Disintegratable porous organometaloxyde material

Patent metadata

Field	Value
Publication number	US-2016333145-A1
Application number	US-201515111506-A
Country	US
Kind code	A1
Filing date	Jan 14, 2015
Priority date	Jan 14, 2014
Publication date	Nov 17, 2016
Grant date	—

Abstract

The present invention relates to disintegratable mesoporous silica materials, a method for producing the same, and uses thereof.

First claim

1 . Disintegratable porous organometaloxide material comprising a porous three-dimensional framework of metal-oxygen bonds, wherein at least a subset of metal atoms in the material's framework are connected to at least another metal atom in the framework through a linker having one of the following structures:
*—R 1 -L-R 2 —*,

wherein:
each occurrence of * denotes a point of attachment to a metal atom in the material's framework;
A represents a monomer of a responsively cleavable fragment of biological/biodegradable polymer;
m is an integer from 2 to 10000 and m represents the number of monomers in the fragment of biological/biodegradable polymer;
L represents a responsively cleavable covalent bond, and
R 1 and R 2 independently represent an optionally substituted C1-20alkylenyl moiety, an optionally substituted C1-20heteroalkylenyl moiety, an optionally substituted ethylenyl moiety, —C≡C— or an optionally substituted phenyl moiety, wherein the C1-20alkylenyl, C1-20heteroalkylenyl or ethylenyl moiety may bear one or more substituents selected from halogen or —OR where R may represent H or C1-6alkyl, and the phenyl moiety may bear one or more substituents independently selected from halogen, C1-6alkyl, —NO 2 , —CN, isocyano, —OR p , —N(R p ) 2 wherein each occurrence of R p independently represents H or C1-6alkyl;
wherein, when the linker has the structure *—R 1 -L-R 2 —*, the subset of metal atoms in the material's framework that are connected to the linker *—R 1 -L-R 2 -*, represent at least 30% of the metal atoms present in the porous organometaloxide material.

2 . The material of claim 1 , wherein the three-dimensional framework of metal-oxygen bonds is mesoporous, microporous, macroporous or mixed mesoporous-macroporous.

3 . The material of claim 1 or 2 , wherein the linker has the structure *—R 1 -L-R 2 —*, and L represents a responsively cleavable covalent bond selected from:

4 . The material of claim 1 or 2 , wherein the linker represents a responsively cleavable fragment of biological/biodegradable polymer selected from carbohydrates, peptides and synthetic biodegradable polyethyleneglycol or polylactide polymers, and the linker has the structure

wherein A, m, R and R are as defined in claim 1 .

5 . The material of any one of claims 1 to 4 , wherein the metal is selected from Si, Ti or Zr, or any combination of at least two of these metals.

6 . The material of any one of claims 1 to 5 , wherein the material contains 90.0-100% Si, 90.0-100% Ti or 90.0-100% Zr as metal, wherein the % are based on the number of available metal sites in the framework.

7 . The material of any one of claims 1 to 5 , wherein the material is a Si—Ti mixed-metal organometaloxide material containing 0.1-50.0% Si and 0.1-50.0% Ti, the % sum of Si and Ti adding to 100% the number of available metal sites in the framework.

8 . The material of any one of claims 1 to 5 , wherein in the linker represents *—R 1 -L-R 2 —*, R 1 and R 2 are identical, and each represent —CH 2 —, —(CH 2 ) 2 —, —(CH 2 ) 3 —, —(CH 2 ) 4 —, or phenyl.

9 . The material of any one of claims 1 to 8 , said material comprising in its pores or at its surface at least one marker and/or cosmetically or pharmaceutically active principle.

10 . The material of claim 9 , wherein the marker is selected from a contrast agent, a tracer, a radioactive marker, a fluorescent marker, a phosphorescent marker, a magnetic resonance imaging agent or a positron emission tomography agent.

11 . The material of any one of claims 1 to 10 , wherein the material is in the form of a monolith, a thin or thick film, a powder, nanoparticles, or spherical, cubic, cylindrical or disc-like particles.

12 . A method for preparing a material of any one of claims 1 to 11 , comprising steps of:
a) Producing a supramolecular template by mixing a suitable surfactant and an aqueous solvent;
b) Adding a mixture of a precursor M(X A ) 4 and a selected precursor having the structure:
(X) 3 M 1 -R 1 -L-R 2 -M 2 (X) 3 ;

in an aqueous solvent under alkaline conditions; thereby coating the supramolecular template with an organometaloxide sol-gel mixture obtained by hydrolysis-condensation of metal alkoxide; and
c) Removing the supramolecular template; thereby producing a porous organometaloxide nanoparticles comprising a porous three-dimensional framework of metal-oxygen bonds, wherein at least a subset of metal atoms in the material's framework are connected to at least another metal atom in the framework through a linker having one of the following structures:
*—R 1 -L-R 2 —*,

wherein:
each occurrence of * denotes a point of attachment to a metal atom in the material's framework;

A represents a monomer of a responsively cleavable fragment of biological/biodegradable polymer;
m is an integer from 2 to 10000 and m represents the number of monomers in the fragment of biological/biodegradable polymer;
M and each occurrence of M 1 and M 2 independently represents a metal selected from Si, Ti and Zr;
each occurrence of X and X A independently represents a hydrolysable or nonhydrolyzable group, provided that on each occurrence of M 1 and M 2 , at least one occurrence of X represents a hydrolysable group and at least two occurrences of X A in the precursor M(X A ) 4 independently represent a hydrolysable group; wherein (i) when X or X A represents a nonhydrolyzable group, it may be selected from an optionally substituted C1-20alkyl, C2-20alkenyl or C2-20alkynyl moiety, an optionally substituted C1-20heteroalkyl, C2-20heteroalkynyl or C2-20heteroalkynyl moiety, or an optionally substituted phenyl moiety, wherein the substituents on the phenyl, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl and heteroalkynyl moieties may be independently selected from halogen, —NO 2 , —CN, isocyano, C1-6alkoxy, an oxirane/epoxyde moiety, —N(R) 2 wherein each occurrence of R is independently selected from H or C1-6alkyl; and (ii) when X or X A represents a hydrolysable group, it may be selected from a C1-6alkoxy, C1-6acyloxy, halogen or amino moiety;
L represents a responsively cleavable covalent bond; and
R 1 and R 2 independently represent an optionally substituted C1-20alkylenyl moiety, an optionally substituted C1-20heteroalkylenyl moiety, an optionally substituted ethylenyl moiety, —C≡C— or an optionally substituted phenyl moiety, wherein the C1-20alkylenyl, C1-20heteroalkylenyl or ethylenyl moiety may bear one or more substituents selected from halogen or —OR where R may represent H or C1-6alkyl, and the phenyl moiety may bear one or more substituents independently selected from halogen, C1-6alkyl, —NO 2 , —CN, isocyano, —OR p , —N(R p ) 2 wherein each occurrence of R p independently represents H or C1-6alkyl.

13 . The method of claim 12 , wherein the ratio of equivalents (X) 3 M1-R 1 -L-R 2 -M 2 (X) 3 /M(X A ) 4 is one listed in the table below:

Assignees

• Univ Strasbourg
• Centre Nat De La Rech Scient - Cnrs

Inventors

• De Cola Luisa
• Maggini Laura
• Prasetyanto Eko Adi

Classifications

• C08G83/008

  Supramolecular polymers · CPC title

• C08L101/16

  the macromolecular compounds being biodegradable · CPC title

• A61K31/4188

  condensed with other heterocyclic ring systems, e.g. biotin, sorbinil · CPC title

• A61K9/5192

  Processes · CPC title

• A61K9/5115

  Inorganic compounds · CPC title