Oleaginous pharmaceutical and cosmetic foam

Abstract

The invention relates to stable oleaginous cosmetic or therapeutic foam compositions containing certain active agents, having unique therapeutic properties and methods of treatment using such compositions. The foamable composition includes at least one solvent selected from a hydrophobic solvent, a silicone oil, an emollient, a co-solvent, and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition, at least a non-ionic surface-active agent at a concentration of about 0.1% to less than about 10% by weight of the total composition; at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition; a therapeutically effective amount of at least one active agent; and at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of the total composition.

1 . An oleaginous foamable therapeutic composition, comprising: 
 a. at least one solvent selected from a hydrophobic solvent, a silicone oil, an emollient, a co-solvent, and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition;    b. at least a non-ionic surface-active agent at a concentration of about 0.1% to less than about 10% by weight of the total composition;    c. at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition;    d. a therapeutically effective amount of at least one active agent;    e. at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of the total composition.    
   
   
       2 . The oleaginous composition of  claim 1 , comprising less than about 5% of a lower alcohol, having up to 5 carbon atoms in its carbon chain skeleton.  
   
   
       3 . The oleaginous composition of  claim 1 , further comprising a foam adjuvant selected from the group consisting of fatty alcohols having greater than or equal to 15 carbons and fatty acids having greater than or equal to 16 carbons.  
   
   
       4 . The oleaginous composition of  claim 1 , wherein the at least one solvent comprises a hydrophobic solvent having solubility in distilled water at ambient temperature of less than about one gram per 100 ml.  
   
   
       5 . The oleaginous composition of  claim 1 , wherein the at least one solvent comprises a hydrophobic solvent selected from the group consisting of mineral oils, triglyceride oils, silicone oils, polyunsaturated oils, unsaturated oils and essential oils.  
   
   
       6 . The oleaginous composition of  claim 1 , wherein the at least one solvent comprises a mixture of at least one hydrophobic solvent and at least one co-solvent.  
   
   
       7 . The oleaginous composition of  claim 6 , wherein the mixture of at least one hydrophobic solvent and the at least one co-solvent comprises a weight ratio of about 1:8 to about 8:1.  
   
   
       8 . The oleaginous composition of  claim 7 , wherein the mixture forms an emulsion.  
   
   
       9 . The oleaginous composition of  claim 7 , wherein the at least one co-solvent comprises glycerin.  
   
   
       10 . The oleaginous composition of  claim 9 , wherein the mixture of at least one hydrophobic solvent and glycerin comprises a weight ratio of about 1:4 to about 4:1.  
   
   
       11 . The oleaginous composition of  claim 9 , wherein the mixture of at least one hydrophobic solvent and glycerin comprises a weight ratio of about 1:2 to about 2:1.  
   
   
       12 . The oleaginous composition of claims  1  and  6 , wherein the co-solvent comprises a polyethylene glycol.  
   
   
       13 . The oleaginous composition of  claim 1 , wherein the at least one solvent comprises a potent solvent selected from a hydrophobic solvent other than mineral oil, a co-solvent and an emollient, wherein the potent solvent solubilizes the active agent substantially better than mineral oil solubilizes the active agent.  
   
   
       14 . The oleaginous composition of  claim 13 , wherein the potent solvent solubilizes the active agent at least 5-fold better than mineral oil solubilizes the active agent.  
   
   
       15 . The oleaginous composition of  claim 13 , wherein the potent solvent solubilizes the active agent at least 10-fold better than mineral oil solubilizes the active agent.  
   
   
       16 . The oleaginous composition of  claim 13 , wherein the potent solvent is selected from the group consisting of polyethylene glycol, propylene glycol, hexylene glycol, butanediols and isomers thereof, glycerol, benzyl alcohol, DMSO, ethyl oleate, ethyl caprylate, diisopropyl adipate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyethylpyrrolidone, polyvinylpyrrolidone, isosorbide derivatives, dimethyl isosorbide, glycofurol and ethoxydiglycol (transcutol).  
   
   
       17 . The oleaginous composition of  claim 1 , further comprising a mixture of a non-ionic surface-active agent and an ionic surface-active agent.  
   
   
       18 . The oleaginous composition of  claim 17 , wherein the mixture of the non-ionic surface-active agent and the ionic surface-active agent is present at a weight ratio of about 20:1 to about 1:1 non-ionic surfactant to ionic surfactant.  
   
   
       19 . The oleaginous composition of  claim 1 , wherein the concentration of the surface-active agent is less than about 2%.  
   
   
       20 . The oleaginous composition of  claim 1 , wherein the surface-active agent comprises a phospholipid.  
   
   
       21 . The oleaginous composition of  claim 20 , wherein the phospholipid comprises phosphatidylcholine.  
   
   
       22 . The oleaginous composition of  claim 1 , wherein the at least one gelling agent is selected from the group consisting of natural polymeric materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents and mixtures thereof.  
   
   
       23 . The oleaginous composition of  claim 1 , wherein the water content is less than about 30% by weight.  
   
   
       24 . The oleaginous composition of  claim 1 , wherein the water content is less than about 20% by weight.  
   
   
       25 . The oleaginous composition of  claim 1 , wherein the composition is contained within a pressurized container.  
   
   
       26 . The oleaginous composition of  claim 1  having a specific gravity of about 0.01 gr/ml to about 0.3 gr/mL upon release from the pressurized container.  
   
   
       27 . The oleaginous composition of  claim 1 , wherein the active agent is selected to treat a dermatological or mucosal disorder that is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant and combinations thereof.  
   
   
       28 . The oleaginous composition of  claim 1  wherein the active agent is a component of the foamable composition selected from a solvent, a surface-active agent, a gelling agent and a foam adjuvant.  
   
   
       29 . The oleaginous composition of  claim 1 , wherein the at least one active agent is selected from a therapeutic agent and a cosmetic agent.  
   
   
       30 . The oleaginous composition of  claim 29 , wherein the at least one therapeutic agent is selected from an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, an antiinflammatory agent, an immunosuppressive agent, and immunomodulator, an immuno regulating agent, an anesthetic, an analgesic, an antiallergic agent, a corticosteroid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, a lubricating agent and mixtures thereof.  
   
   
       31 . The oleaginous composition of  claim 29 , wherein the therapeutic agent is selected for the treatment of a disorder of the skin, mucosal membrane, ear channel, vagina, penile urethra, colon and rectum.  
   
   
       32 . The oleaginous composition of  claim 29 , wherein the cosmetic agent is selected from a retinoid, an anti-wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent, a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent.  
   
   
       33 . The oleaginous composition of  claim 29 , wherein the therapeutic agent is intended for transdermal delivery.  
   
   
       34 . The oleaginous composition of  claim 1 , wherein the at least one active agent is an inorganic solid matter.  
   
   
       35 . The oleaginous composition of  claim 34 , wherein the inorganic solid matter is a metal oxide for forming a protective layer on a body surface or a mucosal membrane.  
   
   
       36 . A stable oleaginous foamable water-in-oil emulsion, comprising 
 a. at least one solvent selected from a hydrophobic solvent, a co-solvent and an emollient at a concentration of about 30% to about 96.5% by weight;    b. water;    c. at least one non-ionic lipophilic surface-active agent having an HLB value of about 3 to about 10 at a concentration of about 0.1% to less than about 10% by weight,    d. at least one gelling agent at a concentration of about 0.1% to about 5% by weight;    e. a therapeutically effective amount of at least one active agent; and    f. at least one liquefied or compressed gas propellant at a concentration of about 3% to about 25% by weight of the total composition.    
   
   
       37 . The oleaginous composition of  claim 36 , comprising less than about 5% of a lower alcohol, having up to 5 carbon atoms in its carbon chain.  
   
   
       38 . The oleaginous emulsion of  claim 36 , further comprising a foam adjuvant selected from the group consisting of fatty alcohols having greater than or equal to 15 carbons and fatty acids having greater than or equal to 16 carbons.  
   
   
       39 . The oleaginous emulsion of  claim 36 , wherein the at least one solvent comprises a hydrophobic solvent having solubility in distilled water at ambient temperature of less than about one gram per 100 ml.  
   
   
       40 . The oleaginous emulsion of  claim 39 , wherein the hydrophobic solvent is selected from mineral oil, a triglyceride oil, an ester of a fatty acid, an ester of a dicarboxylic acid, a silicone oil, a polyunsaturated oil, an unsaturated oil and an essential oil.  
   
   
       41 . The oleaginous emulsion of  claim 36 , wherein the at least one hydrophobic solvent and water are present at a weight ratio in the range of about 1:3 to about 6:1.  
   
   
       42 . The oleaginous emulsion of  claim 36 , wherein the at least one solvent is a potent solvent selected from the group consisting of hydrophobic solvents other than mineral oil, co-solvents and emollients, wherein the potent solvent solubilizes an active agent substantially better than mineral oil solubilizes the active agent.  
   
   
       43 . The oleaginous emulsion of  claim 42 , wherein the potent solvent solubilizes the active agent at least 5-fold better than mineral oil solubilizes the active agent.  
   
   
       44 . The oleaginous emulsion of  claim 42 , wherein said potent solvent solubilizes the active agent at least 10-fold better than a mineral oil solubilizes the active agent.  
   
   
       45 . The oleaginous emulsion of  claim 42 , wherein the potent solvent is selected from the group consisting of polyethylene glycols, propylene glycols, hexylene glycols, butanediols and isomers thereof, glycerols, benzyl alcohol, DMSO, ethyl oleates, ethyl caprylates, diisopropyl adipate, dimethylacetamides, N-methylpyrrolidones N-hydroxyethylpyrrolidones, polyvinylpyrrolidones, an isosorbide derivatives, glycofurols and ethoxydiglycols (transcutol).  
   
   
       46 . The oleaginous emulsion of  claim 36 , wherein the concentration of the surface-active agent is less than about 2%.  
   
   
       47 . The oleaginous emulsion of  claim 46 , wherein surface-active agent is selected from the group consisting of sorbitan derivatives; alkoxylated alcohols; hydroxylated derivatives of polymeric silicones; alkylated derivatives of hydroxylated polymeric silicones; glyceryl esters; beeswax derivatives; lecithin; and mixtures thereof.  
   
   
       48 . The oleaginous emulsion of  claim 36 , wherein the at least one gelling agent is selected from the group consisting of natural polymeric materials, semi-synthetic polymeric materials, synthetic polymeric materials, inorganic gelling agents and mixtures thereof.  
   
   
       49 . The oleaginous emulsion of  claim 48 , wherein the inorganic gelling agent comprises silicone dioxide.  
   
   
       50 . The oleaginous emulsion of  claim 36 , having a specific gravity of about 0.01 gr/ml to about 0.3 gr/mL, upon extrusion from a pressured container.  
   
   
       51 . The oleaginous emulsion of  claim 36 , wherein the at least one active agent is a component of the foamable composition and is selected from a solvent, a surface-active agent, a gelling agent and a foam adjuvant.  
   
   
       52 . The oleaginous emulsion of  claim 36  wherein the at least one active agent is selected from an anti-infective, an antibiotic, an antibacterial agent, an antifungal agent, an antiviral agent, an antiparasitic agent, an antiinflammatory agent, an anesthetic, an analgesic, an antiallergic agent, a corticosteroid, a retinoid, an antiproliferative agent, an anticancer agent, a photodynamic therapy agent, an anti-wrinkle agent, a radical scavenger, a self-tanning agent, a skin whitening agent, a skin protective agent, an anti-cellulite agent, a massaging oil and an anti-wart agent, a refatting agent, a lubricating agent and mixtures thereof.  
   
   
       53 . The oleaginous emulsion of  claim 36 , wherein the therapeutic agent is selected for the treatment of a disorder of the skin, mucosal membrane, ear channel, vagina, penile urethra and rectum.  
   
   
       54 . The oleaginous emulsion of  claim 36 , wherein the active agent is intended for transdermal delivery.  
   
   
       55 . The oleaginous emulsion of  claim 36 , having the properties of breakable foam for treating, alleviating or preventing a dermatological or mucosal disorder.  
   
   
       56 . The oleaginous emulsion of  claim 55 , wherein the etiology the dermatological or mucosal disorder is bacterial, fungal, viral, parasitic, inflammatory, autoimmune, allergic, hormonal, malignant and combinations thereof.  
   
   
       57 . The oleaginous emulsion of  claim 36 , wherein the at least one active agent is an inorganic solid matter.  
   
   
       58 . The oleaginous emulsion of  claim 57 , wherein the inorganic solid matter is selected to form a protective layer on a body surface or a mucosal membrane.  
   
   
       59 . The oleaginous emulsion of  claim 57 , wherein the inorganic solid matter is selected to treat a skin disorder selected from sensitive skin, diaper rash and diaper dermatitis.  
   
   
       60 . The oleaginous emulsion of  claim 57 , further comprising at least one active agent, selected from antibacterial agent, antifungals agent and anti-inflammatory agent.  
   
   
       61 . A method of treating, alleviating or preventing a dermatological, cosmetic or mucosal disorder, comprising administering topically to a subject having said disorder a therapeutically effective amount of an oleaginous foam composition according to  claim 1  or  claim 36 .  
   
   
       62 . A method of designing a foamable composition, comprising at least one active agent that is substantially insoluble in mineral oil, comprising the steps of: 
 i. selecting at least one active agent; and    ii. identifying a solvent that solubilizes said at least one active agent substantially better than mineral oil solubilizes said at least one active agent, whereby the active agent is solubilized in the composition.    iii. adjusting the type and concentration of surfactant and gelling agent, to provide a foamable composition    
   
   
       63 . The method of  claim 62 , wherein the potent solvent solubilizes the active agent 5 fold better than a hydrocarbon solvent solubilizes the active agent.  
   
   
       64 . The method of  claim 62 , wherein the potent solvent solubilizes the active agent 10 fold better than a hydrocarbon solvent solubilizes the active agent.  
   
   
       65 . An oleaginous foamable therapeutic composition, essentially free of alcohol, comprising: 
 a. at least one solvent selected from a hydrophobic solvent, a co-solvent, and mixtures thereof, wherein the solvent is present at a concentration of about 70% to about 96.5% by weight of the total composition;    b. at least a non-ionic surface-active agent at a concentration of about 0.1% to about 25% by weight of the total composition, wherein the surface-active agent comprises a phospholipid;    c. at least one gelling agent at a concentration of about 0.1% to about 5% by weight of the total composition;    d. a therapeutically effective amount of at least one active agent;    e. at least one liquefied or compressed gas propellant, at a concentration of about 3% to about 25% by weight of the total composition.    
   
   
       66 . The composition of  claim 65 , wherein the phospholipid comprises lethicin.  
   
   
       67 . A therapeutic device, comprising a pressurized can, equipped with a metered dose valve and an actuator capable of dispensing a foam, and containing an oleaginous foam composition according to  claim 1  or  claim 36 .  
   
   
       68 . The device of  claim 67 , wherein the metered dose valve provides a unit dose of between about 10 μL and about 1000 μL.  
   
   
       69 . The device of  claim 67 , wherein the metered dose valve provides a unit dose of between about 50 μL and about 250 μL.