Epimorphic regeneration and related hydrogel delivery systems

Patent metadata

Field	Value
Publication number	US-9675607-B2
Application number	US-201414544003-A
Country	US
Kind code	B2
Filing date	Nov 13, 2014
Priority date	Nov 13, 2013
Publication date	Jun 13, 2017
Grant date	Jun 13, 2017

Abstract

Methods and compositions are described for enhancing tissue regeneration or wound repair in a mammalian subject comprising a composition comprising (a) a proline hydroxylase inhibitor component or molecule that increases or upregulates HIF1a and (b) a carrier component comprising a hydrogel.

First claim

We claim:

1. A drug delivery system for epimorphic regeneration, said system comprising a first macromonomer component of a formula

a second macromonomer component of a formula

wherein Cys is an N-terminal cysteine residue, each of R 1 and R 2 is independently selected from hexaglycolic and tripentaerythritolic moieties, each of n1 and n2 is an integer independently selected from 1 to about 201; and a drug component for up-regulation of hypoxia inducible factor 1a (H1F1a), said drug component selected from proline hydroxylase inhibitor compounds and prodrugs thereof, a said prodrug comprising a said proline hydroxylase inhibitor compound coupled to a cleavable polymer component, said drug component in an amount to produce a regenerative response.

2. The drug delivery system of claim 1 wherein each said macromonomer component is in a fluid medium.

3. The drug delivery system of claim 2 wherein said first and second macromonomer components are cross-linked to provide a hydrogel, and said drug component is dispersed therein.

4. The drug delivery system of claim 1 wherein a said drug component is selected from 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), a poly(alkylene oxide) coupled prodrug of 1,4-DPCA, dimethyloxallyl glycine (DMOG), 30-amino-3,14,25-trihydroxy-3,9,14,20,25-pentaazatriacontane-2,10,13,21,24-pentone (DFX), 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (Imiquimod) and CoCl 2 .

5. The drug delivery system of claim 4 wherein a said drug component is a poly(alkylene oxide) prodrug of 1,4-DPCA.

6. A drug delivery system for epimorphic regeneration, said system comprising a first macromonomer component of a formula

a second macromonomer component of a formula

wherein Cys is an N-terminal cysteine residue, each of R 1 and R 2 is independently selected from hexaglycolic and tripentaerythritolic moieties, each of n1 and n2 is an integer independently selected from 1 to about 201; and a drug component for up-regulation of hypoxia inducible factor 1a (H1F1a), said drug component selected from proline hydroxylase inhibitor compounds and prodrugs thereof, a said prodrug comprising a said proline hydroxylase inhibitor compound coupled to a cleavable poly(alkene oxide) block copolymer component, said drug component in an amount to provide an H1F1a level for induction of a regenerative response.

7. The drug delivery system of claim 6 wherein said first and second macromonomer components are cross-linked to provide a hydrogel, and said drug component is dispersed therein.

8. The drug delivery system of claim 6 wherein a said drug component is selected from 1,4-DPCA, a poly(alkylene oxide) coupled prodrug of 1,4-DPCA, DMOG, DFX, Imiquimod and CoCl 2 .

Assignees

• Univ Northwestern
• Wistar Inst

Inventors

• Messersmith Phillip B
• Strehin Iossif A
• Heber-Katz Ellen

Classifications

• C08G65/3344

  containing oxygen in addition to sulfur · CPC title

• C08G2210/00

  Compositions for preparing hydrogels · CPC title

• C08G65/332

  containing carboxyl groups, or halides, or esters thereof · CPC title

• C08L2203/02

  for biomedical use · CPC title

• C08G65/3348

  containing nitrogen in addition to sulfur · CPC title