Compositions and methods for treatment of mammalian skin

• US 20110086088A1
• Filed: 03/19/2010
• Published: 04/14/2011
• Est. Priority Date: 10/14/2009
• Status: Active Grant

• Current Assignee: Berry Pharmaceuticals, LLC
• Original Assignee: Berry Pharmaceuticals, LLC
• Inventors: Berry, Don Wayne
• Granted Patent: US 8,652,534 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/438 The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• 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 36/74 Rubiaceae (Madder family)
• CPC Class Codes: A61K 8/46 containing sulfur A61K8/44 takes precedence
• CPC Class Codes: A61K 8/553 Phospholipids, e.g. lecithin
• CPC Class Codes: A61K 8/9789 Magnoliopsida [dicotyledons]
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• 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: A61Q 19/004 Aftersun preparations

Abstract

Compositions useful for treatment of a wide range of skin disorders including: pre-cancerous lesions, keratotic lesions, superficial basal cell carcinomae; squamous cell carcinomae; malignant melanoma, and radiation-induced burns. In some embodiments the treatments comprise contacting human or other mammalian skin with a composition according to the disclosure. In other embodiments, administration of compositions provided is by injection. Some embodiments provide for preventive use of compositions provided towards preventing some forms of skin cancer and skin cancer-related disorders by repeated application to healthy-looking skin. Methods for providing the compositions are disclosed.

Claims

1. A composition of matter useful for reducing symptoms of at least one disorder present on mammalian skin selected from the group consisting of:

pre-cancerous lesions, keratotic lesions, superficial basal cell carcinomae;

squamous cell carcinomae;

malignant melanoma, Merkel cell carcinomae, Kaposi'"'"'s sarcoma, cutaneous lymphomae and radiation-induced burns, said composition comprising an effective symptom-reducing amount of at least one material selected from the group consisting of;

alkaloids, 2-alpha-hydroxyursolic acid, apigenin-7-o-beta d-glucuronide, aricine, catequine, 19-alphahydroxy Asiatic acid, 24-methylenecycloartane-3β

-ol, 24-methylcycloart-24-en-3β

-ol, 2E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol, ephedrine, flavonones, 2′

-5-5′

-7-tetrahydroxy-7-o-rutinoside, isomaruquine, isopteropodine, maruquine, the methyl ester of maruquine, mitraphylline, narirutin, narirutin (2r), narirutin (2s), oxindole alkaloids, oxindole aricine, palmirine, pigenin-7-o-beta D-glucuronide, pomolic acid, pteropodine, rumberine, rosmarinic acid, rotundic acid, rumberine, rutin, seneciophylline, β

-sitosterol, speciophylline, stigmast-4-en-3-3-dione, stigmast-4-en-3-6-dione, stigmasterol, tannins, tormentic acid, uncarine F, and ursolic acid, and including any mixtures thereof.

2. A composition according to claim 1 comprising all of said materials recited in said group.

3. A composition according to claim 2 in which any one, or any combination including more than one, of said materials in said group are omitted from said composition.

4. A composition according to claim 1 wherein each material selected to be present in said composition is independently present in any amount between about 0.05% by weight and about 30% by weight based on the total weight of said composition, including all weight percentages and ranges of weight percentages therebetween.

5. A composition according to claim 3 wherein each material present in said composition is independently present in any amount between about 0.05% by weight and about 30% by weight based on the total weight of said composition, including all weight percentages and ranges of weight percentages therebetween.

6. A composition according to claim 1, wherein said composition is in any form selected from the group consisting of:

salves, creams, ointments, and lotions.

7. A composition according to claim 1, further comprising a pharmacologically-acceptable carrier, to provide a liquid suitable for injection into the dermis of a mammalian subject.

8. A composition according to claim 7 wherein said carrier comprises an emulsion.

9. A composition according to claim 1, further comprising an opthamologically-acceptable liquid carrier, to provide a composition suitable for administration to a mammalian eye.

10. A composition according to claim 1, further comprising a pharmacologically-acceptable carrier, to provide a liquid suitable for administration to nasal mucosa of a mammalian subject.

11. A composition according to claim 1 further comprising a carrier selected from the group consisting of:

water;

saline solution, any C1 to C4 alcohol;

any glyceryl ester oil; and

any mineral oil.

12. A composition according to claim 1 further comprising a nanoparticle.

13. A composition according to claim 12 wherein said nanoparticle is selected from the group consisting of:

solid core nanoparticles, hollow core nanoparticles, lipid nanoparticles, PEG nanoparticles, and chitosan nanoparticles, including any mixtures thereof.

14. A composition according to claim 1 further comprising a liposome.

15. Method for treating a disorder present in or on a mammalian subject, including tumors and disorders present on mammalian skin selected from the group consisting of:

pre-cancerous lesions, keratotic lesions, superficial basal cell carcinomae;

squamous cell carcinomae;

Kaposi'"'"'s sarcoma, cutaneous lymphomae, Merkel cell carcinomae, malignant melanomas, and radiation-induced burns, which method comprises contacting a composition containing a hamelia patens extract to said disorder in an effective amount and frequency for reducing symptoms of said disorder.

16. Method according to claim 15 wherein said extract comprises an effective symptom-reducing amount of at least one material selected from the group consisting of:

alkaloids, 2-alpha-hydroxyursolic acid, apigenin-7-o-beta d-glucuronide, aricine, catequine, 19-alphahydroxy Asiatic acid, 24-methylenecycloartane-3β

-ol, 24-methylcycloart-24-en-3β

-ol, 2E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol, ephedrine, flavonones, 2′

-5-5′

-7-tetrahydroxy-7-o-rutinoside, isomaruquine, isopteropodine, maruquine, the methyl ester of maruquine, mitraphylline, narirutin, narirutin (2r), narirutin (2s), oxindole alkaloids, oxindole aricine, palmirine, pigenin-7-o-beta D-glucuronide, pomolic acid, pteropodine, rumberine, rosmarinic acid, rotundic acid, rumberine, rutin, seneciophylline, β

-sitosterol, speciophylline, stigmast-4-en-3-3-dione, stigmast-4-en-3-6-dione, stigmasterol, tannins, tormentic acid, uncarine F, and ursolic acid, and including any mixtures thereof.

17. Method according to claim 16 wherein said composition comprises all of said materials recited in said group.

18. Method according to claim 17 wherein any one, or any combination including more than one, of said materials in said group are omitted from said composition.

19. Method according to claim 16 wherein each material selected to be present in said composition is independently present in any amount between about 0.05% by weight and about 30% by weight based on the total weight of said composition, including all weight percentages and ranges of weight percentages therebetween.

20. Method according to claim 18 wherein each material present in said composition is independently present in any amount between about 0.05% by weight and about 30% by weight based on the total weight of said composition, including all weight percentages and ranges of weight percentages therebetween.

21. Method according to claim 16, wherein said composition is in any form selected from the group consisting of:

salves, creams, ointments, and lotions.

22. Method according to claim 15, wherein said composition comprises a pharmacologically-acceptable carrier, to provide a liquid suitable for injection into the dermis of a mammalian subject.

23. Method according to claim 22 wherein said carrier comprises an emulsion.

24. Method according to claim 15, wherein said composition comprises an opthamologically-acceptable liquid carrier, to provide a composition suitable for administration to a mammalian eye.

25. Method according to claim 15, wherein said composition comprises a pharmacologically-acceptable carrier, to provide a liquid suitable for administration to nasal mucosa of a mammalian subject.

26. Method according to claim 15 wherein said composition comprises any carrier selected from the group consisting of:

water;

saline solution, any C1 to C4 alcohol;

any glyceryl ester oil; and

any mineral oil.

27. Method according to claim 15 wherein said composition comprises a nanoparticle.

28. Method according to claim 27 wherein said nanoparticle is selected from the group consisting of:

solid core nanoparticles, hollow core nanoparticles, lipid nanoparticles, PEG nanoparticles, and chitosan nanoparticles, including mixtures thereof.

29. Method according to claim 15 wherein said composition comprises a liposome.

30. Method according to claim 15 wherein said extract is an aqueous extract.

31. Method according to claim 15 wherein said extract is a non-aqueous extract.

32. Method according to claim 15 wherein said composition comprises a pharmaceutically-acceptable carrier.

33. Method according to claim 16 wherein said contacting comprises a method selected from the group consisting of:

injection of said composition into the basal layer of the dermis of a mammalian subject, and injection of said composition directly into the mass of a tumor.

34. Method for preventing the appearance of symptoms of a condition selected from the group consisting of:

pre-cancerous lesions, cancerous lesions, and keratotic lesions on the skin of a mammalian subject, comprising;

providing a composition comprising a hamelia patens extract; and

contacting mammalian skin with said composition on a repeat basis.

35. Method according to claim 34 wherein said composition comprises an effective symptom manifestation preventative amount of at least one material selected from the group consisting of alkaloids, 2-alpha-hydroxyursolic acid, apigenin-7-o-beta d-glucuronide, aricine, catequine, 19-alphahydroxy Asiatic acid, 24-methylenecycloartane-3β

-ol, 24-methylcycloart-24-en-3β

-ol, 2E-3,7,11,15,19-pentamethyl-2-eicosane-1-ol, ephedrine, flavonones, 2′

-5-5′

-7-tetrahydroxy-7-o-rutinoside, isomaruquine, isopteropodine, maruquine, the methyl ester of maruquine, mitraphylline, narirutin, narirutin (2r), narirutin (2s), oxindole alkaloids, oxindole aricine, palmirine, pigenin-7-o-beta D-glucuronide, pomolic acid, pteropodine, rumberine, rosmarinic acid, rotundic acid, rumberine, rutin, seneciophylline, β

-sitosterol, speciophylline, stigmast-4-en-3-3-dione, stigmast-4-en-3-6-dione, stigmasterol, tannins, tormentic acid, uncarine F, and ursolic acid, and including any mixtures thereof.

36. Method according to claim 35 wherein said composition comprises all of said materials recited in said group.

37. Method according to claim 36 wherein any one, or any combination including more than one, of said materials in said group are omitted from said composition.

38. Method according to claim 35 wherein each material selected to be present in said composition is independently present in any amount between about 0.05% by weight and about 30% by weight based on the total weight of said composition, including all weight percentages and ranges of weight percentages therebetween.

39. Method according to claim 37 wherein each material present in said composition is present in any amount between about 0.05% by weight and about 30% by weight based on the total weight of said composition, including all weight percentages and ranges of weight percentages therebetween.

40. Method according to claim 35, wherein said composition is in any form selected from the group consisting of:

salves, creams, ointments, and lotions.

41. Method according to claim 34, wherein said composition comprises a pharmacologically-acceptable carrier, to provide a liquid suitable for injection into the dermis of a mammalian subject.

42. Method according to claim 41 wherein said carrier comprises an emulsion.

43. Method according to claim 34, wherein said composition comprises an opthamologically-acceptable liquid carrier, to provide a composition suitable for administration to a mammalian eye.

44. Method according to claim 34, wherein said composition comprises a pharmacologically-acceptable carrier, to provide a liquid suitable for administration to nasal mucosa of a mammalian subject.

45. Method according to claim 34 wherein said composition comprises any carrier selected from the group consisting of:

water;

saline solution, any C1 to C4 alcohol;

any glyceryl ester oil; and

any mineral oil.

46. Method according to claim 34 wherein said composition comprises a nanoparticle.

47. Method according to claim 46 wherein said nanoparticle is selected from the group consisting of:

solid core nanoparticles, hollow core nanoparticles, lipid nanoparticles, PEG nanoparticles, and chitosan nanoparticles, including mixtures thereof.

48. Method according to claim 34 wherein said composition comprises a liposome.

49. Method according to claim 34 wherein said extract is an aqueous extract.

50. Method according to claim 34 wherein said extract is a non-aqueous extract.

51. Method according to claim 34 wherein said extract is a mixture comprising an aqueous hamelia patens extract and a non-aqueous hamelia patens extract.

52. Method according to claim 51 wherein said mixture is an emulsion.

53. Method according to claim 34 wherein said repeat basis comprises contacting said skin with said composition at least a once per month.

54. Method according to claim 34 wherein said repeat basis comprises contacting said skin with said composition at least a once per week.

55. Method according to claim 34 wherein said repeat basis comprises contacting said skin with said composition a plurality of times within in a single 24 hour period.