The present invention is related to a foamable composition of matter comprising iodine, water, a foam adjuvant, a surface-active agent and a gelling agent. This foamable composition, which may be provided in a propellant free foaming device, or alternatively may further comprise a propellant, evolves into foam, which is effective in the topical treatment and prevention of various skin disorders.

Description of the Invention

SUMMARY OF THE INVENTION

The present invention provides a foamable composition including iodine, water, a foam adjuvant, a surface-active agent and a gelling agent that is easily applied and provides high availability of iodine to the applied surface.

According to one aspect the present invention, a foamable composition includes iodine, water, a foam adjuvant, a surface active agent and a gelling agent, in the following concentrations: about 0.1% to about 5% by weight iodine; about 80% to about 99.6% by weight of at least one solvent; about 0.1% to about 5% by weight of at least one foam adjuvant; about 0.1% to about 5% by weight of at least one surface active agent; and about 0.1% to about 5% by weight of at least one gelling agent. The % values presented herein are provided on a weight (w/w) basis of the total composition.

The composition according to one or more embodiments of the present invention, when provided in a suitable foaming device, forms a foam that is effective in the topical treatment of various skin conditions.

According to one or more embodiments of the present invention, the composition is provided in a plastic or glass propellant free foaming dispenser and forms a breakable or collapsible foam when dispensed from the propellant free foaming dispenser.

According to one or more embodiments of the present invention, the composition further includes a liquefied or compressed gas propellant, for example, at a concentration of about 3% to about 25% of the total composition.

According to one or more embodiments of the present invention, the foamed composition has specific gravity of about 0.02 gr/ml to about 0.35 gr/ml.

According to one or more embodiments of the present invention, iodine is selected from molecular iodine and complexed iodine. Complexed iodine may be selected from cadexomer-iodine, diiodhydrin, domiodol, hydriodic acid, iodinated glycerol, iodoform, iodide and povidone-iodine

According to one or more embodiments of the present invention, the solvent is water or a water miscible organic solvent, such as a polyhydroxy compounds and poly-ethoxylated compounds. In one embodiment the composition has a water-to-water miscible organic solvent ratio of about 1:10 to about 10:1. Due to the skin irritability of lower alkyl alcohols, the water miscible compound is not a lower alkyl, e.g., C.sub.1-C.sub.5, alcohol.

In one or more embodiments, the polyhydroxy compound is selected from ethylene glycol, propylene glycol, glycerol, butanediols and isomers thereof, pentaerythritol, sorbitol, mannitol, dimethyl isosorbide, polyethylene glycol, polypropylene glycol, diethylene glycol monoethyl ether and mixtures thereof.

In one or more embodiments, the poly-ethoxylated compound is selected from polyethylene glycol, tetrahydrofurfuryl alcohol and polyethyleneglycol. The solvent can be mixtures of water, polyhydroxy compounds and/or poly-ethyoxylated compounds.

According to one or more embodiments, a surface active agent may be an anionic surface active agent, a cationic surface active agent, a nonionic surface active agent, a zwitterionic surface active agent, an amphoteric surface active agent, an ampholytic surface active agent and mixtures thereof.

In one or more embodiments, the surface-active agent includes at least a non-ionic agent. In one or more embodiments, the surface active agent is a mixture of a non-ionic surface active agent and an anionic surface active agent provided at a weight ratio of about 4:1 to about 1:4 more preferably a weight ratio of about 2:1 to about 1:2. In one or more embodiments, the surface-active agent has a HLB value higher than about 8.

According to one or more embodiments, the foam adjuvant is selected from a fatty alcohol, a fatty acid mixtures thereof, and is provided at a concentration between about 0.4% and about 2.5% of the composition.

Another aspect the present invention provides a method of treating, alleviating or preventing a human or veterinary disorder by topically administering to a surface afflicted with the disorder an effective amount of the composition according to one or more embodiments of the present invention.

The method of the invention, according to one or more embodiments, provides for the prophylaxis, or treatment of or alleviation of the symptoms of a variety of infectious dermatological disorders, including for example heat burns, chemical burns, infections, wounds, cuts and ulcers and radioactive radiation damage, and burns and infections resulting from chemical and biological warfare agents.

DETAILED DESCRIPTION OF THE INVENTION

Composition

According to one aspect, the present invention provides a foamable composition of matter includes iodine, water, a foam adjuvant, a surface active agent and a gelling agent, in the following concentrations, reported as percent by weight: iodine: about 0.1% to about 5%; at least one solvent: about 80% to about 99.6%; at least one foam adjuvant: about 0.1% to about 5%; at least one surface active agent: about 0.1% to about 5%; and at least one gelling agent: about 0.1% to about 5%. The % values presented herein are provided on a weight (w/w) basis of the total composition.

The composition according to one or more embodiments of the present invention is applied to the surface as a foam. That is, the foamed composition is applied to the substrate and is not generated by rubbing or lathering. The foamed composition, according to one or more embodiments of the present invention, is dispensed from a glass or plastic container that dispenses foam in the absence of a gas or liquid propellant.

Alternatively, the composition of the present invention further includes a liquefied or compressed gas propellant at a concentration of about 3% to about 25% of the total composition. Examples of suitable propellants include volatile hydrocarbons such as butane, propane, isobutane or mixtures thereof, and fluorocarbon gases.

The foamed composition, according to one or more embodiments of the present invention, is of exceptionally low specific gravity, for example, the foamed composition has a specific gravity in the range of about 0.02 gr/ml to about 0.35 gr/ml. Although of low specific gravity, the foam is highly stable and will remain without collapse for several minutes. Nonetheless, the foam collapses readily upon application of mild shear stress. Low specific gravity, high foam stability and ready collapsibility all contribute to a foamed composition that is easily applied and administered over large areas without rubbing or chaffing of the affected area.

Iodine

"Iodine" and "iodine species" include iodine in its native form or released from a compound. In its native form, iodine (I.sub.2) is provided as bluish-black crystals, having density of about 5 g/cm.sup.3. When used as is, the iodine concentration in the total composition ranges between 0.1% and 5% and more preferably, between 0.5% and 1.5%. In other embodiments of the present invention molecular iodine is released from an iodine-containing and/or producing compound. Non-limiting examples of such compounds include cadexomer-iodine, diiodhydrin, domiodol, hydriodic acid, iodinated glycerol, iodide, iodoform, and povidone-iodine. When provided as an iodine-containing and/or producing compound, the compound concentration in the total composition is calculated to achieve a final iodine concentration ranging between about 0.1% and 5% by weight and more preferably, between about 0.5% and about 1.5% by weight.

Solvent

According to one or more embodiments, the composition includes about 80% to about 99.6% solvent, and typically includes water. Iodine is not highly soluble in water and thus, formulation stability and effectiveness is limited. In a one or more embodiments of the present invention, the solvent includes water and a water miscible organic solvent, which by way of non-limiting examples, is a polyhydroxy compound and/or a poly-ethoxylated compound.

Suitable polyhydroxy solvents (polyols) include small organic molecules having two or more hydroxy groups on their carbon skeleton, such as ethylene glycol, propylene glycol, glycerol, butanediols and isomers thereof, pentaerythritol, sorbitol, mannitol, dimethyl isosorbide, polyethylene glycol, polypropylene glycol, diethylene glycol monoethyl ether (Transcutol.RTM.) and mixtures thereof.

Poly-ethoxylated compounds can enhance the effectiveness of iodine significantly by dissolving the I.sub.2. Examples of suitable poly-ethoxylated compounds include polyethylene glycol (e.g., PEG 400), tetrahydrofurfuryl alcohol polyethyleneglycol ether (glycofurol, tetraglycol (TG)). Among the above-mentioned water miscible solvents, suitable compounds include transcutol, polyethylene glycol and TG and mixtures thereof. The ratio between water and the water miscible solvents is in the range of about 1:10 to about 10:1. In one or more embodiments, the ratio is between about 1:4 and about 4:1. Due to the skin irritability of lower alkyl (C1-C5) alcohols, and the tendency of such alcohols to impair the natural skin barrier by dissolving and removing the oily components of the skin, lower alkyl alcohols are not included as a miscible organic solvent.

Foam Adjuvant

A foam adjuvant is included in the composition to improve the stability and reduce the specific gravity of the foamed composition. In one or more embodiments of the present invention, foam adjuvants include fatty alcohols, fatty acids, and mixtures thereof. The foam adjuvant can include at least one fatty alcohol and at least one fatty acid.

Suitable fatty alcohols include alcohols having 15 or more carbons in their carbon chain, such as cetyl alcohol and stearyl alcohol (or mixtures thereof). Other examples of fatty alcohols are arachidyl alcohol (C20), behenyl alcohol (C22), 1-triacontanol (C30), as well as alcohols with longer carbon chains (up to C50). The concentration of the fatty alcohol required to support the foam system is inversely related to the length of its carbon chains. Fatty alcohols that are derived from beeswax, including a mixture of alcohols, a majority of which has at least 20 carbon atoms in their carbon chain, are especially well suited as foam adjuvants according to the present invention. The concentration of the fatty alcohol required to support the foam system is inversely related to the length of its carbon chains.

Suitable fatty acids include acids having 16 or more carbons in its carbon chain, such as hexadecanoic acid (C16) stearic acid (C18), arachidic acid (C20), behenic acid (C22), octacosanoic acid (C28), as well as fatty acids with longer carbon chains (up to C50), or mixtures thereof. As for fatty alcohols, the concentration of fatty acids required to support the foam system is inversely proportionate to carbon chain length.

Optionally, the carbon atom chain of the fatty alcohol or the fatty acid may have at least one double bond. A further class of foam adjuvant agent includes a long chain fatty alcohol or fatty acid, wherein the carbon atom chain is branched. The carbon chain of the fatty acid or fatty alcohol can be substituted with a hydroxyl group, such as 12-hydroxy stearic acid.

The foam adjuvant of the present invention may include a mixture of fatty alcohols, fatty acids and hydroxy fatty acids and alcohols in any proportion. The total amount of foam adjuvants is about 0.1% to about 5% (w/w) of the carrier mass, and typically, the total amount is about 0.4% to about 2.5% (w/w) of the carrier mass.

In one or more embodiments of the present invention, a fatty alcohol possesses a therapeutic properties per se. Long chain saturated and mono unsaturated fatty alcohols, e.g., stearyl alcohol, erycyl alcohol, arachidyl alcohol and docosanol have been reported to possess antiviral, anti infective, anti-proliferative and anti-inflammatory properties (U.S. Pat. No. 4,874,794). Longer chain fatty alcohols, e.g., tetracosanol, hexacosanol, heptacosanol, octacosanol, triacontanol, etc. are also known for their metabolism modifying properties and tissue energizing properties. Long chain fatty acids have also been reported to possess anti-infective characteristics. Thus, the iodine foamable composition of the present invention, containing the foam adjuvant provides a synergistic therapeutic benefit in comparison with currently used vehicles, which are inert and non-active.

Surface-active Agent

According to one or more embodiments of the present invention, the surface-active agent includes any agent linking oil and water in the composition, e.g., the agent can be a surfactant. In one or more embodiments of the present invention, the composition includes about 0.1% to about 5% of the surface-active agent.

Suitable surface-active agents include anionic, cationic, nonionic, zwitterionic, amphoteric and ampholytic surfactants, as well as mixtures of these surfactants. Such surfactants are well known to those skilled in the pharmaceutical and cosmetic formulation art. Non-limiting examples of useful surfactants include sucrose esters, sorbitan esters, PEG esters or ethers of fatty chains, mono or diglycerides, isoceteth-20, sodium methyl cocoyl taurate, sodium methyl oleoyl taurate, sodium lauryl sulfate, triethanolamine lauryl sulfate and betaines (e.g., cocamidopropyl betaine and lauramidopropyl betaine), which are known to contribute to foam stability (foam boosters).

While any surface-active agent may be used in the present invention, a surface-active agent having an HLB (hydrophilic-lipophilic balance) higher than 8 is used in one or more embodiments of the present invention.

Non-ionic surfactants are particularly well suited as surface-active agents. A combination of a non-ionic surfactant and an anionic surfactant (such as sodium lauryl sulfate) may also be used. A ratio of non-ionic surfactant to anionic surfactant between around 4:1 and about 1:4, or between about 2:1 and about 1:2, provides a foam, which upon rubbing onto the skin collapses easily, to allow facile spreading and absorption. A surface-active agent mix is even further improved when a foam stabilizing surfactant, such as cocamidopropyl betaine, is added.

Gelling Agent

In one or more embodiments of the present invention, the composition includes about 0.1% to about 5% of a gelling agent. Suitable gelling agents include, in a non-limiting manner, naturally-occurring polymeric materials such as locust bean gum, guar gum, sodium alginate, sodium caseinate, egg albumin, gelatin agar, carrageenin gum, sodium alginate, xanthan gum, quince seed extract, tragacanth gum, starch, chemically modified starches and the like, semi-synthetic polymeric materials such as cellulose ethers (e.g. hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, hydroxy propylmethyl cellulose), hydroxypropyl guar gum, soluble starch, cationic celluloses, cationic guars and the like and synthetic polymeric materials such as carboxyvinyl polymers, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid polymers, polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidene chloride polymers and the like.

Also useful herein are gelling agents such as the acrylic acid/ethyl acrylate copolymers and the carboxyvinyl polymers sold, for example, by the B.F. Goodrich Company under the trademark of Carbopol.RTM. resins. These resins include a colloidal water-soluble polyalkenyl polyether cross linked polymer of acrylic acid cross linked with from 0.75% to 2% of a cross linking agent such as polyallyl sucrose or polyallyl pentaerythritol. Examples include Carbopol 934, Carbopol 940, Carbopol 950, Carbopol 980, Carbopol 951 and Carbopol 981. Carbopol 934 is a water-soluble polymer of acrylic acid cross linked with about 1% of polyallyl ether of sucrose having an average of about 5.8 allyl groups for each sucrose molecule.

Methods of Evolving and Releasing the Foam

Any customary method of evolving foam is applicable according to the present invention. By way of example, in one optional configuration, the composition according to one or more embodiments of the present invention is preferably placed, together with a liquefied or compressed gas propellant in the amount of about 3% to about 25% of the total composition, in an aerosol container. Upon pressing the actuator, a breakable foam, suitable for topical administration is released. Due to the oxidizing nature of iodine, containers that are coated with highly durable lacquers of coatings are used.

In an alternative exemplary configuration, the composition according to one or more embodiments of the present invention is placed in a plastic or glass container, equipped with a foaming dispenser that works without gas propellants. Such dispensers are described, for example, in U.S. Pat. No. 6,536,629, in which the dispenser includes a container and a dispensing assembly coupled in liquid-tight manner. The dispensing assembly can have a liquid pump with a liquid inlet and a liquid outlet. An exemplary foam dispenser is shown in the FIGURE (see Original Patent).

Foam Characteristics

The foam that is released from the aerosol container or from the propellant-free foaming dispenser is well aerated. It has specific gravity of about 0.02 gr/ml to about 0.35 gr/ml. When applied onto a surface, specifically a skin surface, and rubbed gently, it spreads easily over the area, without the need of extensive rubbing.

A foam composition of one or more embodiments of the present invention is advantageous over formulation options. A foamed composition may possess one or more of the following properties. The foam is lightweight and thus, economical. The foam is easily spreadable, allowing treatment of large areas such as the arms, back, legs and the breast. The flow properties provide a foam that spreads effectively into folds and wrinkles, providing uniform distribution of the active agent without the need of extensive rubbing and absorbs into the skin. The low specific gravity, e.g., fluffy, nature of the foam renders application of the foam on large skin areas very easy, irritation-free and painless.

Foam Applications

The compositions according to one or more embodiments of the present invention are useful in the various medicinal disciplines including human and veterinary medicine. More generally, the compositions according to the present invention can be used in situations where use of iodine is preferred including, but not limited to, medicine, industrial processes, diagnostics and environmental purposes.

Specifically, the compositions according to one or more embodiments of the present invention are useful as antiseptic compositions. The compositions may be further used to protect from, prevent, alleviate the symptoms of or cure a variety of infectious dermatological disorders, including: bacterial Infections including cellulitis, acute lymphangitis, lymphadenitis, erysipelas, cutaneous abscesses, necrotizing subcutaneous infections, staphylococcal scalded skin syndrome, folliculitis, furuncles, hidradenitis suppurativa, carbuncles, paronychial infections, erythrasma; fungal infections including dermatophyte infections, yeast infections; parasitic infections including scabies, pediculosis, creeping eruption and viral infections.

The treatment of heat burns, chemical burns (caused by chemicals such as acids, bases, caustic materials and warfare chemicals), wounds, cuts and ulcers using the composition according to one or more embodiments of the present invention is particularly advantageous. Upon application, the foam spreads easily, covering the surface of the affected area, and without causing pain.

The composition of the invention is also useful as a protectant in case of exposure to radiation and radioactive isotopes.

According to another aspect the present invention provides a method of treating, alleviating or preventing a human or veterinary disorder by topically administering to a surface afflicted with the disorder an effective amount of the composition including: about 0.1% to about 5% by weight iodine; about 80% to about 99.6% by weight of at least one solvent; about 0.1% to about 5% by weight of at least one foam adjuvant; about 0.1% to about 5% by weight of at least one surface active agent; and about 0.1% to about 5% by weight of at least one gelling agent. The present invention provides for the prophylaxis, or treatment of or alleviating the symptoms of a variety of infectious dermatological disorders, including heat burns, chemical burns, infections, wounds, cuts and ulcers and radioactive radiation damage, and burns and infections resulting from chemical and biological warfare agents.
 

Claim 1 of 25 Claims

1. A foamable composition comprising a. about 0.1% to about 5% by weight iodine; b. about 80% to about 99.6% by weight of at least one solvent; c. about 0.1% to about 5% by weight of at least one foam adjuvant comprising at least one fatty alcohol, at least one fatty acid, or a mixture thereof; and d. about 0.1% to about 5% by weight of at least one surface active agent; and e. a liquefied or compressed gas propellant, wherein the weight ratio of the propellant to the remainder of the composition is about 3:97 to about 25.75, said composition housed in a pressurized container comprising a valve configured to release said composition as breakable foam.

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