Crystalline diacylhydrazine and the use thereof

Patent metadata

Field	Value
Publication number	US-10501405-B2
Application number	US-201715398236-A
Country	US
Kind code	B2
Filing date	Jan 4, 2017
Priority date	Sep 8, 2011
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

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 Form V, Form VI, Form VII, Form VIII, or Form IX wherein:
Form V is characterized as having a powder x-ray diffraction pattern with peaks at 9.38, 12.22, 13.18, 14.98, 17.32, 18.40, 22.41, 23.40, 23.55, 24.63, 24.79, 25.61, 28.02, and 31.77 degrees 2Θ;
Form VI is characterized as having a powder x-ray diffraction pattern with peaks at 9.38, 12.23, 13.25, 17.48, 18.41, and 22.41 degrees 2Θ;
Form VII is characterized as having a powder x-ray diffraction pattern with peaks at 8.18, 9.71, 13.30, 16.22, 17.73, 20.98, 21.20, 22.76, 24.68, 26.72, and 29.39 degrees 2Θ;
Form VIII is characterized as having a powder x-ray diffraction pattern with peaks at 10.05, 10.77, 14.06, 16.76, 18.11, 18.32, 18.43, 20.89, 21.71, 21.87, 24.07, 24.90, and 28.71 degrees 2Θ; and
Form IX is characterized as having a powder x-ray diffraction pattern with peaks at 7.06, 15.74, and 18.71 degrees 2Θ.

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

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

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

5. The composition of claim 4 , wherein said one or more excipients comprise one or more pharmaceutically acceptable excipients.

6. The composition of claim 5 , wherein said one or more pharmaceutically acceptable excipients comprise Miglyol 812, phospholipon 90G, or tocopheryl polyethylene glycol 1000 succinate, or a mixture thereof.

7. The composition of claim 6 , wherein said one or more pharmaceutically acceptable excipients consist essentially of Miglyol 812, phospholipon 90G, and tocopheryl polyethylene glycol 1000 succinate.

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 of claim 1 .

9. A kit comprising the composition of claim 4 .

Assignees

• Intrexon Corp

Inventors

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

Classifications

• 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

• A61P7/06

  Antianaemics · CPC title

• A61P7/00

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