WO2010136125A1 - Powder formulas having adsorbent particles - Google Patents

Abstract

The present invention relates to powder formulas comprising active substances or particles comprising active substances, the release characteristics thereof being affected by adding particles adsorbing active substances, and a method for producing the powder formulas, and the use thereof.

Description

 Powder formulations with adsorbent particles

The present invention relates to powder formulations containing active substances or active substance-containing particles, the release characteristics of which are influenced by the addition of active substance adsorbing particles, and to processes for the preparation of the powder formulations and their use.

Especially in crop protection and horticulture such. In the case of seed dressing, the particularly long release of active substances with special release behavior, over weeks or months within a vegetation period, is of great interest.

Many active ingredients or drug formulations usually show a degressive release under release conditions. Thus, a time-decreasing release of the particular drug (e.g., a root function resulting from drug diffusion from a matrix or a exponentially decreasing first-order release).

The resulting initial disproportionate release is e.g. undesirable in plant protection in sensitive young plants. In applications such as e.g. the application of long-term releasing insecticides or fungicides in the seed treatment is desired to protect the seed, the seedling and the young plants dead time or a linear or even better a progressive release.

Another example where deadtime in release may be helpful is the control of gregarious insects. A dead time of the release makes it possible that the transporting insect initially takes no damage from the active ingredient in a formulation, but the active ingredient is released only in insects.

Different, general methods of coating active ingredient-containing particles are known from the prior art in order to set certain functions by means of a particle shell (eg dead time or defined release) (eg Mollet, Hans, Formulation Technology Emulsions, Suspensions, Solid Forms formulation technology, Weinheim Wiley). VCH 2001).

The disadvantage of conventional coatings to control the release is that often a trigger (temperature, aging, etc.) is required, which does not switch in the product life cycle for the desired release at the desired time or is difficult to comply until the use of the product , For example, often the temperature range of storage and ambient temperature overlap, if for a crop protection product, the temperature during the growing season should serve as a trigger. This aspect is particularly difficult to maintain a defined dead time. In addition, the processes for producing the required coating, in particular in the case of microscale particles, are often complicated (fluidized bed process, reactive coating, etc.).

The use of particles to which drugs adsorb is disclosed for drug formulations in WO 1996/38039 A1. Here, the use of activated carbon as a carrier substance is proposed, which is loaded with the drug. It is disclosed that the drug is molecularly adsorbed from a molecular solution thereof onto the surface of the activated carbon. It is further disclosed that the active compound is subsequently modified if necessary

Ambient conditions (pH value, active substance concentration of the surrounding phase, etc.) is released again.

The disclosure of WO 1996/38039 A1 is disadvantageous because in this procedure the active substance content of the formulation is limited by the fact that the maximum amount of active ingredient of the formulation is limited by the accessible free surface. It is therefore required by the limited adsorption capacity compared to the active ingredient, a large proportions of the activated carbon.

Mattern and Pieper (Powder Handling and Processing - 2004, Vol. 16, Iss. 2 - pp. 136-140) disclose the dry coating of activated carbon or starch as carrier with active ingredient particles to accelerate the release or taste masking of active ingredients. Activated carbon particles are used as the carrier material, not as coating particles for active ingredients, the coating of the carrier particles with active ingredient being carried out by a mechanical process according to the principle of a rotor impact mill in a cycle-batch mode (Nara hybridizer). The example of the active substance praziquantel describes a rapid initial release with taste masking, which is considered positive. Delayed initial release or dead time prior to initiation of release are not disclosed.

The influencing of the release of an active substance under release conditions with a first-order characteristic and thus a degressive release behavior in the direction of a zero-order release behavior is disclosed in WO 1992/019283 A1. The release is, however, influenced by a polymer membrane and not by the properties of active substance adsorbing particles.

The disclosure of WO 1992/019283 A1 is disadvantageous because the polymer membrane first has to be produced by spraying and two-stage removal of a solvent mixture by a comparatively complicated process. Furthermore, the method alone is significantly limited by the fact that the solvent mixtures used must be approved either for the use associated with the active ingredient used or must pass through an approval, or that must be ensured if an authorization is not possible that the solvents have been completely removed before using the formulation, which is complex and therefore economically disadvantageous.

Based on the prior art, the object is therefore to provide a powder formulation whose active substance release profile has a dead time or a weakened initial release and which does not have the disadvantages of the prior art. Another object is to provide a simple process for preparing this powder formulation.

Surprisingly, it has been discovered that a powder formulation comprising active ingredient or active ingredient-containing particles, which is characterized in that it comprises active substance adsorbing particles which contain no active ingredient, can achieve this object.

Active substance-containing particles in the context of the present invention are usually particles comprising at least one active substance which are either coated with a coating layer or particles which are combined in a matrix material into agglomerates or are applied to the matrix material. The matrix material may be a polymer or also an active substance adsorbing material, such as e.g. Be activated carbon. The cladding layer may be a polymeric or oligomeric material. The matrix material and / or the cladding layer are preferably a polymeric material.

Preferred polymeric materials are those from the list containing homopolymers with CC main chain bond, copolymers with CC main chain bond and with at least two different monomers, polyesters consisting of at least one aromatic dicarboxylic acid and one or more components from the group of aliphatic dihydric alcohols, polyamides, polyester amides, Polylactides, cellulose and its derivatives, starch and its derivatives, polyurethanes and polyketones.

If the polymeric materials are homopolymers with C-C main chain linkage, these are particularly preferably those selected from the list comprising polyethylene, polypropylene, polyvinyl chloride, polymethyl methacrylate, polyvinylpyrrolidone, polystyrene, polyacrylonitrile, polyvinyl acetate and acrylic acid.

If the polymeric materials are copolymers with CC main chain bond and with at least two different monomers, then the at least two different monomers, more preferably two or more of the substances selected from the list containing ethylene, propylene, styrene, vinyl chloride, vinyl acrylate, vinyl pyrollidone, acrylonitrile , Norbornene, acrylic acid, acrylamide, butadiene, isoprene, chloroprene and vinyl acetate. If the polymeric materials are polyesters comprising at least one aromatic dicarboxylic acid and one or more components from the group of the aliphatic dialcohols, the at least one aromatic dicarboxylic acid is particularly preferably terephthalic acid and / or isophthalic acid and the one or more components from the group of aliphatic dialcohols particularly preferably selected from the list containing diethylene glycol, butanediol, cyclohexane-1,4-dimethanol, 1-3 propanediol and hexanediol.

If the polymeric materials are polyamides, these are particularly preferably those selected from the list containing polyamide 6, polyamide 66, polyamide 4, polyamide 11 and polyamide 12.

If the polymeric materials are polyesteramides, the monomers of these polyesteramides are particularly preferably selected from the list containing ethylene glycol, butanediol, caprolactam, adipic acid, hexadimethylenediamine and terephthalic acid.

If the polymeric materials are cellulose and its derivatives, these are particularly preferably methylcellulose, hydroxypropylcellulose and / or cellulose acetate.

If the polymeric materials are starch and its derivatives, these are particularly preferably methyl starch, hydroxypropyl starch and / or starch acetate.

If the polymeric materials are polyurethanes, these are particularly preferably polyurethanes composed of polyfunctional isocyanates selected from the list containing diisocyanate-toluene, diphenylmethane-isocyanate, hexamethylene-diisocyanate and isophrone-diisocyanate with polyhydric alcohols selected from the list containing diethylene glycol, butanediol, cyclohexane. 1,4-dimethanol, 1-3 propanediol, hexanediol and glycerin.

The preferred and particularly preferred polymers are advantageous because, on the one hand, they can influence the release characteristics of the formulation without active substance adsorbing particles in the desired form; for example, they allow for a sufficiently long suspension of drug release and, secondly, they optionally have degradation products with sufficiently biocompatible properties (biological degradable or biocompatible polymers).

Preference is given to active ingredient-containing particles which are combined in a matrix material to form agglomerates or are applied to the matrix material.

Particularly preferred are active ingredient-containing particles which are combined in a polymeric matrix material into agglomerates or are applied to a polymeric matrix material.

The use of such active substance-containing particles is particularly advantageous because the polymeric matrix material forms a diffusion barrier by means of which the release rate can be adjusted. The active substance or active substance-containing particles according to the invention usually have a size of ds ₀ <1000 μm, preferably a size of d ₅₀ 10 to 500 μm, more preferably d ₅₀ 50 to 100 μm.

The active substances contained in the active substance or active substance-containing particles may belong to the fungicides, bactericides, insecticides, acaricides, nematicides, herbicides, plant growth regulators, plant nutrients or repellents.

If the active substances contained in the active ingredient or active substance particles are fungicides, these are preferably the substances selected from the list containing 2-anilino-4-methyl-6-cyclopropyl-pyrimidine; 2 ', 6'-dibromo-2-methyl-4'-trifluoromethoxy-4-trifluoromethyl-1,3-thiazole-5-carboxanilide; 2,6-Dichloro-N- (4-trifluoromethylbenzyl) benzamide; (E) -2-methoxymino-N-methyl-2- (2-phenoxyphenyl) -acetamide; 8-hydroxyquinoline sulfate; Methyl (E) -2- {2- [6- (2-cyanophenoxy) -pyrimidin-4-yloxy] -phenyl} -3-methoxyacrylate; Methyl (E) -methoximino [alpha- (o-tolyloxy) -o-divo; tolyl] -acetate; 2-phenylphenol (OPP), aldimorph, ampropylfos, anilazine, azaconazole, benalaxyl, benodanil, benomyl, binapacryl, biphenyl, bitertanol, blasticidin-S, bromuconazole, bupirimate, butiobate, calcium polysulfide, captafol, captan, carbendazim, carboxin,, carpropamide, Quinomethionate (quinomethionate), chloroneb, chloropierine, chlorothalonil, chlozolinate, cufraneb, cymoxanil, cyproconazole, cyprofuram, capropamide, dichlorophen, diclobutrazole, dichlofluanid, diclomethine, dicloran, diethofencarb, difenoconazole, dimethirimol, dimethomoφh, diniconazole, dinocap, diphenylamine, dipyrrithione, ditalimfos , Dithianon, Dodine, Drazoxolone, Edifenphos, Epoxyconazole, Ethirimol, Etridiazole, Fenamidone, Fenarimol, Fenbuconazole, Fenhexamid, Fenfuram, Fenitropan, Fenpiclonil, Fenpropidin, Fenpropimorph, Fentinacetate, Fentinhydroxide, Ferbam, Ferimzone, Fluazinam, Fludioxonil, Fluoromide, Fluoxastrobin, Fluquinconazole , Flusilazole, Flusulfamide, Flutolanil, Flutriafol, Folpet, Fosetyl-Aluminum, Fthalide, Fube ridazole, furalaxyl, furmecyclox, fenhexamide, guazatine, hexachlorobenzene, hexaconazole, hymexazole, imiazalil, imibenconazole, iminoctadine, iprophf (IBP), iprodione, isoprothiolane, iprovalicarb, kasugamycin, copper preparations such as: copper hydroxide, copper naphthenate, copper oxychloride, copper sulfate, copper oxide , Oxine-Copper and Bordeaux Blend, Mancopper, Mancozeb, Maneb, Mepanipyrim, Mepronil, Metalaxyl, Metconazole, Methasulfocarb, Methfuroxam, Metiram, Metominostrobin, Metsulfovax, Myclobutanil, Nickeldimethyldithiocarbamate, Nitrothal-isopropyl, Nuarimol, Ofurace, Oxadixyl, Oxamocarb, Oxycarboxin , Pefurazoate, penconazole, pencycuron, phosphodiphene, pimaricin, piperaline, polyoxin, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propyneb, prothioconazole, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, quintozene (PCNB), quinoxyfen, sulfur and sulfur preparations, Spiroxamine, tebuconazole, tecloftalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thiophanate-methyl, Thiram, tolclophos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, trichlamide, tricyclazole, tridemorph, Triflumizole, triforin, triticonazole, trifloxystrobin, validamycin A, vinclozoline, zineb, ziram, and 2- [2- (1-chloro-cyclopropyl) -3- (2-chlorophenyl) -2-hydroxypropyl] -2,4-dihydro- [l, 2,4] -triazole-3-thione.

If the active substances present in the active substance or active substance-containing particles are bactericides, these are preferably the substances selected from the list containing bronopol, dichlorophene, nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone, furancarboxylic acid, oxytetracycline, probenazole, streptomycin, tecloftalam, copper sulphate and other copper preparations.

If the active substances contained in the active substance or active substance particles are insecticides, acaricides or nematicides, these are preferably the substances selected from the list containing abamectin, acephate, acetamiprid, acrinathrin, alanycarb, aldicarb, alphamethrin, amitraz, avermectin, AZ 60541, Azadirachtin, Azinphos A, Azinphos M, Azocyclotin, Bacillus thuringiensis, 4-bromo-2- (4-chlorophenyl) -1- (ethoxymethyl) -5- (trifluoromethyl) -1H-pyrrole-3-carbonitriles, Bendiocarb, Benfuracarb, Bensultap , Betacyfluthrin, Bifenthrin, BPMC, Brofenprox, Bromophos A, Bufencarb, Buprofezin, Butocarboxine, Butylpyridaben, Cadusafos, Carbaryl, Carbofuran, Carbophenothione, Carbosulfan, Cartap, Chloethocarb, Chloretoxyfos, Chlorfenvinphos, Chlorfluazuron, Chlormephos, N - [(6-Chloro) 3-pyridinyl) -methyl] -N'-cyano-N-methyl-ethanimidamide, chloφyrifos, chloφyrifos M, cis-resmethrin, clocthrin, clofentezine, clothianidin, cyanophos, cycloprothrin, cyfluthrin, cyhalothrin, cyhexatin, cypermethrin, cyr omazine, deltamethrin, demeton-M, demeton-S, demeton-S-methyl, diafenthiuron, diazinon, dichlofenthione, dichlorvos, dicliphos, dicrotophos, diethione, diflubenzuron, dimethoate, dimethylvinphos, dioxathione, disulfoton, emamectin, esfenvalerate, ethiofenoc, ethion, Ethofenprox, Ethoprophos, Etrimphos, Fenamiphos, Fenazaquin, Fenbutatin Oxide, Fenitrothion, Fenobucarb, Fenothiocarb, Fenoxycarb, Fenpropathrin, Fenpyrad, Fenpyroximate, Fenthion, Fenvalerate, Fipronil, Fluazuron, Flucycloxuron, Flucythrinate, Flufenoxuron, Flufenprox, Fluvalinate, Fonophos, Formothion, Fosthiazate, Fubfenprox, Furathiocarb, HCH, Heptenophos, Hexaflumuron, Hexythiazox, Imidacloprid, Iprobenfos, Isazophos, Isofenphos, Isoprocarb, Isoxathione, Ivermectin, Lambda-cyhalothrin, Lufenuron, Malathion, Mecarbam, Mevinphos, Mesulfenphos, Metaldehyde, Methacrifos, Methamidophos, Methidathion, Methiocarb, Methomyl, Metolcarb, Milbemectin, Monocrotophos, Moxidectin, Naled, NC 184, Nitenpyram, Omethoate, Oxamyl, Oxydemethon M, Oxy deprofos, parathion A, parathion M, permethrin, phenthoate, phorate, phosalone, phosmet, phosphamidone, phoxim, pirimicarb, pirimiphos M, pirimiphos A, profenophos, promecarb, propaphos, propoxur, prothiophos, prothoate, pymetrozine, pyrachlophos, pyridaphenthione, pyresmethrin, Pyrethrum, Pyridaben, Pyrimidifen, Pyriproxifen, Quinalphos, Salithion, Sebufos, Silafluofen, Sulfotep, Sulprofos, Tebufenozide, Tebufenpyrad, Tebupirimiphos, Teflubenzuron, Tefluthrin, Temephos, Terbam, Terbufos, Tetrachlorvinphos, Thiacloprid, Thiafenox, thiamethoxam, thiodicarb, thiofanox, thiomethone, thionazine, thuringiensin, tralomethrin, transfluthrin, triarathene, triazophos, triazuron, trichlorofon, triflumuron, trimethacarb, vamidothion, XMC, xylylcarb, zetamethrin.

If the active substances contained in the active ingredient or active substance particles are herbicides, these are preferably the substances selected from the list containing anilides, such as. Diflufenican and propanil; Arylcarboxylic acids, such as e.g. Dichloro-picolinic acid, dicamba and picloram; Aryloxyalkanoic acids, e.g. 2,4-D, 2,4-DB, 2,4-DP, fluroxypyr, MCPA, MCPP and triclopyr; Aryloxyphenoxy-alkanoic acid esters, e.g. Diclofop-methyl, fenoxapropethyl, fluazifop-butyl, haloxyfop-methyl and quizalofop-ethyl; Azinones, such as Chloridazon and norflurazon; Carbamates, such as e.g. Chlorpropham, Desmedipham, Phenmedipham and Propham; Chloroacetanilides, e.g. Alachlor, acetochlor, butachlor, metazachlor, metolachlor, pretilachlor and propachlor; Dinitroanilines, e.g. Oryzalin, pendimethalin and trifluralin; Diphenyl ethers, e.g. Acifluorfen, bifenox, fluoroglycofen, fomesafen, halosafen, lactofen and oxyfluorfen; Ureas, such as e.g. Chlortoluron, diuron, fluometuron, isoproturon, linuron and methabenzthiazuron; Hydroxylamines, such as e.g. Alloxydim, clethodim, cycloxydim, sethoxydim and tralkoxydim; Imidazolinones, e.g. Imazethapyr, Imazamethabenz, Imazapyr and Imazaquin; Nitriles, e.g. Bromoxynil, dichlobenil and ioxynil; Oxyacetamides, e.g. mefenacet; Sulfonylureas, e.g. Amidosulfuron, bensulfuron-methyl, chlorimuronethyl, chlorosulfuron, cinosulfuron, metsulfuron-methyl, nicosulfuron, primisulfuron, pyrazosulfuron-ethyl, thifensulfuron-methyl, triasulfuron and tribenuron-methyl; Thiolcarbamates, e.g. Butylates, cycloates, dialkylates, EPTC, esprocarb, molinates, prosulfocarb, thiobencarb and triallates; Triazines, e.g. Atrazine, cyanazine, simazine, simetryne, terbutryne and terbutylazine; Triazinones, e.g. Hexazinone, metamitron and metribuzin; Others, e.g. Aminotriazole, benfuresates, bentazones, cinmethylin, clomazone, clopyralid, difenzoquat, dithiopyr, ethofumesates, fluorochloridones, glufosinates, glyphosates, isoxaben, pyridates, quinchlorac, quinmerac, sulphosates and tridiphanes. Also suitable are 4-amino-N- (1,1-dimethylethyl) -4,5-dihydro-3- (1-methylethyl) -5-oxo-1,2-H-1,2,4-triazole-1-carboxamide and benzoic acid -2 - ((((4,5-dihydro-4-methyl-5-oxo-3-propoxy-1 H-1, 2,4-triazol-1-yl) -carbonyl) -amino) -sulfonyl) - methyl ester.

If the active substances contained in the active ingredient or active substance particles are plant growth regulators, these are preferably chlorocholine chloride and / or ethephon.

If the active substances contained in the active ingredient or active substance particles are plant nutrients, these are preferably inorganic or organic fertilizers for supplying plants with macro and / or micronutrients. If the active substances contained in the active substance or active substance particles are repellents, these are preferably diethyl tolylamide, ethylhexanediol and / or butyrolactone.

Particularly preferred insecticides are the substances selected from the list containing imidacloprid, thiacloprid, thiamethoxam, acetamiprid, clothianidin, betacyfluthrin, cypermethrin, transfluthrin, lambda-cyhalothrin and azinphosmethyl.

Particularly preferred herbicides are the substances selected from the list containing propoxycarbazone sodium, flucarbazone sodium, amicarbazone and dichlobenil.

Particularly preferred fungicides are the substances selected from the list containing Bitertanol, Carbendazim, Carpropamid, Cyproconazole, Cyprofuram, Carpropamid, Edifenphos, Fenamidone, Fenhexamid, Fluoxastrobin, Fluquinconazole, Fosetyl-aluminum, Iprodione, Iprovalicarb, Metominostrobin, Pencycuron, Prochloraz, Propamocarb, Propineb , Prothioconazole, pyrimethanil, spiroxamine, tebuconazole, tolyfluanid, triadimefon, triadimenol, trifloxystrobin.

Active substance adsorbing particles in the context of the present invention are particles of a material which contains no active substance but can adsorb up to 50% by weight of active substance.

The active substance adsorbing particles usually have an average particle size d ₅₀ <1000 μm, preferably a size d ₅₀ of 10 to 500 μm, more preferably d ₅₀ 50 to 100 μm.

Preferred materials for the active substance adsorbing particles are non-toxic or non-harmful, particularly preferably inert and / or biodegradable or biocompatible substances.

Also preferred materials for the active substance adsorbing particles are water-insoluble or poorly water-soluble substances with a high specific surface area.

Such substances are particularly advantageous because the release of the active ingredients is often carried out in an aqueous environment or water-containing environment and not the material of the active substance adsorbing particles to be released, but the active ingredient of the active ingredient or drug-containing particles.

The preferred materials for the active substance adsorbing particles usually belong to the inorganic solids, as they are usually used as a catalyst support or alternatively for wastewater treatment.

Particularly preferred as materials for the active substance adsorbing particles are the substances selected from the list containing metal oxides, activated carbons, bentonite, bentonite sodium,

Bone meal, calcium carbonate, calcium octanoate, calcium oxide silicate, calcium sulfate, cellulose, Sea shells, ground coffee, diatomaceous earth, cottonseed meal, Douglas fir bark, egg shells, feldspar minerals, Walker earth, graphite, gypsum, hematite, potassium humic acid salt, humic acid sodium salt, iron magnesia, iron oxides, kaolin, limestone, magnesia, magnesium silicate, magnesium oxide silicate, magnesium siloxide, mica , Mica group minerals, montmorillonite, mullite, nepheline syenite, oysters, paper, paraffin wax, peat moss, perlite, stucco, polyethylene, pumice, rubber, sawdust, silica gel, silica, silicic acid, soap crust, tallow, wormstone, wollastonite, zeolites ( except erionite), zeolite Sodium A, zinc iron oxide, zinc oxide, polyacrylic acid, acrylate copolymers, aluminum hydroxide, aluminum octanoate, ashed sunflower seed husk, attapulgite, barium sulfate, boehmite, calcium phosphate, calcium zinc phosphate, cement, cetyloctanoate, charred bone meal, clay, cristobalite, dimethylsilicone polymer with silica, croscarmellose - Sodium, fishmeal, ground grass seeds, iron O-carbonate, iron hydroxide, magnesium hydroxide, manganese oxide, metakaolin, peanut meal, peanut shells, pecan shell meal, various metal phosphates, polyacrylamide polymers, polyamide, polypropylene, polystyrene, polyurethane, polyvinyl acetate, pyrophyllite, rosin polymers, Sand, dichlorodimethylsilane-modified silicas, silicone polymers, styrene-maleic anhydride copolymer, styrene-acrylic acid copolymer, styrene-divinylbenzene copolymer, styrene-acrylonitrile copolymer, various other copolymers, talc, titania, tridymite, urea-formaldehyde resin, vinyl acetate copolymers , Wheat flour, wood flour and zinc.

In the powder formulation according to the invention, the mean particle sizes d _{50 of} the active substance adsorbing particles are usually the same or smaller, preferably smaller by a factor of 2 than the active substance or active substance-containing particles, more preferably by a factor of 5 in the average diameter d ₅₀ smaller than the active substance or active ingredient-containing particles.

The powder formulation according to the invention usually contains from 0.01 to 99% by weight, preferably from 0.05 to 50% by weight, particularly preferably from 0.1 to 20% by weight, of active substance adsorbing particles.

The ranges given are advantageous in that selection of a higher level of drug adsorbing particles allows for greater attenuation of the initial release, or even a dead time for several hours to days, while the selection of a lower level results in higher later release. In principle, the powder formulation according to the invention is therefore limited only to the extent that it must comprise at least one proportion of active substance adsorbing particles and at least one proportion of active substance-containing particles in the powder formulation. The preferred and particularly preferred ranges of the proportions according to the present invention are particularly advantageous because they have an increased proportion of active ingredient resulting in a later increased compared to the previously known powder formulations release to achieve a weakening the initial release and possibly even reaching a dead time, without the need for a trigger can achieve.

The erfϊndungsgemäße powder formulation may also comprise fillers and / or additives in an alternative embodiment.

If the powder formulation according to the invention comprises fillers, the fillers may be organic or mineral fillers.

If the powder formulation according to the invention comprises mineral fillers, the mineral fillers are preferably oxides and / or hydroxides, carbonates and sulfates of calcium, silicates, glass structures and / or quartz sand.

Non-limiting examples of such preferred mineral fillers are zinc oxide, magnesium hydroxide, aluminum hydroxide, chalk, gypsum, bentonite, kaolin, talc, phlogopite, zeolites, mica, silicas, glass fibers, glass beads or glass flour.

If the powder formulation according to the invention comprises organic fillers, the organic fillers are preferably carbon structures, celluose and its derivatives, acrylic acid and its derivatives and / or xanthan.

Non-exhaustive examples of preferred organic fillers in the form of carbon structures are activated carbon, carbon black or carbon nanotubes.

If the powder formulation according to the invention comprises additives, the additives may be of organic or inorganic nature. Commonly included additives are then the additives selected from the list containing wetting agents, dispersants, emulsifiers, lubricants, lubricants, defoamers, stabilizers, preservatives, antifreezes, antioxidants and dyes.

The sum of the proportions of additives and fillers in the powder formulation according to the invention, when contained in the powder formulation, is from 0 to 50% by weight, preferably in the range from 0 to 30% by weight and more preferably in the range from 0 to 10% by weight.

In a preferred development of the invention, the powder formulations are characterized in that the active substance or active substance-containing particles and the active substance-adsorbing particles are fixed to one another.

In the context of the present invention, fixed to one another means that adhesive forces act between the particles. The adhesive forces are usually electrostatic forces and / or van der Waals forces, adhesive forces and / or forces by positive and / or non-positive connection of the particles.

The electrostatic forces arise in an advantageous manner by the disclosed materials from which the active substance adsorbing particles may consist and / or contained by the disclosed materials in the active ingredient-containing particles and / or by the active ingredient particles themselves.

It is essential for this that the active substance adsorbing particles and the active substance-containing particles and / or active substance particles have a surface which prevents the discharge of an electric charge as possible. This is achieved, for example, by the use of the above-mentioned, preferred active ingredient-containing particles which comprise a polymeric matrix material and / or such a coating layer, since polymers generally can only poorly derive electrical charges.

The van der Waals forces arise in an advantageous manner by the disclosed particle sizes of active ingredient-containing particles and / or active substance adsorbing particles in the abovementioned limits according to the invention. In particular, the ratios of the specified average particle sizes d ₅₀ lead here to particularly advantageous effects on the expression of van der Waals forces and thus to the desired release properties, as well as the other advantageous properties of the powder formulation, which will be described later.

The adhesive forces are advantageously produced by adhesives and / or adhesion promoters located between the particles. Non-limiting examples of adhesives and / or adhesion promoters are polyvinyl pyrrolidones, polyvinyl acetates, polyvinyl alcohols and cellulose ethers.

The forces by positive and / or non-positive connection of the particles are usually achieved by mechanical introduction of the active substance adsorbing particles into the surface of the active substance-containing particles according to the inventive method.

Combinations of these forces are also possible.

In an alternative embodiment of the preferred further development, the active substance or active substance-containing particles and the active substance-adsorbing particles are fixed to one another by the particles being present in a matrix. The matrix may consist of the materials that have already been disclosed as possible materials for the active ingredient-containing particles or may be an adhesive and / or adhesion promoter. The preferred development of the invention is particularly advantageous because the segregation, ie the separation of active ingredient or active substance-containing particles of active substance adsorbing particles of the powder formulation during storage and transport can be achieved by fixing the particles to one another with a possibly unequal distribution Particles in the powder formulation in use can be avoided.

The disclosed powder formulations comprising active substance-adsorbing particles are furthermore particularly advantageous because they can bring about a weakening of the release or even a dead time over several hours to days.

Another object of the invention is a process for preparing the powder formulations according to the invention and their preferred embodiments and further developments, characterized in that the active substance adsorbing particles are fixed to the active substance or active substance-containing particles.

Fixing is usually carried out by mixing the active substance adsorbing particles with the active substance or active substance-containing particles.

The mixing of the active substance or active substance-containing particles with the active substance-adsorbing particles can be carried out by conventional mixing methods of mechanical process engineering. Such conventional mixing methods can be carried out continuously or discontinuously.

Non-exhaustive examples of devices in which such mixing can be carried out are one-, two- or three-dimensional free fall mixers, single or multiple shaft mixers with rotating internals, pneumatic mixers, or other mixers known in mechanical engineering or more intensive intensive systems Dispersing and mixing action.

Special embodiments of one-, two- or three-dimensional free-fall mixers are, for example, silo mixers, Röhnrad mixers, double cone mixers, container mixers, trouser mixers or Turbula mixers.

Special embodiments of single or multi-shaft mixers are, for example, plowshare mixers, multi-flow fluid mixers, vertical mixers in single or twin-shaft operation or Eirich mixers.

Special embodiments of other mixers known in mechanical process engineering or alternative systems with intensive dispersing and mixing action are, for example, rotor impact mills, jet mills or Mahlköpermühlen. In the embodiment of the invention, the fixing is carried out by a simple mixing, wherein the average particle sizes d _{50 of} the active ingredient or drug-containing particles and the active substance adsorbing particles, and preferably the particle size ratios are maintained according to the powder formulation of the invention.

This procedure is particularly advantageous because van der Waals forces essentially ensure the adhesive forces between the active substance or active substance-containing particles and the active substance-adsorbing particles, and thus the powder formulation according to the invention can be obtained in a simple manner.

In a further development of the method according to the invention, the fixing is carried out by mixing and additional strong mechanical stressing of the particles.

This further development is particularly advantageous because in this way the adhesive forces between the active substance or active substance-containing particles and the active substance-adsorbing particles can additionally be achieved by positive and / or frictional connection of same.

Possible special embodiments for strong mechanical stressing of the particles are the setting of high particle wall impact velocities, for example by appropriate adjustment of the devices in the described conventional mixing methods of mechanical processing technology.

In an alternative embodiment of the method according to the invention, the fixing of the active substance adsorbing particles to the active substance or active substance-containing particles is achieved by incorporating the particles in a matrix.

The matrix materials which can be used herein are those of the alternative embodiment of the preferred development of the powder formulation of the invention.

Incorporation according to the alternative embodiment of the process is usually carried out by well-known melt / solids compounding or granulation processes.

Typical embodiments of devices for carrying out the melt / solid compounding processes are, for example, extruders or kneaders.

Preferred kneaders in which the process is carried out are Sigma kneaders, Vierwellenkneter and / or single-shaft Ko-kneader. Preferred extruders in which the process is carried out are single-screw extruders, single-shaft oscillating extruders, co-rotating or counterrotating twin-screw extruders, multi-screw extruders and / or planetary extruders.

If the incorporation is carried out in the form of a granulation, this can be done by granulation from a suspension of the particles, by a press granulation, build-up granulation or wet solid form.

Non-exhaustive examples of such process variants are in each case spray drying / fluidized bed granulation, roll compaction, plate granulation or pellet pressing.

The powder formulations obtained according to the invention and from the alternative embodiment of the process comprise particles which usually have an average particle size of d ₅₀ <1000 μm, preferably d ₅₀ <500 μm, particularly preferably d ₅₀ <100 μm.

The alternative embodiments of the preferred further development of the powder formulation according to the invention produced by the alternative embodiment of the method according to the invention are particularly advantageous because a change in the release characteristics is possible by separately setting several independent properties of the powder formulation during the process.

If a high proportion of matrix material is used in the process, the water entering the powder formulation can advantageously dissolve the active ingredient and / or optionally whole active substance particles from the matrix material, while the active ingredient or the active ingredient particles repeats several times until released from the powder formulation the surfaces of the active substance adsorbing particles in the matrix material come into contact, so that first, as desired, no or only a greatly attenuated release is achieved.

Irrespective of the dead time, if any, a change in the subsequent release can be effected in a simple and advantageous manner by the material and amount of the active substance adsorbing particles, by the composition of the active substance - containing particles in the powder formulation and by the process parameters in the preparation of the mixture or of the fixed mixture or further solid formulation.

A final object of the present invention is the use of the powder formulations according to the invention for seed treatment, in the form of long-term releasing insecticides, herbicides or fungicides, as well as for controlling gregarious living insects. The invention is explained in more detail below with reference to figures and examples, without limiting it thereto.

FIG. 1 shows a release profile of the powder formulations according to the invention from Example 2 with active-substance adsorbing particles of activated carbon.

FIG. 2 shows a release profile of the powder formulations of Example 1 according to the invention with coating by different types of active substance adsorbing particles.

FIG. 3 shows a release profile of the powder formulations from Example 1 with coating by further different types of active substance adsorbing particles.

FIG. 4 shows an SEM uptake of an active-carbon-coated active substance-containing particle with matrix material as in Example 1.

FIG. 5 shows a CLSM image of an embedding of activated carbon-coated particles as in Example 1. Numeral: 1- core particle / polymer drug matrix; 2- shell particles / adsorbent particles shown.

FIG. 6 shows a release profile of the powder formulations of Example 1 after 4 months storage time.

Examples:

Example 1 Production of a Core-Shell Formulation with Polymer-Active-Matrix-Particles as Core and Activated Carbon as Adsorbent Shell Particles by Mechanical Fixation.

An extrusion compound consisting of 30% imidacloprid, 65% SAN (styrene-acrylonitrile) and 5% kaolin was comminuted by cold grinding (mill with pre-cooled nitrogen as grinding gas) to a mean particle size ds ₀ of about 60 microns.

100 g of a premix of 99% of the extrusion compound (= core particle) and 1% of a finely particulate activated carbon (= adsorbent particle) were used in a cycle-operated, inertizable and coolable device based on the principle of a rotor impact mill (type Nara Hybridizer NHS-I). with a d ₅₀ of about 20 microns (type: Fa. Norit, A Supra EUR), 3 minutes at 8000 rev / min claimed.

Likewise, further fixed mixtures were prepared with 0.5%, 2% and 5% activated carbon of the same type (concentration of adsorbent particles in each case based on the entire formulation). In addition, fixed mixtures with further activated carbon types (type Norit, SX Ultra CAT, type Norit E Spec E 153) of alternative specifications with regard to particle sizes of specific surfaces, adsorption capacity, etc. were prepared, each with 1% adsorbent content based on the entire mixture.

The release profiles of the prepared particles were characterized according to the following method:

Depending on the active ingredient content, a quantity of sample is weighed into a 100 ml glass bottle and treated with deionised water to give a concentration of about 1000 ppm of active ingredient. The bottles are stored on a horizontal shaker (DCA) and shaken and homogenised at a frequency of 150 l / s. The sampling takes place at different time intervals. For this purpose, a 2 ml sample was taken with the aid of a disposable syringe and filtered through a 0.20 μm syringe filter (Sartorius MINISART) into an HPLC vial.

Sampling and HPLC analysis as a function of time gives the release profile.

The release depending on the amount of the adsorbent particles is shown in Fig. 1, the release depending on the adsorbent particle type is shown in Fig. 2.

The morphology of the core-shell formulation of polymer-drug-matrix particles as core and adsorbent particles as mechanically applied shell particles are visualized in FIGS. 4 and 5. Example 2: Preparation of a Simple, Non-Fused Mixture of Activated Carbon as Adsorbent Particles and Polymer-Active-Matrix Particles

To produce a simple, unfixed mixture, a defined amount (about 10 g) of particles of the extruded and ground compound from Example 1 as core particles with 0.5%, 1% and 2% activated carbon (type: Fa. Norit, A Supra EUR) as adsorbent particles (concentration of the adsorbent particles in each case based on the mixture) mixed in a sample bottle by manual shaking according to a free-fall mixture.

Subsequently, the release was measured by the method described in Example 1 (see Fig. 3).

Example 3: Design of the release profile of the formulation of Example 1 after 4 months storage time

In order to investigate whether the release behavior of the formulation according to the invention changes when stored dry at room temperature, the release profiles of the formulations from Example 1 were measured after 4 months storage time.

The release behavior in FIG. 6 shows that the dead time and the amounts of active substance released are similar after the dead time of the release profile has been exceeded with and without storage time and thus no relevant changes in the release profile have been observed in the application by storage under the selected storage conditions (dry, room temperature) ,

Claims

Claims: 1. Powder formulation comprising active ingredient or active ingredient-containing particles, which is characterized in that it comprises active substance adsorbing particles which contain no active ingredient. 2. Powder formulation according to claim 1, characterized in that the middle Particle sizes d _{50 of} the active substance adsorbing particles are equal to or smaller, preferably smaller by a factor of 2 than the active substance or active substance-containing particles, particularly preferably by a factor of 5 in the average diameter d _50, than the active substance or active substance-containing particles. 3. Powder formulation according to claim 1 or 2, characterized in that active ingredient or active ingredient-containing particles are either coated with a coating layer or are combined in a matrix material to form agglomerates or applied to the matrix material. 4. Powder formulation according to claim 3, characterized in that the matrix material is a polymer or an active substance adsorbing material. 5. Powder formulation according to claim 4, characterized in that the active substance adsorbing material is activated carbon. 6. Powder formulation according to claim 3, characterized in that the coating layer is a polymer. 7. Powder formulation according to claim 4 or 6, characterized in that the Polymer is a substance selected from the list consisting of homopolymers having CC main chain linkage, copolymers having CC main chain linkage and having at least two different monomers, polyesters comprising at least one aromatic dicarboxylic acid and one or more components from the group of aliphatic dialcohols, polyamides, polyester amides, Polylactides, cellulose and its derivatives, starch and its derivatives, polyurethanes and polyketones. 8. A process for the preparation of a powder formulation, characterized in that drug-adsorbing particles are fixed to drug or drug-containing particles.