Microencapsulation of insecticides

Abstract

An organic / oil mixture for use in an emulsion to form microcapsules of the present disclosure. The organic / oil mixture includes abamectin; a non-polar solvent having a Hansen solubility parameter with a polarity (P) value of 0 to 3; a polar solvent of Formula I: wherein R1 is a C1 to C15 alkyl; R2 is H or a C1 to C8 alkyl; R3 is a C1 to C15 alkylene; and R4 is a C1 to C15 alkyl, wherein the sum of carbons in R1, R2, R4 alkyl, and R3 alkylene is 8 to 30; and 2.5 to 20 weight percent of an isocyanate, wherein each weight percent is based on the total weight of the organic / oil mixture, and the sum of the weight percent of the abamectin, the non-polar solvent, the polar solvent, and the isocyanate totals 100 weight percent.

Description

Technical Field

[0001] This disclosure relates to microencapsulation, and more specifically to the microencapsulation of insecticides. Background Technology

[0002] Abamectin is widely used to control pests and mites in various crops, fruits, vegetables, and ornamental crops. However, abamectin has undesirable properties: firstly, it is highly photosensitized and easily oxidized; secondly, it is toxic to humans and animals.

[0003] Attempts to address photosensitivity and oxidation issues have taken different approaches. For example, avermectin is sold as an emulsion concentrate (EC) (e.g., at a concentration of 18 g / L), which includes antioxidants and / or UV shielding agents that help minimize the photodegradation of avermectin. Alternatively, the photosensitivity problem of avermectin has been addressed by microencapsulating avermectin using an emulsion process. The microencapsulation emulsification process begins by emulsifying an oil phase containing avermectin and one or more hydrophobic solvents in an aqueous phase containing one or more surfactants and one or more dispersants. Microcapsules are then formed around oil droplets in the emulsion through monomer polymerization.

[0004] However, a key aspect of the first step in microencapsulation involves preparing an active solution using a solvent with good compatibility and solubility with the suspension system to achieve the target activity loading level. The suspension system also needs to be well-hydrophobic to facilitate microcapsule formation. However, avermectin has very low solubility in typical hydrophobic aromatic agricultural solvents. For example, it is difficult to achieve even a loading level of 1% by weight of avermectin in microcapsules.

[0005] Another challenge in microencapsulating avermectin is the chemical process used in the microencapsulation. Typical microencapsulation processes utilize interfacial polymerization based on polyurea / polyurethane chemistry. This process uses isocyanate monomers to create the microcapsule walls. However, avermectin possesses hydroxyl groups (one secondary hydroxyl and two tertiary hydroxyl groups), as shown in Formula I. These hydroxyl groups can react with the isocyanate monomers, leading to the degradation of avermectin during microcapsule formation.

[0006]

[0007] Therefore, there is a need in this field to improve the microencapsulation of avermectin. Summary of the Invention

[0008] This disclosure provides improvements in the microencapsulation of avermectin. In particular, it provides an active solution with a solvent exhibiting good avermectin solubility, achieving a target avermectin loading level (3 to 5% by weight), and good hydrophobicity to facilitate capsule formation while minimizing avermectin degradation during the capsule formation process. Specifically, it has been surprisingly found that the use of a specific polar solvent in combination with a nonpolar solvent in an organic / oil mixture (discussed herein) produces microcapsules containing a weight percentage of avermectin comparable to the weight percentage of avermectin in the organic / oil mixture used to form the microcapsules. In other words, the surprisingly close weight percentage of avermectin in the microcapsules to the weight percentage of avermectin in the organic / oil mixture used to form the microcapsules indicates that avermectin is unexpectedly well protected during the encapsulation reaction.

[0009] As mentioned above, embodiments of this disclosure include an organic / oil mixture for forming an emulsion used to form microcapsules of this disclosure. The organic / oil mixture comprises 0.1 to 20 wt% avermectin; 10 to 70 wt% a nonpolar solvent having a Hansen solubility parameter (P) value of 0 to 3; and 0.5 to 80 wt% a polar solvent of formula I.

[0010]

[0011] Wherein R1 is a C1 to C15 alkyl; R2 is H or C1 to C8 alkyl; R3 is C1 to C15 alkylene; and R4 is C1 to C15 alkyl, wherein the total carbon in R1, R2, R4 alkyl and R3 alkylene is 8 to 30; and 2.5 to 20% by weight of isocyanate, wherein each % by weight is based on the total weight of the organic / oil mixture, and the total weight of avermectin, nonpolar solvent, polar solvent and isocyanate is 100% by weight.

[0012] An organic / oil mixture is used in an emulsion comprising an organic / oil mixture and an aqueous mixture. The organic / oil mixture of the emulsion comprises 0.1 to 10 wt% (w%) of avermectin; 10 to 30 wt% of a nonpolar solvent; and 0.5 to 30 wt% of a polar solvent of formula I.

[0013]

[0014] Wherein R1 is a C1 to C15 alkyl; R2 is H or C1 to C8 alkyl; R3 is a C1 to C15 alkylene; and R4 is a C1 to C15 alkyl, wherein the total carbon content of the alkyl groups R1, R2, R4, and R3 is 8 to 30; and 2.5 to 10% by weight of isocyanate. The aqueous mixture comprises 0.5 to 20% by weight of surfactant; 0.5 to 20% by weight of dispersant; 0.01 to 2% by weight of thickener; and 40 to 55% by weight of water, wherein each % by weight of the emulsion is based on the total weight of the emulsion, and the sum of the % by weight of the organic / oil mixture and the aqueous mixture is 100% by weight.

[0015] Preferably, R1 is a C1 to C8 alkyl group; R3 is a C1 to C8 alkylene group; and R4 is a C1 to C8 alkyl group. Preferably, the total number of carbon atoms in the alkyl groups R1, R2, R4, and R3 is 10 to 25. Most preferably, the polar solvent is 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate.

[0016] As described herein, nonpolar solvents have a Hansen solubility parameter polarity (P) value of 0 to 3, wherein such nonpolar solvents are selected from the group consisting of aromatic petroleum derivatives, vegetable oils, hydrocarbons, esters, amides, and combinations thereof. In a preferred embodiment, the nonpolar solvent is Solvesso. TM 150# (ExxonMobil Co.), is an aromatic petroleum derivative.

[0017] For various embodiments, the isocyanate is selected from the group consisting of: methylene diphenyl diisocyanate (MDI), polymeric MDI, hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), 1,5-naphthalene diisocyanate (NDI), methylene dicyclohexyl isocyanate (HMDI), isophorone diisocyanate (IPDI), and combinations thereof.

[0018] For aqueous mixtures, the surfactant is a branched alcohol alkoxylate. The dispersant is an acrylate-based dispersant polymer. The thickener is selected from the group consisting of natural polysaccharides, inorganic silicates, synthetic polymers, clays, or combinations thereof.

[0019] This disclosure also includes microcapsules comprising a coating formed by reacting an amine with an isocyanate in an emulsion as provided herein, and a liquid mixture contained within the coating forming the microcapsules, wherein the liquid mixture comprises avermectin, a nonpolar solvent, a polar solvent, a surfactant, a dispersant, a thickener, and water. The microcapsules are suspended in the aqueous mixture. Detailed Implementation

[0020] This disclosure provides improvements in the microencapsulation of avermectin. In particular, it provides an active solution with a solvent that exhibits good avermectin solubility, achieves a target avermectin loading level (3 to 5% by weight), and has good hydrophobicity to facilitate capsule formation while minimizing avermectin degradation during the capsule formation process. Specifically, it has been surprisingly found that the use of a specific polar solvent in combination with a nonpolar solvent in what is referred to herein as an organic / oil mixture (discussed herein) allows the weight percentage of avermectin contained in the microcapsules to be comparable to the weight percentage of avermectin in the organic / oil mixture used to form the microcapsules. In other words, the surprisingly close weight percentage of avermectin in the microcapsules to the weight percentage of avermectin in the organic / oil mixture used to form the microcapsules indicates that avermectin is unexpectedly well protected during the encapsulation reaction.

[0021] As provided herein, organic / oil mixtures are used in conjunction with aqueous mixtures to form emulsions. An amine is added to the emulsion, wherein, through an interfacial polymerization process, the amine reacts with isocyanates present in the organic / oil mixture to form a coating around the organic / oil mixture, thereby forming microcapsules of this disclosure. The liquid mixture contained within the coating forming the microcapsules comprises avermectin.

[0022] Organic / oil mixture

[0023] Embodiments of this disclosure include an organic / oil mixture for forming an emulsion, which is subsequently used to form microcapsules of this disclosure. The organic / oil mixture comprises 0.1 to 20 wt% avermectin; 10 to 70 wt% a nonpolar solvent having a Hansen solubility parameter polarity (P) value of 0 to 3; and 0.5 to 80 wt% a polar solvent of formula I.

[0024]

[0025] Wherein R1 is a C1 to C15 alkyl; R2 is H or C1 to C8 alkyl; R3 is C1 to C15 alkylene; and R4 is C1 to C15 alkyl, wherein the total carbon in R1, R2, R4 alkyl and R3 alkylene is 8 to 30; and 2.5 to 20% by weight of isocyanate, wherein each % by weight is based on the total weight of the organic / oil mixture, and the total weight of avermectin, nonpolar solvent, polar solvent and isocyanate is 100% by weight.

[0026] The organic / oil mixture comprises 0.1 to 20% by weight of avermectin, where the weight percentage is based on the total weight of the organic / oil mixture. Preferably, the organic / oil mixture comprises 0.1 to 10% by weight of avermectin. In a preferred embodiment, the organic / oil mixture comprises 3 to 5% by weight of avermectin. Avermectin (CAS Registry No. 71751-41-2) is a mixture containing more than 80% by weight of avermectin B1a (CAS Registry No. 65195-55-3) and the remainder (i.e., up to 100% by weight) of avermectin B1b (CAS Registry No. 65195-56-4). Avermectin is an insecticide derived from the soil bacterium *Streptomyces avermitilis*. Avermectin is available from commercial sources such as Hebei Weiyong Bio-Chemical Co., Ltd.

[0027] While this disclosure uses avermectin, it should be understood that other bioactive compounds having hydroxyl groups similar to avermectin may be used in conjunction with organic / oil mixtures to form the emulsions and microcapsules of this disclosure. Such bioactive compounds may include, but are not limited to, macrolides, including avermectin (ivermectin, avermectin, and doramectin) and milbemycins (milbemycin oxime and moxidectin).

[0028] The organic / oil mixture also includes 10 to 70% by weight of a nonpolar solvent with a Hansen solubility parameter polarity (P) value of 0 to 3, wherein the weight percentage is based on the total weight of the organic / oil mixture. Preferably, the organic / oil mixture includes 20 to 60% by weight of a nonpolar solvent. Generally, available nonpolar solvents for use in this disclosure include, but are not limited to, agriculturally acceptable hydrophobic solvents having low water solubility (e.g., less than 0.1% by weight) at room temperature (e.g., 23°C) and a Hansen solubility parameter polarity (P) value of 0 to 3. As used herein, the Hansen solubility parameter website ( https: / / www.hansen-solubility.com / buy-HSPiP-software.phpSoftware available online can be used to calculate the polarity (P) value of the Hansen solubility parameter. The polarity (P) value of the Hansen solubility parameter can also be calculated based on: *Hansen Solubility Parameters: A user's handbook, Second Edition.*, Boca Raton, Florida, CRC Press, ISBN 978-0-8493-7248-3. The polarity values ​​of the Hansen solubility parameter provided in this article were measured at room temperature (23°C).

[0029] These nonpolar solvents are selected from the group consisting of aromatic petroleum derivatives, vegetable oils, hydrocarbons, esters, amides, and combinations thereof. Examples of aromatic petroleum derivatives include those marketed under the trade name Solvesso. TM 100. Solvesso TM 150. Solvesso TM 200, Solvesso TM 150ND, Solvesso TM 200ND, Aromatic TM 150. Aromatic TM 200, Hydrosol TM A200, Hydrosol TM A 230 / 270, Caromax TM 20. Caromax TM 28. Aromat TM K 150, Aromat TM K 200 and Shellsol TM A 150, etc., are those commercially available from ExxonMobil or British Petroleum. In a preferred embodiment, the nonpolar solvent is Solvesso. TM 150# (ExxonMobil) is an aromatic petroleum derivative. Examples of vegetable oils include soybean oil, rapeseed oil, palm oil, and corn oil. Examples of hydrocarbons include pentane, hexane, straight-chain alkanes, isoalkanes, and cycloalkanes. Examples of esters include, but are not limited to, terpene esters, benzyl acetate, and benzyl benzoate. Examples of amides include N,N-dialkylamides, commercially available from The PC Hall Co. as Hallcomide M 810, and from Clariant Corporation as Genagen 4166. Any combination of the above nonpolar solvents may also be used.

[0030] The organic / oil mixture further comprises 0.5 to 80% by weight of a polar solvent of Formula I, wherein the weight percentage is based on the total weight of the organic / oil mixture. Preferably, the organic / oil mixture comprises 10 to 70% by weight of a polar solvent. In contrast to non-polar solvents, the polarity (P) value of the Hansen solubility parameter of the polar solvents disclosed herein is greater than 3 to 10, as measured / calculated according to the methods discussed herein for non-polar solvents. As described above, the polar solvent is represented by Formula I:

[0031]

[0032] Wherein R1 is a C1 to C15 alkyl; R2 is H or a C1 to C8 alkyl; R3 is a C1 to C15 alkylene; and R4 is a C1 to C15 alkyl, wherein the total carbon content of the alkyl groups R1, R2, R4, and R3 is 8 to 30; and 2.5 to 20% by weight of isocyanate, wherein each % by weight is based on the total weight of the organic / oil mixture, and the total % by weight of avermectin, nonpolar solvent, polar solvent, and isocyanate is 100% by weight. Preferably, R1 is a C1 to C8 alkyl; R4 is a C1 to C8 alkyl; and R3 is a C1 to C8 alkylene. Preferably, the total carbon content of the alkyl groups R1, R2, R3, and R4 is 10 to 25. Most preferably, the polar solvent is 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (IBT).

[0033] As presented herein, the use of polar solvents helps protect avermectin from degradation during microencapsulation. Specifically, the hydroxyl groups in polar solvents help reduce avermectin degradation that may result from reactions between isocyanate groups and the hydroxyl groups in avermectin. Polar solvents also contribute to the formation of stable emulsions and microencapsulation suspensions, even under cold and heat aging tests and UV stability tests, as seen in the examples section below.

[0034] Examples of suitable polar solvents disclosed herein include, but are not limited to, solvents having solubility parameters similar to the aforementioned ester alcohols. Examples of such polar solvents include butyl formate (CAS 592-84-7), diethylene glycol hexyl ether (CAS 112-59-4), dipropylene glycol monobutyl ether (CAS 29911-28-2), ethylene glycol monoethyl ether acrylate (CAS 106-74-1), meclofenac (CAS 51-68-3), methanol clusters (CAS 67-56-1), methyl acrylate (CAS 96-33-3), propylene glycol monomethyl ether acetate (CAS 108-65-6), propylene glycol monopropyl ether (CAS 1569-01-3), 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate (CAS 25265-77-4), vinyl crotonate (CAS 14861-06-4), vinyl formate (CAS 14861-06-4), and methyl ethyl ether (CAS 1569-01-3). 692-45-5), 2,2,3,4,4,4-hexafluorobut-1-ol (CAS 382-31-0), 1,1,1-trifluoro-2-methylprop-2-ol (CAS 507-52-8), 1-pentanol, 2,2,3,3,4,4,5,5-octafluoro (CAS 355-80-6), ethyl 2-methyl-3-hydroxy-4,4,4-trifluorobutyrate (CAS 91600-33-8), and propylene glycol 2-tert-butyl ether (CAS 94023-15-1).

[0035] The organic / oil mixture further comprises 2.5 to 30% by weight of isocyanate, wherein the weight percentage is based on the total weight of the organic / oil mixture. Preferably, the organic / oil mixture comprises 5 to 20% by weight of isocyanate. The isocyanates disclosed herein may include, but are not limited to, methylene diphenyl diisocyanate (MDI), polymeric MDI (PDMI), hexamethylene diisocyanate (HDI), toluene diisocyanate (TDI), 1,5-naphthalene diisocyanate (NDI), methylene dicyclohexyl isocyanate (HMDI), isophorone diisocyanate (IPDI), and combinations thereof. Suitable isocyanates may also include other aromatic and / or aliphatic polyfunctional isocyanates. Aromatic isocyanates include those containing a phenyl, tolyl, xylyl, naphthyl, or diphenyl moiety or combinations thereof, such as trimethylolpropane adduct of xylene diisocyanate, trimethylolpropane adduct of toluene diisocyanate, 4,4'-diphenyldimethane diisocyanate (MOI), xylene diisocyanate (XDI), 4,4'-diphenyldimethylmethane diisocyanate, dialkyldiphenylmethane diisocyanate and tetraalkyldiphenylmethane diisocyanate, 4,4'-dibenzyl diisocyanate, 1,3-phenylene diisocyanate, 1,4-phenylene diisocyanate and combinations thereof. Suitable aliphatic polyfunctional isocyanates include trimers of hexamethylene diisocyanate, trimers of isophorone diisocyanate, biuret of hexamethylene diisocyanate, hydrogenated methylene diphenyl diisocyanate, hydrogenated methylene diphenyl diisocyanate, hydrogenated MDI, tetramethylxylene diisocyanate (TMXDI), 1-methyl-2,4-diisocyanocyclohexane, 1,6-diisocyanate-2,2,4-trimethylhexane, 1-isocyanomethyl-3-isocyano-1,5,5-trimethylcyclohexane, tetramethoxybutane 1,4-diisocyanate, butane 1,4-diisocyanate, hexane 1,6-diisocyanate, dicyclohexylmethane diisocyanate, cyclohexane 1,4-diisocyanate, and combinations thereof.

[0036] lotion

[0037] Organic / oil mixtures are used in emulsions, wherein the emulsion comprises an organic / oil mixture and an aqueous mixture. As used herein, the aqueous mixture comprises water, a surfactant, a thickener, and a dispersant, wherein an amine is added after the emulsion is formed to crosslink the isocyanate and form the wall of the microcapsules of this disclosure.

[0038] The organic / oil mixture of the emulsion comprises 0.1 to 10 wt% (w%) of avermectin; 10 to 30 wt% of a nonpolar solvent; and 0.5 to 30 wt% of a polar solvent of formula I.

[0039]

[0040] Wherein R1 is a C1 to C15 alkyl; R2 is H or C1 to C8 alkyl; R3 is a C1 to C15 alkylene; and R4 is a C1 to C15 alkyl, wherein the total carbon content of the alkyl groups R1, R2, R4, and R3 is 8 to 30; and 2.5 to 10% by weight of isocyanate. The aqueous mixture comprises 0.5 to 20% by weight of surfactant; 0.5 to 20% by weight of dispersant; 0.01 to 2% by weight of thickener; and 40 to 55% by weight of water, wherein each % by weight of the components of the emulsion is based on the total weight of the emulsion, and the sum of the % by weight of the organic / oil mixture and the aqueous mixture is 100% by weight.

[0041] Examples of avermectin, nonpolar solvents, polar solvents, and isocyanates are described above. Preferably, the organic / oil mixture of the emulsion comprises 0.1 to 10 wt% avermectin; 10 to 30 wt% nonpolar solvent; 0.5 to 30 wt% polar solvent of Formula I; and 2.5 to 10 wt% isocyanate, as described above. More preferably, the organic / oil mixture of the emulsion comprises 3 to 5 wt% avermectin; 10 to 22 wt% nonpolar solvent; 25 to 27 wt% polar solvent of Formula I; and 4 to 8 wt% isocyanate.

[0042] The aqueous mixture comprises 0.5 to 20% by weight of a surfactant. Preferably, the aqueous mixture comprises 1 to 10% by weight of a surfactant, and more preferably, the aqueous mixture comprises 2 to 8% by weight of a surfactant. Examples of surfactants include, but are not limited to, branched alcohol alkoxylates, ethylene oxide / propylene oxide (EO / PO) copolymers, dialkyl sulfosuccinates, phosphate-based surfactants, alkyl diphenyl ether disulfonate surfactants, and anionic sulfonate or sulfate surfactants, and any combination thereof. Preferably, the surfactant is a branched alcohol alkoxylate. As provided herein, the branched alcohol alkoxylate may include primary and / or secondary branched alcohol alkoxylates.

[0043] Examples of primary branched alcohol ethoxylates include, for example, those marketed under the name ECOSURF. TM such as ECOSURF TM EH-9, ECOSURF TM EH-9 and its combination are commercially available products. Secondary branched alcohol ethoxylates include, for example, those marketed under the name Tergitol. TM 15-S-9, Tergitol TM Commercially available products including 15-S-12 and combinations thereof. Examples of EO-PO copolymers include those marketed under the trade name Tergitol. TM L-61 and Tergitol TM L-64, DowfaxTM D-800, Dowfax TM D-850 and its combination of commercially available products. Examples of dialkyl sulfosuccinates include, for example, those marketed under the name Triton. TM GR-7M, Triton TM GR-5M and its combinations are commercially available. Examples of phosphate esters include those marketed under trade names such as Triton. TM H-55, Triton TM H-66, Triton TM QS-44 and Triton TM XQS-20 and its combination are commercially available products. Alkyl polyglycosides include, for example, those traded under names such as Triton. TM CG-50, Triton TM CG-110, Triton TM CG-600, Triton TM CG-650 and its combinations are commercially available products. Alkyl diphenyl ether disulfonates include, for example, those marketed under trade names such as Dowfax. TM 2A1, Dowfax TM Commercially available products such as 8390 and its mixtures. Sulfonate or sulfate surfactants include, for example, sodium dodecyl sulfate, sodium dodecylbenzene sulfonate, and sodium dodecylnaphthalene sulfate, under trade names such as Triton. TM QS-15, Triton TM XN-45 and its combination of commercially available products.

[0044] The aqueous mixture comprises 0.5 to 20% by weight of a dispersant. Preferably, the aqueous mixture comprises 1 to 10% by weight of a dispersant, and more preferably, the aqueous mixture comprises 2 to 8% by weight of a dispersant. Preferably, the dispersant is an acrylate-based dispersant polymer. Examples of dispersants include, but are not limited to, copolymers of maleic acid or maleic anhydride with olefins (e.g., isobutylene or diisobutylene), copolymers of polyacrylic acid and methacrylic acid grafted with polyoxyethylene, copolymers of acrylates and acrylic acid or methacrylic acid, and combinations thereof. Specific examples include, but are not limited to, commercially available products such as Geropon T / 36 and Powerblox. TM D-305, Powerblox TM D-205, Oratan TM 731A and its combinations.

[0045] The aqueous mixture includes 0.01 to 2% by weight of a thickener. Preferably, the aqueous mixture includes 0.05 to 1% by weight of a thickener. The thickener is selected from the group consisting of natural polysaccharides, inorganic silicates, synthetic polymers, clays, or combinations thereof. Examples of natural polysaccharides include, but are not limited to, xanthan gum, carrageenan, and locust bean gum. Examples of inorganic silicates include, but are not limited to, compounds in the form of silica, magnesium aluminum silicate, and montmorillonite. Examples of synthetic polymers include, but are not limited to, polyurethanes. Examples of clays include those known in the art.

[0046] The aqueous mixture also includes 40 to 55% by weight of water. As is known in the art, the water may be deionized water or ultrafiltered water.

[0047] Microcapsules

[0048] As provided herein, the microcapsules of this disclosure comprise a coating formed by reacting an amine with an isocyanate present in an organic / oil mixture of emulsions. The microcapsules also include a liquid mixture contained within the coating forming the microcapsules. The liquid mixture within the microcapsules comprises avermectin, a nonpolar solvent, a polar solvent, a surfactant, a dispersant, a thickener, and water. The microcapsules are suspended in an aqueous mixture.

[0049] Amines that can be used to form the microcapsules of this disclosure include, but are not limited to, ethylamine, ethylenediamine, triethylenetetramine, 1,6-hexamethylenediamine, bis-hexamethylenetriamine, dimethylamine, tetraethylenepentamine, trimethylamine, diethylamine, diisopropylamine, dimethylaminopropylamine, triisopropylamine, polyamines, or combinations thereof. Other well-known water-soluble amines may also be used to form the microcapsules of this disclosure. Monomers that can react with isocyanate monomers to produce microcapsule walls may also be compounds containing active hydrogen, such as water-soluble diols or polyols, for example, ethylene glycol, triethylene glycol, propylene glycol, and dipropylene glycol.

[0050] Microcapsule preparation is an interfacial polymerization process using polyurea / polyurethane chemistry, where isocyanate monomers contribute to the formation of the microcapsule wall. However, avermectin includes hydroxyl functional groups, which may react during the encapsulation process, thus posing a risk of reactive degradation. Surprisingly, however, this disclosure has found that, as provided herein, the use of specific polar solvents in combination with nonpolar solvents produces microcapsules containing a weight percentage of avermectin comparable to the weight percentage of avermectin in the organic / oil mixture used to form the microcapsules. In other words, the weight percentage of avermectin in the microcapsules is surprisingly close to the weight percentage of avermectin in the organic / oil mixture used to form the microcapsules.

[0051] To form microcapsules, a nonpolar solvent and a polar solvent of the organic / oil mixture were mixed at room temperature (23°C). An isocyanate was then added to the nonpolar / polar solvent mixture, followed by avermectin, to form the organic / oil mixture. The organic / oil mixture was then mixed using a top-mounted stirrer (e.g., at 200 to 300 rpm for 5 to 10 minutes) to form a homogeneous mixture.

[0052] Similarly, an aqueous mixture is prepared by mixing (one or more) surfactants, (one or more) dispersants, thickeners, and water (e.g., deionized water) at room temperature. For example, the aqueous mixture can be mixed using a top-mounted stirrer (e.g., at 200 to 300 rpm for 5 to 10 minutes) to form a homogeneous mixture. The aqueous mixture and the organic / oil mixture are then mixed to form a two-phase mixture. The two-phase mixture is then combined to form an emulsion by mixing with a top-mounted stirrer at approximately 1000 to 2000 rpm for approximately 5 to 10 minutes at room temperature. The mixing speed and duration are continued until the particle size of the organic / oil mixture in the emulsion is less than 10 micrometers, where the size is confirmed using an optical microscope.

[0053] The amine is then added to the emulsion at room temperature to form microcapsules. The amount of amine added can be from 0.1 to 5 moles per mole of isocyanate in the organic / oil mixture. The amine can be added to the emulsion as an amine solution having 5 to 20% by weight of amine in water (e.g., deionized water) based on the total weight of the amine solution. Specifically, the amine solution can be added dropwise to the emulsion at room temperature with stirring to maintain good mixing. After the amine addition is complete, the resulting microcapsule suspension is stirred at 200-500 rpm for a certain time interval (e.g., one minute).

[0054] Example

[0055] Some embodiments of this disclosure will now be described in detail in the following examples.

[0056] Raw materials:

[0057]

[0058] Microcapsule preparation

[0059] Microcapsule preparation is an interfacial polymerization process using polyurea / polyurethane chemistry, where isocyanate monomers contribute to the formation of the microcapsule walls. However, avermectin includes hydroxyl functional groups, which may react during the encapsulation process, thus posing a risk of reactive degradation. Surprisingly, however, this disclosure has found that, as provided herein, the use of specific polar solvents in combination with nonpolar solvents produces microcapsules containing a weight percentage of avermectin comparable to the weight percentage of avermectin in the organic / oil mixture used to form the microcapsules. In other words, the weight percentage of avermectin in the microcapsules is surprisingly close to the weight percentage of avermectin in the organic / oil mixture used to form the microcapsules. For example, as seen below, the weight percentage of avermectin in the microcapsules of Example 2 is the same as the weight percentage of avermectin in the organic / oil mixture at the time of microcapsule formation, indicating that avermectin is surprisingly well protected during the encapsulation reaction.

[0060] At room temperature (23°C), a nonpolar solvent, a polar solvent (when in use), and then isocyanate were mixed in the amounts listed in Tables 1 (Examples) and 2 (Comparative Examples) to form a solvent mixture. At room temperature, avermectin was added to the solvent mixture in the amounts listed in Tables 1 and 2 to form an organic / oil mixture. The organic / oil mixture was mixed using an IKA overhead stirrer at 200 to 300 rpm to form a homogeneous mixture.

[0061] An aqueous mixture was prepared by mixing (one or more) surfactants, (one or more) dispersants, thickeners, and deionized (DI) water as shown in Tables 1 and 2 at room temperature. The aqueous mixture was added to the organic / oil mixture to obtain a two-phase mixture. The two-phase mixture was emulsified at room temperature to form an emulsion by mixing with an IKA overhead stirrer at approximately 1000 rpm. The emulsification process was continued until the particle size in the emulsion was less than 10 micrometers (size confirmed using an optical microscope).

[0062] A 10 wt% (w / w) aqueous solution of ethylenediamine (EDA) was prepared to form an amine solution. At room temperature, the amine solution was added dropwise to the emulsion according to the amounts shown in Tables 1 and 2, while stirring at a reduced speed to maintain good mixing. After the amine addition was complete, the resulting microcapsule suspension was stirred for another minute at 200–500 rpm.

[0063] For the examples (Table 1) and comparative examples (Table 2), unless otherwise stated, the content of each component shown in Tables 1 and 2 is given as a weight percentage based on the total weight of the microcapsule suspension.

[0064] Table 1- Examples 1-5

[0065]

[0066] *The capsule contains approximately 0.4% butylated hydroxytoluene (BHT, a UV stabilizer).

[0067] Table 2 Comparison of Examples A and B

[0068]

[0069] Microcapsule formation was confirmed using optical and fluorescence microscopy. The microcapsules were then disrupted using pressure, and both optical and fluorescence microscopy confirmed that the contents were hydrophobic due to the formation of small droplets of the contents within the microcapsules in the aqueous phase. These observations confirmed that avermectin was well encapsulated within the microcapsules.

[0070] Test program

[0071] The example uses the following test program.

[0072] a) Thermal aging test

[0073] The percentage of avermectin in a sample of microcapsule suspension prepared as described in the microcapsule preparation section above was measured according to the method discussed in section c) below. From the same sample of microcapsule suspension prepared as described in the microcapsule preparation section above, 100 g of the microcapsule suspension was placed in a 1 L beaker and covered to prevent evaporation. The covered beaker was placed in an oven set to 54 °C and left at 54 °C for 2 weeks. After 2 weeks, the beaker was removed, and the microcapsule suspension was allowed to return to room temperature to form a heat-aged sample of the microcapsule suspension. The percentage of avermectin in the heat-aged sample of the microcapsule suspension was measured according to the method discussed in section c) below. Table 5 provides the results of these tests.

[0074] b) UV aging test

[0075] The percentage of avermectin was measured from a sample of the microcapsule suspension prepared as described in the microcapsule preparation section above, according to the method discussed in section c) below of this disclosure. From the same sample of the microcapsule suspension prepared as described in the microcapsule preparation section above, 10 g was placed in a glass vial and exposed to an energy of 100 μJ / cm² using UVP, LLC CL-1000 ultraviolet crosslinking agent. 3 UV-aged samples of microcapsule suspensions were formed by exposing the samples to ultraviolet light (wavelengths from approximately 10 nm to 400 nm) for 20 hours. The percentage of avermectin in the UV-aged samples of the microcapsule suspensions was measured according to the methods discussed in section c) below. The results of these tests are presented in Table 6.

[0076] Similarly, the percentage of avermectin was measured from a sample of the emulsion prepared as described in the microcapsule preparation section above, according to the method discussed in section c) below of this disclosure. From the same sample of the emulsion prepared as described in the microcapsule preparation section above, 10 grams were placed in a glass vial and exposed to an energy of 100 μJ / cm² using UVP, LLC CL-1000 ultraviolet crosslinking agent. 3 UV-aged samples of the emulsion were formed by exposing the emulsion to ultraviolet light (wavelengths from approximately 10 nm to 400 nm) for 20 hours. The percentage of avermectin in the UV-aged samples of the emulsion was measured according to the methods discussed in section c) below. The results of these tests are presented in Table 6.

[0077] c) Measurement of abamectin content and encapsulation efficiency

[0078] The content of avermectin in the microcapsules and the encapsulation efficiency of avermectin were determined as follows.

[0079] A 5 ml sample of the microcapsule suspension prepared in the microcapsule preparation section above was centrifuged at 5800 rpm for 10 minutes to separate the microcapsules from the aqueous phase. At room temperature, 0.1 g of the separated microcapsules were suspended in 10 ml of analytical grade methanol to form a microcapsule test sample. The microcapsule test sample was then sonicated for 10 minutes at room temperature using an ultrasonic cleaner (SK3210LHC, Shanghai Kudos Ultrasonic Instrument Co., Ltd.) to form an ultrasonically treated microcapsule sample.

[0080] The amount of avermectin in the sonicated microcapsule samples and the emulsion samples prepared as described in the microcapsule preparation section above was measured using reversed-phase high-performance liquid chromatography with a diode array detector (Agilent 1200 HPLC) and an Agilent Zorbax SDB-C18 column, 4.6*150 mm, 5 μm column, according to the parameters shown in Table 3. The encapsulation efficiency of avermectin was determined by comparing the amounts of avermectin in the sonicated microcapsule samples and the emulsion samples prepared as described in the microcapsule preparation section above.

[0081] Table 3

[0082]

[0083] result

[0084] Solubility of avermectin in solvents and in microcapsules

[0085] Loading level in suspension

[0086] As seen above, a general method for forming microcapsule suspensions involves forming an emulsion with an organic / oil mixture and an aqueous mixture, and then forming capsules around droplets of the organic / oil mixture by monomer polymerization. The avermectin loading levels achieved in this disclosure are attributed to the solvent mixture, wherein the solvent according to this disclosure has excellent compatibility with avermectin, thereby achieving the target avermectin loading levels, while also providing the necessary hydrophobicity relative to the aqueous mixture to facilitate microcapsule formation.

[0087] Table 4 below provides the solubility values ​​of avermectin in various solvents at room temperature (as a percentage of the total weight of the composition).

[0088] Table 4- Solubility of abamectin in solvents

[0089]

[0090] As shown in Table 4, the solubility of avermectin in hydrophobic solvents is very low (Comparative Examples C to G), decreasing to values ​​below 1%. These solvents include rosin vegetable oil ND-60 and the aromatic solvent Solvesso. TM 150#, these are commonly used agricultural solvents, and the use of such solvents may result in an active loading level of less than 1%, as seen in Comparative Examples A to C.

[0091] Conversely, in UCAR TM The solubility of avermectin in FILMER IBT is as high as 14.0% (Example 6), and it is also comparable to that of the aromatic solvent Solvesso. TM In the 150# combination, the solubility is greater than 10%, as seen in Table 4. Therefore, the combination of solvents and the selected weight percentages provided in this disclosure can significantly improve the solubility of avermectin and thus potentially enable high avermectin loading levels (e.g., 3% to 5% or possibly greater) in capsule suspension formulations (e.g., Examples 1-5).

[0092] Stability of avermectin in microcapsules during storage at different temperatures

[0093] As discussed above, the stability of avermectin in microcapsules during storage was assessed using a heat aging test. As shown in Table 5, heat aging of avermectin-containing microcapsules at 54°C for 2 weeks resulted in almost no loss of avermectin. This result is similar to the aging test of avermectin-containing microcapsules at 0°C for 1 week.

[0094] Table 5 – Weight percentage of avermectin in microcapsules from the sample in Example 2

[0095]

[0096] Stability of avermectin in microcapsules after exposure to UV light

[0097] As described herein, avermectin is highly sensitive to light, particularly UV light. A solution to this important problem is to encapsulate and / or incorporate avermectin with a UV stabilizer. The results of the UV aging tests discussed above are shown in Table 6. As seen in Table 6, samples of the emulsion prepared as described in the microcapsule preparation section above (Comparative Example 4, 3.18% avermectin + 15.00% NMP + 81.82% Solvesso 150#) and the microcapsule suspension of Example 4 were exposed to UV light for 20 hours, as discussed above. As shown in Table 6, without the protection of the microcapsule wall, 16.25% of avermectin was lost (Comparative Example 4), while only about 2% to 3% of avermectin was lost when contained in the microcapsules of this disclosure (Example 4) and in an example that also included a UV stabilizer internally (Example 5). This data indicates that microcapsules contribute to a significant improvement in UV stability.

[0098] Table 6- Active stability against UV aging

[0099]

[0100] *Comparative Example 4 is an EC sample, 3.18% avermectin + 15.00% NMP + 81.82% Solvesso 150#.

[0101] **Example of Invention 5: UV stabilizer BHT inside the capsule.**

Claims

1. An organic / oil mixture comprising: 0.1 to 20% by weight of avermectin; 10 to 70% by weight of a nonpolar solvent, wherein the polarity P value of the Hansen solubility parameter of the nonpolar solvent is 0 to 3, and wherein the nonpolar solvent is an aromatic petroleum derivative, Solvesso. TM 150#; 0.5 to 80% by weight of a polar solvent, wherein the polar solvent is 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate; and 2.5 to 20% by weight of isocyanate, wherein each % by weight is based on the total weight of the organic / oil mixture, and the sum of the % by weight of the abamectin, the nonpolar solvent, the polar solvent and the isocyanate is 100% by weight.

2. The organic / oil mixture according to claim 1, wherein the isocyanate is selected from the group consisting of: methylene diphenyl diisocyanate, polymeric MDI, hexamethylene diisocyanate, toluene diisocyanate, 1,5-naphthalene diisocyanate, methylene dicyclohexyl isocyanate, isophorone diisocyanate, and combinations thereof.

3. An emulsion comprising: Organic / oil mixture, the organic / oil mixture comprising: 0.1 to 10% by weight of avermectin; 10 to 30% by weight of a nonpolar solvent, wherein the polarity P value of the Hansen solubility parameter of the nonpolar solvent is 0 to 3, and wherein the nonpolar solvent is an aromatic petroleum derivative, Solvesso. TM 150; 0.5 to 30% by weight of a polar solvent, wherein the polar solvent is 2,2,4-trimethyl-1,3-pentanediol monoisobutyrate; and 2.5 to 10% by weight of isocyanate; as well as Aqueous mixture, the aqueous mixture comprising: 0.5 to 20% by weight of a surfactant, wherein the surfactant is a branched alcohol alkoxylate; 0.5 to 20% by weight of a dispersant, wherein the dispersant is an acrylate-based dispersant polymer; 0.01 to 2% by weight of thickener; and 40 to 55% by weight of water, wherein each % by weight is based on the total weight of the emulsion, and the sum of the % by weight of the organic / oil mixture and the aqueous mixture is 100% by weight.

4. The emulsion according to claim 3, wherein the isocyanate is selected from the group consisting of: methylene diphenyl diisocyanate, polymeric MDI, hexamethylene diisocyanate, toluene diisocyanate, 1,5-naphthalene diisocyanate, methylene dicyclohexyl isocyanate or isophorone diisocyanate and combinations thereof; or The thickener is selected from the group consisting of natural polysaccharides, inorganic silicates, synthetic polymers, clay, or combinations thereof.

5. A microcapsule formed by adding an amine to the emulsion of claim 3 or 4, said microcapsule comprising: The coating formed by the reaction of the amine with the isocyanate in the emulsion according to claim 3 or 4; and A liquid mixture contained within the coating forming the microcapsules, wherein the liquid mixture comprises avermectin, a nonpolar solvent, a polar solvent, a surfactant, a dispersant, a thickener, and water in the emulsion of claim 3 or 4.

6. The microcapsule of claim 5, wherein the microcapsule is suspended in the aqueous mixture of claim 3.

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