Claims
- 1. Two polymorphs of (2R,3S,4R,5R,8R,10R,11R,12S,13S,14R)-13-[[2,6-dideoxy-3-C-methyl-3-O-methyl-4-C-[(propylamino)methyl]-α-L-ribo-hexopryanosyl]oxy]-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D-xylo-hexopyranosyl]oxy]-1-oxa-6-azacyclopentadecan-15-one diphosphate having the formula wherein n is 0 to 8 and the polymorphs are selected from the group consisting of:a. a smectic crystalline meso phase of a liquid crystal; and b. a crystalline diphosphate exhibiting the X-ray powder diffraction pattern Peak No.12345678910d space16.212.410.89.06.96.56.25.45.14.9
- 2. The diphosphate liquid crystal according to claim 1 having a lath-like habit and exhibiting longitudinal cleavage.
- 3. The diphosphate liquid crystal according to claim 2 gaining about 15% by weight with a subsequent loss of birefringence at about 87% relative humidity.
- 4. The diphosphate salt according to claim 2, wherein the liquid crystal has about 5 to 6% water.
- 5. The diphosphate salt according to claim 1 wherein the salt has about 48% C, about 9% H, about 4% N, about 6% P and about 5.5% H2O.
- 6. The diphosphate salt polymorph according to claim 1 having a well-ordered crystalline plate or prism habit.
- 7. The diphosphate salt according to claim 6 wherein the plate or prism habit is highly birefringent.
- 8. The crystalline diphosphate salt according to claim 1, wherein the compound gradually absorbs water to about 13% at about 87% relative humidity.
- 9. The diphosphate salt according to claim 8, wherein a rapid uptake of water to about 48% occurs at about 90% relative humidity.
- 10. The diphosphate salt according to claim 9 wherein the diphosphate salt became deliquescent at about 90% relative humidity.
- 11. The diphosphate salt according to claim 1 wherein thermogravametric analysis discloses that 3 waters are lost by about 75° C., a fourth water is lost by about 120° C., a fifth water is lost by about 170° C., and the three final waters are lost by about 200° C.
- 12. The diphosphate salt according to claim 1 wherein the maximum number of water molecules necessary for the stabilization of the crystalline lattice is eight.
- 13. The diphosphate salt according to claim 1 wherein drying in about 70° C. in air or about 45° C. in a vacuum removed the water leaving a psuedomorph.
- 14. The diphosphate salt according to claim 1 wherein the aqueous solubility is about 280 mg/mL.
- 15. A pharmaceutical composition having antibacterial and antiprotozoal activity in mammals comprising the free base of the diphosphate salt according to claim 1 in an amount effective in the treatment of bacterial and protozoal diseases and a pharmaceutically acceptable carrier.
Parent Case Info
This application claims the benefit of U.S. Provisional Patent Application No. 60/141,681 filed Jun. 30, 1999.
Foreign Referenced Citations (1)
Number |
Date |
Country |
WO 9856802 |
Dec 1998 |
WO |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/141681 |
Jun 1999 |
US |