# US 8,771,699 B2 · Magnetic transducers

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- Number: US 8,771,699 B2
- Document ID: US8771699B2
- Status: Granted
- Kind: B2
- Application number: 12/738,970
- Filed: 2009-01-09
- Published: 2011-03-03
- Granted: 2014-07-08
- Earliest claimed: 2008-01-09
- Assignees: Magforce AG
- Applicants: Norbert Waldoefner; Kerstin Stief
- Inventors: Norbert Waldoefner; Kerstin Stief
- Web page: https://patentgrep.com/patent/US8771699B2

## CPC

- A61K 9/143: {with inorganic compounds}
- A61K 33/26: Iron; Compounds thereof
- A61K 41/0052: {Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- B82Y 30/00: Nanotechnology for materials or surface science, e.g. nanocomposites
- C01G 49/02: Oxides; Hydroxides {(C01G49/0018 takes precedence)}
- C01G 49/06: Ferric oxide [Fe2O3]
- C01G 49/08: Ferroso-ferric oxide [Fe3O4]
- C09C 1/24: Oxides of iron
- C01P 2004/42: (bi)pyramid-like
- C01P 2004/64: Nanometer sized, i.e. from 1-100 nanometer
- 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
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- C01G: COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F (metal hydrides {monoborane, diborane or addition complexes thereof} C01B6/00; salts of oxyacids of halogens C01B11/00; peroxides, salts or peroxyacids C01B15/00; thiosulfates, dithionites, polythionates C01B17/64; compounds containing selenium, or tellurium C01B19/00; binary compounds of nitrogen with metals C01B21/06; azides C01B21/08; {compounds containing nitrogen, other non-metals and metal C01B21/082}; metal amides C01B21/092; nitrites C01B21/50; {compounds of noble gases C01B23/0005}; phosphides C01B25/08; salts of oxyacids of phosphorus C01B25/16; carbides C01B32/90; compounds containing silicon C01B33/00; compounds containing boron C01B35/00; compounds having molecular sieve properties but not having base-exchange properties C01B37/00; compounds having molecular sieve and base-exchange properties, e.g. crystalline zeolites, C01B39/00; cyanides C01C3/08; salts of cyanamide C01C3/16; thiocyanates C01C3/20)
- C09C: TREATMENT OF INORGANIC MATERIALS, OTHER THAN FIBROUS FILLERS, TO ENHANCE THEIR PIGMENTING OR FILLING PROPERTIES (treatment of materials specially adapted to enhance their filling properties in mortars, concrete or artificial stone C04B14/00, C04B18/00, C04B20/00); PREPARATION OF CARBON BLACK {; PREPARATION OF INORGANIC MATERIALS WHICH ARE NO SINGLE CHEMICAL COMPOUNDS AND WHICH ARE MAINLY USED AS PIGMENTS OR FILLERS}
- C01P: INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS

## Abstract

Embodiments herein relate to the production of biocompatible magnetic nanoparticles with a high SAR-value which produce a large amount of heat when exposed to an alternating magnetic field. The produced heat can be used among others for therapeutic purposes, in particular for combating cancer.

## Claims

### Claim 1

A method for the production of nanoparticles comprising the following steps:
A1) providing a composition of at least one iron-containing compound A in at least one organic solvent LM1, wherein the at least one iron-containing compound A is selected from the group consisting of iron complex compounds, iron carbonyl compounds, iron salts, organic iron compounds, and iron-sandwich-complexes, and wherein the at least one organic solvent LM1 is a high boiling solvent;
B1) heating of the composition to a temperature in the range of 50° C. to a temperature of 50° C. below the actual reaction temperature of the iron-containing compound A according to step C1 for a minimum period of 10 minutes;
C1) heating of the composition to an actual reaction temperature between 200° C. and 400° C. to obtain particles, wherein the heating step is carried out for at least 30 minutes;
D1) purifying the obtained particles, wherein the purification is performed by Soxhlet extraction;
E1) suspending the particles in water or an aqueous solution of an acid;
F1) adding a surface-active compound;
I1) producing a dispersion of the particles in a solvent mixture of (i) water and (ii) a solvent miscible with water; and
J1) adding an alkoxysilane to the dispersion of the particles in the solvent mixture according to step I1);
wherein the method further comprising step X2) following steps C1 or E1 or F1 or I1 or J1: X2) oxidizing the formed particles by suspending the particles in 0.5 to 2M HNO3, adding an Fe(III) salt and boiling the particles under reflux; and
wherein the nanoparticles have a specific absorption rate (SAR) of 10-40 W per g Fe at a field strength of 4 kA/m and at frequency of an alternating magnetic field of 100 kHz.

### Claim 2 (depends on 1)

The method according to claim 1, further comprising step A2) following step A1:
A2) adding an additive selected from the group consisting of: tensides, silanes, Si- or Al-containing organic compounds, phosphines, saturated or unsaturated fatty acids, amines, diamines, carboxylic acids and salts thereof, saturated and unsaturated fatty acids, and polymers.

### Claim 3 (depends on 1)

The method according to claim 1, further comprising step B2) following step B1:
B2) adding an additive selected from the group consisting of: tensides, silanes, Si- or Al-containing organic compounds, phosphines, saturated or unsaturated fatty acids, amines, diamines, carboxylic acids and salts thereof, saturated and unsaturated fatty acids, and polymers,
or
B2) adding a composition of at least one iron-containing compound B in at least one organic solvent LM2, wherein the at least one iron-containing compound B is selected from the group consisting of: iron complex compounds, iron carbonyl compounds, iron salts, organic iron compounds, and iron-sandwich-complexes, and wherein the at least one organic solvent LM2 is a high boiling solvent, or
B2) adding a composition of at least one iron-containing compound B in at least one organic solvent LM2, and addition of an additive selected from the group consisting of: tensides, silanes, Si- or M-containing organic compounds, phosphines, saturated or unsaturated fatty acids, amines, diamines, carboxylic acids and salts thereof, saturated and unsaturated fatty acids, and polymers.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the at least one solvent LM2 has a minimum boiling point of 200° C.

### Claim 5 (depends on 3)

The method according to claim 3, wherein the at least one solvent LM2 is selected from the group consisting of: high-boiling amines, alkanes, olefms, alcohols or ethers, alkylene glycol monoethers, alkylene glycol diethers, ethylene glycol monoethers, ethylene glycol diethers, propylene glycol monothers, propylene glycol diethers, glycerin monoethers, glycerin diethers, glycerin triethers, and glycol diethers (glymes).

### Claim 6 (depends on 3)

The method according to claim 3, wherein the at least one iron-containing compound B is identical to the at least one iron-containing compound A and/or the at least one organic solvent LM1 is identical to the at least one organic solvent LM2.

### Claim 7 (depends on 1)

The method according to claim 1, further comprising a tempering step D1*) following step D1:
D1*) tempering of the obtained particles in high boiling solvents at up to 400° C. for 1-30 hours.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the at least one iron-containing compound A is selected from the group consisting of: iron complex compounds, iron carbonyl compounds, iron salts, organic iron compounds, iron salts of saturated/unsaturated fatty acids and iron-sandwich-complexes.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the at least one solvent has a minimum boiling point of 200° C.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the at least one solvent LM1 is selected from the group consisting of: high-boiling amines, alkanes, olefins, alcohols, ethers, alkylene glycol-monoethers, alkylene glycol-diethers, ethylene glycol-monoethers, ethylene glycol- diethers, propylene glycol-monothers, propylene glycol diethers, glycerin monoethers, glycerin diethers, glycerin triethers, and glycol diethers (glymes).

### Claim 11 (depends on 1)

The method according to claim 1, wherein the aqueous solution of the acid has a pH of 2 to 6.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the acid according to step E1) is a mineral acid selected from the group consisting of: hydrochloric acid, phosphoric acid, sulfuric acid, bromhydric acid, boric acid and nitric acid.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the surface-active compound according to step F1) is selected from the group consisting of: fatty acids, fatty acid salts, tensides, polymers, polyvinyl alcohol, polyethylene glycol, polyacrylic acid, dextran, PLGA, chitosan and polyethylene imine.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the solvent mixture according to step I1) is an alcohol-water mixture with a volume ratio of alcohol to water ranging from 1:1 to 1:5.

### Claim 15 (depends on 14)

The method according to claim 14, wherein the solvent mixture further comprises an amine or ammonia.

### Claim 16 (depends on 14)

The method according to claim 14, wherein the alcohol is selected from the group consisting of: methanol, ethanol, propanol and isopropanol.

### Claim 17 (depends on 1)

The method according to claim 1, wherein the alkoxysilane according to step J1) is selected from the group consisting of: tetraalkoxysilanes, trialkoxysilanes, dialkoxysilanes and monoalkoxysilanes.

### Claim 18 (depends on 1)

The method according to claim 1, wherein the molar ratio of particle to alkoxysilane according to step J1) ranges from 1:1 to 1:5.

### Claim 19 (depends on 1)

The method according to claim 1, wherein the alkoxysilane according to step J1) is added under ultrasonic treatment.

### Claim 20 (depends on 1)

The method according to claim 1, wherein the dispersion obtained according to claim J1) is treated with ultrasound for 1 to 8 hours.

### Claim 21 (depends on 1)

The method according to claim 1, further comprising step L1):
L1) Coupling of an anticancer compound, a monoclonal antibody, an aptamer, a nucleic acid, an amino acid, a peptide, a protein, a carbohydrate, a lipid, a glycoprotein, a glycan, a lipoprotein, or of an anti-proliferative, anti-migrative, anti-angiogenic, anti-thrombotic, anti-inflammatory, anti-phlogistic, cytostatic, cytotoxic, anti-coagulative, anti-bacterial, anti-viral, or anti-mycotic drug to the particles obtained.

### Claim 22 (depends on 1)

The method according to claim 1, further comprising a tempering step D2*) following step X2:
D2*) tempering of the obtained particles.

### Claim 23 (depends on 1)

The method according to claim 1, further comprising step G1) following step F1: G1) treating the aqueous solution according to step F1) with ultrasound.

### Claim 24 (depends on 23)

The method according to claim 23, further comprising step H1) following step G1: H1) purifying the aqueous dispersion of the particles obtained according to step G1.

### Claim 25 (depends on 1)

The method according to claim 1, further comprising step K1) following step J1: K1) purifying of the particles.

### Claim 26 (depends on 1)

The method according to claim 1, further comprising:
(a) step D1) following step C1: D1) purifying the obtained particles;
(b) step G1) following step F1: G1) treating the aqueous solution according to step F1) with ultrasound;
(c) step H1) following step G1: H1) purifying the aqueous dispersion of the particles obtained according to step G1; and
(d) step K1) following step J1: K1) purifying of the particles.

### Claim 27 (depends on 1)

The method according to claim 1, wherein the Fe(III) salt is selected from the group consisting of Fe(NO3)3, FeCl3 and FePO4.

### Claim 28 (depends on 1)

The method according to claim 1, wherein in step B1) the composition is heated at a temperature of 100-150° C. for a minimum period of 30 minutes.

### Claim 29 (depends on 1)

The method according to claim 1, wherein the heating according to step C1) is carried out over a minimum period of 10 hours.