Multi component controlled release system for oral care, food products, nutraceutical, and beverages

Abstract

The present invention relates to an improved controlled release system that can encapsulate different flavors, sensory markers, and active ingredients, or combinations of flavors, sensory markers and various active ingredients and release multiple active ingredients in a consecutive manner, one after the other. The controlled delivery system of the present invention is substantially free-flowing powder formed of solid hydrophobic nanospheres that are encapsulated in a moisture sensitive microspheres. The flavors, and active ingredients encapsulated in the hydrophobic nanospheres, in the water sensitive microsphere, or in both the nano and the microsphere. The flavors and active ingredients encapsulated in the nanospheres can be the same or different from those encapsulated in the microspheres. The encapsulation of different flavors or active agents in the various components of the system, such as nanospheres and microspheres, provides flavor transition (change in flavor character) during the use of the products. The controlled release system of the present invention enhances the stability and bioavailability of wide range of flavors, sensory markers, and other active ingredients, prolong their residence time in the oral cavity, control their release characteristics, and prolong the sensation of flavors and other sensory markers in the mouth to provide long lasting organoleptic perception or long lasting mouthfeel. The invention further relates oral care, food products, and beverages comprising the controlled release system of the present invention.

1 . A multi-component moisture activated controlled release delivery system for delivery to biological surfaces comprising an oral cavity or mucous membranes of various tissues, said system comprising: 
 a plurality of solid nano-particles formed of a hydrophobic material, said hydrophobic material comprises natural wax, synthetic wax, fat, glyceride, fatty acid, fatty acid derivative and mixtures thereof each of said solid nano-particles comprising a core and an effective amount of a first active agent contained therein, said plurality of nano-particles being homogenously dispersed within a moisture sensitive microparticle, said microparticle is formed of a moisture sensitive matrix material and a bioadhesive material surrounding said core or a bioadhesive material within said moisture sensitive matrix material, said moisture-sensitive matrix material comprises a water soluable synthetic polymer, water dispersible synthetic polymer, starch derivative, natural gum, polysacchride, protein, hydrocolloid and mixtures thereof.    
     
     
         2 . canceled.  
     
     
         3 . canceled.  
     
     
         4 . canceled.  
     
     
         5 . canceled.  
     
     
         6 . The system of  claim 1  wherein said water-soluable synthetic polymer is selected from the group consisting of: polyvinyl pyrrolidone, water soluble cellulose, polyvinyl alcohol, ethylene maleic anhydride copolymer, methylvinyl ether maleic anhydride copolymer, acrylic acid copolymers, anionic polymers of methacrylic acid and methacrylate, cationic polymers with dimethyl-aminoethyl ammonium functional groups, polyethylene oxides, water soluble polyamide and polyester and mixtures thereof.  
     
     
         7 . canceled.  
     
     
         8 . canceled.  
     
     
         9 . The system of  claim 1  wherein said bioadhesive material is selected from the group consisting of bioerodible hydrogels, polyhyaluronic acid, casein, gelatin, glutin, polyanhydride, polyacrylic acid, alginate, chitosan, poly(methyl methacrylate), poly(ethyl methacrylate), poly (butyl methacrylate), poly(isobutyl methacrylate), poly(hexl methacrylate), poly(isodecl methacrylate), poly(lauryl methacrylate), poly(phenyl methacrylate), poly(methyl acrylate), poly(isopropyl acrylate), poly(isobutyl acrylate), and poly(octadecl acrylate), poly(fumaric-co-sebacic)acid and mixtures thereof.  
     
     
         10 . The system of  claim 1  wherein said bioadhesive material is a polymer comprising anhydride monomers or oligomers.  
     
     
         11 . The system of  claim 1  wherein said first active agent is a sensory marker of a flavor or cooling agent.  
     
     
         12 . The system of  claim 11  wherein said cooling agent is selected from the group consisting of: menthol, non-volatile menthol analogs, menthyl lactate, menthyl ethoxyacetate, menthone glycerinacetal, 3-1-menthoxypropane-1,2-diol, ethyl 1-menthyl carbonate, (1S,3S,4R)-p-menth-8-en-3-ol, menthyl pyrrolidone carboxylate, N-substituted-p-menthane-3-carboxamide, N-ethyl-p-menthane-3-carboxamide, N,2,3-trimethyl-2-isopropylbutanamide, ketal coolants, 1-menthon-1d-isomenthon glycerin ketal, 3-1-menthoxypropane-1,2-diol, N-ethyl-p-menthane-3-carboxamide, N,2,3-trimethyl-2-isopropylbutanamide, menthyl lactate, menthone glycerinacetal and menthyl ethoxyacetate.  
     
     
         13 . The system of  claim 1  wherein said first active agent is a nutraceutical component selected from the group consisting of: antioxidants, phytochemicals, hormones, vitamins, Vitamin A, Vitamin B1, Vitamin B2, Vitamin B6, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K, pantothenate, folic acid, pro-vitamins, minerals, calcium, selenium, magnesium salts, iron, iron salts, microorganisms, bacteria, lactobacilli, fungi, yeast, prebiotics, probiotics, unsaturated fatty acids, omega-3 fatty acids, mid-chain triglycerides, nutritional supplements, enzymes, amylases, proteases, lipases, pectinases, cellulases, hemicellulases, pentosanases, xylanases, and phytases, pigments, oligopeptides, dipeptides, amino acids and mixtures thereof.  
     
     
         14 . The system of  claim 1  further comprising one or more of an amphoteric surfactant, non-ionic surfactant and cationic surfactant.  
     
     
         15 . The system of  claim 1  wherein said moisture sensitive matrix comprises a second active agent, said second active agent being the same or different as said first active agent, said moisture sensitive matrix material releases said second active agent upon contact with moisture and continuously thereafter for an extended period of time.  
     
     
         16 . The system of  claim 15  wherein said second active agent is a first flavor and said first active agent is a second flavor, said first flavor being different than said second flavor wherein release of said first flavor and said second flavor provides an organoleptic perception of a flavor transition.  
     
     
         17 . The system of  claim 14  wherein said second active agent is a sensory marker of a flavor or cooling agent.  
     
     
         18 . The system of  claim 16  wherein said cooling agent is selected from the group consisting of: menthol, non-volatile menthol analogs, menthyl lactate, menthyl ethoxyacetate, menthone glycerinacetal, 3-1-menthoxypropane-1,2-diol, ethyl 1-menthyl carbonate, (1S,3S,4R)-p-menth-8-en-3-ol, menthyl pyrrolidone carboxylate, N-substituted-p-menthane-3-carboxamide, N-ethyl-p-menthane-3-carboxamide, N,2,3-trimethyl-2-isopropylbutanamide, ketal coolants, 1-menthon-1d-isomenthon glycerin ketal, 3-1-menthoxypropane-1,2-diol, N-ethyl-p-menthane-3-carboxamide, N,2,3-trimethyl-2-isopropylbutanamide, menthyl lactate, menthone glycerinacetal and menthyl ethoxyacetate.  
     
     
         19 . The system of  claim 15  wherein said second active agent is a nutraceutical component selected from the group consisting of: antioxidants, phytochemicals, hormones, vitamins, Vitamin A, Vitamin B1, Vitamin B2, Vitamin B6, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K, pantothenate, folic acid, pro-vitamins, minerals, calcium, selenium, magnesium salts, iron, iron salts, microorganisms, bacteria, lactobacilli, fungi, yeast, prebiotics, probiotics, unsaturated fatty acids, omega-3 fatty acids, mid-chain triglycerides, nutritional supplements, enzymes, amylases, proteases, lipases, pectinases, cellulases, hemicellulases, pentosanases, xylanases, and phytases, pigments, oligopeptides, dipeptides, amino acids and mixtures thereof.  
     
     
         20 . The system of  claim 1  wherein said nano-particles have an average particle diameter between about 0.01 microns and about 10 microns.  
     
     
         21 . The system of  claim 15  wherein said moisture sensitive microparticle releases an effective amount of said second active agent to provide a burst of said active agent.  
     
     
         22 . The system of  claim 20  wherein after said burst of said second active agent, said second active agent is continuously released for an extended period of time.  
     
     
         23 . canceled.  
     
     
         24 . An oral care product comprising the system of  claim 1 .  
     
     
         25 . A toothpaste suitable for use in oral care comprising the system of  claim 1 .  
     
     
         26 . A chewing gum suitable for use in oral care comprising the system of  claim 1 .  
     
     
         27 . A confectionary composition suitable for use in oral care comprising the system of  claim 1 .  
     
     
         28 . A pharmaceutical composition suitable for use in oral care comprising the system of  claim 1 .  
     
     
         29 . A dentifrice composition suitable for use in oral care comprising the system of  claim 1 .  
     
     
         30 . canceled.  
     
     
         31 . canceled.  
     
     
         32 . canceled.  
     
     
         33 . canceled.  
     
     
         34 . canceled.  
     
     
         35 . canceled.  
     
     
         36 . canceled.  
     
     
         37 . canceled.  
     
     
         38 . canceled.  
     
     
         39 . canceled.  
     
     
         40 . canceled.  
     
     
         41 . canceled.  
     
     
         42 . canceled.  
     
     
         43 . canceled.  
     
     
         44 . canceled.  
     
     
         45 . A beverage product comprising the system of  claim 1 .  
     
     
         46 . The beverage product of  claim 45  wherein said beverage product comprises a powdered drink mix or a liquid beverage.  
     
     
         47 . The beverage product of  claim 45  wherein said first active agent comprises a flavorant, sensory marker or nutraceutical.  
     
     
         48 . The beverage product of  claim 45  wherein said flavorant is selected from the group consisting of: crystalline ingredients, dairy ingredients, spices, natural flavors, artificial flavors, thickening agents, protein compounds, vegetable gums and combinations thereof.  
     
     
         49 . The beverage product of  claim 45  wherein said second active agent is a first flavor and said first active agent is a second flavor, said first flavor being different than said second flavor wherein release of said first flavor and said second flavor provides an organoleptic perception of a flavor transition.  
     
     
         50 . The beverage product of  claim 45  wherein said nutraceutical comprises a nutraceutical component selected from the group consisting of: antioxidants, phytochemicals, hormones, vitamins, Vitamin A, Vitamin B1, Vitamin B2, Vitamin B6, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K, pantothenate, folic acid, pro-vitamins, minerals, calcium, selenium, magnesium salts, iron, iron salts, microorganisms, bacteria, lactobacilli, fungi, yeast, prebiotics, probiotics, unsaturated fatty acids, omega-3 fatty acids, mid-chain triglycerides, nutritional supplements, enzymes, amylases, proteases, lipases, pectinases, cellulases, hemicellulases, pentosanases, xylanases, and phytases, pigments, oligopeptides, dipeptides, amino acids and mixtures thereof.  
     
     
         51 . A beverage product comprising the system of  claim 45  wherein said first active agent comprises a flavorant, sensory marker or nutraceutical.  
     
     
         52 . The beverage product of  claim 51  wherein said flavorant is selected from the group consisting of: crystalline ingredients, dairy ingredients, spices, natural flavors, artificial flavors, thickening agents, protein compounds, vegetable gums and combinations thereof.  
     
     
         53 . The beverage product of  claim 51  wherein said nutraceutical comprises a nutraceutical component selected from the group consisting of: antioxidants, phytochemicals, hormones, vitamins, Vitamin A, Vitamin B1, Vitamin B2, Vitamin B6, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K, pantothenate, folic acid, pro-vitamins, minerals, calcium, selenium, magnesium salts, iron, iron salts, microorganisms, bacteria, lactobacilli, fungi, yeast, prebiotics, probiotics, unsaturated fatty acids, omega-3 fatty acids, mid-chain triglycerides, nutritional supplements, enzymes, amylases, proteases, lipases, pectinases, cellulases, hemicellulases, pentosanases, xylanases, and phytases, pigments, oligopeptides, dipeptides, amino acids and mixtures thereof.  
     
     
         54 . A controlled release delivery system for delivery to biological surfaces comprising an oral cavity or mucous membranes of various tissues, said system comprising: 
 a plurality of solid nano-particles, each of said solid nano-particles comprising a core formed of a hydrophobic material said hydrophobic material is selected from the group consisting of natural waxes, regenerated waxes, synthetic waxes, vegetable waxes, animal waxes, mineral waxes, cholesterol, fatty acid esters, fatty alcohols, solid hydrogenated plant oils, hard paraffin, hard fats, cellulose derivatives, biodegradable polymers, copolymers of lactic acid and glycolic acid, synthetic polymers, triglycerides and mixtures thereof and an effective amount of a first active agent contained therein and a bioadhesive positively charged surfactant entrapped on a surface of each of said solid nano-particles surrounding said core said positively charged surfactant is selected from the group consisting of straight-chain alkylammonium compounds, cyclic alkylammonium compounds, petroleum derived cationics, polymeric cationic materials, polymeric amines, water insoluble polymers, cationic derivatives of polysaccharides and mixtures thereof, wherein the first active agent is an antibacterial agent selected from the group consisting of thimerosal, chloramine, boric acid, phenol, iodoform, chlorhexidine, oral antiseptic, beta-lactam antibiotic, cefoxitin, n-formamidoyl thienamycin, thienamycin derivatives, tetracycline, chloramphenicol, neomycin, gramicidin, kanamycin, amikacin, sismicin and tobramycin.    
     
     
         55 . A toothpaste suitable for use in oral care comprising: 
 a controlled release delivery system for delivery to biological surfaces comprising an oral cavity or mucous membranes of various tissues, said system comprising:    a plurality of solid nano-particles, each of said solid nano-particles comprising a core formed of a hydrophobic material said hydrophobic material is selected from the group consisting of natural waxes, regenerated waxes, synthetic waxes, vegetable waxes, animal waxes, mineral waxes, cholesterol, fatty acid esters, fatty alcohols, solid hydrogenated plant oils, hard paraffin, hard fats, cellulose derivatives, biodegradable polymers, copolymers of lactic acid and glycolic acid, synthetic polymers, triglycerides and mixtures thereof and an effective amount of a first active agent contained therein and a bioadhesive positively charged surfactant entrapped on a surface of each of said solid nano-particles surrounding said core said positively charged surfactant is selected from the group consisting of straight-chain alkylammonium compounds, cyclic alkylammonium compounds, petroleum derived cationics, polymeric cationic materials, polymeric amines, water insoluble polymers, cationic derivatives of polysaccharides and mixtures thereof.    
     
     
         56 . An oral rinse suitable for use in oral care comprising: 
 a controlled release delivery system for delivery to biological surfaces comprising an oral cavity or mucous membranes of various tissues, said system comprising:    a plurality of solid nano-particles, each of said solid nano-particles comprising a core formed of a hydrophobic material said hydrophobic material is selected from the group consisting of natural waxes, regenerated waxes, synthetic waxes, vegetable waxes, animal waxes, mineral waxes, cholesterol, fatty acid esters, fatty alcohols, solid hydrogenated plant oils, hard paraffin, hard fats, cellulose derivatives, biodegradable polymers, copolymers of lactic acid and glycolic acid, synthetic polymers, triglycerides and mixtures thereof and an effective amount of a first active agent contained therein and a bioadhesive positively charged surfactant entrapped on a surface of each of said solid nano-particles surrounding said core said positively charged surfactant is selected from the group consisting of straight-chain alkylammonium compounds, cyclic alkylammonium compounds, petroleum derived cationics, polymeric cationic materials, polymeric amines, water insoluble polymers, cationic derivatives of polysaccharides and mixtures thereof.    
     
     
         57 . A gel suitable for use in oral care comprising: 
 a controlled release delivery system for delivery to biological surfaces comprising an oral cavity or mucous membranes of various tissues, said system comprising:    a plurality of solid nano-particles, each of said solid nano-particles comprising a core formed of a hydrophobic material said hydrophobic material is selected from the group consisting of natural waxes, regenerated waxes, synthetic waxes, vegetable waxes, animal waxes, mineral waxes, cholesterol, fatty acid esters, fatty alcohols, solid hydrogenated plant oils, hard paraffin, hard fats, cellulose derivatives, biodegradable polymers, copolymers of lactic acid and glycolic acid, synthetic polymers, triglycerides and mixtures thereof and an effective amount of a first active agent contained therein and a bioadhesive positively charged surfactant entrapped on a surface of each of said solid nano-particles surrounding said core said positively charged surfactant is selected from the group consisting of straight-chain alkylammonium compounds, cyclic alkylammonium compounds, petroleum derived cationics, polymeric cationic materials, polymeric amines, water insoluble polymers, cationic derivatives of polysaccharides and mixtures thereof.    
     
     
         58 . A breath spray suitable for use in oral care comprising: 
 a controlled release delivery system for delivery to biological surfaces comprising an oral cavity or mucous membranes of various tissues, said system comprising:    a plurality of solid nano-particles, each of said solid nano-particles comprising a core formed of a hydrophobic material said hydrophobic material is selected from the group consisting of natural waxes, regenerated waxes, synthetic waxes, vegetable waxes, animal waxes, mineral waxes, cholesterol, fatty acid esters, fatty alcohols, solid hydrogenated plant oils, hard paraffin, hard fats, cellulose derivatives, biodegradable polymers, copolymers of lactic acid and glycolic acid, synthetic polymers, triglycerides and mixtures thereof and an effective amount of a first active agent contained therein and a bioadhesive positively charged surfactant entrapped on a surface of each of said solid nano-particles surrounding said core said positively charged surfactant is selected from the group consisting of straight-chain alkylammonium compounds, cyclic alkylammonium compounds, petroleum derived cationics, polymeric cationic materials, polymeric amines, water insoluble polymers, cationic derivatives of polysaccharides and mixtures thereof.    
     
     
         59 . A method for treating periodontal disease comprising inserting into a periodontal pocket; 
 a controlled release delivery system for delivery to biological surfaces comprising an oral cavity or mucous membranes of various tissues, said system comprising:    a plurality of solid nano-particles, each of said solid nano-particles comprising a core formed of a hydrophobic material said hydrophobic material is selected from the group consisting of natural waxes, regenerated waxes, synthetic waxes, vegetable waxes, animal waxes, mineral waxes, cholesterol, fatty acid esters, fatty alcohols, solid hydrogenated plant oils, hard paraffin, hard fats, cellulose derivatives, biodegradable polymers, copolymers of lactic acid and glycolic acid, synthetic polymers, triglycerides and mixtures thereof and an effective amount of a first active agent contained therein and a bioadhesive positively charged surfactant entrapped on a surface of each of said solid nano-particles surrounding said core said positively charged surfactant is selected from the group consisting of straight-chain alkylammonium compounds, cyclic alkylammonium compounds, petroleum derived cationics, polymeric cationic materials, polymeric amines, water insoluble polymers, cationic derivatives of polysaccharides and mixtures thereof.