U.S. patent application number 12/158797 was filed with the patent office on 2009-10-29 for formulation.
This patent application is currently assigned to SYNGENTA CROP PROTECTION, INC.. Invention is credited to Michael Chavant, Patric Joseph Mulqueen, Ian Malcolm Shirley, Anne Waller.
Application Number | 20090269382 12/158797 |
Document ID | / |
Family ID | 35841212 |
Filed Date | 2009-10-29 |
United States Patent
Application |
20090269382 |
Kind Code |
A1 |
Mulqueen; Patric Joseph ; et
al. |
October 29, 2009 |
FORMULATION
Abstract
A product comprising microcapsules which themselves comprise (a)
a polymeric shell; and (b) a core comprising an agrochemical which
has a melting point greater than or equal to 25.degree. C.
characterised in that the agrochemical is dispersed as a solid in a
hydrophobic material which has a melting point greater than or
equal to 25.degree. C. but which does not exhibit a glass
transition temperature.
Inventors: |
Mulqueen; Patric Joseph;
(Bracknell, GB) ; Waller; Anne; (Bracknell,
GB) ; Shirley; Ian Malcolm; (Bracknell, GB) ;
Chavant; Michael; (Bracknell, GB) |
Correspondence
Address: |
SYNGENTA CROP PROTECTION , INC.;PATENT AND TRADEMARK DEPARTMENT
410 SWING ROAD
GREENSBORO
NC
27409
US
|
Assignee: |
SYNGENTA CROP PROTECTION,
INC.
Greensboro
NC
|
Family ID: |
35841212 |
Appl. No.: |
12/158797 |
Filed: |
December 22, 2006 |
PCT Filed: |
December 22, 2006 |
PCT NO: |
PCT/GB06/04902 |
371 Date: |
November 21, 2008 |
Current U.S.
Class: |
424/408 ;
514/229.2; 514/341; 514/342; 514/357; 514/365 |
Current CPC
Class: |
A01N 25/006 20130101;
A01N 43/50 20130101; A01N 25/32 20130101; A01N 25/28 20130101; A01N
43/40 20130101; A01N 43/88 20130101; A01N 43/78 20130101; A01N
25/28 20130101; A01N 25/02 20130101; A01N 25/04 20130101; A01N
25/10 20130101; A01N 47/40 20130101; A01N 47/40 20130101; A01N
51/00 20130101 |
Class at
Publication: |
424/408 ;
514/357; 514/365; 514/341; 514/342; 514/229.2 |
International
Class: |
A01N 25/28 20060101
A01N025/28; A01N 47/40 20060101 A01N047/40; A01N 51/00 20060101
A01N051/00; A01P 7/04 20060101 A01P007/04 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 23, 2005 |
GB |
0526416.3 |
Claims
1. A product comprising microcapsules which themselves comprise (a)
a polymeric shell; and (b) a core comprising an agrochemical which
has a melting point greater than or equal to 25.degree. C.
characterised in that the agrochemical is dispersed as a solid in a
hydrophobic material which has a melting point greater than or
equal to 25.degree. C. but which does not exhibit a glass
transition temperature.
2. A product as claimed in claim 1 where the agrochemical has a
water-solubility in the range of 0.1 to 100 g/l at 20.degree.
C.
3. A product as claimed in claim 2 where the agrochemical is a
neonictinoid insecticide.
4. A product as claimed in claim 3 where the agrochemical is
acetamiprid, clothianidin, imidacloprid, thiacloprid or
thiamethoxam.
5. A product as claimed in claim 4 where the agrochemical is
thiamethoxam.
6. A product as claimed in claim 1 to where the microcapsules are
dispersed in an aqueous phase.
7. A product as claimed in claim 1 to where the product is a dry
product.
8. A product as claimed in claim 7 where the dry product is
granular.
9. A product as claimed in claim 7 where the dry product is
water-dispersible.
10. A product as claimed in claim 6 where the aqueous phase
comprises an agrochemical.
11. A product as claimed in claim 10 where the agrochemical in the
aqueous phase has a water-solubility in the range of 0.1 to 100 g/l
at 20.degree. C.
12. A product as claimed in claim 11 where the agrochemical in the
aqueous phase is a neonictinoid insecticide.
13. A product as claimed in claim 12 where the agrochemical in the
aqueous phase is acetamiprid, clothianidin, imidacloprid,
thiacloprid or thiamethoxam.
14. A product as claimed in claim 13 where the agrochemical in the
aqueous phase is thiamethoxam.
15. A product as claimed in claim 1 where the core also comprises a
water-immiscible liquid.
16. A product as claimed in claim 1 where the hydrophobic material
is a wax.
17. A product as claimed in claim 1 where the core is fully or
partially solid.
18. A product as claimed in claim 1 where the core is partially
solid.
19. A product as claimed in claim 1 where the polymeric shell is a
polymer which is a polyurea, a polyamide or a polyurethane or is a
mixture of two or more of these polymers.
20. A product as claimed in claim 19 where the polymeric shell is a
polyurea.
21. A process for preparing a product as claimed in claim 1
comprising the steps (i) melting the hydrophobic material to form a
hydrophobic liquid; (ii) dispersing the agrochemical in the
hydrophobic liquid; (iii) emulsifying the hydrophobic liquid into
an aqueous phase; (iv) optionally cooling the resultant emulsion;
(v) causing an interfacial polymerisation reaction to occur at the
interface between the hydrophobic liquid and the aqueous phase to
produce a capsule suspension; and (vi) optionally allowing or
causing the capsule suspension to cool.
22. A process as claimed in claim 21 which comprises the step of
rapidly cooling an emulsion to below the melting point of the
hydrophobic material.
23. A process as claimed in claim 21 where an isocyanate is
introduced through the aqueous phase.
24. (canceled)
25. (canceled)
26. (canceled)
27. (canceled)
28. (canceled)
29. (canceled)
Description
[0001] This invention relates to novel microcapsules which comprise
a biologically active compound and processes for the preparation
and for the use of such microcapsules. In particular it relates to
a product comprising microcapsules which themselves comprise
(a) a polymeric shell; and (b) a core which comprises an
agrochemical which has a melting point above 25.degree. C.
characterised in that the agrochemical is dispersed as a solid in a
hydrophobic material which has a melting point greater than or
equal to 25.degree. C. but which does not exhibit a glass
transition temperature.
[0002] Microcapsule technology has been in existence for a number
of years. Microcapsules have a variety of uses, especially for
containing dyes, inks, chemical reagents, pharmaceuticals,
flavouring materials, and more especially agrochemicals, that is
fungicides, bactericides, insecticides, herbicides and the
like.
[0003] Microencapsulated formulations of agrochemicals may be
exploited in a wide range of applications both in crop protection
and professional products outlets, and may be applied via a variety
of methods such as foliar sprays, soil application and as seed
treatments. Such formulations allow the release rate of the
agrochemical to be controlled over a desired period of time and
find applications for weed, fungal or insect control, as
termiticides, residual sprays, turf treatments and as seed
treatments (amongst others).
[0004] In commercial use, agrochemical products are subject to a
range of environmental factors which result in a reduction in
efficacy of the formulation, including run-off and leaching from
soil (which may lead to groundwater contamination), rainfastness
and wash-off from seeds; water-soluble active compounds are
particularly susceptible to such losses.
[0005] The microcapsules of this invention are useful for
controlling the release rate of the solid water-soluble
biologically active compound, where the biologically active
compound is a pesticide [agrochemical], and are particularly useful
for controlling the release into any medium where water is present,
eg. release of pesticidally active compounds into soil. The
microcapsules are even more particularly useful for controlling the
release of water-soluble pesticidally active compounds into soil
with a high moisture content as a result of heavy rainfall or
excessive irrigation. A further advantage is that such products can
also reduce the amount of water soluble product that is leached to
lower soil levels by heavy rainfall or irrigation.
[0006] Such uses may include application of these products in crop
protection for the use of insecticides in vegetable crops to extend
the performance of a product in soil; use of such a product to
provide long term release characteristics in specific market
sectors such as control of termites; use of such a product to
increase the period of performance on turf, when formulated
together with fertilisers as a granule, or applied directly to turf
by an appropriate application method and which is then subjected to
high levels of irrigation (as commonly employed on golf-courses);
use of such products for the protection of seeds where applied
prior to sowing and combined with appropriate inerts to provide
efficient coating of the seeds; and use of such a product to
provide a longer lasting residual deposit where a long lasting
deposit may be required.
[0007] Several technologies are commonly known as being useful in
the production of microcapsules (for example as described in
chapter 4 of "Controlled Delivery of Crop Protection Agents", pub.
Taylor and Francis, London 1990). One such technology of particular
utility for the encapsulation of agrochemicals is interfacial
polymerisation in which the walls of the microcapsules are
generally formed of polymeric material produced by a polymerisation
reaction which preferably takes place at the interface between two
phases, usually an aqueous phase and a water-immiscible organic
phase. Thus, they may be produced from a water-in-oil emulsion or
more usually an oil-in-water emulsion.
[0008] Microcapsules which comprise, in the organic phase,
suspensions of solid biologically active compounds in organic
solvents or liquid biologically active compounds are known (e.g. as
described in patent documents WO 95/13698, EP 0730406, U.S. Pat.
No. 5,993,842 and U.S. Pat. No. 6,015,571, the contents of which
are fully incorporated herein by reference).
[0009] Processes for the microencapsulation of water-soluble
biologically active compounds are also known, but in these the
biologically active compound is generally dissolved in water or a
water-miscible solvent prior to encapsulation.
[0010] It has now been found that it is possible to encapsulate
solid agrochemical compounds which are dispersed in a substantially
water-immiscible phase, in which the agrochemical is dispersed in a
hydrophobic material which ha a melting point greater than or equal
to 25.degree. C. but which does not exhibit a glass transition
temperature.
[0011] In our co-pending application (which claims priority from
the same patent application as this application) one particular
method of producing a similar effect of having an agrochemical
dispersed in a diffusion limiting structure is to produce an at
least partially solid matrix in which the agrochemical is retained
more effectively. In that particular case, the (non-continuous)
matrix is formed via an interfacial polymerisation of an
oil-in-water emulsion, in which the solid water-soluble
biologically active material is dispersed within the oil.
Surprisingly, in that invention carrying out said interfacial
polymerisation results in the formation of a polymer
(non-continuous) matrix which is distributed throughout the
microcapsules, rather than being restricted to the interface, as is
commonly taught in the prior art.
[0012] There are several problems which must be overcome for the
successful encapsulation of a suspension of solid particles within
a microcapsule formed by interfacial polymerisation of an
oil-in-water emulsion.
[0013] Firstly, a stable suspension of the solid in a substantially
water-immiscible liquid must be produced. If dispersants or
surfactants are used, they must not interfere with any further
processes of dispersion used in making microcapsules.
[0014] Secondly, the suspension must be dispersed in water to
produce stable, well dispersed droplets. For biologically active
substances, it is preferable to have very small droplets of liquid
dispersed in water so as to present a high surface area of the
resulting microcapsules. To produce very small droplets requires
high shear forces which would tend to break down the droplets
and/or release the solid from suspension. Surfactants are usually
required to achieve good dispersion and stable droplets.
[0015] Thirdly, the presence of one or more surfactants may make
the dispersed droplet system unstable and the phenomenon of phase
inversion may occur, i.e. water forms small droplets within the
liquid; a water-in-oil emulsion.
[0016] Fourthly, the solid suspended in the water-inuniscible
liquid is liable to migrate to the aqueous phase, particularly when
emulsifying surfactants are used.
[0017] The last three of these problems is even more challenging to
overcome for the encapsulation of water-soluble biologically active
compounds, and it has been found that modifications are required to
the procedures described in patent documents WO 95/13698, EP
0730406, U.S. Pat. No. 5,993,842, U.S. Pat. No. 6,015,571, US
2003/0119675 and JP 2000247821 for the encapsulation of suspensions
of water-insoluble compounds.
[0018] It has now been found that it is possible to produce
microcapsules which comprise a solid water-soluble, biologically
active compound dispersed in a (non-continuous) matrix which is at
least partially solid and which is distributed throughout the
microcapsules. Moreover it has been found that the release rate of
the biologically active compound can be varied over an extremely
wide range; surprisingly very slow release rates into aqueous media
are possible despite the water-solubility of the compound. This
confers useful benefits to products utilising such technology.
[0019] One very suitable technique for the formation of said
microcapsules is interfacial polymerisation via an oil-in-water
emulsion; surprisingly, this results in the formation of a polymer
(non-continuous) matrix which is distributed throughout the
microcapsules, rather than being restricted to the interface, as is
commonly taught in the prior art.
[0020] The microcapsules may be produced using the following
methodology:
Step 1--producing the solid water-soluble, biologically active
compound with the required particle size, suitably by a milling
process. A suitable Volume Median Diameter [VMD] particle size of
the solid is 0.01-50 .mu.m; more suitably the lower limit is 0.5
.mu.m and even more suitably the lower limit is 1.0 .mu.m; more
suitably the upper limit is 10 .mu.m and even more suitably the
upper limit is 5 .mu.m. Step 2--suspending the solid water-soluble,
biologically active compound in a substantially water-immiscible
liquid. The liquid is preferably a poor solvent for the solid, i.e.
it will not dissolve significant quantities of the solid.
[0021] The liquid preferably contains a dispersant capable of
keeping the solid in the liquid but which does not allow the solid
to be extracted into the water when the suspension is dispersed
into water. In addition, when the suspension is added to water, the
dispersant must not allow phase inversion to occur.
[0022] Alternatively, the procedures of steps 1 and 2 may be varied
by performing a milling process to reduce the particle size of the
solid water-soluble, biologically active compound, after the
compound has been suspended in the substantially water-immiscible
liquid (media milling).
Step 3--a physical dispersion of the organic phase in an aqueous
phase is prepared. To obtain the appropriate dispersion, the
organic phase is added to the aqueous phase, with stirring. A
suitable dispersing means is employed to disperse the organic phase
in the aqueous phase. Selection of dispersion process and apparatus
will depend upon the desired particle size of the emulsion (and
ultimate product) to be produced. One suitable means of dispersion
is typically a high shear rotor/stator device (such as a laboratory
Silverson.TM. machine) for small (<10 micron VMD products) but
other means can be employed such as Cowles.TM. dissolvers, simple
mixing devices for larger particle sizes and even high pressure
homogenisation equipment. Choice of such equipment is within the
scope of one skill in the art. A suitable means may be any high
shear device so as to obtain a desired droplet (and corresponding
microcapsule particle) size within the range from about 1 to about
200 .mu.m; suitably from about 1 to 150 .mu.m; more suitably from
about 1 to about 50 .mu.m; and most suitably from about 3 to about
50 .mu.m, VMD. Once the desired droplet size is obtained, the
dispersion means is discontinued. Only mild agitation is required
for the remainder of the process. The organic phase comprises the
solid water-soluble, biologically active compound suspended in the
substantially water-immiscible liquid to be encapsulated prepared
as described above in steps 1 and 2. The aqueous phase comprises
water and at least one emulsifier and/or protective colloid.
[0023] Clearly there is a relationship between the particle size of
the solid water-soluble, biologically active compound and the
particle size of the microcapsules; in order to obtain control over
the release rate of the biologically active compound, the VMD ratio
of the particle size of this compound to that of the microcapsules
will be typically of the value 1:5; suitably in the range 1:3 to
1:100; more suitably 1:5 to 1:20.
[0024] In order to obtain the microcapsules, the organic phase
and/or the aqueous phase must contain one or more materials which
can react to form a polymer. In one preferred embodiment, the
organic phase contains at least one diisocyanate and/or
polyisocyanate, whilst the aqueous phase contains at least one
diamine and/or polyamine. In the situation where at least one
diamine and/or polyamine is included in the aqueous phase, this
component is added to the aqueous phase after the formation of the
oil-in-water emulsion as described above in step 3.
Step 4--at least one diamine and/or polyamine is added to the
oil-in-water emulsion through the aqueous phase, maintaining mild
agitation throughout. Stirring is continued typically for 30
minutes to 3 hours until the formation of the (non-continuous)
matrix is complete. The reaction temperature is generally in the
range from about 20.degree. C. to about 60.degree. C. In the
situation where approximately equimolar amounts of isocyanate and
amino groups are present, the reaction temperature is preferably
from about 20.degree. C. to about 40.degree. C., and even more
preferably from about 20.degree. C. to about 30.degree. C. In the
situation where an excess of isocyanate groups are present, the
reaction temperature is preferably from about 30.degree. C. to
about 60.degree. C., and even more preferably from about 40.degree.
C. to about 50.degree. C. Reaction times in excess of 3 hours
combined with temperatures of 60.degree. C. or above are not
recommended; such conditions have been utilised for the
encapsulation of suspensions of water-insoluble compounds (US
2003/0119675 and JP 2000247821) but it has been found that such
conditions are not suitable for the formation of the microcapsules
of this invention, as they result in poor encapsulation efficiency
(the water-solubility of the active compounds increases with
increasing temperature, resulting in excessive quantities of the
active compound transferring into the aqueous phase).
[0025] To form a (non-continuous) matrix, many other
microencapsulation techniques are possible, including:
(i) Preparation of a microcapsule in which a monomer is present in
the disperse phase and is caused to undergo polymerisation to form
the (non-continuous) matrix. Such monomers should be essentially
water immiscible and typically comprise a vinyl reactive monomer,
for example, C1-C16 alkyl esters of acrylic and methacrylic acid
such as ethyl hexyl acrylate and ethyl hexyl methacrylate.
Cross-linking may also be introduced by choice of an appropriate
acrylate or methacrylate monomer such as glycidyl methacrylate;
(ii) preparation of a microcapsule in which the solid
water-soluble, biologically active compound is dispersed within a
liquid in which a reagent is dissolved, and in which the liquid and
reagent are caused to react to form the (non-continuous) matrix.
Such effects may be achieved by two reactive species, as are
required to produce a polyurethane. These include organic liquid
soluble polyols to react with a suitable isocyanate. When the
isocyanate reactive species has sufficient functionality, the
polyol may contain just one polymerisable hydroxyl group. Many
chemistries qualify including alcohols and surfactant products
derived from alkoxylation processes (including ethylene oxide,
propylene oxide and butylene oxide or mixtures thereof. When the
isocyanate has less functionality or where high degrees of cross
linking are desired within the (non-continuous) matrix, the polyol
component may comprise more than one polymerisable OH (hydroxyl)
functional compounds, suitably comprising two or more hydroxyl
groups, per molecule on average. The polymerisable, hydroxyl
functional compounds may be aliphatic and/or aromatic. The
polymerizable, hydroxyl functional compounds may be straight,
cyclical, fused, and/or branched. Particular polymerizable hydroxyl
functional compounds include at least one diol, at least one triol,
and/or at least one tetrol. Any of these polyol compounds may be
monomeric, oligomeric, and/or polymeric as desired. If oligomeric
and/or polymeric, the polyol(s) may be selected from one or more
hydroxyl functional polyethers, polyesters, polyurethanes,
polyacrylics, epoxy resins, polyamides, polyamines, polyureas,
polysulfones, combinations of these, or the like. Polyether polyols
such as the polyalkylene ether and polyester polyols are also
suitable and these are commercially available at relatively low
cost and are hydrolytically stable.
[0026] Suitable polyalkylene ether polyols include poly(alkylene
oxide) polymers which are essentially water immiscible and organic
soluble, such as poly(ethylene oxide) and poly(propylene oxide)
polymers and copolymers with terminal hydroxyl groups derived from
polyhydric compounds, including diols and triols; for example,
ethylene glycol, propylene glycol, 1,3-butane diol, 1,4-butane
diol, 1,6-hexanediol, neopentyl glycol, diethylene glycol,
dipropylene glycol, pentaerythritol, glycerol, diglycerol,
trimethylol propane and similar low molecular weight polyols.
Suitable commercially available polyether polyols include those
sold under the trade name Voranolo.RTM. (The Dow Chemical
Company).
[0027] The polyester polyols which are suitable in accordance with
the invention include known polycondensates of organic dihydroxy
and optionally polyhydroxy (trihydroxy, tetrahydroxy) compounds and
dicarboxylic and also optionally polycarboxylic (tricarboxylic,
tetracarboxylic) acids or hydroxycarboxylic acids or lactones.
Instead of the free polycarboxylic acids it is also possible to use
the corresponding polycarboxylic anhydrides or corresponding
polycarboxylic esters of lower alcohols to prepare the polyesters
such as, for example, phthalic anhydride. Examples of suitable
diols are ethylene glycol, 1,2-butanediol, diethylene glycol,
triethylene glycol, polyalkylene glycols, such as polyethylene
glycol, and also 1,2- and 1,3-propanediol, 1,4-butanediol,
1,6-hexanediol, neopentyl glycol or neopentyl glycol
hydroxypivalate. Examples of polyols having 3 or more hydroxyl
groups in the molecule, which may be used additionally, if desired,
include trimethylolpropane, trimethylolethane, glycerol,
erytlritol, pentaerythritol, di-trimethylolpropane,
dipentaerythritol, trimethylol-benzene and trishydroxyethyl
isocyanurate.
[0028] A particularly suitable class of polyols useful in the
compositions, coatings and methods of the invention are the water
insoluble phthalic anhydride based polyester-ether polyols which
are described, for example, in U.S. Pat. No. 6,855,844 which is
incorporated by reference herein. Suitable commercially available
phthalic anhydride based polyester-ether polyols include the
"Stepanpols".RTM. (Stepan Company).
[0029] Other relatively simple feedstocks include natural products
that contain reactive hydroxyl groups such as castor oil These
systems require the addition of a suitable catalyst that may be
added as needed to any of the phases in the formulation. Suitable
catalysts are well known in the art but include organometal
catalysts such as dibutyl tin dilaurate and tertiary amines such as
triethylamine and triisopropanolamine; and
(iii) preparation of a microcapsule wherein a (non-continuous)
matrix-forming compound is caused to separate within the
microcapsule by removal of a volatile solvent for that compound.
This may be achieved by firstly preparing a dispersion of the solid
water-soluble biologically active compound in a solution of a water
insoluble (non-continuous) matrix forming polymer and a water
immiscible volatile solvent for that water insoluble
(non-continuous) matrix forming polymer, secondly forming an
emulsion of this water-immiscible mixture in water, stabilising
that emulsion by an appropriate technique and then removing the
volatile solvent by a suitable evaporation process, yielding a
dispersion in water of microcapsules containing the water-soluble
biologically active compound distributed throughout a
(non-continuous) matrix of the water insoluble polymer. The
stabilisation of the intermediate emulsion may be achieved by any
suitable microencapsulation process, such as an interfacial
polycondensation by the routes well known and outlined above but
also by such routes as identified in U.S. Pat. No. 5,460,817, where
the technology is identified as being useful for water insoluble
(and oil soluble) biologically active compounds such as
chlorpyrifos and trifluralin but does not refer to utility for
dispersions in an oil or polymer of a solid water-soluble
biologically active compound.
[0030] In this present invention, the matrix is provided by a
hydrophobic solid with a melting point greater than 25 C and which
does not exhibit a glass transition temperature. This involves the
preparation of a microcapsule in which the agrochemical is
dispersed within a hydrophobic solid which is held above its
melting point during processing, and is subsequently allowed to
solidify by cooling. Further embodiments are possible whereby the
hydrophobic solid is mixed with water immiscible organic liquids
such that the combination mixture still shows a melting point above
25 C. Such products encompass the use of waxes with a melting point
above ambient temperature (25.degree. C.) and include paraffin wax,
carnauba wax, beeswax, and other natural, synthetic or
semi-synthetic waxes. The encapsulation process may be carried out
in a dispersion in water of the molten material at a suitable
temperature during which a polymer shell is caused to separate at
the interface between the dispersed oil phase and water and where
the dispersion in water of the molten material itself contains the
dispersed solid water-soluble biologically active compound. This
dispersion of solid in a molten material can be prepared by typical
techniques of grinding technical biologically active compound in
the molten material or by dispersing previously ground dry
technical biologically active compound into molten material. Other
techniques for achieving this would be apparent to a skilled
person.
[0031] In the preparation of such microcapsules, it is naturally
assumed that any substantially water immiscible liquid (or
hydrophobic solid) used for the preparation of the dispersion of
the solid water-soluble biologically active compound will be
essentially retained within the microcapsule (unless removed
deliberately by evaporation as discussed above). Undesired loss of
solvent (or hydrophobic solid) may alter (or destabilise) the
capsule structure and release characteristics. One preferred
embodiment of the capsule is where the water-immiscible liquid
(and/or hydrophobic solid) does not migrate into the water phase
and, moreover, is involatile such that drying operations on the
aqueous compositions do not result in solvent loss and thus
alteration of the desired capsule composition.
[0032] The microcapsules of this invention may be produced using
the following methodology:
Step 1--producing the solid agrochemical with the required particle
size, suitably by a milling process. A suitable Volume Median
Diameter [VMD] particle size of the solid is 0.01-50 .mu.m; more
suitably the lower limit is 0.5 .mu.m and even more suitably the
lower limit is 1.0 .mu.m; more suitably the upper limit is 10 .mu.m
and even more suitably the upper limit is 5 .mu.m. Step
2--suspending the solid agrochemical in a substantially
water-immiscible liquid (or molten mixture with hydrophobic solid
or molten hydrophobic solid). The liquid (or molten mixture with
hydrophobic solid or molten hydrophobic solid) is preferably a poor
solvent for the solid, i.e. it will not dissolve significant
quantities of the solid.
[0033] The liquid preferably contains a dispersant capable of
keeping the solid in the liquid but which does not allow the solid
to be extracted into the water when the suspension is dispersed
into water. In addition, when the suspension is added to water, the
dispersant must not allow phase inversion to occur.
[0034] Alternatively, the procedures of steps 1 and 2 may be varied
by performing a milling process to reduce the particle size of the
solid agrochemical, after the compound has been suspended in the
substantially water-immiscible liquid (or molten mixture with
hydrophobic solid or molten hydrophobic solid) (media milling).
[0035] In this case, the hydrophobic meltable solid is held above
its melting point and the milling operation is carried out at such
an elevated temperature. Alternatively, the agrochemical may be
separately milled to the required size in a dry milling operation
and added to a molten hydrophobic solid, or it may be milled in a
water immiscible organic liquid and added to molten hydrophobic
solid. In exceptional circumstances, it is possible to mill in an
aqueous medium and with appropriate selection of surfactants,
disperse the aqueous mill base as a water-in-oil emulsion to the
molten hydrophobic solid.
Step 3--a physical dispersion of the organic phase in an aqueous
phase is prepared. To obtain the appropriate dispersion, the
organic phase is added to the aqueous phase, with stirring. Clearly
to achieve this part of the process, the temperature at which the
process is conducted is above the melting point of the hydrophobic
solid (or mixture of hydrophobic solid with suitable
water-immiscible liquid). A suitable dispersing means is employed
to disperse the organic phase in the aqueous phase. Selection of
dispersion process and apparatus will depend upon the desired
particle size of the emulsion (and ultimate product) to be
produced. One suitable means of dispersion is typically a high
shear rotor/stator device (such as a laboratory Silverson.TM.
machine) for small (<10 micron VMD products) but other means can
be employed such as Cowles.TM. dissolvers, simple mixing devices
for larger particle sizes and even high pressure homogenisation
equipment. Choice of such equipment is within the scope of one
skill in the art. A suitable means may be any high shear device so
as to obtain a desired droplet (and corresponding microcapsule
particle) size within the range from about 1 to about 200 .mu.m.
Preferably the droplet size is from about 3 to about 150 .mu.m, and
most preferably from about 5 to about 120 .mu.m. Once the desired
droplet size is obtained, the dispersion means is discontinued.
Only mild agitation is required for the remainder of the process.
The organic phase comprises the solid water-soluble, biologically
active compound suspended in the substantially water-immiscible
liquid to be encapsulated prepared as described above in steps 1
and 2. The aqueous phase comprises water and at least one
emulsifier and/or protective colloid.
[0036] Suitably the core also comprises a water-immiscible
liquid.
[0037] Suitably the hydrophobic material is a wax.
[0038] Suitably the core is fully or partially solid; more suitably
it is partially solid. Clearly there is a relationship between the
particle size of the solid agrochemical and the particle size of
the microcapsules; in order to obtain control over the release rate
of the biologically active compound, the VMD ratio of the particle
size of this compound to that of the microcapsules will be
typically of the value 1:5; suitably in the range 1:3 to 1:100;
more suitably 1:5 to 1:20.
[0039] In order to obtain the microcapsules, the organic phase
and/or the aqueous phase must contain one or more materials which
can react to form a polymer. In one preferred embodiment, the
organic phase contains at least one diisocyanate and/or
polyisocyanate, whilst the aqueous phase contains at least one
diamine and/or polyamine. In the situation where at least one
diamine and/or polyamine is included in the aqueous phase, this
component is added to the aqueous phase after the formation of the
oil-in-water emulsion as described above in step 3.
Step 4--at least one diamine and/or polyamine is added to the
oil-in-water emulsion through the aqueous phase, maintaining mild
agitation throughout. This part of the process may be conducted at
a temperature above the melting point of the hydrophobic solid (or
mixture of hydrophobic solid with suitable water-immiscible
liquid). In one embodiment, however, the reaction product at this
stage of the process can be cooled (by a range of techniques) and
thereafter a reactive monomer added to the cooled reaction mixture.
This cooling at this stage of the process allows the meltable
hydrophobic solid to solidify. In one embodiment, an oil soluble or
water-dispersible isocyanate may be added at this stage and allowed
to equilibrate onto the surface of the solidified emulsion.
Thereafter, a further reactant (such as a diamine) can be added.
Stirring is continued typically for 30 minutes to 3 hours until the
formation of the capsule polymer wall is complete. The reaction
temperature is generally in the range from about 20.degree. C. to
about 80.degree. C. In the situation where approximately equimolar
amounts of isocyanate and amino groups are present, the reaction
temperature is preferably from about 20.degree. C. to about
60.degree. C., and even more preferably from about 20.degree. C. to
about 40.degree. C. In the situation where an excess of isocyanate
groups are present, the reaction temperature is preferably from
about 30.degree. C. to about 60.degree. C., and even more
preferably from about 40.degree. C. to about 50.degree. C. Reaction
times in excess of 3 hours combined with temperatures of 60.degree.
C. or above are not recommended; such conditions have been utilised
for the encapsulation of suspensions of water-insoluble compounds
(US 2003/0119675 and JP 2000247821) but it has been found that such
conditions are not suitable for the formation of the microcapsules
of this invention, as they result in poor encapsulation efficiency
(the water-solubility of the active compounds increases with
increasing temperature, resulting in excessive quantities of the
active compound transferring into the aqueous phase).
[0040] This invention includes solid agrochemicals. Where the term
water-soluble as used when referring to the solid agrochemcial to
be encapsulated, this is defined as a water-solubility in the range
of 0.1-100 g/l, preferably in the range 0.5-50 g/l, at 20.degree.
C. This may be any such compound from the group comprising
pharmaceuticals and agrochemicals such as insecticides, herbicides,
fungicides, acaricides, rodenticides, molluscicides and plant
growth regulators.
[0041] Suitable herbicides include 2,3,6-TBA, 2,4-D,
2-chloro-6'-ethyl-N-isopropoxymethylaceto-o-toluidide, acifluorfen,
alachlor, ametryn, amicarbazone, amidosulfuron, asulam,
azimsulfuron, benazolin, benfuresate, bensulfuron-methyl,
bentazone, bromacil, carbetamide, chloridazon, chlorimuron-ethyl,
chlorsulfuron, cinosulfuron, clomazone, cloransulam-methyl,
cyanizine, cyclosulfamuron, dicamba, dichlorprop, dichlorprop-P,
diflufenzopyr, dimethachlor, dimethipin, diphenamid,
ethametsulfuron-methyl, ethoxysulfuron, fenoxaprop-P,
flazasulfuron, florasulam, flucetosulfuron, flumioxazin,
fluometuron, flupyrsulfuron-methyl-sodium, fluoroxypyr, fomesafen,
foramsulfuron, halosulfuron-methyl, haloxyfop-P,
imazamethabenz-methyl, imazamox, imazapic, imazapyr, imazethapyr,
imazasulfuron, iodosulfuron-methyl-sodium, isouron, MCPA, MCPB,
mecoprop, mecoprop-P, mesosulfuron-methyl, mesotrione, metamitron,
metazachlor, methyldymron, metosulam, metoxuron, metribuzin,
metsulfuron-methyl, monolinuron, naptalam, oxasulfuron, penoxsulam,
pethoxamid, primisulfuron-methyl, prometon, propachlor, propanil,
propham, propoxycarbazone-sodium, prosulfuron, pyroxyfen,
quinmerac, rimsulfuron, simetryn, sulcotrion, sulfentrazone,
sulfometuron-methyl, sulfosulfuron, tebuthiuron, tepraloxydim,
terbacil, terbumeton, thifensulfuron-methyl, tralkoxydim,
triasulfuron, tribenuron-methyl, triclopyr and
trisulfuron-methyl.
[0042] Suitable fungicides include 2-phenylphenol, azaconazole,
azoxystrobin, carboxin, cymoxanil, cyproconazole, dodemorph
acetate, dodine, epoxyconazole, etridiazole, fenfuram, ferimzone,
flusilazole, flutriafol, fuberidazole, furalaxyl, furametpyr,
imazalil, metalaxyl, methasulfocarb, metominostrobin, myclobutanil,
ofurace, oxadixyl, oxycarboxin, phenylmercury acetate,
propiconazole, prothioconazole, pyrimethanil, pyroquilon,
tetraconazole, thiabendazole and tricyclazole.
[0043] More suitable fungicides include 2-phenylphenol,
azaconazole, carboxin, cymoxanil, dodemorph acetate, dodine,
etridiazole, fenfuram, ferimzone, flusilazole, flutriafol,
fuberidazole, furalaxyl, furametpyr, imazalil, metalaxyl,
methasulfocarb, metominostrobin, myclobutanil, ofurace, oxadixyl,
oxycarboxin, phenylmercury acetate, prothioconazole, pyrimethanil,
pyroquilon, tetraconazole; thiabendazole and tricyclazole.
[0044] Suitable insecticides include abamectin, acetamiprid,
aldicarb, azadirachtin, azamethiphos, bendiocarb, carbaryl,
carbofuran, clothianidin, cryolite, dazomet, dimethylvinphos, DNOC,
emamectin benzoate, ethiofencarb, ethylene dibromide, fenamiphos,
fenobucarb, fipronil, flonicamid, imidacloprid, isoprocarb,
lufenuron, methidathion, methyl isothiocyanate, metlocarb,
pirimicarb, propoxur, pymetrozine, pyridaphenthion,
chloranthraniliprole (Renaxapyr.TM.), sabadilla, spinosad,
sulcofuron-sodium, thiacloprid, thiamethoxam, thiofanox,
triazamate, XMC and xylylcarb.
[0045] More suitable insecticides include acetamiprid, aldicarb,
azadirachtin, azamethiphos, bendiocarb, carbaryl, carbofuran,
clothianidin, cryolite, dazomet, dimethylvinphos, DNOC,
ethiofencarb, ethylene dibromide, fenamiphos, fenobucarb, fipronil,
flonicainid, imidacloprid, isoprocarb, methidathion, methyl
isothiocyanate, metlocarb, pirimicarb, propoxur, pymetrozine,
pyridaphenthion, sabadilla, spinosad, sulcofuron-sodium,
thiacloprid, thiamethoxam, thiofanox, triazamate, XMC and
xylylcarb.
[0046] Suitable rodenticides include chloralose, chlorophacinone,
coumatetralyl and strychnine.
[0047] Suitable molluscicides include metaldehyde and
niclosamide.
[0048] Suitable plant growth regulators include 1-naphthylacetic
acid, 4-indol-3-ylbutyric acid, ancymidol, cloxyfonac,
ethychlozate, flurprimidol, gibberellic acid, indol-3-ylacetic
acid, maleic hydrazide, mefluidide, prohexadione-calcium and
trinexapac-ethyl.
[0049] Particularly suitable insecticides are the neonicotinoids
such as acetamiprid, clothianidin, imidacloprid, thiacloprid and
thiamethoxam. An especially suitable insecticide is
thiamethoxam.
[0050] In a further aspect, the present invention provides use of a
product to combat or control an agricultural pest which comprises
applying to the pest or to a locus of the pest, a pesticidally
effective amount of the product. The pests may include [fungal]
diseases, insects and weeds. Suitably the pest is a termite.
[0051] The concentration of the solid agrochemical is suitably from
0.1-80%, more suitably 0.1-70% [most suitably 0.1-65%] by weight of
the microcapsule.
[0052] For those cases in which the solid agrochemical is suspended
in a substantially water-immiscible liquid, said liquid may be any
liquid which does not dissolve the compound to any appreciable
extent but is a sufficiently good solvent to form a solution with
the hydrophobic solid above the melting point of the hydrophobic
solid. Suitably the water-solubility of the liquid under ambient
conditions [typically 20.degree. C.] is approximately 5000 ppm by
weight or less.
[0053] Suitable examples of such liquids are aromatic organic
compounds such as xylenes or naphthalenes, eg. Solvesso.RTM. 200;
aliphatic organic compounds such as allkyl esters, eg. Exxate.RTM.
700--Exxate.RTM. 1000, Prifer.RTM. 6813; paraffinic compounds, eg.
the Nolpar.RTM. & Isopar.RTM. ranges of solvents; alkyl
phthalates, such as diethyl phthalate, dibutylphthalate and
dioctylphthalate; alcohols, such as isopropyl alcohol; ketones,
such as acetophenone and cyclohexanone; mineral oils, eg.
Cropspray.RTM. 7N or 11N; vegetable or seed oils, such as rapeseed
oil; and alkylated seed oils. The liquid may be a mixture of more
than one compound.
[0054] Furthermore the liquid in which the agrochemical is
suspended may in itself be or comprise a second biologically active
compound. Moreover, the hydrophobic solid with a melting point
above 25 C may also be a second (or more) biologically active
compound The phase volumes of the disperse organic phase and the
continuous aqueous phase may be varied within a wide range;
typically the organic phase is present at 5 to 70% by weight;
suitably from 15 to 70% by weight; and more suitably from 15 to 50%
by weight based on the entire formulation.
[0055] The hydrophobic meltable solid with a melting point greater
than or equal to 25 C is the means by which a matrix can be
produced to retain the solid agrochemical more effectively within a
microcapsule. This meltable solid should not display a glass
transition temperature so that it is effectively not a polymer.
Such products encompass the use of waxes with a melting point above
ambient temperature (25.degree. C.). This meltable hydrophobic
solid can be a single component or derived form mixtures of
products designed to produce a desired melting point. This will
include combinations with water immiscible liquids or low melting
point hydrophobic solids that produce a mixture with a reduced
melting point. These include waxes, C26 and higher, paraffin waxes,
cholesterol, fatty alcohols, such as cetyl alcohol, mono-, di- and
triglycerides of animal and vegetable origin such as tallow,
hydrogenated fat, hydrogenated castor oil, fat derivatives such as
fatty acids, soaps, esters, hydrophobic starches such as ethyl
cellulose, lecithin, metal soaps of fatty acids such as zinc,
calcium or magnesium stearate, palmitate or oleate.
[0056] The waxes may be of natural origin, meaning they may be
animal, vegetable or mineral. Animal waxes include beeswax,
lanolin, shellac wax and Chinese insect wax. Vegetable wax includes
carnauba, candelilla, bayberry and sugar cane waxes. Mineral waxes
include fossil or earth waxes including ozokerite, ceresin and
montan or petroleum waxes, including paraffin and microcrystalline
waxes. Alternatively the waxes may be synthetic or mixtures of
natural and synthetic waxes. For instance, these can include low
molecular weight partially oxidised polyethylene, which can be
preferentially co-melted with paraffin.
[0057] The fatty derivatives may be either fatty acids, fatty
metallic salts of these fatty acids, fatty acid amides, fatty
alcohols and fatty esters or mixtures of these. In particular, the
acid may be a carboxylic acid and the salts may be calcium,
magnesium, zinc or aluminium salts. The acid amide may be
stearamide.
[0058] Sterols or long chain sterol, esters may also be such as
cholesterol or ergosterol. Preferred compounds are waxes such as
hydrogenated castor oil, lanolin, beeswax and mixtures of vegetable
oils and waxes such as the product PB3 .TM.. To determine the
preferred composition of the organic phase (either a complete wax
or mixture of wax and water-immiscible liquid), phase diagrams can
be easily constructed of the likely components to determine optimal
melting points for the composite organic phase. Such compositions
may be solid solutions of wax in an oil, eutectic mixtures or even
mixtures where the wax and water-immiscible oil are homogeneous
above the melting point of the hydrophobic solid but on cooling the
hydrophobic solid separates from the water immiscible liquid to
produce domains of solid hydrophobic material that can introduce a
tortuous path to retard the release of a solid agrochemical from
the ultimate microcapsule. In a specific embodiment, the water
immiscible liquid (and separately the hydrophobic meltable solid)
may be an agrochemical or the hydrophobic organic phase in which
the solid agrochemical is dispersed can be a eutectic mixture or
solid solution of at least one meltable agrochemical in combination
with a second component that may be a water immiscible liquid and
which may separately also be an agrochemical.
[0059] The liquid (held above the melting point of the hydrophobic
meltable solid) containing the solid agrochemical suitably contains
a dispersant. The exact choice of dispersant(s) will depend on the
choice of solid and the liquid but particularly suitable
dispersants are those which act by steric hindrance and are active
only at the solid/organic liquid interface and do not act as
emulsifying agents. Such dispersants are suitably made up of (i) a
polymeric chain having a strong affinity for the liquid and (ii) a
group which will adsorb strongly to the solid.
[0060] Examples of dispersants which may be used in microcapsules
containing a solid biologically active compound suspended in a
liquid [and which are generally polymeric] are given in WO
95/13698, and include products available under the tradenames
Hypermer.RTM., Atlox.RTM., Agrimer.RTM. and Solsperse.RTM..
[0061] In general, the range of dispersant concentration used is
from about 0.01 to about 10% by weight based on the organic phase,
but higher concentrations may also be used.
[0062] For the successful encapsulation of suspensions of solid
agrochemical according to the present invention the choice of the
liquid/dispersant combination within the microcapsules is
particularly critical. Suitable systems include Solvesso.RTM. 200
and Solsperse.RTM. 117000; rapeseed oil and Solsperse.RTM. 17000; a
Norpar.RTM. 15/Prifer.RTM. 6813 mixture with Z190-165.TM.; and
Cropspray.RTM. 7N or 11N with a one or more dispersants selected
from Atlox.RTM. 4912, Atlox.RTM. LP1, Agrimer.RTM. AL22 and
Agrimer.RTM. AL30. Such combinations are particularly suitable when
the biologically active compound is thiamethoxam.
[0063] In general, the surfactant or surfactants in the aqueous
phase of the microcapsule suspension are selected from anionic,
cationic and non-ionic surfactants with an HLB range from about 10
to about 16 that is high enough to form a stable oil-in-water
emulsion; non-ionic surfactants are particularly suitable. If more
than one surfactant is used, the individual surfactants may have
HLB values lower than 10 or higher than 16. However, when combined
together the overall HLB value of the surfactants may be in the
range 10-16. Suitable surfactants include polyethylene glycol
ethers of linear alcohols, ethoxylated nonylphenols,
tristyrylphenol ethoxylates, block copolymers of propylene oxide
and ethylene oxide, and polyvinyl alcohols. Polyvinyl alcohols are
particularly suitable.
[0064] In general, the range of surfactant concentration in the
process is from about 0.01 to about 10% by weight, based on the
aqueous phase, but higher concentrations of surfactant may also be
used.
[0065] Additionally, a protective colloid may also be present in
the aqueous phase. This must adsorb strongly onto the surface of
the oil (molten) droplets. Suitable protective colloids include
polyalkylates, methyl cellulose, polyvinyl alcohols, mixtures of
polyvinyl alcohols and gum arabic, and polyacrylamides. Polyvinyl
alcohols are particularly suitable.
[0066] There should be sufficient colloid present to afford
complete coverage of the surfaces of all the droplets of the molten
organic liquid. The amount of protective colloid employed will
depend on various factors, such as molecular weight and
compatibility. The protective colloid may be added to the aqueous
phase prior to the addition of the organic phase, or can be added
to the overall system after the addition of the organic phase or
the dispersion of it. The protective colloid is generally present
in the aqueous phase in an amount of from about 0.1 to about 10% by
weight of the aqueous phase.
[0067] Where separate emulsifiers and colloid stabilisers are used
in the aqueous phase, the emulsifier should not displace the
protective colloid from the surface of the droplets of the organic
liquid.
[0068] In one preferred embodiment, the organic phase contains at
least one diisocyanate and/or polyisocyanate, whilst the aqueous
phase contains at least one diamine and/or polyamine.
[0069] Any diisocyanate or polyisocyanate, or mixtures thereof, may
be employed, provided that it is soluble in the liquid chosen for
the organic phase. Where aromatic liquids are used, aromatic
isocyanates such as isomers of tolylene diisocyanate, isomers and
derivatives of phenylene diisocyanate, isomers and derivatives of
biphenylene diisocyanates, and/or
polymethylenepolyphenyleneisocyanates (PMPPI) are suitable. Where
aliphatic liquids are used, aliphatic isocyanates are suitable, for
example aliphatic acyclic isocyanates such as
hexamethylenediisocyanate (HMDI), cyclic aliphatic isocyanates such
as isophoronediisocyanate (IPDI) or 4,4'methylenebis(cyclohexyl
isocyanate), and/or trimers of HMDI or IPDI and the like. Polymeric
polyisocyanates, biurets, blocked polyisocyanates, and mixtures of
polyisocyanates with melting point modifiers may also be used. MDI
is a particularly preferred polyisocyanate. Should other properties
be desired from the isocyanate such as increased flexibility, then
pegylated derivatives may be employed wherein part of the
isocyanate is reacted with a suitable polyol. Such techniques and
chemistries are well known in the art. In one embodiment, the
isocyanate may be added directly to a cooled (and therefore
solidified) emulsion of a solid agrochemical dispersed in a
hydrophobic solid. The isocyanate is allowed to equilibrate with
the solidified emulsion before addition of further reactants (such
as a diamine).
[0070] The concentration of the isocyanate(s), and the ratio(s)
where more than one isocyanate is used, is/are chosen so as to
obtain the desired release rate profile for the particular end
application. The concentration of the isocyanate(s) must also be
high enough to form a (non-continuous) matrix dispersed throughout
the microcapsules. In general, the isocyanate(s) will comprise from
about 5 to about 75%, more suitably from about 7 to about 30%, even
more suitably from about 10 to about 25% and most suitably from
about 10 to about 20%, by weight of the microcapsule.
[0071] The diamine or polyamine, or mixtures thereof, may be any
such compound(s) which is/are soluble in the aqueous phase.
Aliphatic or alicyclic primary or secondary diamines or polyamines
are very suitable, such as ethylene-1,2-diamine,
diethylenetriamine, triethylenetetramine,
bis-(3-aminopropyl)-amine, bis-(2-methylaminoethyl)-methylamine,
1,4-diaminocyclohexane, 3-amino-1-methylaminopropane,
N-methyl-bis-(3-aminopropyl)amine, 1,4-diamino-n-butane,
1,6-diamino-n-hexane and tetraethylenepentamine. Polyethyleneimines
are also suitable.
[0072] The molar ratio of amine moieties to isocyanate moieties may
be varied from about 0.1:1 to about 1.5:1. Suitably either (i)
approximately equimolar concentrations of amine and isocyanate
moieties are employed, with the molar ratio of amine to isocyanate
moieties ranging from about 0.8:1 to about 1.3:1, in which case the
wall formation reaction is suitably carried out at a temperature
above the melting point of the hydrophobic solid or, when a
separate cooling step in introduced to the process to reduce the
temperature to below the melting point of the hydrophobic solid,
from about 20.degree. C. to about 40.degree. C., even more
preferably from about 20.degree. C. to about 30.degree. C.; or (ii)
a significant excess of isocyanate is present, with the ratio of
amine to isocyanate moieties ranging from about 0.1:1 to about
0.35:1, in which case the wall formation reaction is preferably
carried out at a temperature from about 30.degree. C. to about
60.degree. C., even more preferably from about 40.degree. C. to
about 50.degree. C.
[0073] Other wall chemistries may be used, for example
polyurethanes and polyamides, by appropriate selection of wall
forming components. Suitable glycols for addition through the
aqueous phase include those taught above and which are water
soluble. These may also include simple polyhydroxylic glycols, for
example, suitable diols are ethylene glycol, 1,2-butanediol,
diethylene glycol, triethylene glycol, polyalkylene glycols, such
as polyethylene glycol, and also 1,2- and 1,3-propanediol,
1,4-butanediol, 1,6-hexanediol, neopentyl glycol or neopentyl
glycol hydroxypivalate. Examples of polyols having 3 or more
hydroxyl groups in the molecule, which may be used additionally, if
desired, include trimethylolpropane, trimethylolethane, glycerol,
erythritol, pentaerythritol, di-trimethylolpropane,
dipentaerythritol, thimethylol-benzene and trishydroxyethyl
isocyanurate. Higher functionality may be employed by use of the
various sugars such as fructose, dextrose, glucose and derivatives
thereof. Mixtures of water soluble and oil soluble reactive
hydroxyl containing compounds are also contemplated. Polyamides may
be produced in a similar manner by selection of an appropriate acid
feedstock (such as sebacoyl chloride). Mixtures, in any ratio, of
polyureas, polyurethanes and polyamides are also part of the
present invention.
[0074] Therefore suitably the polymeric shell is a polymer which is
a polyurea, a polyamide or a polyurethane or is a mixture of two or
more of these polymers; more suitably it is a polyurea.
[0075] In a similar manner, oil soluble amines may be contemplated
as being added to the oil phase prior to preparation of the aqueous
dispersion and thereafter a suitable water dispersible isocyanate
reactant may be added to complete the interfacial reaction.
[0076] In another aspect, the present invention provides a process
of making a product as herein described comprising the steps
(i) melting the hydrophobic material to form a hydrophobic liquid;
(ii) dispersing the agrochemical in the hydrophobic liquid; (iii)
emulsifying the hydrophobic liquid into an aqueous phase; (iv)
optionally cooling the resultant emulsion; (v) causing an
interfacial polymerisation reaction to occur at the interface
between the hydrophobic liquid and the aqueous phase to produce a
capsule suspension; and (vi) optionally allowing or causing the
capsule suspension to cool.
[0077] Suitably the process comprises the step of rapidly cooling
an emulsion to below the melting point of the hydrophobic
material.
[0078] Suitably the process involves a step where an isocyanate is
introduced through the aqueous phase.
[0079] By selection of microcapsule size, isocyanate chemistry and
concentration, amine identity and the ratio of different isocyanate
monomers and/or amines when more than one isocyanate monomer and/or
amine is present, the release rate of the solid agrochemical can be
varied from a half-life [T50; the time taken for 50% of the active
ingredient to be lost from the capsule (i.e. released)] value of a
few hours up to several months or years. It is surprising that such
a wide range of release rates is achievable for a solid
agrochemical, and it is particularly unexpected that extremely slow
release rates into an aqueous sink are obtained.
[0080] Furthermore, mixtures of microcapsules with different
release rates may be combined in a single formulation, to provide a
tailored release profile.
[0081] The capsule compositions, as produced, will be dispersions
in water. These microcapsules may be post-formulated, to stabilise
them for long term shelf life storage, with anti-settling agents,
which include water-soluble polysaccharides such as xanthan gum,
water-insoluble polysaccharides such as microcrystalline cellulose
and structured clays such as bentonites. Microcrystalline cellulose
is a particularly suitable anti-settling agent.
[0082] Furthermore, it is possible to add additional agrochemicals
to the aqueous phase, either as solids, emulsions (either as an
emulsion of a compound that is liquid at ambient temperature or as
an emulsion of a solution of an agrochemical in a suitable
essentially water immiscible solvent) or as a solution in water or
mixtures of the above. The agrochemical added directly to the
external aqueous phase may be the same compound as within the
microcapsule.
[0083] Therefore suitably the aqueous phase comprises an
agrochemical. Suitably an agrochemical in the aqueous phase has a
water-solubility in the range of 0.1 to 100 g/l at 20.degree. C.;
more suitably it is a neonictinoid insecticide; even more suitably
it is acetamiprid, clothianidin, imidacloprid, thiacloprid or
thiamethoxam; and most suitably it is thiamethoxam.
[0084] Where an additional agrochemical is present in the aqueous
phase, the concentration of this compound may be varied within a
relatively wide range. Generally the concentration of this compound
will be between 0 and 50% by weight, based on the total aqueous
phase.
[0085] Furthermore, it is possible to dry such water based
compositions. This can be achieved by concentration of the water
based composition (e.g. sedimentation, centrifugation) followed by
a suitable drying technique such as drum drying. It may also be
achieved by techniques such as spray-drying [including fluid bed
agglomeration techniques and similar granulation processes] or, if
the compounds are heat sensitive, freeze drying or atmospheric
freeze drying. Spray drying techniques are preferred as they are
fast and may conveniently be applied to dispersions such as the
microcapsules of this invention. Production of dry product from a
water based dispersion usually requires the addition of further
inert components to protect the integrity of the capsules during
the drying stage, or during storage and also to allow easy complete
re-dispersion of the dry product back into water for application.
Such inerts include, but are not limited to, essentially water
soluble film-forming agents such as polyvinyl alcohols,
polyvinylpyrrolidones and polyacrylic acids. Other ingredients may
include surfactants, dispersants, sugars, lignosulfonates,
disintegrants such as cross-linked polyvinylpyrrolidones and
maltodextrins.
[0086] The dried products moreover, may contain other agrochemicals
that are not encapsulated as described above for the solid
agrochemical.
[0087] It is also possible to use a dried product directly without
dilution into water. Such use may be as a granular product in rice
cultivation, for use on cultivated turf and also as a feedstock for
blending into fertiliser mixtures for subsequent application to
soil, turf or other targets such as rice.
[0088] Suitably the dry product is granular.
[0089] Suitably the dry product is water-dispersible.
[0090] The wide range of release rates achievable with the
technology of the present invention allows exploitation in several
applications, including traditional crop protection outlets both as
a foliar or a soil applied product, for use on cultivated turf, as
a seed treatment and numerous other applications such as protection
against termites and as a long-lasting residual spray for general
pest control.
[0091] In a still further aspect of the invention there is provided
the use of a composition as described herein for the protection of
industrial materials [referred to as "materials protection"].
Suitably the industrial material to be protected is selected from
the group consisting of: wood; plastic; wood plastic composite;
paint; paper; and wallboards. The protection may be in the form of
a product that deters, repels or kills an attack of a target, such
as in the area of termite protection, or house protection against
invasive insect species, a barrier can be places between the
article to be protected (eg a building) and the external
environment in which the pest species normally resides.
[0092] The term "Industrial Material" includes those materials used
in construction and the like. For example, Industrial Material may
be structural timber, doors, cupboards, storage units, carpets,
particularly natural fibre carpets such as wool and hessian,
plastics, wood (including engineered wood) and wood plastic
composite.
[0093] In a particular embodiment the Industrial Material is a
coating. "Coating" includes compositions applied to a substrate,
for example, paints, stains, varnishes, lacquers, primers,
semi-gloss coatings, gloss coatings, flat coatings, topcoats,
stain-blocking coatings, penetrating sealers for porous substrates,
concrete, marble, elastomeric coatings, mastics, caulks, sealants,
board and panelling coatings, transportation coatings, furniture
coatings, coil coatings, bridge and tank coatings, surface marking
paints, leather coatings and treatments, floor care coatings, paper
coatings, personal care coatings [such as for hair, skin or nails],
woven and non-woven fabric coatings, pigment printing pastes,
adhesive coatings [such as, for example, pressure sensitive
adhesives and wet- or dry-laminating adhesives] and plaster.
[0094] Suitably "coating" means paint, varnish, stain, lacquer or
plaster; more suitably "coating" is a lacquer or alternatively
"coating" may mean paint. Paint may comprise, for example, a film
former and a carrier (which carrier can be water and/or an organic
solvent) and optionally a pigment.
[0095] In addition to this, "Industrial Material" includes
adhesives, sealants, joining materials, joints and insulation
material.
[0096] "Wood" is to be understood to include wood and wood
products, for example: derived timber products, lumber, plywood,
chipboard, flakeboard, laminated beams, oriented strandboard,
hardboard, particle-board, tropical wood, structural timber, wooden
beams, railway sleepers, components of bridges, jetties, vehicles
made of wood, boxes, pallets, containers, telegraph-poles, wooden
fences, wooden lagging, windows and doors made of wood, plywood,
chipboard, joinery, or wooden products which are used, quite
generally, for building houses or decks, in building joinery or
wood products that are generally used in house-building including
engineered wood, construction and carpentry.
[0097] "Industrial Material" also includes wallboards such as
gypsum based wallboards.
[0098] In a still further aspect of the invention there is provided
"Industrial Materials" comprising a composition as herein
described. In a particular embodiment said Industrial materials are
selected from the group consisting of: wood; wood plastic
composite; paint; paper; and wallboards. In a particular embodiment
said Industrial materials comprise wood. Examples of ways in which
an Industrial Material can be treated with a product according to
the invention are: by including said product in the Industrial
Material itself, absorbing, impregnating, treating (in closed
pressure or vacuum systems) said material with said fungicide,
dipping or soaking the building material, or coating the building
material for example by curtain coating, roller, brush, spray,
atomisation, dusting, scattering or pouring application.
[0099] The use of slow releasing microcapsules allows for an
extended period of biological control compared to non-encapsulated
formulations, and for soil applied products the extent of leaching
may also be reduced by the use of such microcapsules; the latter is
particularly relevant for those active compounds with appreciable
water solubility disclosed within this invention, whereby their
substantial water solubility renders them prone to leaching when
applied in an non-encapsulated form. In the particular embodiment
where the microcapsules are suspended in an aqueous medium
comprising a suspension of non-encapsulated agrochemical, both
rapid knockdown activity and an extended period of biological
control may be achieved, particularly for insecticides. Other
utilities include incorporation of such products into materials
where a slow release of a water soluble material is desired, such
as for treatment of water bodies and addition to centre pivot
irrigation systems where high volumes of water rapidly leach active
materials.
[0100] The microcapsule suspensions thus produced may be utilized
in the normal fashion of such products, i.e. by packaging the
suspension and ultimately transferring the suspension into a spray
tank or other spray equipment, in which it is mixed with water to
form a sprayable suspension. A range of application techniques may
be utilised for the soil application of such microcapsules,
including pre-planting and post-planting applications either as a
dilute spray or as a more concentrated drench, including direct
application into the planting hole. Application may also be made to
seedling trays etc. prior to transplant. For termite protection,
the microcapsules of this invention may be applied as a soil drench
underneath the foundations, as a perimeter `trench and treat`
barrier around the outside of the foundations, or applied directly
onto concrete. Alternatively, the suspension of microcapsules may
be converted into a dry microcapsule product by spray drying or
other known techniques and the resulting material packaged in dry
form.
[0101] It will be appreciated that there are many aspects to the
present invention. In one aspect, it relates to a product
comprising microcapsules which themselves comprise
(a) a polymeric shell; and (b) a core which comprises an
agrochemical which has a melting point above 25.degree. C.
characterised in that the agrochemical is dispersed as a solid in a
hydrophobic material which has a melting point greater than or
equal to 25.degree. C. but which does not exhibit a glass
transition temperature.
[0102] Further aspects and preferences are given below. Throughout
this invention, where the term "water immiscible liquid" is
employed this also includes hydrophobic meltable solids above their
melting point and mixtures of such hydrophobic solids (above their
melting point) with water immiscible liquids
[0103] A microcapsule formulation in which microcapsules comprise a
solid agrochemical dispersed in a (non-continuous) matrix which is
at least partially solid and which is distributed throughout the
microcapsules, in which the microcapsules are suspended in an
aqueous phase during their formation.
[0104] A microcapsule formulation as described above wherein
agrochemical is a solid at ambient temperature and is dispersed in
an organic non-solvent within the capsules.
[0105] A microcapsule formulation as described above and a process
as described above for making it in which a monomer is present in
the disperse phase and is caused to undergo polymerisation to form
the (non-continuous) matrix.
[0106] A microcapsule formulation as described above wherein a
water immiscible liquid is a vinyl containing reactive-monomer.
[0107] A microcapsule formulation as described above and a process
as described above for making it in which the solid agrochemical is
dispersed within a liquid in which a reagent is dissolved, and in
which the liquid and reagent are caused to react to form the
(non-continuous) matrix.
[0108] A microcapsule formulation as described above wherein a
water immiscible liquid is a reactant with a second reactive
species by which a (non-continuous) matrix is formed.
[0109] A microcapsule formulation as described above in which the
solid agrochemical is dispersed within a substantially
water-immiscible liquid which is retained within the micro
capsule.
[0110] A microcapsule formulation as described above in which the
solid agrochemical is dispersed within a material which is held
above its melting point during processing, and is subsequently
allowed to solidify.
[0111] A microcapsule formulation as described above wherein the
water immiscible liquid is a solid at ambient temperature and the
process is operated above the melting point of the water immiscible
liquid, forming a matrix on cooling below the melting point. For
example, when using a wax to form a matrix.
[0112] A microcapsule formulation as described above in which the
substantially water-immiscible liquid is or comprises a second
agrochemical.
[0113] A microcapsule formulation as described above in which one
or more agrochemical(s) is/are present in the continuous aqueous
phase [either as a solid dispersion, a liquid dispersion or as a
solution in the aqueous phase].
[0114] A microcapsule formulation as described above in which the
solid agrochemical which is present in the continuous aqueous phase
is the same solid agrochemical as the one which is dispersed in the
microcapsules.
[0115] A microcapsule formulation as described above in which the
pesticide is thiamethoxam.
[0116] The use of a microcapsule formulation as described above to
control the release rate of a pesticide thereby providing an
extended period of biological control.
[0117] The use of a microcapsule formulation as described above to
control the release rate of a pesticide thereby providing a
reduction in leaching of the pesticide.
[0118] A microcapsule formulation as described above wherein the
formulation is water based (capsules dispersed in water).
[0119] A microcapsule formulation as described above where the
formulation is a dry product, produced by a drying process such as
spray drying or freeze drying or by a suitable concentration
procedure and final drying.
[0120] A microcapsule formulation as described above where a
(non-continuous) matrix-forming compound (suitably a polymer) is
caused to separate within the microcapsule by removal of a volatile
solvent for that compound.
[0121] The use of a microcapsule formulation as described above to
improve safety of an agrochemcial either to the manufacturer, user,
or the environment.
[0122] A process for forming a microcapsule formulation as
described above in which the (non-continuous) matrix is prepared
either before the capsule, during capsule preparation or after
capsule preparation.
[0123] A process for forming a microcapsule formulation as
described above in which the (non-continuous) matrix is formed by
an interfacial polycondensation reaction.
[0124] A process as described above in which at least one reagent
for the polycondensation reaction is present in the dispersed
[organic] phase and at least one reagent for the polycondensation
reaction is present in the continuous [aqueous] phase.
[0125] A process as described above in which the reagents for the
polycondensation reaction are only present in the dispersed
phase.
[0126] The following examples are given by way of illustration and
not by way of limitation of the invention, in which many capsule
samples are characterised by their VMD [Volume Median
Diameter].
EXAMPLES 1a-1j
[0127] The following examples demonstrate that thiamethoxam can be
suspended in a meltable hydrophobic solid, followed by
encapsulation within a polyurea wall, wherein isocyanate moieties
for the formation of the polyurea wall are dissolved in the
meltable hydrophobic solid. Such formulations are not trivial to
prepare successfully due to the high water-solubility of
thiamethoxam (4.1 g/l at 20.degree. C.) which means there is a
tendency for the particles of thiamethoxam to migrate into the
aqueous phase during the emulsification process and/or before the
meltable hydrophobic solid has solidified and the formation of the
microcapsule wall is complete. Preventing excessive migration of
thiamethoxam particles into the aqueous phase is particularly
challenging for this type of formulation due to the elevated
temperatures employed during the emulsification process.
[0128] Thiamethoxam was encapsulated using the following process
according to the recipes given in Table 1. Initially thiamethoxam
(re-ground in an air jet mill or similar) was dispersed into a
meltable hydrophobic solid (wax) in the presence of an oil-soluble
dispersant; this dispersion was carried out using high shear at a
temperature typically 10-20.degree. C. above the melting point of
the meltable hydrophobic solid. An isocyanate was subsequently
dissolved into the thiamethoxam suspension. This suspension was
then emulsified into an aqueous solution of polyvinyl alcohol
(emulsification being carried out at temperature typically
10-20.degree. C. above the melting point of the wax). Additional
water was added to reduce the temperature of the emulsion, and
rapid cooling was effected by immersion of the emulsion in an
ice/water bath (maintaining agitation throughout). An aqueous
solution of a polyfunctional amine was added immediately after
initiation of the cooling process, and cooling was continued until
the wax had solidified. The resultant capsule formulations were
characterised by their VMDs.
[0129] Paraffin wax (melting point 53-57.degree. C.) and beeswax
(synthetic, melting point 61-65.degree. C.) are supplied by
Aldrich.
[0130] Lanolin (melting point 38-44.degree. C.) is supplied by
Acros.
[0131] PB3.TM. (melting point 38-44.degree. C.) is a blend of
vegetable oil and hydrogenated vegetable oil supplied by
Aarhus.
[0132] Docosane (melting point 42.degree. C.) is available from
Sigma-Aldrich.
[0133] Solvesso.RTM. 100 is an aromatic hydrocarbon solvent
supplied by Exxon.
[0134] Rapeseed oil (from Brassica rapa) was sourced from
Fluka.
[0135] Cropspray.RTM. 7N is a mineral oil supplied by Sun Oil
Company.
[0136] Agrimer.RTM. AL22 and AL30 are alkylated vinylpyrrolidone
copolymers supplied by ISP.
[0137] Solsperse.RTM. 17000 is a polymeric dispersant supplied by
Lubrizol.
[0138] Desmodur.RTM. Z4470 is the trimer of isophoronediisocyanate
supplied by Bayer as a 70% solution in naphtha 100.
[0139] Desmodur.RTM. W is 4,4'-methylenebis(cyclohexyl isocyanate)
supplied by Bayer.
[0140] Gohsenol.RTM. GL05 is a polyvinylalcohol supplied by Nippoii
Gohsei.
TABLE-US-00001 TABLE 1 Component (% w/w) 1a 1b 1c 1d 1e 1f
Thiamethoxam 10 10 10 10 10 10 Agrimer AL-30 0.8 0.8 0.8 0.8 0.8
0.8 Beeswax 9.2 9.2 9.2 -- -- -- Lanolin -- -- -- 9.2 9.2 9.2
Desmodur Z4470 SN 1.5 3.2 7.1 1.5 3.2 7.1 Gohsenol GL05 2.7 2.7 2.7
5.4 5.4 5.4 Diethylenetriamine 0.16 0.33 0.74 0.16 0.33 0.74 Water
(for emulsification) 44 44 44 41.3 41.3 41.3 Water (for cooling) To
100% To 100% To 100% To 100% To 100% To 100% VMD (.mu.m) 31.7 29.0
39.7 22.1 23.6 20.14 Component (% w/w) 1g 1h 1i 1j Thiamethoxam 10
10 10 10 Agrimer AL-30 0.8 0.8 0.8 0.8 PB3 9.2 9.2 9.2 -- Paraffin
wax -- -- -- 9.2 Desmodur Z4470 SN 1.5 3.2 7.1 -- Desmodur W -- --
-- 2.2 Gohsenol GL05 2.7 2.7 2.7 2.7 Diethylenetriamine 0.16 0.33
0.74 0.64 Water (for emulsification) 44 44 44 44 Water (for
cooling) To 100% To 100% To 100% To 100% VMD (.mu.m) 21.1 28.2 19.7
84.1
EXAMPLES 2a-2c
[0141] The following examples demonstrate that a meltable
hydrophobic solid contained within the capsules may consist of a
mixed wax/solvent system.
[0142] Thiamethoxam was encapsulated according to the recipes given
in Table 2 using the same methodology as in Examples 1, but with
the additional step of dissolving a solvent in the suspension of
thiamethoxam in wax prior to emulsification.
TABLE-US-00002 TABLE 2 Component (% w/w) 2a 2b 2c Thiamethoxam 9.1
9.1 9.1 Agrimer AL-30 0.73 0.73 0.73 PB3 -- -- 8.37 Paraffin wax
8.37 -- -- Beeswax -- 8.37 -- Solvesso 100 1.7 1.7 1.7 Desmodur
Z4470 SN 3.2 3.2 3.2 Gohsenol GL05 2.7 2.7 2.7 Diethylenetriamine
0.33 0.33 0.33 Water (for emulsification) 44 44 44 Water (for
cooling) To 100% To 100% To 100% VMD (.mu.m) 63.3 36.9 25.8
EXAMPLES 3a-3b
[0143] The following examples demonstrate that a meltable
hydrophobic solid contained within the capsules may consist of a
mixed wax/solvent system; in these examples the internal content of
the capsules comprises a mixture of millbases, in each of which
thiamethoxam had been dispersed prior to mixing of the
millbases.
[0144] Thiamethoxam was encapsulated using the following process
according to the recipes given in Table 3. A finely ground
suspension of thiamethoxam in a substantially water immiscible
solvent was mixed with a suspension of thiamethoxam in a wax at a
temperature above the melting point of the wax. Encapsulation was
then carried out according to the process described in Examples
1.
TABLE-US-00003 TABLE 3 Component (% w/w) Millbase 1 Millbase 2
Millbase 3 3a 3b Thiamethoxam 50 50 50 -- -- Agrimer AL-30 4 -- --
-- -- Agrimer AL-22 -- 5 -- -- -- Solsperse 17000 -- -- 5 -- --
Lanolin 46 -- -- -- -- Cropspray 7N -- 45 -- -- -- Rapeseed oil --
-- 45 -- -- Millbase 1 -- -- -- 16 12 Millbase 2 -- -- -- 4 --
Millbase 3 -- -- -- -- 8 Desmodur W -- -- -- 2.2 -- Desmodur Z4470
SN -- -- -- -- 3.2 Gohsenol GL05 -- -- -- 5.4 5.4
Diethylenetriamine -- -- -- 0.64 0.33 Water (for emulsification) --
-- -- 41.3 41.3 Water (for cooling) -- -- -- To 100% To 100% VMD
(.mu.m) -- -- -- 10.7 15.0
EXAMPLE 4
[0145] The following example demonstrates that thiamethoxam can be
suspended in a wax, followed by encapsulation within a polyurea
wall, wherein the isocyanate moieties for the formation of the
polyurea wall are added to an aqueous emulsion of the dispersed
thiamethoxam in wax after solidification of the wax. This example
also uses a novel cooling method which allows a higher
concentration of thiamethoxam to be obtained in the final
formulation.
[0146] Thiamethoxam was encapsulated using the following process
according to the recipe given in Table 4. Initially thiamethoxam
(pre-ground in an air jet mill or similar) was dispersed into the
wax in the presence of an oil-soluble dispersant; this dispersion
was prepared using high shear at a temperature typically
10-20.degree. C. above the melting point of the wax. This
dispersion (suspension) was then emulsified into an aqueous
solution of polyvinyl alcohol (emulsification being carried out at
temperature typically 10-20.degree. C. above the melting point of
the wax). The emulsion was then cooled rapidly to below the melting
point of the wax by the addition of carbo-ice to the emulsion,
stirring throughout with a low shear mixer.
[0147] Once the emulsion was at ambient temperature, an isocyanate
was added under low shear stirring.
[0148] After 35 minutes, an aqueous solution of a polyfunctional
amine was added still under stirring.
TABLE-US-00004 TABLE 4 Example 4 Thiamethoxam 13.73 technical
Agrimer AL30 1.10 Docosane 12.63 Gohsenol GL05 3.66 Water (for To
100% emulsification) Desmodur W 6.4 Diethylene triamine 2.1 VMD
(.mu.m) 10.0
EXAMPLE 5
[0149] The following example demonstrates that the microcapsules
prepared according to examples 1-3 are stable upon high temperature
storage.
[0150] Formulations prepared according to examples 1-3 were stored
for up to 3 weeks at 50.degree. C., during which they showed
essentially no changes in particle size; the results are given in
Tables 5 & 6 below.
TABLE-US-00005 TABLE 5 Example 1a 1b 1c 1d 1e 1f Initial VMD
(.mu.m) 31.7 29.0 39.7 22.1 23.6 20.14 VMD after 3 weeks storage
32.6 27.9 37.1 24.6 24.8 23.8 at 50.degree. C. (.mu.m)
TABLE-US-00006 TABLE 6 Example 1g 1h 1i 2a 2c 3b Initial VMD
(.mu.m) 21.1 28.2 19.7 63.3 25.8 15.0 VMD after 1 weeks storage
21.7 29.3 20.8 63.5 26.3 16.9 at 50.degree. C. (.mu.m)
EXAMPLE 6
[0151] This example demonstrates that seed treatments comprising
encapsulated suspensions of thiamethoxam in a wax show extended
control of release of thiamethoxam compared to unencapsulated
thiamethoxam in the form of Cruiser.TM. 5FS (a suspension
concentrate containing 500 g/l thiamethoxam).
[0152] Encapsulated suspensions of thiamethoxam in wax were mixed
with a coating polymer
[0153] Spectrum.TM. 300 C and applied to maize seeds in a seed
treater so as to give a loading of 1.25 mg thiamethoxam and 0.625
mg Spectrum 300 C per seed.
[0154] Ten treated seeds were placed on approximately 80 g soil in
a Buchner funnel (pore size 2, 11 cm diameter) and covered with an
additional 35 g soil and a filter paper. Fixed amounts of water
were sprayed onto the filter paper, and the eluent was collected,
weighed and analysed for thiamethoxam content. The release rate
data obtained is shown in FIG. 1.
* * * * *