ES2582283T3 - Dispositivo médico que comprende aglomerados de nanopartículas magnéticas recubiertas con alcoxisilano - Google Patents

Dispositivo médico que comprende aglomerados de nanopartículas magnéticas recubiertas con alcoxisilano

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Publication number
ES2582283T3
ES2582283T3 ES12748166.1T ES12748166T ES2582283T3 ES 2582283 T3 ES2582283 T3 ES 2582283T3 ES 12748166 T ES12748166 T ES 12748166T ES 2582283 T3 ES2582283 T3 ES 2582283T3
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Spain
Prior art keywords
alkoxysilane
agglomerates
medical device
nanoparticles coated
magnetic nanoparticles
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ES12748166.1T
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English (en)
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Norbert WALDÖFNER
Andreas Jordan
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Magforce AG
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Magforce AG
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/26—Iron; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/695—Silicon compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
    • H01F1/0036—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties showing low dimensional magnetism, i.e. spin rearrangements due to a restriction of dimensions, e.g. showing giant magnetoresistivity
    • H01F1/0045—Zero dimensional, e.g. nanoparticles, soft nanoparticles for medical/biological use
    • H01F1/0054—Coated nanoparticles, e.g. nanoparticles coated with organic surfactant
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F41/00—Apparatus or processes specially adapted for manufacturing or assembling magnets, inductances or transformers; Apparatus or processes specially adapted for manufacturing materials characterised by their magnetic properties
    • H01F41/14—Apparatus or processes specially adapted for manufacturing or assembling magnets, inductances or transformers; Apparatus or processes specially adapted for manufacturing materials characterised by their magnetic properties for applying magnetic films to substrates
    • H01F41/16—Apparatus or processes specially adapted for manufacturing or assembling magnets, inductances or transformers; Apparatus or processes specially adapted for manufacturing materials characterised by their magnetic properties for applying magnetic films to substrates the magnetic material being applied in the form of particles, e.g. by serigraphy, to form thick magnetic films or precursors therefor

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Nanotechnology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Power Engineering (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Inorganic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Oncology (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Manufacturing & Machinery (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Compounds Of Iron (AREA)
  • Soft Magnetic Materials (AREA)
  • Hard Magnetic Materials (AREA)
  • Manufacture Of Metal Powder And Suspensions Thereof (AREA)
  • Powder Metallurgy (AREA)
  • Electrotherapy Devices (AREA)

Abstract

Un dispositivo médico que comprende una suspensión de aglomerados de nanopartículas de metal magnético recubiertas con alcoxisilano, en donde una suspensión acuosa de nanopartículas de metal magnético se incuba con alcoxisilano, caracterizado porque la incubación se realiza esencialmente en ausencia de un solvente orgánico añadido, el alcoxisilano es trialcoxisilano y se añaden 0,3 a 0,6 x 10-3 mol de trialcoxisilano por 0,9 mol de metal.

Description

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Una suspensión 2 M de nanopartículas de óxido de hierro magnético fabricada de acuerdo con el Ejemplo 1 ha sido analizada por TEM. La micrografía resultante se muestra en la Figura 1. En la micrografía, se pueden ver grandes aglomerados de nanopartículas (una nanopartícula individual indicada por una flecha). No se pueden observar nanopartículas individuales dentro del área representada -todas las nanopartículas están unidas entre sí.
7. Especificaciones de la suspensión
Una serie de producción de acuerdo con el ejemplo 1 conduce a las especificaciones físicas/químicas como se muestran en la Tabla 2.
Tabla 2: Especificaciones de una carga representativa
AS1
AS4 AS5
Tamaño de la partícula (promedio z)
89 nm 179,6 180,8 nm
Potencial zeta
53,5 mV 47,8 mV 42,5 mV
Conductividad (25 °C)
2,16 ms/cm 0,90 ms/cm -
pH (25 °C)
5,28 4,38 --
Osmolalidad
0,03 Osmol/kg 0,08 Osmol/kg --
SAR (a 100 kHz, a intensidad del campo dada)
10 W/g Fe (7,5 kA/m) 14 W/g Fe (4 kA/m) 12 W/g Fe (6 kA/m)
Contenido del metal total (Fe)
15% por peso 18% por peso --
Concentración (Fe)
1,99 mol/l 1,70 mol/l 1,88 mol/l
10 8. Reometría de rotación/Medición de la viscosidad
La viscosidad de las muestras de nanopartículas se determinó por servicios de caracterización de materiales Malvern usando reometría de rotación a 20 °C, en donde la viscosidad de cizallamiento (en Pa.s) se determinó en dependencia de la velocidad de cizallamiento (de 7 a 1500/s). Los resultados para preparaciones de nanopartículas de acuerdo con el Ejemplo 1 se muestran en la Figura 2.
15 9. Formación de depósitos de fluidos magnéticos in vivo
Se inyectaron 1x106 células tumorales de la línea celular de carcinoma mamario C3H RSI en la extremidad posterior derecha de los ratones de la cepa C3H-HeN (Harlan Laboratories, Borchen). Una vez que los tumores inducidos tenían un volumen de 0,57-0,85 cm3, los animales fueron asignados al azar (15 animales por grupo) y los tumores de la extremidad posterior derecha fueron inyectados con el fluido magnético del Ejemplo 1 que tiene una concentración
20 de Fe de 112 o 335 mg/ml. El contenido exacto del volumen de inyección se determinó pesando la jeringa de inyección antes y después de la inyección y calculando la diferencia (en promedio, 31 µl ± 5,8 µl).
El contenido de Fe total de tejido/tumor de los ratones se determinó después de 0 o 7 días de medición UV-vis a 565 nm utilizando la prueba de Spektroquant 14761 (Merck, Darmstadt) y un Cary 50 (Agilent Technologies, Santa Clara, Ca, USA) y un espectrómetro Tecan Infinite M 200 (Tecan Group Ltd, Männedorf, Suiza). El contenido de Fe
25 aplicado inicialmente se determinó restando del contenido de Fe total del contenido del tejido/tumor inicial del tejido (determinado midiendo el contenido de Fe de la pata izquierda no inoculada) y la pérdida de fluido magnético durante la inoculación, que fue absorbida por el hisopo utilizado. La recuperación de Fe (promedio de 15 tumores por grupo) se calculó como el contenido total de Fe, dividido por el contenido de Fe aplicado inicialmente.
13
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Thiesen, B. and A. Jordan (2008). Int J Hyperthermia. 24(6): 467-74. Waldoefher, N. and K. Stief (201 1). Magnetic Transducers. US 201 1/0052609.
16

Claims (1)

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    imagen2
ES12748166.1T 2011-08-10 2012-08-07 Dispositivo médico que comprende aglomerados de nanopartículas magnéticas recubiertas con alcoxisilano Active ES2582283T3 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161522217P 2011-08-10 2011-08-10
US201161522217P 2011-08-10
PCT/EP2012/003381 WO2013020701A2 (en) 2011-08-10 2012-08-07 Agglomerating magnetic alkoxysilane-coated nanoparticles

Publications (1)

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ES12748166.1T Active ES2582283T3 (es) 2011-08-10 2012-08-07 Dispositivo médico que comprende aglomerados de nanopartículas magnéticas recubiertas con alcoxisilano

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US (2) US9408912B2 (es)
EP (2) EP2742515B1 (es)
JP (1) JP5844902B2 (es)
KR (1) KR101513841B1 (es)
CN (1) CN104620334B (es)
AU (1) AU2012292554B2 (es)
BR (1) BR112014002726A8 (es)
CA (1) CA2844774C (es)
CL (1) CL2014000298A1 (es)
CO (1) CO6940414A2 (es)
DE (1) DE202012012795U1 (es)
DK (1) DK2742515T3 (es)
ES (2) ES2807209T3 (es)
HK (1) HK1210317A1 (es)
IL (1) IL230799A (es)
MX (1) MX358576B (es)
PL (2) PL2742515T3 (es)
PT (1) PT2742515T (es)
RU (1) RU2622025C2 (es)
WO (1) WO2013020701A2 (es)
ZA (1) ZA201400564B (es)

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