Lipase-containing composition and methods of use thereof
Disclosed are compositions including crosslinked lipase crystals that are highly resistant to proteolysis, low pH and elevated temperature.
1 . A composition comprising
a non-fungal lipase crystal crosslinked with a multifunctional crosslinking agent;
a protease; and
an amylase,
wherein the lipase crystal is active at a pH range from about 2.0 to 9.0.
2 . The composition of claim 1 , wherein the lipase crystal is active at a pH range from about 1.0 to 6.0.
3 . The composition of claim 1 , wherein the lipase crystal is active at a pH range from about 1.5 to 3.0.
4 . The composition of claim 1 , wherein the lipase crystal is active following exposure for at least one hour to an environment having pH 1.0 to 4.0.
5 . The composition of claim 1 , wherein the lipase crystal is active following exposure for at least two hours to an environment having pH 1.0 to 4.0.
6 . The composition of claim 1 , wherein the lipase crystal is active following exposure for at least five hours to an environment having pH 1.0 to 4.0.
7 . The composition of claim 1 , wherein the multifunctional crosslinking agent is Bis (Sulfosuccinimidyl) suberate.
8 . The composition of claim 1 , wherein the lipase crystal is derived from a bacterial lipase.
9 . The composition of claim 8 , wherein the bacterial lipase is a Pseudomonas lipase.
10 . The composition of claim 1 , wherein the composition is provided in a powder form.
11 . The composition of claim 1 , wherein the composition is provided as an aqueous slurry.
12 . The composition of claim 1 , wherein said protease is provided as a crystal.
13 . The composition of claim 12 , wherein said protease crystal is provided as a cross-linked enzyme crystal.
14 . The composition of claim 1 , wherein said amylase is provided as a crystal.
15 . The composition of claim 14 , wherein said amylase is provided as a cross-linked enzyme crystal.
16 . The composition of claim 12 , wherein said amylase is provided as a cross-linked enzyme crystal.
17 . The composition of claim 1 , wherein said protease is provided in an amorphous form.
18 . The composition of claim 1 , wherein said amylase is provided in an amorphous form.
19 . The composition of claim 17 , wherein said amylase is provided in an amorphous form.
20 . The composition of claim 1 , wherein the amylase is selected from the group consisting of a Bacillus amylase and an Aspergillus amylase.
21 . The composition of claim 1 , wherein said protease is selected from the group consisting of plant and fungal proteases.
22 . The composition of claim 1 , wherein said protease is selected from the group consisting of bromelain, papain, and ficin.
23 . The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
24 . The composition of claim 23 , wherein the composition is present in a formulation suitable for oral delivery to a subject.
25 . The composition of claim 23 , wherein the carrier is selected from the group consisting of a diluent, excipient, and adjuvant.
26 . The composition of claim 23 , wherein the carrier is a polymeric carrier.
27 . The composition of claim 24 , wherein the polymeric carrier is a biodegradable polymer.
28 . The composition of claim 24 , wherein the composition is encapsulated within a matrix of the polymeric carrier.
29 . The composition of claim 28 , wherein at least 50% of the composition remains encapsulated within the matrix following exposure of the polymeric carrier to an environment having pH 1.0 to 3.0 for at least one hour.
30 . The composition of claim 24 , wherein the composition is administered preprandially, prandially, or postprandially.
31 . A composition comprising
a Burkholderia cepacia lipase crystal,
bromelain; and
an Aspergillus amylase,
wherein the lipase crystal is active at a pH range from about 2.0 to 9.0.
32 . The composition of claim 31 , wherein said lipase crystal is crosslinked.
33 . A method for treating or preventing a gastrointestinal disorder in a mammal, the method comprising administering to a mammal in need thereof a therapeutically effective amount of the composition of claim 1 .
34 . The method of claim 33 , wherein the composition is administered orally.
35 . The method of claim 33 , wherein the mammal is a human.
36 . The method of claim 33 , wherein the gastrointestinal disorder is selected from the group consisting of pancreatitis and pancreatic insufficiency.
37 . The method of claim 33 , wherein the subject suffers from or is at risk for cystic fibrosis.
38 . A method for treating or preventing fat malabsorption in a mammal suffering from or at risk for a condition characterized by low lipase secretion, the method comprising to the mammal the composition of claim 1 .
39 . The method of claim 38 , wherein the composition is administered orally to the mammal.
40 . The method of claim 38 , wherein the mammal is a human.
41 . The method of claim 38 , wherein the composition is administered preprandially to the subject.
42 . The method of claim 38 , wherein the composition is administered prandially to the subject.
43 . The method of claim 38 , wherein the composition is administered postprandially to the subject.
44 . The method of claim 38 , wherein the composition is administered to the mammal in an amount sufficient to increase the coefficient of fat absorption in the mammal to greater than 60%.
45 . The method of claim 38 , wherein the composition is administered to the mammal in an amount sufficient to increase the coefficient of fat absorption in the mammal to greater than 80%.
46 . The method of claim 38 , wherein the composition is administered to the mammal in an amount sufficient to increase the coefficient of protein absorption in the mammal to greater than 60%.
47 . A method for treating or preventing fat malabsorption in a mammal suffering from or at risk for a condition characterized by low lipase secretion, the method comprising to the mammal the composition of claim 31.