US2020354480A1PendingUtilityA1
Water soluble nitric oxide-releasing polyglucosamines and uses thereof
Assignee: UNIV NORTH CAROLINA CHAPEL HILLPriority: Aug 17, 2012Filed: Jul 23, 2020Published: Nov 12, 2020
Est. expiryAug 17, 2032(~6.1 yrs left)· nominal 20-yr term from priority
C08B 37/003A61P 9/10A61P 43/00C08L 5/08A61P 37/06A61P 35/00A61P 9/00C08B 37/00A61P 15/00A61P 17/02A61P 7/02A61P 31/00A61P 29/00A61K 31/722A61P 1/04A61K 47/60A61K 31/7028A61P 15/10C07H 15/12A61P 25/04A61P 11/00
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Claims
Abstract
The presently disclosed subject matter provides nitric oxide-releasing polysaccharides and oligosaccharides, in particular, polyglucosamines, and their use in biomedical and pharmaceutical applications. More particularly, in some embodiments, the presently disclosed subject matter provides nitric oxide-releasing polysaccharides and oligosaccharides that release nitric oxide in a controlled and targeted manner, thereby prolonging the therapeutic effects of nitric oxide and improving the specificity of nitric oxide delivery to targeted cells and/or tissues.
Claims
exact text as granted — not AI-modifiedThat which is claimed is:
1 . A polyglucosamine comprising,
at least one structural unit:
and optionally, at least one structural unit:
wherein,
R 1 , R 2 , R 3 and R 4 , if present, are each independently selected from the group consisting of hydrogen, C 1-5 alkyl(C═O)— and C 1-5 alkyl;
in each instance, is a single or double bond,
wherein in each instance where it is a double bond, R 1 , R 2 , R 3 or R 4 attached to the double bond-O is absent; when R 1 is absent, R 5 is hydrogen, hydroxyl, C 1-5 alkyl or C 1-5 alkoxy; when R 3 is absent, R 6 is hydrogen, hydroxyl, C 1-5 alkyl or C 1-5 alkoxy;
wherein in each instance where it is a single bond, R 1 , R 2 , R 3 or R 4 attached to the double bond-O is present; when R 1 is present, R 5 is hydrogen;
when R 3 is present, R 6 is hydrogen;
Q is —(CR c R d ) v —;
wherein R c and R d are independently hydrogen or C 1-5 alkyl; and v is an integer from 2 to 6;
p is an integer from 1 to 10;
A is
wherein, L is S, O or N; and
G, in each instance, is independently, hydrogen, or is taken together with L to form a nitric oxide donor or is absent;
X is hydrogen, C 1-5 alkyl or is taken together with N to form a nitric oxide donor;
B is one hydrogen or —Y—Z, wherein Y is a spacer and Z is a polymer or a terminus;
D is NR a R b , wherein R a and R b are independently selected from the group consisting of hydrogen, formyl, C 1-5 alkyl(C═O)—, C 1-5 alkyl and C 1-5 alkyl ester;
or D is
2 . The polyglucosamine of claim 1 , wherein at least one of said X and G is taken together with the atom on the polyglucosamine to which it is bound to form a nitric oxide donor.
3 . The polyglucosamine of claim 1 , comprising the structural unit:
wherein,
m is an integer from 1 to 10,000.
4 . The polyglucosamine of claim 1 , wherein said nitric oxide donor is taken together with the atom on the polyglucosamine to which it is bound is selected from the group consisting of a diazeniumdiolate, nitrosothiol, a nitrosamine, a hydroxyl nitrosamine, a hydroxyl amine, a hydroxyurea, and combination thereof.
5 . The polyglucosamine of claim 4 , wherein said nitric oxide donor is diazeniumdiolate.
6 . The polyglucosamine of claim 3 , wherein m is an integer from 1 to 50.
7 . The polyglucosamine of claim 3 , wherein m is an integer from 1 to 10.
8 . The polyglucosamine of claim 1 , comprising at least one structural unit:
wherein,
D is —NR a R b , wherein R a and R b are independently selected from the group consisting of hydrogen, formyl, C 1-5 alkyl(C═O)—, C 1-5 alkyl and C 1-5 alkyl ester.
9 . The polyglucosamine of claim 8 , wherein
, in each instance, is a single bond R 1 , R 2 , R 3 and R 4 , are each hydrogen, and R 5 and R 6 are each hydrogen.
10 . The polyglucosamine of claim 9 , comprising at least one structural unit:
11 . The polyglucosamine of claim 10 , wherein B is hydrogen.
12 . The polyglucosamine of claim 11 , wherein B is —Y—Z.
13 . The polyglucosamine of claim 12 , wherein B is —Y—Z, wherein Z has the structure:
wherein j, in each instance, is an integer from 1 to 100.
14 . The polyglucosamine of claim 12 , wherein Y has the structure:
wherein,
R p , R q , R s and R t , in each instance, are independently, hydrogen or hydroxyl; and
k is an integer from 1 to 20.
15 . The polyglucosamine of claim 1 , comprising the structural unit:
wherein,
D is
16 . The polyglucosamine of claim 15 , wherein
, in each instance, is a single bond, and R 1 , R 2 , R 3 and R 4 , are each hydrogen.
17 . The polyglucosamine of claim 1 , wherein
B is —Y—Z, wherein Z has the structure:
wherein j, in each instance, is an integer from 1 to 100.
18 . The polyglucosamine of claim 17 , wherein j is an integer from 1 to 50.
19 . The polyglucosamine of claim 17 , wherein j is an integer from 1 to 15.
20 . The polyglucosamine of claim 1 , wherein
A is
wherein G is hydrogen, or is taken together with N to form a nitric oxide donor or is absent; and
B is hydrogen.
21 . The polyglucosamine of claim 1 , comprising the structural unit:
wherein,
m is an integer from 1 to 1,000, and
n is an integer from 1 to 1,000.
22 . The polyglucosamine of claim 21 , wherein m and n are each independently selected from an integer of 1 to 50.
23 . The polyglucosamine of claim 21 , comprising the structural unit:
24 . The polyglucosamine of claim 20 , wherein
X is hydrogen or is taken together with N to form a diazeniumdiolate; and A is
wherein G is hydrogen or is taken together with N to form a diazeniumdiolate.
25 . The polyglucosamine of claim 21 , wherein
B is —Y—Z, wherein Z has the structure:
wherein j, in each instance, is an integer from 1 to 100.
26 . The polyglucosamine of claim 22 , wherein Y has the structure:
wherein,
R p , R q , R s and R t , in each instance, are independently, hydrogen or hydroxyl; and
k is an integer from 1 to 20.
27 . The polyglucosamine of claim 1 , wherein A is N.
28 . The polyglucosamine of claim 1 , wherein A is S.
29 . The polyglucosamine of claim 1 , wherein
R c and R d are independently hydrogen or methyl; and v is 2.
30 . A method of delivering nitric oxide to a subject, comprising:
administering an effective amount of said polyglucosamine of claim 1 to said subject.
31 . A method of treating a disease state, comprising:
administering an effective amount of said polyglucosamine of claim 1 to a subject in need thereof, wherein said disease state is selected from the group consisting of a cancer, a cardiovascular disease, a microbial infection; platelet aggregation and platelet adhesion caused by the exposure of blood to a medical device; pathological conditions resulting from abnormal cell proliferation; transplantation rejections, autoimmune diseases, inflammation, vascular diseases; scar tissue; wound contraction, restenosis, pain, fever, gastrointestinal disorders, respiratory disorders, sexual dysfunctions, and sexually transmitted diseases.
32 . The method of claim 31 , wherein said disease state is cystic fibrosis.
33 . A pharmaceutical formulation comprising:
iii. said polyglucosamine of claim 1 ; and iv. a pharmaceutically acceptable carrier.
34 . The pharmaceutical formulation of claim 33 , wherein said polyglucosamine is water-soluble.
35 . The polyglucosamine of claim 1 , wherein said polyglucosamine is water soluble.Join the waitlist — get patent alerts
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