Antimicrobial fluid based on alginate incorporated with zif-8 type nanoparticles and copper as intracanal medication

Description

[001] The present invention is situated within the field of dentistry, focusing on the specialty of endodontics. More precisely, it refers to the development of intracanal medications intended to treat endodontic infections. Endodontics is an area of ​​dentistry that focuses its efforts on the study and treatment of the dental pulp, aiming at the health and preservation of teeth. In the context of intracanal medications, endodontic treatments often require the application of specific substances within the root canals to eliminate pathogenic microorganisms, control infections, and promote the health of the periapical tissue between treatment sessions. Fundamentals of the invention

[002] In the current state of the art, intracanal medications have been widely used in endodontics to combat infections and promote the recovery of periapical tissues. These medications often consist of liquid or paste formulations that are introduced into the root canals to treat bacterial pathogens and reduce inflammation. Such formulations are frequently based on antimicrobial substances, such as chemical substances or natural compounds, with the aim of achieving satisfactory therapeutic results. However, the state of the art presents significant challenges. Traditional intracanal medications may have limitations regarding antimicrobial efficacy, penetration into the root canals, and control of the release of therapeutic substances. In addition, bacterial resistance to some conventional formulations has been observed, impairing the effectiveness of endodontic treatments.The need for innovative approaches that overcome these limitations is evident. Petition 870250009081, dated 04 / 02 / 2025, page 10 / 22 / 6

[003] The crucial difference between the present invention and conventional approaches lies in the innovative incorporation of copper-loaded Zeolitic Imidazolate Framework-8 (ZIF-8) nanoparticles into an alginate fluid. ZIFs are porous structures composed of metals connected by organic ligands, allowing the creation of a matrix that can gradually carry and release therapeutic substances, such as copper. The introduction of ZIF-8 as a carrier proves advantageous because they possess high adsorption capacity, chemical stability, and can be modulated for controlled release. By incorporating copper nanoparticles into ZIF-8 in a 2% alginate fluid, the invention enables effective antimicrobial action when used in endodontics, targeting Gram-positive and Gram-negative bacteria, including those resistant to conventional treatments.

[004] This synergistic approach to antimicrobial action through programmed, or slow, release reflects very promising potential, especially when considering its application as an intracanal medication or delayed dressing. Furthermore, the ability to control the release of copper nanoparticles through ZIFs amplifies the therapeutic potential and minimizes possible side effects. The use of 2% alginate fluid as a vehicle provides the necessary paste consistency for intracanal application, facilitating introduction and allowing for uniform distribution of the medication. This combination of factors results in a highly effective intracanal medication, capable of overcoming the limitations of the prior art, offering an advanced therapeutic solution for endodontic infections.The innovative approach provides a more complete treatment, with a greater potential for success and a lower risk of bacterial resistance, benefiting both patients and dental professionals. Petition 870250009081, dated 04 / 02 / 2025, page 11 / 22 / 6 Brief description of the drawings Figure 1 shows an image of Cu@ZIF-8, obtained through Scanning Electron Microscopy, measuring the material at 200nm, with particles smaller than 50nm. Figure 2 shows the Fourier Transform Infrared Spectroscopy (FTIR) graph, highlighting the adhesion of copper nanoparticles to the structure. Figure 3 shows the X-ray Diffraction (XRD), demonstrating that the crystallinity of the structure did not change after the incorporation of copper, indicating a high level of purity in the sample. Figure 4 shows the antimicrobial effect of ZIF-8 with and without copper nanoparticles. 6 and 7 (E. faecalis x Cu+ZIF8), 8 and 9 (E. faecalis +ZIF8) Description of the invention

[005] The present invention relates to an innovative intracanal medication for the treatment of endodontic infections, which incorporates copper-loaded ZIF-8 type nanoparticles in a 2% alginate paste fluid. The resulting composition demonstrates enhanced antimicrobial properties and a controlled copper release capability, providing an effective therapeutic approach for resistant endodontic infections.

[006] The invention seeks to address the growing challenge of bacterial resistance in endodontic infections, which has been associated with the persistence of resistant bacteria, contributing to the worsening of periapical lesions. The innovative incorporation of copper nanoparticles into ZIF-8, combined with the alginate fluid formulation, results in an intracanal medication capable of addressing these problems efficiently and in a controlled manner. Petition 870250009081, dated 04 / 02 / 2025, p. 12 / 22 / 6

[007] The intracanal medication developed is the result of the synergy between the antimicrobial action of copper and the properties of ZIF-8 as a controlled-release carrier. Copper nanoparticles act against gram-positive and gram-negative bacteria, including those resistant to conventional treatments. Several studies have reported that different configurations of copper have shown a significant antimicrobial effect against Enterococcus faecalis, which is the microorganism of primary importance in endodontics due to its high capacity to acquire resistance. The ability of ZIF-8 to gradually release copper expands the therapeutic potential and reduces the risk of side effects, providing a more effective and safe treatment for endodontic infections.

[008] The synthesis of copper-loaded ZIF-8 involved the addition of a methanolic solution of 2-methylimidazole and a methanolic solution of zinc nitrate hexahydrate, followed by magnetic stirring and standing. The resulting colloidal suspension was centrifuged, washed with methanol, dried, and stored to obtain ZIF-8. To obtain Cu@ZIF-8, ZIF-8 was added to an ethanol solution containing Cu(NO3)2·3H2O, subjected to magnetic stirring, left to stand, collected by centrifugation, washed with methanol, and subsequently dried under vacuum. Successful confirmation of the synthesis was performed by X-ray diffraction.

[009] Traditional intracanal medications often have limitations in their antimicrobial power, especially against bacteria such as Enterococcus faecalis. The incorporation of copper

[0010] The developed intracanal medication offers an advanced therapeutic solution for endodontic infections, overcoming the limitations of conventional methods. The combination of effective antimicrobial action with the controlled release of copper through ZIF-8 makes the treatment more complete and efficient, reducing the risk of bacterial resistance. This innovative approach benefits both patients, by providing more effective treatment, and dental professionals. Petition 870250009081, dated 04 / 02 / 2025, page 13 / 22 / 6 dental area, by offering a more advanced and promising therapeutic tool for the treatment of endodontic infections. Examples of embodiments of the invention

[0011] To illustrate the various possibilities for implementing the present invention, examples of formulations of 2% alginate fluid loaded with ZIF-8 type nanoparticles incorporated with copper (Cu@ZIF-8) and their respective copper concentrations will be presented. It is worth noting that the concentrations and proportions mentioned in the examples are only illustrative and do not limit the invention to these specific configurations. Example 1: 2% alginate fluid containing Cu@ZIF-8 nanoparticles with a copper concentration of 0.1% (w / w). Example 2: 2% alginate fluid containing Cu@ZIF-8 nanoparticles with a copper concentration of 0.5% (w / w). Example 3: 2% alginate fluid containing Cu@ZIF-8 nanoparticles with a copper concentration of 1.0% (w / w).

[0012] The efficacy of the developed intracanal medication was evaluated through comparative tests with other therapeutic approaches. In previous studies conducted by SIQUEIRA et al. (2014), the antimicrobial activity of red propolis extract was evaluated against Enterococcus faecalis, resulting in a Minimum Inhibitory Concentration (MIC) of 18 mg / ml for the red propolis extract at a concentration of 7.5%. This means that to inhibit Enterococcus faecalis, a quantity of 18 mg / ml of the red propolis extract solution was necessary. In contrast, tests using the Cu@ZIF-8 compound revealed an MIC of 3 mg / ml, demonstrating a superior inhibitory capacity. That is, only 3 mg / ml of Cu@ZIF-8 was sufficient to completely inhibit the growth of Enterococcus faecalis. These results indicate that the copper nanoparticles incorporated into the ZIF matrix possess a Petition 870250009081, dated 04 / 02 / 2025, page 14 / 22 / 6 more robust potential in inhibiting the growth of E. faecalis when compared to red propolis.

[0013] In comparison with the study by Caroline Zamin (2017), which evaluated the essential oil of Tetradenia riparia (Triparia) against Enterococcus faecalis, interesting reflections arise. While Triparia presented a MIC of 0.3 mg / ml as an immediate irrigating agent, our Cu@ZIF-8 demonstrated a MIC of 3 mg / ml as a controlled-release intracanal medication. The differentiated application of these agents raises questions about the influence of time. While the essential oil exhibits an immediate effect, Cu@ZIF-8, as a delayed dressing, potentiates the constant antimicrobial presence throughout the treatment. When comparing MICs, considering the nature of the applications and their effects on endodontic treatment is fundamental. Cu@ZIF-8, as a delayed dressing, offers a prolonged effect, highlighting its potential for effective and continuous antimicrobial therapy in the root canal environment.

[0014] It is important to emphasize that all the essential information for understanding and reproducing the present invention is described in this section. The variations presented in the examples serve as illustrations of possible embodiments of intracanal medication, focusing on enhanced antimicrobial efficacy, offering more effective and specific solutions for the treatment of intracanal bacterial infections.

Claims

1. Intracanal medication characterized by comprising an alginate fluid incorporated with ZIF-8 type nanoparticles and copper, where the polymer is added to a viscous alginate fluid, resulting in a paste-like consistency to facilitate application in root canals.

2. Intracanal medication according to claim 1, wherein ZIF-8 type nanoparticles are characterized by providing a controlled release of antimicrobial agents, serving as a carrier and generating an effective therapeutic effect against resistant microorganisms.

3. Intracanal medication according to claim 1, characterized by the incorporation of copper into the ZIF-8 matrix, enhancing the antimicrobial capacity of the material, increasing its effectiveness in combating endodontic infections.

4. The intracanal medication, according to the preceding claims, is characterized by having a 2% viscous alginate fluid in its formulation, giving the medication a pasty consistency that facilitates its precise and uniform application in the root canal system, allowing for a longer action time.

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