# US 12,594,304 B2 · Method for treating liver cirrhosis by using composition comprising mesenchymal stem cell. extracellular vesicle produced by mesenchymal stem cell, and growth factor

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- Number: US 12,594,304 B2
- Document ID: US12594304B2
- Status: Granted
- Kind: B2
- Application number: 18/376,545
- Filed: 2023-10-04
- Published: 2024-04-11
- Granted: 2026-04-07
- Earliest claimed: 2022-10-11
- Assignees: Gwo Xi Stem Cell Applied Technology Co., Ltd.
- Applicants: Gwo Xi Stem Cell Applied Technology Co., Ltd.
- Inventors: Po-Cheng Lin; Pi-Chun Huang; Zih-Han Hong; Ming-Hsi Chuang; Yi-Chun Lin; Chia-Hsin Lee; Chun-Hung Chen; Chao-Liang Chang; Kai-Ling Zhang
- Web page: https://patentgrep.com/patent/US12594304B2

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- 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 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- C12N 5/0667: {Adipose-derived stem cells [ADSC]; Adipose stromal stem cells}
- C12N 2500/02: Atmosphere, e.g. low oxygen conditions
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present disclosure provides a method for treating liver cirrhosis by using a composition including mesenchymal stem cells, extracellular vesicles produced by the mesenchymal stem cells, and growth factors. The composition of the present disclosure achieves the effect of treating liver cirrhosis through various efficacy experiments.

## Claims

### Claim 1

A method for treating liver cirrhosis, comprising administering to a subject in need thereof a medicament comprising an effective amount of a composition comprising a mesenchymal stem cell (MSC), an extracellular vesicle (EV) produced by the mesenchymal stem cell, and a growth factor, wherein the growth factor is uteroglobin.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the mesenchymal stem cell is human adipose-derived mesenchymal stem cell (ADSC).

### Claim 3 (depends on 1)

The method according to claim 1, wherein the liver cirrhosis is caused by alcoholic liver disease.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the growth factor is selected from the group consisting of: granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSP), hepatocyte growth factor (HGF), insulin-like growth factor binding proteins-4 (IGFBP-4), insulin-like growth factor binding proteins-6 (IGFBP-6), interleukin-2 (IL-2), platelet-derived growth factor-AB/BB (PDGF-AB/BB), transforming growth factor-a (TGFa), vascular endothelial growth factor (VEGF-A), IL-18 binding protein-a (IL-18BPa), angiopoietin-like 3 (ANGPTL-3), fibroblast growth factor-19 (FGF-19), matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and a combination thereof.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the growth factor is IL-2, PDGF-AB/BB or TGFa, and expressions of the IL-2, PDGF-AB/BB and the TGFa are downregulated.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the mesenchymal stem cell has an effective concentration of liver injection of 7×107-1×108 mesenchymal stem cells.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the composition increases expressions of interleukin-10 (IL-10) and interferon gamma (INF-γ).

### Claim 8 (depends on 1)

The method according to claim 1, wherein the composition reduces levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

### Claim 9 (depends on 1)

The method according to claim 1, wherein the composition has ability to repair liver damage and improves regeneration ability of damaged liver.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the composition enhances synthesis ability of albumin, metabolism ability of bilirubin, synthesis ability of prothrombin, and synthesis and metabolism ability of liver.

### Claim 11 (depends on 2)

The method according to claim 2, wherein the human ADSC is expanded by using the keratinocyte serum-free medium (SFM) supplemented with 1-100 mM N-acetyl-L-cysteine and 0.05-50 mM L-ascorbic acid 2-phosphate.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the human ADSC is further expanded in a culture flask made of a material with an oxygen-containing functional group at ratio of 20-35%.

### Claim 13 (depends on 1)

The method according to claim 1, wherein therapeutic effect of the liver cirrhosis lasts for at least 6 months.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the medicament is in a dosage form for parenteral administration.

### Claim 15

A medicament for treating liver cirrhosis, comprising a mesenchymal stem cell (MSC), an extracellular vesicle (EV) produced by the mesenchymal stem cell, and a growth factor, wherein the growth factor is uteroglobin.