Nonsteroidal immunomodulating kit and composition and uses thereof

Patent metadata

Field	Value
Publication number	US-9668972-B2
Application number	US-7890205-A
Country	US
Kind code	B2
Filing date	Mar 11, 2005
Priority date	Oct 25, 2002
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

Abstract

Compositions and therapeutic kits including an aerosol container containing a foamable composition that includes a nonsteroidal immunomodulating agent are described. The foamable composition includes a liquid hydrophobic carrier; a surface-active agent; polymeric additive; water; and a propellant.

First claim

What is claimed is:

1. A therapeutic kit comprising an aerosol packaging assembly comprising:
a) a container accommodating a pressurized product; and
b) an outlet capable of releasing the pressurized product as a foam; wherein the pressurized product comprises:
(A) a foamable emulsion composition comprising:
i. a nonsteroidal immunomodulating agent;
ii. at least one liquid hydrophobic carrier at a concentration of about 20% to about 50% by weight;
iii. about 0.1% to about 5% by weight of surface active agent;
iv. about 0.01% to about 5% by weight of at least one polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent; and
v. water; and
(B) a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight;
wherein the pressurized product includes less than 5% or about 5% by weight of ethanol, propanol, isopropanol, butanol, iso-butanol, t-butanol, and pentanol, or mixtures of two or more thereof;
wherein the surface active agent comprises a non-ionic surface active agent and optionally an ionic surface active agent at a maximum amount of less than about 0.72% by weight;
wherein if ionic surfactant is present the ratio of non-ionic to ionic surface active agent is about 6:1 or greater than 6:1;
wherein the nonsteroidal immunomodulating agent is substantially or completely dissolved in the oil phase of the emulsion; and
wherein the pressurized product is released from the container as an expanded, breakable foam that collapses upon application of shear force.

2. A therapeutic foamable composition comprising:
(a) an emulsion composition comprising:
i. a nonsteroidal immunomodulating agent;
ii. about 20% to about 50% by weight of a therapeutically active oil;
iii. about 0.1% to about 5% by weight of surface active agent;
iv. about 0.01% to about 5% by weight of at least one polymeric agent selected from the group consisting of a bioadhesive agent, a gelling agent, a film forming agent and a phase change agent; and
v. water; and
(b) a liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight;
wherein the foamable composition includes less than 5% or about 5% by weight of ethanol, propanol, isopropanol, butanol, iso-butanol, t-butanol and pentanol or mixtures thereof;
wherein the surface active agent comprises non-ionic surface active agent and optionally ionic surface active agent at a maximum amount of less than about 0.72% by weight;
wherein if ionic surfactant is present the ratio of non-ionic to ionic surface active agent is about 6:1 or greater than 6:1;
wherein the nonsteroidal immunomodulating agent is substantially or completely dissolved in the oil phase of the emulsion; and
wherein upon release from a pressurized canister the foamable composition forms an expanded, breakable foam that collapses upon application of shear force.

3. The kit of claim 1 , wherein the polymeric agent is a gelling agent and wherein the propellant is selected from the group consisting of a hydrocarbon, a fluorocarbon, and mixtures thereof.

4. The kit of claim 2 , wherein the polymeric agent is a gelling agent and wherein the propellant is selected from the group consisting of a hydrocarbon, a fluorocarbon, or mixtures thereof.

5. The kit of claim 3 , wherein the foamable composition is selected from the group consisting of an oil-in-water emulsion and a water-in-oil emulsion.

6. The kit of claim 5 , wherein the outlet comprises a valve.

7. The kit of claim 6 , wherein the valve comprises a stem with 1 to 4 apertures formed in the stem.

8. The kit of claim 7 , wherein each aperture formed in the stem has a diameter selected from the group consisting of (i) about 0.2 mm to about 1 mm; and (ii) about 0.3 mm to about 0.8 mm.

9. The kit of claim 7 , wherein the sum of areas of all apertures in the stem is selected from the group consisting of (i) between about 0.01 mm 2 and 1 mm 2 ; and (ii) between about 0.04 mm 2 and 0.5 mm 2 .

10. The kit of claim 5 , further comprising about 0.1% to about 5% by weight of a therapeutically active foam adjuvant selected from the group consisting of a fatty alcohol having 15 or more carbons in its carbon chain; a fatty acid having 16 or more carbons in its carbon chain; fatty alcohols, derived from beeswax and including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain; a fatty alcohol having at least one double bond; a fatty acid having at least one double bond; a branched fatty alcohol; a branched fatty acid; a fatty acid substituted with a hydroxyl group; cetyl alcohol; stearyl alcohol; arachidyl alcohol; behenyl alcohol; 1-triacontanol; hexadecanoic acid; stearic acid; arachidic acid; behenic acid; octacosanoic acid; 12-hydroxy stearic acid; and mixtures of two or more thereof.

11. The kit of claim 10 , wherein the pressurized product includes less than 2% or about 2% by weight of ethanol, propanol, isopropanol, butanol, iso-butanol, t-butanol and pentanol, or mixtures of two or more thereof.

12. The kit of claim 4 , wherein the nonsteroidal immunomodulating agent is selected from the group consisting of:
i. an indole, an indende acetic acid, a heteraryl acetic acid, an arylpropionic acid, an anthranilic acids, a fenamate, an enolic acid, a pyrazolidinedione, and an alkanone; and salts thereof;
ii. salicylic acid, aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, salicylsalicylic acid, sulfasalazine, olsalazine, esters of salicylic acid with a carboxylic acid, esters of salicylic acid with a dicarboxylic acid, esters of salicylic acid with a fatty acid, esters of salicylic acid with a hydroxyl fatty acid, esters of salicylic acid with an essential fatty acid, esters of salicylic acid with a polycarboxylic acid, para-aminophenol, indole, indomethacin, sulindac, etodolac, tolmetin, diclofenac, ketorolac, ibuprofen, naproxen, flubiprofen, ketoprofen, fenoprofen, oxaprozin, mefenamic acid, meclofenamic acid, oxicams, piroxicam, tenoxicam, pyrazolidinediones, phenylbutazone, oxyphenthratrazone, nabumetone, diaryl-substituted furanones, Rofecoxib, diaryl-substituted pyrazoles, Celecoxib, indole acetic acids, Etodolac, sulfonanilides, Nimesulide, and salts and analogs thereof;
iii. an imidazole or triazole compound;
iv. ketoconazole;
v. a xanthine, pentoxifylline, propentofylline, torbafylline, amiloride, chloroquine, thalidomide, and salts and analogs thereof;
vi. a cyclic peptide, cyclosporine, tacrolimus, tresperimus, pimecrolimus, sirolimus, verolimus, laflunimus, laquinimod, and imiquimod;
vii. a dicarboxylic acid having between about 6 and about 14 carbon atoms in its carbon atom skeleton, and salts thereof;
viii. adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, 1,11-undecanedioic acid, 1,12-dodecanedioic acid, 1,13-tridecanedioic acid, and 1,14-tetradecanedioic acid;
ix. azelaic acid; and
x. a dicarboxylic acid covalently linked with at least one moiety selected from the group consisting of alpha-hydroxy acid, beta-hydroxy acid, hydroxybenzoic acid, alkylhydroxybenzoate, dihydroxy benzene, cresol, alcohol derivatives of Vitamin A, retinoic acid, retinal, steroid hormones, corticosteroids, vitamin E, and vitamin D, and analogs thereof.

13. The kit of claim 10 , wherein the concentration range of the nonsteroidal immunomodulating agent is selected from the group consisting of (i) between about 0.05% and about 2% by weight; (ii) between about 2% and about 5% by weight; (iii) between about 5% and about 12% by weight; and (iv) between about 12% and about 24% by weig

Assignees

• Tamarkin Dov
• Eini Meir
• Friedman Doron
• Foamix Pharmaceuticals Ltd

Inventors

• Tamarkin Dov
• Eini Meir
• Friedman Doron

Classifications

• A61K9/10

  Dispersions; Emulsions · CPC title

• A61K9/122 Primary

  Foams; Dry foams (edible foams A61K9/0056) · CPC title

• A61K8/046

  Aerosols; Foams · CPC title

• A61K31/07

  Retinol compounds, e.g. vitamin A (retinoic acids A61K31/203) · CPC title

• A61Q19/00

  Preparations for care of the skin · CPC title