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WO2010003762A1 - Particules contenant une substance active - Google Patents

Particules contenant une substance active Download PDF

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Publication number
WO2010003762A1
WO2010003762A1 PCT/EP2009/057369 EP2009057369W WO2010003762A1 WO 2010003762 A1 WO2010003762 A1 WO 2010003762A1 EP 2009057369 W EP2009057369 W EP 2009057369W WO 2010003762 A1 WO2010003762 A1 WO 2010003762A1
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Prior art keywords
shell
water
particles
core
soluble
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Ceased
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PCT/EP2009/057369
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German (de)
English (en)
Inventor
Jing Dreher
Ingrid Martin
Sebastian Koltzenburg
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BASF SE
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BASF SE
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Publication of WO2010003762A1 publication Critical patent/WO2010003762A1/fr
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    • 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
    • B01J13/20—After-treatment of capsule walls, e.g. hardening
    • B01J13/22—Coating
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/179—Colouring agents, e.g. pigmenting or dyeing agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K40/00—Shaping or working-up of animal feeding-stuffs
    • A23K40/30—Shaping or working-up of animal feeding-stuffs by encapsulating; by coating
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23P—SHAPING OR WORKING OF FOODSTUFFS, NOT FULLY COVERED BY A SINGLE OTHER SUBCLASS
    • A23P10/00—Shaping or working of foodstuffs characterised by the products
    • A23P10/30—Encapsulation of particles, e.g. foodstuff additives
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B61/00—Dyes of natural origin prepared from natural sources, e.g. vegetable sources
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0097—Dye preparations of special physical nature; Tablets, films, extrusion, microcapsules, sheets, pads, bags with dyes

Definitions

  • the present invention relates to particles having a core-shell-shell structure in which the core contained within each particle comprises at least one sparingly water-soluble or water-insoluble organic agent, a process for producing these particles having the core-shell-shell structure, the use the particle with the core-shell-shell structure and preparations containing the particles with the core-shell-shell structure.
  • WO 2007/015243 describes, for example, the coating of solid, water-insoluble, particulate active substances with metal oxides, the active substance particles being first treated in water with a cationic additive such as cetyltrimethylammonium chloride to produce a positive zeta potential on the particle surface. Subsequently, a metal oxide layer is deposited on the surface of the pretreated particles and allowed to age. The operations of surface treatment with a cationic additive, deposition of a metal oxide layer on the particle surface and aging of the metal oxide are optionally repeated.
  • a cationic additive such as cetyltrimethylammonium chloride
  • J. Mater. Chem., 2006, 16, 3120-3125 describes the production of gelatin nanoparticles and microparticles coated with a silica gel layer.
  • gelatin particles are formed at 5 ° C in an oil phase and isolated.
  • the isolated gelatin particles are redispersed in water at 5 ° C and then added to a buffered at pH 7.2 solution of sodium silicate at room temperature, wherein the gelatin particles are coated by a silica gel layer.
  • the particles produced contain no active ingredient.
  • EP-B 065 193 describes the preparation of finely divided, pulverulent carotenoid preparations in which a carotenoid is dissolved in a volatile, water-miscible organic solvent at elevated temperatures, optionally under elevated pressure, by mixing with an aqueous solution of a carotenoid Protective colloid precipitates and then spray-dried.
  • An analogous process for the preparation of finely divided, pulverulent carotenoid preparations is described in EP-A-0 937 412 using water-immiscible solvents.
  • WO 91/06292 a grinding process is described in which a solid, water-insoluble active ingredient is comminuted in the presence of a protective colloid in an aqueous medium.
  • each particle located in the interior of each particle comprises at least one sparingly water-soluble or water-insoluble organic active substance
  • each core comprises at least one protective colloid, which is a biodegradable polymer
  • the outer shell (shell 2) enclosing the protective colloid-containing shell (shell 1) contains at least one metal or semimetal oxide
  • the particles according to the invention having a core-shell-shell structure each contain a core in the interior which comprises at least one organic substance which is sparingly soluble in water or insoluble in water.
  • the core in the interior of a particle according to the invention preferably consists of more than 50% by weight, more preferably more than 80% by weight, in particular more than 90% by weight, of at least one sparingly water-soluble or water-insoluble organic active substance, based on the mass of the core.
  • the percentage refers to a statistical average determined over a large number of particles.
  • the cores in the interior of the particles according to the invention usually have an average particle size of less than 10,000 nm, preferably an average particle size of less than 1,000 nm, particularly preferably a partial particle size.
  • the particle size for the cores refers to a statistical average determined over a large number of particles.
  • the average particle size of the cores and the thickness of the shells were determined by TEM (Transmission Electron Microscopy).
  • the average particle size can be determined by the methods of light scattering (static and dynamic light scattering).
  • the shape of the cores in the particles according to the invention is arbitrary and may be, for example, irregular or spherical, preferably spherical.
  • suitable organic compounds are those which are used for the food and animal nutrition sector, for pharmaceutical and cosmetic applications or in the field of crop protection.
  • the organic agents are chemical compounds that usually contain both carbon and hydrogen.
  • a sparingly water-soluble organic active substance is usually a chemical compound whose solubility in water at 20 ° C. is less than 10 g / l, preferably less than 1 g / l, particularly preferably less than 0.1 g / l.
  • Active ingredients used in the food and animal nutrition sector include lipophilic vitamins such as tocopherol, vitamin A and its derivatives, vitamin D and its derivatives, vitamin K and its derivatives, vitamin F and its derivatives, or saturated and unsaturated fatty acids Derivatives and compounds thereof, natural and synthetic flavorings, flavors and fragrances and lipophilic dyes, such as retinoids, flavonoids or carotenoids.
  • lipophilic vitamins such as tocopherol, vitamin A and its derivatives, vitamin D and its derivatives, vitamin K and its derivatives, vitamin F and its derivatives, or saturated and unsaturated fatty acids Derivatives and compounds thereof, natural and synthetic flavorings, flavors and fragrances and lipophilic dyes, such as retinoids, flavonoids or carotenoids.
  • Active substances used in the pharmaceutical sector include anesthetics and narcotics, anticholinergics, antidepressants, psychostimulants and neuroleptics, antiepileptics, antimycotics, antiphlogistics, bronchodilators, cardiovascular drugs, cytostatics, hyperemics, lipid-lowering drugs, spasmolytics, testosterone derivatives, tranquilizers or antivirals.
  • Crop protection agents are lipophilic agrochemicals such as insecticides, fungicides, pesticides, nematicides, rodenticides, molluscicides, growth regulators and herbicides.
  • pesticide denotes at least one active substance selected from the group of fungicides, insecticides, nematicides, herbicides, rodenticides, safeners and / or growth regulators.
  • Preferred pesticides are fungicides, insecticides, rodenticides and herbicides.
  • mixtures of pesticides of two or more of the above classes may be used.
  • One skilled in the art is familiar with such pesticides as described, for example, in Pesticide Manual, 14th Ed. (2006), The British Crop Protection Council, London.
  • a fat-soluble vitamin or a carotenoid in particular a carotenoid, as a sparingly water-soluble or water-insoluble organic active substance.
  • an organic UV filter is used as poorly water-soluble or water-insoluble organic active substance in the cores of the particles according to the invention, such as benzophenone-3, butyl methoxydibenzoylmethane, ethylhexyl triazone, drometrizole trisiloxanes, diethylhexyl butamido triazone, 4-methylbenzylidene camphor, 3-benzylidenes Camphor, methylene bis-benzotriazolyl tetramethylbutylphenol, bis-ethylhexyloxyphenol methoxyphenyl triazine or diethylamino hydroxybenzoyl hexyl benzoates, in particular ethylhexyl triazone, diethylamino hydroxybenzoyl hexyl benzoate, methylene bis-benzotriazolyl tetramethylbutylphenol or bis-ethylhexyloxyphenol me
  • the sparingly water-soluble or water-insoluble organic active substance may be a liquid or a solid at 20 ° C., whereby the solid itself may also be present in a suitable lipophilic solvent, such as an oil, in dissolved form or as a suspension.
  • the sparingly water-soluble or water-insoluble organic active substance used in the particles according to the invention is preferably a solid at 20 ° C.
  • the sparingly water-soluble or water-insoluble organic active ingredient is particularly preferably a carotenoid, for example ⁇ -carotene, astaxanthin, canthaxanthin, citranaxanthin, lycopene or lutein.
  • a carotenoid for example ⁇ -carotene, astaxanthin, canthaxanthin, citranaxanthin, lycopene or lutein.
  • the shell directly surrounding each core (shell 1) contains at least one protective colloid, which is a biodegradable polymer.
  • Suitable protective colloids include, for example, both electrically charged polymers (polyelectrolytes) and neutral polymers.
  • Typical examples include gelatin such as beef, pork or fish gelatin, starch, modified starch such as octenyl succinate starch, dextrin, vegetable proteins such as soy proteins, which may optionally be hydrolyzed, xanthan, casein, caseinates such as sodium caseinate, lignin sulfonate or mixtures from that.
  • homopolymers and copolymers based on neutral, cationic or anionic monomers such as, for example, ethylene oxide, propylene oxide, acrylic acid, maleic anhydride, N-vinylpyrrolidone, vinyl acetate, ⁇ - and ⁇ -aspartic acid.
  • neutral, cationic or anionic monomers such as, for example, ethylene oxide, propylene oxide, acrylic acid, maleic anhydride, N-vinylpyrrolidone, vinyl acetate, ⁇ - and ⁇ -aspartic acid.
  • Preferred protective colloids are compounds which are a cationic and biodegradable polymer, in particular a polymer having amino groups.
  • Particularly preferred protective colloids are selected from the group consisting of gelatin such as beef, pork and fish gelatin, plant proteins, casein, caseinate such as sodium caseinate, poly-L-lysine, poly-cysteine and proteins from the class of silaffins.
  • the protective colloid that forms the shell surrounding the core is a gelatin such as beef, pork and fish gelatin, casein or caseinate such as sodium caseinate.
  • the outer shell (shell 2) enclosing the protective colloid-containing shell (shell 1) contains at least one metal or semimetal oxide.
  • the outer shell (shell 2) is preferably more than 40 wt .-%, more preferably more than 70 wt .-%, in particular more than 85 wt .-% of at least one metal or Halbmetalloxid based on the mass the outer shell.
  • the percentage refers to a statistical average determined over a large number of particles.
  • the thickness of the outer metal or semimetal oxide-containing shell (shell 2) preferably has an average thickness of 1 nm to 200 nm, particularly preferably a thickness of 1 nm to 50 nm.
  • the average shell thickness refers not only to different values determined at different locations of the outer shell of a single particle, but also to the statistical average determined over a large number of particles.
  • Suitable metal or semimetal oxide are, in particular, those oxides which are sparingly soluble in water.
  • suitable Me- High or semi-metal oxides are TiO 2 , ZrO 2 , HfO 2 , Fe 2 O 3 , ZnO, Al 2 O 3 and SiO 2 .
  • Particularly preferred is silica (SiO 2 ), especially in the form of a silica gel.
  • the metal or semimetal oxides can be prepared by chemical reactions starting from suitable precursor compounds.
  • the various processes for the preparation of suitable metal oxides are known in principle to the person skilled in the art.
  • the particles of the invention having a core-shell-shell structure usually have an average particle size of from 5 nm to 20 000 nm, preferably from 10 to 1500 nm, in particular from 20 to 300 nm.
  • particles having a core-shell-shell structure in which
  • each particle comprises at least one fat-soluble vitamin or a carotenoid, in particular a carotenoid,
  • the shell (shell 1) directly surrounding each core comprises a gelatin, casein or caseinate, in particular gelatin, as protective colloid,
  • the outer shell (shell 2) enclosing the protective colloid-containing shell (shell 1) contains silica, in particular silica gel,
  • the core has an average particle size of 5 nm to 500 nm, especially 10 nm to 200 nm, and the average thickness of the outer shell is 1 nm to 200 nm, particularly 1 nm to 50 nm.
  • the content of silicon dioxide in the particles according to the invention after the dryer in the range of 10 to 20 wt .-% based on the total mass of the dried particles of the invention.
  • Another object of the present invention is also a process for the production of particles having a core-shell-shell structure, wherein
  • each particle located in the interior of each particle comprises at least one sparingly water-soluble or water-insoluble organic active substance
  • the shell (shell 1) directly surrounding each core comprises at least one protective colloid, which is a biodegradable polymer,
  • the outer shell (shell 2) enclosing the protective colloid-containing shell (shell 1) contains at least one metal or semimetal oxide
  • step iii) the metal or semimetal oxide is formed by a chemical reaction starting from a suitable precursor compound as an outer shell (shell 2).
  • the term dispersing is preferably understood to mean the preparation of aqueous suspensions and aqueous emulsions.
  • the dispersing step i) is particularly preferably the preparation of a suspension of at least one sparingly water-soluble or water-insoluble organic active ingredient in an aqueous molecular dispersion or colloidal disperse solution of a protective colloid, which is a biodegradable polymer in which the dispersed phase comprises at least one of the active compounds contains nanoparticulate particles.
  • a protective colloid which is a biodegradable polymer in which the dispersed phase comprises at least one of the active compounds contains nanoparticulate particles.
  • the nanodispersed phase in process step h) may be solid nanoparticles (suspension) or nanodroplets (emulsion).
  • the water-miscible solvents used in process step h) of the process according to the invention are, above all, water-miscible, thermally stable, volatile, only carbon, hydrogen and oxygen-containing solvents such as alcohols, ethers, esters, ketones and acetals.
  • solvents that are miscible with water at least 10% is used, have a boiling point below 200 0 C and / or have less than 10 carbon atoms.
  • Particular preference is given to using methanol, ethanol, n-propanol, isopropanol, 1, 2-butanediol 1-methyl ether, 1, 2-propanediol 1-n-propyl ether, tetrahydrofuran or acetone.
  • a water-immiscible organic solvent in the context of the present invention for an organic solvent having a water solubility at atmospheric pressure of less than 10%.
  • Possible solvents are, inter alia, halogenated aliphatic hydrocarbons, such as methylene chloride, chloroform and carbon tetrachloride, carboxylic acid esters such as dimethyl carbonate, diethyl carbonate, propylene carbonate, ethyl formate, methyl, ethyl or isopropyl acetate and ethers such as methyl tert. butyl ether in question.
  • Preferred water-immiscible organic solvents are the following compounds selected from the group consisting of dimethyl carbonate, propylene carbonate, ethyl formate, ethyl acetate, isopropyl acetate and methyl tert. butyl ether.
  • process step h) is preferably carried out, wherein the sparingly water-soluble or water-insoluble organic active substance, most preferably a carotenoid, in a water-miscible organic solvent or in a mixture of water and a water-miscible organic solvent at temperatures greater than 30 0 C, preferably between 50 0 C and 240 ° C, in particular 100 0 C to 200 ° C, particularly preferably 140 ° C to 180 0 C, optionally under pressure, is dissolved.
  • the sparingly water-soluble or water-insoluble organic active substance most preferably a carotenoid
  • elevated pressure for. B. in the range of 20 bar to 80 bar, preferably 30 to 60 bar, be advantageous.
  • the thus obtained molecular disperse solution is then mixed in process step h) directly with the optionally cooled aqueous molecular disperse or colloidal disperse solution of the protective colloid, which is a biodegradable polymer to form a hydrophobic phase containing the or the poorly water-soluble or water-insoluble organic active ingredients.
  • a mixture temperature of about 35 ° C. to 80 ° C. is preferably established.
  • Phase transferred and the hydrophobic phase of the poorly water-soluble or water-insoluble organic active ingredient is formed as a nanodisperse phase.
  • a further preferred embodiment of the process according to the invention is characterized in that the dispersion in process step i) is the preparation of a suspension, the or the sparingly water-soluble or water-insoluble organic active ingredients being in solid form and being ground in the presence of the protective colloid.
  • the grinding can be done in a conventional manner, for example with a ball mill. Depending on the type of mill used, it is ground until the particles have a mean particle size D [4,3] of 0.1 to 100 ⁇ m, preferably 0.2 to 50 ⁇ m, particularly preferably 0.2 to 20 ⁇ m, determined by Fraunhofer diffraction , very particularly preferably 0.2 to 5 .mu.m, in particular 0.2 to 0.8 microns have.
  • D [4,3] plots the volume-weighted mean diameter (see Malvern Mastersizer S manual, Malvern Instruments Ltd., UK).
  • the active ingredient-containing particles produced in process step i) and coated with protective colloid are optionally subjected to purification and / or isolation.
  • a purification method for example, the cross-flow filtration known to those skilled in the art (cross-flow filtration) or ultrafiltration can be used.
  • step iii) a dispersion of the protective colloid-coated particles prepared in step i) is provided and a metal or semimetal oxide-containing outer shell (shell 2) is formed around the dispersed particles, wherein the metal or semimetal oxide is replaced by a chemical Reaction starting from a suitable precursor compound as an outer shell (shell 2) is formed.
  • metal or semimetal oxide-containing layers are known in principle to the person skilled in the art.
  • a preferred method of forming these layers is the sol-gel method wherein a layer of a metal or semimetal hydroxide is first formed around the particles from a suitable starting compound which condenses directly to the metal or semimetal oxide with elimination of water.
  • the metal or semimetal hydroxides can be prepared, for example, from the corresponding metal or semimetal alkoxides, such as, for example, tetraisopropyl orthotitanate (Ti (O-iPropyl) 4) or tetramethyl orthosilicate (Si (O-Me) 4 ) by reaction with water or from alkali metal or alkaline earth silicate by adding acid.
  • the outer shell (shell 2) is preferably produced in process step iii) by reacting an aqueous solution of an alkali metal or alkaline earth silicate, preferably an alkali metal silicate such as sodium or potassium silicate, in particular sodium silicate, with an acid
  • an alkali metal silicate such as sodium or potassium silicate, in particular sodium silicate
  • an acid usually in the aqueous dispersion to form the outer shell (shell 2), a pH between 2 to 12, in particular between 4 to 9 is set.
  • Sulfuric acid or hydrochloric acid is preferably used for acidifying the aqueous alkali metal or alkaline earth metal silicate solution as acid, in particular using dilute sulfuric acid or dilute hydrochloric acid.
  • Process step iii) of the process according to the invention is usually carried out in a temperature range from 0 ° C. to 100 ° C., preferably in a temperature range from 10 ° C. to 60 ° C.
  • the dispersion is particularly preferred in the method according to the invention. Value of about 1 to 3 acidified.
  • the particles produced in process step iii) with a core-shell-shell structure are optionally purified and / or isolated.
  • the particles according to the invention with a core-shell-shell structure are characterized, inter alia, by the fact that they contain a high proportion of active ingredient, show improved stability to environmental influences such as temperature loads or atmospheric oxygen and / or enable the targeted setting of a delayed release behavior.
  • the particles of the invention having a core-shell-shell structure are suitable according to the encapsulated active ingredient as an additive to food preparations or animal feeds, as a constituent of cosmetic or pharmaceutical agents or as a constituent in crop protection preparations.
  • Another object of the present invention is the use of the particles with a core-shell-shell structure described above or which were prepared by the method described above, as an additive to animal feeds, foods, food supplements, cosmetics, pharmaceutical agents or pesticide preparation.
  • Another object of the present invention are powdered or liquid preparations comprising the above-described particles having a core-shell-shell structure or the particles produced by the method described above with a core-shell-shell structure.
  • the pulverulent or liquid preparations usually contain, in addition to the particles having a core-shell-shell structure, at least one of the customary additives and / or adjuvants which are familiar to the person skilled in the art for the respective field of application, for example in the animal feed, food and nutritional supplement sector Cosmetics or pharmaceutical agents or in the phytosanitary sector.
  • the present invention is the use of the above-described pulverulent or liquid preparations as an additive to animal feeds, foods, nutritional supplements, cosmetics, pharmaceutical agents or crop protection preparations.
  • a further subject of the present invention are animal feeds, foods, dietary supplements, cosmetics, pharmaceutical compositions or crop protection preparations containing the particles with a core-shell-shell structure which have been described above or which have been prepared according to the method described above.
  • Nanoparticles were examined for size, shape, and morphology by transmission electron microscopy (TEM).
  • the microscope was a Philips CM 120, which was operated at 120 kV.
  • different techniques of contrasting were used, which selectively contrasted one phase against the other, or the method of cryo-preparation was used, preserving the original states of the particles in the dispersion.
  • the widespread contrast with OsCu vapor was used for samples with beta-carotene because it contrasts double bonds and thus enhances the contrast between polymer and beta-carotene.
  • the samples were held over an open vessel containing volatile OsO 4 . The Os ⁇ 4 vapors penetrated the samples.
  • a beta-carotene / gelatin suspension (0.1 wt .-% beta-carotene based on the mass of the suspension) was prepared by means of mixing chamber micronization based on DE 31 19383, wherein THF as a water-soluble organic solvent was used. This suspension was washed by cross-flow filtration (ultrafiltration) to remove THF and excess gelatin and then concentrated. In cross-flow filtration, the suspension is pumped tangentially to a membrane, creating a pressure difference. Material which is smaller than the pore size of the membrane, passes in the process, the membrane as permeate or filtrate. Everything else remains in the flow as retentate. After concentration, a suspension containing about 1% by weight of beta-carotene was obtained. The core-shell structure of the beta-carotene / gelatin particles was detected by AFM. TEM was used to determine the morphology of the nanoparticles. The particles were spherical and their size was 10 to 100 nm.
  • gelatine of the type A was used.
  • gelatin of type B was used as gelatin.
  • Example 2 Preparation of beta-carotene / gelatin / silica particles from a beta-carotene / gelatin dispersion
  • a sodium silicate solution of concentration 25 mmol / L was prepared by adding at room temperature to 250 ml of deionized water a defined amount of a concentrated sodium silicate solution (6.25 mol / L, 27% SiO 2 , 10% NaOH, Riedel de Haaen) has been. Immediately after the preparation of the sodium silicate solution, it was poured into 250 ml of a beta-carotene / gelatin suspension (1%, pH 6-7) prepared in Example 1, whereby the pH of the mixture was brought to a pH of about 10 5 increase. The pH of the suspension was adjusted to a pH of about 7 by addition of dilute sulfuric acid (0.5 mol / L) or dilute hydrochloric acid (0.5 mol / L).
  • the mixture was gently stirred for 1 to 5 hours at room temperature.
  • the pH of the suspension did not change during the stirring time (pH 7).
  • dilute sulfuric acid (0.5 mol / L) or dilute hydrochloric acid (0.5 mol / L) was added and a pH of about 2 was adjusted.
  • the suspension was characterized by TEM (FIG. 1) and EDX (FIG. 2).
  • the core-shell structure was confirmed by TEM.
  • the size of the cores and shells was 20-100 nm and 5 nm, respectively.
  • the EDX measurement showed that the silica coated the surface of the beta-carotene / gelatin nanoparticles.
  • Electrophoretic measurements ( Figure 3) showed that the silica made the surface more negative.
  • the trace in a plot of mobility (Y-axis) vs. pH (X-axis) shifted to the left for the silica-layered particles, indicating that the isoelectric point shifted more into the acidic region.
  • beta-carotene / gelatin particles showed an isoelectric point at a pH of 7
  • the isoelectric point was at a pH of about 5.4. This means that the surface was charged more negatively, thus providing further evidence of successful silica coating.
  • Example 2a the particles produced in Example 1a) were coated with silica gel.
  • Example 2b the particles produced in Example 1 b) were coated with silica gel.
  • Table 1 show that under thermal stress the stability of silica-coated beta-carotene-containing particles increases compared to the beta-carotene cores coated with gelatin alone.
  • the numerical values represent the quotient of content of beta-carotene after a certain storage period to the original content of beta-carotene at the beginning of the respective test series.
  • Beta-carotene / gelatin and beta-carotene / gelatin / silica powder were used at room temperature.
  • the dissolution of beta-carotene / gelatin and beta-carotene / gelatin / silica in 500 ml of isopropanol was compared. After defined residence times of the samples in isopropanol, the concentration of beta-carotene in isopropanol was determined in each case. A delayed release of the beta-carotene sample with silica coating was observed. From Table 2 it can be seen that the dissolution of the beta-carotene was slowed down by the silica coating. The release of beta-carotene from sample 1a) was already finished after about 150 minutes. Because of the limited solubility of beta-carotene in isopropanol, the beta-carotene could not be completely released.
  • a suspension consisting of 5 g of Ethylhexyl Triazone (Uvinul ® T150), 5 g of gelatin B (100 Bloom) and 490 g of water was charged together with 100 g of zirconia beads (1 mm diameter) as grinding media in a 1 L glass bottle, and the bottle for a total of 4 hours at room temperature on a shaking apparatus intensively. It was ensured that the temperature of the suspension did not rise above 70 0 C.
  • Example 2 the milling balls were removed and a portion of the suspension was treated with a sodium silicate solution and acidified in the same manner as in Example 2 to obtain particles of ethylhexyl triazone, each directly surrounded by a gelatin shell surrounded by a silica shell , By means of dynamic light scattering, an average particle size of 200 nm was determined for the ethylhexyl triazone / gelatin / silica gel particles.
  • FIG. 1 depicts a TEM image of the beta carotene / gelatin / silica particles prepared in Example 2.
  • FIG. 2 illustrates an EDX spectrum of the beta-carotene / gelatin / silica particles prepared in Example 2 (X-axis: energy in keV, Y-axis: intensity).
  • FIG. 3 shows the electrophoretic characterization of the beta carotene / gelatin particles (BC / G) of Example 1 compared to the beta carotene / gelatin / silica particles (BC / G / Si) of Example 2, wherein the concentration of the conducting salt KCl was 10 mmol / L, the pH value was adjusted with aqueous hydrochloric acid or dilute aqueous NaOH solution, the mobility ⁇ e in the Y-axis is given in ( ⁇ m / s) / (V / cm) and on the X -Axis of the pH value is indicated.

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Abstract

La présente invention concerne des particules avec une structure noyau-enveloppe-enveloppe. Le noyau se trouvant à l'intérieur de chaque particule comprend au moins une substance organique difficilement soluble dans l'eau ou insoluble dans l'eau. L'invention concerne également un procédé de production de ces particules avec une structure noyau-enveloppe-enveloppe et des préparations contenant les particules avec la structure noyau-enveloppe-enveloppe.
PCT/EP2009/057369 2008-06-16 2009-06-15 Particules contenant une substance active Ceased WO2010003762A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP08158302 2008-06-16
EP08158302.3 2008-06-16

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US20160184196A1 (en) * 2014-12-16 2016-06-30 The Procter & Gamble Company Compositions Providing Delayed Release of Actives
WO2017134524A3 (fr) * 2016-02-01 2017-09-28 I2O Pharma Ltd. Microcapsules sphériques ayant une meilleure biodisponibilité orale
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CN110099743A (zh) * 2016-12-22 2019-08-06 弗门尼舍有限公司 具有矿物层的微胶囊
CN111801155A (zh) * 2018-06-21 2020-10-20 弗门尼舍有限公司 制备微胶囊的方法
CN111886071A (zh) * 2018-06-21 2020-11-03 弗门尼舍有限公司 制备矿化的微胶囊的方法
WO2021116432A1 (fr) 2019-12-12 2021-06-17 Papierfabrik August Koehler Se Systèmes de microcapsule biodégradable
WO2021115600A1 (fr) 2019-12-12 2021-06-17 Henkel Ag & Co. Kgaa Agents de lavage et de nettoyage comprenant des microcapsules écologiquement compatibles
EP4101528A1 (fr) 2021-06-11 2022-12-14 Henkel AG & Co. KGaA Milieu contenant des microcapsules dégradables de couleur neutre
EP4101529A1 (fr) 2021-06-11 2022-12-14 Henkel AG & Co. KGaA Milieu contenant des microcapsules dégradables de couleur neutre avec composition de parfum
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DE102021214457A1 (de) 2021-12-15 2023-06-15 Koehler Innovation & Technology Gmbh Mikrokapseldispersionen mit Emulgator
EP4198113A1 (fr) 2021-12-15 2023-06-21 Henkel AG & Co. KGaA Milieu contenant un émulsifiant et des microcapsules
EP4198114A1 (fr) 2021-12-15 2023-06-21 Henkel AG & Co. KGaA Agent contenant un émulsifiant et des microcapsules
EP4198115A1 (fr) 2021-12-15 2023-06-21 Henkel AG & Co. KGaA Milieu contenant un émulsifiant et des microcapsules comportant des composition de parfum

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KR101960369B1 (ko) 2011-12-28 2019-03-21 엘지디스플레이 주식회사 전기영동 표시소자 및 그 제조 방법
KR20130076200A (ko) * 2011-12-28 2013-07-08 엘지디스플레이 주식회사 전기영동 입자 및 그를 이용한 전기영동 표시소자 및 그 제조 방법
EP2689836A1 (fr) * 2012-07-26 2014-01-29 Basf Se Composition de microcapsules présentant une enveloppe de silice et un procédé pour leur préparation
WO2014016367A1 (fr) 2012-07-26 2014-01-30 Basf Se Composition de microcapsules à enveloppe de silice et procédé pour leur préparation
EP2868628A1 (fr) 2013-10-30 2015-05-06 Basf Se Procédé de préparation d'une composition de dioxyde de silicium
CN107001979A (zh) * 2014-12-16 2017-08-01 宝洁公司 包衣微胶囊
CN107107019A (zh) * 2014-12-16 2017-08-29 宝洁公司 包衣微胶囊
US20160177221A1 (en) * 2014-12-16 2016-06-23 The Procter & Gamble Company Coated Microcapsules
WO2016100499A1 (fr) * 2014-12-16 2016-06-23 The Procter & Gamble Company Microcapsules enrobées
WO2016100479A1 (fr) * 2014-12-16 2016-06-23 The Procter & Gamble Company Microcapsules enrobées
US20160184196A1 (en) * 2014-12-16 2016-06-30 The Procter & Gamble Company Compositions Providing Delayed Release of Actives
CN106999896A (zh) * 2014-12-16 2017-08-01 宝洁公司 包衣微胶囊
CN106999896B (zh) * 2014-12-16 2020-10-30 诺赛尔股份有限公司 包衣微胶囊
CN106999895A (zh) * 2014-12-16 2017-08-01 宝洁公司 包衣微胶囊
US20160168510A1 (en) * 2014-12-16 2016-06-16 The Procter & Gamble Company Coated Microcapsules
US20160168511A1 (en) * 2014-12-16 2016-06-16 The Procter & Gamble Company Coated Microcapsules
US9944886B2 (en) 2014-12-16 2018-04-17 Noxell Corporation Coated microcapsules
US9944887B2 (en) 2014-12-16 2018-04-17 Noxell Corporation Coated microcapsules
US9951293B2 (en) 2014-12-16 2018-04-24 Noxell Corporation Coated microcapsules
US9951294B2 (en) 2014-12-16 2018-04-24 Noxell Corporation Coated microcapsules
US9962321B2 (en) 2014-12-16 2018-05-08 Noxell Corporation Compositions providing delayed release of actives
EP3888782A1 (fr) * 2014-12-16 2021-10-06 Noxell Corporation Microcapsules revêtues
US20160168509A1 (en) * 2014-12-16 2016-06-16 The Procter & Gamble Company Coated Microcapsules
CN107001979B (zh) * 2014-12-16 2021-05-28 诺赛尔股份有限公司 包衣微胶囊
WO2017134524A3 (fr) * 2016-02-01 2017-09-28 I2O Pharma Ltd. Microcapsules sphériques ayant une meilleure biodisponibilité orale
JP2020515380A (ja) * 2016-12-22 2020-05-28 フイルメニツヒ ソシエテ アノニムＦｉｒｍｅｎｉｃｈ Ｓａ 無機質層を有するマイクロカプセル
JP7078629B2 (ja) 2016-12-22 2022-05-31 フイルメニツヒ ソシエテ アノニム 無機質層を有するマイクロカプセル
CN110099743A (zh) * 2016-12-22 2019-08-06 弗门尼舍有限公司 具有矿物层的微胶囊
CN110099743B (zh) * 2016-12-22 2022-06-14 弗门尼舍有限公司 具有矿物层的微胶囊
US11135561B2 (en) 2016-12-22 2021-10-05 Firmenich Sa Microcapsules having a mineral layer
WO2018115330A1 (fr) * 2016-12-22 2018-06-28 Firmenich Sa Microcapsules à couche minérale
CN111886071A (zh) * 2018-06-21 2020-11-03 弗门尼舍有限公司 制备矿化的微胶囊的方法
US12138610B2 (en) 2018-06-21 2024-11-12 Firmenich Sa Process for preparing mineralized microcapsules
CN111886071B (zh) * 2018-06-21 2023-10-27 弗门尼舍有限公司 制备矿化的微胶囊的方法
CN111801155A (zh) * 2018-06-21 2020-10-20 弗门尼舍有限公司 制备微胶囊的方法
WO2021115600A1 (fr) 2019-12-12 2021-06-17 Henkel Ag & Co. Kgaa Agents de lavage et de nettoyage comprenant des microcapsules écologiquement compatibles
WO2021115601A1 (fr) 2019-12-12 2021-06-17 Papierfabrik August Koehler Se Systèmes de microcapsules biodégradables
WO2021116365A1 (fr) 2019-12-12 2021-06-17 Henkel Ag & Co. Kgaa Agents de lavage et de nettoyage comprenant des microcapsules écologiquement compatibles
WO2021116432A1 (fr) 2019-12-12 2021-06-17 Papierfabrik August Koehler Se Systèmes de microcapsule biodégradable
EP4101528A1 (fr) 2021-06-11 2022-12-14 Henkel AG & Co. KGaA Milieu contenant des microcapsules dégradables de couleur neutre
EP4101529A1 (fr) 2021-06-11 2022-12-14 Henkel AG & Co. KGaA Milieu contenant des microcapsules dégradables de couleur neutre avec composition de parfum
WO2022258808A1 (fr) 2021-06-11 2022-12-15 Henkel Ag & Co. Kgaa Compositions contenant des microcapsules dégradables neutres en couleur
WO2022258118A1 (fr) 2021-06-11 2022-12-15 Koehler Innovation & Technology Gmbh Microcapsules dégradables de couleur neutre
DE102021205957A1 (de) 2021-06-11 2022-12-15 Koehler Innovation & Technology Gmbh Farbneutrale abbaubare Mikrokapseln
DE102021214457A1 (de) 2021-12-15 2023-06-15 Koehler Innovation & Technology Gmbh Mikrokapseldispersionen mit Emulgator
EP4198115A1 (fr) 2021-12-15 2023-06-21 Henkel AG & Co. KGaA Milieu contenant un émulsifiant et des microcapsules comportant des composition de parfum
WO2023110035A1 (fr) 2021-12-15 2023-06-22 Koehler Innovation & Technology Gmbh Dispersions de microcapsules avec émulsifiant
EP4198114A1 (fr) 2021-12-15 2023-06-21 Henkel AG & Co. KGaA Agent contenant un émulsifiant et des microcapsules
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