Liquid composition for influencing microbiota on subject's skin comprising chitosan

Abstract

To provide a liquid cosmetic composition comprising chitosan and having beneficial properties for topical application to the skin, and to provide uses of the liquid cosmetic composition.SOLUTION: The present invention relates to liquid compositions as well as the use of liquid compositions for differentially promoting the growth of the microbiome. The liquid composition forms a membrane of the invention when applied to the skin of a subject. The liquid composition as well as the membrane comprise chitosan or a salt thereof with a degree of acetylation of 20% or less and at least one further agent. The present invention further relates to pharmaceutical compositions for the treatment of dysbiosis.SELECTED DRAWING: None

Description

[Technical field]

[0001] The polysaccharide chitosan is an at least partially N-deacetylated derivative of chitin. Chitin can be widely found in arthropods, gels, exoskeletons of crustaceans and cuticles of insects. Chitin is usually derived from such natural sources. Generally, chitosan is produced synthetically by hydrolysis of chitin, but it can also be derived directly from nature, for example from certain fungi that produce it. The two polysaccharides are usually differentiated by the different solubilities of chitin and chitosan in dilute acids. The soluble form of chitosan can have a degree of acetylation (DA) between 0% and about 60%, the upper limit depending on parameters such as processing conditions, molecular weight and solvent properties. While soluble in acidic aqueous media, chitosan precipitates at pHs above 6.3.

[0002] Both chitin and chitosan are promising polymers for biomedical applications due to their biocompatibility, biodegradability, structural similarity to glycosaminoglycans, and lack of immunogenicity.

[0003] For example, WO2011 / 026498A1 discloses a tissue dressing material having deacetylated natural chitosan as the main component.

[0004] WO2011 / 026869A1 discloses a tissue dressing kit comprising a tissue dressing having deacetylated natural chitosan for use in contact with a patient's tissue, and a stripping solvent for removing the tissue dressing from the tissue.

[0005] Furthermore, chitosan is also known to be useful as a cosmetic agent, for example for dental care, hair care, skin care and oral care (for a comprehensive summary see review by Aranaz et al., "Cosmetics and Cosmeceutical Applications of Chitin, Chitosan and Their derivatives", Polymers 2018, 10, 213). For example, chitosan derivatives have been described as antimicrobial agents, moisturizers, antioxidants, skin conditioners, cleansers, emollients and skin protectants. Furthermore, chitosan, in the form of encapsulated nanoparticles, has been used as a vehicle for active ingredients in skin care.

[0006] Chitosan is included in these cosmetics in various ways. For example, chitosan may be dissolved in liquid or chitosan may be used without dissolving. When used in dissolved form on the skin, chitosan may or may not precipitate and forms a film covering the skin, depending on various factors such as the pH of the liquid cosmetic formulation or the amount of chitosan and / or the presence of further cosmetic agents. As already mentioned above, chitosan usually precipitates at a pH above 6.3, which is highly dependent on the skin's integrity and surface condition. However, the normal pH of the skin is between pH 4.0 and 6.0 (Gruber 2016, "Behandlungsstrategien bei stagnierenden Wunden", pp. 1-42). A precipitated film of chitosan having a pH of 6.3 is not ideal for skin care uses because skin is generally in better condition at pH values ​​below 5.0 (e.g., with respect to resident skin flora, biophysical parameters of barrier function, moisturization and scaling) than skin with a pH above 5.0 (see Lambers et al., "Natural skin surface pH is on average below 5, which is beneficial for its resident flora." Int J Cosmet Sci. 2006 Oct;28(5):359-70).

[0007] The biological integrity of the skin, as the largest human organ, is of high importance. In case of severe burns or damage, medical treatment is necessary to restore skin integrity and to support natural repair mechanisms. However, not only such severe conditions require care. Small, localized disorders of the skin, which may not necessarily be due to pathological conditions, also require care. These disorders may be caused, for example, by mechanical stressors; temperature stress; radiation stress; external factors such as oxygen, carbon dioxide, metal ions, chemicals, water or nutrients, or by the fluctuation, exchange or mediation of internal factors or combinations thereof. Such disorders may also be caused, for example, by an imbalance in the skin microflora or microbiome. Furthermore, disorders may be caused by skin peeling, laser treatments, plasma treatments, tattoos and tattoo removal.

[0008] Such disorders may not directly cause medical symptoms such as serious lesions or wounds requiring immediate medical treatment, but may be accompanied by surface pain, for example, stressed nails, itching, burn wet skin areas, smell, rough cracky fissures, dryness, areas of ugliness, etc.

[0009] A cosmetic membrane, preferably with barely visible persistence, that supports the care of such an unbalanced skin surface, while at the same time reducing or preventing the above symptoms or the deterioration of severe skin lesions, would be of great value in cosmetic applications. Also, a cosmetic membrane that can function as a stable support for conventional make-up without hindering optical impact would be of great value. Furthermore, a liquid composition with chitosan that promotes or re-establishes a healthy microbiome would be extremely useful in cosmetic and pharmaceutical applications. Summary of the Invention [Problem to be solved by the invention]

[0010] The object of the present invention is to provide a further chitosan-based cosmetic preparation having beneficial properties for topical use on the skin.A further object of the present invention is to provide a chitosan-based product for topical use on the skin that beneficially influences the skin microbiome and / or supports the formation of a healthy microbiome on the skin.A still further object of the present invention is to provide a chitosan-based pharmaceutical composition that re-establishes or promotes a healthy microbiome. [Means for solving the problem]

[0011] The above objectives can be achieved by the liquid composition and its use as defined herein. The above objectives are also achieved by a film formed by topically applying the liquid composition to the skin of a subject and the use of such a film. Furthermore, the above objectives can be achieved by a pharmaceutical composition.

[0012] Thus, in a first aspect, the present invention relates to a liquid cosmetic composition comprising chitosan for use in the differential promotion of the growth of the microbiota of ectodermal tissue of a subject.

[0013] In one embodiment, the liquid cosmetic composition is applied topically to form a cosmetic film.

[0014] In another embodiment, the film formed has a thickness of 0.001 nm to 50 μm, preferably 0.001 nm to 10 μm, and more preferably 0.001 nm to 1 μm.

[0015] In another embodiment, the film-forming liquid cosmetic composition differentially promotes the growth of one or more microbial taxa relative to another microbial taxa (i.e., to a different degree).

[0016] In another embodiment, the film-forming liquid cosmetic composition promotes the growth of one or more beneficial microbial taxa over one or more pathogenic microbial taxa.

[0017] In another embodiment, the at least one beneficial taxon comprises Staphylococcus epidermidis, Staphylococcus mitis, Staphylococcus capitis, Corynebacterium specs., Propionibacterium acnes, Malassezia pachydermatis, Streptococcus spec., Streptococcus spec., Lactobacillus spec., Micrococcus spec., and Bacillus spec.

[0018] In another embodiment, the at least one pathogenic taxon comprises Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Enterococcus faecalis / faecium, E. coli, Klebsiella pneumoniae, Candida albicans, Microsporum canis, Acinetobacter baumanii, Staphylococcus intermedius, and Staphylococcus pseudointermedius.

[0019] In another embodiment, the chitosan has a degree of acetylation of 15% or less, more preferably 10% or less, even more preferably 5% or less, or even more preferably 2.5% or less.

[0020] In another embodiment, the liquid cosmetic composition comprises one additional cosmetic agent.

[0021] In another embodiment, the one additional cosmetic agent is selected from the group comprising urea, glycolic acid, glyoxylic acid, glycerol, pentylene glycol, lactic acid, ascorbic acid, pyroglutamic acid, citric acid, tartaric acid, fumaric acid, succinic acid, malic acid, mandelic acid, aloe vera, rosa gallica, hyaluronic acid, salicylic acid, gallic acid, cellulose and its derivatives, pectin and its derivatives, gum arabic, dextrin, cyclodextrin, xanthan gum, thiocyanates, amino acids, sorbic acid, sodium chloride, or combinations thereof.

[0022] In another embodiment, the at least one additional cosmetic agent comprises glycolic acid and lactic acid.

[0023] In another embodiment, the composition comprises, relative to the total weight of the liquid cosmetic composition: 0.01-4.0% (w / w) chitosan, 0.005 to 2.5% (w / w) glycolic acid, 0.005 to 2.5% (w / w) lactic acid, has.

[0024] In another embodiment, the liquid cosmetic composition comprises a disinfectant.

[0025] In another embodiment, the disinfectant comprises an alcohol, an aldehyde, iodine, chlorine, a quaternary ammonium compound, a peroxide, an amphoteric surfactant, a phenol, an alkylamine, an acid and / or a base.

[0026] In another embodiment, the ectodermal tissue is skin.

[0027] In another embodiment, the ectodermal tissue is the epidermis.

[0028] In another embodiment, the epidermis is damaged epidermis, the damage comprising sunburn, acne, cuts, abrasions, incisions, pimples, blisters, stings, burns, ageing, irritated skin, radiated skin, laser treated skin, plasma treated skin, tattoos, tattoo removal, skin peeling, scar tissue, dry skin, fatty skin, cracks, stretch marks, or wrinkles.

[0029] In another embodiment, the subject's ectodermal tissue, skin, epidermis or damaged epidermis has previously been sterilized or disinfected.

[0030] In another embodiment, the epidermis is a stressed epidermis, and the stress is due to prostheses, endoprostheses, orthoses, reinforced exoskeletons, plasters, compression bandages, stockings, bandages, latex protection, massagers, masks for ventilation, apnea prevention, work- or protective clothing, gloves, pacifiers, tight clothes or shoes, disinfectants, cosmetic treatments, cosmetics, preservatives, cleaning agents, sweat, lack of personal hygiene, lying or sitting for long periods of time, wound dressings, or the like. It can be caused by skin irritation, sunburn, burns, puncture wounds, radiation, laser treatment, plasma treatment, getting tattooed and / or removing tattoos.

[0031] In another embodiment, the stress is caused by a prosthesis, an endoprosthesis, a brace, a reinforced exoskeleton, a bandage, a pressure bandage, a stocking, a dressing, a latex protective material, a massager, a ventilation mask, work or protective clothing, gloves, a pacifier, tight clothing or shoes, lying or sitting for long periods of time, or a wound dressing.

[0032] In another embodiment, the subject's ectodermal tissue, skin, epidermis, damaged or stressed epidermis has previously been sterilized or disinfected.

[0033] In a second aspect, the present invention provides a method for producing a method for treating a cancer cell comprising the steps of: a) chitosan or a salt thereof, wherein the degree of acetylation of the chitosan is 20% or less; and b) at least one further cosmetic agent; A liquid cosmetic composition comprising: The liquid cosmetic composition has a pH of about 4.0 to about 6.5; and the at least one additional cosmetic agent comprises glycolic acid and lactic acid.

[0034] In one embodiment of the second aspect, the degree of acetylation of the chitosan is 15% or less, more preferably 10% or less, even more preferably 5% or less, or even more preferably 2.5% or less.

[0035] In another embodiment of the second aspect, the composition comprises, relative to the total weight of the liquid cosmetic composition: 0.010-4.0% (w / w) chitosan, 0.005 to 2.5% (w / w) glycolic acid, 0.005 to 2.5% (w / w) lactic acid, has.

[0036] In a third aspect, the present invention relates to a kit comprising a liquid cosmetic composition according to any of the previous aspects, further comprising a disinfectant, preferably selected from the group comprising an alcohol, an aldehyde, iodine, chlorine, a quaternary ammonium compound, a peroxide, an amphoteric surfactant, a phenol, an alkylamine, an acid and / or a base. [Brief description of the drawings]

[0037] [Figure 1] Change in pH of skin after treatment with a cosmetic composition having at least one additional cosmetic agent. This figure shows that the presence of a chitosan film significantly reduces the pH of cleansed skin having a pH above 6.0. [Diagram 2]Storage capacity of films formed from four cosmetic liquid compositions A to D (compositions A and B according to the present invention) containing cosmetic compositions with at least one additional cosmetic agent, evaluated at three different time points using the Skin PAMPA. [Diagram 3] Photograph showing results for test formulation E described in Example 3. [Figure 4] Photograph showing results for test formulation F described in Example 3. [Diagram 5] Photograph showing results for test formulation G described in Example 3. [Figure 6] Photographs showing results for test formulation E described in Example 4 after designated time points in the absence of contact with a surface or skin area. [Figure 7] Photographs showing results for test formulation E described in Example 4, with samples taken immediately after contact with the fabric and after 1 h incubation after contact. The fabric was contacted with normal skin. [Figure 8] Results of the test campaign regarding the suitability and / or recommendability of test formulation E for different indications (abrasions, pimples, cracks, insect bites, blisters, scar care and lip tingling). [Figure 9] Study investigator's evaluation of the effectiveness of Test Formulation E in treating or caring for abrasions, pimples, cracks, insect bites, blisters, scars, and for the treatment or care of stinging lips. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0038] Use of liquid cosmetic compositions with chitosan to differentially promote microbiome growth Surprisingly, it has been found that liquid cosmetic compositions with chitosan differentially promote the growth of healthy microbiome on skin.For example, the liquid cosmetic compositions with chitosan and the film formed by the liquid cosmetic compositions with chitosan promote the growth of one beneficial microbial taxonomic group over another less beneficial or even pathogenic microbial taxonomic group.This mechanism is useful in various skin care applications, as further listed below.This mechanism may be particularly advantageous for use after or simultaneously with disinfection frequently used on skin in cosmetic applications, such as tattoo applications or skin impurities, such as acne.

[0039] In a first aspect, the present invention relates to the use of a liquid cosmetic composition comprising chitosan for differentially promoting the growth of the microbiota of the ectodermal tissue of a subject.

[0040] In one embodiment, the liquid cosmetic composition comprising chitosan differentially promotes the growth of microbiota in ectodermal tissues of a subject.

[0041] In one embodiment, the liquid cosmetic composition with chitosan establishes and improves colonization of microbial taxa in ectodermal tissues of a subject. In another embodiment, the liquid cosmetic composition with chitosan modulates microbial taxa in ectodermal tissues of a subject. In a preferred embodiment, modulating microbial taxa includes increasing or decreasing the abundance of the taxa. In another preferred embodiment, modulating microbial taxa includes increasing or decreasing the abundance of the taxa relative to the abundance of the microbial taxa in the absence of the liquid composition. In another preferred embodiment, the liquid cosmetic composition with chitosan modulates microbial diversity in ectodermal tissues of a subject. In another preferred embodiment, the liquid cosmetic composition with chitosan modulates the function of the microbiota.

[0042] In another preferred embodiment, the liquid cosmetic composition differentially promotes the growth of one or more microbial taxa relative to another microbial taxa. In a more preferred embodiment, the liquid cosmetic composition promotes the growth of one or more beneficial microbial taxa relative to one or more pathogenic microbial taxa. In another more preferred embodiment, the liquid cosmetic composition promotes the growth of one or more beneficial microbial taxa while at the same time not harming said one or more pathogenic microbial taxa. In another more preferred embodiment, the liquid cosmetic composition promotes the growth of one or more beneficial microbial taxa while at the same time inhibiting the growth of said one or more pathogenic microbial taxa. In yet another preferred embodiment, the liquid cosmetic composition with chitosan does not harm the growth of one or more beneficial microbial taxa but inhibits the growth of one or more pathogenic microbial taxa.

[0043] The beneficial microbial taxa include Staphylococcus epidermidis, Staphylococcus mitis, Staphylococcus capitis, Corynebacterium specs., Propionibacterium acnes, Malassezia pachydermatis, Streptococcus spec., Streptococcus spec., Lactobacillus spec., Micrococcus spec. and Bacillus spec.

[0044] The pathogenic microbial taxa include Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Enterococcus faecalis / faecium, E. coli, Klebsiella pneumoniae, Candida albicans, Microsporum canis, Acinetobacter baumanii, Staphylococcus intermedius and Staphylococcus pseudointermedius.

[0045] In some cases, beneficial taxa can transform into pathogenic taxa. This can occur depending on their abundance, i.e. when they occur in increased abundance compared to the healthy state of the microbiome. In this embodiment, said pathogenic taxa can further include Propionibacterium, Steptrococcus spec. (e.g. in the case of acne) or Propionibacterium, Corynebacterium, Staphylococcus spec., Streptococcus spec., in particular Staphylococcus aureus and Staphylococcus epidermidis (e.g. in the case of psoriasis).

[0046] Liquid Compositions Comprising Chitosan In a second aspect, the present invention relates to a liquid composition comprising chitosan which is a cosmetic or pharmaceutical composition depending on its application. In this respect, the liquid composition can be used for the above and below mentioned cosmetic applications, including pharmaceutical applications such as for example the treatment of dysbiosis.

[0047] In one embodiment, the liquid composition comprises one additional agent.

[0048] In another embodiment, the at least one additional agent is selected from a COSMOS certified cosmetic component selected from the list provided at the following link: http: / / www.cosmos-standard-rm.org / verifmp.php, which is incorporated herein by reference.

[0049] In a preferred embodiment, the at least one additional agent is selected from the group comprising urea, glycolic acid, glyoxylic acid, glycerol, pentylene glycol, lactic acid, ascorbic acid, pyroglutamic acid, citric acid, tartaric acid, fumaric acid, succinic acid, malic acid, mandelic acid, aloe vera, rosa gallica, hyaluronic acid, salicylic acid, gallic acid, cellulose and its derivatives, pectin and its derivatives, gum arabic, dextrin, cyclodextrin, xanthan gum, thiocyanates, amino acids, sorbic acid, sodium chloride or combinations thereof.

[0050] In preferred embodiments, the dextrin is corn, tapioca, rice, potato, wheat or sorghum dextrine.

[0051] In a preferred embodiment, the cellulose or derivative thereof is a hydroxyethyl cellulose or a hydroxymethyl cellulose, such as Natrosol®.

[0052] In a preferred embodiment, the cyclodextrin is acetyl, dimaltosyl, hydroxyethyl, maltosyl or methyl cyclodextrin.

[0053] In another preferred embodiment, the cyclodextrin is an alpha, beta, or gamma cyclodextrin.

[0054] In a preferred embodiment, the at least one additional agent is an alpha hydroxyl carboxylic acid having from 2 to 6 carbon atoms.

[0055] In another preferred embodiment, the liquid composition is prepared under a protection gas to prevent oxidation and the product is packaged in a primary package that prevents oxygen from entering the primary package.

[0056] In another preferred embodiment, the liquid composition is produced under a protective gas to prevent oxidation and the product is packed in a primary packaging that blocks the ingress of oxygen into the primary packaging and blocks the ingress of air into said packaging to replace the used volume (airless dispensing principle).

[0057] In another preferred embodiment, the liquid composition is filled into the primary package using the airless dispensing principle.

[0058] In yet another preferred embodiment, the at least one additional agent is selected from the group consisting of pentylene glycol, glycolic acid, glycerol, urea, thiocyanate, or lactic acid, or combinations thereof.

[0059] In yet another preferred embodiment, the at least one additional agent is selected from the group consisting of glycolic acid, pentylene glycol, glycerol, urea, lactic acid, or combinations thereof.

[0060] In another preferred embodiment, the at least one additional agent is selected from the group consisting of glycolic acid, glycerol, and lactic acid, or a combination thereof.

[0061] In another preferred embodiment, the at least one additional agent is selected from the group consisting of glycolic acid, pentylene glycol, and lactic acid, or a combination thereof.

[0062] In another preferred embodiment, the at least one additional agent is selected from the group consisting of glycolic acid, urea, and lactic acid, or a combination thereof.

[0063] In a particularly preferred embodiment, the at least one additional agent comprises glycolic acid.

[0064] In a particularly preferred embodiment, the at least one additional agent comprises lactic acid.

[0065] In a particularly preferred embodiment, the at least one additional agent comprises glycolic acid and lactic acid.

[0066] In another particularly preferred embodiment, the at least one additional agent comprises glycolic acid, lactic acid, pentylene glycol, urea, and glycerol.

[0067] In another embodiment, the liquid composition comprises a pharmaceutical agent.

[0068] In another embodiment, the liquid composition comprises particles.

[0069] In another embodiment, the liquid composition comprises fibers.

[0070] In another embodiment, the liquid composition comprises vesicles.

[0071] In another preferred embodiment, the molar ratio of chitosan monomer to the acid or acid groups of the alpha hydroxyl carboxylic acid having 2 to 6 carbon atoms is between 1:1 and 1:1.1.

[0072] In another embodiment, the composition comprises a water / glycerol mixture, preferably a water / glycerol mixture containing more than 20% (w / w) glycerol as a solvent.

[0073] In another embodiment, the composition comprises a water / ethylene glycol mixture, preferably a water / ethylene glycol mixture containing more than 20% (w / w) ethylene glycol as a solvent.

[0074] In another embodiment, the composition comprises a water / ethylene glycol mixture, preferably a water / ethylene glycol mixture containing more than 20% (w / w) ethylene glycol as a solvent.

[0075] In another embodiment, the composition comprises a water / polyethylene glycol mixture, preferably a water / polyethylene glycol mixture containing more than 10% (w / w) polyethylene glycol as a solvent.

[0076] In another embodiment, the composition comprises a water / polypropylene glycol mixture, preferably a water / polypropylene glycol mixture containing more than 10% (w / w) polypropylene glycol as a solvent.

[0077] In another embodiment, the composition comprises a water / ethanol mixture, preferably a water / ethanol mixture containing more than 20% (w / w) ethanol as a solvent.

[0078] In another embodiment, the composition comprises a water / propanol mixture, preferably a water / propanol mixture containing more than 20% (w / w) propanol as a solvent.

[0079] In another embodiment, the composition comprises a water / isopropanol mixture, preferably a water / isopropanol mixture containing more than 20% (w / w) isopropanol as a solvent.

[0080] In another preferred embodiment, the liquid composition further comprises an emulsifier, a surfactant, or a wetting agent. The emulsifier, surfactant, or wetting agent helps the composition to be distributed evenly on the skin so that a thin, uniform (cosmetic) film is formed. The emulsifier, surfactant, and wetting agent are well known in the art. In a preferred embodiment, the emulsifier, surfactant, or wetting agent is selected from the group consisting of polysorbates, alkylamidobetaines, and alcohol polyglucosides, or combinations thereof. In a particularly preferred embodiment, the wetting agent is a polysorbate, more preferably Polysorbate 20.

[0081] In a preferred embodiment, the liquid composition further comprises a humectant, which keeps the skin moist and thus improves the condition of dry skin or rashes.

[0082] Examples of suitable humectants are: 1) water-soluble liquid polyols selected from the group consisting of glycerol, propylene glycol, hexylene glycol, butylene glycol, pentylene glycol, dipropylene glycol and mixtures thereof; 2) hyaluronic acid; 3) polyalkylene glycols of formula I: HO-(R"O) b -H, where R" is an alkylene group having from about 2 to about 4 carbon atoms, and b is an integer from about 1 to about 10; 4) Polyethylene glycol ether of methyl glucose of formula II: CH3-CH6H 10 O5-(OCH2CH2) c The preferred humectants include, but are not limited to, -OH, where c is an integer from about 5 to about 25; 5) urea; 6) fructose; 7) glucose; 8) honey; 9) lactic acid; 10) maltose; 11) sodium glucuronate; 12) pyroglutamic acid and its salts; 13) amino acids; 14) dexpanthenol; and 15) mixtures thereof. Pentylene glycol or glycerol are preferred humectants.

[0083] In another preferred embodiment, the degree of acetylation of the chitosan is 15% or less.

[0084] In another preferred embodiment, the degree of acetylation of the chitosan is 10% or less.

[0085] In yet another preferred embodiment, the degree of acetylation of chitosan is even more preferably 5% or less.

[0086] In a particularly preferred embodiment, the degree of acetylation of the chitosan is 2.5% or less.

[0087] In a particularly preferred embodiment, the degree of acetylation of the chitosan is 2.0% or less.

[0088] A lower degree of acetylation is adequate to mechanically protect the skin from harmful external stresses such as unwanted microorganisms colonizing the skin, while at the same time providing a suitable environment for skin care, and can limit or prevent the biodegradation or degradation of chitosan by lysozyme.

[0089] The degree of acetylation can be determined, for example, by Lavertu et al., "A validated 1 As disclosed in "H NMR method for the determination of the degree of deacetylation of chitosan," J. Pharm. Biomed. Anal. 2003, 32, 1149, 1 H NMR spectroscopy. In the present invention, "deacetylated native chitosan" refers to both native and deacetylated chitosan according to the above definition.

[0090] A preferred chitosan can be produced by a process having at least two deacetylation steps, the two deacetylation steps being separated by at least a washing step (and thus distinguished from a single deacetylation step), in which deacetylation by-products such as acetate are at least partially removed. Preferably, at least one, and more preferably all, deacetylation steps are hydrolysis steps. In the hydrolysis step, chitosan may be mixed with a solution of a hydroxide, such as sodium hydroxide. Preferably, in the hydrolysis step, chitosan is exposed to a temperature higher than room temperature, for example 100°C. Preferably, at the end of each deacetylation step, chitosan is washed, for example with water. Furthermore, at least at the end of the final deacetylation step, and preferably at the end of each deacetylation step, chitosan is dried.

[0091] In a particular embodiment of the present invention, an acetylation step is carried out between two deacetylation steps. In a preferred acetylation step, chitosan or an acidic chitosan solution may be mixed with an organic solvent and then treated with a carboxylic acid anhydride at room temperature. Preferably, at the end of the acetylation step, the acetylated chitosan is washed and dried.

[0092] In a preferred embodiment, the chitosan can be produced by a process having at least two deacetylation steps.

[0093] In a further preferred embodiment, the liquid composition is an aqueous solution, i.e. has water as a mixing medium or solvent, respectively. The chitosan is dissolved in an aqueous solution and forms a (cosmetic) film only after application of the cosmetic solution to the skin of the subject. In another preferred embodiment, the liquid cosmetic composition is applied topically to the skin in the form of an emulsion, dispersion, suspension, serum, gel, solution, sprayable liquid, aerosol or foam.

[0094] In a particularly preferred embodiment, the liquid cosmetic composition is applied topically to the skin in the form of a gel, which is applied in the form of a cosmetic film, which is then transformed into a (cosmetic) membrane by precipitation of chitosan and optionally by evaporation of the gel liquid.

[0095] In another preferred embodiment, the chitosan is natural chitosan. In another preferred embodiment, the chitosan or its salt is not a chitosan derivative such as chitosan argininamide.

[0096] Preferred salts of chitosan are those derived from the dissociation of chitosan, such as natural chitosan, in an inorganic acid, such as hydrochloric acid, or an organic acid selected from the group of monobasic or polybasic organic acids having 2 to 12 carbon atoms and a first pKa value between 1 and 5. Particularly preferred salts are the salts of citric acid, lactic acid, glycolic acid, glyoxylic acid, malic acid, succinic acid, fumaric acid, pyroglutamic acid, mandelic acid, oxalic acid, tartaric acid, salicylic acid and ascorbic acid. Particularly preferred salts are the salts of lactic acid and glycolic acid or combinations thereof.

[0097] The chitosan of the present invention is preferably a polymer of formula (I): [ka]

[0098] (In the formula, x and z are independently an integer of 5 to 25,000, y represents an integer from 1 to 25,000; R is an -NH2 group or an -NH3 + CH3CH(OH)C(O)O - or -NH3 + HOCH2C(O)O - where the sequence of units contained within the square brackets and having the indices x, y and z can be freely selected. Preferably, x and z each independently represent an integer from 5 to 20,000, preferably from 6 to 15,200, more preferably from 7 to 13,000. Also preferably, y is an integer from 1 to 25,000, preferably from 1 to 20,000, even more preferably from 1 to 15,000.

[0099] In another preferred embodiment, the liquid composition of the present invention has a viscosity of about 1 mPas to about 1000 mPas.

[0100] In yet another preferred embodiment, the liquid composition of the present invention has a viscosity of about 10 mPas to about 1000 mPas, preferably about 10 mPas to about 800 mPas. The viscosity of the composition may be determined, for example, using a glass capillary viscometer.

[0101] In another embodiment, the liquid composition is free of ethanol and / or isopropanol.

[0102] In yet another embodiment, the chitosan concentration of the liquid composition is at least 0.01% (w / w) relative to the total weight of the liquid composition. In another preferred embodiment, the chitosan concentration of the liquid composition is at least 0.1% (w / w) relative to the total weight of the liquid composition. In another preferred embodiment, the chitosan concentration of the liquid composition is at least 2.0% (w / w) relative to the total weight of the liquid composition.

[0103] In a further embodiment, the chitosan concentration of said liquid composition is less than or equal to 15% (w / w) relative to the total weight of said liquid composition.

[0104] In a further embodiment, the chitosan concentration of the liquid composition is less than or equal to 10% (w / w) relative to the total weight of the liquid composition.

[0105] In a further embodiment, the chitosan concentration of said liquid composition is less than or equal to 5% (w / w) relative to the total weight of said liquid composition.

[0106] In a further embodiment, the chitosan concentration of the liquid composition is less than or equal to 4% (w / w) relative to the total weight of the liquid composition.

[0107] In a further embodiment, the chitosan concentration of said liquid composition is less than or equal to 3% (w / w) relative to the total weight of said liquid composition.

[0108] In another preferred embodiment, the chitosan concentration in the liquid composition is 0.01% to 15% (w / w) based on the total weight of the liquid composition.

[0109] In a preferred embodiment, the chitosan concentration in the liquid composition is 0.01% to 10% (w / w) based on the total weight of the liquid composition.

[0110] In another preferred embodiment, the chitosan concentration in the liquid composition is 0.01% to 5% (w / w) based on the total weight of the liquid composition.

[0111] In a further preferred embodiment, the chitosan concentration of the liquid composition is from 0.1% to 4% (w / w) relative to the total weight of the liquid composition.

[0112] In another preferred embodiment, the chitosan concentration in the liquid composition is 2% to 4% (w / w) based on the total weight of the liquid composition.

[0113] In another preferred embodiment, the chitosan concentration in the liquid composition is 1% to 3% (w / w) based on the total weight of the liquid composition.

[0114] In a preferred embodiment, the concentration of glycolic acid in the liquid composition is 0.01% to 3% (w / w) based on the total weight of the liquid composition.

[0115] In a more preferred embodiment, the concentration of glycolic acid in the liquid composition is 0.1% to 1% (w / w) based on the total weight of the liquid composition.

[0116] In a preferred embodiment, the liquid composition has a lactic acid concentration of 0.01% to 3% (w / w) based on the total weight of the liquid composition.

[0117] In a more preferred embodiment, the lactic acid concentration of the liquid composition is 0.1% to 2% (w / w) based on the total weight of the liquid composition.

[0118] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 0.05% to 15% (w / w) chitosan, 0.0% to 9% (w / w) glycolic acid, and 0.0% to 9% (w / w) lactic acid, has.

[0119] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 0.1% to 15% (w / w) chitosan, 0.1% to 9% (w / w) glycolic acid, and 0.1% to 9% (w / w) lactic acid, has.

[0120] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 0.1% to 15% (w / w) chitosan, 0.1% to 3% (w / w) glycolic acid, and 0.1% to 3% (w / w) lactic acid, has.

[0121] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 0.20-4.0% (w / w) chitosan, 0.0-2.5% (w / w) glycolic acid, and 0.0-2.5% (w / w) lactic acid, has.

[0122] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 0.01% to 4% (w / w) chitosan, 0.1% to 2.0% (w / w) glycolic acid, and 0.1% to 2.2% (w / w) lactic acid, has.

[0123] In another embodiment, the composition comprises, relative to the total weight of the liquid cosmetic composition: 0.01-4.0% (w / w) chitosan, 0.005 to 2.5% (w / w) glycolic acid, 0.005 to 2.5% (w / w) lactic acid, has.

[0124] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 2.0-4.0% (w / w) chitosan, 0.3-2.2% (w / w) glycolic acid, and 0.3-2.2% (w / w) lactic acid, has.

[0125] In another embodiment, the composition comprises, relative to the total weight of the liquid cosmetic composition: 2.7-3.3% (w / w) chitosan, 0.7-1.3% (w / w) glycolic acid, 0.7-1.3% (w / w) lactic acid, has.

[0126] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 2.0-4.0% (w / w) chitosan, 0.3-2.2% (w / w) glycolic acid, and 0.3-2.2% (w / w) lactic acid, and the acetylation degree of chitosan is 15%.

[0127] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 2.0-4.0% (w / w) chitosan, 0.3-2.2% (w / w) glycolic acid, and 0.3-2.2% (w / w) lactic acid, and the acetylation degree of chitosan is 2%.

[0128] In an even more preferred embodiment, the liquid composition comprises, based on the total weight of the liquid composition: 0.20-4.0% (w / w) chitosan, 0.0-2.5% (w / w) glycolic acid, and 0.0-2.5% (w / w) lactic acid, and said composition is free of preservatives.

[0129] Relative to the total weight of the liquid composition, 0.20-4.0% (w / w) chitosan, 0.3-2.2% (w / w) glycolic acid, and 0.3-2.2% (w / w) lactic acid, and said composition is free of preservatives.

[0130] In another preferred embodiment, the liquid composition further comprises a preservative. It is particularly preferred that the preservative is sorbic acid in the free acid form or a cosmetically acceptable salt thereof. The sorbic acid or the cosmetically acceptable salt thereof is used at a concentration that is normally used as a preservative. It is more preferred that the liquid composition comprises sorbic acid at a concentration in the range of 0.02% to 0.2% (w / w) based on the total weight of the liquid composition. In another preferred embodiment, the preservative is potassium sorbate. In another preferred embodiment, the liquid composition does not comprise a preservative.

[0131] Colorants or pigments may be added to the liquid cosmetic composition to provide the desired color upon application to the skin. Such colorants or pigments are known and the concentrations required to obtain the desired color can be readily determined. The pigments may be inorganic or organic. Examples of inorganic pigments include iron oxides (red, black, brown), manganese violet, ultramarine (green, blue, pink, red or violet aluminum sulfosilicate), aquamarine, copper powder, mica, clays, silica and titanium dioxide. Organic pigments generally include various types such as azo, indigoid, triphenylmethane, anthraquinone and xanthine dyes, which are referred to as D&C and FD&C blues, browns, greens, oranges, reds, yellows, etc. Each of these pigments may further have a variety of different trade names or may exist as mixed compositions.

[0132] In certain embodiments, the liquid composition may contain a colorant or pigment in a concentration of 0%-30% (w / w), 1%-20% (w / w), 2%-15% (w / w), or 5%-15% (w / w).

[0133] The liquid cosmetic composition may contain fragrances or scavengers to provide a desired scent upon application to the skin. Such fragrances are known and the concentrations required to obtain a desired scent can be readily determined.

[0134] In certain embodiments, the liquid composition may contain the fragrance in a concentration of 0% to 5% (w / w), 0.001% to 1% (w / w), 0.001% to 0.5% (w / w) or 0.001% to 0.1% (w / w).

[0135] In certain embodiments, the liquid composition may contain an odor neutralizer at a concentration of 0% to 5% (w / w), 0.01% to 3% (w / w), 0.01% to 1% (w / w), or 0.01% to 0.5% (w / w).

[0136] In certain embodiments, the liquid composition may include an odor absorber in a concentration of 0% to 5% (w / w), 0.01% to 3% (w / w), 0.01% to 1% (w / w), or 0.01% to 0.5% (w / w).

[0137] In certain embodiments, the liquid composition can include sunblockers (organic chemicals, inorganic particulates, organic particulates with UV filtering properties).

[0138] A film formed by the liquid composition containing chitosan It usually takes a long time for drugs to be absorbed into the skin, or it is desirable for cosmetic or medical drugs to remain on the immediate surface of the skin. If these drugs are applied as creams or ointments and remain on the skin for a long time, the skin will have an oily sheen and a greasy, oily or sticky feel. On the other hand, if the same drugs are applied as gels or serums, they may be quickly absorbed into the deeper layers of the skin and cannot protect or care for the superficial layers of the skin.

[0139] Surprisingly, the liquid compositions of the present invention form a film that has the advantages of creams and ointments as well as gels and serums: the film on the skin is free or substantially free of oily sheen and does not cause the skin to feel greasy or sticky, in addition to allowing additional agents to remain on the skin surface.

[0140] In one embodiment, the liquid composition is applied topically to form a film. In one embodiment, the film formed has a thickness of 0.001 nm to 50 μm, preferably 0.001 nm to 10 μm, more preferably 0.001 nm to 1 μm. In a preferred embodiment, the film formed has a thickness of 0.001 nm to 50 μm, preferably 0.001 nm to 10 μm, more preferably 0.001 nm to 1 μm. In another preferred embodiment, the film formed has a thickness of 1 nm to 50 μm, preferably 1 nm to 10 μm, more preferably 1 nm to 1 μm. In another preferred embodiment, the film formed has a thickness of 10 nm to 10 μm, preferably 10 nm to 1 μm, more preferably 10 nm to 100 nm or 4 nm to 50 nm.

[0141] The film forms a stable support for conventional make-up applied subsequent to the formation of the film without interfering with the visual effect. The film may also allow for bidirectional transport of, for example, water, nutrients, oxygen, carbon dioxide and other gases, and may also function as a sustained release reservoir for other active molecules such as drugs, pharmaceutical compositions or vitamins.

[0142] When applied topically, the liquid composition comprising chitosan of the present invention forms a film, and therefore the same aspects as described for said liquid composition also apply to said film, which therefore has the same properties as those previously described for the liquid composition comprising chitosan, of influencing the microbiome of the ectodermal tissue of the subject.

[0143] It has also been found surprisingly that the film formed as a result of applying the liquid composition of the present invention can function as a stable support for conventional make-up without preventing visual effects.Following the formation of the film on the treated skin area, said area can be the subject of conventional make-up application.No visual unevenness occurs between the skin area covered with the film and untreated skin, or no visual effects occur along the border between covered and uncovered skin.

[0144] The chitosan or its salts are present in a precipitated form and are preferably the main component of the membrane. Additionally, the chitosan or its salts function as a carrier component of the membrane.

[0145] Surprisingly, when said liquid composition is applied to skin as described above, it is found that the resulting film has a pH of 3.5-6.5, which is particularly advantageous because the pH of film is close to that of skin.This means that the film covering the skin provides very good conditions for skin care, so that the skin is not further stressed by the application of said at least one further agent, for example when applied with a film of pH 7.

[0146] In a preferred embodiment, the pH of the membrane is about 4.0 to about 6.0. In another preferred embodiment, the pH of the membrane is about 4.0 to about 5.0. In another preferred embodiment, the pH of the membrane is about 4.5 to about 5.5. In another preferred embodiment, the pH of the membrane is about 5.0 to about 6.0. It is surprising that such membranes can be formed, since it was previously assumed that chitosan precipitates only when the pH of chitosan dissolved in a liquid composition exceeds 6.3. In another embodiment, the membrane has a pH of about 4.0 to about 6.5, preferably 4.0 to 6.0, even more preferably about 4.0 to about 5.4, most preferably about 4.0 to about 5.2, or even about 4.0 to about 5.0.

[0147] Therefore, one way to precipitate chitosan would be to add an alkaline solution to the composition or to use a volatile acid, such as acetic acid, as a solvent for chitosan. The volatile acid evaporates after each solution of chitosan is applied to the skin, thereby raising the pH to above 6.3 and precipitating chitosan. Surprisingly, it has been found that when the film is obtained by applying the liquid composition of the present invention to the skin of a subject, it is not necessary to add an alkaline solution or dissolve chitosan in a volatile acid to raise the pH to above 6.3.

[0148] Thus, in a preferred embodiment, the liquid compositions of the present invention are free of volatile acids such as acetic acid, the use of which is undesirable in the compositions because consumers may consider the odor of volatile acids to be unpleasant.

[0149] In a preferred embodiment, the liquid composition has a pH of about 4.5 to about 6.0. In another preferred embodiment, the liquid composition has a pH of about 4.5 to about 5.5. A low pH is required for the liquid composition to dissolve chitosan or a salt thereof for application to the skin.

[0150] Thus, in another preferred embodiment, the membrane is homogeneous.

[0151] In another preferred embodiment, the film covers an area of ​​at least 1 mm x 1 mm, preferably at least 2 mm x 2 mm. Thus, the film covers a larger area of ​​skin than, for example, a single nanoparticle of chitosan encapsulating a drug. The nanoparticles do not form a uniform layer of film when applied to the skin. Instead, they only produce small areas of nanocapsules "nanopatches" on the skin. The use of chitosan nanoparticles in this way has the disadvantage that they cannot uniformly cover skin areas as they can with a film.

[0152] In another preferred embodiment, the film is formed within 5 minutes after applying the composition to the skin under standard conditions of 25° C. and 101.3 kPa.

[0153] In another preferred embodiment, 1 cm of skin 2 It is sufficient to apply 0.1 μl to 10 μl of the liquid composition per application. In another preferred embodiment, the liquid composition dries on the skin within 10 s to 300 s, so that the liquid composition is not absorbed by or transferred to a substance in contact with the film on the skin.

[0154] Surprisingly, it has been found that evaporation or uptake of solvent from the applied gel-like chitosan solution promotes and accelerates the formation of an insoluble film on the skin surface by lowering the pH through dilution and increasing the pH through concentration.

[0155] In another embodiment, the membrane comprises at least 10% (w / w) chitosan or a salt thereof, based on the total weight of the membrane.

[0156] In another preferred embodiment, the membrane is permeable to the at least one agent, thereby allowing the membrane to function as a carrier for the at least one additional agent while simultaneously protecting the skin underneath from undesirable stressors, such as alkaline agents, UV radiation, other chemicals or direct contact with clothing that may further irritate the skin.

[0157] In another preferred embodiment, the film formed by the liquid composition of the present invention is permeable to the at least one additional drug, so that the film acts as a carrier for the at least one additional drug. At the same time, the film formed by the liquid composition of the present invention can be coated with cosmetic suspensions, emulsions, foams, liquids, gels and oils that do not contain the liquid composition of the present invention.

[0158] In another preferred embodiment, the skin is first treated with a cosmetic suspension, emulsion, foam, liquid, gel or oil without the liquid composition of the present invention, followed by application of the film-forming liquid composition of the present invention.

[0159] In another preferred embodiment, the skin is first treated with cosmetic suspensions, emulsions, foams, liquids, gels and oils without the liquid composition of the present invention, followed by application of the liquid composition of the present invention which forms a film, and the resulting film can then be simultaneously covered with the cosmetic suspensions, emulsions, foams, liquids, gels and oils.

[0160] In another preferred embodiment, the membrane formed by the liquid composition of the present invention is permeable to said at least one further drug, so that said membrane acts as a carrier for said at least one further drug and can be simultaneously coated with medicinal suspensions, emulsions, foams, liquids, gels and oils containing said drug.

[0161] In another preferred embodiment, the skin is first treated with a medicated suspension, emulsion, foam, liquid, gel or oil, followed by application of the film-forming liquid composition of the present invention.

[0162] In another preferred embodiment, the skin is first treated with the medicated suspensions, emulsions, foams, liquids, gels and oils, followed by application of the film-forming liquid composition of the present invention, and the resulting film can then be simultaneously covered with the medicated suspensions, emulsions, foams, liquids, gels and oils.

[0163] Use of said liquid cosmetic composition for skin care applications In a fourth aspect, the present invention relates to the use of a liquid composition as described in the previous aspects for skin care applications, i.e. for cosmetic purposes, said liquid composition being topically applied to an area of ​​the skin of a subject, thereby forming a film of the present invention, said film having a cosmetic purpose, hereinafter referred to as a cosmetic film.

[0164] Preferably, said skin care is abrasion care, cut wound care, pimple care, blister care, puncture wound care, burn care, anti-ageing applications, rash care, irradiated skin care, laser treatment care, plasma treatment care, tattoo and tattoo removal care, skin suffering from viral infections, skin peeling care or prevention, irradiation induced skin changes care or prevention, skin scar tissue formation care or prevention, dry skin prevention, oily skin prevention, skin crack prevention, stretch mark prevention, reduction of skin wrinkles, thin skin prevention or skin cleansing applications or prevention of their associated symptoms.

[0165] Particularly preferably, the skin care application is an anti-aging application, treatment of rashes, treatment of dry skin, reduction of skin wrinkles, prevention of skin thinning, prevention of skin cracks, treatment of stretch marks or skin cleansing application.

[0166] Particularly preferably, said skin care applications are the care of abrasions, the care of cracks, the care of cuts, the care of pimples, the care of blisters, the care of puncture wounds, the care or prevention of the formation of skin scar tissue or the prevention of associated symptoms thereof.

[0167] The associated symptoms of any of the above skin care applications may be skin soreness, itchiness, wet feeling, odor, roughness, crackiness, fissures, dryness, discoloration, peeling or other unpleasant stress symptoms or combinations thereof. In a preferred embodiment, the skin care application is the care of rashes or dry skin. In another preferred embodiment, the liquid cosmetic composition is used for the care of oily skin.

[0168] In a third aspect, the present invention also relates to the use of the cosmetic film for skin care.Preferably, said skin care is for the care of abrasions, the care of cuts, the care of pimples, the care of blisters, the care of puncture wounds, the care of burns, anti-aging applications, the care of rashes, the care of irradiated skin, the care of laser treatment, the care of plasma treatment, the care of tattoos and tattoo removal, the care of skin suffering from viral infections, the care or prevention of skin peeling, the care or prevention of irradiation-induced skin changes, the care or prevention of the formation of skin scar tissue, the prevention of dry skin, the prevention of oily skin, the prevention of skin cracks, the prevention of stretch marks, the reduction of skin wrinkles, the prevention of skin thinning, or the use of skin cleansing or the prevention of their associated symptoms.

[0169] Particularly preferably, the skin care application is an anti-aging application, treatment of rashes, treatment of dry skin, reduction of skin wrinkles, prevention of skin thinning, prevention of skin cracks, treatment of stretch marks or skin cleansing application.

[0170] Particularly preferably, said skin care applications are the care of abrasions, the care of cracks, the care of cuts, the care of pimples, the care of blisters, the care of puncture wounds, the care or prevention of the formation of skin scar tissue or the prevention of associated symptoms thereof.

[0171] The associated symptoms of any of the above skin care applications may be skin soreness, itchiness, wetness, odor, roughness, cracking, chapped skin, dry skin, discoloration or other unpleasant stress symptoms or a combination thereof.

[0172] In a preferred embodiment, the skin care application is the treatment of rashes or dry skin.

[0173] In another preferred embodiment, the cosmetic film is used for the care of oily skin.

[0174] In another aspect, the present invention relates to the use of said liquid composition as a pharmaceutical product.

[0175] Disinfectants In a preferred embodiment of the present invention, the liquid composition with chitosan comprises a disinfectant, which comprises an alcohol, an aldehyde, iodine, chlorine, a quaternary ammonia compound, a peroxide, an amphoteric surfactant, a phenol, an alkylamine, an acid and / or a base. Providing a disinfectant at the same time is particularly advantageous when disinfection is required. The liquid composition with chitosan promotes the re-establishment of a healthy microbiome after disinfection and / or inhibits the growth of pathogenic microorganisms.

[0176] Alcohol disinfectants include ethanol, propanol, and isopropanol. Aldehyde disinfectants include formaldehyde, glutaraldehyde, and glyoxal. Iodine compounds are synonymous with iodophors and include compounds that release iodine. Chlorine includes free chlorine or compounds that release chlorine, such as hypochlorite-releasing compounds (e.g., alkaline hypochlorite, hypochlorous acid).

[0177] Examples of quaternary ammonia compounds include guanides, biguanides, guanidine salts, and bisbiguanides such as chlorhexidine, polyhexamethyl biguanide, polyhexamethylene guanidine hydrochloride, polyhexamethylene guanidine hydrophosphate, and poly[2-(2-ethoxy)-ethoxyethyl]-guanidinium chloride. Examples of peroxides include hydrogen peroxide, peracetic acid, benzoyl peroxide, sodium perborate, potassium permanganate, and perbenzoic acid. Examples of alkylamines include primary, secondary, and tertiary alkylamines. A representative alkylamine is N,N-bis-(3-aminopropyl)laurylamine. Examples of acids include organic and inorganic acids. Examples of organic acids include formic acid, phenylacetic acid, acetic acid, citric acid, and propionic acid. Further acids include protonated carboxylic acids (e.g., heptane, octane, nonane, decane, undecane), acid anions (e.g., alkylarylsulfonic acids, arylsulfonic acids, alkylsulfonic acids, alkylarylsulfuric acids, arylsulfuric acids, alkylsulfuric acids, alkylarylsulfuric acids), and chlorine dioxide from alkaline chlorite with acid activators. Bases include sodium hydroxide, potassium hydroxide, and calcium hydroxide. Phenolic disinfectants may be selected from 2,4,4"-trichloro-2'-hydroxydiphenyl ether, known as triclosan and commercially available, and 4-chloro-3,5-dimethylphenol, also known as PCMX. Further conventional disinfectants include copper sulfate, zinc sulfate, and sulfamethazine. Amphoteric surfactants include N-alkyl-di(-aminoethyl)-glycine and N-alkylaminopropylglycine.

[0178] The product list contains 1 of the following ingredients:ACTIL Haendedesinfection AHD 2000. Alcoman. ALCOSYN Viral、Bojasept、C 20、C 25、Calgonite Des-H、Calgonite Tooth Disinfection、Chirosyn Tooth Disinfection、CimoCid、CimoCid Sensitive、CimoSept Tooth、CimoSkin、Decontaman、Dermasept、Dermocol Gel New、Dermocol New Colorless、Descoderm、Descoderm viral、Desderman pure、Desderman care、Desmanol N、Desmanol pure、Desmanol care、DESTAsept DERM pro、DESTAsept MAN pro、DESTAsept rapid N、Ethasept、FAVORITE Nail Sanitizer、FAVORITE Nail Sanitizer+ Gel、Halasept 792、Halasept 820 Gel、Halasept 880 E、HD 410、HD 412 Essential、Herwe Dermasept N Gel、Herwe Dermasept N Liquid, Hospisept, Kaniderm, Kaniderm Premium, Kaniderm Protect, Kodan Tincture forte, L+R Handdisinfect Blue, L+R Handdisinfect Gel, L+R Handdisinfect Green, Lerasept(Polymer) HD, Manocid, Manorapid basic Manorapid Plus Manorapid rfu Manorapid Synergy ManuPep CARE ManuPepGEL, ManuPep Hand Disinfection, Manusept basic, marina-KC Opydes, MEDIman H2, Mucasept Plus, MYXAL® SEPT 70, MYXAL® SEPT 80, MYXAL® SEPT Ge, Neosept, Neoseptin, octeniderm, Op Sept, Op Sept Basic, Pluraman GEL, Pluraman SOFT, Poly-Alcohol Hands, Antisepticum, Promanum pure, Protectasept Skin and Hand Disinfection, PuraDES PentaMAN B, PuraDES Pentra MAN, PuraDES TeraMAN GEL, PuraDES TetraMAN, PuraDES TetraMAN B, REGOskin DS 4051, Sanocid, Sanocid Gel, Sanocid Plus, sensiva Hand Disinfection, septDES FOAM, septDES FOAMSOAP, septDES GEL, Septiderm, septLIQUID PLUS, septLIQU, ID SENSITIVE, Skinman clear, Skinman complete, Skinman complete pure, Skinman foam, Skinman soft, Skinman soft protect, Skinman soft protect FF, Skinsept F, SKINTASTIC Leocid Sept, Soft Care Des E, Soft Care Des E Foam, Soft Care Des E Spray, Soft Care Med, Softa-Man acute, Softa-Man pure, Softa-Man ViscoRub, Spitacid, Sterillium, Sterillium classic pure, Sterillium med, Sterillium Tissues, Sterillium Virugard, Sterillium® pure, Sure Instant HandSanitizer, triformin safeDIS, weigoman, weigoman parfuemfrei, weigoman pure and Witty-Lavalin D.

[0179] ectodermal tissue In a preferred embodiment, the ectodermal tissue is skin. In a more preferred embodiment, the ectodermal tissue is epidermis. In another preferred embodiment, the ectodermal tissue is damaged epidermis, and the damage is sunburn, acne, cuts, abrasions, incisions, pimples, blisters, puncture wounds, burns, aging, rashes, irradiated skin, laser-treated skin, plasma-treated skin, tattoos, tattoo removal, skin peeling, scar tissue, dry skin, oily skin, cracks, stretch marks, or wrinkles. In a more preferred embodiment, the ectodermal tissue, skin, epidermis, or damaged epidermis of the subject has been previously sterilized or disinfected. The use of the liquid composition with chitosan is particularly advantageous after disinfection, since the liquid composition with chitosan promotes the re-establishment of a healthy microbiome after disinfection and / or inhibits the growth of pathogenic microorganisms.

[0180] In another preferred embodiment, said ectodermal tissue is stressed epidermis, said stress being caused by prostheses, endoprostheses, braces, reinforced exoskeletons, bandages, compression dressings, stockings, bandages, latex protective materials, massagers, ventilation masks, anti-apnea measures, work or protective clothing, gloves, pacifiers, tight clothing or shoes, disinfectants, cosmetic procedures, cosmetics, preservatives, detergents, sweat, lack of personal hygiene, lying or sitting for long periods of time, wound dressings, sunburn, burns, puncture wounds, irradiation, laser treatment, plasma treatment, getting a tattoo and / or removing a tattoo.

[0181] Preferably, said stress is caused by massagers, work or protective clothing, gloves, pacifiers, tight clothing or shoes, cosmetic treatments, cosmetics, preservatives, detergents, sweat, lack of personal hygiene, sunburn, burns, puncture wounds, irradiation, laser treatment, plasma treatment, getting a tattoo and / or removing a tattoo.

[0182] Work or protective clothing includes boots, airtight protective suits, masks, helmets, gloves, respirators, etc. Latex protective materials include, for example, latex gloves.

[0183] Preferably, said stress is caused by a prosthesis, an endoprosthesis, a brace, a reinforced exoskeleton, a bandage, a pressure bandage, a stocking, a dressing, a latex protective material, a massager, a ventilation mask, a work or protective suit, gloves, prolonged lying or sitting position or a wound dressing.The underlying cause of such stress is the limitation of water and gas exchange in the skin or epidermis.

[0184] The prolonged lying or sitting state may be due to hospitalization or sitting in a wheelchair. Symptoms include pressure sores (or pressure sores and pressure ulcers). Thus, preferably, the stress may be caused by pressure sores, more preferably by pressure sores.

[0185] Cosmetic skin treatments include, for example, peels with abrasives, acids and laser treatments.

[0186] Stress caused by cleaning agents may result from work, hobbies, sports or household chores where the skin comes into contact with the cleaning agent.

[0187] In another aspect, the present invention provides a kit comprising the liquid cosmetic composition of any of the above aspects, further comprising a disinfectant, in a preferred embodiment, the disinfectant is selected from the group comprising an alcohol, an aldehyde, iodine, chlorine, a quaternary ammonium compound, a peroxide, an amphoteric surfactant, a phenol, an alkylamine, an acid and / or a base.

[0188] Compositions Comprising Chitosan for the Treatment of Dysbiosis - Patent application The following embodiment relates to the fifth aspect of the present invention, namely a pharmaceutical composition comprising chitosan for the treatment of dysbiosis.

[0189] Surprisingly, the inventors of the present invention have found that the liquid composition with chitosan described above is also useful in the treatment of diseases or disorders related to the microbiome, for example in the treatment of dysbiosis. Therefore, in this respect, the liquid composition with chitosan is referred to as a pharmaceutical composition with chitosan in liquid form. The differential promotion of a healthy microbiome eliminates or reduces the possibility of infection of other skin areas, infection of other individuals, and contamination of other individuals, droplets, and surfaces. As with cosmetic applications, the promotion of a healthy microbiome is considered to be particularly beneficial after or at the same time as disinfection or sterilization, i.e., the intentional removal of a (healthy) microbiome, which may be required before medical procedures such as surgery, injections, or catheter applications.

[0190] In one embodiment, the pharmaceutical composition comprises chitosan in a liquid form for use in treating dysbiosis of an ectodermal tissue of a subject. In another embodiment, treating dysbiosis includes modulating a microbial taxon of an ectodermal tissue of a subject. In a preferred embodiment, modulating a microbial taxon includes increasing or decreasing the abundance of a taxon. In another preferred embodiment, modulating a microbial taxon includes increasing or decreasing the abundance of the taxon relative to the abundance of the microbial taxon in the absence of the liquid composition. In another preferred embodiment, modulating a microbial taxon includes increasing or decreasing the abundance of the taxon relative to the abundance of a second microbial taxon.

[0191] In another preferred embodiment, the pharmaceutical composition differentially promotes the growth of one or more microbial taxa relative to another microbial taxa. In a more preferred embodiment, the pharmaceutical composition promotes the growth of one or more beneficial microbial taxa over one or more pathogenic microbial taxa. In another more preferred embodiment, the pharmaceutical composition promotes the growth of one or more beneficial microbial taxa while at the same time not harming said one or more pathogenic microbial taxa. In another more preferred embodiment, the pharmaceutical composition promotes the growth of one or more beneficial microbial taxa while at the same time inhibiting the growth of said one or more pathogenic microbial taxa. In yet another preferred embodiment, the pharmaceutical composition with chitosan does not harm the growth of one or more beneficial microbial taxa but inhibits the growth of one or more pathogenic microbial taxa.

[0192] The beneficial microbial taxa include Staphylococcus epidermidis, Staphylococcus mitis, Staphylococcus capitis, Corynebacterium specs., Propionibacterium acnes, Malassezia pachydermatis, Streptococcus spec., Streptococcus spec., Lactobacillus spec., Micrococcus spec. and Bacillus spec.

[0193] The pathogenic microbial taxa include Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Enterococcus faecalis / faecium, E. coli, Klebsiella pneumoniae, Candida albicans, Microsporum canis, Acinetobacter baumanii, Staphylococcus intermedius, and Staphylococcus pseudointermedius.

[0194] In some cases, beneficial taxa are transformed into pathogenic taxa, which may occur depending on their abundance, i.e. when they occur in increased numbers compared to the healthy state of the microbiome. In this embodiment, the pathogenic taxa may further include Propionibacterium, Steptrococcus spec. (e.g. in the case of acne) or Propionibacterium, Corynebacterium, Staphylococcus spec., Streptococcus spec., in particular Staphylococcus aureus and Staphylococcus epidermidis (e.g. in the case of psoriasis).

[0195] The pharmaceutical composition comprising chitosan may be any of the compositions previously described in the section "Liquid composition comprising chitosan". Since the liquid compositions are the same, all aspects relating to the film formed by the liquid composition described in the section "Film formed by the liquid composition comprising chitosan" apply equally to the film formed by the pharmaceutical composition comprising chitosan.

[0196] In a particularly preferred embodiment, the pharmaceutical composition comprising chitosan for use in the treatment of dysbiosis further comprises glycolic acid and / or lactic acid. In a particularly preferred embodiment, the pharmaceutical composition comprising chitosan for use in the treatment of dysbiosis further comprises glycolic acid. In a particularly preferred embodiment, the pharmaceutical composition comprising chitosan for use in the treatment of dysbiosis further comprises lactic acid.

[0197] In a particularly preferred embodiment, the pharmaceutical composition comprising chitosan for use in the treatment of dysbiosis further comprises glycolic acid and lactic acid.

[0198] In an even more preferred embodiment, the pharmaceutical composition comprising chitosan for use in the treatment of dysbiosis comprises, relative to the total weight of the pharmaceutical composition: 0.010-4.0% (w / w) chitosan, 0.005 to 2.5% (w / w) glycolic acid, 0.005 to 2.5% (w / w) lactic acid, has.

[0199] In an even more preferred embodiment, the pharmaceutical composition comprising chitosan for use in the treatment of dysbiosis comprises, relative to the total weight of the pharmaceutical composition: 0.20-4.0% (w / w) chitosan, 0.05 to 2.5% (w / w) glycolic acid, 0.05 to 2.5% (w / w) lactic acid, Yes.

[0200] In yet another more preferred embodiment, the pharmaceutical composition comprising chitosan for use in the treatment of dysbiosis comprises, based on the total weight of the pharmaceutical composition: 0.20-4.0% (w / w) chitosan, 0.05 to 2.5% (w / w) glycolic acid, 0.05 to 2.5% (w / w) lactic acid, the degree of acetylation of chitosan is 2.5% or less, preferably 2.0% or less; and the pH of said liquid cosmetic composition is from about 4.0 to about 6.5.

[0201] In yet another more preferred embodiment, the pharmaceutical composition comprising chitosan for use in the treatment of dysbiosis comprises, based on the total weight of the pharmaceutical composition: 2.7-3.3% (w / w) chitosan, 0.5-1.3% (w / w) glycolic acid, 0.5-1.3% (w / w) lactic acid, the degree of acetylation of chitosan is 2.5% or less, preferably 2.0% or less; and the pH of said liquid cosmetic composition is from about 4.0 to about 6.5.

[0202] In an even more preferred embodiment, the pharmaceutical composition with chitosan comprises a disinfectant, which may include alcohol, aldehyde, iodine, chlorine, quaternary ammonia compounds, peroxides, amphoteric surfactants, phenols, alkylamines, acids and / or bases. Providing a disinfectant at the same time is particularly advantageous when disinfection is required. The liquid composition with chitosan promotes the re-establishment of a healthy microbiome after disinfection, i.e., eubiosis, and / or inhibits the growth of pathogenic microorganisms. In general, the specific disinfectants described in the "Disinfectant" section are equally applicable to the pharmaceutical composition with chitosan.

[0203] In one embodiment, the dysbiosis is idiopathic. Idiopathic means that the subject has substantially no observable cause of the dysbiosis. In another embodiment, the dysbiosis is associated with a disease, disorder, or condition of the subject. In some embodiments, the disease, disorder, or condition includes, for example, an infectious disease, an inflammatory disease, a metabolic disease, an autoimmune disease, or a cancer. Preferably, the disease, disorder, or condition includes, for example, an infectious disease, an inflammatory disease, or an autoimmune disease. In some embodiments, the infectious disease is a viral, bacterial, and / or fungal skin infection. Viral skin infections include herpes simplex (herpes labialis and herpes genitalis), herpes zoster (shingles), warts, and molluscum contagiosum.

[0204] Bacterial skin infections include, for example, cellulitis, erysipelas, impetigo, folliculitis, and furuncles and carbuncles. Cellulitis is an infection of the dermis and subcutaneous tissue, has an unclear border, and is usually caused by Streptococcus or Staphylococcus species. Erysipelas is a shallow form of cellulitis, has a clear border, and is caused exclusively by Streptococcus. Impetigo is also caused by Streptococcus or Staphylococcus, and may cause the stratum corneum to elevate, producing the common blister effect. Folliculitis is an inflammation of the hair follicle. Fungal skin infections include infections caused by yeasts (such as Candida or Malassezia furfur) or dermatophytes such as Epidermophyton, Microsporum, or Trichophyton.

[0205] In some embodiments, inflammatory diseases include, for example, inflammatory bowel disease (IBD), ulcerative colitis (UC), Crohn's disease (CD), idiopathic inflammation of the small intestine, indeterminatal colitis, pouchitis, irritable bowel syndrome (IBS), necrotizing enterocolitis (NEC), enteritis, constipation, microscopic colitis, diarrhea, graft-versus-host disease (GVHD), allergies (e.g., food allergies), pseudomembranous colitis, dyspepsia, non-ulcer dyspepsia, diverticulosis, diverticulitis, ischemic colitis, radiation colitis, radiation enteritis, collagenous colitis, gastroenteritis, or polyps. In some embodiments, metabolic disorders include, for example, obesity, (insulin resistance) pre-diabetes, type II diabetes, high fasting blood glucose (hyperglycemia), metabolic syndrome, or cardiovascular risk factors (e.g., high blood cholesterol levels, high LDL, high blood pressure (hypertension), high triglyceride levels, low HDL).

[0206] In some embodiments, the autoimmune disease includes, for example, Crohn's disease, psoriasis, allergies, asthma, hives, or atopic dermatitis, hi some embodiments, the cancer is a cancer of the skin.

[0207] In general, diseases, disorders and conditions associated with dysbiosis are described and can be found in "Skin Signs of Systemic Disease", Saunders, 1998.

[0208] In some embodiments, the dysbiosis is associated with or is a result of immune deficiency or immunosuppression, immunosuppression, administration of antibiotics, chemotherapeutic agents, antibodies, cytokines, cellular therapeutic agents, therapeutic nucleic acids, immunosuppressants, burns or irradiation of the skin, stress on the skin, body, or parts thereof.

[0209] In a preferred embodiment, the stress may be, for example, stress caused by prostheses, endoprostheses, braces, reinforced exoskeletons, bandages, pressure bandages, stockings, bandages, latex protective materials, ventilation masks, lying or sitting for a long time, or wound dressings. Lying or sitting for a long time may be caused by hospitalization or sitting in a wheelchair. Symptoms caused by lying or sitting for a long time include bedsores. Therefore, preferably, the stress may be caused by bedsores. More preferably, the stress may be a pressure ulcer.

[0210] In an even more preferred embodiment, the subject's ectodermal tissue, skin, epidermis, damaged or stressed epidermis, acute or chronic wounds are sterilized or disinfected beforehand.In other words, if the subject's skin is disinfected with one of the above disinfectants, the pharmaceutical composition comprising chitosan is applied to the subject's skin immediately after disinfection.If a medical procedure is required after disinfection, the pharmaceutical composition comprising chitosan is applied to the subject's skin immediately after the medical procedure performed after the first disinfection.Optionally, another disinfection step may be performed after the medical procedure.

[0211] Further preferred embodiments of the present invention relate to:

[0212] 1. A pharmaceutical composition comprising chitosan in a liquid dosage form for use in treating dysbiosis of ectodermal tissue in a subject.

[0213] 2. A pharmaceutical composition for use according to 1, wherein the treatment of dysbiosis comprises modulating the microbial taxa of the ectodermal tissue of the subject.

[0214] 3. A pharmaceutical composition for use according to 2, wherein modulating a microbial taxon comprises increasing or decreasing the abundance of said taxon.

[0215] 4. The pharmaceutical composition for use of 3, wherein modulating microbial taxa includes increasing the abundance of beneficial taxa relative to the abundance of pathogenic taxa.

[0216] 5. The pharmaceutical composition for use of 3, wherein modulating microbial taxa comprises reducing the abundance of pathogenic taxa while not substantially altering the abundance of beneficial taxa.

[0217] 6. A pharmaceutical composition for use according to 4 or 5, wherein the beneficial microbial taxa include Staphylococcus epidermidis, Staphylococcus mitis, Staphylococcus capitis, Corynebacterium specs., Propionibacterium acnes, Malassezia pachydermatis, Streptococcus spec., Streptococcus spec., Lactobacillus spec., Micrococcus spec. and Bacillus spec.

[0218] 7. A pharmaceutical composition for use according to 4 or 5, wherein the pathogenic microbial taxa include Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Enterococcus faecalis / faecium, E. coli, Klebsiella pneumoniae, Candida albicans, Microsporum canis, Acinetobacter baumanii, Staphylococcus intermedius and Staphylococcus pseudointermedius.

[0219] 8. A pharmaceutical composition for use according to 1 to 7, further comprising urea, glycolic acid, glyoxylic acid, glycerol, pentylene glycol, lactic acid, ascorbic acid, pyroglutamic acid, citric acid, tartaric acid, fumaric acid, succinic acid, malic acid, mandelic acid, aloe vera, rosa gallica, hyaluronic acid, salicylic acid, gallic acid, cellulose and derivatives thereof, pectin and derivatives thereof, gum arabic, dextrin, cyclodextrin, xanthan gum, thiocyanates, amino acids, sorbic acid, sodium chloride, or combinations thereof.

[0220] 9. A pharmaceutical composition for use according to 1 to 7, further comprising glycolic acid and / or lactic acid.

[0221] 10. The composition comprises, based on the total weight of the liquid cosmetic composition: 0.01-4.0% (w / w) chitosan, 0.05 to 2.5% (w / w) glycolic acid, 0.05 to 2.5% (w / w) lactic acid, 9. A pharmaceutical composition for use according to claim 9.

[0222] 11. A pharmaceutical composition for use according to 8 to 10, wherein the composition comprises a disinfectant.

[0223] 12. The pharmaceutical composition for use according to claim 11, wherein the disinfectant comprises an alcohol, an aldehyde, iodine, chlorine, a quaternary ammonia compound, a peroxide, an amphoteric surfactant, a phenol, an alkylamine, an acid and / or a base.

[0224] 13. The pharmaceutical composition for use according to 1 to 12, wherein the ectodermal tissue is skin.

[0225] 14. The pharmaceutical composition for use according to 1 to 12, wherein the ectodermal tissue is epidermis.

[0226] 15. A pharmaceutical composition for use according to claim 14, wherein the epidermis is damaged epidermis.

[0227] 16. A pharmaceutical composition for use according to claim 15, wherein the injury comprises an acute or chronic wound.

[0228] 17. A pharmaceutical composition for use according to 1 to 16, wherein the subject's ectodermal tissue, skin, epidermis, damaged epidermis, acute or chronic wound has been sterilized or disinfected beforehand.

[0229] 18. The pharmaceutical composition for use of 1 to 17, wherein the dysbiosis is idiopathic (e.g., the subject has substantially no observable cause of the dysbiosis).

[0230] 19. A pharmaceutical composition for use according to 1 to 17, wherein the dysbiosis is associated with a disease, disorder or condition of the subject.

[0231] 20. A pharmaceutical composition for use according to claim 19, wherein the disease, disorder or condition comprises an infectious disease, an inflammatory disease, a metabolic disease, an autoimmune disease or cancer.

[0232] 21. The pharmaceutical composition for use according to claim 20, wherein the infectious disease is a viral, microbial and / or fungal skin infection.

[0233] 22. The pharmaceutical composition for use according to claim 20, wherein the autoimmune disease is Crohn's disease, psoriasis, allergy, asthma, urticaria or atopic dermatitis.

[0234] 23. A pharmaceutical composition for use according to 1 to 17, wherein said dysbiosis is associated with or is the result of immunodeficiency or immunosuppression, immunosuppression, burns or irradiation of the skin, stress of the skin, body or parts thereof.

[0235] 24. A pharmaceutical composition for use as claimed in claim 23, wherein said stress on the skin comprises stress caused by a prosthesis, an endoprosthesis, a brace, a reinforced exoskeleton, a bandage, a pressure bandage, a stocking, a dressing, a latex protective material, a ventilation mask, lying or sitting for an extended period of time, or a wound dressing.

[0236] 25. A pharmaceutical composition for use according to 1 to 17, wherein the dysbiosis is associated with or results from the administration of a medicament.

[0237] 26. A pharmaceutical composition for use according to claim 25, wherein the medicament comprises an antibiotic, a chemotherapeutic agent, an antibody, a cytokine, a cell therapy agent, a therapeutic nucleic acid or an immunosuppressant.

[0238] 27. The pharmaceutical composition for use according to claim 23, wherein the irradiation is ultraviolet irradiation, gamma irradiation, electron beam irradiation, X-rays or sunlight.

[0239] 28. A kit comprising chitosan in a liquid formulation according to any of the preceding claims, further comprising a disinfectant preferably selected from the group comprising alcohols, aldehydes, iodine, chlorine, quaternary ammonium compounds, peroxides, amphoteric surfactants, phenols, alkylamines, acids and / or bases.

[0240] definition As used herein, the terms "dissolved," "dissolution," and the like, with respect to a polymer, are intended to mean the solution of the polymer in an aqueous environment without molecular weight reduction in polymer chain length, and are thus distinct from "degradation," which is the process of reduction in molecular weight by depolymerization of the polymer.

[0241] The term "film" as used herein means a film-like barrier with selective permeability that is applied on the skin and may have cosmetic or medical properties. However, the entire film may be removed from the skin and therefore may exist in a state separated from the skin. In the present invention, the term "film" also indicates that the thickness of the film is preferably very thin, i.e., 50 μm or less. In contrast, the more comprehensive term "film" or "cosmetic film" also includes much thicker layers of cosmetics applied topically to the skin. With regard to chitosan, this may mean that a "cosmetic film" is achieved when the chitosan is not precipitated and the cosmetic composition is simply applied as a thick layer of, for example, a gel or cream, whereas in each "film", the chitosan is precipitated to form a film (optionally as a separate layer within said cosmetic film). A "cosmetic film" is not intended to treat any particular disease. A "medical film" is intended to treat a particular disease.

[0242] As used herein, the term "% acetylation degree" or "% DA", such as in "20% acetylation degree", refers to the number of acetylated -NN2 groups relative to the total number of -NH2 groups present in the polymer. For example, if 20 -NH2 groups are acetylated in a polymer, and the polymer has a total of 100 -NH2 groups including the 20 acetylated -NH2 groups, then the polymer has a degree of acetylation of 20%.

[0243] As used herein, the term "area," as in "an area of ​​the skin of a subject," refers to an upper surface area of ​​the skin of a subject. The subject may be a human or an animal, preferably a human.

[0244] The term "ectodermal tissue" refers to any ectoderm-derived tissue. Thus, superficial / external ectodermal tissue includes, but is not limited to, the following cells, structures and tissues: pluristratified epidermis, epidermis of the skin including glands, hair and nails (keratinocytes), epithelium of the mouth and nasal cavity, as well as salivary glands, enamel, epithelium of the pineal and pituitary glands, lens and cornea, and apical ectodermal ridge.

[0245] The term "skin" as used herein means the outer layer of the body, preferably the human body, and the term "skin" may include skin with and / or without hair. Thus, the skin is, for example, any kind of skin of the face, neck, mouth, throat, mucous membranes, chest, arms, legs and skin covering other parts of the body, which may be hairless or may have at least some body hair, such as arm or leg hair. However, in a preferred embodiment, the term "skin" also includes the scalp. In another embodiment, the term "skin" does not include the scalp. The skin may be human or animal skin, preferably human skin.

[0246] The term "epidermis" refers to the outermost layer of the skin, which provides a waterproof barrier and creates the skin's color. The dermis, below the epidermis, contains tough connective tissue, hair follicles, and sweat glands. Epidermal cells are defined as the epithelial cells that make up the epidermis. The epidermis comprises keratinized stratified squamous epithelium, which, from the dermis toward the outer surface, has a basal cell layer, a spinous cell layer, a granular layer, a lucid layer, and a stratum corneum.

[0247] As used herein, the term "cosmetic agent" refers to any substance intended to come into contact with various external parts of the human body, such as the epidermis, hair system, nails, lips and external genitalia, or the mucous membranes of the teeth and oral cavity, thereby cleaning them, perfume them, changing their appearance, and / or modifying body odor, and / or protecting or keeping them in good condition. Preferably, the cosmetic agent keeps the skin in good condition. Examples of cosmetic agents include, but are not limited to, emollients, humectants, colorants, pigments, fragrances, moisturizers, viscosity control agents, and any other cosmetic forming agents. Cosmetic agents are not intended to treat any particular disease.

[0248] As used herein, the term "cosmetic composition" refers to a preparation having at least one cosmetic agent intended to be in contact with various external parts of the human body, such as the epidermis, the hair system, the nails, the lips and the external genitalia, or the mucous membranes of the teeth and the oral cavity, thereby cleaning them, perfume them, modifying their appearance and / or modifying the body odor, and / or protecting or keeping them in good condition. Preferably, the cosmetic agent keeps the skin in good condition. The cosmetic agent is not intended to treat any particular disease.

[0249] As used herein, the term "liquid" refers to one of the four fundamental states of matter: liquid, solid, gas, and plasma. The term "liquid" also encompasses "semi-fluid states" such as gels, suspensions, dispersions, foams, emulsions, or gels.

[0250] As used herein, the term "pH of a cosmetic film" means the pH that can be measured when a drop of deionized water is applied to the cosmetic film and then the pH is measured on the wetted skin using a flat tip pH electrode.

[0251] The term "thickness" as used herein in relation to the thickness of a cosmetic film means the thickness of the layer formed by the cosmetic film on the upper surface of a substrate, e.g., skin. The thickness of a cosmetic film is determined by the volume of said liquid cosmetic composition and the chitosan concentration, e.g., 0.1-1 μl having a concentration of 0.5%-10% (w / w) relative to the total weight of the liquid cosmetic composition, and the area of ​​the subject's skin to which it is applied, e.g., 5 cm 2 , and the thickness of the film is about 1.5 g / cm 3 The density of the membrane can be assumed to be 25 cm. 2 For a skin area of ​​1 μl and an application volume of 1 μl, a thickness of 27 nm is calculated for a liquid cosmetic composition containing 10% (w / w) chitosan. Assuming that the film still has about 50% (w / w) water molecules, the thickness would double to about 54 nm.

[0252] Alternatively, the thickness of an isolated cosmetic film could be determined using an ellipsometer.

[0253] As used herein, the term "wetting agent" refers to a surfactant, a substance that increases the spreading properties of liquids by lowering surface tension, i.e., the tendency of molecules to adhere to one another.

[0254] As used herein, the term "skin care application" refers to any type of cosmetic treatment that keeps the skin in good condition or improves the condition of stressed or irritated skin, i.e., skin care applications do not improve the symptoms of a specific pathological condition such as psoriasis or other commonly known skin diseases.

[0255] As used herein, the term "sprayable liquid" means a liquid that can be applied to the skin as a spray from any type of commonly used cosmetic spray dispenser.

[0256] As used herein, "topically apply" means to apply or spread directly onto the skin, for example, by hand or with an applicator such as a wipe, puff, roller, foam or spray.

[0257] As used herein, the term "about" in, for example, "about 4.5 to 5.5" means that the value described immediately after "about" also includes slight deviations from the exact numerical value due to, for example, measurement errors.

[0258] As used herein, the term "cutaneous scar tissue" refers to scar tissue that replaces skin tissue, for example after the skin has been injured or after a surgical procedure in which the skin has been opened and the area has been replaced with scar tissue.

[0259] As used herein, the term "cutaneous scar tissue" refers to the types of wounds that occur when the skin is torn, cut, or punctured (open wounds), or when blunt trauma causes a bruise (closed wounds). Wounds often damage the epidermis of the skin. Wounds may include closed wounds that are in the process of healing.

[0260] As used herein, the term "microbiome" refers to the genetic material of a community of microorganisms that live in or on a subject (e.g., a human subject). The microorganisms include both persistent and transient inhabitants, such as eukaryotes, archaea, bacteria, and viruses (including bacterial viruses (e.g., phages)), and the "genetic material" includes genomic DNA, RNA such as ribosomal RNA and messenger RNA, epigenomes, plasmids, and all other types of genetic information. In some embodiments, the microbiome refers to the genetic material of a community of microorganisms, particularly in a niche.

[0261] As used herein, "microbiota" refers to a community of microorganisms occurring (persistently or transiently) in or on a subject (e.g., a human subject), including eukaryotes, archaea, bacteria, and viruses (including bacterial viruses, e.g., phages). In some embodiments, the microbiota refers specifically to a community of microorganisms in a niche.

[0262] As used herein, "bacterial flora" is synonymous with "microbiome" and "microbiota." The terms "microbiome" and "microbiota" are essentially different in their readouts. "Microbiome" is analyzed by genetic techniques such as PCR, whereas "microbiota" is analyzed by microbiological techniques such as growing the microorganisms on agar plates.

[0263] As used herein, "colonization" of a host organism refers to the non-transient establishment of bacteria or other microorganisms in a niche.

[0264] As used herein, the term "abundance," when referring to a microbial taxon, refers to the presence of one microbial taxon relative to another in a particular microbial niche, such as the gastrointestinal tract, or in the entire host organism (e.g., humans or experimental animal models of disease). The microbial taxon may be a bacterial taxon.

[0265] As used herein, the term "taxa" or "taxon" generally refers to a group of microorganisms considered as a single unit. Microorganisms may be divided into taxa according to the characteristics of the different types of hosts they serve.

[0266] As used herein, the terms "microorganism" or "microbial" generally refer to organisms that are too small to be seen by the naked eye. Examples of microorganisms include, but are not limited to, bacteria, archaea, fungi, protists, viruses, and microscopic animals.

[0267] As used herein, "dysbiosis" refers to the state of the microbiota under a disease state of the host, a predisposition to a disease of the host, or another undesirable state or condition of the host. In one embodiment, dysbiosis refers to the state of the microbiota under a disease state. Dysbiosis can be contrasted with regimen, which refers to the state of the microbiota under healthy conditions of the host. The state of the microbiota may include characteristics related to the structure or function of the microbiota. In one embodiment, dysbiosis encompasses an imbalance in the state of the microbiota, where the normal diversity of a microbial taxon or the relative abundance of the taxon to a second bacterial taxon or to the abundance of the taxon under healthy conditions is affected. In one embodiment, dysbiosis encompasses an imbalance in the function of the microbiota, e.g., a change in the level of gene expression, the level of a gene product, or the metabolic output (e.g., immune function, such as immune surveillance or inflammatory response). In some embodiments, dysbiosis is an undesirable, e.g., unhealthy, state associated with an undesirable condition in the host and no longer promotes health.

[0268] As used herein, "modulating the microbiota" or "modulating the microbiota" refers to changing the state of the microbiota. Changing the state of the microbiota may include changing the structure and / or function of the microbiota. A change in the structure of the microbiota is, for example, a change in the relative composition of taxa, for example, in one or more regions of the ectodermal tissue, skin or epidermis. In one embodiment, a change in the structure of the microbiota includes, for example, a change in the abundance of a taxa relative to another taxa or relative to the abundance that would be observed in the absence of the modulation. Modulation of the microbiota may also include, or may include in addition to, a change in the function of the microbiota, such as a change in the gene expression, gene product level (e.g., RNA or protein) or metabolic output of the microbiota. A function of the microbiota may include pathogen protection of the host, host nutrition, host metabolism and host immune modulation. Modulation of the structure or function of the microbiota may further result in a change in one or more functional pathways of the host (e.g., a change in gene expression, gene product levels and / or metabolic output of a host cell or host process) as a result of the change in the microbiota or its function.

[0269] As used herein, the term "pathogenic" (e.g., "pathogenic bacteria") refers to an agent, microorganism, or condition that has the potential to cause disease. In some contexts, pathogens also include microorganisms (e.g., bacteria) that are associated with a disease or condition, but for which a causal relationship (e.g., a direct causal relationship) with the disease or condition has not been established or needs to be established.

[0270] The term "phenotype" refers to a set of observable characteristics of an individual element. For example, an individual subject may have a phenotype that is "healthy" or "diseased." A phenotype may describe the state of an element, and all elements of a phenotype share the same set of characteristics that describe the phenotype. The phenotype of an individual is the result, in part or in whole, of the interaction of the element's genome and / or microbiome with the environment.

[0271] As used herein, the term "subject" or "patient" generally refers to any human or animal subject. Human does not denote a particular age or sex. A subject may include a pregnant woman. A subject may include a newborn (preterm newborn, full term newborn), infants up to 1 year of age, children (e.g., 1 to 12 years of age), teenagers (e.g., 13-19 years of age), adults (e.g., 20-64 years of age), and the elderly (65 years and older). A subject includes animals such as pets, agricultural animals, e.g., farm animals or livestock, e.g., cows, horses, sheep, pigs, chickens, etc., and wild animals. Generally, a subject has a host and its corresponding microbiota.

[0272] As used herein, the terms "treating" and "treatment" refer to the administration of an agent or composition to a subject (e.g., a symptomatic subject afflicted with an adverse condition, disorder, or disease) to affect a reduction in the severity and / or frequency of the condition, eliminate the condition and / or its underlying cause, and / or promote the amelioration or treatment of damage, and / or prevent an adverse condition, disorder, or disease in an asymptomatic subject predisposed to having, or at suspect or risk of developing, a particular adverse condition, disorder, or disease.

[0273] Finally, the present invention also relates to the following aspects:

[0274] 1. a) Chitosan or its salt, the degree of acetylation of which is 20% or less, and b) at least one further cosmetic agent; A liquid cosmetic composition comprising: The liquid cosmetic composition has a pH of about 4.0 to about 6.5.

[0275] 2. The liquid cosmetic composition according to 1, wherein the at least one additional cosmetic agent is selected from the group consisting of urea, glycolic acid, glyoxylic acid, glycerol, pentylene glycol, lactic acid, ascorbic acid, pyroglutamic acid, citric acid, tartaric acid, fumaric acid, succinic acid, malic acid, mandelic acid, aloe vera, rosa gallica, hyaluronic acid, salicylic acid, gallic acid, cellulose and its derivatives, pectin and its derivatives, gum arabic, dextrin, cyclodextrin, xanthan gum, thiocyanates, amino acids, sorbic acid, sodium chloride or combinations thereof.

[0276] 3. The liquid cosmetic composition described in 2, wherein the at least one additional cosmetic agent comprises glycolic acid and lactic acid.

[0277] 4. A liquid cosmetic composition according to any one of 1 to 3, wherein the chitosan is deacetylated in two or more steps.

[0278] 5. A liquid cosmetic composition according to any one of 1 to 4, wherein the degree of acetylation of chitosan is 15% or less, more preferably 10% or less, even more preferably 5% or less, or even more preferably 2.5% or less.

[0279] 6. A liquid cosmetic composition according to any one of 1 to 5, wherein the chitosan concentration is at least 0.1% to 15% (w / w), based on the total weight of the liquid cosmetic composition.

[0280] 7. The composition comprises, based on the total weight of the liquid cosmetic composition: 0.05% to 15% (w / w) chitosan, 0.0% to 9% (w / w) glycolic acid, 0.0% to 9% (w / w) lactic acid, 6. The liquid cosmetic composition according to any one of 1 to 5, comprising:

[0281] 8. The composition comprises, based on the total weight of the liquid cosmetic composition: 0.20-4.0% (w / w) chitosan, 0.0-2.5% (w / w) glycolic acid, 0.0-2.5% (w / w) lactic acid, 6. The liquid cosmetic composition according to any one of 1 to 5, comprising:

[0282] 9. The liquid cosmetic composition described in any one of 1 to 8, wherein the liquid cosmetic composition further comprises an emulsifier, a surfactant or a wetting agent.

[0283] 10. The liquid cosmetic composition according to claim 9, wherein the emulsifier, surfactant or wetting agent is selected from the group consisting of polysorbates, alkylamidobetaines, alcohol polyglucosides or combinations thereof.

[0284] 11. The liquid cosmetic composition described in any one of 1 to 10, wherein the liquid cosmetic composition further contains a preservative.

[0285] 12. The liquid cosmetic composition according to claim 11, wherein the preservative is sorbic acid as a free acid or a salt thereof.

[0286] 13. A liquid cosmetic composition described in any one of 1 to 10, wherein the liquid cosmetic composition does not contain a preservative.

[0287] 14. The liquid cosmetic composition according to any one of 1 to 13, wherein the liquid cosmetic composition is in the form of an emulsion, dispersion, suspension, serum, gel, solution, sprayable liquid, aerosol or foam.

[0288] 15. Use of a liquid cosmetic composition according to any one of 1 to 14 for skin care applications, wherein the liquid cosmetic composition is topically applied to an area of ​​a subject's skin to form a cosmetic film.

[0289] 16. The use of 15, wherein the skin care application is care of abrasions, care of cuts, care of pimples, care of blisters, care of puncture wounds, care of burns, anti-aging applications, care of rashes, care of irradiated skin, care of laser treatment, care of plasma treatment, care of tattoos and tattoo removal, care or prevention of skin peeling, care or prevention of irradiation induced skin changes, care or prevention of formation of skin scar tissue, prevention of dry skin, prevention of oily skin, prevention of cracked skin, prevention of stretch marks, reduction of skin wrinkles, prevention of skin thinning or skin cleansing applications or prevention of their associated symptoms.

[0290] 17. Use of 16, wherein the skin care application is the prevention of an associated symptom, the associated symptom being selected from the group consisting of epidermal pain, itchiness, wetness sensation, odor, roughness, cracks, chapped skin, dryness, deterioration of appearance, peeling or other unpleasant stress symptoms or combinations thereof.

[0291] 18. Use of 15, 16 or 17, wherein said cosmetic film forms a stable support for conventional make-up applied subsequent to formation of said cosmetic film without interfering with the visual effect.

[0292] 19. Use of any one of 15 to 18, wherein the cosmetic film has a pH of about 4.0 to about 6.

[0293] 20. The liquid cosmetic composition comprises, based on the total weight of the liquid cosmetic composition: 0.20-4.0% (w / w) chitosan, 0.0-2.5% (w / w) glycolic acid, 0.0-2.5% (w / w) lactic acid, Use of any one of 15 to 19. EXAMPLES

[0294] Example 1 Comparison of pH before and after cosmetic treatment with chitosan film-forming composition Solutions A and B of low acetylated chitosan with a degree of acetylation of 2% were prepared as follows:

[0295] Solution A (Ch-Lac / Gly) Chitosan 3.00% Glycolic acid 0.74% Lactic acid 0.88% Potassium sorbate 0.10% Glycerol 1.00% Polysorbate 20 0.25% pH 4.8

[0296] Solution B (Ch-Ac) Chitosan 3.00% Acetic acid 1.23% Potassium sorbate 0.10% Glycerol 1.00% Polysorbate 20 0.25% pH 5.0

[0297] All percentages above are w / w. Lactic acid and glycolic acid are well-known cosmetic moisturizers. Potassium sorbate is a well-known preservative and glycerol is an additional well-known humectant in cosmetic compositions. Polysorbate 20 is a well-known humectant.

[0298] For reference, solution C was prepared without chitosan.

[0299] Solution C(Na-Lac / Gly) Glycolic acid 0.74% Lactic acid 0.88% The pH was adjusted to 4.9 with NaOH.

[0300] All the above percentages are w / w. All solutions A, B and C have approximately the same pH value. Low acetylated chitosan with 2% acetylation was obtained according to

[0065] of EP2473202B1, but the parameters of the above process were adjusted to obtain an acetylation degree of 2%.

[0301] For further experiments, solutions A, B and C were diluted as described in Tables 1-3:

[0302] [Table 1]

[0303] [Table 2]

[0304] [Table 3]

[0305] To measure skin pH, the relevant area of ​​skin was wetted with a 50 μl drop of deionized water and the pH was measured using a calibrated flat-tip pH electrode (pH electrode HI14142 from Hanna Instruments GmbH) by contacting the pH electrode to the wetted skin.

[0306] The normal pH of the test subject's skin was pH 4.6, which was raised to pH 6.0 by washing with curd soap.

[0307] In addition, each diluted solution of A, B and C was applied to the skin and spread with the tip of a pipette to a depth of 5 cm. 2 After 3 minutes, the skin area was dried. It was estimated that at least for dilutions A and B, a film between 1 μm and 6 μm thick had formed. A 50 μl drop of deionized water was placed on the skin area and a pH electrode was placed in contact with the drop.

[0308] The pH changes are summarized in Table 4:

[0309] [Table 4]

[0310] The results are also summarized in FIG.

[0311] The film-forming chitosan-containing solutions showed a significant decrease in pH towards the normal pH of skin below pH 5.0 at chitosan concentrations above 0.3%. A minimum pH was reached with solutions A and B having between 1.0% and 3.0% chitosan.

[0312] The above effect was more pronounced in solution A than in solution B.

[0313] The effect was dramatically less when the same acid as solution A was used without the chitosan. Without being bound by theory, it appears that the acid in solution C passes directly into the skin and does not remain on the surface of the skin.

[0314] Example 2 Chitosan film-forming composition Skin PAMPA Skin PAMPA (Parallel Artificial Membrane Permeability Assay) was performed to test the hypothesis that the release of active agents from the chitosan film-forming composition of the present invention is altered or delayed compared to other formulations containing different polymers or no polymer at all. The permeation of lactic acid was measured using a Skin PAMPA sandwich consisting of two 96-well plates configured so that one plate is precisely placed under the plate containing the porous lipid-impregnated filter. The wells of the lower plate were filled with the acceptor solution and the wells of the upper plate were filled with the four different test formulations AD. The plates were then stacked and incubated. The Skin PAMPA model has been used to evaluate semi-solid formulations and was found to show good correlation with ex vivo permeation studies (Sinko et al., 2012; Luo et al., 2016). The release profiles from the four test formulations AD were measured at three different time points using lactic acid as a marker molecule to measure the storage capacity of the various test formulations.

[0315] The following formulations AD were tested.

[0316] [Table 5]

[0317] All percentages in the above table are w / w. The formulations were prepared by mixing the 10% potassium sorbate component with a solution of lactic acid, glycolic acid, polymer (or no polymer for formulation D) and water and stirring for 4 hours. The glycerol component containing urea and polysorbate 20 was then added and the mixture was stirred for 1 minute. In the final step, potassium sorbate and ascorbic acid were added and the solution was stirred. The pH was measured and adjusted to pH 5±0.2 with NaOH.

[0318] An acceptor phase consisting of 20 mM phosphate buffer, pH 5.0 was selected based on theoretical evaluations taking into account chemical compatibility, pH and precipitation conditions. To determine the appropriate time point for this study, Skin PAMPA experiments with formulation A in 20 mM phosphate buffer, pH 5 were analyzed at 30, 90 and 300 min. 25 μl of each sample was poured into the well of the donor compartment. Detectable amounts of lactic acid were observed in the acceptor compartment at all three time points. However, the value of lactic acid released from the test formulation at 30 min was close to the detection limit of the original analytical method. Therefore, in subsequent studies, the test time points were set at 60, 120 and 300 min, and the analytical method was adjusted to accommodate the measurement of lower concentrations of lactic acid. To obtain a preliminary impression of the evaporation time of the test formulations, 10 μl and 25 μl of formulations A and C were applied onto coated paper cards and film formation was monitored by visual inspection of the cards. As expected, film formation occurred somewhat faster with the 10 μl sample, but for both application volumes and formulations, films formed within 1 h. The evaporation behavior of the various formulations in the Skin PAMPA wells will vary depending on the hydration state of the artificial membrane. The study was performed uncapped to promote film formation from the polymer-containing formulations. Based on preliminary evaluation, 10 μl was chosen as the final sample volume for the main experiment. Due to the high viscosity of the formulations, a pipette employing positive-displacement technology was used to transfer the solutions into the wells. The pH of all formulations was recorded after preparation and adjusted to pH 5 with 30% sodium hydroxide. The sodium hydroxide was poured slowly into the formulation to avoid chemical reactions in the area where the base entered the formulation. At the end of the experiment, a shiny film was observed in all wells with the polymer-containing formulation, while the wells with the formulation without polymer, i.e., formulation D, appeared empty (presumably due to evaporation of water). Most of the film appeared dry, as indicated by the absence of the formulation aspirated when touched with the tip.

[0319] Lactic acid in the samples was measured using analytical HPLC by transferring 180 μl of each Skin PAMPA sample to an HPLC vial with a 300 μl glass HPLC tube. 20 μl of 8.5% phosphoric acid was added and mixed well. Samples were measured against standards.

[0320] Analysis conditions Instrument: Agilent HP 1100 connected to Waters Empower 3 SR3 Column: Waters Atlantis® T3 3.0x150mm, 3μm Column temperature: 30℃ Mobile phase A: 0.1% phosphoric acid aqueous solution Mobile phase B: Acetonitrile Flow rate: 0.23ml / min Injection volume: 12 μl Wavelength: 210nm

[0321] [Table 6]

[0322] Retention time Lactic acid approx. 7.2 min. Evaluation: Linear, 1 / x-weighting Analysis criteria: Percentage deviation of recalculated calibration samples: ≤ 15% Correlation coefficient r: ≧0.999 Percentage deviation of quality control samples: ≦15%

[0323] result The permeation of lactate from the four formulations AD was evaluated using Skin PAMPA at three different time points. It is assumed that the polymer affects the release rate of the selected marker. Formulation D without chitosan (and without any other polymer) was used as a standard sample. In this test, formulation D without any polymer showed significantly higher lactate values. Formulation C with Natrosol® 250HX showed higher lactate values ​​than the two formulations of the invention with chitosan, formulations A and B. Thus, the membrane tends to have lower permeation with chitosan-containing formulations. It can be considered that the release of lactate, which is predominantly negatively charged at formulation pH 5, is delayed due to interactions in the formulation with chitosan, a cationic polymer, compared to the polymer-free formulation or neutral polymer. In addition, the diffusion rate of the dissolved active substance can also be influenced by the viscosity of the formulation, which was not the subject of this study. The ranking of the various formulations (D>C>A>B) was the same at all time points tested, but the permeation amount increased from each earlier time point. Between 60 and 120 min (within 1 h), a rapid increase in permeation was observed for all samples, but over the next 180 min, only a gradual increase was observed. Each time point was performed on a separate Skin PAMPA plate, demonstrating the reproducibility of the study. The standard deviation of this experiment is comparable to that reported in the literature (Sinko et al., 2014).

[0324] Example 3. Determining the effect of chitosan film-forming compositions on the microorganisms of the human skin core microbiome Although the microbiome varies from person to person, the core microbiome contains several key microorganisms including Staphylococcus epidermidis, Staphylococcus mitis, Staphylococcus capitis, Corynebacterium specs., Propionibacterium acnes, Malassezia pachydermatis, and Streptococcus spec., among others.

[0325] For this experiment, the microbiome microorganisms are seeded on an agar plate. The microorganisms are then embedded in a special microbiome agar matrix to simulate the epidermis layer. The surface is then contaminated with Staphylococcus aureus as a representative pathogenic microorganism. Staphylococcus aureus does not belong to the normal human skin microbiome. In the next step, the test formulation is applied to a small area on the surface and the test setup is incubated overnight at 37°C. After incubation, the growth of the microbiome microorganisms embedded in the matrix and Staphylococcus aureus on the surface is used to evaluate the effect of the test formulation on the microbiome microorganisms. If the applied test formulation is able to reduce or inhibit the growth of Staphylococcus aureus while maintaining or promoting the growth of the microbiome microorganisms underneath, the test formulation exhibits good surface protection properties without adversely affecting the skin microbiome. If the applied product also causes growth inhibition of microbiome microorganisms, the product is evaluated as having a negative impact on the human microbiome. A disinfectant (isopropanol:water 70:30) is used as a negative control to inhibit the growth of pathogens as well as microbiome microorganisms. A buffer solution (for dilution during application; 0.9% (w / w) NaCl aqueous solution) is used as a negative control. The sample volume of the test formulation is 20 μl. The inoculation microbiome is 2.0 x 10 6 CFU (colony forming units). The inoculum pathogen was 2.0x10 6 CFU.

[0326] The following formulations EF were tested: [Table 7]

[0327] All percentages in the above table are w / w. Formulations E and G are intended as gels, and Formulation F is intended as a spray.

[0328] result As can be seen from Figure 3 (Test Formulation E), Figure 4 (Test Formulation F) and Figure 5 (Test Formulation G), Test Formulations E-F provided good surface protection by inhibiting the growth of pathogenic Staphylococcus aureus strains, while the underlying microbiome microorganisms were not adversely affected by the surface treatment. The negative controls in Figures 3, 4 and 5 show growth on the surface, i.e., growth of Staphylococcus aureus. The positive controls in Figures 3, 4 and 5 show no growth on the surface or growth of underlying microbiome microorganisms.

[0329] Example 4: Determination of antimicrobial efficacy kinetics of liquid compositions with chitosan and the effect of liquid compositions with chitosan and disinfection on regrowth in human skin 1. Test Method The antimicrobial kinetics test is based on the European Pharmacopoeia test method "Efficacy of antimicrobial preservation" and provides a visual and semi-quantitative overview of the antimicrobial effectiveness of an antimicrobial sample compared to an untreated standard sample at a given time.

[0330] 2. Test Description For this purpose, a sample (approximately 3x3cm to 5x5cm) or 0.5-1.0 ml of test solution is spiked with a defined number of bacteria and incubated under standard conditions for a defined time. Time point t0 is used to indicate the initial contamination. At the end of the incubation time, surviving microorganisms are recovered from the sample and a dilution series is plated on agar plates. The agar plates are incubated at 37°C for 18-24 hours and the number of colony forming units (CFU) is counted.

[0331] 3. Test parameters of the tests performed The test bacteria corresponded to the endogenous skin flora. The sample materials were the test formulation E of Example 3 as well as a disinfectant solution (70% isopropanol). The sample size was approximately 50 cm 2 and a sample volume of 100 μl. The contact times were 0, 1 h, 2 h, 4 h, 6 h, post-contact, and 1 h post-contact.

[0332] 4. Remarks regarding test materials, test conduct and results: Rodac contact plates were used to collect microorganisms from human skin (upper arm) before and after treatment. The upper arm was chosen to avoid contamination by touch or clothing. Disinfection was performed with 70% isopropanol.

[0333] 5. References: European Pharmacopoeia: 5.1.3. Efficacy of antimicrobial preservation.

[0334] 6. Results The results are shown in Figure 6. The upper arm test area was disinfected and air-dried for 2 minutes. For "Formulation E", Formulation E was applied to the test area and air-dried. Time t0 was taken after disinfection and application and drying of Formulation E. After the defined time points, bacteria were collected from the test area by Rodac contact plates. The small white and yellowish colonies are typical Staphylococci species from the human skin microbiome. The yellow-orange colonies are Staphylococcus aureus, which does not belong to the normal skin microbiome. This Staphylococcus aureus was found only in the "disinfectant" test area, but not in the "Formulation E" test area.

[0335] Further results are shown in Figure 7. After a test time of 6 h, the test area was exposed to clothing for 10 min, resulting in a typical transfer of microorganisms from the clothing to the skin surface (time point immediately after contact). 1 h after removing the clothing, bacteria were collected from the test area by means of a Rodac contact plate. Sample "Formulation E" showed typical superficial microorganisms of the skin flora. Sample "Disinfectant" also showed pathogenic microorganisms that do not belong to the normal commensal and healthy skin flora (gram-negative bacteria = large colonies).

[0336] Overall, the results indicate that the chitosan-containing composition of the present invention inhibits the growth of pathogenic microbial taxa such as Staphylococcus aureus. The chitosan-containing composition of the present invention appears to differentially promote the growth of beneficial versus pathogenic microbial taxa and inhibits pathogenic microorganisms from colonizing previously disinfected areas. Disinfection kills microorganisms on the "tested skin", but leaves the area unprotected, allowing both beneficial and pathogenic microorganisms to colonize, leading to an unhealthy microbiome and even dysbiosis. Without being bound by scientific theory, it may be hypothesized at present that the above significant effects of Formulation E on the microbiome are specifically associated with the corresponding pH changes, as can be seen in Figure 1 for "ΔpH Ch-Lac / Gly".

[0337] Example 5: Determination of the antibacterial effect kinetics of a liquid composition containing chitosan and the effect of a liquid composition containing chitosan and disinfection on regrowth in human skin The efficacy of Formulation E (described in Example 3) was further tested in a campaign with 300 volunteer testers. Each tester received a pack of Formulation E and was then able to provide feedback via a corresponding website within 2-4 weeks. The evaluation was also provided on the website. No personal interviews with the test subjects were conducted. The results of the evaluation for chafing, pimples, cracks or chapping (or fissures), insect bites, blisters, scar care and stinging lips are shown in Figures 8 and 9. As can be seen from Figures 8 and 9, according to the registered testers, the test Formulation E has a very good effect on all of the above indications. The testers would highly prefer and / or recommend Formulation E for the treatment or care of chafing, pimples, cracks or chapping (or fissures), insect bites, blisters, scar care and stinging lips (Figure 8). Furthermore, according to the tester, formulation E shows very significant effectiveness in treating chafing, pimples, cracked or chapped skin (or fissures), insect bites, blisters, scar care and stinging lips (Figure 9).

Claims

1. Use of a liquid cosmetic composition having chitosan to differentially promote the growth of microbiota in the ectodermal tissue of a subject.

2. The use according to claim 1 , wherein the liquid cosmetic composition is applied topically to form a cosmetic film.

3. The use according to claim 2, wherein the formed film has a thickness of from 0.001 nm to 50 μm, preferably from 0.001 nm to 10 μm, more preferably from 0.001 nm to 1 μm.

4. The use according to any one of claims 1 to 3, wherein the film-forming liquid cosmetic composition differentially promotes the growth of one or more microbial taxa relative to another microbial taxa.

5. The use according to claim 4, wherein the film-forming liquid cosmetic composition differentially promotes the growth of one or more beneficial microbial taxa relative to one or more pathogenic microbial taxa.

6. 6. The use according to claim 5, wherein the at least one beneficial taxon comprises Staphylococcus epidermidis, Staphylococcus mitis, Staphylococcus capitis, Corynebacterium specs., Propionibacterium acnes, Malassezia pachydermatis, Streptococcus spec., Streptococcus spec., Lactobacillus spec., Micrococcus spec. and Bacillus spec.

7. 6. The use according to claim 5, wherein the at least one pathogenic taxon comprises Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Enterococcus faecalis / faecium, E. coli, Klebsiella pneumoniae, Candida albicans, Microsporum canis, Acinetobacter baumanii, Staphylococcus intermedius and Staphylococcus pseudointermedius.

8. 8. The use according to any one of claims 1 to 7, wherein said chitosan has a degree of acetylation of 15% or less, more preferably 10% or less, even more preferably 5% or less or even more preferably 2.5% or less.

9. The use according to any one of claims 1 to 8, wherein the liquid cosmetic composition comprises one further cosmetic agent.

10. 10. The use according to claim 9, wherein the one additional cosmetic agent is selected from the group comprising urea, glycolic acid, glyoxylic acid, glycerol, pentylene glycol, lactic acid, ascorbic acid, pyroglutamic acid, citric acid, tartaric acid, fumaric acid, succinic acid, malic acid, mandelic acid, aloe vera, rosa gallica, hyaluronic acid, salicylic acid, gallic acid, cellulose and its derivatives, pectin and its derivatives, gum arabic, dextrin, cyclodextrin, xanthan gum, thiocyanates, amino acids, sorbic acid, sodium chloride or combinations thereof.

11. The use according to claim 9 or 10, wherein the at least one further cosmetic agent comprises glycolic acid and / or lactic acid.

12. The composition comprises, relative to the total weight of the liquid cosmetic composition: 0.010 to 4.0% (w / w) chitosan, 0.005 to 2.5% (w / w) glycolic acid, 0.005 to 2.5% (w / w) lactic acid, The use according to any one of claims 9 to 11, having the formula:

13. The use according to any one of claims 1 to 12, wherein the liquid cosmetic composition comprises a disinfectant.

14. 14. The use according to claim 13, wherein the disinfectant comprises an alcohol, an aldehyde, iodine, chlorine, a quaternary ammonia compound, a peroxide, an amphoteric surfactant, a phenol, an alkylamine, an acid and / or a base.

15. The use according to any one of claims 1 to 14, wherein the ectodermal tissue is skin.

16. The use according to claim 15, wherein the ectodermal tissue is the epidermis.

17. 17. The use according to claim 16, wherein the epidermis is damaged epidermis, said damage comprising sunburn, acne, cuts, abrasions, incisions, pimples, blisters, puncture wounds, burns, aging, rashes, irradiated skin, laser treated skin, plasma treated skin, tattoos, tattoo removal, skin peeling, scar tissue, dry skin, oily skin, cracks, stretch marks or wrinkles.

18. 17. The use according to claim 16, wherein the epidermis is a stressed epidermis, said stress being caused by a prosthesis, an endoprosthesis, an orthosis, a reinforced exoskeleton, a bandage, a pressure dressing, a stocking, a bandage, a latex protective material, a massager, a ventilation mask, an anti-apnea measure, work or protective clothing, gloves, a pacifier, tight clothing or shoes, a disinfectant, a cosmetic treatment, a cosmetic product, a preservative, a cleaning agent, sweat, lack of personal hygiene, lying or sitting for long periods of time, a wound dressing, a sunburn, a burn, a puncture wound, irradiation, laser treatment, plasma treatment, getting a tattoo and / or removing a tattoo.

19. 19. The use according to claim 18, wherein the stress is caused by a prosthesis, an endoprosthesis, a brace, a reinforced exoskeleton, a bandage, a pressure bandage, a stocking, a dressing, a latex protective material, a massager, a ventilation mask, work or protective clothing, gloves, a pacifier, tight clothing or shoes, lying or sitting for long periods of time, or a wound dressing.

20. The use according to any one of claims 1 to 19, wherein the ectodermal tissue, skin, epidermis, damaged or stressed epidermis of the subject has been previously sterilized or disinfected.

21. a) chitosan or a salt thereof, the degree of acetylation of which is 20% or less; and b) at least one further cosmetic agent; A liquid cosmetic composition comprising: A liquid cosmetic composition, wherein the pH of said liquid cosmetic composition is from about 4.0 to about 6.5; and said at least one additional cosmetic agent comprises glycolic acid and lactic acid.

22. 22. The liquid cosmetic composition according to claim 21, wherein the degree of acetylation of chitosan is 15% or less, more preferably 10% or less, even more preferably 5% or less, or even more preferably 2.5% or less.

23. The composition comprises, relative to the total weight of the liquid cosmetic composition: 0.010 to 4.0% (w / w) chitosan, 0.005 to 2.5% (w / w) glycolic acid, 0.005 to 2.5% (w / w) lactic acid, 22. The liquid cosmetic composition according to claim 20 or 21, having the formula:

24. A kit comprising a liquid cosmetic composition according to any one of claims 21 to 23, further comprising a disinfectant, preferably selected from the group comprising alcohols, aldehydes, iodine, chlorine, quaternary ammonia compounds, peroxides, amphoteric surfactants, phenols, alkylamines, acids and / or bases.

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