US 6,982,091 B2
Vaginal delivery of chemotherapeutic agents and inhibitors of membrane efflux systems for cancer therapy
Giovanni M. Pauletti, Loveland, Ohio (US); James H. Liu, Cincinnati, Ohio (US); Leslie Z. Benet, Belvedere, Calif. (US); and Wolfgang A. Ritschel, Cincinnati, Ohio (US)
Assigned to UMD, Inc., Cincinnati, Ohio (US)
Filed on Aug. 21, 2002, as Appl. No. 10/226,667.
Claims priority of provisional application 60/315877, filed on Aug. 29, 2001.
Prior Publication US 2003/0049302 A1, Mar. 13, 2003
This patent is subject to a terminal disclaimer.
Int. Cl. A61F 6/06 (2006.01); A61F 13/02 (2006.01); A61K 9/50 (2006.01)
U.S. Cl. 424—430 33 Claims
OG exemplary drawing
 
1. A method for a transmucosal delivery of chemotherapeutic agents and inhibitors of membrane efflux systems to a systemic circulation for treatment, control and maintenance of cancer in a human female patient, wherein said agents and inhibitors are delivered into the systemic circulation transmucosally through a vaginal mucosa from a mucoadhesive composition or from an intravaginal device incorporated with said composition, said method comprising steps of:
a) providing the transmucosal vaginal composition consisting essentially of from about 0.001 to about 3000 mg of a chemotherapeutic agent selected from the group consisting of daunorubicin, doxorubicin, idarubicin, amrubicin, pirarubicin, epirubicin, mitoxantrone, etoposide, teniposide, vinblastine, vincristine, mitomycin C, paclitaxel, docetaxel, actinomycin D, colchicine, topotecan, irinotecan and gemcitabine or an inhibitor of a membrane efflux system selected from the group consisting of cyclosporin, verapamil, valspodor, biricodar, quinidine, terfenadine, pervilleine A, GF120918, LY335979, OC144-093, XR9576, probenecid, MK571 and a mixture thereof;
from about 30 to about 95% of a lipophilic or hydrophilic carrier selected from the group consisting of saturated mono-, di- or triglyceride of fatty acids from 8 to 18 carbons, a mixture thereof, polyethylene glycol of molecular weight between about 200 and 8000, a derivative thereof and a mixture thereof; from about 5 to about 25% of a mucoadhesive agent selected from the group consisting of a cellulose derivative, natural gum, alginate and pectin; and from about 5 to about 25% of a sorption promoter selected form the group consisting of a non-ionizable glycol ester derivative, a non-ionizable glycol ether derivative and an interesterified stone oil;
wherein said composition is formulated as, or incorporated into the device as, a suppository, cream, gel, foam, ointment, microparticles, microcapsules, nanoparticles or a capsule containing microparticles, microcapsules or nanoparticles, or a liposome suspension; and
b) delivering said composition to the vaginal mucosa by administering said composition into the vagina or inserting said device incorporated with said composition into the vagina
wherein said vaginal device is a vaginal tampon, vaginal ring, vaginal strip, vaginal capsule, vaginal tablet, vaginal pessary, vaginal cup or vaginal sponge.