Crystalline diacylhydrazine and the use thereof

Patent metadata

Field	Value
Publication number	US-8946294-B2
Application number	US-201213606444-A
Country	US
Kind code	B2
Filing date	Sep 7, 2012
Priority date	Sep 8, 2011
Publication date	Feb 3, 2015
Grant date	Feb 3, 2015

Abstract

The present disclosure provides crystalline polymorphic and amorphous forms of (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 1) or (S)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide (Compound 2). The present disclosure further provides compositions comprising crystalline polymorphic and amorphous forms of Compound 1 or Compound 2 and an excipient, methods of making crystalline polymorphic or amorphous forms of Compound 1 or Compound 2, and methods of using crystalline polymorphic or amorphous forms of Compound 1 or Compound 2 to regulate gene expression in a cell or in a subject.

First claim

What is claimed is:

1. Crystalline (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide
characterized as having a powder x-ray diffraction pattern with peaks at 8.14, 8.52, 9.62, 11.02, 11.90, 12.16, 14.02, 14.62, 17.00, 17.88, 18.56, 19.02, 19.24, 20.51, 20.93, 22.19, 22.73, 23.22, 24.31, 24.53, 25.91, 26.22, 27.36, 27.73, 28.70, 30.84, 31.52, 32.30, 33.19, and 34.39 degrees 2Θ.

2. The crystalline (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide Form III of claim 1 , further characterized as being substantially pure.

3. The crystalline (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide Form III of claim 2 , further characterized as being pure.

4. The crystalline (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide Form III of claim 1 having an average particle size distribution of about 10 μm or less.

5. A composition comprising the crystalline (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide Form III of claim 1 and one or more excipients.

6. The composition of claim 5 , wherein said one or more excipients comprise one or more pharmaceutically acceptable excipients.

7. The composition of claim 6 , wherein said one or more pharmaceutically acceptable excipients comprise Miglyol 812, phospholipon 90G, or tocopheryl polyethylene glycol 1000 succinate, or a mixture thereof.

8. A kit comprising the crystalline (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl)-N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide Form III of claim 1 .

9. The crystalline (R)-3,5-dimethyl-benzoic acid N-(1-tert-butyl-butyl) -N′-(2-ethyl-3-methoxy-benzoyl)-hydrazide Form III of claim 4 having an average particle size distribution of about 1 μm or less.

Assignees

• Hormann Robert E
• Shulman Inna
• Rödel Eva
• Hilfiker Rolf
• De Paul Susan M
• Intrexon Corp

Inventors

• Hormann Robert E
• Shulman Inna
• Rödel Eva
• Hilfiker Rolf
• De Paul Susan M

Classifications

• A61P7/06

  Antianaemics · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title