Therapeutic and imaging compositions and uses thereof

Patent metadata

Field	Value
Publication number	US-10000581-B2
Application number	US-201414889722-A
Country	US
Kind code	B2
Filing date	May 7, 2014
Priority date	May 7, 2013
Publication date	Jun 19, 2018
Grant date	Jun 19, 2018

Abstract

Various embodiments of the present invention are directed to polyrotaxanes comprising a poloxamer core and at least one cyclodextrin and methods for treating Niemann-Pick type C (NPC) and imaging (e.g., MRI) using the polyrotaxanes various embodiments of the present invention.

First claim

What is claimed is:

1. A polyrotaxane comprising a poloxamer core and at least one cyclodextrin comprising a nuclide chelating moiety, wherein the polyrotaxane has the general formula:

or a salt thereof,
wherein:
n is an integer from 1 to 30;
C and C′ are the same or different and represent endcapping groups of the formula:

wherein:
L 1 is a (C 1 -C 6 )hydrocarbylene group,
G 1 and G 2 , together, form a radical having the formula:

wherein each L 2 is independently a bond or acyl; each G 3 is a substituted or unsubstituted (C 6 -C 50 )hydrocarbyl group, interrupted by 0 to 5 groups chosen from —O—, —NH—, and —S—, wherein the (C 6 -C 50 )hydrocarbyl group; and each s is independently an integer from 1 to 5; and
t is an integer from 2 to 5;
B is a polyalkylene oxide polymer; and
A is a cyclodextrin.

2. The polyrotaxane of claim 1 , wherein the nuclide chelating moiety is a radical of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).

3. The polyrotaxane of claim 1 , further comprising at least one of a radionuclide and a paramagnetic nuclide chelated by the nuclide chelating moiety.

4. The polyrotaxane of claim 3 , wherein the paramagnetic nuclide comprises Gd 3+ .

5. The polyrotaxane of claim 1 , wherein G 3 is a substituted or unsubstituted —O—(C 6 -C 50 )alkyl group or a substituted or unsubstituted (C 6 -C 12 )aryl group, wherein the (C 6 -C 50 )alkyl group and the (C 6 -C 12 )aryl group.

6. The polyrotaxane of claim 1 , wherein G 3 is a cholesteryl group or a 2,4,6-trinitro phenyl group.

7. The polyrotaxane of claim 1 , wherein n is an integer from 5 to 15.

8. The polyrotaxane of claim 1 , wherein n is an integer from 3 to 11.

9. The polyrotaxane of claim 1 , having the structure:

wherein:

10. A pharmaceutical composition comprising the polyrotaxane of claim 1 and a pharmaceutically acceptable carrier.

Assignees

• Purdue Research Foundation

Inventors

• Thompson David H
• Kulkarni Aditya
• Collins Christopher
• Mondjinou Yawo

Classifications

• A61P3/06

  Antihyperlipidemics · CPC title

• G01N33/6893

  related to diseases not provided for elsewhere · CPC title

• A61K51/065

  conjugates with carriers being macromolecules · CPC title

• A61K31/765

  Polymers containing oxygen · CPC title

• A61K31/724

  Cyclodextrins · CPC title