Skin-moistening local disinfectant

Abstract

The present invention relates generally to a skin moisturizing topical material composition containing molecular iodine which is effective for vapor pressure reduction. In particular embodiments, the composition reduces the loss of molecular iodine to the atmosphere under storage conditions after administration to mammalian tissue.

Description

[0001] The present application is a divisional application of Chinese invention patent application No. 201780054315.6, filed on July 19, 2017, with the invention name “Moisturizing Local Disinfectant”, which is based on international application PCT / US2017 / 042726 and claims the priority of U.S. patent application No. 62 / 365,035 filed on July 21, 2016, which is incorporated herein by reference in its entirety. Technical Field

[0002] The present invention generally relates to an emollient topical composition containing molecular iodine having a reduced effective vapor pressure. In a specific embodiment, the composition reduces the loss of molecular iodine to the atmosphere under storage conditions after application to mammalian tissue. Background Art

[0003] Antibiotic resistance is a worldwide problem. New forms of antibiotic resistance can cross international borders and can spread easily between continents, many with remarkable speed. The CDC states that every year in the United States, at least 2 million people develop serious bacterial infections that are resistant to one or more of the antibiotics designed to treat those infections. At least 23,000 people die each year in the United States due to these antibiotic-resistant infections. Many more die from other illnesses that are concurrent with their antibiotic-resistant infections.

[0004] Antibiotic-resistant infections add considerable and avoidable costs to the already overburdened U.S. healthcare system. In most cases, antibiotic-resistant infections require prolonged and / or more expensive treatment, prolong hospital stays, require additional physician visits and healthcare use, and result in greater disability and death compared to infections that are easily treated with antibiotics. Estimates of the overall economic costs of antibiotic resistance to the U.S. economy vary but range from as high as $20 billion in direct healthcare costs to as much as $35 billion per year in additional costs to society due to lost productivity.

[0005] Antibiotic use is the single most important factor contributing to antibiotic resistance worldwide. Antibiotics are the most commonly prescribed drugs in human medicine. However, up to 50% of all antibiotics prescribed to people are either not needed or do not work as optimally as prescribed, depending on the prescription. Antibiotics are also commonly used in food for animals to prevent, control and treat disease, and to promote growth in animals that produce food, thus complicating the problem.

[0006] Staphylococcus aureus (S. aureus) is the leading cause of surgical site infections, with approximately 80% of S. aureus infections caused by the patient's own nasal flora. Methicillin-resistant S. aureus (MRSA) is the most common causative pathogen in acute bacterial skin and skin structure infections (ABSSSI) treated in hospitals. MRSA currently kills more people each year than AIDS and HIV combined.

[0007] Molecular iodine has been shown to be very effective against MRSA and has the advantage of being a broad-spectrum antimicrobial nasal agent with extensive in vitro and in vivo evidence. Molecular iodine's activity is effective against both common bacteria and antibiotic-resistant species. Molecular iodine does not produce resistant bacterial strains.

[0008] Eliminating local pathogens including bacteria, viruses and fungi from mammals is an established preventive and therapeutic approach in health and medicine. Many topical compositions, intravenous (IV) treatments, devices and clinical procedures are used daily to eliminate local pathogens in an attempt to improve patient outcomes. However, nasally transmitted Staphylococcus aureus (MRSA) has not been effectively addressed.

[0009] About one-third (33%) of people carry Staphylococcus aureus in their noses (http: / / www.cdc.gov / mrsa / tracking), and two in 100 people carry MRSA. In a study of patients who were once identified as MRSA carriers, 91% of patients were MRSA positive in nasal samples, and nearly 25% of them had MRSA in the nasal cavity, but not in other parts of the body (Antimicrob.Agents Chemother. November 2007, Vol. 51, No. 11, 3880-3886). The only treatment approved for eliminating MRSA from nasal colonies is BactrobanTM, and its active agent is the antibiotic mupirocin. The percentage of Staphylococcus aureus observed in patients resistant to mupirocin in 2002 was estimated to be about 18% (Antimicrob.Agents Chemother. November 2007, Vol. 51, No. 11, 3880-3886). Therefore, increasing the use of antibiotics to eliminate nasally transmitted MRSA is a suboptimal long-term strategy.

[0010] Iodine-based preparations are used for disinfection of epidermal tissues in many clinical situations, e.g., prior to surgery, catheterization, burns, needle sticks, wound care, or topical infections. These iodine-based preparations are entirely dependent on the biocidal activity of molecular iodine (Hickey et al., J Pharm Pharmacol. 1997 Dec;49(12):1195-9). In fact, bacteria can survive for long periods of time in a 10% polyvinylpyrrolidone-iodine ("PVP-I") formulation if the molecular iodine is highly complexed so that the effective concentration of molecular iodine is less than 1 ppm. (Favero MS, Infect. Control, 1982 Jan-Feb;3(1):30-2). Simply adding molecular iodine to an aqueous preparation is not sufficient to ensure its presence in the preparation, because once the molecular iodine undergoes hydrolysis, other iodine species are formed, such as iodide, hypoiodous acid, iodide, triiodide, iodate.

[0011] Almost all topical iodine compositions taught in the literature are based on iodophors (any of a group of disinfectants containing triiodide in combination with a surfactant and not in balance with iodide and trace molecular iodine) or formulations in which molecular iodine is complexed with iodide. These additional iodine species (iodide, triiodide, and PVP-I) increase the potential risk of systemic toxicity and promote staining, but do not have antimicrobial activity (they are included to stabilize molecular iodine). The view that iodophors can reduce the staining and negative sensory properties of molecular iodine is not supported by the data and is inconsistent with published data, although this may be true for the Lugols Solution. See, for example, Duan Y et al., J Hosp Infect. November 1999, 43(3): 219-29; U.S. Patent No. 6,432,426; and U.S. Patent No. 6,261,577.

[0012] Since the development of PVP-I, many topical iodine-based formulations have been proposed in the art. For example, U.S. Patent No. 9,114,156 and U.S. Patent No. 6,228,354 describe thin film-forming polymers containing PVP-I. U.S. Patent No. 7,147,873 teaches a thin film-forming polymer containing molecular iodine and an iodophor. U.S. Patent No. 8,808,722 describes a complex iodine formulation formed from a molecular iodine / iodophor combination containing titratable iodine at a concentration of 0.1% to 2% and an iodine salt present at a minimum concentration of 2.0% by weight.

[0013] US Patent No. 8,840,932 teaches a film-forming antimicrobial composition containing molecular iodine and PVP-I, but molecular iodine is not included as an ingredient in any of the examples of the application, nor are conditions described for providing a stable environment for molecular iodine in the absence of PVP-I.

[0014] U.S. Patent No. 5,922,314 teaches an antimicrobial film-forming composition comprising ethanol, carboxylated polyacrylate, a crosslinker, an adhesion promoter, an active antimicrobial agent which may be iodine or PVP-I, a complex polyol, and molecular iodine and / or PVP-I. This '341 patent teaches increased stability of "iodine" but does not teach conditions for stabilizing molecular iodine in an aqueous environment. In fact, Example 1 demonstrates a lack of molecular iodine stability in the absence of 10% PVP-I. Specifically, when included in the disclosed formulation of Composition A of this example (which contains only molecular iodine), the formulation exhibits almost a 50% loss of iodine compared to a composition containing 10% PVP-I; the 50% loss of available iodine is comparable to the control.

[0015] In U.S. Patent No. 5,370,815 and U.S. Patent No. 5,227,161, effective formulation methods for providing local antimicrobial compositions of pure molecular iodine in enzyme-based formulations are taught. U.S. Publication No. 20060280809 (abandoned), U.S. Patent No. 5,897,872 and PCT Publication No. WO2012177251 teach the use of PVP-I in the sinus cavity to treat sinusitis. U.S. Patent No. 8,303,994 and U.S. Patent No. 8,691,290 teach methods for killing pathogens residing in the nasal cavity based on molecular iodine produced by the reaction of iodide with iodate, so that the final concentration range is 25 ppm-about 250 ppm. Summary of the invention

[0016] The present invention relates to compositions containing molecular iodine for tissue disinfection. The compositions taught herein can be used to treat epidermal and mucosal tissues (including oral tissues, nasal passages including the anterior nares, esophagus and vagina) prior to invasive procedures and to eliminate pathogens that have caused or have the potential to cause morbidity and / or mortality.

[0017] More specifically, the present invention relates to pharmaceutically acceptable formulations based on emollient organic carrier molecules which: (1) have a vapor pressure at standard atmospheric pressure that is at least 30% lower than the vapor pressure of molecular iodine; (2) have a boiling point at standard atmospheric pressure that is greater than 100°C; and (3) provide an environment that stabilizes molecular iodine for at least nine (9) months at room temperature.

[0018] Iodine-based topical antimicrobial agents are widely used clinically. Molecular iodine is the only biocide in iodophor preparations, has a low vapor pressure, and is rapidly lost to the atmosphere when dissolved in an aqueous preparation exposed to the atmosphere. Iodophors stabilize low levels of unbound (free) molecular iodine to inactivate pathogens by maintaining a reservoir of bound molecular iodine in the form of triiodide in equilibrium with molecular iodine, where the relative concentrations of these two substances (triiodide / molecular iodine) are on the order of 10,000 to 1.

[0019] Once the iodine tincture is diffused into mammalian tissue, the surface area to volume ratio of the applied iodine tincture is very high. This high surface area to volume ratio ensures that any free molecular iodine is lost to the atmosphere very quickly. Film-forming iodine tinctures that claim to provide a durable antimicrobial barrier have been developed. However, once a film is formed by the iodine tincture, there is no free molecular iodine. In these cases, the free molecular iodine has either: (a) lost to the atmosphere, or (b) become solid due to the limited solubility of molecular iodine, and then sublimated into the atmosphere. Before the film formed with the iodine tincture can provide antimicrobial activity, it must be redissolved, possibly by wound exudate. As a result, the composition must have a very high concentration of iodine tincture, which can inhibit the release of free molecular iodine.

[0020] In various embodiments, provided herein are topical iodine-based compositions that: (a) deliver free molecular iodine at concentrations 10 to 400 times higher than those in typical iodine tinctures, (b) are emollient; and (c) reduce the effective vapor pressure of molecular iodine such that the molecular iodine is retained in the composition upon exposure to the atmosphere at least an order of magnitude longer than a comparable aqueous composition.

[0021] In various embodiments, the compositions contemplated herein are effective in providing topical compositions that can maintain high concentrations of free molecular iodine in contact with mammalian tissue for extended periods of time, as compared to iodophors. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figures 1A-1C The results of Example 4 according to one embodiment of the present invention are shown.

[0024] Figure 2A-2L The results of Example 5 according to one embodiment of the present invention are shown, wherein Figure 2A-2L Respectively represent the photos of starch paper taken at 0 minute, 5 minutes, 20 minutes, 40 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 24 hours, and 48 hours.

[0025] Figure 3A and 3B The results of Example 6 according to one embodiment of the present invention are shown.

[0026] Figures 4A-4C The results of Example 7 according to one embodiment of the present invention are shown. DETAILED DESCRIPTION

[0027] The present invention will be described more fully below. However, the present invention can be implemented in many different forms and should not be interpreted as being limited to the embodiments set forth herein; on the contrary, these embodiments are provided to make this disclosure thorough and complete and to fully convey the scope of the present invention to those skilled in the art.

[0028] Unless otherwise indicated, all publications, patents, and patent applications cited herein, whether supra or infra, are incorporated herein by reference in their entirety. In the case of a publication, patent, or patent application incorporated herein by reference and the present disclosure defining the same term, the definition in the present disclosure shall prevail. For publications, patents, and patent applications cited for descriptions of specific types of compounds, chemistries, etc., the portions of the document relating to these compounds, chemistries, etc. are those portions of the document incorporated herein by reference.

[0029] To more conveniently understand the present invention and its preferred embodiments, the meanings of the terms used herein will become apparent from the context of this specification, combined with the common usage of the various terms and the explicit definitions of other terms provided in the following glossary or in the specification.

[0030] Glossary

[0031] It should be noted that, as used in this specification, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to a "gelling agent" refers to a single gelling agent as well as several different gelling agents, reference to an "excipient" includes a single excipient as well as two or more different excipients, etc.

[0032] "Optional" or "optionally" means that the subsequently described event may or may not occur, so that the description includes instances where said event occurs and instances where it does not.

[0033] The term "pharmaceutically acceptable" with respect to an entity or ingredient refers to an entity or ingredient that, at a specified level or, where no level is specified, has no significant adverse toxic effects on patients at a level known to be acceptable to those skilled in the art. All ingredients described in this application are pharmaceutically acceptable.

[0034] The term "molecular iodine" refers to diatomic iodine, which is represented by the chemical symbol I 2 (CAS Registry Number: 7553-56-2), whether dissolved, suspended or solid. When in the solid state, molecular iodine is also known as "elemental iodine".

[0035] The term "iodide" or "iodide anion" refers to the species represented by the chemical symbol I- (CAS Registry Number: 20461-54-5). Suitable counterions for the iodide anion include sodium, potassium, calcium, and the like.

[0036] The term "iodate" refers to the negatively charged iodate anion, represented by the chemical symbol IO 3 Commonly available iodates are suitable sources of iodate for use in the present invention and include, for example, sodium iodate (EC number: 231-672-5), potassium iodate (EC number: 231-831-9), and calcium iodate (EC number: 232-191-3), whether dissolved or solid.

[0037] As used herein, the term "complexed iodine" or "bound iodine" refers to a mixture of molecular iodine with other chemicals that bind to the molecular iodine and render it incapable of killing pathogens. Complexing molecular iodine with other chemicals such as iodide and / or polyvinylpyrrolidone is a formulation strategy used to increase the stability of molecular iodine. Lugol's solution is the first widely used example of complexed iodine.

[0038] The term "iodine tincture" as used herein refers to a mixture of molecular iodine and a polymer that is used to reduce the level of free molecular iodine in solution. Polymers used to form iodine tinctures include polyvinyl pyrrolidone, copolymers of N-vinyl lactams, acrylates and acrylamides, various polyether glycols, including nonylphenol ethoxylates, etc., and combinations thereof. Povidone-iodine (PVP-I) is an iodine tincture that is currently the most commonly used form of complexed iodine.

[0039] The term "polymer" as used herein includes homopolymers and copolymers, and "copolymers" include polymers of any length (including oligomers) of two or more types of polymerizable monomers, thus including terpolymers, tetrapolymers, etc., which may include random copolymers, block copolymers or sequential copolymers.

[0040] The term "all iodine species" in a sample refers to the total iodine of all iodine-containing components in the sample, regardless of their form.

[0041] The term "ratio of molecular iodine to all iodine species in a sample" refers to the ratio of molecular iodine (I2) in a sample divided by the iodine concentration of all iodine species in the sample.

[0042] The term "organic carrier for molecular iodine" refers to a pharmaceutically acceptable organic molecule in which molecular iodine is soluble and does not interact with molecular iodine to change its structure, i.e., supports the stability of molecular iodine. Propylene glycol and glycerol are two most preferred organic carriers.

[0043] As used herein, the term "organic additive" refers to an organic molecule that may be included with an organic carrier for molecular iodine to add additional features. Such organic molecules include propylene glycol monomethyl ether acetate, amyl alcohol, ethyl acetate, butyl acetate, ethanol, dimethyl sulfoxide, 1-propanol, and 2-propanol.

[0044] The term "gelling agent" or "viscosity enhancing agent" refers to a pharmaceutically acceptable organic molecule that is used to increase the viscosity of a composition.

[0045] The term "body temperature" refers to the temperature of the surface of the mammalian tissue being treated. For example, the temperature of normal healthy skin is between 32°C and 34°C, and the temperature of the mucosal lining of the nose is between 32.5°C and 35°C, depending on the measurement location and the patient.

[0046] The term "reconstituted shelf life" refers to the amount of time that molecular iodine is within a desired range after activation / mixing in a biphasic or multiphasic formulation.

[0047] The term "shelf life" refers to the amount of time a product can be stored in suitable packaging under normal storage conditions and still provide at least 90% of the declared activity.

[0048] The term "effective amount" as used herein refers to the concentration of a component in a pharmaceutical formulation required to inactivate a pathogen of clinical interest. The exact amount will depend on many factors, such as the components and physical characteristics of the pharmaceutical formulation, the intended indication, the intended patient population, etc., and can be determined by a person skilled in the art based on the information or methods provided herein.

[0049] The term "contact time required for efficacy" is used herein to refer to the minimum amount of time required for a composition to be in contact with mammalian tissue to be clinically effective.

[0050] The term "patient" refers to a living organism that can be treated by administering an appropriate embodiment of the teachings encompassed by the present invention.

[0051] "Normal storage conditions" with respect to the compositions of the present invention are an environment with a temperature of 5-40°C, a humidity of 10-90%, a pressure of 1 atmosphere (ATM) and approximately 20% oxygen and 80% nitrogen.

[0052] The term "pH control agent" shall mean a chemical that controls the effective pH of a composition or a component of a composition. Suitable pH control agents include carbonates, phosphates and acetates, formates, succinates, such as calcium carbonate, potassium acetate, sodium succinate, and the like.

[0053] The term "dual chamber package" refers to a package that keeps the components of a formulation separate during storage. The dual chamber package combines all ingredients in a formulation before use. The term dual chamber package also refers to a package containing more than two chambers.

[0054] The terms "single phase" and "dual phase" refer to packaging configurations contemplated in this application for formulations consisting of a single component or two components that are mixed prior to use. The term dual phase also refers to formulations consisting of more than two phases.

[0055] For the sake of brevity, all patents and other references cited herein are incorporated by reference in their entirety.

[0056] The biocidal substance in iodine-based disinfectants is molecular iodine. Because molecular iodine is unstable in aqueous environments, formulators use iodophors to provide small concentrations of molecular iodine in equilibrium with very large concentrations of iodide / triiodide and organic molecules that bind molecular iodine or triiodide. This results in a formulation in which the active agent, molecular iodine, is present in a concentration that is typically less than 0.1% of the total iodine species. Iodophors containing molecular iodine concentrations below a critical level can become contaminated with bacteria and cause the spread of infection.

[0057] The active agent identified in this application is molecular iodine. The ratio of molecular iodine to all iodine species in the compositions described in this application is at least 80%, preferably at least 90%, and most preferably 100% of all iodine species. The source of molecular iodine in the products contemplated in this application is the dissolution of molecular iodine in an emollient organic carrier. One problem associated with formulating pure molecular iodine in a liquid is the tendency of molecular iodine to be lost to the atmosphere.

[0058] The only form of iodine that forms a gas at room temperature is molecular iodine. The vapor pressure of molecular iodine at 25°C is 0.3 mm and the vapor pressure at 38.7°C is 1 mm. At standard atmospheric pressure, up to 394 ppm of iodine can accumulate in a closed container at 25°C. Iodine vapor strongly irritates mucous membranes and adversely affects the upper and lower respiratory systems. Inhalation of iodine vapor can cause tearing, chest tightness, sore throat, increased pulmonary flow resistance, reduced ventilation rate, and headaches. Humans can work undisturbed at 0.1ppm; have difficulty working at 0.15-0.2ppm, and cannot tolerate concentrations of 0.3ppm or higher.

[0059] Severe eye irritation was observed after 2 minutes at a concentration of 1.63 ppm, and the minimum lethal atmospheric concentration for rats was 80 ppm for 1 hour. The permitted exposure limit is 0.1 ppm (NIOSH, OSHA), but the odor is not detectable until a level of about 0.9 ppm is reached, so irritation occurs before the odor is detected.

[0060] Two formulation strategies are described in this application that allow for the incorporation of high concentrations of molecular iodine into the compositions of matter contemplated in this application. The first strategy is to use a low vapor pressure non-aqueous organic carrier with a boiling point above 100°C to contain the molecular iodine. The hydrophobic environment of the organic carrier identified in this application has a higher affinity for molecular iodine than water; this lowers the effective vapor pressure of molecular iodine and reduces the loss of molecular iodine to the atmosphere.

[0061] A second strategy to reduce the vapor pressure of molecular iodine is to use cyclodextrins that do not neutralize molecular iodine but provide inclusion cavities from which molecular iodine cannot easily escape. The use of preferred cyclodextrins reduces the vapor pressure of molecular iodine as demonstrated in the examples contained in this application.

[0062] The preferred emollient organic carrier of the present application (a) has a gas phase less than 30% of the molecular iodine gas phase, and (b) boils at a temperature above 100°C. The preferred emollient organic carrier of the present application can dissolve at least twice as much molecular iodine per unit volume as water. The combination of these features can significantly reduce the rate of loss of molecular iodine to the atmosphere when applied to the epidermal surface compared to the loss in the aqueous composition. If it is desired to increase the release rate of molecular iodine from the composition for a specific use, the preferred emollient organic carrier of the present application can be mixed with water before application.

[0063] Preferred formulations identified in the present application use propylene glycol or glycerol as the emollient organic carrier for molecular iodine. Additional organic carriers may be included in the compositions contemplated in the present application to provide auxiliary product features. Other organic carriers that may be included in the compositions contemplated in the present application include propylene glycol monomethyl ether acetate, amyl alcohol, ethyl acetate, butyl acetate, dimethyl sulfoxide, 1-propanol and 2-propanol, dimethyl sulfoxide, ethanol, isopropanol, ethanol, etc.

[0064] Several different packaging configurations are contemplated in the present invention. In one configuration, the product will be contained in a single compartment. In another configuration, the product will be contained in two separate compartments that are mixed before being applied to the mammalian tissue of interest. In yet another configuration, the product will be contained in three different compartments or materials that are mixed or contacted with each other before being applied to the tissue of interest. These different packaging configurations increase the quantity of the different excipients that can be included in the formulation, because many excipients reduce the stability of molecular iodine to the point where it is impossible to achieve enough stability to place the product in commercial distribution, thereby the active agent will be lost.

[0065] The multi-compartment packaging allows the aqueous phase to be mixed with the organic carrier phase immediately prior to application of the topical compositions described herein. Water-soluble polymers, gelling agents, fragrances and pH control agents may be incorporated into this aqueous phase to impart desired formulation characteristics.

[0066] Other elements of the present invention include viscosity enhancers familiar to those skilled in the art, such as hydroxypropylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, poloxamers (copolymers of polyoxypropylene and polyoxyethylene), crosslinked homopolymers of acrylic acid such as Ultrez 30, carboxymethylcellulose or guar gum. Certain embodiments of the compositions described herein preferably have a viscosity of no greater than 100,000 centipoise (cps), more preferably no greater than 50,000 cps, even more preferably no greater than 10,000 cps, and most preferably no greater than 500 cps.

[0067] Another element of the present invention includes unsaturated fatty acids that impart long-lasting residual bactericidal activity. A representative list of these agents includes lactic acid, myristic acid, 1-monoure uridine, dodecanoic acid, and capric acid. Lactic acid and caproic acid can be incorporated directly into propylene glycol; the other unsaturated fatty acids must be incorporated into the aqueous phase, which is mixed with propylene glycol or glycerol prior to use.

[0068] Preferred compositions of the present invention are substantial in moist environments, such as the nose, anterior nares, and vaginal vaults, and remain on any of these tissues for longer periods of time than typical antimicrobial agents such as 10% povidone-iodine solution (Purdue Frederick, Norwalk, CT). A "substantial" composition is one that, when placed on mammalian tissue such as the anterior nares, still has some residual molecular iodine after killing most microorganisms (which occurs within a few minutes) after instillation of 0.25 milliliters (mL) with a cotton ball and gentle massage of the nostril for 30 seconds to ensure even distribution (as long as the patient does not expel or intentionally or accidentally wipe the product). In specific embodiments described herein, preferred substantial compositions remain in the anterior nares for 50 minutes, more preferably at least 60 minutes, after instillation.

[0069] The literature is replete with iodine phorbium compositions that form thin films to enhance their biocidal activity. The formulation approach inherent to film-based iodine phorbium is to provide a complex iodine phorbium composition that provides a very small concentration of molecular iodine that dries onto the skin surface and may have the ability to release some molecular iodine if the film interacts with a moist environment. It has been demonstrated that molecular iodine is absorbed by the skin and excreted from the skin for at least 24 hours. Furthermore, the concentration of molecular iodine absorbed and degassed is directly proportional to the concentration of the iodine applied to the skin. Certain topical applications contemplated in this application anticipate converting the skin into an active antimicrobial barrier by impregnating the molecular iodine into the skin, which is contrary to the approach taken by film-forming topical iodine phorbium formulations.

[0070] Some additives have been identified that allow molecular iodine to remain in the formulation for a period of time after administration necessary for efficacy and then induce dissipation of the molecular iodine by forming iodide.

[0071] A particularly important property of the antimicrobial composition of the present invention for use on skin, wounds or mucosal tissues is the ability to rapidly reduce the bacterial load on the tissue, particularly the skin (e.g., kill natural skin flora). In specific embodiments of the invention described herein, the composition is capable of reducing normal skin flora by at least 1 log (10-fold), more preferably at least 1.5 log, and most preferably at least 2 log.

[0072] The present invention overcomes the limitations of the prior art by providing an emollient composition containing high concentrations of substantially pure molecular iodine which can remain in contact with tissue for extended periods of time.

[0073] The following examples are provided to illustrate the teachings of the present application and are not intended to limit the present invention in any way.

[0074] Example

[0075] Example 1

[0076] Iodine crystals (Alfa Aesar; Ward Hill, MA; Catalog No. 14248; Lot No. 104Z003) were added to approximately 50 mL of propylene glycol in a screw cap vial to achieve a w / v (iodine / organic vehicle) ratio of 1 mg / mL.

[0077] A second screw cap vial was used to form a comparable molecular iodine solution in glycerol. A stirring bar was placed in the vial and the vial was sealed using a Teflon lined screw cap. Both vials were stirred at room temperature for 14 days. Aliquots from the two saturated solutions were diluted in their respective organic vehicles to a concentration that produced an optical density of about 1.0 at 290 nm.

[0078] Take out 3.0mL of each dilution of molecular iodine solution in equal parts regularly and place in disposable plastic cuvette (Brand7591 70). The cuvette is tightly covered with LDPE cover and then wrapped with Teflon (PTFE) tape to prevent molecular iodine from being lost to the atmosphere. UV-VIS scans are collected for each sample, and the absorbance at 290nm and 360nm is used to monitor the molecular iodine stability as a function of time. The samples are stored under ambient conditions.

[0079] 20 time points were taken over a 4 month time frame and the absorbance values ​​were averaged. Values ​​greater than or less than 2 standard deviations from the mean were discarded and the mean recalculated. A sample was considered unstable if there was a 10% loss from the initial value measured.

[0080] The data indicate that molecular iodine is stable in both organic carriers. For example, after 120 days, the loss of molecular iodine in propylene glycol was less than 6%, and the loss of molecular iodine in glycerol was less than 5%. The standard deviation of all data points obtained in propylene glycol corresponded to less than 2% of the initial optical density, and the equivalent measurement in glycerol was less than 1.7%.

[0081] Example 2

[0082] The iodine stability in different organic solvents was tested using the procedure described herein. Specifically, iodine crystals (Alfa Aesar 14248 Lot 104Z003) were added to the following solvents at a concentration of 1 mg / mL: USP glycerol (Signma-Aldrich, St. Louis, MO; Catalog No. G2289), propylene glycol (Sigma-Aldrich, St. Louis, MO; Catalog No. D1435), and ethanol (Sigma-Aldrich, St. Louis, MO; Catalog No. 792799-24X1PT).

[0083] Place a stirring rod in the bottle and cover the bottle. Stir the sample at room temperature for 7-14 days. The resulting saturated solution is left unfiltered.

[0084] Aliquots from the saturated solutions were diluted with their respective solvents to concentrations that produced OD peak heights of approximately 1.0 at wavelengths of 290 nm and 360 nm in a spectrophotometer.

[0085] 3 ml aliquots of DMSO and ethanol with added iodine as determined in the above steps were placed in clear ISO certified disposable plastic cuvettes (Brand 7591 70). The cuvettes were tightly covered with LDPE lids which were wrapped with Teflon (PTFE) tape.

[0086] The samples were stored in drawers under ambient conditions. Measurements were taken at different time points in a spectrophotometer. By the 60th day, the ethanol sample had lost more than 20% of the original molecular iodine as measured by the optical density at 290nm and 360nm. In contrast, glycerol, propylene glycol and dimethyl sulfoxide did not lose any molecular iodine at a time point exceeding 270 days.

[0087] Example 3

[0088] Iodine was dissolved in acetate buffer to produce a saturated solution. Specifically, iodine crystals (Alfa Aesar 14248 Lot 104Z003) were added to pH 4.5 acetate buffer at a concentration of 1 mg / mL. A stirring bar was placed in the bottle and the bottle was covered. The sample was stirred at room temperature for 7-14 days. The resulting saturated solution was not filtered.

[0089] Various concentrations of carboxymethylcellulose (Sigma Aldrich, StLoius, MO; catalog number: 419273-1006; batch number: MKBT6160V; CAS #9004-32-4), hydroxypropylmethylcellulose (Moieularrecipes.com; F50; X00096CD4N; Marina del Rey, CA), poloxamer-188 (Alfa Aesar, Ward Hill, MA; catalog number: J66087; batch number: W24A018; CAS #9003-11-6), and Carbopol Ultrez 30 (Lubrizol, Cleveland, OH, catalog number: CBP1118; batch number: 0101499333) were added to aliquots of acetate buffer containing molecular iodine prepared as described above. The final sample contained 5% CMC, 5% HPMC, 5% Poloxamer-188, and 0.5% Carbopol Ultrez 30. The resulting sample was placed in a spectrophotometer (Spectra Max Plus 384 UV-Vis Spectrophotomer; Molecular Devices, Sunnyvale, CA) to confirm that the optical density at 290 nm and A360 nm was approximately 1.0A.

[0090] Aliquots (3 ml) of each polymer formulation containing molecular iodine were placed in clear ISO certified disposable plastic cuvettes (Brand 7591 70). The cuvettes were tightly covered with LDPE lids, which were wrapped with Teflon (PTFE) tape and the samples were stored in a drawer under ambient conditions.

[0091] Optical density measurements were taken at 290 nm and 360 nm at various time points to measure the amount of molecular iodine retained in each sample. More than 90% of the molecular iodine was lost in the samples containing carboxymethylcellulose. More than 30% of the molecular iodine was lost in the samples containing hydroxypropyl methylcellulose. The sample containing 5% poloxamer-188 showed a 10% decrease in molecular iodine concentration within 6 hours and a decrease of more than 25% within 24 hours. Compared to other polymers, Carbopol Ultrez 30 is compatible with molecular iodine for more than 9 months. Although the absolute concentration of molecular iodine is initially reduced by about 25%, this loss is stabilized so that the polymer can be combined with molecular iodine for an extended period of time.

[0092] Example 4

[0093] α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin (γ-cyclodextrin, catalog number: C4892, Sigma Life Sciences, Lot SLBL4156V, CAS17465-86-0), methyl β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin

[0094] The following cyclodextrins were tested for compatibility with molecular iodine: α- (Catalog No. C4642, Sigma Life Sciences, Lot 2X SLBK4630V, CAS10016-20-3), β- (Catalog No. C4767, Sigma Life Sciences, Lot MKBV2085V, CAS 7585-39-9), γ- (Catalog No. C4892, Sigma Life Sciences, Lot SLBL4156V, CAS17465-86-0), methyl-β- (Catalog No. C4555, Sigma Life Sciences, Lot WXBC0745V, CAS128446-36-6) and hydroxypropyl-β-cyclodextrin (H107, Sigma Life Sciences, Lot WXBC0083V, CAS128446-35-5).

[0095] Solutions of these cyclodextrins were prepared in acetate buffer or propylene glycol (both containing molecular iodine as follows). The cyclodextrins were weighed and added to a vial. A saturated molecular iodine solution (Alfa Aesar 14248 Lot 104Z003) was then prepared in either: (a) 30 mM acetate buffer (pH 4.5); or (b) propylene glycol. The measured concentrations of iodine in these solutions were 112 ppm and 672 ppm, respectively.

[0096] Aliquots of each solution of the different cyclodextrins were added to the vials to a final cyclodextrin concentration of 50 mM. Control vials containing only a saturated solution of molecular iodine in acetate buffer or propylene glycol were also prepared. The screw cap of each vial was equipped with an iodine sensitive paper disc (Fluka #37215, Lot SZBF1310V) which fit tightly in the cap so that the paper was exposed to the atmosphere in the vial, which would react the paper with molecular iodine in the vapor phase.

[0097] At the following time points: one (1) hour; six (6) hours; and twenty-four (24) hours, check the color of the indicator paper on the inside of the screw cap and take a picture. These results are shown in Figures 1A-1C middle.

[0098] At 1 hour, the control sample of molecular iodine in acetate buffer was highly colored. At 6 hours, the same control sample was almost 100% black. The only change observed at 24 hours was discoloration of the paper, which may have been partially protected by the threads of the screw cap vial.

[0099] At 1 hour, there was little or no color on any of the cyclodextrin samples prepared in acetate buffer. At 6 hours, molecular iodine vapor was clearly detected in the samples of both β and γ cyclodextrins. At 24 hours, molecular iodine vapor was clearly detected in the hydroxypropyl-β-cyclodextrin sample, and the indicator paper in the samples of both β and γ cyclodextrin samples was darkly stained.

[0100] There was little or no color on the cyclodextrin samples prepared in propylene glycol at 1 hour and 6 hours. At 24 hours, molecular iodine vapor could be detected on the indicator paper in all cyclodextrin samples prepared in propylene glycol; however, the color intensity in the propylene glycol samples was significantly lower than that in the acetate samples.

[0101] The observed data indicate that α-cyclodextrin, methyl-β-cyclodextrin, and hydroxypropyl-β-cyclodextrin reduce the vapor pressure of molecular iodine in an aqueous environment. Therefore, these agents can be used to stabilize aqueous compositions of molecular iodine.

[0102] In this experiment, molecular iodine in propylene glycol and molecular iodine in acetate buffer were used as controls; the indicator paper in these two control samples was compared to determine the ability of propylene glycol to reduce the vapor pressure of molecular iodine.

[0103] Comparison of the strength of the indicator papers from these two samples shows that propylene glycol can reduce the vapor pressure of molecular iodine by at least two orders of magnitude.

[0104] An additional control of molecular iodine in glycerol (1,120 ppm) was also included in this experiment. The color intensity of the indicator paper for molecular iodine in glycerol was visually indistinguishable from that observed for propylene glycol.

[0105] Example 5

[0106] Alpha cyclodextrin (Catalog No. 4642, Sigma Life Sciences, Lot 2X SLBK4630V, CAS 10016-20-3), beta cyclodextrin (Catalog No. C4767, Sigma Life Sciences, Lot MKBV2085V, CAS 7585-39-9), gamma cyclodextrin (Catalog No. C4892, Sigma Life Sciences, Lot SLBL4156V, CAS 17465-86-0), methyl beta cyclodextrin, (Catalog No. C4555, Sigma Life Sciences, Lot WXBC0745V, CAS 128446-36-6), and 2-hydroxypropyl-beta-cyclodextrin (Catalog No. H107, Sigma Life Sciences, Lot WXBC0083V, CAS 128446-35-5) were weighed into vials.

[0107] Aliquots of saturated molecular iodine in propylene glycol or 0.1 M acetate buffer (pH 4.5) were added to the vials to give a final cyclodextrin concentration of 50 mM. The samples were gently vortexed to dissolve the cyclodextrin. Control vials were prepared consisting of saturated iodine in propylene glycol or 0.1 M acetate buffer at pH 4.5.

[0108] A saturated molecular iodine solution in glycerol was also prepared and included in this experiment. Analytical potassium iodide starch paper (Fluka #37215, Lot SZBF1310V) was cut into circles and placed inside the screw cap of the vial, the paper being held in place once the cap was screwed onto the vial.

[0109] Figure 2A-2L Photographs of starch paper taken at different time points are provided to record the color of the starch paper relative to the time of exposure to the atmosphere inside the vial. The operating assumption is that the color of the starch paper is proportional to the time of exposure to the molecular iodine concentration in the atmosphere inside the vial.

[0110] The concentration of molecular iodine in the atmosphere inside the vial is proportional to the vapor pressure of molecular iodine dissolved in the liquid phase. The vapor pressure of molecular iodine in pure acetate buffer is expected to be higher than in all other experimental conditions, i.e. the starch paper in the acetate vial is expected to change color faster than in the other experimental treatments. The data prove this to be correct.

[0111] Starch paper staining of the acetate-only vial was detectable as early as 5 min and continued to increase until 4 h, when the reagent in the starch paper was completely depleted.

[0112] It is noteworthy that the starch paper staining at 48 hours in the glycerol control and propylene glycol control experimental vials was less than or equal to that in the acetate control vials at 20 minutes. In other words, the "effective" relative vapor pressure of molecular iodine in these two solvents is about two orders of magnitude lower than that in water.

[0113] Cyclodextrins appear to reduce the vapor pressure of molecular iodine in an aqueous environment (i.e., acetate buffer), as evidenced by the lower color intensity of the cyclodextrin vials compared to the acetate control. However, some cyclodextrins are more effective in reducing the vapor pressure of molecular iodine. For example, α-cyclodextrin, methyl-β-cyclodextrin, and hydroxypropyl-β-cyclodextrin reduce the vapor pressure of molecular iodine in acetate buffer to the greatest extent. Surprisingly, of these three cyclodextrins, only α-cyclodextrin and methyl-β-cyclodextrin reduce the vapor pressure of molecular iodine by 2 orders of magnitude or more.

[0114] The concentration of molecular iodine was measured by titration at the beginning and end of these experiments to determine whether the reduction in starch paper color intensity was due to cyclodextrin-induced reduction of molecular iodine to iodide. For all cyclodextrins except γ-cyclodextrin, more than 65% of the molecular iodine initially measured at time 0 was present at 48 hours.

[0115] This is a very high initial molecular iodine concentration, as simply opening and closing the control vial resulted in a loss of approximately 70% of the molecular iodine in the acetate control vial. These observations demonstrate that α-cyclodextrin, β-cyclodextrin, methyl-β-cyclodextrin, and hydroxypropyl-β-cyclodextrin can be used to reduce the vapor pressure of molecular iodine in an aqueous environment, with α-cyclodextrin, methyl-β-cyclodextrin, and hydroxypropyl-β-cyclodextrin being particularly effective, and methyl-β-cyclodextrin and hydroxypropyl-β-cyclodextrin being the most effective.

[0116] A similar cyclodextrin-induced decrease in vapor pressure was not observed in propylene glycol, which can be attributed to the different partition coefficients of molecular iodine in water versus propylene glycol. To demonstrate the effectiveness of glycerol and propylene glycol in stabilizing molecular iodine, the levels of molecular iodine were measured by titration at the beginning and end of these experiments. Despite opening and closing the cap multiple times, a percentage of 96.6% of the original molecular iodine was detected in the glycerol sample at 48 hours, with the value for propylene glycol being 94.5%.

[0117] Example 6

[0118] Molecular iodine was dissolved in glycerol and propylene glycol and then tested to determine whether molecular iodine dissolved in these organic carriers could be used to inactivate a methicillin-resistant (MRSA) strain of Staphylococcus aureus (MRSA TCH1516).

[0119] Live MRSA TCH1516 was washed, centrifuged, resuspended, and 200uL of bacteria were streaked onto a standard method agar plate (Cole Palmer, Vernon Hills, IL: Item# EW-14201-44). The lid on the plate was removed and the plate was placed in a 37°C incubator with the bottom of the plate facing up to remove any residual moisture from the surface of the plate. The plate was kept in this position for more than one hour to "dry" the surface of the bacterial lawn.

[0120] Then take the plate out of the incubator, apply 20uL of the carrier with molecular iodine to the plate, put a lid on the agar plate, and return the plate to the incubator to culture until thick bacterial colonies appear.

[0121] like Figure 3A As shown, the plate receiving the propylene glycol carrier has a clear circle in its center where 20 uL of propylene glycol with 952 ppm molecular iodine was deposited. The size of the circle is significantly larger than the surface area covered by the 20 μL fluid volume, indicating that there is some diffusion. This clearly demonstrates the biocidal ability of the composition.

[0122] The same results were observed with the glycerol-iodine samples. Figure 3B As shown, the bacterial killing area in the glycerol case was less than that observed for the propylene glycol sample, but the concentration of molecular iodine in the glycerol sample (516 ppm) was approximately half that in the propylene glycol carrier.

[0123] Both of these examples demonstrate the ability of molecular iodine to inactivate pathogens when incorporated into the preferred organic carriers identified in this application.

[0124] Example 7

[0125] The rheological properties of compositions intended for nasal topical use are important formulation considerations. Once an antimicrobial agent is placed in the nasal cavity, its residence time can affect its ability to eliminate microorganisms present in the nasal cavity. Therefore, the present invention contemplates compositions of matter that include a viscosity enhancing agent.

[0126] Fluid viscosity is basically the momentum transfer resulting from collisions with other molecules. When thought of in this way, it is not surprising that a fluid exhibits different viscosities when in different states; ketchup is a familiar example of this, as the apparent viscosity required for it to initially flow is higher than the apparent viscosity required for the flow to continue.

[0127] Viscosity was measured using a Brookfield DV2T viscometer, which allows precise control of the temperature at which the viscosity is measured. The Brookfield DV2T was programmed to measure viscosity at different shear rates by systematically accelerating the spindle (CP-40 or CP-52) up and then down, as Figure 4AAs shown for propylene glycol at 25°C.

[0128] The viscosity measurements at each spindle speed are then plotted, as Figure 4B Propylene glycol behaves like a Newtonian fluid in that viscosity is largely independent of shear and is the same for increasing and decreasing shear. The viscosity values ​​were fit to a curve and extrapolated to the zero shear value to get a final estimate of viscosity.

[0129] The viscosity of propylene glycol at 25°C and 33°C was calculated to be 59 centipoise (cP) and 95 cP (centipoise). A temperature of 33°C was chosen as a representative thermal environment on the nasal lining. An existing commercial product (3M TM Skin and nasal antiseptic; Povidone-iodine solution 5% w / w [0.5% available iodine] USP) Patient preoperative skin preparation, catalog item 192401) viscosity was used as a viscosity control. 3M was measured at 25°C and 33°C TM The viscosity of the skin and nasal antibacterial products is shown in Table 1 below.

[0130] Table 1

[0131]

[0132] Several propylene glycol compositions containing Carbopol Ultrez 30 polymer (Lubrizol Company, Cleveland, OH) in propylene glycol were prepared with increasing concentrations of Ultrez 30 in PG: 0.1%, 0.2%, 0.3%, 0.4% and 0.5%.

[0133] A series of samples were prepared without molecular iodine and a second series of samples were prepared with 800 ppm molecular iodine. The viscosity of these samples was measured using the up and down rate ramp procedure as described above. The results were fit to an Ostwald model, i.e., a stress versus shear rate curve fit, and the consistency constant was reported as the viscosity. The basic data demonstrates the non-Newtonian viscosity of the Ultrez 30 samples. The results show a stepwise increase in viscosity with increasing Ultrez 30 concentration. Unexpectedly, as Figure 4C As shown, the Ultrez 30 viscosity curve is different for samples with or without iodine.

[0134] As shown in Table 2 below, the data demonstrates that Carbopol Ultrez 30 can be used to prepare formulations that provide a wide range of viscosities suitable for topical application to the nasal cavity and other mammalian surfaces.

[0135] Table 2

[0136] sample Temperature ℃ Viscosity 0.1% Carbopol Ultrez 30 in PG 33 59.9 0.2% Carbopol Ultrez 30 in PG 25 487 0.2% Carbopol Ultrez 30 in PG 33 374 0.3% Carbopol Ultrez 30 in PG 25 1082 0.3% Carbopol Ultrez 30 in PG 33 1137 0.4% Carbopol Ultrez 30 in PG 25 5123 0.4% Carbopol Ultrez 30 in PG 33 4996 0.5% Carbopol Ultrez 30 in PG 25 13370 0.5% Carbopol Ultrez 30 in PG 33 11197 1% Carbopol Ultrez 30 in PG 25 80012 1% Carbopol Ultrez 30 in PG 33 68963

[0137] Example 8

[0138] Healthy 10-12 week old Hsd:ICR mice weighing 25-30 g (female) or 30-35 g (male) were housed in cages containing 5 animals and provided with mouse chow and water ad libitum. Animals were randomly assigned to one of the three treatment regimens. All mice in a cage were assigned to the same treatment regimen. The treatment regimens were: (a) glycerol (negative control); (b) 3M TM Skin and nasal disinfectant; and (c) 400 ppm molecular iodine in glycerol. The experiment was repeated for three days.

[0139] The mice were challenged with a suspension (10uL) containing 10E8CFU / mL MRSA TCH1516) sucked into each nostril. Twenty-four hours later, one of the three treatments was applied to the nostrils (10 μL) of each mouse. 24 hours after the mice were treated, the mice were euthanized and their nasal cavities were isolated. The nasal cavities were vortexed vigorously (10 seconds, 3 times) in phosphate buffered saline (PBS), serially diluted in PBS and plated on Todd Hewitt agar (THA) plates in triplicate. The plates were incubated at 37°C in room temperature air for 12 hours.

[0140] A total of 25 mice in each treatment group were counted in triplicate plates for a total of 75 averages. Of the 25 animals in the control group, a total of 6 mice showed very low colonization (CFU / nasal cavity <1,500). The average CFU / nasal cavity of the remaining 19 animals in the control group was 11,051. TM Both the skin and nasal disinfectants and the molecular iodine-glycerol treatment significantly reduced MRSA in the nasal cavity. The average MRSA reduction with the 3M product was 2.15 logs, compared to a 2.40 log reduction with molecular iodine.

[0141] The use of binomial statistics can more accurately assess the clinical success of patients in this application, because the average reduction does not include an assessment of the proportion of individual patients who benefit. Therefore, in order to be considered a treatment success, a minimum standard of two log reductions was applied. Using this more appropriate standard, the 3M product showed 9 failures in 25 mice, while molecular iodine had only 3 failures. This demonstrates a statistically significant difference between the 3M product and the molecular iodine product described herein.

Claims

1. An emollient antimicrobial composition comprising an organic carrier molecule and molecular iodine, wherein the organic carrier molecule has a vapor pressure at standard atmospheric pressure that is at least 30% lower than the vapor pressure of molecular iodine and has a boiling point greater than 100°C at standard atmospheric pressure.

2. The emollient antimicrobial composition of claim 1, wherein the organic carrier molecule is propylene glycol, glycerin, or a combination thereof.

3. The emollient antimicrobial composition of claim 1 or 2, wherein the concentration of molecular iodine is from about 10 ppm to about 1000 ppm.

4. The emollient antimicrobial composition of claim 1 or 2 wherein the ratio of molecular iodine to all iodine species is at least about 70%.

5. The emollient antimicrobial composition of claim 1 or 2, wherein the ratio of molecular iodine to all iodine species is at least about 90%.

6. The emollient antimicrobial composition of claim 1 or claim 2, wherein the composition further comprises a gelling agent selected from the class consisting of synthetic hydrocolloids such as homopolymers of acrylic acid, such as those provided by Lubrizol Advanced Materials, Inc., Cleveland, OH, including Ultrez Ultrez Ultrez and Carbopols, including 934, 940, 980, SC-200; methyl glucoside derivatives; alcohol esters such as monoalcohol esters, polyol esters; polyethylene glycol (PEG) such as PEG-diisostearate, propoxylated PEG monolaurate, polyglycerol-3-laurate, natural hydrocolloids such as carrageenan, locust bean gum, guar gum, gum arabic, tragacanth gum, alginic acid or gelatin; and semi-synthetic hydrocolloids such as carboxymethylcellulose, methylcellulose and hydroxypropyl methylcellulose.

7. The emollient antimicrobial composition of claim 6, wherein the composition has a viscosity of 20 to 100,000 centipoise.

8. The emollient antimicrobial composition of claim 7 wherein the viscosity is from 150 to 25,000 centipoise.

9. The emollient antimicrobial composition of claim 7 wherein the viscosity is from 500 to 10,000 centipoise.

10. The emollient antimicrobial composition of claim 1, wherein said composition further comprises one or more organic molecules.

11. The emollient antimicrobial composition of claim 1 wherein the organic molecule is selected from the group consisting of monomethyl ether, acetate, amyl alcohol, ethyl acetate, butyl acetate, dimethyl sulfoxide, 1-propanol and 2-propanol, dimethyl sulfoxide, isopropanol and ethanol.

12. The emollient antimicrobial composition of claim 1, wherein said composition is packaged in a single compartment container.

13. The emollient antimicrobial composition of claim 1, wherein the composition is packaged in a two-compartment container that delivers the contents of the two compartments in a substantially simultaneous manner.

14. The emollient antimicrobial composition of claim 1, wherein the composition is packaged in a three-compartment container that allows for mixing of two or more of the contents of the compartments prior to delivery of the contents of all three compartments in a substantially simultaneous manner.

15. The emollient antimicrobial composition of claim 1, wherein the composition is packaged in a package comprising an integrated applicator such that the composition impregnates the applicator, wherein the applicator is designed to allow the emollient composition to be easily applied to mammalian tissue, such as the inner surface of a human nose.

16. The emollient antimicrobial composition of claim 1 further comprising a defined amount of an aqueous composition packaged in a compartment separate from the compartment containing molecular iodine.

17. The emollient antimicrobial composition of claim 15, wherein the aqueous composition comprises 5-95% of the mixed composition.

18. The emollient antimicrobial composition of claim 15 further comprising a pH control agent to control the pH of the thoroughly mixed composition within the range of 2.5 to 6.

0.

19. The emollient antimicrobial composition of claim 15 further comprising polymers, gelling agents and fragrances familiar to those skilled in the art which provide auxiliary characteristics to the composition.

20. The emollient antimicrobial composition of claim 19, wherein the gelling agent is selected from the class consisting of synthetic hydrocolloids such as homopolymers of acrylic acid, such as those provided by Lubrizol Advanced Materials, Inc., Cleveland, OH, including Ultrez Ultrez Ultrez and include 934, 940, 980, SC-200; methyl glucoside derivatives; alcohol esters, such as monoalcohol esters, polyol esters; polyethylene glycol (PEG) such as PEG-diisostearate, propoxylated PEG monolaurate, polyglycerol-3-laurate; natural hydrocolloids such as carrageenan, locust bean gum, guar gum, gum arabic, tragacanth gum, alginic acid or gelatin; and semi-synthetic hydrocolloids such as carboxymethylcellulose, methylcellulose and hydroxypropyl methylcellulose.

21. An emollient antimicrobial composition according to any one of the preceding claims further comprising a saturated fatty acid selected from the group consisting of lactic acid, myristic acid, 1-monolaurin, dodecanoic acid and caprylic acid.

22. An emollient antimicrobial composition according to any preceding claim formulated for skin application.

23. The emollient antimicrobial composition of claim 22 wherein the skin application is epidermal.

24. The emollient antimicrobial composition of claim 23, wherein the skin application is in the form of a cream, foam, gel, lotion or ointment.

25. The skin emollient antimicrobial composition of claim 23, wherein the skin application is in the form of a hand wash.

26. An emollient antimicrobial composition according to any preceding claim which is formulated for nasal use.

27. The skin-emollient antimicrobial composition of claim 26, wherein the nasal application is in the form of a spray.

28. An emollient antimicrobial composition as claimed in claim 27, wherein the spray dosage form is in the form of a metered dose inhaler.

29. The emollient antimicrobial composition of claim 26, wherein said composition kills airborne pathogens.

30. A method of treating a bacterial infection comprising administering a therapeutically effective amount of an emollient antimicrobial composition according to any one of the preceding claims.

31. A method of treating or preventing hospital acquired infections comprising administering an effective amount of an emollient antimicrobial composition according to any one of the preceding claims.

32. The method of claim 31, wherein the hospital-acquired infection is Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae, including E. coli, Klebsiella pneumoniae, Shigela, or Yersinia.

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