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

• US 20030152629A1
• Filed: 03/13/2003
• Published: 08/14/2003
• Est. Priority Date: 10/25/2000
• Status: Active Grant

• Current Assignee: Adi Shefer, Samuel David Shefer
• Original Assignee: Adi Shefer, Samuel David Shefer
• Inventors: Shefer, Adi, Shefer, Samuel David
• Granted Patent: US 6,887,493 B2
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A23G 1/54 Composite products, e.g. layered laminated, coated, filled
• CPC Class Codes: A23L 2/39 Dry compositions
• CPC Class Codes: A23L 27/72 Encapsulation
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/25 Nanoparticles, nanostructures
• CPC Class Codes: A61K 2800/412 Microsized, i.e. having sizes between 0.1 and 100 microns
• CPC Class Codes: A61K 2800/413 Nanosized, i.e. having sizes below 100 nm
• CPC Class Codes: A61K 2800/56 Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
• CPC Class Codes: A61K 8/0241 Containing particulates characterized by their shape and/or structure see also A61K8/04, A61K8/11, and A61K8/14, further aspects are classified in A61K2800/40 and subcodes
• CPC Class Codes: A61K 8/11 Encapsulated compositions
• CPC Class Codes: A61K 8/347 Phenols
• CPC Class Codes: A61K 8/4926 having six membered rings
• CPC Class Codes: A61K 8/92 Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
• CPC Class Codes: A61K 8/922 of vegetable origin
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/0063 Periodont
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1641 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61P 1/02 : Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 3/02 : Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61Q 11/00 : Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

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.

Claims

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. The system of claim 1 wherein said hydrophobic material has a melting point between 30°

C. and 90°

C.

3. The system of claim 2 wherein said hydrophobic material comprises carnauba wax.

4. The system of claim 2 wherein said hydrophobic material comprises candelilla wax.

5. The system of claim 1 wherein said moisture sensitive matrix material releases said active agent upon contact with moisture and continuously thereafter for an extended period of time.

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. The system of claim 1 wherein said natural gum is gum arabic.

8. The system of claim 1 wherein said nano-particle further comprises a surfactant.

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-ld-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 14 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. A method for producing the system of claim 1 comprising the steps of:

(i) heating said hydrophobic material to a temperature above the melting point of said hydrophobic material to form a melt;

(ii) dissolving or dispersing said first active agent into said melt;

(iii) dissolving or dispersing said moisture sensitive matrix material and said bioadhesive material in the aqueous phase to form a composition;

(iv) heating the composition to a temperature above the melting point of the mixture formed in step (ii) to form a hot melt;

(v) mixing said hot melt of step (ii) with the aqueous solution formed in step (iii) to form a dispersion;

(vi) high shear homogenization of said suspension at a temperature above the melting temperature of said material mixture formed in step (v) until a homogeneous fine dispersion is obtained;

(vii) rapidly cooling said suspension to ambient temperature to form a dispersion; and

(viii) spray drying said cooled dispersion to form a dry powder composition.

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. A food product comprising the system of claim 1.

31. The food product of claim 29 wherein said first active agent comprises a flavorant, sensory marker or nutraceutical.

32. The food product of claim 30 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.

33. The food product of claim 30 wherein said nutraceutical is 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.

34. A food product of claim 15 wherein said first active agent and said second active agent are selected from one or more of a flavorant, sensory marker, or nutraceutical.

35. The food product of claim 33 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.

36. The food product 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.

37. The food product of claim 33 wherein said nutraceutical is 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.

38. A hydratable sauce or soupcomposition comprising the system of claim 1.

39. The hydratable sauce or soup composition of claim 36 wherein said first active agent comprises a flavorant, sensory marker or nutraceutical.

40. The hydratable sauce or soup composition of claim 37 wherein said flavorant is selected from the group consisting of:

crystalline ingredients, dairy ingredients, natural flavors, artificial flavors, thickening agents, protein compounds, vegetable gums and combinations thereof.

41. The hydratable sauce or soup composition of claim 37 wherein said nutraceutical is 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.

42. The hydratable sauce or soup of claim 15 wherein said first active agent and said second active agent are selected from one or more of a flavorant, sensory marker, or nutraceutical.

43. The hydratable sauce or soup of claim 40 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.

44. The hydratable sauce or soup of claim 40 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.

45. A beverage product comprising the system of claim 1.

46. The beverage product of claim 32 wherein said beverage product comprises a powdered drink mix or a liquid beverage.

47. The beverage product of claim 43 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 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.

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 15 wherein said first active agent comprises a flavorant, sensory marker or nutraceutical.

52. The beverage product of claim 48 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 48 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.