WO2015103195A1

WO2015103195A1 - Microencapsulated water/oil/water emulsions having high encapsulation efficiency

Info

Publication number: WO2015103195A1
Application number: PCT/US2014/072659
Authority: WO
Inventors: Helmut Auweter; Abiola SHITTA; Hongzhi Wang; Sven Holger Behrens; Wen Xu
Original assignee: BASF SE; Georgia Institute of Technology
Current assignee: BASF SE; Georgia Institute of Technology
Priority date: 2013-12-31
Filing date: 2014-12-30
Publication date: 2015-07-09
Anticipated expiration: 2016-06-30

Abstract

Disclosed are improved water in oil in water double emulsions that are suitable for use in combination with an active agent, such as a pesticide active ingredient, for extended release products. The double emulsions are prepared using suitable osmolytes such that the majority of the resulting emulsion droplets include a single aqueous core inside of the oil phase, which results in a more consistent and predictable release profile for the active ingredient. In many embodiments, the double emulsions may be prepared using colloidal particles as stabilizers, thus negating the need for the use of conventional emulsifiers, which reduces the potential toxicity of the double emulsion and results in a more environmentally friendly and acceptable commercial product. Additionally, in many embodiments the double emulsions are prepared such that they are encapsulated with a shell-impermeable polymer to improve encapsulation efficiency such that a greater percentage of the active agent remains in a desired location and does not "leak" into less desired portions of the emulsion. The encapsulation processes described herein result in the formation of a polymeric protective layer at both water/oil interfaces such that the two separate, distinct encapsulation layers are formed.

Description

MICROENCAPSULATED WATER/OIL/WATER EMULSIONS HAVING HIGH

ENCAPSULATION EFFICIENCY

FIELD OF THE DISCLOSURE

[0001] The present disclosure relates to water in oil in water emulsions useful for extended release applications. More particularly, the present disclosure relates to water in oil in water double emulsions that include oil droplets having a single aqueous core therein including an active agent. The present disclosure also relates to microencapsulated water in oil in water emulsions wherein the capsules include two separate polymeric layers to improve encapsulation efficiency and release profile.

BACKGROUND OF THE DISCLOSURE

[0002] Crop, field, and pest protection agents have conventionally been formulated in solid or liquid compositions, usually in the form of an emulsified concentrate for ease of handling and transportation. The concentrate is generally diluted with water by the user before application. Many liquid formulations in the form of emulsifiable or near- emulsifiable concentrates may contain a very high proportion of organic solvents (often up to 80 percent), which are increasingly coming under scrutiny for their potential negative effect on the environment.

[0003] In many cases, it is desirable for the crop, field, and pest protection agent to provide benefits over an extended period of time after application. In these cases, controlled or extended release formulations are desirable as they can regulate over time the release of a pesticide active agent to provide extended benefit and reduce the need for re- application. Water in oil in water emulsions, also commonly referred to as double emulsions, are useful templates for controlled release applications, and may be

encapsulated with a single outer layer in many embodiments. The release properties for the active agent are easiest to control and model if the majority of the templating emulsion droplets contain a single aqueous core. Such single-core droplets may be fabricated with acceptable uniformity in a droplet-by-droplet fashion using microfluidic devices, but the yield of this process is generally too limited for many applications. Further, although classical batch emulsification is easier to scale up to increase throughput, double emulsions prepared in this manner typically contain droplets with many cores droplets, which can significantly negatively impact the release profile of the active ingredient. Also, these processes typically rely on one or more emulsifiers, which may be problematic in many regions of the world.

[0004] Based on the foregoing, there is a need for methodologies that provide for increased throughput of water in oil in water double emulsions that can be prepared with a majority of the resulting droplets including a single aqueous core droplet that may include one or more pesticide active agents. It would also be beneficial if these methodologies had a reduced need for the use of conventional emulsifiers. Further, it would be desirable if these double emulsions could be further stabilized to reduce active agent transfer between aqueous phases by the formation of encapsulation layers to improve the resulting encapsulation efficiency.

SUMMARY OF THE DISCLOSURE

[0005] The present disclosure is directed to improved water in oil in water double emulsions that are suitable for use in combination with an active agent, such as a pesticide active ingredient, for extended release products and applications. The double emulsions are prepared using suitable osmolytes such that the majority of the resulting emulsion droplets include a single aqueous core inside of the oil phase, which results in a more long- term consistent and predictable release profile for the active ingredient as release of the active ingredient is not impaired by a large distribution of core sizes and a distribution of different wall thicknesses. In many embodiments, the double emulsions may be prepared using colloidal particles as stabilizers, thus negating the need for the use of conventional emulsifiers, which reduces the potential toxicity of the double emulsion and results in a more environmentally friendly and acceptable commercial product. Additionally, in many embodiments, the double emulsions are prepared such that they are encapsulated within shell-impermeable polymeric layers to improve encapsulation efficiency such that a greater percentage of the active agent remains in the desired inner aqueous phase location and does not "leak" into less desirable phases of the emulsion. The encapsulation processes described herein result in the formation of a polymeric protective layer at both water/oil interfaces of the double emulsion such that the two separate, distinct encapsulation layers are formed to further protection of the active agent. [0006] The present disclosure is further directed to a process for preparing a water in oil in water emulsion comprising oil droplets having a single aqueous core droplet. The process comprises: emulsifying a first aqueous solution in a non-aqueous dispersion to form a first water in oil emulsion, wherein the first aqueous solution includes osmolytes and the non-aqueous dispersion includes colloidal particles; emulsifying the first water in oil emulsion in a second aqueous solution to form a water in oil in water emulsion, wherein the second aqueous solution has an osmotic concentration that is less than an osmotic concentration of the first aqueous solution; and allowing for osmotic swelling and coalescence to occur such that droplets of the first aqueous solution having a single aqueous core form inside of the non-aqueous dispersion.

[0007] The present disclosure is further directed to a process for preparing a water in oil in water emulsion comprising oil droplets having a single aqueous core droplet. The process comprises: emulsifying a first aqueous solution in a non-aqueous dispersion to form a first water in oil emulsion, wherein the first aqueous solution includes osmolytes and the non-aqueous dispersion includes colloidal particles; emulsifying the first water in oil emulsion in a second aqueous solution to form a water in oil in water emulsion, wherein the second aqueous solution has an osmotic concentration that is less than an osmotic concentration of the first aqueous solution; allowing for osmotic swelling and coalescence to occur such that droplets of the first aqueous solution having a single aqueous core form inside of the non-aqueous dispersion; and reducing a diameter of the single aqueous core from inside of the non-aqueous dispersion by increasing an osmotic concentration of the second aqueous solution to a level greater than the osmotic concentration of the first aqueous solution.

[0008] The present disclosure is further directed to a process for preparing a microcapsule having a first polymer shell, a second polymer shell, and an aqueous core. The process comprises: emulsifying a first aqueous solution comprising a first water- soluble reactant for an interfacial polymerization reaction in a non-aqueous solution comprising a first emulsion stabilizer to produce a water in oil emulsion; introducing an oil-soluble reactant into the water in oil emulsion and allowing the formation of a first polymer shell by interfacial polymerization at an interface of the water in oil emulsion to produce an oil-continuous capsule dispersion of aqueous core polymer capsule; emulsifying the oil-continuous capsule dispersion of aqueous core polymer capsule in a second aqueous solution comprising a second emulsion stabilizer to produce a water in oil in water emulsion; and introducing a second water-soluble reactant into the water in oil in water emulsion and allowing the formation of a second polymer shell by interfacial polymerization at an interface of the water in oil in water emulsion to produce the microcapsule.

[0009] The present disclosure is further directed to an extended release microcapsule comprising a water in oil in water emulsion, a first polymer shell at a first water and oil interface and a second polymer shell at a second water and oil interface, wherein the emulsion includes a pesticide active ingredient in an inner aqueous core.

[0010] The present disclosure is further directed to a method for controlling phytopathogenic fungi and/or undesired vegetation and/or undesired attack by insects or mites and/or for regulating the growth of plants, where the extruded pesticide granular composition of any of claims 11-19 is allowed to act on the respective pests, their environment or on the crop plants to be protected from the respective pests, on the soil and/or on undesired plants and/or on the crop plants and/or their environment.

[0011] It has been unexpectedly found that in the case of particle-stabilized double emulsions, osmotic swelling enables the formation of single aqueous core droplets inside of the oil phase of the double emulsion. Surprisingly, by using osmotic morphology control with the double emulsions, core droplets can be suitably stabilized by a small amount of colloidal particles. Advantageously, inner aqueous droplets with a higher osmotic concentration than the continuous oil phase will swell and their enlarged surface will be unable to be stabilized by the colloidal particles, which results in the core droplets undergoing coalescence until the aqueous core consists essentially of a single droplet. Further, upon reversing the osmotic concentration difference (through the addition of additional osmolytes to the continuous phase in a separate step), the size of the single core droplet may be reduced/controlled to a desired level.

[0012] Additionally, it has been discovered that both interfaces of a water in oil in water double emulsion may be encapsulated with a shell-impermeable polymeric material using interfacial polymerization to further improve the stability and performance of the extended release product. Two separate polymer shells and an intermediate oil phase protect the encapsulated active agent, thus providing for surprisingly high encapsulation efficiency. Also, the use of colloidal particles as emulsion stabilizers may additionally allow for the incorporation of the particles into the polymer shells to increase effectiveness, while reducing the potential of unwanted chemical interaction between conventional emulsion stabilizers and the active agent.

BRIED DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 is a photograph showing water in oil in water double emulsion droplets immediately after formation in accordance with one embodiment of the present disclosure as described in Example 1.

[0014] Figure 2 is a photograph showing the droplets of Figure lone hour after formation.

[0015] Figure 3 is a photograph showing the droplets of Figure 1 in their final state wherein the majority of the oil droplets include a single aqueous core droplet four hours after formation.

[0016] Figure 4 is a photograph showing the droplets of Figure 1 prior to a de- swelling step.

[0017] Figure 5 shows the droplets of Figure 4 after 1 hour of de-swelling wherein the single aqueous core size has been reduced significantly.

[0018] Figure 6 is a graph showing the extended release profile of microcapsules produced in Example 4 as compared to a commercially available herbicide.

DETAILED DESCRIPTION OF THE DISCLOSURE

[0019] The particle stabilized water in oil in water double emulsions including a single aqueous core of the present disclosure provide for an improved delivery vehicle for active agents, including pesticide active agents, while reducing conventional reliance on potentially environmentally unfriendly emulsification agents. By providing double emulsions that include single aqueous core droplets, the double emulsions provide better overall active agent stability and more predictable release patterns for the active agent over time. By using osmotic swelling to control the formation of the single core aqueous droplets, the droplet size and consistency is greatly improved in a high throughput process.

[0020] In many embodiments described herein, the double emulsions are further enhanced through the formation of two polymer shells at the water/oil interfaces of the double emulsion. In this embodiment, two intermediate polymer shells and an intermediate oil phase protect the encapsulated active agent and provide for surprisingly high encapsulation efficiency and improved extended release profiles as the active agent is more consistently held in the inner aqueous phase of the double emulsion and "leakage" is substantially reduced.

[0021] These and other optional elements or limitations of the extruded pesticide granules and methods of the present disclosure are described in detail hereinafter.

[0022] The term "shell-impermeable" as used herein refers to a polymer shell that prevents at least ninety percent, more desirably greater than ninety- five percent, and desirably greater than ninety-nine percent of the encapsulated material from being introduced into the surroundings until it is ruptured.

[0023] The term "microcapsule" as used herein refers to a spherical or nearly spherical structure ranging in diameter from about 1.0 micrometer to about 2500 micrometers composed of at least one polymer shell surrounding encapsulated media, and includes at least two separate and distinct polymer shells surrounding encapsulated media.

[0024] The terms "extended release," "prolonged release," and "sustained release" as used herein refer to diffusion-based release of an active agent for greater than one day, desirably greater than five days, desirably greater than one week, desirably greater than two weeks, and desirably greater than three weeks.

[0025] The term "emulsion" as used herein refers to a suspension of one solution or suspension in another in which it is immiscible, in some applications in the presence of one or more emulsion stabilizers. [0026] The term "water in oil in water emulsion" as used herein refers to a double emulsion wherein an aqueous phase, in some embodiments including a dissolved or dispersed active agent, such as a pesticide active ingredient, is dispersed in an oil phase that is subsequently dispersed into a second water phase.

[0027] The term "rupture strength" as used herein refers to the force required to break the microcapsule wall and release the encapsulated media.

[0028] The term "osmolyte" as used herein refers to a compound that affects osmosis.

[0029] The term "about" or "approximately" refers to an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitation of the measurement system, i.e., the degree of precision required for a particular purpose. For example, "about" can mean within one or more than one standard deviations of the mean, per the practice in the art. Alternatively, "about" can mean a range within five-fold, and more desirably within two-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term "about" means within an acceptable error range for the particular value.

[0030] Numerical ranges as used herein are intended to include every number and subset of numbers within that range, whether specifically disclosed or not. Further, these numerical ranges should be construed as providing support for a claim directed to any number or subset of numbers in that range. For example, a disclosure of from 1 to 10 should be construed as supporting a range of from 2 to 8, from 3 to 7, from 5 to 6, from 1 to 9, from 3.6 to 4.6, from 3.5 to 9.9, and so forth.

[0031] All combinations of method or process steps as used herein can be performed in any order, unless otherwise specified or clearly implied to the contrary by the context in which the referenced combination is made.

[0032] The emulsions and products described herein and corresponding manufacturing methods and uses of the present disclosure can comprise, consist of, or consist essentially of the essential elements and limitations of the disclosure as described herein, as well as any additional or optional ingredients, components, or limitations described herein or otherwise useful in pesticide applications.

Preparation of Water In Oil In Water Double Emulsion

[0033] The water in oil in water double emulsions of the present disclosure include oil droplets having a majority of single aqueous core droplets. As discussed hereinbelow, this aqueous core droplet will generally include at least one active agent, such as a pesticide active agent, for providing a desired benefit. The active agent may be a substantially water-soluble active agent that is dissolved in the aqueous core droplet, or it may be a substantially insoluble active agent that is suspended or dispersed in the aqueous core droplet. In the water in oil in water emulsions as described herein, the active agent is held in the inner-most aqueous droplet of the emulsion, which results in improved extended release profiles and reduces the amount of active agent lost or leaked prematurely.

[0034] The oil in water in oil emulsions including the aqueous core droplet are prepared in accordance with the present disclosure by first emulsifying a first aqueous solution in a non-aqueous dispersion so as to form a first water in oil emulsion. In some embodiments, the first oil in water emulsion may include from about 50wt.% to about 90wt.% aqueous phase and from about 10wt.% to about 50wt.% non-aqueous phase, including from about 60wt.% to about 70wt.% aqueous phase and from about 30wt.% to about 40wt.% non-aqueous phase.

[0035] The first aqueous solution may include one or more active agents dissolved, suspended, and/or dispersed therein, including both substantially soluble active agents and substantially insoluble active agents. Many suitable pesticide active agents are described hereinbelow, and other known active agents are within the scope of the present disclosure. The first water in oil emulsion may be formed using any conventional emulsion forming technology known in the art including for example various types of mixers, blenders, etc. For example, in one embodiment, the emulsion may be formed using a conventional rotor-stator mixer at 8000 rpm for a period of about 10 seconds or so. [0036] Additionally, the first aqueous solution will include one or more osmolytes. As described in more detail herein, the use of the osmolytes in the present disclosure has been surprisingly found to allow for osmotic swelling with a particle- stabilized double emulsion ("Pickering" type double emulsions) that results in the formation of single core aqueous droplets. Through osmotic morphology control of the double emulsion, inner droplets with a higher osmotic concentration than a surrounding continuous phase will swell and their enlarged surface area is no longer capable of being stabilized by the presence of the particles; this results in the core droplets undergoing coalescence until the aqueous core essentially consists of a single droplet. Additionally, and importantly, upon reversing the osmotic concentration difference (by adding a larger amount of osmolytes to the continuous phase as described herein), the size of the single core droplet can be controlled/reduced.

[0037] Suitable osmolytes for use in the first aqueous solution include, for example, electrolytes, ammonia salts, sodium chloride, sodium bromide, sodium iodide, sodium sulfate, sodium nitrate, sodium acetate, sodium citrate, sodium phosphate, potassium salts, calcium salts, magnesium salts, aluminum salts, polyelectrolytes, sugars, sugar alcohols, oligo- and poly-saccharides, and combinations thereof. The osmolyte is generally in the first aqueous solution in an amount of from about lwt.% to about 10wt.%, including from about lwt.% to about 8wt.%, including from about 2wt.% to about 7 wt.%, including from about 3wt.% to about 6wt.%, including about 5wt.%.

[0038] As noted above, the non-aqueous dispersion includes colloidal particles dispersion into a non-aqueous medium. The non-aqueous medium may be any suitable non-aqueous liquid suitable for forming the desired emulsion including for example, organic solvents such as trimethylolpropane trimethacrylate (TMPTMA), vegetable oils, mineral oils, and the like as well as common organic solvents used in pesticide

formulations such as aromatic 200/Solvesso 200, 2-Hepatnone, Agnique AMD810, Purasolv EHL, Acetophenone, Jeffsol AG 1555, etc.

[0039] The colloidal particles present in the non-aqueous medium act to stabilize the double emulsion subsequently formed in the manufacturing process. The use of colloidal particles significantly reduces or eliminates the need for conventional monomeric and/or polymeric emulsifiers, although small amounts may be used in some embodiments. Suitable colloidal particles are known in the art and may include for example, nanoparticles of a wide range of materials, inorganic particles like hydrophobic silica particles, polymeric (dispersion) particles, calcium carbonate or metal hydroxide particles, polymeric particles (such as polylactic acid, polystyrene, polyacrylates, polyesters, copolymers like poly(lactic- co-glycolic acid), microcrystalline cellulose, and the like and combinations thereof. In some embodiments, the colloidal particles may have an average diameter of from about 5 nanometers to about 5 micrometers, including from about 7 nanometers to about 200 nanometers. Generally, the colloidal particles present in the non-aqueous dispersion will be present in an amount of from about 0.001wt.% to about 5.0wt.%, including from about 0.005wt% to about 0.5wt.%.

[0040] Once the first water in oil emulsion has been formed, it is emulsified in a second aqueous solution (i.e., the continuous phase) to form the final water in oil in water double emulsion. In some embodiments, the final oil in water in oil double emulsion may include from about 10wt.% to about 30wt.% first water in oil emulsion and from about 70wt.% to about 90wt.% second aqueous solution, including from about 20wt.% to about 25wt.% first water in oil emulsion and from about 75wt.% to about 80wt.% second aqueous solution.

[0041] The second aqueous solution has an osmotic concentration that is less than the osmotic concentration of the first aqueous solution described above such that osmotic swelling as described hereinbelow may occur. The water in oil in water emulsion may be formed using any conventional emulsion forming technology known in the art including for example various types of mixers, blenders, etc. For example, in one embodiment, the water in oil in water emulsion may be formed through homogenization using a

conventional variable speed vortex mixer at the maximum speed for a period of about two minutes.

[0042] The second aqueous solution may be colloid particle-free, or may include colloidal particles to further the stabilization of the resulting water in oil in water double emulsion. In some embodiments, the second aqueous solution may optionally include one or more conventional monomeric or polymeric emulsifiers. Suitable colloidal particles are known in the art and may include for example, inorganic particles like silica particles or metal hydroxide particles, polymeric particles (such as polylactic acid, polystyrene, polyacrlylates, polyesters, copolymers like poly(lactic-co-glycolic) acid), microcrystalline cellulose, and the like and combinations thereof. In some embodiments, the colloidal particles may have an average diameter of from about 5 nanometers to about 5

micrometers, including from about 7 nanometers to about 200 nanometers. Generally, the colloidal particles present in the non-aqueous dispersion will be present in an amount of from about 0.001wt.% to about 5.0wt.%, including from about 0.005wt% to about 3.0wt.%, including about 2.0wt.%.

[0043] Once the water in oil in water double emulsion has been formed as described above, it is allowed to settle for a period of about 30 minutes, or even about 1 hour, or even about 2 hours, or even about 3 hours, or desirably about four hours to allow for osmotically driven swelling and coalescence of the aqueous core droplets. This coalescence results in a substantial majority of the aqueous cores being comprised of a single aqueous core contained within the oil dispersion. By providing the water in oil in water emulsion having a single aqueous core, the release properties of the product incorporating the water in oil in water emulsion may be more easily and precisely controlled and modeled in a consistent manner.

[0044] Generally, the droplets formed (i.e., the first aqueous solution contained inside of the non-aqueous dispersion) will have a diameter of from about 1 micrometer to about 1000 micrometers, including from about 5 micrometers to about 500 micrometers, including from about 10 micrometers to about 500 micrometers, including from about 100 micrometers to about 250 micrometers. In some embodiments, the diameter of the droplets formed will be from about 10 micrometers to about 250 micrometers. In some

embodiments of the present disclosure, the single aqueous core will have a diameter of from about 5 micrometers to about 500 micrometers, including from about 10 micrometers to about 250 micrometers, including from about 10 micrometers to about 100 micrometers.

[0045] In some embodiments of the present disclosure, it may be desirable to reduce the size of the single aqueous core droplet of the double emulsion to (1) increase the concentration of the active agent or ingredient and increase potency and loading; and (2) provide a thicker protective layer of the oil phase surrounding the core, for the same total volume of oil used. When it is desirable to reduce the size of the single aqueous core droplet, this can be done by reversing the osmotic concentration difference between the continuous aqueous phase and the first aqueous solution (the single aqueous core droplet) through the addition of osmolytes to the continuous phase. By introducing osmolytes into the continuous phase, the osmotic swelling due to differences in osmotic concentrations as described above will be reduced and the size of single aqueous droplet will be reduced accordingly.

Preparation of Double-Walled Extended Release Microcapsules

[0046] In other embodiments of the present disclose, interfacial polymerization processes may be utilized to produce solid shell-liquid core extended release microcapsules having improved extended release benefits and profiles such that an active agent, such as a pesticide active agent, included in the inner aqueous core of the microcapsules may be delivered to a desired area (such as a field, or crop, or other area) and provide a desired protective benefit over an extended period of time such that the need for additional applications of the active agent are reduced or eliminated. In these embodiments, a double emulsion, such as a double emulsion described above, may be produced to include a separate and distinct polymer shell at both interfaces of the water in oil in water emulsion (that is, at both the Wl/O interface and the W2/0 interface) such that the active agent in the aqueous core is protected by two separate and distinct polymer layers to protect the active agent and further extend its release profile over time. Each polymer layer may have a thickness of from about 0.01 micrometers to about 10 micrometers. This protection allows the active agent to be substantially located in the inner aqueous core of the double emulsion such that the exchange of the active agent between the inner and outer aqueous phases is substantially reduced over time; that is, the active agent substantially remains in the inner aqueous phase over time.

[0047] Additionally, when colloidal particles are used in the preparation of the double emulsions as described above, they may be partially incorporated into the formed polymer shells and reinforce the polymer shells to increase their strength and further their protection profile over time. Further, particulate emulsion stabilizers may be less likely to exhibit undesirable interactions with the encapsulated active agent as compared to conventional emulsifiers resulting in a higher percentage of the active agent being capable of providing it intended benefit. [0048] In one suitable process for preparing a microcapsule having a first polymer shell, a second polymer shell, and an aqueous core, a first aqueous solution including a first water-soluble reactant for an interfacial polymerization reaction is emulsified into a nonaqueous dispersion comprising a first emulsion stabilizer. The emulsion may be prepared using conventional technology as described above. The first water-soluble reactant for an interfacial polymerization reaction may be any suitable reactant for initializing an interfacial polymerization at the interface of the water/oil emulsion. In some embodiments, the first water-soluble reactant for an interfacial polymerization reaction is hexamethylene diamine or other diamines or other triamines, oligo-amines, or polyamines, glycerol or other oligo-alcohols or polyols, and the like and combinations thereof.

[0049] The non-aqueous dispersion includes colloidal particles dispersed into a non-aqueous medium. The non-aqueous medium may be any suitable non-aqueous liquid suitable for forming the desired emulsion including for example, organic solvents such as trimethylolpropane trimethacrylate (TMPTMA), vegetable oils, mineral oils, and the like.

[0050] The colloidal particles present in the non-aqueous medium act to stabilize the double emulsion subsequently formed in the manufacturing process (and, as noted above, may also be incorporated into the polymeric shells to increase the strength thereof). The use of colloidal particles significantly reduces or eliminates the need for conventional monomeric and/or polymeric emulsifiers, although small amounts may be used in some embodiments. Suitable colloidal particles are known in the art and may include for example, hydrophobically modified inorganic particles such as silica particles, calcium carbonate or metal hydroxide particles, polymeric particles such as particles from cross- linked polymers (latex particles) or from oil-insoluble polymers or copolymers, modified microcrystalline cellulose, and the like and combinations thereof. In some embodiments, the colloidal particles may have an average diameter of from about 5 nanometers to about 2000 nanometers, including from about 7 nanometers to about 200 nanometers. Generally, the colloidal particles present in the non-aqueous dispersion will be present in an amount of from about 0.001wt.% to about 5.0wt.%, including from about 0.005wt% to about 0.5wt.%.

[0051] Once the water in oil emulsion is prepared, an oil-soluble reactant for triggering the formation of a first polymer shell at the interface of the water and oil emulsion is introduced into the emulsion and the resulting solution mixed using conventional mixing/emulsification processes as described herein for 1 second to about 1 minute or longer. Through interfacial polymerization at the interface of the water and oil a first polymer shell (sometimes referred to as a polymer skin) is formed that encapsulates the water droplets present in the non-aqueous dispersion to produce an oil-continuous capsule dispersion of aqueous core polymer capsule. Any oil-soluble reactant for triggering the formation of a first polymer shell is suitable for use in the present disclosure including, for example, polymethylene polyphenylpolyisocyanate, and other oligo- or polyisocyanates. Polyisocyanates may be used individually or as mixtures of two or more polyisocyanates. Suitable polyisocyanates are for example aliphatic isocyanates or aromatic isocyanates. These isocyanates may be present as monomeric or oligomeric isocyanates. The NCO content may be determined according to ASTM D 5155-96A.

Examples of suitable aliphatic diisocynates include tetramethylene diisocyanate, pentamethylene diisocyanate and hexamethylene diisocyanate as well as cycloaliphatic isocyanates, such as isophoronediisocyanate, 1 ,4-bisisocyanatocyclohexane and bis- (4isocyanato-cyclohexyl)methane. Suitable aromatic isocyanates include toluene diisocyanates (TDI: a mixture of the 2,4- and 2,6-isomers), diphenylmethene-4,4'- diisocyanate (MDI), polymethylene polyphenyl isocyanate, 2,4,4 '-diphenyl ether triisocyanate, 3,3 '-dimethyl-4,4' -diphenyl diisocyanate, 3,3'-dimethoxy-4,4'-diphenyl diisocyanate, 1,5-naphthylene diisocyanate and 4,4',4"-triphenylmethane triisocyanate. Also suitable are higher oligomers of the aforementioned diisocyanates such as the isocyanurates and biurethes of the aforementioned diisocyanates and mixtures thereof with the aforementioned diisocyanates. In another preferred embodiment, the polyisocyanate is an oligomeric isocyanate, preferably an aromatic, oligomeric isocyanate. Such oligomeric isocyanates may comprise above mentioned aliphatic diisocyanates and/or aromatic isocyanates in oligomerized form. The oligomeric isocyanates have an average

functionality in the range of 2.0 to 4.0, preferably 2.1 to 3.2, and more preferably 2.3 to 3.0. Typically, these oligomeric isocyanates have a viscosity (determined according to DIN 53018) in the range of from 20 to 1000 mPas, more preferably from 80 to 500 mPas and especially from 150 to 320 mPas. Such oligomeric isocyanates are commercially available for example from BASF SE under the tradenames Lupranat® M10, Lupranat® M20, Lupranat® M50, Lupranat® M70, Lupranat® M200, Lupranat® MM103, or from Bayer AG as Basonat®A270. [0052] The molar ratio of the first water soluble reactant to the oil-soluble reactant may be, for example, from about 1 :0.1 to about 1 : 10, including about 1 :2.4.

[0053] Once the oil-continuous capsule dispersion of aqueous core polymer capsule is formed, it is emulsified into a second aqueous solution comprising a second emulsion stabilizer to produce a water in oil in water emulsion. The emulsion stabilizer dispersed into the second aqueous solution may be the same as described above used in the non-aqueous dispersion. The water in oil in water emulsion is produced conventional mixing/emulsification processes as described herein.

[0054] Once the water in oil in water emulsion has been prepared, a second water- soluble reactant for an interfacial polymerization is introduced into the water in oil in water emulsion and the resulting mixture vortexed/mixed such that a second polymer shell is formed at the interface of the water/oil emulsion to produce the microcapsule. This second polymer shell is formed over a period of from about 1 hour to about 24 hours, including about 10 hours, generally at room temperature. Any water-soluble reactant for triggering the formation of a second polymer shell is suitable for use in the present disclosure including, for example, glycerol.

Pesticide Active Agent

[0055] As noted herein, the oil in water in oil emulsions described herein may include at least one active agent, including at least one pesticide active ingredient to provide a desired benefit upon application. Although described herein primarily in combination with a pesticide active agent, other active agents as are known to those of ordinary skill in the art are also within the scope of the present disclosure. Suitable pesticide active ingredients include both substantially water-soluble (pesticide has a solubility in water of at least 10 g/L, preferably at least 25 g/L, and in particular at least 35 g/L) and substantially water-insoluble (pesticide has a solubility in water of up to 10 g/L, including up to 2 g/L, and in particular up to 0.5 g/L at 20C) pesticide active ingredients, although the pesticide active ingredient should be substantially or completely soluble in the non-ionic surfactant described herein such that there is no milling required of the pesticide active ingredient. Insecticide active ingredients are particularly preferred within the scope of the present disclosure. [0056] The term pesticides refers to at least one active substance selected from the group of the fungicides, insecticides, nematicides, herbicides, safeners, biopesticides and/or growth regulators. Preferred pesticides are fungicides, insecticides, herbicides and growth regulators. Especially preferred pesticides are herbicides. Mixtures of pesticides of two or more of the abovementioned classes may also be used. The skilled worker is familiar with such pesticides, which can be found, for example, in the Pesticide Manual, 16th Ed. (2013), The British Crop Protection Council, London. Suitable insecticides are insecticides from the class of the carbamates, organophosphates, organochlorine insecticides,

phenylpyrazoles, pyrethroids, neonicotinoids, spinosins, avermectins, milbemycins, juvenile hormone analogs, alkyl halides, organotin compounds nereistoxin analogs, benzoylureas, diacylhydrazines, METI acarizides, and insecticides such as chloropicrin, pymetrozin, flonicamid, clofentezin, hexythiazox, etoxazole, diafenthiuron, propargite, tetradifon, chlorofenapyr, DNOC, buprofezine, cyromazine, amitraz, hydramethylnon, acequinocyl, fluacrypyrim, rotenone, or their derivatives. Suitable fungicides are fungicides from the classes of dinitroanilines, allylamines, anilinopyrimidines, antibiotics, aromatic hydrocarbons, benzenesulfonamides, benzimidazoles, benzisothiazoles, benzophenones, benzothiadiazoles, benzotriazines, benzyl carbamates, carbamates, carboxamides, carboxylic acid diamides, chloronitriles cyanoacetamide oximes, cyanoimidazoles, cyclopropanecarboxamides, dicarboximides, dihydrodioxazines, dinitrophenyl crotonates, dithiocarbamates, dithiolanes, ethylphosphonates, ethylaminothiazolecarboxamides, guanidines, hydroxy-(2-amino)pyrimidines, hydroxyanilides, imidazoles, imidazolinones, inorganic substances, isobenzofuranones, methoxyacrylates, methoxycarbamates, morpholines, N phenylcarbamates, oxazolidinediones, oximinoacetates,

oximinoacetamides, peptidylpyrimidine nucleosides, phenylacetamides, phenylamides, phenylpyrroles, phenylureas, phosphonates, phosphorothiolates, phthalamic acids, phthalimides, piperazines, piperidines, propionamides, pyridazinones, pyridines, pyridinylmethylbenzamides, pyrimidinamines, pyrimidines, pyrimidinonehydrazones, pyrroloquinolinones, quinazolinones, quinolines, quinones, sulfamides, sulfamoyltriazoles, thiazolecarboxamides, thiocarbamates, thiophanates, thiophenecarboxamides, toluamides, triphenyltin compounds, triazines, triazoles. Suitable herbicides are herbicides from the classes of the acetamides, amides, aryloxyphenoxypropionates, benzamides, benzofuran, benzoic acids, benzothiadiazinones, bipyridylium, carbamates, chloroacetamides, chlorocarboxylic acids, cyclohexanediones, dinitroanilines, dinitrophenol, diphenyl ether, glycines, imidazolinones, isoxazoles, isoxazolidinones, nitriles, N-phenylphthalimides, oxadiazoles, oxazolidinediones, oxyacetamides, phenoxycarboxylic acids,

phenylcarbamates, phenylpyrazoles, phenylpyrazolines, phenylpyridazines, phosphinic acids, phosphoroamidates, phosphorodithioates, phthalamates, pyrazoles, pyridazinones, pyridines, pyridinecarboxylic acids, pyridinecarboxamides, pyrimidinediones, pyrimidinyl(thio)benzoates, quinolinecarboxylic acids, semicarbazones,

sulfonylaminocarbonyltriazolinones, sulfonylureas, tetrazolinones, thiadiazoles, thiocarbamates, triazines, triazinones, triazoles, triazolinones, triazolocarboxamides, triazolopyrimidines, triketones, uracils, ureas.

[0057] The pesticide active ingredient may be present in the emulsions described herein in an amount of from about lwt.% to about 25wt.%, including from about 5wt.% to about 25wt.%, including from about 10wt.%> to about 25wt.%, including from about 10wt.%) to about 20wt.%>, including from about 15wt.% to about 20wt.%>. In one specific embodiment, the pesticide active ingredient may be present in the emulsion in an amount of about 20wt.%. In other specific embodiments, the pesticide active ingredient may be present in an amount of from about lwt.% to about 50wt.%, including from about 10wt.% to about 50wt.%>.

[0058] The disclosure furthermore relates to a method for controlling phytopathogenic fungi and/or undesired vegetation and/or undesired attack by insects or mites and/or for regulating the growth of plants, where the concentrate according to the invention or the emulsion according to the invention is allowed to act on the respective pests, their environment or on the crop plants to be protected from the respective pests, on the soil and/or on undesired plants and/or on the crop plants and/or their environment. In general, the therapeutic treatment of humans and animals is excluded from the method for controlling phytopathogenic fungi and/or undesired vegetation and/or undesired attack by insects or mites and/or for regulating the growth of plants.

[0059] When employed in crop protection, the application rates of the pesticides amount is from 0.001 to 2 kg per hectacre, preferably from 0.005 to 2 kg per hectacre, especially preferably from 0.05 to 0.9 kg per hectacre and in particular from 0.1 to 0.75 kg per hectacre, depending on the nature of the desired effect. In treatment of plant propagation materials such as seeds, e. g. by dusting, coating or drenching seed, amounts of active substance of from 0.1 to 1000 g, preferably from 1 to 1000 g, more preferably from 1 to 100 g and most preferably from 5 to 100 g, per 100 kg of plant propagation material (preferably seed) are generally required. When used in the protection of materials or stored products, the amount of active substance applied depends on the kind of application area and on the desired effect. Amounts customarily applied in the protection of materials are 0.001 g to 2 kg, preferably 0.005 g to 1 kg, of active substance per cubic meter of treated material.

[0060] Various types of oils, wetters, adjuvants, fertilizers or micronutrients and further pesticides (for example herbicides, insecticides, fungicides, growth regulators, safeners) may be added to the emulsion in the form of a premix or optionally only shortly before use (tank mix). These agents can be admixed to the compositions according to the disclosure at a weight ratio of from 1 : 100 to 100: 1, preferably from 1 : 10 to 10: 1.

[0061] The user applies the composition according to the disclosure usually from a predosage device, a knapsack sprayer, a spray tank, a spray plane, or an irrigation system. Usually, the agrochemical composition is made up with water, buffer, and/or further auxiliaries to the desired application concentration and the ready-to-use spray liquor or the agrochemical composition according to the disclosure is thus obtained. Usually, 20 to 2000 liters, preferably 50 to 400 liters, of the ready-to-use spray liquor are applied per hectare of agricultural useful area.

[0062] The present embodiments are to be considered in all respects as illustrative and not restrictive and that all changes and equivalents also come within the description of the present disclosure. The following non-limiting examples will further illustrate the improved double emulsions and methods of the present disclosure.

EXAMPLES

[0063] The following examples illustrate specific embodiments and/or features of water in oil in water double emulsion and processes of the present disclosure. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present disclosure, as many variations thereof are possible without departing from the spirit and scope of the disclosure.

Example 1

[0064] In this Example, a water in oil in water double emulsion including oil droplets having a single aqueous core droplet were prepared in accordance with the methods of the present disclosure.

[0065] Hydrophobically modified silica particles (Aerosil®R805 (Evonik)) (0.005wt.%) were dispersed into trimethylolpropane trimethacrylate (Sigma Aldrich) (0.75 mL). This dispersion (oil phase O) was mixed with a 5.0wt.% sodium chloride solution (0.375 mL) (water phase Wl) and homogenized for 10 seconds using a rotor-stator mixer (IKA T10 Ultra Turrax) set at 8000 rpm to produce a water in oil (Wl/O) emulsion.

[0066] An aqueous dispersion (W2) was prepared by dispersing hydrophilic silica particles (Aerosil®300 (Evonik)) (2wt.%) in deionized water (3.375 mL). The water in oil emulsion (Wl/O) was added to the aqueous dispersion (W2) and the resulting mixture was homogenized for 2 minutes using a variable speed vortex mixer (Vortex GENIE® SI-0276) at the maximum speed setting to prepare a water in oil in water (W1/0/W2) emulsion.

[0067] The resulting water in oil in water emulsion was transferred to a Petri dish and monitored with bright field microscopy wile osmotically driven swelling and coalescence of the aqueous core droplets proceeded. Figure 1 shows the droplets just after transfer to the Petri dish, and Figure 2 shows the droplets after one hour in the Petri dish. After about four hours the size of the aqueous core droplets did not change substantially. Figure 3 shows the double emulsion in its final state wherein the majority of the oil droplets include a single aqueous core droplet.

Example 2

[0068] In this Example, the double emulsion including predominantly single core droplets of Example 1 is further processed to reduce the size of the aqueous core droplets. To the double emulsion of Example 1 was added 2M (12wt.%) NaCl (3.375 mL) to initiate a pronounced de-swelling of the aqueous core droplets over the course of about 1 hour. Figure 4 shows the droplets at the time of addition of the NaCl solution, and Figure 5 shows the droplets after 1 hour of de-swelling wherein the single aqueous core size has been reduced significantly.

Example 3

[0069] In this Example, microcapsules having a first polymer shell, a second polymer shell, and an aqueous core were prepared in accordance with one embodiment of the present disclosure.

[0070] An aqueous solution (Wl) was prepared by combining deionized water (0.675 mL) with a 25wt.% solution of hexamethylene diamine (0.075 mL) and vortexing the mixture for 10 seconds using a variable speed vortex mixer at the maximum speed setting.

[0071] A non-aqueous dispersion (O) was prepared by dispersing hydrophobically modified silica particles (Aerosil® R805 (Evonik)) in trimethylolpropane trimethacrylate (1.5 mL) at a silica particle concentration of 2.0wt.%.

[0072] An aqueous solution (W2) was prepared by dispersing hydrophilic silica particles (Aerosil® 300 (Evonik)) in deionized water (6.75 mL) at a particle concentration of 7.0wt.%.

[0073] Aqueous solution Wl was emulsified in the non-aqueous dispersion (O) by homogenization for 10 seconds using a rotor-stator mixer set at 8000 rpm to prepare the Wl/O emulsion.

[0074] Polymethylene polyphenylpolyisocyanate was added to the Wl/O emulsion at a molar HMDA:polyisocyanate ratio of about 1 :2.4 to induce the formation of a polyuria skin at the Wl/O interface and the resulting emulsion was vortexed at maximum speed for 10 seconds.

[0075] The resulting Wl/O emulsion was then added to the aqueous dispersion W2 and emulsified by vortexing at maximum speed for 2 minutes to produce a W1/0/W2 emulsion. [0076] To this W1/0/W2 emulsion was added an aqueous 25wt.% solution of glycerol (0.75 mL) and the emulsion was vortexed one more time for 10 seconds at the maximum setting to induce polymerization of the second polymer layer.

[0077] After 12 hours at room temperature the formation of a polyurethane skin at the 0/W2 interface was complete and the microcapsules having two polymer layers and an aqueous core was complete.

Example 4

[0078] In this Example, microcapsules having a first polymer shell, a second polymer shell, and an aqueous core including a pesticide active ingredient were prepared in accordance with one embodiment of the present disclosure and evaluated for encapsulation efficiency.

[0079] An aqueous solution Wl was prepared by combining 0.675 mL of an aqueous solution containing 324 mg of the pesticide active ingredient 3,6-dichloro-o-anisic acid with 0.075 mL of a 25wt.% aqueous solution of hexamethylene diamine and vortexing the mixture for 10 seconds using a variable speed vortex mixer at the maximum speed setting.

[0080] A non-aqueous dispersion (O) was prepared by dispersing hydrophobically modified silica particles (Aerosil® R805 (Evonik)) in trimethylolpropane trimethacrylate (1.5 mL) at a silica particle concentration of 2.0wt.%.

[0081] An aqueous solution (W2) was prepared by dispersing hydrophilic silica particles (Aerosil® 300 (Evonik)) in deionized water (6.75 mL) at a particle concentration of 7.0wt.%.

[0082] Aqueous solution Wl was emulsified in the non-aqueous dispersion (O) by homogenization for 10 seconds using a rotor-stator mixer set at 8000 rpm to prepare the Wl/O emulsion.

[0083] Polymethylene polyphenylpolyisocyanate was added to the Wl/O emulsion at a molar HMDA:polyisocyanate ratio of about 1 :2.4 to induce the formation of a polyuria skin at the Wl/O interface and the resulting emulsion was vortexed at maximum speed for 10 seconds.

[0084] The resulting Wl/O emulsion was then added to the aqueous dispersion W2 and emulsified by vortexing at maximum speed for 2 minutes to produce a W1/0/W2 emulsion.

[0085] To this W1/0/W2 emulsion was added an aqueous 25wt.% solution of glycerol (0.75 mL) and the emulsion was vortexed one more time for 10 seconds at the maximum setting to induce polymerization of the second polymer layer.

[0086] After 12 hours at room temperature the formation of a polyurethane skin at the 0/W2 interface was complete and the microcapsules having two polymer layers and an aqueous core was complete.

[0087] The microcapsules were then diluted with deionized water (30 mL), briefly hand shaken, vortexed at the maximum setting for 10 seconds and then centrifuged for 2 minutes at 3000 rpm. The amount of pesticide active ingredient in the supernatant was determined by high-performance liquid chromatography and found to be 20 mg, which corresponds to a loss of pesticide active ingredient of about 6wt.% which indicates that the microcapsules including two distinct polymer layers are highly efficient in protecting the encapsulated cargo.

Example 5

[0088] In this example, the microcapsules of Example 4 including the pesticide active agent were tested against a commercially available herbicide in a pre-emergence experiment.

[0089] The microcapsules of Example 4 and the commercially available herbicide were both used in an application rate of 1 kg/hectare, and the test weed was NAAOF (watercress). As shown in Figure 6, after four weeks, the extended residual activity of the Example 4 microcapsules was clearly observed (15% activity) whereas the commercially available herbicide had activity of zero.

Claims

WHAT IS CLAIMED IS:

1. A process for preparing a microcapsule having a first polymer shell, a second polymer shell, and an aqueous core, the process comprising: emulsifying a first aqueous solution comprising a first water-soluble reactant for an interfacial polymerization reaction in a non-aqueous dispersion comprising a first emulsion stabilizer to produce a water in oil emulsion; introducing an oil-soluble reactant into the water in oil emulsion and allowing the formation of a first polymer shell by interfacial polymerization at an interface of the water in oil emulsion to produce an oil-continuous capsule dispersion of aqueous core polymer capsule; emulsifying the oil-continuous capsule dispersion of aqueous core polymer capsule in a second aqueous solution comprising a second emulsion stabilizer to produce a water in oil in water emulsion; and introducing a second water-soluble reactant into the water in oil in water emulsion and allowing the formation of a second polymer shell by interfacial polymerization at an interface of the water in oil in water emulsion to produce the microcapsule.

2. The process of claim 1 further including introducing a pesticide active ingredient into the first aqueous solution prior to emulsifying the first aqueous solution in the non-aqueous solution.

3. The process of claim 2 wherein the pesticide active agent is a substantially soluble pesticide active agent that is solubilized in the first aqueous solution.

4. The process of claim 2 wherein the pesticide active agent is a substantially insoluble pesticide active agent that is dispersed in the first aqueous solution.

5. The process of claim 1 wherein at least one of the first emulsion stabilizer and the second emulsion stabilizer comprises colloidal particles.

6. The process of claim 5 wherein the colloidal particles are inorganic particles or polymeric (dispersion) particles.

7. The process of claim 1 wherein the first water-soluble reactant and the second water-soluble reactant is selected from the group consisting of hexamethylene diamine, diamines, triamines, glycerol, and combinations thereof.

8. The process of claim 1 wherein the oil-soluble reactant is polymethylene polyphenylpolyisocyanate.

9. The process of claim 1 wherein the molar ratio of the first water-soluble reactant to the oil-soluble reactant is from about 1 :0.1 to about 1 : 10.

10. The process of claim 9 wherein the molar ratio of the first water-soluble reactant to the oil-soluble reactant is about 1 :2.4.

11. An extended release microcapsule comprising a water in oil in water emulsion, a first polymer shell at a first water and oil interface and a second polymer shell at a second water and oil interface, wherein the emulsion includes at least one pesticide active ingredient in an inner aqueous core.

12. The extended release microcapsule of claim 11 wherein the at least one pesticide active agent is a substantially soluble pesticide active agent dissolved in the inner aqueous core.

13. The extended release microcapsule of claim 11 wherein the at least one pesticide active agent is a substantially insoluble pesticide active agent that is dispersed in the inner aqueous core.

14. The extended release microcapsule of claim 11 wherein the microcapsule has a diameter of from about 10 micrometers to about 1000 micrometers.

15. A method for controlling phytopathogenic fungi and/or undesired vegetation and/or undesired attack by insects or mites and/or for regulating the growth of plants, where the extruded pesticide granular composition of any of claims 11-19 is allowed to act on the respective pests, their environment or on the crop plants to be protected from the respective pests, on the soil and/or on undesired plants and/or on the crop plants and/or their environment.