Methods, compositions, and kits for treating and/or preventing a side effect associated with radiation and/or chemotherapy exposure

Patent metadata

Field	Value
Publication number	US-11285162-B2
Application number	US-201816500490-A
Country	US
Kind code	B2
Filing date	Apr 4, 2018
Priority date	Apr 4, 2017
Publication date	Mar 29, 2022
Grant date	Mar 29, 2022

Abstract

Described herein are methods, compositions, and kits for treating and/or preventing in a subject one or more side effects associated with radiation and/or chemotherapy exposure, including methods, compositions and kits that include an active agent at a low dose. In some embodiments, methods, compositions, and kits for treating and/or preventing tissue damage in a subject are provided, including methods, compositions and kits that include an active agent at a low dose.

First claim

That which is claimed is:

1. A method of treating and/or preventing one or more side effects associated with chemotherapy exposure in a subject during and/or following chemotherapy exposure, the method comprising:
administering to the subject prior to, during, or after chemotherapy exposure an active agent at a loading dose in an amount of about 0.05 mg/kg to about 1 mg/kg times the activity equivalent of BMX-001;
wherein the active agent is a meso-substituted metalloporphyrin.

2. The method of claim 1 , wherein the active agent is a superoxide dismutase (SOD) mimetic.

3. The method of claim 1 , wherein the active agent is a compound of Formula I:

wherein:
each R is independently selected from a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;
each A is an independently selected from a hydrogen, an electron-withdrawing group, or an electron donating group;
M is a metal; and
Z— is a counterion;

or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein the active agent has a structure of Formula A1:

wherein:
each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;
each A is, independently, hydrogen or an electron withdrawing group;
M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and
Z— is a counterion;
or a pharmaceutically acceptable salt thereof.

5. The method of claim 1 , wherein the active agent has a structure of Formula B1:

wherein:
each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;
each A is, independently, hydrogen or an electron withdrawing group;
M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and
Z— is a counterion;
or a pharmaceutically acceptable salt thereof.

6. The method of claim 1 , wherein said active agent has a structure of Formula C1:

wherein:
each R is, independently, hydrogen or —(CH 2 ) m CH 2 OX;
m is 1 or 2;
X is C1-12 alkyl;
each A is, independently, hydrogen or an electron withdrawing group;
M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and
Z— is a counterion;
or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 ,
wherein the active agent has the structure:

wherein Z − is a counterion; or a pharmaceutically acceptable salt thereof.

8. The method of claim 1 , wherein the loading dose is administered to the subject in an amount of about 0.1 mg/kg to about 0.6 mg/kg or about 0.1 mg/kg to about 0.6 mg/kg times the activity equivalent of BMX-001.

9. The method of claim 1 , wherein the loading dose is administered to the subject at about 30 minutes to about 4 days prior to the subject being exposed to the chemotherapy.

10. The method of claim 1 , wherein the loading dose is administered to the subject during and/or after the subject is exposed to the chemotherapy.

11. The method of claim 1 , further comprising administering to the subject the active agent at a maintenance dose in an amount that is about 25% to about 75% less than the amount of the active agent in the loading dose.

12. The method of claim 1 , wherein the amount of active agent administered to the subject in the loading dose is about 5 mg to about 50 mg.

13. The method of claim 1 , wherein the loading dose is only administered one time as the initial dose.

14. The method of claim 1 , further comprising administering to the subject a maintenance dose, wherein the amount of the active agent administered to the subject in the maintenance dose is about 5 mg/week to about 50 mg/week times the activity equivalent of BMX-001.

15. The method of claim 1 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered to the subject two or three times per week.

16. The method of claim 1 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered two or three times a week after an initial chemotherapy exposure.

17. The method of claim 1 , further comprising administering to the subject a maintenance dose, wherein the maintenance dose is administered every two or three days for 1 to 8 weeks after a final chemotherapy exposure.

18. The method of claim 1 , wherein the subject is further receiving radiation therapy.

19. The method of claim 18 , wherein the method treats and/or prevents radiation-induced normal tissue injury in the subject.

20. The method of claim 18 , wherein the method treats and/or prevents one or more side effects associated with the radiation therapy.

21. A method of treating and/or preventing one or more side effects associated with radiation and/or chemotherapy exposure in a subject during and/or following radiation and/or chemotherapy exposure, the method comprising:
administering to the subject prior to, during, or after radiation and/or chemotherapy exposure an active agent at a loading dose in an amount of about 0.05 mg/kg to about 1 mg/kg times the activity equivalent of BMX-001;
wherein the active agent is a meso-substituted metalloporphyrin, and
wherein the loading dose is only administered one time as an initial dose.

22. The method of claim 21 , wherein the active agent is a compound of Formula I:

wherein:
each R is independently selected from a substituted or unsubstituted aryl, heteroaryl, cycloalkyl, or heterocycloalkyl;
each A is an independently selected from a hydrogen, an electron-withdrawing group, or an electron donating group;
M is a metal; and
Z— is a counterion;
or a pharmaceutically acceptable salt thereof.

23. The method of claim 21 , wherein the active agent has a structure of Formula A1:

wherein:
each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;
each A is, independently, hydrogen or an electron withdrawing group;
M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and
Z— is a counterion;
or a pharmaceutically acceptable salt thereof.

24. The method of claim 21 , wherein the active agent has a structure of Formula B1:

wherein:
each R is independently C1-12 alkyl or C1-C12 alkoxyalkyl;
each A is, independently, hydrogen or an electron withdrawing group;
M is a metal selected from the group consisting of manganese, iron, copper, cobalt, and nickel; and
Z— is a counterion; or a pharmaceutically acceptable salt thereof.

25. The method of claim 21 , wherein the active agent has the structure:

Assignees

• Biomimetix Jv Llc
• Univ Duke

Inventors

• Ashcraft Kathleen
• Dewhirst Mark
• Batinic-Haberle Ines
• Crapo James D

Classifications

• A61P1/02

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• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P17/14

  for baldness or alopecia · CPC title

• A61K33/243

  Platinum; Compounds thereof · CPC title

• A61P17/00

  Drugs for dermatological disorders · CPC title