Compositions and methods for treating exocrine gland atrophy

• US 5,639,743 A
• Filed: 06/30/1994
• Issued: 06/17/1997
• Est. Priority Date: 11/13/1992
• Status: Expired due to Term

• Current Assignee: The University of Georgia Research Foundation, Inc., University of Southern California
• Original Assignee: The University of Georgia Research Foundation, Inc., University of Southern California
• Inventors: Mircheff, Austin K., Warren, Dwight W., Kaswan, Renee
• Primary Examiner(s): Criares, Theodore J.
• Application Number:
  US08/268,971
• Time in Patent Office: 1,083 Days
• Field of Search: 514/250, 514/254, 514/177, 514/171, 514/410
• US Class Current: 514/10.2
• 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 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2257 Prolactin

Abstract

Methods and compositions for the prevention or reversal of exocrine gland atrophy, especially lacrimal gland atrophy, by maintaining normal physiological levels of prolactin are described. In the preferred embodiment, exogenous prolactin or a substance that modulates endogenous prolactin secretion is administered to a mammal in combination with an androgen, such as testosterone. The combination acts synergistically to maintain or restore normal prolactin concentrations, resulting in the maintenance or restoration of gland mass and function. Administration of prolactin and androgen in combination with estrogen is particularly useful in the treatment of lacrimal gland dysfunction in post-menopausal women or women who have undergone ovariohysterectomies.

Claims

1. A method of preventing or reversing secretory exocrine gland atrophy in a mammal comprising administering to the mammal in need thereof a synergistic amount effective to prevent or reverse secretory exocrine gland atrophy of the combination of a compound modulating endogenous prolactin levels and an androgen selected from the group consisting of testosterone and dihydrotestosterone, wherein the secretory exocrine gland is selected from the group consisting of salivary glands, lacrimal glands, mucus-secreting glands, glands of the gastrointestinal system, glands of the urinary system, and vaginal glands.

2. The method of claim 1 wherein the combination of the prolactin modulating compound and the androgen is effective to increase lacrimal gland function.

3. The method of claim 1 wherein the prolactin modulating compound is selected from the group consisting of isolated prolactin and recombinant prolactin.

4. The method of claim 1 wherein the prolactin modulating compound is a compound capable of modulating endogenous pituitary prolactin secretion.

5. The method of claim 4 wherein the compound modulating prolactin secretion is selected from the group consisting of prolactin secretion stimulants and inhibitors.

6. The method of claim 1 wherein the combination of the prolactin modulating compound and the androgen is administered subcutaneously.

7. The method of claim 6 wherein the combination of the prolactin modulating compound and the androgen is administered via a controlled release implant.

8. The method of claim 1 wherein the combination of the prolactin modulating compound and the androgen is administered orally.

9. The method of claim 1 wherein the combination of the prolactin modulating compound and the androgen is administered intramuscularly.

18. The method of claim 1, wherein the compound modulating endogenous prolactin levels is bromocriptine and the androgen is testosterone.

10. A composition for the treatment of secretory exocrine gland atrophy comprising synergistic effective amounts of an androgen selected from the group consisting of testosterone and dihydrotestosterone and a compound modulating endogenous prolactin levels to prevent or reverse atrophy or maintain function of a secretory exocrine gland, wherein the secretory exocrine gland is selected from the group consisting of salivary glands, lacrimal glands, mucus-secreting glands, glands of the gastrointestinal system, glands of the urinary system, and vaginal glands, in a physiologically acceptable carrier.

11. The composition of claim 10 wherein the prolactin modulating compound is selected from the group consisting of isolated prolactin and recombinant prolactin.

12. The composition of claim 10 wherein the androgen is testosterone which is made synthetically.

13. The composition of claim 10 further comprising estrogen or an estrogen analog in an amount effective to increase lubrication of an estrogen target tissue.

15. The composition of claim 10 wherein the prolactin modulating compound is a compound capable of modulating endogenous pituitary prolactin secretion.

16. The composition of claim 15 wherein the compound modulating prolactin secretion is selected from the group consisting of prolactin secretion stimulants and inhibitors.

17. The composition of claim 10 in a controlled release implant.

19. The composition of claim 10, wherein the androgen is testosterone and the compound modulating endogenous prolactin levels is bromocriptine.

14. A composition for the treatment of secretory exocrine gland atrophy comprising an effective amount of the combination of an androgen and a compound modulating endogenous prolactin levels, in a physiologically acceptable carrier, to prevent or reverse atrophy or maintain function of a secretory exocrine gland, wherein the exocrine gland is the lacrimal gland.