FUNCTIONALIZED ADHESIVE MEDICAL GEL

• US 20100215748A1
• Filed: 02/19/2010
• Published: 08/26/2010
• Est. Priority Date: 02/21/2009
• Status: Active Grant

• Current Assignee: Sofradim Production
• Original Assignee: Sofradim Production
• Inventors: Ladet, Sebastien, Gravagna, Philippe
• Granted Patent: US 8,663,689 B2
• Time in Patent Office: Days
• US Class Current: 424/487
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61L 24/0031 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 24/046 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L24/043 takes precedence
• CPC Class Codes: C08L 101/02 characterised by the presence of specified groups , e.g. terminal or pendant functional groups

Abstract

A bioadherent substrate includes a medical gel or medical gel precursor having a plurality of reactive members of a specific binding pair attached on or adapted to be attached to a surface of the medical gel, said reactive members being capable of forming covalent bonds with a plurality of complementary reactive members of the specific binding pair via a reaction selected from a Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction. A method for adhering a medical gel to biological tissue includes providing a medical gel or a medical gel precursor having a plurality of reactive members of a specific binding pair attached on or adapted to be attached to a surface of the medical gel and providing tissue with a plurality of complementary reactive members of the specific binding pair, wherein upon contact of the reactive members on the medical gel with the complimentary reactive members on the tissue, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the medical gel to the tissue.

Claims

1. A method for adhering a medical gel to biological tissue comprising:

providing a medical gel having a plurality of reactive members of a specific binding pair attached to the medical gel; and

providing tissue with a plurality of complementary reactive members of the specific binding pair, wherein upon contact of the reactive members of the medical gel with the complimentary reactive members of the tissue, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the medical gel to the tissue.

2. The method for adhering a medical gel to biological tissue according to claim 1 wherein the members of the specific binding pair bind to one another via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

3. The method for adhering a medical gel to biological tissue according to claim 2 wherein the members of the specific binding pair are alkynes and azides.

4. The method for adhering a medical gel to biological tissue according to claim 3 wherein the reactive member is an alkyne and the complementary reactive member is an azide.

5. The method for adhering a medical gel to biological tissue according to claim 3 wherein the reactive members is an azide and the complementary reactive member is an alkyne.

6. The method for adhering a medical gel to biological tissue according to claim 2 wherein the reaction is catalyzed by metal to activate an alkyne and an azide for [3+2] cycloaddition.

7. The method for adhering a medical gel to biological tissue according to claim 2 wherein the reaction involves a cyclooctyne reagent and an azide for [3+2] cycloaddition.

8. The method for adhering a medical gel to biological tissue according to claim 2 wherein the members of the specific binding pair are thiols and alkenes

9. The method for adhering a medical gel to biological tissue according to claim 2 wherein the members of the specific binding pair are dienes and alkenes.

10. The method for adhering a medical gel to biological tissue according to claim 2 wherein the tissue is provided with complementary reactive members of the specific binding pair by applying a mixture or an aerosol containing the complementary reactive members to the tissue, the complementary reactive members being conjugated to a linker adapted to link the complementary reactive members to the tissue.

11. The method for adhering a medical gel to biological tissue according to claim 10 wherein the complementary reactive members are attached to the tissue via an RGD linker.

12. The method for adhering medical gel to biological tissue according to claim 10 wherein the complementary reactive members are attached to the tissue via a ligand-receptor linkage.

13. The method for adhering medical gel to biological tissue according to claim 12 wherein the complementary reactive members are conjugated to a linker selected from the group consisting of antibody, Fab, F(ab′

)₂, Fv, single chain antibody (SCA) and single complementary-determining region (CDR).

14. The method for adhering medical gel to biological tissue according to claim 10 wherein the linker is degraded by hydrolysis or enzymatic action.

15. The method for adhering a medical gel to biological tissue according to claim 10 wherein the ligand binds to a receptor selected from the group consisting of peptides, oligosaccharides, oligonucleotides and lipids.

16. The method for adhering a medical gel to biological tissue according to claim 1 wherein the medical gel is made of a polymer selected from the group consisting of polysaccharides, mucopolysaccharides, polyaminoacids, proteins, collagen-hydroxyethyl-methacrylate (HEMA), polyphosphazines, polyphosphoesters, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyethylene oxide-co-polypropyleneoxide block copolymers, PGA-PEG-PGA block copolymers, PGA-PEG diblock copolymers, acrylates, PEG-oligoglycolylacrylates, polyacrylonitriles (PAN), carboxy alkyl celluloses, poly(α

-hydroxy) acids, polylactones, polycaprolactones, polyanhydrides, polyorthoesters, polydioxanone, styrene, acrolein and copolymers, block copolymers, homoploymers, blends and combinations thereof.

17. The method for adhering a medical gel to biological tissue according to claim 16 wherein the mucopolysachamides are selected from the group consisting of hyaluronic acid, dextran, heparin sulfate, chondroitin sulfate, heparin, agar, starch, and alginate;

the proteins are selected from the group consisting of fibronectin, gelatin, collagen, fibrin, pectins, albumin, ovalbumin, and polyamino acids;

the acrylates are selected from the group consisting of diacrylates, oligoacrylates, methacrylates, dimethacrylates and oligomethoacrylates;

the carboxy alkyl celluloses are selected from the group consisting of carboxymethyl cellulose and partially oxidized cellulose;

poly(α

-hydroxy) acids selected from the group consisting of polyglycolic acid, poly-DL-lactic, poly-L-lactic acid, and terpolymers of DL-lactide and glycolide; and

polylactones selected from the group consisting of poly(ε

-caprolactone), poly(δ

-valerolactone) and poly(γ

-butyrolactone), ε

-caprolactone copolymerized with polyesters.

18. A kit comprising a functionalized medical gel or medical gel precursor having a plurality of reactive members of a specific binding pair adapted to be presented on a surface of the gel;

a container containing a mixture which may be a solution or suspension containing complementary reactive members of the specific binding pair, the complementary reactive members having a functionality that will adhere them to biological tissue upon contact; and

at least one applicator adapted to deliver the functionalized medical gel or medical gel precursor or the mixture to biological tissue.

19. A bioadherent substrate comprising a medical gel or medical gel precursor having a plurality of reactive members of a specific binding pair adapted to be attached on a surface of the medical gel, said reactive members being capable of forming covalent bonds with a plurality of complementary reactive members of the specific binding pair via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

20. The bioadherent substrate according to claim 19 wherein the medical gel is a hydrogel.

21. The bioadherent substrate according to claim 19 wherein the members of the specific binding pair are alkynes and azides.

22. The bioadherent substrate according to claim 19 wherein the reaction is catalyzed by copper to activate an alkyne and an azide for [3+2] cycloaddition.

23. The bioadherent substrate according to claim 19 wherein the reaction involves a cyclooctyne reagent and an azide for [3+2] cycloaddition.

24. The bioadherent substrate according to claim 19 wherein the members of the specific binding pair are thiols and alkenes.

25. The bioadherent substrate according to claim 19 wherein the members of the specific binding pair are dienes and alkenes.

26. The bioadherent substrate according to claim 19 wherein the medical gel is made of a polymer selected from the group consisting of polysaccharides, mucopolysaccharides, polyaminoacids, proteins, collagen-hydroxyethyl-methacrylate (HEMA), polyphosphazines, polyphosphoesters, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyethylene oxide-co-polypropyleneoxide block copolymers, PGA-PEG-PGA block copolymers, PGA-PEG diblock copolymers, acrylates, PEG-oligoglycolylacrylates, polyacrylonitriles (PAN), carboxy alkyl celluloses, poly(α

-hydroxy) acids, polylactones, polycaprolactones, polyanhydrides, polyorthoesters, polydioxanone, styrene, acrolein and copolymers, block copolymers, homoploymers, blends and combinations thereof.

27. A method of forming a medical device having a selectively adhesive surface comprising:

providing a polymer capable of forming a hydrogel; and

functionalizing the polymer by attaching a plurality of reactive members of a specific a specific binding pair to the polymer, said reactive members being capable of forming covalent bonds with a plurality of complementary reactive members of the specific binding pair via a reaction selected from the group consisting of Huisgen cycloaddition reaction, a Diels-Alder reaction and a thiol-ene reaction.

28. The method of forming a medical device having a selectively adhesive surface according to claim 27 wherein the members of the specific binding pair are alkynes and azides.

29. The method of forming a medical device having a selectively adhesive surface according to claim 27 wherein the reaction is catalyzed by copper to activate an alkyne and an azide for [3+2] cycloaddition.

30. The method of forming a medical device having a selectively adhesive surface according to claim 27 wherein the reaction involves a cyclooctyne reagent and an azide for [3+2] cycloaddition.

31. The method of forming a medical device having a selectively adhesive surface according to claim 27 wherein the members of the specific binding pair are thiols and alkenes.

32. The method of forming a medical device having a selectively adhesive surface according to claim 27 wherein the members of the specific binding pair are dienes and alkenes.

33. The method of forming a medical device having a selectively adhesive surface according to claim 27 wherein the hydrogel is made of a polymer selected from the group consisting of polysaccharides, mucopolysaccharides, polyaminoacids, proteins, collagen-hydroxyethyl-methacrylate (HEMA), polyphosphazines, polyphosphoesters, polyethylene glycol, polyethylene oxide, polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyethylene oxide-co-polypropyleneoxide block copolymers, PGA-PEG-PGA block copolymers, PGA-PEG diblock copolymers, acrylates, PEG-oligoglycolylacrylates, polyacrylonitriles (PAN), carboxy alkyl celluloses, poly(α

-hydroxy) acids, polylactones, polycaprolactones, polyanhydrides, polyorthoesters, polydioxanone, styrene, acrolein and copolymers, block copolymers, homoploymers, blends and combinations thereof.