WO2011003961A2

WO2011003961A2 - Formulations comprising terpolymer and active substance, preparation and use thereof

Info

Publication number: WO2011003961A2
Application number: PCT/EP2010/059767
Authority: WO
Inventors: Chi Wu; Jing Dreher; Uwe Kardorff; Weidong He; Guangzhao Zhang
Original assignee: Basf Se
Priority date: 2009-07-10
Filing date: 2010-07-08
Publication date: 2011-01-13
Also published as: WO2011003240A1; WO2011003961A3

Abstract

The invention relates to a formulation comprising a terpolymer and active substance (D), characterized in that said terpolymer comprises main chain segment (A), hydrophobic pendent chains (B), and hydrophilic pendent chains (C). The invention also relates to processes for the preparation of the formulation and a ready-for-use formulation comprising the inventive formulation.

Description

Formulations Comprising Terpolymer and Active Substance, Preparation and Use Thereof

Field of the invention

The present invention relates to a type of formulations comprising a terpolymer and an active substance, preparation thereof, and the use thereof in the preparation of ready-for-use formulations.

Background of the invention

Many types of active substances are ideally used as aqueous formulations (mainly as aqueous solutions or aqueous dispersions) in various fields. For example, in the field of plant protection, active substances such as insecticides, acaricides, nematicides, fungicides and herbicides as well as growth regulators are frequently formulated and sold as concentrates, such as aqueous concentrates or as concentrates in organic solvent, for example suspensions or emulsions, and also as solid concentrates, such as powders, dusts or granules. These formulations, before their application, are generally diluted to the desired application concentration by addition of a large amount of water. Also, pharmaceutically and cosmetically active substances and food additives, as well as active substances used in biological field, such as vitamins, provitamins, proteins, RNA and DNA and the like, are also generally formulated into formulations in aqueous medium for transportation and/or usage. Thus, it is necessary for the active substances to be effectively stable or dissolved in aqueous.

However, the main problems are that, many active substances have low solubility, i.e., generally less than 10 g/l at 23°C/1 atm. (1013 mbar). When these active substances are formulated into aqueous formulations or aqueous ready-for-use formulations, they form unstable heterogeneous systems in which the active substance is present as emulsified or dispersed phase in a continuous aqueous phase. The active substances tend to separate out of the system, for example by crystallization or creaming or sedimentation. This reduces the availability of the active substance, resulting in low utilization of the active substance. Moreover, for purpose of proper me- tering of the active substance, it is also desirable to have a stable system in which the active substance is homogeneously distributed.

To solve these problems, conventional methods, such as lyophilization, utilization of various surfactant and/or emulsifier and/or dispersant, have been generally used to stably distribute the active substance in aqueous formulation or aqueous ready-for-use formulations, in order to obtain a stable system and to avoid formation of large aggregate or droplet of active substance, and to enhance the utilization of the active substance. However, such conventional measures are typically unsatisfactory. The separation of the active substance, for example creaming or sedimentation of the active substance, may still occur, in particular if the aqueous formulation is stored for a relatively long time at elevated temperature and/or at highly variable temperatures or in the vicinity of the freezing point. This problem is particularly significant if the active substance has a tendency to crystallize. WO2008/040786 disclosed a comb-copolymer, and the use of the comb-copolymer in stabilizing the aqueous phase that contains an insoluble or slightly soluble active substance, to obtain a stable aqueous formulation. The comb-copolymer is used as dispersant for dispersing and stabilizing the active substances that have been divided into small size, in water.

However, in the prior art, when polymer is used to prepare stable aqueous formulations of water insoluble or slightly soluble active substances, generally, said polymer is synthesized first, then such polymer is mixed with an active substance under certain conditions. In a formulation formed from the polymer and water insoluble or slightly soluble active substances, generally the interaction between the active substances and the polymer is weak, such that it is difficult for the active substances to be dispersed into the polymer matrix, in particular in the case of high level of loading of the active substances. Thus, in order to obtain the stability of the final formulation, the loading level of water insoluble or slightly soluble active substance in the formulation is significantly limited. The amount of active substance in given amount of stable formulation is very low. In addition, as the polymer has to be formed first, then mixed with active substance, the preparation process of the formulation according to the prior art is complicated, and is economically undesirable.

Surprisingly, the present invention solved the problems in the prior art by synthesizing a terpo- lymer and preparing a formulation based on the visco-elastic behavior of the macromolecule. In the formulations of the invention, there is a strong interaction between the inventive terpolymer and the active substance, thus for a given amount of formulation of the present invention, the loading level of the active substance can be substantively increased. The introduction of hydrophilic component in the terpolymer can shorten the interaction time among dispersed mic- roparticles. More importantly, the introduction of hydrophobic component and a proper chain extension, not only the formation of the dispersed microparticles is induced and promoted, but also the relaxation time of the chains inside each microparticle is prolonged. With the change of the preparation conditions, different formulation forms such as emulsion or suspension are obtained, and the dispersion state of the formulations can be adjusted when the formulation is dilu- ted with substantive amount of water. With these measures, the relaxation time of the chains inside the dispersed phase can be made much longer than the interaction time between the dispersed phases. In other words, within the relatively shorter interaction time, the dispersed phase is in glassy state which prevents aggregation, and thus enables the formation of a stable formulation system. The formulations can be prepared with simple procedures and easy to apply.

Detailed description of the invention

Formulation

In one aspect, the invention relates to a formulation comprising terpolymer and active substance (D), said terpolymer comprises main chain segment (A), hydrophobic pendent chains (B), and hydrophilic pendent chains (C). For purpose of facilitating better understanding of the present invention, the formulation according to the invention is described as comprises core-shell particles formed by the terpolymer and the active substances (D), wherein the hydrophilic pendent chains (C) forms said shell, the hydrophobic pendent chains (B) forms said core, and said main chain segment (A) of the terpo- lymer combines with said active substance (D), and said active substance (D) is encapsulated between said core and said shell. However, the invention is not to be limited by this description. In other words, the said core-shell structure is only provided for the convenience of describing and understanding the invention, not for limiting the invention in any way. The formulation according to the invention comprises usually an organic solvent. Preferred organic solvents are those which are used in the process according to the invention, such as those listed below. Preferably, said solvent is able to dissolve all the reactant involved in the reactions and active substance (D), and essentially inert to the reactions. Said solvent preferably comprises ester of lower aliphatic carboxylic acid with lower aliphatic alcohol. Suitable esters of lower aliphatic carboxylic acid with lower aliphatic alcohol are C2-C8 aliphatic carboxylic acid with Ci-Cs aliphatic alcohol. Preferred solvents are ethyl acetate and butyl acetate. The formulation may comprise from 1 to 99 wt% organic solvent, preferably from 40 to 90 wt%.

The formulation according to the invention comprises preferably less than 5 wt% water, more preferably less than 1 wt% and in particular less than 0.1 wt% water.

The formulation according to the invention comprises the active substance (D) preferably in dissolved or dispersed form. More preferably, the active substance (D) is present in dissolved or emulsified form, in particular in dissolved form. The formulation according to the invention comprises typically from 0.1 to 60 wt% active substance (D), preferably from 1 to 30 wt%, and more preferably from 5 to 18 wt%.

Preferably, the formulation according to the invention is obtainable by the process according to the invention. In particular, the formulation according to the invention is obtained by the process according to the invention.

Terpolymer

Structure of the inventive terpolymer comprises main chain segment (A), hydrophobic pendent chains (B) and hydrophilic pendent chains (C). The main chain segment (A) can be either hydrophobic or hydrophilic, depending on the condition. The molecular weight of the inventive terpolymer is at least 100,000 g/mol, preferably at least 150,000 g/mol, more preferably at least 200,000 g/mol, and at most 4,000,000 g/mol, preferably at most 3,000,000 g/mol, more preferably at most 2,000,000 g/mol, most preferably at most 1 ,000,000 g/mol. In a preferred embodiment of the invention, the molecular weight of the inventive terpolymer is 1 ,300,000g/mol. In the present invention, the main chain segment (A) interacts with the active substance (D) to weaken the aggregation tendency of the active substance (D), in particular the tendency of se- parating, crystallizing, flocculating or precipitating out of the system, so as to enables the formation of stable formulations.

In the present invention, preferably an environment sensitive component is used as the main chain segment (A), i.e., the main chain segment (A) will change its property (such as being hydrophilic or hydrophobic) under different conditions (such as changing in temperature and pH value). For example, the main chain segment (A) of the terpolymer which is formed with monomer (a) is hydrophobic under low pH conditions and may combine with the active substance (D), while being hydrophilic at high pH conditions and may release the active substance (D). This property of main chain segment (A) will help encapsulating said active substance (D) in the stable formulations under certain conditions, while releasing the active substance from the stable formulation under other conditions.

In general, said main chain segment (A) is derived from monomer (a), said hydrophobic pen- dent chain (B) is derived from monomer (b), and said hydrophilic pendent chain (C) is derived from monomer (c).

In a preferred embodiment of the present invention, monomers (a), (b) and (c) are copolymeri- zed to form the inventive terpolymer. After the polymerization, the functional groups contained in monomer (a) will constitute the main chain segment (A) which in turn will complex with the active substance (D), while monomers (b) and (c) copolymerized into the main chain segment (A), and the groups contained in monomers (b) and (c) form the pendent chain (B) and (C) respectively. In this embodiment, pendent chains (B) and (C) are attached to the main chain segment (A) during the formation of the main chain segment (A).

Monomer (a) that contributes to the formation of the main chain segment (A) can be a member selected from the group consisting of (meth)acrylic acids, vinyl benzene sulfonic acid, vinyl pyridine, and N-isopropyl acrylamide, and the like. In a preferred embodiment, monomer (a) is selected from the group consisting of acrylic acid, methacrylic acid and vinyl benzene sulfonic a- cid, more preferably from acrylic acid and methacrylic acid. The aforemententioned monomers may be used anlone or in mixture with one another.

Monomer (b) that contributes to the formation of the hydrophobic pendent chain (B) can be for example a hydrophobic vinyl monomer, such as alkyl (meth)acrylate, styrene and/or vinyl aceta- te. When alkyl (meth)acrylate is used as monomer (b), the number of the carbon atom in the alkyl group is at least 8, preferably at least 10, more preferably at least 12, and at most 30, preferably at most 24, more preferably at most 20, and most preferably 18. In a preferred embodiment, monomer (b) is selected from the group consisting Cs-3o-alkyl (meth)acrylate, styrene and vinyl acetate, more preferably from the group consisting of Ci2-24-alkyl (meth)acrylate. The afo- remententioned monomers may be used anlone or in mixture with one another. Monomer (c) that contributes to the formation of the hydrophobic pendent chain (C) can be a member selected from the group consisting of for example (polyethylene glycol monomethyl- ether) acrylate (i.e., MPEG acrylate), acrylamide, vinylpyrrolidone, and N,N-dimethylacrylamide. In a preferred embodiment, monomer (c) is selected from the group consisting (polyethylene glycol monomethylether) acrylate. When (polyethylene glycol monomethylether) acrylate (i.e., MPEG acrylate) is used as Monomer (c), the molecular weight of the polyethylene glycol unit is at least 500g/mol, preferably at least 1000g/mol, and up to 8000g/mol, preferably up to l OOOOg/mol. In another embodiment, monomer (c) is selected from (polyethylene glycol mono-Ci-Ci2- alkylether) (meth)acrylate, (polyethylene glycol) (meth)acrylate, acrylamide, vinylpyrrolidone, and N,N-dimethylacrylamide. Preferably, monomer (c) is selected from (polyethylene glycol mo- no-Ci-Ci2-alkylether) (meth)acrylate and (polyethylene glycol) (meth)acrylate. In particular, monomer (c) is selected from (polyethylene glycol mono-Ci-Ci2-alkylether) (meth)acrylate.

The aforemententioned monomers may be used anlone or in mixture with one another. The molecular weight of the polyethylene glycol unit is at least 500g/mol, preferably at least

1000g/mol, and up to 8000g/mol, preferably up to 100u0g/mol.

The term "terpolymer" according to the invention does not exclude the presence of a small a- mount of other structures such as other hydrophobic pendent chains other than the hydrophobic pendent chain (B). One example of said other hydrophobic pendent chains is the ones that are derived from di(meth)acrylates.

With acrylic acid, Ciβ acrylate and PEG acrylate being used as monomers (a), (b) and (c), respectively, the terpolymer of the present invention can be illustrated as following.

(a) (b) (C)

In a further preferred embodiment, the hydrophobic pendent chain (B) and the hydrophobic pendent chain (C) constitute the chain of the terpolymer together with the main chain segment (A). In the inventive terpolymer, the ratios between main chain segment (A), the hydrophobic pendent chain (B) and the hydrophilic pendent chain (C) influence the formation of hydrophobic core structure and hydrophilic shell structure as well as the loading of active substance (D) in said core-shell structure. Preferably in the inventive terpolymer, the amount of the main chain segment (A) is 17-60% by weight, the amount of the hydrophobic pendent chain (B) is 20-56% by weight, and the amount of the hydrophilic pendent chain (C) is 20-40% by weight, all based on the total weight of the terpolymer. Furthermore, based on the total weight of the terpolymer, less than 1.5% by weight of a di(meth)acrylate can be further added as a comonomer, such as ethylene glycol di(meth)acrylate, butylene glycol di(meth)acrylate, diethylene glycol

di(meth)acrylate, or polyethylene glycol di(meth)acrylate.

In another embodiment the amount of the main chain segment (A) in the termpolymer is at least 10 wt%, more preferably at least 25 wt%, in particular at least 35 wt%, all based on the total weight of the terpolymer. In another embodiment the amount of the main chain segment (A) in the termpolymer is up to 80 wt%, more preferably up to 65 wt%, in particular up to 55 wt%, all based on the total weight of the terpolymer.

In another embodiment the amount of the hydrophobic pendent chain (B) in the termpolymer is at least 10 wt%, more preferably at least 25 wt%, in particular at least 35 wt%, all based on the total weight of the terpolymer. In another embodiment the amount the hydrophobic pendent chain (B) in the termpolymer is up to 70 wt%, more preferably up to 55 wt%, in particular up to 45 wt%, all based on the total weight of the terpolymer.

In another embodiment the amount of the hydrophilic pendent chain (C) in the termpolymer is at least 10 wt%, more preferably at least 25 wt%, in particular at least 35 wt%, all based on the total weight of the terpolymer. In another embodiment the amount of the hydrophilic pendent chain (C) in the termpolymer is up to 60 wt%, more preferably up to 45 wt%, in particular up to 40 wt%, all based on the total weight of the terpolymer.

In another embodiment the amount of the di(meth)acrylate in the termpolymer is at least 0.01 wt%, more preferably at least 0.1 wt%, all based on the total weight of the terpolymer. In a- nother embodiment the amount of the di(meth)acrylate in the termpolymer is up to 5 wt%, more preferably up to 2 wt%, all based on the total weight of the terpolymer.

The structural unit of monomer (b) is randomly distributed along the main chain of the terpoly- mer. In case the Monomer (b) is an alkyl (meth)acrylate, each of the structural unit has a hydrocarbon type pendent chain of preferably more than 12 carbon atoms, more preferably each of the structural unit has a hydrocarbon type pendent chain of 12 -24 carbon atoms, more preferably 18 carbon atoms.

Active substance (D)

Active substances in the sense of the present invention are defined as substances that can manifest a particular activity or function or reactive under particular circumstance. The terms "active substance" and "effect substance" are used interchangeably and are synonymous in the context of this patent application. Examples of suitable active substance include small molecule active substance such as insecticides, acaricides, nematicides, fungicides and herbicides and growth regulators, and high molecular weight active substance such as proteins, RNA and DNA. Moreover, the inventive terpolymer can also be used to disperse and stabilize functional inorganic compounds, such as quantum-dots, as well as magnetic, light-emitting and catalytic substances, into polymeric core-shell particles. In another preferred embodiment, the active substance is a pesticide. The term pesticides refers to at least one active substance selected from the group of the fungicides, insecticides, nematicides, herbicides, safeners and/or growth regulators. Preferred pesticides are fungicides, insecticides, herbicides and growth regulators. Especially preferred pesticides are growth regulators. Mixtures of pesticides of two or more of the abovementioned classes may also be used. The skilled worker is familiar with such pesticides, which can be found, for example, in the Pesticide Manual, 15th Ed. (2009), The British Crop Protection Council, London. Suitable insecticides are insecticides from the class of the carbamates, organophosphates, organochlorine insecticides, phenylpyrazoles, pyrethroids, neonicotinoids, spinosins, avermectins, milbemycins, juvenile hormone analogs, alkyl halides, organotin compounds nereistoxin analogs, benzoylureas, dia- cylhydrazines, METI acarizides, and insecticides such as chloropicrin, pymetrozin, flonicamid, clofentezin, hexythiazox, etoxazole, diafenthiuron, propargite, tetradifon, chlorofenapyr, DNOC, buprofezine, cyromazine, amitraz, hydramethylnon, acequinocyl, fluacrypyrim, rotenone, or their derivatives. Suitable fungicides are fungicides from the classes of dinitroanilines, allylamines, anilinopyrimidines, antibiotics, aromatic hydrocarbons, benzenesulfonamides, benzimidazoles, benzisothiazoles, benzophenones, benzothiadiazoles, benzotriazines, benzyl carbamates, carbamates, carboxamides, carboxylic acid diamides, chloronitriles cyanoacetamide oximes, cya- noimidazoles, cyclopropanecarboxamides, dicarboximides, dihydrodioxazines, dinitrophenyl crotonates, dithiocarbamates, dithiolanes, ethylphosphonates, ethylaminothiazolecarboxamides, guanidines, hydroxy-(2-amino)pyrimidines, hydroxyanilides, imidazoles, imidazolinones, inorga- nic substances, isobenzofuranones, methoxyacrylates, methoxycarbamates, morpholines,

N-phenylcarbamates, oxazolidinediones, oximinoacetates, oximinoacetamides, peptidylpyrimi- dine nucleosides, phenylacetamides, phenylamides, phenylpyrroles, phenylureas, phosphona- tes, phosphorothiolates, phthalamic acids, phthalimides, piperazines, piperidines, propionami- des, pyridazinones, pyridines, pyridinylmethylbenzamides, pyrimidinamines, pyrimidines, pyri- midinonehydrazones, pyrroloquinolinones, quinazolinones, quinolines, quinones, sulfamides, sulfamoyltriazoles, thiazolecarboxamides, thiocarbamates, thiophanates, thiophenecarboxami- des, toluamides, triphenyltin compounds, triazines, triazoles. Suitable herbicides are herbicides from the classes of the acetamides, amides, aryloxyphenoxypropionates, benzamides, benzofu- ran, benzoic acids, benzothiadiazinones, bipyridylium, carbamates, chloroacetamides, chloro- carboxylic acids, cyclohexanediones, dinitroanilines, dinitrophenol, diphenyl ether, glycines, imidazolinones, isoxazoles, isoxazolidinones, nitriles, N-phenylphthalimides, oxadiazoles, oxa- zolidinediones, oxyacetamides, phenoxycarboxylic acids, phenylcarbamates, phenylpyrazoles, phenylpyrazolines, phenylpyridazines, phosphinic acids, phosphoroamidates, phosphorodithioa- tes, phthalamates, pyrazoles, pyridazinones, pyridines, pyridinecarboxylic acids, pyridinecarbo- xamides, pyrimidinediones, pyrimidinyl(thio)benzoates, quinolinecarboxylic acids, semicarbazo- nes, sulfonylaminocarbonyltriazolinones, sulfonylureas, tetrazolinones, thiadiazoles, thiocarba- mates, triazines, triazinones, triazoles, triazolinones, triazolocarboxamides, triazolopyrimidines, triketones, uracils, ureas.

For the purpose of the present invention, slightly soluble means a solubility of the active substance (e.g. the pesticide) in water of less than 10 g/l, usually of less than 5 g/l and in particular of less than 1 g/l and especially of less than 0.1 g/l, at 25⁰C and 1 atm (1013 mbar).

Manner of Incorporation

In the present invention, the interaction between the main chain segment (A) and the active substance (D) is strong that hinders the aggregation tendency of the active substance (D). E- xamples of such interaction include hydrogen bond, charge interaction, hydrophobicity interaction, etc.

The particle with core-shell structure formed according to the invention has the particle size and particle size distribution of from hundreds nanometers to tens of microns, more frequently from hundreds nanometers to several microns.

Loading of active substance (D) in the formulation according to the invention can be up to about

350% by weight based on the polymer used, and up to about 200mg/ml based on the solvent used.

Preparation process of the formulation

Another aspect of the present invention relates to a process for the preparation of the inventive formulation. In a preferred embodiment of the present invention, said process include the steps of: a1 ) Dissolving monomers (a), (b) and (c) and active substance (D) in a solvent,

a2) In-situ copolymerization of monomers (a), (b) and (c) into the terpolymer in the presence of the solvent and the active substance (D), producing the inventive formulation comprising the terpolymer and the active substance (D).

The appearance of the obtained formulation can be clear and transparent, or can be a milky colloid. The reaction type involved in above process is not critical to the implementation of the present invention. They can be any of commonly known reaction type, such as radical polymerization. Various known initiators can be used in the polymerization, such as azo initiator, peroxide initia- tor and redox initiating system. Reaction temperature can be determined by those skilled in the art. In a preferred embodiment, the lower limit of the reaction temperature used in polymerization is O⁰C, preferably 2O⁰C, more preferable 3O⁰C, while the upper limit is 100⁰C, preferably 8O⁰C, more preferably 7O⁰C, particular preferably 6O⁰C. Solvent used in the process of the present invention is important for the implementation of the present invention. Preferably, said solvent is able to dissolve all the reactant involved in the reactions and active substance (D), and essentially inert to the reactions. The solvent has usually a water content of less than 5 wt%, preferably less than 1 wt%, and in particular less than 0.1 wt%. Said solvent preferably comprises ester of lower aliphatic carboxylic acid with lower aliphatic alcohol. Suitable esters of lower aliphatic carboxylic acid with lower aliphatic alcohol are C2-C8 aliphatic carboxylic acid with Ci-Cs aliphatic alcohol. Preferred solvents are ethyl acetate and butyl acetate. pH vale of inventive formulation is preferably from about 1 to about 5.

Molar ratio of monomer (a) : monomer (b) : monomer (c) : active substance (D) in step a2) can be determined by a skilled person through experiments. Typically, the molar ratio may be deducted from the ratios by weight between the main chain segment (A), the hydrophobic pendent chain (B) and the hydrophilic chein (C) as mentioned above.

With the process of the present invention, stably dispersed inventive formulation could be obtained directly. For example, the formulation can be readily used after dilution with 2 to 100 times by weight, preferably 50-100 times by weight, with water. The formulation according to the invention is preferably an agrochemical formulation, which comprises at least one pesticide. The agrochemical compositions may also comprise auxiliaries which are customary in agrochemical compositions. The auxiliaries used depend on the particular application form and active substance, respectively. Examples for suitable auxiliaries are solvents, solid carriers, dispersants or emulsifiers (such as further solubilizers, protective col- loids, surfactants and adhesion agents), organic and anorganic thickeners, bactericides, anti- freezing agents, anti-foaming agents, if appropriate colorants and tackifiers or binders (e. g. for seed treatment formulations).

Suitable solvents are water, organic solvents such as mineral oil fractions of medium to high boiling point, such as kerosene or diesel oil, furthermore coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, e. g. toluene, xylene, paraffin, tetra- hydronaphthalene, alkylated naphthalenes or their derivatives, alcohols such as methanol, ethanol, propanol, butanol and cyclohexanol, glycols, ketones such as cyclohexanone and gamma-butyrolactone, fatty acid dimethylamides, fatty acids and fatty acid esters and strongly polar solvents, e. g. amines such as N-methylpyrrolidone. Solid carriers are mineral earths such as silicates, silica gels, talc, kaolins, limestone, lime, chalk, bole, loess, clays, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground synthetic materials, fertilizers, such as, e. g., ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas, and products of vegetable origin, such as cereal meal, tree bark meal, wood meal and nutshell meal, cellulose powders and other solid car- riers.

Suitable surfactants (adjuvants, wtters, tackifiers, dispersants or emulsifiers) are alkali metal, alkaline earth metal and ammonium salts of aromatic sulfonic acids, such as ligninsoulfonic acid (Borresperse^® types, Borregard, Norway) phenolsulfonic acid, naphthalenesulfonic acid (Mor- wet^® types, Akzo Nobel, U.S.A.), dibutylnaphthalene-sulfonic acid (Nekal^® types, BASF, Germany), and fatty acids, alkylsulfonates, alkylarylsulfonates, alkyl sulfates, laurylether sulfates, fatty alcohol sulfates, and sulfated hexa-, hepta- and octadecanolates, sulfated fatty alcohol glycol ethers, furthermore condensates of naphthalene or of naphthalenesulfonic acid with phenol and formaldehyde, polyoxy-ethylene octylphenyl ether, ethoxylated isooctylphenol, octyl- phenol, nonylphenol, alkylphenyl polyglycol ethers, tributylphenyl polyglycol ether, tristearyl- phenyl polyglycol ether, alkylaryl polyether alcohols, alcohol and fatty alcohol/ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropyl- ene, lauryl alcohol polyglycol ether acetal, sorbitol esters, lignin-sulfite waste liquors and proteins, denatured proteins, polysaccharides (e. g. methylcellulose), hydrophobically modified starches, polyvinyl alcohols (Mowiol^® types, Clariant, Switzerland), polycarboxylates (Sokolan^® types, BASF, Germany), polyalkoxylates, polyvinylamines (Lupasol^® types, BASF, Germany), polyvinylpyrrolidone and the copolymers therof.

Examples for thickeners (i. e. compounds that impart a modified flowability to compositions, i. e. high viscosity under static conditions and low viscosity during agitation) are polysaccharides and organic and anorganic clays such as Xanthan gum (Kelzan^®, CP Kelco, U.S.A.), Rhodo- pol^® 23 (Rhodia, France), Veegum^® (R.T. Vanderbilt, U.S.A.) or Attaclay^® (Engelhard Corp., NJ, USA). Bactericides may be added for preservation and stabilization of the composition. Examples for suitable bactericides are those based on dichlorophene and benzylalcohol hemi formal (Proxel^® from ICI or Acticide^® RS from Thor Chemie and Kathon^® MK from Rohm & Haas) and isothia- zolinone derivatives such as alkylisothiazolinones and benzisothiazolinones (Acticide^® MBS from Thor Chemie).

Examples for suitable anti-freezing agents are ethylene glycol, propylene glycol, urea and glycerin. Examples for anti-foaming agents are silicone emulsions (such as e. g. Silikon^® SRE, Wacker, Germany or Rhodorsil^®, Rhodia, France), long chain alcohols, fatty acids, salts of fatty acids, fluoroorganic compounds and mixtures thereof. Examples for tackifiers or binders are polyvinylpyrrolidone, polyvinylacetates, polyvinyl alcohols and cellulose ethers (Tylose^®, Shin- Etsu, Japan).

Ready-for-use formulation comprising the inventive formulation

The present invention also relates to a ready-for-use formulation comprising the formulation according to the invention. Usually, the ready-for-use formulation comprises at least 20 wt% water, more preferably at least 50 wt% and in particular at least 70 wt%.

The present invention also relates to a process for the preparation of a ready-for-use formulation comprising the inventive formulation, said process including the step of mixing the inventive formulation with water, preferably with 2 to 100 times by weight, more preferably with 50-100 times by weight of water.

In a preferred embodiment of the present invention, during the formation of the ready-for-use formulation, with the changing of the conditions (for example changing of pH value by way of water dilution), property of main chain segment (A) changes, thus achieving the goal of relea- sing the active substance (D).

Examples

The present invention is further illustrated by the following examples. These examples are for illustrative purpose only and can not be used to limit the scope of the present invention.

Example 1. Preparation of the formulation of the present invention

Epoxiconazole (EP), MPEG acrylate (polyethylene glycol monomethyl ether acrylate, M_n 2000 g/mol), methacrylic acid (MAA), octodecyl acrylate (ODA) and azo-bis-isobutyronitrile (AIBN) were added into ethyl acetate (30 ml.) according to the concentration as shown in Table 1 respectively, and homogenized with agitation. After that, a small amount of ethylene dimethac- rylate (EDMA) was added to the polymerization mixture and the copolymerization was performed at 6O⁰C under nitrogen atmosphere for 24 h. The procedure was repeated five times with the changing of the amount of epoxiconazole (EP) to obtain test samples A-E of the formulation. Table 1 shows the compositions of the formulations, which were clear solutions after polymerization.

Table 1 : Dispersion copolymerization of MAA, ODA, MPEG acrylate and EDMA (C_EDMA = 0.6 mg/mL) in the presence of different amounts of epoxiconazole (CEP)

Amount of ethylene dimethacrylate was 0.5 g/ml.

Example 2. Preparation of the formulation of the present invention

Epoxiconazole (EP), MPEG acrylate, methacrylic acid (MAA), octodecyl acrylate (ODA) and azo-bis-isobutyronitrile (AIBN) were added into ethyl acetate (20 ml) according to the concentration as shown in Table 2, and homogenized with agitation. The reaction was performed at 60 0C under nitrogen atmosphere for 24 h. The procedure was repeated with the changing of the amount of MAA to obtain test samples A, B and C of the formulation. Table 2 shows the composition of the formulation after polymerization, which were milk-like emulsions.

Table 2. Dispersion copolymerization of MAA, PEG acrylate and ODA

Example 3. Reparation of ready-for-use formulation of the present invention

Under magnetic stirring, the samples listed in Table 2 were added dropwise into distillated water at the volume ratio of the sample to water of 1 :100. Appearance of each thinned re-dispersion was a milk-like emulsion. Immediately after dilution and 5 h after dilution while storing at room temperature there was no difference observed in the milk-like emulsion. This proves the good stability of the ready-for-use formulation.

Claims

1. A formulation comprising a terpolymer and an active substance (D), characterized in that said terpolymer comprises main chain segment (A), hydrophobic pendent chains (B), and hydrophilic pendent chains (C).

2. The formulation according to claim 1 , characterized in that the main chain segment (A) is hydrophilic or hydrophobic under different environmental conditions.

3. The formulation according to claims 1 or 2, characterized in that the main chain segment (A) is formed from monomer (a) which is selected from the group consisting of

(meth)acrylic acid, vinyl benzene sulfonic acid and N-isopropyl acrylamide.

4. The formulation according to any of claims 1 to 3, characterized in that the hydrophobic pendent chain (B) is derived from monomer (b) which is a hydrophobic vinyl monomer.

5. The formulation according to claim 4, characterized in that the monomer (b) is selected from alkyl (meth)acrylate, styrene and/or vinyl acetate.

6. The formulation according to any of claims 1 to 5, characterized in that the hydrophilic pendent chain (C) is derived from monomer (c) which is selected from the group consisting of (polyethylene glycol monomethylether) acrylate, acrylamide, vinylpyrrolidone, and N, N- dimethylacrylamide.

7. The formulation according to any of claim 1 to 6, characterized in that, in the terpolymer, the amount of the main chain segment (A) is 17-60% by weight, the amount of the hydrophobic pendent chain (B) is 20-56% by weight, and the amount of the hydrophilic pendent chain (C) is 20-40% by weight, all based on the total weight of the terpolymer.

8. The formulation according to any of claims 1 to 7, characterized in that the structural unit of monomer (b) forming the hydrophobic pendent chain (B) is randomly distributed along the main chain of the terpolymer, and each of the structural unit has hydrocarbon type pendent chain of more than 12 carbon atoms, preferably each of the structural unit has a hydrocarbon type pendent chain of 12 -18 carbon atoms.

9. The formulation according to any of claims 1 to 8, characterized in that the active substance (D) has a solubility in water of less than 10 g/l at 25⁰C and 1 atm (1013 mbar).

10. The formulation according to any of claims 1 to 9, characterized in that the small molecule active substance is selected from the group consisting of insecticides, fungicides, and herbicides; the high molecular weight active substance is selected from the group consisting of proteins, RNA and DNA; and the functional inorganic compounds is selected from the group consisting of quantum-dots, magnetic substance, light-emitting substance and catalytic substances.

1 1. A process for the preparation of the formulation according any one of claims 1-10, charac- terized in that the process include the steps of:

a1) dissolving monomers (a), (b) and (c) and active substance (D) in the solvent, a2) in-situ copolymerization of monomers (a), (b) and (c) into a terpolymer in the presence of the solvent and the active substance (D), producing the formulation comprising terpolymer and the active substance (D).

12. The process according to claim 11 , characterized in that the active substance (D) has a solubility in water of less than 10 g/l at 25⁰C and 1 atm (1013 mbar).

13. The process according to any one of claims 1 1 to12, characterized in that the active sub- stance (D) is a pesticide.

14. The process according to any one of claims 11 to 13, characterized in that the solvent is selected from the group consisting of esters of lower aliphatic carboxylic acid with lower a- liphatic alcohol, preferably ethyl acetate and butyl acetate.

15. A ready-for-use formulation comprising the formulation as defined in any one of claims 1 to 10.

16. A process for the preparation of a ready-for-use formulation, including the step of mixing the formulation as defined in any of claims 1 to 10 with water.