Thermally-activated self-immolative materials

Patent metadata

Field	Value
Publication number	US-9580553-B2
Application number	US-201314650221-A
Country	US
Kind code	B2
Filing date	Dec 9, 2013
Priority date	Dec 7, 2012
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

A polymer including a self-immolative polymer segment and a thermally-activated trigger moiety is described. The self-immolative polymer segment includes a head end, a tail end, and a plurality of repeating units. The trigger moiety includes a cycloaddition adduct that is covalently coupled to the head end of the self-immolative polymer segment. When the polymer is exposed to an activation temperature, the cycloaddition adduct undergoes retro-cycloaddition to release the self-immolative polymer segment. The self-immolative polymer segment then decomposes to sequentially release repeating units in a head-to-tail direction.

First claim

What is claimed is:

1. A polymer comprising:
(a) a self-immolative polymer segment comprising a head end, a tail end, and a plurality of repeating units; and
(b) a trigger moiety comprising a cycloaddition adduct, wherein the cycloaddition adduct is covalently coupled to the head end of the self-immolative polymer segment,
wherein the trigger moiety is configured to undergo a retro-cycloaddition reaction at a triggering temperature to cause the self-immolative polymer segment to decompose by releasing repeating units in a sequential head-to-tail direction, and wherein the retro-cycloaddition reaction provides a diene and a carbamoylnitroso moiety.

2. The polymer of claim 1 , wherein the cycloaddition adduct is a [4+2] cycloaddition adduct.

3. The polymer of claim 1 , wherein the trigger moiety comprises an adduct of a diene and a dienophile.

4. The polymer of claim 3 , wherein the diene is selected from the group consisting of anthracene, cyclopentadiene, 1,2,3,4,5-pentamethylcyclopentadiene, 1-hydroxymethyl-1,2,3,4,5-pentamethylcyclopentadiene, 1,3-cyclohexadiene, 1,3-butadiene, safranal, 1-hydroxymethyl-2,6,6-trimethyl-1,3-cyclohexadiene, cycloheptatriene, tropolone, butyltropolone, hinokitiol, butylhinokitiol, eucarvone, eucarveol, purpurogallin, trimethylpurpurogallin, 7-dehydrocholesterol, 3,5-cycloheptadienol, and substituted derivatives thereof.

5. The polymer of claim 3 , wherein the diene is substituted.

6. The polymer of claim 3 , wherein the dienophile comprises a maleimide moiety, acetylene moiety, a carbamoylnitroso moiety, an alkene moiety, or an azo moiety.

7. The polymer of claim 1 , wherein prior to incorporation into the self-immolative polymer segment, the repeating unit comprises an optionally substituted carbamate moiety, optionally substituted carbonate moiety, optionally substituted benzylic ether moiety, or an optionally substituted acetal moiety.

8. The polymer of claim 1 , further comprising a covalently bound therapeutic agent.

9. The polymer of claim 8 , wherein the therapeutic agent is covalently bound to at least one of the repeating units.

10. The polymer of claim 9 , wherein when the repeating unit to which the therapeutic agent is covalently bound to release, the therapeutic agent releases simultaneously with or subsequent to the release of the repeating unit.

11. The polymer of claim 1 , further comprising a water-soluble polymer segment covalently coupled to the self-immolative polymer segment.

12. The polymer of claim 11 , wherein the water-soluble polymer segment comprises poly(ethylene glycol), poly(dimethylacrylamide), poly(vinylpyrrolidone), poly(vinyl alcohol), poly (N-(2-Hydroxypropyl) methacrylamide), poly(divinylether-maleic anhydride), poly(2-alkyl-2-oxazolines), xantham gum, pectin, dextran, or any combination thereof.

13. The polymer of claim 11 , wherein the polymer is water soluble.

14. The polymer of claim 1 , wherein the triggering temperature is from about 37° C. to about 120° C.

15. The polymer of claim 1 , wherein the triggering temperature is at about a physiological temperature.

16. A method for releasing one or more repeating units from a polymer, comprising:
subjecting a polymer according to claim 1 to a temperature sufficient to trigger retro-cycloaddition of the cycloaddition adduct to release the self-immolative polymer segment, wherein the self-immolative polymer segment then decomposes to sequentially release repeating units in a head-to-tail direction.

17. A method for making a patterned structure, comprising:
(a) applying a polymer of claim 1 to a substrate; and
(b) heating the substrate at predetermined locations to a temperature sufficient to effect depolymerization of the polymer to provide a patterned structure.

18. The method of claim 17 , wherein the polymer is applied at the predetermined locations.

19. The method of claim 17 , further comprising (c) applying one or more additional materials to the substrate before step (b).

20. A polymer comprising:
(a) a self-immolative polymer segment comprising a head end, a tail end, and a plurality of repeating units; and
(b) a trigger moiety comprising a cycloaddition adduct, wherein the cycloaddition adduct is covalently coupled to the head end of the self-immolative polymer segment,
wherein the repeating unit is selected from the group consisting of:

 and
substituted derivatives thereof.

21. The polymer of claim 20 , further comprising a covalently bound therapeutic agent.

22. The polymer of claim 21 , wherein the therapeutic agent is covalently bound to at least one of the repeating units.

23. A polymer comprising:
(a) a self-immolative polymer segment comprising a head end, a tail end, and a plurality of repeating units; and
(b) a trigger moiety comprising a cycloaddition adduct, wherein the cycloaddition adduct is covalently coupled to the head end of the self-immolative polymer segment,
wherein the trigger moiety is configured to undergo a retro-cycloaddition reaction at a triggering temperature to cause the self-immolative polymer segment to decompose by releasing repeating units in a sequential head-to-tail direction, and the triggering temperature is at about a physiological temperature.

24. The polymer of claim 23 , further comprising a covalently bound therapeutic agent.

25. The polymer of claim 24 , wherein the therapeutic agent is covalently bound to at least one of the repeating units.

Assignees

• Univ Washington Through Its Center For Commercialization
• Pacific Lutheran Univ

Inventors

• Boydston Andrew J
• Yakelis Neal A
• Berenson Ronald Jay
• Church Derek C
• Peterson Gregory I
• Larsen Michael

Classifications

• C08G81/028 Primary

  containing polyamide sequences · CPC title

• A61K47/48192

  Human Necessities · mapped topic

• C08G85/002

  Post-polymerisation treatment · CPC title

• A61K47/48246

  Human Necessities · mapped topic

• C08G71/04 Primary

  Polyurethanes · CPC title