THERAPEUTIC MODULATION OF VAGINAL EPITHELIUM BOUNDARY LUBRICATION

• US 20120052077A1
• Filed: 01/13/2010
• Published: 03/01/2012
• Est. Priority Date: 01/13/2009
• Status: Active Grant

• Current Assignee: Lubris, LLC, Schepens Eye Research Institute
• Original Assignee: Lubris, LLC
• Inventors: Sullivan, Benjamin, Truitt, Edward R. III, Sullivan, David
• Granted Patent: US 8,980,840 B2
• Time in Patent Office: Days
• US Class Current: 424/158.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61K 38/13 Cyclosporins
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 38/20 Interleukins [IL]
• CPC Class Codes: A61K 38/24 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• 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 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 15/14 for lactation disorders, e.g. galactorrhoea
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 5/26 : Androgens
• CPC Class Codes: A61P 5/30 : Oestrogens

Abstract

The present invention relates to the management of vaginal health. In particular, the present invention relates to pharmaceutical compositions, and methods of use thereof, for treating diseases associated with compromised boundary lubrication at the vaginal epithelium.

Claims

1-27. -27. (canceled)

28. A method of treating decreased vaginal boundary lubrication or a disease associated therewith or of improving vaginal boundary lubrication, the method comprising topically administering to a vaginal surface of a subject in need thereof a therapeutically effective amount of isolated or purified PRG4.

30. The method of claim 28, wherein the disease associated with decreased vaginal boundary lubrication is vaginal atrophy, dyspareunia, Sjö

gren'"'"'s syndrome, menopause, androgen deficiency, estrogen deficiency, estrogen replacement therapy, allergy, chronic inflammation, menopause, premature menopause, chemotherapy, breastfeeding, surgical removal of the ovaries before menopause, genital lichen sclerosis, vulvodynia, bacterial vaginosis, herpes, candida, psoriasis, contact dermatitis, condylomata, or side effects of medications and aging.

29. (canceled)

31-32. -32. (canceled)

33. A method of providing lubrication during intercourse or promoting conception comprising topically administering to a vaginal surface, a penile surface, or a combination thereof an effective amount of an isolated or purified PRG4.

34-35. -35. (canceled)

36. A method for improving vaginal boundary lubrication comprising administering a therapeutically effective amount of isolated or purified PRG4 and a pharmaceutically acceptable carrier, wherein the therapeutically effective amount of isolated or purified PRG4 is sufficient to improve vaginal boundary lubrication.

37. The method of claim 36, wherein the PRG4 is formulated in a gel, an aqueous osmotically balanced salt solution, a multiphasic emulsification, or a slow- or extended-release device.

38. The method of claim 36, wherein the therapeutically effective amount of PRG4 is in a concentration of 10-10,000 μ

g/mL.

39. The method of claim 36, wherein the PRG4 has an average molar mass of between 50 kDa and 400 kDa.

40. The method of claim 36, wherein the PRG4 comprises a lubricating fragment, multimer, or a homolog thereof.

41. The method of claim 36, wherein the PRG4 is a recombinant PRG4 protein or a functional fragment thereof, or a purified naturally occurring PRG4 protein.

42. The method of claim 36, further comprising administering a therapeutic agent selected from the group consisting of an androgen or androgen analogue, selective androgen receptor modulator, selective estrogen receptor modulator, estrogen antagonist, aromatase inhibitor, antiprotease, proinflammatory cytokine antagonist, cytokine release inhibitor, anti-inflammatory cytokine, anti-inflammatory agent, NF-κ

B inhibitor, proteasome inhibitor, hyaluronic acid, neutral or polar lipids, fatty acids, estrogen or estrogen analogue, oestradiol, progesterone, follicle stimulating hormone, leutinizing hormone, sodium hyaluronate, hyaluronic acid, nitric oxide, and amino acid.

43. The method of claim 42, wherein said androgen or androgen analogue is a 17α

methyl-17β

-hydroxy-2-oxa-5α

-androstan-3-one derivative, a testosterone derivative, 4,5α

-dihydrotestosterone derivative, a 17β

-hydroxy-5α

-androstane derivative containing a ring A unsaturation, a 19-nortestosterone derivative, a nitrogen-substituted androgen, a structural subclass of androgens comprising androgenic compounds with unusual structural features, or a combination thereof.

44. The method of claim 42, wherein said selective androgen receptor modulator is an aryl-propionamide compound, a bicyclic hydantoin analogue, a quinoline analogue, or a tetrahydroquinoline analogue.

45. The method of claim 42, wherein said proinflammatory cytokine antagonist is an anti-TNFα

antibody, a soluble TNFα

receptor, or an IL-1 receptor antagonist.

46. The method of claim 42, wherein said anti-inflammatory agent is cyclosporine A, omega 3 fatty acids, or omega 6 fatty acids.

47. The method of claim 42, wherein the amino acid is L-Arginine, citrulline, or aspartic acid.

48. The method of claim 42, wherein the composition comprises sodium hyaluronate or hyaluronic acid in a concentration of 10-100,000 μ

g/mL.

49. The method of claim 42, wherein the composition comprises sodium hyaluronate or hyaluronic acid in a concentration of 500-5,000 μ

g/mL.