Nanoparticles

Patent metadata

Field	Value
Publication number	US-11957793-B2
Application number	US-201917270160-A
Country	US
Kind code	B2
Filing date	Aug 23, 2019
Priority date	Aug 23, 2018
Publication date	Apr 16, 2024
Grant date	Apr 16, 2024

Abstract

The present invention provides a nanoparticle comprising a poly(alkyl cyanoacrylate) homopolymer, or copolymer, at least one active agent and an anionic and radical inhibitor, wherein the anionic and radical inhibitor is a compound having the following formula: wherein R1 is H; and R3, R4, R5, R6 and R7 are independently selected from the group consisting of —H, —OH, C1-C6 alkoxide, C1-C6 alkyl, halides, carboxylic acid, ketone or aldehyde; wherein the anionic and radical inhibitor is present in an amount of 0.001 to 15 wt %, as well as a process suitable for manufacture of the nanoparticle.

First claim

The invention claimed is:

1. A nanoparticle comprising a poly(alkyl cyanoacrylate) homopolymer, or copolymer, at least one active agent and an anionic and radical inhibitor, wherein
the anionic and radical inhibitor is a compound having the following formula:

wherein
R 1 is H; and
R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from the group consisting of —H, —OH, C 1 -C 6 alkoxide, C 1 -C 6 alkyl, halides, carboxylic acid, ketone and aldehyde; wherein the anionic and radical inhibitor is present in an amount of 0.001 to 15 wt %, based on the weight of the nanoparticle.

2. The nanoparticle according to claim 1 , wherein the active agent is a compound having a functional group selected from the group consisting of M-NH 3 (wherein M is a metal), R—NH 2 , R 1 R 2 —NH, R 1 R 2 R 3 N, R 1 ═NR 2 , R—OH, R—Cl, R—Br, R—I, R—SH, R 1 N═NR 2 , R—NHOH, structurally associated H 2 O, and enols.

3. The product of the process according to claim 1 .

4. A process for the preparation of nanoparticles of a poly(alkyl cyanoacrylate) homopolymer or copolymer, comprising, in a single step, the anionic polymerisation of an oil-in-water miniemulsion, wherein said miniemulsion comprises
(i) at least one alkyl cyanoacrylate monomer;
(ii) at least one surfactant;
(iii) one or more active agents;
(iv) optionally an anionic polymerisation initiator; and
(v) an anionic and radical inhibitor, wherein the anionic and radical inhibitor is a compound having the following formula:

wherein
R 1 is H; and
R 3 , R 4 , R 5 , R 6 and R 7 are independently selected from the group consisting of —H, —OH, C 1 -C 6 alkoxide, C 1 -C 6 alkyl, halides, carboxylic acid, ketone and aldehyde.

5. The process according to claim 4 , wherein the anionic and radical inhibitor is a single compound which reacts reach with any of a nucleophile and a radical.

6. The process according to claim 4 , wherein the anionic and radical inhibitor is present in an amount of 0.001 to 15 wt % of an oil phase of the miniemulsion.

7. The process according to claim 4 , wherein the anionic and radical inhibitor has a higher affinity for radicals and nucleophiles than the at least one alkyl cyanoacrylate monomer.

8. The process according to claim 4 , wherein the anionic and radical inhibitor has an octanol-water partition coefficient (log P) in the range of 1.0-3.0.

9. The process according to claim 4 , wherein the anionic and radical inhibitor is selected from the group consisting of 4-hydroxy-3,5-dimethylbenzaldehyde, 4-hydroxy-3,5-dimethoxybenzaldehyde, vanillin, salicylaldehyde and benzaldehyde.

10. The process according to claim 4 , wherein the active agent is a therapeutic agent or an imaging agent.

11. The process according to claim 4 , wherein the at least one surfactant is at least one polyalkylene glycol selected from the group consisting of polyethylene glycols (PEG), polypropylene glycols (PPG), and mixtures thereof.

12. The process according to claim 4 , wherein the at least one surfactant initiates the anionic polymerisation reaction.

13. The process according to claim 4 , wherein the at least one surfactant in step (ii) comprises at least two polyalkylene glycols selected from the group consisting of polyethylene glycols (PEG), polypropylene glycols (PPG), and mixtures thereof.

14. The process according to claim 4 , wherein the active agent comprises a functional group selected from the group consisting of M-NH 3 (wherein M is a metal), R—NH 2 , R 1 R 2 —NH, R 1 R 2 R 3 N, R 1 ═NR 2 , R—OH, R—Cl, R—Br, R—I, R—SH, R 1 N═NR 2 , R—NHOH, structurally associated H 2 O, and enols.

15. A pharmaceutical composition comprising the nanoparticle as defined in claim 1 and one or more pharmaceutically acceptable carriers, diluents or excipients.

16. A method of drug delivery or molecular imaging comprising administering the nanoparticle of claim 1 .

17. A method of agriculture, aquaculture, antibacterial applications, nutraceuticals, food/feed applications, cosmetics, self-healing, household applications, or body care comprising administering or applying the nanoparticle of claim 1 .

Assignees

• Sintef Tto As

Inventors

• Schmid Ruth
• Molesworth Peter
• Mørch Yrr
• Sulheim Einar
• Johnsen Heidi

Classifications

• A61K9/5138 Primary

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates · CPC title

• A61K9/5192

  Processes · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title