Polythioaminals and Uses Thereof

Patent metadata

Field	Value
Publication number	US-2017049902-A1
Application number	US-201514830251-A
Country	US
Kind code	A1
Filing date	Aug 19, 2015
Priority date	Aug 19, 2015
Publication date	Feb 23, 2017
Grant date	—

Abstract

Polythioaminal polymers are made from hexahydrotriazine precursors and dithiol precursors. The precursors are blended together and subjected to mild heating to make the polymers. The polymers have the general structure

wherein each R 1 is independently an organic or hetero-organic group, each R 2 is independently a substituent having molecular weight no more than about 120 Daltons, X and Z are each a sulfur-bonded species, at least one of X and Z is not hydrogen, and n is an integer greater than or equal to 1. X and Z may be hydrogen or a functional group, such as a thiol-reactive group. The reactive thiol groups of the polythioaminal may be used to attach thiol-reactive end capping species. By using water soluble or water degradable dithiols, such as polyether dithiols, water soluble polythioaminals may be made. Some such polymers may be used to deliver therapeutics with non-toxic aqueous degradation products.

First claim

1 . A polymer having the general structure

wherein each R 1 is independently an organic or hetero-organic species, each R 2 is independently a substituent having a molecular weight no more than about 120 Daltons, X and Z are each a sulfur-bonded species, at least one of X and Z is not hydrogen, and n is an integer greater than or equal to 1.

2 . The polymer of claim 1 , wherein X is a biologically active species.

3 . The polymer of claim 1 , wherein X is a peptide species.

4 . The polymer of claim 3 , wherein each instance of R 1 is a polymer.

5 . The polymer of claim 3 , wherein at least one instance of R 1 is polyethylene glycol.

6 . The polymer of claim 1 , wherein each instance of R 2 is a methyl group.

7 . The polymer of claim 1 , wherein X is selected from the group consisting of hydrogen, an alkane thiol, an aromatic thiol, a peptide, a thio-acid, a nucleotide, and combinations thereof.

8 . The polymer of claim 1 , wherein each instance of R 1 is the same species.

9 . The polymer of claim 1 , wherein the polymer is a random copolymer.

10 . The polymer of claim 1 , wherein X is a species selected from the group consisting of a cargo, a linking group, a medicine, a functional species, a polymerization starter, a chemical species capable of initiating depolymerization, and combinations thereof.

11 . A polymer comprising a repeating unit with the following structure:

and a segment with the following structure:

wherein R 1 is an organic or hetero-organic species, R 2 is a substituent having a molecular weight no more than about 120 Daltons, X is a linking group covalently bonded to a sulfur atom, and K is any radical suitable for bonding to X.

12 . The polymer of claim 11 , wherein X is selected from the group consisting of hexyl, dihydroxybutyl, and polyethylene glycol.

13 . The polymer of claim 12 , comprising a segment with the following structure:

wherein Z is a therapeutic agent.

14 . The polymer of claim 13 , wherein the therapeutic agent is selected from the group consisting of a peptide, a thio-acid, a nucleotide, and combinations thereof.

15 . The polymer of claim 14 , wherein the polymer has a weight-average molecular weight of at least about 10,000 Daltons.

16 . The polymer of claim 11 , comprising a segment with the following structure:

wherein Z is a species selected from the group consisting of an alkane thiol, an aromatic thiol, a peptide, a thio-acid, a nucleotide, and combinations thereof.

17 . The polymer of claim 12 , comprising a segment with the following structure:

wherein Z is a species selected from the group consisting of a cargo, a medicine, a chemical species capable of initiating depolymerization, and combinations thereof.

18 . A method of forming a material, comprising:
mixing an N-substituted hexahydrotriazine with a dithiol to form a first mixture; and heating the first mixture to form a polythioaminal polymer, wherein the substituent bonded to one or more of the nitrogen atoms of the N-substituted hexahydrotriazine forms a hydride that is volatile at temperatures less than 200° C.

19 . The method of claim 18 , comprising adding a thiol-reactive material to the polythioaminal polymer to form a second mixture, and heating the second mixture to form a modified polythioaminal polymer.

20 . The method of claim 19 , wherein the thiol-reactive material comprises a species that is a cargo, a linking group, a medicine, a functional species for further modification after construction of the end-modified polythioaminal polymer, a polymerization starter, a chemical species capable of initiating depolymerization, and combinations thereof.

21 . The method of claim 18 , comprising adding a solvent to the N-substituted hexahydrotriazine prior to mixing with the dithiol.

22 . The method of claim 19 , wherein the modified polythioaminal polymer is a therapeutic agent.

Assignees

• IBM

Inventors

• Hedrick James
• Boday Dylan
• GARCIA Jeannette
• Wojtecki Rudy
• Chin Willy
• Ke Xiyu
• Yang Yi Yan

Classifications

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title

• C08G65/48

  Polymers modified by chemical after-treatment · CPC title

• A61K38/08

  Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61K47/48215 Primary

  Human Necessities · mapped topic

• A61K31/795

  Polymers containing sulfur · CPC title