# US 10,945,948 B2 · Compositions and methods for ophthalmic and/or other applications

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- Number: US 10,945,948 B2
- Document ID: US10945948B2
- Status: Granted
- Kind: B2
- Application number: 16/988,459
- Filed: 2020-08-07
- Published: 2020-11-26
- Granted: 2021-03-16
- Earliest claimed: 2012-05-03
- Assignees: The Johns Hopkins University
- Applicants: The Johns Hopkins University
- Inventors: Alexey Popov; Elizabeth M. Enlow; Hongming Chen; James Bourassa
- Web page: https://patentgrep.com/patent/US10945948B2

## CPC

- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- A61K 9/5123: {Organic compounds, e.g. fats, sugars}
- A61K 9/5138: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61K 31/56: Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- 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

Particles, compositions, and methods that aid particle transport in mucus are provided. The particles, compositions, and methods may be used, in some instances, for ophthalmic and/or other applications. In some embodiments, the compositions and methods may involve modifying the surface coatings of particles, such as particles of pharmaceutical agents that have a low aqueous solubility. Such compositions and methods can be used to achieve efficient transport of particles of pharmaceutical agents though mucus barriers in the body for a wide spectrum of applications, including drug delivery, imaging, and diagnostic applications. In certain embodiments, a pharmaceutical composition including such particles is well-suited for ophthalmic applications, and may be used for delivering pharmaceutical agents to the front of the eye and/or the back of the eye.

## Claims

### Claim 1

A method for treating an eye disorder in a patient in need thereof comprising:
administering via topical instillation into an eye of the patient a ophthalmic suspension comprising:
(a) a plurality of coated nanoparticles, wherein each of the coated nanoparticles comprises:
(i) a core particle comprising loteprednol etabonate, wherein the loteprednol etabonate comprises at least 80 wt % of the core particle; and
(ii) poloxamer 407 non-covalently adsorbed to the core particle;
(b) sodium chloride;
(c) glycerin;
(d) disodium ethylenediaminetetraacetic acid;
(e) sodium citrate;
(f) citric acid; and
(g) water;
wherein the ophthalmic suspension comprises about 0.25% w/v loteprednol etabonate;
wherein the pH of the ophthalmic suspension is at least 5 and less than or equal to about 7;
wherein the eye disorder treated is a dry eye condition;
wherein the ophthalmic suspension is formulated as an eye drop; and
wherein the administration of the ophthalmic suspension occurs four times daily.

### Claim 2 (depends on 1)

The method of claim 1, wherein the ophthalmic suspension further comprises benzalkonium chloride.

### Claim 3 (depends on 2)

The method of claim 2, wherein:
the poloxamer 407 is present in the ophthalmic suspension in an amount of about 0.01% w/v to about 2% w/v;
the sodium chloride is present in the ophthalmic suspension in an amount of about 0.1% w/v to about 1% w/v;
the glycerin is present in the ophthalmic suspension in an amount of about 0.5% w/v to about 3% w/v;
the disodium ethylenediaminetetraacetic acid is present in the ophthalmic suspension in an amount of about 0.001% w/v to about 0.1% w/v; and
the benzalkonium chloride is present in the ophthalmic suspension in an amount of about 0.001% w/v to about 0.05% w/v.

### Claim 4 (depends on 3)

The method of claim 3, wherein the ratio of the weight of the loteprednol etabonate present in the ophthalmic suspension to the weight of the poloxamer 407 present in the ophthalmic suspension is greater than or equal to about 1:1, and less than or equal to about 3:1.

### Claim 5 (depends on 3)

The method of claim 3, wherein the poloxamer 407 is present in the ophthalmic suspension in an amount of about 0.125% w/v.

### Claim 6 (depends on 5)

The method of claim 5, wherein:
the sodium chloride is present in the ophthalmic suspension in an amount of about 0.45% w/v to about 0.9% w/v;
the glycerin is present in the ophthalmic suspension in an amount of about 0.6% w/v; and
the disodium ethylenediaminetetraacetic acid is present in the ophthalmic suspension in an amount of about 0.01% w/v to 0.1% w/v.

### Claim 7 (depends on 6)

The method of claim 6, wherein the osmolality of the ophthalmic suspension is about 300 mOsm/kg.

### Claim 8 (depends on 6)

The method of claim 6, wherein the ophthalmic suspension has an osmolarity of about 250 mOsm/L to about 310 mOsm/L.

### Claim 9 (depends on 6)

The method of claim 6, wherein administration of the ophthalmic suspension comprises instillation of one to two drops of the ophthalmic suspension into each eye of the patient.

### Claim 10 (depends on 6)

The method of claim 6, wherein the ophthalmic suspension is a sterile ophthalmic composition and comprises less than or equal to about 0.5 wt % 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-4-ene-17-carboxylic acid chloromethyl ester relative to the weight of the loteprednol etabonate in the ophthalmic suspension.

### Claim 11 (depends on 6)

The method of claim 6, wherein administration of the ophthalmic suspension reduces the patient's ocular discomfort.

### Claim 12 (depends on 1)

The method of claim 1, wherein the core particle is substantially free of a polymeric component.

### Claim 13 (depends on 1)

The method of claim 1, wherein:
the osmolality of the ophthalmic suspension is about 300 mOsm/kg; and
administration of the ophthalmic suspension comprises instillation of one to two drops into each eye of the patient.

### Claim 14 (depends on 13)

The method of claim 13, wherein administration of the ophthalmic suspension reduces the patient's ocular discomfort.

### Claim 15 (depends on 3)

The method of claim 3, wherein:
the osmolality of the ophthalmic suspension is about 300 mOsm/kg; and
administration of the ophthalmic comprises instillation of one to two drops into each eye of the patient.

### Claim 16 (depends on 15)

The method of claim 15, wherein administration of the ophthalmic suspension reduces the patient's ocular discomfort.

### Claim 17 (depends on 1)

The method of claim 1, wherein the poloxamer 407 is present on the loteprednol etabonate nanoparticles at an average density of at least 0.01 molecules/nm2 and less than 10 molecule/nm2.

### Claim 18 (depends on 6)

The method of claim 6, wherein the poloxamer 407 is present on the loteprednol etabonate nanoparticles at an average density of at least 0.05 molecules/nm2 and less than 10 molecule/nm2.

### Claim 19 (depends on 6)

The method of claim 6, wherein the loteprednol etabonate comprises at least 90 wt % of the core particle.

### Claim 20 (depends on 6)

The method of claim 6, wherein the loteprednol etabonate comprises at least 95 wt % of the core particle.

### Claim 21 (depends on 6)

The method of claim 6, wherein the loteprednol etabonate comprises at least 99 wt % of the core particle.