# US 9,517,218 B2 · Methods and compositions for treating raynaud's disease

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- Number: US 9,517,218 B2
- Document ID: US9517218B2
- Status: Granted
- Kind: B2
- Application number: 14/591,487
- Filed: 2015-01-07
- Published: 2016-03-24
- Granted: 2016-12-13
- Earliest claimed: 2011-04-07
- Assignees: Nexmed Holdings, Inc.
- Applicants: Nexmed Holdings, Inc.
- Inventors: Daniel W. Frank; Richard Martin; Bassam B. Damaj
- Web page: https://patentgrep.com/patent/US9517218B2

## CPC

- A61K 31/191: having two or more hydroxy groups, e.g. gluconic acid
- A61J 1/05: for collecting, storing or administering blood, plasma or medical fluids {(multiple bags systems for separating or storing blood components A61M1/0209); Infusion or perfusion containers}
- 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 31/201: having one or two double bonds, e.g. oleic, linoleic acids
- A61K 31/5575: having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61P 9/08: Vasodilators for multiple indications
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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)
- A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

In various embodiments, methods and compositions for treating Raynaud's disease and Raynaud's phenomenon are provided. Topical administration of a semisolid composition comprising a prostaglandin E1 compound provides the desired relief of the Raynaud's disease or Raynaud's phenomenon without the possible complications of systemic administration. The semisolid composition can be administered as needed, or in a regimen of several doses per day.

## Claims

### Claim 1

A method of treating Raynaud's phenomenon in a subject comprising:
administering a semisolid composition comprising a prostaglandin E1 compound to a surface of an affected body part of the subject, wherein
the subject's Raynaud's Phenomenon is secondary to systemic sclerosis,
the total daily dose is divided into 1-4 doses, and
the total daily dose is administered in a regimen of one or more applications over the course of 12-24 hours.

### Claim 2 (depends on 1)

The method of claim 1 wherein the affected body part is one or both hands.

### Claim 3 (depends on 1)

The method of claim 1, wherein the composition further comprises a skin penetration enhancer that is selected from:
an N,N-di(C1-C8) alkylamino substituted (C4-C18) alkyl (C2-C18) carboxylic ester and pharmaceutically acceptable acid addition salts thereof; and
a (C1-C4)-alkyl (C8-C22) carboxylic ester.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition further comprises a thickening agent selected from a polysaccharide gum and a chemically modified polysaccharide gum.

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition is stored at room temperature.

### Claim 6 (depends on 1)

The method of claim 1 wherein the composition is provided in a two-part unit dose container.

### Claim 7 (depends on 1)

The method of claim 1, wherein the semisolid composition comprises a total daily dose of about 0.945 mg to about 5.7 mg a prostaglandin E1 compound.

### Claim 8 (depends on 1)

The method of claim 1, wherein the total daily dose is divided into 2-4 doses.

### Claim 9

A method of treating Raynaud's phenomenon in a subject comprising:
administering a semisolid composition comprising a total daily dose of about 0.945 mg to about 5.7 mg a prostaglandin E1 compound to a surface of an affected body part of the subject, wherein the total daily dose is divided into 1-4 doses, and
the total daily dose is administered in a regimen of one or more applications over the course of 12-24 hours.

### Claim 10 (depends on 9)

The method of claim 9, wherein the affected body part is one or both hands.

### Claim 11 (depends on 9)

The method of claim 9, wherein the composition further comprises a skin penetration enhancer that is selected from:
an N,N-di(C1-C8) alkylamino substituted (C4-C18) alkyl (C2-C18) carboxylic ester and pharmaceutically acceptable acid addition salts thereof; and
a (C1-C4)-alkyl (C8-C22) carboxylic ester.

### Claim 12 (depends on 9)

The method of claim 9, wherein the composition further comprises a thickening agent selected from a polysaccharide gum and a chemically modified polysaccharide gum.

### Claim 13 (depends on 9)

The method of claim 9, wherein the composition is stored at room temperature.

### Claim 14 (depends on 9)

The method of claim 9, wherein the composition is provided in a two-part unit dose container.

### Claim 15 (depends on 9)

The method of claim 9, wherein the subject's Raynaud's Phenomenon is secondary to systemic sclerosis.

### Claim 16 (depends on 9)

The method of claim 9, wherein the total daily dose is divided into 2-4 doses.

### Claim 17 (depends on 1)

The method of claim 1, wherein the composition further comprises a skin penetration enhancer that is an N,N-di(C1-C8) alkylamino substituted (C4-C18) alkyl (C2-C18) carboxylic ester and pharmaceutically acceptable acid addition salts thereof.

### Claim 18 (depends on 9)

The method of claim 9, wherein the composition further comprises a skin penetration enhancer that is an N,N-di(C1-C8) alkylamino substituted (C4-C18) alkyl (C2-C18) carboxylic ester and pharmaceutically acceptable acid addition salts thereof.

### Claim 19 (depends on 1)

The method of claim 1, wherein the composition further comprises a skin penetration enhancer that is dodecyl 2-(N,N-dimethylamino)-propionate (DDAIP).

### Claim 20 (depends on 1)

The method of claim 1, wherein the composition further comprises a skin penetration enhancer that is a pharmaceutically acceptable salt of dodecyl 2-(N,N-dimethylamino)-propionate (DDAIP).

### Claim 21 (depends on 9)

The method of claim 9, wherein the composition further comprises a skin penetration enhancer that is dodecyl 2-(N,N-dimethylamino)-propionate (DDAIP).

### Claim 22 (depends on 9)

The method of claim 9, wherein the composition further comprises a skin penetration enhancer that is a pharmaceutically acceptable salt of dodecyl 2-(N,N-dimethylamino)-propionate (DDAIP).