Methods of treatment of cancer by continuous infusion of coenzyme Q10

Patent metadata

Field	Value
Publication number	US-11298313-B2
Application number	US-201815869630-A
Country	US
Kind code	B2
Filing date	Jan 12, 2018
Priority date	Sep 4, 2013
Publication date	Apr 12, 2022
Grant date	Apr 12, 2022

Abstract

The invention provides regimens and methods for the treatment of cancer comprising continuous infusion of coenzyme Q10. The coenzyme Q10 may be administered as a monotherapy, or in combination with an additional agent, such as an anticancer agent, a chemotherapeutic agent, or an anti-angiogenic agent. The coenzyme Q10 may be administered at two or more different rates.

First claim

The invention claimed is:

1. A method of treating cancer in a subject, comprising administering a composition comprising from 0.001% to 20% (w/w) of coenzyme Q10 by continuous intravenous infusion for at least 48 hours, thereby treating the cancer in the subject.

2. The method of claim 1 , wherein the coenzyme Q10 is administered at two or more different rates.

3. The method of claim 2 , wherein the coenzyme Q10 is administered sequentially at a first rate and a second rate, wherein the first rate is higher than the second rate.

4. The method of claim 3 , further comprising administration of coenzyme Q10 at a third rate after the second rate.

5. The method of claim 4 , wherein the third rate is lower than the first rate and higher than the second rate.

6. The method of claim 3 , wherein the coenzyme Q10 is administered at the first rate for about 0.5 hours to about 3 hours.

7. The method of claim 3 , wherein the total time of the infusion at the first rate plus the time of the infusion at the second rate is about 24 hours, about 48 hours, or about 72 hours.

8. The method of claim 2 , wherein the coenzyme Q10 is administered by continuous intravenous infusion for at least 72 hours, at least 96 hours, or at least 144 hours.

9. The method of claim 3 , wherein the first rate is no more than 3.1 mg/kg/hr, no more than 4.2 mg/kg/hour, no more than 5.5 mg/kg/hour, no more than 7.4 mg/kg/hour, no more than 8.3 mg/kg/hour, no more than 9.2 mg/kg/hour, no more than 11.0 mg/kg/hour, no more than 11.2 mg/kg/hour, no more than 14 mg/kg/hour, no more than 14.5 mg/kg/hour, no more than 18.0 mg/kg/hour, no more than 18.4 mg/kg/hour, no more than 19.6 mg/kg/hour, no more than 22.9 mg/kg/hour, no more than 26.0 mg/kg/hour, no more than 28.7 mg/kg/hour, or no more than 35.8 mg/kg/hour.

10. The method of claim 1 , further comprising
(a) monitoring the subject for decreased coagulation; and
(b) discontinuing treatment with coenzyme Q10 in a subject identified as having decreased coagulation.

11. The method of claim 1 , further comprising
(a) monitoring the subject for decreased coagulation;
(b) administering an agent to increase coagulation in a subject identified as having decreased coagulation;
(c) confirming the subject has normal coagulation; and
(d) continuing treatment with coenzyme Q10.

12. The method of claim 1 , further comprising
(a) monitoring the subject for decreased coagulation; and
(b) continuing treatment with coenzyme Q10 in a subject identified as having normal coagulation.

13. A method of preventing or limiting severity of an adverse event associated with treatment of cancer with intravenously administered coenzyme Q10, comprising administering to a subject having cancer a composition comprising from 0.001% to 20% (w/w) of coenzyme Q10 by continuous intravenous infusion for at least 48 hours, wherein the severity of the adverse event in the subject is reduced as compared to intravenous administration of the same dose of coenzyme Q10 over a period of 6 hours or less.

14. The method of claim 13 , wherein the adverse event comprises a coagulopathy.

15. The method of claim 13 , wherein the adverse event comprises a bleeding event.

16. The method of claim 1 , wherein the composition comprising coenzyme Q10 is administered by continuous intravenous infusion for about 96 hours, and wherein the composition is administered sequentially at a first rate, a second rate, and a third rate wherein:
(a) the first rate is a highest rate administered during the first hour of the continuous intravenous infusion;
(b) the second rate is a lowest rate administered during hours 2 to 48 of the continuous intravenous infusion; and
(c) the third rate is an intermediate rate between the first rate and the second rate and is administered during hours 49 to 96 of the continuous intravenous infusion.

17. The method of claim 1 , wherein the composition comprising coenzyme Q10 is administered by continuous intravenous infusion for about 144 hours, and wherein the composition is administered sequentially at a first rate, a second rate, and a third rate wherein:
(a) the first rate is a highest rate administered during the first hour of the continuous intravenous infusion;
(b) the second rate is a lowest rate administered during hours 2 to 72 of the continuous intravenous infusion; and
(c) the third rate is an intermediate rate between the first rate and the second rate and is administered during hours 73 to 144 of the continuous intravenous infusion.

18. The method of claim 16 , wherein the first rate is selected from the group consisting of no more than 3.1 mg/kg/hour, no more than 4.2 mg/kg/hour, no more than 5.5 mg/kg/hour, no more than 7.4 mg/kg/hour, no more than 8.3 mg/kg/hour, no more than 9.2 mg/kg/hour, no more than 11.0 mg/kg/hour, no more than 11.2 mg/kg/hour, no more than 14.0 mg/kg/hour, no more than 14.5 mg/kg/hour, no more than 18.0 mg/kg/hour, no more than 18.4 mg/kg/hour, no more than 19.6 mg/kg/hour, no more than 22.9 mg/kg/hour, no more than 26.0 mg/kg/hour, no more than 28.7 mg/kg/hour, and no more than 35.8 mg/kg/hour.

19. The method of claim 16 , wherein the coenzyme Q10 is administered at a dose selected from the group consisting of about 50 mg/kg/48 hour infusion and the first rate is about 4.2 mg/kg/hour, about 66 mg/kg/48 hour infusion and the first rate is about 5.5 mg/kg/hour, about 88 mg/kg/48 hour infusion and the first rate is about 7.4 mg/kg/hour, about 110 mg/kg/48 hour infusion and the first rate is about 9.2 mg/kg/hour, about 137 mg/kg/48 hour infusion and the first rate is about 11 mg/kg/hour, about 171 mg/kg/48 hour infusion and the first rate is about 14 mg/kg/hour, about 215 mg/kg/48 hour infusion and the first rate is about 18 mg/kg/hour, and about 40 mg/kg/48 hour infusion to about 250 mg/kg/48 hour infusion and the first rate is about 3.4 mg/kg/hour to about 21 mg/kg/hour.

20. The method of claim 17 , wherein the coenzyme Q10 is administered at a dose selected from the group consisting of about 38 mg/kg/72 hour infusion and the first rate is about 3.1 mg/kg, about 50 mg/kg/72 hour infusion and the first rate is about 4.1 mg/kg/hour, about 66 mg/kg/72 hour infusion and the first rate is about 5.4 mg/kg/hour, about 88 mg/kg/72 hour infusion and the first rate is about 7.2 mg/kg/hour, about 110 mg/kg/72 hour infusion and the first rate is about 9.0 mg/kg/hour, about 137 mg/kg/72 hour infusion and the first rate is about 11.2 mg/kg/hour, about 171 mg/kg/72 hour infusion and the first rate is about 14.0 mg/kg/hour, about 215 mg/kg/72 hour infusion and the first rate is about 17.6 mg/kg/hour, and about 38 mg/kg/72 hour infusion to about 250 mg/kg/72 hour infusion and the first rate is about 3.1 mg/kg/hour to about 21 mg/kg/hour.

21. The method of claim 1 , wherein the composition comprising coenzyme Q10 is administered by continuous intravenous infusion for about 18 days, and wherein the composition is administered sequentially at a first rate, a second rate, and a third rate wherein:
(a) the first rate is a highest rate administered during hour 1 of day 1 of the continuous infusion;
(b) the second rate is a lowest rate administered during hours 2 to 24 of day 1 of the continuous infusion; and
(c) the third rate comprises an intermediate rate administered between the first rate and the second rate administered during days 2 to 17 of the continuous infusion.

22. The method of claim 13 , wherein the first rate is a rate selected from the group consisting of no more

Assignees

• Berg Llc

Inventors

• Narain Niven Rajin
• Sarangarajan Rangaprasad
• Gray Thomas Mitchell
• Mccook John Patrick
• Jimenez Joaquin J

Classifications

• A61K9/0019 Primary

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• A61K31/704

  attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} · CPC title

• A61K31/7068

  having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid · CPC title

• A61K31/122 Primary

  having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin · CPC title