Use of vitamin D glycosides, vitamin D orthoester glycosides, vitamin D analog glycosides and vitamin D analog orthoester glycosides for the treatment of osteoporosis

• US 5,508,392 A
• Filed: 04/20/1994
• Issued: 04/16/1996
• Est. Priority Date: 12/29/1992
• Status: Expired due to Fees

• Current Assignee: Michael F. Holick
• Original Assignee: Michael F. Holick
• Inventors: Holick, Michael F.
• Primary Examiner(s): GRIFFIN, RONALD
• Application Number:
  US08/230,867
• Time in Patent Office: 727 Days
• Field of Search: 514/35, 514/167, 514/171, 568/665, 568/817, 568/819, 536/4.1, 536/18.1, 536/17.2, 536/55.2, 536/53
• US Class Current: 536/18.1
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention relates to methods for the treatment of prevention of osteoporosis by the administration of a vitamin D glycoside or vitamin D orthoester glycoside, or an analog thereof.

Claims

1. A method for treating or preventing osteoporosis in an individual having osteoporosis or susceptible to osteoporosis without causing the side effects associated with the administration of 1,25-dihydroxyvitamin D₃, comprising administering to said individual an effective amount of a compound having the formula:

##STR8## wherein the bond between C-22 and C-23 is a single bond or a double bond;

Y² is hydrogen, fluorine, methyl, ethyl or OR¹ ;

Z² is F, H or X² ;

U is hydrogen, --OH or --O--(C₂ -C₄ alkyl)--OH;

Q^a is CF₃ or CH₂ X² ;

Q^b is CF₃ or CH₃ ;

R is a double bond or an epoxy group;

X¹ and X² are selected from the group consisting of hydrogen and OR¹ ;

R¹ is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue, or R¹ is an orthoester glycoside moiety of the formula;

##STR9## wherein A represents a glycothranosyl or glycopyranosyl ring;

R² is hydrogen, alkyl (C₁ -C₄), aralkyl (C₇ -C₁₀), or aryl, with the proviso that aryl is phenyl or phenyl substituted by chloro, fluoro, bromo, iodo, C₁ -C₄ alkyl, C₁ -C₄ alkoxy;

or naphthyl;

R³ is hydrogen or a straight or branched chain glycosidic residue containing 1-20 glycosidic units per residue;

W is CH--CH₃ or O; and

V is CH₂ or O;

with the proviso that both W and V are not both O; and

"═

═

═

" is either a single bond between Q^a and Q^b or a hydrogen atom on Q^a and Q^b,

with the proviso that wherein "═

═

═

" is a single bond, then X² is H; and

with the further proviso that at least one of the R¹ groups is either a β

-glycosidic residue or an orthoester β

-glycoside moiety.

2. The method of claim 1, wherein said compound is 1,25(OH)₂ D₃ -3β

-glucoside.

3. The method of claim 1, wherein said compound is administered in an amount ranging from about 0.1 to 100 micrograms/kg per day.

4. The method of claim 1, wherein said compound is administered as part of a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

5. The method of claim 1, wherein said individual is suffering from or has suffered from menopause.

6. The method of claim 1, wherein said compound is administered to a woman prior to the onset of menopause.