WO2003086327A2 - Radical polymerisation activator for the production of coloured non-toxic organic cements - Google Patents

Abstract

The invention relates to a method for production of a polymeric material or a polymeric cement, which is coloured, obtained by polymerisation of an acrylic or methacrylic monomer in the presence of a peroxide type hardener and at least one decomposition activator of the tertiary amine type of formula (I), where R3 is an resonant electron-donating group which generates the colouration of the polymer or the cement during the polymerisation reaction and R1 and R2 are alkyl, arylalkyl or alkyidene groups. The invention further relates to a polymerisable composition and a preparation kit for an acrylic or methacrylic coloured cement and acrylic or methacrylic coloured cements particularly useful in the medical field as bone cement.

Description

Radical polymerization activator for obtaining colored and non-toxic organic cements

The present invention relates to the field of radical polymerization of acrylic or methacrylic monomers and relates more particularly to the preparation of colored polymers as well as non-toxic colored polymer cements, in particular usable in the medical field, without using conventional pigments.

A field of application envisaged is in particular that of bone cements or dental cements but also that of cements used in vertebroplasty, for which the toxicity of the available compounds is a brake on the use of some of them which nevertheless have properties sealing and mechanical properties compatible with this application.

The applications of the invention are not however limited to the medical field. They also extend to all areas where colored cements are sought, in particular for example that of building.

Known bone cements are usually obtained by mixing on the one hand a solid phase generally consisting of poly (methyl methacrylate) or a copolymer based on methyl methacrylate in powder form and an organic initiator of the peroxide type. , and on the other hand a liquid phase comprising at least one monomer, for example methyl methacrylate and an activator of the decomposition of said organic initiator. Thus, the solid and liquid phases are capable of being stored separately from each other and it is only when they are mixed during the production of the cement that the activator plays its role and accelerates decomposition. peroxide, which forms free radicals capable of reacting with the monomers to induce the propagation of the polymerization reaction of the monomer. Obviously, the polymerization time, which is considerably reduced thanks to the presence of the activator, must remain long enough for the practitioner to mix and then seal the prosthetic device in the bone material. In this way the polymerization of methacrylate forms a matrix in which are trapped the particles of polymethacrylate and other components such as in particular, a radio-opacifier and sometimes an antibiotic; the assembly constituting a solid possibly trapping the prosthetic elements and adhering to the internal and / or external bone walls. STATE OF THE ART

The peroxide decomposition accelerator, hereinafter called activator, is usually dimethylparatoluidine (DMPT), a tertiary aromatic amine. This molecule is very toxic to humans and its small size -131g / mol- suggests that it can migrate into cement (US3,740,850) then into bone and end up being harmful for the carrier of the prosthesis over time.

Several patents have been filed in an attempt to replace this activator with a less toxic molecule. For example, the inventors of US Pat. No. 4,284,551, filed in 1981, show that the para-aminophenylethanol derivatives (DMAPE) can be good candidates for the activation of benzoyl peroxide (BPO) at room temperature. The reactivity of these derivatives depends very little on the size of the substituents carried by the nitrogen atom (methyl group in the case of DMAPE), but it very much depends on the substituent in para of the benzenic cycle. In the derivatives proposed in this patent, the substituent is of acetoxy type, which leads to an activation of the decomposition of BPO less than DMAPE (alcohol substituent), itself less than that of DMPT. According to the authors, a polymer-type support does not bring any additional interest. The bone cements usually used also have another drawback: the polymerization reaction of methyl methacrylate is exothermic and due to the confinement of the reaction medium, the polymerization self-accelerates, an effect known as the Tromsdorff effect. This leads to a rise in temperature in the cement placed, up to 90 ° C in some cases, while the proteins of the human body coagulate from 60 ° C. The necrosis caused could be avoided if the polymerization used was less exothermic. US Pat. No. 4,782,118 (1988) suggests adding an oligomer carrying glycidyl methacrylate functions in the solid phase and methylanilylglycidyl methacrylate as activator in the liquid phase. The oligomer is introduced to store part of the heat energy released by the polymerization of methyl methacrylate after activation of BPO (benzoyl peroxide). The activator, after having played its role with BPO, can also participate in the polymerization via its reactive end. The glycidyl functions provided by the oligomer post-crosslink the cement thereafter.

The international application WO95 / 30480 describes the use of tertiary amines of high molecular weight to store the heat energy released by the radical polymerization and to avoid the migration of the amine then into the cement. Several tertiary pluriamines have been proposed, most with an acetoxy group in para of the benzenic nucleus or with a long spacer between tertiary aromatic amines. Certain amines carry a reactive double bond or are supported by a polymer of 2000 to 5000 g / mol, always with an acetoxy group in para of the benzenic nucleus. The results show that the polymerization kinetics in the presence of this latter activator is slower than in the case of DMPT, but the exotherm is much less significant. This phenomenon had already been described in patent EP0383595 where particles of crosslinked polymer were incorporated into the phase solid to dissipate the heat energy released during polymerization in the presence of DMPT.

More recently, tertiary amines less toxic than DMPT, according to the authors, have been described. Three tertiary amines (N, N-dimethyl-4-toluidine (DMPT), N, N-dimethylbenzyl alcohol (DMOH) and N, N- dimethylbenzyl methacrylate (DMMO)) were compared in terms of their toxicity and their potency d activation of BPO (Vazquez, B., Levenfeld, B., San Roman, X, Polym. Int. 1998, 4t _ \), 241-250). Amines derived from dimethylbenzyl appear to have no mutagenic or cytotoxic effects, unlike DMPT; in addition, the maximum temperature reached when setting the cement is lower, which presents the tissues, especially with DMMO. The disadvantage is that the setting time increases, especially since the maximum temperature reached is low. Another activator was proposed in 1999 by the same authors: it is 4-N, N-dimethylaminobenzyl laurate (DML) (1 Biomed. Mater. Res. 1999, 48 (5), 719-725) . According to the authors, this activator is even less toxic than the previous ones and makes it possible to obtain satisfactory mechanical properties, with a reduced maximum temperature reached, but a longer setting time.

Thus, various attempts have been made to date, in particular to reduce the toxicity of cements and the exothermic nature of the polymerization reactions implemented.

Furthermore, the setting of the cement in the presence of tertiary amines, generally used such as dimethylparatoluidine (DMPT) or dimethylaminophenylethanol, is accompanied by a slight yellow coloration of the material obtained. Thus, when the cement has definitively set, it is difficult to distinguish it from the bone, so that any attempt to loosen it by means of a cutter without damaging the bone part is made delicate. The present invention proposes to remedy all the problems not resolved by the prior art and for this purpose proposes the use of an activator for decomposition of the radical initiator which, not only, is not liable to migrate in cement and which makes it possible to attenuate the thermal energy produced by the polymerization reaction, but also and above all which is not likely to lead to the formation of a cement having a color similar to that of bone.

More precisely, the invention relates, according to a first essential characteristic, to a process for the preparation of a polymer, in particular a colored polymer cement, based on an acrylic or methacrylic monomer, said process being carried out by presence of a radical polymerization initiator of the peroxide type and of a decomposition activator of said radical polymerization initiator of the tertiary amine type, characterized in that said decomposition activator of said radical polymerization initiator comprises a tertiary amine corresponding to the formula (I):

dans laquelle :

in which :

the group R3 is an electron-donor group by resonance comprising at least one aromatic group which is capable of forming with the radical:

et en combinaison avec ledit amorceur de polymérisation radicalaire, un système conjugué présentant une absorption dans le domaine visible du spectre électromagnétique, pour générer la coloration dudit polymère ou dudit ciment au cours de la réaction de polymérisation dudit monomère, - les groupements RI et R2 sont respectivement et indépendamment : • des groupes alkyle en Cl à C16, de préférence en Cl à C5, linéaires ou ramifiés,

and in combination with said radical polymerization initiator, a conjugated system exhibiting absorption in the visible range of electromagnetic spectrum, to generate the coloring of said polymer or of said cement during the polymerization reaction of said monomer, - the groups RI and R2 are respectively and independently: • C1 to C16, preferably C1 to C5 alkyl groups, linear or branched,

• C5 to C30, preferably C5 to C10 aryl or arylalkyl groups,

• C2 to C15 alkylidene groups, preferably C2 to C5.

By way of simplification, these amines of formula (I) will be designated below by activator of the invention.

According to a second essential characteristic, the invention relates to a polymerizable composition containing at least one acrylic or methacrylic monomer and at least one activator for decomposition of a radical polymerization initiator of the peroxide type, in which at least one activator meets the definition given above.

According to a third essential characteristic, the invention relates to an assembly for preparing a colored acrylic or methacrylic cement, in particular a bone, dental cement or a cement intended for use in vertebroplasty or else a cement intended for be used in building, comprising on the one hand a pulverulent product and a radical initiator of the peroxide type, and on the other hand a polymerizable composition as defined above.

Finally, according to its last characteristic, the invention relates to colored acrylic or methacrylic cements obtained by implementing the process which is the subject of the first characteristic of the invention, by mixing a polymerizable composition as defined above. above with a radical polymerization initiator of the peroxide type and a pulverulent product. As previously stated, the invention relates to the preparation of acrylic or methacrylic polymers, in particular colored or non-toxic acrylic or methacrylic cements.

It particularly relates to non-toxic colored cements having setting times and a maximum setting temperature during their preparation compatible with use in the medical field.

By polymer or colored cement within the meaning of the invention is meant that the final product has a color distinctly different from that of the bone, this color resulting from the particular choice which is made according to the present invention from group R3 which must be a resonant electron-donor group comprising at least one aromatic group which is capable of forming with the radical:

et en combinaison avec ledit amorceur de polymérisation radicalaire, un système conjugué présentant une absorption dans le domaine visible du spectre électromagnétique.

and in combination with said radical polymerization initiator, a conjugated system having absorption in the visible range of the electromagnetic spectrum.

The molar mass of the activators of the invention is greater than that of dimethylparatoluidine so that they present less risk of migration in the cement and in the organism and are therefore less toxic. In addition, these tertiary amines give the mixture of monomers and radical initiator polymerization reaction rates similar to those obtained by dimethylparatoluidine without the overall temperature of the mixture reaching the same maximum values.

Furthermore, the tertiary amine of formula (I) in which R3 is an electron donor group by resonance favorably activates the decomposition of the radical initiator. It will easily be understood that the presence of at least one aromatic group in the group R3 allows coloring during polymerization and contributes to increasing the mass of the amine.

Furthermore, the activation will be better when the R3 groups include at least one tertiary amine linked to at least one of these aromatic groups.

Thus, the preferred activators for the implementation of the process of the invention as well as for the other objects of the invention will be products of the tertiary polyamine type in which the various tertiary amine groups are carried by aromatic groups.

As soon as the activator and the radical initiator are in contact with each other and the initiation phase of the reaction is in progress, the assembly becomes colored and this coloration persists after the reaction has ended. In this way, as will be explained in more detail in the following description, this characteristic allows the surgeon on the one hand to be able to distinguish that the polymerization has indeed taken place and on the other hand to distinguish the product from a support whitish in color like bone. Furthermore, the aromatic group tends to increase the reactivity of tertiary nitrogen and therefore the kinetics of the initiation phase and consequently the overall speed of the polymerization reaction.

According to a variant of the invention, the activator of formula (I) is a tertiary diamine of formula (I) in which the group R3 is of the form:

où :

or :

- X 'is chosen from: CH ₂ , O, OC ₆ H ₄ -O, NH, NR and

- R8, R9 and R are respectively and independently:

Linear or branched C1 to C16, preferably C1 to C5 alkyl groups, • C5 to C30, preferably C5 to C10 aryl or arylalkyl groups,

• C2 to C15 alkylidene groups, preferably C2 to C5. Another interesting diamine for implementing the invention in its various aspects is N, N, N ', N' tetramethylbenzidine (TMB).

According to other variants of the invention, the R3 group comprises at least two tertiary amines carried by two different aromatic rings.

Thus, according to a variant of the invention, the group R3 is a group of the form:

dans lequel : - X est choisi parmi : CH, N, et

in which: - X is chosen from: CH, N, and

- R4, R5, R6 and R7 are chosen from:

• linear or branched C1 to C16, preferably C1 to C5 alkyl groups,

• C5 to C30, preferably C5 to C10 aryl or arylalkyl groups,

• C2 to C15 alkylidene groups, preferably C2 to C5. A particularly advantageous activator according to this embodiment is:

HC CH ₃ This tertiary triamine which is 4, 4 ′, 4 "-methylidynetris (N, N- dimethylaniline), commonly designated by" crystal-violet leuco "or more simply" leuco "is particularly interesting as an activator, account given the symmetry of the molecule and the presence of three possible active sites to activate the radical polymerization initiator.

According to another particularly advantageous embodiment, a tertiary amine of formula (I) is used in which R3 is a group of form:

- XI and X2 being chosen from: N and CH, - RIO to R15 being independently:

Linear or branched C1 to C16, preferably C1 to C5 alkyl groups,

• C5 to C30, preferably C5 to C10 aryl or arylalkyl groups, • C2 to C15, preferably C2 to alkylidene groups

C5.

Thus, the various products of formula (I) used as activator according to the process of the present invention, not only increase the molar mass of the tertiary amines which are the subject of the invention, which makes them less mobile and therefore less toxic than DMPT but also provide the desired coloring effect. Furthermore, the aromatic group R3 forms with the tertiary amine of formula (I) and in combination with the radical initiator a conjugated system capable of absorbing visible light from the electromagnetic spectrum. Obviously, the resulting color will depend on the wavelengths of the spectrum absorbed by the conjugate system.

According to a particularly preferred variant of the process of the invention, the activator responsible for coloring the polymer or the final cement is used in the presence of at least one other activator for decomposition of the radical polymerization initiator of tertiary amine type, said additional activator, in particular with the aim of reducing the toxicity which the second activator could confer alone or to reduce the maximum temperature reached during the polymerization, while benefiting from the property of the activators of the invention of imparting a coloration clean with polymers and cements obtained according to the process of the invention.

It is also possible to use as additional activator at least one activator from the family of activators of formula (I), with the aim of modifying the coloration obtained.

The proportions of the activator (or activators) according to the invention and of the other activators may vary within very wide ranges, the quantity of activator according to the invention being however sufficient to impart a clear coloring to the polymer or to the cement. during and after the polymerization of the monomer.

Thus, DMPT is widely used today and its formulation in cement is something well known to those skilled in the art. It appeared to the inventors of the present invention that by replacing at least a few percent of DMPT with the molar equivalent of a tertiary amine of formula (I) according to the invention, the coloration of the polymer product, in particular of cement, while retaining the same setting kinetics and equivalent mechanical properties. In fact, the amines do not activate the breakdown of peroxide at exactly the same speed and by mixing several, the setting speed of the cement can be adjusted, with the disadvantage that this requires a new development phase. It is therefore understandable that it can be very advantageous to obtain a clear coloring without having to considerably change the conditions of the polymerization process.

The same is true for dimethylaminophenylethanol which, too, is currently used as an activator for decomposition of peroxides but which, too, like DMPT can be used in combination in wide ranges of proportions with the tertiary amines of formula (I ) used according to the invention with the same advantages.

Thus, according to a particularly advantageous variant of the process, the amine used according to the invention corresponding to formula (I) will be used in combination with DMPT or dimethylaminophenylethanol, or with one of their mixtures, the proportions of the different types of activator can vary within very large proportions, the proportion of tertiary amine of family (I) remaining, however, greater than or equal to 5 mol% relative to all the activators to ensure the desired coloring function. Finally, other associations prove to be particularly useful for implementing the process of the invention and, in particular all associations with tertiary amines of the amino polymer type which make it possible to considerably reduce the maximum temperature reached during polymerization. , which allows for medical applications, to preserve the tissues.

Thus, according to another variant, it turns out to be particularly advantageous to use the tertiary amine of formula (I) according to the invention in combination with a polymer corresponding to one of the two formulas (II) and (III) ci below:

in which :

- 0.1 <x <0.9 and 0.9> y> 0.1, with x + y = 1,

- n is between 5 and 1000,

- R16 and R17 are independently:

Linear or branched C1 to C16, preferably C1 to C5 alkyl groups,

• C5 to C30, preferably C5 to C10 aryl or arylalkyl groups,

• C2 to C15 alkylidene groups, preferably C2 to C5. or :

(III)

in which

- n is between 2 and 1000,

- R18 and R19 and R'3 are respectively and independently:

Linear or branched C1 to C16, preferably C1 to C5 alkyl groups,

• C5 to C30, preferably C5 to C10 aryl or arylalkyl groups, • C2 to C15 alkylidene groups, preferably C2 to C15

C5. These polymers can be obtained by amination of a poly (styrene-co-bromostyrene) copolymer itself obtained by bromination of a polystyrene according to a process inspired by those described in the publications of Camps M., Montheard JP, Bonrokia F. , Camps JM, Pham QT, Eur. Polym. 1, 26 (1), 53 (1990) and Heaney H., Chem. Rev., 62, 81 (1962))

Thus, the polymer of formula (II) is a tertiary amine having a large molar mass so that it does not risk migrating into a solid phase constituted by bone cement, but also the skeleton of the chain of this polymer is inductive. donor on the benzenic nucleus comprising the tertiary amine so that the reactivity of tertiary nitrogen is increased. In the case of activator associations according to the invention with other activators, the coloring of the polymer products is more or less sustained, depending on the amount of colored amine introduced: for example with leuco, the cement turns pale blue intense purple if a DMPT / leuco mixture corresponding to 99 / l% by mass to 0/100% is used. In the case of TMB, the coloration is less intense, it is perceptible from DMPT / TMB = 90/10%.

In addition, DMPT, which is the most widely used amine today, is inherently toxic and, due to its size, it can migrate in cement over time. By mixing it with a less toxic amine, the toxicity of the entire cement is reduced.

The use of amines TMB, leuco causes a high temperature when setting the cement; by using it in admixture with the amino polymer of formula II or III, the maximum temperature reached is reduced, which preserves the tissues. In addition, the use of several activators of formula (I) makes it possible to modulate the final coloration of the product. In general, the radical polymerization initiator is a peroxide of the benzoyl peroxide type. Thus, the tertiary nitrogen of the activator can act directly on an oxygen of the peroxide to initially form a first radical comprising a free electron on the other oxygen which is terminal and which is capable of acting on the monomer for start the polymerization reaction. Now tertiary nitrogen is capable of acting as oxygen directly on the carbon to form radicals.

According to its second object, the present invention provides a polymerizable composition containing at least one acrylic or methacrylic monomer and an activator for the decomposition of a radical polymerization initiator of the peroxide type in which said activator comprises a product corresponding to formula (I) in all the variants described above. According to a particularly advantageous variant of this second aspect, this activator is used in combination with a second decomposition activator of the radical polymerization initiator as also described above.

The polymerizable composition forms a single stable liquid phase which can be stored and conditioned in this form and whose monomer can only react in the presence of a radical initiator which will be activated by the activator of the invention contained in the liquid phase. In this way, the polymerizable composition containing the activator according to the invention is capable of being mixed with a solid phase containing a polymer in powder form and a radical initiator to form a cement having all the characteristics set out above; that is to say, a cement whose activator, said tertiary amine, does not migrate, whose temperature is lower than that which is reached with the activators of the prior art and whose color is distinct from the color of the bone material, all of these characteristics being combined without reducing the mechanical characteristics of the hardened cement.

Yet another object of the present invention relates to an assembly for preparing a colored acrylic or methacrylic cement, in particular a bone, dental cement or a cement intended for use in vertebroplasty or else a cement intended to be used in building, comprising on the one hand a pulverulent product and a radical initiator of the peroxide type, and on the other hand a polymerizable composition as defined in any one of the claims as defined above.

The assembly initially comprises two phases isolated from each other in two separate containers, a first solid phase containing the pulverulent product and the radical initiator, and a phase, hereinafter called the monomer phase, containing the monomer and l activator capable of activating the decomposition of the radical initiator. It is only at the time of use that the operator mixes the two phases of methyl methacrylate, to prepare the cement and that he applies it, for example, to seal any prosthesis in a bone or dental cavity. . As soon as the monomer phase is intimately mixed with the solid phase, the decomposition of the radical initiator by the activator takes place and this priming step makes it possible to provide free radicals. The latter are capable of reacting on the monomer so that, in a propagation step, the polymerization takes place. The overall speed of the polymerization process and therefore of hardening or setting of the cement, after the phases have been mixed, is obviously compatible with the time necessary for the implementation and installation of a prosthetic device.

According to a preferred embodiment of the invention, the pulverulent product is based on polymers and copolymers based on methyl methacrylate, of small particle size and said radical initiator is a peroxide, for example benzoyl peroxide (BPO) . The colored cements of the invention find, due to their reduced toxicity and the moderate nature of the exothermicity of the polymerization reaction, numerous applications in the medical field, and very particularly as bone cement, dental cement or in the field of vertebroplasty.

Of course, their composition and very particularly the mass compositions of the solid phase and of the monomer phase of the cement as well as the proportions of these two phases depend on the field of application. Thus, with regard to bone cements, depending on the viscosity desired by the surgeon for implementation, the proportion of solid phase (PMMA powder) relative to the monomer phase (MMA) results in the manufacture of a cement to high viscosity or low viscosity.

In general, the mass composition of the solid phase is as follows: approximately 90% of powder of polymers and copolymers based on MMA, 1% of BPO (radical initiator) and 9% of radio-opacifier (oxide of zirconium or barium sulfate).

The mass composition of the monomer phase is advantageously 98% of methacrylic monomers. The proportion of monomer phase relative to the solid phase is generally 30 to 40% (or approximately 70% of solid phase in the whole cement).

As explained above, the advantage of coloring cement in the medical field is, on the one hand, to assure the surgeon that polymerization runs smoothly and, on the other hand, to be able to clearly distinguish cement from bone or dental material, which greatly facilitates a number of operations for the practitioner, especially during a recovery intervention.

In the dental field where the coloring of a definitive cement is not sought, use will be made essentially of the cement of the invention for temporary repairs or the pause of temporary prostheses intended to be replaced quickly.

As previously explained, the colored cements of the invention also find particularly interesting applications in the building industry, in particular for sealing elements.

EXAMPLES

Example 1

Colored cements prepared using the product called "leuco crystal violet" as an activator (4,4, '4 "-methylidynetris (N, N- dimethylaniline))

Use is made, as activator of the decomposition of the radical initiator, of a tertiary amine of formula:

que l'on mélange tout d'abord avec le monomère pour former la phase liquide.

which is first mixed with the monomer to form the liquid phase.

The monomer consists of a mixture of two monomers, methyl methacrylate (MMA) and butyl methacrylate (BuMA).

The solid phase consists of polymethyl methacrylate (PMMA) particles in powder form, the particle size of which is essentially between 20 and 130 μm and preferably between 50 and

80 μm. In addition, it contains a radical initiator, benzoyl peroxide (BPO) and zirconium oxide ZrO ₂ as a radio-opacifier. The percentages by weight of the different elements of the two phases mixed together are given in the table below:

The cement obtained by the homogeneous mixture of the two phases and therefore of the respective constituents of the two phases, exhibits a blue-violet color which persists after hardening. This is one of the advantages of the invention, since the bone cement is then distinguished from the bone which is whitish, and can be removed, from the bone wall, in a later stage, by means of a cutter for example, without risk of damaging said bone wall. In addition, the hardening of the cement is obtained after approximately 10 minutes, just like the cements formulated with activators of the prior art. at. Leuco-based cement setting kinetics

Cement temperature (° C) during setting of the cement

The setting times are the same when they are made under the same initial temperature conditions; depending on the tests, the setting time can vary by almost a minute and the temperature reached depends on where the probe is planted in the cement. b. Mechanical properties

The mechanical properties of the cement thus obtained are comparable to those of the cements obtained according to the same formulation in which the activator of the decomposition of the radical polymerization initiator is dimethylparatoluidine (DMPT) usually used in the prior art. The table below presents comparative values of the mechanical properties of the two cements obtained according to iso 5833 standard:

vs. Leuco-based cement cytotoxicity measurements

The cytotoxicity test was carried out in direct contact with the bone cement, according to ISO 10993-5 and EN 30993-5:

The test in direct contact on the bone cement made from the product prepared in the presence of DMPT leads to the conclusion of cytotoxicity of the product (value of 2 corresponding to a loss of 20 to 39% of cell density compared to the negative test, on a scale of 0 to 5, on which the value 5 corresponds to more than 80% of cell density), while bone cement made from leuco crystal violet is not.

In conclusion, although the results relating to the maximum stress under load (or average resistance to compression) are lower by approximately 10 MPa, for the cement produced with the activator leuco crystal-violet, the other parameters have comparable values , and this new activator is perfectly acceptable. In addition, unlike the cements obtained with DMPT, it is not toxic since the activator molecule does not migrate into the cement and its blue-violet color gives it the above-mentioned advantages.

Example 2:

Cement prepared using N, N, N ', N'-tetramethylbenzidine (TMB) as an activator

The results are given below in comparison with those obtained with DMPT for cements obtained from the solid and liquid phases defined below:

- Composition of the solid phase: 41.7g PMMA (homogeneous particle size (50-80μm)), 0.5g of BPO, 4.3g ZrO2,

- Composition of the liquid phase: 16.6g MMA, 2.54g BuMA, 0.393g of DMPT (2.9xl0 ^"3 mol) or 0.35g of TMB (1.45xl0 ^{" 3} mol).

Cement temperature (° C) during setting of the cement

Les temps de prise sont les mêmes quand ils sont faits dans les mêmes conditions de température initiale.

The setting times are the same when they are made under the same initial temperature conditions.

The test specimens are produced and tested in compression according to ISO5833 standard. The results are as follows:

The cement obtained with TMB is non-toxic, brown / yellow in color, however, the mechanical results are less interesting than the previous cement.

Example 3:

Colored cement obtained in the presence of an activator consisting of a mixture of a colored amine according to the invention and of DMPT or of polystyrene amino

Different cements are prepared from a solid phase and a liquid phase, the proportions and composition of which are given below:

- Composition of the solid phase: 23.9g PMMA / BPO / ZrO2 (89.8 / 1.0 / 9.2% by mass),

- Composition of the liquid phase: 7.9g MMA, 1.2g BuMA, and the amine (see table below).

In this example, the effect of DMPT alone is compared with that of various associations according to the invention:

- DMPT + TMB,

- DMPT + leuco, - leuco + polystyrene functionalized at 50% with dimethylamine (15,000 g / mol and 7.97 × 10 ³ of amino function per gram of product in solid form). This polymer is prepared by bromination of a polystyrene in a process analogous to those described in the publications of Camps M., Montheard JP, Bonrokia F., Camps JM,

Pham Q.T., Eur. Polym. J., 26 (1), 53 (1990) and Heaney H., Chem. Rev., 62, 81 (1962))

The table below gives in its last column, the maximum load stress values for each of the polymers obtained.

The test pieces are produced and tested according to ISO5833 standard. The results are as follows:

It is observed during the tests carried out that it suffices to replace a few percent of conventional amine (DMPT) with one of the colored amines to obtain the coloring of the whole cement (blue in the case of leuco and green then brown in the case of TMB).

The mechanical properties obtained change according to the mixtures produced: leuco does not modify the mechanical properties of conventional cement (and it decreases its toxicity), while TMB and amine PS give cements with a mechanical resistance slightly lower than that of conventional cement , but achieves a setting temperature lower than the usual temperature. Example 4: Kit for preparing a bone or dental cement

The kit comprises a first container in which is housed a pulverulent product based on polymethyl methacrylate and benzoyl peroxide as initiator of radical polymerization; and in a second containing a polymerizable composition consisting of methyl methacrylate as monomer and as activator of decomposition of a radical initiator a tertiary amine of formula:

The two containers of the preparation kit are capable of being stored and marketed together, without the polymerizable composition being able to react; it is only after having thoroughly mixed the contents of the two containers together, that the cement thus formulated can be applied in a bone cavity to seal a prosthesis. The polymerization reaction obviously begins when said tertiary amine has activated the benzoyl peroxide which itself initiated the reaction. However, the formulation of the compounds used is such that the cement gradually hardens so that the operator can proceed with the fitting of a prosthesis and filling the bone cavity with said cement in pasty form.

Claims

1. A process for the preparation of a polymeric material, in particular a colored polymer cement, based on an acrylic or methacrylic monomer, said process being carried out in the presence of a radical polymerization initiator of the peroxide type and of a decomposition activator of said radical polymerization initiator of tertiary amine type, characterized in that said decomposition activator of said radical polymerization initiator comprises a tertiary amine corresponding to formula (I):

in which : the group R3 is an electron-donor group by resonance comprising at least one aromatic group which is capable of forming with the radical:

and in combination with said radical polymerization initiator, a conjugated system having absorption in the visible range of the electromagnetic spectrum, for generating the coloration of said polymer or of said cement during the polymerization reaction of said monomer, - the groups RI and R2 are respectively and independently: Linear or branched C1 to C16, preferably C1 to C5 alkyl groups, • C5 to C30, preferably C5 to C10 aryl or arylalkyl groups, • C2 to C15 alkylidene groups, preferably C2 to C5. 2. Method according to claim 1, characterized in that said group R3 comprises at least one tertiary amine linked to an aromatic group. 3. Method according to one of claims 1 or 2, characterized in that the group R3 is a group of the form:

in which : - X is chosen from: CH, N, and - R4, R5, R6 and R7 are chosen from: • linear or branched C1 to C16, preferably C1 to C5 alkyl groups, • C5 to C30, preferably C5 to C10 aryl or arylalkyl groups, • C2 to C15 alkylidene groups, preferably C2 to C5. 4. Method according to one of claims 1 to 3, characterized in that said activator corresponds to the formula:

5. Method according to one of claims 1 or 2, characterized in that the group R3 is of the form:

or : - X 'is chosen from: CH ₂ , O, OC ₆ H ₄ -0, NH, NR and - R8, R9 and R are respectively and independently: • linear or branched C1 to C16, preferably C1 to C5 alkyl groups, • C5 to C30 aryl or arylalkyl groups, preferably C5 to CIO, • C2 to C15 alkylidene groups, preferably C2 to C5. 6. Method according to one of claims 1 or 2, characterized in that said activator is N, N, N ', N' tetramethylbenzidine. 7. Method according to one of claims 1 or 2, characterized in that the group R3 is a group of the form:

XI and X2 being chosen from: N and CH, RIO to R15 being independently: • C1 to C16, preferably C1 to C5 alkyl groups, linear or branched, • C5 to C30, preferably C5 to C10 aryl or arylalkyl groups, • C2 to C15 alkylidene groups, preferably C2 to C5. 8. Method according to one of claims 1 to 7, characterized in that said radical polymerization initiator is benzoyl peroxide. 9. Method according to one of claims 1 to 8, characterized in that it is implemented in the presence of at least one other activator for decomposition of the radical polymerization initiator, called additional activator, belonging or not to the family of activators of formula (I), said activator (s) corresponding to formula (I) being in an amount effective for imparting the coloration of said polymeric material or of said cement. 10. Method according to claim 9, characterized in that it is implemented in the presence of at least one additional activator chosen from the group consisting of dimethylparatoluidine, dimethylaminophenylethanol and their mixtures. 11. Method according to one of claims 9 or 10, characterized in that it is implemented in the presence of an additional activator corresponding to one of the two formulas (II) and (III) below:

in which: - 0.1 <x <0.9 and 0.9> y> 0.1, with x + y = 1, - n is between 5 and 1000, - R16 and R17 are independently: Linear or branched C1 to C16, preferably C1 to C5 alkyl groups, • C5 to C30, preferably C5 to C10 aryl or arylalkyl groups, • C2 to C15 alkylidene groups, preferably C2 to C5. or :

(III) in which - n is between 2 and 1000, - R'3, R18 and R19 are respectively and independently: Linear or branched C1 to C16, preferably C1 to C5 alkyl groups, • C5 to C30, preferably C5 to C10 aryl or arylalkyl groups, • C2 to C15 alkylidene groups, preferably C2 to C5. 12. Polymerizable composition containing at least one acrylic or methacrylic monomer and at least one activator for the decomposition of a radical polymerization initiator of the peroxide type, characterized in that it contains at least one activator of the tertiary amine type corresponding to the formula ( I):

ï vnii • wu '"S" • " ^β 30 as defined in one of claims 1 to 7. 13. A polymerizable composition according to claim 12, characterized in that said group R3 comprises at least one tertiary amine linked to an aromatic group. 14. Polymerizable composition according to one of claims 12 or 13, characterized in that the group R3 is a group of the form:

as defined in claim 3. 15. Polymerizable composition according to one of claims 12 to 14, characterized in that said activator corresponds to the formula:

16. A polymerizable composition according to claim 12 or 13, characterized in that the group R3 is of the form:

as defined in claim 5. 17. Polymerizable composition according to one of claims 12 or 13, characterized in that said activator is N, N, N ', N' tetramethylbenzidine. 18. Polymerizable composition according to one of claims 12 or 13, characterized in that the group R3 is a group of the form:

as defined in claim 7. 19. Polymerizable composition according to one of claims 12 to 18, characterized in that it contains at least one other activator for decomposition of the radical polymerization initiator said additional activator, belonging or not to the family of activators of formula ( I), said activator (s) corresponding to formula (I) being in an amount effective for imparting the coloration of said polymeric material or of said cement. 20. A polymerizable composition according to claim 19, characterized in that it contains at least one additional activator chosen from the group consisting of dimethylparatoluidine, dimethylaminophenylethanol and their mixtures. 21. Polymerizable composition according to one of claims 18 to 20, characterized in that it contains at least one additional activator corresponding to one of the two formulas (II) or (III) below, as defined in the claim 10.

(II)

(M) 22. Kit for preparing a colored acrylic or methacrylic cement, in particular a bone, dental cement or a cement intended for use in vertebroplasty or else a cement intended for use in building, comprising on the one hand a pulverulent product and a radical initiator of the peroxide type, and on the other hand a polymerizable composition as defined in any one of claims 12 to 21. 23. An assembly for preparing a colored acrylic or methacrylic cement according to claim 22, characterized in that said pulverulent product is based on a polymer or a copolymer of methyl methacrylate. 24. An assembly for preparing an acrylic or methacrylic cement colored according to one of claims 22 or 23, characterized in that said radical initiator is benzoyl peroxide. 25. Colorful acrylic or methacrylic cement, in particular bone, dental cement or cement intended for use in vertebroplasty or else cement intended for use in building, characterized in that it is obtained by mixing a polymerizable composition according to a of claims 12 to 21 with a radical polymerization initiator of the peroxide type and a pulverulent product, in particular a pulverulent product based on a polymer or a copolymer of methyl methacrylate and / or one of its copolymers.