Compositions for Oral Administration of Sustained Release Glutathione, Methods for Their Production and Uses Thereof
A composition suitable for oral administration for sustained-release of glutathione, the composition having from about 50% by weight to about 90% by weight glutathione; from about 0% by weight to about 10% by weight binder; from about 10% by weight to about 50% by weight of at least one sustained release agent; and a granule size of from about 850 μm to about 5000 μm, is provided. Methods for preparing such compositions are also provided. Uses and methods of medical treatment by orally administering a composition for sustained release of glutathione to a patient suffering from or at risk of suffering from a neurological disorder are also provided.
1 . A composition suitable for oral administration for sustained-release of glutathione, the composition comprising:
a) from about 50% by weight to about 90% by weight glutathione;
b) from about 0% by weight to about 10% by weight binder;
c) from about 10% by weight to about 50% by weight of at least one sustained release agent; and
d) a granule size of from about 500 μm to about 5000 μm.
2 . The composition of claim 1 wherein said composition provides sustained release of glutathione over a period of from about 2 hours to about 12 hours.
3 . The composition of claim 1 wherein said composition provides sustained release of glutathione over a period of from about 4 hours to about 8 hours.
4 . The composition of claim 1 wherein the granule size is from about 500 μm to about 2000 μm.
5 . (canceled)
6 . (canceled)
7 . (canceled)
8 . (canceled)
9 . The composition of claim 1 further comprising a glidant.
10 . The composition of claim 9 wherein the glidant is silicon dioxide.
11 . The composition of claim 1 further comprising leucine.
12 . The composition of claim 1 wherein the glutathione is present at from about 60% by weight to about 80% by weight.
13 . (canceled)
14 . (canceled)
15 . The composition of claim 1 wherein the binder is present at from about 0% by weight to about 5% by weight.
16 . (canceled)
17 . The composition of claim 16 wherein the binder is Kollidon™ 30.
18 . (canceled)
19 . The composition of claim 1 wherein the at least one sustained release agent is present at from about 20% by weight to about 40% by weight.
20 . (canceled)
21 . (canceled)
22 . The composition of claim 1 wherein the at least one sustained release agent is selected from at least one of the group consisting of: Methocel™ KMlOOP CR, and Methocel™ E4M CR.
23 . (canceled)
24 . (canceled)
25 . The composition of claim 1 where the at least one sustained release agent comprises Methocel™ KMl 00P CR and Methocel™ E4M CR.
26 . The composition of claim 25 wherein the Methocel™ KMl 00P CR is present at about 21.7% by weight and the Methocel™ E4M CR is present at about 5.5% by weight.
27 . The composition of claim 1 suitable for administration to a patient having a gastric pH of from about 1 to about 7.
28 .- 41 . (canceled)
42 . A composition comprising about 70% by weight glutathione, about 2.8% by weight Kollidon™ 30, about 21.7% by weight Methocel™ KMlOOP CR, about 5.5% by weight Methocel™ E4M CR and having a granule size not more than about 850 μm.
43 . A composition comprising about 72% by weight Glutathione, about 22.3% by weight Methocel™ KMlOOP CR, about 5.7% by weight Methocel™ E4M CR and having a granule size not more than about 850 μm.
44 . The composition of claim 42 or 43 wherein the granule size is about 850 μm.
45 . A composition containing about 70% by weight glutathione, about 2.8% by weight Kollidon™ 30, about 21.7% by weight Methocel™ KMlOOP CR, about 5.5% by weight Methocel™ E4M CR having a granule size not more than about 850 μm
46 . A composition containing about 72% by weight Glutathione, about 22.3% by weight Methocel™ KMlOOP CR, about 5.7% by weight Methocel™ E4M CR and having a granule size not more than about 850 μm.
47 . The composition of claim 45 or 46 further containing a trace amount of leucine and a trace amount of silicon dioxide.
48 . A method for preparing a sustained-release composition comprising glutathione, suitable for oral administration, the method comprising:
mixing glutathione and a binder, thereby forming a mixture;
adding a granulating agent to the mixture, thereby forming a wet mixture;
granulating the wet mixture, thereby forming a granulation, such that the granulation comprises granules larger than about 850 μm;
removing granules less than about 500 μm from the granulation;
blending at least one sustained release agent with the granulation, thereby forming a blend;
screening the blend with an 850 μm mesh, thereby forming a screened blend; and
reblending the screened blend.
49 . The method of claim 48 wherein the mixing occurs for a duration of from about 2 minutes to about 6 minutes.
50 . (canceled)
51 . The method of claim 48 wherein the adding occurs for a duration of from about 4 minutes to about 9 minutes.
52 . The method of claim 48 wherein the adding occurs for a duration of about 6.5 minutes.
53 . A method for preparing a sustained-release composition comprising glutathione, suitable for oral administration, the method comprising:
blending two sustained release agents together, thereby forming a blend;
screening the blend with a 20 US standard mesh screen, thereby forming a screened-blend;
granulating the screened-blend thereby forming a granulation;
reblending the granulation with glutathione thereby forming a re-blend;
rescreening the re-blend with a 20 US standard mesh screen thereby forming a re-screened-blend;
regranulating the re-screened-blend thereby forming a re-granulation; and
rescreening the re-granulation with a 20 US standard mesh screen.
54 . The method of claims 48 or 53 further comprising mixing a glidant with said composition.
55 . The method of claims 48 or 53 further comprising mixing leucine with said composition.
56 . The method of claims 48 or 53 further comprising encapsulating said composition.
57 . The method of claims 48 or 53 wherein the blending occurs for a duration of from about 2 minutes to about 6 minutes.
58 . (canceled)
59 . The method of claims 48 or 53 wherein the reblending occurs for a duration of from about 2 minutes to about 10 minutes.
60 .- 61 . (canceled)
62 . A method of medical treatment comprising orally administering a composition for sustained release of glutathione to a patient suffering from or at risk of suffering from a neurological disorder.
63 . The method of medical treatment of claim 62 wherein the neurological disorder is selected from the group consisting of: Multiple Sclerosis, Autism, Alzheimer's disease, Parkinson's disease, Aphasia, Bell's Palsy, Creutzfeldt-Jakob disease, Epilepsy, Encephalitis, Huntington's disease, neuromuscular disorders, neuro-oncology, neuro-immunology, dementia and neuro-otology.
64 .- 67 . (canceled)
68 . A method of medical treatment comprising administering the composition of claim 1 to a patient in need thereof, thereby maintaining a serum glutathione concentration in a patient for a duration of from about 2 hours to about 12 hours for the treatment of a neurological disorder.
69 . A method of medical treatment comprising administering the composition of claim 1 to a patient suffering from or at risk of suffering from a neurological disorder.
70 . A method of medical treatment comprising administering the composition of claim 1 to a patient suffering from or at risk of suffering from at least one of the neurological disorders selected from the group consisting of: Multiple Sclerosis, Autism, Alzheimer's disease, Parkinson's disease, Aphasia, Bell's Palsy, Creutzfeldt-Jakob disease, Epilepsy, Encephalitis, Huntington's disease, neuromuscular disorders, neuro-oncology, neuro-immunology, dementia and neuro-otology.
71 .- 75 . (canceled)
76 . The method of any one of claims 68 to 70 wherein the patient is further suffering from low gastric acidity.
77 .- 118 . (canceled)