TH69684A - Crystal and amorphous scaffolds of beta-L-2'-deoxithimidine. - Google Patents

Abstract

DC60 (06/09/56) reveals the physical construct of beta-L-2'-deoxythymidine, which can be identified by physical appearance, purity level, infrared and Raman spectroscopy, X-ray powder diffraction pattern, thermal properties, and methods of fabrication. These beta-L-2'-deoxythymidine constructs can be used to produce other beta-L-2'-deoxythymidine constructs or in pharmaceutical compositions. A particular application is in the treatment of hepatitis B. The physical construct of beta-L-2'-deoxythymidine, which can be identified by physical appearance, purity level, infrared and Raman spectroscopy, and X-ray powder diffraction pattern, is also revealed. X-ray powder diffraction, thermal properties, and methods for fabricating these beta-L-2'-deoxythimidine conformers can be used to produce other beta-L-2'-deoxythimidine conformers or in pharmaceutical compositions. A particularly promising application is in the treatment of hepatitis B.

Claims (35)

Updated 29/11/2018 1. Beta-L-2'-deoxythymidine (amorphous form) --------------------------------------------------- 1. Beta-L-2'-deoxythymidine in the amorphous form. 2. The solvent-free crystalline structure of beta-L-2'-deoxythimidine shows no significant amorphous beta-L-2'-deoxythimidine. 3. Amorphous beta-L-2'-deoxythimidine. 4. Amorphous beta-L-2'-deoxythimidine in a significantly purified construct. 5. A significantly purified phase of beta-L-2'-deoxythymidine was prepared by quench cooling of molten beta-L-2'-deoxythymidine. 6. Beta-L-2'-deoxythimidine of claim 1, prepared by crystallizing beta-L-2'-deoxythimidine from solution, may be selectively filtered and then dried in an environment containing approximately 40% relative humidity. 7. The physical crystalline structure of beta-L-2'-deoxythimidine is in the form of white flakes. 8. The physical crystal structure of beta-L-2'-deoxythimidine is in the form of transparent needles. 9. The physical crystal structure of beta-L-2'-deoxythimidine is in the form of white needles. 10. The physical crystalline structure of beta-L-2'-deoxythimidine as a white solid. 11. The physical crystalline structure of beta-L-2'-deoxythimidine in the form of a white powder. 12. The physical crystal structure of beta-L-2'-deoxythimidine is in the form of needle rods. 13. The physical crystalline structure of beta-L-2'-deoxythimidine in the form of white nodules. 14. The physical crystal structure of beta-L-2'-deoxythimidine is in the form of white plates. 15. The method for detecting amorphous contamination of beta-L-2'-deoxythymidine, or differentiating between crystalline and amorphous beta-L-2'-deoxythymidine, consists of: a) analyzing the material containing beta-L-2'-deoxythymidine by IR spectroscopy; b) evaluating the peak width, which is between 2200-2600, 1600-1800, 1000-1500, or 500-1000 cm⁻¹, by referencing known IR spectra for crystalline beta-L-2'-deoxythymidine. 16. Methods for detecting beta-L-2'-deoxythymidine contamination or differentiating between crystalline and amorphous beta-L-2'-deoxythymidine include: a) analyzing materials containing beta-L-2'-deoxythymidine by Raman spectroscopy; b) evaluating peak widths, which are between 2800-3200, 1600-1675, 1300-1500, or 700-900 cm⁻¹, by referencing known Raman spectra for crystalline beta-L-2'-deoxythymidine. 17. The method for producing pharmaceutical compounds of crystalline beta-L-2'-deoxythymidine involves: a) crystallizing two or more experimental sets of beta-L-2'-deoxythymidine from solution; b) analyzing these experimental sets using IR spectrometry; c) selecting experimental sets that do not show a clearly defined peak width for further processing between 2200-2600, 1600-1800, 1000-1500, or 500-1000 cm⁻¹ from known IR spectra for crystalline beta-L-2'-deoxythymidine; and d) preparing the compounds of the selected experimental sets into pharmaceutical compounds of beta-L-2'-deoxythymidine. 18. The method for producing pharmaceutical compounds of crystalline beta-L-2'-deoxythimidine involves: a) crystallization of two or more experimental sets of beta-L-2'-deoxythimidine from solution; b) analysis of these experimental sets using Raman spectrometry; c) selection of experimental sets that do not show a clearly defined peak width for further processing between 2800-3200, 1600-1675, 1300-1500, or 700-900 cm⁻¹ from known Raman spectra of crystalline beta-L-2'-deoxythimidine; and d) preparation of the selected experimental sets into pharmaceutical compounds of beta-L-2'-deoxythimidine. 19. A pharmaceutical formulation of crystalline beta-L-2'-deoxythimidine prepared by the procedure of Patent 17 or 18. 20. A method for forming a non-solvated crystalline form of anhydrous beta-L-2'-deoxythimidine, consisting of: a) crystallizing beta-L-2'-deoxythimidine from solution; b) possibly filtering the crystallized beta-L-2'-deoxythimidine; and c) drying the resulting beta-L-2'-deoxythimidine in an environment containing approximately less than 40% relative humidity. 21. A method for preparing significantly purified amorphous beta-L-2'-deoxythimidine, comprising: a) melting of beta-L-2'-deoxythimidine and b) quench cooling of the melt to avoid recrystallization. 22. The method of claim 21, which hereinafter involves cooling beta-L-2'-deoxythymidine to below approximately 50°C. 23. The method of claim 21, which hereafter includes maintaining relative humidity below approximately 20%. 24. A pharmaceutical mixture containing any compound or mixture of any of the claims under Sections 1-8, 13, 14, or 16-19, and a pharmacologically acceptable active ingredient. 25. The use of therapeutic doses of any of the compounds under claims 1-8, 13, 14, or 16-19 in the manufacture of drugs for the treatment of patients suffering from hepatitis B. 26. Beta-L-dT, which was significantly devoid of water for at least 4 months. 27. Beta-L-dT, which was significantly devoid of water for at least 6 months. 28. Beta-L-dT, which was significantly devoid of water for at least 8 months. 29. Beta-L-dT, which was significantly dehydrated for at least 10 months. 30. Beta-L-dT that is significantly devoid of water for at least 12 months. 31. A method for producing beta-L-dT is established by exposing the beta-L-dT to an environment with a relative humidity of no more than 10% for a period of at least 4 months, resulting in the L-dT being significantly dehydrated at the end of the 4-month period. 32. A method for producing beta-L-dT is established by exposing the L-dT to an environment with a relative humidity of no more than 20% for at least 4 months, resulting in the L-dT being free of significant water at the end of the 4-month period. 33. A method for producing beta-L-dT is established by exposing the L-dT to an environment with a relative humidity of no more than 30% for a period of at least 4 months, resulting in the L-dT being free of significant water at the end of the 4-month period. 34. The method of claim 33, hereafter incorporated, following a period of four months, involves the administration of the aforementioned L-dT to humans. 35. The use of any of the compounds listed in claims 1-14 or 26-30 in the manufacture of medicines for the treatment of patients suffering from hepatitis B.