Composition of natural extracts having antibacterial or bacteriostatic activity also for gram-negative bacteria

Abstract

To provide a mixture of natural origin having a reduced environmental impact as antibacterial, antibacterial proliferative, bacteriostatic, microbicidal, anti-mold, anti-yeast, antifungal or antimycotic agent against Gram-positive and / or Gram-negative bacteria, and use thereof.SOLUTION: A mixture M of natural origin comprising an usnic acid and / or a salt thereof, preferably an usnic acid sodium salt, in the racemic or dextrorotatory D(+) form is provided. Furthermore, the present invention provides an inclusion compound (ci) comprising, or alternatively consisting of: (i) a D-usnic acid as an enantiomer, or a salt thereof, or mixtures thereof, of natural origin, and (ii) beta-cyclodextrins. The present invention also provides the use of the mixture M and / or the inclusion compound (ci) as an antibacterial, antibacterial proliferative, bacteriostatic, microbicidal, anti-mold, anti-yeast, antifungal or antimycotic agent, preferably against Gram-positive and / or Gram-negative bacteria.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a mixture M comprising (a) usnic acid and / or (b) a salt thereof, preferably the usnic acid and / or its salt in racemic or dextrorotatory D(+) form, or consisting of them. Further, the present invention relates to a semi-finished product PS comprising the mixture M and a resin, preferably in the form of a semi-solid cream or paste, and to a finished product PF comprising the semi-finished product PS and a paint product, preferably in the form of a liquid or dispersion. The mixture M, the semi-finished product PS, and the finished product PF exhibit antibacterial activity, antibacterial growth inhibition, bacteriostatic activity, bactericidal activity, anti-mold activity, anti-yeast activity, anti-fungal activity, or anti-filamentous fungus activity, preferably against Gram-positive bacteria and / or Gram-negative bacteria, such as those having the scientific names of the genus Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia. Finally, the present invention relates to a method of imparting antibacterial, antibacterial growth inhibitory, bacteriostatic, bactericidal, anti-mold, anti-yeast, anti-fungal, or anti-filamentous fungus properties to a surface, preferably against Gram-positive and / or Gram-negative bacteria, the method comprising applying the mixture M, or the semi-finished product PS, or the finished product PF to the surface by spray, roller, or brush techniques.

[0002] Furthermore, the present invention relates to an inclusion compound (ci) comprising, or consisting of, (i) D-usnic acid as an enantiomer, or a salt thereof, or a mixture thereof, which is of natural origin, and (ii) beta-cyclodextrin. The inclusion compound (ci) has antibacterial or bacteriostatic activity against both Gram-positive pathogenic bacteria and Gram-negative pathogenic bacteria, for example, those having the scientific names of the genus Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli. Furthermore, the present invention relates to the use of the inclusion compound (ci) as an antibacterial or bacteriostatic agent against Gram-negative bacteria and Gram-positive bacteria. Furthermore, the present invention relates to a liquid composition comprising, or consisting of, (a) the inclusion compound (ci); (b) an acrylic resin, a polyurethane resin, or an acrylic-polyurethane resin, or a mixture thereof; (c) optionally a pigment or an opacifier; and (d) water. Furthermore, the present invention relates to the use of the liquid composition as a paint or an architectural coating for surfaces and walls, preferably having antibacterial or bacteriostatic properties against both Gram-positive and Gram-negative pathogenic bacteria, for example, those having the scientific names of the genus Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli. Finally, the present invention relates to the use of cyclodextrin, preferably beta-cyclodextrin, such as (2-hydroxypropyl)-β-cyclodextrin, as a selective complexing agent for D-usnic acid, or a salt thereof, or a mixture thereof, from a racemic mixture of usnic acid, which latter is also obtained starting from natural substances by the extraction method which is the subject of the present invention.

Background Art

[0003] Pathogenic microorganisms, also called pathogens, are biological substances that cause the onset of diseases in host organisms. They are distinguished among viruses; prokaryotes: bacteria; eukaryotes: fungi, and protozoa. The pathogenicity, or the general ability to determine a diseased state, is defined by two factors: (i) virulence, which indicates the ability to cause more or less disease; (ii) invasiveness, that is, the ability to invade and grow in the host's tissues. Next, invasiveness is determined by factors such as adhesiveness, that is, the ability of the pathogen to bind to the receptor sites of host cells by its outer surface structures; the production of extracellular enzymes that promote the destruction of host tissues; the production of anti-phagocytic substances or the presence of anti-phagocytic capsules that enable the pathogen to counter the host's defense mechanisms. The increasing occurrence of nosocomial infections (infections associated with care in healthcare facilities) due to the spread of multi-drug resistant microorganisms has been the subject of research and investigation for many years. Many scientific studies have shown that the surfaces of the hospital environment play a prominent role in the contamination, persistence, and spread of various microorganisms in the hospital environment, and therefore such surfaces serve as a persistent reservoir of pathogens in inpatient facilities. In the hospital environment, as well as in other environments, there is a need to limit the harmful bacterial load (among other things) and to enable patients to stay in an aseptic environment as much as possible. The same can apply to schools, kindergartens, playgrounds, or public places, such as supermarkets and shopping malls, where there is a very high bacterial load due to the presence of a large number of people very frequently. Furthermore, infectious (pathogenic) microorganisms have evolved into strains that can withstand most of the antibiotics previously available on the market. Therefore, in order to make it difficult or minimize the growth of microorganisms on treated surfaces, it can be very useful to treat surfaces made of, for example, cloth, leather, wood, glass, plastic, steel, linoleum, or the walls and floors of concrete with active substances or active compounds that are still unknown to living microorganisms, including drug-resistant microorganisms. Examples of surfaces to be treated can be found, but are not limited to, for example, in clinics, emergency departments, hospitals, dental clinics, playgrounds, kindergartens, schools, or in public or private facilities, or in, for example, supermarkets and shopping malls, or in playgrounds, in washrooms and toilet facilities.

[0004] In Italy, the probability of contracting an infectious disease during hospitalization is 6%, with many cases in the range of 450,000 to 700,000 per year, and an estimated annual death toll of approximately 7,800. The latter statistic brings Italy to an unfortunate first place among European countries. Currently, surface environmental contamination is being combated using detergent compounds or synthetic bactericides that are not effective in preventing short-term recontamination (within 30 minutes of disinfection) or are otherwise unsuitable and have a significant environmental impact.

Summary of the Invention

Problems to be Solved by the Invention

[0005] Therefore, there is a felt need to obtain surface treatments, active compounds, and active compositions that have a reduced environmental impact and are optionally completely of natural origin. Thus, if it is impossible to keep environmental surfaces hygienic over a long period of time, sanitation using only synthetic agents cannot guarantee a healthy and safe environment in hospitals or kindergartens or schools. Therefore, in public and private environments and spaces, such as hospitals or kindergartens or schools, there is a need to obtain treatments, active compounds, and active compositions with a reduced environmental impact that can reduce the pathogenic bacterial load or fight against the pathogenic bacterial load, or effectively fight against the contamination, persistence, and transmission of pathogenic bacteria and prevent the spread and / or acquisition of resistance of pathogenic bacteria.

Means for Solving the Problems

[0006] After years of diligent research and development activities, the applicant has developed a mixture M, a semi-finished product PS containing the mixture M and a resin, a finished product PF containing the semi-finished product PS and a paint product, an inclusion compound and its composition, which can achieve appropriate responses to existing limitations, drawbacks, and problems. Further, the applicant has developed a surface treatment method that enables the surface treated with the mixture M, the semi-finished product PS containing the mixture M and a resin, the finished product PF containing the semi-finished product PS and a paint product, the inclusion compound and its composition to be antibacterial, antibacterial growth-promoting, bacteriostatic, bactericidal, antifungal, anti-yeast, anti-fungal, or anti-filamentous fungal, preferably against Gram-positive and / or Gram-negative bacteria.

[0007] Examples of surfaces on which the mixture M, the semi-finished product PS containing the mixture M and a resin, the finished product PF containing the semi-finished product PS and a paint product, the inclusion compound and its composition can be applied are, for example, horizontal or vertical surfaces, such as surfaces made of concrete, lime board or gypsum board, linoleum, or polyvinyl chloride (PVC), polyamide (PA), polyethylene (PE), polyester (PES), or polyethylene terephthalate (PTF), such as floors, walls, or ceilings. Surfaces of this type can be found, for example, in clinics, emergency departments, hospitals, dental clinics, sports fields, kindergartens, schools, or in washrooms and toilet facilities present in, for example, public or private facilities, or in, for example, supermarkets and shopping malls, or sports fields. Alternatively, they may be surfaces made of cloth, non-woven fabric (NWF), natural leather, artificial or synthetic leather, hides, wood, glass, plastic, polymer, aluminum, steel, or linoleum.

[0008] The object of the present invention is a mixture M containing usnic acid and / or its salt, preferably sodium usnate, wherein the usnic acid and / or its salt is preferably a racemate or a naturally occurring dextrorotatory D(+)-type, and the mixture M has the characteristics as reported in the appended claims.

[0009] The object of the present invention is the use of said mixture M as being antibacterial, antibacterial growth promoting, bacteriostatic, bactericidal, antimold, antiyeast (e.g., Candida), antifungal, or antifilamentous (e.g., Saccharomycetes), preferably against Gram-positive and / or Gram-negative bacteria, such as those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli, etc., which use has the characteristics as reported in the appended claims.

[0010] The object of the present invention is a method for making a surface antibacterial, antibacterial growth promoting, bacteriostatic, bactericidal, antimold, antiyeast, antifungal, or antifilamentous, preferably against Gram-positive and / or Gram-negative bacteria, such as those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli, etc., which method realizes the application of said mixture M to said surface by spray, roller, or brush techniques and has the characteristics as reported in the appended claims.

[0011] Preferably, the surface to be treated can first be pretreated to enhance the adhesion, stability, or effectiveness of said mixture M on the surface. The pretreatment may be, for example, of a mechanical type, such as mechanical abrasion of the surface using emery, or of a chemical type, such as by applying an impregnating solution or a coating film, such as a polymer film, or a paint, or a fixing agent or an adhesive.

[0012] The object of the present invention is a semi-finished product PS containing said mixture M and a resin, which semi-finished product has the characteristics as reported in the appended claims. As an example, the resin is known to those skilled in the art of, for example, varnishes, enamels, and paints (aqueous or organic solvent-based; transparent, glossy, or opaque, or colored), such as one-component or two-component resins. The resin is added to said mixture M by procedures and equipment known to those skilled in the art.

[0013] The object of the present invention is the use of the semi-finished product PS as an antibacterial, antibacterial growth-promoting, bacteriostatic, bactericidal, anti-mold, anti-yeast (e.g., Candida genus), antifungal, or anti-filamentous fungus (e.g., Saccharomycetes class) agent, preferably against Gram-positive and / or Gram-negative bacteria, such as those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli, etc., which has the characteristics as reported in the appended claims.

[0014] The object of the present invention is a method for making the surface antibacterial, antibacterial growth-promoting, bacteriostatic, bactericidal, anti-mold, anti-yeast, antifungal, or anti-filamentous fungus against Gram-positive and / or Gram-negative bacteria, such as those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli, etc. The method realizes the application of the semi-finished product PS to the surface by spray, roller, or brush technology and has the characteristics as reported in the appended claims.

[0015] Preferably, the surface to be treated can be pretreated first to enhance the adhesion, stability, or effectiveness of the semi-finished product PS on the surface. The pretreatment may be, for example, of a mechanical type, such as mechanical abrasion of the surface using emery, or of a chemical type, such as by applying an impregnating solution or a coating film, such as a polymer film, or a paint, or a fixing agent or an adhesive.

[0016] The object of the present invention is a finished product PF that includes the semi-finished product PS and a paint product and has the characteristics as reported in the appended claims. As an example, the paint product is known to those skilled in the technical fields of, for example, varnishes, enamels, and paints (aqueous or organic solvent-based; transparent, glossy, or opaque, or colored). The paint product is added to the semi-finished product PS by procedures and equipment known to those skilled in the art.

[0017] The object of the present invention is the use of the finished product PF as an antibacterial, antibacterial growth-promoting, bacteriostatic, bactericidal, antifungal, anti-yeast (e.g., Candida genus), antifungal, or anti-filamentous fungal (e.g., Saccharomycetes class) agent, preferably against Gram-positive and / or Gram-negative bacteria, such as those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli, etc., having the characteristics as reported in the appended claims.

[0018] The object of the present invention is a method for making the surface antibacterial, antibacterial growth-promoting, bacteriostatic, bactericidal, antifungal, anti-yeast (e.g., Candida genus), antifungal, or anti-filamentous fungal (e.g., Saccharomycetes class) against Gram-positive and / or Gram-negative bacteria, such as those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli, etc., by realizing the application of the finished product PF to the surface by spray, roller, or brush techniques, having the characteristics as reported in the appended claims.

[0019] In one embodiment, it is also possible to first perform a pretreatment on the surface to be treated to enhance the adhesion, stability, or effectiveness of the finished product PF on the surface. The pretreatment may be, for example, of a mechanical type, such as mechanical abrasion of the surface using emery, or of a chemical type, such as by applying an impregnating solution or a coating film, such as a polymer film, or a paint, or a fixing agent or an adhesive.

[0020] In one embodiment, the finished product PF, preferably in the form of a liquid or dispersion, comprises the semi-finished product PS and a paint product, such as a colored, opaque, or transparent paint product. The paint product may be, for example, a water-based or organic solvent-based varnish, enamel, or paint. The combination or association of the semi-finished product PS, preferably in the form of a cream or semi-solid paste, and a varnish or enamel or paint, preferably in the form of a liquid or dispersion, results in a finished product in the form of a colored, opaque, or transparent paint, or a finished product in the form of a colored, opaque, or transparent enamel, or a finished product in the form of a colored, opaque, or transparent paint. The latter finished product in the form of a varnish, enamel, or paint, in order to impart, for example to surfaces made of wood or steel or glass or concrete in a hospital, antibacterial, antibacterial growth-inhibiting, bacteriostatic, bactericidal, antifungal, anti-yeast, antifungal, or anti-filamentous fungal properties, preferably against Gram-positive and / or Gram-negative bacteria, can be applied to a optionally pre-treated surface using spray or roller or brush techniques.

[0021] In another embodiment, the semi-finished product PS or the finished product PF can be added, for example, to a polymer material (such as PVC, PE, or PTF) commonly used to prepare a coating film or a colored, opaque, or transparent film. The polymer film or film material is then placed and fixed on the surface of a table, or kitchen shelf, or wall, made of, for example, wood or plastic or aluminum or steel, using, for example, glue or by high-temperature heating.

[0022] In another embodiment, the semi-finished product PS or the finished product PF can be added, for example, to a solution or cream commonly used to treat or polish natural or synthetic leather of, for example, a chair or a footstool chair.

[0023] Furthermore, an object of the present invention is an inclusion compound (ci) comprising, or consisting of, (i) D-usnic acid, or a salt thereof, or a mixture thereof, as an enantiomer, preferably as a pure enantiomer, and (ii) beta-cyclodextrin, and having the characteristics as defined in the appended claims. The D-usnic acid compound (i) is of natural origin since it is extracted by a process starting from natural materials.

[0024] Furthermore, an object of the present invention is the use of the inclusion compound (ci) as an antibacterial or bacteriostatic agent against Gram-negative and Gram-positive bacteria, having the characteristics as defined in the appended claims.

[0025] Furthermore, an object of the present invention is a liquid composition comprising, or consisting of, (a) the inclusion compound (ci); (b) an acrylic resin, a polyurethane resin, or an acrylic-polyurethane resin, or a mixture thereof; (c) optionally a pigment or an opacifier; and (d) water, and having the characteristics as defined in the appended claims.

[0026] Furthermore, an object of the present invention is the use of the liquid composition as a paint for surfaces and walls or an architectural coating, having the characteristics as defined in the appended claims, preferably as an architectural coating antibacterial or bacteriostatic against both Gram-positive pathogenic bacteria and Gram-negative pathogenic bacteria.

[0027] Finally, an object of the present invention is the use of cyclodextrin, preferably beta-cyclodextrin, such as (2-hydroxypropyl)-β-cyclodextrin, as a selective complexing agent for D-usnic acid, or a salt thereof, or a mixture thereof, having the characteristics as defined in the appended claims.

[0028] Here, the present invention will be described with reference to the accompanying drawings shown as non-limiting examples.

Brief Description of the Drawings

[0029]

Figure 1

Figure 2

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Figures 7 - 10

Figure 11

Figure 12

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Figure 14

Embodiments for Carrying Out the Invention

[0030] Accordingly, the object of the present invention is to provide an inclusion compound (ci) comprising, or consisting of, (i) D-usnic acid, or a salt thereof, or a mixture thereof, as an enantiomer, preferably as a pure enantiomer, and (ii) beta-cyclodextrin. The D-usnic acid compound (i) is of natural origin since it is extracted by a process which is also the subject of the present invention starting from natural materials. The (ii) beta-cyclodextrin is also of natural origin. Therefore, the inclusion compound (ci) is also of natural origin. Advantageously, the inclusion compound (ci) has bacteriostatic or antibacterial activity against both Gram-positive and Gram-negative pathogenic bacteria.

[0031] In the context of the present invention, the expression "inclusion compound" refers to a chemical structure of the same type as a chemical complex in which a compound (host) has pores (e.g., 1, or 2, or 3 pores, preferably 1) of specific dimensions which are equal to or different from each other, and in which a molecule (e.g., 1, or 2, or 3 molecules, preferably 1), which is a second compound (guest), having dimensions similar to those of the respective pores can be assigned, arranged, or fixed, and the host and the guest are generally non-covalently bonded by intermolecular forces such as van der Waals forces. Cyclodextrin is a natural cyclic oligosaccharide formed from 6, 7, or 8 D-(+)-glucopyranose monomers linked to each other by alpha1-4 glucoside bonds and closed in a ring, and has pores of specific sizes which are equal to or different from each other (e.g., 1 or 2 pores). The cyclodextrin (ii) of the present invention forms a molecular cage defining a lipophilic pore capable of accepting the D-usnic acid, or a salt thereof, or a mixture thereof (i) as an enantiomer of the present invention.

[0032] Preferably, the cyclodextrin (ii) used in the inclusion compound (ci) is selected from the group consisting of, or consisting of, alpha-cyclodextrin, beta-cyclodextrin, gamma-cyclodextrin, and mixtures thereof. More preferably, the cyclodextrin is (ii) beta-cyclodextrin.

[0033] In one embodiment, (ii) the cyclodextrin is selected from beta-cyclodextrin. (ii) The cyclodextrin comprises, or consists of, (2-hydroxypropyl)-β-cyclodextrin (CAS number 128446-35-5).

[0034] In fact, (2-hydroxypropyl)-β-cyclodextrin, among other things, has been found to be, advantageously, a selective complexing agent for D-usnic acid, or a salt thereof, or a mixture thereof, from the racemic mixture (or racemate) of usnic acid obtainable by the process of the invention.

[0035] Racemic usnic acid (CAS number 125-46-2) is a bioactive secondary metabolite of lichens. The large-scale use of said usnic acid has always been limited because of its low solubility in water (0.06 mg / cm at room temperature of 20 °C and a pressure of 1 atm). 3 )

[0036] Therefore, the solubility of usnic acid in water has always been, and still is, a major limitation to its use. Furthermore, with regard to the effectiveness of usnic acid (or its related salts) in terms of antibacterial activity, the inventors of the present invention have noticed that it depends on both the origin (natural or synthetic) of the usnic acid and the type of isomer used (levorotatory (−) and / or dextrorotatory (+)). It has been found that the naturally occurring dextrorotatory form (+) of the genus Usnea is more stable, effective, and active than the synthetically derived dextrorotatory form (+).

[0037] After arduous and extensive research activities, the inventors of the present invention have surprisingly found that the solubility in water of the enantiomer of D-usnic acid, or a salt thereof, or a mixture thereof (i) can be increased by several orders of magnitude by forming an inclusion compound (ci) (considering the same temperature of 20 °C and a pressure of 1 atm, for example, about 4.2 mg / cm 3up to). As described above, in such a compound (ci), the lipophilic pores of cyclodextrin (host) reversibly accept D-usnic acid, or a salt thereof, or a mixture thereof (i) (guest) through non-covalent interactions. In fact, during the formation of the inclusion compound (ci), no covalent bond is formed and no covalent bond is broken. The mechanism that promotes the formation of the inclusion compound, at least mainly, is the release of solvent molecules (preferably water molecules) from the cyclodextrin pores (ii), which is a highly entropic exchange reaction. Thanks to this host / guest interaction (reversible electrostatic chemical bond), the inventors of the present invention surprisingly found that D-usnic acid, or a salt thereof or a mixture thereof (i) is not trapped / bound in the inclusion compound or cannot perform its function. On the contrary, it is easily released from the lipophilic pores of its host and is thus easily available to perform its activity. Furthermore, the inclusion compound (ci) makes D-usnic acid (or a salt thereof) compatible with an aqueous solution or an aqueous dispersion or an aqueous suspension. When the aqueous solution or dispersion or suspension containing the inclusion compound (ci) is applied to the surface such as the wall or floor inside a hospital or a kindergarten or a school by spraying or mechanically, the acid or a salt thereof contained in the inclusion compound (ci) can be arranged, adhered to, and coat the surface uniformly and homogeneously as if it were a coating paint.

[0038] Said D-usnic acid (i) as an enantiomer, preferably as a pure enantiomer, is of natural origin and can be associated with the chemical structure of the corresponding synthetic compound having the CAS number 7562-61-0, i.e., the chemical structure of the dextrorotatory enantiomer of said acid. The D-usnic acid as a pure enantiomer of the present invention is soluble in chloroform and ethyl acetate. It is moderately soluble in ethanol but insoluble in water. Said D-usnic acid as a pure enantiomer has a melting point ranging from 192°C to 204°C, a flash point of 223°C, and a boiling point of 605°C. Preferably, said D-usnic acid salt as a pure enantiomer is a sodium salt. Said inclusion compound (ci) preferably contains solid particles of D-usnic acid as a pure enantiomer, or its salt, or a mixture thereof (i). More preferably, said solid particles have an average particle distribution ranging from 0.01 μm to 50 μm, preferably from 0.1 μm to 30 μm, more preferably from 0.15 μm to 20 μm, and even more preferably from 0.2 μm to 15 μm. The average particle distribution was determined and measured using a laser diffraction method in accordance with the GB / T 19077-2016 standard, for example, by a Malvern Mastersizer 3000 device. It is intended to refer to the said standard in the version effective on the priority date of the patent application of the present invention. Preferably, said solid particles have an average particle distribution such that D10 = 0.236 μm, D50 = 1.570 μm, and D90 = 31.800 μm. In an embodiment of the present invention, said solid particles have a distribution according to Figure 2. An aqueous dispersion of D-usnic acid as a pure enantiomer is obtained when said solid particles are dispersed in the aqueous phase of a liquid composition.

[0039] D-usnic acid, or its salt, or a mixture thereof (i) is advantageously natural and non-synthetic D-usnic acid, preferably extracted from lichens. There are various methods for classifying lichens. One of these methods is to examine the various forms of growth. - Fruticose lichens. Species of lichens belonging to this group are Letharia vulpina, or those belonging to the genus Usnea, also known as bearded lichen, and the genus Ramalina. - Foliose lichens. This type of lichen includes lichens of the genera Parmelia, Collema, Physcia, Physconia, and Xanthoria. - Crustose lichens. - Gelatinous lichens. - Squamulose lichens. Some lichens that can be seen in this category are Catapyrenium psoromoides, Cladonia coniocraea, Cladonia fimbriata, Cladonia macilenta, Cladonia pyxidata, and Normandina pulchella.

[0040] Lichens are preferably selected from the group consisting of, or consisting of, the genus Usnea, Cladonia, Pertusaria, Parmotrema, Ramalina, Umbilicaria, Parmelia, Cetraria, and combinations thereof, more preferably from the genus Usnea, and even more preferably from Usnea Longissima Ash. by the extraction method which is the subject of the present invention.

[0041] Attached Figure 1 schematically shows a flowchart of an embodiment of a method for obtaining naturally occurring D-usnic acid according to a possible embodiment thereof. According to such an embodiment of this method, usnic acid in dried form is obtained after the following steps: (a.1) A plant material selected from lichens, preferably a group consisting of or comprising Usnea, Cladonia, Cetraria, Parmelia, Physcia, Yamabikohori, Umenokigoke, Honekinoori, and combinations thereof, more preferably Usnea, and even more preferably a group consisting of Nagasaruoga, is softened and extracted with an organic solvent, preferably a solvent selected from the group consisting of benzene, hexane, acetone, chloroform, trichloroethylene, or an alcohol-based solvent, and even more preferably ethanol, to obtain an extraction solution, and the extraction solution is concentrated to obtain a concentrated extraction solution and a residual solvent; (a.2) Crystallizing and filtering the concentrated extraction solution obtained from step (a.1) to obtain a crystallized and filtered extraction product; (a.3) Dissolving, filtering, and concentrating the crystallized and filtered extraction product obtained from step (a.2) to obtain a concentrated extract and a residual solvent; (a.4) Crystallizing, filtering, then drying and pulverizing the concentrated extract obtained from step (a.3) to obtain a dry pulverized extract of usnic acid having a titration concentration preferably contained in 80% - 99.9%, more preferably contained in 90% - 99.5%, and even more preferably contained in 95% - 98%.

[0042] The softening and extraction in step (a.1) are preferably carried out in an extraction tank made of preferably stainless steel and equipped with stirring means and heating means. Preferably, in the softening and extraction in step (a.1), a ratio of [weight of plant material]:[volume of organic solvent] contained in 10:1 - 1:50, preferably contained in 5:1 - 1:40, and even more preferably contained in 1:1 - 1:35 is used. The softening and extraction in step (a.1) are preferably carried out at a temperature contained in 10°C - 80°C, preferably contained in 20°C - 70°C, and even more preferably contained in 25°C - 60°C at ambient pressure.

[0043] The concentration of step (a.1) is preferably carried out in a concentrator (or evaporator), more preferably in a single-acting type, and even more preferably in a concentrator (evaporator) made of stainless steel.

[0044] In step (a.1), the thallus (buds or young branches) of the genus Sarothamnus (Sarothamnus nagasakianus) is used together with an ethyl acetate solvent, for example, in an amount of 350 Kg of plant parts and 2600 liters of solvent. Maceration is preferably carried out at a temperature of about 25 °C and a pressure of 1 atmosphere for a certain period of time included in 2 to 10 hours, preferably 4 to 8 hours, for example 5 to 6 hours. Maceration can be carried out in a reactor equipped with means for stirring, heating, and recycling the liquid. Basically, maceration is carried out by continuously recirculating the distillate (solvent) onto the plant parts. The extraction carried out as one step is carried out at a temperature of about 25 °C and a pressure of 1 atmosphere. The concentration of the extraction solvent containing usnic acid extracted from the plant parts is carried out taking into account the boiling point of ethyl acetate, which is about 77.1 °C, which may also affect the extraction pressure. A thick concentrated liquid and a solvent recovery product are obtained almost completely.

[0045] In the crystallization and filtration in step (a.2) for obtaining the crystallized and filtered extract product following step (a.1), an organic solvent selected from the group consisting of or consisting of benzene, hexane, acetone, chloroform, trichloroethylene, or an alcohol-based solvent, more preferably ethanol, is preferably used. In the crystallization and filtration in step (a.2), a volume ratio of [concentrated extract solution]:[organic solvent] contained in 10:1 to 1:40, preferably contained in 5:1 to 1:30, more preferably contained in 1:1 to 1:20, is preferably used. In the crystallization in step (a.2), the concentrated extract solution obtained from step (a.1) is preferably cooled, more preferably at a temperature contained in 1°C to 20°C at ambient pressure, and even more preferably at a temperature contained in 5°C to 15°C at ambient pressure to promote crystallization. At the end of step (a.2), a crystalline material in an amount of about 20 Kg with a purity of at least 80%, 85% - 90% is obtained starting from about 350 Kg of plant parts.

[0046] In step (a.3) following step (a.2), the crystallized and filtered extract product obtained from step (a.2) is dissolved, filtered, and concentrated to obtain a concentrated extract and a residual solvent. In step (a.3), an organic solvent, more preferably an organic solvent selected from the group consisting of or consisting of benzene, hexane, acetone, chloroform, trichloroethylene, or an alcohol-based solvent, even more preferably ethanol, is preferably used. In the dissolution in step (a.3), a ratio of [weight of crystallized and filtered extract product]:[volume of organic solvent] contained in 10:1 to 1:40, preferably contained in 5:1 to 1:30, more preferably contained in 1:1 to 1:20, is preferably used. In step (a.3), they are dissolved in 2 × 20 Kg of chloroform to obtain 20 Kg of usnic acid with a minimum purity of 98%.

[0047] In step (a.4) following step (a.3), the concentrated extract obtained from step (a.3) is crystallized, filtered, and then dried and pulverized to obtain a dried and pulverized extract of usnic acid. In the crystallization of step (a.4), an organic solvent, more preferably an organic solvent selected from the group consisting of or consisting of benzene, hexane, acetone, chloroform, trichloroethylene, or an alcohol-based solvent, and even more preferably ethanol, is preferably used. In the crystallization of step (a.4), a ratio of [weight of concentrated extract]:[volume of organic solvent] contained in 10:1 to 1:40, preferably contained in 5:1 to 1:30, and even more preferably contained in 1:1 to 1:20, is preferably used. In the crystallization of step (a.4), the concentrated extract obtained from step (a.3) is preferably cooled, and more preferably at a temperature contained in 1°C to 20°C at ambient pressure, and even more preferably at a temperature contained in 5°C to 15°C at ambient pressure to promote crystallization. The drying in step (a.4) is preferably carried out until the residual solvent content is contained in 0.5% to 10% by weight, preferably contained in 1% to 5% by weight, and even more preferably contained in 1.5% to 3% by weight, based on the total weight of the dried extract of usnic acid. Preferably, the pulverization in step (a.4) is carried out by a mill, and more preferably by a rotary ball mill. The drying of the filtered and crystallized solid obtained from step (a.4) is completed when a residual solvent content corresponding to about 2% to 5% by weight based on the initial weight remains. A plate dryer (without using vacuum pressure) is used while circulating air at a temperature of about 95°C to 99°C. The pulverized solid has an average particle distribution contained in 20 mesh to 40 mesh and contains 98% by weight of usnic acid (HPLC by the Sigma Aldrich method). Starting from 2 × 350 Kg of plant parts (starting materials) at the beginning of the process, a material (dried solid) with a yield of about 3% to 4% is obtained at the end of the process, which corresponds to about 14 Kg to 28 Kg of usnic acid (13.72 Kg to 27.44 Kg) with a content of 98% by weight. The obtained usnic acid is usnic acid with a purity of 99.9% of the D(+) form, or a racemic form.

[0048] After obtaining a dry ground extract of usnic acid as a racemic mixture (step (a.4)), the dry extract is selectively complexed with cyclodextrin, preferably beta-cyclodextrin, to obtain the inclusion compound (ci). Preferably, the selective complex formation is obtained by coprecipitation of D-usnic acid, or a salt thereof, or a mixture thereof (i) and cyclodextrin (ii). The inclusion compound (ci) is preferably obtained by coprecipitation of D-usnic acid, or a salt thereof, or a mixture thereof (i) and cyclodextrin (ii), preferably beta-cyclodextrin. More precisely, cyclodextrin (ii) is first dissolved in water or another suitable aqueous solvent, and while maintaining the aqueous solution containing cyclodextrin (ii) under stirring, the dry ground extract of usnic acid from step (a.4) is then added. In the presence of a sufficiently high concentration of cyclodextrin (ii) in the solution, precipitation of the inclusion compound (ci) will start as the complex formation reaction of D-usnic acid, or a salt thereof, or a mixture thereof (i) by cyclodextrin (ii) proceeds gradually. Preferably, in order to initiate precipitation, the solution containing the inclusion compound (ci) may need to be cooled to a temperature included between 1 °C and 18 °C, preferably under stirring. The inclusion compound (ci) may be collected by decantation, centrifugation or filtration. The inclusion compound (ci) is preferably a water-soluble inclusion body or an inclusion body suspendable in water, and when the D-usnic acid, or a salt thereof, or a mixture thereof (i) comes into contact with the cyclodextrin (ii), the D-usnic acid, or a salt thereof, or a mixture thereof (i) as the pure enantiomer is received in the cavities of the inclusion body. D-usnic acid, or a salt thereof, or a mixture thereof (i) and cyclodextrin (ii), preferably beta-cyclodextrin, are preferably present in the inclusion compound (ci) in a weight ratio included between 3:1 and 1:3, preferably included between 2:1 and 1:2, more preferably included between 1.5:1 and 1:1.5, and even more preferably in a weight ratio of 1:1. When using (2-hydroxypropyl)-β-cyclodextrin, the weight ratio with D-usnic is 1:1.The inclusion compound (ci) is preferably used as an antibacterial or bacteriostatic agent against both Gram-negative and Gram-positive pathogenic bacteria, preferably against Gram-negative bacteria for which the inclusion compound (ci) has been found to be particularly effective.

[0049] Preferably, the Gram-negative bacteria against which the inclusion compound (ci) exerts an antibacterial or bacteriostatic function are selected from the group consisting of, or including, Escherichia coli, Klebsiella spp., Acinetobacter baumannii, and combinations thereof. Preferably, the Gram-positive bacteria against which the inclusion compound (ci) exerts an antibacterial or bacteriostatic function are selected from the group consisting of, or including, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus spp., vancomycin-resistant Enterococcus (VRE), Actinobacteria, Actinobacter spp., Clostridium difficile, and combinations thereof. Preferably, in such use, the inclusion compound (ci) is added in the process of preparing products in the form of plastic films or layers, thermoplastic resins or polymers, polyethylene (PE), polyvinyl chloride (PVC), polyethylene terephthalate (PET), latex; or the inclusion compound (ci) is spread or disposed on the surface of the product in an amount of 0.1% to 20% by weight based on the weight of the product.

[0050] Furthermore, the object of the present invention is (a) the inclusion compound (ci); (b) an acrylic resin, a polyurethane resin, an acrylic-polyurethane resin, or a mixture thereof; (c) optionally a pigment or an opacifier; (d) water to be a liquid composition comprising, or consisting of, the above.

[0051] The liquid composition has bacteriostatic or antibacterial activity against both Gram-positive pathogenic bacteria and Gram-negative pathogenic bacteria, such as those having scientific names of the genus Klebsiella, Enterobacteriaceae, genus Enterobacter, genus Pseudomonas, and genus Escherichia coli. The liquid composition may be in the form of an aqueous solution, an aqueous dispersion, an aqueous suspension, or an aqueous emulsion.

[0052] In the composition, the acrylic resin (b) used in combination with the inclusion compound (ci) preferably contains monomers selected from the group consisting of acrylic acid, acrylic esters, methacrylic acid, methacrylic esters, styrene, vinyltoluene, vinyl acetate, vinyl esters of carboxylic acids having a carbon number higher than acetic acid, acrylonitrile, acrylamide, butadiene, ethylene, vinyl chloride, and mixtures thereof, or consists of them. More preferably, the acrylic resin (b) contains a methacrylic acid-styrene copolymer or consists of a methacrylic acid-styrene copolymer.

[0053] The optional pigment or opacifier (c) present in the liquid composition together with the inclusion compound (ci) and the acrylic resin (b) is preferably selected from the group consisting of iron oxide, titanium oxide, cobalt-based pigments, phthalates, azo dyes, and mixtures thereof. Preferably, the pigment or opacifier contains titanium dioxide or consists of titanium dioxide.

[0054] The water (d) present in the liquid composition together with the inclusion compound (ci), the acrylic resin (b), and the optional pigment or opacifier (c) is not particularly limited. Preferably, the water (d) is tap water, purified water, or deionized water.

[0055] The liquid composition preferably contains (a) an inclusion compound (ci) in an amount of 0.1% to 15% by weight, preferably 0.2% to 10% by weight, and even more preferably 0.3% to 7% by weight, based on the total weight of the liquid composition; (b) An amount of the acrylic resin, the polyurethane resin, or the acrylic-polyurethane resin, which is contained in an amount of 1% to 80% by weight, preferably 2% to 75% by weight, and even more preferably 5% to 70% by weight, based on the total weight of the liquid composition; (c) Optionally, an amount of the pigment or the opacifying agent, which is contained in an amount of 10% to 40% by weight, preferably 15% to 35% by weight, and even more preferably 20% to 30% by weight, based on the total weight of the liquid composition; (d) Water in an amount of 1% to 40% by weight, preferably 2% to 30% by weight, and even more preferably 3% to 22% by weight, based on the total weight of the liquid composition and contains.

[0056] The object of the present invention is the use of the liquid composition as a paint or a building coating, preferably as a coating or paint for stone walls, or as a coating or paint for walls and floors, for example for linoleum floors, more preferably as an antibacterial building coating or as a bacteriostatic agent against both Gram-positive bacteria and Gram-negative bacteria.

[0057] Finally, the object of the present invention is the use of cyclodextrin, preferably beta-cyclodextrin, preferably (2-hydroxypropyl)-β-cyclodextrin, as a selective complexing agent(s) for D-usnic acid, or a salt thereof, or a mixture (i) thereof, from a racemic mixture (or racemate) of naturally derived usnic acid.

[0058] Examples of surfaces onto which the mixtures or products of the present invention can be applied are horizontal or vertical surfaces such as concrete, lime board or gypsum board, linoleum, or polyvinyl chloride (PVC), polyamide (PA), polyethylene (PE), polyester (PES) or polyethylene terephthalate (PTF), for example floors, walls, or ceilings. This type of surface can be found, but is not limited to, for example, in clinics, emergency departments, hospitals, dental clinics, sports fields, kindergartens, schools, or in, for example, public or private facilities, or in, for example, supermarkets and shopping malls, or in sports fields, in washrooms and toilet facilities.

[0059] The object of the present invention is a mixture M comprising, or consisting of, (a) usnic acid of natural origin and / or (b) its related salts.

[0060] The (a) usnic acid of natural origin contained in the mixture M is a combination or association C / A of dextrorotatory natural usnic acid D(+) and levorotatory natural usnic acid L(-).

[0061] In the context of the present invention, the term "combination" is used, for example, to indicate that dextrorotatory natural usnic acid D(+) and levorotatory natural usnic acid L(-) are both present in contact with each other prior to their use, while in the context of the present invention, the term "association" is used, for example, to indicate that dextrorotatory natural usnic acid D(+) and levorotatory natural usnic acid L(-) are separated from each other prior to their use and can come into contact with each other during their use. The meanings of "combination" and "association" of the present invention between substances are also applicable to, for example, usninate salts, as well as other substances or compounds used in the present invention.

[0062] The terms "natural" or "naturally derived" or "natural usnic acid or usninate salt or naturally derived usnic acid or usninate salt" are used to indicate that the usnic acid or usninate salt is obtained from plants, particularly plants of the family Parmeliaceae, genus Parmelia.

[0063] Preferably, the dextrorotatory form D(+) is present in the (a) naturally-derived usnic acid in an amount of 0.1% to 99.9% by weight based on the total weight of the combination or association C / A, while the levorotatory form L(-) is present in the (a) naturally-derived usnic acid in an amount of 99.9% to 0.1% by weight based on the total weight of the combination or association C / A. For example, usnic acid may be present as a racemate of 50%(+) and 50%(-), or for example as 100% dextrorotatory form D(+).

[0064] The (b) salt of usnic acid contained in the mixture M is a salt of an alkali metal or an alkaline earth metal. Preferably, the (b) usnic acid salt may be present in an amount of 0.1% to 99.9% by weight based on the total weight of the combination or association C / A, which is a salt of the dextrorotatory form D(+) of usnic acid, and may be present in an amount of 99.9% to 0.1% by weight based on the total weight of the combination or association C / A, which is the levorotatory form L(-). For example, the usnic acid salt, preferably sodium usnic acid salt, may be present as a racemate of 50%(+) and 50%(-), or for example as dextrorotatory sodium usnic acid salt D(+).

[0065] The (a) naturally-derived usnic acid and the (b) its related salt are contained in the mixture M in a weight ratio of 1:10 to 10:1, preferably 1:5 to 5:1, and even more preferably 1:3 to 3:1, for example, in a weight ratio of 3:1, 2.5:1, 2:1, 1.5:1, or 1:1.

[0066] The mixture M may be in a solid or semi-solid state, in a dispersed or suspended form, in the form of a cream or paste or gel, or in a liquid state. Preferably, the mixture M may be in the form of flakes, granules, powders, pellets, or may be in an aqueous solution or a hydroalcoholic solution, or in an organic solvent. The (a) natural usnic acid and / or the (b) related salts thereof may be a solid in the form of a powder having an average particle size included in the range of 1 micron to 100 microns, preferably 5 microns to 50 microns, and even more preferably 10 microns to 20 microns.

[0067] Usnic acid can be represented, for example, as (+)-usnic acid 2,6-diacetyl-7,9-dihydroxy-8,9-dimethyldibenz[b,d]furan-1,3(2H,9bH)-dione; (+)-usnic acid derived from the genus Usnea; CAS: 7562-61-0, EC: 231-456-0. Sodium usninate can be represented, for example, as 2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyldibenzofuran-1,3(2H,9bH)-dione monosodium salt; CAS: 34769-44-3, EC: 252-2046. The purity of the (a) usnic acid and / or the (b) usninate is included in the range of 95% to 99.9%, preferably 96% to 99.5%, and even more preferably 97% to 98%, for example 98%.

[0068] The object of the present invention is a semi-finished product PS comprising the mixture M and a resin, preferably in the form of a semi-solid cream or paste.

[0069] The mixture M contains or consists of the (a) natural usnic acid and / or the (b) related salts thereof. Preferably, the mixture M is present in the semi-finished product PS in an amount by weight of 20% to 80%, preferably 35% to 65%, and even more preferably 40% to 50% based on the total weight of the semi-finished product PS, for example, in an amount of 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, or 49%.

[0070] In one embodiment, the mixture M contained in the semi-finished product PS contains only the (a) usnic acid. In this case, the (a) usnic acid is contained in an amount of 20% to 80% by weight, preferably 35% to 65% by weight, and even more preferably 40% to 50% by weight based on the total weight of the semi-finished product PS, and is present in the semi-finished product PS in an amount of, for example, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, or 49%.

[0071] In another embodiment, the mixture M contained in the semi-finished product PS contains both the (a) usnic acid and the (b) its related salt, preferably the sodium salt. In this case, the usnic acid is contained in an amount of 10% to 60% by weight, preferably 20% to 50% by weight, and even more preferably 30% to 40% by weight based on the total weight of the semi-finished product PS, and is present in the semi-finished product PS in an amount of, for example, 24% or 32%. On the other hand, the salt of the (b) usnic acid is contained in an amount of 5% to 50% by weight, preferably 10% to 40% by weight, and even more preferably 15% to 30% by weight based on the total weight of the semi-finished product PS, and is present in the semi-finished product PS in an amount of, for example, 16%, 18%, 20%, 22%, 24%, 26%, or 28%.

[0072] Together with the mixture M, the resin is contained in an amount of 20% to 70% by weight, preferably 30% to 60% by weight, and even more preferably 35% to 50% by weight based on the total weight of the semi-finished product PS, and is present in the semi-finished product PS in an amount of, for example, 38%, 40%, 42%, or 45%.

[0073] In addition to the mixture M and the resin, the semi-finished product PS preferably further contains (i) water in an amount of 5% to 30% by weight, preferably 10% to 20% by weight based on the total weight of the semi-finished product PS, for example, 15%; and (ii) additives, preservatives, and glycols, such as propylene glycol or diethylene glycol, etc., in an amount of 0.5% to 5% by weight, preferably 1% to 1.5% by weight based on the total weight of the semi-finished product PS, for example, 2%.

[0074] In addition to the mixture M and the resin, the semi-finished product PS may preferably further contain a preservative, for example, a mixture of two preservatives, 5-chloro-2-methyl-2H-isothiazol-3-one [EC number 247-500-7] and 2-methyl-2H-isothiazol-3-one [EC number 220-239-6], at a weight ratio of 3:1, with Index number: 613-167-00-5 and CAS: 55965-849.

[0075] The preferred embodiments of the semi-finished product PS of the present invention are reported in Table 1.

[0076]

Table 1

[0077] The resin is selected from the group consisting of, or consisting of, polyurethanes, urethanes, polyacrylics, acrylics, polyvinyls, vinyls, polyamides, or amides known to those skilled in the art.

[0078] The finished product PF, which includes the semi-finished product PS, is the object of the present invention.

[0079] The semi-finished product PS contained in the finished product PF is present in an amount of 0.1% to 10% by weight, preferably 0.5% to 8% by weight, and even more preferably 1% to 6% by weight, based on the weight of the paint product, for example, in amounts of 1%, 2%, 3%, 4%, or 5%.

[0080] In one embodiment, the paint product may preferably be present in the finished product PF together with the semi-finished product PS, in the form of a liquid, dispersion, or aqueous dispersion.

[0081] In one embodiment, the paint product is preferably a varnish, enamel, or paint or waterborne paint; preferably selected from the group consisting of, or consisting of, said varnish, enamel, or paint for outdoor or indoor surfaces, and is preferably selected from waterborne or organic solvent-based paints. For example, the waterborne paint may be used on outdoor or indoor surfaces.

[0082] In one embodiment, the waterborne paint product is preferably selected from compatible one-component or two-component products for indoor or outdoor surfaces made of stone wall, linoleum, or wood, for spray, brush, or roller-type application.

[0083] In another embodiment, the organic solvent-based paint product is preferably a two-component product of acrylic and / or methacrylic and / or urethane and / or polyurethane-based for indoor or outdoor surfaces, such as glass, aluminum, steel, plastic, polymer, linoleum, cloth, natural leather, synthetic leather, wood, natural cloth, artificial cloth, or synthetic cloth, for spray or roller or brush-type application.

[0084] The finished product PF of the present invention may be regarded as a fluid solution having a polymer matrix and a solute (dextro usnic acid and / or its salt, such as sodium salt, etc.). Considering the above, examples of paint products include water-based and solvent-based paints, varnishes, and enamels. Varnishes produce, for example, transparent films. Further, considering that paints, varnishes, and enamels have many applications, the most commonly and widely used raw materials in the fields of industrial varnishes, paints, and enamels, such as solvents, polymer matrices (resins), additives, and pigments / fillers, are reported below. For example, a solution can be cited as an example of a transparent varnish, while if undissolved components are dispersed, this applies to a dispersion.

[0085] List of solvents most commonly used in the preparation of varnishes (transparent), enamels (colored), and paints (for building products): water, butyl alcohol, isopropyl alcohol, ethyl acetate, n-butyl acetate, isobutyl acetate, toluene, xylene, naphtha solvents, mineral spirits, acetone, methyl ethyl ketone, methyl isobutyl ketone, butyl glycol, dibutyl glycol, glycol ethers, methoxypropyl acetate.

[0086] List of the most common polymer matrices: Resins are usually found in solvent solutions or aqueous emulsions. The polymer matrix is dissolved in solvents and in emulsions / dispersions in water in which they are insoluble. For example, synthetic or vegetable oils, vegetable fatty acids, castor oil, saturated or unsaturated fatty acids.

[0087] So far, we have looked at the categories of components that make up varnishes (forming a somewhat glossy transparent film on the manufactured product), but for paints (resin polymer powder) and enamels (rich in resin), pigments, fillers, and dyes must be added in certain cases. In that case, there are functional components. Fillers characterize paints and backgrounds, pigment enamels. For example, fillers include calcium carbonate, mica, talc, barium sulfate, quartz; functional pigments such as zinc phosphate, iron oxide, etc.; anticorrosive pigments: pasty aluminum; pigments: titanium dioxide, iron oxide, organic pigments yellow, orange, red, green, blue, magenta violet; effect pigments (optical interference).

[0088] In one embodiment, for example, a finished product PF for application on natural or synthetic leather, or animal hides, may be added to a base (coating product) having the following composition: (i) water in an amount of 75% to 85% by weight, preferably 78% to 80%; (ii) SiO2 in an amount of 1% to 8% by weight, preferably 2% to 5%; (iii) di(propylene glycol) methyl ether in an amount of 0.5% to 5% by weight, preferably 1% to 2%; (iv) siloxane and silicone in an amount of 2% to 5% by weight, preferably 2.5% to 3.5%; and (v) a polymer in an amount of 10% to 20% by weight, preferably 16% to 18%. In this case, a crosslinking agent for crosslinking to obtain a film having properties such as withstanding wear tests, for example, Taber tests, friction against alcohol and gasoline, etc., can also be used. Regarding a cloth, for example, a non-woven fabric (NWF) made of polypropylene or polyester, a solution (finished product) containing 100 parts by weight of deionized water, 0.6 parts by weight of racemic usnic acid, or the dextrorotatory type D(+), and 0.9 parts by weight of beta-cyclodextrin may be used.

[0089] In another embodiment, for example, the finished product PF for application to walls or ceilings and surfaces (horizontal and vertical) made of concrete or gypsum board, linoleum, or wood has, for example, the following composition: (i) an amount contained in an amount of 60% to 80% by weight, preferably 70%, for example 72% by weight, of resin (as part of the paint product); (ii) an amount contained in an amount of 2% to 10% by weight, preferably 3.5% to 8% by weight, for example 6.5% by weight, of inert additive; (iii) an amount contained in an amount of 10% to 30% by weight, preferably 15% to 25% by weight, for example 17% by weight, of water; (iv) an amount contained in an amount of 0.5% to 5% by weight, preferably 1% to 3% by weight, for example 2% by weight, of di(propylene glycol) methyl ether; (v) an amount contained in an amount of 1% to 4% by weight, preferably 1.5% to 3% by weight, for example 2.5% by weight, of diethylene glycol may be added to a base (paint product - opaque, transparent, and two-component water finish background). This base is for application on surfaces made of, for example, wood or marquetry, and also on outdoor surfaces. This base has excellent surface hardness, abrasion resistance, chemical resistance, and UV resistance. To further enhance its chemical resistance, for example, a catalyst may be added in an amount contained in an amount of 70% to 90% by weight, preferably 80% by weight, of polyisocyanate resin, and 10% to 30% by weight, preferably 20% by weight, of propylene carbonate, based on the total weight of the catalyst, for example, in an amount contained in an amount of 3% to 15% by weight, preferably 10% by weight, based on the total weight of the finished product PF. This finished product PF may be applied using spray, roller, or brush techniques.

[0090] In another embodiment, the finished product PF for application to, for example, glass, aluminum, or steel may have, for example, the following composition: (i) an acrylic resin in an amount of 60% to 85% by weight, preferably 70% to 80% by weight, for example 75% by weight; (ii) xylene in an amount of 10% to 30% by weight, preferably 15% to 25% by weight, for example 20% by weight; (iii) an additive in an amount of 0.5% to 4% by weight, preferably 1% to 3% by weight, for example 2% by weight, added to a base (a two-component transparent glossy acrylic paint product). This base can provide a highly durable coating with high light resistance and is thus suitable for outdoor and indoor applications. To further enhance the chemical resistance of the finished product PF, when applied on glass, for example, an aliphatic polyisocyanate resin in an amount of 30% to 50% by weight, preferably 35% to 45% by weight, for example 40% by weight, based on the total weight of the formulation; xylene in an amount of 20% to 40% by weight, preferably 25% to 35% by weight, for example 30% by weight; methyl ethyl ketone in an amount of 20% to 40% by weight, preferably 25% to 35% by weight, for example 30% by weight, and a catalyst in an amount of 1% to 10% by weight, preferably 3% to 5% by weight, based on the total weight of the finished product PF may be added. This finished product PF may be applied using spray technology.

[0091] Preferred embodiments FPn of the present invention are reported below.

[0092] FP1. An inclusion compound (ci) comprising, or consisting of, (i) D-ursolic acid as a natural origin, as an enantiomer, or a salt thereof, or a mixture thereof, and (ii) beta-cyclodextrin.

[0093] The inclusion compound (ci) as described in FP1, wherein FP2. D - usnic acid, or a salt thereof, or a mixture thereof (i), and beta - cyclodextrin (ii), preferably (2 - hydroxypropyl)-β - cyclodextrin, are contained in a weight ratio of 3:1 to 1:3, preferably 2:1 to 1:2, more preferably 1.5:1 to 1:1.5, and even more preferably 1:1.

[0094] FP3. D - usnic acid, or a salt thereof, or a mixture thereof (i) is extracted from lichens, preferably from the group consisting of or including the genera Parmelia, Cladonia, Usnea, Physcia, Caloplaca, Umbilicaria, Lecanora, Ramalina and combinations thereof, or from the group consisting of these, more preferably from the genus Parmelia, and even more preferably from Parmelia sulcata. The cyclodextrin (ii) contains or consists of beta - cyclodextrin, preferably (2 - hydroxypropyl)-β - cyclodextrin, and (i) and (ii) are in a ratio of 1:1. The inclusion compound (ci) as described in FP1 or FP2.

[0095] FP4. The inclusion compound (ci) contains solid particles of D - usnic acid, or a salt thereof, or a mixture thereof (i) as a pure enantiomer, and the solid particles have an average particle distribution contained in 0.01μm to 50μm, preferably 0.1μm to 30μm, more preferably 0.15μm to 20μm, and even more preferably 0.2μm to 15μm. The inclusion compound (ci) as described in any one of FP1 to FP3.

[0096] FP5. Use of the inclusion compound (ci) according to any one of FP1 to FP4 as an antibacterial or bacteriostatic agent against both Gram-negative bacteria and Gram-positive bacteria, wherein the bacteria are preferably selected from the group consisting of Escherichia coli, Klebsiella, Acinetobacter baumannii, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus, Enterococcus species, vancomycin-resistant Enterococcus (VRE), Actinobacteria, Actinobacteria species, Clostridium difficile, and combinations thereof, or consisting of the foregoing.

[0097] FP6. The use according to FP5, wherein the inclusion compound (ci) is added during the process of preparing a manufactured product in the form of a film or layer made of plastic, resin or thermoplastic polymer, polyethylene (PE), polyvinyl chloride (PVC), polyethylene terephthalate (PET), latex; or the inclusion compound (ci) is spread or disposed on the surface of the manufactured product in an amount of 0.1% to 20% based on the weight of the manufactured product.

[0098] FP7. (a) The inclusion compound (ci) according to any one of claims 1 to 4; (b) an acrylic resin, a polyurethane resin, an acrylic-polyurethane resin, or a mixture thereof; (c) optionally a pigment or an opacifier; (d) water and comprising or consisting of a liquid composition.

[0099] FP8. (a) an amount of the inclusion compound (ci) contained in an amount of 0.1% to 15% by weight, preferably 0.2% to 10% by weight, more preferably 0.3% to 7% by weight based on the total weight of the liquid composition; (b) the acrylic resin, the polyurethane resin, the acrylic-polyurethane resin, or a mixture thereof contained in an amount of 1% to 80% by weight, preferably 2% to 75% by weight, more preferably 5% to 70% by weight based on the total weight of the liquid composition; (c) Optionally, an amount of the pigment or the opacifier contained in an amount of 10% to 40%, preferably 15% to 35% by weight, more preferably 20% to 30% by weight, based on the total weight of the liquid composition; (d) Water contained in an amount of 1% to 40%, preferably 2% to 30% by weight, more preferably 3% to 22% by weight, based on the total weight of the liquid composition The liquid composition according to FP7, comprising or consisting of these.

[0100] FP9. Preferably as a coating or paint for stone walls, or for walls and floors, for example for linoleum floors, more preferably as an antibacterial architectural coating or as a bacteriostatic agent for both Gram-positive bacteria and Gram-negative bacteria, the use of the liquid composition according to any one of FP7 to FP8.

[0101] FP10. Use of beta-cyclodextrin, preferably (2-hydroxypropyl)-β-cyclodextrin, as a selective complexing agent for (i) pure enantiomers of D-usnic acid, or salts thereof, or mixtures thereof, from a racemic mixture (or racemate) of naturally occurring usnic acid.

[0102] The present invention reports some examples of the present invention, shown by non-limiting examples, below. ISO 22196 is incorporated to measure the antibacterial activity of the mixture M, semi-finished product PS, and finished product PF according to Table 1, applied on the plastic surface.

[0103] Advantageously, the mixture M, the semi-finished product PS, and the finished product PF meet the requirements of the following standards UNI EN ISO 7784:2016 (abrasion resistance) and UNI EN ISO 18593:2018.

[0104] Advantageously, the mixture M, the semi-finished product PS, and the finished product PF do not require a photoactive agent or external energy such as ultraviolet light or light of any wavelength, because they can be fixed alone when applied on the surface. Experimental Part A

Example

[0105] [Example 1] Test on the effectiveness of the aqueous liquid composition of the present invention against the Gram-positive pathogen Staphylococcus aureus (MRSA) In accordance with the test method ISO 22196:2007, the aqueous liquid composition was tested for effectiveness against the Gram-positive pathogen Staphylococcus aureus. The aqueous liquid composition contains D-usnic acid inclusion compound as a pure enantiomer of natural origin and (2-hydroxypropyl)-β-cyclodextrin.

[0106] The types of materials to be tested were 6 untreated samples (divided into 2 groups) and 6 treated samples (divided into 2 groups), and the compositions according to the present invention were divided as follows: - Reference (time 0 hour): CTRL1, CTRL2, CTRL3; - Reference (time 24 hours): CTRL4, CTRL5, CTRL6; - Samples treated with the composition according to the present invention: SSC7, SSC8, SSC9; Samples treated with the composition according to the present invention with the aging method applied: SSC10, SSC11, SSC12.

[0107] The samples to be analyzed included 50×50 mm square plastic supports coated with the material to be tested, which were treated by painting. A square polyethylene coating film, 40×40 mm and 0.1 mm thick, was used. The bacterial strain to be tested was methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300 (10 6 cells / ml), and the bacterial inoculum volume was 0.4 ml. The change added to the international standard procedure was that the volume of the neutralizing agent (SCDLP) = 20 ml.

[0108] The test is considered to be valid as it meets the following conditions as described in the ISO 22196:2007 standard: 1) (LOG MAX -LOGMIN ) / LOG MEAN ≤0.2 2) The average number of viable bacteria immediately after inoculation of the untreated test (reference) is 6.2×10 3 cells / cm 2 ~2.5×10 4 cells / cm 2 within the range; 3) The number of viable bacteria in each control sample after 24-hour culture is 6.2×10 1 cells / cm 2 or more.

[0109] The following formula: R=(U T -U0)-(A T -U0)=U T -A T is used to calculate the bacterial activity R.

[0110] [Table 2]

[0111] The bacterial activity R is shown in the attached Figure 3. [Example 2]

[0112] Effectiveness test of the aqueous liquid composition according to Example 1 for Gram-negative pathogen Escherichia coli Following the same procedure as in Example 1, but in this case the bacterial strain to be tested is the Gram-negative pathogen strain Escherichia coli ATCC 8739 (6×10 5 cells / ml).

[0113] The bacterial activity R is calculated according to the following formula: R=(U T -U0)-(A T -U0)=U T -A T as follows.

[0114] [Table 3]

[0115] The bacterial activity R is shown in the attached Figure 4.

[0116] The above-mentioned Examples 1 and 2 showed a reduction in bacterial viability of approximately 100% (R% > 99.99%) after exactly 24 hours of contact, and the results were calculated according to the logarithmic efficacy index of the antibacterial material as per the guidelines.

[0117] This reduction was seen in both types of tested microorganisms (R 大腸菌) log = 4.96; R 黄色ブドウ球菌 log = 4.30) with very close values, and advantageously showed effective antibacterial properties against both Gram-positive and Gram-negative pathogenic bacteria.

[0118] From this consideration, it should be noted that the composition which is the subject of the present invention may be useful for many purposes, including the environment of daily life and environments in fields such as business, home, medical - hospital. [Example 3]

[0119] Effectiveness test of the aqueous liquid composition according to Example 1 in non - specific representation of the level of bacterial contamination The laboratory results obtained from surface tests, which are suitable for showing in non - specific representation the level of bacterial contamination at the sampling sites, are summarized below.

[0120] In the first series of tests conducted in a hospital facility, a room used as a dental clinic, where the aqueous liquid composition of Example 1 which is the subject of the present invention was pre - applied to the surface to make the surface resistant to bacterial contamination, was designated.

[0121] In the second series of tests conducted in a kindergarten, the aqueous liquid composition of Example 1 which is the subject of the present invention was applied on the walkable surfaces of the floors of the rooms (shared area and rest room) to make the surfaces resistant to bacterial contamination.

[0122] To obtain the traceability of the results obtained above, the standard of UNI EN ISO 18593:2018 "Horizontal surface sampling method" using a contact medium was adopted. Specifically, "Contact slide 2 Liofilchem" was used. Tests were also conducted on the walls and surfaces to determine the level of bacterial contamination representative of the natural background (starting conditions) before applying the aqueous liquid composition of Example 1, which is the subject of the present invention, to the walls and walkable surfaces.

[0123] Activities were carried out under normal conditions of use in a room of a dental clinic (hospital facility) or a room used for child care (kindergarten). Therefore, the research of the present invention was conducted in a situation where bacterial populations actually exist, and in some cases, even in the presence of clinic users. These conditions support the tendency for walkable surfaces to withstand recontamination if the recontamination is punctate and not distributed over the entire surface.

[0124] In addition to personal protective equipment (gowns, gloves, and masks), the material used for the bacterial load test is the Liofilchem contact medium for specific applications, product code 525272, in accordance with the described standard. The use of the commercial product allows for the direct use of the surface of the contact medium in contact with the walls or walkable surfaces of the room, subsequent incubation in a thermostat for a fixed period of 24 hours at 30 °C, and the reading of the results expressed in colony-forming units (CFU) / cm 2 to enable.

[0125] In the tests in the hospital facility, the agreed procedure allows for the identification of four separate points on each of the four walls in the treatment room and the identification of those points from 1 to 4 in a counterclockwise direction according to the logic of the distribution of the surface to be sampled, which is as typical as possible. Therefore, each sample should be considered to correspond to 10 cm in terms of surface area. Therefore, in each sampling session, there are 4 locations per wall, a surface area consisting of 16 samples, for a total of 160 cm 2 corresponding. 2Analysis was performed. As shown by the attached photograph of Figure 5, starting from the right wall of the entrance door of the room, the positions of the four walls were numbered from 1 to 4 up to the wall in front of the armchair with a small window, the wall with the window, and finally the wall on the left side of the entrance door.

[0126] In the implementation of sample collection in a hospital facility, in accordance with the logic of the distribution of the points to be detected, the largest surface area was covered during the four sample collection sessions. Table 2 below summarizes the results of the separate sample collections in the hospital facility for each sampling date.

[0127]

Table 4

[0128] In the tests in the kindergarten, the agreed procedure enables the identification of a series of points distributed over the walkable surfaces of the rooms used, in accordance with the logic of the distribution of the surfaces to be sampled that are as typical as possible. Thus, each sample should be considered to correspond to 10 cm in terms of surface area. 2 should be considered to correspond to.

[0129] The test samples from the two areas present in the kindergarten are summarized in Table 3 (shared area) and Table 4 (rest room) below.

[0130]

Table 5

[0131]

Table 6

[0132] In conclusion, considering the starting values, and in some cases also the types of colonies that are still punctiform and separated, and taking into account the initial values and the reduction of the microbial load on the surfaces treated with the composition that is the subject of the present invention, the data collected during the sample collection sessions show the overall resistance of the surfaces to recontamination: - As can be observed from the chart shown in FIG. 6, the tests conducted in hospital facilities reached 90%, just under 3000 CFU / cm 2 to values approaching 300 CFU / cm 2 . Another important piece of data worth noting is the numerical constant of 468.75 CFU / cm 2 , 468.75 CFU / cm 2 , 405.0 CFU / cm 2 , 312.5 CFU / cm 2 (obtained with a certain tendency for the number of microorganisms to decrease over time). - In the tests conducted in kindergartens, as can be observed from Tables 3 and 4 mentioned above, the bacterial load remains at 8% - 12%. [Example 4]

[0133] Further efficacy tests of the aqueous liquid composition according to Example 1 in terms of non - specific expressions of the level of bacterial contamination The tests were carried out in accordance with ISO 18593 and showed excellent repeatability accuracy.

[0134] The sampling conditions were as follows: Collection for reference: Inpatient / consulting room at rest after sanitation; Collection after treatment: Inpatient / consulting room during use.

[0135] Such conditions represent the worst - case scenario for verifying the effectiveness of the treatment with the composition that is the subject of the present invention.

[0136] After obtaining a series of excellent in - vitro results (ISO 22196 and ASTM 2180), the treatment is proposed as a candidate for preventing and controlling the bacterial load on hospital surfaces.

[0137] For in - vivo verification before and after said treatment, bacterial load samples were collected by "Contact slide ISO 18593" to monitor the trend of the overall load expressed in CFU / m 2 (colony - forming units per square meter).

[0138] After approximately 25 days, other samples were collected to monitor the expression of effectiveness over time.

[0139] Laboratory tests by accelerated aging showed excellent stability of effectiveness over time (effectiveness guaranteed for 3 years).

[0140] The number of samples collected ensures that the statistical data obtained is very good (maximum 32 tests per room per process).

[0141] This verification considers five different hospital environments that can be classified as clinics and inpatient rooms.

[0142] The tests were conducted according to the latest guidelines for microbiological monitoring of hospital environments.

[0143] The attached Figures 7, 8, 9, and 10 show the results separated by room and sampling date, as well as their trends over time. Furthermore, Table 5 below reports the percentage of reduction / decrease in bacterial load for each figure.

[0144]

Table 7

[0145] Advantageously, the surface treated with the aqueous liquid composition of Example 1, which is the subject of the present invention, is always sanitized thanks to the inclusion compound (ci) contained therein.

[0146] Advantageously, such effectiveness of sanitization (reduction of pathogen load), as measured by tests after accelerated aging according to ISO 22196:2007(E) (the version effective at the priority date of the patent application of the present invention), is constant for at least 3 years from application.

[0147] Advantageously, the aqueous liquid composition which is the subject of the present invention (such as that of Example 1 etc.) is particularly used in a hospital environment if the composition is deemed suitable for restricting the in-hospital bacterial load (and not only that) with respect to both Gram-positive pathogenic bacteria and Gram-negative bacteria. This unexpected result advantageously enables the patient to stay in as sterile an environment as possible. Experimental part B [Example 1]

[0148] 1.1 Objectives Verify the bactericidal effectiveness of a device treated with an antibacterial agent which is the subject of the present invention, based on naturally derived usnic acid and / or its related salts, preferably the sodium salt, which is in racemic form or the dextrorotatory form D(+). The test was carried out according to the procedure described and the standard reference ASTM E2180-07, using microbial strains regarded as indicators.

[0149] 2.1 Principle of the test method The ASTM E2180-07 standard describes a test method for quantitatively evaluating the antibacterial effectiveness of an agent incorporated into a polymer surface or a hydrophobic surface. This method requires inoculating a standard culture of microbial cells into a dissolved semi-solid agar (agar slurry). A thin layer of the inoculated agar slurry is transferred onto the surface to be tested and onto other surfaces used as controls. After one or a plurality of specified contact times, the surviving microorganisms are recovered by eluting the agar slurry inoculum from the test substrate in a neutralizing agent and extracted using a method to ensure complete removal of the inoculum from the test surface. Serial dilutions are then prepared and each is seeded for incorporation into an appropriate growth medium. After incubating the plates under the conditions specified for the test microorganism used, the number of colonies of surviving microorganisms for each dilution is counted and recorded. The percent reduction of microorganisms is then calculated by comparing the surviving microorganisms on a sample of the surface treated with the antibacterial agent with those recovered on an untreated surface taken as a reference.

[0150] 3.1. Reference law The tests described in this report refer to the laws specified below. ASTM E2180-07, "Standard Test Method for Determining the Activity of Incorporated Antimicrobial Agent(s) in Polymeric or Hydrophobic Materials".

[0151] 3.2. Internal References The tests conducted and described below refer to the following operating procedures and instructions in accordance with the quality management system certified by ISO 9001 and ISO 13485. - P08 "Analysis and Verification Tests", 5th Edition, 01 / 10 / 2013; - P09 "Infrastructure Management", 3rd Edition, 01 / 10 / 2013; - P10 "Equipment Management", 3rd Edition, 01 / 10 / 2013; - I01 "Strain Management", 1st Edition, 10 / 05 / 2011; - I02 "Management of Growth Media and Reagents", 3rd Edition, 02 / 03 / 2015.

[0152] 4. Identification of Samples to be Tested The product to be tested consists of a device treated with a mixture M based on racemic or dextrorotatory D(+)-form of naturally derived usnic acid and / or its related salts, preferably sodium salt, to obtain antibacterial properties; a device of the same material without an antibacterial agent was used as a reference. Samples of devices treated or untreated with the antibacterial agent used in the trial, as identified below, were manufactured according to internal procedures. The sample to be tested was made into a rectangle with dimensions corresponding to 2×8 cm.

[0153]

Table 8

[0154] 5. Equipment and Reagents The following laboratory reagents, materials, and equipment were used in the tests: - Diluent for the preparation of microbial suspensions: physiological saline containing 9 g / l NaCl, COD.SA279 / 2015, expiration date 10 / 03 / 2016; - Bacterial growth medium: Tryptone Soya Agar (TSA), Cod.SA289 / 2015, expiration date 22 / 03 / 2016; - Agar slurry: semi-gelatinous preparation containing 3 g / l agar and 8.5 g / l NaCl, Cod.SA292 / 2015, expiration date 24 / 12 / 2015; - Recovery culture solution / neutralizer: solution in Tryptone Soya broth containing 30 ml / l Tween 80, 30 g / l saponin, 1 g / l L-histidine, 3 g / l egg lecithin, and 5 g / l sodium thiosulfate, Cod.SA230 / 2015, expiration date 14 / 01 / 2016; - Thermostatic bath, MPM INSTRUMENTS, Cod.SA65, controlled at (45 ± 1) °C; - Thermostatic bath, CHIMICA OMNIA, Cod.SA15, controlled at (45 ± 1) °C; - Vortex mixer, VELP SCIENTIFICA, Cod.SA52; - Thermostat, PID SYSTEM, Cod.SA66, controlled at (36 ± 1) °C; - Refrigerated thermostat, VELP SCIENTIFICA, Cod.SA82, controlled at (31 ± 1) °C; - Spectrophotometer, GENESYS 10, Cod.SA26; - Various sterile materials (e.g., scissors, forceps, etc.).

[0155] The media and reagents used will be prepared according to the manufacturer's instructions and / or the methods of reference as reported in the internal operating instructions. The media used in the tests were checked for fertility and sterility. The equipment was managed according to the internal procedures, and at the time of the tests, the equipment was in valid calibration conditions.

[0156] Work environment preparation, material control, and handling operations will be performed in accordance with specifications laid down in relevant internal procedures.

[0157] 6. Methodology Description 6.1.Experimental Conditions Antibacterial efficacy testing was carried out under the following experimental conditions. - Microbial strain: Escherichia coli ATCC 10536 (Gram-negative bacterium).

[0158] The culture conditions employed for the test strains are detailed in the table below.

[0159] [Table 9]

[0160] Contact Time: Specify the contact time agreed with the customer in the table below.

[0161] [Table 10] - Reference; device not treated with mixture M (containing no usnic acid).

[0162] 6.2. Test Description The microbial strains were plated on a slant of appropriate medium for 24 hours, and then the number of bacteria was estimated by spectrophotometric measurements to be 1–5 × 10 8 The cells were diluted in saline until a concentration of 10 cfu / ml was reached. -6 The number of microbial cells in the suspension was determined using a 10 scalar dilution in saline up to 100%. Two 1 ml aliquots were taken from this dilution and plated for incorporation into the medium. After incubation and counting of the colonies grown on the plates, the number of colony forming units per ml (cfu / ml) in the suspension was determined.

[0163] 1.0 ml of the microbial suspension was inoculated onto 100 ml of agar slurry and maintained in a lysed state at a temperature of 45°C to obtain a concentration of 1–5 × 10 6The final concentration of cells in each agar slurry contained between cfu / ml was obtained. Test and reference devices were prepared by inserting five small pieces into appropriately identified plates during the contact time defined above. 1.0 ml of the inoculated agar slurry was transferred to each of the test and control samples prepared for the test suspension. Inoculation was performed at an angle and speed that avoided the suspension spilling outside the sample. After gelling the agar slurry inoculum, the samples were placed in an incubator at a temperature suitable for the growth of the microbial strain for the defined contact time. To prevent the agar slurry inoculum from drying, a tray filled with water was used to maintain the humidity in the thermostat at a level exceeding 75%. At each of the defined contact times, the samples of the treated and non-reference devices were removed from the Petri dishes and transferred to flasks containing a neutralizing broth in a volume such that a 1:10 dilution of the original inoculum was obtained. The flasks were sonicated for 1 minute and then mechanical mixing using a vortex was performed to ensure complete detachment of the agar slurry from the samples. Subsequently, serial 1:10 dilutions were made in the neutralizing broth and each was seeded by incorporation into an appropriate medium. Samples were seeded by incorporation into a lysis medium to determine the effectiveness of detachment from the treated surface. After culturing, the number of colonies grown for each of the prepared dilutions was counted and recorded, and the number of viable microorganisms (cfu / ml) was calculated for each contact time.

[0164] 6.3. Calculation and Presentation of Results As defined in the reference standard, the results were expressed as the percentage reduction in microbial contamination of the treated device sample relative to the untreated one. The geometric mean of the number of microorganisms recovered in five replicates performed on the device treated with the antimicrobial agent and the untreated device was calculated. Thus, the percentage difference between the antilogarithm of the geometric mean of the control samples and the antilogarithm of the geometric mean of the treated samples was calculated. Geometric mean = (LogR1 + LogR2 + LogR3 + LogR4 + LogR5) / 5 Where R1 / 2 / 3 / 4 / 5 = the total number of microorganisms recovered after exposure and culturing of the substance or control under test (replicates 1 / 2 / 3 / 4 / 5). Reduction rate (percentage) = (a - b) × 100 / a In the formula, a = Mantissa of the geometric mean of the untreated reference device b = Mantissa of the geometric mean of the treated device

[0165] 6.4. Criteria for test validity If the initial microbial recovery is 10 4 cfu / ml or more, the test is considered valid. To declare the effectiveness of the device under the test conditions, the ASTM 2180 reference standard requires that the reduction rate of microbial contamination evaluated with respect to the untreated reference be 99% or more.

[0166] 7. Results The obtained results are summarized in the following table.

[0167]

Table 11

[0168]

Table 12

[0169]

Table 13

[0170]

Table 14

[0171] 8. Conclusions Based on the obtained results, in accordance with the criteria for test validity and in accordance with the requirements of the ASTM E-2180-07 standard (reduction exceeding 99%) - The device treated with the mixture M based on usnic acid identified as "Sample 1" (synthetic-derived usnic acid, not of the present invention) is effective against the test strain (E. coli) at a contact time of 72 hours; - Devices treated with a mixture based on usnic acid, identified as "Sample 2" (naturally derived usnic acid according to the present invention), are effective against the test strain (E. coli) at a contact time of 24 hours. It can be concluded that [Example 2]

[0172] 2.1. Purpose The bactericidal effectiveness of devices treated with mixture M, based on racemic or dextrorotatory D(+) naturally derived usnic acid and / or its related salts, preferably sodium salts, was verified. Using a microbial strain considered as an indicator, the tests were carried out according to the procedures described and the standard reference ASTM E2180-07.

[0173] 2.2. Principle of the test method The ASTM E2180-07 standard describes a test method for quantitatively evaluating the antibacterial effectiveness of agents incorporated into polymer or hydrophobic surfaces. This method requires inoculating a standard culture of microbial cells into a dissolved semi-solid agar (agar slurry). A thin layer of the inoculated agar slurry is transferred onto the surface to be tested and onto other surfaces used as controls. After one or more specified contact times, the surviving microorganisms are recovered by eluting the agar slurry inoculum from the test substrate in a neutralizing agent and extracted using a method to ensure complete removal of the inoculum from the test surface. Serial dilutions are then prepared and each is seeded for incorporation into an appropriate growth medium. After incubating the plates under the conditions specified for the test microorganism used, the number of colonies of surviving microorganisms for each dilution is counted and recorded. The percent reduction of microorganisms is then calculated by comparing the number of surviving microorganisms on samples of the surface treated with the antibacterial agent with those recovered on an untreated surface taken as a reference.

[0174] 3.1. Reference laws The tests described in this report refer to the laws specified below. - ASTM E2180-07 "Standard Test Method for Determining the Activity of Incorporated Antimicrobial Agent(s) in Polymeric or Hydrophobic Materials".

[0175] 3.2. Internal References The tests conducted and described in this report refer to the following operating procedures and instructions that comply with the quality management systems certified by ISO 9001 and ISO 13485. - P08 "Analysis and Verification Tests", 5th Edition, 01 / 10 / 2013; - P09 "Infrastructure Management", 3rd Edition, 01 / 10 / 2013; - P10 "Equipment Management", 3rd Edition, 01 / 10 / 2013; - I01 "Strain Management", 1st Edition, 10 / 05 / 2011; - I02 "Management of Growth Media and Reagents", 3rd Edition, 02 / 03 / 2015.

[0176] 4. Identification of Samples to be Tested The product to be tested consists of devices treated with a usnic acid-based mixture M to obtain antibacterial properties; devices of the same material without antibacterial agents were used as references. Samples of devices treated or untreated with the antibacterial agent used in the trial, as identified below, were manufactured according to internal procedures.

[0177] The sample to be tested was made into a rectangle with dimensions corresponding to 2×8 cm.

[0178]

Table 15

[0179] 5. Equipment and Reagents The following laboratory reagents, materials, and equipment were used in the tests: - Diluent for preparing microbial suspension: physiological saline containing 9 g / l NaCl, COD.SA226 / 2015, expiration date 10 / 01 / 2016; - Bacterial growth medium: Tryptone Soya Agar medium (TSA), Cod.SA225 / 2015, expiration date 10 / 01 / 2016; - Yeast growth medium: Sabouraud Agar medium (SAB), Cod.SA219 / 2015, expiration date 10 / 01 / 2016; - Agar slurry: semi-gelatinous preparation containing 3 g / l agar and 8.5 g / l NaCl, Cod.SA229 / 2015, expiration date 14 / 10 / 2015; - Recovery culture solution / neutralizer: solution in Tryptone Soya culture solution containing 30 ml / l tween 80, 30 g / l saponin, 1 g / l L-histidine, 3 g / l egg lecithin, 5 g / l sodium thiosulfate, Cod.SA230 / 2015, expiration date 14 / 01 / 2016; - Thermostat, MPM INSTRUMENTS, Cod.SA65, controlled at (45 ± 1) °C; - Thermostat, CHIMICA OMNIA, Cod.SA15, controlled at (45 ± 1) °C; - Vortex mixer, VELP SCIENTIFICA, Cod.SA52; - Thermostat PID SYSTEM, Cod.SA66, controlled at (36 ± 1) °C; - Refrigerated thermostat, VELP SCIENTIFICA, Cod.SA82, controlled at (31 ± 1) °C; - Spectrophotometer, GENESYS 10, Cod.SA26; - Various sterile materials (e.g., scissors, forceps, etc.).

[0180] The media and reagents used will be prepared according to the manufacturer's instructions and / or the methods of reference as reported in the internal operation instructions of the environmental research. The media used in the tests were checked for fertility and sterility.

[0181] 6. Description of the method 6.1. Experimental Conditions The antibacterial efficacy test was conducted under the following experimental conditions. - Microbial strains: Staphylococcus aureus MRSA ATCC 43300 (Gram-positive bacterium), Escherichia coli ATCC 10536 (Gram-negative bacterium), Candida albicans ATCC 10231 (yeast).

[0182] The culture conditions adopted for the test strains are described in detail in the following table.

[0183] [Table 16]

[0184] Contact time: The contact time is specified in the following table.

[0185] [Table 17]

[0186] 6.2. Description of the Test The microbial strains were transplanted onto the slant of an appropriate medium for 24 hours and then diluted with physiological saline until reaching a concentration of 1 - 5×10 8 cfu / ml as estimated by the measured values of spectrophotometry. Ten scalar dilutions in physiological saline up to 10 -6 were used to determine the number of microbial cells in each suspension. Two 1-ml aliquots were taken from this dilution and seeded for incorporation into the medium. After culturing and counting the colonies grown on the plates, the number of colony-forming units per ml (cfu / ml) in each suspension was determined. 1.0 ml of each microbial suspension was seeded into 100 ml of agar slurry, maintained in a dissolved state at a temperature of 45°C, and 1 - 5×10 6The final concentration of cells in each agar slurry contained between cfu / ml was obtained. Test and reference devices were prepared by inserting five small pieces into appropriately identified plates during the contact time defined above. 1.0 ml of the inoculated agar slurry was transferred to each of the test and control samples prepared for each of the test suspensions. Inoculation was carried out at an angle and speed such as to avoid the suspension spilling outside the sample. After gelling the agar slurry inoculum, the samples were placed in an incubator at a temperature suitable for the growth of the microbial strain for the defined contact time. To prevent the agar slurry inoculum from drying out, a tray filled with water was used to maintain the humidity in the thermostat at a level exceeding 75%. At each of the defined contact times, the samples of the treated and non-reference devices were removed from the Petri dishes and transferred to flasks containing a neutralizing culture medium in a volume such that a 1:10 dilution of the original inoculum was obtained. The flasks were subjected to ultrasonic treatment for 1 minute, followed by mechanical mixing using a vortex to ensure complete detachment of the agar slurry from the samples. Thus, serial 1:10 dilutions were made in the neutralizing culture medium and each was seeded by incorporation into a medium suitable for the growth of the specific microbial strain. Samples were seeded by incorporation into a lysis medium to determine the effectiveness of detachment from the treated surface. After incubation, the number of colonies grown for each of the prepared dilutions was counted and recorded, and the number of viable microorganisms (cfu / ml) was calculated for each suspension and contact time.

[0187] 6.3. Calculation and Presentation of Results As defined in the reference standard, the results were expressed as the percentage reduction in microbial contamination of the treated device samples relative to the untreated ones. The geometric mean of the number of microorganisms recovered in five replicates performed on the devices treated with the antimicrobial agent and the untreated devices was calculated. The percentage difference between the logarithm of the geometric mean of the control samples and the logarithm of the geometric mean of the treated samples was calculated. Geometric mean = (LogR1 + LogR2 + LogR3 + LogR4 + LogR5) / 5 Wherein, R1 / 2 / 3 / 4 / 5 = Total number of microorganisms recovered after exposure to the test substance or control and culturing (replicates 1 / 2 / 3 / 4 / 5). Reduction rate (percentage) = (a - b) × 100 / a Wherein, a = True number of geometric mean of the untreated reference device b = True number of geometric mean of the treated device

[0188] 6.4. Criteria for test validity If the initial recovery of microorganisms is 104 cfu / ml or more, the test is considered valid. To declare the effectiveness of the device under the test conditions, the ASTM 2180 reference standard requires that the reduction rate of microbial contamination evaluated with respect to the untreated reference be 99% or more.

[0189] 7. Results The obtained results are summarized in the following table.

[0190]

Table 18

[0191]

Table 19

[0192]

Table 20

[0193]

Table 21

[0194] 8. Conclusions Based on the results obtained, in accordance with the criteria for test validity and according to the requirements defined by ASTM E-2180-07 standard (reduction exceeding 99%), it can be concluded that the device treated with usnic acid (the subject of the present invention) is effective against a representative strain of Gram-positive bacteria (Staphylococcus aureus MRSA) under the test conditions at a contact time of 24 hours.

Claims

1. A mixture M comprising (a) naturally occurring usnic acid and / or (b) a related salt thereof, or consisting of the same.

2. The naturally occurring usnic acid of (a) is a combination or association C / A of naturally occurring dextrorotatory D(+)-usnic acid and naturally occurring levorotatory L(-)-usnic acid; preferably, the dextrorotatory form D(+) is contained in an amount of 0.1% to 99.9% by weight based on the total weight of the combination or association C / A, and / or the levorotatory form L(-) is contained in an amount of 99.9% to 0.1% by weight based on the total weight of the combination or association. The mixture M according to Claim 1.

3. The naturally occurring usnic acid of (a) is a racemate of 50% (+) and 50% (-), or is the dextrorotatory form D(+). The mixture M according to Claim 1 or 2.

4. The salt of the naturally occurring usnic acid of (b) is a salt of an alkali metal or an alkaline earth metal; preferably, the salt of the naturally occurring usnic acid is sodium usnate. The mixture M according to any one of Claims 1 to 3.

5. The salt of the naturally occurring usnic acid of (b) is a racemate or the dextrorotatory form D(+); preferably, the salt is present in an amount of dextrorotatory form D(+) of 0.1% to 99.9% by weight based on the total weight of the combination or association C / A, and / or in an amount of levorotatory form L(-) of 99.9% to 0.1% by weight based on the total weight of the combination or association C / A. The mixture M according to any one of Claims 1 to 4.

6. The naturally occurring usnic acid of (a) and the related salt of (b) are present in amounts of 1:10 to 10:1 by weight, preferably 1:5 to 5:1 by weight, and even more preferably 1:3 to 3:1 by weight, for example, in an amount of 1:1, based on the total weight of the mixture M. The mixture M according to any one of Claims 1 to 5.

7. Usnic acid is preferably of the formula: (+)-usnic acid 2,6-diacetyl-7,9-dihydroxy-8,9-dimethyldibenzofuran-1,3(2H,9bH)-dione; (+)-usnic acid derived from the genus Usnea; CAS: 7562-61-0, EC: 231-456-0; preferably sodium usnate is of the formula: 2,6-diacetyl-7,9-dihydroxy-8,9b-dimethyldibenzofuran-1,3(2H,9bH)-dione monosodium salt; CAS: 34769-44-3, EC: 252-204-6; preferably the purity of the said (a) usnic acid and / or the said (b) usnate is included in 95% to 99.9%, preferably 96% to 99.5%, even more preferably 97% to 98%, for example 98%, the mixture M according to any one of claims 1 to 6.

8. The said mixture M can be in a solid or semi-solid state, in a dispersed or suspended form, in the form of a gel, or in a liquid state; preferably the said mixture M can be in the form of flakes, granules, powders, pellets, or can be in an aqueous solution or a hydroalcoholic solution, or in an organic solvent, the mixture M according to any one of claims 1 to 7.

9. The said (a) naturally derived usnic acid and / or the said (b) its related salt is a solid powder having an average particle size included in 1 micron to 100 microns, preferably 5 microns to 50 microns, even more preferably 10 microns to 20 microns, the mixture M according to any one of claims 1 to 8.

10. Use of the mixture M according to any one of claims 1 to 9, wherein the said mixture M is preferably used as having antibacterial, antibacterial growth-promoting, bacteriostatic, bactericidal, antifungal, anti-yeast (e.g., Candida), antifungal, or anti-filamentous fungal (e.g., Saccharomycetes) properties against Gram-positive bacteria and / or Gram-negative bacteria, such as those having the scientific names of the genus Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia.

11. A method for making the surface antibacterial, antibacterial growth-promoting, bacteriostatic, bactericidal, anti-mold, anti-yeast (e.g., Candida genus), anti-fungal, or anti-filamentous fungal (e.g., Saccharomycetes class) against preferably Gram-positive and / or Gram-negative bacteria, such as those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia, and the like, which realizes the application of the mixture M to the surface according to any one of claims 1 to 9 by spray, roller, or brush techniques.

12. A semi-finished product PS containing the mixture M according to any one of claims 1 to 9 and a resin.

13. The semi-finished product PS according to claim 12, which is in the form of a semi-solid cream or paste.

14. The semi-finished product PS according to claim 12 or 13, wherein the resin is selected from the group consisting of, or consisting of, polyurethane, urethane, polyacrylic, acrylic, polyvinyl, vinyl, polyamide, or amide polymers or resins.

15. The mixture M contained in the semi-finished product PS contains, or consists of, the (a) usnic acid of natural origin and / or the (b) related salts thereof, and preferably the mixture M is contained in an amount of 20% to 80% by weight, preferably 35% to 65% by weight, and even more preferably 40% to 50% by weight based on the total weight of the semi-finished product PS, for example, in an amount of 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, or 49%, and is present in the semi-finished product PS. The semi-finished product PS according to any one of claims 12 to 14.

16. The resin, together with the mixture M, is contained in an amount of 20% to 70% by weight, preferably 30% to 60% by weight, and even more preferably 35% to 50% by weight based on the total weight of the semi-finished product PS, for example, in an amount of 38%, 40%, 42%, or 45%, and is present in the semi-finished product PS. The semi-finished product PS according to any one of claims 12 to 15.

17. In addition to the mixture M and the resin, the semi-finished product PS preferably contains (i) water in an amount of 5% to 30% by weight, preferably 10% to 20% by weight, for example 15% by weight, based on the total weight of the semi-finished product PS; and (ii) additives, preservatives, and glycols such as propylene glycol or diethylene glycol in an amount of 0.5% to 5% by weight, preferably 1% to 1.5% by weight, for example 2% by weight, based on the total weight of the semi-finished product PS. The semi-finished product PS according to any one of claims 12 to 16 may further contain such substances.

18. In addition to the mixture M and the resin, the semi-finished product PS may contain a preservative, for example, a mixture of 5-chloro-2-methyl-2H-isothiazol-3-one [EC number 247-500-7] and 2-methyl-2H-isothiazol-3-one [EC number 220-239-6], Index number: 613-167-00-5 and CAS: 55965-84-9, as a mixture of two preservatives in a weight ratio of 3:

1. The semi-finished product PS according to any one of claims 12 to 17 may contain such substances.

19. Use of the semi-finished product PS according to any one of claims 12 to 18, wherein the semi-finished product PS is preferably used as having antibacterial, antibacterial growth-inhibiting, bacteriostatic, bactericidal, antifungal, anti-yeast (e.g., Candida genus), antifungal, or anti-filamentous fungal (e.g., Saccharomycetes class) properties against Gram-positive and / or Gram-negative bacteria, for example, those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli.

20. A method for making the surface antibacterial, antibacterial growth-inhibiting, bacteriostatic, bactericidal, antifungal, anti-yeast (e.g., Candida genus), antifungal, or anti-filamentous fungal (e.g., Saccharomycetes class) against Gram-positive and / or Gram-negative bacteria, for example, those having the scientific names of the genera Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli. The method realizes the application of the semi-finished product PS according to any one of claims 12 to 18 to the surface by spray, roller, or brush techniques.

21. A finished product PF comprising the semi-finished product PS according to any one of claims 12 to 18 and a paint product.

22. The finished product PF according to claim 21, wherein the paint product is selected from water-based or organic solvent-based varnishes, enamels, or paints.

23. The semi-finished product PS is included in an amount of 0.1% to 10% by weight; preferably 0.5% to 8% by weight; even more preferably 1% to 6% by weight, relative to the weight of the paint product, and is present in an amount such as 1%, 2%, 3%, 4%, or 5% by weight, of the finished product PF according to claim 21 or 22.

24. The paint product may preferably be in the form of a liquid, dispersion, or aqueous dispersion, of the finished product PF according to any one of claims 21 to 23.

25. The paint product may preferably be selected from the group consisting of or consisting of varnishes, enamels, or paints; preferably the varnish, enamel, or paint is preferably selected from those of a water solvent system or an organic solvent system, of the finished product PF according to any one of claims 21 to 24.

26. The finished product PF is applied on a horizontal or vertical surface, such as a floor, wall, or ceiling made of cement, lime board or gypsum board, linoleum, or polyvinyl chloride (PVC), polyamide (PA), polyethylene (PE), polyester (PES) or polyethylene terephthalate (PTF), and preferably the surface is present in a clinic, emergency department, hospital, dental clinic, sports field, kindergarten, school, or in, for example, a public or private facility, or in, for example, a supermarket and shopping mall, or in a sports field, in washroom and toilet facilities, of the finished product PF according to any one of claims 21 to 25.

27. Preferably, it is applied on an indoor or outdoor surface made of, for example, wood, steel, aluminum, cloth, non-woven fabric, animal skin, leather, or glass; preferably, it is applied on the surface by spray, roller, or brush technology, of the finished product PF according to any one of claims 21 to 26.

28. Use of the finished product PF according to any one of claims 21 to 27, wherein the finished product PF is preferably used as having antibacterial, antibacterial growth-inhibiting, bacteriostatic, bactericidal, anti-mold, anti-yeast (e.g., Candida genus), anti-fungal, or anti-filamentous fungal (e.g., Saccharomycetes class) properties against Gram-positive and / or Gram-negative bacteria, such as those having the scientific names of the genus Klebsiella, Enterobacteriaceae, genus Enterobacter, genus Pseudomonas, and genus Escherichia.

29. A method for making the surface antibacterial, antibacterial growth - inhibitory, bacteriostatic, bactericidal, anti - mold, anti - yeast (e.g., Candida genus), antifungal, or anti - filamentous fungal (e.g., Saccharomycetes class) against preferably Gram - positive and / or Gram - negative bacteria, such as those having the scientific names of the genus Klebsiella, Enterobacteriaceae, Enterobacter, Pseudomonas, and Escherichia coli, etc., which realizes the application of the finished product PF according to any one of claims 21 to 27 to the surface by spray, roller, or brush techniques.

30. An inclusion compound (ci) comprising, or consisting of, (i) naturally - derived D - usnic acid as an enantiomer, or a salt thereof, or a mixture thereof, and (ii) beta - cyclodextrin.

31. The inclusion compound (ci) according to claim 30, wherein D - usnic acid, or a salt thereof, or a mixture thereof (i), and beta - cyclodextrin (ii), preferably (2 - hydroxypropyl) - β - cyclodextrin, are present in the inclusion compound (ci) in a weight ratio of 3:1 to 1:3, preferably 2:1 to 1:2, more preferably 1.5:1 to 1:1.5, and even more preferably 1:

1.

32. The inclusion compound (ci) according to claim 30 or 31, wherein D - usnic acid, or a salt thereof, or a mixture thereof (i) is extracted from lichens, preferably from the group consisting of or comprising the genus Usnea, Cladonia, Lecanora, Parmelia, Physcia, Umbilicaria, Ramalina, and combinations thereof, more preferably from the genus Usnea, and even more preferably from Usnea longissima, the cyclodextrin (ii) comprises or consists of beta - cyclodextrin, preferably (2 - hydroxypropyl) - β - cyclodextrin, and (i) and (ii) are in a ratio of 1:

1.

33. The inclusion compound (ci) contains D-ursolic acid as a pure enantiomer, or a salt thereof, or a mixture thereof, and the solid particles are contained in the range of 0.01 μm to 50 μm, preferably in the range of 0.1 μm to 30 μm, more preferably in the range of 0.15 μm to 20 μm, and even more preferably in the range of 0.2 μm to 15 μm, and has an average particle distribution. The inclusion compound (ci) according to any one of claims 30 to 32.

34. Use of the inclusion compound (ci) according to any one of claims 30 to 33 as an antibacterial or bacteriostatic agent against both Gram-negative bacteria and Gram-positive bacteria, wherein the bacteria are preferably Escherichia coli, Klebsiella, Acinetobacter baumannii, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus, Enterococcus species, Vancomycin-resistant Enterococcus (VRE), Actinobacteria, Actinobacteria species, Clostridium difficile, and combinations thereof, or a group consisting of them.

35. The inclusion compound (ci) is added in the process of preparing a product in the form of a plastic film or layer, a thermoplastic resin or polymer, polyethylene (PE), polyvinyl chloride (PVC), polyethylene terephthalate (PET), latex; or the inclusion compound (ci) is spread or arranged on the surface of the manufactured product in an amount of 0.1% to 20% based on the weight of the product. Use according to any one of claims 30 to 34.

36. (a) The inclusion compound (ci) according to any one of claims 30 to 33; (b) An acrylic resin, a polyurethane resin, an acrylic-polyurethane resin, or a mixture thereof; (c) Optionally a pigment or an opacifier; (d) Water A liquid composition comprising or consisting of them.

37. (a) The inclusion compound (ci) in an amount of 0.1% to 15% by weight, preferably 0.2% to 10% by weight, and even more preferably 0.3% to 7% by weight based on the total weight of the liquid composition; (b) the acrylic resin, the polyurethane resin, the acrylic-polyurethane resin, or a mixture thereof, in an amount of 1% to 80% by weight, preferably 2% to 75% by weight, more preferably 5% to 70% by weight, based on the total weight of the liquid composition; (c) optionally, the pigment or the opacifier, in an amount of 10% to 40%, preferably 15% to 35% by weight, more preferably 20% to 30% by weight, based on the total weight of the liquid composition; (d) water, in an amount of 1% to 40%, preferably 2% to 30% by weight, more preferably 3% to 22% by weight, based on the total weight of the liquid composition The liquid composition according to claim 36, comprising or consisting of the above.

38. Use of the liquid composition according to claim 36 or 37 as an architectural paint or coating, preferably as a coating or paint for stone walls, or as a coating or paint for walls and floors, for example for linoleum floors, more preferably as an antibacterial architectural coating or as a bacteriostatic agent against Gram-positive bacteria and Gram-negative bacteria.

39. Use of beta-cyclodextrin, preferably (2-hydroxypropyl)-β-cyclodextrin, as a selective complexing agent for D-usnic acid, or a salt thereof, or a mixture (i) thereof, as a pure enantiomer from a racemic mixture (or racemate) of naturally occurring usnic acid.

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