Topical vasoconstrictor preparations and methods for protecting cells during cancer chemotherapy and radiotherapy

Patent metadata

Field	Value
Publication number	US-2016136113-A1
Application number	US-201514934275-A
Country	US
Kind code	A1
Filing date	Nov 6, 2015
Priority date	Jun 17, 2005
Publication date	May 19, 2016
Grant date	—

Abstract

Vasoconstrictors are administered topically to provide protection against the adverse effects, e.g., alopecia, mucositis or dermatitis, induced by chemotherapy or radiotherapy. Appropriate dosages and formulations of topical vasoconstrictors are provided. Methods for the use of such compositions are also provided.

First claim

What is claimed is:

1 . A method for reducing at least one condition of alopecia, dermatitis, mucositis, gastrointestinal distress, or proctitis in a patient treated or to be treated with a chemotherapeutic agent, radiation therapy, or a combination thereof, comprising topically administering to the patient a preparation comprising a vasoconstrictor in a pharmaceutically-acceptable delivery vehicle in an amount effective to reduce the at least one condition.

2 . The method of claim 1 , wherein the at least one condition is reduced in one or more non-neoplastic cells of the skin, scalp, mouth, rectum, nasoesophageal system, gastrointestinal system, or urogenital system.

3 . The method of claim 1 , wherein the preparation is delivered to a cell within a tissue selected from the group consisting of esophagus, stomach, intestines, rectum, skin, and oral mucosa.

4 . The method of claim 1 , wherein the vasoconstrictor is selected from the group consisting of epinephrine, phenylephrine, methoxamine, norepinephrine, zolmitriptan, tetrahydrozoline, naphazoline, oxidesumitriptan, avitriptan, rizatriptan, almotriptan, frovatriptan, capoten, enalapril, lisinopril, procainimide, nitric oxide, and any combination thereof.

5 . A pharmaceutical preparation comprising at least one vasoconstrictor in a pharmaceutically-acceptable topical delivery vehicle suitable for topically delivering the vasoconstrictor to a cell selected from the group consisting of a gastrointestinal cell, a nasoesophageal cell, a urogenital cell, a skin cell, and a mouth cell.

6 . The pharmaceutical preparation of claim 5 , wherein the delivery vehicle is suitable for topically delivering the vasoconstrictor to a cell within a tissue selected from the group consisting of esophagus, stomach, intestines, rectum, skin, and oral mucosa.

7 . The pharmaceutical preparation of claim 5 , wherein the preparation comprises a gel, a mucoadhesive coating, a suppository, or a foam preparation.

8 . The pharmaceutical preparation of claim 5 , wherein the preparation further comprises a flavoring agent in an amount effective to reduce, mask, or eliminate taste of the vasoconstrictor.

9 . The pharmaceutical preparation of claim 5 , wherein the delivery vehicle comprises water and an alcohol.

10 . The pharmaceutical preparation of claim 5 , wherein the vasoconstrictor is selected from the group consisting of epinephrine, phenylephrine, methoxamine, norepinephrine, zolmitriptan, tetrahydrozoline, naphazoline, oxidesumitriptan, avitriptan, rizatriptan, almotriptan, frovatriptan, capoten, enalapril, lisinopril, procainimide, nitric oxide, and any combination thereof.

11 . A method of delivering a vasoconstrictor to a squamous cell in a subject comprising topically administering to the subject a composition comprising a vasoconstrictor in a pharmaceutically-acceptable delivery vehicle, wherein the delivery vehicle is specifically formulated to allow vasoconstrictor penetration of the squamous skin.

12 . The method of claim 11 , wherein the vasoconstrictor is delivered to the underlying dermal vasculature that serves epidermal and hair follicle stem cells.

13 . The method of claim 11 , wherein the vasoconstrictor penetrates the stratum corneum or hair follicle sebum residue.

14 . The method of claim 11 , wherein the delivery vehicle comprises water and an alcohol.

15 . A topical vasoconstrictor formulation comprising a vasoconstrictor dissolved in a pharmaceutically-acceptable topical delivery vehicle that comprises water and at least 10% alcohol, wherein the vasoconstrictor is norepinephrine at a concentration of between about 4.5 mM and about 1500 mM, phenylephrine at a concentration of between about 10 mM and about 5000 mM, epinephrine at a concentration of between about 5 mM and about 1500 mM, or methoxamine at a concentration of between about 10 mM and about 5000 mM.

16 . The topical formulation of claim 15 , wherein the vasoconstrictor is norepinephrine.

17 . The topical formulation of claim 16 , wherein the norepinephrine is present at a concentration of about 200 to 800 mM.

18 . The topical formulation of claim 16 , wherein the norepinephrine is present at a concentration of about 450 to about 750 mM.

19 . The topical formulation of claim 16 , wherein the norepinephrine is present at a concentration of about 450 mM.

20 . The topical formulation of claim 15 , wherein the vasoconstrictor is phenylephrine present at a concentration of about 250 mM to about 2500 mM.

21 . The topical formulation of claim 15 , wherein the vasoconstrictor is phenylephrine present at a concentration of between about 10 mM and 100 mM, between about 50 mM and 250 mM, or between about 100 and 500 mM.

22 . The topical formulation of claim 21 , wherein the phenylephrine is present at a concentration of about 10 mM, about 50 mM, about 100 mM, or about 250 mM.

23 . The topical formulation of claim 21 , wherein the delivery vehicle comprises up to 90% alcohol.

24 . The topical formulation of claim 21 , wherein the delivery vehicle comprises at least 55% alcohol.

25 . The topical formulation of claim 21 , wherein the alcohol is ethanol, propylene glycol, polyethylene glycol, isopropanol, methanol, butanediol, or any combination thereof.

26 . The topical formulation of claim 21 , wherein the delivery vehicle comprises ethanol, propylene glycol, and water.

27 . The topical formulation of claim 21 , wherein the delivery vehicle comprises water and a mixture of at least two alcohols.

28 . The topical formulation of claim 21 , further comprising a sweetener or flavoring agent in an amount effective to reduce, mask, or eliminate taste of the vasoconstrictor.

29 . The topical formulation of claim 15 , wherein the vasoconstrictor is epinephrine present at a concentration of between about 5 mM and about 1500 mM.

30 . The topical formulation of claim 29 , wherein the epinephrine is present at a concentration of between about 5 and about 100 mM.

31 . The topical formulation of claim 29 , wherein the epinephrine is present at a concentration of between about 50 and about 250 mM.

32 . The topical formulation of claim 29 , wherein the epinephrine is present at a concentration of between about 100 mM and about 1000 mM.

33 . The topical formulation of claim 29 , further comprising a sweetener or flavoring agent in an amount effective to reduce, mask, or eliminate taste of the vasoconstrictor.

34 . The topical formulation of claim 15 , wherein the delivery vehicle comprises 55% alcohol.

35 . The topical formulation of claim 15 , wherein the delivery vehicle comprises 70% alcohol.

36 . The topical formulation of claim 15 , wherein the alcohol is ethanol, propylene glycol, polyethylene glycol, isopropanol, methanol, butanediol, or any combination thereof.

37 . The topical formulation of claim 15 , wherein the delivery vehicle comprises ethanol and water.

38 . The topical formulation of claim 15 , wherein the delivery vehicle comprises alcohol and water in a ratio of 70-80:20-30.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Fahl William E
• Ruoho Arnold E
• Mehta Minesh

Classifications

• A61P39/00

  General protective or antinoxious agents · CPC title

• A61P9/08

  Vasodilators for multiple indications · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title