 0.5-5g of fraxidin, 0.05-2g of praziquantel, 805-30g of tween-15 ml of ethanol, 10-50g of dimethyl sulfoxide and the balance of water.
2. The compound fraxidin suspension according to claim 1, wherein: each 100ml of compound frailamide suspension contains 1g of frailamide, 0.2g of praziquantel, 8014g of tween-ethanol 7ml, 25g of dimethyl sulfoxide and the balance of water.
3. The compound fraxidin suspension according to claim 1, wherein: the volume ratio of the mass of the Tween-80 to the ethanol is 2: 1.
4. The compound fraxidin suspension according to claim 1, wherein: the particle sizes of the frataxine and the praziquantel are both less than 20 mu m.
5. A method of preparing the compound fraxidin suspension of any one of claims 1-4, characterized by: the method comprises the following steps:
(1) dissolving the fraxidin and the praziquantel in dimethyl sulfoxide;
(2) mixing ethanol, tween-80 and purified water;
(3) and (3) slowly adding the solution obtained in the step (1) into the solution obtained in the step (2) under the stirring condition, slowly heating, and separating out a mixture of the frataxin and the praziquantel to obtain the compound frataxin suspension.
6. The method for preparing the compound fraxidin suspension according to claim 5, wherein the method comprises the following steps: the heating rate in the step (3) is 3 ℃/min, and the heating temperature is 55-60 ℃.
7. The method for preparing the compound fraxidin suspension according to claim 5, wherein the method comprises the following steps: in the step (3), stirring is carried out by using a stirring paddle, the radius of the stirring paddle is not less than 10cm, and the stirring speed is 90-120 r/min.
8. The application of the compound frataxin suspension is characterized in that: the compound frainer suspension of any one of claims 1-4 is shaken and then taken orally directly or added into drinking water for drinking, and is used for preventing and treating internal and external parasites of livestock, poultry and pets.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116726045A (en) * | 2023-06-30 | 2023-09-12 | 重庆汉佩生物科技有限公司 | Florarana composition |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116726045A (en) * | 2023-06-30 | 2023-09-12 | 重庆汉佩生物科技有限公司 | Florarana composition |
| CN116726045B (en) * | 2023-06-30 | 2024-03-19 | 重庆汉佩生物科技有限公司 | Florarana composition |
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