Crystalline forms of the mono-sodium salt of D-isoglutamyl-D-tryptophan
The present invention relates to crystalline forms of the mono-sodium salt of D-isoglutamyl-D-tryptophan, pharmaceutical compositions comprising them, their use in the treatment of various diseases and conditions, and processes for their preparation. In particular, the present invention relates the crystal modification 1 (polymorphic form F) of the mono-sodium salt of D-isoglutamyl-D-tryptophan.
1. A crystalline mono-sodium salt of D-isoglutamyl-D-tryptophan, wherein the crystalline material is crystal modification 1 (polymorphic form F).
2. The crystal modification 1 (polymorphic form F) of the mono sodium salt of D-isoglutamyl-D-tryptophan of claim 1 , having a XRPD pattern as shown in FIG. 2 .
3. The crystal modification 1 (polymorphic form F) of the mono sodium salt of D-isoglutamyl-D-tryptophan of claim 1 , having an XRPD pattern comprising peaks, in terms of 2θ, at: 9.23±0.20, 9.91±0.20, 12.41±0.20, 13.76±0.20, 14.87±0.20, 15.75±0.20, 17.88±0.20, 18.78±0.20, 19.57±0.20, 19.84±0.20, 20.31±0.20, 21.32±0.20, 21.55±0.20, 22.95±0.20, 23.45±0.20, 24.34±0.20, 24.96±0.20, 27.49±0.20, 27.94±0.20, 29.27±0.20, 30.07±0.20, 30.43±0.20, 31.29±0.20, 32.25±0.20, 34.07±0.20, 34.94±0.20, 35.53±0.20, 36.08±0.20, 37.21±0.20, 38.17±0.20, 39.19±0.20, and 9.23±0.20.
4. The crystal modification 1 (polymorphic form F) of the mono sodium salt of D-isoglutamyl-D-tryptophan of claim 1 , having an XRPD pattern comprising peaks, in terms of 2θ, at: 9.23±0.10, 9.91±0.10, 12.41±0.10, 13.76±0.10, 14.87±0.10, 15.75±0.10, 17.88±0.10, 18.78±0.10, 19.57±0.10, 19.84±0.10, 20.31±0.10, 21.32±0.10, 21.55±0.10, 22.95±0.10, 23.45±0.10, 24.34±0.10, 24.96±0.10, 27.49±0.10, 27.94±0.10, 29.27±0.10, 30.07±0.10, 30.43±0.10, 31.29±0.10, 32.25±0.10, 34.07±0.10, 34.94±0.10, 35.53±0.10, 36.08±0.10, 37.21±0.10, 38.17±0.10, 39.19±0.10, and 9.23±0.10.
5. The crystal modification 1 (polymorphic form F) of the mono sodium salt of D-isoglutamyl-D-tryptophan of claim 1 , having an XRPD pattern measured using a diffractometer (copper anti-cathode) and expressed in terms of inter-planar distances d, Bragg's angle 2 theta, and relative intensity (expressed as a percentage with respect to the most intense ray) as follows:
2-Theta
D-spacing
Relative Intensity
(°)
(Angstrom)
(%)
9.23
9.573
2
9.91
8.917
41.3
12.41
7.126
37.6
13.76
6.43
0.8
14.87
5.954
35.8
15.75
5.622
7.6
17.88
4.957
5.5
18.78
4.721
58.9
19.57
4.532
30.9
19.84
4.471
28.1
20.31
4.368
2.9
21.32
4.165
53.5
21.55
4.12
30.3
22.95
3.873
67.4
23.45
3.79
24.5
24.34
3.654
19.4
24.96
3.565
85.2
27.49
3.242
100
27.94
3.19
23.3
29.27
3.049
19.1
30.07
2.97
27.2
30.43
2.935
15.2
31.29
2.856
39.9
32.25
2.774
13
34.07
2.629
19.3
34.94
2.566
7.8
35.53
2.525
5
36.08
2.487
8.4
37.21
2.414
15.5
38.17
2.356
9.1
39.19
2.297
3.1.
6. The crystalline mono-sodium salt of D-isoglutamyl-D-tryptophan of claim 1 , wherein the crystalline material is a mixture of the crystal modification 1 (polymorphic form F) and the crystal modification 2 (polymorphic form I) of the mono sodium salt of D-isoglutamyl-D-tryptophan.
7. The crystalline mono-sodium salt of D-isoglutamyl-D-tryptophan of claim 1 , having an X-ray powder diffraction pattern comprising peaks of relative intensity over 50% at 2θ angles of approximately 18.78, 21.32, 22.95, 24.96 and 27.49 degrees.
8. A pharmaceutical composition comprising the crystalline mono-sodium salt of D-isoglutamyl-D-tryptophan of any one of claims 1 to 7 and at least one pharmaceutically acceptable carrier.
9. A pharmaceutical composition comprising the crystalline mono-sodium salt of D-isoglutamyl-D-tryptophan of claim 1 , and at least one pharmaceutically acceptable carrier, wherein the crystalline material is a mixture of crystal modification 1 (polymorphic form F) and crystal modification 3 (polymorphic form X) of the mono-sodium salt of D-isoglutamyl-D-tryptophan.
10. A method of treating an auto-immune disease, the method comprising administration of an effective amount of a pharmaceutical composition according to claim 8 to a subject in need thereof, wherein the auto-immune disease is selected from the group consisting of psoriasis, atopic dermatitis and rheumatoid arthritis.
11. A method of treating an auto-immune disease, the method comprising administration of an effective amount of a pharmaceutical composition according to claim 9 to a subject in need thereof, wherein the auto-immune disease is selected from the group consisting of psoriasis, atopic dermatitis and rheumatoid arthritis.