Compositions and methods for topically treating diseases

• US 20050095283A1
• Filed: 09/14/2004
• Published: 05/05/2005
• Est. Priority Date: 09/16/2003
• Status: Abandoned Application

• Current Assignee: Aphios Corporation
• Original Assignee: Aphios Corporation
• Inventors: Weiner, Norman D., Castor, Trevor P.
• Application Number:
  US10/940,370
• Publication Number:
  US 20050095283A1
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911

Abstract

Described herein are compositions and methods for treating disease. In one aspect, the compositions comprise an anti-neoplastic agent together with a liposome preparation. In another aspect, the compositions of the present invention are directed toward the treatment of cancer. In a particular aspect, the cancer target is Kaposi'"'"'s sarcoma. The compositions described herein can be topically applied to a subject'"'"'s integumentary system using liposomal technology.

Claims

1. A method of treating disease, comprising topical administration to a subject in need thereof a therapeutically effective amount of a pharmaceutical agent formulated in a liposomal preparation.

2. The method of claim 1, wherein said disease is a cancer.

3. The method of claim 2, wherein said cancer is Kaposi'"'"'s sarcoma.

4. The method of claim 1, wherein said pharmaceutical agent is selected from the group consisting of paclitaxel, 5-FU, 5-FUdR, methotrexate, ara-C, 6-mercaptopurine, 6-thioguanine, hydroxyurea, mechlorethamine, phenylalanine mustard, chlorambucil, ethylenimines, methyl melamines, carmustine, lomustine, streptozocin, Cisplatin, Carboplatin, dacarbazine, procarbazine, doxorubicin, daunorubicin, mitomycin C, plycamycin, cyclophosphamide, melphalan, chlorambucil, carmustine, thiotepa, busulfan, prednisone, prednisolone, triamcinolone, and derivatives thereof.

5. The method of claim 4, wherein said pharmaceutical agent is paclitaxel and derivatives thereof.

6. The method of claim 5, wherein said derivatives are selected from the group consisting of 7-deoxy-docetaxol, 7,8-cyclopropataxanes, N-substituted 2-azetidones, 6,7-epoxy paclitaxels, 6,7-modified paclitaxels, 10-desacetoxytaxol, 10-deacetyltaxol, phosphonooxy and carbonate derivatives of taxol, taxol 2′

,7-di(sodium 1,2-benzene-dicarboxylate, 10-desacetoxy-11,12-dihydrotaxol-10,12(18)-diene derivatives, 10-desacetoxytaxol, Protaxol (2′

-and/or 7-O-ester derivatives ), (2′

-and/or 7-O-carbonate derivatives), asymmetric synthesis of taxol side chain, fluoro taxols, 9-deoxotaxane, (13-acetyl-9-deoxobaccatine III, 9-deoxotaxol, 7-deoxy-9-deoxotal, 10-desacetoxy-7-deoxy-9-deoxotaxol, derivatives containing hydrogen or acetyl group and a hydroxy and tert-butoxycarbonylamino, sulfonated 2′

-acryloyltaxol and sulfonated 2′

-O-acyl acid taxol derivatives, succinyltaxol, 2′

-γ

-aminobutyryltaxol formate, 2′

-acetyl taxol, 7-acetyl taxol, 7-glycine carbamate taxol, 2′

-OH-7-PEG(5000) carbamate taxol, 2′

-benzoyl and 2′

,7-dibenzoyl taxol derivatives, other prodrugs (2′

-acetyltaxol;

2′

,7-diacetyltaxol;

2′

succinyltaxol;

2′

-(beta-alanyl)-taxol), 2′

γ

-amino-butyryltaxol formate, ethylene glycol derivatives of 2′

-succinyltaxol, 2′

-glutaryltaxol, 2′

-(N,N-dimethylglycyl) taxol, 2′

-(2-(N,N-dimethylamino)propionyl)taxol, 2′

orthocarboxy-benzoyl taxol;

2′

aliphatic carboxylic acid derivatives of taxol, Prodrugs {2′

(N,N-diethylamino-propionyl)taxol, 2′

(N,N-dimethyglycyl)taxol, 7(N,N-dimethyl-glycyl)taxol, 2′

,7-di-(N,N-dimethylglycyl)taxol, 7(N,N-diethylaminopropionyl)taxol, 2′

,7-di(N,N-diethyl-aminopropionyl)taxol, 2′

-(L-glycyl)taxol, 7-(L-glycyl)taxol, 2′

,7-di(L-glycyl)taxol, 2′

-(L-alanyl)taxol, 7-(L-alanyl)taxol, 2′

,7-di(L-alanyl)taxol, 2′

-(L-leucyl)taxol, 7-(L-leucyl) taxol, 2′

,7-di(L-leucyl)taxol, 2′

-(L-isoleucyl)taxol, 7-(L-isoleucyl)taxol, 2′

,7-di(L-iso-leucyl)taxol, 2′

-(L-valyl)taxol, 7-(L-valyl)taxol, 2′

7-di(L-valyl)taxol, 2′

-(L-phenylalanyl) taxol, 7-(L-phenylalany)taxol, 2′

,7-di(L-phenylalanyl)taxol, 2′

-(L-prolyl)taxol, 7-(L-prolyl)taxol, 2′

,7-di(L-prolyl)taxol, 2′

-(L-lysyl)taxol, 7-(L-lysyl)taxol, 2′

,7-di(L-lysyl)taxol, 2′

-(L-glutamyl) taxol, 7-(L-glutamyl)taxol, 2′

,7-di(L-glutamyl)taxol, 2′

-(L-arginyl)taxol, 7-(L-arginyl)taxol, 2′

,7-di(L-arginyl)taxol}, Taxol analogs with modified phenylisoserine side chains, taxotere, (N-debenzoyl-N-tert-(butoxycaronyl)-10-de-acetyltaxol, and taxanes.

7. The method of claim 1, wherein said liposomal preparation comprises a lipid bilayer.

8. The method of claim 1, wherein said liposomal preparation encapsulates said pharmaceutical agent.

9. The method of claim 8, wherein said encapsulation is within an aqueous layer of said liposomal preparation.

10. The method of claim 1, wherein said liposomal preparation is selected from the group consisting of an ULV, MLV and OLV.

11. The method of claim 10, wherein said liposomal preparation is an ULV.

12. The method of claim 10, wherein said liposomal preparation is an MLV.

13. The method of claim 10, wherein said liposomal preparation is OLV.

14. The method of claim 1, wherein said liposomal preparation is multivesicular.

15. The method of claim 1 further comprising one or more excipients.

16. The method of claim 15, wherein said excipients are selected from the group consisting of alcohols, glycols, isopropyl myristate, water, mixtures thereof, eineol, D-limonene (with or without water), ethylene glycol or propylene glycol, phosphatidyl glycerol, dioleoylphosphatidyl glycerol, Transcutolo, or terpinolene;

mixtures of isopropyl myristate and 1-hexyl-2-pyrrolidone, N-dodecyl-2-piperidinone or 1-hexyl-2-pyrrolidone, and sodium lauryl sulfate.

17. The method of claim 1, wherein said liposomal preparation is a nonionic nansomal formulation.

18. A method of treating cancer, comprising topical administration to a subject in need thereof a therapeutically effective amount of a pharmaceutical agent formulation in a liposomal preparation.