SURGICAL ADHESIVES

Abstract

A composition including a polymerizable monomer with a phosphate or phosphonate function on the one hand and a methacrylate, acrylate, acrylamide or methacrylamide function on the other hand at a concentration of between 5 and 40% by weight relative to the total weight of the composition,—a photoinitiator at a concentration of between 0.5 and 2% by weight, and a photopolymerizable resin.

Claims

1-11. (canceled)

12. A composition 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 at the surface of a non-mineralised biological tissue, as a surgical sealant, to seal or plug orifices created by wire or staple suture or by tissue resection, to seal an orifice, an incision or a tear in a non-mineralised biological tissue, as a haemostatic to stop bleeding, as a dressing on a non-mineralised biological tissue to cover and protect a wound, to reinforce a non-mineralised biological tissue, to fix and stabilize a non-mineralised biological tissue comprising: a polymerisable monomer comprising a phosphate or phosphonate function on the one hand and a methacrylate, acrylate, acrylamide or methacrylamide function on the other hand at a concentration comprised between 5 and 40% by weight relative to the total weight of the composition, a photoinitiator at a concentration comprised between 0.5 and 2% by weight, and a photopolymerisable resin.

13. The composition according to claim 12, wherein said polymerisable monomer is selected from the group consisting of molecules having the CAS number [14206-25-8], [14235-57-5], [86242-61-7], [932019-41-6], [1980781-17-6], [60161-88-8], [87243-97-8], [1980048-95-0], [918802-80-9], [63411-25-6], [1980064-07-0], [22432-83-3], [1980781-08-5], [252210-28-9], [1114567-37-1], [80730-17-2], [518991-74-7], [87243-96-7], [1980062-84-7], [518991-75-8], [252210-30-3], [22432-84-4], [727415-30-7], [727415-31-8], [784139-89-5] or [1194231-98-5] and mixtures thereof.

14. The composition according to claim 12, wherein said polymerisable monomer is of formula I ##STR00002## wherein R2 is H or CH3; R1, R1′, R1″ are independently of each other a linear polyether radical, a linear or branched C1-C50 aliphatic radical, a C6-C18 aromatic radical, wherein the carbon chain of said radicals may be interrupted by O, S, OCONH and/or may comprise one or more alcohol function(s); R1′ is H if c=0; R1′ is H if a=0; b is 1; a or c is 1 or 0.

15. The composition according to claim 14, wherein a=0, R2=H or CH3 and R′ 1 and R1 is a linear C1-C12 aliphatic chain.

16. The composition according to claim 15, wherein a=0, c=0, R2=CH3 and R1 is a linear C1-C12 aliphatic chain.

17. The composition according to claim 12, wherein the polymerisable monomer of formula I is 10-MDP (C14H27O6P) or MEP (C12H19O8P).

18. The composition according to claim 17, characterized in that said polymerisable monomer has a concentration comprised between 25 and 35% by weight relative to the total weight of the composition.

19. The composition according to claim 12, wherein said photoinitiator is capable of inducing a polymerisation under the effect of radiation comprised between 350 and 520 nm.

20. The composition according to claim 12, wherein said photoinitiator is selected from the group consisting of 2,4,6-trimethylbenzoyl-phenylphosphinate oxide (TPO-L), camphorquinone or 4,4′ - bis(diethylamino)benzophenone, the latter associated with Ethyl-4-(dimethylamino)benzoate (EDB), and mixtures thereof.

21. The composition according to claim 12, wherein it comprises between 0.25 and 2% by weight of said photoinitiator, between 50 and 90% by weight of said photopolymerisable resin and between 20 and 40% by weight of said polymerisable monomer.

22. A non-invasive method for covering and protecting a cutaneous lesion, comprising the steps of: (i) coating the tissue to be treated with a composition according to claim 12, (ii) inducing the polymerisation of said composition.

Description

DETAILED DESCRIPTION

Cutaneous Reaction Test in Humans

[0098] Compositions according to the invention have been deposited over the palm. The composition is deposited at the surface of the skin and then polymerised by UV radiation.

[0099] The presence or absence of cutaneous reactions are observed during set-up and then in the days that follow.

Optimisation of the Photoinitiator Concentration

[0100] Tests have been performed with compositions according to the invention comprising 30% of MEP, 69.5% of Ebecryl 230 and variable concentrations of TPO-L.

[0101] A poor hold over time of the bonds and an extension of the photopolymerisation time (>20 s) incompatible with use of the composition are observed for photoinitiator concentrations lower than 0.5%.

[0102] An exothermic polymerisation incompatible with use of the compositions in vivo is also observed for concentrations higher than 2%.

Optimisation of the Photopolymerisation Irradiance I0

[0103] Tests have been performed with compositions according to the invention comprising 30% of MEP, 69.5% of Ebecryl 230 and 1% of TPOL.

[0104] These compositions have been used according to the previously-described protocol and subjected to a radiation with a UV source at 395 nm with variable irradiances.

[0105] The lower limit of the irradiance (17 mW/cm2) is limited by the kinetics of polymerisation and the inhibition by oxygen of the reaction. The upper limit of the irradiance (92 mW/cm2) is limited by the exothermic reaction. Nonetheless, irradiance values between 10 and 100 mW/cm2 allow for acceptable results.

Effectiveness of the Compositions According to the Invention

[0106] The qualitative evaluation of the In Vivo adhesion and the quality of the bonding has been evaluated on human skin (N=1 to 3 tests). A qualitative adherence scale has been developed:

[0107] 0: no adhesion at t=0, no anchorage

[0108] 1: adhesion at t=0, very weak anchorage, detachment in a few minutes, no resistance to stress

[0109] 2: adhesion at t=0, weak anchorage, hold<1 h, no resistance to stress, rapid detachment on the edges

[0110] 3: adhesion at t=0, weak anchorage, hold 2 h to 4 h, low resistance to stress, rapid detachment on the edges

[0111] 4: adhesion at t=0, weak anchorage, hold 4 h to 8 h, low resistance to stress, rapid detachment on the edges

[0112] 5: adhesion at t=0, average anchorage, hold 4 h to 8 h, average resistance to stress, resistance to detachment on the edges

[0113] 6: adhesion at t=0, average anchorage, hold 8 h to 12 h, average resistance to stress, resistance to detachment on the edges

[0114] 7: adhesion at t=0, average anchorage, hold 12 h to 24 h, good to average resistance to stress, good resistance to detachment on the edges

[0115] 8: adhesion at t=0, good anchorage, hold 24 h to 36 h, good resistance to stress, good resistance to detachment on the edges

[0116] 9: adhesion at t=0, good anchorage, hold 36 h to 48 h, very good resistance to stress, good resistance to detachment on the edges

[0117] 10: adhesion at t=0, excellent anchorage, hold>48 h, excellent resistance to stress, no detachment at the edges.

[0118] All of the results obtained with the TPO-L+MEP+Ebecryl 230 combination are reported in Table 1.

[0119] A statistical processing of these data has revealed a major influence of the concentration of photoinitiator and adhesive monomer on adhesion and holding properties. The higher these concentrations, the greater the adhesive properties will be. On the contrary, low concentrations lead to lower adhesion and holding levels. The irradiance of the LED UV source (at 399 nm) also affects the adhesive properties of the bonds. Moreover, the obtained sensitiveness to water of each of the adhesion layers was compatible with the use of the compositions in the method according to the invention.

TABLE-US-00001 TABLE 1 [Ebecryl [TPOL] (MEP] 230] I0 In vivo % wt % wt % wt (mW/cm.sup.2) hold Pelage @ time Exothermics Flexibility 1 30 69 17 to 20 8 6.2 <20 s +++ ++ 0.5 20 79 17 to 20 3 N/D <20 s 0 +++ 0.5 20 79 92 4 1.1 <20 s 0 ++ 0.5 40 59 17 to 20 7 N/D <20 s 0 ++ 0.5 40 59 92 6 2.3 <20 s 0 + 2 20 79 17 to 20 6 N/D <20 s + +++ 2 20 79 92 7 0.8 <20 s + ++ 2 40 59 17 to 20 8 N/D <20 s +++ +

[0120] [Table 1] represents the experimental results on the TPOL+MEP+Ebecryl 230 formulation.

[0121] The results obtained in Table 2 show that the adhesive monomer concentration can also be lowered to 5%.

TABLE-US-00002 TABLE 2 [Ebecryl [TPOL] (MEP] 230] I0 In vivo % wt % wt % wt (mW/cm.sup.2) hold @ time Exothermics Flexibility 1 30 69 17 to 20 8 <20 s +++ ++ 0.25 40 59.75 20 2 20 s < t.sub.@ < 40 s + + 0.1 40 59.9 20 2 40 s < t.sub.@ < 60 s + ++ 0.5 30 69.5 20 5 <20 s 0 ++ 1 25 74 20 8 <20 s +++ ++ 1 5 94 20 1 <20 s 0 +++ 1 10 89 20 2 <20 s 0 +++ 1 20 79 20 2 <20 s + ++

[0122] [Table 2] represents the complementary experimental results on the TPOL+MEP+Ebecryl 230 formulation.