Functionalized biomimetic hydroxyapatite

Abstract

The present invention relates to a carbonate-hydroxyapatite functionalized with a bactericide selected from chlorhexidine and its salts, benzalkonium halides, diisobutylphenoxyethoxyethyldimethylbenzylammonium halides, alkyldimethylethylbenzylammonium halides, cetylpyridinium halides, and mixtures thereof.The present invention also relates to a cosmetic composition, such as an oral care composition or a skin care composition, comprising said functionalized carbonate-hydroxyapatite.

Description

[Technical Field]

[0001] Technical field The present invention relates to carbonate-hydroxyapatite functionalized with a bactericide selected from chlorhexidine and its salts, benzalkonium halide, diisobutylphenoxyethoxyethyldimethylbenzylammonium halide, alkyldimethylethylbenzylammonium halide, cetylpyridinium halide, and mixtures thereof. The present invention also relates to cosmetic compositions, such as oral care compositions or skincare compositions, that contain the functionalized carbonate-hydroxyapatite. [Background technology]

[0002] Background technology Hydroxyapatite, Ca 10 (PO4)6(OH)2 is a compound found in the human body and is a major mineral component of bone tissue and enamel. In fact, 99% of the calcium in the human body is stored in bone tissue in the form of hydroxyapatite. Thanks to its excellent biocompatibility, synthetic hydroxyapatite is used in artificial bones, artificial tooth roots, bone grafts, and pharmaceutical carriers. More recently, synthetic hydroxyapatite has also been applied to cosmetics, such as toothpaste and sunscreens.

[0003] In oral care, for example, hydroxyapatite is currently used as a remineralizer material in toothpaste, chewing gum, and in post-treatment for teeth whitening; as a filler material in compound polymer materials in the preparation of dental pieces; providing long-term tooth remineralization.

[0004] Recently, hydroxyapatite has been proposed as a carrier for antimicrobial agents such as metal ions or quaternary ammonium salts, and for other germicidal actives. EP 0 539 651 discloses a toothpaste (toothpaste paste or toothpaste powder) containing a calcium compound such as hydroxyapatite and an antibacterial metal ion supported by the calcium compound. Preferred metals are silver, zinc, and copper.

[0005] KR 2004 / 0081936 relates to a toothpaste composition containing 0.01 to 5% by weight of cetylpyridinium chloride based on the total weight of the composition, wherein the cetylpyridinium chloride in the composition is coated on the surface of granules selected from the group consisting of precipitated calcium carbonate, silica, zeolite, colloidal silicon dioxide, and anhydrous calcium silicate. The coating was obtained by using a fluidized bed granulator or by immersion method.

[0006] Carlos A. Soriano deSouza et al. evaluated the adsorption of chlorhexidine on synthetic hydroxyapatite (HA) and its antimicrobial activity in Colloids Surf. B, 87(2), 310-318 (2011). They demonstrated that the binding of chlorhexidine to HA did not affect its antimicrobial activity against the growth of Enterococcus faecalis and reduced bacterial adhesion.

[0007] EP 3 484 435 relates to an oral care composition containing composite particles, wherein the particles are as follows: - Formula Ca n (X) x (AO y ) z A water-insoluble inorganic component having the following properties, where: X is selected from OH, F, and Cl; A is selected from C, P, Si, and combinations thereof; n=1 to 5; x=0 or 1; y=3 or 4; z=1 to 3; - and cationic bactericides It contains, where the particles are formed into flakes and have a thickness of 15-80 nm. Hydroxyapatite is a preferred water-insoluble inorganic component, and chlorhexidine and cetylpyridinium chloride are preferred cationic bactericides.

[0008] Okada M. et al. (Dent. Mater. J. 35(4), 651-658 (2016)) evaluated the adsorption / desorption behavior of cetylpyridinium chloride (CPC) onto HAp nanoparticles of various forms (spherical, short rod-shaped, long rod-shaped, and fibrous) in order to develop an enamel repair agent using nanoparticles with antibacterial properties.

[0009] However, there remains a need in the art to provide a carrier that can gradually release bactericidal substances in response to specific conditions, thereby ensuring a constant and controlled preservative effect over time, and thus guaranteeing long-term protective activity.

[0010] We were surprised to find that carbonate-hydroxyapatite (C-HAp) functionalized with specific fungicides exhibits favorable characteristics in the reaction kinetics of the release of the incorporated fungicide: when the fungicide is incorporated after the formation of C-Hap particles, its release is slower and more controlled, while when the fungicide is incorporated during the formation of C-Hap particles, it is released more readily in response to pH changes. As a result, depending on the required release application and reaction kinetics, it is possible to select a more suitable synthesis for the substituted C-Hap, thus yielding products with either delayed or rapid release, respectively.

[0011] Furthermore, compared to unfunctionalized hydroxyapatite, the functionalized C-Hap of the present invention exhibits a more uniform particle structure, forming spherical microaggregates. For oral care applications in particular, a material with a uniform surface is preferable because it improves biocompatibility, adhesion (contact), and substance exchange with natural tissues, thereby increasing remineralization activity.

[0012] In addition, calcium ions may be partially substituted with other metal cations such as zinc, copper, and silver, increasing the bactericidal substance release and antibacterial activity of the functionalized C-Hap of the present invention.

[0013] Carbonate hydroxyapatite is a hydroxyapatite in which a hydroxyl anion or phosphate anion is substituted with a carbonate anion. Carbonate hydroxyapatite can be successfully synthesized by carefully selecting the operating conditions (temperature, concentration, etc.) and reagents. Synthetic C-Hap more closely mimics the composition, structure, dimensions, and morphology of bone apatite crystals than pure synthetic Hap, and for these reasons, it is also defined as a "biomimic" hydroxyapatite.

[0014] To the best of the applicant's knowledge, no one has previously described the functionalized C-Hap of this disclosure and their advantageous properties. In the present invention, the definition of "carbonate-hydroxyapatite functionalized with a fungicide" means that the fungicide is either "adsorbed on" C-Hap or (partially) "incorporated into" the structure of C-Hap, depending on the production process. [Overview of the Initiative]

[0015] Description of the present invention Therefore, the object of the present invention is a functionalized C-Hap (C-Hap) containing 0.3 to 20 wt% of carbonate, which is functionalized with a bactericide ranging from 0.01 to 10 wt% based on the total weight of the functionalized C-Hap, wherein the bactericide is selected from chlorhexidine and its salts, benzalkonium halides, diisobutylphenoxyethoxyethyldimethylbenzylammonium halides, alkyldimethylethylbenzylammonium halides, cetylpyridinium halides, and mixtures thereof.

[0016] Another objective of the present invention is to provide cosmetic compositions containing the functionalized C-HaP in an amount ranging from 0.05 to 35 wt%.

[0017] A process for the preparation of said functionalized carbonate-hydroxyapatite is a further object of the present invention, the process comprising the following steps: i) providing an aqueous solution or suspension comprising a Ca cation source (and optionally, a source of metal cations substituting calcium); ii) mixing the aqueous solution or suspension of step i. with an aqueous solution or suspension comprising a phosphate source; iii) stirring the mixture thus obtained in the presence of carbon dioxide or carbonate, to allow the formation of a suspension of C-HAp particles wherein the bactericide is selected from chlorhexidine and salts thereof, benzalkonium halides, diisobutylphenoxyethoxyethyl dimethylbenzylammonium halides, alkyldimethylethylbenzylammonium halides, cetylpyridinium halides, and mixtures thereof, and is added to the solution / suspension of steps i. to iii. or is adsorbed onto previously prepared C-HAp particles. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Brief Description of the Drawings [Figure 1] Fig. 1. X-ray diffraction spectrum of the functionalized C-HAP of Example 1. [Figure 2] Fig. 2. SEM image of C-Hap. [Figure 3] Fig. 3. SEM image of the functionalized C-Hap of Example 1. MODES FOR CARRYING OUT THE INVENTION

[0019] Detailed Description of the Invention Preferably, the functionalized carbonate-hydroxyapatite of the present invention is functionalized with 0.05 to 5 wt% of the bactericide, based on the total weight of the functionalized C-Hap. Based on the total weight of the functionalized C-HAp, the carbonate content in the functionalized C-HAP according to the present invention can range from 0.3 to 20 wt%, preferably from 1.0 to 12 wt%. Carbonate anions can occupy two different sites in the C-HAp structure: that is, it can partially replace OH - anions (site A) and / or phosphate anions (site B). According to the present invention, the carbonate ions are preferably at site B.

[0020] The carbonate-hydroxyapatite of the present invention is represented by the following formula I: Ca (10-x) M x (PO4) (6-2 / 3y) (CO3) y (OH)2I wherein: M is a metal cation selected from the group consisting of cations of Cu, Mg, Al, Zn, Co, Fe, Ag, Mn, Sr, and Ti, or a combination of such cations; x is between 0 and 2.5, preferably between 0.05 and 2.5, more preferably between 0.1 and 2; y is between 0.1 and 3, preferably between 0.2 and 1.5.

[0021] In a preferred embodiment of the present invention, x in formula I is zero, and the carbonated hydroxyapatite does not contain metal cations that replace calcium. This carbonate-hydroxyapatite is represented by the following formula II: Ca 10 (PO4) (6-2 / 3y) (CO3) y (OH)2II wherein y can have the same values as described above. In another preferred embodiment, x in formula I is between 0.05 and 2.5, more preferably between 0.1 and 2.

[0022] Various metal cations with antibacterial activity can be incorporated into the C-HAp structure and partially substitute for calcium cations. Examples of these metal cations include copper (Cu 2+ ), aluminum (Al 3+ ), magnesium (Mg 2+ ), zinc (Zn 2+ ), cobalt (Co 2+ ), iron (Fe 3+ and Fe 2+ ), silver (Ag + ), manganese (Mn 2+ ), strontium (Sr 2+ ), Titanium (Ti 4+ ), or a combination thereof.

[0023] In a preferred embodiment of the present invention, metal-substituted C-HAp contains cations selected from among Cu, Zn, Ag, and combinations thereof. In a more preferred embodiment, the metal-substituted C-HAp contains Zn or Cu cations, or a combination thereof. Most preferably, the metal-substituted C-HAp contains a Cu cation. Preferably, the fungicide is selected from chlorhexidine and its salts, benzalkonium halide, cetylpyridinium halide, and mixtures thereof. More preferably, the fungicide is cetylpyridinium halide. Cetylpyridinium chloride (CPC) is a preferred cetylpyridinium halide.

[0024] According to a preferred embodiment of the present invention, the functionalized C-HAP has a degree of crystallinity between 15% and 85%, preferably between 15% and 70%. The degree of crystallinity is given by the following equation: %crystallization=100·(C / (A+C)) It can be calculated according to the formula, where C and A are the sum of the areas of sharp peaks and the sum of the areas of amorphous peaks, respectively (this is the area between the sharp peaks and the background in the X-ray diffraction spectrum; see Figure 1).

[0025] Preferably, the functionalized C-HAp of the present invention is in the form of particles smaller than 5 μm, preferably between 0.01 μm and 0.5 μm in size. Typically, the C-HAp particles are bound together to form aggregates of particles (clusters). These aggregates may have microscopic dimensions, with sizes ranging from 0.1 μm to 50 μm, more specifically between 0.5 μm and 25 μm.

[0026] The functionalized carbonate-hydroxyapatite of the present invention can be prepared by adding a bactericide as a reagent in the process for preparing C-Hap particles, or by adsorbing the bactericide onto previously prepared C-Hap particles.

[0027] Processes for preparing carbonate-hydroxyapatite are well known in the art. Typically, C-HAp is obtained by contacting a source of calcium cations with a source of phosphate anions in the presence of a source of carbon dioxide or carbonate anions.

[0028] According to aspects of the present invention, the process for preparing the functionalized carbonate-hydroxyapatite of the present invention is as follows: i) Provide an aqueous solution or suspension containing a Ca cation source (and optionally, a source of a metal cation that replaces calcium); ii) Mix the aqueous solution or suspension from step i) with the aqueous solution or suspension containing the phosphate source; iii) Allow the formation of a suspension of C-HAp particles by stirring the mixture in the presence of carbon dioxide or a carbonate. The bactericide is selected from chlorhexidine and its salts, benzalkonium halide, diisobutylphenoxyethoxyethyldimethylbenzylammonium halide, alkyldimethylethylbenzylammonium halide, cetylpyridinium halide, and mixtures thereof, and is added to the solution / suspension of steps i) to iii).

[0029] Suitable sources of calcium cations are calcium fluoride, calcium chloride, calcium nitrate, calcium carbonate, calcium hydroxide, calcium acetate, or a combination thereof. Preferably, the source of calcium cations is calcium hydroxide or calcium chloride. More preferably, the source of calcium cations is calcium hydroxide.

[0030] In the process for preparing functionalized C-HAP, the concentration of calcium cations in the aqueous solution or suspension in step i) may be from 0.15 mol / l to 10 mol / l, preferably from 0.5 mol / l to 5 mol / l. According to a preferred embodiment of the process of the present invention, the aqueous solution or suspension of step i) may further contain a source of metal cations, which are selected from or combinations of cations of Cu, Mg, Al, Zn, Co, Fe, Ag, Mn, Sr, and Ti. Preferred sources are oxides or salts of these cations, or mixtures thereof.

[0031] Suitable sources of zinc cations are zinc acetate, zinc nitrate, zinc citrate, zinc fluoride, zinc chloride, zinc hydroxide, zinc carbonate, or combinations thereof. Preferably, the source of zinc cations is zinc carbonate. In the process for preparing functionalized Zn-substituted C-HAP, the zinc cation concentration may range from 0.01 mol / l to 5 mol / l, preferably from 0.1 mol / l to 1.5 mol / l.

[0032] Suitable sources of copper cations are copper acetate, copper nitrate, copper citrate, copper sulfate, copper chloride, copper hydroxide, copper carbonate, or combinations thereof. A preferred source of copper cations is copper chloride. In the process for preparing functionalized Cu-substituted C-HAP, the concentration of copper cations may range from 0.01 mol / l to 5 mol / l, preferably from 0.1 mol / l to 1.5 mol / l.

[0033] Suitable sources of silver cations are silver oxide, silver nitrate, silver acetate, silver sulfate, silver benzoate, silver salicylate, silver carbonate, silver citrate, or silver phosphate. In the process for preparing functionalized Ag-substituted C-HAP, the concentration of silver cations may range from 0.01 mol / l to 5 mol / l, preferably from 0.1 mol / l to 1.5 mol / l. Suitable sources of aluminum cations are aluminum chloride, aluminum hydrochloride, aluminum sulfate, aluminum nitrate, or mixtures thereof. Preferably, the source of aluminum cations is aluminum chloride.

[0034] In the aqueous solution or suspension of step i), aluminum cations may be present at concentrations from 0.02 mol / l to 5.0 mol / l, preferably from 0.1 mol / l to 3.0 mol / l. Suitable sources of magnesium cations are magnesium hydrogen phosphate, trimagnesium phosphate, magnesium dihydrogen phosphate, magnesium chloride, magnesium chloride hexahydrate, magnesium glycerophosphate, magnesium hydroxide, heavy magnesium carbonate, magnesium oxide, magnesium citrate, magnesium silicate, or mixtures thereof. Preferably, the source of magnesium cations is magnesium chloride hexahydrate.

[0035] In the process for preparing functionalized Mg-substituted C-HAp, magnesium cations may be used at an initial concentration ranging from 0.005 mol / l to 3.0 mol / l, preferably from 0.05 mol / l to 1.0 mol / l. Preferably, the aqueous solution or suspension of step i) has a pH between 7 and 13, more preferably between 8 and 12. Suitable sources of phosphate anions are disodium hydrogen phosphate, sodium dihydrogen phosphate, orthophosphate, dipotassium hydrogen phosphate, potassium dihydrogen phosphate, diammonium hydrogen phosphate, or a combination thereof. Preferably, the source of the phosphate anion is orthophosphate.

[0036] In the process for preparing functionalized C-HAp, the concentration of the phosphate anion in the aqueous solution or suspension of step ii) may range from 0.05 mol / l to 10 mol / l, preferably from 0.5 mol / l to 5 mol / l. Step ii) may be carried out over a period of time between 30 minutes and 2 hours at a temperature below 60°C, preferably between 30°C and 50°C.

[0037] In the process of the present invention, step iii) can develop the functionalized carbonate-hydroxyapatite particles to a desired size and structure. Typically, step iii) is carried out at a temperature below 60°C for at least 6 hours. Preferably, step iii) is carried out at a temperature between 25°C and 45°C for 6 to 36 hours, more preferably 12 to 24 hours. Favourite substitution with carbonate may be advantageously achieved by simply stirring the solution or suspension in the presence of carbon dioxide gas, for example, using a mechanical stirrer, or by passing carbon dioxide gas through the liquid phase or by combining mechanical stirring with gas aeration.

[0038] Carbon dioxide gas may also be a gas containing carbon dioxide. Pure carbon dioxide gas or air may be used as carbon dioxide gas. Alternatively, the carbonate may be added beforehand to the aqueous solution or suspension of step i), or to the solution or suspension containing the phosphate source. Otherwise, the carbonate may be added to the mixture obtained in step ii).

[0039] Furthermore, step ii) may be carried out by simultaneously adding a solution or suspension containing a carbonate and another solution or suspension containing a phosphate anion to the aqueous solution or suspension of step i). Ammonium carbonate, sodium bicarbonate, sodium carbonate, potassium carbonate, or potassium bicarbonate may be used as carbonates. Alternatively, in the case of metal-substituted C-Hap, the carbonate source may be the carbonate of the substituted metal.

[0040] The carbonate concentration can range, for example, from 0.01 mol / l to 3.0 mol / l. Similarly, the fungicide may be added to the solution or suspension in steps i) and ii), or to the mixture in step iii), or as a separate solution in step ii). Preferably, the fungicide is added to the mixture at the beginning of step iii). The concentration of the disinfectant can range, for example, from 0.001 mol / l to 1.0 mol / l.

[0041] In an embodiment of the present invention, the process for preparing functionalized C-Hap is as follows: iv) Separating the functionalized carbonate-hydroxyapatite particles from the suspension obtained from step iii); v) and drying the wet particles It also includes.

[0042] The separation in step iv) is carried out using techniques well known to those skilled in the art, such as decantation, centrifugation, filtration, spray drying, etc. In step v), the powder is dried, for example, by freeze-drying or drying in a ventilated oven or vacuum oven at 40-90°C to reduce the particle size distribution to one suitable for the desired use.

[0043] In a preferred embodiment, the process may also include an additional step of washing the separated particles with water or a basic solution prior to drying step v). The washing operation may be repeated several times if desired. Advantageously, any washing step is useful for removing any reagent residue that may have been adsorbed or captured by particle aggregates.

[0044] In a further embodiment, the functionalized C-HAp of the present invention may be prepared by functionalizing C-Hap particles that are optionally metal-substituted and prepared according to the process described above, but without the addition of any fungicide. These C-Hap particles may be functionalized by adsorption from a concentrated solution of a fungicide, for example, as described in Okada M. et al., Dent. Mater. J. 35(4), 651-658 (2016). The C-Hap of the present invention, functionalized with a bactericide, can be used for the preparation of cosmetic compositions containing the functionalized carbonate-hydroxyapatite in amounts ranging from 0.05 wt% to 35 wt%, preferably from 0.5 wt% to 25 wt%.

[0045] Preferred cosmetic compositions are oral care compositions or skin care compositions. Examples of skincare compositions include hand sanitizers, foot lotions, deodorants, and lipsticks. Examples of oral care compositions include toothpaste, tooth powders, chewing gum for oral and dental hygiene, mouthwash, and mouthbath concentrates and gargles.

[0046] example Example 1 45 ml of deionized water containing 0.013 moles of H3PO4 and 0.0022 moles of cetylpyridinium chloride monohydrate were added dropwise to 50 ml of deionized water containing 0.2 moles of Ca(OH)2 and 0.015 moles of CaCO3 at 37°C, while stirring. Phosphate solution was added over a period of approximately 60 minutes. The resulting suspension was maintained at a temperature of 37°C for 24 hours while being stirred. Functionalized C-Hap particles were recovered by centrifugation (at 6000 revolutions per minute for 20 minutes) and washed three times with deionized water. At the end of the preparation process, the functionalized C-Hap particles were dried in an oven under vacuum at 80°C.

[0047] Example 2 30 ml of deionized water containing 0.013 moles of H3PO4 was added dropwise to 50 ml of deionized water containing 0.2 moles of Ca(OH)2 and 0.015 moles of CaCO3 at 37°C, while stirring. Phosphate solution was then added over a period of approximately 60 minutes. At the end of the addition, 15 ml of deionized water containing 0.0022 mol of cetylpyridinium chloride monohydrate was added dropwise to the reaction mass while stirring. The resulting suspension was then maintained at a temperature of 37°C for 24 hours with gentle stirring. Functionalized C-Hap particles were recovered by centrifugation (at 6000 rpm for 20 minutes) and washed three times with deionized water. At the end of the preparation process, the functionalized C-Hap particles were dried in an oven under vacuum at 80°C.

[0048] Example 3 30 ml of deionized water containing 0.013 moles of H3PO4 was added dropwise, while stirring, to 50 ml of deionized water containing 0.18 moles of Ca(OH)2, 0.02 moles of copper sulfate, and 0.02 moles of Na2CO3 at 37°C. The phosphoric acid solution was then added over a period of approximately 60 minutes. 15 ml of deionized water containing 0.0022 moles of cetylpyridinium chloride monohydrate was added dropwise to the reaction product while stirring, and the preparation was continued. The resulting suspension was then maintained at a temperature of 37°C for 24 hours with gentle stirring. Functionalized Cu-substituted C-Hap particles were recovered by centrifugation (6000 rpm for 20 minutes) and washed three times with deionized water. At the end of the preparation process, the functionalized Cu-substituted C-Hap particles were dried in an oven under vacuum at 80°C.

[0049] Table 1 reports the CPC levels in the functionalized C-HAp of Examples 1-3. Table 1. [Table 1]

[0050] The concentration of CPC in functionalized C-Hap was determined by UV-Vis spectrophotometric analysis according to the European Pharmacopoeia. In short, the amount of CPC in the solution was determined by dissolving 1 mg of functionalized C-Hap in 1 ml of 0.1 M HCl and reading the absorbance at 259 nm.

[0051] Characterization by X-ray diffraction The C-HAP functionalized with CPC in Example 1 was dried and characterized using a MiniFlex X-ray diffractometer (Rigaku) ​​with the following settings: - Voltage: 30kV - Current: 15mA - Radiation type: Cu - Radiation wavelength: 1.54056Å - 2θ range: 10° to 60° in 0.02° steps - Scanning speed: 2°(2θ) / min

[0052] The diffraction spectrum (Figure 1) shows typical peaks for hydroxyapatite, as reported in the literature (standard hydroxyapatite stored in the ICDD diffraction data database; File n. 01-086-1199). However, the sample is poorly crystalline; the large diffraction (diffusion) peaks detected are due to the low crystallinity and are induced by the synthesis conditions. The crystallinity of the functionalized C-HAP in Example 1 is 30±5%.

[0053] Characterization using scanning electron microscopy Functionalized C-Hap was further characterized using scanning electron microscopy (SEM). SEM imaging highlighted that, compared to carbonate-hydroxyapatite (Figure 2), Example 1's CPC-functionalized C-Hap (Figure 3) exhibited a more uniform particle organization, forming spherical microaggregates in suspension. This behavior allows for the creation of regular exchange surfaces of the composite responsible for the controlled release of cetylpyridinium chloride, along with lower crystallinity and higher reactivity.

[0054] Release of cetylpyridinium chloride The time-dependent release of CPC from functionalized C-Hap was evaluated by placing 150 mg of functionalized C-Hap particles into two 5 ml buffer solutions at different pH levels. The variability of CPC concentration in the buffer solutions was determined by UV-Vis spectrophotometry. The results are reported in Table 2.

[0055] Table 2 [Table 2]

[0056] The results summarized in Table 2 show that the functionalized C-Hap obtained according to Example 1 and Example 2 releases CPC over time in a pH-dependent manner. Indeed, lower pH levels (from 6.3 to 5.5) promote the release of CPC from C-Hap, thus leading to a more rapid achievement of the active concentration of cetylpyridinium chloride at the application site (as early as 30 minutes later). When used in skincare and personal care cosmetic products, such as deodorants, hand sanitizers, foot lotions, lipsticks, etc., functionalized C-Hap can release CPC more rapidly due to the skin's pH (approximately 5.5), thus enabling effective yet long-lasting protection of the skin against microorganisms.

[0057] When applied to areas with a higher pH, such as the mouth, through oral care products, CPC is released slowly. Functionalized C-Hap has time to adhere to the enamel surface, preventing the formation of biofilms that make up plaque. The decrease in oral mucosal pH after meals (due to food consumption) allows for increased CPC release, which is advantageous in that it can reduce the microbial population responsible for plaque formation.

Claims

1. Functionalized carbonate-hydroxyapatite (C-Hap), which is functionalized with fungicides ranging from 0.01% by weight (wt%) to 10 wt%, and contains 0.3 wt% to 20 wt% carbonate, based on the total weight of the functionalized C-Hap. Here, the disinfectant is selected from chlorhexidine and its salts, benzalkonium halide, diisobutylphenoxyethoxyethyldimethylbenzylammonium halide, alkyldimethylethylbenzylammonium halide, cetylpyridinium halide, and mixtures thereof. Carbonate-hydroxyapatite is, Formula I: Ca (10-x) M x (PO 4 ) (6-2 / 3y) (CO 3 ) y (OH) 2 I It is expressed by, in the formula: M is a metal cation selected from the group consisting of cations of Cu, Mg, Al, Zn, Co, Fe, Ag, Mn, Sr, and Ti, or a combination of such cations; x falls between 0 and 2.5; y is the functionalized carbonate-hydroxyapatite, which is contained between 0.1 and 3.

2. The functionalized carbonate-hydroxyapatite according to claim 1, which is functionalized with the fungicide in an amount ranging from 0.05 wt% to 5 wt% based on the total weight of the functionalized C-Hap.

3. The functionalized carbonate-hydroxyapatite according to claim 1, wherein the bactericide is cetylpyridinium halogenate.

4. The functionalized carbonate-hydroxyapatite according to claim 1, wherein x in formula I is zero.

5. The carbonate-hydroxyapatite according to claim 1, wherein x in formula I is between 0.1 and 2.

6. The carbonate-hydroxyapatite according to claim 1, wherein the metal cation M is selected from the group consisting of Cu, Zn, Ag cations, and combinations thereof.

7. A cosmetic composition comprising functionalized carbonate-hydroxyapatite (C-Hap), wherein the functionalized carbonate-hydroxyapatite comprises 0.05 wt% to 35 wt%, and contains 0.05 wt% to 20 wt% of carbonate, which is functionalized with 0.01 wt% to 10 wt% of a bactericide based on the total weight of the functionalized C-Hap, Here, the disinfectant is selected from chlorhexidine and its salts, benzalkonium halide, diisobutylphenoxyethoxyethyldimethylbenzylammonium halide, alkyldimethylethylbenzylammonium halide, cetylpyridinium halide, and mixtures thereof. Carbonate-hydroxyapatite is, Formula I: Ca (10-x) M x (PO 4 ) (6-2 / 3y) (CO 3 ) y (OH) 2 I It is expressed by, in the formula: M is a metal cation selected from the group consisting of cations of Cu, Mg, Al, Zn, Co, Fe, Ag, Mn, Sr, and Ti, or a combination of such cations; x falls between 0 and 2.5; The cosmetic composition, where y is between 0.1 and 3.

8. The cosmetic composition according to claim 7, comprising 0.5 wt% to 25 wt% of the functionalized carbonate-hydroxyapatite (C-Hap).

9. The cosmetic composition according to claim 7, wherein the composition is an oral care composition or a skin care composition.

Images