# US 12,599,577 B2 · Thermoresponsive gel eye drop for ocular delivery of cysteamine

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- Number: US 12,599,577 B2
- Document ID: US12599577B2
- Status: Granted
- Kind: B2
- Application number: 17/281,647
- Filed: 2019-11-18
- Published: 2021-12-02
- Granted: 2026-04-14
- Earliest claimed: 2018-11-16
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: Morgan Virginia Fedorchak; Steven R. Little; Joel S. Schuman
- Web page: https://patentgrep.com/patent/US12599577B2

## CPC

- A61K 9/0051: {Ocular inserts or implants}
- A61K 31/145: having sulfur, e.g. thiurams (>N—C(S)—S—C(S)—N< and >N—C(S)—S—S—C(S)—N<), Sulfinylamines (—N=SO), Sulfonylamines (—N=SO2) (isothiourea A61K31/155)
- A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)}
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 9/1647: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/1694: {resulting in granules or microspheres of the matrix type containing more than 5% of excipient}
- A61K 41/0028: {Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds}
- A61K 47/32: Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61P 27/02: Ophthalmic agents
- 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

This document provided ocular delivery systems for treatment of cystinosis as well as methods for making such ocular delivery systems and methods for using such ocular delivery systems. For example, ocular delivery systems designed to include spray-dried, cysteamine-loaded microparticles suspended in a thermoresponsive gel are provided herein.

## Claims

### Claim 1

An ocular delivery system for cysteamine, comprising:
a thermoresponsive gel comprising poly(N-isopropyl acrylamide) (PNIPAAm); and
a plurality of spray-dried microparticles comprising a biodegradable polymer and cysteamine or a pharmaceutically acceptable salt thereof, wherein said biodegradable polymer comprises poly(lactic-co-glycolic acid) (PLGA),
wherein at least 90 percent of said cysteamine or said pharmaceutically acceptable salt thereof is maintained within said ocular delivery system for at least seven weeks at 25° C.

### Claim 2 (depends on 1)

The ocular delivery system of claim 1, wherein the biodegradable polymer comprises polyglycolide (PGA), poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), or any combination thereof.

### Claim 3 (depends on 1)

The ocular delivery system of claim 1, wherein the cysteamine or the pharmaceutically acceptable salt thereof is homogeneously dispersed within the spray-dried microparticles.

### Claim 4 (depends on 1)

The ocular delivery system of claim 1, wherein the spray-dried microparticles have a volume average diameter within a range of from 200 nm to 10 μm.

### Claim 5 (depends on 1)

The ocular delivery system of claim 1, wherein the spray-dried microparticles comprise from 10-20 wt % cysteamine or an amount of a pharmaceutically acceptable salt of cysteamine sufficient to provide 10-20 wt % cysteamine.

### Claim 6 (depends on 1)

The ocular delivery system of claim 1, wherein the PLGA has a weight average molecular weight within a range of 4-80 kDa.

### Claim 7 (depends on 1)

The ocular delivery system of claim 1, wherein the ocular delivery system comprises from 0.001 mg to 0.5 mg of the spray-dried microparticles per microliter of the ocular delivery system.

### Claim 8

An ocular delivery system for cysteamine made by a process comprising:
providing a liquid feedstock comprising cysteamine or a pharmaceutically acceptable salt thereof, a biodegradable polymer, and a solvent, wherein the biodegradable polymer comprises poly(lactic-co-glycolic acid) (PLGA);
directing the liquid feedstock to a spray-drying apparatus comprising a drying chamber comprising an inlet and an outlet, a nozzle coupled to the inlet, a spray gas source coupled to the nozzle, a separator coupled to the outlet of the drying chamber, and an aspirator coupled to the separator;
atomizing the liquid feedstock into droplets as the liquid feedstock flows through the nozzle and into the drying chamber;
removing at least a portion of the solvent from the droplets in the drying chamber, thereby forming a plurality of spray-dried microparticles, wherein the spray-dried microparticles comprise a solid dispersion of the cysteamine, or the pharmaceutically acceptable salt thereof, and the biodegradable polymer;
collecting the spray-dried microparticles; and
dispersing the spray-dried microparticles in a thermoresponsive gel comprising poly(N-isopropyl acrylamide) (PNIPAAm) to form an ocular delivery system for cysteamine,
wherein at least 90 percent of said cysteamine or said pharmaceutically acceptable salt thereof is maintained within said ocular delivery system for at least seven weeks at 25° C.