Collagen-based therapeutic delivery systems

Patent metadata

Field	Value
Publication number	US-10314940-B2
Application number	US-201515505046-A
Country	US
Kind code	B2
Filing date	Aug 27, 2015
Priority date	Aug 27, 2014
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

A collagen-based therapeutic delivery device includes an insoluble synthetic collagen-fibril matrix comprising a polymerization product of soluble oligomeric collagen or a polymerization product of a mixture of soluble oligomeric collagen with one or more type of non-oligomeric soluble collagen molecules, such as, for example, soluble telocollagen and/or soluble atelocollagen, and an active agent dispersed throughout the collagen-fibril matrix or within a portion of the collagen-fibril matrix. A pre-matrix composition includes an aqueous solution including soluble collagen-fibril building blocks and an active agent in the aqueous solution. The soluble collagen-fibril building blocks include soluble oligomeric collagen or a mixture of soluble oligomeric collagen with non-oligomeric soluble collagen molecules. The building blocks are operable to self-assemble into a macromolecular synthetic collagen-fibril matrix in the absence of an exogenous cross-linking agent. Methods of making and using the pre-matrix composition and the device are also provided.

First claim

What is claimed is:

1. A collagen-based therapeutic delivery device, comprising:
a controlled release collagen-based therapeutic delivery device, the device including:
an insoluble synthetic collagen-fibril matrix comprising a polymerization product of soluble oligomeric collagen or a polymerization product of a mixture of soluble oligomeric collagen with one or more types of non-oligomeric soluble collagen molecules; and
a first active agent dispersed throughout the collagen-fibril matrix or within a portion of the collagen-fibril matrix;
wherein the first active agent is present in a biologically active amount;

wherein the collagen-fibril matrix exhibits a stiffness of at least 5 Pa; and
wherein the microstructure of the collagen-fibril matrix controls the release kinetics of the first active agent in the collagen-based therapeutic delivery device, and wherein the device does not include cells.

2. The therapeutic delivery device of claim 1 , wherein the collagen-fibril matrix comprises type I collagen.

3. The therapeutic delivery device of claim 1 , wherein the collagen-based therapeutic delivery device is a tissue graft.

4. The therapeutic delivery device of claim 1 , wherein the collagen-based therapeutic delivery device is lyophilized.

5. The therapeutic delivery device of claim 1 , wherein the collagen-fibril matrix comprises a polymerization product of a mixture of more than 0 but less than 100 percent soluble oligomeric collagen with more than 0 but less than 100 percent of one or more types of non-oligomeric soluble collagen molecules.

6. The therapeutic delivery device of claim 5 , wherein the collagen-fibril matrix comprises a polymerization product of a mixture of soluble oligomeric collagen with one or more types of non-oligomeric soluble collagen molecules and wherein the oligomeric collagen and non-oligomeric soluble collagen molecules are in a ratio within a range selected from the group consisting of 5:95 to 10:90, 10:90 to 15:85, 15:85 to 20:80, 20:80to 25:75, 25:75 to 50:50, and 50:50 to 75:25.

7. The therapeutic delivery device of claim 1 , further comprising a second active agent dispersed throughout the collagen-fibril matrix or within a portion of the collagen-fibril matrix.

8. The therapeutic delivery device of claim 7 , wherein each of the first and second active agents is a growth factor or a drug.

9. The therapeutic delivery device of claim 1 , wherein the collagen-fibril matrix includes a first portion having a first fibril density and a second portion having a second fibril density; wherein the first fibril density is different than the second fibril density.

10. The therapeutic delivery device of claim 1 , wherein the collagen-fibril matrix includes a first portion having dispersed therein the first active agent and a second portion having dispersed therein a second active agent, wherein the therapeutic delivery device exhibits a first release profile for the first active agent and a second release profile for the second active agent, and wherein the first release profile is different than the second release profile.

11. The therapeutic delivery device of claim 1 , wherein the first active is present in in a biologically active amount sufficient to act as a chemotherapeutic agent, an oncostate, a hemapoietic modulator, an immune modulator, or an osteoinductant.

12. The therapeutic delivery device of claim 1 , wherein the collagen-fibril matrix includes a first portion having a first fibril microstructure and a second portion having a second fibril microstructure.

13. The therapeutic delivery device of claim 1 , wherein the polymerization product includes at least one of telocollagen and atelocollagen.

Assignees

• Purdue Research Foundation Office Of Tech Commercialization
• Purdue Research Foundation

Inventors

• Voytik-Harbin Sherry

Classifications

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61L2300/414

  Growth factors · CPC title

• A61K38/18

  Growth factors; Growth regulators · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · 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