Pharmaceutical compositions and methods for the treatment of metabolic and liver disorders
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- VIKING THERAPEUTICS INC
- Filing Date
- 2026-06-03
- Publication Date
- 2026-07-10
Smart Images
Figure 00000000_0000_ABST
Abstract
Description
This article discloses oral compositions of small molecule GLP-1 agonists and GIP / GLP-1 dual receptor agonists, and their applications. Abstract
Claims
WHAT IS CLAIMED IS:
1. A pharmaceutical composition, comprising: a permeability enhancer; and a therapeutically effective amount of a compound, wherein the compound is a GLP-1 agonist or a GLP / GIP dual agonist; wherein the mass of the permeability enhancer is greater than 300 mg.
2. The pharmaceutical composition of claim 1, wherein the compound is a compound having the structure of Formula (I), or a pharmaceutically acceptable salt thereof: (I)and a 5-10 membered heteroaryl containing 1-2 heteroatoms selected from N, O and S optionally substituted with 1-2 R7independently selected from halogen, C1-6alkyl, haloC1-6alkyl, haloC1-6 alkoxy, –OR5, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; R2is selected from the group consisting of –C(=O)(OZ2), –P(=O)(X)(Y) and a 5-10 membered heteroaryl containing 1-2 heteroatoms selected from N, O and S optionally substituted with 1-2 R7independently selected from halogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6alkoxy, –OR5, C3-10cycloalkyl, C6-10aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; each R7may be independently selected from the group consisting of halogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkoxy, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl;X and Y may each be independently selected from the group consisting of –OR4, NR5R6, C1-6 alkyl and haloC1-6 alkyl; each R4may be independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6alkyl, C6-10aryloxy and C6-10aryl alkoxy; each R5may be independently hydrogen or C1-6 alkyl; each R6may be independently hydrogen or C1-6 alkyl; and Z1and Z2may each be independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkoxy, C3-10 cycloalkyl and C6-10 aryl.
3. The pharmaceutical composition of claim 2, wherein at least one of Z1and Z2is not hydrogen.
4. The pharmaceutical composition of claim 2 or 3, wherein the compound is a compound having the structure of Formula (I-a): or a pha5. The pharmaceutical composition of claim 4, wherein Z1is selected from the group consisting of hydrogen, C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, C1-6alkoxy, C3-10cycloalkyl and C6-10aryl; and X and Y each are –OR4.
6. The pharmaceutical composition of claim 4 or 5, wherein Z1is selected from the group consisting of hydrogen, haloC1-6alkoxy and C1-6alkoxy; and each R4independently is selected from the group consisting of hydrogen, C6-10aryloxy and C6-10aryl alkoxy.
7. The pharmaceutical composition of any one of claims 4 to 6, wherein Z1is hydrogen and each R4independently is hydrogen or C6-10 aryl alkoxy.
8. The pharmaceutical composition of any one of claims 4 to 7, wherein each R4is hydrogen.
9. The pharmaceutical composition of any one of claims 4 to 8, wherein Z1is hydrogen and each R4is hydrogen.
10. The pharmaceutical composition of claim 2, wherein the compound is a compound having the structure of Formula (I-b): or a pha11. The pharmaceutical composition of claim 10, wherein Z2is selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkoxy, C3-10 cycloalkyl and C6-10aryl; and X and Y each are –OR4.
12. The pharmaceutical composition of claim 10 or 11, wherein Z2is selected from the group consisting of hydrogen, haloC1-6 alkoxy and C1-6 alkoxy; and each R4independently is selected from the group consisting of hydrogen, C6-10 aryloxy and C6-10 aryl alkoxy.
13. The pharmaceutical composition of claim 10 or 11, wherein Z2is hydrogen and each R4is hydrogen or C6-10 aryl alkoxy.
14. The pharmaceutical composition of any one of claims 10 to 13, wherein each R4is hydrogen.
15. The pharmaceutical composition of any of claims 10 to 14, wherein Z2is hydrogen and each R4is hydrogen.
16. The pharmaceutical composition of claim 2, wherein the compound is a compound having the structure of Formula (I-c): or a ph17. The pharmaceutical composition of claim 16, wherein X and Y each are –OR4.
18. The pharmaceutical composition of claim 16 or 17, wherein each R4is independently selected from the group consisting of hydrogen, C6-10 aryloxy and C6-10 aryl alkoxy.
19. The pharmaceutical composition of any one of claims 16 to 18, wherein each R4is hydrogen.
20. The pharmaceutical composition of claim 2 or 3, wherein the compound is a compound having the structure selected from the group consisting of:-120-and pharmaceutically acceptable salts thereof.
21. The pharmaceutical composition of claim 20, wherein the compound is a compound having the structure:or a pharmaceutically acceptable salt thereof.
22. The pharmaceutical composition of any one of claims 2 to 21 , whereinindicates a chiral carbon with “S” configuration.
23. The pharmaceutical composition of any one of claims 2 to 21, wherein indicates a chiral carbon with “R” configuration.
24. The pharmaceutical composition of claim 1, wherein the compound is a compound having the structure of Formula (II),or a pharmaceutically acceptable salt thereof, wherein:Aib is 2-aminoisobutyric acid;each instance of J1, J2, and J3is independently an amino acid selected from Aib, a naturally occurring amino acid, and an unnatural amino acid; U1is -(J4)n1-(J5)n2-(J6)n3-(J7)n4-; U2is -(J8)n5-(J9)n6-(J10)n7-(J11)n8-; each instance of J4, J5, J6, J7, J8, J9, J10, and J11is independently a naturally occurring amino acid or an unnatural amino acid; each of n1, n2, n3, n4, n5, n6, n7, and n8 is independently 0 or 1, provided that the sum n1 + n2 + n3 + n4 + n5 + n6 + n7 + n8 is 4; R1is selected from the group consisting of –C(=O)(OZ1), –P(=O)(X)(Y) and a 5-10 membered heteroaryl containing 1-2 heteroatoms selected from N, O and S, the heteroaryl optionally substituted with 1-2 R7independently selected from halogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, –OR5, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; R2is selected from the group consisting of –C(=O)(OZ2), –P(=O)(X)(Y) and a 5-10 membered heteroaryl containing 1-2 heteroatoms selected from N, O and S, the heteroaryl optionally substituted with 1-2 R7independently selected from halogen, C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, –OR5, C3-10cycloalkyl, C6-10aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; each R7is independently selected from the group consisting of halogen, C1-6 alkyl, haloC1-6alkyl, haloC1-6alkoxy, C1-6alkoxy, C3-10cycloalkyl, C6-10aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; X and Y each are independently selected from the group consisting of –OR4, NR5R6, C1-6 alkyl and haloC1-6 alkyl; each R4is independently selected from the group consisting of hydrogen, C1-6alkyl, haloC1-6 alkyl, C6-10 aryl and C7-11 arylalkyl; each R5is independently hydrogen or C1-6 alkyl; each R6is independently hydrogen or C1-6alkyl; and Z1and Z2each are independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkoxy, C3-10 cycloalkyl and C6-10aryl.
25. The pharmaceutical composition of claim 24, wherein the compound is not:(SEQ ID NO: 7).
26. The pharmaceutical composition of claim 24 or 25, wherein each instance of J1, J2, and J3is independently an amino acid selected from Aib and a naturally occurring amino acid.
27. The pharmaceutical composition of any one of claims 24 to 26, wherein each instance of J1, J2, and J3is independently an amino acid selected from Aib, A, F, N, R, and Q.
28. The pharmaceutical composition of any one of claims 24 to 27, wherein J1is Aib or F.
29. The pharmaceutical composition of any one of claims 24 to 28, wherein J1is F.
30. The pharmaceutical composition of any one of claims 24 to 29, wherein J2is N or Q.
31. The pharmaceutical composition of any one of claims 24 to 30, wherein J2is N.
32. The pharmaceutical composition of any one of claims 24 to 31, wherein J3is A or R.
33. The pharmaceutical composition of any one of claims 24 to 32, wherein J3is R.
34. The pharmaceutical composition of any one of claims 24 to 33, wherein each instance of J4, J5, J6, and J7is independently an amino acid selected from A, I, K, R, Q, S, T, and V.
35. The pharmaceutical composition of any one of claims 24 to 34, wherein J4is K or R.
36. The pharmaceutical composition of any one of claims 24 to 35, wherein J4is R.
37. The pharmaceutical composition of any one of claims 24 to 36, wherein J5is I, T, or V.
38. The pharmaceutical composition of any one of claims 24 to 37, wherein J5is T or V.
39. The pharmaceutical composition of any one of claims 24 to 38, wherein J6is A or s.
40. The pharmaceutical composition of any one of claims 24 to 39, wherein J6is S.
41. The pharmaceutical composition of any one of claims 24 to 40, wherein J7is Q or K.
42. The pharmaceutical composition of any one of claims 24 to 41, wherein each instance of J8, J9, J10, and J11is independently an amino acid selected from A, I, and Q.
43. The pharmaceutical composition of any one of claims 24 to 42, wherein J8is I orQ.
44. The pharmaceutical composition of any one of claims 24 to 43, wherein J9is A or Q.
45. The pharmaceutical composition of any one of claims 24 to 44, wherein J10is Q.
46. The pharmaceutical composition of any one of claims 24 to 45, wherein J11is Q.
47. The pharmaceutical composition of any one of claims 24 to 27, whereinJ1is selected from Aib or F;J2is selected from Q or N;J3is selected from A or R;U1is selected from -K-V-A-, -K-I-A-Q- (SEQ ID NO: 8), -K-T-A-Q- (SEQ ID NO: 9), -K-T-S-Q- (SEQ ID NO: 10), -K-V-A-Q- (SEQ ID NO: 11), -R-I-A-Q- (SEQ ID NO: 12), K-I-A-K- (SEQ ID NO: 13), -K-I-S-Q- (SEQ ID NO: 14), or is absent; andU2is selected from -Q-, -I-A-Q-Q- (SEQ ID NO: 15), -I-A-Q-K- (SEQ ID NO:16), -V-A-Q-K (SEQ ID NO: 17), or is absent.
48. The pharmaceutical composition of any one of claims 24 to 47, wherein each instance of nl, n2, n3, and n4 is zero.
49. The pharmaceutical composition of any one of claims 24 to 47, wherein each instance of n4, n6, n7, and n8 is zero.
50. The pharmaceutical composition of any one of claims 24 to 47, wherein each instance of n5, n6, n7, and n8 is zero.
51. The pharmaceutical composition of any one of claims 24 to 50, wherein at least one of Z1and Z2is not hydrogen.
52. The pharmaceutical composition of any one of claims 24 to 51 , wherein the compound is a compound having the structure of Formula (Il-a):or a pharmaceutically acceptable salt thereof.
53. The pharmaceutical composition of claim 52, wherein Z1is selected from the group consisting of hydrogen, Ci-6 alkyl, haloCi-6 alkyl, haloCi-6 alkoxy, Ci-6 alkoxy, C3-10 cycloalkyl and Ce-io aryl; and X and Y each are -OR4.
54. The pharmaceutical composition of claim 51, wherein Z1is hydrogen and each R4independently is hydrogen or C7-11 arylalkyl.
55. The pharmaceutical composition of claim 53 or 54, wherein each R4is hydrogen.
56. The pharmaceutical composition of claim 51, wherein Z1is hydrogen and each R4is hydrogen.
57. The pharmaceutical composition of any one of claims 23 to 51, wherein the compound is a compound having the structure of Formula (Il-b):or a pharmaceutically acceptable salt thereof.
58. The pharmaceutical composition of claim 57, wherein each R4is independently selected from the group consisting of hydrogen, Ce-io aryl and C7-11 arylalkyl.
59. The pharmaceutical composition of claim 58, wherein each R4is hydrogen.
60. The pharmaceutical composition of claim 24 or 25, wherein the compound is a compound having the structure selected from the group consisting of:(SEQ ID NO: 22) (SEQ ID NO: 26) and pharmaceutically acceptable salts thereof.
61. The pharmaceutical composition of claim 1, wherein the compound is a compound having the structure of Formula (III), or a pharmaceutically acceptable salt thereofor a pharmaceutically acceptable salt thereof, wherein: R1is selected from the group consisting of –C(=O)(OZ1), –P(=O)(X)(Y) and a 5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O and S optionally substituted with 1-2 R7independently selected from halogen, C1-6 alkyl, haloC1-6 alkyl, haloC1- 6 alkoxy, –OR5, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; R2is selected from the group consisting of –C(=O)(OZ2), –(CH2CH2)nP(=O)(X)(Y) and a 5-10 membered heteroaryl containing 1-4 heteroatoms selected from N, O and S optionally substituted with 1-2 R7independently selected from halogen, C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, –OR5, C3-10cycloalkyl, C6-10aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; each R7is independently selected from the group consisting of halogen, C1-6 alkyl, haloC1-6alkyl, haloC1-6alkoxy, C1-6alkoxy, C3-10cycloalkyl, C6-10aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; X and Y each are independently selected from the group consisting of –OR4, NR5R6, C1-6alkyl and haloC1-6alkyl; each R4is independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6 alkyl, C6-10 aryloxy and C6-10 aryl alkoxy; each R5is independently hydrogen or C1-6alkyl; each R6is independently hydrogen or C1-6 alkyl; Z1and Z2each are independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6alkyl, haloC1-6alkoxy, C1-6alkoxy, C3-10cycloalkyl and C6-10aryl; andn is 0, 1, 2, 3 or 4.
62. The pharmaceutical composition of claim 61, wherein at least one of Z1and Z2is not hydrogen.
63. The pharmaceutical composition of claim 61 or 62, wherein the compound is a compound having the structure of Formula (III-a):
64. The pharmaceutical composition of claim 63, wherein Z is selected from the group consisting of hydrogen, C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, C1-6alkoxy, C3-10cycloalkyl and C6-10 aryl; and X and Y each are –OR4.
65. The pharmaceutical composition of claims 63 or 64, wherein Z1is selected from the group consisting of hydrogen, haloC1-6alkoxy and C1-6alkoxy; and each R4independently is selected from the group consisting of hydrogen, C6-10aryloxy and C6-10aryl alkoxy.
66. The pharmaceutical composition of any one of claims 63 to 65, wherein Z1is hydrogen and each R4independently is hydrogen or C6-10aryl alkoxy.
67. The pharmaceutical composition of any one of claims 63 to 66, wherein each R4is hydrogen.
68. The pharmaceutical composition of any one of claims 63 to 67, wherein Z1is hydrogen and each R4is hydrogen.
69. The pharmaceutical composition of any one of claims 63 to 68, wherein n is 1.
70. The pharmaceutical composition of any one of claims 63 to 68, wherein n is 2.
71. The pharmaceutical composition of claim 59, wherein the compound is a having the structure of Formula (III-b):O O H X P N2* OZ OH o72. The pharmaceutical composition of claim 71, wherein Z2is selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkoxy, C3-10 cycloalkyl and C6-10 aryl; and X and Y each are –OR4.
73. The pharmaceutical composition of claim 71 or 72, wherein Z2is selected from the group consisting of hydrogen, haloC1-6 alkoxy and C1-6 alkoxy; and each R4independently is selected from the group consisting of hydrogen, C6-10 aryloxy and C6-10 aryl alkoxy.
74. The pharmaceutical composition of any one of claims 71 to 73, wherein Z2is hydrogen and each R4is hydrogen or C6-10 aryl alkoxy.
75. The pharmaceutical composition of any one of claims 71 to 74, wherein each R4is hydrogen.
76. The pharmaceutical composition of any one of claims 71 to 75, wherein Z2is hydrogen and each R4is hydrogen.
77. The pharmaceutical composition of any one of claims 71 to 76, wherein n is 1.
78. The pharmaceutical composition of any one of claims 71 to 76, wherein n is 2.
79. The pharmaceutical composition of claim 61 or 62, wherein the compound is a compound having the structure of Formula (III-c):or a pharmaceutically acceptable salt thereof.
80. The pharmaceutical composition of claim 79, wherein X and Y each are –OR4.
81. The pharmaceutical composition of claim 80, wherein each R4independently is selected from the group consisting of hydrogen, C6-10aryloxy and C6-10aryl alkoxy.
82. The pharmaceutical composition of claim 80 or 81, wherein each R4is hydrogen.
83. The pharmaceutical composition of any one of claims 79 to 82, wherein n is 1.
84. The pharmaceutical composition of any one of claims 79 to 82, wherein n is 2.
85. The pharmaceutical composition of claim 61 or 62, wherein the compound is a compound having the structure selected from the group consisting of: ,and pharmaceutically acceptable salts thereof.
86. The pharmaceutical composition of any one of claims 61 to 85, whereinindicates a chiral carbon with “S” configuration.
87. The pharmaceutical composition of any one of claims 61 to 85, wherein indicates a chiral carbon with “R” configuration.
88. The pharmaceutical composition of any one of Claims 1 to 87, wherein the mass of the permeability enhancer is from about 350 mg to about 1000 mg.
89. The pharmaceutical composition of any one of Claims 1 to 87, wherein the mass of the permeability enhancer is from about 400 mg to about 800 mg.
90. The pharmaceutical composition of any one of Claims 1 to 87, wherein the mass of the permeability enhancer is from about 500 mg to about 750 mg.
91. The pharmaceutical composition of any one of Claims 1 to 87, wherein the mass of the permeability enhancer is about 500 mg; or wherein the mass of the permeability enhancer is 450 mg.
92. The pharmaceutical composition of any one of Claims 1 to 91, wherein the permeability enhancer comprises from about 40% to about 90% by weight of the composition.
93. The pharmaceutical composition of any one of Claims 1 to 91, wherein the permeability enhancer comprises from about 50% to about 80% by weight of the composition.
94. The pharmaceutical composition of any one of Claims 1 to 91, wherein the one or more permeability enhancer comprises from about 70% to about 80% by weight of the composition.
95. The pharmaceutical composition of any one of Claims 1 to 91, wherein the permeability enhancer comprises about 73% of the composition.
96. The pharmaceutical composition of any one of Claims 1 to 95, wherein the permeability enhancer is salcaprozate sodium (SNAC), sodium caprate (CIO), or a combination thereof.
97. The pharmaceutical composition of any one of Claims 1 to 95, wherein the permeability enhancer is salcaprozate sodium.
98. The pharmaceutical composition of any one of Claims 1 to 95, wherein the permeability enhancer is sodium caprate.
99. The pharmaceutical composition of any one of Claims 1 to 95, wherein the one or more permeability enhancer is a combination of salcaprozate sodium and sodium caprate.
100. The pharmaceutical composition of any one of Claims 1 to 99, comprising from about 1 mg to about 50 mg of the compound.
101. The pharmaceutical composition of any one of Claims 1 to 99, comprising from about 5 mg to about 40 mg of the compound.
102. The pharmaceutical composition of any one of Claims 1 to 99, comprising from about 10 mg to about 30 mg of the compound.
103. The pharmaceutical composition of any one of Claims 1 to 99, comprising from about 20 mg to about 30 mg of the compound.
104. The pharmaceutical composition of any one of Claims 1 to 99, comprising from about 25 mg of the compound.
105. The pharmaceutical composition of any one of Claims 1 to 104, further comprising a disintegrant.
106. The pharmaceutical composition of Claim 105, wherein the disintegrant is croscarmellose sodium.
107. A pharmaceutical composition, comprising: salcaprozate sodium; and a therapeutically effective amount of a compound having the structure of Formula I, or a pharmaceutically acceptable salt thereof:, Y) and a 5-10 membered heteroaryl containing 1-2 heteroatoms selected from N, O and S optionally substituted with 1-2 R7independently selected from halogen, C1-6 alkyl, haloC1-6 alkyl, haloC1- 6 alkoxy, –OR5, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; R2is selected from the group consisting of –C(=O)(OZ2), –P(=O)(X)(Y) and a 5-10 membered heteroaryl containing 1-2 heteroatoms selected from N, O and S optionallysubstituted with 1-2 R7independently selected from halogen, C1-6alkyl, haloC1-6alkyl, haloC1-6 alkoxy, –OR5, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; each R7is independently selected from the group consisting of halogen, C1-6alkyl, haloC1-6 alkyl, haloC1-6 alkoxy, C1-6 alkoxy, C3-10 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl and 5-10 membered heterocyclyl; X and Y each are independently selected from the group consisting of –OR4, NR5R6, C1-6 alkyl and haloC1-6 alkyl; each R4is independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6alkyl, C6-10aryl and C6-10arylalkyl; each R5is independently hydrogen or C1-6alkyl each R6is independently hydrogen or C1-6 alkyl; and Z1and Z2each are independently selected from the group consisting of hydrogen, C1-6 alkyl, haloC1-6alkyl, haloC1-6alkoxy, C1-6alkoxy, C3-10cycloalkyl and C6-10aryl; and wherein the mass of salcaprozate is greater than about 300 mg.
108. The pharmaceutical composition of any one of Claims 1 to 107, wherein at least one of Z1and Z2is not hydrogen.
109. The pharmaceutical composition of any one of Claims 1 to 107, wherein the composition further comprises one or more excipient.
110. The pharmaceutical composition of Claim 109, wherein the one or more excipient is selected from the group consisting of microcrystalline cellulose, magnesium stearate, and polyvinylpyrrolidone.
111. The pharmaceutical composition of any one of Claims 1 to 110, wherein the compound has the structure of Formula I-a:
112. The pharmaceutical composition of any one of Claims 1 to 111, wherein Z1is selected from the group consisting of hydrogen, C1-6alkyl, haloC1-6alkyl, haloC1-6alkoxy, C1-6 alkoxy, C3-10 cycloalkyl and C6-10 aryl; and X and Y each are –OR4.
113. The pharmaceutical composition of any one of Claims 1 to 112, wherein Z1is selected from the group consisting of hydrogen, haloC1-6alkoxy and C1-6alkoxy; and each R4independently is selected from the group consisting of hydrogen, C6-10aryl and C6-10arylalkyl.
114. The pharmaceutical composition of any one of Claims 1 to 113, wherein Z1is hydrogen and each R4independently is hydrogen or C6-10arylalkyl.
115. The pharmaceutical composition of any one of Claims 1 to 114, wherein each R4is hydrogen.
116. The pharmaceutical composition of any one of Claims 1 to 115, wherein the compound is:or a pharmaceutically acceptable salt thereof.
117. The pharmaceutical composition of any one of Claims 1 to 116, wherein the composition is formulated for oral administration.
118. The pharmaceutical composition of any one of Claims 1 to 117, wherein the pharmaceutical composition comprises: from about 1.0 to about 5.0% by weight of the compound; from about 50% to about 80% by weight salcaprozate sodium; from about 10% to about 30% by weight microcrystalline cellulose; from about 1.0% to about 3.0% by weight polyvinylpyrrolidinone; and from about 1.0% to about 3.0% by weight magnesium stearate.
119. The pharmaceutical composition of any one of Claims 1 to 118, wherein the pharmaceutical composition comprises: about 3.6% by weight of the compound; about 72.7% by weight salcaprozate sodium; about 19.4% by weight microcrystalline cellulose; about 1.9% by weight polyvinylpyrrolidinone; and about 2.3% by weight magnesium stearate.
120. The pharmaceutical composition of any one of Claims 1 to 119, wherein the pharmaceutical composition is enterically coated.
121. A method of preventing, treating, or ameliorating one or more metabolic disorders or metabolic syndromes in a subject, comprising administering a pharmaceutical composition of any one of Claims 1 to 120, to a subject in need thereof.
122. The method of Claim 119, wherein the metabolic disorder or metabolic syndrome is atherosclerosis, diabetes, hyperglycemic diabetes, type 2 diabetes mcllitus, dyslipidemia, hypercholesterolemia, hyperlipidemia, hypertension, hypoglycemia, obesity, hypothalamic obesity, or prader-willi syndrome.
123. The method of Claim 119 or 120, wherein the metabolic disorder or metabolic syndrome is obesity or hypothalamic obesity.
124. A method of preventing, treating, or ameliorating one or more fatty liver diseases in a subject, comprising administering a pharmaceutical composition of any one of Claims 1 to 120, to a subject in need thereof.
125. The method of Claim 122, wherein said wherein said fatty liver disease is selected from the group consisting of steatosis, non-alcoholic steatohepatitis and non-alcoholic fatty liver disease.
126. The method of Claim 122 or 125, wherein said administration of said pharmaceutical composition results in the prevention, treatment, or amelioration, of a fibrosis, fibrotic condition, or fibrotic symptoms.
127. The method of any one of Claims 122 to 126, wherein said administration of said pharmaceutical composition results in the reduction in the amount of extracellular matrix proteins present in one or more tissues of said subject.
128. The method of any of Claims 122 to 127, wherein said administration of said pharmaceutical composition results in the reduction in the amount of collagen present in one or more tissues of said subject.
129. The method of Claim 128, wherein said administration of said pharmaceutical composition results in the reduction in the amount of Type I, Type la, or Type III collagen present in one or more tissues of said subject.
130. A method of preventing, treating, or ameliorating one or disease or disorders in a subject, comprising administering a pharmaceutical composition of any one of Claims 1 to 118 to a subject in need thereof, wherein said disease or disorder is liver fibrosis, renal fibrosis, biliary fibrosis, pancreatic fibrosis, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, chronic kidney disease, diabetic kidney disease, primary sclerosing cholangitis, primary bi 1 iary cirrhosis, or idiopathic fibrosis.
131. The method of Claim 130, wherein said disease or disorder is nonalcoholic stcatohcpatitis, non-alcoholic fatty liver disease, chronic kidney disease, diabetic kidney disease, primary sclerosing cholangitis, or primary biliary cirrhosis.
132. The method of any one of Claims 121 to 131, wherein the route of administration is oral.
133. A method of preparing a pharmaceutical composition, the method comprising the steps of:(i) combining salcaprozate sodium and magnesium stearate to form first granules;(ii) combining microcrystalline cellulose, Compound 4, and polyvinylpyrrolidinone to form second granules(iii) combining the first granules and the second granules to form a mixture;(iv) adding magnesium stearate to the mixture to form third granules;(v) pressing the third granules into tablets.
134. A method of preparing a pharmaceutical composition, the method comprising the steps of:(i) combining microcrystalline cellulose and compound disclosed therein in a first vessel;(ii) combining polyvinylpyrrolidinone and water in a second vessel;(iii) adding the contents of the first vessel to the second vessel to form wet granules;(iv) drying the wet granules to form dry granules;(v) combining the dry granules with magnesium stearate; and(vi) pressing the resulting mixture of step (v) into granules.
135. The pharmaceutical composition prepared by the method of Claim 133 or 134.