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EP1571906A2 - Formulations pulverulentes de principes actifs - Google Patents

Formulations pulverulentes de principes actifs

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Publication number
EP1571906A2
EP1571906A2 EP02774722A EP02774722A EP1571906A2 EP 1571906 A2 EP1571906 A2 EP 1571906A2 EP 02774722 A EP02774722 A EP 02774722A EP 02774722 A EP02774722 A EP 02774722A EP 1571906 A2 EP1571906 A2 EP 1571906A2
Authority
EP
European Patent Office
Prior art keywords
active ingredient
polyvinyl alcohol
active
active substance
substances
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP02774722A
Other languages
German (de)
English (en)
Inventor
Karl Reizlein
Bernd Klinksiek
Jürgen Hinderer
Peter Baur
Anne Suty-Heinze
Astrid Mauler-Machnik
Heike Bunjes
Kirsten Westesen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer CropScience AG
Original Assignee
Bayer CropScience AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer CropScience AG filed Critical Bayer CropScience AG
Publication of EP1571906A2 publication Critical patent/EP1571906A2/fr
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/12—Powders or granules
    • A01N25/14—Powders or granules wettable
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/26—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests in coated particulate form
    • A01N25/28—Microcapsules or nanocapsules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Definitions

  • the present invention relates to new powdered active ingredient formulations, a process for their preparation and their use for applying the biologically active active ingredients contained.
  • WO 94-20 072 and US Pat. No. 5,785,976 describe suspensions of solid active substances which are sparingly soluble in water.
  • These formulations can be prepared by melting solid active ingredient, heating the dispersion medium to about the temperature of the active ingredient melt, adding a water-soluble stabilizer to the dispersion medium and optionally adding a lipid-soluble stabilizer to the active ingredient melt, then melt and dispersion are mixed and homogenized and the dispersion obtained is cooled.
  • the effectiveness of these formulations when freshly prepared is good.
  • WO 95-05 164 discloses formulations of substances which are sparingly soluble in water in the form of supercooled melts, in which the substances are liquid, are at least partially in an amorphous state and have diameters in the nanometer range.
  • these preparations are of limited stability due to the partially crystalline state, since recrystallization can occur.
  • solid plant treatment agents are known from WO 98-16 105 in which the active ingredients are very finely divided, essentially in amorphous form and are surrounded by a polymeric coating. These preparations are obtained by mixing a liquid formulation of the active ingredient with a liquid formulation of the coating material and from the resulting formulation. Mix the solvent away.
  • the stability and the effectiveness of the formulations obtained are not always sufficient.
  • the procedure is quite complex because both solvents and significant amounts of water have to be removed.
  • At least one active ingredient that is solid at room temperature at least one dispersant, polyvinyl alcohol and optionally additives
  • the individual active ingredient particles being encased in a layer of polyvinyl alcohol, in an amorphous state and having diameters in the nanometer range.
  • powdered active substance formulations according to the invention can be prepared by:
  • the resulting suspension is heated up to such an extent that the solid components it contains melt, c) the resulting dispersion is first homogenized and then rapidly cooled to a temperature below the solidification point of the dispersed components,
  • Formulations are very suitable for application of the active ingredients contained.
  • the powdered active substance formulations according to the invention are considerably more stable than the structurally most similar, known preparations which are accessible by melt dispersion, but in which the individual particles are not encapsulated.
  • the stability of the formulations according to the invention is also unexpected because it can be assumed that the polyvinyl alcohol layer dissolves when the powders are stirred with water and there was therefore a fear that the unprotected, amorphous active ingredient would recrystallize. Contrary to expectations, this effect does not occur.
  • the powdered active substance preparations according to the invention are also notable for a number of advantages.
  • the proportion of active substance is very high compared to corresponding previously known formulations. This means that even a small amount of formulation is sufficient to apply the desired amount of active component.
  • the powdered active substance formulations according to the invention can be redispersed without problems before use and the bioavailability of the active components is maintained at the high level achieved after production.
  • it is favorable that the thermal load on the active ingredients during the preparation of the formulations is relatively low.
  • neither additional carrier materials nor organic solvents are required for the production of the powder formulations according to the invention. Otherwise, those active ingredients whose melting point is well above 100 ° C. can also be processed without problems using the process according to the invention.
  • Active substances which are contained in the powdered formulations according to the invention are pharmaceutical active substances, agrochemical active substances and flavors which are solid at room temperature.
  • active pharmaceutical ingredients examples include ibuprofen, clotrimazole, fluconazole, indoxacarb and ciprofioxazin.
  • fungicides are:
  • Chloroneb chloropicrin, chlorothalonil, chlozolinate, cufraneb, cymoxanil, cy-proconazole, cyprofuram, carpropamide,
  • Mancopper Mancozeb, Maneb, Mepampyrim, Mepronil, Metalaxyl, Metconazol,
  • Tebuconazole Tebuconazole, tecloftalam, tecnazen, thiabendazole, thicyofen, thiophanate-methyl
  • bactericides are:
  • insecticides examples include acaricides and nematicides.
  • Phos pymetrozine pyridaphenthion, Pyresmethrin, pyridaben, pyrimidifen, pyriproxyfen, quinalphos, salithion, Sebufos, tebufenozide, tebufenpyrad, Tebupirimiphos, teflubenzuron, tefluthrin, Teme-, terbam.
  • Tetrachlorvinphos Tetrachlorvinphos, Thiacloprid, Thiafenox, Thiamethoxam, Thiodicarb, Thiofanox, Thiomethon, Thuringiensin, Tralomethrin, Transfluthrin, Triarathen, Triazuron, Trichlorfon, Triflumuron, Trimethacarb, Vamidothionet, XMC, XMC, XMC.
  • molluscicides are metaldehyde and methiocarb.
  • herbicides examples are:
  • Anilides such as diflufenican and propanil; Aryl carboxylic acids such as dichloropicolinic acid, dicamba and picloram; Aryloxyalkanoic acids such as 2,4-D, 2,4-DB, 2,4-DP, fluroxypyr, MCPA, MCPP and triclopyr; Aryloxy-phenoxy-alkanoic acid esters, such as, for example, diclofop-methyl, fenoxaprop-ethyl, haloxyfop-methyl and quizalofop-ethyl; Azinones such as chloridazon and norflurazon; Carbamates such as chlorpropham, desmedipham, phenmedipham and propham; Chloroacetanilides such as alachlor, metazachlor and propachlor; Dinitroanilines such as oryzalin, pendimethalin and trifluralin; Diphenyl ethers, such as, for example, acifluorfen, bifenox
  • Triazinones e.g. Hexazinone, metamitron and metribuzin
  • Others such as Aminotriazole, Benfuresate, Bentazone, Clomazone, Clopyralid, Difenzoquat, Dithiopyr, Etho colmesate, Fluorochloridone, Glufosinate, Glyphosate, Isoxaben, Pyridate, Quinchlorac, Quinmerac, Sulphosate and Tridiphane.
  • Chlorcholine chloride and ethephon are examples of plant growth regulators.
  • suitable dispersants are all customary nonionic, anionic, cationic and zwitterionic substances with the desired surface-active properties, which are usually used in such preparations. These substances also include reaction products of fatty acids, fatty acid esters, fatty alcohols, fertamines, alkylphenols or alkylarylphenols with ethylene oxide and / or propylene oxide, and also their sulfuric acid esters, phosphoric acid monoesters and phosphoric acid di-esters, as well as reaction products of ethylene oxide with propylene oxide Alkyl sulfonates, alkyl sulfates, aryl sulfates, tetra-alkyl ammonium halides, trialkylaryl ammonium halides and alkyl amine sulfonates.
  • the dispersants can be used individually or in a mixture. Reaction products of castor oil with ethylene oxide in a molar ratio of 1:20 to 1:60, reaction products of C6-C20 alcohols with ethylene oxide in a molar ratio of 1: 5 to 1:50, reaction products products of fatty amines with ethylene oxide in a molar ratio of 1: 2 to 1:20, reaction products of 1 mol of phenol with 2 to 3 mols of styrene and 10 to 50 mols of ethylene oxide, reaction products of C 8 -C 12 alkylphenols with ethylene oxide in a molar ratio of 1: 5 to 1:30, alkyl polyglycosides, C 8 -C 16 alkylbenzene sulfonic acid salts, such as calcium, monoethanolammonium, diethanolammonium and triethanolammonium salts.
  • nonionic dispersants are the products known under the names Pluronic PE 10 100 and Pluronic F 68 (from BASF) and Atlox 4913 (from Uniqema). Tristyrylphenyl ethoxylates are also suitable.
  • dispersants which may also be mentioned are copolymers of ethylene oxide and propylene oxide, reaction products of tristyrylphenol with ethylene oxide and / or propylene oxide, such as tristyrylphenol ethoxylate with an average of 24 ethylene oxide groups, tristyrylphenol ethoxylate with an average of 54 ethylene oxide groups.
  • tristyrylphenol ethoxylate propoxylate with an average of 6 ethylene oxide and 8 propylene oxide groups furthermore phosphated or sulfated tristyrylphenol ethoxylates, such as phosphated tristyrylphenol ethoxylate with an average of 16 ethylene oxide groups, sulfated tristyrylphenol ethoxylate with an average of 16 ethylene oxide -Groups or ammonium salt of phosphated
  • Tristyrylphenol ethoxylate with an average of 16 ethylene oxide groups also phospholipids, such as lecithin, optionally in a mixture with bile salts, such as sodium glucocholate, and also liguinsulfonates.
  • substances with wetting properties are also suitable.
  • polyvinyl alcohol means both water-soluble polymerization products of vinyl alcohol and water-soluble, partially saponified polymers of vinyl acetate. Polyvinyl alcohol with an average molecular weight between 10,000 and 200,000 is preferred.
  • Clariant product known under the trade name Mowiol® 3-83.
  • partially saponified polyvinyl acetate with an average molecular weight between 13,000 and 130,000 and an acetate group content between 1 and 28%.
  • polyvinyl alcohols obtained by partial saponification of polyvinyl acetate with a degree of hydrolysis of 72 to 99 mol% and a viscosity of 2 to 40 mPa.s, particularly preferably between 3 and 18 mPa.s, measured on a 4% -like, aqueous solution at 20 ° C. Both individual partially saponified polyvinyl acetates and mixtures can be considered.
  • Suitable additives that can be contained in the formulations according to the invention are penetration promoters, defoamers, cold stabilizers, preservatives, dyes, redispersants, disintegrants, inert fillers and film-forming substances.
  • penetration promoters are all those substances which are usually used to prevent the penetration of to improve agrochemical active substances in plants.
  • Alkanol alkoxylates of the formula are preferred
  • R represents straight-chain or branched alkyl having 4 to 20 carbon atoms
  • AO stands for an ethylene oxide residue, a propylene oxide residue, a butylene oxide residue or for mixtures of ethylene oxide and propylene oxide residues and
  • n stands for numbers from 2 to 30.
  • a particularly preferred group of penetration promoters are alkanol alkoxylates of the formula
  • R has the meaning given above, EO stands for -CH 2 -CH 2 -O- and n stands for numbers from 2 to 20.
  • Another particularly preferred group of penetration promoters are alkanol alkoxylates of the formula
  • EO stands for -CH 2 -CH 2 -O-
  • CH 3 p stands for numbers from 1 to 10
  • Another particularly preferred group of penetration promoters are alkanol alkoxylates of the formula
  • EO stands for -CH 2 -CH 2 -O-, 0
  • CH 3 r stands for numbers from 1 to 10
  • Another particularly preferred group of penetration promoters are alkanol alkoxylates of the formula CH 3 - (CH 2 ) t -CH 2 -O - (- CH 2 -CH 2 -O-) u -H (Id) in which
  • u stands for numbers from 6 to 17.
  • R preferably for butyl, i-butyl, n-pentyl, i-pentyl, neopentyl, n-hexyl, i-hexyl, n-octyl, i-octyl, 2-ethyl-hexyl, nonyl, i-nonyl, decyl, n -Dodecyl, i-dodecyl, lauryl, myristyl, i-tridecyl, trimethyl-nonyl, palmityl, stearyl or eicosyl.
  • alkanol alkoxylate of the formula (Ic) is 2-ethylhexyl alkoxylate of the formula
  • EO stands for -CH 2 -CH 2 -O-
  • u stands for numbers from 7 to 9.
  • alkanol alkoxylates are generally defined by the above formulas. These substances are mixtures of substances of the specified type with different chain lengths. Average values are therefore calculated for the indices, which can also deviate from whole numbers.
  • Examples include alkanol alkoxylate of the formula (Id), in which
  • u stands for the average value 8.4.
  • alkanol alkoxylates of the formulas given are known or can be prepared by known methods (cf. WO 98-35 553, WO 00-35 278 and EP-A
  • Defoamers are all substances which can normally be used for this purpose in agrochemical compositions. Silicone oils and magnesium stearate are preferred.
  • Cold stabilizers are all commonly used for. this purpose in agrochemical ⁇ mix means substances in question. Examples include urea, glycerin and propylene glycol. All substances that can normally be used for this purpose in agrochemical compositions of this type are suitable as preservatives. Examples include Preventol® (Bayer AG) and Proxel®.
  • Suitable redispersants are all substances which can normally be used for this purpose in solid agrochemical compositions.
  • Preferred surfactants are
  • Lactose, urea, polyethylene glycol and tetramethylolpropane may be mentioned as examples.
  • Suitable so-called disintegrants are substances which are suitable for accelerating the disintegration of the powder formulations according to the invention when mixed with water. Salts such as sodium chloride and potassium chloride are preferred.
  • Suitable inert filling materials are all substances which can normally be used for this purpose in agrochemical compositions.
  • Inorganic particles such as carbonates, silicates and oxides, and also organic substances, such as, are preferred
  • Urea-formaldehyde condensates examples include kaolin, rutile, silicon dioxide, so-called highly disperse silica, silica gels and natural and synthetic silicates, and talc.
  • water-soluble substances usually used for this purpose in active substance formulations come into question.
  • Gelatin water-soluble starch and water-soluble copolymers of polyvinyl alcohol and polyvinylpyrrolidone are preferred.
  • the content of the individual components can be varied within a substantial range in the powdered active ingredient formulations according to the invention. So the concentrations are
  • solid active substances generally between 10 and 50% by weight, preferably between 15 and 40% by weight,
  • dispersant in general between . 5 and 50% by weight, preferably between 7.5 and 40% by weight,
  • polyvinyl alcohol generally between 10 and 30 wt .-%, preferably between 15 and 30 wt .-% and
  • additives generally between 0 and 50 wt .-%, preferably between 0 and 40 wt .-%.
  • the powdered active ingredient formulations according to the invention contain active ingredient particles, each of which is surrounded by a polyvinyl alcohol shell, and consist of individual particles, each of which is surrounded by a polyvinyl alcohol matrix.
  • the shell-forming polyvinyl alcohol can also contain other water-soluble, film-forming substances.
  • the particles are in the amorphous state and have an average diameter in the nanometer range.
  • step (a) is carried out in such a way that finely divided, optionally pre-ground active ingredient and dispersant and, if appropriate, additives are suspended in water with stirring. It is generally carried out at temperatures between 10 ° C and 30 ° C, preferably at room temperature.
  • the resulting suspension is heated in the following step (b) of the process according to the invention in such a way that the solid components used melt and an emulsion is formed in which the melt is distributed in droplets in the water phase.
  • the process is carried out at temperatures above the melting point of the respective active ingredient, generally at temperatures between 40 ° C. and 220 ° C., preferably between 50 ° C. and 220 ° C.
  • the heating is preferably carried out quickly, so that an emulsion is only present for a short time.
  • the homogenization in the jet disperser which is also referred to as melt dispersion, generally takes place at temperatures between 40 ° C. and 220 ° C., but in any case above the melting point of the solid used
  • the subsequent cooling takes place to a temperature below the melting point of the solid components, so that a very fine dispersion of solidified droplets is formed in the water phase. In some cases, however, it is also possible to generate emulsions by cooling to temperatures above the fixed point of the melt.
  • melt dispersion When the melt dispersion is carried out, it is generally carried out under elevated pressure, preferably between 50 bar and 1,600 bar, particularly preferably between 60 bar and 1,000 bar.
  • step (d) of the process according to the invention the very finely divided dispersion in which the previously present droplets are generally solidified is encapsulated with an aqueous solution of polyvinyl alcohol, optionally in a mixture with other coating materials, and optionally with additives and the resulting mixture is then subjected to spray drying.
  • the addition of the aqueous solution in step (d) is generally carried out at temperatures between 10 ° C. and 50 ° C., preferably between 20 ° C. and 40 ° C. In spray drying, the temperatures can be varied within a wide range. In general, air inlet temperatures between 100 ° C. and 200 ° C., preferably between 120 ° C. and 180 ° C., and air outlet temperatures between 50 ° C. and 100 ° C., preferably between 60 ° C. and 90 ° C.
  • step (d) Both spray drying and freeze drying work in such a way that only a very low residual moisture remains in the powder formulation. In general, drying is carried out to such an extent that the residual moisture is below 1%. If aqueous polyvinyl alcohol solution is already added as an additive in carrying out the process according to the invention in step (a), the addition of this capsule-forming shell material in step (d) is unnecessary.
  • the amounts of the individual constituents are chosen such that the components are present in the resulting powder formulation in the proportions already indicated above.
  • the method according to the invention can be carried out both continuously and discontinuously.
  • a new apparatus consisting of:
  • the heat exchanger 3 is a device which enables the incoming suspension to be heated quickly to the desired temperature.
  • the jet disperser 4 is constructed in such a way that the incoming emulsion is dispersed through a nozzle.
  • the proportionality of the dispersion produced depends on
  • nozzles are used whose bores are between 0.1 and 1 mm, preferably between 0.2 and 0.7 mm.
  • the cooling circuit 5 provided with pump 6 is a device which is suitable for minimizing the cooling time of the incoming emulsion.
  • the emulsion flowing through the cooler 5 is recirculated with the aid of the pump 6 with about ten times the pumping current.
  • This cooling circuit cools the introduced emulsion in the range of milliseconds
  • the pump 7 is a metering device which is connected to the pipeline leading away from the cooling circuit.
  • An additional mixing tank with agitator can also be installed at this point in the apparatus.
  • the spray dryer 8 is a device of this type which is designed in such a way that the water can be extracted from the incoming aqueous solution.
  • the spray dryer can also be replaced by a freeze dryer.
  • the procedure is as follows: in the first step, one or more solid active ingredients, optionally in a mixture with one or more liquid active ingredients, and optionally additives in finely divided state in container 1 suspended in a mixture of water and dispersant.
  • the components can be put together in the pre-ground state.
  • the suspension produced in this way is conveyed by the pump 2 via the heat exchanger 3 into the downstream jet disperser 4.
  • the pump also has the task of building up the necessary dispersion pressure.
  • the dispersion in the heat exchanger 3 Before entering the jet disperser 4, the dispersion in the heat exchanger 3 is quickly heated to a temperature above the melting point of the solid phase, so that an emulsion is formed for a short time. This is then homogenized in finely divided form in the jet disperser 4 and cooled immediately after passing through the jet disperser in the cooling circuit system 5/6. In order to keep the cooling time as short as possible, the dispersion is fed into the cooler 5 and recirculated with the pump 6 at about ten times the pumping current. Through the cooling loop, quenching ensures that the emulsion cools down in a period of milliseconds and the active substance particles solidify amorphously.
  • an aqueous solution of polyvinyl alcohol and, if appropriate, further coating materials and / or other additives are added to the dispersion of amorphous particles via the metering pump 7.
  • the pre-stabilized solution is then immediately introduced into the spray dryer 8, where the water is removed from the dispersion and the active ingredient particles are encapsulated by the encapsulation material.
  • a free-flowing powder is created in each case.
  • the average size of the particles contained in the powder depends on the spray drying conditions. Smaller particles are created at higher pressures and larger amounts of air than when using lower pressures and smaller amounts of air.
  • the formulations according to the invention are redispersible powders which consist of finely divided active substance particles which are encapsulated by the encapsulation material, the capsules in turn being embedded in the encapsulation material.
  • the powder formulations according to the invention are stable even after prolonged storage. They can be converted into homogeneous spray liquids by stirring them into water. These spray liquids are used by customary methods, for example by spraying, pouring or injecting. It is also possible to granulate the powders . Process tablets, pastes or other dosage forms.
  • the application rate of the powder formulations according to the invention can be varied within a substantial range. It depends on the active substances present and their content in the formulations. Active ingredients can be applied in a particularly advantageous manner with the aid of the powder formulations according to the invention.
  • the active ingredients contained are readily bioavailable and develop a biological effectiveness that is significantly better than that of conventional formulations in which the active components are present in a crystalline state.
  • Tristyrylphenol ethoxylates with an average of 16 ethylene oxide units (trade name Soprophor® 3D33), 0.1 part by weight of silicone oil defoamer and 89.9 parts by weight of water
  • the suspension thus produced was pumped into a heat exchanger, heated to 108 ° C. and conveyed with a volume flow of 22 liters per hour under a homogenizing pressure of 80 bar into a jet disperser with a nozzle bore of 0.2 mm diameter.
  • Clariant mixed in water and immediately then dried over a spray dryer at an exhaust air temperature of ⁇ 80 ° C. 550 g of a free-flowing powder with an active substance content of 24.8% were obtained, the active substance being in the amorphous state.
  • Example 1 According to the method given in Example 1, a suspension of the composition listed there was subjected to jet dispersion under the conditions mentioned therein and, after cooling to 30 ° C. with 1.543 liters of a 25% by weight solution of polyvinyl alcohol (Mowiol® 3- 83 from Clariant) in
  • the suspension thus produced was pumped into a heat exchanger, heated to 110 ° C. and conveyed with a volume flow of 22 liters per hour under a homogenizing pressure of 80 bar into a jet disperser with a nozzle bore of 0.2 mm diameter.
  • the accruing Dispersion, in which the particles have an average size of 0.2 ⁇ m, was cooled to a temperature of 30 ° C.
  • the suspension produced in this way was pumped into a heat exchanger, heated to 110 ° C. and, at a volume flow of 22 liters per hour, under a homogenizing pressure of 80 bar, into a jet disperser. gator with a nozzle bore of 0.2 mm in diameter.
  • the resulting dispersion in which the particles have an average size of 0.2 ⁇ m, was cooled within a split second to a temperature of 30 ° C., then with 1.2 liters of a 25% strength by weight solution of poly - Vinyl alcohol (Mowiol® 3-83 from Clariant) mixed in water and immediately dried over a spray dryer at an exhaust air temperature of ⁇ 80 ° C. 550 g of a free-flowing powder with an active ingredient content of 24.5% were obtained, the active ingredient being in the amorphous state.
  • the suspension produced in this way was pumped into a heat exchanger, heated to 108 ° C. and, with a volume flow of 22 liters per hour, under a homogenizing pressure of 80 bar, into a jet disperser. gator with a nozzle bore of 0.2 mm in diameter.
  • the resulting dispersion, in which the particles have an average size of 0.2 ⁇ m was cooled to a temperature of 30 ° C within fractions of a second and then in dried in a spray dryer at an exhaust gas temperature of 80 ° C.
  • the production of a free-flowing powder was not successful.
  • the dried material already sticks in the dryer and has a crystalline structure.
  • the suspension produced in this way was pumped into a heat exchanger, heated to 108 ° C. and conveyed with a volume flow of 22 liters per hour under a homogenizing pressure of 80 bar into a jet disperser with a nozzle bore of 0.2 mm diameter.
  • the accruing Dispersion in which the particles have an average size of 0.2 ⁇ m was cooled to a temperature of 30 ° C. within a split second and then with a cooling circuit Amount of a 25 wt .-% solution of polyvinyl alcohol (Mowiol® 3-83 from Clariant) mixed in water that the
  • the proportion of polyvinyl alcohol in the resulting product was 15% by weight. Subsequent spray drying at an exhaust air temperature of ⁇ 80 ° C. gave 300 g of a slightly agglomerated powder with an active ingredient content of 40%. The crystalline proportion of active ingredient was 1% and increased when the product was stored.
  • Leaves were used that were cut off in the fully developed state from golden Delicious apple trees. The cuticles were isolated in such a way that.
  • leaf disks marked and punched out on the underside were first filled by vacuum infiltration with a pectinase solution (0.2 to 2%) buffered to a pH value between 3 and 4,
  • the cuticles were placed in the center with tweezers on the edges of the diffusion cells covered with silicone grease and closed with a ring that was also greased. The arrangement was chosen so that the morphological
  • the diffusion cells were filled with water or with a mixture of water and solvent.
  • Spray liquor A (according to the invention)
  • CIPAC-C water was used in each of the spray liquors.
  • test results are shown in the following table.
  • the figures given are average values from 8 measurements.
  • Dispersant 1 part by weight of the emulsifier mentioned in Example 1
  • a powder formulation according to Example 1 is diluted with water to the desired concentration with the addition of dispersant.
  • the plants are placed in a greenhouse at a temperature of approx. 18 ° C and a relative humidity of approx. 80% to prevent the development of
  • Evaluation is carried out 9 days after the inoculation. 0% means an efficiency that corresponds to that of the control, while an efficiency of 100% means that no infection is observed.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pest Control & Pesticides (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Biomedical Technology (AREA)
  • Nanotechnology (AREA)
  • Optics & Photonics (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne de nouvelles formulations pulvérulentes de principes actifs contenant au moins un principe actif solide à température ambiante, au moins un agent dispersant, un alcool polyvinylique et éventuellement des adjuvants. Les particules de principe actif sont individuellement enrobées d'une couche d'alcool polyvinylique ; elles se présentent à l'état amorphe et leur diamètre se situe dans la plage nanométrique. L'invention concerne également un procédé de production de ces nouvelles formulations et leur utilisation pour l'application des principes actifs ainsi qu'un dispositif destiné à la mise en oeuvre du procédé de production.
EP02774722A 2001-10-18 2002-10-17 Formulations pulverulentes de principes actifs Withdrawn EP1571906A2 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10151392A DE10151392A1 (de) 2001-10-18 2001-10-18 Pulverförmige Feststoff-Formulierungen
DE10151392 2001-10-18
PCT/EP2002/011613 WO2003034822A2 (fr) 2001-10-18 2002-10-17 Formulations pulverulentes de principes actifs

Publications (1)

Publication Number Publication Date
EP1571906A2 true EP1571906A2 (fr) 2005-09-14

Family

ID=7702888

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02774722A Withdrawn EP1571906A2 (fr) 2001-10-18 2002-10-17 Formulations pulverulentes de principes actifs

Country Status (6)

Country Link
US (1) US20060165742A1 (fr)
EP (1) EP1571906A2 (fr)
JP (1) JP2005519869A (fr)
AU (1) AU2002340573A1 (fr)
DE (1) DE10151392A1 (fr)
WO (1) WO2003034822A2 (fr)

Cited By (1)

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US10422531B2 (en) 2012-09-15 2019-09-24 Honeywell International Inc. System and approach for controlling a combustion chamber

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DE10351087A1 (de) * 2003-10-31 2005-05-25 Bayer Technology Services Gmbh Feste Wirkstoff-Formulierung
DE102004020840A1 (de) * 2004-04-27 2005-11-24 Bayer Cropscience Ag Verwendung von Alkylcarbonsäureamiden als Penetrationsförderer
DE102004026745B4 (de) * 2004-05-28 2013-06-20 Justus-Liebig-Universität Giessen Verfahren und Vorrichtung zur Ausbringung von nanoskaligen Polymerfasern als Träger für landwirtschaftliche Wirkstoffe
ES2383820T3 (es) * 2005-09-09 2012-06-26 Bayer Cropscience Ag Formulaciones sólidas de mezclas de fungicidas
US9668476B2 (en) * 2006-02-23 2017-06-06 Lanxess Corporation Removable antimicrobial coating compositions and methods of use
GB0613925D0 (en) * 2006-07-13 2006-08-23 Unilever Plc Improvements relating to nanodispersions
AR063704A1 (es) * 2006-09-14 2009-02-11 Makhteshim Chem Works Ltd Nanoparticulas de pesticida obtenida obtenidas a partir de microemulsiones y nanoemulsiones
WO2008032327A2 (fr) * 2006-09-14 2008-03-20 Yissum Research Development Company Of The Hebrew University Of Jerusalem Nanoparticules organiques obtenues à partir de microémulsions par évaporation de solvant
JP5290188B2 (ja) * 2006-11-30 2013-09-18 ビーエーエスエフ ソシエタス・ヨーロピア ジイソシアネートをベースとしたコポリマーを含む農薬製剤
US8735321B2 (en) 2008-05-09 2014-05-27 Basf Se Process for the production of particles comprising active agrochemical ingredients in amorphous form
US20110177146A1 (en) * 2009-07-27 2011-07-21 E. I. Du Pont De Nemours And Company Removable antimicrobial coating compositions containing cationic rheology agent and methods of use
CN103889217A (zh) * 2011-08-25 2014-06-25 陶氏益农公司 在有害生物防治区域中具有增强的活性成分保持力的农药组合物
EP3210468A1 (fr) 2016-02-26 2017-08-30 Bayer CropScience Aktiengesellschaft Compositions sans solvant pour agents actifs a bas point de fusion

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Publication number Priority date Publication date Assignee Title
US10422531B2 (en) 2012-09-15 2019-09-24 Honeywell International Inc. System and approach for controlling a combustion chamber
US11421875B2 (en) 2012-09-15 2022-08-23 Honeywell International Inc. Burner control system

Also Published As

Publication number Publication date
WO2003034822A2 (fr) 2003-05-01
US20060165742A1 (en) 2006-07-27
AU2002340573A8 (en) 2008-02-28
DE10151392A1 (de) 2003-05-08
JP2005519869A (ja) 2005-07-07
WO2003034822A3 (fr) 2007-12-06
AU2002340573A1 (en) 2003-05-06

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