Enteric elastomers

Patent metadata

Field	Value
Publication number	US-11083690-B2
Application number	US-201916528197-A
Country	US
Kind code	B2
Filing date	Jul 31, 2019
Priority date	Jun 11, 2014
Publication date	Aug 10, 2021
Grant date	Aug 10, 2021

Abstract

Enteric elastomers and related methods are generally provided. In some embodiments, the enteric elastomer is a polymer composite. Certain embodiments comprise a polymer composite in which hydrogen bonds within two carboxyl group-containing polymers cross-link the polymer networks into an elastic and pH-responsive polymer composite. Advantageously, this polymer composite has the capacity of being stable and elastic in an acidic environment such as that of the stomach but can be dissolved in a neutral pH environment such as that of the small and large intestines. In some embodiments, the polymer composites described herein comprise a mixture of two or more polymers with carboxyl functionality such that the two or more polymers form hydrogen bonds. In certain embodiments, the polymer composite has both enteric and elastic properties.

First claim

What is claimed is:

1. A polymer composite, comprising:
a first polymer comprising a structure as in Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
each R 1 is the same or different and is selected from the group consisting of optionally substituted alkylene, optionally substituted heteroalkylene, optionally substituted arylene, and optionally substituted heteroarylene;
each R 2 is the same or different and is selected from the group consisting of hydrogen, optionally substituted alkyl, and optionally substituted heteroalkyl;
each R 3 is the same or different and is selected from the group consisting of optionally substituted alkylene and optionally substituted heteroalkylene;
n is an integer between 25 and 250,000; and
a second polymer comprising a structure as in Formula (II) hydrogen bonded to the first polymer:

or a pharmaceutically acceptable salt thereof, wherein:
each R 4 is the same or different and is selected from the group consisting of optionally substituted alkylene and optionally substituted heteroalkylene;
each R 5 is the same or different and is selected from the group consisting of optionally substituted alkylene and optionally substituted heteroalkylene;
each R 6 is the same or different and is selected from the group consisting of hydrogen, optionally substituted alkyl, and optionally substituted heteroalkyl;
each R 7 is the same or different and is selected from the group consisting of hydrogen, optionally substituted alkyl, and optionally substituted heteroalkyl;
each R 8 is the same or different and is optionally substituted alkyl;
p is an integer between 1 and 10;
q is an integer between 1 and 10; and
z is an integer between 1 and 150,000, provided that (p+q)*z is greater than or equal to 20.

2. A polymer composite as in claim 1 , wherein the polymer composite is elastic.

3. A polymer composite as in claim 1 , wherein the polymer composite may be configured for undergoing at least about 45 degrees, at least about 60 degrees, at least about 90 degrees, at least about 120 degrees, at least about 150 degrees, or at least about 180 degrees of mechanical bending deformation without breaking.

4. A polymer composite as in claim 1 , wherein the polymer composite has a strength of recoil sufficient to substantially return the polymer composite to its pre-deformed shape in less than about 30 minutes, in less than about 10 minutes, in less than about 5 minutes, or in less than about 1 minute after release of the mechanical deformation.

5. A polymer composite as in claim 1 , wherein the polymer composite exhibits reversible elongation when stretched from 50% to 1500% of its initial length.

6. A polymer composite as in claim 1 , where the polymer composite has an elastic modulus ranging between about 0.1 MPa and about 100 MPa.

7. A polymer composite as in claim 1 , wherein the polymer composite is enteric.

8. A polymer composite as in claim 1 , wherein the polymer composite is stable at a pH less than about 5 and dissolves at a pH greater than about 5.5.

9. A polymer composite as in claim 1 , wherein:
each R 1 is the same or different and is selected from the group consisting of optionally substituted alkylene and optionally substituted heteroalkylene;
each R 2 is the same or different and is selected from the group consisting of hydrogen and optionally substituted alkyl;
each R 3 is the same or different and is selected from the group consisting of optionally substituted alkylene and optionally substituted heteroalkylene; and
n is an integer between 25 and 250,000.

10. A polymer composite as in claim 1 , wherein:
each R 1 is the same or different and is —[C(R′ 2 )] g —;
each R 2 is the same or different and is selected from the group consisting of hydrogen and optionally substituted alkyl;
each R 3 is the same or different and is selected from the group consisting of optionally substituted C 2-10 alkylene and optionally substituted hetero C 2-8 alkylene;
each R′ is the same or different and is selected from the group consisting of hydrogen and optionally substituted alkyl;
g is 1, 2, 3, 4, or 5; and
n is an integer between 25 and 250,000.

11. A polymer composite as in claim 1 , wherein:
each R 1 is the same or different and is —[C(R′ 2 )] g —;
each R 2 is the same or different and is selected from the group consisting of hydrogen and optionally substituted alkyl;
each R 3 is the same or different and is selected from the group consisting of optionally substituted C 4-8 alkylene and —(CH 2 CH 2 O) m —;
each R′ is the same or different and is selected from the group consisting of hydrogen and optionally substituted alkyl;
g is 1, 2, 3, 4, or 5;
m is 1, 2, or 3; and
n is an integer between 25 and 250,000.

12. A polymer composite as in claim 1 , wherein the first polymer comprises a structure as in:

or a pharmaceutically acceptable salt thereof, wherein:
R 3 is the same or different and is selected from the group consisting of optionally substituted C 4-8 alkylene and —(CH 2 CH 2 O) m —;
m is 1, 2, or 3; and
n is an integer between 25 and 250,000.

13. A polymer composite as in claim 1 , wherein the first polymer comprises a structure as in:

or a pharmaceutically acceptable salt thereof, wherein n is an integer between 25 and 250,000.

14. A polymer composite as in claim 1 , wherein the first polymer is selected from the group consisting of a polymer of an acryloylaminoalkylene acid monomer, or salts thereof.

15. A polymer composite as in claim 14 wherein the acryloylaminoalkylene acid monomer is selected from the group consisting of acryloyl-5-aminopentanoic acid, acryloyl-6-aminocaproic acid, acryloyl-7-aminoheptanoic acid, acryloyl-8-aminooctanoic acid, acryloyl-9-aminonoanoic acid, acryloyl-10-aminodecanoic acid, acryloyl-11-aminoundecanoic acid, acryloyl-12-aminododecanoic acid, methacryloyl-5-aminopentanoic acid, methacryloyl-6-aminocaproic acid, methacryloyl-7-aminoheptanoic acid, methacryloyl-8-aminooctanoic acid, methacryloyl-9-aminonoanoic acid, methacryloyl-10-aminodecanoic acid, methacryloyl-11-aminoundecanoic acid, methacryloyl-12-aminododecanoic acid, salts thereof, and combinations thereof.

16. A polymer composite as in claim 1 , wherein the first polymer is a homopolymer of acryloyl-6-aminocaproic acid or salts thereof.

17. A polymer composite as in claim 1 , wherein:
each R 4 is the same or different and is optionally substituted alkylene;
each R 5 is the same or different and is optionally substituted alkylene;
each R 6 is the same or different and is selected from the group consisting of hydrogen and optionally substituted alkyl;
each R 7 is the same or different and is selected from the group consisting of hydrogen and optionally substituted alkyl;
each R 8 is the same or different and is optionally substituted alkyl;
p is an integer between 1 and 10;
q is an integer between 1 and 10; and
z is an integer between 1 and 150,000, provided that (p+q)*z is greater than or equal

Assignees

• Massachusetts Inst Technology
• Brigham & Womens Hospital Inc
• Tokitae Llc

Inventors

• Zhang Shiyi
• Bellinger Andrew
• Traverso Carlo Giovanni
• Langer Robert S
• Glettig Dean Liang
• Wood Jr Lowell L
• Eckhoff Philip A

Classifications

• C08G63/08

  Lactones or lactides · CPC title

• C08G18/73

  acyclic · CPC title

• C08G18/4277

  Caprolactone and/or substituted caprolactone · CPC title

• A61K47/6901

  Conjugates being cells, cell fragments, viruses, ghosts, red blood cells or viral vectors · CPC title

• A61K47/58

  obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin · CPC title