SURGICAL GLUES BASED ON MONOMERS COMPRISING A PHOSPHATE FUNCTION

Abstract

A composition for use as a surgical adhesive for the adhesion of a material to a biological tissue, for the adhesion of biological tissues to one another, for the adhesion of a glue or of a substance to the surface of a biological tissue, as a surgical sealant, for blocking or plugging orifices created by a thread suture or staple suture or by a tissue resection, for blocking an orifice, an incision or a tear in a biological tissue, as a hemostatic agent for stopping bleeding, as a dressing on a biological tissue for covering and protecting a wound, for reinforcing a biological tissue, for attaching and stabilizing a biological tissue. The compositions include a polymerizable monomer with a phosphate function or a phosphonate function and a methacrylate function.

Claims

1-16. (canceled)

17. A composition for use as a surgical adhesive for the adhesion of a material to a non-mineralised biological tissue, for the adhesion of non-mineralised biological tissues to one another, for the adhesion of a glue or a substance to the surface of a non-mineralised biological tissue, as surgical sealant, for blocking or plugging orifices created by a thread suture or staple or by a tissue resection, for blocking an orifice, an incision or a tear in a non-mineralised biological tissue, as a haemostatic for stopping bleeding, as a dressing on a non-mineralised biological tissue for covering and protecting a wound, for reinforcing a non-mineralised biological tissue, for fixing and stabilising a non-mineralised biological tissue, wherein said composition comprises between 10 and 60% by mass relative to the total mass of the composition of a polymerisable monomer comprising a phosphate function or a phosphonate function and a methacrylate function.

18. The composition according to the claim 17, wherein the composition comprises a polymerisable monomer of formula I: ##STR00002## wherein: R2 is H or CH3; R1, R1′, and R1″ are independently of one another a linear polyether radical, a linear or branched aliphatic radical with C1-C50, an aromatic radical of C6-C18, for which the carbon chain of said radicals can be interrupted by O, S, OCONH and/or can comprise one or more alcohol functions; R1′ is H if c=0; R1″ is H if a=0; b is 1; and a or c is 1 or 0.

19. The composition according to claim 18, wherein a=0, R2=H or CH.sub.3 and R′1 and R1 is a linear aliphatic chain of C1-C12.

20. The composition according to claim 19, wherein a=0, c=0, R2=CH.sub.3 and R1 is a linear aliphatic chain of C1-C12.

21. The composition according to claim 17, wherein the polymerisable monomer of formula I is 10-MDP (C.sub.14H.sub.27O.sub.6P) or MEP(C.sub.12H.sub.19O.sub.8P).

22. The composition according to claim 17, further comprising between 4% and 30%, by mass in relation to the total mass of the composition, of a first cross-linking agent

23. The composition according to claim 21, further comprising between 30% and 90%, by mass in relation to the total mass of the composition, of a second cross-linking agent.

24. The composition according to claim 17, further comprising a co-monomer.

25. The composition according to claim 24, wherein said comonomer is selected from the group comprising polybutadiene diacrylates and mono or di-functional monomers such as tert-butyl acrylate, n-butyl acrylate, lauryl acrylate, lauryl methacrylate, methyl acrylate, stearyl methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, acrylic acid, methacrylic acid, 2-ethoxyethyl methacrylate, 2-ethylhexyl acrylate monomer, 2-ethylhexyl methacrylate, 2-phenyloxyethyl methacrylate, 1-(acryloyloxy)-3-(methacryloyloxy)-2-propanol, di(ethylene glycol) ethyl ether acrylate, ethyl acrylate, ethylene glycol methyl ether acrylate, ethylene glycol phenyl ether acrylate, methyl acrylate, 3-(trimethoxysilyl)propyl methacrylate, methyl methacrylate, poly(ethylene glycol) methyl ether acrylate (Mn of 200 to 10000 g/mol), triethylene glycol dimethacrylate, tert-butyl methacrylate, triethylene glycol monoethylether methacrylate, 3-(tris(trimethylsilyloxy)silyl)propyl methacrylate.

26. The composition according to claim 25, wherein said co-monomer has a concentration between 1 and 50% by mass in relation to the total mass of the composition.

27. The composition according to claim 17, further comprising a photoinitiator.

28. The composition according to claim 26, wherein said photoinitiator is selected from the group consisting of bisacylphosphine oxide (BAPO), Bis(.eta.5-2,4-cylcopentadien-1-yl)-bis(2,6-difluoro-3-(1H-pyrrol-1-yl)-phenyl) titanium (Irgacure 784), I′ 1-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), 2,4,6-trimethylbenzoyl-phenylphosphinate oxide (TPO-L), 2,4,6-trimethylbenzoyldiphenylphosphine oxide (TPO), 2,2-dimethoxyphenyl-2-acetophenone (DMPA), camphorquinone or 4,4′-bis(diethylamino)benzophenone, the latter associated with N-Phenylglycine (NPG), Ethyl-4-(dimethylamino)benzoate (EDB), N-Diisopropylethylamine (DIPEAN) and 4-(Dimethylamino)benzonitrile (DMABN).

29. The composition according to claim 26, wherein said photoinitiator is in a concentration between 0.2 and 10% by mass.

30. The composition according to claim 21, wherein the composition comprises between 0.1 and 5% by mass photoinitiator, between 30 and 90% by mass of a second cross-linking agent, between 10 and 50% by mass of polymerisable monomer comprising a phosphate function and a methacrylate function and between 1 and 50% by mass of co-monomer.

31. A non-invasive method for the adhesion of a material to a non-mineralised biological tissue, for the adhesion of non-mineralised biological tissues to one another, for the adhesion of a glue or a substance to the surface of a non-mineralised biological tissue, surgical sealing, for blocking or plugging orifices created by a thread suture or staple or by a tissue resection (haemostasis, aerostasis, lymphostasis for example), for blocking an orifice, an incision or a tear in a non-mineralised biological tissue, for stopping bleeding, for covering and protecting a wound, for reinforcing a non-mineralised biological tissue or for fixing and stabilising a non-mineralised biological tissue, said non-invasive method comprising the steps: (i) coating the tissue to be treated with a composition according to claim 17, (ii) letting the composition penetrate into said tissue, (iii) inducing the polymerisation of said composition.

Description

DESCRIPTION OF EMBODIMENTS

[0094] Materials and Methods

[0095] Skin Reaction Test

[0096] In Animals

[0097] Compositions according to the invention and control compositions were deposited on the backs and abdomens of previously shaved and disinfected rabbits and rats.

[0098] The composition is deposited on the surface of the skin and then polymerised using a light irradiation source.

[0099] The presence or absence of skin reactions is observed during the application and in the following days.

[0100] In Humans

[0101] Compositions according to the invention and control compositions were deposited on the front face of the forearm.

[0102] The composition is deposited on the surface of the skin and then polymerised by the source of polymerisation.

[0103] The presence or absence of skin reactions are observed during the application and in the following days.

[0104] In humans and animals, the following compositions were tested:

TABLE-US-00003 TABLE 3 TPO-L UDMA TEGDMA tBuA MDP LMA BM (%) (%) (%) (%) (%) (%) (%) AA 1.5 5 0 34.8 58.7 0 0.02 0 1.5 0 29.98 45.52 23.01 0 0.02 0 1.5 5 0 34.8 0 58.7 0.02 0 1.5 0 29.98 45.52 0 23.01 0.02 0 1.5 4.98 0 34.83 0.02 5870

[0105] Peeling Test

[0106] Compositions according to the invention and control compositions were deposited on bovine pericardium samples. This step is performed at 20° C. The said pericardium samples were subjected to UV radiation of 395 nm, for a duration of 45 s, in order to trigger the polymerisation of the monomers. The source of radiation was placed 10 cm from the pericardium.

[0107] The said pericardium samples were then covered with a 17-thread woven pad, which was then treated with a monomer solution identical to that used in the previous step.

[0108] The pericardium samples were subjected to UV radiation under the same conditions as in the previous step.

[0109] The resting time of the pad installed between the jaws of the traction machine is one minute, the temperature inside the sample is 30° C. + or −4° C. at the time of starting the test.

[0110] Results

[0111] Skin Reaction Test

[0112] All of the tests carried out on humans and animals with acrylic acid or methacrylic acid based compositions cause skin irritation and/or skin burns.

[0113] Rather, the tests carried out with compositions according to the invention comprising MDP and MEP (monomers with an acrylate function and a phosphate function) have shown an absence of apparent skin reactions.

[0114] These results clearly indicate that at an equivalent monomer concentration, the compositions according to the invention are less aggressive for the treated tissues.

[0115] Peeling Test

[0116] Of all the tests carried out, it was observed that the compositions comprising monomers without a phosphate function do not achieve good quality adhesion, i.e. peeling occurs at the interface between the skin and coated fibre web.

[0117] Rather, the compositions according to the invention, comprising a phosphate function and an acrylic function make it possible to obtain, regardless of the monomer concentration, good quality adhesion as evidenced by complete peeling in the treated tissue.

[0118] It is thus observed that, at an equivalent concentration and with a similar chemical structure, the presence of a phosphate function in the polymerisable monomer used in the composition according to the invention makes it possible to increase the resistance to rupture and ensures the cohesion by penetration into the surface layers of the tissue to be treated (i.e. the strength of the bond).