Pesticide-carrying capsule for pesticide and preparation method of pesticide-carrying capsule

Abstract

The invention relates to the technical field of pesticide preparations, in particular to a pesticide-loaded capsule and a preparation method thereof. The drug-loaded capsule is prepared by the following method: (1) emulsifying a water phase containing polyvinyl alcohol and an emulsifier and an oil phase containing a drug to obtain an oil-in-water emulsion; (2) carrying out cross-linking reaction on the oil-in-water emulsion and a boron cross-linking agent to obtain a drug-loaded capsule; wherein relative to 1 g of polyvinyl alcohol, the dosage of the boron crosslinking agent is 0.01-2 g. The preparation method disclosed by the invention is simple, and the obtained drug-loaded capsule is high in encapsulation efficiency and long in slow release period, can be accurately adapted to a slightly acidic rhizosphere environment to trigger release, and has excellent ecological compatibility to the environment and crops.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticide preparations, and in particular to a pesticide-carrying capsule and a preparation method thereof. Background Art

[0002] Current pesticide formulations suffer from low utilization rates due to factors such as non-targeted release and susceptibility to rainwater erosion, and residual pesticides can easily cause environmental pollution. Taking thiazolyl as an example, although it has highly effective nematicidal activity, its properties lead to rapid degradation in soil, requiring frequent application and posing the risk of pesticide damage. Existing microencapsulation technologies have low encapsulation efficiency, making it difficult to achieve stable sustained release. Furthermore, while physical control methods such as high-temperature suffocation can kill nematodes, they are complex and damage soil ecology. Therefore, to address these issues, developing a new pesticide formulation that breaks through the pesticide encapsulation bottleneck and avoids the toxic risks of traditional processes has become an urgent issue. Summary of the Invention

[0003] The present invention aims to overcome the problems of the prior art by providing a pesticide-loaded capsule and a method for preparing the same. The capsule has a high encapsulation efficiency, a long sustained-release period, can precisely adapt to the slightly acidic rhizosphere environment to trigger release, and exhibits excellent ecological compatibility with the environment and crops.

[0004] In order to achieve the above object, the present invention provides a method for preparing a drug-loaded capsule, the method comprising:

[0005] (1) emulsifying an aqueous phase containing polyvinyl alcohol and an emulsifier with an oil phase containing a drug to obtain an oil-in-water emulsion;

[0006] (2) cross-linking the oil-in-water emulsion with a boron cross-linking agent to obtain a drug-loaded capsule;

[0007] Wherein, relative to 1g of the polyvinyl alcohol, the amount of the boron cross-linking agent is 0.01-2g.

[0008] The second aspect of the present invention provides a drug-loaded capsule prepared by the above method.

[0009] A third aspect of the present invention provides a use of the above-mentioned drug-loaded capsule in a pesticide formulation.

[0010] The present invention is constructed through the interfacial cross-linking reaction of a boron cross-linking agent and polyvinyl alcohol, and adopts an "emulsification first-then curing" process to encapsulate water-soluble drugs in a hydrophobic cross-linked network, thereby achieving synergistic enhancement of targeted sustained release and anti-leaching functions.

[0011] The drug-loaded capsules obtained by the present invention have the following advantages:

[0012] (1) Green process and safety: It adopts an environmentally friendly dynamic boron ester bond cross-linking system to avoid soil pollution risks, has no inhibitory effect on crop germination, and has excellent ecological compatibility.

[0013] (2) Intelligent release mechanism: Through the pH response characteristics of the boron ester bond, it accurately adapts to the rhizosphere gastric acid environment to trigger release, avoids non-targeted losses, and significantly improves pesticide utilization.

[0014] (3) Long-term sustained release and stability: The three-dimensional cross-linked network combined with the large-particle hydrophobic structure achieves a sustained release period of ≥30 days, and has outstanding resistance to rain erosion, with a duration of effect 3-6 times that of conventional preparations.

[0015] (4) High encapsulation and universality: Based on the optimization of the water-in-oil emulsion interface, it breaks through the bottleneck of pesticide encapsulation technology. The encapsulation rate is significantly higher than that of traditional microencapsulation technology and is suitable for a variety of pesticide loading.

[0016] (5) Potential for low-cost industrialization: Raw materials are cheap and readily available, and the process does not require complex equipment or high-temperature and high-pressure conditions. The two-step emulsification-cross-linking method can be used for large-scale production, which combines technical barriers with commercial feasibility. DETAILED DESCRIPTION

[0017] The endpoints of the ranges and any values disclosed herein are not limited to the precise ranges or values, and these ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and individual point values, and the individual point values can be combined with each other to obtain one or more new numerical ranges, which should be considered to be specifically disclosed herein.

[0018] One aspect of the present invention provides a method for preparing a drug-loaded capsule, the method comprising:

[0019] (1) emulsifying an aqueous phase containing polyvinyl alcohol and an emulsifier with an oil phase containing a drug to obtain an oil-in-water emulsion;

[0020] (2) cross-linking the oil-in-water emulsion with a boron cross-linking agent to obtain a drug-loaded capsule;

[0021] Wherein, relative to 1g of the polyvinyl alcohol, the amount of the boron cross-linking agent is 0.01-2g.

[0022] According to the present invention, polyvinyl alcohol has good biocompatibility, stability and hydroxyl activity. The boron cross-linker can form a three-dimensional network structure with the hydroxyl group of polyvinyl alcohol through a dynamic boron ester bond, thereby achieving high encapsulation of the drug. At the same time, through the pH response characteristics of the boron ester bond breaking under an environment of pH 5-6.5, the drug can be triggered to release in the slightly acidic environment of the rhizosphere to improve the utilization rate of the pesticide.

[0023] According to the present invention, in order to achieve a better cross-linking effect and improve the various properties of the drug-loaded capsule, the selection and dosage of the boron cross-linking agent can be adjusted. Preferably, relative to 1g of the polyvinyl alcohol, the dosage of the boron cross-linking agent is 0.2-1g, for example, it can be 0.25g, 0.5g, 0.83g, and 1g and any range between the values.

[0024] Preferably, the boron crosslinking agent is selected from one or more of 1,4-phenylenediboronic acid, diboric acid, pyridine-3,5-diyldiboric acid, naphthalene-2,6-diyldiboric acid, anthracene-9,10-diboric acid, 2-methyl-1,4-terephthalenediboric acid, benzofuran-2,5-diboric acid, 4,4'-oxybis(1,4-phenylene)diboric acid, 4,4'-biphenylenediboric acid, 2,5-thiophene diboronic acid, 1,2-phenylenediboric acid and 1,4-naphthalenediboric acid, preferably 1,4-phenylenediboric acid and / or 1,2-phenylenediboric acid.

[0025] According to the present invention, in order to enable the drug-loaded capsules to achieve a longer sustained-release period and improve their resistance to rain erosion, preferably, the particle size of the drug-loaded capsules is 0.5-4 mm, preferably 1-3 mm, for example, it can be 1 mm, 1.5 mm, 2 mm and 3 mm and any range between the values.

[0026] According to the present invention, the drug can be selected from a wide range. Generally, the drug-loaded capsule of the present invention is more suitable for soil-applied pesticides. In order to achieve better effects, preferably, the drug is selected from one or more of thiazolyl, imidacloprid, abamectin, carbendazim, thiophanate-methyl, azoxystrobin, acetochlor, trifluralin, propargite and spirotetramat, preferably one or more of thiazolyl, azoxystrobin and trifluralin.

[0027] According to the present invention, in order to better perform the emulsification process and obtain an oil-in-water emulsion with better properties, the selection and dosage of the emulsifier can be adjusted. Preferably, the emulsifier is selected from one or more of nonionic emulsifiers, anionic emulsifiers, cationic emulsifiers and zwitterionic emulsifiers, preferably one or more of nonionic emulsifiers, more preferably Tween-20 and / or Tween-80;

[0028] Preferably, relative to 1g of the polyvinyl alcohol, the amount of the emulsifier is 0.05-1.5g, preferably 0.1-1g, for example, it can be 0.16g, 0.5g, 0.8g, 1g and any range therebetween.

[0029] According to the present invention, in order to prepare a better oil-in-water emulsion, facilitate the cross-linking reaction, and ultimately obtain drug-loaded capsules with excellent performance, preferably, the amount of water in the aqueous phase relative to 1g of the polyvinyl alcohol is 1-50mL, preferably 5-40mL, for example, it can be 6.6mL, 10mL, 17mL, 25mL, 33mL and 40mL and the range between any values ​​and any values therebetween.

[0030] According to the present invention, in order to better emulsify the oil phase with the aqueous phase, preferably, the amount of the drug is 0.2-5g relative to 1g of the polyvinyl alcohol, preferably 0.5-3.5g, for example, it can be 0.66g, 1g, 1.66g, 2.5g and 3.3g and the range between any values thereof.

[0031] Preferably, the solvent of the oil phase is selected from one or more of xylene, cyclohexane, toluene, cyclohexanone and modified vegetable oil, preferably xylene and / or cyclohexane.

[0032] Preferably, relative to 1g of the polyvinyl alcohol, the amount of the solvent in the oil phase is 0.5-8g, preferably 1-5g, for example, it can be 1g, 1.5g, 2.5g, 3.75g and 5g and any range therebetween.

[0033] According to the present invention, in order to achieve better cross-linking effect, preferably, the molecular weight of the polyvinyl alcohol is 9000-150000 g / mol, preferably 25000-50000 g / mol, for example, it can be 25000 g / mol, 30000 g / mol, 40000 g / mol and 50000 g / mol and any value thereof.

[0034] According to the present invention, in order to facilitate the cross-linking reaction, preferably, the polyvinyl alcohol is provided in the form of an aqueous solution, and the concentration of the polyvinyl alcohol aqueous solution is 1-20wt%, preferably 2-15wt%, for example, it can be 3wt%, 6wt%, 10wt% and 15wt% and the range between any values.

[0035] According to the present invention, in order to obtain drug-loaded capsules with better performance, preferably, the boron crosslinking agent is provided in the form of a solution, and the concentration of the boron crosslinking agent solution is 0.2-20wt%, preferably 3-10wt%, for example, it can be 4wt%, 5wt%, 6wt%, 8wt% and 10wt% and the range between any values.

[0036] Preferably, when the boron cross-linking agent is provided in the form of a solution, the solvent for dissolving the boron cross-linking agent is selected from one or more of methanol, ethanol, and dimethyl sulfoxide, preferably methanol and / or dimethyl sulfoxide.

[0037] According to the present invention, in order to obtain an oil-in-water emulsion that meets the requirements, preferably, the shear rate of the emulsification treatment is 5000-25000 rpm, preferably 10000-20000 rpm, for example, it can be 10000 rpm, 15000 rpm, 18000 rpm and 20000 rpm and any range therebetween.

[0038] Preferably, the emulsification treatment time is 2-20 min, preferably 5-10 min, for example, it can be 5 min, 7 min, 8 min, 10 min, and any range therebetween.

[0039] According to the present invention, in order to obtain drug-loaded capsules with better properties and performance, preferably, the cross-linking reaction time is 5-30 min, preferably 10-20 min, for example, it can be 10 min, 12 min, 15 min and 20 min and any range therebetween.

[0040] According to the present invention, after the cross-linking reaction is completed, the resulting reaction solution can be post-treated. The post-treatment method can be selected from a wide range. Preferably, the post-treatment method includes filtering and washing the reaction solution, and vacuum drying to obtain the drug-loaded capsule. The washing solvent can be, for example, water, methanol, etc.; the vacuum drying temperature can be, for example, 30-60°C.

[0041] The second aspect of the present invention provides a drug-loaded capsule prepared by the above method.

[0042] A third aspect of the present invention provides a use of the above-mentioned drug-loaded capsule in a pesticide formulation.

[0043] This invention utilizes an interfacial cross-linking reaction between a boron-based cross-linker and polyvinyl alcohol, employing an "emulsification followed by curing" process to encapsulate water-soluble drugs within a hydrophobic cross-linked network, achieving synergistic effects of targeted sustained release and anti-leaching properties. The resulting drug-loaded capsules have a high encapsulation efficiency, a long sustained-release period, and can precisely adapt to the slightly acidic rhizosphere environment to trigger release. They also exhibit excellent ecological compatibility with the environment and crops.

[0044] The present invention will be described in detail below through examples.

[0045] In the following examples, the apparatus used are all conventional experimental apparatuses in the art, the experimental procedures adopted are all conventional procedures in the art, and the raw materials and reagents used are all commercially available. Among them, all polyvinyl alcohol was purchased from Shanghai MacLean Biochemical Technology Co., Ltd.

[0046] Example 1

[0047] (1) Disperse 0.5 g of Tween-80 in 20 mL of water, add 20 g of a 10 wt% polyvinyl alcohol aqueous solution (the amount of polyvinyl alcohol used is 2 g, and the molecular weight is 27,000 g / mol), and stir to dissolve to obtain an aqueous phase.

[0048] (2) Disperse 2 g of thiazole phosphine in 3 g of xylene and dissolve to obtain an oil phase.

[0049] (3) The oil phase was slowly added to the water phase and emulsified at a shear rate of 20,000 rpm for 8 min to obtain an oil-in-water emulsion.

[0050] (4) The oil-in-water emulsion was slowly added to 20 g of a 5 wt% 1,4-phenylenediboronic acid methanol solution (the amount of 1,4-phenylenediboronic acid was 1 g), and the cross-linking reaction was carried out for 20 min. After the reaction was completed, the reaction solution was filtered and washed with water and methanol, and then vacuum-dried at 40°C to obtain drug-loaded capsules with a particle size of 1.5 mm.

[0051] Example 2

[0052] The method of Example 1 is different in that, in step (1), the 10 wt % polyvinyl alcohol aqueous solution is replaced by a 4 wt % polyvinyl alcohol aqueous solution.

[0053] In step (4), the 5 wt % 1,4-phenylenediboric acid methanol solution is replaced with a 1 wt % 1,4-phenylenediboric acid methanol solution.

[0054] Example 3

[0055] The method of Example 1 is different in that, in step (1), the 10 wt % polyvinyl alcohol aqueous solution is replaced by a 3 wt % polyvinyl alcohol aqueous solution.

[0056] In step (4), the 5 wt % 1,4-phenylenediboric acid methanol solution is replaced with a 2 wt % 1,4-phenylenediboric acid methanol solution.

[0057] Example 4

[0058] The method of Example 1 is different in that in step (1), the 10 wt % polyvinyl alcohol aqueous solution is replaced by a 6 wt % polyvinyl alcohol aqueous solution (the amount of polyvinyl alcohol used is 1.2 g, and the molecular weight is 47000 g / mol).

[0059] In step (4), the 5 wt % 1,4-phenylenediboronic acid methanol solution is replaced with a 5 wt % 1,4-phenylenediboronic acid dimethyl sulfoxide solution.

[0060] Example 5

[0061] The method of Example 1 is different in that, in step (1), the 10 wt % polyvinyl alcohol aqueous solution is replaced by a 15 wt % polyvinyl alcohol aqueous solution.

[0062] In step (4), the 5 wt % 1,4-phenylenediboric acid methanol solution is replaced with a 15 wt % 1,4-phenylenediboric acid methanol solution.

[0063] Example 6

[0064] The method of Example 1 is different in that in step (1), the amount of Tween-80 used is 0.1 g.

[0065] Example 7

[0066] The method of Example 1 is different in that in step (1), the amount of Tween-80 used is 3 g.

[0067] Example 8

[0068] The method of Example 1 is different in that, in step (3), the shear rate is 5000 rpm.

[0069] Example 9

[0070] The method of Example 1 is different in that, in step (3), the shear rate is 25000 rpm.

[0071] Example 10

[0072] The method of Example 1 is different in that, in step (4), the 5 wt % 1,4-phenylenediboric acid methanol solution is replaced by a 5 wt % naphthalene-2,6-diyldiboric acid methanol solution.

[0073] Comparative Example 1

[0074] The method of Example 1 is different in that, in step (4), the amount of 5 wt% 1,4-phenylenediboronic acid methanol solution used is 0.2 g (the amount of 1,4-phenylenediboronic acid is 0.01 g).

[0075] Comparative Example 2

[0076] The method of Example 1 is different in that, in step (4), the amount of 5 wt% 1,4-phenylenediboronic acid methanol solution used is 100 g (the amount of 1,4-phenylenediboronic acid is 5 g).

[0077] Comparative Example 3

[0078] The method of Example 1 is different in that, in step (4), the 5 wt % 1,4-phenylenediboronic acid methanol solution is replaced by a 5 wt % glutaraldehyde solution.

[0079] Test Example 1

[0080] Entrapment efficiency: The entrapment efficiency of the drug-loaded capsules was determined by high performance liquid chromatography (standard curve method).

[0081] Sustained-release performance: The drug-loaded capsules were placed in a phosphate buffer solution with a pH of 6, and the cumulative drug release over 72 hours was determined using the cumulative release rate calculation formula;

[0082] Cumulative release rate calculation formula: Wherein, Er is the cumulative release amount of thiazolylphosphatidylcholine in the drug-loaded capsule (%); V e is the sampling volume; C n is the concentration of thiazolyl in the release solution at the nth sampling (mg / mL); V0 is the total volume of the release medium; M p is the total mass of thiazolyl in the drug-loaded capsule (mg).

[0083] Leaching resistance: simulated rainfall (100 mm / h) was applied to the drug-loaded capsules for 1 hour, and the drug leaching amount was determined by HPLC using the cumulative leaching rate calculation formula.

[0084] The calculation formula of cumulative leaching rate is: Wherein, Lr is the cumulative leaching amount of pesticide in the drug-loaded capsule (%); m i is the mass of pesticide in the i-th water sample (mg); M p is the total mass of pesticide in the drug-loaded capsule (mg).

[0085] The test results are shown in Table 1.

[0086] Table 1

[0087]

[0088]

[0089] As can be seen from Table 1, the various performances of Examples 1-10 using the technical solution of the present invention are better than those of Comparative Examples 1-3.

[0090] Test Example 2

[0091] The drug-loaded capsules prepared in Examples 2-5 were tested.

[0092] Cross-linking density: The swelling rate of the drug-loaded capsules was tested by the swelling method to reflect the cross-linking density.

[0093] The test results are shown in Table 2.

[0094] Table 2

[0095]

[0096] It can be seen from Table 2 that Examples 2-4 have relatively low swelling ratios, with Example 4 having a swelling ratio as low as 1.8%, indicating good cross-linking density.

[0097] Test Example 3

[0098] The drug-loaded capsules prepared in Example 1 were placed in phosphate buffer solutions with pH values of 5, 6, and 7, respectively, and their drug release over 72 hours was measured by high performance liquid chromatography.

[0099] The results showed that at a pH of 5, the drug-loaded capsules released 90% of the drug by weight over 48 hours, with complete release within 72 hours. At a pH of 6, the drug-loaded capsules released 20.2% of the drug by weight over 72 hours. At a pH of 7, the drug-loaded capsules released less than 15% of the drug by weight over 72 hours.

[0100] Test Example 4

[0101] Field efficacy was verified in greenhouses where tomato root-knot nematode infections were detected. The drug-loaded capsules prepared in Example 1 and conventional granules were applied to determine their efficacy and ecological differences. Results showed that the drug-loaded capsules prepared in Example 1 achieved a 92.3% efficacy 60 days after application, while the conventional granules achieved a 70.5% efficacy. The tomato seed germination rate after application of the drug-loaded capsules prepared in Example 1 was 96.7%, which was statistically insignificant compared to the blank control group (97.2%).

[0102] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, various simple variations of the technical solution of the present invention may be made, including combining the various technical features in any other appropriate manner. These simple variations and combinations should also be regarded as disclosed in the present invention and fall within the scope of protection of the present invention.

Claims

1. A method for preparing a drug-loaded capsule, characterized in that: The method includes: (1) emulsifying an aqueous phase containing polyvinyl alcohol and an emulsifier with an oil phase containing a drug to obtain an oil-in-water emulsion; (2) cross-linking the oil-in-water emulsion with a boron cross-linking agent to obtain a drug-loaded capsule; Wherein, relative to 1g of the polyvinyl alcohol, the amount of the boron cross-linking agent is 0.01-2g.

2. The method according to claim 1, wherein The amount of the boron crosslinking agent used is 0.2-1 g relative to 1 g of the polyvinyl alcohol; and / or, the boron crosslinking agent is selected from one or more of 1,4-phenylenediboronic acid, diboric acid, pyridine-3,5-diyldiboric acid, naphthalene-2,6-diyldiboric acid, anthracene-9,10-diboric acid, 2-methyl-1,4-terephthalenediboric acid, benzofuran-2,5-diboric acid, 4,4'-oxybis(1,4-phenylene)diboric acid, 4,4'-biphenylenediboric acid, 2,5-thiophene diboronic acid, 1,2-phenylenediboric acid and 1,4-naphthalenediboric acid, preferably 1,4-phenylenediboric acid and / or 1,2-phenylenediboric acid; and / or, the particle size of the drug-loaded capsule is 0.5-4 mm, preferably 1-3 mm; And / or, the drug is selected from one or more of thiazolyl, imidacloprid, avermectin, carbendazim, thiophanate-methyl, azoxystrobin, acetochlor, trifluralin, propargite and spirotetramat, preferably one or more of thiazolyl, azoxystrobin and trifluralin.

3. The method according to claim 1 or 2, wherein: The emulsifier is selected from one or more of nonionic emulsifiers, anionic emulsifiers, cationic emulsifiers and zwitterionic emulsifiers, preferably one or more nonionic emulsifiers, more preferably Tween-20 and / or Tween-80; and / or, relative to 1g of the polyvinyl alcohol, the amount of the emulsifier is 0.05-1.5g, preferably 0.1-1g; And / or, relative to 1 g of the polyvinyl alcohol, the amount of water in the aqueous phase is 1-50 mL, preferably 5-40 mL.

4. The method according to any one of claims 1 to 3, wherein: Relative to 1g of the polyvinyl alcohol, the dosage of the drug is 0.2-5g, preferably 0.5-3.5g; and / or, the solvent of the oil phase is selected from one or more of xylene, cyclohexane, toluene, cyclohexanone and modified vegetable oil, preferably xylene and / or cyclohexane; And / or, relative to 1g of the polyvinyl alcohol, the amount of the solvent in the oil phase is 0.5-8g, preferably 1-5g.

5. The method according to any one of claims 1 to 4, wherein: The molecular weight of the polyvinyl alcohol is 9,000-150,000 g / mol, preferably 25,000-50,000 g / mol.

6. The method according to any one of claims 1 to 5, wherein: The polyvinyl alcohol is provided in the form of an aqueous solution, and the concentration of the polyvinyl alcohol aqueous solution is 1-20 wt %, preferably 2-15 wt %.

7. The method according to any one of claims 1 to 6, wherein: The boron cross-linking agent is provided in the form of a solution, and the concentration of the boron cross-linking agent solution is 0.2-20 wt %, preferably 3-10 wt %; Preferably, when the boron cross-linking agent is provided in the form of a solution, the solvent for dissolving the boron cross-linking agent is selected from one or more of methanol, ethanol, and dimethyl sulfoxide, preferably methanol and / or dimethyl sulfoxide.

8. The method according to any one of claims 1 to 7, wherein: The shear rate of the emulsification treatment is 5000-25000 rpm, preferably 10000-20000 rpm; And / or, the emulsification treatment time is 2-20 min, preferably 5-10 min; And / or, the cross-linking reaction time is 5-30 min, preferably 10-20 min.

9. The drug-loaded capsule prepared by the method according to any one of claims 1 to 8.

10. Use of the drug-loaded capsule according to claim 9 in pesticide preparations.

Images