Uses of compositions containing cyclic oligosaccharides with antibiofilm and / or antifungal activity

Abstract

The present invention consists of the use of cyclic oligosaccharides as modulators of the activity of antiseptic active ingredients, causing a synergistic effect in antimicrobial compositions; more specifically, the present invention presents the ability of cyclic oligosaccharides to alter or modulate the spectrum of antimicrobial activity of an antiseptic active ingredient, enabling efficacy against microorganisms against which the active ingredient is not effective in its isolated form or increasing its efficacy against fungi, resistant microorganisms, such as resistant fungi, and microorganism biofilms. The present invention also presents the novelty of a composition that hinders the development of resistant microorganisms and / or eliminates resistant microorganisms, thanks to the specific characteristic of the cyclic oligosaccharide and the slow and continuous release of the antiseptic active ingredient. For resistant microorganism biofilms, the prolonged antiseptic action obtained has a significant impact on combating the complex defences created by biofilms.

Description

USES OF COMPOSITION CONTAINING CYCLIC OLIGOSACCHARIDES WITH ANTIBIOFILM AND / OR ANTIFUNGAL ACTIVITY TECHNICAL DOMINION

[0001] This disclosure refers to the use of an inclusion compound, also called an inclusion complex, with antibiofilm and / or antifungal activity, applicable in therapeutic, agronomic, and food contexts, as well as hygiene, disinfection, and / or sanitization processes. BACKGROUND

[0002] Antimicrobial resistance (AMR) is among the top global threats to health and human development. The World Health Organization calls for urgent multisectoral action to achieve the Sustainable Development Goals (SDGs) and considers multidrug-resistant microorganisms (or "superbugs") to be one of the greatest challenges humanity will face.

[0003] This threat could become a new pandemic, potentially more deadly than COVID-19. Associated with five million deaths annually, antimicrobial resistance (AMR) becomes the third leading underlying cause of death worldwide.

[0004] The overuse, misuse, and underuse of several classes of antibiotics, as well as their intended elimination or inadequate treatment in various sectors, including agriculture, veterinary medicine, and healthcare, has led to an increase in antibiotic resistance among microorganisms. The need to develop new generations of antibiotics has economic, social, and medical consequences, including increased mortality rates and financial burdens.

[0005] Drug-resistant microorganisms have been declared a matter of global concern by the Centers for Disease Control and Prevention (CDC), the Infection Disease Society of America (Infectious Diseases Society of America), the World Economic Forum (World Economic Forum), and the World Health Organization (WHO).

[0006] The common actions of drugs against bacteria are: inhibition of deoxyribonucleic acid (DNA) replication, translational activity, and cell wall synthesis. Once the antibiotic is eliminated regularly, the mutation will continue to exist and transmit resistance through vertical and horizontal transfer. Microorganisms' resistance mechanisms include alternating membrane permeability, excess drug efflux, and enhanced efflux. genetic modifications that affect or protect target areas, deactivation of the drug molecule by covalent binding, transmission of resistance by plasmids and the development of biofilms.

[0007] A biofilm is a complex, highly dynamic microbial ecosystem that acts in a coordinated manner, attached to biotic and / or abiotic surfaces or suspended in solution. The cells may or may not be surrounded by an exopolymer matrix and may be formed from a single or multiple species. It is important to note that microbial biofilms are produced by pure cultures of bacteria and by combinations of microorganisms, which may include fungi, protozoa, and algae (SCHNEIDER, RP Biofilmes Microbianos. Microbiologia em Foco, n 2, vol 1, p 4–12, 2007).

[0008] Bacteria and fungi form biofilms as part of their survival mechanisms, and therefore, biofilms are ubiquitous in nature. Although certain constituents are common to all biofilms, the host's contribution to the microorganisms, such as immunological components and physical conditions, impacts this structure. Among the various functions of biofilms, microorganisms use them for communication through the release of substances within this structure, a process called density-dependent communication between microorganisms (quorum sensing) (Pena RT, Blasco L, Ambroa A, González-Pedrajo B, Fernández-García L, López M, Blériot I, Bou G, Garcia-Contreras R, Wood TK and Tomás M (2019) Relationship Between Quorum Sensing and Secretion Systems Front Microbiol. 10:1100).

[0009] Biofilms protect microorganisms, making them a resistant source of contamination. This leads to continued unresponsiveness to removal treatments such as pH changes, ultraviolet radiation, osmotic pressure changes, scraping, and antimicrobial agents. Within these biofilms, only nutrients enter and wastes exit, protecting them from the action of antibiotics, antifungals, and some components of the immune system (when there is contamination in the animal organism). As a result, these microorganisms become even more resistant to antibiotics or surface disinfectants (Ramage G, Mowat E, Jones B, Williams C, Lopez-Ribot J. Our current understanding of fungal biofilms. Crit Rev Microbiol. 2009;35(4):340-55). The collaboration within the microcommunity of a biofilm structure contributes to substrate change, the flow of metabolic products, and the elimination of metabolic waste.This microcommunity is organized to ensure that a minimal bacterial structure survives in anaerobic environments (anaerobic digestion) and when organic materials break down into CH4 and CO2. These surviving bacteria are considered the most resilient, as they resist attack by biofilms and, for a period, close themselves off from receiving food and oxygen.

[0010] The biofilm offers a favorable environment for the establishment of a syntrophic association, which is an affiliation of two or more metabolically distinct bacteria, which exchange substrates for their energy needs.

[0011] Biofilms pose a serious public health problem due to the potential for these microorganisms to cause infections in patients by establishing themselves on internal medical devices. Their organized structure helps reduce their susceptibility to antiseptic active ingredients, resulting in greater survival and persistence on surfaces, and increasing the risk of cross-contamination.

[0012] In hospitals, biofilm formation on surgical equipment and surfaces in general makes it difficult to maintain a sterile environment. Studies indicate that biofilms also tend to form more quickly on hydrophobic materials such as Teflon and other plastics than on glass and metal (Xiaobo Liu, Bo Tang, Qjuya Gu, Xiaobin Yu, "Elimination of the formation of biofilm in industrial pipes using enzyme cleaning technique," Methods X, vol. 1, p. 130–136, 2014).

[0013] Biofilms are estimated to cause around 1% of gross domestic product (GDP) in industrialized countries. Microbial biofilm formation affects everything from building pipes to supertankers, generating high costs associated with periodic maintenance to remove and treat the affected area. In manufacturing industries, the main source of damage is heat exchangers, as their rapid formation increases their resistance to heat transfer, as a thick layer of biofilm impedes the normal exchange process. Water supply system pipes also suffer from biofilm formation, directly impacting human health. It is very difficult to reach internal structures and properly sanitize them. Humidity and lack of light contribute to the increased proliferation of resistant microorganisms.

[0014] Considering that biofilm structure formation depends on the presence of flagella or fimbriae, the exopolysaccharide production capacity, and the cell's hydrophobicity, some microorganisms are more likely to form biofilms than others. Among the many microorganisms, such as various fungi and bacteria, some are more relevant in biofilm contamination in hospital settings, such as Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus viridans, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and mycobacteria. These microorganisms can come from the skin of patients, healthcare professionals, water, and environmental sources.

[0015] Even in individuals with excellent cellular and humoral immune responses, biofilm infections are rarely resolved by host defense mechanisms because antibodies are not effective in killing microorganisms within biofilms and can cause damage to immune complexes in surrounding tissues (Cochrane DMG Immune response to bacterial biofilms. Med Microbiol J 1988;27:255).

[0016] Still in biofilm structures, whose complexity of interactions between different types of microorganisms creates a barrier that is highly difficult to access, there are few alternatives to effective antiseptic active ingredients. Eliminating microorganisms located in the deepest layers of biofilms is the biggest challenge in combating them.

[0017] Among the different classes of microorganisms, fungi are a major concern, and society is finding it difficult to treat diseases related to them, especially in patients with weakened immune systems. One of the challenges is late diagnosis and the ineffectiveness of existing antifungals, such as fluconazole, significantly increasing the mortality rate of people infected with fungi.

[0018] The same fungus can cause different diseases depending on the organism it inhabits. A single species can include distinct species with varying levels of drug resistance, as is the case with Candida parapsilosis, reclassified into three species: C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis. All three can be found on the hands of medical staff in hospitals, resulting in infections associated with the handling of catheters and other devices commonly used in intensive care units.

[0019] The virulence of fungi and their ability to cause infection and drug resistance are not obvious. Fungi possess great genotypic plasticity and a high degree of adaptability to different environments. For example, acute and chronic fungal pneumonias are often undertreated, often due to delayed diagnosis.

[0020] The World Health Organization (WHO) has released a list of 19 fungi that exhibit pathogenic characteristics in humans and have demonstrated resistance to conventional treatments, resulting in high mortality rates. This rate is estimated to be around 1.7 million deaths annually and over 150 million serious infections worldwide. In most cases, fungal diseases appear in people who are already ill from other causes and are vulnerable to infections due to weakened immune systems, such as those with cancer, acquired immunodeficiency syndrome (AIDS), or respiratory diseases such as tuberculosis and COVID-19.

[0021] Among the list presented by the WHO, the fungi Aspergillus fuminatus, Cryptococcus neoformans, Candida albicans, and Candida auris are in the critical priority group. The fungus Aspergillus fuminatus produces spores that spread through the air, can threaten the lung health of people with compromised immune systems, and is present, for example, in animal feed. The fungus Cryptococcus neoformans is a leading cause of disease in patients with the human immunodeficiency virus (HIV / AIDS) and kills at least 180,000 people annually.

[0022] Species of the genus Candida spp. are known to cause diseases in humans, such as candidiasis, and are common in hospital settings. Candida albicans (C. albicans) is commonly Found in the human intestine, it can cause invasive infections in immunocompromised individuals, potentially leading to asthma-like conditions, pulmonary fibrosis, or non-cancerous tumors. Most manifestations of candidiasis are associated with the formation of Candida biofilms on surfaces and are also associated with mucosal and systemic infections.

[0023] Candida sp. biofilms share several properties with bacterial biofilms, as they have the ability to adhere and form biofilms with structural heterogeneity and typical microcolony and water channel architecture similar to bacterial biofilms. C. albicans biofilm formation has three distinct developmental phases: early, intermediate, and mature. Antifungal drug resistance is rapidly becoming a major problem. The main genes contributing to drug resistance in C. albicans are the CDR genes (CDR 1 and CDR 2) and the MDR genes. These genes have been shown to be upregulated during biofilm formation and development (Khosravi Rad K, Falahati M, Roudbary M, Farahyar S, Nami S. Overexpression of MDR-1 and CDR-2 genes in fluconazole resistance of Candida albicans isolated from patients with vulvovaginal candidiasis. Curr Med Mycol. 2016).

[0024] According to a warning from the Brazilian Health Regulatory Agency (Anvisa), some strains of Candida auris (C. auris) are resistant to polyenes, azoles, and echinocandins, the three main classes of antifungal drugs. Furthermore, these strains are resistant to most disinfectants used in hospitals and can persist in the environment for weeks or months. Anvisa reports that 39% of hospital mortality in Brazil is associated with the C. auris fungus, which has led to the deaths of between 30% and 60% of hospitalized patients.

[0025] The first record of infection by this fungus was made in 2009, in the ear of a patient in Japan. In the last decade, the microorganism has spread to more than 30 countries and infected more than 4,700 people (Chen, J., Tian, ​​S., Han, X. et al. Is the superbug fungus really so scary? A systematic review and meta-analysis of global epidemiology and mortality of Candida auris. BMC Infect Dis 20, 827 (2020), (Calvo B, Melo AS, Perozo-Mena A, Hernandez M, Francisco EC, Hagen F, Meis JF, Colombo AL. First report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia. J Infect. 2016 Oct;73(4):369-74).

[0026] WHO encourages countries to follow a stepwise approach, starting with strengthening their laboratory and surveillance capacities for fungal and bacterial diseases, and ensuring equitable access to existing quality therapies and diagnostics.

[0027] Because biofilms contaminate industrial piping, dental water lines, catheters, ventilators, and medical implants, they act as a source of disease for humans, animals, and plants. Given this, it's not surprising that a staggering number of chronic bacterial and fungal infections involve biofilms, which are not easily eradicated by conventional antibiotic therapy.

[0028] The three main drugs used to treat fungi are fluconazole, amphotericin B, and drugs belonging to the echinocandin group. However, these medications have side effects. Fluconazole is generally well tolerated, but there are reports of severe cases of hepatotoxicity (namely, necrosis, hepatitis, cholestasis, and fulminant hepatic failure) and death, with the most common symptoms being abdominal pain, nausea, vomiting, constipation, and flatulence. The most common side effects of amphotericin B are chills, tremors, headache, seizures, tachycardia, arrhythmia, hyper or hypotension, increased serum creatinine, pyrexia, hypokalemia, nausea, vomiting, and abdominal pain.Echinocandins have low toxicity compared to other antifungals; however, their intravenous administration presents reactions such as fever, chills, hives and / or rash, hypokalemia, anemia, flushing, nausea, vomiting, diarrhea, and phlebitis.

[0029] The types of fungi considered pathogenic are those that cause systemic mycoses, such as fungi of the genera Cryptococcus, Histoplasma and Coccidioides; opportunistic mycoses, such as fungi of the genera Candida, Aspergillus and Penicillium; and those that cause cutaneous and subcutaneous mycoses, such as fungi of the genera Sporothrix, Trichophyton, Trichosporon, Epidermophyton, Microsporum, Fusarium, Fonsecaea, Cladosporium, Exophiala and Malassezia.

[0030] Among the fungi that cause pathogenic diseases in humans, Aspergillus fumigatus is one of the most dangerous, as it primarily affects the lungs, as well as Histoplasma capsulatum and Penicillium marneffei, which, in addition to the lungs, can affect vital areas such as the liver and kidneys, especially in HIV-positive individuals with weakened immunity, potentially leading to death. Another fungus that survives in only 20% of infected individuals is Lomentospora prolificans.

[0031] Species of the genus Candida spp. are known to cause diseases such as candidiasis and are common in hospital settings. Candida albicans is commonly found in the human intestine but can cause invasive infections in immunocompromised individuals, potentially leading to conditions similar to asthma, pulmonary fibrosis, or non-cancerous tumors. The WHO suggests that overcrowding and a lack of resources for infection control practices, such as prolonged use of personal protective equipment due to lack of availability, could create fertile ground for microorganisms such as C. auris to spread, colonize invasive devices, and trigger healthcare-associated infections.

[0032] Fungal or mycotic skin infections in humans can be superficial or deep. The most common agents involved are the Microsporum and Trychophyton species. Scalp mycoses, such as Tinea capitis, affect the scalp and hair, causing scaling and patchy alopecia. For body mycoses, diseases related to fungi of the genera Sporothrix, Trichophyton, Trichosporon, and Epidermophyton are known. Microsporum, Fusarium, Fonsecaea, Cladosporium, Exophiala, and Malassezia. These diseases require prolonged treatment, with topical or even systemic medication in more severe cases.

[0033] Among the most common fungal diseases in animals are candidiasis, the same genus of fungus present in the human microbiota (Candida spp.); dermatophytosis, caused by the fungi Microsporum spp., Trichophyton spp., and Epidermophyton spp.; and malasseziosis, a disease associated with the fungus Malassezia spp. In particular, malasseziosis causes hair loss, severe itching, skin hyperpigmentation, and redness, and this fungus is almost always accompanied by bacteria or an allergic reaction (Nobre, M.; Meireles, M.; Gaspar, LF; Pereira, D.; Schramm, R.; Schuch, LF; Souza, L; Souza, L, Malassezia pachydermatis and other infectious agents in external otitis and dermatitis in dogs, Ciência Rural, 28(3), 2008, p. 447-452.).

[0034] The cure for these diseases usually requires a long period of treatment. The veterinary drugs used are sold in the form of ointments, sprays, creams, soaps, and specific shampoos, and the choice of application method is usually based on the size and location of the lesion or the animal's age. For systemic infections, the animal often requires oral or injectable dosing.

[0035] Animal feed is one of the main sources of animal nutrition; however, it can also be subject to microbial contamination, primarily by fungi that produce mycotoxins that pose health risks to the animal, depending on the amount of contaminated feed ingested, the species, and the animal's life stage. For this reason, feed factories for these segments pay close attention to quality throughout the entire process, from the receipt and storage of raw materials to the production, transportation, and final storage of the feed. The basis of animal feed is obtained from plant-based raw materials, such as cereals and grains, which require special attention due to the high risk of fungal contamination, leading to the presence of mycotoxins.

[0036] Mycotoxin contamination of feed causes various problems to feed quality, such as changes in organoleptic characteristics and a reduction in the nutrients available in the animal's diet. Consequently, these changes can negatively impact and affect animal performance.

[0037] Bovine mastitis is an inflammation of the mammary gland that is the most important disease associated with dairy farming worldwide. It is estimated to cause annual losses of US$1.8 billion in the United States alone (Souza GN et al., Mastitis, Embrapa Dairy Cattle, 2021. Accessed on: April 5, 2023). Mastitis is associated with contamination by colonies of microorganisms in the udder region of dairy cows. Research shows that udder contamination is associated with milking equipment used contaminated with non-aureus staphylococcus, Staphylococcus epidermidis, and especially biofilms, indicating contagious transmission between cattle. Therefore, one way to avoid cross-contamination is to properly clean milking equipment. These equipments should be cleaned using products that are easy to apply and remove, act quickly, and do not contaminate the milk (Almeida, LM; De Almeida, MZP; Mendonça, CLD; Mamizuka, EM Comparative analysis of agr groups and virulence genes among subclinical and clinical mastitis Staphylococcus aureus isolates from sheep flocks of the Northeast of Brazil. Braz J Microbiol. 44, 2013, 493-498).

[0038] Regarding diseases in large animals, data indicate that the average incidence of hoof disease in beef cattle is 5% to 20% per year, and in dairy cattle, it is 15% to 35%. In horses, it reaches around 20%. Treatment of hoof diseases is often done through footbaths.

[0039] One way to prevent fungal growth in animal feed is to use antifungals as preservatives, increasing the shelf life of products. Currently, the most commonly used active ingredients for this purpose are citric acid, propionic acid, sorbic acid, and calcium propionate, used individually or in combination.

[0040] The impact of fungi on the agricultural sector is also significant. Fungi are microorganisms that cause the largest number of plant diseases and food spoilage. They are linked to crop damage or reduced shelf life of foods. Fungi such as Penicillium expansum, Botrytis cinerea, Colletotrichum musae, Colletotrichum lindemuthianum, Stemphyllium spp., Rhizoctonia solani, Fusarium oxysporum fsp., Verticillium dahliae, Alternaria solani, Sclerotium rolfsii, Phytophthora infestans, and Septoria lycopersici are some of the fungi responsible for this negative impact.

[0041] Postbloom fruit drop (PFD), also known as citrus flower rot, is a disease caused by a fungus in the Colletotrichum family. It is one of the most important fungal diseases affecting citrus crops in the Americas due to the enormous damage it causes. Production in sweet orange groves can be reduced by up to 80% due to premature fruit or flower drop.

[0042] Asian soybean rust, caused by the fungus Phakopsora pachyhizi, is considered one of the most severe diseases affecting the crop. The cost of controlling the disease in Brazil is estimated at an average of US$2.8 billion per harvest, and when contamination occurs, producers can lose up to 90% of their crops.

[0043] Cyclodextrins (CDs) are widely used in various matrices due to their high commercial availability, relatively low acquisition cost, low toxicity, and known use in formulation of inclusion compounds and for their use as excipients in drug delivery vehicles and antiplatelet agents.

[0044] For many years, cyclodextrins were limited to excipients. However, more recent research has shown that these oligosaccharides can no longer be considered solely excipients in formulations. By serendipity, it was discovered that the use of hydroxypropyl-betacyclodextrin helps reduce the progression of Niemann-Pick disease type C. Based on studies that showed similar results, cyclodextrins were recently classified as active ingredients by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

[0045] Cyclodextrins are used to encapsulate compounds.

[0046] Generally, the inclusion compound is formed by weak interactions in the cyclodextrin's internal cavity, making the guest-host, i.e., compound-cyclodextrin, interaction reversible. Due to their toroidal structure, the hydrophobic cavity of cyclodextrins, and their more hydrophilic external surface, a favorable interaction occurs between the compound to be encapsulated and the cyclodextrin cavity.

[0047] Chlorhexidine is a broad-spectrum antimicrobial agent. However, its main action is antibacterial and directed against Gram-positive bacteria, with good action also against Gram-negative bacteria, yeasts and viruses. The mechanism of action of this active ingredient against bacteria has already been reported in the state of the art (Silva, DAR; Costa, MM; Vargas, AC; Alievi, MM; Schossler, JEW; Silva, TR Chlorhexidine gluconate or alcohol-iodine-alcohol in the antisepsis of surgical area in dogs, Ciência Rural, Santa Maria, 30 (3), 2000, p. 431-437).

[0048] Regarding its toxic activity in eukaryotic cells, chlorhexidine exhibits different levels of toxicity depending on the cell type affected. Epidermal, endothelial, mucosal, and osteoblast cells are most susceptible to this effect, while it has little effect on cell proliferation. In osteoblast cultures, exposure to 0.12% chlorhexidine caused lysis in 80% of the cells, including DNA fragmentation damage (Gendron et al., 1999; Gianelli et al., 2008).

[0049] Obtaining an antimicrobial agent that acts against biofilms and resistant microorganisms, is less toxic, has a fast action, and presents fewer side effects, or its combination with another active ingredient that optimizes its action, becomes strategic for the study and development of the pharmaceutical area, both human and veterinary.

[0050] The need to use active ingredients that can degrade the protection formed in the biofilm, which provides greater resistance to the structure, is still lacking in the literature with active ingredients with broad, effective, fast and low-toxicity action, or that do not cause damage to the material on which the biofilm is found.

[0051] In the prior art, there are some disclosures that present the use of antiseptic active ingredients against bacterial and fungal biofilms. Patent application WO2021174284, "Combination treatment for microorganisms," presents the combination of antiseptics such as chlorhexidine, alcohols, peroxides, and other organic groups within a method for use in the treatment of bacterial and fungal infections, as well as the treatment of biofilm formation. The patent also describes the use of transition metal cations within inorganic complexes in the formulation for combined action against microorganisms. This combination can create complexity in product stabilization and a risk of loss of activity over time. This application highlights the fact that there is activity against the most resistant structures without the need for a combination of active ingredients, and the mechanism of action differs from that already known for the active ingredient in its free state.

[0052] Prior art. WO2022041352, "Feed additive for preventing diarrhea and improving immunity, and preparation method therefor and application thereof," discloses an application in animal feed of cyclodextrin as a feed additive for preventing diarrhea and improving immunity, a preparation method and an application thereof. The feed additive is prepared by uniformly mixing compound amino acids, probiotic powder, nicotinamide, chitosan, P-cyclodextrin and fulvic acid; the preparation is used for adding to animal feed, especially for feeding poultry and livestock.

[0053] Document WO2017074285, "Antimicrobial surface coating material," also addresses the application of chlorhexidine against fungi, which describes the application of chlorhexidine to composite polymeric surfaces that have antimicrobial and antiviral properties. The invention presents polymeric composites containing additives, in which combinations of boron and / or zinc pyrithione compounds made with chlorhexidine gluconate and / or triclosan are used. The invention prevents biodegradation or biocontamination on surfaces. The technology claimed for protection aims to control pathogenic factors (bacteria, yeasts, fungi, and viruses), which are the causes of surface hygiene, allergies, and infectious diseases, in sectors (particularly agriculture, healthcare, food, and defense) where polymeric composites are widely used.

[0054] Document W02021205075A1 reports the use of macrocyclic structures in combination with antibiotics and their systemic use, which aims to sensitize bacteria, reducing the amount of active ingredient required for elimination, while inhibiting, treating, and preventing the formation of biofilms of pathogenic bacteria for human use. The study conducted in this prior art is the macrocyclic structure in an inclusion compound with pilararene, which acts to attenuate bacterial virulence by attaching a positively charged functional group to interact with liposaccharide structures. present in the membrane. They further state that, according to the present invention, the macrocyclic structure enables the use of previously used antimicrobial agents because it makes the bacteria susceptible to them again. They cite the fact that the presence of the structure hinders the formation of biofilms and state that such a structure, due to its size, cannot penetrate the bacteria, which is an advantage, since it would not contribute to microbial resistance.

[0055] Document US2018325117, entitled "Probiotic compositions and uses thereof," describes compositions useful in removing, reducing, eliminating, or preventing the presence of biofilm on any surface. Also included are methods of using the compositions to remove, reduce, eliminate, or prevent the presence of biofilm on any surface using in their formulation chlorine, chlorine dioxide, alcohol, hydrogen peroxide, sodium hypochlorite, an oxidant, quaternary ammonium, chlorhexidine, glutaraldehyde, a phenol, pine oil, or a derivative of any of the foregoing. The combination of active ingredients is a practice that has been widely used in the market, since the active ingredients, in their isolated form, in lower concentrations, can contribute to the formation of resistant microorganisms or biofilms, and in high concentrations they become toxic to cells.

[0056] Chlorhexidine as an antifungal active ingredient is difficult to use due to its low antibiofilm and antifungal activity against resistant fungi and the availability of better-cost-effective drugs on the market. However, its study and application in different matrices and systems is widespread, primarily due to its low toxicity and good stability in neutral to slightly acidic pH media.

[0057] These facts are described in order to illustrate the technical problem solved by the achievements of this document. GENERAL DESCRIPTION

[0058] The present invention consists of the uses of a composition comprising an inclusion compound (also called an inclusion complex) as a modulator of the activity of antiseptic active ingredients, causing a synergistic antimicrobial effect. More specifically, the present invention demonstrates the ability of cyclic oligosaccharides, namely cyclodextrins, to alter or modulate the spectrum of antimicrobial activity of an antiseptic active ingredient, enabling efficacy against microorganisms for which the active ingredient is ineffective in its isolated form or increasing its efficacy against fungi, resistant microorganisms, resistant fungi, and biofilms of microorganisms. The present invention also presents the novelty of the composition eliminating or hindering the development of resistant microorganisms, thanks to the specific characteristic of the cyclic oligosaccharide and its slow and continuous release. For resistant microorganisms that form biofilms, The prolonged antiseptic action obtained has a significant impact on combating the complex defenses created by the biofilm.

[0059] The composition indicated in the present invention is capable of preventing or eliminating biofilms, associating the physical-chemical characteristics of the cyclic oligosaccharide, its nanometric size, its capacity to form inclusion compounds with a wide variety of antimicrobial and / or antibiotic active ingredients and its interaction with the same compounds through weak and temporary bonds provides greater effectiveness, in addition to the release occurring gradually and continuously.

[0060] The present disclosure relates to a new mechanism of action, which uses known antiseptic active ingredients, in a compound, or inclusion complex, to achieve effectiveness in the elimination of microorganisms, namely fungi and fungal biofilms.

[0061] In the present disclosure, the inclusion compound is formed by weak interactions between the active ingredient (guest) and the internal cavity of the host, the cyclic oligosaccharide, making the guest-host interaction reversible. The formation of inclusion compounds results from the weak bonds between the free guest and the cyclic oligosaccharide, related by the formation (Kf) and stability (Ka) constants in an aqueous medium. Because these bonds are weak in the inclusion compounds, the strategy of encapsulating the guest initially and releasing the guest only later creates a sequence of activities fundamental to the effectiveness of the present invention.

[0062] The properties of cyclodextrins are fully utilized in the present invention. Due to their toroidal structure, hydrophobic cavity, and more hydrophilic outer surface, a favorable interaction occurs between the active ingredient to be encapsulated and the cyclodextrin cavity. The present invention uses active ingredients whose interaction occurs between the active ingredient and the cyclodextrin cavity, but this interaction is less stable compared to the interaction that occurs naturally between the microorganism's structure and the cyclodextrin cavity, allowing for the controlled release of the active ingredient into the biofilm.

[0063] Among the possible active ingredients used as antiseptics that can be combined with cyclodextrin (CHX) may be chlorhexidine and its various salts.

[0064] The present invention relates to the use of compositions utilizing an inclusion compound comprising at least one cyclic oligosaccharide and at least one antiseptic active ingredient for the elimination of resistant microorganisms, including fungi and biofilms of resistant microorganisms, and the application of the inclusion compound in various formulations and / or matrices. More specifically, the present invention relates to the use of compositions with highly efficient activity against biofilms of fungi, spores, viruses, mycobacteria, bacteria and polymicrobial biofilms of resistant fungi and resistant bacteria, having as main agents the cyclic oligosaccharide, the cyclodextrins, which act as activity-modulating agents in combined action with inclusion compounds formed by the same cyclic oligosaccharide and one or more antiseptic active ingredients, presenting an increase in spectrum and a highly efficient synergistic effect for the elimination of resistant or non-resistant microorganisms, even in biofilms, using a low concentration of the antiseptic active ingredient, quickly and safely for human, veterinary and agricultural use.

[0065] With the formation of the inclusion compound as proposed in the present invention, it is possible to significantly reduce the concentration of the antiseptic active ingredient, reducing the toxicity of the compositions and expanding the application of the active ingredient.

[0066] The present invention, which is claimed for protection, hinders the formation of resistant microorganisms, even with a single antimicrobial active ingredient present in the solution, thanks to its specific characteristic, combined with the residual action of the nanocompound, which enables a significant reduction in concentration and consequent reduction in toxicity.

[0067] The technology for which protection is sought uses betacyclodextrin as a cyclic structure. Its size is 7.8 Angstroms, which is within the nanoscale and smaller than the size of bacteria, allowing it to penetrate the cell wall and enabling the new mechanism of action. The spectrum of activity is another distinguishing feature of the present invention, since the compound formed, independent of the antiseptic active ingredient used, allows for the creation of activity previously absent from the free antiseptic active ingredient, including activity against fungi and biofilms. Another distinguishing feature of the present invention is the broad applicability of the inclusion composition, including addition to material bases and compositions intended for veterinary, agricultural, and sanitizing use, in addition to therapeutic applications for humans and veterinary use, both systemic and otherwise.

[0068] The physical characteristics of cyclodextrin in terms of size are an advantage, which, combined with the fact that it is a sugar, creates a favorable environment that facilitates the access of the active ingredient to more fragile regions of the microorganism, increasing the effectiveness of compounds formed by this structure and antimicrobial actives.

[0069] In one embodiment, among the possible active ingredients used as antiseptics that can be combined with cyclodextrin, there may be chlorhexidine and its various salts.

[0070] In the present invention, cyclodextrin is used in the formation of an inclusion compound with antimicrobial active ingredients to act in the prevention of infections caused by fungi present in animal feed.

[0071] The technology that is claimed for protection aims to control pathogenic factors (bacteria, yeasts, fungi and viruses), which are the causes of surface contamination, allergies and infectious diseases, with its application being particularly relevant in sectors such as agriculture, health, food and defense where polymer composites are widely used.

[0072] In one embodiment of the present invention, the macrocyclic structure in the inclusion compound formed with pilararene is sized to allow entry through the microorganism's cell wall. The inclusion composition of the present disclosure comprises a macrocyclic structure that is sized to penetrate the microorganism's cell wall, which, surprisingly, provides a complementary action to the antiseptic active ingredients used, increasing the effectiveness of the antimicrobial action, particularly the antibiofilm and antifungal action.

[0073] Surprisingly, the composition of the present disclosure enables the modulation of the activity of compounds with low fungal activity, fungal sporicidal or activity against fungal or mixed biofilm.

[0074] One aspect of the present disclosure relates to the use of an antimicrobial composition characterized by being used as an anti-fouling agent (from the English, anti-biofouling; that is, the use as an agent inhibiting the formation of biofilms and / or eliminating biofilms) and / or an agent enhancing the antimicrobial action against resistant microorganisms, fungi, bacteria, fungal biofilms, or algae; in which the composition comprises at least one cyclic oligosaccharide as an encapsulating agent, at least one antiseptic active ingredient; in which the encapsulating agent and the active ingredient form an inclusion compound (or complex).

[0075] In one embodiment, the molar ratio between the antiseptic active ingredient and the encapsulating agent may range from 8:1 to 1:10.

[0076] In another embodiment, the composition of the present disclosure may present a molar ratio between the antiseptic active ingredient and encapsulating agent that varies from 1:1 to 1:8; preferably from 1:2 to 1:4.

[0077] In another embodiment, the composition of the present disclosure may further comprise a free cyclic oligosaccharide.

[0078] In one embodiment, the mass of free cyclic oligosaccharide, relative to the total mass of the composition, may vary between 0.01% (m o free cyclic oligosaccharide / composition) 3 20.00% (free cyclic oligosaccharide / composition); preferably 5% (m o iigo ssafree cyclic oligosaccharide / composition) 3 15% (free cyclic oligosaccharide / composition) - That is, in some compositions there is an excess of the encapsulating agent (cyclic oligosaccharide) so the encapsulating agent can be found free in the composition, which allows the modulation of the activity of antimicrobial active ingredients to eliminate fungi, biofilms of resistant microorganisms allowing a synergistic effect in the composition.

[0079] In another embodiment, the composition of the present disclosure may comprise encapsulating agents selected from a list consisting of: betacyclodextrin, alphacyclodextrin, or gammacyclodextrin and / or their structural variations or mixtures thereof. These encapsulating agents act when combined with at least one antiseptic active ingredient as an active inclusion compound, this is an active complex, improving the effectiveness of the antimicrobial action and allowing the composition to be used as an antiscaling agent.

[0080] In one embodiment, the concentration of the antiseptic active ingredient may range from 0.005% to 30% (m / v); preferably 0.01% to 10% (m / v).

[0081] In one embodiment, the antiseptic active ingredient may be cationic, anionic, zwitterionic, or neutral; and / or selected from a list consisting of classes of: fa / s-biguanide, antimicrobial agent, essential oil, hydrolate, or mixtures thereof; preferably wherein the antimicrobial agent is an antibiotic, antifungal agent, antiparasitic agent, or mixtures thereof.

[0082] In one embodiment, the β / s-biguanide can be selected from a list consisting of: chlorhexidine, or its acetate, gluconate, or digluconate salts, or mixtures thereof.

[0083] In one embodiment, the antibiotic may be selected from a list consisting of: tetracycline, beta-lactam; aminoglycoside; macrolide; fluoroquinolone; sulfonamide; oxazolidinone; glycopeptide; streptogramin; rifamycins; or mixtures thereof.

[0084] In one embodiment, the antifungal agent may be selected from a list consisting of: azoles, polyenes, echinocandins, or mixtures thereof.

[0085] In one embodiment, the essential oil may be selected from a list consisting of: essential oil from natural bases such as thyme, eucalyptus, oregano, basil, mint, peppermint, levantia, horsetail, spearmint, rosemary, rosemary, pequi, geranium, citronella, palmarosa, pitanga, hibiscus, cypress, tea tree, ginger, lemongrass, ora-pro-nobis, moringa, cinnamon, muira puama, amapá, lemongrass or propolis, or mixtures thereof.

[0086] In one embodiment, the concentration of the essential oil may vary between 0.05% to 99.00% (w / w).

[0087] In one embodiment, the composition of the present disclosure may further comprise the addition of an organic acid and / or a saturated or unsaturated chain alcohol; preferably wherein the backbone of the organic acid and / or the saturated or unsaturated chain alcohol has a number of carbon atoms between 1 to 10; more preferably between 2 to 8.

[0088] In one embodiment, the composition of the present disclosure may further comprise at least one of the following excipients: humectant, emulsifier, preservative, thickener, sweetener, stabilizer, colorant, antioxidant, surfactant, drug delivery vehicle, or flavorings, or mixtures thereof; preferably polysorbate 20 as the emulsifier.

[0089] In one embodiment, the excipient concentration ranges from 0.02% to 99.00% (w / w); preferably 0.5% to 10% (w / w).

[0090] In one embodiment, the composition of the present disclosure may have antimicrobial activity against microorganisms selected from a list consisting of: Clostridioides difficile, Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Proteus mirabilis, Campylobacter spp., Salmonella spp., Klebsiella spp., Pseudomonas spp., Legionella spp., Acinetobacter spp., Enterococcus spp., Enterobacter spp., Aspergillus fumigatus, Candida spp. (Candida albicans, Candida auris, Candida tropicalis, or Candida parapsilose) Cryptococcus neoformans, Talaromyces marneffei, Pneumocystis jirovecii, Paracoccidioides brasiliensis, Histoplasma spp., Madurella spp., Nocardia spp. (associated with Eumycetoma), Nakaseomyces spp., Scedosporium apiospermum, Pseudallescheria spp., Lomentospora prolificans, Pichia kudriavzeveii, Cryptococcus gattii, Phakopsora pachyrizi (Asian soybean rust), Cercospora zeae-maydis, Microsporum spp., Trichophyton spp., Penicillium spp., Coccidioides spp., Epidermophyton spp., Malassezia spp., dermatophytes (such as Microsporum or Trichophyton), fungi of the order Mucorales, coronaviruses, or protozoa (Coccidia) alone or associated with other classes of microorganisms, even bacteria, mycobacteria, or algae.

[0091] In another embodiment, the composition of the present disclosure may have antiseptic antimicrobial activity against Candida auris.

[0092] In one embodiment, the composition of the present disclosure may be for pharmacological application either for systemic use or for local administration.

[0093] In one embodiment, the composition of the present disclosure may be for human or veterinary use on epithelial tissues, skin, mouth, fingers, eyes, nose, ears, nails, hair, mammary glands, perineal region, genitalia, mucous membranes, or wounds.

[0094] In one embodiment, the composition of the present disclosure may be for preparing a medicament for treating hair diseases, preferably for treating dandruff, hair dermatitis, primary cicatricial alopecia, or alopecia Tinea capitis and others.

[0095] In another embodiment, the composition of the present disclosure may be for preparing a medicament to treat candidiasis, preferably fungi of the Sacharomycetaceae family, in particular fungi of the Candida albicans and Candida auris species alone or associated with other types of microorganisms, such as bacteria and / or mycobacteria (resistant or not) in biofilms.

[0096] In another embodiment, the composition of the present disclosure may be for preparing a medicament for treating candidiasis, preferably candidiasis due to Candida auris infection.

[0097] In another embodiment, the composition of the present disclosure may be for preparing a medicament for treating cutaneous and subcutaneous mycoses caused especially by the fungi of genus Sporothríx, Trichophyton, Trichosporon, Epidermophyton, Microsporum, Fusarium, Fonsecaea, Cladosporium, Exophiala, or Malassezia.

[0098] In another embodiment, the composition of the present disclosure may be for preparing a medicament for treating bovine mastitis caused by the fungi Non-Aureus Staphylococcus, Staphylococcus epidermidis, or biofilms.

[0099] In another embodiment, the composition of the present disclosure may be for preparing a medicament for treating bovine mastitis caused by the fungi Staphylococcus aureus, Staphylococcus epidermis, Streptococcus dysgalactiae, Streptococcus agalactiae, Streptococcus uberis, Streptococcus bovis, Klebsiella pneumonia, or biofilms.

[0100] In another embodiment, the composition of the present disclosure may be for preparing an antiseptic used in foot bath solutions.

[0101] In another embodiment, the composition of the present disclosure may be for agricultural application; preferably as an agricultural pesticide for crops.

[0102] In one embodiment, said composition may be applied directly to seeds, soil, trunks, leaves and / or fruits.

[0103] In another embodiment, said composition may be for use in plantations as an agricultural defensive against fungi; preferably Penicillium, Botrytis, Colletotrichum, Colletotrichum, or Phakopsora pachyhizi; more preferably Penicillium expansum, Colletotrichum musae, or Colletotrichum lindemuthianum.

[0104] In another embodiment, said composition may be for use in plantations, as an agricultural defensive against fungi; preferably Penicillium, or Colletotrichum; more preferably Penicillium expansum, Colletotrichum musae, or Colletotrichum lindemuthianum.

[0105] In another embodiment, said composition can be applied as an agricultural pesticide against Asian soybean rust.

[0106] In another embodiment, said composition can be applied as an agricultural defensive against post-bloom fruit drop (PFD); preferably against a disease caused by a fungus of the Colletotrichum family; preferably a disease caused by the fungus Colletotrichum musae, or Colletotrichum lindemuthianum.

[0107] In one embodiment, said composition may be for use in foods for human or animal nutrition, and / or packaging to preserve and / or increase the shelf life of foods; preferably the foods are selected from a list of: animal protein, fruits, leaves, vegetables, minimally processed foods, processed cuisine, processed foods, or ultra-processed foods.

[0108] In another embodiment, the composition of the present disclosure may be for use as a sanitizer for disinfecting and / or sanitizing surfaces; and / or for producing formulations for treating environments, sanitizing and decontaminating hospital equipment, medical devices, water treatment systems and their structures, air purification systems, or any other critical level sanitization application.

[0109] In one embodiment, the composition of the present disclosure may be for application in plastic polymeric bases (acrylic resin), in organic and / or non-organic matrices, woven and / or non-woven matrices of synthetic, artificial, natural, or mixed composition; preferably cellulosic material (such as cellulosic resin) and / or cotton.

[0110] In one embodiment, said composition may further comprise an organic matrix; preferably cellulosic material; more preferably cellulosic resin.

[0111] In one embodiment, the composition of the present disclosure may be for application to woven and / or nonwoven matrices of synthetic, artificial, natural, or mixed composition.

[0112] In one embodiment, said composition may be in the form of an emulsion, aqueous solution, powder, paste, wet gel, lubricating oil, xerogels, aerosols, spray, foam, tablets, or capsules; preferably an emulsion.

[0113] Another aspect of the present disclosure relates to a composition characterized by comprising at least one cyclic oligosaccharide as an encapsulating agent, at least one antiseptic active ingredient; in which the encapsulating agent and the active ingredient form an inclusion compound (or complex), in which the composition is used for the treatment of diseases caused by biofilm in an individual or animal.

[0114] In one embodiment, the biofilm disease may be selected from a list of: recurrent urinary tract infections (associated with catheters), lung infections (in patients with cystic fibrosis, such as infections caused by Pseudomonas aeruginosa), periodontitis (biofilms in the oral cavity), gingivitis (biofilms in the oral cavity), chronic wounds (such as diabetic ulcers), infective endocarditis (when biofilms form on heart valves), infections associated with medical devices (such as orthopedic prostheses, pacemakers, and venous catheters).

[0115] In another embodiment, biofilm disease may be caused by a Candida auris biofilm.

[0116] In another embodiment, the composition of the present disclosure may comprise at least one cyclic oligosaccharide as an encapsulating agent, at least one antiseptic active ingredient; wherein the encapsulating agent and the active ingredient form an inclusion compound (or complex), wherein the composition is used as a coating on a medical device for use in the preventive treatment of biofilm-mediated medical device-associated infections in a subject.

[0117] In one embodiment, the medical device-associated infection is caused by Candida auris; preferably, said medical device-associated infection is a catheter-associated infection.

[0118] In one embodiment, the molar ratio between the antiseptic active ingredient and the encapsulating agent may range from 8:1 to 1:10.

[0119] In another embodiment, the composition of the present disclosure may present a molar ratio between the antiseptic active ingredient and encapsulating agent that varies from 1:1 to 1:8; preferably from 1:2 to 1:4.

[0120] In one embodiment, the composition of the present disclosure may further comprise a free cyclic oligosaccharide.

[0121] In one embodiment, the mass of free cyclic oligosaccharide, relative to the total mass of the That is, in some compositions there is an excess of the encapsulating agent (cyclic oligosaccharide) so the encapsulating agent can be found free in the composition, which allows the modulation of the activity of antimicrobial active ingredients to eliminate fungi, biofilms of resistant microorganisms, allowing a synergistic effect in the composition.

[0122] In one embodiment, the composition of the present disclosure may comprise encapsulating agents selected from a list consisting of: betacyclodextrin, alphacyclodextrin, or gammacyclodextrin and / or their structural variations or mixtures thereof. These encapsulating agents act when combined with at least one antiseptic active ingredient as an active inclusion compound, i.e., an active complex, improving the efficacy of the antimicrobial action and allowing the composition to be used as an antifouling agent.

[0123] In one embodiment, the concentration of the antiseptic active ingredient ranges from 0.005% to 30% (m / v); preferably 0.01% - 10% (m / v).

[0124] In one embodiment, the antiseptic active ingredient is cationic, anionic, zwitterionic, or neutral; and / or selected from a list consisting of classes of: b / s-biguanide, antimicrobial agent, essential oil, hydrolate, or mixtures thereof; preferably wherein the antimicrobial agent is an antibiotic, antifungal agent, antiparasitic agent, or mixtures thereof.

[0125] In one embodiment, ab / s-biguanide can be selected from a list consisting of: chlorhexidine, or its acetate, gluconate, or digluconate salts, or mixtures thereof.

[0126] In one embodiment, the antibiotic may be selected from a list consisting of: tetracycline, beta-lactam; aminoglycoside; macrolide; fluoroquinolone; sulfonamide; oxazolidinone; glycopeptide; streptogramin; rifamycins; or mixtures thereof.

[0127] In one embodiment, the antifungal agent may be selected from a list consisting of: azoles, polyenes, echinocandins, or mixtures thereof.

[0128] In one embodiment, the essential oil may be selected from a list consisting of: essential oil from natural bases such as thyme, eucalyptus, oregano, basil, mint, peppermint, levantia, horsetail, spearmint, rosemary, rosemary, pequi, geranium, citronella, palmarosa, pitanga, hibiscus, cypress, tea tree, ginger, lemongrass, ora-pro-nobis, moringa, cinnamon, muira puama, amapá, lemongrass or propolis, or mixtures thereof.

[0129] In one embodiment, the concentration of the essential oil may range from 0.05% to 99.00% (w / w).

[0130] In one embodiment, the composition of the present disclosure may further comprise the addition of an organic acid and / or a saturated or unsaturated chain alcohol; preferably wherein the backbone of the organic acid and / or the saturated or unsaturated chain alcohol has a number of carbon atoms between 1 to 10; more preferably between 2 to 8.

[0131] In one embodiment, the composition of the present disclosure may further comprise at least one of the following excipients: humectant, emulsifier, preservative, thickener, sweetener, stabilizer, colorant, antioxidant, surfactant, drug delivery vehicle, or flavorings, or mixtures thereof; preferably polysorbate 20 as the emulsifier.

[0132] In one embodiment, the excipient concentration may range from 0.02% to 99.00% (w / w); preferably 0.5% to 10% (w / w).

[0133] In one embodiment, said composition may further comprise an organic matrix; preferably cellulosic material; more preferably cellulosic resin.

[0134] In one embodiment, said composition may be in the form of an emulsion, aqueous solution, powder, paste, wet gel, lubricating oil, xerogels, aerosols, spray, foam, tablets, or capsules; preferably an emulsion.

[0135] In one embodiment, the disease is a medical device-associated infection and is caused by Candida auris; preferably, said medical device-associated infection is a catheter-associated infection.

[0136] Another aspect of the present disclosure relates to a coated surface or coated article, wherein the coating is on a medical device and comprises the composition described in this disclosure, for use in the preventative treatment of biofilm-mediated medical device-associated infections in an individual.

[0137] In one embodiment, the coated surface or article may additionally comprise at least 0.01% (w / v) of the composition described in this disclosure.

[0138] In another embodiment, the coated surface or article may be a medical device, preferably selected from the list consisting of a catheter, a syringe, a stent, a tube, a medical package, a dialysis device, a dental prosthesis, a dental implant, an orthodontic device, a mask, or clothing. BRIEF DESCRIPTION OF THE FIGURES

[0139] For easier understanding, the figures are attached, which represent preferred embodiments that are not intended to limit the scope of this description. Figure 1. Illustration of the results, in millimeters, of the average readings of the halos obtained in each of the samples, in relation to the tested microorganism Penicillium expansum, being in a) sample A6, b) sample A2 and in c) sample A7. DETAILED DESCRIPTION

[0140] The present invention relates to the use of cyclic oligosaccharides as modulators of the activity of antiseptic active ingredients, creating a synergistic effect in antimicrobial compositions. More specifically, the present invention demonstrates the ability of cyclic oligosaccharides to alter or modulate the spectrum of antimicrobial activity of an antiseptic active ingredient, enabling efficacy against microorganisms for which the active ingredient is ineffective in isolation or increasing its efficacy against fungi, resistant microorganisms, such as resistant fungi, and biofilms of microorganisms. The present invention also features the novelty of the composition hindering the development of resistant microorganisms and / or eliminating resistant microorganisms, thanks to the specific characteristic of the cyclic oligosaccharide and the slow and continuous release of the antiseptic active ingredient.For biofilms of resistant microorganisms, the prolonged antiseptic action obtained has a significant impact in combating the complex defenses created by biofilms.

[0141] The present invention presents as a novelty the positive modulation of the activity of antiseptic active ingredients, which do not present, in their isolated form, satisfactory antifungal, fungal sporicidal and / or antibiofilm activity and which, after encapsulation with betacyclodextrin in varied molar concentrations, become antifungal, antibiofilm and fungal sporicidal active ingredients with application in low concentration and safe for human, veterinary and agricultural use.

[0142] Chlorhexidine and its salts are not significantly active against resistant fungi, fungal spores, and biofilms. In one embodiment, the combination of chlorhexidine or its salts with betacyclodextrin, in varying molar concentrations, to obtain inclusion compounds, showed modulation of chlorhexidine activity, allowing application in low concentrations in systems now sensitive to chlorhexidine, enabling application in safe concentrations for use.

[0143] The modulation of activity that occurs in the present invention is related to the fact that the compound / inclusion complex formed by the antiseptic active ingredient with the cyclic oligosaccharide has activity against fungal biofilms, resistant fungi, bacterial biofilms and resistant bacteria or polymicrobial biofilms, even when the antiseptic active ingredient does not present activity in its free form, even in high concentrations.

[0144] The characteristics of cyclodextrins, as a nano-sized cyclic oligosaccharide, differentiate them from other larger macrocyclic structures; their nanostructure allows physical permeation and positively contributes to their use as an activity modulator in antiseptic compositions. Dextrins, like sugars, are able to permeate the structures of microorganisms, easily accessing their interiors, as they are mistaken for food by microorganisms. Another distinguishing feature is their ability to form inclusion compounds with different active ingredients or functional groups of antiseptic actives, hiding them, thus altering the method of reading used by microorganisms, including those that have already been able to create special defense mechanisms, such as biofilms or resistant microorganisms.

[0145] The resistance of microorganisms is related to their ability to survive the antiseptic or antibiotic active ingredients commonly used to combat them, and one of the triggers is the "closure" of all oxygen and food receiving channels, when there is the presence of any antiseptic functional group that can be recognized as a threat.

[0146] Thus, in the present disclosure, with nanoencapsulation, it was possible for the cyclodextrins to interact with the functional groups of the antiseptic active ingredients, in order to temporarily hide it. There is an inclusion compound and the bacteria are no longer able to read the presence of the antiseptic active ingredient; it will not close, allowing the penetration of the compounds into the most sensitive layers of the microorganisms.

[0147] In the present invention, considering the weak and temporary bonds that are created between the functional groups of the antiseptic active ingredient and the internal cavity of the cyclodextrin, there will be a subsequent release of this same active ingredient after the penetration of the inclusion compound, allowing, in low concentrations, effectiveness against the pathogenic agent.

[0148] This technology also highlights the differential antiseptic action, achieved through gradual release, enabling prolonged action. For structures such as biofilms, where the deeper layers are responsible for ensuring their survival, the differential residual action is crucial for satisfactory antibiofilm activity.

[0149] The resilience of cyclodextrins also contributes positively to the combination of different antiseptic active ingredients to develop inclusion compounds / compositions that enable a synergistic effect. Chlorhexidine is highlighted as an example of this active ingredient in the present invention; however, any antiseptic active ingredient that forms an inclusion compound with cyclodextrins can be used and constitute an option for the novelty of the invention.

[0150] In one embodiment, the option of adding free cyclodextrins contributes to the modulation of the activity and synergistic effect previously non-existent for the free antiseptic active ingredient, which is justified by the interaction that occurs between the cyclodextrin cavity and the structure of the microorganism, weakening its defenses and contributing to the action of the nanoencapsulated antiseptic active ingredient.

[0151] In definition, a synergistic effect occurs when drugs interact to enhance or magnify one or more of their effects, or even reduce their side effects. The fact that cyclodextrin was recently included in the list of active ingredients of the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) allows the inclusion compound of the present invention to no longer be viewed solely as an excipient. In this disclosure, attention is drawn to the novelty and inventive nature of this cyclic oligosaccharide, which exhibits activity against the structures of microorganisms, even though it is not effective in isolation, facilitating the action of the inclusion compound and the antiseptic active ingredient.

[0152] In this disclosure, there is the creation of activity for an active ingredient that, in isolation, does not present activity for certain resistant microorganisms or biofilms with different microorganisms combined.

[0153] In this disclosure, it was demonstrated that cyclodextrin actively interacts with the cellular structure of resistant or non-resistant microorganisms, potentially contributing to biofilm formation and weakening the biofilm through mechanisms of action distinct from those known for the free antiseptic active ingredient. Its unique characteristic of weak and temporary bonds, which also provides prolonged action, is a determining factor in the novel mechanism of action proposed in this invention.

[0154] In one embodiment, the inclusion composition comprises free cyclic oligosaccharides, with the purpose of leaving the cyclic oligosaccharide (cyclodextrin) available for interaction with the cell wall of the microorganism and the inclusion compounds formed with the antiseptic active ingredients, creating a more effective antimicrobial environment of activity against resistant microorganisms and biofilms.

[0155] In one embodiment, the technology for which protection is sought presents as a novelty the use of an inclusion compound with cyclodextrins as modulating agents of the activity of antiseptic active ingredients, resulting in products that surprisingly present superior activity to the active ingredients applied individually against fungi, resistant fungi, fungal spores and fungal and bacterial biofilms and for human, veterinary and polymeric or organic matrix applications, even in low concentrations.

[0156] In one embodiment, the inclusion composition with antibiofilm and / or antifungal activity used presents encapsulating agents, free or not, being cyclic oligosaccharides, at least one antiseptic active in an inclusion compound with cyclic oligosaccharide and excipients or mixture thereof, being characterized by the modulation of activity of antimicrobial active ingredients for the elimination of fungi, fungal biofilms, algae or bacteria and resistant microorganisms.

[0157] In one embodiment, the encapsulating agents would be, in particular, betacyclodextrin and / or its structural variations, or a mixture thereof. Possible structural variations of betacyclodextrin include the compounds hydroxypropyl-betacyclodextrin, sodium betadexsulfobutylether, hydroxymethyl-betacyclodextrin, methyl-betacyclodextrin, 2,6-dimethyl-betacyclodextrin, and hydroxyethyl-betacyclodextrin.

[0158] In another embodiment, the antiseptic active ingredient must be a cationic, anionic, zwitterionic or neutral antimicrobial active ingredient, such as the bis-biguanide class, such as chlorhexidine or its acetate, gluconate, or digluconate salts, and the tetracycline classes, such as doxycycline, eracycline, monocycline, omadacycline, or a combination thereof.

[0159] In one embodiment, the antiseptic active ingredient may be comprised of the unitary addition or mixture of classes of organic acids or alcohols with a saturated or unsaturated chain, with a main chain having a number of carbon atoms between 2 and 8, or a combination thereof, in a concentration between 0.01% and 30.00% (m / v).

[0160] In another embodiment, the antiseptic may also belong to the group of essential oils or hydrolates of essential oils provided with natural bases such as thyme, eucalyptus, oregano, basil, mint, peppermint, levantia, horsetail, spearmint, rosemary, field rosemary, pequi, geranium, citronella, palmarosa, pitanga, hibiscus, cypress, tea tree, ginger, lemongrass, ora-pro-nóbis, moringa, cinnamon, muira puama, amapá, lemongrass or propolis, or a combination of these in concentrations between 0.05% and 99.00% (w / w).

[0161] In one embodiment, the excipients of the inclusion composition may be selected from a list consisting of: humectants, emulsifiers, preservatives, thickeners, sweeteners, stabilizers, colorants, antioxidants, surfactants, flavorings, or a combination thereof in concentrations between 0.02% and 99% (w / w).

[0162] In one embodiment, the antiseptic active ingredient and the encapsulating agent must be in molar ratios between 8:1 and 1:10, respectively.

[0163] In another embodiment, the encapsulating agent, namely betacyclodextrin and / or its structural variations, or a combination thereof, must be in excess in the product in a range of 0.01% to 20% (w / w) in the final composition, being used as a modulator of the activity of antimicrobial active ingredients for the elimination of fungi, biofilms and resistant microorganisms.

[0164] One aspect of the present invention relates to the use of betacyclodextrin and / or its structural variations, or a combination thereof, as a modulator of antifungal and / or antibiofilm activity of active antiseptic agents against microorganisms selected from a list consisting of: Aspergillus fuminatus, Cryptococcus neoformans, Candida, Candida albicans, Candida auris, Histoplasma, Eumycetoma, Candida tropicalis, Nakaseomyces, Candida parapsilosis, Scedosporium apiospermum, Pseudallescheria spp, Lomentospora prolificans, Pichia kudriavzeveii, Cryptococcus gattii, Talaromyces marneffei, Pneumocystis jirovecii and Paracoccidioides brasiliensis, Phakopsora pachyrizi, Cercospora zeae-maydis, Escherichia coli, Staphylococcus aureus, Proteus mirabilis of the genera Microsporum, Sacharomycetaceae, Trichophyton, Coccidioides, Epidermophyton, Malassezia, Enterococcus, Klebsiella, Pseudomonas, Penicillium, Acinetobacter and Legionella, Enterobacter bacillus and the order Mucorales,alone or associated with other classes of microorganisms, even bacteria, mycobacteria or algae.,

[0165] One aspect of the present invention relates to the use of the inclusion composition with antibiofilm and / or antifungal activity for the production of a drug for pharmacological application for systemic use, such as an antibiotic in solid, liquid, semi-solid, injectable, and / or related forms.

[0166] One aspect of the present invention also relates to the use for topical treatment of tissues, selected from the group comprising: epithelial tissues, skin, mouth, fingers, nails, hair, mammary glands, perineal region, genitalia, or mucosa.

[0167] One aspect of the present invention relates to veterinary use in the topical dermatological treatment of animals.

[0168] One aspect of the present invention relates to the use and insertion in animal feed.

[0169] Another aspect of the present invention relates to the use in plastic polymeric packaging or in organic matrices, such as cellulose material or cotton.

[0170] Another aspect of the present invention relates to the use of the antimicrobial composition to prepare a medicine to treat hair diseases, such as dandruff, hair dermatitis, primary cicatricial alopecia, Tinea capitis alopecia, among others.

[0171] Another aspect of the present invention relates to the use of the antimicrobial composition to prepare a medicament to treat candidiasis, preferably fungi of the Sacharomycetaceae family, in particular fungi of the species Candida albicans and Candida auris alone or associated with other types of microorganisms, such as bacteria and mycobacteria.

[0172] Another aspect of the present invention relates to the use of the antimicrobial composition to prepare a medicament to treat cutaneous and subcutaneous mycoses caused especially by fungi of the genus Sporothrix, Trichophyton, Trichosporon, Epidermophyton, Microsporum, Fusarium, Fonsecaea, Cladosporium, Exophiala and Malassezia.

[0173] Another aspect of the present invention relates to the veterinary use of the antimicrobial composition that is used to prepare a medicine to treat bovine mastitis, caused by the fungi: Non-Aureus Staphylococcus, Staphylococcus epidermidis and their biofilms.

[0174] Another aspect of the present invention relates to the use of the composition of the present disclosure to prepare an antiseptic used in foot bath solutions.

[0175] Another aspect of the present invention relates to its use in agricultural applications, especially as an agricultural pesticide applied to plants or fruits, extending the shelf life of foods. In one embodiment, these applications may be for the topical or systemic treatment of diseases caused by fungi of the families Sacharomycetaceae and Malasseziaceae, especially the species Malassezia furfur, and the family Arthrodermataceae, especially the species Trichophyton, Microsporum, and Epidermophyton.

[0176] Another aspect of the present invention relates to the use of the antimicrobial composition as an agricultural defensive, especially against fungi: Penicillium, Botrytis, Colletotrichum, Colletotrichum, or Phakopsora pachyhizi.

[0177] Another aspect of the present invention relates to the use of the present invention to prepare an agricultural pesticide to treat Asian soybean rust. In one embodiment, the present invention is used specifically against postbloom fruit drop (PFD), also known as citrus leaf rot, a disease caused by a fungus of the Colletotrichum family.

[0178] Yet another aspect of the present invention relates to the use of the antimicrobial composition to be a sanitizer for surface disinfection and / or sanitization, for the production of formulations for topical use, or for environmental treatment, sanitization and decontamination of hospital equipment, medical devices, water treatment systems and their structures, air purification systems, or any other critical level sanitization application, sanitization of air conditioning systems, or in air purification equipment.

[0179] In one embodiment, the present invention may be applied in aqueous solution, powder, paste, wet gel, lubricating oil, xerogels, aerosols, spray, foam, tablets, capsules or in adhesives, whether or not inserted into cellulosic, polymeric materials or fabrics.

[0180] In another embodiment, the antimicrobial composition can be applied to plastic polymeric bases or to organic matrices such as cellulose material or cotton, or woven or non-woven matrices of synthetic, artificial, natural or mixed composition.

[0181] This technology can be better understood with the following non-limiting examples. Example 1. Initial processes for preparing inclusion compound compositions in different molar proportions.

[0182] In one embodiment, the process of preparing solutions with inclusion compounds was carried out by adding the compound to be encapsulated, such as chlorhexidine salt, to an aqueous solution containing beta-cyclodextrin encapsulant at 60°C, maintaining the molar proportions at 1:1 (A1), 1:2 (A2), 1:3 (A3) or 1:4 (A4), respectively, following the procedure reported in the literature with minor changes (CORTÉS et al., The chlorhexidine:6-cyclodextrin Inclusion compounds: preparation, characterization and microbial evaluation. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 40, 2001, 297-302). Table 1. Compositions of inclusion compounds / complexes in different molar ratios. Example 2. Processes for preparing emulsions of inclusion compounds in different molar proportions.

[0183] In one embodiment, the emulsion preparation process was carried out by adding the inclusion compound to distilled water, under constant stirring and at room temperature. Then, polysorbate 20 pre-diluted in distilled water was added in an equimolar proportion. The process Polysorbate 20 was inserted using high pressure and vigorous stirring. The emulsion (A5) was kept stirring for 10 minutes and then transferred to a container and set aside. Table 2. Composition of emulsion A5. Example 3. Processes for inserting the inclusion compound into a matrix for Cobb increase in paper.

[0184] In one embodiment, the process of inserting the inclusion compound into cellulose resin was carried out by adding 3.0g of inclusion compound A2, solubilized in 42.0g of distilled water, to 5.0g of acrylic resin (A6), forming a 10% resin solution (5g / 50g), or 3.0g of inclusion compound A2, 3.5g of starch, and 43.5g of distilled water (A7), forming a 7% starch suspension (3.5g / 50g). Both matrices (resin and starch) are used to increase the Cobb (a measure of a paper's water absorption capacity). The mixture was vigorously stirred for 20 minutes at room temperature. The mixtures were transferred to containers and set aside. Table 3. Composition A6. Example 4. Studies of antifungal activity using inhibition halo analysis against the fungus Penicillium expansum with application of the encapsulated product on a cellulose matrix.

[0185] In one study, each test microorganism was inoculated into Petri dishes containing Mueller Hinton +2% glucose culture medium. Using sterile scissors and a mold, the samples were marked and cut into 0.8 cm diameter discs. One disc was inoculated onto the surface of the Petri dishes with the inoculated fungal suspensions. The plates were incubated at 25°C. The test The test was performed in triplicate, all accompanied by positive controls (fungal suspension + culture medium) and negative controls (sample + culture medium). The results were read after 10 days of plate incubation, during which the presence or absence of a halo around the inoculated sample was verified. If an inhibition halo formed, its diameter was measured and the result expressed in millimeters.

[0186] In one test, the formation of a microbial growth inhibition halo was observed when the Penicillium expansum fungus was tested (Fig. 1). There was adequate development of the test microorganism on the control plates.

[0187] The methodologies used were: Standardization of Antimicrobial Susceptibility Tests - Anvisa / CLSI Method (M2-A8, Vol. 23 No. 1). Method for evaluating the inhibitory activity of preparations in liquid, creamy, and solid forms, Manual of Disinfectants, INCQS / FioCruz, 1992. Agar plate diffusion method. BLOCK, SS; Disinfection, Sterilization and Preservation, 4th ed. 1991. The analyses were performed in the laboratories of the Tropical Culture Collection, André Tosello Foundation. Table 4: Results, in millimeters, of the average halo readings obtained in each sample, compared to the microorganism tested. Results in Fig. 1. Example 6. Studies of antifungal activity against the fungus Candida auris.

[0188] In one study, antifungal activity tests were performed for active ingredient A2 against the fungus Candida auris (C. auris) using the minimum inhibitory concentration (MIC) methodology. The test used inclusion compound A2 in distilled water as the base solution, with an initial test concentration of 1.5%. The studies showed that the active ingredient had a MIC value of 0.0058% (w / w) against the microorganism. Example 7. Studies of antibiofilm activity of the fungus Candida auris.

[0189] In one embodiment, for biofilm formation, an inoculum of 10 7cells / mL in Sabouraud Dextrose (SD) Agar broth (200 pL) was incubated in 96-well polystyrene plates for 24 h at 37°C. The metabolic viability of the biofilm was assessed by the MTT reduction assay (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2 H-tetrazolium bromide, Sigma).

[0190] In one instance, all products tested were effective in inhibiting microbial biofilms, as shown in the tables below. Table 5. Resulting minimum inhibitory concentration.

[0191] In one embodiment, the final result concludes that both inclusion compounds A2 and A3 are effective in eliminating mature biofilm of the super fungus Candida auris. Example 8. Studies of inhibitory, antifungal activity of the fungus Colletotrichum musae and Colletotrichum lindemuthianum.

[0192] Determination of minimum inhibitory concentration performed according to USP Methodology XXIII, Antibiotics: Microbial Assays, US Pharmacopeia and Larpent, JP Practical Microbiology, Edgard Blücher, p. 80. Methodology of Antimicrobial Susceptibility Tests by Dilution for Aerobically Growing Bacteria: Approved Standard - Sixth Edition. National Committee for Clinical Laboratory Standards, 2003. The analysis was performed with samples TNEA21201 (A2) and B2H20I04 (A3) in concentrated powders (98-100%) where the first dilution tested was 50% dilution, from which biserial dilutions (50%) were performed. The test was performed in triplicate and the results are reported in Table 6. Table 6. Results obtained from the averages of the minimum inhibitory concentration analyses of the sample analyzed, against the selected microorganisms.

[0193] Where ranges are given, extremes are included. Furthermore, it is understood that, unless otherwise indicated or evident from the context and / or the knowledge of a person skilled in the art, values ​​expressed as ranges may assume any specific value within the stated limits, in different embodiments of the invention, with an accuracy of up to one-tenth of a unit. of the lower limit of the interval, unless the context clearly requires otherwise. It is also understood that, unless otherwise indicated or evidenced by the context and / or the knowledge of an expert in the field, values ​​expressed as intervals may encompass any subinterval within the given interval, provided that the extremes of that subinterval are expressed with the same precision (to within one-tenth of a unit of the lower limit of the original interval).

[0194] As used herein, the terms 'treatment' or 'treating' refer to a pharmaceutical regimen or other intervention designed to achieve beneficial or desired results in the recipient. Beneficial or desired results include, but are not limited to, a therapeutic and / or prophylactic benefit. A therapeutic benefit may refer to the eradication or attenuation of symptoms or the underlying condition being treated. Additionally, a therapeutic benefit may be achieved by eradicating or attenuating one or more physiological symptoms associated with the underlying condition, resulting in an improvement in the patient's condition, even if the patient continues to suffer from the underlying condition. As used herein, the term 'treatment' or 'treating' refers to the therapeutic intervention, management, or alleviation of a disease, disorder, or condition in a patient. Unless otherwise specified, the term encompasses both human and animal patients, hence its use in medicine and / or veterinary medicine.A prophylactic effect includes delaying, preventing, or eliminating the onset of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, stopping, or reversing the progression of a disease or condition, or any combination of these actions. For a prophylactic benefit, a patient at risk of developing a particular disease, or a patient exhibiting one or more physiological symptoms of a disease, may undergo treatment even if a formal diagnosis of the disease has not yet been established.

[0195] The term "comprises" or "comprising" when used in this document is intended to indicate the presence of the features, elements, integers, steps and components mentioned, but does not preclude the presence or addition of one or more other features, elements, integers, steps and components, or groups thereof.

[0196] The present invention is, of course, in no way restricted to the embodiments described in this document and a person with average knowledge of the area will be able to foresee many possibilities for modifying it and replacing technical characteristics with equivalent ones, depending on the requirements of each situation, as defined in the attached claims.

[0197] The following claims define additional embodiments of the present description.

Claims

CLAIMS 1. Use of an antimicrobial composition characterized by being used as an anti-fouling agent and / or agent enhancing antimicrobial action against resistant microorganisms, fungi, bacteria, fungal biofilms, or algae; in which the composition comprises at least one cyclic oligosaccharide as an encapsulating agent, at least one antiseptic active ingredient; in which the encapsulating agent and the active ingredient form an inclusion compound.

2. Use of a composition according to the previous claim, characterized in that the molar ratio between the antiseptic active ingredient and the encapsulating agent varies between 8:1 and 1:

10.

3. Use of a composition, according to the previous claims, characterized by presenting a molar ratio between the antiseptic active ingredient and encapsulating agent that varies from 1:1 to 1:8; preferably from 1:2 to 1:

4.

4. Use of a composition according to any one of the preceding claims, characterized in that it further comprises a free cyclic oligosaccharide.

5. Use of a composition according to any one of the preceding claims, characterized in that the mass of free cyclic oligosaccharide, relative to the total mass of the composition, varies between 6. Use of a composition according to any one of the preceding claims, characterized in that it comprises encapsulating agents selected from a list consisting of: betacyclodextrin, alphacyclodextrin, or gammacyclodextrin and / or their structural variations or mixtures thereof.

7. Use of a composition according to any one of the preceding claims, characterized in that the concentration of the antiseptic active ingredient varies from 0.005% to 30% (m / v); preferably 0.01% - 10% (m / v).

8. Use of a composition according to any one of the preceding claims, characterized in that the antiseptic active ingredient is cationic, anionic, zwitterionic, or neutral; and / or selected from a list consisting of classes of: £> / s-biguanide, antimicrobial agent, essential oil, hydrolate, or mixtures thereof; preferably wherein the antimicrobial agent is an antibiotic, antifungal agent, antiparasitic agent, or mixtures thereof.

9. Use of a composition according to the preceding claim, characterized in that the b / s-biguanide is selected from a list consisting of: chlorhexidine, or its acetate, gluconate, or digluconate salts, or mixtures thereof.

10. Use of a composition according to claim 8, characterized in that the antibiotic is selected from a list consisting of: tetracycline, beta-lactam; aminoglycoside; macrolide; fluoroquinolone; sulfonamide; oxazolidinone; glycopeptide; streptogramin; rifamycins; or mixtures thereof.

11. Use of a composition according to claim 8, characterized in that the antifungal agent is selected from a list consisting of: azoles, polyenes, echinocandins, or mixtures thereof.

12. Use of a composition according to claim 8, characterized in that the essential oil is selected from a list consisting of: essential oil from natural bases such as thyme, eucalyptus, oregano, basil, mint, peppermint, levantia, horsetail, mint, rosemary, field rosemary, pequi, geranium, citronella, palmarosa, pitanga, hibiscus, cypress, tea tree, ginger, lemongrass, ora-pro-nóbis, moringa, cinnamon, muira puama, amapá, lemongrass or propolis, or mixtures thereof.

13. Use of a composition, according to the previous claim, characterized in that the concentration of the essential oil varies between 0.05% and 99.00% (m / m).

14. Use of a composition according to any one of the preceding claims, characterized in that the composition further comprises the addition of an organic acid and / or a saturated or unsaturated chain alcohol; preferably wherein the main chain of the organic acid and / or the saturated or unsaturated chain alcohol has a number of carbon atoms between 1 and 10; more preferably between 2 and 8.

15. Use of a composition according to any one of the preceding claims, characterized in that it further comprises at least one of the following excipients: humectant, emulsifier, preservative, thickener, sweetener, stabilizer, colorant, antioxidant, surfactant, drug delivery vehicle, or flavorings, or mixtures thereof.

16. Use of a composition according to the previous claim, characterized in that the excipient concentration varies between 0.02% to 99.00% (m / m); preferably 0.5% to 10% (m / m).

17. Use of a composition according to any one of the preceding claims, characterized in that it has antimicrobial activity against microorganisms selected from a list consisting of: Clostridioides difficile, Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Proteus mirabilis, Campylobacter spp., Salmonella spp., Klebsiella spp., Pseudomonas spp., Legionella spp., Acinetobacter spp., Enterococcus spp., Enterobacter spp., Aspergillus fumigatus, Candida spp., Cryptococcus neoformans, Talaromyces marneffei, Pneumocystis jirovecii, Paracoccidioides brasiliensis, Histoplasma spp., Madurella spp., Nocardia spp., Nakaseomyces spp., Scedosporium apiospermum, Pseudallescheria spp., Lomentospora prolificans, Pichia kudriavzeveii, Cryptococcus gattii, Phakopsora pachyrizi, Cercospora zeae-maydis, Microsporum spp., Trichophyton spp., Penicillium spp., Coccidioides spp., Epidermophyton spp., Malassezia spp., dermatophytes, fungi of the order Mucorales, coronaviruses, or protozoa alone or associated with other classes of microorganisms, even bacteria, mycobacteria or algae.

18. Use of a composition, according to the previous claim, characterized by having antiseptic antimicrobial activity against Candida auris.

19. Use of the composition, according to any of the preceding claims, characterized in that it is for pharmacological application, whether for systemic use or for local administration.

20. Use of the composition, according to the previous claim, characterized by being for human or veterinary use in epithelial tissues, skin, mouth, fingers, eyes, nose, ears, nails, hair, mammary glands, perineal region, genitalia, mucous membranes or wounds.

21. Use of composition, according to any one of the previous claims, characterized in that it is to prepare a medicament to treat hair diseases, preferably to treat dandruff, hair dermatitis, primary cicatricial alopecia, or alopecia Tinea capitis and others.

22. Use of composition according to any one of the preceding claims 1-16, characterized in that it is for preparing a medicament to treat candidiasis, preferably fungi of the Sacharomycetaceae family, in particular fungi of the species Candida albicans and Candida auris alone or associated with other types of microorganisms, such as bacteria and / or mycobacteria.

23. Use of composition, according to the previous claim, characterized in that it is to prepare a medicament to treat candidiasis, preferably candidiasis due to infection by Candida auris.

24. Use of composition according to any one of the preceding claims 1-16, characterized in that it is for preparing a medicament to treat cutaneous and subcutaneous mycoses caused especially by fungi of the genus Sporothrix, Trichophyton, Trichosporon, Epidermophyton, Microsporum, Fusarium, Fonsecaea, Cladosporium, Exophiala, or Malassezia.

25. Use of composition according to any one of the preceding claims 1-16, characterized in that it is to prepare a medicament to treat bovine mastitis caused by the fungi Staphylococcus aureus, Staphylococcus epidermis, Streptococcus dysgalactiae, Streptococcus agalactiae, Streptococcus uberis, Streptococcus bovis, Klebsiella pneumonia or biofilms.

26. Use of composition according to any one of the preceding claims 1-16, characterized in that it is for preparing an antiseptic used in foot bath solutions.

27. Use of composition, according to any one of the previous claims 1-16, characterized by being for agricultural application; preferably as an agricultural pesticide for plantations.

28. Use of composition, according to the previous claim, characterized in that said composition is applied directly to seeds, soil, trunks, leaves and / or fruits.

29. Use of composition according to any one of the preceding claims 27-28, characterized in that said composition is for use in plantations as an agricultural defensive against fungi; preferably Penicillium, Botrytis, Colletotrichum, Colletotrichum, or Phakopsora pachyhizi; more preferably Penicillium expansum, Colletotrichum musae, or Colletotrichum lindemuthianum.

30. Use of composition according to any one of the preceding claims 27-29, characterized in that said composition is applied as an agricultural defensive against post-flowering fruit drop; preferably against a disease caused by the fungus of the Colletotrichum family; preferably a disease caused by the fungus Colletotrichum musae, or Colletotrichum lindemuthianum.

31. Use of composition according to any one of the preceding claims 1-16, characterized in that said composition is for use in foods for human or animal nutrition, and / or packaging to preserve and / or increase the durability of foods; preferably the foods are selected from a list of: animal protein, fruits, leaves, vegetables, minimally processed foods, processed cuisine, processed foods, or ultra-processed foods.

32. Use of composition according to any one of the preceding claims 1-16, characterized in that it is for use as a sanitizer for disinfecting and / or sanitizing surfaces; and / or for producing formulations for treating environments, sanitizing and decontaminating hospital equipment, medical devices, water treatment systems and their structures, air purification systems, or any other critical level sanitization application.

33. Use of composition according to any one of the preceding claims 1-16, characterized in that it is for application on plastic polymeric bases, in organic and / or non-organic matrices, woven and / or non-woven matrices of synthetic, artificial, natural, or mixed composition; preferably cellulose material and / or cotton.

34. Use of composition according to any one of the preceding claims 1-33, characterized in that said composition is in the form of an emulsion, aqueous solution, powder, paste, wet gel, lubricating oil, xerogels, aerosols, spray, foam, tablets, or capsules; preferably an emulsion.

35. Composition characterized by comprising at least one cyclic oligosaccharide as an encapsulating agent, at least one antiseptic active ingredient; in which the encapsulating agent and the active ingredient form an inclusion compound, in which the composition is used for the treatment of diseases caused by biofilm in an individual or animal.

36. Composition, according to the previous claim, characterized in that the disease caused by biofilm is selected from a list of: recurrent urinary infections, lung infections (in patients with cystic fibrosis, such as infections caused by Pseudomonas aeruginosa), periodontitis, gingivitis, chronic wounds, infective endocarditis, infections associated with medical devices.

37. Composition according to any one of the preceding claims 35-36, characterized in that the biofilm disease is caused by a Candida auris biofilm.

38. Composition according to any one of the preceding claims 35-37, characterized in that it comprises at least one cyclic oligosaccharide as encapsulating agent, at least one antiseptic active ingredient; in which the encapsulating agent and the active ingredient form an inclusion compound, in which the composition is used as a coating on a medical device for use in the preventive treatment of biofilm-mediated medical device-associated infections in an individual.

39. Composition according to the preceding claim, wherein the medical device-associated infection is caused by Candida auris; preferably said medical device-associated infection is a catheter-associated infection.

40. Composition according to any one of the preceding claims 35-39, characterized in that the molar ratio between the antiseptic active ingredient and the encapsulating agent ranges from 8:1 to 1:

10.

41. Composition, according to the previous claim, characterized by presenting a molar ratio between the antiseptic active ingredient and encapsulating agent that varies from 1:1 to 1:8; preferably from 1:2 to 1:

4.

42. Composition according to any one of the preceding claims 35-41, characterized in that it further comprises a free cyclic oligosaccharide.

43. Composition according to any one of the preceding claims 35-42, characterized in that the mass of free cyclic oligosaccharide, relative to the total mass of the composition, varies between 44. Composition according to any one of the preceding claims 35-43, characterized in that it comprises encapsulating agents selected from a list consisting of: betacyclodextrin, alphacyclodextrin, or gammacyclodextrin and / or their structural variations or mixtures thereof.

45. Composition according to any one of the preceding claims 35-44, characterized in that the concentration of the antiseptic active ingredient varies from 0.005% to 30% (m / v); preferably 0.01% - 10% (m / v).

46. ​​Composition according to any one of the preceding claims 35-45, characterized in that the antiseptic active ingredient is cationic, anionic, zwitterionic, or neutral; and / or selected from a list consisting of classes of: b / s-biguanide, antimicrobial agent, essential oil, hydrolate, or mixtures thereof; preferably wherein the antimicrobial agent is an antibiotic, antifungal agent, antiparasitic agent, or mixtures thereof.

47. Composition according to the previous claim, characterized in that ab / s-biguanide is selected from a list consisting of: chlorhexidine, or its acetate, gluconate, or digluconate salts, or mixtures thereof.

48. Composition according to claim 46, characterized in that the antibiotic is selected from a list consisting of: tetracycline, beta-lactam; aminoglycoside; macrolide; fluoroquinolone; sulfonamide; oxazolidinone; glycopeptide; streptogramin; rifamycins; or mixtures thereof.

49. Composition according to claim 46, characterized in that the antifungal agent is selected from a list consisting of: azoles, polyenes, echinocandins, or mixtures thereof.

50. Composition, according to claim 46, characterized in that the essential oil is selected from a list consisting of: essential oil of natural bases such as thyme, eucalyptus, oregano, basil, mint, peppermint, levantia, horsetail, mint, rosemary, rosemary of the field, pequi, geranium, citronella, palmarosa, pitanga, hibiscus, cypress, tea tree, ginger, lemongrass, ora-pro-nóbis, moringa, cinnamon, muira puama, amapá, lemongrass or propolis, or mixtures thereof.

51. Composition, according to the previous claim, characterized in that the concentration of the essential oil varies between 0.05% and 99.00% (m / m).

52. Composition according to any one of the preceding claims 35-51, characterized in that the composition further comprises the addition of an organic acid and / or an alcohol with a saturated or unsaturated chain; preferably wherein the main chain of the organic acid and / or the alcohol with a saturated or unsaturated chain has a number of carbon atoms between 1 and 10; more preferably between 2 and 8.

53. Composition according to any one of the preceding claims 35-52, characterized in that it further comprises at least one of the following excipients: humectant, emulsifier, preservative, thickener, sweetener, stabilizer, colorant, antioxidant, surfactant, drug delivery vehicle, or flavorings, or mixtures thereof.

54. Composition according to the previous claims, characterized in that the excipient concentration varies between 0.02% to 99.00% (m / m); preferably 0.5% to 10% (m / m).

55. Composition according to any one of the preceding claims 35-54, characterized in that said composition further comprises an organic matrix; preferably cellulosic material; more preferably cellulosic resin.

56. Composition according to any one of the preceding claims 35-55, characterized in that said composition is in the form of an emulsion, aqueous solution, powder, paste, wet gel, oil lubricant, xerogels, aerosols, spray, foam, tablets, or capsules; preferably emulsion.

57. A coated surface or coated article, characterized in that the coating is on a medical device and comprises the composition described in the preceding claims 35-56, for use in the preventive treatment of biofilm-mediated medical device-associated infections in an individual.

58. Coated surface or article for use according to the preceding claim, characterized in that the coated surface or article additionally comprises at least 0.01% (w / v) of the composition described in the preceding claims 35-56.

59. Coated surface or article for use according to claims 57-58, characterized in that the coated surface or article is a medical device, preferably selected from the list consisting of a catheter, a syringe, a stent, a tube, a medical packaging, a dialysis device, a dental prosthesis, a dental implant, an orthodontic device, a mask or clothing.

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