# US 8,540,939 B2 · Instrument and process for nanoparticles production in continuous flow mode

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- Number: US 8,540,939 B2
- Document ID: US8540939B2
- Status: Granted
- Kind: B2
- Application number: 12/990,195
- Filed: 2009-04-28
- Published: 2011-05-05
- Granted: 2013-09-24
- Earliest claimed: 2008-04-28
- Assignees: Darholding Vagyonkezelo Korlatolt Felelossegu Tarsasag
- Applicants: Krisztián Niesz; Atilla Wootsch; Maxime Groualle; Zsolt Ötvös; Ferenc Darvas
- Inventors: Krisztián Niesz; Atilla Wootsch; Maxime Groualle; Zsolt Ötvös; Ferenc Darvas
- Web page: https://patentgrep.com/patent/US8540939B2

## CPC

- B01J 13/0004: {Preparation of sols (by physical processes B01J13/0086, aerosols B01J13/0095)}
- A61K 9/146: {with organic macromolecular compounds}
- A61K 9/5138: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61K 9/5161: {Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin}
- A61P 3/06: Antihyperlipidemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 15/10: for impotence
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- B01J 13/02: Making microcapsules or microballoons {(for medical preparations A61K9/50)}
- B01J: CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- 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

## Abstract

A continuous flow system for the synthesis of nanoparticles includes a feeding unit connected to the first reactor a flow path, at least one first reactor unit possessing a heatable reactor-zone, a second reactor unit which follows the first reactor in the same cascade; a mixing unit and a second feeding unit between the reactor units, and feeding pumps connected to a raw material source and/or a control unit which is capable of controlling at least one pressure controller and/or controlling the temperature of at least one heatable reactor-zone; each heatable reactor-zone is followed by a cooling unit in the cascade. In addition, a process for the synthesis of nanoparticles, preferably metal-containing nanoparticles, and nanoparticles of biologically active organic molecules wherein the process is accomplished using the system.

## Claims

### Claim 1

A continuous flow device (50) for executing a process of preparation of nanostructures, the device (50) comprising:
a first feeding unit (1a) with a first feed pump (9) connected to a first raw material source (7);
a second feeding unit (1b) with a second feed pump (10) connected to a second raw material source (8);
a first reactor unit (2) with a first reactor-zone unit (13) configured to receive material from the first feeding unit to heat to a given first temperature value and to feed into a first cooling unit (14) comprising a first countercurrent heat-exchanger configured to provide an enhanced rate of heat exchange to decrease particle size of nanostructures being prepared by the device;
a mixing unit (5) configured to receive an output from the first cooling unit (14) and second raw material from the second feeding unit (1b);
a second reactor unit (3) with a second reactor-zone unit (15) configured to receive output from the mixing unit (5) and to be heated to a given second temperature value to feed into a second cooling unit (16) comprising a second countercurrent heat-exchanger configured to provide an enhanced rate of heat exchange to decrease particle size of nanostructures being prepared by the device;
at least one pressure controller (18) arranged in a flow path defined by the first reactor unit (2) and the second reactor unit (3) and configured to set a pressure value in the flow path;
a control unit (22) configured to control at least one of the pressure value set by the pressure controller (18), the given first temperature value, and the given second temperature value;
wherein the respective cooling units (14, 16) are configured to terminate the process of preparation of nanostructures.

### Claim 2 (depends on 1)

The device according to claim 1 further comprising a final product analyzer unit (4) comprising a dynamic light scattering analyzer operatively connected to the first cooling unit (14) and the second cooling unit (16) to continuously monitor and determine particle size and particle size distribution of the nanostructures being prepared and to adjust the first cooling unit (14) and the second cooling unit (16) in response to determined properties of the nanostructures, the analyzer unit (4) being connected to the flow path after the second reactor unit (3).

### Claim 3 (depends on 1)

The device according to claim 1, wherein the pressure controller (18) is inserted into the flow path between the second reactor unit (3) and the analyzer unit (4) to maintain a constant pressure value along the flow path.

### Claim 4 (depends on 1)

The device according to claim 1, wherein the device (50) is configured to output nanostructures comprising nanoparticles with at least one constituent.

### Claim 5 (depends on 1)

The device according to claim 1, wherein the device (50) is configured to output nanostructures comprising nanoparticles with at least one constituent comprises one of a metal or biologically active organic molecules.

### Claim 6 (depends on 1)

The device according to claim 1, wherein the device (50) is configured to output nanostructures comprising core-shell type nanoparticles.

### Claim 7 (depends on 1)

The device according to claim 1, wherein the device (50) is configured to output nanostructures chosen from the group of consisting of: nanoemulsions and colloidal solution with at least one constituent comprising a metal or biologically active organic molecules.

### Claim 8 (depends on 7)

The device according to claim 7, wherein biologically active organic molecules comprise active pharmaceutical ingredients.

### Claim 9

A method of preparing nanostructures, the method comprising:
feeding a first raw material from a first raw material source (7) to a first reactor unit (2);
a first reactor-zone (13) of the first reactor unit (2) heating the first raw material to a given first temperature value;
feeding an output of the first reactor zone (2) to a first cooling unit (14) comprising a first countercurrent heat-exchanger to provide an enhanced rate of heat exchange to decrease particle size of nanostructures being prepared;
mixing output from the first cooling unit (14) with second raw material from a second feeding unit (1b) using a mixing unit (5);
feeding output from the mixing unit (5) to a second reactor unit (3);
a second reactor-zone (15) of the second reactor unit (3) heating the output from the mixing unit (5) to a given second temperature value;
feeding an output of the second reactor zone (3) to a second cooling unit (14) comprising a second countercurrent heat-exchanger to provide an enhanced rate of heat exchange to decrease particle size of nanostructures being prepared;
controlling pressure in the first reactor unit (2) and the second reactor unit (3) to a given pressure value;
controlling temperature in the first reactor zone (13) and in the second reactor zone (15).

### Claim 10 (depends on 9)

The method according to claim 9, further comprising:
analyzing an output of the second reactor unit (3) with a dynamic light scattering analyzer to continuously monitor and determine particle size and particle size distribution of the output of the second reactor unit (3);
adjusting the first cooling unit (14) and the second cooling unit (16) in response to determined properties of output of the second reactor unit (3).

### Claim 11 (depends on 9)

The method according to claim 9, further comprising outputting from the second cooling unit (14) core-shell type nanoparticles.

### Claim 12 (depends on 9)

The method according to claim 9, further comprising outputting from the second cooling unit (14) nanoparticles of biologically active organic molecules.

### Claim 13 (depends on 12)

The method according to claim 12, wherein outputting from the second cooling unit (14) nanoparticles of biologically active organic molecules comprises outputting nanoparticles of active pharmaceutical ingredients.

### Claim 14 (depends on 9)

The method according to claim 9, further comprising outputting from the second cooling unit (14) nanostructures chosen from the group consisting of: nanoemulsions and colloidal solution with at least one constituent, preferably a metal or biologically active organic molecules.