# US 2021/0275577 A1 · Molecular hydrogen-containing composition for regulating intracellular signal transduction

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- Number: US 2021/0275577 A1
- Document ID: US20210275577A1
- Status: Published application
- Kind: A1
- Application number: 17/191,417
- Filed: 2021-03-03
- Published: 2021-09-09
- Earliest claimed: 2020-03-09
- Assignees: Miz Co., Ltd.; Osaka University
- Applicants: MiZ Company Limited; Osaka University
- Inventors: Fumitake SATOH; Bunpei SATO; Shinichi HIRANO; Ryosuke KUROKAWA; Yusuke ICHIKAWA; Hiroshi MATSUURA; Kentaro SHIMIZU; Hiroshi OGURA; Takeshi SHIMAZU
- Web page: https://patentgrep.com/patent/US20210275577A1

## CPC

- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/007: {Pulmonary tract; Aromatherapy}
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 31/04: Antibacterial agents
- C01B 3/02: Production of hydrogen; Production of gaseous mixtures containing hydrogen
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C01B: NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; {METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C}

## Abstract

The present invention provides a composition for regulating intracellular signal transduction. More specifically, the present invention provides a composition for prevention and/or improvement of a symptom associated with intracellular signal transduction in a subject, comprising molecular hydrogen as an active ingredient.

## Claims

### Claim 1

A method for regulating intracellular signal transduction, comprising administering a composition containing an effective amount of molecular hydrogen.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the intracellular signal transduction is glycolysis, gluconeogenesis, and/or carbohydrate metabolism, and/or inflammatory signal transduction in an organ.

### Claim 3 (depends on 2)

The method according to claim 2, wherein a gene related to the gluconeogenesis is one or more genes selected from the group consisting of PFKB1, PGAM2, G6PC, and PCK1.

### Claim 4 (depends on 2)

The method according to claim 2, wherein a gene related to the glycolysis and gluconeogenesis is one or more genes selected from the group consisting of PGAM2, ADH4, G6PC, GCK, and PCK1.

### Claim 5 (depends on 2)

The method according to claim 2, wherein a gene related to the glycolysis and carbohydrate metabolism is one or more genes selected from the group consisting of PDK2, PFKB1, PCDH12, ST6GALNAC6, PGAM2, PTK2B, ADRA1B, ADRB3, C1QTNF, ALDH1A1, ALDH1B1, PRKAG2, KLB, SLC2A2, SLC2A5, PPP1R3C, G6PC, SORD, B4GALT4, GALM, GCGR, GCK, PTH1R, GPD1L, NEU2, DHDH, ANGPTL3, CA5A, GPD1, EPM2A, GNE, PPP1R3B, RBP4, HAGH, and PCK1.

### Claim 6 (depends on 2)

The method according to claim 2, wherein the organ is at least one of liver, lung, and intestine.

### Claim 7 (depends on 2)

The method according to claim 2, wherein a pathway of the inflammatory signal transduction is acute phase response signaling in a liver and/or an intestine, LPS/IL-1 mediated inhibition of RXR function in the liver and/or the intestine, IL-6 signaling in the liver and/or the intestine, STAT3 pathway in the intestine, HMGB1 signaling in the intestine, or interferon signaling in a lung.

### Claim 8 (depends on 7)

The method according to claim 7, wherein a gene related to the inflammatory signal transduction pathway is one or more genes selected from the group consisting of genes coding for Cd14 antigen in the liver, TGF-beta activated kinase 1/MAP3K7 binding protein 1 in the liver, suppressor of cytokine signaling 1 in the liver, interleukin 1 receptor antagonist in the liver, interleukin 6 receptor alpha in the intestine, tumor necrosis factor receptor superfamily member 9 in the intestine, interleukin 1 receptor-like 1 in the intestine, suppressor of cytokine signaling 1 in the intestine, lipopolysaccharide binding protein in the intestine, interleukin 10 in the lung, and suppressor of cytokine Signaling 1 in the lung.

### Claim 9 (depends on 8)

The method according to claim 8, wherein, in a transduction pathway in the liver involving the gene related to the inflammatory signal transduction pathway, a signal is transmitted from IL-2 and/or IL12 outside a cell, via CD11 and/or TLR2 in the plasma membrane of the cell, further via NFkBIA in the cytoplasm, and via NFkB, STAT3, NFkB1, STAT1, STAT4, STAT6, STAT6A, SP1, RCLA, and/or GEBPB in the nucleus of the cell.

### Claim 10 (depends on 8)

The method according to claim 8, wherein, in a transduction pathway in the intestine involving the gene related to the inflammatory signal transduction pathway, a signal is transmitted from IL6, IL1B, TNF, and/or IFN6 outside a cell, via NFkBIA in the cytoplasm, and further via NFkB, STAT3, RELA, JUN, TP53, STAT1, FOS, REL, Ap1, and/or MYC in the nucleus of the cell.

### Claim 11 (depends on 8)

The method according to claim 8, wherein, in a transduction pathway in the lung involving the gene related to the inflammatory signal transduction pathway, a signal is transmitted from IL10, IL15, Ige, TNF, and/or IFNG outside a cell, via STAT5a/b and/or NFkBIA in the cytoplasm, and further via STAT3, NFkB, STAT1, NFkB1, JUN, CEBPB, and/or RELA in the nucleus of the cell.

### Claim 12 (depends on 1)

The method according to claim 1, wherein the composition is a gas composition or a liquid composition.

### Claim 13 (depends on 12)

The method according to claim 12, wherein the gas composition has a hydrogen concentration of higher than zero (0) and not higher than 18.5% by volume.

### Claim 14 (depends on 12)

The method according to claim 12, wherein the liquid composition has a hydrogen concentration of 3 ppm to 10 ppm.

### Claim 15 (depends on 1)

The method according to claim 1, wherein the composition is administered to a mammalian subject.

### Claim 16 (depends on 1)

The method according to claim 1, wherein the composition is administered to a human.

### Claim 17 (depends on 1)

The method according to claim 1, wherein the composition is produced by using a hydrogen gas generating apparatus or a hydrogen water generating apparatus.

### Claim 18 (depends on 1)

The method according to claim 1, wherein a disease controllable by the regulation of intracellular signal transduction is one or more diseases selected from the group consisting of sepsis, inflammatory bowel diseases (ulcerative colitis, Crohn's disease, intestinal Bechet's disease), pneumonia (bacterial pneumonia, viral pneumonia, fungal pneumonia, interstitial pneumonia, allergic pneumonia), COPD, hepatitis (viral hepatitis, alcoholic hepatitis, NAFLD, drug-induced hepatitis, autoimmune hepatitis), diabetes mellitus, and complications of diabetes mellitus.

### Claim 19 (depends on 1)

The method according to claim 1, wherein, based on the intracellular signal transduction in each organ, the intracellular signal transduction is regulated by an administration method selected from the group consisting of inhalation of a hydrogen gas, oral administration of hydrogen water, and drip infusion and/or intraperitoneal administration of hydrogen-containing physiological saline.

### Claim 20 (depends on 18)

A system for deriving a treatment method and/or a treatment strategy for preventing or improving the disease according to claim 18 using a composition comprising an effective amount of molecular hydrogen.
