USOO821 1469B2

(12) United States Patent (10) Patent No.: US 8,211,469 B2 Dieckmann et al. (45) Date of Patent: Jul. 3, 2012

(54) USE OF BLOCK COPOLYMERS BASED ON 6,767,865 B2 * 7/2004 Den Tandt et al...... 504,362 VNYLLACTAMS AND VINYLACETATE AS 6,867,262 B1 3/2005 Angel et al. SOLUBLIZERS 2002fOO37318 A1 3/2002 Meffert et al. 2007/O122436 A1 5/2007 Koltzenburg et al. (75) Inventors: Yvonne Dieckmann, Hafloch (DE); FOREIGN PATENT DOCUMENTS Murat Mertoglu, Ludwigshafen (DE); DE 1245542 7, 1967 Rainer Dobrawa, Mannheim (DE); DE 19935063 2, 2001 Szilard Csihony, Weinheim (DE): EP O781550 7/1997 Cedric Dieleman, Scheibenhard (FR); EP 991683 12/1997 Torsten Knieriem, Mannheim (DE); EP O876819 11, 1998 Sebastian Koltzenburg, EP 948957 10, 1999 Dannstadt-Schauernheim (DE); Holger EP O953347 11, 1999 EP 1027886 8, 2000 Tirk, Mannheim (DE); Ulrike EP 126.9994 1, 2003 Troppmann, Mannheim (DE); EP 1510 533 3, 2005 Christian Michael Jung, Ludwigshafen WO WO98/O1478 1, 1998 (DE) WO WOOO53164 9, 2000 WO WO 2004O19901 3, 2004 (73) Assignee: BASFSE, Ludwigshafen (DE) WO WO 2004035O13 4/2004 WO WO 2005/046328 5, 2005 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 OTHER PUBLICATIONS U.S.C. 154(b) by 299 days. International Search Report for International Application No. PCT/ (21) Appl. No.: 12/514,078 EP2007/061759: International Filing Date: Oct. 31, 2007; Date of Completion: Feb. 25, 2008; Date of Mailing: Mar. 6, 2008. (22) PCT Filed: Oct. 31, 2007 International Preliminary Report on Patentability for International Application No. PCT/EP2007/061759: International Filing Date: (86). PCT No.: PCT/EP2007/061759 Oct. 31, 2007. S371 (c)(1), Bilalis et al., “Controlled nitroxide-mediated and reversible addition (2), (4) Date: May 8, 2009 fragmentation chain transfer polymerization of n-vinylpyrrollidone: Synthesis of block copolymers with styrene and 2-vinylpyridine'. (87) PCT Pub. No.: WO2008/058848 Journal of Polymer Science: Part A, 44, 659-665 (2006). Nguyen, T.L. Uyen et al., “Investigation of the influence of the PCT Pub. Date: May 22, 2008 architectures of poly(vinyl pyrrollidone) polymers made via the reversible addition-fragmentation chain transfer/macromolecular (65) Prior Publication Data design via the interchange of Xanthates mechanism on the stabiliza US 201O/OO472O3 A1 Feb. 25, 2010 tion of Suspension polymerizations'. Journal of Polymer Science: Part A, 44, 4372-4383 (2006). (30) Foreign Application Priority Data Römpp Chemie Lexikon, 9. Auflage, Bd. 5, S. 4203. Thieme Verlag, Stuttgart, 1992. Nov. 13, 2006 (EP) ...... O6123959 Dec. 5, 2006 (EP) ...... O6125423 * cited by examiner (51) Int. Cl. A6 IK 9/14 (2006.01) Primary Examiner — Paul Dickinson (52) U.S. Cl...... 424/486 (74) Attorney, Agent, or Firm — Brinks Hofer Gilson & (58) Field of Classification Search ...... None Lione See application file for complete search history. (56) References Cited (57) ABSTRACT Use of polyvinylactam-polyvinyl acetate block copolymers U.S. PATENT DOCUMENTS as solubilizers for active ingredients that are sparingly soluble 5,502,136 A 3/1996 Zhong et al. in water. 5,900,247 A 5, 1999 Rault et al. 6,075,107 A 6, 2000 Kothrade et al. 6,153,705 A 11/2000 Corpart et al. 6,271,307 B1 8, 2001 Huffet al. 14 Claims, No Drawings US 8,211,469 B2 1. 2 USE OF BLOCK COPOLYMERS BASED ON EP-A953 347 discloses the use of graft polymers contain VNYLLACTAMS AND VNYLACETATE AS ing polyalkylene oxide as solubilizers. The graft polymers of SOLUBLIZERS vinyl acetate and polyalkylene oxides described therein often do not constitute powders, but viscous-Sticky liquids, which This application is a National Stage application of Interna is disadvantageous from the point of view of application. tional Application No. PCT/EP2007/061759 filed Oct. 31, EP 0781 550 discloses the use of random copolymers of 2007, the entire contents of which is hereby incorporated vinylpyrrolidone and vinyl acetate as bioadhesion agents in herein by reference. This application also claims the benefit pharmacy. under 35 U.S.C. S 119 of European Patent Application No. DE 1245542 discloses the use of random copolymers of 10 polyvinylpyrrolidone with vinyl acetate as solvent for peptide 06123959.6, filed Nov. 13, 2006 and European Patent Appli antibiotics. The block copolymer specified is the block cation No. 06125423.1, filed Dec. 5, 2006, the entire contents copolymer of polyoxyethylene and polyoxypropylene. of which is hereby incorporated herein by reference. Numerous types of block polymers are prepared by ionic The present invention relates to the use of block copoly polymerization. However, this method is not suitable for all mers based on vinyllactams and vinyl acetate as Solubilizers 15 monomers. A polymerization via free-radically initiated and crystallization inhibitors for active ingredients that are methods is open to a large number of monomers, but a normal sparingly soluble in water, in particular of pesticides (agro free-radical polymerization cannot be used for producing chemical active ingredients). block copolymers. In the production of homogenous preparations in particular For this reason, the method of controlled free-radical poly of biologically active substances, the solubilization of hydro merization, which is also referred to as “living polymeriza phobic Substances, i.e. Substances that are sparingly soluble tion, was developed. in water, has gained very great practical importance. One variant of living free-radical polymerization is the Solubilization is to be understood as meaning making Sub so-called “RAFT method (RAFT: Reversible Addition stances that are insoluble or sparingly soluble in a certain Fragmentation chain Transfer). Here, suitable chain transfer Solvent, in particular water, soluble through interface-active 25 agents, which are also referred to as RAFT reagents, are compounds, the solubilizers. Such solubilizers are able to certain Sulfur compounds, for example dithiocarbamates or convert sparingly water-soluble or water-insoluble sub Xanthates. stances into clear, at most opalescent, aqueous solutions with EP-B 991 683 describes the production of block copoly out the chemical structure of these Substances undergoing a mers from polyvinyl acetate and polyalkyl acrylate blocks via change as a result (cf. Römpp Chemie Lexikon, 9th edition, 30 living polymerization with Xanthates. vol. 5, p. 4203. Thieme Verlag, Stuttgart, 1992). WO98/01478 discloses the production of block polymers The solubilisates produced are characterized in that the of polyalkyl acrylates and polystyrenes via living polymer sparingly water-soluble or water-insoluble Substance is ization with thiocarbonylthio compounds as chain transfer present in colloidally dissolved form in the molecular asso agents. ciations of the Surface-active compounds which form in aque 35 EP-A 1510533 describes the production of block copoly ous solution, such as, for example, hydrophobic domains or mers comprising polyvinyllactam blocks by living polymer micelles. The resulting solutions are stable or metastable ization. The polyvinylactam block here may also be a single-phase systems which appear optically clear to opales copolymer of vinylactam and up to 45% by weight of vinyl Cent. acetate. The coblocks described are polyhydrocarbons or Solubilizers can, for example, improve the appearance of 40 poly(meth)acrylates. cosmetic formulations and of food preparations by making P. Bilalis et al., Journal of Polymer Science: Part A. Vol. 44. the formulations transparent. Furthermore, in the case of 659-665 (2006) discloses the production of polyvinylpyrroli pharmaceutical preparations, the bioavailability and thus the done block copolymers by means of RAFT polymerization. effect of drugs can also be increased through the use of T. L. Uyen Nguyen et al. describe in Journal of Polymer solubilizers. 45 Science: Part A. Vol. 44, 4372-4383 (2006) the production of The Solubilizers used for pharmaceutical drugs and cos block copolymers of polyvinylpyrrolidone and polyvinyl metic active ingredients are preliminary Surfactants such as acetate blocks by controlled polymerization, and the use of ethoxylated ricinus oil or ethoxylated hydrogenated ricinus Such block copolymers as stabilizers in the Suspension poly oil, ethoxylated sorbitan fatty acid esters or ethoxylated merization of special crosslinked polymer microspheres. hydroxy Stearic acid. 50 A further desirable requirement of solubilizers is the ability The above-described solubilizers used hitherto, however, to form so-called “solid solutions' with sparingly soluble have a number of application-related disadvantages. substances. The term "solid solution” refers to a state in which The known solubilizers have only a slight solubilizing a Substance is distributed in microdisperse form or, in the effect for some sparingly soluble drugs, such as, for example, ideal case, in molecularly disperse form, in a solid matrix, for clotrimazole. 55 example a polymer matrix. Such solid solutions lead, for EP-A 876 819 describes the use of copolymers of at least example when used in Solid pharmaceutical administration 60% by weight of N-vinyl-pyrrolidone and amides or esters forms of a sparingly soluble active ingredient, to improved with long-chain alkyl groups. release of the active ingredient. An important requirement of EP-A 948957 describes the use of copolymers of mono Such solid solutions is that they are also stable upon storage ethylenically unsaturated carboxylic acids, such as, for 60 over an extended period, i.e. that the active ingredient does example, acrylic acid, and hydrophobically modified not crystallize out. Furthermore, the capacity of the solid comonomers, such as, for example, N-alkyl- or N,N-dialky solution, in other words the ability to form stable solid solu lamides of unsaturated carboxylic acids with Cs-Co-alkyl tions with the highest possible active ingredient contents, is radicals. also of importance. DE-A 199 350 63 discloses graft polymers containing 65 Solid solution here refers to a state in which the active polyalkylene oxide on the basis of vinyllactams and vinyl ingredient is present in molecularly disperse distribution in a acetate, and their use as gas hydrate inhibitors. matrix of auxiliaries. In this state, crystalline fractions of the US 8,211,469 B2 3 4 active ingredient can no longer be established by means of mers according to the invention can simultaneously solve the X-ray diffractometry. Since the detection limit for crystalline abovementioned problems of solubilization and of crystalli fractions in X-ray diffractometry is 3% by weight, the expres zation inhibition. sion “no crystalline fractions’ means that less than 3% by For the purposes of the present invention, active ingredi weight of crystalline fractions are present. The state of the ents are understood as meaning biologically active substances molecularly disperse distribution can be ascertained with the which are used in pharmaceutical preparations or cosmetic help of the differential scanning calorimetry (DSC) method. preparations, food Supplements or foods. They are also under In the case of a molecularly disperse distribution, a melting stood as meaning biologically active Substances for agro peak can no longer be observed in the region of the melting chemical applications (also called pesticides or agrochemical point of the active ingredient. The detection limit of this 10 active ingredients). method is 1% by weight. WO 05/046328 gives examples of In particular, these block copolymers are Suitable as solu Solid solutions. bilizers and/or crystallization inhibitors for pesticides that are For the formation of solid solutions, besides the fundamen sparingly soluble in water. tal ability of the solubilizers to form solid solutions, the 15 The block copolymers may be of the AB, ABA or BAB hygroscopicity of the solubilizers also plays an important type. role. Solubilizers which absorb too much water from the Suitable as polyvinylactam are N-vinylpyrrolidone, N-vi ambient air lead to deliquescence of the solid solution and the nylpiperidone or N-vinylcaprolactam, preferably polyvi undesired crystallization of the active ingredients. An exten nylpyrrolidone. sively great hygroscopicity can also present problems during The molar ratio of polyvinylactam to polyvinyl acetate processing to give administration forms or Solid agrochemi (PVAc) can be 10 to 90 to 90 to 10, preferably 30 to 70 to 70 cal preparations. to 30, particularly preferably 60:40 to 40:60. Particularly in the case of agrochemical preparations, this Hereinafter, the polyvinylactam block is also referred to as can lead to problems during storage as a result of so-called A block, and the polyvinyl acetate block is referred to as B agglutination. 25 block. The hitherto known polymeric solubilizers have the disad In principle, the block copolymers can be prepared by any vantages that they do not form stable solid solutions. Further method suitable for this purpose. more, they still leave room for improvements regarding Solu Thus, for example, coupling of the PVP and the PVAc bilization in aqueous systems. Some of the known blocks can take place via diisocyanates. solubilizers also have disadvantages with regard to process 30 In order to make it possible for the polyvinyl acetate block ability on account of their tendency toward stickiness since to couple onto the polyvinylactam block, the polymer blocks they do not constitute adequately flowable powders. are functionalized at the chain start and/or at the chain end Furthermore, particularly in the case of agrochemical with hydroxyl groups. The OH functionalization can be preparations, it is of importance to achieve high storage sta 35 achieved either via the radical starter or via a regulator. Func bility of the preparation through selection of suitable solubi tionalization via the radical starter takes place at the chain lizers (e.g. by avoiding crystallization formation) and/or, start, functionalization via the regulator at the chain end. In through selection of a suitable solubilizer, to increase the order to achieve a functionalization, at least one radical starter bioavailability of the pesticide and/or have the lowest pos carrying hydroxyl groups or one regulator carrying hydroxyl sible phytotoxicity. There is a constant need here to find 40 groups must therefore be used in the polymerization of the suitable solubilizers. prepolymers. If B-A-B or A-B-A block copolymers are to be In the case of the formulation of active ingredients that are produced, radical starters and regulators must carry hydroxyl sparingly soluble in water, there is the problem that the spar groups. ingly soluble active ingredient in the aqueous formulation has General methods of producing the vinyllactam prepoly a tendency toward crystallization during storage. For spar 45 mers and the polyvinyl acetate prepolymers are known perse. ingly soluble active ingredients, this problem is naturally The production takes place by free-radically initiated poly closely related to the problem of lack of solubilization. merization in Suitable solvents. It was therefore the object to provide novel and improved Suitable N-vinyllactams are N-vinylpyrrolidone, N-vinyl solubilizers for pharmaceutical, cosmetic, food or agro caprolactam or N-vinylpiperidone or mixtures thereof. Pref chemical applications which do not have the described dis 50 erence is given to using N-vinylpyrrolidone. advantages. Moreover, it is an object of the present invention Suitable nonaqueous solvents are, for example, alcohols, to provide solubilizers in particular for sparingly soluble pes Such as methanol, ethanol, n-propanol, and isopropanol, and ticides which permit high storage stability of the agrochemi also glycols, such as ethylene glycol and glycerol. cal preparations and/or increase the bioavailability of the Also suitable as solvents are acetic acid esters, such as, for pesticide and/or have the lowest possible phytotoxicity. 55 example, ethyl acetate or butyl acetate. As already explained, it was an object of the present inven Preference is given to using those solvents which do notact tion to provide improved copolymers as Solubilizers and as as regulator. These are known to the person skilled in the art. crystallization inhibitors. For the solvents for producing the polyvinyl acetate, that Accordingly, the use of block copolymers consisting of at stated above is applicable. least one polyvinylactam block and at least one polyvinyl 60 The polymerization is preferably carried out at tempera acetate block as solubilizers for active ingredients that are tures from 60 to 100° C. sparingly soluble in water has been found. Furthermore, To initiate the polymerization, free-radical initiators are accordingly, the use of block copolymers consisting of at least used as radical starters. The amounts of initiator or initiator one polyvinyllactam block and at least one polyvinyl acetate mixtures used, based on monomerused, are between 0.01 and block as crystallization inhibitors for active ingredients that 65 10% by weight, preferably between 0.3 and 5% by weight. are sparingly soluble in water, preferably pesticides, has been Depending on the type of solvent used, both organic and found. Furthermore, it has been found that the block copoly inorganic peroxides are suitable. Such as Sodium persulfate or US 8,211,469 B2 5 6 aZo starters such as azobisisobutyronitrile, azobis(2-ami Irrespective of which embodiment is selected, the reaction dopropane) dihydrochloride or 2,2'-azobis(2-methylbuty can take place as follows: ronitrile). Suitable diisocyanates are compounds of the general for Peroxidic initiators are, for example, dibenzoyl peroxide, mula OCN R NCO, where R may be aliphatic, alicyclic diacetyl peroxide, succinyl peroxide, tert-butyl perpivalate, 5 or aromatic radicals, which can also be substituted by alkyl tert-butyl 2-ethylhexanoate, tert-butyl permaleinate, bis(tert radicals. butylperoxy)cyclohexane, tert-butyl peroxyisopropylcarbon Suitable diisocyanates are preferably compounds whose ate, tert-butyl peracetate, 2.2-bis(tert-butylperoxy)butane, isocyanate groups have varying reactivity, on account of the dicumyl peroxide, di-tert-amyl peroxide, di-tert-butyl peroX molecular structure, toward nucleophiles, for example iso 10 phorone diisocyanate or toluoylene diisocyanate. ide, p-menthane hydroperoxide, pinane hydroperoxide, Also Suitable in principle are symmetrical diisocyanates, cumene hydroperoxide, tert-butyl hydroperoxide, hydrogen Such as, for example, hexamethylene diisocyanate or 4,4'- peroxide, and mixtures of the specified initiators. The speci methylenedi(phenyl isocyanate). fied initiators can also be used in combination with redox Preference is given to using isophorone diisocyanate. components such as ascorbic acid. 15 The reaction with the diisocyanate preferably takes place in If the OH functionalization is to take place via the radical an organic solvent. Such as ketones, for example acetone, starter, OH-functionalized starters in particular are suitable, furthermore dimethylsulfoxide, dimethylformamide, or gen such as, for example, 2,2'-azobis 2-methyl-N-(2-hydroxy erally aprotic-polar organic solvents or mixtures of Such sol ethyl)propionamide. 2,2'-azobis-(2-methyl-N-2-(1-hy vents. The reaction usually takes place at elevated tempera droxybutyl)propionamide or 2,2'-azobis(2-1-(2-hydroxy- 20 tures, the temperature also being governed by the boiling ethyl)-2-imidazolin-2-yl)propane} dihydrochloride. temperature of the selected solvent. The reaction of the diiso The free-radical polymerization can, if appropriate, take cyanate with the first component can take place at 20 to 50° place in the presence of emulsifiers, if appropriate further C., but also if desired up to 100°C. The reaction of the second protective colloids, if appropriate buffer systems and if appro isocyanate group can take place at temperatures from 50 to priate Subsequent pH adjustment by means of bases or acids. 25 1000 C. Suitable molecular weight regulators are hydrogen Sulfide The reaction preferably takes place in equimolar amounts, compounds, such as alkyl mercaptains, e.g. n-dodecylmercap which means that the quantitative ratio is selected Such that, tan, tert-dodecyl mercaptan, thioglycolic acid and esters per mole of hydroxyl group to be reacted, 1 mol of diisocy thereof, mercaptoalkanols such as mercaptoethanol. Further anate is used. If the vinyllactam polymer is OH-functional suitable regulators are specified, for example, in DE 197 12 30 ized via a regulator, the diisocyanate is reacted in equimolar 247 A1, page 4. The required amount of molecular weight amounts relative to the regulator. If the vinyllactam polymer regulator is in the range from 0 to 5% by weight, based on the is OH-functionalized via a radical starter, then 2 mol of diiso amount of monomers to be polymerized, in particular 0.05 to cyanate are used per mole of radical starter. 2% by weight, particularly preferably 0.1 to 1.5% by weight. In the case of symmetrical diisocyanates, it may also be Preference is given to mercaptoethanol. 35 advisable to use an excess of diisocyanate and then to remove The monomers or a monomer mixture or the monomer(s) the excess by distillation. emulsion are initially introduced together with the initiator, The reaction is preferably carried out in the presence of a which is usually in the form of a solution, in a stirred reactor catalyst. Suitable catalysts are, for example, organometallic at the polymerization temperature (batch process), or metered compounds such as organotitanium compounds or Zinc com into the polymerization reactor if appropriate continuously or 40 pounds, such as dibutyltin dilaurate or tin octoate, further in a plurality of successive stages (feed method). In the case of more bases Such as 1,4-diaza (2.2.2)bicyclooctane or tetram the feed method, it is customary, before the start of the actual ethylbutanediamine. The catalyst can be used in amounts of polymerization, for the reactor to already contain, besides from 0.05 to 0.2 mol, preferably 0.1 to 0.14 mol, per mole of water (in order to permit stirring of the reactor) part amounts, diisocyanate. rarely the total amount intended for the polymerization, of the 45 The reaction is usually carried out at elevated temperatures feed materials such as emulsifiers, protective colloids, mono in the range from 50 to 100° C. Which temperature is selected mers, regulators etc. or part amounts of the feeds (including specifically depends on the nature of the organic solvent used. monomer feed or emulsion feed and initiator feed). The solvent can then be removed by distillation. The polyvinyl acetates are reacted in equimolar amounts, Usually, the reaction is carried out in such away that firstly based on the hydroxyl groups in the polyvinyl acetate and in 50 the component, which should be isocyanate-group-function the vinylactam prepolymer. The amount of OH groups alized, is reacted with the diisocyanate in the presence of the present can, if required, be ascertained in a manner known per catalystanda solvent until the isocyanate value in the reaction se to the person skilled in the art. To ascertain the hydroxyl mixture has dropped to half. This can be ascertained in a number, see, for example, Römpp Chemie Lexikon, 9th edi known manner, for example titrimetrically. The other com tion, 1990. 55 ponent is then added, the amounts of isocyanate groups and The coupling of vinylactam polymers and polyvinyl OH or amino groups again being selected to be equimolar. acetates takes place through reaction with diisocyanates, the The reaction is continued until the isocyanate value has reaction with the hydroxyl groups of the polymer resulting in dropped to Zero. coupling via urethane groups. In this connection, either the The block copolymers are preferably prepared by a vinylactam polymer or the polyvinyl acetate can firstly be 60 method, known perse, of controlled free-radical polymeriza reacted with the diisocyanate. tion, which is also referred to as RAFT polymerization (Re According to a preferred embodiment of the invention, the versible Addition Fragmentation chain Transfer). The coupling takes place via polyvinyl acetates functionalized mechanism of this method is described in detail in WO with isocyanate groups as end groups. For this, the polyvinyl 98/01478 and EP-A 991 683, to the disclosure of which acetate is firstly reacted with the diisocyanate and then the 65 reference is hereby expressly made. polyvinyl acetate functionalized in this way is reacted with The RAFT polymerization takes place in the presence of the vinylactam polymer. specific chain transfer agents, also referred to as RAFT US 8,211,469 B2 7 8 reagents, from the group of thiocarbonylthio compounds, in means, for example, that at least 30 g, but in many cases also particular the dithiobenzoates, the trithiocarbonates, the at least 100 g, of water is required per g of Substance. In the dithiocarbamates and the dithiocarbonic acid esters, which case of virtually insoluble substances, at least 10 000 g of are also referred to as Xanthates. Such reagents are known to water are required per g of Substance. the person skilled in the art from the prior art. Thus, of 5 For the purposes of the present invention, pharmaceutical suitability are, for example, the compounds described in WO active ingredients that are sparingly soluble in water are to be 98/O1478 or EP-A991 683. understood as meaning those active ingredients which are Preferred RAFT reagents are diphenyl dithiocarbamate of used for producing drugs for humans and animals, for cos diethyl malonate and 2-(ethoxycarbonothioyl)thiopropionic metic preparations or as food Supplements such as Vitamins or acid. 10 provitamins or dietetic active ingredients. To produce the block copolymer, the PVP block is firstly Also Suitable as sparingly soluble active ingredients to be prepared by free-radically initiated solution polymerization solubilized are dyes for use in compositions for human or by mixingN-vinyllactam, RAFT reagent and radical starter in animal nutrition. a solvent and reacting them at elevated temperature. Likewise under consideration according to the invention Suitable radical starters are azo starters, such as 2,2'-aZobis 15 are agrochemical active ingredients for treatment against (2,4-dimethylvaleronitrile), dimethyl, azobisisobutyronitrile, harmful organisms, such as, for example, insecticides, herbi dimethyl 2,2'-azobisisobutyrate, 1,1'-azobis(1-cyclo-hexan cides or fungicides, and plant growth Substances or agents for ecarbonitrile), 2,2'-azobis(2-methylbutyronitrile) or 4,4'-azo seed treatment. bis(2-methyl-N-(2-hydroxyethyl)propionamide, preferably Through the present invention are provided, in particular, azobisisobutyronitrile (AIBN). The radical starter can be amphiphilic compounds for use as solubility promoters for used in amounts of from 5 to 50 mol%, preferably 5 to 15 mol pharmaceutical and cosmetic preparations and also for food %, based on RAFT reagent. preparations. They have the property of solubilizing sparingly The vinyllactam monomers, RAFT reagents and radical soluble active ingredients in the field of pharmacy and cos starters can be used in molar ratios of from 350:2:1 (mono metics, sparingly soluble food Supplements, for example vita mer:RAFT:starter) to 3500:10:1, preferably 1000:10:1 to 25 mins and carotenoids, but also sparingly soluble active ingre 2000:10:1. dients for use in crop protection compositions (also called Suitable solvents are organic solvents which do not act as pesticides or agrochemical active ingredients), and also vet regulators, for example methanol, n-propanol, tert-butanol, erinary medicine active ingredients. dimethylformamide, ethyl acetate, butyl acetate or dioxane, Further provided by the present invention are, in particular, preferably dioxane or tert-butanol. 30 amphiphilic compounds for use as crystallization inhibitor The reaction can take place at temperatures of from 50 to for pharmaceutical, cosmetic or agrochemical preparations, 120° C., preferably 60 to 80° C. and for food preparations. Preferably, amphiphilic com When the polymerization is complete, it is advisable to pounds for use as crystallization inhibitor for agrochemical treat the polyvinylactam functionalized with RAFT reagent preparations are provided. They have the property of inhibit in Such away that any unreacted vinylactam is removed. This 35 ing the crystallization of sparingly soluble active ingredients can take place, for example, by precipitating the polymer out in the field of pharmacy and cosmetics, sparingly soluble food of the reaction mixture and removing it by filtration. The Supplements, for example vitamins and carotenoids, but also precipitation can take place, for example, by adding a non sparingly soluble active ingredients for use in crop protection solvent. A suitable nonsolvent is primarily diethyl ether. Fur compositions (also called pesticides or agrochemical active thermore, the polymer can also be purified by acidic hydroly 40 ingredients), and also veterinary medicine active ingredients sis of the monomeric vinylactam with Subsequent removal of Solubilizers for Cosmetics: the resulting lactam by distillation. According to the invention, the copolymers can be used as The PVP block functionalized with the RAFT reagent is solubilizers in cosmetic formulations. For example, they are then reacted with vinyl acetate in the presence of a radical suitable as solubilizers for cosmetic oils. They have good Starter. 45 solubilization ability for fats and oils, such as peanut oil, Suitable radical starters are the compounds described for jojoba oil, coconut oil, almond oil, olive oil, palm oil, ricinus the production of the polyvinylactam block. The reaction can oil, Soy oil or wheatgerm oil, or for essential oils, such as otherwise take place under the conditions described for the dwarf-pine oil, lavender oil, rosemary oil, fir needle oil, pine formation of the polyvinyllactam block. needle oil, eucalyptus oil, peppermint oil, sage oil, bergamot When the polymerization is complete, the resulting block 50 oil, turpentine oil, Melissa oil.juniper oil, lemon oil, anise oil, polymer can be worked-up in a manner customary perse, for cardamom oil, peppermint oil, camphor oil, etc. or for mix example by separating off the solvent by distillation. tures of these oils. The block copolymers are preferably water-soluble, but Furthermore, the polymers according to the invention can may also be water-dispersible. be used as solubilizers for UV absorbers that are insoluble or The molecular weights Mn may be 5000 to 50 000, pref 55 sparingly soluble in water, such as, for example, 2-hydroxy erably 10 000 to 30 000. 4-methoxybenzophenone (Uvinul RM 40, BASF), 2.2',4,4'- Applications: tetrahydroxy-benzophenone (Uvinul R. D. 50), 2,2'-dihy The copolymers to be used according to the invention can droxy-4,4'-dimethoxybenzophenone (Uvinul RD49), 2,4- in principle be used in all fields where active ingredients that dihydroxybenzophenone (Uvinul R. 400), 2-ethylhexyl are insoluble or only sparingly soluble in water are to be used 60 2-cyano-3,3-diphenylacrylate (Uvinul R N 539), 2,4,6-tri for certain applications on people and animals or in the agro anilino-p-(carbo-2'-ethylhexyl-1'-oxy)-1,3,5-triazine chemical sector either in aqueous preparations, or their effect (Uvinul RT 150), 3-(4-methoxybenzylidene)camphor (Euso is to develop in an aqueous medium. lex(R) 6300, Merck), 2-ethylhexyl N,N-dimethyl-4-ami According to the invention, the term "sparingly soluble in nobenzoate (Eusolex(R) 6007), 3,3,5-trimethyl-cyclohexyl water also comprises virtually insoluble substances and 65 salicylate, 4-isopropyldibenzoylmethane (Eusolex(R) 8020), means that for a solution of the substance in water at 20°C., 2-ethylhexyl p-methoxycinnamate and 2-isoamyl p-meth at least 30 to 100g of waterpergofsubstance is required. This oxycinnamate, and mixtures thereof. US 8,211,469 B2 10 The present invention therefore also provides cosmetic Pharmaceutical formulations of the type specified above preparations which comprise at least one of the copolymers can be obtained by processing the claimed copolymers with according to the invention of the composition specified at the pharmaceutical active ingredients by conventional methods start as solubilizers. Preference is given to those preparations and using known and new active ingredients. which, besides the solubilizer, comprise one or more spar The use according to the invention can additionally com ingly soluble cosmetic active ingredients, for example the prise pharmaceutical auxiliaries and/or diluents. CoSolvents, abovementioned oils or UV absorbers. stabilizers, preservatives in particular are listed as auxiliaries. These formulations are solubilisates based on water or The pharmaceutical active ingredients used are substances waterfalcohol. The solubilizers according to the invention are that are slightly soluble or insoluble in water. According to used in the ratio from 0.2:1 to 20:1, preferably 1:1 to 15:1, 10 DAB 9 (German pharmacopoeia), the grading of the solubil particularly preferably 2:1 to 12:1, relative to the sparingly ity of pharmaceutical active ingredients is as follows: slightly soluble cosmetic active ingredient. soluble (soluble in from 30 to 100 parts of solvent); sparingly The content of solubilizer according to the invention in the soluble (soluble in from 100 to 1000 parts of solvent); virtu cosmetic preparation is, depending on the active ingredient, ally insoluble (soluble in more than 10 000 parts of solvent). in the range from 1 to 50% by weight, preferably 3 to 40% by 15 The active ingredients here may be from any indication field. weight, particularly preferably 5 to 30% by weight. Examples which may be specified here are benzodiaz In addition, further auxiliaries can be added to this formu epines, antihypertensives, vitamins, cytostatics—in particu lation, for example nonionic, cationic or anionic Surfactants, lar taxol, anesthetics, neuroleptics, antidepressants, antiviral Such as alkyl polyglycosides, fatty alcohol Sulfates, fatty alco agents, such as, for example, anti-HIV agents, antibiotics, hol ether sulfates, alkanesulfonates, fatty alcohol ethoxylates, antimycotics, antidementia drugs, fungicides, chemothera fatty alcohol phosphates, alkylbetaines, sorbitan esters, POE peutics, urologics, platelet aggregation inhibitors, Sulfona Sorbitan esters, Sugar fatty acid esters, fatty acid polyglycerol mides, spasmolytics, hormones, immunoglobulins, Sera, thy esters, fatty acid partial glycerides, fatty acid carboxylates, roid therapeutic agents, psychopharmacological agents, fatty alcohol SulfoSuccinates, fatty acid sarcosinates, fatty agents for treating Parkinson's disease and other antihyper acid isethionates, fatty acid taurates, citric acid esters, sili 25 kinetic agents, ophthalmics, neuropathy preparations, cal cone copolymers, fatty acid polyglycol esters, fatty acid cium metabolism regulators, muscle relaxants, anesthetics, amides, fatty acid alkanolamides, quaternary ammonium lipid-lowering agents, hepatic therapeutic agents, coronary compounds, alkylphenol oxethylates, fatty amine oxethy agents, cardiacs, immunotherapeutics, regulatory peptides lates, cosolvents such as ethylene glycol, propylene glycol, and their inhibitors, hypnotics, sedatives, gynecological glycerol etc. 30 agents, gout remedies, fibrinolytic agents, enzyme prepara Other constituents which can be added are natural or syn tions and transport proteins, enzyme inhibitors, emetics, cir thetic compounds, e.g. lanolin derivatives, cholesterol deriva culation-promoting agents, diuretics, diagnostics, corticoids, tives, isopropyl myristate, isopropyl palmitate, electrolytes, cholinegenics, bile duct therapeutics, antiasthmatics, bron dyes, preservatives, acids (e.g. lactic acid, citric acid). cholytics, beta receptor blockers, calcium antagonists, ACE These formulations are used, for example, in bath additive 35 inhibitors, arteriosclerotics, antiphlogistics, anticoagulants, preparations such as bath oils, aftershaves, face toners, hair antihypotonics, antihypoglycemics, antihypertensives, anti tonics, eau de cologne, eau de toilette, and in Sunscreen com fibrinolytics, antiepileptics, antiemetics, antidotes, antidia positions. A further field of use is the oral care sector, for betics, antiarrhythmics, antianemics, antiallergics, anthelm example in mouthwashes, toothpastes, adhesive creams for intics, analgesics, analeptics, aldosterone antagonists, dentures and the like. 40 Slimming agents. Description of the Solubilization Method: One possible production variant is the dissolution of the In the production of the solubilisates for cosmetic formu solubilizer in the aqueous phase, if appropriate with gentle lations, the copolymers according to the invention can be used heating, and the Subsequent dissolution of the active ingredi as 100% strength substance or preferably as aqueous solution. ent in the aqueous solubilizer Solution. The simultaneous Usually, the solubilizer is dissolved in water and inten 45 dissolution of solubilizer and active ingredient in the aqueous sively mixed with the sparingly soluble cosmetic active ingre phase is likewise possible. dient to be used in each case. The copolymers according to the invention can also be However, it is also possible to intensively mix the solubi used as solubilizers in a manner which, for example, involves lizer with the sparingly soluble cosmetic active ingredient to dispersing the active ingredient in the solubilizer, if appropri be used in each case and then to add demineralized water with 50 ate with heating, and mixing it with water with stirring. continuous stirring. Furthermore, the solubilizers can also be processed in the Solubilizers for Pharmaceutical Applications: melt with the active ingredients. In particular, Solid solutions The claimed copolymers are likewise suitable for use as can be obtained in this way. Ofsuitability for this is, interalia, solubilizer in pharmaceutical preparations of all types which also the method of melt extrusion. A further way of producing are characterized in that they can comprise one or more drugs 55 Solid solutions is also to prepare solutions of Solubilizer and that are insoluble or sparingly soluble in water, as well as active ingredient in Suitable organic solvents and then to Vitamins and/or carotenoids. These are in particular aqueous remove the solvent by customary methods. Solutions or solubilisates for oral application. The invention therefore also generally provides pharma Thus, the claimed copolymers are suitable for use in oral ceutical preparations which comprise at least one of the administration forms, such as tablets, capsules, powders, 60 copolymers according to the invention as solubilizer. Prefer Solutions. Here, they can provide the sparingly soluble drug ence is given to those preparations which, besides the solu with increased bioavailability. In particular, solid solutions of bilizer, comprise pharmaceutical active ingredient that is active ingredient and Solubilizer are used. insoluble or sparingly soluble in water, for example from the In the case of parenteral application, besides solubilizates, abovementioned indication fields. it is also possible to use emulsions, for example fatty emul 65 Of the abovementioned pharmaceutical preparations, par sions. For this purpose too, the claimed copolymers are Suit ticular preference is given to those which are orally applicable able for processing a sparingly soluble drug. formulations. US 8,211,469 B2 11 12 The content of solubilizer according to the invention in the A.3. pyrethroids: allethrin, bifenthrin, cyfluthrin, cyhalo pharmaceutical preparation is, depending on the active ingre thrin, cyphenothrin, cypermethrin, alpha-cypermethrin, beta dient, in the range from 1 to 75% by weight, preferably 5 to cypermethrin, Zeta-cypermethrin, deltamethrin, esfenvaler 60% by weight, particularly preferably 5 to 50% by weight. ate, etofenproX, fempropathrin, fenvalerate, imiprothrin, A further particularly preferred embodiment relates to 5 lambda-cyhalothrin, permethrin, prallethrin, pyrethrin I and pharmaceutical preparations in which the active ingredients II, resmethrin, silafluofen, tau-fluvalinate, tefluthrin, tet and the solubilizer are present as solid solution. Here, the ramethrin, tralomethrin, transfluthrin; weight ratio of solubilizer to active ingredient is preferably from 1:1 to 4:1, but can be up to 100:1, in particular up to 15:1. A.4. growth regulators: a) chitin synthesis inhibitors: ben What matters is only that, when used in the finished drug 10 Zoylureas: chlorfluaZuron, cyramazin, diflubenZuron, flucy form, firstly an effective amount of active ingredient is com cloXuron, flufenoXuron, hexaflumuron, lufenuron, novalu prised in the drug form, and secondly in the case of oral drug ron, teflubenzuron, triflumuron; buprofezin, diofenolan, forms, the forms do not become too large. hexythiaZOX, etoxazole, clofentazine; b) ecdysone antago Solubilizers for Food Preparations: nists: halofenozide, methoxyfenozide, tebufenozide, aza Besides use in cosmetics and pharmacy, the copolymers 15 dirachtin; c) juvenoids: pyriproxyfen, methoprene, fenoxy according to the invention are also suitable as solubilizers in carb; d) lipid biosynthesis inhibitors: spirodiclofen, the food sector for sparingly water-soluble or water-insoluble spiromesi?en, a tetronic acid derivative of formula T', nutrients, auxiliaries or additives, such as, for example, fat soluble vitamins or carotenoids. Examples which may be mentioned are beverages colored with carotenoids. 2O (Tl) Solubilizers for Agrochemical Active Ingredients (Pesti cides): In a preferred embodiment of the present invention, the copolymers can be used as solubilizers in agrochemical preparations. 25 The present invention therefore also provides agrochemi cal preparations which comprise at least one of the copoly mers according to the invention as Solubilizers and at least one sparingly soluble pesticide. In a further preferred embodiment of the present invention, 30 the copolymers can be used as crystallization inhibitors in A.5. nicotin receptor agonists/antagonists: clothianidin, agrochemical preparations. dinotefuran, thiacloprid; The present invention therefore also provides agrochemi cal preparations which comprise at least one of the copoly A.6. GABA antagonists: acetoprole, endosulfan, ethiprole, mers according to the invention as crystallization inhibitors 35 fipronil, vaniliprole; and at least one sparingly soluble pesticide. A.7. macrolid insecticides: abamectin, emamectin, milbe The term “sparingly soluble pesticide” refers here to a mectin, lepimectin, spinosad; pesticide that is sparingly soluble in water. According to the A.8. METI I acaricides: fenazaquin, pyridaben, tebufen invention, as already mentioned above, the term "sparingly pyrad, tolfenpyrad; soluble in water here also comprises virtually insoluble sub- 40 A.9. METI II and III compound: acequinocyl, fluacyprim, stances and means that for a solution of the pesticide in water hydramethylnon, at 20°C., at least 30 to 100 g of water is required per g of pesticide, preferably at least 100 g of water per 1 g of pesti A.10. uncoupler compounds: chlorfenapyr; cide. In the case of virtually insoluble pesticides, at least 10 A.11. inhibitors of oxidative phosphorylation: cyhexatin, 000 g of water per g of substance are required. 45 diafenthiuron, fenbutatin oxide, propargite; Pesticides and agrochemical active ingredients are known A.12. molting disruptor compounds: cryomazine; to the person skilled in the art from the literature. The term "pesticide” means here at least one active ingredient selected A.13. inhibitors of mixed function oxidase: piperonyl from the group of insecticides, fungicides, herbicides and/or butoxide; safeners (see Pesticide Manual, 13th Ed. (2003)). 50 A. 14. Sodium channel blockers: indoxacarb, metaflumi Examples of sparingly soluble pesticides are insecticides, Zone; fungicides, herbicides and/or safeners are listed below: A. 15. Various: benclothiaz, bifenazate, flonicamid, pyrida The following list of sparingly soluble insecticides indi lyl, pymetrozine, Sulfur, thiocyclam and aminoisothiazole cates possible active ingredients, but should not be restricted compounds of formula T, to these: 55 A.l. organo (thio)phosphates: azinphos-methyl, chlorpyri fos, chlorpyrifos-methyl, chlorfenvinphos, diazinon, disulfo (T2) ton, ethion, fenitrothion, fenthion, isoxathion, malathion, methidathion, methyl-parathion, Oxydemeton-methyl, C Ri paraoxon, parathion, phenthoate, phosalone, phosmet, phos- 60 N phamidon, phorate, phoxim, pirimiphos-methyl, profenofos, s N prothiofos, Sulprophos, tetrachlorvinphos, terbufos, triazo phos, trichlorfon; NN-S O OX-R, A.2. carbamates: alanycarb, bendiocarb, benfuracarb, car baryl, carbofuran, carbosulfan, fenoxycarb, furathiocarb. 65 methiocarb, methomyl, oxamyl, pirimicarb, thiodicarb, triaz where R is CHOCHCH or H and R is CFCFCF or amate, CH-CH(CH), anthranilamide compounds of formula T US 8,211,469 B2 14 methyl-1H-pyrazole-4-carboxamide, N-(trans-2-bicyclopro (T3) pyl-2-ylphenyl)-3-difluoromethyl-1-methyl-1H-pyrazole-4- carboxamide; carboxylic acid morpholides: dimethomorph, flumorph; benzoamides: flumetover, fluopicolide (picobenzamid), Zoxamide; in a further embodiment, one example of benzoamide is N-(3-ethyl-3,5,5-trimethylcyclohexyl)- 3-formylamino-2-hydroxybenzamide: other carboxamides: carpropamid, diclocymet, mandipro 10 pamid, N-(2-(4-3-(4-chloro-phenyl)prop-2-ynyloxy 3-methoxyphenyl)ethyl)-2-methanesulfonylamino-3- where B1 is hydrogen or chlorine, B2 is bromine or CF3, and methyl-butyramide, N-(2-(4-3-(4-chlorophenyl)prop RB is CH3 or CH(CH3)2, and malononitrile compounds as 2-ynyloxy-3-methoxyphenyl)ethyl)-2- described in JP 2002 284608, WO 02/89579, WO 02/90320, ethanesulfonylamino-3-methylbutyramide, N-(3',4'- WO 02/90321, WO 04/06677, WO 04/20399, or JP 2004 15 dichloro-5-fluorobiphenyl-2-yl)-3-difluoromethyl-1- 99597, N R-2,2-dihalo-1-R"cyclopropanecarboxamide-2- methyl-1H-pyrazole-4-carboxamide and N-(2- (2,6-dichloro-C.C.C.C.-tri-fluoro-p-tolyl)hydrazone O bicyclopropyl-2-yl-phenyl)-3-difluoromethyl-1- N—R-2,2-di(R")propionamide-2-(2,6-dichloro-C.C.C.C.- methyl-1H-pyrazole-4-carboxamide; in a further trifluoro-p-tolyl)hydrazone, in which R" is methyl or ethyl, embodiment examples of other carboxamides are halo is chlorine or bromine, R" is hydrogen or methyl and R" oxytetracyclin, silthiofam, N-(6-methoxypyridin-3-yl) is methyl or ethyl. cyclopropanecarboxamide. The following list of sparingly soluble fungicides indicates 3. Azoles possible active ingredients, but should not be limited to these: triazoles: bitertanol, bromuconazole, cyproconazole, 1. Strobilurins difenoconazole, diniconazole, enilconazole, epoxicona aZoxystrobin, dimoxystrobin, enestroburin, fluoxastrobin, 25 Zole, fenbuconazole, flusilaZole, fluguinconazole, flutri kresoxim-methyl, metominostrobin, picoxystrobin, pyra afol, hexaconazol, imibenconazole, ipconazole, met clostrobin, trifloxystrobin, orysastrobin, methyl (2-chloro-5- conazole, myclobutanil, penconazole, propiconazole, 1-(3-methylbenzyloxyimino)ethylbenzyl)carbamate, prothioconazole, Simeconazole, tebuconazole, tetra methyl (2-chloro-5-1-(6-methylpyridin-2-ylmethoxyimino) conazole, triadimenol, triadimefon, triticonazole; ethylbenzyl)carbamate, methyl 2-(ortho((2,5-dimethyl-phe 30 imidazoles: cyaZofamid, imazalil, pefurazoate, prochlo nyloxymethylene)phenyl)-3-methoxyacrylate; raz, triflumizole; 2. Carboxamides benzimidazoles: benomyl, carbendazim, fuberidazole, carboxanilides: benalaxyl, benodanil, boScalid, carboxin, thiabendazole; mepronil, fenfuram, fenhex-amid, flutolanil, furamet 35 others: ethaboxam, etridiazole, hymexazole; pyr, metalaxyl, ofurace, oxadixyl, oxycarboxin, penthi 4. Nitrogen-Containing Heterocyclyl Compounds: opyrad, thifluzamide, tiadinil, N-(4-bromobiphenyl-2- pyridines: fluaZinam, pyrifenox, 3-5-(4-chlorophenyl)-2, yl)-4-difluoromethyl-2-methylthiazole-5-carboxamide, 3-dimethylisoxazolidin-3-ylpyridine; N-(4-trifluoromethylbiphenyl-2-yl)-4-difluoromethyl pyrimidines: bupirimate, cyprodinil, ferimZone, fenarimol, 2-methylthiazole-5-carboxamide, N-(4-chloro-3'-fluo 40 mepanipyrim, nuarimol, pyrimethanil; robiphenyl-2-yl)-4-difluoromethyl-2-methylthiazole piperazines: triforine; 5-carboxamide, N-(3',4'-dichloro-4-fluorobiphenyl-2- pyrroles: fludioxonil, fenpiclonil; yl)-3-difluoromethyl-1-methyl-pyrazole-4- morpholines: aldimorph, dodemorph, fempropimorph, tri carboxamide, N-(2-cyanophenyl)-3,4- demorph; dichloroisothiazole-5-carboxamide: N-(3',4'-dichloro 45 dicarboximides: iprodione, procymidone, VincloZolin; 5-fluorobiphenyl-2-yl)-3-difluoromethyl-1- others: acilbenzolar-S-methyl, anilazin, captan, captafol. methylpyrazole-4-carboxamide, N-(2-bicyclopropyl-2- dazomet, diclomeZine, fenoxanil, folpet, fenpropidin, ylphenyl)-3-difluoromethyl-1-methyl-1H-pyrazole-4- famoxadone, fenamidone, octhillinone, probenazole, carboxamide; produinazid, quinoxyfen, tricyclazole, 5-chloro-7-(4- in a further embodiment, examples of carboxanilides are 50 methylpiperidin-1-yl)-6-(2,4,6-trifluorophenyl)12.4 benalaxyl-M, bixafen, isotianil, kiralaxyl, tecloftalam, triazolo 1.5-alpyrimidine, 2-butoxy-6-iodo-3-propyl 2-amino-4-methylthiazole-5-carboxanilide, 2-chloro-N-(1, chromen-4-one, N-dimethyl-3-(3-bromo-6-fluoro-2- 1,3-tri-methylindan-4-yl)nicotinamide, N-(3',4'-dichloro-5- fluorobiphenyl-2-yl)-3-difluoromethyl-1-methyl-1H-pyra methylindole-1-sulfonyl) 1,2,4-triazole-1- Zole-4-carboxamide, N-2-(1,3-dimethylbutyl)phenyl-5- Sulfonamide; fluoro-1,3-dimethyl-1H-pyrazole-4-carboxamide, N-(4- 55 5. Carbamates and Dithiocarbamates chloro-3',5-difluorobiphenyl-2-yl)-3-difluoromethyl-1- carbamates: diethofencarb, flubenthiavalicarb, iprovali methyl-1H-pyrazole-4-carboxamide, N-(4-chloro-3',5- carb, propamocarb, methyl 3-(4-chlorophenyl)-3-(2- difluorobiphenyl-2-yl)-3-trifluoromethyl-1-methyl-1H isopropoxycarbonylamino-3-methylbutyrylamino)pro pyrazole-4-carboxamide, N-(3',4'-dichloro-5- pionate, 4-fluorophenyl N-(1-(1-(4-cyanophenyl) fluorobiphenyl-2-yl)-3-trifluoromethyl-1-methyl-1H 60 ethanesulfonyl)but-2-yl)carbamate; pyrazole-4-carboxamide, N-(3',5-difluoro-4'- 6. Other Fungicides methylbiphenyl-2-yl)-3-difluoromethyl-1-methyl-1H organometallic compounds: fentin salts; pyrazole-4-carboxamide, N-(3',5-difluoro-4'- Sulfur-containing heterocyclyl compounds: isoprothi methylbiphenyl-2-yl)-3-trifluoromethyl-1-methyl-1H olane, dithianon; pyrazole-4-carboxamide, N-(2-bicyclopropyl-2-yl-phenyl)- 65 organophosphorus compounds: edifenphos, fosetyl, fos 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxamide, etyl-aluminum, iprobenfos, pyrazophos, tolclofoS-me N-(cis-2-bicyclopropyl-2-ylphenyl)-3-difluoromethyl-1- thyl, phosphorous acid and its salts; US 8,211,469 B2 15 16 organochlorine compounds: thiophanate methyl, chlo R. R" are hydrogen, halogen, C, -Co-alkyl, C-C-ha rothalonil, dichlofluanid, tolylfluanid, flusulfamide, loalkyl, C-C-alkoxy, C-C-halo-alkoxy, C-C-alkylthio. phthalide, hexachlorbenzene, pencycuron, quintoZene; C-C-alkylsulfinyl or C-C-alkylsulfonyl: nitrophenyl derivatives: binapacryl, dinocap, dinobuton; R is a heterocyclic radical from the group consisting of others: spiroxamine, cyflufenamid, cymoxaniil, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isoxazol-3-yl, isox metrafenone. azol-4-yl, isoxazol-5-yl 4,5-dihydroisoxazol-3-yl 4,5-dihy The following list of sparingly solubleherbicides indicates droisoxazol-4-yland 4,5-dihydroisoxazol-5-yl, in which the possible active ingredients, but should not be limited to these: specified radicals can carry one or more Substituents, for Compounds which inhibit the biosynthesis of lipids, for example may be mono-, di-, tri- or tetra-substituted by halo example chlorazifop, clodinafop, clofop, cyhalofop, ciclo 10 gen, C-C-alkyl, C-C-alkoxy, C-C-haloalkyl, C-Ca-ha fop, fenoxaprop, fenoxaprop-p, fenthiaprop, fluazifop, flu loalkoxy or C-C-alkylthio; azifop-P, haloxyfop, haloxyfop-P, isoxapyrifop, metamifop, R'-hydrogen, halogen or C1-Co-alkyl; propaquizafop, quizalofop, quizalofop-P trifop, and their R’’=C-C-alkyl: esters, butroxydim, cycloxydim, profoxydim, Sethoxydim, 15 R'-hydrogen or C-C-alkyl. tepraloxydim, tralkoxydim, butylate, cycloat, diallat, dime If the pH is <8. piperat, EPTC, esprocarb, ethiolate, isopolinate, methioben Mitosis inhibitors such as benfluralin, butralin, dinitra carb, molinate, orbencarb, pebulate, prosulfocarb, Sulfallat, mine, ethalfluralin, fluchloralin, isopropalin, methalpropalin, thiobencarb, thiocarbazil, triallat, Vernolat, benfuresat, etho nitralin, oryzalin, pendimethalin, prodiamine, profluralin, tri fumesat und bensulid; ALS inhibitors, such as amidosulfuron, azimsulfuron, ben fluralin, amiprofoS-methyl, butamifos, dithiopyr, thiazopyr, Sulfuron, chlorimuron, chlorSulfuron, cinosulfuron, cycloSul propyZamide, chlorthal, carbetamide, chlorpropham and famuron, ethametSulfuron, ethoxysulfuron, flaZaSulfuron, propham; fluipyrsulfuron, foramsulfuron, halosulfuron, imaZoSulfuron, VLCFA inhibitors such as acetochlor, alachlor, butachlor, iodosulfuron, mesosulfuron, metSulfuron, nicosulfuron, oxa butenachlor, delachlor, diethatyl, dimethachlor, dimethena Sulfuron, primisulfuron, prosulfuron, pyrazosulfuron, rim 25 mid, dimethenamid-p, metaZachlor, metolachlor, S-meto sulfuron, sulfometuron, sulfosulfuron, thifensulfuron, tria lachlor, pretilachlor, propisochlor, prynachlor, terbuchlor, sulfuron, tribenuron, trifloxysulfuron, triflusulfuron, thenylchlor, xylachlor, CDEA, epronaz, diphenamid, tritosulfuron, imazamethabenZ, imaZamox, imazapic, imaza napropamide, naproanilide, pethoxamid, flufenacet, mefen pyr, imaZaquin, imazethapyr, cloranSulam, dicloSulam, flo acet, fentraZamide, anilofos, piperophos, cafenstrole, indano rasulam, flumetSulam, metoSulam, penoXSulam, bispyribac, 30 fan and tridiphan; pyriminobac, propoxycarbazone, flucarbazone, pyriben Inhibitors for the biosynthesis of cellulose, such as dichlo Zoxim, pyriftalid and pyrithiobac; if the pH is <8; benil, chlorthiamid, isoxaben and flupoxam; Compounds which inhibit the photosynthesis, such as atra Herbicides such as dinofenat, dinoprop, dinosam, dinoseb, ton, atrazine, ametryne, aziprotryne, cyanazine, cyanatryn, dinoterb, DNOC, etinofen and medinoterb: chlorazine, cyprazine, desmetryne, dimethametryne, dipro 35 Furthermore: benzoylprop, flamprop, flamprop-M, bro petryn, eglinazine, ipazine, mesoprazine, methometon, mobutide, chlorflurenol, cinmethylin, methyldymron, eto methoprotryne, procyazine, proglinazine, prometon, prom benzanid, pyributicarb, oxaziclomefone, triaziflam and etryne, propazine, Sebuthylazine, secbumeton, Simazine, sim methyl bromide. eton, simetryne, terbumeton, terbuthylazine and terbutryne; The following list indicates possible sparingly soluble Protoporphyrinogen-IX oxidase inhibitors, such as acif 40 safeners, but should not be restricted to these: luorfen, bifenox, cchlomethoxyfen, chlornitrofen, ethoxyfen, benoxacor, cloquintocet, cyometrinil, dicyclonon, dietho fluorodifen, fluoroglycofen, fluoronitrofen, fomesafen, fury late, fenchlorazole, fenclorim, flurazole, fluxofenim, furila loxyfen, halosafen, lactofen, nitrofen, nitrofluorfen, oxyfluo Zole, isoxadifen, mefenpyr, mephenate, naphthalic anhy rfen, fluaZolate, pyraflufen, cinidon-ethyl, flumiclorac, flumi dride, 2.2.5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine oxazin, flumipropyn, fluthiacet, thidiazimin, oxadiazon, 45 (R-29148), 4-(dichloro-acetyl)-1-oxa-4-azaspiro4.5 decane oxadiargyl, azafenidin, carfentraZone, SulfentraZone, pentox (AD-67: MON 4660) and oxabetrinil. aZone, benzfendizone, butafenacil, pyraclonil, profluaZol. Preferred fungicides are triazoles such as bitertanol, bro flufenpyr, flupropacil, nipyraclofen and etnipromid; muconazole, cyproconazole, difenoconazole, diniconazole, Herbicides such as metflurazon, norflurazon, flufenican, enilconazole, epoxyconazole, fenbuconazole, flusilaZole, diflufenican, picolinafen, beflubutamid, fluridone, fluoro 50 fluquinconazole, flutriafol, hexaconazol, imibenconazole, chloridone, flurtamone, mesotrione, Sulcotrione, isoxachlor tole, isoxaflutole, benzofenap, pyrazolynate, pyrazoxyfen, ipconazole, metconazole, myclobutanil, penconazole, propi benzobicyclon, amitrole, clomaZone, aclonifen, 4-(3-trifluo conazole, prothioconazole, Simeconazole, tebuconazole, tet romethylphenoxy)-2-(4-trifluoromethyl-phenyl)pyrimidine, raconazole, triadimenol, triadimefon, triticonazole, strobilu and 3-heterocyclyl-substituted benzoyl derivatives of the for rine Such as azoxystrobin, dimoxystrobin, enestroburin, 55 fluoxastrobin, kresoxim-methyl, metominostrobin, picox mula (cf. WO-A-96/26202, WO-A-97/41116, WO-A-97/ yStrobin, pyraclostrobin, trifloxystrobin, orysastrobin, 41117 and WO-A-97/41118) methyl (2-chloro-5-1-(3-methylbenzyloxyimino)ethylben Zyl)carbamate, methyl (2-chloro-5-1-(6-methylpyridin-2- R13 O R8 ylmethoxyimino)ethylbenzyl)carbamate, methyl 2-(ortho R9 60 ((2,5-dimethylphenyloxymethylene)phenyl)-3- methoxyacrylate, and 5-chloro-7-(4-methyl-piperidin-1-yl)- NY 6-(2,4,6-trifluorophenyl) 1,2,4-triazolo 1.5-alpyrimidine / OH R10 and boscalid. R12 R11 Very particularly preferred fungicides are epoxyconazole, 65 metconazole, pyraclostrobin, kresoxim-methyl and 5-chloro in which the substituents R to R' have the following mean 7-(4-methylpiperidin-1-yl)-6-(2,4,6-trifluoro-phenyl) 1.2.4 ings: triazolo 1.5-alpyrimidine and boscalid. US 8,211,469 B2 17 18 Preferred insecticides are metaflumizon, fipronil and Such as ammonium sulfate, ammonium phosphate, ammo alpha-cypermethrin. nium nitrate, ureas and vegetable products such as cornmeal, In a further preferred embodiment, mixtures comprising at bark dust, sawdust, nutshell meal, cellulose powder or other least two different triazoles are preferred, in particular mix Solid carriers. tures comprising metconazole and epoxyconazole, metcona Suitable surface-active Substances (adjuvants, wetting Zole and prothioconazole, or epoxyconazole and prothio agents, adhesives, dispersants or emulsifiers) are the alkali conazole. metal salts, alkaline earth metal salts, ammonium salts of In a further preferred embodiment, mixtures comprising at aromatic Sulfonic acids, e.g. lignin (Borresperse grades Bor least one triazole and at least one strobilurin are preferred. regaard), phenol, naphthalene (Morwet grades, Akzo Nobel) Specifically, mixtures comprising pyraclostrobin and epoxy 10 and dibutylnaphthalenesulfonic acid (Nekal grades BASF), conazole, and mixtures comprising pyraclostrobin and met and of fatty acids, alkyl- and alkylarylsulfonates, alkyl Sul conazole are preferred. fates, lauryl ether sulfates and fatty alcohol sulfates, and salts In a further preferred embodiment, mixtures comprising at of Sulfated hexa-, hepta- and octadecanols, and offatty alco least one triazole and at least one carboxamide are preferred. hol glycol ethers, condensation products of Sulfonated naph In particular, preference is given to mixtures which comprise 15 thalene and its derivatives with formaldehyde, condensation at least one triazole, at least one carboxamide and at least one products of naphthalene or of naphthalenesulfonic acids with strobilurin. phenol and formaldehyde, polyoxyethylene octyl phenol In the agrochemical preparations, the mass ratio of poly ether, ethoxylated isooctyl-, octyl- or nonylphenol, alkylphe meractive ingredient is 1:10 (w/w) to 100:1 (w/w), prefer nyl, tributylphenyl polyglycol ethers, alkylaryl polyether ably 1:2 (w/w) to 50:1 (w/w), particularly preferably 1:1 alcohols, isotridecyl alcohol, fatty alcohol ethylene oxide (w/w) to 10:1 (w/w), particularly preferably 2:1 (w/w) to 10:1 condensates, ethoxylated ricinus oil, polyoxyethylene or (w/w). polyoxypropylene alkyl ethers, lauryl alcohol polyglycol The agrochemical preparations can furthermore also com ether acetate, Sorbitol esters, lignin Sulfite spent liquors, and prise auxiliaries customary for the formulation of pesticides, proteins, denatured proteins, polysaccharides (e.g. methyl the choice of auxiliaries being governed by the particular 25 cellulose), hydrophobically modified starches, polyvinyl application form and the active ingredient. alcohol (Mowiol grades Clariant), polycarboxylate (BASF As a rule, the amount of auxiliaries used is between 0 and Sokalan grades), polyalkoxylates, polyvinylamine (BASF 60% by weight, preferably 0.1 and 30% by weight. Lupamin grades), polyethyleneimine (BASF Lupasol Examples of auxiliaries suitable for the formulation of grades), polyvinylpyrrolidone and copolymers thereof. pesticides are solvents, solid carriers, Surface-active Sub 30 Examples of various types of agrochemical preparations in stances (such as further solubilizers, protective colloids, wet which the copolymers according to the invention can be used ting agents and adhesives), organic and inorganic thickeners, are pastes, pastilles, wettable powders, dusts (WP, SP. SS, bactericides, antifreezes, antifoams. WS, DP DS) or granules (WG, GR, FG, GG, MG) or tablet Examples of thickeners (i.e. compounds which impart a preparations (TB, WT), which may either be soluble or dis modified flow behavior to the formulation, i.e. high viscosity 35 persible (wettable) in water. in the resting state and low viscosity in the moving State) are The agrochemical preparations (e.g. OD, FS, WG, SG, WP. polysaccharides, and also organic and inorganic layered min SPSS, WS)) are generally used in diluted form. Formulation erals such as Xanthan gum (Kelzan(R) from Kelco), types such as DP DS, GR, FG, GG, MG are usually used neat. Rhodopol.R. 23 (Rhone Poulenc) or Veegum R. (R.T. Vander Preference is given to the above defined types of agro bilt) or Attaclay (R) (Engelhardt). 40 chemical preparations WG, WP, GR, WT and TB. Examples of antifoams are silicone emulsions (such as, for The production of agrochemical formulations and the tech example, Silikon(R) SRE, Wacker or Rhodorsil R from nology required for this is known to the person skilled in the Rhodia), long-chain alcohols, fatty acids, salts of fatty acids, art (see U.S. Pat. No. 3,060,084, EP-A 707445 (for liquid organofluorine compounds and mixtures thereof. concentrates), Browning, "Agglomeration’, Chemical Engi Examples of bactericides are bactericides based on dichlo 45 neering, Dec. 4, 1967, 147-48, Perry's Chemical Engineers rophen and benzyl alcohol hemiformal (Proxel(R) from ICI or Handbook, 4th Ed., McGraw-Hill, New York, 1963, pp. 8-57 Acticide(R) RS from Thor Chemie and Kathon(R) MK from and ff. WO 91/13546, U.S. Pat. No. 4,172,714, U.S. Pat. No. Rohm & Haas), and isothiazolinone derivatives, such as alky 4,144,050, U.S. Pat. No. 3,920,442, U.S. Pat. No. 5,180,587, lisothiazolinones and benzisothiazolinones (Acticide MBS U.S. Pat. No. 5,232,701, U.S. Pat. No. 5,208,030, GB 2,095, from Thor Chemie). 50 558, U.S. Pat. No. 3.299,566, Klingman, Weed Control as a Examples of antifreezes are ethylene glycol, propylene Science, John Wiley and Sons, Inc., New York, 1961, Hance glycol, urea or glycerol. et al., Weed Control Handbook, 8th Ed., Blackwell Scientific Suitable solvents are organic solvents such as mineral oil Publications, Oxford, 1989 and Mollet, H., Grubemann, A., fractions of medium to high boiling point, such as kerosene Formulation technology, Wiley VCH Verlag GmbH. Wein and diesel oil, also coaltar oils, and oils of vegetable or animal 55 heim (Federal Republic of Germany), 2001). origin, aliphatic, cyclic and aromatic hydrocarbons, e.g. par All of the embodiments of the abovementioned agrochemi affins, tetrahydronaphthalene, alkylated naphthalenes and cal preparations are referred to below as "agrochemical derivatives thereof, alkylated benzenes and derivatives preparations according to the invention'. thereof, alcohols, such as methanol, ethanol, propanol, The present invention also claims methods of controlling butanol and cyclohexanol, ketones, such as cyclohexanone, 60 undesired plant growth wherein the undesired plants, the strongly polar solvents, for example amines Such as N-meth ground on which the undesired plants grow, or their seeds are ylpyrrolidone, and mixtures of the above-mentioned solvents treated with an agrochemical preparation according to the and water, and also mixtures of water and organic solvents. invention. Solid carriers are mineral earths such as silicas, silica gels, Furthermore, the present invention claims methods of con silicates, talc, kaolin, limestone, lime, chalk, bolus, loess, 65 trolling undesired insect or mite attack on plants and/or for clay, dolomite, diatomaceous earth, calcium sulfate and mag controlling phytopathogenic fungi, wherein the fungi/insects, nesium sulfate, magnesium oxide, ground plastics, fertilizers, their habitat or the plants or ground to be protected against US 8,211,469 B2 19 20 fungalorinsect attack and the plants, the ground on which the siliensis, Hylobius abietis, Hypera brunneipennis, Hypera plants grow, or seeds thereofare treated with an agrochemical postica, Ips typographus, Lema bilineata, Lema melanopus, preparation according to the invention. Leptinotarsa decemlineata, Limonius Californicus and other The term phytopathogenic fungi describes, but is not Limonius spp., Lissorhoptrus Oryzophilus, Listronotus bonar restricted to, the following species: Alternaria spp. on rice, 5 iensis, Melanotus communis and other Melanotus spp. Vegetables, soybeans, rapeseed, Sugar beet and fruits, Apha Melligethes aeneus, Melolontha hippocastani, Melolontha nomyces spp. on Sugar beet and vegetables, Bipolaris and melolontha, Oulema Oryzae, Ortiorrhynchus sulcatus, Drechslera spp. corn, cereals, rice and cultivated lawns, Oryzophagus Oryzae, Otiorrhynchus ovatus, Oulema Oryzae, Blumeria graminis (powdery mildew) on cereals, Botrytis Phaedon cochleariae, Phyllotreta chrysocephala, Phyllo cinerea (gray mold) on Strawberries, vegetables, cultivated 10 phaga cuyabana and other Phyllophaga spp., Phyllopertha flowers, grapes, Bremia lactucae on lettuce, Cercospora spp. horticola, Phyllotreta memorum, Phyllotreta striolata, and on corn, soybeans and Sugar beet, Cochliobolus spp. on corn, other Phyllotreta spp., Popillia japonica, Promecops carini cereals, rice (e.g. Cochliobolus sativus oncereals, Cochliobo collis, Premnotrypes voraz, Psylliodes spp., Sitona lineatus, lus miyabeanus on corn), Colletotrichum spp. on Soybeans Sitophilus granaria, Sternechus pinguis, Sternechus subsig and cotton, Drechisera spp. on cereals and corn, Exserohlilum 15 natus, and Tanymechus palliatus and other Tany mechus spp. spp. on corn, Erysiphe cichoracearum and Sphaerotheca Flies (Diptera), for example Agromyza Oryzea, Chrysomya fiuliginea on cucumbers, Erysiphe necator on grapes, bezziana, Chrysomya hominivorax, Chrysomya macellaria, Fusarium and Verticillium spp. on various plants, Gaeuman Contarinia sorghicola, Cordylobia anthropophaga, Dacus nomyces graminis on cereals, Gibberella spp. on cereals and cucurbitae, Dacus oleae, Dasineura brassicae, Delia rice (e.g. Gibberellafiujikuroi on rice, Gibberella zeae on antique, Della coarctata, Delia platura, Delia radicum, Fan cereals), grainstaining complex on rice, Microdochium nivale nia canicularis, Gasterophilus intestinalis, Geomyza on cereals, Mycosphaerella spp. on cereals, bananas and pea Tripunctata, Glossina morsitans, Haematobia irritans, Hap nuts, Phakopsora pachyrhizi and Phakopsora meibomiae on lodiplosis equestris, Hypoderma lineata, Liriomyza sativae, Soybeans, Phomopsis spp. on Soybeans and Sunflowers, Phy Liriomyza trifolii, Lucilia caprina, Lucilia cuprina, Lucilia tophthora infestans on potatoes and tomatoes, Plasmopara 25 sericata, Lycoria pectoralis, Mayetiola destructor; Muscina viticola on grapes, Podosphaera leucotricha on apples, stabulans, Oestrus ovis, Opomyza florum, Oscinella frit, Pseudocercosporella herpotrichoides on wheat and barley, Pegomya hysocyani, Phorbia antiqua, Phorbia brassicae, Pseudoperonospora spp. on hops and cucumbers, Puccinia Phorbia coarctata, Progonya levoscianil, Psila rosae, spp. on cereals and corn, Pyrenophora spp. on cereals, Rhagoletis cerasi, Rhagoletis pomonella, Tabanus bovinus, Pyricularia Oryzae on rice, Cochliobolus miyabeanus and 30 Tetanops myopaeformis, Tipula oleracea and Tipula palu Corticium Sasakii (Rhizoctonia Solani), Fusarium semitec dosa, tum (and/or moniliforme), Cercospora Oryzae, Sarocladium Heteroptera (Heteroptera), for example Acrosternum Oryzae, Sattenuatum, Entyloma Oryzae, Gibberellafiujikuroi hilare, Blissus leucopterus, Cicadellidae for example (bakanae), Grainstaining complex (various pathogens), Bipo Empoasca fabae, Chrysomelidae, Cyrtopeltis notatus, laris spp., Drechslera spp. and Pythium and Rhizoctonia spp. 35 Delpahcidae, Dysdercus cingulatus, Dysdercus intermedius, on rice, corn, cotton, Sunflowers, rapeseed (canola, oilseed Eurygaster integriceps, Euschistus impictiventris, Leptoglo rape), vegetables, lawns, nuts and other plants, Rhizoctonia ssus phyllopus, Lygus lineolaris, Lygus pratensis, Nephotet Solani on potatoes, Sclerotinia spp. on types of rapeseed tix spp., Nezara viridula, Pentatomidae, Piesma quadrata, (canola/oilseed rape) and Sunflowers, Septoria tritici and Solubea insularis and Thyanta perditor, Stagonospora nodorum on wheat, Uncinula necator on 40 Aphids and other homoptera, for example Acyrthosiphon grapes, Sphacelotheca reiliana on corn, Thievaliopsis spp. on Onobrychis, Adelges laricis, Aphidula masturtii, Aphis fabae, Soybeans and cotton, Tilletia spp. on cereals, Ustilago spp. on Aphis forbesi, Aphis glycines, Aphis gossypii, Aphis grossu cereals, corn, Sugar beet and Venturia spp. (scab) on apples lariae, Aphis pomi, Aphis Schneideri, Aphis spiraecola, Aphis and pears; Sambuci, Acyrthosiphon pisum, Aulacorthum Solani, Brachy The term undesired insects or mites describes, but is not 45 caudus cardui, Brachycaudus helichrysi, Brachycaudus per restricted to, the following genera: sicae, Brachycaudus prunicola, Brevicoryne brassicae, Cap Millipedes (Diplopoda), for example Blaniulus spp itophorus horni, Cerosipha gossypii, Chaetosiphon Ants (Hymenoptera), for example Atta capiguara, Atta fragaefolii, Cryptomyzus ribis, Dreyfusia nordmannianae, cephalotes, Atta laevigata, Atta robusta, Atta sexdens, Atta Dreyfusia piceae, Dysaphis radicola, Dysaulacorthum pseu texana, Monomorium pharaonis, Solenopsis geminata, Sole 50 doSolani, Dysaphis plantaginea, Dysaphis pyri, Empoasca nopsis invicta, Pogonomyrmex spp and Pheidole mega fabae, Hyalopterus pruni, Hyperomyzus lactucae, Macrosi Cephala, phum avenae, Macrosiphum euphorbiae, Macrosiphon Beetles (Coleoptera), for example Agrilus sinuatus, Agri rosae, Megoura viciae, Melanaphis pyrarius, Metopol otes lineatus, Agriotes obscurus and other Agriotes spp. Ophium dirhodium, Myzodes (Myzus) persicae, Myzus asca Amphimalus solstitialis, Anisandrus dispar; Anthonomus 55 lonicus, Myzus cerasi, Myzus varians, Nasonovia ribis-nigri, grandis, Anthonomus pomorum, Aracanthus morei, Atomaria Nilaparvata lugens, Pemphigus bursarius, Pemphigus popu linearis, Blapstinus spp., Blastophagus piniperda, Blitophaga livenae, and other Pemphigus spp., Perkinsiella saccharicida, undata, Bothy noderes punciventris, Bruchus rufimanus, Bru Phorodon humuli, Psyllidae, for example Psylla mali, Psylla chus pisorum, Bruchus lentis, Byctiscus betulae, Cassida piri and other Psylla spp., Rhopalomyzus ascalonicus, Rho nebulosa, Cerotoma trifiurcata, Ceuthorrhynchus assimilis, 60 palosiphum maidis, Rhopalosiphum padi, Rhopalosiphum Ceuthorrhynchus mapi, Chaetocnema tibialis, Conoderus insertum, Sappaphis mala, Sappaphis mali, Schizaphis vesperitnus and other Conoderus spp., Conorhynchus mendi graminum, Schizoneura lanuginosa, Sitobion avenae, Tri cus, Crioceris asparagi, Cylindrocopturus adspersus, aleurodes vaporariorum, Toxoptera aurantiand, und Viteus Diabrotica (longicornis) barberi, Diabrotica semi-punctata, vitifolii, Lepidoptera, for example Agrotis ypsilon, Agrotis Diabrotica speciosa, Diabrotica undecimpunctata, 65 segetum and other Agrotis spp., Alabama argilacea, Anticar Diabrotica virgifera and other Diabrotica spp., Eleodes spp. sia gemmatalis, Argyresthia Conjugella, Autographa gamma, Epilachna varivestis, Epitrix hirtipennis, Eutinobothrus bra Bupalus piniarius, Cacoecia murinana, Capua reticulana, US 8,211,469 B2 21 22 Cheimatobia brumata, Chilo suppresalis and other Chilo spp. Saphelenchus spp., ring nematodes, Criconema spp., Cricone Choristoneura filmiferana, Choristoneura Occidentalis, Cir mella spp., Criconenoides spp., Mesocriconema spp.; stem and phis unipuncta, Cnaphlocrocis medinails, Cydia pomonella, bulb nematodes, Dity lenchus destructor, Dity lenchus dipsaci Dendrolimus pini, Diaphania initidalis, Diatraea grandi and other Dity lenchus spp., Awl nematodes, Dolichodorus Osella, Earias insulana, Elasmopalpus lignosellus, Eupo spp.; spiral nematodes, Heliocotylenchus mutlicinctus and eclia ambiguella, Euxoa spp. Evetria bouliana, Feltia subter other Helicotylenchus spp.; sheath and sheathoid nematodes, ranea, Galleria mellonella, Grapholitha funebrana, Hemicycliophora spp and Hemicriconenoides spp., Hirsh Grapholitha molesta, Heliothis armigera, Heliothis vire manniella spp.; lance nematodes, Hoploaimus spp., false root scens, Heliothis zea, Hellula undais, Hibernia defoliaria, knot nematodes, Nacobbus spp., needle nematodes, Longi Hyphantria cunea, Hyponomeuta malinellus, Keiferia lyco 10 dorus elongatus and other Longidorus spp.; lesion nematodes, persicella, Lambdina fiscellaria, Laphygma exigua, Lerodea Pratylenchus neglectus, Pratylenchus penetrans, Pratylen eufala, Leucoptera coffeella, Leucoptera scitella, Lithocolle chus curvillatus, Pratylenchus goodeyl and other Pratylen tis blancardella, Lobesia botrana, Loxostege Sticticalis, chus spp., Burrowing nematodes, Radopholus similis und Lymantria dispar, Lymantria monacha, Lyonetia clerkella, andere Radopholus spp., Reniform nematodes, Rotylenchus Malacosoma neustria, Mamestra brassicae, Momphidae, 15 robustus and other Rotylenchus spp., Scutellonema spp.; Orgvia pseudotsugata, Ostrinia nubilalis, Panolis flammea, Stubby root nematodes, Trichodorus primitivus and other Pectinophora gossypiella, Peridroma Saucia, Phalera Trichodorus spp., Paratrichodorus spp., Stunt nematodes, bucephala, Phthorimaea operculella, Phyllocnistis citrella, Tvlenchorhynchus claytoni, Tilenchorhynchus dubius and Pieris brassicae, Plathypena scabra, Plutella xylostella, other Tilenchorhynchus spp., Citrus nematodes, Tilenchulus Pseudoplusia includens, Rhyacionia frustrana, Scrobi spp.; Dagger nematodes, Xiphinema spp.; and other plant para palpula absoluta, Sesamia nonagrioides and other Sesamia sitic nematodes. spp., Sitotroga cerealella, Sparganothis pilleriana, Control of undesired plant growth means the control/de Spodoptera frugiperda, Spodoptera littoralis, Spodoptera struction of plants which grow in places where they are litura, Thaumatopoea pitvocampa, Tortrix viridana, Trichop undesired, for example lusia ni and Zeiraphera Canadensis, 25 Dicotyledonous plants of the species: Sinapis, Lepidium, Orthoptera, for example, Acrididae, Acheta domestica, Galium, Stellaria, Matricaria, Anthemis, Galinsoga, Che Blatta Orientalis, Blattella germanica, Forficula auricularia, nopodium, Urtica, Senecio, Amaranthus, Portulaca, Gryllotalpa gryllotalpa, Locusta migratoria, Melanoplus Xanthium, Convolvulus, Ipomoea, Polygonum, Sesbania, bivilitatus, Melanoplus femur-rubrum, Melanoplus mexica Ambrosia, Cirsium, Carduus, Sonchus, Solanum, Rorippa, nus, Melanoplus sanguinipes, Melanoplus spretus, Noma 30 Rotala, Lindernia, Lamium, Veronica, Abutilon, Emex, dacris Septemfasciata, Periplaneta americana, Schistocerca Datura, Viola, Galeopsis, Papaver, Centaurea, Trifolium, americana, Schistocerca peregrina, Stauronotus maroccanus Ranunculus, Taraxacum. Monocotyledonous plants of the and Tachycines asynamorus, species: Echinochloa, Setaria, Panicum, Digitaria, Phleum, Termites (Isoptera), for example Calotermes flavicollis, Poa, Festuca, Eleusine, Brachiaria, Lolium, Bromus, Avena, Coptotermes spp. Dalbulus maidis, Leucotermes flavipes, 35 Cyperus, Sorghum, Agropyron, Cynodon, Monochoria, Fin Macrotermes gilvus, Reticulitermes lucifigus and Termes bristyslis, Sagittaria, Eleocharis, Scirpus, Paspalum, Ischae natalensis; mum, Sphenoclea, Dactyloctenium, Agrostis, Alopecurus, Thrips (Thysanoptera) for example Frankliniella fisca, Apera Frankliniella Occidentalis, Frankliniella tritici and other The copolymers according to the invention are character Frankliniella spp., Scirtothrips citri, Thrips oryzae, Thrips 40 ized by a particularly good solubilizing effect. They are also palmi, Thrips simplex and Thrips tabaci, able to form so-called solid solutions with sparingly soluble Arachnoidea, for example arachnids (Acarina), for Substances. According to the invention, Solid solutions is the example of the families Argasidae. Ixodidae and Sarcoptidae, term used to refer to systems in which, upon visual inspection, for example Amblyomma americanum, Amblyomma variega no crystalline fractions of the sparingly soluble Substance are tum, Argas persicus, Boophilus annulatus, Boophilus decol 45 to be seen. Furthermore, upon visual inspection of the stable Oratus, Boophilus microplus, Dermacentor Silvarum, Solid solutions, no amorphous constituents are to be seen Hyalomma truncatum, Ixodes ricinus, Ixodes rubicundus, either. Visual inspection takes place using a light microscope Ornithodorus moubata, Otobius megnini, Dermanyssus at 40 times magnification. gallinae, Psoroptes ovis, Rhipicephalus appendiculatus, Rhi Furthermore, the copolymers according to the invention picephalus evertsi, Sarcoptes scabiei, und Eriophyidae spp 50 are characterized in that they increase the bioavailability of e.g. Aculus Schlechtendali, Phylocoptrata oleivOra und Erio active ingredients. In addition, it is advantageous that the phyes Sheldoni; Tarsonemidae spp e.g. Phytonemus pallidus copolymers according to the invention in agrochemical und Polyphagotarisonemus latus; Tenuipalpidae spp e.g. preparations have extremely low phytotoxicity. Furthermore, Brevipalpus phoenicis, Tetranychidae spp e.g. Tetranychus the copolymers according to the invention are characterized cinnabarinus, Tetranychus kanzawai, Tetranychus pacificus, 55 by a particularly good crystallization-inhibiting effect for Tetranychus tellarius and Tetranychus urticae, Panonychus active ingredients that are sparingly soluble in water. ulmi, Panonychus citri, and Oligonychus pratensis, Hitherto, attempts have been made to solve the problems of Nematodes, in particular plant parasitic nematodes, for solubilization and crystal inhibition using various com example “root knot nematodes, Meloidogyne hapla, Meloid pounds. However, a compound which can solve both prob ogyne incognita, Meloidogyne javanica, and other Meloid 60 lems is desirable. A particular advantage of the copolymers ogyne spp., cyst-forming nematodes, Globodera rostochien according to the invention is that preparations of active ingre sis and other Globodera spp., Heterodera avenae, Heterodera dients that are sparingly soluble in water can now make do glycines, Heterodera Schachili, Heterodera trifolii, and other with just one additive which acts both as solubilizer and as Heterodera spp.; seed gall nematodes, Anguina spp.; stem and crystallization inhibitor. foliar nematodes, Aphelenchoides spp.; sting nematodes, 65 In the examples below, the preparation and use of the Belonolaimus longicaudatus and other Belonolaimus spp.; copolymers according to the invention is explained in more pine nematodes, Bursaphelenchus xylophilus and other Bur detail. US 8,211,469 B2 23 24 EXAMPLES greater the color intensity, the greater the solubilization. The table shows that the PVP homopolymers not according to the Abbreviations invention and the random copolymer dissolve the dye less well than comparable block copolymers according to the VP (N-vinylpyrrolidone) invention. VAc (vinyl acetate) PVP (polyvinylpyrrolidone) PVAc (polyvinyl acetate) AIBN (azobisisobutyronitrile) PVP-b- PVP-b- PVP-b-PVAc (block copolymer of PVP and PVAc) 10 PVAC PVAC DMF (dimethylformamide) PVP K90 PVP K30 PVP K17 Copovidone 80-20 50-50 A) Preparation of the Block Copolymers pale pale pink pale pink pink bright red intense red General Procedure yellow Firstly, 200 g of N-vinylpyrrolidone, 1.76 g of 2-(ethoxy carbonothioyl)thiopropionic acid and 0.15g of AIBN in 200 15 C) Solubilization of Active Ingredient from Solid Solution g of dioxane were mixed and this mixture was heated to 70° Furthermore, the solubilization in water of pharmaceutical C. The mixture was held at this temperature for 8 h, then active ingredients from the Solid solution was investigated at cooled to room temperature and the resulting polymer was precipitated out by adding 100 ml of diethyl ether. 37° C. (*50-50 based on use amounts). The comparison The resulting polymer was then mixed with 50 g of vinyl shows that, in the presence of the block copolymer, six times acetate and 0.05 g of AIBN in 75 g of dioxane and the mixture more active ingredient is solubilized than in the presence of a is heated to 70° C. After 8 h, the solvent was removed in vacuo comparable random copolymer copovidone not according to and the polymer was dried at 70° C. in a vacuum drying the invention. cabinet. 25 Solubilization of Solubilization of clotrimazol estradiol mg/kg mg/kg PVP-PVAc Ex. mol % Solubility in PVP-b-PVAcSO-508 O.O6 O.O6 O use amounts PDI: M. Water Copovidone O.O1 O.O1 30 1 90-10 1.6 148OO soluble 2 80-20 1.8 132OO soluble 3 70-30 2 12900 soluble D) Solubilization of Agrochemical Active Ingredients 4 60-40 1.9 13900 soluble from Solid Solution 5 50-50 2 17600 soluble Solubility in water of the agrochemical active ingredients 5 40-60 2.3 192OO micellarly 35 used: dispersible 6 30-70 2.2 163OO micellarly Epoxyconazole: 6.63:10 g/100 ml (20° C.). dispersible Metconazole: 30.4 mg/l (20°C.). 7 20-80 2.5 16900 micellarly Pyraclostrobin: 1.9 mg/l (20° C.). dispersible 8 10-90 2.4 17800 micellarly The fungicidal effect of various formulations of the agro dispersible 40 chemical active ingredients epoxyconazole, metconazole and pyraclostrobin as a function of the concentration of applied Polydispersity index determined by means of gel permeation chromatography calculated as active ingredient was assessed in comparison with block PDI = M.M. copolymers and random polymer. B) Solubilization of Dyes from Solid Solution For this, one or more agrochemical active ingredient and B1) 45 the block copolymeras in Ex. 4 was mixed in the weight ratio A dye (Dianix Luminous Red, Dystar) and the polymeras active ingredient:polymer 1:2 and dissolved in DMF, and the in Ex. 4 were mixed in the weight ratio dye:polymer 33:67 solvent was then removed in a drying cabinet. The solid and dissolved in DMF, and the solvent was then removed in a solution obtained in this way was taken up with sufficient drying cabinet. The solid solution obtained in this way was water to give a 15% strength by weight polymer concentra taken up with sufficient water to give a 3% strength by weight 50 tion, based on the aqueous solution (corresponds to 30% by Solution, based on the polymer content, and filtered over a weight of active ingredient or active ingredient mixture, 0.45 um Millipore filter, and the dye content was determined based on the aqueous solution). For the application, the aque by means of HPLC/UV. Result: 10 mg/kg of dye dissolved in ous solution was further diluted with water so that a concen Water. tration of the aqueous solution of 0, 8, 16, 32, 64 or 100 ppm, For comparison, the polymer used was copovidone, a ran 55 based on the applied aqueous formulation, were obtained. dom copolymer of 60% by weight of VP and 40% by weight The determination of the damage picture was carried out on of VAc. Result: 2 mg/kg dye dissolved in water. The compari wheat of the Kanzler variety which had been infected before son shows that, in the presence of the block copolymer, five hand with the fungal species Puccinia recondita (experiments times more dye is solubilized than in the presence of a com F-0 to F-4). parable random copolymer not in accordance with the inven 60 For comparison, the process was repeated with the compa tion. rable VP-VAc copolymer 60/40 (copovidone, random B2) copolymer of 60% by weight VP and 40% by weight of VAc) Furthermore, solid solutions as described above were pre (comparative experiments C-0 to C-4). The control experi pared with the dye, block copolymer and, for comparison, ments K-1 to K-3 were carried out without active ingredient. with PVP homopolymers (PVP K90, K30, K17) and VP-VAc 65 The column "composition' shows the qualitative and copolymer 60/40 (copovidone) and dissolved in water, and quantitative composition of the particular copolymer with the solutions were assessed visually for color intensity. The which the active ingredient is present in the aqueous solution. US 8,211,469 B2 25 26 For all of the formulations, the weight ratio of polymer to was assessed after 1 hour with stirring with regard to the active ingredient was 2 to 1. The column “applied concentra formation of active ingredient crystals. For comparison, the tion' indicates in which concentration the active ingredient process was repeated with the comparable random VP-VAc formulations was applied. The column “plant appraisal” indi copolymer 60/40. cates, on a scale from 0 to 100, the remaining fungal attack 5 The following table (column "crystals observed') shows following treatment, where 100 means complete attack. The that, in the presence of the block copolymer, the active ingre stated value is a mean from three individual values. “n.a' dients do not crystallize out (experiments F-0 to F-4), means not applicable. whereas in the case of the corresponding active ingredient The control experiments without active ingredient have formulations with random copolymer (experiments C-0 to shown that the block copolymers exhibit low phytotoxicity, 10 C-4), crystals were observed. which is the same as or lower than in the case of comparable random copolymers. These comparative experiments show that, at the same Crystals active ingredient concentration, with the polyvinylactam No. Composition observed polyvinyl acetate block copolymers used according to the 15 K-1 Without active ingredient, Ila. invention as Solubilizers, considerably better agrochemical without polymer effects are to be achieved than in the presence of comparable K-2 VP-VAc (60:40), Ila. random polyvinylactam-polyvinyl acetate copolymers. This without active ingredient demonstrates the better bioavailability of the agrochemical K-3 Random VP-VAc (60:40), Ila. without active ingredient active ingredients by using the block copolymers as solubi F-0 VP-VAc (60:40) + No lizers. epoxyconazole F-1 VP-VAc (60:40) + No netconazole F-2 VP-VAc (60:40) + No Applied 25 metconazole epoxyconazole (3:2) concentration Plant F-3 VP-VAc (60:40) + No No. Composition ppm appraisal metconazole pyraclostrobin (2:3) F-4 VP-VAc (60:40) + No K-1 Without active ingredient, O 85 epoxyconazole? pyraclostrobin (5:7) without polymer C-O Random VP-VAc (60:40) + Yes k-2 VP-VAc (60:40), 100 8O 30 epoxyconazole without active ingredient C-1 Random VP-VAc (60:40) + Yes K-3 Random VP-VAc (60:40), 1OO 8O Inetconazole without active ingredient C-2 Random VP-VAc (60:40) + Yes F-O VP-VAc (60:40) + 6 O metconazole epoxyconazole (3:2) epoxyconazole 8 O C-3 Random VP-VAc (60:40) + Yes 4 5 35 metconazole pyraclostrobin (2:3) F-1 VP-VAc (60:40) + 32 O C-4 Random. VP-VAc (60:40) + Yes metconazole 6 4 epoxyconazole? pyraclostrobin (5:7) 8 4 F-2 VP-VAc (60:40) + 32 O metconazole epoxyconazole (3:2) 6 O 8 4 40 The invention claimed is: F-3 VP-VAc (60:40) + 64 O metconazole pyraclostrobin (2:3) 32 O 1. A composition comprising at least one agrochemical 6 8 active ingredient that is sparingly soluble in water, and at least F-4 VP-VAc (60:40) + 64 O one polyvinyllactam-polyvinyl acetate block copolymer, epoxyconazole pyraclostrobin 32 O wherein the at least one agrochemical active ingredient and (5:7) 6 6 45 C-O Random VP-VAc (60:40) + 6 9 the at least one polyvinyllactam-polyvinyl acetate block epoxyconazole 8 19 4 73 copolymer form a solid solution in which the at least one C-1 Random VP-VAc (60:40) + 32 17 agrochemical active ingredient is present in a molecularly metconazole 6 50 dispersed form in the solid polymer matrix, wherein said 8 65 block copolymer has an average molecular weight Mn of C-2 Random VP-VAc (60:40) + 32 1 50 metconazole epoxyconazole (3:2) 6 10 from 10,000 to 30,000 and wherein the molar ratio of poly 8 40 vinylactam to polyvinylacetate ranges from 30 to 70 to 70 to C-3 Random VP-VAc (60:40) + 64 15 30 wherein said polyvinylactam block is polyvinylpyrroli metconazole pyraclostrobin (2:3) 32 52 done. 6 75 C-4 Random. VP-VAc (60:40) + 64 12 55 2. The composition of claim 1, wherein said polyvinyllac epoxyconazole pyraclostrobin 32 43 tam-polyvinyl acetate block copolymer has an A-B, A-B-A or (5:7) 6 83 B-A-B structure. 3. The composition of claim 1, wherein said block copoly E) Crystallization Inhibitory Effect mer is water-soluble or water-dispersible. One or more agrochemical active ingredients (epoxycona 60 4. The composition of claim 1, wherein said agrochemical Zole, metconazole and/or pyraclostrobin) and the block active ingredients are selected from the group consisting of copolymeras in Ex. 4 were mixed in the weight ratio active epoxiconazole, metconazole, pyraclostrobin, kresoxim-me ingredient:polymer 1:2 and dissolved in DMF, and the sol thyl and 5-chloro-7-(4-methylpiperidin-1-yl)-6-(2,4,6-trif vent was then removed in a drying cabinet. The Solid Solution luorophenyl)-1.2.4 triazolo 1.5-alpyrimidine and boscalid. obtained in this way was taken up with sufficient water to 65 5. The composition of claim 1, wherein said agrochemical produce a 2% strength by weight solution, based on the poly active ingredients are a mixture of agrochemical active ingre mer content. Using a light microscope, the aqueous Solution dients comprising at least two different triazoles. US 8,211,469 B2 27 28 6. The composition of claim 5, wherein said mixture of 11. A method of Solubilizing said agrochemical active agrochemical active ingredients comprises at least one triaz ingredients of claim 1 comprising, mixing said agrochemical ole and at least one strobilurin. active ingredients, said polyvinylactum-polyvinyl acetate 7. The composition of claim 1, wherein the agrochemical block copolymer and water. 5 12. The method of claim 11, wherein at least 30 g of water active ingredient is selected from the group consisting of is required per g of said active ingredient(s) at 20° C. strobilurins, carboxamides, and azoles. 13. A method of controlling undesired insector mite attack 8. The composition of claim 1, wherein at least 10,000 on plants and/or for controlling phytopathogenic fungi, grams of water per gram of the agrochemical active ingredi wherein the fungi/insects, their habitat or the plants or ground ent is required to dissolve the agrochemical active ingredient. 10 to be protected against fungal or insect attack, or the plants, 9. The composition of claim 1, wherein the mass ratio of the ground on which the plants grow, or seeds thereof are the at least one polyvinylactam-polyvinyl acetate block treated with a composition of claim 1. copolymer to the agrochemical active ingredient ranges from 14. A method of controlling undesired plant growth, 1:2 (w/w) to 50:1 (w/w). wherein the undesired plants, the ground on which the undes 10. A method of preparing the composition of claim 1 15 ired plants grow, or seeds thereof are treated with a compo comprising, mixing said agrochemical active ingredients and sition of claim 1. said polyvinylactum-polyvinyl acetate block copolymer.