Enzyme delivery systems and methods of preparation and use
This invention relates to coated digestive enzyme preparations and enzyme delivery systems and pharmaceutical compositions comprising the preparations. This invention further relates to methods of preparation and use of the systems, pharmaceutical compositions and preparations to treat persons having ADD, ADHD, autism, cystic fibrosis and other behavioral and neurological disorders.
1. A method of treating a subject having an Attention Deficit Disorder (ADD), comprising administering to the subject a pharmaceutical composition that comprises a coated digestive enzyme preparation, wherein the coated digestive enzyme preparation comprises coated particles that comprise:
(a) a core that comprises digestive enzymes, wherein the digestive enzymes comprise a protease, an amylase and a lipase; and
(b) a coating that comprises an emulsifiable lipid, wherein the coating coats the core,
wherein the digestive enzymes are present in the coated particles in an amount of from about 75% to about 85% by weight, and
wherein the coating masks the taste and smell of the digestive enzymes.
2. The method of claim 1 , wherein the emulsifiable lipid is a hydrogenated soy oil.
3. The method of claim 1 , wherein the coating consists essentially of one or more monoglycerides.
4. The method of claim 1 , wherein the coating comprises monoglycerides.
5. The method of claim 1 , wherein the emulsifiable lipid is selected from the group consisting of monoglycerides, diglycerides, fatty acids, esters of fatty acids, phospholipids, salts thereof, and a combination thereof.
6. The method of claim 5 , comprising the esters of fatty acids, wherein the esters of fatty acids are selected from the group consisting of acetic acid esters of mono- and diglycerides, citric acid esters of mono- and diglycerides, lactic acid esters of mono- and diglycerides, polyglycerol esters of fatty acids, propylene glycol esters of fatty acids, and diacetyl tartaric acid esters of mono- and diglycerides.
7. The method of claim 1 , wherein the emulsifiable lipid is a food grade emulsifiable lipid.
8. The method of claim 7 , wherein the food grade emulsifiable lipid comprises a sorbitan monostearate, a sorbitan tristearate, or a calcium stearoyl lactylate.
9. The method of claim 1 , wherein the emulsifiable lipid is a hydrogenated castor wax or a carnauba wax.
10. The method of claim 1 , wherein the digestive enzymes have a protease activity of not less than 156 United States Pharmacopeia (U.S.P.) units/mg.
11. The method of claim 1 , wherein the digestive enzymes are provided as pancreatin.
12. The method of claim 1 , wherein the core is from about 105 μm to about 425 μm.
13. The method of claim 1 , wherein the core is sieved from about 40 mesh to about 140 mesh.
14. The method of claim 1 , wherein the coated particles are non-aerosolizable.
15. The method of claim 1 , wherein about 80% of the digestive enzymes are released by 30 minutes in a dissolution test performed at pH 6.0.
16. The method of claim 1 , wherein at least 90% of the coated particles are sieved from about #40 to about #140 mesh in size.
17. The method of claim 1 , wherein less than 20% of the coated particles are capable of being sieved through #100 mesh.
18. The method of claim 1 , wherein less than 15%, of the coated particles are capable of being sieved through #100 mesh.
19. The method of claim 1 , wherein the emulsifiable lipid comprises at least one hydrophilic group and at least one hydrophobic group.
20. The method of claim 19 , wherein the emulsifiable lipid is an animal emulsifiable lipid or a vegetable emulsifiable lipid.
21. The method of claim 20 , wherein the animal emulsifiable lipid or the vegetable emulsifiable lipid is selected from the group consisting of a palm kernel oil, a soybean oil, a cottonseed oil, a canola oil and a poultry fat.
22. The method of claim 19 , wherein the emulsifiable lipid is capable of forming a hydrophilic and hydrophobic interface.
23. The method of claim 22 , wherein the hydrophilic and hydrophobic interface is a micelle interface.
24. The method of claim 22 , wherein the hydrophilic and hydrophobic interface is a bilayer interface.
25. The method of claim 1 , wherein the emulsifiable lipid is hydrogenated, saturated or partially saturated.
26. The method of claim 1 , wherein the core is processed by a technique selected from the group consisting of encapsulation, compression, extrusion and molding.
27. The method of claim 1 , wherein at least 75% of the coated particles are sieved from about #40 to about #80 mesh in size.
28. The method of claim 1 , wherein the emulsifiable lipid comprises a hydrogenated soy oil.
29. The method of claim 1 , wherein the coating consists essentially of the emulsifiable lipid that is a hydrogenated soy oil.
30. The method of claim 1 , wherein the digestive enzymes are present in the coated particles in an amount of 75% by weight.
31. The method of claim 1 , wherein the digestive enzymes are present in the coated particles in an amount of 77.5% by weight.
32. The method of claim 1 , wherein the digestive enzymes are present in the coated particles in an amount of 80% by weight.
33. The method of claim 1 , wherein the digestive enzymes are present in the coated particles in an amount of 82.5% by weight.
34. The method of claim 1 , wherein the digestive enzymes are present in the coated particles in an amount of 85% by weight.
35. The method of claim 1 , wherein at least 90% of the coated particles are from about 105 to about 425 μm.
36. The method of claim 1 , wherein less than 20% of the coated particles are capable of being sieved through about 150 μm mesh.
37. The method of claim 1 , wherein less than 15% of the coated particles are capable of being sieved through about 150 μm mesh.
38. The method of claim 1 , wherein at least 75% of the coated particles are from about 180 to about 425 μm.
39. The method of claim 1 , wherein a therapeutically effective amount of the pharmaceutical composition is a dose that contains about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050mg, about 1100 mg, or about 1150 mg of the coated digestive enzyme preparation.
40. A method of treating a subject having an Attention Deficit Hyperactive Disorder (ADHD), comprising administering to the subject a pharmaceutical composition that comprises a coated digestive enzyme preparation, wherein the coated digestive enzyme preparation comprises coated particles that comprise:
(a) a core that comprises digestive enzymes, wherein the digestive enzymes comprise a protease, an amylase and a lipase; and
(b) a coating that comprises an emulsifiable lipid, wherein the coating coats the core,
wherein the digestive enzymes are present in the coated particles in an amount of from about 75% to about 85% by weight, and
wherein the coating masks the taste and smell of the digestive enzymes.
41. The method of claim 40 , wherein the emulsifiable lipid is a hydrogenated soy oil.
42. The method of claim 40 , wherein the coating consists essentially of one or more monoglycerides.
43. The method of claim 40 , wherein the coating comprises monoglycerides.
44. The method of claim 40 , wherein the emulsifiable lipid is selected from the group consisting of monoglycerides, diglycerides, fatty acids, esters of fatty acids, phospholipids, salts thereof, and a combination thereof.
45. The method of claim 44 , comprising the esters of fatty acids, wherein the esters of fatty acids are selected from the group consisting of acetic acid esters of mono- and diglycerides, citric acid esters of mono- and diglycerides, lactic acid esters of mono- and diglycerides, polyglycerol esters of fatty acids, propylene glycol esters of fatty acids, and diacetyl tartaric acid esters of mono- and diglycerides.
46. The method of claim 40 , wherein the emulsifiable lipid is a food grade emulsifiable lipid.
47. The method of claim 46 , wherein the food grade emulsifiable lipid comprises a sorbitan monostearate, a sorbitan tristearate, or a calcium stearoyl lactylate.
48. The method of claim 40 , wherein the emulsifiable lipid is a hydrogenated castor wax or a carnauba wax.
49. The method of claim 40 , wherein the digestive enzymes have a protease activity of not less than 156 U.S.P. units/mg.
50. The method of claim 40 , wherein the digestive enzymes are provided as pancreatin.
51. The method of claim 40 , wherein the core is from about 105 μm to about 425 μm.
52. The method of claim 40 , wherein the core is sieved from about 40 mesh to about 140 mesh.
53. The method of claim 40 , wherein the coated particles are non-aerosolizable.
54. The method of claim 40 , wherein about 80% of the digestive enzymes are released by 30 minutes in a dissolution test performed at pH 6.0.
55. The method of claim 40 , wherein at least 90% of the coated particles are sieved from about #40 to about #140 mesh in size.
56. The method of claim 40 , wherein less than 20% of the coated particles are capable of being sieved through #100 mesh.
57. The method of claim 40 , wherein less than 15%, of the coated particles are capable of being sieved through #100 mesh.
58. The method of claim 40 , wherein the emulsifiable lipid comprises at least one hydrophilic group and at least one hydrophobic group.
59. The method of claim 58 , wherein the emulsifiable lipid is an animal emulsifiable lipid or a vegetable emulsifiable lipid.
60. The method of claim 59 , wherein the animal emulsifiable lipid or the vegetable emulsifiable lipid is selected from the group consisting of a palm kernel oil, a soybean oil, a cottonseed oil, a canola oil and a poultry fat.
61. The method of claim 58 , wherein the emulsifiable lipid is capable of forming a hydrophilic and hydrophobic interface.
62. The method of claim 61 , wherein the hydrophilic and hydrophobic interface is a micelle interface.
63. The method of claim 61 , wherein the hydrophilic and hydrophobic interface is a bilayer interface.
64. The method of claim 40 , wherein the emulsifiable lipid is hydrogenated, saturated or partially saturated.
65. The method of claim 40 , wherein the core is processed by a technique selected from the group consisting of encapsulation, compression, extrusion and molding.
66. The method of claim 40 , wherein at least 75% of the coated particles are sieved from about #40 to about #80 mesh in size.
67. The method of claim 40 , wherein the emulsifiable lipid comprises a hydrogenated soy oil.
68. The method of claim 40 , wherein the coating consists essentially of the emulsifiable lipid that is a hydrogenated soy oil.
69. The method of claim 40 , wherein the digestive enzymes are present in the coated particles in an amount of 75% by weight.
70. The method of claim 40 , wherein the digestive enzymes are present in the coated particles in an amount of 77.5% by weight.
71. The method of claim 40 , wherein the digestive enzymes are present in the coated particles in an amount of 80% by weight.
72. The method of claim 40 , wherein the digestive enzymes are present in the coated particles in an amount of 82.5% by weight.
73. The method of claim 40 , wherein the digestive enzymes are present in the coated particles in an amount of 85% by weight.
74. The method of claim 40 , wherein at least 90% of the coated particles are from about 105 to about 425 μm.
75. The method of claim 40 , wherein less than 20% of the coated particles are capable of being sieved through about 150 μm mesh.
76. The method of claim 40 , wherein less than 15% of the coated particles are capable of being sieved through about 150 μm mesh.
77. The method of claim 40 , wherein at least 75% of the coated particles are from about 180 to about 425 μm.
78. The method of claim 40 , wherein a therapeutically effective amount of the pharmaceutical composition is a dose that contains about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1050mg, about 1100 mg, or about 1150 mg of the coated digestive enzyme preparation.