WO2011080573A2

WO2011080573A2 - Endodontic cement with high bioactivity

Info

Publication number: WO2011080573A2
Application number: PCT/IB2010/003355
Authority: WO
Inventors: Carlo Prati; Maria Giovanna Gandolfi
Original assignee: Alma Mater Studiorum - Universita' Di Bologna
Priority date: 2009-12-29
Filing date: 2010-12-29
Publication date: 2011-07-07
Also published as: WO2011080573A3; IT1397051B1; ITBO20090835A1

Abstract

A composition for endodontic use, in particular for retrograde root fillings or side perforations, the composition comprises from 40% to 85% by weight, with respect to the total weight of the composition, of particles of Portland cement and from 10% to 45% by weight, with respect to the total weight of the composition, of a partially hydrophilic methacrylic polymerizable resin.

Description

ENDODONTIC CEMENT WITH A HIGH BIOACTIVITY

TECHNICAL FIELD

The present invention relates to a composition and to uses of such a composition.

BACKGROUND OF THE INVENTION

Endodontic cements are a class of materials with a broad clinical application and bound to have an ever increasing use considering both the high number of patients with endodontic diseases in old age and the development of conservative therapy. Endodontic cements are introduced in root canals and are in contact with the dentine of the tooth element and with the periapical bone tissue, i.e. they have at least two contact surfaces, one inside the tooth and one outside and in contact with the bone tissue. Such materials must have as ideal properties a good biological integration, a good biocompatibility and osteoconductive properties, i.e. they must allow a normal bone turnover and also create a microenvironment allowing to promote the healing of the adjacent and surrounding tissue.

Such cements must have the property of being easy to introduce in the deep cavity of the dentine (thus of the tooth) obtained after removal of the infected and degenerate dentinal tissue. Furthermore, such cements must be easy to introduce into the surgical site and in the area lacking tissue. They must also have a good formability, suitable hardening times, good mechanical properties and must harden in damp environments contaminated by saliva, blood and derivatives.

Currently, very few materials available on the market have some (and never all) of these properties.

Nowadays available endodontic cements are zinc oxide/eugenol cements with or without the addition of polymers of the epoxy resin type (AH plus) , glass- ionomeric cements and calcium hydroxide cements . None of these cements have osteoconductive properties or the ability to harden in damp environments and all degrade in the course of time.

The patent application with publication number US2008/0318190 includes a generic disclosure of compositions indicating different possible components which are alternative to one another, but (apart from a single specific example) gives no indication of the quantitative ratios among some of these components.

The only specific example of US2008/0318190 (see in particular table 6) relates to a composition containing 45 % by weight of Portland cement and more than 40% by weight (in particular 43%) by weight of a resin (formulation VI of table 1) .

The patent application with publication number US2008/0045678 includes a generic disclosure of compositions indicating different possible components which are alternative to one another, but (apart from a few specific examples) gives no indication of the quantitative ratios between some of these components. It should in any case be noted that the amount of cement component is preferably lower than 50% by weight (last three lines of paragraph [0021]).

The few specific examples of US2002/0045678 relate to compositions having components of more than 5% by weight only inorganic components (for example Portland cement) and polymers (for example PPG - polypropylene glycol and PEG polyethylene glycol) .

Recently some mineral calcium-silicate cements derived from Portland cement have been developed for endodontic use such as Pro-Root MTA (Dentsply^®, Germany) , MTA-Angelus (Angelus Dental Solutions^®, condrina, Brazil) and Aureoseal (Ogna^®, Italy) .

The main drawbacks of mineral cements which are currently on the market are: excessively long hardening times, solubility and scouring by biological fluids, poor formability and complicated preparation, difficult introduction in the surgical site.

Pro-Root MTA, which contains bismuth oxide (Bi₂03) introduced to obtain radiopacity, displays for example a long hardening time (2 hours and 45 minutes) that leads to its scouring from the surgical site when it is reached by the blood/plasma flow. Furthermore, its resistance to compression (40 MPa) increases slowly in the course of time reaching a maximum value of only 67 MPa after 21 days and this does not allow its use in areas subjected to high functional loads.

Currently, biomaterials that are directed to an endodontic use and are applicable both in contact with the external bone tissue and with the bone tissue adjacent to the tooth element and that are bioactive and have short enough hardening times are not available on the market .

SUMMARY

It is an object of the present invention to provide a composition and uses of such a composition, which allow to overcome at least partially the drawbacks of the state of the art and are at the same time easy and cost-effective to implement.

According to the present invention, there are provided a composition and uses of such a composition according to the following independent claims and, preferably, according to any of the claims directly or indirectly dependent on the independent claims .

Unless otherwise explicitly specified, the following terms have the following meaning.

In the present text, C_X-C_Y is referred to a group that is intended to have from x to y carbon atoms.

In the present text, by aliphatic there is intended a non aromatic and non substituted, saturated or unsaturated, linear, branched and/or cyclic hydrocarbon. Non-limitative examples of aliphatic groups are: t- butyl, ethenyl, ethyl, 1- or 2-propenyl, n-propyl, 2- propyl, cycloesyl, cycloesenyl.

In the present text, by alkyl there is intended a saturated aliphatic (i.e. an aliphatic group having no double or triple carbon-carbon bonds) . Non-limitative examples of alkyls are: methyl, ethyl, n-propyl, t- butyl , cycloesyl .

In the present text, by alkenyl there is intended an aliphatic having a double carbon-carbon bond.

In the present text, by hydroxy-aliphatic there is intended an aliphatic group bound to at least one hydroxy group (-OH) .

In the present text, by hydroxy-alkyl there is intended an alkyl group bound to at least one hydroxy group (-OH) .

In the present text, by carboxy-aliphatic there is intended an aliphatic group bound to at least one carboxyl group (-COOH) .

In the present text, by carboxy-alkyl there is intended an alkyl group bound to at least one carboxy group (-COOH) .

In the present text, by ether there is intended two aliphatics bound to one another by an oxygen. Advantageously, by ether there is intended two alkyls bound by an oxygen. Non-limitative examples of ethers are: -CH₂-0-CH₃, -C₂H₄-0-CH₃, -CH₂-0-CH₂-, -C₂H₄-0-C₂H₄- .

In the present text, by diether there is intended three aliphatics arranged in series and in which one of the aliphatics is connected to the other two by an oxygen. Advantageously, by diether there is intended three alkyls arranged in series and in which one of the alkyls is bound to the other two by an oxygen. Non- limitative examples of diethers are: -CH₂-O-CH₂-O-CH₃ , - C2H4-O-C2H₄-CH₃, -CH₂-O-CH2-O-CH₂-, -C₂H₄-O-C2H₄-O-C₂H4-.

Unless explicitly indicated otherwise, the content of the references (papers, texts, patent applications etc.) cited in this text is herein incorporated by way of completeness of description. In particular, the above mentioned references are herein incorporated by reference .

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will now be described with reference to the accompanying drawings, which illustrate some non-limitative embodiments thereof, in which:

- figure 1 shows the release of calcium ions by some compositions according to the present invention and by some compositions of the state of the art; the measurements after 3 hours, 24 hours, 7 days, 14 days, 28 days are indicated on the X axis; the calcium released in ppm is indicated on the Y axis;

- figure 2 shows IR spectra of a composition of the state of the art; the wavenumber (cm^-1) is indicated on the X axis, the transmittance is indicated on the Y axis;

figure 3 shows IR spectra of a composition according to the present invention; the wavenumber (cm^" ¹) is indicated on the X axis, the transmittance is indicated on the Y axis;

- figure 4 shows Ramam spectra of a composition according to the present invention; the wavenumber (cm^" ¹) is indicated on the X axis, the Raman intensity is indicated on the Y axis;

- figure 5 shows Ramam spectra of a composition according to the state of the art; the wavenumber (cm^-1) is indicated on the X axis, the Raman intensity is indicated on the Y axis;

- figure 6 shows the trend of the ratio of the Raman intensity 1964/1855 as a function of the ageing time of a composition according to the present invention and a composition according to the state of the art; the data relate to 1 (on the left) and 14 (on the right) days ;

- figure 7 is an ESEM/EDX image of a composition according to the present invention used to fill a retrograde cavity;

- figure 8 is an EDX spectrum of the composition of figure 7 ;

- figure 9 is an ESEM/EDX image of a composition according to the present invention used to fill a retrograde cavity;

- figure 10 is an EDX spectrum of the composition of figure 9;

- figures 11 and 12 are two ESEM/EDX images of the composition of figure 7 after 24 hours of immersion in DPBS ;

- figure 13 is an EDX spectrum of the composition of figure 11;

- figures 14 and 15 are two ESEM/EDX images of the composition of figure 9 after 24 hours of immersion in DPBS; and

- figure 16 is an EDX spectrum of the composition of figure 13.

EMBODIMENTS OF THE INVENTION

According to a first aspect of the present invention, there is provided a composition comprising from 40% to 85% by weight, with respect to the total weight of the composition, of particles of mineral calcium-silicate material and from 10% to 45% by weight, with respect to the total weight of the composition, of a polymerisable resin.

Advantageously, the sum of the weights of the mineral calcium-silicate material and of the polymerisable resin is higher or equal to 90% of the overall weight of the composition.

According to some embodiments, the composition comprises up to 80% by weight, with respect to the total weight of the composition, of the particles of a mineral calcium-silicate material. According to some embodiments, the composition comprises at least 50% (advantageously, at least 60%) by weight, with respect to the total weight of the composition, of the particles of a mineral calcium-silicate material.

According to some embodiments, the composition comprises up to 30% (advantageously, up to 25%) by weight, with respect to the total weight of the composition, of the polymerisable resin. According to some embodiments, the composition comprises at least 15% (advantageously, at least 20%) by weight, with respect to the total weight of the composition, of the polymerisable resin.

Advantageously, the percentage by weight, with respect to the total weight of the composition, of the particles of the mineral calcium-silicate material is higher than the percentage by weight, with respect to the total weight of the composition, of the polymerisable resin.

The mineral calcium-silicate material comprises at least 30% (advantageously at least 35%) by weight, with respect to the weight of the mineral calcium-silicate material, of a sum of tricalcium silicate and dicalcium silicate.

Usually, the tricalcium silicate is identified by formula 3(CaO)-Si0₂. Usually, the dicalcium silicate is identified by formula 2(CaO)-Si0₂.

Advantageously, the mineral calcium-silicate material comprises at least 40% (in particular, at least 45%) by weight, with respect to the weight of mineral calcium-silicate material, of the sum of tricalcium silicate and dicalcium silicate.

According to some embodiments, the mineral calcium- silicate material comprises at least 40% (in particular, at least 45%) by weight, with respect to the weight of the mineral calcium-silicate material, of tricalcium silicate. According to some embodiments, the mineral calcium-silicate material comprises up to 75% (in particular, up to 50%) by weight, with respect to the weight of the mineral calcium-silicate material, of tricalcium silicate.

According to some embodiments, the mineral calcium- silicate material comprises at least 7% (in particular, at least 20%) by weight, with respect to the weight of the mineral calcium-silicate material, of dicalcium silicate. According to some embodiments, the mineral calcium-silicate material comprises up to 35% (in particular, up to 30%) by weight, with respect to the weight of the mineral calcium-silicate material, of dicalcium silicate.

According to some embodiments, the mineral calcium- silicate material comprises tricalcium aluminate. In particular, the mineral calcium-silicate material comprises at least 2% (advantageously, at least 5%) by weight, with respect to the weight of the mineral calcium-silicate material, of tricalcium aluminate. According to some embodiments, the mineral calcium- silicate material comprises up to 15% (in particular, up to 13%) by weight, with respect to the weight of the mineral calcium-silicate material, of tricalcium aluminate.

Usually, the tricalcium aluminate is identified by formula 3 (CaO) ·Al₂0₃.

According to some embodiments, the mineral calcium- silicate material comprises tetracalcium aluminoferrite. In particular, the mineral calcium-silicate material comprises at least 2% (advantageously, at least 5%) by weight, with respect to the weight of the mineral calcium-silicate material, of tetracalcium aluminoferrite. According to some embodiments, the mineral calcium-silicate material comprises up to 18% (in particular, up to 10%) by weight, with respect to the weight of the mineral calcium-silicate material, of tetracalcium aluminoferrite.

Usually, the tetracalcium aluminoferrite is identified by formula 4(CaO) ·Α1₂0₃ -Fe20₃.

According to some embodiments, the mineral calcium- silicate material comprises anhydrous and/or hemihydrate and/or hydrated calcium sulphate. In particular, the mineral calcium-silicate material comprises at least 1% (advantageously, at least 2%) by weight, with respect to the weight of the mineral calcium-silicate material, of (anhydrous and/or hemihydrate and/or hydrated) calcium sulphate. According to some embodiments, the mineral calcium-silicate material comprises up to 10% (in particular, up to 5%) by weight, with respect to the weight of the mineral calcium-silicate material, of (anhydrous and/or hemihydrate and/or hydrated) calcium sulphate.

Usually, (anhydrous and/or hemihydrate and/or hydrated) calcium sulphate is identified as gypsum.

According to some embodiments, the mineral calcium- silicate material is selected from the group consisting of: Portland cement and clinker of Portland cement.

Portland cement is a commonly used kind of cement . It is usually marketed as powder obtained by the milling of clinker of Portland cement.

According to some embodiments, Portland cement is defined by the ASTM C150 classification or by the EN- 197.1; these two classifications are not completely overlapping .

Advantageously, with reference to the object of the present text, Portland cement is in accordance with the EN-197.1 regulation. In particular, Portland cement belongs to class I of the EN-197.1 regulation.

By mineral calcium-silicate material particles there is intended particles having an average diameter smaller than 0.2 mm (advantageously, smaller than 80 μπι) . Advantageously, the particles have a mean diameter greater than 0.01 pm.

According to different embodiments, the mineral calcium-silicate material particles may have different size.

According to some embodiments, the particles of mineral calcium-silicate material have a mean diameter from 0.5 μπι to 80 μκι. According to alternative embodiments, the particles of mineral calcium-silicate material have a mean diameter from 0.01 |im to 0.5 |im.

Unless otherwise specified explicitly, in the present text, the diameter of the particles is measured by means of a scanning electronic microscope (SEM) . In particular, a SEM (SEM-EDX 515 Philips Eindhoven) connected to an energy dispersive X ray spectrometer (EDS) (Inca, Oxford Instruments, UK) is used. The mean diameter is calculated by computing the mean of the measuring of the diameter of 100 randomly selected particles .

Advantageously, the polymerisable resin is a photopolymerisable resin.

The polymerisable resin comprises 5% by weight, with respect to the weight of the polymerisable resin, of a polymerisable organic monomer.

Advantageously, the polymerisable resin comprises at least 20% (in particular, at least 30%) by weight, with respect to the weight of the resin, of the organic monomer. According to some embodiments, the polymerisable resin comprises up to 80% (in particular, up to 75%) by weight, with respect to the weight of the resin, of the organic monomer. According to some specific embodiments, the polymerisable resin comprises at least 35% (in particular, at least 50%) by weight, with respect to the weight of the resin, of the organic monomer. According to some specific embodiments, the polymerisable resin comprises up to 70% by weight, with respect to the weight of the resin, of the organic monomer .

Advantageously, the organic monomer has a partition coefficient (LogP) lower or equal to 1.2. In particular, the organic monomer has a partition coefficient (LogP) lower or equal to 1.0. According to some embodiments, the organic monomer has a partition coefficient (LogP) lower than 0.6 (advantageously, lower or equal to 0.5).

Advantageously, the organic monomer has a partition coefficient (LogP) higher than -1.0. According to some embodiments, the organic monomer has a partition coefficient (LogP) higher than -0.5 (in particular, higher than 0.0). According to specific embodiments, the organic monomer has a partition coefficient (LogP) higher or equal to 0.20.

In the present text "LogP" indicates the logarithm to base ten of the ratio of partition octanol/water of a specific compound (i.e. the ratio between the concentration of a solute in octanol and in water) . Advantageously, the LogP (partition coefficient) is defined and computed according to what is disclosed within the article "Structure-toxic ty relationship of acrylates and methacrylates" ; H Tanii, K Hashimoto ; TOXICOLOGY LETTERS 1982; 11 ( 1-2 ): 125-129 ; ICID: 472084; PMID 7090003.

Advantageously, the organic monomer is amphiphilic. According to some embodiments, the organic monomer has at least one vinyl group, which reacts during polymerisation. Advantageously, the organic monomer comprises at least one group selected from the group consisting of: hydroxy (-OH) , carboxy (-COOH) , sulphuric (-S0₄H), sulphurous (-S0₃H) , aminic (for example, -NH₃) .

It should be noted that the carboxy, sulphate and sulphonate groups tend to deprotonate in a substantially- neutral aqueous solution. It should be noted that the aminic group tends to protonate in a substantially neutral aqueous solution.

Advantageously, the organic monomer comprises a hydroxy group (-OH) .

According to some embodiments, the organic monomer comprises at least 5 carbon atoms .

According to some embodiments, the organic monomer is an ester of an acid selected from the group consisting of: acrylic acid, methacrylic acid. According to specific embodiments, the organic monomer is an ester of methacrylic acid.

According to some embodiments, the organic monomer has the following structure:

CH₂=C(R³)COO-R²

wherein R² is selected from the group consisting of: carboxy-Ci-C4-aliphatic, hydroxy-Ci-C4-aliphatic . Advantageously, the hydroxy group is bound to the second carbon with respect to the oxygen bound to R². According to some embodiments, R² is a hydroxy-aliphatic group, more in particular hydroxyl-alkyl . Advantageously, R² is a C1-C3 group. According to specific embodiments, R² is CH₂CH₂OH .

According to specific embodiments, R³ is selected from the group consisting of: -H, Ci-C4 aliphatic. In particular, R³ is selected from the group consisting of: -H, Ci-C4 alkyl. According to some embodiments, R³ is selected from the group consisting of: -H, C₁-C2 aliphatic. In particular, R³ is selected from the group consisting of: -H, C₁-C₂ alkyl . According to some embodiments, R³ is selected from the group consisting of: -H, -CH₃. According to specific embodiments, R³ is - CH₃.

According to specific embodiments, the organic monomer is acrylic acid or methacrylic acid. According to some embodiments, the polymerisable resin comprises, as well as the organic monomer, acrylic acid. According to some embodiments, the polymerisable resin comprises from 1% to 30% (in particular, about 15%) by weight, with respect to the weight of the composition, of acrylic acid.

According to some embodiments, the organic monomer is selected from the group consisting of: HEMA (2- hydroxyethyl methacrylate) , HPMA ( 3-hydroxypropyl methacrylate) , PE TA (dipentaerythritol penta acrylate monophosphate) , 4-META (4-methacryloxyethyl trimellitate anhydride) . According to some embodiments, the organic monomer is selected from the group consisting of: HEMA (2-hydroxyethyl methacrylate) , HPMA (2-hydroxypropyl methacrylate) .

HEMA has the following structure:

CH₂=C(CH₃)COO-CH₂CH₂OH

According to specific embodiments, the organic monomer is HEMA.

Advantageously, the polymerisable resin has a molar fraction of at least 0.1 (in particular, at least 0.2) of a cross-linking agent adapted to react with the organic monomer during the polymerisation of the organic monomer. According to some embodiments, the polymerisable resin has a molar fraction lower than 0.53 (advantageously, lower than 0.44) of the crosslinking agent. In particular, the organic monomer and the crosslinking agent are different.

According to some embodiments, the polymerisable resin has a molar fraction of at least 0.23 (advantageously, at least 0.27) of a cross-linking agent adapted to react with the organic monomer during the polymerisation of the organic monomer. According to some embodiments, the polymerisable resin has a molar fraction lower than 0.40 (advantageously, lower than 0.34) of the crosslinking agent.

In the present text, unless otherwise specified, by molar fraction there is intended the molar fraction with respect to the polymerisable resin.

Advantageously, the polymerisable resin comprises at least 20% (in particular, at least 30%) by weight, with respect to the weight of the polymerisable resin, of the crosslinking agent. According to some embodiments, the polymerisable resin comprises up to 90% (advantageously, up to 70%) by weight, with respect to the weight of the polymerisable resin, of the crosslinking agent.

According to some embodiments, the polymerisable resin comprises at least 40% (in particular, at least 45%) by weight, with respect to the weight of the polymerisable resin, of the crosslinking agent. According to some embodiments, the polymerisable resin comprises up to 60% (advantageously, up to 55%) by weight, with respect to the weight of the polymerisable resin, of the crosslinking agent.

Advantageously, the crosslinking agent is a crosslinking monomer adapted to react with the organic monomer during the polymerisation of the organic monomer.

According to some embodiments, the crosslinking monomer has a partition coefficient (LogP) higher than 1. In particular, the crosslinking monomer has a partition coefficient (LogP) higher than 2.

Advantageously, the crosslinking monomer has at least two vinyl moieties. According to specific embodiments, the crosslinking monomer has three vinyl groups. According to specific embodiments, the crosslinking monomer has two vinyl groups.

Advantageously, the crosslinking monomer is an ester of an acid selected from the group consisting of: acrylic acid, methacrylic acid. In particular, the crosslinking monomer is an ester of methacrylic acid.

Advantageously, the crosslinking monomer comprises in its structure at least two esters of methacrylic acid. According to specific embodiments, the crosslinking monomer comprises in its structure two esters of methacrylic acid.

According to specific embodiments, the crosslinking monomer has the following structure:

CH₂=C (R⁴) COO-R^OOC (R⁵) C=CH₂

wherein R¹ is selected from the group consisting of: alkyl, alkenyl , ether, diether. According to some embodiments, R¹ is selected from the group consisting of: Ci-Cio alkyl, Ci-Ci₀ alkenyl, C₂-C₈ ether, C₃-C₈ diether. According to some embodiments, R¹ is selected from the group consisting of: alkyl, ether, diether. According to some embodiments, R¹ is selected from the group consisting of: alkyl, ether, diether. According to some embodiments, R¹ is selected from the group consisting of: ether, diether. According to some embodiments, R¹ is a diether.

According to some embodiments, where R¹ is an alkyl, R¹ is Ci-Cs , in particular C₂-C8, more in particular C₃-C₆. According to some embodiments, where R¹ is an alkenyl, R¹ is Ci-Cs , in particular C2-C₈ , more in particular C₃-C6. According to some embodiments, where R¹ is an ether, R¹ is C₂-C₇, in particular C₃-C₈, more in particular C₃-C₇. According to some embodiments, where R¹ is a diether, R¹ is C₃-C₇, in particular C₃-C₆, more in particular C₆.

According to some embodiments, where R¹ is a diether, R¹ is:

-R⁶-0-R⁷-0-R⁸- wherein R⁶, R⁷ and R⁸ are, independently of each other, C1-C3 alkyl .

According to specific embodiments, R⁴ and R⁵ are selected, independently of each other, from the group consisting of: H, C1-C4 aliphatic. In particular, R⁴ and R⁵ are selected, independently of each other, from the group consisting of: H, Ci-C4-alkyl. According to some embodiments, R⁴ and R⁵ are selected, independently of each other, from the group consisting of: H, C1 -C2 aliphatic. In particular, R⁴ and R⁵ are selected, independently of each other, from the group consisting of: H, Ci-C2-alkyl. According to some embodiments, R⁴ and R⁵ are selected one independent of the other from the group consisting of: -H, -CH₃. Advantageously, R⁴ and R⁵ are identical. According to specific embodiments, R⁴ and R⁵ are each a respective -CH₃.

According to specific embodiments, the crosslinking monomer is TEGMA (triethylene glycol methacrylate) .

TEGMA has the following formula:

CH₂=C(CH₃)COO-CH2-CH2-0-CH2-CH2-0-CH2-CH₂OOC (CH₃)C=CH₂ Specifically, structure:

According to some embodiments, the polymerisable resin comprises at least 20% by weight, with respect to the weight of the resin, of a substantially hydrophobic monomer adapted to react with the organic monomer, during the polymerisation of the organic monomer. In particular, the substantially hydrophobic monomer has a partition coefficient (LogP) higher than 1. According to some variants, the substantially hydrophobic monomer has a partition coefficient (LogP) higher than 2. According to some embodiments, the substantially hydrophobic monomer corresponds to the crosslinking monomer.

Advantageously, the resin comprises an initiator, in particular a photoinitiator . According to some embodiments, the composition comprises from 0.01% to 5% (advantageously, from 0.01% to 3%) by weight, with respect to the total weight of the composition, of the initiator .

According to some embodiments, the photo-initiator is selected from the group consisting of: camphoroquinone, phenylpropanedione, lucrin TPO, DMPA (dimethoxy-phenylacetophenone) . In particular, the photo-initiator is selected from the group consisting of: camphoroquinone, phenylpropanedione, DMPA

(dimethoxy-phenylacetophenone) . According to specific embodiments, the photo-initiator is camphoroquinone (CQ) .

Advantageously, the resin comprises a co-activator. According to some embodiments, the composition comprises from 0.01% to 15% (advantageously, from 0.01% to 2%) by weight, with respect to the total weight of the composition, of the co-activator.

According to some embodiments, the co-activator is selected from the group consisting of: EDMAB (ethyl 4- (dimethylamino)benzoate) , N,N-dimethyl-p-toluidine, DMAEM (di-methyl amino ethyl methacrylate) . According to specific embodiments, the co-activator is selected from the group consisting of: EDMAB (ethyl 4- (dimethylamino)benzoate) , N,N-dimethyl-p-toluidine. According to specific embodiments, the co-activator is EDMAB.

According to some embodiments, the composition comprises a polymer of acrylic acid (PAA) . In particular, the composition comprises up to 30% (more in particular up to 15%) by weight, with respect to the weight of the composition, of the polymer of acrylic acid. According to specific embodiments, the polymer of acrylic acid has a molecular weight from 2000 to 150000 dalton.

According to some embodiments, the composition comprises a radiopaque agent. In particular, the composition comprises from 10% to 30% by weight, with respect to the weight of the composition, of radiopaque agent .

According to some embodiments, the radiopaque agent is selected from the group consisting of: BaS0₄, ZnO, Ti0₂, Zr0₂, ZnO, CaW0₄, Bi₂0₂ (C0₃). Advantageously, the radiopaque agent is BaS0₄. BaS0₄ allows the passage of light through the composition therefore promoting the photopolymerisation reaction.

According to specific embodiments, the composition consists of the mineral calcium-silicate material and of the polymerisable resin. According to variants, the composition consists of the mineral calcium-silicate material, of the radiopaque agent and of the polymerisable resin.

According to specific embodiments, the resin consists of the organic monomer, the crosslinking monomer and of the initiator. According to variants, the resin consists of the organic monomer, the crosslinking monomer, the co-activator and the initiator. According to variants, the resin consists of the organic monomer, the crosslinking monomer, the substantially hydrophobic monomer, the co-activator and the initiator.

According to some aspects of the present invention there is provided a composition that differs from the above defined composition only in that instead of the polymerisable resin it comprises a polymer which is already polymerised or partially polymerised.

This polymer is obtained by polymerising the mentioned resin.

The composition according to the present invention has experimentally shown the following technical advantages with respect to the state of the art:

no scouring by biological fluids in virtue of the fast hardening following the polymerisation of the resin;

- easy preparation and use;

bioactivity, i.e. the formation of a bone-like apatite layer, i.e. a substituted carbonate apatite, in the presence of fluids (solutions, in particular aqueous solutions) containing phosphate (saliva and/or blood) in virtue of the release of calcium ions (note that apatite is substantially formed by calcium phosphate) ;

suitable and improved biocompatibility with respect to the biomaterials used for the same clinical applications ;

exposure of a hydrophilic surface suitable to absorb serum proteins and the following cellular/osteoblastic colonisation;

- activation of the osteoblasts by calcium and silicium;

activation of the nucleation of apatite by calcium and silicium.

In connection to the above, the surprising properties of the composition of the present invention are due to unexpected synergic actions of the different components . After having analysed the properties of the material, the following has been suggested.

The particles of mineral calcium-silicate material in the presence of water perform/are subjected to a hydration reaction that consists of the hydrolytic degradation of the surface of the calcium-silicate minerals with formation on the surface of a layer formed by hydration products (mainly CSH calcium-silicate gel, ettringite and soluble calcium hydroxide) that slows down the diffusion of the water (penetration of the ions through this film) and therefore the progress of the hydration reaction. The calcium-silicate gel exposes Si- OH groups for binding the dentinal apatite and for nucleating apatite crystals. The dissolution of calcium hydroxide releases calcium ions that diffuse through the matrix of the polymer obtained by the resin and are expelled by the material following an osmotic gradient.

It should be noted that the presence of the organic monomer, which is at least partially hydrophilic, does not prevent the hydration of the mineral material therefore allowing the release of portlandite or calcium hydroxide. Furthermore, in virtue of the partial absorption of water (swelling) by the organic monomer, the volume reduction (shrinkage) due to the polymerisation of the resin is at least partially compensated.

Therefore, the bond between cement and root dentine

(and therefore the ability to seal the root canal) is enhanced by the hydrophilicity of the organic monomer.

Furthermore, when the organic monomer is appropriately selected, the organic monomer tends to interact with the mineral phases (self-adhesion to mineral phase) and in particular with the mineral component of the tooth tissues (apatite) and with the calcium ions released during the hydration of the mineral calcium-silicate material, in particular by chelation [Zainuddin et al, J Mater Sci Mater Med 2006] .

Therefore, the bond between cement and root dentine (and therefore the ability to seal the root canal) is further improved when the organic monomer is selected appropriately as shown above.

The nucleation of the apatite is also further enhanced by the presence of silicates. In particular, the Si-OH groups exposed by the calcium-silicate minerals and by the CSH calcium-silicate gel formed by hydration form sites for binding calcium ions of the dental apatite and sites for the nucleation of apatite crystals .

In use, the polymerisable resin (in particular, HEMA and TEGMA) seems to create a polymer network capable of stabilising the outer surface of the cement and a hydrophilic matrix sufficiently permeable to absorb water. The heterogeneous nucleation of the apatite seems to take place in nucleation sites (SiO/Si- OH groups from CSH groups and containing oxygen from poly-HEMA-TEGMA) by absorbing calcium and phosphate ions . The groups containing oxygen of the polymerised resin (poly-HEMA-TEGMA) provide additional nucleation sites through the formation of calcium chelates.

The combination of the mineral calcium-silicate material and of the polymerised resin creates the conditions (release of calcium and functional moieties capable of chelating calcium ions) to obtain a bioactive composition that hardens fast.

The formation of a bioactive coating on the surface of the cement and the short hardening times represent properties which are extremely interesting for a material used in dental and maxillofacial surgery. The composition according to the present invention therefore has the fundamental chemical-physical properties useful for use in the field of intra-root cavities and bone.

The composition according to the present invention is suitable for use in retrograde endodontic surgery at the apex of the tooth element, i.e. in the case of apicoectomy (root end resection) and in the case of root perforation repair.

Therefore, according to further aspects of the present invention the following is provided.

A composition as disclosed above, for use in dentistry.

A composition as disclosed above, for endodontic use.

A composition as disclosed above, to perform retrograde root fillings or fillings of side or furcation perforations .

A use of a composition as disclosed above, for the preparation of a product for dental use in mammals (in particular in humans) .

A use of a composition as disclosed above, for the preparation of a product for endodontic use in mammals (in particular in humans) .

A use of a composition as disclosed above, for the preparation of a product for use in retrograde root fillings or side perforation in mammals (in particular in humans) . Further features of the present invention will result from the following disclosure of some embodiments given by mere way of non-limitative illustration.

Example 1

Preparation of the resin

HEMA, TEGMA; EDMAB and CQ were mixed together until the powders were totally dissolved. The mixture obtained thereby was stored in a dark container (i.e. a container that does not allow light to pass through) in a refrigerator (+8°C) .

Prepared resins

By using the above disclosed method, resins having the following compositions were prepared:

1 ) HEMA 46.6 mL (=50 grams the density being = 1.073 g/ml)

TEGMA 45.8 mL (=50 grams the density being = 1.092 g/ml)

EDMAB 0.924 grams (1% by weight, with respect to the total weight of the resin)

CQ 0.231 grams (0.25% by weight, with respect to the total weight of the resin)

2) HEMA 60 grams

TEGMA 40 grams

EDMAB 0.924 grams (1% by weight)

CQ 0.231 grams (0.25% by weight)

3) HEMA 70 grams

TEGMA 30 grams

EDMAB 0.924 grams (1% by weight) CQ 0.231 grams (0.25% by weight)

4 ) HEMA 50 grams

TEGMA 50 grams

EDMAB 1 grams

CQ 0.3 grams

5) HEMA 60 grams

TEGMA 40 grams

EDMAB 1.3 grams

CQ 0.5 grams

6) HEMA 3.8 grams

TEGMA 3.8 grams

EDMAB 0.76 grams

CQ 0.19 grams

7) HEMA 48.9% by weight (50 grams) + UDMA-PEG 48.9% (50 grams) + CQ 0.4% (0.37 grams) + EDMAB 0.8% (0.86 grams)

Example 2

Preparation of the cement-resin composition

A gram of mineral powder, which contains 0.8 grams of Portland cement CEM I (Aalborg Denmark) and 0.2 grams of barium sulphate, was mixed with 273 μΐ (corresponding to about 0.308 g) of resin.

Prepared composition

A) mineral powder + resin of example 1.1; in this case the composition comprised Portland cement 63.84%, barium sulphate 15.69%, HEMA 9.98%, TEGMA 9.98%, EDMAB

0.18%, CQ 0.025% (these percentages are by weight and referred to the overall weight of the composition) . B) mineral powder + resin of example 1.2

C) mineral powder + resin of example 1.3

D) mineral powder + resin of example 1.4

E) mineral powder + resin of example 1.5

F) mineral powder + resin of example 1.6

Example 3

The compositions of example 2 are subjected to light radiation in the spectrum of blue for a time of about 120 seconds. Almost immediately after having been subjected to light radiation, all the compositions were quite hard and capable of overcoming the test for the initial setting time as disclosed in example 5.

Example 4

A composition was prepared by mixing 0.55 g Portland cement with barium sulphate (8:2) with 0.150 ml of resin on a glass plate (composition A of example 2) . The composition obtained thereby was placed in a non metallic mould having a diameter of 0.8 mm and a height of 1-6 ± 1mm, and polymerised (3M curing light 2500) after having been applied on the surface of a transparent matrix (Directa Matrix Strips, Directa AB, Upplands Vasby, Sweden) . The mould was then rotated upside down and the transparent matrix was applied again. The lower surface was also polymerised. Finally the sample was gently removed from the mould.

Example 5

Setting Time

The test was performed according to the specifications of the International Organization of Standard (ISO) 9917-1:2007. The setting time was determined with the use of two Gilmore needles, the lighter needle (113.4 g) having a diameter of 2 mm for the initial setting, the heavier needle (453.6 g) having a diameter of 1 mm for the final setting time. Both needles were positioned gently on the surface of the sample for 5 seconds. The material was considered hardened when the needle leaves no indentation on the surface of the sample.

The setting time was evaluated on the samples immediately after photopolymerisation and/or exposure to halogen light (table 1) to evaluate the loss of consistence in the presence of fluid. The samples were obtained by using the procedure disclosed in example 4. The final setting times were measured subjecting the samples to photopolymerisation and following immersion in water.

The tests were repeated three times and the mean of the results is indicated in the following table 1. The times indicated in table 1 include the polymerisation times (for example composition A which was photopolymerised for 60 seconds showed a final setting time after 569 minutes) .

Table 1

Materials P (s) Initial Setting Final Setting Time (min) Time (min)

120 2 2

Composition A 90 1.5 390

60 1 570

120 2 2

Composition B 90 1.5 480

120 2 480

Composition C 90 1.5 300

ProRoot MTA® 55 78

wTC-Ba _ 55 105 wTC-Ba contains 80% Portland cement CEM I (Aalborg Denmark) and 20% barium sulphate.

It should be noted that even when the polymerisation time is relatively short as not to allow the complete polymerisation of the resin, a sort of protective film that reduces the possibility that part of the material is scoured (washed away) is created in any case on the surface of the composition. When the polymerisation time is relatively short, the presence of this protective film appears to slow down the final setting time; nevertheless, it should be noted that it has been experimentally observed that the protective film has often shown to ensure protection before reaching the final time setting.

Example 6

Radiopacity The test was performed according to the specifications of the International Organization of Standard (ISO) 9917-1:2007. The samples were positioned on an X-Ray sheet of the D type having a size of 30 x 40 mm, commonly used for intra-oral X rays. Three samples were arranged on the left side of each sheet, while a 98% pure aluminium wedge with a step increasing by a 1 mm-6 mm step was arranged on the right side. The tooth radiogenic unit was oriented at a distance of about 3 cm from the sheet. The exposure time was set to 0.13 seconds. All the sheets were developed by means of an automatic developing machine. The X rays were acquired by means of an optical scanner (Epson perfection V750Pro) and computer analysed by means of an image analysis software "Image j" (Rasband, W.S., ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, USA, 1997-2008. Abramoff, M.D., Magelhaes, P.J., Ram, S.J. "Image Processing with ImageJ" .Biophotonics International, volume 11, issue 7, pp. 36-42, 2004) . The shades of grey both of the aluminium wedge and of the samples were measured for each sheet. The shades of grey of the aluminium plate were inputted in a linear equation system that correlates the shade of gray to the thickness in millimetres of aluminium (Al mm) . The means of the shades of grey were finally inputted in the linear system thereby obtaining the radiopacity of the cement in equivalent Aluminium millimetres .

The results of the different tests which were carried out are shown in table 2.

Table 2

In table 2 and in the other examples: wTC indicates a powder of Portland cement CEM I (Aalborg Denmark; wTC- Ba indicates a mineral powder having the composition of the mineral powder of example 2 ; the resin has the composition of the resin of example 1.1; ProRoot MTA® and Vitrebond® are commercially available products; wTC- Bi indicates a mineral powder having a composition similar to the mineral powder of example 2 in which an identical amount of bismuth oxide is present instead of barium sulphate; n indicates the number of tests which are performed, the values shown in the right column is the mean thereof .

Example 7 Solubility

Each sample was weighed by using an analytical scale with a precision of 0.0001 g, repeating each weighing three times . Each sample was therefore immersed in a sealed container (40 mm diameter and 30 mm height) containing 5.07 ± 1 mL of medium and placed in an incubator at a temperature of 37 °C.

After the previously set immersion time, each sample was removed from the container and rinsed on both larger surfaces with 2 ml of medium (using a pipette loaded with 0.5 ml and repeating the operation 4 times). The sample was dried at a temperature of 37°C for 24 hours and finally weighed with the precision of 0.0001 g performing 3 weightings for each sample. The mean of the weighting was computed.

The variation of percentage mass (V%) , i.e. the mass variation following immersion, was finally obtained with an accuracy of 0.1% according to the formula:

V% = [(final mass - initial mass) / initial mass] x 100

Two different immersion means were used: double distilled water, as requested by the ISO regulation, and DMEM with 10% FBS, to reproduce the possible behaviour of the material in contact with biological fluids. The immersion times which were analysed were 1, 14 and 28 days .

The samples were obtained by using the procedure disclosed in example 4. The tests performed after immersion in 5 ml of H₂0 were repeated 5 times and the means of the results is indicated in the following table 3.

Table 3

The tests of table 3 were repeated replacing water with DMEM (Dulbecco/Vogt modified Eagle's minimal essential medium) +FBS (Fetal bovine serum) in a ratio of 10:1. The results are shown in table 4.

Table 4

in DMEM+FBS V% after 1 day V¾ after 14 V% after 28 days days

Composition A - 3.64 ± 1.51 + 6.25 ± 2.91 + 6.67 ± 1.36

Composition B - 5.04 ± 1.64 - 0.08 + 4.77 + 6.38 ± 4.45

Composition C - 10.57 ± 1.01 - 3.44 ± 4 + 5.93 ± 2.87

Vitrebond® - 9.44 ± 0.44 - 4.19 ± 0.43 - 3.3 + 0.23 wTC-Ba -11.52 ± 1.22 -5.22 ± 3.48 + 3.94 ± 3.26 In tables 3 and 4: Vitrebond® is a commercially available product; the loss of weight is indicated by -; the increase in weight is indicated by + .

Example 8

Each sample was immersed in a sealed container (40 mm diameter and 30 mm height) with 5 ± 1 ml of double distilled water and placed in an incubator at a temperature of 37 °C.

Measurements of the pH and the concentration of calcium ions were carried out (to identify the extent of the release) after predetermined time intervals.

At the end of each measurement, the water in which the samples were immersed was replaced with pure distilled water.

The pH of the solution was measured with Ionolab

WTW, immersing the probe in the water by at least 2 cm. The pH was measured after 1, 14 and 28 days.

The release of calcium ions was measured similarly using Ionolab WTW.

The samples were obtained by using the procedure disclosed in example 4.

The pH values obtained by different measurements are shown in table 5a.

Table 5a

pH in H]0 3 hours 1 day 7 days 14 days 28 days

Composition A 10.6 ± 0.1 11.7 + 0.2 10.5 ± 1.0 9.6 ± 1.0 9.8 ± 0.7 Composition B 10.4 ± 0.4 11.8 ± 0.2 10.7 ± 1.0 10.1 ± 0.6 9.4 ± 0.3

Composition C 11.1 ± 0.0 11.8 ± 0.1 11.7 ± 0.1 10.4 ± 0.4 9.9 ± 0.6

Vitrebond® 11.5 ± 0.2 11.4 ± 0.0 10.8 ± 0.6 9.3 ± 0.5 9.2 ± 0.7 wTC-Ba 5.9 ± 0.1 6.0 ± 0.1 7.0 ± 0.2 6.7 ± 0.1 6.4 ± 0.4

Water 6.88 ±0.44 7.00 ±0.02 7.10 ±011 6.63 ±0.11 6.95 ±0.09

The release values (concentration ppm with respect to distilled water) of the calcium obtained for different measurements are shown in table 5b.

Table 5b

Figure 1 shows the overall release of calcium ions in water.

The curve with the detections indicated by symbol ♦ relates to Composition A; the curve with the detections indicated by symbol ■ relates to Composition B; the curve with the detections indicated by symbol A relates to Composition C; the curve with the detections indicated by symbol * relates to wTC-Ba. Example 9

Evaluation study of the marginal seal with ESEM/EDX

In the present study, the cements were used to fill retrograde cavities in vitro, simulating a retrograde surgical intervention (apicoectomy) . Thereby, the degree of marginal adaption and sealing of cements was evaluated and it was also possible to evaluate their bioactivity. Permanent maxillary incisor with a completely formed apex and a single root canal were selected from a group of tooth elements extracted from adults. The teeth were extracted for surgical reasons and stored in distilled water at a temperature of 4°C for longer than one month.

The coronal portion of each tooth was removed at the CEJ using a diamond saw so as to obtain a working length of 14 ± 1 mm.

All roots were machined with the Crown-down technique using K-files (Dentsply Maillefer, Ballagues, CH) so that #30 sized apexes were obtained. The roots were finally profiled with NiTi tools (Protaper, DentSply, USA) mounted on a low speed micromotor (X- Smart, Dental Sply, USA) .

After each machining the sample was washed with 1 ml of 5.25% NaOCl (Ogna, Maggio, Italia) followed by 0.5 itiL of 10% EDTA (Ogna, Maggio, Italia) , using a 27-gauge needle syringe (Molteni, Firenza, Italia) .

All roots were finally filled with a single gutta percha cone (Hygenic, USA) and the 3 apical mm were removed from each root with the use of a diamond reamer mounted on a turbine. The retrograde preparation was finally performed with a diamond ultrasound tip (ProUltra Surgical; Dentsply Maillefer) mounted on a Piezosteril 5 endodontic handpiece (Castellini, Castelmaggiore, Italia) . The depth of each cavity was determined by the length of the working part of the reamer (3.0 mm). The cements (composition A and wTC-Ba - as defined in example 12) were applied directly in the cavity using a steel spatula. In particular, composition A was immediately photoplymerised for 90 seconds with a halogen light lamp, while the wTC-Ba was simply applied in the cavity. Half of the samples were immediately evaluated with ESEM /EDX without metallisation. The other half of the samples was immersed in a DPBS solution (simulated body fluid solution) and maintained at a temperature of 37 °C for 24 hours and then, finally, analysed by ESEM. All fresh samples (i.e. evaluated with ESEM immediately after their positioning in the cavity) of both cements have shown a very good marginal adaption and have resulted in no marginal gap. The samples after 24 hours had an extensive formation of precipitates both on the surface of the cement and on the dentine, until all surfaces were completely covered. The EDX analyses of both cements have shown peaks of Ca, Si, Ba and Al in the fresh samples. The EDX analyses of both cements after 24 hours instead showed the occurrence of peaks of P together with peaks of Ca, while peaks of Ba and Al were virtually never visible. Traces of Si and Na and CI are evident. The latter are due to the solution. The occurrence of peaks of Ca and P confirms the formation of apatite precipitates and also confirms the high bioactivity of the cements. It is surprising that the resin-containing cement has a higher number of areas with these peaks. The result is a higher bioactivity of composition A with respect to wTC-Ba. The occurrence of Ba and Al peaks also confirms that the layer of apatite precipitates is uniform and completely masks the underlying cement. The edge of the restorations is in practice hidden by the precipitates.

Figure 7 shows an ESEM/EDX image of the filling made with composition A. The perfect marginal adaption and interface between dentine and cement may be noted. Figure 8 shows the EDX spectrum of the filling with composition A. Ca, Si, S, A, (components of the cement) and Na, Cl and P present in the solution may be detected.

Figure 9 shows an ESEM/EDX image of the filling made with the wTC-Ba. A good marginal adaption and the absence of gaps may be noted at the interface between restoration and dentine. Figure 10 shows the EDX spectrum of the filling with wTC-Ba. Ca, Si, S, Al (components of the cement) and Na, Cl, P present in the solution are detected.

Figures 11 and 12 show two ESEM/EDX images of the filling made with composition A after a 24 hour immersion in DPBS . Apatite precipitates and the complete disappearance of the margin, hidden by the precipitates may be noted. Figure 13 shows the EDX spectrum of the filling made with composition A after a 24 hour immersion in a DPBS solution. The P and Ca peaks may be noted. Si is reduced until it completely disappears. Ba is also nearly invisible.

Figures 14 and 15 show two ESEM/EDX images of the filling made with wTC-Ba after a 24 hour immersion in DPBS. This cement also produced many apatite deposits even if to a lesser extent with respect to composition A. Figure 13 shows the EDX spectrum of the filling made with wTC-Ba after a 24 hour immersion in a DPBS solution. Ca and P were detected. All other spectra are virtually absent. Traces of Na and Cl .

Example 10

Cell culture

Before seeding the cells, the discs of material were arranged on a plate with 24 culture wells and treated for 2 hours with an antibiotic/antimycotic solution (10000 U penicillin, 10 pg streptomycin, 25 \ig amphotericin B per mL) , washed twice in PBS (phosphate saline buffer) and finally pre-wetted with a culture medium containing 10% fetal bovine serum (FBS) for 24 hours at a temperature of 37 °C to simulate the in vivo conditions at the time of implant when the proteins rapidly coat the surface of the material (Sawyer AA, Hennessy KM, Bellis SL. The effect of adsorbed serum proteins , RGD and proteoglycan-binding peptides on the adhesion of mesenchymal stem cells to hydroxyapatite . Biomaterials 2007; 28: 383-392).

SaOS-2 cells (Istituto Zooprofilattico, Brescia, Italia) were cultured with D-MEM with the addition of 10% v/v of heat inactivated bovine fetal serum (FBS) , 1% penicillin-streptomicin and 2 mM L-glutamine, in a moist atmosphere with 5% C0₂ at a temperature of 37°C.

To test the growth of the cells on the sample discs, 5 x 10⁴ cells/cm² were seeded on the cement discs in microplates with 24 wells and cultured up to 7 days in 1 mL of complete medium.

Cell viability

Alamar blue dye (Biosource International) was used for cell viability. After 24 hours, 72 hours and 7 days, Alamar reagent was added 1:10 v/v to the culture wells for 4 hours . The fluorescence was then read at wavelengths of 490 nm excitation - 540 nm emission by using a Cytofluor fluorimeter 2350 (Millipore Corporation, Bedford, MA, USA) . The results were expressed as relative fluorescence units (RFU) . The cells were then plated on polystyrene (TCPS) culture wells, which served as a control. The statistical analysis was performed with the Windows StatView™ 5.0.1 software (SAS Institute Inc., Cary, NC, USA). The results are shown as the mean of six tests ± standard error, and the differences were analysed by using a Wilcoxon test with a significance level of p<0.05. Table 6

Example 11

Table 7 summarises the means of the polymerisation depth.

Table 7

wTC-Bi +Res (50H+50T) is different from Composition

A only by comprising bismuth oxide instead of barium sulphate (in the same weight percentages) .

Example 12

The following compositions were prepared by mixing the calcium-silicate cement powder with the resin component on a glass plate.

Composition 1: 1 g of wTC-Ba + 800 μΐ, (corresponding to about 1.03 grams) of HTP.

Composition 2: 1 g of FTC-Ba + 800 μΐ; (corresponding to about 1.03 grams) of HTP. wTC-Ba indicates a powder mixture of Portland cement CEM I (Aalborg Danimarca) (80% by weight) and barium sulphate (20% by weight) ; FTC-Ba indicates a powder mixture of Portland cement CEM I (Aalborg Denmark) (79% by weight) , sodium fluoride (1% by weight) and barium sulphate (20% by weight) ; HTP indicates the following mixture: (for 10 g) 4g of PAA-co-M (40%) + 6g of HT (60%) [consisting of 3g Hema (50%) + 3g Tedgma (50%)] + 0.1 g EDBMA (1%)+ 0.25 g CQ (0.25%).

The compositions obtained thereby were positioned within PVC moulds having a diameter of 8 mm and 1.6 mm and were polymerised, after the application of a transparent polyester matrix (Directa matrix strips) with the use of an Antos led lamp.

Each sample was polymerised on both greater surfaces (Composition 1, 30 seconds per side; Composition 2, 100 seconds per side). After the removal from the mould, each sample was immersed in 10 ml of double distilled water within a sealed closed container and maintained in an incubator at a temperature of 37°C.

The medium was sampled from each container and replaced with 10 ml of double distilled water at the preset times (3 hours, 1 day and 7 days) . The pH of each sampled medium was measured and, after having separated the medium in two containers of the same volume, the concentrations of calcium and fluoride ions were measured. The results are shown in the following tables 8a and 8b. Table 8a

Table 8b

Example 13

Chemical characterisation by means of micro-Raman spectroscopy and ATR-FTIR

Anhydrous powder: Raman spectroscopy

In the present example: wTC-Ba indicates a mineral powder having the composition of the mineral powder of example 2 (as also specified above); wTC-Ba+Res (50H+50T) indicates Composition A.

The Raman spectrum of the anhydrous wTC-Ba cement (Figure 4a) shows the bands of alite (at 855, 539-518 cm^"1, silicate ion vibrational modes) , belite (at 855- 845, 550-539-518 cm^-1, silicate ion vibrational modes), calcium carbonate (at 1086 cm^"1, carbonate ion stretching mode) , anhydrite (at 1016 e 677 cm^"1, sulphate ion stretching and deformation modes) , gypsum (at 1004 cm^-1, sulphate ion stretching mode) and barium sulphate (at 1167, 1141, 648-618, 461-456 cm^"1, sulphate ion stretching mode) (Tarrida et al . 1995; Sarma et al . 1998; Potgieter-Vermaak et al . 2006; Martinez-Ramirez et al. 2006; Black L et al . 2006; Gastaldi D et al . 2007). Anhydrous powder: IR spectroscopy

The IR spectrum of the WTC-Ba cement powder (Figures 2a and 3a) shows weak bands at 1465 and 1420 cm^"1 which are typical of the carbonate ion (calcium carbonate) (Stepkowska et al . 2005), at 930 (flex), 874 and 847 cm^"1, typical of the stretching vibrations of the silicate with poorly polymerised tetrahedra in the crystalline structure of the tricalciumsilicate (3CaOSi0₂, alite) (930) and of the dicalciumsilicate (2CaOSi0₂, belite) (874 and 847 cm^"1) and at 510 (more intense) and 450 cm^"1, typical of the deformation vibrations, again of the silicate ion (Hughes et al . 1995; Delgado et al . 1996; Mollah et al . 2000; Lecompte et al. 2006; Dominguez et al . 2008; Ylmen et al . 2009; Garcia Lodeiro et al . 2009; Taddei et al . 2009;). There are also bands at 1183, 1126, 1082 and 980 cm-1 due to the stretching vibrations of the sulphate ion of the barium sulphate, as well as bands at 635 and 610 cm^"1, typical of the deformation vibrations of the same ion. There is also a band at 675 cm^'1, that may be due to a deformation vibration of the sulphate ion in the calcium sulphate in the form of anhydrite or gypsum. In this case it cannot be established which of the two compounds it is, because the other calcium sulphate bands are covered by those of barium sulphate present in a greater amount .

Raman spectra detected on the surface of the cements during the ageing in DPBS

After one day of ageing in DPBS, the spectrum detected on the surface of wTC-Ba+Res (50H+50T) (Figure 4c) shows the presence of new bands (present neither in the spectrum of wTC-Ba, Figure 4a, nor in the spectrum of the resin, Figure 4b) at 1070 cm^-1 (stretching mode of the carbonate ion in a carbonate-apatite of the B type) , 964 cm^"1 (stretching mode of the phosphate ion) , 610-595-584 and 450-435 cm^"1 (deformation mode of the phosphate ion) , due to a carbonate-apatite of the B type (Nelson et al . 1982). The bands of cement at 855 cm^"1, of barium sulphate at 988 cm^"1 and of the resin at 1608 cm^"1 (stretching mode of the C=C bond) , 1458 and 1286 cm^" ¹ (deformation mode of the CH₂ group) are still visible, even when weak.

The bands at 1087 and 282 cm^"1 detect the presence of calcium carbonate in the form of calcite (Martinez- Ramirez et al. 2006) . The band of anhydrite is no longer visible and at the same time the gypsum band is intensified; this behaviour can be explained by considering that the anhydrite is hydrated producing gypsum.

The hydration products of the calcium silicate containing cements are hydrated silicate (C-S-H gel) , ettringite and calcium hydroxide. The C-S-H is poorly visible in Raman because it gives a broad and poorly intense band at about 670 cm^-1 (Tarrida et al . 1995), due to the amorphous nature of this component. For the tested cements, this band has been observed in the spectra detected in the cements (see hereinafter) . This band has been observed following the ageing in DPBS and HBSS of the wTC cement (Taddei P et al . 2009) and in particular it has been observed that as ageing proceeds, its intensity increases parallelly to the decrease of the intensity of the band at 855 cm^"1 (Taddei et al . 2009) .

Ettringite is usually visible very well in Raman, with a band of about 990 cm^-1 (Black et al . 2006); this band has also been detected during the ageing of the wTC cement (Taddei et al. 2009); in the case of the tested cements, the ettringite is not detectable due to the overlapping with the band of the barium sulphate at 988 cm^-1. The calcium hydroxide (portlandite) characterised by a band at 360 cm^-1 (Martinez-Ramirez et al . 2006) has not been detected on the surface of the cement, according to what has previously been reported (Taddei et al. 2009): this component is scoured by the storing means, which accordingly increases considerably in its pH.

After one day of ageing in DPBS, the spectrum detected on the surface of the wTC-Ba cement (Figure 5b) shows, among the bands assigned to apatite, only that at 964 citi-l and in any case with a weaker intensity with respect to the sample containing the resin and treated in the same conditions (Figure 4c) . At the same time, the bands of the cement and of the barium sulphate are visible with a higher intensity. The same considerations as for the composite cement apply to the hydrated silicate (C-S-H gel), the ettringite and the calcium hydroxide. Also in this case the bands of calcite (at 1086, 715 and 282 cm^-1) and gypsum are visible.

The trend of the spectra indicated that the apatite deposit is thicker on the sample of wTC-Ba+Res (50H+50T) than on wTC-Ba. It should be observed that at this stage, the deposit is still uneven on both cements: the band of the apatite at 964 cm^-1 has been observed in only 3 spectra of the 5 detected on the surface of wTC- Ba and only in 4 of the 5 for wTC-Ba+Res (50H+50T) .

From the quantitative standpoint, the intensity ratio I964 I855 (ratio between the intensities of the Raman bands at 964 and 855 cm^-1) was detected as spectroscopic marker of the thickness of the apatite deposit and therefore of the bioactivity. As may be noted from Figure 6, after one day of ageing in DPBS this ratio is significantly higher than for wTC- Ba+Res (50H+50T) .

A similar behaviour was observed after 14 days of ageing in DPBS ; the ratio I964 I855 increases for both samples (i.e. it increases the thickness of the deposit) and is maintained significantly higher for wTC- Ba+Res (50H+50T) ; from a qualitative standpoint it may be observed that in the spectra of both samples (Figures 4d and 5c) the bands of the cement at 855 cm^-1 and of barium sulphate at 988 cm^-1 are still visible, even if with greater intensity on wTC-Ba, suggesting that on its surface, the apatite deposit is thinner. The spectrum on the sample wTC-Ba+Res (50H+50T) no longer shows the bands of this latter component, suggesting that the thickness of the apatite layer has considerably increased. Gypsum and calcite have been detected on both samples.

After 28 days of ageing in DPBS, the spectra detected on the surface of both the samples (Figure 4e and 5d) no longer show the band of the cement at 855 cm^" ¹, while the barium sulphate band is still visible at 988 cm^-1. At this stage, the thickness of the apatite deposit becomes comparable in the two samples or rather is higher on the experimental cement wTC- Ba+Res (50H+50T) , for the lower intensity with which the band at 988 cm^"1 appears (Figure 4e) .

Claims

1. A composition comprising from 60% to 85% by- weight, with respect to the total weight of the composition, of particles of a mineral calcium-silicate material and from 10% by weight, with respect to the total weight of the composition, of a polymerisable resin; the percentage by weight of the particles of the mineral calcium-silicate material, with respect to the total weight of the composition, is higher than the percentage by weight of the polymerisable resin, with respect to the total weight of the composition; the mineral calcium-silicate material comprises at least 30% by weight, with respect to the weight of the mineral calcium-silicate material, of the sum of tricalcium silicate and dicalcium silicate; said polymerisable resin comprises at least 5% by weight, with respect to the weight of the polymerisable resin, of a polymerisable organic monomer;

the organic monomer has a partition coefficient

(LogP) either lower than or equal to 1.2.

2. The composition according to claim 1, wherein the polymerisable resin has a molar fraction of at least 0.1 of a cross-linking agent adapted to react with the organic monomer during the polymerization of the organic monomer itself.

3. The composition according to claim 1 or 2, wherein the cross-linking agent is a cross-linking monomer having at least two vinyl moieties.

4. The composition according to claim 3, wherein the polymerisable resin has a molar fraction lower than 0.53 of the cross-linking monomer; the cross-linking monomer has two methacrylic acid esters.

5. The composition according to claim 3 or 4, wherein the cross-linking monomer has the following structure:

CH₂=C (R⁴) COO-R^x-OOC (R⁵) C=CH₂

wherein R¹ is selected from the group consisting of: Ci-C₈ alkyl, Ci-C₈ alkenyl, C₂-C₇ ether, C₃-C₇ diether; R⁴ and R⁵ are independently selected from the group consisting of: H, C₁-C4 aliphatic; and more in particular, the cross-linking monomer is TEGMA.

6. The composition according to any of the preceding claims, wherein the polymerisable resin comprises at least 20% by weight, with respect to the weight of the polymerisable resin, of a substantially hydrophobic monomer, which is adapted to react with the organic monomer during the polymerization of the organic monomer; the substantially hydrophobic monomer has a partition coefficient (LogP) higher than 1.

7. The composition according to any of the preceding claims, wherein the polymerisable resin comprises from 30% to 75% by weight, with respect to the weight of the resin, of the organic monomer; the organic monomer has at least one vinyl moiety, which reacts during the polymerization, and at least one moiety selected from the group consisting of: hydroxy (-OH) , carboxy (-COOH) , sulphuric, sulphurous, amine; the organic monomer has a partition coefficient lower than 1.

8. The composition according to any of the preceding claims, wherein the organic monomer is an ester of an acid selected from the group consisting of: acrylic acid, methacrylic acid.

9. The composition according to any of the preceding claims, wherein the organic monomer has the following structure:

CH₂=C(R³)COO-R²

where R² is a C₁-C4 hydroxy-aliphatic; R³ is selected in the group consisting of: H, C₁-C₂ aliphatic.

10. The composition according to any of the preceding claims, wherein the organic monomer is selected from the group consisting of: HEMA, HPMA, PE TA, 4-META.

11. The composition according to any of the preceding claims, and comprising a photoinitiator.

12. The composition according to any of the preceding claims, wherein the mineral calcium-silicate material comprises at least 40% by weight, with respect to the weight of the mineral calcium-silicate material, of the sum of tricalcium silicate and dicalcium silicate .

13. The composition according to any of the preceding claims, wherein the mineral calcium-silicate material comprises at least 40% by weight, with respect to the weight of the mineral calcium-silicate material, of tricalcium silicate and at least 7% by weight, with respect to the weight of the mineral calcium-silicate material, of dicalcium silicate.

14. The composition according to any of the preceding claims, wherein the mineral calcium-silicate material is Portland cement .

15. The composition according to any of the preceding claims, and comprising BaS0₄.

16. A composition comprising from 60% to 85% by weight, with respect to the total weight of the composition, of particles of a mineral calcium-silicate material and from 10% by weight, with respect to the total weight of the composition, of a polymerisable resin; the percentage by weight of the particles of the mineral calcium-silicate material, with respect to the total weight of the composition, is higher than the percentage by weight of the polymerisable resin, with respect to the total weight of the composition; the mineral calcium-silicate material comprises at least 30% by weight, with respect to the weight of the mineral calcium-silicate material, of the sum of tricalcium silicate and dicalcium silicate; said polymerisable resin comprises at least 5% by weight, with respect to the weight of the polymerisable resin, of a polymerisable organic monomer; the organic monomer has at least one vinyl moiety, which is adapted to react during the polymerization, and comprises at least five carbon atoms and at least one group selected from the group consisting of: hydroxy, carboxy, sulphuric, sulphurous, aminic.

17. A composition comprising from 60% to 85% by weight, with respect to the total weight of the composition, of particles of a mineral calcium-silicate material and from 10% by weight, with respect to the total weight of the composition, of a polymerisable resin; the percentage by weight of the particles of the mineral calcium-silicate material, with respect to the total weight of the composition, is higher than the percentage by weight of the polymerisable resin, with respect to the total weight of the composition; the mineral calcium-silicate material comprises at least 30% by weight, with respect to the weight of the mineral calcium-silicate material, of the sum of tricalcium silicate and dicalcium silicate; said polymerisable resin comprises at least 5% by weight, with respect to the weight of the polymerisable resin, of a polymerisable organic monomer; the organic monomer is amphiphilic .

18. The composition according to any of the preceding claims, and comprising up to 30% by weight, with respect to the total weight of the composition, of the polymerisable resin.

19. The composition according to any of the preceding claims, and comprising up to 25% by weight, with respect to the total weight of the composition, of the polymerisable resin.

20. The composition according to any of the preceding claims, for dental use.

21. The composition according to claim 20, for making either retrograde root fillings, or fillings of side or furcation perforations.

22. Use of a composition according to any of claims from 1 to 19 , for preparing a product for endodontic use in mammals .

23. Use of a composition according to any of claims from 1 to 19, for preparing a product to be used in retrograde root fillings or side perforation fillings.

24. Use of a composition according to any of claims from 1 to 19, for preparing apatatite, the use providing the introduction of the composition into phosphate containing fluids .