Intake oral care compositions and uses thereof

Abstract

The present disclosure relates to ingestible oral care compositions and their use, for example, to control plaque and / or gingival inflammation in a subject. For example, ingestible oral care compositions may comprise proteins, lipids, polysaccharides and / or derivatives thereof, and optionally active ingredients in a water-based orally acceptable carrier.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This disclosure claims the benefit of priority to co-pending U.S. Provisional Application No. 63 / 436,529, filed December 31, 2022, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] The present disclosure relates to ingestible oral care compositions and their use, for example, for controlling dental plaque and / or gum inflammation in a subject. Background Art

[0004] Dental plaque is a sticky, bacterial-containing film that coats teeth. It is associated with common dental diseases, particularly caries and gum disease. Recent studies have also shown that dental plaque infection may lead to systemic inflammation. Dental plaque is a biofilm composed of microorganisms distributed within an intercellular matrix. This matrix is ​​primarily composed of the following organic and inorganic components: polysaccharides, proteins, glycoproteins, and lipids; and calcium, phosphorus, sodium, potassium, and fluoride. Bacterial exopolysaccharides account for 50–95% of the dry weight of the plaque biofilm. These components contribute to the structural integrity of the biofilm and its attachment to the tooth surface.

[0005] Gingivitis affects approximately 50% of adults worldwide. Gingivitis and periodontitis are the same persistent inflammatory disease, and not all patients with gingivitis will develop periodontitis. Gingivitis management is both a primary prevention strategy for periodontitis and a secondary prevention strategy for recurrent periodontitis. The most important risk factor for gingivitis and periodontitis is the accumulation of bacterial plaque biofilms at and below the gingival margin, where dysbiosis occurs and is associated with an inappropriate and destructive host inflammatory immune response. Therefore, oral care products that can be applied topically to gingival tissue to control gingival inflammation, prevent gingivitis, and / or prevent the progression of gingivitis to periodontitis would be ideal for managing gum disease.

[0006] Daily brushing, flossing, and the use of antimicrobial mouth rinses are commonly recommended measures to control plaque accumulation. While these measures can provide temporary removal and / or control of biofilm, they cannot completely eliminate it. Furthermore, if mechanical interventions are not properly controlled, frequent mechanical interventions can adversely affect the soft tissues surrounding the teeth and lead to gingival recession, particularly in the elderly. Although plaque can be controlled with these measures, the dynamic interactions between the host and microbiome communities, modern diet, and / or stressors necessitate the need for non-invasive adjuncts to help relieve mechanically affected soft tissues, maintain oral microbial homeostasis, and prevent biofilm-induced pathogenicity and / or inflammation. Oral care products that are safe and convenient for daily use and that provide longer-lasting and more effective protection of the gums and teeth from biofilm proliferation and dysbiosis would complement current oral care regimens, improve oral health maintenance, and potentially enhance systemic health related to oral health. However, the moist environment and dynamic functions of the oral cavity pose significant challenges for leave-in oral care products. Another challenge with ingestible oral care products is the potential for plaque regrowth (see, for example, Rubido et al., In vivo antiplaque effect of three edible toothpastes Med Oral Patol Oral Cir Bucal. 2014 Jan 1; 19(1): e88-92). SUMMARY OF THE INVENTION

[0008] Briefly, the present disclosure includes methods and compositions for application to tooth and gum surfaces that persist on the contact surface for an extended period of time after application and are safely ingested. Surprisingly, the highly biocompatible, ingestible oral compositions of the present disclosure control plaque regeneration and accumulation in a non-invasive manner without the need for mechanical forces or antimicrobial chemicals.

[0009] When applied to a tooth surface, the exemplary ingestible oral care compositions of the present disclosure adhere to existing biofilms, altering the cohesiveness of the EPM and reducing the mechanical stability of the matrix while acting as a physical barrier to prevent further bacterial attachment to the existing biofilm. While not wishing to be bound by theory, this highly biocompatible composite appears to act like a camouflage for oral biofilms, thereby disrupting existing biofilms and interfering with their growth, weakening biofilm growth, and maintaining the biofilm at a level compatible with oral health.

[0010] The present disclosure includes ingestible oral care compositions comprising a protein, a lipid, a polysaccharide and / or derivatives thereof and, optionally, an active ingredient in an aqueous-based orally acceptable vehicle.

[0011] In embodiments, the ingestible oral care composition further comprises a pH neutralizer.In embodiments, the ingestible oral care composition comprises an active ingredient.

[0012] The present disclosure also includes the use of the ingestible oral care compositions described herein to control gingival inflammation in a subject. The present disclosure also includes the use of the ingestible oral care compositions described herein comprising active ingredients to control respiratory diseases in a subject through the mouth and throat. The present disclosure also includes the use of the ingestible oral care compositions described herein to prevent systemic diseases associated with periodontitis in a subject. The present disclosure also includes the use of the ingestible oral care compositions described herein to destroy plaque on the oral surface of a subject in a non-invasive manner, prevent plaque regeneration and / or reduce plaque. The present disclosure also includes the use of the ingestible oral care compositions described herein comprising active ingredients to deliver the active ingredient to a subject in need thereof.

[0013] Certain embodiments of the present disclosure include, but are not limited to: a) applying the product to the entire tooth and gum surface using a soft-bristled toothbrush and allowing it to slowly disperse into the oral cavity, preferably after regular nighttime cleaning with toothpaste and floss, wherein the oral care product serves as a leave-on conditioner after cleaning the teeth and acts as a simple and convenient supplement to the existing oral care regimen; b) manually applying or smearing the product to specific target tooth and gum surfaces, i.e., areas with dental problems, including pain, bleeding, sensitivity, swelling, gum inflammation, gum recession, etc., with or without the aid of flossing, if necessary, pushing the product further into the tooth root or periodontal pocket for optimal results; c) manually applying the product with a brush or with the aid of flossing, or with a specialized dental product application tool, such as a curve tipped syringe for therapeutic purposes. The product can be applied directly to a target site on the tooth and gum surface, or to the root of a specific tooth or to a specific periodontal pocket, as a medication, using a syringe. In this application, the product carries a therapeutic agent suitable for local application. d) The product can include a health-promoting ingredient or drug that provides additional benefits to systemic health, or specifically respiratory health, through regular use of the product, achieved through extended release and uptake after application. This prolonged contact with the tooth and gum surface allows for a longer local delivery time, creating the opportunity for more effective delivery of the health-promoting ingredient or drug and a safer, long-term profile.

[0014] Exemplary oral care products suitable for the above method can include, but are not limited to, a matrix (base) of the following materials in an orally acceptable carrier: polysaccharides and polysaccharide derivatives, proteins, lipids, and the carrier includes humectants, sweeteners, flavorings, buffers, water and / or preservatives. Only the matrix can be applied to inhibit plaque aggregation and prevent dental caries and periodontal disease. In another embodiment, the ingestible oral care composition further includes one or more pH neutralizers, such as inorganic salts, and the pH neutralizer can, for example, neutralize the acid in situ and / or further prevent dental caries. In another embodiment, the oral composition further includes one or more active ingredients that promote oral health, including but not limited to antioxidants, anti-inflammatory agents, antimicrobial agents, nutrients, sensory agents (sensory agent), plant extracts, essential oils, etc., for managing local pain, sensitivity, gingival inflammation, gingival swelling, bleeding, gingival recession, malodor, etc., or potentially controlling systemic or respiratory health problems. In another embodiment, as a safe and effective treatment option for gingival disease, the oral composition carries a pharmaceutical active ingredient in the matrix for targeted local delivery to tooth roots and / or periodontal pockets.

[0015] According to the following detailed description, other features and advantages of the present disclosure will become apparent. However, it should be understood that the detailed description and specific examples, although indicating embodiments of the present disclosure, are given only as examples, and the scope of the claims should not be limited by these embodiments, but should be given the broadest interpretation consistent with the overall description.

[0016] BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 Graph showing stained bacterial counts of samples collected from the oral cavity of subjects applying an ingestible oral care composition according to an embodiment of the present disclosure (left column) compared to a control (right column), with samples collected at 0, 15, 30, 60, 90, and 120 minutes from left to right. Detailed Description of the Invention

[0019] I. Definition

[0020] Unless otherwise indicated, the definitions and embodiments described in this section and elsewhere are intended to apply to all embodiments and aspects of the disclosure as deemed applicable by one skilled in the art.

[0021] As used herein, the words “comprising” (and any form of “comprising,” such as “comprise” and “comprises”), “having” (and any form of “having,” such as “have” and “has”), “including” (and any form of “including,” such as “include” and “includes”), or “containing” (and any form of “containing”). Any form, such as "contain" and "contains," is inclusive or open-ended and does not exclude additional unlisted elements or process / method steps. As used herein, the phrase "consisting of" and its derivatives are intended to be closed terms that specify the presence of the recited features, elements, components, groups, integers, and / or steps and exclude the presence of other unrecited features, elements, components, groups, integers, and / or steps. As used herein, the term "consisting essentially of" is intended to specify the presence of the recited features, elements, components, groups, integers, and / or steps, as well as those features, elements, components, groups, integers, and / or steps that do not materially affect the basic and novel characteristics of the features, elements, components, groups, integers, and / or steps.

[0022] As used herein, terms of degree such as "substantially", "about" and "approximately" refer to a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree should be construed to include a deviation of at least ±5% of the modified term as long as such deviation does not negate the meaning of the modified term.

[0023] This disclosure therefore includes plural referents in the singular forms "a," "an," and "the," unless the context clearly dictates otherwise.

[0024] As used herein, the term "and / or" means that the listed items are present or used alone or in combination. In practice, the term means that "at least one" or "one or more" of the listed items are used or present.

[0025] By "ingestible" is meant, for example, that the ingredients of the product / composition, especially the ingredients in the matrix, are considered suitable for consumption by the subject at the levels used in the present product / composition, for example, they can be "generally recognized as safe" (GRAS) materials and / or food grade as determined by the United States Food and Drug Administration (FDA), and the additional active ingredients can be, for example, GRAS materials, food grade materials and / or used in other forms at levels suitable for daily oral consumption. It will be appreciated by those skilled in the art that in embodiments where the active ingredient comprises a pharmaceutically active compound, the active ingredient is ideally present in a form that is, for example, compatible with the treatment delivered by the subject via an ingestible oral care composition, and is administered / used to the subject in an amount effective to achieve the desired effect, at a dosage and time necessary to achieve the desired effect. Therefore, according to an embodiment, the product / ingestible oral care composition of the present disclosure is suitable for retention in the oral cavity, for example, after daily application or multiple applications in a day, or retained in the oral cavity as prescribed. The ingestible oral care compositions of the present disclosure can thus act for a long time on the surface of teeth and gums, for example as leave-on oral care products, to destroy plaque, prevent plaque regeneration, and / or reduce plaque in a non-invasive manner. Alternatively, in some embodiments, the ingestible oral care formulations are used for temporary therapeutic purposes.

[0026] As used herein, the term "non-invasive" and the like refers to, for example, applying an antimicrobial chemical without applying significant mechanical force.

[0027] "Prolonged time" means that after the product is applied to the tooth and gum surfaces, the product remains on these surfaces for 10 minutes or more. The length of the residence time is affected by oral activity after application. In an embodiment, a longer residence time is achieved by applying the product to the entire tooth and gum surfaces using a soft-bristled brush after cleaning the teeth with toothpaste and / or flossing before going to bed at night.

[0028] "Pleasant taste and convenient application method" means that the consistency and texture of the product are semi-solid, similar to commercial toothpaste. The product can be packaged in a manner similar to toothpaste, or in a different manner. The product can also be applied to the gums and tooth surfaces with a toothbrush, preferably with a soft-bristled toothbrush, with gentle movements to cover all surface areas. Products applied in this manner are essentially gels that subsequently dissolve and disperse into the oral cavity, leaving no solid residue in the oral cavity over time, but preferably leaving a pleasant and refreshing taste embedded in the product. Products applied in this manner can be easily added to the current daily oral care routine after cleaning with toothpaste and flossing, as a supplementary leave-on product in the teeth and gum conditioning step, which utilizes the functional oral care active ingredients in a safer and more effective manner than when used in toothpaste or mouthwash (where the above active ingredients only have a brief contact time before being spit out or rinsed out of the mouth).

[0029] As used herein, the term "oral surface" refers to any surface within the oral cavity suitable for application of an ingestible oral care composition, such as suitable mucosal surfaces (e.g., gums), natural teeth, artificial teeth (e.g., implants), and teeth with dental restorations (e.g., crowns or bridges), and combinations thereof.

[0030] II. Ingestible Oral Care Compositions and Uses Thereof

[0031] The present disclosure includes oral care products comprising a matrix consisting of: polysaccharides and / or polysaccharide derivatives, proteins, lipids in an orally acceptable carrier, the carrier including a humectant, a sweetener, a flavoring, a buffer, water, and / or a preservative. In the oral care products, carefully selected polysaccharides and / or polysaccharide derivatives, proteins, and lipids, as well as optional inorganic salts (which are either part of the natural biofilm composition or a specific substitute with high biocompatibility), are combined with, for example, humectants, sweeteners, flavorings, and water to prepare the products, which are also able to adhere to the surfaces of teeth and gums, but in terms of consistency and texture, can be easily applied to the local surface and stay there for a certain period of time before being fully dispersed into the oral cavity. Once the products are applied to the local surface after the teeth cleaning procedure, the retention of the products on the local surface will destroy the residual plaque, form a physical barrier to delay the formation of biofilm that would otherwise recur on the tooth surface, and further reduce the chance of plaque formation and aggregation on the tooth surface. Optionally, the product includes inorganic salts to neutralize the acid in situ, which also prevent caries and reduce gum inflammation and associated local bleeding and / or swelling. Optionally, an active ingredient is included to be delivered topically.

[0032] The present disclosure also includes an ingestible oral care composition comprising: a polysaccharide and / or its derivatives, a protein, a lipid, an inorganic salt pH neutralizer, a humectant, a sweetener, a flavor, water, and optionally an active ingredient. The present disclosure also includes an ingestible oral care composition comprising: a protein, a lipid, a polysaccharide and / or its derivatives, water, and optionally an inorganic salt pH neutralizer, a humectant, a sweetener, a flavor, and / or an active ingredient.

[0033] The present disclosure also encompasses ingestible oral care compositions comprising a protein, a lipid, a polysaccharide and / or derivatives thereof and, optionally, an active ingredient in an aqueous-based orally acceptable carrier.

[0034] The protein can be any suitable protein or combination thereof and is present in any suitable amount. In an embodiment, the amount of protein present is from about 0.05 wt % to about 10 wt % based on the total weight of the ingestible oral care composition. In another embodiment, the amount of protein present is from about 0.1 wt % to about 5 wt % based on the total weight of the ingestible oral care composition. The proteins in the above-mentioned products include, but are not limited to, collagen, gelatin, soy protein, pea protein, and particularly proline-rich proteins to adhere to the tooth surface. Therefore, those skilled in the art will readily recognize that the term "protein" as used herein also includes suitable substances derived from proteins, such as, but not limited to, gelatin and / or hydrolyzed collagen, and substances comprising suitable mixtures of proteins, such as, but not limited to, soy protein, pea protein, rice protein, and / or whey protein. In an embodiment, the protein is a proline-rich protein. In an embodiment, the protein is gelatin, hydrolyzed collagen, pea protein, soy protein, rice protein, whey protein, or a combination thereof. In another embodiment, the protein is selected from collagen, gelatin, soy protein, pea protein, and a combination thereof. In an embodiment, the protein is a combination of hydrolyzed collagen and gelatin. Gelatin is preferably selected due to its high biocompatibility and its potential to prevent gum recession and promote gum healing, regeneration, and attachment to teeth. In an embodiment, the protein is gelatin. In another embodiment, the gelatin is present in an amount of 0.1 wt% to about 5 wt% based on the total weight of the ingestible oral care composition.

[0035] The polysaccharide and / or its derivative can be any suitable polysaccharide, polysaccharide derivative or combination thereof, and is present in any suitable amount. In an embodiment, the amount of the polysaccharide and / or its derivative present is from about 0.3 wt % to about 42 wt % based on the total weight of the ingestible oral care composition. In an embodiment, the amount of the polysaccharide and / or its derivative present is from about 1.6 wt % to about 27 wt % based on the total weight of the ingestible oral care composition. The polysaccharide and / or polysaccharide derivative in the above-mentioned product includes, but is not limited to, plant-based materials such as cellulose and cellulose derivatives, pectin, acacia gum, gum arabic, inulin, guar gum, tara gum and locust bean gum; animal-based materials such as hyaluronic acid, sodium hyaluronate, chitin, chitosan and heparin; microbial-based materials such as pullulan, xanthan gum, gellan gum and succinoglycan; and algae-based materials such as alginate, agar, carrageenan, fucoidan, etc. In embodiments, polysaccharide and / or its derivatives are selected from plant-based materials, animal-based materials, microorganism-based materials, algae-based materials and combinations thereof. In another embodiment, polysaccharide and / or its derivatives are selected from cellulose, cellulose derivatives, pectin, acacia gum, gum containing arabic galactan, gum arabic, inulin, guar gum, tara gum, locust bean gum, hyaluronic acid, sodium hyaluronate, chitin, chitosan, heparin, pullulan, xanthan gum, gellan gum, succinoglycan, alginic acid (algin), alginate, agar, carrageenan, fucoidan and combinations thereof. Select or combine one or more of the above-mentioned materials to facilitate the above-mentioned characteristics, wherein one of preferred selections is a combination of pectin, gum arabic, guar gum, xanthan gum and alginate. Therefore, in embodiments, polysaccharide and / or its derivatives are a combination of gum arabic, pectin, guar gum, xanthan gum and sodium alginate. In another embodiment, polysaccharide and / or its derivatives are a combination of gum containing arabic galactan, guar gum, xanthan gum and sodium alginate. The gum containing arabinogalactan is any suitable gum containing arabinogalactan or a combination thereof. In an embodiment, the gum containing arabinogalactan is larch arabinogalactan, gum ghatti, gum arabic or a combination thereof. In another embodiment, the polysaccharide and / or its derivative is a combination of gum arabic, guar gum, xanthan gum and sodium alginate. In an embodiment, based on the total weight of the ingestible oral care composition, the amount of gum containing arabinogalactan present is from about 0.1 wt% to about 30 wt%; the amount of guar gum present is from about 0.05 wt% to about 1 wt%; the amount of xanthan gum present is from about 0.05 wt% to about 1 wt%; and the amount of sodium alginate present is from about 0.1 wt% to about 10 wt%.In an embodiment, the arabinogalactan-containing gum is gum arabic and is present in an amount from about 1 wt% to about 20 wt%; guar gum is present in an amount from about 0.05 wt% to about 0.5 wt%; xanthan gum is present in an amount from about 0.05 wt% to about 0.5 wt%; and sodium alginate is present in an amount from about 0.5 wt% to about 6 wt%, based on the total weight of the ingestible oral care composition.

[0036] Lipid is any suitable lipid or its combination, and exists in any suitable amount.In an embodiment, based on the gross weight of the oral care composition that can be taken in, the amount of the lipid present is about 0.2wt% to about 27wt%.In another embodiment, based on the gross weight of the oral care composition that can be taken in, the amount of the lipid present is about 1wt% to about 10wt%.The lipid in the above-mentioned product includes but is not limited to medium-chain triglycerides, grape seed oil, linseed oil, avocado oil, coconut oil, sunflower oil, olive oil, sesame oil etc.Lipid can provide antioxidant and / or anti-inflammatory effect.One of preferred selections is caprylic / capric triglyceride.Therefore, those skilled in the art will easily understand that term " lipid " as used herein also includes the suitable combination of lipid and the suitable material derived and / or prepared by lipid, such as but not limited to caprylic / capric triglyceride.In an embodiment, lipid is medium-chain triglyceride, grape seed oil, linseed oil, avocado oil, coconut oil, palm oil, sunflower oil, olive oil, sesame oil or its combination.In another embodiment, lipid is caprylic / capric triglyceride. In another embodiment, the caprylic / capric triglyceride is present in an amount from about 1 wt% to about 10 wt%, based on the total weight of the ingestible oral care composition.

[0037] In embodiments, the ingestible oral care composition further comprises a pH neutralizer. In embodiments, the pH neutralizer is an inorganic salt pH neutralizer. Inorganic salts are any suitable inorganic salts or combinations thereof that can act as pH neutralizers in ingestible oral care compositions, and are present in any applicable amount. For example, in the ingestible oral care compositions of the present disclosure, pH neutralizers are advantageously able to neutralize in situ acid over a long period of time, thereby, for example, preventing dental caries (caries) and / or dental caries. In embodiments, based on the gross weight of the ingestible oral care compositions, the amount of the pH neutralizer present is from about 0.2wt% to about 3wt%. The inorganic salts in the above-mentioned products include, but are not limited to, dibasic calcium phosphate dihydrate, anhydrous dibasic calcium phosphate, and tricalcium phosphate. Therefore, in embodiments, the pH neutralizer is anhydrous dibasic calcium phosphate dihydrate, dibasic calcium phosphate dihydrate, tricalcium phosphate, or combinations thereof. The inorganic salts are fine powders that are not abrasive and have limited solubility in water. Once applied, the salt powder embedded in the product remains on the surface of the teeth and gums, continuously neutralizing local acids and maintaining a neutral pH level, thereby preventing tooth surface erosion and caries, inhibiting plaque accumulation, and preventing gum disease. The above salts, when combined in specific ratios, can also provide a pH adjustment function for the overall pH of the above product, keeping it between 6.5 and 7.5. One preferred option is a combination of anhydrous calcium hydrogen phosphate and tricalcium phosphate of fine particle size. Therefore, in an embodiment, the ingestible oral care composition comprises a combination of anhydrous calcium hydrogen phosphate and tricalcium phosphate.

[0038] Those skilled in the art will recognize that, in addition to water, the water-based orally acceptable carrier may also contain one or more ingredients selected from, for example, a buffer, a humectant, a sweetener, a flavoring, and a preservative. The water-based orally acceptable carrier may be present in any suitable amount to obtain the desired product, and the determination of the amount may be performed by those skilled in the art. For example, those skilled in the art will recognize that the ingestible oral care compositions of the present disclosure are not in the form of a film, but rather in a semisolid form, such as a gel.

[0039] The buffer is any suitable buffer or combination thereof and is present in any suitable amount. In an embodiment, the buffer is trisodium phosphate, sodium citrate, citric acid and sodium hydroxide or a combination thereof. In another embodiment, the buffer is a combination of sodium citrate, citric acid and sodium hydroxide. Unlike pH neutralizers used to have a neutralizing effect when applied to the oral surface of a subject, the buffer and the amount thereof are selected to have an effect on the product / ingestible oral care composition of the present disclosure. In an embodiment, the amount of the buffer present is from about 0.1 wt% to about 1 wt% based on the total weight of the ingestible oral care composition.

[0040] Wetting agent is any suitable wetting agent or its combination, and is present in any suitable amount. The wetting agent in the above-mentioned product includes but is not limited to glycerol, propylene glycol, butylene glycol, propanediol, pentanediol and other organic wetting agents, such as aloe vera. Wetting agent keeps the moisture in the above-mentioned product, helps to form a semi-solid structure, and prevents microorganisms from growing in the above-mentioned product. One of preferred selections is the combination of glycerol and aloe vera, because aloe vera has soothing properties. Therefore, in an embodiment, wetting agent is a combination of glycerol and aloe vera. In another embodiment, wetting agent comprises glycerol, is mainly composed of it or is composed of it. In another embodiment, wetting agent comprises glycerol.

[0041] Sweetener is any suitable sweetener or its combination, and is present in any suitable amount.The sweetener in the above-mentioned product includes but is not limited to sugar alcohol, such as xylitol, erythritol, sorbitol, wherein low / zero calorie sweetener, such as erythritol and xylitol, is preferred because of its widely recognized benefit used in oral care products;And other sugar substitutes, such as pure stevia, monk fruit extract, acesulfame potassium, Advantame (Advantame), aspartame (Aspartame), neotame, saccharin and sucralose.In an embodiment, sweetener is selected from sugar alcohol, other sugar substitutes and combinations thereof.In another embodiment, sweetener is selected from xylitol, erythritol, sorbitol, pure stevia, monk fruit extract, acesulfame potassium, Advantame, aspartame, neotame, saccharin and sucralose.The combination of erythritol and / or erythritol and xylitol is a preferred selection for this product. In an embodiment, the sweetener is erythritol and / or a combination of erythritol and xylitol. In another embodiment, the sweetener comprises xylitol, consists essentially of xylitol, or consists of xylitol. In a further embodiment, the sweetener comprises xylitol.

[0042] The flavoring agent is any suitable flavoring agent or combination thereof and is present in any suitable amount. The flavoring agent in the above-mentioned product includes, but is not limited to, peppermint and spearmint. Preferred flavoring agents are mint flavoring agents, including one or both of peppermint and / or spearmint. Thus, in one embodiment, the flavoring agent is mint flavoring agent. In another embodiment, the flavoring agent is peppermint, spearmint, or a combination thereof.

[0043] Wherein, the ingredients in the above-mentioned products, when appropriately combined with water, not only provide the above-mentioned properties to the matrix, but also provide a tooth-friendly microbiome environment when used, support the diversity of the microbiome in the oral cavity, and inhibit the excessive growth of acid-producing and / or pathogenic microorganisms. In an embodiment, the above-mentioned preferred appropriate combination of each component includes a specific proportion of each component, an order of addition, and specific mixing conditions and temperatures, wherein, when optimized, the above-mentioned physical and chemical properties can be achieved. However, it should be recognized by those skilled in the art that the product / composition can be prepared using methods common in the field of oral products, and a suitable method can be easily selected.

[0044] In some embodiments, the product / composition includes an active ingredient. Therefore, the active ingredient can be delivered to the oral cavity by the ingestible oral care composition of the present disclosure. The active ingredient is any suitable active ingredient or its combination, and is present in any suitable amount, for example, this may depend on the identity of the active ingredient or its combination. The active ingredient with specific health-promoting functions and physical and chemical properties (such as pH, solubility and stability) compatible with the matrix can be embedded in a manner well known to those skilled in the art. The above-mentioned active ingredient can be advantageously used in relatively low concentrations, but because it plays a local function in situ on the gums and gum surface targets to reduce plaque, control gingivitis, prevent periodontitis and prevent caries for a long time, it is possible to produce higher efficacy and better long-term safety. The above-mentioned active ingredient includes but is not limited to antioxidants, anti-inflammatory agents, antimicrobials, nutrients (such as vitamins), sensory agents (sensoryagent), plant extracts, essential oils, etc. In another embodiment, the active ingredient is selected from antioxidants, anti-inflammatory agents, antimicrobials, nutrients (such as vitamins), sensory agents, plant extracts, essential oils and combinations thereof. In another embodiment, the active ingredient comprises vitamins. The vitamin can be any suitable vitamin or combination thereof. In another embodiment, the vitamin is a combination of vitamin C and vitamin B12. In another embodiment, the amount of vitamin C present is from about 0.1 wt% to about 2 wt%, and the amount of vitamin B12 present is from about 0.001 wt% to about 0.05 wt%. In another embodiment, the active ingredient comprises a plant extract. The plant extract can be any plant extract suitable for use in an ingestible oral care composition or a combination thereof. In another embodiment, the active ingredient comprises an essential oil. The essential oil can be any essential oil suitable for use in an ingestible oral care composition or a combination thereof.

[0045] Among them, the product with the above-mentioned active ingredient can be applied to the tooth cleaning program as a whole conditioning supplement as described above. If necessary, with or without the help of dental floss, the product can be further pushed into the tooth root and / or periodontal pocket, and it can also be applied to a specific part of the tooth and / or gum surface alone or together with other oral procedures to alleviate certain tooth and / or gum problems, such as gum swelling, pain, bleeding, sensitivity, malodor, periodontitis, etc. In some embodiments, an oral care product / composition is provided that is safe to ingest and suitable for long-term daily use in the oral cavity, has a pleasant mouthfeel and a convenient application method. Unlike toothpaste and oral rinses, which need to be spit out or rinsed away afterwards, this product is designed to be left on the tooth and gum surface in the oral cavity after application. The product slowly disperses into the local environment, thereby giving its ingredients a long time window to act locally on the tooth and gum surface. The product is not intended for cleaning purposes, but rather provides improved maintenance and protection by extending its local presence in the oral cavity (particularly on and / or around the teeth and gums) to prevent caries and reduce periodontal disease. The product may comprise a semi-solid matrix and impart specific functions locally on and / or around the teeth and gums after ingestion, as well as systemic benefits or benefits to the respiratory system.

[0046] The present invention is also characterized in that, with or without the assistance of a curved dental syringe or other fine-pointed dental tool, the above-mentioned matrix is ​​used as a drug delivery vehicle to specifically deliver the pharmaceutical active ingredient to the periodontal pocket and surrounding area. Therefore, in an embodiment, the active ingredient comprises a pharmaceutically active compound. In another embodiment, the active ingredient comprises a pharmaceutically active compound, a vitamin, a plant extract, an essential oil, or a combination thereof. In a further embodiment, the active ingredient comprises a pharmaceutically active compound, and optionally vitamins, plant extracts, essential oils, or a combination thereof. Due to the high biocompatibility of the matrix, the above-mentioned drug delivery system can also be applied to similar target areas, such as implants, teeth with crowns or bridges, or other natural teeth, or artificial teeth that control pain and inflammation after surgery and minimize side effects. The above-mentioned pharmaceutically active ingredient is preferably compatible with the matrix in terms of physical and chemical properties (including but not limited to pH, solubility, and stability). In another feature included in the present invention, the above-mentioned product comprises a matrix material and a functional active ingredient that promotes microbial balance and / or overall health (not only for the oral cavity, but also for the respiratory system and / or systemic system) when used regularly. Examples of the aforementioned base materials include, but are not limited to, prebiotics, such as pectin and / or inulin; examples of the aforementioned active ingredients include, but are not limited to, plant extracts, such as green tea extract and / or licorice extract.

[0047] The present disclosure also includes the use of the ingestible oral care compositions described herein to control gingival inflammation in a subject. The present disclosure also includes the use of the ingestible oral care compositions described herein to prepare a medicament for controlling gingival inflammation in a subject. The present disclosure also includes the ingestible oral care compositions described herein for controlling gingival inflammation in a subject. The present disclosure also includes a method of controlling gingival inflammation in a subject, the method comprising applying the ingestible oral care compositions described herein to an oral surface of the subject. In embodiments, the oral surface includes a gingival surface or a portion thereof.

[0048] The present disclosure also includes the use of an ingestible oral care composition comprising an active ingredient as described herein to control a respiratory disease of a subject through the mouth and throat. The present disclosure also includes the use of an ingestible oral care composition comprising an active ingredient as described herein to prepare a medicament for controlling a respiratory disease of a subject through the mouth and throat. The present disclosure also includes the ingestible oral care composition comprising an active ingredient as described herein for controlling a respiratory disease of a subject through the mouth and throat. The present disclosure also includes a method of controlling a respiratory disease of a subject through the mouth and throat in need thereof, the method comprising applying an ingestible oral care composition comprising an active ingredient as described herein to the oral surface of a subject.

[0049] The present disclosure also includes the use of the ingestible oral care compositions described herein for preventing systemic diseases associated with periodontitis in a subject. The present disclosure also includes the use of the ingestible oral care compositions described herein for preparing a medicament for preventing systemic diseases associated with periodontitis in a subject. The present disclosure also includes the ingestible oral care compositions described herein for preventing systemic diseases associated with periodontitis in a subject. The present disclosure also includes a method for preventing systemic diseases associated with periodontitis, comprising applying the ingestible oral care compositions described herein to an oral surface of a subject.

[0050] The present disclosure also includes the use of the ingestible oral care compositions described herein for non-invasively destroying plaque on the oral surfaces of a subject, preventing plaque regeneration, and / or reducing plaque. The present disclosure also includes the ingestible oral care compositions described herein for non-invasively destroying plaque on the oral surfaces of a subject, preventing plaque regeneration, and / or reducing plaque. The present disclosure also includes a method for non-invasively disrupting plaque on the oral surfaces of a subject, preventing plaque regeneration, and / or reducing plaque, comprising applying the ingestible oral care compositions described herein to the oral surfaces of a subject.

[0051] The present disclosure also includes the use of an ingestible oral care composition comprising an active ingredient as described herein to deliver an active ingredient to a subject in need thereof. The present disclosure also includes the use of an ingestible oral care composition comprising an active ingredient as described herein to prepare a medicament for delivering an active ingredient to a subject in need thereof. The present disclosure also includes an ingestible oral care composition comprising an active ingredient as described herein for delivering an active ingredient to a subject in need thereof. The present disclosure also includes a method for delivering an active ingredient to a subject in need thereof, the method comprising applying an ingestible oral care composition comprising an active ingredient as described herein to the oral surface of a subject.

[0052] In embodiments, the subject is a human.

[0053] The following are non-limiting examples of the present disclosure: Example

[0054] Example 1

[0055] The ingestible oral care compositions of the present invention can be prepared using methods common in the field of oral products. The ingredients of the exemplary oral care compositions are shown in Table 1. In an exemplary procedure for preparing the ingestible oral care compositions, gelatin and polysaccharides are first dispersed and hydrated in an orally acceptable carrier. Medium-chain triglycerides unexpectedly act as cross-linking agents between proteins and polysaccharides and increase the viscosity of the biopolymer composite matrix. Once the biopolymer composite matrix is ​​formed, the remaining ingredients, flavorings, and active ingredients to neutralize the pH are slowly introduced into the matrix to avoid trapping air. Buffers, sweeteners, flavorings, and humectants such as glycerol are introduced into water to form an orally acceptable carrier.

[0056] Table 1

[0057]

[0058]

[0059] Gelatin was included for its biocompatibility and potential as a proline-rich protein to promote adhesion to tooth surfaces. Initial examples were prepared using pectin, gum arabic, guar gum, xanthan gum, and sodium alginate. This polysaccharide mixture can be used to prepare the ingestible oral care composition of the present disclosure. However, differences in pectin sources and inconsistencies in the final mixture led to focus on four other natural gums.

[0060] The challenge in preparing ingestible oral care products is to achieve local retention of the product using ingestible ingredients. The gelatin and polysaccharide mixture shown in Table 1 exhibited adhesion to the tooth surface. However, its retention time was extremely short (less than 15 minutes). Surprisingly, when medium-chain triglycerides were added to the gelatin and polysaccharide matrix, the viscosity increased, the consistency of the matrix improved, and the retention on the tooth surface increased to nearly 30 minutes. However, it was also found that the amount of medium-chain triglycerides that could be fully incorporated into the gelatin and polysaccharide matrix was proportional to the other biopolymers. The gel matrix produced in the amounts listed in Table 1 can be used as an oral care product in a squeeze container, and similar proportions are expected to exhibit similar properties.

[0061] Another challenge with ingestible oral care products is plaque regeneration (see, for example, Rubido et al., Invivo antiplaque effect of three edible toothpastes Med Oral Patol Oral Cir Bucal. 2014 Jan 1; 19(1): e88-92). The effects of single gum solutions on β-glucan, a polysaccharide similar to that in EPS, were tested. Surprisingly, the amount (size) of β-glucan in gel form slowly decreased in the gum solution, with the rate decreasing in the following order: gum arabic > alginate > guar gum > xanthan gum. Therefore, other gums containing arabinogalactan, which are similar to gum arabic and have highly branched polysaccharides with L-arabinose side chains, were also tested. Larch arabogalactan and ghatti gum exhibited similar effects on β-glucan gels in solution as gum arabic.

[0062] A similar effect was observed with the initial reduction of the number of bacteria present after applying the products listed in Table 1 to the β-glucan gel. As β-glucan is a major component of biofilms, this suggests a potential interaction between the products and biofilm polysaccharides, which could, for example, lead to destabilization and degradation of the biofilm and further prevent plaque growth.

[0063] The product in Table 1 contains gelatin, caprylic / capric triglycerides, and a polysaccharide combination of sodium alginate, gum arabic, xanthan gum, and guar gum. The proteins, lipids, and polysaccharides in the EPM contribute to the biofilm as an energy source, structural component, and communication liaison. All of these molecules are involved in the attachment of bacteria to the biofilm and subsequent interactions within the biofilm. Unlike previous products that use polymers or polysaccharides as adhesive carriers for attachment to the tooth surface, the polysaccharide combination in this product is not adhesive enough and cannot attach to the tooth surface on its own. Although not wishing to be bound by theory, these polysaccharides, especially sodium alginate and gum arabic, appear to have an antagonistic effect on glucans, which are the main components of the EPM polysaccharides. Xanthan gum and guar gum are both advantageously used at minimal levels to promote the final viscoelastic properties of the product, rather than as viscosity enhancers. Gelatin, the most biocompatible protein, has different hydrophilic (anionic, cationic) and hydrophobic moieties on its amino acid chain, which interact with the lipids and polysaccharides that serve as the key structural backbone and help attach these components to the dental biofilm. Medium-chain triglycerides also interact with the gelatin and polysaccharide combination, surprisingly increasing the viscosity of the composite. Although not wishing to be bound by theory, this suggests that weak cross-linking with the composite is possible.

[0064] Example 2

[0065] Before collecting oral samples, subjects were asked to brush their teeth with ordinary toothpaste for 3 minutes. After brushing, subjects applied the oral care gel product of Table 1 to the tooth surface at the gum margin and used a soft-bristled toothbrush to make it even and enter the gingival sulcus as much as possible. Using an applicator, samples were collected at 0, 15, 30, 60, 90 and 120 min. The sample was placed in a 1.5 mL vial, each containing 200 μL of methylene blue (simple dye) to mix with the sample. Subsequently, 10 μL of the mixed solution was taken and placed in a hemocytometer to count the number of bacteria. According to the counted number, the number of bacteria in each sample was calculated.

[0066] After application of the gel, a reduction in bacteria was observed ( Figure 1 ; n=3).

[0067] Example 3

[0068] A 50-year-old healthy female subject applied the oral care gel product in Table 1 with a soft-bristled toothbrush every night after brushing her teeth before bed for two weeks. After two weeks of continuous use, signs of gum recession were observed to be controlled, and gum inflammation was also reduced.

[0069] While the present disclosure has been described with reference to examples, it should be understood that the scope of the claims should not be limited by the embodiments set forth in the examples, but should be given the broadest interpretation consistent with the overall description.

[0070] All publications, patents, and patent applications cited in this application are incorporated herein by reference in their entirety, to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference in its entirety. If a term is defined in this application differently from a document incorporated herein by reference, the definition provided herein shall govern that term.

Claims

1. An ingestible oral care composition comprising in an aqueous orally acceptable carrier: protein; lipids; polysaccharides and / or their derivatives; and Optional active ingredients.

2. The ingestible oral care composition of claim 1 further comprising a pH neutralizer.

3. An ingestible oral care composition according to claim 1 or 2, wherein the polysaccharide and / or derivative thereof is a combination of arabinogalactan-containing gum, guar gum, xanthan gum and sodium alginate.

4. An ingestible oral care composition according to claim 1 or 2, wherein the polysaccharide and / or derivative thereof is a combination of gum arabic, pectin, guar gum, xanthan gum and sodium alginate.

5. The ingestible oral care composition of claim 1 or 2, wherein the polysaccharide and / or derivative thereof is a combination of gum arabic, guar gum, xanthan gum and sodium alginate.

6. The ingestible oral care composition of claim 3, wherein the arabinogalactan-containing gum is present in an amount from about 0.1 wt% to about 30 wt%; the guar gum is present in an amount from about 0.05 wt% to about 1 wt%; the xanthan gum is present in an amount from about 0.05 wt% to about 1 wt%; and the sodium alginate is present in an amount from about 0.1 wt% to about 10 wt%, based on the total weight of the ingestible oral care composition.

7. The ingestible oral care composition of claim 6, wherein the arabinogalactan-containing gum is gum arabic and is present in an amount from about 1 wt% to about 20 wt%; the guar gum is present in an amount from about 0.05 wt% to about 0.5 wt%; the xanthan gum is present in an amount from about 0.05 wt% to about 0.5 wt%, and the sodium alginate is present in an amount from about 0.5 wt% to about 6 wt%, based on the total weight of the ingestible oral care composition.

8. The ingestible oral care composition of any one of claims 1-7, wherein the protein is gelatin, hydrolyzed collagen, pea protein, soy protein, rice protein, whey protein, or a combination thereof.

9. The ingestible oral care composition of any one of claims 1-8, wherein the protein is a combination of hydrolyzed collagen and gelatin.

10. The ingestible oral care composition of claim 9, wherein the protein is present in an amount of about 0.05 wt% to about 10 wt%, based on the total weight of the ingestible oral care composition.

11. The ingestible oral care composition of any one of claims 1-8, wherein the protein is gelatin.

12. The ingestible oral care composition of claim 11, wherein the gelatin is present in an amount of about 0.1 wt% to about 5 wt%, based on the total weight of the ingestible oral care composition.

13. The ingestible oral care composition of any one of claims 1-12, wherein the lipid is a medium chain triglyceride, grapeseed oil, linseed oil, avocado oil, coconut oil, palm oil, sunflower oil, olive oil, sesame oil, or a combination thereof.

14. The ingestible oral care composition of claim 13, wherein the lipid is present in an amount of about 0.2 wt% to about 27 wt%, based on the total weight of the ingestible oral care composition.

15. The ingestible oral care composition of any one of claims 1-12, wherein the lipid is caprylic / capric triglyceride.

16. The ingestible oral care composition of claim 15, wherein the caprylic / capric triglyceride is present in an amount of about 1 wt% to about 10 wt%, based on the total weight of the ingestible oral care composition.

17. The ingestible oral care composition of any one of claims 2-16, wherein the pH neutralizer is dibasic calcium phosphate anhydrous, dibasic calcium phosphate dihydrate, tricalcium phosphate, or a combination thereof.

18. The ingestible oral care composition of claim 17, wherein the pH neutralizer is present in an amount of about 0.2 wt% to about 3 wt%, based on the total weight of the ingestible oral care composition.

19. The ingestible oral care composition of any one of claims 1-18, wherein the ingestible oral care composition comprises the active ingredient.

20. The ingestible oral care composition of claim 19, wherein the active ingredient comprises a vitamin.

21. The ingestible oral care composition of claim 20, wherein the vitamin is a combination of vitamin C and vitamin B12.

22. The ingestible oral care composition of claim 19, wherein the active ingredient comprises a plant extract.

23. The ingestible oral care composition of claim 19, wherein the active ingredient comprises an essential oil.

24. The ingestible oral care composition of claim 19, wherein the active ingredient comprises a pharmaceutically active compound, a vitamin, a plant extract, an essential oil, or a combination thereof.

25. The ingestible oral care composition of claim 19, wherein the active ingredient comprises a pharmaceutically active compound.

26. Use of the ingestible oral care composition of any one of claims 1-25 for managing gum inflammation in a subject.

27. Use of an ingestible oral care composition according to claim 24 or claim 25 for controlling respiratory disorders through the mouth and throat of a subject.

28. Use of the ingestible oral care composition of any one of claims 1-25 for preventing systemic disease associated with periodontitis in a subject.

29. Use of the ingestible oral care composition of any one of claims 1 to 25 for non-invasively destroying plaque, preventing plaque regeneration, and / or reducing plaque on the oral surfaces of a subject.

30. Use of the ingestible oral care composition of any one of claims 19-25 for delivering an active ingredient to a subject in need thereof.

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