Modified tetracycline for treatment of alcohol use disorder, pain and other disorders involving potential inflammatory processes

Patent metadata

Field	Value
Publication number	US-11542227-B2
Application number	US-201916973896-A
Country	US
Kind code	B2
Filing date	Jun 13, 2019
Priority date	Jun 13, 2018
Publication date	Jan 3, 2023
Grant date	Jan 3, 2023

Abstract

A method of treating Alcohol Use Disorder (AUD), Substance Use Disorder (SUD), tobacco use, pain, or proinflammatory disorders comprising: providing a subject with an effective amount of a modified tetracycline or derivative thereof to ameliorate or eliminate the AUD, SUD, tobacco use, pain, or proinflammatory disorder, and wherein the modified tetracycline or derivative thereof has reduced binding to a microbial ribosome and has the formula wherein R1 is acetyl, R2 is OH or acetyl, R3 is acetyl, R4 is H or acetyl, and R5 is acetyl.

First claim

What is claimed is:

1. A method of treating a Substance Use Disorder (SUD), comprising:
providing a subject with an effective amount of a modified tetracycline or derivative thereof to ameliorate the SUD, and wherein the modified tetracycline or derivative thereof has reduced binding to a microbial ribosome and has the formula:

R 1 is methyl, ethyl, propyl, butyl, acetyl, alkyl, R 2 is H, OH or acetyl, R 3 is H or acetyl, R 4 is H or acetyl, and R 5 is H or acetyl.

2. The method of claim 1 , wherein the modified tetracycline has the formula:

3. The method of claim 1 , wherein the modified tetracycline has at least one of: moderate to no antibacterial activity, or has moderate to no antifungal activity.

4. The method of claim 1 , wherein the ribosome is a bacterial ribosome.

5. The method of claim 1 , wherein the modification at least one of: produces steric hindrance, blocks hydrogen bonding, or change coordination with divalent cations.

6. The method of claim 1 , wherein the modified tetracycline further comprises a pharmaceutically acceptable buffer, excipient, filler, or carrier.

7. The method of claim 1 , wherein the modified tetracycline is adapted for administration orally, enterally, parenterally, intramuscularly, intravenously, or intraperitoneally.

8. A method of evaluating a candidate drug believed to be useful in treating Substance Use Disorder (SUD), the method comprising:
a) measuring the SUD from a set of patients;
b) administering a candidate drug to a first subset of the patients, and a placebo to a second subset of the patients, wherein the candidate drug is a C6′ modified tetracycline that has the formula:

R 1 is methyl, ethyl, propyl, butyl, acetyl, alkyl, R 2 is H, OH or acetyl, R 3 is H or acetyl, R 4 is H or acetyl, and R 5 is H or acetyl;
c) repeating step a) after the administration of the candidate drug or the placebo; and
d) determining if the candidate drug reduces the SUD that is statistically significant as compared to any reduction occurring in the second subset of patients, wherein a statistically significant reduction indicates that the candidate drug is useful in treating SUD.

9. The method of claim 8 , wherein the modified tetracycline has the formula:

10. The method of claim 8 , wherein the modification at least one of: produces steric hindrance, blocks hydrogen bonding, or change coordination with divalent cations.

11. A method of treating a Substance Use Disorder (SUD) comprising:
identifying a subject in need of treatment for SUD; and
providing the subject with an effective amount of a modified tetracycline or derivative thereof to ameliorate the SUD, and wherein the modified tetracycline or derivative thereof has reduced binding to a microbial ribosome and has the formula:

R 1 is methyl, ethyl, propyl, butyl, acetyl, alkyl, R 2 is H, OH or acetyl, R 3 is H or acetyl, R 4 is H or acetyl, and R 5 is H or acetyl, in a pharmaceutically acceptable carrier.

12. The method of claim 11 , wherein the modified tetracycline has the formula:

13. The method of claim 11 , wherein the modified tetracycline has at least one of: moderate to no antibacterial activity, or has moderate to no antifungal activity.

14. The method of claim 11 , wherein the ribosome is a bacterial ribosome.

15. The method of claim 11 , wherein the modification at least one of: produces steric hindrance, blocks hydrogen bonding, or change coordination with divalent cations.

16. The method of claim 11 , wherein the modified tetracycline further comprises a pharmaceutically acceptable buffer, excipient, filler, or carrier.

17. The method of claim 11 , wherein the modified tetracycline is adapted for administration orally, enterally, intramuscularly, parenterally, intravenously, or intraperitoneally.

Assignees

• Univ Texas Tech System

Inventors

• Bergeson Susan E
• Syapin Peter
• Reid Ted W
• Shashtri Mayank
• Tran Phat

Classifications

• A61P25/32

  Alcohol-abuse · CPC title

• C07C2603/46

  1,4,4a,5,5a,6,11,12a- Octahydronaphthacenes, e.g. tetracyclines · CPC title

• A61P25/30 Primary

  for treating abuse or dependence · CPC title

• A61K31/65

  Tetracyclines · CPC title

• C07C237/26 Primary

  of a ring being part of a condensed ring system formed by at least four rings, e.g. tetracycline · CPC title