阅读说明：本技术 基于包含磷酸酯官能团的单体的外科胶水 (Surgical glues based on monomers comprising phosphate functional groups ) 是由 伯特兰德·佩兰 艾丽安·奥班 雅克·拉利维 让-菲利普·施韦贝伦 于 2020-02-19 设计创作，主要内容包括：本发明涉及一种组合物,其用作：外科粘合剂,用于将材料粘合到生物组织、用于将生物组织彼此粘合、用于将胶水或物质粘合到生物组织的表面；外科密封剂,用于封闭或堵塞由线缝合或钉缝合或者由组织切除产生的孔口、用于封闭生物组织中的孔口、切口或撕裂；止血剂,用于止血；生物组织上的敷料,用于覆盖和保护伤口、用于加强生物组织、用于附着和稳定生物组织；其特征在于所述组合物包含可聚合单体,其包含磷酸酯官能团或膦酸酯官能团和甲基丙烯酸酯官能团。(The present invention relates to a composition for use as: surgical adhesives for adhering materials to biological tissues, for adhering biological tissues to each other, for adhering glues or substances to the surface of biological tissues; surgical sealants for closing or blocking apertures created by suture or staple suturing or by tissue resection, for closing apertures, incisions or tears in biological tissue; a hemostatic agent for hemostasis; dressings on biological tissue for covering and protecting wounds, for reinforcing biological tissue, for attaching and stabilizing biological tissue; characterised in that the composition comprises a polymerisable monomer comprising a phosphate functional group or a phosphonate functional group and a methacrylate functional group.)

1. A composition for use as: a surgical adhesive for adhering materials to biological tissue, for adhering biological tissues to each other, for adhering glue or substances to the surface of biological tissue; surgical sealants for closing or blocking apertures created by suture or staple suturing or by tissue resection, for closing apertures, incisions or tears in biological tissue; a hemostatic agent for hemostasis; dressings on biological tissue for covering and protecting wounds, for reinforcing biological tissue, for fixing and stabilizing biological tissue; characterized in that the composition comprises a polymerizable monomer comprising a phosphate function or a phosphonate function and a methacrylate function.

2. Composition according to the preceding claim, characterized in that it comprises a polymerizable monomer of formula I, wherein

-R2 is H or CH 3;

r1, R1', R1 "are independently of each other a linear polyether group, a linear or branched aliphatic group having C1-C50, an aromatic group having C6-C18, wherein the carbon chain of said groups can be interrupted by O, S, OCONH and/or can comprise one or more alcohol functions;

if c is 0, then R1' is H;

if a is 0, then R1 "is H;

b is 1;

a or c is 1 or 0.

3. Composition according to the preceding claim, characterized in that a is 0, R2 is H or CH₃And R'1 and R1 are linear aliphatic chains of C1-C12.

4. Composition according to the preceding claim, characterized in that a-0, c-0, R2-CH₃And R1 is a linear aliphatic chain of C1-C12.

5. The composition of claim 1, wherein the polymerizable monomer of formula I is 10-MDP (C)₁₄H₂₇O₆P) or MEP (C)₁₂H₁₉O₈P)。

6. Composition according to any one of the preceding claims, characterized in that the concentration of the polymerizable monomer is between 10% and 60% by mass relative to the total mass of the composition.

7. Composition according to any one of the preceding claims, characterized in that it further comprises between 4% and 30% by mass of a first cross-linking agent, relative to the total mass of the composition.

8. Composition according to claim 7, characterized in that it further comprises between 30% and 90% by mass of a second cross-linking agent, relative to the total mass of the composition.

9. Composition according to any one of the preceding claims, characterized in that it further comprises a comonomer.

10. Composition according to the preceding claim, characterized in that the comonomer is selected from the group comprising: polybutadiene diacrylates and mono-or difunctional monomers such as t-butyl acrylate, n-butyl acrylate, lauryl methacrylate, methyl acrylate, stearyl methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, acrylic acid, methacrylic acid, 2-ethoxyethyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, 2-phenoxyethyl 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) acrylate, poly (ethylene glycol) acrylate), poly (ethylene glycol) acrylate), poly (ethylene glycol) acrylate), poly (ethylene glycol) acrylate), poly (butylene (ethylene glycol) acrylate), poly (butylene (ethylene (butylene (styrene), poly (butylene (ethylene (butylene (styrene), poly (butylene (styrene), poly (ethylene glycol) acrylate), poly (styrene), poly (ethylene glycol) acrylate), poly (styrene), poly (ethylene glycol) methyl ether acrylate (Mn 200 to 10000g/mol), triethylene glycol dimethacrylate, tert-butyl methacrylate, triethylene glycol monoethyl ether methacrylate, 3- (tris (trimethylsiloxy) silyl) propyl methacrylate.

11. Composition according to the preceding claim, characterized in that the concentration of said comonomer is between 1 and 50% by mass relative to the total mass of the composition.

12. Composition according to any one of claims 1 to 11, characterized in that it further comprises a photoinitiator.

13. The composition according to claim 12, characterized in that the photoinitiator is selected from the group comprising: bisacylphosphine oxide (BAPO), bis (. eta. 5-2, 4-cyclopentadien-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-propan-1-one (Irgacure 2959), 2,4, 6-trimethylbenzoyl-phenylphosphinate oxide (TPO-L), 2,4, 6-trimethylbenzoyl diphenylphosphine oxide (TPO), 2-dimethoxyphenyl-2-acetophenone (DMPA), camphorquinone or 4,4' -bis (diethylamino) benzophenone, the latter is associated with N-phenylglycine (NPG), ethyl 4- (dimethylamino) benzoate (EDB), N-Diisopropylethylamine (DIPEAN) or 4- (dimethylamino) benzonitrile (DMABN).

14. The composition according to any one of claims 12 to 13, characterized in that the concentration of the photoinitiator is between 0.2 and 10 mass%.

15. Composition according to claim 7, characterized in that it comprises between 0.1% and 5% by mass of photoinitiator, between 30% and 90% by mass of second cross-linking agent, between 1% and 50% by mass of polymerizable monomer comprising phosphate and methacrylate functional groups and between 1% and 50% by mass of comonomer.

16. A non-invasive method for adhering materials to biological tissues, for adhering biological tissues to each other, for adhering glues or substances to the surfaces of biological tissues, surgical sealing, for closing or blocking orifices created by suture or staple suturing or by tissue resection (e.g. haemostasis, stagnation of qi, lymph stasis), for closing orifices in biological tissues, incisions or tears, for haemostasis, for covering and protecting wounds, for reinforcing biological tissues or for fixing and stabilizing biological tissues, notably comprising the steps of:

- (i) coating the tissue to be treated with a composition according to any one of claims 1 to 15,

- (ii) allowing said composition to penetrate into said tissue,

- (iii) inducing the polymerization of the composition.

Technical Field

The invention particularly relates to compositions for use as surgical adhesives, surgical sealing products, hemostatic dressings, and skin dressings. More specifically, the invention relates to a composition intended for use in a method:

-as a surgical adhesive for adhering a material to biological tissue,

for the biological tissues to adhere to one another,

-a glue or substance for adhering to a surface of a biological tissue,

-as a surgical sealant,

for closing or blocking orifices created by suture or staple suturing or by tissue resection (e.g. haemostasis, stagnation of qi, lymph stasis),

for closing an aperture, cut or tear in biological tissue,

-as a haemostat, for haemostasis, alone or in combination with conventional haemostatic techniques such as suturing, compression or electrocoagulation,

as a dressing on biological tissue for covering and protecting wounds,

these compositions may also be used:

-for the augmentation of biological tissue,

for fixing and stabilizing biological tissues.

Background

Many surgical techniques involve the use of surgical glues. The latter is mainly used to help achieve surgical hemostasis. However, the efficacy of surgical glues in this indication is controversial, and other uses such as air stagnation have not shown much better.

Furthermore, surgical glues have very poor adhesive properties and therefore cannot be used as adhesives or surgical sutures. Surgical glues are mostly applied directly to the tissue without the need to prepare the adhesive surface. The penetration into the tissue is poor or non-existent, which results in poor quality of the bond. The applicant has verified that current glues do not stick nor penetrate into the tissue.

To solve this problem, low viscosity surgical glues have been proposed. These surgical glues penetrate more easily into the tissue and thus provide a better bond. However, these surgical glues require a high concentration of monomers. In addition, their chemical nature can cause burns at the site of application.

The present invention therefore proposes to provide a new type of surgical glue. The composition and the process according to the invention make it possible to obtain an effective and strong bond with a lower monomer amount than the glues of the prior art. Furthermore, in contrast to the glues of the prior art, the surgical glue according to the invention does not cause burns to the skin.

Disclosure of Invention

The invention particularly relates to compositions for use as surgical adhesives, surgical sealing products, hemostatic dressings, and skin dressings. More specifically, the present invention relates to compositions for use as: surgical adhesives for adhering materials to biological tissues, for adhering biological tissues to each other, for adhering glues or substances to the surface of biological tissues; surgical sealants for closing or blocking apertures created by suture or staple suturing or tissue resection, for closing apertures, incisions or tears in biological tissue; a hemostatic agent for hemostasis; dressing on biological tissue, for covering and protecting wounds, for reinforcing biological tissue, for fixing and stabilizing biological tissue, it being noted that the composition comprises a polymerizable monomer comprising phosphate or phosphonate functions and methacrylate functions.

According to a preferred embodiment of the invention, the polymerizable monomer comprises a phosphate function and a methacrylate function.

The applicant has been able to demonstrate that the presence of phosphate functions or phosphonates in the monomers makes it possible to obtain compositions which have adhesive capacity and are safer than compositions comprising chemically equivalent monomers comprising methacrylate functions but which do not contain phosphate functions.

Preferably, the polymerizable monomer has the formula I, wherein [ chemical formula 1],

r2 is H or CH 3;

r1, R1', R1 "are independently of one another a linear polyether group, a linear or branched aliphatic group of C1 to C50, an aromatic group of C6 to C18, wherein the carbon chain of said groups may be interrupted by O, S, OCONH and/or may comprise one or more alcohol functions;

if a is 0, then R1 "is H;

b is 1;

a or c is 1 or 0.

The term "the carbon chain of said functional group may be interrupted" means that said functional group is inserted into the carbon chain, i.e. is attached to carbon atoms on both sides.

Preferably, a is 0, R2 is H or CH₃And R'1 and R1 are linear aliphatic chains of C1-C12.

Even more preferably, a is 0, c is 0, R2 is CH₃And R1 is a linear aliphatic chain of C1-C12.

Preferably, a is 0, C is 0, R "1 is H, R'1 is H, R1 is a linear aliphatic chain of C1-C12, b is 1, R2 is CH₃。

Preferably, a is 1, C is 1, b is 0, R1 is H, R'1 is a linear aliphatic chain R "1 is C1-C12, R2 is CH 2₃。

Preferably, the polymerizable monomer of formula I is 10-MDP (C)₁₄H₂₇O₆P) or MEP (C)₁₂H₁₉O₈P)。

According to another preferred embodiment, the polymerizable monomer of formula I is selected from the group consisting of glycerol dimethacrylate phosphate, ethylene glycol methacrylate phosphate, polyethylene glycol methacrylate phosphate, methacryloxy decyl hydrogen phosphate, methacryloxy ethoxy hydrogen phosphate, glycerol monomethacrylate phosphate, triethylene glycol monomethacrylate phosphate, methacryloxy propyl ester phosphate, methacryloxy hexyl phosphate, aminoethyl methacrylate phosphate, bis (glyceryl dimethacrylate) phosphate and mixtures thereof.

In the context of the present invention, the term "polymerizable monomer" is meant to designate a monomer whose polymerization can be initiated by a physical or chemical activator.

According to a preferred embodiment, the polymerization is initiated by the action of UV radiation. In a preferred manner, the wavelength of said UV radiation is between 200nm and 400nm, even more preferably between 300nm and 400nm and most preferably between 350nm and 400 nm.

According to another preferred embodiment, the polymerization is initiated by the action of radiation having a wavelength between 400nm and 500 nm.

According to a preferred embodiment, the polymerization is initiated by a chemical activator.

The polymer obtained after polymerization of the monomers is preferably a biocompatible polymer.

Preferably, the viscosity of the composition according to the invention is less than 200mpa.s at 20 ℃.

The viscosity of the composition can be measured in particular by a falling ball viscometer according to standard DIN 53015.

According to a preferred embodiment, the viscosity is less than 120mpa.s at 20 ℃.

According to an even more preferred embodiment, the viscosity is less than 50mpa.s at 20 ℃.

According to a much preferred embodiment, the viscosity is less than 20mpa.s at 20 ℃.

According to a preferred embodiment, the composition according to the invention is not a hydrogel.

According to a preferred embodiment, the molar mass of the monomers is between 250 and 500g.mol^-1In the meantime.

According to a preferred embodiment, the concentration of said monomer is between 10 and 60% by mass relative to the total mass of the composition.

According to an even more preferred embodiment, the concentration of said monomer is between 40 and 90% by mass relative to the total mass of the composition.

According to a preferred embodiment, the composition further comprises between 4 and 30 mass% of a first cross-linking agent, relative to the total mass of the composition.

The person skilled in the art will be able to select the most suitable cross-linking agent depending on the polymerizable monomer used.

According to a preferred embodiment, the first crosslinking agent comprises acrylate-functional groups or methacrylate-functional groups.

According to a preferred embodiment, the first cross-linking agent is selected from the group comprising multifunctional acrylates and methacrylates, in particular comprising 1, 6-hexanediol diacrylate, trimethylolpropane triacrylate, 1, 2-ethylene glycol dimethacrylate, pentaerythritol tetraacrylate, I3- (acryloyloxy) -2-hydroxypropyl methacrylate (AHM), Urethane Dimethacrylate (UDMA), hexanediol dimethacrylate (HDDMA), triethylene glycol dimethacrylate (TEGDMA) and mixtures thereof.

According to another preferred embodiment, the first crosslinker is selected from the group comprising multifunctional acrylates, in particular comprising hexanediol dimethacrylate (HDDMA), Ethylene Glycol Dimethacrylate (EGDMA), butanediol diacrylate (BDDA), poly (ethylene glycol) diacrylate (PEGDA) and mixtures thereof.

According to a preferred embodiment, said first crosslinking agent is UDMA and is present in a concentration of between 4.5% and 5% by mass relative to the total mass of the composition.

According to a preferred embodiment, said first crosslinking agent is TEGDMA and is present in a concentration of between 25% and 30% by mass relative to the total mass of the composition.

According to another preferred embodiment, the composition further comprises between 30 and 90 mass% of a second cross-linking agent relative to the total mass of the composition.

According to another preferred embodiment, said second crosslinking agent is selected from the group comprising multifunctional poly (ethylene glycol) acrylates (functionality 2-4), in particular SR415, SR610 and Ebecryl11 and mixtures thereof.

According to another preferred embodiment, said second crosslinking agent is selected from the group comprising difunctional urethane acrylate aliphatic resins, in particular Ebecryl 4491, Ebecryl 230, Ebecryl 271, Ebecryl 2221 and CN 9002.

According to another preferred embodiment, said second crosslinking agent is selected from the group comprising difunctional acrylic urethane aromatic resins, in particular Ebecryl 210 and mixtures thereof.

According to another preferred embodiment, said second crosslinker is selected from the group comprising difunctional epoxy acrylate resins, in particular EB 3639.

According to another preferred embodiment, said second cross-linking agent is selected from the group comprising acrylic resins, in particular Ebecryl 8296, Ebecryl 8232, Ebecryl ODA, Ucecoat 6569 and mixtures thereof.

For the sake of clarity, it is stated that some of the polymerizable monomers according to the invention can act as crosslinkers and in the latter case the above preferred concentrations are irrelevant.

According to a preferred embodiment, the composition further comprises a comonomer.

According to an even more preferred embodiment, said comonomer is selected from the group comprising: polybutadiene diacrylates and mono-or difunctional monomers such as t-butyl acrylate, n-butyl acrylate, lauryl methacrylate, methyl acrylate, stearyl methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, acrylic acid, methacrylic acid, 2-ethoxyethyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, 2-phenoxyethyl 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) acrylate, poly (ethylene glycol) acrylate), poly (ethylene glycol) acrylate), poly (ethylene glycol) acrylate), poly (ethylene glycol) acrylate), poly (butylene (ethylene glycol) acrylate), poly (butylene (ethylene (butylene (styrene), poly (butylene (ethylene (butylene (styrene), poly (butylene (styrene), poly (ethylene glycol) acrylate), poly (styrene), poly (ethylene glycol) acrylate), poly (styrene), poly (ethylene glycol) methyl ether acrylate (Mn 200 to 10000g/mol), triethylene glycol dimethacrylate, tert-butyl methacrylate, triethylene glycol monoethyl ether methacrylate, 3- (tris (trimethylsiloxy) silyl) propyl methacrylate.

According to a preferred embodiment, the concentration of said comonomer present in the composition according to the invention is between 1 and 50% by mass relative to the total mass of the composition.

According to a preferred embodiment, the composition according to the invention comprises a photoinitiator. The person skilled in the art will select the most suitable photoinitiator depending on the emission spectrum of the light used.

The photoinitiator may be chosen in particular from: bisacylphosphine oxide (BAPO), bis (. eta. 5-2, 4-cyclopentadien-1-yl) -bis (2, 6-difluoro-3- (1H-pyrrol-1-yl) -phenyl) titanium (Irgacure 784), 1- [4- (2-hydroxyethoxy) -phenyl ] -2-hydroxy-2-methyl-1-propan-1-one (Irgacure 2959), 2,4, 6-trimethylbenzoyl-phenylphosphinate oxide (TPO-L), 2,4, 6-trimethylbenzoyl diphenylphosphine oxide (TPO), 2-dimethoxyphenyl-2-acetophenone (DMPA), camphorquinone or 4,4' -bis (diethylamino) benzophenone, the latter are associated with N-phenylglycine (NPG), ethyl 4- (dimethylamino) benzoate (EDB), N-Diisopropylethylamine (DIPEAN) or 4- (dimethylamino) benzonitrile (DMABN).

Advantageously, the photoinitiator is used in a concentration between 0.2 and 10% by mass.

According to a preferred embodiment, the photoinitiator is TPO-L.

According to another preferred embodiment, the polymerization is initiated by a chemical activator, and more specifically by benzoyl peroxide in association with N-phenylglycine (NPG), ethyl 4- (dimethylamino) benzoate (EDB), N-Diisopropylethylamine (DIPEAN) or 4- (dimethylamino) benzonitrile (DMABN).

Advantageously, the chemical activator is used in a concentration between 0.5 and 3 mass%.

According to a preferred embodiment, the composition comprises only the monomer and the photoinitiator or only the monomer, the first or second crosslinker and the photoinitiator.

According to an embodiment of the invention, the composition comprises a solvent, even more preferably the solvent is water. According to another preferred embodiment, the solvent is an alcohol, and more preferably ethanol or isopropanol.

According to another preferred embodiment, the composition is solvent-free.

According to a preferred embodiment of the invention, the composition comprises a plug (plug). According to an even more preferred embodiment, the plug is a basic plug and in a very preferred manner the basic plug is selected from the group comprising: KOH, guanidine carbonate, Ca (OH)₂、K₂CO₃2-amino-2-methyl-1-propanol (AMP), Na₂CO₃Resorcinol and NaOH.

The person skilled in the art must also select the concentration of the plug that is most suitable for this purpose. According to a much preferred embodiment of the invention, the composition comprises KOH in a concentration between 0 and 8 mass%.

According to a preferred embodiment of the invention, the composition comprises between 0.1 and 5% by mass of photoinitiator, between 30 and 90% by mass of second crosslinking agent, between 1 and 50% by mass of polymerizable monomer according to the invention comprising phosphate and methacrylate functional groups and between 1 and 50% by mass of comonomer.

More particularly preferred are the compositions described in the table below (amounts are given as percentages of the total mass of the composition).

[ Table 1]

[ Table 2]

In the context of the present invention, the term "comprising" means that the composition according to the invention comprises the cited elements. In a preferred manner, the invention relates to a composition comprising only the cited elements, excluding any other elements.

The invention also relates to a non-invasive method for adhering materials to biological tissues, for adhering biological tissues to each other, for adhering glues or substances to the surface of biological tissues, for surgical sealing (e.g. haemostasis, stagnation of qi, lymph stasis) for closing or blocking orifices created by suture or staple suturing or by tissue resection, for closing orifices in biological tissues, incisions or tears, for haemostasis, for covering and protecting wounds, for reinforcing biological tissues or for fixing and stabilizing biological tissues, notably comprising the following steps:

- (i) coating the tissue to be treated with a composition according to the invention

- (ii) allowing the composition to penetrate into said tissue,

- (iii) inducing polymerization of the composition.

In the context of the present invention, the term "biological tissue" preferably means non-mineralized biological tissue.

For the sake of clarity, it is explicitly pointed out that in the context of the present invention, the term "biological tissue" does not refer to bones and teeth.

The method according to the invention is advantageously non-invasive. The term "non-invasive" means that the method according to the invention does not comprise any surgical step consisting of approaching the tissue to be treated. Thus, the method according to the invention is performed on biological tissue that is directly accessible (e.g. skin) or previously accessible by other methods.

According to a preferred embodiment, said step (iii) is carried out by means of UV radiation. The characteristics of the UV radiation used, in particular its power and wavelength, are adapted to the ingredients of the composition, in particular to the nature of the polymerizable monomers and their concentration in the composition.

According to another preferred embodiment, said step (iii) is performed by visible light radiation.

According to a preferred embodiment, the wavelength of the UV radiation is between 350 and 400 nm.

According to a preferred embodiment, the irradiation power of the UV radiation is between 20mW/cm2 and 500mW/cm 2.

The invention also relates to an assembly comprising a composition according to the invention and a component of a UV radiation source. Preferably, the UV radiation source of the assembly of parts may emit UV radiation suitable for polymerizing and/or assisting in polymerizing and/or accelerating the polymerization of the polymerizable monomers of the composition.

According to another embodiment, the invention also relates to an assembly of parts comprising a composition according to the invention and an initiator of chemical polymerization.

In the context of the present invention, the term "UV radiation source" refers to any artificial means capable of generating UV radiation and more particularly UV radiation having a wavelength between 200 and 400nm, even more preferably between 300 and 400nm and especially preferably between 350 and 400 nm. In a preferred manner, said UV radiation is an irradiation power of between 20mW/cm2 and 500mW/cm2 and even more preferably between 50mW/cm2 and 150mW/cm 2.

In a more preferred manner, the UV radiation has a wavelength between 350 and 400nm and a power between 50-200mW/cm 2.

Detailed Description

Materials and methods

Skin reaction test

In animals

The compositions according to the invention and the control compositions were deposited on the backs and abdomen of previously shaved and disinfected rabbits and rats.

The composition is deposited on the skin surface and then polymerized using a light radiation source.

The presence or absence of skin reactions was observed during the application and for the following days.

In a human being

The composition according to the invention and the control composition were deposited on the front side of the forearm.

The composition is deposited on the skin surface and then polymerized by the polymerization source.

The presence or absence of skin reactions was observed during the application and for the following days.

In humans and animals, the following compositions were tested:

TABLE 3

Peel test

The compositions according to the invention and the control compositions were deposited on bovine pericardial samples. This step is carried out at 20 ℃. The pericardial sample was subjected to UV radiation at 395nm for 45 seconds in order to trigger polymerization of the monomers. The radiation source was placed 10cm from the pericardium.

The pericardial sample was then covered with a 17-wire woven pad, which was then treated with the same monomer solution as used in the previous step.

The pericardial sample was subjected to uv radiation under the same conditions as the previous step.

The rest time of the pad installed between the tractor jaws was 1 minute and the internal temperature of the sample at the start of the test was 30 ℃ + or-4 ℃.

Results

Skin reaction test

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

In contrast, tests carried out with compositions comprising MDP and MEP (monomers having acrylate and phosphate functional groups) according to the present invention showed the absence of significant skin reactions.

These results clearly show that at equivalent monomer concentrations, the compositions according to the invention are less aggressive towards the treated tissue.

Peel test

In all the tests carried out, it was observed that the compositions comprising monomers not having a phosphate function did not achieve good quality adhesion, i.e. peeling occurred at the interface between the skin and the coated web.

In contrast, the composition according to the invention, comprising both phosphate and acrylic functions, makes it possible to obtain a good quality of adhesion, whatever the monomer concentration, as evidenced by the complete exfoliation of the treated tissue.

It was therefore observed that, at equivalent concentrations and with similar chemical structure, the presence of phosphate functions in the polymerizable monomers used in the composition according to the invention makes it possible to increase the resistance to cracking and to ensure cohesion (i.e. strength of adhesion) by penetration into the surface layer of the tissue to be treated.