Liquid dressing composition, liquid dressing, process for producing a liquid dressing, and associated use

Abstract

The present invention discloses a liquid dressing composition, a polyvinylpyrrolidone-based liquid dressing containing extracts of pomegranate peel and rosemary, and the use of said liquid dressing. Furthermore, the present invention relates to a process for manufacturing the liquid dressing. The claimed invention makes use of agro-industrial residues, thereby providing a positive environmental impact, in addition to employing biocompatible and low-cost ingredients. The present invention falls within the field of the pharmaceutical industry.

Description

[0001] Liquid dressing composition, liquid dressing, liquid dressing production process and associated uses.

[0002] Field of invention

[0003]

[0001] The present invention is situated in the pharmaceutical field as a liquid dressing for skin wounds, to prevent the growth of microorganisms common to skin infections. The liquid dressing, disclosed herein, protects the wound site by means of a thin polymeric film after the product has dried.

[0004] Fundamentals of the invention

[0005]

[0002] Liquid dressings are products applied in liquid or paste form to the wound and which, when dried by evaporation of the solvent, form a polymer film that protects the area. These systems can be obtained from the combined application of film-forming agents, "softening" or "wetting" agents, specific solvents (ethanol and / or water) and other additives.

[0006]

[0003] Proper wound care is a relevant issue for healthcare systems worldwide. Given the severity of problems associated with inadequate wound management, the development of wound healing technologies has had a growing economic impact. According to a review published in 2023 (Freedman et al. 2023 - doi: 10.1126 / sciadv.ade7007), in the United States alone, in 2014, health problems linked to skin wounds affected more than 8 million people, costing approximately $30 billion. Furthermore, according to the same publication, the characteristics of the increasingly aging and obese population have considerably affected the size of the wound care products market, which reached $21.4 billion in 2022, with a compound annual growth rate of 4.15% from 2023 to 2030.

[0007]

[0004] The growth of this market and the various problems currently encountered with conventional dressings have increased interest in the development of more technological dressings. Among the disadvantages of "conventional" dressings are inadequate antimicrobial properties, inability to provide moisture, weak mechanical characteristics, low biodegradability and biocompatibility, therefore requiring regular changes to prevent them from becoming foci of infection, as well as the combined application of medications with antimicrobial properties for the proper treatment of wounds.

[0008]

[0005] The application of synthetic antimicrobial agents effective against microorganisms common to skin infections, while important, can lead to several complications. It is known that the indiscriminate application of antibiotics increases the spectrum of exposure of microorganisms to them, resulting in increased selection pressure and thus facilitating the development of resistance mechanisms. Such mechanisms are a major challenge and have been driving the development of research evaluating the effectiveness of applying natural antimicrobial agents, such as plant extracts rich in phenolic compounds, in a wide variety of formulations.

[0009]

[0006] The application of extracts has been explored not only as an excellent technological alternative, but also as an environmental solution, since raw materials rich in these compounds can be agro-industrial residues that go from being discarded to being a source of new products. Although "botanical preparations" have been effectively used since the dawn of human civilization, in the last 20 years they have been gaining more attention from researchers and the chemical, cosmetic, pharmaceutical and food industries. As cited by Dias et al., 2021, doi: https: / / doi.org / 10.1016 / j.ultsonch.2021.105584, the global market for natural ingredients is projected to grow annually at a rate of 7.1% from 2019 to 2024, reaching a market value of US$ 43 billion by the end of 2024.

[0010]

[0007] Among the bioactive compounds of greatest interest in the life sciences and chemical sectors are phenolic compounds, known for their antioxidant, antitumor, and antibacterial activities. In fact, several studies found in the literature investigate and point to the antibacterial activities of various phenolic compounds, indicating, therefore, that these substances have a supposed potential for application in the treatment and reduction of skin infections, especially in wounds.

[0011]

[0008] Different phenolic compounds can be obtained from a wide variety of plants, fruits, and agro-industrial waste. As discussed by Ricciardi et al., 2020, doi: https: / / doi.org / 10.1177 / 0734242x20904426, the search for new applications for agro-industrial waste is important for reducing environmental pollution and represents an interesting opportunity to utilize natural waste at low / zero cost, representing a fundamental step in the 'closed loop' of a circular economy. According to the state of the art, "circular economy" has as its main defining element the restorative use of resources, since it considers that raw materials should no longer become useless waste. In this sense, the main concept is not to generate excessive waste, making any waste a new resource.

[0012]

[0009] The use of agro-industrial waste is therefore an interesting alternative, from an environmental and economic point of view; however, for the proper extraction, analysis and application of the compounds, a careful choice of methods and technologies to be applied is necessary, mainly considering the difficulties of scaling up production to industrial levels.

[0013]

[0010] Although some technologies are being developed to minimize the problems and limitations of conventional dressings, many of them involve the application of robust, expensive techniques that are difficult to scale up to industrial levels, reducing the commercial potential of new products.

[0014]

[0011] The state of the art offers some alternatives to conventional dressings. Among them, the most discussed involves the production of films with materials that are more biocompatible than the plastics commonly used for dressing production. Studies involving the production of chitosan films for application as dressings involve the determination of formulations and characterizations of chitosan-based films, which are described as potential solutions to traditional dressings. However, these systems have a relatively high added value, in addition to still involving the same problem of more difficult application (compared to the practicality of liquid dressings based on polyvinylpyrrolidone - PVP) and the potential need for dressing changes, just like conventional dressings.Furthermore, films based on various polymers have been developed with the potential to be applied as dressings; however, the application of these films is very similar to that of a conventional dressing, presenting similar disadvantages.

[0015]

[0012] Furthermore, there is also the development of nanofibers for application as dressings, which, although presenting potential and advantages over conventional dressings, the application of nanofibers as dressings is similar. In addition, the production processes of nanofibers are, in general, more complex and technologically advanced than the technique applied to the production of the liquid dressing discussed in this proposal, besides involving the application of materials with higher added value. Therefore, this solution would be difficult to scale to industrial levels and its commercialization (if possible) would be aimed at a smaller niche of a public with greater purchasing power.

[0016]

[0013] Additionally, the production of solid / film / conventional dressings containing extracts, in these cases, although there is the application of extracts with potential antimicrobial activity (often cited, but not always tested), has the problem of the less practical application of dressings similar to conventional ones compared to liquid dressings, in addition to the need for changes.

[0017]

[0014] Patent document WO23088120 discloses a hemostatic composition containing cannabidiol, comprising, in parts by mass, 0.05 to 2 parts cannabidiol, 2 to 40 parts rhizoma bletillae, 5 to 40 parts pseudo-ginseng extract, 5 to 40 parts rhizoma corydalis extract, 20-80 parts polyvinylpyrrolidone, 1-20 parts poloxamer, 0.01-5 parts an antioxidant, 0.05-10 parts polyethylene glycol and 30-120 parts absolute ethyl alcohol. The hemostatic composition can be used as a liquid dressing for emergency treatment of the surface of a skin wound.

[0018]

[0015] Although patent document W023088120 refers to a liquid dressing composition, the described composition contains a greater number of ingredients with technological functions equal to, or at least similar to, those of the present invention, implying potential cost increases without necessarily positive implications for the product characteristics. In the case of film-forming ingredients, for example, in addition to PVP, the W023088120 formulation also includes Bletilla striata gum, described in the document as a natural film-forming agent. Furthermore, the proposed / necessary concentration of PVP in such a matrix is ​​higher than that applied in the present invention, resulting in a cost increase without added value.

[0019]

[0016] Furthermore, another difference between WO23088120 and the invention now proposed is the time required for the preparation of the formulation, which is more than 36 hours, much longer than the preparation time of the formulation disclosed here. In addition, it is not evident in WO23088120 how the extracts applied in the formulation are prepared and characterized, and depending on the techniques, such applications may affect the cost and feasibility / ease of scaling up production of the dressing taught in WO23088120 with respect to industrial levels.

[0017] Moreover, several studies in the literature discuss the need for a heating step, even a mild one, of PVP dispersions so that the ingredient can be satisfactorily applied as a film-forming agent, and this step is not described in WO23088120.Another difference between patent document WO23088120 and the present invention is the high concentration of ethanol in the WO23088120 formulation, which is for application to wounds, and this can cause significant discomfort to the patient.

[0020]

[0018] Patent CN109731132 refers to a liquid dressing for the relief of arthralgia containing Ginger PE, including the following parts by weight: 2 parts Ginger PE, 1 part Chinese medicinal extract, 1 part peach oil extract, 2 parts elm bark extract, 10 parts chitosan, 30 parts cellulose acetate, 5 parts polyvinylpyrrolidone, and the mass fraction is 100 parts of 95% ethanol solution; wherein, the ethanol solution adjusts the pH to 8~9 using borate buffer solution whose pH is 9.5. The liquid dressing for the relief of arthralgia of the present invention containing Ginger PE not only has the function of effectively relieving arthralgia, but can also form a fast film on the skin surface.

[0021]

[0019] The formulation disclosed in patent CN109731132 presents some technical limitations that greatly differentiate it from the invention now proposed, including the types of ingredients used. Although the formulation is used for the production of a liquid dressing that also contains PVP and an extract, the amount of PVP used in the present invention is smaller (and the extract is ginger, with a different technique and, mainly, different solvents). Regarding the film-forming agent, the present invention uses PVP as an "adjuvant" agent, and PVP is not the main film-forming agent, since the ingredient in higher concentration that presents this capacity is chitosan, which is known to be more expensive.

[0022]

[0020] Another difference between the invention now proposed and patent CN109731132 lies in the solvents used to produce the extracts applied in the formulation, which include: methanol, acetone, N,N-dimethylformamide, dimethyl sulfoxide, tetrahydrofuran, and sulfuric acid. The application of these solvents represents an environmental risk, especially when considering the scaling up of production of this dressing to industrial levels for commercialization. Finally, another relevant difference between the present invention and the Chinese patent is the dressing production process, which involves the application of a high concentration of ethanol, which can cause discomfort during application, and raises the pH to 9, a factor that may represent a problem with regard to industrial scaling.

[0023]

[0021] Patent document EP4217013 discloses a fast-drying liquid dressing containing a film-forming composition for wound protection and prevention of wound contamination, indicated for use on wounds including paper cuts, cuticle cuts, minor wounds, scratches, and abrasions. The liquid dressing may include one or more additives. In one embodiment, the additive is a wound-healing agent and / or an exudate absorbent. Additives may also include antimicrobials, antiseptics, pain reducers, transepidermal water loss (TEWL) prevention materials, and ion-exchange ingredients. Furthermore, the liquid dressing of patent EP4217013 provides wound isolation under a breathable or non-breathable film, which can remain covering the wound without the need for dressing changes, provides waterproofing, and can maintain adherence to the skin for up to a week or more.

[0024]

[0022] However, patent document EP4217013 teaches a general composition of a liquid dressing composition option that includes the application of 1 to 30% of the composition's weight of solvent, which is a very low concentration and possibly difficult to administer to wounds. Furthermore, the European patent document describes the use of alcohol, ketones, ethers, and ethyl acetate as possible solvents to be applied, without revealing the concentrations, and without considering the discomfort of applying these solvents to skin wounds. The film-forming material, according to patent document EP4217013, comprises pyroxylin, in concentrations ranging from 1 to 50%, which is higher than the concentration used in the present invention.

[0025]

[0023] Furthermore, in patent document EP4217013, the application of alcoholic extracts is cited as having the function of "exudate absorbents". In contrast, in the present invention now proposed, the pomegranate peel and rosemary extracts produced with water and ethanol are completely dried before application and are used in the composition only as antimicrobial agents and not as exudate absorbents. In addition, the list of ingredients with antimicrobial function in the European patent document does not include the pomegranate peel and rosemary extracts used in the present invention. Finally, patent document EP4217013 describes the names of several active pharmaceutical components, but provides little detail on their use in the composition and, therefore, does not reveal the effectiveness of the bioactivity of these compounds in the liquid dressing.

[0026]

[0024] Patent document CN110124095 refers to a type of antibacterial liquid adhesive dressings and a method of preparing them. The antibacterial liquid adhesive dressing includes the following components: Doxycycline, NC Nitrocellulose, Bletilla striata extract, plasticizer, liquid solvent, preservative. It is prepared using nitrocellulose film-forming. The addition of doxycycline as an antibacterial substance in prescription materials has expanded its range of clinical and life applications, especially in minor wounds, although infection by microbial pathogens may occur, thus improving the effect.The antibacterial liquid adhesive dressing quickly forms a thin film at the site of skin trauma, offering preferable mechanical performance, adequate damage protection for any body position, and ensuring patient comfort. Due to its hydrophilic nature, it allows moisture to be transported, ensuring wettability of the wound surface and preventing tissue fluid retention, thus benefiting cell growth and migration to promote wound healing.

[0027]

[0025] In contrast to the present invention, patent document CN110124095 uses different ingredients and production processes for the dressings, the main differences being the film-forming agents (use of nitrocellulose, ethyl acetate as a solvent), and, most importantly, the function of the added extracts. While the extract in the Chinese application is an anticoagulant, in the invention now proposed the extract is an antimicrobial agent. Furthermore, the composition of the liquid dressing in the Chinese patent document uses a synthetic antibiotic.

[0028]

[0026] As noted, the state of the art would benefit from a solution that presents a liquid dressing in which the production process of the extracts, the extraction technique, is simpler with the use of green solvents, namely ethanol and water. Furthermore, the present invention makes use of agro-industrial waste with proven antimicrobial properties (positive environmental impact), uses biocompatible and low-cost ingredients. Moreover, the low percentage of ethanol in the formulation reduces the potential discomfort resulting from the application of higher concentrations of this solvent. In addition, the production process of the dressings is simple and uses less expensive technologies. The liquid dressings are easy to apply and maintain, do not require constant changes, and are waterproof.Finally, for this liquid dressing, there is no need to apply medications with antimicrobial properties, as it contains extracts with proven antimicrobial properties.

[0029] Brief description of the invention

[0030]

[0027] The present invention relates to a liquid dressing composition comprising polyvinylpyrrolidone between 10 and 20% (w / v), preferably 20% w / v; glycerol between 1 and 7% (w / v), preferably 7%; carboxymethylcellulose (CMC) between 1.5 and 3% (w / v), preferably 3%; xanthan gum (GX) between 0.1 and 1%, preferably 1%; water between 90 and 100% (v / v), preferably 95%; ethanol between 1 and 10% (v / v), preferably 5%; pomegranate peel extract from 2 to 20 mg / mL; and rosemary extract from 2 to 20 mg / mL.

[0031]

[0028] Furthermore, a second embodiment of the invention reveals a liquid dressing, homogeneous and viscous, that dries quickly after application.

[0032]

[0029] Furthermore, a third embodiment of the invention disclosed herein is the process for producing the liquid dressing, which comprises the following steps:

[0033] (i) Hydrate the PVP mass and the dried pomegranate peel and rosemary extracts with a 5% ethanol solution in ultra-purified water;

[0034] (ii) Heat the composition from step (i) to 60°C for 10 minutes in a water bath;

[0035] (iii) Cool the composition from step (ii) to room temperature for approximately 15 minutes; (iv) Add 7% w / v glycerol, 3% w / v carboxymethylcellulose and 1% w / v xanthan gum to the composition from step (iii).

[0036]

[0030] Finally, a fourth embodiment of the invention now proposed is the use of the liquid dressing.

[0037] Brief description of the figures

[0038]

[0031] Figure 1 illustrates the schematic of the conventional sequential extraction process applied to the initial screening step of extracts for evaluation of antimicrobial activity.

[0032] Figure 2 illustrates the schematic representation of the method for determining the minimum inhibitory concentration.

[0039]

[0033] Figure 3 illustrates the schematic representation of the method for producing inoculum for the development of the minimum inhibitory concentration determination test.

[0040]

[0034] Figure 4 illustrates the chromatogram obtained at 330 nm for rosemary extracts.

[0041]

[0035] Figure 5 illustrates the UV and MS ([MH]-) spectra of the peak with a retention time of 1.389 min from the chromatogram obtained at 330 nm for the rosemary extract.

[0042]

[0036] Figure 6 illustrates the calibration curve obtained from the analysis of known concentrations of pure Rosmarinic Acid.

[0043]

[0037] Figure 7 illustrates the chromatogram obtained at 370 nm for pomegranate peel extracts.

[0044]

[0038] Figures 8A and 8B illustrate the UV and MS ([MH]-) spectra of the peak with a retention time of 2.852 minutes from the chromatogram obtained at 370 nm for pomegranate peel extracts.

[0045]

[0039] Figure 9 illustrates the calibration curve obtained from the analysis of known concentrations of pure ellagic acid.

[0046]

[0040] Figure 10 illustrates the representation of the visual aspect of heterogeneous samples with phase separation in the presence of starch.

[0047]

[0041] Figure 11 illustrates the visual aspect of the samples that formed brittle films that cracked upon drying on the surface.

[0042] Figure 12A, Figure 12B and Figure 12C illustrate the visual aspects of the samples with formulation K2, after preparation (Figure 12A), immediately after application while still wet (Figure 12B), and after drying (Figure 12C).

[0048]

[0043] Figure 13A, Figure 13B, Figure 13C, Figure 13D and Figure 13E illustrate the visual aspects of the liquid dressing samples containing the extracts at different stages of the production and application process: (Figure 13A) extracts of dried pomegranate peel and rosemary; (Figure 13B) K2 formulation with added extracts before the heating stage; (Figure 13C) K2 formulation with added extracts after heating; (Figure 13D) K2 formulation with added extracts before drying; (Figure 13E) K2 formulation with added extracts after drying.

[0049] Detailed description of the invention

[0050]

[0044] The invention discloses liquid bioactive dressings based on polyvinylpyrrolidone (PVP) containing pomegranate peel and rosemary extracts.

[0051] - Development of liquid dressing (a) Screening stage of extracts from various agro-industrial residues with antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Malassezia (common to skin wounds) with the selection of the two best extracts (pomegranate peel and dried rosemary);

[0052] (b) Preliminary testing phase of liquid dressing formulation, with the production of systems with different concentrations of polyvinylpyrrolidone (PVP), glycerol, xanthan gum (GX), carboxymethylcellulose (CMC), and ethanol:water ratios, in addition to tests with starch;

[0053] ( c ) Production of liquid dressings with the best formulation (visual appearance and drying speed - PVP 20% w / v, glycerol 7% w / v, CMC 3% w / v, GX 1% w / v) with different concentrations of extracts (based on the minimum inhibitory concentration and the minimum bactericidal concentration of the extracts).

[0054] Samples

[0055]

[0045] For the initial screening of samples, extracts were prepared from the following agro-industrial residues / samples: orange peel, mango peel, apple peel, grape peel, mango leaf, coffee husk, lemon peel, pomegranate peel, guava leaf, coffee grounds, melon seed, and rosemary. The samples were dried, ground, appropriately sieved to select a particle size range, and stored at -18 °C until used in the experiments. All these samples were used for the production of extracts and evaluation of antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Malassezia. From the initial screening, two samples were selected for the development of the project: pomegranate peel and rosemary.

[0056] Initial screening of extracts from agro-industrial waste

[0057] Production of extracts by conventional extraction methods

[0046] A conventional extraction protocol was used to develop a sweep of extracts from agro-industrial waste: orange peel, mango peel, apple peel, grape peel, mango leaf, coffee peel, lemon peel, pomegranate peel, guava leaf, coffee grounds, melon seed and rosemary. For this, the samples were sanitized, chopped, oven-dried at 60 °C for 24 hours and ground in a food blender. The resulting powder was then passed through sieves to select the appropriate particle size (48 and 32 mesh) and stored at -18 °C.

[0058]

[0047] For the production of the extracts, the dried and ground samples were processed, subjected to three consecutive extractions of the same material, in the following sequence: (1) distilled water, (2) distilled water: ethanol and (3) ethanol (2 g / 25 ml in each step), as schematized in Figure 1. In each step, the solvent was added to the sample, which was then subjected to ultrasound (Elmasonic P - Elma Schmidbauer GmbH, Singen, Germany - 37 Hz, sweep mode at room temperature) for 1 hour, followed by centrifugation (Benchtop centrifuge, model K241R, Centurion Scientific West Ashling, UK) at 10,600 rcf, 25 °C for 10 minutes, and collection of the supernatant. The extracts from each step were mixed and concentrated in a rotary evaporator. The concentrated extract was then dried in a freeze dryer (L101 freeze dryer, Liotop, São Carlos, SP, Brazil). The dried extracts were subsequently processed and tested for their antimicrobial activity.

[0059] Evaluation of the antimicrobial activity of the extracts - Treatment of the extracts to increase solubility

[0048] To evaluate the antimicrobial activity of the extracts, the dry samples were initially treated to increase their solubility in water using polyvinylpyrrolidone. For this, 100 mg of dry extract was added to a solution of polyvinylpyrrolidone (PVP) in ethanol (40 mg / ml), so that the mass of PVP added to the system was 4 times greater than the mass of dry extract. After obtaining homogeneous dispersions (in some cases with the aid of an ultrasonic bath), the samples were dried in a rotary evaporator (Fisatom 802 D, Fisatom, São Paulo, SP, Brazil), and left in a vacuum oven (Vacuum oven, Equatherm) at 50 °C for 12 hours to ensure complete drying. Subsequently, the dried samples were dispersed in water (8 mg / mL) for microbiological analyses.

[0060] Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)

[0061]

[0049] Minimum inhibitory concentration (MIC) analyses were performed in sterile 96-well microplates, in which 100 pL of Mueller-Hinton broth culture media for Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa, and "Malassezia broth" for Malassezia were deposited in each well. Subsequently, 100 pL of concentrated extract (8 mg / mL) were added to the first column in the plate (each row intended for a specific extract), and in subsequent columns, serial dilutions of the extracts were made (i.e., 100 pL of the "broth + extract" sample from column 1 were added to column 2, from column 2 to column 3, and so on). After the dilutions were completed, 100 pL of the standardized inocula (microorganisms of interest) were added to all wells of the microplate.The plates were sealed with plastic film and incubated for 24–48 hours at 36°C, at which point 50 µL of a 0.1% aqueous solution of TTC (2,3,5-triphenyltetrazolium chloride) was added to the wells, and the microplates were re-incubated for 3 hours at the aforementioned temperature. The MIC was defined as the lowest concentration of the extract capable of preventing the appearance of red coloration. The plates were prepared as described in Figures 2 and 3.

[0062]

[0050] Furthermore, inoculum preparation was carried out for the development of the minimum inhibitory concentration determination test. For this, the cultured cells are scraped and added to 4 mL of saline solution (0.85-0.9%), which is then appropriately diluted using spectrophotometry. The optical density was standardized at 625 nm for bacteria or 530 nm for yeasts, aiming for an absorbance between 0.08 and 0.1, targeting a concentration of 10 8 cells / mL (bacteria) or 10 6cells / mL (yeast), followed by dilution to final concentration according to specific standards (Figure 3). The MIC was defined as the lowest concentration capable of preventing the appearance of turbidity in the medium for Malassezia and a pink color for the other microorganisms.

[0063]

[0051] To define the minimum bactericidal concentration and minimum fungicidal concentration (MBC), inocula obtained from the MIC were used in petri dishes containing Mueller-Hinton agar for Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, and "Malassezia broth" for Malassezia. The MBC was defined as the lowest concentration of the compound that inactivates 99% of the inoculum.

[0064] Characterization of selected extracts by UHPLC-PDA-MS - Pomegranate peel extract

[0065]

[0052] Pomegranate peel extracts were centrifuged, diluted 10 times in water, filtered through a 0.45 µm nylon filter, and subsequently injected into ultra-high pressure liquid chromatography coupled to a photodiode array and mass spectrometry (UPLC-PDA-MS) (Acquity, Waters Co., Milford, MA, USA). The separation system was performed on an Acquity UPLC BEH C18 50 × 2.1 mm, 1.7 µm analytical column, and the mobile phases consisted of water (A) and acetonitrile (B), both acidified with 0.1% (v / v) acetic acid. The gradient used was: 0 min (98% A); 1.5 min (87% A); 1. 9 min (75% A); 3. 0 min (67% A); 3. 3 min (50% A); 3. 8 min (50% A); 4. 0 min (0% A); 6. 0 min (0% A); 7. 0 min (98% A); 10. 0 min (98% A). The column temperature was 30 °C, with a flow rate of 0.4 mL min⁻¹ and an injection volume of 4 µL. Absorbance was monitored between 210 and 400 nm, and ellagic acid (EA) quantification was performed at 370 nm.The compound was identified by comparing retention times, UV / MS spectra, and co-elution with an authentic AE standard. The results were expressed relative to the dry weight of pomegranate (mean ± standard deviation of the mean).

[0066] Rosemary extract

[0067]

[0053] Rosemary extracts were centrifuged, filtered through a 0.45 µm nylon filter, and subsequently injected into ultra-high pressure liquid chromatography coupled to a photodiode array and mass spectrometry (UPLC-PDA-MS) (Acquity, Waters Co., Milford, MA, USA). The separation system was carried out on an Acquity UPLC BEH C18 50 × 2.1 mm, 1.7 µm analytical column, and the mobile phases consisted of water (A) and acetonitrile (B), both acidified with 0.1% (v / v) acetic acid. The gradient used was that established by Pizani et al., 2024, doi: https: / / doi.org / 10.1016 / j.foodchem.2023.137540: 0 min (88% A); 0.5 min (85% A); 1.0 min (80% A); 1.2 min (77% A); 1.5 min (75% A); 1.7 min (73% A); 2.0 min (70% A); 2.3 min (67% A); 2.5 min (65% A); 3.0 min (60% A); 6.0 min (30% A); 7.0 min (88% A). The column temperature was 55 °C, with a flow rate of 0.6 mL min⁻¹ and an injection volume of 1 µL.Absorbance was monitored between 210 and 400 nm, and quantification of rosmarinic acid (RA) was performed at 330 nm. The compound was identified by comparing retention times, UV / MS spectra, and co-elution with an authentic RA standard. Results were expressed relative to the dry weight of rosemary (mean ± standard deviation of the mean).

[0068] Selection of the formulation for the production of liquid dressings

[0054] For the selection of the formulation for the production of the liquid dressing with the extracts, initially, different concentrations of polyvinylpyrrolidone (PVP), glycerol, starch, xanthan gum (GX), carboxymethylcellulose (CMC), ethanol and water were tested, as described in Tables 1 to 10.

[0069]

[0055] In the samples containing starch, the mass of this ingredient was hydrated to the desired final concentration (3 to 5%) and heated to 100 °C for 15 minutes, aiming at the gelation of the compound. Subsequently, the PVP mass was added to the systems, while still hot, under magnetic stirring for 10 minutes. After cooling the samples to room temperature for approximately 15 minutes, glycerol was added and the systems were homogenized for 2 minutes and left to rest for 5 minutes for subsequent evaluation of the visual aspect.

[0070]

[0056] For the starch-based formulations, the PVP mass was hydrated with an ethanol solution in ultrapure water and heated to 60°C for 10 minutes in a water bath. Subsequently, the samples were cooled to room temperature for approximately 15 minutes, and glycerol, carboxymethylcellulose, and xanthan gum were added. The formulations were homogenized for 2 minutes and left to stand for 5 minutes for subsequent visual assessment. The following were evaluated: presence of macroscopic phase separation, evident syneresis, spreadability (whether the sample was easy to spread on the skin), whether the sample ran off until drying, and approximate drying time.

[0071]

[0057] Furthermore, all the ingredients in the formulation, before being subjected to heating, are hydrated with water or different ethanol:water solutions. And the defined concentrations are presented in % m / v (mass of ingredient per volume of solution), however the percentages of water and ethanol are presented in v / v, and are always complementary, that is, in a sample with 5% ethanol is one in which all the solid ingredients were hydrated with a volume of solvent composed of 5% ethanol and 95% water.

[0072] Table 1. Formulations tested for the production of liquid dressings: variation in glycerol concentration in water.

[0073] n ~ PVP (% in Glycerol Solvent Formulation...

[0074] m / v) (% in m / v) (% in v / v)

[0075] Al 10 0 100% Water

[0076] A2 10 1 100% Water

[0077] Table 2. Formulations tested for the production of liquid dressings: variation in the concentration of glycerol and starch in water. A3 10 2 100% Water

[0078] Solvent

[0079]

[0080] Starch Formulation (% in

[0081]

[0082] ( % in m / v )

[0083] v / v) BI 10 3 3

[0084] THE Á 1 g 0 ° ' ua S B2 10 3 5

[0085] THE 1 0 ° ' gua S B3 10 5 3 Á 1 0 ° ' Water S B4 10 5 5

[0086] THE 1 0 ° ' gua S B5 10 7 3 Á 1 0 ° ' Water S B 6 10 7 5

[0087] THE Á 1 g 0 ° ' ua S

[0088] Table 3. Formulations tested for the production of liquid dressings: variation in PVP concentration in water. n~ PVP ( % Glycerol ( % Starch (% Solvent Formulation....

[0089] (in m / v) (in m / v) (in m / v) (% v / v) B2 10 3 5 100% Water B7 15 3 5 100% Water B8 20 3 5 100% Water

[0090] Table 4. Formulations tested for the production of liquid dressings: variation in glycerol concentration without starch.

[0091] ~ PVP ( % in Glycerol ( % Starch ( % Solvent Formulation m / v ) in m / v ) in m / v ) ( % in v / v )Cl 20 3 0 ^ l ^anol ( 50 % Water ) C2 20 5 0 ^ ( 5 l0 % E A4 a g n u°a >) C3 20 7 0 ^ ( 5 l0 % E A4 a g n Table 5. Formulations tested for the production of liquid dressings: variation in the proportion of ethanol.

[0092] ~ PVP (% in Glycerol (% Starch (% Solvent Formulation....

[0093] m / v) in m / v) in m / v) (% in v / v)

[0094] 30% Dl 20 7 0 Ethanol (70% water) D2 20 7 0 )° l

[0095] (50% E THE t a gn u o the 2 ) D3 20 7 0 J°

[0096] Ethan O the í Table 6. Formulations tested for the production of liquid dressings: variation in glycerol concentration in samples with carboxymethylcellulose.

[0097] Formulation PVP (% in Glycerol CMC (% in Solvent m / v) (% in m / v) m / v) (% in v / v) F1 20 3 1 50% Ethanol (50% Water) F2 20 5 1 50% Ethanol (50% Water) F3 20 7 1 50% Ethanol (50% Water)

[0098] Table 7. Formulations tested for the production of liquid dressings: variation in carboxymethylcellulose concentration in samples with PVP and glycerol.

[0099] n ~ PVP (% in Glycerol CMC (% in Solvent Formulation,.. o ,.,.. o ,.

[0100] m / v) (% in m / v) m / v) (% in v / v) G1 20 7 1 ™. E THE an °t

[0101]

[0102] (50% Water) no, c- 50% EthanolG2 2 0 7 2' 5(50% Water) G3 20 7 2 ^l E | an °) (50% Water) Table 8. Formulations tested for the production of liquid dressings: variation in xanthan gum concentration in samples with PVP, glycerol and 1.5% CMC

[0103] Glycerol

[0104] ", ~ PVP ( %, o CMC ( % GX ( % Solvent ( % Formulation,, ( % in.,.,., in m / v,, in m / v in m / v in v / vm / v)

[0105] 11 20 7 1, 5 0

[0106] (50% Water) 12 20 7 1.5 0.1 3 ° l ( 50 % E THE t a g n u o the 3 TQ ono IR no 5 0 % Ethanol 1 3 2 0 7 2' 5 ° ' 3 (50% Water) 14 20 7 1.5 0.5 3 ° l ( 50 % E THE t a g n u O the 3 ) 15 20 7 1, 5 1, 0 3 ° l T nO )

[0107]

[0108] (50% Water) Table 9. Formulations tested for the production of liquid dressings: variation in xanthan gum concentration in samples with PVP, glycerol and 3% CMC.

[0109] Glycerol

[0110] PVP ( %, o CMC ( % GX ( % Solvent ( % Formulation,, % in,,,,,, in m / v),, in m / v) in m / v) in v / v) m / v)

[0111]

[0112] J1 20 7 3 0

[0113] (50% Water) J2 20 7 3 0, 1 3 ° l

[0114] (50% E THE t a g n u O the 3 ) J3 20 7 3 0.3 ! ?THE E E aI Á ( 50 % Agua ) J4 20 7 3 0, 5 ( 50 % AguÁa ) JD5R 2 o n0 c 7 3 oi 1, n0 5 0 % Et -■ anol ( 50 % Water ) Table 10. Formulations tested for the production of liquid dressings: variation in the proportion of ethanol in samples with PVP, glycerol, CMC and xanthan gum PVP ( % Glycerol _,

[0115] ,, o CMC o GX (%

[0116] % Sun n ,

[0117] wind o % in Formulation in ( % in., in.,

[0118] in m / v) v / v) m / v) m / v) m / v)

[0119] Kl 20 7 3 1 100% Water K2 20 7 3 1 5 E t

[0120] the a

[0121] g n u O the 1 1) , 9 5 K4 20 7 3 12 5 % E t an°]

[0122] water ) ( 7 5 % K5 20 7 3 17 5 % E t year]

[0123] water ) ( 2 5 % K6 20 7 3 1 100% Ethanol

[0124] Production of liquid dressings with pomegranate peel and rosemary extracts.

[0125]

[0058] The best formulations, in terms of visual appearance, were those with 20% PVP, 7% glycerol, 3% CMC, 1% GX in 5% ethanol. This formulation was then used to produce liquid dressings with pomegranate peel and rosemary extracts. For the preparation of the dressings, the PVP mass (20% w / v) with the dry extracts (2–20 mg / mL) (concentrations selected from the minimum inhibitory concentration results) was hydrated with a 5% ethanol solution in ultrapure water and heated to 60°C for 10 minutes in a water bath. Subsequently, the samples were cooled to room temperature (for approximately 15 minutes) and added to glycerol (7% w / v), carboxymethylcellulose (3% w / v), and xanthan gum (1% w / v). The formulations were homogenized for 2 minutes and left to rest for 5 minutes for subsequent visual assessment.The following were evaluated: existence of macroscopic phase separation, evident syneresis, spreadability (whether the sample was easy to spread on the skin), whether the sample ran off until drying time and approximate drying time.

[0059] The following Examples present the results of the initial screening test of extracts from agro-industrial waste (Example 1), characterization test of the selected extracts by UHPLC-PDA-MS (Example 2), selection test of the formulation for the production of liquid dressings (Example 3), and production of liquid dressings with pomegranate peel and rosemary extracts (Example 4).

[0126] Example 1 - Initial screening test of extracts from agro-industrial residues

[0127]

[0060] The MIC and MBC results of the different extracts of agro-industrial waste are presented in Table 11. These results demonstrated that the extracts with the best antimicrobial activities were, in increasing order of importance: mango leaf, lemon peel, coffee grounds, guava leaf, rosemary and pomegranate peel.

[0128]

[0061] The mango leaf extract showed inhibitory activity only against S. epidermidis, with a MIC of 2000 µg / mL. The lemon peel extract showed inhibitory activity only against S. aureus, with a MIC of 2000 µg / mL. In both cases, the activities were only bacteriostatic, as verified by the MBC data.

[0129]

[0062] The coffee grounds extract, in turn, showed inhibitory activity only against S. epidermidis, with a MIC of 250 µg / mL and MBC of 2000 µg / mL.

[0130]

[0063] Guava leaf, rosemary and pomegranate peel extracts were the ones with the best results, showing inhibitory activity against a greater number of microorganisms.

[0131]

[0064] Pomegranate peel and guava leaf extracts showed inhibitory activity against the same microorganisms: S. aureus, S. epidermidis, and Malassezia; however, the MIC of the pomegranate peel extract was lower than the MIC shown by the guava leaf extract, indicating greater inhibitory activity.

[0132]

[0065] Rosemary has shown activity against S. aureus and S. epidermidis, with a MIC of 500 µg / mL; however, in this case, the activities shown were not only bacteriostatic, but bactericidal, as demonstrated by the MBC results.

[0133]

[0066] Considering the greater activity of pomegranate peel extracts compared to guava leaf extracts and the complementary bactericidal action of rosemary extracts, both extracts (pomegranate peel and rosemary) were selected for the development of this research.

[0134] Table 11 - Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of extracts from different agro-industrial residues (in µg / mL).

[0135] Microorganism

[0136] Pseudomonas residue Staphylococcus Staphylococcus Malassezia agroindustria aeruginosa aureus epidermidis

[0137] CMI CBM CMI CBM CMI CBM CMI CBM

[0138] Bark

[0139] orange

[0140] Bark

[0141] manga

[0142] Apple peel * * * * * * * * Grape skin * * * * * * * * Leaf of

[0143] ■ * * * 2000

[0144] manga

[0145] Coffee husk * * * * * * * * Coffee husk

[0146] ■ 2000

[0147] lemon

[0148] Pomegranate peel * * 500 * 250 1000 31 * Leaf of

[0149] * * 2000 * 1000 2000 500 * guava

[0150] Coffee grounds * * * * 250 2000 * * Seed of

[0151] melon

[0152] Rosemary * * 500 2000 500 500 * *

[0153] * Concentration greater than 2000 µg / mL

[0154] Example 2 - Characterization test of selected extracts by UHPLC-PDA-MS

[0155]

[0067] The two extracts selected from the antimicrobial activity assays were characterized by UHPLC-PDA-MS and the chromatograms obtained are shown in Figures 4 and 7.

[0156]

[0068] It is known that one of the main phenolic compounds commonly found in rosemary samples is Rosmarinic Acid (RA), widely recognized for its antioxidant activity and a broad spectrum of other biological and pharmacological activities (Pizani et al., 2024, doi: https: / / doi.org / 10.1016 / j.foodchem.2023.137540).

[0157]

[0069] In order to identify and quantify this important compound in the rosemary extract produced in this research, the same method used to analyze the sample was applied with a pure AR standard, which showed a retention time of 1.38 min. In addition, a calibration curve was obtained from the analysis of known concentrations of the standard (Figure 3). From the comparison of the standard analyses (RT, UV and MS spectra - illustrated in Figure 2), AR was identified as responsible for the peak with a retention time of 1.389 min, illustrated in Figure 4. From the area of ​​this peak (triplicate: 414950, 416354, 410660), it was possible to conclude that the concentration of rosmarinic acid in the extract produced was approximately 209 pg / mL.

[0158]

[0070] In the case of pomegranate peel extract, the compound of interest selected was ellagic acid, a compound known for its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties (Hitl et al., 2021, doi: https: / / doi.org / 10.1055 / a-1301-8648). Similar to the protocol applied to the rosemary extract, the pure ellagic acid standard was also analyzed and showed a retention time of approximately 2.85 min. From the extract data and the standard data, it was found that the peak corresponding to the compound of interest was the peak highlighted in Figure 7, which, in addition to showing the same retention time as the standard, presented UV and MS spectra (Figure 8A and Figure 8B) compatible with Ellagic Acid. Based on the area of ​​that peak (triplicate: 18082, 21867, 19655), the 10x dilution, and the calibration curve, it was possible to calculate that the ellagic acid concentration of the sample was approximately 174 µg / mL.

[0159]

[0071] Following the selection and characterization of the extracts, the next step in the research consisted of selecting an interesting formulation for the production of liquid dressings, for their subsequent incorporation. Example 3 – Formulation selection test for the production of liquid dressings

[0160]

[0072] The three main ingredients of a liquid dressing are: (i) a polymer responsible for forming the "film" on the skin (in this case PVP), (ii) a plasticizing agent (in this case glycerol) and (iii) a solvent (water). In this sense, the first step of this stage of the present invention consisted of fixing a concentration of 10% PVP and varying the concentration of glycerol from 0 to 2% to understand the effects of the interactions between the two ingredients.

[0161]

[0073] Pure water was initially used as a solvent, considering it ideal for application to wounds, as it does not cause intense pain, discomfort, or risks to the health of individuals. As described in Table 12, the first three formulations tested (A1, A2, and A3) had a very liquid appearance, which is undesirable for the ideal formulation.

[0162]

[0074] For proper use of the liquid dressing, the product must have a firmer consistency (although liquid, as the name itself suggests), so that the material does not run off and come out of the wound area before the drying and film formation process. In addition, considering the characteristics of the ingredients used, the drying process was excessively slow, not allowing the PVP film to form.

[0163] Table 12. Formulations tested for the production of liquid dressings: variation in glycerol concentration in water. n~ PVP (% in Glycerol Solvent Visual aspect Formulation,., o ,.,.

[0164] m / v) (% in m / v) (% in v / v)

[0165] Al 10 0 100% Water ^liquid little

[0166]

[0167] VISCOUS A2 10 1 100% Water Slightly viscous liquid A3 10 2 100% Water Slightly viscous liquid

[0168]

[0075] Based on these results, two measures were adopted: increasing the glycerol concentration, for a possible increase in the product's viscosity, and incorporating starch into the system, with its drying potential. The choice of this ingredient is justified by its low toxicity, low cost, and great potential for large-scale application. Initially, the concentrations described in Table 13 were tested and, as reported, all systems presented a cloudy appearance, more viscous than the formulations described in Table 12, but with macroscopically evident phase separation after 2 minutes at rest at room temperature, indicating inadequate starch gelation. This heterogeneous appearance with phase separation (indicated by the red arrow) is illustrated in Figure 10.

[0169]

[0076] Although these samples showed better viscosity, they still exhibited excessive flow and unsatisfactory drying time (greater than 15 min), which is undesirable for the product. Furthermore, the phase separation process presented, besides potentially reducing the product's acceptance among consumers, also compromises the effective action of starch as a drying agent. Table 13. Formulations tested for the production of liquid dressings: variation in glycerol and starch concentration in water PVP Glycerol Starch Solvent Appearance Formulation ( % in ( % in ( % in ( % in visual m / v) m / v) m / v) v / v)

[0170] 100% heterogeneous

[0171] B1 10 3 3 100% Water, Heterogeneous with evident phase separation

[0172] evident phases Heterogeneous 100%

[0173] B2 10 3 5 100% Water Heterogeneous with evident phase separation

[0174] evident phases Heterogeneous 100%

[0175] B3 10 5 3 100% Water, Heterogeneous with evident phase separation

[0176] evident phases Heterogeneous 100%

[0177] B4 10 5 5 100% Water Heterogeneous with evident phase separation

[0178] evident phases Heterogeneous 100%

[0179] B5 10 7 3 100% Water, Heterogeneous with evident phase separation

[0180] evident phases Heterogeneous 100%

[0181] B6 10 7 5 100% Water Heterogeneous with evident phase separation

[0182] evident phases

[0183]

[0077] Given the observed effects, the next step consisted of increasing the concentration of PVP, which was beneficial to the systems (Table 14), which began to exhibit greater viscosity (although they still flowed excessively after application) and a more effective film formation. However, the phase separation of the starch with the system at rest was still evident, which, as mentioned earlier, is undesirable for the product.

[0184] Table 14. Formulations tested for the production of liquid dressings: variation in PVP concentration in water.

[0185] PVP Glycerol Starch,, o Aspect SolVCntC ( %

[0186] Formulation ( % in ( % in ( % in., visual

[0187] ,.,.,. in v / v

[0188] m / v) m / v) m / v)

[0189] Slightly viscous liquid and B2 10 3 5 100% Water Slightly viscous and heterogeneous liquid with evident phase separation Viscous and heterogeneous liquid B7 15 3 5 100% Water with evident phase separation Very viscous and heterogeneous liquid B8 20 3 5 100% Water with evident phase separation

[0190]

[0078] Considering the unsatisfactory behavior of the starch in the system, the next step in the research involved removing the starch from the formulation and attempting to replace the solvent, pure water, with a 50% ethanol solution. Considering the characteristics of ethanol, the development to be tested was that the faster evaporation of the solvent could compensate for the low viscosity of the sample, allowing for the proper formation of the PVP film. The results were more satisfactory (Table 15), and the samples did, in fact, dry in less than 10 minutes. However, the viscosity of the systems was still low. Furthermore, the films presented a brittle appearance for samples with 3% and 5% glycerol, and a better appearance for samples with 7% glycerol.

[0191]

[0079] For this reason, formulation C3, described in Table 15, was selected for the subsequent stage of testing, which consisted of varying the percentage of ethanol in the sample, as described in Table 16. Among the samples tested, formulation D2 remained the best option, with the sample with 100% ethanol proving to be very liquid and, after drying, the film formed was very brittle, "cracking" on the surface, and the sample with 30% ethanol showed slower drying. The visual aspect of samples that formed a brittle film with a cracking surface is shown in Figure 11.

[0192] Table 15. Formulations tested for the production of liquid dressings: variation of glycerol concentration without starch PVP Glycerol Starch Solvent Appearance Formulation ( % in ( % in ( % in ( % in visual m / v) m / v) m / v) v / v)

[0193] 50% Liquid C1 20 3 0 50% ethanol (50% water) Homogeneous liquid, low viscosity - resulting in brittle films 50% Liquid ethanol, homogeneous (50% low viscosity C2 20 5 0 water) - viscous - resulting in brittle films 50% Liquid ethanol, homogeneous (50% low viscosity C3 20 7 0 water) - viscous;

[0194] resulting in films that are not very fragile.

[0195] Table 16. Formulations tested for the production of liquid dressings: variation in the proportion of ethanol PVP Glycerol Starch Solvent Appearance Formulation ( % in ( % in ( % in ( % in visual m / v) m / v) m / v) v / v)

[0196] Homogeneous liquid 30% more s Dl 20 7 0 viscous -

[0197]

[0198] (70% water-producing) slightly brittle films Homogeneous liquid 50% slightly viscous D2 20 7 0 ethanol (50% viscous - (50% water-producing) slightly brittle films Homogeneous liquid slightly viscous 100% - D3 20 7

[0199]

[0200] Ethanol resulting in very brittle films.

[0201]

[0080] Considering that the sample's appearance in terms of viscosity and drying time was still inadequate, the next test consisted of incorporating different concentrations of carboxymethylcellulose (Table 17) into the samples with the previously selected formulation. Among the samples tested, G2 and G3 showed the best appearance, with drying times and viscosities that appeared more adequate. In this sense, these two formulations were selected for the addition of xanthan gum, aiming for a greater and more effective increase in viscosity, so that, after the addition of the dressing, the product would remain in the applied area until drying.

[0202]

[0081] Among all the formulations described in Tables 18 and 19, formulation J5 presented the best visual aspect, with a higher viscosity and a more suitable and less brittle film appearance after drying.

[0203]

[0082] One problem, however, was that the percentage of ethanol in the formulation remained high. Considering its application to wounds, the presence of 50% ethanol in the formulation's solvent would be potentially uncomfortable at the time of application, possibly causing a burning sensation in the area until drying and film formation. In this sense, the next step consisted of varying the percentage of ethanol in the samples, as described in Table 20.

[0083] The results showed that reducing the percentage of ethanol to 5% was not detrimental to the formulation, which presented a drying time of approximately 5 min on the skin. During drying, due to the high viscosity of the systems, the dressing remained in the applied area, thus presenting the desirable characteristics of the product.

[0204]

[0084] Formulation K2 (visual aspects shown in Figures 12A, 12B and 12C) was selected for the production of dressings with natural extracts.

[0205] Table 17. Formulations tested for the production of liquid dressings: variation in the concentration of carboxymethylcellulose and in samples with PVP and glycerol.

[0206] PVP (% Glycerol CMC (% n , o Aspect „, o Solvent % Formulation in (% in, visual

[0207] ,.,.,. in v / vm / v) m / v) m / v)

[0208] 50% Ethanol Liquid G1 20 7 1 (50% water) Homogeneous viscous 50% Ethanol Liquid (50% water) Homogeneous G2 20 7 1.5 50% Ethanol (50% water) Homogeneous liquid very viscous 50% Ethanol Liquid n (50% water) homogeneous G5 20 7 3

[0209] very vis coso

[0210] Table 18. Formulations tested for the production of liquid dressings: variation of xanthan gum concentration in samples with PVP, glycerol and 1.5% CMC. PVP Glycerol CMC GX (% Solvent Appearance Formulation (% in (% in (% in (% in visual m / v) m / v) m / v) m / v) v / v)

[0211] 50% Liquid -1 homogeneous ethanol I1 20 7 1.5 0 50% ethanol (50% water) Very viscous homogeneous liquid 50% Liquid TT homogeneous ethanol I2 20 7 1.5 0.1 50% ethanol (50% water) Very viscous homogeneous liquid 50% Liquid -1 homogeneous ethanol I3 20 7 1.5 0.3

[0212] (50% very water) viscous 50% Liquid T „ r homogeneous ethanol I4 20 7 1.5 0.5

[0213] (50% very watery) viscous 50% Appearance I5 20 7 1.5 1.0 Pasty appearance

[0214]

[0215] (50% homogeneous water)

[0216] Table 19. Formulations tested for the production of liquid dressings: variation in xanthan gum concentration in samples with PVP, glycerol and 3% CMC.

[0217] PVP CMC GX Visual aspect., ~ ( % Glycerin ( % ( % Solvent

[0218] Formul aça,

[0219] in 1 ( % in in in and ( % in

[0220] m / vm / v) m / vm / vv / v)

[0221] 50% Liquid homogeneous ethanol very J1 20 7 3 0

[0222] (50% vis coso water)

[0223] 50% Liquid homogeneous ethanol very J2 20 7 3 0.1

[0224] (50% viscous water) 50% Liquid Q homogeneous ethanol very

[0225]

[0226] (50% vis coso water)

[0227] 50% Liquid J4 20 7 3 0.5 50% ethanol (50% water) Very viscous homogeneous liquid

[0228] (50% vis coso water)

[0229] J5 20 7 3 1.0 50% ethanol (50% water) Homogeneous pasty / gel-like appearance

[0230] (50% of the homogeneous water)

[0231] Table 20. Formulations tested for the production of liquid dressings: variation in the proportion of ethanol in samples with PVP, glycerol, CMC and xanthan gum.

[0232] PVP CMC GX Visual appearance „, ( % Glycer ( % ( % Solvent

[0233] Formulaç

[0234] in 1 n

[0235] ( % in in in ( % in

[0236] m / vm / v) m / vm / vv / v)

[0237] K1 20 7 3 1 100% Water Homogeneous liquid, very viscous K2 20 7 3 1 5% Ethanol (95% water) Homogeneous pasty / gel-like appearance 25% Appearance. Ethanol pasty / gel-like if ic

[0238]

[0239] (75% homogeneous water)

[0240] K5 20 7 3 1 75% Ethanol (25% water) Highly viscous homogeneous liquid

[0241] (25% viscous water)

[0242] 100% Liquid K6 20 7 3 1 homogeneous very Ethanol

[0243] Example 4 - Production of liquid dressings with pomegranate peel and rosemary extracts

[0244]

[0085] The selected formulation was then used to produce liquid dressings with pomegranate peel and rosemary extracts. The concentrations of dry extract added were: (i) 2 mg / mL, (ii) 10 mg / mL and (iii) 20 mg / mL, the lowest being calculated based on the minimum bactericidal concentration of rosemary extract against S. aureus and the highest concentration calculated to be ten times greater than the lowest concentration. The visual aspects of the samples at different stages of the dressing production process are available in Figures 13A, 13B, 13C, 13D and 13E. It is possible to verify that the dressings presented a pasty / gel-like appearance at the time of application and, approximately 5 minutes after application, presented a film-like appearance on the skin, that is, presenting the desirable characteristics of liquid, homogeneous and viscous, with rapid drying after application.During the drying process, the samples showed good adhesion to the surface and did not run.

Claims

CLAIMS 1. LIQUID DRESSING COMPOSITION, characterized by comprising: Polyvinylpyrrolidone (PVP) between 10 and 20% (w / v), preferably 20%; - Glycerol between 1 and 7% (w / v), preferably 7%; Carboxymethylcellulose (CMC) between 1.5 and 3% (w / v), preferably 3%; - xanthan gum (GX) between 0.1 and 1%, preferably 1%; - Water between 90 and 100% (v / v), preferably 95%; - Ethanol between 1 and 10% (v / v), preferably 5%; - pomegranate peel extract at 2 to 20 mg / mL; and - Rosemary extract at 2 to 20 mg / mL.

2. A dressing, characterized by comprising the composition as defined in claim 1, being homogeneous, viscous, and quick-drying after application.

3. PROCESS FOR PRODUCING LIQUID DRESSINGS, characterized by comprising the following steps: (i) Hydrate the PVP mass and the dried pomegranate peel and rosemary extracts with a 5% ethanol solution in ultra-purified water; (ii) Heat the composition from step (i) to 60°C for 10 minutes in a water bath; (iii) Cool the composition from step (ii) to room temperature for approximately 15 minutes; (iv) Add 7% w / v glycerol, 3% w / v carboxymethylcellulose, and 1% w / v xanthan gum to the composition from step (iii), homogenize for 2 minutes, and let stand for 5 minutes.

4. USE OF THE LIQUID DRESSING COMPOSITION, as defined in claim 1, characterized by being for the manufacture of a liquid dressing for the treatment of bacterial infections caused by Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Malassezia.

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