Methods of treating chronic and neuropathic pain mediated by N-type neuronal calcium channels using D-enantiomeric peptides

Patent metadata

Field	Value
Publication number	US-11224632-B2
Application number	US-201716470616-A
Country	US
Kind code	B2
Filing date	Dec 21, 2017
Priority date	Dec 23, 2016
Publication date	Jan 18, 2022
Grant date	Jan 18, 2022

Abstract

The present invention relates to a composition consisting of or containing peptides selected from the group consisting of or containing RD2, D3, homologs having at least 50% identity and derivatives of RD2 or D3 and also polymers containing or consisting of RD2/D3 homologs having at least 50% identity and derivatives of RD2 and under D3 for use as an analgesic, for use in pain therapy, for use in the treatment of chronic and/or neuropathic pain and/or for inhibiting N-type neuronal calcium channels (NCCs).

First claim

What is claimed is:

1. A method of treating pain mediated by N-type neuronal calcium channels (NCCs), wherein the method comprises administering to a subject in need thereof a therapeutically effective amount of a composition consisting of or comprising one or both of peptides “RD2” (SEQ ID NO: 1) and “D3” (SEQ ID NO: 2) and/or a polymer comprising one or both of RD2 (SEQ ID NO: 1) and D3 (SEQ ID NO: 2), thereby reducing the pain mediated by NCCs in the subject when compared to no treatment with the composition.

2. The method of claim 1 , wherein chronic pain is treated.

3. The method of claim 1 , wherein neuropathic pain is treated.

4. The method of claim 1 , wherein NCCs the N-type neuronal calcium channels (NCCs) are blocked.

5. The method of claim 1 , wherein the peptides are composed essentially of D-enantiomers.

6. The method of claim 1 , wherein the composition comprises RD2 (SEQ ID NO: 1) and/or a polymer comprising RD2 (SEQ ID NO: 1).

7. The method of claim 1 , wherein the composition comprises D3 (SEQ ID NO: 2) and/or a polymer comprising D3 (SEQ ID NO: 2).

8. The method of claim 1 , wherein the peptides are administered in a dose of from 1 μg to 1 g per kilo of body weight.

9. The method of claim 1 , wherein the composition is administered by one or more of intravenous, subcutaneous, intraperitoneal, intranasal or oral administration.

10. The method of claim 1 , wherein the composition is administered orally.

11. The method of claim 4 , wherein the composition has an IC 50 value of 1 nanomolar to 1 millimolar for N-type NCCs.

12. A method of reducing the release of neurotransmitters associated with pain and mediated by N-type neuronal calcium channels (NCCs) in a subject in need thereof, wherein the method comprises contacting the NCCs in the subject with a composition consisting of or comprising one or both of peptides RD2 (SEQ ID NO: 1) and D3 (SEQ ID NO: 2) and/or a polymer comprising one or both of RD2 (SEQ ID NO: 1) and D3 (SEQ ID NO: 2) for use as an analgesic in the subject in need thereof, thereby reducing the release of neurotransmitters associated with pain and mediated by NCCs in the subject when compared to no treatment with the composition.

13. The method of claim 12 , wherein a calcium influx through the NCC in the subject is reduced compared to a control subject with no treatment with the composition.

14. The method of claim 13 , wherein the function of L-type NCCs in the subject is not modified when compared to a control subject with no treatment with the composition.

15. A method of inhibiting an N-type NCC in a subject in need thereof, wherein the method comprises contacting the N-type NCC in the subject in need thereof with a composition consisting of or comprising one or both of peptides RD2 (SEQ ID NO: 1) and D3 (SEQ ID NO: 2) and/or a polymer comprising one or both of RD2 (SEQ ID NO: 1) and D3 (SEQ ID NO: 2), thereby inhibiting the N-type NCC in the subject when compared to no treatment with the composition.

16. The method of claim 15 , wherein the function of L-type NCCs in the subject is not modified when compared to a control subject with no treatment with the composition.

Assignees

• Forschungszentrum Juelich Gmbh

Inventors

• Willbold Dieter
• Juergens Dagmar
• Kutzsche Janine
• Castro Gustavo Adolfo Guzman
• Jimenez Patricia Hidalgo

Classifications

• A61K38/10 Primary

  Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07K11/00

  Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title