Coated vaginal device for delivery of anti-migraine and anti-nausea drugs

• US 7,744,916 B2
• Filed: 05/10/2005
• Issued: 06/29/2010
• Est. Priority Date: 06/11/1997
• Status: Expired due to Fees

• Current Assignee: Femina Pharma Incorporated
• Original Assignee: Umd, Inc.
• Inventors: Kishorkumar, Desai J., Ritschel, Wolfgang A., Soderstrom, Richard, Wilson, Michelle, Pauletti, Giovanni M.
• Primary Examiner(s): Azpuru; Carlos A
• Application Number:
  US11/126,863
• Publication Number:
  US 20050249774A1
• Time in Patent Office: 1,876 Days
• Field of Search: None
• US Class Current: 424/433
• CPC Class Codes: A61F 13/2051 characterised by the material or the structure of the inner absorbing core
• CPC Class Codes: A61F 6/06 for use by females A61F6/20 takes precedence
• CPC Class Codes: A61F 6/08 Pessaries, i.e. devices worn in the vagina to support the uterus, remedy a malposition or prevent conception , e.g. combined with devices protecting against contagion
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/0036 Devices retained in the vagina or cervix for a prolonged period, e.g. intravaginal rings, medicated tampons, medicated diaphragms
• CPC Class Codes: A61K 9/02 Suppositories; Bougies; Bases therefor; Ovulesapparatus for making A61J3/08; devices for introducing into the body A61M31/00
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

A vaginal device for delivery of an anti-migraine or anti-nausea drug to the uterus and/or to the general circulation through vaginal mucosa. The device is at least partially coated with one or several layers of fluid impermeable material forming a cap, film, foam, foil or strip incorporated with mucoadhesive composition comprising the anti-migraine or anti-nausea drug.

Claims

1. A vaginal device for delivering an anti-migraine or anti-nausea drug to a female subject, said device comprising

the vaginal device;

the anti-migraine or anti-nausea drug formulated as a mucoadhesive composition; and

a fluid impermeable coating comprising said composition;

wherein said vaginal device is a tampon, foam, ring, pessary, sponge, cylinder, tablet, capsule, pad, suppository, pellet or tube;

wherein said anti-migraine drug is selected from the group of compounds consisting of ergotamine, dihydroergotamine, ergostine, butalbital, phenobarbital, acetaminophen, diclofenac sodium, ketoprofen, ketorolac, ibuprofen, piroxicam, naproxen, acetylsalicylic acid, flurbiprofen, tolfenamic acid, butorphanol, meperidine, methadone, sumatriptan, naratriptan, razatriptan, zolmitriptan, almotriptan, eletriptan, dexamethasone, hydrocortisone, isometheptene, chlorpromazine, diazepam, droperidol, valproic acid, gabapentin, topiramate and divalproex sodium, each alone or in combination, or in combination with the anti-nausea drug, and

wherein said anti-nausea drug is selected from the group consisting of metoclopramide, prochlorperazine, domperidone, ondansetron, tropisetron, dolasetron, nabilone, dronabinol, levonantradol, aprepitant, cyclizine, promethazine, each alone or in combination or in combination with the anti-migraine drug;

wherein said fluid impermeable coating is a degradable or non-degradable water soluble or non-soluble polymer selected from the group consisting of wax, plastic polymeric film, coated gauze, synthetic polymer, dextran, cellulose, hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, polyethylene glycol, polyethylene, polyethylene oxide, alginate, chitosan, copolymer of ethylene oxide and propylene oxide, polyethylene oxide-co-propylene oxide, polyacrylic acid, collagen, albumin, gelatin, polylactide, polyglycolide, polyethylene terephthalate, polybutyric acid, polyvaleric acid, polylactide-co-caprolactone, polyanhydride, polyorthoester, polyamide, polypropylene, polystyrene, polyvinyl chloride, polymethacrylic acid and a derivative thereof, alone, or in combination,

wherein said coating is attached to said device as a film, foil, sheet, beads or xerogel and is either incorporated into said device, attached to said device or inserted into said device.

2. The device of claim 1 wherein said mucoadhesive composition comprises from about 0.00001 to about 45 mg/kg of body weight of the anti-migraine or anti-nausea drug, from about 0.1 to about 25%, by weight, of a mucoadhesive agent, from about 30 to about 95%, by weight, of a lipophilic or hydrophilic carrier, and from about 5 to about 30% of a sorption promoter.

3. The device of claim 2 wherein said coating is incorporated with said mucoadhesive composition or said composition is attached to said coating.

4. The device of claim 3 wherein said vaginal device is completely or partially coated with said fluid impermeable material.

5. The device of claim 4 wherein said vaginal device is coated with said fluid impermeable material partially at the proximal end.

6. The device of claim 4 wherein said coating comprising said composition is attached to said device and configured to make physical contact with the vaginal mucosa and cervix of the uterus.

7. The device of claim 6 wherein said coating is attached to said device permanently or removably as a cap, cup or strip.

8. The device of claim 7 wherein said cap, cup or strip is attached to said device permanently and wherein said mucoadhesive composition is formulated as a foam, film, suppository, tablet, capsule or capsule containing microparticle or nanoparticle and is attached or inserted into said cap, cup or strip.

9. The device of claim 7 wherein said cap, cup or strip is attached to said device permanently and wherein said mucoadhesive composition is formulated as a solution, powder, cream, lotion, microparticle, nanoparticle, emulsion, liposomal suspension fluid, a bioadhesive system or microemulsion and incorporated into said cap, cup or strip.

10. The device according to claim 3 wherein said mucoadhesive composition comprises from about 0.001 to about 15 mg/kg of body weight the anti-migraine or anti-nausea drug, from about 40 to about 95% of a lipophilic or hydrophilic carrier, from about 1.5 to about 15%, by weight, of the mucoadhesive agent, from about 2 to about 30%, by weight, of sorption promoter and additionally from about 5 to about 30% of a permeation enhancer.

11. The device of claim 10 wherein said mucoadhesive agent is hydroxypropyl methylcellulose, a cellulose derivative, a natural gum, alginate or pectin, wherein said sorption promoter is ethoxydiglycol, polyethylene glycol caprylic/capric glycerides, a glycol derivative with oleic acid esters of propylene glycol and glycerol or interesterified stone oil, wherein the lipophilic carrier is a saturated mono-, di- or triglyceride of fatty acids having carbon chain of from 8 to 18 carbons, or a mixture thereof and wherein the hydrophilic carrier is a polyethylene glycols (PEG) of a molecular weight between about 200 and 8000, or a derivative or mixture thereof, PEG 6000/PEG 1500, PEG 6000/PEG 1500/PEG 400, or PEG 6000/PEG 400, or PEG 8000/PEG 1500.

12. The device of claim 1 wherein said device is a tampon or foam and wherein said fluid impermeable coating material is polyethylene oxide.

13. The device of claim 10 wherein said anti-migraine or anti-nausea drug is ergotamine in the range from about 0.05 to about 1.5 mg/kg, t.i.d., diclofenac sodium from about 0.5 to about 4 mg/kg, b.i.d., sumatriptan from about 0.2 to about 10 mg/kg per day, zolmitriptan from about 0.1 to 7 mg/kg per day, metoclopramide from about 0.1 to 1.0 mg/kg per dose, perchlorperazine from 0.3 to 2.5 mg/kg per dose, ondansetron from about 0.3 to 4 mg/kg per dose, dronabinol from about 0.05 to 0.5 mg/kg, or promethazine from 0.15 to 1.3 mg/kg.