Combination artemisinin and chemiluminescent photodynamic therapy and uses therefor

Patent metadata

Field	Value
Publication number	US-2016367674-A1
Application number	US-201615189655-A
Country	US
Kind code	A1
Filing date	Jun 22, 2016
Priority date	Jun 22, 2015
Publication date	Dec 22, 2016
Grant date	—

Abstract

Photodynamic therapy-based methods of treating diseases such as cancer and malaria are disclosed. These methods include administering 5-aminolevulinic acid (ALA), luminol and artemisinin (ART). ART and ALA administered in combination with luminol can kill malaria parasites without host toxicity. In some aspects, the methods further include administration of a luminol enhancer such as 4-iodophenol. The disclosed methods can also be used to remove potential malaria pathogens from the blood supply.

First claim

What is claimed is:

1 . A method of killing intraerythrocytic parasites, the method comprising contacting the parasites with therapeutically effective amounts of: 5-aminolevulinic acid or a derivative thereof; luminol or a derivative thereof; and artemisinin or a derivative thereof.

2 . The method of claim 1 , further comprising administering a therapeutically effective amount of 4-iodophenol.

3 . The method of claim 1 , wherein the artemisinin or derivative thereof is selected from the group consisting of artemisinin, artesunate, artemether, dihydroartesmisinin, artelinic acid, and artemotil.

4 . The method of claim 1 , wherein the artemisinin or derivative thereof is dihydroartesmisinin.

5 . The method of claim 1 , wherein the artemisinin or derivative thereof is administered at a sub-therapeutic dose.

6 . The method of claim 5 , wherein the sub-therapeutic dose is ≦10% of the EC 50 of the artemisinin or derivative thereof.

7 . The method of claim 1 , wherein the luminol or derivative thereof is selected from the group consisting of lumino, luminol sodium salt, luminol hemihydrate, luminol hydrochloride, isoluminol, isoluminol monohydrate, and isoluminol ABEI.

8 . The method of claim 1 , wherein the 5-aminolevulinic acid or derivative thereof is selected from the group consisting of 5-aminolevulinic acid (5-ALA), methylaminolevulinate, hexylaminolevulinate, 5-ALA esters, and 5-ALA amides.

9 . The method of claim 1 , wherein the killing of intraerythrocytic parasites is indicative by pyknosis.

10 . The method of claim 1 , wherein the parasites are drug-resistant.

11 . The method of claim 1 , wherein the parasites are artemisinin-resistant.

12 . A method of treating blood-stage malaria, the method comprising administering to a subject in need thereof, therapeutically effective amounts of: 5-aminolevulinic acid or a derivative thereof; luminol or a derivative thereof; and artemisinin or a derivative thereof.

13 . The method of claim 12 , further comprising administering a therapeutically effective amount of 4-iodophenol.

14 . The method of claim 12 , wherein the artemisinin or derivative thereof is selected from the group consisting of artemisinin, artesunate, artemether, dihydroartesmisinin, artelinic acid, and artemotil.

15 . The method of claim 12 , wherein the artemisinin or derivative thereof is dihydroartesmisinin.

16 . The method of claim 12 , wherein the artemisinin or derivative thereof is administered at a sub-therapeutic dose.

17 . The method of claim 16 , wherein the sub-therapeutic dose is ≦10% of the EC 50 of the artemisinin or derivative thereof.

18 . The method of claim 12 , wherein the luminol or derivative thereof is selected from the group consisting of lumino, luminol sodium salt, luminol hemihydrate, luminol hydrochloride, isoluminol, isoluminol monohydrate, and isoluminol ABEI.

19 . The method of claim 12 , wherein the 5-aminolevulinic acid or derivative thereof is selected from the group consisting of 5-aminolevulinic acid (5-ALA), methylaminolevulinate, hexylaminolevulinate, 5-ALA esters, and 5-ALA amides.

20 . The method of claim 12 , wherein the parasites are artemisinin-resistant.

Assignees

• Univ Washington

Inventors

• Goldberg Daniel E
• Sigala Paul

Classifications

• A61K31/357

  having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel · CPC title

• A61K41/0061 Primary

  5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA · CPC title

• A61K31/055

  the aromatic ring being substituted by halogen · CPC title

• A61K31/502

  ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine · CPC title

• A61K31/19

  Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60) · CPC title