ANTIMICROBIAL ADHESIVE COMPOSITION WITH COPPER NANOPARTICLES FOR DENTURES

Abstract

The present invention concerns a new antimicrobial denture adhesive composition useful to be used for fixing dentures, which includes copper nanoparticles (CuNPs) that provides antimicrobial properties against dental pathogens such as Candida albicans, Streptococcus mutans, Staphylococcus aureus and Aggregatibacter actinomycetemcomitans. Surprisingly, the composition for a denture adhesive comprising copper nanoparticles (CuNPs) not only shown excellent antimicrobial properties, but also improved adhesive properties in comparison with other denture adhesives existing currently in the marked, which do not contain said CuNPs.

Claims

1. Antimicrobial denture adhesive composition, comprising: a cellulose polymer or its derivative; a copolymer of methyl vinyl ether and maleic anhydride (PVM/MA) or their derivatives; copper nanoparticles (CuNPs); and a hydrophobic vehicle.

2. Antimicrobial denture adhesive composition according to claim 1, comprising: mineral oil between 20.0 to 30.0 w/w %; petrolatum between 25.0 to 35.0 w/w %: copolymer of methyl vinyl ether and maleic anhydride (PVM/MA) between 28.0 to 37.0 w/w %; carboxymethylcellulose between 14.0 to 23.0 ; and copper nanoparticles (CuNPs) between 0.030-0.100 w/w %.

3. Antimicrobial denture adhesive composition according to claim 1, wherein copper nanoparticles (CuNPs) have dimensions of 5 to 200 nm.

4. Antimicrobial denture adhesive composition according to claim 1, wherein copper nanoparticles (CuNPs) have a morphology selected from the group consisting in spherical, tubular, cubic, fibrous, wire, laminar and any other morphology having at least one of its dimensions in nanometric scale.

5. Antimicrobial denture adhesive composition according to claim 1, wherein said copper nanoparticles (CuNPs) contain copper having an oxidation number of 0, 1, 2 or one intermediate oxidation state.

6. Antimicrobial denture adhesive composition according to claim 1, wherein said copper nanoparticles (CuNPs) has a structure of copper supported on ceramic nanoparticles selected from the group consisting in silica, clay, zeolite, titanium and zirconium oxides.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0031] FIG. 1 Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy spectrum of the Corega® denture adhesive compared to a preferred formulation of the denture adhesive composition containing copper nanoparticles (CuNPs) of the invention.

[0032] FIG. 2 Compositional analysis of the preferred formulation of the denture adhesive composition containing copper nanoparticles (CuNPs) performed by Energy Dispersive X-Ray Analysis (EDX) coupled to Scanning Electron Microscopy (SEM).

[0033] FIG. 3. Shows antibiograms of the Corega® prosthesis adhesive compared to a preferred formulation of the prosthesis adhesive composition containing copper nanoparticles (CuNPs) of the invention against the Candida albicans fungus.

[0034] FIG. 4. Shows the adhesive strengths of two commercial prosthesis adhesives compared to the prosthesis adhesive composition containing copper nanoparticles (CuNPs) of the invention measured by mechanical tensile tests.

DETAILED DESCRIPTION OF THE INVENTION

[0035] The present invention focuses on the development of a new composition for a denture adhesive with antimicrobial properties to be used in fixing dentures in people in need of it.

[0036] Surprisingly, the composition for a denture adhesive comprising copper nanoparticles (CuNPs) not only shown excellent antimicrobial properties, but also improved adhesive properties in comparison with another denture adhesives existing currently in the marked, which do not contain said CuNPs.

[0037] The denture adhesive composition of the invention comprises also an hydrophobic carrier or vehicle selected from petrolatum or petrolatum combined with mineral oil, natural wax, synthetic wax, polyvinyl acetate, natural oils, synthetic oils, fats, silicone, silicone derivatives, dimethicone, silicone resins, hydrocarbons, hydrocarbon derivatives, essential oils, caprilic/capric triglycerides, polybutene, oleic acid, stearic acid, and combinations thereof; and a polymer material derivated from cellulose selected from hydroxypropyl methylcellulose, carboxymethyl-cellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxyethylmethylcellulose, hydroxyethylmethylcellulose, methyl-cellulose, methylcarboxymethyl cellulose, hydroxyethylcarboxymethyl cellulose, hydroxyethylmethylcarboxy methylcellulose, sulfoethylcarboxymethyl cellulose, hydroxyethylhydroxypropyl cellulose, hydroxyethylethyl cellulose, hydroxyethylsulfoethyl cellulose or combinations thereof.

[0038] In a preferred embodiment, the polymer material derivate from cellulose is carboxymethyl-cellulose.

[0039] The invention further comprises a polymer material selected from poly(methylvinyl ether-co-maleic acid) (PVM/MA) and its derivatives, such as acids, salts or anhydride.

[0040] In addition to the above-mentioned components, the present composition may optionally contain other components to improve or enhance the adhesive nature of the base components, including those commonly known and used by the denture adhesive industry. Examples include but are not limited to dicalcium phosphate and nanoclay.

[0041] The dental adhesive composition of the invention may comprise additional components, such as plasticizers, rheology modifiers, preservatives, humectants, emulsifiers, antioxidants, super-disintegrants or absorbents, flavoring agents, colorants, cross-linking agents, non-metallic antimicrobial agents, control release agents, antifoaming agents, sweetening agents and viscosity modifiers.

EXAMPLES

1. Example 1

Obtaining CuNPs

[0042] Copper nanoparticles (CuNPs) can be obtained using well known technologies (Madhulika Bhagat et. al., Review—Multifunctional Copper Nanoparticles: Synthesis and Applications, ECS Journal of Solid State Science and Technology, 2021, 10, 063011).

[0043] Alternatively, enveloped CuNPS in ceramic material particles can be prepared. For that, zeolite particles (nanoporous crystalline aluminosilicate) and silica nanoparticles were used as support materials, using natural zeolite of national origin (MOR) and commercial 100 nm silica nanoparticles. CuNPs are formed on site in the material, whereby a certain MOR mass was contacted with a 0.1 M copper acetate solution for 24 h at room temperature. Once the ion exchange period was completed, the zeolite was separated and washed by repeated centrifugation/dispersion cycles. The resulting material was then dispersed in a starch/ascorbic acid reducing solution and microwaved for a few seconds.

[0044] This system for the formation of CuNPs in biopolymers was developed by our laboratory team under the concept of “Green Chemistry”, with the aim of synthesizing more benign metallic nanoparticles that are compatible with biomedical applications. The CuNPs/MOR particles were separated, washed and dried for further use in the preparation of the antimicrobial denture adhesive composition.

2. Example 2

Preparation of the Antimicrobial Denture Adhesive Composition Containing CuNPs

[0045] 25 g of mineral oil (w/w) and 28.4 g of petrolatum (w/w) are mixed at 60° C. under a stirring speed of 300 ppm for 10 minutes. Next, 0.071 g of copper nanoparticles (w/w) are added and the mixture is stirred at the same temperature for 10 minutes. Next, 31.6 g of PVM/MA (w/w) and 14.9 g of carboxymethylcellulose are added (w/w), and the resulting mixture is stirred for 40 minutes at 60° C. The product obtained is allowed to cool to room temperature.

[0046] In order to compare the chemical structure of the antimicrobial denture composition with CuNPs with known denture adhesives in the market, adhesives were analyzed by using total attenuated reflectance with Fourier transform infrared spectroscopy (ATR-FTIR) in an Agilent Cary 630 ATR-FTIR spectrometer.

[0047] FIG. 1 shows the results of said ATR-FTIR analysis, which evidences that the denture adhesive modified with CuNPs have the same spectrum than that of Corega®, so the presence of CuNPs does not alter the structure of the denture adhesive.

[0048] Additionally, the adhesive elemental composition was analyzed by X-ray dispersive energy spectroscopy (EDX) coupled to scanning electron microscopy (SEM) in a JEOL model JSMIT300LV microscope. FIG. 2 shows Copper EDX elemental mapping of the denture adhesive formulated with CuNPs, which confirms the incorporation of CuNPs in the PVM/MA adhesive matrix.

3. Example 3

In-Vitro Assessment of the Antimicrobial Properties of the Antimicrobial denture adhesive composition containing CuNPs

[0049] Antimicrobial properties of the denture adhesives were assessed against Candida albicans, pathogen responsible of denture stomatitis disease, by using the agar disk-diffusion method. Filter paper discs of 6 mm in diameter were impregned with the denture adhesives for 20 minutes. After that, 100 μL of 0.5 Mcfarland (1-5×106 CFU/ml) of ATCC 90029 strain of Candida albicans were seeded on plates of Sabouraud dextrose agar medium. Then, adhesive—impregnated disks were placed onto the surface of the inoculated agar plate. Each disk was pressed down to ensure complete contact with the agar surface, and they were distributed evenly so that they were no closer than 24 mm from center to center. The plates were incubated at 37° C. under aerobic conditions for 48 hours after which the disks were applied. Plates were examined after 48 h of incubation (FIG. 3). The diameters of the resulting zones of inhibition were measured to the nearest whole millimeter at the point at which there was a prominent reduction in growth.

4. Example 4

Determination of the Improved Adhesive Properties of the Antimicrobial Denture Adhesive Composition Containing CuNPs

[0050] Adhesive properties were measured by using mechanical tensile tests in a DEBEN microtest machine (Suffolk, UK) using a 2 N load cell. Denture adhesives were applied on the surface of two dental acrylic specimens having a flat area of 60 mm.sup.2 and perpendicular to the long axis. The two acrylics were bonded and immersed in artificial saliva for 5 minutes to ensure adhesion between opposing acrylic specimens. After that, the specimens were debonded in tensile mode at a rate of 1 mm per minute by using the microtest machine. The maximum force before failure was then calculated (adhesive resistance).

[0051] The presence of CuNPs in the adhesive also gives it improved adhesive properties (FIG. 4).

[0052] The tensile mechanical properties of the adhesive formulated with CuNPs are shown compared to other commercially available prosthetic adhesives. The adhesive strength of denture adhesive with CuNPs was statistically higher than that of two of the more well-known commercial adhesives currently in the market. These results demonstrate that CuNPs also produce a mechanical reinforcement of the adhesive which provokes greater fixation and stability of dental prostheses in users.

Advantages of the Present Invention

[0053] The antimicrobial denture adhesive composition containing CuNPs has been validated in its antimicrobial and adhesive properties. It has been obtained an optimized formulation that maximizes its antimicrobial and mechanical properties.

[0054] The scaling steps of the said adhesive composition making process were completed in a cosmetic/pharmaceutical/dental industrial plant. Likewise, a pilot of the packaging process of the new adhesive was carried out.

[0055] A product satisfaction and validation study is currently being carried out in a population of 30 patients compared to the conventional Corega® adhesive.