FORMULATION FOR LIPOPHILIC AGENTS

• US 20100197641A1
• Filed: 09/03/2009
• Published: 08/05/2010
• Est. Priority Date: 09/18/2002
• Status: Abandoned Application

• Current Assignee: Creighton Reed Goldensoph, Jeffrey W. Driscoll, Leon W. Levan, Richard B. Mazess
• Original Assignee: Creighton Reed Goldensoph, Jeffrey W. Driscoll, Leon W. Levan, Richard B. Mazess
• Inventors: LeVan, Leon W., Goldensoph, Creighton Reed, Driscoll, Jeffrey W., Mazess, Richard B.
• Application Number:
  US12/553,547
• Publication Number:
  US 20100197641A1
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61K 31/592 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/18 of the parathyroid hormones

Abstract

The invention relates to pharmaceutical formulations of lipophilic therapeutic agents in which such agents are solubilized in largely aqueous vehicles, and processes for preparing and using the same.

Claims

1. A formulation, comprising a vitamin D compound;

a non-ionic solubilizer selected from the group consisting of polyoxyalkylenes, polysorbate 20, fatty acid esters of glycerol, cyclodextrins, dextrans, and fatty alcohol ethers of oligoglucosides;

a lipophilic antioxidant selected from the group consisting of butylated hydroxytoluene (BHT), lipoic acid, lycopene, lutein, lycophyll, xanthophyll, carotene, zeaxanthin, vitamin E and esters thereof; and

an aqueous vehicle.

2. A formulation as set forth in claim 1, wherein the lipophilic antioxidant is present in a concentration of 20 to 2000 ppm.

3. A formulation as set forth in claim 1, wherein the non-ionic solubilizer is present in a concentration of 0.05 to 5% w/w.

4. A formulation as set forth in claim 1, wherein the formulation is suitable for parenteral administration.

5. A formulation as set forth in claim 1, further comprising an optional agent which is an organic solvent, a preservative or both.

6. A formulation as set forth in claim 5, wherein the optional agent includes benzyl alcohol and ethanol.

7. A formulation as set forth in claim 6, wherein the optional agent includes ethanol.

8. A formulation as set forth in claim 6, wherein the optional agent includes benzyl alcohol.

9. A formulation as set forth in claim 6, wherein the optional agent is present in a concentration of 0 to 30% w/w.

10. A formulation as set forth in claim 9, wherein the optional agent is present in a concentration of 0% to about 10% w/w.

11. A formulation as set forth in claim 10, wherein the optional agent is present in a concentration of about 1% to about 3% w/w.

12. The formulation of claim 1, wherein the vitamin D compound is selected from the group consisting of 1α

,24-dihydroxyvitamin D₂, 1α

,24-dihydroxyvitamin D₄, 1α

,25-dihydroxyvitamin D₃, 1α

-hydroxyvitamin D₃, 1α

, 25-dihydroxyvitamin D₂, 1α

,25-dihydroxyvitamin D₄, and 1α

,24,25-dihydroxyvitamin D₂, seocalcitol, calcipotriol, maxacalcitol, falecalcitriol, paricalcitol.

13-25. -25. (canceled)

26. A parenteral formulation, comprising a vitamin D compound, 0.05 to 5% w/w of a non-ionic solubilizer non-ionic selected from the group consisting of polyoxyalkylenes, polysorbate 20, fatty acid esters of glycerol, cyclodextrins, dextrans, and fatty alcohol ethers of oligoglucosides;

and 20 to 2000 ppm of a lipophilic antioxidant selected from the group consisting of butylated hydroxytoluene (BHT), lipoic acid, lycopene, lutein, lycophyll, xanthophyll, carotene, zeaxanthin, vitamin E and esters thereof.

27. A formulation as set forth in claim 26, further comprising an optional agent.

28. A formulation as set forth in claim 27, wherein the non-ionic solubilizer includes 0.5%-2.5% w/w polysorbate-20, the lipophilic antioxidant includes 20 ppm BHT and the optional agent includes 2.5% w/w ethanol.

29. A formulation as set forth in claim 27, wherein the non-ionic solubilizer includes 0.5%-2.5% w/w polysorbate 20, the lipophilic antioxidant includes 20 ppm BHT and the optional agent includes 2.5% w/w benzyl alcohol.

30-45. -45. (canceled)