SURGICAL ADHESIVES

Abstract

A composition for the adhesion of biological tissues to one another, for the adhesion of a material to a biological tissue, for the adhesion of an adhesive or of a substance to the surface of a biological tissue, for blocking an orifice in a biological tissue, for reinforcing a biological tissue and/or for fixing and stabilising a biological tissue, characterized in that it comprises a monomer that is polymerisable under the effect of ultraviolet (UV) or near visible radiation and in that the viscosity of said composition is less than 40 mPa.Math.s at 20 C.

Claims

1. A composition, intended to be used in a method for adhesion of biological tissues to one another, for adhesion of a material to a biological tissue, for adhesion of an adhesive or of a substance to a surface of the biological tissue, for blocking an orifice in the biological tissue, for reinforcing the biological tissue and/or for fixing and stabilizing the biological tissue, comprising: a monomer polymerizable under the effect of ultra-violet (UV) or near visible radiation, wherein a viscosity of the composition is less than 40 mPa.Math.s at 20 C., and wherein the composition is not a hydrogel.

2. The composition according to claim 1, wherein said UV radiation has a wavelength of between 150 nm and 280 nm.

3. The composition according to claim 1, wherein said UV radiation has a wavelength of between 200 nm and 400 nm.

4. The composition according to claim 1, wherein said near visible radiation has a wavelength of between 400 nm and 500 nm.

5. The composition according to claim 1, wherein the polymerization of the monomer is only initiated by irradiation by the UV radiation.

6. The composition according to claim 1, wherein the composition does not comprise polymerizable monomers of which polymerization can be initiated by contact with water molecules.

7. The composition according to claim 1, wherein the composition does not comprise polymerizable monomers of the cyanoacrylate family.

8. The composition according to claim 1, wherein the viscosity of the composition is less than 35 mPa.Math.s at 20 C.

9. The composition according to claim 1, wherein the viscosity of the composition is less than 30 mPa.Math.s at 20 C.

10. The composition according to claim 1, wherein said monomer is an acrylate monomer or a methacrylate monomer or an acrylate oligomer or a methacrylate oligomer.

11. The composition according to claim 1, wherein said monomer comprises a polar function.

12. The composition according to claim 11, wherein said polar function is chosen in the group comprising hydroxyl, amide, carboxyl, amino, carbonate, carbamate, sulfonamide, sulfonic, phosphonic, methoxyethyl, methoxyethoxyethyl, hydroxyethyl and hydroxyethoxyethyl functions.

13. The composition according to claim 11, wherein said monomer is chosen in the group comprising the mono-, di-, tri-, tetra- and penta-acrylate or methacrylate, and their mixtures.

14. The composition according to claim 10, wherein said acrylate monomer is chosen in the group comprising acrylic acid, methyl methacrylate; dimethylaminoethyl methacrylate; ethyl acrylate; cyclohexyl methacrylate; 2-hydroxyethyl methacrylate; 3-hydroxypropyl acrylate; alpha-bromoethyl acrylate; alpha-chloroethyl acrylate; chloromethyl methacrylate; 2-bromoethyl methacrylate; 2-naphtyl methacrylate; paratolyl acrylate; parachlorophenyl methacrylate; metabromophenyl acrylate; 2,4,6-tribromophenyl acrylate; paracholorobenzyl methacrylate; metamethoxybenzyl methacrylate; paraethylbenzyl acrylate; 1,6-hexanediol dimethacrylate; neopentylglycol diacrylate; thiodiethylene-glycol dimethacrylate; bisphenol A ethoxyl diacrylate; bisphenol A ethoxyl dimethacrylate; pentaerythritol triacrylate; glyceryl triacrylate; dipentaerythritol pentaacrylate; trimethylolpropane triacrylate; tris isocyanurate trimethacrylate (2-hydroxyethyl); trimethylolpropane polyoxyethylene triacrylate; a urethane acrylate; a urethane methacrylate; bis sulfur (4-methacryloylthiophenyl); tert-butyl acrylate; an ethyleneglycol or a polyethyleneglycol chosen in the group composed of acrylate, methacrylate; diacrylate, dimethacrylate and their mixtures.

15. The composition according to claim 10, wherein said acrylate monomer is chosen in the group comprising hydroxy (ethyl) methacrylate, acrylic acid, hydroxy (propyl) methacrylate, tert-butyl acrylate, dimethylaminoethyl methacrylate and their mixtures.

16. The composition according to claim 1, wherein said monomer has a molar mass of between 50 and 400g.Math.mol.sup.1.

17. The composition according to claim 1, wherein the composition has no solvent.

18. The composition according to claim 1, wherein said monomer has a concentration of between 50 and 100% in mass in relation to a total mass of the composition.

19. The composition according to claim 1, wherein said composition further comprises a cross-linking agent chosen in the group comprising multifunctional acrylates comprising in particular 1,6-hexanediol dimethylacrylate (HDDMA), ethylene glycol dimethylacrylate (EGDMA), Triethylene glycol dimethacrylate (TEGDMA), butanediol diacrylate (BDDA), trimethylolpropane triacrylate, 1,2-ethylene glycol diacrylate, poly (ethylene glycol) diacrylate (PEGDA), pentaerythritol tetracrylate and mixtures of these.

20. The composition according to claim 1, wherein said cross-linking agent is present at a concentration of between 1% and 35% in mass.

21. The composition according to claim 1, further comprising a photoinitiator.

22. The composition according to claim 21, wherein said photoinitiator is chosen in the group comprising 2,2-dimethoxyphenyl-2-acetophenone (DMPA), camphorquinone TPO-L, EDB (thyldimthylaminobenzoate) and 4,4-bis (diethylamino) benzophenone.

23. The composition according to claim 21, wherein said photoinitiator is at a concentration of between 0.2% and 2%.

24. A non-invasive method for adhesion of the biological tissues to one another, for adhesion of the material to the biological tissue, for adhesion of the adhesive or the substance to the surface of the biological tissue, for blocking the orifice in the biological tissue, for reinforcing the biological tissue and/or for fixing and stabilizing the biological tissue, comprising: (i) coating the tissue to treat with the composition according to claim 1, (ii) letting the composition penetrate into said biological tissue, and (iii) inducing, by the UV or near visible radiation, polymerization of said composition.

25. The method according to 24, further comprising: (iv) bringing a synthetic tissue into apposition to the surface of said biological tissue.

26. The method according to claim 24, wherein said UV radiation has a wavelength of between 150 nm and 280 nm.

27. The method according to claim 24, wherein said UV radiation has a power of between 100 W and 200 W.

28. The method according to claim 24, wherein said near visible radiation has a wavelength of between 400 nm and 500 nm.

29. A kit of parts comprising the composition according to claim 1 and a UV or near visible radiation source.

30. A composition, intended to be used in a method for adhesion of biological tissues to one another, for adhesion of a material to a biological tissue, for adhesion of an adhesive or of a substance to a surface of a biological tissue, for blocking an orifice in a biological tissue, for reinforcing a biological tissue and/or for fixing and stabilizing a biological tissue, comprising: a photoinitiator, wherein the photoinitiator is chosen in the group comprising 2,2-dimethoxyphenyl-2-acetophenone (DMPA), camphorquinone and 4,4-bis(diethylamino)benzophenone; a monomer polymerizable under the effect of ultra-violet (UV) or near visible radiation, wherein a viscosity of the composition is less than 40 mPa.Math.s at 20 C., and wherein the composition is not a hydrogel.

Description

DESCRIPTION OF EMBODIMENTS

Equipment and Methods

Peeling Test

[0063] In a first set of experiments, Acrylic acid, (hydroxethyl) methacrylate/acrylic acid, (hydroxypropyl) methacrylate/acrylic acid, acrylic acid/tert-butyl acrylate/cross-linking agent, methacrylate/acrylic acid/(hydroxyethyl) methacrylate/cross-linking agent solutions, or acrylic acid/dimethylaminoethyl methacrylate/cross-linking agent solutions of variable viscosity and concentrations have been deposited in samples of bovine pericardium. This step is carried out at 20 C. Said pericardium samples have been subjected to 150 W UV radiation, for a duration of 5 minutes, in order to trigger the polymerisation of the monomers. The radiation source has been positioned 10 cm away from the pericardium.

[0064] In a second set of experiments 10-Methacryloyloxydecyl dihydrogen phosphate/tert-butyl acrylate/cross-linking agent solutions of variable viscosity and concentrations have been deposited in samples of bovine pericardium. This step is carried out at 20 C. Said pericardium samples have been subjected to 17 mW/cm.sup.2 UV radiation, for a duration of 60 s, in order to trigger the polymerisation of the monomers.

[0065] Said pericardium samples have then been covered with a strip of glassfibre, the latter has then received a monomer solution identical to that used in the preceding step.

[0066] The pericardium samples have been subjected to UV radiation under the identical conditions as those in the preceding step.

[0067] A peeling test has then been carried out by traction at 180 on the glassfibre strip in a furnace regulated at 37 C. The rest time for the strip installed between the jaws of the traction machine is one minute, the temperature within the sample is, at the time of starting the test, 30 C., +or 4 C.

Observation at the Environment-Scanning Electronic Microscope

[0068] An acrylic acid solution has been deposited on the pericardium samples. Said pericardium samples have been subjected to UV radiation of 150 W, for 5 minutes, in order to trigger the polymerisation of the monomers. The radiation source has been positioned 10 cm away from the pericardium.

[0069] The pericardium samples have then been transversally cut and observed by scanning electronic microscopy.

Results

Peeling Test

[0070] The results obtained are presented in the table below.

[0071] In all the tests carried out, it has been observed, whatever the adhesive used, a rate of around 70% rupture in the tissue or the glassfibre strip and 30% in the adhesive. When the rupture occurs in the adhesive, the force necessary to destroy the assembly is equal to the force obtained for a rupture in the glassfibre.

[0072] It has been observed that the resistance to rupture (that is, the resistance to the bonding), is optimal for a viscosity below 40 mPa.Math.s.

TABLE-US-00001 TABLE 1 Composition used (all compositions comprise Viscosity Resistance to rupture F/b 0.25% in DMPA mass) [mPa .Math. s] [N/m] in the pericardium 100% acrylic acid 1 300 25% HEMA 75% AA 3 300 50% HEMA 50% AA 4 250 75% HEMA 25% AA 6 200 25% HPMA 75% AA 3 400 50% HPMA 50% AA 4.5 300 75% HPMA 25% AA 6.5 100 65% AA 35% tBuAC 1.23 400 2% HDDMA 50% AA 50% tBuAC 1.23 190 2% HDDMA 50% AA 25% HEMA 1.81 190 25% MA 2% HDDMA 90% AA 10% DMAEMA 9.6 322 2% HDDMA 65% AA 35% tBuAC 1.18 343 2% EGDMA 65% AA 35% tBuAC 1.27 286 2% BDDA 65% AA 35% tBuAC 1.5 382 2% PEGDA

TABLE-US-00002 TABLE 2 Viscosity Adhesion Composition used (mPa .Math. s) Force (N/cm) 34% MDP/66% tBuA 8.5 0.52 48% MDP/52% tBuA 17.4 0.56 55% MDP/45% tBuA 24.9 0.79 63% MDP/37% tBuA 40.8 0.82

Observation at the Scanning Electronic Microscope

[0073] The presence of the formed polymer has been observed, penetrated into the surface of the tissue over a depth of 50 m. Moreover, it has been observed that the formed polymer has penetrated into the spaces between the tissues' collagen fibres.

[0074] This observation indicates the capacity of the compositions according to the invention to penetrate into tissues which explains the perfect adhesion obtained.