CA2311192A1 - Encapsulation process using isocyanate moieties - Google Patents
Encapsulation process using isocyanate moieties Download PDFInfo
- Publication number
- CA2311192A1 CA2311192A1 CA 2311192 CA2311192A CA2311192A1 CA 2311192 A1 CA2311192 A1 CA 2311192A1 CA 2311192 CA2311192 CA 2311192 CA 2311192 A CA2311192 A CA 2311192A CA 2311192 A1 CA2311192 A1 CA 2311192A1
- Authority
- CA
- Canada
- Prior art keywords
- moieties
- liquid
- microcapsules
- anhydride
- reactants
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
- B01J13/16—Interfacial polymerisation
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/26—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests in coated particulate form
- A01N25/28—Microcapsules or nanocapsules
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Plant Pathology (AREA)
- Toxicology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Abstract
The invention provides a method of forming microcapsules or particles of a matrix which comprises dispersing a first liquid in a second, immiscible or partially miscible liquid that forms a continuous phase, one liquid containing reactants bearing (a) isocyanate moieties and (b) anhydride moieties, glycidyl moieties or electrophilic moieties bearing base-susceptible leaving groups and the other liquid containing a reactant that bears reactive groups that will react with the reactants in the said one liquid to form a membrane. The microcapsules or particles can encapsulate material that will undergo slow release. The invention also extends to the formed microcapsules or particles.
Description
'69641-12 The present invention relates to microcapsules and to particles of a matrix, to methods of making them, and to their use.
Background of the Invention Microcapsules and matrices containing an encapsulated active ingredient are known for many purposes. In some instances, slow release of the encapsulated ingredient is required. Materials that have been encapsulated in microcapsules and hydrogel matrices include pharmaceuticals, pesticides, fungicides, herbicides, bactericides, dyes, inks, chemical reagents and flavouring materials, and semiochemicals, that is materials that will modify the behaviour of animal species, for example pheromones.
In the area of crop protection, insect pheromones are proving to be a biorational alternative to conventional hard pesticides. In particular, attractant pheromones can be used effectively in controlling insect populations by disrupting the mating process. Here, small amounts of species-specific pheromone are dispersed over the area of interest during the mating season, raising the background level of pheromone to the point where the male insect cannot identify and follow the plume of attractant pheromone released by his female mate.
Mechanical dispensers, hollow fibres, impregnated plastic twist-ties, and polymer microcapsules are some of the delivery devices used to deliver the pheromone throughout the mating period of the insect, typically two to six weeks.
Polymer microcapsules, in particular, promise to serve as efficient delivery vehicles, as they: a) are easily prepared by a number of interfacial and precipitation polymerizations, b) enhance the resistance of the pheromone to oxidation and irradiation during storage and release, c) may in '69641-12 principle be tailored to control the rate of release of the pheromone fill, and (d) permit easy application of pheromones by, for example, spraying, using conventional spraying equipment.
One known method of forming pheromone-filled microcapsules involves dissolving pheromone and a diisocyanate in xylene and dispersing this solution into an aqueous solution containing a diamine. A polyurea membrane forms rapidly at the interface between the continuous aqueous phase and the dispersed xylene droplets, resulting in formation of microcapsules containing the pheromone and xylene; see for example PCT international application WO 98/45036, Li, Nielsen, Sengupta, published 15 October 1998. Although this method is useful and yields valuable products it does have some limitations. Isocyanates are highly reactive compounds and it is at times difficult to encapsulate compounds that react with the isocyanate. For example, it is difficult to encapsulate compounds containing hydroxyl groups such as alcohols.
Furthermore, isocyanates are relatively expensive compounds and must be handled with care.
The present invention provides an encapsulation method in which use of an isocyanate may be reduced.
Summary of the Invention In one aspect, the invention provides a method of forming microcapsules or particles of a matrix which comprises dispersing a first liquid in a second, immiscible or partially miscible liquid that forms a continuous phase, one liquid containing reactants bearing (a) isocyanate moieties and (b) anhydride moieties, glycidyl moieties, or electrophilic moieties bearing base-susceptible leaving groups (e.g. alkyl or aryl halides, tosylates, acid chlorides), and the other liquid . '69641-12 containing a reactant that bears reactive groups that will react with the reactants in the said one liquid to form a membrane.
If a material is to be encapsulated in the microcapsules or the particles of the matrix, that material is dissolved or dispersed in the first liquid that forms the dispersed phase. The invention is particularly useful for encapsulating materials for which controlled release is needed, for instance, insect pheromones.
In another aspect, the invention relates to microcapsules or particles of a matrix formed by reaction, at an interface, between reactants bearing (a) isocyanate moieties and (b) anhydride moieties, glycidyl moieties or electrophilic moieties bearing base-susceptible leaving groups, and a reactant that bears reactive groups that will react with the reactants bearing (a) and (b) to form a membrane.
As stated above, it is well known that isocyanates can be reacted with amines to form membranes encapsulating mterials, which will undergo controlled release. Until the present invention, however, it has not been known to use a combination of isocyanates and anhydride moieties, glycidyl moieties, or electrophilic moieties bearing base-susceptible leaving groups to form membranes for encapsulating materials.
As shown in the examples given below, addition of a styrene-malefic anhydride (SMA) copolymer to a given isocyanate formulation results in microcapsules having different controlled-release properties as compared with microcapsules formed from molecules bearing isocyanates alone.
For example, in an interfacial encapsulation experiment carried out at 20°C, the addition of 50$ by weight of '69641-12 SMA14 copolymer(14 mold malefic anhydride)to a polyisocyanate (Mondur MRS), in the presence of a five-fold excess of tetraethylenepentamine (TEPA), led to an increase in the rate of release of dodecyl acetate by a factor of approximately three in comparison to the microcapsules formed solely from isocyanate.
Further, encapsulations performed using the same proportions and types of microcapsule-forming molecules indicated above, but carried out at 70°C, led to a decrease in the rate of release of dodecyl acetate, indicating that the encapsulation temperature may be used as a way of varying the rate of release.
In both cases, the microcapsule walls consist of a combination of polyurea and SMA14-amine adduct, present in two distinct but interpenetrating phases. These composite microcapsules combine the high wall strength provided by the polyurea component, with the higher release rates provided by the SMA14-amine component.
The present invention makes available many different morphologies of microcapsules. Hence, the properties of the walls of the microcapsules can be adjusted to modify the rate of release of the encapsulated material.
Description of Preferred Embodiments To the extent that an anhydride moiety, glycidyl moiety, or an electrophilic moiety bearing a base-susceptible leaving group participates in reaction, it may replace an isocyanate moiety and may reduce the use made of the isocyanate. The molar ratio of isocyanate moieties (a) to anhydride moieties, glycidyl moieties, or electrophilic moieties bearing base-susceptible leaving groups (b) can vary over a wide range. It is possible to have a ratio of (a) to . 69641-12 (b) in the range 1:99 to 99:1, preferably 5:95 to 95:5, more preferably in the range 25:75 to 75:25. The chemical composition of the membrane will of course affect its properties, and the ratio of (a) to (b) can be selected to enhance particular properties. Often the amount of isocyanate is in the range 25~ to 75~, based on the total weight of (a) and (b) .
A reactant bearing isocyanate moieties (a) is a polyisocyanate such as a diisocyanate or a triisocyanate, or an oligomer. The polyisocyanate may be aromatic or aliphatic and may contain two, three or more isocyanate groups. Examples of aromatic polyisocyanates include 2,4- and 2,6-toluene diisocyanate, naphthalene diisocyanate, diphenylmethane diisocyanate and triphenylmethane-p,p',p"-trityl triisocyanate.
Aliphatic polyisocyanates may optionally be selected from aliphatic polyisocyanates containing two isocyanate functionalities, three isocyanate functionalities, or more than three isocyanate functionalities, or mixtures of these polyisocyanates. Preferably, the aliphatic polyisocyanate contains 5 to 30 carbons. More preferably, the aliphatic polyisocyanate comprises one or more cycloalkyl moieties.
Examples of preferred isocyanates include dicyclohexylmethane-4,4'-diisocyanate; hexamethylene 1,6-diisocyanate; isophorone diisocyanate; trimethyl-hexamethylene diisocyanate; trimer of hexamethylene 1,6-diisocyanate; trimer of isophorone diisocyanate; 1,4-cyclohexane diisocyanate; 1,4-(dimethyl-isocyanato) cyclohexane; biuret of hexamethylene diisocyanate;
urea of hexamethylene diisocyanate: trimethylenediisocyanate;
propylene-1,2-diisocyanate; and butylene-1,2-diisocyanate.
Mixtures of polyisocyanates can be used.
Particularly preferred polyisocyanates are polymethylene polyphenylisocyanates of formula:
Background of the Invention Microcapsules and matrices containing an encapsulated active ingredient are known for many purposes. In some instances, slow release of the encapsulated ingredient is required. Materials that have been encapsulated in microcapsules and hydrogel matrices include pharmaceuticals, pesticides, fungicides, herbicides, bactericides, dyes, inks, chemical reagents and flavouring materials, and semiochemicals, that is materials that will modify the behaviour of animal species, for example pheromones.
In the area of crop protection, insect pheromones are proving to be a biorational alternative to conventional hard pesticides. In particular, attractant pheromones can be used effectively in controlling insect populations by disrupting the mating process. Here, small amounts of species-specific pheromone are dispersed over the area of interest during the mating season, raising the background level of pheromone to the point where the male insect cannot identify and follow the plume of attractant pheromone released by his female mate.
Mechanical dispensers, hollow fibres, impregnated plastic twist-ties, and polymer microcapsules are some of the delivery devices used to deliver the pheromone throughout the mating period of the insect, typically two to six weeks.
Polymer microcapsules, in particular, promise to serve as efficient delivery vehicles, as they: a) are easily prepared by a number of interfacial and precipitation polymerizations, b) enhance the resistance of the pheromone to oxidation and irradiation during storage and release, c) may in '69641-12 principle be tailored to control the rate of release of the pheromone fill, and (d) permit easy application of pheromones by, for example, spraying, using conventional spraying equipment.
One known method of forming pheromone-filled microcapsules involves dissolving pheromone and a diisocyanate in xylene and dispersing this solution into an aqueous solution containing a diamine. A polyurea membrane forms rapidly at the interface between the continuous aqueous phase and the dispersed xylene droplets, resulting in formation of microcapsules containing the pheromone and xylene; see for example PCT international application WO 98/45036, Li, Nielsen, Sengupta, published 15 October 1998. Although this method is useful and yields valuable products it does have some limitations. Isocyanates are highly reactive compounds and it is at times difficult to encapsulate compounds that react with the isocyanate. For example, it is difficult to encapsulate compounds containing hydroxyl groups such as alcohols.
Furthermore, isocyanates are relatively expensive compounds and must be handled with care.
The present invention provides an encapsulation method in which use of an isocyanate may be reduced.
Summary of the Invention In one aspect, the invention provides a method of forming microcapsules or particles of a matrix which comprises dispersing a first liquid in a second, immiscible or partially miscible liquid that forms a continuous phase, one liquid containing reactants bearing (a) isocyanate moieties and (b) anhydride moieties, glycidyl moieties, or electrophilic moieties bearing base-susceptible leaving groups (e.g. alkyl or aryl halides, tosylates, acid chlorides), and the other liquid . '69641-12 containing a reactant that bears reactive groups that will react with the reactants in the said one liquid to form a membrane.
If a material is to be encapsulated in the microcapsules or the particles of the matrix, that material is dissolved or dispersed in the first liquid that forms the dispersed phase. The invention is particularly useful for encapsulating materials for which controlled release is needed, for instance, insect pheromones.
In another aspect, the invention relates to microcapsules or particles of a matrix formed by reaction, at an interface, between reactants bearing (a) isocyanate moieties and (b) anhydride moieties, glycidyl moieties or electrophilic moieties bearing base-susceptible leaving groups, and a reactant that bears reactive groups that will react with the reactants bearing (a) and (b) to form a membrane.
As stated above, it is well known that isocyanates can be reacted with amines to form membranes encapsulating mterials, which will undergo controlled release. Until the present invention, however, it has not been known to use a combination of isocyanates and anhydride moieties, glycidyl moieties, or electrophilic moieties bearing base-susceptible leaving groups to form membranes for encapsulating materials.
As shown in the examples given below, addition of a styrene-malefic anhydride (SMA) copolymer to a given isocyanate formulation results in microcapsules having different controlled-release properties as compared with microcapsules formed from molecules bearing isocyanates alone.
For example, in an interfacial encapsulation experiment carried out at 20°C, the addition of 50$ by weight of '69641-12 SMA14 copolymer(14 mold malefic anhydride)to a polyisocyanate (Mondur MRS), in the presence of a five-fold excess of tetraethylenepentamine (TEPA), led to an increase in the rate of release of dodecyl acetate by a factor of approximately three in comparison to the microcapsules formed solely from isocyanate.
Further, encapsulations performed using the same proportions and types of microcapsule-forming molecules indicated above, but carried out at 70°C, led to a decrease in the rate of release of dodecyl acetate, indicating that the encapsulation temperature may be used as a way of varying the rate of release.
In both cases, the microcapsule walls consist of a combination of polyurea and SMA14-amine adduct, present in two distinct but interpenetrating phases. These composite microcapsules combine the high wall strength provided by the polyurea component, with the higher release rates provided by the SMA14-amine component.
The present invention makes available many different morphologies of microcapsules. Hence, the properties of the walls of the microcapsules can be adjusted to modify the rate of release of the encapsulated material.
Description of Preferred Embodiments To the extent that an anhydride moiety, glycidyl moiety, or an electrophilic moiety bearing a base-susceptible leaving group participates in reaction, it may replace an isocyanate moiety and may reduce the use made of the isocyanate. The molar ratio of isocyanate moieties (a) to anhydride moieties, glycidyl moieties, or electrophilic moieties bearing base-susceptible leaving groups (b) can vary over a wide range. It is possible to have a ratio of (a) to . 69641-12 (b) in the range 1:99 to 99:1, preferably 5:95 to 95:5, more preferably in the range 25:75 to 75:25. The chemical composition of the membrane will of course affect its properties, and the ratio of (a) to (b) can be selected to enhance particular properties. Often the amount of isocyanate is in the range 25~ to 75~, based on the total weight of (a) and (b) .
A reactant bearing isocyanate moieties (a) is a polyisocyanate such as a diisocyanate or a triisocyanate, or an oligomer. The polyisocyanate may be aromatic or aliphatic and may contain two, three or more isocyanate groups. Examples of aromatic polyisocyanates include 2,4- and 2,6-toluene diisocyanate, naphthalene diisocyanate, diphenylmethane diisocyanate and triphenylmethane-p,p',p"-trityl triisocyanate.
Aliphatic polyisocyanates may optionally be selected from aliphatic polyisocyanates containing two isocyanate functionalities, three isocyanate functionalities, or more than three isocyanate functionalities, or mixtures of these polyisocyanates. Preferably, the aliphatic polyisocyanate contains 5 to 30 carbons. More preferably, the aliphatic polyisocyanate comprises one or more cycloalkyl moieties.
Examples of preferred isocyanates include dicyclohexylmethane-4,4'-diisocyanate; hexamethylene 1,6-diisocyanate; isophorone diisocyanate; trimethyl-hexamethylene diisocyanate; trimer of hexamethylene 1,6-diisocyanate; trimer of isophorone diisocyanate; 1,4-cyclohexane diisocyanate; 1,4-(dimethyl-isocyanato) cyclohexane; biuret of hexamethylene diisocyanate;
urea of hexamethylene diisocyanate: trimethylenediisocyanate;
propylene-1,2-diisocyanate; and butylene-1,2-diisocyanate.
Mixtures of polyisocyanates can be used.
Particularly preferred polyisocyanates are polymethylene polyphenylisocyanates of formula:
CHZ ~ CHZ
OCN I I NCO
\ \ \\
NCO
n wherein n is 2 to 4. These compounds are available under the trade-mark Mondur-MRS.
As reactants complementary to isocyanate moieties there are mentioned polyols and polyamines. These are also reactants complementary to anhydride moieties, glycidyl moieties, and electrophilic moieties bearing base-susceptible leaving groups and are discussed further below.
In some preferred embodiments, use is made of an oligomer or a copolymer containing reactive anhydride moieties that can react with a polyamine or a polyol. Sources of anhydride moieties include anhydride-containing compounds that also contain double bonds that can undergo polymerisation, for example malefic anhydride, itaconic anhydride, citraconic(methylmaleic) anhydride, ethylmaleic anhydride, 1,2-cyclohexene-1,2-dicarboxylic acid anhydride and 1,2-cyclohexene-4,5-dicarboxylic acid anhydride, of which malefic anhydride is preferred.
Malefic anhydride undergoes homopolymerisation only with difficulty and it is possible only to form low molecular weight oligomers. Malefic anhydride dimer and malefic anhydride oligomer can be used as a reactant. Malefic anhydride does readily undergo copolymerisation with other monomers, for example styrene, provided that the molar ratio of styrene to malefic anhydride is 1:1 or greater. This permits at least one styrene moiety to be located between any two malefic anhydride moieties, and eliminates the difficulty that occurs when attempts are made to homopolymerize malefic anhydride. A
preferred reactant is a malefic anhydride-containing copolymer.
Styrene-malefic anhydride copolymers (SMA) are commercially available with malefic anhydride contents up to 50 molo. Any styrene-malefic anhydride copolymer can be used.
A styrene-malefic anhydride copolymer containing 50 mol°s malefic anhydride (SMA50) has more reactive moieties than one containing, say, only 32 mold or 14 mold malefic anhydride (SMA32 or SMA14), so it will form a membrane more quickly and the membrane will be more polar. The membrane formed with SMA50 will be hydrophilic and will trap some water in its shell. Membranes formed from copolymers with 32 mold and 14 mol$ malefic anhydride are less hydrophilic and more amphiphilic. The release properties of the capsule will depend i.a. upon the thickness and polarity of the membrane. By varying the amount of malefic anhydride in the copolymer it is possible to match the release properties of the membrane to the particular material to be released.
The solubility properties of the styrene-malefic anhydride copolymer will depend on the malefic anhydride contents of the copolymer. The solubility parameter of copolymer containing 50 mold malefic anhydride is 10.1 (cal/cm3)1i2, so the copolymer is soluble only in solvents with some degree of polarity, for instance ethyl acetate, methyl ethyl ketone, tetrahydrofuran, dichloromethane and butyronitrile. Copolymer with 5 mold malefic anhydride has a solubility parameter of 9.314 (cal/cm3)ii2 and is soluble in these solvents, but also soluble in non-polar solvents such as toluene and xylene which, because of their immiscibility in water, are particularly suitable for use as the dispersed liquid if the continuous phase is aqueous. Copolymer with 32 mold malefic anhydride has a solubility parameter of 9.907 (cal/cm3) ii2_ It is possible to use anhydride moieties in a copolymer that is prepared from an unsaturated co-polymerisable monomer other than styrene. For instance, there may be used as co-monomer a-methylstyrene, or styrene or a-methylstyrene that is substituted in the benzene ring of the styrene moiety. As substituent, mention is made of lower alkyl groups having up to 18 carbon atoms, preferably up to 6 carbon atoms. The extra alkyl substituents on, for example, p-methylstyrene and p-tert.-butylstyrene render the copolymer less polar and more soluble in the water-immiscible solvents such as xylene and toluene that are commonly preferred for use in interfacial reactions. Other possible unsaturated copolymerisable monomers that may be present, in place of or in addition to styrene, include olefins such as ethylene, conjugated dimes such as 1,3-butadiene and isoprene, alkyl acrylates and methacrylates, especially lower alkyl such as the methyl, ethyl and, preferably, the butyl and ethylhexyl esters, vinyl acetate, acrylonitrile, methacrylonitrile, acrylamides, methacrylamides and unsaturated ethers such as alkyl vinyl ethers, for instance, the methyl and ethyl ethers. Also mentioned are the vinyl sulphoxides and vinyl sulphones. Mixtures of these can be used in the copolymerization to design copolymers that have particular solubility properties and, when reacted with polyamine or polyol, impart particular properties to the membrane formed.
The molecular weight of the polymer may be greater than about 1,000, preferably greater than about 20,000. There is no critical upper limit on the molecular weight of the copolymer, provided that the viscosity does not increase to such an extent that reaction is impeded. Molecular weights greater than about 400,000 are not normaly used.
OCN I I NCO
\ \ \\
NCO
n wherein n is 2 to 4. These compounds are available under the trade-mark Mondur-MRS.
As reactants complementary to isocyanate moieties there are mentioned polyols and polyamines. These are also reactants complementary to anhydride moieties, glycidyl moieties, and electrophilic moieties bearing base-susceptible leaving groups and are discussed further below.
In some preferred embodiments, use is made of an oligomer or a copolymer containing reactive anhydride moieties that can react with a polyamine or a polyol. Sources of anhydride moieties include anhydride-containing compounds that also contain double bonds that can undergo polymerisation, for example malefic anhydride, itaconic anhydride, citraconic(methylmaleic) anhydride, ethylmaleic anhydride, 1,2-cyclohexene-1,2-dicarboxylic acid anhydride and 1,2-cyclohexene-4,5-dicarboxylic acid anhydride, of which malefic anhydride is preferred.
Malefic anhydride undergoes homopolymerisation only with difficulty and it is possible only to form low molecular weight oligomers. Malefic anhydride dimer and malefic anhydride oligomer can be used as a reactant. Malefic anhydride does readily undergo copolymerisation with other monomers, for example styrene, provided that the molar ratio of styrene to malefic anhydride is 1:1 or greater. This permits at least one styrene moiety to be located between any two malefic anhydride moieties, and eliminates the difficulty that occurs when attempts are made to homopolymerize malefic anhydride. A
preferred reactant is a malefic anhydride-containing copolymer.
Styrene-malefic anhydride copolymers (SMA) are commercially available with malefic anhydride contents up to 50 molo. Any styrene-malefic anhydride copolymer can be used.
A styrene-malefic anhydride copolymer containing 50 mol°s malefic anhydride (SMA50) has more reactive moieties than one containing, say, only 32 mold or 14 mold malefic anhydride (SMA32 or SMA14), so it will form a membrane more quickly and the membrane will be more polar. The membrane formed with SMA50 will be hydrophilic and will trap some water in its shell. Membranes formed from copolymers with 32 mold and 14 mol$ malefic anhydride are less hydrophilic and more amphiphilic. The release properties of the capsule will depend i.a. upon the thickness and polarity of the membrane. By varying the amount of malefic anhydride in the copolymer it is possible to match the release properties of the membrane to the particular material to be released.
The solubility properties of the styrene-malefic anhydride copolymer will depend on the malefic anhydride contents of the copolymer. The solubility parameter of copolymer containing 50 mold malefic anhydride is 10.1 (cal/cm3)1i2, so the copolymer is soluble only in solvents with some degree of polarity, for instance ethyl acetate, methyl ethyl ketone, tetrahydrofuran, dichloromethane and butyronitrile. Copolymer with 5 mold malefic anhydride has a solubility parameter of 9.314 (cal/cm3)ii2 and is soluble in these solvents, but also soluble in non-polar solvents such as toluene and xylene which, because of their immiscibility in water, are particularly suitable for use as the dispersed liquid if the continuous phase is aqueous. Copolymer with 32 mold malefic anhydride has a solubility parameter of 9.907 (cal/cm3) ii2_ It is possible to use anhydride moieties in a copolymer that is prepared from an unsaturated co-polymerisable monomer other than styrene. For instance, there may be used as co-monomer a-methylstyrene, or styrene or a-methylstyrene that is substituted in the benzene ring of the styrene moiety. As substituent, mention is made of lower alkyl groups having up to 18 carbon atoms, preferably up to 6 carbon atoms. The extra alkyl substituents on, for example, p-methylstyrene and p-tert.-butylstyrene render the copolymer less polar and more soluble in the water-immiscible solvents such as xylene and toluene that are commonly preferred for use in interfacial reactions. Other possible unsaturated copolymerisable monomers that may be present, in place of or in addition to styrene, include olefins such as ethylene, conjugated dimes such as 1,3-butadiene and isoprene, alkyl acrylates and methacrylates, especially lower alkyl such as the methyl, ethyl and, preferably, the butyl and ethylhexyl esters, vinyl acetate, acrylonitrile, methacrylonitrile, acrylamides, methacrylamides and unsaturated ethers such as alkyl vinyl ethers, for instance, the methyl and ethyl ethers. Also mentioned are the vinyl sulphoxides and vinyl sulphones. Mixtures of these can be used in the copolymerization to design copolymers that have particular solubility properties and, when reacted with polyamine or polyol, impart particular properties to the membrane formed.
The molecular weight of the polymer may be greater than about 1,000, preferably greater than about 20,000. There is no critical upper limit on the molecular weight of the copolymer, provided that the viscosity does not increase to such an extent that reaction is impeded. Molecular weights greater than about 400,000 are not normaly used.
There can be used polymers bearing pendant glycidyl moieties. These polymers can be formed by copolymerizing glycidyl acrylate or methacrylate with styrene or any of the other copolymerizable monomers mentioned above. The reaction of glycidyl moieties can again be catalysed by a tertiary amine that is dissolved in the continuous aqueous phase.
There can be used polymers that include electrophilic moieties bearing a base-susceptible leaving group. An example is a polymer bearing chloromethyl moieties, where the chlorine serves as the leaving group. Chloromethylstyrene can be copolymerized with any of the copolymerizable monomers discussed above.
Suitable reactants that will react with isocyanates and with anhydride moieties, glycidyl moieties, and electrophilic moieties bearing base-susceptible leaving groups include water-soluble primary and secondary polyamines, preferably primary diamines. These include diamines of formula (I) H2N (CH2)n NH2 (I) wherein n is an integer from 2 to 10, preferably 2 to 6.
Mention is made of hexamethylenediamine. Also suitable are mixed primary/secondary amines, and mixed primary/secondary/tertiary amines. Mixed primary/secondary amines include those of Formula (II):
R R
H2N ( CH2CHNH )m CH2CHNH2 ( II ) wherein m is an integer from 1 to 1,000, preferably 1 to 10 and R is hydrogen or a methyl or ethyl group. Mention is made of TEPA. Suitable primary/secondary/tertiary amines include compounds like those of formula (II) but modified in that one or more of the hydrogen atoms attached to a non-terminal nitrogen atom of the compound of formula (II) is replaced by a lower aminoalkyl group such as an aminoethyl group. The commercial product of tetraethylenepentamine usually contains some isomers branched at non-terminal nitrogen atoms, so that the molecule contains one or more tertiary amino groups. All these polyamines are readily soluble in water, which is suitably used as the second continuous phase. Other suitable polyamine reactants include polyvinylamine, polyethyleneimine, and polyallylamine. Primary and secondary amino groups will react with anhydride moieties. Tertiary amino groups catalyse the reaction of the primary and secondary amino groups.
Also suitable are polyetheramines of general formula (III) R R
H2N ( CH2CH0 ) r ( CH2CH ) NH2 ( III ) where r is an integer from 1 to 20, preferably 2 to 15, more preferably 2 to 10, and R is hydrogen, methyl or ethyl. Such compounds are available under the trademark Jeffamine from Huntsman.
If a reactant is an amine it must contain at least two amino groups capable of reacting with moieties (a) and (b), i.e., at least two groups that are primary or secondary amino groups. Hence, the compound must be, at least, a diamine, but it may contain more than two amino groups; see for example compounds of formula (II). In this specification the term "diamine" is used to indicate a compound that has at least two reactive amino groups, but the term does not necessarily exclude reactants that contain more than two amino groups.
Similar remarks apply to the term "diol".
Reactants that will react with isocyanates, anhydride moieties, glycidyl moieties, and electrophilic moieties bearing base-susceptible leaving groups also include compounds that contain both amino and hydroxyl groups. As examples of such compounds there are mentioned monoethanolamine, diethanolamine, triethanolamine, dialkylethanolamines, N-alkyl-diethanolamines and N,N-dimethyl-2-amino(ethoxy)ethanol.
The reaction between malefic anhydride and diamine, results in the opening of the anhydride ring with the formation of one amide moiety and one ammonium salt moiety between a carboxyl group and an amine. Hence, the membrane formed is, in part, ionic. It is possible to subject this product to elevated temperature to dehydrate it to form a maleimide.
If a material is to be encapsulated in the microcapsules formed, that material is dissolved or dispersed in the solution in the first liquid, together with the reactants comprising the isocyanate and anhydride moieties, glycidyl moieties or electrophilic moieties bearing base-susceptible leaving groups. As indicated above, this material must not be so reactive with the isocyanate or anhydride that it competes significantly with the reaction that creates the membrane. Alcohols can be encapsulated, provided that the isocyanate content of the reactants is low. Although alcohols will react with anhydride moieties to form acid esters and with isocyanate moieties to form urethanes, these reactions are slow, compared with the reactions between the isocyanate moiety or the anhydride moiety and the amine, so these reactions do not compete significantly with the desired membrane-forming reactions. As stated above, the rate of the membrane-forming reaction depends on the particular first liquid that is used as the dispersed organic phase. A catalyst can be incorporated with the amine in the aqueous phase to speed the membrane-forming reactions. Suitable catalysts include tertiary amines.
The tertiary amine, in the amount used, should be freely soluble in the water present in the reaction mixture.
The simplest tertiary amine is trimethylamine and this compound, and its C2, C3 and C4 homologues can be used. It is of course possible to use tertiary amines containing a mixture of alkyl groups, for instance methyldiethylamine. The tertiary amine can contain more than one tertiary amine moiety. It may also contain other functional groups provided that those other functional groups do not interfere with the required reaction, or the functional groups participate beneficially in the required reaction. As an example of a functional group that does not interfere there is mentioned an ether group. As examples of groups that participate there are mentioned primary and secondary amino groups, and hydroxyl groups. Examples of suitable tertiary amines include compounds of the following structures:
N[C H2(C H2~ ~ Hg~3 ~ where n is 0, 1, 2 or 3 n C H3~
CH3\ /C H3 /N-C HZC H2-N~
CH3-N~CH2CH20CH2CH20H
and Of the tertiary amines triethylamine (TEA) is preferred.
The amount of the tertiary amine required is not very great. It is conveniently added in the form of a solution containing 0.5g of TEA per lOmL of water. Usually 0.5% by weight of this solution, based on the total weight, suffices, although 0.7% may be required in some cases. The amount used does not usually exceed 1%, although no disadvantage arises if more than 1% is used.
Catalysts other than tertiary amines can be used.
Metal salts that are soluble in an organic solvent used as the first liquid can be used. Mention is made of titanium tetraalkoxides available under the trademark Tyzor from DuPont and stannous octanoate, although these should not be used when there is also present in the organic solvent an alcohol to be encapsulated.
The ability to encapsulate alcohols is of particular significance. The pheromone of the codling moth is E,E-8,10-C12 alcohol and it has been difficult to encapsulate this pheromone by the previously known technique involving isocyanate. The present invention permits encapsulation of alcoholic compounds, including alcoholic pheromones and should permit encapsulation of codling moth pheromone, provided that the isocyanate content of the reactants is low.
In other embodiments of the invention it is possible to react the molecules (a) and (b) with a polyol, rather than a polyamine. Suitable polyols include diols of formula (IV):
HO (CH2)n OH (IV) wherein n is an integer from 2 to 10, preferably 2 to 4, and of formula (V):
R R (V) HO ( CHZCHO )m CH2CHOH
wherein m is an integer from 1 to 10 and R is hydrogen or a methyl or ethyl group. The reactions between molecules (a) and (b) and an alcohol are slower than the reactions between molecules (a) and (b) and an amine. A catalyst can be used and suitable catalysts include the tertiary amines and other catalysts mentioned above. It should be possible to encapsulate an alcohol by means of reactions between isocyanate moieties and anhydride moieties, glycidyl moieties or elecrophilic moieties bearing base-susceptible leaving and a diol. Reaction between anhydride moieties, for instance, and hydroxyl groups of the diol, in aqueous solution, should occur much more quickly than reaction between anhydride moieties and a hydroxyl group in organic solvent. This is particularly so if the aqueous solution contains a water-sol~Zble catalyst for the reaction, for instance a tertiary amine that reacts with the anhydride moiety to release an ionised moiety, which is drawn to the aqueous/organic interface.
The first liquid, that serves as the dispersed phase, is a liquid in which the first reactant can be dispersed or dissolved and in which any material to be encapsulated can be dispersed or dissolved. It should be immiscible, or at least only partially miscible, with the second liquid. While the limits on what is meant by "partially miscible" are not precise, in general a substance is considered to be water-immiscible if its solubility in water is less than about 0.5~
by weight. It is considered to be water-soluble if its solubility is greater than 98~, i.e., if 1 gram of the substance is put in 100 grams of water, 0.98 gram would dissolve. A substance whose solubility falls between these approximate limits is considered to be partially water-miscible. Desirably, the first liquid is a marginal solvent for the polymer reactant, and has a boiling point in the vicinity of 100°C. The properties of the first liquid, which will become encapsulated with the active material that is to be released, will affect the rate of release of that active material. Selection of a first liquid has to be made with these considerations in mind. Suitable candidates for use as the first liquid include alkylbenzenes such as toluene, xylene, ethers such as methyl tert.-butyl ether, ketones such as methylisobutylketone, esters such as ethyl acetate, propyl acetate, halogenated aliphatic hydrocarbons such as dichloromethane, and aliphatic nitriles such as butyronitrile.
Mixtures of solvents can be used. There can also be used co-solvents to change the properties of solvents or solvent mixtures. As co-solvents there are mentioned aliphatic liquids such as kerosene and also cyclic hydrocarbons such as cyclohexane. For instance, styrene-malefic anhydride copolymer containing 14% malefic anhydride is soluble in all of these solvents, whereas copolymer containing 50~ malefic anhydride is soluble only in ethylacetate, dichloromethane and butyronitrile.
The second liquid that forms the continuous phase is preferably water or an aqueous solution with water as the major component, or another polar solvent.
Surfactants and emulsifiers can be used to assist in dispersion of the first liquid, i.e. the oil phase, in the second liquid. Mention is made of poly(vinylalcohol), polyvinylpyrrolidones and nonylphenyl-oligo-ethylene glycol, available under the trademark IGEPAL. These are of formula:
HO(C H2C H20) n CgH19 where n has an average value from about 9 to about 13.
IGEPAL 630, indicating a molecular weight of about 630, is mentioned. IGEPAL 630 is preferred to poly(vinylalcohol) as it results in smaller microcapsules. Other suitable surfactants and emulsifiers include polyethyleneglycol alkyl ethers, for example C18H35 (OCH2CH2) nOH, where n has an approximate value of about 20, available under the trade-mark BRIJ 98.
Ionic surfactants can be used. Sodium dodecyl sulphate (SDS) is mentioned as an example of an anionic surfactant.
The first liquid can be dispersed in the second liquid by dropping the first liquid into a stirred bath of the second liquid. The first liquid then forms droplets throughout the continuous phase of the second liquid. The second reactant may be present in the second liquid before the first liquid is added. In an alternative embodiment, the second reactant is not present in the second liquid when the first liquid has been dispersed, but is added subsequently. In any event, the first and second reactants meet and react at the interface between the continuous and dispersed phases, that is, the surface of the droplets, and react to form the membrane.
The membrane-forming reaction can be carried out at a temperature above 0°C, at room temperature or at elevated temperature. If elevated temperature is used, the optimum temperature will depend on the boiling point of each of the solvents that make up the dispersed and continuous phases and that of the material to be encapsulated. No advantage is seen in using a temperature greater than about 70°C.
The concentration of each reactant in the liquid will affect the properties of the product. At low concentrations, the formed membranes will be thinner than at higher concentrations. It is preferred that the concentration of the moieties (a) plus (b) is not less than about 2%, and good results have been achieved with concentrations of 5-6%. If the concentration of moieties (a) plus (b) in the first liquid is up to about 10% there will probably be formed discrete microcapsules. At yet higher concentrations, discrete microcapsules are not formed but rather matrix particles in which the first liquid is entrapped. If the concentration is greater than about 15%, there will probably be formed a matrix.
It is a matter of routine experimentation not involving exercise of any inventive faculty to determine at which concentrations a particular system yields microcapsules and at which concentrations it yields a matrix. The malefic anhydride content of an SMA copolymer will affect the nature of the matrix. With SMA50 the membrane formed will tend to be more hydrophilic and the matrix may be a hydrogel. With a copolymer of lower malefic anhydride content, say SMA14, the membrane formed is amphiphilic rather than hydrophilic.
When microcapsules are formed from a first liquid having a density less than that of water, they float on top of the liquid present. They can be shipped in this form, or scooped off. When particles of a hydrogel matrix are formed, the liquid can be decanted from the porous solid matrix particles.
As examples of materials to be encapsulated, particular mention is made of insect pheromones. In the notation used below to describe the structure of the pheromones, the type (E or Z) and position of the double bond or bonds are given first, the number of carbon atoms in the chain is given next and the nature of the end group is given last. To illustrate, the pheromone Z-10 C19 aldehyde has the structure;
HOC-C~H 0 CH3(CH2)i \(CH2)8CH
Pheromones may in fact be mixtures of compounds with one component of the mixture predominating, or at least being a significant component. Mentioned as examples of significant or predominant components of insect pheromones, with the target species in brackets, are the following: E/Z-11 C14 aldehyde (Eastern Spruce Budworm), Z-10 C19 aldehyde (Yellow Headed Spruce Sawfly), Z-11 C14 acetate (Oblique Banded Leafroller), Z-8 C12 acetate (Oriental Fruit moth) and E,E-8,10 C12 alcohol (Codling moth).
An example of a ketone that is a pheromone is E or Z
7-tetradecen-2-one, which is effective with the oriental beetle. An ether that is not a pheromone but is of value is 4-allylanisole, which can be used to render pine trees unattractive to the Southern pine beetle.
In one preferred embodiment, the product of the microencapsulation process is a plurality of microcapsules having a size in the range of from about 1 to about 5000 ~,un, preferably 20 Eun to 2000 Eun. Particularly preferred microcapsules have sizes in the range from about 10 ~,un to about 60 Etm, more preferably about 20 to about 30 Vim, and an encapsulated pheromone contained within the membrane. The microcapsules can be used in suspension in water to give a suspension suitable for aerial spraying. The suspension may contain a suspending agent, for instance a gum suspending agent such as guar gum, rhamsan gum or xanthan gum.
Incorporation of a light stabilizer, if needed to protect encapsulated material, is within the scope of the invention. Suitable light stabilizers include the tertiary phenylene diamine compounds disclosed in Canadian Patent No.
1,179,682, the disclosure of which is incorporated by reference. The light stabilizer can be incorporated by dissolving it, with the pheromone, in the oil phase.
Antioxidants and UV absorbers can also be incorporated. Many hindered phenols are known for this purpose. Mention is made of antioxidants available from Ciba-Geigy under the trade-marks Irganox 1010 and 1076. As UV absorbers there are mentioned Tinuvin 292, 400, 123 and 323 available from Ciba-Geigy.
To assist in determining the distribution of sprayed microcapsules it is possible to include a coloured dye or pigment in the microcapsules. The dye should be oil-soluble and can be incorporated, with the pheromone, in the oil phase.
It will be used only in a small amount and will not significantly affect the membrane-forming reaction.
Alternatively, or additionally, an oil-soluble or oil-dispersible dye can be included in the aqueous suspension of microcapsules, where it is absorbed by the microcapsule shell.
Suitable oil-soluble or oil-dispersible dyes can be obtained from DayGlo Color Corporation, Cleveland, Ohio, and include Blaze Orange, Saturn Yellow, Aurora Pink, and the like.
Although the invention has been described largely with reference to encapsulation of pheromones, other molecules that are active in nature can be encapsulated in a similar manner. As examples there are mentioned linalool, terpineol, fenchone, and keto-decenoic acids and hydroxy-decenoic acids, which encourage activity of worker bees. Encapsulated 4-allylanisole can be used to make pine trees unattractive to the Southern pine beetle. Encapsulated 7,8-epoxy-2-methyloctadecane can be used to combat the nun moth or the gypsy moth. Natural flavours and fragrances can be encapsulated. All these applications, and microcapsules containing these materials, are within the scope of the present invention.
Other compounds of interest for encapsulation include mercaptans. Some animals mark territory by means of urine, to discourage other animals from entering that territory.
Examples of such animals include preying animals such as wolves, lions, dogs, etc. Ingredients in the urine of such animals include mercaptans. By dispersing microcapsules containing the appropriate mercaptans it is possible to define a territory and discourage particular animals from entering that territory. For example, the urine of a wolf includes a mercaptan, and distribution of microcapsules from which this mercaptan is gradually released to define a territory will discourage deer from entering that territory. Other materials that can be encapsulated and used to discourage approach of animals include essences of garlic, putrescent eggs and capsaicin.
Other compounds that can be included in the microcapsules of the invention include perfumes, pharmaceuticals, fragrances, flavouring agents and the like.
It is also possible to encapsulate materials for uses other than in nature. Mention is made of dyes, inks, adhesives and reactive materials that must be contained until they are to be used, for instance, by controlled release from a microcapsule or by rupture of a microcapsule.
Other materials that can be encapsulated are mentioned in PCT international application WO 98/45036 mentioned above, the disclosure of which is incorporated herein by reference.
The invention is further illustrated with reference to the accompanying drawings and the following non-limiting examples.
In some of the examples, dodecyl acetate was used as the material to be encapsulated and released. Dodecyl acetate is itself a component of the pheromone of many species, including the pod borer. Its properties also make it valuable as a mimic for other pheromones that contain ester moieties and are free of other active groups such as hydroxyl and aldehyde groups.
Figure 1 shows schematically an apparatus used in the examples;
Figures 2A, 2B, 2C 2D and 2E are optical photomicrographs of capsules produced by Example 1;
Figure 3 is an optical photomicrograph of microcapsules produced by Example 2;
Figure 4 is an optical photomicrograph of microcapsules produced by Example 3;
Figure 5 is a graphical illustration of release data of microcapsules produced by Examples lA and 1C.
Figure 6 is a graphical illustration of release data of microcapsules produced by Examples 1C and 2.
Example 1 The following experiments illustrate formation of microcapsules using a mixture of isocyanate and styrene-malefic anhydride copolymer as one of a pair of complementary reactants and tetraethylene pentamine as the other of the pair of reactants, using the apparatus shown schematically in Figure 1.
In each experiment the same aqueous phase and the same procedure were used. The copolymer was a styrene-malefic anhydride copolymer of 14~ malefic anhydride content, molecular weight 224,000, obtained from Aldrich. Distilled water containing 1.3s Igepal 630(30 ml) was stirred for 1-2 minutes and the first liquid, i.e., the oil phase was added.
Thereafter, 10 ml of dissolved water in which 2g of TEPA was distilled were added over 2-3 minutes. The procedure was carried out at room temperature.
As oil phase there were used 15 ml of an 11:4 mixture of p-xylene:dodecylacetate in which the following were dissolved:
(A) lg isocyanate (Mondur MRS), no SMA
(comparative);
(B) lg Mondur MRS plus 0.25g SMA14;
(C) lg Mondur MRS plus 0.5g SMA14~
(D) lg Mondur MRS plus lg SMA14; and (E) lg SMA14, no isocyanate (comparative).
Optical photomicrographs of the formed microcapsules and shown in Figures 2A, B, C, D and E.
Example 2 The procedure of the previous example was repeated with a mixture lg Mondur MRS and 0.5g SMA14 (224,000 mol. wt.), except that the reaction was carried out not at room temperature but at 70°C. The microcapsules formed are shown in Figure 3.
Example 3 The procedure of example 1 was repeated with a mixture of lg Mondur MRS and lg SMA14, except that as oil phase there was used l5 ml of an 11:4 mixture of ethyl acetate and dodecyl acetate. The microcapsules formed are shown in Figure 4.
Example 4 Release measurements were made on microcapsules prepared according to Examples lA, 1C and 2. An initial amount of 0.5 g was originally taken from each set of microcapsules.
The weight of each set of microcapsules was measured daily.
The weight of each set of microcapsules was expressed graphically as a percentage of the weight of the microcapsules on day one as a function of time in days. It can be seen from Figure 5 that the initial rate of release for polyurea-SMA14 microcapsules, prepared according to Example 1C, is approximately ten times greater than the rate of release from the polyurea capsules prepared according to Example lA. It can be seen from Figure 6 that the rate of release from capsules prepared according to Example 1C is approximately one order of magnitude greater than the rate of release from capsules prepared according to Example 2, that is, with the same formulation, but carried out at a temperature of 70°C. This release profile is suitable for pheromone-based insect mating control.
There can be used polymers that include electrophilic moieties bearing a base-susceptible leaving group. An example is a polymer bearing chloromethyl moieties, where the chlorine serves as the leaving group. Chloromethylstyrene can be copolymerized with any of the copolymerizable monomers discussed above.
Suitable reactants that will react with isocyanates and with anhydride moieties, glycidyl moieties, and electrophilic moieties bearing base-susceptible leaving groups include water-soluble primary and secondary polyamines, preferably primary diamines. These include diamines of formula (I) H2N (CH2)n NH2 (I) wherein n is an integer from 2 to 10, preferably 2 to 6.
Mention is made of hexamethylenediamine. Also suitable are mixed primary/secondary amines, and mixed primary/secondary/tertiary amines. Mixed primary/secondary amines include those of Formula (II):
R R
H2N ( CH2CHNH )m CH2CHNH2 ( II ) wherein m is an integer from 1 to 1,000, preferably 1 to 10 and R is hydrogen or a methyl or ethyl group. Mention is made of TEPA. Suitable primary/secondary/tertiary amines include compounds like those of formula (II) but modified in that one or more of the hydrogen atoms attached to a non-terminal nitrogen atom of the compound of formula (II) is replaced by a lower aminoalkyl group such as an aminoethyl group. The commercial product of tetraethylenepentamine usually contains some isomers branched at non-terminal nitrogen atoms, so that the molecule contains one or more tertiary amino groups. All these polyamines are readily soluble in water, which is suitably used as the second continuous phase. Other suitable polyamine reactants include polyvinylamine, polyethyleneimine, and polyallylamine. Primary and secondary amino groups will react with anhydride moieties. Tertiary amino groups catalyse the reaction of the primary and secondary amino groups.
Also suitable are polyetheramines of general formula (III) R R
H2N ( CH2CH0 ) r ( CH2CH ) NH2 ( III ) where r is an integer from 1 to 20, preferably 2 to 15, more preferably 2 to 10, and R is hydrogen, methyl or ethyl. Such compounds are available under the trademark Jeffamine from Huntsman.
If a reactant is an amine it must contain at least two amino groups capable of reacting with moieties (a) and (b), i.e., at least two groups that are primary or secondary amino groups. Hence, the compound must be, at least, a diamine, but it may contain more than two amino groups; see for example compounds of formula (II). In this specification the term "diamine" is used to indicate a compound that has at least two reactive amino groups, but the term does not necessarily exclude reactants that contain more than two amino groups.
Similar remarks apply to the term "diol".
Reactants that will react with isocyanates, anhydride moieties, glycidyl moieties, and electrophilic moieties bearing base-susceptible leaving groups also include compounds that contain both amino and hydroxyl groups. As examples of such compounds there are mentioned monoethanolamine, diethanolamine, triethanolamine, dialkylethanolamines, N-alkyl-diethanolamines and N,N-dimethyl-2-amino(ethoxy)ethanol.
The reaction between malefic anhydride and diamine, results in the opening of the anhydride ring with the formation of one amide moiety and one ammonium salt moiety between a carboxyl group and an amine. Hence, the membrane formed is, in part, ionic. It is possible to subject this product to elevated temperature to dehydrate it to form a maleimide.
If a material is to be encapsulated in the microcapsules formed, that material is dissolved or dispersed in the solution in the first liquid, together with the reactants comprising the isocyanate and anhydride moieties, glycidyl moieties or electrophilic moieties bearing base-susceptible leaving groups. As indicated above, this material must not be so reactive with the isocyanate or anhydride that it competes significantly with the reaction that creates the membrane. Alcohols can be encapsulated, provided that the isocyanate content of the reactants is low. Although alcohols will react with anhydride moieties to form acid esters and with isocyanate moieties to form urethanes, these reactions are slow, compared with the reactions between the isocyanate moiety or the anhydride moiety and the amine, so these reactions do not compete significantly with the desired membrane-forming reactions. As stated above, the rate of the membrane-forming reaction depends on the particular first liquid that is used as the dispersed organic phase. A catalyst can be incorporated with the amine in the aqueous phase to speed the membrane-forming reactions. Suitable catalysts include tertiary amines.
The tertiary amine, in the amount used, should be freely soluble in the water present in the reaction mixture.
The simplest tertiary amine is trimethylamine and this compound, and its C2, C3 and C4 homologues can be used. It is of course possible to use tertiary amines containing a mixture of alkyl groups, for instance methyldiethylamine. The tertiary amine can contain more than one tertiary amine moiety. It may also contain other functional groups provided that those other functional groups do not interfere with the required reaction, or the functional groups participate beneficially in the required reaction. As an example of a functional group that does not interfere there is mentioned an ether group. As examples of groups that participate there are mentioned primary and secondary amino groups, and hydroxyl groups. Examples of suitable tertiary amines include compounds of the following structures:
N[C H2(C H2~ ~ Hg~3 ~ where n is 0, 1, 2 or 3 n C H3~
CH3\ /C H3 /N-C HZC H2-N~
CH3-N~CH2CH20CH2CH20H
and Of the tertiary amines triethylamine (TEA) is preferred.
The amount of the tertiary amine required is not very great. It is conveniently added in the form of a solution containing 0.5g of TEA per lOmL of water. Usually 0.5% by weight of this solution, based on the total weight, suffices, although 0.7% may be required in some cases. The amount used does not usually exceed 1%, although no disadvantage arises if more than 1% is used.
Catalysts other than tertiary amines can be used.
Metal salts that are soluble in an organic solvent used as the first liquid can be used. Mention is made of titanium tetraalkoxides available under the trademark Tyzor from DuPont and stannous octanoate, although these should not be used when there is also present in the organic solvent an alcohol to be encapsulated.
The ability to encapsulate alcohols is of particular significance. The pheromone of the codling moth is E,E-8,10-C12 alcohol and it has been difficult to encapsulate this pheromone by the previously known technique involving isocyanate. The present invention permits encapsulation of alcoholic compounds, including alcoholic pheromones and should permit encapsulation of codling moth pheromone, provided that the isocyanate content of the reactants is low.
In other embodiments of the invention it is possible to react the molecules (a) and (b) with a polyol, rather than a polyamine. Suitable polyols include diols of formula (IV):
HO (CH2)n OH (IV) wherein n is an integer from 2 to 10, preferably 2 to 4, and of formula (V):
R R (V) HO ( CHZCHO )m CH2CHOH
wherein m is an integer from 1 to 10 and R is hydrogen or a methyl or ethyl group. The reactions between molecules (a) and (b) and an alcohol are slower than the reactions between molecules (a) and (b) and an amine. A catalyst can be used and suitable catalysts include the tertiary amines and other catalysts mentioned above. It should be possible to encapsulate an alcohol by means of reactions between isocyanate moieties and anhydride moieties, glycidyl moieties or elecrophilic moieties bearing base-susceptible leaving and a diol. Reaction between anhydride moieties, for instance, and hydroxyl groups of the diol, in aqueous solution, should occur much more quickly than reaction between anhydride moieties and a hydroxyl group in organic solvent. This is particularly so if the aqueous solution contains a water-sol~Zble catalyst for the reaction, for instance a tertiary amine that reacts with the anhydride moiety to release an ionised moiety, which is drawn to the aqueous/organic interface.
The first liquid, that serves as the dispersed phase, is a liquid in which the first reactant can be dispersed or dissolved and in which any material to be encapsulated can be dispersed or dissolved. It should be immiscible, or at least only partially miscible, with the second liquid. While the limits on what is meant by "partially miscible" are not precise, in general a substance is considered to be water-immiscible if its solubility in water is less than about 0.5~
by weight. It is considered to be water-soluble if its solubility is greater than 98~, i.e., if 1 gram of the substance is put in 100 grams of water, 0.98 gram would dissolve. A substance whose solubility falls between these approximate limits is considered to be partially water-miscible. Desirably, the first liquid is a marginal solvent for the polymer reactant, and has a boiling point in the vicinity of 100°C. The properties of the first liquid, which will become encapsulated with the active material that is to be released, will affect the rate of release of that active material. Selection of a first liquid has to be made with these considerations in mind. Suitable candidates for use as the first liquid include alkylbenzenes such as toluene, xylene, ethers such as methyl tert.-butyl ether, ketones such as methylisobutylketone, esters such as ethyl acetate, propyl acetate, halogenated aliphatic hydrocarbons such as dichloromethane, and aliphatic nitriles such as butyronitrile.
Mixtures of solvents can be used. There can also be used co-solvents to change the properties of solvents or solvent mixtures. As co-solvents there are mentioned aliphatic liquids such as kerosene and also cyclic hydrocarbons such as cyclohexane. For instance, styrene-malefic anhydride copolymer containing 14% malefic anhydride is soluble in all of these solvents, whereas copolymer containing 50~ malefic anhydride is soluble only in ethylacetate, dichloromethane and butyronitrile.
The second liquid that forms the continuous phase is preferably water or an aqueous solution with water as the major component, or another polar solvent.
Surfactants and emulsifiers can be used to assist in dispersion of the first liquid, i.e. the oil phase, in the second liquid. Mention is made of poly(vinylalcohol), polyvinylpyrrolidones and nonylphenyl-oligo-ethylene glycol, available under the trademark IGEPAL. These are of formula:
HO(C H2C H20) n CgH19 where n has an average value from about 9 to about 13.
IGEPAL 630, indicating a molecular weight of about 630, is mentioned. IGEPAL 630 is preferred to poly(vinylalcohol) as it results in smaller microcapsules. Other suitable surfactants and emulsifiers include polyethyleneglycol alkyl ethers, for example C18H35 (OCH2CH2) nOH, where n has an approximate value of about 20, available under the trade-mark BRIJ 98.
Ionic surfactants can be used. Sodium dodecyl sulphate (SDS) is mentioned as an example of an anionic surfactant.
The first liquid can be dispersed in the second liquid by dropping the first liquid into a stirred bath of the second liquid. The first liquid then forms droplets throughout the continuous phase of the second liquid. The second reactant may be present in the second liquid before the first liquid is added. In an alternative embodiment, the second reactant is not present in the second liquid when the first liquid has been dispersed, but is added subsequently. In any event, the first and second reactants meet and react at the interface between the continuous and dispersed phases, that is, the surface of the droplets, and react to form the membrane.
The membrane-forming reaction can be carried out at a temperature above 0°C, at room temperature or at elevated temperature. If elevated temperature is used, the optimum temperature will depend on the boiling point of each of the solvents that make up the dispersed and continuous phases and that of the material to be encapsulated. No advantage is seen in using a temperature greater than about 70°C.
The concentration of each reactant in the liquid will affect the properties of the product. At low concentrations, the formed membranes will be thinner than at higher concentrations. It is preferred that the concentration of the moieties (a) plus (b) is not less than about 2%, and good results have been achieved with concentrations of 5-6%. If the concentration of moieties (a) plus (b) in the first liquid is up to about 10% there will probably be formed discrete microcapsules. At yet higher concentrations, discrete microcapsules are not formed but rather matrix particles in which the first liquid is entrapped. If the concentration is greater than about 15%, there will probably be formed a matrix.
It is a matter of routine experimentation not involving exercise of any inventive faculty to determine at which concentrations a particular system yields microcapsules and at which concentrations it yields a matrix. The malefic anhydride content of an SMA copolymer will affect the nature of the matrix. With SMA50 the membrane formed will tend to be more hydrophilic and the matrix may be a hydrogel. With a copolymer of lower malefic anhydride content, say SMA14, the membrane formed is amphiphilic rather than hydrophilic.
When microcapsules are formed from a first liquid having a density less than that of water, they float on top of the liquid present. They can be shipped in this form, or scooped off. When particles of a hydrogel matrix are formed, the liquid can be decanted from the porous solid matrix particles.
As examples of materials to be encapsulated, particular mention is made of insect pheromones. In the notation used below to describe the structure of the pheromones, the type (E or Z) and position of the double bond or bonds are given first, the number of carbon atoms in the chain is given next and the nature of the end group is given last. To illustrate, the pheromone Z-10 C19 aldehyde has the structure;
HOC-C~H 0 CH3(CH2)i \(CH2)8CH
Pheromones may in fact be mixtures of compounds with one component of the mixture predominating, or at least being a significant component. Mentioned as examples of significant or predominant components of insect pheromones, with the target species in brackets, are the following: E/Z-11 C14 aldehyde (Eastern Spruce Budworm), Z-10 C19 aldehyde (Yellow Headed Spruce Sawfly), Z-11 C14 acetate (Oblique Banded Leafroller), Z-8 C12 acetate (Oriental Fruit moth) and E,E-8,10 C12 alcohol (Codling moth).
An example of a ketone that is a pheromone is E or Z
7-tetradecen-2-one, which is effective with the oriental beetle. An ether that is not a pheromone but is of value is 4-allylanisole, which can be used to render pine trees unattractive to the Southern pine beetle.
In one preferred embodiment, the product of the microencapsulation process is a plurality of microcapsules having a size in the range of from about 1 to about 5000 ~,un, preferably 20 Eun to 2000 Eun. Particularly preferred microcapsules have sizes in the range from about 10 ~,un to about 60 Etm, more preferably about 20 to about 30 Vim, and an encapsulated pheromone contained within the membrane. The microcapsules can be used in suspension in water to give a suspension suitable for aerial spraying. The suspension may contain a suspending agent, for instance a gum suspending agent such as guar gum, rhamsan gum or xanthan gum.
Incorporation of a light stabilizer, if needed to protect encapsulated material, is within the scope of the invention. Suitable light stabilizers include the tertiary phenylene diamine compounds disclosed in Canadian Patent No.
1,179,682, the disclosure of which is incorporated by reference. The light stabilizer can be incorporated by dissolving it, with the pheromone, in the oil phase.
Antioxidants and UV absorbers can also be incorporated. Many hindered phenols are known for this purpose. Mention is made of antioxidants available from Ciba-Geigy under the trade-marks Irganox 1010 and 1076. As UV absorbers there are mentioned Tinuvin 292, 400, 123 and 323 available from Ciba-Geigy.
To assist in determining the distribution of sprayed microcapsules it is possible to include a coloured dye or pigment in the microcapsules. The dye should be oil-soluble and can be incorporated, with the pheromone, in the oil phase.
It will be used only in a small amount and will not significantly affect the membrane-forming reaction.
Alternatively, or additionally, an oil-soluble or oil-dispersible dye can be included in the aqueous suspension of microcapsules, where it is absorbed by the microcapsule shell.
Suitable oil-soluble or oil-dispersible dyes can be obtained from DayGlo Color Corporation, Cleveland, Ohio, and include Blaze Orange, Saturn Yellow, Aurora Pink, and the like.
Although the invention has been described largely with reference to encapsulation of pheromones, other molecules that are active in nature can be encapsulated in a similar manner. As examples there are mentioned linalool, terpineol, fenchone, and keto-decenoic acids and hydroxy-decenoic acids, which encourage activity of worker bees. Encapsulated 4-allylanisole can be used to make pine trees unattractive to the Southern pine beetle. Encapsulated 7,8-epoxy-2-methyloctadecane can be used to combat the nun moth or the gypsy moth. Natural flavours and fragrances can be encapsulated. All these applications, and microcapsules containing these materials, are within the scope of the present invention.
Other compounds of interest for encapsulation include mercaptans. Some animals mark territory by means of urine, to discourage other animals from entering that territory.
Examples of such animals include preying animals such as wolves, lions, dogs, etc. Ingredients in the urine of such animals include mercaptans. By dispersing microcapsules containing the appropriate mercaptans it is possible to define a territory and discourage particular animals from entering that territory. For example, the urine of a wolf includes a mercaptan, and distribution of microcapsules from which this mercaptan is gradually released to define a territory will discourage deer from entering that territory. Other materials that can be encapsulated and used to discourage approach of animals include essences of garlic, putrescent eggs and capsaicin.
Other compounds that can be included in the microcapsules of the invention include perfumes, pharmaceuticals, fragrances, flavouring agents and the like.
It is also possible to encapsulate materials for uses other than in nature. Mention is made of dyes, inks, adhesives and reactive materials that must be contained until they are to be used, for instance, by controlled release from a microcapsule or by rupture of a microcapsule.
Other materials that can be encapsulated are mentioned in PCT international application WO 98/45036 mentioned above, the disclosure of which is incorporated herein by reference.
The invention is further illustrated with reference to the accompanying drawings and the following non-limiting examples.
In some of the examples, dodecyl acetate was used as the material to be encapsulated and released. Dodecyl acetate is itself a component of the pheromone of many species, including the pod borer. Its properties also make it valuable as a mimic for other pheromones that contain ester moieties and are free of other active groups such as hydroxyl and aldehyde groups.
Figure 1 shows schematically an apparatus used in the examples;
Figures 2A, 2B, 2C 2D and 2E are optical photomicrographs of capsules produced by Example 1;
Figure 3 is an optical photomicrograph of microcapsules produced by Example 2;
Figure 4 is an optical photomicrograph of microcapsules produced by Example 3;
Figure 5 is a graphical illustration of release data of microcapsules produced by Examples lA and 1C.
Figure 6 is a graphical illustration of release data of microcapsules produced by Examples 1C and 2.
Example 1 The following experiments illustrate formation of microcapsules using a mixture of isocyanate and styrene-malefic anhydride copolymer as one of a pair of complementary reactants and tetraethylene pentamine as the other of the pair of reactants, using the apparatus shown schematically in Figure 1.
In each experiment the same aqueous phase and the same procedure were used. The copolymer was a styrene-malefic anhydride copolymer of 14~ malefic anhydride content, molecular weight 224,000, obtained from Aldrich. Distilled water containing 1.3s Igepal 630(30 ml) was stirred for 1-2 minutes and the first liquid, i.e., the oil phase was added.
Thereafter, 10 ml of dissolved water in which 2g of TEPA was distilled were added over 2-3 minutes. The procedure was carried out at room temperature.
As oil phase there were used 15 ml of an 11:4 mixture of p-xylene:dodecylacetate in which the following were dissolved:
(A) lg isocyanate (Mondur MRS), no SMA
(comparative);
(B) lg Mondur MRS plus 0.25g SMA14;
(C) lg Mondur MRS plus 0.5g SMA14~
(D) lg Mondur MRS plus lg SMA14; and (E) lg SMA14, no isocyanate (comparative).
Optical photomicrographs of the formed microcapsules and shown in Figures 2A, B, C, D and E.
Example 2 The procedure of the previous example was repeated with a mixture lg Mondur MRS and 0.5g SMA14 (224,000 mol. wt.), except that the reaction was carried out not at room temperature but at 70°C. The microcapsules formed are shown in Figure 3.
Example 3 The procedure of example 1 was repeated with a mixture of lg Mondur MRS and lg SMA14, except that as oil phase there was used l5 ml of an 11:4 mixture of ethyl acetate and dodecyl acetate. The microcapsules formed are shown in Figure 4.
Example 4 Release measurements were made on microcapsules prepared according to Examples lA, 1C and 2. An initial amount of 0.5 g was originally taken from each set of microcapsules.
The weight of each set of microcapsules was measured daily.
The weight of each set of microcapsules was expressed graphically as a percentage of the weight of the microcapsules on day one as a function of time in days. It can be seen from Figure 5 that the initial rate of release for polyurea-SMA14 microcapsules, prepared according to Example 1C, is approximately ten times greater than the rate of release from the polyurea capsules prepared according to Example lA. It can be seen from Figure 6 that the rate of release from capsules prepared according to Example 1C is approximately one order of magnitude greater than the rate of release from capsules prepared according to Example 2, that is, with the same formulation, but carried out at a temperature of 70°C. This release profile is suitable for pheromone-based insect mating control.
Claims (32)
1. A method of forming microcapsules or particles of a matrix which comprises dispersing a first liquid in a second, immiscible or partially miscible liquid that forms a continuous phase, one liquid containing reactants bearing (a) isocyanate moieties and (b) anhydride moieties, glycidyl moieties or electrophilic moieties bearing base-susceptible leaving groups, and the other liquid containing a reactant that bears reactive groups that will react with the reactants in the said one liquid to form a membrane.
2. A method according to claim 1, wherein the reactant bearing isocyanate moieties is a polymethylene polyphenylisocyanate of formula:
where n is 2 to 4.
where n is 2 to 4.
3. A method according to claim 1 or 2, wherein the reactant that will react with the reactants in the said one liquid is a polyamine.
4. A method according to claim 1 or 2, wherein the reactant that will react with the reactants in the said one liquid is a polyol.
5. A method according to claim 1 or 2, wherein the reactant that will react with the reactants in the said one liquid is a compound that contains amino groups and hydroxy groups.
6. A method according to any one of claims 1 to 5, wherein the reactants in the said one liquid bear isocyanate moieties and anhydride moieties.
7. A method according to claim 6, wherein the anhydride moieties are present in a copolymer of an unsaturated polymerisable anhydride and an unsaturated copolymerisable monomer.
8. A method according to claim 7, wherein the unsaturated polymerisable anhydride is maleic anhydride.
9. A method according to claim 7 or 8, wherein the unsaturated copolymerisable monomer is styrene.
10. A method according to any one of claims 1 to 9, wherein the molar ratio of isocyanate moieties, anhydride moieties, glycidyl moieties or electrophilic moieties bearing base-susceptible leaving groups is in the range from 1:99 to 99:1.
11. A method according to claim 10, wherein the molar ratio is 1:95 to 95:1.
12. A method according to claim 3, wherein the polyamine is a compound of formula (I) H2N (CH2)n NH2 (I) wherein n is an integer from 2 to 10, or a compound of formula (II) wherein m is an integer from 1 to 1000 and R is hydrogen or a methyl or ethyl group, a primary/secondary/tertiary amine in which a hydrogen atom attached to one or more internal nitrogen atoms of a compound of formula (II) is replaced by a lower aminoalkyl group, or a polyetheramine of general formula (III) :
wherein r is an integer from 1 to 20.
wherein r is an integer from 1 to 20.
13. A method according to claim 12, wherein the polyamine is a compound of Formula (I) in which n is an integer from 2 to 6.
14. A method according to claim 12, wherein the polyamine is a compound of formula (II) in which m is an integer from 1 to 10.
15. A method according to claim 3, wherein the polyamine is tetraethylenepentamine.
16. A method according to claim 4, wherein the polyol is a compound of formula (IV) HO (CH2)n OH (IV) where n is an integer from 2 to 10, or a compound of formula V
wherein m is an integer from 1 to 10 and R is hydrogen or a methyl or ethyl group.
wherein m is an integer from 1 to 10 and R is hydrogen or a methyl or ethyl group.
17. A method according to claim 16, wherein the polyol is a compound of Formula (IV) in which n is an integer of 2 to 4.
18. A method according to any one of claims 1 to 17, wherein the first liquid is a water-immiscible or partially water-immiscible liquid and the second liquid is an aqueous liquid.
19. A method according to claim 18, wherein the second liquid contains an emulsifier or surfactant.
20. A method according to any one of claims 1 to 19, wherein there is present in the second liquid a tertiary amine as catalyst.
21. A method according to any one of claims 1 to 20, wherein there is present in the first liquid a material to be encapsulated.
22. A method according to claim 21, wherein the material to be encapsulated is an alcohol.
23. A method according to claim 22, wherein the alcohol is a C14 or a C16 alcohol.
24. A method according to claim 21, 22 or 23, wherein the material to be encapsulated is a semiochemical.
25. A method according to claim 21, 22 or 23, wherein the material to be encapsulated is a pheromone.
26. A method according to claim 22, wherein the alcohol is codling moth pheromone.
27. Microcapsules or particles of a matrix formed by reaction, at an interface, between reactants bearing (a) isocyanate moieties and (b) anhydride moieties, glycidyl moieties or electrophilic moieties bearing base-susceptible leaving groups, and a reactant that bears reactive groups that will react with the reactants bearing (a) and (b) to form a membrane.
28. Microcapsules or particles of a matrix according to claim 27, which are formed by reaction between isocyanate moieties present in a polymethylene polyphenylisocyanate, anhydride moieties present in a styrene-anhydride copolymer, and a polyamine.
29. Microcapsules or particles according to claim 27 or 28 containing a material that undergoes controlled-release from the capsule.
30. Microcapsules or particles according to claim 29, wherein the material that undergoes controlled release is a semiochemical.
31. Microcapsules or particles according to claim 30, wherein the semiochemical is a pheromone.
32. A method of controlling insect populaton or behaviour which comprises applying to the habitat of the insects microcapsules or particles of a matrix, defined according to any one of claims 28 to 30.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2311192 CA2311192A1 (en) | 2000-06-12 | 2000-06-12 | Encapsulation process using isocyanate moieties |
| PCT/CA2001/000846 WO2001096011A1 (en) | 2000-06-12 | 2001-06-11 | Encapsulation process using isocyanate moieties |
| AU2001267202A AU2001267202A1 (en) | 2000-06-12 | 2001-06-11 | Encapsulation process using isocyanate moieties |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA 2311192 CA2311192A1 (en) | 2000-06-12 | 2000-06-12 | Encapsulation process using isocyanate moieties |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2311192A1 true CA2311192A1 (en) | 2001-12-12 |
Family
ID=4166448
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2311192 Abandoned CA2311192A1 (en) | 2000-06-12 | 2000-06-12 | Encapsulation process using isocyanate moieties |
Country Status (3)
| Country | Link |
|---|---|
| AU (1) | AU2001267202A1 (en) |
| CA (1) | CA2311192A1 (en) |
| WO (1) | WO2001096011A1 (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005528200A (en) * | 2002-05-31 | 2005-09-22 | マクマスター・ユニバーシテイ | Method for encapsulating hydrophobic organic molecules in polyurea capsules |
| MX2007001369A (en) | 2004-08-04 | 2007-04-10 | Ciba Sc Holding Ag | Functionalized particles. |
| GB0802489D0 (en) | 2008-02-11 | 2008-03-19 | Givaudan Sa | Product |
| EP2399667B1 (en) * | 2010-06-25 | 2017-03-08 | Cognis IP Management GmbH | Process for producing microcapsules |
| US8653190B2 (en) | 2011-08-08 | 2014-02-18 | 3M Innovative Properties Company | Curable cyclic anhydride copolymer/silicone composition |
| GB2496330B (en) | 2013-01-21 | 2016-06-29 | Rotam Agrochem Int Co Ltd | Preparation of an agrochemical active composition encapsulated in cross linked polyurea |
| CN114515554A (en) * | 2022-01-18 | 2022-05-20 | 国家石油天然气管网集团有限公司 | Preparation method of poly alpha-olefin drag-reducing high-molecular polymer microcapsule |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA811414B (en) * | 1980-03-05 | 1982-03-31 | Nat Res Dev | Stabilised compositions containing behaviour modifying compounds |
| JPS56144739A (en) * | 1980-04-10 | 1981-11-11 | Mitsubishi Paper Mills Ltd | Preparation of microcapsule |
| FR2610537A1 (en) * | 1987-02-11 | 1988-08-12 | Rhone Poulenc Chimie | IMPROVED MICROENCAPSULATION METHOD BY INTERFACIAL POLYADDITION |
| EP0551796B1 (en) * | 1992-01-03 | 1997-08-13 | Novartis AG | Microcapsule suspension and a process for its preparation |
-
2000
- 2000-06-12 CA CA 2311192 patent/CA2311192A1/en not_active Abandoned
-
2001
- 2001-06-11 AU AU2001267202A patent/AU2001267202A1/en not_active Abandoned
- 2001-06-11 WO PCT/CA2001/000846 patent/WO2001096011A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001096011A1 (en) | 2001-12-20 |
| AU2001267202A1 (en) | 2001-12-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0973606B1 (en) | Encapsulation process and encapsulated products | |
| CA2487352C (en) | Method of encapsulating hydrophobic organic molecules in polyurea capsules | |
| Scher et al. | Microencapsulation of pesticides by interfacial polymerization utilizing isocyanate or aminoplast chemistry | |
| AU776909B2 (en) | Hydrogel microbeads having a secondary layer | |
| US4497793A (en) | Microencapsulated naturally occuring pyrethrins | |
| AU775877B2 (en) | Active material within hydrogel microbeads | |
| JPH0568300B2 (en) | ||
| PL196973B1 (en) | Acid-triggered release microcapsules | |
| WO2001094002A2 (en) | Novel emulsions | |
| GB1558460A (en) | Encapsulation process | |
| ZA200509093B (en) | Encapsulated essential oils | |
| EP1292387B1 (en) | Encapsulation process using anhydride moieties | |
| CA2311192A1 (en) | Encapsulation process using isocyanate moieties | |
| AU660779B2 (en) | Process for formaldehyde content reduction in microcapsule formulations | |
| CA2311195A1 (en) | Photostimulated phase separation encapsulation | |
| CA2411931A1 (en) | Encapsulation process using anhydride moieties | |
| AU764309B2 (en) | Encapsulation process and encapsulated products | |
| CA1118222A (en) | Microencapsulated trifluoralin | |
| Chamberlain et al. | Polymeric formulations of pest control agents | |
| Stem et al. | Microencapsulation Technology | |
| MXPA99008946A (en) | Encapsulation process and encapsulated products | |
| PT79155B (en) | Microencapsulated naturally occuring pyrethrins |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |