Claims for Patent: 5,008,294

Summary for Patent: 5,008,294

Title:	Methods of treating tumors with compositions of catecholic butanes
Abstract:	The invention relates to methods useful in the treatment of benign, premalignant and malignant solid tumors, especially those of the skin comprising methods for the administration of pharmacologically active compositions containing catecholic butanes. The invention also relates to methods of preventing the occurence of tumors, and the use of catecholic butanes as a sunscreening agent. The preferred catecholic butane is nordihydroguaiaretic acid. The preferred methods of application of the compositions containing catecholic butanes are by topical application and intratumor injection.
Inventor(s):	Neiss; Edward S. (Denver, CO), Allen; Larry M. (Golden, CO)
Assignee:	Chemex Pharmaceuticals, Inc. (Denver, CO)
Application Number:	07/057,481
Patent Claims:	1. A method for inhibiting the growth of a tumor which comprises topically administering to the situs of the tumor of a mammal in need of said treatment an effective amount of a composition comprising at least 1 catecholic butane of the formula: ##STR3## wherein R.sub.1 and R.sub.2 are independently H, lower alkyl, lower acyl, or alkylene; R.sub.3, and R.sub.4, R.sub.5, R.sub.6, R.sub.10, R.sub.11, R.sub.12 and R.sub.13 are independently H or lower alkyl; R.sub.7, R.sub.8 and R.sub.9 are independently H, hydroxy, lower alkoxy, lower acyloxy, or any two adjacent groups together may be alkylene dioxy. 2. The method according to claim 1 wherein the composition contains 0.1-10 wt. % of said catecholic butane. 3. The method according to claim 1 wherein the catecholic butane is nordihydroguaiaretic acid. 4. The method according to claim 1 wherein said catecholic butane contains at least one lower alkyl ether derivative moiety. 5. The method according to claim 1 wherein said catecholic butane contains at least one lower acyl esther derivative moiety. 6. The method according to claim 1, wherein lower alkyl is C.sub.1 -C.sub.6 alkyl, R.sub.3 and R.sub.4 are C.sub.1 -C.sub.3 alkyl and the lower acyl is a C.sub.1 -C.sub.6 acyl. 7. The method according to claim 1, wherein the catecholic butane is selected from the group consisting of 1,4-bis(3,4-dihydroxphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dihydroxyphenyl)butane; 1,4-bis(3,4-dimethoxyphenyl)-2,3 -dimethylbutane; 1,4-bis(3,4-diethoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipropoxyphenyl)-2,3-dimethylbutane; 1-(3,4-dihydroxyphenyl)-4-(3,4,5-trihydroxyphenyl) butane; 1,4-bis(3,4-diacetoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipropionyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dibutyroyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-divaleroyloxphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipivaloyloxphenyl)-2,3-dimethylbutane; 1,4-bis (3,4-dipivaloyloxyphenyl) butane; 1,4-bis(3,4-dineopentylcarboxylphenyl)-2,3-dimethylbutane; and 1-(3,4-dihydroxyphenyl)-4-phenylbutane; 1-(3,4-dihydroxyphenyl)-4-(2,5 dihydroxyphenyl) butane. 8. The method according to claim 1 wherein the composition includes a pharmaceutically acceptable carrier. 9. The method according to claim 1 wherein said administering is effectuated by means selected from the group consisting of administration to the surface of the skin at the situs of the tumor and injection of the composition into the interior or near vicinity of the tumor. 10. The method according to claim 1 wherein the tumor are selected from the group consisting of equine sarcoid, equine papilloma, equine malignant melanoma, equine squamous cell carcinoma, canine perianal adenoma, canine mast cell carcinoma, canine breast adenocarcinoma and canine malignant melanoma. 11. The method according to claim 10, wherein the catecholic butane is nordihydroguaiaretic acid. 12. The method according to claim 11, wherein 10 nanomoles of composition are applied to each milliliter of solid tumor. 13. The method according to claim 10 wherein said administering is effectuated by means selected from the group consisting of topical administration to the surface of the skin at the situs of the tumor and injection of the composition into the interior or near vicinity of the tumor. 14. The method according to claim 10 wherein said catecholic butane is substantially nordihydroguaiaretic acid. 15. The method according to claim 1 wherein the tumor is selected from the group consisting of malignant melanoma, mammary tumor, basal cell carcinoma, squamous cell carcinoma, and epidermal tumors of the skin. 16. A method for treating tumors of the skin, which comprises administering to the skin of a mammal in need of said treatment an effective amount of a composition comprising at least one catecholic butane of the formula: ##STR4## wherein R.sub.1 and R.sub.2 are independently H, lower alkyl, lower acyl or alkylene; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.10, R.sub.11, R.sub.12 and R.sub.13 are independently H or lower alkyl; R.sub.7, R.sub.8 and R.sub.9 are independently H, hydroxy, lower alkoxy, lower acyloxy, or any two adjacent groups may be alkylene dioxy. 17. The method according to claim 16 wherein the composition includes a pharmaceutically acceptable carrier. 18. The method for treating a keratosis of the skin which comprises administering to the skin of a mammal in need of said treatment at the situs of the keratosis an effective amount of a composition comprising at least one catecholic butane of the formula: ##STR5## wherein R.sub.1 and R.sub.2 are independently H, lower alkyl or lower acyl; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.10, R.sub.11, R.sub.12 and R.sub.13 are independently H or lower alkyl; and R.sub.7, R.sub.8 and R.sub.9 are independently H, hydroxy, lower alkoxy or lower acyloxy. 19. The method according to claim 18 wherein the catecholic butane is selected from the group consisting of nordihydroguaiaretic acid in any of its racemic forms, nordihydroguaiaretic acid tetrapivalate, nordihydroguaiaretic acid tetrapropionate and all optical configurations thereof. 20. The method according to claim 19 wherein the catecholic butane is nordihydroguaiaretic acid. 21. The method according to claim 18 wherein the composition contains 0.1-10 wt. % of said catecholic butane. 22. The method according to claim 18 wherein said catecholic butane contains at least one lower alkyl ether derivative moiety. 23. The method according to claim 18 wherein said catecholic butane contains at least one lower acyl ester derivative moiety. 24. The method according to claim 18, wherein lower alkyl is C.sub.1 -C.sub.6 alkyl, R.sub.3 and R.sub.4 are C.sub.1 -C.sub.3 alkyl and the lower acyl is a C.sub.1 -C.sub.6 acyl. 25. The method according to claim 18, wherein the catecholic butane is selected from the group consisting of 1,4-bis(3,4-dihydroxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dihydroxyphenyl)butane; 1,4-bis(3,4-dimethoxyphenyl)-2,3 -dimethylbutane; 1,4-bis(3,4-diethoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipropoxyphenyl)-2,3-dimethylbutane; 1-(3,4-dihydroxyphenyl)-4-(3,4,5-trihydroxyphenyl) butane; 1,4-bis(3,4-diacetoxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipropionyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dibutyroyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-divaleroyloxyphenyl)-2,3-dimethylbutane; 1,4-bis(3,4-dipivaloyloxphenyl)-2,3-dimethylbutane; 1,4-bis (3,4-dipivaloyloxyphenyl) butane; 1,4-bis(3,4-dineopentylcarboxylphenyl)-2,3-dimethylbutane; and 1-(3,4-dihydroxyphenyl)-4-phenylbutane; 1-(3,4-dihydroxyphenyl)-4-(2,5 dihydroxyphenyl) butane. 26. The method according to claim 18 wherein the composition includes a pharmaceutically acceptable carrier. 27. The method according to claim 18 wherein the keratosis is actinic keratosis. 28. A method for treating actinic keratosis which comprises administering to the skin of a mammal in need of said treatment at the situs of the actinic keratosis an effective amount of a composition comprising at least one catecholic butane of the formula: ##STR6## wherein R.sub.1 and R.sub.2 are independently H, lower alkyl, or lower acyl and R.sub.1 and R.sub.2 together may be alkylene; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.10, R.sub.11, R.sub.12 and R.sub.13 are independently H or lower alkyl; and R.sub.7, R.sub.8 and R.sub.9 are independently H, hydroxy, lower alkoxy, lower acyloxy, or any two adjacent groups may be aklylene dioxy. 29. The method according got claim 28 wherein the catecholic butane is selected from the group consisting of nordihydroguaiaretic acid in any of its racemic forms, nordihydroguaiaretic acid tetrapivalate, nordihydroguaiaretic acid tetrapropionate and all optical configurations thereof. 30. A method for treating actinic keratosis which comprises administering to the skin of a mammal in need of said treatment at the situs of the actinic keratosis an effective amount of a composition comprising nordihydroguaiaretic acid. 31. A method for treating tumors of the skin which comprises administering to the skin of a mammal in need of said treatment an effective amount of a composition comprising at least one catecholic butane of the formula: ##STR7## wherein R.sub.1 is H, lower alkyl or lower acyl, R.sub.2 is lower acyl and R.sub.1 and R.sub.2 together may be alkylene; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.10, R.sub.11, R.sub.12 R.sub.13 are independently H or lower alkyl; and R.sub.7, R.sub.8 and R.sub.9 are independently H, hydroxy, lower alkoxy or lower acyloxy; or any two adjacent groups together may be alkylene dioxy. 32. A method for treating tumors of the skin which comprises administering to the skin of a mammal in need of said treatment an effective amount of a composition comprising at least one catecholic butane of the formula: ##STR8## wherein R.sub.1 and R.sub.2 are independently H, lower alkyl or lower acyl and R.sub.1 and R.sub.2 together may be alkylene; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.10, R.sub.11, R.sub.12 and R.sub.13 are H; and R.sub.7, R.sub.8 and R.sub.9 are independently H, hydroxy, lower alkoxy or lower acyloxy; or any two adjacent groups together may be alkylene dioxy. 33. A method for treating tumors of the skin which comprises administering to the skin of a mammal in need of said treatment an effective amount of a composition comprising at least one catecholic butane of the formula: ##STR9## wherein R.sub.1, R.sub.2, R.sub.7 and R.sub.8 are lower acyl; R.sub.3 and R.sub.4 are methyl; and R.sub.5, R.sub.6, R.sub.9, R.sub.10, R.sub.11, R.sub.12 and R.sub.13 are H. 34. The method for treating tumors of the skin according to claim 33 wherein the tumor is actinic keratosis.