IP Library Granted Patent US 9,089,573
Granted Patent B2
US 9,089,573 · App. 13/386,462 · Granted Jul 28, 2015

Methods and compositions to reduce oxidative stress

Inventor: Louis M. Messina (Westborough, MA)
Assignee: University of Massachusetts
A61K31/519A61K31/198A61K31/375A61K45/06A61K48/005A61K31/495A61K35/13C12N2799/022C12P13/10
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Quick Facts
Patent No.
US 9,089,573
App. No.
13/386,462
Granted
Jul 28, 2015
Kind
B2
Abstract

The invention relates to therapeutic applications for compositions that reduce the level of oxidative stress on cells in vivo or in vitro. The invention describes methods for improving the therapeutic properties of stem cells. The invention also provides combination therapies that are useful to balance the oxidative microenvironment of cells in vivo or in vitro.

Claims (49)

1. A pharmaceutical composition, wherein the active ingredients of the composition consist of:

a. L-arginine,

b. tetrahydrobiopterin, sepiapterin, or dihydrobiopterin, or any combination thereof, and

c. ascorbic acid or ascorbate;

wherein the ratio of (a):(b) is 1-30:1; and

wherein the ratio of (b):(c) is 1:0.1-15.

2. The composition of claim 1 , wherein the active ingredients consist of:

a. L-arginine;

b. tetrahydrobiopterin; and

c. ascorbic acid or ascorbate.

3. The composition of claim 1 , further comprising a pharmaceutically acceptable carrier.

4. A pharmaceutical kit comprising one or more containers housing a pharmaceutical composition formulated as tablets, capsules, powders, granules, or solutions for oral ingestion, wherein the active ingredients of the composition consist of:

a. L-arginine,

b. tetrahydrobiopterin, sepiapterin, or dihydrobiopterin, or any combination thereof, and

c. ascorbic acid or ascorbate;

wherein the ratio of (a):(b) is 1-30:1; and

wherein the ratio of (b):(c) is 1:0.1-15.

5. The kit of claim 4 , wherein at least one container houses a flavoring agent.

6. The kit of claim 4 , wherein each container houses L-arginine; tetrahydrobiopterin; and ascorbic acid or ascorbate; and a pharmaceutically acceptable carrier.

7. The kit of claim 4 , wherein each container houses:

88.5 mg/kg/day L-arginine;

10 mg/kg/day tetrahydrobiopterin;

88.5 mg/kg/day ascorbic acid or ascorbate; and

a pharmaceutically acceptable carrier.

8. A pharmaceutical kit comprising one or more containers housing a pharmaceutical composition formulated as tablets, capsules, powders, granules, or solutions for oral ingestion, wherein the composition consists of:

a. L-arginine;

b. tetrahydrobiopterin, sepiapterin, dihydrobiopterin, or any combination thereof; and

c. ascorbic acid or ascorbate; and

a pharmaceutically acceptable carrier, wherein in each container:

the ratio of (a):(b) is 1-30:1; and

the ratio of (b):(c) is 1:0.1-15.

9. A pharmaceutical composition, wherein the active ingredients of the composition consist of:

a. L-arginine,

b. tetrahydrobiopterin, sepiapterin, or dihydrobiopterin, or any combination thereof, and

c. ascorbic acid or ascorbate;

wherein the ratio of (a):(b) is 1-30:1, and the ratio of (b):(c) is 1:0.1-15; and one or more excipients selected from the group consisting of: hydroxypropyl methylcellulose; sodium carboxymethyl cellulose; or polyvinylpyrrolidine.

10. A pharmaceutical composition consisting of:

a. L-arginine;

b. tetrahydrobiopterin, sepiapterin, dihydrobiopterin, or any combination thereof; and

c. ascorbic acid or ascorbate, and

one or more excipients selected from the group consisting of: hydroxypropyl methylcellulose; sodium carboxymethyl cellulose; or polyvinylpyrrolidine.

11. A pharmaceutical kit comprising one or more containers housing a pharmaceutical composition formulated as tablets, capsules, powders, granules, or solutions for oral ingestion, wherein the active ingredients of the composition consist of:

a. L-arginine;

b. tetrahydrobiopterin, sepiapterin, dihydrobiopterin, or any combination thereof; and

c. ascorbic acid or ascorbate;

wherein each container houses one or more excipients selected from the group consisting of:

hydroxypropyl methylcellulose; sodium carboxymethyl cellulose; or polyvinylpyrrolidine.

12. The kit of claim 11 , wherein the composition is formulated to be mixed with a pharmaceutically acceptable carrier.

13. The kit of claim 11 , wherein the ratio of (a):(b) is 1-30:1, and the ratio of (b):(c) is 1:0.1-15.

Assignments (4)
CONFIRMATORY LICENSE Recorded Oct 30, 2017
From: UNIVERSITY OF MASSACHUSETTS MEDICAL SCH
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 044316/0886 →
CONFIRMATORY LICENSE Recorded Nov 13, 2013
From: UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 031627/0156 →
CONFIRMATORY LICENSE Recorded Jun 7, 2012
From: UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 028333/0317 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 21, 2012
From: MESSINA, LOUIS M.
To: UNIVERSITY OF MASSACHUSETTS
Reel/Frame 027903/0131 →
Continuity (3)
Provisional Application 61227768 · Jul 22, 2009
Provisional Application 61357179 · Jun 22, 2010
Related Publication 20120190731A1 · Jul 26, 2012