# US 12,178,902 B1 · Methods and compositions for fluid drainage by Piezo ion channel activation

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- Number: US 12,178,902 B1
- Document ID: US12178902B1
- Status: Granted
- Kind: B1
- Application number: 17/146,935
- Filed: 2021-01-12
- Granted: 2024-12-31
- Earliest claimed: 2020-01-12
- Assignees: University of Southern California
- Applicants: University of Southern California
- Inventors: Young-Kwon Hong; Dong-Won Choi
- Web page: https://patentgrep.com/patent/US12178902B1

## CPC

- A61K 9/0009: {involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis}
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 31/497: containing further heterocyclic rings
- A61K 41/0047: {Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent}
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- 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

## Abstract

A method of treating impaired lymphatic function in a subject is provided. The method includes a step of inducing activation of Piezo1 ion channels in lymphatic tissues of a subject having impaired lymphatic function. Similarly, a method of treating ocular hypertension or glaucoma in a subject includes a step of inducing activation of Piezo1 ion channels in an eye of a subject having an ocular pressure that is greater than 22 mm Hg. Finally, a method of treating ocular hypertension or glaucoma in a subject includes a step of inducing activation of Piezo1 ion channels in an eye of a subject having an ocular pressure that is greater than 22 mm Hg.

## Claims

### Claim 1

A method of treating impaired lymphatic function in a subject, the method comprising the step of:
administering a pharmaceutical composition to the subject having dysfunctional lymphatic valves in lymphatic tissues to treat the dysfunctional lymphatic valves in the lymphatic tissues, wherein the pharmaceutical composition includes a Piezo1 agonist that is 2-[(2,6-dichlorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-thiadiazole, wherein administration of the pharmaceutical composition is in a sufficient amount to enhance expression of lymphatic valve-associated genes FOXC2, GATA2, CX37, and LAMA5 through Piezo1-dependent pathways, and to promote expression of ITGA9 through Piezo1-independent pathways, thereby promoting formation and function of lymphatic valves.

### Claim 2 (depends on 1)

The method of claim 1 further comprising applying oscillatory shear stress to the lymphatic tissues.

### Claim 3 (depends on 2)

The method of claim 2, wherein the oscillatory shear stress does not activate Piezo2 ion channels in the lymphatic tissues.

### Claim 4 (depends on 2)

The method of claim 2, wherein the applying step includes directing ultrasound pulses towards the lymphatic tissues.

### Claim 5 (depends on 4)

The method of claim 4, wherein the ultrasound pulses have a frequency of 43 megahertz (MHz).

### Claim 6

A method of treating ocular hypertension or glaucoma in a subject, the method comprising the step of:
administering a pharmaceutical composition to the subject having an ocular pressure that is greater than 22 mm Hg, wherein the pharmaceutical composition includes a Piezo1 agonist that is 2-[(2,6-dichlorophenyl)methylsulfanyl]-5-pyrazin-2-yl-1,3,4-thiadiazole, wherein the subject has ocular hypertension or glaucoma, wherein administration of the pharmaceutical composition is in a sufficient amount to enhance expression of lymphatic valve-associated genes FOXC2, GATA2, CX37, and LAMA5 through Piezo1-dependent pathways, and to promote expression of ITGA9 through Piezo1-independent pathways.

### Claim 7 (depends on 6)

The method of claim 6 further comprising applying oscillatory shear stress to the eye.

### Claim 8 (depends on 7)

The method of claim 7, wherein the oscillatory shear stress does not activate Piezo2 ion channels in the eye.

### Claim 9 (depends on 7)

The method of claim 7, wherein the applying step includes directing ultrasound pulses towards the eye.

### Claim 10 (depends on 9)

The method of claim 9, wherein the ultrasound pulses have a frequency of 43 megahertz (MHz).

### Claim 11 (depends on 7)

The method of claim 7, wherein the pharmaceutical composition is administered in an amount effective for reducing the ocular pressure.

### Claim 12 (depends on 6)

The method of claim 6, wherein the subject has glaucoma.