Device for formulating particles at small volumes

Patent metadata

Field	Value
Publication number	US-2016235688-A1
Application number	US-201415029993-A
Country	US
Kind code	A1
Filing date	Oct 16, 2014
Priority date	Oct 16, 2013
Publication date	Aug 18, 2016
Grant date	—

Abstract

Methods and devices for making particles at small volumes.

First claim

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1 . A method for making particles, comprising:
(a) introducing a first stream comprising a first solvent into a channel; wherein the channel has a first region adapted for flowing one or more streams introduced into the channel and a second region for mixing the contents of the one or more streams; and wherein the first solvent comprises a therapeutic material and optionally one or more particle-forming materials; (b) introducing a second stream comprising one or more particle-forming materials and optionally a therapeutic material in a second solvent into the channel to provide first and second streams and wherein the first and second solvents are not the same; (c) flowing the one or more first streams and the one or more second streams from the first region of the channel into the second region of the channel such that the one or more first streams and the one or more second streams arrive at the second region for mixing at substantially the same time; and (d) mixing the contents of the one or more first streams and the one or more second streams in the second region of the channel to provide a third stream comprising particles.

2 . The method of claim 1 , wherein mixing the contents of the one or more first streams and the one or more second streams comprises varying the concentration or relative mixing rates of the one or more first streams and the one or more second streams.

3 . The method of claim 2 , wherein the relative mixing rates are achieved by either different pressure drops across the flow channels, different pressures applied to the flows, or combination therein, applied to the first and second streams;

4 . The method of claims 1 - 3 further comprising diluting the third stream with an aqueous buffer.

5 . The method of any one of claims 1 - 4 , wherein after or during manufacture of particles, flowing into the one or more first streams and the one or more second streams from the first region of the channel into the second region of the channel a fluid or gas to expel the first stream and second streams.

6 . The method of claim 5 , wherein the gas used to expel the first and second streams is the resultant from the pressure source applied to drive fluid flow of the first and second streams.

7 . The methods of any one of claims 1 - 6 , wherein backpressure is applied to ensure the flows of the one or more first streams and the one or more second streams from the first region of the channel into the second region is limited until an initial desired input pressure is achieved.

8 . The method of any one of claims 1 - 6 , wherein a stopper is applied to the outlet port to prevent the flowing of material until an initial input pressure is achieved.

9 . The method of claim 8 , wherein the stopper is achieved through a fluid blocking the outlet port.

10 . The method of claim 9 , wherein the fluid is a dilution buffer.

11 . The method of claim 8 , wherein the outlet port is controlled with a valve.

12 . The methods of any one of claims 1 - 11 , wherein the particles are lipid particles with polynucleic acids encapsulated.

13 . The method of any one of claims 1 - 11 , wherein the first solvent is an aqueous buffer.

14 . The method of any one of claims 1 - 11 , wherein the second solvent is an aqueous alcohol.

15 . The method of claim 12 , wherein the polynucleic acid is a DNA, a RNA, a locked nucleic acid, a nucleic acid analog, or a plasmid capable of expressing a DNA or an RNA, or a combination of one or more polynucleic acids

16 . The method of claim 12 , wherein the polynucleic acid is an oligonucleotide.

17 . The method of claim 12 , wherein the polynucleic acid is ssDNA or dsDNA.

18 . The method of claim 12 , wherein the polynucleic acid is siRNA or microRNA.

19 . The method of claim 12 , wherein the polynucleic acid is an antisense oligonucleotide.

20 . The method of claim 12 , wherein the polynucleic acid is an mRNA

21 . The method of any one of claims 1 - 20 , wherein the particle-forming materials comprise an amino lipid.

22 . The method of any one of claims 1 - 21 , wherein the second stream further comprises a polyethylene glycol-lipid.

23 . The method of any one of claims 1 - 22 , wherein the second stream further comprises a neutral lipid.

24 . The method of any one of claims 1 - 23 , wherein the second stream further comprises a surfactant.

25 . The method of any one of claims 1 - 24 , wherein mixing the contents of the first and second streams comprises chaotic advection.

26 . The method of any one of claims 1 - 24 , wherein the second region of the channel comprises bas-relief structures.

27 . The method of any one of claims 1 - 26 , wherein the second region of the channel has a principal flow direction and one or more surfaces having at least one groove or protrusion defined therein, the groove or protrusion having an orientation that forms an angle with the principal direction.

28 . The method of any one of claims 1 - 26 , wherein mixing the contents of the first and second streams comprises mixing with a micromixer.

29 . The method of claim 12 , wherein the polynucleic acid encapsulation efficiency is from about 60 to about 100%.

30 . The method of claim 12 , wherein the polynucleic acid encapsulation efficiency is from about 80 to about 100%.

31 . The method of claim 12 , wherein recovery of the lipid particles with polynucleic acids encapsulated is from 80% to 100%

32 . The method of claim 12 , wherein recovery of the lipid particles with polynucleic acids encapsulated is from 90% to 100%

33 . The method of claim 12 , wherein recovery of the lipid particles with polynucleic acids encapsulated is from 95% to 100%

34 . A particle made by the method of any one of claims 1 - 33 .

35 . A method for making particles, comprising:
(a) introducing a stream comprising a first solvent into a channel; wherein the channel has a first region adapted for flowing one or more streams introduced into the channel; and (b) conducting the first stream through the channel and into a reservoir comprising a second solvent, wherein conducting the first stream into the reservoir comprises mixing the contents of the first stream with the contents of the reservoir to provide particles.

36 . A particle made by the method of claim 35 .

37 . A device, comprising:
(a) a first well for receiving a first solution comprising a first solvent; (b) a first channel in fluid communication with the first well; (c) a second well for receiving a second solution comprising a second solvent; (d) a second channel in fluid communication with the second well; (e) a third channel for receiving first and second streams flowed from the first and second wells through the first and second channels, respectively, wherein the third channel has a first region adapted for flowing the first and second streams introduced into the channel and a second region adapted for mixing the contents of the first and second streams to provide a third stream comprising particles; and (f) a third well for receiving the third strea

Assignees

• Walsh Colin
• Univ British Columbia

Inventors

• Walsh Colin
• Wild Andre
• Taylor Robert James
• Leaver Timothy
• Ou Kevin
• Ramsay Euan
• Ansari Aysha

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• A61K9/5192 Primary

  Processes · CPC title

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• B01J2/06

  in a liquid medium · CPC title