Localized vaginal delivery without detrimental blood levels

• US 20040234606A1
• Filed: 02/17/2004
• Published: 11/25/2004
• Est. Priority Date: 09/12/1997
• Status: Abandoned Application

• Current Assignee: Columbia Laboratories, Inc. (Catalent, Inc.)
• Original Assignee: Columbia Laboratories, Inc. (Catalent, Inc.)
• Inventors: Levine, Howard L., Bologna, William J., De Ziegler, Dominique
• Application Number:
  US10/778,151
• Publication Number:
  US 20040234606A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61P 15/06 Antiabortive agents; Labour repressants
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics

Abstract

The invention relates to a pharmaceutical composition for vaginal administration of a treating agent normally associated with undesired side effects at detrimental blood levels. The composition releases the treating agent at a rate to achieve local tissue concentrations without such detrimental blood levels by using a therapeutically effective amount of the treating agent and a bioadhesive, cross-linked water swellable, but water-insoluble polycarboxylic acid polymer. Using this composition and the method of treatment provides sufficient local levels of the drug to provide therapeutic efficacy, but avoids many untoward adverse events. The invention also relates to a pharmaceutical composition for use during menses that includes a treating agent and a bioadhesive, cross-linked water swellable, but water-insoluble polycarboxylic acid polymer.

Claims

1. A pharmaceutical composition for vaginal administration of a treating agent, other than progesterone or an anti-STD agent, normally associated with potential undesired side effects at detrimental blood levels, to achieve local tissue concentrations without detrimental blood levels of the treating agent, comprising a therapeutically effective amount of said treating agent and a bioadhesive, cross-linked water-swellable but water-insoluble polycarboxylic acid polymer.

3. The composition of claim 1, wherein the treating agent is a prostaglandin.

25. The composition of claim 1, wherein the treating agent is one or more of follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, thryoid-stimulating hormone, estradiol, testosterone, an estrogenic compound, progesterone, tamoxifen, mifepristone, raloxifene, nitroglycerin, isosorbide, erythrityl tetranitrate, pentaerythritol tetranitrate, terbutaline, albuterol, pirbuterol, bitolterol, ritodrine, propranolol, metoprolol, nadolol, atenolol, timolol, esmolol, pindolol, acebutolol, labetalol, morphine, hydromorphone, oxymorphone, codeine, hydrocodone, oxycodone, leverophanol, levallorphan, buprenorphine, fentanyl, nalbuphine, butorphanol, pentazocine, naloxone, nalmefene, misoprostol, diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, mefenamic acid, meloxicam, nabumetone, naproxin, oxaprozin, piroxicam, sulindac, tolmetin, lidocaine, cocaine, chloroprocaine, tetracaine, prilocaine, mepivacaine, buipivacaine, levobupivacaine, articaine, ropivacaine, phenol, benzocaine, pramoxine, dyclonine, etidocaine, procaine, proparacaine, dibucaine, pramoxine, imiquimod, bethanecol, melphalan, fluorouracil, vinca alkaloids, bleomycin, and cisplatin.

2. The composition of claim I, wherein the polymer is polycarbophil.

4. The composition of claim 2, wherein the treating agent is one or more of glycoproteins, sex hormones, anti-hormones, and nitrates.

5. The composition of claim 2, wherein the treating agent is one or more of beta agonists, beta antagonists, opioids, and opioid antagonists.

6. The composition of claim 2, wherein the treating agent is one or more of NSAIDS anti-infectives, proteins, antifungals, anesthetics, immune system modifiers, and anti-neoplastic agents.

8. The method of claim 5, wherein the polymer is polycarbophil.

9. The method of claim 8, wherein the treating agent is a prostaglandin.

7. A method of safely delivering a treating agent, other than progesterone or an anti-STD agent, normally associated with potential undesired side effects at detrimental blood levels to a female subject comprising vaginal insertion of a bioadhesive, cross-linked water-swellable but water-insoluble polycarboxylic acid polymer formulation with a therapeutically effective amount of said treating agent wherein the formulation releases the treating agent at a rate that achieves local tissue concentrations without producing detrimental blood levels of the treating agent.

10. The method of claim 7, wherein the treating agent is is one or more of glycoproteins, sex hormones, anti-hormones, and nitrates.

11. The method of claim 7, wherein the treating agent is one or more of beta agonists, beta antagonists, opioids, and opioid antagonists.

12. The method of claim 7, wherein the treating agent is one or more of NSAIDS, anti-infectives, proteins, anti-fungals, anesthetics, immune system modifiers, and anti-neoplastic agents.

19. The method of claim 12, wherein the polymer is polycarbophil.

20. The method of claim 19, wherein the treating agent is one or more of prostaglandins, glycoproteins, sex hormones, anti-hormones, and nitrates.

21. The method of claim 19, wherein the treating agent is one or more of nitrates, beta agonists, beta antagonists, opioids, and opioid antagonists.

22. The method of claim 19, wherein the treating agent is one or more of NSAIDS, anti-infectives, proteins, and anti-fungals.

26. The method of claim 7, where in the treating agent is one or more of follicle-stimulating hormone, luteinizing hormone, human chorionic gonadotropin, thryoid-stimulating hormone, estradiol, testosterone, an estrogenic compound, progesterone, tamoxifen, mifepristone, raloxifene, nitroglycerin, isosorbide, erythrityl tetranitrate, pentaerythritol tetranitrate, terbutaline, albuterol, pirbuterol, bitolterol, ritodrine, propranolol, metoprolol, nadolol, atenolol, timolol, esmolol, pindolol, acebutolol, labetalol, morphine, hydromorphone, oxymorphone, codeine, hydrocodone, oxycodone, leverophanol, levallorphan, buprenorphine, fentanyl, nalbuphine, butorphanol, pentazocine, naloxone, nalmefene, misoprostol, diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetin, lidocaine, cocaine, chloroprocaine, tetracaine, prilocaine, mepivacaine, buipivacaine, levobupivacaine, articaine, ropivacaine, phenol, benzocaine, pramoxine, dyclonine, etidocaine, procaine, proparacaine, dibucaine, pramoxine, imiquimod, bethanecol, melphalan, fluorouracil, vinca alkaloids, bleomycin, and cisplatin.

13. A pharmaceutical composition for vaginal administration of a treating agent during menses, comprising a bioadhesive, cross-linked water-swellable but water-insoluble polycarboxylic acid polymer and a therapeutically effective amount of a treating agent.

14. The composition of claim 13, wherein the polymer is polycarbophil.

15. The composition of claim 13, wherein the treating agent is one or more of prostaglandins, glycoproteins, sex hormones, anti-hormones, and nitrates.

16. The composition of claim 13, wherein the treating agent is one or more of nitrates, beta agonists, beta antagonists, opioids, and opioid antagonists.

17. The composition of claim 13, wherein the treating agent is one or more of NSAIDS, anti-infectives, proteins, or anti-fungals.

27. The composition of claim 13, wherein the treating agent is one or more of gonadotropin-releasing hormone, oxytocin analogs, somatostatin analogs, tissue plasminogen activator, growth hormone releasing hormone, corticotropin-releasing hormone analogs, and anti-fungals.

18. A method of extended vaginal delivery of a treating agent during menses to a patient, comprising vaginal insertion of a bioadhesive, cross-linked water-swellable but water-insoluble polycarboxylic acid polymer formulation with a therapeutically effective amount of said treating agent.

23. The method of claim 18, wherein the formulation is administered at most every two days.

24. The method of claim 23, wherein the formulation is administered twice a week.