Niclosamide ethanolamine slow-release water dispersible granule and preparation process thereof

Abstract

The invention discloses a niclosamide ethanolamine slow-release water dispersible granule and a preparation process thereof, and belongs to the technical field of niclosamide ethanolamine. A preparation process of the prepared niclosamide ethanolamine slow-release water dispersible granule comprises the following steps: preparing the niclosamide ethanolamine microcapsule; preparing solid powder; and preparing the niclosamide ethanolamine slow-release water dispersible granules. The prepared niclosamide ethanolamine microcapsule has hydrophobicity by using the acrylic acid monomer with a hydrophobic group, the microcapsule has the protection property, so that the microcapsule not only has a slow release effect, but also can resist rain wash, and the added 4-hydroxyphenylacetic acid is used as a sex pheromone for attracting male ampullaria gigas, so that the effect of attracting the male ampullaria gigas is achieved. And a good pomacea canaliculata killing effect can be achieved.

Description

Technical Field

[0001] The invention belongs to the technical field of molluscicidal ethanolamine salts, and specifically relates to a molluscicidal ethanolamine salt sustained-release water-dispersible granule and a preparation process thereof. Background Art

[0002] Snail-killing amine is an internationally recommended snail-killing drug that can be used on site. Since it is insoluble in water, which affects the snail-killing effect, it is generally made into snail-killing amine ethanolamine salt. Snail-killing amine ethanolamine salt is an amide compound with CAS number 1420-04-8. The pure product is yellow crystals. It is the most widely used snail-killing drug at present. It has high stability to heat and is a molluscicide with strong contact and stomach poisoning effects. It has a strong killing effect on adult snails, snail eggs, schistosoma cercariae and hairy butterflies, and the effect is rapid and the drug effect is long-lasting. Snail-killing amine ethanolamine salt has become the world-recognized first-choice drug for killing snails and preventing and controlling schistosomiasis because of its strong snail-killing effect and low toxicity to mammals, and is used as an anthelmintic in clinical practice. Within the snail-killing dosage, it is relatively safe for humans and animals.

[0003] The main dosage forms of molluscicide ethanolamine salt are wettable powder and water suspension. Wettable powder has the problem of dust flying during production and use and uneven distribution of product granules; water suspension itself is a thermodynamically unstable system with poor long-term storage stability. Water-dispersible granules, also known as dry suspension, are one of the pesticide dosage forms. They are made by dehydrating water suspensions. When used, they can be diluted with water to become a suspension that is the same as water suspension. Water-dispersible granules have the common advantages of wettable powders and water suspensions. They disintegrate and disperse quickly in water, and the formed liquid particles are fine and reasonably distributed in size ratio. The suspension rate and stability are higher, and the unit mass of the drug has a wide coverage on the target surface and strong adhesion to the target surface; it can not only ensure the rapid effect and long-term effect of the drug, but also ensure that the drug can fully and completely contact with the target, thereby improving the efficacy. In addition, water-dispersible granules are stable in long-term storage, easy to transport and store, and no dust is generated during use, which is convenient and safe.

[0004] However, the above dosage forms are afraid of being washed away by rainwater during application. Therefore, it is necessary to provide a sustained-release water-dispersible granule of molluscicide ethanolamine salt with the ability to resist rainwater washing and a preparation process thereof. Summary of the invention

[0005] The purpose of the present invention is to provide a sustained-release water-dispersible granule of molluscicide ethanolamine salt and a preparation process thereof, so as to solve the problem that various dosage forms of molluscicide ethanolamine salt in the background technology are afraid of being washed away by rainwater.

[0006] The purpose of the present invention can be achieved through the following technical solutions:

[0007] A preparation process of molluscicide ethanolamine salt sustained-release water-dispersible granules, the operating steps of which are:

[0008] Step (1): preparation of molluscicide ethanolamine salt microcapsules;

[0009] Step (2): preparing solid powder;

[0010] Step (3): Preparation of sustained-release water-dispersible granules of molluscicide ethanolamine salt.

[0011] The molluscicide ethanolamine salt microcapsules include the following preparation steps:

[0012] The molluscicide ethanolamine salt, 4-hydroxyphenylacetic acid, deionized water and anhydrous ethanol are mixed, and the pH thereof is adjusted to 7.4, as the aqueous phase, and stirred. Triolein and Span-85 are mixed to form an oil phase. The aqueous phase is added dropwise to the oil phase and ultrasonically emulsified at room temperature. Then, butyl cyanoacrylate and 2-dodecyl acrylate are added dropwise to the emulsion under stirring, and after polymerization, centrifugation is performed to obtain molluscicide ethanolamine salt microcapsules.

[0013] Furthermore, the dosage ratio of the molluscicide ethanolamine salt, 4-hydroxyphenylacetic acid, deionized water, anhydrous ethanol, triolein, Span-85, butyl cyanoacrylate and 2-dodecyl acrylate is 0.5g:0.3g:20mL:20mL:16g:3g:0.1mL:0.1mL.

[0014] Furthermore, the pH adjustment uses a 0.1 mol / L NaOH aqueous solution.

[0015] Furthermore, the preparation of the solid powder comprises the following preparation steps:

[0016] SP-27001 dispersant, lignin sulfonate, sodium dodecyl sulfate, citric acid, white carbon black and calcined kaolin are mixed, ultrafinely ground and sieved to obtain a solid powder.

[0017] Furthermore, the mass ratio of the SP-27001 dispersant, lignin sulfonate, sodium dodecyl sulfate, citric acid, white carbon black and calcined kaolin is 200:250:10:5:35:500.

[0018] Furthermore, the SP-27001 dispersant was purchased from Jiangsu Qingyu Chemical Technology Co., Ltd.

[0019] Furthermore, the ultrafine grinding has a grinding degree of 99-99.9%.

[0020] Furthermore, the screening is through a 400-600 mesh sieve.

[0021] Furthermore, the molluscicide ethanolamine salt sustained-release water-dispersible granules include the following preparation steps:

[0022] The molluscicide ethanolamine salt microcapsules obtained in step (1) are mixed evenly with the solid powder obtained in step (2), and then a polyvinyl alcohol aqueous solution is added and mixed evenly. The material is sent to an extrusion granulator for granulation, drying and sieving to obtain molluscicide ethanolamine salt sustained-release water-dispersible granules.

[0023] Furthermore, the dosage ratio of the molluscicidal ethanolamine salt microcapsules, the solid powder and the polyvinyl alcohol aqueous solution is 87.5g:938.8g:200mL.

[0024] Furthermore, the mass fraction of the polyvinyl alcohol aqueous solution is 0.5-5%.

[0025] Furthermore, a molluscicide ethanolamine salt sustained-release water-dispersible granule is prepared by the above preparation method.

[0026] Beneficial effects of the present invention:

[0027] 1. The present invention uses acrylic monomers with long hydrophobic side chains to make the synthesized molluscicide ethanolamine salt microcapsules inherently hydrophobic. In conjunction with the standardized application of pesticides by pesticide applicators, the molluscicide ethanolamine salt microcapsules can have certain water resistance during the suspension and dispersion process. Combined with the encapsulation and protection properties of the microcapsules themselves, the molluscicide ethanolamine salt microcapsules have a certain ability to resist rain erosion.

[0028] 2. The present invention uses molluscicide ethanolamine salt as the inner core, and further synthesizes it into microcapsules through the preparation of water-in-oil capsules. Due to the presence of the microcapsule wall, the molluscicide ethanolamine salt microcapsules have the function of sustained-release molluscicide ethanolamine salt.

[0029] 3. The present invention adopts 4-hydroxyphenylacetic acid as the sex pheromone of male golden apple snails to attract male golden apple snails. Combined with the sustained release effect of molluscicide amine ethanolamine salt microcapsules, it has the effect of continuously luring and killing male golden apple snails.

[0030] 4. Compared with the commercially available separate molluscicide ethanolamine salt water dispersible granules or other pesticide preparations directly containing molluscicide ethanolamine salt original drug, the pesticide preparation containing molluscicide ethanolamine salt provided by the present invention, the molluscicide ethanolamine salt is present in the preparation particles in the form of being encapsulated in microcapsules, and the microcapsules are in turn encapsulated by solid powder, which can not only mask the inherent odor of the molluscicide ethanolamine salt and avoid the phytotoxicity to sensitive crops; but also improve the mixing compatibility of the molluscicide ethanolamine salt with other substances, and reduce the difficulty of mixing with other substances; and can also improve the physical stability of the pesticide preparation containing molluscicide ethanolamine salt during storage, and can increase the effective period of the molluscicide ethanolamine salt; it can well ensure the synergistic effect of various substances in the preparation, improve the prevention and control efficiency, prolong the effective period, and slow down the occurrence of drug resistance. DETAILED DESCRIPTION

[0031] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0032] Example 1

[0033] This embodiment provides a microcapsule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0034] 0.5g of molasses-killing amine ethanolamine salt, 0.3g of 4-hydroxyphenylacetic acid, 20mL of deionized water and 20mL of anhydrous ethanol were mixed, and the pH value was adjusted to 7.4 with 0.1mol / L NaOH solution as the aqueous phase, and stirred. 16g of triolein and 3g of Span-85 were mixed to form the oil phase. The aqueous phase was added dropwise to the oil phase and ultrasonically emulsified at room temperature for 30min. Then, 0.1mL of butyl cyanoacrylate monomer and 0.1mL of 2-dodecyl acrylate monomer were added dropwise to the emulsion under stirring, and after 2h polymerization, centrifuged to obtain molasses-killing amine ethanolamine salt microcapsules.

[0035] Example 2

[0036] This embodiment provides a microcapsule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0037] 1g of molasses-killing amine ethanolamine salt, 0.6g of 4-hydroxyphenylacetic acid, 40mL of deionized water and 40mL of anhydrous ethanol were mixed, and the pH value was adjusted to 7.4 with 0.1mol / L NaOH solution, as the aqueous phase, and stirred. 32g of triolein and 6g of Span-85 were mixed to form the oil phase. The aqueous phase was added dropwise to the oil phase and ultrasonically emulsified for 30min at room temperature. Then, 0.2mL of butyl cyanoacrylate monomer and 0.2mL of 2-dodecyl acrylate monomer were added dropwise to the emulsion under stirring, and after 2h polymerization, centrifuged to obtain molasses-killing amine ethanolamine salt microcapsules.

[0038] Example 3

[0039] This embodiment provides a microcapsule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0040] 5g of molasses-killing amine ethanolamine salt, 3g of 4-hydroxyphenylacetic acid, 200mL of deionized water and 200mL of anhydrous ethanol were mixed, and the pH value was adjusted to 7.4 with 0.1mol / L NaOH solution, as the aqueous phase, and stirred. 160g of triolein and 30g of Span-85 were mixed to form the oil phase. The aqueous phase was added dropwise to the oil phase and ultrasonically emulsified for 30min at room temperature. Then, 1mL of butyl cyanoacrylate monomer and 1mL of 2-lauryl acrylate monomer were added dropwise to the above-mentioned emulsion under stirring, and after 2h polymerization, centrifuged to obtain molasses-killing amine ethanolamine salt microcapsules.

[0041] Comparative Example 1

[0042] This embodiment provides a microcapsule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0043] Compared with Example 1, on the basis of Example 1, 0.1 mL of 2-dodecyl acrylate was removed, and the remaining reagents and preparation steps were the same as those in Example 1.

[0044] Comparative Example 2

[0045] This embodiment provides a microcapsule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0046] Compared with Example 1, on the basis of Example 1, 0.3 g of 4-hydroxyphenylacetic acid was removed, and the remaining reagents and preparation steps were the same as those in Example 1.

[0047] Example 4

[0048] This embodiment provides a sustained-release water-dispersible granule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0049] 200.0g of SP-27001 dispersant (purchased from Jiangsu Qingyu Chemical Technology Co., Ltd.), 250.0g of lignin sulfonate, 10.0g of sodium dodecyl sulfate, 5g of citric acid, 35g of white carbon black and 500g of calcined kaolin were mixed evenly, and ultrafinely ground into a solid powder with 99% passing 400 mesh, and set aside.

[0050] 87.5 g of the molluscicide ethanolamine salt microcapsules prepared in Example 1 were evenly mixed with 938.8 g of the solid powder obtained in the above step, and then 200 mL of a 0.5% polyvinyl alcohol aqueous solution (polyvinyl alcohol has a molecular weight of 47,000 and is purchased from Shanghai MacLean Biochemical Technology Co., Ltd.) was added. The material was sent to an extrusion granulator for granulation, placed in a vacuum drying oven at 60° C. for 12 h, and sieved through 600 mesh to obtain molluscicide ethanolamine salt sustained-release water-dispersible granules.

[0051] Example 5

[0052] This embodiment provides a sustained-release water-dispersible granule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0053] 400.0 g of SP-27001 dispersant (purchased from Jiangsu Qingyu Chemical Technology Co., Ltd.), 500.0 g of lignin sulfonate, 20.0 g of sodium dodecyl sulfate, 10 g of citric acid, 70 g of white carbon black and 1000 g of calcined kaolin were mixed evenly, and ultrafinely ground into a solid powder with 99.5% passing 500 mesh, and set aside.

[0054] 175 g of the molluscicide ethanolamine salt microcapsules prepared in Example 2 were evenly mixed with 1877.6 g of the solid powder obtained in the above step, and then 400 mL of a 2% polyvinyl alcohol aqueous solution (polyvinyl alcohol having a molecular weight of 47,000, purchased from Shanghai MacLean Biochemical Technology Co., Ltd.) was added. The material was fed into an extrusion granulator for granulation, dried in a vacuum drying oven at 60° C. for 12 h, and sieved through 600 mesh to obtain molluscicide ethanolamine salt sustained-release water-dispersible granules.

[0055] Example 6

[0056] This embodiment provides a sustained-release water-dispersible granule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0057] 600.0g of SP-27001 dispersant (purchased from Jiangsu Qingyu Chemical Technology Co., Ltd.), 750.0g of lignin sulfonate, 30.0g of sodium dodecyl sulfate, 15g of citric acid, 105g of white carbon black and 1500g of calcined kaolin were mixed evenly, and ultrafinely ground into a solid powder with 99.9% passing 600 mesh, and set aside.

[0058] 437.5 g of the molluscicide ethanolamine salt microcapsules prepared in step Example 3 were mixed evenly with 4694 g of the solid powder obtained in the above step, and then 1000 mL of a 5% polyvinyl alcohol aqueous solution (polyvinyl alcohol has a molecular weight of 47,000 and is purchased from Shanghai MacLean Biochemical Technology Co., Ltd.) was added. The material was sent to an extrusion granulator for granulation, placed in a vacuum drying oven at 60° C. for 12 h, and sieved through 600 mesh to obtain molluscicide ethanolamine salt sustained-release water-dispersible granules.

[0059] Comparative Example 3

[0060] This embodiment provides a sustained-release water-dispersible granule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0061] Compared with Example 3, on the basis of Example 3, the molluscicidal ethanolamine salt microcapsules prepared in Example 1 were replaced by the molluscicidal ethanolamine salt microcapsules prepared in Comparative Example 1, and the remaining raw materials and preparation steps were the same as those in Example 3.

[0062] Comparative Example 4

[0063] This embodiment provides a sustained-release water-dispersible granule of molluscicide ethanolamine salt, and the preparation steps are as follows:

[0064] Compared with Example 3, on the basis of Example 3, the molluscicidal ethanolamine salt microcapsules prepared in Example 1 were replaced by the molluscicidal ethanolamine salt microcapsules prepared in Comparative Example 2, and the remaining raw materials and preparation steps were the same as those in Example 3.

[0065] The performance of the molluscicide ethanolamine salt slow-release water-dispersible granules prepared in Examples 4-6 and Comparative Examples 3-4 was tested. The molluscicide ethanolamine salt slow-release water-dispersible granules prepared in the above Examples and Comparative Examples were used to conduct field efficacy experiments on Pomacea canaliculata in rice fields. The number of live and dead snails in each area was checked on the 1st, 5th, and 14th days after the drug was applied, and the mortality rate of Pomacea canaliculata was calculated. Mortality rate = (number of live snails before treatment - number of live snails after treatment) / number of live snails before treatment × 100%.

[0066] Among them, the rainfall on rainy days is 5.0 mm within 24 hours. The results are shown in Table 1:

[0067] Table 1

[0068]

[0069] As can be seen from Table 1, after 1, 3, 7, and 14 days of application, the mortality rate of Pomacea canaliculata gradually increased and reached the maximum on the 7th day, and decreased after the 14th day, indicating that the sustained-release effect of the molluscicide amine ethanolamine salt sustained-release water-dispersible granules is very good and can significantly reduce the number of applications. Compared with other embodiments, it can be seen that 4-hydroxyphenylacetic acid, as a sex pheromone of male Pomacea canaliculata, significantly improves the killing rate of Pomacea canaliculata. Compared with the embodiments, it can be seen that the use of acrylic acid monomers with hydrophobic groups in Comparative Example 3 can greatly improve the ability of the molluscicide amine ethanolamine salt sustained-release water-dispersible granules to resist rain erosion.

[0070] It should be noted that, in this article, relational terms such as first and second, etc. are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the terms "include", "comprise" or any other variants thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device.

[0071] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A process for preparing a sustained-release water-dispersible granule of molluscicide ethanolamine salt, characterized in that: The operation steps are: Step (1): preparation of molluscicide ethanolamine salt microcapsules; Step (2): preparing solid powder; Step (3): Preparation of sustained-release water-dispersible granules of molluscicide ethanolamine salt.

2. The preparation process of the sustained-release water-dispersible granules of molluscicide ethanolamine salt according to claim 1, characterized in that: The molluscicide ethanolamine salt microcapsules include the following preparation steps: The method comprises the following steps: mixing molluscicidal ethanolamine salt, 4-hydroxyphenylacetic acid, deionized water and anhydrous ethanol, adjusting the pH thereof to 7.4, using the mixture as a water phase, and stirring; mixing triolein and Span-85 to form an oil phase; dropping the water phase into the oil phase, and ultrasonically emulsifying the mixture at room temperature; stirring, dropping butyl cyanoacrylate and 2-dodecyl acrylate, polymerizing the mixture, and centrifuging the mixture to obtain molluscicidal ethanolamine salt microcapsules.

3. The preparation process of the sustained-release water-dispersible granules of molluscicide ethanolamine salt according to claim 1, characterized in that: The dosage ratio of the molluscicide ethanolamine salt, 4-hydroxyphenylacetic acid, deionized water, anhydrous ethanol, triolein, Span-85, butyl cyanoacrylate and 2-dodecyl acrylate is 0.5g:0.3g:20mL:20mL:16g:3g:0.1mL:0.1mL.

4. The preparation process of the sustained-release water-dispersible granules of molluscicide ethanolamine salt according to claim 1, characterized in that: The preparation of the solid powder comprises the following preparation steps: SP-27001 dispersant, lignin sulfonate, sodium dodecyl sulfate, citric acid, white carbon black and calcined kaolin are mixed, ultrafinely ground and sieved to obtain a solid powder.

5. The preparation process of the sustained-release water-dispersible granules of molluscicide ethanolamine salt according to claim 1, characterized in that: The molluscicide ethanolamine salt sustained-release water-dispersible granules include the following preparation steps: The molluscicide ethanolamine salt microcapsules obtained in step (1) are mixed evenly with the solid powder obtained in step (2), and then a polyvinyl alcohol aqueous solution is added and mixed evenly. The material is sent to an extrusion granulator for granulation, drying and sieving to obtain molluscicide ethanolamine salt sustained-release water-dispersible granules.

6. The preparation process of the sustained-release water-dispersible granules of molluscicide ethanolamine salt according to claim 4, characterized in that: The mass ratio of the SP-27001 dispersant, lignin sulfonate, sodium dodecyl sulfate, citric acid, white carbon black and calcined kaolin is 200:250:10:5:35:

500.

7. The process for preparing the sustained-release water-dispersible granules of molluscicide ethanolamine salt according to claim 5, characterized in that: The dosage ratio of the molluscicide ethanolamine salt microcapsules, the solid powder and the polyvinyl alcohol aqueous solution is 87.5g:938.8g:200mL.

8. A sustained-release water-dispersible granule of molluscicide ethanolamine salt, characterized in that: The invention is prepared by the preparation process according to any one of claims 1 to 7.

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