WO2015123745A1 - Method for nanoencapsulating active principles in an inverse double emulsion and resulting products - Google Patents

Method for nanoencapsulating active principles in an inverse double emulsion and resulting products Download PDF

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Publication number
WO2015123745A1
WO2015123745A1 PCT/BR2015/000018 BR2015000018W WO2015123745A1 WO 2015123745 A1 WO2015123745 A1 WO 2015123745A1 BR 2015000018 W BR2015000018 W BR 2015000018W WO 2015123745 A1 WO2015123745 A1 WO 2015123745A1
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emulsion
phase
water
assets
inverse
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French (fr)
Portuguese (pt)
Inventor
Adriano Marim de OLIVEIRA
Renato Rosafa GAVIOLI
Natalia Neto Pereira CERIZE
Maria Helena Ambrosio ZANIN
Kleber Lanigra GUIMARÃES
Lucilene Betega de PAIVA
Vitorio Giovanni Zanetti Ferraz
Moacir de MANCILHA
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IHARABRAS SA INDUSTRIAS QUIMICAS
Instituto de Pesquisa Tecnologicas do Estado Sao Paulo S/A (IPT)
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IHARABRAS SA INDUSTRIAS QUIMICAS
Instituto de Pesquisa Tecnologicas do Estado Sao Paulo S/A (IPT)
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    • 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
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/11—Encapsulated compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/73—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/10—General cosmetic use
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41—Particular ingredients further characterized by their size
    • A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
    • 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
    • A61K9/5192—Processes

Definitions

  • the invention pertaining to the employment sector of pre-treated encapsulated organic ingredients for use in asset preparations applied to agrochemicals, pharmaceuticals, cosmetics, veterinary, food, paper, paints, adhesives, oil and gas, construction, textile , consists of a nanoencapsulated generation method based on the three-phase double emulsification, comprised of an active-rich inner phase to be encapsulated and a low water miscibility oil, an intermediate phase consisting of the encapsulant material dissolved in water and a phase. external compound composed of emulsifier dissolved in silicone.
  • the formation of the nano-encapsulated occurs after distillation of the aqueous intermediate phase and precipitation of the encapsulating material under the internal oily phase containing the active.
  • This method is capable of generating nanostructured shell-core special physical forms (nanoparticles) containing an oily core and a semipermeable polymeric shell dispersed in a silophilic hydrophobic phase, allowing the release of the active substance from within by diffusion or rapid release. by the breaking of the shell by the action of mechanical stress or solubilization.
  • the "NANOENCAPSULATION METHOD OF DUAL INVERSE EMULSION ASSETS AND RESULTANT PRODUCTS” presents a method for obtaining nanoencapsulated assets, generated as a dispersion in the silophilic phase, by means of a double phase nanoemulsion process followed by extraction of intermediate phase water by distillation and formation of nanocapsules.
  • This method presents as the use of a double inverse emulsion so that the active - hydrophobic or partially hydrophilic - is encapsulated in low water solubility oil by a hydrophilic polymer, and the resulting nano-encapsulated product is suspended in a medium. silophilic. 04.
  • the method comprises the execution of five consecutive processing phases, which allow the generation of nanoencapsulated, a) solubilization of the assets to be nanoencapsulated; b) pre-emulsifying a phase containing the assets solubilized in an immiscible or water-miscible solvent in a saturated aqueous solvent phase and containing encapsulant material; c) emulsifying this resulting preemulsion into a silophilic oil containing emulsifiers; d) nanoemulsification of this double emulsion; e) distillation for extraction of water from the intermediate phase and formation of nanocapsules.
  • the generated products are presented as a colloidal dispersion in silophilic medium.
  • the "Nanoencapsulation Method of Double Reverse Emulsion Assets and Resulting Products” enables different types of nanoencapsulated to be obtained and may be as high as 10% by mass in the final product, allowing a range of applications in various sectors of industry, such as pharmaceutical, cosmetic, veterinary, food, agrochemical, paper, inks, adhesives, oil and gas, construction, textile, among others, for the possibility of developing different compositions of nanoencapsulated containing assets that have incomplete solubility or partial in aqueous medium.
  • Leaching or degradation phenomena further reduce any possible residual effect of the product, making consecutive applications necessary in situations where use should be continued. Consecutive applications result in increased costs associated with product use, possible occupational risk due to operator exposure to the products, and increased amount of assets in the application environment.
  • Asset encapsulation techniques have been used to protect these assets from phenomena such as those described, offering advantages when using a particular asset, such as its controlled release to the medium by diffusion, or rapid release through disruption. of the shell due to the action of mechanical stress. This effect allows for fewer product applications containing the asset and greater security for users.
  • the particles showed improved resistance to thermal degradation and ultraviolet radiation, with ultraviolet degradation more than 10 times lower than free active.
  • Nanocapsulated production can be based on various methods such as solvent evaporation, emulsification and solvent diffusion, salting out, supercritical fluids, preformed polymer dispersion, polymerization of monomers, and nanocapsule production methods. from the gelling of ionic polymers.
  • the nanocapsulation process by the solvent evaporation method was the first method developed for the preparation of polymeric nanoparticles from preformed polymers.
  • polymeric solutions containing the active ingredient are prepared in volatile solvents and then simple emulsions are formed, which are converted to nanoparticle suspensions upon evaporation of the solvent.
  • This technique is the most used in the preparation of polymeric nanoparticles according to the current literature.
  • ES 2 194 590 A1 (ES2194590 A1, Biodegradable Microspheres with Extended Release and Preparation Procedure, FERRET, AND, ASIN, ME.GARC ⁇ A, J., TARIN, P., AROLA, R., RUTLL ⁇ N, M -, PÉREZ, A., 2001) a double w / o / w emulsion was used from a method in which the active was dissolved in the aqueous internal phase and it was emulsified into a hydrocarbon containing a dissolved polymer, and this emulsion was again emulsified into an aqueous phase containing emulsifiers. The organic solvent was then evaporated so that microparticles could be obtained.
  • the formed microcapsules encapsulate hydrophilic actives with the use of water insoluble polymer.
  • FR 2808703 A1 (FR2808703 A1 Proceeds from the preparation of a double monodisperse emulsion, FERNANDO, L. C, PHILIPPE, G., JAQUES, BJM, 2000) describes a method for obtaining a monodisperse double water emulsion. in oil in water (w / o / w) by mixing an aqueous phase into an oil phase followed by dilution in oil, and incorporating this pre-emulsion into a second aqueous phase by high pressure homogenization.
  • the "Nanoencapsulation Method of Double Reverse Emulsion Assets and Resulting Products” comprises a method for the nanoencapsulation of poorly water soluble assets. Encapsulation is achieved by dissolving the active in a water-immiscible or low-miscible solvent with a boiling point greater than water, which is pre-emulsified in an aqueous solution containing hydrophilic polymers. This preemulsion is again emulsified in a lipophilic oil, giving rise to a double inverse emulsion. The double inverse emulsion is further subjected to high pressure homogenization, and the resulting nanoemulsion is subjected to distillation to extract water from the intermediate phase.
  • the method makes it possible to obtain a suspension of core-shell nanoparticles containing poorly water-soluble active material dissolved in a core solvent and shell composed of solid hydrophilic polymer.
  • the external phase of the suspension is a hydrophobic silophilic type oil.
  • Figure 1 shows the size distribution curves for the 3.7% active sample, with the curves indicating triplicate measurements of the same sample.
  • Figure 3 - shows the size distribution curves for the 2.2% active sample, with the curves indicating triplicate measurements of the same sample.
  • Figure 4 Photomicrograph of nanocapsulated with 2.2% active nanometer order 027.
  • Figure 5 shows the size distribution curves for the 8.0% active sample, with the curves indicating triplicate measurements of the same sample.
  • Figure 7 - shows the size distribution curves for the 3.4% active sample, with the curves indicating triplicate measurements of the same sample.
  • Figure 9 - shows the size distribution curves for the 3.2% active sample, with the curves indicating triplicate measurements of the same sample.
  • the "Method of NANOENCAPSULATION OF INVERSE DUPLAEMULSION ASSETS AND RESULTING PRODUCTS" is a form of obtaining nanoencapsulated by double inverse emulsification followed by extraction of the intermediate phase by distillation.
  • This method is comprised of the execution of five consecutive processing steps that allows the generation of nanoencapsulates. These steps are: a) solubilization of the assets to be nanocapsulated; b) pre-emulsifying a phase containing the assets solubilized in a water immiscible or poorly miscible solvent in a saturated aqueous phase of the solvent and containing encapsulating material; c) emulsifying this resulting preemulsion into a silophilic oil containing emutants; d) nanoemulsification of this double emulsion; and e) distillation for water extraction from the intermediate phase and formation of nanocapsules.
  • step a) or organic phase is carried out by mechanical or magnetic stirring of the solvent and the actives to be nanocapsulated. Stirring is performed until complete solubilization of the assets at a temperature ranging from 5 to 90 ° C, preferably 23 ° C, with stirring from 5 to 3,000 rpm, preferably 400 rpm, at ambient pressure.
  • the solvent used should be immiscible or poorly water miscible and boiling higher than water, preferably 205 ° C.
  • the assets must be hydrophobic or partially hydrophilic or combinations of them.
  • the present invention may provide formulations containing chemical or biological active ingredient (s) acting in the desired area and may be at least one fungicide, insecticide, insecticide synergist, larvicide, arthropod repellent, mating disruptor, pheromone, acaricide, algaecide, virucide, nematicide, molluscicide, herbicide, herbicide protector, growth regulator, growth promoter, fruiting stimulant, flower and / or fruit preservative, early flower fall prevention ingredient and / or fruit, bird repellent, avicide, rodenticide, mammal repellent, herbivorism inhibitor, chemical sterilizer, but not limited to or mixture thereof, preferably active ingredients belonging to that group with a water solubility of less than 100 g / l.
  • the encapsulating material is natural or synthetic polymer such as polysaccharide polymers, animal or vegetable protein, chitosan, gums (gum arabic, xanthan gum, guar gum, carrageenan gum, cashew gum, tara gum, tragacanth gum). , Karaya gum, gati gum), cellulose derivatives (carboxymethyl cellulose, carboxyethyl cellulose, etc.), polyvinylpyrrolidone, polyacrylates, polyacrylamides, polyvinylcaprolactams, and mixtures thereof, preferably polysaccharides such as starch.
  • natural or synthetic polymer such as polysaccharide polymers, animal or vegetable protein, chitosan, gums (gum arabic, xanthan gum, guar gum, carrageenan gum, cashew gum, tara gum, tragacanth gum). , Karaya gum, gati gum), cellulose derivatives (carboxymethyl cellulose, carboxyethyl
  • the polymers are used dissolved in water in a concentration of 4% to 35% by weight, preferably 22%, the water used being saturated with the solvent that makes up the organic phase prior to solubilization of the polymers and the solvents being long chain esters, the aromatics , and hydrocarbons.
  • an organic or inorganic salt added at concentrations ranging from 0.1 to 10% by weight, preferably 1% w / w, which acts as an electrolyte for co-stabilization during the second emulsification step.
  • water soluble salts preferably mono or bivalent chlorides.
  • the second step (step b) that composes the method is the preemulsification of the two solutions (solvent active solution and polymer in water solution) described above. Preemulsification is carried out by mechanical or magnetic stirring of the organic phase in the aqueous phase at a minimum speed of 100 rpm, preferably 1,000 rpm, at a temperature ranging from 5 to 90 ° C, preferably 23 ° C and ambient pressure.
  • the ratio of organic phase to aqueous phase may vary from 1: 1 to 1: 50 by mass, since for high cost pharmaceutical actives the well-diluted system, preferably 1: 2 by mass may be used.
  • the third step (step c) is the emulsification of the preemulsion generated in step b) into a hydrophobic dilute emulsifier of the silophilic type, using emulsifiers compatible with the silophilic phase, for example, silicone emulsifiers or silicon-modified silicone. polyoxydeethylene.
  • This emulsification is performed by mechanical agitation of the pre-emulsion in the silophilic phase at speeds ranging from 100 to 30,000 rpm (which for high cost pharmaceutical actives can be used well diluted system), preferably 1,000 rpm; temperature ranging from 5 to 90 ° C, preferably 23 ° C and ambient pressure, and the pre-emulsion ratio in the silophilic phase may range from 2: 1 to 1: 20 by mass (for high cost pharmaceutical actives use the well-diluted system), preferably 1: 1 by mass.
  • the fourth step (step d) is the nanoemulsification of the double emulsion resulting from step c).
  • This nanoemulsification is carried out with the aid of high pressure homogenization, using a number of cycles from a minimum of 1 to that required to achieve the desired particle size, generally less than 20 cycles, preferably 5 cycles.
  • the pressure used in the process should be a minimum of 50 bar and a maximum of 2,000 bar, preferably 1000 bar.
  • the temperature employed in the process ranges from 10 to 100 ° C, preferably ambient.
  • step e is the extraction of water from the intermediate phase (external phase of the emulsion generated in step b) by distillation under reduced pressure, elevated temperature and moderate agitation. Distillation is conducted at a pressure of less than 760 mmHg, preferably 140 mmHg, and a temperature between 23 ° C and 90 ° C, preferably 50 ° C, for as long as necessary to remove water from the system, which may take from 10 minutes to 20 minutes. hours, usually 3 hours. ⁇
  • the obtained material was mixed with 100 g of a silica oil phase composed of silicone oil, Xiameter PMX-200 100 OffDow Corning), containing 10% emulsifier, SF-1540® (Momentivé), with the aid of stirrer at 000 ° C. rpm This emulsion was then subjected to 5 cycles of high pressure emulsification at 1000 bar pressure.
  • a silica oil phase composed of silicone oil, Xiameter PMX-200 100 OffDow Corning
  • 10% emulsifier SF-1540® (Momentivé)
  • the nanoemulsion resulting from this operation was subjected to distillation in a jacketed glass reactor, mechanically agitated, with water circulation at 50 ° C at 110 mmHg pressure for 7 hours.
  • the obtained material was mixed to 100 g of a siliaphilic phase composed of silicone oil, Xiameter PMX-200 100 CS® (Dow Corning J. containing 10% specific emulsifier SF-1540® (Momentive), with the aid of stirrer at 1000 rpm This emulsion was then subjected to 5 cycles of high pressure emulsification at 1000 bar pressure.
  • the nanoemulsion resulting from this operation was subjected to distillation in a jacketed glass reactor, mechanically agitated, with water circulation at 70 ° C, at a pressure of 170 mmHg, for 5 hours.
  • the resulting nanoencapsulated was subjected to particle size analysis by dynamic scattering technique, morphological scanning electron microscopy and total active content by high performance liquid chromatography.
  • Figure 3 shows the size distribution curve for the nanocapsules obtained, averaging around 350nm.
  • Figure 4 shows the morphology of the obtained particles.
  • the nanoemulsion resulting from this operation was subjected to distillation in a jacketed glass reactor, mechanically agitated, with water circulation at 35 ° C at a pressure of 95mmHg for 9 hours.
  • the resulting nanoencapsulated was subjected to particle size analysis by dynamic scattering technique, scanning electron microscopic morphology and total active content by high performance liquid chromatography.
  • Figure 5 shows the size distribution curve for the obtained nanocapsules, averaging around 300nm.
  • Figure 6 shows the morphology of the obtained particles.
  • the material obtained was mixed to 100 g of a silophilic phase composed of silicone oil, Xiameter PMX-200 100 CS® (Dow Corning). Containing 10% specific emulsifier SF-1540® (Momentive), with the aid of stirrer at 1000 rpm. This emulsion was then subjected to five cycles of high pressure emulsification at a pressure of 000 bar.
  • the nanoemulsion resulting from this operation was subjected to distillation in a jacketed glass reactor, mechanically agitated, with water circulation at 35 ° C, at a pressure of 235 mmHg, for 9 hours.
  • the resulting nanoencapsulated was subjected to particle size analysis by dynamic, morphological scanning electron microscopy and total active content by high performance liquid chromatography.
  • Figure 7 shows the size distribution curve for the obtained nanocapsules, averaging around 250 nm.
  • Figure 8 shows the morphology of the obtained particles.
  • the material obtained was mixed to 100 g of a silica oil phase composed of silicone oil, Xiameter PMX-200 100 CS® (Dow Corning), containing 10% specific emulsifier SF-1540® (Momentive), with the aid of stirrer at 1000 rpm. This emulsion was then subjected to five cycles of high pressure emulsification at 1000 bar pressure.
  • the nanoemulsion resulting from this operation was subjected to distillation in a 500 ml jacketed glass reactor with mechanical stirring, with water circulation at 70 ° C, at a pressure of 235 mmHg, for 5 hours.
  • the resulting nanoencapsulated was subjected to particle size analysis by dynamic scattering technique, scanning electron microscopy morphology and total active content by high performance liquid chromatography.
  • Figure 9 shows the size distribution curve for the obtained nanocapsules, averaging around 250 nm, and Figure 10 shows the morphology of the particles obtained.

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Abstract

The "Method for nanoencapsulating active principles in an inverse double emulsion and resulting products" describes a method for producing nanoencapsulated active principles, which are generated as a dispersion in a silicophilic phase by means of a process of inverse-phase double nanoemulsion, followed by extraction of water from the intermediate phase by distillation, and nanocapsule formation. Said method describes the use of an inverse double emulsion, such that the hydrophobic or partially hydrophilic active principle is encapsulated in oil with low solubility in water by means of a hydrophilic polymer, and the resulting nanoencapsulated product is in the form of a suspension in a silicophilic medium. Said method comprises carrying out five consecutive processing steps to generate the nanocapsules, consisting of a) solubilizing the active principles to be nanoencapsulated; b) pre-emulsifying a phase containing the active principles solubilized in a solvent that is immiscible or only slightly miscible in water in a saturated aqueous phase of the solvent, and containing encapsulating material; c) emulsifying this resulting pre-emulsion in a silicophilic oil containing emulsifiers; d) nanoemulsifying this double emulsion, and e) distilling for extraction of water from the intermediate phase and nanocapsule formation. The products generated are in the form of a colloidal dispersion in silicophilic medium. The "Method for nanoencapsulating active principles in an inverse double emulsion and resulting products" allows different types of nanocapsules to be produced, wherein the active principle content can be over 10% by weight in the final product, allowing a range of uses in various industry sectors, such as the pharmaceutical, cosmetic, veterinary, food, agrochemical, paper, paint, adhesive, petroleum and gas, construction, and textile industries, inter alia, due to the possibility of producing different nanocapsule compositions containing active principles that are incompletely or only partially soluble in an aqueous medium.

Description

MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA E PRODUTOS RESULTANTES NANOENCAPSULATION METHOD OF DOUBLE INVERSE EMULSION ASSETS AND RESULTING PRODUCTS

CA PO DE ATUAÇÃO ACT OF OPERATION

01. A invenção, pertencente ao setor de emprego de ingredientes orgânicos encapsulados pré-tratados para uso em preparações de ativos aplicados a produtos agroquímicos, farmacêuticos, cosméticos, veterinários, alimentícios, papel, tintas, adesivos, petróleo e gás, construção civil, têxtil, consiste em um método de geração de nanoencapsulados baseado na emulsificação dupla de três fases, compreendidas por uma fase interna rica em âtivo a ser encapsulado e um óleo de baixa miscibilidade em água, uma fase intermediária constituída pelo material encapsulante dissolvido em água e uma fase externa composta por emulsificante dissolvido em silicone.  01. The invention, pertaining to the employment sector of pre-treated encapsulated organic ingredients for use in asset preparations applied to agrochemicals, pharmaceuticals, cosmetics, veterinary, food, paper, paints, adhesives, oil and gas, construction, textile , consists of a nanoencapsulated generation method based on the three-phase double emulsification, comprised of an active-rich inner phase to be encapsulated and a low water miscibility oil, an intermediate phase consisting of the encapsulant material dissolved in water and a phase. external compound composed of emulsifier dissolved in silicone.

02. A formação do nanoencapulado ocorre após a destilação da fase intermediaria aquosa e a precipitação do material encapsulante sob a fase interna oleosa contendo o ativo. Este método é capaz de gerar formas físicas especiais nanoestruturadas (nanopartículas) do tipo casca-núcleo, contendo um núcleo oleoso e uma casca polimérica semipermeável dispersa em uma fase hidrofóbica do tipo silofílica, permitindo a liberação do ativo do seu interior por difusão ou liberação rápida por melo do rompimento da casca pela ação de esforço mecânico ou solubilização.  02. The formation of the nano-encapsulated occurs after distillation of the aqueous intermediate phase and precipitation of the encapsulating material under the internal oily phase containing the active. This method is capable of generating nanostructured shell-core special physical forms (nanoparticles) containing an oily core and a semipermeable polymeric shell dispersed in a silophilic hydrophobic phase, allowing the release of the active substance from within by diffusion or rapid release. by the breaking of the shell by the action of mechanical stress or solubilization.

RESUMO DA INVENÇÃO  SUMMARY OF THE INVENTION

03. O "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA E PRODUTOS RESULTANTES" apresenta um método de obtenção de ativos nanoencapsulados, gerados na forma de uma dispersão em fase silofílica, por meio de um processo de nanoemulsão dupla em fase inversa, seguida de extração de água da fase intermediária por destilação e formação das nanocápsulas. Este método apresenta como o uso de uma dupla emulsão inversa, de modo que o ativo - hidrofóbico ou parcialmente hidrofílico - seja encapsulado em óleo de baixa solubilidade em água por um polímero hidrofílico, e o produto nanoencapulado resultante encontre-se em suspensão em um meio silofílico. 04. O método compreende a execução de cinco fases de processamento consecutivas, que permitem a geração dos nanoencapsulados, sendo a) solubilização dos ativos a ser nanoencapsulados; b) pré-emulsificação de uma fase contendo os ativos solubilizados em um solvente imiscível ou pouco miscível em água em uma fase aquosa saturada do solvente e contendo material encapsulânte; c) emulsifícação desta pré-emulsão resultante em um óleo silofílico contendo emulsificantes; d) nanoemulsificação desta dupla emulsão e e) destilação para extração de água da fase intermediária e formação das nanocápsulas. Os produtos gerados se apresentam na forma de uma dispersão coloidal em meio silofílico. 03. The "NANOENCAPSULATION METHOD OF DUAL INVERSE EMULSION ASSETS AND RESULTANT PRODUCTS" presents a method for obtaining nanoencapsulated assets, generated as a dispersion in the silophilic phase, by means of a double phase nanoemulsion process followed by extraction of intermediate phase water by distillation and formation of nanocapsules. This method presents as the use of a double inverse emulsion so that the active - hydrophobic or partially hydrophilic - is encapsulated in low water solubility oil by a hydrophilic polymer, and the resulting nano-encapsulated product is suspended in a medium. silophilic. 04. The method comprises the execution of five consecutive processing phases, which allow the generation of nanoencapsulated, a) solubilization of the assets to be nanoencapsulated; b) pre-emulsifying a phase containing the assets solubilized in an immiscible or water-miscible solvent in a saturated aqueous solvent phase and containing encapsulant material; c) emulsifying this resulting preemulsion into a silophilic oil containing emulsifiers; d) nanoemulsification of this double emulsion; e) distillation for extraction of water from the intermediate phase and formation of nanocapsules. The generated products are presented as a colloidal dispersion in silophilic medium.

05. O "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA E PRODUTOS RESULTANTES" permite a obtenção de diferentes tipos de nanoencapsulados e em teores de ativos que podem passar de 10% em massa no produto final, o que permite um gama de aplicações em diversos setores da indústria, tais como farmacêutica, cosmética, veterinária, alimentícia, agroquímica, papel, tintas, adesivos, petróleo e gás, construção civil, têxtil, entre outros, pela possibilidade de desenvolver diferentes composições de nanoencapsulados contendo ativos que apresentem solubilidade incompleta ou parcial em meio aquoso.  05. The "Nanoencapsulation Method of Double Reverse Emulsion Assets and Resulting Products" enables different types of nanoencapsulated to be obtained and may be as high as 10% by mass in the final product, allowing a range of applications in various sectors of industry, such as pharmaceutical, cosmetic, veterinary, food, agrochemical, paper, inks, adhesives, oil and gas, construction, textile, among others, for the possibility of developing different compositions of nanoencapsulated containing assets that have incomplete solubility or partial in aqueous medium.

ESTADO DA TÉCNICA  TECHNICAL STATE

06. Diversos são os produtos baseados em suspensões aquosas de ativos pouco solúveis em água para aplicações diversas, que podem ser utilizados de diversos modos como, por exemplo, através de diluição e pulverização.  06. Several are products based on aqueous suspensions of poorly water-soluble actives for various applications which can be used in various ways such as dilution and spraying.

07. Quando aplicado em um ambiente externo, um produto deste tipo pode sofrer lixiviação em decorrência de chuvas, devido ã solubilidade parcial em água, por conseguinte o ativo é removido rapidamente da área de interesse de aplicação, tendo sua eficácia diminuída e fazendo necessárias novas aplicações do produto com consequente aumento de custo. Ainda, todo o ativo extraído pela água de chuva pode ser carregado para outros ambientes ou sistemas nos quais sua presença pode ser prejudicial. 08. Ainda após a aplicação, uma vez evaporada a água que compõe a suspensão tal qual a descrita, o produto resultante é o ativo puro em geral na forma de cristal, que pode ser suscetível a diversos fenómenos passíveis de mudar suas propriedades com redução dá eficácia do produto, tais como exposição ao calor, à radiação ultravioleta, intempéries, variação de pH, oxidação, ventos, contaminação química por poluentes, dentre diversos outros fenómenos. 07. When applied in an outdoor environment, a product of this type may be leached as a result of rainfall due to partial solubility in water, therefore the asset is rapidly removed from the area of application, its effectiveness diminished and new requirements are required. product applications with consequent cost increases. Also, any assets extracted by rainwater may be carried to other environments or systems where their presence may be detrimental. 08. Still after application, once the water in the suspension is evaporated as described above, the resulting product is the pure active generally in crystal form, which may be susceptible to various phenomena which may change their properties with reduction. product efficacy, such as exposure to heat, ultraviolet radiation, weather, pH variation, oxidation, wind, chemical contamination by pollutants, among many other phenomena.

09. Lixiviação ou fenómenos de degradação ainda reduzem qualquer possível efeito residual do produto, fazendo necessárias aplicações consecutivas em situações nas quais o uso deva ser continuado. Aplicações consecutivas acarretam em aumento dos custos associados ao uso do produto, possível risco ocupacional devido à exposição de operadores aos produtos, e aumento da quantidade de ativo no ambiente de aplicação.  09. Leaching or degradation phenomena further reduce any possible residual effect of the product, making consecutive applications necessary in situations where use should be continued. Consecutive applications result in increased costs associated with product use, possible occupational risk due to operator exposure to the products, and increased amount of assets in the application environment.

010. Técnicas de encapsulação de ativos têm sido utilizadas com o objetivo de proteger estes ativos de fenómenos como os descritos, oferecendo vantagens quando do uso de um determinado ativo, como sua liberação controlada para o meio por difusão, ou liberação rápida por meio do rompimento da casca devido à ação do esforço mecânico. Este efeito permite uma menor quantidade de aplicações do produto contendo o ativo e maior segurança para os usuários.  010. Asset encapsulation techniques have been used to protect these assets from phenomena such as those described, offering advantages when using a particular asset, such as its controlled release to the medium by diffusion, or rapid release through disruption. of the shell due to the action of mechanical stress. This effect allows for fewer product applications containing the asset and greater security for users.

011. Cao et a/(CAO Y, HUANG L, CHEN J, LIANG J, LONG S, LU Y. Development of a Controlled Release Formulation Based on a Starch Matríx 011. Cao et al / (CAO Y, HUANG L, CHEN J, LIANG J, LONG S, LU Y. Development of a Controlled Release Formulation Based on a Starch Matrix

System. International Journal of Pharmaceutics 2005; 298 108-116) produziram microcápsulas com diâmetro entre 2 e 20 pm contendo acetamiprid encapsulado - um inseticida sensível a altas temperaturas e pouco solúvel em água - utilizando amido como matriz contendo ureia e borato de sódio como aditivos. As partículas apresentaram melhoria na resistência à degradação térmica e à radiação ultravioleta, com degradação por ultravioleta mais que 10 vezes menor em relação ao ativo livre. System International Journal of Pharmaceutics 2005; 298 108-116) produced microcapsules 2 to 20 µm in diameter containing encapsulated acetamiprid - a high temperature sensitive insecticide that is poorly soluble in water - using starch as a matrix containing urea and sodium borate as additives. The particles showed improved resistance to thermal degradation and ultraviolet radiation, with ultraviolet degradation more than 10 times lower than free active.

012. Em outro trabalho com acetamiprid, Takei et a/(TAKEI T, Yoshida M, Hatate Y, Shiomori K, KIYOYAMA S. Preparation of Po!ylactide/Poly(C- Caprolactone) Microspheres Enclosing Acetamipridand Evaluation of Release Behavior Polymer Bulletin 2008; 61 391-397) produziram micropartículas utilizando uma mistura de poli(ácido iático) e poli(E-caprolactona) como agente de encapsulamento. Foram formadas microesferas com diâmetro de 20 a120 pm, com capacidade de liberação controlada do inseticida. 012. In another work with acetamiprid, Takei et al / (TAKEI T, Yoshida M, Hatate Y, Shiomori K, KIYOYAMA S. Preparation of Po-ylactide / Poly (C-Caprolactone) Microspheres Enclosing Acetamipridand Evaluation of Release Behavior Polymer Bulletin 2008 ; 61 391-397) produced microparticles using a mixture of poly (iactic acid) and poly (E-caprolactone) as encapsulating agent. Microspheres were formed with diameter from 20 to 120 pm, with controlled release capacity of the insecticide.

013. A produção de nanoencapsulados pode ser baseada em diversos métodos, como evaporação do solvente, emulsificação e difusão em solvente, "Salting out", fluídos supercríticos, dispersão de polímero pré-formado, polimerização de monômeros, além dos métodos de produção de nanocápsuias a partir da gelificação de polímeros iónicos.  013. Nanocapsulated production can be based on various methods such as solvent evaporation, emulsification and solvent diffusion, salting out, supercritical fluids, preformed polymer dispersion, polymerization of monomers, and nanocapsule production methods. from the gelling of ionic polymers.

014. O processo de nanoencapsulação através do método de evaporação de solvente foi o primeiro método desenvolvido para a preparação de nanopartículas polimérícas a partir de polímeros pré-formados. Neste método, soluções polimérícas contendo o princípio ativo são preparadas em solventes voláteis e então são formadas emulsões simples, que são convertidas em suspensões de nanopartículas mediante a evaporação do solvente. Esta técnica é a mais utilizada na preparação de nanopartículas polimérícas de acordo com a literatura atual.  014. The nanocapsulation process by the solvent evaporation method was the first method developed for the preparation of polymeric nanoparticles from preformed polymers. In this method, polymeric solutions containing the active ingredient are prepared in volatile solvents and then simple emulsions are formed, which are converted to nanoparticle suspensions upon evaporation of the solvent. This technique is the most used in the preparation of polymeric nanoparticles according to the current literature.

015. Emulsões múltiplas de água em óleo em água (a/o/a) foram estudadas por Schurchef ai (SCHUCH, A., DEITERS, P., Henne, J., Kõhler, K., SCHUCHMANN, H. P.. Production of W/O/W (water-in-oil-in-water) multiple emulsions: droplet breakup and release of water, Journal of Colloidand Interface Science, Volume 402, 15 July 2013, Pags. 157-164), inclusive alterações no comportamento reológico da emulsão em função do conteúdo de fase interna e os mecanismos de liberação de água por coalescência. Por meio deste mecanismo, a água é liberada da fase interna para a fase externa, e não da fase intermediária para fora do sistema. Neste estudo, no entanto, não foi utilizado nenhum tipo de ativo, tampouco foram formadas nanocápsuias - o material apresentou-se na escala micrométrica.  015. Multiple water-to-water (w / o / w) emulsions were studied by Schurchefi (SCHUCH, A., DEITERS, P., Henne, J., Köhler, K., SCHUCHMANN, HP. Production of W / O / W (water-in-oil-in-water) multiple emulsions: breakup droplet and release of water, Journal of Colloidand Interface Science, Volume 402, 15 July 2013, Pages 157-164), including changes in rheological behavior of emulsion as a function of internal phase content and mechanisms of water release by coalescence. Through this mechanism, water is released from the internal to the external phase, not from the intermediate phase out of the system. In this study, however, no type of asset was used, nor were nanocapsules formed - the material was on the micrometer scale.

016. No documento ES 2 194 590 A1 (ES2194590 Al, Microesferas biodegradables com iiberación prolongada y su procedimiento de preparación, FERRET, E, ASÍN, M. E..GARCÍA, J., TARÍN, P., AROLA, R., RUTLLÁN, M-, PÉREZ, A., 2001) foi utilizada uma dupla emulsão a/o/a, a partir de um método no qual o ativo foi dissolvido na fase interna aquosa, e esta foi emulsionada em um hidrocarboneto contendo um polímero dissolvido, sendo que esta emulsão foi novamente emulsionada em uma fase aquosa contendo emulsificantes. O solvente orgânico foi então evaporado para que pudessem ser obtidas micropartículas. As microcápsulas formadas encapsulam ativos hidrofílicos com o uso de polímero insolúvel em água. 016. In ES 2 194 590 A1 (ES2194590 A1, Biodegradable Microspheres with Extended Release and Preparation Procedure, FERRET, AND, ASIN, ME.GARCÍA, J., TARIN, P., AROLA, R., RUTLLÁN, M -, PÉREZ, A., 2001) a double w / o / w emulsion was used from a method in which the active was dissolved in the aqueous internal phase and it was emulsified into a hydrocarbon containing a dissolved polymer, and this emulsion was again emulsified into an aqueous phase containing emulsifiers. The organic solvent was then evaporated so that microparticles could be obtained. The formed microcapsules encapsulate hydrophilic actives with the use of water insoluble polymer.

017. O documento FR 2808703 A1 (FR2808703 A1 Procede de preparation d'une emulsion double monodisperse, FERNANDO, L. C, PHILIPPE, G., JAQUES, B. J. M., 2000) descreve um método para a obtenção de uma emulsão dupla monodispersa de água em óleo em água (a/o/a) por meio da mistura de uma fase aquosa em uma fase oleosa seguida de diluição em óleo, e a incorporação desta pré-emulsão em uma segunda fase aquosa mediante homogeneização de alta pressão.  017. FR 2808703 A1 (FR2808703 A1 Proceeds from the preparation of a double monodisperse emulsion, FERNANDO, L. C, PHILIPPE, G., JAQUES, BJM, 2000) describes a method for obtaining a monodisperse double water emulsion. in oil in water (w / o / w) by mixing an aqueous phase into an oil phase followed by dilution in oil, and incorporating this pre-emulsion into a second aqueous phase by high pressure homogenization.

018. O uso de emulsão inversa para a nanoencapsulação de ativos hidrofílicos é objeto do pedido de patente de invenção n° P1100 959-6 (PI 1001959-6; OLIVEIRA, M. A., TEDESCO, A. C, RÉ, M. I.; CERIZE, N. N. P.; Nanocarreadores coloidais para ativos hidrofílicos e processo de produção, 2010). No método, uma solução aquosa de ativo hidrofílico e polímero foi nanoemulsionada em um óleo hidrofóbico, e a emulsão resultante foi submetida à destilação para a remoção da água e formação de nanopartículas. As nanopartículas formadas não se apresentam, no entanto, como estruturas do tipo casca-núcleo.  018. The use of inverse emulsion for nanoencapsulation of hydrophilic assets is the subject of patent application No. P1100 959-6 (PI 1001959-6; OLIVEIRA, MA, TEDESCO, A. C, RÉ, MI; CERIZE, NNP). ; Colloidal Nanocarriers for Hydrophilic Assets and Production Process, 2010). In the method, an aqueous solution of hydrophilic active ingredient and polymer was nanoemulsified into a hydrophobic oil, and the resulting emulsion was subjected to distillation for water removal and nanoparticle formation. The formed nanoparticles do not, however, appear as shell-core structures.

019. Os documentos citados fazem uso de emulsões inversas de água em óleo (a/o), ou emulsões clássicas de óleo em água (o/a). Para as emulsões clássicas, o processo de formação das partículas baseia-se na extração, por destilação, de algum solvente orgânico. Nos trabalhos nos quais se faz o uso de emulsão dupla, trata-se de emulsões de água em óleo em água (a/o/a), nas quais também foi extraída a fase intermediária para a obtenção de partículas, porém a fase intermediária contendo solvente orgânico, com o uso de polímeros hidrofóbicos e água compondo as fases interna e externa. Ainda, nos trabalhos são produzidas partículas na escala micrométrica, à exceção de um deles no qual nanopartículas são produzidas, porém a partir de uma emulsão inversa simples. 020. Nenhum dos trabalhos citados faz uso de uma dupla emulsão inversa contendo três fases distintas, sendo a mais interior composta por um solvente orgânico contendo o ativo solubilizado, a intermediária composta por um polímero hidrofílico em solução aquosa, e a fase externa composta por um óleo silofílico, com redução de tamanho até atingir a escala nanométrica, e extraçâo da fase aquosa intermediária durante o processo para a obtenção de nanocápsulas. 019. The cited documents make use of reverse water-in-oil (w / w) emulsions, or classic oil-in-water (w / w) emulsions. For classical emulsions, the particle formation process is based on the extraction by distillation of some organic solvent. In the works in which the double emulsion is used, these are water-in-water (w / o / a) emulsions, in which the intermediate phase was also extracted to obtain particles, but the intermediate phase containing organic solvent, with the use of hydrophobic polymers and water composing the internal and external phases. Also, in the works particles in the micrometer scale are produced, except for one in which nanoparticles are produced, but from a simple inverse emulsion. 020. None of the works cited makes use of a double inverse emulsion containing three distinct phases, the innermost one consisting of an organic solvent containing the solubilized active, the intermediate composed of a hydrophilic polymer in aqueous solution, and the outer phase composed of a silophilic oil, reduced in size to the nanometer scale, and extraction of the intermediate aqueous phase during the process to obtain nanocapsules.

021. O "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA E PRODUTOS RESULTANTES" compreende um método para a nanoencapsulação de ativo pouco solúvel em água. A encapsulaçâo é obtida através da dissolução do ativo em um solvente imiscível ou pouco miscível com água, e com ponto de ebulição maior que o da água, que é pré-emulsionado em uma solução aquosa contendo polímeros hidrofílicos. Esta pré-emulsão é novamente emulsionada em um óleo lipofílico, dando origem a uma dupla emulsão inversa. A dupla emulsão inversa passa ainda por homogeneização de alta pressão, e a nanoemulsão resultante é submetida à destilação para extraçâo da água da fase intermediária.  021. The "Nanoencapsulation Method of Double Reverse Emulsion Assets and Resulting Products" comprises a method for the nanoencapsulation of poorly water soluble assets. Encapsulation is achieved by dissolving the active in a water-immiscible or low-miscible solvent with a boiling point greater than water, which is pre-emulsified in an aqueous solution containing hydrophilic polymers. This preemulsion is again emulsified in a lipophilic oil, giving rise to a double inverse emulsion. The double inverse emulsion is further subjected to high pressure homogenization, and the resulting nanoemulsion is subjected to distillation to extract water from the intermediate phase.

022. O método possibilita a obtenção de uma suspensão de nanoparticulas do tipo casca-núcleo, contendo ativo pouco solúvel em água dissolvido em um solvente no núcleo e casca composta de polímero hidrofílico sólido. A fase externa da suspensão é um óleo hidrofóbico do tipo silofílico.  022. The method makes it possible to obtain a suspension of core-shell nanoparticles containing poorly water-soluble active material dissolved in a core solvent and shell composed of solid hydrophilic polymer. The external phase of the suspension is a hydrophobic silophilic type oil.

DESCRIÇÃO DAS FIGURAS  DESCRIPTION OF THE FIGURES

023. Figura 1 -mostra as curvas de distribuição de tamanhos para a amostra com 3,7 % de ativo, sendo que as curvas indicam medidas em triplicata da mesma amostra.  023. Figure 1 -shows the size distribution curves for the 3.7% active sample, with the curves indicating triplicate measurements of the same sample.

024. Figura 2 - fotomicrografia dos nanoencapsulados com 3,7 % de ativo, na ordem nanométrica.  024. Figure 2 - photomicrograph of the nanocapsulated with 3.7% active, in nanometric order.

025. Figura 3 - mostra as curvas de distribuição de tamanhos para a amostra com 2,2 % de ativo, sendo que as curvas indicam medidas em triplicata da mesma amostra.  025. Figure 3 - shows the size distribution curves for the 2.2% active sample, with the curves indicating triplicate measurements of the same sample.

026. Figura 4 - fotomicrografia dos nanoencapsulados com 2,2 % de ativo, na ordem nanométrica 027. Figura 5 - mostra as curvas de distribuição de tamanhos para a amostra com 8,0 % de ativo, sendo que as curvas indicam medidas em triplicata da mesma amostra. 026. Figure 4 - Photomicrograph of nanocapsulated with 2.2% active nanometer order 027. Figure 5 - shows the size distribution curves for the 8.0% active sample, with the curves indicating triplicate measurements of the same sample.

028. Figura 6 - fotomicrografia dos nanoencapsulados com 8,0 % de ativo, na ordem nanométrica.  028. Figure 6 - photomicrograph of nanoencapsulated with 8.0% active nanometer order.

029. Figura 7 - mostra as curvas de distribuição de tamanhos para a amostra com 3,4 % de ativo, sendo que as curvas indicam medidas em triplicata da mesma amostra.  029. Figure 7 - shows the size distribution curves for the 3.4% active sample, with the curves indicating triplicate measurements of the same sample.

030. Figura 8 - fotomicrografia dos nanoencapsulados com 3,4 % de ativo, na ordem nanométrica.  030. Figure 8 - photomicrograph of the nanocapsulated with 3.4% active nanometer order.

031. Figura 9 - mostra as curvas de distribuição de tamanhos para a amostra com 3,2 % de ativo, sendo que as curvas indicam medidas em triplicata da mesma amostra.  031. Figure 9 - shows the size distribution curves for the 3.2% active sample, with the curves indicating triplicate measurements of the same sample.

032. Figura 10 - fotomicrografia dos nanoencapsulados com 3,2% de ativo, na ordem nanométrica.  032. Figure 10 - photomicrograph of the nanocapsulated with 3.2% active, in nanometric order.

DETALHAMENTO DA INVENÇÃO  DETAIL OF THE INVENTION

033. Diversos produtos baseados em suspensões aquosas de ativos pouco solúveis em água sofrem com problemas decorrentes de lixiviação quando da aplicação em ambientes externos e ação de chuva, podendo ainda ser suscetíveis à degradação provocada por fatores ambientais.  033. Several products based on aqueous suspensions of poorly water-soluble assets suffer from problems with leaching when applied outdoors and rain and may also be susceptible to degradation caused by environmental factors.

034. O emprego de substâncias encapsuladas vem se tornando uma alternativa cada vez mais viável para obtenção de produtos com maior resistência à lixiviação e a fenómenos naturais, inclusive no que tange a produtos baseados em princípios ativos pouco solúveis em água. Além disso, a capacidade de se obter propriedades de liberação controlada é de interesse por ser conferir alto valor agregado aos produtos.  034. The use of encapsulated substances has become an increasingly viable alternative to obtain products with greater resistance to leaching and natural phenomena, including products based on poorly soluble active ingredients. In addition, the ability to achieve controlled release properties is of interest as it provides high added value to products.

035. O advento da nanotecnologia na área de encapsulação de substâncias ativas possibilita engendrar estruturas em escala nanométrica que permitem maior controle nos mecanismo de liberação e ação dos ativos que são apresentados na forma de um nanoencapsulado.  035. The advent of nanotechnology in the area of encapsulation of active substances makes it possible to engineer nanoscale structures that allow greater control in the mechanisms of release and action of assets that are presented as a nanoencapsulated.

036. O "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLAEMULSÃO INVERSA E PRODUTOS RESULTANTES" é uma forma de obtenção de nanoencapsulados mediante a dupla emulsifica ão inversa seguida de extraçâo dà fase intermediária por destilação. 036. The "Method of NANOENCAPSULATION OF INVERSE DUPLAEMULSION ASSETS AND RESULTING PRODUCTS" is a form of obtaining nanoencapsulated by double inverse emulsification followed by extraction of the intermediate phase by distillation.

037. Este método é compreendido pela execução de cinco etapas de processamento consecutivas que permite a geração dos nanoencapsulados. Estas etapas são: a) solubilização dos ativos a ser nanoencapsulados; b) pré- emulsificação de uma fase contendo os ativos solubifizados em um solvente imiscível ou pouco miscível em água em uma fase aquosa saturada do solvente e contendo material encapsulante; c) emulsificação desta pré-emulsão resultante em um óleo silofílico contendo emutsificantes; d) nanoemulsificação desta dupla emulsão; e e) destilação para extraçâo de água da fase intermediária e formação das nanocápsulas.  037. This method is comprised of the execution of five consecutive processing steps that allows the generation of nanoencapsulates. These steps are: a) solubilization of the assets to be nanocapsulated; b) pre-emulsifying a phase containing the assets solubilized in a water immiscible or poorly miscible solvent in a saturated aqueous phase of the solvent and containing encapsulating material; c) emulsifying this resulting preemulsion into a silophilic oil containing emutants; d) nanoemulsification of this double emulsion; and e) distillation for water extraction from the intermediate phase and formation of nanocapsules.

038. A preparação da etapa a) ou fase orgânica, é realizada por meio de agitação mecânica ou magnética do solvente e dos ativos a ser nanoencapsulados. A agitação é realizada até a completa solubilização dos ativos, em temperatura variando de 5 a 90°C, preferencialmente 23°C, sob agitação de 5 a 3.000 rpm, preferencialmente 400 rpm, em pressão ambiente. O solvente utilizado deve ser imiscível ou pouco miscível em água e possuir ponto de ebulição maior que o da água, preferencialmente 205 °C. Os ativos devem ter caráter hidrofóbico ou parcialmente hidrofílico ou combinações entre eles.  038. The preparation of step a) or organic phase is carried out by mechanical or magnetic stirring of the solvent and the actives to be nanocapsulated. Stirring is performed until complete solubilization of the assets at a temperature ranging from 5 to 90 ° C, preferably 23 ° C, with stirring from 5 to 3,000 rpm, preferably 400 rpm, at ambient pressure. The solvent used should be immiscible or poorly water miscible and boiling higher than water, preferably 205 ° C. The assets must be hydrophobic or partially hydrophilic or combinations of them.

039. A presente invenção pode disponibilizar formulações contendo ingrediente(s) ativo(s) de natureza química ou biológica que atue(m) na área desejada, podendo ser pelo menos um fungicida, inseticida, sinergista de inseticida, larvicida, repelente de artrópodes, disruptor de acasalamento, feromónio, acaricida, algicida, virucida, nematicida, moluscicida, herbicida, protetor contra herbicida, regulador de crescimento, promotor de crescimento, estimulante de frutificação, preservador de flores e/ou frutos, ingrediente de prevenção à queda prematura de flores e/ou frutos, repelente de pássaros, avicida, rodenticida, repelente de mamíferos, inibidor de herbivorismo, esterilizante químico, mas não se limitando a estes, nem a mistura destes, preferencialmente ingredientes ativos pertencentes a esse grupo com uma solubilidade em água inferior a 100 g/l. 040. O material encapsulante é polímero natural ou sintético como, por exemplo, polímeros polissacarídeos, proteína de origem animal ou vegetal, quitosana, gomas (goma arábica, goma xantana, goma guar, goma carragena, goma de cajueiro, goma tara, goma tragacante, goma Karaya, goma gati), derivados de celulose (carboximetil celulose, carboxietil celulose, etc), polivinilpirrolidona, poliacrilatos, poliacrilamidas, polivinilcaprolactamas, bem como suas misturas, preferencialmente os polissacarídeos como o amido. Os polímeros são utilizados dissolvidos em água em concentração de 4% a 35% em massa, preferencialmente 22%, sendo a água utilizada saturada do solvente que compõe a fase orgânica anteriormente à solubilização dos polímeros e os solventes serem ésteres de cadeia longa, os aromáticos, e os hidrocarbonetos. A esta solução também é adicionado um sal orgânico ou inorgânico, adicionado em concentrações que variam entre 0,1 a 10% em massa, preferencialmente 1% m/m, que atua como eletrólito para co-estabilização durante a segunda etapa de emulsificação, sendo tais sais hidrossolúveis, preferencialmente cloretos mono ou bivalentes. 039. The present invention may provide formulations containing chemical or biological active ingredient (s) acting in the desired area and may be at least one fungicide, insecticide, insecticide synergist, larvicide, arthropod repellent, mating disruptor, pheromone, acaricide, algaecide, virucide, nematicide, molluscicide, herbicide, herbicide protector, growth regulator, growth promoter, fruiting stimulant, flower and / or fruit preservative, early flower fall prevention ingredient and / or fruit, bird repellent, avicide, rodenticide, mammal repellent, herbivorism inhibitor, chemical sterilizer, but not limited to or mixture thereof, preferably active ingredients belonging to that group with a water solubility of less than 100 g / l. 040. The encapsulating material is natural or synthetic polymer such as polysaccharide polymers, animal or vegetable protein, chitosan, gums (gum arabic, xanthan gum, guar gum, carrageenan gum, cashew gum, tara gum, tragacanth gum). , Karaya gum, gati gum), cellulose derivatives (carboxymethyl cellulose, carboxyethyl cellulose, etc.), polyvinylpyrrolidone, polyacrylates, polyacrylamides, polyvinylcaprolactams, and mixtures thereof, preferably polysaccharides such as starch. The polymers are used dissolved in water in a concentration of 4% to 35% by weight, preferably 22%, the water used being saturated with the solvent that makes up the organic phase prior to solubilization of the polymers and the solvents being long chain esters, the aromatics , and hydrocarbons. To this solution is also added an organic or inorganic salt, added at concentrations ranging from 0.1 to 10% by weight, preferably 1% w / w, which acts as an electrolyte for co-stabilization during the second emulsification step. such water soluble salts, preferably mono or bivalent chlorides.

041. A segunda etapa (etapa b) que compõe o método é a pré- emulsificação das duas soluções (solução de ativos em solvente e solução de polímero em água) descritas anteriormente. A pré-emulsificação é realizada por meio de agitação mecânica ou magnética da fase orgânica na fase aquosa em velocidade mínima de100 rpm, preferencialmente 1.000 rpm, em temperatura variando de 5 a 90 °C, preferencialmente 23°C e pressão ambiente. A relação fase orgânica e fase aquosa pode variar de 1:1 até 1 :50 em massa, haja vista que para ativos farmacêuticos de alto custo pode-se usar o sistema bem diluído, preferencialmente 1 :2 em massa.  041. The second step (step b) that composes the method is the preemulsification of the two solutions (solvent active solution and polymer in water solution) described above. Preemulsification is carried out by mechanical or magnetic stirring of the organic phase in the aqueous phase at a minimum speed of 100 rpm, preferably 1,000 rpm, at a temperature ranging from 5 to 90 ° C, preferably 23 ° C and ambient pressure. The ratio of organic phase to aqueous phase may vary from 1: 1 to 1: 50 by mass, since for high cost pharmaceutical actives the well-diluted system, preferably 1: 2 by mass may be used.

042. A terceira etapa (etapa c) consiste na emulsificação da pré-emulsão gerada na etapa b) em um emulsificante diluído em óleo hidrofóbico do tipo silofílico, sendo utilizados emulsificantes compatíveis com a fase silofílica, por exemplo, emulsificantes siliconados ou silicone modificado com polioxídoetileno. Esta emulsificação é realizada por agitação mecânica da pré-emulsão na fase silofílica, em velocidade variando de 100 a 30.000 rpm (que para ativos farmacêuticos de alto custo pode-se usar o sistema bem diluído), preferencialmente 1.000 rpm; temperatura variando de 5 a 90 °C, preferencialmente 23°C e pressão ambiente, sendo que a relação de pré-emulsão na fase silofílica pode variar entre 2:1 até 1 :20 em massa (para ativos farmacêuticos de alto custo pode-se usar o sistema bem diluído), preferencialmente 1 :1 em massa. 042. The third step (step c) is the emulsification of the preemulsion generated in step b) into a hydrophobic dilute emulsifier of the silophilic type, using emulsifiers compatible with the silophilic phase, for example, silicone emulsifiers or silicon-modified silicone. polyoxydeethylene. This emulsification is performed by mechanical agitation of the pre-emulsion in the silophilic phase at speeds ranging from 100 to 30,000 rpm (which for high cost pharmaceutical actives can be used well diluted system), preferably 1,000 rpm; temperature ranging from 5 to 90 ° C, preferably 23 ° C and ambient pressure, and the pre-emulsion ratio in the silophilic phase may range from 2: 1 to 1: 20 by mass (for high cost pharmaceutical actives use the well-diluted system), preferably 1: 1 by mass.

043. A quarta etapa (etapa d) é a nanoemulsificação da dupla emulsão resultante da etapa c). Esta nanoemulsificação é realizada com o auxílio de homogeneização de alta pressão, utilizando-se um número de ciclos entre o mínimo de 1 até o necessário para se atingir a granulometria desejada, geralmente inferior a 20 ciclos, preferencialmente 5 ciclos. A pressão utilizada no processo deve ser no mínimo 50 bar e no máximo 2.000 bar, sendo utilizada preferencialmente a pressão de 1000 bar. A temperatura empregada no processo varia de 10 a 100 °C, preferencialmente ambiente.  043. The fourth step (step d) is the nanoemulsification of the double emulsion resulting from step c). This nanoemulsification is carried out with the aid of high pressure homogenization, using a number of cycles from a minimum of 1 to that required to achieve the desired particle size, generally less than 20 cycles, preferably 5 cycles. The pressure used in the process should be a minimum of 50 bar and a maximum of 2,000 bar, preferably 1000 bar. The temperature employed in the process ranges from 10 to 100 ° C, preferably ambient.

044. A quinta etapa (etapa e) consiste na extração da água da fase intermediária (fase externa da emulsão gerada na etapa b) por meio de destilação à pressão reduzida, temperatura elevada e agitação moderada. A destilação é conduzida a uma pressão inferior a 760 mmHg, preferencialmente 140 mmHg, e temperatura entre 23 °C e 90 °C, preferencialmente 50 °C, pelo tempo necessário até a remoção da água do sistema, que pode levar de 10 minutos até20 horas, em geral 3 horas. ·  044. The fifth step (step e) is the extraction of water from the intermediate phase (external phase of the emulsion generated in step b) by distillation under reduced pressure, elevated temperature and moderate agitation. Distillation is conducted at a pressure of less than 760 mmHg, preferably 140 mmHg, and a temperature between 23 ° C and 90 ° C, preferably 50 ° C, for as long as necessary to remove water from the system, which may take from 10 minutes to 20 minutes. hours, usually 3 hours. ·

045. Para disponibilizar a "NANOENCAPSULAÇÂO DE ATIVOS EM DUPLA EMULSÃO INVERSA E PRODUTOS RESULTANTES" para proteção vegetal e ou animal, consiste também a preparação de uma formulação contendo ingrediente(s) ativo(s) preferencialmente formulações de agroquímicos, mais preferencialmente as formulações para diluição/dispersão em água, não se limitando á estas, que contenham um ou mais ingredientes ativos, para diluição/dispersão em água, e/ou diluição/dispersão em solventes orgânicos, e/ou aplicação direta e/ou aplicação para tratamento de sementes,  045. To make available the "NANOENCAPSULATION OF DOUBLE INVERSE EMULSION ASSETS AND RESULTANT PRODUCTS" for plant and / or animal protection, also consists of the preparation of a formulation containing active ingredient (s) preferably formulations of agrochemicals, more preferably formulations for dilution / dispersion in water, but not limited to, containing one or more active ingredients for dilution / dispersion in water, and / or dilution / dispersion in organic solvents, and / or direct application and / or seed treatment application ,

046. Para a obtenção de um acurado balanceamento dos componentes inertes da fórmula, garantindo excepcionais propriedades físico-químicas, por exemplo (mas não exclusivamente) excelente molhabilidade e dispersibilidade (abertura) em água, elevada suspensibilidade, alta estabilidade na dispersão em meios contendo altas concentrações de ions polivalentes (água dura), são utilizados tensoativos (que atuam como agentes dispersantes e umectantes), modificadores reológicos, agentes antiespumantes, agentes desagregantes, agentes diluentes, cargas, reguladores de pH, agentes conservantes, entre outros já comumente utilizados em formulações para proteção vegetal e/ou animal, preferencialmente de agroquímicos, mais preferencialmente as formulações com partículas em suspensão para diluição/dispersão em água, não se limitando a estas fazendo da escolha dos componentes de balanceamento os quais deverão ser escolhidos conforme o tipo de formulação, para atender os requisitos da ABNT NBR 12679 (2o. Ed. 31/03/04) - Agrotóxicos e Afins - Produtos Técnicos e formulações - Terminologia. 046. For accurate balancing of the inert components of the formula, ensuring exceptional physicochemical properties, for example (but not exclusively) excellent wettability and water dispersibility (openness), high suspensibility, high dispersion stability in media containing high concentrations of polyvalent ions (hard water), surfactants (which act as dispersing and wetting agents), rheological modifiers, defoaming agents, disintegrating agents, diluting agents, fillers, pH regulators, preservatives, among others are used. used in plant and / or animal protection formulations, preferably from agrochemicals, more preferably suspended particulate formulations for dilution / dispersion in water, but not limited to balancing components which should be chosen according to type. formulation to meet the requirements of NBR 12679 (2nd Ed 31/03/04..) - Pesticides and Similar Products - Products Technical and formulations - Terminology.

EXEMPLOS  EXAMPLES

047. EXEMPLO 1 - NANOENCAPSULAÇÂO DO ATIVO MODELO ACETAMJPRID em CONCENTRAÇÃO DE 3,7%.  047. EXAMPLE 1 - NANOENCAPSULATION OF ACETAMJPRID ACTIVE MODEL AT 3.7% CONCENTRATION.

048. Em um béquer, 9,0 g de acetamipríd foram dissolvidos em 10,0 gramas de álcool benzílico, à temperatura ambiente. Esta solução foi misturada em 66,3 g de uma solução aquosa contendo 15,0 g de amido Slowfíake G2310® (ComProducts),1 ,5 g de álcool benzílico e 1 ,8 g de cloreto de sódio, com o auxílio de um agitador a 1000 rpm. 048. In a beaker, 9.0 g of acetamiprid was dissolved in 10.0 grams of benzyl alcohol at room temperature. This solution was mixed in 66,3 g of an aqueous solution containing 15,0 g of Slowfíake G2310 ® starch (ComProducts), 1,5 g of benzyl alcohol and 1,8 g of sodium chloride with the aid of a stirrer. at 1000 rpm.

049. O material obtido foi misturado a 100 g de uma fase silofílica composta por óleo de silicone, Xiameter PMX-200 100 OffDow Corning), contendo 10% de emulsificante, SF-1540® (Momentivé), com o auxílio de agitador a 000 rpm. Esta emulsão foi então submetida a 5 ciclos de emulsificação de alta pressão, à pressão de 1000 bar.  049. The obtained material was mixed with 100 g of a silica oil phase composed of silicone oil, Xiameter PMX-200 100 OffDow Corning), containing 10% emulsifier, SF-1540® (Momentivé), with the aid of stirrer at 000 ° C. rpm This emulsion was then subjected to 5 cycles of high pressure emulsification at 1000 bar pressure.

050. A nanoemulsão resultante desta operação foi submetida à destilação em um reator de vidro encamisado, dotado de agitação mecânica, com circulação de água a 50 °C, à pressão de 110 mmHg, por 7 horas.  050. The nanoemulsion resulting from this operation was subjected to distillation in a jacketed glass reactor, mechanically agitated, with water circulation at 50 ° C at 110 mmHg pressure for 7 hours.

051. Após a destilação, o nanoencapsulado resultante foi submetido à análise granulométrica por técnica de espalhamento dinâmico, morfológica por microscopia eletrônica de varredura e teor total de ativos por cromatografia líquida de alto desempenho. 052. A Figura 1 mostra a curva de distribuição de tamanhos para as nanocápsulas obtidas, com média em torno de 400 nm. A Figura 2 mostra a morfologia das partículas obtidas. 051. After distillation, the resulting nanoencapsulated was subjected to particle size analysis by dynamic scattering, morphological scanning electron microscopy and total active content by high performance liquid chromatography. 052. Figure 1 shows the size distribution curve for the obtained nanocapsules, averaging around 400 nm. Figure 2 shows the morphology of the obtained particles.

053. EXEMPLO 2 - Nanoencapsulação DO ATIVO MODELO ACETAMIPRID EM CONCENTRAÇÃO DE 2,2%.  053. EXAMPLE 2 - Nanocapsulation of the ACETAMIPRID MODEL ASSET IN CONCENTRATION of 2.2%.

054. Em um béquer, 3,0 g de acetamiprid foram dissolvidos em 12,0 gramas de álcool benzílico, à temperatura ambiente. Esta solução foi misturada em 66,8 g de uma solução aquosa contendo 15,0 g de amido, Slowfíake G2310® (CornProducts), 1 ,5 g de álcool benzílico e 1 ,8 g de cloreto de sódio, com o auxílio de um agitador a 1000 rpm. 054. In a beaker, 3.0 g of acetamiprid was dissolved in 12.0 grams of benzyl alcohol at room temperature. This solution was mixed in 66,8 g of an aqueous solution containing 15,0 g of starch, Slowfíake G2310 ® (CornProducts), 1,5 g of benzyl alcohol and 1,8 g of sodium chloride with the aid of a stirrer at 1000 rpm.

055. O material obtido foi misturado a 100 g de uma fase silofílica composta por óleo de silicone, Xiameter PMX-200 100 CS® (Dow CorningJ.contendo 10% de emulsificante específico, SF-1540® (Momentive), com o auxílio de agitador a 1000 rpm. Esta emulsão foi então submetida a 5ciclos de emulsificação de alta pressão, à pressão de 1000 bar.  055. The obtained material was mixed to 100 g of a siliaphilic phase composed of silicone oil, Xiameter PMX-200 100 CS® (Dow Corning J. containing 10% specific emulsifier SF-1540® (Momentive), with the aid of stirrer at 1000 rpm This emulsion was then subjected to 5 cycles of high pressure emulsification at 1000 bar pressure.

056. A nanoemulsão resultante desta operação foi submetida à destilação em um reator de vidro encamisado, dotado de agitação mecânica, com circulação de água a 70 °C, â pressão de 170 mmHg, por 5 horas.  056. The nanoemulsion resulting from this operation was subjected to distillation in a jacketed glass reactor, mechanically agitated, with water circulation at 70 ° C, at a pressure of 170 mmHg, for 5 hours.

057. Após a destilação, o nanoencapsulado resultante foi submetido â análise granulométrica por técnica de espalhamento dinâmico, morfológica por microscopia eletrônica de varredura e teor total de ativos por cromatografia líquida de alto desempenho.  057. After distillation, the resulting nanoencapsulated was subjected to particle size analysis by dynamic scattering technique, morphological scanning electron microscopy and total active content by high performance liquid chromatography.

058. A Figura 3 mostra a curva de distribuição de tamanhos para as nanocápsulas obtidas, com média em torno de 350nm. A Figura 4 mostra a morfologia das partículas obtidas.  058. Figure 3 shows the size distribution curve for the nanocapsules obtained, averaging around 350nm. Figure 4 shows the morphology of the obtained particles.

059. EXEMPLO 3 - Nanoencapsulação do ativo modelo acetamiprid em concentração de 8,0%.  059. EXAMPLE 3 - Nanocapsulation of the active model acetamiprid at a concentration of 8.0%.

060. Em um béquer, 12,0 g de acetamiprid foram dissolvidos em 18,3 gramas de álcool benzílico, à temperatura ambiente. Esta solução foi misturada em 66,7 g de uma solução aquosa contendo 14,9 g de amido, Slowfíake G2310® (Corn Products), 1 ,6 g de álcool benzílico e 1 ,8 g de cloreto de sódio, com o auxílio de um agitador a 1000 rpm. 061. O material obtido foi misturado a 100 g de uma fase silofílica composta por óleo de silicone, Xiameter PMX-200 100 CS® (Dow Corning), contendo 10% de emulsificante específico SF- 540® (Momentive), com o auxílio de agitador a 1000 rpm. Esta emulsão foi então submetida a cinco ciclos de emulsificação de alta pressão, à pressão de 1000 bar. 060. In a beaker, 12.0 g of acetamiprid was dissolved in 18.3 grams of benzyl alcohol at room temperature. This solution was mixed in 66.7 g of an aqueous solution containing 14.9 g of starch, Slowfíake G2310® (Corn Products), 1.6 g of benzyl alcohol and 1.8 g of sodium chloride with the aid of a stirrer at 1000 rpm. 061. The material obtained was mixed with 100 g of a siliaphilic phase composed of silicone oil, Xiameter PMX-200 100 CS® (Dow Corning), containing 10% SF-540® specific emulsifier (Momentive), with the aid of stirrer at 1000 rpm. This emulsion was then subjected to five cycles of high pressure emulsification at 1000 bar pressure.

062. A nanoemulsão resultante desta operação foi submetida â destilação em um reator de vidro encamisado, dotado de agitação mecânica, com circulação de água a 35 °C, à pressão de 95mmHg,por 9 horas.  062. The nanoemulsion resulting from this operation was subjected to distillation in a jacketed glass reactor, mechanically agitated, with water circulation at 35 ° C at a pressure of 95mmHg for 9 hours.

063. Após a destilação, o nanoencapsulado resultante foi submetido â análise granulõmétríca por técnica de espalhamento dinâmico, morfológica por microscopia eletrônica de varredura e teor total de ativos por cromatografia líquida de alto desempenho.  063. After distillation, the resulting nanoencapsulated was subjected to particle size analysis by dynamic scattering technique, scanning electron microscopic morphology and total active content by high performance liquid chromatography.

064. A Figura 5 mostra a curva de distribuição de tamanhos para as nanocápsulas obtidas, com média em torno de 300nm. A Figura 6 mostra a morfologia das partículas obtidas.  064. Figure 5 shows the size distribution curve for the obtained nanocapsules, averaging around 300nm. Figure 6 shows the morphology of the obtained particles.

065. EXEMPLO 4- Nanoencapsulação do ativo modelo acetamiprid em concentração de 3,4%.  065. EXAMPLE 4- Nanoencapsulation of the active model acetamiprid at a concentration of 3.4%.

066. Em um béquer, 4,2 g de acetamiprid foram dissolvidos em 6,5 gramas de álcool benzílico, à temperatura ambiente. Esta solução foi misturada em 45,8 g de uma solução aquosa contendo 10,1 g de amido, Slowflake G2310® (CornProducts),1 ,0 g de álcool benzílico e 1 ,4 g de cloreto de sódio, com o auxílio de um agitador a 1000 rpm.  066. In a beaker, 4.2 g of acetamiprid was dissolved in 6.5 grams of benzyl alcohol at room temperature. This solution was mixed in 45,8 g of an aqueous solution containing 10,1 g of starch, Slowflake G2310® (CornProducts), 1,0 g of benzyl alcohol and 1,4 g of sodium chloride with the aid of a stirrer at 1000 rpm.

067. O material obtido foi misturado a 100 g de uma fase silofílica composta por óleo de silicone, Xiameter PMX-200 100 CS® (Dow Corning) .contendo 10% de emulsificante específico, SF-1540® (Momentive),com o auxílio de agitador a 1000 rpm. Esta emulsão foi então submetida a cinco ciclos de emulsificação de alta pressão, à pressão de 000 bar.  067. The material obtained was mixed to 100 g of a silophilic phase composed of silicone oil, Xiameter PMX-200 100 CS® (Dow Corning). Containing 10% specific emulsifier SF-1540® (Momentive), with the aid of stirrer at 1000 rpm. This emulsion was then subjected to five cycles of high pressure emulsification at a pressure of 000 bar.

068. A nanoemulsão resultante desta operação foi submetida à destilação em um reator de vidro encamisado , dotado de agitação mecânica, com circulação de água a 35 °C, à pressão de 235 mmHg, por 9 horas.  068. The nanoemulsion resulting from this operation was subjected to distillation in a jacketed glass reactor, mechanically agitated, with water circulation at 35 ° C, at a pressure of 235 mmHg, for 9 hours.

069. Após a destilação, o nanoencapsulado resultante foi submetido à análise granulõmétríca por técnica de espalhamento dinâmico, morfológica por microscopia eletrônica de varredura e teor total de ativos por cromatografia líquida de alto desempenho. 069. After distillation, the resulting nanoencapsulated was subjected to particle size analysis by dynamic, morphological scanning electron microscopy and total active content by high performance liquid chromatography.

070. A Figura 7 mostra a curva de distribuição de tamanhos para as nanocápsulas obtidas, com média em torno de 250 nm. A Figura 8 mostra a morfologia das partículas obtidas.  070. Figure 7 shows the size distribution curve for the obtained nanocapsules, averaging around 250 nm. Figure 8 shows the morphology of the obtained particles.

071. EXEMPLO 5- Nanoencapsuíação do atívo modelo acetamiprid em concentração de 3,2%.  071. EXAMPLE 5- Nanocapsulation of the active acetamiprid model at a concentration of 3.2%.

072. Em um béquer, 4,0 g de acetamiprid foram dissolvidos em 6,2 gramas de álcool benzílico, à temperatura ambiente. Esta solução foi misturada em 45,8 g de uma solução aquosa contendo 10,1 g de amido, Slowfiake G23 0® (CornProducts), 1 ,0 g de álcool benzílico e 2,0 g de cloreto de sódio, com o auxílio de um agitador a 1000 rpm.  072. In a beaker, 4.0 g of acetamiprid was dissolved in 6.2 grams of benzyl alcohol at room temperature. This solution was mixed into 45,8 g of an aqueous solution containing 10,1 g of starch, Slowfiake G23® (CornProducts), 1,0 g of benzyl alcohol and 2,0 g of sodium chloride with the aid of a stirrer at 1000 rpm.

073. O material obtido foi misturado a 100 g de uma fase silofílica composta por óleo de silicone, Xiameter PMX-200 100 CS® (Dow Corning), contendo 10% de emuisificante específico,SF-1540® (Momentive),com o auxílio de agitador a 1000 rpm. Esta emulsão foi então submetida a cinco ciclos de emulsificação de alta pressão, à pressão de 1000 bar.  073. The material obtained was mixed to 100 g of a silica oil phase composed of silicone oil, Xiameter PMX-200 100 CS® (Dow Corning), containing 10% specific emulsifier SF-1540® (Momentive), with the aid of stirrer at 1000 rpm. This emulsion was then subjected to five cycles of high pressure emulsification at 1000 bar pressure.

074. A nanoemulsão resultante desta operação foi submetida à destilação em um reator de vidro encamisado com capacidade para 500 mL, dotado de agitação mecânica, com circulação de água a 70 °C, à pressão de 235 mmHg, por 5 horas.  074. The nanoemulsion resulting from this operation was subjected to distillation in a 500 ml jacketed glass reactor with mechanical stirring, with water circulation at 70 ° C, at a pressure of 235 mmHg, for 5 hours.

075. Após a destilação, o nanoencapsulado resultante foi submetido à análise granulométrica por técnica de espalhamento dinâmico, morfológica por microscopia eletrônica de varredura e teor total de ativos por cromatografia líquida de alto desempenho.  075. After distillation, the resulting nanoencapsulated was subjected to particle size analysis by dynamic scattering technique, scanning electron microscopy morphology and total active content by high performance liquid chromatography.

076. Figura 9 mostra a curva de distribuição de tamanhos para as nanocápsulas obtidas, com média em torno de 250 nm, e a Figura 10 mostra a morfologia das partículas obtidas.  076. Figure 9 shows the size distribution curve for the obtained nanocapsules, averaging around 250 nm, and Figure 10 shows the morphology of the particles obtained.

Claims

REIVINDICAÇÕES 1. "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA", caracterizado pela obtenção de nanoencapsulados mediante a dupla emulsificação inversa seguida de extração da fase intermediária por destilação, compreendendo a execução de cinco fases de processamento consecutivas, sendo etapa a) solubilizaçâo dos ativos a serem nanoencapsulados; etapa b) pré-emulsificação de uma fase contendo os ativos solubilizados em um solvente imiscívei ou pouco miscível em água em uma fase aquosa saturada do solvente e contendo material encapsulante; etapa c) emulsificação desta pré-emulsão resultante em um óleo silofilico contendo emulsificantes; etapa d) nanoemulsíficação desta dupla emulsão e etapa e) destilação para extração de água da fase intermediária e formação das nanocápsulas. 1. "METHOD OF NANOENCAPSULATION OF ASSETS IN DOUBLE INVERSE EMULSION", characterized by obtaining nanoencapsulated substances through double inverse emulsification followed by extraction of the intermediate phase by distillation, comprising the execution of five consecutive processing phases, stage a) solubilization of the assets to be nanoencapsulated; step b) pre-emulsification of a phase containing the active ingredients solubilized in an immiscible or poorly miscible solvent in water in an aqueous phase saturated with the solvent and containing encapsulating material; step c) emulsifying this resulting pre-emulsion into a silophilic oil containing emulsifiers; step d) nanoemulsification of this double emulsion and step e) distillation to extract water from the intermediate phase and form nanocapsules. 2. "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 1 , caracterizado por etapa a), ou fase orgânica, ser realizada por meio de agitação mecânica ou magnética do solvente e dos ativos a serem nanoencapsulados, sendo a agitação realizada até a completa solubilizaçâo dos ativos, em temperatura variando de 5 a 90 °C, sob agitação de 5 a 3.000 rpm, em pressão ambiente; o solvente utilizado ser imiscívei ou pouco miscível em água e possuir ponto de ebulição maior que o da água; os ativos terem caráter hidrofóbico ou parcialmente hidrofílico ou combinações entre eles e o material encapsulante ser polímero natural ou sintético, bem como suas misturas; 2. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 1, characterized by step a), or organic phase, being carried out by means of mechanical or magnetic agitation of the solvent and the assets to be nanoencapsulated, being agitation carried out until complete solubilization of the active ingredients, at temperatures ranging from 5 to 90 °C, under agitation from 5 to 3,000 rpm, at ambient pressure; the solvent used is immiscible or poorly miscible in water and has a boiling point higher than that of water; the active ingredients have a hydrophobic or partially hydrophilic character or combinations thereof and the encapsulating material is a natural or synthetic polymer, as well as mixtures thereof; 3. "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 2, caracterizado por os polímeros encapsulantes serem utilizados dissolvidos em água em concentração de 4% a 35%, sendo a água utilizada saturada do solvente que compõe a fase orgânica anteriormente à solubilizaçâo dos polímeros, e a esta solução também ser adicionado um sal orgânico ou inorgânico hidrossolúvel, em concentrações que variam entre 0,1 a 10%, que atua como eletrólito para co- estabilização durante a segunda etapa de emulsificação; 3. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 2, characterized in that the encapsulating polymers are used dissolved in water at a concentration of 4% to 35%, with the water used being saturated with the solvent that makes up the organic phase prior to the solubilization of the polymers, and a water-soluble organic or inorganic salt is also added to this solution, in concentrations ranging between 0.1 and 10%, which acts as an electrolyte for co-stabilization during the second emulsification stage; 4. "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 2, caracterizado por o material encapsulante ser polímeros polissacarídeos, proteína de origem animal ou vegetal, quitosana, gomas (goma arábica, goma xantana, goma guar, goma carragena, goma de cajueiro, goma tara, goma tragacante, goma Karaya, goma gati), derivados de celulose (carboximetil celulose, carboxietil celulose, polivinilpirrolidona, poliacrilatos, poliacrilamidas, polivinilcaprolactamas, bem como suas misturas; os ativos serem pelo menos um fungicida, inseticida, sinergista de inseticida, larvicida, repelente de artrópodes, disruptor de acasalamento, feromônio, acaricida, algicída, virucida, nematicida, moluscicida, herbicida, protetor contra herbicida, regulador de crescimento, promotor de crescimento, estimulante de frutificação, preservador de flores e/ou frutos, ingrediente de prevenção à queda prematura de flores e/ou frutos, repelente de pássaros, avicida, rodenticida, repelente de mamíferos, inibidor de herbivorismo, esterilizante químico, ou suas misturas, preferencialmente ingredientes ativos pertencentes a esse grupo com uma solubilidade em água inferior a 100 g/l; os solventes serem ésteres de cadeia longa, os aromáticos, e os hidrocarbonetos; e, os sais atuantes como eletrólitos serem cloreto mono ou bivalente; 4. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 2, characterized in that the encapsulating material is polysaccharide polymers, protein of animal or vegetable origin, chitosan, gums (gum arabic, xanthan gum, guar gum, carrageenan gum, cashew gum, tara gum, gum tragacanth, Karaya gum, gati gum), cellulose derivatives (carboxymethyl cellulose, carboxyethyl cellulose, polyvinylpyrrolidone, polyacrylates, polyacrylamides, polyvinylcaprolactams, as well as mixtures thereof; the active ingredients must be at least one fungicide , insecticide, insecticide synergist, larvicide, arthropod repellent, mating disruptor, pheromone, acaricide, algaecide, virucide, nematicide, molluscicide, herbicide, herbicide protectant, growth regulator, growth promoter, fruiting stimulant, flower preserver and/or fruits, ingredient for preventing premature falling of flowers and/or fruits, bird repellent, avicide, rodenticide, mammal repellent, herbivory inhibitor, chemical sterilant, or mixtures thereof, preferably active ingredients belonging to this group with a solubility in water less than 100 g/l; the solvents are long-chain esters, aromatics, and hydrocarbons; and, the salts acting as electrolytes are mono or divalent chloride; 5. "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 4, caracterizado por o material encapsulante ser o amido; os ativos serem acetamiprid; e o solvente ser álcool benzílico. 5. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 4, characterized in that the encapsulating material is starch; the assets are acetamiprid; and the solvent is benzyl alcohol. 6. "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com as reivindicações 1 a 5, caracterizado por a etapa a) ser realizada em temperatura de 23 °C e agitação de 400 rpm, o solvente utilizado possuir ponto de ebulição de 205 °C, o encapsulante ser amido em concentração de 22% em massa, e o sal atuante como eletrólito ser cloreto de sódio em concentração de 1% em massa; 6. "INVERSE DOUBLE EMULSION NANOENCAPSULATION METHOD", according to claims 1 to 5, characterized in that step a) is carried out at a temperature of 23 °C and stirring at 400 rpm, the solvent used has a boiling point 205 °C, the encapsulant will be starch at a concentration of 22% by mass, and the salt acting as electrolyte will be sodium chloride at a concentration of 1% by mass; 7. "MÉTODO DE NANOENCAPSULAÇÃO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicaçãol , caracterizado por a etapa b) de pré-emulsificação ser realizada por meio de agitação mecânica ou magnética da fase orgânica (etapa a) na fase aquosa em velocidade mínima de 100 rpm, em temperatura variando de 5 a 90 °C, pressão ambiente e a relação fase orgânica e fase aquosa variar de 1 : 1 até 1 : 50 em massa. 7. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim, characterized in that step b) of pre-emulsification be carried out by means of mechanical or magnetic agitation of the organic phase (step a) in the aqueous phase at a minimum speed of 100 rpm, at a temperature ranging from 5 to 90 °C, ambient pressure and the ratio of organic phase and aqueous phase to vary from 1 : 1 to 1 : 50 in bulk. 8-. "MÉTODO DE NANOENCAPSULAÇÂO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 7, caracterizado por a etapa b) de pré-emulsificação ser realizada por meio de agitação mecânica ou magnética da fase orgânica (etapa a) na fase aquosa em velocidade de 1.000 rpm, em temperatura de 23 °C e a relação fase orgânica e fase aquosa de 1 :2 em massa. 8-. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 7, characterized in that step b) of pre-emulsification is carried out by means of mechanical or magnetic agitation of the organic phase (step a) in the aqueous phase at speed 1,000 rpm, at a temperature of 23 °C and the organic phase and aqueous phase ratio of 1:2 by mass. 9. "MÉTODO DE NANOENCAPSULAÇÂO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 1 , caracterizado por a terceira etapa (etapa c) consistir na emulsificação da pré-emulsão gerada na etapa b) em um emulsificante diluído em óleo hidrofóbico do tipo silofílico, sendo utilizados emulsificantes compatíveis com a fase silofílica sendo a emulsificação realizada por agitação mecânica da pré-emulsão na fase silofílica, em velocidade variando de 100 a 30.000 rpm; temperatura variando de 5 a 90 °C, e pressão ambiente, sendo que a relação de pré-emulsão na fase silofílica pode variar entre 2:1 até 1:20 em massa. 9. "METHOD OF NANOENCAPSULATION OF ASSETS IN DOUBLE INVERSE EMULSION", according to claim 1, characterized in that the third step (step c) consists of emulsifying the pre-emulsion generated in step b) in an emulsifier diluted in hydrophobic oil of silophilic type, using emulsifiers compatible with the silophilic phase, with emulsification carried out by mechanical agitation of the pre-emulsion in the silophilic phase, at speeds ranging from 100 to 30,000 rpm; temperature ranging from 5 to 90 °C, and ambient pressure, and the pre-emulsion ratio in the silophilic phase can vary between 2:1 and 1:20 by mass. 10. "MÉTODO DE NANOENCAPSULAÇÂO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 9, caracterizado por sendo os emulsificantes compatíveis com a fase silofílica, os emulsificantes siliconados ou silicone modificado com polioxidoetileno; e a emulsificação ser realizada por agitação mecânica da pré-emulsão na fase silofílica, em velocidade de 1.000 rpm; temperatura de 23 °C e pressão ambiente, sendo a relação de pré- emulsão na fase de 1 :1 em massa. 10. "METHOD OF NANOENCAPSULATION OF ASSETS IN DOUBLE INVERSE EMULSION", according to claim 9, characterized in that the emulsifiers are compatible with the silophilic phase, silicone emulsifiers or silicone modified with polyoxydoethylene; and the emulsification is carried out by mechanical agitation of the pre-emulsion in the silophilic phase, at a speed of 1,000 rpm; temperature of 23 °C and ambient pressure, with the pre-emulsion ratio in the phase being 1:1 by mass. 11. "MÉTODO DE NANOENCAPSULAÇÂO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 1 , caracterizado por a quarta etapa (etapa d) ser a nanoemulsificação da dupla emulsão resultante da etapa c) ser realizada com o auxílio de homogeneização de alta pressão, utilizando-se um número de ciclos necessário para se atingir a granulometria desejada, a pressão utilizada no processo ser de 50 bar a 2.000 bar e a temperatura empregada variar de 10 a 00 °C. 11. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 1, characterized in that the fourth step (step d) is the nanoemulsification of the double emulsion resulting from step c) being carried out with the aid of high homogenization pressure, using a number of cycles necessary to achieve the desired granulometry, the pressure used in the process is from 50 bar to 2,000 bar and the temperature used varies from 10 to 00 °C. 2. "MÉTODO DE NANOENCAPSULAÇÂO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 11 , caracterizado por a pressão ser de 1000 bar e a temperatura empregada ser a ambiente. 2. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 11, characterized in that the pressure is 1000 bar and the temperature used is ambient. 13. "MÉTODO DE NANOENCAPSULAÇÂO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 1 , caracterizado por na quinta etapa (etapa e) a destilação ser conduzida a uma pressão inferior a 760 mmHg e temperatura entre 23 °C e 90 °C até a remoção da água do sistema. 13. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 1, characterized in that in the fifth step (step e) the distillation is conducted at a pressure below 760 mmHg and a temperature between 23 °C and 90 °C C until the water is removed from the system. 14. "MÉTODO DE NANOENCAPSULAÇÂO DE ATIVOS EM DUPLA EMULSÃO INVERSA", de acordo com a reivindicação 13, caracterizado por a destilação ser conduzida à pressão de 140 mmHg e temperatura 50 °C pelo tempo de 10 minutos até 20 horas. 14. "METHOD OF NANOENCAPSULATION OF ASSETS IN INVERSE DOUBLE EMULSION", according to claim 13, characterized in that the distillation is carried out at a pressure of 140 mmHg and a temperature of 50 °C for a period of 10 minutes to 20 hours. 15. "PRODUTO", caracterizado por conter ativos nanoencapsulados em dupla emulsão invertida, para proteção vegetal e animal, em formulações para diluição/dispersão em agua, para diluição/dispersão em solventes orgânicos, para aplicação direta e para aplicação em sementes contendo ingredientes ativos de natureza química ou biológica como fungicida, inseticida, sinergista de inseticida, larvicida, repelente de artrópodes, disruptor de acasalamento, feromônio, acaricida, algicida, virucida, nematicida, moluscicida, herbicida, protetor contra herbicida, regulador de crescimento, promotor de crescimento, estimulante de frutificação, preservador de flores e/ou frutos, ingrediente de prevenção à queda prematura de flores e/ou frutos, repelente de pássaros, avicida, rodenticida, repelente de mamíferos, inibidor de herbivorismo, esterilizante químico, com uma solubilidade em água inferior a 100 g/l; conter dois ou mais solventes orgânicos com o ponto de ebulição acima de 00 °C a 760 mmHg; conter tensoativos, modificadores reológicos, agentes antiespumantes, agentes desagregantes, agentes diluentes, cargas, reguladores de pH, agentes conservantes, entre outros já comumente utilizados em formulações para proteção vegetal e/ou animal; 15. "PRODUCT", characterized by containing nanoencapsulated active ingredients in double inverted emulsion, for plant and animal protection, in formulations for dilution/dispersion in water, for dilution/dispersion in organic solvents, for direct application and for application to seeds containing active ingredients of a chemical or biological nature such as fungicide, insecticide, insecticide synergist, larvicide, arthropod repellent, mating disruptor, pheromone, acaricide, algaecide, virucide, nematicide, molluscicide, herbicide, herbicide protector, growth regulator, growth promoter, fruiting stimulant, flower and/or fruit preserver, ingredient to prevent premature falling of flowers and/or fruits, bird repellent, avicidal, rodenticide, mammal repellent, herbivory inhibitor, chemical sterilant, with lower water solubility at 100 g/l; contain two or more organic solvents with a boiling point above 00 °C at 760 mmHg; contain surfactants, rheological modifiers, antifoaming agents, disintegrating agents, diluting agents, fillers, pH regulators, preservative agents, among others already commonly used in formulations for plant and/or animal protection; 16, "PRODUTO" de acordo com a reivindicação 15, caracterizado por conter um, dois ou mais ingredientes ativos na formulação. 16, "PRODUCT" according to claim 15, characterized in that it contains one, two or more active ingredients in the formulation. 17. "PRODUTO" de acordo com a reivindicação 16, caracterizado por utilização, em formulações com partículas em suspensão para diluição/dispersão em água de agroquímicos, com escolha dos componentes de balanceamento escolhidos conforme o tipo de formulação visando atender aos requisitos da ABNT NBR 12679 - Agrotóxicos e Afins - Produtos Técnicos e formulações - Terminologia. 17. "PRODUCT" according to claim 16, characterized by use in formulations with suspended particles for dilution/dispersion of agrochemicals in water, with choice of balancing components chosen according to the type of formulation in order to meet the requirements of ABNT NBR 12679 - Pesticides and the like - Technical products and formulations - Terminology.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117982346A (en) * 2024-03-08 2024-05-07 深圳市羽素生物科技有限公司 A high-stability colloidal sulfur anti-acne essence and preparation method thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6017559A (en) * 1994-07-15 2000-01-25 Dow Agrosciences Llc Preparation of aqueous emulsions
US20100015236A1 (en) * 2006-09-14 2010-01-21 Shlomo Magdassi Pesticide nanoparticles obtained from microemulsions and nanoemulsions
BRPI1001959A2 (en) * 2010-06-15 2012-03-06 Instituto De Pesquisas Tecnológicas Do Est. S. Paulo S/a - Ipt COLLOIDAL NANOCARCHERS FOR HYDROPHYLIC ASSETS AND PRODUCTION PROCESS
WO2013050594A1 (en) * 2011-10-06 2013-04-11 Agrosavfe N.V. Manufacturing of specifically targeting microcapsules

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6017559A (en) * 1994-07-15 2000-01-25 Dow Agrosciences Llc Preparation of aqueous emulsions
US20100015236A1 (en) * 2006-09-14 2010-01-21 Shlomo Magdassi Pesticide nanoparticles obtained from microemulsions and nanoemulsions
BRPI1001959A2 (en) * 2010-06-15 2012-03-06 Instituto De Pesquisas Tecnológicas Do Est. S. Paulo S/a - Ipt COLLOIDAL NANOCARCHERS FOR HYDROPHYLIC ASSETS AND PRODUCTION PROCESS
WO2013050594A1 (en) * 2011-10-06 2013-04-11 Agrosavfe N.V. Manufacturing of specifically targeting microcapsules

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
R OUSSEAU, D. ET AL., J. COLLOID INTERFACE SCI., vol. 386, 2012, pages 398 - 404 *
TAKEI, T. ET AL.: "PREPARATION OF ACETAMIPRID-LOADED POLYMERIC MICROCAPSULES: INFLUENCE OF PREPARATION PARAMETER IN EMULSION SYSTEM ON MICROCAPSULE CHARACTERISTICS;", POLYMER BULLETIN, vol. 61, 2008, pages 119 - 127, XP019625841 *
TAKEI, T. ET AL.: "PREPARATION OF POLYLACTIDE-BASED MICROSPHERES ENCLOSING ACETAMIPRID AND EVALUATION OF EFFICACY AGAINST COTTON APHID BY SOIL APPLICATION", J. APPL. POLYM. SCI., vol. 109, 2008, pages 763 - 766 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN117982346A (en) * 2024-03-08 2024-05-07 深圳市羽素生物科技有限公司 A high-stability colloidal sulfur anti-acne essence and preparation method thereof

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