# US 9,040,061 B2 · Topical formulation for administering a compound

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,040,061 B2
- Document ID: US9040061B2
- Status: Granted
- Kind: B2
- Application number: 13/707,264
- Filed: 2012-12-06
- Published: 2013-06-13
- Granted: 2015-05-26
- Earliest claimed: 2011-12-08
- Assignees: Rigel Pharmaceuticals, Inc.
- Applicants: Rigel Pharmaceuticals, Inc.
- Inventors: Thomas Sun; Matt Duan
- Web page: https://patentgrep.com/patent/US9040061B2

## CPC

- A61K 31/635: having a heterocyclic ring, e.g. sulfadiazine
- A61K 9/0014: {Skin, i.e. galenical aspects of topical compositions (non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00)}
- A61K 31/505: Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 37/02: Immunomodulators
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

Embodiments of topical formulations for administering compound I or a pharmaceutically acceptable salt or solvate thereof are disclosed. Embodiments of methods for using the topical formulations in the treatment of dermatological disorders such as cutaneous collagen vascular diseases, e.g., cutaneous lupus, also are disclosed.

## Claims

### Claim 1

A pharmaceutical ointment formulation for topical administration, comprising:
a therapeutically effective amount of from about 0.1% to about 10% (w/w) of compound I having a formula
or a pharmaceutically acceptable salt thereof;
from 15% to 40% (w/w) of a topical base comprising polyethylene glycol having an average molecular weight of from about 3000 to about 8000 daltons;
from 0.5% to 1.5% (w/w) of an antioxidant;
from 3% to 15% (w/w) of an emollient;
from 10% to 20% (w/w) of a penetration enhancer;
from 25% to 50% (w/w) of a water-miscible solvent;
from 3% to 9% (w/w) of a surfactant; and
from 0.05% to 0.25% (w/w) of a colorant.

### Claim 2 (depends on 1)

The pharmaceutical formulation of claim 1, comprising:
from 0.2% to 6% (w/w) of compound I or a pharmaceutically acceptable salt thereof;
from 30% to 40% (w/w) polyethylene glycol with an average molecular weight from 4000-5000 daltons;
from 30% to 40% (w/w) polyethylene glycol with an average molecular weight from 300 to 500 daltons;
15% (w/w) dimethyl isosorbide;
3% to 5% (w/w) water;
5% (w/w) polyethylene glycol monostearate;
1% (w/w) butylated hydroxytoluene; and
from 0.05% to 0.25% (w/w) of the colorant.

### Claim 3 (depends on 1)

The pharmaceutical formulation of claim 1, comprising 1% (w/w) compound I, from 25% to 40% (w/w) polyethylene glycol with an average molecular weight of 4500 daltons, and from 30% to 45% (w/w) polyethylene glycol with an average molecular weight of 400 daltons.

### Claim 4 (depends on 1)

The pharmaceutical formulation of claim 1, comprising 3% (w/w) compound I, 32% (w/w) polyethylene glycol with an average molecular weight of 4500 daltons, and from 38% to 42% (w/w) polyethylene glycol with an average molecular weight of 400 daltons.

### Claim 5 (depends on 1)

The pharmaceutical formulation of claim 1, comprising 6% (w/w) compound I, 35% (w/w) polyethylene glycol with an average molecular weight of 4500 daltons, and from 33% to 35% (w/w) polyethylene glycol with an average molecular weight of 400 daltons.

### Claim 6 (depends on 1)

The pharmaceutical formulation of claim 1, comprising 1% (w/w) compound I, 20% (w/w) polyethylene glycol with an average molecular weight of 4500 daltons, and 48% (w/w) polyethylene glycol with an average molecular weight of 400 daltons.

### Claim 7 (depends on 1)

The pharmaceutical formulation of claim 1, comprising 3% (w/w) compound I, 20% (w/w) polyethylene glycol with an average molecular weight of 4500 daltons, and 46% (w/w) polyethylene glycol with an average molecular weight of 400 daltons.

### Claim 8 (depends on 1)

The pharmaceutical formulation of claim 1, comprising 6% (w/w) compound I, 20% (w/w) polyethylene glycol with an average molecular weight of 4500 daltons, and 43% (w/w) polyethylene glycol with an average molecular weight of 400 daltons.

### Claim 9 (depends on 1)

The pharmaceutical formulation of claim 1, where the water-miscible solvent is a polyalkylene glycol with an average molecular weight from 200-600 daltons.

### Claim 10 (depends on 1)

The pharmaceutical formulation according to claim 1 where the water-miscible solvent comprises PEG-400.

### Claim 11 (depends on 10)

The pharmaceutical formulation according to claim 10 wherein the PEG-400 is substantially free of impurities.

### Claim 12 (depends on 11)

The pharmaceutical formulation according to claim 11 wherein the PEG-400 comprises less than about 65 ppm formaldehyde.

### Claim 13 (depends on 11)

The pharmaceutical formulation according to claim 11 wherein the PEG-400 comprises less than about 10 ppm formaldehyde.

### Claim 14 (depends on 11)

The pharmaceutical formulation according to claim 11 wherein the PEG-400 comprises 1 ppm or less formaldehyde.

### Claim 15 (depends on 1)

The pharmaceutical formulation of claim 1, where the penetration enhancer is dimethyl isosorbide, propylene glycol, or a combination thereof.

### Claim 16 (depends on 1)

The pharmaceutical formulation of claim 1, where the emollient comprises water.

### Claim 17 (depends on 1)

The pharmaceutical formulation of claim 1, where the surfactant is a sorbitan monostearate, a polyethylene glycol monostearate, D-α-tocopheryl polyethylene glycol 1000 succinate, a composition comprising glycol stearate/PEG32 stearate/PEG6 stearate, or a combination thereof.

### Claim 18 (depends on 1)

The pharmaceutical formulation of claim 1, wherein the antioxidant is selected from the group consisting of butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, a tocopherol and combinations thereof.

### Claim 19 (depends on 18)

The pharmaceutical formulation of claim 18, where the antioxidant is butylated hydroxytoluene.

### Claim 20 (depends on 1)

The pharmaceutical formulation of claim 1, where the colorant is 0.05-0.25% (w/w) caramel.

### Claim 21 (depends on 1)

The pharmaceutical formulation of claim 1, where the topical base comprises polyalkylene glycol having an average molecular weight from 4000-5000 daltons, the water-miscible solvent is a polyalkylene glycol having an average molecular weight of 300-500 daltons, the penetration enhancer is dimethyl isosorbide, the emollient is water, the surfactant is a polyethylene glycol monostearate, the antioxidant is butylated hydroxytoluene, and the colorant is caramel colorant.

### Claim 22 (depends on 1)

The pharmaceutical formulation of claim 1, further comprising a fragrance, an absorbent, an astringent, a binder, a buffering agent, a chelating agent, a film-forming agent, a conditioning agent, an opacifying agent, a protectant, or any combination thereof.

### Claim 23

A pharmaceutical ointment formulation, comprising:
3% (w/w) of compound I or a pharmaceutically acceptable salt thereof;
32% (w/w) polyethylene glycol 4500;
39.95% (w/w) polyethylene glycol 400;
15% (w/w) dimethyl isosorbide;
4% (w/w) water;
5% (w/w) polyoxyl stearate 100;
1% (w/w) butylated hydroxytoluene; and
0.05% caramel colorant.

### Claim 24

A pharmaceutical ointment formulation, comprising:
6% (w/w) of compound I or a pharmaceutically acceptable salt thereof;
35% (w/w) polyethylene glycol 4500;
33.95% (w/w) polyethylene glycol 400;
15% (w/w) dimethyl isosorbide;
4% (w/w) water;
5% (w/w) polyoxyl stearate 100;
1% (w/w) butylated hydroxytoluene; and
0.05% caramel colorant.

### Claim 25

A method of treating cutaneous lupus, comprising topically administering to a subject a pharmaceutical ointment formulation comprising:
from 0.1% to 10% (w/w) of a compound I having a formula
or a pharmaceutically effective salt thereof;
from 15% to 40% (w/w) of a topical base comprising polyethylene glycol having an average molecular weight of from about 3000 to about 8000 daltons;
from 25% to 50% (w/w) of a water-miscible solvent;
from 10% to 20% (w/w) of a penetration enhancer;
from 3% to 15% (w/w) of an emollient;
from 3% to 9% (w/w) of a surfactant;
from 0.5% to 1.5% (w/w) of an antioxidant; and
from 0.05% to 0.25% (w/w) of a colorant.

### Claim 26 (depends on 25)

The method of claim 25, comprising:
from 0.2% to 6% (w/w) of compound I or a pharmaceutically acceptable salt thereof;
from 30% to 40% (w/w) polyethylene glycol with an average molecular weight from 4000-5000 daltons;
from 30% to 40% (w/w) polyethylene glycol with an average molecular weight from 300-500 daltons;
15% (w/w) dimethyl isosorbide;
3% to 5% (w/w) water;
5% (w/w) polyethylene glycol monostearate; and
1% (w/w) butylated hydroxytoluene.

### Claim 27 (depends on 26)

The method of claim 26, where the pharmaceutical formulation comprises 1% (w/w) compound I, 25% to 40% (w/w) polyethylene glycol with an average molecular weight of 4500 daltons, and 30% to 45% (w/w) polyethylene glycol with an average molecular weight of 400 daltons.

### Claim 28 (depends on 25)

The method of claim 25, where the subject has cutaneous lupus lesions, and the pharmaceutical formulation is applied topically to the cutaneous lupus lesions.