JP2016504383A - Body surface treatment composition and treatment method - Google Patents

Abstract

A method of treating a body surface with an active agent comprises administering a therapeutically effective amount of the composition to the body surface, the composition being effective in maintaining contact with the body surface for a duration of at least about 1 hour. A film is formed on the body surface. The composition meets the following requirements: about 0.0001% ≦ C ≦ about 0.4%, about 0.07% ≦ H ≦ about 70%, optionally antibacterial agent A, and a therapeutically effective amount of X; or 0% ≦ C ≦ About 0.4%, about 55% ≦ H ≦ about 70%, optionally antimicrobial agent A, and a therapeutically effective amount of X. All percentages are by weight of the total composition, C is a carbohydrate gum; H is a wetting agent; and X is an active agent, which has the effect of providing a therapeutic effect on the body.

Description

The present disclosure relates to a method for treating a human body surface with a skin antimicrobial composition and a topical active agent.
(Cross-reference of related applications)

  This application claims the benefit of priority of US Provisional Application No. 61 / 749,195 (“Barrier-Forming Composition with Active Agents and Method.”) Filed January 4, 2013. This application also claims the benefit of the priority of US Patent Application No. 14 / 063,974 (“Low-Tack Surface Anti-Microbial Coating Composition and Method of Application.”) Filed Oct. 25, 2013. Partial continuation application. This application also claims the benefit of the priority of US Patent Application No. 13 / 734,363 ("Long-Lasting Surface Anti-Microbial and Method of Application.") Filed January 4, 2013, some of which It is a continuation application. This application is also a priority benefit of US Provisional Application No. 61 / 829,608 (“Method for Reducing Microbial Load for Treatment of Disease Caused or Aggravated by Microorganisms or Relieving Symptoms Thereof”) filed May 31, 2013. Insist. The entire contents of the provisional application are incorporated herein by reference.

  Numerous topical compositions are available for treating human lesions such as skin lesions or mucosal surfaces. Such compositions include active agents for treating various conditions and diseases. However, topical compositions often have a limited effect because they are easily washed away or otherwise not kept in contact with the body surface for a period sufficient to maximize their effects. It has been. Many topical compositions are intermittent and temporary options that do not provide lasting protection.

US Patent Publication 2012/0270909

Yang, et al. "Concentrations and Size Distributions of Airborne Influenza A Viruses Measured Indoors at a Health Centre, a Day-Care Centre, and on Aeroplanes," J.R.Soc.Interface (Feb. 7, 2011) Frank-Albert Pitten and Axel Kramer, "Efficacy of Cetylpyridinium Chloride Used as Oropharyngeal Antiseptic," Arzneim.Forsch./Drug Res.51 (II), pp588-595 (2001) Department of Health and Human Services (Food and Drug Administration) (1994) Oral Health Care Drug Products for Over-the-Counter Human Use; Tentative Final Monograph for Oral Antiseptic Drug Products.Proposed Rules (21 CFR Part 356, Docket No. 81N -033A, RIN 0905-AA06). Federal Register 59: 6084-124 Chandra et al. "In vitro Growth and Analysis of Candida Biofilms" Nature Protocols 3 (12): 1909-1924 (2008) Pig Skin as Test Substitute for Evaluating Topical Antimicrobial Activity, "J. of Clinical Microbiology, p. 343-348 (Sept. 1986).

  A method of treating a body surface with an active agent includes administering a therapeutically effective amount of the composition to the body surface, the composition being effective in maintaining contact with the body surface for a duration of at least about 1 hour. A barrier coating is formed on the body surface. The composition meets the following requirements: about 0.0001% ≦ C ≦ about 0.4%, about 0.07% ≦ H ≦ about 70%, optionally antibacterial agent A, and a therapeutically effective amount of X; or 0% ≦ C ≦ About 0.4%, about 55% ≦ H ≦ about 70%, optionally antimicrobial agent A, and a therapeutically effective amount of X. All percentages are by weight of the total composition, C is a carbohydrate gum; H is a wetting agent; and A is an active agent, which has the effect of providing a therapeutic effect on the body.

  A method for killing microorganisms on a mammalian skin surface is to apply a composition comprising an antimicrobial agent to the skin surface; within the coating, the microorganisms contacted on the surface and the surrounding environment after performing the application step. Killing or neutralizing contacted microorganisms; forming a coating layer on the surface. The composition includes a wetting agent and an antimicrobial agent. The antibacterial agent includes a monoquaternary ammonium compound or a pharmaceutically acceptable salt thereof. The coating layer has a bactericidal or bacteriostatic effect of at least about 1 hour.

  The body surface treatment composition comprises about 0.0001% ≦ C ≦ about 0.4%, about 0.07% ≦ H ≦ about 70%, optionally antibacterial agent A, and a therapeutically effective amount of X; or 0% ≦ C ≦ about 0.4% About 55% ≦ H ≦ about 70%, optionally antibacterial agent A, and a therapeutically effective amount of X. All percentages are by weight of the total composition, C is carbohydrate gum, H is a wetting agent, A is an antimicrobial agent, and X is an active agent. The active agents include antacids, probiotics, vitamins, nutritional supplements, silver, antioxidants, cold or influenza symptomatics, anti-prion agents, immunostimulants, anti-diarrheal agents, antiemetics, local anesthetics , Topical analgesics, antipruritics (anti-itching agents), antiallergens, topical steroids, decongestants, antitussives, burns or sunburn agents, expectorants, antihistamines, topical NSAIDs, topical salicylates, hair growth agents, erectile dysfunction Therapeutic agents, topical antibiotics, topical wound treatment agents, antioxidants, hemorrhoid treatment agents, topical antifungal agents, anti-acne agents, scar treatment agents, psoriasis treatment agents, dry scalp treatment agents, anti-dandruff agents, lice killing agents , A hair care agent, a body odor improving agent, an antiperspirant, and a foot odor improving agent.

  As used herein, the indefinite article “a” and the definite article “the” mean “one or more” unless otherwise specified.

  In this specification, the terms "item" and "apparatus" are used interchangeably.

  The term “therapeutic” is also used herein for prophylactic treatment.

  As used herein, the term “or” does not have an exclusive meaning unless otherwise specified.

  As used herein, the term “individual” or “mammal” means a human or animal generally defined as a mammal.

  The term “lesion” is used herein with almost the same meaning as “disruption”.

  As used herein, the term “blocking” or “blocking” includes the meaning of blocking passage by capturing.

It is a flowchart which shows the result at the time of contacting with a processed and untreated inanimate surface, and microorganisms. FIG. 2 shows a proposed antimicrobial activity mechanism in one embodiment of a coating composition. FIG. 4 is a schematic diagram showing the formation of a barrier on the mucosal surface described in Experimental Example 2. It is the schematic which shows the evaluation method of the microorganisms growth in the upper chamber of a EHOM assay, and a lower chamber described in Experimental example 27-28. It is a figure which shows the photograph of the agar plate which shows microbial growth in the upper chamber of a EHOM assay, and a lower chamber described in Experimental example 27-28. It is a figure which shows the expanded cross-section photograph of the processed human oral mucosa (EHOM) by which the coating composition was processed and unprocessed in Experimental example 31-32. Photographs showing microbial growth and subsequent infection with C. albicans on untreated EHOM or EHOM treated with an exemplary coating composition as described in Experimental Examples 33-40 FIG. It is a figure which shows the photograph which shows the proliferation of microorganisms in the untreated EHOM described in Experimental Examples 33-40, or the EHOM treated with the formulation, and subsequent infection with S. mutans (Streptococcus mutans) . FIG. 4 shows photographs showing the growth of microorganisms derived from “flow-through” media (collected from the lower chamber) of EHOM treated with an exemplary coating composition described in Experimental Examples 33-40. LDH release by EHOM treated with saline (control group) or exemplary coating composition as described in Experimental Examples 40-47, followed by (A) C. albicans or (B) S. mutans infection It is a graph which shows. It is a graph which shows the antibacterial effect of the coating composition with respect to bacteria and fungi described in Experimental Examples 63-69. It is a figure which shows the scanning electron micrograph which shows S. sanguis, C. albicans, and S. mutans which were described in Experimental example 71-76, and was processed with the coating composition. FIG. 8 is a graph showing the activity of an exemplary coating composition against biofilms formed by bacteria and fungi as described in Experimental Examples 77-79. FIG. 8 is a graph showing the activity of an exemplary coating composition against a microbial biofilm after 1 minute exposure as described in Experimental Examples 80-81. It is a figure which shows the fluorescence micrograph which shows the effect of the example coating composition with respect to the cytopathic effect (CPE) of the MDCK cell infected with influenza (H1N1) described in Experimental example 85-86. FIG. 8 shows fluorescence micrographs showing the effect of exemplary coating compositions on H1N1 virus described in Experimental Examples 85-86. It is a graph which shows the level (determined by quantitative PCR) of the influenza virus in the infected cell processed and untreated with the film | membrane composition described in Experimental example 87-88. In the graph showing the direct antiviral activity (determined by quantitative PCR) of an exemplary coating composition prepared with or without preservatives and antibacterial agents against influenza virus (CPC) described in Experimental Examples 89-91 is there. FIG. 6 shows the activity during 6 hours of an exemplary coating composition against H1N1 virus, panel (A) is a graph showing the inhibition rate of virus growth compared to an untreated control group, panel (B) and (C) is a view showing a micrograph of an untreated cell (B), and (C) a micrograph of a cell treated with a coating composition. It is a graph which shows the activity of the formulation with respect to HIV described in Experimental example 94-96. FIG. 80 shows a Western blot showing the activity of Experimental Example 8 against Epstein-Barr Virus (EBV) described in Experimental Example 97. It is a figure which shows the photograph which proves the oral-mucosal-surface covering ability of an example coating composition. FIG. 6 shows photographs of time-lapse microscopy results of bacterial growth after 1 minute exposure to an exemplary coating composition described in Experimental Examples 162-163. The images show bacterial growth 20 minutes, 120 minutes, or 360 minutes after exposure, respectively. FIG. 7 is a graph showing the effect of a single dose of an exemplary coating composition on healthy human oral microbial load described in Experimental Examples 164-166, (A) microbial load in CFU compared to baseline, And (B) decrease in microbial load (%). FIG. 6 is a graph showing the effect over 5 days of an exemplary coating composition on oral bacterial levels in three healthy adults as described in Experimental Examples 167-169. FIG. 5 is a graph illustrating the effect of an exemplary coating composition on microbial load in the oral cavity after 5 days of use of the exemplary coating composition in 31 healthy subjects as described in Experimental Examples 170-198 . It is a graph which shows the microbial load in the oral-sample obtained from three typical research participants described in Experimental example 170-198. FIG. 2 is a schematic diagram illustrating an in vitro filter insertion base model for assessing microbial penetration across a barrier formed by an exemplary coating composition described in Experimental Examples 199-205. Shows the growth of MRSA biofilms on the surface of a silicone elastomer disc treated with PBS (control, A, C, E) and the coating composition of Experiment 7 (B, D, F) as described in Examples 219-224 It is a photograph. FIG. 6 is a photograph showing cell monolayers treated with different time intervals (a), (b), and (c) of the coating composition of Example 252 and the embodiment of Control Example 253 (d). FIG. 4 is a photograph of immunofluorescence showing a cell monolayer treated with different time intervals (a), (b), and (c) of the coating composition of Example 252 and the embodiment of Control Example 253 (d). 6 is a graph showing a test composition and a comparative product after water washing corresponding to Experimental Example 255. FIG. 6 shows a photograph depicting a gum-containing embodiment demonstrating differences in tackiness, viscosity, and thickness compared to a gum-free embodiment. FIG. 6 shows a photograph depicting a gum-containing embodiment demonstrating differences in viscosity, thickness, and surface coverage as compared to a gum-free embodiment. It is a figure which shows the photograph of the agar plate which imprinted the pig skin sample processed by infection corresponding to the experiment example 261. It is a figure which shows the photograph of the agar plate which imprinted the pig skin sample corresponding to the experiment example 262 which was infected and processed.

  In one embodiment, a stable solution composition comprising various active agents is disclosed for topical treatment of a mammalian body surface. In one embodiment, the therapeutically effective amount of the composition is non-toxic and safe for mammals (ie, does not damage mucosa or other body surfaces).

  In one embodiment, the topical antimicrobial composition serves to prevent microbial growth for extended periods of time by bacteriostatic or bactericidal action. In one embodiment, the composition, such as a disinfectant, is long lasting and powerful and kills a wide range of microorganisms (eg, fungi, bacteria, and viruses). The composition acts to capture and neutralize and / or kill microorganisms that are pre-existing on the treated surface and / or microorganisms that have subsequently contacted the exposed (top) surface to which the antimicrobial coating has been applied. In one embodiment, the composition captures and kills or neutralizes pre-existing microorganisms on the treated surface, and / or after the barrier-forming composition application is performed, It is a barrier-forming film that has an effect of trapping and killing or neutralizing microorganisms adhering to the exposed surface.

  In one embodiment, the composition is a barrier-forming composition that is stable and increases the duration and effectiveness of the active agent on the body surface. In one embodiment, the therapeutically effective amount of the barrier-forming composition is non-toxic and safe for mammals (ie, does not damage mucous membranes or other body surfaces). The barrier-forming composition forms a barrier coating that keeps the active agent on the body surface. Various active agents may be included in the composition embodiments.

  In one embodiment, the composition is a topical antimicrobial composition for the treatment of mammalian skin. In one embodiment, a topical antimicrobial agent for the treatment of mammalian skin is a low tack variation of the composition. Other embodiments of the topical skin antibacterial agent may also include gums and / or higher concentrations of wetting agents, as described below.

In low tack embodiments, the coating composition satisfies the following requirements:
About 0.07% ≦ H ≦ about 10%; and
0.0005% <A,
Where H is a wetting agent and A is an antibacterial agent;
All percentages are by weight of the total composition.

  In one embodiment, the concentration of wetting agent may be from about 3% to about 8%, from about 0.35% to less than about 1%, or from about 0.1% to less than about 0.5%. In another embodiment, the wetting agent of the coating composition satisfies the following requirements: about 0.07% ≦ H <1%. This low wetting agent embodiment reduces the viscosity or adhesion of the composition and provides a better feel to the inanimate surface. Antimicrobial agents may be present in the range of about 0.0005% to 5% weight. Additional types of antimicrobial agents are also described below.

  In low tack embodiments, the coating composition is essentially free of carbohydrate gum, eg, contains less than 0.00009% carbohydrate gum, no detectable carbohydrate gum, or no carbohydrate gum. The term “essentially free” includes not including at all.

  The composition comprises about 50 to about 98% water by weight, such as about 75 to about 97% water, or about 85 to about 95% water.

  In one embodiment, the composition consists essentially of a wetting agent and an antibacterial agent, in addition to a preservative, flavoring agent, or other agent that does not affect the scavenging or antibacterial effect of the composition. Including only. As used herein, “consists essentially of” or “consisting essentially of” has the meaning typically applied to the specific material as well as the basis of the composition. Meaning that does not materially affect the target and the new property (s). In embodiments, this may include less than 1%, less than 0.01%, or less than 0.0001% non-specific material by weight. In one embodiment, the low tack composition may include additional active agents as described herein.

  In such embodiments, when used as a skin topical antibacterial agent, the antibacterial agent may be a monoquaternary ammonium compound or a pharmaceutically acceptable salt thereof, for example, QAC, cetrimide, benzal chloride. It may be luconium, cetalkonium chloride, cetylpyridinium chloride, myristalkonium chloride, polycide, and the like. In one embodiment, the antimicrobial component of the composition may consist essentially of a monoquaternary ammonium compound or a pharmaceutically acceptable salt thereof, and cetylpyridinium chloride contains a small amount of a wetting agent as well as the above. Excellent efficacy was exhibited with only preservatives, flavoring agents and / or other agents that did not affect the scavenging action and antibacterial activity of the composition. Such a composition has several safety and environmental advantages over other skin antiseptic topical compositions. See Experimental Example 256. In one embodiment, the antimicrobial component consists essentially of cetylpyridinium chloride, as it is the only agent that acts as an antimicrobial agent.

In one embodiment, the composition comprises a carbohydrate gum (C), a wetting agent (H), optionally an antibacterial agent (A), and an active agent (X), and the barrier-forming composition meets the following requirements:
About 0.0001% ≦ C ≦ about 0.4%;
About 0.07% ≦ H ≦ about 70%;
Optionally 0.0005% <A; and a therapeutically effective amount of X;
Or
0% ≦ C ≦ about 0.4%;
About 55% ≦ H ≦ about 70%;
Optionally 0.0005% <A; and a therapeutically effective amount of X.
All percentages are by weight of the total composition. After being applied effectively, the barrier layer containing any antibacterial agent exhibits a bactericidal or bacteriostatic effect. The therapeutically effective amount of X depends on the active agent used, but usually exceeds the effective amount of the active agent at typical dosages as taught in the prior art except in combination with the barrier-forming composition. Absent. For example, the active agent may be present in an amount of at least about 0.0005%, such as from about 0.001% to about 0.01%, about 0.1% to about 1%, or about 2% to about 50%. Good. In one embodiment, the amount of X is less than the known drug dose of the prior art, such as 10% to 95% less than the known prior art minimum effective dose, or 25% to 75 less than the known prior art minimum effective dose. % Less or 50% less than the known prior art minimum effective dose.

In another embodiment, the barrier-forming composition satisfies the following requirements:
About 0.01% ≦ C ≦ about 0.4%;
About 4.5% ≦ H ≦ about 65%;
Optionally 0.0005% <A; and a therapeutically effective amount of X;
Or
0% ≦ C ≦ about 0.4%;
About 55% ≦ H ≦ about 65%;
Optionally 0.0005% <A; and including a therapeutically effective amount of X,
Where C is a carbohydrate gum; H is a wetting agent; A is an antibacterial agent; and X is an active agent, which has the effect of providing a therapeutic effect on the body.

In one embodiment of a barrier-forming composition comprising one or more active agents, the composition meets the following requirements:
About 0.0001% ≦ C ≦ about 0.4%,
About 0.07% ≦ H ≦ about 70%; and a therapeutically effective amount of X;
Or
0% ≦ C ≦ about 0.4%,
About 55% ≦ H ≦ about 70%; and including a therapeutically effective amount of X;
Where all percentages are by weight of the total composition;
C is a carbohydrate gum; H is a wetting agent; and X is an active agent, which has the effect of providing a therapeutic effect on the body.

  In another embodiment, the wetting agent of the composition satisfies the following requirements: about 0.07% ≦ H <1%. This low wetting agent embodiment reduces the viscosity of the composition.

  In one embodiment, the barrier-forming composition includes glycerin or one or more similar moisturizing substances. In one embodiment, the concentration of humectant ranges from about 0.07% to about 10% by weight of the total composition, such as about 3% to about 8%, about 0.35% to less than about 1%, or about 0.1%. % To less than about 0.5%. In another embodiment, the wetting agent ranges from about 2% to about 70% by weight of the total composition, such as from about 4.5% to about 65%, from about 7% to about 35%, or from about 15% to about It may be 45%. Wetting agents similar to glycerin can generally be classified as polyols. Examples of the wetting agent include glycerin, sorbitol, xylitol, propylene glycol, polyethylene glycol, and mixtures thereof. In one embodiment, glycerin can be used at high concentrations, such as about 55% to about 65%, in the absence of gum.

  In one embodiment, the composition comprises a gum. The gum may be, for example, a polysaccharide, xanthan gum, gum arabic, or guar gum. In general, such gums can be classified as carbohydrate gums with a negative charge as a whole. In another embodiment, the gum may be xanthan gum, guar gum, gum arabic, tragacanth gum, karaya gum, locust bean gum, locust bean gum, and pectin, for example. These gums can generally be classified as carbohydrate gums with a negative charge as a whole. In one embodiment, the gum may be present from about 0.0001% to about 0.4%, such as from about 0.0005% to about 0.25% by weight in the total composition. In another embodiment, the gum may be present from about 0.01% to about 0.4%, such as from about 0.25% to about 0.35%, from about 0.05% to about 0.25%, or about 0.4% by weight in the total composition. Good.

  In one embodiment, the composition includes a wetting agent, an active agent, and optionally a gum, and when the gum is present, the gum is present in an amount from about 0.0001% to about 0.4% by weight of the total composition.

  In one embodiment, an antimicrobial agent is present in the composition. For example, the composition may include one or more antiviral agents, or antifungal agents, or antibacterial agents, or combinations thereof. Moreover, the effect of such an antibacterial agent includes bacteriostatic action and / or bactericidal action.

  Antibacterial agents include, for example, monoquaternary ammonium compounds (QAC, cetrimide, benzalkonium chloride, cetalkonium chloride, cetylpyridinium chloride, myristaronium chloride, polycide), biquaternaries and bisbiguanides (chlorhexidine, barquat, hibiten) ), Biguanides, polymer biguanides, polyhexamethylene biguanides, vantosyl, cosmosyl, diamidine, halogen-containing compounds including chlorine and iodine compounds, silver and silver antibacterial compounds, peracetic acid (PAA), silver sulfadiazine, phenols, bisphenol Cationic antibacterial agents such as halophenols, including but not limited to, hydrogen peroxide, hexachlorophene, but not limited to chloroxylenol (4-chloro-3,5-dimethylphenol; p-chloro-m-xylenol) and the like Pharmaceutically acceptable salts thereof, but are not limited thereto.

  Antimicrobial agents have both bactericidal and bacteriostatic properties, and different classes of antibacterial agents such as tetracycline, chloramphenicol, fusidic acid, fluoroquinolone, macrolide antibacterial agents, oxazolidinones, quinolone carboxylic acids, Naphthyridone carboxylic acid, citral, trimethoprim and sulfamethoxazole (alone and in combination), aminoglycoside, polymyxin, penicillin and derivatives thereof may be, or may contain. Antibacterial agents can also include, for example, the following classes of antifungal agents: azoles, polyenes, echinocandins, and pyrimidines. Any combination of the above antibacterial agents is also contemplated. Many of the aforementioned antimicrobial agents are cationic species or pharmaceutically acceptable salts thereof, and in one embodiment, a cationic antimicrobial agent is utilized in the composition. In one embodiment, the composition is an agent limited to releasing vapor such as chlorine dioxide or chlorine dioxide to produce a reactant.

  In one embodiment, the composition does not cause microbial mutation or resistance development. This is because the mechanism of action on microorganisms is due to the barrier and the selected antimicrobial agent.

  The optional antimicrobial agent is, for example, an amount ranging from about 0.0005% to 5% by weight in the total composition, such as from about 0.0025% to about 1%, from about 0.005% to about 0.006%, or from about 0.0006% to about 0.003%. May be present. In another embodiment, the antimicrobial agent is present, for example, in an amount ranging from about 0.05% to about 0.1%, such as from about 0.05% to about 0.06%, or from about 0.06% to about 0.1%, by weight in the total composition. Also good. In one embodiment, the amount of antimicrobial agent is, for example, about 5% or less, about 3% or less, or about 1.5% or less, provided that the antimicrobial agent used does not cause solubility problems at higher concentrations. .

  In embodiments, the composition further includes copovidone and other lubricants, parabens such as methylparaben and propylparaben, flavoring agents, preservatives such as sodium benzoate, monosodium phosphate and disodium phosphate. Other ingredients such as buffering agents, sweeteners, ethylene oxide hydrogenated castor oil, and carboxymethylcellulose may also be included. These components may be included, for example, in amounts ranging from about 0.01% to about 5%, such as from about 0.1% to about 2%, by weight percent in the total composition. In another embodiment, the component may be included in an amount ranging, for example, from about 0.0001% to about 0.05%. Buffering agents (such as monosodium phosphate and disodium phosphate) can also be used.

  Purified water and / or alcohol can be used as a diluent component of the composition. In one embodiment, the composition is a free flowing liquid suitable for spraying. This is in contrast to pastes or toothpastes that are usually not free-flowing and not suitable for spraying. In addition, in one embodiment, the composition does not include abrasives commonly used for toothpaste.

  In one embodiment, substantially free-flowing and substantially free of agglomerates is determined by passing the composition through a 140 US mesh (0.10 mm pore size), and 95 to 100 of the composition. % (Weight), for example 96% to 99.9%, passes after 30 seconds. In this embodiment, the composition is not a gel.

  In one embodiment, the composition consists essentially of a gum, a wetting agent, and an active agent, and includes only preservatives or flavoring agents that do not affect the barrier or active agent action of the composition. In one embodiment, the composition does not include agents that act on the teeth and / or gums, such as abrasives (such as those used in toothpaste), tooth whitening agents, or desensitizers. In one embodiment, the composition does not include cellooligosaccharides. In one embodiment, the antimicrobial agent does not include lipids such as fatty acid ethers or fatty acid esters of polyhydric alcohols or alkoxylated derivatives thereof. In one embodiment, the composition does not include one or more of sustained release agents, allergy alleviating compounds, azelastine, silicone base oil, essential oil, polyvinyl pyrrolidone, polyvinyl alcohol and potassium nitrate. In one embodiment, the composition does not include volatile organic compounds such as volatile alcohols. In one embodiment, the composition does not include all alcohols. In one embodiment, the composition does not include a surfactant or foaming agent. To avoid misunderstanding, any description above should not be construed as implying that all embodiments do not contain these compounds.

  In one embodiment, the method of making the composition includes mixing and heating ingredients including carbohydrate gum, a wetting agent, and an optional antimicrobial agent. In one embodiment, the heating step is replaced with a step of extending the mixing time. Other ingredients including the active agent are also mixed in a single or multiple mixing steps. All the components of the barrier-forming composition are mixed at once to produce a composition with a stable shelf life. This is in contrast to compositions having active ingredients that must be added separately in a short time to use. Thus, in one embodiment, the composition is a stable, single component composition that, when used, does not need to be mixed with other compositions to activate.

  In one embodiment, the composition is a liquid and is not cellular. In one embodiment, the composition is a solution, not an emulsion or microemulsion.

  As described above, in one embodiment, the composition is suitable for spraying and thus its viscosity is also suitable for spraying. In one embodiment, the composition has a viscosity of less than 500 cps, such as a viscosity of about 490 cps to about 10 cps, or about 400 cps to about 15 cps. In another embodiment, the composition has a viscosity of about 16 cps to about 20 cps, such as a viscosity of about 17 cps to about 19 cps.

  Post antimicrobial effect (PAE) is defined as inhibiting the growth of microorganisms that persist after limited exposure to antimicrobial agents. Longer PAEs may be beneficial for antimicrobials because they can sustain microbial growth continuously, and agents with longer PAEs need to be administered less frequently than agents with shorter PAEs. May affect the plan. In embodiments comprising an antimicrobial agent, the composition may have a PAE that lasts about 6 hours or more, such as from about 6 hours to about 16 hours, or from about 16 hours to 24 hours.

  In one embodiment, the composition is non-toxic to humans, wherein at least a portion of the composition may be ingested and is safe for human consumption. For example, at least a therapeutically effective amount of the composition is safe for human consumption.

  Without being bound by theory, since the composition is not hydrophilic, the composition can have a greater affinity to adhere to and cover the mucosal surface. Furthermore, in one embodiment, the antimicrobial agent embedded in the non-hydrophilic composition allows for sustained antimicrobial activity on the treated surface. In one embodiment, the composition is itself amphiphilic or has an amphiphilic component.

  One measure of hydrophilicity is the Rf (relative front) value determined by underwater chromatography. In one embodiment, the Rf value in water of the composition is from 0 to about 0.25, such as from about 0.0001 to about 0.15, or from about 0.03 to about 0.1.

  In one embodiment, the pH of the composition is from about 4 to about 8, from about 5 to about 7, or from about 6 to about 7.5. In another embodiment, the composition has a pH of about 5.5 to about 8, and an antimicrobial agent such as cetylpyridinium chloride is most effective.

  In one embodiment, the coating composition is non-flammable.

  In general, a dual action mechanism that provides a barrier to microorganisms and an antimicrobial agent provides a long-lasting effect characterized by both in vitro and simulated in vivo. An in vivo example is shown below. In vivo examples have shown that the barrier-forming composition has a bactericidal effect (bactericidal or bacteriostatic) for at least 6 hours. The barrier properties themselves are examined in a simulated in vivo test (targeting artificial human mucosal EHOM) and the duration of the barrier itself is greater than about 6 hours, for example greater than about 8 hours, about 6 hours to about 16 hours, about 24 hours It has been shown to be significantly extended to time or longer. Also, in in vitro tests, the antibacterial effect is more than about 2 hours, more than about 6 hours, and more than 8 hours, about 6 hours to about 16 hours, and about 24 hours or longer depending on the microorganisms examined. It was shown to be extended significantly.

  In one embodiment, the active agents that can be used in the barrier-forming composition are those that have delayed release or sustained release, or have an efficacy that improves the longer they exist on the body surface. Exemplary active agents include antacids, probiotics, vitamins, nutritional supplements, silver, antioxidants, cold or flu symptomatics, anti-prion agents, immunostimulants, or combinations of the above . Further examples of active agents include antidiarrheal agents, antiemetics, local anesthetics, local analgesics, antitussives, antiallergens, topical steroids, decongestants, antitussives, burns or sunburn agents , Expectorant, antihistamine, topical NSAID, topical salicylate, hair growth agent, erectile dysfunction, topical antibiotic, topical wound treatment, antioxidant, hemorrhoid treatment, topical antifungal, anti-acne, scar Includes therapeutic agents, psoriasis therapeutic agents, dry scalp therapeutic agents, anti-dandruff agents, lice killing agents, hair care agents, body odor improving agents, antiperspirants, foot odor improving agents.

  Unless otherwise stated in the following more specific drug review, the effective amount of active agent is comparable to or less than the amount used in conventional drugs. Due to the barrier retention properties of the composition, it is anticipated that a smaller amount of active agent will be required for similar effects than those conventionally used.

  In general, an active agent can be included in the composition as long as it is soluble in an effective amount or at least miscible with the composition in an effective amount and does not destroy the barrier-forming properties of the composition. .

  In a general embodiment of a barrier-forming composition that includes one or more active agents, the agents are effective for topical treatment of mammalian skin. In another embodiment of the barrier-forming composition comprising one or more active agents, the agents are effective in treating the mammalian body and / or mucosa.

  In embodiments having a local anesthetic active agent, the barrier-forming composition is used to numb the pain. The composition may be applied, for example, to the mucous membrane of the oral cavity or pharynx, for example to treat sore throat pain. In another embodiment, the composition may be applied to the skin, for example to treat pain in the skin or underlying muscle. The composition may be sprayed, smeared, rubbed, spin coated, or dispersed on the skin, or swallowed or exhaled in the oral cavity. Exemplary local anesthetics include benzocaine, butamben, dibucaine, oxybuprocaine, pramoxine, proparacaine, proxymetacaine, and tetracaine, phenolic compounds, trolamine salicylic acid or methyl lidocaine and tetracaine.

In embodiments having an analgesic active, the barrier-forming composition is used to reduce pain. The composition may be applied, for example, to the oral or pharyngeal mucosa, for example to treat sore throat pain or for absorption into the circulating blood. In another embodiment, the composition may be applied to the skin, for example to treat pain in the skin or underlying muscle. The composition may be sprayed, smeared, rubbed, spin coated, or dispersed on the skin or mucous membranes, or swallowed or spited into the oral cavity. Exemplary analgesics include propionic acid derivatives, naproxen, ibuprofen, acetic acid derivatives, indomethacin, etodolac, enolic acid derivatives, fenamic acid derivatives, _COX- 2 derivatives, acetaminophen, sulfonanilide, diclofenac, capsaicin, NSAID, Ibuprofen, trolamine salicylic acid or methyl salicylate, mensacin and zostrikes are included.

  In embodiments having an antipruritic active, the barrier-forming composition is used to reduce itching of the skin or mucous membranes. The composition may be applied, for example, to the oral cavity, pharynx, vagina, or anal mucosa. In another embodiment, the composition may be applied to the skin, for example to treat itching. The composition may be sprayed, smeared, rubbed, spin-coated, or dispersed on the skin or mucous membrane. Exemplary anti-pruritic active agents include antihistamines such as diphenhydramine, corticosteroids such as hydrocortisone, local anesthetics such as benzocaine, counter stimulants such as mint oil, menthol, camphor.

  In embodiments having anti-allergen active agents, the barrier-forming composition is used to reduce itching of the skin or mucous membranes. The composition may be applied to, for example, the oral cavity, pharynx, vagina, or anal mucosa to transport the active agent and absorb it into the systemic circulation. In another embodiment, the composition may be applied to the skin to treat itching or rash on the skin, for example due to an allergic reaction. The composition may be sprayed, smeared, rubbed, spin-coated, or dispersed on the skin or mucous membrane. Exemplary anti-allergen active agents include antihistamines such as diphenhydramine, cetirizine, fexofenadine, and eucalyptol.

  In embodiments having a steroid active agent, the barrier-forming composition is used to reduce inflammation of the skin or mucosa. The composition may be applied to, for example, the oral cavity, pharynx, vagina, or anal mucosa to transport the active agent and absorb it into the systemic circulation. In another embodiment, the composition is for treating conditions such as skin irritation, itching or rash, or atopic dermatitis, psoriasis, eczema, seborrhea, insect bites, and contact dermatitis. It may be applied to the skin. The composition may be sprayed, smeared, rubbed, spin-coated, or dispersed on the skin or mucous membrane. Exemplary steroid active agents include cortisone, fluocinolone, desonide, prednicarbate, and fluticasone propionate.

  In embodiments having a burn or sunburn mitigant, the barrier-forming composition is used to reduce burn discomfort or promote healing. The composition may be applied to the affected area, for example. The composition may be sprayed, spin-coated, smeared, rubbed or dispersed on the skin. Exemplary active agents include aloe vera, steroids, and NSAIDs. Active agents such as β-carotene and / or lycopene may be effective as sunscreen protectors and preventatives.

  In embodiments having a counterstimulant, the barrier-forming composition is used to reduce skin or mucosal irritation. The composition may be applied, for example, to the nasal cavity, oral cavity, or pharyngeal mucosa or skin. The composition may be sprayed, spin-coated, rubbed, smeared, or dispersed on the mucous membrane. Exemplary counter-irritants include nifedipine, α-bisabolol, canola oil, glycerin, hexapeptide, and those that treat pain and rash by causing a warm and cold sensation, such as camphor, eucalyptus, menthol, or Ichaxou. included.

  In embodiments having a hair growth agent, the barrier-forming composition is for hair growth, such as in the treatment of androgenetic alopecia, alopecia areata, or more severe forms of alopecia (global or systemic). Used for. The composition may be applied to, for example, the scalp or other skin areas with normal hair such as the face. The composition may be sprayed, spin-coated, rubbed, smeared, or dispersed on the scalp. Exemplary hair growth agents include stimulants such as minoxidil, pepper, ketoconazole, and finasteride.

  In embodiments having an erectile dysfunction therapeutic, the barrier-forming composition is used to treat male impotence or erectile dysfunction. The composition may be applied to the nasal cavity, oral cavity, or pharyngeal mucosa or skin for absorption into the circulating blood, for example. The composition may be sprayed, spin-coated, rubbed, smeared, or dispersed in a male genitalia. The composition may be sprayed, spin-coated, rubbed, smeared, or dispersed on the scalp. Exemplary therapeutic agents for erectile dysfunction include sildenafil, tadalafil, vardenafil, alprostadil and yohimbine.

  In embodiments having a wound treatment agent, the barrier-forming composition is used to reduce wound discomfort or promote healing. The composition may be applied to the affected area, for example. The composition may be sprayed, spin-coated, smeared, rubbed or dispersed on the skin. Exemplary active agents include NSAIDs, antibacterial agents, and tissue regeneration agents. In one embodiment, the wound dressing may be treated with the barrier-forming composition immediately prior to application, or may be packaged as a pretreated wound dressing.

In embodiments having an antacid active agent, the barrier-forming composition is used for the treatment of acid reflux or gastric hyperacidity. The composition may be applied, for example, to the mucous membranes of the throat and pharynx, or oral mucosa, and can be coated on the stomach when the barrier-forming composition is swallowed or exhaled. The composition may be sprayed into the oral cavity or swallowed or exhaled in the oral cavity. Exemplary antacid activators include calcium and magnesium carbonates, magnesium hydroxide and aluminum, sodium carbonate, sodium bicarbonate, and C ₇ H ₅ BiO ₄ and mixtures thereof.

  In embodiments having a probiotic active agent, the barrier-forming composition is used for the treatment of various conditions such as enteritis, diarrhea, genitourinary infections, intestinal infections or inflammation, or allergies. The composition may be applied, for example, to the mucous membrane of the mouth, nose, anus, vagina, or pharynx, and the stomach can be coated by swallowing the barrier-forming composition. The composition may be sprayed into the oral cavity or swallowed or exhaled in the oral cavity. Exemplary probiotics include lactic acid bacteria (LAB) and bifidobacteria. Probiotic yeast or Neisseria gonorrhoeae are other examples. Probiotic active agents may be less compatible in embodiments of the composition containing antimicrobial agents, but they are used in separate embodiments to recover beneficial microorganisms after administration of the antimicrobial agent May be.

  In embodiments having a nutraceutical, the barrier-forming composition is used for the treatment or prevention of various conditions such as hypercholesterolemia, cancer, deterioration of arterial health, cardiovascular disease and the like. The composition may be applied, for example, to the mucous membrane of the mouth, nose, anus, vagina, or pharynx, and the stomach can be coated by swallowing the barrier-forming composition. The composition may be sprayed into the oral cavity or swallowed or exhaled in the oral cavity. Exemplary nutritional supplements include resveratrol from red grape products, flavonoids of citrus, tea, wine, and dark chocolate, anthocyanins found in berries, soluble dietary fiber products such as psyllium seed husk, broccoli (sulforaphane) Plant, and herbal extracts such as alpha-linolenic acid from spring, spring, clover (isoflavonoid), flax or chia seed, omega-3 fatty acid in fish oil, ginseng and garlic oil.

  In embodiments having an antioxidant, the barrier-forming composition is used for the treatment or prevention of various conditions such as heart disease or neurological disease. The composition may be applied, for example, to the mucous membrane of the mouth, nose or pharynx, and the stomach can be coated by swallowing the barrier-forming composition. The composition may be sprayed into the oral cavity or swallowed or exhaled in the oral cavity. Exemplary antioxidants include thiols, carotene, ubiquinol, ascorbic acid, or polyphenols, which can be either hydrophobic or hydrophilic.

  In one embodiment, the common cold and influenza drugs are active agents in the barrier-forming composition, and the composition is used for the treatment or prevention of cold and influenza symptoms. The composition may be applied, for example, to the mucous membrane of the mouth, nose or pharynx, and the stomach can be coated by swallowing the barrier-forming composition. Exemplary agents include decongestants, antidiarrheal agents, antiemetics, and antihistamines, and further details are individually described herein.

  In embodiments with antihistamines, the barrier-forming composition is used for the relaxation of upper airway respiratory mucus. The composition may be applied, for example, to the nose, mouth, or pharyngeal mucosa, or in another embodiment to the eyes or ears. The composition can be sprayed, spin-coated, dropped or dispersed on the mucosa. Exemplary antihistamines include azelastine, hydroxyzine, desloratadine, cyproheptadine, emedastine, levocabastine, carbinoxamine, levocetirizine, fexofenadine, diphenhydramine, brompheniramine, loratadine, clemastine, chlorpheniramine and cetirizine.

  In one embodiment, the anti-prion agent is an active agent in the barrier-forming composition, and the composition is for the treatment or prevention of brain conditions such as Alzheimer's disease or other prion diseases such as Kruo disease or mad cow disease. Used for. The composition may be applied, for example, to the mucous membrane of the mouth, nose or pharynx, and the stomach can be coated by swallowing the barrier-forming composition. Exemplary anti-prion agents are quinoline or acridine rings attached via tethers within a planar aromatic structure. This structure includes other compounds such as sulfated glycans or trimesic acid.

  In embodiments having an immunostimulatory active agent, the barrier-forming composition is used to stimulate the body's immune system. The composition may be applied, for example, to the mucous membrane of the mouth, nose or pharynx, and the stomach can be coated by swallowing the barrier-forming composition. The composition may be sprayed into the oral cavity or swallowed or exhaled in the oral cavity. Exemplary immunostimulants include specific and non-specific immunostimulants, endogenous immunostimulants, deoxycholic acid, macrophage stimulants, synthetic immunostimulants, macrokine, imiquimod, resiquimod, and granulocyte macrophage colonies Contains stimulatory factors. The immunostimulant becomes particularly effective in combination with the antibacterial agent of the composition, and may prevent disease.

  In embodiments having a vitamin active agent, the barrier-forming composition is used to treat vitamin deficiency or to supply the body with the vitamins needed. The composition may be applied, for example, to the mucous membrane of the mouth, nose or pharynx, and the stomach can be coated by swallowing the barrier-forming composition. The composition may be sprayed into the oral cavity or swallowed or exhaled in the oral cavity. Exemplary vitamins include vitamins A, B, C, D, E, and K, and certain types of subscripts.

  In embodiments having an anti-diarrheal active agent, the barrier-forming composition is used for the treatment of diarrhea. The composition may be applied, for example, to the mucous membrane of the mouth, nose, anus, vagina, or pharynx, and the stomach can be coated by swallowing the barrier-forming composition. The composition may be sprayed into the oral cavity or swallowed or exhaled in the oral cavity. The composition can be applied to the anal mucosa with an enema applicator. Exemplary anti-diarrheal active agents include, for example, anti-inflammatory solutions such as bismuth disalicylate, bulking agents such as methylcellulose, guar gum or vegetable fibers (absorbers such as bran, sterklia, isagol, methylcellulose, opioids, And loperamide hydrochloride.

  In embodiments having an antiemetic active, the barrier-forming composition is used for the treatment of nausea. The composition may be applied to the mucous membrane of the oral cavity or pharynx, for example, and can be coated on the stomach by swallowing the barrier-forming composition. The composition may be sprayed into the oral cavity or swallowed or exhaled in the oral cavity. Exemplary antiemetic actives include, for example, olanzapine, 5-HT3 receptor antagonist, dopamine antagonist, dolasetron, NK1 receptor antagonist, aprepitant, histamine H1 receptor antagonist, cyclidine, diphenhydramine, cannabinoid, cannabis, dronabinol, benzodiazepine , Midazolam, lorazepam, anticholinergic drugs, hyoscine, steroids, and dexamethasone.

  In embodiments having a decongestant active agent, the barrier-forming composition is used to reduce excess mucus. The composition may be applied, for example, to the nose, mouth, or pharyngeal mucosa. The composition can be sprayed, spin-coated, or dispersed on the mucosa. Exemplary decongestants include pseudoephedrine, phenylephrine, ephedrine, levomethamphetamine, naphazoline, oxymetazoline, phenylpropanolamine, propylhexedrine, synephrine, and tetrahydrozoline.

  In embodiments having an antitussive, the barrier-forming composition is used for cough reduction. The composition may be applied, for example, to the nose, mouth, or pharyngeal mucosa. The composition can be sprayed, spin-coated, or dispersed on the mucosa. Exemplary antitussives include antitussives, dextromethorphan, codeine, noscapine, bromhexine, acetylcysteine, expectorants, mucolytics, and honey.

  In embodiments with expectorants, the barrier-forming composition is used for the relaxation of upper airway respiratory mucus. The composition may be applied, for example, to the nose, mouth, or pharyngeal mucosa. The composition can be sprayed, spin-coated, or dispersed on the mucosa. Exemplary expectorants include acetylcysteine and ambroxol, guinefecin.

  In one embodiment, the barrier-forming composition having the active agent also includes an antimicrobial component that prevents microbial growth over a long period of time by bacteriostatic or bactericidal action. The combined barrier coating and antimicrobial agent act synergistically to neutralize and / or block microorganisms that have recently adhered to the treated surface and / or microorganisms that have subsequently contacted the exposed (top) surface of the barrier coating. Or kill, thereby providing a long-lasting antimicrobial agent that is significantly more powerful than the antimicrobial agent alone. The barrier coating captures and kills or neutralizes existing microorganisms on the treated surface and / or adheres to the top of the barrier, ie, the exposed surface of the barrier coating, after application of the barrier-forming composition is performed. It has the effect of capturing and killing or neutralizing microorganisms.

  Without being bound by theory, the mechanism of action of a barrier-forming composition containing an antimicrobial agent is a synergistic dual action that first traps bacteria within the formed barrier coating and then kills it with an antimicrobial active ingredient. It is based on the mechanism. In one embodiment, the barrier-forming composition is not hydrophilic and is not bound by theory, but has been theorized to enhance sustained efficacy.

  A similar dual action mechanism that acts as a seal on the skin or mucosal surface can also be provided by a barrier coating with an active substance. Active agents have activity recognized in the art and are included in the barrier composition to maintain contact with the surface for extended periods of time, thereby increasing the duration on the body surface. Brought about.

  As shown in the examples below, using at least the following 10 approaches, a composition comprising no active agent, a composition comprising only an antibacterial agent, and a composition comprising an antibacterial agent and a homeopathic active agent The characteristics were evaluated. (1) in vitro antimicrobial susceptibility test, (2) in vitro time kill assay, (3) in vitro biofilm model, (4) in vitro filter insert base model, (5) in vivo-like manipulated human oral mucosa (EHOM ) Model, (6) electron microscopic evaluation, (7) hydrophobicity assay, (8) physicochemical compatibility assay, (9) cell culture-based model using monolayer human cell line, and (10) human clinical test.

  Barrier-forming compositions are particularly useful for individuals who are at high risk for causing the disease for which the active ingredient is intended to be treated. Due to the extended duration and barrier coating enhancing activity, such persons may benefit from administration of the barrier-forming composition in repeated doses for continuous and aggressive treatment. For example, the extended duration and effectiveness of the composition is in an increased state of chronic pain or regular pain (painful medical practice) individuals or more frequently requiring active agents. It can be particularly useful for individuals, such as individuals with vitamin deficiencies (vitamin active agents).

  A high risk state is a high risk of serious complications resulting from not treating the disease efficiently, or a high risk of exposure to environmental conditions or contamination that causes a high risk, such as a high risk of allergic reactions due to allergen contamination , May be due to.

  In one embodiment, administration of the barrier-forming composition comprising an active agent is performed in response to recognition of the need for treatment with the active agent, as is typical for the active agent. However, in another embodiment, administration is recognized or expected to require treatment with the active agent in the future, eg, later than currently recognized in the treatment plan timeframe. May be performed in response to the need for such active agents recognized in the future. The extended duration of the composition facilitates such use. For example, extended duration utilizes barrier-forming compositions well before the need for antacids, antiallergens, antiemetics, or local muscle pain medications (NSAIDs, salicylates, steroids) is recognized Make it easy to do. Due to the duration of the barrier, up to about 24 hours before the future need is recognized, e.g. between about 1 hour to about 16 hours, about 2 hours to about 8 hours, or about 6 hours to about 10 hours, A barrier-forming composition may be administered. This increased time frame provides treatment options that were not previously possible.

  In one embodiment, a method for treating a body surface with an active agent comprises administering a therapeutically effective amount of a barrier-forming composition to the body surface, the barrier-forming composition for a duration of at least about 1 hour. A barrier coating having an effect of maintaining contact with the body surface is formed on the body surface.

  In one embodiment of the method, the step of administering the barrier-forming composition is performed in response to one of the following conditions: (a) identifying the future need for the active agent; and (b) Observation of events that cause future needs for active agents. In one embodiment, the administering step is performed in response to (a) or (b), and administering an initial barrier-forming composition to initiate a multiple dose regime that continues until the individual no longer needs the active agent; May be. In one embodiment, a second or subsequent therapeutically effective amount can be administered depending on the situation of (a) or (b). For example, the barrier-forming composition may be administered to a person when an observed event occurs, and administration of the barrier-forming composition continues at the above-described administration intervals until the individual leaves the vicinity of the contamination event. In another example, after a dosing schedule has begun, an individual may receive a second or subsequent dose when a new contamination event is observed, unless the dose occurs earlier than the shortest time of the stated dosing time interval. You may do it.

  In one embodiment, the observed event comprises a contamination event. Contamination events include, for example, an individual's sneezing, coughing, or vomiting, or more generally, when bodily fluids or substances emanating from the body adhere. Also included is the distribution of allergens in air or on the surface. In one embodiment, the contamination event is near the individual and elicits a dose response. Close to an individual may be defined as being within about 10 yards of the same room, vehicle, or individual.

  In one embodiment, the barrier-forming composition is applied to the mucosa of an individual at high risk. The mucosa may be the oral cavity, pharynx, or nasal mucosa. In one embodiment, the administering step is performed in response to contact with the environment that appears to be contaminated, or in response to confirmed contamination. The barrier-forming composition provides a barrier coating on the mucosa that sustains the activity of the active agent. In anti-allergen embodiments, the barrier-forming composition may prevent or prevent the allergen from moving onto the mucosa or causing a reaction.

  In another embodiment, the barrier-forming composition is administered in a method of treating a mammal suffering from damaged mucosa or skin lesions, such as an immune deficient mammal. The damaged site or lesion of the mammal is recognized and a therapeutically effective amount of the barrier-forming composition is administered at least to the damaged site of the mammalian mucosa. A barrier-forming composition having an antibacterial agent provides a barrier at the mucosal injury site that effectively inhibits active microorganisms from spreading to the mucosal injury site. Other active agents that are safe for application to open wounds may be included to promote healing.

  In one embodiment, a topical antimicrobial composition or barrier-forming composition having an antimicrobial agent or other active agent is used in a method of preventing infection. The step includes identifying a contaminated environment or contaminated item that the mammal is expected to contact. A contaminated environment is an indoor or outdoor space known or expected to be contaminated with harmful viruses, fungi, or bacterial microorganisms, or an environment such as the vicinity of a mammal or human. Determining whether a given environment is polluted is based on observations of public information about illnesses that are prevalent in the community, seasons, or other individuals who are suspected of being ill or are sneezing or otherwise spreading the pathogen . The latter factor can also be referred to as observation of contamination events.

  Predicting or identifying whether a contaminated environment or item will come into contact is a decision based on whether the mammal is planning or expected to enter the environment or touch the item in the near future Can do. This includes an estimate of the time to contact the contaminated environment or item. The composition at a time no greater than about 24 hours prior to the estimated contact time with the contaminated environment or item, such as no greater than about 16 hours, no greater than about 12 hours, no greater than about 6 hours, or no greater than about 2 hours before May be administered. The composition should be provided rapidly, eg within 1 minute of administration, eg within 30 seconds, and should be usable to prevent or inhibit infection of harmful microorganisms into the mucosa. As such, the composition may be applied while in contact with a contaminated environment or item to demonstrate effectiveness.

  In one embodiment, the topical antimicrobial composition is used to kill pathogens on mammalian skin. The composition may be applied by spraying, smearing or spreading on a topical surface such as the hand, arm, foot, leg, face, or genitals. In one embodiment, the composition is applied after a contaminated environment or contact with an item has been confirmed or suspected. In one embodiment, the composition is applied as a hand disinfectant daily or after meals, such as before meals or after toilet use. In one embodiment, the composition may be used prior to entering an environment in which no harmful microorganisms should be present, such as an operating room, or surgery, invasive physical therapy, childbirth, dental procedures, pre-operative cleaning, or wounding. It is applied to the skin before participating in activities such as treatment. In one embodiment, the skin surface is a predetermined surgical site. In one embodiment, the skin surface does not contain genital organs.

  In one embodiment, the compositions and methods of treatment and prevention described herein are useful for the prevention of infections in environments such as hospitals and infections commonly found in environments contaminated with such infectious microorganisms. obtain. As mentioned above, the methods and compositions described herein may be particularly adapted for immunocompromised patients or people who spend a lot of working time in a healthcare facility. The composition may also be useful in preventing infections caused by microorganisms that normally infect wounds.

  Contaminated environments include, for example, public transportation vehicles, public meeting places, rooms or vehicles containing mammals known or expected to be sick, or known to be sick or Probable mammalian neighborhood. For more information on the environment, such as aircraft, nurseries, and health centers that are generally recognized as contaminated environments, see Yang, et al. "Concentrations and Size Distributions of Airborne Influenza A Viruses Measured Indoors at a Health Centre, a Day-Care Center. , and on Aeroplanes, "JR Soc. Interface (Feb. 7, 2011), the contents of which are incorporated herein by reference.

  More specifically, in one embodiment, the public transport vehicle can be, for example, an aircraft, a bus, or a taxi. Examples of public meeting places include clinics, hospitals, schools, nurseries, churches, hotels, and restaurants. Examples of the vicinity of a mammal known or expected to be illness include, for example, within a radius of 1 foot (30.48 cm) of the mammal, or when riding in the car with the mammal. Public aircraft are a common and particularly noteworthy example of an environment often identified as a polluted environment. People who work for airlines, or who travel on public planes very frequently, such as 2-3 times a week, may be considered at high risk due to high exposure to microorganisms. it can.

  In one embodiment, for continuous administration for treatment or prevention, the barrier-forming composition is in divided doses as long as it is consistent with the predetermined dosage regimen of the particular active agent used in the barrier-forming composition. May be administered in a therapeutically effective amount. The continuous method of administration may be, for example, about once every 1-12 hours, once every about 2-8 hours, or once every about 4-6 hours. In another embodiment, a therapeutically effective amount of the barrier-forming composition is administered to the surface about every 2-12 hours, such as about every 3-8 hours, or about every 4-6 hours. “About every 2-12 hours” means that after a single therapeutically effective dose is administered, the next dose is administered after about 2 hours up to about 12 hours and additional doses are taken , Thereafter administered in units of about 2 hours up to about 12 hours. The topical antimicrobial composition may be applied at the same dose. The dosing regimen may be continued until no therapeutic effect is needed.

  In one embodiment, the barrier-forming composition is administered in a therapeutically effective amount three or more times within 24 hours, over a period of five 24 hours or more, e.g. 4 to 12 times, or 6 to 6 times. 10 doses over 6-10 days, or over 7-30 days. In another embodiment, the prophylactic method is continued for, for example, one day or more, such as from about 2 days to about 1 week. In another embodiment, three or more doses are administered only during sunshine hours or only when the individual is awake, e.g., 6 AM to 6 PM, or 9 PM to 5 PM. Also good. In one embodiment, the individual may follow a dosing regimen that provides protection throughout the workplace and other public gatherings. In one embodiment, the continuous administration method may be suitable when the subject is in prolonged contact with a contaminated environment or item.

  The body surface to be treated varies depending on the active agent in the barrier-forming composition. The mucosa to be treated may be the mucosal surface of the oral cavity, nasal cavity or larynx or pharyngeal cavity, for example nasopharynx (nasopharynx), oropharynx (pharynx) or pharynx (hypopharynx). Other mucous membranes of other openings in mammals may also be treated, including the vagina, anus, or ear canal. Skin or other body surfaces such as muscle pain, infections, wounds, acne, scalp, eyes, etc. may also be treated based on the active agent and its typical application site. In one embodiment, the composition is administered only to the skin, not to the mucosa, or not taken.

  In one embodiment, depending on the identification of the skin or mucosal lesion, the composition is administered to the skin or mucosal lesion. Subsequent doses are applied according to the dosing interval described above. In one embodiment, the dosing regimen is terminated when the lesion has healed, i.e., the lesion has been covered with new skin or mucosal tissue.

  In one embodiment, the barrier-forming composition captures and / or kills or neutralizes all harmful microorganisms that come into contact with the barrier-forming composition. In another embodiment, the barrier substantially captures and / or kills or neutralizes a sufficient amount of harmful microorganisms that come into contact with the barrier-forming composition to inhibit or prevent the microorganisms from causing infections. In the latter case, if harmful microorganisms are slow and / or weakened to penetrate the barrier, it enhances the body's own ability to prevent the microorganisms from causing disease or widespread infection. The addition of other active agents such as steroids can increase the effectiveness of barrier-forming compositions with antimicrobial agents. In topical antimicrobial compositions, it is not necessary that a barrier be formed for effective skin antimicrobial.

  In vitro tests have shown that embodiments of the barrier-forming composition allow all active bacteria to penetrate the barrier over an extended period of time, including about 2 hours or more, about 6 hours or more, about 16 hours or more, about 24 hours or more. Proved to prevent. In vitro studies have shown that viruses exposed to embodiments of the barrier-forming composition can be prevented from growing for about 2 days or more (such as influenza) to about 9 days or more (such as HIV), and the number of viruses thereafter For example, it has been shown to be below the MIC for an extended period of about 2-3 days. Inhibitory activity against influenza virus was observed for up to 48 hours.

  The barrier-forming composition has shown activity in clinical trials to reduce human microbial load. For example, from about 1 to about 6 hours after the administration step, a surprisingly effective microbial load reduction of about 50% to about 99% has been demonstrated. In embodiments, the microbial load may decrease by more than about 10%, more than about 25%, or more than about 70% after about 1 to about 6 hours of the administering step. Moreover, these reduced ranges of microbial load can be sustained over time with the disclosed regimen.

  FIG. 1A is a flowchart showing microorganisms in contact with an untreated skin surface (left) and a skin surface (right) on which a coating layer has been formed as a result of administration of the coating composition. The main effectiveness of is shown. Instead of protecting the mucosa from microbial infection, when treated on the skin surface, the coating layer kills the microorganisms on the surface, allowing the microorganisms to bind to the surface, form colonies, and form a biofilm To prevent. Biofilm destruction is known to be difficult. Thus, the coating composition provides a surprisingly effective disinfecting skin surface solution compared to detergents that focus only on the rapid and short-term killing of only the microorganisms already on the surface. While antibacterial solutions that do not form a barrier coating instantly kill some of the microorganisms in the biofilm on the surface, it is virtually impossible to kill all the microorganisms in the biofilm, Start forming colonies again. In one embodiment, the coating composition also has long-term activity that first prevents the biofilm from forming and destroys the already formed biofilm. Low tack embodiments of the coating composition may not be as robust as preventing passage of microorganisms, like other embodiments with more wetting agents and carbohydrate gums, but kill or neutralize microorganisms Have been found to be effective and have potent activity against MRSA and Candida.

  In one embodiment showing the proposed mechanism of the barrier-forming composition shown in FIG. 1, the barrier-forming composition provides antiviral activity. When the virus contacts the cell, it binds to a receptor on the host cell. After 5-6 hours, the virus is taken up by the host cell, grows in the host cell, and induces cell lysis that generates additional virus particles that infect other host cells.

  In contrast, in cells treated with the barrier-forming composition, the protective barrier is on the surface of the host cell. The barrier is thick enough to cover the cell and the receptor on the cell and prevent the virus particles from binding to the cell receptor. This prevents infection and lysis. The barrier-forming composition retains the barrier for a long duration of about 1 hour or more, about 2 hours or more, about 6 hours or more, about 16 hours or more, about 16 hours to about 24 hours, or about 24 hours or more, and Protects host cells and prevents infection. The bactericidal or bacteriostatic action is also maintained for a long duration of about 2 hours or more, about 6 hours or more, about 16 hours or more, about 24 hours or more, or about 48 hours or more, thereby killing the microorganism, Reduce load. These durations apply to viruses, bacteria, and fungi.

  Harmful microorganisms are known to cause infections such as infectious diseases caused by microorganisms, such as the following genus Candida (eg C. albicans), C. glabrata (Candida glabrata) ), C. krusei (Candida crusei), C. tropicalis (Candida tropicalis, etc.), staphylococcal species (including methicillin-resistant Staphylococcus aureus, MRSA), streptococcal species (eg S. sanguis (Streptococcus sanguis) ), S. oralis (Streptococcus oralis), S. mitis (Streptococcus mitis), S. salivarius s (Streptococcus sarivarius), S. gordonii (Streptococcus gordonii), S. pneumoniae (Acne pneumoniae)・ Baumani, Aggregate Bactor ・ Actinomistem Comitans, Fuzo Microorganisms such as bacteria nucleatum, other microorganisms that cause upper respiratory tract infections or colds (rhinovirus), and influenza viruses, and Pneumonia, Porphyromonas gingivalis, Yersinia enterocolitica, Acinetobacter baumanni, Aggregatebacter Actinomycetemcomitans, microorganisms that cause odors, microorganisms that impair the appearance of the surface, Clostridium difficile, Bordetella pertussis, Burkholderia, Aspergillus fumigatus, Penicillium, Cladosporium, Klebsiella pneumoniae, Hog cholera, In Escherichia coli (O157: H7), Trichodermatosis, rhinovirus type 39, RS virus, poliovirus type 1, rotavirus Wa strain, influenza A virus, herpes simplex virus types 1 and 2, and hepatitis A virus That. In one embodiment, the barrier-forming compositions and methods of treatment and prevention described herein include, for example, sexually transmitted diseases such as infections caused by human immunodeficiency virus (HIV), herpes simplex or human papillomavirus (HPV), etc. ) May be useful in preventing infections caused by

  Most of the above microbial species have been tested and found to be effectively suppressed or killed by the barrier-forming composition. Further, the barrier-forming composition can be, for example, about 30 nm or more, such as about 100 nm (HIV; sphere), about 100 nm to about 300 nm (influenza; elongated sphere), about 120 nm to about 260 nm (EBV; sphere / disk), about 30 nm. Efficacy was demonstrated against microorganisms having a (rhinovirus; spherical) diameter. Thus, the barrier composition will have efficacy against other microorganisms having a diameter of about 30 nm or greater than about 30 nm.

  The composition exhibited even potent and remarkable inhibitory activity on biofilms that are fairly difficult to eradicate. In one embodiment, the method of the present application comprises administering the barrier-forming composition to a biofilm formed on the mucosa or lesion.

  The microorganism may be an airborne microorganism. In one embodiment, the microorganism is one that causes an infectious disease. In one embodiment, microorganisms do not include those that cause allergic reactions or dental diseases such as caries, gingivitis, or seasonal allergies. Similarly, in one embodiment, the prevention method does not prevent dental disease or allergic reactions, such as caries, gingivitis, or seasonal allergies, alone or in addition.

  However, in another embodiment, microorganisms such as fungi, which are generally classified as allergens, other allergens, and mucosal irritants in the air are blocked by the barrier-forming compositions and methods of the present application.

The therapeutically effective amount of the entire barrier composition, including the active agent, is sufficient to cover the target mucosa or lesion with a barrier-forming composition that forms a barrier coating that forms a barrier layer on the mucosa or lesion. Is included. For example, from about 100 μL to about 10 mL for mouthwash formulations, such as from about 1 mL to about 8 mL, from about 2 mL to about 5 mL, and from about 0.125 mL to about 2 mL, such as from about 0.5 mL to about 1 mL, for spray formulations. The dose can be expressed in terms of volume per square centimeter, for example about 0.5 μL / cm ² to about 50 μL / cm ² , for example about 5 μL / cm ² to about 40 μL / cm ² or about 10 μL / cm ² for mouthwash formulations. to about 25 [mu] L / cm ^2, or in a spray formulation about 0.625μL / cm ² ~ about 10 [mu] L / cm ^2, can be, for example, about 2.5 [mu] L / cm ² to about 5 [mu] L / cm ^2. Other delivery vehicles such as dissolvable strips can have dosages derived from these ranges, adjusting the concentration and other factors known to those of skill in the art. Also, the average thickness of the thin film formed on the mucosa from the barrier-forming composition can range, for example, from about 0.001 mm to about 0.2 mm, such as from about 0.01 mm to about 0.1 mm, or from about 0.08 mm to about 0.15 mm. . For example, for a given human or animal, a therapeutically effective amount can be determined based on the age or weight or size of the mammal to be treated, and the dosage can be as described above. Particularly in the case of non-human mammals, the dosage can be adjusted according to the values per square centimeter described above and the approximate surface area of the mucosal surface or body cavity of the treated subject. The topical antimicrobial composition may be applied to the skin surface in the same amount.

  Other delivery vehicles such as the composition, liquid-filled lozenges or roll-on applicators, or treated rubbed materials derived from these ranges, adjusting concentrations and other factors known to those skilled in the art Can have a dosage.

  The average thickness of the thin film or coating formed on the mucosa, skin, or skin lesion surface from the barrier-forming composition is, for example, from about 0.001 mm to about 0.2 mm, such as from about 0.01 mm to about 0.1 mm, or from about 0.08 mm to about It can be in the range of 0.15 mm.

Mechanical action pump spray devices or aerosolized spray devices may be used. In embodiments of aerosolization, the barrier-forming composition, CO _2, nitrogen, and may be mixed with common propellants, such as hydrocarbons. However, bag-on-valve embodiments may also be used, and the composition is sufficiently stable that separation of the propellant and composition components is not required.

  As shown in the examples below, the barrier-forming compositions of the present invention have been shown to block and trap a wide variety of representative fungi, bacteria and viruses to kill or neutralize them.

  Several experiments were performed to evaluate the safety of the composition for mammals and the ability of the spray formulation to form a protective barrier on the engineered human oral mucosa (EHOM) model and pig skin. Experimental evidence has shown that the compositions of the present invention form a barrier coating on the tissue and skin, which prevents microbial invasion into the tissue and provides a long-lasting coating.

(Experiment 1)
<Culture of human gingival epithelial cells and fibroblasts>

  Normal human gingival cells (epithelial cells and fibroblasts) were obtained from ScienCell Laboratories (Carlsbad, CA). Fibroblasts were cultured in Dulbecco's modified Eagle medium (DME; Invitrogen Life Technologies (Burlington, Ontario, Canada)) supplemented with fetal bovine serum (FBS; Gibco (Burlington, Ontario, Canada)) to a final concentration of 10%. Epithelial cells are cultured in Dulbecco's Modified Eagle Medium (DME) / Ham's F12 (3: 1) (DMEH) supplemented with 5 μg / mL human transferrin and 2 nM 3,3 ′, 5′-triiodo-L-thyronine did.

In Dulbecco's Modified Eagle (DME) / Ham's F12 (3: 1) (DMEH) medium supplemented with 0.4 μg / mL hydrocortisone, 10 ng / mL epidermal growth factor, penicillin and streptomycin, and 10% FBS (final concentration) Cultured. This medium was changed once a day for epithelial cells and three times a week for fibroblasts. When the culture reaches 90% confluence, the cells are detached from the flask using 0.05% trypsin-0.1% ethylenediaminetetraacetic acid (EDTA) solution, washed twice and DMEM (for epithelial cells) Alternatively, it was resuspended in a medium supplemented with DMEH (in the case of fibroblasts).
(Experimental example 2)
<Operating human oral mucosa (EHOM) tissue>

  The EHOM model was created using the gingival fibroblasts used to form a complex three-dimensional spatial cell configuration similar to that found in normal human oral mucosa and the epithelial cells of Experimental Example 1. The lamina propria was prepared by mixing type I collagen (Gibco-Invitrogen (Burlington, Ontario, Canada)) with gingival fibroblasts and cultured in a medium supplemented with 10% FBS for 4 days. Subsequently, EHOM was obtained by seeding gingival epithelial cells in this lamina propria. Tissue specimens were grown under immersion conditions until the entire surface of the lamina propria was covered with epithelial cells. To generate stratified epithelium, EHOM was raised to the gas-liquid interface for an additional 4 days to promote the organization of the epithelium into another layer.

The lamina propria is a thin layer of loose connective tissue that is subepithelial and forms the mucosa with the epithelium. FIG. 2 is an EHOM mucosal tissue diagram showing the position in the mucosa covered with the coating composition with arrows.
(Experimental examples 3 to 9)
[158] Examples 3-9

  Each example of the coating composition was made by adding the following ingredients to a 50 mL centrifuge tube and vortexing to a “free flowing” concentration. The components of each composition and their approximate amounts are listed in Table I (values in Table I are weight percentages in the total composition).

From the following results, it was found that preservatives are unnecessary for barrier coating formation and antibacterial activity.
(Experimental examples 10-26)

In order to demonstrate the safety of the composition on the mucosal surface, Experimental Examples 10 to 26 were conducted. Prior US Patent Publication No. 2012/0270909 and the provisional application to which this application claims priority benefit include this information.
(Experimental examples 27 and 28)
<Determining whether the coating composition affects the mechanical barrier function of EHOM against microorganisms that pass through mucosal tissue>

  In Experimental Examples 27 and 28, two approaches were used to determine if the Control Example formed a barrier coating that blocked microorganisms that passed through mucosal tissue and also had an inherent antimicrobial effect. Growth in the pass-through chamber and on the EHOM surface was assessed by growth assessment in agar.

In Experimental Example 27, EHOM of Experimental Example 2 was placed in the 1% and 5% dilutions of Experimental Example 4 (diluted with serum-free medium) and contacted for 2 minutes. The tissue was then washed twice with serum-free medium and then overlaid with 300 μL of 1 × 10 ⁶ Candida cells. The tissue was then placed on an air-liquid culture plate and incubated for 24 hours at 37 ° C. in a 5% CO ₂ humidified atmosphere. Next, the culture medium under EHOM (ventral chamber) was collected and seeded on a Sabouraud agar plate, and it was confirmed whether or not the microorganisms penetrated the tissue and reached the following culture medium. Cultures were also collected from the EHOM surface and seeded on Sabouraud agar plates. This process is illustrated in FIG.

  In Experimental Example 28, the EHOM of Experimental Example 2 treated for 2 minutes with the 1% and 5% dilutions of the composition of Experimental Example 4 was covered with Candida cells for 24 hours and placed upside down on a Sabouraud dextrose agar plate. Left in position for 5 minutes. The EHOM was then removed and the plates were incubated at 30 ° C. for 24 hours, after which the growth of microorganisms was confirmed with the naked eye and photographed. Each experiment was repeated 5 times with similar results.

FIG. 4 shows the results of the culture of the EHOM plane (panels C and D) and the culture of the pass-through solution in the bottom (ventral) chamber (panels A and B). Panels A and C are EHOM treated with the 1% dilution of Experimental Example 4, and Panels B and D are EHOMS treated with the 5% dilution of Experimental Example 4. From these data, it was shown that the barrier coating formed by the composition of Experimental Example 4 prevents penetration of EHOM tissue by microorganisms, but does not have an inherent antibacterial effect.
(Experimental Examples 29 and 30)

Experimental Examples 29 and 30 are repetitions of Experimental Examples 27 and 28 except that EHOM was infected with S. mutans. Similar results were obtained indicating that the coating composition formed a barrier coating that prevented S. mutans microorganisms from passing through the barrier coating but did not have an antimicrobial effect.
(Experimental examples 31 and 32)
<Determining whether the coating composition affects the mechanical barrier function of EHOM against microbial invasion>

  In Experimental Example 32, the EHOM tissue set of Experimental Example 2 was treated with the coating composition of Experimental Example 4 and then overlaid with C. albicans. In Control Example 31, the control set was not treated with the coating composition before it was overlaid with C. albicans. Immediately after each contact time, biopsies were collected from each EHOM, fixed with paraformaldehyde solution, and embedded in paraffin. Thin sections (4 μm) were stained with eosin hematoxylin. Sections were observed using an optical microscope and analyzed for infiltration / penetration of microbial cells in the tissue. After microscopic observation, representative photographs of each condition were taken and presented. This experiment was repeated three times with similar results. Similar results were obtained with the treatment according to Experimental Example 3 (data not shown).

FIG. 5 shows the effect of the coating composition on microbial invasion of EHOM tissue. Panel (A) is a representative photograph of untreated control example 31, and panel (B) is a photograph of treated experimental example 32. The arrow indicates the invading mycelium in the untreated control example 31.
(Experimental Examples 33 to 40)

  The above-mentioned EHOM model was also used to evaluate the barrier film forming ability of Experimental Examples 5-7. The ability to form a barrier coating is (a) preventing oral bacteria (S. mutans) and fungi (Candida albicans) from entering / penetrating the human oral mucosa, and (b) not damaging host cells. (Cytotoxicity assay).

  Experimental Examples 33-40 were prepared according to Table II.

  In Experimental Examples 33 to 40, after pretreatment and incubation according to the procedures of Experimental Examples 27 and 28, (1) collect the flow-through medium from the lower chamber, and (2) flip it over the surface of the Sabouraud dextrose agar petri dish. Incubated for 24 hours. As described in Experimental Examples 27 and 28, the collected flow-through medium was spread on an agar plate and incubated for 24 hours. Also shown in Table II are reference figure numbers that carry photographs of each experimental example showing the growth of microorganisms on the culture of each experimental example turned inside out.

FIGS. 6 and 7 show that both Candida and Streptococcus were able to grow on the surface of EHOM treated with the compositions of Experimental Examples 5-6. In contrast, as shown in FIG. 8, no microbial growth was observed in the “flow-through” medium collected from the lower chamber of EHOM in Example 36 or 40, ie, the medium treated with the composition of Example 7. It was. This indicates that even when EHOM was treated with the composition of Experimental Example 7, damage to the surface of the mucosal tissue did not occur, and the organism could not penetrate into the treated EHOM. Similar results were obtained with EHOM treated with the compositions of Experimental Examples 5 and 6 (data not shown). These data indicate that the combination of glycerin and xanthan gum can form a protective barrier coating on mucosal tissue.
(Experimental examples 41 to 47)
<The test preparation is non-toxic and will not damage cells / tissues>

  In Experimental Examples 41-47, the toxicity of the composition was evaluated using the EHOM model. Experimental Examples 41-47 were prepared according to Table III.

  After pretreatment and incubation according to the procedures of Experimental Examples 27 and 28, the culture supernatant was collected from the EHOM tissues of Examples 41 to 48 and used for the measurement of LDH activity.

  As shown in Figure 9, in Experimental Examples 41-48, regardless of whether the formulation contains cetylpyridinium chloride with or without preservatives and whether it was infected with either Candida albicans or S. mutans No significant increase in LDH levels was observed. These data showed the non-toxic effects of the experimental coating compositions and also demonstrated that these formulations maintain the integrity of the host mucosal tissue.

  Data are mean ± SD. There was no significant difference between untreated and treated tissues.

In summary, the above data showed that the composition of the experimental example presents an effective and safe barrier capable of preventing microorganisms penetrating through human mucosal tissue.
(Experimental Examples 48-61)

  Preclinical evaluation of the coating composition has shown that the composition is effective against many bacteria and yeasts. S. salivarius, P. gingivalis, S. pyogenes, S. pneumonia, Fusobacterium nucleatum, S. mutans, S. aureus, Y. enterocolitica, S. oralis, S. mitis, C. albicans, C. krusei, C. tropicalis The antimicrobial activity of the coating composition of Experimental Example 7 was evaluated against multiple clinical isolates obtained from patients, including C. glabrata. The activity of the coating composition of Example 7 was determined using the standard method described in the clinical and laboratory standards association (CLSI) document numbers M07-A8, M11-A7 and M27-A3 using the minimum inhibitory concentration (MIC ) Was evaluated.

Standardized inoculum of several types of aerobic or anaerobic bacteria (1 × 10 ⁴ cells / mL), as a comparative example, a serially diluted solution of experimental example 7 (containing 0.1% or 1 μg / mL CPC) or 2 Incubated with% chlorhexidine gluconate (CHX, 20 μg / mL). Cells were grown for 24 hours in the presence or absence of test agents (growth control). The MIC for each agent was defined as the concentration that induced 100% growth inhibition (compared to the drug-free control).

  A similar microdilution based CLSI method (M27-A2) was used to evaluate the activity of Example 7 against albicans and non-albicans Candida species.

  The coating composition was also found to have potent antimicrobial activity against MRSA, Acinetobacter baumannii, Streptococcus sanguis, S. gordonii, and Aggregatibacter actinomycetemcomitans.

  As can be seen from Table IV, the composition of Experimental Example 7 showed strong activity against many aerobic and anaerobic bacteria and fungi.

  The MIC of the coating composition of Example 7 against S. oralis and S. mitis was significantly increased (500 μg / mL) compared to other organisms. It is interesting that S. oralis and S. mitis are normal commensals of the oral cavity. The activity of commonly used antibacterial chlorhexidine (2% solution) was also determined by the same method. Table IV shows the MIC of the coating composition of Example 7 and chlorhexidine (2% solution) as comparative examples for various microorganisms.

  In summary, these results demonstrated that Experimental Example 7 generally has a strong activity against pathogenic bacteria and fungi isolated from the oral cavity. This activity was more potent than that observed with chlorhexidine.

Similar activity profiles were observed for the coating compositions of Experimental Examples 10 and 11.
(Experimental example 62)

As a further comparison, from published data, the coating compositions tested show superior or at least equivalent MICs in the CPC alone comparison (ie, not in the compositions with the barrier coating formulations disclosed herein). (See Frank-Albert Pitten and Axel Kramer, “Efficacy of Cetylpyridinium Chloride Used as Oropharyngeal Antiseptic,” Arzneim. Forsch./Drug Res. 51 (II), pp588-595 (2001). The contents of which are incorporated herein by reference). The data varies depending on the test microorganism, but for example, the MIC of CPC (single) against S. mutans is 5.0 μg / mL to 6.25 μg / mL, which is higher than the 1.95 μg / mL reported in Example 53. Will be less effective. This was an unexpected result in light of the risk that CPC loses its activity when mixed with other excipients in the formulation. Department of Health and Human Services (Food and Drug Administration) (1994) Oral Health Care Drug Products for Over-the-Counter Human Use; Tentative Final Monograph for Oral Antiseptic Drug Products.Proposed Rules (21 CFR Part 356, Docket No 81N-033A, RIN 0905-AA06). See Federal Register 59: 6084-124.
(Experimental Examples 63-69)
<In vitro antibacterial activity duration of coating composition: Post antibacterial effect (PAE) assessment>

  The PAE of Experimental Example 8 for several microorganisms was evaluated in Experimental Examples 63-68. A control example 69 was also prepared. Some microorganisms were exposed to Example 8 (at a concentration equal to MIC) for 1 minute and then washed 3 times to remove residual formulation. The treated cells were then spread on agar plates incubated at 37 ° C. and the time required for cell regrowth was measured. The PAE was expressed as the time (hour) during which the growth inhibition rate (%) was maintained by Experimental Examples 63-68, compared with the untreated Control Example 69.

As shown in FIG. 10, Experimental Example 8 is a 4 to 24 hour period depending on the organism tested (S. aureus, S. pneumonia, S. gordonii, S. sanguis, S. salivarius, and S. mitis). In between showed PAE. The same activity as in Experimental Example 8 was observed against Candida (data not shown). The coating compositions of the other experimental examples showed similar PAE against microorganisms.
(Experimental example 70)

From the PAE test of the coating composition against S. mutans of Experimental Example 7, compared with a similar comparative example in which the CPC content was reduced to 0.7%, the PAE of Experimental Example 7 was compared to 6 hours of Comparative Experimental Example 70. It was shown to be 24 hours. Therefore, it was proved that Experimental Example 7 showed antibacterial activity for a longer time than Comparative Experimental Example 70, and that the addition of the CPC content exhibited more than a mere additive effect on the antibacterial activity.
(Experimental examples 71-76)

  Treatment with the composition of S. sanguis (Experiment 71), S. oralis (Experiment 72) and C. albicans (Experiment 73) using the scanning electron microscope impairs cell integrity. It has been shown.

  In Experimental Examples 71-73, cells were grown for 24 hours in the presence of Experimental Example 3. The cells were then washed to remove residual formulation, dehydrated through a series of alcohol solutions (10% -100% (v / v)) and processed for SEM analysis. Control examples 74-76 differ from experimental examples 71-73 in that they were not grown in the presence of experimental example 3.

Unlike untreated control examples 74-76, which were proven to be healthy and intact cells (FIGS. 11A, 11C, and 11E) from SEM photographs, microorganisms exposed to the coating composition of Experimental Example 3 Deformation, collapse, and complete destruction of cell integrity were shown (Figure 11B, Figure 11D, Figure 11F), with clear evidence of cytoplasmic material leakage.
(Experimental examples 77-79)

  Since biofilm is a precursor of specific infectious diseases in Experimental Examples 77 to 79, an experiment was conducted to determine whether the coating composition can prevent the formation of biofilm by bacteria and yeast. Biofilms were formed using an in vitro model. For details of in vitro models, see Chandra et al. “In vitro Growth and Analysis of Candida Biofilms” Nature Protocols 3 (12): 1909-1924 (2008).

  In Experimental Examples 77-79, a standard biofilm model was utilized to determine whether the coating composition of Experimental Example 3 was active against bacterial and fungal biofilms. In Experimental Examples 77 to 79, three types of microorganisms (C. albicans, S. oralis, S. salivarius) were adhered to the substrate for 90 minutes to form a biofilm in the adhesive phase. Next, the disc containing the adherent bacteria was incubated for 15 minutes, 30 minutes or 60 minutes in 50% concentration of Example 3 (diluted 1: 1 with an appropriate medium). After incubation, the biofilm was detached, spread on the culture medium and incubated to determine colony forming units (CFU). Medium diluted with phosphate buffered saline (PBS (1: 1)) was used as a control. Table V shows the data at 0 minutes (control), 15 minutes, 30 minutes and 60 minutes.

Data for Experimental Examples 77-79 are also shown in FIG. 12 as a graph of inhibition rate versus growth control. These results show that the coating composition of Experimental Example 3 inhibits bacterial and fungal microorganisms with a MIC of 0.2% against biofilms formed by S. salivarius, S. oralis or C. albicans. It was.
(Experimental examples 80 and 81)

In Experimental Example 80, the present inventors evaluated the effect of exposing a C. albicans early stage biofilm to Experimental Example 3 for 1 minute. It was found that film formation can be inhibited (FIG. 13). Experimental Example 81 was an untreated control sample.
(Experimental examples 82 and 84)
<Processing capacity of mature biofilm by coating composition>

  In order to determine whether the coating composition is capable of processing biofilms, we evaluated the activity of the barrier-forming composition against fully formed mature biofilms. The biofilm was grown to maturity and then exposed to Example 7 for 2 or 4 hours, and the resulting CFU was determined. Compositions that reduce microbial CFU by at least 2 log reduction compared to untreated cells are considered effective against microbial biofilms.

  As shown in Table VI, the biofilm formed by C. albicans and S. oralis was completely removed by exposure to Experimental Example 7, and the CFU of the biofilm formed by S. salivarius was compared to the untreated control. Reduced by 3.4 log reduction (log CFU was 3.95 vs 7.36, respectively).

In summary, the above results indicate that Experimental Example 7 has potent activity against biofilms formed by bacteria and fungi.
(Experimental examples 85-86)
<The coating composition is also active against viruses>

  The activity of the coating composition against viruses such as respiratory viruses (influenza virus H1N1, strain 2009 / H1N1 / infA) and human immunodeficiency virus (HIV) was measured.

  The coating composition inhibits influenza A infectivity.

  To assess the effect of the coating composition on the infectivity of influenza virus, madin derby canine kidney (MDCK) cells were grown to ≧ 90% confluent at 37 ° C. prior to infection. MDCK cells are routinely used for assays involving influenza virus.

  In Experimental Example 85, the cell monolayer was exposed to the coating composition of Experimental Example 7. In Control 86, the cell layer was exposed to OptiMEM (+ P / S, + Lglu) tissue culture medium for different times: (1) T1: 30 minutes exposure, (2) T2: 1 hour exposure, (3) T3: 2 hours exposure. The formulation was then removed and the cell monolayer was infected with influenza virus (multiplicity of infection (MOI) = 0.1). Untreated cells or cells infected immediately after exposure (T0) were used as baseline controls. The infected cells were then centrifuged, resuspended in 500 μL growth medium and incubated at 32.5 ° C. for 48 hours. Moreover, the influence of the coating composition of Experimental Example 7 on the infectivity of influenza virus to mammalian cells was also evaluated using an immunofluorescence microscope (using FITC-labeled anti-influenza antibody).

  FIG. 14 shows the influence of Experimental Example 7 on the cytopathic effect of MDCK cells infected with influenza (Experimental Example 85) (Panels A and C) and Control Example 86 (Panels B and D). Images were obtained from: Phase contrast (A-B) and immunofluorescence microscopy (C-D): No specific cytopathic effect (CPE) was observed in cells treated with the formulation. Untreated cells exhibited typical CPE with local rounding and degenerative changes.

  These data indicated that the cell monolayer remained confluent and healthy (Experiment 85) even after exposure to Experiment 7 for 30 minutes, 1 hour or 2 hours. In contrast, untreated cells and cells treated just before infection (T0) (control example 86) showed a substantial cytopathic effect. As shown in panel C of FIG. 14, fluorescence was shown in the untreated cells of Experimental Example 86 (FIG. 14, Panel D), but no fluorescence was observed in the cells treated with the coating composition of Experimental Example 85. It was.

Further fluorescence microscopic images corresponding to Experimental Examples 85 and 86 are shown in FIG.
(Experimental examples 87 and 88)
<Activity of coating composition against viral load using quantitative PCR>

  FIG. 16 shows influenza virus levels in infected treated cells (Experiment 87) and untreated cells (Experiment 88) as determined by quantitative PCR. In Experimental Example 87, the cells were treated in Experimental Example 7, and in Control Example 88, the cells were left untreated. Thereafter, the supernatant was collected and analyzed for the presence of virus.

  The cell culture supernatant was collected from the same assay as in Experimental Examples 87 and 88, and nucleic acid was extracted using a QIAamp virus RNA kit (QIAGEN (Valencia, Calif.)). Random Hexamer Primers (Invitrogen (Carlsbad, Calif.)) Was used to create a cDNA library for each sample. The reverse transcription reaction was performed using M-MLV RT according to the manufacturer's specifications (Invitrogen, Carlsbad, CA). Quantitative analysis was performed on StepOne Plus Taqman Real Time PCR (Applied Biosystems (Branchburg, NJ)), TaqMan Universal PCR Master Mix (Applied Biosystems (Branchburg, NJ)), 2 μL cDNA sample, and primers / probes. Used to target the influenza matrix gene. Reference standards were prepared using a conventional RT-PCR, H1N1 matrix gene amplified by a purified gel (QIAquick, Qiagen, Valencia, Calif.) And a cDNA fragment of human RNAse P, and a spectrophotometer (Beckman Coulter Quantitation using a company (Blair, CA).

  As shown in FIG. 16 and Table VII, the cells of Experimental Example 87 treated for 30 minutes or 60 minutes in Experimental Example 7 did not have detectable influenza 48 hours after infection. Furthermore, as a result of the treatment for 2 hours in Experimental Example 7, the viral load was reduced to 1/6 compared to the untreated control or the sample treated immediately before infection (Experimental Example 88).

(Experimental examples 89-91)
<The coating composition has a direct antiviral effect against influenza virus>

  To determine if the coating composition has direct antiviral activity against influenza virus, we have grown in a 24-well plate to viral African green monkey kidney (CV-1) cells (90% confluent). Were infected with influenza pretreated in Experimental Example 7. CV-1 cells are a highly sensitive substrate used routinely for diagnostic and viral studies.

  In Experimental Examples 89-91, standardized amount of influenza virus (0.1 MOI) for 5 minutes at room temperature, (1) Experimental Example 7 (to form Experimental Example 89), (2) Control Example 6, CPC-free preservative Pre-treated with compound with agent (to form Experimental Example 90), (3) placebo alone from Control Example 5 (compound without CPC and preservative) (to form Experimental Example 91). After a 5 minute incubation, the virus / drug mixture was diluted with OptiMEM (+ P / S, + Lglu) by an additional homologous volume to dilute the treatment composition.

  In Experimental Examples 89-91, CV-1 cells were prepared as described above. The cells treated and untreated in Experimental Examples 89-91 were then inoculated into the cells as described above.

  Influenza virus load was determined by real-time PCR as described above. From the data shown in FIG. 17, the influenza virus pretreated with the coating composition of Experimental Example 7 containing the antibacterial agent CPC (Experimental Example 89) contains the coating composition and / or preservative but does not contain CPC ( Compared with Experimental Examples 90 and 91), a significant reduction in viral load was shown. Virus pretreatment according to Experimental Example 7 showed a significant reduction in virus copy compared to the formulation without CPC.

These results demonstrate that the coating composition of Example 7 has direct antiviral activity against influenza viruses that are not unique to Examples 5 and 6.
(Experimental examples 92 and 93)

In Experimental Examples 92 and 93, the ability of the coating composition to inhibit influenza A (2009 / H1N1 / infA) infection was tested. African green monkey kidney (CV-1) cells were grown to 90% confluence in 24-well plates. Next, the coating composition of Experimental Example 7 was applied to the cells of Experimental Example 92 (20% Experimental Example 7, 80% OptiMem, working CPC concentration 0.02%). Each time point is consistent with Control 93 (no coating composition applied, 100% OptiMem). The coating composition was allowed to stay on the surface for 30 minutes and then removed from the cell monolayer. Cells were washed thoroughly twice with sterile optiMEM (+ PfS, + Lglu). Influenza was inoculated at an MOI = 0.1 from T0 to T + 6 hours at 30 minute intervals. After infection, the cells were centrifuged for 30 minutes at 2200 rpm with 500 μL optiMEM (+ P / S, + Lglu, 2 μg / mL trypsin (sigma-Aldrich, St. Louis, Mo.). Grow for 5 hours with 5% CO _2. Influenza virus load was determined by real-time PCR.

  As shown in FIG. 18, pretreatment of the host monolayer with a glycerin-xanthan gum formulation inhibited viral infection by up to 84.93% compared to untreated controls. The fact that inhibition of viral infection was observed in the host cells despite the removal of the coating composition was due to the fact that the coating composition formed a protective barrier coating on the host cells that prevented virus entry for at least 6 hours. Show.

FIG. 1B can be referred to as a possible mechanism to address the inhibition of infection.
(Experimental Examples 94-96)
<The coating composition exhibits activity against HIV>

  In Experimental Examples 94 to 96, it was determined whether the coating composition had activity against HIV. Host MT mammalian cells were seeded in 96 well round bottom plates at a density of 15,000 cells / well in RPMI / 10% FBS / PS. The next day (Day 2), cells were pretreated for 5 minutes in Control Example 5 (Forming Experimental Example 94), Control Example 6 (Forming Experimental Example 95), or Experimental Example 7 (Forming Experimental Example 96). Added to. 24 hours after exposure to the formulation, MT (Macaque) mammalian cells were washed 3 times with phosphate buffered saline (PBS) and replaced with fresh medium. On day 1, day 2, day 5, day 6, day 7 and day 9, the supernatant (10 μL) after treatment was collected, and the viral load was measured by reverse transcriptase (RT) activity. . FIG. 19 shows a graph of virus copy per mL for each experimental example 72-74 over 9 days.

  The illustrated results indicate that Experimental Example 7 in Experimental Example 96 exhibited anti-HIV activity at all monitoring time points after treatment.

  Control Example 5 or Control Example 6 without CPC and / or preservative in Experimental Examples 94 and 95 showed the least anti-HIV activity.

In summary, our findings demonstrate that Experimental Example 7 of a coating composition containing CPC exhibits long-lasting antiviral activity against HIV.
(Experimental Example 97)

  Representative bioviral lesions are important infections in various mucosal tissues. In Experimental Example 97, an experiment was performed to determine whether the coating composition exhibited activity against general oral Epstein-Barr virus (EBV). Western blotting was used to evaluate the resolution of the lytic virus protein EAD (indicating inhibition of virus replication) by the coating composition of Experimental Example 8.

In Example 97, gastric epithelial cells infected with EBV were exposed to different dilutions (1:16, 1:32, 1:64) from Example 8 and specific antibodies were used to detect the presence of EAD protein. did. The presence of cellular β-actin was used as an index of epithelial cell integrity. As shown in FIG. 20, the 1:64 dilution of Experimental Example 8 degraded EAD without affecting cellular actin. These results demonstrate that Experimental Example 8 inherently inhibits viral replication and is therefore an effective antiviral and useful in preventing viral infection.
(Experimental examples 98-100)
<Durability of antibacterial barrier versus commercial mouthwash>

  In order to determine the duration that the coating composition can maintain antimicrobial activity, bacteria and fungi were treated with EHOM of Experimental Example 2 treated with the coating composition of Experimental Example 7 in a well, with an equivalent commercial product. It was exposed to EHOM of Experimental Example 2 for 2 minutes. Bacteria and fungal microorganisms were layered on untreated control EHOM (Experimental Example 98) and treated EHOM (Experimental Example 99 and Comparative Example 100). The residual (flow-through) solution was then removed from the well bottom (lower chamber of the EHOM model) and spread on an agar plate. Figure 3 further clarifies this test method. These plates were incubated at 37 ° C. and the number of proliferating microbial cells (colony forming units; CFU) after 24 hours was counted.

  Control 98 tested untreated EHOM. In Experimental Example 99, S. mitis bacteria were overlaid on the coating composition as described above. Experimental Example 100 is a comparative example showing the activity of commercially available LISTERINE (including ethanol (26.9%), menthol, thymol, methyl salicylate and eucalyptol) against S. mitis bacteria. The results are shown in Table VIII.

(Experimental examples 101-103)

  In Experimental Examples 101-103, the same procedure as in Experimental Examples 98-100 was performed, except that Candida albicans bacteria were tested with the coating composition as described above. The results are shown in Table IX. Experimental Example 103 is a comparative example showing the activity of commercially available LISTERINE.

These data further indicate that the coating composition of Example 7 maintains activity including up to 24 hours. In summary, these results indicate that, unlike LISTERINE, the coating composition of Example 7 continued to maintain an intact barrier to EHOM tissue for up to 24 hours.
(Experimental examples 104-153)

  Experimental examples 104-153 were tested to identify further examples of glycerin and xanthan gum concentrations that form an effective barrier to prevent passage of microorganisms. This data was omitted because this administration does not require a barrier to prevent passage of microorganisms. However, US Patent Publication 2012/0270909 and the provisional application for which this application claims priority benefit include this information.

It should be noted that the addition of an effective antibacterial agent can form a barrier coating effective for surface treatment at lower glycerin and / or xanthan gum concentrations. This is because the antibacterial agent and the barrier coating combine to prevent and / or kill harmful bacteria. In the case of a composition for application to an inanimate surface, it is less important to prevent the passage of microorganisms to the opposite side of the barrier coating since the inanimate surface will not be infected.
(Experimental examples 154-160)

In order to demonstrate the safety of the composition on the mucosal surface, Experimental Examples 154 to 160 were conducted. US Patent Publication No. 2012/0270909 and the provisional application to which this application claims the benefit of priority include this information.
(Experimental Example 161)
<Glycerin-xanthan gum formulation forms a film on human oral mucosa>

In order to determine whether the glycerin-xanthan gum formulation can form a film on the human oral mucosa, the inventors added the formulation of Example 7 using gentian violet (GV) as a marker dye. The added product (750 μL) was sprayed on the oral cavity of human volunteers. After application, the presence or absence of intraoral staining was observed, and an image was taken using a digital camera. As shown in FIG. 21, this formulation stained both cheeks and the dorsal / ventral side of the tongue.
(Experimental examples 162 and 163)
<Time-lapse microscopy in which exposure of microorganisms to coating composition inhibits cell growth>

  To determine the inhibitory activity and duration that the coating composition exhibits activity against microorganisms, a time course analysis was performed on cells exposed to the coating composition compared to untreated bacteria and fungi.

  In Experimental Example 162, S. mutans cells were exposed to Experimental Example 1 for 1 minute, washed to remove residual material, and grown in a Petri dish containing fresh growth medium. The growth of the organism at 37 ° C. was observed for 6 hours and micrographs were taken every 20 minutes during a 6 hour incubation period using a camera connected to a microscope.

  In Experimental Example 163, the same procedure was performed on untreated cells.

  As shown in Figure 22, in contrast to untreated bacteria whose cells reached confluence within 6 hours, the microorganisms treated with the coating composition of Example 7 regrown during the same period after exposure. There wasn't. Similarly, when Candida cells were exposed to the coating composition of Experimental Example 7, growth during the incubation period was completely inhibited (data not shown).

Furthermore, it was confirmed from these results that the coating composition has long-term antibacterial activity.
(Experimental examples 164-166)
<In vivo test: Coating composition (Experimental Example 7) reduces oral microbial burden in humans: short-term activity and long-term activity>
<Short-term activity>

  The activity duration of Experimental Example 7 was measured in healthy individuals by evaluating the effect of single application on the microbial load of oral microorganisms. In Experimental Examples 164 to 166, informed consent was obtained from three healthy persons (healthy mouth aged 18 years or older), and a single application of the composition of Experimental Example 7 was requested on each cheek. Single application was defined as 3 sprays with a volume of 0.25 mL each. Next, swabs were collected from these humans at baseline (pretreatment), 1 hour after treatment, 2 hours after treatment, and 6 hours after treatment. These swabs were cultured on agar plates specific to aerobic or anaerobic organisms, incubated at 37 ° C. for 24-28 hours and counted for CFU. The influence (CFU) of Experimental Example 7 on the microbial load was determined, and the inhibition rate at each post-exposure time point was calculated based on the baseline (0 minute) CFU.

From the results obtained, it was confirmed that the application of Experimental Example 7 consistently reduced the microbial load over a maximum of 6 hours (see FIG. 23A showing the CFU of a representative subject). Treatment with the coating composition resulted in a 69% to 96% reduction in oral microbial load (see FIG. 23B showing a decrease in microbial load in a representative subject).
(Experimental examples 167 to 169)
<Long-term activity>

The activity of the coating composition over 5 days against oral microorganisms was evaluated. In Experimental Example 167-169, 3 healthy subjects were registered, and the single dose of Experimental Example 7 (total of 3 sprays: 0.75 mL) was taken 3 times a day (9am as a guide, noon and 3pm) 3 times) was requested to continue the treatment to be applied for 5 days (typical 5 days per week). Swabs were collected from subjects at the end of each day at baseline (before application on day 1) and at the 5-day study period. Collected swabs were cultured on agar plates and incubated for 24-28 hours at 37 ° C. in a 5% CO ₂ humidified atmosphere and the number of CFU was counted.

The effect of the coating composition of Experimental Example 7 on the microbial load was determined (as the median CFU of 3 subjects), and the inhibition rate at each post-exposure time point was calculated based on the baseline (0 min) CFU. FIG. 24 is a graph showing these results versus CFU versus time (FIG. 24A) and microbial load reduction versus time (FIG. 24B). Experimental Examples 167-169 demonstrate that application of Experimental Example 7 for 5 days resulted in a consistent reduction in microbial load during the 5-day test period (Figure 24A). Treatment with the coating composition of Experimental Example 7 reduced the median microbial load in the oral cavity of the study participants by 65% to 88% (FIG. 24B).
(Experimental examples 170-198)

  In clinical trials, 29 healthy individuals were enrolled after informed consent. Baseline information (age, gender, ethnicity and registration date) was recorded. A mouth pre-examination was performed and the inside of the mouth (cheek) was disinfected with a sterile culture swab. Baseline oral swab samples were cultured to determine the pre-test bacterial load. In Experimental Examples 170-198, each of the 29 participants was given a spray bottle containing the coating composition of Experimental Example 7, sprayed a total volume of 0.75 mL inside their mouth, and then stirred in the mouth for 30 seconds. Instructed to swallow. Two groups of approximately the same number of participants were tested. One group used the experimental coating composition every 2 hours, 3 times a day for 5 days (typical workdays). The other group used the experimental coating composition every 2 hours, 4 times a day for 5 days (typical workdays). There was no significant difference between these two groups. Swabs are collected at the end of days 1, 2, 3, and 5 (8 hours after the initial administration of the coating composition) and cultured on media specific to aerobic and anaerobic bacteria did. The data was divided into aerobic and anaerobic and the number of microorganisms was expressed as a total. FIG. 25 is a graph of total microbial load, and shows the total divided into aerobic and anaerobic counts immediately before treatment and on the fifth day of treatment. FIG. 26 shows a graph of microbial load over five days in oral samples from three representative study participants.

  Overall, in vivo tests have shown that the coating composition has antimicrobial activity against oral microorganisms for both short and long durations, as measured by a decrease in these biological levels.

These data indicated that treatment with the coating composition resulted in a reduction in oral microbial load over 5 days for total aerobic and anaerobic organisms.
(Experimental Examples 199 to 205)
<Identification of an additional moisturizing agent that forms a barrier to prevent microbial invasion>

  In Example 199, various concentrations of various humectants were tested using an in vitro filter insertion base model (see FIG. 27).

  Six compositions were prepared according to Table X based on the mixing procedure used in Experimental Examples 3-8.

  Next, 100 μL of Experimental Examples 199 to 205 were placed in a filter insert (pore size allowing passage of both bacteria and fungi: diameter 0.8 μm) to form a layer. The organism was then overlaid on the layer formed by the test solution. A filter insert containing a layer of test solution and microorganisms was then placed on the surface of the agar plate and incubated at 37 ° C. for 24 hours. After the incubation period, the agar plate was evaluated for growth on the filter insert and in the agar plate. Growth was confirmed on the filter insert but not in the agar medium, indicating that the test solution formed a barrier that prevented the passage of microorganisms. In contrast, a confirmed growth of microorganisms in the filter insert and agar medium indicates that no such barrier was formed.

The results obtained indicate that each xanthan gum-based solution containing the test moisturizer (alone or in combination) formed an intact barrier on the filter insert that prevented the passage of microorganisms to the base agar. It was.
(Experimental examples 206 to 213)

<Determination of solubility limit of xanthan gum>

  To determine the solubility of xanthan gum, xanthan gum was mixed with water at various concentrations and the solubility was observed by monitoring the presence of lumps and the free flow of the mixture. Table XI shows the results and concentrations.

The inventors have discovered that xanthan gum forms a free flowing viscous solution (Table XIII) when mixed at 0.4%. In contrast, mixtures containing 0.45% or 0.5% xanthan gum formed viscous fluids but contained nodules. The degree of lumps increased with increasing xanthan gum concentration (0.6% and 0.7%). At concentrations ≧ 0.8%, the xanthan gum mixture contained a broad mass with a jelly-like consistency and no free flow.
(Experimental example 214)
<Comparison between cationic CPC in coating composition and neutral antibacterial agent in coating composition>

  In Experimental Example 214, the formulation of Experimental Example 7 was prepared except that the neutral agent citral was used instead of CPC. The antibacterial activity against the Streptococcus of the preparation containing CPC (0.1%) or citral (0.5%) was confirmed. To perform these studies, the assay described above in Experimental Examples 48-61 was used.

The obtained results showed that the preparation containing citral showed antibacterial activity (MIC = 12.5%). However, the activity of the formulation containing citral is significantly lower than the formulation containing CPC (MIC = 0.098%).
(Experiment 215)
<Hydrophobic physicochemical test and comparison>

  In Experimental Example 215, the hydrophobicity of the hydrophobic composition was compared with Experimental Example 7 using thin layer chromatography analysis. The components of the hydrophobic composition are as shown in Table XII.

10 μL of Experimental Example 7 and the hydrophobic composition were deposited on a previously prepared TLC plate (to a distance of 2 cm from the lower end). The spots were air dried for 5 minutes and each plate was placed in a TLC chromatography jar containing water as solvent. The TLC system was run until the solvent front reached the top of the plate. The plate was removed and marked with solvent and sample front. The relative front (RF) values of these two samples were calculated by Equation I.
Formula I:
RF = spot moving distance / distance in front of solvent

From the obtained results, the Rf values of the hydrophobic composition and Experimental Example 7 were 0.33 and 0, respectively, indicating that the water-miscible property of the hydrophobic composition was high. In contrast, Experimental Example 7 did not show any mobility in aqueous solvents, demonstrating that the formulation was hydrophobic or not hydrophilic.
(Experiment 216)

Various components described in Table XIII below were mixed in water to prepare a coating composition.
Based on the US homeopathic pharmacopoeia, 5 times the amount of eucalyptol was also included. While this did not affect the test results, it was demonstrated that the composition of this example works in concert with the additional ingredients. Hereinafter, “%” represents all percentages by weight.

(Experimental Examples 217 to 219)

  The coating composition of this example has also been shown to be effective in killing molds that induce allergies. The MIC test was performed on the polystyrene plastic surface.

  In Experimental Example 217, the coating composition of Experimental Example 216 was examined to determine the MIC for Stachybotrys MRL 9740. The MIC of the composition of Experimental Example 7 was 0.06 μg / mL.

  In Experimental Example 218, the coating composition of Experimental Example 216 was examined to determine the MIC for Aspergillus fumigatus 18748. The MIC of the composition of Experimental Example 7 was 0.49 μg / mL.

  In Experimental Example 219, the coating composition of Experimental Example 216 was examined to determine the MIC for Cladosporium. The MIC of the composition of Experimental Example 7 was 0.39 μg / mL.

Since Stachybotrys and Aspergillus fumigatus are organic substances that generate mold, these experimental examples further support embodiments in which a coating composition is applied to the surface to prevent or address mold growth or discoloration.
(Experimental examples 219 to 224)

  In Experimental Examples 219-224, the effect of the coating composition on the MRSA biofilm on the silicone elastomer disk surface was evaluated.

  In Experimental Examples 219 to 221, 0.25 mL of the coating composition of Experimental Example 7 was previously sprayed on three silicone elastomer disks having a diameter of 1 cm and incubated at 37 ° C. for 60 minutes. In Experimental Examples 222-224, silicone elastomer discs were treated as controls by treating with an equivalent amount of phosphate buffered saline (PBS) for 60 minutes and incubated at 37 ° C.

The pretreated disks of Experimental Examples 219 to 224 were each immersed in 4 mL of MRSA suspension (1 × 10 ⁷ cells / mL) and incubated at 37 ° C. for 90 minutes (“adhesion stage”). The disc containing adherent cells was then removed and transferred to a well containing 4 mL brain heart infusion (BHI). These wells were placed on a rocker and incubated at 37 ° C. for 24 hours. Biofilm formation on the disk was evaluated by quantitative culture in BHI agar medium. A scanned image of each well was recorded using a scanner.

  As shown in Table XIV, no biofilm was formed on the disk surface when the pretreatment with the coating composition of Example 7 was performed. FIG. 28 shows images of colony burden in the biofilm formed on PBS treated disks (A, C, E) and disks treated in Example 7 (B, D, F) by MRSA. Show.

(Experimental examples 225 to 246)

The coating composition of Experimental Example 7 was examined to determine the effectiveness against several strains of Bordetella pertussis. In Experimental Examples 225 to 235, the coating composition of Example 7 was placed in a Regan-Lowe Charcoal Agar BBL # 297883 plate and an agar-based assay was performed as a water dilution of 64 μg / mL. Control Examples 236 to 246 were agar plates not containing the coating composition of Example 7. In Experimental Examples 225 to 246, Bordetella pertussis having 5 × 10 ⁴ cells (50 μL) was spotted on the test surface, and each plate was incubated at 37 ° C. for 24 hours. As shown in Table XV, dense growth was observed in the control examples 236 to 246, but no growth was observed in the experimental examples 236 to 246. “4+” in the table indicates significant proliferation.

(Experimental examples 247 to 252)

  The antiviral activity of rhinovirus against ATCC VR-1200 strain was evaluated for the coating composition of Example 7 (at various dilution concentrations).

Human hepatocellular carcinoma (HUH-7) cells were prepared in 24-well plates supplemented with Dulbecco's modified Eagle's medium (DMEM) containing 10% heat-inactivated fetal bovine serum, and L-glutamine (Lglu) and penicillin / Streptomycin (P / S) (all reagents from Gibco (New York) unless otherwise specified) was replenished. All cultured cells were grown to 90% to 100% confluence under conditions of 5% CO ₂ and 37 ° C., and then washed once with OptiMEM (+ P / S + Lglu) before infection.

  In Experimental Examples 247-251, the composition of Experimental Example 7 was mixed with various concentrations (OptiMEM (+ P / S, + Lglu) 400 μL) against CPC working concentrations of 0.005%, 0.01%, 0.015%, 0.02%, and 0.05%. At a dilution concentration of 5%, 10%, 15%, 20%, 50%), and each cell was allowed to stay for 1 hour before inoculation. In Control Example 252, 400 μL of OptiMEM (+ P / S, + Lglu) was applied to the cells and allowed to stay for 1 hour before inoculation.

Subsequently, the cell monolayer was taken out from the diluted solution of Experimental Example 7 or the control OptiMEM, and applied with rhinovirus, and the multiplicity of infection (MOI) was set to 0.1. Cells were incubated with virus for 1 hour at 32.5 ° C. Following this, the inoculum was removed and 500 μL of OptiMEM + P / S + Lglu was placed on the cells. The cells were then grown under conditions of 5% CO ₂ concentration and 32.5 ° C. After 5 days incubation, cell culture supernatant was collected for quantification of rhinovirus loading.

  The rhinovirus titers of the cell culture supernatants of Experimental Examples 247 to 251 were measured by real-time PCR. Compared to Control Example 252, Experimental Example 251 showed a significant decrease in rhinovirus loading, 50% of Example 7. See Table XVI.

(Experimental Examples 253 and 254)

  Experimental Example 253 was prepared with the diluted suspension of Example 7 (CPC concentration 0.05) that is 50% in 500 μL of OptiMEM (+ P / S, + Lglu). Control Example 254 was prepared as a control solution without Experimental Example 7 (500 μL OptiMEM (+ P / S, + Lglu)). Experimental Examples 253 and 254 were applied to the cells disclosed in Experimental Examples 246-252. Pretreatment time intervals were defined as follows: T-1 = 1 hour before infection, T-30 = 30 minutes before infection, T-0 = just before infection.

The cell monolayer was then removed from the suspension of Experimental Example 253 and the control solution of Experimental Example 254. Rhinovirus particles were applied to the treated cell monolayer at a multiplicity of infection (MOI) of 0.1. Cells were incubated with virus for 1 hour at 32.5 ° C. Following this, the inoculum was removed and 500 μL of OptiMEM + P / S + Lglu was placed on the cells. The cells were then grown for 5 days under conditions of 5% CO ₂ concentration and 32.5 ° C. Each cell treated in Experimental Examples 253 and 254 was observed every day to confirm the presence or absence of cytopathic effect. After 5 days incubation, cell culture supernatants were collected for quantification of immunofluorescence and rhinovirus loading.

  FIG. 29 shows a photograph of the cells treated in Experimental Example 253. FIG. 29 (a) shows T-1 (one hour before), FIG. 29 (c) shows T-30 (30 minutes before), and FIG. 29 (b) shows T-0 (just before). None of these photographs showed a cytopathic effect, and healthy cells grew on the entire plate. On the other hand, as shown in FIG. 29 (d), in the untreated control cells of Experimental Example 254, focal rounding, dissociation, and cell death were confirmed. As the determination of cytopathic effect, progression of nest rounding, expansion or contraction of cell size, syncytium formation, development of multinucleated giant cells, and dissociation were determined.

  Immunofluorescence measurement was performed as follows. Virus infected cell monolayers and uninfected controls were washed with sterile PBS. These cells were trypsinized, spotted on wells on slides and fixed with acetone. Each slide was tested by DFA using a FITC-labeled monoclonal antibody. Indirect immunofluorescence assay was performed using Light Diagnostics Pan-Enterovirus Detection Kit (Millipore). This detection kit is well known for showing cross-reactivity with rhinovirus-infected cells. All antibody residence steps were performed at 37 ° C. for 1 hour. After the final washing, the presence or absence of fluorescence in each cell was evaluated at a wavelength of 488 nm.

  FIG. 30 shows an immunofluorescence photograph of the cells pretreated in Experimental Example 253. FIG. 30 (d) shows T-1 (one hour before), FIG. 30 (b) shows T-30 (30 minutes before), and FIG. 30 (c) shows T-0 (just before). The cells treated with Example 253 did not show immunofluorescence for 1 hour 30 minutes. Cells of T-0 (immediately before) treated in Experimental Example 253 showed slight fluorescence. On the other hand, untreated control example 254 showed significant immunofluorescence, suggesting severe viral infection (see FIG. 30 (a)).

  The sample viral load was quantified as follows. Cell culture supernatant was collected and stored at -80 ° C. Nucleic acids were extracted using the QIAamp Viral RNA Kit (QIAGEN (Valencia, Calif.). Random Hexamer Primers (Invitrogen (Carlsbad, Calif.)) To create a cDNA library for each sample. Was performed using M-MLV RT as specified by the manufacturer (Invitrogen, Carlsbad, Calif.) Quantitative analysis was performed on StepOne Plus Taqman Real Time PCR (Applied Biosystems, Branchburg, NJ). , TaqMan Universal PCR Master Mix (Applied Biosystems (Branchburg, NJ)), 2 μL cDNA sample, and primers / probes were used to target the rhinovirus polyprotein gene. Amplified by purified gel (QIAquick, Qiagen (Valencia, Calif.)) Prepared using preconfiguration, shown in Table XVII were quantified. The results using a spectrophotometer (Beckman Coulter, Inc. (Brea, CA).

At 5 days after infection, no rhinovirus amplification was observed at any time of T-1 (1 hour before), T-30 (30 minutes before), or T-0 (immediately before). Untreated (control) cells showed significant amplification (> 10 ⁸ copies / mL), suggesting viral infection.
(Experimental example 255)
<The cetylpyridinium chloride composition exhibits antibacterial activity on an inanimate surface>

  In Experimental Example 255, the activity of a cetylpyridinium chloride spray disinfectant against methicillin-resistant Staphylococcus aureus (MRSA) was evaluated. The antibacterial effect of the surface pre-coated with the composition was analyzed, and the effect of water washing on activity maintenance was analyzed.

  In one embodiment, the coating composition comprising cetylpyridinium chloride has a substantial amount of bactericidal or bacteriostatic activity, such as at least about 35% to about 50%, or about 15% on the stainless steel surface even after being washed with water. Bactericidal or bacteriostatic effects such as ~ 40% were retained after water washing.

  The test CPC composition has the following loading ratio: 93% -97% water, 0.5-1% CPC antibacterial agent, 0.5-1% glycerin, and Cremophor RH-40, copovidone, paraben, and sodium benzoate, etc. The balance of the composition, including any preservatives, none of which is present in an amount greater than about 1%.

The activity of the test CPC composition (CPC _sd ) was assessed by immersing the stainless steel support in MRSA suspension (1 x 10 ⁸ cells) for 15 minutes at 37 ° C. Excess liquid was then drained and the carrier was sprayed with CPC _sd (0.5 mL dose) for 30 seconds, air dried, and incubated overnight in brain heart infusion medium (BHI). An aliquot of the medium was then cultured quantitatively.

To measure the effect on the precoat carrier, the discs were sprayed with CPC _sd (0.50 mL dose), air dried for 2-4 minutes and incubated with MRSA for 15 minutes at 37 ° C. Excess liquid was drained and the support was incubated with BHI overnight before quantitative culture.

The results showed that CPC _sd inhibited the growth of MRSA on the contaminated carrier (CFU count = 0). This was in contrast to a control sample that still had a CFU count of 2.54 × 10 ⁸ . Moreover, pre-coating with CPC _sd prevented bacterial contamination of the carrier (CFU = 0). This is in contrast to a control sample with a CFU count of 3.5 × 10 ⁸ .

  A commercially available disinfectant containing benzalkonium chloride and ethanol was used as a comparator (Bkc-EtOH) and tested similarly. The comparator also showed similar antibacterial activity.

  The effect of water washing on sustained bactericidal activity was examined by washing the precoat carrier with MilliQ (transfer the precoat carrier to 2 mL MilliQ autoclave water and remove in 2-3 seconds), then exposed to MRSA for 15 minutes The number of colony forming units (CFUs) was measured after incubation at 37 ° C. for about 16-24 hours. A commercially available disinfectant containing benzalkonium chloride and ethanol was used as a comparator (Bkc-EtOH) and tested similarly. Cells without disinfectant and cells treated with phosphate buffered saline were used as control samples.

After washing with water and after 16-24 hours, the CPC _sd- treated carrier still showed a 33% bacterial count reduction, in contrast to the comparator-treated carrier, which is a 10% reduction (FIG. 31). Therefore, the test composition CPC _sd was able to maintain 3 times higher activity after the water wash than the comparator.
(Experiment 256)

  A comparison between the composition tested in Example 255 and a common alcohol-based household detergent is presented.

The composition of Experimental Example 255 has the same level of initial antibacterial activity, but is excellent in all safety categories and activities after washing with water.
(Experimental examples 257 to 260)

  Table XIX shows a composition (Formulation 2) that does not contain the gum made in Example 255 and that contains only a low percentage of wetting agent (Formulation 2), and a composition that contains carbohydrate gum ingredients such as those described in Example 7 (Formulation 1). ) To indicate that a comparison has been made.

  In Experimental Examples 257 to 259 shown in FIG. 32, the test was performed by spraying a 0.25 mL dose of Formulation 1 onto a single paper-stock card. After that, another paper stock card was pasted for 1 second and pulled apart. After the second card was applied and pulled apart, the cards were photographed in order to analyze whether the residue on the first card was continuously attached to both cards. As seen in FIG. 32, the composition of Formulation 1 was still attached to the test card at a draw depth of about 0.5 inches. In Formulation 2, following the same procedure and pulling in the same way, no residue was stuck on the second card. Differences in viscosity and film thickness were also seen between the two formulations tested.

  In Experimental Examples 258 to 260 shown in FIG. 33, formulations 1 and 2 at a dose of 0.25 mL were sprayed on a lacquer-coated fiberboard, and the viscosity, layer thickness, and surface area coverage were tested and photographed. In the formulation 1 test, a thicker coating and a narrower surface area were observed compared to the formulation 2 test. It was also clear that the viscosity was higher in the formulation 1 test compared to the formulation 2 test.

Each of Experimental Examples 257 to 260 was performed at room temperature and about 21 ° C.
(Experiment 261)

  To test the bactericidal effect of the coating composition on mammalian skin, including human skin, by testing the antimicrobial activity of the coating composition in a topical pig skin model infected with methicillin-resistant Staphylococcus aureus (MRSA) Experimental Example 261 was conducted. This test is based on the test model reported by Bush et al. In "Pig Skin as Test Substitute for Evaluating Topical Antimicrobial Activity," J. of Clinical Microbiology, p. 343-348 (Sept. 1986).

The collected pig skin was shaved, washed and cut into 3 x 3 cm square pieces. Fit the three square pieces mounted and inoculated with MRSA suspension 0.1mL of 10 ⁵ cells. After the inoculum was dried, one square was treated (sprayed) with about 0.5 mL of the coating composition prepared in Experimental Example 255.

The imprint was produced by inverting the mount holder and pressing the treated and untreated skin against the agar surface. Imprints were made 0 minutes before treatment, 3 minutes, 10 minutes, 30 minutes, 1 hour, 2 hours, and 4 hours after inoculation. FIG. 34 represents a photograph of the agar surface after being made at these time intervals and incubated at 37 ° C. for 24 hours.
(Experimental example 262)

To distribute the composition in a manner that simulates hand application, the test of Example 261 was repeated in the same manner, except that the sprayed skin was applied to another inoculated square piece. Imprints of untreated, sprayed and smeared samples were made 0 minutes before treatment and 3 and 10 minutes after inoculation. FIG. 35 represents a photograph of the agar surface after being made at these time intervals and incubated at 37 ° C. for 24 hours. Even when the imprint was produced after 6 hours, no microbial colonies were observed, indicating sustained efficacy.
(Experimental example 263)

  The test of Experimental Example 262 was repeated in the same manner except that Candida was inoculated into the pig skin sample instead of MRSA. As a result of producing imprints at the same time intervals as in Experimental Example 262, colonies were not formed, and sustained effectiveness was shown.

Claims (23)

A method of treating a body surface with an active agent comprising:
Administering to the body surface a therapeutically effective amount of the composition, the composition forming a barrier coating on the body surface that is effective to maintain contact with the body surface for a duration of at least about 1 hour; A method wherein the composition satisfies the following requirements:
About 0.0001% ≦ C ≦ about 0.4%,
About 0.07% ≦ H ≦ about 70%,
Optionally antibacterial agent A, and a therapeutically effective amount of X;
Or
0% ≦ C ≦ about 0.4%,
About 55% ≦ H ≦ about 70%,
Optionally containing antibacterial agent A, and a therapeutically effective amount of X,
Where all percentages are by weight of the total composition;
C is a carbohydrate gum, H is a wetting agent, and X is an active agent, which has the effect of providing a therapeutic effect on the body.   2. The method of claim 1, wherein the active agent is present in an amount of at least 0.0005% and less than the minimum dose of the active agent that has been approved so far.   The active agent is an antacid, probiotic, vitamin, nutritional supplement, silver, antioxidant, cold or flu symptomatic drug, anti-prion agent, immune stimulant, anti-diarrheal agent, antiemetic, local anesthetic , Topical analgesics, antipruritics (anti-itching agents), antiallergens, topical steroids, decongestants, antitussives, burns or sunburn agents, expectorants, antihistamines, topical NSAIDs, topical salicylates, hair growth agents, erectile dysfunction Therapeutic agent, topical antibiotic, topical wound treatment, antioxidant, hemorrhoid treatment, topical antifungal, anti-acne, scar treatment, psoriasis, dry scalp, anti-dandruff, lice kill The method according to claim 1, wherein the method is selected from the group consisting of one or more selected from the group consisting of a hair care agent, a body odor improving agent, an antiperspirant, and a foot odor improving agent.   2. The method of claim 1, further comprising administering a therapeutically effective amount of the composition to the surface about every 2 to about 12 hours until no therapeutic effect is needed.   The method of claim 1, wherein the composition comprises an antimicrobial agent, wherein the antimicrobial agent is a monoquaternary ammonium compound or a pharmaceutically acceptable salt thereof. 2. The method of claim 1, wherein the step of administering the composition further comprises corresponding to:
a. Identify a contaminated environment in which an individual exists or will be present at high risk (where the contaminated environment is known to be contaminated with harmful viruses, fungi, or bacterial microorganisms or Expected); or b. A contamination event is observed in the environment (where the individual is or will be present in the environment at a high risk state).   The method of claim 1, wherein the composition has a viscosity of less than 500 cps.   The method of claim 1, wherein the composition is a solution.   2. The method of claim 1, wherein the therapeutically effective amount of the composition is non-toxic to human consumption.   The method of claim 1, wherein the body surface is skin. A method for killing microorganisms on the surface of a mammal's skin, comprising:
Applying a composition comprising an antimicrobial agent to the skin surface;
Killing or neutralizing in the coating microorganisms that have contacted on the surface and microorganisms that have come from the surrounding environment and have come into contact after the application step;
Forming a coating layer on the surface;
The composition comprises a wetting agent and an antimicrobial agent;
The antimicrobial agent comprises a monoquaternary ammonium compound or a pharmaceutically acceptable salt thereof;
The method wherein the coating layer has a bactericidal or bacteriostatic effect of at least about 1 hour.   The method of claim 11, wherein the coating composition comprises less than about 50% by weight of a wetting agent and is essentially free of carbohydrate gum. The method of claim 11, wherein the coating composition satisfies the following requirements:
About 0.07% ≦ H ≦ about 10%; and
0.0005% <A,
Where all percentages are by weight of the total composition;
H is the wetting agent and A is the antibacterial agent.   12. A method according to claim 11, wherein the antimicrobial agent is cetylpyridinium chloride.   When the coating layer is applied to a 1 inch diameter area of a single paper stock card at a dose of 0.25 mL, it is completely removed from the second paper stock card placed in contact with the coating layer. The method of claim 11, having a drawing depth of about 0.5 inches or less before being pulled apart.   The microorganism is Candida, Pneumonia, methicillin-resistant Staphylococcus aureus, Streptococcus, Porphyromonas gingivalis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus mutans, Staphylococcus aureus, Yersinia enterocolitica, Acinetobacter baumannii, Streptococcus sanguis, Streptococcus oralis, Streptococcus mitis, Streptococcus salivarius, Streptococcus gordonii, Aggregatebacter actinomycetemcomitans, Fusobacterium nucleatum, Candida albicans, Candida candida Genturata, HIV, EBV, influenza virus, microorganisms causing upper respiratory tract infections, Sentipe Da Periodonthii, Aicella Collodense, Enterobacteria, Fusobacterium nucleatum subspecies Nucleatum, Fusobacterium nucleatum subsp. Polymorph, Fusobacterium nucleatum subsp. Bacteroides melaninogenica, Prevotella Intel Media, Bacteroides lathshay, Solobacteria mulay, Tannerera forcicia (bacteroides forcicia), Treponema denticola, Clostridium difficile, Pertussis, Burkholderia agers , Penicillium, Cladosporium, HPV, cold virus, pneumonia Swine cholera, Escherichia coli (O157: H7), Trichodermatosis, rhinovirus type 39, RS virus, poliovirus type 1, rotavirus Wa strain, influenza A virus, herpes simplex virus type 1 and type 2, and 12. The method of claim 11, wherein the method is selected from the group consisting of hepatitis A virus.   12. The method of claim 11, wherein the antimicrobial component does not include a fatty acid ether or fatty acid ester of a polyhydric alcohol or an alkoxylated derivative thereof.   12. The method of claim 11, wherein the skin surface is a hand and the composition is applied at least daily. Body surface treatment composition comprising:
About 0.0001% ≦ C ≦ about 0.4%,
About 0.07% ≦ H ≦ about 70%,
Optionally antibacterial agent A, and a therapeutically effective amount of X;
Or
0% ≦ C ≦ about 0.4%,
About 55% ≦ H ≦ about 70%,
Optionally containing antibacterial agent A, and a therapeutically effective amount of X,
Where all percentages are by weight of the total composition;
C is a carbohydrate gum, H is a wetting agent, A is an antibacterial agent, and X is an active agent;
The active agents include antacids, probiotics, vitamins, nutritional supplements, silver, antioxidants, cold or influenza symptomatics, anti-prion agents, immunostimulants, anti-diarrheal agents, antiemetics, local anesthetics , Topical analgesics, antipruritics (anti-itching agents), antiallergens, topical steroids, decongestants, antitussives, burns or sunburn agents, expectorants, antihistamines, topical NSAIDs, topical salicylates, hair growth agents, erectile dysfunction Therapeutic agents, topical antibiotics, topical wound treatment agents, antioxidants, hemorrhoid treatment agents, topical antifungal agents, anti-acne agents, scar treatment agents, psoriasis treatment agents, dry scalp treatment agents, anti-dandruff agents, lice killing agents , A hair care agent, a body odor improving agent, an antiperspirant, and a foot odor improving agent.   20. The composition of claim 19, wherein the antimicrobial agent comprises a monoquaternary ammonium compound or a pharmaceutically acceptable salt thereof.   20. A composition according to claim 19, wherein the active agent is a body odor improving agent, an antiperspirant, or both.   20. The composition of claim 19, wherein the composition is a solution and when applied to a 140 U.S. mesh, 95-100% by weight of the composition passes after 30 seconds.   20. A composition according to claim 19, wherein the active agent is eucalyptol.