Calcium dicarboxylate ethers, methods of making same, and treatment of vascular disease and diabetes therewith
Alcohol and water solvates of 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt are crystalline and have the formula (I), wherein R 1 is H or lower alkyl, and x is a number from 0 to 10, and are useful for treating dyslipidemia.
1. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 1 having an x-ray powder diffraction pattern substantially comprising:
#
2-Theta
d(A)
Peak
P %
Area
Area %
FWHM
1
6.760
13.0648
5106
100.0
1497
100.0
0.234
2
8.183
10.7953
1743
34.1
435
29.1
0.200
3
8.560
10.3207
1866
36.5
543
36.3
0.233
4
9.239
9.5638
234
4.6
29
1.9
0.096
5
9.760
9.0546
972
19.0
220
14.7
0.181
6
10.569
8.3634
156
3.1
12
0.8
0.061
7
11.141
7.9353
178
3.5
29
1.9
0.130
8
13.760
6.4304
266
5.2
46
3.1
0.138
9
15.599
5.6761
338
6.6
63
4.2
0.148
10
16.740
5.2917
433
8.5
64
4.3
0.118
11
17.420
5.0866
1890
37.0
689
46.0
0.291
12
20.639
4.3000
523
10.2
128
8.5
0.196
13
21.391
4.1505
188
3.7
20
1.3
0.085
14
22.139
4.0119
445
8.7
74
4.9
0.132
15
31.559
2.8326
270
5.3
24
1.6
0.070.
2. The crystalline compound of claim 1 having a 13 C NMR (solid state) in ppm of: 189.6; 186.2; 71.4; 43.4; 30.1; 28.4; 25.2; 23.1.
3. The crystalline compound of claim 1 having a having a 13 C NMR peak at 25.2 ppm.
4. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt ethanol solvate having an x-ray powder diffraction pattern substantially comprising:
#
2-Theta
d(A)
Peak
P %
Area
Area %
FWHM
1
6.899
12.8028
13186
100.0
3025
100.0
0.184
2
8.261
10.6945
5221
39.6
931
30.8
0.143
3
8.838
9.9969
2057
15.6
482
15.9
0.187
4
11.061
7.9927
785
6.0
160
5.3
0.163
5
12.100
7.3086
1355
10.3
150
4.9
0.088
6
13.619
6.4964
450
3.4
89
2.9
0.157
7
17.677
5.0132
753
5.7
126
4.2
0.134
8
18.180
4.8755
2011
15.3
588
19.4
0.234
9
20.840
4.2588
439
3.3
40
1.3
0.072
10
21.334
4.1615
427
3.2
67
2.2
0.125.
5. The crystalline compound of claim 4 having a 13 C NMR (solid state) in ppm of: 189.9; 186.7; 71.6; 58.5; 43.2; 29.9; 23.5.
6. The crystalline compound of claim 4 having a 13 C NMR peak at 58.5 ppm.
7. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid mono-calcium salt methanol solvate having an x-ray powder diffraction pattern substantially comprising:
#
2-Theta
d(A)
Peak
P %
Area
Area %
FWHM
1
6.896
12.8072
11991
100.0
2593
100.0
0.173
2
8.339
10.5940
2046
17.1
334
12.9
0.131
3
9.219
9.5853
1438
12.0
281
10.8
0.156
4
10.280
8.5979
632
5.3
180
6.9
0.227
5
11.320
7.8105
1079
9.0
322
12.4
0.238
6
15.800
5.6044
463
3.9
59
2.3
0.102
7
16.741
5.2913
432
3.6
38
1.4
0.069
8
18.160
4.8809
1260
10.5
599
23.1
0.380
9
18.702
4.7408
700
5.8
184
7.1
0.210
10
19.816
4.4766
589
4.9
94
3.6
0.127
11
21.724
4.0876
510
4.3
96
3.7
0.150.
8. The crystalline compound of claim 7 having a 13 C NMR (solid state) in ppm of: 189.6; 186.2; 71.4; 43.2; 29.6; 23.5.
9. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-propyl alcohol solvate having an x-ray powder diffraction pattern substantially comprising:
#
2-Theta
d(A)
Peak
P %
Area
Area %
FWHM
1
6.899
12.8025
12371
100.0
3495
100.0
0.226
2
7.843
11.2637
4815
38.9
1119
32.0
0.186
3
8.661
10.2009
1709
13.8
357
10.2
0.167
4
11.359
7.7833
771
6.2
141
4.0
0.146
5
12.300
7.1900
752
6.1
127
3.6
0.135
6
13.100
6.7528
517
4.2
37
1.0
0.057
7
18.262
4.8540
1945
15.7
596
17.1
0.245
8
20.721
4.2832
828
6.7
279
8.0
0.269
9
21.740
4.0847
573
4.6
146
4.2
0.203.
10. The crystalline compound of claim 9 having a 13 C NMR (solid state) in ppm of: 189.6; 186.0; 71.6; 43.2; 29.6; 23.8.
11. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 2-propyl alcohol solvate having an x-ray powder diffraction pattern substantially comprising:
#
2-Theta
d(A)
Peak
P %
Area
Area %
FWHM
1
6.918
12.7674
10028
100.0
2562
100.0
0.204
2
8.000
11.0427
3984
39.7
800
31.2
0.161
3
8.619
10.2506
1619
16.1
346
13.5
0.171
4
11.338
7.7981
658
6.6
68
2.6
0.082
5
11.718
7.5459
236
2.4
28
1.1
0.093
6
12.241
7.2243
761
7.6
131
5.1
0.138
7
15.382
5.7557
610
6.1
107
4.2
0.140
8
18.162
4.8803
1937
19.3
441
17.2
0.182
9
20.779
4.2713
853
8.5
222
8.6
0.208.
12. The crystalline compound of claim 11 having a 13 C NMR (solid state) in ppm of: 189.4; 187.7; 70.9; 69.4; 66.5; 63.8; 432; 35.0; 30.1; 23.8; 18.7; 14.3.
13. The crystalline compound of claim 11 having a 13 C NMR peak at 63.8, 18.7, or 14.3 ppm.
14. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-butyl alcohol solvate having an x-ray powder diffraction pattern substantially comprising:
#
2-Theta
d(A)
Peak
P %
Area
Area %
FWHM
1
7.060
12.5101
19609
100.0
4796
100.0
0.196
2
9.078
9.7332
3027
15.4
567
11.8
0.150
3
11.100
7.9644
924
4.7
164
3.4
0.142
4
16.361
5.4135
554
2.8
76
1.6
0.109
5
18.040
4.9133
2276
11.6
456
9.5
0.160
6
18.820
4.7112
1303
6.6
385
8.0
0.236
7
19.922
4.4532
1886
9.6
457
9.5
0.193
8
21.560
4.1183
853
4.4
205
4.3
0.191
9
22.281
3.9867
343
1.7
37
0.8
0.086
10
23.521
3.7793
450
2.3
107
2.2
0.189.
15. The crystalline compound of claim 14 having a 13 C NMR (solid state) in ppm of: 189.9; 186.0; 71.6; 43.2; 29.9; 23.8.
16. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 2 having an x-ray powder diffraction pattern substantially comprising:
#
2-Theta
d(A)
Peak
P %
Area
Area %
FWHM
1
7.259
12.1686
9283
100.0
2482
100.0
0.214
2
8.739
10.1100
4191
45.1
603
24.3
0.115
3
9.386
8.9628
967
10.4
161
6.5
0.133
4
11.659
7.5838
430
4.6
49
1.9
0.089
5
13.955
6.3408
305
3.3
58
2.3
0.151
6
14.220
6.2233
326
3.5
73
2.9
0.178
7
15.387
5.7537
278
3.0
19
0.7
0.053
8
16.461
5.3806
986
10.6
187
7.5
0.152
9
17.361
5.1039
1490
16.1
348
14.0
0.187
10
18.063
4.9069
1284
13.8
323
13.0
0.201
11
19.302
4.5947
871
9.4
166
6.7
0.152
12
19.862
4.4664
686
7.4
142
5.7
0.166
13
20.200
4.3923
457
4.9
103
4.1
0.179
14
21.178
4.1918
656
7.1
97
3.9
0.117
15
21.641
4.1031
167
1.8
6
0.2
0.029
16
22.300
3.9833
794
8.6
192
7.7
0.193
17
23.218
3.8278
247
2.7
23
0.9
0.071
18
24.100
3.6897
183
2.0
34
1.3
0.145
19
25.481
3.4928
487
5.2
141
5.7
0.231
20
28.800
3.0974
134
1.4
14
0.6
0.083
21
29.297
3.0459
259
2.8
28
1.1
0.084
22
30.700
2.9099
287
3.1
20
0.8
0.055.
17. The crystalline compound of claim 16 having a 13 C NMR (solid sate) in ppm of: 190.9; 189.6; 186.2; 120.4; 72.7; 44.7; 44.2; 43.0; 42.3; 39.3; 37.9; 31.8; 30.9; 29.6; 27.7; 26.2; 25.3; 24.0; 22.9; 21.5; and 20.2.
18. The crystalline compound of claim 10 having a 13 C NMR peak at 72.7, 44.7, or 26.2 ppm.
19. The compound of claim 1 , wherein said crystalline structure contains from approximately 0.1 to approximately 1.0 water molecules per salt ion.
20. A method for preparing a stable crystalline compound of Formula II:
wherein R 1 is lower alkyl and x is a number from 0 to 10, comprising reacting a compound of Formula I
with calcium oxide in an alkanol organic solvent of the formula R 1 OH to yield a solid product; and drying the solid product to obtain the monocalcium dicarboxylate ether salt of the compound of Formula II having a stoichiometric ratio of calcium to dicarboxylate of approximately 1:1.
21. The method of claim 20 , wherein the organic solvent is a C 1 -C 12 alcohol.
22. The method of claim 20 , wherein the C 1 -C 12 alcohol is essentially anhydrous.
23. The method of claim 20 , wherein the alcohol is a C 1 -C 4 alkanol.
24. The method of claim 20 further comprising the step of introducing a work-up solvent into the organic alcohol solvent, wherein the work-up solvent causes at least a portion of the monocalcium dicarboxylate ether salt to precipitate from the organic alcohol solvent.
25. The method of claim 24 wherein the work-up solvent is methyl tert-butyl ether.
26. The method of claim 24 further comprising the step of filtering the solid product from the organic solvent prior to drying.
27. The method of claim 24 further comprising the step of washing the solid product with the organic work-up solvent subsequent to filtering.
28. A method for preparing a crystalline hydrate of the Formula II
wherein R 1 is H and x is a number from 0 to 10, comprising reacting an alcohol solvate of Formula II where R 1 is lower alkyl with water.
29. The method of claim 28 wherein the solid product contains between approximately 0.1 and approximately 1.0 equivalents of water per equivalent of the monocalcium dicarboxylate ether salt subsequent to said filtering step and said drying step.
30. The method of claim 20 wherein said reacting step occurs at a temperature between about 25° C. and the reflux point of the alkanol organic solvent at standard pressure.
31. The method of claim 20 wherein said reacting step occurs at a temperature between the reflux point of the alkanol organic solvent and about 150° C. at a pressure above standard pressure.
32. A method of converting the compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt hydrate Crystal Form 1 into the compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt hydrate Crystal Form 2, said method comprising the steps of: exposing the Crystal Form 1 to water, agitating the Crystal Form 1 and water; heating the Crystal Form 1 and water for sufficient time for a conversion to occur so as to yield Crystal Form 2; and drying the solid product to obtain the 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt hydrate Crystal Form 2, wherein the Crystal Form 2 has a stoichiometric ratio of calcium to dicarboxylate form of the compound of 1:1.
33. The method of claim 32 further comprising the step of filtering the Crystal Form 2 from the water prior to said drying step.
34. A pharmaceutical composition comprising 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt hydrate Crystal Form 1 together with one or more pharmaceutically acceptable diluents, carriers or excipients.
35. A pharmaceutical composition comprising 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt hydrate Crystal Form 2 together with one or more pharmaceutically acceptable diluents, carriers or excipients.
36. A method of treating diabetes in a patient in need thereof said method comprising administering to the patient a therapeutically effective amount of a compound as set forth in claim 1 .
37. A method of treating diabetes in a patient in need thereof, said method comprising administering to the patient a therapeutically effective amount of a compound as set forth in claim 16 .
38. A method of treating a vascular disease in a patient in need thereof, said method comprising administering to the patient a therapeutically effective amount of a compound as set forth in claim 1 .
39. A method of treating a vascular disease in a patient in need thereof, said method comprising administering to the patient a therapeutically effective amount of a compound as set forth in claim 16 .
40. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 1 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 6.760.
41. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 1 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 17.420.
42. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 1 that exhibits an x-ray powder diffraction pattern comprising characteristic peaks expressed in degrees 2θ at 6.760 and 17.420.
43. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 1 according to claim 42 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 8.183.
44. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 1 according to claim 42 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 8.560.
45. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 1 according to claim 42 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 9.760.
46. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 1 according to claim 42 that exhibits an x-ray powder diffraction pattern comprising at least one peak expressed in degrees 2θ at 8.183, 8.560, 9.239, 9.760, 10.569, 11.141, 13.760, 15.599, 16.740, 20.639, 21.391, 22.139, or 31.559.
47. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt ethanol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 6.899.
48. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt ethanol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 8.261.
49. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt ethanol solvate that exhibits an x-ray powder diffraction pattern comprising characteristic peaks expressed in degrees 2θ at 6.899 and 8.261.
50. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt ethanol solvate according to claim 49 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 8.838.
51. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt ethanol solvate according to claim 49 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 18.180.
52. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt ethanol solvate according to claim 49 hat exhibits an x-ray powder diffraction pattern comprising at least one peak expressed in degrees 2θ at 8.838, 11.061, 12.100, 13.619, 17.677, 18.180, 20.840, or 21.334.
53. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt methanol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peal; expressed in degrees 2θ at 6.896.
54. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid mono-calcium salt methanol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 18.160.
55. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid mono-calcium salt methanol solvate that exhibits an x-ray powder diffraction pattern comprising characteristic peaks expressed in degrees 2θ at 6.896 and 18.160.
56. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid mono-calcium salt methanol solvate according to claim 55 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 8.339.
57. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid mono-calcium salt methanol solvate according to claim 55 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 9.219.
58. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid mono-calcium salt methanol solvate according to claim 55 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 11.320.
59. The crystalline compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid mono-calcium salt methanol solvate according to claim 55 that exhibits an x-ray powder diffraction pattern comprising at least one peak expressed in degrees 2θ at 8.339, 9.219, 10.280, 11.320, 15.800, 16.741, 18.702, 19.816, or 21.724.
60. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-propyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 6.899.
61. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-propyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 7.843.
62. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-propyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising characteristic peaks expressed in degrees 2θ at 6.899 and 7.843.
63. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-propyl alcohol solvate according to claim 62 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 8.661.
64. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-propyl alcohol solvate according to claim 62 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 18.262.
65. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-propyl alcohol solvate according to claim 62 that exhibits an x-ray powder diffraction pattern comprising at least one peak expressed in degrees 2θ at 8.661, 11.359, 12.300, 13.100, 18.262, 20.721, or 21.740.
66. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 2-propyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peat expressed in degrees 2θ at 6.918.
67. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 2-propyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic pa expressed in degrees 2θ at 8.000.
68. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 2-propyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising characteristic peaks expressed in degrees 2θ at 6.918 and 8.000.
69. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 2-propyl alcohol solvate according to claim 68 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 8.619.
70. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 2-propyl alcohol solvate according to claim 68 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 18.162.
71. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 2-propyl alcohol solvate according to claim 68 exhibits an x-ray powder diffraction pattern comprising at least one peak expressed in degrees 2θ at 8.619, 11.338, 11.718, 12.241, 15.382, 18.162, or 20.779.
72. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-butyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 7.060.
73. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-butyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 9.078.
74. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-butyl alcohol solvate that exhibits an x-ray powder diffraction pattern comprising characteristic peaks expressed in degrees 2θ at 7.060 and 9.078.
75. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt 1-butyl alcohol solvate according to claim 74 that exhibits an x-ray powder diffraction pattern comprising at least one peak expressed in degrees 2θ at 11.100, 16.361, 18.040, 18.820, 19.922, 21.560, 22.281, or 23.521.
76. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 2 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 7.259.
77. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 2 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 8.739.
78. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 2 that exhibits an x-ray powder diffraction pattern comprising characteristic peaks expressed in degrees 2θ at 7.259 and 8.739.
79. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 2 according to claim 78 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 17.361.
80. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2.2-dimethylhexanoic acid monocalcium salt Crystal Form 2 according to claim 78 that exhibits an x-ray powder diffraction pattern comprising a characteristic peak expressed in degrees 2θ at 18.063.
81. The compound 6-(5-carboxy-5-methyl-hexyloxy)-2,2-dimethylhexanoic acid monocalcium salt Crystal Form 2 according to claim 78 that exhibits an x-ray powder diffraction pattern comprising at least one peak expressed in degrees 2θ at 9.386, 11.659, 13.955, 14.220, 15.387, 16.461, 17.361, 18.063, 19.302, 19.862, 20.200, 21.178, 21.641, 22.300, 23.218, 24.100, 25.481, 28.800, 29.297, or 30.700.