Enteric elastomers
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.
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 selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, substituted heteroalkylene, arylene, substituted arylene, heteroarylene, and substituted heteroarylene;
each R 2 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, heteroalkyl, and substituted heteroalkyl;
each R 3 is selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, and 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 selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene;
each R 5 is selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene;
each R 6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, heteroalkyl, and substituted heteroalkyl;
each R 7 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, heteroalkyl, and substituted heteroalkyl;
each R 8 is selected from the group consisting of alkyl and 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 exhibits reversible elongation when stretched from 50% to 1500% of its initial length.
3. 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 as determined by ASTM D575.
4. A polymer composite as in claim 1 , wherein the polymer composite is enteric.
5. 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.
6. A polymer composite as in claim 1 , wherein:
each R 1 is selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene;
each R 2 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
each R 3 is selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene; and
n is an integer between 25 and 250,000.
7. 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 selected from the group consisting of C 4-8 alkylene, substituted C 4-8 alkylene, —(CH 2 CH 2 O) m —, and substituted —(CH 2 CH 2 O) m —;
m is 1, 2, or 3; and
n is an integer between 25 and 250,000.
8. 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.
9. A polymer composite as in claim 1 , wherein:
each R 4 is selected from the group consisting of alkylene and substituted alkylene;
each R 5 is selected from the group consisting of alkylene and substituted alkylene;
each R 6 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
each R 7 is selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
each R 8 is selected the group consisting of alkyl and 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.
10. A polymer composite as in claim 1 , wherein:
or a pharmaceutically acceptable salt thereof, wherein:
each R 6 and R 7 are selected from the group consisting of hydrogen, alkyl, and substituted alkyl;
each R 8 is selected from the group consisting of alkyl and 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.
11. A polymer composite as in claim 1 , wherein the weight ratio of the first polymer to the second polymer is between about 6:1 to about 1:6.
12. A polymer composite as in claim 1 , wherein the first polymer is poly(acryloyl-6-aminocaproic acid) and the second polymer is poly(methacrylic acid-co-ethyl acrylate).
13. A polymer composite as in claim 12 , wherein the poly(methacrylic acid-co-ethyl acrylate) has a molar ratio of methacrylic acid monomer units to ethylacrylate monomer units of about 1:1.
14. A polymer composite as in claim 1 , wherein the polymer composite further has a water content no greater than about 40 wt %.
15. A polymer composite as in claim 1 , wherein the polymer composite comprises an active substance.
16. A gastric residence structure comprising a polymer composite as in claim 1 .
17. An enteric polymer comprising a structure as in Formula (I):
wherein the enteric polymer exhibits reversible elongation when stretched to at least about 50% of its initial length.
18. A method for forming a polymer composite, comprising:
mixing a first polymer comprising a structure as in Formula (I) and a second polymer comprising a structure as in Formula (II):
or pharmaceutically acceptable salts thereof, wherein:
each R 1 is selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, substituted heteroalkylene, arylene, substituted arylene, heteroarylene, and substituted heteroarylene;
each R 2 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, heteroalkyl, and substituted heteroalkyl;
each R 3 is selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene;
each R 4 is selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene;
each R 5 is selected from the group consisting of alkylene, substituted alkylene, heteroalkylene, and substituted heteroalkylene;
each R 6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, heteroalkyl, and substituted heteroalkyl;
each R 7 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, heteroalkyl, and substituted heteroalkyl;
each R 8 is selected from the group consisting of alkyl and substituted alkyl;
n is an integer between 25 and 250,000;
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.
19. A polymer composite as in claim 1 , wherein a functional group attached to a backbone of the first polymer is hydrogen bonded to a functional group attached to the backbone of the second polymer.