USE OF A POLYPHENOL FOR THE TREATMENT OF A CANCEROUS OR PRECANCEROUS LESION OF THE SKIN

• US 20110166219A1
• Filed: 03/18/2011
• Published: 07/07/2011
• Est. Priority Date: 10/09/2003
• Status: Active Grant

• Current Assignee: Fougera Pharmaceuticals Incorporated (Novartis Ag)
• Original Assignee: Medigene AG
• Inventors: Stockfleth, Eggert
• Granted Patent: US 8,455,022 B2
• Time in Patent Office: Days
• US Class Current: 514/456
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 36/82 Theaceae (Tea family), e.g. camellia
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention refers to a method for treating cancerous or precancerous lesions of the skin by administering a pharmaceutically effective amount of a polyphenol to a patient as well as to the production of a medicament thereto.

Claims

1. A method for treating a cancerous lesion of the skin in a patient, said method comprising administering a pharmaceutically effective amount of a polyphenol to said patient.

2. The method according to claim 1, wherein the cancerous lesion is a pre-cancerous lesion.

3. The method according to claim 1, wherein the lesion of the skin is a non-virally induced lesion.

4. The method according to claim 3, wherein the lesion is a lesion not caused by papilloma virus.

5. The method according to claim 4, wherein the lesion is not a lesion selected from the group consisting of hyperplasia, Condyloma acuminata, warts and cervical intra-epithelial neoplasia.

6. The method according to claim 1, wherein the patient is a human.

7. The method according to claim 1, wherein the cancerous lesion of the skin is an advanced tumor.

8. The method according to claim 1, wherein the polyphenol is isolated from tea.

9. The method according to claim 1, wherein the polyphenol is extracted from a tea.

10. The method according to claim 9, wherein the tea is a green tea.

11. The method according to claim 1, wherein the polyphenol is isolated from a tea extract.

12. The method according to claim 1, wherein the polyphenol is selected from the group consisting of catechol, catechol gallate, epicatechol, epicatechol gallate, epigallocatechol, epigallocatechol gallate, gallocatechol and/or gallocatechol gallate.

13. The method according to claim 1, wherein the polyphenol has the general formula (I)

14. The method according to claim 12, wherein the catechol has the general formula (II)

15. The method according to claim 12, wherein the catechol is selected from the group consisting of (+)-catechol, (−

)-catechol, (+)-catechol gallate, (−

)-catechol gallate, (+)-epicatechol, (−

)-epicatechol, (+)-epicatechol gallate, (−

)-epicatechol gallate, (+)-epigallocatechol, (−

)-epigallocatechol, (+)-epigallocatechol gallate, (−

)-epigallocatechol gallate, (+)-gallocatechol, (−

)-gallocatechol, (+)-gallocatechol gallate and/or (−

)-gallocatechol gallate.

16. The method according to claim 1, wherein the polyphenol is present in the form of a mixture of polyphenols, in particular catechols, especially containing catechol, catechol gallate, epicatechol, epicatechol gallate, epigallocatechol, epigallocatechol gallate, gallocatechol and/or gallocatechol gallate, whereas the gallates of catechol, epicatechol, epigallocatechol or of gallocatechol are most preferred in the mixture of polyphenols.

17. The method according to claim 16, wherein the mixture of polyphenols is a tea extract.

18. The method according to claim 17, wherein the tea extract is a green tea extract.

19. The method according to claim 17, wherein the mixture of polyphenols is selected from the group consisting of catechol, catechol gallate, epicatechol, epicatechol gallate, epigallocatechol, epigallocatechol gallate, gallocatechol and/or gallocatechol gallate.

20. The method according to claim 19, wherein the catechols are selected from the group consisting of (−

)-epicatechol, (−

)-epicatechol gallate, (−

)-epigallocatechol, (−

)-epigallocatechol gallate, (+)-gallocatechol and/or (−

)-gallocatechol gallate.

21. The method according to claim 19, wherein the catechols are selected from the group consisting of about 2-20% (w/w) epicatechol, about 2-20% (w/w) epicatechol gallate, about 1-25% (w/w) epigallocatechol, about 40-75% (w/w) epigallocatechol gallate, about 0.05-5% (w/w) gallocatechol and/or about 0.5-20% (w/w) gallocatechol gallate.

22. The method according to claim 19, wherein the catechols are selected from the group consisting of about 10.8% (w/w) of epicatechol, about 6.5% (w/w) of epicatechol gallate, about 9.2% (w/w) of epigallocatechol, about 54.8% (w/w) of epigallocatechol gallate and/or about 4.0% (w/w) of gallocatechol gallate.

23. The method according to claim 19, wherein the mixture contains about 10.8% (w/w) of (−

)-epicatechol, about 6.5% (w/w) of (−

)-epicatechol gallate, about 9.2% (w/w) of (−

)-epigallocatechol, about 54.8% (w/w) of (−

)-epigallocatechol gallate and about 4.0% (w/w) of (−

)-gallocatechol gallate.

24. The method according to claim 19, wherein the catechols are selected from the group consisting of about 2-12% (w/w) epicatechol, about 4-15% (w/w) epicatechol gallate, about 1-8% (w/w) epigallocatechol, about 60-68% (w/w) epigallocatechol gallate, about 0.05-1% (w/w) gallocatechol and/or about 1-7% (w/w) gallocatechol gallate.

25. The method according to claim 19, wherein the catechols are selected from the group consisting of about 5-8% (w/w) epicatechol, about 5-7% (w/w) epicatechol gallate, about 2-3% (w/w) epigallocatechol, about 61-65% (w/w) epigallocatechol gallate and/or about 2-4% (w/w) of gallocatechol gallate.

26. The method according to claim 19, wherein the catechols are selected from the group consisting of about 5-8% (w/w) epicatechol, about 5-6% (w/w) epicatechol gallate, about 6-8% (w/w) epigallocatechol, about 61-65% (w/w) epigallocatechol gallate and/or about 2-4% (w/w) of gallocatechol gallate.

27. The method according to claim 1, wherein the polyphenol is combined with an additive.

28. The method according to claim 27, wherein the additive is selected from the group consisting of petroleum jelly, wax, oleyl alcohol, propylene glycol monostearate, propylene glycol monopalmitostearate and/or isopropyl myristate.

29. The method according to claim 1, wherein the polyphenol is administered topically.

30. The method according to claim 1, wherein the polyphenol is contained in a carrier selected from the group consisting of an emulsion, a gel, a cream and/or an ointment.

31. The method according to claim 1, wherein the method for treating said lesions is combined with a different anticancer treatment.

32. The method according to claim 31, wherein the different anticancer treatment is selected from the group consisting of surgery, electrodessication, curettage, excision, Mohs micrographic surgery, radiation, proton therapy, chemotherapy, photodynamic therapy, cryosurgery, laser, immunotherapy, vaccine therapy and/or biologic therapy.

33. The method according to claim 32, wherein the chemotherapy is carried out with an agent selected from the group consisting of podophyllin, 5-fluorouracil, bleomycin, interferon, imiquimod, and mixtures thereof.

34. The method according to claim 32, wherein the radiation is selected from the group consisting of X-ray radiation and γ

-radiation.

35. The method according to claim 1 or 2, wherein the lesion of the skin is selected from the group consisting of skin cancer, cutaneous carcinoma, basal cell carcinoma, squamous cell carcinoma, actinic keratosis, solar keratosis, epithelioma, epithelial tumors, skin neoplasm, Bowen'"'"'s disease, acanthoma, cancroid, cutaneous horn, hyperkeratosis, keratosis, molluscum contagiosum, lid tumors, xanthelasma, xanthoma, fibroma, verucca senilis, seborrheic keratosis, cheilocarcinoma, papillomatosis, penis carcinoma, radiodermatitis, sailor'"'"'s skin, tar cancer, vaginal carcinoma, vulvar cancer, erythroplasia queyrat and/or carcinoma of the tongue, in particular actinic or solar keratosis and/or basal cell carcinoma.