# US 2014/0154324 A1 · Agglomerating magnetic alkoxysilane-coated nanoparticles

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0154324 A1
- Document ID: US20140154324A1
- Status: Published application
- Kind: A1
- Application number: 13/877,891
- Filed: 2012-08-07
- Published: 2014-06-05
- Earliest claimed: 2011-08-10
- Assignees: Magforce AG
- Inventors: Norbert Waldöfner; Andreas Jordan
- Web page: https://patentgrep.com/patent/US20140154324A1

## CPC

- A61K 41/0052: {Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy}
- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- H01F 1/0054: {Coated nanoparticles, e.g. nanoparticles coated with organic surfactant}
- H01F 41/16: the magnetic material being applied in the form of particles, e.g. by serigraphy {, to form thick magnetic films or precursors therefor} (H01F41/18 {-H01F41/24} take precedence)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- H01F: MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES

## Abstract

The present invention relates to a method for producing a suspension of agglomerates of magnetic alkoxysilane-coated metal nanoparticles, wherein an aqueous suspension of magnetic metal nanoparticles is incubated with alkoxysilane, wherein the incubation is carried out essentially in the absence of an organic solvent. The present invention further relates to suspension of agglomerates of magnetic alkoxysilane-coated metal containing nanoparticles obtainable by the method of the present invention and to a composition comprising agglomerates of magnetic alkoxysilane-coated metal nanoparticles, wherein the agglomerates have an average size of 30 to 450 nm, preferably of 50 to 350 nm and especially of 70 to 300 nm as determined by light scattering.

## Claims

### Claim 1

A method for producing a suspension of agglomerates of magnetic alkoxysilane-coated metal nanoparticles, wherein an aqueous suspension of magnetic metal nanoparticles is incubated with alkoxysilane,
characterized in that said incubation is carried out essentially in the absence of an organic solvent.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the metal nanoparticles comprise iron, iron complex compounds, iron carbonyl compounds or iron salts, preferably iron salts.

### Claim 3 (depends on 2)

The method according to claim 2, wherein the iron salt is an iron oxide, preferably magnetite and/or maghemite.

### Claim 4 (depends on 3)

The method according to the claim 3, wherein the aqueous suspension of iron oxide nanoparticles is
a) provided by precipitating a solution containing a mixture of iron(III) chloride and iron(II) chloride with sodium hydroxide, or
b) by thermal decomposition of an iron salt or an iron complex compound.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the magnetic metal nanoparticles are treated with H2O2 prior to the incubation.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the alkoxysilane is a trialkoxysilane, preferably selected from the group consisting of 3-(2-aminoethylamino)-propyl-trimethoxysilane, 3-aminopropyltriethoxysilane, trimethoxysilylpropyl-diethylenetriamine and N-(6-aminohexyl)-3-aminopropyltrimethoxysilane, especially 3-(2-aminoethylamino)-propyl-trimethoxysilane.

### Claim 7 (depends on 1)

The method according to claim 1, wherein 0.3 to 0.6×10−3 mol, preferably 0.4 to 0.5×10−3 mol and especially 0.43 to 0.45×10−3 mol trialkoxysilane is added per 0.9 mol metal.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the incubation is performed at a pH between 2 and 6.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the metal magnetic nanoparticles are disintegrated prior to the incubation with alkoxysilane.

### Claim 10 (depends on 1)

The method according to claim 1, further comprising the step of disintegrating the magnetic nanoparticles after starting the incubation with alkoxysilane.

### Claim 11 (depends on 1)

The method according to claim 1, further comprising the step of removing incompletely coated nanoparticles.

### Claim 12 (depends on 9)

The method according to claim 9, wherein the agglomerates are disintegrated until an average size of 30 to 450 nm, preferably of 50 to 350 nm and especially of 70 to 300 nm as determined by light scattering is achieved.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the suspension of agglomerates is concentrated to a concentration of at least about 2 M, preferably of at least about 3 M, more preferably of at least about 4 M, even more preferably of at least about 5 M, and especially of at least about 6 M as determined by its metal content.

### Claim 14 (depends on 1)

A suspension of agglomerates of magnetic alkoxysilane-coated metal containing nanoparticles obtained by a method according to claim 1.

### Claim 15

A composition comprising agglomerates of magnetic alkoxysilane-coated metal nanoparticles, wherein the agglomerates have an average size of 30 to 450 nm, preferably of 50 to 350 nm and especially of 70 to 300 nm as determined by light scattering.

### Claim 16 (depends on 15)

The composition according to claim 15, wherein the composition is essentially free of organic solvents.

### Claim 17 (depends on 15)

The composition according to claim 15, wherein the metal nanoparticles have a metal core with a size of 5 to 25 nm, preferably 7 to 20 nm and especially 9 to 15 nm as determined by electron microscopy.

### Claim 18 (depends on 15)

The composition according to claim 15, wherein the metal nanoparticles comprise iron, iron complex compounds, iron carbonyl compounds or iron salts, preferably iron salts.

### Claim 19 (depends on 15)

The composition according to claim 15, wherein the zeta potential of the metal nanoparticles is 25 to 80 mV, preferably 35 to 70 mV, especially 45 to 60 mV, at pH 5.2 and a conductivity of 2.0 mS/cm.

### Claim 20 (depends on 15)

The composition according to claim 15, wherein the agglomerates are suspended in a water-based physiologically acceptable buffer.

### Claim 21 (depends on 20)

The composition according to claim 20, wherein the nanoparticles have a concentration of at least about 2 M, preferably of at least about 3M, more preferably of at least about 4 M, more preferably of at least about 5 M and especially of at least about 6 M, as determined by metal content.

### Claim 22 (depends on 20)

The composition according to claim 20, wherein the viscosity of the suspension at a shear rate of 100/s is equal or more than 0.005 Pa s, preferably equal or more than 0.01 Pa s, more preferably equal or more than 0.1 Pa s, and especially equal or more than 1 Pa s, as determined by rotational rheometry.

### Claim 23 (depends on 20)

The composition of claim 20, wherein the specific absorption rate (SAR) of the nanoparticles in suspension is larger or equal than 2 W/g Me, preferably larger or equal than 3 W/g Me and especially 4 to 12 W/g Me as determined at a magnetic field strength of 3.5 kA/m and a frequency of 100 kHz.

### Claim 24 (depends on 20)

The composition of claim 20, wherein upon injection of the suspension into an isogen tumor model at or after day 7 after the injection at least 90%, preferably at least 93%, more preferably at least 95%, and especially at least 98% of applied metal remains within the injected tumor.

### Claim 25 (depends on 20)

The composition of claim 20, obtained by a method comprising a method for producing a suspension of agglomerates of magnetic alkoxysilane-coated metal nanoparticles, wherein an aqueous suspension of magnetic metal nanoparticles is incubated with alkoxysilane, characterized in that said incubation is carried out essentially in the absence of an organic solvent.

### Claim 26 (depends on 14)

Medical device comprising the suspension of claim 14 or a composition comprising agglomerates of magnetic alkoxysilane-coated metal nanoparticles, wherein the agglomerates have an average size of 30 to 450 nm, preferably of 50 to 350 nm and especially of 70 to 300 nm as determined by light scattering.

### Claim 27 (depends on 14)

Medicament comprising the suspension of claim 14 or a composition comprising agglomerates of magnetic alkoxysilane-coated metal nanoparticles, wherein the agglomerates have an average size of 30 to 450 nm, preferably of 50 to 350 nm and especially of 70 to 300 nm as determined by light scattering.

### Claim 28

(canceled)

### Claim 29 (depends on 14)

Method of treating or preventing proliferative disease, cancer, tumors, rheumatism, arthritis, arthrosis and bacterial infections comprising the step of administering the suspension of claim 14 or a composition comprising agglomerates of magnetic alkoxysilane-coated metal nanoparticles, wherein the agglomerates have an average size of 30 to 450 nm, preferably of 50 to 350 nm and especially of 70 to 300 nm as determined by light scattering, to a human or animal patient.

### Claim 30 (depends on 29)

The method of claim 29, wherein said method further includes exposing the patient to an alternating magnetic field.