# US 8,784,899 B2 · Compositions and methods for cancer treatment

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- Number: US 8,784,899 B2
- Document ID: US8784899B2
- Status: Granted
- Kind: B2
- Application number: 11/542,645
- Filed: 2006-10-04
- Published: 2007-05-10
- Granted: 2014-07-22
- Earliest claimed: 2005-10-04
- Assignees: Samuel Waxman Cancer Research Foundation
- Applicants: Wilson H. Miller; Zuanel Diaz Heredia; Hyman M. Schipper; Koren K. Mann
- Inventors: Wilson H. Miller; Zuanel Diaz Heredia; Hyman M. Schipper; Koren K. Mann
- Web page: https://patentgrep.com/patent/US8784899B2

## CPC

- A61K 33/36: Arsenic; Compounds thereof
- A61K 31/355: Tocopherols, e.g. vitamin E
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention relates to compositions comprising a vitamin E analog and an arsenic compound for treating hyperproliferative cells disorders such as cancer. The composition of the invention potentiates arsenic toxicity towards cancer cells and can also prevent arsenic-mediated toxicity of non-cancerous cells.

## Claims

### Claim 1

A method for treating a mammal suffering from a neoplastic disease, the method comprising administering to said mammal a pharmaceutically effective amount of a composition comprising arsenic trioxide and 5 to 50 mg/kg body weight of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid wherein the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid enhances inhibition by the arsenic trioxide of hyperproliferation of the neoplastic cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein said mammal is a human.

### Claim 3 (depends on 1)

The method of claim 1, wherein said administering comprises intravenous, subcutaneous, intraperitoneal, intrathecal, intravesical, intradermal, intramuscular, or intralymphatic treatment.

### Claim 4 (depends on 1)

The method of claim 1, wherein the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid protects non-cancerous cells in the mammal from toxicity induced by the arsenic compound.

### Claim 5 (depends on 4)

The method of claim 4, wherein the non-cancerous cells are liver cells.

### Claim 6 (depends on 1)

The method of claim 1, wherein hyperproliferation of the neoplastic cells is inhibited.

### Claim 7 (depends on 1)

The method of claim 1, wherein apoptosis is induced in the neoplastic cells.

### Claim 8 (depends on 1)

The method of claim 1, wherein the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid and arsenic trioxide act synergistically to inhibit hyperproliferation of the neoplastic cells.

### Claim 9 (depends on 1)

The method of claim 1, wherein the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid and the arsenic trioxide act synergistically to induce apoptosis and/or to induce oxidative stress in the neoplastic cells.

### Claim 10 (depends on 1)

The method of claim 1, wherein the amount of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid is about 50 mg/kg body weight.

### Claim 11

A method for inducing apoptosis in neoplastic cells, said method comprising contacting said neoplastic cells with an effective amount of a composition comprising arsenic trioxide and 5 to 50 mg/kg body weight of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox™) that is non-toxic to neoplastic cells, wherein the Trolox™ enhances induction by the arsenic trioxide of the apoptosis.

### Claim 12 (depends on 11)

The method of claim 11, wherein hyperproliferation of the neoplastic cells is inhibited.

### Claim 13 (depends on 11)

The method of claim 11, wherein the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid and the arsenic trioxide act synergistically to induce the apoptosis.

### Claim 14 (depends on 12)

The method of claim 12, wherein the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid and the arsenic trioxide act synergistically to inhibit the hyperproliferation of the neoplastic cells.