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. A monomer that is polymerisable under the effect of ultraviolet (UV) radiation and in that the viscosity of said composition is less than 10 mPa.Math.s at 20° C.

Claims

1. A composition, intended to be used in a method 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, comprising: a monomer polymerisable under the effect of ultra-violet (UV) radiation, wherein said composition viscosity is less than 10 mPa.Math.s at 20°, wherein the composition is not a hydrogel, wherein the composition is an adhesive for inducing the adhesion of biological tissues to one another, and wherein said monomer has a concentration of between 90 and 100% in mass in relation to the total mass of the composition.

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

3. The composition according to claim 1, wherein the composition does not comprise polymerisable monomers of which the polymerisation can be initiated just by the contact of water molecules.

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

5. The composition according to claim 1, wherein the composition's viscosity is less than 6 mPa.Math.s at 20° C.

6. The composition according to claim 1, wherein the composition's viscosity is less than 2 mPa.Math.s at 20° C.

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

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

9. The composition according to claim 8, wherein said polar function is chosen in the group comprising hydroxyl, amide, carboxyl, amino, carbonate, carbamate, sulphonamide, sulphonic, phosphonic, methoxyethyl, methoxyethoxyethyl, hydroxyethyl and hydroxyethoxyethyl functions.

10. The composition according to claim 8, wherein said monomer is chosen in the group comprising the mono-, di-, tri-, tetra- and penta-acrylate or methacrylate, and their mixtures.

11. The composition according to claim 7, 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 sulphur (4-methacryloylthiophenyl); tert-butyl acrylate; an ethyleneglycol or a polyethyleneglycol chosen in the group composed of acrylate, methacrylate; diacrylate, dimethacrylate and their mixtures.

12. The composition according to claim 7, 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.

13. The composition according to claim 1, wherein said monomer has a molar mass of between 50 and 300g.Math.mol-1.

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

15. The composition according to claim 1, wherein the composition further comprises a cross-linking agent.

16. The composition according to one of claim 15, wherein said cross-linking agent is present at a concentration of between 1% and 3% in mass in relation to the total mass of the composition.

17. The composition according to one of claim 15, wherein said cross-linking agent is present at a concentration of between 1% and 2% in mass in relation to the total mass of the composition.

18. The composition according to claim 15, wherein said cross-linking agent comprises an acrylate function.

19. The composition according to claim 15, wherein said cross-linking agent is chosen in the group comprising multifunctional acrylates comprising 1,6-hexanediol dimethylacrylate (HDDMA), ethylene glycol dimethylacrylate (EGDMA), 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 one of claim 15, wherein said cross-linking agent is present at a concentration of between 1% and 5% in mass in relation to the total mass of the composition.

21. The composition according to one of claim 1, wherein the composition further comprises 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 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 1% in mass.

24. A non-invasive method 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 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, comprising: the steps: (i) coating the tissue to treat with a composition according to claim 1, (ii) letting the composition penetrate into said tissue, (iii) inducing, by UV radiation, the polymerisation of said composition.

25. The method according to claim 24, further comprising: (iv) appositioning a synthetic tissue to the surface of said 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 100W and 200W.

28. Kit of parts comprising a composition according to claim 1 and a UV radiation source.

29. The composition according to claim 1, wherein said UV ray has a wavelength of between 170 nm and 260 nm.

30. The composition according to claim 1, wherein said UV ray has a wavelength of between 190 nm and 240 nm.

31. The composition according to claim 21, wherein said photoinitiator is at a concentration of between 0.2% and 0.3% in mass.

Description

(1) 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.

(2) 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.

(3) The pericardium samples have been subjected to UV radiation under the identical conditions as those in the preceding step.

(4) A peeling test has then been carried out by traction at 180° C. 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.

(5) 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.

(6) The pericardium samples have then been transversally cut and observed by scanning electronic microscopy.

(7) The results obtained are presented in the table below.

(8) 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.

(9) It has been observed that the resistance to rupture (that is, the resistance to the bonding), increases inversely to the viscosity, of the composition according to the invention, used.

(10) TABLE-US-00001 TABLE 1 Composition used (all Resistance to compositions rupture F/b comprise 0.25% Viscosity [N/m] in the in DMPA mass) [mPa .Math. s] pericardium 100% acrylic 1 300 acid 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

(11) The presence of the formed polymer has been observed, penetrated into the surface of the tissue over a depth of 50 μm. Moreover, it has been observed that the formed polymer has penetrated into the spaces between the tissues' collagen fibres.

(12) This observation indicates the capacity of the compositions according to the invention to penetrate into tissues which explains the perfect adhesion obtained.