Metallic nanoparticle-based dressing

Abstract

The present invention patent application relates to a dressing (1) pertaining to the technical field of medical-use materials; said dressing (1) comprises a textile material body (2) and a medicinally functional element (3) incorporated into the textile material body (2), consisting of copper and / or gold (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver nanoparticles.

Description

[0001] "Wound Dressing Based on Metallic Nanoparticles" Introduction

[0002] [1] This descriptive report refers to a patent application for a dressing, belonging to the technical sector of medical devices; said dressing being based on metallic nanoparticles of copper and / or gold (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver, aiming to stimulate antimicrobial, anti-inflammatory and healing activity.

[0003] STATE OF THE ART - BASIS OF THE INVENTION

[0004] [2] Worldwide, acute and chronic wound infections represent a public health challenge, resulting in significantly high morbidity and mortality estimates. Therefore, scientists have been investigating improved strategies for wound treatment, while conventional practices are routinely used. The major barriers to overcome in the study of new approaches to wound treatment are associated with delayed healing time and resistance to various medications (DING et al., 2022; RYBKA et al., 2023).

[0005] [3] In this context, the development of nanotechnology-based systems has aroused great interest, mainly for biomedical and pharmaceutical applications related to wound healing (KALASHNIKOVA et al., 2015; RAJENDRAN et al., 2018; STOICA et al., 2020). Additionally, nanoparticles have emerged as a promising strategy to minimize microbial resistance, due to their ability to enhance antimicrobial properties (ATAIDE et al., 2017). For example, a study conducted with gold and silver nanoparticles in wound healing demonstrated results of a considerable reduction in the healing period, which can be attributed to their antimicrobial and anti-inflammatory properties (NARAGINTI et al., 2016).

[0006] [4] The use of nanotechnology is scientifically based on the valuable advantage that nanoparticles provide, related to the enhancement of their functionalities (BUZEA et al., 2007; JOUDEH & LINKE, 2022), a quality that is directly associated with surface effects and quantum effects (JOUDEH & LINKE, 2022). This is because nanomaterials have a significantly large surface area, a high number of particles per unit mass, a greater fraction of atoms on the surface, and also because the atoms on the surface of nanomaterials interact with fewer direct “neighbors” (BUZEA et al., 2007; JOUDEH & LINKE, 2022). Additionally, it is also necessary to consider that the amplitude of the effects of nanomaterials is directly related to their size, since the smaller the size of the nanomaterial, the more potent the quantum effects become (JOUDEH & LINKE, 2022).In this way, nanoparticles promote an extremely satisfactory result, since their physical, chemical and biological properties are enhanced in relation to counterparts of the same materials in larger dimensions (BUZEA et al., 2007; JOUDEH & LINKE, 2022).

[0007] [5] It is interesting to add that nanoparticles conjugated with different metals, peptides or selected herbs can exert synergistic effects as antioxidants and anti-inflammatories. All these agents are considered potential candidates for the treatment of chronic wounds (RYBKA et al., 2023). Regarding the antimicrobial properties of silver, the activation mechanism is simultaneously related to several processes, including the formation of complexes with DNA and RNA, enzyme inactivation, protein denaturation through the generation of reactive oxygen species, impairment of ion exchange and membrane disruption (MEDICI et al., 2019). Additionally, silver nanoparticles exhibit an intensified antimicrobial effect since they allow the continuous release of silver cations.Due to this property, silver nanoparticles naturally interact with microbial membranes, leading to cell wall disruption (DAKAL et al., 2016; WAKSHLAK et al., 2015). In addition to their ability to promote the death of microorganisms, silver and silver nanoparticles also stimulate skin regeneration (RYBKA et al., 2023). In this context, it is possible to state that the properties of silver nanoparticles can improve processes related to both infection prevention and wound healing, compared to conventional treatments. Furthermore, there is scientific evidence related to the minimization of bacterial resistance using silver nanoparticles, since the mechanisms induced by this agent are different from those stimulated by standard antibiotics (RYBKA et al., 2023).

[0008] [6] Regarding the antimicrobial effect of zinc oxide nanoparticles, possible related mechanisms have been described, including electrostatic forces, zinc ion release, and the generation of reactive oxygen species, consequently stimulating lipid peroxidation of membranes and damage to DNA and proteins. Beneficial effects that may help combat antibacterial resistance (MENDES et al., 2022; RAYYIF et al., 2021). Similarly to silver nanoparticles, zinc oxide nanoparticles also allow for an intelligent and sustained release of zinc ions, being considered an efficient innovative strategy for wound therapy (RAYYIF et al., 2021).

[0009] [7] Studies using copper nanoparticles have also shown promising results for wound treatment, stimulating direct healing and preventing bacterial infection (DIAO et al., 2023). Importantly, copper is able to accelerate the wound healing process, as it modulates several cytokines and growth factors at all stages of this process (SALVO & SANDOVAL, 2022). Thus, copper nanoparticles assist in the anti-inflammatory process of wounds and promote a significant antimicrobial effect (DIAO et al., 2023; SALVO & SANDOVAL, 2022; SANDOVAL et al., 2022). In addition, copper has been shown to be a metal with favorable biocompatibility for use in dermal dressings (SANDOVAL et al., 2022).

[0010] [8] Thus, based on all these scientific findings, it is possible to state that metallic nanoparticles based on silver, zinc and copper represent a valuable innovation strategy for biomedical applications. Tables 1 to 3 below show publications on the use of metallic nanoparticles in wound dressings.

[0011] Table 1. FDA-approved silver dressings.

[0012] Table 2. Zinc-based dressings approved by the FDA. Dermagran (zinc-saline) wet dressing K913344 - Year 1992 FDA, 2024h

[0013] Table 3. Copper-based dressings approved by the FDA.

[0014] [9] Additionally, corroborating the growing interest in the functionality of using metals in dressings, some patents for dressings containing silver, gold and copper nanoparticles were found (Table 4). No Brazilian patents involving dressings based on metallic nanoparticles were found (INRI, 2024).

[0015] Table 4. Patents found for dressings based on metallic nanoparticles.

[0016]

[0010] The information above shows that acute and chronic wound infections represent a public health challenge, resulting in significantly high morbidity and mortality estimates; it also shows the effective effects of metallic nanoparticles in various health applications, including the use of silver, copper and other nanoparticles in obtaining dressings.

[0011] Despite the good results obtained with the use of metallic nanoparticles in the health field, inventors have continued studies aimed at obtaining improved effects, particularly in wound treatment.

[0017] OBJECTIVES OF THE INVENTION

[0018]

[0012] Thus, based on the knowledge disclosed about nanoparticles in the medical field, the objective of the present invention is the creation of a dressing with metallic nanoparticles.

[0019]

[0013] Another objective is to provide wound care with metallic nanoparticles of copper and / or gold (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver.

[0020]

[0014] Another objective is to provide a dressing with metallic nanoparticles of copper and / or gold (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver, which stimulate antimicrobial, anti-inflammatory and healing activity.

[0021]

[0015] Another objective is to provide means for obtaining the dressing. BRIEF DESCRIPTION OF THE INVENTION

[0022]

[0016] In view, therefore, of the aspects and objectives above and in order to observe and meet them, the dressing based on metallic nanoparticles, object of the present patent application, was developed, which is essentially formed by: a body of textile material, constituting the dressing; and metallic nanoparticles of copper and / or gold (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver incorporated into the textile body.

[0023]

[0017] Although several scientific articles have been published in recent years in academia confirming the antimicrobial potential of metallic nanoparticles, the subject of this patent application, a dressing with copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver, is novel and capable of contributing to the reduction of infections, anti-inflammatory action and corroborating faster healing of patients, as per the main objective of the invention.

[0024]

[0018] Nanoparticle characterization techniques, such as: ultraviolet-visible (UV-Vis), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), provide information regarding the size, shape and composition of copper and / or gold NPs (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver, which have been of paramount importance as they are directly related to the results obtained in the application of these NPs in various areas such as: catalysis, optics, medical, pharmaceutical, electrochemistry and biological activity.

[0025]

[0019] Based on this, the antimicrobial activity of the dressings was investigated against Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria using the disk method. S. aureus bacteria are Gram-positive, with many belonging to the normal microbiota of the upper respiratory tract or skin. E. coli bacteria refer to various genera of Gram-negative bacillus bacteria, being a generalized intestinal parasite of mammals. The ability of dressings containing copper and / or gold NPs (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver supported NPs to inhibit the growth of these bacteria was proven in partnership with specialized institutions (Microbiology and Nanotechnology Laboratories of PUCRS).Tests of the technology were carried out by the applicant, which demonstrated the antibacterial action of metallic NPs, particularly copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver nanoparticles, which occur through their coordination to the surface layer of bacteria, causing the rupture of the peptidoglycan layer and consequent inactivation of the microorganism. The peptidoglycan layer of the gram-negative bacterium (E. coli) is thinner than that of gram-positive bacteria (S. aureus), this fact is probably related to the Au NPs coordinating more easily and efficiently, causing greater inhibition in E. coli bacteria than in S. aureus bacteria.It can be concluded that textile synthesis containing copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver nanoparticles generated an efficient material with a strong antimicrobial effect, proven in tests performed, giving rise to the present patent application.

[0026] LIST OF DRAWINGS

[0027]

[0020] The attached drawings refer to the metallic nanoparticle-based dressing, the subject of this patent application, in which:

[0028] - Fig. 1 shows a schematic view of one possible way to perform the dressing, with the aim of stimulating antimicrobial, anti-inflammatory and healing activity; and

[0029] - Fig. 2 shows a schematic representation of the application of a dressing based on metallic nanoparticles.

[0030] DETAILED DESCRIPTION BASED ON DRAWING

[0021] As illustrated in the figures above and provided for in the invention, the dressing 1, the subject of this patent application, comprises: a body of textile material 2; and an element with a medicinal function 3 incorporated into the body of textile material 2.

[0031]

[0022] In the present invention, and this constituting the main object to be protected in the patent, the element with medicinal function 3 is constituted by copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver obtained by green synthesis and selected to stimulate antimicrobial, anti-inflammatory and healing activity.

[0032]

[0023] In detail, dressing 1 can have any of the normally found constructions, such as, for example, comprising (fig. 1): a body of textile material 2 or other material that absorbs and retains the element with medicinal function 3, this consisting of copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver; a self-adhesive tape 4, with a central region that has adhered to the body of textile material 2 and with adhesive ends free from fixation to the user's body; and a removable protective and release film (liner) 5 or other usual constructions.

[0033]

[0024] The copper and / or gold-based nanomaterial (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver-based nanomaterial used in the present invention is on the order of 9 nanometers. The nanoparticle production process is carried out using green synthesis. An estimated concentration of 0.05 mg / ml of colloidal gold extracted through green synthesis by Curumins, in partnership with the specialized company Peptnano, is obtained. In terms of production, it should be noted that the impregnation of the nanoparticles into bandage fabrics (dressings) is done using a ramo process, and the entire nanoparticle reuse cycle is carried out, resulting in 0% waste.

[0034]

[0025] Figure 2 shows the use of dressing 1, and initially shows: the area of ​​the patient's body (leg) with the wound; an enlarged and cross-sectional detail of the skin, the established infection and the indication for applying dressing 1; the treatment, i.e., dressing 1 applied over the wound and producing the treatment; and the area of ​​skin already healed after treatment.

[0035]

[0026] Studies show that copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver nanoparticles have clear biocompatibility, good stability, and a large surface functionalization area. These characteristics are scientifically supported, as it has been demonstrated in the literature that copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver nanoparticles with a size smaller than 10 nm, synthesized by green synthesis, exhibit high purity, stability, and monodispersity. Importantly, there are studies demonstrating that copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver nanoparticles exhibit potential biological functionalities, including antimicrobial, anti-inflammatory, and wound-healing activities.It should also be noted that the maximum dose of 10 mg / kg has been proven safe for biomedical applications, based on a high-quality scientific study published in Nature (ALJOHANI et al., 2022).

[0036]

[0027] It is therefore emphasized that the copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver nanoparticles, according to the present invention, are obtained through green synthesis, which is an important differentiating factor, since it attests to the absence of toxicity from possible contaminating residues. Additionally, according to the literature, gold nanoparticles (AuNPs) produced by green synthesis exhibit a high level of purity, good stability and monodispersity.

[0037]

[0028] The present dressing appears to be an innovative ingredient, since dressings based on copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver are not currently available on the market. Thus, literature studies were used for the scientifically rational construction of this dressing, since there is clear evidence that gold nanoparticles are capable of acting as potential healing, anti-inflammatory and antimicrobial agents. It is also important to clarify that the development process of this dressing involved concerns not only in the context of efficacy, but also safety for use in humans.

[0038]

[0029] Within the basic construction described above, the nanoparticle-based dressing, the subject of this patent application, may undergo modifications relating to materials, dimensions, construction details and / or functional configuration and / or process steps and / or parameters, without departing from the scope of the protection sought. REFERENCE

[0039] ALJOHANI, FS; HAMED, MT; BAKR, BA; SHAHIN, YH; A- BU-SERIE, MM; AWAAD, AK; EL-KADY, H.; ELWAKIL, BH 2022. In vivo bio-distribution and acute toxicity evaluation of greenly synthesized ultra-small gold nanoparticles with different biological activities. Scientific Reports. 12, 6269. https: / / doi.Org / 10.1038 / S41598-022-10251 -7.

Claims

Claims 1) - “DRESSING BASED ON METALLIC NANOPARTICLES”, comprising: a textile body (2); and an element with a medicinal function (3) incorporated into the textile body (2), characterized in that the element with a medicinal function (3) is constituted by copper and / or gold nanoparticles (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver, obtained by green synthesis and selected to stimulate antimicrobial, anti-inflammatory and healing activity. 2) “WOUND BASED ON METALLIC NANOPARTICLES”, according to claim 1, characterized in that the size of the copper and / or gold nanoparticle (AuNPs) and / or zinc and / or zinc oxide and / or titanium dioxide and / or silver nanoparticle is on the order of 9 nanometers.

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