Compositions and methods for protecting cells during cancer chemotherapy and radiotherapy

Patent metadata

Field	Value
Publication number	US-9839638-B2
Application number	US-201313742537-A
Country	US
Kind code	B2
Filing date	Jan 16, 2013
Priority date	May 5, 2000
Publication date	Dec 12, 2017
Grant date	Dec 12, 2017

Abstract

Compositions, pharmaceutical preparations and methods are disclosed for protecting non-neoplastic cells from damage caused by cancer chemotherapeutic agents or radiation therapy, during the course of cancer therapy or bone marrow transplant. These are based on the use of chemoprotective inducing agents that induce or increase production of cellular detoxification enzymes in target cell populations. The compositions and methods are useful to reduce or prevent hair loss, gastrointestinal distress and lesions of the skin and oral mucosa that commonly occur in patients undergoing cancer therapy. Also disclosed is a novel assay system for identifying new chemoprotective inducing agents.

First claim

We claim:

1. A method of protecting a non-neoplastic cell from toxic effects in a patient undergoing therapy comprising radiation therapy, the method comprising administering to the patient a pharmaceutical composition comprising 4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (“oltipraz”) in a delivery vehicle for delivering the oltipraz to the cell, wherein the administering comprises delivering the oltipraz to the cell in an amount sufficient to protect the cell from toxic effects of the radiation therapy on the cell, wherein the cell is an oral mucosal cell, and wherein the oltipraz is delivered to the oral mucosal cell through local administration of the composition and not systemic administration of the composition.

2. The method of claim 1 , wherein the therapy further comprises chemotherapy with one or more chemotherapeutic agents, and wherein the amount delivered to the oral mucosal cell is an amount sufficient to protect the oral mucosal cell from toxic effects of the radiation therapy and the one or more chemotherapeutic agents on the oral mucosal cell.

3. A method of protecting a non-neoplastic cell from toxic effects in a patient undergoing chemotherapy with one or more chemotherapeutic agents, the method comprising administering to the patient a pharmaceutical composition comprising 4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (“oltipraz”) in a delivery vehicle for delivering the oltipraz to the cell, wherein the administering comprises delivering the oltipraz to the cell in an amount sufficient to protect the cell from toxic effects of the one or more chemotherapeutic agents on the cell, wherein the cell is an oral mucosal cell, and wherein the oltipraz is delivered to the oral mucosal cell through local administration of the composition and not systemic administration of the composition.

4. The method of claim 3 , comprising delivering the oltipraz to the oral mucosal cell in an amount that induces or increases production of a phase I or phase II drug metabolizing enzyme in the cell.

5. A method of protecting a non-neoplastic oral mucosal cell from toxic effects in a patient undergoing therapy comprising radiation therapy, the method comprising administering to the patient a pharmaceutical composition comprising 4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (“oltipraz”) in a delivery vehicle for delivering the oltipraz to the oral mucosal cell, wherein the administering comprises delivering the oltipraz locally to the oral mucosal cell in an amount sufficient to protect the oral mucosal cell from toxic effects of the radiation therapy on the oral mucosal cell.

6. The method of claim 5 , wherein the therapy further comprises chemotherapy with one or more chemotherapeutic agents, and wherein the amount delivered to the oral mucosal cell is an amount sufficient to protect the oral mucosal cell from toxic effects of the radiation therapy and the one or more chemotherapeutic agents on the oral mucosal cell.

7. A method of protecting a non-neoplastic oral mucosal cell from toxic effects in a patient undergoing chemotherapy with one or more chemotherapeutic agents, the method comprising administering to the patient a pharmaceutical composition comprising 4-methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (“oltipraz”) in a delivery vehicle for delivering the oltipraz to the oral mucosal cell, wherein the administering comprises delivering the oltipraz locally to the oral mucosal cell in an amount sufficient to protect the oral mucosal cell from toxic effects of the one or more chemotherapeutic agents on the oral mucosal cell.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Fahl William E
• Raghavachari Nalini
• Zhu Ming
• Kink John A

Classifications

• A61K9/1272

  comprising non-phosphatidyl surfactants as bilayer-forming substances, e.g. cationic lipids or non-phosphatidyl liposomes coated or grafted with polymers (lipids as modifying agents {A61K47/543}) · CPC title

• A61K35/36

  Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39) · CPC title

• A61K9/127

  Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/497 Primary

  containing further heterocyclic rings · CPC title