Solid adhesive composition

Abstract

New adhesive compositions are provided which have improved performance, such as higher strength and / or longer duration and / or combating malodour, when in contact with human mucous membranes. (a) at least one active agent; (b) at least one carrier, and (c) at least one adhesive polymer, wherein the carrier is selected from the group consisting of silicon dioxide, silica gel, and silicates.

Description

[Technical field]

[0001] The present invention relates to the field of oral care formulations and to a novel solid adhesive composition, its preparation method and its use. [Background technology]

[0002] Flavors and fragrances generally exhibit unfavourable deposition and release profiles on physiological surfaces, so either the concentration of the substance used is increased or highly effective agents are used to improve the intensity and / or duration of the taste or smell, or further the sensory perception.

[0003] However, there remains a problem that the senses can only be controlled to a limited extent, and the duration and intensity of sensations can only be measured laboriously in vivo.

[0004] WO 2005 / 023363 relates in particular to a sheet-like, rapidly disintegrating or soluble in an aqueous environment dosage form for rapid release of an active ingredient in the oral cavity, a body orifice or a body cavity, wherein the dosage form consists of a matrix comprising one or more water-soluble polymers as base substances and containing at least one active ingredient, the dosage form being characterised by the presence of spaces or cavities in the polymer matrix, the contents of which differ from the matrix in terms of their state of aggregation.

[0005] Patent document 2 refers to a dosage form for application to the skin or mucous membranes, comprising a carrier matrix and at least one active substance, characterized in that the carrier matrix has a plurality of particles having open pores or containing capillary spaces, said particles functioning as active substance reservoirs and containing at least one active substance.

[0006] Patent document 3 describes functional composite particles for the oral care sector, more particularly for toothpastes and mouthwashes, which are charged with active ingredients that ensure a long-term antibacterial or antimicrobial effect in the oral cavity, thus reducing the formation of plaque and bad breath. The invention further relates to a process for producing these composite particles and to their use for producing oral hygiene products.

[0007] US Patent No. 5,399,633 is directed to water-soluble pressure-sensitive adhesives comprising water-soluble polymers that are made tacky at room temperature by the addition of a water-soluble plasticizer that is miscible with the polymer. Suitable polymers are solid at room temperature; and have hydrophilicity as measured by water uptake of greater than about 25 weight percent; they are liquid at room temperature and have a boiling point greater than about 80° C. The adhesives according to the invention may be conveniently provided in dry film form. The preferred water-soluble pressure-sensitive adhesives of the invention are disclosed as adhering to both mucosal surfaces and to a variety of materials that may form part of devices or prostheses that are retained within body cavities that contain mucosal membranes.

[0008] US Patent No. 5,399,663 relates to both bioadhesive and bioerodible confectionery formulations and methods of making and using same, more specifically, the invention provides a delivery system that releases flavors, sweeteners, cooling agents, active ingredients, etc., to the consumer over an extended period of time. Additionally, these confectionery products may also provide a forum for masking the notes and bitterness of drugs or other active ingredients to the consumer.

[0009] Patent document 6 claims a film-like dosage form for transmucosal administration of active substances to the human or animal body. The dosage form is characterized in that the pH value of the base intended for the preparation of the dosage form is adapted or approximated to the physiological pH value of the mucous membrane to which the dosage form is applied, the base being composed of a solvent or a mixture of solvents, at least one matrix-forming polymer and at least one active substance. The invention further comprises a method for the preparation of such a formulation and a method for its use for dosage forms, in particular for medicamentously active substances, such that irritation of the mucous membrane is reduced or prevented when the dosage form obtained is used.

[0010] Patent Document 7 discloses an oral delivery device comprising an adhesive polymer matrix, nanoparticles dispersed therein, and an impermeable backing layer, in which an active substance is loaded on the nanoparticles. The oral administration device should be placed on the mucus layer and adhere to the oral epithelium by mucoadhesion, so that the nanoparticles can penetrate the mucosa and release the loaded active substance in a controlled manner. It discloses that the method for producing the nanoparticles is carried out in a solution containing the active substance and the corresponding polymer.

[0011] US Patent No. 5,399,633 discloses a pharmaceutical dosage form comprising an adhesive layer, a water-insoluble layer and an intermediate layer carrying an active substance, the active substance being in micro- and / or nano-structured form, wherein the active substance is incorporated in the intermediate layer in the form of a suspension or emulsion by controlled dissolution. The mucoadhesion of the dosage form has been evaluated by measuring the tensile force required to separate the dosage film from the simulated gastric mucosa using a Texture Analyser.

[0012] Patent Document 9 relates to a direct compression formulation produced by blending an adhesive polymer, a pharmacoactive substance, a disintegrant and other ingredients, and then compressing the resulting blend. The resulting compressed formulation can be further made into an oral solid formulation. It is disclosed that the application of this dosage form can promote the absorption of the active substance through the oral mucosa and reduce the intake of the active substance.

[0013] Patent Document 10 discloses an intraoral disintegrable film made of an alkaline substance, which disintegrates in the oral cavity within 1-10 minutes and can adhere to the buccal mucosa. It discloses that the adhesiveness of the film was tested with a tensile strength tester.

[0014] US Patent No. 5,999,363 relates to a transmucosal disc containing two compartments for administering an active substance, preferably the active substance being in the inner compartment and the adhesive being in the outer compartment. During application, the partial inner compartment and the partial outer compartment adhere to the mucosa to deliver the active substance through the buccal mucosa. It is disclosed that after the desired effect of the active substance has been achieved, the disc can be easily peeled off.

[0015] US Pat. No. 5,399,633 relates to adhesive active compositions capable of delivering active substances in the oral cavity and corresponding adhesive dosage forms, in particular orodispersible tablets for delivering probiotic substances. [Prior art documents] [Patent documents]

[0016] [Patent Document 1] International Publication No. 2002-002085

[0017] [Patent Document 2] International Publication No. 2003-011247

[0018] [Patent Document 3] European Publication No. 2347796

[0019] [Patent Document 4] U.S. Patent No. 5,700,478

[0020] [Patent Document 5] US Publication No. 2004-0156794

[0021] [Patent Document 6] US Publication No. 2006-0182786

[0022] [Patent Document 7] US Publication No. 2014-0234212

[0023] [Patent Document 8] US Publication No. 2013-0337022

[0024] [Patent Document 9] US Publication No. 2011-0028431

[0025] [Patent Document 10] US Publication No. 2010-0063110

[0026] [Patent Document 11] US Publication No. 2009-0110717

[0027] [Patent Document 12] US Publication No. 2017-071988 Summary of the Invention [Problem to be solved by the invention]

[0028] The object of the present invention is therefore to provide new adhesive compositions with higher strength and / or longer duration and / or improved performance such as combating malodour when in contact with human mucosa, to identify suitable carriers for active agents, particularly aroma molecules used in oral care such as flavours, fragrances etc., and physiological cooling / warming agents. [Means for solving the problem]

[0029] A first object of the present invention refers to a solid adhesive composition comprising or consisting of: (a) at least one active agent, preferably at least one aroma or flavor molecule; (b) at least one carrier; and (c) at least one adhesive polymer; Here, the support is selected from the group consisting of silicon dioxide, silica gel and silicates.

[0030] It has surprisingly been found that silicon dioxide, silicates, and especially silica, are suitable as carriers for certain active agents, ensuring on the one hand long-term storage stability and on the other hand easy delivery to the mucous membranes. [Brief description of the drawings]

[0031] [Figure 1] FIG. 1 is an explanatory diagram showing an adhesive (mucoadhesion) test. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0032] solid adhesive composition The active agents forming component (a) of the composition according to the invention represent agents typically used in oral care formulations which provoke a sensation when in contact with the mucous membrane, these agents are typically selected from the group consisting of flavors, fragrances, physiological cooling agents, physiological warming agents and mixtures thereof.

[0033] Aroma and Flavor Compounds Suitable aromas and flavors may be selected from synthetic flavor liquids and / or oils derived from plant leaves, flowers, fruits, etc., and combinations thereof. Exemplary flavor liquids include artificial, natural or nature-identical flavors such as eucalyptus, lemon, orange, banana, grape, lime, apricot and grapefruit oils and fruit essences including apple, strawberry, cherry, orange, pineapple, etc., flavors derived from beans and nuts such as coffee, cocoa, cola, peanut, almond, etc., and root-derived flavors such as licorice or ginger.

[0034] The flavouring agents are preferably selected from the following group: essential oils and extracts, tinctures and balsams, such as anise oil, basil oil, bergamot oil, bitter almond oil, camphor oil, citronella oil, lemon oil, eucalyptus citriodora oil, eucalyptus oil, fennel oil, grapefruit oil, chamomile oil, spearmint oil, caraway oil, lime oil, mandarin oil, nutmeg oil, myrrh oil, clove oil, clove flower oil, orange oil, oregano oil, parsley (seed) oil, peppermint oil, rosemary oil, sage oil (clary sage, Dalmatian or Spanish sage oil), star anise oil, thyme oil, vanilla extract, juniper oil (especially juniper berry oil), wintergreen oil, cinnamon leaf oil, cinnamon bark oil, and fractions thereof or components isolated therefrom.

[0035] It is particularly advantageous if the flavour composition according to the invention comprises at least one flavouring, preferably two, three, four, five, six, seven, eight or more flavourings, selected from the following group: Menthol (preferably L-menthol and / or racemic menthol), anethole, anisole, anisaldehyde, anisyl alcohol, (racemic) neomenthol, eucalyptol (1,8-cineole), menthone (preferably L-menthone), isomenthone (preferably D-isomenthone), isopulegol, menthyl acetate (preferably L-menthyl acetate), menthyl propionate, carvone (preferably (-)-carvone, optionally with a spare as a component of mint oil), methyl salicylate (optionally as a component of wintergreen oil), eugenol acetate, isoeugenol methyl ether, β-homocyclocitral, eugenol, isobutyraldehyde, 3-octanol, dimethyl sulfide, hexanol, hexanal, trans-2-hexenal, cis-3-hexenol, terpinenol-4, piperitone, linalool, 8-ocimenyl acetate, isoamyl alcohol, isobutaldehyde, α-pinene, β-pinene, limonene (preferably D-limonene, optionally as a component of an essential oil), piperitone, trans-sabinene hydrate, menthofuran, caryophyllene, germacrene D, cinnamaldehyde, mint lactone, thymol, gamma-octalactone, gamma-nonalactone, gamma-decalactone, (1,3E,5Z)-undecatriene, 2-butanone, ethyl formate, 3-octyl acetate, isoamyl isovalerate, cis- and trans-carbyl acetate. , p-cymol, damascone, cis-rose oxide, trans-rose oxide, fenchol, acetaldehyde diethyl, 1-ethoxyethyl acetate, cis-4-heptenal, cis-jasmone, methyl dihydrojasmonate, 2'-hydroxypropiophenone, menthyl methyl ether, myrtenyl acetate, 2-phenylethyl alcohol, 2-phenylethyl isobutyrate, 2-phenylethyl isovalerate, geraniol, nerol, viridiflorol.

[0036] Particularly preferred aroma or flavor compounds include menthol, cineole, eugenol, thymol, cinnamaldehyde, peppermint oil, spearmint oil, eucalyptus oil, thyme oil, cinnamon oil, clove oil, spruce needle oil, fennel oil, sage oil, anise seed oil, star anise oil, chamomile oil, caraway oil, and mixtures thereof.

[0037] Fragrance Fragrances can be used as single components or in the form of more or less complex mixtures. They can be obtained from natural sources or prepared by organic synthesis.

[0038] Natural fragrances include extracts of flowers (lily, lavender, rose, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (anise, coriander, caraway, juniper), fruit peels (bergamot, lemon, orange), roots (nutmeg, angelica, celery, cardamom, costus, iris, calmus), woods (pinewood, sandalwood, guaiacwood, cedarwood, rosewood), herbs and grasses (tarragon, lemongrass, sage, thyme), needles and branches (spruce, fir, pine, dwarf pine), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). Animal sources such as civet and beaver can also be used.

[0039] Synthetic fragrances typically represent aldehydes, ketones, alcohols, ethers, esters, hydrocarbons and mixtures thereof. The following are non-limiting examples of these types of fragrances:

[0040] aldehyde. Examples of suitable fragrances exhibiting aldehyde structures include: Melonal, Tripral, Ligustral, Adoxal, Anisaldehyde, Cymal, Ethyl Vanillin, Florhydral, Floralzone, Helional, Heliotropin, Hydroxycitronellal, Coabon, Lauric aldehyde, Canthoxal, Lyral, Lyrial, Adoxal, Anisaldehyde, Coumarl, Methylnonylacetaldehyde, Citronellal, Citronellyloxyacetaldehyde, Cyclamen aldehyde, Bourjonal, p-tert.-Bucinal, Phenylacetaldehyde, Undecylenaldehyde, Vanillin; 2,6,10-Tet Trimethyl-9-undecenal, 3-dodecen-1-al, α-n-amyldimethaldehyde, 4-methoxy-benzaldehyde, benzaldehyde, 3-(4-tert-butylphenyl)-propanal, 2-methyl-3-(para-methoxy-phenylpropanal), 2-methyl-4-(2,6,6-trimethyl-2(1)-cyclohexen-1-yl)butanal, 3-phenyl-2-propenal, cis- / trans-3,7-dimethyl-2,6-octadien-I-al, 3,7-dimethyl-6-octen-I-al, [(3,7-dimethyl-6-octenyl)- [xy]-Cetaldehyde, 4-isopropylbenzaldehyde, 1,2,3,4,5,6,7,8-octahydro-8,8-dimethyl-2-naphthaldehyde, 2,4-dimethyl-3-cyclohexene-1-carboxaldehyde, 2-methyl-3-(isopropyl-phenyl)propanal, decyl aldehyde, 2,6-dimethyl-5-heptenal; 4-(tricyclo[5.2.1.0(2,6)]-decylidene-8)-butanal;octahydro-4,7-methano-1H-indenecarboxaldehyde;3-ethoxy-4-hydroxybenzaldehyde, para-ethyl-α,α-dimethylhydrocinnamaldehyde, α-methyl-3,4-(methylenedioxy)-hydrocinnamaldehyde, 3,4-methylenedioxybenzaldehyde, α-n-hexyl-cinnamaldehyde, m-cymene-7-carboxaldehyde, α-methylphenylacetaldehyde, 7-hydroxy-3,7-dimethyloctanal, undecenal, 2,4,6-trimethyl-3-cyclohexene-1-carboxaldehyde, 4-(3)(4-methyl-3-pentenyl)-3-cyclohexene-carboxaldehyde,. 1-Dodecanal, 2,4-Dimethyl-cyclohexene-3-carboxaldehyde, 4-(4-hydroxy-4-methylpentyl)-3-cyclohexene-1-carboxyl-aldehyde, 7-Methoxy-3,7-dimethyloctan-1-al, 2-Methylundecanal, 2-Methyldecanal, 1-Nonanal, 1-Octanal, 2,6,10-Trimethyl-5,9-undecadienal, 2 -Methyl-3-(4-tertbutyl)propanal, 3-(4-ethylphenyl)-2,2-dimethylpropanal, 3-(4-methoxyphenyl)-2-methylpropanal, methylnonylacetaldehyde, 2-phenylpropan-1-al, 3-phenylpropan-2-en-1-al, 3-phenyl-2-pentylprop-2-en-1-al, 3-phenyl-2-hexylprop-2-ene aldehyde, 3-(4-isopropylphenyl)-2-methylpropan-1-al, 3-(4-ethylphenyl)-2,2-dimethylpropan-1-al, 3-(4-tert-butylphenyl)-2-methyl-propanal, 3-(3,4-methylenedioxyphenyl)-2-methylpropan-1-al, 3-(4-ethylphenyl)-2,2-dimethylpropanal, 3-(3-isopropylphenyl)-butan-1-al, 2,6-dimethylhept-5-en-1-al, dihydrodimethyaldehyde, 1-methyl-4-(4-methyl-3-pentenyl)-3-cyclohexene-1-carboxaldehyde, 5- or 6-methoxyhexahydro-4,7-methanoindan-1 or 2-carboxaldehyde, 3,7-dimethyloctan-1-al, 1-undecanal, 10-undecen-1-al, 4-Hydroxy-3-methoxybenzalaldehyde, 1-methyl-3-(4-methylpentyl)-3-cyclohexene-carboxaldehyde, 7-hydroxy-3,7-dimethyl-octanal; trans-4-decenal, 2,6-nonadienal, p-tolylacetaldehyde; 4-methylphenylacetaldehyde, 2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2-butenal, o-methoxydimethaldehyde, 3,5,6-trimethyl-3-cyclohexene-carboxaldehyde, 3,7-dimethyl-2-methylene-6-octenal, phenoxyacetaldehyde;5,9-Dimethyl-4,8-decadienal, Peony aldehyde (6,10-dimethyl-3-oxa-5,9-undecadien-1-al), Hexahydro-4,7-methanoindan-1-carboxaldehyde, Octanal, 2-Methyloctanal, α-Methyl-4-(I-methylethyl)benzene-acetaldehyde, 6,6-Dimethyl-2-norpinen-2-propionaldehyde, p-Methylphenoxyacetaldehyde, 2-Methyl-3-phenyl-2-propen-1-al, 3,5,5-Trimethylhexanal, Hexahydro-8,8-dimethyl-2-naphthaldehyde, 3-Propyl-bicyclo [2.2.1]-hept-5-ene-2-carbaldehyde, 9-decenal, 3-methyl-5-phenyl-1-pentanal, methylnonylacetaldehyde, 1-p-menthen-q-carboxaldehyde, citral or mixtures thereof, lylylcitral, 1-decanal, n-undecanal, n-dodecanal, chlorohydral, 2,4-dimethyl-3-cyclohexene-1-carboxaldehyde, 4-methoxybenzaldehyde, 3-methoxy-4-hydroxy-benzaldehyde, 3-ethoxy-4-hydroxybenzaldehyde, 3,4-methylenedioxybenzaldehyde and mixtures thereof;

[0041] As mentioned above, the ketones or the aldehydes may represent aliphatic, alicyclic, aromatic, ethylenically unsaturated structures, or mixtures of these elements. The constituents may also contain heteroatoms or represent polycyclic structures. Suitable substituents for all these structures are hydroxyl and / or amino groups. Other fragrances are summarized in the following books: Steffen Arctander "Published 1960 and 1969 respectively, Reprinted2000 ISBN: Aroma Chemicals Vol. 1: 0-931710-37-5, Aroma Chemicals Vol. 2: 0-931710-38-3" which are incorporated herein by reference.

[0042] Ketones. Examples of suitable fragrances exhibiting a ketone structure include: Bucoxime, Isojasmone, Methyl-β-naphthyl ketone, Mossuindanone, Tonalide / Mossuplus, α-damascone, β-damascone, δ-damascone, Isodamascone, Damascenone, Damarose, Methyl dihydrojasmonate, Menthone, Carvone, Camphor, Fenchone, α-lonene, β-ionone, Dihydro-β-ionone, γ-methylionone, Fluramone, Dihydrojasmone, cis-jasmone, Iso-E-Super, Methyl cedrenyl ketone or Methyl cedrylone, Acetophenone, Methylacetophenone, p-methoxyacetophenone, Methyl-β-naphthyl ketone, Bet-methyl-ionone, benzylacetone, benzophenone, p-hydroxyphenylbutanone, celery ketone or livescone, 6-isopropyl-deca-hydro-2-naphthone, dimethyloctenone, frescom, 4-(I-ethoxyvinyl)-3,3,5,5,-tetramethylcyclohexanone, methylheptenone, 2-(2-(4-methyl-3-cyclohexen-1-yl)propyl)-cyclopentanone, 1-(p-menthen-6(2)-yl)-1-propanone, 4-(4-hydroxy-3-methoxyphenyl)-2-butanone, 2-acetyl-3,3-dimethyl-norbornane, 6,7-dihydro-1,1,2,3,3 -pentamethyl-4(5H)-indanone, 4-damascol, dalcinyl or cassion, gerson, hexalone, isocyclomone E, methyl cyclocitron, methyl lavander ketone, oribone, p-tert-butylcyclohexanone, verdon, delphon, muscone, neobutenone, plicatone, belotone, 2,4,4,7-tetramethyl-oct-6-en-3-one, tetramelane, hedione and mixtures thereof. Preferred ketones are selected from the group comprising α-damascone, δ-damascone, iso-damascone, carvone, γ-methylionone, Iso-E-Super, 2,4,4,7-tetramethyl-oct-6-en-3-one, benzylacetone, β-damascone, damascenone, methyl dihydrojasmonate, cedrylone methyl, hedione and mixtures thereof.

[0043] alcohol. Suitable perfume alcohols include, for example, 10-undecen-1-ol, 2,6-dimethylheptan-2-ol, 2-methylbutanol, 2-methylpentanol, 2-phenoxyethanol, 2-phenylpropanol, 2-tert-butylcyclohexanol, 3,5,5-trimethylcyclohexanol, 3-hexanol, 3-methyl-5-phenylpentanol, 3-octanol, 1-octen-3-ol, 3-phenylpropanol, 4-heptenol, 4-isopropylcyclohexanol, 4-tert-butylcyclohexanol, 6,8-dimethyl-2-nonanol, 6-nonen-1-ol, 9-decen-1-ol, α-methylbenzyl alcohol, α-terpineol, amyl salicylate, benzyl alcohol, benzyl salicylate, β-terpineol, butyrospermum parkii, butyl salicylate ... These include, but are not limited to, citronellol, cyclohexyl salicylate, decanol, dihydromyrcenol, dimethylbenzyl carbinol, dimethylheptanol, dimethyloctanol, ethyl salicylate, ethyl vanillin, anethole, eugenol, geraniol, heptanol, hexyl salicylate, isoborneol, isoeugenol, isopulegol, linalool, menthol, myrtenol, n-hexanol, nerol, nonanol, octanol, paramenthan-7-ol, phenylethyl alcohol, phenol, phenyl salicylate, tetrahydrogeraniol, tetrahydrolinalool, thymol, trans-2-cia-6-nonadienol, trans-2-nonen-1-ol, trans-2-octenol, undecanol, vanillin, cinnamon alcohol and mixtures thereof.

[0044] ester. Examples of suitable fragrances exhibiting an ester structure include benzyl acetate, phenoxyisobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate (DMBCA), phenylethyl acetate, benzyl acetate, ethylmethylphenylglycinate, allylcyclohexylpropionate, styralylpropionate, benzyl salicylate, cyclohexyl salicylate, flormat, mersat, and jasmaciculata, and mixtures thereof.

[0045] ether. Examples of suitable fragrances exhibiting an ether structure include benzyl ethyl ether or ambroxan.

[0046] Hydrocarbons. Examples of suitable fragrances representing hydrocarbons include terpenes, such as limonene and pinene.

[0047] Physiological Cooling and Warming Agents The physiological cooling agent is preferably selected from the following list: Menthol and menthol derivatives (e.g., L-menthol, D-menthol, racemic menthol, isomenthol, neoisomenthol, neomenthol), menthyl ethers (e.g., (I-menthoxy)-1,2-propanediol, (L-menthoxy)-2-methyl-1,2-propanediol), menthone glyceryl acetal. Menthyl glyceryl ketal or a mixture of both, menthyl esters (e.g. menthyl formate, menthyl hydroxyisobutyrate, menthyl lactate, L-menthyl-L-lactate, L-menthyl-D-lactate, menthyl-(2-methoxy)acetate, menthyl-(2-methoxyethoxy)acetate, menthyl pyroglutamate, etc.), menthyl carbonates (e.g. menthyl propylene glycol carbonate, menthyl ethylene glycol carbonate, menthyl glycerol carbonate or mixtures thereof), semi-esters of menthol with dicarboxylic acids or their derivatives (e.g. mono-menthyl succinate, mono-menthyl glutarate, mono-menthyl malonate).Monomenthyl malonate, O-menthyl succinate-N,N-(dimethyl)amide, O-menthyl succinate amide), menthane carboxylic acid amide (in this case, menthane carboxylic acid-N-ethylamide [WS3] or Nα-(menthane carbonyl) glycine ethyl ester [WS5], U.S. Pat. 4,150,052), menthanecarboxylic acid-N-(4-cyanophenyl)amide or menthanecarboxylic acid-N-(4-cyanomethylphenyl)amide as described in WO2005049553A1, menthone and menthone derivatives (e.g. L-menthone glycerol ketal), 2,3-dimethyl-2-(2-propyl)-butyric acid derivatives (e.g. 2.3-dimethyl-2-(2-propyl)-butyric acid-N-methylamide [WS23]), isopulegol or its esters (I-(-)-isopulegol, I-(-)-isopulegol acetic acid), menthane derivatives (e.g. p-menthane-3,8-diol), cubebol or synthetic or synthetic compounds including cubebol are natural mixtures, pyrrolidone derivatives of cycloalkyldione derivatives (e.g. 3-methyl-2(1-pyrrolidinyl)-2-cyclopenten-1-one) or tetrahydropyrimidin-2-ones (e.g. isirine or related compounds described in WO 2004 / 026840), further carboxamides (e.g. N-(2-(pyridin-2-yl)ethyl)-3-p-menthanecarboxamide or related compounds), (1R,2S,5R)-N-(4-methoxyphenyl)-5-methyl-2-(1-isopropyl)cyclohexanecarboxamide [WS12], oxamates (preferably those described in EP 2033688 A2) and [(1R,2S,5R)-5-methyl-cyclohexyl]2-(ethylamino)-2-oxoacetic acid (X Cool).

[0048] The physiological warming agent may be selected from the group consisting of capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin, homodihydrocapsaicin nonivamide, and chili pepper extract.

[0049] Carrier The carrier for the above defined oral active agent forming component (b) is selected from silicon dioxide, silica gel and silicates. In a first preferred embodiment, the carrier is silica gel, which is an amorphous and porous form of silicon dioxide (silica) consisting of an irregular three-dimensional framework of alternating silicon and oxygen atoms with nanometer-sized gaps and pores. The gaps may contain a liquid such as water or may be filled with gas or vacuum. In the latter case, it is more appropriate to call it a silica xerogel. Silica xerogel, with an average pore size of 2.4 nanometers, has a high affinity for water molecules and is widely used as a desiccant. It is hard and translucent, but is rather soft compared to bulk silica glass or quartz, and remains hard even when saturated with water. Silica xerogel is usually commercialized as coarse granules or beads with a diameter of a few millimeters.

[0050] Particularly preferred are the products commercialized under the SIDENT™ brand available from Evonik. This refers to a group of precipitated silicas specially developed for toothpaste applications. For example, SIDENT™ 8, 9 or 22s represent abrasive or thickening silicas with high hardness and low thickening properties for the formulation of toothpaste with improved cleaning efficiency. This product allows the formulation of transparent toothpaste. Alternative products are available under the trade names SYLOID™ (e.g. SYLOID™ FP244, Grace), AEROSIL™ or AEROPERL™, e.g. AEROPERL™ 300 (Evonik), which consists of mesoporous SiO2 granules.

[0051] All of these products exhibit particle sizes ranging from about 3 to about 60 μm, pore volumes ranging from about 1 to about 3 ml / g, pore diameters ranging from about 15 to 60 nm, and surface areas ranging from about 200 to about 500 m2 / g.

[0052] Also useful are silicates, particularly alumosilicates, which are typically used as supports for metal catalysts. In the process of the present invention, suitable silicates share the general formula [SiO(4-2x)-4-x]n, where 0≦x<2. This family includes orthosilicates SiO4-4 (x=0), metasilicates SiO2-3 (x=1) and pyrosilicates SiO6-7 (x=0.5, n=2). This name is also used for salts of the anions, such as sodium metasilicate, or esters containing the corresponding chemical group, such as tetramethylorthosilicate. Suitable alumosilicates follow the formula Al2O3*SiO2, with silica content in the range of 50-75% by weight.

[0053] Adhesive Polymer "Adhesive / mucoadhesive" refers to the property of a substance having the ability to adhere to the mucous membrane of the human body. In the present invention, the adhesive polymer forming component (c) is preferably a hydrophilic polymer or a natural gum. Examples of preferred hydrophilic polymers include hydroxyalkylcellulose-type cellulose-based polymers such as hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, ethyl hydroxyethyl cellulose, carboxymethyl cellulose and salts thereof, and mixtures of two or more of these; vinyl polymers such as polyvinyl acetate, polyvinyl alcohol, and polyvinylpyrrolidone; and acrylic acid polymers and copolymers such as polyacrylic acid, polymethacrylic acid and salts thereof, and polycarbophil. Natural gums are polysaccharides of natural origin. Some examples of natural gums are carrageenan, konjac, sodium and calcium alginate, agarose, guar, pectin, tragacanth, acacia, arabic, dextran, gellan, xanthane, scleroglucan, hyaluronic acid, chitosan, fenugreek, locust bean gum, and the like. Also, combinations of the above adhesive polymers may be employed. Other adhesive polymers or combinations of adhesive polymers may also be used.

[0054] The most preferred adhesive polymers according to the present invention are selected from the group consisting of polyacrylic acid, such as Carbopol™ 971P NF, hypomellose, such as Metolose™ 65SH50, or hydroxypropyl methylcellulose (HPMC), and chitosan.

[0055] composition Preferably, the active agent is incorporated into the carrier, and the carrier is coated with an adhesive polymer. Typically, the carrier is loaded with about 1-about 50% by weight, preferably about 2-about 15% by weight, more particularly about 5-about 10% by weight of the active agent calculated on the carrier. The loading depends on the individual loading capacity of the specific carrier.

[0056] Once the carrier is loaded, it is coated with about 1 to about 25 weight percent, preferably about 3 to about 15 weight percent, and more particularly about 5 to about 10 weight percent of the adhesive polymer calculated on the carrier.

[0057] Manufacturing Process Another object of the invention is a first process for producing a solid adhesive composition (the so-called wet process), comprising or consisting of the following steps: (i) providing at least one active agent; (ii) providing at least one support selected from the group consisting of silicon dioxide, silica gel, silica and silicates; and (iii) providing at least one adhesive polymer; (iv) supporting the active agent on the carrier by any of the following methods: (iv-a) contacting the support with an active agent, optionally dissolved in a solvent, followed by removal of the solvent to obtain the supported support; or (iv-b) contacting the support with a solid activator and then melting the activator to obtain a supported support; (v) coating the supported carrier by contacting the product of step (iv) with a suspension of at least one adhesive polymer in water or a lipophilic solvent.

[0058] During the "wet process", the support is typically wetted or impregnated with a solution or dispersion of the active agent (which may be solid or liquid) in a suitable solvent, such as water, ethanol or an oil. This step can be carried out at room temperature, preferably with vigorous stirring. The solvent is then separated by filtration or, preferably, evaporation.

[0059] The next step is to coat the supported carrier with a polymer. Usually, the carrier is placed in a mixer and a solution or dispersion of the polymer in a suitable solvent is added dropwise under vigorous stirring. The solvent can be water, but lipids have been found to be superior in terms of coating stability. Therefore, the preferred solvents for the coating material are triglycerides, such as triacetin or sunflower oil, or the active agents themselves (preferably lipophilic fragrances or flavors), provided that they present a lipophilic liquid.

[0060] Another object of the invention refers to a second process for producing a solid adhesive composition, the so-called dry / hot melt process, which comprises or consists of the following steps: (i) providing at least one active agent; (ii) providing at least one support selected from the group consisting of silicon dioxide, silica, silica gel and silicates; and (iii) providing at least one adhesive polymer; (iv) supporting the active agent on the carrier by any of the following methods: (iv-a) contacting the support with an active agent dissolved in a solvent, followed by removal of the solvent to obtain the supported support; or (iv-b) contacting the support with a solid activator and then fusing the two solids to obtain a supported support; (v) coating the loaded carrier by contacting the product of step (iv) with at least one adhesive polymer in a substance and mixing both components under high shear.

[0061] The second process differs from the first in that the coating is done substantially ("powder coating"). This means that the polymer is not dissolved or dispersed in a solvent, but added directly to the carrier. The coating is done by vigorous mixing of the two components under high shear, for example using a high shear mixer, preferably in the presence of another non-sticky polymer with a melting point of about 30 to about 60°C, such as a solid polyglycol ether (e.g. PEG-1000). The second polymer is added in an amount of about 5 to about 25% by weight - calculated on the mixture. In this alternative, the high shear mixing is carried out at a temperature above the melting point of the second polymer.

[0062] Oral composition Another object of the present invention refers to an oral formulation comprising the adhesive composition as defined above, preferably in an amount of about 0.1 to about 10% by weight, more preferably about 1 to about 8% by weight, most preferably about 2 to about 5% by weight.

[0063] The oral formulation may be selected from the group consisting of (hard-boiled) candies, compressed tablets, chewing gums, and toothpastes, and more particularly from the following: - Toothpaste, - Toothpaste tablets, - Tooth cleaning foam, - semi-solid preparations for use in the oral cavity, - sublingual and buccal tablets, - adhesive preparations, - molten film, - Tablets (coated and uncoated, modified and uncoated release, chewable tablets, lyophilized for ingestion), - sugar tablets (coated or uncoated, modified release or uncoated), - Capsules (hard or soft gelatin capsules, modified or non-modified release); - Granules (with or without modified release), and - Powders (modified and non-modified release).

[0064] The preparation and composition of the oral composition is described below.

[0065] candy According to the present invention, the preferred candy is the so-called hard-boiled candy. Its base is usually prepared from a mixture of sugar and other carbohydrates kept in an amorphous or glassy state. This form can be considered as a solid syrup of sugars, generally having a water content of up to about 4.5% by weight, with about 0.5-about 2.5% being preferred, and about 1.0-about 1.5% being most preferred, based on the weight of the candy base. Such materials usually contain up to 65% by weight corn syrup, up to 80% by weight sugar, and 0.1-5.0% by weight water. Generally, the ratio of sugar (or other sweetener suitable for candy formulations) to corn syrup is in the range of about 70:25-about 45:55, with about 60:40 being preferred. The syrup component is generally prepared from corn syrup that is high in fructose, but may contain other materials. Further ingredients such as flavors, sweeteners, acidulants, and colorants may also be added.

[0066] The hard-boiled candy base may also be prepared from non-fermentable sugars such as sorbitol, mannitol, xylitol, maltitol, hydrogenated starch hydrolysates, hydrogenated corn syrup and mixtures thereof. The candy base may contain up to about 95% by weight sorbitol, mixtures of sorbitol and mannitol in ratios of about 7.5-2.5 to about 9.5-0.5, and hydrogenated corn syrup up to about 55 percent by weight of the syrup component.

[0067] Compressed tablets In accordance with the present invention, the oral composition may represent a compressed tablet that typically contains liquid flavor in an amount of about 0.1 to about 0.6% by weight, preferably about 0.5% by weight.

[0068] Chewing gum Chewing gum typically consists of a water insoluble base component, a water soluble component, and additives that provide, for example, a particular flavor.

[0069] The water-insoluble base, also called "gum base", is usually composed of natural or synthetic elastomers, resins, fats and oils, plasticizers, fillers, softeners, dyes and optionally waxes. The base usually constitutes 5-95% by weight, preferably 10-50% by weight, more particularly 20-35% by weight of the total composition. In one typical embodiment of the invention, the base comprises 20-60% by weight of synthetic elastomers, 0-30% by weight of natural elastomers, 5-55% by weight of plasticizers, 4-35% by weight of fillers, 5-35% by weight of softeners and small amounts of additives such as pigments, antioxidants, etc., which are soluble in water even in small amounts.

[0070] Suitable synthetic elastomers are, for example, polyisobutylene, isobutylene / isoprene copolymers ("butyl elastomers") with an average molecular weight (measured by GPC) of 10,000-100,000, preferably 50,000-80,000, styrene / butadiene copolymers (styrene:butadiene ratio, for example, 1:3-3:1) with an average molecular weight (measured by GPC) of 2,000-90,000, polyvinyl acetate, polyisoprene, polyethylene, vinyl acetate / laurate copolymers, preferably 10,000-65,000, and mixtures thereof. Examples of suitable natural elastomers are rubbers, such as smoked or liquid latex or guayule, and natural gums, such as jelutong, reticaspi, perillo, sorba, massarandubalata, massarandubalachoko, nispero, rosindimbá, chicle, guttahankang, and mixtures thereof. The choice of synthetic and natural elastomers and their mixing ratio depends essentially on whether the chewing gum (bubble gum) is intended to generate bubbles or not. Elastomer mixtures containing jelutong, chicle, sorba and massaranjuba are preferably used.

[0071] In most cases, elastomers are too hard or not plastic enough to be processed satisfactorily. It has therefore proven advantageous to use special plasticizers, which of course must also in particular meet all the requirements for acceptability as food additives. In this respect, suitable plasticizers are, inter alia, esters of resin acids, for example esters of lower aliphatic alcohols or polyols with fully or partially hydrogenated, monomeric or oligomeric resin acids. In particular, methyl, glycerol or pentaerythritol esters or mixtures thereof are used for this purpose. Alternatively, terpene resins may be used, which may be derived from α-pinene, β-pinene, δ-limonene or mixtures thereof.

[0072] Suitable fillers or texturizers are magnesium or calcium carbonate, ground pumice, silicates, especially magnesium or aluminum silicate, clay, aluminum oxide, talcum, titanium dioxide, mono-, di- and tricalcium phosphates, and cellulose polymers.

[0073] Suitable softeners or emulsifiers are tallow, hydrogenated tallow, hydrogenated or partially hydrogenated vegetable oils, cocoa butter, partial glycerides, lecithin, triacetin and saturated or unsaturated fatty acids containing 6 to 22, preferably 12 to 18, carbon atoms, and mixtures thereof.

[0074] Suitable dyes and whiteners are, for example, FD&C types, plant and fruit extracts permitted for coloring food, and titanium dioxide. The gum base may also contain wax or be wax-free.

[0075] In addition to the water-insoluble gum base, chewing gum preparations regularly contain water-soluble components, which are formed, for example, by softeners, sweeteners, fillers, flavors, flavor enhancers, emulsifiers, dyes, acidulants, antioxidants, etc., provided that the components have at least adequate solubility in water. Thus, individual components can belong to both the water-insoluble and the water-soluble phases, depending on the water solubility of the particular representative. However, combinations can also be used, for example combinations of water-soluble and water-insoluble emulsifiers, in which case the individual representatives are present in different phases. The water-insoluble components usually constitute 5-95% by weight of the formulation, preferably 20-80% by weight.

[0076] Water-soluble softeners or plasticizers are added to chewing gum compositions to improve chewiness and chewing feel, and are usually present in the mixture in amounts of 0.5-15 weight percent. Typical examples are aqueous solutions of glycerol, lecithin and sorbitol, hydrogenated starch hydrolysates or corn syrup.

[0077] The fillers are particularly suitable for the production of low calorie chewing gum and may be selected, for example, from polydextrose, raffilose, raffilin, fructooligosaccharides (NutraFlora), palatinose oligosaccharides, guar gum hydrolysate (Sun Fiber) and dextrin.

[0078] The chewing gum may furthermore contain adjuvants and additives suitable for example for dental care, more particularly for controlling plaque and gingivitis, such as for example chlorhexidine, CPC or triclosan, pH adjusters (for example buffers or urea), anti-caries agents (for example phosphates or fluorides), substances of biological origin (antibodies, enzymes, caffeine, plant extracts, probiotic bacteria), provided that these substances are food-tolerable and do not interact unfavorably with each other.

[0079] Toothpaste Toothpaste or tooth cream is generally understood as a paste-like formulation of water, thickeners, humectants, abrasives or polishes, surfactants, sweeteners, flavors, deodorants and active agents against oral and dental diseases. Any of the usual abrasives can be used in toothpastes according to the invention, such as chalk, dibasic calcium phosphate, insoluble sodium metaphosphate, aluminum silicate, calcium pyrophosphate, finely divided synthetic resins, silica, aluminum oxide and aluminum oxide trihydrate. Polishes particularly suitable for toothpastes according to the invention are micronized xerogel silica, hydrogel silica, precipitated silica, aluminum oxide trihydrate and micronized alpha-alumina, or mixtures of these polishes. Such polishes are preferably used in an amount of about 15-40% by weight of the toothpaste. Preferred humectants for use in toothpastes according to the invention are low molecular weight polyethylene glycols, glycerol, sorbitol or mixtures thereof in an amount up to about 50% by weight of the toothpaste. Among known thickening agents for use in toothpastes according to the invention, particularly preferred are thickening, particulate gelling silica and non-ionic hydrocolloids, such as hydroxyethylcellulose, hydroxypropyl guar, hydroxyethyl starch, polyvinylpyrrolidone, high molecular weight polyethylene glycols and vegetable gums, such as tragacanth, agaric acid, carrageen moss, gum arabic and xanthan gum. The desired flavor and aroma for the formulation according to the invention can be obtained by adding components (a) and / or (b) and, optionally, (c). It is also advantageous to add caries inhibitors to the oral preparation, for example in the form of an alkali fluoride, an alkali monofluorophosphate or an alkali salt of an organic phosphonic acid. Furthermore, the oral preparation according to the invention may contain other standard auxiliaries, such as dyes, preservatives and opacifiers, such as titanium dioxide.

[0080] additives The oral compositions of the present invention may also contain additional additives, such as sweeteners and vitamins, in amounts of from about 0.001 to about 10% by weight.

[0081] sweetener Suitable sweetening substances include natural sources of these substances (ingredient e5). For example, sweet carbohydrates or sugars (e.g. sucrose (synonymous saccharose), trehalose, lactose, maltose, melizitose, raffinose, palatinose, lactulose, D-fructose, D-glucose, D-galactose, L-rhamnose, D-sorbose, D-mannose, D-tagatose, D-arabinose, L-arabinose, D-ribose, D-glyceraldehyde, maltodextrin) and plant preparations which mainly contain these carbohydrates (e.g. from sugar beet (Beta vulgaris ssp., sugar fraction, sugar syrup, molasses), from sugar cane (Saccharum officinarum ssp., e.g. molasses, sugar syrup), from sugar maple (Acer ssp.), from agave (agave juice), synthetic / enzymatic hydrolysates of starch or sucrose (e.g. invert sugar syrup, high fructose syrup made from corn starch), fruit concentrates (e.g. from apples or pears, apple syrup, pear syrup), sugar alcohols (e.g. erythritol, threitol, arabitol, ribitol, xylitol, sorbitol, mannitol, dulcitol, lactitol), proteins (e.g. miraculin, monellin, lactol, etc. miraculin, monellin, thaumatin, curculin, brazzein), sweeteners (magap, sodium cyclamate, acesulfame K, neohesperidin dihydrochalcone, sodium saccharin, aspartame, super spartame, neotame, alitame, sucralose).Examples of sweeteners include steviosides, rebaudiosides, ragduname, carreram, sucrononate, sucrooctate, monatin, phyllodulcin), certain sweet amino acids (glycine, D-leucine, D-threonine, D-asparagine, D-phenylalanine, D-tryptophan, L-proline), other low molecular weight substances having a sweet taste (e.g. hernandulcin, dihydrochalcone glycosides, glycyrrhizin, ammonium salt of glycyrrhetinic acid or other glycyrrhetinic acid derivatives), licorice extracts (Glycyrrhizza glabra ssp.), Lippia dulcis extracts, Momordica ssp. extracts or individual substances (especially Momordica grosvenori [Luo Han Guo] and the mogrosides obtained therefrom), Hydrangea dulcis or Stevia ssp. (such as Stevia rebaudiana) extracts or individual substances.

[0082] Vitamins In another embodiment of the invention, the composition may contain vitamins (ingredient e1). Vitamins have a variety of biochemical functions. Some have hormone-like functions as regulators of mineral metabolism (e.g. vitamin D) or of cell and tissue growth and differentiation (e.g. some forms of vitamin A). Others function as antioxidants (e.g. vitamin E and possibly vitamin C). Most vitamins (e.g. B vitamins) act as precursors of coenzymes for enzymes, helping them to act as metabolic catalysts. In this role, vitamins may be tightly bound to enzymes as part of a coenzyme family. For example, biotin is part of the enzymes involved in the production of fatty acids. Vitamins may also be less tightly bound to enzyme catalysts as coenzymes. Coenzymes are detachable molecules that serve to transport chemical groups or electrons between molecules. For example, folic acid carries various carbon groups such as methyl, formyl, and methylene groups within cells. While aiding enzyme-substrate reactions in this way is the best-known function of vitamins, other vitamins have important functions as well. In the process of the present invention, suitable vitamins are selected from the group consisting of: - Vitamin A (retinol, retinal, beta-carotene). - Vitamin B1 (thiamine). - Vitamin B2 (riboflavin). - Vitamin B3 (niacin, niacinamide). - Vitamin B5 (Pantothenic Acid) - Vitamin B6 (pyridoxine, pyridoxamine, pyridoxal) - Vitamin B7 (Biotin) - Vitamin B9 (Folic Acid, Folinic Acid) - Vitamin B12 (cyanobalamin, hydroxocobalamin, methylcobalamin). - Vitamin C (ascorbic acid). - Vitamin D (cholecalciferol). - Vitamin E (tocopherol, tocotrienol), and - Vitamin K (phylloquinone, menaquinone).

[0083] Preferred vitamins are ascorbic acid and tocopherol. The vitamins may be present in the food composition in an amount of about 0.001 to about 5% by weight, preferably about 0.5 to about 1% by weight.

[0084] Industrial applicability Another object of the present invention is the use of such adhesive composition for making oral preparations, especially toothpaste.To avoid any ambiguity, all preferred embodiments, ranges, mixtures and applications described above shall also apply to the specific applications. EXAMPLES

[0085] Example 1 to Example 4 Stability of supported carriers Various types of silica were treated with a liquid flavor mixture consisting of anethole, carvone, and eucalyptol in a weight ratio of 60:30:10 ("OPTAMINT™ LIQUID") or a liquid flavor mixture consisting of menthol, thymol, and camphor in a weight ratio of 60:30:10 ("OPTAMINT™ LIQUID") and stored in sealed glass at 20°C, protected from light. On the other hand, a temperature profile was applied in which the samples were heated from -5°C to 40°C, followed by cooling to -5°C in 24 hours. Over a period of 6 months, the amount of flavor remaining in each carrier was measured by high performance liquid chromatography (HPLC). The results are summarized in Table 1. Table 1 Carrier stability test [Table 1]

[0086] Examples 1-3 were carried out using carriers (products 1-3) with flavor loaded to about 100% by weight of the carrier volume. This experiment shows that the loading does not change substantially during storage. Example 4 was carried out using an overloaded carrier (product 4; loading limit: 3.4 weight percent), i.e., about 1.2 weight percent of flavor is not incorporated within the carrier, but is only bound to the outer surface. It was confirmed that when this carrier is stored, only a portion of the flavor attached to the outer surface of the carrier is released.

[0087] Example 5-Example 6 Stability of Coated Substrates - Liquid Coating To coat the carrier loaded with the adhesive polymer, product 2 was placed in a mixer at 20° C. and a 10% by weight suspension of hydroxypropylmethylcellulose (HPMC) in sunflower oil was added dropwise over 2 minutes under rigorous stirring at 400-600 rpm (product 5). After the polymer was added, the solution was stirred for an additional 5 minutes. Another method was to simultaneously load and coat the unloaded carrier by suspending the polymer (HPMC) in Optamint™ liquid flavor (product 6), in which case the procedure was carried out as described for product 5. The coated carrier was again stored in a sealed vial at 20° C. and again following a temperature gradient as in the previous examples, and the polymer content was measured by HPLC over a period of up to 6 months. The results are summarized in Table 2. Table 2 Stability testing of coated supports [Table 2]

[0088] In particular, coating from an oil-containing suspension and the one-step approach of suspending the polymer in liquid flavor resulted in coated carriers with little change in polymer content even after 6 months.

[0089] Example 7-Example 8 Stability of coated substrates - dry and hot melt coating In the first experiment (Product 7), Product 2 was added to a high shear mixer with 3 weight percent HPMC and homogenized at 400, 1,500 and 3,000 rpm for 2 minutes each. In the second experiment (Product 8), Product 2 with 5 weight percent HPMC was again homogenized in a high shear mixer for 5 minutes, first at 400 rpm and then at 1,500 rpm. Next, 10 weight percent PEG-1000 was added and the mixture was heated to 45° C. above the melting point of the polyglycol ether and homogenized at 400 rpm for 5 minutes and then at 1,500 rpm for 25 minutes. The mixture was then slowly cooled to 20° C. with a stirring speed of 1,500 rpm. The coated carriers (Optamint™ loading: 10.39 and 9.52 weight percent, respectively) were again temporarily stored at 20° C. in sealed vials and again stored according to a temperature gradient as in the previous examples, and the polymer content was determined by HPLC for up to 6 months. The results are summarized in Table 3. Table 3 Stability testing of coated supports [Table 3]

[0090] Also, dry high shear mixing and hot melt processing using PEG are promising processes to obtain stable coated carriers.

[0091] Example 9-Example 10 Adhesion (mucoadhesion) test A piece of porcine mucosa with a thickness of about 2 mm and a diameter of about 2.5 cm was prepared and placed on a metal disk in a mucosal adhesion cell. The sample was placed on the mucosa, and its surface was wetted by dripping artificial saliva from a container (AS) at a flow rate of 0.5 ml / min using an HPLC pump (P). The cell and container were placed in the same water bath to ensure the same temperature of 37°C, as shown in Figure 1. The artificial saliva used was prepared according to Matzker / Schreiber 1972 (without CaCl2), and its composition was as shown in Table 4 below. Table 4 artificial saliva [Table 4]

[0092] Optamint™ was recovered from saliva collected after 2, 4, 6, 8, 10, and 12 minutes, and from the mucosa after an additional 12 minutes. Retained carrier was removed from the mucosa with a cotton swab and 1 ml EtOH. The swab was extracted with 5 ml EtOH and analyzed by HPLC. The results are summarized in Table 5. The examples show that the addition of 3-4 weight percent HPMC as a tackifier significantly improves mucoadhesion by 2-3 times compared to the plain carrier (Product 2). Table 5 mucoadhesive [Table 5]

[0093] Example 11-Example 12 Adhesion testing with optimized polymer content Adhesion tests were performed with increasing polymer content using flavor carriers from Product 5 containing 10 weight percent HPMC (Product 9) and Product 8 containing 10 weight percent HPMC as well as 10 weight percent PEG-1000 (Product 10). The results are shown in Table 6. This example shows that the addition of 10 weight percent HPMC as an adhesive significantly increases adhesion by 4-8 times compared to the plain carrier (Product 2). Table 6 Mucoadhesiveness with optimized polymer content [Table 6]

[0094] Example 13-Example 14 Adhesion testing with alternative polymers Additionally, adhesion tests using Carbopol™ and chitosan as alternative polymers instead of HPMC were conducted using flavor carriers from Product 5 containing 10 wt% Carbopol™ 971 P NF (Product 11) and 6 wt% chitosan food grade (Product 12), respectively. The results are shown in Table 7. This example shows that the mucoadhesion was increased by 2 times for Product 12 and 9 times for Product 11 compared to the plain carrier (Product 2). Table 7 Mucoadhesiveness using alternative polymers [Table 7]

[0095] Example 15 to Example 17 Adhesion testing using alternative carriers Additionally, adhesion tests were performed with Sident™ 9 as the carrier. The preparation of the flavor carriers was performed similarly to product 4. Polymer additions were performed with HPMC in 8 wt% sunflower oil (product 13), Carbopol™ in 8 wt% sunflower oil (product 14) and HPMC 10 wt% and PEG-1000 10 wt% (product 15) respectively. The results are shown in Table 8. This example shows a significant increase in adhesion compared to the plain carrier (product 4) by a factor of 2.5 for product 13 and a factor of 4 for product 14. Product 15 only showed a slight increase in adhesion compared to the plain carrier. Table 8 Adhesiveness using alternative polymers [Table 8]

[0096] Example 18-Example 19 Adhesion test using triacetin as a solvent Triacetin was tested as a binder solvent for the polymer instead of sunflower oil and adhesion tests were also performed. Samples were prepared according to Product 9 with 10 weight percent HPMC (Product 16) and Product 11 with 10 weight percent Carbopol™ (Product 17), respectively, but with triacetin instead of sunflower oil as the solvent. The adhesion test results are shown in Table 9. In this example, it can be seen that there is a significant improvement in adhesion compared to the plain carrier (Product 2), by a factor of 4.5 for Product 16 and a factor of 7.5 for Product 17. Table 9 Adhesive with triacetin as a solvent [Table 9]

[0097] Example 20 to Example 23 Long-lasting adhesion For certain carriers, adhesion was measured after 30 and 60 minutes in addition to the 12 minute test. Table 10 shows that the amount of flavor adhered to the mucosa decreases with successive times for all mucosal carriers. However, adhesion to the mucosa of all sticky carriers is much better than that of the plain carrier. Table 10 Long-lasting adhesion [Table 10] JPEG0007641991000011.jpg2564

[0098] Combination example Tables I-III below provide various examples for oral compositions; all amounts are given in weight percent. Table I Chewing gum [Table I] Table II Toothpaste [Table II] Table III Hard Boiled Candy [Table III]

Claims

1. (a) at least one active agent selected from the group consisting of flavors, fragrances, physiological cooling agents, physiological warming agents, and mixtures thereof; (b) at least one carrier; and (c) at least one adhesive polymer selected from the group consisting of polyacrylic acid, polymethacrylic acid, hydroxyalkylmethylcellulose, and chitosan; The carrier is - Particle size is 3-60 μm, Pore ​​volume is 1-3 ml / g; - pore diameter 15-60 nm; - Surface area is 200-500 m ２ / g, A solid adhesive composition, wherein the active agent is incorporated into the carrier, and the carrier is coated with the adhesive polymer.

2. 2. The solid adhesive composition of claim 1, wherein the active agent is selected from the group consisting of anethole, carvone, eucalyptol, menthol, thymol, camphor, and mixtures thereof.

3. 2. The solid adhesive composition of claim 1, wherein the silica is SIDENT™ 8, 9 or 22s, or AEROPERL™ 300.

4. The solid adhesive composition of claim 1, wherein the hydroxyalkyl methylcellulose is hydroxypropyl methylcellulose.

5. 2. The solid adhesive composition of claim 1, wherein said carrier is loaded with 1-15% by weight of said activator, calculated on said carrier.

6. 2. The solid adhesive composition of claim 1, wherein the supported carrier is coated with 1-15% by weight of adhesive carrier, calculated on the supported carrier.

7. (i) providing at least one active agent selected from the group consisting of flavors, fragrances, physiological cooling agents, physiological warming agents, and mixtures thereof; (ii) providing at least one carrier; (iii) providing at least one adhesive polymer selected from the group consisting of polyacrylic acid, polymethacrylic acid, hydroxyalkylmethylcellulose, and chitosan; (iv) supporting the active agent on the carrier by any of the following methods: (iv-a) contacting the support with the active agent dissolved in a solvent and then removing the solvent to obtain the supported support; or (iv-b) contacting the support with a solid activator and then fusing the support with the solid activator to obtain a supported support; (v) coating the supported carrier by contacting the product of step (iv) with a suspension of at least one of said adhesive polymers in water or a lipophilic solvent, The carrier is - Particle size is 3-60 μm, Pore ​​volume is 1-3 ml / g; - pore diameter 15-60 nm; - Surface area is 200-500 m ２ 2. A process for producing a solid adhesive composition, the solid adhesive composition being a silica exhibiting a characteristic of 0.1 g / g.

8. 8. The process of claim 7, wherein the lipophilic solvent is a triglyceride or a liquid lipophilic flavor, fragrance, physiological cooling agent, physiological warming agent, physiological cooling agent or physiological warming agent.

9. (i) providing at least one active agent selected from the group consisting of flavors, fragrances, physiological cooling agents, physiological warming agents, and mixtures thereof; (ii) providing at least one support; (iii) providing at least one adhesive polymer selected from the group consisting of polyacrylic acid, polymethacrylic acid, hydroxyalkylmethylcellulose, and chitosan; (iv) supporting the active agent on the carrier by any of the following methods: (iv-a) contacting the support with an active agent, optionally dissolved in a solvent, followed by removal of the solvent to obtain the supported support; or (iv-b) contacting the support with a solid activator, and then fusing the support and the solid activator to obtain the supported support; (v) contacting the product of step (iv) with at least one said adhesive polymer in a substance and mixing both components under high shear, thereby coating the loaded carrier, The carrier is - Particle size is 3-60 μm, Pore ​​volume is 1-3 ml / g; - pore diameter 15-60 nm; - Surface area is 200-500 m ２ / g of silica. A process for producing a solid adhesive composition.

10. 10. The process of claim 9, wherein step (v) is carried out in the presence of a non-sticky polymer having a melting point of 30-60°C.

11. An oral formulation comprising the solid adhesive composition of claim 1.

12. - Toothpaste, - Toothpaste, - Toothpaste tablets, - Tooth cleaning foam, - semi-solid preparations for use in the oral cavity, - Sublingual and buccal tablets, - adhesive preparations, - molten film, - tablets (coated and uncoated, modified and uncoated release, chewable tablets, lyophilized forms for ingestion); - sugar tablets (coated or uncoated, modified release or uncoated); - Capsules (hard or soft gelatin capsules, modified or non-modified release), - granules (with or without modified release); - Powders (modified and non-modified); - Hard Boiled Candy, and - Chewing gum, 12. The oral formulation of claim 11 selected from the group consisting of:

13. 12. The oral formulation of claim 11 comprising the solid adhesive composition in an amount of 0.1-25% by weight.

14. 13. Use of the solid adhesive composition according to claim 1 for the manufacture of an oral preparation.

15. Use of the solid adhesive composition of claim 14, wherein the oral preparation is a toothpaste.

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