US 12,440,463 B2
Modified release orally administered amino acid formulations
Alberto Reiner, Como (IT); and Giorgio Reiner, Como (IT)
Assigned to APR APPLIED PHARMA RESEARCH S.A., Balerna (CH)
Filed by APR APPLIED PHARMA RESEARCH S.A., Balerna (CH)
Filed on Apr. 27, 2022, as Appl. No. 17/660,999.
Application 17/660,999 is a continuation of application No. 15/303,121, granted, now 11,419,837, previously published as PCT/IB2016/055773, filed on Sep. 27, 2016.
Claims priority of provisional application 62/233,695, filed on Sep. 28, 2015.
Prior Publication US 2022/0347142 A1, Nov. 3, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/198 (2006.01); A21D 2/24 (2006.01); A21D 13/80 (2017.01); A23L 33/15 (2016.01); A23L 33/16 (2016.01); A23L 33/175 (2016.01); A61K 9/00 (2006.01); A61K 9/16 (2006.01); A61K 9/20 (2006.01); A61K 9/50 (2006.01); A61K 9/51 (2006.01); A61K 31/00 (2006.01); A61K 31/401 (2006.01); A61K 31/405 (2006.01); A61K 31/4172 (2006.01); A61K 33/00 (2006.01); A61P 3/00 (2006.01); A61P 3/02 (2006.01)
CPC A61K 31/198 (2013.01) [A21D 2/245 (2013.01); A21D 13/80 (2017.01); A23L 33/15 (2016.08); A23L 33/16 (2016.08); A23L 33/175 (2016.08); A61K 9/0053 (2013.01); A61K 9/0056 (2013.01); A61K 9/1635 (2013.01); A61K 9/1652 (2013.01); A61K 9/205 (2013.01); A61K 9/5015 (2013.01); A61K 9/5047 (2013.01); A61K 9/5073 (2013.01); A61K 9/5115 (2013.01); A61K 9/5123 (2013.01); A61K 9/5138 (2013.01); A61K 9/5161 (2013.01); A61K 31/00 (2013.01); A61K 31/401 (2013.01); A61K 31/405 (2013.01); A61K 31/4172 (2013.01); A61K 33/00 (2013.01); A61P 3/00 (2018.01); A23V 2002/00 (2013.01); A61K 2300/00 (2013.01)] 16 Claims
OG exemplary drawing
 
1. A method of treating phenylketonuria comprising orally administering to a subject in need thereof, an effective amount of a modified release amino acid formulation, the formulation comprising a plurality of modified release granules and a plurality of tyrosine-containing granules, the modified release granules comprising:
a) a sodium alginate binder admixed with an amino acid component, the amino acid component comprising at least 15 amino acids selected from the group consisting of L-alanine at 2.0 to 12.0 weight percent, L-arginine at 3.0 to 10.5 weight percent, L-aspartic acid at 5.0 to 10.5 weight percent, L-cystine at 1.5 to 4.0 weight percent, L-glutamine at 7.0 to 25.0 weight percent, glycine at 3.5 to 15.0 weight percent, L-histidine at 2.0 to 6.5 weight percent, L-isoleucine at 2.0 to 8.5 weight percent, L-leucine at 8.0 to 15.0 weight percent, L-lysine at 4.5 to 10.5 weight percent, L-methionine at 1.0 to 3.0 weight percent, L-proline at 3.5 to 15.0 weight percent, L-serine at 2.0 to 8.5 weight percent, L-threonine at 4.0 to 7.5 weight percent, L-tryptophan at 1.0 to 4.0 weight percent, L-valine at 2.5 to 10.0 weight percent, L-carnitine, L-glutamic acid, and taurine; and
b) an ethylcellulose coating layer that coats the modified release granules; and
wherein
no more than 70% of the amino acids in the formulation are released after 30 minutes when the formulation is subjected to dissolution testing in a <711>USP 39 NF 34 paddle apparatus at 37° C. in 500 ml 0.1 N hydrochloric acid at a paddle speed of 50 rpm,
further wherein
the L-Tyrosine is present in the formulation from 2.5-14.0 weight %.