Tuberculosis drug based on 4-thioureido-iminomethylpyridinium perchlorate: method of preparation andtreatment

1. A composition, comprising:

a therapeutically effective and safe amount of an active ingredient, wherein the active ingredient is 4-thioureido-iminomethylpyridinium perchlorate, wherein 4-thioureido-iminomethylpyridinium perchlorate is in amount of 5.0 to 90.0% w/w of the composition; and

at least one additional pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient is up to 100% w/w of the composition.

2. The composition of claim 1 , wherein 4-thioureido-iminomethylpyridinium perchlorate is between 10 mg and 1000 mg.

3. The composition of claim 3 , wherein 4-thioureido-iminomethylpyridinium perchlorate is between 10 mg and 30 mg.

4. The composition of claim 1 , wherein the at least one additional pharmaceutically acceptable excipients is selected from the group consisting of sucrose, povidone, microcrystalline cellulose, colloidal silicon dioxide, and ethylcellulose.

5. The composition of claim 4 , wherein

the sucrose is in an amount of 3.1 to 50.4% w/w of the composition;

the povidone is in an amount of 0.9 to 14.4% w/w of the composition;

the microcrystalline cellulose is in an amount of 1.1 to 18.0% w/w of the composition;

the colloidal silicon dioxide is in an amount of 0.2 to 3.6% w/w of the composition; or

the ethylcellulose is in an amount of 0.2 to 3.6% w/w of the composition.

6. The composition of claim 1 , further comprising:

a coating comprising copolymers of methacrylic acid and ethyl acrylate, triethyl citrate, macragol, talc, and ferric oxide dye, wherein

the methacrylic acid and ethyl acrylate copolymer is in an amount of 3.0 to 4.0% w/w of the composition;

triethyl acetate is in an amount of 0.8 to 1.8% w/w of the composition;

macragol is in an amount of 0.2 to 0.4% w/w of the composition;

talc is in an amount of 0.9 to 1.3% w/w of the composition; and

ferric oxide dye is in an amount of 0.2 and 0.3% w/w of the composition.

7. The composition of claim 1 , further comprising:

at least one additional tuberculosis agent in an amount of not more than 90% w/w of the composition.

8. The composition of 7, wherein the additional tuberculosis agents are selected from the group consisting of isoniazid, pyrazinamid, rifampicin, rifabutin, amycacin, ethambutol, and fluoroquinolone antibiotic.

9. The composition of 8, wherein

the 4-thioureido-iminomethylpyridinium perchlorate is between 10 mg and 1000 mg; and

the isoniazid is at between 10 mg and 500 mg, the rifampicin is at between 10 mg and 667 mg, the rifabutin is at between 8.5 mg and 284 mg, the amycacin is at between 20 mg and 667 mg, the ethambutol is at between 20 mg and 667 mg, or the ofloxacin is at between 20 mg and 667 mg.

10. The composition of claim 1 , wherein the composition is in a form selected from the group consisting of film-coated tablets, combined tablets, capsules, granules, suppositories, and suspensions.

11. A method of preparing a composition comprising a therapeutically safe and effective amount of 4-thioureido-iminomethylpyridinium perchlorate and at least one pharmaceutically acceptable excipient, the method comprising the steps of:

providing 4-thioureido-iminomethylpyridinium perchlorate and the excipient in powder form;

sieving and mixing the 4-thioureido-iminomethylpyridinium perchlorate and the excipient to form a mixture;

forming a granule from the mixture comprising:

subjecting the mixture to wet granulation;

drying the granule;

dusting the granule,

forming tablet core by pressing the granule; and

film-coating the tablet core through aqueous suspension.

12. The method of claim 11 , wherein the wet granulation uses a solution of povidone and sugar syrup.

13. The method of claim 11 , wherein 4-thioureido-iminomethylpyridinium perchlorate is between 10 mg and 1000 mg.

14. The method of claim 11 , wherein the at least one pharmaceutically acceptable excipients is selected from the group consisting of sucrose, povidone, microcrystalline cellulose, colloidal silicon dioxide, and ethylcellulose, wherein

the sucrose is in an amount of 3.1 to 50.4% w/w of the composition;

the povidone is in an amount of 0.9 to 14.4% w/w of the composition;

the microcrystalline cellulose is in an amount of 1.1 to 18.0% w/w of the composition;

the colloidal silicon dioxide is in an amount of 0.2 to 3.6% w/w of the composition; and

the ethylcellulose is in an amount of 0.2 to 3.6% w/w of the composition.

15. The method of claim 11 , further comprising:

providing at least one additional tuberculosis agent in an amount of not more than 90% w/w of the composition, wherein the additional tuberculosis agents are selected from the group consisting of isoniazid, pyrazinamid, rifampicin, rifabutin, amycacin, ethambutol, and fluoroquinolone antibiotic.

16. The method of claim 15 , wherein the isoniazid is at between 10 mg and 500 mg, the rifampicin is at between 10 mg and 667 mg, the rifabutin is at between 8.5 mg and 284 mg, the amycacin is at between 20 mg and 667 mg, the ethambutol is at between 20 mg and 667 mg, or the ofloxacin is at between 20 mg and 667 mg.

17. The method of claim 11 , wherein the tablet core is film-coated by the method comprising the steps:

providing a coating solution comprising copolymers of methacrylic acid and ethyl acrylate, triethyl citrate, macragol, talc, and ferric oxide dye, wherein

the methacrylic acid and ethyl acrylate copolymer is in an amount of 3.0 to 4.0% w/w of the composition;

the triethyl acetate is in an amount of 0.8 to 1.8% w/w of the composition;

the macragol is in an amount of 0.2 to 0.4% w/w of the composition;

the talc is in an amount of 0.9 to 1.3% w/w of the composition;

the ferric oxide dye is in an amount of 0.2 and 0.3% w/w of the composition;

placing the tablet core into the coating solution or placing the tablet core under running coating solution; and

allowing the coating solution to dry or cure.

18. A method of treating and preventing pulmonary and extrapulmonary tuberculosis, the method comprising the step of:

administering a composition in a therapeutically effective amount to a patient in need thereof,

wherein the composition comprises:

a therapeutically safe and effective amount of 4-thioureido-iminomethylpyridinium perchlorate; and

at least one pharmaceutically acceptable excipient.

19. The method of claim 18 , wherein the composition is administered by oral or parenteral route.

20. The method of claim 18 , wherein 4-thioureido-iminomethylpyridinium perchlorate is administered at between 10 mg/kg and 30 mg/kg.

21. The method of claim 18 , wherein the 4-thioureido-iminomethylpyridinium perchlorate is administered in a single daily dose of 20 mg/kg.

22. The method of 18, further comprising administering at least one additional tuberculosis agent, wherein the at least one additional tuberculosis agent is selected from the group consisting of isoniazid, pyrazinamid, rifampicin, rifabutin, amycacin, ethambutol, and fluoroquinolone antibiotic.

23. The method of claim 22 , wherein the isoniazid is administered at between 10 mg/kg and 15 mg/kg, the rifampicin is administered at between 10 mg/kg and 20 mg/kg, the rifabutin is administered at 8.5 mg/kg, the amycacin is administered at 20 mg/kg, the ethambutol is administered at 20 mg/kg, or the ofloxacin is administered at 20 mg/kg.