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Details for Patent: 5,763,428

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Details for Patent: 5,763,428

Title: Methods of treating skin disorders with novel 1a-hydroxy vitamin D.sub.4 compounds and derivatives thereof
Abstract:The disclosure is of methods of treating various skin disorders, including skin cancer, with compounds of novel 1.alpha.-hydroxy vitamin D.sub.4 and novel analogues, thereof, including 1,25 dihydroxy vitamin D.sub.4 and 1,24 dihydroxy vitamin D.sub.4. Novel 1.alpha.-hydroxy vitamin D.sub.4 compounds and compounds of novel analogues suitable for use in the treatment of such disorders are also disclosed herein.
Inventor(s): Knutson; Joyce C. (Madison, WI), Bishop; Charles W. (Madison, WI)
Assignee: Bone Care International, Inc. (Madison, WI)
Filing Date:Jun 07, 1995
Application Number:08/484,342
Claims:1. A method of inhibiting hyperproliferative activity of human skin cancer cells, comprising treating the cancer cells with an effective amount of a compound of formula (I): ##STR2## wherein R.sub.1 is either H or OH and R.sub.2 is either H or OH and salts, hydrates and solvates thereof.

2. The method of claim 1, wherein said amount is administered without causing hypercalcemia.

3. A method of treating psoriasis, comprising administering to a patient suffering from psoriasis a therapeutically effective amount of a compound of formula (I): ##STR3## wherein R.sub.1 is either H or OH and R.sub.2 is either H or OH and salts, hydrates and solvates thereof.

4. The method of claim 3, wherein said amount is administered without causing hypercalcemia.

5. A method of treating a human to alleviate the cellular proliferative effects of human skin cancer, psoriasis, eczema, dermal hydration and sebum secretion, said method comprising administering to the human a therapeutically effective amount of a compound of formula (I): ##STR4## wherein R.sub.1 is either H or OH and R.sub.2 is either H or OH and salts, hydrates and solvates thereof.

6. The method of claim 5, wherein said amount is administered without causing hypercalcemia.

7. The method of any one of claims 1, or 3, or 5 wherein the compound of formula (I) is 1.alpha.,24-dihydroxy vitamin D.sub.4.

8. The method of any one of claims 1, 3, or 5 wherein the compound of formula (I) is 1.alpha.,24(R)-dihydroxy vitamin D.sub.4, substantially free of its (S) form.

9. The method of any one of claims 1, 3, or 5 wherein said amount is administered topically.

10. The method of claim 9, wherein said administering step further comprising administering a second agent selected from the group consisting of retinoids, chromanols, .beta.-agonists, antiinflammatory agents, keratoplastic agents and combinations thereof.

11. The method of any one of claims 1, 3, or 5 wherein said amount is administered orally.

12. The method of any one of claims 1, 3, or 5 wherein said amount is administered parenterally.

13. A method of inhibiting hyperproliferative activity of human skin cancer cells, comprising treating the cancer cells with an effective amount of a compound of formula (I): ##STR5## wherein R.sub.1 is either H or OH and R.sub.2 is either H or OH and salts, hydrates and solvates thereof, wherein said inhibiting of proliferative activity is measured by inhibition of thymidine uptake by said cancer cells.

14. A method of inhibiting hyperproliferative activity of human skin cancer cells, comprising treating the cancer cells with an effective amount of a compound of formula (I); ##STR6## wherein R.sub.1 is either H or OH and R.sub.2 is either H or OH and salts, hydrates and solvates thereof, wherein said treating step comprises exposing skin cancer cells to an amount of 1.alpha.,24-dihydroxyvitamin D.sub.4 sufficient to induce differentiation of said cancer cells to nonmalignant macrophages.

15. The method of claim 14 wherein said cells are human keratinocytes.

16. The method of any one of claims 13 or 14 wherein the compound of formula (I) is 1.alpha.,24-dihydroxy vitamin D.sub.4.

17. The method of any one of claims 13 or 14 wherein the compound of formula (I) is 1.alpha.,24(R)-dihydroxy vitamin D.sub.4, substantially free of its (S) form.

18. The method of any one of claims 13 or 14 wherein said amount is administered topically.

19. The method of claim 18, wherein said administering step further comprising administering a second agent selected from the group consisting of retinoids, chromanols, .beta.-agonists, antiinflammatory agents, keratoplastic agents and combinations thereof.

20. The method of any one of claims 13 or 14 wherein said amount is administered orally.

21. The method of any one of claims 13 or 14 wherein said amount is administered parenterally.
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