Modified alginate copolymer, alginate nanoparticle and applications thereof

Patent metadata

Field	Value
Publication number	US-2019367656-A1
Application number	US-201816479583-A
Country	US
Kind code	A1
Filing date	Jan 22, 2018
Priority date	Jan 20, 2017
Publication date	Dec 5, 2019
Grant date	—

Abstract

There is provided a modified alginate copolymer comprising an alginate backbone and having a grafted moiety attached to one of the hydroxyl groups of the alginate backbone, the grafted moiety comprising a polymer and a stabilizing group, the stabilizing group comprising at least 2 heteroatoms independently selected from the group consisting of N, S, P and Si. In a preferred embodiment, poyl(ethylene glycol)methyl ether methacrylate is grafted onto alginate via macroRAFT polymerization or ‘click’ Chemistry approach. There is provided a drug delivery method using the cation-mediated self-assembly of modified alginate copolymer as defined herein. There is provided a process to make the modified alginate copolymer as defined herein. There are further provided cosmetic applications and medical applications of the modified alginate copolymer as defined herein.

First claim

1 . A modified alginate copolymer comprising an alginate backbone and having a grafted moiety attached to one of the hydroxyl groups of the alginate backbone, the grafted moiety comprising a polymer and a stabilizing group, the stabilizing group comprising at least 2 heteroatoms independently selected from the group consisting of N, S, P and Si.

2 . The modified alginate copolymer of claim 1 , wherein the polymer is an acrylate-based polymer.

3 . The modified alginate copolymer of claim 2 , wherein the acrylate-based polymer is a methacrylate-based polymer.

4 . The modified alginate copolymer of claim 1 , wherein the polymer comprises an oligo(ethylene glycol) moiety.

5 . The modified alginate copolymer of claim 4 , wherein the oligo(ethylene glycol) moiety is attached to the oxygen atom of a carbonyl ester.

6 . The modified alginate copolymer of claim 1 , wherein the grafted moiety is attached to one of the hydroxyl groups of the alginate backbone by way of a carbonyl ester bond.

7 . The modified alginate copolymer of claim 1 , wherein the stabilizing group is a functional group selected from the group consisting of a thiocarbonate, an azide and a 5 or 6-membered heterocycle.

8 . The modified alginate copolymer of claim 7 , wherein the thiocarbonate is a trithiocarbonate.

9 . The modified alginate copolymer of claim 7 , wherein the 5 or 6-membered heterocycle is an azole or azoline.

10 . The modified alginate copolymer of claim 9 , wherein the azole is selected from the group consisting of pyrazole, triazole, imidazole, 1-pyrazoline, 2-pyrazoline, 3-pyrazoline, 1, 2, 3-thiadiazole, 1, 2, 4-thiadiazole, 1, 2, 5-thiadiazole, 1, 3, 4-thiadiazole, 1, 4, 2-dithiazole, 1, 2, 5 dithiazole, 1, 3, 4 dithiazole and 1, 2, 2, 4-dithiazole.

11 . The modified alginate copolymer of claim 1 , wherein the alginate backbone has a molecular weight between 1 and 1000 kDa.

12 . The modified alginate copolymer of claim 1 , wherein the alginate backbone has been modified to have a molecular weight between 10 and 500 kDa.

13 . A drug delivery method, the method comprising dissolving the modified alginate copolymer of claim 1 in a first solvent, and subjecting the solution to an M 2+ -containing source, subsequently collecting the solid of the ensuing reaction mixture and redispersing the obtained solid in a second solvent.

14 . The drug delivery method of claim 13 , wherein the method further comprises subjecting the solution to a bioactive agent before subjection to the M 2+ -containing source.

15 . The drug delivery method of claim 13 , wherein the M 2+ -containing source is selected from the group consisting of a Ca 2+ -containing source and a Pt 2+ -containing source.

16 . (canceled)

17 . The drug delivery method of claim 15 , wherein the M 2+ -containing source is an aqueous solution comprising CaCl 2 and/or Pt(NH 3 ) 2 Cl 2 .

18 . (canceled)

19 . A process for making a modified alginate copolymer of claim 1 comprising subjecting alginate to an acid to obtain alginic acid, subjecting alginic acid to an alkylammonium solution to obtain an aginate-alkylammonium-salt, grafting a moiety on the alginate backbone, the moiety comprising a stabilizing group, and polymerizing the grafted moiety with a polymerizable moiety, wherein one of the grafted moiety or the polymerizable moiety comprises a stabilizing group, the stabilizing group comprising at least 2 heteroatoms independently selected from the group consisting of N, S, P and Si.

20 - 26 . (canceled)

27 . An alginate nanoparticle comprising a modified alginate copolymer of claim 1 and M 2+ .

28 . (canceled)

29 . The alginate nanoparticle of claim 27 , wherein the alginate nanoparticle encapsulates the M 2+ .

30 - 35 . (canceled)

36 . A method of treating cancer comprising administering an effective amount of the alginate nanoparticle of claim 29 to a mammal, wherein the alginate nanoparticle further comprises a bioactive agent.

37 . (canceled)

Assignees

• Agency Science Tech & Res

Inventors

• Kumar Jatin

Classifications

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• C08F251/00 Primary

  Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof · CPC title

• A61Q11/00

  Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses · CPC title

• C08F299/024

  the unsaturation being in acrylic or methacrylic groups · CPC title

• C08F2438/03

  Use of a di- or tri-thiocarbonylthio compound, e.g. di- or tri-thioester, di- or tri-thiocarbamate, or a xanthate as chain transfer agent, e.g . Reversible Addition Fragmentation chain Transfer [RAFT] or Macromolecular Design via Interchange of Xanthates [MADIX] · CPC title