SALTS AND POLYMORPHS OF A TETRACYCLINE COMPOUND
Crystalline forms, including salts and polymorphs, of a compound useful in the treatment of tetracycline compound-responsive states are provided herein. The crystalline compounds are useful for the treatment or prevention of conditions and disorders such as bacterial infections and neoplasms, as well as other known applications for tetracycline compounds in general.
1 . (canceled)
2 . A method of treating a tetracycline responsive state in a subject, comprising administering to the subject an effect amount of a tosylate salt of Compound 1:
selected from the group consisting of:
a polymorph characterized by an X-ray powder diffraction pattern including peaks at approximately 8.06, 13.02, and 18.83°2θ using Cu Kα radiation,
a polymorph characterized by an X-ray powder diffraction pattern including peaks at approximately 5.11 and 15.60°2θ using Cu Kα radiation, and
a polymorph characterized by an X-ray powder diffraction pattern including peaks at approximately 11.88 and 16.12°2θ using Cu Kα radiation.
3 - 5 . (canceled)
6 . The method of claim 1 , wherein the polymorph is characterized by an X-ray powder diffraction pattern including peaks at approximately 8.06, 11.41, 13.02, 18.83, 20.54, and 24.53°2θ using Cu Kα radiation.
7 . The method of claim 1 , wherein the polymorph is characterized by an X-ray powder diffraction pattern including peaks at approximately 5.60, 8.06, 8.57, 11.41, 13.02, 15.58, 18.83, 20.54 and 24.53°2θ using Cu Kα radiation.
8 . The method of claim 1 , wherein the polymorph is obtained by crystallizing the tosylate salt of Compound 1:
from isopropanol.
9 - 27 . (canceled)
28 . The method of claim 1 , wherein the polymorph of Compound 1 is administered as a pharmaceutical composition comprising said polymorph and a pharmaceutically acceptable diluent, excipient or carrier.
29 . The method of claim 28 wherein said polymorph is in a pure form.
30 . The method of claim 1 , wherein the polymorph is characterized by an X-ray diffraction pattern substantially similar to that set forth in FIG. 8 .
31 . The method of claim 1 , wherein the polymorph is characterized by an X-ray powder diffraction pattern including peaks at approximately 5.11, 8.89, 10.34, 11.76, and 15.60°2θ using Cu Kα radiation.
32 . The method of claim 1 , wherein the polymorph is characterized by an X-ray powder diffraction pattern including peaks at approximately 5.11, 8.89, 10.34, 11.76, 13.70, 14.81, and 15.60°2θ using Cu Kα radiation.
33 . The method of claim 1 , wherein the polymorph is characterized by an X-ray powder diffraction pattern substantially similar to that set forth in FIG. 10 .
34 . The method of claim 1 , wherein the polymorph is characterized by an X-ray powder diffraction pattern including peaks at approximately 7.82, 11.88, 16.12, and 21.46°2θ using Cu Kα radiation.
35 . The method of claim 1 , wherein the polymorph is characterized by an X-ray powder diffraction pattern including peaks at approximately 7.82, 11.88, 12.68, 16.12, 18.63, 21.46, and 23.74°2θ using Cu Kα radiation.
36 . The method of claim 1 , wherein the polymorph is characterized by an X-ray powder diffraction pattern substantially similar to that set forth in FIG. 9 .
37 . The method of claim 1 , wherein the polymorph is obtained by crystallizing the tosylate salt of Compound 1:
from a ketone.
38 . The method of claim 1 , wherein the polymorph is obtained by crystallizing the tosylate salt of Compound 1:
from acetone, methyl ethyl ketone or methyl pentanone.
39 . The method of claim 1 , wherein the polymorph is obtained by crystallizing the tosylate salt of Compound 1:
from ethyl acetate.
40 . The method of claim 1 , wherein the polymorph is obtained by crystallizing the tosylate salt of Compound 1:
from dichloromethane.
41 . The method of claim 1 , wherein tetracycline responsive state is a bacterial infection.
42 . The method of claim 41 , wherein the bacterial infection is associated with gram positive bacteria, or gram negative bacteria.
43 . The method of claim 41 , wherein the bacterial infection is associated E. coli, S. aureus , or E. faecalis.
44 . The method of claim 41 , wherein the bacterial infection is resistant to other tetracycline antibiotics.
45 . The method of claim 44 , wherein the other tetracycline antibiotics are selected from one or more of tetracycline, minocycline, doxycycline, sancycline, chlortetracycline, demeclocyclin, oxytetracycline, chelocardin, rolitetracycline, lymecycline, methacycline, apicycline, clomocycline, pipacycline, mepylcycline, meglucycline, guamecycline, penimocycline, or etamocycline.