Oral compositions and methods of use
Patent Information
- Application Number
- CN202611211033.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2017-12-20
- Filing Date
- 2018-12-14
- Publication Date
- 2026-10-23
Smart Images
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Abstract
Description
[0001] This application is a divisional application of Chinese invention patent application No. 201880082969.4, filed on December 14, 2018, entitled "Oral Composition and Method of Use". Technical Field
[0002] This invention relates to an oral composition and a method of using it. Specifically, this invention relates to an oral composition, and more specifically to an oral composition and method for relieving oral dryness and improving oral health in a subject. Background Technology
[0003] Dry mouth, or paresthesia, is a common condition caused by insufficient saliva production. It is increasingly prevalent among the elderly and is a side effect of many medications and cancer treatments. Severe cases of dry mouth are often associated with salivary gland dysfunction, a condition known as Sjögren's Syndrome.
[0004] The lack of moisture and lubrication normally provided by saliva has a range of negative effects on oral tissues (soft tissues), from mild discomfort to extreme pain and infected mouth ulcers. Persistent discomfort and dryness can also lead to greater health problems by disrupting sleep and impairing people's ability to speak (socially, potentially affecting mental health) and eat (potentially affecting nutrition). Dry buccal tissues have a weaker barrier function and are more easily penetrated by physical irritants such as toxins and carcinogens in food, beverages, and tobacco. There remains a need for compositions that can better alleviate dry mouth. Summary of the Invention
[0005] The present invention discloses compositions comprising, based on the total weight of the compositions, 0.1% to 8% by weight of one or more compounds of formula (I), HOCH2-(CHOH) n -CH2NR 1 R 2 (I) Where R 1 and R 2 Independently selected from hydrogen atoms, alkyl groups, C(O)R 3 and SO2R 4 ;where R 3 and R 4The composition comprises, independently selected from alkyl groups, aryl groups, and aralkyl groups; wherein n is an integer from about 2 to about 5; one or more vegetable oils, from 5% to 95% by weight based on the total weight of the composition; water, from 5% to 80% by weight based on the total weight of the composition; and one or more nonionic aromatic phenolic preservatives, from no more than 1% by weight based on the total weight of the composition, wherein the composition has a pH of 4.5 to 9.5, the composition is an emulsion, and the composition is edible.
[0006] Methods for preventing, inhibiting, disrupting, dispersing, reducing the formation or maintenance of biofilms, or any combination thereof, in oral tissues are also disclosed, the methods comprising contacting the oral tissues with the disclosed composition.
[0007] A method for influencing hydration loss in oral tissues is also disclosed, the method comprising contacting the oral tissues with the disclosed composition.
[0008] A method for influencing the lubrication capacity or lubricity in oral tissues is also disclosed, the method comprising contacting the oral tissues with the disclosed composition.
[0009] A method for influencing oral dryness, dry mouth, or both is also disclosed, the method comprising contacting oral tissue with the disclosed composition.
[0010] The foregoing description is not intended to depict every embodiment of this disclosure. Details of one or more embodiments of this disclosure are also set forth in the following description. Other features, objectives, and advantages of this disclosure will become apparent from the description and the claims. Detailed Implementation
[0011] Saliva is also a primary defense mechanism in the oral cavity against tooth decay. A healthy flow of saliva helps prevent cavities by physically removing bacteria from the mouth before they can adhere to tooth and tissue surfaces and form a protective biofilm. Saliva flow also helps dilute sugars and acids introduced by ingested food and beverages. This buffering capacity neutralizes acids and aids in the digestive process. The presence of calcium salts and phosphates provides a continuous opportunity for enamel remineralization, helping to reverse the decay process.
[0012] Many people with dry mouth use separate products to address both hard tissue health and soft tissue comfort. For soft tissue comfort, saliva substitutes are typically designed to provide lubrication and moisture. These products come in a variety of forms and include thick gels / pastes, sprays, rinses, menthol, and sustained-release tablets. These products are applied daily or as needed for comfort. For hard tissue health, different treatments address cavity prevention directly (antibacterial rinses, fluoride products, calcium / phosphate treatments). "Dry mouth friendly" products, such as toothpaste and mouthwash, are generally recommended. Dry mouth friendly products typically have a neutral pH and are free of alcohol or other irritating ingredients (such as anionic surfactants or emulsifiers).
[0013] The aim is to design a product that effectively addresses the need for relief of dry mouth symptoms (soft tissue comfort) and preventative benefits of oral health (enamel and cavity protection). A fully absorbable two-phase emulsion system is ideally suited for this purpose. It solves the problem of hard tissue health (aqueous phase) and soft tissue comfort (oil phase).
[0014] This document discloses compositions that can be used, for example, in oral compositions. The compositions disclosed herein may include water-in-oil (w / o) emulsions and oil-in-water (o / w) emulsions. W / o (water-in-oil) emulsions consist of water droplets dispersed in a continuous oil phase. In some embodiments, useful compositions may be characterized as crude emulsions. Crude emulsions are kinetically stable mixtures of at least two immiscible liquids, wherein one of the liquids has droplets with a diameter greater than 0.1 µm. Crude emulsions effectively scatter light and therefore appear milky white because their droplets are larger than the wavelength of light.
[0015] The disclosed composition, one or more components in the composition, or both can be characterized as edible. Referring to a component or composition as edible may mean that the specific ingredient or composition is safe for long-term daily intake at recommended levels. In some embodiments, the GRAS (Generally Recognized As Safe) list from the U.S. Food and Drug Administration (FDA) can be used to determine whether a component is edible at the levels used in the composition.
[0016] The disclosed compositions comprise at least one oil, at least one surfactant according to Formula I, and at least one preservative. The amount of water in the disclosed compositions can be characterized by the amount of the aqueous phase in the compositions. The aqueous phase may include components other than water, for example, it may include water-soluble components (as opposed to the oil phase). In some embodiments, the aqueous phase may be no more than 95% by weight, no more than 30% by weight, or no more than 5% by weight based on the total weight of the compositions.
[0017] The disclosed composition also comprises one or more oils. The useful oil can include any oil, but in some embodiments it can include vegetable oils. For example, vegetable oils can be extracted from various plants (e.g., soybeans, low-erucic acid rapeseed, and chili peppers), seeds (e.g., sesame and sunflower), nuts (e.g., walnuts and macadamia nuts), and fruits (e.g., palm, olive, and coconut). In some embodiments, the useful oil can include one or more oils that are liquid at room temperature. The composition can contain a single edible oil, or up to two, three, four, five, or more edible oils. Examples of suitable edible oils may include, but are not limited to, sunflower oil (including high-oleic sunflower oil), safflower oil (including high-oleic safflower oil), olive oil, coconut oil, palm oil, peanut oil, soybean oil, flaxseed oil, rapeseed oil, hemp seed oil, cocoa butter, walnut oil, corn oil, grapeseed oil, sesame oil, peanut oil, wheat germ oil, cottonseed oil, fish oil, watermelon seed oil, lemon oil, orange oil, thistle oil, tomato seed oil, almond oil, perilla oil, low-erucic acid rapeseed oil, pistachio oil, hazelnut oil, avocado oil, camellia seed oil, shea butter, macadamia nut oil, apricot kernel oil, oleic acid, ozone oil, and mixtures or fractions thereof.
[0018] The disclosed compositions may contain no more than 95% by weight, no more than 90% by weight, or no more than 89% by weight of one or more oils based on the total weight of the compositions. The disclosed compositions may also contain no less than 5% by weight, no less than 30% by weight, or no less than 50% by weight of one or more oils based on the total weight of the compositions.
[0019] The disclosed compositions also comprise one or more compounds of formula I: HOCH2-(CHOH) n -CH2NR 1 R 2 (I) Where R 1 and R 2 Independently selected from hydrogen atoms, alkyl groups, C(O)R 3 and SO2R 4 ;where R 3 and R 4 It is independently selected from alkyl groups, aryl groups and aralkyl groups; where n is an integer from about 2 to about 5.
[0020] Group R 1 and R 2 Independently selected from hydrogen atoms, alkyl groups, C(O)R 3 and SO2R 4R 1 and R 2 Each of them can be a hydrogen atom, R 1 and R 2 Each of them can be an alkyl group, R 1 and R 2 Each of them can be C(O)R 3 , or R 1 and R 2 Each of them can be SO2R 4 In some implementations, R 1 It can be a hydrogen atom, and R 2 It can be an alkyl group, C(O)R 3 or SO2R 4 In other implementations, R 1 It can be an alkyl group, and R 2 It can be C(O)R 3 or SO2R 4 In other implementation schemes, R 1 It can be C(O)R 3 And R 2 It can be SO2R 4 When R 1 and R 2 When any one or both of the following are alkyl groups, the alkyl group may contain about one carbon atom, more than about one carbon atom, more than about two carbon atoms, more than about four carbon atoms, more than about six carbon atoms, more than about eight carbon atoms, more than about ten carbon atoms, more than about twelve carbon atoms, more than about fourteen carbon atoms, more than about sixteen carbon atoms, or more than about eighteen carbon atoms. In some embodiments, the alkyl group contains less than about thirty carbon atoms, less than about twenty-six carbon atoms, or less than about twenty carbon atoms. In some embodiments, the alkyl group includes a straight-chain alkyl group. In other embodiments, the alkyl group includes a branched-chain alkyl group. In other embodiments, the alkyl group includes a cycloalkyl group. When R 1 and R 2 When each of them contains an alkyl group, R 1 and R 2 It can contain the same alkyl group, or R 1 and R 2 It may contain different alkyl groups. Non-limiting examples of alkyl groups include methyl, ethyl, 1-propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, neopentyl, hexyl, 2-ethylhexyl, octyl, decyl, undecyl, dodecyl, tetradecyl, pentadecyl, octadecyl, cyclohexyl, 4-methylcyclohexyl, cyclohexylmethyl, cyclopentyl, and cyclooctyl.
[0021] Group R 3and R 4 Independently selected from alkyl groups, aryl groups, and aralkyl groups. When R 3 Or R 4 When any one or both of the following are alkyl groups, the alkyl group may contain about one carbon atom, more than about one carbon atom, more than about two carbon atoms, more than about four carbon atoms, more than about six carbon atoms, more than about eight carbon atoms, more than about ten carbon atoms, more than about twelve carbon atoms, more than about fourteen carbon atoms, more than about sixteen carbon atoms, or more than about eighteen carbon atoms. In some embodiments, the alkyl group contains less than about thirty carbon atoms, less than about twenty-six carbon atoms, or less than about twenty carbon atoms. In some embodiments, the alkyl group includes a straight-chain alkyl group. In other embodiments, the alkyl group includes a branched-chain alkyl group. In other embodiments, the alkyl group includes a cycloalkyl group. In compounds of formula I or pharmaceutically acceptable salts thereof, when R 3 and R 4 When both groups are present, and when R 3 and R 4 When each of them contains an alkyl group, R 3 and R 4 It can contain the same alkyl group, or R 3 and R 4 It may contain different alkyl groups. Non-limiting examples of alkyl groups include methyl, ethyl, 1-propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, neopentyl, hexyl, 2-ethylhexyl, octyl, decyl, undecyl, dodecyl, tetradecyl, pentadecyl, octadecyl, cyclohexyl, 4-methylcyclohexyl, cyclohexylmethyl, cyclopentyl, and cyclooctyl.
[0022] When R 3 Or R 4 When any one or both of the following are aryl groups, the aryl group may contain one or more aromatic rings. The aromatic ring may contain up to six, eight, ten, twelve, fourteen, sixteen, or eighteen carbon atoms. The aromatic ring may contain heteroatoms, such as nitrogen, oxygen, or sulfur. If more than one aromatic ring is present, the aromatic rings may be fused together, or they may be linked by chemical bonds. In compounds of Formula I or their pharmaceutically acceptable salts, when R... 3 and R 4 When both exist, and when R 3 and R 4 When each of them contains an aryl group, R 3 and R 4 It can contain the same aryl group, or R 3 and R 4It may contain different aryl groups. Non-limiting examples of aryl groups include substituted and unsubstituted phenyl, 1-naphthyl, 2-naphthyl, and 9-anthrayl.
[0023] When R 3 Or R 4 When any one or both of the following are aralkyl groups, the aralkyl group may contain one or more aromatic rings. The aralkyl group may contain up to six carbon atoms, up to eight carbon atoms, up to ten carbon atoms, up to twelve carbon atoms, up to fourteen carbon atoms, up to sixteen carbon atoms, up to eighteen carbon atoms, or up to twenty carbon atoms. If more than one aromatic ring is present on the aralkyl group, the aromatic rings may be fused together, or they may be linked by chemical bonds. The aromatic ring may contain heteroatoms, such as nitrogen, oxygen, or sulfur. In compounds of formula I or their pharmaceutically acceptable salts, when R... 3 and R 4 When both groups are present, and when R 3 and R 4 When each of them contains an aryl group, R 3 and R 4 It can contain the same aralkyl group, or R 3 and R 4 It may contain different aralkyl groups. Non-limiting examples of aralkyl groups include benzyl, 1-phenylethyl, 2-phenylethyl, 3-phenylpropyl, 2-naphthylethyl, and 9-anthramethyl.
[0024] In Formula I, n is an integer from about 2 to about 5. In some embodiments, the composition comprises a compound of Formula I or a pharmaceutically acceptable salt thereof, wherein n is an integer having a value of about 5, about 4, about 3, or about 2. In some embodiments, n is an integer having a value of 5, or 4, or 3, or 2. It should be understood that the composition may comprise more than one compound of Formula I or a pharmaceutically acceptable salt thereof, and the compounds may be represented by Formula I with different integer values of n. In these embodiments, the average value of n in the composition may be a non-integer.
[0025] Pharmaceutically acceptable salts include ammonium salts. In some embodiments, the composition comprises an ammonium salt. Ammonium salts can be represented as reaction products of acids and amines, or as reaction products of amines and alkylating agents such as, for example, iodomethane, bromoethane, or benzyl bromide. Ammonium salts include protonated amine compounds, such as those containing NR... 1 R 2 Compounds of formula I whose groups have been protonated by inorganic or organic acids, wherein R 1 and R 2 The groups are independently selected from hydrogen atoms and alkyl groups. Ammonium salts include alkylated amine compounds, such as those containing NR. 1 R 2Compounds of formula I whose groups have been alkylated by an alkylating agent, wherein R 1 and R 2 It is independently selected from hydrogen atoms and alkyl groups.
[0026] Ammonium salts contain at least one counter ion, which can be an inorganic anion, an organic anion, or a combination of anions. Combinations of anions include combinations of more than one inorganic anion, combinations of more than one organic anion, or combinations of inorganic and organic anions. Inorganic ions include, for example, halide ions (fluoride, chloride, bromide, and iodide ions), nitrate, sulfate, tetrafluoroborate, and tetra(aryl)borate. Tetra(aryl)borates include those having the formula Z4B. - Compounds in which Z is an aromatic group, such as a substituted or unsubstituted phenyl group. Examples of tetra(aryl)borates include, but are not limited to, tetraphenylborate, tetra(4-methylphenyl)borate, tetra(2-methylphenyl)borate, tetra(1,3,5-trimethylphenyl)borate, tetra(4-fluorophenyl)borate, tetra(pentafluorophenyl)borate, and tetra(4-trifluoromethylphenyl)borate. Organic anions include, for example, alkylates (such as acetate, propionate, and butyrate), benzoate, fumarate, maleate, tartrate, ascorbate, benzenesulfonate, toluenesulfonate, and citrate. In some embodiments, the pharmaceutically acceptable salt does not contain unsubstituted or substituted cycloheptatrienolone.
[0027] In some embodiments, the ammonium salt can be formed by protonating a compound of formula I using an inorganic acid, an organic acid, or a combination of an inorganic acid and an organic acid, wherein R 1 and R 2 The atom and alkyl group are independently selected. In another embodiment, the ammonium salt can be formed by alkylating a compound of formula I with an alkylating agent, wherein R 1 and R 2 The ammonium salt is independently selected from hydrogen atoms and alkyl groups. In another embodiment, the ammonium salt can be formed by ion exchange or metathesis reaction with a previously formed ammonium salt.
[0028] In some implementation schemes, R 1 and R 2 Each is a hydrogen atom. In some embodiments, the pharmaceutically acceptable salt includes ammonium halides. In some embodiments, the composition comprises a compound of formula II or a pharmaceutically acceptable salt thereof. In some embodiments, the salt comprises ammonium halides. In one specific embodiment, the ammonium halide comprises ammonium chloride.
[0029] HOCH2-(CHOH)4-CH2NH2 (II)
[0030] In some implementation schemes, R 1Includes alkyl groups, and R 2 For C(O)R 3 , where R 3 Includes alkyl groups. In some embodiments, R 1 Includes alkyl groups having about one to about four carbon atoms, and R 3 Includes alkyl groups having about four to about sixteen carbon atoms. In some embodiments, R 1 Includes methyl groups, and R 3 It includes alkyl groups having seven, eight, or nine carbon atoms. In some embodiments, the composition comprises a compound of formula III, IV, or V.
[0031]
[0032] In some implementation schemes, R 1 It is a hydrogen atom, and R 2 Including alkyl groups. In some embodiments, the pharmaceutically acceptable salt includes ammonium halides. In some embodiments, the alkyl group comprises about one to about eight carbon atoms. In some embodiments, the dental composition comprises a compound of formula VI or a pharmaceutically acceptable salt thereof. The salt may include ammonium halides. In some embodiments, the ammonium halide comprises ammonium chloride. In some embodiments, the dental composition comprises a compound of formula VII or a pharmaceutically acceptable salt thereof. The salt may include ammonium halide. In some embodiments, the ammonium halide comprises ammonium chloride. In some embodiments, R... 1 and R 2 Independently includes an alkyl group having about one to about eight carbon atoms. In some embodiments, the dental composition comprises a compound of formula VIII or a pharmaceutically acceptable salt thereof. The salt may include ammonium halides. In some embodiments, the ammonium halide comprises ammonium chloride.
[0033]
[0034] It is recognized that the various compounds include chiral carbon atoms. For simplicity, the stereochemical configuration of each chiral carbon atom is not specified in the various formulas. This is intended so that formulas I-VIII, as used in this specification and claims, represent each compound having any possible stereochemical configuration. In some embodiments, the compounds of formulas II to VIII are aminoglycosides and their derivatives, respectively having the common names D-glucosamine, N-methyl-N-octanoyl-D-glucosamine (“MEGA-8”), N-methyl-N-nonanoyl-D-glucosamine (“MEGA-9”), N-methyl-N-decanoyl-D-glucosamine (“MEGA-10”), N-methyl-D-glucosamine, N-octyl-D-glucosamine, and N-methyl-N-octyl-D-glucosamine.
[0035] The disclosed compositions may comprise no more than 8% by weight of one or more compounds of Formula I, no more than 7% by weight of one or more compounds of Formula I, or no more than 6% by weight of one or more compounds of Formula I, based on the total weight of the composition. In some embodiments, the disclosed compositions may comprise no less than 0.1% by weight of one or more compounds of Formula I, no less than 1% by weight of one or more compounds of Formula I, no less than 2% by weight of one or more compounds of Formula I, or no less than 4% by weight of one or more compounds of Formula I, based on the total weight of the composition.
[0036] The disclosed compositions also contain one or more preservatives. Exemplary available preservatives may include nonionic aromatic phenolic preservatives. Specific exemplary available preservatives may include mixtures of propylparaben, thymol, gluconolactone, and sodium benzoate (such as GEOGARD ECT from Lonza Group Ltd, Switzerland). ™ ).
[0037] The disclosed compositions may contain no more than 0.8% by weight of one or more nonionic aromatic phenolic preservatives, no more than 0.6% by weight of one or more nonionic aromatic phenolic preservatives, or no more than 0.1% by weight of one or more nonionic aromatic phenolic preservatives based on the total weight of the composition. In some embodiments, the disclosed compositions may contain no less than 0.1% by weight of one or more nonionic aromatic phenolic preservatives, no less than 0.6% by weight of one or more nonionic aromatic phenolic preservatives, or no less than 0.8% by weight of one or more nonionic aromatic phenolic preservatives based on the total weight of the composition.
[0038] The disclosed compositions may optionally contain additional components in addition to those described above. Exemplary optional components may include, for example, sweeteners, humectants, mineral salts, buffering components, flavoring agents, preservatives, prebiotics, probiotics, or combinations thereof. It may also contain appropriate levels of other optional beneficial ingredients, such as aloe vera (multiple benefits), folic acid (related to B12), hyaluronic acid (lubricating, healthy skin), octylpyranoside, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-glucosamine hydrochloride, D-glucosamine sulfate, D-glucosamine, N-methyl-D-glucosamine, N-ethyl-D-glucosamine, N-octyl-D-glucosamine, glycine, nonanoic acid, ethyl caprylate, DMSO, ceramides (healthy skin), arginine, betaine or oxyglycerides, vitamin E (antioxidant and preservative), vitamin B12 (healthy skin, etc.), EDTA, cetylpyridinium chloride, chlorhexidine, other antibacterial agents, etc., or combinations thereof.
[0039] In some embodiments, the disclosed compositions may contain flavoring agents, including, for example, peppermint, strawberry, butter, vanilla, coconut, almond, bubblegum, berry, fruit juice, caramel, caramel, or combinations thereof. In some embodiments, flavoring agents such as mint, citrus, etc., may also be advantageous because they stimulate saliva production when used in the composition. Artificial sweeteners (e.g., stevia, aspartame, sucralose, neotame, acesulfame potassium (Ace-K), saccharin, and advantame) may also be used. In some embodiments, the disclosed compositions may contain one or more sweeteners, including, for example, non-cariogenic polyols or sugar substitutes (e.g., sucralose). In some embodiments, the disclosed compositions may contain non-cariogenic polyol sweeteners such as xylitol, sorbitol, maltitol, erythritol, mannitol, isomaltitol, or combinations thereof. In compositions containing optional sweeteners, the sweetener may be present in an amount of not less than 1% by weight or not less than 0.5% by weight based on the total weight of the composition. In some embodiments, the optional sweetener may be present in an amount of not more than 25% by weight, not more than 20% by weight, or not more than 15% by weight based on the total weight of the composition.
[0040] In some embodiments, the disclosed compositions may contain one or more wetting agents, including, for example, glycerin, propylene glycol, or sucrose, or combinations thereof. In some embodiments, the disclosed compositions may contain glycerin as a wetting agent. In compositions containing optional wetting agents, one or more wetting agents may be present in an amount of not less than 2.5% by weight, not less than 5% by weight, or not less than 10% by weight based on the total weight of the composition. In compositions containing optional wetting agents, one or more wetting agents may be present in an amount of not more than 40% by weight, not more than 60% by weight, or not more than 80% by weight based on the total weight of the composition.
[0041] In some embodiments, the disclosed compositions may optionally comprise one or more minerals that are useful or beneficial to ingestion or oral health. Exemplary optional minerals that may be included in the disclosed compositions may include calcium (Ca), phosphorus (P), magnesium (Mg), fluorine (F), iron (Fe), strontium (Sr), zinc (Zn), potassium (K), or combinations thereof. In some embodiments, some minerals may be provided by comprising magnesium chloride (MgCl2), calcium chloride (CaCl2), strontium chloride, zinc chloride, zinc gluconate, potassium nitrate, dipotassium hydrogen phosphate (KH2PO4), or combinations thereof. In some embodiments containing fluorine, it may be included as fluoride ions (F-) in salt form (MgF2, CaF2, etc.).
[0042] In some embodiments, the disclosed compositions may contain one or more preservatives to give the composition microbial stability, increase its microbial stability, or some combination thereof. In some embodiments, useful preservatives include those that function at neutral pH, do not adversely affect taste, are edible, and are effective against a variety of pathogens, or combinations thereof. Specific exemplary available preservatives may include GEOGARD. ® Preservatives, which are commercially available from Lonza, Basel, Switzerland, include, for example, salicylic acid, benzyl alcohol, sodium benzoate, potassium sorbate, parabens, natural preservatives, polyglycerol esters, glyceryl monolaurate, 1,2-octanediol, caprylic / capric triglycerides, DHA, aloe vera, potassium sorbate, CPC, PHMB, CHG, vitamin E, triethyl citrate, and EDTA. Specific examples of GEOGARD preservatives include: GEOGARD ECT [benzyl alcohol (77%-86%), salicylic acid (8%-15%), glycerin (3%-5%), and sorbic acid (1%-4%)]; and GEOGARD 221 [dehydroacetic acid (7.7%-8.3%), benzyl alcohol (85%-89%), and water (4%).
[0043] In some embodiments, the disclosed compositions may contain one or more naturally occurring amino acids as agents to help prevent tooth decay. "Tooth decay" is understood as cavities, which cause tooth demineralization. The following amino acids have been found to be useful as anti-caries agents: glycine, leucine, isoleucine, lysine, methionine, phenylalanine, serine, threonine, valine, tryptophan, and mixtures thereof; sometimes the following amino acids are preferred: glycine, phenylalanine, serine, isoleucine, leucine, and methionine; sometimes even more preferred are glycine and phenylalanine. The amino acids may be natural or synthetic. The amino acids may be in the D-configuration or L-configuration. In some embodiments, the L-configuration is preferred.
[0044] In some embodiments, the disclosed composition may contain amino acids present in amounts (by weight % of the total composition): at least 0.1% by weight, at least 1% by weight, or at least 2% by weight. In some embodiments, the disclosed composition may contain amino acids present in amounts (by weight % of the total composition): not more than 15% by weight, not more than 12% by weight, or not more than 10% by weight. In some embodiments, the disclosed composition may contain amino acids present in amounts (by weight % of the total composition): including and in the range of 0.1% by weight to 15% by weight, including and in the range of 1% by weight to 12% by weight, or including and in the range of 2% by weight to 10% by weight.
[0045] In some embodiments, the disclosed composition comprises the following amino acids, alone or in combination with other amino acids: 0.1% to 10% by weight of glycine; or 0.1% to 5% by weight of leucine; or 0.1% to 5% by weight of isoleucine; or 0.1% to 10% by weight of lysine; or 0.1% to 10% by weight of methionine; or 0.1% to 5% by weight of phenylalanine; or 0.1% to 10% by weight of serine; or 0.1% to 10% by weight of threonine; or 0.1% to 8% by weight of valine; or 0.1% to 2% by weight of tryptophan; all of the above are expressed as a percentage by weight relative to the total weight of the composition.
[0046] In some embodiments, the disclosed composition comprises the following concentrations of amino acids, alone or in combination with other amino acids: 1% to 10% by weight of glycine; or 1% to 5% by weight of leucine; or 2% to 5% by weight of isoleucine; or 5% to 10% by weight of lysine; or 2% to 10% by weight of methionine; or 1% to 5% by weight of phenylalanine; or 1% to 10% by weight of serine; or 6% to 10% by weight of threonine; or 3% to 8% by weight of valine; or 0.5% to 2% by weight of tryptophan; all of the above are expressed as a percentage by weight relative to the total weight of the composition.
[0047] In contrast, the following amino acids were found to be ineffective in preventing tooth decay: proline, arginine, histidine, aspartic acid, glutamine, and tyrosine. Some embodiments of the disclosed compositions do not contain these amino acids: proline, arginine, histidine, aspartic acid, glutamine, and tyrosine. Some embodiments of the disclosed compositions contain these amino acids only in amounts not exceeding 0.5% by weight, or exceeding 0.3% by weight, or exceeding 0.1% by weight relative to the total composition.
[0048] In some embodiments, the disclosed compositions do not contain any quaternary ammonium compounds.
[0049] The disclosed compositions may have varying properties. In some embodiments, the disclosed compositions can be described by their pH, viscosity, stability, a variety of other properties, or combinations thereof.
[0050] In some embodiments, the disclosed composition may have a pH acceptable for use in the human oral cavity, for example. In some embodiments, the disclosed composition may have a pH of, for example, 4.5 to 9.5. In some embodiments, the pH of the composition may be in a more neutral range, for example, 5.0-8.5 or 5.5-8.5, because patients with dry mouth may be more sensitive to pH. The composition may have such a pH naturally, or it may be buffered to have a pH in a useful, for example, “neutral” range.
[0051] In some embodiments, the disclosed compositions may optionally contain one or more acid neutralizers / buffers that are useful for or beneficial to oral health in reducing acid erosion of teeth. Such compositions have the ability to buffer or neutralize acids in the oral cavity to reduce acid corrosion.
[0052] In some implementations, the acid buffer may contain any basic substance that dissociates in water (i.e., an aqueous alkaline solution) to generate one or more hydroxyl ions, or may contain any substance that can accept protons or has non-shared electron pairs.
[0053] In some embodiments, the acid buffer or neutralizing agent may comprise carbonates, bicarbonates, chlorides, hydroxides, citrate diphosphates, sulfates, etc., typically in the form of salts. Exemplary salts include complexes of sodium, potassium, calcium, ammonium, aluminum, magnesium, etc. In some other embodiments, the acid buffer may comprise sodium carbonate, potassium carbonate, calcium carbonate, ammonium bicarbonate, ammonium carbonate, ammonium chloride, ammonium hydroxide, diammonium hydrogen citrate, ammonium phosphate (monobasic or dibasic), ammonium sulfate, aluminum carbonate, aluminum hydroxide, calcium citrate, calcium hydroxide, magnesium carbonate, magnesium hydroxide, magnesium phosphate (dibasic), potassium hydroxide, potassium bicarbonate, etc.
[0054] In some embodiments, the acid buffer or neutralizing agent may comprise a phosphate-based buffer containing PO4. 3- Anion-containing buffers (e.g., sodium phosphate, potassium phosphate, calcium phosphate, and ammonium phosphate), containing HPO4. 2- Anion-containing (e.g., sodium hydrogen phosphate, potassium hydrogen phosphate, and calcium hydrogen phosphate) dihydrogen phosphate buffer, the dihydrogen phosphate buffer containing H2PO4 - Anion-containing (e.g., sodium dihydrogen phosphate, potassium dihydrogen phosphate, and calcium dihydrogen phosphate) carboxylate-based buffers containing RCOO - Anionic (e.g., sodium acetate, sodium citrate, potassium acetate, ammonium acetate, and ammonium citrate) carbonate-based buffers containing CO32- 2- Anions (e.g., sodium carbonate, calcium carbonate, magnesium carbonate, ferric carbonate, potassium carbonate, and ammonium carbonate), bicarbonate buffer containing HCO3- - Anions (e.g., sodium bicarbonate, calcium bicarbonate, ammonium bicarbonate, and potassium bicarbonate).
[0055] In some embodiments, the disclosed composition may have a viscosity that makes it suitable for use as a sprayable composition or for delivery as a sprayable composition. The composition can be sprayed, for example, via a non-pressurized dispenser or a pressurized pump dispenser. In some embodiments, the disclosed composition may have a viscosity such that it can be delivered as a mist spray via a non-pressurized dispenser. In some embodiments, the disclosed composition may have a viscosity of not more than 150,000 centipoise (cps), not more than 100,000 cps, not more than 50,000 cps, or not more than 20,000 cps. In some embodiments, the disclosed composition may have a viscosity of not less than 2,500 centipoise (cps), not less than 5,000 cps, or not less than 7,500 cps.
[0056] In some embodiments, the disclosed compositions are more viscous and can be delivered as a paste, smear, or pumpable lotion or cream. In some such embodiments, a viscosity of up to 2,000,000 cps may be useful. In some embodiments, the disclosed compositions may be solid or emulsified in a solid form. Some high-viscosity sprays may also be delivered in other forms. In some specific exemplary embodiments, tablets, solid sticks (e.g., lipsticks), or other similar types of these forms may be used.
[0057] In some embodiments, the disclosed compositions may have desired stability properties. The stability of the composition may include microbial stability, physical stability, or a combination thereof. In some embodiments, the disclosed compositions are microbiologically stable for at least 6 months, in some embodiments for 1 year, and in some embodiments for more than 2 years.
[0058] In some embodiments, for example, the disclosed composition remains physically stable when subjected to normal room temperature conditions, when subjected to temperatures approaching or exceeding the freezing point of the composition and subsequently thawing, or a combination of these conditions. In some embodiments, for example, the composition may be stable if it does indeed remain physically stable when subjected to normal room temperature conditions, when subjected to temperatures approaching or exceeding the freezing point of the composition and subsequently thawing, or a combination of these conditions. In some embodiments, the disclosed composition is physically stable when subjected to temperatures above room temperature, for example, greater than 60°C. In some embodiments, the disclosed composition is physically stable, for example, when subjected to mechanical forces (e.g., gravity) such as centrifugation. In some embodiments, the disclosed composition is physically stable, for example, when subjected to changes in both temperature (such as those discussed above) and mechanical forces (such as those discussed above). In some embodiments, a physically stable composition is one that does not separate into an oil phase and an aqueous phase during the product's service life, during transportation and / or storage, or any combination thereof.
[0059] In some embodiments, the disclosed composition is physically stable upon undergoing at least one freeze / thaw / centrifugation cycle. A freeze / thaw / centrifugation cycle comprises freezing the composition (e.g., for at least 3 hours), followed by thawing the composition (e.g., for at least 2 hours), and then centrifuging the composition at 1750 rcf for 15 minutes. In some embodiments, the disclosed composition is physically stable, for example, upon undergoing at least two or at least three freeze / thaw / centrifugation cycles. In some embodiments, the disclosed composition is physically stable upon undergoing temperatures above 60°C (which may be referred to as a thermal cycle). In some embodiments, the disclosed composition is physically stable upon undergoing at least one thermal cycle. In some embodiments, the disclosed composition is physically stable upon undergoing at least one freeze / thaw / centrifugation cycle followed by a heating cycle.
[0060] In some embodiments, the disclosed compositions may have desired effects when used. Such effects may include, for example, the effect of the composition on biofilms, the effect of the composition on plaque buildup, the effect of the composition on dehydration, the composition's ability to maintain or provide lubricating properties, resistance to dilution or rinsing by saliva or water, or general drinking and eating abilities, or combinations thereof.
[0061] In some embodiments, the disclosed composition can prevent, inhibit, disrupt, disperse, or reduce the formation or maintenance of biofilm in areas in contact with the composition. In some embodiments, the composition can prevent, inhibit, disrupt, disperse, or reduce the formation or maintenance of biofilm in the mouth when applied to a user's mouth, compared to a mouth without the composition applied. In some embodiments, the composition can prevent, inhibit, disrupt, disperse, or reduce the formation or maintenance of biofilm in a container where a biofilm is present and the composition is applied, compared to a container without the composition applied. Prevention, inhibition, disruption, dispersion, reduction, or control of biofilm formation or maintenance, or combinations thereof, can be measured using a modified MBEC assay (described in ASTM E2799), which measures the growth of *Streptococcus mutans* (a type of bacteria) on specific nails in a microtiter plate. Streptococcus mutansBiofilm disruption. Biofilms growing on the nails are treated by periodically immersing them in test material and then washing them with saliva and water. The biofilm remaining on each nail after treatment can be quantified by measuring the amount of fluorescently labeled bacteria eluted from the nails at the end of the treatment cycle (see Examples). In some embodiments, the disclosed composition can affect plaque accumulation in areas in contact with the composition. The areas in contact can be in vivo or in vitro. In some embodiments, the composition reduces plaque accumulation on at least one tooth in the mouth when applied to a user's mouth, compared to a mouth without the composition applied. In some embodiments, the composition reduces plaque accumulation in containers where plaque can grow and the composition is applied, compared to a container without the composition applied. Reduced plaque accumulation can be measured by various in vivo methods, including, for example, plaque scoring, plaque staining, etc.
[0062] In some embodiments, the disclosed composition can affect hydration loss in areas in contact with the composition. The areas in contact can be in vivo or in vitro. In some embodiments, the composition can reduce hydration loss in the mouth when applied to a user's mouth, compared to a mouth without the composition applied. In some embodiments, the composition can reduce hydration loss from tissues where hydration is likely to be lost and to which the composition is applied, compared to tissues without the composition applied. Hydration loss can be measured by exposing uniformly sized treated tissues to a controlled 37°C environment for a set period of time (4 hours) and recording the % weight loss of the treated tissue sample. The treated tissues are then exposed to high temperatures to remove all water from the sample (95°C / 4 hours and 115°C / 4 hours). The water loss at 4 hours is divided by the total water loss (after the 115°C step) to represent the water lost from the tissue at 4 hours. In some embodiments, the disclosed composition can affect less than 65% or less than 60% of the water loss.
[0063] In some embodiments, the disclosed composition can affect the lubricity or lubricity of areas in contact with the composition. The areas in contact can be internal or external. In some embodiments, the composition, when applied to a user's mouth, can maintain or increase lubricity in the mouth, compared to a mouth without the composition applied. In some embodiments, the composition can, for example, provide the same level of lubrication properties to the mouth as saliva can provide. In some embodiments, the composition can maintain or increase lubricity on a substrate where lubrication may be lost and the composition is applied, compared to a substrate without the composition applied. Lubricity or the ability to provide lubrication properties can be measured by the coefficient of friction relative to a suitable substrate. A low coefficient of friction (compared to saliva) is desirable.
[0064] The disclosed compositions combine the benefits of both oil and aqueous phases. In some embodiments, the disclosed compositions can combine many desired benefits, such as lubrication, moisturizing, hard tissue exposure to beneficial minerals, and pH balance. Finding an uptakeable surfactant and thickening system to achieve all the desired benefits requires extensive experimental research, and is not limited to routine optimization. Furthermore, some of the disclosed compositions achieve the desired physical stability. Emulsions without certain physical stability standards may have lower-than-expected product shelf life and commercial usability. Stability during freeze / thaw cycles may be important to ensure the stability of the emulsion during storage and transportation. Commercially, it may not be desirable for the emulsion to separate into aqueous and oil phases prior to oral administration. The unique combination of surfactants and thickeners disclosed produces emulsion compositions that are physically stable for multiple cycles of freeze / thaw / centrifugation challenge tests and may resist separation when exposed to elevated temperatures (>60°C). Surprisingly, some of these formulations also possess anti-plaque properties, such as those against Streptococcus mutans (S. mutagenesis). Streptococcus mutans This was demonstrated in an in vitro anti-biofilm study of (a well-known biofilm-forming bacterium that causes dental plaque).
[0065] This document also discloses methods of using the disclosed compositions. The disclosed methods may include contacting the oral cavity or oral tissues with the disclosed compositions. The step of contacting the oral cavity or oral tissues may be accomplished by applying the compositions in any manner. The disclosed methods may be used to prevent, inhibit, disrupt, disperse, reduce, control the formation or maintenance of biofilms, or any combination thereof, in areas in contact with the compositions; to influence hydration loss in areas in contact with the compositions; to influence the lubricity or lubricity of areas in contact with the compositions; and to influence or alleviate dry mouth, syphilis, or both.
[0066] Unless otherwise specified, all scientific and technical terms used herein have their common meaning in the art. The definitions provided herein will aid in understanding certain terms frequently used herein and are not intended to limit the scope of this disclosure.
[0067] Unless otherwise expressly stated, the singular forms “a,” “an,” and “described” as used in this specification and the appended claims cover embodiments having multiple referents.
[0068] Unless otherwise expressly stated, the term "or" as used in this specification and the appended claims is generally used in its meaning as including "and / or". The term "and / or" means one or all of the listed elements, or any combination of two or more of the listed elements.
[0069] As used herein, the terms “having,” “including,” and “comprising” are used in their open-ended sense and generally mean “including, but not limited to.” It should be understood that “consistently composed of,” “composed of,” etc., are included within “including,” etc. For example, a composition “comprising” silver can be a composition “composed of silver” or “consistently composed of silver.”
[0070] As used herein, when “consistently made of” refers to a composition, apparatus, system, method, etc., it means that the constituent elements of such composition, apparatus, system, method, etc. are limited to the enumerated constituent elements and any other constituent elements that do not substantially affect the essential and novel characteristics of such composition, apparatus, system, method, etc.
[0071] The terms "preferred" and "ideally" refer to embodiments that provide certain beneficial effects under certain circumstances. However, other embodiments may also be preferred under the same or other circumstances. Furthermore, the description of one or more preferred embodiments does not imply that other embodiments are unavailable, nor is it intended to exclude other embodiments from the scope of this disclosure (including the claims).
[0072] Additionally, in this document, the numerical range expressed by endpoints includes all values contained within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, 5, etc., or 10 or less includes 10, 9.4, 7.6, 5, 4.3, 2.9, 1.62, 0.3, etc.). When the range of values is "up to" a particular value, that value is included within that range.
[0073] The use of "first," "second," etc., in the above description and the following claims is not necessarily intended to indicate the existence of an enumerated number of objects. For example, the "second" basis is only intended to distinguish it from another basis (such as the "first" basis). The use of "first," "second," etc., in the above description and the following claims is also not necessarily intended to indicate that one is earlier than the other in time.
[0074] Exemplary articles and techniques based on this disclosure will be illustrated by the following non-limiting embodiments.
[0075] Example
[0076] Table 1A: Materials
[0077]
[0078]
[0079] Table 1B: Commercially available products for the treatment of dry mouth
[0080]
[0081] Table 1C: Commercially available products for the treatment of dry mouth
[0082]
[0083] Example Preparation Process
[0084] The formulations of the examples were prepared as follows: The aqueous phase components were mixed together by dissolving them completely in water. The aqueous phase was stirred at room temperature (approximately 25°C) for about 15 minutes to dissolve all components. Next, oil was added to the prepared aqueous phase, and stirring was continued at room temperature for another 3 hours.
[0085] Table 4A: Examples EX.1-EX.5
[0086]
[0087] Table 4B: Examples EX.6-EX.8
[0088]
[0089] Table 4C: Examples EX.9 - EX.12
[0090]
[0091] Table 4D: Examples EX.13 - EX.16
[0092]
[0093] Table 4E: Examples EX.17 - EX.18
[0094]
[0095] Preparation of aqueous solution A
[0096] Aqueous solution A was prepared as the stock solution for preparing EX.19-EX.23.
[0097] Table 4F: Aqueous Solution A
[0098]
[0099] Table 4G: Examples EX.19 - EX.23
[0100]
[0101] In vitro hydration retention test method (thermogravimetric analysis of water retention)
[0102] The percentage of weight loss of the samples was determined using a LECO thermogravimetric analyzer (TGA) to simulate 4 hours of hydration (moisture) retention in the oral cavity. In this in vitro test, thin slices of roasted raw beef (approximately 6 mm thick) were used to simulate soft tissue. A 1 cm diameter section was taken from the roasted raw beef slice using a circular biopsy puncturist to obtain disc-shaped tissue section samples. These samples were pre-weighed and then coated by immersing the tissue samples in one of commercially available oral dryness relief products or formulations of the example. Uncoated beef samples were also analyzed as a control. Approximately 0.2 g of the test material was weighed into a foil-lined analytical container and placed in the LECO TGA thermogravimetric analyzer. The example was then held at body temperature (37°C) for 4 hours, and the percentage (%) of volatile matter (water) loss after this step was recorded. Next, the temperature was increased to evaporate all volatile matter and the total weight fraction was obtained. The weight loss at the 4-hour step point at 37°C was divided by the total volatile matter and expressed as the percentage (%) of total volatile matter lost at 4 hours. The following shows the detailed information of the time / temperature profile used to run the program on the LECO TGA thermogravimetric analyzer.
[0103] Table 5: LECO TGA Program
[0104]
[0105] Summary of in vitro hydration retention test results
[0106] Data for commercially available products and formulations of the examples are summarized in Tables 6A, 6B, and 6C below, reflecting three separate analytical dates. Lower values for the percentage of volatile matter loss are expected. Lower values for the percentage of volatile matter loss indicate that the treatment formulation promotes greater moisture retention, which is the desired effect of the oral drying treatment composition.
[0107] Table 6A: Results of In Vitro Hydration Retention Test
[0108]
[0109] Table 6B: Results of In Vitro Hydration Retention Test
[0110]
[0111] Table 6C: Results of In Vitro Hydration Retention Test
[0112]
[0113] Viscosity testing methods
[0114] The viscosity of the example formulations was measured at room temperature using a parallel plate fixture on an AR-G2 electromagnetic bearing rheometer from TA Instruments Ltd. Approximately 1.4 mL of the example formulation was placed between the plates, with the plate gap set to 1 mm for measurement at room temperature. Viscosities were recorded at shear rates of 1.0, 3.162, and 10 1 / s. Each formulation was measured twice in parallel, and the average value was recorded.
[0115] Table 7: Viscosity Test Results
[0116]
[0117] Friction test method : Friction / lubrication was measured using a FORCEBOARD universal friction tester (Industrial Dynamics, Sweden AB) equipped with a 10 Newton (N) load sensor. A natural lambskin condom made from sheep cecum (Trojan NATURALAMB) was used. ™Luxury condoms (Church & Dwight Co., Inc., Ewing, NJ) are used to simulate oral mucosal tissue. Before use and between measurements, the condom should be thoroughly rinsed to remove excess liquid, ensuring no residual lubricant or example test preparation may interfere with subsequent measurements. Place the condom on a glass slide, smoothing it to remove wrinkles, and then secure it to the FORCEBOARD friction tester using a stapler. Using a syringe, meter 0.5 mL of the example test solution (or other comparative sample such as water or human saliva) onto the surface of the condom closest to the front of the FORCEBOARD (farthest from the engine). Then, secure a second layer of condom around a gloved finger and move the covered finger downwards along the surface of the FORCEBOARD (towards the engine) while applying a target vertical force of 3 N. Repeat this movement 6–10 times for each parallel measurement. The coefficient of friction (under vertical forces of 2.9 to 3.1 N) was calculated using FORCEBOARD analysis software (Industrial Dynamics, Sweden). A lower coefficient of friction results in a smoother surface, which is therefore an ideal property for formulations used to treat dry mouth.
[0118] Table 8: Friction Test Results
[0119]
[0120] Biofilm damage testing methods
[0121] This method utilizes a high-throughput MBEC assay system (Innovotech, Calgary, Alberta, Canada). The method assesses the efficacy of a treatment in disrupting biofilms by quantifying the amount of fluorescently labeled biofilm remaining on the MBEC inoculator nail after exposure to the relevant treatment conditions. This assay is similar to ASTM E2799-12 (using...). MBEC ™ The standard method for testing the disinfection efficacy of biofilms against Pseudomonas aeruginosa was modified to use Streptococcus mutans as the relevant organism, and an improved protocol was used to expose the biofilm to the test material.
[0122] MBEC Measurement Procedure : Overnight cultures of *Streptococcus mutans* (ATCC 25175) were prepared by introducing a small amount of frozen stock solution into 5 mL of brain heart infusion (BHI) broth in a 15 mL conical tube using a sterile inoculation loop. The tubes were incubated at 37°C (stationary, without shaking) for 12–16 hours. The density of the overnight culture was estimated by turbidity measurement (OD600), and the culture was further incubated with 1% sucrose and 1 μM Alexa Fluor. ® 488 glucan – 10,000 MW (Molecular Probes) ® Dilute PN / D22910 in BHI medium to an appropriate OD600 of 0.01 to obtain an appropriate volume of inoculum for filling the required 96-well plates. Add 150 µL of inoculum to the 96-well MBEC plate. ™ Biofilm inoculant plate (Innovotech) ® P&G (polystyrene) plates were inoculated into appropriate wells. MBEC inoculator caps (with nails immersed in each well) were placed on the inoculation plate. The plate was wrapped in a paraffin film and incubated in a sealed plastic container, which was humidified by lining the bottom with a damp paper towel (37°C, shaken at 250 RPM). The biofilm was allowed to form on the nails for 4 hours before being exposed to the formulation of the example. In this modified assay, the biofilm grown on the nails was exposed to the formulation of the example twice during the assay, at 7 and 18 hours post-inoculation. Exposure to the formulation of the example was performed as a treatment cycle, with additional washing steps in water. Treatment was performed by transferring the nails to multiple 96-well plates filled with either 150 μL / well of the formulation of the example or 150 μL / well of water.
[0123] Process the cycle steps (executed at 7 and 20 hours).
[0124] 1) Expose to the test material for 1 minute (150 μL / well)
[0125] 2) Rinse with water for 1 minute (200µL / well)
[0126] 3) Rinse with water for 1 minute (200µL / well)
[0127] 4) Rinse with water for 1 minute (200µL / well)
[0128] After rinsing with water, the nails were placed back into the growth medium (BHI + 1% sucrose + 1µM Alexa Fluor). ®488 glucan (10,000 MW) was placed in a 96-well plate and returned to the incubator to allow additional biofilm buildup until the next treatment or until the end of the final growth phase. After the last treatment exposure cycle (20 hours post-inoculation), the pins were incubated in growth medium for another 4 hours, then transferred to a final wash plate for 1 minute (150 µL of sterile water per well, agitated at 37°C for final rinsing), followed by transfer to 150 µL / well of 50 U / mL glucanase (pH 5.5) (from Penicillium spp., Sigma) filled with 0.2 M acetate. ® In 96-well plates (black plates, suitable for fluorescence quantification in a plate reader) of D4668-1KU, pins were incubated in the extraction solution wells by shaking at 37°C for 30 minutes at 250 RPM. The plate was then placed in an ultrasonic water bath at room temperature for at least 1 hour to elute the accumulated biofilm from the pins into the dextranase / acetate solution. After sonication, fluorescence in each well was read in a fluorescence plate reader (excitation = 488 nm, emission = 525 nm). Each treatment was performed in parallel with 4–8 wells.
[0129] A control solution of 0.1% CHG (chlorhexidine gluconate) in water was prepared by diluting a 20% w / v CHG aqueous solution in water. The biofilm disruption of this 0.1% CHG solution was also analyzed as a comparative control.
[0130] Results of biofilm damage test method
[0131] Table 9 shows the mean relative fluorescence readings for each formulation treatment tested. Lower values indicate higher biofilm disruption activity than higher values. Values are recorded as relative fluorescence (%), normalized relative to the mean fluorescence value of wells containing PBS as a negative control. For consistency, appropriate parallel assays were run in PBS-treated wells for each MBEC plate. Data were normalized using a PBS control run on the same 96-well plate.
[0132] Table 9: Results of Biofilm Disruption Tests
[0133]
[0134] Exemplary Implementation : 1. A composition comprising: Based on the total weight of the composition, 0.1% to 8% by weight of one or more compounds of formula (I) HOCH2-(CHOH) n -CH2NR 1 R 2 (I) Where R 1 and R 2 Independently selected from hydrogen atoms, alkyl groups, C(O)R 3 and SO2R 4 ;where R 3 and R 4 Independently selected from alkyl groups, aryl groups, and aralkyl groups; where n is an integer from about 2 to about 5; One or more vegetable oils, based on 5% to 95% by weight of the total weight of the composition; Based on the total weight of the composition, 5% to 80% water, and One or more nonionic aromatic phenolic preservatives, based on the total weight of the composition, are present in an amount of 0.01% to 1% by weight. The composition has a pH of 4.5 to 9.5, is an emulsion, and is edible.
[0135] 2. The composition according to Clause 1, wherein R1 and R2 are independently selected from hydrogen atoms, alkyl groups and C(O)R3, wherein at least one of R1 and R2 is C(O)R3, and R3 is selected from alkyl groups having seven carbon atoms, alkyl groups having eight carbon atoms and alkyl groups having nine carbon atoms.
[0136] 3. The composition according to any one of clauses 1 to 2, wherein n is 4.
[0137] 4. The composition according to any one of clauses 1 to 3, wherein 1% to 2% by weight of formula I is present.
[0138] 5. The composition according to Clause 2, wherein R 3 It is an alkyl group having eight carbon atoms.
[0139] 6. The composition according to any one of Clauses 1 to 5, wherein the one or more edible vegetable oils are selected from: sunflower oil, safflower oil, olive oil, coconut oil, palm oil, peanut oil, soybean oil, flaxseed oil, rapeseed oil, linseed oil, hemp seed oil, cocoa butter, walnut oil, corn oil, grapeseed oil, sesame oil, peanut oil, wheat germ oil, cottonseed oil, fish oil, watermelon seed oil, lemon oil, orange oil, thistle oil, tomato seed oil, almond oil, perilla oil, low erucic acid rapeseed oil, pistachio oil, hazelnut oil, camellia seed oil, shea butter, macadamia nut oil, apricot kernel oil, oleic acid, and avocado oil.
[0140] 7. The composition according to any one of Clauses 1 to 6, wherein the one or more edible vegetable oils are 75% to 95% by weight based on the total weight of the composition.
[0141] 8. The composition according to any one of Clauses 1 to 7, wherein the one or more nonionic aromatic phenolic preservatives are selected from propylparaben, thymol, a mixture of individual preservatives comprising 77%-86% benzyl alcohol, 8%-15% salicylic acid, 3%-5% glycerin and 1%-4% sorbic acid, or combinations thereof.
[0142] 9. The composition according to any one of Clauses 1 to 7, wherein the one or more nonionic aromatic phenolic preservatives are present in an amount not exceeding 0.8% by weight based on the total weight of the composition.
[0143] 10. The composition according to any one of Clauses 1 to 8, wherein the one or more nonionic aromatic phenolic preservatives are present in an amount not greater than 0.6% by weight based on the total weight of the composition.
[0144] 11. The composition according to any one of Clauses 1 to 10, wherein the composition further comprises a sweetener, a humectant, a mineral salt, a buffering component, a flavoring agent, a preservative, or a combination thereof.
[0145] 12. The composition according to any one of clauses 1 to 11, wherein the composition further comprises aloe vera, folic acid, hyaluronic acid, octylpyranoside, N-acetyl-D-glucosamine, N-acetyl-D-galactosamine, D-glucosamine hydrochloride, D-glucosamine sulfate, D-glucosamine, N-methyl-D-glucosamine, N-ethyl-D-glucosamine, N-octyl-D-glucosamine, xylitol, sorbitol, erythritol, mannitol, glycine, nonanoic acid, ethyl caprylate, DMSO, ceramide, arginine, betaine or oxyglycerol, vitamin E, vitamin B12, EDTA, cetylpyridinium chloride, chlorhexidine, other antibacterial agents or combinations thereof.
[0146] 13. The composition according to any one of clauses 1 to 12, wherein the composition comprises 1% to 20% by weight of a sweetener based on the total weight of the composition.
[0147] 14. The composition according to any one of Clauses 1 to 13, wherein the composition comprises 2.5% to 40% by weight of a wetting agent based on the total weight of the composition.
[0148] 15. The composition according to any one of Clauses 1 to 14, wherein the composition does not contain any quaternary ammonium antimicrobial compound.
[0149] 16. The composition according to any one of clauses 1 to 15, wherein the composition has a viscosity that makes it suitable for use as a sprayable composition or for delivery as a sprayable composition.
[0150] 17. The composition according to any one of Clauses 1 to 16, wherein the composition does not contain any quaternary ammonium compound.
[0151] 18. The composition according to any one of Clauses 1 to 17, wherein the composition can prevent, inhibit, disrupt, disperse, reduce, control the formation or maintenance of biofilms in areas in contact with the composition, or any combination thereof.
[0152] 19. The composition according to any one of Clauses 1 to 18, wherein the composition may affect hydration loss in the area in contact with the composition.
[0153] 20. The composition according to any one of clauses 1 to 19, wherein the composition may affect the lubricity or lubricity of the area in contact with the composition.
[0154] 21. A method for preventing, inhibiting, destroying, dispersing, reducing, or controlling the formation or maintenance of biofilms, or any combination thereof, in oral tissues, said method comprising: To bring oral tissues into contact with the composition according to any one of clauses 1 to 20.
[0155] 22. A method for influencing hydration loss in oral tissues, the method comprising: To bring oral tissues into contact with the composition according to any one of clauses 1 to 20.
[0156] 23. A method for affecting the lubrication capacity or lubricity of oral tissues, the method comprising: To bring oral tissues into contact with the composition according to any one of clauses 1 to 20.
[0157] 24. A method for influencing dry mouth, dry throat, or both, the method comprising: To bring oral tissues into contact with the composition according to any one of clauses 1 to 20.
[0158] Therefore, embodiments of the oral composition and method of use are disclosed. The above and other embodiments are all within the scope of the following claims. Those skilled in the art will recognize that this disclosure can be implemented in ways other than those disclosed. The disclosed embodiments are for illustrative purposes only and are not intended to be limiting.
Claims
1. A composition comprising: Based on the total weight of the composition, 0.1% to 4% by weight of one or more compounds of formula (I), HOCH2-(CHOH) n -CH2NR 1 R 2 (I) in: R 1 It is hydrogen or a C1 to C4 alkyl group; R 2 It is C(O)R 3 ; R 3 It is a straight-chain C8 to C10 alkyl group; and n is an integer from 2 to 5; One or more vegetable oils, based on the total weight of the composition, comprising 80% to 85% by weight. and The aqueous phase comprises: Water present in an amount of 14% to 16% by weight based on the total weight of the composition; Dipotassium hydrogen phosphate; Potassium dihydrogen phosphate; and Calcium hydrogen phosphate; The amount of the aqueous phase present is no more than 30% by weight based on the total weight of the composition; and One or more nonionic aromatic phenolic preservatives are present in an amount of 0.01% to 1% by weight based on the total weight of the composition; The composition thereon: It has a pH range of 4.5 to 9.5; It is a water-in-oil emulsion; It does not contain quaternary ammonium antimicrobial compounds; and It is edible.
2. The composition according to claim 1, wherein n is 4.
3. The composition according to claim 1, wherein, based on the total weight of the composition, dipotassium hydrogen phosphate is present in an amount of 0.155% by weight, potassium dihydrogen phosphate is present in an amount of 0.076% by weight, and calcium hydrogen phosphate is present in an amount of 0.0002% by weight.
4. The composition according to claim 1, wherein the one or more vegetable oils are selected from: sunflower oil, safflower oil, olive oil, coconut oil, palm oil, peanut oil, soybean oil, flaxseed oil, rapeseed oil, linseed oil, hemp seed oil, cocoa butter, walnut oil, corn oil, grapeseed oil, sesame oil, peanut oil, wheat germ oil, cottonseed oil, watermelon seed oil, lemon oil, orange oil, thistle oil, tomato seed oil, almond oil, perilla oil, low erucic acid rapeseed oil, pistachio fruit oil, hazelnut oil, camellia seed oil, shea butter, apricot kernel oil, oleic acid, and avocado oil.
5. The composition according to claim 1, wherein the one or more vegetable oils comprise corn oil.
6. The composition according to claim 1, wherein the one or more nonionic aromatic phenolic preservatives are present in an amount not exceeding 0.6% by weight based on the total weight of the composition.
7. The composition according to any one of claims 1 to 6, wherein the composition comprises a preservative mixture, the preservative mixture comprising: 77%-86% benzyl alcohol; 8%-15% salicylic acid; 3%-5% glycerin; and 1%-4% sorbic acid, Each content is based on the total weight of the preservative mixture.
8. The composition according to any one of claims 1 to 7, wherein one or more compounds of formula (I) comprise N-methyl-N-nonanoyl-D-glucosamine.
9. The composition according to any one of claims 1 to 8, wherein the composition is a crude emulsion.
10. The composition according to any one of claims 1 to 9, wherein the water is dispersed as water droplets in a continuous oil phase.
11. The composition according to any one of claims 1 to 10, wherein the composition reduces hydration loss of oral tissues in contact with the composition.
12. The composition according to any one of claims 1 to 11, wherein the composition increases the lubrication ability of oral tissues in contact with the composition.
13. The composition according to any one of claims 1 to 12, wherein the composition prevents, inhibits, disrupts, disperses, reduces or controls the formation or maintenance of biofilms on oral surfaces in contact with the composition.
14. The composition according to any one of claims 1 to 13, wherein: The one or more vegetable oils include corn oil, present in an amount of 82.47% by weight; Water is present in an amount of 14% by weight; One or more compounds of formula (I) contain N-methyl-N-nonanoyl-D-glucosamine, present in an amount of 0.7% by weight; Each content is based on the total weight of the composition.
15. The composition of claim 1, wherein the composition comprises: Corn oil present in an amount of 82.47% by weight based on the total weight of the composition; Water is present in an amount of 14% by weight based on the total weight of the composition; N-methyl-N-nonanoyl-D-glucosamine is present in an amount of 0.7% by weight based on the total weight of the composition; N-methyl-D-glucosamine; Xylitol; Sucralose; Spearmint flavoring agent; Dipotassium hydrogen phosphate; Potassium dihydrogen phosphate; dicalcium phosphate; and A mixture of preservatives containing benzyl alcohol, salicylic acid, glycerin and sorbic acid.