WO2020058927A1

WO2020058927A1 - Removable dental appliances

Info

Publication number: WO2020058927A1
Application number: PCT/IB2019/057973
Authority: WO
Inventors: David Philip; Alberto Raffaele ZANVIT
Original assignee: Dal 18 S.R.L.
Priority date: 2018-09-21
Filing date: 2019-09-20
Publication date: 2020-03-26

Abstract

The present invention relates to a material for producing an appliance for use in the oral cavity comprising luminescent substances suitable for the treatment of dental diseases and periodontal tissues and for cosmetic and aesthetic purposes.

Description

REMOVABLE DENTAL APPLIANCES”

The present invention relates to a material for producing a removable appliance for application in the oral cavity comprising luminescent substances suitable for the treatment of dental pathologies and periodontal tissues and for cosmetic and aesthetic purposes.

The procedures for the production of materials suitable for the production of the final luminescent removable appliance are also described.

The need is strongly felt in the field for having removable dental systems capable of supporting gels produced with monofunctional or multifunctional active ingredients with an immunomodulating/stimulating, anti-inflammatory, anti-microbial, antiviral, antibacterial action, which can be activated through photochemical reactions, produced with polymeric compositions that overcome the constraints currently present on the market such as, for example, the need for having an externally powered light source for the whole period of the presence of the appliance in the patient's mouth.

This limitation, on the one hand, forces the patient to remain for a few hours substantially immobile in a medical-dental clinic, and on the other hand, to renounce possible treatment with active ingredients having a slow and controlled release that can also be effected at the same patient's home.

Aesthetic dental problems due to dental malpositioning, various kinds of dyschromia and dental erosion, can give phonetic, relationship and psychological problems. These disorders can be temporarily resolved with removable aesthetic templates. Templates can in fact change the shape and position of the teeth and/or their colour, based on the aesthetic needs of the patients.

In the gnathological field, teeth grinding or their malpositioning can cause an abnormal consumption of the tooth enamel, posture disorders or pain in the skeletal muscle system. Bruxism or grinding of the teeth is the involuntary clenching of the teeth that occurs more often during the night.

In most cases, the resolution of masticatory disorders is a "bite".

A "bite" is an occlusal plate with the shape of a template that must be placed between the two dental arches for a period of time that varies according to the pathologies encountered and allows the jaw muscles to relax and prevents rubbing of the teeth.

A "bites" is a remedy that allows the correct occlusal space to be maintained, releasing the force exerted by the muscles on the plate rather than on the teeth and relaxing the jaw and cervical muscles, avoiding deterioration of the teeth themselves.

"Bites" with photoluminescence characteristics allow the areas of greater dental pressure, which can be identified thanks to a lower luminous effect due to the lesser thickness of the material, to be evaluated better and more rapidly.

As these appliances are worn mainly during rest hours at night, the feature of photoluminescence makes it easy to find the appliance if it comes out of the oral cavity.

Tooth whitening is a procedure suitable for making the teeth appear whiter. The treatment can be effected directly in the dental clinic or by the patient himself at home.

The gels used contain hydrogen peroxide or carbamide peroxide in different concentrations depending on the type of whitening to be performed. These whitening agents can be activated by any light sources that enhance their effectiveness and favour their action in depth. Once the gel has been activated by specific light sources, it releases free radicals that are able to penetrate into the structure of the tooth triggering redox reactions that break down the molecules of the stains into smaller, colourless and easily eliminable compounds.

For home treatment, the dentist creates customized templates in which the patient inserts small doses of whitening gel, and then applies them to the dental arches. The templates must be kept in the mouth for a variable time depending on the result to be obtained.

Periodontal disease is a disease with a bacterial etiology that affects the supporting tissues of the tooth: alveolar bone, periodontal ligament, gum and root cement. Neglecting this disease leads to the progressive destruction of the supporting tissues up to the loss of the dental elements.

The gum is a soft tissue that surrounds the teeth and covers the alveolar process.

The predominant tissue in the gum is connective tissue, consisting of fibroblasts, fibers, vessels, nerves and matrix: the fundamental amorphous substance that allows the transporting of water, electrolytes, metabolites and nutrients within the connective tissue.

Absorption through the connective tissue reveals its importance, considering that there is a wide range of substances capable of overcoming the natural barrier of the gum. An absorption of this type acts with a slow accumulation mechanism. Furthermore, the substances thus absorbed are in no way modified/damaged by the stomach or intestine, as would be the case with gastric or intestinal absorption and, at the same time, do not cause damage to the gastric wall.

Photodynamic therapy (PDT) is a treatment that involves three key components: a photosensitive substance, light and tissue oxygen to treat inflammatory processes.

This technology has undoubted advantages such as the targeted release of active ingredients on specific targets, the reduction of possible side-effects compared to oral intake and the modulation of release kinetics.

Photochemistry is that part of chemistry that studies the permanent chemical effects of the interaction between matter and electromagnetic radiations in the spectrum between the ultraviolet and the infrared, passing through the visible. The quantum theory has provided satisfactory explanations of the phenomena involved in it. By absorbing a photon having an appropriate wavelength, a molecule is excited to a stable or unstable state in which, depending on the wavelength of the radiation absorbed, the energy can be stored as energy associated with rotational, vibrational or electronic degrees of freedom.

Photochemical reactions therefore require a light source that emits wavelengths corresponding to an electronic transition in the reagent.

Photochemical reactions are valuable in organic and inorganic chemistry as they proceed differently with respect to thermal reactions.

The term luminescence means the emission of light not directly attributable to incandescence by a material previously exposed to some excitation method determined by the absorption of energy produced in various forms ("IESNA RP- 16-1996 -Nomenclature and Definitions for Illuminating Engineering ").

Luminescence is classified in relation to the energy process that determines the excitation:

a) from biological processes: bioluminescence;

b) electronics: cathodoluminescence;

c) from chemical reactions: chemiluminescence; d) from a fixed or variable electric field: electroluminescence;

e) from electromagnetic radiation: fluorescence and photoluminescence (phosphorescence);

f) from acoustic energy: sonoluminescence;

g) from temperature changes: thermoluminescence;

h) from subatomic particles: radioluminescence

i) from mechanical energy: triboluminescence.

A crystal is characterized by a periodic arrangement of the atoms according to well-defined symmetries. Any deviation from the periodic structure is a defect.

The extrinsic defects of the crystal can be grouped into two classes: the substitutional ions, for example Fe, Ge, Cr, Al, Ag, Sr, and the interstitial ions that determine their energy excitation.

Crystalline solids can be classified as insulators, semiconductors and metals based on their electrical properties. What distinguishes them is the possible presence (and therefore the amplitude) of a gap between the higher energy occupied level (Fermi level), called conduction band, and the unoccupied lower energy level, called valence band.

The insertion of interstitial ions, typically rare earth, in the formulation of photoluminescent pigments is called "doping" of the material. Furthermore, different types of rare earth inserted in other oxides contribute to the fluorescence effect.

Among all the various types of defects, those that affect the phenomenon of luminescence (phosphorescence and fluorescence) are point defects. The latter can be negative vacancies, interstitial negative ions or substitutional impurities.

The presence of point defects in a crystalline solid material leads to the breakdown of the periodic potential of the crystal around the defect itself, which causes the creation of electronic states within the gap. These are localized states commonly defined as trap levels, if they receive and transfer electrons in the conduction band, or recombination centres, if they receive electrons from the conduction band and transfer them in the valence band or receive gaps from the valence band and transfer them to the conduction band. The function of acceptors of positive or negative charges by point defects is related to their associated probability of trapping free electrons and the position within the gap, commonly defined as trap depth.

An electron on a trap level is in a metastable state. The transition from this level to the fundamental state is in fact prohibited by the selection rules and relaxation times, which can be extremely long (at room temperature even in the order of billions of years).

In the case of excitation caused by luminous photons, a first classification of the luminescence phenomena can be made based on the time that lapses between the absorption of the radiation and the emission of light. If the time is less than 10 nanoseconds (10 -8 sec), this is fluorescence, otherwise it is photoluminescence (phosphorescence).

Photoluminescent inorganic compounds include strontium aluminate (SrAl) oxides and other proprietary inorganic compounds, with photometric characteristics that far exceed those of zinc sulfide compounds, as they offer a brighter and more durable photoluminescence, with a varying excitation spectrum from 200 nm to 470 nm, with a fairly uniform spectral distribution ranging from 250 nm to 420 nm and an excitation peak of 360 nm, and with an spectral emission distribution that varies from 390 nm to 550 nm, with an emission peak of 540 nm.

The excitation spectrum of the new photoluminescent inorganic compounds includes both the component of the non-visible electromagnetic spectrum, in the UV (near UV) range from 200 nm to 400 nm, divided into UV-C (200-280 nm), UV-B (280-3 l5nm) and UV-A (315-400 nm), and also the visible electromagnetic spectrum component in the range from 400 nm to 470 nm.

UV-A rays are the most interesting for the purposes of the present invention, as they are able to excite indifferently and simultaneously both fluorescent pigments and photoluminescent inorganic compounds.

At the end of the saturation by luminous excitation, the photoluminescent inorganic compounds can have an extinction time ("afterglow" time required for having a brightness equal to a masb = 0.032 millicandela/m , about 100 times the limit of human perception in absolute darkness), which can reach over 48 hours.

Another particular feature that distinguishes photoluminescence from fluorescence is the different behavior of the two phenomena with respect to temperature. Whereas, in fact, the intensity of the radiation emitted by photoluminescence increases with an increase in temperature, fluorescence is not sensitive to temperature variations.

It is not entirely correct to distinguish phosphorescence (photoluminescence) from fluorescence based on the time between absorption and emission, or in relation to the different behaviour of the two phenomena with respect to temperature. The real discriminating factor between fluorescence and phosphorescence is the presence or absence of trap levels.

The energy transferred by electromagnetic radiation is transferred to the electrons which, for the most part, are promoted from the valence band to the conduction band. The electrons in the conduction band and the vacancies in the valence band are now free to move within the lattice and can be "captured" by the trap levels and recombination centres respectively. The metastable nature and the depth of the trap level (centre T) prevent the electrons from making a transition into BV (valence band) or BC (conduction band).

The relaxation process, and therefore the emission of electromagnetic radiation, occurs because the electron acquires sufficient energy for returning to the conduction band and from here it decays radiatively on a recombination centre (centre R).

An electromagnetic radiation having an appropriate wavelength can therefore induce the passage of electrons from the optically sensitive traps to the conduction band.

In this case the emptying speed of the traps is related to the rate of photons incident on the crystal (i.e. to the lighting power density) and to the photon capture impact section of the trapped electrons.

An OSL signal (optically stimulated luminescence) therefore consists of a decay curve of the intensity emitted which, in the simplest case, will have an exponential trend. In the presence of two or more trap levels, the decay expression is the sum of different exponential trends.

If the traps in question are not deep enough to render the possibility of re entrapment null, there are also possible trap levels that can enter into competition with the recombination centres by capturing the free electrons. This phenomenon helps to modify the signal emitted, reducing its initial intensity and modifying its trend. A final observation relates to the possibility of there being various levels of recombination centres in the crystal. It should be borne in mind that in a real crystal all the factors that give rise to the complex processes described above coexist, i.e. multiple trap levels and recombination centres, competitive traps and non-radiative recombination centres all contribute to a kinetics of a different order than the first, that is, with only one trap level in which the intensity of the radiation emitted over time is linked to the change in concentration of the electrons in the traps.

Although luminescent materials in the solid state, liquid state and gaseous state are known, in this context only inorganic fluorescent crystals and photoluminescent (phosphorescent) crystals will be considered, which can be incorporated into different materials, including plastic films and rigid moulded plastic.

The present invention relates to the use of at least one photoluminescent substance and/or at least one fluorescent substance for the production of a dental appliance.

An objective of the present invention is to provide a system for the care or aesthetic treatment of a subject’s teeth that overcomes the disadvantages of the prior art described above.

The object of the present invention relates to a material for the production of a dental appliance comprising a mixture (M) of:

i. at least one biocompatible polymer; and at least one of

ii. at least one photoluminescent substance which is an inorganic crystal having a particle size (D50) ranging from 5 to 65 micrometers;

iii. at least one fluorescent substance which is an inorganic crystal having a particle size (D50) ranging from 2 to 10 micrometers.

A further object of the present invention relates to a method for producing the dental appliance comprising a material as defined above, said method comprising a step for forming the appliance, or at least a part thereof, in a definitive or intermediate form, by means of a 3D printing technique and, optionally, a post-processing step of the appliance or part of the appliance obtained from the 3D printing.

An object of the present invention relates to a non-therapeutic method for improving the aesthetic characteristics of a subject's teeth, wherein said method comprises the application of the dental appliance as described above.

An object of the present invention relates to a photosensitive substance for use in the treatment of a disease or disorder of the oral cavity, preferably of the teeth, wherein said treatment comprises photodynamic therapy (PDT) in which energy is supplied to said photosensitive substance for the formation of active species deriving from oxygen, wherein the dental appliance as described above is used as a light source for at least partially providing the energy for the activation of the photosensitive substance.

A further object of the present invention relates to a mixture (M) comprising:

i. at least one polymer or copolymer and at least one of

ii. at least one photoluminescent substance;

iii. at least one fluorescent substance,

wherein:

- the polymer or copolymer i. is at least one of PETG (glycol- modified polyethylene terephthalate), EVA (ethylene vinyl acetate), PMMA (polymethylmethacrylate), SAN (acrylonitrile styrene copolymer), SBS (styrene and butadiene copolymer), PE (polyethylene) in various types: HDPE (high- density polyethylene,), LDPE (low-density polyethylene), LLDPE (linear low- density polyethylene), PP (polypropylene), PU (polyurethane), PLA (polylactic acid), GPPS (polystyrene crystal), a polyacrylate cross -linkable with UV light with a wavelength ranging from 3l5nm to 400 nm, their mixtures or copolymers; - the photoluminescent substance ii. is an inorganic crystal selected from photoluminescent pigments consisting of, or comprising, strontium aluminate oxides having a particle size (D50) ranging from 5 to 65 micrometers;

- the fluorescent substance iii. is an inorganic crystal having a particle size (D50) ranging from 2 to 10 micrometers selected from non-metal salts, for example fluorescent phosphorous salts (phosphates) such as for example: ambligonite, anapaite, arctite, autunite, bergenite, foggite, furongite, herderite, nacapaite, apatites, including, without limitation, hydroxyapatite (medium fluorescence), fluorapatite and strontium-apatite (high fluorescence) and the like, and pigments consisting of rare earth oxides with coloured luminescence activated by long- wave UV rays such as aluminum barium magnesium oxide (CAS N. 63774-55-0), Al₂Ce₂Mg₂0iiTb₂ (CAS Nr.67542-72-7), yttrium vanadium phosphate oxide doped with europium and dysprosium (CAS Nr. 100403-11-0), B4Sr07 doped with europium (CAS Nr. 71786-49-7), yttrium oxide doped with europium (CAS Nr. 68585-82-0), calcium fluoride chloride phosphate (CAS Nr. 75535-31-8) and di-zinc orthosilicate doped with manganese (CAS Nr. 68611-47-2).

Within the scope of the present invention, the types of polyethylene (PE) can be distinguished on the basis of the classification provided in "Handbook of Polyethylene: Structures, Properties, and Applications", A. Peacock, CRC Press, 2000, pages 2-3: HDPE indicates a high-density polyethylene, density range approximately from 0.94 to 0.97 g/cm , LDPE indicates a low-density polyethylene, density range approximately higher than 0.90 and less than 0.94 g/cm ), LLDPE (linear low-density polyethylene, density range approximately from 0.90 to 0.94 g/cm³).

The particle-size distribution of the luminescent pigments lies within a range that represents the distribution curve, for example 2-5 pm, 5-10 pm, 10-20 pm, 20-40 pm and 40-65 pm.

The particle- size distribution can be determined by any method known to the persons skilled in the art such as, by way of non-limiting example, by means of the frequency distribution method with calibrated selective sieves, stacked and with decreasing mesh sizes from the upper sieve to the lower one.

The weight of the fraction found on each individual sieve is then determined; the pigments are then grouped into groups (ranges) they belong to (for example, 2-5 pm, 5-l0pm, 10-25 pm, 20-45 pm and 40-65 pm).

The particle-size distribution is determined in relation to the weight of each single fraction within a range, which reveals the percentage frequency with which the dimensions of the pigments belonging to a single range deviate from the value of the average diameter (D50) with the formula å pd/lOO, wherein p is the quantity % and d is the size of the mesh.

Within the scope of the present invention, in order to obtain the efficiency and uniformity of therapeutic treatment, and also for aesthetic purposes, the light radiation must be emitted homogeneously from the material.

On the one hand, the light intensity of the light emitted is directly proportional to the exposure surface of the photoluminescent or fluorescent crystal, it is therefore preferable to use relatively large particles in order to maximize the exposure surface. The use of large pigment particles, on the other hand, leads to the formation of gaps between the individual particles. In the presence of gaps, the light is emitted non-uniformly, therefore the material is not suitable for the application of the present invention.

In order to obtain a uniform brightness and adequate physical properties

(such as hardness and wear resistance), it is advantageous for the pigments to be homogeneously dispersed in the polymer matrix. The particle size of the pigments greatly affects the dispersion of the pigments in the polymer matrix. In relation to the type of application and the transparency or otherwise of the polymeric materials containing the luminescent pigments, the dimensions of the pigments are therefore fundamental for obtaining the desired result. It has been found that photoluminescent inorganic crystals having a particle size (D50) ranging from 5 to 65 micrometers and inorganic crystals having a particle size (D50) ranging from 2 to 10 micrometers, are particularly suitable for the application according to the present invention, as they allow materials to be obtained that emit light radiation in a way perceived as uniform by an observer.

In the material of the present invention, the photoluminescent inorganic crystals preferably have a particle size (D50) within the range of 20 to 60 micrometers, more preferably from 30 to 50 micrometers and/or the inorganic fluorescent crystals have a particle size (D50) within the range of 2.5 to 6 micrometers, more preferably from 3 to 5 micrometers.

It has also been found that the compositions according to the present invention do not leak the pigments, therefore, during the use of the dental appliance, the inorganic salts are not transferred from the appliance to the body of the wearer of the appliance. This is particularly advantageous considering that the dental appliance comprising the material of the present invention can be used for a prolonged time, for example during sleep, and for several days or months, hence the migration of chemical elements from the appliance to the wearer could result in exposure and the accumulation in the body of substances potentially harmful to health.

The tests carried out according to the standard method EN 71-3: 2013 + A3- 2018 on the materials of the invention, even after printing and after mechanical stress, concerned the potential migration of specific chemical elements potentially harmful to health and showed that migration, when detectable, is lower than the limit values set by the standard.

Polyacrylates are liquid resins with a viscosity within a wide range which, when exposed to a UV light having a wavelength ranging from 315 nm to 400 nm, crosslink and acquire a solid consistency.

"Activation" of polyacrylates refers to the point-by-point exposure of polyacrylates through a UV radiation with the wavelength indicated for a time sufficient to obtain cross-linking.

In the case of crosslinkable polymers, the luminescent pigments (ii. - photoluminescent and iii. - fluorescent) and their mixtures are dispersed in the liquid resins before the crosslinking is started, in this way the luminescent substance is incorporated into the resin at the time of crosslinking.

By way of non-limiting example, tetradecaaluminium tetrastrontium pentacosaoxide (CAS Nr. 76125-60-5) and similar substances, such as the pigments of the series G9, G8, B8 and A9 produced by AllureGlow®, can be used as type ii. pigments in the composition according to the present invention.

Unless otherwise indicated, within the scope of the present invention, the percentages and quantities of a component in a mixture refer to the weight of this component with respect to the total weight of the mixture.

Unless otherwise specified, within the scope of the present invention, the indication that a composition "comprises" one or more components or substances means that other components or substances may be present in addition to that, or those, specifically indicated.

Unless otherwise specified, within the scope of the present invention, a range of values indicated for a magnitude, for example the weight content of a component, includes the lower limit and the upper limit of the range. By way of example, if the weight or volume content of a component A is indicated as "from X to Y", wherein X and Y are numerical values, A may be X or Y or any of the intermediate values.

Within the scope of the present invention, "dental appliance" refers to an apparatus, or medical device, suitable for being applied in the oral cavity, or on part of the oral cavity, preferably on the teeth or on part of the teeth of a subject, for therapeutic purposes or for the prevention of a pathology or a disorder or for non-therapeutic purposes, such as, for example, without limitation, for purposes of aesthetic improvement also including teeth whitening.

The present invention relates to the possibility of using, also jointly, photoluminescent crystals, which have a decay time greater than 10 nanoseconds

(10 -8 sec), and fluorescent (photoluminescent) crystals, which have a decay time of less than 10 nanoseconds (10 -8 sec) and that require constant "lighting" to be visible over time, so as to generate, through their interaction, repetitive and continuous "self-feeding" events of the luminescent phenomena due to the simultaneous presence of light radiations by fluorescence and photoluminescence. Furthermore, microprismatic back-reflectors and other brightness improvement techniques can increase the luminance of the material many times.

All of this increases the resulting luminous effect, even in the absence of traps, on more than one wavelength emitted, in relation to the type of radiation necessary for activating and maintaining the photochemical reactions necessary for activating the various active ingredients hypothesized.

With the present invention, the limitations of the systems of the prior art are overcome as, once the self-feeding process of the removable dental system is activated for a few minutes and with an external light source, the subject can freely resume his activities without having to remain for a prolonged period of time in a dental clinic or medical environment.

The production of devices, such as templates or "bites", with photoluminescent materials according to the present invention can allow a deeper and faster tooth-whitening action without having to resort to external light sources.

The same application mode can also be exploited, also through photodynamic therapy (PDT), for other pathologies of the oral cavity; for example for reducing the cariogenic bacterial load, in the regulation of the pH or in the reduction of the volatile sulfur compounds (VSC) of halitosis.

Within the scope of the present invention, photodynamic therapy (PDT) refers to a therapeutic methodology which involves the use of a photosensitive substance which, once exposed to light radiations, is able to interact with body oxygen and create active species (such as peroxide radicals) that have a cytotoxic action in particular on microorganisms and/or tumour cells. As a non-limiting example, PDT is described in Ramya et al., Int J Biol Med Res. 2012; 3 (2): 1875- 1883.

In an embodiment, the present invention provides a material for producing a dental appliance comprising a mixture (M) of: i. at least one biocompatible polymer; and at least one of:

ii. at least one photoluminescent substance;

iii. at least one fluorescent substance.

In a preferred embodiment of the present invention, in said material for making a dental appliance, the mixture (M) comprises components i. and ii. or components i. and iii. or a combination of components i, ii. and iii.

In a preferred embodiment of the present invention, said material for producing a dental appliance is in the form of a sheet or film for producing a removable template for orthodontic or aesthetic purposes, of a filament or resin for 3D printing or a disk for CAD-CAM milling machines, and, more preferably, in said material the mixture (M) comprises components i. and ii. or components i. and iii. or a combination of components i, ii. and iii.

In a preferred embodiment of the present invention, in said material for producing a dental appliance the polymer i. is at least one of glycol-modified polyethylene terephthalate (PETG), ethylene vinyl acetate (EVA), polymethylmethacrylate (PMMA), polystyrene crystal (GPPS), a copolymer of styrene and butadiene (SBS), polyethylene (PE) in various types: HDPE (high- density polyethylene), LDPE (low-density polyethylene), LLDPE (linear low- density polyethylene), polypropylene (PP), a polyurethane (PET), polylactic acid, GPPS (polystyrene crystal), a polyacrylate activatable with UV light with a wavelength ranging from 315 to 400 nm and their mixtures or copolymers. Particularly preferred polymers are EVA, for embodiments that can be prepared by the user himself, PETG with phosphorescent powders for thermoforming in professional clinics and PS crystal (GPPS) with fluorescent powders for thermoforming in professional clinics. In a preferred embodiment, in the material for producing a dental appliance according to the invention, the polymer i. is a mixture of PE in various types: HDPE (high-density polyethylene), LDPE (low-density polyethylene), LLDPE (linear low-density polyethylene) and EVA in a ratio of 99: 1 to 1:99 by weight, more preferably from 5:95 to 60-:40.

In a preferred embodiment of the present invention, in said material for a dental appliance, the photoluminescent substance ii. is an inorganic crystal having a particle size (D50) ranging from 5 to 65 micrometers, selected from photoluminescent pigments consisting of, or comprising, strontium aluminate oxides. By way of non-limiting example, in the dental appliance according to the present invention, tetradecaaluminium tetrastrontium pentacosaoxide (CAS Nr. 76125-60-5) and similar substances, such as pigments of the series G9, G8, B8 and A9 produced by AllureGlow® (ETSA), can be used as type ii pigments.

In a preferred embodiment of the present invention, in said material for producing a dental appliance, the fluorescent substance iii. is an inorganic crystal having a particle size (D50) ranging from 2 to 10 micrometers selected from non- metal salts, for example fluorescent phosphorous salts (phosphates) such as: abrigonite, anapaite, arctite, autunite, bergenite, foggite, furongite, herderite, nacapaite, apatites, including, without limitation, hydroxyapatite (medium fluorescence), fluorapatite and strontium-apatite (high fluorescence) and the like, and pigments consisting of rare earth oxides with coloured luminescence activated by long-wave UV rays such as aluminum barium magnesium oxide (CAS Nr. 63774-55-0), Al₂Ce₂Mg₂0iiTb₂ (CAS No. 67542-72-7), yttrium vanadium phosphate oxide doped with europium and dysprosium (CAS Nr. 100403-11-0), B4Sr07 doped with europium (CAS Nr. 71786-49-7), yttrium doped with europium (CAS Nr. 68585-82-0), calcium fluoride chloride phosphate (CAS Nr. 75535-31-8) and di-zinc orthosilicate doped with manganese (CAS Nr. 68611-47-

2).

It has been found that, advantageously, the pigment particles are optimally dispersed in the mixture (M) when their concentration is within certain preferred ranges. In a preferred embodiment of the present invention, in said material for producing a dental appliance, with respect to the total weight of the mixture (M), the content of the photoluminescent substance ii. ranges from 0.1 to 15%, more preferably from 3.2 to 8.6%, even more preferably from 5 to 6%, by weight and/or the content of the fluorescent substance iii. ranges from 0.1 to 12% by weight, preferably from 1.5 to 5.8, even more preferably from 3 to 4%.

An embodiment of the present invention relates to a method for producing the dental appliance as described above, comprising a step for forming the device, or at least a part thereof, in definitive form or as an intermediate, through a 3D printing technique and, optionally, a post-processing step of the appliance or part of the appliance obtained from 3D printing.

In preferred embodiments of the present invention, said method comprises thermoforming from plastic films (by way of non-limiting example PETG, EVA) obtained from a compound in the form of granules, or 3D printing from plastic filaments (by way of non-limiting example PETG, ABS, SAN) obtained from a compound in the form of granules or 3D printing from liquid resins (polyacrylates) mixed by dispersion with luminescent pigments or the CAD-CAM milling of disks (by way of non-limiting example, in polymethylmethacrylate, PMMA) .

In another embodiment, the present invention relates to a non-therapeutic method for improving the aesthetic characteristics of the teeth of a subject comprising the application of the dental appliance as described above. By way of non-limiting example, said treatment can have the purpose of whitening teeth.

An embodiment of the present invention relates to a photosensitive substance for use in the treatment of a disease or disorder of the oral cavity, preferably teeth, wherein said treatment comprises photodynamic therapy (PDT) in which energy is supplied to said photosensitive substance for the formation of active species deriving from oxygen, wherein the dental appliance described above is used as a light source for providing, at least partially, the energy for the activation of the photosensitive substance. By way of non-limiting example, substances such as hydrogen peroxide, iodopovidone and chlorhexidine can be used as photosensitive substances in photodynamic therapy within the scope of the present invention.

In an embodiment, the present invention relates to the use of the material comprising the mixture (M), as described above, as a light source for at least partially providing the energy for the activation of at least one photosensitive substance in the treatment of a pathology or disorder of the oral cavity, preferably of the teeth, in which said treatment comprises photodynamic therapy (PDT).

In an embodiment, the present invention relates to a mixture (M) comprising:

i. at least one biocompatible polymer; and at least one of:

ii. at least one photoluminescent substance; iii. at least one fluorescent substance,

wherein:

- the polymer i. is at least one of glycol-modified polyethylene terephthalate (PETG), ethylene vinyl acetate (EVA), polymethylmethacrylate (PMMA), a styrene and butadiene copolymer (SBS), polyethylene (PE) in various types: HDPE (high-density polyethylene,), LDPE (low-density polyethylene), LLDPE (linear low-density polyethylene), polypropylene (PP), a polyurethane (PET), GPPS (polystyrene crystal), polylactic acid, a polyacrylate activatable, i.e. crosslinkable, with UV light with a wavelength ranging from 315 nm to 400 nm, and their mixtures or copolymers;

- the photoluminescent substance ii. is an inorganic crystal having a particle size (D50) ranging from 5 to 65 micrometers selected from photoluminescent pigments consisting of, or comprising, strontium aluminate oxides and;

- the fluorescent substance iii. is an inorganic crystal having a particle size (D50) ranging from 2 to 10 micrometers selected from non-metal salts, for example fluorescent phosphorous salts (phosphates) such as for example: abrigonite, anapaite, arctite, autunite, bergenite, foggite, furongite, herderite, nacapaite, apatites, including, without limitation, hydroxyapatite (medium fluorescence), fluorapatite and strontium-apatite (high fluorescence) and the like, and pigments consisting of rare earth oxides with coloured luminescence activated by long wave UV rays such as aluminum barium magnesium oxide (CAS Nr. 63774-55- 0), Al₂Ce₂Mg₂0iiTb₂ (CAS Nr. 67542-72-7), yttrium vanadium phosphate oxide doped with europium and dysprosium (CAS Nr. 100403-11-0), B₄Sr0₇ doped with europium (CAS Nr. 71786-49-7), yttrium oxide doped with europium (CAS Nr. 68585-82-0), calcium fluoride chloride phosphate (CAS Nr. 75535-31-8) and di-zinc orthosilicate doped with manganese (CAS Nr. 68611-47-2).

The following examples are provided for illustrating some embodiments of the invention, without limiting its scope.

The following masterbatches (MB) were produced:

a) a first plastic masterbatch "A" in granules produced with a specific material, for example in PETG or EVA, containing inert photoluminescent pigments (crystals) having a size ranging from 5 to 65 micrometers (microns), with a variable weight concentration up to a maximum of 50% compared to the total weight of "A".

By way of non-limiting example, the inert photoluminescent pigments can be tetradecaaluminium tetrastrontium pentacosaoxide (CAS Nr. 76125-60-5) and similar substances, such as pigments of the series G9, G8, B8 and A9 produced by AllureGlow®USA, LLC, California (USA).

These photoluminescent pigments have characteristics of high efficiency and durability both in the "glow" and "afterglow" phases, a high operating temperature, a more than high disintegration temperature, a high anchoring capacity with the base polymers, whether they be in the form of powder or in the form of granules (pellets);

b) The production of a second plastic masterbatch "B" in granules produced with a specific material, for example in PETG or EVA, containing inert fluorescent pigments (crystals) having a size ranging from 2 to 10 microns, with a variable weight concentration up to a maximum of 40% with respect to the total weight of "B".

By way of non-limiting example, said fluorescent pigment can be an apatite, a fluorapatite, or a pigment consisting of rare-earth oxides with coloured luminescence activated by long-wave UV rays such as aluminium barium magnesium oxide (CAS Nr. 63774-55- 0), Al₂Ce₂Mg₂0iiTb₂ (CAS Nr. 67542-72- 7), yttrium oxide vanadium phosphate doped with europium and dysprosium (CAS Nr. 100403-11-0), B₄Sr0₇ doped with europium (CAS Nr. 71786-49-7) , yttrium doped with europium (CAS Nr 68585-82-0), calcium fluoride chloride phosphate (CAS Nr. 75535-31-8) and di-zinc orthosilicate, doped with manganese (CAS Nr. 68611-47- 2).

These fluorescent pigments have characteristics of high efficiency, a high operating and disintegration temperature and a high anchoring capacity with the base polymers, whether they be in powder form or in the form of granules.

A twin-screw machine configuration is preferable, in which the inner walls and the twin-screw must be produced with specially hardened materials as the photoluminescent inorganic pigments are made of very hard materials that can cause abrasion to the internal surfaces of the extruder.

The processing temperature set is preferably higher than about l0°C (50°F) compared to that commonly used, as the photoluminescent inorganic pigments have a high thermal conductivity that contrasts with the typical physical characteristics of plastic materials that have a reduced thermal conductivity. Two separate hoppers are needed with gravimetric dosers for a correct and homogeneous distribution: the first serves to feed the base resin in pellets, the second serves to dose the phosphorescent pigments in the molten polymer. The degassing must be kept active in the last area of the extruder before the die during the whole production.

A plastic compound in granules, hereinafter referred to as "C", was then produced by means of a process comprising drawing and filming from a mixture of polymers in thermoplastic material, for example in PETG or EVA, composed of transparent neutral material in granules, with a weight concentration ranging from 40% to 95%, to which the photoluminescent plastic masterbatch in granules "A" as described above, is added in a percentage ranging from a minimum of 5% to a maximum of 30 % by weight, and/or the fluorescent plastic masterbatch in granules "B" as described above, in a percentage ranging from a minimum of 5% to a maximum of 30% by weight with respect to the total weight of "C".

As an alternative to compound "C", a plastic compound in granules can be produced, hereinafter referred to as "D", produced by means of a process comprising drawing and filming from a mixture of polymers in thermoplastic material, for example in PETG or EVA, composed of transparent neutral material in granules, in a quantity by weight ranging from 58% to 94.9% with respect to the final weight of the compound, to which the photoluminescent plastic masterbatch in granules "A" as described above, is added in a quantity by weight ranging from a minimum of 5% to a maximum of 30% with respect to the weight of the final composition "D" and inert fluorescent pigments having a size ranging from 2 microns to 10 microns are added, in a quantity by weight ranging from a minimum of 0.1% to a maximum of 12% with respect to the weight of the final compound "D".

As an alternative to compounds "C" and "D", a plastic compound in granules can be produced, hereinafter referred to as "E", produced by means of a process comprising drawing and filming from a mixture of polymers, for example in PETG or EVA, composed of transparent neutral material, in granules, in a quantity by weight ranging from 55% to 94.9% with respect to the weight of the final compound "E", to which the fluorescent plastic masterbatch in granules "B" as described above, is added in a quantity ranging from a minimum of 5% to a maximum of 30% with respect to the weight of the final compound "E" and inert photoluminescent pigments having a size ranging from 5 microns to 65 microns are added, in a quantity by weight ranging from a minimum of 0.1% to a maximum of 15% with respect to the weight of the final compound " E

As an alternative to what is described above for the production of compounds "C", "D" and "E", a plastic compound in granules can be produced, hereinafter referred to as "F", produced, by means of a process comprising drawing and film-forming, from a mixture of polymers, for example in PETG or EVA, composed of transparent neutral material, in granules, in a quantity by weight ranging from 85% to 99.8% with respect to the weight of the final compound "F", to which a mixture is added, composed of inert photoluminescent pigments in powder form having a size ranging from 5 to 65 microns, in a quantity by weight ranging from a minimum of 0.1% to a maximum of 15% with respect to the weight of the final compound "F "and/or inert fluorescent pigments in powder form having a size ranging from 2 microns to 10 microns, in a quantity by weight ranging from a minimum of 0.1% to a maximum of 12% with respect to the weight of the final compound.

The preparation of the powder mixture requires the use of a closed turbomixer equipped with a cooling jacket to avoid the aggregation and consolidation of the pigments due to the increase in temperature by friction. If a gravimetric system with two separate loading inlets is not available, the photoluminescent pigment in powder form, which has a relative density ranging from 3.4 to 3.8, must be poured into the mixer first, then adding the fluorescent pigment, under slow mixing, for a time ranging from 20 minutes to 1 hour, which has a relative density (at 4°C and 1 atm, IUPAC Compendium of Chemical Terminology - the Gold Book Version 2.3.3b) ranging from 1.4 to 1.6.

The steps of the process involving the mixture of photoluminescent and fluorescent pigments are preferably carried out in closed containers and kept at a temperature ranging from lO°C to 20° C.

For the production of the masterbatch (MB) with UV pigments, a machine configuration with two“barref’-shaped worm screws hardened on the surface, is not necessary. Two separate hoppers with gravimetric dosers are necessary, however, for a correct and homogeneous distribution: the first is used for feeding the powdered or pellet resin, the second for dosing the UV pigments into the molten polymer.

For the whole production, it is preferable to keep the degassing active in the last area of the extruder before the die.

A film having a thickness ranging from O.lmm to 4.0mm of polymeric material was therefore produced, for example in PETG or EVA, obtained by filming from the granulated compounds C, D, E and F described above.

The filming must be carried out with an extruder characterized by several thermoregulated zones, equipped with a flat band head adjustable in thickness capable of guaranteeing uniformity of thickness, pull and surface finish.

The temperature of the calender rolls must be adjusted with a temperature controller.

For the extrusion, it is preferable to use a machine with a chamber having suitable dimensions in order to minimize the residence time of the material in the chamber, as, on the one hand, the new photoluminescent inorganic pigments have a high thermal conductivity and, on the other, the temperature of the UV pigments cannot exceed 250°C. Extruders with large internal walls or with complicated screw geometries therefore tend to cause the darkening of final product.

The processing temperature set in the extrusion chamber is preferably about lO°C (50°F) lower than that commonly used for the thermoplastic materials used; also for the surface temperature of the calender rolls, care must be taken to ensure that the film produced is free of "bums".

A filament for a 3D printer with a thickness ranging from 0.175 mm to 0.375 mm in polymeric material, was then produced, for example in PETG, EVA, PMMA, ABS, SBS, PE in various types: HDPE (high-density polyethylene), LDPE (low-density polyethylene), LLDPE (linear low-density polyethylene), PP, PU and PLA, obtained by extrusion from the granulated compounds as for the processes in C, D, E and F described above.

For the extrusion it is preferable to use a machine with a chamber having suitable dimensions in order to minimize the residence time of the material in the chamber, as, on the one hand, the new photoluminescent inorganic pigments have a high thermal conductivity and, on the other, the operating temperature of the UV pigments cannot exceed 250°C.

Extruders with large internal walls or with complicated screw geometries therefore tend to cause the darkening of final product.

The processing temperature set in the extrusion chamber is preferably about l0°C (50°F) lower than that commonly used for the thermoplastic materials used; also for the surface temperature of the calender rolls, care must be taken to ensure that the film produced is free of "burns".

The following biocompatible class I resins (Directive 93/42/EEC) were also produced, to be used in the 3D printing of dental appliances such as aligners and bites. A first biocompatible photopolymer resin "Rl" was formed, produced with monomers and/or with polymers of acrylic esters that can be activated with UV light with a wavelength ranging from 315 nm to 400 nm, containing inert photoluminescent pigments (crystals) having a size ranging from 5 to 65 microns, with a weight concentration ranging from a minimum of 2% to a maximum of 25% with respect to the total weight of the resin. Pigments of the series G9, G8, B8 and A9 produced by Allureglow® USA, LLC, California (USA) were used. These photoluminescent pigments have characteristics of high efficiency and durability both in the "glow" and "afterglow" phases, a high operating temperature, a more than high disintegration temperature and a high anchoring capacity with the base polymers in liquid form.

A second biocompatible photopolymer resin "R2" was also formed, produced with monomers and/or with polymers of acrylic esters which can be activated with a UV light having a wavelength ranging from 315 nm to 400 nm, containing inert fluorescent pigments (crystals) having a size ranging from 2 to 10 microns, with a weight concentration ranging from a minimum of 0.5% to a maximum of 20% with respect to the total weight of the resin. As an example, pigments were used, consisting of rare earth oxides with coloured luminescence activated by long-wave UV rays such as aluminium barium magnesium oxide (CAS Nr. 63774-55-0), Al₂Ce₂Mg₂0iiTb₂ (CAS Nr. 67542-72- 7), yttrium oxide vanadium phosphate doped with europium and dysprosium (CAS Nr. 100403-11- 0), B₄Sr0₇ doped with europium (CAS Nr. 71786-49-7), yttrium doped with europium (CAS Nr. 68585 -82-0), calcium fluoride chloride phosphate (CAS Nr. 75535-31-8) and di-zinc orthosilicate doped with manganese (CAS Nr. 68611-47- 2). These fluorescent pigments have characteristics of high efficiency, a high operating and disintegration temperature and a high anchoring capacity with base polymers in liquid form.

Experimental procedure

The production feasibility was verified, via PETG-based masterbatch compounds containing photoluminescent pigments, and the possibility of their use in the filming of sheets destined for thermoforming.

In the production of the masterbatches and in the subsequent filming tests, Polyethylene terephthalate - Glycol (PETG) was used: SKYGREEN® S2008, manufacturer SK Chemicals, having a specific weight of 1.27 (ASTMD792), water absorption after 14 hours in immersion 0.13% (ASTM D570), initial water content 0.04% by weight/weight of the material, moulding shrinkage parallel to flow (ASTM 955) ranging from 0.3 to 0.6%, Rockwell hardness (ASTM D785) 110 (R scale). The pigments used are photoluminescent ALLUREGLOW® with yellow-green luminescence and a particle size of 10-25 microns, white fluorescent EU₂0₃ ALLUREGLOW® activator with white-blue luminescence under UV light and particle size <5 microns.

Gravimetric dosers were used for the dosage of the polymer and pigments, which ensured a precise and constant flow-rate during the conductive process.

Prior to the production of the masterbatch, the dosability of the pigments was verified within the range foreseen by the formulation. The flow-rate of the material was found to be correct and stable, and no particular problems were encountered during the dosage phase (such as formations of agglomerates, clogging, "bridges", adhesion to the walls of the doser).

A Leistritz LSZ 27 HP co-rotating twin-screw extruder was used for the production of the masterbatch, characterized by a ratio of a screw having a diameter of 27 mm and an L/D ratio of 40. The polymer and pigments were fed through Brabender gravimetric dosers having the following technical characteristics: distance between the axes of the screws: 23 mm; screw diameter: 27 mm; screw length: 40 D; drive: DC motor; drive power: 32 KW; number of thermoregulation areas: 10; thermal power: 9 KW; number of cooling areas: 9; cooling of feeding area: water; cooling water consumption - feeding area: 30 l/h.

For the compounding process, the polymer and pigments were fed into the first area of the extruder, using gravimetric dosing devices.

The process parameters used are indicated below. For the whole duration of the test, the degassing was kept active in the last area of the extruder before the die (area 9). A temperature gradient was used ranging from 260°C in the initial part (area 1) to 250°C in the final part of the extruder (area 9), die temperature = 254°C. The screw rate was 200 rpm, the torque was 42/47% and the temperature was 26l°C.

The composition of the masterbatch (PETG001) was as follows: PETG

74.8%, photoluminescent pigment ALLUREGLOW® 24.9%, fluorescent pigment ALLUREGLOW® 0.249%, wherein all the percentages are by weight/total weight of the composition.

Approximately 8.5 kg of PETG001 masterbatch were produced.

The presence of the desired photoluminescence effect in the granules of the masterbatch thus obtained was verified.

The film was produced with a BG Plast extruder 30/30 L/D, characterized by 6 thermoregulated areas, equipped with a flat 20 mm band head with 3 thermoregulated areas. A Dr Collin calender (Chill Roll) is positioned downstream of the extruder, capable of guaranteeing uniformity of thickness, pull and surface finish. The temperature of the calender rolls is regulated by a Piovan thermoregulator.

Three different PETG dry mixtures (dryblends) were produced, indicated as PETG002, PETG003 and PETG004 respectively, with the addition of the masterbatch PETG001, at three different concentrations as indicated below (in weight/total weight of the mixture):

PETG002: masterbatch PETG001 10%, PETG SKYGREEN 90%;

PETG003: masterbatch PETG001 15%, PETG SKYGREEN 85%;

PETG004: masterbatch PETG001 10%, PETG SKYGREEN 90%.

The identification of the parameters suitable for the PETG filming required a series of preliminary tests; once the most suitable conditions had been defined, the process took place regularly, allowing a sheet having a good overall quality to be obtained.

The process parameters used in the filming were the following: temperature from 245 to 240°C, screw rate 30 rpm, torque 5.8 Nm, melt temperature 225°C. Extruder parameters: primary pull 0.6 m/min, secondary pull 11%, head opening 500 microns, roll temperature 60°C. A few meters of film having a thickness of approximately 500 microns were produced for each composition.

Starting from the films produced, 20 square-shaped samples (120 mm x 120 mm) were obtained with a manual cutter for each film composition.

Migration tests

Migration tests of some elements were carried out on appliances obtained according to the present invention, sought by ICP-Plasma spectrometer, according to the standard EN 71-3: 2013 + A3: 2018 - Category III: Scraped off at the independent certification body IISG Srl of Cabiate (Como, Italy). The following results were obtained:

All the samples were analyzed, also for the identification of antimony, arsenic, barium, boron, cadmium, chromium, zinc, cobalt, copper, lead, manganese, mercury, tin, selenium and nickel. The concentration of each of the elements listed above is lower than the detection limit of the method for all the samples.

The results obtained show that the compositions of the invention do not release significant amounts of elements that are potentially harmful to health.

Claims

1. A material for producing a dental appliance comprising a mixture (M) of:

1. at least one biocompatible polymer; and at least one of:

ii. a photoluminescent substance which is an inorganic crystal having a particle size (D50) ranging from 5 to 65 micrometers;

iii. a fluorescent substance which is an inorganic crystal having a particle size (D50) ranging from 2 to 10 micrometers.

2. The material for producing a dental appliance according to claim 1, wherein the mixture (M) comprises components i. and ii. or components i. and iii. or components i., ii., and iii. and wherein said material is in the form of a sheet or a film for preparing a removable template for orthodontic or aesthetic purposes, a filament or a resin for 3D-printing or a disk for CAD/CAM machines.

3. The material according to one of the previous claims, wherein the polymer i. in the mixture (M) is at least one of glycol-modified polyethylene terephthalate (PETG), ethylene vinyl acetate (EVA), polymethylmethacrylate (PMMA), a styrene/butadiene copolymer (SBS), at least one type of polyethylene (PE) selected from HDPE (high-density polyethylene,), LDPE (low-density polyethylene), LLDPE (linear low-density polyethylene), polypropylene (PP), a polyurethane (PU), polystyrene crystal (GPPS), polylactic acid, a polyacrylate cross-linkable with UV light having a wavelength ranging from 315 from 400 nm, and their mixtures and copolymers.

4. The material according to at least one of the previous claims, wherein the photoluminescent substance ii. in the mixture (M) is selected from photoluminescent pigments consisting of, or comprising, strontium aluminate oxides.

5. The material according to at least one of the previous claims, wherein the fluorescent substance iii. in the mixture (M) is selected from non-metal salts, such as fluorescent phosphorous salts (phosphates), for example amblygonite, anapaite, arctite, autunite, bergenite, foggite, furongite, herderite, nacapaite, apatites, including, without limitation, hydroxyapatite (medium fluorescence), fluorapatite and strontium-apatite (high fluorescence) and the like, and pigments consisting of rare earth oxides with coloured luminescence activated by long-wave UV rays such as aluminium barium magnesium oxide (CAS Nr. 63774-55-0), Al₂Ce₂Mg₂0iiTb₂ (CAS Nr. 67542-72-7), vanadium phosphate yttrium oxide doped with europium and dysprosium (CAS Nr. 100403-11-0), B₄Sr0₇ doped with europium (CAS Nr. 71786-49-7), yttrium oxide doped with europium (CAS Nr. 68585-82-0), calcium fluoride chloride phosphate (CAS Nr. 75535-31-8) and di-zinc orthosilicate doped with manganese (CAS Nr. 68611-47-2).

6. The material according to at least one of the previous claims, wherein, in the mixture (M), the photoluminescent inorganic crystals have a particle size (D50) within the range of 20 to 60 micrometers, preferably from 30 to 50 micrometers and/or the fluorescent inorganic crystals have a particle size (D50) within the range of 2.5 to 6 micrometers, preferably from 3 to 5 micrometers.

7. The material according to one of the previous claims, wherein, with respect to the total weight of the mixture (M), the content of the photoluminescent substance ii. ranges from 0.1 to 15% by weight and/or the content of the fluorescent substance iii. ranges from 0.1 to 12% by weight.

8. A method for the production of a dental appliance comprising the material according to any of the previous claims, said method comprising a step of forming the appliance, or at least a part thereof, in the definitive form or as an intermediate, via a 3D-printing technique and, optionally, a post-processing step of the appliance, or part thereof, obtained via 3D-printing.

9. A dental appliance, movable or fixed, suitable for being applied in the oral cavity, or on part of the oral cavity, preferably on the teeth or on part of the teeth of a subject, for therapeutic purposes or for the prevention of a disease or a disorder or for non-therapeutic purposes, comprising the material according to one of claims 1-7.

10. The dental appliance according to claim 9 in the form of an occlusal plate, template, orthodontic appliance or dental prosthesis.

11. A non-therapeutic method for improving the aesthetic characteristics of a subject’s teeth comprising the application of a dental appliance comprising the material according to any of claims 1-7.

12. A photosensitive substance for use in the treatment of a disease or disorder of the oral cavity, preferably the teeth, wherein said treatment comprises photodynamic therapy (PDT) wherein energy is supplied to said photosensitive substance for the formation of active species deriving from oxygen, wherein the dental appliance comprising the material according to any of claims 1-6 is used as a light source for supplying, at least partially, the energy for the activation of the photosensitive substance.

13. A mixture (M) comprising:

i. at least one biocompatible thermoplastic polymer; and at least one of:

11. a photoluminescent substance;

iii. a fluorescent substance,

wherein:

- the thermoplastic polymer i. is at least one of glycol-modified polyethylene terephthalate (PETG), ethylene vinyl acetate (EVA), polymethylmethacrylate (PMMA), a styrene/butadiene copolymer (SBS), polyethylene (PE) in a typology selected from: HDPE (high-density polyethylene), LDPE (low-density polyethylene), LLDPE (linear low-density polyethylene), polypropylene (PP), a polyurethane (PET), polystyrene crystal (GPPS), polylactic acid, a polyacrylate activatable with UV light with a wavelength ranging from 315 to 400 nm and their mixtures or copolymers;

- the photoluminescent substance ii. is an inorganic crystal having a particle size (D50) ranging from 5 to 65 micrometers, preferably selected from photoluminescent pigments consisting of, or comprising, strontium aluminate oxides;

- the fluorescent substance iii. is an inorganic crystal having a particle size (D50) ranging from 2 to 10 micrometers, selected from non-metal, fluorescent salts such as: abrigonite, anapaite, arctite, autunite, bergenite, foggite, furongite, herderite, nacapaite, apatites, including, without limitation, hydroxyapatite (medium fluorescence), fluorapatite and strontium-apatite (high fluorescence) and the like, and pigments consisting of rare-earth oxides with coloured luminescence activated by long-wave UV rays such as aluminium barium magnesium oxide (CAS Nr. 63774-55-0), Al₂Ce₂Mg₂0iiTb₂ (CAS Nr. 67542-72-7), vanadium phosphate yttrium oxide doped with europium and dysprosium (CAS Nr. 100403- 11-0), B₄Sr0₇ doped with europium (CAS Nr. 71786-49-7), yttrium oxide doped with europium (CAS Nr. 68585-82 -0), calcium fluoride chloride phosphate (CAS Nr. 75535-31-8) and di-zinc orthosilicate doped with manganese (CAS Nr. 68611- 47-2).