Microcapsules and emulsions containing low bloom gelatin and methods of making and using thereof

• US 6,969,530 B1
• Filed: 01/21/2005
• Issued: 11/29/2005
• Est. Priority Date: 01/21/2005
• Status: Active Grant

• Current Assignee: DSM Nutritional Products AG (DSM-Firmenich AG)
• Original Assignee: Ocean Nutrition Canada Limited (DSM-Firmenich AG)
• Inventors: Zhang, Wei, Jin, Yulai, Curtis, Jonathan Michael
• Primary Examiner(s): Acquah, Samuel A.
• Application Number:
  US11/040,820
• Time in Patent Office: 312 Days
• Field of Search: 264/4.1, 264/4.3, 264/4.32, 264/4.33, 264/4.4, 264/4.7, 428/402.21, 428/402.24, 428/403, 428/489, 428/494, 428/496, 428/497, 428/498
• US Class Current: 424/489
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/5057 Gelatin
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: B01J 13/10 Complex coacervation, i.e. interaction of oppositely charged particles
• CPC Class Codes: Y10T 428/2985 Solid-walled microcapsule from synthetic polymer
• CPC Class Codes: Y10T 428/2989 Microcapsule with solid core [includes liposome]
• CPC Class Codes: Y10T 428/2991 Coated

Abstract

Described herein are microcapsules and emulsions prepared from low Bloom gelatin and methods of making and using thereof.

Claims

1. A microcapsule comprising an agglomeration of primary microcapsules and a loading substance, each individual primary microcapsule having a primary shell, wherein the loading substance is encapsulated by the primary shell, wherein the agglomeration is encapsulated by an outer shell, wherein the primary shell and/or the outer shell comprises gelatin having a Bloom number less than 50.

2. The microcapsule of claim 1, wherein the primary shell and/or the outer shell further comprises a protein, a polyphosphate, a polysaccharide, or a mixture thereof.

3. The microcapsule of claim 1, wherein the primary shell and/or the outer shell further comprises high Bloom gelatin type A, gelatin type B, polyphosphate, gum arabic, alginate, chitosan, carrageenan, pectin, starch, modified starch, alfa-lactalbumin, beta-lactoglobumin, ovalbumin, polysorbiton, maltodextrins, cyclodextrins, cellulose, methyl cellulose, ethyl cellulose, hydropropylmethylcellulose, carboxymethylcellulose, milk protein, whey protein, soy protein, canola protein, albumin, kosher gelatin, non-kosher gelatin, Halal gelatin, non-Halal gelatin, or a mixture thereof.

4. The microcapsule of claim 1, wherein the primary shell and the outer shell comprises a complex coacervate.

5. The microcapsule of claim 1, wherein the gelatin has a Bloom number of less than 40.

6. The microcapsule of claim 1, wherein the gelatin has a Bloom number of less than 30.

7. The microcapsule of claim 1, wherein the gelatin has a Bloom number of less than 20.

8. The microcapsule of claim 1, wherein the gelatin has a Bloom number of less than 10.

9. The microcapsule of claim 1, wherein the gelatin has a Bloom number of zero.

10. The microcapsule of claim 1, wherein the gelatin is gelatin type A having a Bloom number of zero.

11. The microcapsule of claim 1, wherein the primary shell and the outer shell comprises gelatin having a Bloom number of less than 50.

12. The microcapsule of claim 1, wherein the primary shell and the outer shell comprises a complex coacervate between gelatin having a Bloom number of zero and polyphosphate.

13. The microcapsule of claim 1, wherein the microcapsule further comprises an antioxidant.

14. The microcapsule of claim 13, wherein the antioxidant comprises a phenolic compound, a plant extract, or a sulphur-containing amino acid.

15. The microcapsule of claim 13, wherein the antioxidant comprises ascorbic acid or a salt of ascorbic acid.

16. The microcapsule of claim 1, wherein the outer shell has an average diameter of from about 1 μ

m to about 2,000 μ

m.

17. The microcapsule of claim 1, wherein the outer shell has an average diameter of from about 20 μ

m to about 1,000 μ

m.

18. The microcapsule of claim 1, wherein the outer shell has an average diameter of from about 20 μ

m to about 100 μ

m.

19. The microcapsule of claim 1, wherein the outer shell has an average diameter of from about 30 μ

m to about 80 μ

m.

20. The microcapsule of claim 1, wherein the primary shells have an average diameter of from about 40 μ

m to about 10 μ

m.

21. The microcapsule of claim 1, wherein the primary shells have an average diameter of from about 0.1 μ

m to about 5 μ

m.

22. The microcapsule of claim 1, wherein the primary shells have an average diameter of about 1 μ

m.

23. The microcapsule of claim 1, wherein the loading substance is from 20% to 90% by weight of the microcapsule.

24. The microcapsule of claim 1, wherein the loading substance is from 50% to 70% by weight of the microcapsule.

25. The microcapsule of claim 1, wherein the loading substance comprises a grease, an oil, a lipid, a drug, a biologically active substance, a nutritional supplement, a flavour compound, or a mixture thereof.

26. The microcapsule of claim 1, wherein the loading substance comprises fish oil.

27. The microcapsule of claim 1, wherein the loading substance comprises an omega-3 fatty acid or an ester or triglyceride of an omega-3 fatty acid.

28. The microcapsule of claim 1, wherein the loading substance comprises eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, an ester or triglyceride thereof, or a mixture thereof.

29. The microcapsule of claim 1, wherein the loading substance comprises a phytosterol ester of docosahexaenoic acid and/or eicosapentaenoic acid, a C₁–

C₆ alkyl ester of docosahexaenoic acid and/or eicosapentaenoic acid, an ester or triglyceride thereof, or a mixture thereof.

30. The microcapsule of claim 1, wherein the primary shell and the outer shell comprises a complex coacervate between gelatin having a Bloom number of zero and polyphosphate, and the loading substance comprises eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, an ester or triglyceride thereof, or a mixture thereof.

31. The microcapsule of claim 1, wherein the loading substance further comprises an antioxidant, wherein the antioxidant comprises CoQ₁₀, vitamin E, a tocopherol, a lipid soluble derivative of a polar antioxidant, a plant extract, an algal extract, or a synthetic antioxidant.

32. The microcapsule of claim 1, further comprising one or more additional shells surrounding the outer shell, wherein at least one of the primary, outer, and additional shells comprise a complex coacervate.

33. The microcapsule of claim 1, further comprising one or more processing aid in the primary and/or the outer shells, wherein the processing aid comprises an emulsifier, a fatty acid, a lipid, a wax, a microbial cell, a clay, an inorganic compound, or any combination thereof.

80. A foodstuff comprising the microcapsule of claim 1.

81. The foodstuff of claim 80, wherein the foodstuff is a baked good, a pasta, a meat product, a frozen dairy product, a milk product, a cheese product, an egg product, a condiment, a soup mix, a snack food, a nut product, a plant protein product, a hard candy, a soft candy, a poultry product, a processed fruit juice, a granulated sugar, a sauce, a gravy, a syrup, a nutritional bar, a beverage, a dry beverage powder, a jam or jelly, a fish product, or pet companion food.

82. The foodstuff of claim 80, wherein the foodstuff is bread, tortillas, cereal, sausage, chicken, ice cream, yogurt, milk, salad dressing, rice bran, fruit juice, a dry beverage powder, rolls, cookies, crackers, fruit pies, or cakes.

83. A foodstuff comprising the microcapsule of claim 1.

84. The foodstuff of claim 83, wherein the foodstuff is kosher or Halal.

91. A pharmaceutical formulation comprising the microcapsule of claim 1 and a pharmaceutically acceptable carrier.

95. A method for delivering a loading substance to a subject, comprising administering to the subject the microcapsule of claim 1.

96. The method of claim 95, wherein the subject is a mammal.

97. The method of claim 95, wherein the subject is a human.

98. The method of claim 95, wherein the subject is a domesticated animal.

99. The method of claim 95, wherein the subject is a mice, a rat, a cow, a horse, a sheep, a goat, a primate, a fish, a shellfish, a crustacean, a bird, a dog, or a cat.

34. A microcapsule comprising a loading substance, a primary shell, and a secondary shell, wherein the primary shell encapsulates the loading substance, and the secondary shell encapsulates the loading substance and primary shell, wherein the primary shell and/or the secondary shell comprises gelatin having a Bloom number less than 50.

35. The microcapsule of claim 34, wherein the primary shell and the secondary shell comprises a complex coacervate.

36. The microcapsule of claim 34, wherein the primary shell and/or the secondary shell further comprises a protein, a polyphosphate, a polysaccharide, or a mixture thereof.

37. The microcapsule of claim 34, wherein the primary shell and/or the secondary shell further comprises high Bloom gelatin type A, gelatin type B, polyphosphate, gum arabic, alginate, chitosan, carrageenan, pectin, starch, modified starch, alfa-lactalbumin, beta-lactoglobumin, ovalbumin, polysorbiton, maltodextrins, cyclodextrins, cellulose, methyl cellulose, ethyl cellulose, hydropropylmethylcellulose, carboxymethylcellulose, milk protein, whey protein, soy protein, canola protein, albumin, kosher gelatin, non-kosher gelatin, Halal gelatin, non-Halal gelatin, or a mixture thereof.

38. The microcapsule of claim 34, wherein the gelatin is gelatin type A having a Bloom number of zero.

39. The microcapsule of claim 34, wherein the primary and/or secondary shell comprises a complex coacervate between zero Bloom gelatin and polyphosphate.

40. The microcapsule of claim 34, wherein the loading substance is from 20% to 90% by weight of the microcapsule.

41. The microcapsule of claim 34, wherein the loading substance is from 50% to 70% by weight of the microcapsule.

42. The microcapsule of claim 34, wherein the microcapsule has a diameter of from 1 μ

m to 2,000 μ

m.

43. The microcapsule of claim 34, wherein the microcapsule has a diameter of from 20 μ

m to 100 μ

m.

44. The microcapsule of claim 34, wherein the microcapsule has a diameter of from 30 μ

m to 80 μ

m.

85. A foodstuff comprising the microcapsule of claim 34.

86. The foodstuff of claim 85, wherein the foodstuff is kosher or Halal.

92. A pharmaceutical formulation comprising the microcapsule of claim 34 and a pharmaceutically acceptable carrier.

100. A method for delivering a loading substance to a subject, comprising administering to the subject the microcapsule of claim 34.

45. An emulsion comprising a loading substance and a gelatin having a Bloom number less than 50.

46. The emulsion of claim 45, wherein the emulsion further comprises a protein, a polyphosphate, a polysaccharide, or a mixture thereof.

47. The emulsion of claim 45, wherein the emulsion further comprises high Bloom gelatin type A, gelatin type B, polyphosphate, gum arabic, alginate, chitosan, carrageenan, pectin, starch, modified starch, alfa-lactalbumin, beta-lactoglobumin, ovalbumin, polysorbiton, maltodextrins, cyclodextrins, cellulose, methyl cellulose, ethyl cellulose, hydropropylmethylcellulose, carboxymethylcellulose, milk protein, whey protein, soy protein, canola protein, albumin, kosher gelatin, Halal gelatin, or a mixture thereof.

48. The emulsion of claim 45, wherein the emulsion further comprises an antioxidant, a surfactant, a metal ion chelator, a flavorant, or a viscosifier.

49. The emulsion of claim 45, wherein the gelatin is gelatin type A having a Bloom number of zero.

89. A foodstuff comprising the emulsion of claim 45.

90. The foodstuff of claim 89, wherein the foodstuff is kosher or Halal.

94. A pharmaceutical formulation comprising the emulsion of claim 45 and a pharmaceutically acceptable carrier.

102. A method for delivering a loading substance to a subject, comprising administering to the subject the emulsion of claim 45.

50. A process for preparing microcapsules, the process comprising:

(a) providing an aqueous mixture comprising a loading substance and a gelatin having a Bloom number less than 50;

(b) adjusting the pH, temperature, concentration, mixing speed or a combination thereof to form a primary shell comprising the gelatin around the loading substance;

(c) cooling the aqueous mixture to a temperature above the gel point of the gelatin until the primary shells form an agglomeration; and

,

(d) cooling the aqueous mixture to form an outer shell around the agglomeration.

51. The process of claim 50, wherein the aqueous mixture further comprises a second polymer component.

52. The process of claim 51, wherein the second polymer component comprises a protein, a polyphosphate, a polysaccharide, or a mixture thereof.

53. The process of claim 51, wherein the second polymer component comprises high Bloom gelatin type A, gelatin type B, polyphosphate, gum arabic, alginate, chitosan, carrageenan, pectin, starch, modified starch, alfa-lactalbumin, beta-lactoglobumin, ovalbumin, polysorbiton, maltodextrins, cyclodextrins, cellulose, methyl cellulose, ethyl cellulose, hydropropylmethylcellulose, carboxymethylcellulose, milk protein, whey protein, soy protein, canola protein, albumin, kosher gelatin, non-kosher gelatin, Halal gelatin, non-Halal gelatin, or a mixture thereof.

54. The process of claim 51, wherein the second polymer component is polyphosphate.

55. The process of claim 50, wherein the loading substance comprises a grease, an oil, a lipid, a drug, a biologically active substance, a nutritional supplement, a flavour compound, or a mixture thereof.

56. The process of claim 50, wherein the loading substance comprises fish oil.

57. The process of claim 50, wherein the loading substance comprises an omega-3 fatty acid or an ester or triglyceride of an omega-3 fatty acid.

58. The process of claim 50, wherein the loading substance comprises eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, an ester or triglyceride, or a mixture thereof.

59. The process of claim 50, wherein the loading substance is provided in an amount of from about 20% to 90% by dry weight.

60. The process of claim 50, wherein the low Bloom gelatin is provided in an amount of from about 1% to about 15% by weight of the aqueous mixture.

61. The process of claim 50, wherein an antioxidant is added to the aqueous mixture in step (a).

62. The process of claim 50, wherein step (a) comprises (i) dispersing the loading substance into the aqueous mixture of the gelatin and (ii) adding a second polymer component to the aqueous mixture of loading substance and gelatin.

63. The process of claim 50, wherein the pH in step (b) is adjusted to a value from 3.5 to 5.0.

64. The process of claim 50, wherein the pH in step (b) is adjusted to a value from 4.0 to 5.0.

65. The process of claim 50, wherein the temperature is initially from about 20°

C. to about 60°

C.

66. The process of claim 50, wherein the mixture in step (c) is cooled at a rate of 1°

C./10 minutes.

67. The process of claim 50, wherein the mixture in step (c) is cooled until it reaches a temperature of from about 3°

C. to about 10°

C.

68. The process of claim 51, further comprising adding a cross-linker to cross-link the gelatin and second polymer component.

69. The process of claim 51, further comprising after step (d) adding a cross-linker to cross-link the gelatin and second polymer component.

70. The process of claim 68, wherein the cross-linker comprises an enzymatic cross-linker, an aldehyde, tannic acid, alum, a plant extract, a phenolic compound, or a mixture thereof.

71. The process of claim 68 wherein the cross-linker is gluteraldehyde.

72. The process of claim 68, wherein the cross-linker is transglutaminase.

73. The process of claim 50, further comprising drying the microcapsule after step (d).

74. The process of claim 50, further comprising after step (d), mixing the microcapsule with a third polymer component and adjusting the pH, temperature, concentration, mixing speed or a combination thereof to form a shell material comprising the third polymer component, wherein third polymer component forms a shell around microcapsule.

78. A microcapsule produced by the process of claim 50.

87. A foodstuff comprising the microcapsule of claim 78.

88. The foodstuff of claim 87, wherein the foodstuff is kosher or Halal.

93. A pharmaceutical formulation comprising the microcapsule of claim 78 and a pharmaceutically acceptable carrier.

101. A method for delivering a loading substance to a subject, comprising administering to the subject the microcapsule of claim 78.

75. A process for preparing microcapsules, the process comprising:

(a) providing an emulsion comprising a loading substance and a gelatin having a Bloom number less than 50; and

(b) drying the emulsion to produce the microcapsules.

76. The process of claim 75, wherein the drying step comprises spray drying, freeze drying, fluidized bed drying, or drum drying.

77. The process of claim 75, wherein the drying step comprises spray drying.

79. A microcapsule produced by the process of claim 75.

103. A method for stabilizing an emulsion, comprising admixing an aqueous mixture of a loading substance with a gelatin having a Bloom number less than 50.