Claims for Patent: 8,178,123

Summary for Patent: 8,178,123

Title:	Method for augmentation of intraepithelial and systemic exposure of therapeutic agents having substrate activity for cytochrome P450 enzymes and membrane efflux systems following vaginal and oral cavity administration
Abstract:	A vaginal or buccal delivery of therapeutic agents having a substrate affinity for metabolic cytochrome P-450 enzymes and membrane efflux transporter systems. A method for augmentation of systemic exposure to the therapeutic agents having a substrate affinity for cytochrome P-450 enzymes and membrane efflux transporter systems, by delivering said agents to the systemic circulation through vaginal or buccal mucosa.
Inventor(s):	Pauletti; Giovanni M. (Loveland, OH), Harrison; Donald C. (Cincinnati, OH), Desai; Kishorkumar J. (Westchester, OH)
Assignee:	Femina Pharma Incorporated (Miami, FL)
Application Number:	11/522,126
Patent Claims:	1. An anti-viral or anti-cancer composition suitable for treatment of cancer and HIV/AIDS by providing a subject in need thereof with a mucosal composition administered vaginally or through an oral cavity, said composition comprising at least one anti-viral or one anti-cancer agent in an amount sufficient to provide a therapeutic effect in combination with 0.01 to 50% by weight of a non-ionizable glycol ether or with 0.001-10% by weight of a botanical bioavailability modulator, or a combination of both. 2. The composition of claim 1 wherein said anti-viral drug is an attachment inhibitor, fusion inhibitor, antiretroviral drug, nucleoside or nucleotide reverse transcriptase inhibitor or anti-HIV protease inhibitor. 3. The composition of claim 1 wherein said anti-cancer drug is an alkylating agent, antimetabolite, DNA cutter or DNA binder, topoisomerase I or topoisomerase II poison, or taxol or taxol derivative. 4. The composition of claim 1 wherein said non-ionizable glycol ether is selected from the group consisting of ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, triethylene glycol monomethyl ether, polyethylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monoethyl ether, triethylene glycol monoethyl ether, ethylene glycol monoisopropyl ether, ethylene glycol monobutyl ether, diethylene glycol monobutyl ether, triethylene glycol monobutyl ether, ethylene glycol monoisobutyl ether, diethylene glycol monohexyl ether, ethylene glycol mono 2-ethylhexyl ether, diethylene glycol mono 2-ethylhexyl ether, ethylene glycol monoallyl ether, ethylene glycol monophenyl ether, ethylene glycol monobenzyl ether, diethylene glycol monobenzyl ether, propylene glycol monomethyl ether, dipropylene glycol monomethyl ether, tripropylene glycol monomethyl ether, dipropylene glycol monopropyl ether, propylene glycol monobutyl ether, dipropylene glycol monobutyl ether, propylene glycol monophenyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, diethylene glycol diethyl ether, diethylene glycol dibutyl ether, dipropylene glycol dimethyl ether, diethylene glycol monoethyl ether and ethoxydiglycol. 5. The composition of claim 1 wherein said botanical bioavailability modulator is selected from the group consisting of Actaea racemosa L. (Ranunculaceae), Aesculus hippocastanum L. (Hippocastanaceae), Allium ampeloprasum L. (Liliaceae), Allium sativum L. (Liliaceae), Allium tuberosum Rottl. (Liliaceae), Alpinia galangal L. (Zingiberaceae), Boswellia carteri Birdw. (Burseraceae), Boswellia frereana Birdw. (Burseraceae), Boswellia sacra Flueckiger (Burseraceae), Boswellia serrata Roxb. (Burseraceae), Camelia sinensis Kuntze (Theaceae), Catharanthus roseus L. (Apocyanaceae), Cinnamomum burmani Blume (Lauraceae), Citrus aurantium L. (Rutaceae), Citrus paradisi Macfad. (Rutaceae), Crataegus oxyacantha Rehd. (Rosaceae), Curcuma longa L. (Zingiberaceae), Echinacea angustifolia DC. (Asteraceae), Echinacea pallida Nutt. (Asteraceae), Echinacea purpurea Moench. (Asteraceae), Eleutherococcus senticosus Maxim. (Araliaceae), Foeniculum vulgare P. Mill. (Apiaceae), Gingko biloba L. (Ginkoaceae), Glycine max Merr. (Fabaceae), Hydrastis Canadensis L. (Ranunculaceae), Hypericum perforatum L. (Clausiaceae), Hypoxis hemerocallidea L. (lridaceae), Matricaria recutita L., (Asteraceae), Melaleuca leucadendra L. (Myrtaceae), Oenothera biennis L. (Onagraceae), Panax quinquefolius L. (Araliaceae), Piper methysticum G. Forst. (Piperaceae), Piper nigrum L. (Piperaceae), Salvia miltiorrhiza L. (Lamiaceae), Serenoa repens Small (Arecaceae), Serenoa serrulata Nichols (Arecaceae), Silybum marianum Gaertn. (Asteraceae), Strychnos ligustrina Zipp. (Loganiaceae), Sutherlandia frutescens R. Br. (Fabaceae), Tinospora crispa Hook. f. & Thomson (Menispermaceae), Uncaria tomentosa Roxb. (Rubiaceae), Valeriana officinalis L. (Valerianaceae), Vitis vinifera L (Vitaceae), and Zingiber cassumunar Roxb. (Zingiberaceae), Zingiber officinale Roscoe (Zingiberaceae), and a constituent isolated from said modulator. 6. The method of claim 3 wherein said constituent is a purified or non-purified compound selected from the group consisting of actein, aescin, ajmalicine, allicin, berberine, bergamottin, bergapten, bilobalide, catechin, cimiracemosides A-F, cis-linoleic acid, curcumin, desmethoxyyangonin, dihydrokavain, dihydromethysticin, fatty acid ester, genistein, guar gum, ginkolic acid I and II, 3,3',4',5,6,7,8-heptamethoxyflavone, hydrastine, hyperforin, I3, II8-biapigenin, isobergapten, isorhemnetin, kaempferol, kavain, limonin, methysticin, naringenin, naringin, nobiletin, obacunone, oleanolic acid, pectin, piperine, quercetin, quinidine, S-allyl-L-cysteine, serpentine, silibinin, silichristin, silidianin, silybin, S-methyl-L-cysteine, sodium butyrate, tangeretin, taxifolin, ursolic acid, valerenic acid, vindoline, vintexin, 6,7-dihydroxybergamottin, and yangonin, said constitutent incorporated into said composition in amount from about 0.01 to about 750 mg. 7. The composition of claim 1 wherein said composition further comprises a lipophilic carrier, a hydrophilic carrier, a mucoadhesive agent, a penetration enhancer, a sorption promoter, a solubilizing agent, antioxidant, buffer, plasticizer, lubricant, filler, stabilizer or emulsifier, alone or in combination. 8. The composition of claim 7 formulated as a suppository, gel, spray, film, foam, sponge, cream, tablet, capsule, emulsion, solution, lotion, suspension, particles, microparticles or bioadhesive microparticles. 9. The composition of claim 8 incorporated into, attached to, covering a vaginal device or a device insertable into an oral cavity, or is in contact with said device. 10. The composition of claim 9 wherein said vaginal device is a tampon, tampon-like device, ring, pessary, sponge, foam, tablet or pellet and wherein said device insertable into the oral cavity is a pellet, tablet, foam, film, pillow or strip. 11. The composition of claim 6 comprising the anti-viral agent darunavir, or the anti-cancer agent paclitaxel, each alone or in combination. 12. The composition of claim 11 administered vaginally or into an oral cavity in a therapeutically effective amount wherein said darunavir or paclitaxel is present in from about 0.001 to 3000 mg. 13. The composition of claim 12 formulated as a suppository, gel, spray, film, foam, sponge, cream, tablet, capsule, emulsion, solution, lotion, suspension, particles, microparticles or bioadhesive microparticles and administered vaginally or is incorporated into, attached to or covering a vaginal device, wherein said vaginal device is a tampon, tampon-like device, ring, pessary, sponge, foam, tablet or pellet. 14. The composition of claim 13 further comprising diethylene glycol monobutyl ester. 15. The composition of claim 14 further comprising a lipophilic carrier, a hydrophilic carrier, a mucoadhesive agent, a penetration enhancer, a sorpotion promoter, a solubilizing agent, antioxidant, buffer, plasticizer, lubricant, filler, stabilizer or emulsifier, alone or in combination. 16. The composition of claim 12 formulated as a gel, spray, film, foam, sponge, cream, tablet, capsule, emulsion, solution, lotion, suspension, particles, microparticles or bioadhesive microparticles and administered into an oral cavity or is incorporated into, attached to or covering a device insertable into the oral cavity, or is in contact with said device wherein said insertable device is a pellet, tablet, foam, film, pillow or strip. 17. The composition of claim 16 further comprising diethylene glycol monobutyl ester. 18. The composition of claim 17 wherein said composition further comprises a lipophilic carrier, a hydrophilic carrier, a mucoadhesive agent, a penetration enhancer, a sorption promoter, a solubilizing agent, antioxidant, buffer, plasticizer, lubricant, filler, stabilizer or emulsifier; alone or in combination. 19. The composition of claim 1 wherein said non-ionizable glycol ether is present in an amount of from 0.5 to 10%, by weight. 20. The composition of claim 8 wherein said at least one anti-viral or one anti-cancer agent is present in an amount from about 0.01 to about 3000 mg. 21. The composition of claim 1 wherein said anti-viral drug is selected from the group consisting of GSK-873, PRO-542, SCH-417690, TMC278, TNX-355, .alpha.-epibromide, Abacavir, Aldesleukin, Alovudine, Amdoxovir, Amprenavir, Capravirine, Cidifovir, Darunavir, Delavirdine, Dexelvucitabine, Didanosine, Elvucitabine, Emtricitabine, Enfuvirtide, Erythropeoietin, Etravirine, Fosamprenavir, Hydroxyurea, Indinavir, Lamivudine, Lopinavir, Maraviroc, Nelfinavir, Nevirapine, Ritonavir, Saquinavir, Somatropin, Stavudine, Tenofovir, Tipranavir, Zalcitabine, Zidovudine, AK602, AMD070, BMS-378806, INCB9471, Pro 140, SP01A, Vicriviroc, Gilead 9137, JTK-303, MK-0518, PA457, Panacos ADA, NSC 674447 and HGTV4. 22. The composition of claim 1 wherein said anti-cancer agent is selected from the group consisting of Amsacrine, Bleomycin, Busulfan, Capecitabine, Carboplatin, Carmustine, Chlorambucil, Cisplatin, Cladribine, Crisantaspase, Cyclophosphamide, Cytarabine, Dacarbazine, Dactinomycin, Daunorubicin, Docetaxel, Doxorubicin, Epirubicin, Etoposide, Floxuridine, Fludarabine, Fluorouracil, Gemcitabine, Idarubicin, Ifosfamide, Irinotecan, Leucovorin, Lomustine, Melphalan, Mercaptopurine, Mesna, Methotrexate, Mitomycin, Mitoxantrone, Oxaliplatin, Paclitaxel, Pemetrexed, Pentostatin, Procarbazine, Raltitrexed, Streptozocin, Temozolomide, Teniposide, Thiotepa, Thioguanine, Topotecan, Trimetrexate, Vinblastine, Vincristine, Vindesine, Vinorelbine, Mechlorethamine, Ara-CMP, and Camptothecin.

Details for Patent 8,178,123

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	06/23/1987		2021-08-29
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	10/16/1986		2021-08-29
Eli Lilly And Company	HUMATROPE	somatropin	For Injection	019640	02/04/1999		2021-08-29
Emd Serono, Inc.	SAIZEN	somatropin	For Injection	019764	10/08/1996		2021-08-29