Compositions of crystallized hydrophobic compounds and methods of making and using same

Patent metadata

Field	Value
Publication number	US-10851069-B2
Application number	US-201716091330-A
Country	US
Kind code	B2
Filing date	Apr 4, 2017
Priority date	Apr 4, 2016
Publication date	Dec 1, 2020
Grant date	Dec 1, 2020

Abstract

The present invention provides, in certain embodiments, compositions comprising a uniform population of free, single crystals of a hydrophobic compound. Methods of administering, and processes for preparing, compositions comprising a uniform population of free, single crystals of a hydrophobic compound are also provided.

First claim

What is claimed is:

1. A uniform population of free, single crystals of a compound having chemical formula (I):

or a salt thereof, wherein each free, single crystal in the population has a characteristic dimension of at least about 1 micrometer.

2. The uniform population of free, single crystals of claim 1 , wherein each free, single crystal exhibits the same polymorph.

3. The uniform population of free, single crystals of claim 1 , wherein each free, single crystal has a characteristic dimension of at least about 5 microns.

4. The uniform population of free, single crystals of claim 1 , wherein each free, single crystal has a characteristic dimension of at least about 50 microns.

5. The uniform population of free, single crystals of claim 1 , wherein each free, single crystal has a characteristic dimension of at least about 500 microns.

6. The uniform population of free, single crystals of claim 1 , wherein each free, single crystal has a characteristic dimension of at least about 1 millimeter.

7. A composition comprising a uniform population of free single crystals of claim 1 , and amorphous compound having chemical formula (I), or a salt thereof.

8. A composition comprising a uniform population of free single crystals of claim 1 , and a pharmaceutically acceptable carrier or excipient.

9. A composition comprising a uniform population of free single crystals of claim 1 , wherein the compound having chemical formula (I), or a salt thereof, is encapsulated by a material.

10. A method of delivering to a subject a uniform population of free single crystals of a compound having chemical formula (I):

or a pharmaceutically acceptable salt thereof, comprising:
administering to the subject a uniform population of free single crystals of a compound having chemical formula (I), or a pharmaceutically acceptable salt thereof, wherein each free, single crystal in the population has a characteristic dimension of at least about 1 micrometer,
thereby delivering the uniform population of free single crystals of the compound having chemical formula (I), or a pharmaceutically acceptable salt thereof, to the subject.

11. The method of claim 10 , wherein the subject is a human.

12. A method of treating fibrosis in a subject in need thereof, comprising administering an effective amount of a uniform population of free, single crystals of claim 1 to the subject.

13. The method of claim 10 , wherein the uniform population of free, single crystals is administered to the subject by injection.

14. The method of claim 10 , wherein the uniform population of free, single crystals is administered to the subject by implantation.

15. A polymorph of a compound represented by chemical formula (I):

characterized by at least five major powder x-ray diffraction peaks at 2θ angles selected from 18.42°, 19.46°, 19.88°, 21.4°, 21.64°, 22.22°, 23.82°, 29.64° and 31.08°.

16. The method of claim 12 , wherein the uniform population of free, single crystals is administered by injection.

17. The method of claim 12 , wherein the uniform population of free, single crystals is administered by implantation.

18. The method of claim 12 , wherein the fibrosis is associated with an implanted material.

19. The method of claim 18 , wherein the implanted material is a medical device.

20. A method of treating or preventing a foreign body response to an implanted material in a subject in need thereof, comprising administering an effective amount of a uniform population of free, single crystals of claim 1 to the subject.

Assignees

• Massachusetts Inst Technology

Inventors

• Farah Shady
• Doloff Joshua C
• Langer Robert S
• Anderson Daniel G

Classifications

• A61K31/551

  having two nitrogen atoms, e.g. dilazep · CPC title

• A61K9/0024

  Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L) · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/416

  condensed with carbocyclic ring systems, e.g. indazole · CPC title

• A61K31/519

  ortho- or peri-condensed with heterocyclic rings · CPC title