Granted Patent B2

US 11,878,021 · App. 17/355,336 · Granted Jan 23, 2024

Inventors: Claude Michel Wischik (Aberdeen, GB); John Mervyn David Storey (Old Aberdeen, GB); Colin Marshall (Old Aberdeen, GB); James Peter Sinclair (Old Aberdeen, GB); Thomas Craven Baddeley (Old Aberdeen, GB)

Assignee: WisTa Laboratories Ltd.

A61K31/5415C07D279/18C07D279/20Y02A50/30

Abstract

Claims (107)

1. A high-purity diaminophenothiazinium compound of the following formula:

wherein:

each of R 1 and R 9 is independently —H, C 1-4 alkyl, C 2-4 alkenyl, or halogenated C 1-4 alkyl;

each of R 3NA and R 3NB is independently C 1-4 alkyl, C 2-4 alkenyl, or halogenated C 1-4 alkyl;

each of R 7NA and R 7NB is independently C 1-4 alkyl, C 2-4 alkenyl, or halogenated C 1-4 alkyl; and

X is one or more anionic counter ions to achieve electrical neutrality; and wherein high-purity is characterized by:

a purity of greater than 98%;

less than 1% Azure B as impurity;

less than 100 μg/g Aluminium (Al);

less than 1 μg/g Cadmium (Cd);

less than 100 μg/g Chromium (Cr);

less than 300 μg/g Copper (Cu);

less than 10 μg/g Tin (Sn);

less than 200 μg/g Iron (Fe);

less than 10 μg/g Manganese (Mn);

less than 1 μg/g Mercury (Hg);

less than 10 μg/g Molybdenum (Mo);

less than 10 μg/g Nickel (Ni);

less than 10 μg/g Lead (Pb); and

less than 100 μg/g Zinc (Zn).

2. The compound of claim 1 , wherein the high-purity diaminophenothiazinium compound has the formula:

3. The compound of claim 1 , wherein the high-purity diaminophenothiazinium compound has:

less than 50 μg/g Aluminium (Al);

less than 0.5 μg/g Cadmium (Cd);

less than 50 μg/g Chromium (Cr);

less than 150 μg/g Copper (Cu);

less than 5 μg/g Tin (Sn);

less than 100 μg/g Iron (Fe);

less than 5 μg/g Manganese (Mn);

less than 0.5 μg/g Mercury (Hg);

less than 5 μg/g Molybdenum (Mo);

less than 5 μg/g Nickel (Ni);

less than 5 μg/g Lead (Pb); and

less than 50 μg/g Zinc (Zn).

4. The compound of claim 2 , wherein the high-purity diaminophenothiazinium compound has:

less than 50 μg/g Aluminium (Al);

less than 0.5 μg/g Cadmium (Cd);

less than 50 μg/g Chromium (Cr);

less than 150 μg/g Copper (Cu);

less than 5 μg/g Tin (Sn);

less than 100 μg/g Iron (Fe);

less than 5 μg/g Manganese (Mn);

less than 0.5 μg/g Mercury (Hg);

less than 5 μg/g Molybdenum (Mo);

less than 5 μg/g Nickel (Ni);

less than 5 μg/g Lead (Pb); and

less than 50 μg/g Zinc (Zn).

5. The compound of claim 1 , wherein the high-purity diaminophenothiazinium compound has a purity of greater than 99%.

6. The compound of claim 2 , wherein the high-purity diaminophenothiazinium compound has a purity of greater than 99%.

7. The compound of claim 1 , wherein the high-purity diaminophenothiazinium compound has:

less than 0.15% Azure A as impurity;

less than 0.15% Azure C as impurity; and

less than 0.05% Methylene Violet Bernthsen (MVB) as impurity.

8. The compound of claim 2 , wherein the high-purity diaminophenothiazinium compound has:

less than 0.15% Azure A as impurity;

less than 0.15% Azure C as impurity; and

less than 0.05% Methylene Violet Bernthsen (MVB) as impurity.

9. The compound of claim 1 , wherein the high-purity diaminophenothiazinium compound has less than 0.5% Azure B as impurity.

10. The compound of claim 2 , wherein the high-purity diaminophenothiazinium compound has less than 0.5% Azure B as impurity.

11. An aqueous solution of a high-purity diaminophenothiazinium compound comprising

(a) the high-purity diaminophenothiazinium compound of claim 1 ; and

(b) an aqueous isotonic, pyrogen-free, sterile liquid in which the high-purity diaminophenothiazinium compound is dissolved.

12. The aqueous solution of claim 11 , wherein the high-purity diaminophenothiazinium compound has the formula:

13. The aqueous solution of claim 11 , wherein the aqueous isotonic, pyrogen-free, sterile liquid is selected from Sodium Chloride Injection, Ringer's Solution, or Lactated Ringer's Injection.

14. The aqueous solution of claim 12 , wherein the aqueous isotonic, pyrogen-free, sterile liquid is selected from Sodium Chloride Injection, Ringer's Solution, or Lactated Ringer's Injection.

15. The aqueous solution of claim 11 , presented in a unit-dose sealed container.

16. The aqueous solution of claim 12 , presented in a unit-dose sealed container.

17. The aqueous solution of claim 15 , in a dose form for injection.

18. The aqueous solution of claim 16 , in a dose form for injection.

19. The aqueous solution of claim 11 , wherein the high-purity diaminophenothiazinium compound has:

less than 50 μg/g Aluminium (Al);

less than 0.5 μg/g Cadmium (Cd);

less than 50 μg/g Chromium (Cr);

less than 150 μg/g Copper (Cu);

less than 5 μg/g Tin (Sn);

less than 100 μg/g Iron (Fe);

less than 5 μg/g Manganese (Mn);

less than 0.5 μg/g Mercury (Hg);

less than 5 μg/g Molybdenum (Mo);

less than 5 μg/g Nickel (Ni);

less than 5 μg/g Lead (Pb); and

less than 50 μg/g Zinc (Zn).

20. The aqueous solution of claim 12 , wherein the high-purity diaminophenothiazinium compound has:

less than 50 μg/g Aluminium (Al);

less than 0.5 μg/g Cadmium (Cd);

less than 50 μg/g Chromium (Cr);

less than 150 μg/g Copper (Cu);

less than 5 μg/g Tin (Sn);

less than 100 μg/g Iron (Fe);

less than 5 μg/g Manganese (Mn);

less than 0.5 μg/g Mercury (Hg);

less than 5 μg/g Molybdenum (Mo);

less than 5 μg/g Nickel (Ni);

less than 5 μg/g Lead (Pb); and

less than 50 μg/g Zinc (Zn).

21. The aqueous solution of claim 11 , wherein the high-purity diaminophenothiazinium compound has a purity of greater than 99%.

22. The aqueous solution of claim 12 , wherein the high-purity diaminophenothiazinium compound has a purity of greater than 99%.

23. The aqueous solution of claim 11 , wherein the high-purity diaminophenothiazinium compound has:

less than 0.15% Azure A as impurity;

less than 0.15% Azure C as impurity; and

less than 0.05% Methylene Violet Bernthsen (MVB) as impurity.

24. The aqueous solution of claim 12 , wherein the high-purity diaminophenothiazinium compound has:

less than 0.15% Azure A as impurity;

less than 0.15% Azure C as impurity; and

less than 0.05% Methylene Violet Bernthsen (MVB) as impurity.

25. The aqueous solution of claim 11 , wherein the high-purity diaminophenothiazinium compound has less than 0.5% Azure B as impurity.

26. The aqueous solution of claim 12 , wherein the high-purity diaminophenothiazinium compound has less than 0.5% Azure B as impurity.

Assignments (3)

Continuity (9)