IP Library Granted Patent US 12,465,584
Granted Patent B2
US 12,465,584 · App. 18/298,825 · Granted Nov 11, 2025

Agent for elevating nitric oxide concentration

Inventors: Masahiko Morita (Tokyo, JP); Ayako Kamimura (Tokyo, JP)
Assignee: KYOWA HAKKO BIO CO., LTD.
A61K31/198A61K38/063
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,465,584
App. No.
18/298,825
Granted
Nov 11, 2025
Kind
B2
Abstract

An agent for elevating nitric oxide (NO) concentration comprising glutathione or a salt thereof as an active ingredient; an agent for elevating NO concentration comprising glutathione or a salt thereof as an active ingredient for preventing or ameliorating a vascular endothelial malfunction-related symptom, or dilating blood vessels or promoting blood flow by elevating NO concentration; and a method for elevating NO concentration by ingesting glutathione or a salt thereof.

Claims (8)

1 . A method for elevating nitric oxide (NO) concentration comprising orally administering glutathione or a salt thereof at a dose of 10 mg to 10 g per day to elevate the NO concentration of a subject who desires improvement in exercise performance,

wherein the glutathione or a salt thereof is orally administered as a tablet, a powder, a granule, a pill, an infusion decoction, a capsule, a drink with glutathione dissolved therein, a drink with a salt of glutathione dissolved therein, a solution, an elixir, an extract, a tincture, or a fluid extract, and

wherein the elevated NO concentration causes exercise performance improvement in the subject.

2 . A method for dilating blood vessels or promoting blood flow in a subject comprising orally administering glutathione or a salt thereof at a total dose of 10 mg to 10 g per day to dilate blood vessels or promote blood flow in a subject who desires improvement in exercise performance,

wherein the glutathione or a salt thereof is orally administered as a tablet, a powder, a granule, a pill, an infusion decoction, a capsule, a drink with glutathione dissolved therein, a drink with a salt of glutathione dissolved therein, a solution, an elixir, an extract, a tincture, or a fluid extract, and

wherein the dilation of the blood vessels or promotion of blood flow causes exercise performance improvement in the subject.

3 . The method for elevating NO concentration according to claim 1 , wherein the glutathione or a salt thereof is reduced glutathione or a salt thereof, or/and oxidized glutathione or a salt thereof.

4 . The method for dilating blood vessels or promoting blood flow in a subject according to claim 2 , wherein the glutathione or a salt thereof is reduced glutathione or a salt thereof, or/and oxidized glutathione or a salt thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 11, 2023
From: MORITA, MASAHIKO; KAMIMURA, AYAKO
To: KYOWA HAKKO BIO CO., LTD.
Reel/Frame 063291/0959 →
Priority Claims (1)
JP 2013-008239 · Jan 21, 2013 · national
Continuity (2)
Division 14762108
Related Publication 20230263761A1 · Aug 24, 2023
References Cited (55)
US 5204114A · Demopoulos et al. · 1993 [cited by applicant]
US 5922345A · Horrobin et al. · 1999 [cited by applicant]
US 6159500A · Demopoulos et al. · 2000 [cited by applicant]
US 6444432B1 · Kleinfeld · 2002 [cited by applicant]
US 10094031B2 · Fukumoto et al. · 2018 [cited by applicant]
US 10640532B2 · Ooshima et al. · 2020 [cited by applicant]
US 10774109B2 · Fukumoto et al. · 2020 [cited by applicant]
US 10858393B2 · Fukumoto et al. · 2020 [cited by applicant]
US 20050192210A1 · Rothbard et al. · 2005 [cited by applicant]
US 20050192229A1 · Perricone · 2005 [cited by applicant]
US 20060099244A1 · Guilford · 2006 [cited by applicant]
US 20060189603A1 · Garvey et al. · 2006 [cited by applicant]
US 20070259024A1 · Furukawa et al. · 2007 [cited by applicant]
US 20100197577A1 · Horiba et al. · 2010 [cited by applicant]
US 20110129523A1 · Guilford et al. · 2011 [cited by applicant]
CN 1408427A · 2003 [cited by applicant]
CN 1748785A · 2006 [cited by applicant]
CN 101027078A · 2007 [cited by applicant]
CN 101703813A · 2010 [cited by applicant]
JP H04074135A · 1992 [cited by applicant]
JP 2001507696A · 2001 [cited by applicant]
JP 2008531579A · 2008 [cited by applicant]
WO WO1997016983A1 · 1997 [cited by applicant]
WO WO2008129851A1 · 2008 [cited by applicant]
WO WO2013122188A1 · 2013 [cited by applicant]
Adachi et al., “Decreased aortic glutathione levels may contribute to impaired nitric oxide-induced relaxation in hypercholesterolaemia,” [cited by applicant]
Atakishi et al., “Effects of Reduced Glutathione on Nitric Oxide Level, Total Antioxidant and Oxidant Capacity and Adenosine Deaminase Activity,” [cited by applicant]
Arjinpathana et al., “Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study,” [cited by applicant]
Aronow et al., “Prevalence of Coexistence of Coronary Artery Disease, Peripheral Arterial Disease, and Atherothrombotic Brain Infarction in Men and Women ≥ 62 Years of Age,” [cited by applicant]
Brass et al., “Acquired skeletal muscle metabolic myopathy in atherosclerotic peripheral arterial disease,” [cited by applicant]
Chanséaume et al., “Potential Mechanisms of Muscle Mitochondrial Dysfunction in Aging and Obesity and Cellular Consequences,” [cited by applicant]
Cheung et al., “Glutathione causes coronary vasodilation via a nitric oxide- and soluble guanylate cyclase-dependent mechanism,” [cited by applicant]
Fujii et al., “Kino Sokyugata Kobo Ekisu no Oyo to Tekai,” [cited by applicant]
Ghigo et al., “Nitric oxide synthesis is impaired in glutathione-depleted human umbilical vein endothelial cells,” [cited by applicant]
Ghigo et al., “Correlation between nitric oxide synthase activity and reduced glutathione level in human and murine endothelial cells,” [cited by applicant]
Haas et al., “Exercise Training and Peripheral Arterial Disease,” [cited by applicant]
Hayashi et al., “l-Citrulline and l-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits,” [cited by applicant]
Henry, “Mechanisms of Changes in Basal Metabolism During Ageing,” [cited by applicant]
Hien et al., “Analysis of Pomelo Value Chain in Ben Tre Province,” [cited by applicant]
Kerksick et al., “The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress,” [cited by applicant]
Martina et al., “Administration of glutathione in patients with type 2 diabetes mellitus increases the platelet constitutive nitric oxide synthase activity and reduces PAI-1,” [cited by applicant]
Misner, “Intravenous Glutathione Enhances Cycling Time Trial Performance (A Case Study),” originally published as “Does Glutathione Enhance Exercise Performance?—A Case Study,” [cited by applicant]
Ochiai et al., “Short-term effects of L-citrulline supplementation on arterial stiffness in middle-aged men,” [cited by applicant]
Prasad et al., “Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability,” [cited by applicant]
Sugimura et al., “Effect of orally administered reduced- and oxidized-glutathione against acetaminophen-induced liver injury in rats,” [cited by applicant]
Vanhatalo et al., “Dietary nitrate reduces muscle metabolic perturbation and improves exercise tolerance in hypoxia,” [cited by applicant]
Zhijun et al., “Effect of Reduced Glutathione on hsCRP and Vascular Endothelial Function of Patients with Essential Hypertension,” [cited by applicant]
Zizola et al., “Metabolic and structural impairment of skeletal muscle in heart failure,” [cited by applicant]
Canadian Intellectual Property Office, Office Action in Canadian Patent Application No. 2,898,416 (Sep. 23, 2019). [cited by applicant]
China National Intellectual Property Administration, Notification of First Office Action in Chinese Patent Application No. 201480005570.8 (Aug. 12, 2016). [cited by applicant]
China National Intellectual Property Administration, The Fourth Office Action in Chinese Patent Application No. 201480005570.8 (Dec. 23, 2021). [cited by applicant]
European Patent Office, Partial Supplementary European Search Report in European Patent Application No. 14740411.5 (Dec. 9, 2016). [cited by applicant]
Japanese Patent Office, International Search Report in International Patent Application No. PCT/JP2014/051102 (Apr. 22, 2014). [cited by applicant]
U.S. Appl. No. 14/762,108, filed Jul. 20, 2015, Pending. [cited by applicant]
Canadian Intellectual Property Office, Office Action in Canadian Application No. 2,898,416 (Jun. 12, 2024). [cited by applicant]