Patent EA-002953-B1 (EA)
Title: FORM VI 5,6-DOCHLORO-2-(ISOPROPYLAMINO)-1-(beta-L-RIBOFURANOSYL)-1H-BENZIMIDAZOLE
Inventor: CARTER BARRY HOWARD
IPC: A61P31/12
Filed: 1999-04-01
Abstract: 1. A crystalline form of VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole characterized by an X-ray powder diffraction pattern expressed in terms of 2 theta angles and obtained with a diffractometer equipped with a diffracted beam graphite monochromator using copper K.α-X-radiation, said X-ray powder diffraction pattern comprising 2 theta angle at five or more positions selected from the group consisting of 8.53 +-0.05, 10.47 +-0.05, 13.51 +-0.05, 14.95 +-0.05, 15.98 +-0.05, 17.23 +-0.05, 21.41 +-0.05, 21.83 +-0.05, 22.35 +-0.05, 23.07 +-0.05, and 27.49 +-0.05 degrees. 2. A composition comprising a crystalline form of VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole according to claim 1 and amorphous form of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole.  3. A pharmaceutical composition according to claim 1, comprising a crystalline form of VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole and at least one pharmaceutically acceptable carrier therefor. 4. Use of VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole according to claim 1 as a medicament. 5. Use of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole according to claim 1 in the preparation of a medicament for the treatment or prophylaxis of a viral infection. 6. A method according to claim 1 for the treatment or prophylaxis of a viral infection in a human which comprises administering to the human, an effective antiviral amount of a crystalline VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole. 7. A process for the production the crystalline form of VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole according to claim 1, comprising the addition of Form VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole to an aqueous suspension of Form II of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole, characterized by an X-ray powder diffraction pattern expressed in terms of 2 theta angles, d-spaces and a relative peak intensities (I): 2 Θ ( DEGREE )<1>	D ( ANGSTROM )<1>	I 7,91	11,17	100,0 10,86	8,14	10,1 12,69	6,97	5,2 13,65	6,48	4,7 14,94	5,93	8,4 16,11	5,50	12,8 17,33	5,11	17,5 18,23	4,86	18,2 19,60	4,53	19,6 21,88	4,06	18,8 23,24	3,82	19,0 23,92	3,72	26,7 25,27	3,52	24,5 27,70	3,22	34,9 29,21	3,06	14,2 error limit = +- 0,09 or to an aqueous suspension of the ethanol solvate of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole. 8. A process for the production of VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in anhydrous crystalline form VI, said process comprising the steps of: a) providing 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in solution either in free base or salt form; b) isolating 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole from the solution and optionally removing unbound solvent leaving the 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole in substantially dry form; c) treating 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole with a solubilising solvent serving to convert an amount of said optionally dried 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole into said VI 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole anhydrous crystalline form VI; and d) isolating said anhydrous crystalline form VI. 9. A process for the production the crystalline form of VI 5,6-dichloro-2-(isopropylamino)-1-β-L ribofuranosyl-1H-benzimidazole as claimed in any one of claims 1 to 4 comprising crystallization of 5,6-dichloro-2-(isopropylamino)-1-β-L-ribofuranosyl-1H-benzimidazole from a solution of ethyl acetate and toluene. 10. A pharmaceutical composition according to claim 3 in the form of a powder. 11. A pharmaceutical composition according to claim 3 in the form of a tablet. 12. A pharmaceutical composition according to claim 3 in the form of a capsule. 13. A pharmaceutical composition according to claim 3 in the form of a suspension.