Biodegradable thermo-responsive polymers and uses thereof

Patent metadata

Field	Value
Publication number	US-2018133333-A1
Application number	US-201515532405-A
Country	US
Kind code	A1
Filing date	Dec 3, 2015
Priority date	Dec 4, 2014
Publication date	May 17, 2018
Grant date	—

Abstract

The invention provides for novel thermo-responsive polymers and compositions comprising the same. In some embodiments, the polymers are water soluble, pH-degradable and have tunable lower critical solution temperatures. Other aspects of the invention include micelles and gels comprising the thermo-responsive polymers and derivatives thereof, as well as methods of delivering therapeutic agents comprising administering a biodegradable gel or micelle comprising a polyacetal compound cross-linked with a linker.

First claim

1 . A compound of formula (I)

wherein,
V is

each D may be the same or different and is

or a therapeutic agent core;
each n 1 may be the same or different and is an integer between 2 and 10;
each m 1 may be the same or different and is an integer between 0 and 20;
each X may be the same or different and is C 2 -C 10 alkyl;
each m 2 may be the same or different and is an integer between 0 and 20; and
p is an integer between 3 and 200.

2 . The compound of claim 1 , wherein
each D may be the same or different and is

3 . The compound of claim 0 , wherein
D is

n 1 is an integer between 2 and 10;
m 1 is an integer between 0 and 20;
X is C 2 -C 10 alkyl; and
m 2 is an integer between 0 and 20.

4 . The compound of claim 1 , wherein the value of [(m 1 +m 2 )/p] is a number between 0 and 8.

5 . The compound of claim 1 , wherein the compound has a lower critical solution temperature of about 6° C. to about 80° C.

6 . The compound of claim 5 , wherein the lower critical solution temperature is about 25° C. to about 45° C.

7 - 9 . (canceled)

10 . The compound of claim 1 , wherein X is C 2 -C 5 n-alkyl.

11 . The compound of claim 1 , wherein p is an integer between 3 and 50.

12 - 20 . (canceled)

21 . The compound of claim 1 , wherein each D may be the same or different and is

or a therapeutic agent core.

22 - 25 . (canceled)

26 . The compound of claim 21 , wherein
each n 1 may be the same or different and is an integer between 2 and 4; each m 1 may be the same or different and is an integer between 0 and 2; each X may be the same or different and is C 2 -C 5 alkyl; each m 2 may be the same or different and is an integer between 0 and 3; and p is an integer between 3 and 100,

27 - 29 . (canceled)

30 . The compound of claim 1 wherein the therapeutic agent core is

31 - 85 . (canceled)

86 . A method for treating cancer in a subject the method comprising administering to a subject a therapeutic amount of the compound of claim 1 , wherein the cancer comprises breast cancer, non-small cell lung cancer, pancreatic cancer, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), gastric cancer, Hodgkin lymphoma, neumblastoma, non-Hodgkin lymphoma, ovarian cancer, small cell lung cancer, soft tissue and bone sarcomas, thyroid cancer, transitional cell bladder cancer, Wilms tumor, adjuvant therapy for breast cancer that has spread to the lymph nodes after surgery, renal cell carcinoma, subependymal giant cell astrocytoma, multiple myeloma, T-cell acute lymphoblastic leukemia, T-cell lymphoblastic lymphoma, myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), penile cancer, squamous cell carcinoma of the cervix, of the head and neck, and of the vulva, testicular cancer, mantle cell lymphoma, colorectal cancer, gastric cancer, esophageal cancer, chronic myelogenous leukemia, meningeal leukemia, myelodysplastic syndromes (MDS), adenocarcinoma, prostate cancer, squamous cell carcinoma of the head and neck, Chronic lymphocytic leukemia, cervical cancer, gastroenteropancreatic neuroendocrine tumors, AIDS related Kaposi sarcoma, bladder cancer, melanoma, esophageal cancer, mycosis fungoides, thymoma, thymic carcinoma, choriocarcinoma, Kaposi sarcoma, mycosis fungoides, acute leukemia, and rhabdomyosarcoma.

87 . A chemical composition comprising the compound of claim 1 , wherein
each D may be the same or different and is

or a therapeutic agent core; and water or a liquid chemical carrier.

88 . A method for delivering a therapeutic agent to crops, plants or seeds, the method comprising administering to crops, plants, or seeds the compound of claim 1 .

89 . A compound of formula (III)

wherein,
A is

F is

or a polymer;

Z is a polymer, aryl, hetero-aryl, or vinyl;
V is

each D may be the same or different and is

each n 1 may be the same or different and is an integer between 2 and 10;
each m 1 may be the same or different and is an integer between 0 and 20;
each X may be the same or different and is C 2 -C 10 alkyl;
each m 2 may be the same or different and is an integer between 0 and 20;
n 1 is an integer between 2 and 10;
p is an integer between 3 and 200;
q is an integer between 1 and 100;
s is an integer between 1 and 10;
t is an integer between 1 and 10;
u is an integer between 1 and 100;
G is a polymer, aryl, or alkyl;
R 1 is H or CH 3 ; and
R 2 is H or CH 3 .

90 . The compound of claim 89 , wherein
D is

n 1 is an integer between 2 and 10;
m 1 is an integer between 0 and 20;
X is C 2 -C 10 alkyl;
m 2 is an integer between 0 and 20; and
p is an integer between 3 and 200.

91 . The compound of claim 89 , wherein the value of [(m 1 +m 2 )/p] is a number between 0 and 8.

92 . The compound, of claim 89 , wherein
each n 1 may be the same or different and is an integer between 2 and 4; each m 1 may be the same or different and is an integer between 0 and 2; each X may be the same or different and is C 2 -C 5 alkyl; each m 2 may be the same or different and is an integer between 0 and 3; and p is an integer between 3 and 100.

93 . The compound of claim 89 , wherein X is C 2 -C 5 n-alkyl.

94 . The compound of claim 89 , wherein p is an integer between 3 and 50.

95 . The compound of claim 89 , wherein
A is

F is

Assignees

• Univ Columbia
• Tht Trustees Of Columbia Univ In The City Of New York

Inventors

• Koberstein Jeffrey T
• Samanta Sanjoy
• De Silva Chathuranga

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C08G81/00

  Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers (involving only carbon-to-carbon unsaturated bond reactions C08F299/00 {; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42}) · CPC title

• A61K47/59

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• A61K9/06

  Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)} · CPC title

• A61K47/6907

  the form being a microemulsion, nanoemulsion or micelle · CPC title