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WO2003007712A1 - Streptomycin-containing granules and process for the preparation thereof - Google Patents

Streptomycin-containing granules and process for the preparation thereof Download PDF

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Publication number
WO2003007712A1
WO2003007712A1 PCT/EP2002/008076 EP0208076W WO03007712A1 WO 2003007712 A1 WO2003007712 A1 WO 2003007712A1 EP 0208076 W EP0208076 W EP 0208076W WO 03007712 A1 WO03007712 A1 WO 03007712A1
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WO
WIPO (PCT)
Prior art keywords
antibiotic
granules
water
process according
salt
Prior art date
Application number
PCT/EP2002/008076
Other languages
French (fr)
Inventor
Wolfgang Kempe
Constant Johan Van Lookeren Campagne
Original Assignee
Dsm Ip Assets B.V.
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 Dsm Ip Assets B.V. filed Critical Dsm Ip Assets B.V.
Publication of WO2003007712A1 publication Critical patent/WO2003007712A1/en

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Classifications

    • 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
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44—Guanidine; Derivatives thereof

Definitions

  • the present invention relates to the formulation of agricultural antibiotics. More specifically, the present invention discloses an antibiotic-containing water dispersible granule for application in crop protection and methods for the preparation thereof.
  • Fire blight is a destructive infectious fruit disease caused by the bacterium Erwinia amylovora. The disease kills blossoms, fruit, shoots, limbs and tree trunks and is characterized by its fast infection patterns leading to a scorched appearance of the foliage and branches it leaves behind. Following a heavy outbreak of fire blight in the early nineties in Southwest Germany, application of the antibiotic streptomycin has been allowed during bloom of apple and pear since 1994.
  • streptomycin The main drawbacks of the use of streptomycin are that severe risks are taken with regard to dust-inhalation incidences with workers during preparation of the liquid to be sprayed, using state of the art powder formulations.
  • the well known wettable powder formulations of streptomycin have led to unwanted exposure of users to dust when opening packages and preparing the spray.
  • continuous use has led to increased residues of streptomycin found in honey collected by bees in orchards that were treated with streptomycin sprays. These effects can easily give rise to resistance problems. Because of this resistance issue, all existing antibiotic formulations for agricultural purposes were eventually banned in some European countries, such as Germany.
  • a possible solution to this problem is formulating the antibiotic in dust-free granules that are dispersible in water and can be applied in the spraying equipment.
  • Water dispersible granules containing active chemical components with herbicidal-, fungicidal-, or insecticidal modes of action for application in crop-protection and processes for making such granules are known from International Patent Application WO89/00079.
  • the particular problem in making these antibiotic-containing granules for crop protection is that they have to fulfill many performance criteria, which are often narrowly defined, such as dispersibility, flowability, low dust content, particle size distribution, shelf life, and solubility.
  • a novel granule and a process for the preparation of said granule is disclosed. Surprisingly, this granule provides a controlled release of the antibiotic and complies with all of the abovementioned specifications that are to be met.
  • a process for the preparation of an antibiotic-containing granule suitable for use in crop protection the antibiotic-containing granules are obtained by mixing the desired ingredients of the granules in a form suitable for application in a granulator. After mixing, the granulation is performed and the resulting granules are dried.
  • the second aspect of the present invention relates to antibiotic-containing granules obtainable by the process of the first aspect, which seeks to solve the problems encountered in the prior art.
  • the ingredients of the granule comprise an antibiotic, a water-insoluble carrier, a water-soluble salt of an alkaline (-earth) metal and/or an ammonium salt, water, optionally one or more thickening agents, optionally one or more tracer molecules, and optionally one or more surfactants.
  • w/w is defined as the amount relative to the total weight of the granule after drying, unless specified otherwise.
  • a dried granule may contain residual water ranging from 1 -8% (w/w).
  • Antibiotics are substances from all classes of compounds that are known to have antibiotic activity against bacteria, such as amino glycosides, ⁇ -lactams, macrolides, quinolones, tetracyclines, and salts and esters thereof.
  • Preferred antibiotics are amino glycosides such as streptomycin and its salts and quinolones such as flumequine.
  • the amount of antibiotic as present in the granule should be at least 10% (w/w), preferably at least 15% (w/w), more preferably at least 20% (w/w). Upper levels of antibiotic are influenced by the amounts of other components in the mixture.
  • the amount of carrier ranges from a minimal value of 1-30% (w/w), preferably 20-30% (w/w), more preferably 25-30% (w/w), to a maximal value of 30-80% (w/w), preferably 30-50% (w/w), more preferably 30-40% (w/w).
  • the carrier has an Al 2 0 3 content ranging from a minimal value of 5-35% (w/w), preferably 20-35% (w/w), more preferably 30-35% (w/w), to a maximal value of 35-65% (w/w), preferably 35-50% (w/w), more preferably 35-40% (w/w).
  • the carrier may further contain SiO 2 , its content ranging from a minimal value of 20-50% (w/w), preferably 35-50% (w/w), more preferably 45-50% (w/w), to a maximal value of 50-80% (w/w), preferably 50-65% (w/w), more preferably 50-55% (w/w).
  • the SiO 2 may be present naturally or added to the carrier.
  • the carrier should have an aluminum oxide content of more than 35% (w/w) and be added such, that the ratio of aluminum oxide/antibiotic in the granule is at least 0.1 (w/w), preferably at least 0.2 (w/w), more preferably at least 0.3 (w/w), still more preferably at least 0.4 (w/w), most preferably at least 0.5 (w/w).
  • the upper limit of said ratio is limited by physical boundaries, as the person skilled in the art will understand.
  • a substantial part of the carrier particles should have a particle size ranging from 2 ⁇ m to 10 ⁇ m.
  • the granule further contains a water-soluble salt of an alkaline (-earth) metal and/or an ammonium salt.
  • a salt for instance is ammonium benzoate, ammonium sulfate, magnesium sulfate, potassium benzoate, potassium sulfate (K 2 SO 4 ), sodium benzoate, sodium chloride, and/or sodium sulfate.
  • the salt can be a single salt or a mixture of more than one salt.
  • the salt is added in order to improve the processing and storage stability of the dry antibiotic granulates and/or to improve the antimicrobial and/or antifungal properties of the antibiotic granulates.
  • a preferred water-soluble salt of an alkaline (-earth) metal is K 2 SO 4 .
  • the person skilled in the art will understand that salt can be added as such but can also, in some cases, be formed in situ by addition of the corresponding acid at any point during the mixing process.
  • the amount of salt ranges from a minimal value of 1-20% (w/w), preferably 10-
  • thickening agent is used in the broad sense and includes materials that can improve the pelleting stabilization. Suitable thickening agents are hydroxylated or carboxylated cellulose, polysaccharides such as alginates and gums, biopolymers such as xanthan gum, and polycarboxylates such as sodium polycarboxylate.
  • the thickening agent is sodium polycarboxylate based Geropon T/36, the amount ranging from a minimal value of 1-25% (w/w), preferably 15-25% (w/w), more preferably 20-25% (w/w), to a maximal value of 25-50% (w/w), preferably 25-35% (w/w), more preferably 25-30% (w/w).
  • surfactant is used in the broad sense to include materials, which may be referred to as emulsifying agents, dispersing agents, and wetting agents.
  • the surfactant component may comprise one or more surfactants from the anionic, cationic and/or non-ionic type.
  • anionic surfactants are aliphatic sulfonic ester salts like lauryl sulfate, aromatic sulfonic acid salts, salts of lignosulfates, and soaps.
  • non- ionic surfactants are the condensation products of ethylene oxide with fatty alcohols such as oleylalcohol, alkyl phenols, lecithins, and phosphorylated surfactants such as phosphorylated ethylene oxide/propylene oxide block copolymer and ethoxylated and phosphorylated styryl-substituted phenol.
  • Preferred surfactants are anionic wetting agents such as sodium salts of sulfated alkyl carboxylate, and/or alkyl naphtalenesulphonate and/or dispersing agents such as naphthalene formaldehyde condensate.
  • the amount of surfactant ranges from a minimal value of 0.1-1% (w/w) to a maximal value of 1-10% (w/w).
  • Water is added to the mixture of ingredients to be processed to granules to improve the mixing granulation process.
  • the order of addition of the ingredients is not a critical parameter, although it is well known that gradual addition of water often leads to the best mixing results.
  • the amount of added water typically is determined by the process conditions.
  • the mixing of the antibiotic, the carrier, and water may additionally comprise kneading of the mixture. This may improve the plasticity of the mixture in order to facilitate granulation (e.g. extrusion).
  • the mechanical processes that are applied in the present invention for processing the mixture of the antibiotic, water and the solid carrier into granules are frequently used in food, feed and enzyme formulation processes, where they occur in a number of ways such as drum granulation, expansion, extrusion, fluid bed agglomeration, high shear granulation, pelleting, spheronization, or a combination thereof.
  • These processes are characterized by an input of mechanical energy, such as the drive of a screw, the rotation of a mixing mechanism, the pressure of a rolling mechanism of a pelleting apparatus, the movement of particles by a rotating bottom plate of a fluid bed agglomerator or the movement of the particles by a gas stream, or a combination thereof.
  • These processes allow the solid carrier (e.g.
  • the solid carrier can be mixed with the antibiotic (e.g. in a powder form) to which water is added, which acts as granulating liquid.
  • the granule e.g. an agglomerate
  • the granule is formed by spraying an antibiotic-containing liquid onto the carrier in a fluid bed agglomerator.
  • the resulting granules can include an agglomerate as can be produced in a fluid bed agglomerator.
  • the granules are formed by extrusion. Preferably, extrusion is performed at low pressure.
  • Low-pressure extrusion offers the advantage that the temperature in the extruded mixture will not, or only slightly, increase.
  • Low-pressure extrusion includes extrusion in, for example, a Fuji Paudal basket- or dome-extruder.
  • the extrusion may naturally produce granules (the granules may break off after passage through a die) or a cutting device may be employed.
  • the granulator is a low-pressure basket extruder equipped with a perforated screen and a temperature indicator.
  • the diameter of the holes ranges has a minimal value of 0.2-1.2 mm, more preferably 0.8-1.2 mm, most preferably 1.0-1.2 mm.
  • the maximal value of the holes is 1.2-2.5 mm, more preferably 1.2-1.6 mm, most preferably 1.2-1.4 mm.
  • the temperature of the extrusion process can be controlled by increasing or reducing the speed of the paddles and has a minimal value of 5-40°C, preferably 25-40°C, more preferably 35-40°C.
  • the maximal temperature value is 40-75°C, preferably 50-65°C, more preferably 55-60°C.
  • the granules obtained can be subjected to rounding off (e.g. spheronization), such as in an spheronizer, e.g. a MarumeriserTM machine and/or compaction machine.
  • the granules can be spheronized prior to drying since this may reduce dust formation in the final granules and/or may facilitate any coating of the granules.
  • the granules can then be dried, such as in a fluid bed drier or, in case of the fluid bed agglomeration, can be immediately dried (in the agglomerator) to obtain (solid dry) granules.
  • Other known methods for drying granules in the food, feed or enzyme industry can be used by the skilled person.
  • the granules are flowable.
  • the discharged particles are dried using a fluid bed drier.
  • Particles are dried to a final moisture content that has a minimal value of 0.5-2.5% (w/w), preferably 1.5-2.5% (w/w), more preferably 2.0-2.5% (w/w).
  • the maximal value of the moisture content is 2.5-10% (w/w), preferably 2.5-5.0% (w/w), more preferably 2.5-3.0% (w/w).
  • the third aspect of the present invention relates to the use of the granules of the second aspect dispersed in, or as a component of, a fluid that is applied to crops, fruit, plants or trees using spraying or pouring equipment with the aim of preventing, suppressing, or treating infectious diseases in agriculture such as fire blight.
  • Geropon T/36 a sodium polycarboxylate based thickening agent.
  • Morwet EFW a wetting agent containing sodium salts of sulfated alkyl carboxylate and alkyl naphtalenesulphonate - 4.0 kg Morwet D245 dispersing agent, a naphtalene formaldehyde condensate
  • the formulated streptomycin sulfate water dispersible granule has the following properties:
  • Geropon T/36 a sodium polycarboxylate based thickening agent.
  • 5.0 Kg Morwet EFW a wetting agent containing sodium salts of sulfated alkyl carboxylate and alkyl naphtalenesulphonate - 15.0 Kg Morwet D245 dispersing agent, a naphtalene formaldehyde condensate
  • the formulated streptomycin sulfate water dispersible granule has the following properties:

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  • Life Sciences & Earth Sciences (AREA)
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Abstract

The present invention provides a process for the preparation of an antibiotic-containing water dispersible granule suitable for use in crop protection and antibiotic-containing water dispersible granules obtainable by said process. Furthermore, the present invention relates to the use of said granules dispersed in, or as a component of, a fluid that is applied to crops, fruit, plants or trees using spraying or pouring equipment with the aim of preventing, suppressing, or treating infectious diseases in agriculture, such as fire blight. The process comprises processing an antibiotic or a salt thereof, a water-insoluble aluminum oxide containing carrier, a water-soluble salt of an alkaline (-earth) metal and/or an ammonium salt, water, and optionally surfactants and thickening agents to obtain antibiotic-containing granules, and drying the granules, characterized in that the ratio aluminum oxide/antibiotic is at least 0.1 (w/w) and the amount of antibiotic in the antibiotic-containing granules is at least 10% (w/w).

Description

STREPTOMYCIN-CONTAINING GRANULES AND PROCESS FOR THE
PREPARATION THEREOF
Field of the invention
The present invention relates to the formulation of agricultural antibiotics. More specifically, the present invention discloses an antibiotic-containing water dispersible granule for application in crop protection and methods for the preparation thereof.
Background of the invention
Fire blight is a destructive infectious fruit disease caused by the bacterium Erwinia amylovora. The disease kills blossoms, fruit, shoots, limbs and tree trunks and is characterized by its fast infection patterns leading to a scorched appearance of the foliage and branches it leaves behind. Following a heavy outbreak of fire blight in the early nineties in Southwest Germany, application of the antibiotic streptomycin has been allowed during bloom of apple and pear since 1994.
The main drawbacks of the use of streptomycin are that severe risks are taken with regard to dust-inhalation incidences with workers during preparation of the liquid to be sprayed, using state of the art powder formulations. The well known wettable powder formulations of streptomycin have led to unwanted exposure of users to dust when opening packages and preparing the spray. Furthermore, continuous use has led to increased residues of streptomycin found in honey collected by bees in orchards that were treated with streptomycin sprays. These effects can easily give rise to resistance problems. Because of this resistance issue, all existing antibiotic formulations for agricultural purposes were eventually banned in some European countries, such as Germany.
A possible solution to this problem is formulating the antibiotic in dust-free granules that are dispersible in water and can be applied in the spraying equipment. Water dispersible granules containing active chemical components with herbicidal-, fungicidal-, or insecticidal modes of action for application in crop-protection and processes for making such granules are known from International Patent Application WO89/00079. The particular problem in making these antibiotic-containing granules for crop protection is that they have to fulfill many performance criteria, which are often narrowly defined, such as dispersibility, flowability, low dust content, particle size distribution, shelf life, and solubility. However, the current methods for producing granules are not sufficient to prepare a product that can fulfill the registration and safety criteria with respect to antibiotic residues and food safety, antibiotic dust exposure during spraying, and environmental safety. According to the present invention, a novel granule and a process for the preparation of said granule is disclosed. Surprisingly, this granule provides a controlled release of the antibiotic and complies with all of the abovementioned specifications that are to be met.
Detailed description of the invention
In a first aspect of the present invention there is provided a process for the preparation of an antibiotic-containing granule suitable for use in crop protection. According to the invention, the antibiotic-containing granules are obtained by mixing the desired ingredients of the granules in a form suitable for application in a granulator. After mixing, the granulation is performed and the resulting granules are dried. The second aspect of the present invention relates to antibiotic-containing granules obtainable by the process of the first aspect, which seeks to solve the problems encountered in the prior art.
The ingredients of the granule comprise an antibiotic, a water-insoluble carrier, a water-soluble salt of an alkaline (-earth) metal and/or an ammonium salt, water, optionally one or more thickening agents, optionally one or more tracer molecules, and optionally one or more surfactants.
Throughout the description of the invention, the term w/w is defined as the amount relative to the total weight of the granule after drying, unless specified otherwise. Typically, a dried granule may contain residual water ranging from 1 -8% (w/w).
Antibiotics are substances from all classes of compounds that are known to have antibiotic activity against bacteria, such as amino glycosides, β-lactams, macrolides, quinolones, tetracyclines, and salts and esters thereof. Preferred antibiotics are amino glycosides such as streptomycin and its salts and quinolones such as flumequine. The amount of antibiotic as present in the granule should be at least 10% (w/w), preferably at least 15% (w/w), more preferably at least 20% (w/w). Upper levels of antibiotic are influenced by the amounts of other components in the mixture. Typically, the amount of antibiotic as present in the granule has a minimal value of 10-25% (w/w), preferably 15-25% (w/w), more preferably 20-25% (w/w), and a maximal value of 25-60% (w/w), preferably 25-50% (w/w), more preferably 25-40% (w/w), most preferably 25-30% (w/w).
The term carrier as used throughout this invention is defined as an aluminum oxide (AI2O3) containing water insoluble material that is capable of absorbing the antibiotic. The carrier may be aluminum oxide, attaclay, bentonite, bole, calcium carbonate, calcium sulfate, celite, chalk, diatomaceous earth, dolomite, Fuller's earth, gypsum, kaolin clay, kieselguhr, lime, limestone, loss, magnesia (powdered), magnesium oxide, pyrophyllite, silica gels, silicates, silicic acid, silicium oxide (SiO2), and/or talc, alone or in combinations with one another. In case the carrier does not naturally contain AI2O3, AI2O3 should be added to the carrier. More preferred carriers are kaolin clay, Al203 and/or SiO2. Most preferably, the carrier is kaolin clay. Preferably, the specific surface area of the kaolin clay is 8-10 m2/g, more preferably 9 m2/g
The amount of carrier ranges from a minimal value of 1-30% (w/w), preferably 20-30% (w/w), more preferably 25-30% (w/w), to a maximal value of 30-80% (w/w), preferably 30-50% (w/w), more preferably 30-40% (w/w).
In one embodiment of the invention, the carrier has an Al203 content ranging from a minimal value of 5-35% (w/w), preferably 20-35% (w/w), more preferably 30-35% (w/w), to a maximal value of 35-65% (w/w), preferably 35-50% (w/w), more preferably 35-40% (w/w). In another embodiment, the carrier may further contain SiO2, its content ranging from a minimal value of 20-50% (w/w), preferably 35-50% (w/w), more preferably 45-50% (w/w), to a maximal value of 50-80% (w/w), preferably 50-65% (w/w), more preferably 50-55% (w/w). The SiO2 may be present naturally or added to the carrier.
In a preferred embodiment of the invention, the carrier should have an aluminum oxide content of more than 35% (w/w) and be added such, that the ratio of aluminum oxide/antibiotic in the granule is at least 0.1 (w/w), preferably at least 0.2 (w/w), more preferably at least 0.3 (w/w), still more preferably at least 0.4 (w/w), most preferably at least 0.5 (w/w). The upper limit of said ratio is limited by physical boundaries, as the person skilled in the art will understand. In yet another embodiment of the invention, a substantial part of the carrier particles should have a particle size ranging from 2 μm to 10 μm. Preferably, less than 40% (w/w) of the carrier should have a particle size <2 μm and less than 25% (w/w) of the clay should have a particle size >10 μm. The granule further contains a water-soluble salt of an alkaline (-earth) metal and/or an ammonium salt. Such a salt for instance is ammonium benzoate, ammonium sulfate, magnesium sulfate, potassium benzoate, potassium sulfate (K2SO4), sodium benzoate, sodium chloride, and/or sodium sulfate. The salt can be a single salt or a mixture of more than one salt. The salt is added in order to improve the processing and storage stability of the dry antibiotic granulates and/or to improve the antimicrobial and/or antifungal properties of the antibiotic granulates. A preferred water-soluble salt of an alkaline (-earth) metal is K2SO4. The person skilled in the art will understand that salt can be added as such but can also, in some cases, be formed in situ by addition of the corresponding acid at any point during the mixing process. The amount of salt ranges from a minimal value of 1-20% (w/w), preferably 10-
20% (w/w), more preferably 15-20% (w/w), to a maximal value of 20-70% (w/w), preferably 20-40% (w/w), more preferably 20-25% (w/w).
The term thickening agent is used in the broad sense and includes materials that can improve the pelleting stabilization. Suitable thickening agents are hydroxylated or carboxylated cellulose, polysaccharides such as alginates and gums, biopolymers such as xanthan gum, and polycarboxylates such as sodium polycarboxylate. In a preferred embodiment the thickening agent is sodium polycarboxylate based Geropon T/36, the amount ranging from a minimal value of 1-25% (w/w), preferably 15-25% (w/w), more preferably 20-25% (w/w), to a maximal value of 25-50% (w/w), preferably 25-35% (w/w), more preferably 25-30% (w/w).
A tracer may be added in order to determine the fate of the granule and/or its components, for instance into the environment. The term tracer is used in the broad sense to include materials, which may be detected at relatively low concentrations using analytical techniques that are well known to the person skilled in the art, whilst simultaneously have no effect on the properties of the antibiotic granules. A preferred tracer is caffeine.
The term surfactant is used in the broad sense to include materials, which may be referred to as emulsifying agents, dispersing agents, and wetting agents. The surfactant component may comprise one or more surfactants from the anionic, cationic and/or non-ionic type.
Examples of anionic surfactants are aliphatic sulfonic ester salts like lauryl sulfate, aromatic sulfonic acid salts, salts of lignosulfates, and soaps. Examples of non- ionic surfactants are the condensation products of ethylene oxide with fatty alcohols such as oleylalcohol, alkyl phenols, lecithins, and phosphorylated surfactants such as phosphorylated ethylene oxide/propylene oxide block copolymer and ethoxylated and phosphorylated styryl-substituted phenol. Preferred surfactants are anionic wetting agents such as sodium salts of sulfated alkyl carboxylate, and/or alkyl naphtalenesulphonate and/or dispersing agents such as naphthalene formaldehyde condensate.
The amount of surfactant ranges from a minimal value of 0.1-1% (w/w) to a maximal value of 1-10% (w/w).
Water is added to the mixture of ingredients to be processed to granules to improve the mixing granulation process. The order of addition of the ingredients is not a critical parameter, although it is well known that gradual addition of water often leads to the best mixing results. The amount of added water typically is determined by the process conditions. The mixing of the antibiotic, the carrier, and water may additionally comprise kneading of the mixture. This may improve the plasticity of the mixture in order to facilitate granulation (e.g. extrusion).
The mechanical processes that are applied in the present invention for processing the mixture of the antibiotic, water and the solid carrier into granules, are frequently used in food, feed and enzyme formulation processes, where they occur in a number of ways such as drum granulation, expansion, extrusion, fluid bed agglomeration, high shear granulation, pelleting, spheronization, or a combination thereof. These processes are characterized by an input of mechanical energy, such as the drive of a screw, the rotation of a mixing mechanism, the pressure of a rolling mechanism of a pelleting apparatus, the movement of particles by a rotating bottom plate of a fluid bed agglomerator or the movement of the particles by a gas stream, or a combination thereof. These processes allow the solid carrier (e.g. in the form of a powder), to be mixed with the antibiotic and water, and subsequently form a granule. Alternatively the solid carrier can be mixed with the antibiotic (e.g. in a powder form) to which water is added, which acts as granulating liquid. In yet a further embodiment of the invention the granule (e.g. an agglomerate) is formed by spraying an antibiotic-containing liquid onto the carrier in a fluid bed agglomerator. Here, the resulting granules can include an agglomerate as can be produced in a fluid bed agglomerator. In a preferred embodiment of the invention, the granules are formed by extrusion. Preferably, extrusion is performed at low pressure. Low-pressure extrusion offers the advantage that the temperature in the extruded mixture will not, or only slightly, increase. Low-pressure extrusion includes extrusion in, for example, a Fuji Paudal basket- or dome-extruder. The extrusion may naturally produce granules (the granules may break off after passage through a die) or a cutting device may be employed.
In a preferred embodiment of the invention, the granulator is a low-pressure basket extruder equipped with a perforated screen and a temperature indicator. Preferably, the diameter of the holes ranges has a minimal value of 0.2-1.2 mm, more preferably 0.8-1.2 mm, most preferably 1.0-1.2 mm. Preferably, the maximal value of the holes is 1.2-2.5 mm, more preferably 1.2-1.6 mm, most preferably 1.2-1.4 mm. The temperature of the extrusion process can be controlled by increasing or reducing the speed of the paddles and has a minimal value of 5-40°C, preferably 25-40°C, more preferably 35-40°C. The maximal temperature value is 40-75°C, preferably 50-65°C, more preferably 55-60°C.
The granules obtained can be subjected to rounding off (e.g. spheronization), such as in an spheronizer, e.g. a Marumeriser™ machine and/or compaction machine. The granules can be spheronized prior to drying since this may reduce dust formation in the final granules and/or may facilitate any coating of the granules. The granules can then be dried, such as in a fluid bed drier or, in case of the fluid bed agglomeration, can be immediately dried (in the agglomerator) to obtain (solid dry) granules. Other known methods for drying granules in the food, feed or enzyme industry can be used by the skilled person. Suitably the granules are flowable.
In a preferred embodiment, the discharged particles are dried using a fluid bed drier. Particles are dried to a final moisture content that has a minimal value of 0.5-2.5% (w/w), preferably 1.5-2.5% (w/w), more preferably 2.0-2.5% (w/w). The maximal value of the moisture content is 2.5-10% (w/w), preferably 2.5-5.0% (w/w), more preferably 2.5-3.0% (w/w). The third aspect of the present invention relates to the use of the granules of the second aspect dispersed in, or as a component of, a fluid that is applied to crops, fruit, plants or trees using spraying or pouring equipment with the aim of preventing, suppressing, or treating infectious diseases in agriculture such as fire blight.
The invention is illustrated by, and not limited to, the following examples.
EXAMPLES
Example 1
The following ingredients are weighed into a 200 I high shear mixer (Type Glatt VG 800) and blended for a period of 60 sec. with a rotational speed of the paddles of 52 rpm:
22.5 kg 99.5% active ingredient streptomycin sulfate technical grade as supplied.
22.5 kg Geropon T/36, a sodium polycarboxylate based thickening agent.
1.0 kg Morwet EFW, a wetting agent containing sodium salts of sulfated alkyl carboxylate and alkyl naphtalenesulphonate - 4.0 kg Morwet D245 dispersing agent, a naphtalene formaldehyde condensate
20 kg potassium sulfate
30 kg Kaolin GTY Clay of the following specification:
Brightness (ISO): 77.0 + 2.0
+300 mesh (% max.): 0.05
+10 microns (% max.): 25
-2 microns (% min.): 40
Moisture (% max. as produced): 1.5 pH: 5.0 + 0.5 and the following properties:
Specific gravity: 2.6
Surface area (BET; m2/g): 9
SiO2 (X-ray fluorescence; %): 50
AI2O3 (X-ray fluorescence; %): 35 To the above specified 100 Kg dry mix 15 Kg of water is added, such that the wet mixture has a dry matter content of 16%, and mixing was continued until a homogeneous dough was obtained. The extrusion was carried out with a low-pressure basket extruder equipped with a perforated screen with holes of 1.2 mm and a temperature indicator to control the temperature of the extrudate at less than 40°C, by reducing the speed of the paddles pressing the mixture through the screen.
Subsequently, the extruded strings of the blended mixture are divided and split by a rotating plate of a spheronizer, and the discharged particles are collected and fed into a fluid bed drier and dried at the following conditions: Air inlet temperature: 80 °C
Product temperature: 43 °C
Drying time: 28 min.
Final moisture content: 2.5%
The formulated streptomycin sulfate water dispersible granule has the following properties, after sieving over a 1.4 mm and a 2.0 mm sieve.
Sieve analysis: 2.0 mm <100%< 1.0
Dispersibility (following CIPAO): > 60% in susp. after 30 minutes
Wettability: < 2 minutes Wet sieve residue: < 2%
Dust content CIPAC MT 171 : < 0.1 %
Example 2
The following ingredients are weighed into a 200 I high shear mixer (Type Glatt VG 800) and blended for a period of 60 sec. with a rotational speed of the paddles of rpm:
20.0 kg 99.5% active ingredient streptomycin sulfate technical grade as supplied. - 20.0 kg Geropon T/36, a sodium polycarboxylate based thickening agent.
5 kg Morwet EFW, a wetting agent containing sodium salts of sulfated alkyl carboxylate and alkyl naphtalenesulphonate
10 kg Morwet D245 dispersing agent, a naphtalene formaldehyde condensate 20 kg ammonium sulfate 25 kg Kaolin GTY Clay of the following specification:
Brightness (ISO): 77.0 ± 2.0
+300 mesh (% max.): 0.05
+10 microns (% max.): 25
-2 microns (% min.): 40
Moisture (% max. as produced): 1.5 pH: 5.0 ± 0.5 and the following properties:
Specific gravity: 2.6
Surface area (BET; m2/g): 9
Si02 (X-ray fluorescence; %): 50
AI2O3 (X-ray fluorescence; %): 35
To the above specified 100 Kg dry mix 15 Kg of water is added, and mixing was continued until homogeneous dough was obtained. The extrusion was carried out with a low-pressure basket extruder equipped with a perforated screen with holes of 1.2 mm and a temperature indicator to control the temperature of the extrudate at less than
40°C, by reducing the speed of the paddles pressing the mixture through the screen.
Subsequently, the extruded strings of the blended mixture are divided and split by a rotating plate of a spheronizer, and the discharged particles are collected and fed into a fluid bed drier and dried at the following conditions: Air inlet temperature: 80 °C
Product temperature: 43 °C
Drying time: 28 min. Final moisture content: 2.5%
The formulated streptomycin sulfate water dispersible granule has the following properties:
Sieve analysis: 2.0 mm <100%< 1.0 mm Dispersibility (following CIPAO): > 44% in susp. after 30 minutes
Wettability: < 2 minutes
Wet sieve residue: < 2%
Dust content CIPAC MT 171 : < 0.1 % Example 3
The following ingredients are weighed into a high shear mixer (Type VG 800) and blended for a period 60 sec. with a rotational speed of the paddles of 52 rpm: - 20.0 Kg 99.5% active ingredient streptomycin sulfate technical grade as supplied.
25.0 Kg Geropon T/36, a sodium polycarboxylate based thickening agent. 5.0 Kg Morwet EFW, a wetting agent containing sodium salts of sulfated alkyl carboxylate and alkyl naphtalenesulphonate - 15.0 Kg Morwet D245 dispersing agent, a naphtalene formaldehyde condensate
30.0 Kg Celite 209 of the following properties:
Wet density (g.1-1): 385
45 micron residue (%) 0.09
Blue light reflectance (%) 78.5
Oil absorption (%) 133.1 pH (10% slurry) 9.0
SiO2 (%): 84.5
AI2O3 (%): 0.84
5 Kg Kaolin GTY Clay of the following s pecification:
Brightness (ISO): 77.0 ± 2.0
+300 mesh (% max.): 0.05
+10 microns (% max.): 25
-2 microns (% min.): 40
Moisture (% max. as produced): 1.5 pH: 5.0 ± 0.5 and the following properties:
Specific gravity: 2.6
Surface area (BET; m2/g): 9
SiO2 (X-ray fluorescence; %): 50
AI2O3 (X-ray fluorescence; %): 35
To the above-specified 1000 g dry mix 150 g of water is added, such that the wet mixture has a dry matter content of 16%, just before extrusion. The extrusion was carried out with a low-pressure basket extruder equipped with a perforated screen with holes of 1.2 mm and a temperature indicator to control the temperature of the extrudate at less than 40°C, by reducing the speed of the paddles pressing the mixture through the screen.
Subsequently, the extruded strings of the blended mixture are divided and split by a rotating plate of a spheronizer, and the discharged particles are collected and fed into a fluid bed drier and dried at the following conditions: Air inlet temperature: 80 °C
Product temperature: 43 °C
Drying time: 28 min. Final moisture content: 2.5%
The formulated streptomycin sulfate water dispersible granule has the following properties:
Sieve analysis: 2.0 mm <100%< 1.0 mm Dispersibility (following CIPAO): > 60% in susp. after 30 minutes
Wettability: < 8 minutes
Wet sieve residue: < 2%
Dust content CIPAC MT 171 : < 0.1 %

Claims

1. A process for the preparation of granules suitable for use in crop protection, the process comprising processing an antibiotic or a salt thereof, a water-insoluble aluminum oxide-containing carrier, a water-soluble salt of an alkaline (-earth) metal and/or an ammonium salt, water, and optionally surfactants and thickening agents to obtain antibiotic-containing granules, and drying the granules, characterized in that the ratio aluminum oxide/antibiotic is at least 0.1 (w/w) and the amount of antibiotic in the antibiotic-containing granules is at least 10% (w/w).
2. A process according to claim 1 wherein the amount of antibiotic in the antibiotic- containing granules is at least 15% (w/w).
3. A process according to claim 1 wherein the amount of antibiotic in the antibiotic- containing granules is at least 20% (w/w).
4. A process according to any one of the preceding claims wherein the antibiotic is an amino glycoside.
5. A process according to claim 4 wherein the amino glycoside is streptomycin or a salt or derivative thereof.
6. A process according to any one of the preceding claims wherein the carrier has an aluminum oxide content ranging from a minimal value of 5-35% (w/w) to a maximal value of 35-65% (w/w) and wherein the carrier has a silicium oxide content ranging from a minimal value of 20-50% (w/w) to a maximal value of 50-80% (w/w).
7. A process according to any one of the preceding claims wherein the water- insoluble aluminum oxide-containing carrier is a kaolin clay.
8. A process according to any one of the preceding claims wherein the water- soluble salt comprises an alkaline (-earth) metal and/or an ammonium salt of benzoic acid.
9. A process according to any one of the preceding claims wherein the granules are obtained by extrusion.
10. A granule obtainable by a process according to any one of the preceding claims.
11. A crop protection composition comprising a granule according to claim 10.
12. Use of a composition according to claim 11 for the prevention, suppression, or treatment of infectious diseases in agriculture.
13. Use of a composition according to claim 11 for the prevention, suppression, or treatment of fire blight.
PCT/EP2002/008076 2001-07-19 2002-07-17 Streptomycin-containing granules and process for the preparation thereof WO2003007712A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP01202777 2001-07-19
EP01202777.7 2001-07-19

Publications (1)

Publication Number Publication Date
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120107422A1 (en) * 2009-07-10 2012-05-03 Chevita Tierarzneimittel Gmbh Compositions and method for preventing and treating fire blight

Citations (7)

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Publication number Priority date Publication date Assignee Title
GB788668A (en) * 1954-06-14 1958-01-08 Pfizer & Co C Improvements in or relating to antibiotic compositions for treating plants
JPS5212925A (en) * 1975-07-19 1977-01-31 Microbial Chem Res Found A plant disease controlling agent
JPS55153706A (en) * 1979-05-17 1980-11-29 Hokko Chem Ind Co Ltd Fungicide for agriculture and gardening
JPS60224608A (en) * 1984-04-23 1985-11-09 Takeda Chem Ind Ltd Stable fungicidal composition for agriculture and horticulture
JPS6299356A (en) * 1985-10-25 1987-05-08 Nippon Niyuukazai Kk Granular wettable powder composition
WO1989000079A1 (en) * 1987-07-01 1989-01-12 Ici Australia Operations Proprietary Limited Water dispersible granules
JPH09124406A (en) * 1995-11-06 1997-05-13 Takeda Chem Ind Ltd Granulated water dispersible powder

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB788668A (en) * 1954-06-14 1958-01-08 Pfizer & Co C Improvements in or relating to antibiotic compositions for treating plants
JPS5212925A (en) * 1975-07-19 1977-01-31 Microbial Chem Res Found A plant disease controlling agent
JPS55153706A (en) * 1979-05-17 1980-11-29 Hokko Chem Ind Co Ltd Fungicide for agriculture and gardening
JPS60224608A (en) * 1984-04-23 1985-11-09 Takeda Chem Ind Ltd Stable fungicidal composition for agriculture and horticulture
JPS6299356A (en) * 1985-10-25 1987-05-08 Nippon Niyuukazai Kk Granular wettable powder composition
WO1989000079A1 (en) * 1987-07-01 1989-01-12 Ici Australia Operations Proprietary Limited Water dispersible granules
JPH09124406A (en) * 1995-11-06 1997-05-13 Takeda Chem Ind Ltd Granulated water dispersible powder

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Title
DATABASE WPI Derwent World Patents Index; AN 1977-18789Y, XP002219598, "Agricultural germicide contg. negamycin (salt)-used against e.g. Pseudomonas lachrymans, glumae, mori and solancearum, and streptomyces scables" *
DATABASE WPI Derwent World Patents Index; AN 1981-08481D, XP002219597, "Agricultural fungicide-contains active mixt. of kasugamycin (salt) with polyoxin Gp. antibiotic salt." *
DATABASE WPI Derwent World Patents Index; AN 1985-320774, XP002219599, "Stabilised agricultural fungicide compsn.-contg. valinomycin, mineral carrier and preservative e.g. benzoic acid" *
DATABASE WPI Derwent World Patents Index; AN 1987-167067, XP002219594, "Granular wettable agrochemical composition-contains alkyl di:phenyl ether di:sulphonic acid." *
DATABASE WPI Derwent World Patents Index; AN 1994-190416, XP002219596, "Antibiotic tablets prodn.-by drying and simultaneous granulation, in fluidised layer, of inert fillers, sprayed with aq. soln. of antibiotic and starch" *
DATABASE WPI Derwent World Patents Index; AN 1997-316417, XP002219595, "Granular water dispersible agent-comprises chemical active agent and metal oxide e.g. aluminium oxide, and may additionally include anionic or non-ionic surfactant." *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120107422A1 (en) * 2009-07-10 2012-05-03 Chevita Tierarzneimittel Gmbh Compositions and method for preventing and treating fire blight
US9149043B2 (en) * 2009-07-10 2015-10-06 Ulf Abele Compositions and method for preventing and treating fire blight

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