Oral care compositions

Abstract

The present invention relates to novel oral care compositions and their uses.

Description

[Background technology]

[0001] background The oral epithelial barrier (including the gingival epithelial barrier) separates the host from the environment and provides a first line of defense against pathogens, exogenous substances, and mechanical stress. Disruption of the gingival epithelial barrier and subsequent invasion of host tissues by exogenous pathogens induces an inflammatory response and establishes chronic infection.

[0002] Aligner splint therapy is a treatment concept for orthodontally harmonizing dental arches by wearing removable dental splints for several hours. These aligner splints are individually adapted to the user's dentition and cover both the user's teeth and a portion of the user's gums. Wearing aligner splints for extended periods of time poses the risk of gum irritation, gum recession, and bacterial overgrowth between the aligner splint and the covered tooth and gum surfaces. Aligner splint users often complain of bad breath and dry mouth in the morning after wearing the aligners overnight.

[0003] Cosmetic oral hygiene products such as toothpaste, mouthwash, or mouth rinses are typically "rinse-off products," meaning they only work for a short period of time and are therefore not suitable for the problems that arise during the wearing of aligner splints.

[0004] EP 3 220 875 (Patent Document 1) describes a toothpaste containing high levels of natural calcium carbonate, sodium chloride, and an antibacterial amount of zinc salt. However, this care composition is not suitable for resolving problems associated with wearing aligner splints. EP 1 888 014 (Patent Document 2) describes a dental care composition for improving tooth mineralization. This category includes the commercially available MI Paste Plus. WO 2021 168684 (Patent Document 3) describes oral care compositions that do not contain jasmonic acid, gibberellic acid, and / or zeatin compounds. These oral care compositions are not similar to the oral care composition of the present invention and are not suitable for alleviating problems experienced by aligner wearers. US 2007 / 0003502 (Patent Document 4) focuses on the use of compositions containing at least 5% maltose or trehalose. Although hair tonics, bath salts, and beauty creams, as well as mouthwashes and toothpastes (Examples 48-50), are disclosed, the examples either contain no hyaluronic acid or only 0.1% hyaluronic acid. US 2020 / 0390676 (Patent Document 5) focuses on oral care compositions containing hyaluronic acid with a specific viscosity based on the amount of hyaluronic acid and, optionally, an additional polymer. Although the document discloses various oral care compositions, none of them contain more than 2% xylitol. Furthermore, there is no teaching on the use of additional anti-inflammatory substances or catechins. KR1020000031162 (Patent Document 6) refers to oral compositions containing triclosan and hyaluronic acid, but the application does not disclose or suggest the composition according to the present invention. Furthermore, triclosan can cause contact dermatitis, i.e. skin irritation and increased allergic reactions, and is a potential endocrine disruptor; for example, triclosan is due to be banned in mouthwashes in the European Union in 2023 (see coslaw.eu).Moreover, the examples in KR1020000031162 (Patent Document 6) are not suitable as compositions according to the present invention, that is, the application does not provide a person skilled in the art with the knowledge to arrive at compositions according to the present invention.

[0005] There is a need for oral care compositions that can counteract these risks and produce an improved mouth feel. The present invention relates to oral care compositions that have improved care potential compared to conventional oral care compositions due to the specific combination of different care components and a longer exposure time (inhibiting biofilm formation (usually bacteria and their metabolic products), preventing and healing inflammation, and assisting in the regeneration of damaged tissue). It is even possible to simply obtain the individual components from renewable (biological) raw materials. The care or preventive substances in such oral care compositions and the care compositions should preferably be easy to handle and can be used outside of a dental clinic. The primary care and supportive roles are achieved through application of the oral care composition according to the present invention to the mouth. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] EP 3 220 875 [Patent Document 2] EP 1 888 014 [Patent Document 3] WO 2021 168684 [Patent Document 4] US 2007 / 0003502 [Patent Document 5] US 2020 / 0390676 [Patent Document 6] KR1020000031162 Summary of the Invention

[0007] definition The term "a" as used herein generally refers to an indefinite article and means "one or more than one," e.g., 1, 2, 3, etc. When the term "a" refers to only a single item, this will either be clear from the context or will be explicitly written in the form "a(1)."

[0008] The term "abrasive" refers to solid particles typically present in oral care compositions such as toothpaste. Well-known abrasives for oral compositions include calcium-containing abrasives, silica abrasives, carbonate abrasives, phosphate abrasives, alumina abrasives, and other suitable abrasives. Non-limiting examples include calcium carbonate, dicalcium phosphate, tricalcium phosphate, calcium orthophosphate, calcium metaphosphate, calcium polyphosphate, calcium hydroxyapatite, calcium carbonate, strontium carbonate, calcium phosphate, sodium hexametaphosphate, dicalcium phosphate, tricalcium phosphate, calcium orthophosphate, calcium metaphosphate, fused silica, fumed silica, precipitated silica, hydrous silica, diatomaceous earth, barium sulfate, wollastonite, perlite, alumina (Al2O3), polymethyl methacrylate particles, Tospearl, and combinations of any of the foregoing. Abrasives, such as silica abrasives, may have an average particle size ranging from 0.05 to 30 μm. Abrasives are commercially available, for example silicas bearing the name "Syloid" or Zeodent®, especially Zeodent® 119, Zeodent® 118, Zeodent® 109, and Zeodent® 129.

[0009] An "additional component" is any compound known as of the filing date of this application that can be used in oral care compositions. Those of greatest interest are listed in group (e) and can be categorized or described according to their cosmetic and / or therapeutic benefits or their postulated mechanisms of action or functions. However, it should be understood that additional compounds may, in some cases, provide more than one cosmetic and / or therapeutic benefit or effect through more than one mechanism of action or function. Thus, the classification in (e) herein is made for convenience and is not intended to limit any component to the specifically listed function or activity. The term "additional component" also includes compounds found in extracts and oils in addition to components from groups (a)-(d). Precise characterization of these components is not required, but the total amount of these components is required. This can be calculated by simply subtracting the amounts of components from groups (a)-(d) from the amount of extract or oil used. In other words, the compounds in groups (a) to (d) or (e) may have other beneficial effects in addition to those of their respective classes. For example, glycerol or ethylene glycol are the main polar solvents, but they also have a humectant effect. Nevertheless, they are not mentioned as humectants in group (e), but are already counted in group (a) for the purpose of estimating the amount of various compounds in the compositions of the present invention. Tea-derived catechins may have antioxidant and vasodilator effects, but they are naturally counted only once when determining the amount of additional component (e) in the formulation.

[0010] "Allantoin" (5-ureidohydantoin) is an oxidation product of uric acid. Allantoin helps with wounds and skin irritation and stimulates the growth of healthy tissue.

[0011] As used herein, "carbomer" refers to synthetically produced polyacrylic acid (PAA), typically crosslinked with a polyalkene ether of a sugar or polyalcohol. These can be homopolymers of acrylic acid crosslinked with allyl ethers of pentaerythritol, sucrose, or propylene. Polyacrylic acid is found with various degrees of polymerization. Depending on the degree of polymerization (molecular weight), carbomer gels vary in viscosity and therefore in their cosmetic, pharmaceutical, and technical applications. In aqueous solutions at neutral pH, PAA is an anionic polymer; that is, many of the PA side chains have lost their protons and become negatively charged. This gives PAA-polyelectrolytes the ability to absorb and retain water, allowing them to expand to many times their original volume. High-molecular-weight crosslinked polyacrylic acids are also known by the trade name Carbomer. Well-known trade names include Carbopol®, Pemulen®, and Noveon®. They are mainly polymers of acrylic acid crosslinked with polyalkenyl ethers or divinyl glycol. The number after the name defines the composite of the molar volume and viscosity of a 2% solution at 20°C in mPa*s. According to the USP (United States Pharmacopeia), three types of carbomers are generally classified, which can be distinguished by their pharmaceutically relevant viscosity: Type A (4 to 11 Pa*s) (e.g., Carbopol 981, Carbopol 971, or Carbopol 71G), Type B (25-45 Pa*s (e.g., Carbopol 974P, Carbopol 984, Carbopol 5984), and Type C (40-60 Pa*s) (e.g., Carbopol 980), Commonly used carbomers are Carbomer 50,000 (e.g., used in Carbopol 940) and Carbomer 35000 (e.g., used in Carbopol 974P and Carbomergel pH 6.5 NRF p.43).2+ , Al 3+ The presence of polyvalent cations can lead to liquefaction or flocculation of the gel. In such cases, complexation with polyvalent cations, for example with sodium edetate (NaEDTA), has a stabilizing effect.

[0012] "Catechins," as used herein, are polyphenolic plant metabolites from the flavonoid group and are therefore generally classified as secondary plant substances. They are derived from flavan-3-ols. TIFF2025529924000001.tif26128

[0013] The four most important catechins are catechin, epicatechin (each with the molecular formula C 15 H 14 O6), gallocatechin, and epigallocatechin (each with the molecular formula C 15 H 14 (having O7). TIFF2025529924000002.tif76128

[0014] Each of these substances is found in two isomeric forms: for example, (+)-catechin (C) (CAS 154-23-4) has a 2R,3S configuration, while (-)-catechin (CAS 18829-70-4) has a 2S,3R configuration.

[0015] The term catechin also encompasses esters of C, EC, GC, and EGC (e.g., with gallic acid or with 4-fatty acid ethers of gallic acid, such as 4-palmitoyl-gallic acid). For example, epigallocatechin gallate (EGCG) - epigallocatechin-3-gallate) is an ester of epigallocatechin with gallic acid.

[0016] Catechins found in green tea include, for example, EC, EC gallate (ECG), EGC, and EGC gallate (EGCG). Although the amount may vary slightly depending on the tea variety, the total amount of these four catechins in green tea leaves is generally 30% to 40% based on the dry weight of the green tea leaves. The ratio of the four catechins in green tea, EC, ECG, EGC, and EGCG, is approximately 5:10:15:30. TIFF2025529924000003.tif98128

[0017] As used herein, the term "compatible" means that the components of the composition are capable of being mixed together without interfering in a way that significantly reduces the stability and / or effectiveness of the composition.

[0018] The term "flavonoid" refers to polyphenolic secondary metabolites found in plants. They have antioxidant properties and are nutritionally important. They are generally derived from 2-phenyl-1,4-benzopyrone. The term "flavonoid" also encompasses isoflavonoids (derived from 3-phenyl-1,4-benzopyrone) and neoflavonoids (derived from 4-phenyl-1,2-benzopyrone). All three flavonoid classes are ketone-containing compounds and are therefore anthoxanthins (flavones and flavonols). Those skilled in the art will recognize which compounds fall under the term flavonoid as of the filing date of this application.

[0019] "Gibberellic acid" includes the class of compounds also known as gibberellins, which are plant hormones and tetracyclic diterpenoid acids.

[0020] The term "gum care" refers to benefits intended to relieve one or more symptoms of earlier stages of gum disease (i.e., gingivitis), including relief of red, swollen, tender gums and / or gingivitis.

[0021] The term "gum health" as used herein refers to the inherently promoting benefits of oral care compositions to provide "gum health" benefits including at least improvements in gingival and periodontal wound healing, as well as improved resilience and enhanced bacterial resorption, including early damage to periodontitis.

[0022] "Humectants" function to prevent the oral care composition from hardening upon exposure to air, to provide a moist mouthfeel, and, in certain humectants, to impart a desirable sweet taste. Humectants suitable for the present invention include edible polyhydric alcohols such as glycerin, sorbitol, erythritol, butylene glycol, polyethylene glycol, and combinations thereof.

[0023] As used herein, "hyaluronic acid" (HA) is a glycosaminoglycan. As used herein, the term "HA" also includes salts of HA, such as sodium (Na), lithium (Li), or potassium (K) salts of HA, and magnesium (Mg) or calcium (Ca) salts of HA. As used herein, the term "hyaluronic acid" also includes thiolated HA, such as HA-cysteine ​​ethyl ester conjugates (see, for example, Kafedjiiski et al., Int. J. Pharm., 343, (2007) 48-58), and salts thereof, such as alkali metal salts and alkaline earth metal salts. HA is found as a macromolecular chain of disaccharides composed of D-glucuronic acid and N-acetyl-D-glucosamine. The disaccharides are linked by a β(1→4) glycosidic bond. The term HA as used herein refers to a chain typically composed of about 250 (about 95 kDa) to about 50,000 (about 18,966 kDa) repeating disaccharide units (n=about 250 to about 50,000). The term "hyaluronic acid" encompasses fragments of hyaluronic acid typically found in hyaluronic acid chains, including those from TIFF2025529924000004.tif35128, up to the D-glucuronic acid N-acetyl-D-glucosamine disaccharide, in which glucuronic acid is linked to N-acetyl-D-glucosamine via a β(1→3) glycosidic linkage. Such fragments typically have molecular weights between 5 kDa and 150 kDa (fragments with molecular weights between 5 kDa and 130 kDa are preferred for use in cosmetics). The term "hyaluronic acid" also includes cross-linked (cross-linked) hyaluronic acid. There are widespread examples of modified HA polymers that can form either covalently or physically cross-linked biomaterials and are frequently used in cosmetics. Common methods for cross-linking hyaluronic acid are known to those skilled in the art; for example, the most established method is to use BDDE (butanediol diglycidyl ether) as a cross-linker (de Boulle et al., Dermatol Surg 2013;39:1758-1766), although other cross-linkers are also used to provide cross-linked HA, such as 1,4-butanediol or di-(propane-2,3-diol) ether cross-links. HA-hydrogels based on dynamic covalent coupling (DCC) chemistry are also used.

[0024] As used herein, a "hydrogel" is a gel of water (film-forming agent) and a water-insoluble polymer capable of binding / containing water. The molecules that form the gel are chemically linked, e.g., by covalent or ionic bonds, or physically, e.g., by entanglement of polymer chains, to form a network. That is, a hydrogel refers to a composition having a substantially dilute crosslinked system that does not flow at steady state, although a liquid phase can still diffuse through the system. By weight, gels are primarily liquid, but they behave like solids due to the three-dimensional crosslinked network within the liquid. It is the crosslinks within the fluid that give the gel its structure (rigidity) and contribute to its adhesive stickiness. Incorporated hydrophilic polymer components swell in water, significantly increasing their volume, without losing their material cohesion. Hydrogels can contain other protic solvents in addition to water.

[0025] When a range is given (eg, between value A and value B), value A and value B are within the range.

[0026] As used herein, "jasmonic acid compounds" include jasmonic acid and jasmonic acid derivatives available to those skilled in the art, including jasmonic acid, dihydrojasmonic acid, hydroxyjasmonic acid, dihydrohydroxyjasmonic acid, methyl jasmonate, and isomers thereof.

[0027] The term "lotus" as used herein is interchangeable and refers to the lotus flower (nelumbo). There are two species of nelumbo: Nelumbo nucifera Gaertn. (Asian lotus) and Nelumbo lutea Pear (American lotus). The roots, fruits, seeds, and stems of all known lotus species are edible. Lotus extracts contain many medicinally useful compounds, such as flavonoids, phenolic acids, alkaloids, antioxidants, and vitamin C. Extraction methods for various tissues of lotus are well known to those skilled in the art (e.g., Lin et al., "The Latest Studies on Lotus (Nelumbo nucifera) - an Emerging Horticultural Model Plant", Int J Mol Sci 2019, 20, 3680, 1-13; Chen et al. "Simultaneous Analysis of Anthocyanin and Non-Anthocyanin Flavonoids in Various Tissues of Different Lotus (Nelumbo) Cultivars by HPLC-DAD-ESI-MS"). n ” PLOSone 2013, Vol. 8, Issue 4, 1-13).

[0028] As used herein, "lotus (root) extract" refers to an aqueous extract, or an extract with other protic solvents, preferably lower alcohols (such as ethanol), derived primarily from tissues of the lotus plant, such as the roots, petals, stems, seeds, and / or leaves, or a mixture of aqueous extract and additional protic solvent extract. The content of additional protic solvent can be from 0% (aqueous extract) to up to 100% of the additional protic solvent. Usually, the extract is (freeze) dried after extraction.

[0029] "Mannan" is a polysaccharide. Plant mannans are linear polymers of primarily mannose. The mannose units range from being predominantly β(1-4) linked to being exclusively β(1-4) linked. Galactomannans occasionally exhibit α(1-6) branching with galactose. Glucomannans have a mixed β(1-4) backbone of mannose / glucose. Galactoglucomannans have a mixed β(1-4) backbone of mannose / glucose, occasionally containing α(1-6) branching with galactose. Yeast mannans typically exhibit an α(1-6) backbone with α(1-2) and α(1-3) branching with glucose. Galactomannans come from a variety of sources. A plant source of linear (1-4)-β-D-manno-pyranose branched by (1-6) linkages with α-D-galactopyranose units in an approximate 3:1 ratio (around 75% mannose units and around 25% galactose units) is Caesalpinia spinosa gum. Other plant sources of galactomannans, possibly with different ratios of mannose to galactose, are Cyamopsis tetragonoloba (guar) or Ceratonia siliqua (carob tree).

[0030] The term "oral enhancing polyol" can be a sugar alcohol, a disaccharide, a polysaccharide, and preferably a non-reducing sugar. The sugar alcohol has the formula (CHOH) nNon-reducing sugars belong to the class of polyols obtainable by hydrogenation of sugar compounds having H2, where higher values ​​exist, such as isomalt, maltitol, lactitol, maltotetratol, polyglycitol, or combinations thereof. Preferably, n ranges from 7 (inclusive) to 12 (inclusive). Non-reducing sugars belong to the class of saccharides that do not form compounds with aldehyde or ketone functional groups. Non-reducing sugars are stable in water and do not react with weak oxidizing substances to produce sugar alcohols. Non-reducing sugars cannot donate electrons to other molecules and are typically disaccharides, trisaccharides, tetrasaccharides, pentasaccharides, or combinations thereof, such as sucrose, trehalose, raffinose, stachyose, and verbascose.

[0031] "Oral care composition" as used herein means a product that is retained in the oral cavity for a period of time sufficient to contact the tooth surfaces or oral tissues.

[0032] The word "or," when used in conjunction with two or more elements, means that the elements can be found individually as well as in combination with each other; for example, "gums or teeth" does not exclude the combination "gums and teeth," i.e., the term includes "gums only," "teeth only," or "gums and teeth."

[0033] The term "orally acceptable carrier substance" includes one or more acceptable solid or liquid excipients or diluents that are suitable for use in the oral cavity.

[0034] As used herein, the term "promoting" means promoting and / or enhancing the gum health benefits associated with application of the oral care composition of the present invention to the oral cavity.

[0035] The term "protic solvent" is known to those skilled in the art. In the context of the present invention, it refers to a solvent that has a hydrogen atom bonded to an oxygen, nitrogen, or fluoride and is in the liquid phase at standard ambient temperature and pressure (T=298.15 K and p=1013 hPa). Non-limiting examples are (other than water) short-chain monohydric or polyhydric alcohols (e.g., methanol, ethanol, 1-propanol, 2-propanol, 1,2-propanediol (propylene glycol), (propane-1,2,3-triol) (glycerol), 1-butanol, etc.), short-chain primary and secondary amines, short-chain primary and secondary amides (e.g., formamide), and also pyridine 3-carboxamide, and polysorbates (e.g., TWEEN 20 (polyethylene glycol-sorbitan-monolaurate), TWEEN 40 polyoxyethylene-sorbitan-monopalmitate, and TWEEN 80 (polyethylene glycol-sorbitan-monooleate)).

[0036] "Short chain" as used herein refers to a compound having a chain of 1, 2, 3, 4, 5, or 6 carbon atoms. Such a chain can be branched and can form a ring, and it can be substituted with one or more functional groups (e.g., -OH for alcohols, COOH for organic acids, -NH for amines, C(O)NH for amides).

[0037] As used herein, the term "strip" includes a material whose (1) length in its longest dimension is generally greater than its width and whose (2) width is generally greater than its thickness. The strip can be rectangular, curved, curvilinear, semicircular, with rounded corners, with cut slits, with cut notches, bent into a three-dimensional shape, or a combination thereof. The strip can be solid, semi-rigid, textured, malleable, flexible, deformable, permanently deformable, or a combination thereof. The strip can be made from a sheet of plastic, including polyethylene, or a sheet of wax.

[0038] As used herein, the term "substantially free" refers to a composition in which the specified substance is present at less than 0.001% (w / w) of the specified substance. The term also includes compositions in which the specified substance is present only as an impurity among other intentionally added substances.

[0039] The terms "essentially free" and "free" refer to the presence of less than 0.0001% (w / w) of the specified substance in a composition.

[0040] The term "free" means that the indicated substance is not present in the composition at analytically detectable levels.

[0041] The term "tooth" as used herein refers to both natural and artificial teeth and includes one tooth or multiple teeth.

[0042] The term "tooth surface" as used herein refers to both natural tooth surfaces and artificial tooth or denture surfaces.

[0043] The terms "total water" or "total solvent" as used herein refer to both free water and water bound by other ingredients in the oral care composition, or both free solvent and solvent bound by other ingredients in the oral care composition, for example, by mucoadhesive polymers in hydrogels.

[0044] As used herein, a "water-insoluble polymer" is capable of forming a (hydro)gel with water and / or other solvents. A water-insoluble polymer is barely soluble or not soluble at all in water at 25°C. In this context, "barely" means that up to 10% of the polymer can be dissolved in water at 25°C without heating the water and / or the polymer. Non-limiting examples include gelatin (a mixture of animal protein and collagen), (cross-linked) poly(meth)acrylates such as (cross-linked) polyacrylic acid, (cross-linked) polyurethane polymers, (trimethylated) hyaluronic acid, povidone-iodine, and polysaccharides and their derivatives, such as mannan, glycogen, starch, alginate, pectin, chitin, chitosan (deacetylated chitin), and cellulose and its derivatives. Cellulose derivatives with mucoadhesive properties are mostly (cross-linked) sodium carboxymethylcellulose, hydroxyethylcellulose, ethylcellulose, methylcellulose, and hydroxypropylmethylcellulose. Crosslinking of poly(meth)acrylates during polymerization by adding to them compounds with at least two vinyl substructures, such as divinyl glycol or pentaerythritol allyl ether.

[0045] A "vasodilatory component" produces a physiological response that increases the cross-sectional area of ​​blood vessels, thereby increasing blood flow behind the affected vascular segment.

[0046] "Viscosity," as used herein, is the property of a liquid to resist displacement of two adjacent layers relative to one another. Viscosity is expressed in Pascal-seconds. The viscosity of compositions according to the present invention can be determined by a rotational rheometer equipped with a 4° / 40 mm diameter cone-plate with a standard smooth surface (usually a stainless steel surface).

[0047] The "yield point" in viscosity refers to the resistance to initial flow of a fluid, or in other words, the stress required to initiate fluid movement.

[0048] "Zeatin compounds" as used herein include cis and trans isomers of zeatin and cis and trans isomers of zeatin derivatives available to one of ordinary skill in the art.

[0049] Unless otherwise stated, percentages are expressed as percentages by weight (%(w / w)). Unless otherwise indicated, weight percentages (%(w / w)) and ratios are based on the weight of the total composition. All component percentages, ratios and amounts described herein are based on the actual amount of the target compound, and do not include solvents, fillers or other materials that may be combined with the component as a commercial product, unless otherwise noted.

[0050] The term "comprising" when used in conjunction with a subject matter herein means that other subject matters are also included / may be present. The term "comprising" also includes, as one preferred option, an embodiment "consisting of." For example, a composition comprising components (a) to (d) may also have additional components. However, this term also encompasses a preferred embodiment in which the composition consists of components (a) to (d), i.e., no additional components are present. Thus, when the term "comprising" is used herein, it is always possible to limit a subject matter comprising an essential subject matter and an additional subject matter to an embodiment in which the subject matter consists of the essential subject matter (and no additional subject matter can be added).

[0051] Those skilled in the art will understand that any two or more aspects of the present invention, regardless of the fact that they are aspects, preferred aspects, more preferred aspects, etc., can be combined with each other (unless such combination is contrary to the laws of nature or is expressly excluded). [Brief explanation of the drawings]

[0052] DETAILED DESCRIPTION OF THE INVENTION

[0053] Detailed Description of the Invention The oral care compositions described in this invention are designed for application to the gum tissue, as well as other soft tissues (e.g., buccal mucosa) and teeth in a user's oral cavity, and for application to a user's aligner splint.

[0054] It has been surprisingly found that the oral care composition of the present invention, preferably with an optimal viscosity, provides the user with better sensory benefits and is particularly useful for promoting gum health.It has been surprisingly found that the oral care composition according to the present invention, with an optimal viscosity resulting from the combination of HA and preferably a second water-insoluble polymer with an anti-inflammatory component and preferably a further protective component, such as an antioxidant, preferably from the group of catechins, is particularly suitable for significantly improving the gum health and oral sensation (taste in the mouth, sensitivity, bad breath, and dry mouth) of aligner splint wearers during the period of correction of tooth position.

[0055] A first aspect of the present invention is (a) at least one protic solvent, wherein the at least one protic solvent is water, and wherein the total amount of all protic solvents is 45% (w / w) to 85% (w / w), and the amount of water is at least 45% (w / w); (b) at least one water-insoluble polymer, wherein the at least one water-insoluble polymer is hyaluronic acid, and wherein the total amount of all water-insoluble polymers is 0.4% (w / w) to 5% (w / w), preferably 0.8% (w / w) to 5% (w / w), and wherein the amount of hyaluronic acid is at least 0.4% (w / w), preferably at least 0.8% (w / w), more preferably 0.9% (w / w) to 5% (w / w), and wherein the amount of hyaluronic acid is at least 0.8% (w / w); (c) one or more sugar alcohols (polyols) selected from the group consisting of sorbitol, xylitol, and erythritol, wherein the total amount of polyols (selected from the group consisting of sorbitol, xylitol, erythritol, and a combination of two or three of said three polyols) is 10% (w / w) to 50% (w / w); in a preferred embodiment, the polyol is xylitol, wherein the amount of xylitol is 10% (w / w) to 50% (w / w); in another preferred embodiment, the polyol is erythritol, wherein the amount of erythritol is 10% (w / w) to 50% (w / w); (d) (b) and (c) plus alpha-bisabolol (6-methyl-2-(4-methylcyclohex-3-en-1-yl)hept-5-en-2-ol), chamazulene (7-ethyl-1,4-dimethylazulene), matrycine ([9-hydroxy-3,6,9-trimethyl-2-oxo-3,3a,4,5,9a,9b-hexahydroazuleno[4,5-b]furan-4-yl]acetate) ate), curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione), beta-caryophyllene (4,11,11-trimethyl-8-methylidenebicyclo[7.2.0]undec-4-ene), eugenol (2-methoxy-4-prop-2-enylphenol), camphor (1,7,7-trimethylbicyclo[2.2.1]heptane-2- at least one other anti-inflammatory component selected from the group consisting of 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane), cuminaldehyde (4-isopropylbenzaldehyde), thujone (4-methyl-1-propan-2-ylbicyclo[3.1.0]hexan-3-one), chlorhexidine (1,6-bis(4-chloro-phenylbiguanide)hexane), povidone iodine (1-ethenylpyrrolidin-2-one), cetylpyridinium chloride or cetylpyridinium bromide (1-hexadecylpyridinium chloride or 1-hexadecylpyridinium bromide), and ursolic acid, wherein the total amount of all other anti-inflammatory components (d) is 0.001% (w / w) to 2% (w / w). wherein the total of (a), (b), (c), and (d) must be 90% (w / w) to 100% (w / w).

[0056] In other words, the composition according to the present invention can contain up to 10% (w / w) of further components that may be added intentionally (e.g., to increase the flowability of the composition or to adjust the pH of the composition) or that are added together with any of components (a) to (d), such as adjuvants in carbomer products, or components in plant oils or plant extracts other than components (a), (b), (c) or (d).

[0057] In a preferred embodiment, the composition comprises a compound selected from groups (a), (b), (c), and (d) as defined in the first aspect and any of the embodiments disclosed herein, as well as L-ascorbic acid or a derivative thereof, dibutylhydroxytoluene, butylhydroxyanisole, superoxide dismutase, a carotenoid, astaxanthin, rutin or a derivative thereof, hesperidin, quercetin, catechin; gallic acid or a derivative thereof, allantoin (N-(2,5-dioxoimidazolidin-4-yl)urea) and a derivative thereof, glutathione or a derivative thereof, glutathione, β-carotene or a derivative thereof, ubiquinol, a polyphenol, hydrangea, turmeric, star anise, echinacea, Scutellaria root, Hypericum erectum, Chinese gall nut, Geranium herb thunbergii), rice, rice bran, comfrey, Japanese pepper (Xanthoxylum piperitum), labiatae (labiate), peony root, soybean, "natto" (soybean fermented with its own bacteria), tea leaf, clove, loquat, peony, horse chestnut, saxifrage, rooibos, rosemary, spirulina, chlorella, and dunaliella, bilirubin, cholesterol, tryptophan, histidine, thiotaurine, and hypotaurine, wherein the total amount of the one or more antioxidants is 0.001% (w / w) to 5% (w / w); and wherein the total amount of (a), (b), (c), (d) and the one or more antioxidants is 90.001% (w / w) to 100% (w / w).

[0058] Another preferred embodiment relates to a composition according to the first aspect consisting of groups (a), (b), (c) and (d) as defined in the first aspect and any of its embodiments, and one or more further components (e), wherein the total amount of all further components (e) is 10% (w / w) or less, preferably wherein the further components (e) are selected from the group consisting of (e1) extracts and oils, (e2) buffers, (e3) glycerides of methylparaben, (e4) glycerides of methylparaben, (e5) glycerides of methylparaben, (e6) glycerides of methylparaben, (e7) glycerides of methylparaben, (e8) glycerides of methylparaben, (e9) glycerides of methylparaben, (e10) glycerides of methylparaben, (e11) glycerides of methylparaben, (e12) glycerides of methylparaben, (e13) glycerides of methylparaben, (e14) glycerides of methylparaben, (e15) glycerides of methylparaben, (e16) glycerides of methylparaben, (e17) glycerides of methylparaben, (e18) glycerides of methylparaben, (e19) glycerides of methylparaben, (e19) glycerides of methylparaben, (e20) glycerides of methylparaben, (e21) glycerides of methylparaben, (e22) glycerides of methylparaben, (e23) glycerides of methylparaben, (e24) glycerides of methylparaben, (e25) glycerides of methylparaben, (e26) glycerides of methylparaben, (e27) glycerides of methylpara buffer, (e3) chelating agent, (e4) antioxidant, (e5) preservative, (e6) humectant, (e7) flavoring, (e8) vitamin, (e9) retinoid, (e11) amino acid, (e12) oral enhancing polyol, (e13) hydroxy acid, (e14) fluoride, (e15) sweetener, (e16) coloring, (e17) peptide, (e18) cooling agent, (e19) warming agent, (e20) tingling agent and (e21) emulsifiers, and (e22) further additives; and preferably, wherein the further component (e) comprises at least one component (e) selected from the group consisting of propolis (e1), lotus root extract (e1), and catechin (e4), wherein the amount of lotus root extract is 0.1% (w / w) to 5% (w / w), and the amount of catechin is 0.001% (w / w) to 5% (w / w), more preferably 0.2% (w / w) to 5% (w / w), and the amount of propolis is 0.01% (w / w) to 2% (w / w). ) (in addition to providing other important substances such as vitamins and antioxidants necessary for gum health, the presence of lotus root extract has the advantage that its cocoa-like taste increases the user's acceptance of the composition, thus improving its effectiveness as the user uses it more regularly; catechins are vasodilatory components that lead to improved blood circulation in the gums; propolis is produced in large quantities by honeybees, has antibiotic, antiviral and antifungal effects and is rich in essential oils, flavonoids, phenols and polysaccharides); Here, the totals of (a), (b), (c), (d), and (e) must always add up to 100%.

[0059] In a preferred embodiment, the present invention is directed to an oral care composition consisting of (a), (b), (c), (d) as defined in the first aspect and in the embodiments disclosed herein, and a further component (preferably component (e)); and wherein the further component (preferably component (e)) comprises at least one or more antioxidants (e4), preferably wherein the total amount of said one or more antioxidants is from 0.001% (w / w) to 5% (w / w); and optionally further components, preferably selected from the group (e1) to (e3) and (e5) to (e22); wherein the total of (a), (b), (c), and (d) is between 90% (w / w) and 99.999% (w / w), the total of (e4) is between 0.001% (w / w) and 5% (w / w), and the total of all further components (preferably component (e)) is between 0% (w / w) and 9.999% (w / w), and the total of (a), (b), (c), (d), and (e4) plus all further components, preferably selected from the group (e1) to (e3) and (e5) to (e22), must always add up to 100%.

[0060] In a preferred embodiment, the composition comprises one or more antioxidants selected from the group consisting of ascorbic acid, sodium ascorbyl phosphate, catechin, allantoin or its allantoinate form, and limonene, more preferably selected from the group consisting of sodium ascorbyl phosphate, C, EC, ECG, EGC, and EGCG, allantoin, allantoinate, and limonene, even more preferably selected from the group consisting of C, EC, ECG, EGC, and EGCG.

[0061] In another preferred embodiment, the oral care composition is essentially free of triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) (i.e., the amount of triclosan is 0.0001% (w / w) or less, more preferably 0.000001% (w / w) or less), and most preferably triclosan-free (i.e., triclosan is not present in the composition at analytically detectable levels, and the composition is triclosan-free).

[0062] Preferably, the oral care composition is in the form of a hydrogel. In a preferred embodiment, the viscosity of the composition is 10 Pas to 800 Pas at a shear rate of 1 1 / s and a temperature of 22°C (preferably measured using a rotational rheometer equipped with a 4° angle and a 40 mm diameter cone and plate with a standard smooth surface (stainless steel)). Unless otherwise specified, measurements were performed using a rotational rheometer equipped with a 4° angle and a 40 mm diameter cone and plate with a standard smooth surface at 22°C (±2°C). A viscosity of less than 10 Pas at a shear rate of 1 1 / s indicates that the composition between the splint and the user's gums / teeth is removed from the gum or tooth surface too quickly to have a long-lasting effect, as with mouthwash. A viscosity of more than 800 Pas at a shear rate of 1 1 / s no longer produces a consistent amount of composition from the dispenser, and it becomes difficult to distribute the composition evenly over the gums, teeth, or splint surface. The viscosity is particularly preferably in the range of 20 to 500 Pas at a shear rate of 1 1 / s, more preferably 20 to 200 Pas, and even more preferably 40 to 200 Pas, such as (60±20 Pas). It is also preferred if the yield point of the composition according to the present invention is 2 Pa or higher at a shear rate of 0 1 / s, more preferably in the range of 2 to 100 Pa, and even more preferably in the range of 10 to 40 Pa. It has been observed that the presence of 0.1% HA is insufficient to form a complete gel. While 0.3% HA already exhibits better gel behavior, compositions containing this concentration of HA without additional polymer still behave in part more like Newtonian fluids and do not exhibit the same good adhesive effect as formulations containing at least 0.4% (w / w) water-insoluble HA and, preferably, an additional water-insoluble polymer. Thus, the composition preferably comprises at least 0.4% (w / w) HA, more preferably at least 0.8% (w / w) water-insoluble polymer, wherein at least 0.4% (w / w) is HA. The range of viscosity profiles achieved through the use of HA and preferably a second water-insoluble polymer provides the user with a better sensory experience of application.If the product is too viscous, it will be difficult to spread evenly on the gum tissue.If the product has too low viscosity, the exposure time will be reduced, for example, by enhancing the saliva secretion reduction of the composition in the oral cavity.Hydrogels comprising water and at least one water-insoluble polymer can and may need to contain other substances, such as buffers (e.g., tris(hydroxymethyl)aminomethane (TRIS)), salts, complexing agents (e.g., EDTA disodium salt), and other solvents (e.g., propylene glycol).

[0063] In a preferred embodiment, the pH of the oral care composition is from pH 5.5 to pH 8, more preferably from pH 6 to pH 8, even more preferably from pH 6 to pH 7.2 or from pH 6.5 to pH 7.8, such as from pH 6.8 to pH 7.8, or even from pH 7.0 to pH 7.8.

[0064] The composition according to the present invention should not contain solid particles (abrasives), which scrub and thus irritate the gums, especially when the composition is used with a splint. Those skilled in the art understand that the abrasives used in oral care products (such as toothpaste) are either not soluble in the oral care composition or are present at a concentration higher than the solubilization concentration of the abrasive. For example, sodium bicarbonate (NaHCO3) is a well-known abrasive in toothpaste. The solubility (hereinafter referred to as SO2) of NaHCO3 in water at 20°C, 1013 mbar, and pH 7 is 93.4 g / L (93.4 g / 1000 g H2O = 9.34% (w / w)), that is, the composition according to the present invention may contain dissolved (solubilized) NaHCO3, but only at a concentration less than 9.34% (w / w). Tricalcium phosphate (Ca3(PO4)2) has a SO of 0.02 g / l (0.002% (w / w)), i.e., the composition according to the invention may contain dissolved (solubilized) (Ca3(PO4)2), but only at a concentration of less than 0.002% (w / w), while calcium hydroxyapatite (Ca 10(PO4)6(OH)2) is not soluble in water. As used herein, "not soluble (not SO)" means that the solution contains less than 0.0001% / w / w of the component. In a preferred embodiment, the composition does not contain solid particles and is calcium phosphate, e.g., calcium pyrophosphate (not Ca2O7P2 / SO), dicalcium phosphate (or calcium hydrogen phosphate) (CaHPO4 / SO: 0.1 g / l), tricalcium phosphate (or calcium phosphate or tricalcium orthophosphate) (Ca3(PO4)2 / SO: 0.02 g / l), calcium metaphosphate (cyclic condensation product orthophosphate (H3PO4), e.g., calcium trimetaphosphate has a six-membered ring system consisting of three oxygen atoms and three phosphorous atoms (SO: less than 0.02 g / l)), calcium polyphosphate (acyclic condensation product of ortho-phosphoric acid (SO: less than 0.02 g / l)), or calcium hydroxyapatite (Ca 10 (PO4)6(OH)2 / SO4; calcium or strontium carbonate (CaCO3 / SO4: 0.014 g / l; or SrCO3(SO4: 0.01 g / l)); sodium bicarbonate (also hydrogen carbonate - NaHCO3 / SO4: 93.4 g / l); silica, e.g., fused silica (SiO2 / SO4: 0.01 g / l), fumed silica (SO4: less than 0.12 g / l), precipitated silica (SO4: less than 0.12 g / l), hydrous silica (silicon dioxide with variable amounts of water in the formula, i.e., oxyacid H of silicium). 2n+2 Si n O 3n+1(where n is an integer equal to or greater than 1), for example, Si(OH)4 / (SO: less than 0.12 g / L) in which the Si atom is bridged by oxygen; diatomaceous earth (no SO); barium sulfate (SO: 0.022 g / L); wollastonite (Ca3[SiO9] / no SO); perlite (no SO), polymethyl methacrylate particles (PMMA / no SO), silicone beads (e.g., crosslinked siloxane particles such as Tospearl / SO: less than 0.012 g / L), and combinations of any of the foregoing. Commercially available abrasives include, for example, "Syloid" or Zeodent® -119, -118, -109, and -129.

[0065] In a preferred embodiment, the amount of each component selected from the group consisting of calcium pyrophosphate, calcium hydroxyapatite, diatomaceous earth, wollastonite, perlite, PMMA, silicon beads, if present, is 0.00001% (w / w) or less, and most preferably, these components are absent from the composition according to the invention.

[0066] In another preferred embodiment, if present, the amount of dicalcium phosphate in the composition is 0.008% (w / w) or less. In another preferred embodiment, if present, the amount of tricalcium phosphate in the composition is 0.0016% (w / w) or less. In another preferred embodiment, if present, the amount of calcium metaphosphate in the composition is 0.0016% (w / w) or less. In another preferred embodiment, if present, the amount of calcium polyphosphate in the composition is 0.0016% (w / w) or less. In another preferred embodiment, if present, the amount of calcium carbonate in the composition is 0.001% (w / w) or less. In another preferred embodiment, if present, the amount of strontium carbonate in the composition is 0.0008% (w / w) or less. In another preferred embodiment, if present, the amount of sodium bicarbonate is 7.4% (w / w) or less. In another preferred embodiment, if present, the amount of fused silica is 0.0008% (w / w) or less. In another preferred embodiment, the amount of fumed silica, if present, is 0.0009% (w / w) or less. In another preferred embodiment, the amount of precipitated silica, if present, is 0.0009% (w / w) or less. In another preferred embodiment, the amount of hydrous silica, if present, is 0.0009% (w / w) or less. In another preferred embodiment, the amount of barium sulfate, if present, is 0.0017% (w / w) or less. In another preferred embodiment, the amount of silicon beads, if present, is 0.0009% (w / w) or less.

[0067] In another preferred embodiment, the oral care composition is substantially free of calcium pyrophosphate, calcium hydroxyapatite, diatomaceous earth, wollastonite, perlite, PMMA, silicone beads, dicalcium phosphate, tricalcium phosphate, calcium metaphosphate, calcium polyphosphate, calcium carbonate, strontium carbonate, fused silica, fumed silica, precipitated silica, hydrous silica, silicone beads, and barium sulfate, i.e., the amount of any of these components in the composition is 0.001% (w / w) or less, regardless of the form (solubilized or solid) of any component.

[0068] In another preferred embodiment, the oral care composition is substantially free of calcium pyrophosphate, calcium hydroxyapatite, diatomaceous earth, wollastonite, perlite, PMMA, silicone beads, dicalcium phosphate, tricalcium phosphate, calcium metaphosphate, calcium polyphosphate, calcium carbonate, strontium carbonate, fused silica, fumed silica, precipitated silica, hydrous silica, silicone beads, and barium sulfate, i.e., the amount of any of these components in the composition is 0.001% (w / w) or less, regardless of the form (solubilized or solid) of any component.

[0069] More preferably, the composition contains: each component selected from the group consisting of calcium pyrophosphate, calcium hydroxyapatite, diatomaceous earth, wollastonite, perlite, PMMA, silicon beads in an amount of 0.00001% (w / w) or less, if present; dicalcium phosphate in an amount of 0.008% (w / w) or less, if present; each component selected from the group consisting of tricalcium phosphate, calcium metaphosphate, and calcium polyphosphate in an amount of 0.0016% (w / w) or less, and calcium carbonate in an amount of 0. The composition is preferably a composition in which the amount of strontium carbonate in the composition is 0.0008% (w / w) or less, the amount of fused silica is 0.0008% (w / w) or less, the amount of each component selected from the group consisting of fumed silica, precipitated silica, hydrous silica, and silicon beads is 0.0009% (w / w) or less, and the amount of barium sulfate is 0.0017% (w / w) or less, and even more preferably the composition is free of any of these components. In another preferred embodiment, the composition is a composition in which the amount of sodium bicarbonate is 7.4% (w / w) or less, preferably 1% (w / w) or less.

[0070] Protic Solvent (a) Protic solvents (a) in the context of the present invention are water, short-chain monohydric or polyhydric alcohols (e.g., methanol, ethanol, 1-propanol, 2-propanol, 1,2-propanediol (propylene glycol), (propane-1,2,3-triol) (glycerol), 1-butanol, etc.), short-chain primary and secondary amines, short-chain primary and secondary amides (e.g., formamide), and also pyridine 3-carboxamide, and polysorbates (e.g., TWEEN 20 (polyethylene glycol-sorbitan-monolaurate), TWEEN 40 polyoxyethylene-sorbitan-monopalmitate, and TWEEN 50 polyoxyethylene-sorbitan-monopalmitate). 80 (polyethylene glycol-sorbitan-monooleate). It is particularly preferably an orally acceptable protic solvent. Those skilled in the art will recognize that the total amount of all protic solvents in a composition cannot be less than the minimum possible amount or more than the maximum possible amount of all protic solvents in a composition according to the present invention (for example, the total amount of water and 1,2-propylene glycol (propane-1,2-diol), 1,3-butylene glycol (butane-1,3-diol), or 1,2-pentylene glycol (pentane-1,2-diol), when they are two solvents in a composition according to the present invention, cannot be less than 45% or more than 85% (w / w)).

[0071] In one preferred embodiment, (a) consists of water. In another preferred embodiment, (a) comprises water and one or more additional protic solvents. In another preferred embodiment, (a) consists of water and one or more protic solvents, which are preferably solvents that are in the liquid phase at standard ambient temperature and pressure (T=298.15 K and p=1013 hPa) and have a hydrogen atom bonded to oxygen, nitrogen, or fluoride, more preferably oxygen or nitrogen. In yet another preferred embodiment, (a) consists of water and at least one additional protic solvent, and the amount of water is at least 50% (w / w), more preferably 55% (w / w) to 85% (w / w), such as 55% (w / w) to 75% (w / w), more preferably 55% (w / w) to 70% (w / w), and even more preferably 55% (w / w) to 68% (w / w). In another preferred embodiment, (a) comprises water and propylene glycol. In yet another preferred embodiment, (a) consists of water and propylene glycol. In another preferred embodiment, (a) comprises water and pentane-1,2-diol. In yet another preferred embodiment, (a) consists of water and pentane-1,2-diol. In another preferred embodiment, (a) comprises water and ethanol. In another preferred embodiment, (a) consists of a mixture of water and ethanol. In another preferred embodiment, (a) comprises water and glycerol. In another preferred embodiment, (a) consists of water and glycerol. In another preferred embodiment, (a) comprises water, 1,2-propylene glycol, and ethanol (more preferably consists of these three components), and the amount of water is 50% (w / w) to 76% (w / w), the amount of 1,2-propylene glycol is 2% (w / w) to 6% (w / w), and the amount of ethanol is 0.5% (w / w) to 3% (w / w), and the total of all protic solvents (a) in the composition is at most 85% (w / w).In another preferred embodiment, (a) comprises, or more preferably consists of, water and one or more C1-C5 alcohols (e.g., ethanol, 1-propanol or 2-propanol, 1,2-propylene glycol, 1,2-pentylene glycol, and glycerol), more preferably a C1-C4 alcohol (e.g., a mono- or diol such as ethanol, 1-propanol or 2-propanol, 1,2-propanediol, 1-butanol or 2-butanol, or glycerol), even more preferably a C1-C3 alcohol (e.g., ethanol, 1-propanol or 2-propanol, 1,2-propanediol, or glycerol). In a further preferred embodiment, (a) comprises water and a further protic solvent, preferably propylene glycol. The amount of the further protic solvent, preferably 1,2-propylene glycol, is preferably 1.5% (w / w) to 20% (w / w), more preferably 3% (w / w) to 20% (w / w), and even more preferably 3% (w / w) to 10% (w / w). In another preferred embodiment, (a) comprises water and another protic solvent, preferably propylene glycol, and the amount of water is 50% (w / w) to 70% (w / w) (e.g., 57% (w / w) to 67% (w / w)), and the amount of the further protic solvent, preferably 1,2-propylene glycol, and the further protic solvent, preferably 1,2-propylene glycol, is 3% (w / w) to 8% (w / w) (e.g., around 5.9% (w / w), such as 5.3% (w / w) to 6.4% (w / w)). In a particularly preferred embodiment, (a) consists of water and 1,2-propylene glycol. In another preferred embodiment, (a) comprises water, 1,2-pentylene glycol, and ethanol (more preferably consists of these three components), and the amount of water is 50% (w / w) to 76% (w / w), the amount of 1,2-pentylene glycol is 2% (w / w) to 6% (w / w), and the amount of ethanol is 0.5% (w / w) to 3% (w / w), and the total of all protic solvents in the composition is at most 85% (w / w).In yet another preferred embodiment, (a) comprises, more preferably consists of, water and at least one further protic solvent selected from the group consisting of 1,2-propylene glycol, 1,3-butylene glycol, 1,2-pentanediol, glycerol, and ethanol, and the amount of water is 50% (w / w) to 66% (w / w), the amount of 1,2-propylene glycol is 1% (w / w) to 5% (w / w), and 1, The amount of 3-butylene glycol is from 1% (w / w) to 5% (w / w), the amount of 1,2-pentylene glycol is from 1% (w / w) to 6% (w / w), the amount of glycerol is from 1.5% (w / w) to 15% (w / w), and the amount of ethanol is from 0.5% (w / w) to 5% (w / w), more preferably from 0.5% (w / w) to 3% (w / w), wherein the sum of all protic solvents in the composition is at most 85% (w / w).

[0072] In another preferred embodiment, (a) consists of a mixture of water and two or three other protic solvents, preferably selected from the group consisting of ethanol, 1,2-propylene glycol, 1,2-pentanediol, and glycerol, such as ethanol and 1,2-propylene glycol, and / or 1,2-pentanediol. In another preferred embodiment, (a) consists of a mixture of water and three other protic solvents, preferably selected from the group consisting of glycerol, ethanol, 1,2-pentylene glycol, and 1,2-propylene glycol. This can be achieved, for example, by using carbomer gel, which often contains 1,2-propylene glycol in addition to water, and by using ethanolic plant extracts (e.g., chamomile) or ethanolic propolis products in the production of compositions according to the invention. Glycerol and 1,2-pentanediol can be added to improve the sensory properties and stability of the composition. Additionally, alcohols such as ethanol aid in the formation of a gel when combined with water and hyaluronic acid, such as the Na salt of hyaluronic acid.

[0073] In another preferred embodiment, (a) is a mixture of water and a monohydric or polyhydric C1, C2, C3, C4, C5, or C6 alcohol (preferably methanol, ethanol, 1-propanol, 2-propanol, 1,2-ethylene glycol, 1,2-propylene glycol, 1,3-butylene glycol, 1,2-pentylene glycol, 1,2-hexylene glycol, 1,2,3-propanetriol (glycerol), 1-butanol, 2-butanol, 2-methyl-1-propanol, 2-methyl-2-propanol), C1, C2, or C3 alcohol. The protic solvent (a) comprises, and more preferably consists of, a carboxylic acid (formic acid, acetic acid, propionic acid, preferably formic acid or acetic acid, more preferably acetic acid) and at least one solvent selected from the group consisting of any combination of the foregoing; more preferably, the protic solvent in addition to water is at least one solvent selected from the group consisting of ethanol, 1-propanol, 2-propanol, 1,2-propylene glycol, 1,3-butylene glycol, glycerol, 1,2-pentylene glycol, acetic acid, or any combination of the foregoing. In yet another embodiment, the protic solvent (a) consists of water. In another preferred embodiment, the protic solvent (a) consists of a combination of water and one or more solvents selected from the group consisting of ethanol, 1-propanol, 2-propanol, 1,2-propylene glycol, glycerol, 1,3-butylene glycol, and 1,2-pentylene glycol.

[0074] In a more preferred embodiment, (a) is at least 60%, more preferably at least 98%, even more preferably at least 99%, such as at least 99.9%, by weight of all protic solvents in the composition, or water and a solvent selected from the group consisting of C2 and C3 chain monoalcohols (e.g., ethanol, 1-propanol, 2-propanol), short chain polyhydric alcohols (e.g., 1,2-propylene glycol, 1,3-butylene glycol, 1,2-pentylene glycol, and glycerol), polysorbates (e.g., TWEEN 20, TWEEN 40, and TWEEN 80), formic acid, acetic acid, and primary amides (e.g., pyridine-3-carboxamide), and even more preferably ethanol, 1-propanol, 2-propanol, 1,2-propylene glycol, 1,3-butylene glycol, 1,2-pentylene glycol, glycerol, TWEEN 20, TWEEN 40, TWEEN 80, acetic acid, and pyridine-3-carboxamide; or any of the other preferred protic solvent combinations disclosed herein (those skilled in the art will understand that trace amounts of other protic solvents may be present in compositions according to the present invention, for example, due to being auxiliary or residual extractants of the extraction product (see, e.g., turmeric extraction medium below) or the water-insoluble polymer product). In another preferred embodiment, the amount of water is at least 70% (based on the total weight of all protic solvents in the composition).In a further preferred embodiment, the amount of water is at least 80% (based on the total weight of all protic solvents in the composition), and the amount of any one of the additional protic solvents ethanol, 1-propanol, 2-propanol, 1,3-butylene glycol, 1,2-propylene glycol, 1,2-pentylene glycol, acetic acid, and pyridine-3-carboxamide (if present) is each independently of the other 5% or less (based on the total weight of all protic solvents in the composition), the amount of glycerol (if present) is 15% or less (based on the total weight of all protic solvents in the composition), and the amount of TWEEN 20, TWEEN 40, and TWEEN 80 (if present) is each independently of the other 0.01% or less (based on the total weight of all protic solvents in the composition).

[0075] More preferably, the amounts of 1-propanol, 2-propanol, acetic acid, and pyridine-3-carboxamide are each independently 1% or less, based on the total weight of all protic solvents in the composition. Those skilled in the art will understand that the total weight of all protic solvents (a) in a composition must always total 100% when based on the total weight of all protic solvents in the composition, while the total amount of (a) is always in the range of 45% (w / w) to 85% (w / w), based on the total weight of all components (a), (b), (c), (d), and (optionally) (e) of the composition according to the present invention.

[0076] Water-insoluble polymer (b) At least one water-insoluble polymer (b) is included in the oral care composition. Group (b) includes at least hyaluronic acid (HA) (including any one of its sodium (Na) salt, lithium (Li) salt, potassium (K) salt, magnesium (Mg) salt, and calcium (Ca) salt, any of the aforementioned thiolated forms (e.g., HA-cysteine ​​ethyl ester), or crosslinked forms (e.g., urea-crosslinked HA, or any of the crosslinked HA resulting from the reaction mentioned under the definition. Crosslinked HA or its salts are commercially available).

[0077] In addition to its ability to bind large amounts of water (up to 6 liters per gram of HA), HA also has mucoadhesive properties. Water-insoluble mucoadhesive polymers, especially in the form of hydrogels, can be used to maintain the further components of the oral care composition according to the invention on oral surfaces, such as the gums, for a prolonged period of time. HA is known to be an essential component of intact, healthy gums and oral mucosal tissues, and it induces early formation of granulation tissue, inhibits inflammation, promotes epithelial turnover, and also promotes vascularization of connective tissue.

[0078] In a preferred embodiment, the HA, such as HA or its Na or alkaline earth salt (preferably selected from Mg or Ca salts, more preferably Mg salt), has a molar mass of 5 kDa to 2000 kDa, preferably 5 kDa to 200 kDa, for example 8 kDa to 12 kDa, 10 kDa to 50 kDa; or 201 kDa to 2000 kDa, for example 1200 kDa to 1800 kDa); or a combination of HA polymers with a molar mass of 5 kDa to 2000 kDa, such as a combination of at least two HA polymers selected from the group consisting of polymers with a molar mass between 5 kDa and 200 kDa and 160 kDa to 2000 kDa.

[0079] Preferably, the HA (e.g., a salt thereof, preferably a sodium salt or magnesium salt thereof) used in the present invention has a molecular weight (MW) of 1 kDa to 5,000 kDa, preferably 5 kDa to 2,000 kDa, e.g., 2 kDa to 500 kDa, and more preferably a low-molecular-weight HA (or a salt thereof, such as a sodium salt) of 5 kDa to 200 kDa, e.g., 5 kDa to 150 kDa, or 5 kDa to 60 kDa, or 7 kDa to 55 kDa. The HA can be a linear polymer, a crosslinked polymer, or a mixture of a linear polymer and a crosslinked polymer, HA, or a salt of HA, preferably a sodium salt of HA, e.g., Hyamax (sodium hyaluronate with a molar mass of 8 kDa to 12 kDa). Low-molecular-weight HA (e.g., a salt thereof) has the advantage of easily penetrating (mucosal) membranes. This is particularly true for HA having a molecular weight below 200 kDa, e.g., a molecular weight below 150 kDa. In a preferred embodiment, the HA is present as a salt, preferably its Na salt. In another embodiment, the HA is thiolated HA or a salt thereof, preferably the Na salt, such as an HA-cysteine ​​ethyl ester conjugate (or a salt thereof). In a further preferred embodiment, the HA is an HA-cysteine ​​ethyl ester conjugate or a salt thereof, preferably the Na salt. In a further preferred embodiment, at least one HA in the composition according to the invention is an alkali salt (preferably the Na, Li, or K salt, more preferably the Na salt; or the Mg salt) of HA (preferably 5 kDa to 2000 kDa, more preferably 5 kDa to 200 kDa, e.g., 8 kDa to 12 kDa, 10 kDa to 50 kDa; or 201 kDa to 2000 kDa, preferably 1200 kDa to 1800 kDa).

[0080] In another preferred embodiment, at least one HA in the composition according to the present invention is cross-linked HA. In yet another preferred embodiment, the HA is cross-linked at the hydroxyl group, NHCOCH3 group, or carboxyl group. Those skilled in the art will recognize cross-linking agents for carboxyl groups. Preferred examples of modifications to HA molecules are dicyclohexylcarbodiimide, N-hydroxysuccinimide (NHS), benzotriazol-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate, 1-hydroxy-7-azobenzotriazole (HOAt), carbonyldiimidazole, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC). Preferred examples for modifying hydroxyl groups (-OH) in HA molecules are 1,4-butanediol diglycidyl ether (BDDE), divinyl sulfone (DVS), glutaraldehyde, cyanogen bromide, octylsuccinic anhydride, acid chlorides, methacrylic anhydride, and sodium periodate. Further cross-linking of HA can be achieved, for example, by using aldehyde-functionalized HA (based on the introduction of a double bond into the glucuronic acid of hyaluronic acid (HA) by biodegradation of HA using hyaluronic acid lyase, followed by the generation of a free aldehyde group at the non-reducing end of hyaluronic acid via ozonolysis and subsequent reduction of the generated ozonide; see, for example, Ruhela et al. in Bioconjugate Chem. 2006, 17, 5, 1360-1363).The resulting aldehyde-functionalized HA was then synthesized into methacrylate chitosan, cystamine dihydrochloride, carboxyethyl-modified chitosan, hydrazide-functionalized poly(γ-glutamic acid), collagen, N-succinyl-chitosan, carbohydrazide-modified gelatin, amino-modified HA (each time, DCC based on Schiff base), hydrazine-modified elastin-like protein, hydrazide-modified HA (each time, DCC based on hydrazone), adipic acid dihydrazide-modified HA and dialdehyde-modified pectin, hydrazide-modified HA and betaine. Aldehyde-terminated F127 triblock polymer, hydrazine-modified HA and aldehyde-modified HA and catalyst, carbohydrazide-modified carboxymethylcellulose and aldehyde-modified HA, gallol and hydrazide-modified HA, and aldehyde-modified HA, norbornene-modified HA and aldehyde- or hydrazide-modified HA (hydrazone-based DCC in each case), S-protected thiolated HA, thiolated HA and PEGDA (polyethylene glycol diacrylate), thiolated HA and gold nanoparticles, thiolated hydroxylated HA, thiolated HA and acrylated HA, thiol- and hydrazide-modified HA and oxidized alginate, thiolated HA and thiolated carboxymethylcellulose, pyridyl disulfide-modified HA and macrocrosslinker PEG-dithiol, aldehyde-modified HA and 3,3'-dithiobis(propionic acid hydrazide) (each time a disulfide-based DCC), furan- and tyramine-modified HA and maleimide-modified PEG, HA-furan-adipic dihydrazide (adipic dihydrazide) drazide) and HA-furan-aldehyde, furan-modified HA and maleimide-PEG (each a Diels-Alder-based DCC), benzoxaborole-modified HA, phenylboronic acid-modified HA and poly(vinyl alcohol), 3-aminophenylboronic acid-modified HA and saccharide, boronic acid-modified HA and fructose-modified HA, and boronic acid-modified HA and maltose-modified HA (each a boronate ester-based SCC).

[0081] One preferred example is a BDDE-crosslinked HA molecule. Preferred examples of modification reactions of the -NHCOCH3 group of the HA molecule include deacetylation, amidation, hemiacetylation, and hemiacetal formation, among others. The amidation method is used to deacetylate the N-acetyl groups of HA, which can then react with acid, and is usually performed using hydrazine sulfate. (See, e.g., J. Tissue Eng, 2017, Jan-Dec; 8: 2041731417726464.) In a preferred embodiment, the amount of HA is 0.4% to 5%, such as 0.4% to 2.5%, more preferably 0.8% to 5%, such as 0.8% to 2.5%, (w / w).

[0082] The presence of HA can induce early formation of granulation tissue, inhibit inflammation, and promote epithelial turnover and connective tissue vascularization. The presence of another water-insoluble polymer, for example in the form of carbomer or mannan, allows for more precise adjustment of the viscosity of the composition than with hyaluronic acid alone and enhances hydrogel formation. Viscosity, among other things, determines the retention time of the gel between the aligner splint and the gums / teeth when the aligner splint is worn. Higher viscosity increases retention time, while too high a viscosity impairs the distribution of the gel between the aligner splint and the gums / teeth when the aligner splint is worn. Additionally, the mucoadhesive effect of HA aids in the retention time of the active ingredient on the gum surface.

[0083] It has been observed that the hydrogel formulation increases with the use of at least one additional water-insoluble polymer in addition to HA, preferably the amount of HA is between 0.8% (w / w) and 2.5% (w / w).

[0084] Thus, in another preferred embodiment, (b) comprises HA and at least one additional water-insoluble polymer, preferably selected from the group consisting of gelatin, (cross-linked) poly(meth)acrylates such as (cross-linked) polyacrylic acid (e.g., carbomer), (cross-linked) polyurethane polymers, (trimethylated) chitosan, alginate, pectin, povidone-iodine, mannans, preferably water-insoluble polysaccharides such as D-galacto-D-mannan, carboxymethylcellulose, hydroxyethylcellulose, ethylcellulose, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and the Na, K, or Li salts of any of the foregoing. In addition to its ability as a water-insoluble polymer, D-galacto-D-mannan is an antioxidant that can protect cell walls, and is therefore preferred. All of these additional water-insoluble polymers are commercially available.

[0085] In a further preferred embodiment, (b) comprises, or more preferably consists of, HA and at least one other water-insoluble, preferably mucoadhesive polymer selected from the group consisting of polysaccharides (preferably mannan), carboxymethylcellulose, hydroxyethylcellulose, ethylcellulose, methylcellulose, hydroxypropylcellulose (e.g., low-substituted hydroxypropylcellulose CAS 9004-64-2), hydroxypropylmethylcellulose, (crosslinked) polyacrylic acid, preferably carbomer, and the Na, K, or Li salts of any of the foregoing (e.g., Na carboxymethylcellulose).

[0086] In a preferred embodiment, (b) comprises, more preferably consists of, AH and at least one additional water-insoluble polymer selected from the group consisting of carbomer, mannan (preferably D-galacto-D-mannan), and cellulose (preferably hydroxypropyl cellulose, carboxymethyl cellulose, or a Na salt or K salt of carboxymethyl cellulose), and even more preferably consists of AH and at least one additional water-insoluble polymer selected from the group consisting of D-galacto-D-mannan and carbomer.

[0087] In a further preferred embodiment, (b) comprises, more preferably consists of, HA and one additional water-insoluble polymer selected from the group consisting of D-galacto-D-mannan and carbomer, and even more preferably consists of D-galacto-D-mannan, wherein the total amount of all water-insoluble polymers is 0.9% (w / w) to 5% (w / w), and wherein the amount of hyaluronic acid is at least 0.8% (w / w).

[0088] In a preferred embodiment, the total amount of (b) is 0.8% (w / w) to 5% (w / w), and the amount of HA is 0.4% (w / w) to 3% (w / w), more preferably 0.8% (w / w) to 2.5% (w / w), such as 0.8% (w / w) to 2% (w / w), and the amount of at least one further water-insoluble polymer is 0.4% (w / w) to 2% (w / w). In a more preferred embodiment, the total amount of (b) is 0.8% (w / w) to 5% (w / w), and the amount of HA is 0.4% (w / w) to 3% (w / w), and the amount of at least one further water-insoluble polymer, preferably carbomer, cellulose, or mannan, is 0.03% (w / w) to 2% (w / w).

[0089] In a further preferred embodiment, (b) comprises, more preferably consists of, AH and carbomer, wherein the amount of carbomer is 0.03% (w / w) to 2% (w / w), more preferably 0.3% (w / w) to 1.6% (w / w), or 0.03% (w / w) to 0.9% (w / w). In a further preferred embodiment, (b) comprises, more preferably consists of, AH and at least one carbomer selected from the group consisting of carbomers having a viscosity (at 25°C, 1.013 bar, 0.5%, pH 7.3-7.8) of 4000 mPa*s to 45000 mPa*s, such as 1000 mPa*s to 45000 mPa*s, more preferably 25000 mPa*s to 45000 mPa*s, such as Carbomer 30,500 to 39,400 (e.g. Carbopol 5984) or Carbomer 35000 (e.g. Carbopol 974P). In a further preferred embodiment, (b) comprises, more preferably consists of, AH and at least one carbomer selected from the group consisting of carbomers having a viscosity of 1000 mPa*s to 45000 mPa*s, such as 25000 mPa*s to 45000 mPa*s, for example Carbomer 30,500 to 39,400 (e.g., in Carbopol 5984) or Carbomer 35000 (e.g., Carbopol 974P), wherein the viscosity was determined under specified conditions (0.5% concentration at 25°C and 1.013 bar, pH 7.3 to 7.8) using an SI Analytics™ Ubbelohde viscometer with ring markings for verification by manual measurement by Fisherscientific, Schwerte, Germany. In a further preferred embodiment, (b) comprises AH and a carbomer, preferably a carbomer having a viscosity of 4000 mPa*s to 45000 mPa*s, such as 25000 mPa*s to 45000 mPa*s (at 25°C and 1.013 bar, 0.5%, pH 7.3 to 7.8), and the amount of carbomer is 0.03% (w / w) to 2% (w / w), such as 0.3% (w / w) to 0.9% (w / w).Preferably, the carbomer has a viscosity of 25,000 mPa*s to 45,000 mPa*s (determined using an Ubbelohde viscometer at 25°C and 1.013 bar in a 0.5% aqueous solution, pH 7.3 to 7.8), e.g., Carbomer Gel pH 6.5 NRF S43. In a further preferred embodiment, (b) comprises, more preferably consists of, HA (preferably the amount of HA is 0.8% (w / w) to 2.5% (w / w)) and carbomer, preferably a carbomer having a viscosity of 4,000 mPa*s to 45,000 mPa*s, more preferably 25,000 mPa*s to 45,000 mPa*s, and the amount of carbomer is 0.03% (w / w) to 2% (w / w), preferably 0.3% (w / w) to 0.9% (w / w).

[0090] In another preferred embodiment, (b) comprises, more preferably consists of, HA (preferably, the amount of HA is 0.8% (w / w) to 2.5% (w / w)) and mannan. Preferably, the mannan is D-galacto-D-mannan, more preferably selected from the group consisting of D-galacto-D-mannan derived from Caesalpinia spinosa gum (CAS 39300-88-4), D-galacto-D-mannan derived from carob (CAS 11078-30-1), and D-galacto-D-mannan polysaccharide (CAS 9000-40-2). However, D-galacto-D-mannan derived from other sources, such as Adenanthera pavonina, Cyamopsis tetragonolobus, Caesalpinia pulcherrima, carob, and Sophora japonica, or bacteria, can also be used. In a further preferred embodiment, b) comprises, and more preferably consists of, AH (preferably, the amount of HA is 0.8% (w / w) to 2.5% (w / w)) and mannan, preferably D-galacto-D-mannan, wherein the amount of mannan is 0.5% (w / w) to 2.5% (w / w), more preferably 0.7% (w / w) to 1.5% (w / w), or 0.8% (w / w) to 1.3% (w / w).

[0091] In a further preferred embodiment, (b) comprises, more preferably consists of, AH (preferably the amount of HA is 0.8% (w / w) to 2.5% (w / w)) and a cellulose preferably selected from the group consisting of carboxymethylcellulose, carboxymethylcellulose, hydroxyethylcellulose, ethylcellulose, methylcellulose, hydroxypropylcellulose, and a Na salt or K salt of any of the foregoing, more preferably a Na salt, more preferably selected from hydroxypropylcellulose and Na carboxymethylcellulose. In a further preferred embodiment, (b) comprises, more preferably consists of AH (preferably the amount of HA is 0.8% (w / w) to 2.5% (w / w)) and a cellulose, preferably hydroxypropylcellulose, carboxymethylcellulose, or a Na salt of any of the foregoing, wherein the amount of cellulose is 0.5% (w / w) to 2.5% (w / w), more preferably 0.7% (w / w) to 1.5% (w / w) or 0.7% (w / w) to 1.3% (w / w).

[0092] Polyol (c) The composition according to the invention comprises at least one polyol (d) selected from the group consisting of xylitol, erythritol, and sorbitol.

[0093] The benefits of the three sugar alcohols are their anti-cariogenic properties as well as their function as humectants and sweeteners, i.e., the polyols are beneficial to gum health, tooth health, overall mouth feel, and user acceptance of the composition. Without being bound by explanation, it can be assumed that the three polyols cannot be metabolized by cariogenic bacteria, such as Streptococcus mutans, resulting in the death of the bacteria. This also prevents them from adhering to the tooth surface as plaque bacteria. By preventing plaque, the colonization of other types of bacteria is also prevented. In a preferred embodiment, (c) comprises, more preferably consists of, at least one polyol selected from the group consisting of xylitol and erythritol, and more preferably wherein the amount of xylitol or erythritol is 10% (w / w) to 45% (w / w), such as in the range of 10% (w / w) to 50% (w / w), more preferably 25% (w / w) to 40% (w / w), even more preferably 15% (w / w) to 35% (w / w), such as in the range of 25% (w / w) to 35%, (w / w), for example 30%±2% (w / w).

[0094] In a preferred embodiment, (d) consists of xylitol, preferably the amount of xylitol is from 10% (w / w) to 50% (w / w), more preferably from 10% (w / w) to 45% (w / w), such as in the range of 25% (w / w) to 40% (w / w), even more preferably from 15% (w / w) to 35% (w / w), such as in the range of 25% (w / w) to 35%, (w / w), for example 30%±2% (w / w).

[0095] In another preferred embodiment, (d) consists of sorbitol, preferably the amount of sorbitol is 10% (w / w) to 50% (w / w), more preferably 15% (w / w) to 50% (w / w), even more preferably 15% (w / w) to 45% (w / w), such as in the range of 25% (w / w) to 40% (w / w) or in the range of 25% (w / w) to 35% (w / w), for example 30%±2% (w / w).

[0096] In another preferred embodiment, (d) consists of erythritol, preferably the amount of erythritol is 10% (w / w) to 50% (w / w), more preferably 15% to 50% (w / w), even more preferably 15% to 45% (w / w), such as in the range of 25% to 40% or in the range of 25% (w / w) to 35% (w / w), for example 30%±2% (w / w).

[0097] In another preferred embodiment, a combination of two or three of the three polyols can be present, as long as the total of the combination is at least 10% (w / w) and at most 50% (w / w).

[0098] Anti-inflammatory component (d) In addition to (b) and (c), the composition according to the present invention further comprises at least one other anti-inflammatory component (d) selected from the group consisting of alpha-bisabolol, chamazulene, matricin, eugenol, curcumin, camphor, cineole, thujone, ursolic acid, beta-caryophyllene, chlorhexidine, povidone iodine, cetylpyridinium chloride, and cetylpyridinium bromide, more preferably selected from the group consisting of alpha-bisabolol, chamazulene, matricin, eugenol, curcumin, beta-caryophyllene, chlorhexidine, povidone iodine, and cetylpyridinium chloride or cetylpyridinium bromide, even more preferably selected from the group consisting of alpha-bisabolol, chamazulene, matricin, curcumin, beta-caryophyllene, chlorhexidine, and cetylpyridinium chloride. Preferably, the total amount of all other anti-inflammatory components (d) is 0.001% (w / w) to 2% (w / w), preferably 0.001% (w / w) to 1.5% (w / w), 0.001% (w / w) to 0.5% (w / w). The anti-inflammatory component (d) can be added to the composition in isolated form (e.g., purchased from Merck), or in some cases, in the form of, for example, a plant oil or plant extract. In the latter case, information regarding the content of the anti-inflammatory component (d) in the oil or extract can be received from the manufacturer, or a person skilled in the art can determine the amount using methods known in the art, for example, using GC / FID and commercially available standards for each component as an internal reference.

[0099] Preferably, (d) consists of one or more compounds selected from the group consisting of alpha-bisabolol, chamazulene, matricin (in each case from a natural source, e.g., chamomile), eugenol (from a natural source, e.g., cloves), curcumin (from a natural source, e.g., turmeric), beta-caryophyllene (from a natural source, e.g., sage or Eucalyptus globulus), camphor, cineole and thujone (from a natural source, e.g., sage), and ursolic acid (from a natural source, e.g., sage); more preferably, one or more compounds selected from the group consisting of alpha-bisabolol, chamazulene, matricin, eugenol, beta-caryophyllene, curcumin; even more preferably, one or more compounds selected from the group consisting of alpha-bisabolol, chamazulene, matricin, curcumin, beta-caryophyllene. In another preferred embodiment, (d) consists of one component selected from the group consisting of chlorhexidine and cetylpyridinium chloride or cetylpyridinium bromide, more preferably chlorhexidine and cetylpyridinium chloride.

[0100] In one preferred embodiment, (d) comprises eugenol, more preferably consists of eugenol. In another more preferred embodiment, (d) comprises alpha-bisabolol. In yet another more preferred embodiment, (d) comprises chamazulene. In yet another more preferred embodiment, (d) comprises matricin. In yet another more preferred embodiment, (d) consists of alpha-bisabolol, chamazulene, matricin, or a combination of two or three of the foregoing. In yet another more preferred embodiment, (d) comprises curcumin, more preferably consists of curcumin. In yet another more preferred embodiment, (d) comprises beta-caryophyllene, more preferably consists of beta-caryophyllene. In yet another more preferred embodiment, (d) comprises chlorhexidine, more preferably consists of chlorhexidine. In yet another more preferred embodiment, (d) comprises cetylpyridinium chloride, more preferably consists of cetylpyridinium chloride. In yet another more preferred embodiment, (d) comprises, and more preferably consists of, cetylpyridinium bromide.

[0101] In yet another more preferred embodiment, (d) consists of one or more components selected from the group consisting of alpha-bisabolol, chamazulene, matricin, a combination of two or three of the foregoing, curcumin, and beta-caryophyllene, preferably wherein the amount of (d) is 0.001% (w / w) to 0.06% (w / w), more preferably 0.005% (w / w) to 0.04% (w / w), and even more preferably 0.005% (w / w) to 0.02% (w / w). In yet another preferred embodiment, (d) consists of chlorhexidine, preferably wherein the amount of (d) is 0.001% (w / w) to 0.1% (w / w), more preferably 0.001% (w / w) to 0.06% (w / w), even more preferably 0.005% (w / w) to 0.04% (w / w), or even more preferably 0.005% (w / w) to 0.02% (w / w). In yet another preferred embodiment, (d) consists of cetylpyridinium chloride, preferably wherein the amount of (d) is 0.001% (w / w) to 0.1% (w / w), more preferably 0.001% (w / w) to 0.06% (w / w), even more preferably 0.005% (w / w) to 0.04% (w / w), or even more preferably 0.005% (w / w) to 0.02% (w / w). In yet another preferred embodiment, (d) consists of cetylpyridinium bromide, preferably wherein the amount of (d) is 0.001% (w / w) to 0.1% (w / w), more preferably 0.001% (w / w) to 0.06% (w / w), even more preferably 0.005% (w / w) to 0.04% (w / w), or even more preferably 0.005% (w / w) to 0.02% (w / w).

[0102] In another preferred embodiment, for example, when the composition is provided for a longer period of time or when the user does not have severe irritation, the composition does not contain (i.e., does not include) a component selected from the group consisting of chlorhexidine, cetylpyridinium chloride, cetylpyridinium bromide, and povidone iodine.

[0103] In a further preferred embodiment, component (d) is provided in the form of a vegetable oil or vegetable extract added to the composition according to the invention. The plant-derived oil and plant-derived extract are preferably selected from the group consisting of chamomile (Matricaria chamomilla), clove (Syzygium aromaticum), rosemary (Salvia rosmarinus), turmeric (Curcuma longa), and sage (Salvia officinalis), more preferably from the group consisting of chamomile (Matricaria recutita), clove (Syzygium aromaticum), rosemary (Salvia rosmarinus), turmeric (Curcuma longa), and sage (Salvia officinalis), and even more preferably from the group consisting of chamomile (Matricaria recutita), clove (Syzygium aromaticum), rosemary (Salvia rosmarinus), turmeric (Curcuma longa), and sage (Salvia officinalis), and even more preferably from the group consisting of chamomile (Matricaria recutita) and turmeric (Curcuma longa).

[0104] Important constituents in chamomile (preferably the flowers) are, inter alia, matricin (procamazulene, (-)-(3S,3aR,4S,9R,9aS,9bS)-9-hydroxy-3,6,9-trimethyl-2-oxo-3,3a,4,5,9a,9b-hexahydroazuleno-[4,5-b]furan-4-yl acetate), chamazulene (7-ethyl-1,4-dimethylazulene), and alpha-bisabolol ((2S)-6-methyl-2-[(1S)-4-methylcyclohex-3-en-1-yl]hept-5-en-2-ol) (anti-inflammatory, (mucosal) skin soothing). Chamazulene, a secondary product of matriline (produced by the separation of acetic acid and water; both substances have anti-inflammatory properties), is readily soluble in nonpolar solvents and lower alcohols such as ethanol or 1,2-propanediol; alpha-bisabolol, which is readily soluble in ethanol and insoluble in water, accounts for up to 45% of chamomile essential oil. Under certain extraction conditions, matriline is converted to chamazulene.

[0105] Thus, in a preferred embodiment, component (d) is provided in the form of an extract, preferably an alcoholic extract of chamomile, preferably an alcoholic extract of chamomile flowers, in which the extraction medium comprises an (aqueous) alkanol having 1 to 4 carbon atoms, preferably ethanol or 1,2-propanediol, and the amount of alkanol in the extraction medium is 40% (w / w) to 100% (w / w) based on the weight of the extraction medium. Extraction of chamomile flowers is typically carried out at a temperature ranging from 5°C to 60°C. The extract typically contains at least 4 parts by weight of extract, preferably 4 to 8 parts by weight, and in particular 5 to 6 parts by weight, of the dry weight of fresh chamomile (determined by drying a sample in a drying cabinet at 105°C for 3 hours). Chamomile extracts, particularly those approved for cosmetic and medical applications, are commercially available, e.g., Kamillosan (PZN: 00565073). The provider can provide information regarding the content of alpha-bisabolol, matricin, and / or chamazulene in the extract. In a further preferred embodiment, component (d) is provided in the form of a CO2 extract from chamomile, preferably from chamomile flowers. Such a method is well known in the art, for example, from EP 0058365. Equipment for such extraction (e.g., manufactured by Separeco) and CO2 extraction (e.g., manufactured by Flavex, DE-Oko-013 product number 019.002) are commercially available. The provider can provide information regarding the content of alpha-bisabolol, matricin, and / or chamazulene in the extract.

[0106] In a further preferred embodiment, the composition according to the invention comprises alpha-bisabolol as component (d), preferably in an amount of at least 0.001% (w / w), such as at least 0.003% (w / w), for example 0.003% (w / w) to 1.5% (w / w), for example 0.005% (w / w) to 1.2% (w / w) or 0.005% (w / w) to 1.5% (w / w), for example 0.007% (w / w) to 1.1% (w / w) or 0.007% (w / w) to 1.5% (w / w), or for example 0.003% (w / w) to 0.008% (w / w) or 0.003% (w / w) to 1.5% (w / w). Those skilled in the art will know how to determine the amount of alpha-bisabolol in a composition using methods known in the art, for example, via GC / MS and GC / FID using a GC instrument (GC-FID) (Shimadzu, Model 17A) equipped with a fused silica capillary column ((SBP5-Supelco, 30 m x 0.25 mm ID, 0.25 μm film thickness) connected to a flame ionization detector. The dichloromethane of alpha-bisabolol was used for the GC external standard (GC-ES) and the GC internal standard (GC-IS). A 9.6 mg / ml solution of alpha-bisabolol can be prepared. The column temperature can be programmed to vary from 40°C (4 min) to 200°C at a rate of 3°C / min. The injector and detector can be maintained at 200°C and 240°C, respectively. The carrier gas is N2, with a flow rate of 1.80 ml / min. A 1.0 μl volume (1.0 w / v% solution of the composition in dichloromethane) can be injected with a split ratio of 1:10. The content of alpha-bisabolol in the composition can be calculated from the percentage of its peak area relative to the total area of ​​the chromatogram (see, e.g., Cerceau et al. in Talanta, Vol. 162, Dec. 1, 2016, pp. 71-79), or can be calculated using GC / FID and a commercially available alpha-bisabolol standard (e.g., from Merck) to prepare a calibration curve and determine retention time.Alpha-bisabolol, CO2 extract, ethanol extract of chamomile, and other (naturally occurring) sources of alpha-bisabolol can be purchased commercially.

[0107] In a further preferred embodiment, the composition according to the invention comprises chamazulene as component (d), preferably in an amount of at least 0.0006% (w / w), such as at least 0.002% (w / w), for example from 0.002% (w / w) to 1% (w / w), such as from 0.002% (w / w) to 0.8% (w / w), for example from 0.003% (w / w) to 0.8% (w / w), such as from 0.003% (w / w) to 0.5% (w / w), for example from 0.004% (w / w) to 0.04% (w / w). Those skilled in the art will be aware of how to determine the amount of chamazulene in a composition using methods known in the art, for example, GC-MS and GC / FID using an Agilent 7890A gas chromatograph, an Agilent 5975C mass spectrometer equipped with a fused silica capillary HP-5 column (30 m long x 0.25 mm internal diameter, 0.25 μm film thickness), He carrier gas, and a flow rate of 1.1 ml / min, with n-hexadecane used as the internal standard. The oven temperature program starts at 70°C (hold for 1 minute), and then the column can be continuously heated to 155°C at a rate of 10°C / min. The column can then be heated to 210°C at a rate of 4°C / min and held for 1 minute. The column can then be heated to 270°C at a rate of 8°C / min and held for 2 minutes. The split ratio is 1:50, and the ionization voltage is 70 eV (for MS). Both the transfer line temperature and the injector temperature can be programmed to 280°C and 250°C, respectively (see, e.g., Ghasemi et al. in Foods 2016, 5, 56; or, to prepare a calibration curve and determine retention times, use GC / FID and commercially available chamazulene standards (e.g., from Merck / Sigma-Aldrich). Chamazulene and ethanol extracts of chamomile, as well as other (naturally occurring) sources of chamazulene, can be purchased commercially.

[0108] In a further preferred embodiment, the composition according to the invention comprises matricin as component (d), preferably in an amount of at least 0.0003% (w / w), such as at least 0.001% (w / w), for example 0.001% (w / w) to 0.5% (w / w), such as 0.001% (w / w) to 0.4% (w / w), for example 0.002% (w / w) to 0.02% (w / w). Those skilled in the art will recognize how to determine the amount of matricin in a composition using methods known in the art, for example, via GC / MS and GC / FID using an Agilent Technologies 7890B gas chromatograph equipped with a silica capillary column HP-5MS (5% diphenyl- and 95% dimethyl-polysiloxane, 30 m x 0.25 mm, 0.25 μm film thickness; Agilent Technologies, USA) and coupled to the company's inert, selective 5977A mass detector. A 3 μl sample dissolved in diethyl ether at a concentration of 1 ppm can be injected in 5:1 split mode with He carrier gas at a flow rate of 1 ml / min. The oven temperature can be programmed from 50°C for 2.25 minutes and then increased to 290°C at a rate of 4°C / min. The temperatures of the MSD transfer line, ion source, and quadrupole mass analyzer can be set to 300°C, 230°C, and 150°C, respectively. The ionization voltage can be 70 eV, and the mass range can be m / z 35-650 (for MS). GC / FID analysis can be performed under the same experimental conditions as GC / MS. The temperature of the flame ionization detector (FID) can be set to 300 °C. Data processing was performed using MSD Chem-Station, MassHunter Qualitative Analysis, and AMDIS_32 software (Agilent Technologies, USA).The retention indices of components from the analyzed samples can be experimentally determined using homologous series of C8-C20 n-alkanes as standards (see, e.g., Stanojevic et al. in Ramadan et al. in Journal of Essential Oil Bearing Plants, 19:8, 2017-2028, DOI: 10.1080 / 0972060X.2016.1224689) or can be experimentally determined using GC / FID and commercially available matricin standards (e.g., from Sigma-Aldrich) to prepare calibration curves and determine retention times. Matricin, chamomile CO2 extract, and other (naturally occurring) sources of matricin can be purchased commercially.

[0109] In a further preferred embodiment, the composition according to the present invention comprises curcumin as component (d). Preferably, the amount of curcumin (component (d) having coloring properties) is at least 0.001% (w / w), such as at least 0.003% (w / w), for example, 0.003% (w / w) to 1.5% (w / w), for example, 0.005% (w / w) to 1.2% (w / w), for example, 0.007% (w / w) to 1.1% (w / w), or for example, 0.003% (w / w) to 0.008% (w / w). Those skilled in the art will know how to determine the amount of curcumin in a composition using methods known in the art, for example, via NMR and LC-mass tandem spectrometry using curcumin (HPLC grade, Merck) in DMSO-d6 to generate a calibration curve, and 1,3,5-trimethoxybenzene can be used as an internal reference. For NMR, a Varian 600 MHz spectrometer equipped with an ID-6508 indirect probe (S / N=1084) can be used: 64 scans; 1.0 second latency; 45° pulse angle. Peak heights can be calculated for quantitative analysis (see, e.g., Goeren et al. in Food Chemistry 113 (2009) 1239-1242). Curcumin is an important component of turmeric oil. Curcumin is highly soluble in nonpolar solvents. It can be extracted from turmeric using methanol, ethanol, acetonitrile, dimethyl sulfoxide, acetone, and other polar solvents, as well as using hexane and cyclohexane. In a preferred embodiment, curcumin is part of the turmeric oil extract. For example, per part by weight of turmeric (determined by drying a sample in a drying cabinet at 105°C for 3 hours), at least 4 parts by weight of extract (preferably a vegetable oil such as rapeseed oil, olive oil, or sunflower oil), preferably 4 to 8 parts by weight, in particular 5 to 6 parts by weight of extract, are used per part by weight.Curcumin, turmeric oil, dried and ground turmeric, and other (naturally occurring) sources of curcumin can be purchased commercially.

[0110] In a further preferred embodiment, the composition according to the present invention comprises beta-caryophyllene as component (d). Preferably, the amount of beta-caryophyllene is at least 0.001% (w / w), e.g., at least 0.003% (w / w), e.g., 0.003% (w / w) to 1.5% (w / w), e.g., 0.005% (w / w) to 1.2% (w / w), e.g., 0.007% (w / w) to 1.2% (w / w), or 0.007% (w / w) to 0.1% (w / w). Beta-caryophyllene is a constituent of clove oil and Eucalyptus globulus oil. Those skilled in the art will know how to determine the amount of beta-caryophyllene in a composition using methods known in the art, for example, via GC / MS and GC / FID using an Agilent 6890 chromatograph coupled to an Agilent 5973N selective mass detector operated at 250° C. using an HP-5MS capillary column (5% phenyl-95% dimethylpolysiloxane, 30 m×0.25 mm×0.25 μm) for separation. For quantitation, an Agilent 7890A chromatograph equipped with a flame ionization detector (FID) operated at 280°C can be used, and beta-caryophyllene can be quantified using electronic integration of the FID signal by dividing the area of ​​each component by the total area (see, e.g., Santos et al in Phytomedicine Plus 1 (2021) 100100), or using GC / FID and a commercially available beta-caryophyllene standard (e.g., from Sigma-Aldrich) to prepare a calibration curve and determine retention times. In a preferred embodiment, beta-caryophyllene is a part of a clove oil extract (5% to 12% or a part of a rosemary oil extract. At least 4 parts by weight of extract (preferably a vegetable oil such as rapeseed oil, olive oil or sunflower oil), preferably 4 to 8 parts by weight, in particular 5 to 6 parts by weight, of the extract are used per part by weight of the dry weight of cloves or rosemary (determined by drying a sample at 105°C for 3 hours in a drying cabinet).Beta-caryophyllene (e.g., from TCI Chemicals), clove oil or rosemary oil, and dried and optionally ground cloves or rosemary, as well as other (naturally occurring) sources of beta-caryophyllene, can be purchased commercially. In a further preferred embodiment, the amount of oil extract from cloves or Eucalyptus globulus ranges from 0.1% (w / w) to 5% (w / w), more preferably from 0.1% (w / w) to 3% (w / w), even more preferably from 0.1% (w / w) to 1% (w / w), for example, from 0.15% (w / w) to 0.7% (w / w).

[0111] In a further preferred embodiment, the composition according to the invention comprises ursolic acid as component (d), preferably in an amount of at least 0.001% (w / w), such as at least 0.003% (w / w), for example, from 0.003% (w / w) to 1.5% (w / w), such as from 0.005% (w / w) to 1.2% (w / w), for example, from 0.007% (w / w) to 0.1% (w / w). Ursolic acid, sage oil, fresh or dried sage, and other (naturally occurring) sources of ursolic acid (e.g., Malus domestica, Salvia triloba, Thymus vulgaris, Thymus serpyllum, Lavandula latifolio, Rosmarinus officinalis) can be purchased commercially. Those skilled in the art will know how to determine the amount of ursolic acid in a composition using methods known in the art, such as via HPLC using a Shimadzu LC-1 0AD pump system equipped with a Shimadzu SPD-M10A photodiode array detector, using a reversed-phase column (Shimpack CLC-ODS(M) 4.6 mm x 15 cm, 5 μm particle size) with a detection wavelength set at 206 nm. Elution rate 0.5 ml / min. A:B solvent system: A - acetonitrile; B - 1.25% HPO aqueous solution (A:B = 86:14 (v / v), injection volume 20 μl (ursolic acid (e.g., from SigmaAldrich) is used for preparation of the calibration curve) (see, e.g., Silva et al in Molecules 2008, 13, 2482-2487; DOI: 10.3390 / molecules13102482). Ursolic acid, sage oil, and dried and optionally ground sage, as well as other (naturally occurring) sources of ursolic acid, can be purchased commercially. In a preferred embodiment, the ursolic acid is part of a sage oil extract.At least 4 parts by weight of extract (preferably with a vegetable oil such as rapeseed, olive or sunflower oil), preferably 4 to 8 parts by weight, in particular 5 to 6 parts by weight, are used per part by weight of dry weight of sage (determined by drying a sample in a drying cabinet at 105°C for 3 hours). In another preferred embodiment, the amount of sage oil extract is in the range of 0.1% (w / w) to 5% (w / w), more preferably 0.1% (w / w) to 3% (w / w), even more preferably 0.1% (w / w) to 1% (w / w), for example 0.15% (w / w) to 0.7% (w / w).

[0112] In a further preferred embodiment, the composition according to the present invention comprises eugenol (CAS 97-53-0) as component (d). Preferably, the amount of eugenol is at least 0.001% (w / w), such as at least 0.003% (w / w), for example, 0.003% (w / w) to 1.5% (w / w), for example, 0.005% (w / w) to 1.2% (w / w), for example, 0.007% (w / w) to 0.1% (w / w). The clove oil comprises 65% to 85% eugenol. In a preferred embodiment, the composition comprises clove oil, preferably, wherein the amount of clove oil in the composition is 0.0015% (w / w) to 1.76% (w / w). Those skilled in the art will be aware of how to determine the amount of eugenol in a composition using methods known in the art, for example, a Shimadzu GC-2010 gas chromatograph equipped with an FID and a DB-5 fused silica column (30 m x 0.25 mm internal diameter, 0.25 μm film thickness, Agilent). The oven temperature is 80°C for 2 minutes, then heated from 80°C to 230°C at a rate of 6°C / min, and held at 230°C for 2 minutes. The injector and detector temperatures can be 230°C, the carrier gas is N2, and the flow rate is 24 ml / min. The sample (0.1% in absolute ethanol) can be injected into the GC with a split ratio of 1:20. Methyl salicylate can be used as an internal standard (see, e.g., Guan et al in Food Chemistry 101 (2007) 1558-1564), or GC / FID and commercially available eugenol standards (e.g., from Merck) can be used to prepare calibration curves and determine retention times.

[0113] In a further preferred embodiment, the composition according to the invention comprises camphor (CAS 76-22-2) as component (d). Preferably, the amount of camphor is at least 0.001% (w / w), such as at least 0.003% (w / w), for example 0.003% (w / w) to 1.5% (w / w), for example 0.005% (w / w) to 1.2% (w / w), for example 0.007% (w / w) to 0.1% (w / w).

[0114] Those skilled in the art will recognize how to determine the amount of camphor in a composition using methods known in the art, for example, via GC / MS and GC / FID using cyclodecanone as an internal reference using a fused silica capillary column (HP-Innowax, 60 m x 0.25 mm internal diameter, 0.25 μm film thickness) and an Agilent model 6890 Series Plus gas chromatograph coupled with a CTC Combi PAL autosampler and an Agilent 5973N mass selective detector or FID detector. Temperature program: hold at 45°C for 1 minute, ramp to 180°C at 5°C / min, ramp to 240°C at 25°C / min, and hold for 5 minutes. The temperatures of the injection port, ion source, quadrupole, and interface can be set to 240°C, 230°C, 150°C, and 250°C, respectively. Split / splitless injection port (1 μl, splitless), carrier gas He, flow rate 1.0 ml / min. Data acquisition and analysis can be carried out using the standard software provided by the manufacturer.For quantification, the peak area ratio of analyte to internal standard cyclodecanone can be calculated as a function of substance concentration (see, for example, Walch et al. in Chemistry Central Journal 2011, 5:44);Or use GC / FID and commercially available camphor standard (for example, SigmaAldrich) to prepare calibration curve and determine retention time.

[0115] In a further preferred embodiment, the composition according to the invention comprises cineole (CAS 470-82-6) as component (d). Preferably, the amount of cineole is at least 0.001% (w / w), such as at least 0.003% (w / w), for example, from 0.003% (w / w) to 1.5% (w / w), such as from 0.005% (w / w) to 1.2% (w / w), for example, from 0.007% (w / w) to 0.1% (w / w). A person skilled in the art will know how to determine the amount of cineole in a composition using methods known in the art, for example, via GC using an Agilent 7890B / 7000D GC-MS / MS instrument. A 1 μl sample can be injected into an HP-5 ms fused silica capillary column (30 m, 0.25 mm internal diameter, 0.25 μm film thickness) with a split ratio of 1:5 at a flow rate of 2.25 ml / min using He as the carrier gas. The inlet temperature can be set to 250°C. Program: initial temperature 100°C (held for 1 min) can be increased to 280°C at a rate of 25°C / min and held constant for 1.5 min. The total run time can be 23.7 min. MS conditions were as follows: electron impact ionization (EI) mode; transfer line temperature, 280 °C; ionization energy, 70 eV; ion source temperature, 230 °C; MS quadrupole temperature, 150 °C. A weighed amount of cineole in n-hexane was used to prepare the calibration curve (see, e.g., Sa et al. in Biomedical Chromatography 2021;35:e5080). Alternatively, GC / FID and a commercially available cineole standard (e.g., from Merck) were used to prepare the calibration curve and determine retention times. Cineole is the major component of Eucalyptus (Eucalyptus) (70%–90% of eucalyptus oil).

[0116] In a further preferred embodiment, the composition according to the present invention comprises thujone as component (d). Thujone occurs primarily in the form of two diastereomers, (-)-α-thujone and (+)-β-thujone. Preferably, the amount of thujone is at least 0.001% (w / w), such as at least 0.003% (w / w), for example, 0.003% (w / w) to 1.5% (w / w), for example, 0.005% (w / w) to 1.2% (w / w), for example, 0.007% (w / w) to 0.1% (w / w). Those skilled in the art will know how to determine the amount of thujone in a composition using methods known in the art (see, e.g., Walch et al. in Chemistry Central Journal 2011, 5:44, supra) or using GC / FID and commercially available thujone standards (e.g., from SigmaAldrich) to prepare a calibration curve and determine retention times.

[0117] In a further preferred embodiment, the composition according to the present invention comprises cuminaldehyde (CAS 122-03-2) as component (d). Preferably, the amount of cuminaldehyde is at least 0.001% (w / w), such as at least 0.003% (w / w), for example, 0.003% (w / w) to 1.5% (w / w), for example, 0.005% (w / w) to 1.2% (w / w), for example, 0.007% (w / w) to 0.1% (w / w). Those skilled in the art will know how to determine the amount of cuminaldehyde in a composition using methods known in the art, for example, using an Agilent GC 7890A gas chromatograph equipped with an FID and an HP-5 capillary column (30 m x 0.25 mm, 0.25 μm film thickness). The initial oven temperature can be held at 50 °C for 3 minutes and then increased to 120 °C at a heating rate of 3 °C / min; the column temperature can then be programmed from 120 °C to 250 °C at a heating rate of 5 °C / min and held at this temperature for 5 minutes, with N2 as the carrier gas and a flow rate of 2 ml / min. The injector and detector temperatures can be adjusted to 280 °C and 300 °C, respectively. The sample size is 1.0 μl, and the split ratio is 1:10 (see, e.g., Bahman et al. in J Oleo Science, 63, (7), 741-746 (2014)). Cuminaldehyde (e.g., cuminaldehyde ≥ 98%, FCC, FG, from Merck) can be used to prepare the calibration curve.

[0118] In one preferred embodiment, the composition according to the invention comprises, as component (d), at least one compound selected from the group consisting of alpha-bisabolol, matricin, and chamazulene. In another preferred embodiment, the composition according to the invention comprises, as component (d), at least one compound selected from the group consisting of alpha-bisabolol, matricin, and chamazulene, and the further component of chamomile extract or chamomile oil. In another preferred embodiment, the composition according to the invention comprises, as component (d), curcumin. In another preferred embodiment, the composition according to the invention comprises, as component (d), curcumin and the further component of turmeric oil extract.

[0119] The anti-inflammatory component (d) is, in one embodiment, added in the form of an oil or extract derived from chamomile (Matricaria recutita), clove (Clove japonica), rosemary (Salvia rosmarinus), eucalyptus globulus, turmeric (Curcuma longa), and sage (Salvia officinalis), with chamomile being particularly preferred.

[0120] Those skilled in the art will appreciate that the concentrations of components in essential oils or extracts of herbs may vary depending on the geographic origin of the plant, the plant variety, and the processing of the plant parts, but these substances are present in the oils derived from these plants, or in the non-polar solvent or alcohol and / or water extracts, in amounts sufficient to achieve the desired effect.

[0121] Further components (in a preferred embodiment, further component (e)) In addition to the essential components (a) to (d), oral care compositions may contain further additives, such as sources of vasodilatory components, antioxidants, emulsifiers, etc. If the product of the additional component (e) for preparing the composition according to the present invention contains components of groups (a) to (d), the amount of these components in such a product is assigned to the corresponding group (a) to (d) when calculating the various amounts. For example, propolis can be one additional component (e) (see e1). However, if the propolis extract product also contains water or ethanol (e.g., an ethanol extract of propolis), the amount of water or ethanol is subtracted from the amount of the propolis product used and assigned to group (a) (see, e.g., Example 1).

[0122] In some cases, additional components can be assigned to several subcategories of (e). For example, salts such as stannous fluoride contain metal ions (e22) and fluoride anions (e14). However, this is irrelevant because only the total amount of other additives is relevant in (e) (i.e., the amount of stannous fluoride is counted); or, a compound (e) may be mentioned in more than one subgroup (e), but is counted only once when assessing the amount of compound (e) in the composition; for example, lactic acid is a hydroxy acid (e16), but also has a moisturizing effect (e7), but is counted only once when assessing the amount of component (e).

[0123] For clarity, if a component of groups (a)-(d) has, in addition to the essential properties required for a)-d), a further property that can be assigned to a "further component (e)," the amount of the essential component counts only toward the amount of essential components (a)-(d) in the overall composition. For example, propylene glycol is a protic solvent. However, it also has a moisturizing and preservative effect. In compositions according to the present invention, the level of propylene glycol (if present) is attributed to the protic solvent (a), not to the level of "further components" (e), which may also include other preservatives and moisturizers.

[0124] The additional component (such as (e)) is either a component accompanying compounds (a) to (d) (e.g., a carbomer product such as Carbomer Gel pH 6.5 NRF S43 contains, next to Carbomer 35,000, additional additives, i.e., trometamol (tris(hydroxymethyl)aminomethane (TRIS)) (buffer), sodium edetate (sodium ethylenediaminetetraacetate (EDTA)) (complexing agent), propylene glycol (protic solvent), and water (protic solvent)); or the additional component (such as (e)) is added to the composition according to the invention. Thus, those skilled in the art will understand that the additional component (such as (e)) encompasses any component accompanying as an auxiliary, solvent, or other additive in a commercially available product as of the filing date of this application, which is used to provide a compound of group (a), (b), (c), (d), or optionally (e) to the composition according to the invention.

[0125] Those skilled in the art will understand that up to 10% of the compositions according to the invention can correspond to compounds that are not compounds of groups (a) to (d) as defined herein. Thus, those skilled in the art will understand that, although a definitive list of such additives is not required, additives available as of the filing date of this application can be added to the oral care compositions of the invention, as long as the combination of such additional component (e) does not result in a formulation that no longer falls within the scope of the invention. Those skilled in the art will understand that the addition of up to 10% of additional components (such as (e)) can positively enhance aspects of the compositions according to the invention, for example, the good flow behavior of the gels according to the invention can be further improved, or the addition of such components can improve the acceptability of the composition by users (e.g., better taste, different color, better sensory experience of the composition), or even the additional provision of beneficial components for the gums, such as vitamins or oral-strengthening polyols (e.g., dexpanthenol), can improve the already novel and inventive positive effects of the compositions according to the invention.

[0126] Thus, in one preferred embodiment, the composition according to the invention comprises one or more further components (preferably (e)), wherein the total amount of said further components (preferably (e)) is 10% (w / w) or less. In yet another preferred embodiment, the composition comprises at least one antioxidant, preferably one or more catechins, as further components (preferably (e)), wherein the total amount of all further components (e) is 10% (w / w) or less. Non-limiting, but preferred, examples of further components are the compounds listed in subgroups (e1) to (e22). In yet another preferred embodiment, the composition comprises one or more additional components (e) selected from the group consisting of (e1), (e2), (e3), (e4), (e5), (e7), (e8), (e9), (e12), (e14), (e15), (e16), (e18), (e21), and (e22). In yet another preferred embodiment, (e) in the composition consists of one or more compounds selected from the group consisting of (e1), (e2), (e3), (e4), (e5), (e7), (e8), (e9), (e12), (e14), (e15), (e16), (e18), (e21), and (e22). In a more preferred embodiment, the composition comprises at least one compound of group (e4), even more preferably at least one catechin selected from the group consisting of C, EC, ECG, EGC, and EGCG.Preferred components (e1) are lotus extract, propolis or propolis extract, chamomile oil or extract, clove oil or extract, Mentha piperita oil or extract, Mentha arvensis oil or extract, turmeric oil or extract, sage oil or extract, Eucalyptus globulus oil or extract, Mentha spicata oil or extract, Micromeria fruticosa oil or extract, Artemisia dracunculus oil or extract, Origanum vulgare oil or extract, Rosmarinus officinalis oil or extract, Thymus oil or extract, Ocimum basilicum oil or extract, Origanum majorana oil or extract, majorana oil or extract, Theobroma cacao extract, Camellia sinensis extract, and in a preferred embodiment, the extract is provided in the form of a lyophilisate.

[0127] In a preferred embodiment, the composition contains one or more (e1) aprotic solvents, such as plant oils and extracts, and extracts of animal origin, such as propolis or propolis extract (propolis is produced by honeybees and has antibiotic, viral, and fungal properties). Propolis is a mixture of many different substances. It consists of approximately 55% natural resin and pollen balm, approximately 30% wax, approximately 5% pollen, and approximately 10% essential oil derived from flower buds and salivary secretions. Propolis resign and pollen balm are rich in flavonoids, more preferably one or more flavonoids selected from the group consisting of chrysin, galangin, pinocembrin, pinobanksin acetate, prenylflavonoids, isonymphaeol-B, nymphaeol-A, nymphaeol-B, and nymphaeol-C. In addition to flavonoids, propolis also contains gums, phenols (cinnamic acid, coumaric acid, caffeic acid, ferulic acid, isoferulic acid) and their esters, as well as polysaccharides not included in group (c). Due to the common presence of beneficial oral compounds in propolis, in a preferred embodiment, the composition contains 0.005% (w / w) to 2% (w / w), e.g., 0.01% (w / w) to 2% (w / w), or 0.005% (w / w) to 1% (w / w), or 0.01% (w / w) to 0.8% (w / w). Propolis can be used as is or in the form of a pre-dissolved extract. In such cases, it is sufficient to provide the amount of propolis added to the formulation to prepare the composition according to the invention. While quantitative determination of the various components of propolis is not necessary, the amount of added propolis is considered when calculating the total amount of component (e). When propolis extract is used, of course, the relevant solvents of group (a) must be subtracted from the amount of propolis extract and added to group (a). Propolis extract is commercially available (e.g., from Hoyer GmbH).

[0128] In a preferred embodiment, the composition comprises lotus extract, more preferably, the composition comprises lotus extract, wherein the amount of lotus extract ranges from 0.1% (w / w) to 5% (w / w), more preferably from 0.4% (w / w) to 2% (w / w). Lotus extract is rich in vitamins (especially vitamin C in the root and high amounts of vitamin A overall), minerals, especially iron, copper, manganese, zinc, and potassium compounds, armepavin, fatty acids, protein, phosphorus, and linoleic acid, and has a positive effect on skin tone. Because the high level of potassium in lotus root dilates blood vessels, thereby promoting blood circulation, lotus extract also has a vasodilatory effect. It is preferably an extract derived from lotus root tissue. It is also preferably an aqueous extract or an extract of water and up to 80% ethanol. Generally, like the other aqueous and / or alcoholic extracts described herein, lotus extract can be freeze-dried, and the resulting powder can be used to prepare the composition according to the present invention. Lotus extracts typically contain at least 4 parts by weight of extract (preferably 4-8 parts by weight, especially 5-6 parts by weight) per part by weight dry weight of lotus (determined by drying a sample at 105°C in a drying cabinet for 3 hours). Lotus extracts are commercially available in various formulations (powder as a freeze-dried extract or liquid as an extract), for example from Ruschin.

[0129] In the context of the present invention, vegetable oils and their components are considered aprotic solvents. (Plant) oils or extracts may also contain trace amounts of specific aprotic solvents selected from the group consisting of acetonitrile, dimethyl sulfoxide, acetone, and other polar solvents, as well as alkanes such as hexane and cyclohexane, and halogenated alkanes such as dichloromethane, which may be required for the preparation of plant extracts or plat oils. Preferably, the amount of such specific protic solvents, especially hexane or dichloromethane, in the composition is less than 0.002% (w / w).

[0130] The vegetable oil contains 5% to 80% linolenic acid and is cholesterol-free. Most preferably, the oil is liquid at 20°C (a liquid is a nearly incompressible fluid that conforms to the shape of its container but maintains a nearly constant volume independent of pressure). In a preferred embodiment, the composition comprises one or more vegetable oils or vegetable extracts, preferably chamomile, clove, rosemary, turmeric, sage, rapeseed (Brassica napus), olive (Olea europaea), sunflower (Helianthus annuus), or other vegetable oils. The composition according to the present invention comprises one or more vegetable oils or vegetable extracts selected from the group consisting of vegetable oils derived from Mentha annuus, peppermint, and lotus (if a component of the vegetable oil is a component of group (d), the amount of this component is listed in group (d) and is subtracted from the amount of the vegetable oil which is the further component (e)), preferably wherein the total amount of vegetable oil is 0.1% (w / w) to 8% (w / w), more preferably 0.1% (w / w) to 5% (w / w), even more preferably 0.1% (w / w) to 3% (w / w), for example 0.15% (w / w) to 0.1% (w / w). Curcumin is an important component in turmeric oil. In a further preferred embodiment, the composition according to the present invention comprises turmeric oil. The amount of this oil is preferably in the range of 0.1% (w / w) to 5% (w / w), more preferably 0.2% (w / w) to 3% (w / w). Beta-caryophyllene can be found, for example, in clove oil and Eucalyptus globulus oil. In a further preferred embodiment, the composition according to the present invention comprises clove oil or Eucalyptus globulus oil. The amount of either of these oils is preferably in the range of 0.1% (w / w) to 5% (w / w), more preferably 0.2% (w / w) to 3% (w / w). Ursolic acid can be found, for example, in sage oil (Salvia officinalis). In a further preferred embodiment, the composition according to the present invention comprises sage oil. The amount of this oil is preferably in the range of 0.1% (w / w) to 5% (w / w), more preferably 0.2% (w / w) to 3% (w / w). Eugenol is the main component of clove oil.In a further preferred embodiment, the composition according to the present invention comprises sage oil. The amount of this oil is preferably in the range of 0.1% (w / w) to 5% (w / w), more preferably 0.2% (w / w) to 3% (w / w). Alpha-bisabolol, matricin, and chamazulene are important compounds in chamomile extract / oil. In a further preferred embodiment, the composition comprises a chamomile extract, preferably a CO2 extract or an ethanol extract. The amount of this CO2 extract or ethanol extract is preferably in the range of 0.1% (w / w) to 5% (w / w), more preferably 0.2% (w / w) to 3% (w / w). An important constituent of various vegetable oils is menthol (2-isopropyl-5-methylcyclohexanol). Menthol is, inter alia, an antiseptic. Menthol is commercially available (e.g., from Roth). It is found in Mentha oils, such as peppermint oil (Mentha piperita), wild mint (Mentha americana), or mint oil, as well as in other oils such as Micromeria fruticosa, tarragon (Artemisia duraunculus), basil (Basil basilicas), marjoram (Origanum majorana), oregano (Origanum vulgare), and rosemary. Menthol is a major constituent of other genera and species of the mint family (Labiatae), such as Rosmarinus officinalis, sage (Salvia), and thyme (Thymus vulgaris). In a preferred embodiment, the composition comprises peppermint oil or mentha oil. Both can be produced, for example, by steam distillation of peppermint or wild mint plants, respectively. Menthol, peppermint oil, or mentha leaf oil, and other oils from the mint family, are commercially available (e.g., Roth and Essence-pur GmbH).In another preferred embodiment, the amount of peppermint oil, common mentha leaf oil, common mint, Micromeria fruticosa, tarragon, basil, marjoram, oregano, rosemary, sage, or thyme oil, or a combination thereof, in the composition, more preferably the amount of peppermint oil, common mentha leaf oil, or common mentha oil, is in the range of 0.001% (w / w) to 5% (w / w), more preferably 0.1% (w / w) to 3% (w / w), even more preferably 0.1% (w / w) to 1% (w / w), for example, 0.15% (w / w) to 0.7% (w / w). In a further preferred embodiment, the composition contains common mentha oil, preferably leaf oil. Common mentha oil, common mentha extract, and oils and extracts of parts of the plant (e.g., steam-distilled products) are commercially available. The amount of this oil in the composition is preferably 0.001% (w / w) to 2.5% (w / w), more preferably 0.02% (w / w) to 0.5% (w / w). In a preferred embodiment, the amount of menthol in the composition is 0.0001% (w / w) to 2% (w / w), more preferably 0.1% (w / w) to 2% (w / w). If any of these oils is part of the composition, a person skilled in the art can easily calculate the amount of menthol in the oil using the information provided by the supplier. Alternatively, one skilled in the art can determine the amount of menthol in an oil or composition using HPLC methods known in the art, for example, a chromatographic system with an autoinjector, a Waters 2414 refractive index detector, an Inertsil ODS 3V (4.6 mm × 250 mm, 5 μm) column, a 2.5 mg / 5 mg menthol stock dilution, an injection volume of 100 μl, and water:methanol (30:70 v / v) as the mobile phase (see, e.g., Shaikh in J Pharm Bioallied Sci. 2010 Oct-Dec; 2(4): 360-364). Group e1 encompasses all additional substances present in the oil or extract in addition to the compounds of groups (a)-(d). In a preferred embodiment, a tea extract is part of a composition to provide specific catechins (see e4—antioxidants).

[0131] In a preferred embodiment, the composition comprises one or more (e2) buffer compounds (resulting in a combination of buffer compounds) that adjust and / or stabilize the pH value in the range of 6 to 7.5, more preferably in the range of 6.5 to 7.5, and that are typically present in this pH range (either in the form of a weak acid and its corresponding base, or vice versa, in the form of a weak base and its corresponding acid). Those skilled in the art will recognize that, depending on the nature of the compound, adjusting the pH of the composition in the presence of the buffer compound may require the addition of a strong acid or base that reduces or increases the pH (e.g., HCl, NaOH, H2SO4, H3PO4, etc.). Such pH-adjusting compounds are also encompassed by the term buffer. In a preferred embodiment, the composition comprises a phosphate buffer selected from the group consisting of TRIS, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), a buffer containing an alkali dihydrogen phosphate and an alkali hydrogen phosphate, for example, potassium dihydrogen phosphate or sodium dihydrogen phosphate, optionally with various counterparts (e.g., phosphate buffer according to Sorensen (KH2PO4 / Na2HPO4), KH2PO4 and NaOH, a combination of an alkali chloride salt with an alkali dihydrogen phosphate and / or dihydrogen phosphate (e.g., PBS: NaCl, Na2HPO4KCl, and KH2PO4), a carbonate buffer (e.g., sodium bicarbonate, potassium bicarbonate, ammonium bicarbonate), Preferably, the term alkaline in combination with buffer / buffer component refers to an alkaline ion selected from Na and K, preferably wherein the total amount of buffer components in the composition is 0.05% (w / w) to 2% (w / w). In a further preferred embodiment, the composition comprises a buffer selected from the group consisting of TRIS, HEPES, sodium bicarbonate, potassium bicarbonate KH2PO4 / Na2HPO4, sodium citrate (and optionally citric acid), and PBS, even more preferably from the group consisting of TRIS, sodium carbonate, and PBS.In a preferred embodiment, the composition comprises TRIS, preferably wherein the amount of TRIS is 0.03% (w / w) to 0.9% (w / w), preferably 0.3% (w / w) to 0.9% (w / w). In another preferred embodiment, the composition comprises sodium bicarbonate, preferably wherein the amount of sodium bicarbonate is 0.01% (w / w) to 0.9% (w / w), preferably 0.01% (w / w) to 0.3% (w / w). In another preferred embodiment, the composition comprises PBS, preferably wherein the amount of PBS (8.184 g NaCl, 1.8 g NaHPO, and 0.3 g KHPO per 1000 ml of buffer solution) is 0.01% (w / w) to 0.9% (w / w), preferably 0.01% (w / w) to 0.3% (w / w).

[0132] In a preferred embodiment, the composition includes one or more (e3) chelating agents (chemical compounds capable of forming stable complexes with metal ions by coordinating with them through multiple sites). In a preferred embodiment, the composition includes one or more chelating agents selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), ethylene glycol tetraacetic acid (EGTA), ethylenediamine, citric acid, mercaptodicarboxylic acid, and triethanolamine (TEA), preferably, wherein the total amount of the one or more chelating agents in the composition is in the range of 0.001% (w / w) to 5% (w / w), more preferably 0.005% (w / w) to 0.5% (w / w). In a preferred embodiment, the chelating agent is EDTA. In a further preferred embodiment, the composition according to the present invention includes a complexing agent. The amount of the complexing agent is preferably in the range of 0.005% (w / w) to 0.5% (w / w).

[0133] In a preferred embodiment, the composition comprises one or more (e4) antioxidants. In a preferred embodiment, the composition comprises L-ascorbic acid or a derivative thereof (e.g., sodium ascorbyl phosphate), dibutylhydroxytoluene, butylhydroxyanisole, superoxide dismutase, a carotenoid, astaxanthin, rutin or a derivative thereof, hesperidin, quercetin, a catechin [preferably selected from the group consisting of catechin (C), epicatechin (EC), epigallocatechin (EGC), or a derivative thereof including a saccharide derivative and an ester with gallic acid or a gallic acid derivative (preferably ECG or EGCG), more preferably at least one catechin is selected from the group consisting of EC, ECG, EGC, and EGCG]; a gallic acid or a derivative thereof, preferably an ether of a fatty acid and gallic acid; allantoin (N-(2,5-dioxoimidazolidin-4-yl)urea) and a derivative thereof, preferably aluminum chlorohydroxyallantoinate, aluminum chlorohydroxyallantoinate propylene glycol, aluminum dihydroxyallantoinate, Allantoin calcium pantothenate, allantoin glycyrrhetinic acid, allantoin ascorbate, allantoin N-acetyl-DL-methionine, allantoin zinc undecylenate, allantoin ethyl p-aminobenzoate, glutathione or its derivatives, glutathione, β-carotene or its derivatives, ubiquinol, polyphenols, hydrangea, turmeric, star anise, echinacea, scutellaria root, hypericum perforatum, chinese gallnut, geranium herb, rice, rice bran, comfrey, zanthoxylum piperitum, lamiaceae plants, peony root, soybeans, "natto" (soybeans fermented with their own bacteria), tea leaves, cloves, loquat, peony, horse chestnut, saxifrage, rooibos, rosemary, spirulina, chlorella and dunaliella, bilirubin, cholesterol, tryptophan, histidine, thiotaurine, and hypotaurine, preferably wherein the total amount of the one or more antioxidants is 0.001% (w / w) to 5% (w / w).

[0134] In a preferred embodiment, the composition comprises one or more antioxidants selected from the group consisting of ascorbic acid, sodium ascorbyl phosphate, catechin, allantoin (or its allantoinate form), and limonene, more preferably selected from the group consisting of EC, ECG, EGC, and EGCG, allantoin, allantoinate, and limonene.

[0135] In a preferred embodiment, the composition comprises allantoin or allantoinate, preferably wherein the amount of allantoin or allantoinate is 0.001% (w / w) to 5% (w / w), more preferably 0.001% (w / w) to 2% (w / w).

[0136] In a preferred embodiment, the composition comprises ascorbic acid or sodium ascorbyl phosphate, preferably in an amount of 0.001% (w / w) to 5% (w / w), more preferably 0.001% (w / w) to 2% (w / w).

[0137] The presence of catechins was observed (without being bound by explanation, catechins can be antioxidant components by activating glutathione peroxidase, as well as vasodilator components), and the compositions according to the present invention showed further enhancement in gum health and inhibition of plaque formation. Thus, a preferred embodiment relates to a composition comprising at least one catechin, preferably a catechin derived from green tea or cocoa, more preferably selected from the group consisting of EC, ECG, EGC, and EGCG; or selected from the group consisting of C and EC.

[0138] The determination of catechin (c) and epicatechin (EC), as well as other catechins such as EGC, ECG, and EGCG, was performed using calibration standard solutions of the respective catechins, e.g., gradient elution (solution A: 0.1 ml orthophosphoric acid dissolved in 900 ml HPLC-grade water, the volume was brought to 1000 ml with water, filtered through a 0.45 μm membrane filter, and degassed in a sonicator for 3 min; solution B: acetonitrile) with a flow rate of 1.0 ml / min, an operating temperature of 30 °C, and detection at 280 nm with a UV-visible detector. The mobile phase was gradient elution: 11% B at 0.01 min; 25% B at 30 min; 100% B at 35-39 min; and B at 40-50 min. Calibration curves can be prepared and performed using HPLC methods known in the art (see, for example, Raju et al. in Int. Sch. Res. Notices 2014; 2014; 628196) using an HPLC system (Shimadzu, 2010 CHT) consisting of a quaternary pump with a vacuum degasser, a thermostatted column compartment, an autosampler, and a UV detector, and a reverse-phase column (TARGA, C18, 5 μm, 250 × 4.6 mm) (flowed using 11%). Catechins for preparing calibration curves are available, for example, from Merck, SigmaAldrich, and / or Roth.

[0139] In a preferred embodiment, the amount of the catechin component in the composition is 0.001% (w / w) to 5% (w / w), such as 0.2% (w / w) to 5% (w / w), more preferably 0.5% (w / w) to 3.5% (w / w), even more preferably 1.8% (w / w) to 2.5% (w / w) (e.g., 2.2% (w / w) to 2.4% (w / w)). Catechins, dried tea, tea extracts, dried cocoa, and cocoa extracts are commercially available. In a preferred embodiment, the composition comprises EGCG; more preferably, the amount of EGCG is 0.2% (w / w) to 5% (w / w), even more preferably 0.2% (w / w) to 2% (w / w). In another preferred embodiment, the composition comprises EC; more preferably, wherein the amount of EC is 0.03% (w / w) to 0.5% (w / w), such as 0.03% (w / w) to 0.85% (w / w), even more preferably 0.03% (w / w) to 0.17% (w / w). In yet another preferred embodiment, the composition comprises ECG; more preferably, wherein the amount of ECG is 0.03% (w / w) to 0.85% (w / w), such as 0.05% (w / w) to 1.5% (w / w), even more preferably 0.05% (w / w) to 0.3% (w / w). In yet another preferred embodiment, the composition comprises EGC; more preferably, wherein the amount of EGC is 0.03% (w / w) to 0.85% (w / w), such as 0.09% (w / w) to 2.3% (w / w), even more preferably 0.09% (w / w) to 0.46% (w / w). In yet another preferred embodiment, the composition comprises a combination of EC, ECG, EGC, and EGCG, preferably, wherein the amount of EGCG is 0.2% (w / w) to 1% (w / w), the amount of EC is 0.03% (w / w) to 0.17% (w / w), the amount of ECG is 0.05% (w / w) to 0.3% (w / w), and the amount of EGC is 0.09% (w / w) to 0.46% (w / w).

[0140] In another preferred embodiment, the composition comprises C and EC. In a preferred embodiment, the composition comprises C; more preferably, wherein the amount of C is 0.03% (w / w) to 5% (w / w), even more preferably 0.05% (w / w) to 1% (w / w). In another preferred embodiment, the composition comprises C and EC, wherein the amount of C is 0.05% (w / w) to 1% (w / w) and the amount of EC is 0.05% (w / w) to 4.95% (w / w).

[0141] In another preferred embodiment, the composition comprises limonene, more preferably wherein the amount of limonene is between 0.001% (w / w) and 5% (w / w), more preferably between 0.001% (w / w) and 2% (w / w).

[0142] In a preferred embodiment, the composition contains one or more preservatives (e5). In a preferred embodiment, the one or more preservatives are selected from the group consisting of benzoic acid and its Na, K, magnesium, and calcium salts, particularly the Na salt; propionic acid and its Na, K, magnesium, and calcium salts; salicylic acid and its Na, K, magnesium, and calcium salts; phenylmethanol; phenoxyethanol; sorbitan caprylate; caprylyl glycol; and parabens (e.g., methylparaben or propylparaben), preferably in a total amount of 0.01% (w / w) to 0.5% (w / w). In one embodiment, the preservative is methylparaben.

[0143] In a preferred embodiment, the composition comprises one or more (e6) humectants (different from the compounds of group (a), (b), or (c)). In a preferred embodiment, the one or more, more preferably one, humectant is selected from the group consisting of aloe vera gel, alpha hydroxy acids (e.g., lactic acid), glyceryl triacetate, LiCl, polymeric polyols (e.g., polydextrose), polyethylene glycol (PEG), sodium hexametaphosphate, maltitol, urea, and castor oil (a vegetable oil expressed from the castor bean), preferably in an amount of 0.1% (w / w) to 10% (w / w) in total.

[0144] In a preferred embodiment, the composition comprises one or more (e7) flavorings. In a preferred embodiment, the composition comprises one or more flavorings selected from the group consisting of wintergreen, cassia, parsley oil, marjoram, lemon, orange, propenylguaethol, heliotropin, 4-cis-heptenal, diacetyl, methyl-p-tert-butylphenylacetate, menthol, methyl salicylate, 1-ethylone halicylate a-irison, methyl cinnamate, ethyl cinnamate, butyl cinnamate, ethyl butyrate, ethyl acetate, methyl anthranilate, iso-amyl acetate, iso-amyl butyrate, allyl caproate, thymol, cinnamyl alcohol, octanol, octanal, decanol, decanal, phenylethyl alcohol, benzyl teral alcohol alcohol), linalool, limonene, citral, neral, geranial, geraniol, nerol, maltol, ethyl maltol, anethole, dihydroanethole, carvone, menthone, beta-damascenone, ionone, gamma-decalactone, gamma-nonalactone, and y-undecalactone, and the total amount of the one or more flavors is preferably 0.001% (w / w) to 5% (w / w), more preferably 0.01% (w / w) to 4% (w / w).

[0145] In a preferred embodiment, the composition comprises one or more (e8) vitamins. In one embodiment, the composition comprises one or more vitamins selected from the group consisting of vitamin A, vitamin B (such as vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B7 (biotin), vitamin B9 (folic acid), and vitamin B12 (cobalamin), vitamin C (ascorbic acid), vitamin D (such as vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), vitamin E (such as α-, β-, γ-, and δ-tocopheryl, and α-, β-, γ-, and δ-tocotrienol). TIFF2025529924000005.tif54128 or any of the four acetate, succinate, or nicotinate esters thereof; The oral care composition according to the present invention preferably contains one or more vitamins selected from the group consisting of TIFF2025529924000006.tif55128 or any of the four acetates, succinates, or nicotinates mentioned above, vitamin K, and any of the acetates, succinates, or nicotinates mentioned above, such as tocopheryl acetate (vitamin E acetate), wherein the total amount of the vitamins is preferably 0.0001% to 5% (w / w); the oral care composition according to the present invention preferably contains one or more vitamins. The vitamins may also include other vitamin-like compounds, such as choline, carnitine, or combinations thereof.

[0146] The oral care composition according to the present invention preferably comprises from 0.0001% (w / w) to 5% (w / w) of vitamins, such as from 0.01% (w / w) to 5% (w / w) or from 0.01% (w / w) to 2% (w / w) of vitamins.

[0147] In a preferred embodiment, the composition comprises one or more (e9) retinoid compounds. As used herein, "retinoid compounds" includes all natural and / or synthetic analogs of vitamin A or retinol-like compounds that retain the biological activity of vitamin A in the skin, geometric and stereoisomers of these compounds, and all natural and / or synthetic analogs of vitamin E. In one embodiment, (e9) comprises, and preferably consists of, one or more retinoid compounds selected from the group consisting of tretinoin; isotretinoin; alitretinoin; acitretin; etretinate; motretinide; adapalene (6-3-(1-adamantyl)-4-methoxyphenyl-2-naphthoic acid); arotinoids, acetylene retinoids; tazarotene (ethyl 6-2-(4,4-dimethylthiochroman-6-yl)-ethynylnicotinate), retinyl esters such as retinyl acetate, retinyl palmitate, retinyl propionate, and retinyl linoleate; retinal; retinoic acid; tocopheryl acetate; and tocopheryl retinoate. The retinoid compound may be contained as a substantially pure substance or may be contained in an extract obtained by appropriate physical and / or chemical isolation from a natural (e.g., plant) source. The compositions of the present invention can contain a safe and effective amount of a retinoid compound such that the oral care composition is safe and effective in regulating or improving the condition and incidental insults of keratinous tissue when applied to the oral cavity. Preferably, the total amount of the retinoid compound is 0.0001% (w / w) to 2% (w / w).

[0148] In a preferred embodiment, the composition preferably comprises jasmonic acid (JA), including jasmonates and their conjugates, gibberellins GA1 to GA136, including gibberellic acid and (GA1), ent-gibberellans, ent-kaurene (5,5,9-trimethyl-14-methylidenetetracyclo[11.2.1.0], ent-kaurene (5,5,9-trimethyl-14-methylidenetetracyclo[11.2.1.0]), ... 1,10 .0 4,9]-hexadecane), and zeatin (2-methyl-4-(7H-purin-6-ylamino)but-2-en-1-ol), preferably wherein the total amount of these compounds is 0.0001% to 1% (w / w). In a preferred embodiment, the composition comprises one or more JAs selected from the group consisting of methyl jasmonate (MeJA - jasmonic acid methyl ester), JA conjugated with isoleucine (Ile) (JA-Ile((+)-7-iso-jasmonoyl-L-isoleucine)), JA conjugated with an amino acid selected from the group consisting of arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, selenocysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, ptonith, phenylalanine, creatine, diaminobutonic acid, diaminopropionic acid, and alkali and alkaline earth salts of JA, preferably in a total amount of 0.0001% (w / w) to 2% (w / w);

[0149] In a preferred embodiment, the composition comprises one or more (e11) amino acids, including their salts and derivatives. In a preferred embodiment, the composition comprises one or more amino acids and derivatives thereof selected from the group consisting of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, diaminobutyric acid, and diaminopropionic acid; and creatine, including Na salts, K salts, and Li salts of any of the foregoing, and acetate forms of any of the foregoing, and preferably, the total amount of the one or more amino acids is 0.0001% (w / w) to 2% (w / w).

[0150] In a preferred embodiment, the composition comprises one or more (e12) oral-enhancing polyols (other than those in group (d)). Such polyols can be sugar alcohols, disaccharides, polysaccharides, and preferably non-reducing sugars. In a preferred embodiment, the composition comprises one or more polyols, more preferably dexpanthenol, selected from the group consisting of dexpanthenol (provitamin B5), cyclodextrins (e.g., 2-hydroxypropyl-β-cyclodextrin), mannitol, maltitol, lactitol, maltotritol, maltotetratol, polyglycitol, 1-O-α-D-glucopyranosyl-D-mannitol, 6-O-α-D-glucopyranosyl-D-glucitol, and isomalt, preferably dexpanthenol, wherein the total amount of the one or more polyols is 0.1% to 10% (w / w).

[0151] In a preferred embodiment, the composition comprises one or more (e13) hydroxy acids, including their salts and derivatives, preferably their sodium, potassium, and lithium salts. In a preferred embodiment, the composition comprises one or more hydroxy acids selected from the group consisting of acetic acid, propionic acid, salicylic acid, lactic acid, glycolic acid, acetylsalicylic acid, and other salicylic acid derivatives, preferably salsalate (a dimer of salicylic acid) and choline salicylate (a salt of choline and salicylic acid), more preferably salicylic acid, choline salicylate, and salsalate, preferably wherein the total amount of the preferred or more preferred hydroxy acids is 0.01% to 4%.

[0152] In a preferred embodiment, the composition comprises one or more (e14) fluoride components. In a preferred embodiment, the composition comprises one or more fluoride components selected from the group consisting of sodium monofluorophosphate, amine fluorides, and stannous fluoride, preferably wherein the total amount of the fluoride ions of the fluoride components is 0.0001% (w / w) to 0.5% (w / w), more preferably 0.0001% (w / w) to 0.2% (w / w), and even more preferably 0.0001% to 0.15% (w / w) (i.e., only the amount of fluoride is taken into account when assessing the amount of fluoride in the composition, and counterions are counted in group (e22)). However, the total amount of the fluoride components can be used (once) to assess the total amount of further components, preferably component (e), in the composition;

[0153] In a preferred embodiment, the composition comprises one or more (e15) sweeteners other than the polyol (d). In a preferred embodiment, the composition comprises at least one sweetener selected from the group consisting of saccharin (Na), dextrose, sucrose, lactose, levulose, aspartame, sodium cyclamate, D-tryptophan, dihydrochalcones, acesulfame, sucralose, and neotame, preferably wherein the total amount of sweeteners is 0.1% to 10% (w / w);

[0154] In a preferred embodiment, the composition includes one or more (e16) colorants. Those skilled in the art will understand that colorants can be already part of the vegetable oil or extract, or propolis, or can be added separately to the composition according to the present invention. The term colorant also encompasses orally acceptable anti-dyes, such as sodium hexametaphosphate. In a preferred embodiment, the colorant is selected from the group consisting of chlorophyll, indigo, beta-carotene, saffron, paprika, Green S, Patent Blue V, Quinoline Yellow, Carmoisine, Ponceau 4R, and sodium hexametaphosphate, and preferably, the total amount of colorant is 0.0001% to 1% (w / w).

[0155] In a preferred embodiment, the composition comprises one or more (e17) peptides. The three-letter code for amino acids is known to those skilled in the art. The term peptide encompasses fatty acid derivatives, peptide acetates, and Na, Li, and K salts of the peptides. In a preferred embodiment, the composition comprises one or more peptides selected from the group consisting of carnosine (beta-alanine and L-histidine; Ala-His), Gly-His-Lys, Arg-Lys-Arg, His-Gly-Gly; palmitoyl-Gly-His-Lys (commercially available, e.g., from Sederma, France), Arg-Lys-Arg, peptide E (Arg-Ser-Arg-Lys), Lys-Thr-Thr-Lys-Ser, palmitoyl-Lys-Thr-Thr-Lys-Ser (commercially available from Sederma, France), fatty acid derivatives, acetates, sodium salts, lithium salts, and potassium salts of any of the foregoing, preferably in an amount of 0.0001% to 2% (w / w) in total.

[0156] Sensations such as coolness, warmth, and tingling are useful for providing signals to the user.

[0157] In a preferred embodiment, the composition contains one or more cooling agents (e18). The most well-known coolant is menthol. Therefore, menthol, especially 1-menthol, can be added to the oral care composition according to the present invention. Among synthetic coolants, there are many derivatives structurally related to menthol, i.e., containing a cyclohexane moiety derivatized with functional groups such as carboxamide, ketal, ester, ether, and alcohol. Examples include p-menthane carboxamide compounds such as N-ethyl-p-menthane-3-carboxamide (commercially known as "WS-3"). An example of a synthetic carboxamide coolant structurally unrelated to menthol is N,2,3-trimethyl-2-isopropylbutanamide. Other exemplary synthetic cooling agents include 3-1-menthoxy-propane-1,2-diol, isopulegol, p-menthane-3,8-diol, alcohol derivatives such as menthone glycerol acetal (commercially known as "MGA"), menthyl esters (such as menthyl acetate, menthyl acetate, menthyl acetoacetate, and monomenthyl lactate), 3-methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one (3-MPC), 5- The cooling agents are alpha-ketoenamine derivatives including methyl-2-(1-pyrrolidinyl)-2-cyclopenten-1-one (5-MPC); 2,5-dimethyl-4-(1-pyrrolidinyl)-3(2H)-furanone (DMPF); and icilin (also known as AG-3-5, chemical name 142-hydroxyphenyl]-4-[2-nitrophenyl]-1,2,3,6-tetrahydropyrimidin-2-one), and preferably the total amount of these cooling agents is 0.0001% to 2% (w / w).

[0158] In a preferred embodiment, the composition comprises one or more (e19) warming agents, such as nicotinic acid esters (such as benzyl nicotinate), polyhydric alcohols, nonanoyl vanillylamide, nonanoic acid vanillyl ether, vanillyl alcohol alkyl ether derivatives (such as vanillyl ethyl ether, vanillyl butyl ether, vanillyl pentyl ether, and vanillyl hexyl ether), isovanillyl alcohol alkyl ethers, ethyl vanillyl alcohol alkyl ethers, veratryl alcohol derivatives, substituted benzyl alcohol derivatives, substituted benzyl alcohol alkyl ethers, vanillin propylene glycol acetal, ethyl vanillin propylene glycol acetal, ginger extract, ginger oil, gingerol, zingerone, or a combination thereof, and preferably, the total amount of these warming agents is 0.0001% (w / w) to 2% (w / w). For example, although ethanol and other short-chain (poly)hydroxy alcohols are also heating agents, they belong to the protic solvent (a) or, in the case of xylitol, erythritol, and sorbitol, to the polyol (d), and not to the further component (e). Moreover, those skilled in the art will understand that components with multiple effects (e.g., a polyhydric alcohol can be both a sweetener and a warming agent) are counted only once in group (e).

[0159] In a preferred embodiment, the composition comprises one or more (e20) tingling substances, such as capsaicin, homocapsaicin, jambu oleoresin, zanthoxylumpeperitum, sanshool-I, sanshool II, sanshoamide, piperine, piperidine, spilanthol, 4-(1-methoxymethyl)-2-phenyl-1,3-dioxolane, or a combination thereof, preferably in an amount of 0.0001% (w / w) to 2% (w / w) in total of these tingling substances.

[0160] In a preferred embodiment, the composition comprises one or more (e21) emulsifiers (compounds that help combine liquids of different concentrations). Emulsifiers usually have hydrophilic and hydrophobic residues. When they are added to immiscible liquids, the emulsifier molecules are located along the so-called interfacial layer, for example, where oil separates from water. Preferred, but non-limiting examples include sodium diphosphate (Na4P2O7), PEG300, PVPK90, lecithin, carrageenan, guar gum, xanthan gum, polysorbates (e.g., polyoxyethylene(20)-sorbitan-monolaurate (polysorbate 20), polyoxyethylene(20) sorbitan-monooleate (polysorbate 80), polyoxyethylene(20) sorbitan-monopalmitate (polysorbate 40), polyoxyethylene(20) sorbitan-monostearate (polysorbate 60), polyoxyethylene(20) sorbitan-monotristearate (polysorbate 65)), celluloses (e.g., cellulose, methylcellulose, ethylene glycol, propylene glycol, propylene glycol stearate ... Mono- and diglycerides of fatty acids (e.g., glyceryl monostearate, glyceryl distearate), sucrose esters and sucrose glycerides (E473 and E474), polyglycerol esters of fatty acids, polyglycerol polyricinoleate, stearoyl lauryl acrylate, cellulose, sodium carboxymethylcellulose, ethylhydroxyethylcellulose, sodium lauryl sulfate (SDS), cross-linked sodium carboxymethylcellulose (croscarmellose), enzymatically hydrolyzed carboxymethylcellulose (E469), mono- and diglycerides of fatty acids (e.g., glyceryl monostearate, glyceryl distearate), sucrose esters and sucrose glycerides (E473 and E474), polyglycerol esters of fatty acids, polyglycerol polyricinoleate, stearoyl lauryl acrylate lacylates) (e.g., sodium stearoyl-2-lactylate or calcium stearoyl-2-lactylate), sorbitan esters (e.g., sorbitan monostearate, sorbitan tristearate, sorbitan monolaurate, sorbitan monooleate, sorbitan monopalmitate). Preferably, the total amount of these emulsifiers is 0.0001% (w / w) to 5% (w / w).

[0161] The composition may contain further additives (e22) either as additives to commercial products used to provide components (a) to (e) or as metal ion sources, preferably NaCl, or Ca. 2+ , Mg 2+ , Zn 2+ , Fe 2+ / 3+ The metal ion source may be included either because of its beneficial effect or because it is added due to its beneficial effect, such as a source of metal ions. The metal ion source can be, for example, tea, cocoa, and lotus extracts, or the specific addition of a metal salt. Those skilled in the art will recognize which salts are sufficiently water soluble to provide metal ions to the gum / tooth surface, such as, for example, calcium acetate, calcium citrate, calcium lactate, CaCl2, CaNO3, FeCl2, FeCl3, Fe2(SO4)3, MgCl2, MgSO4, magnesium acetate, zinc acetate, zinc nitrate, ZnSO4, ZnCl, zinc chlorate (Zn(ClO3)2, and zinc perchlorate (CL2O2Zn), zinc gluconate, and zinc acetate. When the metal ion source is specifically added in the form of a salt, The amount of such salts is 0.001% (w / w) to 2.5% (w / w), more preferably 0.01% (w / w) to 1% (w / w). It should be noted that for the purpose of assessing the total amount of (e), the anions of such salts are also counted in group (e22). The term "further additives" encompasses all substances not mentioned in any of the main classes (a) to (d) and (e1) to (e22) but which may be present in the compositions according to the invention in an amount of 1% (w / w) or less, preferably 0.05% (w / w) or less (excluding the metal ion source).

[0162] Those skilled in the art will understand that although additional components in addition to components (a)-(d) may have additional beneficial effects on the composition, the successful results of the compositions according to the present invention are based on components (a)-(d) being present in their specific amounts, and in preferred embodiments, on (a)-(d) and (e4) being present in their specific amounts as described herein.

[0163] Oral care compositions In preferred embodiments, the "contact time" (the time during which at least 10% of the composition according to the invention is still on the mucosa, gums, or tooth surface, or inside a worn aligner splint) after application of the composition according to the invention is more than 2 minutes, preferably more than 10 minutes, preferably more than 30 minutes, more preferably 60 minutes or more, for example up to 3 hours, up to 6 hours, up to 8 hours, or more than 8 hours.

[0164] When using an aligner splint, the composition according to the present invention can be applied to the inside of the splint before inserting it (e.g., three doses, one to the anterior region of the splint and one to each side of the splint), so that when the splint is inserted, the composition according to the present invention is distributed and fixed between the splint and the gums or teeth via volume displacement. Alternatively, the composition according to the present invention can be applied to the relevant teeth and gums, or to the tissues and teeth around a dental implant, for example, immediately before inserting the aligner splint. The use of an aligner splint, or a splint designed to retain the formulation in the oral cavity for a longer period of time, such as a mouthguard, reduces salivation of the composition, thereby increasing the residence time of the composition and thus the exposure time. In such use of the composition according to the present invention, the exposure time is typically 60 minutes or more, preferably up to 3 hours, more preferably up to 6 hours, and even more preferably up to 8 hours, or even longer, depending on the length of time the aligner splint is worn. For the present invention, it is desirable to use a gel that can be easily applied, laid down in a thin layer, and distributed evenly over the gingival sulcus / pocket and long gingival gum line.

[0165] The oral care compositions of the present invention can be administered as (oral) sprays, gels (e.g., hydrogels), emulsions, dispersions, as part of dental strips, or chewing gums. Preferably, the oral care compositions of the present invention are hydrogels. Examples of oral care compositions include tooth / gingival gels, subgingival gels, dispersions, or emulsions for application to teeth, gums, and / or aligner splints. The compositions of the present invention can also be used to prepare mouthwashes, oral sprays, chewable tablets, chewing gums, dental strips, dental floss and dental floss coatings, dissolving breath-freshening strips, prosthetic care products, and dental care products, particularly aligner splint care products. Also described herein are methods of using the disclosed compositions to improve gum health in the oral cavity, preferably when wearing a splint, such as an aligner splint or mouthguard, or methods of using the compositions of the present invention to care for the gums when wearing a splint, preferably an aligner splint or mouthguard. The user can apply the composition to the teeth and / or gums and / or aligners themselves, or the composition can be applied by a third party, such as a dentist, orthodontist, or other medical or dental professional.

[0166] Preparation method The composition of the present invention can be prepared by simply mixing most of the components.Preferably, HA is first dispersed in ethanol (for example, 96%) or in a medium containing ethylene glycol, and then aqueous phase is added under stirring.Alternatively, HA can be added to a product containing ethanol or ethylene glycol, such as carbomer, before adding aqueous phase.

[0167] The additional components can be added to the aqueous phase before mixing the HA dispersion with the aqueous phase, or after combining the (suspended) HA with the aqueous phase, or some components can be added to the (ethanol / ethylene glycol) HA dispersion and other components can be added to the aqueous phase before mixing the HA with the aqueous phase, or after combining the (suspended) HA with the aqueous phase. Antioxidants such as catechins are preferably added to the compositions according to the present invention, preferably in the form of plant extracts, for example, tea extracts. Additional beneficial components such as vitamins, minerals, and other plant secondary substances can also be added directly as additional component (e) or in the form of extracts, for example, lotus extract components. Lotus extract is also preferably added to the compositions according to the present invention. Lotus extract is rich in armepavin, fatty acids, proteins, phosphorus acids, and linoleic acid, and has beneficial effects on the gum surface. In addition to fiber and vitamins, lotus extract contains important minerals such as compounds containing iron ions, copper ions, manganese ions, zinc ions, and K ions.

[0168] Furthermore, the pH of the composition is preferably 6 to 8. This can be achieved using any pharmaceutically acceptable buffering compound, or the sum of all components of the composition already provides the ambient pH value. In a preferred embodiment, the pH is adjusted with a buffer (system) selected from the group consisting of sodium bicarbonate, TRIS, and PBS. A pH below 6 accelerates tooth demineralization, while a pH above 8 is too far from the pH of the human oral cavity, which should be in the range of 6 to 7.5. If the pH value becomes too high, it may cause chemical burns in the oral cavity. The dispersion and mixing procedure can be preferably carried out at around 298 K, e.g., 298.15±25 K, although higher temperatures, such as up to 80°C, are also possible (as long as the components are not heat-sensitive). Preferably, the pressure is around 1.013 bar, e.g., 1.013±200 bar.

[0169] The method for preparing the composition according to the present invention comprises the following steps: - optionally calculating the amount of water-insoluble polymer to obtain the suitable viscosity disclosed herein; - dispersing HA in ethanol or ethylene glycol or in a solvent comprising ethanol or ethylene glycol; - adding an aqueous phase in which some or all of the other components are already dissolved, optionally adding the components after the aqueous phase (with or without some of the components) has already been combined with the dispersed HA, and stirring, preferably for at least 1 hour, until a hydrogel is formed; - optionally measuring the pH of the composition; - optionally adjusting the pH to a range of pH 6 to pH 7.5, preferably to a range of pH 7 (e.g. pH 7±0.3); - Optionally, measuring the viscosity (e.g. for quality control).

[0170] Those skilled in the art will understand that once the composition is properly formulated, the amount of water-insoluble polymer and protic solvent to obtain a suitable viscosity and / or viscosity measurement value is no longer required in the existing formulation; and pH measurement and pH adjustment may also no longer be required in the existing formulation.However, for quality control reasons, at least the step of measuring pH value, and if necessary, the step of adjusting pH value and / or the step of measuring viscosity should continue.

[0171] use The present invention also relates to a method for caring for the oral cavity, particularly the gums and / or teeth, comprising applying a composition according to the present invention to the oral tissues (e.g., oral mucosa, gums) or teeth of a user's oral cavity, preferably to the user's gums (or a portion of the gums), for an exposure time of at least 30 seconds, preferably more than 2 minutes, more preferably more than 10 minutes, and even more preferably more than 30 minutes, or even longer. When a splint, such as an aligner splint, mouth guard, or a splint designed to encircle (a portion of) the user's gums (i.e., one individually tailored to the user's dentures), is worn, the exposure time is typically 60 minutes or more, preferably up to 3 hours, more preferably up to 6 hours, and even more preferably up to 8 hours, or even longer, depending on the length of time the aligner splint has been worn. Pressing a composition according to the present invention between the gums, teeth, and (aligner) splint significantly slows / prevents the composition from spreading and its dilution by saliva. The application methods described herein involve contacting the oral care composition of the present invention with a person's oral mucosa (e.g., gum line or periodontal pocket). When a splint (such as an aligner splint) is worn, the gums and tooth areas inside the splint should preferably be brought into contact with the composition of the present invention. If an aligner splint is worn, the composition of the present invention can be applied to the inside of the aligner splint before insertion, so that when the aligner splint is inserted, it is secured between the splint and the gums or teeth via volume displacement. Alternatively, the composition of the present invention can be applied to the relevant teeth and gums immediately before insertion of the aligner splint. This also increases the residence time of the composition and therefore the exposure time. In such uses of the composition of the present invention, the exposure time is typically 60 minutes or more, preferably up to 3 hours, more preferably up to 6 hours, and even more preferably up to 8 hours, or even longer, depending on the length of time the aligner splint is worn."Immediately" before inserting an aligner splint preferably means at most 3 minutes, more preferably at most 1 minute, and even more preferably at most 30 seconds before inserting the aligner splint. The compositions according to the invention are preferably applied inside a splint, such as a mouthguard, a custom-fitted splint, or an aligner splint, or to the corresponding area of ​​the oral cavity, before each insertion of a splint, such as a mouthguard, a custom-fitted splint (i.e., a splint designed to increase the retention time of the composition but not to change the position of the teeth), or an aligner splint. Of course, other areas of the oral cavity can also be brought into contact with the compositions according to the invention.

[0172] The present invention further relates to a method of improving the health of a user's gums, comprising applying the oral care composition to the user's oral tissues, preferably along the gum line or sulcus.

[0173] One aspect of the present invention relates to the use of a composition according to the first aspect or any embodiment of the first aspect for treating gums and / or teeth covered by an aligner splint when the aligner splint is worn. Another aspect relates to a method for treating gums and teeth, comprising the steps of: a) applying a composition according to the first aspect or any embodiment thereof to the gums and teeth covered by the aligner splint when the aligner splint is worn; or applying a composition according to the first aspect or any embodiment thereof to the inside of the aligner splint, which surrounds a portion of the wearer's gums and teeth when the aligner splint is worn; b) placing the aligner splint in the oral cavity and wearing the aligner splint for at least 60 minutes. The composition according to the present invention can also be applied to skin (cutis) outside the mouth area.

[0174] Another aspect relates to a composition according to the first aspect or any embodiment thereof as a medicament.

[0175] A further aspect relates to a composition according to the first aspect or any embodiment thereof for use in treating inflammation, preferably of the skin, more preferably of the oral mucosa, even more preferably of the gums, preferably wherein the inflammation is periodontitis. This is also relevant for treating inflammation of tissues close to an implant.

[0176] Another aspect relates to a composition according to the first aspect or any embodiment thereof for use in treating stomatitis.

[0177] Another aspect relates to a composition according to the first aspect or any embodiment thereof for use in treating gum recession.

[0178] A further aspect relates to the use of a composition according to the first aspect or any embodiment thereof for preventing inflammation of the gums.

[0179] A further aspect relates to the use of a composition according to the invention for the treatment of dental or cervical sensitivity.

[0180] A further aspect relates to the fact that the use of the composition according to the invention can be used for the treatment of wounds of the skin, preferably of the oral mucosa, in particular of the gums, preferably small wounds (preferably cuts or abrasions in the oral mucosa that are 0.5 cm or less in size or whose longest extent is 0.5 cm or less).

[0181] Thus, the present invention also relates to a method for treating inflammation; or stomatitis; or gum recession; or dental or cervical sensitivity; or skin wounds, preferably of the oral mucosa, comprising applying a composition according to the first aspect or any embodiment thereof to the respective surface at least once within a 12 hour period, more preferably two, three, four or five or even more times within a 12 hour period.

[0182] In a preferred aspect, the composition according to the present invention is used in combination with a delivery vehicle such as a strip, a dental splint (including an aligner splint), or a sponge material for any of the uses or methods described above.

[0183] This application of the composition according to the present invention is preferably carried out at least once a day, preferably at least twice a day, and even more preferably at least three times a day for all uses and methods indicated herein.However, in general, the composition according to the present invention should not be used more than 15 times per day (i.e., within 24 hours), preferably not more than 10 times, and even more preferably not more than 6 times.

[0184] The compositions of the present invention can be applied using a syringe or disposable syringe, a squeeze tube, a brush, a penor or brush tip applicator, a cotton swab, a lip gloss applicator, a toothbrush, a strip that is removed after use, or even using the fingers.

[0185] After the desired time has elapsed, any residue can be simply removed by wiping, brushing, or rinsing the surface. Alternatively, the remaining composition can be left in contact with the surface of the mouth. The composition according to the present invention will disappear from the teeth / oral mucosa, particularly the gingival surface, over time due to diffusion, movement within the mouth, and / or saliva secretion.

[0186] A further aspect of the present invention relates to a kit comprising a container containing a composition according to the present invention, which is suitable for applying the composition to the appropriate area of ​​the oral cavity or splint, and instructions on how to use the composition according to the present invention. [Example]

[0187] Commercially available components were used to prepare the compositions. The following examples demonstrate the composition and use of the compositions of the present invention, but are not intended to limit the inventive concepts thereto. (a) - Water (CG, PRO, CE(I)), tap water - Glycerol (99.7%) (Labordiscounter, the Netherlands) - Ethanol (EtOH) (supplied by CG, PRO, CE1 (see below), and Roth, Karlsruhe, Germany) - Propylene glycol (propane-1,2-diol) (CG, see below) - Pentylene glycol (Merck, Karlsruhe, Germany) (b) - Carbomer Gel pH 6.5 NRF S43 (Carbomer 35,000 1g, trometamol (tris(hydroxymethyl)aminomethane (TRIS)) 1g, edetate sodium (ethylenediaminetetraacetic acid sodium (EDTA)) 0.1g, propylene glycol 10g, water 100g) manufactured by Caesar & Lorent GmbH, Hilden, Germany (CG) - D-galacto-D-mannan (CAS 11078-30-1) (mannose / galactose ratio 3.4:1) derived from carob, low-substituted hydroxypropyl cellulose (CAS 9004-64-2), carboxymethyl cellulose sodium salt (CAS 9004-32-4) from Merck SigmaAldrich, Darmstadt, Germany - D-galacto-D-mannan (CAS 39300-88-4) from Caesalpinia spinosa (mannose / galactose ratio 3:1) manufactured by Dragonspice Naturwaren, Reutlingen, Germany - Sodium hyaluronate (HA I) 8000-12000 Da (HA I) manufactured by Laboratories Hyamed SA, Geneva, Switzerland - Sodium hyaluronate 10,000-50,000 Da (HA II) from Alexmo cosmetics GmbH, Stuhr, Germany - Sodium hyaluronate 1200-1800kDa (HA III) from ExperChem Limited Weinheim, Germany (c) - Chamomile extract (1:4, 40% ethanol - extract contains 1.44% alpha-bisabolol and 0.9% chamazulene) from Viatris, Steinhausen, Switzerland (CE I) - Chamomile extract (CO2 extracted - alpha-bisabolol content 1.4% and matrycin content 0.51%) (CE II) from Flavex Naturextracts GmbH, Rehlingen-Siersburg, Germany - Alpha-bisabolol, eugenol, curcumin, beta-caryophyllene ((-)-trans-caryophyllene, trans-(1R,9S)-8-methylene-4,11,11-trimethylbicyclo[7.2.0]undec-4-ene, empirical formula (Hill notation)) (CAS 87-44-5), chlorhexidine (CAS 66-56-1), hexadecylpyridinium chloride monohydrate (CAS 6004-24-6) from Merck SigmaAldrich, Darmstadt, Germany - Matricin manufactured by BioCrick, Chengdu, China - Eugenol (Speiko, Munster, Germany) (d) Xylitol, erythritol, and sorbitol from Merck SigmaAldrich, Darmstadt, Germany (e) - Propolis extract (PRO) from Hoyer GmbH, Polling, Germany, 1.2% propolis in 40% ethanol - 90% catechins from freeze-dried green tea extract (EC:ECG:EGC:EGCG distribution 5:9:14:31) (catechins) from NatuGena GmbH, Ingolstadt, Germany - EGCG hydrate (CAS 989-51-5) HPLC purity >98.0% and EC (CAS 490-46-0) HPLC purity >97.0% from TCI Zwijndrecht, Belgium - Mentha americana leaf oil, menthol content 63% (Essence-pur GmbH Lohmar, Germany) - Allantoin, 2-phospho-L-ascorbic acid trisodium salt (sodium ascorbyl phosphate), beta-carotene, stannous fluoride (SnF2), retinol, menthol, methylparaben, sucrose monolaurate, sodium lauryl sulfate (SDS) (Merck Reutlingen, Germany) - Dexpanthenol Provitamin B5 (Labordiscounter, the Netherlands) - NaOH (Labordiscounter, the Netherlands) was used to prepare a 50% NaOH solution. - PBS buffer pH 7.4 - 10x concentrate (Morphisto GmbH Offenbach, Germany) diluted 1:9 (1x PBS containing 8.184g NaCl, 1.8g Na2HPO4, and 0.3g KH2PO4) - Saccharin sodium (Freyalab Hadzhidimovo, Bulgaria) - Polyethylene glycol PEG300, polyvinylpyrrolidone PVP K90, sodium diphosphate (Na4P2O7) and sodium bicarbonate (NaHCO3), tocopheryl acetate (vitamin e acetate) (Roth, Karlsruhe, Germany) - Ethyl-p-menthane-3-carboxamide (TCI Chemical, Eschborn, Germany) - Chlorhexamed 1% gel (GlaxoSmithKline GmbH, Munchen, Germany) (chlorhexidine 1.13 mg / 0.2 g gel = 0.565% (w / w); further ingredients: 2-propanol, hyprolose, sodium acetate, macrogol glycerol hydroxystearate, water).

[0188] Compositions containing CG were prepared by combining CG with additional EtOH-containing components (e.g., PRO and CE I) and adding HA in portions under stirring at room temperature for 2 hours until a homogeneous dispersion was formed. Water was added in portions (dropwise) under stirring, and then additional components were added under stirring.

[0189] For compositions containing D-galacto-D-mannan, hydroxypropyl cellulose, or sodium carboxymethylcellulose, HA was first dispersed in 96% by volume of EtOH under stirring. Additional components, including EtOH, were then added dropwise, followed by the addition of D-galacto-D-mannan, hydroxypropyl cellulose, or sodium carboxymethylcellulose in small portions. After stirring at room temperature for 2 hours, water and additional components were added dropwise / as solids under stirring. Solids (water-soluble) were either first dissolved in water, and then the respective amounts of solution were added to the composition (for calculations, the amount of water was added to the amount of water in item (a) in the table below), or the solids were added to the combined HA and water phases, and the resulting composition was stirred until all solids were dissolved.

[0190] TIFF2025529924000007.tif199142TIFF2025529924000008.tif241142TIFF2025529924000009.tif247142TIFF202 5529924000010.tif247142TIFF2025529924000011.tif248142TIFF2025529924000012.tif247146TIFF2025529924 000013.tif246142TIFF2025529924000014.tif247154TIFF2025529924000015.tif247142TIFF2025529924000016. tif246142TIFF2025529924000017.tif246142TIFF2025529924000018.tif246142TIFF2025529924000019.tif41142

[0191] Example 14: Improving the oral sensation of aligner splint support First, the users were informed about the area to be applied. During the study, they were instructed on how to perform oral hygiene (brushing their teeth for 2 minutes twice a day, in the morning and in the evening). To ensure equal conditions, this oral hygiene started one week before the start of the experiment. All participants had the same prerequisites before the start of oral hygiene. During the test, one application of 0.5 ml each was placed on the left, right, and center of the inside of the aligner splint in the morning, midday, and evening after meals, and the aligner splint was (re)introduced into the mouth.

[0192] Half of the users were female and half were male, and all users were between 30 and 60 years old. Samples were randomly assigned, but care was taken to ensure that 5 male and 5 female users received each sample. The initial assessment included a questionnaire that asked about the interaction between taste in the mouth, halitosis, and dry mouth. These factors were asked using a journal-style quality of life questionnaire. Users were asked to rate their own taste in the mouth, halitosis, and dry mouth on a scale of 1 to 5. To avoid misunderstandings, it was explicitly pointed out in advance that for taste in the mouth, 1 was defined as pleasant (most positive) and 5 was defined as unpleasant (most negative); for bad breath, 1 was defined as not detecting bad breath (most positive) and 5 was defined as detecting strong bad breath (most negative) (bad breath should be determined by exhaling into one's hand and immediately breathing through the nose); and for dry mouth, 1 was defined as not detecting dryness (most positive) and 5 was defined as extremely dry mouth (most negative).

[0193] All aligner splint users had unremarkable mouth appearance before aligner treatment. All test results were collected weekly for six weeks, on the first day of each week and at the end of week six. The aligner splints were worn overnight for the nine-hour questionnaire. The one-hour questionnaire was administered after lunch and one hour after the aligners were put back on.

[0194] Ten different aligner splint users were given each sample. The experiment was performed as a double-blind experiment. Neither the users nor the dentists knew which sample number was assigned to which sample. Samples 1-3 corresponded to the commercial product, Sample 4 was a placebo (water), and Samples 5-11 corresponded to Examples 1-7.

[0195] The average value was calculated from seven completed questionnaires per user. Non-whole numbers and those with a tenth-place digit of 0, 1, 2, 3, or 4 were rounded down. Remaining tenth-place digits of 5, 6, 7, 8, or 9 were rounded up. Thus, each value is based on the average of 70 individual values ​​(10 users per sample, seven questionnaires per user). In 12 cases, a missing entry occurred on a single day in the corresponding questionnaire. In these cases, the evaluation was calculated using 69 individual values ​​instead of 70 (see Table 1). There were no duplicates in the forgotten entries; that is, there were either 69 or 70 individual values ​​for all questions. All testing with users was conducted under confidentiality agreements.

[0196] (Table 1) Questionnaire results TIFF2025529924000020.tif255162

[0197] Example 15: Reduction of Bleeding on Probing (BOP) BOP is a diagnostic technique for assessing inflammation of the gums or periodontal tissues. The dentist used a blunt periodontal probe (WHO probe) to probe the bottom of the gingival sulcus with light pressure at six measurement points per tooth (the examined tooth was, of course, part of aligner splint treatment). Bleeding sites were recorded, and the percentage of bleeding was calculated after a complete examination. The fewer the number of bleedings, the more stable the gums. A value of 25% was applied as the threshold. During the test period, all users were required to brush their teeth twice a day, after breakfast and dinner. During the test, one application of 0.5 ml each was placed on the left, right, and center of the inner side of the aligner splint, and the aligner splint was (re)introduced into the mouth after morning, midday, and evening meals. Control I (placebo) was water. All applications were performed with a 1 ml syringe. Unless otherwise stated, results are based on groups of 10 individuals (see DE10 2022 003 105.1, filing date August 26, 2023). In Examples 1 and 7, 5 additional individuals were treated in addition to the original 10 individuals (Example 1 results for the original 10 individuals were 2 / 10 on day 1, 3 / 10 after 6 weeks, and 2 / 10 after 12 weeks; Example 7 results for the original 10 individuals were 1 / 10 on day 1, 1 / 10 after 6 weeks, and 2 / 10 after 12 weeks (see DE10 2022 003 105.1)).

[0198] Example 13 and Control II were administered to five individuals per group. The individuals in this group were not aligner splint users but had experienced bleeding gum problems for at least two months prior to the study period. Individuals applied 1.5 ml of Example 13 via a toothbrush in the morning and evening after regular tooth brushing. Control Placebo II was administered as 1.5 ml of 0.001% menthol in 1.5% hydroxypropyl cellulose hydrogel (1.5 ml per application after morning and evening tooth brushing).

[0199] The data in Table 2 represent the number of users with a BOP index above 25%. All testing was performed as double-blind studies, i.e., a third party labeled the opaque sample bottles, and neither the individuals nor the dentists knew which sample number referred to mouthwater, mouth cream, control, or experimental example (all testing with individuals was conducted under confidentiality agreements).

[0200] (Table 2) Results of the BOP test TIFF2025529924000021.tif110159 1 Based on 15 individuals. 2 Based on five individuals who did not use aligner splints but had a generally high BOP.

[0201] Notably, the placebo group and the mouthwater group complained of application problems. In addition, the groups tested with the placebo, mouthwash, and mouth cream, as well as Example 3 and Example 6 (both not according to the present invention), showed a significant deterioration in gum condition during the test phase. Users of the placebo, mouthwash, mouth cream, and Example 6 stated that the initial strong taste of the application quickly disappeared, indicating that the application did not adhere to the gum and tooth surfaces for long enough. The reduced amount of xylitol in Example 3 may not inhibit plaque formation sufficiently strongly. These adverse effects were less severe in the oral gel user group (Kamistad), but still existed, indicating that the gel exhibits some kind of longer-lasting effect.

[0202] In contrast, Examples 1, 1a, 2, 4, 5, 7, and 7a showed very good results even after 12 weeks. Moreover, comparing Examples 1 and 1a, and Examples 7 and 7a, respectively, the presence of antioxidants (tea-derived catechins in Samples 1a and 7a) results in better gum protection or even gum regeneration.

[0203] Example 16: Gum recession caused by wearing aligners Dentists regularly examine the health of the gums, thereby monitoring the height of the gums in the interdental spaces. The gums of aligner splint users recede due to stress during aligner splint wear. Figure 1 shows an example of a set of teeth with healthy gums before the start of aligner treatment (1A), an example of the same set of teeth 12 months after the start of aligner splint treatment with gum recession and inflammation (arrows) (1B), and an example of the same set of teeth 7 days after application of Example 2 of the present invention (and 7 days after measurement of Image 1B). Figure 1 can also be provided as a color photograph. Due to the long time frame and difficulty in comparability, we have shifted our focus to other experiments demonstrating the superior effects of the composition of the present invention over the prior art.

[0204] Example 17: Hypersensitivity Sensitivity was tested using a thermal stimulus. This involved blowing air from a dental air blower onto the teeth. Room temperature was 21°C. Tooth temperature averaged 33°C. The cooler air removes heat from the tooth surface due to the temperature difference. The airflow stimulus was applied to the teeth at a temperature of 21°C and a pressure of 4.14 bar, at a distance of 1 cm, for a duration of 1 second.

[0205] The assessment was performed using the Schiff Cold Air Sensitivity Scale (SCA) and noted by the dentist: 0: Subject does not respond to airflow stimulation; 1: Subject responds to airflow stimulation but does not request removal of the stimulus; 2: Subject responds to airflow stimulation and requests removal of the stimulus or withdraws from the stimulus; 3: Subject responds to the airflow stimulus, perceives it as painful, and requests removal of the stimulus.

[0206] Initial results show that five individuals (1-5) with hypersensitivity began to decrease their sensitivity after seven days with three treatments (1.5 ml of the composition according to Example 29). Additional individuals with hypersensitivity were treated with compositions according to Examples 6 (not according to the invention), 7, 7a, 11, and 12, respectively, and placebo (0.001% menthol (gel) in 1.5% hydroxypropyl cellulose hydrogel (C1 and C2)) (see Table 3). In the morning, midday, and evening, 1.5 ml of each composition was applied to the teeth and gums by gently rubbing with a toothbrush for one minute per application. All tests were conducted as double-blind tests, i.e., a third party labeled the opaque sample bottles, and neither the individuals nor the dentists knew which sample numbers referred to which samples (all tests with individuals were conducted under confidentiality agreements):

[0207] (Table 3) Results of the SCA test TIFF2025529924000022.tif160147

[0208] The control groups C1 and C2, as well as the individuals using the composition of Example 6, did not show any significant change in hypersensitivity. In contrast, the composition according to the present invention showed a significant reduction in hypersensitivity already after 7 days, with very good results after 21 days of daily treatment. The presence of antioxidants (see Examples 7a, 11, and 12 (containing antioxidants) vs. Examples 2 and 7) appears to accelerate this beneficial effect.

[0209] Example 18: Viscosity determination The kinematic viscosity was determined using a Bohlin Instruments rotational rheometer (Gemini-Advanced Rheometer). A 4° / 40 mm diameter cone-plate with a standard smooth surface (stainless steel) (Order No. 3628 / J01 / 41, Bohlin Instruments, Pfortsheim, Germany) served as the measurement geometry. All measurements were performed in triplicate. The results of Examples 2, 4, and 5 were confirmed by measurements of Examples 2, 4, and 5 using a Kinexus Prime pro+ Rheometer (Order No. KNX2036, NETZSCH-Geraetebau GmbH, Selm, Germany) with a standard smooth surface (stainless steel) of 4° / 40 mm.

[0210] Measurements for Example 2 are illustratively listed in Table 4 (generated using a Gemini - Advanced Rheometer). Further measurements are summarized in Table 5.

[0211] Table 4: Viscosity measurement results using a rheometer in Example 2 TIFF2025529924000023.tif118152TIFF2025529924000024.tif221152

[0212] (Table 5) Viscosity data by rheometer TIFF2025529924000025.tif65128

[0213] The viscosity value at a shear rate of 1 [1 / s] and the extrapolated flow point at a shear rate of 0 [1 / s] were used as characterization values. For illustrative purposes, Figure 2 shows shear stress versus shear rate, and Figure 3 shows viscosity versus shear rate for Examples 1, 2, and 6 (not according to the present invention). In Example 2, the gel structure was properly established, leading to good applicability through shear thinning. The viscosity at a shear rate of 1 [1 / s] for the composition of Example 3 (not according to the present invention), but with a polymer composition similar to that of Example 2, also exhibited good behavior. Examples 4, 5, 7, 9, 9a, 10, and 11 also exhibited good viscosity behavior. The yield point of the composition from Example 1 was 1-4 Pa. The average viscosity at a shear rate of 1 [1 / s] was 23±6 [Pas]. Due to the low pH of the sample, incomplete gelation of the carbomer may have occurred. Example 8c exhibited similar behavior. An amount of 0.42% (w / w) of HA already reached sufficient gel formation to avoid Newtonian behavior of the samples. In contrast, samples from Examples 6 and 8c exhibited more Newtonian behavior, and the samples did not exhibit sustained gel formation.

[0214] Example 19: Scanning Electron Microscopy (SEM) Analysis Sample preparation Test specimens of (1) clear aligner (CA) material (polyethylene terephthalate-glycol copolyester) from Scheu Dental GmbH, Iserlohn, Germany, (2) titanium (Ti), and (3) polymethyl methacrylate (PMMA) were formed as small circular plates (2.5 mm in diameter) with flat, polished surfaces. An aligner splint was prepared with 2 × 3 compartments for the test specimens, and the compartments were attached to the inner surface of the aligner so that the test specimens were trapped between the teeth / gums and the aligner splint when the aligner splint was introduced into the mouth (Figures 4A and 4B).

[0215] Prior to sample preparation, all specimens and aligner splints were plasma sterilized (using a Plasma Mini from Plasmapp, Daegu, Seoul, Korea, according to the manufacturer's instructions) to ensure comparable baseline conditions. Biofilm formation was determined on the surface of the specimen (which is closest to the gums / teeth when the aligner splint is placed in the mouth). The first application of the sample was performed at the beginning of the wearing period (t = 0 hours), and the second application was performed 11 hours into the wearing period (t = 11 hours). The aligner splints were removed only for meals (mouth rinsing was performed after meals, but the aligners were not rinsed, as this could interfere with the attached specimens). Measurements were performed in triplicate at random locations on the surface at time 0 and 22 hours after wearing the aligner splint.

[0216] Figures 4C-4E show biofilm formation on the surface of CA at time 0 (4C); at 22 hours without treatment (4D); and at 22 hours with two treatments with Example 2 (4E). Figures 4F-4H show biofilm formation on the surface of Ti at time 0 (4F); at 22 hours without treatment (4G); and at 22 hours with two treatments with Example 2 (4H). The black areas on the surfaces at time 0 and 22 hours were identified as pits still present on the polished titanium surface. The differentiation of biofilm formation (see (4G)) and pitting was shown by EDS mapping. Figure 5 shows EDS mapping of a map cutout, here exemplarily the differentiation of Ti and biofilm in (4G) (resolution 64 x 64 pixels, FOV: 269 μm, mode: 10 kV-point, detector: BSD Full. The EDS mapping of (4F) showed no biofilm formation, and the EDS mapping of (4H) showed only a small amount of biofilm formation (less than 5%, which also correlates with the findings in Example 20). The PMMA specimens confirm the findings with CA and Ti, although the nature of the PMMA material used and the resulting uneven surface were not optimal for these measurements.

[0217] Example 20: Epifluorescence microscopy For epifluorescence microscopy, Ti specimens were used because of the resulting black background of the specimens. The same trend was observed with specimens made of CA, PMMA, and a multifunctional acrylate / methacrylate composite (10:1) (Merz Dental GmbH, Lutjenburg, Germany), frequently used by dentists. However, the best contrast for evaluating the fluorescence of stained biofilm formation was obtained with Ti because these materials produce a green background due to their inherent fluorescence.

[0218] "In vivo" For the preparation of in vivo samples, Ti specimens were prepared and incubated as described under Example 19, except that only one specimen per side of the splint was used (the other two of the three compartments per side remained empty). Meals and meal times during the incubation period for all samples were recorded. On both sides of the splint, 0.5 ml of each sample was added inside the splint near the compartment where the specimen was placed. Unlike in Example 19, biofilm formation was determined after 24 hours (instead of 22 hours). After 24 hours, the specimens were carefully removed from the splint and frozen at -80°C until measurement.

[0219] "In vitro" The same Ti specimens were prepared as described in Example 19. Saliva samples from five individuals were combined. The Ti specimens were added to a sealed 1.5 ml microreaction vessel (Eppendorf, Hamburg, Germany) along with 0.5 ml of combined saliva and 0.2 g of sample. The vessel was vortexed for 10 seconds and then incubated at 37°C for 24 hours using a Melag 80 incubator (Melag, Medizintechnik oHG, Berlin, Germany). Unlike Example 19, biofilm formation was determined after 24 hours (instead of 22 hours). After 24 hours, the specimens were carefully removed from the splint and frozen at -80°C until measurement. For measurement, the specimens were stained for 20 minutes in 1 ml of a 0.02% solution of acridine orange (CAS 26-94-6, Merck, Darmstadt, Germany) in sterile deionized water. The specimens were washed twice in sterile distilled water and air-dried at room temperature. All procedures were performed under protection from sunlight. Stained specimens were examined under a Zeiss Axioplan microscope (Zeiss, Oberkochen, Germany) equipped with a 50W mercury-hydraulic high-pressure bulb, a 20x objective (Zeiss, Plan-Neofluar), and Zeiss filter set No. 09 (excitation: 450-490 nm; dichroic beam splitter ≥ 510 nm; emission ≥ 520 nm, Zeiss, Oberkochen, Germany). Analysis of digitized images was performed using a low-light video camera and an image analyzer (both from Intas Science Imaging Instrument GmbH, Göttingen, Germany). Digitized image data was transferred to a computer, and the pixel size of stained microbial cells in the biofilm was determined using ImageJ 1.54d (Wayne Rasband and contributors, National Institutes of Health, USA) with the following settings: Distance in pixels 1018, Known distance 100 μm (determined with a straight line marking tool) Pixel aspect ratio = 1 Unit of length = μm global Picture Type 8-bit Adjust the threshold with "Strg+Shift+T" (same threshold for similar biofilm formation) Analyze particles with size 0 to infinity and circularity 0 to 1

[0220] In vivo results Figure 6 shows the results of fluorescence measurements of 10 random fluorescence photographs. The biofilm coverage of the Ti surface (y-scale in Figure 6) was determined as described above. The control showed extensive coverage (70.1 ± 15.83%) and strong fluorescence (see, e.g., Figure 7D). Commercially available chlorhexidine gel also showed extensive coverage (56.22 ± 12.23%), but the fluorescence intensity was lower (see, e.g., Figure 7A). Example 9b (see also Figure 7B), which is similar to Example 10 (not according to the invention) of KR1020000031162, each performed very well (only 1.51 ± 1.25%, respectively). 3.36±1.58%; and 4.07±1.66% coverage) showed high fluorescence (indicative of biofilm formation) compared to Examples 11a, 11, and 11b (see Figures 7F, 7E, and 7C, respectively; essentially no fluorescence / no biofilm formation). Although the amount of chlorhexidine in Example 11a is significantly less (0.01% (w / w)) compared to the amount of active ingredient in commercially available CHX gel (0.565% (w / w)), the inhibitory effect of the sample was significantly less than that of the CHX gel. Moreover, it was surprisingly found that the effect of the composition containing alpha-bisabolol (Example 11) appears to have a slightly better or similarly good inhibitory effect compared to the composition containing hexadecylpyridinium chloride (Example 11b). Moreover, Example 11 shows the superior effect of the formulation according to the present invention compared to compositions known in the art (e.g., Example 9b). For comparison, the amount of triclosan in Example 10 (KR1020000031162 In Example 11, alpha-bisabolol (0.1% (w / w)) was replaced by the same amount of alpha-bisabolol in Example 9b of the present application. Although the amount of alpha-bisabolol and matricin in Example 11 is ten times lower (0.01% (w / w)), Example 9b is significantly less effective in inhibiting biofilm formation (12.39±2.77% biofilm coverage in the presence of Example 9b vs. 3.36±1.58% biofilm coverage in the presence of Example 11 according to the present invention).

[0221] It should be noted that the results of in vivo and in vitro tests cannot be compared with each other due to different experimental settings: on the one hand, the constant salivation (albeit reduced by the splint) and the presence of the gums and tooth surface allow different growth conditions and the introduction of new bacteria or nutrients to the latter, and the (reduced) salivation removes the sample, while on the other hand, the sample volume and medium volume are constant in a sterile environment (reaction vessel).

[0222] In vitro – Results The in vitro control (water) showed a surface coverage of 35.11±4.75% on the Ti specimens after 24 hours. Example 8c (not according to the invention) demonstrates a significantly reduced biological anti-inflammatory effect and a significantly reduced mucoadhesive effect (resulting in a surface coverage by biofilm in the range of 26.51±4.09%) due to the reduced amount of HA in the formulation (0.1% (w / w)) compared to the composition of Example 8 according to the invention, in which the amount of HA was 1.44% (w / w) (3.14±0.73%) (the amount of alpha-bisabolol was the same in both formulations). In experiments using Example 8a, in which the amount of alpha-bisabolol was six times higher than in Example 8, the surface biofilm coverage was only 1.86±0.72%. Also, Example 8b (according to the present invention, containing 0.42% (w / w) HA and 0.01% (w / w) alpha-bisabolol) showed much better results than Example 8c, and better results than Examples 8 and 8a (each containing 1.44% (w / w) HA). Example 6 (not according to the present invention, containing 0.3% (w / w) HA) did not perform as well as Examples 8-8b (biofilm coverage 8.33±0.87%). In contrast, Examples 7-7c, each containing two water-insoluble polymers, showed very good results in terms of inhibiting biofilm formation (0.64±0.2%, 0.47±0.26%, 1.21±0.18, and 0.47±0.05). On the other hand, Example 9 (not according to the present invention, but similar to Example 1 of US2020 / 0390676) showed a biofilm coverage of 9.15±1.81%, i.e., low inhibition of biofilm formation. Indeed, US2020 / 0390676 does not teach the use of additional anti-inflammatory compounds in combination with specific amounts of xylitol, erythritol, or sorbitol, except that only eugenol was mentioned as a flavoring. Without being bound by any explanation, it is at least the low amount of xylitol (not according to the present invention) that results in the limited inhibitory activity of the formulation compared to the formulation of the present invention.Examples 10 to 13a (according to the present invention) also showed good to excellent inhibitory effects (4.69±0.88%, 1.75±0.54%, 5.67±2.97%, 0.44±0.22%, 0.76±0.27%, 3.67±1.55%, 3.61±1.14%, see also Figure 8).

Claims

1. (a) at least one protic solvent, wherein the at least one protic solvent is water, and wherein the total amount of all protic solvents is between 45% (w / w) and 85% (w / w), and the amount of water is at least 45% (w / w); (b) at least one water-insoluble polymer, wherein the at least one water-insoluble polymer is hyaluronic acid (HA), and wherein the total amount of all water-insoluble polymers is 0.4% (w / w) to 5% (w / w); (c) one or more sugar alcohols (polyols) selected from the group consisting of sorbitol, xylitol, and erythritol, wherein the total amount of polyols selected from the group consisting of sorbitol, xylitol, erythritol, and combinations of two or three of said three polyols is 10% (w / w) to 50% (w / w); (d) at least one other anti-inflammatory component selected from the group consisting of alpha-bisabolol, chamazulene, matricin, curcumin, beta-caryophyllene, eugenol, camphor, cineole, cuminaldehyde, thujone, chlorhexidine, povidone-iodine, cetylpyridinium chloride or bromide, and ursolic acid, wherein the total amount of all other anti-inflammatory components (d) is 0.001% (w / w) to 2% (w / w). wherein the total of (a), (b), (c), and (d) is 90% (w / w) to 100% (w / w); Oral care compositions.

2. L-ascorbic acid or its derivatives, dibutylhydroxytoluene, butylhydroxyanisole, superoxide dismutase, carotenoids, astaxanthin, rutin or its derivatives, hesperidin, quercetin, catechin; gallic acid or its derivatives, allantoin (N-(2,5-dioxoimidazolidin-4-yl)urea) and its derivatives, glutathione or its derivatives, glutathione, β-carotene or its derivatives, ubiquinol, polyphenols, hydrangea, turmeric, star anise, echinacea, scutellaria root, Hypericum erectum, Chinese gall nut, Geranium thunbergii, rice, rice bran, comfrey, Japanese pepper, Xanthoxylum 10. The composition of claim 1, comprising one or more antioxidants selected from the group consisting of (a), (b), (c), (d), (e), (f), (g), (h), (i), (j ...

3. The composition of claim 1 comprises the groups (a), (b), (c), and (d) as defined in claim 1 and one or more further components (e), wherein the total amount of all further components (e) is 10% (w / w) or less, preferably wherein the further components (e) are selected from the group consisting of (e1) (extracts and oils), (e2) buffers, (e3) chelating agents, (e4) antioxidants, (e5) preservatives, (e6) humectants, (e7) flavorings, (e8) vitamins, (e9) retinoids, (e11) amino acids, (e12) mouth-enhancing polyols, (e13) hydroxy acids, (e14) fluorides, (e15) sweeteners, (e16) colorants, (e17) peptides, (e18) cooling agents, (e19) warming agents, (e20) tingling agents, (e21) and (e22).

3. The composition of claim 1, wherein the total of (a), (b), (c), (d), and (e) is selected from the group consisting of (a), (b), (c), (d), and (e), and (e) must always add up to 100%.

4. The composition of any one of the preceding claims, wherein (b) comprises HA and one additional water-insoluble polymer, and wherein the total amount of all water-insoluble polymers is 0.9% (w / w) to 5% (w / w), and wherein the amount of hyaluronic acid is at least 0.8% (w / w).

5. 10. The composition of claim 1, wherein (b) comprises HA and at least one additional water-insoluble polymer selected from the group consisting of carbomer, mannan, and cellulose.

6. The composition according to any one of the preceding claims, wherein the HA or its sodium salt has a molar mass of between 5 kDa and 2000 kDa.

7. 10. The composition of claim 1, wherein (c) consists of one or more polyols selected from the group consisting of xylitol and erythritol.

8. 10. The composition of claim 1, wherein (d) comprises one or more compounds selected from the group consisting of alpha-bisabolol, chamazulene, matricin, eugenol, curcumin, beta-caryophyllene, chlorhexidine, povidone-iodine, cetylpyridinium chloride, and cetylpyridinium bromide.

9. 10. The composition according to claim 1, wherein the viscosity of the composition at a shear rate of 1 [1 / s] and a temperature of 22°C is from 10 Pas to 800 Pas.

10. 10. The composition of any one of the preceding claims, wherein the pH of the total composition is between pH 6 and pH 8, more preferably between 6.8 and 7.

8.

11. 10. The composition of any preceding claim, which is free of triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol).

12. The amount of each component selected from the group consisting of calcium pyrophosphate, calcium hydroxyapatite, diatomaceous earth, wollastonite, perlite, PMMA, and silicon beads, if present, is 0.00001% (w / w) or less; the amount of dicalcium phosphate, if present, is 0.008% (w / w) or less; the amount of each component selected from the group consisting of tricalcium phosphate, calcium metaphosphate, and calcium polyphosphate, is 0.0016% (w / w) or less; and the amount of calcium carbonate is 0.001% (w / w).

10. The composition of claim 9, wherein the amount of strontium carbonate in the composition is 0.0008% (w / w) or less; the amount of sodium bicarbonate is 7.4% (w / w) or less, preferably 1% (w / w) or less; the amount of fused silica is 0.0008% (w / w) or less; the amount of each component selected from the group consisting of fumed silica, precipitated silica, hydrous silica, and silicon beads is 0.0009% (w / w) or less; and the amount of barium sulfate is 0.0017% (w / w) or less.

13. 10. The composition of any one of the preceding claims, which is free of calcium pyrophosphate, calcium hydroxyapatite, diatomaceous earth, wollastonite, perlite, PMMA, silicone beads, dicalcium phosphate, tricalcium phosphate, calcium metaphosphate, calcium polyphosphate, calcium carbonate, strontium carbonate, fused silica, fumed silica, precipitated silica, hydrous silica, silicone beads, and barium sulfate.

14. 10. Use of a composition according to any one of the preceding claims for treating tooth or cervical sensitivity.

15. Use of a composition according to any one of claims 1 to 13 for the treatment of inflammation of the oral mucosa.

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