Isostructural pseudopolymorphs of 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A

Related U.S. Application Data

(60) Provisional application No. 60/394,705, filed on Jul. 8, 2002, provisional application No. 60/393,612, filed on Jul. 3, 2002.

(30) Foreign Application Priority Data

Mar. 18, 2002 (HR) P 20020231 A

(51) Int. CI.

A61K 31/70 (2006.01)
C07H17/08 (2006.01)

(52) U.S. CI 514/29; 536/7.4

(58) Field of Classification Search 537/7.4;

536/18.5,7.4; 514/29 See application file for complete search history.

(56) References Cited

U.S. PATENT DOCUMENTS

4,517,359 A 5/1985 Kobrehel et al.

6,420,537 Bl * 7/2002 Bosch et al 536/7.4

6,528,492 Bl 3/2003 de la Torre Garcia et al.

6,586,576 B2 7/2003 Aronhime et al.

6,703,372 Bl* 3/2004 Centellas et al 514/29

6,861,413 B2 3/2005 Lietal.

6,949,519 B2* 9/2005 Centellas et al 514/29

6,977,243 B2 * 12/2005 Lietal 514/29

7,309,782 B2 12/2007 Lietal.

2003/0139583 Al 7/2003 Singh etal.

2003/0162730 Al 8/2003 Lietal.

2003/0165563 Al 9/2003 Murphy etal.

2003/0190365 Al 10/2003 Fergione et al.

CN CN

116971 1205338

10/1997 1/1999

(Continued)

OTHER PUBLICATIONS

Ognjen Culic et al., Anti-inflammatory effects of macrolide antibiotics, European Journal of Pharmacology 429:209-229 (2001). Ognjen Culic et al., Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects, European Journal of Pharmaclogy 450:277-289 (2002).

(Continued)

Primary Examiner—Elli Peselev

(74) Attorney, Agent, or Firm—Sterne Kessler Goldstein & Fox, PLLC

(57)

ABSTRACT

Substantially pure isostructural pseudopolymorphs of 9-deoxo-9a-aza-9a-methyl-9a-homoerythromycin A having the Formula I:

(I)

[H20]x [S]y

wherein S is an organic solvent which is at least partially miscible with water, x is 1, 1.25, 1.5 or 2, y is 0, 0.5, or 1, the pseudopolymorph being characterized by the monoclinic space group ~P2l and average unit cell parameters comprising: crystal axis lengths of a=15.5-17.0 A, b=15.5-17.0 A, and c=17.5-19.5 A, and angles between the crystal axes of a=y=90° and (3=106°-112°. In addition, this disclosure is directed to processes for the preparation of the substantially pure isostructural pseudopolymorphs of Formula I; to pharmaceutical compositions containing substantially pure isostructural pseudopolymorphs of Formula I; and to a method for the treatment of bacterial and protozoan infections, and inflammation-related diseases by administration of a pharmaceutical composition containing the substantially pure isostructural pseudopolymorphs of Formula I.

6 Claims, 23 Drawing Sheets