Silylated biomolecules

Patent metadata

Field	Value
Publication number	US-9285360-B2
Application number	US-201113574970-A
Country	US
Kind code	B2
Filing date	Jan 25, 2011
Priority date	Jan 25, 2010
Publication date	Mar 15, 2016
Grant date	Mar 15, 2016

Abstract

The invention concerns: —a silylated biomolecule having the following formula (I): —the process for the preparation of a silylated biomolecule of formula (I), —the use of a silylated biomolecule of formula (I) to functionalize the surface of a support, —a process for the preparation of a hydrogel by use of a silylated biomolecule of formula (I), the hydrogel obtainable by said process, —said hydrogel as a biological tissue substitute, —a composition comprising said hydrogel in a pharmaceutically acceptable vehicle, —said composition for the release of active principle.

First claim

The invention claimed is:

1. A hydrogel prepared by a process comprising the steps of:
a) contacting a silylated biomolecule with a base or an acid, in an aqueous medium, wherein the silylated biomolecule has the following formula (I):

wherein:
A is a biomolecule selected from the group consisting of a hyaluronic acid, pectin, collagen, gelatin, RGDS (SEQ ID NO:1) and chitosan,
m is an integer ranging from 1 to 6,
p and q are independently 0 or 1,
X is a group chosen from —NHCONH—, —OCONH— and —CONH—, and
R 1 , R 2 and R 3 each independently represent a C 1 -C 6 alkyl group; and
b) adjusting the pH of the aqueous medium of comprising the silylated biomolecule of step a) to a pH of between 3.5 and 12.4;
whereby said silylated biomolecule auto-condensates via formation of —Si—O—Si—covalent bonds.

2. The hydrogel of claim 1 , wherein said process further comprises the step of recovering the hydrogel.

3. The hydrogel of claim 1 wherein in step a), said silylated biomolecule and said base or said acid are further contacted with a second silylated biomolecule of formula (IV):

wherein:
M is a biomolecule different from A,
Y is a linker group between the biomolecule and the silane, and
R 4 , R 5 and R 6 each independently represent a C 1 -C 6 alkyl group.

4. The hydrogel of claim 3 , wherein M is a polysaccharide.

5. The hydrogel of claim 4 , wherein said polysaccharide is cellulose, hydroxyethylcellulose or hydroxypropylmethylcellulose.

6. The hydrogel of claim 5 , wherein said polysaccharide is hydroxypropylmethylcellulose.

7. The hydrogel of claim 3 , wherein M is selected from the group consisting of a peptide, an oligopeptide, a protein, a deoxyribonucleic acid, a ribonucleic acid, pectin, chitosan, hyaluronic acid and a glycolipid, wherein M is different from A.

8. The hydrogel of claim 3 , wherein A is pectin and M is hyaluronic acid.

9. A composition comprising the hydrogel of claim 1 , and one or more cells.

10. A biological tissue substitute comprising a hydrogel prepared by a process comprising the steps of:
a) contacting a silylated biomolecule having the following formula (I):

wherein:
A is a biomolecule selected from the group consisting of a hyaluronic acid, pectin, collagen, gelatin, RGDS (SEQ ID NO:1) and chitosan,
m is an integer ranging from 1 to 6,
p and q are independently 0 or 1,
X is a group chosen from —NHCONH—, —OCONH— and —CONH—, and
R 1 , R 2 and R 3 each independently represent a C 1 -C 6 alkyl group; with a base or an acid in an aqueous medium; and
b) adjusting the pH of the aqueous medium of step a) to a pH of between 3.5 and 12.4.

11. The biological tissue substitute of claim 10 , wherein said biological tissue substitute further comprises one or more cells.

12. The biological tissue substitute of claim 11 , wherein said cells require adhesion for growth.

13. The biological tissue substitute of claim 10 , wherein said biological tissue substitute is a cartilage-like tissue substitute, a bone substitute, a heart tissue substitute or a skin substitute.

14. A composition comprising a biological tissue substitute according to claim 10 in combination with a pharmaceutically acceptable vehicle.

15. A process for the preparation of an hydrogel comprising the steps of:
a) contacting a silylated biomolecule with a base or an acid, in an aqueous medium, wherein the silyated biomolecule has the following formula (I):

wherein:
A is a biomolecule selected from the group consisting of hyaluronic acid, pectin, collagen, gelatin, RGDS (SEQ ID NO:1) and chitosan,
m is an integer ranging from 1 to 6,
p and q are independently 0 or 1,
X is a group chosen from —NHCONH—, —OCONH— and —CONH—, and
R 1 , R 2 and R 3 each independently represent a C 1 -C 6 alkyl group; and
b) adjusting the pH of the aqueous medium comprising the silylated biomolecule of step a) to a pH of between 3.5 and 12.4;
whereby said silylated biomolecule auto-condensates via formation of —Si—O—Si—covalent bonds.

16. The process according to claim 15 , wherein in step a), the silylated biomolecule and the base or the acid are further contacted with a second silylated biomolecule of formula (IV):

wherein:
M is a biomolecule different from A,
Y is a linker group between the biomolecule and the silane, and
R 4 , R 5 and R 6 each independently represent a C 1 -C 6 alkyl group.

17. Process according to claim 16 , wherein M is a polysaccharide.

18. Process according to claim 17 , wherein the polysaccharide is cellulose, hydroxyethylcellulose or hydroxypropylmethylcellulose.

19. The process according to claim 16 , wherein M is selected from the group consisting of a peptide, an oligopeptide, a protein, a deoxyribonucleic acid, a ribonucleic acid, pectin, chitosan, hyaluronic acid and a glycolipid, wherein M is different from A.

20. The process of claim 15 , further comprising the step of recovering the hydrogel.

Assignees

• Weiss Pierre
• Guicheux Jerome
• Rethore Gildas
• Rederstorff Emile
• Laib Samia
• Inst Nat Sante Rech Med
• Univ Nantes
• Chu Nantes
• Ifremer

Inventors

• Weiss Pierre
• Guicheux Jerome
• Rethore Gildas
• Rederstorff Emile
• Laib Samia

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61K47/36

  Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin · CPC title

• C08B15/05

  Derivatives containing elements other than carbon, hydrogen, oxygen, halogens or sulfur (esters or phosphorous acids C08B5/00) · CPC title

• C08G2210/00

  Compositions for preparing hydrogels · CPC title

• C08L89/06

  derived from leather or skin {, e.g. gelatin} · CPC title