Manufacturing method for nanoparticle

Patent metadata

Field	Value
Publication number	US-10035887-B2
Application number	US-201514830187-A
Country	US
Kind code	B2
Filing date	Aug 19, 2015
Priority date	Aug 19, 2015
Publication date	Jul 31, 2018
Grant date	Jul 31, 2018

Abstract

A manufacturing method for nanoparticles including an amphiphilic block polymer having a uniform particle diameters has steps of forming a laminar flow of polymer solution by inducing a solution comprising an amphiphilic block polymer having a hydrophilic block and a hydrophobic block in an organic solvent into a polymer solution supply flow passage, a step of forming at least two laminar flows of a water system solution by inducing the water system solution to at least two water system solution supply passages, and a step of forming nanoparticles comprising the amphiphilic block polymer by making a confluence as if at least two laminar flows of water system solution sandwich the laminar flow of the polymer solution.

First claim

What is claimed is:

1. A method for manufacturing nanoparticles comprising an amphiphilic block polymer having a hydrophilic block and a hydrophobic block, comprising the steps of:
(a) providing a micro flow cell comprising
a polymer solution inlet;
a polymer solution supply flow passage operatively connecting to said polymer solution inlet;
at least two water system solution inlets;
at least two water system solution supply flow passages operatively connecting to each said water system solution inlet;
a confluent section, wherein said polymer solution supply flow passage is sandwiched by and is confluent with said at least two water system solution supply flow passages;
a nanoparticle forming flow passage in place in a downstream side of said confluent section; and
a nanoparticle inclusion solution outlet in a downstream end of said nanoparticle forming flow passage;

(b) introducing an amphiphilic block polymer inclusion solution into said polymer solution inlet and providing a laminar flow of said polymer solution to said confluent section through said polymer solution supply flow passage during a use;
(c) introducing a water system solution into said at least two water system solution inlets and providing at least two laminar flows of said water system solution to said confluent section through said at least two water system supply flow passages during said use;
(d) contacting said laminar flow of said polymer solution and said laminar flow of said water system solution with each other within said confluent section, forming a continuous confluent laminar flow wherein at least said two laminar flows of water system solution bound and sandwich the laminar flow of said polymer solution;
(e) thereby forming within said nanoparticle forming flow passage, nanoparticles comprising said amphiphilic block polymer; and
(f) obtaining a solution containing said formed nanoparticles from said nanoparticles inclusion solution outlet;
wherein the diameter of said laminar flow of said polymer solution in said confluent zone is about 100 μm, the flow rate of said laminar flow of said polymer solution is at least 2000 μL/min, and the nanoparticles are monodisperse with a polydispersity index of 0.14 or less.

2. The method for manufacturing, according to claim 1 , wherein:
said micro flow cell further comprises;
a substrate;
a resin film that is in-place on said substrate, wherein said polymer solution supply flow passage, said at least two water system solution supply flow passage, said confluent section, and said nanoparticle formation flow passage are formed;
a cover sheet that is in-place on said resin film, wherein said polymer solution inlet is formed at the position corresponding to the upperstream end of said polymer solution supply flow passage, said at least two water system solution inlets are formed at positions corresponding to respective upperstream ends of said two water system solution supply flow passages, and forming said nanoparticles inclusion solution outlet at a position corresponding to the downstream end of said nanoparticle formation flow passage; and
said substrate and said resin film, and said resin film and said cover sheet are respectively operatively connected in a liquid-tight state during said use.

3. The method for manufacturing, according to claim 2 , wherein:
said confluent section of said micro flow cell is formed at a location proximate a convergence of said two water system solution supply flow passages relative to said polymer solution supply flow passage;
said laminar flows of said water system solutions operative to sandwich said laminar flow of polymer solution from an opposing right side and an opposing left side relative the flow direction of said polymer solution and toward downstream side from the upperstream side at the downstream end of said polymer solution supply flow passage, whereby said polymer solution is uniformly bound by said laminar flow.

4. The method for manufacturing, according to claim 3 , wherein:
said amphiphilic block polymer further comprises:
one of a hydrophilic block having one of alkylene oxide unit and a sarcosine unit and a hydrophobic block having hydroxy acid unit.

5. The method for manufacturing, according to claim 3 , wherein:
said amphiphilic block polymer further comprises:
one of said hydrophilic block having a sarcosine unit and a hydrophobic block having lactic acid unit.

6. The method for manufacturing, according to claim 4 , wherein:
the total sarcosine units included in said hydrophilic block are in the range of 2-300.

7. The method for manufacturing, according to claim 6 , wherein:
the total lactic acid units included in said hydrophobic block are in the range of 5-400.

8. The method for manufacturing, according to claim 7 , wherein:
respective particle diameters of said formed nanoparticles is in the range of 10-200 nm.

9. The method for manufacturing, according to claim 8 , wherein:
a particle size distribution relative to the formed nanoparticles provides a single peak property.

10. The method for manufacturing, according to claim 9 , further compromising:
in said polymer solution, at least one of a pharmaceutical agent, a labeling agent obtained by inclusion with the pharmaceutical agent, and a labeling agent.

11. The method for manufacturing, according to claim 9 , further compromising:
in said water solution, at least one of a pharmaceutical agent, a labeling agent obtained by inclusion with the pharmaceutical agent, and a labeling agent.

12. The method for manufacturing, according to claim 5 , wherein:
the total sarcosine units included in said hydrophilic block are in the range of 2-300.

13. The method for manufacturing, according to claim 12 , wherein:
the total lactic acid units included in said hydrophobic block are in the range of 5-400.

14. The method for manufacturing, according to claim 13 , wherein:
respective particle diameters of said formed nanoparticles is in the range of 10-200 nm.

15. The method for manufacturing, according to claim 14 , wherein:
a particle size distribution relative to the formed nanoparticles provides a single peak property.

16. The method for manufacturing, according to claim 15 , further compromising:
in said polymer solution, at least one of a pharmaceutical agent, a labeling agent obtained by inclusion with the pharmaceutical agent, and a labeling agent.

17. The method for manufacturing, according to claim 15 , further compromising:
in said water solution, at least one of a pharmaceutical agent, a labeling agent obtained by inclusion with the pharmaceutical agent, and a labeling agent.

Assignees

• Shimadzu Corp

Inventors

• Kawabe Takashi
• OZEKI Elichi

Classifications

• B01J19/0093

  Microreactors, e.g. miniaturised or microfabricated reactors (laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027) · CPC title

• B82Y40/00

  Manufacture or treatment of nanostructures · CPC title

• B01F13/0062

  Operations & Transport · mapped topic

• C08J3/12 Primary

  Powdering or granulating · CPC title

• B01J2/06

  in a liquid medium · CPC title