A mucosal adhesion composition comprising a divalent cation donor and a method for curing the same.

Abstract

The present invention comprises (a) a lower alkyl vinyl ether-maleic acid copolymer in a non-neutralized diacid form, (b) a carboxymethylcellulose sodium (Na-CMC) polymer, (c) a water-insoluble and water-swellable cross-linked polyvinylpyrrolidone (PVPP) polymer, and (d) at least one divalent (M ++ The present invention provides a mucosal adhesive composition comprising (a) a cation donor, (e) at least one neutralizing agent, and (f) at least one oral care component. Furthermore, the present invention also provides an in situ curing method at the application site of the mucosal adhesive composition of the claimed invention.

Description

Background Art

[0001] (Related Art) The processes, procedures, methods, products, results, and / or concepts disclosed in the present application (hereinafter collectively referred to as "the present application, the present disclosure, or the present invention") generally relate to mucoadhesive compositions having a divalent cation donor and a neutralizing agent.

[0002] (Background Art) The present invention relates to mucoadhesive compositions having a divalent cation donor and a neutralizing agent.

[0003] Mucosal adhesive compositions, commonly available in the form of creams, powders, or extruded dry wafers / films, including denture fixatives or denture adhesive formulations, are provided and used to provide secure retention of dentures in the oral cavity for users of partial or complete dentures, or to deliver therapeutic active ingredients to desired sites in the oral cavity by topical application. Typically, mucosal adhesive compositions, including denture adhesive creams, consist of water-soluble or water-swellable adhesive polymers suspended in an oral-tolerable carrier matrix, generally composed of varying proportions of long-chain hydrocarbons or long-chain fatty acids such as mineral oil, vegetable oil, or petrolatum. During use, activation of the adhesive components in the mucosal adhesive composition, particularly in denture adhesive creams, occurs upon contact with saliva, resulting in water absorption, swelling, and increased adhesion and tackiness of the denture adhesive formulation applied between the gingiva and the denture. The duration and strength of adhesive retention provided by the denture adhesive formulation are key quantitative performance indicators of denture adhesives. Other semi-quantitative or qualitative indicators used to define the overall performance characteristics of denture adhesive formulations may include the film thickness and cushioning effect provided between the gingiva and the denture by the denture adhesive, the prevention of food particle entry into the interstitial space between the gingiva and the denture by providing excellent sealing of gaps, and the loss of adhesive material from between the gingiva and the denture due to exudation during use. Since general mucosal adhesive compositions, including denture adhesive creams, are essentially suspensions or dispersions of solid active ingredients in a semi-solid or liquid matrix composed of various oils, a decrease in the storage stability of the formulation due to syneresis and separation of the carrier matrix from the solid active ingredients can also adversely affect adhesive performance.

[0004] Therefore, an ideal mucosal adhesive composition, particularly a denture fixing cream, should have adequate storage stability over a long period, provide sufficiently high immediate drying and wetting adhesion and long-lasting adhesive retention during use, ensure a comfortable feel by providing sufficient cushioning between the gums and the denture, seal the gap between the gums and the denture to prevent the entry of food particles, reduce the unpleasant oral sensation caused by the partial hydration of the denture adhesive seeping from between the gums and the denture, and be easy to clean after use.

[0005] U.S. Patent Application Publication No. 20220401395 (owned by ISP Investments LLC) describes a mucoadhesive composition comprising a denture adhesive composition comprising (i) 10 to about 75% by mass of a maleic acid or anhydride copolymer, (ii) 10 to about 50% by mass of a cellulose ether, (iii) 0.1 to 10% by mass of a crosslinked polyvinylpyrrolidone that swells but does not dissolve in water, and (iv) 30 to 70% by mass of an orally acceptable carrier based on the total composition. Also disclosed are its method of use and method of preparation.

[0006] Japanese Patent Registration No. 06908965 (owned by Kobayashi Pharmaceutical Co., Ltd.) discloses a denture stabilizer comprising the following components (A) and (B): (A) at least one adhesion component selected from the group consisting of a lower alkyl vinyl ether / maleic anhydride copolymer, a derivative thereof or a salt thereof, and (B) a hydrogen phosphate.

[0007] International Patent Publication No. 199210988 (owned by Richardson-Vicks, Inc.) discloses an adhesive and stabilizer composition comprising a lower alkyl vinyl ether-maleic acid copolymer and a salt thereof, the copolymer having a specific viscosity of more than 1.2, measured in methyl ethyl ketone at 25°C, the copolymer having a bulk density of about 0.3 to about 1.2 g / cm 3 and a specific surface area of about 0.5 to about 2.5 m 2 / g.

[0008] Based on the above, there is still a need for an ideal mucoadhesive composition that has the advantages of controlled dissolution and activation of the main adhesive polymer, resulting in an extended duration of adhesion / stickiness retention and controlled exudation.

[0009] Surprisingly, due to the hydration of a divalent (M ++ ) cation donor, the divalent (M ++It was found that the in situ generation of cations enables the crosslinking and formation of a stronger interpenetrating network between the lower alkyl vinyl ether-maleic acid copolymer and sodium carboxymethylcellulose, significantly improving the adhesion and / or tackiness of the alkyl vinyl ether-maleic acid copolymer at low concentrations, and further providing better leachate suppression with water-insoluble, water-swellable crosslinked polyvinylpyrrolidone (PVPP). [Overview of the project]

[0010] One aspect of the present application comprises (a) about 2 to about 60% by mass of a lower alkyl vinyl ether-maleic acid copolymer in a non-neutralized diacid form, (b) about 5 to about 60% by mass of a carboxymethylcellulose sodium (Na-CMC) polymer, (c) about 0.5 to about 10% by mass of a water-insoluble, water-swellable crosslinked polyvinylpyrrolidone (PVPP) polymer, and (d) about 0.5 to about 25% by mass of at least one divalent (M ++ The objective is to provide a mucosal adhesive composition comprising (e) a cation donor, (f) at least one neutralizing agent in an amount of about 0.5 to about 25% by mass, and (g) at least one oral-tolerable carrier or oral care component or both in an amount of about 0.001 to about 90% by mass.

[0011] Other aspects of the present invention include (a) about 2 to about 60% by mass of a lower alkyl vinyl ether-maleic acid copolymer in a non-neutralized diacid form, (b) about 5 to about 60% by mass of a carboxymethylcellulose sodium (Na-CMC) polymer, (c) about 0.5 to about 10% by mass of a water-insoluble, water-swellable crosslinked polyvinylpyrrolidone (PVPP) polymer, and (d) about 0.5 to about 25% by mass of at least one divalent (M ++ The objective is to provide a method for in situ curing a mucosal adhesive composition comprising (a) a cation donor, (e) at least one neutralizing agent in an amount of about 0.5 to about 25% by mass, and (f) at least one oral-tolerable carrier or oral care component or both in an amount of about 0.001 to about 90% by mass. The method comprises (a) supplying about 0.01 to about 99.9% by mass of the mucosal adhesive composition to the application site, and (b) curing a divalent (M) in the presence of a hydrate agent.++ ) Divalent (M) in situ by hydration of a cation donor or by introduction of a wettable agent ++ The steps include (c) releasing cations, (d) enabling crosslinking of the lower alkyl vinyl ether-maleic acid copolymer with divalent cations, (e) forming an interpenetrating polymer network (IPN) of the lower alkyl vinyl ether-maleic acid copolymer and carboxymethylcellulose, and (c) obtaining an activated and cured mucosal adhesive composition in situ. [Modes for carrying out the invention]

[0012] Before describing in detail at least one aspect of the disclosed and / or claimed inventive concept, it should be understood that the disclosed and / or claimed inventive concept is not limited to the arrangement, steps, or methodological details of the configuration or components described or shown in the following description or drawings. The disclosed and / or claimed inventive concept may be in other aspects or can be implemented or carried out in various ways. Furthermore, the expressions and terms used herein are for illustrative purposes only and should not be constrained.

[0013] In this disclosure, the following terms shall have the meanings set forth below unless otherwise specified.

[0014] Unless otherwise defined herein, technical terms used in connection with the disclosed and / or claimed inventive concepts shall have the meaning generally understood by those skilled in the art. Furthermore, unless otherwise required by context, singular terms shall include plural forms and plural terms shall include singular forms.

[0015] The singular forms "a," "an," and "the" are considered to include the plural form unless the context clearly indicates otherwise. The terms "comprising" and "comprises of" also encompass more restrictive claims such as "consisting essentially of" and "consisting of."

[0016] For the purposes of the detailed description below, except for the examples, or unless otherwise specified, all numerical values ​​such as the amounts of components described in the detailed description and claims should be understood to be modified by the term "approximately." The numerical parameters described in the detailed description and accompanying claims are approximations that may vary depending on the desired characteristics obtained in the implementation of the invention.

[0017] All percentages, parts, proportions, and ratios used herein are based on the total mass of the composition unless otherwise specified. Therefore, all masses relating to the listed components are based on the active ingredient level and do not include solvents or by-products that may be present in commercially available materials unless otherwise specified.

[0018] All publications, articles, patents, patent publications, and other documents cited herein are incorporated herein by reference in their entirety to the extent consistent with this disclosure for all purposes.

[0019] The term "at least one" should be understood to include, but is not limited to, any quantity of one or more, including 1, 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 100, etc. Depending on the accompanying terminology, the term "at least one" could also extend to 100 or 1000 or more.

[0020] Furthermore, the quantity 100 / 1000 should not be interpreted restrictively, as smaller or larger values ​​may also yield satisfactory results.

[0021] As used herein, “comprising” (and any form of “comprising,” such as “comprise,” “comprises,” etc.), “having” (and any form of “having,” such as “have,” “has,” etc.), “including” (and any form of “including,” such as “includes,” “include,” etc.), or “containing” (and any form of “contains,” “contain,” “contains,” etc., etc.) are inclusive or non-exclusive and do not preclude additional undescribed elements or method steps.

[0022] The phrase "each independently selected from a group consisting of ~" means that when a base appears multiple times in a structure, each occurrence can be independently selected.

[0023] The term "polymer" refers to a compound comprising repeating structural units (monomers) linked by covalent chemical bonds. Polymers can be further modified by derivation, crosslinking, grafting, and end-group modification. Non-limiting examples of polymers include copolymers, terpolymers, quaternary copolymers, quaternary polymers, homologs, etc. The term "polymer" refers to a polymer composed of two or more different types of monomers that are substantially polymerized to obtain the copolymer.

[0024] The terms "denture fixative," "mucosal adhesive," or "denture glue" refer to adhesives that adhere to or bond to the surface of skin, mucous membranes, mucosal cells, or teeth.

[0025] As used herein, “dentures” refers to partial or complete upper or lower dentures, or both. Preferably, the composition should function as an effective means for the thermal insulation, cushioning, and secure positioning of the dentures. The composition is required to retain its properties and characteristics under various climatic conditions, such as temperature and humidity, during storage in powder and cream form, be easy to apply to the surface of the dentures, be non-irritating or uncomfortable to the user, be safe and non-toxic, have no unpleasant odor or color, have no unpleasant taste, do not promote the growth of harmful organisms or microorganisms normally present in the oral cavity, and do not promote the spoilage or generation of foul odors of food or secretions that remain under or adjacent to the dentures.

[0026] As used herein, "diacidic form of lower alkyl vinyl ether-maleic acid copolymer" refers to a process in which approximately 50 mol% maleic anhydride and approximately 50 mol% C1-C4 alkyl vinyl ether are copolymerized in the presence of a free radical initiator at approximately 50°C to 150°C by a solvent or solvent-free process to produce a predetermined weight-average molecular weight of approximately 500,000 to 3,000,000 suitable for denture adhesives, and which is produced as a homogeneous fine powder substantially free of residual maleic anhydride.

[0027] Alkyl vinyl ether-maleic anhydride copolymers are obtained by copolymerizing alkyl vinyl ether monomers such as methyl vinyl ether, ethyl vinyl ether, divinyl ether, propyl vinyl ether, and isobutyl vinyl ether with maleic anhydride, yielding the corresponding alkyl vinyl ether-maleic anhydride copolymer that is readily hydrolyzed to an acidic copolymer. Both the anhydride and acidic forms are available from commercial suppliers. For example, Ashland offers both the polymer-free acidic form and the corresponding anhydride form under the "GANTREZ" trademark as the "GANTREZ S Series".

[0028] As used herein, the term "cellulose ether" refers to a cellulose derivative obtained by etherifying the hydroxyl groups of cellulose using an etherifying agent. Useful cellulose ethers can be selected from the group consisting of methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydrophobically modified hydroxyalkyl cellulose, sodium carboxymethyl cellulose, and mixtures thereof.

[0029] As used herein, the term "monovalent cation" refers to a cation (M + ) having a valence of 1. Thus, the term "divalent cation" refers to a cation (M ++ ) having a valence of 2. Monovalent cations are selected from the group consisting of sodium, potassium, lithium, and combinations thereof. The monovalent cation is sodium. Divalent cations are selected from the group consisting of calcium, magnesium, strontium, iron, zinc, tin, copper, and combinations thereof. More preferably, the divalent cations are calcium, magnesium, zinc, and combinations thereof.

[0030] As used herein, the term "crosslinked or crosslinking" refers to a composition containing intramolecular and / or intermolecular crosslinks, and either covalent or non-covalent bonds can occur. "Non-covalent" bonds include both hydrogen bonds and electrostatic (ionic) bonds.

[0031] As used herein, the term "interpenetrating polymer network" or "IPN" refers to a blend in which two or more polymers are mixed in a network form, and at least one of them is synthesized and / or crosslinked in the immediate presence of another polymer. IPNs can be distinguished from polymer blends, blocks, or grafts in two respects: (1) IPNs swell but do not dissolve in a solvent, and (2) creep and flow are suppressed.

[0032] As used herein, the term "in situ" refers to a specific internal oral cavity location of the skin, mucous membrane, mucosal cells, or denture surface.

[0033] As used herein, the term “functionalized” refers to the presence of a monovalent cation and one or more divalent cations on carboxymethylcellulose. Various monovalent and divalent cations can be introduced into carboxymethylcellulose by one or more functionalization reactions known to those skilled in the art. Non-limiting examples of functionalization reactions include (i) at least one monovalent (M + )Carboxymethylcellulose salt and (ii) one or more divalent (M ++ ) Examples include ion exchange processes involving reactions with metal salts, and divalent (M ++ ) Salt is M ++ Chloride, M ++ Sulfate or M ++ Selected from the group consisting of carbonates, M in CMC polymer + vs M ++ The weight ratio is approximately 1:70 to 70:1.

[0034] Examples of abbreviations used in this specification are shown below. (i) PVP: Polyvinylpyrrolidone; (ii) MVE: Methyl vinyl ether; (iii) MA: Maleic anhydride / maleic acid; (iv) Na-CMC: Sodium carboxymethylcellulose; (v)wt.%: Mass percent; (vi) FlexiThix: lightly to moderately crosslinked polyvinylpyrrolidone; (vii) Polyplasdone XL-10: Self-crosslinking polyvinylpyrrolidone; (viii) PVP K-90: ​​Polyvinylpyrrolidone powder with an average molecular weight of 1,300,000 daltons; (ix) Aqualon CMC 7H3SXF: Sodium carboxymethylcellulose; (x) PVP K-15: Polyvinylpyrrolidone powder with an average molecular weight of 8,000 daltons; and (xi) Other cellulose ethers such as HEC, HPC, EC, and divalent cation-modified cellulose ethers.

[0035] In one non-limiting embodiment, the present application provides (a) about 2 to about 60% by mass of a lower alkyl vinyl ether-maleic acid copolymer in a non-neutralized diacid form, (b) about 5 to about 60% by mass of a carboxymethylcellulose sodium (Na-CMC) polymer, (c) about 0.5 to about 10% by mass of a water-insoluble, water-swellable crosslinked polyvinylpyrrolidone (PVPP) polymer, and (d) about 0.5 to about 25% by mass of at least one divalent (M ++ The present invention provides a mucosal adhesive composition comprising (e) a cation donor, (f) at least one neutralizing agent in an amount of about 0.5 to about 25% by mass, and (e) at least one orally acceptable carrier and / or oral care component in an amount of about 0.001 to about 90% by mass.

[0036] In another non-limiting embodiment, the present application provides a mucosal adhesive composition comprising maleic acid copolymer, maleic acid and about 50 mol% maleic anhydride, and about 50 mol% C1-C 12 A lower alkyl (C3-C3) compound having a predetermined weight-average molecular weight of approximately 500,000 to 3,000,000, is obtained by copolymerizing alkyl vinyl ethers in the presence of a free radical initiator at approximately 50°C to 150°C using a solvent or solvent-free process, thereby producing a homogeneous fine powder that is substantially free of residual maleic anhydride, suitable for denture adhesives. 12 ) Contains vinyl ether.

[0037] In another non-limiting embodiment, the lower alkyl group of the vinyl ether-maleic acid copolymer has 1 to 12 carbon atoms, 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 3 to 6 carbon atoms.

[0038] In another non-limiting embodiment, the methyl vinyl ether-maleic acid (MVE-MA) copolymer has a number-average molecular weight of about 50,000 to about 3,000,000 daltons.

[0039] In another non-limiting embodiment, the lower alkyl groups of the vinyl ether-maleic acid copolymer are approximately 50,000 to approximately 100,000, approximately 300,000 to approximately 500,000, approximately 500,000 to approximately 600,000, approximately 600,000 to approximately 900,000, approximately 900,000 to approximately 1,200,000, and approximately 1,200,000. It has a number-average molecular weight (Daltons) of 0 to approximately 1,500,000, approximately 1,500,000 to approximately 1,800,000, approximately 1,800,000 to approximately 2,100,000, approximately 2,100,000 to approximately 2,500,000, approximately 2,500,000 to approximately 2,800,000, or approximately 2,800,000 to approximately 3,000,000.

[0040] In another non-limiting embodiment, the salt of the alkyl vinyl ether-maleic acid copolymer has a specific viscosity of about 2.5 to about 5.0 when measured as a 1% w / v solution in methyl ethyl ketone (MEK) at 25°C.

[0041] In another non-limiting embodiment, the lower alkyl group of the vinyl ether-maleic acid copolymer has a specific viscosity of about 2.5 to about 3.0, about 3.0 to about 3.5, about 3.5 to about 4.0, about 4.0 to about 4.5, or about 4.5 to about 5.0 when measured as a 1% w / v solution in methyl ethyl ketone (MEK) at 25°C.

[0042] In another non-limiting embodiment, the lower alkyl group of the vinyl ether-maleic acid copolymer is present in an amount of about 5 to about 50% by mass of the total composition. Furthermore, the lower alkyl group of the vinyl ether-maleic acid copolymer is present in an amount of about 5 to about 10% by mass, about 10 to about 15% by mass, about 15 to about 20% by mass, about 20 to about 25% by mass, about 25 to about 30% by mass, about 30 to about 35% by mass, about 35 to about 40% by mass, about 40 to about 45% by mass, or about 45 to about 50% by mass of the total composition.

[0043] In another non-limiting embodiment, the mucosal adhesive composition comprises a sodium salt of carboxymethylcellulose sodium (Na-CMC). A useful cellulose ether herein is the 7H series of carboxymethylcellulose sodium available from Aqualon, which, according to their brochure, has a typical molecular weight of approximately 700,000 daltons. Other useful examples of carboxymethylcellulose include 7H3 SX8F and 7H3 SXF available from Aqualon / Hercules, and CEKOL 30,000P available from CPKelco / Noviant / Huber. In some embodiments, the carboxymethylcellulose sodium used in the described compositions is 7H3SXF.

[0044] In another non-limiting embodiment, the present application discloses that the molecular weight of sodium carboxymethylcellulose is in the medium to high range. In some embodiments, the medium to high weight-average molecular weight is in the range of about 2,000 to about 1,500,000 daltons. In some embodiments, the moderate molecular weight is in the range of about 10,000 to about 15,000 daltons, about 15,000 to about 20,000 daltons, about 20,000 to about 300,000 daltons, about 30,000 to about 40,000 daltons, about 40,000 to about 50,000 daltons, about 50,000 to about 60,000 daltons, about 60,000 to about 70,000 daltons, or about 70,000 to about 80,000 daltons. In the PL embodiment, the molecular weight is approximately 80,000 to 90,000 Daltons, approximately 90,000 to 100,000 Daltons, approximately 100,000 to 200,000 Daltons, approximately 200,000 to 300,000 Daltons, approximately 300,000 to 400,000 Daltons, and approximately 400,000 to 500,000 Daltons. The range is approximately 500,000 to 600,000 Daltons, 600,000 to 700,000 Daltons, 700,000 to 800,000 Daltons, 800,000 to 900,000 Daltons, 900,000 to 1,000,000 Daltons, or 1,000,000 to 1,100,000 Daltons.

[0045] In another non-limiting embodiment, sodium carboxymethylcellulose (Na-CMC) is present in an amount of about 5 to about 60% by mass of the total composition. Furthermore, sodium carboxymethylcellulose (Na-CMC) is present in an amount of about 5 to about 10% by mass, about 10 to about 15% by mass, about 15 to about 20% by mass, about 20 to about 25% by mass, about 25 to about 30% by mass, about 30 to about 35% by mass, about 35 to about 40% by mass, about 40 to about 45% by mass, about 45 to about 50% by mass, about 50 to about 55% by mass, or about 55 to about 60% by mass of the total composition.

[0046] In another non-limiting embodiment, the present application provides a strongly swellable, moderately crosslinked PVP (polyvinylpyrrolidone) polymer, obtained directly as a fine powder by precipitation polymerization of vinylpyrrolidone in an organic solvent in the presence of predetermined amounts of a polyfunctional crosslinking agent and a free radical initiator, trade names FlexiThix® or Polyplasdone®, available from Ashland Inc. The crosslinked PVP has a Brookfield viscosity of at least about 500 to about 50,000 cps in a 4% aqueous solution. Preferred viscosity ranges for the crosslinked PVP in the present application may be about 500 to about 50,000 cps, about 800 to about 20,000 cps, or about 1,000 to about 10,000 cps. The Brookfield viscosity may be measurable at 2.5, 5, 10, 12, 20, 30, or 50 rpm at 25°C.

[0047] Crosslinked PVP polymers useful in the practice of this application can be prepared in accordance with U.S. Patent No. 5,073,614 and U.S. Patent No. 5,130,388, owned by ISP Investments Inc. The disclosures in these documents can be used to the purposes of this application. Furthermore, these documents are incorporated herein by reference in their entirety.

[0048] The elements of the thickening additive composition relating to this application are thickening agents comprising strongly swelling, lightly to moderately crosslinked polyvinylpyrrolidone, as described in the jointly owned U.S. Patents No. 5,312,619 and No. 5,139,770, which are incorporated herein by reference in their entirety. The term “strongly swollen, lightly to moderately crosslinked PVP” specifically refers to a polymer substantially made of lightly to moderately crosslinked poly(N-vinyl-2-pyrrolidone) having, unless otherwise specified, at least one of the following non-limiting properties: (1) a water swelling parameter defined by a gel volume of about 15 mL / g to about 300 mL / g, more particularly about 15 mL / g to about 250 mL / g, or in other cases about 15 mL / g to about 150 mL / g; or (2) a non-limiting property of Brookfield viscosity (measured in 5% crosslinked PVP in a liquid carrier containing water at 25°C) of at least 2,000 cP, more preferably at least about 5,000 cP, and in particular at least about 10,000 cP. References for these parameter ranges are provided in U.S. Patent No. 5,073,614 (incorporated herein by reference) and Shih, JS et al. (1995). Methods for synthesizing crosslinked PVPs are disclosed in numerous publications, including U.S. Patents No. 5,073,614, 5,654,385, and 6,177,068, the details of which are incorporated herein by reference. A polymer scientist skilled in the art will understand that various synthesis methods are possible, provided that the resulting polymer achieves at least one of the parameters defined above.

[0049] Crosslinked polyvinylpyrrolidone is commercially available, for example, from BASF as Kollidon® CL type or from Ashland Inc. as Polyplasdone® XL and Flexithix® type PVP. In other non-limiting embodiments, the application applies to organic solvents, preferably aliphatic hydrocarbons, such as C3-C3, in the presence of predetermined amounts of crosslinking agents and free radical polymerization initiators. 10The present invention provides a swelling crosslinked PVP polymer that can be directly prepared in the form of a fine white powder by precipitation polymerization of vinylpyrrolidone in saturated, branched or unbranched, cyclic or acyclic aliphatic hydrocarbons, most preferably cyclohexane or heptane, or mixtures thereof.

[0050] In various embodiments of the present application, crosslinked polymers of vinylpyrrolidone (including copolymers of vinylpyrrolidone and other monomer materials) that remain in the form of porous granules or beads even when wet and swollen are produced by a process of polymerizing monomer materials with a controlled amount of crosslinking agent in an aqueous solution of an electrolyte. An insoluble polymer is formed, and excess monomer is maintained in a suspended state by mechanical stirring.

[0051] In various embodiments of the present invention, the cross-linked vinylpyrrolidone polymer imparts a certain degree of rigidity to the hydrolyzable denture adhesive, preventing the structural breakdown of the hydrogel and the subsequent loss of the hydrogel due to exudation between the gingiva and the denture during use.

[0052] In other non-limiting embodiments, the present application provides crosslinked polyvinylpyrrolidone (PVPP) present in an amount ranging from about 0.5 to about 10% by mass in the total composition. Thus, the crosslinked polyvinylpyrrolidone (PVPP) is present in an amount ranging from about 0.5 to about 1% by mass, about 1.0 to about 2% by mass, about 2 to about 4% by mass, about 4 to about 6% by mass, about 6 to about 8% by mass, or about 8 to about 10% by mass in the total composition.

[0053] In other non-limiting embodiments, the present application relates to calcium (Ca ++ ), strontium (Sr ++ ), zinc (Zn ++ ), magnesium (Mg ++ ), iron (Fe ++ ), vanadium (V ++ ), chromium (Cr ++ ), manganese (Mn ++ ), nickel (Ni ++ ), copper (Cu ++ ), Yttrium (Y ++) and divalent (M) selected from the group consisting of mixtures thereof ++ ) Provide cation donors.

[0054] In other non-limiting embodiments, divalent (M ++ The cation donor is a salt selected from the group consisting of divalent cation acetates, divalent cation carboxylates, divalent cation glucons, divalent cation halides, divalent cation hydroxides, divalent cation carbonates, divalent cation lactates, divalent cation oxides, divalent cation phosphates, divalent cation sulfates, and combinations thereof.

[0055] In other non-limiting embodiments, divalent (M ++ The cationic salt is selected from the group consisting of calcium acetate, calcium carbonate, calcium chloride, calcium 2-ethylbutanoate, calcium gluconate, calcium hydroxide, calcium lactate, calcium oxide, calcium propionate, calcium sulfate, calcium magnesium acetate, magnesium acetate, magnesium chloride, magnesium propionate, zinc chloride, zinc acetate, and combinations thereof.

[0056] In other non-limiting embodiments, divalent (M ++ )Cation donors are present in the range of approximately 1 to approximately 20% by mass of the total composition. Furthermore, divalent (M ++ The cation donor is present in the total composition in the range of approximately 1 to 5% by mass, approximately 5 to 10% by mass, approximately 10 to 15% by mass, or approximately 15 to 20% by mass.

[0057] In other non-limiting embodiments, the neutralizing agent is monovalent (M + ) Cation or divalent (M ++ ) Cation hydroxide salt, monovalent (M + ) Cation or divalent (M ++) A salt selected from the group consisting of cation phosphates, monovalent or divalent cation pyrophosphates, monovalent or divalent cation hydrogen phosphates, monovalent or divalent cation carbonates or bicarbonates, monovalent or divalent cation tripolyphosphates or orthometaphosphates, monovalent or divalent cation hydroxides, and combinations thereof.

[0058] In various embodiments of the present invention, the neutralizing agent is monovalent (M + ) Cation or divalent (M ++ ) Selected from the group consisting of cation phosphates, monovalent or divalent cation pyrophosphates, monovalent or divalent cation hydrogen phosphates, monovalent or divalent cation carbonates or bicarbonates, monovalent or divalent cation orthometaphosphates, and combinations thereof.

[0059] Therefore, the neutralizing agent is selected from the group consisting of sodium hydroxide, sodium orthometaphosphate, sodium hydrogen phosphate, trisodium phosphate, sodium tripolyphosphate, tetrasodium pyrophosphate, sodium hexametaphosphate, potassium hydroxide, potassium hydrogen phosphate, and mixtures thereof.

[0060] In other non-limiting embodiments, the neutralizing agent is present in an amount ranging from about 0.5% to about 20% by mass of the total composition. Furthermore, the neutralizing agent is present in an amount ranging from about 0.5% to 5% by mass, about 5% to about 10% by mass, about 10% to about 15% by mass, or about 15% to about 20% by mass of the total composition.

[0061] In other non-limiting embodiments, the present application further comprises at least one additional cellulose polymer selected from the group consisting of lower alkylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, divalent cation-modified carboxymethylcellulose, and mixtures thereof, in an amount of about 0.5 to about 60% by mass of the total composition.

[0062] In other non-limiting embodiments, the present application further comprises at least one additional cellulose polymer in the range of about 0.5 to about 5% by mass, about 5 to about 10% by mass, about 10 to about 15% by mass, about 15 to about 20% by mass, about 20 to about 25% by mass, about 25 to about 30% by mass, about 30 to about 35% by mass, about 35 to about 40% by mass, about 40 to about 45% by mass, about 45 to about 50% by mass, about 50 to about 55% by mass, and about 55 to about 60% by mass of the total composition.

[0063] Therefore, the additional cellulose polymer has a weight-average molecular weight in the range of about 2,000 to about 1,500,000 daltons. In some embodiments, the intermediate molecular weight is in the range of about 10,000 to about 15,000 daltons, or about 15,000 to about 20,000 daltons, or about 20,000 to about 300,000 daltons, or about 30,000 to about 40,000 daltons, or about 40,000 to about 50,000 daltons, or about 50,000 to about 60,000 daltons, or about 60,000 to about 70,000 daltons, or about 70,000 to about 80,000 daltons. In the spectral embodiment, the molecular weight is approximately 80,000 to 90,000 Daltons, or approximately 90,000 to 100,000 Daltons, or approximately 100,000 to 200,000 Daltons, or approximately 200,000 to 300,000 Daltons, or approximately 300,000 to 400,000 Daltons, or approximately 400,000 to 500,000 Daltons, or approximately 500,000 to 600,000 Daltons, or approximately 600,000 to 700,000 Daltons, and The range is approximately 700,000 to 800,000 Daltons, or approximately 800,000 to 900,000 Daltons, or approximately 900,000 to 1,000,000 Daltons, approximately 1,000,000 to 1,100,000 Daltons, approximately 1,100,000 to 1,200,000 Daltons, approximately 1,200,000 to 1,300,000 Daltons, approximately 1,300,000 to 1,400,000 Daltons, or approximately 1,400,000 to 1,500,000 Daltons.

[0064] In other non-limiting embodiments, the present application relates to carboxymethylcellulose (CMC), i) at least one monovalent (M + ) cation and at least one divalent (M ++ The additional cellulose polymers provided are (i) functionalized with a cation, and (ii) functionalized with at least one divalent cation. The additional cellulose polymers include (i) sodium-calcium carboxymethylcellulose (Na + -Ca ++ -CMC), (ii) Sodium-magnesium carboxymethylcellulose (Na + -Mg ++ -CMC), (iii) sodium-zinc carboxymethylcellulose (Na + -Zn ++ -CMC), (iv) sodium-calcium-zinc carboxymethylcellulose (Na + -Ca ++ -Zn ++ -CMC), (v) Sodium-Calcium-Magnesium Carboxymethylcellulose (Na + -Ca ++ -Mg ++ -CMC), (vi) sodium-magnesium-zinc carboxymethylcellulose (Na + -Mg ++ -Zn ++ -CMC), (vii) Sodium-tin carboxymethylcellulose (Na + -Sn ++ -CMC), (viii) sodium-calcium-tin carboxymethylcellulose (Na + -Ca ++ -Sn ++ -CMC), (ix) Sodium-Magnesium-Tin Carboxymethylcellulose (Na + -Mg ++ -Sn ++ -CMC), (x) sodium-zinc-tin carboxymethylcellulose (Na + -Zn ++ -Sn ++ -CMC), (xi) Calcium Carboxymethylcellulose (Ca ++-CMC), (xii) Magnesium Carboxymethylcellulose (Mg ++ -CMC), (xiii) Zinc carboxymethylcellulose (Zn ++ -CMC), or (xiv) tin carboxymethylcellulose (Sn ++ It is carboxymethylcellulose (CMC) selected from the group consisting of -CMC.

[0065] In other non-limiting embodiments, the mucosal adhesion composition of the present invention provides one or more oral care-acceptable components selected from the group consisting of adhesion promoters, modified cellulose ethers, anticaking agents, antifungal agents, antibacterial agents, antigingivitis agents, anesthetics, antioxidants, antibiotics, anti-inflammatory agents, binders, buffers, colorants, cooling agents, dentin hypersensitivity inhibitors, dispersants, enzymes, softeners, flavoring agents, fillers, fragrances, gelling agents, wetting agents, hydrophilic non-oily components, oily carriers, exudation-inhibiting polymers, preservatives, pigments, plasticizers, analgesics, sweeteners, thickeners, viscosity modifiers, solvents, surfactants, stabilizers, sensory agents, and mixtures thereof.

[0066] In other embodiments, the oral care-friendly component is present in an amount of about 0.001 to about 90% by mass of the total composition. Furthermore, the oral care component is present in an amount of about 0.001 to about 10% by mass, about 10 to about 20% by mass, about 20 to about 30% by mass, about 30 to about 40% by mass, about 40 to about 50% by mass, about 50 to about 60% by mass, about 60 to about 70% by mass, about 70 to about 80% by mass, and about 80 to about 90% by mass of the total composition.

[0067] Non-specific examples of softening agents include hydrophobic oils or hydrophilic non-oily components.

[0068] Therefore, hydrophobic oils or hydrophilic non-oil components may be selected from the group consisting of liquid petrolatum, petrolatum, mineral oil, glycerin, natural and synthetic oils and fats, fats, silicones and silicone derivatives, polyvinyl acetate, polyethylene glycol, propylene glycol, polypropylene glycol, poly(ethylene oxide-propylene oxide) copolymer, diethylene glycol, triethylene glycol, sorbitol, water, orally acceptable surfactants and mixtures thereof, animal waxes such as beeswax, lanolin, and shellac, hydrocarbons, hydrocarbon derivatives, natural and synthetic waxes such as vegetable oil waxes such as carnauba, candela, and bayberry, vegetable oils such as caprylic / capric triglyceride, vegetable oils such as corn oil, sunflower oil, soybean oil, castor oil, palm oil, coconut oil, olive oil, and rapeseed oil or mixtures thereof, animal oils such as fish oil, oleic acid, and mixtures thereof. Non-specific examples of mineral oils include maleized avocado oil, maleized coconut oil, maleized corn oil, maleized cottonseed oil, maleized jojoba oil, maleized linseed oil, maleized nut oil, maleized olive oil, maleized palm oil, maleized raisin oil, maleized rapeseed oil, maleized safflower oil, maleized sesame oil, maleized soybean oil, maleized pumpkin oil, maleized sunflower oil, maleized almond oil, maleized canola oil, maleized flaxseed oil, maleized grapeseed oil, maleized palm oil, maleized palm kernel oil, maleized peanut oil, and maleized walnut oil.

[0069] In other non-limiting embodiments, the mineral oil is functionalized or non-functionalized maleated soybean oil, where the functionalization includes hydrophilic or hydrophobic moieties.

[0070] In some embodiments, the hydrophobic oil or hydrophilic non-oil component-based carrier is present in appropriate amounts of about 10% to about 20% by mass, about 20% to about 30% by mass, about 30% to about 40% by mass, about 40% to about 50% by mass, about 50% to about 60% by mass, or about 60% to about 75% by mass, relative to the total weight of the mucosal adhesive composition, which includes the denture adhesive composition.

[0071] Non-limiting examples of colorants are selected from the group consisting of talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, aluminum magnesium silicate, silica, titanium dioxide, zinc oxide, red iron oxide, brown iron oxide, yellow iron oxide, black iron oxide, ferric ammonium ferrocyanide, manganese violet, ultramarine, nylon powder, polyethylene powder, methacrylate powder, polystyrene powder, silk powder, crystalline cellulose, starch, titanium mica, titanium iron mica oxide, bismuth chloride oxide, and mixtures thereof.

[0072] Non-limiting examples of flavorings include (i) synthetic flavoring liquids and / or oils derived from plant leaves, flowers, and fruits, including vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, wintergreen oil (methyl salicylate), peppermint oil, clove oil, bay oil, anise oil, and eucalyptus oil; (ii) artificial, natural, or synthetic fruit flavors extracted from lemon, orange, banana, grape, lime, apricot, and grapefruit; (iii) fruit essences prepared from apple, strawberry, cherry, orange, and pineapple; (iv) flavors prepared from legumes and nuts, including coffee, cocoa, cola, peanuts, and almonds; (v) flavorings adsorbed onto hydrophilic matrices, such as "spray-dried" flavorings; and (vi) encapsulated flavorings.

[0073] The amount of flavoring agent used is usually a matter of preference, depending on factors such as the type of flavor and the desired intensity of the flavor. Flavoring agents may be present in amounts of up to about 4% of the total composition by weight, about 0.05% to about 3.0% in one embodiment, and about 0.8% to about 2.5% in other embodiments.

[0074] Non-limiting examples of antimicrobial compounds used in this composition include halogenated diphenyl ethers (e.g., triclosan), herbal extracts and essential oils (e.g., rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitiol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak extract, sea buckthorn extract), biguanide preservatives (e.g., chlorhexidine, alexidine, or octenidine), and quaternary ammonium compounds (e.g., cetylpyridinium chloride (CPC), benzyl ammonium compounds). The following substances are selected from the group consisting of salkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl-4-ethylpyridinium chloride (TDEPC), phenolic preservatives, hexetidine, octenidine, sanguinarin, povidone-iodine, dermopinol, salifluol, metal ions (e.g., zinc salts such as zinc chloride, zinc lactate, zinc sulfate, tin salts, copper salts, iron salts), sanguinarin, propolis, stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluorides, and ammonium fluoride. The anti-inflammatory compounds of this application may be selected from the group including, but not limited to, triamcinolone (trade name: Kenalog), fluocinonide (trade name: Banos), dexamethasone (trade name: Decadron), herpes, amlexanox (Aftasol), ketrolac, flurbiprofen, ibuprofen, naproxen, indomethacin, aspirin, ketoprofen, piroxicam, and meclofenamic acid.

[0075] Non-limiting examples of analgesic compounds of this application may be selected from the group including, but not limited to, benzocaine, lidocaine, procaine, prilocaine, mepivacaine, aspirin, ibuprofen, diclofenac, and methyl salicylate.

[0076] Non-limiting examples of antioxidant compounds of this application may be selected from the group including, but not limited to, vitamin E, ascorbic acid, uric acid, carotenoids, vitamin A, flavonoids, polyphenols, herbal antioxidants, melatonin, aminoindole, lipoic acid, caffeic acid, β-carotene, ellagic acid, epicatechin, epicatechin gallate, ferulic acid, genistein, kojic acid, α-lipoic acid, lycopene, resveratrol, resorcinol, rosmarinic acid, silibinin, theaflavin, tocopherol, tocotrienol, trolox, and ubiquinone-10.

[0077] Non-limiting examples of enzymes of the present invention may be selected from the group including, but not limited to, the proteases papain, bromelain, chymotrypsin, ficin, and alcalase; the carbohydrases glucoamylase, α-amylase, β-amylase, dextranase, and mutanase; the lipases plant lipase, gastric lipase, and pancreatic lipase; and the glucoamylase saccharified glucoamylase derived from Aspergillus oryzae.

[0078] Non-limiting examples of the cooling agents of this application include, but are not limited to, menthol, menthoxy lactic acid, monomentyl succinic acid, menthol ethylene glycol carbonate, menthol propylene glycol carbonate, menthone-glycerol ketal, 3-(1-menthoxy)propane-1,2-diol, (-)-isoplegol, WS-3 [N-ethyl-p-menthane-3-carboxamide], WS-23 (2-isopropyl-N-2,3-trimethylbutylamide), and WS-5 [ethyl 3p-menthane-3-carboxamide) acetate], and may be selected from the group.

[0079] The cooling agent of this application may be selected from the group including, but not limited to, acesulfame K, aspartame, neotame, saccharin, sucralose, stevia, advantame, cyclamate, sorbitol, xylitol, and erythritol.

[0080] In some embodiments, antibacterial agents, anti-inflammatory agents, analgesics, antioxidants, enzymes, flavoring agents, cooling agents, and sweeteners are present in appropriate amounts of about 0.01% to about 0.1% by mass, or about 0.1% to about 1% by mass, or about 1% to about 10% by mass, or about 10% to about 20% by mass, based on the total weight of the mucosal adhesive composition, which includes the denture adhesive and denture fixative composition.

[0081] Other embodiments of the present application envision the use of at least one excipient. Excipients suitable for the purposes of the present application are selected from the group consisting of preservatives, fragrances, colorants, sweeteners, plasticizers, binders, thickeners, solvents, colorants, carriers, flavoring agents, fragrances, sensory agents, and mixtures thereof.

[0082] In other non-limiting embodiments, the present application discloses the manufacture of mucosal adhesive compositions for the sustained release of active ingredients selected from the group including, but not limited to, antimicrobial agents, anti-inflammatory agents, analgesics, antioxidants, enzymes, flavoring agents, cooling agents, and sweeteners, and the use of such formulations.

[0083] In one embodiment, the mucosal adhesive composition is an oral gel, oral ointment, cheek composition, sublingual composition, palate composition, and denture adhesive composition, and is in the form of toothpaste, denture cleaner, chewing gum, lozenges, mice, dental instruments, toothpaste powder, topical oral gel, denture products, soluble films, strips, oral tablets, wafers, and chewing gum.

[0084] In one embodiment, it is envisioned that a material suitable for mucosal adhesion compositions including denture adhesives is used, in particular, the material being a paste, cream, gel, thermoplastic solid, hydrogel or a combination thereof, which is safe and palatable at the relevant concentrations for use in hygienic compositions.

[0085] In other non-limiting embodiments, the mucosal adhesive composition of the present invention has a pH of about 5 to about 8.

[0086] In other non-limiting embodiments, the present application provides (a) about 2 to about 60% by mass of a lower alkyl vinyl ether-maleic acid copolymer in a non-neutralized diacid form, (b) about 5 to about 60% by mass of a carboxymethylcellulose sodium (Na-CMC) polymer, (c) about 0.5 to about 10% by mass of a water-insoluble, water-swellable crosslinked polyvinylpyrrolidone (PVPP) polymer, and (d) about 0.5 to about 25% by mass of at least one divalent (M ++ The present invention provides an in situ curing method for a mucosal adhesive composition comprising (a) a cation donor, (e) at least one neutralizing agent in an amount of about 0.5 to about 25% by mass, and (f) at least one oral-tolerable carrier and / or oral care component in an amount of about 0.001 to about 90% by mass, the method comprising (a) supplying about 0.1 to about 99.9% by mass of the mucosal adhesive composition to the application site, and (b) curing in the presence or introduction of a divalent (M) cation donor. ++ ) Divalent (M) in situ by hydration of the cation donor ++ The steps include (c) releasing cations, (d) enabling crosslinking of the lower alkyl vinyl ether-maleic acid copolymer with divalent cations, (e) forming an interpenetrating polymer network (IPN) of the lower alkyl vinyl ether-maleic acid copolymer and carboxymethylcellulose, and (c) obtaining an activated and cured mucosal adhesive composition in situ.

[0087] Therefore, the wettable powder is either water or saliva.

[0088] In other non-limiting embodiments, the mucosal adhesive composition is a denture fixing agent composition.

[0089] Furthermore, specific embodiments of the present application are illustrated in detail by the following examples. These examples are provided herein for illustrative purposes only, and are not intended to limit the present application. [Examples]

[0090] (Example 1: Oily mucosal adhesion formulation)

[0091] A 200g batch of standard oily mucosal adhesive formulation was prepared in a KitchenAid planetary mixer equipped with a digitally controlled constant-temperature heating jacket. The heating jacket was set to a constant temperature of 194°F (90°C). The necessary components for preparing the mucosal adhesive cream were added according to Table 1. Petrolatum and white mineral oil were added to the heated bowl of the KitchenAid mixer and mixed at low speed for 10 minutes until the petrolatum was completely dissolved, producing a homogeneous clear liquid. Sodium carboxymethylcellulose was added to the KitchenAid and mixed vigorously with the oil for 30 minutes until uniformly dispersed. If necessary, other cellulose ethers were also added to the KitchenAid mixing bowl and mixed vigorously for another 10 minutes. Next, poly(MVE / MA) diacid polymer powder was added to the KitchenAid and mixed at medium speed for another 10 minutes to obtain a homogeneous paste. The neutralizing agent, divalent cation donor, and exudation inhibitor were added to a KitchenAid mixing bowl as shown in Table 1, and then vigorously mixed for 30 minutes until a uniform paste was obtained. Appropriate colorants and other ingredients were added and mixed until uniformly dispersed. Heating was stopped, and the mucosal adhesive cream was cooled to room temperature over 2 hours with continuous stirring at medium speed. After cooling to room temperature, 50 g of the mucosal adhesive sample was filled into a suitable dispensing tube and heat-sealed. The remaining mucosal adhesive formulation was filled into a clear glass bottle and used for storage stability testing.

[0092] (Example 2: Method for testing mucosal adhesion)

[0093] Adhesion strength and relative mucosal adhesion film thickness were recorded using a TA.XT Plus texture analyzer system from Stable Microsystems Texture Technologies Corp., equipped with a 50kg load cell and connected to a PC running Exponent software version 6.1.11.0. The texture analyzer system featured a custom-made denture-shaped plexiglass probe-fixture assembly. Artificial saliva was injected into the interwalls of the plexiglass probe-fixture assembly using a peristaltic pump. Real-time time-lapse images during the evaluation of the adhesive performance of the mucosal adhesion cream on the texture analyzer system were recorded with a Canon EOS 5D Mark IV digital SLR camera.

[0094] Sample tubes containing a mucosal-adhering cream were de-aired and the caps were removed, then the tubes were squeezed several times to homogenize the contents. The first 100 mg of material dispensed from each tube was always discarded.

[0095] Three nearly identical strips of mucosal adhesive cream were weighed onto the denture-shaped cavity of the lower plexiglass fixture on an analytical balance. The total mass of mucosal adhesive cream applied to the lower fixture in each test was 2.0 (+0.1) g. The lower fixture was mounted on a texture analyzer, and the upper probe was lowered into the cavity of the lower fixture. Under a precise compressive force of 4.5 kg, the mucosal adhesive cream was evenly spread and filled the lower half of the cavity. The injection of artificial saliva was started. Throughout the entire experiment, the mucosal adhesive cream remained in constant contact and immersed beneath a thin layer of artificial saliva, which was continuously supplied with fresh artificial saliva at a flow rate of 1 ml / min. The test sequence was started 7 hours after the mucosal adhesive cream layer was completely covered with artificial saliva. The adhesive force during chewing (in Newtons) and the thickness of the mucosal adhesive film between the upper and lower probes (in mm) were measured continuously throughout the experiment. Four consecutive experiments were conducted on each prepared mucosal adhesion formulation sample. The average plot of the four experiments for each sample was compared for adhesion performance and thickness variation. The total adhesion strength for each sample (Examples 1, 4, 7-9, 14-18, 20, and 21) was calculated as the area under the curve of the average plot of the four consecutive experiments and is shown in Table 1.

[0096] [Table 1]

[0097] The above description fully discloses the present invention, including preferred embodiments. Modifications and improvements to the embodiments specifically disclosed herein are included within the scope of the appended claims. Those skilled in the art will be able to make the most of the present invention based on the above description without requiring any further detailed description. Embodiments of the present invention for which exclusive rights or privileges are claimed are defined as appended.

Claims

1. (a) A lower alkyl vinyl ether-maleic acid copolymer in a non-neutralized diacid form, in an amount of approximately 2 to approximately 60% by mass, (b) Approximately 5 to approximately 60% by mass of carboxymethylcellulose sodium (Na-CMC) polymer, (c) Approximately 0.5 to approximately 10% by mass of water-insoluble, water-swellable cross-linked polyvinylpyrrolidone (PVPP) polymer, (d) At least one divalent (M) in about 0.5 to about 25% by mass ＋＋ ) Cation donor and, (e) at least one neutralizing agent in an amount of approximately 0.5 to approximately 25% by mass, (f) At least one oral care component in an amount of approximately 0.001 to approximately 90% by mass, A mucosal adhesion composition comprising the following features.

2. The mucosal adhesive composition according to claim 1(a), wherein the lower alkyl group of the vinyl ether-maleic acid copolymer has about 1 to about 12 carbon atoms.

3. The mucosal adhesive composition according to claim 1(a), wherein the lower alkyl group of the vinyl ether-maleic acid copolymer has about 1 to about 8 carbon atoms.

4. The mucosal adhesive composition according to claim 3, wherein the lower alkyl vinyl ether-maleic acid copolymer is selected from the group consisting of methoxyethylene maleic acid copolymer, ethyl vinyl ether maleic acid copolymer, propyl vinyl ether maleic acid copolymer, isobutyl vinyl ether maleic acid copolymer, and mixtures thereof.

5. The mucosal adhesive composition according to claim 1(a), wherein the average molecular weight of the lower alkyl vinyl ether-maleic acid copolymer is in the range of about 50,000 to about 3,000,000 daltons.

6. The mucosal adhesive composition according to claim 1(a), wherein the lower alkyl vinyl ether-maleic acid copolymer has a specific viscosity of about 2.5 to about 5.0% when measured as a 1% w / v solution in methyl ethyl ketone (MEK) at 25°C.

7. The mucosal adhesive composition according to claim 1(a), wherein the lower alkyl vinyl ether-maleic acid copolymer is present in an amount of about 5 to about 50% by mass of the total composition.

8. The mucosal adhesive composition according to claim 1(b), wherein the carboxymethylcellulose sodium has a number-average molecular weight in the range of about 50,000 to about 1,000,000 daltons.

9. The mucosal adhesive composition according to claim 1(b), wherein the carboxymethylcellulose sodium is present in an amount of about 5 to about 60% by mass of the total composition.

10. The mucosal adhesive composition according to claim 1(c), wherein the cross-linked polyvinylpyrrolidone (PVPP) has a gel volume of about 15 to about 300 ml / g.

11. The mucosal adhesive composition according to claim 1(c), wherein the cross-linked polyvinylpyrrolidone (PVPP) is present in an amount of about 0.5 to about 10% by mass of the total composition.

12. The divalent (M ＋＋ ) cation donor is calcium (Ca ＋＋ ), strontium (Sr ＋＋ ), zinc (Zn ＋＋ ), magnesium (Mg ＋＋ ), iron (Fe ＋＋ ), vanadium (V ＋＋ ), chromium (Cr ＋＋ ), manganese (Mn ＋＋ ), nickel (Ni ＋＋ ), copper (Cu ＋＋ ), yttrium (Y ＋＋ ) salts and mixtures thereof, and the mucoadhesive composition according to claim 1(d).

13. The aforementioned divalent (M ＋＋ The mucosal adhesive composition according to claim 1(d), wherein the cation donor is a salt selected from the group consisting of divalent cation acetate, divalent cation carboxylate, divalent cation gluconate, divalent cation halide, divalent cation hydroxide, divalent cation lactate, divalent cation oxide, divalent cation phosphate, divalent cation sulfate, and combinations thereof.

14. Divalent (M ＋＋ The mucosal adhesive composition according to claim 13, wherein the cationic salt is selected from the group consisting of calcium acetate, calcium carbonate, calcium chloride, calcium 2-ethylbutanoate, calcium gluconate, calcium hydroxide, calcium lactate, calcium oxide, calcium propionate, calcium sulfate, calcium magnesium acetate, magnesium acetate, magnesium chloride, magnesium propionate, zinc sulfate, zinc chloride, zinc acetate, and combinations thereof.

15. The aforementioned divalent (M ＋＋ The mucosal adhesive composition according to claim 1(d), wherein the cation donor is present in an amount of about 1 to about 20% by mass of the total composition.

16. The neutralizing agent is calcium (Ca ＋＋ ), sodium (Na ＋ ), strontium (Sr ＋＋ ), zinc (Zn ＋＋ ), magnesium (Mg ＋＋ ), iron (Fe ＋＋ ), potassium (K ＋ ), vanadium (V ＋＋ ), chromium (Cr ＋＋ ), manganese (Mn ＋＋ ), nickel (Ni ＋＋ ), copper (Cu ＋＋ ), Yttrium (Y ＋＋ ) and monovalent (M) selected from the group consisting of mixtures thereof ＋ ) Cation or divalent (M ＋＋ The mucosal adhesive composition according to claim 1(e), which is a salt of a cation.

17. The neutralizing agent is monovalent (M ＋ ) Cation or divalent (M ＋＋ The mucosal adhesive composition according to claim 1(e), selected from the group consisting of cation hydroxides, monovalent or divalent cation phosphates, monovalent or divalent cation pyrophosphates, monovalent or divalent cation hydrogen phosphates, monovalent or divalent cation carbonates or bicarbonates, monovalent or divalent cation tripolyphosphates or orthometaphosphates, monovalent or divalent cation hydroxides, and combinations thereof.

18. The mucosal adhesion composition according to claim 17, wherein the neutralizing agent is selected from the group consisting of sodium hydroxide, sodium orthometaphosphate, sodium hydrogen phosphate, trisodium phosphate, sodium tripolyphosphate, tetrasodium pyrophosphate, sodium hexametaphosphate, potassium hydroxide, potassium hydrogen phosphate, and mixtures thereof.

19. The mucosal adhesive composition according to claim 1(e), wherein the neutralizing agent is present in an amount of about 0.5 to about 20% by mass of the total composition.

20. The mucosal adhesive composition according to claim 1, further comprising about 0.5 to about 60% by mass of at least one additional cellulose polymer selected from the group consisting of lower alkylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, divalent cation-modified carboxymethylcellulose, and mixtures thereof.

21. The mucosal adhesive composition according to claim 20, wherein the additional cellulose polymer has a weight-average molecular weight in the range of about 2,000 to about 1,500,000 daltons.

22. The divalent cation-modified carboxymethylcellulose (CMC) (i) has at least one monovalent (M ＋ ) cation and at least one divalent (M ＋＋ ) with a cation, or (ii) the following, (i) Sodium-calcium carboxymethylcellulose (Na ＋ -Ca ＋＋ -CMC), (ii) Sodium-magnesium carboxymethylcellulose (Na ＋ -Mg ＋＋ -CMC), (iii) Sodium-zinc carboxymethylcellulose (Na ＋ -Zn ＋＋ -CMC), (iv) Sodium-Calcium-Zinc Carboxymethylcellulose (Na ＋ -Ca ＋＋ -Zn ＋＋ -CMC), (v) Sodium-Calcium-Magnesium Carboxymethylcellulose (Na ＋ -Ca ＋＋ -Mg ＋＋ -CMC), (vi) Sodium-magnesium-zinc carboxymethylcellulose (Na ＋ -Mg ＋＋ -Zn ＋＋ -CMC), (vii) Sodium tin carboxymethylcellulose (Na ＋ -Sn ＋＋ -CMC), (viiii) Sodium-calcium-tin carboxymethylcellulose (Na ＋ -Ca ＋＋ -Sn ＋＋ -CMC), (ix) Sodium-magnesium-tin carboxymethylcellulose (Na ＋ -Mg ＋＋ -Sn ＋＋ -CMC), (x) Sodium-zinc-tin carboxymethylcellulose (Na ＋ -Zn ＋＋ -Sn ＋＋ -CMC), (xi) Calcium carboxymethylcellulose (Ca ＋＋ -CMC), (xi) Magnesium carboxymethylcellulose (Mg ＋＋ -CMC), (xiiii) Zinc carboxymethylcellulose (Zn ＋＋ -CMC), or, (xiv) Tin carboxymethylcellulose (Sn ＋＋ -CMC), Functionalized with at least one divalent cation selected from the group consisting of, The mucosal adhesive composition according to claim 20.

23. The mucosal adhesive composition according to claim 1(f), wherein the one or more oral care-permissible components are selected from the group consisting of adhesion promoters, additionally modified cellulose ethers, anticaking agents, antifungal agents, antibacterial agents, antigingivitis agents, anesthetic agents, antioxidants, antibiotics, anti-inflammatory agents, binders, buffers, colorants, cooling agents, dentin hypersensitivity inhibitors, dispersants, enzymes, softeners, flavoring agents, fillers, fragrances, gelling agents, wetting agents, hydrophilic non-oily components, oily carriers, exudation-inhibiting polymers, preservatives, pigments, plasticizers, analgesics, sweeteners, thickeners, viscosity modifiers, solvents, surfactants, stabilizers, sensory agents, and mixtures thereof.

24. The mucosal adhesive composition according to claim 1(f), wherein the one or more oral care-permissible components are present in an amount of about 0.001 to about 90% by mass of the total composition.

25. The mucosal adhesion composition according to claim 1, wherein the softening agent is selected from the group consisting of petrolatum, mineral oil, olive oil, vegetable oil, silicone or glycerin, polyethylene glycol, propylene glycol, poly(ethylene oxide-propylene oxide) copolymer, diethylene glycol, triethylene glycol, sorbitol, water, oral-friendly surfactants, and mixtures thereof, and the softening agent is present in an amount of about 0.1 to about 60% by mass of the total oral care components.

26. The mucosal adhesive composition according to claim 1, wherein the coloring agent is selected from the group consisting of talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, aluminum magnesium silicate, silica, titanium dioxide, zinc oxide, red iron oxide, brown iron oxide, yellow iron oxide, black iron oxide, ferric ammonium ferrocyanide, manganese violet, ultramarine, nylon powder, polyethylene powder, methacrylate powder, polystyrene powder, silk powder, crystalline cellulose, starch, titanium mica, titanium iron mica oxide, bismuth chloride, and mixtures thereof.

27. The mucosal adhesive composition according to claim 1, wherein the flavoring agent is selected from (i) synthetic flavoring liquids and / or oils derived from the leaves, flowers, and fruits of plants, including vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, wintergreen oil (methyl salicylate), peppermint oil, clove oil, bay oil, anise oil, and eucalyptus oil; (ii) artificial, natural, or synthetic fruit flavors extracted from lemon, orange, banana, grape, lime, apricot, and grapefruit; (iii) fruit essences prepared from apple, strawberry, cherry, orange, and pineapple; (iv) flavors derived from legumes and nuts, including coffee, cocoa, cola, peanut, and almond; (v) flavoring agents adsorbed onto a hydrophilic matrix such as "spray-dried" flavoring agents; and (vi) encapsulated flavoring agents.

28. The composition is a mucosal adhesion composition according to claim 1, having a pH of about 5 to about 8.

29. The mucosal adhesive composition according to claim 1, wherein the composition is formulated as an ointment, solid, semi-solid, emulsion, powder, paste, dispersion, gel, or patch.

30. (a) The step of supplying the mucosal adhesive composition according to claim 1 in an amount of about 0.01 to about 99.9% by mass to the application site, (b) Divalent (M) in the presence or introduction of a wettable powder ＋＋ ) By hydrating the cation donor, a divalent (M) is produced in situ. ＋＋ ) A step of releasing a cation, (c) A step that enables crosslinking of the lower alkyl vinyl ether-maleic acid copolymer by divalent cations, (d) The step of forming an interpenetrating polymer network (IPN) of a lower alkyl vinyl ether-maleic acid copolymer and carboxymethylcellulose, (e) The step of obtaining the mucosal adhesive composition according to claim 1 which has been activated and cured in situ, An in situ curing method for the mucosal adhesive composition according to claim 1, comprising:

31. The in situ curing method for the mucosal adhesive composition according to claim 30, wherein the wettable agent is water or saliva.

32. The mucosal adhesive composition according to claim 1, wherein the mucosal adhesive composition is a denture fixing agent or a denture adhesive composition.

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