METHODS FOR PROTECTING THE SKIN FROM RADIATION INSULTS

• US 20110014137A1
• Filed: 04/16/2010
• Published: 01/20/2011
• Est. Priority Date: 10/16/2007
• Status: Abandoned Application

• Current Assignee: Johns Hopkins University
• Original Assignee: Johns Hopkins University
• Inventors: Talalay, Paul, Dinkova-Kostova, Albena T.
• Application Number:
  US12/761,551
• Publication Number:
  US 20110014137A1
• Time in Patent Office: Days
• US Class Current: 424/59
• CPC Class Codes: A61K 31/26 Cyanate or isocyanate esters; Thiocyanate or isothiocyanate esters
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/16 Emollients or protectives, e.g. against radiation
• CPC Class Codes: A61P 17/18 Antioxidants, e.g. antiradicals preparations for protection against sunlight A61Q17/00
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics

Abstract

The present invention relates to methods and compositions for the protection of skin and mucous membranes from undesirable side effects of ionizing radiation in a patient undergoing ionizing radiation therapy. In particular, the application describes compositions and methods comprising the topical use of Nrf2 inducers.

Claims

1. A method of protecting the skin and mucous membranes from an undesirable side effect of ionizing radiations in a patient undergoing ionizing radiation therapy comprising topically administering to the area of the patient'"'"'s body exposed to ionizing radiation and surrounding areas a composition comprising a therapeutically effective amount of an Nrf2 inducer.

2. The method of claim 1, wherein the undesirable side effect is selected from the group consisting of acute erythema, skin irritation, inflammation, edema, desquamation, necrosis of the skin, soreness, ulceration in the mouth, pain, fibrosis, telangiectasia, xerostomia, xerophthalmia, dryness of the vaginal mucosa, melanoma, breast cancer, stomach cancer, lung cancer and thyroid disorders.

3. The method of claim 1, wherein the Nrf2 inducer is a phase II enzyme inducer.

4. The method of claim 3, wherein the phase II inducer is an isothiocyanate.

5. The method of claim 4, wherein the phase II enzyme inducer is sulforaphane or a sulforaphane synthetic analogue.

6. The method of claim 5, wherein the sulforaphane synthetic analogue is selected from the group consisting of 6-isothiocyanato-2-hexanone, exo-2-acetyl-6-isothiocyanatonorbornane, exo-2-isothiocyanato-6-methylsulfonylnorbornane, 6-isothiocyanato-2-hexanol, 1-isothiocyanato-4-dimethylphosphonylbutane, exo-2-(1′

-hydroxyethyl)-5-isothiocyanatonorbornane, exo-2-acetyl-5-isothiocyanatonorbornane, 1-isothiocyanato-5-methylsulfonylpentane, cis-3-(methylsulfonyl)cyclohexylmethylisothiocyanate and trans-3-(methylsulfonyl)cyclohexylmethylisothiocyanate.

7. The method of claim 3, wherein the phase II inducer is a glucosinolate.

8. The method of claim 1, wherein the composition is administered to the patient prior to, during or after ionizing radiation therapy.

9. The method of claim 1, wherein the amount of Nrf2 inducer in the composition topically administered to the patient is from about 100 nmol to about 1 μ

mol/cm².

10. The method of claim 1, wherein the composition comprising the Nrf2 inducer is a topical preparation selected from the group consisting of ointment, cream, emulsion, lotion, gel and sunscreen.

11. The method of claim 1, wherein the patient is a mammal.

12. The method of claim 11, wherein the mammal is a human.

13. A composition for topical application to the skin comprising a therapeutically effective amount of an Nrf2 inducer and a vehicle selected from the group consisting of jojoba oil and evening primrose oil.

14. The composition of claim 13 in the form of ointment, cream, emulsion, lotion, gel or sunscreen.

15. The composition of claim 13, wherein the Nrf2 inducer is a phase II enzyme inducer.

16. The composition of claim 15, wherein the phase II inducer is an isothiocyanate.

17. The composition of claim 16, wherein the phase II enzyme inducer is sulforaphane or a sulforaphane synthetic analogue.

18. The composition of claim 17, wherein the sulforaphane synthetic analogue is selected from the group consisting of 6-isothiocyanato-2-hexanone, exo-2-acetyl-6-isothiocyanatonorbornane, exo-2-isothiocyanato-6-methylsulfonylnorbornane, 6-isothiocyanato-2-hexanol, 1-isothiocyanato-4-dimethylphosphonylbutane, exo-2-(1′

-hydroxyethyl)-5-isothiocyanatonorbornane, exo-2-acetyl-5-isothiocyanatonorbornane, 1-isothiocyanato-5-methylsulfonylpentane, cis-3-(methylsulfonyl)cyclohexylmethylisothiocyanate and trans-3-(methylsulfonyl)cyclohexylmethylisothiocyanate.

19. The composition of claim 15, wherein the Nrf2 inducer is a glucosinolate.

20. The composition of claim 13, wherein the amount of Nrf2 inducer is from about 100 nmol to about 1 μ

mol/cm².